PMID- 9511927
TI  - Frontiers in research on cystic fibrosis: understanding its molecular and
      chemical basis and relationship to the pathogenesis of the disease.
AB  - In recent years a new family of transport proteins called ABC transporters has
      emerged. One member of this novel family, called CFTR (cystic fibrosis
      transmembrane conductance regulator), has received special attention because of
      its association with the disease cystic fibrosis (CF). This is an inherited
      disorder affecting about 1 in 2000 Caucasians by impairing epithelial ion
      transport, particularly that of chloride. Death may occur in severe cases because
      of chronic lung infections, especially by Pseudomonas aeruginosa, which cause a
      slow decline in pulmonary function. The prospects of ameliorating the symptoms of
      CF and even curing the disease were greatly heightened in 1989 following the
      cloning of the CFTR gene and the discovery that the mutation (deltaF508), which
      causes most cases of CF, is localized within a putative ATP binding/ATP
      hydrolysis domain. The purpose of this introductory review in this minireview
      series is to summarize what we and others have learned during the past eight
      years about the structure and function of the first nucleotide binding domain
      (NBF1 or NBD1) of the CFTR protein and the effect thereon of disease-causing
      mutations. The relationship of these new findings to the pathogenesis of CF is
      also discussed.

PMID- 9511928
TI  - Cystic fibrosis: channel, catalytic, and folding properties of the CFTR protein.
AB  - The identification and characterization of the CFTR gene and protein have
      provided not only a major impetus to the dissection of the molecular
      pathophysiology of cystic fibrosis (CF) but also a new perspective on the
      structure and function of the large superfamily of membrane transport proteins to
      which it belongs. While the mechanism of the active vectorial translocation of
      many hydrophobic substrates by several of these transporters remains nearly as
      perplexing as it has for several decades, considerable insight has been gained
      into the control of the bidirectional permeation of chloride ions through a
      single CFTR channel by the phosphorylation of the R-domain and ATP interactions
      at the two nucleotide binding domains. However, details of these catalytic and
      allosteric mechanisms remain to be elucidated and await the replacement of two
      dimensional conceptualizations with three dimensional structure information.
      Secondary and tertiary structure determination is required both for the
      understanding of the mechanism of action of the molecule and to enable a more
      complete appreciation of the misfolding and misprocessing of mutant CFTR
      molecules. This is the primary cause of the disease in the majority of the
      patients and hence understanding the details of the cotranslational interactions
      with multiple molecular chaperones, the ubiquitin-proteasome pathway and other
      components of the quality control machinery at the endoplasmic reticulum could
      provide a basis for the development of new therapeutic interventions.

PMID- 9511929
TI  - CFTR: domains, structure, and function.
AB  - Mutations in the gene encoding the cystic fibrosis transmembrane conductance
      regulator (CFTR) cause cystic fibrosis (CF) (Collins, 1992). Over 500 naturally
      occurring mutations have been identified in CF gene which are located in all of
      the domains of the protein (Kerem et al., 1990; Mercier et al., 1993; Ghanem et
      al., 1994; Fanen et al., 1992; Ferec et al., 1992; Cutting et al., 1990). Early
      studies by several investigators characterized CFTR as a chloride channel
      (Anderson et al.; 1991b,c; Bear et al., 1991). The complex secondary structure of
      the protein suggested that CFTR might possess other functions in addition to
      being a chloride channel. Studies have established that the CFTR functions not
      only as a chloride channel but is indeed a regulator of sodium channels (Stutts
      et al., 1995), outwardly rectifying chloride channels (ORCC) (Gray et al., 1989;
      Garber et al., 1992; Egan et al., 1992; Hwang et al., 1989; Schwiebert et al.,
      1995) and also the transport of ATP (Schwiebert et al., 1995; Reisin et al.,
      1994). This mini-review deals with the studies which elucidate the functions of
      the various domains of CFTR, namely the transmembrane domains, TMD1 and TMD2, the
      two cytoplasmic nucleotide binding domains, NBD1 and NBD2, and the regulatory, R,
      domain.

PMID- 9511930
TI  - Probing the structural and functional domains of the CFTR chloride channel.
AB  - The cystic fibrosis transmembrane conductance regulator (CFTR) forms an anion
      selective channel involved in epithelial chloride transport. Recent studies have
      provided new insights into the structural determinants of the channel's
      functional properties, such as anion selectivity, single-channel conductance, and
      gating. Using the scanning-cysteine-accessibility method we identified 7 residues
      in the M1 membrane-spanning segment and 11 residues in and flanking the M6
      segment that are exposed on the water-accessible surface of the protein; many of
      these residues may line the ion-conducting pathway. The pattern of the accessible
      residues suggests that these segments have a largely alpha-helical secondary
      structure with one face exposed in the channel lumen. Our results suggest that
      the residues at the cytoplasmic end of the M6 segment loop back into the channel,
      narrowing the lumen, and thereby forming both the major resistance to ion
      movement and the charge-selectivity filter.

PMID- 9511931
TI  - Coupling of ATP hydrolysis with channel gating by purified, reconstituted CFTR.
AB  - The cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride
      channel situated on the apical membrane of epithelial cells. Our recent studies
      of purified, reconstituted CFTR revealed that it also functions as an ATPase and
      that there may be coupling between ATP hydrolysis and channel gating. Both the
      ATP turnover rate and channel gating are slow, in the range of 0.2 to 1 s(-1),
      and both activities are suppressed in a disease-causing mutation situated in a
      putative nucleotide binding motif. Our future studies using purified protein will
      be directed toward understanding the structural basis and mechanism for coupling
      between hydrolysis and channel function.

PMID- 9511932
TI  - Purification, characterization, and expression of CFTR nucleotide-binding
      domains.
AB  - The nucleotide binding domains (NBDs) within CFTR were initially predicted to lie
      in the cell cytoplasm, and to gate anion permeability through a pore that was
      present in membrane spanning alpha helices of the overall polypeptide. Our
      studies designed to characterize CFTR suggest several important features of the
      isolated nucleotide binding domain. NBD-1 appears to bind nucleotides with
      similar affinity to the full-length CFTR protein. In solution, the domain
      contains a high beta sheet content and self-associates into ordered polymers with
      molecular mass greater than 300,000 Daltons. The domain is very lipophilic,
      disrupts liposomes, and readily enters the planar lipid bilayer. Clinically
      important mutations in the domain may disrupt the nucleotide binding capabilities
      of the protein, either through a direct effect on the nucleotide binding site, or
      through effects that influence the overall folding of the domain in vitro.
      Finally, after expression in human epithelial cells (including epithelial cells
      from a CF patient), the first nucleotide binding domain targets the plasma
      membrane even in the absence of other constituents of full-length CFTR and
      mediates anion permeability in these cells.

PMID- 9511933
TI  - Cystic fibrosis: a disease of altered protein folding.
AB  - Cystic fibrosis (CF) is caused by mutations in the gene that encodes the cystic
      fibrosis transmembrane conductance regulator, CFTR. Previously we demonstrated
      that the common delta F508 mutation in the first nucleotide binding domain (NBD1)
      alters the ability of the domain to fold into a functional three-dimensional
      structure, providing a molecular explanation for the observation that the mutant
      CFTR is retained in the endoplasmic reticulum and does not traffic to the apical
      membrane of affected epithelial cells. Notably, when conditions are altered to
      promote folding of the mutant protein, it can assume a functional conformation.
      Correcting the folding defect may have therapeutic benefit for the treatment of
      cystic fibrosis. Here we summarize these results and discuss the implications in
      vitro folding studies have for understanding the pathobiology of CF.

PMID- 9511934
TI  - Strategies for correcting the delta F508 CFTR protein-folding defect.
AB  - Many human diseases arise as a result of mutations within genes encoding
      essential proteins. In many cases, the mutations are not so severe as to render
      the protein biologically inactive. Rather, the mutations oftentimes result in
      only subtle protein-folding abnormalities. In the case of the CFTR protein, a
      mutation leading to the loss of a single amino acid is responsible for the
      diseased state in the majority of individuals with cystic fibrosis. Here the
      newly synthesized mutant CFTR protein, missing a phenylalanine residue at
      position 508 (delta F508 CFTR), is unable to transit from the endoplasmic
      reticulum to the plasma membrane, where it functions as a regulator of chloride
      transport. All of the available evidence indicate that the newly synthesized
      delta F508 CFTR protein adopts a slightly altered conformation and therefore is
      retained at the level of the endoplasmic reticulum, ostensibly by the actions of
      the cellular quality control system. Because the mutant protein is capable of
      functioning as a chloride channel, developing ways to elicit its release out of
      the ER and to the plasma membrane has important clinical implications. Herein, we
      discuss our recent studies showing that the protein-folding defect associated
      with the delta F508 CFTR mutation, as well as a number of other temperature
      sensitive mutations, can be overcome by strategies designed to influence protein
      folding inside the cell. Specifically we show that a number of low-molecular
      weight compounds, all of which are known to stabilize proteins in their native
      conformation, are effective in rescuing the folding and/or processing defects
      associated with different mutations that oftentimes lead to human disease.

PMID- 9511935
TI  - Modeling of nucleotide binding domains of ABC transporter proteins based on a F1
      ATPase/recA topology: structural model of the nucleotide binding domains of the
      cystic fibrosis transmembrane conductance regulator (CFTR).
AB  - Members of the ABC transporter superfamily contain two nucleotide binding
      domains. To date, the three dimensional structure of no member of this super
      family has been elucidated. To gain structural insight, the known structures of
      several other nucleotides binding proteins can be used as a framework for
      modeling these domains. We have modeled both nucleotide binding domains of the
      protein CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) using the two
      similar domains of mitochondrial F1-ATPase. The models obtained, provide useful
      insights into the putative functions of these domains and their possible
      interaction as well as a rationale for the basis of Cystic Fibrosis causing
      mutations. First, the two nucleotide binding domains (folds) of CFTR are each
      predicted to span a 240-250 amino acid sequence rather than the 150-160 amino
      acid sequence originally proposed. Second, the first nucleotide binding fold, is
      predicted to catalyze significant rates of ATP hydrolysis as a catalytic base
      (E504) resides near the y phosphate of ATP. This prediction has been verified
      experimentally [Ko, Y.H., and Pedersen, P.L. (1995) J. Biol. Chem. 268, 24330
      24338], providing support for the model. In contrast, the second nucleotide
      binding fold is predicted at best to be a weak ATPase as the glutamic acid
      residue is replaced with a glutamine. Third, F508, which when deleted causes
      approximately 70% of all cases of cystic fibrosis, is predicted to lie in a cleft
      near the nucleotide binding pocket. All other disease causing mutations within
      the two nucleotide binding domains of CFTR either reside near the Walker A and
      Walker B consensus motifs in the heart of the nucleotide binding pocket, or in
      the C motif which lies outside but near the nucleotide binding pocket. Finally,
      the two nucleotide binding domains of CFTR are predicted to interact, and in one
      of the two predicted orientations, F508 resides near the interface. This is the
      first report where both nucleotide binding domains of an ABC transporter and
      their putative domain-domain interactions have been modeled in three dimensions.
      The methods and the template used in this work can be used to analyze the
      structures and function of the nucleotide binding domains of all other members of
      the ABC transporter super-family.

PMID- 9511936
TI  - Simplified immunophenotypic analysis by laser scanning cytometry.
AB  - Immunophenotypic analysis of hematologic specimens is a useful laboratory adjunct
      to surgical pathology and cytology to confirm or further characterize diagnoses
      of leukemia or lymphoma. Laser scanning cytometry is a new laboratory technology
      that has been adapted to perform immunophenotypic analysis of hematologic
      specimens, with numerous advantages as compared with flow cytometry. In order to
      make full use of the laser scanning cytometer's capabilities, a new method of
      specimen preparation and means of performing the immunofluorescent reactions was
      developed. The technique described in this report, specific only to laser
      scanning cytometry, enables panels of up to 36 different antibodies to be used on
      specimens as small as 50,000 total cells. The laboratory methodology is simple,
      requires 85% less antibody than flow cytometric methods, and allows individual
      cell cytologic morphology to be correlated with objective physical and
      fluorescent measurements on a cell-by-cell basis. Other advantages are described
      in the text. Over the course of nine months in our community hospital, we have
      used this technique clinically to analyze 172 cases of suspected leukemia or
      lymphoma. The method has proven remarkably useful, particularly for extremely
      small specimens such as fine needle aspiration biopsies.

PMID- 9511937
TI  - Platelet fatty acids and peripheral blood lymphocyte subsets in an
      institutionalized elderly population.
AB  - The associations between platelet fatty acids and peripheral blood lymphocyte
      subsets were studied in 78 institutionalized elderly individuals (27 men and 51
      women), aged 67 to 100. Platelet fatty acids were assessed by gas chromatography,
      and peripheral blood lymphocyte subsets were quantitated by immunophenotyping
      using flow cytometry. It was found that women had a higher number of total T
      cells (CD3), T-helper (CD3+4+) cells, and B-cells (CD19). However, no gender
      differences were observed in the percentages of lymphocyte subsets. In elderly
      men, after adjusting for age and fatty acid intake, the platelet concentration of
      omega-3 polyunsaturated fatty acids was positively related to the percentage of
      CD3 and CD3+4+ bearing lymphocytes (rs = 0.59, P < 0.05; and rs = 0.55, P < 0.05,
      respectively), and the concentration of total saturated fatty acids was also
      positively associated with the percentage of B (CD19) cells (rs = 0.50, P <
      0.05). However, similar relationships were not observed in elderly women. No
      significant associations were found between trans fatty acids and any of the
      lymphocyte subsets in the study population. These findings suggest that fatty
      acids may be related to immune function. Any effects may be important in the host
      immune defence, especially in elderly individuals.

PMID- 9511938
TI  - CD26 expression and dipeptidyl peptidase IV activity in an aggressive
      hepatosplenic T-cell lymphoma.
AB  - The transmembrane serine aminopeptidase dipeptidyl peptidase IV (DPP IV) (also
      known as CD26) participates in several immunological functions and has a binding
      affinity for several molecules, including collagen, which may be an integral
      mechanism for T cells to traverse endothelial barriers. Since CD26 is
      phenotypically expressed in certain T-cell malignancies, this study utilized a
      novel four-color cytofluorographic procedure to measure DPP IV enzymatic activity
      concurrently with the expression of other surface markers in an aggressive
      hepatosplenic T-cell lymphoma. Immunophenotypic analysis by flow cytometry
      revealed the tumor to be CD2+, CD3+, CD5-, CD7+, TcR-gamma/delta+, CD4-, CD8+/-,
      CD56+, and CD11c+. The CD26 molecule was also expressed, and DPP IV activity was
      present, with the maximal activity detectable after 10 min of incubation. These
      results represent the initial description of enzymatically active CD26 in a T
      cell malignancy, and raise the possibility that this molecule may be a
      participant in the pathogenetic mechanisms utilized by the neoplastic cells.

PMID- 9511939
TI  - Five-color immunophenotyping plus DNA content analysis by laser scanning
      cytometry.
AB  - Laser scanning cytometry is a new laboratory technology similar to flow cytometry
      but with advantages for certain clinical and research applications. To date,
      laser scanning cytometry has been successfully used to perform three-color
      immunophenotypic analysis of hematologic specimens, single-color
      immunophenotyping plus DNA content analysis of numerous specimen types, and
      automated analysis of fluorescence in situ hybridization specimens. Several other
      interesting applications are also in development. In general, advantages of laser
      scanning cytometry include reduced specimen size requirements, simplified
      methodologies, and the ability to microscopically examine individual cells
      allowing for the direct correlation of cytologic morphology with objective
      fluorescence measurements. In this report, we describe a method which more fully
      takes advantage of the laser scanning cytometer's capabilities for
      immunophenotypic analysis of hematologic specimens. Specifically, we have devised
      a method to increase the number of fluorescent parameters from three to a total
      of six, five representing binding of immunofluorescent antibodies and one for
      stoichiometric measurements of DNA content. As with most laser scanning
      cytometric applications, this technique can be utilized on extremely small
      specimens and enables direct correlation of all of the measured fluorescent
      parameters with light microscopic cytologic morphology.

PMID- 9511940
TI  - Report on the first Latin American Consensus Conference for Flow Cytometric
      Immunophenotyping of Leukemia.
AB  - On October 16, 1996, the first Latin American Consensus Conference for the
      Immunophenotyping of Leukemia took place in Puebla, Mexico, with representatives
      from 10 countries of the region and two external consultants. This document
      summarizes the major conclusions for which scientific consensus was achieved. The
      purpose of disseminating these guidelines to the international community is based
      on the potential interest for other countries with similar social conditions and
      economical restrictions.

PMID- 9511941
TI  - Light scatter pattern of red cell autoagglutination.

PMID- 9511942
TI  - Pharmacotherapy of inpatients with bipolar depression.
AB  - The pharmacotherapy of bipolar depression has not been well studied. Controlled
      studies support the efficacy of some antimanic and antidepressant drugs, but
      these studies usually exclude patients typically seen in nonresearch settings.
      The purpose of this study was to examine the pharmacotherapy of 69 inpatients
      with bipolar depression. More than 90% of the patients received at least one
      antimanic drug, and lithium was used most frequently. Only one-half of the
      patients received antidepressants. Three-quarters of antidepressant-treated
      patients received serotonin reuptake inhibitors or other nontricyclic drugs.
      There were few differences between antidepressant- and non-antidepressant-treated
      patients. Psychotic patients were more likely to receive lithium, neuroleptics,
      and anticholinergics, whereas nonpsychotic patients tended to receive
      anticonvulsants more often. Psychotic patients were also more likely to receive
      polypharmacy. These results suggest that polypharmacy of inpatients with bipolar
      depression is common, and that psychosis is an important variable in the choice
      of pharmacotherapy.

PMID- 9511943
TI  - Assessing sleep in psychiatric inpatients: nurse and patient reports versus wrist
      actigraphy.
AB  - This study was designed to evaluate the conventional techniques of assessing
      sleep, nursing and patient report, of inpatients on a clinical psychiatric unit.
      Nurses assessed sleep/wake status at hourly checks and patients completed a sleep
      diary. For three nights patients wore a wrist actigraph, a portable instrument
      which provides objective data about sleep/wake activity. The nursing and patient
      data obtained were compared with actigraphy data. Nursing staff evaluated sleep
      with satisfactory agreement (76.5% night 1 and 81.6% night 3) that improved over
      the first three nights of hospitalization (p < 0.03). When the nurses' report did
      not agree with the actigraph, they tended to overestimate sleep. Patients tended
      to underestimate their total sleep time and total time awake after sleep onset.
      Time in bed and initial sleep latency were overestimated. There was great
      intersubject variability, making determination of agreement impossible. This data
      suggest that treatment teams on psychiatric units should in general consider
      nursing reports of sleep more accurate than patient self-report. However, since
      nursing staff and patients observe different aspects of sleep, both sources of
      data are important to inpatient treatment teams on clinical units.

PMID- 9511944
TI  - Predictors of long-term outcome in 45 men with antisocial personality disorder.
AB  - We sought to determine variables predictive of outcome in a group of 45 men with
      antisocial personality disorder followed up a mean of 29 years following
      hospitalization. Based on personal interviews, interviews with informants, and
      medical and legal records, sufficient information was available to rate the
      global outcome in 45 men. The Global Assessment Scale (GAS) was also used to
      measure functioning in 44 men at intake and follow-up. Twenty-six (57.8%) were
      rated as having "any improvement." Univariate analysis showed men experiencing
      improvement were more likely to have high GAS scores at intake, were not
      currently alcoholic, were older, and were followed over a longer period of time.
      Low GAS scores at intake and the interaction between the GAS score at intake and
      current alcoholism independently predicted poor outcome on regression analysis. A
      low GAS score at intake and shorter follow-up also independently predicted poor
      outcome, even though stepwise regression revealed the strongest single predictor
      to be the interaction between the initial GAS score and age at follow-up. In
      summary, long-term outcome in antisocial males is associated with an initial
      level of severity, alcohol consumption at follow-up, and both age at follow-up
      and length of follow-up. Initial severity best predicts outcome among men not
      currently alcoholic who have been followed over a long period of time.

PMID- 9511945
TI  - The duration of delirium in medical and postoperative patients referred for
      psychiatric consultation.
AB  - OBJECTIVE: We wished to produce a complete frequency distribution of the duration
      of delirium in a large number of patients referred for psychiatric consultation,
      plot the data as a "survivorship" curve for delirium, and examine differences
      between postoperative and medical patients and between demented and nondemented
      patients. METHODS: The senior author entered into the study 94 consecutive
      patients referred to him because of confusion and agitation and diagnosed by him
      as having a delirium and followed them closely throughout their hospital course.
      Patients were telephoned for follow-up after discharge. RESULTS: The rate of
      disappearance of delirium appeared log linear for approximately 2 weeks, but rate
      of resolution for medical patients was slower than for postoperative patients.
      The mean and median duration of delirium for medical patients were, respectively,
      13.2 and 8 days, and for postoperative patients, 7.6 days and 6 days. Combined
      mortality over 3 1/2 years was 46.8%. Demented patients had longer average
      durations of delirium than nondemented patients, but differences were not
      statistically significant because of large variance. CONCLUSIONS: In a large
      heterogeneous group of hospitalized patients referred for psychiatric
      consultation, the mean duration of delirium was shorter for postoperative than
      for medical patients. The difference could not be explained by different criteria
      for referral. Mortality was high for both groups.

PMID- 9511947
TI  - Depression subtyping in PTSD patients.
AB  - A Structured Clinical Interview for the DSM-IV (SCID) and psychological testing
      were administered to 260 combat veterans in order to investigate the relationship
      between symptoms of post-traumatic stress disorder (PTSD) and melancholic
      features of depression. Sixty-seven percent of PTSD patients experiencing
      comorbid major depression acknowledged symptoms indicative of a melancholic
      depression subtype. Correlational and regression analyses show that the presence
      of melancholic features is related to severity of emotional-numbing experienced
      by the PTSD patients. These results suggest PTSD patients are likely to
      experience depressive episodes phenomenologically similar to melancholic
      depression. It is likely that acknowledgment of melancholic symptoms is due to
      (a) the inclusion of guilt as a melancholic feature, and (b) the similarities
      between emotional numbing symptoms and other melancholic features.

PMID- 9511946
TI  - The effects of clozapine on negative symptoms in patients with schizophrenia with
      minimal positive symptoms.
AB  - The effectiveness of clozapine in the treatment of the negative symptoms of
      schizophrenia remains controversial, as improvements in negative symptoms are
      invariably accompanied by improvements in positive symptoms and neurological side
      effects. We examined the effectiveness of treatment with clozapine on negative
      symptoms in a cohort of patients with minimal positive symptoms. Improvements in
      positive and negative symptoms were measured by BPRS ratings in a subgroup of
      schizophrenic patients (n=17, from a state hospital cohort of 75) with minimal
      positive symptoms, who had received clozapine for 6 months. In this subgroup,
      significant improvements were noted by a composite score on the three negative
      symptom items of emotional withdrawal, blunted affect, and motor retardation.
      Positive and depressive symptoms remained unchanged. The remaining cohort (n=58)
      showed improvements in overall psychopathology including positive, negative, and
      depressive symptoms. Interestingly, nearly 50% of each group were discharged from
      the hospital. These findings suggest that clozapine may be beneficial in the
      treatment of core negative symptoms, even in the absence of other improvements in
      psychopathology. This effect of clozapine may be a function of its unique
      pharmacological profile.

PMID- 9511948
TI  - Bupropion treatment of serotonin reuptake antidepressant-associated sexual
      dysfunction.
AB  - Serotonin reuptake inhibitor (SRI)-induced sexual dysfunction is common, and a
      number of pharmacologic adjunctive strategies have been employed to treat this
      vexing problem. This open label study tested the efficacy of adjunctive bupropion
      across several measures of sexual function. Patients taking SRIs for various mood
      or anxiety disorders who reported prospective decline in sexual function after at
      least 2 months on SRIs were offered treatment with bupropion, 75 mg/day. Eight
      patients were treated, and sexual function was measured by use of a visual analog
      scale at 1 month of treatment. Four of eight patients experienced marked
      improvement in sexual dysfunction following adjunctive bupropion treatment.
      Bupropion may be a pharmacologic option for treating SRI-associated sexual
      dysfunction, though controlled clinical trials are needed.

PMID- 9511949
TI  - Catatonia in an adolescent with Prader-Willi Syndrome.
AB  - Catatonia in children and adolescents has received little research attention.
      Treatment and course of catatonia in an adolescent patient with Prader-Willi
      Syndrome are presented. Clinical features of a small series of published case
      reports of catatonia in children and adolescents are reported. The association
      between catatonia, Prader-Willi Syndrome, and other neurodevelopmental disorders
      is discussed.

PMID- 9511950
TI  - Sertraline in diabetic neuropathy: preliminary results.
AB  - Previous research has shown that antidepressants have been useful in the
      treatment of pain, particularly diabetic neuropathy. This study was an initial
      open investigation into the use of sertraline in diabetic neuropathy. Eight
      patients with diabetic neuropathy but not depression were treated with increasing
      doses of sertraline to a maximum of 150 mg/day for 8 weeks. Sertraline treatment
      led to significant reductions in mean visual analog scale (VAS) ratings, e.g.,
      pain from 71.2 to 23.1 (t = 3.74, p < .01) and paresthesias from 53.8 to 15.0 (t
      = 4.15, p < .01). Baseline platelet serotonin (5HT) content also correlated
      significantly with improvement in pain (r = 0.70,p =. 05). Plasma sertraline
      (SRT) correlated with improvement in paresthesias (r = 0.70). CONCLUSION: This
      preliminary result indicates the potential application of sertraline to treatment
      of diabetic neuropathy. A replication is now underway.

PMID- 9511951
TI  - Adjunctive use of olanzapine in mood disorders: five case reports.
AB  - Olanzapine has emerged as an atypical antipsychotic with few side effects and
      potentially superior efficacy in the treatment of schizophrenia. To our knowledge
      there have been few published reports of olanzapine in the treatment of mood
      disorders. We report on the adjunctive use of this medication in three subjects
      with mania and two with depression. Response occurred rapidly and patients
      tolerated the medication. Olanzapine offers promise in the treatment of mood
      disorders.

PMID- 9511952
TI  - Self-reported suicide attempts by adolescents.
AB  - A thorough medical literature review of adolescent self-reported suicide attempts
      focused on comparing the following: (1) the prevalence of attempts in anonymous
      vs. face-to-face surveys; (2) the prevalence rates in the United States and
      Canada vs. those reported elsewhere; and (3) the prevalence of attempt findings
      vs. self-harm behavior in anonymous surveys. The major findings were: (1) 29
      anonymous self-report questionnaire studies from nine countries revealed that a
      median of 7-10% of adolescent students acknowledged having made one or more
      suicide attempts; (2) seven structured interview studies revealed a 3-4% lifetime
      prevalence of attempted suicide by adolescents; (3) self-report questionnaire
      responses failed to reveal any overlap between deliberate self-harm behavior and
      suicide attempts; (4) nonanonymous studies had an unusually high rate of refusal.
      Thus, self-reported suicide attempts are surprisingly frequent in adolescence and
      are reported two to three times more often under conditions of anonymity.
      Furthermore, youths report self-harm behavior as distinct from suicide attempts.

PMID- 9511953
TI  - Structural and energetic aspects of protein-protein recognition.
AB  - Specific recognition between proteins plays a crucial role in a great number of
      vital processes. In this review different types of protein-protein complexes are
      analyzed on the basis of their three-dimensional structures which became
      available in recent years. The complexes which are analyzed include: those
      resulting from different types of recognition between proteinase and protein
      inhibitor (canonical inhibitors of serine proteinases, hirudin, inhibitors of
      cysteine proteinases, carboxypeptidase inhibitor), barnase-barstar, human growth
      hormone-receptor and antibody-antigen. It seems obvious that specific and strong
      protein-protein recognition is achieved in many different ways. To further
      explore this question, the structural information was analyzed together with
      kinetic and thermodynamic data available for the respective complexes. It appears
      that the energy and rates of specific recognition of proteins are influenced by
      many different factors, including: area of interacting surfaces; complementarity
      of shapes, charges and hydrogen bonds; water structure at the interface;
      conformational changes; additivity and cooperativity of individual interactions,
      steric effects and various (conformational, hydration) entropy changes.

PMID- 9511954
TI  - High coordination lattice models of protein structure, dynamics and
      thermodynamics.
AB  - A high coordination lattice discretization of protein conformational space is
      described. The model allows discrete representation of polypeptide chains of
      globular proteins and small macromolecular assemblies with an accuracy comparable
      to the accuracy of crystallographic structures. Knowledge based force field, that
      consists of sequence specific short range interactions, cooperative model of
      hydrogen bond network and tertiary one body, two body and multibody interactions,
      is outlined and discussed. A model of stochastic dynamics for these protein
      models is also described. The proposed method enables moderate resolution
      tertiary structure prediction of simple and small globular proteins. Its
      applicability in structure prediction increases significantly when evolutionary
      information is exploited or/and when sparse experimental data are available. The
      model responds correctly to sequence mutations and could be used at early stages
      of a computer aided protein design and protein redesign. Computational speed,
      associated with the discrete structure of the model, enables studies of the long
      time dynamics of polypeptides and proteins and quite detailed theoretical studies
      of thermodynamics of nontrivial protein models.

PMID- 9511955
TI  - Helix-coil transition theories. Are they correct?
AB  - Principles of contemporary theoretical description of alpha-helix formation by
      polypeptide chains in water solution are shortly presented and critically
      discussed. The theory treats the unfolded state of a peptide as "random coil"--an
      ideal conformation quite distant from reality. We suggest that for this reason
      the helix propagation parameters of amino-acid residues, determined using series
      of model peptides with different sequential patterns, are not the same.
      Interpretation of the so called "nucleation parameter" is erroneous. In fact, it
      is not determined by the helix nucleation process but rather by a specific
      situation of residues at the helix N- and C-termini, and it strongly depends on
      solvation of their NH and CO groups, respectively. Consequently, helical segments
      with terminal sequences dominated by residues with strongly hydrophobic, bulky
      side chains can be very unstable. We postulate that an unexpectedly high
      stability of very short, pre-nucleated helices studied by us arises from a "helix
      end separation effect": separated helix termini are better solvated than when
      they overlap each other. Because of this effect, helix initiation may be much
      more difficult than predicted by the theoretical "helix nucleation parameters".

PMID- 9511956
TI  - Disulfide bonds in protein folding studies: friends or foes?
AB  - The studies on protein folding pathways utilizing disulfide bonds as reporter
      groups in several protein model systems are reviewed. Implications for a general
      mechanism of protein folding are discussed. An updated folding pathway for bovine
      pancreatic trypsin inhibitor (BPTI) based on recent data is proposed.

PMID- 9511957
TI  - Elucidation of neurophysin/bioligand interactions from molecular modeling.
AB  - This is a review of our recent modeling work aimed at: (i) development and
      assessment of techniques for reliable refinement of low-resolution protein
      structures and (ii) using these techniques, at solving specific problems
      pertinent to neurophysin-bioligand interactions. Neurophysins I and II (NPI and
      NPII) serve in the neurosecretory granules of the posterior pituitary as carrier
      proteins for the neurophyseal hormones oxytocin (OT) and vasopressin (VP),
      respectively, until the latter are released into blood. NPs are homologous two
      domain, sulphur rich small proteins (93-95 residues, 7 disulphide bridges per
      monomer), capable of being aggregated. The C2 symmetrical NPI2 and NPII2
      homodimers, and the (NPI/OT)2 and (NPII/VP)2 heterotetramers, all believed to be
      the smallest functional units, were modeled using low-resolution structure
      information, i.e. the C alpha-carbon coordinates of the homologous NPII/dipeptide
      complex as a template. The all-atom representations of the models were obtained
      using the SYBYL suite of programs (by Tripos, Inc.). Subsequently, they were
      relaxed, using a constrained simulated annealing (CSA) protocol, and submitted to
      about 100 ps molecular dynamics (MD) in water, using the AMBER 4.1 force field.
      The (NPI/OT)2 and (NPII/VP)2 structures, averaged after the last 20 ps of MD,
      were remarkably similar to those recently reported either for NPII/dipeptide or
      NPII/oxytocin complex in the solid state (Chen et al., 1991, Proc. Natl. Acad.
      Sci., U.S.A. 88, 4240-4244; Rose et al., 1996, Nature Struct. Biol. 3, 163-169).
      The results indicate that the 3(10) helices (terminating the amino domains) and
      the carboxyl domains are more mobile than the remainder of the NP monomers. The
      hormones become anchored by residues 1-3 and 6 to the host, leaving residues 4-5
      and 7-9 exposed on the surface and free to move. A cluster of attractive
      interactions, extending from the ligand binding site, Tyr-24-Ile-26 of unit 1(2),
      to the inter-monomer interface Val-36 of unit 1(2), Cys-79 and Ile-72 of unit
      2(1), is clearly seen. We suggest that both these interactions as well as the
      increased mobility of the 3(10) helix and the carboxyl domain may contribute to
      the allosteric communication between the ligand and the unit1-unit2 interface.

PMID- 9511958
TI  - The impact of the amino-acid sequence on the specificity of copper(II)
      interactions with peptides having nonco-ordinating side-chains.
AB  - The review presents specific interactions that occur in complexes of Cu(II) ions
      with peptides composed only of amino acids with nonco-ordinating side chains.
      Three classes of such peptides are discussed. The first type (NSFRY analogues) is
      characterised by the presence of a specific combination of bulky and aromatic
      residues, leading to a formation of multiple weak interactions around Cu(II) that
      result in an extremely high stability of complexes. The second class is composed
      of complexes of vasopressins and oxytocins, achieving superstability through a
      pre-conformation in the peptide molecule. The third group are oligopeptides
      containing one or two proline residues. These peptides form exotic macrochelate
      loops with Cu(II) in a result of the break-point effect of Pro residues.
      Particular emphasis in the review was given to stability constants of complexes,
      compared to oligoglycine or oligoalanine peptides.

PMID- 9511959
TI  - Fluorescence resonance energy transfer in studies of inter-chromophoric distances
      in biomolecules.
AB  - Fluorescence resonance energy transfer (FRET) is a technique widely used in
      studies of interchromophoric distances in biomolecules such as peptides, proteins
      and nucleic acids. FRET is especially useful in determination of conformational
      changes caused by a solvent, presence of denaturing agents, diffusion and other
      external factors. Precision of interchromophoric distances obtained using the
      FRET technique is comparable with that of low-resolution X-ray diffraction and
      NMR data. Comparison of FRET results with the crystal structure for several
      proteins is reviewed. Moreover, the effect of the orientation factor kappa2 value
      on FRET results and determinants of kappa2 are discussed.

PMID- 9511960
TI  - Why a "benign" mutation kills enzyme activity. Structure-based analysis of the
      A176V mutant of Saccharomyces cerevisiae L-asparaginase I.
AB  - A conservative and apparently harmless A176V mutation in intracellular S.
      cerevisiae L-asparaginase (ScerAI) completely abolishes the enzyme activity.
      Sequence and structural comparisons with type II bacterial L-asparaginases show
      that the mutated residue is in a very conservative region and plays a vital role
      in the cohesion of functional tetramers of these enzymes through participation in
      side-chain...main-chain (Ser) Oy...O (Ala) hydrogen bonds across the tetramer
      interface. The fact that bacterial L-asparaginases of type I show less
      conservation in this region suggests that they may have different quaternary
      structure while adopting the subunit fold and intimate dimer architecture of type
      II enzymes. A comparison of all available sequences of microbial L-asparaginases
      confirms that separate intra- and extra-cellular enzymes evolved in prokaryotes
      and eukaryotes independently. However, an analysis of the available complete
      genome sequences reveals a surprising fact that Haemophilus influenzae possesses
      only a type II asparaginase while the archaebacterium Methanococcus jannaschii
      has a type I gene, but not a type II.

PMID- 9511961
TI  - Crystal structure of rat transthyretin at 2.5 A resolution: first report on a
      unique tetrameric structure.
AB  - The first observation of a unique tetrameric molecular structure of transthyretin
      from rat (rTTR, prealbumin) is reported. The structure has been determined by X
      ray diffraction using molecular replacement and the structure of human
      transthyretin (hTTR) as a starting model. Crystals of native rat transthyretin
      are tetragonal, space group P4(3)2(1)2, and have four independent monomers in the
      asymmetric unit of the crystal lattice. Data were collected to 2.5 A resolution
      and the structure has been refined to R = 18.9% for 13584 data points between 8
      2.5 A resolution. Like hTTR, the rat protein is also a 54000 Da tetramer with
      four identical polypeptide chains of 127 amino-acid residues. Of the 22 amino
      acid residues which are different in the human and rat TTR sequences, none are in
      the thyroxine binding domain. Analysis of these data reveal that the tertiary
      structure of rTTR is similar to that of hTTR with only small differences in the
      flexible loop regions on the surface of the protein. As a result of local changes
      in flexible loop regions near residues 30-41, 60-65 and 102-104, the structure of
      rTTR monomers is more compact than that of the corresponding hTTR monomers. The
      loop between residues 30-41 is bound closer to the monomer core in the former as
      compared with the latter structure and there is a wider opening of the space
      formed between these loops at two adjacent monomeric subunits. These
      conformational changes do not affect the interfaces between the monomeric
      subunits and are not transmitted to the thyroxine binding site so that its
      topology remains not altered.

PMID- 9511962
TI  - The determination of thymopoietin conformation based on X-ray structure of a
      discontinuous thymopoietin-like motif of G-actin.
AB  - The biologically active conformation of thymopoietin, based on X-ray data
      reported for discontinuous thymopoietin-like motif of G-actin, is proposed. The
      conformation is compared with that resulting from the prediction made by the
      method of Chou & Fasman (Annu. Rev. Biochem. 47, 251-276, 1978) and Rost & Sander
      (Methods Enzymol. 266, 525-539, 1996).

PMID- 9511963
TI  - Design of a knowledge-based force field for off-lattice simulations of protein
      structure.
AB  - Prediction of protein structure from amino-acid sequence still continues to be an
      unsolved problem of theoretical molecular biology. One approach to solve it is to
      construct an appropriate (free) energy function that recognizes the native
      structures of some selected proteins (whose native structures are known) as the
      ones distinctively lowest in (free) energy and then to carry out a search of the
      lowest-energy structure of a new protein. In order to reduce the complexity of
      the problem and the cost of energy evaluation, the so-called united-residue
      representation of the polypeptide chain is often applied, in which each amino
      acid residue is represented by only a few interaction sites. Once the global
      energy minimum of the simplified chain has been found, the all-atom structure can
      easily and reliably be constructed. The search of the lowest-energy structure is
      usually carried out by means of Monte Carlo methods, though use of more efficient
      global-optimization methods, especially those of deformation of original energy
      surface is potentially promising. Monte Carlo search of the conformational space
      can be accelerated greatly, if the chain is superposed on a discrete lattice (the
      on-lattice approach). On the other hand, the on-lattice approach prohibits the
      use of many efficient global-optimization methods, because they require both
      energy and its space derivatives. The on-lattice methods in which the chain is
      embedded in the continuous 3D space are, therefore, also worth developing. In
      this paper we summarize the work on the design and implementation of an off
      lattice united-residue force field that is underway in our group, in cooperation
      with Professor HA. Scheraga of Cornell University, U.S.A.

PMID- 9511964
TI  - Energy minimization of globular proteins with solvent effects included.
      Comparison of empirical solvation energy terms and explicit water treatment.
AB  - The effect of an empirical solvation energy term on energy minimization of
      ribonuclease T1 was established using different sets of Atomic Solvation
      Parameters. The results are compared to minimization in vacuo and in a 10 A water
      shell. The best solvent model as judged from the comparison to the crystal
      structure was an empirical solvation potential derived from free energies of
      transfer of amino-acid side-chain analogues from vapour to water. The use of this
      model causes, however, energy and gradient oscillations, which make it
      inapplicable with standard protocols of molecular dynamics simulations. The
      empirical solvation model which was found by other authors (von Freyberg et al.,
      1993, J. Mol. Biol. 233, 275-292) to give good results in the NMR structure
      refinement led to distortions of the ribonuclease native structure. The model
      based on statistical analysis of crystal structures did not perform better than
      minimization in vacuo.

PMID- 9511965
TI  - Modelling of active forms of protein kinases: p38--a case study.
AB  - An active form of p38 protein kinase, belonging to the mitogen-activated protein
      kinases subfamily, has been designed based on crystallographically known
      structures of two other kinases, an active form of protein kinase A (PKA) and an
      inactive form of extracellular signal-regulated kinase 2 (ERK2). The modelling
      procedure is described. Its general scheme can also be applied to other kinases.
      The structure of the active forms of p38 and PKA is very similar in the region
      which binds the substrate. The ATP-binding mode is very similar in the active
      forms of all the three studied kinases. Models of the active forms allow for
      further studies on transphosphorylation processes at the molecular level, and
      modelling of inhibitors competitive with ATP and/or substrates.

PMID- 9511966
TI  - Expression of Lupinus luteus cDNA coding for PR10 protein in Escherichia coli:
      purification of the recombinant protein for structural and functional studies.
AB  - The cDNA clones coding for two pathogenesis-related protein homologues of PR10
      class, LlPR10.1A and LlPR10.1B, were identified in yellow lupin expression
      library of uninfected roots. The contribution of PR10 proteins to the overall
      mechanism of plant defence still remains unknown. In order to elucidate the
      structure and function of lupin PR10.1A protein, a substantial quantity of the
      protein was produced in an E. coli expression system using plasmids of pET
      series: pET-3a and pET-15b, carrying the T7 promoter. Both plasmids with
      subcloned Llpr10.1a gene were overexpressed in E. coli, strain BL21(DE3)pLysS.
      The recombinant LlPR10.1A protein, overproduced in bacterial cells transformed
      with the pET-3a/Llpr10.1a plasmid, was purified to homogeneity from the insoluble
      "inclusion bodies" by ammonium sulphate fractionation and two sequential
      chromatographic steps: ion-exchange chromatography on DE 52 cellulose followed by
      size exclusion chromatography on Superdex 75 FPLC column. The (His)6 LlPR10.1A
      protein overproduced in E. coli cells harbouring the pET-15b/Llpr10.1a plasmid
      was purified by chromatography on Ni2+-charged His. Bind Resin. Western blot
      analysis with rabbit serum containing anti-LlPR10.1AN antibody revealed identical
      immunochemical properties of the two recombinant polypeptides and native
      LlPR10.1A protein. The recombinant protein produced in pET-3a plasmid was
      renatured from its insoluble form, concentrated up to 22 mg/ml and submitted to
      crystallisation. However, the LlPR10.1A protein expressed in pET-15b plasmid
      precipitated from the solution when at a higher concentration (10 mg/ml). This
      preparation was used at a lower concentration as an antigen for the preparation
      of polyclonal antibodies for immunochemical studies.

PMID- 9511967
TI  - Maize TF IIIA--the first transcription factor IIIA from monocotyledons.
      Purification and properties.
AB  - Purification and properties of transcription factor IIIA (TF IIIA) from maize
      pollen (Zea mays L.) are presented for the first time. The purified protein has a
      molecular mass of about 35 kDa and exhibits binding affinity toward both 5S rRNA
      and 5S rRNA gene. It also facilitates transcription of the 5S rRNA gene in a HeLa
      cell extract.

PMID- 9511969
TI  - Crystallization and preliminary crystallographic studies of a new crystal form of
      papain from Carica papaya.
AB  - A new crystal form of papain from the latex of Carica papaya, complexed with an
      inhibitor (Z-Arg-Leu-Val-Gly-CHN2) was obtained by the vapor-diffusion method
      using a methanol/ethanol mixture as a precipitant. The slat-like crystals are
      monoclinic, space group P2(1), with unit cell parameters a = 42.6 A, b = 49.8 A,
      c = 50.5 A, A = 111.9 degrees, and contain one molecule in the asymmetric unit.
      The crystals are stable in the X-ray beam and diffract beyond 1.8 A. A molecular
      model has been placed in the unit cell by molecular replacement.

PMID- 9511968
TI  - Interaction of HIV Tat model peptides with tRNA and 5S rRNA.
AB  - New data are presented on the interaction of model synthetic peptides containing
      an arginine-rich region of human immunodeficiency virus (HIV-Tat), with native
      RNA molecules: tRNA(Phe) of Saccharomyces cerevisiae and 5S rRNA from Lupinus
      luteus. Both RNA species form complexes with the Tat1 (GRKKRRQRRRA) and Tat2
      (GRKKRRQRRRAPQDSQTHQASLSKQPA) peptides, as shown by electrophoretic gel shift and
      RNase footprint assays, and CD measurements. The nucleotide sequence UGGG located
      in the dihydrouridine loop of tRNAPhe as well as in the loop D of 5S rRNA is
      specifically protected against RNases. Our data indicate direct interactions of
      guanine of RNA moieties with arginine residues. These interactions seem similar
      to those observed in DNA-protein complexes, but different from those previously
      observed in the TAR RNA-Tat complexes.

PMID- 9511970
TI  - Conformations, orientations and time scales characterising
      dimyristoylphosphatidylcholine bilayer membrane. Molecular dynamics simulation
      studies.
AB  - The results of molecular dynamics simulation of fully hydrated
      dimyristoylphosphatidylcholine (DMPC) bilayer membrane in the liquid-crystalline
      phase are presented. They show that the probability of a gauche conformation
      varies periodically along the chain with only a slight increase towards the end
      of the chain. However, the frequency of transition between conformations
      increases, due to a decrease in the lifetime of the trans conformation, along the
      chain. The average lifetimes for trans conformations are in the range of 1-2 x
      10(-10) s and for gauche conformations in the range of 4-7 x 10(-11) s. The alpha
      chain of the DMPC head group has mainly an extended conformation, due to
      predominantly trans conformation of alpha5 torsion. The rotational correlation
      time for the P-N vector is 3.7 ns. The C2-C1-O11-P fragment of the DMPC head
      group (theta1, alpha1, alpha2 torsions) is rigid while the P-O12-C11-C12 fragment
      (alpha3, alpha4, alpha5 torsions) is flexible. The lateral diffusion coefficient
      for DMPC self-diffusion in the membrane is 2 x 10(-7) cm2/s; the rate of
      transverse diffusion is the same. Large differences in the calculated rotational
      correlation times for the alpha-, beta-, gamma-chains and for the O21-C1 vector
      indicate that in the liquid-crystalline bilayer each segment of the DMPC molecule
      exhibits its own rotational freedom, in addition to its internal flexibility
      resulting from rotational isomerism. The results obtained in these calculations,
      although in general agreement with some experimental data, shed new light on the
      dynamical behaviour of phosphatidylcholine molecules in the bilayer membrane in
      the liquid-crystalline phase.

PMID- 9511971
TI  - Prenatal diagnosis of Walker-Warburg syndrome in three sibs.
AB  - Walker-Warburg syndrome (WWS) is an autosomal recessive condition characterized
      by diffuse neurodysplasia, resulting in brain and eye abnormalities. We report on
      3 prenatally diagnosed cases of this syndrome born to a consanguineous couple. An
      ultrasonographic examination showed hydrocephalus at the 27th week of the first
      pregnancy. Amniocentesis documented a normal male karyotype. The couple opted for
      termination of the pregnancy but declined an autopsy. Seven months later,
      hydrocephalus was observed at 20 weeks of the second pregnancy. Termination of
      pregnancy was performed at the 22nd week. Autopsy of this male fetus showed
      dilated ventricles, thin cortex, and type II lissencephaly with microscopic
      evidence of chaotic architecture. Eye examination showed retinal dysplasia.
      Notwithstanding the lack of demonstrable muscle change, the diagnosis of Walker
      Warburg syndrome was made. Ten months later, hydrocephalus was discovered in the
      third fetus, a female, at 13 weeks of gestation. Termination of pregnancy was
      performed at 20 weeks. At autopsy, brain, eye, and muscular findings were similar
      to those of the previous case. In addition, cystic changes and a stenosis of the
      pyelo-ureteral junction were found in the right kidney. Type II lissencephaly and
      retinal dysplasia are characteristic of WWS. Muscular dystrophy has been pointed
      out as an additional abnormality in postnatal cases. By contrast, the lack of
      demonstrable muscle changes in the fetal period must be emphasized. Those cases
      illustrate practical problems in the ultrasound and pathologic diagnosis of WWS
      in the fetal period.

PMID- 9511972
TI  - Attitudes of young adults to prenatal screening and genetic correction for human
      attributes and psychiatric conditions.
AB  - With recent advances in DNA technology, questions have arisen as to how this
      technology should be appropriately used. In this article, results obtained from a
      survey designed to elicit attitudes of college students to prenatal testing and
      gene therapy for human attributes and psychiatric conditions are reported. The
      eleven hypothetical disease phenotypes included schizophrenia, alcoholism,
      tendency toward violent behavior, attention deficit/hyperactivity disorder,
      depression requiring medical treatment, obesity, involvement in "dangerous"
      sports activities, homosexuality, borderline normal IQ (80-100), proportional
      short stature, and inability to detect perfect pitch. Most students supported
      prenatal genetic testing for psychiatric disorders and behavior that might result
      in harm to others (i.e., tendency towards violent behavior) and found prenatal
      genetic testing for human attributes less desirable. However, the lack of
      unilateral agreement or disagreement toward any one condition or attribute
      suggests the potential difficulties ahead in the quest for guidelines for the
      application of new technologies available to manipulate the human genome.

PMID- 9511973
TI  - Frequency of Y chromosomal material in Mexican patients with Ullrich-Turner
      syndrome.
AB  - Cytogenetic studies have shown that 40-60% of patients with Ullrich-Turner
      syndrome (UTS) are 45,X, whereas the rest have structural aberrations of the X
      chromosome or mosaicism with a second cell line containing a structurally normal
      or abnormal X or Y chromosome. However, molecular analysis has demonstrated a
      higher proportion of mosaicism, and studies in different populations have shown
      an extremely variable frequency of Y mosaicism of 0-61%. We used Southern blot
      analysis and polymerase chain reaction (PCR) to detect the presence of Ycen, ZFY,
      SRY, and Yqh in 50 Mexican patients with UTS and different karyotypes to
      determine the origin of marker chromosomes and the presence of Y sequences. Our
      results indicated the origin of the marker chromosome in 1 patient and detected
      the presence of Y sequences in 4 45,X patients. Taken together, we found a 12%
      incidence of Y sequences in individuals with UTS. The amount of Y-derived
      material was variable, making the correlation between phenotype and molecular
      data difficult. Only 1 patient had a gonadoblastoma. We discuss the presence of Y
      chromosomes or Y sequences in patients with UTS and compare our frequency with
      that previously reported.

PMID- 9511974
TI  - Skeletal dysplasias with gracile bones: three new cases, including two offspring
      of a mother with a dwarfing condition.
AB  - We describe 3 new cases of a rare form of dwarfism (so-called "lethal skeletal
      dysplasia with gracile bones" or "osteocraniostenosis"), a condition
      characterized by thin, brittle bones and death in late gestation or early
      neonatal life. The first was a 37-week gestation female who died at delivery. She
      had facial anomalies and positional abnormalities of the hands and feet. The
      others were male stillborn sibs, who died in utero in the third trimester. Their
      mother had an undiagnosed dwarfing condition associated with body asymmetry,
      microcephaly, and unusual facial appearance. Both fetuses were documented by
      ultrasound to have short limbs and probable long bone fractures late in the
      second trimester. At autopsy, one fetus had no spleen and the other a hypoplastic
      spleen. Radiographically, all three cases had very thin diaphyses, diaphyseal
      fractures, and thin ribs and clavicles. In contrast to the first case who had a
      normally mineralized calvaria, the sibs had grossly deficient calvarial
      mineralization. Microscopically, endochondral ossification was qualitatively
      normal but quantitatively deficient in all three cases. The long bones,
      especially those of the sibs, lacked the well-defined outer cortex in the mid
      shaft normally seen by the third trimester. This failure of organization into the
      cortex and medulla suggests a failure of bone remodelling. Given the variable
      presentation in these cases, "lethal skeletal dysplasia with gracile bones" is
      probably a heterogeneous disorder. The recurrence in one family suggests that the
      mother has somatic/germline mosaicism of a lethal gene, expressed clinically as
      growth failure and asymmetry.

PMID- 9511975
TI  - Blepharo-Cheilo-Dontic (BCD) syndrome: report on four new patients.
AB  - We report on four Brazilian patients with, among other signs, cleft lip and
      palate, dental anomalies, ectropion of the lower eyelids, euryblepharon, and
      lagophthalmia. Two were sporadic cases and two were familial cases, a mother and
      her equally affected son. Recently, the reports with different combination of
      these signs were reviewed by Gorlin et al. [1996; Am J Med Genet 65:109-112] and
      named blepharocheilo-dontic (BCD) syndrome. Variable expressivity and autosomal
      dominant inheritance were observed.

PMID- 9511976
TI  - Prenatal diagnosis of autosomal recessive polycystic kidney disease (ARPKD):
      molecular genetics, clinical experience, and fetal morphology.
AB  - Autosomal recessive polycystic kidney disease (ARPKD) is one of the most common
      hereditary renal cystic diseases and has a high infant mortality. Prenatal
      diagnosis using fetal sonography can be unreliable, especially in early
      pregnancy. The ARPKD locus has been mapped to proximal chromosome 6p allowing
      haplotype-based prenatal diagnosis in "at-risk" families. From December 1994 to
      March 1997, we received 258 inquiries regarding prenatal evaluation and we have
      completed analyses in 212 families. To date, 65 prenatal analyses have been
      performed in 57 families. In the majority of the requesting families (45/57), the
      index children are deceased and their DNA was extracted from paraffin-embedded
      tissue. Eighteen fetuses were homozygous for the disease-associated haplotypes.
      In 12 of these fetuses, pathoanatomical examination demonstrated typical ARPKD
      changes consisting of dilated collecting ducts and the characteristic hepatic
      ductal plate malformation. These changes were detected in two fetuses as early as
      13 weeks gestational age. These cases represent the earliest demonstration of
      ARPKD-associated histopathology reported to date. One high risk fetus was carried
      to term and turned out to be unaffected. However, the diagnosis of ARPKD remained
      doubtful in the index patient. Forty-three fetuses were either heterozygous or
      homozygous for a nondisease-associated haplotype and all infants born were
      phenotypically unaffected at birth. In four cases, a recombination event occurred
      between the flanking markers and no genotypic prediction was possible. Three of
      these pregnancies were terminated and necropsy of the fetuses confirmed ARPKD,
      while one fetus was carried to term and showed no abnormalities at birth. These
      results show that haplotype-based prenatal testing is feasible and reliable in
      pregnancies "at risk" for ARPKD. An absolute prerequisite for these studies is an
      accurate diagnosis of ARPKD in previously affected sib(s).

PMID- 9511977
TI  - Alice Vance ("Das Barenweib"): a historical case of Nievergelt syndrome.
AB  - Several malformed individuals were presented at the World Exhibition in Antwerp
      in 1894. Among them was Mrs. Alice Vance from Mount Pleasant, Texas, with
      congenital limb defects, and Mr. Eugen Berry, who had asymmetrical, monstrous
      enlargement and macrodactyly of the feet, i.e., Proteus syndrome. After the World
      Exhibition Mrs. Vance presented herself to the public in Castan's Panopticon
      imitating a bear. She became famous under the stage name "Das Barenweib" ("the
      bear-like woman") and was examined by several German clinicians, and her
      malformations were considered to be of high scientific interest. Mrs. Vance had
      mesomelic dwarfism and her mother was known to have similar malformations. Her
      limb deficiencies were generally considered a unique congenital condition those
      days, and the diagnosis of "a maternally inherited malformation of the forearms
      and the shanks" [Daffner 1898: Munch Med Wochenschr 25:782] was made. Virchow
      [1897: Verh Berl Ges Ethnol Urgeschichte 29:624], feeling attacked by a daily
      newspaper stating that the physicians as well as the police of Berlin had missed
      the diagnosis of an "English disease," eventually exercised his authority and
      diagnosed Alice Vance as a "phocomelic." Clearly, she was not a phocomelic
      according to past and current definition of this term. Thus, from a historical
      point of view, the story illustrates how pressure from the daily press altered
      the definition of an up-to-then precisely defined medical term for decades.
      According to the clinical data and an X-ray report available from the literature,
      Alice Vance had a dominantly inherited type of mesomelic dwarfism. We propose the
      diagnosis of Nievergelt syndrome.

PMID- 9511978
TI  - Full mosaic monosomy 22 in a child with DiGeorge syndrome facial appearance.
AB  - We describe an abnormal premature male infant with mosaic monosomy of chromosome
      22. He had a unique facial appearance, similar to those with DiGeorge syndrome,
      and hypertonicity, limitation of extension at major joints, and flexion
      contractures of all fingers. This rare chromosomal aberration has been reported
      previously in 6 cases, three of them being nonmosaic and three mosaic patients.
      There was a great variability of expression among the anomalies of these
      patients. However, the most common anomalies were in the face and joints. A
      correlation between the severity of expression and percent of monosomic cells was
      not clear.

PMID- 9511979
TI  - Early treatment of Menkes disease with parenteral copper-histidine: long-term
      follow-up of four treated patients.
AB  - We report on the long-term clinical course of 4 boys with Menkes disease, treated
      from early infancy with parenteral copper-histidine, with follow-up over 10-20
      years. Three of the 4 had male relatives with a severe clinical course compatible
      with classical Menkes disease. As a consequence of early treatment, our patients
      have normal or near-normal intellectual development, but have developed many of
      the more severe somatic abnormalities of the related disorder, occipital horn
      syndrome, including severe orthostatic hypotension in 2. In addition, 1 boy
      developed a previously unreported anomaly, namely, massive splenomegaly and
      hypersplenism as a consequence of a splenic artery aneurysm. Previously reported
      molecular studies in 2 of these patients had shown gene defects which would have
      predicted a truncated and probably nonfunctional gene product. Despite the
      favorable effects on the neurological symptoms, parenteral copper treatment for
      Menkes disease should still be regarded as experimental. The development of more
      effective treatments must await a more precise delineation of the role which the
      Menkes protein plays in intracellular copper trafficking.

PMID- 9511980
TI  - MRI findings in macrocephaly-cutis marmorata telangiectatica congenita.
AB  - We describe a child with macrocephaly-cutis marmorata telangiectatica congenita
      (M-CMTC), cherry red macules, megalencephaly with hemifacial and segmental
      overgrowth, macrosomia, and cutis marmorata telangiectasia congenita of the
      trunk, and visceral and subcutaneous cavernous hemangiomas. The megalencephaly is
      accompanied by MRI findings of CNS dysgenesis with protrusion of the cerebellar
      tonsils through the foramen magnum (Chiari I), lumbar syrinx, and hydrops of the
      optic nerves. The report of this additional patient further confirms the newly
      described macrocephaly-cutis marmorata telangiectatica congenita as a distinct
      clinical phenotype.

PMID- 9511981
TI  - Bearing crosses: a historiography of genetics and embryology.
AB  - As we construct the fusion of medical embryology and medical genetics, it is
      important to be aware of how the history of genetics has been written to exclude
      embryology. This article looks at the rhetoric of genetics and how that rhetoric
      fits a paradigm of supersessionism. Supersessionism is often seen in the history
      of religion when one sect claims superiority to the original sect from whence it
      emerged. Such supersessionism portrays embryology as a failed research program,
      one that genetics now has saved. In some instances, biblical references have
      alluded to the failed nature of embryology. Although this article does not
      criticize the data of genetics, it takes issue with the historiography used by
      geneticists and seeks to show that the mergers between genetics and embryology
      are those between two equal partners and not between an inferior and superior
      member.

PMID- 9511982
TI  - Reevaluation of the importance of polymorphic HLA class II alleles and amino
      acids in the susceptibility of individuals of different populations to type I
      diabetes.
AB  - Several publications have shown that certain alleles at the HLA-DRB1, -DQA1, and 
      DQB1 loci are associated with insulin-dependent diabetes mellitus (IDDM). Many of
      these studies have claimed that HLA-DQalpha1Arg52 and DQbeta1Asp57 showed the
      strongest association with IDDM, but these results could not be confirmed in
      different populations. We have recently found that DRbeta1Lys71+ provided major
      susceptibility to IDDM and that DQbeta1Asp57- had an additive effect to
      DRbeta1Lys71+ [Zamani et al., 1994a: Eur J Hum Genet 2:177-184]. This was
      confirmed with haplotype analysis in multiplex IDDM families [Zamani et al.,
      1996a: J Med Genet 33:899-905]. Therefore, we have reanalyzed the data from the
      literature on the association of the human leucocyte antigen (HLA) DRB1, DQB1,
      and DQA1 with IDDM in different ethnic groups to determine whether different
      amino acids in the antigen binding cleft of HLA class II molecules play a
      preponderant role in the development of IDDM. The results showed that the
      DRbeta1Lys71+ allele provided the highest relative risk for IDDM in the Belgian,
      Danish, Greek Taiwanese, and Chinese population while this was not the case in
      Norwegians, Sardinians, and Algerians. Indeed, in the Sardinian and Algerian
      population the DRB1*0401 allele encoding Lys71+ is very rare. Nevertheless, the
      few positive cases were always in the patient group. We also measured the
      clinical relevance of the testing for DRbeta1Lys71, DQbeta1Asp57, and
      DQalpha1Arg52 by calculating a prevalence-corrected positive predictive value
      (PcPPV), a prevalence corrected negative predictive value (PcNPV), the
      sensitivity and specificity of these tests. The results indicated that the
      sensitivity of the test for DRbeta1Lys71+ was lower than for DQalpha1Ag52+ and
      DQbeta1Asp57-, while testing for DRbeta1Lys71+ was more specific than testing for
      DQbeta1Asp57- and DQalpha1Arg52+ and that the DRbeta1Lys71+ allele had a higher
      PcPPV than DQalpha1Arg52+ and DQbeta1Asp57- in all studied populations. These
      results also showed that testing for DRbeta1LyS71+/+ can be useful in IDDM risk
      assessment particularly in populations with a high prevalence (P) of IDDM such as
      the Danish (P[IDDM] = 0.65%). PcPPV for DRbeta1Lys71+/+ was 0.2313 in the Danish,
      indicating a 23.13% risk for an individual who is homozygous for the genotype
      DRbeta1Lys71+/+ to develop IDDM. Some mechanisms which might explain the role of
      these HLA class II alleles in susceptibility to IDDM are discussed.

PMID- 9511983
TI  - Host-cell-specific glycosylation of HIV-2 envelope glycoprotein.
AB  - Neutral complex-type N-glycans of the envelope glycoprotein 120 of HIV-2,
      propagated in different host cells, display cell-type specific variations. In
      order to identify typical structural elements, glycans were analysed by gel
      filtration, by enzymic sequencing and, in part, by matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry. The characteristic
      substituents of di- tri- and tetraantennary carbohydrate units thus observed
      include N-acetyllactosamine repeats, bisecting N-acetylglucosamine and fucose
      linked to the chitobiose core as well as to N-acetyllactosamine antennae. Each
      glycoprotein preparation displayed a characteristic set of glycoforms.

PMID- 9511984
TI  - Detection of four human milk groups with respect to Lewis blood group dependent
      oligosaccharides.
AB  - Neutral oligosaccharides in human milk samples from approximately 50 women were
      analysed applying a recently developed high-pH anion-exchange chromatographic
      method. Three different oligosaccharide patterns could be detected in accordance
      with milk groups that had been already described. These oligosaccharide groups
      correspond to the Lewis blood types Le(a-b+), Le(a+b-) and Le(a-b-). In addition
      to these oligosaccharide patterns, a new carbohydrate pattern was detected in a
      milk sample from a Le(a-b-) individual. Here, only nonfucosylated
      oligosaccharides and compounds bearing alpha1,3 linked fucosyl residues were
      found, whereas structures with alpha1,2 and alpha1,4 fucosyl linkages were
      missing. This finding led to the hypothesis that there are four different
      oligosaccharide milk groups that fit well to the genetic basis of the Lewis blood
      group system.

PMID- 9511985
TI  - Expression of A and H blood-group and of CD44 antigens during chemical rat
      colonic carcinogenesis.
AB  - Using an experimental model of rat colon adenocarcinoma, we have recently shown
      that the presence of H blood-group antigen on variants of the CD44 adhesion
      molecule carrying amino acids encoded by exon v6 (CD44v6), increased the cells'
      tumorigenicity. In the present study, colon adenocarcinomas were induced by 1,2
      dimethylhydrazine treatment in rats. Using immunohistochemistry, biopsies of
      normal, precancerous and carcinomatous colon mucosa were evaluated for expression
      A and H blood group antigens and CD44s and CD44v6 antigens. Normal rat colon
      showed strong and homogeneous expression of blood-group antigen A, but weak
      expression of H antigen. Several weeks before the appearance of tumours,
      dysplastic glands were strongly stained with anti-H reagents, while their A
      antigen was lost. Expression of CD44v6 was weak and restricted to some cells at
      the bottom of normal crypts. No obvious change was observed before appearance of
      severe dysplasia. In carcinomas, a strong but irregular expression of A, H and
      CD44v6 antigens was observed. In moderately differentiated carcinomas, A and H
      antigens were present at the apical surface of cells, whereas CD44v6 was found at
      the basolateral side. Only carcinomatous cells with loss of polarity, found in
      poorly differentiated cancers or infiltrated in the muscularis mucosae, were
      found to coexpress blood-group H or A and CD44v6 antigens at their surface.

PMID- 9511987
TI  - Cloning, sequencing and expression of the acylneuraminate lyase gene from
      Clostridium perfringens A99.
AB  - The acylneuraminate lyase gene from Clostridium perfringens A99 was cloned on a
      3.3 kb HindIII DNA fragment identified by screening the chromosomal DNA of this
      species by hybridization with an oligonucleotide probe that had been deduced from
      the N-terminal amino acid sequence of the purified protein, and another probe
      directed against a region that is conserved in the acylneuraminate lyase gene of
      Escherichia coli and in the putative gene of Clostridium tertium. After cloning,
      three of the recombinant clones expressed lyase activity above the background of
      the endogenous enzyme of the E. coli host. The sequenced part of the cloned
      fragment contains the complete acylneuraminate lyase gene (ORF2) of 864 bp that
      encodes 288 amino acids with a calculated molecular weight of 32.3 kDa. The lyase
      structural gene follows a noncoding region with an inverted repeat and a ribosome
      binding site. Upstream from this regulatory region another open reading frame
      (ORF1) was detected. The 3'-terminus of the lyase structural gene is followed by
      a further ORF (ORF3). A high homology was found between the amino acid sequences
      of the sialate lyases from Clostridium perfringens and Haemophilus influenzae
      (75% identical amino acids) or Trichomonas vaginalis (69% identical amino acids),
      respectively, whereas the similarity to the gene from E. coli is low (38%
      identical amino acids). Based on our new sequence data, the 'large' sialidase
      gene and the lyase gene of C. perfringens are not arranged next to each other on
      the chromosome of this species.

PMID- 9511986
TI  - Secretion of alpha1,3-galactosyltransferase by cultured cells and presence of
      enzyme in animal sera.
AB  - Glycosyltransferases are normally synthesized as membrane-anchored proteins.
      However, we recently found that the murine enzyme UDP-Gal:Gal beta1 -->4GLcNAc
      (Gal to Gal) alpha1,3 galactosyltransferase (alpha1,3GT) is secreted in a soluble
      form into media by mouse teratocarcinoma F9 cells (Cho SK, Yeh J-C, Cho M,
      Cummings RD (1996) J Biol Chem 271: 3238-46). To study the biosynthesis of this
      enzyme and whether secretion of the soluble enzyme is a general phenomenon, a
      solid-phase assay was developed for the alpha1,3GT activity. A recombinant and
      soluble form of the murine alpha1,3GT was produced in H293 cells (H293
      alpha1,3GT) to aid in optimizing the assay. Desialylated orosomucoid was used as
      an immobilized acceptor in coated microtiter plates. The formation of product was
      detected by a biotinylated human-derived anti-alpha-Gal IgG and streptavidin
      conjugated to either alkaline phosphatase or the recombinant bioluminescent
      protein aequorin. Enzyme activity was dependent on the concentrations of
      asialoorosomucoid, UDP-Gal, alpha1,3GT and the time of incubation. The assay was
      also useful in monitoring alpha1,3GT activity during enzyme enrichment
      procedures. Using this assay, we found that alpha1,3GT activity was present in
      both cell extracts and culture media of several mammalian cell lines. Enzyme
      activity was also present in the sera from several mammals, but activity was
      absent in the sera from either humans or baboons. Our results demonstrate the
      development of a novel assay for the alpha1,3GT and provide evidence that
      secretion of the enzyme is a common biological phenomenon.

PMID- 9511988
TI  - The heparin-binding lectin from ovine placenta: purification and identification
      as histone H4.
AB  - The heparin-binding lectin complex from ovine placental cotyledons was purified
      by affinity chromatography on heparin-agarose column. It showed three protein
      bands, which had molecular weights of 13000, 15000 and 17000 by sodium
      dodecylsulfate-polyacrylamide gel electrophoresis, and the presence of DNA by
      agarose gel electrophoresis. The protein components of the complex were separated
      by reverse-phase HPLC. The minimum inhibitory concentrations of
      glycosaminoglycans were significantly different for the lectin complex and the
      separated proteins, suggesting affinity changes upon DNA binding. The
      haemagglutinating activity specificity allowed the characterization of the
      fraction with a molecular weight of 13000 as the heparin-binding lectin. This
      protein was identified as histone H4 by internal sequencing, thus showing that
      this is the histone responsible for the heparin-binding property of the complex.
      The accompanying proteins were tentatively identified as histones H2A and H2B.

PMID- 9511989
TI  - Oligosaccharide-derivatized dendrimers: defined multivalent inhibitors of the
      adherence of the cholera toxin B subunit and the heat labile enterotoxin of E.
      coli to GM1.
AB  - Poly(propylene imine) dendrimers having four or eight primary amino groups and a
      Starburst (PAMAM) dendrimer having eight primary amino groups were used as core
      molecules, to which phenylisothiocyanate derivatized (PITC) galbeta1-3galNAcbeta1
      4[sialic acid alpha2-3]-galbeta1-4glc (oligo-GM1) residues were covalently
      attached to yield multivalent oligosaccharides. The synthesis of the oligo-GM1
      PITC derivatized dendrimers was monitored using high performance thin layer
      chromatography, infrared spectroscopy, sialic acid content, and mass
      spectroscopy. The ability of multivalent oligo-GM1-PITC dendrimers to inhibit the
      binding of 125I-labeled cholera toxin B subunit and the heat labile enterotoxin
      of E. coli to GM1-coated microtiter wells was determined. IC50s obtained for the
      oligo-GM1-PITC dendrimers, GM1, and the oligosaccharide moiety of GM1 indicated
      that the derivatized dendrimers inhibited binding of the choleragenoid and the
      heat labile enterotoxin to GM1-coated wells at a molar concentration five- to 15
      fold lower than native GM1 and more than 1,000-fold lower than that of the free
      oligosaccharide.

PMID- 9511991
TI  - Capillary zone electrophoresis for the study of the binding of antithrombin to
      low-affinity heparin.
AB  - When low-affinity interactions between glycosaminoglycans and precious proteins
      are studied, it is imperative to design an experimental set-up that consumes as
      little material as possible. To evaluate the applicability of the CZE technique
      to this problem, we explored the interaction between antithrombin and low
      affinity heparin. In a series of CZE experiments we demonstrated that the
      mobility of antithrombin increases gradually as increased concentrations of low
      affinity heparin were added to the electrolyte. The results were, as expected,
      consistent with the general algorithm for monovalent binding. The binding
      constant was estimated at 20+/-6 microM in excellent agreement with the value
      reported in the literature.

PMID- 9511990
TI  - Developmentally regulated O-acetylated sialoglycans in the central nervous system
      revealed by a new monoclonal antibody 493D4 recognizing a wide range of O
      acetylated glycoconjugates.
AB  - We have previously detected an alkali-labile and developmentally regulated
      antigen in rat embryonic cerebral cortex, which may be 9-O-acetylsialylated GT3
      ganglioside (Hirabayashi Y, Hirota M, Suzuki Y, Matsumoto M, Obata K, Ando S
      (1989) Neurosci Lett 106:193-98). In this study we established a mouse monoclonal
      antibody, 493D4, that recognizes 9-O-acetyl GT3 ganglioside, but not non-O-acetyl
      gangliosides. This antibody also reacted with 9-O-acetyl GD3 to a much lesser
      extent. By using this antibody, we found that O-acetyl GT3 as well as O-acetyl
      GD3 were expressed strongly in fetal murine cerebral cortex and decreased to an
      undetectable level after birth. With the assistance of TLC-immunostaining using
      493D4 together with Q-Sepharose column chromatography, O-acetyl gangliosides of
      bovine brain were purified and the structural analysis showed the presence of O
      acetyl GD3, O-acetyl LD1, O-acetyl GD2 and O-acetyl GD1b in the adult brain as
      extremely minor components. Interestingly, the antibody 493D4 could detect O
      acetyl sialoglycoproteins in rat brain tissues. One of the major immunoreactive
      proteins was shown to be synaptophysin, an integral membrane protein specifically
      present in synaptic vesicles. This monoclonal antibody was therefore useful for
      sensitive detection of both O-acetylated gangliosides and glycoproteins with O
      acetylated sialic acids.

PMID- 9511992
TI  - The importance of oligosaccharides to rheumatic disease: a personal perspective.

PMID- 9511993
TI  - Binding of ovarian cancer cells to immobilized hyaluronic acid.
AB  - Ovarian cancer has the highest mortality rate of any gynaecological malignancy.
      This is caused by metastatic deposits obstructing the intestinal tract. Very
      little is known about the molecules involved in the initial attachment of the
      metastatic tumour cells to the peritoneal mesothelial lining. Previously, we
      showed that many ovarian tumour lines express the adhesion molecule, CD44, on
      their cell surface. The major ligand for CD44 is the extracellular matrix
      glycosaminoglycan, hyaluronic acid (HA). Because mesothelial cells have a
      pericellular cost that contains large amounts of HA, it was postulated that the
      CD44/HA interaction is an important stage in ovarian cancer spread. However, it
      was difficult to demonstrate this interaction in an in vitro adhesion assay with
      mesothelial cells as most of the HA, and presumably the bound tumour cells, were
      lost from the mesothelial cells during the washing steps of the assay. In order
      to try and clarify the situation, the adhesion of six ovarian tumour lines to
      immobilized HA was measured. Four lines expressed high levels of CD44 and two
      lines expressed negligible amounts. Preliminary experiments were carried out with
      one of the CD44-expressing lines. After coating a plate overnight with 3 mg ml(
      1) HA, the 5 min adhesion of this line varied between 2% and 73% according to the
      type of plate that was used. Falcon Micro Test III flexible plates gave the
      highest adhesion and was used for further experiments. Plates were coated with
      concentrations of HA between 0.001 mg ml(-1) and 3 mg ml(-1). All CD44 expressing
      lines adhered to HA, but the maximum adhesion and the adhesion strength varied
      with the line studied and was not closely related to the total CD44 expression.
      These results suggest that CD44 on ovarian tumour cells binds to HA on
      mesothelial cells. As much of the HA can be very easily lost from the mesothelial
      cell surface, additional factors such as the strength of the CD44/HA interaction,
      and the formation of bonds by the tumour cells with other membrane adhesion
      molecules, such as integrins, are also important in promoting tumour spread.

PMID- 9511994
TI  - Role of decorin on in vitro fibrillogenesis of type I collagen.
AB  - Tendon and corneal decorins are differently iduronated dermatan
      sulphate/proteoglycan (DS/PG) and the biochemical parameter that differentiates
      type I collagens is the hydroxylysine glycoside content. We have examined the
      effect of tendon and corneal decorins on the individual phases (tlag, dA/dt) of
      differently glycosylated type I collagens fibril formation, at molar ratios
      PG:collagen monomer ranging from 0.15:1 to 0.45:1. The results obtained indicate
      that decorins exert a different effect on the individual phases of fibril
      formation, correlated to the degree of glycosylation of collagen: at the same
      PG:collagen ratio the fibril formation of highly glycosylated corneal collagen is
      more efficiently inhibited than that of the poorly glycosylated one (tendon).
      Moreover tendon and corneal decorins exert a higher control on the
      fibrillogenesis of homologous collagen with respect to the heterologous one.
      These data suggest a possible tissue-specificity of the interaction decorin/type
      I collagen correlated to the structure of the PG and collagen present in
      extracellular matrices.

PMID- 9511995
TI  - Sialyl-Lewis-X, Gleason grade and stage in non-metastatic human prostate cancer.
AB  - Early stage prostate cancers are now commonly encountered because of widespread
      use of screening tools. Increased cancer cell proliferation, and expression of
      sialyl Lewis could be important as predictors of clinical behaviour and survival
      in addition to histologic grade. In this study, the expression of sialyl-LewisX
      (sLeX) was determined by immunohistochemical methods in 38 routinely processed
      prostate biopsies and transurethral resections preceding radical prostatectomies
      for organ confined prostate cancers. Histologic grades were determined from
      pathologic reports and divided into two (2) groups; low grade (Gleason score 2-4)
      and medium grade (Gleason score 5-7). Tumour stages were based on radical
      prostatectomy reports and 29 were T2 and 9 were T3. SLeX was positive in 10 of 14
      (71.4%) low grade and 14 of 24 (62.5%) medium grade cancers; 22/29 (75.9%) T2 and
      8/9 (88.9%) T3 were sLeX positive; 1 of 15 (7.2%) low grade and 5 of 24 (20.8%)
      medium grade were strongly positive (3+) or overexpressing sLeX. Overexpression
      of sLeX was a feature of medium grade cancer, suggesting that localized prostate
      cancers with increased potential for progression and metastasis exist in the
      clinically non-metastatic group.

PMID- 9511996
TI  - Glycosidases in mucin-dwelling protozoans.
AB  - A range of protozoans were tested for the presence of glycosidases using p
      nitrophenyl sugars as substrates. Some of the organisms were mucin dwellers
      whereas others were blood borne parasites. It had been hypothesized that
      glycosidase production would be significantly higher in the mucin dwellers. The
      results obtained demonstrated that the urogenital protozoans Tritrichomonas
      foetus and Trichomonas vaginalis produced a vast range of glycosidases which
      included those required for mucin breakdown. The gut dwelling protozoans Giardia
      lamblia and Entamoeba histolytica both produced beta-N-acetylglucosaminidase.
      G.lamblia also had detectable beta N-acetylgalactosaminidase activity, and small
      amounts of beta mannosidase were found in the extracts from E. histolytica. In
      contrast, little or no glycosidase activity was detected under the same
      experimental conditions in Leishmania donovani, Trypanosoma brucei or T. cruzi.
      The mucin dwelling protozoans all produce beta-N-acetylglucosaminidase but only
      the Trichomonads produced the range of enzymes required for complete breakdown of
      mucin. This seems to suggest that mucin breakdown is not a characteristic of all
      mucin dwelling protozoans.

PMID- 9511997
TI  - Purification and partial characterization of beta-galactosidase from
      Tritrichomonas foetus.
AB  - The work presented in this paper describes the purification and properties of a
      beta-galactosidase from the protozoan Tritrichomonas foetus. An inexpensive and
      straightforward method for extraction of the enzyme involving ammonium sulphate
      precipitation, ion exchange and affinity chromatography resulted in a high level
      of purification. After purification beta-N-acetylglucosaminidase was the only
      enzyme present as a contaminant at a significant level. The beta-galactosidase
      isolated had a pH optimum of 5.8. The Km determined at pH 5.8 was found to be 2.2
      mM. Interesting results were obtained when studies were carried out to determine
      the effect of various metal ions on enzyme activity. Of the metal ions used in
      this study only manganese ions were found to activate the enzyme. This seems to
      be a characteristic of trichomonad enzymes, as N-acetyl-beta-glucosaminidase,
      alpha-galactosidase and N-acetyl-alpha-galactosaminidase are also activated by
      manganese ions. The strongest inhibition was recorded with lead and to a lesser
      extent by zinc. The result with lead is not unexpected as the heavy metal is
      known to cause irreversible inhibition by binding to the amino-acid backbone of
      the enzyme. The result with zinc is interesting as high levels of zinc are
      present and trichomonads are known to be apathogenic in semen. The purified beta
      galactosidase was found to have the capacity to hydrolyse lactose (Gal beta1-4
      Glc), lacto-N-biose 1 (Gal beta1-3 GlcNAc) and N-acetyllactosamine (Gal beta1-4
      GlcNAc). When the enzyme was applied to a non-denaturing polyacrylamide gel a
      single band was observed when stained with Coomassie brilliant blue. This band
      coincided with that obtained when the gel was stained with p-nitrophenyl beta
      galactopyranoside. When the same gel was incubated with p-nitrophenyl N-acetyl
      beta-glucopyranoside a band was detected which did not coincide with that of beta
      galactosidase. Since the beta-N-acetylglucosaminidase enzyme does not move to the
      same position on a non-denaturing gel as the beta-galactosidase, we will use this
      technique to isolate the latter enzyme and determine the N-terminal sequence as a
      prelude to cloning and further study of the gene.

PMID- 9511998
TI  - Carrier-mediated high affinity uptake system for histamine in astroglial and
      cerebral endothelial cells.

PMID- 9511999
TI  - Neuroprotection, neuroregeneration, and interaction with insulin-like growth
      factor-I: novel non-anticoagulant action of glycosaminoglycans.
AB  - We present recent developments in the area of glycosaminoglycans (GAGs) and their
      possible interaction with insulin-like growth factor-I (IGF-I). GAGs are
      constituents of proteoglycans, and the combination of a core protein and a
      specific GAG makes a unique proteoglycan with a precise developmental pattern and
      with the ability to bind growth factors. This process is apparently regulated by
      the moiety of the peripheral GAGs. The supplementation of GAGs promotes
      neuritogenesis in vitro and stimulates nerve regrowth and muscle reinnervation,
      an effect correlated with an increase in trophic factor mRNA expression. In the
      case of neonatal nerve lesion, there is in addition an enhanced motor neuron
      survival, accompanied by higher levels of IGF-I in plasma and denervated muscle.
      The neurotrophic and neuroregenerative effects of exogenous GAGs were also
      observed in motor neuron disease in the wobbler mouse.

PMID- 9512000
TI  - Member of the peroxisome proliferator-activated receptor family of transcription
      factors is differentially expressed by oligodendrocytes.
AB  - Peroxisome proliferator-activated receptors (PPARs) are ligand-activated
      transcription factors that form a subfamily within the steroid hormone receptor
      group. Recent work has shown that one member of this group, PPARgamma, plays a
      central role in adipocyte differentiation. As oligodendrocytes are major lipid
      producing cells, we investigated whether members of the PPAR family were present
      in oligodendrocytes and whether known PPAR activators affect oligodendrocyte
      differentiation. Polymerase chain reaction and nuclease protection analyses
      demonstrated that the principal PPAR present in optic nerve and sciatic nerve is
      PPARdelta, whereas adipose tissue expresses mainly PPARgamma. In situ
      hybridization of primary glial cultures revealed PPARdelta message in
      oligodendrocytes but not in astrocytes. PPARdelta message was strongly expressed
      in immature oligodendrocytes, suggesting a role in oligodendrocyte
      differentiation. Glial cultures containing immature oligodendrocytes were treated
      with CP 68,722 and bromopalmitate, compounds known to activate PPARs in
      adipocytes. These agents increased the number of oligodendrocytes with membrane
      sheets three- to fourfold, accelerated the rate of formation of membrane sheets,
      and increased the size of the membrane sheets. The abundant expression of
      PPARdelta in oligodendrocytes in vivo and in vitro suggests that this PPAR plays
      a critical role in oligodendrocyte development and that PPAR activators can be
      used to manipulate oligodendrocyte maturation in tissue culture.

PMID- 9512001
TI  - Prolongation by bifemelane of potentiation of AP1 DNA binding in hippocampal CA1
      subfield of gerbils with transient forebrain ischemia.
AB  - In eukaryotes, protein de novo synthesis is mainly under the control of
      transcription factors at the level of gene transcription in cell nuclei. Gel
      retardation electrophoresis was employed for determination of DNA-binding
      activity of the transcription factor activator protein-1 (AP1), which is a dimer
      between c-Fos and c-Jun protein families. Binding of a radiolabeled double
      stranded oligonucleotide probe for AP1 was rapidly potentiated in the CA1 and CA3
      subfields and the dentate gyrus of the hippocampus of gerbils with forebrain
      ischemia for 5 min. Similarly marked potentiation was seen in the thalamus and
      the striatum, but not in the frontal cortex, following the recirculation of blood
      supply. The potentiation was transient in the vulnerable CA1 subfield, but was
      rather persistent in the thalamus and the striatum in addition to the resistant
      CA3 subfield and dentate gyrus. However, administration of the neuroprotective
      drug bifemelane (10 to 20 mg/kg, i.p.) resulted in prolongation of the
      potentiation of AP1 binding in the CA1 subfield up to 6 hr after ischemia,
      without significantly affecting that in other central structures. Limited
      proteolysis revealed that bifemelane induced expression of the AP1 consisting of
      constructive proteins different from those expressed in control animals in the
      CA1 subfield. These results suggest that bifemelane may protect neuronal cells
      against ischemic injuries through molecular mechanisms associated with
      prolongation of the potentiation of AP1 binding in the vulnerable CA1 subfield
      after ischemia.

PMID- 9512002
TI  - Non-NMDA excitatory amino acid receptors in the ventral tegmental area mediate
      systemic dizocilpine (MK-801) induced hyperlocomotion and dopamine release in the
      nucleus accumbens.
AB  - This study investigated the putative role of non-NMDA excitatory amino acid (EAA)
      receptors in the ventral tegmental area (VTA) for the increase in dopamine (DA)
      release in the nucleus accumbens (NAC) and behavioral stimulation induced by
      systemically administered dizocilpine (MK-801). Microdialysis was utilized in
      freely moving rats implanted with probes in the VTA and NAC. Dialysates from the
      NAC were analyzed with high-performance liquid chromatography for DA and its
      metabolites. The VTA was perfused with the AMPA and kainate receptor antagonist
      CNQX (0.3 or 1 mM) or vehicle. Forty min after onset of CNQX or vehicle perfusion
      of the VTA, MK-801 (0.1 mg/kg) was injected subcutaneously. Subsequently, typical
      MK-801 induced behaviors were also assessed in the same animals by direct
      observation. MK-801 induced hyperlocomotion was associated with a 50% increase of
      DA levels in NAC dialysates. Both the MK-801 evoked hyperlocomotion and DA
      release in the NAC was antagonized by CNQX perfusion of the VTA in a
      concentration-dependent manner. None of the other rated MK-801 evoked behaviors,
      e.g. head weaving or sniffing, were affected by CNQX perfusion of the VTA. By
      itself the CNQX or vehicle perfusion of the VTA alone did not affect DA levels in
      NAC or any of the rated behaviors. These results indicate that MK-801 induced
      hyperlocomotion and DA release in the NAC are largely elicited within the VTA via
      activation of non-NMDA EAA receptors, tentatively caused by increased EAA
      release. Thus, the locomotor stimulation induced by psychotomimetic NMDA receptor
      antagonists may not only reflect impaired NMDA receptor function, but also
      enhanced AMPA and/or kainate receptor activation in brain, e.g., in the VTA. In
      view of their capacity to largely antagonize the behavioral stimulation induced
      by psychotomimetic drugs, such as MK-801, AMPA, and/or kainate receptor
      antagonists may possess antipsychotic efficacy.

PMID- 9512003
TI  - Mineralocorticoid receptor-mediated enhancement of neuronal excitability and
      synaptic plasticity in the dentate gyrus in vivo is dependent on the beta
      adrenergic activity.
AB  - The dentate gyrus neurons in the hippocampus contain a high density of both
      mineralocorticoid and adrenergic receptors. By in vivo extracellular recording
      from adrenalectomized rats we investigated the possible relationships between the
      two systems with regard to neuronal excitability and activity-dependent synaptic
      plasticity. Pretreatment with aldosterone significantly enhanced both basal
      neuronal excitability and tetanically evoked synaptic plasticity in
      adrenalectomized, but not sham-operated rats. The enhancement was blocked by
      spironolactone, indicating a mineralocorticoid receptor-dependent effect. The
      adrenomedullary hormone epinephrine also significantly enhanced synaptic
      plasticity via activation of beta-adrenergic receptors. Beta-adrenergic
      antagonist propranolol, infused directly into the dentate gyrus granule cell
      layer, significantly reduced the effect of aldosterone on neuronal excitability
      and partly canceled the aldosterone-enhanced synaptic plasticity. No effect of
      propranolol was found after its amygdaloid infusion. The mineralocorticoid
      receptor antagonist spironolactone did not affect the epinephrine-induced
      effects. These results indicate that the pretreated adrenal steroids interact
      with the catecholaminergic system in the dentate gyrus of adrenalectomized rats
      and that the functional beta-adrenergic pathway is involved in the mechanism of
      mineralocorticoid-induced cellular effects in vivo.

PMID- 9512004
TI  - Prenatal hippocampal granule cells in primary cell culture form mossy fiber
      boutons at pyramidal cell dendrites.
AB  - Mossy fiber boutons are the sites of synaptic signalling between hippocampal
      granule and pyramidal neurons. We studied the formation and localization of these
      terminals during development of prenatal hippocampal neurons in primary culture.
      Using the synaptic vesicle membrane proteins synaptophysin and synaptoporin as
      markers we observed that both proteins were mainly localized in perikarya and
      processes of fetal hippocampal neurons during the first days in vitro (DIV).
      Following DIV 6 synaptophysin was present in small terminals. After DIV 20 in
      addition large terminals immunoreactive for synaptophysin and synaptoporin were
      found, which were identified by electron microscopy as mossy fiber boutons
      impinging on pyramidal neuron dendrites. Synaptic vesicles and endosomes in the
      mossy fiber boutons were labeled when incubated with exogenous horseradish
      peroxidase, indicating that they were competent for exo-endocytosis. Taken
      together, our data show that hippocampal granule neurons grown in dissociated
      primary cultures form mossy fiber boutons containing synaptophysin and
      synaptoporin at pyramidal cell dendrites. Since the composition and the
      characteristic morphology of mossy fiber boutons formed in vitro is the same as
      observed in vivo we conclude that their development follows an intrinsic program.

PMID- 9512005
TI  - Transient compartmental expression of neurocan in the developing striatum of the
      rat.
AB  - The expression of the chondroitin sulfate proteoglycan neurocan was examined in
      the developing striatum of the rat and compared with the distribution of
      dopaminergic terminals. Neurocan immunoreactivity shows a homogeneous pattern in
      the embryonic striatum. In the postnatal striatum, neurocan was first expressed
      within the matrix but not the patch compartments, and subsequently within both.
      These results suggest that chondroitin sulfate proteoglycans are involved in
      formation of connections between the substantia nigra and striatum.

PMID- 9512006
TI  - Glucocorticoid induction of the alpha2,6 sialyltransferase enzyme in a mouse
      neural cell line.
AB  - Combined sialyltransferase (ST) activities were induced in the HN9 hippocampal
      cell line following treatment with the synthetic glucocorticoid dexamethasone
      (dex) for 24 hr. Induction occurred in a dose-dependent manner, with the maximum
      induction of a 2-fold increase over control enzyme levels occurring at a
      concentration of 10(-8) M dex. A minimum of 6 hr pretreatment with drug was
      required before significant induction could be detected and elevated enzyme
      levels persisted for up to 48 hr post-treatment. The induced form of the enzyme
      showed an increase in reaction maximum velocity (Vmax) while showing no change in
      affinity (Km) for the acceptor substrate asialofetuin. The alpha2,6 ST enzyme was
      demonstrated to be the primary enzyme induced and there was no change in
      expression of the alpha2,3 ST enzyme. Lectin blot analysis demonstrated an
      increase in the levels of the alpha2,6-linked cellular sialoglycoproteins and a
      parallel decrease in the alpha2,3 sialoglycoprotein levels.

PMID- 9512007
TI  - Alteration of nitric oxide synthase activity upon oxidative stress in cultured
      retinal cells.
AB  - In the present study we examined the effect of oxidative stress-mediated
      hydroperoxide formation on the activity of nitric oxide synthase (NOS) in retinal
      cells in culture. Oxidative stress was induced in the presence of Fe2+ and
      ascorbate or Fe2+ alone and compared to H2O2-induced maximal cellular oxidation,
      and was measured by following the formation of intracellular hydroperoxides with
      the probe DCFH2 (2',7'-dichlorodihydrofluorescein). After a 15-min exposure to
      the oxidants, formation of hydroperoxides was significantly increased in the
      presence of 100 microM Fe2+ (about twofold), as compared to the control.
      Coadministration of Fe2+ and ascorbate (Fe-Asc) did not affect DCF fluorescence,
      but highly reduced the intracellular pH (pHi = 6.32 +/- 0.08), in comparison with
      control conditions (pHi = 7.05 +/- 0.11), as determined with the probe BCECF
      (2',7'-bis-(carboxyethyl)-5(and-6) carboxyfluorescein). Nevertheless,
      preincubation of Fe-Asc at acidic pH also increased the formation of
      hydroperoxides. Oxidative stress induced in the presence of Fe-Asc (at pH 6.5)
      significantly decreased the activity of NOS by 20% of control activity, as
      determined by the formation of [14C]citrulline. Fe-Asc (pH 6.5) also reduced the
      production of cyclic GMP (cGMP) in retinal cells by 1.5-fold, although a
      decrement in pH from 7.4 to 6.5 was not sufficient to decrease cGMP production.
      These data suggest that NO. production may be compromised in the presence of Fe
      Asc. Moreover, neither 4 mM dithiotreitol (DTT) nor 4 mM glutathione (GSH)
      altered the production of cGMP in retinal cells submitted to oxidative stress. A
      reduction in NO. generation upon oxidative stress may reduce major damaging
      effects induced by ONOO- in cultured retinal cells.

PMID- 9512008
TI  - [U-13C]glutamate metabolism in astrocytes during hypoglycemia and hypoxia.
AB  - The ability of cultured astrocytes to metabolize [U-13C]glutamate in the absence
      of glucose was investigated by utilizing 13C nuclear magnetic resonance
      spectroscopy to identify 13C-labeled metabolites. Control cultures (3 mM
      glucose), hypoglycemic cultures (glucose-deprived), severe hypoglycemic cultures
      (glucose-deprived, 0.5 mM iodoacetate as an inhibitor of glycolysis),
      hypoglycemic/hypoxic cultures, and cultures deprived of all additional substrates
      were incubated for 2 hr in medium containing 0.5 mM glutamate (50% [U
      13C]glutamate). Glucose deprivation alone had little effect on removal of
      glutamate from the culture medium, but the presence of iodoacetate or incubating
      cultures in a low-oxygen atmosphere decreased glutamate clearance. Only the
      withdrawal of all substrates other than glutamate decreased glutamine synthesis.
      Metabolism of glutamate through the tricarboxylic acid (TCA) cycle was evident by
      the appearance of [1,2,3-13C]glutamate and [U-13C]aspartate in cell extracts and
      [U-13C]lactate in cell media. Lactate derived from TCA cycle intermediates was
      significantly reduced after glucose deprivation and even more so after severe
      hypoglycemia. Release of glutamate from astrocytes was observed under all
      incubation conditions. [U-13C]Aspartate was not detected in control media but was
      released from glucose-deprived cells when oxygen was available. Increased release
      was observed in the presence of iodoacetate. After withdrawal of all substrates
      other than glutamate, [U-13C]aspartate was the only metabolite observed
      intracellularly, whereas aspartate, glutamine, and 5-oxoproline were detected in
      the incubation medium. The present results indicate that glutamate-to-aspartate
      conversion is preferentially utilized by astrocytes when oxygen is available but
      glycolysis is impaired.

PMID- 9512009
TI  - Altered expression of microtubule-associated protein 1B in cerebral cortical
      structures of pentylenetetrazole-treated rats.
AB  - Using Northern blot, immunoblotting, immunocytochemistry, and in situ
      hybridization, we show that a single administration of the convulsant
      pentylenetetrazole leads to robust, long-term changes in microtubule-associated
      protein 1B and its mRNA, in the adult rat brain. The first increases in MAP1B
      mRNA were detected at 15 hr following pentylenetetrazole administration in the
      temporal (Te2) and perirhinal cortex followed by increases in microtubule
      associated protein 1B immunoreactivity at 72 hr postseizure. In contrast, the
      levels of microtubule-associated protein 1B mRNA and protein in layers I-II of
      the retrosplenial and parietal cortex (Par2) declined visibly by 24 hr and 72 h,
      respectively, post-seizure. The changes included loss of staining in layers I-II
      and development of structures resembling "strings-of-beads" along the fibers of
      projection neurons of layer V. The levels of microtubule-associated protein 1B
      mRNA in the entorhinal cortex peaked at later times (72 h), especially in layers
      II-III, and returned to control levels by 10 days. Whereas the levels of
      microtubule-associated protein 1B immunoreactivity in the retrosplenial and
      parietal cortex recovered by 5-10 days, it persisted at high levels through day
      35 in layer V of the temporal cortex (Te2), layers II-III of the perirhinal
      cortex and layers I-II of the lateral entorhinal cortex. These results indicate
      that seizure activity leads to long-term upregulation of genes coding for
      structural elements that are characteristic of the immature brain such as
      microtubule-associated protein 1B.

PMID- 9512010
TI  - Apolipoprotein E (ApoE) peptide regulates tau phosphorylation via two different
      signaling pathways.
AB  - Previous studies have shown that treating rat cortical neurons in primary culture
      with apolipoprotein E (apoE) peptide increased cytoplasmic Ca2+ by 2 mechanisms:
      1) an influx of extracellular Ca2+ resulting from the activation of a cell
      surface Ca2+ channel; and 2) release of Ca2+ from internal Ca2+ stores via a G
      protein-coupled pathway (Wang and Gruenstein, 1997). These studies employed a
      biologically active apoE synthetic peptide (apoEdp) derived from the receptor
      binding domain of apoE. In the present study we examined whether activation of
      these 2 signal transduction pathways affects phosphorylation of microtubule
      associated protein tau. The levels of tau phosphorylation at thr231, ser235, and
      ser396 were quantified by ELISA employing monoclonal antibodies PHF-6, SMI33, and
      PHF-1. ApoEdp treatment resulted in a concentration- and time-dependent
      dephosphorylation of tau at all 3 phosphorylation sites. The apoEdp-induced
      dephosphorylation of tau at thr231, and ser235 was dependent on the influx of
      extracellular Ca2+, while dephosphorylation at ser396 was mediated by a pertusis
      toxin-sensitive G-protein pathway. The involvement of protein phosphatases in
      mediating the apoEdp-induced dephosphorylation of tau was examined. Pretreatment
      with the protein phosphatase 2B inhibitor cyclosporin A blocked the apoEdp
      induced dephosphorylation of tau at thr231 and ser235 but not at ser396.
      Pretreatment with the protein phosophatase 2A/1 inhibitor okadaic acid blocked
      the apoEdp-induced dephosphorylation of tau at all 3 sites, while pretreatment
      with the protein phosphates 1 inhibitor tautomycin was without effect. The
      present study suggests that apoE may affect several Ca2+-associated signal
      transduction pathways that increase the activity of protein phosphatases 2A and
      2B, which in turn dephosphorylate tau.

PMID- 9512011
TI  - Static and dynamic roles of extracellular loops in G-protein-coupled receptors: a
      mechanism for sequential binding of thyrotropin-releasing hormone to its
      receptor.
AB  - Small ligands generally bind within the seven transmembrane-spanning helices of G
      protein-coupled receptors, but their access to the binding pocket through the
      closely packed loops has not been elucidated. In this work, a model of the
      extracellular loops of the thyrotropin-releasing hormone (TRH) receptor (TRHR)
      was constructed, and molecular dynamics simulations and quasi-harmonic analysis
      have been performed to study the static and dynamic roles of the extracellular
      domain. The static analysis based on curvature and electrostatic potential on the
      surface of TRHR suggests the formation of an initial recognition site between TRH
      and the surface of its receptor. These results are supported by experimental
      evidence. A quasi-harmonic analysis of the vibrations of the extracellular loops
      suggest that the low-frequency motions of the loops will aid the ligand to access
      its transmembrane binding pocket. We suggest that all small ligands may bind
      sequentially to the transmembrane pocket by first interacting with the surface
      binding site and then may be guided into the transmembrane binding pocket by
      fluctuations in the extracellular loops.

PMID- 9512012
TI  - Differential partitioning of pulmonary surfactant protein SP-A into regions of
      monolayers of dipalmitoylphosphatidylcholine and
      dipalmitoylphosphatidylcholine/dipalmitoylphosphatidylglycerol.
AB  - The interaction of the pulmonary surfactant protein SP-A fluorescently labeled
      with Texas Red (TR-SP-A) with monolayers of dipalmitoylphosphatidylcholine (DPPC)
      and DPPC/dipalmitoylphosphatidylglycerol 7:3 w/w has been investigated. The
      monolayers were spread on aqueous subphases containing TR-SP-A. TR-SP-A
      interacted with the monolayers of DPPC to accumulate at the boundary regions
      between liquid condensed (LC) and liquid expanded (LE) phases. Some TR-SP-A
      appeared in the LE phase but not in the LC phase. At intermediate surface
      pressures (10-20 mN/m), the protein caused the occurrence of more, smaller
      condensed domains, and it appeared to be excluded from the monolayers at surface
      pressure in the range of 30-40 mN/m. TR-SP-A interaction with
      DPPC/dipalmitoylphosphatidylglycerol monolayers was different. The protein did
      not appear in either LE or LC but only in large aggregates at the LC-LE boundary
      regions, a distribution visually similar to that of fluorescently labeled
      concanavalin A adsorbed onto monolayers of DPPC. The observations are consistent
      with a selectivity of interaction of SP-A with DPPC and for its accumulation in
      boundaries between LC and LE phase.

PMID- 9512013
TI  - Behavior of N-phenylmaleimide-reacted muscle fibers in magnesium-free rigor
      solution.
AB  - Using x-ray diffraction and mechanical stiffness, the response of N
      phenylmaleimide (NPM)-reacted cross-bridges to solutions containing different
      amounts of ATP and Mg2+ has been studied. In relaxing solution containing greater
      than millimolar amounts of ATP and Mg2+, NPM-treated muscle fibers give x-ray
      diffraction patterns and stiffness records, which are nearly indistinguishable
      from those of untreated relaxed fibers. In a solution devoid of added ATP, but
      with Mg2+ (rigor(+Mg) solution), the muscle fibers still give x-ray diffraction
      patterns and mechanical responses characteristic of relaxed muscle. The new
      finding reported here is that in a solution devoid of both ATP and Mg2+ (rigor(
      Mg) solution containing EDTA with no added ATP), NPM-reacted cross-bridges do
      give rigor-like behavior. This is the first report that NPM-reacted cross
      bridges, at least in the presence of EDTA, are capable of going into a strongly
      binding conformation.

PMID- 9512014
TI  - Loss of conformational stability in calmodulin upon methionine oxidation.
AB  - We have used electrospray ionization mass spectrometry (ESI-MS), circular
      dichroism (CD), and fluorescence spectroscopy to investigate the secondary and
      tertiary structural consequences that result from oxidative modification of
      methionine residues in wheat germ calmodulin (CaM), and prevent activation of the
      plasma membrane Ca-ATPase. Using ESI-MS, we have measured rates of modification
      and molecular mass distributions of oxidatively modified CaM species (CaMox)
      resulting from exposure to H2O2. From these rates, we find that oxidative
      modification of methionine to the corresponding methionine sulfoxide does not
      predispose CaM to further oxidative modification. These results indicate that
      methionine oxidation results in no large-scale alterations in the tertiary
      structure of CaMox, because the rates of oxidative modification of individual
      methionines are directly related to their solvent exposure. Likewise, CD
      measurements indicate that methionine oxidation results in little change in the
      apparent alpha-helical content at 28 degrees C, and only a small (0.3 +/- 0.1
      kcal mol(-1)) decrease in thermal stability, suggesting the disruption of a
      limited number of specific noncovalent interactions. Fluorescence lifetime,
      anisotropy, and quenching measurements of N-(1-pyrenyl)-maleimide (PMal)
      covalently bound to Cys26 indicate local structural changes around PMal in the
      amino-terminal domain in response to oxidative modification of methionine
      residues in the carboxyl-terminal domain. Because the opposing globular domains
      remain spatially distant in both native and oxidatively modified CaM, the
      oxidative modification of methionines in the carboxyl-terminal domain are
      suggested to modify the conformation of the amino-terminal domain through
      alterations in the structural features involving the interdomain central helix.
      The structural basis for the linkage between oxidative modification and these
      global conformational changes is discussed in terms of possible alterations in
      specific noncovalent interactions that have previously been suggested to
      stabilize the central helix in CaM.

PMID- 9512015
TI  - Low-temperature electron transfer from cytochrome to the special pair in
      Rhodopseudomonas viridis: role of the L162 residue.
AB  - Electron transfer from the tetraheme cytochrome c to the special pair of
      bacteriochlorophylls (P) has been studied by flash absorption spectroscopy in
      reaction centers isolated from seven strains of the photosynthetic purple
      bacterium Rhodopseudomonas viridis, where the residue L162, located between the
      proximal heme c-559 and P, is Y (wild type), F, W, G, M, T, or L. Measurements
      were performed between 294 K and 8 K, under redox conditions in which the two
      high-potential hemes of the cytochrome were chemically reduced. At room
      temperature, the kinetics of P+ reduction include two phases in all of the
      strains: a dominant very fast phase (VF), and a minor fast phase (F). The VF
      phase has the following t(1/2): 90 ns (M), 130 ns (W), 135 ns (F), 189 ns (Y;
      wild type), 200 ns (G), 390 ns (L), and 430 ns (T). These data show that electron
      transfer is fast whatever the nature of the amino acid at position L162. The
      amplitudes of both phases decrease suddenly around 200 K in Y, F, and W. The
      effect of temperature on the extent of fast phases is different in mutants G, M,
      L, and T, in which electron transfer from c-559 to P+ takes place at cryogenic
      temperatures in a substantial fraction of the reaction centers (T, 48%; G, 38%;
      L, 23%, at 40 K; and M, 28%, at 60 K), producing a stable charge separated state.
      In these nonaromatic mutants the rate of VF electron transfer from cytochrome to
      P+ is nearly temperature-independent between 294 K and 8 K, remaining very fast
      at very low temperatures (123 ns at 60 K for M; 251 ns at 40 K for L; 190 ns at 8
      K for G, and 458 ns at 8 K for T). In all cases, a decrease in amplitudes of the
      fast phases is paralleled by an increase in very slow reduction of P+, presumably
      by back-reaction with Q(A)-. The significance of these results is discussed in
      relation to electron transfer theories and to freezing at low temperatures of
      cytochrome structural reorganization.

PMID- 9512016
TI  - Cardiac Ca2+ dynamics: the roles of ryanodine receptor adaptation and
      sarcoplasmic reticulum load.
AB  - We construct a detailed mathematical model for Ca2+ regulation in the ventricular
      myocyte that includes novel descriptions of subcellular mechanisms based on
      recent experimental findings: 1) the Keizer-Levine model for the ryanodine
      receptor (RyR), which displays adaptation at elevated Ca2+; 2) a model for the L
      type Ca2+ channel that inactivates by mode switching; and 3) a restricted
      subspace into which the RyRs and L-type Ca2+ channels empty and interact via
      Ca2+. We add membrane currents from the Luo-Rudy Phase II ventricular cell model
      to our description of Ca2+ handling to formulate a new model for ventricular
      action potentials and Ca2+ regulation. The model can simulate Ca2+ transients
      during an action potential similar to those seen experimentally. The subspace
      [Ca2+] rises more rapidly and reaches a higher level (10-30 microM) than the bulk
      myoplasmic Ca2+ (peak [Ca2+]i approximately 1 microM). Termination of
      sarcoplasmic reticulum (SR) Ca2+ release is predominately due to emptying of the
      SR, but is influenced by RyR adaptation. Because force generation is roughly
      proportional to peak myoplasmic Ca2+, we use [Ca2+]i in the model to explore the
      effects of pacing rate on force generation. The model reproduces transitions seen
      in force generation due to changes in pacing that cannot be simulated by previous
      models. Simulation of such complex phenomena requires an interplay of both RyR
      adaptation and the degree of SR Ca2+ loading. This model, therefore, shows
      improved behavior over existing models that lack detailed descriptions of
      subcellular Ca2+ regulatory mechanisms.

PMID- 9512017
TI  - Motion of RNA polymerase along DNA: a stochastic model.
AB  - RNA polymerase is a key transcription enzyme that moves along a DNA double helix
      to polymerize an RNA transcript. Recent progress in micromechanical experiments
      permits quantitative studies of forces and motion generated by the enzyme. We
      present in this paper a chemical kinetics description of RNA polymerase motion.
      The model is based on a classical chemical kinetics description of polymerization
      reactions driven by a free energy gain that depends on forces applied externally
      at the catalytic site. The RNA polymerase controlled activation barrier of the
      reaction is assumed to be strongly dependent on inhibitory internal strains of
      the RNA polymerase molecule. The sequence sensitivity of RNA polymerase is
      described by a linear coupling between the height of the activation barrier and
      the local DNA sequence. Our model can simulate optical trap experiments and
      allows us to study the dynamics of chemically halted complexes that are important
      for footprinting studies. We find that the effective stall force is a sequence
      dependent, statistical quantity, whose distribution depends on the observation
      time. The results are consistent with the experimental observations to date.

PMID- 9512018
TI  - Force generation in RNA polymerase.
AB  - RNA polymerase (RNAP) is a processive molecular motor capable of generating
      forces of 25-30 pN, far in excess of any other known ATPase. This force derives
      from the hydrolysis free energy of nucleotides as they are incorporated into the
      growing RNA chain. The velocity of procession is limited by the rate of
      pyrophosphate release. Here we demonstrate how nucleotide triphosphate binding
      free energy can rectify the diffusion of RNAP, and show that this is sufficient
      to account for the quantitative features of the measured load-velocity curve.
      Predictions are made for the effect of changing pyrophosphate and nucleotide
      concentrations and for the statistical behavior of the system.

PMID- 9512019
TI  - Using experimental information to produce a model of the transmembrane domain of
      the ion channel phospholamban.
AB  - Molecular models of the transmembrane domain of the phospholamban pentamer have
      been generated by a computational method that uses the experimentally measured
      effects of systematic single-site mutations as a guiding force in the modeling
      procedure. This method makes the assumptions that 1) the phospholamban
      transmembrane domain is a parallel five-helix bundle, and 2) nondisruptive
      mutation positions are lipid exposed, whereas 3) disruptive or partially
      disruptive mutations are not. Our procedure requires substantially less computer
      time than systematic search methods, allowing rapid assessment of the effects of
      different experimental results on the helix arrangement. The effectiveness of the
      approach is investigated in test calculations on two helix-dimer systems of known
      structure. Two independently derived sets of mutagenesis data were used to define
      the restraints for generating models of phospholamban. Both resulting models are
      left-handed, highly symmetrical pentamers. Although the overall bundle geometry
      is very similar in the two models, the orientation of individual helices differs
      by approximately 50 degrees, resulting in different sets of residues facing the
      pore. This demonstrates how differences in restraints can have an effect on the
      model structures generated, and how the violation of these restraints can
      identify inconsistent experimental data.

PMID- 9512020
TI  - Theory for ligand rebinding at cell membrane surfaces.
AB  - Conditions for which a ligand reversibly bound to a cell surface dissociates and
      then rebinds to the surface have been theoretically examined. The coupled
      differential equations that describe reaction at the interface between sites on a
      plane and three-dimensional solution have been described previously (Thompson, N.
      L., T. P. Burghardt, and D. Axelrod. 1981. Biophys. J. 33:435-454). Here, we use
      this theoretical formalism to provide an analytical solution for the spatial and
      temporal dependence of the probabilities of finding a molecule on the surface or
      in the solution, given initial placement on the surface at the origin. This
      general analytical solution is used to derive a simple expression for the
      probability that a molecule rebinds to the surface at a given position and time
      after release at the origin and time zero. The probability expressions provide
      fundamental equations that form a basis for subsequent modeling of ligand
      receptor interactions in specific geometries.

PMID- 9512021
TI  - Bistability in the isocitrate dehydrogenase reaction: an experimentally based
      theoretical study.
AB  - The enzyme isocitrate dehydrogenase (IDH, EC 1.1.1.42) can exhibit activation by
      one of its products, NADPH. This activation is competitively inhibited by the
      substrate NADP+, whereas NADPH competes with NADP+ for the catalytic site.
      Experimental observations briefly presented here have shown that if IDH is
      coupled to another enzyme, diaphorase (EC 1.8.1.4), which transforms NADPH into
      NADP+, the system can attain either one of two stable states, corresponding to a
      low and a high NADPH concentration. The evolution toward either one of these
      stable states depends on the time of addition of diaphorase to the medium
      containing IDH and its substrate NADP+. We present a theoretical and numerical
      analysis of a model for the IDH-diaphorase bienzymatic system, based on the
      regulatory properties of IDH. The results confirm the occurrence of bistability
      for parameter values derived from the experiments. Depending on the total
      concentration of NADP+ plus NADPH and the concentration of IDH, the system can
      either admit a single steady state or display bistability. We obtain an
      expression for the critical time t*, before which diaphorase addition leads to
      the lower steady state and after which addition of the enzyme leads to the upper
      steady state of NADPH. The analysis is extended to the case where the second
      substrate of IDH, isocitrate, is consumed in the course of the reaction without
      being regenerated. Bistability occurs only as a transient phenomenon in these
      conditions.

PMID- 9512022
TI  - Calculation of electron transfer reorganization energies using the finite
      difference Poisson-Boltzmann model.
AB  - A description is given of a method to calculate the electron transfer
      reorganization energy (lambda) in proteins using the linear or nonlinear Poisson
      Boltzmann (PB) equation. Finite difference solutions to the linear PB equation
      are then used to calculate lambda for intramolecular electron transfer reactions
      in the photosynthetic reaction center from Rhodopseudomonas viridis and the
      ruthenated heme proteins cytochrome c, myoglobin, and cytochrome b and for
      intermolecular electron transfer between two cytochrome c molecules. The overall
      agreement with experiment is good considering both the experimental and
      computational difficulties in estimating lambda. The calculations show that
      acceptor/donor separation and position of the cofactors with respect to the
      protein/solvent boundary are equally important and, along with the overall
      polarizability of the protein, are the major determinants of lambda. In agreement
      with previous studies, the calculations show that the protein provides a low
      reorganization environment for electron transfer. Agreement with experiment is
      best if the protein polarizability is modeled with a low (<8) average effective
      dielectric constant. The effect of buried waters on the reorganization energy of
      the photosynthetic reaction center was examined and found to make a contribution
      ranging from 0.05 eV to 0.27 eV, depending on the donor/acceptor pair.

PMID- 9512023
TI  - Molecular modeling of the enantioselectivity in lipase-catalyzed
      transesterification reactions.
AB  - Two strategies based on the use of subsets for calculating the enantioselectivity
      in lipase-catalyzed transesterifications using the CHARMM force field were
      investigated. Molecular dynamics was used in our search for low energy
      conformations. Molecular mechanics was used for refining these low energy
      conformations. A tetrahedral intermediate with a rigid central part was used for
      mimicking the transition state. The energy differences between the transition
      states of the diastereomeric enzyme-substrate complexes were calculated. The way
      of defining the subsets was based on two fundamentally different strategies. The
      first strategy used predefined parts of the enzyme and the substrate as subsets.
      The second approach formed energy-based subsets, varying in size with the
      substrates studied. The selection of residues to be included in these energy
      based subsets was based on the energy of the interaction between the specific
      residue or water molecule and the transition state. The reaction studied was the
      kinetic resolution of secondary alcohols in transesterifications using the
      Candida antarctica lipase B as chiral biocatalyst. The secondary alcohols used in
      the study were 2-butanol, 3-methyl-2-butanol, and 3,3-dimethyl-2-butanol.

PMID- 9512024
TI  - Sulfhydryl oxidation modifies the calcium dependence of ryanodine-sensitive
      calcium channels of excitable cells.
AB  - The calcium dependence of ryanodine-sensitive single calcium channels was studied
      after fusing with planar lipid bilayers sarcoendoplasmic reticulum vesicles
      isolated from excitable tissues. Native channels from mammalian or amphibian
      skeletal muscle displayed three different calcium dependencies, cardiac (C),
      mammalian skeletal (MS), and low fractional open times (low Po), as reported for
      channels from brain cortex. Native channels from cardiac muscle presented only
      the MS and C dependencies. Channels with the MS or low Po behaviors showed bell
      shaped calcium dependencies, but the latter had fractional open times of <0.1 at
      all [Ca2+]. Channels with C calcium dependence were activated by [Ca2+] < 10
      microM and were not inhibited by increasing cis [Ca2+] up to 0.5 mM. After
      oxidation with 2,2'-dithiodipyridine or thimerosal, channels with low Po or MS
      dependencies increased their activity. These channels modified their calcium
      dependencies sequentially, from low Po to MS and C, or from MS to C. Reduction
      with glutathione of channels with C dependence (native or oxidized) decreased
      their fractional open times in 0.5 mM cis [Ca2+], from near unity to 0.1-0.3.
      These results show that all native channels displayed at least two calcium
      dependencies regardless of their origin, and that these changed after treatment
      with redox reagents.

PMID- 9512025
TI  - Effects of divalent cations on the E-4031-sensitive repolarization current,
      I(Kr), in rabbit ventricular myocytes.
AB  - The effects of divalent cations on the E-4031-sensitive repolarization current
      (I(Kr)) were studied in single ventricular myocytes isolated from rabbit hearts.
      One group of divalent cations (Cd2+, Ni2+, Co2+, and Mn2+) produced a rightward
      shift of the I(Kr) activation curve along the voltage axis, increased the maximum
      I(Kr) amplitude (i.e., relieved the apparent inward rectification of the
      channel), and accelerated I(Kr) tail current kinetics. Another group (Ca2+, Mg2+
      and Sr2+) had relatively little effect on I(Kr). The only divalent cation that
      blocked I(Kr) was Zn2+ (0.1-1 mM). Under steady-state conditions, Ba2+ caused a
      substantial block of I(K1) as previously reported. However, block by Ba2+ was
      time dependent, which precluded a study of Ba2+ effects on I(Kr). We conclude
      that the various effects of the divalent cations can be attributed to
      interactions with distinct sites associated with the rectification and/or
      inactivation mechanism of the channel.

PMID- 9512026
TI  - Asymmetrical distribution of Ca-activated Cl channels in Xenopus oocytes.
AB  - Xenopus oocytes are a popular model system for studying Ca signaling. They
      endogenously express two kinds of Ca-activated Cl currents, I(Cl-1), and I(Cl-2).
      I(Cl-1) is activated by Ca released from internal stores and, with appropriate
      voltage protocols, by Ca influx. In contrast, I(Cl-2) activation is dependent on
      Ca influx. We are interested in understanding how these two different Cl channels
      are activated differently by Ca from different sources. One could hypothesize
      that these channels are activated differently because they are differentially
      localized near the corresponding Ca source. As an initial investigation of this
      hypothesis, we examined the distribution of I(Cl-1) and I(Cl-2) channels in the
      oocyte. We conclude that both I(Cl-1) and (Cl-2) channels are primarily localized
      to the animal hemisphere of the oocyte, but that capacitative Ca influx occurs
      over the entire oocyte membrane. Evidence supporting this view includes the
      following observations: 1) Injection of IP3 into the animal hemisphere produced
      larger and faster I(Cl-1) responses than injection into the vegetal hemisphere.
      2) Exposure of the animal hemisphere to Cl-free solution almost completely
      abolished I(Cl-1) produced by IP3-induced release of Ca from internal stores or
      by capacitative Ca entry. 3) Loose macropatch recording showed that both I(Cl-1)
      and I(Cl-2) currents were approximately four times and approximately three times,
      respectively, more dense in the animal than in the vegetal hemisphere. 4)
      Confocal imaging of oocytes loaded with fluorescent Ca-sensitive dyes showed that
      the time course of activation of I(Cl-1) corresponded to the appearance of the
      wave of Ca release at the animal pole. 5) Ca release and Ca influx, although
      twofold higher in the animal pole, were evident over the entire oocyte.

PMID- 9512027
TI  - The interactions of ATP, ADP, and inorganic phosphate with the sheep cardiac
      ryanodine receptor.
AB  - The effects of ATP, ADP, and inorganic phosphate (Pi) on the gating of native
      sheep cardiac ryanodine receptor channels incorporated into planar phospholipid
      bilayers were investigated. We demonstrate that ATP and ADP can activate the
      channel by Ca2+-dependent and Ca2+-independent mechanisms. ATP and ADP appear to
      compete for the same site/s on the cardiac ryanodine receptor, and in the
      presence of cytosolic Ca2+ both agents tend to inactivate the channel at
      supramaximal concentrations. Our results reveal that ATP not only has a greater
      affinity for the adenine nucleotide site/s than ADP, but also has a greater
      efficacy. The EC50 value for channel activation is approximately 0.2 mM for ATP
      compared to 1.2 mM for ADP. Most interesting is the fact that, even in the
      presence of cytosolic Ca2+, ADP cannot activate the channel much above an open
      probability (Po) of 0.5, and therefore acts as a partial agonist at the adenine
      nucleotide binding site on the channel. We demonstrate that Pi also increases Po
      in a concentration and Ca2+-dependent manner, but unlike ATP and ADP, has no
      effect in the absence of activating cytosolic [Ca2+]. We demonstrate that Pi does
      not interact with the adenine nucleotide site/s but binds to a distinct domain on
      the channel to produce an increase in Po.

PMID- 9512028
TI  - Two blocking sites of amino-adamantane derivatives in open N-methyl-D-aspartate
      channels.
AB  - Using whole-cell patch-clamp techniques, we studied the blockade of open N-methyl
      D-aspartate (NMDA) channels by amino-adamantane derivatives (AADs) in rat
      hippocampal neurons acutely isolated by the vibrodissociation method. The rapid
      concentration-jump technique was used to replace superfusion solutions. A kinetic
      analysis of the interaction of AAD with open NMDA channels revealed fast and slow
      components of their blockade and recovery. Mathematical modeling showed that
      these kinetic components are evidence for two distinct blocking sites of AADs in
      open NMDA channels. A comparative analysis of different simplest models led us to
      conclude that these AAD blocking sites can be simultaneously occupied by two
      blocker molecules. The voltage dependence of the AAD block suggested that both
      sites were located deep in the channel pore.

PMID- 9512029
TI  - Cystic fibrosis transmembrane conductance regulator (CFTR) anion binding as a
      probe of the pore.
AB  - We compared the effects of mutations in transmembrane segments (TMs) TM1, TM5,
      and TM6 on the conduction and activation properties of the cystic fibrosis
      transmembrane conductance regulator (CFTR) to determine which functional property
      was most sensitive to mutations and, thereby, to develop a criterion for
      measuring the importance of a particular residue or TM for anion conduction or
      activation. Anion substitution studies provided strong evidence for the binding
      of permeant anions in the pore. Anion binding was highly sensitive to point
      mutations in TM5 and TM6. Permeability ratios, in contrast, were relatively
      unaffected by the same mutations, so that anion binding emerged as the conduction
      property most sensitive to structural changes in CFTR. The relative insensitivity
      of permeability ratios to CFTR mutations was in accord with the notion that anion
      water interactions are important determinants of permeability selectivity. By the
      criterion of anion binding, TM5 and TM6 were judged to be likely to contribute to
      the structure of the anion-selective pore, whereas TM1 was judged to be less
      important. Mutations in TM5 and TM6 also dramatically reduced the sensitivity of
      CFTR to activation by 3-isobutyl 1-methyl xanthine (IBMX), as expected if these
      TMs are intimately involved in the physical process that opens and closes the
      channel.

PMID- 9512031
TI  - Vectorially oriented monolayers of the cytochrome c/cytochrome oxidase
      bimolecular complex.
AB  - Vectorially oriented monolayers of yeast cytochrome c and its bimolecular complex
      with bovine heart cytochrome c oxidase have been formed by self-assembly from
      solution. Both quartz and Ge/Si multilayer substrates were chemical vapor
      deposited with an amine-terminated alkylsiloxane monolayer that was then reacted
      with a hetero-bifunctional cross-linking reagent, and the resulting maleimide
      endgroup surface then provided for covalent interactions with the naturally
      occurring single surface cysteine 102 of the yeast cytochrome c. The bimolecular
      complex was formed by further incubating these cytochrome c monolayers in
      detergent-solubilized cytochrome oxidase. The sequential formation of such
      monolayers and the vectorially oriented nature of the cytochrome oxidase was
      studied via meridional x-ray diffraction, which directly provided electron
      density profiles of the protein(s) along the axis normal to the substrate plane.
      The nature of these profiles is consistent with previous work performed on
      vectorially oriented monolayers of either cytochrome c or cytochrome oxidase
      alone. Furthermore, optical spectroscopy has indicated that the rate of binding
      of cytochrome oxidase to the cytochrome c monolayer is an order of magnitude
      faster than the binding of cytochrome oxidase to an amine-terminated surface that
      was meant to mimic the ring of lysine residues around the heme edge of cytochrome
      c, which are known to be involved in the binding of this protein to cytochrome
      oxidase.

PMID- 9512030
TI  - Functional co-assembly among subunits of cyclic-nucleotide-activated,
      nonselective cation channels, and across species from nematode to human.
AB  - Cyclic-nucleotide-activated, nonselective cation channels have a central role in
      sensory transduction. They are most likely tetramers, composed of two subunits
      (alpha and beta or 1 and 2), with the former, but not the latter, being able to
      form homomeric cyclic-nucleotide-activated channels. Identified members of this
      channel family now include, in vertebrates, the rod and cone channels mediating
      visual transduction and the channel mediating olfactory transduction, each
      apparently with distinct alpha- and beta-subunits. Homologous channels have also
      been identified in Drosophila melanogaster and Caenorhabditis elegans. By co
      expressing any combination of two alpha-subunits, or alpha- and beta-subunits, of
      this channel family in HEK 293 cells, we have found that they can all co-assemble
      functionally with each other, including those from fly and nematode. This finding
      suggests that the subunit members so far identified form a remarkably homogeneous
      and conserved group, functionally and evolutionarily, with no subfamilies yet
      identified. The ability to cross-assemble allows these subunits to potentially
      generate a diversity of heteromeric channels, each with properties specifically
      suited to a particular cellular function.

PMID- 9512032
TI  - Ionic transport in lipid bilayer membranes.
AB  - The current-voltage relationships of model bilayer membranes have been measured
      in various phospholipid systems, under the influence of both a gradient of
      potential and an ionic concentration, in order to describe the ion translocation
      through hydrated transient defects (water channels) across the bilayer formed
      because of lipid structure fluctuations and induced by temperature. The results
      have been analyzed in the light of a statistical rate theory for the transport
      process across a lipid bilayer, recently proposed by Skinner et al. (1993). In
      order to take into account the observed I-V curves and in particular the
      deviation from an ohmic behavior observed at high potential values, the original
      model has been modified, and a new version has been proposed by introducing an
      additional kinetic process. In this way, a very good agreement with the
      experimental values has been obtained for all of the systems we have investigated
      (dimyristoylphosphatidyl ethanolamine bilayers and mixed systems composed by
      dimyristoylphosphatidyl ethanolamine/dimyristoylphosphatidylcholine mixtures and
      dimyristoylphosphatidyl ethanolamine/phosphatidic acid dipalmitoyl mixtures). The
      rate constants governing the reactions at the bilayer interfaces have been
      evaluated for K+ and Cl- ions, as a function of temperature, from 5 to 35 degrees
      C and bulk ionic concentrations from 0.02 to 0.2 M. Finally, a comparison between
      the original model of Skinner and the modified version is presented, and the
      advantages of this new formulation are briefly discussed.

PMID- 9512033
TI  - Hydration of polyethylene glycol-grafted liposomes.
AB  - This study aimed to characterize the effect of polyethylene glycol of 2000
      molecular weight (PEG2000) attached to a dialkylphosphatidic acid
      (dihexadecylphosphatidyl (DHP)-PEG2000) on the hydration and thermodynamic
      stability of lipid assemblies. Differential scanning calorimetry, densitometry,
      and ultrasound velocity and absorption measurements were used for thermodynamic
      and hydrational characterization. Using a differential scanning calorimetry
      technique we showed that each molecule of PEG2000 binds 136 +/- 4 molecules of
      water. For PEG2000 covalently attached to the lipid molecules organized in
      micelles, the water binding increases to 210 +/- 6 water molecules. This
      demonstrates that the two different structural configurations of the PEG2000, a
      random coil in the case of the free PEG and a brush in the case of DHP-PEG2000
      micelles, differ in their hydration level. Ultrasound absorption changes in
      liposomes reflect mainly the heterophase fluctuations and packing defects in the
      lipid bilayer. The PEG-induced excess ultrasound absorption of the lipid bilayer
      at 7.7 MHz for PEG-lipid concentrations over 5 mol % indicates the increase in
      the relaxation time of the headgroup rotation due to PEG-PEG interactions. The
      adiabatic compressibility (calculated from ultrasound velocity and density) of
      the lipid bilayer of the liposome increases monotonically with PEG-lipid
      concentration up to approximately 7 mol %, reflecting release of water from the
      lipid headgroup region. Elimination of this water, induced by grafted PEG, leads
      to a decrease in bilayer defects and enhanced lateral packing of the phospholipid
      acyl chains. We assume that the dehydration of the lipid headgroup region in
      conjunction with the increase of the hydration of the outer layer by grafting PEG
      in brush configuration are responsible for increasing thermodynamic stability of
      the liposomes at 5-7 mol % of PEG-lipid. At higher PEG-lipid concentrations,
      compressibility and partial volume of the lipid phase of the samples decrease.
      This reflects the increase in hydration of the lipid headgroup region (up to five
      additional water molecules per lipid molecule for 12 mol % PEG-lipid) and the
      weakening of the bilayer packing due to the lateral repulsion of PEG chains.

PMID- 9512034
TI  - Interaction of gangliosides with proteins depending on oligosaccharide chain and
      protein surface modification.
AB  - By using neutron and synchrotron x-ray small-angle scattering techniques, we
      investigated the process of the complexation of gangliosides with proteins. We
      treated monosialoganglioside (G(M1)), disialoganglioside (G(D1a)), and a mixture
      of G(M1)/G(D1a). Proteins used were bovine serum albumins whose surfaces were
      modified with different sugars (deoxy-D-galactose, deoxy-L-fucose, deoxymaltitol,
      and deoxycellobiitol), which were used as model glycoproteins in a membrane. We
      found that the complexation of gangliosides with albumins greatly depends on the
      combination of ganglioside species and protein surface modification. With a
      varying protein/ganglioside ratio in a buffer solution at pH 7, the complexation
      of G(M1) or G(D1a) with albumins modified by monosaccharides appears to be less
      destructive for ganglioside aggregate structures in forming large complexes; the
      complexation of G(D1a) with the albumins modified by disaccharides induces the
      formation of complexes with a dimeric structure; and the complexation of G(M1)
      with albumins modified by disaccharides, to form small complexes, is very
      destructive. The present results show a strong dependence of the interaction
      between ganglioside and protein on the characteristics of the ganglioside and
      protein surface, which would relate to a physiological function of gangliosides,
      such as a function regulating the receptor activity of glycoproteins in a cell
      membrane.

PMID- 9512035
TI  - Hybrid bilayer membranes in air and water: infrared spectroscopy and neutron
      reflectivity studies.
AB  - In this report we describe the fabrication and characterization of a
      phospholipid/alkanethiol hybrid bilayer membrane in air. The bilayer is formed by
      the interaction of phospholipid with the hydrophobic surface of a self-assembled
      alkanethiol monolayer on gold. We have characterized the resulting hybrid bilayer
      membrane in air using atomic force microscopy, spectroscopic ellipsometry, and
      reflection-absorption infrared spectroscopy. These analyses indicate that the
      phospholipid added is one monolayer thick, is continuous, and exhibits molecular
      order which is similar to that observed for phospholipid/phospholipid model
      membranes. The hybrid bilayer prepared in air has also been re-introduced to
      water and characterized using neutron reflectivity and impedance spectroscopy.
      Impedance data indicate that when moved from air to water, hybrid bilayers
      exhibit a dielectric constant and thickness that is essentially equivalent to
      hybrid bilayers prepared in situ by adding phospholipid vesicles to alkanethiol
      monolayers in water. Neutron scattering from these samples was collected out to a
      wave vector transfer of 0.25 A(-1), and provided a sensitivity to changes in
      total layer thickness on the order of 1-2 A. The data confirm that the acyl chain
      region of the phospholipid layer is consistent with that observed for
      phospholipid-phospholipid bilayers, but suggest greater hydration of the
      phospholipid headgroups of HBMs than has been reported in studies of lipid
      multilayers.

PMID- 9512036
TI  - The adsorption of phloretin to lipid monolayers and bilayers cannot be explained
      by langmuir adsorption isotherms alone.
AB  - Phloretin and its analogs adsorb to the surfaces of lipid monolayers and bilayers
      and decrease the dipole potential. This reduces the conductance for anions and
      increases that for cations on artificial and biological membranes. The
      relationship between the change in the dipole potential and the aqueous
      concentration of phloretin has been explained previously by a Langmuir adsorption
      isotherm and a weak and therefore negligible contribution of the dipole-dipole
      interactions in the lipid surface. We demonstrate here that the Langmuir
      adsorption isotherm alone is not able to properly describe the effects of dipole
      molecule binding to lipid surfaces--we found significant deviations between
      experimental data and the fit with the Langmuir adsorption isotherm. We present
      here an alternative theoretical treatment that takes into account the strong
      interaction between membrane (monolayer) dipole field and the dipole moment of
      the adsorbed molecule. This treatment provides a much better fit of the
      experimental results derived from the measurements of surface potentials of lipid
      monolayers in the presence of phloretin. Similarly, the theory provides a much
      better fit of the phloretin-induced changes in the dipole potential of lipid
      bilayers, as assessed by the transport kinetics of the lipophilic ion
      dipicrylamine.

PMID- 9512037
TI  - Electron cryomicroscopy of bacteriorhodopsin vesicles: mechanism of vesicle
      formation.
AB  - We obtained vesicles from purple membrane of Halobacterium halobium at different
      suspension compositions (pH, electrolytes, buffers), following the procedure of
      Kouyama et al. (1994) (J. Mol. Biol. 236:990-994). The vesicles contained
      bacteriorhodopsin (bR) and halolipid, and spontaneously formed during incubation
      of purple membrane suspension in the presence of detergent octylthioglucoside
      (OTG) if the protein:OTG ratio was 2:1 by weight. The size distribution of the
      vesicles was precisely determined by electron cryomicroscopy and was found to be
      almost independent on the incubation conditions (mean radius 17.9-19 nm). The
      size distribution in a given sample was close to the normal one, with a standard
      deviation of approximately +/- 1 nm. During dialysis for removal of the
      detergent, the vesicles diminished their radius by 2-2.5 nm. The results allow us
      to conclude that the driving force for the formation of bR vesicles is the
      preferential incorporation of OTG molecules in the cytoplasmic side of the
      membrane (with possible preferential delipidation of the extracellular side),
      which creates spontaneous curvature of the purple membrane. From the size
      distribution of the vesicles, we calculated the elasticity bending constant, K(B)
      approximately 9 x 10(-20) J, of the vesicle wall. The results provide some
      insight into the possible formation mechanisms of spherical assembles in living
      organisms. The conditions for vesicle formation and the mechanical properties of
      the vesicles could also be of interest with respect to the potential
      technological application of the bR vesicles as light energy converters.

PMID- 9512038
TI  - Effect of substrate roughness on D spacing supports theoretical resolution of
      vapor pressure paradox.
AB  - The lamellar D spacing has been measured for oriented stacks of lecithin bilayers
      prepared on a variety of solid substrates and hydrated from the vapor. We find
      that, when the bilayers are in the L(alpha) phase near 100% relative humidity,
      the D spacing is consistently larger when the substrate is rougher than when it
      is smooth. The differences become smaller as the relative humidity is decreased
      to 80% and negligible differences are seen in the L(beta') phase. Our
      interpretation is that rough substrates frustrate the bilayer stack
      energetically, thereby increasing the fluctuations, the fluctuational repulsive
      forces, and the water spacing compared with stacks on smooth surfaces. This
      interpretation is consistent with and provides experimental support for a
      recently proposed theoretical resolution of the vapor pressure paradox.

PMID- 9512039
TI  - Effect of viscosity on mechanics of single, skinned fibers from rabbit psoas
      muscle.
AB  - Muscle contraction is highly dynamic and thus may be influenced by viscosity of
      the medium surrounding the myofilaments. Single, skinned fibers from rabbit psoas
      muscle were used to test this hypothesis. Viscosity within the myofilament
      lattice was increased by adding to solutions low molecular weight sugars
      (disaccharides sucrose or maltose or monosaccharides glucose or fructose). At
      maximal Ca2+ activation, isometric force (Fi) was inhibited at the highest solute
      concentrations studied, but this inhibition was not directly related to
      viscosity. Solutes readily permeated the filament lattice, as fiber diameter was
      unaffected by added solutes (except for an increased diameter with Fi < 30% of
      control). In contrast, there was a linear dependence upon 1/viscosity for both
      unloaded shortening velocity and also the kinetics of isometric tension
      redevelopment; these effects were unrelated to either variation in solution
      osmolarity or inhibition of force. All effects of added solute were reversible.
      Inhibition of both isometric as well as isotonic kinetics demonstrates that
      viscous resistance to filament sliding was not the predominant factor affected by
      viscosity. This was corroborated by measurements in relaxed fibers, which showed
      no significant change in the strain-rate dependence of elastic modulus when
      viscosity was increased more than twofold. Our results implicate cross-bridge
      diffusion as a significant limiting factor in cross-bridge kinetics and, more
      generally, demonstrate that viscosity is a useful probe of actomyosin dynamics.

PMID- 9512040
TI  - X-ray diffraction indicates that active cross-bridges bind to actin target zones
      in insect flight muscle.
AB  - We report the first time-resolved study of the two-dimensional x-ray diffraction
      pattern during active contraction in insect flight muscle (IFM). Activation of
      demembranated Lethocerus IFM was triggered by 1.5-2.5% step stretches (risetime
      10 ms; held for 1.5 s) giving delayed active tension that peaked at 100-200 ms.
      Bundles of 8-12 fibers were stretch-activated on SRS synchrotron x-ray beamline
      16.1, and time-resolved changes in diffraction were monitored with a SRS 2-D
      multiwire detector. As active tension rose, the 14.5- and 7.2-nm meridionals
      fell, the first row line dropped at the 38.7 nm layer line while gaining a new
      peak at 19.3 nm, and three outer peaks on the 38.7-nm layer line rose. The first
      row line changes suggest restricted binding of active myosin heads to the
      helically preferred region in each actin target zone, where, in rigor, two-headed
      lead bridges bind, midway between troponin bulges that repeat every 38.7 nm.
      Halving this troponin repeat by binding of single active heads explains the
      intensity rise at 19.3 nm being coupled to a loss at 38.7 nm. The meridional
      changes signal movement of at least 30% of all myosin heads away from their
      axially ordered positions on the myosin helix. The 38.7- and 19.3-nm layer line
      changes signal stereoselective attachment of 7-23% of the myosin heads to the
      actin helix, although with too little ordering at 6-nm resolution to affect the
      5.9-nm actin layer line. We conclude that stretch-activated tension of IFM is
      produced by cross-bridges that bind to rigor's lead-bridge target zones,
      comprising < or = 1/3 of the 75-80% that attach in rigor.

PMID- 9512041
TI  - Thin filament cooperativity as a major determinant of shortening velocity in
      skeletal muscle fibers.
AB  - The mechanism underlying the calcium sensitivity of the velocity of shortening of
      skeletal muscle fibers was investigated using a multiple shortening protocol:
      within a single contraction, skinned rabbit psoas fibers were made to shorten
      repetitively under a light load by briefly stretching back to their initial
      length at regular intervals. At saturating [Ca2+], the initial fast shortening
      pattern was repeated reproducibly. At submaximal [Ca2+], the first shortening
      consisted of fast and slow phases, but only the slow phase was observed in later
      shortenings. When the fibers were held isometric after the first shortening, the
      velocity of the second shortening recovered with time. The recovery paralleled
      tension redevelopment, implying a close relationship between the velocity and the
      number of the preexisting force-producing cross-bridges. However, this
      parallelism was lost as [Ca2+] was increased. Thus, the velocity was modified in
      a manner consistent with the cooperative thin filament activation by strong
      binding cross-bridges and its modulation by calcium. The present results
      therefore provide evidence that the thin filament cooperativity is primarily
      responsible for the calcium sensitivity of velocity. The effect of inorganic
      phosphate to accelerate the slow phase of shortening is also explained in terms
      of the cooperative activation.

PMID- 9512042
TI  - Reversible inactivation of myosin subfragment 1 activity by mechanical
      immobilization.
AB  - The Mg-ATPase activity of skeletal muscle myosin subfragment 1 (S1) is reversibly
      eliminated when it is aggregated by the force of osmotic pressure dehydration
      using polyethylene glycol (PEG). Several experiments indicate nucleotides bind
      aggregated S1, but the effects of binding are attenuated. Compared with S1 in
      solution, epsilonADP binds aggregated S1 with reduced affinity, and the bound
      epsilonADP fluorescence intensity is more effectively quenched by acrylamide.
      When ATP binds aggregated S1, the tryptophan intensity increases to only 50% of
      the solution level. Chemical cross-linking of cys-707 to cys-697 by p
      phenylenedimaleimide is less efficient for aggregated S1 x MgADP. The data are
      consistent with aggregated S1 being able to bind nucleotide but not being able to
      complete the usual conformation change(s) in response to binding. If S1 is kept
      from aggregating by increasing the ionic strength at the same osmotic pressure,
      its Mg-ATPase activity and ATP-induced tryptophan fluorescence intensity increase
      are normal. The combined data are consistent with an ATP hydrolysis mechanism in
      which S1 segmental motion is coupled to its enzymatic activity. In this model,
      segmental motion is mechanically constrained by aggregation; the constrained S1
      can bind ATP, but it cannot complete the hydrolysis mechanism.

PMID- 9512043
TI  - Stepwise dynamics of connecting filaments measured in single myofibrillar
      sarcomeres.
AB  - Single relaxed myofibrils of bumblebee flight muscle were subjected to motor
      imposed ramp-length changes. The image of the striations was projected onto a
      linear photodiode array, and sarcomere length was computed as the spacing between
      centroids of contiguous A-bands. Centroid position was determined by integrating
      the respective A-band intensity peak and computing the location at which the area
      on one side was equal to the other. The resulting trace of centroid to centroid
      span versus time was stepwise, with periods of rapid shortening alternating with
      periods of pause. An alternative nondiscrete sensor gave similar steps. If thick
      filament length remains constant, stepwise sarcomere length changes imply that
      length changes in the connecting filament must be stepwise. Thus, shortening of
      the connecting filament occurs as a sequence of discrete events rather than as a
      continuous event.

PMID- 9512044
TI  - Insertion of telomere repeat sequence decreases plasmid DNA condensation by
      cobalt (III) hexaammine.
AB  - Telomere repeat sequence (TRS) DNA is found at the termini of most eukaryotic
      chromosomes. The sequences are highly repetitive and G-rich (e.g., [C(1-3)A/TG(1
      3)]n for the yeast Saccharomyces cerevisiae) and are packaged into nonnucleosomal
      protein-DNA structures in vivo. We have used total intensity light scattering and
      electron microscopy to monitor the effects of yeast TRS inserts on in vitro DNA
      condensation by cobalt (III) hexaammine. Insertion of 72 bp of TRS into a 3.3-kb
      plasmid depresses condensation as seen by light scattering and results in a 22%
      decrease in condensate thickness as measured by electron microscopy. Analysis of
      toroidal condensate dimensions suggests that the growth stages of condensation
      are inhibited by the presence of a TRS insert. The depression in total light
      scattering intensity is greater when the plasmid is linearized with the TRS at an
      end (39-49%) than when linearized with the TRS in the interior (18-22%). Circular
      dichroism of a 95-bp fragment containing the TRS insert gives a spectrum that is
      intermediate between the A-form and B-form, and the anomalous condensation
      behavior of the TRS suggests a noncanonical DNA structure. We speculate that
      under conditions in which the plasmid DNA condenses, the telomeric insert assumes
      a helical geometry that is similar to the A-form and is incompatible with packing
      into the otherwise B-form lattice of the condensate interior.

PMID- 9512045
TI  - Vibrational spectrum of the lumi intermediate in the room temperature rhodopsin
      photo-reaction.
AB  - The vibrational spectrum (650-1750 cm(-1)) of the lumi-rhodopsin (lumi)
      intermediate formed in the microsecond time regime of the room-temperature
      rhodopsin (RhRT) photoreaction is measured for the first time using picosecond
      time-resolved coherent anti-Stokes Raman spectroscopy (PTR/CARS). The vibrational
      spectrum of lumi is recorded 2.5 micros after the 3-ps, 500-nm excitation of
      RhRT. Complementary to Fourier transform infrared spectra recorded at Rh sample
      temperatures low enough to freeze lumi, these PTR/CARS results provide the first
      detailed view of the vibrational degrees of freedom of room-temperature lumi
      (lumiRT) through the identification of 21 bands. The exceptionally low intensity
      (compared to those observed in bathoRT) of the hydrogen out-of-plane (HOOP)
      bands, the moderate intensity and absolute positions of C-C stretching bands, and
      the presence of high-intensity C==C stretching bands suggest that lumiRT contains
      an almost planar (nontwisting), all-trans retinal geometry. Independently, the
      944-cm(-1) position of the most intense HOOP band implies that a resonance
      coupling exists between the out-of-plane retinal vibrations and at least one
      group among the amino acids comprising the retinal binding pocket. The formation
      of lumiRT, monitored via PTR/CARS spectra recorded on the nanosecond time scale,
      can be associated with the decay of the blue-shifted intermediate (BSI(RT))
      formed in equilibrium with the bathoRT intermediate. PTR/CARS spectra measured at
      a 210-ns delay contain distinct vibrational features attributable to BSI(RT),
      which suggest that the all-trans retinal in both BSI(RT) and lumiRT is strongly
      coupled to part of the retinal binding pocket. With regard to the energy
      storage/transduction mechanism in RhRT, these results support the hypothesis that
      during the formation of lumiRT, the majority of the photon energy absorbed by
      RhRT transfers to the apoprotein opsin.

PMID- 9512046
TI  - Antifreeze proteins bind independently to ice.
AB  - It has been suggested that cooperative interactions between antifreeze proteins
      (AFPs) on the ice surfaces are required for complete inhibition of ice crystal
      growth. To test this hypothesis, a 7-kDa type III AFP was linked through its N
      terminus to thioredoxin (12 kDa) or maltose-binding protein (42 kDa). The
      resultant 20-kDa and 50-kDa fusion proteins were larger in diameter than free AFP
      and thus precluded any extensive AFP-AFP contacts on the ice surface. Both fusion
      proteins were at least as active as free AFP at virtually all concentrations
      tested. By these criteria, AFPs function independently of each other and do not
      require specific intermolecular interactions to bind tightly to ice.

PMID- 9512047
TI  - The susceptibility of pure tubulin to high magnetic fields: a magnetic
      birefringence and x-ray fiber diffraction study.
AB  - The orientational behavior of microtubules assembled in strong magnetic fields
      has been studied. It is shown that when microtubules are assembled in a magnetic
      field, they align with their long axis parallel to the magnetic field. The effect
      of several parameters known to affect the microtubule assembly are investigated
      with respect to their effect on the final degree of alignment. Aligned samples of
      hydrated microtubules suitable for low-resolution x-ray fiber diffraction
      experiments have been produced, and the results obtained from the fiber
      diffraction experiments have been compared with the magnetic birefringence
      experiments. Comparisons with earlier fiber diffraction work and small-angle x
      ray solution scattering experiments have been made.

PMID- 9512048
TI  - Specific interaction and two-dimensional crystallization of histidine tagged
      yeast RNA polymerase I on nickel-chelating lipids.
AB  - Nickel-chelating lipid monolayers were used to generate two-dimensional crystals
      from yeast RNA polymerase I that was histidine-tagged on one of its subunits. The
      interaction of the enzyme with the spread lipid layers was found to be imidazole
      dependent, and the formation of two-dimensional crystals required small amounts
      of imidazole, probably to select the specific interaction of the engineered tag
      with the nickel. Two distinct preparations of RNA polymerase I tagged on
      different subunits yielded two different crystal forms, indicating that the
      position of the tag determines the crystallization process. The orientation of
      the enzyme in both crystal forms is correlated with the location of the tagged
      subunits in a three-dimensional model which shows that the tagged subunits are in
      contact with the lipid layer.

PMID- 9512049
TI  - Low-frequency Raman spectra of lysozyme crystals and oriented DNA films: dynamics
      of crystal water.
AB  - We observed low-frequency Raman spectra of tetragonal lysozyme crystals and DNA
      films, with varying water content of the samples. The spectra are fitted well by
      sums of relaxation modes and damped harmonic oscillators in the region from
      approximately 1 cm(-1) to 250 cm(-1). The relaxation modes are due to crystal
      water, and the distribution of relaxation times is determined. In wet samples,
      the relaxation time of a small part of the water molecules is a little longer
      than that of bulk water. The relaxation time of a considerable part of the
      crystal water, which belongs mainly to the secondary hydration shell, is an order
      of magnitude longer than that of bulk water. Furthermore, the relaxation time of
      some water molecules in the primary hydration shell of semidry samples is shorter
      than we expected. Thus we have shown that low-frequency Raman measurements
      combined with properly oriented samples can give specific information on the
      dynamics of hydration water in the ps range. On the other hand, we concluded,
      based on polarized Raman spectra of lysozyme crystals, that the damped
      oscillators correspond to essentially intramolecular vibrational modes.

PMID- 9512050
TI  - Localized dynamic light scattering: a new approach to dynamic measurements in
      optical microscopy.
AB  - We present a new approach to probing single-particle dynamics that uses dynamic
      light scattering from a localized region. By scattering a focused laser beam from
      a micron-size particle, we measure its spatial fluctuations via the temporal
      autocorrelation of the scattered intensity. We demonstrate the applicability of
      this approach by measuring the three-dimensional force constants of a single bead
      and a pair of beads trapped by laser tweezers. The scattering equations that
      relate the scattered intensity autocorrelation to the particle position
      correlation function are derived. This technique has potential applications for
      measurement of biomolecular force constants and probing viscoelastic properties
      of complex media.

PMID- 9512051
TI  - Optical measurement of presynaptic calcium currents.
AB  - Measurements of presynaptic calcium currents are vital to understanding the
      control of transmitter release. However, most presynaptic boutons in the
      vertebrate central nervous system are too small to allow electrical recordings of
      presynaptic calcium currents (I(Ca)pre). We therefore tested the possibility of
      measuring I(Ca)pre optically in boutons loaded with calcium-sensitive
      fluorophores. From a theoretical treatment of a system containing an endogenous
      buffer and an indicator, we determined the conditions necessary for the
      derivative of the stimulus-evoked change in indicator fluorescence to report
      I(Ca)pre accurately. Matching the calcium dissociation rates of the endogenous
      buffer and indicator allows the most precise optical measurements of I(Ca)pre. We
      tested our ability to measure I(Ca)pre in granule cells in rat cerebellar slices.
      The derivatives of stimulus-evoked fluorescence transients from slices loaded
      with the low-affinity calcium indicators magnesium green and mag-fura-5 had the
      same time courses and were unaffected by changes in calcium influx or indicator
      concentration. Thus both of these indicators were well suited to measuring
      I(Ca)pre. In contrast, the high-affinity indicator fura-2 distorted I(Ca)pre. The
      optically determined I(Ca)pre was well approximated by a Gaussian with a half
      width of 650 micros at 24 degrees C and 340 micros at 34 degrees C.

PMID- 9512052
TI  - Relative microelastic mapping of living cells by atomic force microscopy.
AB  - The spatial and temporal changes of the mechanical properties of living cells
      reflect complex underlying physiological processes. Following these changes
      should provide valuable insight into the biological importance of cellular
      mechanics and their regulation. The tip of an atomic force microscope (AFM) can
      be used to indent soft samples, and the force versus indentation measurement
      provides information about the local viscoelasticity. By collecting force
      distance curves on a time scale where viscous contributions are small, the forces
      measured are dominated by the elastic properties of the sample. We have developed
      an experimental approach, using atomic force microscopy, called force integration
      to equal limits (FIEL) mapping, to produce robust, internally quantitative maps
      of relative elasticity. FIEL mapping has the advantage of essentially being
      independent of the tip-sample contact point and the cantilever spring constant.
      FIEL maps of living Madine-Darby canine kidney (MDCK) cells show that elasticity
      is uncoupled from topography and reveal a number of unexpected features. These
      results present a mode of high-resolution visualization in which the contrast is
      based on the mechanical properties of the sample.

PMID- 9512055
TI  - Consistency of microstructural modeling of micelles: letter concerning
      "thermotropic behavior and stability of monosialoganglioside micelles in aqueous
      solution".

PMID- 9512053
TI  - Mitochondrial calcium in relaxed and tetanized myocardium.
AB  - The elemental composition of rat cardiac muscle was determined with electron
      probe x-ray microanalysis (EPMA) of rapidly frozen papillary muscles and
      trabeculae incubated with ryanodine (1 microM) in either 1.2 or 10 mM [Ca2+]o
      containing solutions, paced at 0.6 Hz or tetanized at 10 Hz. Total mitochondrial
      calcium increased significantly, by 4.2 mmol/kg dry weight during a 7 s tetanus,
      only in muscles tetanized in the presence of 10 mM [Ca2+]o when cytoplasmic Ca2+
      is 1-4 microM (Backx, P. H., W.-D. Gao, M. D. Azan-Backx, and E. Marban. 1995.
      The relationship between contractile force and intracellular [Ca2+] in intact rat
      trabeculae. J. Gen. Physiol. 105:1-19). Comparison of total mitochondrial with
      free mitochondrial Ca2+ reported in the literature indicates that the total/free
      ratio is approximately 6000 at physiological or near-physiological levels of
      total mitochondrial calcium. Increases in free mitochondrial [Ca2+] consistent
      with regulation of mitochondrial enzymes should be associated with increases in
      total mitochondrial calcium detectable with EPMA. However, such increases in
      mitochondrial calcium occur only as the result of prolonged, unphysiological
      elevations of cytosolic [Ca2+].

PMID- 9512054
TI  - Green fluorescent protein as a noninvasive intracellular pH indicator.
AB  - It was found that the absorbance and fluorescence of green fluorescent protein
      (GFP) mutants are strongly pH dependent in aqueous solutions and intracellular
      compartments in living cells. pH titrations of purified recombinant GFP mutants
      indicated >10-fold reversible changes in absorbance and fluorescence with pKa
      values of 6.0 (GFP-F64L/S65T), 5.9 (S65T), 6.1 (Y66H), and 4.8 (T203I) with
      apparent Hill coefficients of 0.7 for Y66H and approximately 1 for the other
      proteins. For GFP-S65T in aqueous solution in the pH range 5-8, the fluorescence
      spectral shape, lifetime (2.8 ns), and circular dichroic spectra were pH
      independent, and fluorescence responded reversibly to a pH change in <1 ms. At
      lower pH, the fluorescence response was slowed and not completely reversed. These
      findings suggest that GFP pH sensitivity involves simple protonation events at a
      pH of >5, but both protonation and conformational changes at lower pH. To
      evaluate GFP as an intracellular pH indicator, CHO and LLC-PK1 cells were
      transfected with cDNAs that targeted GFP-F64L/S65T to cytoplasm, mitochondria,
      Golgi, and endoplasmic reticulum. Calibration procedures were developed to
      determine the pH dependence of intracellular GFP fluorescence utilizing ionophore
      combinations (nigericin and CCCP) or digitonin. The pH sensitivity of GFP
      F64L/S65T in cytoplasm and organelles was similar to that of purified GFP
      F64L/S65T in saline. NH4Cl pulse experiments indicated that intracellular GFP
      fluorescence responds very rapidly to a pH change. Applications of intracellular
      GFP were demonstrated, including cytoplasmic and organellar pH measurement, pH
      regulation, and response of mitochondrial pH to protonophores. The results
      establish the application of GFP as a targetable, noninvasive indicator of
      intracellular pH.

PMID- 9512056
TI  - Reproductive behavioral responsiveness to noradrenergic stimulation in developing
      guinea pigs.
AB  - The stimulatory effects of ovarian hormones on sexual receptivity in guinea pigs
      may be mediated by norepinephrine. Juvenile females rarely exhibit steroid
      induced receptivity and also respond poorly to the lordosis-enhancing action of
      alpha-noradrenergic receptor stimulation. This experiment was designed to chart
      the development of behavioral responsiveness to the alpha-noradrenergic agonist,
      clonidine, and to test the hypothesis that higher doses of estradiol and/or
      clonidine are required to stimulate lordosis in juvenile compared to adult guinea
      pigs. Ovariectomized females received estradiol benzoate (10 microg or 50 microg
      SC) 40-48 h before administration of clonidine (1 mg/kg or 5 mg/ kg IP) or saline
      at 14-17-day intervals. Regardless of treatment, few animals (0-36%) displayed
      lordosis at 20, 34, or 48 days of age. At 65 days of age, in both estradiol dose
      groups significantly more clonidine- (1 mg/kg) than saline-injected animals
      displayed lordosis (80-91 vs. 0-33%, respectively). Clonidine (5 mg/kg) was
      ineffective at all ages. These data do not support the hypothesis that behavioral
      responsiveness to alpha-noradrenergic receptor stimulation in immature females
      can be elicited by increasing the doses of estradiol and/or clonidine. These
      results suggest the occurrence of a maturational change in the neural systems
      governing noradrenergic involvement in steroid-induced sexual behavior in guinea
      pigs.

PMID- 9512057
TI  - The role of accumbens dopamine in lever pressing and response allocation: effects
      of 6-OHDA injected into core and dorsomedial shell.
AB  - Three experiments investigated the behavioral effects of injections of the
      neurotoxic agent 6-hydroxydopamine (6-OHDA) into the core or shell of the nucleus
      accumbens. In the first experiment, it was observed that injections of 6-OHDA
      into either core or shell had no significant effect on variable interval 30-s
      responding. In Experiment 2, responding on a fixed ratio 5 (FR5) schedule was
      impaired by 6-OHDA injections in the core, but not the shell. Rats with core
      injections of 6-OHDA showed significant alterations in the relative distribution
      of interresponse times, which were indicative of reductions in the maximal rate
      of responding and increases in the number of pauses. In the third experiment,
      rats were tested using a lever-pressing/chow-feeding procedure, in which a
      preferred food (Bioserve pellets) was available by pressing a lever on a FR5
      schedule, but a less preferred food (lab chow) was also available concurrently in
      the test chamber. Untreated rats usually pressed the lever at high rates to
      obtain the food pellets and ate little of the lab chow. After training, dopamine
      depletions were produced by injections of 6-OHDA directly into the core or
      dorsomedial shell subregions. Injections of 6-OHDA into the core significantly
      decreased lever pressing for food pellets, increased lab chow consumption, and
      decreased the relative amount of food obtained by lever pressing. Dorsomedial
      shell injections of 6-OHDA had no significant effects on either lever pressing or
      lab chow consumption. Neurochemical results indicate that injections of 6-OHDA in
      the shell produced substantial depletions in the shell that were somewhat
      selective; however, injections of 6-OHDA into the core tended to deplete both
      core and shell. Correlational analyses revealed that decreases in FR5 lever
      pressing were associated with dopamine levels in the core, but not the shell. The
      present results indicate that substantial depletions of dopamine in the
      dorsomedial shell are not sufficient for suppressing reinforced lever pressing,
      and indicate that dopamine depletions must include the core area to impair
      performance on these tasks. The lack of effect of accumbens dopamine depletions
      on VI30 responding are consistent with the notion that accumbens dopamine
      depletions affect responding on schedules that generate a high rate of responding
      (FR5), but not those that generate a moderate rate of responding (e.g., VI30 s).
      The results of the concurrent FR5/chow-feeding experiment indicate that rats with
      accumbens dopamine depletions remain directed towards the acquisition and
      consumption of food. These results suggest that dopamine in the core region of
      accumbens sets constraints upon the selection of food-related behaviors, and that
      core dopamine depletions alter the relative allocation of food-related responses.

PMID- 9512058
TI  - Ethanol modulates cocaine-induced behavioral change in inbred mice.
AB  - We recently conducted a study of the behavioral effects of combined cocaine and
      ethanol in genetically defined mice. Male and female C57BL/6 (B6) and DBA/2 (D2)
      were tested in an automated activity monitor on 2 consecutive days. On day 1, all
      animals received an IP injection of sterile saline and were placed into the
      activity monitor for 30 min. Behaviors measured were total distance traveled,
      stereotypy, nosepokes, and wall-seeking. On day 2, all animals were tested again
      for 15 min following injection of one of the following: saline, 10% v/v ethanol
      at 2.0 g kg(-1) or 2.0 g kg(-1) ethanol plus 5, 15, or 30 mg kg(-1) cocaine.
      Cocaine alone at the same doses was injected into separate groups of animals. For
      the B6 strain, the overall effect of ethanol was to reduce cocaine-induced
      locomotor stimulation; no consistent effect of ethanol on cocaine-induced
      locomotion was observed in D2 mice. Cocaine-induced inhibition of nosepokes in
      both strains and sexes was partially reversed by ethanol. Ethanol also partially
      reversed cocaine-elevated stereotypy in both strains and both sexes. In B6 mice,
      cocaine-increased wall seeking tended to be reversed by coadministration of
      ethanol, whereas no consistent pattern was observed in the D2s. Results from this
      study suggest that the several measures affected by cocaine (locomotor activity,
      stereotypy, exploration, thigmotaxis) were, in turn, differentially affected by
      concurrent treatment with ethanol. Furthermore, our results point to genetic
      based differences in ethanol's effects on cocaine-related behaviors. We address
      the implications for combined ethanol and cocaine use in humans.

PMID- 9512059
TI  - Prenatal cocaine, alcohol, and undernutrition differentially alter mineral and
      protein content in fetal rats.
AB  - Alcohol exposure and undernutrition during pregnancy have been associated with
      altered fetal body composition. Recent observations suggest that cocaine exposure
      during pregnancy may impair delivery of nutrients to the fetus and could thereby
      alter body growth and composition. Such effects are important because they can
      adversely influence physical and neural development. Consequently, we
      investigated the dose-dependent effects of cocaine on fetal body composition in
      an animal (rat) model and compared such effects with those caused by prenatal
      alcohol exposure and undernutrition. Pregnant Sprague-Dawley rats received either
      20, 30, 40, or 50 mg/kg cocaine HCl (SC) twice daily from gestation days 7
      through 19. Pair-fed (undernutrition) and untreated control groups and a group
      receiving 3.0 g/kg alcohol (PO) twice daily served as comparison groups (n = 11
      to 14/group). Females were sacrificed on gestation day 20. One male and one
      female fetus was removed from each dam. The fetuses were minced, dehydrated,
      defatted, and analyzed for content of protein and the minerals Zn, Ca, Fe, Mg, K,
      and Na. In terms of concentration per unit of fat-free dry solids, male fetuses
      in the cocaine groups showed significant decreases in protein compared to
      untreated controls (15+/-3 to 20+/-2 mg/g vs. 24+/-4 mg/g, p = 0.01). There was a
      significant treatment effect for Ca (p < 0.05), reflecting a trend for decreased
      Ca concentrations in the fetuses of the cocaine and undernutrition groups. Male
      fetuses in the alcohol group had significantly elevated Mg levels compared to
      male fetuses in the other groups (3.0+/-0.8 vs. 1.0+/-0.2 to 2.3+/-0.7 mg/g, p <
      0.05). There were some sex differences, with female fetuses having significantly
      lower concentrations of Mg, Fe, K, and higher protein concentrations than male
      fetuses. Although the effects were few and modest, these results suggest that
      prenatal cocaine, alcohol, and undernutrition can differentially alter fetal body
      weight and composition and, therefore, adversely influence fetal development.

PMID- 9512060
TI  - Evidence for a serotonin-mediated effect of cocaine causing vasoconstriction and
      herniated umbilici in chicken embryos.
AB  - Some of cocaine (COC)'s pathophysiological effects on exposed embryos likely
      result from its vasoconstrictive action, and serotonin2 (5-HT2) agonists such as
      dimethoxyiodophenylaminopropane (DOI) can mimic these effects. Infusions of COC
      (5 mg/kg/min) or DOI (0.5 mg/kg/min) for 15 min into chicken eggs with embryos on
      E15 caused a significant reduction in blood vessel diameters (14 and 30%,
      respectively). Pretreatment with the 5-HT2 antagonist ritanserin (RIT, 0.9 mg/kg)
      18-22 h earlier blocked the effect of COC and blocked or attenuated the effect of
      DOI. In separate groups of chicken embryos exposed to multiple injections of low
      doses of COC on E18, herniated umbilici were prominent in hatchlings. A single
      bolus injection of the same absolute amount of COC did not cause herniated
      umbilici. An additional experiment replicated the induction of herniated umbilici
      by multiple injections of COC and demonstrated the probable involvement of 5-HT2
      receptors because RIT blocked COC's ability to induce this anomaly. These data
      suggest that COC's vasoconstrictive effect, via 5-HT2 receptors, may play a
      mechanistic role in some adverse outcomes in embryos exposed to COC.

PMID- 9512061
TI  - Involvement of serotonin in the modulation of cocaine-induced locomotor activity
      in the rat.
AB  - The influence of serotonin (5-HT) antagonists and a selective serotonin reuptake
      inhibitor (SSRI) on cocaine-induced locomotor activity, rears, and head bobs was
      investigated in female Glaxo Wistar rats. The SSRI, fluoxetine (10 mg/kg), and
      the nonselective 5-HT agent, methysergide, at the dose range of 5 and 15 mg/kg
      enhanced the behaviors produced by cocaine (15 mg/kg) to a similar extent.
      Moreover, the potentiation of cocaine-induced locomotor activity, rears, and head
      bobs was even greater after the combined administration of methysergide ( 15
      mg/kg) and fluoxetine (10 mg/kg). In order to investigate a possible involvement
      of 5-HT1A receptors in the observed potentiation by methysergide and fluoxetine,
      the potent and selective 5-HT1A antagonist, WAY 100635, was used. WAY 100635 (0.1
      and 1.5 mg/kg) markedly reduced the behaviors induced by cocaine preceded by
      fluoxetine (10 mg/kg) and methysergide (5 and 15 mg/kg) pretreatment,
      respectively, suggesting an involvement of 5-HT1A receptors in the action of
      fluoxetine and methysergide on cocaine-induced behaviors. An attenuation of the
      fluoxetine-enhanced cocaine-induced behaviors was also observed after
      pretreatment with the 5-HT2A antagonist ketanserin (0.1 and 1.0 mg/kg).
      Coadministration of ketanserin (1.0 mg/kg) and WAY 100635 (1.5 mg/kg) resulted in
      the greatest blockade of the fluoxetine-enhanced cocaine-induced behaviors. The
      antagonists and the SSRI, fluoxetine, did not alter the behaviors in comparison
      to that of saline-treated animals. These results provide evidence for an
      involvement of 5-HT1A receptors in the enhancing effect of fluoxetine and
      methysergide on cocaine-induced locomotor activity, rears, and head bobs, and
      suggest a stimulatory action of methysergide at the 5-HT1A receptor. In addition,
      some of the actions may also be mediated by activation of the 5-HT2A receptor
      and/or inhibition of the 5-HT2C receptor.

PMID- 9512062
TI  - The effects of MK-801 on spatial working memory and within-session spatial
      learning.
AB  - The present study investigated the effects of the NMDA channel blocker MK-801
      (0.05, 0.10, and 0.15 mg/kg) on a task that allows for the assessment of both
      spatial working memory and within-session spatial learning. During the first
      trial of each day, subjects were shown the spatial location of a food reward on a
      six-arm radial-arm maze. During nine subsequent free-choice trials, subjects were
      reinforced for returning to that same spatial location. The location of the food
      reward varied across days. Thus, choosing correctly on any given trial required
      subjects to remember where food had been received during the previous trials of
      that day. The effects of MK-801 on working memory were assessed by analyzing the
      overall number of errors committed during the nine free-choice trials of each
      day. The effects of MK-801 on within-session learning were assessed by comparing
      the number of errors committed during the first three trials of each day to the
      number of errors committed during the last three trials of each day. Only the
      highest dose of MK-801 tested (0.15 mg/kg) impaired spatial working memory. No
      dose of MK-801 impaired the ability of subjects to acquire spatial information
      within a given session. The failure of MK-801 to impair within-session spatial
      learning stands in contrast to the well-known effects of MK-801 on spatial
      learning measured across days. Thus, when coupled with previous research, the
      findings of the present study further suggest that the NMDA receptor plays a role
      in the long-term, but not short-term, storage of spatial information.

PMID- 9512063
TI  - Study of the behavioral effects of bilateral nucleus accumbens lesions on
      amphetamine and apomorphine in adult cats.
AB  - The aim of the present work was to study the effects of three different types of
      bilateral lesions performed on the nucleus accumbens, upon the behaviors elicited
      in adult cats by parenteral administration of amphetamine and apomorphine, and to
      obtain an understanding of the functional role played by the cited structure. To
      this end, 10 cats received bilateral injections of 6-OHDA, 18 microg in each
      accumbens; 8 cats received a similar treatment with ibotenic acid (20 microg),
      and 11 cats were submitted to bilateral electrolytic damage. Before and after
      performing these lesions, in separate sessions, amphetamine (2.5 mg/kg SC) and
      apomorphine (2.0 mg/kg SC) were administered and their respective behaviors were
      compared. Besides, in a group of 10 cats, 6 of them were bilaterally injected
      with the above cited dose of 6-OHDA into the accumbens to determine dopamine
      concentration and the other four served as control. In three cats, ibotenic acid
      (20 microg) was unilaterally injected into the accumbens for histological
      analysis. The contralateral structure served as control. Finally, four cats were
      sham operated. The results obtained show that the accumbens in cats participates
      in locomotion, in stereotyped motor behaviors, and in emotional fear-like
      behavior. Its role in the production of motor behaviors apparently is not as
      important as has been reported in rodents.

PMID- 9512064
TI  - Effect of mu opioid receptor blockade on alcohol intake in rats bred for high
      alcohol drinking.
AB  - Beta-funaltrexamine (beta-FNA), a selective mu opioid receptor antagonist, when
      administered in doses of 10.0, 15.0, and 20.0 mg/kg b.wt., decreased alcohol but
      not water intake in a dose-dependent manner in rats selectively bred for high
      alcohol intake (HAD line). Beta-FNA also suppressed the intake of a saccharin
      solution containing alcohol without altering the intake of a similar solution
      without alcohol. The results suggest that beta-FNA may prove useful as a
      pharmacotherapeutic agent for the treatment of alcohol dependence. In a second
      study, pituitary beta-endorphin gene expression (proopiomelanocortin or POMC
      messenger ribonucleic acid-mRNA) was compared in another pair of rat lines
      selectively bred for high or low alcohol intake (alcohol-preferring or P and
      alcohol-nonpreferring or NP lines). A repeated alcohol challenge (1.0 g/kg
      b.wt./day, IP for 4 days) produced a greater increase in POMC mRNA in the
      anterior and neurointermediate lobes of the pituitary of P rats compared with NP
      rats. The results suggest that a genetic predisposition toward high alcohol
      drinking may be associated with increased responsiveness of the opioid system to
      alcohol.

PMID- 9512065
TI  - Distribution and clearance of cocaine in brain is influenced by genetics.
AB  - The purpose of this study was to examine the pharmacokinetics of cocaine in two
      inbred mouse strains, C57BL/6 (B6) and DBA/2 (D2). Male and female mice were
      administered 30 mg kg(-1) cocaine IP and killed after 5, 15, 30, or 60 minutes
      postinjection. Brains were removed quickly and assayed for total brain cocaine
      concentration. Quantification of cocaine was conducted using gas chromatography
      and mass spectrometry. The results of this study revealed a strain difference in
      total brain cocaine kinetics. Specifically, we observed that at 5 min onward, B6
      mice cleared cocaine from the brain with a t1/2 estimated at 22.3 min, while
      distribution in D2 mice appeared to be incomplete until 15 min with a subsequent
      t1/2 estimated at 11.2 min. These results show that despite faster clearance by
      D2 mice, the prolonged time to distribution in this strain may help explain why
      D2 mice show initial greater locomotor activation by cocaine, compared to B6s.

PMID- 9512066
TI  - Scopolamine-induced impairment in concurrent fixed-interval responding in a
      radial maze task.
AB  - The present study investigated the effects of scopolamine hydrobromide (SCOP:
      0.06-1.0 mg/kg IP) and its quartenary analogue, scopolamine methylbromide
      (SCOPMB), on performance in a radial arm maze foraging task, to dissociate
      general drug-induced alterations of motor performance from measurement of
      impairments on more complex behaviors involving timing and memory. In this
      paradigm. rats are trained to free run a radial maze under an eight-alternative
      concurrent fixed-interval (FI) schedule of food reinforcement. The eight FIs (55
      to 759 s) were assigned randomly to the arms of the maze, with a different
      pattern for each animal. SCOP produced dose-dependent degradation in response
      patterning and response rates in the concurrent FI schedules without
      significantly affecting the rates of arm entries or arm traversal latencies. The
      peripheral cholinergic antagonist, SCOPMB, generally produced small to moderate
      depressions in all measures with the exception of patterning of arm entries and
      pellets earned, but there were no clear dose-response relationships evident in
      the data. These results are consistent with the notion that central cholinergic
      mechanisms are involved in the mediation of complex conditioned behaviors.

PMID- 9512067
TI  - Cocaine and alcohol synergism in taste aversion learning.
AB  - Female Long-Evans rats were given 20-min access to saccharin followed by
      injections of alcohol and cocaine, alone and in combination. Although there was
      no significant interaction between alcohol and cocaine when cocaine was given
      intraperitoneally (IP), aversions induced by the drug combination when cocaine
      was administered subcutaneously (SC) were significantly greater than those
      induced by either drug alone. Further, the aversions induced by the combination
      were significantly greater than the summed effects of the individual drugs
      administered alone, indicating a synergistic interaction between cocaine and
      alcohol. It was suggested that this synergism might result from a summation of
      the effects of alcohol, cocaine, and cocaethylene, a unique and toxic metabolite
      of cocaine produced when alcohol is coadministered. To assess the role of
      cocaethylene in the present design, additional taste aversion assessments were
      performed in which saccharin was paired with either IP or SC injections of
      cocaethylene. Although cocaethylene was found to induce aversions, the summed
      changes in consumption from baseline produced by cocaine, alcohol, and
      cocaethylene were significantly less than the changes produced by cocaine and
      alcohol in combination. These results indicate that the synergistic interaction
      between cocaine and alcohol in the present design cannot be attributed solely to
      summation of the effects of the individual drugs and the metabolite cocaethylene.
      Additional mechanisms by which cocaethylene might contribute to the synergistic
      interaction between cocaine and alcohol, as well as the role pharmacokinetic
      interactions between cocaine and alcohol might have in the interaction, were
      discussed.

PMID- 9512068
TI  - Antagonism by abecarnil of enhanced acetylcholine release in the rat brain during
      anticipation but not consumption of food.
AB  - Changes in the extracellular concentration of acetylcholine (ACh) were evaluated
      in the prefrontal cortex and hippocampus of freely moving rats habituated for 35
      days to consume their daily meal during a fixed 2-h period. During the 40 min
      immediately before presentation, ACh output increased by 49 and 55% in the
      prefrontal cortex and hippocampus, respectively. ACh release increased further
      during the first 40 min of consumption phase in the prefrontal cortex (+220%) and
      hippocampus (175%). Administration of abecarnil (0.1 mg/kg, IP) 40 min before
      food presentation prevented the increase in ACh output in both brain regions
      during the anticipatory phase. In contrast, although abecarnil reduced the ACh
      content achieved during the consummatory phase, it did not prevent the increase
      in ACh release in the prefrontal cortex or hippocampus induced by food intake.
      Finally, the binding of [35S]TPBS to cerebral cortex, hippocampus, or septum of
      rats killed 20 min before food presentation was significantly higher than the
      values for animals killed 2 h after food presentation. These results suggest that
      during ingestive behavior ACh release is regulated by at least two independent
      mechanisms: one, associated with the anticipatory phase, that is sensitive to the
      activation of GABA(A) receptors. and a second, associated with the consummatory
      phase, that is insensitive to abecarnil.

PMID- 9512069
TI  - Effects of chlordiazepoxide on opioid-induced antinociception and respiratory
      depression in restrained rats.
AB  - This study investigates the influence of possible stress due to housing in Bolman
      cages on antinociception and on respiratory depression following opioid
      administration. To evaluate the functional role of this stressor and to modulate
      it, rats were subcutaneously pretreated with the anxiolytic chlordiazepoxide
      (CDP; 10 mg/kg) or saline (SAL) before the immobilization in the Bolman cages and
      before the intravenous administration of small doses of morphine (MOR),
      sufentanil (SUF), or vehicle (VEH). Antinociception, respiratory impairment and
      stress were evaluated by means of the tail-flick latency, blood gas analysis, and
      serum corticosterone (CS), adrenocorticotropic hormone (ACTH), and prolactin
      (PRL) determinations. The results demonstrated that 10 mg/kg CDP did not alter
      the antinociceptive effects of low doses of morphine and sufentanil. CDP
      pretreatment differentially affected the various blood gas parameters. Compared
      to vehicle pretreatment, there was a larger decrease in PaO2 following MOR and
      SUF in the CDP-pretreated rats. The effects were most pronounced at the lowest
      doses of both opioids. A CDP potentiation was also observed for the short-lasting
      raises in PaCO2 with the lowest concentrations of the opioids. At higher
      concentrations of the opioids, CDP was without any effect. With regard to the
      stress hormones, immobilization and an intravenous injection resulted in
      increases in CS and PRL in both CDP- and VEH-pretreated rats. ACTH did not change
      in these controls. SUF prevented the CS raises independent of a CDP pretreatment,
      while ACTH only increased in the SUF plus CDP groups, pointing to a stress
      reducing effect of SUF. Also, MOR without CDP prevented the increases in CS, but
      the opioid intrinsically increased ACTH. These results indicate that restraint in
      Bolman cages in the present setup, with animals recovering for several hours in
      these cages after being equipped with an arterial catheter, is stressful but
      without any significant effect on the opioid-induced antinociception.
      Pretreatment with an anxiolytic benzodiazepine only minimally affected the
      outcome of the opioids on respiratory depression and pointed to a stress-reducing
      effect of low doses of the opioids, especially sufentanil.

PMID- 9512070
TI  - Effect of extract of Rhazya stricta, a traditional medicinal plant, on rat brain
      tribulin.
AB  - Rhazya stricta leaves, which have both antidepressant and sedative properties in
      animal models, are widely used in folk medicine in the Arabian peninsula. In this
      study, the effects of oral administration of leaf extracts on rat brain tribulin
      levels [endogenous monoamine oxidase (MAO) A and B inhibitory activity], were
      determined. In an acute study, low doses brought about an increase in MAO A
      inhibitory activity, while intermediate doses caused a significant reduction. The
      highest doses had no significant effects on activity. There were no significant
      effects on MAO B inhibitory activity at any dose. Subchronic administration (21
      days) caused a significant decrease in MAO A inhibitory activity, most prominent
      at low dosage, and an increase in MAO B inhibitory activity. Acute intramuscular
      administration also resulted in a similar pattern. Such paradoxical effects were
      at least partially explained when different extracts of the leaves were used; a
      weakly basic chloroform fraction caused an increase in MAO A inhibitory activity,
      whereas butanol extracts brought about a decrease. These fractions had no
      significant effects on MAO B inhibitory activity. The findings show that Rhazya
      stricta leaves contain at least two different components that affect MAO
      inhibitory activity in opposite directions. It may be that the antidepressant and
      sedative actions of the plant are explicable in terms of these different
      components.

PMID- 9512071
TI  - Pharmacological evaluation of a modified open-field test sensitive to anxiolytic
      drugs.
AB  - In a recent study it has been shown that benzodiazepine receptor agonists
      attenuate novelty-induced suppression of feeding and increase the percentage of
      animals feeding in the open field. Food-deprived rats were placed in one corner
      of the open field containing food in the center. The number of rats beginning to
      eat in the first 5 min was recorded. In the present study this test was validated
      pharmacologically using known "anxiolytic" or "nonanxiolytic" drugs. The
      following substances (effective doses, given IP) increased the number of rats
      feeding within 5 min in the center of the open field: meprobamate (30.0-300
      mg/kg), 8-OH-DPAT (10 and 30 microg/kg), ipsapirone (1.0 and 2.0 mg/kg),
      ritanserin (0.125-0.5 mg/kg), tropisetron (0.1-10.0 microg/kg), ondansetron (0.3
      3.0 microg/kg), lisuride (0.28-0.55 mg/kg), morphine (0.3 and 1.0 mg/kg),
      propranolol (0.3 and 1.0 mg/kg), clozapine (1.0 mg/kg). Drugs without
      "anxiolytic" effects in other animal models or in humans, including amphetamine,
      apomorphine, haloperidol, sulpiride, and mCPP did not increase the incidence of
      food intake in this test. Ethanol and hexobarbital, in nonsedative doses, had no
      effect in this paradigm. Drugs and doses effective in the modified open-field
      test caused no increase in food intake in an independent food consumption test
      using food-deprived rats staying in the familiar cages. The results suggest that
      the modified open-field test can detect "anxiolytic" drug properties and is valid
      for the assessment of "anxiolytic" effects from different classes of drugs.

PMID- 9512072
TI  - The effect of baclofen and AP-7 on selected behavior in rats.
AB  - Synaptic plasticity, cognitive performance, learning, and memory appear to be
      determined by the balance between GABAergic inhibitory and glutaminergic
      excitatory amino acids (EAA). To evaluate this role of amino acids the effects of
      baclofen (0.5 mg/kg IP), GABA-B receptor agonist and AP-7 (5 nmol ICV)-NMDA (N
      methyl-D-aspartate) receptor antagonist on the processes of retrieval,
      consolidation of conditioned reflexes, object recognition, and locomotor activity
      were tested in rats. Neither AP-7 nor baclofen alone changed locomotor activity,
      but coadministration of AP-7 and baclofen significantly decreased this activity
      in the open-field test. Neither AP-7 nor baclofen influenced retrieval or
      consolidation in the passive avoidance situation when administered alone.
      Significantly prolonged retrieval and consolidation were observed when AP-7 and
      baclofen were given together. We did not find differences in effects of either AP
      7 or baclofen on object recognition, regardless whether administered alone or in
      combination.

PMID- 9512073
TI  - Discriminative stimulus effects of glutamate release inhibitors in rats trained
      to discriminate ethanol.
AB  - In a drug discrimination paradigm with rats trained to discriminate ethanol (1
      g/kg IP) from saline we studied two substances, lamotrigine and riluzole, which
      are regarded as glutamate release inhibitors concerning their ability to
      substitute for ethanol. Both substances have been shown to act primarily on
      voltage-gated sodium channels; however, Lamotrigine dose dependently generalized
      to the ethanol cue, whereas riluzole did not. These results reflect the different
      high-dose effects of both sustances at voltage-gated calcium channels, where
      lamotrigine has inhibitory effects, but not riluzole, and provide further
      evidence for a role of voltage-gated calcium channels in the mediation of the
      effects of ethanol.

PMID- 9512074
TI  - Gamma-hydroxybutyric acid decreases intravenous cocaine self-administration in
      rats.
AB  - Gamma-hydroxybutyric acid (GHB) is an endogenous compound present in mammalian
      brain suggested as a putative neurotransmitter, which has been shown to affect
      several aspects of dependence from various classes of drugs of abuse. In the
      present study, two sets of experiments were performed to investigate the effects
      of acute pretreatment with GHB on intravenous cocaine self-administration in
      rats. In the first experiment GHB was administered intragastrically at the doses
      of 175, 350, and 700 mg/kg to Long-Evans rats trained to self-administer cocaine
      using nose-poke as operandum. In the second experiment, GHB was administered
      intraperitoneally at the doses of 100, 200, and 400 mg/kg to Wistar rats trained
      to self-administer cocaine intravenously using lever-pressing as operandum. In
      both experiments acute pretreatment with GHB significantly and dose dependently
      reduced cocaine self-administration. The effectiveness of GHB was similar in both
      experiments, indicating that the effect of GHB on cocaine self-administration is
      independent of animal strain. route of administration, and type of operant
      response required. These results indicate that GHB reduces cocaine-seeking
      behavior in rats, modulating the acute reinforcing effect of cocaine. The
      clinical effectiveness of GHB in dependence from various classes of abused drugs
      warrants further studies to evaluate the possibility that GHB might represent a
      useful therapeutic agent for cocaine addiction in humans.

PMID- 9512075
TI  - The role of the nitric oxide (NO) pathway in the discriminative stimuli of
      amphetamine and cocaine.
AB  - To examine the role of the nitric oxide (NO) pathway in the stimulus effects
      induced by some psychostimulants, separate groups of rats were trained to
      discriminate between amphetamine (AMPH; 0.5 mg/kg) and saline, or cocaine (COC; 5
      mg/kg) and saline using a standard two-lever operant procedure. Substitution
      studies showed that AMPH and COC generalized for the training drugs in a dose
      dependent manner, their ED50, values being 0.1 mg/kg and 1.2 mg/kg, respectively.
      The dose-response function of both those psychostimulants did not change in the
      course of the experiment. Moreover, AMPH and COC induced cross-substitution
      effects towards each other. Successive combination tests demonstrated that
      injection of a fixed dose of the NO synthase (NOS) inhibitor 7-nitro indazole (7
      NI; 25 mg/kg) plus different doses of AMPH or COC resulted in a leftward shift in
      the dose-response curves of those psychostimulants and a decrease in their ED50
      values. On the other hand, pretreatment with the NO donor molsidomine (MOL),
      injected in a fixed dose of 100 mg/kg before AMPH and COC, shifted the dose
      response curves of the psychostimulants to the right and increased their ED50
      values. Our results indicate that NO plays an inhibitory role in the dopamine
      (DA)-evoked discrimination effects of AMPH and COC in rats.

PMID- 9512076
TI  - Indan analogs of fenfluramine and norfenfluramine have reduced neurotoxic
      potential.
AB  - N-Ethyl-5-trifluoromethyl-2-aminoindan (ETAI) and 5-trifluoromethyl-2-aminoindan
      (TAI) were synthesized to examine the effects of side-chain cyclization on the
      pharmacology of the anorectic drugs fenfluramine (FEN) and norfenfluramine
      (norFEN), respectively. ETAI and TAI inhibited synaptosomal accumulation of 5-HT
      but were less effective at inhibiting catecholamine uptake than FEN or norFEN,
      respectively. In vivo, ETAI and TAI were less neurotoxic than FEN or norFEN;
      decreases in the number of [3H]paroxetine-labeled 5-HT uptake sites were 50% less
      than the decreases produced by FEN or norFEN. Rats treated with ETAI. TAI, FEN,
      and norFEN lost 10-15% of their pretreatment body weight over a 4-day period,
      while saline-treated control animals gained 8%. In two-lever drug discrimination
      (DD) assays in rats, TAI fully substituted for the 5-HT releaser/uptake
      inhibitor, (+)-MBDB [(+)-N-methyl-1-(1,3-benzodioxol-5-yl)-2-aminobutane]. ETAI
      produced only partial substitution in this test. Neither TAI nor ETAI mimicked
      (+)-amphetamine in the DD assay. These studies demonstrate that incorporation of
      the side-chain of phenylisopropylamines into the five-membered ring of a 2
      aminoindan changes both the molecular pharmacology and the neurotoxic profile of
      FEN and norFEN, but does not diminish the drugs' ability to reduce body weight.

PMID- 9512077
TI  - Effects of acute or prolonged administration of cabergoline on parkinsonism
      induced by MPTP in common marmosets.
AB  - The effects of a single treatment or chronic administration of cabergoline (1-[(6
      allylergolin-8beta-yl)carbonyl]-1-[3-(dimethylamino)p ropyl]-3-ethyl-urea), a
      potent, long-lasting dopamine receptor agonist, on parkinsonism induced by 1
      methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in common marmosets were
      studied. The administration of 0.2 mg/kg or a higer dose of cabergoline began to
      reverse parkinsonism-like symptoms 60 min after a subcutaneous injection, and
      showed steady and constant effects throughout the observation period. For
      prolonged administration, 0.2 mg/kg cabergoline was injected daily for 22
      consecutive days. Locomotor activity in MPTP-treated animals increased until it
      reached its peak on the third day, then it gradually decreased. Akinesia scores,
      rating the quality of movements, were also improved, and the improvement was
      sustained up to the last day of chronic administration. None of the animals
      developed abnormal behaviors after either acute or chronic administration. These
      results suggest that cabergoline has long-acting effects in the marmoset model of
      parkinsonism, and that it will be a useful agent for the treatment of Parkinson's
      disease, particularly in cases with fluctuating motor disabilities.

PMID- 9512078
TI  - Differential involvement of opioid receptors in intrathecal butorphanol-induced
      analgesia: compared to morphine.
AB  - The present experiments were performed to investigate the differential
      involvement of the opioid receptor subtypes in the antinociception of intrathecal
      (IT) butorphanol compared to IT morphine. A single dose (26 nmol) of IT nor
      binaltorphimine (nor-BNI), beta-funaltrexamine (beta-FNA), and naltrindole (NTI)
      demonstrated a significant attenuation in the overall antinociception of IT
      butorphanol (52 nmol) or IT morphine (26 nmol). However, IT butorphanol elicits
      thermal antinociceptive effect through kappa > delta > or = mu, whereas morphine
      acts on mu >delta >> kappa. These results indicate that the antinociceptive
      effect of both IT butorphanol and IT morphine are mediated through mu, delta, and
      kappa opioid receptors in different relative orders.

PMID- 9512079
TI  - Effects of the serotonin agonists 8-OH-DPAT, buspirone, and DOI on water maze
      performance.
AB  - We have previously reported that the serotonin 5-HT1A agonist 8-OH-DPAT and the 5
      HT2c agonist TFMPP impair performance on a water maze. In the present report we
      extended those studies by examining a second 5-HT1A agonist, buspirone, to see
      whether its effects paralleled those of 8-OH-DPAT, and by testing the effects of
      the 5-HT2 agonist DOI. Unlike the open pool Morris water maze, the maze used in
      these experiments has alleys and doorways. The maze can be easily reconfigured to
      present rats with both previously learned or new maze challenges. Performance is
      assessed by time to reach the maze exit platform and the number of wrong doorways
      entered (errors). At doses that did not affect performance in a previously
      learned maze, the 5-HT1A agonists 8-OH-DPAT (0.1 mg/kg) and buspirone (1 mg/kg)
      slowed acquisition of a new maze configuration as measured by both swim time to
      the exit platform and errors committed. A higher dose of buspirone (10 mg/kg)
      completely blocked acquisition of a novel maze. In contrast. DOI slowed
      performance as assessed by swim time on both a well-learned maze as well as
      acquisition of a new maze, but did not affect error rate on either task,
      suggesting that this 5-HT2 agonist impaired performance by depressing motor
      activity. These experiments demonstrate that serotonin agonists, especially the 5
      HT1A subtype, can impair learning.

PMID- 9512080
TI  - Dopamine depletion in nucleus accumbens influences locomotion but not force and
      timing of operant responding.
AB  - This experiment examined the role of dopamine (DA) in the nucleus accumbens in
      regulating beam pressing and locomotor responses. Six rats were rewarded with
      sucrose on a partial reinforcement schedule for pressing force-sensitive beams.
      Open-field locomotor activity, and the force and timing characteristics of
      operant motor responses were recorded. It is known that low doses of apomorphine
      decrease DA tone through activating DA autoreceptors, resulting in suppression of
      both operant responses and locomotion. Our results showed that DA depletion in
      the nucleus accumbens, induced by bilateral injection of 6-hydroxydopamine, did
      not affect the force and timing of operant responses: neither did it reverse the
      suppressive effects of low doses of apomorphine on the force and timing of
      operant responses. However, accumbens DA depletion did block the suppressive
      effect of apomorphine on open-field locomotion. These results were interpreted as
      support for the hypothesis that the suppressive effects of low doses of
      apomorphine on locomotion, but not on operant beam pressing, are mediated mainly
      by DA autoreceptors in the mesolimbic pathway.

PMID- 9512081
TI  - Apomorphine-induced aggressiveness and [3H]citalopram binding after
      antidepressant treatment in rats.
AB  - The effects of acute and repeated administration of antidepressive drugs on
      apomorphine-induced aggressive behavior and [3H]citalopram binding were studied.
      In acute behavioral experiments with apomorphine pretreated (1.0 mg/kg, once
      daily) animals, desipramine (10 mg/kg) and clomipramine (10 mg/kg) enhanced,
      buspirone (2.5 and 5.0 mg/kg) completely blocked, but fluoxetine, amitriptyline,
      imipramine (10 mg/kg), and citalopram (10 and 20 mg/kg) had no effect on the
      intensity of aggressive behavior. Repeated concomitant apomorphine (1.0 mg/kg)
      and citalopram (10 mg/kg) administration reduced the affinity (Kd) of the 5-HT
      transporter binding sites in three brain regions. This finding was confirmed by
      an additional experiment as the effect of citalopram treatment. Repeated
      apomorphine (1.0 mg/kg) or apomorphine (1.0 mg/kg) plus desipramine (10 mg/kg)
      treatment had no unidirectional effect on Kd, the maximal number of apparent
      binding sties (Bmax) was unchanged in all experiments. Our study indicates that
      the 5-HT reuptake blockade has no major influence on the apomorphine-induced
      aggressive behavior, but the 5-HT1A receptor subtype may be involved in the
      mediation of the aggressive behavior in this paradigm.

PMID- 9512082
TI  - The blockade of H1 receptors attenuates the suppression of feeding and diuresis
      induced by inhibition of histamine catabolism.
AB  - Metoprine elevates brain histamine content by blocking the conversion of
      histamine to methylhistamine. It suppresses food intake, increases water intake.
      and induces diuresis in rats. In the present experiment, to study which receptors
      were involved in these metoprine-induced changes, H1, H2, and H3 receptor
      blockers were administered to metoprine (10 mg/kg IP)-treated rats. The food and
      water consumption and urine excretion were measured at 10 and 24 h after the drug
      administration. It was found that systemic administration of the H3 receptor
      antagonist, thioperamide (5 mg/kg IP), supplemented the feeding suppressive
      effect of metoprine. In addition to this, the H1 receptor antagonist mepyramine
      (20 mg/kg IP) antagonized the suppression of feeding in metoprine-treated rats,
      whereas the H2 receptor antagonist, ranitidine (100 mg/kg IP), had no effect.
      Mepyramine also decreased the diuretic response to metoprine, whereas ranitidine
      or thioperamide were virtually without effect. The present results show that
      elevation of brain histamine content by inhibiting the catabolism of histamine
      suppresses food intake, and this effect of metoprine can be abolished by
      pretreatment with antihistamines. Although the blockade of H1 receptors also
      attenuates the diuretic response to metoprine, further studies are needed to
      understand the mechanisms that mediate the effects of metoprine on water balance.

PMID- 9512084
TI  - Blocking filter vents increases carbon monoxide levels from ultralight, but not
      light cigarettes.
AB  - Effect of vent blocking on carbon monoxide (CO) exposure from a best-selling
      light cigarette was examined in 12 daily cigarette smokers. Mean CO boosts were
      not different from each other with (a) 0% filter vents blocked (5.0 ppm), (b)
      vents covered with lips (4.9 ppm), (c) 50% of vents covered with tape (4.8 ppm),
      and (d) vents covered with a pinch of the fingertips (4.9 ppm). A second study in
      another 12 smokers was conducted to replicate these findings as well as earlier
      findings that blocking vents doubles CO intake from 1-mg tar cigarettes. While
      blocking half the vents with fingers significantly increased CO boost from
      ultralight cigarettes (2.8 vs. 5.4 ppm, p < 0.001), it did not influence boosts
      from light cigarettes (6.3 vs. 6.5 ppm, p = 0.8). The lowest yield cigarettes (1
      mg tar) may be special. Smoking machine simulations provide poor models of human
      smoke intake. It is unclear whether tar and nicotine intake from light cigarettes
      was influenced by vent blocking.

PMID- 9512083
TI  - The respiratory effects of the cytokine regulating agent HP 228 alone and in
      combination with morphine in human volunteers.
AB  - HP 228 is a synthetic heptapeptide analog of alpha-MSH that attenuates the
      production and release of inflammatory cytokines. The purpose of this study was
      to define HP 228's effects, alone and in combination with morphine, on resting
      ventilation and the ventilatory response to hypoxia and hypercarbia. Six healthy
      nonsmoking young adult males completed the four-session experiment. Subjects
      first underwent an initial training session. During subsequent sessions, each
      subject was tested for the respiratory effects of intravenous HP 228 (30
      microg/kg), morphine (0.15 mg/kg), or HP 228 (30 microg/kg) plus morphine (0.15
      mg/kg) in a double-blind placebo-controlled randomized balanced within-subjects
      experimental design. Sessions began with baseline measurement of resting
      ventilation, oxygen consumption, the isocapnic hypoxic ventilatory response
      (HVR), and normoxic hypercapnic ventilatory response (HCVR). A second set of
      respiratory measurements were obtained 10 min after completion of HP 228 or
      placebo infusion. Morphine or placebo was then administered and ventilatory
      responses were determined 15 and 40 min postinfusion. HP 228 produced cutaneous
      flushing, but had no significant effect on respiration or hemodynamics. Morphine
      significantly decreased metabolism, resting ventilation, and hypoxic and
      hypercarbic ventilatory responsiveness, independent of prior HP 228
      administration. A seventh subject experienced a significant cardiac arrhythmia
      upon exposure to hypoxia after receiving both HP 228 and morphine and was
      withdrawn from further study. In conclusion, in this early Phase I clinical
      trial, HP 228 was found to neither depress ventilation nor augment morphine
      induced respiratory depression in healthy young males.

PMID- 9512085
TI  - Protective effects of moderate hypothermia on behavioral deficits but not
      necrotic cavitation following cortical impact injury in the rat.
AB  - A number of experimental studies have reported that moderate hypothermia can
      produce significant protection against behavioral deficits and/or
      morphopathological alterations following traumatic brain injury; a Phase 3
      clinical trial is currently examining the therapeutic potential for moderate
      hypothermia (32 degrees C) to improve outcome following severe traumatic brain
      injury in humans. The current study examined whether hypothermia (32 degrees C)
      provided behavioral protection following experimental cortical impact injury. The
      extent of focal cortical contusion was also examined in the same rats. A total of
      30 male Sprague-Dawley rats were trained on beam balance and beam walking tasks
      prior to injury. Under isoflurane anesthesia, cortical impact was produced on the
      right parietal cortex of 20 rats. Ten rats underwent all surgical procedures but
      were not impacted (sham-injured rats). Ten of the injured rats were cooled to 32
      degrees C (measured in temporalis muscle) beginning 5 min postinjury, maintained
      for 2 h and rewarmed slowly for 1 h. In the other 10 injured rats, normothermic
      temperatures (37.5 degrees C) were maintained for the same duration. Beam balance
      and beam walking performance was assessed daily for 5 days following injury. At
      11 days postinjury, rats were assessed for 5 days on acquisition of the Morris
      water maze task. Following behavioral assessments, rats were perfused and the
      brain removed. Coronal sections were cut through the site of cortical impact
      injury and stained with hematoxylin and eosin. Hypothermic treatment resulted in
      significantly less beam balance and beam walking deficits than observed in
      normothermic rats. Hypothermia also significantly attenuated spatial memory
      performance deficits. Quantitative morphometric analyses failed to detect any
      significant differences in volumes of necrotic tissue cavitation in cortices of
      hypothermic and normothermic rats. Hypothermic treatment also had no effect on
      volumes of dorsal hippocampal tissue or numbers of cells in CA1 or CA3 regions of
      the hippocampus. These data suggest that hypothermia, consistent with the reports
      of others, can produce significant behavioral protection following cortical
      impact injury that is not necessarily correlated with changes in focal cortical
      necrosis within the first 15 days following injury.

PMID- 9512086
TI  - Acute ethanol administration reduces the cognitive deficits associated with
      traumatic brain injury in rats.
AB  - The present study was designed to determine whether a low dose of acute ethanol
      administration could attenuate cognitive deficits associated with traumatic brain
      injury. Adult male rats received oral administration of ethanol or drinking water
      2 h prior to surgery to produce a blood ethanol concentration of 100 mg% and then
      received bilateral contusion injuries of the medial prefrontal cortex. Seven days
      after surgery, the rats began 10 days of testing for acquisition of spatial
      localization in the Morris water maze where they were required to find a hidden
      platform to escape from the water. The results indicate that the rats given
      ethanol at the time of injury later spent significantly less time searching for
      the hidden platform than their water-treated counterparts. On a memory probe test
      given on the final day of testing, in which the platform was removed from the
      pool, rats given the ethanol spent more time in the area where the platform had
      been located indicating that they learned its location better than the
      lesion/water controls. In addition, acute ethanol treatment reduced some of the
      histopathology that typically occurs following severe contusion of the medial
      frontal cortex but did not attenuate post-traumatic formation of edema. These
      results indicate that acute ethanol intoxication can reduce the severity of
      cognitive impairments caused by contusive traumatic brain injury and support the
      contention that there is a dose-response relationship of acute ethanol
      intoxication in the setting of traumatic brain injury.

PMID- 9512087
TI  - Effects of niravoline (RU 51599), a selective kappa-opioid receptor agonist on
      intracranial pressure in gradually expanding extradural mass lesion.
AB  - It has recently been reported that kappa-opioid receptor agonists inhibit
      antidiuretic hormone secretion and promote water excretion in humans and animals.
      We investigated the effect of niravoline (RU 51599), a selective kappa-opioid
      receptor agonist in the treatment of intracranial hypertension. Acute
      intracranial hypertension was induced in cats by continuous inflation of an
      extradural balloon with physiological saline at the constant rate of 0.5 ml/h for
      3 h. At this point, inflation was discontinued and the balloon remained expanded
      for an additional hour after which it was deflated. In the post-deflation period,
      monitoring continued for 1 h. The control group (n = 8) received ringer's lactate
      solution only, while the treatment group (n = 8) received an intravenous (IV)
      injection of 1.0 mg/kg of niravoline, every hour at the beginning of balloon
      inflation, during balloon inflation, in post-inflation, and at deflation time (5
      doses). Changes in intracranial pressure (ICP), mean arterial blood pressure
      (MAP), cerebral perfusion pressure (CPP), electroencephalogram (EEG), blood
      gases, pupil size, serum electrolytes, and osmolality were measured in both
      groups. Brain water content was determined in a separate group of cats at the end
      of a 3-h extradural brain compression. Compared to the untreated group, the
      niravoline-treated group had a significantly lower ICP and higher CPP at the 2
      and 3 h during balloon inflation, in post-inflation, and in post-deflation
      periods. Brain water content was significantly reduced in niravoline-treated
      animals. No significant change was observed in serum osmolality throughout the
      experiment. Our results indicate that the mechanism by which niravoline reduces
      ICP is partly via a reduction in brain water content. Also, the current findings
      suggest that in clinical situations in which ICP is elevated due to the pressure
      of an extradural mass, niravoline may effectively reduce ICP while maintaining
      adequate CPP until the mass is removed.

PMID- 9512088
TI  - A mouse model of graded contusive spinal cord injury.
AB  - A mouse model of spinal cord injury (SCI) could further increase our basic
      understanding of the mechanisms involved in injury and recovery by taking
      advantage of naturally-occurring and genetically engineered mutations available
      in mice. We have, therefore, investigated whether methods used to produce and
      evaluate graded experimental contusive SCI in the rat could be modified to
      produce a mouse model of traumatic SCI. C57BL6 mice were anesthetized with 2,2,2
      tribromoethanol and a restricted laminectomy performed at the T8 vertebral level.
      The spinal column was stabilized and a weight drop technique used to produce
      contusive injury. Experimental groups were distinguished by the amount of weight
      or the height from which the weight was dropped onto an impounder resting on the
      dura (1 g x 2.5 cm, 2 g x 2.5 cm, 3 g x 2.5 cm, and 3 g x 5.0 cm). Functional
      deficits over time were examined up to 28 days after SCI by testing hindlimb
      reflex responses and coordinated motor function. Chronic lesion histopathology
      was evaluated by light microscopy and analyzed with morphometric techniques. All
      groups demonstrated profound functional deficits after injury followed by gradual
      recovery. Recovery correlated with the weight dropped and percent of white matter
      spared that was 41.3+/-6.0% (mean +/- SEM) in the 2 g x 2.5 cm group and 24.3+/
      5.0% in the 3 g x 2.5 cm group. A replicate experiment confirmed reproducibility
      of the injury. This new mouse model of contusive SCI could pave the way for in
      vivo studies of the effect of genetic modifications produced by specific
      mutations on injury and recovery processes after spinal cord trauma.

PMID- 9512089
TI  - Indirect glutamate neurotoxicity.
AB  - Indirect glutamate toxicity can be demonstrated by exposing dissociated rat
      hippocampal cultures to the media of the same culture transiently exposed (1 min)
      to glutamate (0.5 mM). The toxicity was maximum when the media was collected 5
      min after the glutamate exposure. While the primary glutamate toxicity was
      attenuated by ionotropic glutamate receptor antagonists, the transferred,
      indirect toxicity was unaffected by the same antagonists. The changes in nuclear
      morphology indicated chromatin condensation and nuclear fragmentation in both
      primary and transferred toxicity. The stain for DNA damage by TUNEL method also
      revealed cells staining positive in both primary and transferred glutamate
      toxicity. These observations demonstrate that glutamate-induced neurotoxicity can
      be propagated to the uninjured cells by an unknown toxin released into the
      extracellular space. This neurotoxin induced both apoptosis and necrosis in
      cultured rat hippocampal cells.

PMID- 9512090
TI  - Voluntary muscle weakness and co-activation after chronic cervical spinal cord
      injury.
AB  - Muscle strength was assessed from the maximum force that could be exerted
      voluntarily by triceps brachii muscles of 72 people with chronic cervical spinal
      cord injury (SCI) at or above C7, and 18 able-bodied (A-B) subjects. The
      magnitude of co-activation was estimated from the ratio of biceps brachii surface
      EMG to triceps plus biceps brachii surface EMG (biceps EMG/ triceps + biceps
      EMG). Maximum voluntary forces exerted by triceps brachii muscles of SCI subjects
      were significantly lower than those of controls (p < 0.01). Strength differences
      between muscles of SCI men and women were not evident. Significant positive
      relationships were found (linear or curvilinear) between triceps surface EMG and
      force for all control muscles (n = 19) and for 54% of the muscles of SCI subjects
      (n = 73). The remaining muscle of SCI subjects (n = 63) were either so weak that
      only one EMG and force value could be measured or EMG occurred without detectable
      force. For control muscles (n = 19), the mean triceps-biceps EMG ratio was 0.15+/
      0.05 for all voluntary contraction force levels. For muscles of SCI subjects, 41
      had EMG ratios similar to those of controls, co-activity largely attributed to
      EMG cross talk; 19 muscles had constant EMG ratios, but these were three standard
      deviations above the control means; 13 muscles had EMG ratios that decreased or
      increased as force increased. Muscles of SCI subjects with greater than control
      levels of co-activity during maximum voluntary contractions (high EMG ratios)
      were as strong as muscles with EMG ratios similar to controls. These results
      provide quantitative descriptions of voluntary muscle weakness after SCI and a
      database from which to evaluate improvements in muscle strength. These data also
      show that, for many SCI subjects, any triceps-biceps co-activation is similar to
      that of controls and does not necessarily distort muscle control unduly.

PMID- 9512092
TI  - Ex vivo effects associated with the expression of a bcr-abl-specific ribozyme in
      a CML cell line.
AB  - The bcr-abl chimeric gene is found in 95% of chronic myeloid leukemia (CML)
      patients and is thought to be seminal to the etiology of the disease. The
      possibility of using ribozymes to suppress bcr-abl gene expression and
      subsequently alter the malignant phenotype of hematopoietic cells may provide an
      alternative therapeutic approach to current regimens. A series of hammerhead
      ribozymes targeted to a b3a2 bcr-abl transcript has been developed and previously
      shown to be capable of cleaving the desired sequence with varying degrees of
      specificity. This study investigated the ex vivo effects of endogenous expression
      of these ribozymes in a CML cell line, K562. We demonstrated a 53% decrease in
      bcr-abl mRNA levels in a clone induced to express Rz8, compared with its
      uninduced control. Phenotypic analysis of this clone also revealed a 63% decrease
      in colony-forming ability and a 43% inhibition of cell proliferation following
      ribozyme expression. Morphologic analysis of cells showed there was a slight
      increase (2.5% to 15%) in the number of cells undergoing apoptosis. These results
      suggest that Rz8 was effective in suppressing bcr-abl gene expression within a
      cellular environment and altering the leukemic nature of a CML cell line.

PMID- 9512091
TI  - Structural similarities between hammerhead ribozymes and the spliceosomal RNAs
      could be responsible for lack of ribozyme cleavage in yeast.
AB  - Hammerhead ribozymes have been proposed as potential therapeutic agents for the
      treatment of viral and other diseases. However, a clear understanding of the
      cleavage reaction in vivo is not available at present. In these studies, we chose
      the yeast Saccharomyces cerevisiae as a model system to study the effects of
      hammerhead cleavage on gene expression in vivo. Several reporter genes were
      employed to monitor the self-cleaving characteristics of three different
      ribozymes. We show that these ribozymes decrease expression of some reporter
      genes by interfering with splice site selection or translation initiation and not
      by in vivo cleavage of the RNA transcripts. In fact, it appears that although
      these ribozymes can efficiently self-cleave the RNA in vitro, they are not able
      to function in vivo. We have identified a yeast splicing protein that interacts
      in vivo with our cis-ribozyme by specifically recognizing the ribozyme structure
      (Lin and Rossi, 1996). This interaction does not occur if different secondary
      structures are used in place of the ribozyme. The binding of this protein to the
      ribozyme can account for the inability of ribozymes to efficiently cleave in
      yeast. Remarkably, when yeast extracts are added to in vitro trans-cleavage
      reactions, the cleavage ability of the ribozyme is hampered, whereas the addition
      of mammalian extracts yields an enhancement of the reactions. These results
      confirm the presence of factor(s) that can block ribozyme function in the yeast
      intracellular environment.

PMID- 9512093
TI  - Antisense oligonucleotides and myotonin gene expression in C2 mouse cells.
AB  - By describing the behavior of myotonin mRNA levels, from the quiescent to the
      differentiated state in C2 mouse myoblasts, we produced evidence bearing on the
      role of myotonin gene product in the control of cell growth and differentiation.
      To study the role of myotonin in myotonic dystrophy (DM) pathogenesis, we
      developed a suitable cellular model where myotonin gene expression was modulated
      by phosphorothioate antisense oligonucleotides in C2 cultured cells. Furthermore,
      an isoform of the gene product, similar to that described in humans and not yet
      described in the mouse, was found.

PMID- 9512094
TI  - Impact of 3'-exonuclease stereoselectivity on the kinetics of phosphorothioate
      oligonucleotide metabolism.
AB  - For the enzymatic digestion of a 25-mer phosphorothioate (PS) oligonucleotide,
      the reaction kinetics was previously determined to be the sum of two parallel
      processes: a fast and a very slow phase of digestion suggesting a two-exponential
      model. A characteristic metabolite profile was observed both in vitro and in
      vivo. This behavior is shown to be the result of the stereoselective cleavage of
      chiral R-configuration and S-configuration PS internucleotide linkages by 3'
      exonucleases. The stereoselective nature of 3'-exonuclease action was analyzed by
      reverse-phase HPLC. The separation of eight diastereomers of the tetramer TTCT
      (5'-3') was used to follow the stereoselective course of exonuclease hydrolysis
      of PS internucleotide linkages. Degradation of the 25-mer parent compound having
      a 3' S-terminal internucleotide linkage was calculated to be more than 300 times
      slower than an analog with a 3'-terminal R-configuration. These results support
      an approach for protecting antisense oligonucleotides based on the chirality of
      only the 3'-end internucleotide linkage.

PMID- 9512095
TI  - Pharmacokinetics and metabolism of an oligodeoxynucleotide phosphorothioate
      (GEM91) in cynomolgus monkeys following intravenous infusion.
AB  - The pharmacokinetics and metabolism of an antisense oligonucleotide
      phosphorothioate (GEM91) were studied in cynomolgus monkeys following intravenous
      infusion. [35S]-Labeled GEM91 was administered to 12 monkeys by means of a 2-hour
      intravenous infusion at a dose of 4 mg/kg. Plasma pharmacokinetic analysis
      revealed that the maximum plasma concentration was 41.7 microg equivalents/ml,
      which was achieved in 2.13 hours. The plasma elimination half-life was 55.8 hours
      based on radioactivity levels. Urinary excretion represented the major pathway of
      elimination, with 70% of the administered dose excreted in urine over 240 hours.
      The oligonucleotide was widely distributed to tissues. The highest concentrations
      were observed in the liver and kidney. Analysis of the extracted oligonucleotide
      following post-labeling with [32p] on polyacrylamide gel electrophoresis showed
      the presence of both intact and degraded oligonucleotide in plasma, kidney,
      liver, spleen, and lymph nodes. Based on the methods used for post-labeling
      (either 3'-end or 5'-end), different patterns of bands were observed on
      polyacrylamide gel electrophoresis, suggesting metabolic modification of the
      administered oligonucleotide.

PMID- 9512096
TI  - Molecular cloning and expression of cDNA for human RNase H.
AB  - We have cloned, expressed, and purified to electrophoretic homogeneity a human
      RNase H. The enzyme has a molecular weight of 32 kDa, is Mg2+ dependent, and is
      inhibited by Mn2+ and N-ethylmaleimide. Its molecular weight and cleavage
      characteristics are consistent with type 2 human RNase H. The human RNase H we
      have cloned is highly homologous to Escherichia coli RNase HI (33.6% amino acid
      identity) and to other RNase H enzymes homologous to E. coli RNase HI. The enzyme
      is encoded by a single gene that is at least 10 kb in length and is expressed
      ubiquitously in human cells and tissues.

PMID- 9512097
TI  - Improving the efficiency of antisense and EGS methods.
AB  - Hammerhead ribozymes and stable stem loop structures function as inhibitors of 3'
      5'-exonuclease degradation of external guide sequences (EGSs) when covalently
      linked to the 3'-end of EGS RNAs. This observation may be of use in improving the
      efficiency of gene inactivation techniques that use single-stranded RNA (e.g.,
      antisense RNA, EGS RNA) in vivo.

PMID- 9512098
TI  - Cellular uptake properties of oligonucleotides in LLC-PK1 renal epithelial cells.
AB  - The objective of this study was to clarify the renal uptake characteristics of
      oligonucleotides at a cellular level using LLC-PK1 renal epithelial cells derived
      from the proximal tubule. The association of [35S]-labeled 20-mer phosphodiester
      (PO) and phosphorothioate (PS) oligonucleotides with the monolayers of polarized
      LLC-PK1 cells cultured on polycarbonate filter was characterized after apical or
      basolateral application. The cellular association of PO and PS at both apical and
      basolateral membranes was time dependent and temperature dependent, and the
      apparent association amount of PS was larger than that of PO. The PO and PS
      association after apical application was saturable, with the apparent Km and Vmax
      values determined to be 5.4 microM and 0.14 nmol/mg protein for PO and 0.22
      microM and 0.11 nmol/mg protein for PS, respectively. In contrast, almost linear
      kinetics were observed after basolateral application within a tested
      concentration range. The association was inhibited significantly by sodium azide
      and chloroquine, suggesting that an energy-dependent endocytotic process was
      involved. Internalization and subsequent transport to endosome and lysosome
      compartments of FITC-labeled oligonucleotides were shown by confocal laser
      scanning microscopy. The present study has demonstrated that both types of
      oligonucleotides are taken up by LLC-PK1 cells from both apical and basolateral
      surfaces probably via an endocytosis mechanism.

PMID- 9512099
TI  - Scleroderma and cutaneous sclerosis. Introduction.

PMID- 9512100
TI  - The pathogenesis of cutaneous fibrosis.
AB  - Cutaneous fibrosis is an integral component of a variety of human disorders
      including keloids, hypertrophic scar, and most notably, scleroderma. Each has its
      own etiology and unique clinical characteristics, but all involve the
      dysregulation of connective tissue metabolism, in particular, the activation of
      dermal fibroblasts. In this review, we examine various molecular events in
      scleroderma that may lead to fibroblast activation, and propose a new model to
      explain the persistence of such activation by scleroderma fibroblasts in the
      apparent absence of exogenous stimuli.

PMID- 9512101
TI  - Vascular abnormalities in scleroderma.
AB  - Vascular abnormalities represent a fundamental event in the pathogenesis of
      systemic sclerosis. This review focuses on key observations that support this
      view and builds a framework with which to clarify our understanding of how
      endothelial cell damage may trigger a self-fueling process ending in pathological
      tissue fibrosis in those susceptible to scleroderma. The studies reviewed in this
      article pertain to systemic sclerosis patients.

PMID- 9512102
TI  - Immunologic abnormalities in scleroderma.
AB  - The immune system abnormalities of scleroderma are diverse and in association
      with vascular and mesenchymal cell abnormalities, contribute to the organ system
      dysfunction and clinical expression of the disease. Recent insights into novel
      immune regulatory pathways, immune reactivity to self-antigens, and the potential
      association of persistent fetal cells and disease expression may serve to
      increase our understanding of this enigmatic disease.

PMID- 9512103
TI  - Classification and epidemiology of scleroderma.
AB  - Scleroderma is classified as two separate but related entities, a localized form
      and a systemic form. The classification scheme for morphea presented here is that
      of Peterson et al, which divides morphea into five categories: plaque,
      generalized, bullous, linear, and deep. Using this system, these authors
      estimated the incidence rate of localized scleroderma to be 27 new cases per
      million population per year. Overall survival was similar to that of the general
      population. There was a preponderance of female cases (approximately 3:1) for all
      forms of morphea except for linear scleroderma, which had an even sex
      distribution. Systemic scleroderma is divided into limited and diffuse disease
      based on the extent of skin involvement. Recent estimates have placed the
      incidence rate of systemic sclerosis in the United States at 19 new cases per
      million adults per year, with an overall prevalence of 240/million adults. The
      female-to-male ratio is approximately 5:1. The prevalence of scleroderma varies
      by geographic region and ethnic background and is higher in the United States
      than in Europe or Japan. Although systemic sclerosis survival has improved over
      the past two decades, with 5-year survival over 80%, long-term survival is
      significantly lower than expected, and morbidity is considerable.

PMID- 9512104
TI  - Localized scleroderma.
AB  - Localized scleroderma can be divided into three main subtypes: morphea, linear
      scleroderma, and generalized morphea. Plaque morphea usually has a good
      prognosis. Variants of morphea, including guttate morphea and atrophoderma of
      Pasini and Pierini, are seen. Linear scleroderma, whether involving an extremity
      or the face, is often associated with serological abnormalities. Cosmetic and
      functional prognosis may be poor. Therapy is usually ineffective. Generalized
      morphea may be difficult to differentiate from systemic scleroderma. However,
      progression to systemic scleroderma is uncommon.

PMID- 9512105
TI  - Management of localized scleroderma.
AB  - Localized scleroderma denotes a spectrum of conditions characterized by
      circumscribed fibrotic areas involving different levels of the dermis, subcutis,
      and sometimes underlying soft tissue and bone. Although the clinical course of
      the disease is often benign, widespread lesions and disabling joint contractures
      may lead to significant complications. The pathogenesis of the different types of
      localized scleroderma is still unknown. Numerous therapeutic agents have been
      reported to be effective in this disease spectrum, but controlled studies are
      rare. The purpose of this review is to summarize previous experience and to
      discuss recent advances in the management of localized scleroderma.

PMID- 9512106
TI  - Pediatric scleroderma.
AB  - Scleroderma is a diverse group of conditions which have in common fibrosis of
      skin and other tissues. Although less common in children than in adults, these
      conditions are an important cause of morbidity and occasional mortality when they
      occur in the pediatric population. Children are more likely than adults to
      develop localized forms of scleroderma, and because of the impact on growth,
      these can result in major facial or limb asymmetry, flexion contractures, and
      disability. Management approaches must take into consideration the effect of
      medications on the child (for example, growth failure and osteoporosis from
      corticosteroids) as well as the psychosocial impact of chronic illness and
      physical deformity on the child and family. This article describes the types of
      scleroderma identified in children, reviews epidemiologic and etiologic factors,
      and discusses management options. Because this is a rare group of diseases
      managed by both dermatologists and rheumatologists, large series of patients are
      rare, and controlled studies of management are not available.

PMID- 9512107
TI  - Clinical manifestations of systemic sclerosis.
AB  - Systemic sclerosis is a multisystem disease characterized by inflammation and
      fibrosis of many organs. There are two major subsets, limited cutaneous (the old
      CREST syndrome) and diffuse cutaneous scleroderma. The major difference is the
      pace of disease. Limited scleroderma patients often have a long history of
      Raynaud's phenomenon before other symptoms. They have skin thickening limited to
      hands and frequently have problems with digital ulcers and esophageal
      dysmotility. Although generally a milder form than diffuse scleroderma, they can
      have life-threatening complications from small intestine hypomotility and
      pulmonary hypertension. Diffuse scleroderma patients have a much more acute
      onset, with many constitutional symptoms, arthritis, carpal tunnel syndrome, and
      marked swelling of hands and legs. They get widespread skin thickening,
      progressing from their fingers to their trunk. Internal organ problems, including
      gastrointestinal and pulmonary fibrosis, are common, but severe life-threatening
      involvement of the heart and kidneys occurs. Understanding the type of disease
      that occurs in these two subsets will enable the physician to anticipate
      problems, aggressively treat those that can be treated, and give the patient a
      better understanding of their disease.

PMID- 9512108
TI  - Management of systemic sclerosis: the art and science.
AB  - There have been substantial strides in the therapy of systemic sclerosis (SSc) in
      recent years, particularly in the management of individual organ manifestations.
      Effective treatments are available for SSc renal crisis and many of the
      gastrointestinal manifestations of the disease. Raynaud's phenomenon, a nearly
      universal problem in SSc, also may be effectively managed. Treatment of the
      pulmonary complications, pulmonary hypertension and interstitial lung disease,
      remains difficult. Patients with early, diffuse SSc are the best candidates for
      experimental therapies intended to modify the overall disease process. Most
      disease-modifying agents have been directed at the fibrotic and inflammatory
      processes characteristic of SSc and have achieved little success. Future
      therapies may target mediators of vascular dysfunction in SSc. The success of
      future therapeutic trials will depend on collaborative efforts between treatment
      centers.

PMID- 9512109
TI  - Scleroderma-like disorders.
AB  - Scleroderma-like disorders are widely disparate conditions mimicking either
      systemic sclerosis or cutaneous localized scleroderma, not infrequently
      displaying features of both. Some are exclusively sclerotic, some scleroatrophic
      with prevailing sclerosis or atrophies. The recognition of scleroderma-like
      disorders is of practical importance because by establishing the cause of the
      disease, it is possible to introduce an effective therapy, as in scleredema
      Buschke or scleredema diabeticorum, sclerodermiform porphyria, Borrelia
      burgdorferi-induced sclerodermiform acrodermatitis atrophicans, sclerodermiform
      phenylketonuria, drug-induced conditions, and so on. Scleroderma-like disorders
      strongly suggest that the pathogenesis of skin sclerosis and internal involvement
      may be divergent, and of various causes. Some of them, such as atrophoderma
      Pasini-Pierini or progressive facial hemiatrophy, frequently overlapping with
      scleroderma, make the differentiation very difficult, if at all possible, and the
      diagnosis is often arbitrary. Some, as sclerodermiform graft-versus-host
      reaction, point to the autoimmune origin of scleroderma. The amply-covered
      congenital sclerodermiform conditions present a large spectrum of still not
      widely known and extremely heterogeneous syndromes, associated with numerous
      anomalies and/or malignancies.

PMID- 9512110
TI  - Increased LFA-1 expression in intestines of rats with GVHD after small bowel
      transplantation.
AB  - Experimental graft-versus-host disease (GVHD) causes immune-mediated intestinal
      injury. The adhesion molecule lymphocyte function associated antigen-1 (LFA-1) is
      involved in leukocyte homing to areas of inflammatory injury. Our hypothesis was
      that LFA-1 is increased in the GVHD injured small bowel and colon. We found that
      animals with GVHD caused by auxiliary small bowel transplantation displayed
      significantly increased expression of intestinal LFA-1alpha at times of clinical
      illness when compared to controls. The staining pattern progressed from a few
      discretely stained cells in the lamina propria on day 5 to diffuse confluent
      staining of lamina propria on day 13 and was statistically significantly
      increased from controls at days 10 and 13. CyA-treated animals had intermediate
      staining between control and day 13 GVHD animals. There was no difference between
      sham-operated control animals and SBTx animals with GVHD in the amount of
      staining for LFA-1 in extraintestinal organs normally affected by GVHD. We
      conclude that: (1) LFA-1 expression in the small bowel and colon progressively
      increased during GVHD after SBTx; and (2) CyA treatment is associated with
      decreased LFA-1 expression in the small bowel and colon of GVHD animals after
      SBTx. LFA-1 may play an important role in immune-mediated injury of the
      intestine.

PMID- 9512111
TI  - Venoocclusive disease of the liver following renal transplantation.

PMID- 9512112
TI  - Augmented eradication rates of Helicobacter pylori by new combination therapy
      with lansoprazole, amoxicillin, and rebamipide.
AB  - The aim of the present study was to determine the efficacy of a new combination
      regimen including an antioxidant, a proton pump inhibitor, and antibiotics
      against Helicobacter pylori and to document the changes of oxidative stress and
      cytokines involved in H. pylori-associated gastric inflammation. From 57 patients
      with endoscopically diagnosed gastric and/or duodenal ulcers associated with H.
      pylori infection five gastric antral biopsy specimens were taken for the
      diagnosis of H. pylori and for the experimental measures. The patients were then
      treated either with lansoprazole 30 mg + amoxicillin 1.5 g (LA group; 21
      patients) or lansoprazole 30 mg + amoxicillin 1.5 g + rebamipide 300 mg (LAM
      group; 36 patients) for two weeks. Four weeks after the initiation of treatment,
      the patients were endoscoped again and biopsy specimens were obtained. Mucosal
      malondialdehyde (MDA) levels; myeloperoxidase (MPO) activities; superoxide
      dismutase; catalase; glutathione peroxidase; cytokines IL-1, IL-6, TNF-alpha; and
      chemokines IL-8, GRO-alpha, RANTES (regulated on activation normal T expressed
      and secreted) were measured. Using paraffin-embedded tissue sections, in situ
      terminal deoxyribonucleotide transferase (TdT) mediated dUTP nick end labeling
      (TUNEL) for apoptosis and immunohistochemical staining for inducible nitric oxide
      synthase (iNOS) were performed. Two weeks of treatment with the LA regimen
      resulted in 57.4% eradication rates of H. pylori, whereas two weeks of treatment
      with the LAM regimen resulted in 75.0% eradication rates. Eradication rates
      between these two groups were statistically significantly different (P < 0.05).
      Mucosal MDA levels and MPO activities were significantly lower in the LAM group
      than the LA group. Mucosal levels of cytokines IL-1, IL-6, and TNF-alpha and of
      chemokines IL-8, GRO-alpha, and RANTES were all significantly decreased after the
      treatment of H. pylori, especially so in the LAM group. The apoptotic index and
      iNOS score were significantly reduced after the eradication of H. pylori. The
      addition of an antioxidative drug to the eradication regimen against H. pylori
      has advantages either in augmenting the eradication rates of H. pylori or in
      decreasing the oxidative stress and cytokines levels generated by H. pylori
      infection.

PMID- 9512113
TI  - Responses to different levels of esophageal acidification during waking and
      sleep.
AB  - The purpose of this study was to assess the effect of hydrogen ion concentration
      of intraesophageal infusions during sleep on acid clearance time and latency to
      swallow and arousal responses from sleep. We studied 10 normal volunteers during
      sleep via polysomnography and concomitant esophageal pH monitoring. Sleep
      prolonged the acid clearance time of both pH 3.0 and 1.2. Swallow and arousal
      latencies were both progressively decreased with decreasing pH of the infusate (P
      < 0.05, 0.07, respectively). We concluded that intraluminal hydrogen ion
      concentration creates an afferent warning stimulus that produces prompt airway
      protective responses.

PMID- 9512114
TI  - HLA class I and II profiles of patients presenting with Chagas' disease.
AB  - To evaluate the HLA class I and II profiles of a large group of patients with
      Chagas' disease, 176 patients presenting with pure cardiomyopathy with heart
      failure (N = 60), cardiomyopathy without heart failure (N = 18), pure digestive
      tract manifestations (N = 25), cardiac plus digestive disease (N = 40), and
      asymptomatic patients with positive serology for chronic Trypanosoma cruzi
      infection (N = 33) were studied. A total of 448 normal individuals were also
      studied in parallel. HLA class I and II specificities were determined using
      serology and oligonucleotide analysis. HLA-A30 antigen was overrepresented in the
      total group and in the subgroups presenting with the pure cardiac (with or
      without heart failure) or digestive form, conferring similar relative risks and
      etiologic fractions on all these presentation forms. Serologic HLA class II
      analysis showed that HLA-DQ1 conferred susceptibility to, while HLA-DQ7 antigen
      conferred protection against the development of the disease in the total group of
      patients. Oligonucleotide typing did not confirm the HLA class II associations
      obtained by serology, but showed that HLA-DQB1*06 alleles were underrepresented
      in the total group and in the subgroups presenting with pure digestive or cardiac
      disease, conferring closely similar relative risks and preventive fractions.
      Although asymptomatic patients showed a tendency to increased HLA-A30, they
      presented a significant increase of HLA-DQB1*0302 specificity. In conclusion, HLA
      A30 antigen conferred susceptibility to, while HLA-DQB1*06 specificity conferred
      protection against, the development of the disease, regardless of the form of
      presentation, ie, cardiac or digestive tract disease.

PMID- 9512115
TI  - Human gastric carcinoid detected during long-term antiulcer therapy of H2
      receptor antagonist and proton pump inhibitor.

PMID- 9512116
TI  - Influence of H. pylori infection on gastric motor and sensory function in
      asymptomatic volunteers.
AB  - The effect of H. pylori infection on gastric motility and sensation is unclear.
      Our hypothesis is that H. pylori infection increases gastric sensation and
      reduces gastric accommodation and emptying. In eight H. pylori-positive and eight
      H. pylori-negative asymptomatic subjects, infection was proven by antral
      histology or culture. We evaluated: (1) gastric emptying of solids, (2) proximal
      gastric compliance, (3) fasting and postprandial proximal gastric tone and phasic
      contractions, (4) gastric sensation during balloon inflations or ingestion of
      cold water, and (5) abdominal vagal function. H. pylori infection was associated
      with lower gastric accommodation (median 75% postprandial increase in barostat
      balloon volume compared to fasting) when compared to the accommodation in
      uninfected volunteers (median 211% change from fasting). One H. pylori-positive
      subject had an abnormal abdominal vagal function test and her gastric
      accommodation response was reduced. Other motor and sensory functions in the two
      groups were similar. In asymptomatic volunteers, H. pylori infection and
      gastritis result in reduced accommodation (diastolic dysfunction) but no change
      in overall sensation or motor functions of the stomach.

PMID- 9512117
TI  - Human small bowel motor activity in response to liquid meals of different caloric
      value and different chemical composition.
AB  - Previous animal studies have shown that the nature and duration of postprandial
      motility in the small bowel depend both on the caloric load and the chemical
      composition of a meal. It is not clear whether this is also true for the human
      small bowel. Therefore we investigated the motor activity of the human small
      bowel in response to nutrient liquids of different caloric value and different
      chemical composition. Ten human volunteers underwent three separate, 24-hr
      ambulatory manometry studies. They drank water, a pure glucose solution, and
      Intralipid 10% in volumes of both 300 and 600 ml. The caloric value of the
      nutrient liquids was 330 and 660 kcal, respectively. Records were analyzed
      visually for the reappearance of phase III of the MMC after ingestion of a test
      liquid, and a validated computer program calculated the incidence and amplitude
      of contractions during the postprandial period. Neither duration of the
      postprandial interval nor the mean incidence or mean amplitude of contractions
      were different between the fat and the carbohydrate solutions, but phase III
      reappeared significantly later after ingestion of the nutrient liquids than after
      water (P = 0.0002). Duration of the postprandial interval also depended on the
      volume or the caloric load of a liquid meal (P = 0.0012). Mean incidence of
      contractions tended to be higher after ingestion of nutrient liquids than after
      water (P = 0.059). We conclude that in ambulant subjects, small bowel motor
      activity in response to chemically diverse liquid meals is remarkably uniform.
      This is true for the duration of the postprandial motor activity, as well as the
      incidence and amplitude of contractions during that period. The caloric value of
      a liquid meal, however, regulates the duration of the postprandial interval in
      the human small bowel.

PMID- 9512118
TI  - Myenteric plexus neurons in culture: developmental changes in neurofilament and
      related proteins.
AB  - Myenteric plexus neurons appear to have unique features in their expression of
      cytoskeletal proteins. In particular, neurofilaments have been shown to be
      present in a subset of neurons, and the medium molecular weight subunit of
      neurofilament is modified during the first week of development. We utilized
      cultured myenteric plexus neurons to examine if these changes could be reproduced
      outside of the intestinal wall. Myenteric neurons from neonate rat small
      intestine were cultured using a dissection and enzymatic dispersion technique
      previously described, and cells were fixed after one day or seven days in
      culture. Antibodies to the neurofilament proteins, peripherin, alpha-internexin,
      nestin, and microtubule-associated proteins tau and tubulin were studied. Similar
      to what was seen in tissues, cultured cells initially stained and then lost
      staining for antibodies to one area of the carboxy terminal region of
      neurofilament during the first week in culture. Peripherin and alpha-internexin
      showed good staining both initially and after 7 days in culture (differing from
      intact tissues). Developmental modifications in immunoreactivity to neurofilament
      proteins in myenteric neurons occur both in culture and in intact tissues.
      However, the intermediate filament proteins peripherin and alpha-internexin
      immunolocalized in cultured neuron cells differently than in intact tissues.
      Thus, factors other than the intact intestinal wall appear to be responsible for
      these unique cytoskeletal characteristics in myenteric plexus neurons.

PMID- 9512119
TI  - Expression of p53 and p21WAF1/CIP1 proteins in gastric and esophageal cancers:
      comparison with mutations of the p53 gene.
AB  - The p53 gene has been shown to be commonly mutated in various human cancers, and
      mutant p53 can act as a dominant oncogene. The intact p53 protein is also known
      to induce the cyclin-dependent kinase inhibitor p21WAF1/CIP1 and is implicated in
      cell cycle arrest. We investigated p53 gene alterations in gastric adenocarcinoma
      and esophageal squamous cell carcinoma to elucidate the association of the
      nuclear accumulation of the p53 protein and/or p21WAF1/CIP1 protein.
      Abnormalities of the tumor suppressor gene p53 protein and the expression of
      p21WAF1/CIP1 protein were analyzed by immunohistochemical techniques in 32 cases
      of gastric adenocarcinoma and 15 cases of esophageal squamous cell carcinoma.
      Twenty cases of gastric cancer and five cases of esophageal cancer were also
      analyzed for p53 gene mutation by polymerase chain reaction and direct nucleotide
      sequencing. Overexpression of p53 protein was found in 13/32 (41%) of gastric
      cancers and 5/15 (33%) of esophageal cancers. We found immunodetectable p53 in
      10/14 cases with mutations and in none of 11 cases without mutations in gastric
      and esophageal cancers. Hence, immunohistochemical and genetic analyses gave
      concordant results in 84% of 25 cases, revealing a good correlation between
      immunostaining of p53 and missense mutation of the p53 gene. p53 immunostaining
      was not observed in cases with frameshift or splicing mutation. The expression of
      p21WAF1/CIP1 protein was found in 9/32 (29%) of gastric cancers and 4/15 (27%) of
      esophageal cancers and in 2/14 (14%) cases with alteration of the p53 gene and in
      5/11 (45%) without. These results suggest that abnormalities of p53 may be
      closely associated with the pathogenesis of gastric adenocarcinoma and esophageal
      squamous cell carcinoma and that the immunoreactivity of p53 protein is a general
      indicator of the tumors with altered p53 function. The expression of p21WAF1/CIP1
      protein was suppressed in the neoplastic tissues with and without p53 gene
      alteration.

PMID- 9512120
TI  - Specificity of polymerase chain reaction monoclonality for diagnosis of gastric
      mucosa-associated lymphoid tissue (MALT) lymphoma: direct comparison to Southern
      blot gene rearrangement.
AB  - The specificity of polymerase chain reaction monoclonality in the diagnosis of
      gastric lymphoma was prospectively evaluated. Gastric mucosal tissue from normal
      gastric mucosa (N = 13), benign gastric ulcers (N = 3), chronic Helicobacter
      pylori gastritis (N = 3), gastric mucosa-associated lymphoid tissue (N = 16), and
      gastric lymphoma (N = 15) was obtained. Polymerase chain reaction amplification
      of the heavy-chain framework 2A gene was performed. The sensitivity and
      specificity of heavy-chain clonality, in the detection of gastric lymphoma, were
      73.3% and 45.7%, respectively. Determination of monoclonality by polymerase chain
      reaction methodology is not an acceptable technique for confirming the diagnosis
      of gastric lymphoma as it is too sensitive, detecting minute populations of
      clonal lymphocytes that occur in benign diseases as well as larger populations of
      clonal lymphocytes associated with malignant gastric lymphoproliferative
      diseases. Southern blot gene rearrangement testing should be utilized to
      determine clonality in the evaluation of gastric lymphocytic infiltrates.

PMID- 9512121
TI  - Rapidly growing primary gastric CD30 (Ki-1)-positive anaplastic large cell
      lymphoma.

PMID- 9512122
TI  - Screening for APC mutations based on detection of truncated APC proteins.
AB  - Mutation of the adenomatous polyposis coli (APC) gene is frequently found in
      colorectal tumors from both familial adenomatous polyposis (FAP) and non-FAP
      patients. Analysis of APC mutation is time-consuming and costly due to the large
      size of the APC gene. As the majority of APC mutations result in the truncation
      of gene products, the detection of truncated APC proteins may be used as a
      screening method for APC mutations. The aim of this study is to establish a
      practical method of detecting truncated APC proteins for the screening of APC
      mutations. APC proteins in human colorectal cancer cell lines were analyzed by
      western blotting. Truncated APC proteins were expressed in all of the colorectal
      cancer cell lines studied. Two species of truncated APC proteins were expressed
      in two cell lines. Western blotting is a rapid, reliable screening method for APC
      mutations and provides information on both alleles.

PMID- 9512123
TI  - Prostaglandin levels in human colorectal mucosa: effects of sulindac in patients
      with familial adenomatous polyposis.
AB  - Recent evidence suggests that nonsteroidal antiinflammatory drugs (NSAIDs) may
      prevent colorectal cancer. The mechanism of action of NSAIDs in chemoprevention
      is unknown but may be linked to their effect on mucosal prostaglandin levels.
      Levels of five major prostaglandin metabolites were measured by gas
      chromatography-mass spectrometry in biopsy specimens of flat rectal mucosa from
      four patients with familial adenomatous polyposis (FAP) before and after sulindac
      therapy and from five healthy individuals. The prostaglandin present at highest
      concentration in rectal mucosa from FAP and control subjects was prostaglandin
      E2. The concentration of thromboxane B2 alone was significantly elevated in FAP
      patients compared to controls (P = 0.016). In FAP patients treated with sulindac,
      all prostaglandin metabolite levels were significantly reduced compared to
      pretreatment levels (P < 0.05) except prostaglandin D2 (P = 0.07). Prostaglandins
      D2, E2, F2alpha, and 6-keto-F1alpha levels also were significantly reduced in FAP
      patients on sulindac compared to healthy controls (P < 0.05). However,
      interpatient heterogeneity of response to sulindac was evident with changes
      ranging from +19% to -89%, and the patient with the greatest reductions after
      sulindac developed colorectal cancer after 35 months of therapy. Sulindac
      treatment, at drug doses shown to regress colorectal adenomas in FAP patients,
      has heterogeneous effects on the level of major prostaglandins in their rectal
      mucosa and may not prevent colorectal cancer due to uncoupling of prostaglandin
      levels and carcinogenesis.

PMID- 9512124
TI  - Hepatic perfusion changes after transcatheter arterial embolization (TAE) of
      hepatocellular carcinoma: measurement by dynamic computed tomography (CT).
AB  - We observed the hemodynamic changes at the level of the hepatic parenchyma
      induced by transcatheter arterial embolization (TAE) for hepatocellular carcinoma
      in 22 patients. TAE was performed by administration of a mixture of iodized oil,
      adriamycin, and mitomycin C, followed by injection of gelatin sponge particles (1
      mm pieces). Perfusion measurements (arterial and portal) were done by dynamic
      computed tomography (CT). Arterial perfusion was increased two to six days after
      TAE (0.146 +/- 0.073 ml/min/ml, P < 0.0002) compared with that before TAE (0.064
      +/- 0.039), but decreased again one month after TAE (0.086 +/- 0.038). Portal
      perfusion was decreased two to six days after TAE (0.541 +/- 0.180, P < 0.001)
      compared with that before TAE (0.733 +/- 0.263) and was grossly unchanged one
      month after TAE (0.651 +/- 0.214). We suspected that these perfusion changes were
      due to acute inflammatory responses. Quantification of tissue perfusion by
      dynamic CT was useful for studying hemodynamic changes after TAE.

PMID- 9512125
TI  - Pancreatic tuberculosis mimicking pancreatic carcinoma: four case reports and
      review of the literature.

PMID- 9512126
TI  - Metastasis from choriocarcinoma of the mediastinum producing acute appendicitis.

PMID- 9512127
TI  - Human gallbladder mucosal function: effects on intraluminal fluid and lipid
      composition in health and disease.
AB  - Gallbladder mucosal absorption of fluid during fasting is a well-known process.
      Indirect in vivo and recent in vitro evidence for physiologically relevant
      gallbladder absorption of cholesterol and phospholipids from bile has been
      observed in humans. The present study explored and compared by indirect means the
      relative efficiences of human gallbladder mucosal absorption of fluid and lipids
      in health and disease. Biliary lipids and pigment content were measured in
      fasting gallbladder bile samples obtained from gallstone-free controls and from
      four study groups: multiple and solitary cholesterol gallstone patients, and
      morbidly obese subjects with and without gallstones. Bile salts and pigment
      content were significantly greater in gallstone-free controls than in all other
      disease study groups. This was interpreted as evidence of more effective
      gallbladder mucosal fluid absorption in nonobese gallstone-free controls compared
      to that in all other groups. Correlation plot analyses of biliary lipids showed
      lower concentrations of phospholipids than expected from the index bile salt
      concentrations. The same was found for cholesterol concentrations but only in
      supersaturated samples. These findings were much more pronounced in gallstone
      free-controls and were accordingly interpreted as evidence of more efficient
      gallbladder absorption of both phospholipids and cholesterol in controls compared
      with that found in each of the disease study groups. Moreover, impaired
      gallbladder mucosal function, while invariably associated with cholesterol
      gallstone disease, was not found to be a necessary consequence of the physical
      presence of stones. It is concluded that efficient gallbladder mucosal absorption
      of both fluid and apolar lipids from bile is a normal physiological process that
      is often seriously impaired in the presence of either cholesterol gallstone
      disease or at least one of its precursor forms.

PMID- 9512128
TI  - Gallbladder volume: comparison of diabetics and controls.
AB  - Diabetics are known to have an increased prevalence of gallstones. The aim of
      this study was to investigate whether diabetics have increased gallbladder
      volumes that would predispose to stasis, nucleation of cholesterol crystals, and
      gallstone formation. The gallbladder volume of 271 diabetic subjects and 277
      controls was determined by ultrasound using the ellipse formula. Gallbladder
      volume was also determined by the sum of the cylinders method in 143 cases with a
      strong correlation (r = 0.89) between the two methods. Using analysis of
      variance, gallbladder volume was influenced by both diabetic type (NIDDM = 33.68
      cm3, IDDM = 26.84 cm3, controls = 29.05 cm3; P = 0.018) and the presence of
      gallstones (gallstones = 32.04 cm3, no gallstones = 27.58 cm3; P = 0.018). The
      variation in gallbladder volume between NIDDM, IDDM, and control subjects was
      influenced by the presence of gallstones (P = 0.024, interaction term from
      ANOVA). Significant differences (P < 0.001) were only found between NIDDM vs IDDM
      and NIDDM vs control in the nongallstone group (NIDDM = 34.33 cm3, IDDM = 25.08
      cm3, control = 25.17 cm3). Males had significantly larger gallbladder volumes
      than females: 31.98 cm3 vs 27.74 cm3 (P = 0.023). After the inclusion of BMI, HDL
      cholesterol, triglyceride, and age in a statistical model with gender and
      diabetic type in those without gallstones, significant differences were still
      found between NIDDM and IDDM (P = 0.013) and NIDDM and controls (P = 0.005),
      demonstrating that NIDDM is an independent predictor for increased gallbladder
      volume.

PMID- 9512129
TI  - Dissolution of gallstones with simvastatin, an HMG CoA reductase inhibitor.
AB  - The aim of this study was to determine whether 12 months of therapy with
      Simvastatin, an HMG CoA reductase inhibitor, would dissolve gallstones. Twenty
      seven subjects entered the study, all had a fasting oral cholecystogram,
      ultrasound examination, and fasting serum lipids prior to therapy. In addition,
      22 subjects had their gallbladder ejection fraction, after CCK, determined by
      radionucleotide scanning. Eleven subjects had the cholesterol saturation index
      (CSI) of bile calculated before and at the end of 12 months of therapy. Of the 27
      subjects, 26 completed 12 months of treatment with Simvastatin 20 mg daily. There
      was a significant fall in the total serum cholesterol (27%, P < 0.0001), LDL
      cholesterol (31%, P < 0.0001), triglyceride (34%, P < 0.0001) but no change in
      HDL after 12 months of therapy. Simvastatin treatment resulted in a 28% fall in
      the CSI of bile at the end of therapy (P < 0.01). The concentrations of
      individual bile acids did not change with therapy, and apart from a slight but
      significant increase in arachidonate, there were no other significant changes in
      the fatty acid composition of the biliary phospholipids. After 12 months of
      Simvastatin therapy there was a small decrease in the gallstone diameter but
      complete dissolution of gallstones was not achieved in any subjects. In
      conclusion 12 months of therapy with Simvastatin was effective in lowering the
      serum lipids and the CSI of bile but was not effective in dissolving gallstones.

PMID- 9512130
TI  - Portal hemodynamics by duplex Doppler sonography in different grades of
      cirrhosis.
AB  - Not much is known about the relationship between portal hemodynamics and the
      grades of cirrhosis. Using pulsed Doppler ultrasonography, we studied portal vein
      diameter, portal flow velocity, and portal blood flow rate in 37 patients with
      liver cirrhosis (11 Child's A, 13 Child's B, and 13 Child's C) and 10 healthy
      controls. There was no difference in the maximum inner diameter of the portal
      vein in cirrhotics and controls. However, there was a significant decrease in the
      portal flow velocity in patients with Child's C cirrhosis, as compared to
      controls and patients with Child's A and Child's B cirrhosis. The portal blood
      flow rate in Child's B and Child's C cirrhosis was also significantly less as
      compared to controls and patients with Child's A cirrhosis. Patients with ascites
      and encephalopathy had significantly lower portal flow velocities and blood flow
      rate as compared to those without ascites and encephalopathy, respectively. This
      study indicates that portal flow significantly decreased in cirrhotic patients
      with worsening Child's grade of cirrhosis.

PMID- 9512131
TI  - Hemodynamic effects of eight-day octreotide and propranolol administration in
      portal hypertensive rats.
AB  - Octreotide and propranolol are both effective portal hypotensive drugs in the
      control or prevention of variceal bleeding. The present study was undertaken to
      investigate the hemodynamic effects of octreotide and propranolol, alone or in
      combination, in portal hypertensive rats. Portal hypertension was induced by
      partial portal vein ligation. Portal hypertensive rats were allocated into one of
      the four groups: vehicle group (saline, 0.5 ml/day), octreotide group (100
      microg/kg/12 hr), propranolol group (30 mg/kg/day), and octreotide (100
      microg/kg/12 hr) plus propranolol (30 mg/kg/day) group. Propranolol or saline was
      administered by gavage, octreotide by subcutaneous injection. Drug was given one
      day before ligation and continued for eight consecutive days. Systemic as well as
      splanchnic hemodynamic parameters were measured thereafter. The portal venous
      pressure, portal tributary blood flow, and cardiac index were significantly
      reduced by octreotide, propranolol, or octreotide plus propranolol in portal
      hypertensive rats. Portal territory, systemic, and renal vascular resistances
      were significantly enhanced, while hepatic arterial blood flow significantly
      reduced, in the octreotide and octreotide plus propranolol groups as compared to
      vehicle group. Our results showed that eight-day administration of octreotide,
      propranolol, or octreotide plus propranolol led to portal hypotensive and
      antihyperdynamic effects in portal hypertensive rats. Overall, octreotide
      treatment alone resulted in better antihyperdynamic profiles than propranolol
      treatment alone. The combination of octreotide and propranolol offered no
      therapeutic benefits and was slightly less effective than octreotide alone.

PMID- 9512132
TI  - Transient cortical blindness in liver cirrhosis.

PMID- 9512133
TI  - The two different states of hepatitis B virus DNA in asymptomatic carriers: HBe
      antigen-positive versus anti-HBe-positive asymptomatic carriers.
AB  - During the course of hepatitis B virus (HBV) infection, there exists a long
      period of normal liver function tests with different states of HBeAg/Ab. As the
      state of HBV in asymptomatic carriers was not well characterized, we
      quantitatively and qualitatively examined HBV in both HBeAg-positive and anti-HBe
      positive asymptomatic carriers. Sera from 10 HBeAg-positive and 27 anti-HBe
      positive asymptomatic carriers were analyzed. The amount of HBV DNA was
      determined by dot-blot hybridization and polymerase chain reaction. The mutations
      in precore and core regions, spanning 636 nucleotides, of hepatitis B virus were
      examined by directly sequencing the amplified HBV DNA. HBV DNA was detected in
      all 10 HBeAg-positive cases, whereas it was found in only 7 of 27 (26%) anti-HBe
      positive cases by the nested PCR method. The mean amount of HBV DNA in HBeAg
      positive cases was 10(9.1 +/- 0.7) copies/ml, while that in anti-HBe-positive
      cases was 10(1.0 +/- 1.5) copies/ml. There were no missense mutations in the
      entire precore and core genes of HBV DNA taken from HBeAg-positive asymptomatic
      carriers. In contrast, many mutations (mean 9.0 +/- 3.3, range 6-14) were
      detected in the core gene of seven anti-HBe-positive asymptomatic carriers
      including two cases with increments of the mutations. Analysis of the precore
      region revealed three wild-type and four mutant-type (including one coexisting
      with wild-type) cases. These data suggest that HBV exists in quite different ways
      in "asymptomatic" carriers; in the HBeAg-positive phase HBV probably coexists
      with the host and remains as the wild type, whereas in the anti-HBe-positive
      phase a drastically reduced amount of HBV with many mutations remains, probably
      as a consequence of the long-lasting interaction with the host. Nevertheless,
      such small amount of virus could cause fulminant hepatic failure. It is important
      to make further clinical and virological investigations in order to understand
      the state of asymptomatic carrier.

PMID- 9512134
TI  - Different constitution of hepatitis C virus population in peripheral blood
      mononuclear cells and plasma in patients with type C chronic liver disease.
AB  - We searched for the presence of the plus or minus strand of hepatitis C virus
      (HCV) RNA in peripheral blood mononuclear cells (PBMCs) from three patients with
      chronic HCV infection using the strand-specific reverse transcription and
      polymerase chain reaction (RT-PCR) method. To examine whether the HCV population
      of PBMCs differs from that of plasma, a sequence of the hypervariable region
      (HVR) in the E2/NS1 region was analyzed. All three patients had both plus and
      minus strands of HCV RNA in their PBMCs. Sequence study revealed that the HCV
      population in PBMCs was homogeneous in all patients, while that in plasma was
      composed of two main clones. One of these had the same sequence as the clones
      seen in PBMCs, except for one patient. Our results suggest that PBMCs represent
      one of the extrahepatic replication sites of HCV and that tissue tropism is
      expressed by some of the HCV population.

PMID- 9512135
TI  - Comparison of HCV RNA levels by branched DNA probe assay and by competitive
      polymerase chain reaction to predict effectiveness of interferon treatment for
      patients with chronic hepatitis C virus.
AB  - To compare hepatitis C virus (HCV) RNA levels determined by branched DNA probe
      assay and by competitive polymerase chain reaction (PCR) as predictive markers of
      the response to interferon for treatment of patients with chronic HCV infection,
      we studied data on 140 patients treated for six months with natural interferon
      alpha. Serum samples were tested for HCV RNA by PCR. HCV RNA was grouped into
      four genotypes by PCR with type-specific primers, and HCV RNA level was measured
      by branched DNA probe assay and by competitive PCR. HCV RNA was detected in all
      patients prior to initiation of the treatment. A complete response, sustained
      elimination of HCV RNA, occurred in 51 patients (36.4%). With multiple logistic
      regression analysis assessment, when using competitive PCR, a low level of HCV
      RNA (P < 0.0001), younger age (P = 0.0054) and genotype 2a and 2b (P < 0.0158)
      were significant predictive markers for a complete response to interferon
      treatment. When using branched DNA probe assay, a low level of HCV RNA (P <
      0.0001) and age (P = 0.0089) were predictive markers, but genotype was not. The
      branched DNA probe assay had a narrower linear range for quantitation of HCV RNA
      level than competitive PCR. In conclusion, HCV RNA level determined by branched
      DNA probe assay proved to be useful for prediction of effects of interferon and
      it is cost effective as a marker of complete response to interferon treatment for
      patients with chronic HCV infection.

PMID- 9512136
TI  - Idiopathic neonatal hepatitis presenting as neonatal hepatic siderosis and
      steatosis.
AB  - Idiopathic neonatal hepatitis (INH) is a heterogeneous disease of undetermined
      cause. We report a retrospective histologic reevaluation of INH. Sixty patients
      with INH were reviewed along with 32 biliary atresia (BA) patients. Histologic
      findings, iron and fat deposits, giant cell transformation, portal fibrosis, and
      bile duct proliferation were semiquantitatively graded from 0 to 4+. Significant
      histologic findings were defined as > or =2+. Frequencies of patients with
      significant histologic findings in the INH group were compared with those of the
      BA group. Among the patients with significant histologic findings, those in the
      INH group had significantly less iron deposits (P < 0.01), portal fibrosis (P <
      0.01), and bile duct proliferation (P < 0.01) than those of the BA group. A
      combination of significant hepatic macrovesicular steatosis and siderosis was
      observed in 10 INH patients but not in any BA patient (10/60 vs 0/32, P < 0.05).
      Without extensive treatment, the 10 INH patients all recovered, and hepatic
      abnormalities normalized by the age of 12 months. In conclusion, the present
      study showed that the recognition of hepatic siderosis is helpful to distinguish
      BA from INH and that in a subset of INH patients hepatic macrovesicular steatosis
      and siderosis occurs.

PMID- 9512137
TI  - Segmental absence of intestinal musculature in an adult.

PMID- 9512138
TI  - Quality of life in persons with irritable bowel syndrome: development and
      validation of a new measure.
AB  - How irritable bowel syndrome (IBS) and its treatment affect quality of life (QOL)
      is important. To develop a quality-of-life measure specific to irritable bowel
      syndrome, items were generated using a conceptual model and qualitative
      interviews with persons diagnosed using the Rome criteria. Symptom frequency and
      bothersomeness indices were created. Psychometric evaluation methods involved an
      initial cross-sectional survey followed by a repeat survey. The resulting 34-item
      measure demonstrated high internal consistency (Cronbach's alpha = 0.95) and high
      reproducibility (ICC = 0.86) with average time of seven days (SD = 1). For
      discriminant validity: number of symptoms (P < 0.05), self-reported severity of
      symptoms (P < 0.001), and the functional bowel disorder severity index (P <
      0.001) significantly predicted IBS-QOL scores. Convergent validity and analyses
      confirmed predictions that scores are more closely related to psychological well
      being (0.45) than to function (0.36). We conclude this measure meets established
      psychometric criteria for reliability and validity; testing of its responsiveness
      is warranted.

PMID- 9512139
TI  - Crohn's disease stable remission after human immunodeficiency virus infection.
AB  - We retrospectively assessed the clinical course in four patients with long
      standing Crohn's disease who became infected with human immunodeficiency virus
      (HIV). The duration of active Crohn's disease was 21, 10, 4, and 4 years in our
      four patients. They experienced a stable remission of Crohn's disease symptoms
      after HIV infection. In three patients Crohn's disease was in stable remission
      for 5, 8, and 8 years after HIV infection and all three died from acquired
      immunodeficiency syndrome-related disease. One patient was still alive without
      recurrence of Crohn's disease symptoms 7 years following HIV detection. Our
      observations of a spontaneous improvement in the clinical course of Crohn's
      disease after HIV infection, suggests that the integrity of the immune response,
      especially that of CD4 T cells, plays a major role in the tissue injury mechanism
      in Crohn's disease.

PMID- 9512140
TI  - Disseminated aseptic abscesses associated with Crohn's disease: a new entity?
AB  - Our purpose is to describe seven cases of disseminated aseptic abscesses with
      regard to clinical, biological, radiological, and histological information,
      treatment, and outcome. Data were collected on seven Caucasian patients who had
      proven sterile deep abscesses diagnosed in French university hospitals. The onset
      of the disease related to abscesses began at times from June 1988 to August 1994.
      Follow-up periods were 1 year, 7 months to 8 years, 2 months. The age of the
      patients ranged from 15 to 26 years old. At onset, all had fever and six had
      abdominal pain. Abscesses involved spleen and abdominal lymph nodes in six cases;
      liver in three; pancreas, brain, and chest in one. All had polymorphonuclear
      leukocytosis. Pathological examination showed granulomatous abscesses. Direct and
      indirect investigations failed to identify any causal microorganism. On six
      occasions, Crohn's disease was revealed 1 to 41 months later and in one case, it
      preceded the onset of abscesses. One subsequently developed Sweet's syndrome.
      Various antibiotic regimes were inefficient. Steroids, associated in three cases
      with immunosuppressive agents, resulted in a rapid improvement in six patients.
      In one case, splenectomy followed by 5-ASA therapy was used successfully. The
      dramatic effectiveness of steroids and immunosuppressive agents as well as follow
      up suggest that disseminated aseptic abscesses might be an extraintestinal
      manifestation of Crohn's disease. Although the pathogenesis of this condition
      remains unknown, this entity may be related to neutrophilic dermatosis in which
      sterile deep abscesses have been reported.

PMID- 9512141
TI  - Preoperative perfusion of bypassed ileum does not improve postoperative function.
AB  - This study evaluated whether twice daily isotonic perfusion of the bypassed ileum
      for six weeks would enhance its motor activity and its absorption of fluids,
      electrolytes, and vitamin B12. The study also determined if patients undergoing
      perfusion had improved bowel function and decreased hospital stay after ileostomy
      closure. Following proctocolectomy, ileal pouch-anal canal anastomosis, and
      diverting loop ileostomy, six patients self-infused an isotonic solution (sucrose
      and sodium chloride) into the bypassed ileum twice daily, while seven patients
      did not (controls). Two months following proctocolectomy, and just prior to
      ileostomy closure, a manometric catheter assembly was placed into the unused
      distal ileum via the stoma and the distal ileum perfused with an isotonic sodium
      chloride solution for 3 hr during fasting and 3 hr after a meal. Absorption was
      measured, single and clustered pressure waves were identified, and a motility
      index was calculated. Water absorption, motility index, and cluster parameters
      did not improve in perfused patients compared to controls during fasting or after
      a meal, nor did perfused patients have improved vitamin B12 absorption. The
      perfused patients also did no better clinically following ileostomy takedown; the
      onset of bowel movements, their frequency, time to tolerate a diet, and hospital
      stay were similar to controls. We conclude that six weeks of twice daily isotonic
      perfusion did not improve motor activity or water, electrolyte, and vitamin B12
      absorption in the bypassed distal ileum after proctocolectomy, ileal pouch-anal
      canal anastomosis, and loop ileostomy. The perfusion also did not improve bowel
      function after ileostomy takedown.

PMID- 9512142
TI  - In vivo and in vitro efficacy of octreotide for treatment of enteric
      cryptosporidiosis.
AB  - Previous evidence suggested a role of enterotoxin in the pathophysiology of
      cryptosporidiosis. If so, antisecretory drugs should be effective in reducing
      diarrhea. We evaluated the in vivo and in vitro efficacy of octreotide, which
      possesses antisecretory effects, for cryptosporidial diarrhea. Two children with
      severe cryptosporidial diarrhea were treated with octreotide. The volume
      modifications and chemical composition of stools were determined. Fecal
      supernatant was added to Caco-2 cell monolayers mounted in Ussing chambers with
      or without serosal octreotide and electrical parameters were monitored.
      Octreotide was effective in reducing the stool volume and fecal Na+
      concentration. Fecal supernatant induced an enterotoxin-like increase in
      transepithelial potential difference. Octreotide induced a dose-dependent
      decrease in basal potential difference, consistent with an absorptive effect. In
      cells pretreated with octreotide, fecal supernatant induced an increase in the
      potential difference, whose magnitude and duration were significantly reduced
      compared to untreated cells. These results provide in vivo and in vitro evidence
      for the secretory nature of cryptosporidial diarrhea and for the efficacy of
      octreotide through a direct interaction with the enterocyte.

PMID- 9512143
TI  - Interleukin-6 and small intestinal luminal immunoglobulins.
AB  - Our aim was to determine the relationships between interleukin-6 and
      immunoglobulin levels within small intestinal luminal secretions. Twenty adult
      subjects with small intestinal bacterial overgrowth (N = 13), irritable bowel
      syndrome (N = 4), and nonulcer dyspepsia (N = 3) underwent endoscopic aspiration
      of secretions from the small intestinal mucosal surface for assessment of IL-6,
      IgA1, IgA2, IgM, IgG1, IgG2, IgG3, and IgG4 concentrations. Serum immunoglobulin
      concentrations and small intestinal histology were also determined. IgA2 and IgG3
      were the predominant IgA and IgG subclasses in luminal secretions in 19/20 (95%)
      and 20/20 (100%) subjects, respectively. IgA1 and IgG1 predominated in serum in
      all subjects. No subject had villous atrophy. Luminal IL-6 concentrations
      correlated significantly with luminal IgA2, IgM, and IgG3 concentrations but not
      with IgA1 or any other IgG subclass levels. Conversely, luminal IL-6 or
      immunoglobulin concentrations did not correlate significantly with levels of any
      immunoglobulin isotype in serum. These observations suggest that important
      relationships exist between local IL-6 and IgA2, IgM, and IgG3 responses in human
      small intestinal luminal secretions. Local investigation is mandatory when
      assessing intestinal immune activity.

PMID- 9512144
TI  - Herpes zoster ophthalmicus in patients with human immunodeficiency virus
      infection.
AB  - PURPOSE: To investigate the ocular complications of herpes zoster ophthalmicus in
      patients with human immunodeficiency virus (HIV) infection. METHODS: This was a
      retrospective cohort study of 48 HIV-infected patients (48 eyes) treated at San
      Francisco General Hospital for herpes zoster ophthalmicus from December 1985
      through March 1994. RESULTS: All patients were initially treated with either
      intravenous or oral acyclovir. The median CD4 lymphocyte count at diagnosis was
      48 per mm3 (range, 2 to 490 per mm3). Fifteen patients (31%) had mild or no
      ocular involvement. Seventeen patients (35%) had stromal keratitis, mostly mild,
      and two (4)% developed chronic infectious pseudodendritic keratitis. Twenty-four
      study patients (50%) had iritis, but only three (6%) had elevations in
      intraocular pressure. Two patients (4%) developed postherpetic neuralgia, and two
      others (4%) had zoster-associated central nervous system disease. Only two
      patients (4%) developed necrotizing retinitis, both in the form of the
      progressive outer retinal necrosis syndrome. CONCLUSIONS: Excluding the patients
      with retinitis and central nervous system disease, the rate of sight-threatening
      complications in our series was lower than expected. Almost one third of study
      patients had no ocular complications or only mild surface epithelial disease.
      Although the relatively low incidence of sight-threatening disease in our study
      population may have been a consequence of aggressive management with acyclovir,
      chronic infectious pseudodendritic keratitis, retinitis, and central nervous
      system disease, complications of ophthalmic zoster whose pathogenesis is largely
      a consequence of active viral replication, were particularly devastating and
      difficult to manage.

PMID- 9512145
TI  - Transient vitreous inflammatory reactions associated with combination
      antiretroviral therapy in patients with AIDS and cytomegalovirus retinitis.
AB  - PURPOSE: To report the observation that a transient vitreous inflammatory
      reaction may develop in the eyes of patients with acquired immunodeficiency
      syndrome (AIDS), cytomegalovirus retinitis, and an increased CD4+ T-lymphocyte
      count during treatment with antiretroviral therapy including a protease
      inhibitor. METHODS: We reviewed the medical records of eight patients with AIDS
      and cytomegalovirus retinitis who developed vitreous inflammatory reactions
      greater than those usually seen with this disease. RESULTS: Vitreous inflammatory
      reactions obscured the view of the posterior pole in all patients. No iris
      nodules, synechiae, glaucoma, or cystoid macular edema were observed. Six
      patients had unilateral cytomegalovirus retinitis, and, in each, the inflammation
      occurred only in the eye with cytomegalovirus retinitis. The vitreous
      inflammatory reactions were associated with clinically inactive cytomegalovirus
      retinitis in six patients, with disease reactivation in one patient, and were
      present at diagnosis of active disease in one patient. Cytomegalovirus retinitis
      has not recurred in any of these patients since their episodes of vitreous
      inflammation. Vitreous inflammation developed in all eight patients after a
      substantial increase in CD4+ T-lymphocyte counts caused by combination
      antiretroviral therapy. Five patients had CD4+ T-lymphocyte counts of greater
      than 100 cells per microl at the time the vitreous inflammatory reaction
      developed. No other causes of uveitis were found. CONCLUSIONS: Patients with AIDS
      and cytomegalovirus retinitis may develop transient intraocular inflammation
      associated with combination antiretroviral therapy. We believe that this
      inflammation reflects an improved immune response against cytomegalovirus.

PMID- 9512146
TI  - Uveitis associated with human immunodeficiency virus infection.
AB  - PURPOSE: To report uveitis associated with human immunodeficiency virus (HIV)
      infection and to suggest guidelines for treatment. METHODS: Six HIV-seropositive
      patients (10 eyes) with anterior or posterior uveitis or both were evaluated.
      After ineffective prolonged treatment with systemic and topical corticosteroids,
      specific systemic antiretroviral therapy with zidovudine was initiated in all
      patients. Aqueous humor was cultured in three eyes of three patients, and
      vitreous humor was cultured in one eye of one patient. RESULTS: In all 10 eyes of
      six patients, there was resolution of inflammation in 10 to 42 days after
      commencement of treatment with zidovudine (600 to 800 mg/day), despite no or
      minimal response to corticosteroids. Cultures of aqueous humor from three eyes of
      three patients and culture of vitreous humor from one eye of one patient were
      positive for HIV; no other organism was isolated. Systemic evaluation disclosed
      no other identifiable cause for the uveitis in any patient. CONCLUSIONS:
      Infection with HIV appears to be a cause of uveitis. A trial of zidovudine may be
      warranted in HIV-seropositive patients with uveitis that is poorly responsive to
      corticosteroid treatment when no other cause is identified. The efficacy of other
      retroviral agents was not determined.

PMID- 9512147
TI  - Vitritis as the primary manifestation of ocular syphilis in patients with HIV
      infection.
AB  - PURPOSE: To describe dense vitritis as the primary manifestation of ocular
      syphilis in three human immunodeficiency virus (HIV)-positive patients and to
      determine the response of these patients to the established regimen for
      neurosyphilis. METHODS: Anti-Toxoplasma gondii IgM and IgG antibody titers,
      tuberculin skin test, chest radiograph, and serum angiotensin-converting enzyme
      level were obtained because tuberculosis, sarcoidosis, and toxoplasmosis were in
      the differential diagnosis. Two of the three patients were not known to have HIV
      infection at the time of initial examination and consented to HIV testing.
      Treponemal and nontreponemal tests were performed on serum and cerebrospinal
      fluid to establish a definitive diagnosis. Treatment for neurosyphilis was
      initiated, and daily ophthalmic examinations were performed, with careful
      attention to signs commonly associated with syphilitic eye disease. RESULTS: All
      three patients exhibited improvement in visual acuity and resolution of vitreous
      haze. There was no evidence of other signs of posterior uveitis. The one patient
      for whom there has been a 6-month follow-up showed no sequelae of his eye
      disease. CONCLUSIONS: Human immunodeficiency virus-positive patients with
      syphilis may present atypically dense vitritis. In these patients, vitritis may
      be the first manifestation of syphilis. The regimen for neurosyphilis provides
      effective therapy. Moreover, in some patients, syphilitic vitritis may be the
      initial manifestation of HIV disease.

PMID- 9512149
TI  - The effects of cataract extraction on the visual field of eyes with chronic open
      angle glaucoma.
AB  - PURPOSE: To investigate effects of cataract extraction and intraocular lens
      placement on the visual field of eyes with chronic open-angle glaucoma. METHODS:
      A retrospective review was conducted of 41 eyes of 41 patients with visually
      significant cataract and chronic open-angle glaucoma who had undergone automated
      static perimetry within 6 months before and 6 months after phacoemulsification
      with intraocular lens placement. RESULTS: Comparison of preoperative and
      postoperative testing showed that the mean visual acuity, foveal threshold, and
      mean deviation improved significantly (P < .0001), while the mean pattern
      standard deviation and corrected pattern standard deviation worsened
      significantly (P < or = .03). Eyes not receiving miotics preoperatively did not
      have a significant postoperative change in the mean pattern and corrected pattern
      standard deviations. Increasing severity of glaucoma-related visual field loss
      was significantly associated with less improvement in the postoperative mean
      deviation (P = .0001). Only two (5%) of 41 eyes had worsening of the mean
      deviation of 1.0 dB or greater. The foveal threshold improved more than the mean
      deviation did but not significantly more, except in eyes with severe visual field
      loss. CONCLUSIONS: Cataract extraction resulted in statistically significant
      improvement in visual acuity and foveal threshold in most eyes with glaucoma. In
      eyes with mild or moderate glaucoma-related damage, the mean deviation often
      improved significantly after cataract extraction, but improvement was less
      predictable in eyes with severe or end-stage damage. The pattern and corrected
      pattern standard deviations may be reliable indicators of glaucoma-related damage
      in eyes with cataract but without constricted pupils.

PMID- 9512148
TI  - Chronic multifocal retinal infiltrates in patients infected with human
      immunodeficiency virus.
AB  - PURPOSE: To describe the clinical features of a disorder characterized by chronic
      multifocal retinal infiltrates and uveitis in individuals with human
      immunodeficiency virus (HIV) disease. METHODS: We reviewed the medical records of
      HIV-infected patients with multifocal retinal infiltrates of unknown cause seen
      by investigators at four institutions. The following data were collected:
      demographic characteristics, presenting signs and symptoms, laboratory test
      results, and course of disease. RESULTS: We identified 26 HIV-infected patients
      (50 involved eyes) with this syndrome. Median CD4+ T-lymphocyte count at
      presentation was 272 per microl (range, 7 to 2,118 per microl). The most common
      presenting symptom was floaters. Median visual acuity of involved eyes at
      presentation was 20/20 (range, 20/15 to 20/100) and remained stable (median,
      20/20; range, 20/15 to 20/70) after a median follow-up period of 9 months (range,
      0 to 110 months). Typical retinal lesions were gray-white or yellow, irregular in
      shape, and less than 200 microm in greatest dimension. All were located in the
      midperiphery or anterior retina and enlarged slowly or remained static in size.
      Mild to moderate anterior chamber or vitreous humor inflammatory cells were
      present in 47 of 50 eyes (26 of 26 patients). Retinal lesions possibly responded
      to zidovudine but not to acyclovir or ganciclovir. Anterior chamber and vitreous
      humor inflammatory reactions responded to topical or periocular injections of
      corticosteroid. CONCLUSIONS: Uveitis with chronic multifocal retinal infiltrates
      is a distinct clinical entity of unknown cause that occurs in HIV-infected
      patients. Retinal lesions may respond to antiretroviral therapy. Visual prognosis
      is good.

PMID- 9512150
TI  - Combined trabeculectomy and phacoemulsification: a one-site vs a two-site
      approach.
AB  - PURPOSE: To compare the results of combined trabeculectomy and
      phacoemulsification surgery with intraocular lens implant by means of a one-site
      vs a two-site approach. METHODS: Glaucomatous patients with a coexisting cataract
      were randomly assigned to undergo either a one-site or two-site combined
      procedure. One-site surgery was performed with a limbus-based conjunctival flap
      and scleral tunnel at the 12-o'clock position. Two-site surgery was performed
      with a limbus-based conjunctival flap for the trabeculectomy in the superior
      nasal quadrant and a temporal clear cornea incision for phacoemulsification.
      Mitomycin C (0.4 mg/ml for 2 minutes) was applied to the scleral surface at the
      trabeculectomy site for both approaches. All patients received intraocular lens
      implants at the time of combined surgery. RESULTS: Thirty-three eyes of 33
      patients were included in this study. Preoperative intraocular pressure and
      number of glaucoma medications were similar in the two groups. Corrected visual
      acuity improved similarly in both groups. Intraocular pressure decreased in both
      groups at last follow-up but was not significantly different (P = .129) between
      the one-site and two-site groups. At last follow-up, the one-site group required
      significantly more (P = .030) medications than did the two-site group.
      CONCLUSIONS: Combined trabeculectomy and phacoemulsification surgery in which one
      site and two-site techniques were used yielded similar improvements in corrected
      visual acuity and intraocular pressure reduction. However, the one-site group
      required more medication to maintain intraocular pressure control than did the
      two-site group.

PMID- 9512151
TI  - Limbus-based vs fornix-based conjunctival flap in combined glaucoma and cataract
      surgery with adjunctive mitomycin C.
AB  - PURPOSE: To determine the efficacy and safety of limbus-based vs fornix-based
      conjunctival flaps in patients with primary open-angle glaucoma undergoing
      trabeculectomy combined with phacoemulsification and intraocular lens
      implantation with adjunctive subconjunctival mitomycin C. METHODS: In a
      prospective study, 69 eyes of 69 patients with primary open-angle glaucoma,
      visually symptomatic cataracts, and no previous incisional ocular surgery were
      randomly assigned to limbus-based and fornix-based conjunctival flap groups. All
      patients received trabeculectomy combined with phacoemulsification and posterior
      chamber lens implantation with 1-minute (0.5 mg/ ml) application of
      subconjunctival mitomycin C. RESULTS: The mean intraocular pressures were
      significantly (P < .05) lower on significantly (P < .05) fewer medications
      postoperatively at 1 week, 1 month, 3, 6, 9, 12, and 15 to 18 months, and at last
      follow-up in both groups than they had been preoperatively. However, there were
      no significant (P > .05) differences in postoperative mean intraocular pressure,
      mean number of medications, and visual acuity between the two groups at any time
      interval. Hypotony with wound leak was significantly (P = .019) higher in the
      limbus-based group. Other postoperative complications were not significantly (P >
      .05) different between the two groups. CONCLUSIONS: There was no notable
      difference in glaucoma control or visual outcome between limbus-based and fornix
      based conjunctival flaps in primary trabeculectomy combined with
      phacoemulsification and lens implantation with adjunctive subconjunctival
      mitomycin C. The fornix-based flap was as safe as, if not safer than, the limbus
      based flap in the glaucoma triple procedure with adjunctive subconjunctival
      mitomycin C.

PMID- 9512152
TI  - Primary glaucoma triple procedure in patients with primary open-angle glaucoma:
      the effect of mitomycin C in patients with and without prognostic factors for
      filtration failure.
AB  - PURPOSE: To investigate the effect of adjunctive mitomycin C on primary glaucoma
      triple procedure in patients with primary open-angle glaucoma with and without
      one or more of the prognostic factors for filtration failure of primary glaucoma
      triple procedure. Those factors include being of African-American race, having a
      preoperative intraocular pressure of 20 mm Hg or more on maximum tolerated
      medications, and being on two or more medications preoperatively. METHODS: Study
      patients consisted of 197 consecutive patients with primary open-angle glaucoma
      who were randomly assigned to receive either no adjunctive mitomycin C (101 eyes
      of 101 patients) or to receive adjunctive subconjunctival mitomycin C (96 eyes of
      96 patients) during the primary glaucoma triple procedure. Kaplan-Meier survival
      analysis comparisons were made between respective subgroups with and without
      prognostic indicators for filtration failures using a relatively stringent set of
      criteria for filtration success of primary glaucoma triple procedure. RESULTS:
      There was no statistically significant (P = .117) difference in filtration
      success of primary glaucoma triple procedure between the control and mitomycin C
      groups. Adjunctive mitomycin C significantly (P < .05) improved the filtration
      outcome of the primary glaucoma triple procedure in the subgroups with each of
      the three prognostic factors for filtration failure of primary glaucoma triple
      procedure. On the other hand, in the subgroups without the prognostic factors,
      adjunctive mitomycin C did not significantly (P > .05) change the filtration
      outcome of the primary glaucoma triple procedure. CONCLUSION: These findings
      establish the basis for selective use of mitomycin C in patients with primary
      open-angle glaucoma undergoing primary glaucoma triple procedure.

PMID- 9512154
TI  - The natural history of macular pseudoholes.
AB  - PURPOSE: To report the natural history of macular pseudoholes with regard to
      ophthalmoscopic appearance and visual acuity. METHODS: Thirty-six eyes of 34
      patients with macular pseudoholes who were followed up for 1 year or longer were
      retrospectively evaluated to compare the initial ophthalmoscopic appearance and
      visual acuity with the most recent follow-up appearance and visual acuity.
      RESULTS: Mean visual acuity at initial examination was 20/32 (median, 20/30);
      mean follow-up visual acuity was 20/32 (median, 20/30). Fourteen eyes (39%) had
      identical initial and final visual acuities, and 30 eyes (83%) had final visual
      acuity within 2 lines on the visual acuity chart from their initial examination.
      Four eyes had improved visual acuity of more than 2 lines, and two eyes lost more
      than 2 lines of visual acuity. Thirty-one eyes had adequate initial and follow-up
      photographs allowing comparison of macular appearance. Twenty-three (74%) of the
      31 eyes showed a definitive change in macular appearance. CONCLUSIONS: Visual
      acuity in patients with macular pseudoholes tended to remain stable. However, the
      macular appearance changed in 74% of eyes.

PMID- 9512153
TI  - The epsilon4 allele of the apolipoprotein E gene as a potential protective factor
      for exudative age-related macular degeneration.
AB  - PURPOSE: Apolipoprotein E (ApoE) is a polymorphic protein that plays a central
      part in plasma metabolism of lipids and in central nervous system lipid
      homeostasis. Our purpose was to evaluate the potential role of ApoE polymorphism
      in the occurrence of exudative age-related macular degeneration associated with
      drusen, which contain lipids. METHODS: We analyzed apolipoprotein E genotypes in
      116 unrelated patients with exudative age-related macular degeneration in one eye
      and hard drusen (n = 39) or soft drusen (n = 77) in the other eye, and compared
      the results with those of age-matched and sex-matched control subjects (n = 168).
      Apolipoprotein E alleles were detected by a ploymerase chain reaction-based
      method. RESULTS: A lower frequency of the epsilon4 allele carriers was observed
      in the exudative age-related macular degeneration group compared with control
      subjects (12.1% vs 28.6%, respectively; P < .0009). The epsilon4 allele was less
      frequent in the age-related macular degeneration group compared with control
      subjects (0.073 vs 0.149, respectively; P < .006). This decreased frequency of
      the epsilon4 allele was mainly observed in the soft drusen subgroup compared with
      control subjects (0.045 vs 0.149, respectively; P < .0009). CONCLUSION: This
      lower relative frequency of the epsilon4 allele supports the hypothesis that the
      ApoE gene is a genetic protective factor identified in age-related macular
      degeneration.

PMID- 9512155
TI  - Radiation choroidopathy with remodeling of the choroidal venous system.
AB  - PURPOSE: To describe a case of radiation choroidopathy manifesting drastic
      remodeling of choroidal drainage routes. METHOD: Case report. A 34-year-old man
      who had received radiation treatment for a tumor in the upper eyelid of his right
      eye 15 years earlier had floating black spots. He was examined
      ophthalmologically, including with indocyanine green angiography using a scanning
      laser ophthalmoscope. RESULTS: The right eye manifested classic features of
      radiation retinopathy in the superior fundus. Indocyanine green angiography
      showed vaso-occlusion of choroidal arteries, capillaries, and veins in a wider
      area than that affected by radiation retinopathy. The superotemporal vortex vein
      was obliterated, resulting in a remodeling of the choroidal veins in the same
      quadrant. The blood in this quadrant drained into the inferotemporal vortex vein
      through collateral venovenous drainage routes. CONCLUSION: The diagnosis in this
      eye was radiation retinopathy and radiation choroidopathy. Choroidal vascular
      lesions were more pronounced and involved a wider area than retinal vascular
      lesions did. This case illustrates that the choroidal veins may manifest a vast
      plasticity to remodel the drainage route after obliteration of a major vortex
      vein.

PMID- 9512156
TI  - Human immunodeficiency virus disease: changing patterns of intraocular
      inflammation.
AB  - PURPOSE: To evaluate and put into perspective five articles in this issue of the
      AMERICAN JOURNAL OF OPHTHALMOLOGY that discuss ocular inflammatory disorders in
      patients with human immunodeficiency virus (HIV) disease. METHODS: We drew upon
      recent observations concerning the effect of HIV disease on the immune system in
      an attempt to understand the current reports describing intraocular inflammation.
      RESULTS: Intraocular inflammation appears to be dependent on several factors,
      including specific antigenic stimuli and the state of the host immune system.
      During dynamic changes in these factors, conditions may arise that favor
      inflammatory reactions. Use of antiretroviral therapies is one mechanism that can
      effect these dynamics. CONCLUSIONS: As the immune system equilibrates at one
      extreme or the other (depletion or reconstitution), conditions favoring
      inflammation appear to dissipate. Restoration of immune function by the use of
      combination antiretroviral therapy, including protease inhibitors, may lead to
      additional cases of transient intraocular inflammation in the future.

PMID- 9512157
TI  - Pieces of a puzzle: Toward a better understanding of intraocular inflammation
      associated with human immunodeficiency virus disease.

PMID- 9512158
TI  - Viscosity-dependent fluid dynamics of eyedrops on the ocular surface.
AB  - PURPOSE: To determine whether the viscosity of eyedrops affects the distribution
      of the precorneal tear film. METHODS: Using a differential pachymetry map, we
      obtained tear film thickness in healthy volunteers before and after the
      instillation of nonviscous, aqueous artificial tears and a 0.3% sodium
      hyaluronate solution. RESULTS: The instillation of aqueous artificial tears
      disclosed a significant (P < .05) thickening of the superior corneal tear film
      compared with the inferior corneal tear film. The increase in thickness by 0.3%
      sodium hyaluronate solution was uniform, with no differences between the superior
      and inferior cornea. CONCLUSIONS: Aqueous artificial tears caused an uneven
      thickening of the precorneal tear film, with most of the thickening observed at
      the superior cornea. Lower sections of the cornea may benefit less from the
      instillation of nonviscous solutions.

PMID- 9512159
TI  - Real-time telemedicine in the clinical assessment of the ocular surface.
AB  - PURPOSE: To report the feasibility of real-time video and audio transmission of
      slit-lamp images of the eye using conventional telephone systems. METHOD: We
      analyzed the feasibility and benefits of telemedicine in the diagnosis and follow
      up of ocular surface disorders in referral patients using a real-time audio-video
      system that functions through integrated services digital network lines at a
      transmission speed of 384 kilobytes per second. RESULTS: Real-time slit-lamp
      images obtained through integrated services digital network lines offered
      satisfactory visual resolution of the ocular surface for the diagnosis and follow
      up of ocular surface and corneal disease, while simultaneous audio transmission
      allowed for direct communication with the patient and attending physician when
      necessary. CONCLUSION: Telemedicine using conventional telecommunication
      infrastructures offers sufficient information for the diagnosis and follow-up of
      ocular surface disorders in referral patients.

PMID- 9512160
TI  - Corneal injury from explosion of microwaved eggs.
AB  - PURPOSE: To report two patients with ocular burns from explosion of microwaved
      eggs that caused direct vision-threatening corneal damage. METHODS: The initial
      examination and treatment of both patients are described. RESULTS: Both patients
      were initially examined with severe decrease in the visual acuity of both eyes.
      The first patient required limbal conjunctival transplantation and a subsequent
      penetrating keratoplasty in the right eye and prolonged treatment of superficial
      keratitis in the left eye. The second patient sustained bilateral corneal
      epithelial defects and unilateral intrastromal hemorrhage. CONCLUSIONS: Exploding
      microwaved eggs can cause notable thermal injury to the eyes. The public should
      be educated about the dangers of cooking eggs in the microwave oven.

PMID- 9512161
TI  - Corneal injury after carbon dioxide laser skin resurfacing.
AB  - PURPOSE: To describe a corneal injury in both eyes of a patient who had undergone
      carbon dioxide laser skin resurfacing. METHOD: Case report. RESULTS: A 67-year
      old woman had severe pain and decreased vision in both eyes after undergoing
      laser skin resurfacing treatment with a pulsed carbon dioxide laser. Clinical
      examination disclosed a corneal ulcer, a bullous keratopathy, and intrastromal
      bleeding. After perforating keratoplasty, the histologic examination of the
      cornea showed signs of thermal injury. CONCLUSIONS: The results of the histologic
      examination and the onset of symptoms within 24 hours after therapy suggest that
      the laser application caused the corneal damage. Safety guidelines for this
      procedure should be reviewed.

PMID- 9512162
TI  - Epibulbar molluscum contagiosum.
AB  - PURPOSE: To report a case of epibulbar conjunctival nodules from molluscum
      contagiosum in a patient with atopic dermatitis. METHODS: A 39-year-old man with
      atopic dermatitis who was treated with oral prednisone was initially examined
      with ocular itching, foreign body sensation, and conjunctival injection of the
      right eye and was found to have three discrete conjunctival nodules. Excision of
      the nodules led to complete resolution of the signs and symptoms. RESULT:
      Histopathologic examination of the conjunctival specimen disclosed molluscum
      contagiosum. CONCLUSION: Patients with defective or suppressed cell-mediated
      immunity are at increased risk of unusual ocular involvement with molluscum
      contagiosum.

PMID- 9512163
TI  - Minocycline-induced scleral, dental, and dermal pigmentation.
AB  - PURPOSE: To report a case of scleral discoloration secondary to minocycline
      therapy. METHOD: Case report of a patient referred to a university-based cornea
      and external disease clinic. RESULTS: The patient had been treated with oral
      minocycline therapy for adult facial acne for 12 years when she began to develop
      bilateral blue-gray discoloration of the sclera as well as of the teeth, hard
      palate, ears, nail beds, and skin. CONCLUSIONS: Chronic systemic minocycline
      therapy may induce scleral pigmentary changes. The mechanism of discoloration and
      the long-term natural history upon cessation of minocycline are unclear.

PMID- 9512164
TI  - Gillespie syndrome phenotype with a t(X;11)(p22.32;p12) de novo translocation.
AB  - PURPOSE: To report a patient with a phenotype suggestive of Gillespie syndrome
      and with a chromosomal abnormality. METHODS: Clinical evaluation showed bilateral
      superior coloboma, foveal hypoplasia, and inferior cerebellar hypoplasia.
      Karyotyping as well as investigation of the PAX6 gene were performed. RESULTS:
      The karyotype of the patient disclosed a de novo translocation
      t(X;11)(p22.32;p12). Fluorescent in situ hybridization and the search for
      mutations excluded direct implication of the PAX6 gene. CONCLUSION: This is, to
      our knowledge, the first report of a chromosomal abnormality detected in a
      patient with a Gillespie syndrome phenotype.

PMID- 9512165
TI  - Absence of the abducens nerve in Duane syndrome verified by magnetic resonance
      imaging.
AB  - PURPOSE: To demonstrate that currently available magnetic resonance imaging
      techniques may verify the absence of the abducens nerve in Duane syndrome.
      METHODS: We performed magnetic resonance imaging in a 36-year-old woman with left
      Duane syndrome, type 1, using spoiled gradient recalled acquisition in the steady
      state to obtain high-resolution T1-weighted images through the abducens nerve in
      its subarachnoid segment. Scans were obtained in the axial plane from the medulla
      to the midbrain and then reformatted along the plane of the abducens nerve.
      RESULT: Unilateral absence of the left abducens nerve was verified using magnetic
      resonance imaging. CONCLUSION: The absence of the abducens nerve in Duane
      syndrome can be verified by modern magnetic resonance imaging techniques.

PMID- 9512166
TI  - Small retinal hemorrhages as the only sign of an intracranial aneurysm.
AB  - PURPOSE: To report a woman with two small circumpapillary and nerve fiber layer
      hemorrhages found on routine examination. METHODS: Case report. The patient had a
      history of severe headache 2 weeks previously but no other symptoms or signs.
      RESULT: Magnetic resonance imaging showed an intracranial aneurysm. CONCLUSIONS:
      This potentially lethal abnormality should be considered with small unexplained
      retinal hemorrhages, even when the neurologic examination is normal. A history of
      recent headache should be sought.

PMID- 9512167
TI  - Immunoadsorption therapy for Fisher syndrome associated with IgG anti-GQ1b
      antibody.
AB  - PURPOSE: To describe the effects of immunoadsorption therapy with a tryptophan
      immobilized column on Fisher syndrome associated with IgG anti-GQ1b ganglioside
      antibody. METHODS: Three patients with Fisher syndrome and with a high serum IgG
      anti-GQ1b antibody titer underwent four to nine sessions of immunoadsorption
      therapy with a tryptophan-immobilized column. Using enzyme-linked immunosorbent
      assay (ELISA), we determined the differences in IgG anti-GQ1b antibody titers.
      RESULTS: ELISA disclosed that the IgG anti-GQ1b antibody titers of the serum
      samples collected from the inlet of the column were markedly higher than those
      collected from the outlet for all three patients. Moreover, after completion of
      the immunoadsorption therapy, the patients' serum IgG anti-GQ1b antibody titers
      were markedly lower than they were before the immunoadsorption therapy. The
      patients' ophthalmoparesis decreased in severity during the therapy. CONCLUSION:
      These findings suggest that immunoadsorption therapy with the tryptophan
      immobilized column is an effective method for removing IgG anti-GQ1b antibody
      from serum.

PMID- 9512168
TI  - Digoxin visual toxicity with therapeutic blood levels of digoxin.
AB  - PURPOSE: To report two cases of digoxin-related visual disturbances associated
      with therapeutic blood levels of digoxin. METHODS: Case reports. One patient
      reported shimmering lights in the field of vision of both eyes; the second
      patient had a corrected visual acuity of BE, 20/40 and generalized visual field
      depression in both eyes. Both patients experienced these symptoms while receiving
      digoxin. RESULTS: Both patients had digoxin blood levels in the therapeutic range
      (1.7 and 1.0 ng/ml, respectively). Therapeutic levels are 0.5 to 2.0 ng/ml. After
      discontinuing digoxin, the first patient noted that the shimmering light symptoms
      resolved, and the second patient had improved visual acuity and visual fields.
      CONCLUSIONS: Digoxin-related visual toxicity may be associated with therapeutic
      blood levels of digoxin. Recognition of this entity may avoid unnecessary testing
      and frustration.

PMID- 9512169
TI  - Surgical removal of solitary hepatic metastasis from choroidal melanoma.
AB  - PURPOSE: To report surgical management of solitary hepatic metastasis that
      occurred 25 years after an enucleation for uveal melanoma. METHODS: A 16-year-old
      girl, diagnosed with choroidal melanoma and treated with enucleation, was found
      25 years later to have liver metastasis affecting the entire left lobe of the
      liver. RESULTS: She underwent partial hepatectomy with removal of the metastatic
      melanoma. Four years later, she was found to have a smaller circumscribed nodular
      melanoma in the remaining right lobe of the liver, also treated with resection.
      She has remained disease-free for 2 years, with no evidence of systemic disease.
      CONCLUSION: Surgical excision may be a useful treatment option in selected cases
      with solitary, circumscribed liver metastasis from uveal melanoma.

PMID- 9512170
TI  - High-dose intravenous pulse methylprednisolone hemisuccinate in acute Behcet
      retinitis.
AB  - PURPOSE: To report the response of acute Behcet retinitis to high-dose
      corticosteroids. METHOD: Case report. A 58-year-old man with Behcet disease and
      severe bilateral glaucoma experienced a sudden decrease of visual acuity to
      counting fingers in his (better-seeing) left eye. Examination disclosed hypopyon
      uveitis and an infiltrative retinitis threatening the fovea. He received
      intravenous methylprednisolone hemisuccinate, 1 gram per hour on each of 3
      successive days, followed by oral prednisone and cyclosporine. RESULTS: The
      retinal infiltrate disappeared within 24 hours. Visual acuity improved to LE,
      20/400 by day 5 and returned to LE, 20/30 after 3 months. A visual field
      demonstrated a scotoma corresponding to the location of the previous retinitis.
      CONCLUSION: High-dose intravenous methylprednisolone can reverse severe vision
      loss in acute Behcet retinitis.

PMID- 9512171
TI  - Cystoid macular edema associated with cytomegalovirus retinitis in patients with
      the acquired immunodeficiency syndrome.
AB  - PURPOSE: To describe the clinical and fluorescein angiographic appearance of
      cystoid macular edema associated with cytomegalovirus retinitis in patients with
      the acquired immunodeficiency syndrome (AIDS). METHODS: We retrospectively
      examined the clinical and photographic records of four patients with AIDS and
      cytomegalovirus retinitis who developed cystoid macular edema. RESULTS: Seven
      eyes of four patients with AIDS and cytomegalovirus retinitis experienced
      decreased vision associated with cystoid macular edema. Vitreous inflammation was
      mild in each patient. In all eyes, the retinitis involved zone 1, and in all but
      one eye, the cytomegalovirus retinitis was inactive. In one eye, the cystoid
      macular edema was worsened by formation of a dense juxtafoveal epiretinal
      membrane. CONCLUSIONS: Although infrequently recognized, cystoid macular edema
      can cause visual loss in patients with AIDS and cytomegalovirus retinitis.
      Fluorescein angiography should be considered in any patient with cytomegalovirus
      retinitis and unexplained visual loss.

PMID- 9512172
TI  - Topical mitomycin C for the treatment of conjunctival and corneal epithelial
      dysplasia and neoplasia.

PMID- 9512173
TI  - Macular corneal dystrophy in Saudi Arabia: a study of 56 cases and recognition of
      a new immunophenotype.

PMID- 9512174
TI  - Can the choice of antibiotics for therapy of acute otitis media be logical?

PMID- 9512175
TI  - Frequent chronic hepatitis B virus infection in HIV-infected patients positive
      for antibody to hepatitis B core antigen only. Swiss HIV Cohort Study.
AB  - Persons with immune deficiency may present with atypical results in serological
      tests for hepatitis B virus (HBV). Frozen serum specimens that were sequentially
      obtained over time from a cohort of 57 HIV-infected patients, all of whom tested
      positive only for antibody to hepatitis B core antigen (anti-HBcAg), were
      therefore retested for HBV markers, including HBV DNA. The results were assessed
      for their time course and correlated with clinical data and alanine
      aminotransferase (ALT) values. Forty-eight patients were male; intravenous drug
      users constituted the principal risk group (n = 30), followed by homosexual men
      (n = 22). Thirty-three persons tested positive for antibody to hepatitis C virus
      (anti-HCV). During a median of 31 months from the first to the last serum, anti
      HBcAg remained the sole marker of HBV infection in 98.2% of the patients.
      Polymerase chain reaction (PCR) to detect DNA for HBV core and HBV surface gene
      was positive in 126 (62.4%) and 121 (59.9%) of all 202 serum samples,
      respectively. Over time, HBV DNA was detected at least once in 51 (89.5%)
      patients. In contrast, decomplexed hepatitis B surface antigen (HBsAg) was
      detected at least once in 14 (24.6%) patients. Among patients positive for HBV
      DNA and negative for anti-HCV, eight (36.4%) of 22 had chronic hepatitis (ALT
      elevation > or = 6 months) that was attributable only to persisting HBV
      infection. Similarly, 12 (41.4%) of 29 patients positive for both HBV DNA and
      anti-HCV had chronic viral hepatitis, but their ALT values were significantly
      higher. In HIV-infected patients, anti-HBcAg as the sole serological HBV marker
      detected must be considered indicative of chronic HBV infection and is in part
      associated with chronic hepatitis and ALT elevation.

PMID- 9512176
TI  - A new histological procedure for re-evaluation of the serological test for
      Helicobacter pylori.
AB  - To re-evaluate the accuracy of the serological test for Helicobacter pylori,
      fixation of biopsy specimens with Carnoy's solution (preserving the mucous layer
      in tissue preparations) followed by immunohistochemical staining (a new
      histological procedure) was used as the reference histological method instead of
      10% formalin fixation followed by hematoxylin-eosin staining (the conventional
      histological procedure). Biopsy specimens (antrum and body) from 114 patients
      with gastritis (including non-ulcer dyspepsia) or gastric and/or duodenal ulcers
      were obtained by endoscopy and used for both bacteriological culture and
      histological examination. Serum samples were taken from all patients at the time
      of endoscopy. The serum levels of specific IgG and IgA antibodies for
      Helicobacter pylori were measured by commercial enzyme immunoassay kits. The
      reliability of the IgG and IgA measurements was evaluated by analyzing receiver
      operating characteristic curves obtained using the two histological procedures.
      With the conventional histological procedure as the reference, the sensitivity
      and specificity levels of the serological test were 87.2% and 82.1%,
      respectively. With the new histological procedure as reference, sensitivity and
      specificity were 94% and 96.7%, respectively. The insufficient accuracy reported
      for the serological test could be due to false-positive or false-negative results
      obtained when the conventional histological procedure is used as the reference.
      The new histological procedure used here revealed that the serological test for
      Helicobacter pylori is more reliable than previously thought.

PMID- 9512177
TI  - Application of the ATC/DDD methodology to monitor antibiotic drug use.
AB  - In order to monitor the use of antibiotics, it is essential to have comprehensive
      data on drug consumption. The findings of drug utilisation studies can serve to
      describe the pattern of drug use in a particular population, to detect areas of
      concern, and to evaluate the impact of interventions taken to influence the use
      of drugs. In the present study, the Anatomical Therapeutical Chemical
      Classification/Defined Daily Doses (ATC/DDD) system developed by the World Health
      Organisation was evaluated. The system measures the amount of drug used
      independent of package size and sales price, which allows comparisons not only
      within an institution but also within a region, a country, or even
      internationally. Obviously, there can be no modifications of this system. To
      illustrate the method, the pattern of quinolone use in the general population, in
      long-term care facilities, and within a single institution was analysed. These
      drugs were widely used in long-term care facilities in the Nijmegen region of the
      Netherlands, accounting for about 30% of the antibiotics used in these settings,
      whereas in the general population as well as in the University Hospital Nijmegen,
      these drugs constitute only about 6% of the total antibiotics used. These
      differences are large enough to warrant closer analysis of patterns of antibiotic
      usage in different settings to identify the reasons for the use of quinolones and
      to identify measures that might be taken to rationalise the prescription of these
      drugs.

PMID- 9512178
TI  - Emergence of Streptococcus pyogenes strains resistant to erythromycin in
      Gipuzkoa, Spain.
AB  - The aim of this study was to determine the evolution of resistance to macrolides
      and other antibiotics in strains of Streptococcus pyogenes isolated in the
      province of Gipuzkoa, Spain. During the period 1984-1996, all 2561 strains of
      Streptococcus pyogenes studied showed full susceptibility to penicillin. Until
      1990, only 1.2% of Streptococcus pyogenes isolates were resistant to
      erythromycin. Since then, resistance to erythromycin increased every year until
      1995, when 34.8% (87/250) of Streptococcus pyogenes strains were found to be
      resistant. In 1996 the rate of resistance to erythromycin was 17.8% (75/422).
      During the study period, 96.1% (246/256) of the Streptococcus pyogenes isolates
      resistant to erythromycin were susceptible to clindamycin. Of the remaining
      erythromycin-resistant Streptococcus pyogenes strains, resistance to clindamycin
      was constitutive in seven strains and inducible in three. When investigated by
      the polymerase chain reaction (PCR), all Streptococcus pyogenes strains resistant
      to erythromycin and susceptible to clindamycin showed the 1.4 kb fragment of the
      mefA gene, recently described as the novel macrolide-efflux-resistance
      determinant. The most frequent T-agglutination patterns among Streptococcus
      pyogenes resistant to erythromycin were T4 and T8,25. The emergence and rapid
      spread of erythromycin-resistant Streptococcus pyogenes in Gipuzkoa and its
      relationship to the presence of the mefA gene are described.

PMID- 9512179
TI  - Estimation of the avidity of immunoglobulin G for routine diagnosis of chronic
      Toxoplasma gondii infection in pregnant women.
AB  - Present serological methods differentiate poorly between acute and chronic
      toxoplasmosis in pregnant women, particularly when immunoglobulin G (IgG) and
      immunoglobulin M (IgM) antibodies to Toxoplasma gondii are present
      simultaneously. In the present study, a simple test for discriminating between
      high-avidity antibodies, which are usually present in chronic infections, and low
      avidity antibodies, typical of acute infection, was evaluated. Sera were
      evaluated for Toxoplasma gondii antibodies using a commercial enzyme immunoassay,
      but a duplicate well was washed in 6M urea to disrupt low-avidity complexes.
      Results are expressed as the percentage of antibodies resisting elution by urea.
      Equivocal sera (n = 493) containing both IgG and IgM Toxoplasma gondii antibodies
      from 309 pregnant women whose status as chronically or acutely infected had been
      independently determined using standard methods were evaluated for antibody
      avidity. A value of > 35% elution-resistant antibodies was always associated with
      chronic infection and could absolutely exclude a recent (< 3 months) infectious
      incident. Values of < 35% require repeat testing four weeks later to confirm the
      patient's status, since a proportion of individuals with chronic toxoplasmosis
      maintain low-avidity antibodies over long periods. This inexpensive, simple
      method can provide reassurance to clearly chronically infected individuals and
      avoids the need for repeated testing in these cases.

PMID- 9512180
TI  - Acinetobacter baumannii colonization in ventilated preterm infants.
AB  - The role of Acinetobacter baumannii in infections in ventilated preterm infants
      was evaluated in 15 colonized infants (11 male, 4 female) in a pediatric
      intensive care unit. These cases were randomly matched by birth weight and
      gestational age with ventilated non-colonized controls (8 male, 7 female). Case
      records were reviewed for signs and symptoms of infection. Colonized infants were
      ventilated significantly longer (p < 0.05) than controls, and had body
      temperatures of > 37 degrees C for a significantly longer period of time (p <
      0.05). No other parameter of infection differed significantly between the groups.
      The duration of intensive care treatment did not differ between cases and
      controls, nor did the weight gain during intensive care treatment. No fatalities
      occurred in either group.

PMID- 9512181
TI  - Effect of polymorphonuclear neutrophils on serum bactericidal activity against
      Streptococcus pneumoniae after amoxicillin administration.
AB  - The effect of phagocytic killing on serum bactericidal activity against
      Streptococcus pneumoniae was investigated 0, 1.5, 8 and 12 h after a single 875
      mg oral dose of amoxicillin in healthy adults. Killing curves were determined
      with polymorphonuclear neutrophils (PMN), serum or PMN plus serum. Global killing
      (i. e. intracellular and extracellular killing) over 3 h of incubation was
      expressed as the area under the killing curve (AUKC; log cfu x h/ml). Amoxicillin
      did not affect the activity of PMN alone. For serum alone, the AUKC of post
      administration samples (with supra-inhibitory amoxicillin concentrations) was
      significantly lower than in baseline samples. For serum plus PMN, significant
      bactericidal activity of serum was still found in samples after antibiotic
      concentrations had reached sub-inhibitory levels.

PMID- 9512182
TI  - Oxidant-scavenging activities of beta-lactam agents.
AB  - The relative antioxidant effect of ampicillin, ceftazidime, ceftriaxone, and
      cefuroxime on oxygen-reactive species was examined in vitro using stimulated
      human polymorphonuclear neutrophils. There was no evidence that any of the beta
      lactam agents tested had an effect on superoxide or H2O2 generation. In contrast,
      all of the beta-lactam agents prevented hypochlorous acid (HOCI) chlorination of
      1,1-dimethyl-4-chloro-3,5-cyclo-hexanedione in a cell-free system at
      concentrations of < 10 microg/ml. Furthermore, all antibiotics provided dose
      dependent protection against HOCI cytotoxicity to 16HBE140 bronchial epithelial
      cells. Taken together, these data indicate a possible therapeutic role for beta
      lactam agents in protecting host tissues from HOCI-induced oxidative damage.

PMID- 9512183
TI  - Demonstration of Chlamydia trachomatis in Papanicolaou-stained gynecological
      smears.
AB  - A fluorescent antibody staining method was developed to detect Chlamydia
      trachomatis elementary bodies in Papanicolaou-stained cervical smears. Twenty
      five known chlamydia-positive and 12 chlamydia-negative smears were correctly
      identified using this method. Smears from individuals with culture-positive
      chlamydia infections showed a high density of elementary bodies. Among 64 routine
      cervical smears, 27% (6/22) of smears that showed inflammatory changes were
      positive by fluorescent antibody staining for chlamydia, compared to 2.4% (1/42)
      of smears that were negative for inflammatory changes. This method should
      facilitate detection of chlamydia infections in populations undergoing
      cytological screening.

PMID- 9512184
TI  - Use of a microquantity enzyme immunoassay in a large-scale study of measles,
      mumps and rubella immunity in Italy.
AB  - The seroprevalence of antibodies to measles, mumps, and rubella viruses (MMR) was
      determined in 1498 subjects in Catania, Italy, ranging in age from 1 month to 25
      years. The study population was divided into seven age groups and screened by
      enzyme immunoassay using microquantities (10 microl) of whole blood collected by
      fingerprick on filter paper discs. The results showed that seroconversion for
      measles (87.6%) and mumps (73.2%) occurred between 6 and 10 years of age. The
      seroprevalence of antibodies to rubella virus increased slowly through the age
      groups, reaching the highest rate (93.3%) between 16 and 20 years of age.
      Passively transmitted maternal antibodies to mumps and rubella were absent in
      babies between 5 and 8 months of age, and a few cases positive for measles
      antibodies were found among babies 6 and 7 months of age. The enzyme immunoassay
      was demonstrated to be suitable for low-cost large-scale screening for MMR
      immunity. The rate of vaccine failure was also evaluated and found to be 9.5% for
      the measles virus, 12.9% for the mumps virus and 0.0% for the rubella virus.

PMID- 9512185
TI  - Fatal Legionella longbeachae infection following heart transplantation.
AB  - A case of fatal Legionella longbeachae infection following heart transplantation
      is described. Gram stains of respiratory secretions on day 17 posttransplant
      revealed leucocytes and gram-negative bacilli, but there was no growth on routine
      bacterial culture. Legionella longbeachae serogroup 1 was isolated from
      respiratory specimens, blood, and postmortem lung tissue. Legionella longbeachae
      is a common cause of legionellosis in Australia, and infection has been
      associated with exposure to potting mixes. Specific culture for Legionella spp.
      should be performed for any patient who develops pneumonia following organ
      transplantation.

PMID- 9512186
TI  - Thyroid abscess due to Rhodococcus equi in a patient infected with the human
      immunodeficiency virus.
AB  - A case of thyroid abscess due to Rhodococcus equi in an HIV-positive patient with
      previous pulmonary abscess is reported. Rhodococcus equi is a gram-positive rod
      that can cause infections in both immunocompetent and immunocompromised patients,
      though it occurs more frequently in patients with dysfunctional cellular immune
      systems. Several cases of Rhodococcus equi infection in persons infected with HIV
      have been reported. In these patients Rhodococcus equi usually invades the lungs,
      producing pneumonia. These infections often relapse, accompanied by intermittent
      bacteremia, despite conventional treatment. Extrapulmonary abscesses can occur.

PMID- 9512187
TI  - Raynaud's phenomenon and acral necrosis after chemotherapy for AIDS-related
      Kaposi's sarcoma.
AB  - Raynaud's phenomenon is a common vascular side effect of chemotherapy drug
      regimens. Chemotherapy-induced Raynaud's phenomenon leading to acral gangrene has
      rarely been reported. In this report, one patient who developed gangrene after
      bleomycin and vincristine/vinblastine chemotherapy for AIDS-related Kaposi's
      sarcoma and another HIV-infected patient who exhibited symptoms of severe
      Raynaud's phenomenon related to the same regimen are presented. Because the
      combination of bleomycin and vinca alkaloids is commonly used for the treatment
      of AIDS-related Kaposi's sarcoma, clinicians should be aware of the risk of
      provoking acral necrosis in patients who develop Raynaud's phenomenon under
      chemotherapy. The literature is reviewed, and clinical symptoms, pathophysiology,
      and treatment options are discussed.

PMID- 9512188
TI  - Isolation of Staphylococcus caprae from blood cultures of a neonate with
      congenital heart disease.

PMID- 9512189
TI  - Two fatal cases of Veillonella bacteremia.

PMID- 9512190
TI  - First isolation in Europe of Legionella feeleii from two cases of pneumonia.

PMID- 9512191
TI  - Effect of human milk sialyllactose on cytomegalovirus.

PMID- 9512192
TI  - Application and evaluation of a classification system and case definitions of
      Toxoplasma gondii infection.

PMID- 9512193
TI  - Influence of inhaled corticosteroids on growth: a pediatric endocrinologist's
      perspective.
AB  - Given the increasing advocacy for the use of inhaled corticosteroids as a
      treatment of choice for persistent asthma, growing numbers of children are being
      exposed to the possible growth-suppressing effects of glucocorticoids. Recent
      evidence strongly suggests that, when consistently administered at moderate
      doses, inhaled corticosteroids (IC) are capable of slowing growth in children.
      Whether such growth suppression would persist and ultimately affect final adult
      height remains unknown. Therapeutic goals which aim for uninterrupted
      inflammatory disease control rather than periodic symptom control may increase
      the occurrence of growth failure in children treated with IC. In this article,
      current information about the mechanisms of growth suppression by glucocorticoids
      and the effects of IC on growth is reviewed, and recommendations for designing
      studies to investigate the effects of drugs on growth are presented.

PMID- 9512194
TI  - Sexual victimization.

PMID- 9512195
TI  - Technetium-99m-dimercaptosuccinic acid studies and urinary tract infection in
      childhood.

PMID- 9512196
TI  - Neonatal illness severity and new insights into perinatal audit.

PMID- 9512197
TI  - Fatty acid balance studies in term infants fed formula milk containing long-chain
      polyunsaturated fatty acids.
AB  - Long-chain polyunsaturated fatty acids (LCP) are thought to be required for
      optimal nervous system development in the newborn. A commercial milk formula
      containing LCP (Aptamil-LCP) with a fatty acid profile closely resembling breast
      milk, has recently been introduced for term infants. The absorption of fatty
      acids in term infants was examined in a double-blind randomized controlled trial
      comparing Aptamil-LCP (n = 20) and standard Aptamil (n = 20). Formula-fed newborn
      infants were studied from birth for 14 d. Fat balances (3 d) were performed from
      d 10. A 3-d stool collection was performed from d 10 in a parallel breastfed
      group (n = 21). Plasma samples were taken on d 6. Median fat excretion (mg kg[
      1]) was 897.1, 615.0 and 355.2 with Aptamil, Aptamil-LCP and breastfeeding,
      respectively. The median total fat absorption coefficient in Aptamil-LCP-fed
      infants was higher than in those fed standard Aptamil (p < 0.01). These findings
      were accounted for by differences in the excretion and absorption of long-chain
      saturated fatty acids (C14:0, C16:0 and C18:0). Higher fat excretion was
      associated with bulkier and firmer stools. Only trace amounts of LCP were
      detected in the stools of all groups. This accounted for less than 4% of dietary
      intake in Aptamil-LCP-fed infants. No differences in the utilization of LCP from
      Aptamil-LCP and breast milk feeding were apparent. Plasma phospholipid fatty acid
      composition data reflected differences in dietary LCP intake. Thus, PL LCP levels
      were highest in the breastfed infants and lowest in the Aptamil-fed infants, with
      values for the Aptamil-LCP-fed group falling in between.

PMID- 9512198
TI  - Nutrient absorption from a fat-enriched diet in young malnourished children: a
      randomized controlled trial.
AB  - A randomized, controlled trial was undertaken to compare nutrient absorption from
      low fat (22.2% energy as fat) and high fat (48% energy as fat)-containing mixed
      diets in 39 (26M, 13F) malnourished children aged < 2 y. Subjects of both dietary
      groups, standard (SDG, n = 18) and experimental (EDG, n = 21), were offered 184.5
      ml of feeds/kg body weight/24 h that provided 146 kcal with the low fat diet and
      216 kcal with the high fat diet, respectively. The baseline clinical and
      biochemical parameters and the volume of feeds consumed by the patients in the
      two groups were comparable. Thus, the subjects in the EDG were ingesting a mean
      (95% CI) of 50% (23.8%, 76.2%) extra energy than that eaten by the SDG.
      Coefficients of absorption of energy, nitrogen and carbohydrate were similar in
      the two dietary groups (p = 0.08-0.98). Median (binomial exact 95% CI) fat
      absorption among subjects receiving the high fat diet (96.3; 92.9, 98.6) was 7%
      more than in those consuming the low fat diet (89.3; 86.7, 94.1) (p = 0.01).
      Subjects of the EDG thus, retained almost 50% additional energy as compared to
      that by SDG.

PMID- 9512199
TI  - Urinary growth hormone excretion in post-menarcheal adolescent girls with type 1
      diabetes.
AB  - The aim of the present study was to compare measurements of urinary growth
      hormone (GH), serum insulin-like growth factor I (IGF-I) and IGF binding protein
      3 (IGFBP3) between two groups of post-menarcheal girls, 13-18 y of age, one
      comprising 64 type 1 diabetic patients and the other 64 healthy girls matched for
      age and stage of puberty. GH was determined on two occasions in nocturnal urine
      samples by using a modification of an immunoradiometric method for serum.
      Significantly higher urinary GH concentrations but lower IGF-I and IGFBP3 levels
      were found in diabetic girls than in controls (p < 0.001). A significant
      correlation was found between urinary GH concentrations and the daily dose of
      insulin (U kg[-1]) (r = 0.426, p = 0.003). Urinary GH concentrations were also
      significantly related to HbA1c (r = 0.380, p = 0.003). In conclusion,
      disturbances of the GH-IGF-I axis may be evaluated by the use of non-invasive
      urinary GH measurements, which is a simple alternative to frequent sampling of
      serum GH. Increased GH secretion seems to be related to a great need for insulin
      and poor metabolic control. More knowledge about underlying causal factors in the
      disturbed GH-IGF-I axis is required.

PMID- 9512200
TI  - Psychological responses to the needle-free Medi-Jector or the multidose
      Disetronic injection pen in human growth hormone therapy.
AB  - The aim of the study was to test the hypothesis that daily administration of
      growth hormone using the Medi-Jector results in fewer adverse psychological
      responses than needle injection with a multidose injection pen. The Medi-Jector
      is a needle-free injection device that can deliver growth hormone subcutaneously
      through jet injection. The group studied consisted of 18 children aged 10 y or
      over who were participating in a study of the bioequivalence and bioequipotence
      of the administration of growth hormone through jet injection or needle
      injection. Previously, all subjects had received growth hormone therapy with
      commercially available multidose injection pens. The study was designed as a
      prospective, randomized, two-period cross-over trial. A questionnaire was used to
      assess psychological responses such as non-compliance, opinion on ease of
      preparation, affective responses to administration and local side-effects, as
      well as overall preference. In addition, the subjects kept a diary during the
      study. The subjects found the Medi-Jector less offputting (p < 0.01), less
      painful with respect to both frequency (p < 0.04) and intensity (p < 0.01) and
      less unpleasant (p < 0.05) than a multidose injection pen with a 28G needle (p <
      0.01). No difference in compliance was detected. Most subjects preferred the Medi
      Jector for future use (p < 0.05). The mean score on a 1-10 point scale (10 is
      excellent) was 7.9 (SD 1.4) for the Medi-Jector and 6.8 (SD 2.3) for the
      multidose injection pen (p < 0.08). The prevalence of visible bruises each day
      was higher (p < 0.01) with the Medi-Jector (2.5, SD 2.1) than with the multidose
      injection pen (0.7, SD 1.1), but children showed indifferent affective responses
      to bruising. Thirteen out of 18 subjects decided to continue therapy with the
      Medi-Jector (p < 0.06). It is concluded that use of the Medi-Jector in growth
      hormone therapy tends to lead to fewer adverse psychological responses than a
      multidose injection pen with 28G needles.

PMID- 9512201
TI  - Molecular genetics of congenital adrenal hyperplasia (21-hydroxylase deficiency):
      implications for diagnosis, prognosis and treatment.
AB  - The molecular genetics of congenital adrenal hyperplasia due to 21-hydroxylase
      deficiency are reviewed. In Sweden, mutation detection based on allele-specific
      PCR has been used for genetic diagnosis of this disease since 1993. Around 400
      affected 21-hydroxylase genes have been analysed so far. An update of the
      spectrum of mutations among the Swedish patients shows that nine common
      pseudogene-derived mutations are responsible for the disease in around 95% of
      alleles. A total of 13 rare, mostly population-specific mutations have been
      characterized among the remaining 5%. The mutations can be divided into different
      groups according to severity. This makes it possible to predict clinical outcome
      in affected subjects based on genotyping. The risk of salt-wasting and prenatal
      virilization can be estimated, and over-treatment can be avoided in mildly
      affected cases.

PMID- 9512202
TI  - Outcome of children with respiratory symptoms without objective evidence of
      asthma: a two-year, prospective, follow-up study.
AB  - This study evaluated the outcome of 33 children with asthma-like symptoms without
      objective evidence of asthma, and the role of certain factors in predicting the
      development of clinical asthma in these children. Data on symptom histories, lung
      functions (flow-volume spirometry, free running test and methacholine inhalation
      challenge test) and atopic sensitization (skin prick tests and markers of
      eosinophilic inflammation) were collected twice with an interval of 2 y, and the
      diagnoses were re-evaluated after the follow-up period. Based on the results, it
      was concluded that one-third of the children with prolonged or recurrent lower
      airway symptoms, such as cough or wheeze, either have mild asthma or will develop
      asthma in the near future. Children who had a significant response [> or = 10%
      fall in forced expiratory volume in 1 s (FEV1)] in the free running test formed a
      risk group for active asthma, whereas other baseline characteristics seemed not
      to predict the outcome.

PMID- 9512203
TI  - Young female survivors of childhood leukaemia do not have increased somatic
      concerns.
AB  - OBJECTIVE: This study examined whether experience of cancer in childhood leaves a
      hypersensitivity to various somatic symptoms. Further, are self-reported somatic
      symptoms explained by medical late-effects or a worry of recurrence of the
      cancer? METHODS: Of the total of 44 female survivors of leukaemia, 42 were
      compared with 69 age-matched healthy controls. We used a questionnaire to study
      self reported somatic symptoms and a face-to-face interview to explore worries
      about recurrence of the illness. Health status and medical late effects were
      evaluated by a paediatric haematologist. RESULTS: In contrast to our assumptions,
      young survivors of leukaemia reported fewer somatic symptoms than healthy age
      matched comparison subjects (p < 0.001). Late physical sequelae were uncommon
      except in the survivors of allogeneic bone marrow transplantation. Of the
      survivors, 52% were afraid of recurrence of the illness. The presence of physical
      or visible impairment and worry of recurrence were unrelated to frequency of
      somatic symptoms. CONCLUSIONS: The results suggest that experience of childhood
      leukaemia and its treatment does not result in increased somatic concerns or
      hypochondriacal tendencies.

PMID- 9512204
TI  - Distress and the micturating cystourethrogram: does preparation help?
AB  - This study evaluates the impact of therapeutic preparation methods on children
      undergoing MCUG. Parents of 35 children who had undergone MCUG were surveyed by
      questionnaire. The child's reaction to investigation was assessed using the
      Groningen Distress Rating Scale (rating 1 = calm > 5 = panic) and parental coping
      styles using the Utrecht Coping List. Families received one of two types of
      therapeutic preparation: storybooklet or storybooklet and play preparation.
      Reported distress levels were significantly lower with therapeutic preparation
      (mean score 2.5 +/- 1.02 SD) than without (mean score 3.3 +/- 1.22 SD).
      Previously, controls reported 46% of anxiety-linked behaviour changes post-MCUG,
      falling to 13% after therapeutic preparation. Parents who gave a candid
      explanation reported significantly lower child distress levels (mean 2.0 +/- 0.91
      SD) than those parents who avoided upsetting details (mean 3.1 +/- 0.47 SD). We
      conclude that distress associated with the MCUG can be reduced by therapeutic
      preparation of the child and family prior to investigation.

PMID- 9512205
TI  - Placental transfer favours high avidity IgG antibodies.
AB  - The aim of the present study was to evaluate if maternal-foetal antibody
      placental transfer may be affected by antibody avidity. We compared the avidity
      index (AI) of IgG antibodies to tetanus toxoid (TT) and to type 3 pneumococcal
      antigen (Pn) in cord blood of 10 healthy term and 8 preterm infants and in their
      mothers' sera at delivery. In order to evaluate whether a heavier antigenic
      exposure may influence the placental transfer, we also studied 15 Pakistani
      maternal sera and cord blood pairs. TT- and Pn-specific antibody AI was
      significantly higher in Italian and Pakistani term infants than in their mothers,
      while a significant difference in specific TT antibody AI, but not in specific Pn
      antibody AI was observed between preterm infants and their mothers. Italian and
      Pakistani cord blood/maternal serum pairs showed comparable values of AI. Our
      data suggest that high avidity antibodies preferentially cross the placenta; this
      seems to start early during gestation and appears to be related to the nature of
      the antigen to which the antibodies are directed, but not to the degree of
      antigenic exposure.

PMID- 9512206
TI  - Thyroid hormone concentrations in preterm infants born to pre-eclamptic women
      with placental insufficiency.
AB  - The aim of this study was to compare thyroid function in preterm infants born to
      women with placental insufficiency (n = 15) and those born to women without
      placental insufficiency (n = 13). Gestational ages ranged between 28 and 33
      weeks. Concentrations of free thyroxine (FT4), thyrotropin (TSH),
      triiodothyronine (T3) and reverse T3 (rT3) were measured by radioimmmunoassays in
      cord blood and on d 1, 3, 5, 7, 14 and 21. Infants born to the women with
      placental insufficiency had significantly lower mean FT4 (p = 0.001), TSH (p =
      0.002) and rT3 values (p = 0.025) in cord blood, and higher rT3 values on d 5 (p
      = 0.019) and d 7 (p = 0.025). The following conclusions were reached: (i) preterm
      infants born to pre-eclamptic women with placental insufficiency have intact
      hypothalamic-pituitary-thyroid axes; (ii) compared to preterm infants born to
      healthy women, preterm infants born to pre-eclamptic women with placental
      insufficiency have lower FT4 and TSH concentrations before birth and (iii)
      elevated rT3 concentrations after birth, suggesting a temporarily impaired
      hepatic type 1 deiodination process.

PMID- 9512207
TI  - Randomized, controlled, blinded trial of doxapram for extubation of the very low
      birthweight infant.
AB  - The objective of the study was to determine whether administering doxapram by
      infusion to the very low birthweight infant, prior to extubation during the first
      3 weeks of life, would increase the incidence of successful extubation. The study
      patients, 56 infants of less than 1251 g birthweight and less than 30 weeks'
      gestation, were entered in the first 3 weeks of life when lung disease had
      started to improve. A randomized blinded trial was performed, with infants
      receiving 3.5 mg kg(-1) doxapram bolus, followed by an infusion at 1 mg kg(-1) h(
      1), or placebo. Weaning from positive pressure ventilation was standardized and
      extubation occurred after a 12 h trial of an intermittent mandatory ventilation
      (IMV) rate of 6 breaths min(-1), if PCO2 < 55 mmHg, pH > 7.26, and FiO2 < 0.45.
      Study drug was continued for 48 h postextubation, and the infants were placed on
      nasopharyngeal continuous positive airway pressure (CPAP) for 72 h
      postextubation. Extubation failure within the first 72 h after extubation was
      objectively defined in terms of acidosis (pH < 7.26), hypercarbia (PCO2 > 55
      mmHg), excessive oxygen requirement (FiO2 > 0.8) or frequent apnoea (more than
      three in 12 h, or more than two requiring face mask IMV in 24 h). No difference
      was noted in the frequency of successful extubation between the groups. Fifteen
      infants in each group were successfully extubated before the 10th day of the
      study. In conclusion, when given in accordance with this protocol doxapram does
      not increase the likelihood of successful extubation in the very low birthweight
      infant. Increasing successful extubations in this group of infants will require
      other strategies.

PMID- 9512208
TI  - The use of CRIB (clinical risk index for babies) score in auditing the
      performance of one neonatal intensive care unit.
AB  - The CRIB (clinical risk index of babies) score was developed to overcome the
      disadvantages of birthweight-specific comparisons between neonatal units. The
      aims of this study were to assess the ability of CRIB score compared to
      birthweight and gestational age to predict hospital mortality in very low
      birthweight infants and to use CRIB score in auditing one unit's performance
      during a prolonged time period. The charts of 335 infants with birthweight < or =
      1500 g born between 1980 and 1995 were reviewed retrospectively. CRIB predicted
      hospital mortality significantly better than birthweight and gestation and
      performed equally well, whether the infants were treated with synthetic
      surfactant or not. When adjusting for CRIB score there was a significant
      improvement in the unit's performance, probably owing to the introduction of
      surfactant. As small samples tend to be associated with wide confidence
      intervals, use of CRIB is recommended in comparing risk adjusted mortality in a
      single unit over several years, as in this study, or between large groups of
      neonatal units over shorter periods.

PMID- 9512209
TI  - Anxiety and depression in mothers related to severe malformation of the heart of
      the child and foetus.
AB  - The aim of the study was to assess levels of anxiety and depression in three
      groups: pregnant mothers referred to foetal cardiology, subdivided into those
      with a confirmed diagnosis and those for which no abnormality was detected, and
      mothers who had a child with a heart malformation. Psychological status was
      measured between 6 and 10 months after diagnosis using the Hospital Anxiety and
      Depression scale in 108 females. Levels of anxiety were higher in the two groups
      with a confirmed diagnosis in the antenatal period or after birth (62%) than in
      those who were screened positively but in whom no abnormality was found (30%) (p
      = 0.0055). Anxiety was the highest in young females who had a foetus with a heart
      malformation. Depression scores were higher in those who had a child with heart
      malformation (18%) than in the other two groups (5%). Mothers who terminated a
      pregnancy after diagnosis remained depressed long after the event. Younger
      mothers may be especially vulnerable to mood problems associated with a traumatic
      obstetric experience.

PMID- 9512210
TI  - Injuries to pre-school children in a home setting: patterns and related products.
AB  - The current study was undertaken to examine the most typical circumstances of and
      products related to injuries to pre-school children at home, and to establish the
      extent to which any injury patterns found were age- or gender-related. Data were
      taken from a community-based injury register built up over a 1-y period in a
      Swedish county. Injury incidence by gender and age was calculated, and typical
      injury patterns were identified through analysis of seven characteristics of the
      injuries, employing multivariate techniques. Injury incidence was higher for
      children aged 1 and 2 y, and for boys at all pre-school ages. Five typical injury
      patterns were identified, and their relation to gender and age highlighted. It is
      concluded that a focus on passive protection is likely to offer the most
      effective means of prevention. This could be achieved by safer home designs,
      building structures, items of equipment and products.

PMID- 9512211
TI  - Sexual victimization in adolescent girls (age 15-20 years) enrolled in post
      mandatory schools or professional training programmes in Switzerland.
AB  - An analysis of data from the Swiss Multicenter Adolescent Survey on Health was
      conducted to assess the prevalence of a history of sexual victimization among a
      national sample of adolescent girls enrolled in schools or professional training,
      to estimate the number of associated psychosocial health problems, and to gain
      information on the effects of disclosure of the experience. A representative
      sample of 9268 adolescents answered a written questionnaire on health and
      lifestyle. Of the 3993 participating girls, 18.6% reported an experience of
      sexual victimization. The burden of associated psychosocial health problems was
      considerable, notably as regards depression, suicidal behaviour and substance
      misuse. Preliminary findings on the relation of disclosure and mechanisms of
      learned helplessness stress the need for more research on this issue. The results
      stress the importance of prevention programmes for adolescents and
      preadolescents, of physicians' awareness and training for screening and
      appropriate counselling, and of easy access to professional support.

PMID- 9512212
TI  - Drug prescribing for children in general practice. A report from the More &
      Romsdal Prescription Study.
AB  - To investigate general practitioners' drug prescribing patterns for children (0
      12 y), an observational, cross-sectional study was conducted in Western Norway.
      Seven thousand, two hundred and twenty-nine GP-patient contacts during which 5222
      drugs were prescribed, were included for analysis. The highest prescribing rates
      were for boys < 2 y (82.1 prescriptions per 100 contacts). Two-thirds of all
      prescriptions were for drugs in main groups respiratory system or systemic anti
      infectives. The 20 most commonly prescribed agents comprised 75% of all
      prescriptions. The 20 most frequently recorded diagnoses for prescribing
      comprised 81% of all. Phenoxymethylpenicillin was the most frequently prescribed
      antibiotic for otitis, tonsillitis and sinusitis, while erythromycin was used
      most often for bronchitis and pneumonia. Antibiotics were prescribed in more than
      8/10 contacts for tonsillitis, sinusitis, acute bronchitis and pneumonia, and in
      two-thirds of all contacts for urinary tract infections. Sixty-five percent of
      the antibiotic prescriptions for urinary tract infections were for co
      trimoxazole.

PMID- 9512213
TI  - Neonatal flumazenil therapy reverses maternal diazepam.
AB  - A woman at 32 weeks' gestation with eclampsia was given 120 mg diazepam shortly
      before emergency caesarean section. The infant had persistent apnoea and required
      respiratory support. Spontaneous respiration began after intravenous flumazenil
      infusion was started. Diazepam and its active metabolites were assayed during and
      after 5 d of treatment with flumazenil.

PMID- 9512214
TI  - Lethal ornithine transcarbamylase deficiency in a female neonate: a new case.

PMID- 9512215
TI  - Intractable diaper dermatitis as an early sign of biotin deficiency.

PMID- 9512216
TI  - Color Doppler ultrasonography for evaluation of gastroesophageal reflux in a sick
      child.

PMID- 9512217
TI  - Embryo research in the US.

PMID- 9512218
TI  - Treatment of hyperinsulinaemia in polycystic ovary syndrome?

PMID- 9512219
TI  - Beyond providing information: the Internet as a research tool in reproductive
      medicine.

PMID- 9512220
TI  - The origin of serum progesterone during the follicular phase of menotropin
      stimulated cycles.
AB  - The study was designed to investigate the source of progesterone secretion during
      pituitary suppression and ovarian stimulation. It involved 416 women undergoing
      in-vitro fertilization (IVF) who were treated with gonadotrophin-releasing
      hormone agonist (GnRHa) and human menopausal gonadotrophin (HMG) (group I), 139
      women undergoing ovulation induction with HMG only (group II) and nine women who
      were diagnosed previously as late-onset adrenal hyperplasia and treated
      continuously with dexamethasone, in addition to ovulation induction (group III).
      During HMG treatment, serum oestradiol and progesterone were measured every 1-2
      days. If progesterone concentration exceeded 3.0 nmol/l, at least 36 h before
      human chorionic gonadotrophin (HCG) administration, the patients were
      prospectively randomized to treatment with dexamethasone or not and the hormones
      concentrations were measured again 12 h later. Mean age and pretreatment serum
      concentrations of dehydroepiandrosterone sulphate, androstenedione, testosterone
      and luteinizing hormone/follicle stimulating hormone (LH/FSH) ratio, were not
      significantly different in the patients with and without progesterone elevation.
      Pituitary down-regulation did not reduce the incidence of progesterone elevation
      (13.9 and 12.2% in groups I and II respectively), while in group III,
      progesterone concentrations did not increase. After dexamethasone administration
      a significant decrease in serum progesterone concentration was demonstrated (mean
      +/- SD, -2.1 +/- 1.4 and -1.6 +/- 1.2 in groups I and II respectively, while in
      the untreated patients it increased (+1.9 +/- 1.9 and +4.2 +/- 4.8). The increase
      in serum progesterone concentrations was not accompanied by an increase in
      cortisol and 11-deoxycortisol but by an increase in LH. After dexamethasone
      administration the concentrations of cortisol, 11-deoxycortisol and LH
      significantly decreased. Progesterone concentration was positively correlated
      with both oestradiol concentration (r = 0.290; P < 0.05) and the number of
      oocytes retrieved (r = 0.207; P < 0.05). We conclude that at least a part of
      serum follicular-phase progesterone appears to be of adrenal origin. High
      oestrogen concentrations (or other ovarian factors) may cause changes in the
      hypothalamic-pituitary-adrenal axis and in adrenal enzyme activity as a part of
      the complex 'cross-talk' between the hypothalamic-pituitary-ovarian and the
      hypothalamic-pituitary-adrenal axes.

PMID- 9512221
TI  - Detecting pre-ovulatory luteinizing hormone surges in urine.
AB  - The study objectives were to determine (i) if pre-ovulatory luteinizing hormone
      (LH) surges, undetected in urine by two immunoradiometric assays (IRMA), were
      detectable by an ultrasensitive immunofluorometric assay (IFMA) and (ii) the
      influence of creatinine adjustment on the detection and timing of the urinary LH
      surges. Daily urine specimens were contributed by healthy 25-36 year old
      volunteers during 14 ovulatory menstrual cycles for an epidemiological study
      conducted in 1983-1985. Specimens were selected as having been previously assayed
      by two IRMA without consistently detecting LH surges. These urine specimens were
      remeasured using an IFMA and adjusted for creatinine concentration. IFMA
      measurements revealed unambiguous LH surges in all cycles. Adjusting IRMA urinary
      LH values for creatinine concentrations revealed previously undetected LH surges
      in four of eight cycles. Creatinine adjustment also altered the timing of IRMA
      and IFMA LH surges by 1-5 days. These results demonstrate an IFMA that detects
      pre-ovulatory LH surges in unpreserved, frozen urine from cycles where such
      surges were previously undetectable. Further, creatinine adjustment can markedly
      affect detection and timing of the onset and peak of the urinary LH surge. While
      our analysis suggests that this adjustment improves the validity of the LH
      measure, this requires further investigation.

PMID- 9512222
TI  - Effect of gonadotrophin-releasing hormone agonist treatment on growth hormone
      secretion in women with polycystic ovarian syndrome.
AB  - The suppression of the pituitary-gonadal axis by the administration of
      gonadotrophin-releasing hormone agonists (GnRH-a) is used occasionally as an
      adjunct therapy with gonadotrophins for ovulation induction in women with
      polycystic ovarian syndrome (PCOS). A number of recent clinical studies have
      suggested that women with polycystic ovaries (PCO) may have disturbances of
      normal growth hormone (GH) kinetics and alterations in the GH/insulin-like growth
      factor (IGF)-I system. The purpose of this study was to determine the effect of
      GnRH-a administration on GH-releasing hormone (GHRH)-stimulated GH release in
      women with PCOS. Eight women with PCO and six control women were studied before
      and after 2 months of treatment with the long acting GnRH-a triptoreline (3.75 mg
      monthly injections). GHRH was given as a single i.v. injection and blood samples
      for GH measurements were obtained at -15, 0, 30, 60, 90 and 120 min. The GH
      responses were expressed as the area under the curve (AUC) or the differences
      from the basal value (delta(max)). The GH response to GHRH (mean +/- SEM) was
      lower in women with PCO (AUC 114.9 +/- 43.1 versus 206.2 +/- 28.7 ng/ml/120 min,
      P < 0.05 and delta(max) 31.6 +/- 8.2 versus 49.4 +/- 5.8 ng/ml, P < 0.05). After
      treatment with the GnRH-a, the GH response to GHRH was significantly smaller than
      before treatment in both groups (PCO AUC 34.6 +/- 9.0 ng/ml/120 min and
      delta(max) 12.4 +/- 3.1 ng/ml; controls AUC 148.8 +/- 28.4 ng/ml/120 min and
      delta(max) 31.2 +/- 6.1 ng/ml), but the PCO group had a significantly smaller
      response. These data demonstrate that women with PCO have a reduced GH response
      to GHRH compared with normal controls and that GnRH-a administration causes a
      further GH reduction in both groups. Women with PCO have a greater suppression of
      GH response to GHRH during treatment with GnRH-a. This suggests that a different
      level of sensitivity in the somatotrophic axis exists in PCOS.

PMID- 9512223
TI  - Cortisol concentrations in follicular fluid of 'low responder' patients.
AB  - The study was undertaken to examine any differences existing in total cortisol
      concentrations in the follicular fluid (FF) of pre-ruptured follicles between
      'low responder' patients (group 1, n = 20) and 'good responder' patients (group
      2, n = 15). The groups were defined according to how many oocytes had been
      retrieved during the previous in-vitro fertilization procedure (group 1: three or
      fewer; group 2: more than three) and total oestradiol concentration at previous
      in-vitro fertilization (IVF) (group 1: < or = 500 pg/ml; group 2: > 500 pg/ml).
      All patients were aged 36-43 years (group 1 mean +/- SD: 38.2 +/- 4.7; group 2:
      32.1 +/- 3.8 years) and were diagnosed with tubal or unexplained infertility. The
      total FF cortisol concentrations obtained in conjunction with an IVF procedure
      were assayed and related to oocyte fertilization. Follicular fluid was analysed
      for total cortisol content. Only follicles between 19 and 20 mm diameter were
      analysed in both groups. After aspiration of blood-free FF, total cortisol
      concentrations were measured by radioimmunoassay, designed for the quantitative
      measurement of cortisol, and related to oocyte fertilization. Total cortisol
      concentration in FF from fertilized oocytes was 9.7 +/- 0.6 microg/ml (mean +/-
      SD) in group 1 compared to 9.2 +/- 4.4 microg/ml in group 2 (not statistically
      significant). Total cortisol concentrations were not associated with oocyte
      fertilization and no difference between the groups was found in total cortisol
      concentrations in the FF of unfertilized oocytes or empty follicles.

PMID- 9512224
TI  - Serum concentration of vascular endothelial growth factor cannot predict the
      course of severe ovarian hyperstimulation syndrome.
AB  - Vascular endothelial growth factor (VEGF) is stated to be a possible promoter of
      the development and the severity of ovarian hyperstimulation syndrome (OHSS). The
      secretion of VEGF in granulosa cells seems to be human chorionic gonadotrophin
      (HCG) dependent. In this prospective study, the data of 10 patients suffering
      from severe OHSS with ascites and pleural effusions (haematocrit, fluid balance,
      serum HCG, serum oestradiol) were analysed. The serum VEGF concentration declined
      during the period of clinical improvement but provided no additional diagnostic
      information for the further course of OHSS. VEGF was neither an early marker of
      improvement, nor of worsening of the clinical picture of the OHSS. Serum
      oestradiol concentrations and serum VEGF concentrations showed a statistical
      correlation (r = 0.33, P < 0.001). There was no correlation between haematocrit
      and VEGF, nor between serum HCG and VEGF. To conclude, although VEGF may be
      involved in the pathogenesis of OHSS, it is not an important clinical marker for
      the course of an OHSS.

PMID- 9512225
TI  - Human leukocyte antigen matching and fetal loss: results of a 10 year prospective
      study.
AB  - The role that maternal and fetal human leukocyte antigen (HLA) genes play in
      pregnancy is unknown, but it has been suggested that fetuses whose HLA alleles do
      not differ from maternal alleles (i.e. histocompatible fetuses) are more likely
      to be aborted than fetuses with HLA alleles that differ from maternal alleles
      (i.e. histoincompatible fetuses). To elucidate the role of HLA compatibility in
      pregnancy, we tested the hypothesis that couples who match for HLA alleles or
      haplotypes would have reduced fertility because only these couples could produce
      histocompatible fetuses. We conducted a 10 year prospective study of HLA matching
      and pregnancy outcome in 111 Hutterite couples, providing information on 251
      pregnancies. A logistic regression analysis was performed to determine the
      effects of HLA matching at HLA regions and loci on pregnancy outcome (fetal loss
      versus delivery). Significantly increased fetal loss rates were observed among
      couples matching for the entire 16-locus haplotype (P = 0.002). Among the
      individual loci, loss rates were increased among couples matching for HLA-B (P =
      0.019), HLA-C (P = 0.033) and the complement component, C4 (P = 0.043). We
      interpret these results as evidence that matching for the entire 16-locus
      haplotype and/or alleles at an HLA-B-linked locus confers significant risk for
      fetal loss.

PMID- 9512226
TI  - Characterization of endometrial T lymphocyte subpopulations in spontaneous early
      pregnancy loss.
AB  - T lymphocyte subpopulations were compared in normal first trimester human decidua
      and in decidua associated with spontaneous abortion. Cryostat sections were
      labelled using a panel of monoclonal antibodies specific for CD3, CD8, CD4 and
      for the alphabeta and gammadelta heterodimers of the T cell receptor using an
      avidin-biotin complex peroxidase method. All the endometrial T cell subsets which
      have been demonstrated in normal early pregnancy were detected in similar numbers
      and proportions in spontaneous abortion. The findings suggest that adverse
      pregnancy outcome is not influenced by altered proportions of T cell
      subpopulations; nevertheless, the possibility remains that these cells may have
      an altered antigenic phenotype in spontaneous abortion which could contribute to
      pregnancy success or failure.

PMID- 9512227
TI  - Increased frequency of congenital chromosomal aberrations in female partners of
      couples undergoing intracytoplasmic sperm injection.
AB  - We evaluated the frequency of congenital chromosomal aberrations in a sample of
      305 couples included in an intracytoplasmic sperm injection (ICSI) programme.
      Twenty individuals (3.3%) with congenital chromosomal abnormalities could be
      identified. The following types of abnormalities were observed: reciprocal
      translocations (n = 7), Robertsonian translocations (n = 3), inversions (n = 3),
      other structural aberrations (n = 4) and sex chromosome aberrations (n = 3). The
      rate of chromosomally abnormal males (10/305, 3.3%) lay within the expected range
      for patients with reduced semen quality. Surprisingly, 50% (10/20) of all
      abnormal karyotypes were contributed by the female partner of ICSI patients.
      These data confirm the higher incidence of chromosomal aberrations in infertile
      populations as compared with the baseline population risk. Additionally, the data
      imply that in some cases of male factor infertility a hidden female chromosomal
      factor may be present, which cannot be identified by standard clinical
      evaluation. In conclusion, we recommend chromosomal analysis in both partners of
      couples undergoing ICSI treatment.

PMID- 9512228
TI  - Post-pubescent to mature fathers: increase in progeny quality?
AB  - In the mouse, offspring born from mature fathers exhibit better behavioural
      performances (for spontaneous activity in both sex and learning capacity in
      males) than those born from post-pubescent fathers. These behavioural variations
      are not accompanied by other obvious modifications. They could correspond to what
      has been observed in man relating to the results in a psychometric test undergone
      by male progeny born from very young to mature fathers. These data and those
      which show a decrease in mental performance in rats and human males born from
      mature to senescent fathers suggest the participation of some genetic factors in
      these phenomena.

PMID- 9512229
TI  - Sperm chromosome analysis in the father of a child with a de-novo reciprocal
      translocation t(11;15)(q12;q22) by G-banding and fluorescence in-situ
      hybridization.
AB  - Analysis of sperm chromosomes by G-banding and two-colour fluorescence in-situ
      hybridization (FISH) was carried out in the father of a child with a de-novo
      reciprocal translocation t(11;15)(q12;q22). Sperm chromosome complements were
      obtained after in-vitro fusion of zona-free hamster oocytes and donor
      spermatozoa. A total of 112 sperm complements was first analysed by G-banding.
      The frequency of structural chromosome aberrations (9.8%) and the conservative
      frequency of aneuploidy (0.0%) were not significantly different from those
      obtained in our control donors. The proportions of X-bearing (53.2%) and Y
      bearing (46.8%) spermatozoa were not significantly different from the expected
      1:1 ratio. A total of 313 sperm complements was analysed by two-colour FISH. The
      frequency of structural abnormalities for chromosomes 11 and 15 was 3.2 and 0.3%
      respectively. The frequency of rearrangements for chromosome 11 was statistically
      significant when compared with control donors (0.4%) (P < 0.0001). No spermatozoa
      with the t(11;15)(q12;q22) translocation were observed, showing no evidence for a
      germ-cell mosaicism. These results suggest that the de-novo involvement of
      chromosome 11 in a structural rearrangement is not random, and that in this
      patient an increased risk of de-novo structural chromosome abnormalities in
      further offspring does exist.

PMID- 9512230
TI  - Low pregnancy rate is achieved in patients treated with intracytoplasmic sperm
      injection due to previous low or failed fertilization in in-vitro fertilization.
AB  - The main indications for intracytoplasmic sperm injection (ICSI) are severe male
      factor and fertilization failure or a low fertilization rate in previous in-vitro
      fertilization (IVF) treatments. The fertilization and pregnancy rates after ICSI,
      however, are seldom reported separately for these two different indications. The
      aim of this study was to compare the treatment outcome and pregnancy rate after
      ICSI between 65 patients with previous failed fertilization or a low
      fertilization rate without male factor, and 219 patients with a primary male
      factor. From the 2726 oocytes collected, 2087 (77%) were micro-injected and 1355
      (65%) achieved normal fertilization. The oocyte fertilization rate was similar in
      the group with previous failed fertilization or a low fertilization rate and the
      group with a male factor (65 and 65% respectively), as was the cleavage rate of
      normally fertilized oocytes (92 and 94% respectively). Despite the similar
      fertilization and cleavage rates and the similar number and morphological quality
      of embryos transferred in both groups, the pregnancy rate was significantly lower
      (P < 0.05) in the group with previous failed fertilization or a low fertilization
      rate than in the group with a male factor (19.6 versus 33.5% respectively; 95%
      confidence intervals for the difference, 2-26%). The implantation rate was also
      lower (P = 0.01) in patients with previous failed fertilization or a low
      fertilization rate (9.6%) than in the group with a male factor (19.5%). We
      conclude that patients with previous failed fertilization or a low fertilization
      rate in standard IVF without male factor have a significantly smaller chance of
      becoming pregnant after subsequent ICSI than patients with a primary male factor.
      This poor outcome probably reflects intrinsic oocyte defects not bypassed by
      ICSI.

PMID- 9512231
TI  - Falloposcopic tuboplasty for bilateral tubal occlusion. A novel infertility
      treatment as an alternative for in-vitro fertilization?
AB  - The linear everting (LE) catheter has been developed to safely guide a
      Falloposcope into the entire length of Fallopian tube in order to observe the
      tubal lumen. It may also be useful therapeutically for the recanalization of
      occluded tubes. Fifty infertility patients who had been diagnosed with proximal,
      mid and distal tubal occlusion by hysterosalpingogram, Rubin test and
      hysteroscopic selective hydrotubation, were selected to undergo Falloposcopic
      tuboplasty (FT). Patients having hydrosalpinges were excluded from the study
      group. The total number of tubes treated was 102 during 53 FT procedures. On the
      basis of tubes attempted, the LE catheter successfully accessed 85.3% (87/102). A
      follow-up hysterosalpingogram was completed 1-3 months following the FT
      procedure, which revealed an overall patency rate of 79.4% (81/102). During FT, a
      high incidence of multiple adhesions was observed in the entire length of tubal
      lumen in patients having bilateral occlusions. To date, the total number of
      pregnancies following FT treatment is 11 over a follow-up period of 2 months to 3
      years. FT has been established as a highly useful, less invasive and novel
      treatment for tubal infertility. This technique may be useful in selected
      patients with tubal infertility.

PMID- 9512232
TI  - Hysterosalpingography with a balloon catheter versus a metal cannula: a
      prospective, randomized, blinded comparative study.
AB  - A prospective, randomized, blinded study was conducted to compare the use of a
      balloon catheter for performing hysterosalpingography (HSG) with the use of a
      traditional metal cannula. Sixty-one consecutive women who underwent HSG for
      evaluation of infertility were prospectively randomized to undergo the procedure
      with either a metal cannula (n = 31) or the balloon catheter (n = 30). The HSG
      procedure was identical in both groups. HSG using the balloon catheter, compared
      to the metal cannula, required significantly less fluoroscopic time (57.4 +/-
      17.6 versus 75.6 +/- 40.5 s), smaller amounts of contrast medium (7.8 +/- 3.9
      versus 20.1 +/- 15.8 ml), produced less pain (3.8 +/- 2.0 versus 5.6 +/- 2; on a
      scale of 1-10), and was easier for the physician to perform (8.8 +/- 1.1 versus
      6.4 +/- 1.9; on a scale of 1-10) (P < 0.01). Eight patients (13%) were diagnosed
      as having proximal tubal occlusion. It was possible to offer an immediate
      transcervical tubal catheterization for further diagnosis and treatment of the
      occlusion only to the five patients with this condition from the balloon catheter
      group. We conclude that the balloon catheter is superior to the traditional metal
      cannula for performing HSG. Furthermore, if proximal tubal occlusion is
      diagnosed, an immediate selective salpingography and transcervical tubal
      catheterization can be performed without the need to replace the cannula or to
      reschedule the patient.

PMID- 9512233
TI  - Modelling of the probability of success of the stages of in-vitro fertilization
      and embryo transfer: stimulation, fertilization and implantation.
AB  - The aim of this study was to find the factors explaining the probability of
      success of in-vitro fertilization (IVF)-embryo transfer and its different stages:
      stimulation, fertilization and implantation. The sample came from a retrospective
      cohort followed in the IVF-embryo transfer centre of the Centre Hospitalier
      Universitaire of Pellegrin, Bordeaux, France; the data from 471 couples giving
      rise to 923 IVF-embryo transfer cycles were recorded. Four logistic regression
      models were specified for global process, stimulation, fertilization and
      implantation stages. Random effect models were used for taking into account the
      correlations of the different cycles for the same woman. The main outcome
      measures were: ongoing pregnancy, number of oocytes, number of embryos. A total
      of 135 ongoing pregnancies was observed. The significant explanatory variables
      were for global process: age [> or = 38 years: odds ratio (OR) = 0.28], donor
      sperm IVF-embryo transfer (OR = 2.1), number of ampoules (OR = 0.98), previous
      IVF-embryo transfer livebirth (OR = 2.36); for stimulation: age (> or = 35 years:
      OR = 0.38) and number of days of treatment > 13 days (OR = 0.20); for
      fertilization: accident during previous IVF-embryo transfer gestation (OR =
      0.39), absolute tubal infertility (OR = 1.38) and the number of ampoules of human
      menopausal gonadotrophin (HMG) per day (OR = 0.85); for implantation: age (age >
      or = 38 years: OR = 0.34), donor sperm IVF-embryo transfer (OR = 4.58), number of
      ampoules (OR = 0.98), number and quality of the embryos. Estimates of the
      probabilities of success are also given for the global process.

PMID- 9512234
TI  - Failure to collect oocytes in assisted reproductive technology: a retrospective.
AB  - While there is much information and discussion on pregnancy failure after
      assisted reproductive technologies, less emphasis is placed on the failure to
      collect oocytes after apparently successful ovarian stimulation. This
      retrospective survey reviewed 4973 treatment cycles in order to obtain
      information about the likelihood of this event. Overall 42 women (43 treatment
      cycles) failed to have oocytes collected [0.86% of treatments started and 0.92%
      of women given human chorionic gonadotrophin (HCG)]. However, in only six cases
      was this failure unexpected (0.1%) with no obvious potential clinical reason
      (i.e. all six cases had: HCG administered; more than two follicles >15 mm in
      diameter; oestradiol values >2000 pmol/l; <38 years old; normal body mass index).
      Indifference concerning uncommon events is fraught with peril, as although rare,
      the particular outcome may be devastating to the individual, both economically
      and psychologically. Eighteen of the 42 women did not return for on-going
      treatment suggesting increased contact by clinic staff may be required when
      oocyte retrieval is not achieved. These data suggest that the failure to collect
      oocytes after apparently successful ovarian stimulation is rare and random. The
      information has proved useful in allaying the fears of couples contemplating
      assisted reproductive technologies.

PMID- 9512235
TI  - Cost-effectiveness analysis of in-vitro fertilization: estimated costs per
      successful pregnancy after transfer of one or two embryos.
AB  - Standard protocols for in-vitro fertilization (IVF) include transfer of two or
      three embryos. Not surprisingly, the rate of twin pregnancy after IVF is high
      (about 24% of all pregnancies). Routine transfer of one, rather than two, embryos
      would be expected to result in a much lower rate of twin pregnancies at the cost
      of a lower take-home baby rate. The aim of this study was to compare hypothetical
      costs to society incurred by pregnancies achieved with IVF protocols based on the
      transfer of one or two embryos. We compared actual (for two-embryo transfers) and
      hypothetical (for one-embryo transfers) take-home baby rates; risks of twin
      pregnancies; and costs of sick leave and hospitalization during pregnancy,
      deliveries, neonatal intensive care, and handicap care after transfer of one or
      two embryos. The study showed that even when more treatments might be needed to
      achieve similar baby take-home rates after transfer of one compared with two
      embryos, the lower twin pregnancy rate of the former approach caused it to be
      more cost-efficient than the latter. In conclusion, IVF costs are the sum of
      fertilization treatment costs and the costs for health care of the pregnant women
      and their offspring. Considering the association of the latter costs with numbers
      of embryos transferred, studies of one-embryo transfer protocols are urgently
      needed.

PMID- 9512236
TI  - Dizygotic twinning as a measure of human fertility.
AB  - There is widespread concern about a possible decline in human fertility in recent
      decades. The spontaneous dizygotic twinning rate provides a way of measuring a
      combination of male plus female fertility as it reflects the frequency of double
      ovulation, the probability of fertilization, and the survival of the zygote.
      There was a decline in dizygotic twinning rates in developed countries which
      began around 1960 and continued until the late 1970s. The exact cause of the fall
      remains unknown. We suggest that it could have been due to a depression in the
      twin ovulation rate in women who stopped taking the oral contraceptive pill. The
      rise in the dizygotic twinning rates which occurred from the 1980s onwards in
      developed countries is almost certainly due to increasing use of ovulation
      inducing agents, but this rise may have masked a continuing decline in dizygotic
      twinning. Monozygotic twinning rates have remained remarkably constant or
      increased only very slightly in recent decades. This makes it possible to use the
      dizygotic:monozygotic twinning ratio to monitor dizygotic twinning in populations
      where true incidence rates cannot be calculated, e.g. in hospitals where there
      may be selective referral of twins.

PMID- 9512237
TI  - Transvaginal hydrolaparoscopy as an outpatient procedure for infertility
      investigation.
AB  - A new technique called transvaginal hydrolaparoscopy is described for the
      exploration of the tubo-ovarian structures in infertile patients without obvious
      pelvic pathology. It aims to be an acceptable alternative to diagnostic
      laparoscopy, a standard but not innocuous procedure which infrequently reveals
      pathology in the asymptomatic patient. Transvaginal hydrolaparoscopy copy is
      performed under local anaesthesia using a small diameter optic with the patient
      in the dorsal position. Cavity distension is achieved with normal saline.
      Transvaginal hydrolaparoscopy does not provide the familiar and panoramic view of
      the pelvis given by laparoscopy, but it does have several advantages. These
      include accurate and atraumatic inspection of adnexal structures without
      manipulation, with the opportunity to perform dye hydrotubation and
      salpingoscopy. The risks of a general anaesthetic are avoided, and there is less
      risk of trauma to major vessels. The high patient acceptability makes
      transvaginal hydrolaparoscopy suitable as an early stage procedure in the
      investigation of infertility and as a repeat or second look procedure. Minor
      operative procedures such as biopsy and adhesiolysis can also be performed. In
      patients with obvious pelvic pathology, diagnostic laparoscopy will obviously
      remain the procedure of choice. Transvaginal hydrolaparoscopy deserves full
      evaluation of its accuracy, risks and benefits before it can be accepted as a new
      first line technique in gynaecological practice.

PMID- 9512238
TI  - Multiple pregnancies obtained by testicular spermatid injection in combination
      with intracytoplasmic sperm injection.
AB  - Recent studies have shown that the injection of spermatid cells into the human
      oocyte can result in normal fertilization, embryo development and even delivery
      of live, healthy offspring. In our study, 23 azoospermic cases with severe
      spermatogenetic defects in their testicular biopsy are presented. The serum
      follicle stimulating hormone (FSH) concentrations and histopathological results
      of these males have been documented and compared in terms of fertilization and
      embryo development. The mean FSH value of the azoospermic males was 15.8 +/- 2.3
      mIU/l, ranging from 1.6 to 39 mIU/l. Elongated spermatids were used in three
      cases only, as these more mature forms were mostly present in the testicular
      sample. In the remaining 20 cases, only round spermatids were found for use in
      intracytoplasmic sperm injection (ICSI). The fertilization rate with two
      pronuclei was 31.3%. The fertilization rate was found to be as high as 71% in
      three patients in the elongating and elongated spermatids group and as low as
      25.6% in the round spermatid group. A few immature, non-motile spermatozoa were
      seen in only two cases from the elongated spermatid group. However, in the
      remaining cases, no spermatozoa were observed. The number of pronuclear (PN)
      arrest was quite high when only round spermatids were used (36.1%). Total
      fertilization failure was observed in two cases from the round spermatid group
      with Sertoli cell only and germ cell aplasia. A total of three pregnancies was
      achieved in 23 cases (13.0%), two from the elongated spermatid group and one from
      the round spermatid group. One biochemical pregnancy with a round spermatid
      resulted in an early spontaneous abortion and surprisingly, the remaining
      pregnancies were achieved with elongated spermatids resulting in multiple
      pregnancies. One twin and one triplet pregnancy were established following four
      embryo transfers in each patient. The twin pregnancy resulted in a live birth
      with two healthy babies; unfortunately, the triplet pregnancy ended in an
      abortion at 11 weeks. The use of testicular spermatids in the treatment of non
      obstructive azoospermia may give hope by offering a novel treatment model. In
      cases with very severe spermatogenetic defect, even multiple pregnancies can be
      achieved with elongated spermatid cells by yielding a high implantation rate.
      However, the efficiency of round spermatids in achieving fertilization and
      pregnancy was disappointing.

PMID- 9512239
TI  - Low seminal zinc bound to high molecular weight proteins in asthenozoospermic
      patients: evidence of increased sperm zinc content in oligoasthenozoospermic
      patients.
AB  - Total seminal zinc concentration, seminal zinc fraction bound to high molecular
      weight proteins (HMW-Zn%) and zinc content in spermatozoa were assayed in the
      ejaculates of 90 asthenozoospermic patients subdivided into two study groups:
      normoasthenozoospermics (group I: n = 50) and oligoasthenozoospermics (group II:
      n = 40). The zinc concentrations of patients were compared with those of a
      control group of donors showing normal semen parameters. All samples were also
      investigated for their sperm membrane functional integrity by the hypo-osmotic
      swelling test (HOS). The results showed normal total zinc concentrations but very
      low HMW-Zn% values (P < 0.001) in seminal plasma of the two groups of
      asthenozoospermic patients compared to the controls. Furthermore higher zinc
      amounts (P < 0.001) were measured in spermatozoa of oligoasthenozoospermic
      patients compared to group I and to the control group. Oligoasthenozoospermics
      also displayed a lower HOS score (P < 0.001) compared to the other two groups.
      These data suggest that the increased unbound seminal zinc could contribute to
      the decrease of sperm motility in normoasthenozoospermic and
      oligoasthenozoospermic patients. A further impairment in sperm motility could
      occur in the oligoasthenozoospermic patients where the increase of seminal free
      zinc was followed by a major zinc uptake by spermatozoa. The higher intrasperm
      zinc content in these patients could be a reflection of their low sperm membrane
      functionality.

PMID- 9512240
TI  - Aluminium, lead and cadmium concentrations in seminal plasma and spermatozoa, and
      semen quality in Finnish men.
AB  - Aluminium, cadmium and lead concentrations in the spermatozoa and seminal plasma
      of 27 employees of two industrial companies, a refinery and a polyolefin factory,
      and 45 consecutive sperm donor candidates at a sperm bank were studied using
      atomic absorption measurements. The relationship between metal concentration and
      parameters of semen analysis was studied. A high concentration of aluminium in
      spermatozoa was correlated with decreased sperm motility. The concentrations of
      cadmium and lead were low and did not show any correlation with parameters of
      semen analysis. Aluminium may be one of the environmental pollutants causing
      impaired semen quality. The mean sperm concentrations were similar in the factory
      employees (96 x 10(6)/ml), in the sperm donor candidates of the comparison group
      (104 x 10(6)/ml) and in 352 donor candidates at the sperm bank of the Family
      Federation of Finland (107 x 10(6)/ml) between May 1993 and May 1995.

PMID- 9512241
TI  - Detrimental effects of polyvinylpyrrolidone on the ultrastructure of spermatozoa
      (Notulae seminologicae 13).
AB  - The effect of in-vitro treatment by polyvinylpyrrolidone (PVP) on the
      ultrastructure of human spermatozoa has been tested previously with the
      statistical analysis of B. Baccetti et al. (1995, J. Androl., 16, 356-371). PVP
      had a primary detrimental action on the plasma membrane, as well as on acrosomal
      and mitochondrial membranes. Furthermore, membrane damage induces deterioration
      of the chromatin, axonemal tubules, fibrous sheath, and accessory fibres.

PMID- 9512242
TI  - Meiotic products of a Klinefelter 47,XXY male as determined by sperm fluorescence
      in-situ hybridization analysis.
AB  - The meiotic segregation of 24 spermatozoa obtained from a 47,XXY male is
      described. Three-colour fluorescence in-situ hybridization with probes for
      chromosomes X, Y and 18 was used. Five spermatozoa carried an X chromosome, seven
      carried a Y, six had an XY gonosomal complement, five were missing the sex
      chromosome and one spermatozoon was presumably diploid with an XX/1818
      complement. Our results support the hypothesis that XXY cells are able to
      complete meiosis. In this patient, the percentage of spermatozoa with an abnormal
      number of sex chromosomes increased from 1/6 (17%) among spermatozoa with normal
      morphology to 11/18 (61%) in spermatozoa with abnormal morphology.

PMID- 9512243
TI  - The effects of follicular fluid from patients with different indications for IVF
      treatment on the binding of human spermatozoa to the zona pellucida.
AB  - This study compared the effects of human follicular fluid (hFF) from women with
      endometriosis, tubal factor and male factor on the zona binding capacity of human
      spermatozoa. Samples of hFF were collected from 30 patients, 10 patients for each
      of the indications of infertility, at the time of oocyte retrieval in an in-vitro
      fertilization/embryo transfer programme. The hemizona binding assay (HZA) was
      used to assess the effect of these hFF on the zona binding potential of human
      spermatozoa. The mean numbers of spermatozoa bound to the zona pellucida after
      treating the spermatozoa with hFF from endometriosis, tubal factor and male
      factor were 90.5 +/- 20.9, 108.9 +/- 22.3 and 101.2 +/- 13.4 respectively. These
      were significantly lower than their corresponding controls, the spermatozoa of
      which were incubated with Earle's balanced salt solution (endometriosis 238.7 +/-
      34.7; tubal factor 210.8 +/- 41.6; male factor 205.4 +/- 26.3; P <0.002). The
      hemizona binding index (HZI) was similar between male factor samples (52.0 +/-
      6.7) and tubal factor samples (53.8 +/- 4.2). Spermatozoa incubated with hFF from
      endometriosis patients (36.0 +/- 4.1) had an HZI that was significantly lower
      than those treated with hFF from tubal factor patients (P <0.01). Probably due to
      small sample size, the differences in HZI between endometriosis samples and male
      factor samples did not reach statistical significance (P = 0.076). These data
      suggest that there was a stronger sperm-zona binding inhibitory effect of hFF
      from patients with endometriosis than from those without the disease.

PMID- 9512244
TI  - Quantification by magnetic resonance spectroscopy of metabolites in seminal
      plasma able to differentiate different forms of azoospermia.
AB  - The aim was to determine whether proton magnetic resonance spectroscopy (1H-MRS)
      of metabolites such as glycerophosphorylcholine (GPC), choline, citrate and
      lactate in human seminal plasma can be used to differentiate (i) different
      azoospermic patients and (ii) different forms of spermatogenic failure including
      those who had undergone radiation therapy or chemotherapy. Semen samples were
      provided by men with obstructive azoospermia and spermatogenic failure who had
      serum follicle stimulating hormone (FSH) values within the normal range and
      either more or less than normal. Four prominent constituents of seminal plasma
      were identified by 1H-MRS: GPC, choline, citrate and lactate. The peak area
      ratios of choline/citrate as well as choline/lactate were significantly different
      (P < 0.01) between groups with spermatogenic failure and obstructive azoospermia.
      When the serum FSH values were normal in men with spermatogenic failure and
      obstructive azoospermia, a significant difference was found in the GPC/choline
      ratio (P < 0.001). When the FSH values were normal, the GPC/choline ratio
      appeared to be a very important parameter able to differentiate not only between
      cases of spermatogenic failure and obstructive azoospermia but also between
      different forms of spermatogenic failure. These results demonstrate the potential
      use of 1H-MRS on human seminal plasma in a new approach in the management of male
      infertility.

PMID- 9512245
TI  - High-frequency electric field trapping of individual human spermatozoa.
AB  - We present a new touch-free technique for trapping, positioning and selecting
      human spermatozoa. This can be done in free solution (culture medium) by high
      frequency electric fields. Ultramicroelectrodes fabricated by photo- and electron
      beam lithography on quartz and glass substrates were used to create field cages
      or long field channels. If the conductivity of the external salt solution is
      higher than the average value of sperm cell conductivity, negative polarization
      and negative dielectrophoresis occur. As a result, the induced cell polarization
      leads to forces repelling spermatozoa from the electrodes towards the field
      minimum. Using four planar electrodes a field funnel can be formed in which an
      individual spermatozoon is retarded while swimming. The same can be done more
      effectively in three-dimensional cages created by an octopole electrode system.
      In these systems, rapidly swimming spermatozoa could be trapped for several
      seconds but some spermatozoa stop moving if exposed to field strengths of more
      than 500 V/cm at frequencies in the MHz range. However, in stripwise and
      interdigitated electrodes, rapidly swimming sperm cells could be very well
      positioned in front of a break-electrode by a combination of electric field
      trapping and field induced laminar fluid streaming. This technique can be applied
      to bring individual spermatozoa to a defined position for characterization
      followed by sampling with capillaries.

PMID- 9512246
TI  - Guidelines on the application of CASA technology in the analysis of spermatozoa.
      ESHRE Andrology Special Interest Group. European Society for Human Reproduction
      and Embryology.

PMID- 9512247
TI  - Experiences in Hong Kong with the theory and practice of the albumin column
      method of sperm separation for sex selection.
AB  - Controversy still surrounds the human serum albumin (HSA) method for separation
      of X- and Y-bearing human spermatozoa. There is doubt about whether the procedure
      does enrich sperm samples for the chosen sex chromosome. We have applied the HSA
      separation method in a clinic in Hong Kong, using the method as described by
      Ericsson et al. [Nature, 246, 421-424 (1973)] taking care to keep the sperm
      recovery to <5% of the initial number. Aliquots of separated spermatozoa were
      examined for X- and Y-bearing spermatozoa by fluorescent in-situ hybridization
      (FISH) using appropriate DNA probes. Of 18 couples wanting boys, 13 had single
      boys, one had twin boys, and one had twins comprising one boy and one girl. Only
      three single girls were born. This success rate of 83% is significantly different
      (P < 0.001) from the usual expected ratio. There were four miscarriages, one in
      the third and one in the fourth week of pregnancy. The times of the others are
      not definitely known, but are thought to have occurred early in pregnancy. We
      lack information on three couples. The FISH procedure showed no change in the
      normal and equal numbers of X- and Y-bearing spermatozoa after the HSA separation
      procedure. This study confirmed that the HSA sperm separation method can bias the
      number of babies in favour of males. However, the theory that it does so by
      enriching the sperm samples with Y-bearing spermatozoa appears to be incorrect
      and some other theory has to be postulated. It is tentatively proposed that
      passage through the HSA inactivates X-bearing spermatozoa more than Y-bearing
      spermatozoa, even though this is not apparent simply on inspection of sperm
      motility.

PMID- 9512248
TI  - The somatostatin analogue, octreotide, modifies both steroidogenesis and IGFBP-1
      secretion in human luteinizing granulosa cells.
AB  - The effect of the somatostatin analogue octreotide on the secretion of
      progesterone and insulin-like growth factor binding protein-1 (IGFBP-1) from
      human granulosa-luteal cells was investigated. Octreotide (10(-11), 10(-10) and
      10(-9) M) alone induced a significant decrease in progesterone secretion (maximum
      suppression 69 +/- 5% of control: P < 0.0001). In contrast, treatment with
      octreotide in combination with human chorionic gonadotrophin (HCG), at 1 IU/ ml
      potentiated the stimulatory effect of HCG on progesterone secretion (HCG alone
      201 +/- 3% of control: HCG + octreotide 10(-9) M 318 +/- 16%: P < 0.001).
      Treatment with octreotide increased the secretion of IGFBP-1 (maximum stimulation
      254 +/- 25% of control: P < 0.01). No effect of HCG was seen on secretion of
      IGFBP-1. These findings raise the possibility that somatostatin may have a
      modulatory role in regulating steroidogenesis by the human corpus luteum. Further
      studies are required to establish the physiological significance of any such
      function.

PMID- 9512249
TI  - The meiotic competence of in-vitro matured human oocytes is influenced by donor
      age: evidence that folliculogenesis is compromised in the reproductively aged
      ovary.
AB  - The human oocyte appears to be particularly prone to meiotic errors, and the
      incidence of these errors is strongly influenced by maternal age. We have
      initiated studies of human oocytes from unstimulated ovaries and have observed
      age-related effects on the meiotic process in oocytes from unselected antral
      follicles. Specifically, in oocytes obtained from donors over the age of 35
      years, the majority of oocytes that extruded a first polar body in culture and
      arrested at second meiotic metaphase had aberrations in spindle formation and
      chromosome alignment. Similarly, observations of a limited number of oocytes at
      first meiotic metaphase suggest disturbances at this stage of meiosis as well.
      Finally, preliminary results of non-disjunction studies suggest that the
      frequency of errors in chromosome segregation at the first meiotic division is
      influenced by donor age in in-vitro matured oocytes as it is in oocytes
      undergoing meiotic maturation in vivo. These data provide direct evidence that
      the meiotic competence of oocytes from unstimulated ovaries declines with donor
      age. Similarly, studies of in-vitro fertilization (IVF) pregnancies in older
      women indicate that the developmental competence of the human oocyte declines
      with age. Since both meiotic and developmental competence are acquired during the
      late stages of oocyte growth, we postulate that an age-related decline in the
      process of folliculogenesis results in reduced oocyte quality and that the well
      characterized age-related increase in meiotic non-disjunction is one symptom of
      compromised oocyte growth.

PMID- 9512250
TI  - Quantification of insulin-like growth factor I receptors on granulosa cells with
      flow cytometry after follicular stimulation.
AB  - The presence of insulin-like growth factor I (IGF-I) receptors on granulosa cells
      was investigated by flow cytometric analysis. Granulosa cells were retrieved from
      follicular fluid after oocyte retrieval during assisted reproduction technology
      procedures. Whole samples of follicular fluid were pooled and the cellular
      fraction analysed. In order to analyse granulosa cells only we developed a dual
      labelling technique whereby granulosa cells were identified as CD45 negative
      cells, distinguishing them from leukocytes which are CD45 positive. Analysis of
      the IGF-I receptor was done by staining the sample with a monoclonal anti-IGF-I
      receptor antibody (alphaIR3 clone) and goat anti-mouse phycoerythrin labelled
      antibody. After identification of the presence of IGF-I receptors, receptor
      expression was quantified by calibration of the fluorescence signals. We analysed
      10 patients' samples and showed 559-1774 binding sites per granulosa cell with a
      mean value of 1125 +/- 382 (SD).

PMID- 9512251
TI  - Co-culture with assisted hatching of human embryos using Buffalo rat liver cells.
AB  - Commercially obtained Buffalo rat liver (BRL) cells were grown in monolayer
      culture. The effect of BRL cell co-culture with assisted hatching on embryo
      development, implantation and pregnancy was investigated in a population of 200
      'first-time' in-vitro fertilization (IVF) patients, subdivided into three groups
      according to the methods of fertilization [IVF; intracytoplasmic sperm injection
      (ICSI); ICSI/IVF]. Assisted hatching was performed on all embryos chosen for
      transfer. Following co-culture, the overall embryo quality, implantation rate and
      pregnancy rates were not significantly different from the controls. However, when
      grouped according to fertilization method, co-culture was found to have an impact
      on pregnancy and implantation rates in the group undergoing conventional IVF.
      Using co-culture with assisted hatching, we were able to achieve a 58% (38/65)
      clinical pregnancy rate with a 49% (32/65) live birth rate and a 26% (60/235)
      implantation rate. No changes in the pregnancy and implantation rates were
      apparent in ICSI or ICSI/IVF subgroups. This is the first prospective, randomly
      controlled study which reports the use of BRL cell co-culture for human IVF for a
      large number of patients undergoing IVF for the first time.

PMID- 9512252
TI  - Evolution of a culture protocol for successful blastocyst development and
      pregnancy.
AB  - A cell-free culture system was designed for human embryo development to the
      blastocyst stage by testing a range of culture conditions in a series of
      protocols. The culture system that was evolved has a brief 1 h exposure to
      spermatozoa and then culture of the pronucleate zygote for 2 days in IVF-50
      medium. Two or three embryos were cultured together in 20 microl microdrops of
      medium under oil. Embryos were then regrouped and two or three at a similar stage
      were cultured together in 50 microl microdrops of Gardner's G2 medium under oil
      from days 3 to 5. Embryos were transferred to fresh G2 medium on day 5 and
      cultured for a further 1 or 2 days (day 6 or 7). No serum was used in any of the
      cultures. The embryo transfer medium and G2 medium were supplemented with human
      serum albumin. The zonae of all blastocysts to be transferred to patients were
      completely removed enzymatically. Using this protocol, 52% of zygotes developed
      to blastocysts and 34 out of 35 patients treated received 82 blastocysts and 11
      morulae on day 5 or 6. Twenty-one fetal sacs with positive heartbeats (23%
      implantation rate) were detected in 13 ongoing pregnancies (38% pregnancy
      rate/transfer or 37%/patient treated). We anticipate that further improvements in
      embryo development and the selection of viable embryos can be achieved using this
      simple and effective culture system.

PMID- 9512253
TI  - Resumption of mitosis during post-thaw culture: a key parameter in selecting the
      right embryos for transfer.
AB  - This retrospective study of 701 thaw cycles analysed the clinical importance of
      whether or not embryos resumed mitosis during 24 h of post-thaw culture. A total
      of 3360 frozen embryos were thawed; 1922 embryos survived the freeze-thaw
      procedure with at least one intact blastomere and were then cultured for 24 h
      before transfer. All transfers were registered into either the 'cleaved embryo
      group' (n = 459), which was defined as transfers where at least one of the
      transferred embryos cleaved during the post-thaw culture period, or the 'non
      cleaved embryo group' (n = 153), where none of the transferred embryos cleaved
      during the post-thaw culture period. A total of 1408 thawed embryos were
      transferred in 612 cycles; 459 embryo transfers were in the cleaved embryo group,
      resulting in an implantation rate of 10%, significantly higher than the 4% in the
      non-cleaved embryo group (P = 0.0003). A total of 130 pregnancies (28% per
      transfer) were obtained in the cleaved embryo group which was significantly
      higher than the 17 pregnancies (11% per transfer) obtained in the non-cleaved
      embryo group (P = 0.0001). However, the average number of transferred embryos was
      significantly higher in the cleaved embryo group (2.46 +/- 0.03) compared to the
      non-cleaved embryo group (1.82 +/- 0.07). No difference was found in the age of
      the women between the two groups. When analysing transfers where all transferred
      embryos had cleaved during the post-thaw culture period the clinical pregnancy
      rate increased significantly from 13% transferring two embryos to 36%
      transferring three embryos (P = 0.0136). In this latter subgroup an implantation
      rate as high as 17% was obtained. The overall multiple pregnancy rate was 16%.
      The multiple pregnancy rate was 19% in the cleaved embryo group. In conclusion,
      24 h post-thaw culture may allow a better selection of the embryos and thereby we
      may be able to increase the implantation and pregnancy rates. This may enable us
      further to reduce the number of embryos transferred.

PMID- 9512254
TI  - Early cleavage of human embryos to the two-cell stage after intracytoplasmic
      sperm injection as an indicator of embryo viability.
AB  - In-vitro fertilization (IVF) embryos are selected for transfer on the basis of
      morphology and rate of development. However, when a number of embryos have
      similar characteristics, the selection of the best embryos is left to chance.
      Recently, we proposed a simple, novel method to overcome this problem, based on
      pre-selection of embryos cleaving early to the two-cell stage. In this study we
      have adopted the same method to choose embryos fertilized after intracytoplasmic
      sperm injection (ICSI). Fertilized embryos that had cleaved to the two-cell stage
      by 27 h post-injection were designated as 'early cleavage' embryos, while those
      that had not yet reached the two-cell stage were designated as 'no early
      cleavage'. In all cases, the early cleavage embryos were transferred when
      available. Early cleavage was observed in 54 (61.4%) of the 88 cycles assessed.
      There were significantly (P = 0.04) more clinical pregnancies in the early
      cleavage group, 14/54 (25.9%), compared with the no early cleavage group 2/34
      (3.2%). No differences between the groups were found when comparing key
      parameters (age, stimulation protocol and semen characteristics) of the couples.
      Using the ICSI technique, we have shown that early cleavage to the two-cell stage
      is not influenced by the timing of fertilization, and is more likely due to
      intrinsic factors within the oocyte or embryo that promote embryo cleavage after
      fertilization.

PMID- 9512255
TI  - Endometrial thickness and oestradiol concentration in women with bleeding
      complaints during use of Norplant implants.
AB  - The objective of this study was to measure oestradiol, progesterone and
      endometrial development among Norplant implant users with bleeding complaints.
      Seventy-six volunteers complaining of prolonged/frequent bleeding were enrolled.
      Oestradiol, progesterone and endometrial thickness (assessed by vaginal
      ultrasound) were determined at that visit. Two thirds of the women had low
      oestradiol (< 50 pg/ml) and all except one had low progesterone concentrations (<
      3 ng/ml). A total of 68% had a very thin endometrium (< 3 mm). A subgroup of 21
      women were followed twice a week for 8 consecutive weeks. Oestradiol and
      progesterone concentrations remained low during the continuous bleeding episodes
      or short bleeding-free intervals (< or = 15 days), yet increased five- to sixfold
      (253.4 +/- 142.2 pg/ml) in long bleeding-free intervals. Endometrial thickness
      remained thin irrespective of the differences in bleeding patterns and
      oestradiol. We conclude that Norplant implant users with bleeding complaints are
      usually characterized by low oestradiol concentrations, absence of luteal
      activity and thin endometrium. A good correlation exists with increasing
      oestradiol concentrations and longer bleeding-free intervals, but this is not
      manifested by increased endometrial thickness. However, few subjects bleed with
      relatively high oestradiol concentrations, therefore a better understanding of
      the intimate disturbances related to endometrial bleeding in users of long-acting
      progestins is still pending.

PMID- 9512256
TI  - Uterine leiomyomas reduce the efficacy of assisted reproduction cycles: results
      of a matched follow-up study.
AB  - A matched follow-up study design was used to test the hypothesis that pregnancy
      rates following assisted reproduction procedures do not differ between women with
      or without intramural or sub-serosal uterine leiomyomas. Women undergoing their
      first in-vitro fertilization (IVF)-embryo transfer or zygote intra-Fallopian
      transfer (ZIFT) cycle between January 1993 and June 1995 were included. Cases
      (women with leiomyomas) were matched 1:1 with the next consecutive control (women
      without leiomyomas) according to age, number of embryos transferred, embryo
      grade, and the route of embryo transfer (uterine or Fallopian). Assisted
      reproduction cycles were performed in an identical manner, independent of the
      presence or absence of uterine leiomyomas. The main outcomes measured were
      clinical pregnancy and delivery rates. A total of 182 cycles was evaluated. Of
      the 91 assisted reproduction cycles performed in the leiomyoma group, there were
      34 clinical pregnancies (37%) and 30 deliveries (33%). Of the 91 assisted
      reproduction cycles in the control group, there were 48 clinical pregnancies
      (53%) and 44 deliveries (48%). The Mantel-Haenszel estimate of relative risk
      indicated that the presence of a uterine leiomyoma significantly reduced the
      chance for a clinical pregnancy or delivery. These findings suggest that
      leiomyomas are associated with a reduction in the efficacy of assisted
      reproduction cycles.

PMID- 9512257
TI  - Uterine myomata and outcome of assisted reproduction.
AB  - The aim of this work was to study the effect of uterine myomata on the
      implantation rate and outcome in in-vitro fertilization (IVF) and
      intracytoplasmic sperm injection (ICSI). Among 406 patients, 51 (12.6%) were
      found to have uterine corporeal myomata. Twelve patients were excluded from the
      study as they had large myomata, submucous myomata or intramural myomata
      encroaching on the cavity. These patients were advised to have myomectomy before
      being enrolled in the IVF/ICSI programme. The remaining patients (n = 39) were
      sorted according to the number, site and size of the myomata as assessed by
      transvaginal sonography. Three patients had more than one myoma. Most of the
      myomata were subserous (72.7%) and the mean diameter of the myomata was 3.5 +/-
      0.9 cm. A control group (n = 367) was chosen with normal uteri and no history of
      uterine reconstruction surgery. The mean age of myoma patients was 34.7 +/- 3.6
      years as compared to 34.0 +/- 4.4 years in the control group. The age, period of
      infertility, body mass index, duration and number of human menopausal
      gonadotrophin ampoules needed for stimulation, oestradiol levels, number of
      oocytes retrieved and the fertilization rate were not significantly different in
      the myoma patients compared to the control group. Fifteen myoma patients (38.5%)
      subsequently showed one or more pregnancy sacs on ultrasonography of which three
      (20%) spontaneously aborted during the first trimester and two (13.3%) had
      preterm labour, as compared to 123 (33.5%), 19 (15.5%) and nine (7.3%)
      respectively, among the control group (P = 0.27, 0.33 and 0.21). In conclusion,
      uterine corporeal myomata, not encroaching on the cavity and <7 cm in mean
      diameter, do not affect the implantation or miscarriage rates in IVF or ICSI.

PMID- 9512258
TI  - Treatment, failures and complications of ectopic pregnancy: changes over a 20
      year period.
AB  - Data from all 225 women operated on for ectopic pregnancy in 1992-1994 at
      Sahlgrenska University Hospital were collected and compared with three previous
      cross-sectional investigations from our hospital (1975-1979, 1981-1982 and 1986
      1987) in order to evaluate the extent to which surgical treatment and post
      operative complications have changed over a 20 year period. Laparoscopic surgery,
      which was not possible in the 1970s, was used in almost 85% of the ectopic
      pregnancies in 1992-1994. Conservative treatment was still the most frequently
      used technique. The complication rate was 1.2% in 1975-1979 when only
      laparotomies were carried out. After the introduction of laparoscopic surgery
      (1986-1987), the complication rate rose significantly (7.3%) and continued to
      increase even when this procedure was established as routine (14.2% in 1992
      1994). Post-operative complications were most frequent after conservative
      laparoscopic surgery (24.4%) while there were no complications after
      laparotomies. In spite of increasing complication rates the frequency of patients
      in pre-shock, as well as the proportion of patients with heavy intra-abdominal
      bleeding and tubal rupture, decreased over time.

PMID- 9512259
TI  - Contribution of calcium-sensitive potassium channels to NS1619-induced relaxation
      in human pregnant myometrium.
AB  - Large-conductance, calcium-sensitive potassium channels (BK(Ca)) are found at
      high density in the pregnant human myometrium. We have investigated, using
      isolated myometrial strips and freshly dispersed human myometrial cells, the
      action of a novel drug (NS1619) which has potassium channel opening activity.
      Isometric tension experiments demonstrated that NS1619 has a potent, relaxant
      effect on the pregnant human myometrium. Using both the inside-out and outside
      out configurations of the patch-clamp technique, NS1619 appears to act directly
      on myometrial BK(Ca) channels to stimulate channel activity by increasing the
      time spent in the open state by this group of potassium channels. Consequently,
      the myometrial BK(Ca) channel may be a novel target site for drug intervention in
      clinical conditions, e.g. failure to labour, preterm labour or dysmenorrhoea,
      which may require either the augmentation or inhibition of uterine K+ channel
      activity.

PMID- 9512260
TI  - Effect of gestational age on in-vitro responses of pregnant rat aorta.
AB  - The hypothesis that the changes in vascular reactivity seen during pregnancy are
      determined by the gestational age was examined. Experiments were designed to
      investigate changes in vascular responses with progression of pregnancy. The
      contractile responses to potassium and phenylephrine (in the presence and absence
      of N(omega)-nitro-L-arginine methyl ester, a nitric oxide synthase inhibitor) and
      the relaxant responses to acetylcholine and sodium nitroprusside were measured in
      isolated aortic rings from pregnant rats at various stages of gestation and from
      non-pregnant female rats. Potassium-evoked contractile response was higher early
      in pregnancy and was decreased at term (P < 0.05). The contractile response to
      phenyllephrine was decreased and the relaxant response to acetylcholine was
      increased in early pregnancy (P < 0.05). Inhibition of nitric oxide synthase
      caused an increase in the contractile response to phenylephrine in all the
      groups, but the attenuation of the response in early pregnancy was maintained (P
      < 0.05). There was a small decrease in the maximal relaxant response to sodium
      nitroprusside at term (P < 0.05). It was concluded that the effects of pregnancy
      on the responses of rat aorta in vitro vary at different stages of gestation.
      Vascular resistance may be lowered by changes in vascular reactivity in early
      gestation and by a decrease in the contractile potential of the vasculature
      during the later stages.

PMID- 9512261
TI  - Second-trimester maternal serum screening for Down's syndrome: free beta-human
      chorionic gonadotrophin (HCG) and alpha-fetoprotein, with or without unconjugated
      oestriol, compared with total HCG, alpha-fetoprotein and unconjugated oestriol.
AB  - The aim of our study was to compare three protocols for second-trimester maternal
      serum screening for Down's syndrome in the same serum samples, using two triple
      tests [total human chorionic gonadotrophin (HCG), alpha-fetoprotein, unconjugated
      oestriol; and free beta-HCG, alpha-fetoprotein, unconjugated oestriol] and a
      double test (free beta-HCG and alpha-fetoprotein). The three protocols were
      compared in a series of 23 serum samples from Down's syndrome pregnancies and in
      a cohort of 2516 pregnant women receiving routine antenatal care between June
      1992 and June 1993. Among the 23 affected cases, at a cut-off risk of 1:380, the
      detection rate of Down's syndrome was comparable with the double test (74%;
      17/23) and the triple tests (65%; 15/23) (not significantly different). At the
      same cut-off risk, in the cohort of 2516 pregnant women screened between 15 and
      18 weeks gestation, both protocols using free beta-HCG achieved a significant
      reduction of the number of false positive cases (P = 0.013 and 0.004 for double
      and triple tests respectively). We conclude that, compared to total HCG, alpha
      fetoprotein and unconjugated oestriol, use of free beta-HCG and alpha-fetoprotein
      represents a better second-trimester screening test for Down's syndrome, because
      it significantly decreases the false positive rate at a lower running cost. The
      addition of unconjugated oestriol to the double test adds no further advantage.

PMID- 9512262
TI  - Cancer of the colon in an egg donor: policy repercussions for donor recruitment.
AB  - This paper describes the tragic case of a young woman who died of cancer of the
      colon after successfully donating eggs to her younger sister. Although there is
      no direct link between her operation and the subsequent development of bowel
      carcinoma, this case imparts a feeling of unease when seen in conjunction with
      other cases reported during the last few years. It is a reminder that little is
      known of the long-term consequences of some aspects of assisted conception. Women
      undergoing ovarian stimulation for themselves or a matched recipient have the
      right to be advised, in an agreed format, that there is some concern about
      unproven potential risks from the stimulatory drugs. The safety of egg donors
      must assume priority over all other considerations, including lack of donors or
      any moral position. The recent decision by the Human Fertilisation and Embryology
      Authority (HFEA) to withdraw any form of payment or recompense to egg donors does
      not seem to us to be based on a balance of scientific advances, patient needs and
      the ethics of gamete supply. They state that the intention to withdraw payments
      was implicit in the 1990 Human Fertilisation and Embryology (HFE) Act. However
      the Act was based on the Warnock report made 6 years earlier. Even in 1990 ovum
      donation was uncommon and fertility drugs had not yet caused any unease. The Act
      provided the HFEA with discretionary powers to issue directions so that the
      future policies would be consistent with any emerging new medical evidence. It is
      imperative that the HFEA provide convincing evidence on how the current policy of
      payment to donors harms society, donors or recipients, and how in the UK the new
      policy will improve medical practice in assisted conception. Successful pilot
      studies must precede the implementation of any new policy. Failure to do this
      could cause irreversible harm to the practice of assisted conception using donor
      gametes, which will ultimately be against the basic aims of the 1990 HFE Act.

PMID- 9512263
TI  - Some socio-cultural and psychological aspects of infertility.
AB  - A link is suggested to exist between any unexplained or relatively unexplained
      lowering of fertility and an inner sensitivity, largely or wholly unconscious, to
      some situation that renders it an unsuitable time or place for the individual or
      couple to allow the arrival of a baby. The psycho-social and intra-psychic
      processes involved in such situations can be quite subtle, and the question of
      their neuroendocrinological connections presents an intriguing area for future
      research. Some sociological, anthropological and psycho-analytical findings
      relevant for this theme are outlined here. Three illustrative vignettes are
      presented, the clinical material on which the findings are based is summarized
      briefly, and a discussion is held about what appears to be required in treatment.

PMID- 9512264
TI  - Septate uterus.

PMID- 9512265
TI  - Side of ovulation in spontaneous cycles and during stimulation for in-vitro
      fertilization.

PMID- 9512266
TI  - Schreiner organs: a new craniate chemosensory modality in hagfishes.
AB  - An extensive system of sensory organs resembling taste buds was previously known
      in the skin of hagfishes. These sensory organs, called here Schreiner organs, are
      found throughout the epidermis of both Eptatretus stoutii and Myxine glutinosa.
      They are found also at high densities in the prenasal sinus, nasopharyngeal duct,
      and pharynx, and at lower densities in the oral and velar chambers. Schreiner
      organs are multicellular aggregates composed of acetylated tubulin-immunoreactive
      receptor cells and nonimmunoreactive cells. A considerable range of variation was
      found in Schreiner organ morphology, but discrete classes of organs could not be
      recognized. Schreiner organs are innervated by all sensory trigeminal rami, the
      glossopharyngeal/vagal nerve, and cutaneous rami of spinal nerves, but not by the
      facial nerve. The central projections of these rami form a continuous tract in
      the trigeminal sensory zone and the dorsolateral funiculus of the spinal cord.
      Some Schreiner organs may be represented in the nucleus of the solitary tract,
      but this structure is certainly not the primary recipient zone of Schreiner organ
      afferents. In light of these systemic differences between vertebrate taste
      systems and the Schreiner organ system of hagfishes, it is concluded that
      Schreiner organs are not homologous to taste buds. This sensory modality of
      hagfishes has no direct homolog in vertebrates and appears to be a specialization
      of hagfishes, perhaps derived from the primitive somatosensory system of the
      earliest craniates.

PMID- 9512267
TI  - Single Purkinje cell can innervate multiple classes of projection neurons in the
      cerebellar nuclei of the rat: a light microscopic and ultrastructural triple
      tracer study in the rat.
AB  - Two different populations of projection neurons are intermingled in the
      cerebellar nuclei. One group consists of small, gamma-aminobutyric acid
      containing (GABAergic) neurons that project to the inferior olive, and the other
      group consists of larger, non-GABAergic neurons that provide an input to one or
      more, usually premotor, centers in the brainstem, such as the red nucleus, the
      thalamus, and the superior colliculus. All cerebellar nuclear neurons are
      innervated by GABAergic Purkinje cells. In this study, we investigated whether
      individual Purkinje cells of the C1 zone of the paramedian lobe of the rat
      innervate both groups of projection neurons in the anterior interposed nucleus.
      Two different, retrogradely transported tracers, either cholera toxin beta
      subunit (CTb) or wheat germ agglutinin coupled to horseradish peroxidase (WGA
      HRP) and a gold lectin tracer were injected into the red nucleus and the inferior
      olive, respectively, whereas Purkinje cell axons were anterogradely labeled with
      biotinylated dextran amine (BDA) injected into the paramedian lobule. Cerebellar
      nuclear sections studied with the light microscope demonstrated a close relation
      of varicosities from BDA-labeled Purkinje cell axons with both gold lectin- and
      CTb-labeled neurons. Branches of individual axons could be traced to both
      retrogradely labeled cell populations. At the ultrastructural level, synapses of
      labeled Purkinje cell terminals with profiles of WGA-HRP-labeled projection
      neurons predominated over contacts with gold lectin-containing neurons. Nine out
      of 367 investigated BDA-labeled terminals were observed to be presynaptic to a
      WGA-HRP-labeled profile as well as to a gold lectin-labeled profile. This
      indicates that nuclear cells that project to the inferior olive as well as those
      that project to premotor centers are under the influence of the same Purkinje
      cells. Such an arrangement would suggest an in-phase cortical modulation of the
      activation patterns of the inhibitory cells that project to the inferior olive
      and excitatory cells that project to premotor nuclei, which could explain why
      olivary neurons, especially those of the rostral part of the dorsal accessory
      olive, appear to be unresponsive to stimuli generated during active movement.

PMID- 9512268
TI  - Chemically defined neuron groups and their subpopulations in the glomerular layer
      of the rat main olfactory bulb: III. Structural features of calbindin D28K
      immunoreactive neurons.
AB  - The present study analyzed three-dimensional structural features and synaptic
      contacts of morphologically and chemically identified calbindin D28K
      immunoreactive neurons in the glomerular layer of the rat main olfactory bulb by
      means of combined confocal laser scanning light microscopy, high-voltage electron
      microscopy and electron microscopic serial section/three-dimensional
      reconstruction. Most of calbindin D28K-immunoreactive neurons were identified as
      the periglomerular cell type by combined high-voltage electron microscopic and
      confocal laser scanning light microscopic observations, and the minority were the
      short-axon cell type and others. The combined confocal laser scanning light
      microscopic and electron microscopic study revealed that the calbindin D28K
      immunoreactive neurons exhibited unique synaptic contact patterns; they received
      asymmetrical synapses from presumed mitral/tufted dendrites and made conversely
      symmetrical synapses with them. About 30% of asymmetrical postsynaptic sites and
      about 40% of symmetrical presynaptic sites formed reciprocal pairs of synapses.
      Calbindin D28K-immunoreactive dendrites and somata also received synapses from
      GABA-like-immunoreactive profiles containing numerous pleomorphic, and a few
      dense-cored, vesicles. On the other hand, surprisingly, calbindin D28K
      immunoreactive neurons had almost no synaptic contacts from olfactory nerve
      terminals. The present study clearly revealed that calbindin D28K-immunoreactive
      neurons are a type of periglomerular cell involving unique synaptic contacts that
      have not been reported so far, and thus indicated that so-called periglomerular
      cells should be heterogeneous in their synaptic connections as well as in their
      chemical and structural features.

PMID- 9512269
TI  - Uptake and release of neurotransmitter candidates, [3H]serotonin, [3H]glutamate,
      and [3H]gamma-aminobutyric acid, in taste buds of the mudpuppy, Necturus
      maculosus.
AB  - Neurotransmitters in vertebrate taste buds have not yet been identified with
      confidence. Serotonin, glutamate, and gamma-aminobutyric acid (GABA) have been
      postulated, but the evidence is incomplete. We undertook an autoradiographic
      study of [3H]serotonin, [3H]glutamate, and [3H]GABA uptake in lingual epithelium
      from the amphibian, Necturus maculosus, to determine whether taste bud cells
      would accumulate and release these substances. Lingual epithelium containing
      taste buds was incubated in low concentrations (0.4-6 microM) of these tritiated
      transmitter candidates and the tissue was processed for light microscopic
      autoradiography. Merkel-like basal taste cells accumulated [3H]serotonin. When
      the tissue was treated with 40 mM K+ after incubating the tissue in
      [3H]serotonin, cells released the radiolabelled transmitter. Furthermore,
      depolarization (KCl)-induced release of [3H]serotonin was Ca-dependent: if Ca2+
      was reduced to 0.4 mM and 20 mM Mg2+ added to the high K+ bathing solution,
      Merkel-like basal cells did not release [3H]serotonin. In contrast, [3H]glutamate
      was taken up by several cell types, including non-sensory epithelial cells,
      Schwann cells, and some taste bud cells. [3H]glutamate was not released by
      depolarizing the tissue with 40 mM K+. [3H]GABA uptake was also widespread, but
      did not occur in taste bud cells. [3H]GABA accumulated in non-sensory epithelial
      cells and Schwann cells. These data support the hypothesis that serotonin is a
      neurotransmitter or neuromodulator released by Merkel-like basal cells in
      Necturus taste buds. The data do not support (nor rule out) a neurotransmitter
      role for glutamate or GABA in taste buds.

PMID- 9512270
TI  - Telencephalic ascending gustatory system in a cichlid fish, Oreochromis (Tilapia)
      niloticus.
AB  - Central fiber connections of the gustatory system were examined in a percomorph
      fish Oreochromis (Tilapia) niloticus by means of the horseradish peroxidase
      (HRP), biocytin, and carbocyanine dye tracing methods. The primary gustatory
      areas in tilapia are the facial, glossopharyngeal, and vagal lobes of the
      medulla. The secondary gustatory nucleus (SGN) is a dumb-bell-shaped structure
      located in the isthmic region. In the SGN, there are two or three layers of
      neurons lining the ventromedial periphery of the nucleus and a molecular layer
      constituting of the major part of the nucleus. The SGN receives bilateral
      projections from the facial lobes and ipsilateral projections from the
      glossopharyngeal and vagal lobes. Ascending fibers originating from the SGN form
      the ipsilateral tertiary gustatory tract. A major part of the tract courses
      rostrally and terminates ipsilaterally in several diencephalic nuclei: the
      preglomerular tertiary gustatory nucleus (pTGN), the posterior thalamic nucleus,
      the nucleus diffusus lobi inferioris, the nucleus centralis of inferior lobe, and
      the nucleus recessus lateralis. The remaining small fiber bundle enters the
      medial and lateral forebrain bundles and terminates directly in two telencephalic
      regions; the area ventralis pars intermedia (Vi) and the area dorsalis pars
      posterior (Dp). Ascending fibers from the pTGN pass through the lateral forebrain
      bundle and terminate ipsilaterally in the dorsal region of area dorsalis pars
      medialis (dDm) of the telencephalon. Following biocytin injections into the dDm,
      small, round cells were labeled in the pTGN. After biocytin injections into the
      Vi and Dp of the telencephalon, retrogradely labeled cells were found in the
      ipsilateral SGN. The results show that the ascending fiber connections of the
      central gustatory system in the percomorph teleost tilapia are essentially
      similar to those of mammals. That is, the pathway from the primary gustatory
      areas (facial, glossopharyngeal, and vagal lobes) through the SGN and pTGN to the
      dDm in tilapia corresponds with the mammalian gustatory pathway from the solitary
      nucleus through the pontine taste areas (nucleus parabrachialis) and the thalamic
      relay nucleus (ventral posteromedial nucleus) to gustatory neocortices. In
      addition, the pathway from the primary gustatory areas through the SGN to the Vi
      and Dp in tilapia corresponds with the pathway from the solitary nucleus through
      the pontine taste areas to the amygdala in mammals.

PMID- 9512271
TI  - Galanin/GMAP- and NPY-like immunoreactivities in locus coeruleus and
      noradrenergic nerve terminals in the hippocampal formation and cortex with notes
      on the galanin-R1 and -R2 receptors.
AB  - By using immunofluorescence methodology, extensive galanin (GAL) and GAL message
      associated peptide (GMAP)-positive terminal networks were observed in the
      hippocampal formation. The majority of the GAL/GMAP fibers were dopamine beta
      hydroxylase- (DBH) positive, that is, they were noradrenergic. This finding was
      established with GAL/GMAP-DBH double-staining and with 6-hydroxy-dopamine
      treatment, which totally abolished all fibers in which GAL/GMAP and DBH
      coexisted. Also, reserpine treatment caused a marked depletion of GAL. No
      evidence for GAL/GMAP coexistence with 5-hydroxytryptamine was obtained. In the
      ventral hippocampus, GAL/GMAP-, DBH-negative fibers were seen in the stratum
      oriens, the anterior stratum radiatum, along the granule cell layer and in the
      strata oriens and alveus. In the locus coeruleus (LC), around 80% of the GMAP
      positive neurons contained neuropeptide tyrosine (NPY), and about 40% of the NPY
      positive neurons expressed GMAP. GAL-R1 receptor mRNA was expressed in
      Barrington's nucleus (close to the LC), but was not detected in the hippocampal
      formation/dorsal cortical areas. GAL-R2 receptor mRNA was found in the granule
      cell layer in the dentate gyrus. The present results show that most, but not all,
      immunohistochemically detectable GAL/GMAP in the hippocampal formation/dorsal
      cortex is present in noradrenergic nerve terminals originating in the LC, which
      has a robust GAL/GMAP synthesis. The functional role of GAL may be related to
      noradrenaline, possibly by a presynaptic action. However, the presence of GAL in
      other systems and of GAL-R2 receptor mRNA in granule cells also indicates other
      targets.

PMID- 9512272
TI  - Axotomy-induced neuronal death and reactive astrogliosis in the lateral
      geniculate nucleus following a lesion of the visual cortex in the rat.
AB  - Following a unilateral lesion of the visual cortex (cortical areas 17, 18, and
      18a) in adult rats, neurons in the ipsilateral dorsal lateral geniculate nucleus
      (LGN) are axotomized, which leads to their atrophy and death. The time course of
      this neuronal degeneration was studied quantitatively, and the astroglial
      response was examined with glial fibrillary acidic protein immunohistochemistry.
      More than 95% of the neurons in the ipsilateral LGN survive during the first 3
      days following a lesion of the visual cortex. However, in the next 4 days,
      massive neuronal death ensues, reducing the number of surviving neurons to
      approximately 33% of normal by the end of the first postoperative week. Between 2
      weeks and 24 weeks postoperatively, the number of neurons present in the LGN
      declines very gradually from 34% to 17% of normal. Three days after a lesion of
      the visual cortex, the mean cross-sectional areas of ipsilateral LGN neurons are
      13% smaller than normal (87%). By 1 week after the operation, surviving LGN
      neurons have atrophied to 66% of their normal area. Subsequently, the size of
      surviving neurons declines slowly to approximately 50% of normal at 24 weeks
      after the cortical lesion. Astrocytes in the ipsilateral LGN also react to
      cortical damage. At 1 day after a lesion of the visual cortex, glial fibrillary
      acidic protein immunoreactivity in the LGN is almost undetectable, but a distinct
      increase in immunoreactivity is seen at 3 days. Immunoreactivity peaks between 1
      week and 2 weeks postoperatively and, thereafter, remains intense for at least 24
      weeks. Thus, following a lesion of the visual cortex, the somata of neurons in
      the LGN remain essentially normal morphologically for about 3 days before the
      onset of rapid atrophy and death. Moreover, most of the neural cell death that
      occurs in the LGN after axotomy takes place in the last half of the first
      postoperative week.

PMID- 9512273
TI  - Long-term protection of axotomized neurons in the dorsal lateral geniculate
      nucleus in the rat following a single administration of basic fibroblast growth
      factor or ciliary neurotrophic factor.
AB  - We have studied the long-term effects of basic fibroblast growth factor (bFGF)
      and ciliary neurotrophic factor (CNTF) on axotomy-induced cell death in the
      dorsal lateral geniculate nucleus (LGN) of adult rats. LGN neurons were
      axotomized by a visual cortex lesion in 31 adult rats. A gelatin sponge soaked in
      a solution of bFGF, CNTF, or saline (control) was placed on the surface of the
      lesion, and the animals were allowed to survive for 1-12 weeks. Compared with
      controls, no major improvement was noted in the mean cross-sectional area of
      surviving LGN neurons in rats treated with bFGF or CNTF at any survival time.
      However, treatment with either factor significantly increased the number of
      surviving neurons at each survival time. At 1 week, the survival of LGN neurons
      in rats treated with bFGF or CNTF was 136% and 131% greater, respectively, than
      in controls. At 12 weeks, the number of surviving LGN neurons in bFGF- and CNTF
      treated rats exceeded that seen in controls by 114% and 58%, respectively. Thus,
      a single administration of bFGF or CNTF following axotomy reduced neuronal death
      for long periods of time, but could not prevent atrophy. A single treatment with
      bFGF or CNTF, therefore, may block the full execution of a cell death program,
      but cannot prevent its initiation. Alternatively, the transduction pathways for
      maintaining cell size and preventing cell death may not be identical, and bFGF
      and CNTF applied as described above may be effective in activating one pathway
      but not the other.

PMID- 9512274
TI  - Coated self-expanding metal stents versus latex prostheses for esophagogastric
      cancer with special reference to prior radiation and chemotherapy: a controlled,
      prospective study.
AB  - BACKGROUND: Self-expanding metal stents seem to be safer than conventional
      prostheses for palliation of malignant esophagogastric obstruction. However,
      recurrent dysphagia caused by tumor ingrowth in uncoated types remains a problem.
      In addition, prior radiation and/or chemotherapy may entail an increased risk of
      complications. METHODS: Seventy-five patients with an esophagogastric carcinoma
      were randomly assigned to placement of a latex prosthesis under general
      anesthesia or a coated, self-expanding metal stent under sedation. At entry,
      patients were stratified for location of the tumor in the esophagus or cardia and
      for prior radiation and/or chemotherapy. RESULTS: Technical success and
      improvement in dysphagia score were similar in both groups. Major complications
      were more frequent with latex prostheses (47%) than with metal stents (16%) (odds
      ratio 4.07: 95% CI [1.35, 12.50], p = 0.014). Recurrent dysphagia was not
      different between latex prostheses (26%) and metal stents (24%). Hospital stay
      was longer, on average, after placement of latex prostheses than metal stents
      (6.3 +/- 5.2 versus 4.3 +/- 2.3 days; p = 0.043). Only prior radiation and/or
      chemotherapy increased the risk of specific device-related complications with
      respect to the esophagus (12 of 28 [43%] versus 8 of 47 [17%]; odds ratio 3.66:
      95% CI [1.24, 10.82], p = 0.029). CONCLUSIONS: Coated, self-expanding metal
      stents are associated with fewer complications and shorter hospital stay as
      compared with latex prostheses, and prior radiation and/or chemotherapy increases
      the risk of device-related complications with respect to the esophagus.

PMID- 9512275
TI  - Endoscopic ultrasound-guided, 18-gauge, fine needle aspiration biopsy of the
      pancreas using a 2.8 mm channel convex array echoendoscope.
AB  - BACKGROUND: Previous studies have reported on endoscopic ultrasound-guided, fine
      needle aspiration biopsy using 22- to 25-gauge needles. We evaluated the
      histologic and cytologic yield of endoscopic ultrasound-guided, fine needle
      aspiration biopsy of the pancreas using an 18-gauge, Menghini-type core needle.
      METHODS: Fine needle aspiration biopsy was performed in conjunction with a
      prototype 2.8 mm channel convex array echoendoscope. The core specimen was placed
      in formalin for cell block, and residual material was expelled on slides for
      cytology. Definitive diagnosis was established by surgery or clinical follow-up.
      RESULTS: Of 45 patients who underwent fine needle aspiration biopsy, the needle
      failed to penetrate indurated pancreatic lesions in five. An average of 2.6
      passes were performed in the remaining patients. Sufficient material for a
      histologic and/or cytologic diagnosis was obtained in 40 patients (histologic and
      cytologic yield of 68% and 75%, respectively). Combining the results of histology
      and cytology, the sensitivity and specificity for detection of malignancy was 76%
      and 100%, respectively. Histology confirmed the cytologic findings in 35
      patients, providing additional tissue specific information. In three cases
      histology established a diagnosis of malignancy where cytology was not
      conclusively malignant. However, in three cases of surgically confirmed
      malignancy histology failed to detect malignancy, whereas cytology showed
      suspicious or malignant cells. The sensitivity of histology and cytology alone in
      detecting malignancy was 53% and 70%, respectively. Mild pancreatitis occurred
      after pancreatic fine needle aspiration biopsy in one patient. CONCLUSION: Core
      specimens for histology can be safely obtained using an 18-gauge needle.
      Histology provides tissue-specific information that complements cytology, but
      histology is less sensitive than cytology in detecting malignancy.

PMID- 9512276
TI  - Endoscopic management of biliary strictures in liver transplant recipients:
      effect on patient and graft survival.
AB  - BACKGROUND: Biliary strictures in liver transplant recipients cause significant
      morbidity and can lead to reduced patient and graft survival. METHODS: Of 251
      liver transplant recipients, 22 patients with biliary strictures were categorized
      into two groups: donor hepatic duct (n = 12) or anastomotic (n = 10). Strictures
      were dilated and stented. Endoscopic therapy was considered successful if a
      patient did not require repeat stenting or dilation for 1 year. RESULTS: Patient
      and graft survival did not differ significantly in the 22 patients compared with
      patients without strictures (relative risk of death and graft survival 1.8 and
      1.3). Donor hepatic duct strictures required significantly longer therapy than
      anastomotic strictures (median days 185 versus 67, p = 0.02). Twenty-two months
      after the first endoscopic treatment, 73% of the donor hepatic duct stricture
      group were stent free compared with 90% of the anastomotic group (p = 0.02). The
      former group had significantly more (p < 0.05) hepatic artery thrombosis (58.3%
      versus 10%), cholangitis (58.3% versus 30%), choledocholithiasis (91% versus
      10%), and endoscopic interventions. No patient undergoing endoscopic treatment
      required retransplantation or biliary reconstruction during a median follow-up of
      35.7 months. CONCLUSION: Endoscopic therapy of biliary strictures after liver
      transplantation is effective and is not accompanied by reduced patient or graft
      survival.

PMID- 9512277
TI  - Laparoscopic observations of congenital anomalies of the liver.
AB  - BACKGROUND: A good knowledge of acquired morphologic changes and congenital
      anomalies requires precise understanding of pathologic conditions of the visceral
      organs. The aim of the present study was to systematically investigate the types
      and frequencies of laparoscopically observed congenital anomalies of the liver.
      METHODS: We studied congenital anomalies observed laparoscopically in 1802
      consecutive patients who underwent laparoscopy from 1981 to 1994. RESULTS:
      Congenital anomalies observed laparoscopically were as follows: ape's (monkey's)
      fissure (6.8%), fissure formation with anomalous lobation (4.3%), left deviation
      of the round ligament (3.6%), high insertion of the round ligament (2.8%),
      ectopic liver and accessory lobe of the liver (0.7%), lobar fusion (0.5%),
      partial defect of the falciform ligament (0.3%), and situs inversus totalis
      (0.1%). None of these anomalies except situs inversus totalis were diagnosed by
      imaging techniques other than laparoscopy. CONCLUSION: Congenital anomalies of
      the liver are unexpectedly frequent (19.3% of patients) at laparoscopy, which
      seems to be the most useful method for finding such anomalies.

PMID- 9512278
TI  - Effect of blood on rapid urease testing of gastric mucosal biopsy specimens.
AB  - BACKGROUND: The effect of blood on rapid urease tests is uncertain. We assessed
      the effect of soaking gastric biopsy specimens in blood on the results of both
      agar gel (CLOtest) and strip (Pyloritek) rapid urease tests. METHODS: One hundred
      patients undergoing endoscopy had four adjacent biopsy specimens taken from
      normal appearing mucosa in the antrum. Two biopsies were soaked in blood for 1
      minute; one specimen was placed on a CLOtest and one on a Pyloritek. The other
      two biopsy specimens were placed on CLOtest and Pyloritek without soaking in
      blood. The same process was performed with four adjacent biopsy specimens from
      the gastric body. CLOtests were read at 1, 4, and 24 hours; Pyloritek results
      were read at 1 hour. RESULTS: The number of positive tests for the blood-soaked
      and standard biopsy specimens were comparable at all times for both rapid urease
      tests. Discordant results between the blood-soaked and standard specimens were
      seen in 17 of 400 test comparisons (4%): in 8 of these only the blood-soaked
      specimen was positive, and in 9 only the standard specimen was positive.
      CONCLUSIONS: "Contamination" of biopsy specimens with blood does not alter rapid
      urease test results.

PMID- 9512279
TI  - Enteroscopy for the initial evaluation of iron deficiency.
AB  - BACKGROUND: Occult gastrointestinal blood loss is generally investigated with
      colonoscopy and esophagogastroduodenoscopy in patients with iron-deficiency
      anemia. The aim of this study was to prospectively measure the additional
      diagnostic yield of examining the jejunum at the time of upper endoscopy in
      patients with iron-deficiency anemia. METHODS: Asymptomatic patients with newly
      diagnosed iron-deficiency anemia who had no identifiable source of blood loss at
      colonoscopy underwent standard esophagogastroduodenoscopy with the Olympus
      SIF100L enteroscope followed by overtube-assisted enteroscopy. Upper tract and
      jejunal sources of blood loss were noted. Biopsy samples from the small bowel
      were taken when a bleeding lesion was not identified. RESULTS: Thirty-one
      consecutive patients (13 men, mean age 71) with no gastrointestinal
      symptomatology were studied. Eleven patients (35%) had a bleeding source that
      required only esophagogastroduodenoscopy for identification; 8 patients (26%) had
      a source only in the jejunum; 2 patients (6%) (one with sprue) had a source in
      upper tract as well as jejunum. The enteroscopy was rated as causing minimal or
      mild discomfort in 25 of 31 patients (81%). Using Medicare reimbursement figures,
      a strategy of performing esophagogastroduodenoscopy first would have cost $656
      per patient, whereas the strategy of performing esophagogastroduodenoscopy with
      enteroscopy as the initial test in all patients costs $467 per patient.
      CONCLUSIONS: Performance of push enteroscopy along with
      esophagogastroduodenoscopy increases the diagnostic yield from 41% to 67% when
      evaluating the upper gastrointestinal tract of asymptomatic patients with iron
      deficiency anemia and, because of a lower cost, should be the preferred initial
      diagnostic test.

PMID- 9512280
TI  - Pure cut electrocautery current for sphincterotomy causes less post-procedure
      pancreatitis than blended current.
AB  - BACKGROUND: Complications after endoscopic biliary sphincterotomy occur in 8% to
      10% of patients when studied prospectively. It is not known whether the type of
      electrocautery current affects this rate. Theoretically, less edema of the
      ampulla after a pure cutting current sphincterotomy could decrease the risk of
      pancreatitis although the risk of postsphincterotomy hemorrhage might be greater.
      METHODS: One hundred seventy patients undergoing sphincterotomy were
      prospectively randomized to either a blended or pure cut current on the Valleylab
      electrosurgical unit. The settings were a blended three current at a power
      setting of 30 watts/sec for both the cut and coagulation currents or a pure cut
      current at a power setting of 30 watts/sec. The individual determining whether a
      complication occurred was blinded to the type of current used, and all patients
      were hospitalized for 24 hours post-procedure. Pancreatitis was defined as mild
      if fewer than 5 days, moderate if 5 to 14 days, and severe if more than 14 days
      of hospitalization were required. RESULTS: Indications for sphincterotomy were
      choledocholithiasis in 111 patients, sphincter of Oddi dysfunction in 36
      patients, stent placement in 15 patients, and miscellaneous in 8 patients. There
      were a total of 16 complications in 170 patients (9%); 4 (5%) were in the pure
      cut current group of 86 patients (one episode of bleeding that required
      transfusion of 4 U and three episodes of mild pancreatitis), and 12 (14%) were in
      the blended current group of 84 patients (7 mild, 2 moderate, and 1 severe
      pancreatitis; 1 case of cholangitis; and one episode of bleeding that required
      transfusion of 2 U). There were significantly fewer complications in the pure cut
      group (p < 0.05 by chi-square). CONCLUSION: The use of pure cut current is
      associated with a lower incidence of pancreatitis, the most common ERCP
      complication, than with blended current sphincterotomy. An insufficient number of
      patients were studied to comment on the relative risk of hemorrhage. However,
      because the complication of hemorrhage is much less common than pancreatitis,
      pure cut current is safer overall.

PMID- 9512281
TI  - Immunoscopy--a technique combining endoscopy and immunofluorescence for diagnosis
      of colorectal carcinoma.
AB  - BACKGROUND: Colorectal carcinoma is a common malignant disease with a high
      mortality rate. It arises most frequently in adenomas of the colorectum with
      different grades of dysplasia. Endoscopy and biopsy are among the most reliable
      diagnostic tools currently available. Diagnosis of malignancy at an early stage
      is sometimes difficult. This study reports on a new method, "immunoscopy", that
      combines endoscopy and immunofluorescent diagnostic procedures; it is the first
      reported use of locally applied fluorescein-labeled antibodies for detection of
      colorectal carcinomas. METHODS: A monoclonal antibody against carcinoembryonic
      antigen was fluorescein labeled. In phase I, formalin-fixed tissue samples, and
      in phase II, postoperative fresh tissue samples from tumorous and nontumorous
      areas of resected colorectal carcinomas were studied. After being incubated for
      10 minutes, specific fluorescence was visualized with a conventional endoscope
      whose range was increased by means of two narrow band filters. RESULTS: Because
      of high levels of autofluorescence, evaluation of immunoscopic investigations
      using formalin fixed tissue (phase I) was not carried out. Immunoscopic
      investigation with postoperative fresh tissue samples could differentiate between
      tumorous and nontumorous areas (p < 0.001). Immunoscopic results were compared
      with data from immunohistochemical investigations with anti-carcinoembryonic
      antigen on the same tissue samples. CONCLUSIONS: Immunoscopy can differentiate
      between malignant and benign mucosal areas in fresh tissue samples. The high
      sensitivity of immunoscopy could potentially make it a useful diagnostic
      complement to routine endoscopy.

PMID- 9512282
TI  - Reliability of panel-based guidelines for colonoscopy: an international
      comparison.
AB  - BACKGROUND: This study examined the reliability of explicit guidelines developed
      using the RAND-UCLA appropriateness method. METHODS: The appropriateness of over
      400 indications for colonoscopy was rated by two multispecialty expert panels
      (United States and Switzerland). A nine-point scale was used, which was
      consolidated into three categories of appropriateness: appropriate, uncertain,
      inappropriate. The distribution of appropriateness ratings between the two panels
      and the intrapanel and interpanel agreement for categories of appropriateness
      were calculated for all possible indications. Similar statistics were calculated
      for a series of 577 primary care patients referred for colonoscopy in
      Switzerland. RESULTS: Over 80% of all indications (348) could be directly
      compared. The proportions of indications classified as appropriate, uncertain, or
      inappropriate were 28.4%, 24.7%, 46.6% and 33.0%, 23.0%, 44.0% for the U.S. and
      the Swiss panels, respectively. Interpanel agreement was excellent for all the
      possible indications (kappa value: 0.75) and lower for actual cases (kappa value:
      0.51) because of lower agreement for the most frequently encountered indications.
      CONCLUSIONS: Good agreement between the two sets of criteria was found, pointing
      to the reliability of the method. Partial disagreement occurred essentially for a
      few, albeit frequently encountered, indications for use of colonoscopy in cases
      of uncomplicated lower abdominal pain or constipation.

PMID- 9512283
TI  - Prospective, randomized, controlled comparison of the use of polyethylene glycol
      electrolyte lavage solution in four-liter versus two-liter volumes and
      pretreatment with either magnesium citrate or bisacodyl for colonoscopy
      preparation.
AB  - BACKGROUND: Laxative pretreatment decreases the volume of polyethylene glycol
      electrolyte lavage solution (PEG-ELS) required for colonoscopy without
      compromising preparation quality. We compared the use of 4 L of PEG-ELS with the
      use of 2 L plus a laxative. METHODS: One hundred fifty consecutive patients (148
      men) undergoing outpatient colonoscopy were randomly selected for one of three
      preparations (Prep 1: 4 L PEG-ELS; Prep 2: 2 L PEG-ELS plus 296 mL magnesium
      citrate 1 hour prior; Prep 3: 2 L PEG-ELS plus bisacodyl 20 mg). Endoscopists
      were blinded as to the type of preparation. RESULTS: Colonoscopy times were 37,
      33, and 29.5 minutes (p = 0.02). Satisfaction scores (0 to 11) during preparation
      were 2.75, 1.84, and 2.54 (p = 0.05). Preparation times were 519, 397, and 379
      minutes (p < 0.001). Preparation satisfaction scores (0 to 10) were 6.2, 7.7, and
      7.4 (p < 0.001). Endoscopists' scores of preparation quality (1 to 10) were 7.3,
      7.8, and 8.1 (p = 0.03). Volumes of liquid stool aspirated were 181, 103, and 90
      mL (p < 0.001). Twenty-four patients receiving Prep 2 and 16 receiving Prep 3 had
      previous colonoscopy using full volume PEG-ELS; 88% who received Prep 2 and 56%
      who received Prep 3 preferred the newer preparation (p = 0.006). CONCLUSIONS: Two
      liters of PEG-ELS plus laxative improved preparation quality and patient
      satisfaction and reduced preparation time. Magnesium citrate pretreatment had
      fewer symptoms and was preferred to bisacodyl. PEG-ELS in 2 L quantities could
      reduce costs, and consideration should be given to making it available
      commercially.

PMID- 9512285
TI  - The use of a detachable mini-loop for the treatment of esophageal varices.
AB  - BACKGROUND: Endoscopic variceal ligation is facilitated by multiband ligating
      devices, but these have limitations including a fixed number of bands, occasional
      failure to firmly ligate a variceal column, and relatively high cost. We report
      the use of a mini-loop for treatment of esophageal varices. METHODS: A detachable
      nylon ring (mini-loop), maximum diameter 11 mm, passed through the accessory
      channel of a standard endoscope is opened at the rim of a transparent ligation
      chamber attached to the instrument. By suction, a varix is brought into the
      chamber, the mini-loop is maneuvered over the varix, closed, and detached.
      RESULTS: Five ligation sessions (four to seven loops per session) were performed
      in four patients with upper gastrointestinal bleeding. There were variceal
      stigmata of bleeding, but no active hemorrhage. Application of all mini-loops was
      successful and did not induce uncontrolled bleeding. Endoscopy at 1 week
      disclosed superficial ulcers at ligation sites. Post procedure epigastric pain
      occurred in one patient. CONCLUSION: Detachable mini-loop ligation of esophageal
      varices is simple and safe, and a comparison study with a multi-band ligator
      device is warranted.

PMID- 9512284
TI  - Local staging of anal and distal colorectal tumors with the magnetic resonance
      endoscope.
AB  - BACKGROUND: We prospectively assessed the feasibility and accuracy of endoscopic
      magnetic resonance (EMR) scanning in the local staging of anal and colorectal
      cancer as compared to endosonography. METHODS: Fifteen patients with biopsy
      proven anal (n = 2), rectal (n = 11), and distal colonic (n = 2) cancer underwent
      endosonography followed by EMR imaging. Scans were acquired using the magnetic
      resonance receiver coil incorporated into the tip of the non-ferromagnetic
      endoscope. Blinded to endosonography results, two radiologists interpreted the
      EMR images using the TNM system. Staging results were compared to endosonography
      in all patients and to histopathology in the 13 colorectal cases. RESULTS: EMR
      imaging, well tolerated in all patients, correlated with endosonography in 10 of
      15 and 12 of 15 cases for T- and N-staging, respectively. In the 13 colorectal
      patients with available histopathology, accuracy of EMR and of endosonography in
      T-staging was 77% and 85%, respectively; N-staging accuracy was 62% for both.
      CONCLUSIONS: For anal and distal colorectal neoplasms, EMR imaging is feasible
      and provides local staging comparable to endosonography.

PMID- 9512286
TI  - Cystic duct insertion at ampulla as a cause for acute recurrent pancreatitis.

PMID- 9512287
TI  - Intestinal ischemia complicating paroxysmal nocturnal hemoglobinuria.

PMID- 9512288
TI  - Rupture of pseudoaneurysm: a cause of delayed hemorrhage after endoscopic
      cystoenterostomy; angiographic diagnosis and treatment.

PMID- 9512289
TI  - Minimally invasive therapy for choledocholithiasis in children.

PMID- 9512290
TI  - Esophagojejunal stenting for recurrent gastric carcinoma.

PMID- 9512291
TI  - Shining the light on endoscopic research: perspectives of a "young investigator".

PMID- 9512292
TI  - Remaining questions with respect to Helicobacter pylori.

PMID- 9512293
TI  - Influence de l'age et de la lithiase biliaire sur le diametre de la voie biliare
      principale. (Influence of age and the presence of biliary stones on common bile
      duct diameter).

PMID- 9512294
TI  - Immediate recovery of psychomotor function after patient-administered nitrous
      oxide/oxygen inhalation for colonoscopy.

PMID- 9512295
TI  - Endoscopic variceal ligation in prophylaxis of first variceal bleeding in
      cirrhotic patients with high-risk esophageal varices.

PMID- 9512297
TI  - Pulse oximetry: training and knowledge.

PMID- 9512296
TI  - Premedication for gastrointestinal endoscopy is a rare practice in Finland: a
      nationwide survey.

PMID- 9512298
TI  - Recommendations for pain management during colonoscopy.

PMID- 9512299
TI  - Colonoscopy and missed colon cancers.

PMID- 9512300
TI  - Large hyperplastic polyps of the right colon.

PMID- 9512301
TI  - Lateral internal sphincterotomy remains the treatment of choice for anal fissures
      that fail conservative therapy.

PMID- 9512302
TI  - Demonstration of pericardial fluid on endoscopic ultrasound.

PMID- 9512303
TI  - Quantification of cerebrospinal fluid proteins in children by high-resolution
      agarose gel electrophoresis.
AB  - Physiologic alterations in cerebrospinal fluid proteins occur inter alia with
      aging. Agarose gel electrophoresis discriminates many cerebrospinal fluid
      proteins and in addition quantifies concentration alterations. This study aimed
      to investigate the time course of these alterations in children and to establish
      normative values for cerebrospinal fluid protein properties. In 202 children
      without diseases known to alter cerebrospinal fluid, normative protein properties
      were quantified using nephelometry, ultrafiltration, high-resolution
      electrophoresis, and Gaussian curve fit densitometry. Total protein and protein
      concentrations (albumin and gamma-globulins) decreased from birth until 7 months
      age, and, from then on, increased slightly (transthyretin, albumin, and alpha2
      proteins) or strongly (gamma-globulins). Protein proportions (transthyretin and
      transferrin) increased until about 3 years of age and decreased from then on.
      These normative values for children as quantified by high-resolution agarose gel
      electrophoresis are presented in a significance-structured percentile table. The
      time courses of these cerebrospinal fluid properties reflect physiologic
      alterations of the blood-brain barrier function during childhood.

PMID- 9512304
TI  - Immunocytochemical development of transferrin and ferritin immunoreactivity in
      the human pons and cerebellum.
AB  - The distribution and development of transferrin-positive cells in the pons and
      cerebellum of human fetuses to adults were examined immunohistochemically,
      compared with those of ferritin-positive cells. Transferrin was present in
      oligodendrocytes, astrocytes, and neurons. Transferrin-positive neurons appeared
      at 18 weeks of gestation in Purkinje cells and the pontine reticular formation.
      In the pontine nuclei, transferrin-positive neurons appeared at 22 weeks of
      gestation. On the other hand, transferrin-positive glia also appeared at 18 weeks
      of gestation in the reticular formation, and at 24 weeks of gestation in the
      cerebellar white matter and pontine nuclei. Transferrin-positive glia and cells
      appeared earlier in the reticular formation of the pons than ferritin, but the
      order of its appearance was similar to that of ferritin and myelination. Because
      iron is involved in the syntheses and functions of dopamine, serotonin, and gamma
      aminobutyric acid (GABA), transferrin may be carried for various iron uses from
      an early fetal stage.

PMID- 9512305
TI  - Psychosocial adjustment of children with spina bifida.
AB  - It was the aim of the present prospective study to investigate the influence of
      age, sex, intellectual function, and school type as well as of hydrocephalus, the
      level of lesion, and of the degree of handicap on the psychosocial adjustment of
      children with spina bifida. Seventy-five patients with spina bifida, aged 6 to 16
      years were assessed concerning their psychosocial adjustment and their
      intellectual function by use of standardized instruments. The findings were
      compared with those of nondisabled controls, matched for age and sex. Children
      with spina bifida showed a tendency to be at an increased risk for psychosocial
      maladjustment. Influencing factors were age, sex, and the degree of handicap.
      Twelve- to 16-year-old boys and girls displayed significant adjustment problems
      in specific areas in comparison with their controls. There was a tendency for
      children with spina bifida to be attending inappropriate school types according
      to their intellectual abilities. Perhaps the most striking finding of our study
      was that children with spina bifida who attended a school for disabled children,
      even though it might be an IQ-appropriate setting, had a higher rate of
      psychosocial maladjustment than the disabled children in mainstream schools.

PMID- 9512306
TI  - Hand and foot growth failure in Rett syndrome.
AB  - Growth failure is a major aspect of the developmental arrest in Rett syndrome.
      Small hands and feet have been reported anecdotally, but the pattern of hand and
      foot growth has not been studied rigorously. The aims of this study were to
      characterize the hand and foot growth of 28 girls with Rett syndrome and to
      examine the relationship between their hand or foot size and height. Median hand
      length deviated to the 5th percentile at 11 years of age whereas median foot
      length and height deviated below the 5th percentile at 5.5 years of age. After
      adjusting for height-age, a greater proportion of foot lengths than hand lengths
      was less than the 50th percentile. In conclusion, the rate of hand and foot
      growth of girls with Rett syndrome is slower than that of the normal female.
      Moreover, the rate of deceleration of foot, but not hand, growth relative to
      height growth is greater. Thus, many girls with Rett syndrome have "small" feet,
      but not hands, for their height.

PMID- 9512307
TI  - Nova Scotia Niemann-Pick disease (type D): clinical study of 20 cases.
AB  - Patients with Niemann-Pick type D have been traced to a single Acadian ancestor
      in Nova Scotia. The objective of this study was to describe the clinical course.
      A cohort of children with Niemann-Pick type D was identified by chart review.
      Some children were seen and a telephone interview with the remaining parents was
      conducted. Twenty children with Niemann-Pick type D were identified. The female
      to male ratio was 2:1. Five children had severe neonatal jaundice. Early
      milestones were normal in the majority. Neurologic symptoms generally developed
      between 5 and 10 years of age with a mean age of 7.2 years at diagnosis. Seizures
      developed in all between 4.5 and 16 years of age (mean, 10.5 yr), and were
      followed by significant physical and mental deterioration. The age at death
      ranged between 11 and 22.5 years (mean, 14.8 yr). In 61%, bronchopneumonia was
      the cause of death. There is significant variability in the presentation and
      clinical course of Niemann-Pick type D.

PMID- 9512308
TI  - Intravenous immunoglobulin treatment of children with autism.
AB  - Since autism has been associated with immunologic abnormalities suggesting an
      autoimmune cause of autistic symptoms in a subset of patients, this study was
      undertaken to investigate whether intravenous immunoglobulin (i.v.Ig) would
      improve autistic symptoms. Ten autistic children with immunologic abnormalities,
      demonstrated on blood tests, were enrolled in this study. Their ages ranged from
      4 to 17 years, with two girls and eight boys. Eight children (1 female and 7
      male) historically had undergone autistic regression. Intravenous immunoglobulin,
      200 to 400 mg/kg, was administered every 6 weeks for an intended treatment
      program of four infusions. In five children, there was no detectable change in
      behavior during the treatment program. In four children, there was a mild
      improvement noted in attention span and hyperactivity. In none of these children
      did the parents feel that the improvement was sufficient to warrant further
      continuation of the infusions beyond the termination of the program. Only in one
      child was there a very significant improvement, with almost total amelioration of
      autistic symptoms over the time period of the four infusions. Once the treatment
      program was completed, this child gradually deteriorated over a 5-month time
      period and fully reverted to his previous autistic state. In this treatment
      program, five children had no response to intravenous immunoglobulin. In the four
      children who showed mild improvements, those improvements may simply have been
      due to nonspecific effects of physician intervention and parental expectation
      (ie, placebo effect). However, in one child there was a very significant
      amelioration of autistic symptoms. There were no distinguishing historic or
      laboratory features in this child who improved. Given a positive response rate of
      only 10% in this study, along with the high economic costs of the immunologic
      evaluations and the intravenous immunoglobulin treatments, the use of intravenous
      immunoglobulin to treat autistic children should be undertaken only with great
      caution, and only under formal research protocols.

PMID- 9512309
TI  - Syndromic diagnosis in para-infectious neurologic disease: varicella ataxic
      syndrome.

PMID- 9512310
TI  - An unusual behavior of brainstem ependymoma.

PMID- 9512311
TI  - Segregation analysis in typical absence epilepsy.

PMID- 9512312
TI  - A urea cycle defect presenting as acute cerebellar ataxia in a 3-year-old girl.

PMID- 9512313
TI  - A novel missense mutation (837T-->C) in the phosphoglycerate kinase gene of a
      patient with a myopathic form of phosphoglycerate kinase deficiency.

PMID- 9512314
TI  - Melatonin treatment of chronic sleep disorders.

PMID- 9512315
TI  - A survey of etiological mechanisms and therapy of preterm labor.

PMID- 9512316
TI  - The influence of amniotic fluid on prostaglandin synthesis and metabolism in
      human fetal membranes.
AB  - OBJECTIVE: To investigate the effect of amniotic fluid on prostaglandin synthesis
      and metabolism in the fetal membranes. DESIGN: A cell culture study of amnion and
      chorion obtained at elective cesarean section incubated with amniotic fluid
      collected following either spontaneous labor and delivery, or elective cesarean
      section. SUBJECTS: Forty-eight pregnant women at 3742 weeks gestation: 24 in
      spontaneous labor and 24 delivered by elective cesarean section. RESULTS:
      Significantly more PGE2 and PGF2alpha were produced by amnion and chorion treated
      with amniotic fluid from spontaneous labor compared with elective cesarean
      section. Spontaneous labor amniotic fluid favors PGE2 and PGFM production by
      amnion and chorion respectively; while elective section fluid stimulates PGE2
      synthesis by both tissues (reflected as PGEM in chorion). Amniotic fluid, from
      either spontaneous labor or elective section, had no effect on the metabolism of
      exogenous PGE2 or PGF2alpha by chorion cells. CONCLUSION: Spontaneous labor is
      associated with the presence of a substance in amniotic fluid which facilitates
      prostaglandin synthesis in the fetal membranes, but which is without effect on
      prostaglandin metabolism.

PMID- 9512317
TI  - Amniocentesis before the 15th gestational week in single and twin gestations
      complications and quality of genetic analysis.
AB  - BACKGROUND: Early amniocentesis has been claimed to confer a higher risk of fetal
      loss than standard amniocentesis after the 15th gestational week. Our experience
      of early amniocentesis in single and twin gestations from 1990 - 1995 is
      presented with 99.3% follow-up. METHODS: Amniocentesis was performed between 11
      gestational weeks + 5 days and 14 gestational weeks + 6 days. RESULTS: In 1646
      pregnancies 1678 amniocenteses were performed. Thirty-two reamniocenteses were
      done, 17 due to amniocyte culture failure and 15 due to failure to obtain
      sufficient amount of amniotic fluid on the first occasion. After puncture 1.49%
      (25/1678) suffered a spontaneous abortion. Twenty twin pregnancies were included.
      One spontaneous abortion was noted in this group, as well as three cases where
      one fetus was normal and the other had a severe defect. Selective abortions were
      performed without complications. CONCLUSIONS: The difference of postprocedure
      fetal loss in our population between early and standard amniocentesis is 0.8%. A
      comparison of postprocedure losses is not appropriate when amniocenteses are
      performed at a different gestational age, as spontaneous loss decreases with
      increased gestational age. Our results compare well with the only randomized
      study between early and standard amniocentesis where the fetal loss after early
      amniocentesis is similar to that in standard amniocentesis.

PMID- 9512318
TI  - Serum levels of human placental lactogen, pregnancy-associated plasma protein A
      and endometrial secretory protein PP14 in first trimester of diabetic pregnancy.
AB  - OBJECTIVE: To study maternal serum levels of human placental lactogen (hPL),
      pregnancy-associated plasma protein A (PAPP-A) and endometrial secretory protein
      PP14 (PP14) in first trimester of diabetic pregnancy. METHODS: Seventy-nine
      insulin-dependent diabetic women and 93 normal pregnant women had a venous blood
      sample drawn in weeks 8-14, ultrasound age. Serum levels were measured by
      radioimmunoassays and expressed in multiples of the median serum value in normal
      pregnancy at that ultrasound age. RESULTS: Levels of hPL were significantly lower
      in diabetic mothers than in controls, z'= -5.502, p<0.00001. Levels of PAPP-A
      were also significantly lower, z' =2.263, p=0.024, but were significantly less
      depressed than those of hPL, z'=2.41, p=0.015. The PP14 levels did not deviate
      from normal. CONCLUSION: In first trimester of diabetic pregnancy there appears
      to be both a more general depression of trophoblast function, and also a specific
      depression of the hPL release.

PMID- 9512319
TI  - Smoking habits among pregnant women in Norway 1994-95.
AB  - AIMS: To investigate the smoking prevalence the last three months before
      pregnancy and at 18 weeks of gestation among women in Norway and to evaluate the
      impact of pre-pregnancy smoking habits, maternal age, level of education, civil
      status and parity on smoking cessation. MATERIAL AND METHODS: A prospective,
      multicenter survey. The study population included 4 766 pregnant women who
      attended a routine ultrasound examination at 18 weeks of pregnancy in six
      Norwegian hospitals during the period from September 1994 to March 1995. Smoking
      habits before and during pregnancy were recorded. RESULTS: The point prevalence
      of self-reported daily smoking among the women three months before the pregnancy
      was 34%. At 18 weeks of pregnancy, 21% of the women reported smoking daily
      (p<0.001). A multiple logistic regression analysis revealed that a low number of
      cigarettes smoked per day during the last three months before pregnancy was the
      best predictor for smoking cessation. Educational level, maternal age, parity and
      civil status were also statistically significant contributors to smoking
      cessation. Eighty percent of the women who were unable to stop smoking, reported
      a reduction in cigarette consumption. The mean number of cigarettes per day was
      reduced from 13.9 before pregnancy to 7.3 at 18 weeks of pregnancy (p<0.001).
      CONCLUSION: In a national survey, 21% of the pregnant women reported smoking
      daily in the second trimester. Thirty-eight percent of the women who were daily
      smokers before the pregnancy stopped smoking in early pregnancy. A low cigarette
      consumption prior to the pregnancy was the best predictor for smoking cessation.

PMID- 9512320
TI  - Soluble fibrin in plasma as a sign of activated coagulation in patients with
      pregnancy complications.
AB  - BACKGROUND: Disseminated intravascular coagulation (DIC) is a frequently observed
      complication in pregnant women. The laboratory diagnosis of DIC is difficult but
      the development in the detection of circulating soluble fibrin has improved the
      possibility. METHODS: A number of pregnant women (n= 175) with obstetric
      complications e.g. preeclampsia, hypertension, intrauterine growth retardation
      (IUGR) and intrahepatic cholestasis was examined for plasma soluble fibrin and
      subjected to some routine hemostatic tests, mainly during the third trimester of
      pregnancy. RESULTS: Of these patients, 57 of 175 (33%) had an elevated
      concentration of soluble fibrin (above 23 nmol/L) as compared with a healthy
      group of women sampled in the third trimester. Eighteen patients (10%) had highly
      increased levels, above 100 nmol/L. In comparison, none of the 23 healthy,
      pregnant women investigated had a value above 40 nmol/L. CONCLUSIONS: Hemostatic
      abnormalities, including increased concentrations of soluble fibrin, are quite
      frequently observed in women with obstetric complications, most likely as a sign
      of a systemic activation of coagulation. Although a higher concentration of
      plasma soluble fibrin was observed in many of the women, no clear correlation to
      the outcome of the pregnancy was obtained. Whether or not plasma soluble fibrin
      is of any value, either diagnostically or the treatment of patients with
      pregnancy complications, remains to be shown.

PMID- 9512321
TI  - The cumulative incidence of venous thromboembolism during pregnancy and
      puerperium--an 11 year Danish population-based study of 63,300 pregnancies.
AB  - OBJECTIVES: The aim of the study was to estimate the cumulative incidence of
      venous thromboembolism during pregnancy and the puerperium. METHODS: All
      diagnoses concerning venous thromboembolism in the Hospital Discharge Registry
      from a Danish County in women less than 49 years of age from 1984 to 1994 were
      included. The number of deliveries in the County during this period was obtained
      from The Medical Registry of Birth. RESULTS: The cumulative incidence of venous
      thromboembolism during pregnancy and puerperium was 0.85 (95% CI: 0.64-1.11) per
      1000 deliveries. The cumulative incidence was 0.49 (95% CI: 0.28-04).80) in 1984
      89 but increased to 1.23 (95% CI: 0.87-1.69) after the introduction of
      ultrasound. CONCLUSION: The risk of diagnosed venous thromboembolism is low but
      estimates of the incidence are probably procedure dependent.

PMID- 9512322
TI  - Reduction of serum citrulline levels in women at term toward the day of labor
      onset.
AB  - OBJECTIVE: To test the hypothesis that labor onset could be the result of a
      reduced release of nitric oxide (NO). STUDY DESIGN: Out of 91 consecutive healthy
      nulliparous women at term serum citrulline (Cit) and arginine (Arg) levels were
      measured at least twice in 37 subjects, by the means of HPLC with fluorometric
      detection. Twenty cases underwent a spontaneous onset of labor (group A) while in
      17 cases labor was induced (group B) because of pregnancy prolongation or
      amniotic fluid reduction. RESULTS: Cit and Arg levels were unaffected by the
      gestational age. In group A, Cit levels undergo a progressive decrease toward the
      day of labor (from 32.9+/-4.7 microM/L the day - 18,-5 to 27.7+/-7.8 the day 
      4,0; p=0.012) whilst they remained stable in group B (from 33.3+/-7.7 to 34.2+/
      9.2). No significant changes were observed in Arg levels. Cit/Arg ratio remained
      stable in group A whereas it showed a trend to increase in group B. CONCLUSION:
      These data indirectly suggest a reduced release of NO toward term. This
      phenomenon could play a permissive role in the spontaneous onset of labor of
      healthy nulliparous women.

PMID- 9512323
TI  - Randomized comparison of rectal misoprostol with Syntometrine for management of
      third stage of labor.
AB  - BACKGROUND: The search for an effective, easily stored, affordable uterotonic
      agent in preventing postpartum hemorrhage is of importance, especially in the
      developing world. The objective of this study was to randomly compare the
      effectiveness of rectal misoprostol with Syntometrine in the management of the
      third stage of labor. METHODS: Four hundred and ninety-one low risk women in
      labor were randomly allocated to receive either misoprostol 400 microgram
      rectally or Syntometrine 1 ampuole intramuscularly, and postpartum blood loss was
      estimated as the principal end point. Comparisons were by the chi-square test or
      Fisher's test and relative risks with 95% confidence intervals for categorical
      data, and the Mann-Whitney test for ranked continuous variables. RESULTS: The
      baseline characteristics in terms of hemoglobin estimation in antenatal clinic,
      mean age, parity, and duration of labor in the 250 patients who received
      Syntometrine and 241 patients who received misoprostol were similar. However,
      there was a significant difference in the pre-delivery blood pressure of the two
      groups because of the non-protocol exclusion of women with elevated blood
      pressure allocated to receive Syntometrine. Duration of third stage of labor,
      blood loss postpartum and hemoglobin estimation post partum were all similar.
      Postpartum diastolic hypertension was more common in the Syntometrine group (p=
      0.002). No other apparent side effect was noted in either group. CONCLUSION:
      Misoprostol rectally for management of the third stage of labor merits further
      investigation.

PMID- 9512324
TI  - Umbilical cord blood acid-base values in uncomplicated term vaginal breech
      deliveries.
AB  - BACKGROUND: This prospective study was conducted to compare the umbilical cord
      blood acid-base values of uncomplicated, assisted, vaginal-breech-delivery term
      neonates with those of uncomplicated, cephalic-vaginal delivery term neonates and
      to determine whether a different metabolic status should be expected in neonates
      born by way of uncomplicated vaginal breech delivery. METHODS: Umbilical cord
      artery and vein blood samples were obtained from 30 term neonates with frank or
      complete breech presentations who were born by uncomplicated assisted vaginal
      breech delivery. All these neonates had an Apgar score of >7 at 5 min and an
      uneventful neonatal course (study group). For each neonate in the study group the
      two consecutive term neonates who were delivered by uncomplicated cephalic
      spontaneous vaginal delivery, and had uneventful neonatal courses, served as
      controls (control group). RESULTS: The umbilical cord artery blood pH and pO2
      were significantly lower (p<0.001 and <0.01, respectively) and the pCO2 was
      significantly higher (p<0.001) in newborns of the study group, compared to the
      controls. The umbilical cord vein blood pH was significantly lower (p<0.01), and
      the pCO2 significantly higher (p<0.01) in the study group. CONCLUSIONS: The
      umbilical cord blood acid-base values of uncomplicated, vaginal-breech-delivery
      term neonates differ significantly from those of uncomplicated, cephalic-vaginal
      delivery neonates. These differences may represent a greater degree of acute cord
      compression that reflects the different mechanisms of labor in vaginal breech
      delivery.

PMID- 9512325
TI  - Emergency hysterectomy in modern obstetric practice. Changing clinical
      perspective in time.
AB  - OBJECTIVE: Emergency hysterectomy in obstetric practice is generally performed in
      the setting of life-threatening hemorrhage. A retrospective review based on
      hospital data of 67 patients undergoing emergency peripartum hysterectomy over 10
      years was undertaken. METHODS: Comparison of two different time periods regarding
      the incidence and the indications of obstetric hysterectomies was made. RESULTS:
      The number of patients with hysterectomy in the first 5 years of the study period
      (1985-1989) was 43 and during the last 5 years (1990-1994) it was 24. The
      incidence of hysterectomy during 1985-1989 was 1 in 2495 deliveries and the most
      common indication for hysterectomy was uterine atony (42%) followed by placenta
      accreta (25.5%) and uterine rupture (21%). On the other hand, the incidence of
      hysterectomy during 1990-1994 was 1 in 4228 deliveries and the ranking of
      indications of hysterectomy was slightly different from group 1 as mostly
      placenta accreta (41.7%) followed by uterine atony (29.2%). The maternal
      mortality rate was 4.5% in this series. CONCLUSION: This study showed that over
      the last decade the incidence of emergency hysterectomy in obstetric practice has
      declined in our clinic due to availability of high standard obstetric care and
      more liberal use of cesarean section at risk deliveries, better controlled use of
      oxytocin and internal iliac artery ligation.

PMID- 9512326
TI  - Incidence of sex chromosome abnormalities in spermatozoa from patients entering
      an IVF or ICSI protocol.
AB  - OBJECTIVE: The objective of this study was the determination of sex chromosome
      aneuploidy frequency in spermatozoa from patients included in an in vitro
      fertilization (IVF) or intra cytoplasmic sperm injection (ICSI) protocol.
      METHODS: Spermatozoa from nineteen patients, including patients with normal
      seminal parameters according to World Health Organization (WHO) criteria and
      patients exhibiting abnormal seminal parameters, were analyzed by dual color
      fluorescence in situ hybridization (FISH) for aneuploidies of the X and Y
      chromosomes. Our technique, using only probes for sex chromosomes and not for
      autosomes, does not discriminate between hyperhaploid and diploid sperm nuclei.
      The results were analyzed in two different ways: in relation to the semen status,
      denoted normal or abnormal and with regard to the ability of the sperm to
      fertilize oocytes when IVF or ICSI was performed. RESULTS: Abnormal semen showed
      a significant increase in the overall rate of sperm nuclei with XY, XX and YY sex
      chromosome complements, 1.59% compared to normal semen, 0.78% (p<0.02). Semen
      shown to be able to fertilize oocytes only by ICSI showed a higher incidence of
      XY-bearing spermatozoa, 1.26%, compared to semen able to fertilize oocytes by
      conventional IVF, 0.37% (p<0.001). The incidence of XX-or YY-bearing sperm nuclei
      was also significantly elevated in the ICSI group (0.25% XX, 0.50% YY) (p<0.02)
      as compared to the IVF group (0.06% XX, 0.16% YY). CONCLUSIONS: We concluded that
      infertile men requiring ICSI treatment showed a higher incidence of sex
      chromosome aneuploidy, due to meiosis I and II nondisjunction, in their
      spermatozoa as compared to men requiring IVF for reasons of predominantly female
      infertility.

PMID- 9512327
TI  - A halt in the secular trend towards earlier menarche in Denmark.
AB  - BACKGROUND: A halt in the decrease of menarcheal age has been reported in some
      countries but has not been documented in Denmark. METHODS: The entire population
      of schoolgirls, attending grades 5 through 10 (n=979), in a particular region of
      Denmark was investigated by the status quo method in 1996. Similar investigations
      had been made in the same region and by the same method in 1966 and 1983. Mean
      age and standard deviation were estimated by probit analysis. RESULT: Mean age
      was 13.00 years (s.e.=0.080; s.d. = 1.15) and almost identical with the mean age
      in 1983 (13.03 years), but significantly different from the mean age in 1966
      (13.40 years). CONCLUSION: The results indicate a halt in the secular trend
      towards earlier menarche in the region at some time between 1966 and 1983.

PMID- 9512329
TI  - Oral contraceptive use in relation to smoking.
AB  - BACKGROUND: Use of OC simultaneous with smoking in older women remains a concern
      for prescribing physicians, in light of current guidelines for OC use and
      evidence from recent studies about risks and benefits of different OC agents. It
      is useful to look at prevalence of OC use simultaneously with smoking after age
      of 35, as an indication of the effectiveness of these guidelines. METHODS: Survey
      of OC use in relation to smoking on a representative sample of 1138 urban women
      aged 40-54, from Geneva, Switzerland. History of exposure to both OC and smoking
      is analyzed up to the age of 40. RESULTS: Seventy-six percent of women had ever
      used OC, and 49% had ever smoked by age 40. Fifty-four percent of women reported
      OC exposure simultaneous to smoking at some time, and simultaneous exposure
      accounted for 48% of woman-years of use. But simultaneous use decreased with age,
      such that simultaneous users during age 36-40 accounted for 37% of OC users
      during that age period, and for only 13% of all ever OC users. Similarly, woman
      years of OC use simultaneous with smoking fell after age 25, and woman-years
      during age 36-40 accounted for 36% of woman-years during that age period, such
      that only 5% of woman-years of OC use overall. CONCLUSIONS: OC use simultaneous
      with smoking after age 35 is not typical. Results suggest that a physician today
      may prescribe a type of OC that fits a young woman's current risk profile,
      confident of being able to change OC use or smoking by the time the woman enters
      an older risk profile. Prescribing OC to a young smoker does not generally lead
      to simultaneous exposure at a later age.

PMID- 9512328
TI  - Combined laboratory and diary method for objective assessment of menstrual blood
      loss.
AB  - BACKGROUND: To develop an objective measurement system for menstrual blood loss
      applicable in clinical practice. METHODS: One hundred and fifty-six patients were
      enrolled in a randomized trial of the treatment of menorrhagia in all five
      gynecology departments of the university teaching hospitals in Finland.
      Correlation between venous blood hemoglobin concentration (Hb) and absorbance at
      564 nm (A564) was investigated in experiments with blood samples. Amount of
      collected menstrual blood and menstrual diary data were analyzed. RESULT: Hb
      concentration and A564 of the blood were linearly correlated (r=0.99). One
      hundred and fifty-four women (99%) returned used sanitary protection and
      menstrual diaries. On average, 12% (range 0-57%) of menstrual blood was lost
      during collection. The median amount of blood recovered from sanitary protection
      was 89 ml (range 14-724 ml), with 58% (n=90) of the women exceeding 80 ml per
      cycle. When the spilled blood was taken into account, the corresponding figures
      were 104 ml (range 15-724 ml) and 66% (n= 101). CONCLUSIONS: The
      spectrophotometric measurement of venous blood in the conventional alkaline
      hematin method can be replaced by measurement of Hb concentration. All blood
      incompletely collected should be recorded. Objective measurement of menstrual
      blood loss can be applied in routine clinical practice.

PMID- 9512330
TI  - Quality of care in abortion services in Finland.
AB  - BACKGROUND: The aim of this study was to describe the quality of abortion
      services and women's experiences with the care they had received during their
      abortion. METHODS: A population-based postal survey of 3000 randomly selected 18
      44-year old Finnish women in 1994. The response rate was 74% (n=2189). The
      following were used as indicators of quality of services: referral problems, loss
      of follow up, adequacy of counseling, and satisfaction with treatment. RESULTS:
      Fifteen percent (n=320) of the respondents had experienced at least one abortion.
      After adjusting for age, women who had an abortion were more likely to come from
      the lower social class, to be divorced, widowed, or in a nonmarital relationship,
      and to have had previous pregnancies. Fifty-two percent reported not using any
      contraceptive method when getting pregnant. Altogether 6% reported referral
      problems and 8% did not have post-abortion follow-up. Twenty-five percent would
      have preferred more discussion with a physician or a nurse before the abortion
      and 30% after it. Psychological effects of abortion was the most often mentioned
      subject upon which they needed discussion. The need for discussion was not
      influenced by the length of time lapsed since the abortion. The satisfaction with
      treatment increased from 69% (abortion >10 years ago) to 82% (abortion <5 years
      ago). Dissatisfaction was related to need for more discussion and the abortion
      having been performed in a central hospital. CONCLUSION: The overall quality of
      abortion care was good but there is still a need for improvement, especially in
      the communication and human part of the care.

PMID- 9512331
TI  - Sonographic evaluation of the myomectomy 'scars'.
AB  - BACKGROUND: The evolution of myomectomy 'scars' has not been reported. This
      prospective study was carried out to determine the evolution of the myomectomy
      'scars' following conventional open myomectomy. METHODS: Ten patients admitted
      for myomectomy were recruited. The sizes of the leiomyomata were determined with
      ultrasonography. Serial sonographic examinations were performed following the
      open myomectomy so as to determine the morphology and volume of the scars. The
      volumes of the uterus were also measured to document the postoperative remodeling
      of the uterus. RESULTS: The myomectomy 'scars' were represented by an area with
      mixed echogenic echoes in the immediate postoperative period. In one month, their
      volumes decreased to less than 5% of the preoperative volumes and were reduced to
      vague areas marked by short echogenic lines at 6 months. Most of the remodeling
      of the uterus occurred in the first month postoperatively. CONCLUSIONS: The mixed
      echogenic areas probably represented the approximated myometrial walls of the
      leiomyomata. Detection of such in postoperative sonography should not cause undue
      alarm.

PMID- 9512332
TI  - Present state of diagnostics and therapy in female urinary incontinence.
AB  - OBJECTIVE: To determine the present state of urogynecological diagnostics,
      therapy and follow-up in the Departments of Gynecology and Obstetrics in Austria.
      DESIGN: We sent questionnaires to all Departments of Gynecology and Obstetrics in
      Austria. The anonymous questionnaire consisted of 25 multiple choice questions.
      It was possible to choose one ore more answers by ticking applicable boxes with
      the casual option to give some additional information in form of free text.
      RESULTS: Fifty-eight departments (58%) returned their questionnaires completely
      answered indicating interest in quality management in medicine. The most
      remarkable discrepancy was found between the interrogated people's estimation of
      the expressiveness of examination techniques and the actual use of such
      techniques. CONCLUSION: We regard the results of this survey as a basis for
      further quality management strategies in the field of urogynecology in Austria.

PMID- 9512333
TI  - Incidence of cervical intraepithelial neoplasia grade III, and cancer of the
      cervix uteri following a negative Pap-smear in an opportunistic screening.
AB  - BACKGROUND: To investigate the influence of screening history on the diagnosis of
      cervical intraepithelial neoplasia grade three (CIN III) and cervical cancer in
      an opportunistic screening program. DESIGN: Follow-up study of women with a
      negative Pap-smear at entry. MATERIALS: Records from 41212 women pertaining to
      cervical specimens in the Pathology Registry of the University Hospital in
      Tromso. RESULTS: During the 175,673 person-years (pyr) of observation, 396
      incident cases (379 of CIN III and 17 of cervical cancer) were identified. The
      age specific incidence rate was highest among women who were 25 to 29 years old
      (396 per 100,000 pyr). A Poisson multiple regression model yielded statistically
      significant positive associations between time since last negative Pap-smear and
      the incidence of CIN III and cervical cancer. Most CIN III cases were diagnosed
      subsequently to a CIN I or CIN II diagnosis. Including only women with a CIN III
      diagnosis directly after a negative Pap-smear in the analyses revealed that women
      with less than two years (Relative rate (RR)= 1.O; 95% CI 0.7-1.4) and three
      years (RR=0.8; 95% CI 0.4-1.4) since their last negative Pap-smear were not at an
      increased risk compared with the women with a negative Pap-smear within the last
      year. Women with three or more years since their last negative Pap-smear were at
      an increased risk (RR=1.3; 95% CI 0.6 3.2) for CIN III. No meaningful association
      between number of negative specimens and the risk of CIN III was revealed.
      CONCLUSION: This study indicates that time since last negative Pap-smear does,
      while number of such does not, influence the risk of CIN III and cervical cancer
      in an opportunistic screening.

PMID- 9512334
TI  - Platin-based chemotherapy and salvage surgery in recurrent ovarian cancer
      following negative second-look laparotomy.
AB  - AIM: To evaluate the role of platin-based chemotherapy followed by salvage
      surgery in patients with recurrent ovarian cancer after negative second-look
      laparotomy. METHODS: A retrospective chart review was conducted on 38 patients
      with recurrent ovarian cancer after a pathologic complete response to first-line
      chemotherapy. After diagnosis of recurrence all patients underwent retreatment
      with platin-based chemotherapy followed by radical salvage surgery. RESULTS:
      Recurrent disease was diagnosed at a median interval of 22 months after second
      look surgery. All patients had complete surgical debulking with no macroscopic
      tumor at the completion of the surgical procedure. Eight patients (21%) required
      an intestinal resection but no colostomy was performed. Two operative deaths
      occurred (5%). Twenty-two patients (58%) experienced a second recurrence after
      salvage surgery The median survival time for all patients after diagnosis of
      recurrent disease was 29 months (range 6-96 months), with nine patients (25%)
      surviving more than three years. Survival time after diagnosis of recurrence was
      not significantly related either to known prognostic factors of ovarian cancer or
      to the length of the clinical remission time. CONCLUSION: Retreatment with platin
      based chemotherapy followed by salvage surgery should be offered to recurrent
      ovarian cancer patients and would appear to prolong survival in a highly selected
      group of patients.

PMID- 9512335
TI  - Iatrogenic brain injury during emergency cesarean section.

PMID- 9512337
TI  - Excessive fetomaternal transfusion and marked sinusoidal fetal heart rate.

PMID- 9512336
TI  - In utero adrenal hemorrhage: clinical and imaging findings.

PMID- 9512338
TI  - Increased serum level of inhibin causes amenorrhea in a granulosa cell tumor
      patient.

PMID- 9512339
TI  - Steroid production and gonadotropin sensitivity in vitro of a human hilus cell
      tumor.

PMID- 9512340
TI  - Epithelioid leiomyosarcoma of the uterine cervix.

PMID- 9512341
TI  - Transgene expression in Xenopus rods.
AB  - The photoreceptors of the vertebrate retina express a large number of proteins
      that are involved in the process of light transduction. These genes appear to be
      coordinately regulated at the level of transcription, with rod- and cone-specific
      isoforms (J. Hurley (1992) J. Bioenerg. Biomembr. 24, 219-226). The mechanisms
      that regulate gene expression in a rod/cone-specific fashion have been difficult
      to address using traditional approaches and remain unknown. Regulation of the
      phototransduction proteins is medically important, since mutations in several of
      them cause retinal degeneration (P. Rosenfeld and T. Dryja (1995) in: Molecular
      Genetics of Ocular Disease (J.L. Wiggs, Ed.), pp. 99-126, Wiley-Liss Inc.). An
      experimental system for rapidly producing retinas expressing a desired mutant
      would greatly facilitate investigations of retinal degeneration. We report here
      that transgenic frog embryos (K. Kroll and E. Amaya (1996) Development 122, 3173
      3183) can be used to study cell-specific expression in the retina. We have used a
      5.5 kb 5' upstream fragment from the Xenopus principal rod opsin gene (S. Batni
      et al. (1996) J. Biol. Chem. 271, 3179-3186) controlling a reporter gene, green
      fluorescent protein (GFP), to produce numerous independent transgenic Xenopus. We
      find that this construct drives expression only in the retina and pineal, which
      is apparent by 4 days post-nuclear injection. These are the first results using
      transgenic Xenopus for retinal promoter analysis and the potential for the
      expression in rod photoreceptors of proteins with dominant phenotypes.

PMID- 9512342
TI  - Site-directed mutagenesis of the Proteus mirabilis glutathione transferase B1-1 G
      site.
AB  - In order to investigate the roles of near N-terminus Tyr, Cys, and Ser residues
      in the activity of bacterial glutathione transferase (GSTB1-1) site-directed
      mutagenesis was used to replace the following residues: Tyr-4, Tyr-5, Ser-9, Cys
      10, Ser-11, and Ser-13. The results presented here show that, unlike all other
      alpha, mu, pi, theta and sigma classes of glutathione transferases so far
      investigated, GSTB1-1 does not utilise any Tyr, Ser or Cys residue to activate
      glutathione. These results also suggest that the bacterial glutathione
      transferases may require classification into their own class.

PMID- 9512343
TI  - Protein synthesis is involved in the modulation of the level of the
      phosphoenolpyruvate carboxykinase mRNA by changes in cell volume in isolated rat
      hepatocytes.
AB  - The mechanism of action of hydration state was studied on phosphoenolpyruvate
      carboxykinase (PCK) gene expression in isolated rat hepatocytes. Hypoosmolarity
      decreased the level of the PCK mRNA after a lag period of about 60 min. The
      decreasing effect of hypoosmolarity was totally blocked by inhibitors of both
      protein synthesis and gene transcription. Moreover, hypoosmolarity specifically
      increased the synthesis of a 45000 Mr protein, which decreased in the presence of
      inhibitors of transcription. A close relationship between the synthesis of the
      45000 Mr protein and the decrease in the PCK mRNA level was observed, suggesting
      that this protein might potentially be involved in the regulation of the level of
      the PCK mRNA by cell swelling.

PMID- 9512344
TI  - Cross-inhibition of both estrogen receptor alpha and beta pathways by each
      dominant negative mutant.
AB  - Both estrogen receptor alpha (ERalpha) and the recently identified ERbeta are
      nuclear receptors that are activated by estrogen. It was reported that ERalpha
      and ERbeta form heterodimers. Here, we show that they activate transcription
      independently rather than synergistically via estrogen response elements (ERE).
      To show the cross-talk between ERalpha and ERbeta, we utilized dominant negative
      mutants of ERs constructed by C-terminal truncation. Interestingly, ERalpha1-530
      inhibited transactivation not only by ERalpha but also by ERbeta, whereas ERbeta1
      481 inhibited transactivation by ERalpha as well as by ERbeta. The GST pull-down
      assay also demonstrated the cross-interaction of these mutants with wild-type
      ERalpha and ERbeta. Thus, we found dominant negative mutants that block both
      ERalpha and ERbeta signaling pathways.

PMID- 9512345
TI  - Rat messenger RNA for the retinal pigment epithelium-specific protein RPE65
      gradually accumulates in two weeks from late embryonic days.
AB  - The RPE65 protein appears late during the retinal development. To study the basis
      for this regulation, the rat RPE65 cDNA was sequenced and the mRNA subsequently
      quantitated at various stages by competitive RT-PCR. RPE65 mRNA was detected as
      early as E18 (36 copies/ng of whole eye total RNA). It gradually accumulates up
      to P12 (27000 copies/ng) at which point it reaches a steady state level. This
      increase is interrupted for 3 days (P2-P4) during which the levels of mRNA remain
      stable. This timing and rate of accumulation parallels that of rat and mouse
      opsin mRNA and suggests that common factors may control the activation of genes
      in photoreceptors and retinal pigment epithelium cells.

PMID- 9512346
TI  - Selective induction of CD8+ T cell functions by single substituted analogs of an
      antigenic peptide: distinct signals for IL-10 production.
AB  - The CD8+ T cell clone 5F1 produces interleukin 10 (IL-10) and interferon
      gamma(IFN-gamma) in response to stimulation with a peptide corresponding to
      region 142-149 of bovine alpha(s1)-casein (p142-149). Ninety analog peptides
      derived from p142-149 with single amino acid substitutions of putative T cell
      receptor contact residues were prepared to examine whether production of IL-10
      and IFN-gamma by 5F1 can be altered by stimulation with these peptides. We found
      that some peptides triggered only IL-10 production whereas others induced
      production of IFN-gamma alone or both of these cytokines. Peptides inducing IFN
      gamma production triggered both cytotoxicity and a proliferative response,
      whereas peptides inducing production of IL-10 but not IFN-gamma triggered neither
      of these responses. Our results clearly demonstrate that the signaling pathway
      required for IL-10 production in CD8+ T cells differs from that required for IFN
      gamma production. The distinct cellular signals for IL-10 production appear to be
      independent of those for cytotoxicity and the proliferative response of CD8+ T
      cells.

PMID- 9512347
TI  - African origin of GB virus C/hepatitis G virus.
AB  - Ninety-four GB virus C/hepatitis G virus (GBV-C/ HGV) RNA-positive serum samples
      were obtained from all over the world. We found that all 15 GBV-C/HGV isolates
      from the Pygmies and the Bantu in the Central African region had a 12-amino acid
      indel (i.e. insertion or deletion) in the non-structural protein (NS) 5A region.
      Phylogenetic analyses of the NS5A region, using GBV-A as an outgroup, showed that
      these 15 isolates had diverged from the common ancestor much earlier than the
      remaining isolates, indicating an African origin of GBV-C/HGV.

PMID- 9512348
TI  - Son1p is a component of the 26S proteasome of the yeast Saccharomyces cerevisiae.
AB  - A son1 mutant was isolated as a mutant showing synthetic lethality with nin1-1
      which is defective in the p31 component of the regulatory subunit of the yeast
      26S proteasome. son1delta showed a synthetic effect with sen3delta and sun1delta,
      both components of the 26S proteasome, and with cdc28-1N. The 26S proteasome was
      partially purified from the wild type yeast. The FPLC fractions were analyzed by
      Western blotting using anti-Son1p antibody and antibodies against some authentic
      subunits of the 26S proteasome, and we found that Son1p co-migrated with
      components of the 26S proteasome. The 26S proteasome containing fraction was
      immunoprecipitated with anti-Son1p antibody. The resultant precipitate contained
      Nin1p, Sun1p, TBP1, and the 20S proteasome. Combining genetic and biochemical
      results together, we concluded that Son1p is a component of the yeast 26S
      proteasome.

PMID- 9512349
TI  - Regeneration of ultraviolet pigments of vertebrates.
AB  - We report here the regeneration of the visual pigments of mouse, rat, goldfish
      and pigeon, which have wavelengths of maximal absorption at 359 nm, 358 nm, 359
      nm, and 393 nm, respectively. The construction and functional assays of the
      ultraviolet or near-ultraviolet pigments from a wide range of vertebrate species
      will allow us to study the molecular bases of ultraviolet vision for the first
      time.

PMID- 9512350
TI  - Anti-digoxin scFv fragments expressed in bacteria and in insect cells have
      different antigen binding properties.
AB  - A gene encoding a single-chain antibody fragment directed against digoxin (named
      1C10 scFv) was cloned in two expression systems. For this purpose, a new
      baculovirus transfer cassette fully compatible with the procaryotic pHEN vector
      was constructed. Baculovirus production led to higher yield than did Escherichia
      coli expression. The procaryotic fragment showed variations in the fine
      specificity profile but an affinity constant nearly identical to that of the 1C10
      Fab, whereas the eucaryotic scFv fragment had a lower affinity with a specificity
      profile identical to original mAb. The half-lives of the digoxin:scFv complexes
      and the global specificity are compatible with therapeutic use of this antibody
      fragment.

PMID- 9512351
TI  - Effect of pea and bovine trypsin inhibitors on wild-type and modified trypsins.
AB  - In order to modify the catalytic properties of trypsin, lysine-188 (S1) of the
      substrate binding pocket was substituted by an aromatic amino acid residue (Phe,
      Tyr, Trp) or by a histidyl residue. Two other mutants were obtained by
      displacement or elimination of the negative charge of aspartic acid-189
      (K188D/D189K and G187W/K188F/D189Y, respectively). The high affinity inhibitors,
      like PSTI II and BPTI, behaved as specific substrates of the trypsin and its
      mutants. Their inhibiting effect toward modified trypsins was studied. The bovine
      inhibitor had a higher affinity for all tested enzymes than pea inhibitor. The
      inhibition constants differed according to the mutations on the protease.

PMID- 9512352
TI  - Alpha1-syntrophin has distinct binding sites for actin and calmodulin.
AB  - Overlay and co-sedimentation assays using recombinant alpha1-syntrophin proteins
      revealed that two regions of alpha1-syntrophin, i.e. aa 274-315 and 449-505,
      contain high-affinity binding sites for F-actin (Kd 0.16-0.45 microM), although
      only a single high-affinity site (Kd 0.35 microM) was detected in the recombinant
      full-length syntrophin. We also found that actomyosin fractions prepared from
      both cardiac and skeletal muscle contain proteins recognized by anti-syntrophin
      antibody. These data suggest a novel role for syntrophin as an actin binding
      protein, which may be important for the function of the dystrophin-glycoprotein
      complex or for other cell functions. We also found that alpha1-syntrophin binds
      calmodulin at two distinct sites with high (Kd 15 nM) and low (Kd 0.3 microM)
      affinity.

PMID- 9512353
TI  - Thylakoid protein phosphorylation in evolutionally divergent species with
      oxygenic photosynthesis.
AB  - Phosphothreonine antibody was used to explore reversible thylakoid protein
      phosphorylation in vivo in evolutionally divergent organisms with oxygenic
      photosynthesis. Three distinct groups of organisms were found. Cyanobacteria and
      red algae, both with phycobilisome antenna system, did not show phosphorylation
      of any of the photosystem II (PSII) proteins and belong to group 1. Group 2
      species, consisting of a moss, a liverwort and a fern, phosphorylated both the
      light-harvesting chlorophyll alb proteins (LHCII) and the PSII core proteins D2
      and CP43, but not the D1 protein. Reversible phosphorylation of the D1 protein
      seems to be the latest event in the evolution of PSII protein phosphorylation and
      was found only in seed plants, in group 3 species. Light-intensity-dependent
      regulation of LHCII protein phosphorylation was similar in group 2 and 3 species,
      with maximal phosphorylation of LHCII at low light and nearly complete
      dephosphorylation at high light.

PMID- 9512354
TI  - An Arabidopsis cDNA encodes an apparent polyprotein of two non-identical
      thylakoid membrane proteins that are associated with photosystem II and
      homologous to algal ycf32 open reading frames.
AB  - We have characterised an Arabidopsis thaliana cDNA homologous to the ycf32 open
      reading frames present in the Synechocystis genome and the plastid genomes of
      several eukaryotic algae. The predicted protein is also homologous to a novel
      protein reported to be associated with photosystem II. The protein is synthesised
      as a 23 kDa precursor with an N-terminal presequence that appears to be bipartite
      in structure, and the protein is targeted into the thylakoid membrane of pea
      chloroplasts. Although the Ycf32 presequence contains an apparent signal peptide,
      we find that this protein is not imported by either of the standard Sec- or
      deltapH-dependent pathways. The mature protein is also unusual in two respects.
      First, there are two distinct, non-identical copies of typical single-span Ycf32
      sequences in the Arabidopsis sequence, separated by an additional hydrophobic
      region. Secondly, the imported protein runs as a doublet of 6 kDa and 7 kDa
      polypeptides whereas the mature protein is predicted to be 14 kDa. We speculate
      that the protein undergoes further maturation once inserted into the thylakoid
      membrane to yield two separate Ycf32-like polypeptides.

PMID- 9512355
TI  - Mutant T7 RNA polymerase is capable of catalyzing DNA primer extension reaction.
AB  - The mutant T7 RNA polymerase (T7 RNAP), containing two substitutions (Y639F,
      S641A) was earlier shown to utilize both rNTP and dNTP in a transcription-like
      reaction. In this report the ability of the enzyme to catalyze DNA primer
      extension reaction was demonstrated. The efficiency of the reaction essentially
      depended on the type of the primer sequence, and was significantly higher if the
      primer coincided with the T7 promoter non-coding sequence. In this case the
      primer extension reaction proceeded along with de novo RNA synthesis. The length
      of the product did not exceed 8 nucleotides, indicating that the primer extension
      reaction proceeds according to the mechanism of the T7 RNAP-catalyzed abortive
      transcription.

PMID- 9512356
TI  - Alu elements in a Plasmodium vivax antigen gene.
AB  - Plasmodium vivax is a very common human malaria parasite but it is poorly
      characterized at the molecular level. Here, we describe the isolation and
      characterization of an antigen coding gene of P. vivax which contains Alu
      elements. This gene, called Pv-Alu, is expressed during the erythrocytic phase of
      the parasite. The encoded 200 amino acid long polypeptide is highly hydrophobic,
      contains transmembrane domains, and is rich in leucine (19.4%), serine (15.9%),
      proline (15.4%) and phenylalanine (15.4%). The 5'-untranslated region and part of
      the 3'-end coding region of Pv-Alu show significant homology to different Alu
      families. The presence of Alu elements in the coding region of a parasite antigen
      gene is significant from a functional and evolutionary viewpoint.

PMID- 9512358
TI  - Structural dynamics of the Streptomyces lividans K+ channel (SKC1): secondary
      structure characterization from FTIR spectroscopy.
AB  - Fourier transform infrared (FTIR) spectroscopy was used to probe the secondary
      structure, orientation, and the kinetics of amide hydrogen-deuterium exchange
      (HX) of the small K+ channel from Streptomyces lividans. Frequency component
      analysis of the amide I band showed that SKC1 is composed of 44-46% alpha-helix,
      21-24% beta-sheet, 10-12% turns and 18-20% unordered structures. The order
      parameter S of the helical component of SKC1 was between 0.60 and 0.69. Close to
      80% of SKC1 amide protons exchange within approximately 3 h of D2O exposure,
      suggesting that the channel is largely accessible to solvent exchange. These
      results are consistent with a model of SKC1 in which helices slightly tilted from
      the membrane normal line the water-filled vestibules that flank the K+
      selectivity filter.

PMID- 9512357
TI  - Calcium currents and transients of native and heterologously expressed mutant
      skeletal muscle DHP receptor alpha1 subunits (R528H)
AB  - Rabbit cDNA of the alpha1 subunit of the skeletal muscle dihydropyridine (DHP)
      receptor was functionally expressed in a muscular dysgenesis mouse (mdg) cell
      line, GLT. L-type calcium currents and transients were recorded for the wild type
      and a mutant alpha1 subunit carrying an R528H substitution in the supposed
      voltage sensor of the second channel domain that is linked to a human disease,
      hypokalemic periodic paralysis. L-type channels expressed in GLT myotubes
      exhibited currents similar to those described for primary cultured mdg cells
      injected with rabbit wild type cDNA, indicating this system to be useful for
      functional studies of heterologous DHP receptors. Voltage dependence and kinetics
      of activation and inactivation of L-type calcium currents from mutant and wild
      type channels did not differ significantly. Intracellular calcium release
      activation measured by fura-2 microfluorimetry was not grossly altered by the
      mutation either. Analogous measurements on myotubes of three human R528H carriers
      revealed calcium transients comparable to controls while the voltage dependence
      of both activation and inactivation of the L-type current showed a shift to more
      negative potentials of approximately 6 mV. Similar effects on the voltage
      dependence of the fast T-type current and changes in the expression level of the
      third-type calcium current point to factors not primarily associated with the
      mutation perhaps participating in disease pathogenesis.

PMID- 9512359
TI  - Long lasting facilitation of the rabbit cardiac Ca2+ channel: correlation with
      the coupling efficiency between charge movement and pore opening.
AB  - Facilitation of Ca2+ entry into cells enhances Ca(2+)-activated events such as
      transmitter release and stimulation of second messenger systems. We have found a
      long lasting prepulse facilitation (up to 3-fold) of the cardiac Ca2+ channel
      alpha1Cbeta1b that lasts for tens of seconds without altering current kinetics.
      The voltage- and time-dependence of the installation of facilitation was
      characterized as well as the time- and use-dependence of the decay of
      facilitation. The degree of facilitation was correlated with the coupling
      efficiency between the charge movement and pore opening channels that were poorly
      coupled prior to facilitation exhibited the largest facilitation.

PMID- 9512360
TI  - Colon carbonic anhydrase 1: transactivation of gene expression by the homeodomain
      protein Cdx2.
AB  - The homeodomain protein, Cdx2, has been implicated in the transcriptional
      regulation of genes expressed in the small intestine. In vitro studies of the
      carbonic anhydrase 1 (CA1) colon promoter implied that Cdx2 may also play a role
      in the regulation of colon-specific gene expression. The current work follows up
      this proposal by examining the ability of Cdx2 to transactivate gene expression
      in cultured cells mediated by CA1 promoter sequences. The results show that Cdx2
      exerts a positive regulatory effect by binding to a motif 87 bp upstream of the
      CA1 TATA box; this motif appears to act as an enhancer since gene activation is
      independent of its orientation.

PMID- 9512361
TI  - Identification of tryptophan 55 as the primary site of [3H]nicotine
      photoincorporation in the gamma-subunit of the Torpedo nicotinic acetylcholine
      receptor.
AB  - [3H]nicotine has been used as a photoaffinity agonist to identify amino acids
      within the Torpedo nicotinic acetylcholine receptor (nAChR) gamma-subunit that
      contributes to the structure of the agonist binding site. UV irradiation (254 nm)
      of nAChR-rich membranes equilibrated with [3H]nicotine results in covalent
      incorporation into alpha- and gamma-subunits that is inhibitable by agonists and
      competitive antagonists, but not by non-competitive antagonists (Middleton, R.E.
      and Cohen, J.B. (1991) Biochemistry 30, 6887-6897). To identify sites of specific
      incorporation, SDS-PAGE and reversed-phase HPLC were used to isolate proteolytic
      fragments of [3H]nicotine-labeled gamma-subunit. Amino-terminal sequence analysis
      identified gammaTrp-55 as the major site of [3H]nicotine photoincorporation in
      gamma-subunit. Thus gammaTrp-55 is the first amino acid within a non-alpha
      subunit to be identified by affinity labeling in direct contact with a bound
      agonist.

PMID- 9512362
TI  - Effect of heparin on phosphorylation site specificity of neuronal Cdc2-like
      kinase.
AB  - Neuronal Cdc2-like kinase (Nclk) can be stimulated by heparin in a substrate
      dependent manner. While phosphorylation of tau is markedly enhanced by heparin,
      phosphorylation of histone H1 by Nclk is essentially unaffected. A histone H1
      peptide, HS(9-18): PKTPKKAKKL, and its substitution analogues were used to
      examine the basis of the differential heparin effect. In the presence of heparin,
      the phosphorylation site specificity of Nclk is altered and only proline
      immediately following the phosphorylation site is still an essential substrate
      determinant. This change in the site specificity may adequately account for the
      differential heparin effect on histone H1 and tau phosphorylation.

PMID- 9512363
TI  - Sulphite enhances peroxynitrite-dependent alpha1-antiproteinase inactivation. A
      mechanism of lung injury by sulphur dioxide?
AB  - Sulphite is toxic to the lung and can cause allergic reactions, the most common
      of which is bronchoconstriction in asthmatics. We show that sulphite can
      considerably potentiate the inactivation of alpha1-antiproteinase caused by
      peroxynitrite. Addition of peroxynitrite to sulphite generated inactivating
      species that persisted at pH 7.4 and 37 degrees C for at least 30 min. We propose
      that formation of protein-modifying sulphite radicals from SO3(2-) exposed to
      ONOO- is a mechanism by which SO2 could cause lung injury, both by enhancing
      proteolysis and by creating new antigens that could provoke an immune response.

PMID- 9512364
TI  - Transactivation potential of the C-terminus of human Nm23-H1.
AB  - The transactivation potential of Nm23-H1, a homolog of c-myc transcription factor
      Nm23-H2/PuF was assessed in yeast as a fusion protein with the DNA binding
      domains (DBDs) of GAL4 and LexA. The C-terminal half of Nm23-H1 exhibited strong
      transactivation of the reporter genes, LacZ and Leu2 carrying GAL4 and LexA
      upstream activating sequences (UASs), whereas the full-length Nm23-H1 and its N
      terminal did not. Similar results were also obtained with Nm23-H2/PuF
      transactivating the reporter genes only by the C-terminus fused to GAL4 and LexA
      DBDs. Hence, our results suggested a possible regulatory role of the N-termini of
      Nm23 isotypes upon transactivation.

PMID- 9512365
TI  - A new family of cytokinin receptors from Cereales.
AB  - The highly specific recognition of a natural cytokinin, trans-zeatin, by
      cytokinin-binding protein (CBP) of 67 kDa from barley leaves was detected with an
      assay developed on the basis of cytokinin competition in ELISA with anti-idiotype
      antibodies (raised against antibodies to zeatin) for complex formation with CBP.
      Monoclonal antibodies (mAbs) raised against 70 kDa CBP from etiolated maize
      seedlings cross-reacted with barley 67 kDa CBP and prevented barley CBP and trans
      zeatin induced activation of transcription elongation directed by RNA polymerase
      I associated with barley chromatin. One mAb (Z-6) had an agonistic effect. Maize
      CBP replaced barley CBP in activation of RNA synthesis with cytokinin in the
      barley transcription system. Hence, a new family of cytokinin receptors with
      common functions and immunodeterminants including maize and barley CBPs was
      found.

PMID- 9512366
TI  - Involvement of ecto-ATPase and extracellular ATP in polymorphonuclear granulocyte
      endothelial interactions.
AB  - The adhesion of human polymorphonuclear granulocytes (PMN) with confluent human
      endothelial cells (line EAhy926) and with solid substrate coated by collagen and
      fibronectin (Fn) was studied by phase contrast microscopy and by the measurement
      of myeloperoxidase activity. The ecto-ATPase inhibitors suramin and Reactive Blue
      2 (RB2) more than doubled the adhesion of PMN to endothelial cells. The cells
      hydrolyzed added ATP and this reaction was inhibited by suramin and RB2. The
      degree of ATP hydrolysis during PMN adherence depended on solid substrata and
      decreased in the order: non-stimulated endothelial cells, TNF-stimulated
      endothelial cells, collagen-coated surface, Fn-coated surface. In the same order
      adherence increased. The endogenous level of extracellular ATP in the PMN
      endothelial coculture was around 25 nM. We conclude that PMN-endothelial adhesion
      is counteracted by an ecto-ATPase or by ATP receptors with ATPase activity. Such
      interactions may play a role in PMN rolling and diapedesis as well as in the
      pathophysiology of PMN activation by an anergic endothelium.

PMID- 9512367
TI  - Identification of neutral and acidic sphingomyelinases in Helicobacter pylori.
AB  - We demonstrated for the first time the presence of sphingomyelinase (SMase) in
      Helicobacter pylori. Activation of SMase has been implicated as the cause of
      elevation of cellular ceramide levels and consequently of apoptosis. The data
      indicate that there are two classes of SMase, defined by their optimal pHs and
      cellular locations, existing in H. pylori. One is an Mg(2+)-dependent membrane
      bound enzyme with an optimal activity at pH 7, and the other is an Mg(2+)
      independent cytosolic enzyme with an optimal activity at pH 5. Bisalumin, a
      bismuth salt, was found to inhibit the activities of both forms of SMase
      regardless of the presence of Mg2+. By Western blot analysis, the membrane-bound
      SMases of H. pylori and Bacillus cereus were shown to be antigenically related
      and to have a similar denatured molecular mass of 28 kDa.

PMID- 9512368
TI  - Evidence against structural and functional identity of microtubule-associated
      protein 1B and proteoglycan claustrin.
AB  - Recently, the concept of microtubule-associated protein 1B as an intracellular
      2460 amino acid protein was challenged by the suggestion that only the N-terminal
      1022 codons are utilized and encode the core protein of the extracellular
      proteoglycan claustrin (Burg and Cole (1994) J. Neurobiol. 25, 1-22). We
      expressed this N-terminal MAP1B fragment in tissue culture cells and found that
      it bound to microtubules and was not localized in the extracellular matrix. In
      addition, epitope mapping demonstrated that MAP1B consisted of more than 1022
      amino acids and that the reported cDNA of claustrin is incomplete.

PMID- 9512369
TI  - Expression of two isoforms of the third sarco/endoplasmic reticulum Ca2+ ATPase
      (SERCA3) in platelets. Possible recognition of the SERCA3b isoform by the
      PL/IM430 monoclonal antibody.
AB  - Human platelets express several sarco/endoplasmic reticulum Ca2+ ATPase (SERCA)
      isoenzymes: SERCA2b of 100 kDa apparent molecular mass and two distinct enzymes
      of 97 kDa, one of them identified as being the SERCA3a isoform. The molecular
      identity of the third enzyme specifically recognized by the PL/IM430 monoclonal
      antibody has remained elusive. First, the study of the 3'-end part of platelet
      SERCA3 mRNA, by means of RT-PCR amplification using sets of primers covering the
      N-3 to N (ultimate) exons of the human SERCA3 sequence, revealed the presence of
      two distinct mRNA sequences, SERCA3a and a longer variant. Second, this
      additional sequence was identified as SERCA3b and found to refer to the insertion
      of a new exon of 73 bp, located at bp 349 from the beginning of the intronic
      sequence, linking the penultimate (N-1) exon to the last exon (N) of the human
      SERCA3 gene. Third, a relationship between the expression of this SERCA3b mRNA
      and the PL/ IM430 recognizable SERCA protein was observed. SERCA3b mRNA was found
      to be absent in epithelial HeLa cells not recognized by the PL/IM430 antibody and
      the expression of this SERCA3b RNA species correlated with that of the SERCA
      protein recognized by PL/IM430 which was down-modulated in the platelet precursor
      megakaryocytic CHRF 288-11 cell line as well as upon in vitro lymphocyte
      activation. Taken together, these results strongly support the notion of the
      presence of the SERCA3b protein in human cells by showing SERCA3b mRNA in
      platelets and the fact that the protein corresponding to this mRNA species is
      very likely the 97 kDa protein recognized by the PL/IM430 antibody.

PMID- 9512370
TI  - Acid induced equilibrium unfolding of annexin V wild type shows two intermediate
      states.
AB  - Annexin V is an alpha-helical protein which shows anticoagulatory and
      antiinflammatory activity. It is supposed to be involved in membrane fusion and
      exocytosis. In this study acid-induced equilibrium unfolding of the human annexin
      V is investigated by fluorescence and circular dichroism spectroscopy. The
      spectroscopic data indicate that at least two intermediate states are involved in
      unfolding. One of the proposed intermediate states exhibits properties similar to
      those observed with annexin V wild type saturated with calcium, another may be
      regarded as 'molten globule'.

PMID- 9512371
TI  - The neuropsychology of REM sleep dreaming.
AB  - Recent PET imaging and brain lesion studies in humans are integrated with new
      basic research findings at the cellular level in animals to explain how the
      formal cognitive features of dreaming may be the combined product of a shift in
      neuromodulatory balance of the brain and a related redistribution of regional
      blood flow. The human PET data indicate a preferential activation in REM of the
      pontine brain stem and of limbic and paralimbic cortical structures involved in
      mediating emotion and a corresponding deactivation of dorsolateral prefrontal
      cortical structures involved in the executive and mnemonic aspects of cognition.
      The pontine brainstem mechanisms controlling the neuromodulatory balance of the
      brain in rats and cats include noradrenergic and serotonergic influences which
      enhance waking and impede REM via anticholinergic mechanisms and cholinergic
      mechanisms which are essential to REM sleep and only come into full play when the
      serotonergic and noradrenergic systems are inhibited. In REM, the brain thus
      becomes activated but processes its internally generated data in a manner quite
      different from that of waking.

PMID- 9512372
TI  - Leukemia inhibitory factor maintains choline acetyltransferase expression in
      vivo.
AB  - Following axotomy most medial septal neurons in the adult rat brain have
      dramatically reduced numbers of choline acetyltransferase (ChAT) positive
      neurons. Since leukemia inhibitory factor (LIF) promotes cholinergic expression
      in several neuronal populations, the aim of this study was to determine if LIF
      would continue to support cholinergic expression in axotomized medial septal
      neurons. Mini-osmotic pumps were used to infuse saline or LIF into the lateral
      cerebral ventricle. Counts of ChAT and low-affinity nerve growth factor (p75NGFR)
      immunostained neurons indicated that LIF-treated animals retained ChAT expression
      in > 90% of axotomized neurons whereas in saline-infused animals this was < 30%.
      Also, LIF was equally effective in maintaining p75NGFR expression levels in
      axotomized medial septal neurons.

PMID- 9512373
TI  - Nitric oxide mediates behavioral signs of neuropathic pain in an experimental rat
      model.
AB  - This study was conducted to determine whether nitric oxide (NO) is involved in
      the maintenance of behavioral signs of neuropathic pain induced by tightly
      ligating the left L5 and L6 spinal nerves. Neuropathic rats showed behavioral
      signs representing mechanical allodynia, cold allodynia and cold-stress
      exacerbated ongoing pain. Mechanical allodynia was suppressed by Nomega-nitro-L
      arginine methyl ester (L-NAME; 200, 100, 50, 10 microM/kg, i.p.), a nitric oxide
      synthase inhibitor, in a dose-dependent manner. Cold allodynia and cold-stress
      exacerbated ongoing pain was also attenuated by L-NAME. Neither Nomega-nitro-D
      arginine methyl ester (D-NAME; 200 microM/kg) nor saline changed any of the
      neuropathic pain behaviors. These results suggested that NO plays an important
      role in the maintenance of the behavioral signs of neuropathic pain and is
      involved in common steps in the maintenance of the different modalities of pain
      such as mechanical allodynia and cold allodynia.

PMID- 9512374
TI  - c-Fos induction in the rostroventrolateral medulla by 5-HT3 receptor activation
      in the nucleus tractus solitarius.
AB  - The nucleus tractus solitarius (NTS) plays a crucial role in the reflex control
      of sympathetic tone through direct projections to the caudal and rostral regions
      of the ventrolateral medulla (CVLM and RVLM respectively). 5-HT3 receptor
      stimulation in the NTS increases both blood pressure and sympathetic tone. In
      order to investigate whether the ventrolateral medulla participates in these
      effects, the expression of c-Fos protein, a marker of neuronal activation, was
      examined at this level after intra-NTS microinjections of 1-(m-chlorophenyl)
      biguanide, a selective 5-HT3 receptor agonist. A marked increase (93%) in the
      density of c-Fos-immunoreactive neurons was restricted to the most rostral part
      of the RVLM after this treatment. This effect could be prevented by prior intra
      NTS microinjection of ondansetron, a selective 5-HT3 antagonist. These results
      suggest the participation of sympathoexcitatory neurons in the rostral RVLM in
      the pressor response to 5-HT3 receptor stimulation in the NTS.

PMID- 9512375
TI  - Neurosteroids act on the GABA(A) receptor at sites on the N-terminal side of the
      middle of TM2.
AB  - Two sets of chimeras between alphaxalone-sensitive GABA(A) receptor alpha2 or
      beta1 subunits and the alphaxalone-insensitive glycine receptor alpha1 subunit
      were constructed to determine the structural domains important for the modulatory
      actions of neuroactive steroids. These data suggest that the site of action for
      neurosteroids on GABA(A) receptors is not the same as that for volatile
      anesthetics and ethanol, but is on the N-terminal side of the middle of TM2.

PMID- 9512376
TI  - Immunoreactivity for endomorphin-2 occurs in primary afferents in rats and
      monkey.
AB  - Antisera were raised against endomorphin-2, a recently isolated endogenous opioid
      peptide that binds potently and selectively to the mu-opioid receptor. When
      sections of spinal cord were stained immunocytochemically, a dense plexus of
      fibres and varicosities was visualized in the superficial dorsal horn of rats and
      one monkey. Following unilateral multiple dorsal rhizotomy, labeling for
      endomorphin-2 was markedly reduced ipsilateral to the lesion. In sections stained
      for both endomorphin-2 and CGRP, double-labeling was observed. Taken together,
      these data suggest that endomorphin-2 occurs in small diameter primary afferent
      fibres in rodents and primates. It appears possible that the release of
      neurotransmitters from nociceptive primary afferents might be regulated by
      release of endomorphin-2 from primary afferent terminals.

PMID- 9512377
TI  - Changes in mRNA abundance of microtubule-associated proteins in the rat brain
      following electroconvulsive shock.
AB  - Microtubule-associated proteins (MAPs) are involved in the maintenance of mature
      neuronal morphology, neurite outgrowth and neuronal plasticity. Alteration in MAP
      expression may underlie neuronal structural changes in response to seizure
      activity. The aim of the present study was to investigate whether
      electroconvulsive shock (ECS), an animal model of electroconvulsive therapy (ECT)
      in clinical treatment of depression, affected gene expression of MAPs in the rat
      brain. Using in situ hybridization, we studied the expression of encoding mRNA
      for MAPs in the brains of rats treated with ECS 5 times over 10 days. The
      abundance of mRNA encoding microtubule-associated protein 2 (MAP2), a dendritic
      MAP, was significantly increased (142% compared with controls) in the dentate
      gyrus 6 and 24 h after the last shock, and had returned to baseline levels within
      48 h. These changes were confined to the dentate gyrus no significant changes
      were observed in CA1 and CA3 of the hippocampus. The increase in MAP2 expression
      was accompanied by an increase in MAP2 immunoreactivity in the molecular layer of
      the dentate gyrus. The abundance of mRNA encoding for tau, an axon-specific MAP,
      and MAP1B, an embryonic MAP, was unaffected by ECS. These data demonstrate that
      ECS specifically altered the mRNA and protein expression of MAP2 but had no
      effect on tau or MAP1B, and suggest that changes in MAP2 expression may be
      related to morphological changes in the dentate gyrus, particularly in the
      dendrites.

PMID- 9512378
TI  - The role of anticipatory postural adjustments during whole body forward reaching
      movements.
AB  - The purpose of this study was to examine the role of anticipatory postural
      adjustments (APAs) in the execution of forward oriented whole body reaching
      movements. From the standing position, eight healthy subjects were asked to reach
      an object placed at 45 cm from the feet, at both naturally paced and fast speeds.
      Electromyographic signals of six antagonistic muscles were analysed in
      conjunction with centre of mass (CM) displacements, centre of foot pressure
      displacements and resultant ground reaction forces. Results revealed that APAs
      created necessary angular momentum of body segments for effective task execution.
      These results suggest that APAs can initiate movements conducted from a fixed
      base of support, and in this context do not act solely to stabilize the CM.

PMID- 9512379
TI  - Metabotropic glutamate receptors are necessary for sensitization by amphetamine.
AB  - The contribution of metabotropic glutamate receptors (mGluRs) in the ventral
      tegmental area (VTA) to the induction of locomotor sensitization by amphetamine
      (AMPH) was investigated. Rats pre-exposed to AMPH in the VTA showed significantly
      higher locomotor activity when subsequently tested with a systemic AMPH challenge
      than rats preexposed to VTA saline. Rats pre-exposed to AMPH but co-injected with
      the selective mGluR antagonist (RS)-alpha-methyl-4-carboxyphenylglycine [(RS)
      MCPG] did not show this effect. These findings indicate that activation of mGluRs
      in the VTA is necessary for the induction of locomotor sensitization by AMPH and
      provide further support for the important role played by excitatory amino acids
      in this site in the development of sensitization to AMPH.

PMID- 9512380
TI  - Cerebral hemodynamics during electrically induced seizures.
AB  - Electroconvulsive therapy (ECT) is an appropriate clinical model to investigate
      blood flow during seizures. In this study cerebral blood flow velocity (CBFV) was
      measured during 40 ECTs in 10 patients by means of transcranial Doppler
      sonography. EEG was recorded continuously. Under general anesthesia, the pre
      convulsive blood flow velocity (Vmean) decreased significantly. After ECT, we
      measured a dramatic increase in Vmean which was significantly greater in the left
      MCA than in the right MCA. After termination of seizures, flow velocities
      returned to baseline levels. The striking increase in cerebral blood flow
      velocity reflects excessive cerebral metabolism during convulsive neuronal
      activation. The left hemisphere seems to be more sensitive to electrical stimuli
      as was indicated by its predominant augmentation of CBFVs.

PMID- 9512381
TI  - Pontine projections of pulmonary slowly adapting receptor relay neurons in the
      cat.
AB  - Pontine projections of second-order neurons activated by vagal afferents
      originating from pulmonary slowly adapting receptors were studied
      electrophysiologically in Nembutal-anesthetized, paralyzed and artificially
      ventilated cats. Extracellular recordings from these neurons (referred to as P
      cells) were made in the nucleus tractus solitarii. Antidromic mapping of the
      brain stem showed that many P-cells examined projected their axons to the
      ipsilateral pons as well as the medulla. Axonal arborizations were found in the
      parabrachial nucleus, i.e. in the area corresponding to the pontine respiratory
      group. In some P-cells, axonal arborizations were also found in the A5 area. The
      present results suggest that the P-cells are involved in pontine pneumotaxic
      mechanisms.

PMID- 9512382
TI  - Nitric oxide of neuronal origin mediates NMDA-induced cerebral hyperemia in rats.
AB  - The goal of this study was to determine whether neuronally derived nitric oxide
      mediates responses of cerebral blood flow (CBF) to N-methyl-D-aspartate (NMDA).
      In anesthetized Sprague-Dawley rats, regional CBF of the parietal cortex was
      monitored by laser-Doppler flowmetry. Topical application of either NMDA or
      acetylcholine produced concentration-related increases in CBF. Responses of CBF
      to NMDA (10(-5) M) but not to acetylcholine were inhibited (0+/-3% vs 21+/-5%, p
      < 0.05) by 7-nitroindazole (50 mg/kg, i.p.). MK-801 (0.5 mg/kg, i.v.) and
      tetrodotoxin (10(-6) M, topical application) also inhibited NMDA-induced
      responses. These results suggest that nitric oxide of neuronal origin mediates
      NMDA-induced increases in CBF.

PMID- 9512383
TI  - Stages of estrous mediate the stress-induced impairment of associative learning
      in the female rat.
AB  - Exposure to a stressful event facilitates classical eyeblink conditioning in male
      rats and impairs conditioning in females. The contribution of stages of estrous
      to the stress-induced impairment of eyeblink conditioning was evaluated. Females
      in proestrus, estrus and diestrus were either exposed to an acute stressor of
      intermittent tailshocks or swim stress and compared to unstressed females in the
      three stages. Females in proestrus, when estrogen levels are high, acquired the
      conditioned response at a facilitated rate relative to females in other stages.
      However, exposure to a stressor of either intermittent tailshocks or inescapable
      swim stress severely impaired acquisition in females during proestrus. These
      results suggest that the enhancing effect of estrogen on procedural memory
      formation is disrupted by previous exposure to a stressful event.

PMID- 9512384
TI  - MRI white matter diffusion anisotropy and PET metabolic rate in schizophrenia.
AB  - A disturbance in the frontal-striatal-thalamic circuitry has been proposed for
      schizophrenia, but this concept has been based primarily on indirect evidence
      from psychopharmacology and analogies with animal research. Diffusion tensor
      imaging, a new MRI technique that permits direct assessment of the large axon
      masses stretching from the prefrontal cortex to the striatum, was used to study
      white matter axon bundles. Diffusion tensor images, high-resolution structural
      MRI and positron emission tomography scans with 18-fluorodexoyglucose were
      obtained on five patients with schizophrenia and six age- and sex-matched normal
      controls. Significantly lower diffusion anisotropy in the white matter of the
      prefrontal cortex in schizophrenic patients than in normal controls was observed
      in statistical probability maps. Co-registered PET scans revealed significantly
      lower correlation coefficients between metabolic rates in the prefrontal cortex
      and striatum in patients than in controls. These twin findings provide convergent
      evidence for diminished fronto-striatal connectivity in schizophrenia.

PMID- 9512385
TI  - Amikacin intoxication induces apoptosis and cell proliferation in rat organ of
      Corti.
AB  - Recently, an attempt at cochlear hair cell neodifferentiation has been reported
      in amikacin-treated rats. In the present study, we aimed to ascertain whether
      hair cell losses are mediated by apoptosis and whether cell proliferation occurs
      in damaged intoxicated cochleas. The results show that apoptosis is responsible
      for hair cell losses and that cell proliferation occurs in the region of the
      outer spiral sulcus but not in the region of Deiters cells and pre-existing hair
      cells. We suggest that cell proliferation maintains a certain homeostasis in the
      number of non-sensory cells and participates in epithelial scar formation.
      Neodifferentiated cells therefore probably arise from direct
      transdifferentiation, which could be triggered by phagocytosis of apoptotic
      bodies.

PMID- 9512386
TI  - Synaptic depression at type B to A photoreceptor connections in Hermissenda.
AB  - We quantified synaptic depression at the type B to A photoreceptor connections of
      Hermissenda. Type B cell action potentials were evoked at interstimulus intervals
      (ISIs) of 0.3, 3 or 30 s and the resulting inhibitory postsynaptic potentials
      (IPSPs) were recorded in a type A cell. A progressive decline in IPSP amplitude
      occurred at all three ISIs. Synaptic depression was greater at shorter ISIs, as
      was the level of recovery 2 min after the stimulus series. The profound level of
      synaptic depression observed (79.0+/-3.2% at the 0.3 s ISI) implies that synaptic
      depression is an important control process in the neuronal circuitry that drives
      phototactic behavior.

PMID- 9512387
TI  - Effect of glutamate transporter on neuronal damage induced by photochemical
      thrombotic brain ischemia.
AB  - To study the effects of glutamate transporters on the pathogenesis of brain
      infarct, pharmacological and histological analyses were carried out on the
      thrombotic focal ischemic model. Expression of mRNA coding for the glutamate
      transporter GLAST increased significantly in the penumbra at 72 h following the
      ischemia. Combined with confocal laser scanning microscopic analysis, double
      staining showed expression of GLAST mRNA in both neurons and glial cells in the
      penumbra. L-trans-Pyrrolidine-2,4-dicarboxylate (L-trans-PDC), a glutamate uptake
      inhibitor, dose-dependently enhanced the volume of the infarct induced by the
      ischemia. The results suggest that a compensatory increase in the activity of
      glutamate transporter may accompany pathological changes after ischemic injury.

PMID- 9512388
TI  - Effects of K+ channel blockers on the anoxic response of CNS myelinated axons.
AB  - Compound action potentials (CAPs) from adult rat optic nerves were recorded in
      vitro. The area under the CAP was compared before and after 1 h
      anoxia/reoxygenation. Resting compound membrane potential was measured using the
      cold grease-gap technique. The acute reduction of CAP magnitude by anoxia was
      unaffected by TEA (20 mM), 4-AP (300 microM), or the KATP blockers glibenclamide
      (300 microM) and tolbutamide (2 mM). Neither these K+ channel blockers, nor
      glipizide (100 microM) or the KATP activator diazoxide (500 microM) altered post
      anoxic CAP area recovery. In contrast, although Cs+ (5 mM) accelerated anoxic CAP
      failure and membrane depolarization, this cation significantly increased CAP area
      recovery post-anoxia from 22+/-10% (s.d.) to 60+/-22% (p < 0.0001). The unique
      effects of Cs+ suggest that inward rectifier channels may play an important role
      in the induction of anoxic injury in optic nerve axons.

PMID- 9512389
TI  - The magnetic mismatch field elicited by words and phonological non-words.
AB  - The speech-evoked magnetic mismatch field was measured using a 49-channel
      gradiometer. The standard stimuli were words in one condition and phonological
      non-words in another condition. The deviants were non-words throughout. The
      equivalent current dipole fitted to the mismatch field was deeper inside the
      brain and its dipole moment was stronger for non-word than word standards. The
      factor structure of field amplitude, source dipole moment, and depth suggested
      that the lexicality conditions differed in source surface area and depth, but not
      in source current density. This lexicality effect is compatible with a modular
      rather than an interactive view of the relationship between lexical and phonetic
      representation.

PMID- 9512390
TI  - NCAM-180 knockout mice display increased lateral ventricle size and reduced
      prepulse inhibition of startle.
AB  - NCAM-180 knockout mice, which have documented deficits in neural migration, were
      used to determine whether developmental abnormalities could lead to morphological
      changes and alterations in sensory motor gating mechanisms. Measurement of the
      lateral ventricle showed that NCAM-180-/- mice had marked increases in both the
      left and right anterior horns of the lateral ventricle. Furthermore, these mice
      also displayed a reduction of prepulse inhibition that was differentially
      affected by the dopamine agonist apomorphine. These results are discussed in
      light of the known increase in lateral ventricle size and reduction in prepulse
      inhibition that are seen in schizophrenia.

PMID- 9512391
TI  - Chandelier cell axons are immunoreactive for GAT-1 in the human neocortex.
AB  - We have examined the pattern of immunostaining for the high-affinity GABA
      transporter GAT-1 in the human temporal neocortex. Immunocytochemistry for GAT-1
      labels terminal-like puncta in the neuropil and around unstained cell bodies. The
      characteristic terminal portions of chandelier cell axons (Ch-terminals, which
      form multiple inhibitory GABAergic synaptic contacts with the axon initial
      segments of pyramidal cells) were among the strongest immunocytochemically
      stained elements for GAT-1. Since Ch-terminals are immunoreactive for the calcium
      binding protein parvalbumin, experiments were carried out to study the co
      localization of GAT-1 and parvalbumin in Ch-terminals. These experiments showed
      that the vast majority of Ch-terminals immunoreactive for GAT-1 were also
      immunoreactive for PV. We concluded that GAT-1 transporter may have an important
      functional role in controlling pyramidal cell activity.

PMID- 9512392
TI  - Attenuation of focal cerebral infarct in mice lacking NMDA receptor subunit NR2C.
AB  - Neuronal death following cerebral vascular occlusion may be caused in part by the
      action of glutamate acting through the NMDA receptor. Here we demonstrate that
      gene disruption of the NR2C subunit of the NMDA receptor attenuates focal
      cerebral ischemic injury after permanent MCA occlusion, and that a low level of
      NR2C is expressed and active in the cerebral cortex. NR2C-deficient mice do not
      show impairment of motor coordination or motor learning. Therefore the
      development of drugs selectively inhibiting NR2C may prove beneficial in the
      treatment of stroke and traumatic brain injuries.

PMID- 9512393
TI  - No evidence for disruption of normal patterns of mRNA localization in dendrites
      or dendritic transport of recently synthesized mRNA in FMR1 knockout mice, a
      model for human fragile-X mental retardation syndrome.
AB  - Recent studies have revealed that FMRP, the gene product of the fragile-X gene
      FMR1, is an RNA-binding protein. These and other data have led to the idea that
      FMRP may play a role in targeting mRNAs for transport to synaptic sites. The
      present study evaluated whether a null mutation of FMR1 disrupts the patterns of
      localization of three mRNAs that are present constitutively in dendrites (the
      mRNAs for MAP2, CAMII kinase and dendrin), or disrupt the rapid dendritic
      transport of the mRNA for activity-regulated cytoskeletal protein (ARC), coded
      for by an immediate-early gene. In situ hybridization analyses revealed that the
      patterns of mRNA localization in dendrites and the dendritic transport of ARC
      mRNA are indistinguishable from normal in FMR1 knockout mice. These results
      indicate that FMRP does not play an obligatory role in targeting this set of
      mRNAs to dendrites, although it might be involved in targeting other dendritic
      mRNAs yet to be identified.

PMID- 9512394
TI  - CSF cholinesterase activity in demented and non-demented subjects.
AB  - Samples of cerebrospinal fluid (CSF) were examined, looking mainly at total
      cholinesterase (ChE) and acetyl-cholinesterase (AChE) levels from 139 living
      subjects. At the completion of the study, 35 of the 139 patients had died and
      pathological confirmation of the presence of dementia had been obtained. These
      results, together with results from other laboratories, provide evidence that a
      low CSF ChE level presenting in demented patients may indicate a depletion of the
      brain AChE system, and this may confirm a clinical diagnosis of AD as well as
      other types of dementia which are associated with an alteration of the brain AChE
      system. The overlap in the levels of CSF biochemical markers between demented and
      non-demented subjects which has led to many conflicting reports has always
      disappointed investigators. It is suggested that some 'control' subjects with CSF
      ChE activity indistinguishable from that in AD patients may have an abnormal
      ageing process in their brains (brain at risk), although the symptoms of dementia
      have not yet been detected. Recognition of a pre-clinical or incubation period is
      very beneficial for explaining discrepancies in biochemistry and pathology in the
      literature, and must be considered for both the treatment and the prevention of
      dementia. The long used treatment, which was designed to inhibit AChE, should no
      longer be used: treatment must be designed to enhance the activity of the
      neuronal AChE system, or slow its degeneration.

PMID- 9512395
TI  - Central nervous system DNA fragmentation induced by the inhibition of nuclear
      factor kappa B.
AB  - Ageing of the central nervous system (CNS) is characterized by a progressive
      apoptotic loss of neurons that may be in part due to impaired neurotrophin
      signaling mediated by such elements as the transcription factor nuclear factor
      kappa B (NFkappaB). To support this hypothesis, we inhibited nuclear
      translocation of NFkappaB in vivo by injecting a proteasome inhibitor (PSI)
      directly in the CNS lateral ventricle of rats and then measured fragmented DNA in
      various CNS areas as an index of ongoing apoptosis. Our results show that after
      PSI injection there was a significant inhibition of NFkappaB activity in vivo
      that resulted in the appearance of fragmented (apoptotic) DNA in the CNS of rats.
      These results suggest that alteration of NFkappaB may cause apoptotic cell death
      in the rat CNS during ageing.

PMID- 9512396
TI  - Temporal constraints of auditory event synthesis: evidence from ERPs.
AB  - The temporal constraints of auditory event synthesis were investigated using
      event-related potentials. Standard stimuli consisted of an initial constant
      frequency segment followed by a frequency glide. Occasionally, stimuli deviating
      from this standard both in intensity and within the direction of the glide were
      presented in the otherwise repetitive sound sequence. Previous results suggested
      that such 'double' deviants elicit only a single mismatch negativity (MMN) if the
      two temporally separate deviant elements were integrated within a common unit.
      Two successive MMNs were elicited by double deviants when the initial constant
      frequency segment of the sound was 250 ms long, but only one when this segment
      was 150 ms in duration. The results support the hypothesis that the auditory
      input is processed in approximately 200 ms long temporal integration windows.

PMID- 9512397
TI  - Tactile stimulation during finger opposition does not contribute to 3D fMRI brain
      activity pattern.
AB  - Functional magnetic resonance imaging (fMRI) is a new, non-invasive technique to
      localize brain activity with a high spatial resolution. Activation of the motor
      cortex by sequential movement of the thumb to the fingers has been used
      extensively to validate the fMRI technique. This task, however, combines motor
      activity (movement of thumb and fingers) with tactile stimulation (touching the
      finger with the thumb). In this study we examined the contribution of tactile
      stimulation to the activity pattern. Nine healthy subjects were instructed to
      touch the fingers with the thumb in a first task, and repeat this movement
      without touching the fingers in a second task. Comparison of the two activity
      patterns did not result in a significant difference. Therefore we concluded that
      the pattern of activity associated with a fingertapping task is not influenced by
      tactile stimulation, but is caused primarily by motor activation and possibly by
      proprioceptive activity.

PMID- 9512398
TI  - Differential distribution of TRP Ca2+ channel isoforms in mouse brain.
AB  - Mammalian homologues of the Drosophila TRP proteins, which are essential for
      light-activated, phosphatidyl-inositide (PI)-dependent Ca2+ conductance in
      Drosophila photoreceptors, were molecularly identified, to investigate receptor
      activated Ca2+ influx in the mammalian nervous system. Two cloned mouse TRP
      homologues, TRP3 and TRP4, structurally related to the voltage-dependent Na+
      channel, were expressed predominantly in the brain, where a sharp contrast in the
      distribution of the RNA transcripts for TRP isoforms was demonstrated by in situ
      hybridization analysis. TRP3 mRNA was concentrated in cerebellar Purkinje cells
      and sparsely localized in the cerebellar granule layer, pontine nuclei, and
      thalamus, whereas TRP4 mRNA was abundantly expressed in hippocampal CA1 pyramidal
      neurons, dentate gyrus granule cells, and cerebral cortical neurons, and in the
      septal nuclei and the mitral layer of olfactory bulb. The distinct spatial
      patterns of TRP isoforms implicate that neurons are highly heterogeneous in
      receptor-activated Ca2+ influx responsible for the second phase of PI-mediated
      rise in intracellular Ca2+.

PMID- 9512399
TI  - Excitability increase in withdrawal interneurons after conditioning in snail.
AB  - Membrane mechanisms of conditioning of the defensive reflex in the snails Helix
      pomatia and H. lucorum were investigated. Tapping on the shell was used as a
      conditioned stimulus, which under normal conditions produces no defensive
      reaction. A light blow of air into the pneumostome, called the defensive closure
      reaction, was used as an unconditioned stimulus. When a combination of
      conditioned and unconditioned stimuli were presented with 2-4 min interval, the
      reflex developed over a period of 3 days. The separate conditioned and
      unconditioned stimuli presented randomly were used as an active control. The
      electrical characteristics of identified interneurons involved in this defensive
      behavior were then measured in an isolated preparation. There was shown to be a
      decrease in the threshold of action potential generation from 20.5 to 16.3 mV and
      depolarizing shift of membrane potential from -62.1 to -57.0 mV. The electrical
      characteristics of withdrawal interneurons of active control snails did not
      differ from those in intact animals. All results show an increase in excitability
      of withdrawal interneurons after associative learning.

PMID- 9512400
TI  - Localization of the somatostatin sst2(a) receptor in human cerebral cortex,
      hippocampus and cerebellum.
AB  - The distribution and cellular localization of the somatostatin sst2(a) receptor
      was investigated in selected human brain areas using an anti-peptide antibody
      raised against a carboxy-terminal portion of the receptor protein. The sst2(a)
      receptor was found to be present on neurones and processes in the deep layers of
      the cerebral cortex, in the subicular complex and the hippocampal formation.
      Further signals were obtained in the molecular and granular layer of the
      cerebellum, with occasional weakly stained Purkinje cells. The regional
      distribution of the receptor protein was compared with quantitative
      autoradiography using a sst2 receptor selective ligand [125I]BIM23027.

PMID- 9512401
TI  - Oxidized lipoproteins activate NF-kappaB binding activity and apoptosis in PC12
      cells.
AB  - Oxidative stress in the central nervous system may cause oxidation of
      lipoproteins. The oxidized lipoproteins may in turn damage cellular and
      subcellular membranes and other biomolecules, leading to tissue injury and cell
      death. Recently, we have demonstrated that oxidized LDL and VLDL induced cell
      death in a dose-dependent manner. The present study examined the possible signal
      transduction cascade leading to cell death by oxLDL and oxVLDL in PC12 cells.
      Using the electrophoretic mobility shift assay, we found that both oxLDL and
      oxVLDL activated the binding of NF-kappaB to the consensus sequence in the
      promoter region of the target genes, followed by apopototic cell death.
      Resveratrol protects the cells from both the activation of NF-kappa-B/ DNA
      binding activity and apoptotic cell death. Results indicated that oxidized
      lipoproteins may serve as an oxidative mediator and may activate apoptosis
      through a nuclear signalling pathway contributing to the pathology in Alzheimer's
      disease.

PMID- 9512402
TI  - Post-ischemic changes in the expression of Alzheimer's APP isoforms in rat
      cerebral cortex.
AB  - A significant porportion (25%) of patients with Alzheimer's disease (AD) also
      shows vascular pathology. Recent ultrastructural studies demonstrated
      characteristic and extensive angio-architectural distortions of cerebral
      capillaries in AD brains. We examined the expression of APP mRNA isoforms of
      cerebral cortex after transient ischemia by middle cerebral artery occlusion,
      using RT-PCR. Neuronal damage and glial fibrillary acidic protein
      immunohistochemistry were also examined histologically. After transient ischemia,
      the Kunitz protease inhibitor-bearing isoforms (KPI-APP) were increased whereas
      APP 695, which lacks KPI domain, was decreased. Neuronal damage and GFAP
      immunoreactive astrocytes were also observed. These results show that focal,
      transient ischemia alters KPI-APP/APP 695 ratio in cerebral cortex and this shift
      in APP isoforms could be related to neurodegeneration and/or activation of
      astrocytes during the ischemic process.

PMID- 9512403
TI  - Amyloid beta protein increases Ca2+ currents in rat cerebellar granule neurones.
AB  - The effects of amyloid beta protein on voltage-sensitive Ca2+ channels were
      measured in cultured rat cerebellar granule neurones using the whole-cell patch
      clamp technique. Incubation of cells for 24 h with 1 microM amyloid beta protein
      resulted in a 40-60% increase in the Ca2+ channel current at potentials positive
      to 0 mV. The increase in current was accompanied by a 5 mV shift in channel
      activation in the positive direction and an increase in the rate of channel
      deactivation. Inhibition of L-type channels with 2 microM nifedipine did not
      prevent the rise in Ca2+ channel current or effects on current activation and
      deactivation. The N-type Ca2+ channel antagonist omega-conotoxin GVIA (1 microM)
      abolished the current increase and increase in the rate of channel deactivation
      but did not prevent the shift in the current activation curve. These data suggest
      that amyloid beta protein may exert its effects on cell survival by increasing
      Ca2+ influx through N-type Ca2+ channels in central neurones.

PMID- 9512404
TI  - Chronic cognitive deficits and amyloid precursor protein elevation after
      selective immunotoxin lesions of the basal forebrain cholinergic system.
AB  - Alzheimer's disease (AD) is the most common neurodegenerative disorder that
      causes cognitive deficits in the elderly. Its neuropathology is characterized by
      amyloid deposition and specific cholinergic degeneration. To address the link
      between amyloid formation and cholinergic loss, we examined histologically the
      amyloid precursor protein (APP) changes following selective immunolesion of the
      basal forebrain cholinergic system with 192 IgG-saporin in rats at 6 months post
      lesion. In such rats with cognitive deficits observed in Morris water maze tests,
      we found increased levels of APP by optical density measurements in regions of
      cholinergic denervation. APP elevation and performance in the water maze task
      correlate with reduction of acetyl-cholinesterase (AChE) activity in the frontal
      cortex and CA3 subfield of hippocampus. The data indicate that loss of
      cholinergic innervation can affect APP expression.

PMID- 9512405
TI  - Oral administration of a nonimmunosuppressant FKBP-12 ligand speeds nerve
      regeneration.
AB  - We recently showed that s.c. injections of a nonimmunosuppressant FK506 binding
      protein-12 (FKBP-12) ligand (V-10,367) accelerates nerve regeneration in the rat
      sciatic nerve crush model. Here we examined the oral efficacy of this compound
      for speeding nerve regeneration. Rats receiving V-10,367 (5, 15 or 50 mg/kg/day)
      by oral gavage all demonstrated an increase in nerve regeneration compared to
      vehicle-treated controls. Functional recovery was observed earliest and axonal
      calibers of regenerating axons in the soleus nerve were largest in the 15 mg/kg
      group, mean axonal areas being increased by 66% compared to controls. Orally
      active nonimmunosuppressant FKBP-12 ligands may be useful for the treatment of
      human peripheral nerve disorders.

PMID- 9512406
TI  - Deleterious Ca-independent NOS activity after oxidative stress in rat striatum.
AB  - The aim of this study was to assess whether oxidative stress induces deleterious
      NOS activity in the central nervous system (CNS). For this purpose, the
      mitochondrial toxin malonate, which promotes free radical production, was infused
      into the left striatum of rats. Forty-eight hours after injection, an increase in
      Ca-independent NOS activity was observed in the injected striatum. This increase
      was blocked by alpha-phenyl-tert-butyl-nitrone, a free radical scavenger, and by
      aminoguanidine, an inhibitor of NOS 2. Both these drugs reduced the malonate
      induced striatal necrotic volume. These results suggest that in the CNS oxidative
      stress can induce a Ca-independent NOS, probably of type 2, which contributes to
      the lesion.

PMID- 9512407
TI  - Microtubule dynamics: if you need a shrink try stathmin/Op18.
AB  - Recent studies show that stathmin/Op18 may be an important physiological
      regulator of microtubule dynamics; the activity of stathmin/Op18 is controlled by
      the actions of several signalling pathways, allowing it to play a central role in
      coordinating microtubule behaviour.

PMID- 9512408
TI  - The genetics of epigenetics.
AB  - The formation of silent epialleles is accompanied by local hypermethylation of
      the DNA template, and genetically altered, methylation-deficient Arabidopsis
      mutants generate an increased number of epimutations. But what came first -
      methylation or epigenetic change?

PMID- 9512409
TI  - Chloroplast biogenesis: mixing the prokaryotic and the eukaryotic?
AB  - Chloroplast biogenesis requires the translocation of proteins across the outer
      and inner envelopes. The membrane components of this transport machinery
      completely differ from those of other organelles, but recently homologues of some
      of the components have been detected in prokaryotes.

PMID- 9512410
TI  - Cytokinesis: IQGAPs find a function.

PMID- 9512411
TI  - Cellular senescence: lessons from yeast for human aging?
AB  - Recent results point to an important role for the nucleolus in the senescence of
      yeast cells. A further report suggests that the formation and preferential
      accumulation in mother cells of extrachromosomal rDNA circles is a cause of aging
      in yeast; this may be an ancient and conserved mechanism of senescence.

PMID- 9512412
TI  - Epstein-Barr virus: LMP1 masquerades as an active receptor.
AB  - The Epstein-Barr virus protein LMP1 is essential for transformation of resting B
      cells by the virus, but how it works is unclear. Recent results suggest that LMP1
      acts as a constitutively active receptor that shares certain characteristics with
      members of the tumour necrosis factor receptor superfamily.

PMID- 9512413
TI  - Plant genes: the genetics of epigenetics.
AB  - The formation of silent epialleles is accompanied by local hypermethylation of
      the DNA template, and genetically altered, methylation-deficient Arabidopsis
      mutants generate an increased number of epimutations. But what came first-
      methylation or epigenetic change?

PMID- 9512414
TI  - Archaeal genomics: do archaea have a mixed heritage?
AB  - A third complete archaeal genome sequence, replete with eukaryote-like genes for
      replication, transcription and translation, has appeared. The sequence also shows
      bacteria-like features. It is time to come to grips with this evidence for a
      mixed heritage.

PMID- 9512415
TI  - NF-protocadherin, a novel member of the cadherin superfamily, is required for
      Xenopus ectodermal differentiation.
AB  - BACKGROUND: The assembly of complex tissues during embryonic development is
      thought to depend on differential cell adhesion, mediated in part by the cadherin
      family of cell-adhesion molecules. The protocadherins are a new subfamily of
      cadherins; their extracellular domains comprise cadherin-like repeats but their
      intracellular domains differ significantly from those of classical cadherins.
      Little is known about the ability of protocadherins to mediate the adhesion of
      embryonic cells, or whether they play a role in the formation of embryonic
      tissues. RESULTS: We report the isolation and characterization of a novel
      protocadherin, termed NF-protocadherin (NFPC), that is expressed in Xenopus
      embryos. NFPC showed a striking pattern of expression in early embryos,
      displaying predominant expression within the deep, sensorial layer of the
      embryonic ectoderm and in a restricted group of cells in the neural folds, but
      was largely absent from the neural plate and surrounding placodal regions.
      Ectopic expression in embryos demonstrated that NFPC could mediate cell adhesion
      within the embryonic ectoderm. In addition, expression of a dominant-negative
      form of NFPC disrupted the integrity of embryonic ectoderm, causing cells in the
      deep layer to dissociate, though leaving the outer layer relatively intact.
      CONCLUSIONS: Our results indicate that NFPC is required as a cell-adhesion
      molecule during embryonic development, and its function is distinct from that of
      classical cadherins in governing the formation of a two-layer ectoderm. These
      results suggest that NFPC, and protocadherins in general, are involved in novel
      cell-cell adhesion mechanisms that play important roles in tissue histogenesis.

PMID- 9512416
TI  - A higher plant seven-transmembrane receptor that influences sensitivity to
      cytokinins.
AB  - BACKGROUND: All organisms perceive and respond to a profusion of environmental
      and endogenous signals that influence growth, development and behavior. The G
      protein signalling pathway is a highly conserved mechanism for transducing
      extracellular signals, and the superfamily of receptors that have seven
      transmembrane (7TM) domains is a primary element of this pathway. Evidence that
      heterotrimeric G proteins are involved in signal transduction in plants is
      accumulating, prompting speculation that plant 7TM receptors might exist.
      RESULTS: Using information in the dbEST database of expressed sequence tags, we
      isolated an Arabidopsis thaliana gene (GCR1) that encodes a protein with seven
      predicted membrane-spanning domains and other features characteristic of 7TM
      receptors. The protein shows 18-23% amino-acid identity (46-53% similarity) to,
      and good colinear alignment with, 7TM receptors from three different families.
      Its highest sequence identity is with the Dictyostelium cAMP receptors. GCR1 is
      expressed at very low levels in the roots, stems and leaves of Arabidopsis; it is
      a single-copy gene which maps close to the restriction fragment length
      polymorphism marker m291 on chromosome 5. Transgenic Arabidopsis expressing
      antisense GCR1 under the control of the constitutive cauliflower mosaic virus 35S
      promoter have reduced sensitivity to cytokinins in roots and shoots, yet respond
      normally to all other plant hormones. This suggests a functional role for GCR1 in
      cytokinin signal transduction. CONCLUSIONS: GCR1 encodes the first 7TM receptor
      homologue identified in higher plants and is involved in cytokinin signal
      transduction. This discovery suggests that 7TM receptors are ancient and predate
      the divergence of plants and animals.

PMID- 9512417
TI  - Identification of a nuclear export receptor for tRNA.
AB  - BACKGROUND: Transport of macromolecules between the nucleus and cytoplasm of
      eukaryotic cells is mediated by nuclear import and export receptors. The
      receptors identified to date are members of a family of Ran GTPase-binding
      proteins whose founding member is importin-beta. Interaction between these
      receptors and their cargo is regulated by the GTP-bound form of Ran. Export
      complexes form and import complexes disassemble on binding of RanGTP to the
      receptor. Yeast Los 1 p is a member of the importin-beta family with a poorly
      defined role in tRNA production. RESULTS: A human member of the importin-beta
      family that is distantly related to Los 1 p (21% identity) has been
      characterized. The protein shuttled between the nucleus and cytoplasm and
      interacts with tRNA in a RanGTP-dependent manner. Injection of the protein into
      the nuclei of Xenopus oocytes resulted in a specific stimulation of the export of
      tRNA from the nucleus and in relief of the competitive inhibition of tRNA export
      caused by the introduction of saturating amounts of nuclear tRNA. CONCLUSIONS:
      The human protein has the functional properties expected of a transport receptor
      that mediates export of tRNA from the nucleus. We therefore name the protein
      Exportin(tRNA).

PMID- 9512418
TI  - Developmental regulation of MCM replication factors in Xenopus laevis.
AB  - At the midblastula transition (MBT) during Xenopus laevis development, zygotic
      transcription begins [1], and the rapid, early cleavage cycles are replaced by
      cell-division cycles that lengthen and acquire G (gap) phases [2] and checkpoints
      [3-5]. This cell-cycle remodeling may result from either a loss of maternal
      products, the transcription of zygotic genes, or the replacement of maternal
      proteins by zygotic gene products. We have identified an example of the third
      possibility: distinct maternal and zygotic genes encoding a member of the
      minichromosome maintenance (MCM) protein family. The mcm genes were identified in
      yeast by mutations that blocked replication of artificial chromosomes or
      perturbed the G1/S transition in the cell cycle [6,7]. In Xenopus eggs, the MCM2
      MCM7 proteins assemble as multimeric complexes at chromosomal origins of
      replication [8-14]. The sequential, cell-cycle-dependent assembly of the origin
      replication complex (ORC), CDC6 protein and the MCM complex at origins of
      replication ensures that DNA replicates only once per cell cycle [15,16]. The
      periodic association of the MCM complex with chromatin may be regulated via
      phosphorylation by cyclin-dependent kinases (Cdks) [11]. We have cloned the first
      example of a developmentally regulated mcm gene, zygotic mcm6 (zmcm6), expressed
      only after gastrulation when the cell cycle is remodeled. The zMCM6 protein
      assembles into MCM complexes and differs from maternal MCM6 (mMCM6) in having a
      carboxy-terminal extension and a consensus cyclin-Cdk phosphorylation site. There
      may also be maternal-zygotic pairs of other MCMs. These data suggest that MCMs
      are critical for cell-cycle remodeling during early Xenopus development.

PMID- 9512419
TI  - Inhibitors of cyclin-dependent kinases induce features of replicative senescence
      in early passage human diploid fibroblasts.
AB  - After a limited number of population doublings (PDs), cultures of normal
      mammalian diploid cells undergo an irreversible growth arrest known as
      replicative senescence [1]. As well as contributing to cellular ageing,
      senescence is viewed as an important mechanism of tumour suppression by
      preventing the emergence of immortal cell clones [2-4]. Senescent cells have a
      number of characteristics that distinguish them from cycling or quiescent cells
      including elevated levels of two cyclin-dependent kinase (Cdk) inhibitors,
      p16INK4a and p21CIP1 [5-11]. Here, we demonstrate that both of these Cdk
      inhibitors, as well as other members of their protein families (the INK4 and
      CIP/KIP families, respectively [12]), induce several facets of the senescent
      phenotype when ectopically expressed in young human diploid fibroblasts. These
      include a reduced proliferative capacity, an altered size and shape, the presence
      of underphosphorylated retinoblastoma protein (pRb), increased expression of
      plasminogen activator inhibitor (PAI-1) and the appearance of senescence
      associated beta-galactosidase (SA-beta-gal) activity [2,3,13-15]. A 20 amino acid
      peptide from p16INK4a that inhibits Cdks active in the G1 phase of the cell cycle
      [16] produces similar effects in a dose-dependent manner suggesting that, in
      primary fibroblasts, inhibition of G1-specific Cdk activity is sufficient to
      induce phenotypic changes that normally occur at the end of their finite
      lifespan.

PMID- 9512420
TI  - Receptor-induced transient reduction in plasma membrane PtdIns(4,5)P2
      concentration monitored in living cells.
AB  - Although phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) is a well
      characterized precursor for the second messengers inositol 1,4,5-trisphosphate,
      diacylglycerol [1] and phosphatidylinositol 3,4,5-trisphosphate [2], it also
      interacts with the actin-binding proteins profilin and gelsolin [3], as well as
      with many signaling molecules that contain pleckstrin homology (PH) domains [4].
      It is conceivable that stimuli received by receptors in the plasma membrane could
      be sufficiently strong to decrease the PtdIns(4,5)P2 concentration; this decrease
      could alter the structure of the cortical cytoskeleton and modulate the activity
      of signaling molecules that have PH domains. Here, we tested this hypothesis by
      using an in vivo fluorescent indicator for PtdIns(4,5)P2, by tagging the PH
      domain of phospholipase C delta 1 (PLC-delta 1) with the green fluorescent
      protein (GFP-PH). When expressed in cells, GFP-PH was found to be enriched at the
      plasma membrane. Binding studies in vitro and mutant analysis suggested that GFP
      PH bound PtdIns(4,5)P2 selectively over other phosphatidylinositol lipids.
      Strikingly, receptor stimulation induced a transient dissociation of GFP-PH from
      the plasma membrane, suggesting that the concentration of PtdIns(4,5)P2 in the
      plasma membrane was effectively lowered. This transient dissociation was blocked
      by the PLC inhibitor U73122 but was not affected by the phosphoinositide (PI) 3
      kinase inhibitor wortmannin, suggesting that it is mostly mediated by PLC and not
      by PI 3-kinase activation. Overall, our studies show that PtdIns(4,5)P2 can have
      second messenger functions of its own, by mediating a transient dissociation of
      proteins anchored in the plasma membrane.

PMID- 9512421
TI  - A distinct role for interleukin-13 in Th2-cell-mediated immune responses.
AB  - Immune responses elicited by allergic reactions and parasitic worm infections are
      characterised by the induction of T helper 2 (Th2) cells. These cells secrete
      cytokines such as interleukin-4 (IL-4), IL-5 and IL-13, which induce the
      production of immunoglobulin E (IgE) and eosinophils [1,2]. Previous studies
      using gastrointestinal nematodes to elucidate the role of Th2-cell-mediated
      immune responses have demonstrated a causal relationship between T cells and worm
      expulsion (reviewed in [3]). Although it has been proposed that IL-4 played a
      central role in these responses, recent studies demonstrated that IL-4-/- mice
      expel the parasitic gastrointestinal nematode Nippostrongylus brasiliensis
      normally [4], suggesting that another T-cell mediator is required for efficient
      worm clearance. Using IL-13-/- mice, we have demonstrated that, unlike wild-type
      and IL-4-/- mice, the IL-13-/- animals failed to clear N. brasiliensis infections
      efficiently, despite developing a robust Th2-like cytokine response to infection.
      Furthermore, treatment of the IL-13-/- mice with exogenous IL-13 resulted in a
      reduction in the numbers of worms recovered. The IL-13-/- animals also failed to
      generate the goblet cell hyperplasia that normally occurs coincident with worm
      expulsion. This observation may link IL-13 with the production of intestinal
      mucus which is believed to facilitate worm expulsion. These data support a unique
      role for IL-13 in Th2-cell-mediated immune responses and demonstrate that IL-13
      and IL-4 are not redundant.

PMID- 9512422
TI  - Antigen-specific release of beta-chemokines by anti-HIV-1 cytotoxic T
      lymphocytes.
AB  - A major advance in understanding human immunodeficiency virus (HIV) biology was
      the discovery that the beta-chemokines MIP-1 alpha (macrophage inflammatory
      protein-1 alpha), MIP-1 beta (macrophage inflammatory protein-1 beta) and RANTES
      (regulated on activation, normal T-cell expressed and secreted) inhibit entry of
      HIV-1 into CD4+ cells by blocking the critical interaction between the CCR5
      coreceptor and the V3 domain of the viral envelope glycoprotein gp120 [1,2]. CD8+
      lymphocytes are a major source of beta-chemokines [3], but the stimulus for
      chemokine release has not been well defined. Here, we have shown that engagement
      of CD8+ cytotoxic T lymphocytes (CTLs) with HIV-1-encoded human leukocyte antigen
      (HLA) class I-restricted peptide antigens caused rapid and specific release of
      these beta-chemokines. This release paralleled cytolytic activity and could be
      attenuated by naturally occurring amino acid variation within the HLA class I
      restricted peptide sequence. Epitope variants that bound to appropriate HLA class
      I molecules but failed to stimulate cytolytic activity in CTLs also failed to
      stimulate chemokine release. We conclude that signalling through the T-cell
      receptor (TCR) following binding of antigen results in beta-chemokine release
      from CTLs in addition to cytolytic activity, and that both responses can be
      abolished by epitope mutation. These results suggest that antigenic variation
      within HIV-1 might not only allow the host cell to escape lysis, but might also
      contribute to the propagation of infection by failing to activate beta-chemokine
      mediated inhibition of HIV-1 entry.

PMID- 9512423
TI  - The crystal structure of a complement-1q family protein suggests an evolutionary
      link to tumor necrosis factor.
AB  - ACRP30--adipocyte complement-related protein of 30 kDa or AdipoQ--is an abundant
      serum protein, secreted exclusively from fat cells, which is implicated in energy
      homeostasis and obesity [1,2]. ACRP30 is a close homologue of the complement
      protein C1q, which is involved in the recognition of microbial surfaces [3-5] and
      antibody-antigen complexes [6,7] in the classical pathway of complement. We have
      determined the crystal structure of a homotrimeric fragment from ACRP30 at 2.1 A
      resolution. The structure reveals an unexpected homology to the tumor necrosis
      factor (TNF) family. Identical folding topologies, key residue conservations, and
      similarity of trimer interfaces and intron positions firmly establish an
      evolutionary link between the TNF and C1q families. We suggest that TNFs--which
      control many aspects of inflammation, adaptive immunity, apoptosis and energy
      homeostasis--arose by divergence from a primordial recognition molecule of the
      innate immune system. The evolutionary connection between C1q-like proteins and
      TNFs illuminates the shared functions of these two important groups of proteins.

PMID- 9512424
TI  - MADD is highly homologous to a Rab3 guanine-nucleotide exchange protein (Rab3
      GEP)

PMID- 9512425
TI  - Mike Dexter: a welcome appointment

PMID- 9512427
TI  - Broadening your horizons

PMID- 9512426
TI  - Parchment-skin illusion: sound-biased touch.

PMID- 9512435
TI  - Introduction to the Conference on Beryllium-related Diseases

PMID- 9512453
TI  - Use of genetically engineered mice as models for exploring the role of oxidative
      stress in neurodegenerative diseases.
AB  - A growing body of evidence has suggested that oxidative stress may play a major
      role in the degeneration of neurons associated with several neurological diseases
      of aging including ALS, Parkinson's, and Alzheimer's disease; this has been the
      topic of numerous previous reviews and opinion papers (e.g. 1-10). The ability to
      construct genetically engineered mouse lines containing targeted mutations has
      done much to aid in the assessment of the role of reactive oxygen species (ROS)
      in both the initiation as well as the progression of these diseases and has
      markedly advanced research in the field. Most importantly, the creation of
      genetic animal models has strengthened the argument that antioxidants may be a
      useful therapy in the treatment of these types of disorders.

PMID- 9512454
TI  - Signal transduction during apoptosis; implications for cancer therapy.
AB  - Programmed cell death is a fundamental aspect of organismal development and
      stasis through its role in the maintenance of the balance between cell growth and
      cell death. If the balance is tipped, e.g. by unregulated cell growth, the result
      can be cancer. If tipped the other direction, e.g. by dysregulated cell death,
      and the result can again be cancer. The concept of dysregulated cell death, which
      until recently was not considered by oncologists, has forced a shift in the
      paradigm of cancer development. Along with this shift in thinking comes the
      likelihood that radiation and chemotherapy, both major modalities of cancer
      therapy, can benefit from strategies that modulate programmed cell death. One
      form of programmed cell death that is distinguished by its morphological features
      is called apoptosis. This form of programmed cell death is an energy dependent
      biochemically regulated process that is contingent upon a set of factors: the
      initial stimulatory event or in some cases a cellular insult, the organism, the
      cell type, the cellular environment, and other factors. This biochemical process
      is the result of the expression of a number of genes. In this review, the roles
      of several genes and gene families considered to be critical to the signal
      transduction cascade of apoptosis are described. Growth factors and cytokines are
      also discussed in the context of their interaction with these genes. We also
      discuss how these genes and their protein products are being used as prognostic
      indicators for cancer and cancer therapy and/or how they are the focus of
      strategies that either cause apoptosis or alter a cancer cell's propensity to
      initiate apoptosis when insulted by chemotherapy agents or radiation in the
      course of cancer therapy.

PMID- 9512456
TI  - The novel endogenous cannabinoid 2-arachidonoylglycerol is inactivated by
      neuronal- and basophil-like cells: connections with anandamide.
AB  - The novel endogenous cannabinoid 2-arachidonoylglycerol (2-AG) was rapidly
      inactivated by intact rat basophilic leukaemia (RBL-2H3) and mouse neuroblastoma
      (N18TG2) cells through diffusion/hydrolysis/reacylation processes. The hydrolysis
      of 2-AG was inhibited by typical esterase inhibitors and by more specific
      blockers of 'fatty acid amide hydrolase' (FAAH), the enzyme catalysing the
      hydrolysis of the other 'endocannabinoid', anandamide (AEA). No evidence for a
      facilitated-diffusion process was found. A 2-AG-hydrolysing activity was detected
      in homogenates from both cell lines, with the highest levels in membrane
      fractions. It exhibited an optimal pH at 10, and recognized both 2- and 1(3)-
      isomers of monoarachidonoylglycerol with similar efficiencies. The apparent Km
      and Vmax values for -3H-2-AG hydrolysis were 91 microM and 29 microM and 2.4 and
      1.8 nmol.min-1.mg of protein-1 respectively in N18TG2 and RBL-2H3 cells. [3H]2-AG
      hydrolysis was inhibited by Cu2+, Zn2+ and p-hydroxymercuribenzoate, and by 2- or
      1(3)-monolinoleoyl- and -linolenoyl-glycerols, but not by the oleoyl, palmitoyl
      and myristoyl congeners. Purified fractions from solubilized membrane proteins
      catalysed, at pH 9.5, the hydrolysis of 2-AG as well as AEA. Accordingly, AEA as
      well as FAAH inhibitors, including arachidonoyltrifluoromethyl ketone (ATFMK),
      blocked [3H]2-AG hydrolysis by N18TG2 and RBL-2H3 membranes, whereas 2-AG
      inhibited [14C]AEA hydrolysis. FAAH blockade by ATFMK preserved from inactivation
      the 2-AG synthesized de novo by intact N18TG2 cells stimulated with ionomycin.
      These data suggest that FAAH may be one of the enzymes deputed to the
      physiological inactivation of 2-AG, and create intriguing possibilities for the
      cross-regulation of 2-AG and AEA levels.

PMID- 9512457
TI  - Redox regulation of cAMP levels by ascorbate in 1,25-dihydroxy- vitamin D3
      induced differentiation of HL-60 cells.
AB  - 1alpha,25-Dihydroxyvitamin D3 [1,25-(OH)2D3] induces differentiation to monocyte
      macrophage lineage of several leukaemic cell lines such as HL-60, U937, M1 and
      Mono Mac 6. Ascorbate also modulates growth and differentiation of different
      animal cells in culture. We have previously reported the stimulating effect of
      ascorbate on 1, 25-(OH)2D3-induced HL-60 cell differentiation. We show here that
      1, 25-(OH)2D3 induces a transient increase in cAMP levels in these cells, and
      ascorbate significantly increases these cAMP levels. Ascorbate alone does not
      have any effect. Other cAMP-increasing agents such as isobutylmethylxanthine,
      forskolin and prostaglandin E2 maintain high levels of cAMP at 48 h of incubation
      and also enhance differentiation along the monocytic pathway induced by 1, 25
      (OH)2D3, as revealed by specific differentiation markers, demonstrating the
      importance of cAMP in the differentiation process. It is also shown that the
      presence of ascorbate and its free radical (AFR) during 1,25-(OH)2D3-induced
      differentiation significantly decreases cytoplasmic NADH levels compared with
      those induced by 1,25-(OH)2D3 in HL-60 cells. The results indicate that NADH is
      an inhibitor of adenylate cyclase in these cells. AFR is an electron acceptor of
      the trans-plasma-membrane electron-transport system, and NADH is the electron
      donor. Through this system, ascorbate and AFR keep levels of NADH low, thereby
      decreasing its inhibitory effect on adenylate cyclase activity and so increasing
      cAMP synthesis. We also demonstrate that other ascorbate derivatives, such as
      ascorbate 2-phosphate and dehydroascorbate, both of which are unable to produce
      AFR, do not alter intracellular NADH levels during 1, 25-(OH)2D3-induced
      differentiation. Also, ascorbate and AFR increase specific differentiation
      markers (CD14 and NitroBlue Tetrazolium reduction) but neither ascorbate 2
      phosphate nor dehydroascorbate show this enhancing activity. In summary, we
      propose that the effect of ascorbate on 1,25-(OH)2D3-induced differentiation of
      HL-60 cells can be explained by redox regulation of the cAMP pathway.

PMID- 9512455
TI  - Transcriptional control and the role of silencers in transcriptional regulation
      in eukaryotes.
AB  - Mechanisms controlling transcription and its regulation are fundamental to our
      understanding of molecular biology and, ultimately, cellular biology. Our
      knowledge of transcription initiation and integral factors such as RNA polymerase
      is considerable, and more recently our understanding of the involvement of
      enhancers and complexes such as holoenzyme and mediator has increased
      dramatically. However, an understanding of transcriptional repression is also
      essential for a complete understanding of promoter structure and the regulation
      of gene expression. Transcriptional repression in eukaryotes is achieved through
      'silencers', of which there are two types, namely 'silencer elements' and
      'negative regulatory elements' (NREs). Silencer elements are classical, position
      independent elements that direct an active repression mechanism, and NREs are
      position-dependent elements that direct a passive repression mechanism. In
      addition, 'repressors' are DNA-binding trasncription factors that interact
      directly with silencers. A review of the recent literature reveals that it is the
      silencer itself and its context within a given promoter, rather than the
      interacting repressor, that determines the mechanism of repression. Silencers
      form an intrinsic part of many eukaryotic promoters and, consequently, knowledge
      of their interactive role with enchancers and other transcriptional elements is
      essential for our understanding of gene regulation in eukaryotes.

PMID- 9512458
TI  - Uptake and catabolism of modified LDL in scavenger-receptor class A type I/II
      knock-out mice.
AB  - The liver is the major organ responsible for the uptake of modified low-density
      lipoprotein (LDL) from the blood circulation, with endothelial and Kupffer cells
      as major cellular uptake sites. Scavenger-receptors, which include various
      classes, are held responsible for this uptake. Mice deficient in scavenger
      receptor class A types I and II were created and the fate of acetylated LDL (Ac
      LDL) in vivo and its interaction with liver endothelial, Kupffer and peritoneal
      macrophages was characterized. Surprisingly, the decay in vivo (t12 < 2 min),
      tissue distribution and liver uptake (at 5 min it was 77.4 +/- 4.6% of the
      injected dose) of Ac-LDL in the knock-out mice were not significantly different
      from control mice (t12 < 2 min and liver uptake 79.1 +/- 4.6% of the injected
      dose). A separation of mice liver cells into parenchymal, endothelial and Kupffer
      cells 10 min after injection of Ac-LDL indicated that in both control and knock
      out mice the liver endothelial cells were responsible for more than 70% of the
      liver uptake. Both in control and knock-out mice, preinjection of polyinosinic
      acid (poly I, 200 microg) completely blocked the liver uptake, indicating that
      both in control and knock-out mice the scavenger-receptors are sensitive to poly
      I. Preinjection of suboptimal poly I concentrations (20 and 50 microg) provided
      evidence that the serum decay and liver uptake of Ac-LDL is more readily
      inhibited in the knock-out mice as compared with the control mice, indicating
      less efficient removal of Ac-LDL in vivo in the knock-out mice under these
      conditions. Studies in vitro with isolated liver endothelial and Kupffer cells
      from knock-out mice indicate that the cell association of Ac-LDL during 2 h at 37
      degrees C is 50 and 53% of the control, respectively, whereas the degradation
      reaches values of 58 and 63%. For peritoneal macrophages from knock-out mice the
      cell association of Ac-LDL was identical to the control mice whereas the Ac-LDL
      degradation in cells from the knock-out mice was 17% of the control. The low
      degradation capacity of peritoneal macrophages from knock-out mice for Ac-LDL
      indicates that scavenger-receptor class A types I and II play a quantitative
      important role in the degradation of Ac-LDL by macrophages. In liver, the
      contribution of scavenger-receptor class A types I and II to the maximal uptake
      and degradation of Ac-LDL by endothelial and Kupffer cells was 40-50%. Binding
      studies performed at 4 degrees C indicate that the lower rates of degradation are
      due to a lower number of surface receptors on the cells from the knock-out mice.
      From the in vitro and in vivo data it can be concluded that in addition to the
      classic scavenger-receptors class A types I and II liver does contain additional
      novel poly I-sensitive scavenger-receptors that facilitate efficient removal of
      Ac-LDL from the blood circulation. The availability of the scavenger-receptor
      class A types I and II knock-out mice will stimulate further molecular
      identification of these receptors.

PMID- 9512459
TI  - PAX 8 activates the enhancer of the human thyroperoxidase gene.
AB  - In this study we report on a novel natural target of the paired domain
      transcription factor PAX 8 in the enhancer element of the human thyroperoxidase
      gene, one of the most important thyroid differentiation markers. It is the
      primary enzyme involved in thyroid hormone synthesis and PAX 8 has been
      previously identified as an activating factor of the rat thyroperoxidase gene
      promoter. In vitro, PAX 8 binds a cis element of the human enhancer and its
      exogenous expression induces the enhancer activity in co-transfection experiments
      in Cos-7 cells. When mutated at this binding site, the enhancer is no longer
      activated by PAX 8. Our finding strengthens the PAX 8 role in the maintenance of
      thyroid differentiation and in particular in the tissue-specific thyroperoxidase
      gene expression.

PMID- 9512460
TI  - The C-terminus of factor H: monoclonal antibodies inhibit heparin binding and
      identify epitopes common to factor H and factor H-related proteins.
AB  - We have generated monoclonal antibodies (mAbs) specific for the C-terminus of
      factor H that can be used as inhibitory antibodies for heparin binding and for
      the specific detection of factor H and factor H-related proteins (FHRs) in plasma
      and triacylglycerol-rich lipoproteins. Four distinct mAbs were established: IXF9
      (IgG1), VD3 (IgG2a), VIG8 (IgG1) and IIC5 (IgG1). Each reacts specifically with
      FHR-1 and factor H (and also with FHR-2 in the case of VIG8), but none binds to
      the related FHR-3 and FHR-4 proteins nor to factor H-like protein 1. By the use
      of deletion mutants of factor H and by comparing the reactivity with FHR-1 and
      FHR-2, the binding epitopes of the mAbs were identified and localized to
      different short consensus repeats (SCRs): mAbs IXF9 and VD3 bind to related or
      even identical sites within SCR18 (factor H) and SCR3 (FHR-1) respectively. mAbs
      VIG8 and IIC5 bind to different epitopes located within SCRs 19 to 20 of factor H
      and SCRs 4 to 5 of FHR-1 respectively. Only mAb VIG8 reacts with the
      corresponding SCRs 3 to 4 of FHR-2. These antibodies are useful for the detection
      of the corresponding proteins in biological specimens such as fractions of
      lipoproteins. In addition, mAb VIG8 has the unique feature of inhibiting binding
      of factor H to heparin. Given the recent identification of a heparin- and a C3b
      binding domain within the C-terminus of factor H, these mAbs should provide
      useful tools for functional analysis and for the precise localization of the
      domain(s) required for this interaction.

PMID- 9512461
TI  - Evolution of alanine:glyoxylate aminotransferase intracellular targeting:
      structural and functional analysis of the guinea pig gene.
AB  - The distribution of alanine:glyoxylate aminotransferase 1 (AGT) within liver
      cells has changed many times during mammalian evolution. Depending on the
      particular species, AGT can be found in mitochondria or peroxisomes, or
      mitochondria and peroxisomes. In some cases significant cytosolic AGT is also
      present. In the livers of most rodents, AGT has what is thought to be the more
      'ancestral' distribution (i.e. mitochondrial and peroxisomal). However, AGT is
      distributed very differently in the guinea pig, being peroxisomal and cytosolic.
      In this study, we have attempted to determine the molecular basis for the loss of
      mitochondrial AGT targeting and the apparent inefficiency of peroxisomal
      targeting of AGT in the guinea pig. Our results show that the former is owing to
      the evolutionary loss of the more 5' of two potential transcription and
      translation initiation sites, resulting in the loss of the ancestral N-terminal
      mitochondrial targeting sequence from the open reading frame. Guinea pig AGT is
      targeted to peroxisomes via the peroxisomal targeting sequence type 1 (PTS1)
      peroxisomal import machinery, even though its C-terminal tripeptide, HRL,
      deviates from the standard consensus PTS1 motif. Although HRL appears to target
      AGT to peroxisomes less efficiently than the classical PTS1 SKL, the main reason
      for the low efficiency of AGT peroxisomal targeting in guinea pig cells (compared
      with cells from other species) lies not with guinea pig AGT but with some other,
      as yet undefined, part of the guinea pig peroxisomal import machinery.

PMID- 9512462
TI  - Characterization of human involucrin promoter distal regulatory region
      transcriptional activator elements-a role for Sp1 and AP1 binding sites.
AB  - Human involucrin (hINV) is an important precursor of the keratinocyte cornified
      envelope that is specifically expressed in the suprabasal layers of stratifying
      epithelia. Previous truncation and mutagenesis experiments have shown that an
      activator protein 1 (Ap1) site, AP1-5, located 2100bp upstream of the
      transcription start site, is required for optimal promoter activity. These
      previous studies suggest that AP1-5 is part of a distal regulatory region
      spanning nucleotides -2473 to -2088. In the present report, we study the distal
      regulatory region (DRR), which surrounds AP1-5. Our studies show that this region
      contains weak and strong activator elements spanning nucleotides -2473/-2216 and 
      2140/-2088, respectively. The strong activator element contains AP1-5 and an
      adjacent specificity protein 1 (Sp1) site. The AP1-5 site is absolutely required
      for DRR activity, as its mutation reduces transcription to basal levels.
      Mutagenesis studies of the AP1-5 and Sp1 sites in the presence or absence of the
      weak activator element indicate that the Sp1 site and the weak activator element
      synergistically activate the AP1-5 site-dependent transcription. The cooperation
      between the Sp1 and AP1-5 sites is also observed in the context of the full
      length promoter. Gel mobility shift and supershift studies show that Sp1, but not
      Sp2, Sp3 or Sp4 binds to the Sp1 site. When the Sp1 site is mutated or the
      distance between the AP1-5 and Sp1 site is increased, the binding of AP1 factors
      to AP1-5 is markedly reduced. Surprisingly, gel shift studies suggest that
      activation does not require the formation of a stable AP1/Sp1/DNA ternary
      complex. These studies suggest that the AP1-5 site is absolutely required for
      transcriptional activation, that the weak activator element and Sp1 sites serve
      to enhance this activation, and that the Sp1 site is required for optimal AP1
      factor binding at the AP1-5 site.

PMID- 9512463
TI  - Purification and characterization of membrane-bound semicarbazide-sensitive amine
      oxidase (SSAO) from bovine lung.
AB  - Semicarbazide-sensitive amine oxidase (SSAO) has been purified from bovine lung
      microsomes in a form which is catalytically active and stable to storage. The
      enzyme, an integral membrane protein, was solubilized with Triton X-100 and
      purification was achieved, in the presence of detergent, by chromatography with
      Cibacron Blue 3GA-agarose, hydroxylapatite, Lens culinaris-agarose, Resource Q
      FPLC and gel filtration on Superdex 200 HR-FPLC. This is the first reported
      procedure for the extensive purification of a membrane-bound SSAO. The purified
      enzyme had an apparent Mr of 400000 but exhibited microheterogeneity with
      SDS/PAGE and isoelectric focusing, probably as a result of its glycoprotein
      nature. It behaved as a tetramer with subunits with apparent Mr values of 100.
      Antibodies raised towards the purified enzyme cross-reacted with the enzymes from
      human lung and bovine plasma. Redox-cycling staining and reaction with carbonyl
      reagents were consistent with the presence of a quinone cofactor, possibly topa
      quinone. The enzyme was also shown to contain two mol of Cu/mol of enzyme and
      removal of half of this bound copper resulted essentially in complete inhibition
      of enzyme activity. In contrast to the reported behaviour of the SSAO enzymes
      from plasma, the bovine lung enzyme was relatively insensitive to inhibition by
      cyanide, copper-chelating agents and amiloride. The specificity of the bovine
      lung enzyme was also narrower than reported for soluble SSAO. It catalysed the
      oxidative deamination of benzylamine, methylamine, 2-phenylethylamine and
      histamine but had no significant activity towards dopamine, 5-hydroxytryptamine,
      tryptamine or tyramine.

PMID- 9512464
TI  - DNA polymerase beta: effects of gapped DNA substrates on dNTP specificity,
      fidelity, processivity and conformational changes.
AB  - Pre-steady-state kinetic analysis was used to compare the catalytic properties of
      DNA polymerase beta (Pol beta) for single-base gap-filling and regular duplex DNA
      synthesis. The rate of polymerization (kpol) and the apparent equilibrium
      dissociation constant of dNTP (Kd) were determined with single-nucleotide gapped
      DNA substrates for all four possible correct base pairs and twelve possible
      incorrect base pairs, and the results were compared with those obtained
      previously with non-gapped primer/template duplex DNA substrates. For correct
      dNTP incorporation, the use of single-nucleotide gapped DNA led to significant
      decreases in the Kd of dNTP. Although kpol was little affected, the catalytic
      efficiency kpol/Kd increased significantly owing to the decreases in Kd. In
      contrast, for incorrect dNTP incorporation, the use of single-nucleotide gapped
      DNA substrates did not affect the Kd of dNTP appreciably but caused the kpol (and
      thus kpol/Kd) for incorrect dNTP incorporation to increase. As a consequence the
      fidelity of Pol beta was not significantly affected by the use of single
      nucleotide gapped DNA substrates. In addition we show that under processive
      polymerization conditions the processivity of Pol beta increases in the gap
      filling synthesis owing to a decreased rate of DNA dissociation. Finally, with a
      single-nucleotide gapped DNA substrate the rate-limiting conformational change
      step before chemistry was also observed. However, the preceding fast
      conformational change observed with duplex DNA substrates was not clearly
      detected. A possible cause is that in the complex with the gapped DNA, the 8 kDa
      N-terminal domain of Pol beta already exists in a closed conformation. This
      interpretation was supported by tryptic digestion experiments.

PMID- 9512465
TI  - 3,5,3'-Tri-iodo-L-thyronine acutely regulates a protein kinase C-sensitive, Ca2+
      independent, branch of the hepatic alpha1-adrenoreceptor signalling pathway.
AB  - This work aimed to investigate the acute effect of the thyroid hormone 3,5,3'-tri
      iodo-L-thyronine (T3) in regulating the hepatic metabolism either directly or by
      controlling the responsiveness to Ca2+-mobilizing agonists. We did not detect any
      acute metabolic effect of T3 either in perfused liver or in isolated liver cells.
      However, T3 exerted a powerful inhibitory effect on the alpha1-adrenoreceptor
      mediated responses. The promptness of this T3 effect rules out that it was the
      result of rate changes in gene(s) transcription. T3 inhibited the alpha1
      adrenoreceptor-mediated sustained stimulation of respiration and release of Ca2+
      and H+, but not the glycogenolytic or gluconeogenic responses, in perfused liver.
      In isolated liver cells, T3 enhanced the alpha1-agonist-induced increase in
      cytosolic free Ca2+ and impeded the intracellular alkalinization. Since T3 also
      prevented the alpha1-adrenoreceptor-mediated activation of protein kinase C, its
      effects on pH seem to be the result of a lack of activation of the Na+/H+
      exchanger. The failure of T3 to prevent the alpha1-adrenergic stimulation of
      gluconeogenesis despite the inhibition of protein kinase C activation indicates
      that the elevation of cytosolic free Ca2+ is a sufficient signal to elicit that
      response. T3 also impaired some of the angiotensin-II-mediated responses, but did
      not alter the effects of PMA on hepatic metabolism, indicating, therefore, that
      some postreceptor event is the target for T3 actions. The differential effect of
      T3 in enhancing the alpha1-adrenoreceptor-mediated increase in cytosolic free
      Ca2+ and preventing the activation of protein kinase C, provides a unique tool
      for further investigating the role of each branch of the signalling pathway in
      controlling the hepatic functions. Moreover, the low effective concentrations of
      T3 (<= 10 nM) in perturbing the alpha1-adrenoreceptor-mediated response suggests
      its physiological significance.

PMID- 9512466
TI  - ATP-dependent transport of unconjugated bilirubin by rat liver canalicular plasma
      membrane vesicles.
AB  - The transport of highly purified 3H-labelled unconjugated bilirubin (UCB) was
      investigated in rat liver plasma membrane vesicles enriched in the canalicular
      domain and found to be stimulated (more than 5-fold) by the addition of ATP.
      Other nucleotides, such as AMP, ADP, GTP and a non-hydrolysable ATP analogue
      (adenosine 5'-[alpha, beta-methylene] triphosphate), did not stimulate [3H]UCB
      transport, indicating that ATP hydrolysis was necessary for the stimulatory
      effect. [3H]UCB uptake occurred into an osmotically sensitive space. At an
      unbound bilirubin concentration ([Bf]) below saturation of the aqueous phase (no
      more than 70 nM UCB), the ATP-dependent transport followed saturation kinetics
      with respect to [Bf], with a Km of 26+/-8 nM and a Vmax of 117+/-11 pmol per 15 s
      per mg of protein. Unlabelled UCB inhibited the uptake of [3H]UCB, indicating
      that UCB was the transported species. Inhibitors of ATPase activity such as
      vanadate or diethyl pyrocarbonate decreased the ATP effect (59+/-11% and 100%
      respectively). Daunomycin, a known substrate for multidrug resistance protein-1,
      and taurocholate did not inhibit the ATP-dependent [3H]UCB transport, suggesting
      that neither mdr-1 nor the canalicular bile acid transporter is involved in the
      canalicular transport of UCB. [3H]UCB uptake (both with and without ATP) in
      canalicular vesicles obtained from TR- rats was comparable to that in vesicles
      obtained from Wistar rats, indicating that the canalicular multispecific organic
      anion transporter, cMOAT, does not account for UCB transport. These results
      indicate that UCB is transported across the canalicular membrane of the liver
      cell by an ATP-dependent mechanism involving an as yet unidentified transporter.

PMID- 9512467
TI  - Induction of tissue transglutaminase by dexamethasone: its correlation to
      receptor number and transglutaminase-mediated cell death in a series of malignant
      hamster fibrosarcomas.
AB  - Treatment of the hamster fibrosarcoma cell lines (Met B, D and E) and BHK-21
      hamster fibroblast cells with the glucocorticoid dexamethasone led to a powerful
      dose-dependent mRNA-synthesis-dependent increase in transglutaminase activity,
      which can be correlated with dexamethasone-responsive receptor numbers in each
      cell line. Increasing the number of dexamethasone-responsive receptors by
      transfection of cells with the HG1 glucocorticoid receptor protein caused an
      increase in transglutaminase activity that was proportional to the level of
      transfected receptor. In all experiments the levels of the tissue
      transglutaminase-mediated detergent-insoluble bodies was found to be comparable
      with increases in transglutaminase activity. Despite an increase in detergent
      insoluble body formation, an increase in apoptosis as measured by DNA
      fragmentation was not found. Incubation of cells with the non-toxic competitive
      transglutaminase substrate fluorescein cadaverine led to the incorporation of
      this fluorescent amine into cellular proteins when cells were damaged after
      exposure to trypsin during cell passage. These cross-linked proteins containing
      fluorescein cadaverine were shown to be present in the detergent-insoluble
      bodies, indicating that the origin of these bodies is via activation of tissue
      transglutaminase after cell damage by trypsinization rather than apoptosis per
      se, since Met B cells expressing the bcl-2 cDNA were not protected from detergent
      insoluble body formation. We describe a novel mechanism of cell death related to
      tissue transglutaminase expression and cell damage.

PMID- 9512468
TI  - Proxy activation of protein ErbB2 by heterologous ligands implies a
      heterotetrameric mode of receptor tyrosine kinase interaction.
AB  - The oncoprotein ErbB2 is frequently overexpressed in human tumours, but no
      activating ErbB2-specific ligand has yet been identified. Here we analyse the
      catalytic and oligomeric behaviour of ErbB2 using phosphorylation-state-specific
      antibodies which distinguish kinase-active and -inactive ErbB2 receptor subsets.
      Heregulin-alpha (HRG) activates ErbB2 in G8/DHFR 3T3 cells by selectively
      inducing hetero-oligomerization with kinase-defective ErbB3, indicating that
      heterologous transphosphorylation is an unlikely prerequisite for ErbB2
      activation. HRG also triggers association of epidermal-growth-factor receptors
      (EGFR) with a kinase-inactive ErbB2 subset while reducing EGFR association with
      active ErbB2. Similarly, EGF treatment of A431 cells induces concomitant hetero
      oligomerization of active ErbB2 with inactive EGFR, of active EGFR with inactive
      ErbB2, and of inactive ErbB2 with kinase-defective ErbB3. These combinatorial
      patterns of ligand-dependent oligomerization suggest a multivalent model of
      receptor tyrosine kinase interaction in which liganded homodimers provide stable
      oligomerization interfaces for unliganded ErbB2 or other bystander receptors. We
      submit that ErbB2 may be physiologically activated via a 'proxy' ligand-inducible
      heterotetrameric mechanism similar to that already established for transforming
      growth-factor-beta type I receptors.

PMID- 9512469
TI  - Regulation of mitochondrial biogenesis in brown adipose tissue: nuclear
      respiratory factor-2/GA-binding protein is responsible for the transcriptional
      regulation of the gene for the mitochondrial ATP synthase beta subunit.
AB  - The regulation of transcription of the gene for the beta subunit of the FoF1 ATP
      synthase (ATPsynbeta) in brown adipose tissue has been studied as a model to
      determine the molecular mechanisms for mitochondrial biogenesis associated with
      brown adipocyte differentiation. The expression of the ATPsynbeta mRNA is induced
      during the brown adipocyte differentiation that occurs during murine prenatal
      development or when brown adipocytes differentiate in culture. This induction
      occurs in parallel with enhanced gene expression for other nuclear and
      mitochondrially-encoded components of the respiratory chain/oxidative
      phosphorylation system (OXPHOS). Transient transfection assays indicated that the
      expression of the ATPsynbeta gene promoter is higher in differentiated HIB-1B
      brown adipocytes than in non-differentiated HIB-1B cells. A major transcriptional
      regulatory site was identified between nt -306 and -266 in the ATPsynbeta
      promoter. This element has a higher enhancer capacity in differentiated brown
      adipocyte HIB-1B cells than in non-differentiated cells. Electrophoretic shift
      analysis indicated that Sp1and nuclear respiratory factor-2/GA-binding protein
      (NRF2/GABP) were the main nuclear proteins present in brown adipose tissue that
      bind this site. Double-point mutant analysis indicated a major role for the
      NRF2/GABP site in the enhancer capacity of this element in brown fat cells. It is
      proposed that NRF2/GABP plays a pivotal role in the co-ordinated enhancement of
      OXPHOS gene expression associated with mitochondrial biogenesis in brown
      adipocyte differentiation.

PMID- 9512470
TI  - Bombesin stimulates cholecystokinin secretion through mitogen-activated protein
      kinase-dependent and -independent mechanisms in the enteroendocrine STC-1 cell
      line.
AB  - Bombesin has been reported to stimulate cholecystokinin (CCK) secretion from rat
      duodeno-jejunal I-cells. Bombesin was shown to activate mitogen-activated protein
      kinases (MAPKs) in cell types such as Swiss 3T3 fibroblasts and rat pancreatic
      acinar cells. No information is available on whether MAPK is activated in
      intestinal endocrine cells upon bombesin stimulation. This was studied by using
      the CCK-producing enteroendocrine cell line STC-1. Bombesin stimulated markedly
      and transiently both p42(MAPK) and p44(MAPK), with a maximum at 2 min, and a
      decrease to basal levels within 10 min. As expected, bombesin stimulated MAPK
      kinase 1 (MEK-1) activity. Activation of protein kinase C (PKC) with PMA also
      stimulated p42(MAPK), p44(MAPK) and MEK-1. Treatment of cells with PD 098059 (at
      10 microM or 30 microM), which selectively inhibits MEK phosphorylation, blocked
      bombesin-induced p42(MAPK) and p44(MAPK) activation for at least 90 min. However,
      PD 098059 inhibited bombesin- and PMA-stimulated CCK secretion during the first
      15 min, but failed to significantly reduce CCK release at later times. Inhibition
      of PKC with staurosporine, or PKC down-regulation by prolonged treatment with
      PMA, both drastically decreased MEK-1, p42(MAPK) and p44(MAPK) activation upon
      bombesin stimulation. Additionally, PKC activation appeared to be required for
      both MAPK-dependent (early) and -independent (late) CCK responses to bombesin. It
      is concluded that the early CCK secretory response of STC-1 cells to bombesin
      involves MAPK pathway activation through a PKC-dependent mechanism, whereas the
      late phase of bombesin-induced CCK secretion, that also requires PKC, appears to
      result from a MAPK-independent process.

PMID- 9512471
TI  - Effector-sensitive cross-linking of phosphorylase b kinase by the novel cross
      linker 4-phenyl-1,2,4-triazoline-3,5-dione.
AB  - The dienophile 4-phenyl-1,2,4-triazoline-3,5-dione (PTD) was identified as a
      novel protein cross-linker, and utilized as a conformational probe of
      phosphorylase b kinase (PhK), a hexadecameric enzyme with the subunit composition
      (alphabetagammadelta)4. In its reaction with this enzyme, PTD produced five major
      cross-linked conjugates as resolved by denaturing gel electrophoresis: alphabeta,
      betagammagamma, alphagamma and a doublet of differently migrating homodimers,
      betabeta1 and betabeta2. Cross-linking in the presence of six different
      activators of the kinase targeted to its various subunits caused substantial
      changes in the amounts of three of the conjugates. The formation of alphagamma
      was increased by all of the activators but the largest enhancement was caused by
      exogenous Ca2+/calmodulin. All except one of the activators decreased the amount
      of betagammagamma formed, with Mg2+ having the greatest effect, and all except
      two increased the amount of betabeta1, with Mg2+ again having the largest
      influence. From the overall similarity of the changes in cross-linking by PTD
      induced by the various activators, we conclude that, even though they are
      targeted to different sites and subunits, they induce activated conformations of
      PhK that have certain structural features in common. Regarding the mechanism of
      cross-linking by PTD, its reaction with a model nucleophile suggests that its
      initial reaction with a side chain nucleophile of PhK involves a 1,4-conjugate
      addition to form a urazole adduct, with the secondary cross-linking reaction
      occurring through an as yet unknown pathway.

PMID- 9512472
TI  - Effect of replacement of His-118, His-125 and Trp-143 by alanine on the catalytic
      activity and subunit assembly of inorganic pyrophosphatase from thermophilic
      bacterium PS-3.
AB  - Each of two histidine residues and one tryptophan residue in thermophilic
      bacterium PS-3 inorganic pyrophosphatase (PPase) was replaced by alanine. The
      activities of the H125A and W143A variants decreased to one-fifth, whereas the
      activity of H118A remained unaltered. CD spectra in the near-UV region indicated
      that the conformations of the first two variants changed with the substitution.
      In contrast with wild-type PPase, which is hexameric beyond an enzyme
      concentration of 0.1 microM in the presence of Mg2+, the H118A and H125A variants
      cannot be assembled from trimers into hexamers at less than an enzyme
      concentration of 10 microM even at a higher concentration of Mg2+. In particular,
      H118A was irreversibly inactivated in a diluted state. In contrast, the enzyme
      concentration dependence of W143A PPase activity was almost the same as that of
      wild-type PPase. These results indicated that His-118 and His-125 are important
      for both trimer-trimer interaction and structural integrity, whereas Trp-143 is
      important structurally. The trimer-trimer interaction is absolutely necessary for
      the thermostability of the PS-3 enzyme.

PMID- 9512473
TI  - Activation of calcineurin and smooth muscle myosin light chain kinase by Met-to
      Leu mutants of calmodulin.
AB  - The effects of replacement of each of the individual Met in calmodulin (CaM) with
      Leu on the activation of two CaM target enzymes [smooth muscle myosin light chain
      kinase (smMLCK) and calcineurin (CN)] were investigated. The KD and Pmax
      (percentage maximal activation) values for activation of both enzymes by M76L-CaM
      were indistinguishable from wild-type (wt)-CaM, which is consistent with the
      location of Met-76 in the central linker that is not involved in target protein
      interaction. The other eight Met in CaM are exposed in the hydrophobic surfaces
      that are involved in target-enzymes binding, and in general equivalent effects
      are observed for substitutions of Leu for Met residues in homologous positions in
      the two CaM domains. However, the importance of the interaction of specific Met
      residues with the target enzyme depends on the particular enzyme. Leu
      substitution at Met-36 or Met-109 reduced the affinity of MLCK for the mutant and
      the maximal activation of CN. MLCK had a higher KD for M51L-CaM whereas M124L-CaM
      activated the kinase to only 68% of maximal activity induced by wt-CaM; these
      mutants were indistinguishable from wt-CaM in activation of CN. M71L- and M144L
      CaMs behaved like wt-CaM in activation of MLCK, but activated the phosphatase to
      only about 80% of maximal activity induced by wt-CAM. M72L-CaM exhibited an
      increased affinity for MLCK compared to wt-CaM and slightly decreased maximal
      activation, whereas M145L-CaM exhibited maximal activation significantly greater
      than that due to wt-CaM; these mutants behaved like wt-CaM with respect to CN
      activation. Finally, a mutant CaM in which all four C-terminal Met were replaced
      by Leu (M4-CT-L4-CaM) had similar affinities for MLCK and CN as wt-CaM but
      maximal activation of these enzymes by this mutant was only 60-70% of that
      achieved with wt-CaM. These results imply that, in addition to removing the
      autoinhibitory domain from the active site of the target enzyme, CaM must induce
      a conformational change in the active site itself.

PMID- 9512474
TI  - Effects of dietary treatment of rats with eicosapentaenoic acid or
      docosahexaenoic acid on hepatic lipid metabolism.
AB  - (1) Effects of dietary treatment of male albino rats with eicosapentaenoic acid
      (EPA) or docosahexaenoic acid on hepatic mitochondrial lipid metabolism have been
      investigated. (2) Mitochondria isolated from rats given these treatments were
      shown to have increased ability to respire on acyl-CoA esters in the presence of
      malonate. This effect was expressed with most of the long-chain acyl-CoA esters
      used as substrates. When malonate in the incubations was replaced with malate,
      mitochondria from treated animals were found to exhibit diminished rates of
      respiration on polyunsaturated acyl-CoA esters, in particular linolenoyl-,
      eicosapentaenoyl- and docosahexaenoyl-CoA. This phenomenon could not be
      attributed to changes in activity of carnitine palmitoyltransferase I or in
      peroxisomal beta-oxidation. (3) Uncoupled respiration on glutamate, malate or
      succinate was also affected by treatment with EPA. With liver mitochondria
      isolated from rats that had been treated with a omega-3 fatty acid in the fasted
      state, the respiratory rates were lower than those observed with mitochondria
      isolated from control rats. Respiratory rates with mitochondria isolated from
      rats given the omega-3 fatty acid in the fed state was not significantly
      different from control rates. (4) In rats treated with EPA in the fed state, the
      amount of EPA incorporated into mitochondrial lipids was markedly more increased
      as compared to rats given omega-3 fatty acid in the fasted state. Incorporation
      of dietary EPA into tissue lipids was investigated, also following mildronate
      treatment of rats (an inhibitor of carnitine biosynthesis). (5) A hypolipidaemic
      effect of dietary EPA was only observed when the fatty acid was given to fed
      rats. Rats treated with EPA in the fasted state, in contrast, exhibited
      hypoglycaemia, the hypolipidaemic effects now being absent. (6) These results
      suggest that hypolipidaemia is most pronounced when the metabolic state favours
      incorporation of dietary EPA into body lipids rather than its beta-oxidation, as
      mediated by the fed/fasted transition or by treatment with mildronate.

PMID- 9512475
TI  - Membrane integration of Sec61alpha: a core component of the endoplasmic reticulum
      translocation complex.
AB  - The Sec61 complex is a central component of the endoplasmic reticulum (ER)
      translocation site. The complex consists of three subunits: Sec61alpha, Sec61beta
      and Sec61gamma, at least two of which (alpha and beta) are adjacent to nascent
      proteins during membrane insertion. Another component of the translocation
      machinery is the translocating chain-associating membrane (TRAM) protein, which
      is also adjacent to many nascent proteins during membrane insertion. Sec61alpha
      functions as the major component of a transmembrane channel formed by oligomers
      of the Sec61 complex. This channel is the site of secretory protein translocation
      and membrane protein integration at the ER membrane. Sec61alpha is a polytopic
      integral membrane protein, and we have studied its biosynthesis and membrane
      integration in vitro. Using a cross-linking approach to analyse the environment
      of a series of discrete Sec61alpha membrane-integration intermediates, we find:
      (i) newly synthesized Sec61alpha is adjacent to known components of the ER
      membrane-insertion site, namely Sec61alpha, Sec61beta and TRAM, and thus the
      integration of Sec61alpha appears to require a pre-existing Sec61 complex; (ii) a
      site-specific cross-linking analysis indicates that the first transmembrane
      domain of Sec61alpha remains adjacent to protein components of the ER-insertion
      site (specifically TRAM and Sec61beta) during the insertion of at least three
      subsequent transmembrane domains; and (iii) the membrane integration of
      Sec61alpha requires ER targeting by the signal-recognition particle.

PMID- 9512476
TI  - Determination of functional domains in polypyrimidine-tract-binding protein.
AB  - Polypyrimidine-tract-binding protein (PTB) is involved in pre-mRNA splicing and
      internal-ribosomal-entry-site-dependent translation. The biochemical properties
      of various segments of PTB were analysed in order to understand the molecular
      basis of the PTB functions. The protein exists in oligomeric as well as monomeric
      form. The central part of PTB (amino acids 169-293) plays a major role in the
      oligomerization. PTB contains several RNA-binding motifs. Among them, the C
      terminal part of PTB (amino acids 329-530) exhibited the strongest RNA-binding
      activity. The N-terminal part of PTB is responsible for the enhancement of RNA
      binding by HeLa cell cytoplasmic factor(s).

PMID- 9512477
TI  - 125I-Labelled mapacalcine: a specific tool for a pharmacological approach to a
      receptor associated with a new calcium channel on mouse intestinal membranes.
AB  - Mapacalcine is a small protein (Mr=19041) composed of two homologous chains
      purified from the marine sponge Cliona vastifica. Recently, we demonstrated that
      it was able to specifically block a Ca2+ channel which could not be related to
      already described channels on mouse intestinal myocytes. This Ca2+ current was
      insensitive to the known peptidic and organic calcium channel blockers.
      Mapacalcine was ineffective on T-type and L-type Ca2+ currents present on rat
      portal vein myocytes [Morel, Drobecq, Sautiere, Tartar, Mironneau, Qar, Lavie,
      and Hugues (1997) Mol. Pharmacol. 51, 1042-1052]. We report here the preparation
      and purification of a monoiodo-derivative of mapa-calcine which retains its
      biological properties. Binding parameters of mapacalcine to its receptors have
      been characterized on mouse intestinal membranes. It binds to its receptors with
      a Kd=0. 8 nM, and a maximal binding capacity of 171 fmol/mg of protein on
      membrane preparations. Our data show that we have prepared a tool that is usable
      for pharmacological studies of a receptor associated with a new type of calcium
      channel for which no ligand was available until now.

PMID- 9512478
TI  - Oxidation of high-density lipoprotein HDL3 leads to exposure of apo-AI and apo
      AII epitopes and to formation of aldehyde protein adducts, and influences binding
      of oxidized low-density lipoprotein to type I and type III collagen in vitro1.
AB  - The changes in the immunological properties of apolipoprotein AI (apo-AI) and AII
      (apo-AII) during the oxidation of the high-density lipoprotein HDL3 and its
      influence on the binding of heavily oxidized low-density lipoprotein (LDL) to
      type I and III collagen were investigated. Oxidation of HDL3 or Eu3+-labelled
      HDL3 was performed with CuSO4, varying the time of oxidation. Oxidation of HDL3
      resulted in an increase in lipid hydroperoxides and enhanced the negative charge
      of this lipoprotein. Immunological studies with a solid-phase sandwich
      immunoassay revealed a strong increase in binding of Eu3+-labelled HDL3 to
      polyclonal antibodies against apo-AI and apo-AII within the first 4 h of
      oxidation. Neo-epitopes were also formed by interaction of the apolipoproteins
      with degradation products from the lipid peroxidation of polyunsaturated fatty
      acids, as evidenced by an immunoreaction of oxidized Eu3+-labelled HDL3 with
      antibodies to 4-hydroxynonenal (4-HNE)- and malondialdehyde (MDA)-protein
      adducts. Western blot analysis of oxidized HDL3 samples showed, as well as apo-AI
      and apo-AII bands, larger aggregated apolipoproteins, occurring after 0.5-2.5 h
      of oxidation. These aggregates were recognized by antibodies to apo-AI and apo
      AII as well as by antibodies to 4-HNE- and MDA-protein adducts. Furthermore the
      original apo-AI monomers and apo-AII dimers decreased during the oxidation. The
      ability of native and oxidized HDL3 to prevent the binding of Eu3+-labelled 24 h
      oxidized LDL to collagen on microtitration plates was estimated. Interestingly, 2
      h-oxidized HDL3 competed most with the binding of 24 h-oxidized LDL on collagen
      type I and type III, followed by native HDL3. However, 24 h-oxidized HDL3 was a
      weaker competitor. Thus oxidative modification of HDL3 strongly alters the
      immunological properties of this lipoprotein and its binding affinity for
      collagen.

PMID- 9512479
TI  - Bovine submaxillary mucin contains multiple domains and tandemly repeated non
      identical sequences.
AB  - A number of cDNA fragments coding for bovine submaxillary mucin (BSM) were
      cloned, and the nucleotide sequence of the largest clone, BSM421, was determined.
      Two peptide sequences determined from the purified apoBSM were found near the N
      terminus of the mucin-coding region of BSM421. This clone does not contain a
      start or stop codon, but its 3' end overlaps with the 5' end of a previously
      isolated clone, lambdaBSM10. The composite sequence of 1589 amino acid residues
      consists of five distinct protein domains, which are numbered from the C
      terminus. The cysteine-rich domain I can be further divided into a von Willebrand
      factor type C repeat and a cystine knot. Domains III and V consist of similar
      repeated peptide sequences with an average of 47 residues. Domains II and IV do
      not contain such sequences but are similar to domains III and V in being rich in
      serine and threonine, many of which are predicted to be potential O-glycosylation
      sites. Domain III also contains two sequences that match the ATP/GTP-binding site
      motif A (P-loop). Only beta-strands and no alpha-helices are predicted for the
      partial deduced amino acid sequence. Northern analysis of submaxillary gland RNA
      with the BSM421 probe detected multiple messages of BSM with sizes from 1.1 to
      over 10 kb. The tandemly repeated, non-identical peptide sequences of approx. 47
      residues in domains III and V of BSM differ from the tandemly repeated, identical
      81-residue sequences of pig submaxillary mucin (PSM), although both BSM and PSM
      contain similar C-terminal domains. In contrast, two peptide sequences of ovine
      submaxillary mucin are highly similar (86% and 65% identical respectively) to the
      corresponding sequences in domain V of BSM.

PMID- 9512480
TI  - Purification and characterization of high- and low-molecular-mass isoforms of
      phosphoenolpyruvate carboxylase from Chlamydomonas reinhardtii. Kinetic,
      structural and immunological evidence that the green algal enzyme is distinct
      from the prokaryotic and higher plant enzymes.
AB  - Phosphoenolpyruvate carboxylase (PEPC) is a key enzyme in the supply of carbon
      skeletons for the assimilation of nitrogen by green algae. Two PEPC isoforms with
      respective native molecular masses of 400 (PEPC1) and 650 (PEPC2) kDa have been
      purified from Chlamydomonas reinhardtii CW-15 cc1883 (Chlorophyceae). SDS/PAGE,
      immunoblot and CNBr peptide-mapping analyses indicate the presence of the same
      100 kDa PEPC catalytic subunit in both isoforms. PEPC1 is a homotetramer, whereas
      PEPC2 seems to be a complex between the PEPC catalytic subunit and other
      immunologically unrelated polypeptides of 50-70 kDa. Kinetic analyses indicate
      that these PEPC isoforms are (1) differentially regulated by pH, (2) activated by
      glutamine and dihydroxyacetone phosphate and (3) inhibited by glutamate,
      aspartate, 2-oxoglutarate and malate. These results are consistent with the
      current model for the regulation of anaplerotic carbon fixation in green algae,
      and demonstrate that green algal PEPCs are uniquely regulated by glutamine.
      Several techniques were used to assess the structural relationships between C.
      reinhardtii PEPC and the higher plant or prokaryotic enzyme. Immunoblot studies
      using anti-(green algal or higher plant PEPC) IgGs suggested that green algal (C.
      reinhardtii, Selenastrum minutum), higher plant (maize, banana fruit, tobacco)
      and prokaryotic (Synechococcus leopoliensis, Escherichia coli) PEPCs have little
      or no immunological relatedness. Moreover, the N-terminal amino acid sequence of
      the C. reinhardtii PEPC subunit did not have significant similarity to the highly
      conserved corresponding region in enzymes from higher plants, and CNBr cleavage
      patterns of green algal PEPCs were distinct from those of higher plant and
      cyanobacterial PEPCs. These results point to significant evolutionary divergence
      between green algal, higher plant and prokaryotic PEPCs.

PMID- 9512481
TI  - Binding of alpha-melanocyte-stimulating hormone to its G-protein-coupled receptor
      on B-lymphocytes activates the Jak/STAT pathway.
AB  - alpha-Melanocyte-stimulating hormone (alpha-MSH) is a 13-amino-acid peptide with
      a variety of physiological effects, including the stimulation of melanocyte
      proliferation and melanogenesis, temperature control, control of prolactin
      release and the modulation of cytokine action in the immune system. There are
      five known subtypes of G-protein-coupled receptors, which bind with different
      affinities to alpha-MSH. This paper provides evidence that Ba/F3 pro-B-lymphocyte
      cells express the gene for the melanocortin 5 (MC5) receptor and specifically
      bind alpha-MSH. Western-blot analysis reveals that alpha-MSH binding stimulates
      Janus kinase 2 (JAK2) and signal transducers and activators of transcription
      (STAT1) tyrosine phosphorylation in both Ba/F3 cells and human cultured IM-9
      lymphocytes. alpha-MSH is further revealed to activate JAK2 in mouse L-cells
      stably expressing the human MC5 receptor. Finally, alpha-MSH binding is shown to
      result in an enhancement of cellular proliferation. These findings identify a new
      protein tyrosine kinase pathway in the action of alpha-MSH, and suggest that
      alpha-MSH plays an important role in B-lymphocyte function via the activation of
      the same intracellular phosphorylation pathway used by cytokines and growth
      factors.

PMID- 9512482
TI  - A mitochondrial membrane protein is required for translocation of
      phosphatidylserine from mitochondria-associated membranes to mitochondria.
AB  - The mechanism of import of phosphatidylserine (PtdSer) into mitochondria was
      investigated using a reconstituted system of isolated organelles in vitro in
      which PtdSer was translocated from donor membranes to mitochondria and was
      decarboxylated therein. Neither phosphatidylcholine nor phosphatidylethanolamine
      (PtdEtn) was translocated under the same conditions. Transfer of PtdSer from its
      site of synthesis on the endoplasmic reticulum and mitochondria-associated
      membranes [J. E.Vance (1990) J. Biol. Chem. 265, 7248-7256] to its site of
      decarboxylation on mitochondrial inner membranes is predicted to be mediated by
      membrane contact. A mitochondrial membrane protein appears to be involved in the
      translocation event since proteolysis of proteins exposed on the mitochondrial
      surface potently inhibited PtdSer transfer, whereas proteolysis of surface
      proteins of mitochondria-associated membranes did not impair the transfer. The
      nature of the membranes that donate PtdSer to mitochondria in vitro is not
      crucial since PtdSer of mitochondria-associated membranes, endoplasmic reticulum
      and microsomes was decarboxylated to PtdEtn with approximately equal efficiency.
      The translocation of PtdSer to mitochondria was stimulated by magnesium and
      calcium ions and was inhibited by incubation of mitochondria with sulphydryl
      group-modifying reagents. Reconstitution of PtdSer translocation/decarboxylation
      using digitonin-solubilized mitochondria and PtdSer-donor membranes suggested
      that the putative PtdSer-translocation protein is primarily localized to contract
      sites between mitochondrial inner and outer membranes. These studies provide
      evidence for the involvement of a mitochondrial membrane protein in the import of
      newly-synthesized PtdSer into mitochondria.

PMID- 9512483
TI  - Dietary carbohydrates enhance lactase/phlorizin hydrolase gene expression at a
      transcription level in rat jejunum.
AB  - We have previously shown that dietary sucrose stimulates the lactase/phlorizin
      hydrolase (LPH) mRNA accumulation along with a rise in lactase activity in rat
      jejunum [Goda, Yasutake, Suzuki, Takase and Koldovsky (1995) Am. J. Physiol. 268,
      G1066-G1073]. To elucidate the mechanisms whereby dietary carbohydrates enhance
      the LPH mRNA expression, 7-week-old rats that had been fed a low-carbohydrate
      diet (5.5% of energy as starch) were given diets containing various
      monosaccharides or sucrose for 12h. Among carbohydrates examined, fructose,
      sucrose, galactose and glycerol elicited an increase in LPH mRNA accumulation
      along with a rise in lactase activity in the jejunum. By contrast, glucose and
      alpha-methylglucoside were unable to elicit a significant increase in LPH mRNA
      levels. To explore a transcriptional mechanism for the carbohydrate-induced
      increases in LPH mRNA levels, we employed two techniques currently available to
      estimate transcriptional rate, i.e. RNA protection assays of pre-mRNA using an
      intron probe, and nuclear run-on assays. Both assays revealed that fructose
      elicited an increase in transcription of the LPH gene, and that the transcription
      of LPH was influenced only slightly, if at all, by glucose intake. These results
      suggest that certain monosaccharides such as fructose or their metabolite(s) are
      capable of enhancing LPH mRNA levels in the small intestine, and that
      transcriptional control might play a major role in the carbohydrate-induced
      increase of LPH mRNA expression.

PMID- 9512484
TI  - Apolipoprotein J (clusterin) induces cholesterol export from macrophage-foam
      cells: a potential anti-atherogenic function?
AB  - Apolipoprotein J (apo J) is a secreted glycoprotein of which the exact function
      remains a matter for speculation. Apo J has been implicated in such diverse
      processes as sperm maturation, regulation of complement activation, programmed
      cell death, tissue remodelling and lipid transport. In this study a possible role
      for apo J in lipid transport was explored. Mouse peritoneal macrophages were
      incubated with acetylated low-density lipoprotein (AcLDL) to produce foam cells
      containing cholesterol and cholesteryl esters. Incubation of the foam cells with
      physiological concentrations of purified apo J led to a dose-dependent export of
      cholesterol. The appearance of cholesterol in the medium was associated
      predominantly with a decline in intracellular cholesteryl esters rather than
      intracellular free cholesterol. The kinetics of cholesterol release to apo J were
      similar to apo A-I, an established promoter of cholesterol efflux. Apo J was also
      shown to induce phospholipid efflux from cells, whereas the cholesterol exported
      to the medium was associated with the apo J. Studies using foam cells from apo E
      null mice showed that the cholesterol exported to the medium was independent of
      apo E production by the cells. These results present the first evidence that apo
      J can promote cholesterol efflux from foam cells and indicates that it might have
      a function in cellular cholesterol homoeostasis in both normal and pathological
      situations.

PMID- 9512485
TI  - Purification and characterization of a new cystatin inhibitor from Taiwan cobra
      (Naja naja atra) venom.
AB  - Cobra cystatin, a new cysteine-proteinase inhibitor of the cystatin superfamily,
      was isolated from the venom of the Taiwan cobra (Naja naja atra) by affinity
      chromatography on S-carboxymethylpapain-Sepharose and reverse-phase
      chromatography. The venom contained two forms of the inhibitor, one of 11870 Da
      and the other of 12095 Da, as determined by MS, and pI values of 6.2 and 6.1.
      Cobra cystatin strongly inhibits cysteine proteinases of the papain family, but
      not calpain. Papain, cathepsin L, cathepsin B and cathepsin S are inhibited with
      Ki values of 0.19, 0.1, 2.5 and 1.2 nM respectively. The amino acid sequence of
      cobra cystatin shows that it is a Type 2 cystatin. The amino acid sequence is 73%
      identical with that of the cystatin in African-puff-adder (Bitis arietans) venom,
      with which it shares a unique six-residue insertion in a region opposite the
      reactive inhibitory site. Cobra cystatin is 25-42% identical with other Type 2
      cystatins, the most closely related being the recently described human cystatin
      M, which also has a similar five-residue insertion starting at position 76
      (chicken cystatin numbering). A molecular phylogenetic tree of 16 representative
      members of Family 2 cystatins was constructed by parsimony analysis; it suggests
      that snake cystatins, together with Tachypleus tridentatus (Japanese horseshoe
      crab) cystatin and human cystatin M, form a new subfamily within cystatin Family
      2.

PMID- 9512486
TI  - Anti-phospholamban and protein kinase A alter the Ca2+ sensitivity and maximum
      velocity of Ca2+ uptake by the cardiac sarcoplasmic reticulum.
AB  - The activity of the SERCA2a Ca2+ pump in the sarcoplasmic reticulum (SR) of
      cardiac muscle is inhibited by phospholamban. When phospholamban is
      phosphorylated by cyclic-AMP-dependent protein kinase (PKA) this inhibition is
      relieved. It is generally agreed that this results in an increase in the Ca2+
      sensitivity of the SR Ca2+ pump; however, some investigators have also reported
      an increase in the maximum velocity of the pump. We have used a sensitive
      fluorescence method to measure net Ca2+ uptake by native cardiac SR vesicles and
      compared the effects of a constitutively active subunit of PKA (cPKA) with those
      of a monoclonal antibody (A1) that binds to phospholamban and is thought to mimic
      the effect of phosphorylation. Both the Ca2+ sensitivity and the maximum velocity
      of uptake were increased by cPKA and by A1. The effects of cPKA and A1 on uptake
      velocity were only slightly additive. No changes in uptake were detected with
      denatured cPKA or denatured A1. These results indicate that the functional effect
      of phospholamban phosphorylation is to increase both the Ca2+ sensitivity and the
      maximum velocity of net Ca2+ uptake into the SR.

PMID- 9512487
TI  - Utilization of phosphatidylcholine and production of diradylglycerol as a
      consequence of sphingomyelin synthesis.
AB  - 1. After the degradation of cell-surface sphingomyelin (SM) by exogenous
      sphingomyelinase (SMase), the resynthesis of SM by baby-hamster kidney (BHK) and
      human leukaemia-60 (HL-60) cells was examined in relation to utilization of
      substrate phosphatidylcholine (PtdCho) and generation of the expected product,
      diradylglycerol (DRG). Using [3H]choline-labelled BHK cells incubated in non
      radioactive medium, SMase caused a release of phosphocholine, which was derived
      approximately equally from SM and PtdCho, consistent with the anticipated
      resynthesis of SM at the expense of PtdCho. However, with choline-labelled cells
      incubated in radioactive medium or [14C]acetate-labelled cells treated with
      SMase, no loss of radioactivity from PtdCho or accumulation of labelled DRG was
      observed, suggesting that any DRG produced as a consequence of SM synthesis must
      have been rapidly converted back into PtdCho. In contrast, SMase treatment of HL
      60 cells caused more than a doubling of DRG levels at the expense of PtdCho, and
      this appears to be the first demonstration of a rise in DRG related to the
      synthesis of SM. The DRG produced consisted of about 80% 1,2-diacylglycerol and
      18% 1-O-alkyl-2-acylglycerol species, a similar composition to that of the DRG
      backbone of total cell PtdCho. 2. The requirement for cell-surface PtdCho in the
      biosynthesis of SM by BHK cells was also investigated. Treatment of [3H]choline
      labelled BHK cells with Bacillus cereus PtdCho-specific phospholipase C (PLC)
      rapidly degraded about 6% of the total PtdCho, which was assumed to represent the
      cell-surface pool. This did not appear to be the pool of PtdCho required for SM
      synthesis, since (a) the released phosphocholine was additional to that derived
      from PtdCho in cells treated with SMase and (b) treatment with PLC did not affect
      SM synthesis, either de novo or in response to degradation of cell-surface SM by
      SMase. These findings suggest either that there is no SM synthase in the plasma
      membrane or, if it is present, then it does not utilize cell-surface PtdCho as a
      substrate.

PMID- 9512488
TI  - Mutational analysis of histidine residues in the rabbit Na+/dicarboxylate co
      transporter NaDC-1.
AB  - Succinate transport by the rabbit Na+/dicarboxylate co-transporter, NaDC-1,
      expressed in Xenopus oocytes was inhibited by the histidyl-selective reagent
      diethyl pyrocarbonate (DEPC). Therefore the role of histidine residues in the
      function of NaDC-1 was examined by site-directed mutagenesis. All 11 histidine
      residues in NaDC-1 were converted to alanine, but only mutant H106A exhibited a
      decrease in succinate transport. Additional mutations of NaDC-1 at position 106
      showed that aspartic acid and asparagine, but not arginine, can substitute for
      histidine. Examination of succinate and citrate kinetics of H106A revealed a
      decrease in Vmax with no change in Km. Cell surface biotinylation experiments
      showed that the transport activity of all four mutants at position 106 was
      correlated with the amount of cell surface expression, suggesting a role of His
      106 in membrane expression rather than function. Two of the histidine mutants,
      H153A and H569A, exhibited insensitivity to inhibition by DEPC, indicating that
      these residues are involved in binding DEPC. Neither of these residues is
      required for transport activity; thus DEPC probably inhibits NaDC-1 function by
      hindrance of the mobility of the carrier. We conclude that histidine residues are
      not critical for transport function in NaDC-1, although His-106 might be involved
      in determining protein expression or stability in the membrane.

PMID- 9512489
TI  - Characterization of a spleen sulphotransferase responsible for the 6-O-sulphation
      of the galactose residue in sialyl-N-acetyl-lactosamine sequences.
AB  - An enzyme which catalyses the transfer of sulphate from 3'-phosphoadenosine 5'
      phosphosulphate (PAPS) to C-6 of galactose in the NeuAcalpha2-3Galbeta1-4GlcNAc
      (3'SLN) sequence has been found in rat spleen microsomes and its specificity
      indicates that it is well suited to participate in the assembly of 3'-sialyl-6'
      sulpho-LacNAc [NeuAcalpha2-3Gal(6-SO4)beta1-4GlcNAc] and 3'-sialyl-6'-sulpho
      LewisX [NeuAcalpha2-3Gal(6-SO4)beta1-4(Fucalpha1-3)GlcNAc] saccharide groups
      which have been implicated as selectin ligands. This sulphotransferase has a
      strict requirement for oligosaccharide acceptors which are capped by an alpha2-3
      linked sialic acid residue, although GlcNAc in 3'SLN can be substituted by Glc,
      and Galbeta1-4GlcNAc can be replaced by Galbeta1-3GlcNAc without loss of
      activity. The finding that 3'-sialyl LewisX was inert as an acceptor suggested
      that fucosylation, in contrast with sialylation, follows the addition of the
      sulphate group. Since fetuin glycopeptides containing the NeuAcalpha2-3Galbeta1
      4GlcNAc sequence had a similar affinity for the enzyme as the unattached 3'SLN,
      it would appear that the acceptor determinants reside primarily in the peripheral
      trisaccharide constellation. The position of the sulphate on C-6 of galactose was
      elucidated by Smith periodate oxidation, hydrazine/nitrous acid/NaBH4 treatment
      and elder (Sambucus nigra) bark lectin chromatography of the desialylated
      [35S]sulphate-labelled products of the enzyme. Assays carried out with 3'SLN as
      acceptor indicated that the sulphotransferase had a pH optimum between 6.5 and
      7.0 and a dependence on a bivalent cation best met by Mn2+ (12-25 mM); Triton X
      100 (0.02 to 0.35%) brought about maximal stimulation. Tentative Km values
      determined for this enzyme were 4.7 microM for PAPS, and 0.72 mM and 1.16 mM for
      3'SLN and fetuin glycopeptides respectively. A survey of several rat organs
      indicated that the PAPS:3'SLN-6-O-sulphotransferase is selectively distributed
      with maximal activity occurring in spleen which was substantially greater than
      thymus or lymph nodes. In contrast, other enzymes (i.e. PAPS:Gal-3-O-and GlcNAc-6
      O-sulphotransferases) involved in the sulphation of sialyl-lactosamine and
      lactosamine sequences, which in the sulphated form are believed to also be
      selectin ligands, were more evenly distributed in lymphoid tissues. Relatively
      high activities for all three enzymes were found in brain.

PMID- 9512490
TI  - Disruption of endogenous regulator homeostasis underlies the mechanism of rat
      CYP1A1 mRNA induction by metyrapone.
AB  - The transcriptional induction of the cytochrome P-450 1A1 (CYP1A1) gene by
      xenobiotics such as polyaromatic hydrocarbons is dependent on their interaction
      with the aryl hydrocarbon receptor. Administration of the structurally unrelated
      compounds metyrapone (a cytochrome P-450 inhibitor) or dexamethasone (a
      glucocorticoid) to male rats does not induce hepatic CYP1A1 mRNA. However,
      administration of both metyrapone and dexamethasone to male rats results in the
      induction of hepatic CYP1A1 mRNA expression. The induction response is mimicked
      in vitro in cultured rat hepatocytes by the addition of metyrapone and
      dexamethasone to a serum-free culture medium, suggesting that these compounds act
      directly on the liver in vivo to effect hepatic CYP1A1 mRNA induction. An
      examination of the characteristics of CYP1A1 induction by metyrapone and
      dexamethasone in combination in vitro indicate that at least 6 h of treatment is
      required for detectable levels of CYP1A1 mRNA to accumulate in hepatocytes. In
      contrast, beta-naphthoflavone, which is known to bind to the aryl hydrocarbon
      receptor to effect CYP1A1 gene expression, induces detectable levels of CYP1A1
      mRNA within 2 h of treatment. CYP1A1 mRNA is also induced when hepatocytes are
      treated with metyrapone in combination with the protein synthesis inhibitor
      cycloheximide but not with dexamethasone in combination with cycloheximide,
      indicating that CYP1A1 mRNA induction is strictly dependent on the presence of
      metyrapone and suggesting that the metyrapone-associated induction of CYP1A1 mRNA
      is dependent on a loss of a constitutively expressed protein that functions to
      suppress CYP1A1 gene expression. The role of dexamethasone in metyrapone
      associated induction of CYP1A1 is probably mediated through the glucocorticoid
      receptor since the glucocorticoid receptor antagonist RU486 reduces the levels of
      CYP1A1 mRNA induced by metyrapone and dexamethasone in combination. Increasing
      the levels of the photosensitizer riboflavin present in the culture medium 10
      fold and exposure to light increases the levels of CYP1A1 mRNA induced by
      metyrapone and dexamethasone in combination in vitro, suggesting that
      photoactivation of inducing medium constituent(s) might be required for
      induction. Failure to induce CYP1A1 mRNA by co-administration of metyrapone and
      dexamethasone in hepatocytes cultured in a balanced salt solution with or without
      photoactivation indicates that induction is dependent on a photoactivated
      component of the culture medium and not on metyrapone or dexamethasone alone. The
      addition of tryptophan in the presence of riboflavin to the balanced salt
      solution restores CYP1A1 mRNA induction by metyrapone alone and induction is
      increased when medium is exposed to light, indicating that induction is dependent
      on tryptophan photoactivation in vitro. Metyrapone failed to compete with 2,3,7,8
      tetrachlorodibenzo-p-dioxin for specific binding to the aryl hydrocarbon receptor
      in rat liver cytosolic fractions. These results suggest that CYP1A1 might be
      induced in rats by metyrapone through an indirect mechanism associated with an
      elevation in the level of an endogenously generated inducer such as
      photoactivated product(s) of tryptophan and not because of metyrapone's
      interacting with the aryl hydrocarbon receptor. The dependence of CYP1A1
      induction on dexamethasone or cycloheximide suggests that derepression by a
      glucocorticoid receptor-modulated negative-acting factor of CYP1A1 gene
      expression might be critical to induction by metyrapone.

PMID- 9512491
TI  - Phospholipase C-delta1 and oxytocin receptor signalling: evidence of its role as
      an effector.
AB  - Although the oxytocin receptor modulates intracellular Ca2+ ion levels in
      myometrium, the identities of signal molecules have not been clearly clarified.
      Our previous studies on oxytocin receptor signalling demonstrated that 80 kDa
      Ghalpha is a signal mediator [Baek, Kwon, Lee, Kim, Muralidhar and Im (1996)
      Biochem. J. 315, 739-744]. To elucidate the effector in the oxytocin receptor
      signalling pathway, we evaluated the oxytocin-mediated activation of
      phospholipase C (PLC) by using solubilized membranes from human myometrium and a
      three-component preparation containing the oxytocin receptor-Ghalpha-PLC-delta1
      complex. PLC-delta1 activity in the three-component preparation, as well as PLC
      activity in solubilized membranes, was increased by oxytocin in the presence of
      Ca2+ and activated Ghalpha (GTP-bound Ghalpha). Furthermore the stimulated PLC
      delta1 activity resulting from activation of Ghalpha via the oxytocin receptor
      was significantly attenuated by the selective oxytocin antagonist desGly
      NH2d(CH2)5[Tyr(Me)2,Thr4]ornithine vasotocin or GDP. Consistent with these
      observations, co-immunoprecipitation and co-immunoadsorption of PLC-delta1 in the
      three-component preparation by anti-Gh7alpha antibody resulted in the PLC-delta1
      being tightly coupled to activated Ghalpha on stimulation of the oxytocin
      receptor. These results indicate that PLC-delta1 is the effector for Ghalpha
      mediated oxytocin receptor signalling.

PMID- 9512492
TI  - The two activation domains of the CCAAT-binding factor CBF interact with the
      dTAFII110 component of the Drosophila TFIID complex.
AB  - The CCAAT-binding factor CBF is a heterotrimeric transcription factor that
      specifically binds to CCAAT sequences in many eukaryotic genes. Previous studies
      have shown that CBF contains two transcription activation domains: a glutamine
      rich, serine-threonine-rich domain present in the CBF-B subunit and a glutamine
      rich domain in the CBF-C subunit. In this study, by using a series of deletion
      mutations of CBF-B and CBF-C in transcription assay in vitro, we further
      delineated smaller segments in these domains that were sufficient to support
      transcriptional activation by CBF. To test whether transcription activation by
      CBF requires co-activators, we examined the interaction between CBF and dTAF110,
      a component of the Drosophila TFIID complex. Recent work has demonstrated that
      glutamine-rich domains of the Sp1 transcription factor interact with dTAF110 and
      that this interaction has an important role in mediating transcription
      activation. Here we first demonstrate in a direct interaction assay in vitro that
      CBF binds dTAF110. By using a yeast two-hybrid system we show that both of the
      transcription activation domains of CBF interact with dTAF110. A deletion
      analysis suggests that a segment of CBF-B needed for transcription activation is
      also involved in interaction with dTAF110. In CBF-C the C-terminal portion of the
      molecule seems to be needed for these two activities. Our results suggest that
      TAF110 might represent one of the co-activators that mediate transcriptional
      activation by CBF.

PMID- 9512493
TI  - Activation of protein kinase B beta and gamma isoforms by insulin in vivo and by
      3-phosphoinositide-dependent protein kinase-1 in vitro: comparison with protein
      kinase B alpha.
AB  - The regulatory and catalytic properties of the three mammalian isoforms of
      protein kinase B (PKB) have been compared. All three isoforms (PKBalpha, PKBbeta
      and PKBgamma) were phosphorylated at similar rates and activated to similar
      extents by 3-phosphoinositide-dependent protein kinase-1 (PDK1). Phosphorylation
      and activation of each enzyme required the presence of PtdIns(3,4,5)P3 or
      PtdIns(3,4)P2, as well as PDK1. The activation of PKBbeta and PKBgamma by PDK1
      was accompanied by the phosphorylation of the residues equivalent to Thr308 in
      PKBalpha, namely Thr309 (PKBbeta) and Thr305 (PKBgamma). PKBgamma which had been
      activated by PDK1 possessed a substrate specificity identical with that of
      PKBalpha and PKBbeta towards a range of peptides. The activation of PKBgamma and
      its phosphorylation at Thr305 was triggered by insulin-like growth factor-1 in
      293 cells. Stimulation of rat adipocytes or rat hepatocytes with insulin induced
      the activation of PKBalpha and PKBbeta with similar kinetics. After stimulation
      of adipocytes, the activity of PKBbeta was twice that of PKBalpha, but in
      hepatocytes PKBalpha activity was four-fold higher than PKBbeta. Insulin induced
      the activation of PKBalpha in rat skeletal muscle in vivo, with little activation
      of PKBbeta. Insulin did not induce PKBgamma activity in adipocytes, hepatocytes
      or skeletal muscle, but PKBgamma was the major isoform activated by insulin in
      rat L6 myotubes (a skeletal-muscle cell line).

PMID- 9512494
TI  - A human homologue of Escherichia coli ClpP caseinolytic protease: recombinant
      expression, intracellular processing and subcellular localization.
AB  - We have recently cloned a human cDNA (hClpP) with significant sequence similarity
      to the ATP-dependent Escherichia coli ClpP protease [Bross, Andresen, Knudsen,
      Kruse and Gregersen (1995) FEBS Lett. 377, 249-252]. In the present study,
      synthesis, intracellular processing and subcellular localization of hClpP have
      been analysed in intact cells and in a cell-free system. Using pulse
      labelling/immunoprecipitation of Chang cells transfected with the hClpP cDNA, we
      observed two major bands with apparent molecular masses of approx. 39 and 37 kDa.
      A pulse-chase experiment showed that these bands were converted into one mature
      enzyme band with a molecular mass of approx. 32 kDa that was stable for at least
      24 h. The 37 kDa band co-migrated with a band produced upon expression of full
      length hClpP in E. coli, and the 32 kDa band co-migrated with the product of E.
      coli-expressed hClpP in which the 56 N-terminal residues had been deleted,
      indicating that the 37 kDa moiety represents the precursor and that approx. 56
      residues are cleaved off during maturation. The processing of hClpP in intact
      cells was dependent on mitochondrial membrane potential. These results were
      confirmed in an import assay system using in vitro transcription and translation
      directed by the hClpP cDNA and isolated rat liver mitochondria. No protease
      activity towards a series of fluorogenic peptides could be observed in extracts
      of Chang cells overexpressing hClpP, indicating that the protease may not be
      active without co-factors. Immunofluorescence studies using confocal-laser
      scanning microscopy showed co-localization of the hClpP and the mitochondrially
      located Hsp60 (heat-shock protein 60). Taken together, the results reported here
      show that hClpP is localized inside mitochondria and that the trafficking and
      processing of hClpP resembles the typical biogenesis pathway for nuclear-encoded
      mitochondrial proteins.

PMID- 9512495
TI  - Mitsugumin29, a novel synaptophysin family member from the triad junction in
      skeletal muscle.
AB  - In skeletal muscle, excitation-contraction (E-C) coupling requires the conversion
      of the depolarization signal of the invaginated surface membrane, namely the
      transverse (T-) tubule, to Ca2+ release from the sarcoplasmic reticulum (SR).
      Signal transduction occurs at the junctional complex between the T-tubule and SR,
      designated as the triad junction, which contains two components essential for E-C
      coupling, namely the dihydropyridine receptor as the T-tubular voltage sensor and
      the ryanodine receptor as the SR Ca2+-release channel. However, functional
      expression of the two receptors seemed to constitute neither the signal
      transduction system nor the junction between the surface and intracellular
      membranes in cultured cells, suggesting that some as-yet-unidentified molecules
      participate in both the machinery. In addition, the molecular basis of the
      formation of the triad junction is totally unknown. It is therefore important to
      examine the components localized to the triad junction. Here we report the
      identification using monoclonal antibody and primary structure by cDNA cloning of
      mitsugumin29, a novel transmembrane protein from the triad junction in skeletal
      muscle. This protein is homologous in amino acid sequence and shares
      characteristic structural features with the members of the synaptophysin family.
      The subcellular distribution and protein structure suggest that mitsugumin29 is
      involved in communication between the T-tubular and junctional SR membranes.

PMID- 9512496
TI  - Susceptibility of the cysteine-rich N-terminal and C-terminal ends of rat
      intestinal mucin muc 2 to proteolytic cleavage.
AB  - The present study reveals that partial proteolytic degradation of rat Muc 2 mucin
      can occur rapidly even in the presence of a battery of proteinase inhibitors.
      During the initial steps of purification from homogenates of intestinal
      scrapings, degradation was rapid, causing release of the entire 118 kDa C
      terminal glycopeptide and, as shown by N-terminal sequencing, a large (200 kDa) N
      terminal glycopeptide fragment. Degradation could be prevented by adding 6 M
      guanidinium chloride provided that its presence was maintained throughout every
      step of purification. Even after purification, however, the mucin was still
      vulnerable to partial proteolysis unless it was stored in guanidinium chloride at
      -20 degrees C. These findings imply that a potent proteinase contaminant remains
      tightly bound to the mucin through every step of purification, or else that the
      mucin has autocatalytic properties. Because the C- and N-terminal regions of
      secretory mucins are required for their assembly into linear mucin polymers that
      form functional gels, our findings emphasize that extreme care is required to
      purify structurally intact mucin molecules. They also imply that the specific
      degradation steps described here are likely to occur rapidly after mucins are
      secreted into the intestinal lumen and come into contact with the products of
      sloughed cells.

PMID- 9512497
TI  - Functional expression of TrpC1: a human homologue of the Drosophila Trp channel.
AB  - TrpC1 appears to be a store-operated channel (SOC) when expressed in mammalian
      cells. In the present study, TrpC1 was expressed in Sf9 insect cells using the
      baculovirus expression system. Expression of TrpC1 caused an increase in basal
      cytosolic free Ca2+ concentration ([Ca2+]i) as a function of post-infection time.
      Basal Ba2+ influx, an index of plasmalemmal Ca2+ permeability, was also increased
      and was blocked by La3+. Although the thapsigargin-induced change in [Ca2+]i was
      greater in TrpC1-expressing cells than controls, Ba2+ influx was unaffected by
      thapsigargin. Whole-cell membrane currents recorded in TrpC1-expressing cells
      increased as a function of post-infection time and were (1) inwardly rectifying
      in symmetrical sodium gluconate solutions, (2) non-selective with respect to Na+,
      Ca2+ and Ba2+, and (3) blocked by La3+. Furthermore TrpC1 currents were
      unaffected by (1) thapsigargin, (2) dialysis of the cell with Ins(1,4,5)P3 or (3)
      dialysis of the cell with solutions containing high concentrations of the Ca2+
      chelator, EGTA. These results suggest that TrpC1 forms non-selective cation
      channels that are constitutively active when expressed in Sf9 cells, but
      insensitive to depletion of the internal Ca2+ stores. Thus TrpC1 may be a subunit
      of a SOC which alone can form functional channels in Sf9 cells, but which
      requires additional subunits or cytoplasmic factors present in mammalian cells
      for expression of SOC activity.

PMID- 9512499
TI  - Endocytic internalization in yeast and animal cells: similar and different.
AB  - The internalization step of endocytosis has been the focus of several
      laboratories during the last forty years. Unlike some other budding events in the
      cell, many fundamental questions regarding the molecular machinery involved in
      the mechanism of budding itself still remain unsolved. Over the last few years
      the general picture of the field has quickly evolved from the originally
      simplistic view which postulated that clathrin polymerization is the major force
      driving budding at the plasma membrane. Refinement of the assays and molecular
      markers to measure endocytosis in animal cells has shown that other factors in
      addition to the clathrin coat are required and that endocytosis can also take
      place through clathrin-independent mechanisms. At the same time, recent
      introduction of genetic approaches to study endocytosis has accelerated the
      identification of molecules required for this process. The isolation of
      endocytosis mutants in budding yeast has been especially fruitful in this
      respect. Preliminary comparison of the results obtained in yeast and animal cells
      did not seem to coincide, but further progress in both systems now suggests that
      part of the divergence originally seen may be due to the particular experimental
      approaches used rather than fundamental differences in endocytic mechanisms. In
      this review we present a short historical overview on the advances made in yeast
      and animal cells regarding the study of endocytosis, underlining both emerging
      similarities and still interesting differences.

PMID- 9512498
TI  - Cloning of the gene for interstitial collagenase-3 (matrix metalloproteinase-13)
      from rabbit synovial fibroblasts: differential expression with collagenase-1
      (matrix metalloproteinase-1).
AB  - Cartilage, bone and the interstitial stroma, composed largely of the interstitial
      collagens, types I, II and III, are remodelled by three members of the
      metalloproteinase (MMP) family, collagenase-1 (MMP-1), collagenase-2 (MMP-8) and
      collagenase-3 (MMP-13). MMP-1 and MMP-13 may contribute directly to disease
      progression, since they are induced in patients with rheumatoid arthritis and
      osteoarthritis. The study of MMP-1 and MMP-13 gene regulation in models of
      arthritic disease has been problematic because mice and rats, which are typically
      used, only possess a homologue of MMP-13. Here we show that in contrast with mice
      and rats, rabbits possess distinct genes homologous to human MMP-1 and MMP-13.
      Furthermore, rabbit MMP-13 is expressed simultaneously with MMP-1 in chondrocytes
      and synovial fibroblasts in response to the cytokines interleukin-1 and tumour
      necrosis factor-alpha, or the phorbol ester PMA. The time course of MMP-13
      induction is more rapid and transient than that of MMP-1, suggesting that
      distinct mechanisms regulate the expression of these two collagenases. We have
      cloned the rabbit MMP-13 gene from synovial fibroblasts and demonstrated that the
      rabbit gene shares greater homology with human MMP-13 than does the mouse
      interstitial collagenase. Together with the fact that mice and rats do not
      possess a homologue to human MMP-1, our data suggest that the rabbit provides an
      appropriate model for studying the roles of interstitial collagenases in
      connective-tissue diseases, such as rheumatoid arthritis and osteoarthritis.

PMID- 9512500
TI  - Modulation of hepatocyte growth factor-induced scattering of HT29 colon carcinoma
      cells. Involvement of the MAPK pathway.
AB  - Hepatocyte growth factor (HGF)/scatter factor modulates the motility of HT29
      colon carcinoma cells in vitro by inducing morphological changes that depend on
      the type of extra-cellular matrix (ECM) ligand; HGF-induced scattering of HT29
      cells is observed if cells are grown on plastic coated with serum proteins but
      not laminin. The absence of scattering correlates with a lack of cell spreading
      on laminin and it is not due to impaired HGF induced tyrosine phosphorylation of
      the E-cadherin/desmosome component, (gamma)-catenin, or lack of activation of
      mitogen activated protein kinase (MAPK). Treatment of HT29 cells with phorbol 12
      myristate, 13-acetate (PMA), but not arachidonic acid, restored the ability of
      the cells to spread on laminin in an integrin-dependent manner. Moreover, the
      addition of both PMA and HGF restored the ability of these cells to scatter on
      laminin in a synergistic manner. This event correlated with increased tyrosine
      phosphorylation of paxillin and activation of MAPK. Moreover, when the MEK (MAPK
      kinase)/MAPK pathway was blocked by the MEK inhibitor PD098059, HGF-induced
      scattering of HT29 cells was blocked. Thus, HGF modulation of HT29 cell motility
      is regulated by both integrin and growth factor-dependent signaling and
      implicates MAPK in the modulation of intercellular adhesion and epithelial cell
      motility.

PMID- 9512501
TI  - Cornified cell envelope assembly: a model based on electron microscopic
      determinations of thickness and projected density.
AB  - In stratifying squamous epithelia, the cornified cell envelope (CE), a peripheral
      layer of crosslinked protein, is assembled sequentially from precursor proteins
      initially dispersed in the cytoplasm. Its major component is loricrin (37 kDa in
      mouse), which contributes from approx. 60% to >80% of the protein mass in
      different tissues. Despite its importance to the mechanical resilience and
      impenetrability of these tissues, detailed information has not been obtained on
      CE structure, even on such basic properties as its thickness or uniformity across
      a given CE or from tissue to tissue. To address this issue, we have studied CEs
      isolated from three murine epithelia, namely epidermis, forestomach and footpad,
      by electron microscopy of metal-shadowed specimens and scanning transmission
      electron microscopy (STEM) of unstained specimens. The former data reveal that
      the cytoplasmic surface is smoothly textured whereas the extracellular surface is
      corrugated, and that the average thickness is 15.3+/-1.2 nm, and strikingly
      uniform. Measurements of mass-per-unit-area from the STEM images yielded values
      of approx. 7.0+/-0.8 kDa/nm2, which were remarkably consistent over all three
      tissues. These data imply that the mature CE has a uniquely defined thickness. To
      explain its uniformity, we postulate that loricrin forms a molecular monolayer,
      not a variable number of multiple layers. In this scenario, the packing density
      is one loricrin monomer per 7 nm2, and loricrin should have an elongated shape,
      2.5-3.0 nm wide by approx. 11 nm long. Moreover, we anticipate that any inter
      tissue variations in the mechanical properties of CEs should depend more on
      protein composition and cross-linking pattern than on the thickness of the
      protein layer deposited.

PMID- 9512503
TI  - E-cadherin mediated cell adhesion recruits SAP97 into the cortical cytoskeleton.
AB  - Members of the SAP family of synapse-associated proteins have recently emerged as
      central players in the molecular organization of synapses. In this study, we have
      examined the mechanism that localizes one member, SAP97, to sites of cell-cell
      contact. Utilizing epithelial CACO-2 cells and fibroblast L-cells as model
      systems, we demonstrate that SAP97 is associated with the submembranous cortical
      cytoskeleton at cell-cell adhesion sites. Furthermore, we show that its
      localization into this structure is triggered by E-cadherin. Although SAP97 can
      be found in an E-cadherin/catenin adhesion complex, this interaction seems to be
      mediated by the attachment of SAP97 to the cortical cytoskeleton. Our results are
      consistent with a model in which SAP97 is recruited to sites of cell-cell contact
      via an E-cadherin induced assembly of the cortical cytoskeleton.

PMID- 9512502
TI  - A novel Rab GTPase, Rab33B, is ubiquitously expressed and localized to the medial
      Golgi cisternae.
AB  - Small GTP-binding proteins of the Rab family play important roles at defined
      steps of vesicular transport in protein secretion and the endocytosis pathway. In
      mammals, more than 30 proteins belonging to the Rab family have been reported to
      date. We report here the molecular cloning and characterization of a novel Rab
      protein, Rab33B. The amino acid sequence of Rab33B shows 55.3% identity to the
      Rab33A protein (previously called S10), and these two proteins share unique amino
      acid sequences at the effector domain. The genomic organization of rab33B was the
      same as rab33A: it consists of two exons. Thus, these two proteins make a
      subclass within the Rab family. Northern blot analysis showed that rab33B is
      expressed ubiquitously in mouse tissues, in contrast to rab33A whose expression
      is restricted to the brain and the immune system. A 26 kDa protein was detected
      by western blotting using a Rab33B-specific monoclonal antibody. Using
      immunofluorescence studies, Rab33B was shown to co-localize with (alpha)
      mannosidase II, a Golgi-specific marker. Immunoelectron microscopy analysis
      further defined the localization of Rab33B to the medial Golgi cisternae. These
      results suggest Rab33B plays a role in intra-Golgi transport.

PMID- 9512504
TI  - Reversal of myogenic terminal differentiation by SV40 large T antigen results in
      mitosis and apoptosis.
AB  - Terminally differentiated skeletal muscle myotubes are arrested in the G0 phase
      of the cell cycle, and this arrest is not reversed by stimulation with serum or
      growth factors. The myotubes have been shown to be refractory to apoptosis even
      under low serum conditions. When the SV40 large T antigen is induced in the
      C2SVTts11 myotubes, which stably harbor the T antigen gene linked to an inducible
      promoter, the terminally differentiated cells reenter the cell cycle to resume
      nuclear DNA replication representing S phase. We show here that the large T
      expressing myotubes further proceeded to M phase represented by the appearance of
      mitotic figures with centrosomes, condensed chromosomes, and mitotic spindles.
      The myotubes eventually cleaved and midbodies were formed at the cleavage sites
      of the cytoplasm. In some cases actin filaments, reminiscent of the contractile
      rings, accumulated at the cleavage furrows. Thus, terminally differentiated
      myotubes remain able to resume at least one round of the cell cycle and
      consequently are considered to be capable of dedifferentiation. A subset of
      myotubes expressing large T did not undergo mitosis. Some of them were
      degenerative and contained deformed giant nuclei and pulverized nuclei. The
      others suffered apoptotic cell death, which was identified by morphological
      changes of the nuclei and the labeling with dUTP at the ends of chromatin DNA
      fragments. The induction of apoptosis was unlikely to be confined to a particular
      phase of the cell cycle. These results imply that terminally differentiated
      myotubes also retain a complete set of machinery for apoptosis.

PMID- 9512505
TI  - Domains of tenascin involved in glioma migration.
AB  - Tenascin (TN) is an extracellular matrix protein found in areas of cell migration
      during development and expressed at high levels in migratory tumor cells. TN was
      previously shown to support the attachment and migration of glioma cells in
      culture. To determine the domains responsible for glioma migration and
      attachment, we produced recombinant fusion proteins that collectively span the
      majority of the molecule including its epidermal growth factor-like repeats,
      fibronectin type III repeats and fibrinogen domain. These domains were tested for
      their ability to support migration of C6 glioma cells in an aggregate migration
      assay. A recombinant fusion protein including fibronectin type III (FNIII)
      repeats 2-6 (TNfn2-6) was the only fragment found to promote migration of C6
      glioma cells at levels similar to that promoted by intact TN. Evaluation of
      smaller segments and individual FNIII repeats revealed that TNfn3 promoted
      migration and attachment of glioma cells and TNfn6 promoted migration but not
      attachment. While TNfn3 and TNfn6 promoted migration individually, the presence
      of both TNfn3 and TNfn6 was required for migration on segments of the FNIII
      region that included TNfn5. TNfn5 inhibited migration in a dose dependent manner
      when mixed with TNfn3 and also promoted strong attachment and spreading of C6
      glioma cells. TNfn3 and TNfn6 promote cell migration and may function
      cooperatively to overcome the inhibitory activity of TNfn5. Additional cell
      attachment studies suggested that both beta1 integrins and heparin may
      differentially influence the attachment of glioma cells to TN fragments.
      Together, these findings show that C6 glioma cells integrate their response upon
      binding to at least three domains within TN.

PMID- 9512506
TI  - Proteasomes regulate the motility of salmonid fish sperm through modulation of
      cAMP-dependent phosphorylation of an outer arm dynein light chain.
AB  - Proteasomes are involved in ATP-dependent regulation of sperm motility in
      salmonid fish. We have demonstrated here by immunoelectron microscopy that
      proteasomes are located at the structure of the chum salmon sperm flagellum that
      attaches at the base of the outer arm dynein and extends toward the plasma
      membrane. Furthermore, substrates and inhibitors of proteasome inhibit the cAMP
      dependent phosphorylation of a 22 kDa axonemal protein in chum salmon sperm. The
      22 kDa phosphoprotein was solubilized by treatment of the axoneme with a high
      salt solution and subsequent sucrose density gradient centrifugation of the
      extract revealed that it cosedimented with 19 S outer arm dynein, indicating that
      it is a dynein light chain. These results suggest that proteasomes modulate the
      activity of outer arm dynein by regulating cAMP-dependent phosphorylation of the
      22 kDa dynein light chain.

PMID- 9512507
TI  - Mutational analysis of the potential phosphorylation sites in the cytoplasmic
      domain of integrin beta1A. Requirement for threonines 788-789 in receptor
      activation.
AB  - To investigate the role of the potential phosphorylation sites in the cytoplasmic
      domain of integrin beta1A, point mutated variants of the protein were stably
      expressed in the beta1-deficient cell line GD25. Mutants T777A, Y783F, S785A, and
      Y795F were fully active in promoting cell adhesion, de novo formation of focal
      contacts, formation of fibronectin fibrils, and activation of focal adhesion
      kinase. Thus, phosphorylation of these residues is not required for several basic
      functions of integrin beta1A. On the other hand, the TT788-9AA mutant, was
      defective in mediating cell attachment and did not contribute to fibronectin
      fibril formation. The conformation of the extracellular domain was shifted
      towards an inactive state as measured by binding of the monoclonal antibody 9EG7.
      Antibody induced clustering of beta1ATT788-9AA demonstrated that the mutant
      cytoplasmic part was functional in mediating activation of focal adhesion kinase.
      Therefore, we conclude that threonines 788-789, which are conserved among most
      integrin beta subunits, are of critical importance for integrin function due to
      effects on the extracellular conformation of the receptor.

PMID- 9512508
TI  - Effects of collagenase-cleavage of type I collagen on alpha2beta1 integrin
      mediated cell adhesion.
AB  - In this paper we show that collagenase-3 cleavage of type I collagen has a marked
      effect on alpha2beta1 integrin-mediated interactions with the collagen fragments
      generated. Isolated alpha2beta1 integrin and alpha2 integrin A-domain were found
      to bind to both native collagen and native 3/4 fragment and, to a lesser degree,
      native 1/4 fragment. Whole integrin and integrin A-domain binding were lost after
      heat denaturation of the collagen fragments. At physiological temperature, cell
      adhesion to triple-helical 3/4 fragment via alpha2beta1 integrin was still
      possible; however, no alpha2beta1 integrin-mediated adhesion to the 1/4 fragment
      was observed. Unwinding of the collagen fragment triple helices by heating to
      physiological temperatures prior to adsorption to plastic tissue culture plates
      resulted in total abrogation of HT1080 cell attachment to either fragment. These
      results provide significant evidence in support of a role for matrix
      metalloproteinase cleavage of the extracellular matrix in modifying cell-matrix
      interactions.

PMID- 9512509
TI  - Cyclic AMP stimulates sorting of the canalicular organic anion transporter
      (Mrp2/cMoat) to the apical domain in hepatocyte couplets.
AB  - The canalicular membrane of rat hepatocytes contains an ATP-dependent
      multispecific organic anion transporter, also named multidrug resistance protein
      2, that is responsible for the biliary secretion of several amphiphilic organic
      anions. This transport function is markedly diminished in mutant rats that lack
      the transport protein. To assess the role of vesicle traffic in the regulation of
      canalicular organic anion transport, we have examined the redistribution of the
      transporter to the canalicular membrane and the effect of cAMP on this process in
      isolated hepatocyte couplets, which retain secretory polarity. The partial
      disruption of cell-cell contact, due to the isolation procedure, leaves the
      couplet with both remnant apical membranes, as a source of apical proteins, and
      an intact apical domain and lumen, to which these proteins are targeted. The
      changes in distribution of the transporter were correlated to the apical
      excretion of a fluorescent substrate, glutathione-methylfluorescein. The data
      obtained in this study show that the transport protein, endocytosed from apical
      membrane remnants, first is redistributed along the basolateral plasma membrane.
      Then it is transcytosed to the remaining apical pole in a microtubule-dependent
      fashion, followed by the fusion of transporter-containing vesicles with the
      apical membrane. The cAMP analog dibutyrylcAMP stimulates all three steps,
      resulting in increased apically located transport protein, glutathione
      methylfluorescein transport activity and apical membrane circumference. These
      findings indicate that the organic anion transport capacity of the apical
      membrane in hepatocyte couplets is regulated by cAMP-stimulated sorting of the
      multidrug resistance protein 2 to the apical membrane. The relevance of this
      phenomenon for the intact liver is discussed.

PMID- 9512510
TI  - The compulsion of chirality: toward an understanding of left-right asymmetry.

PMID- 9512511
TI  - Pyk2 is a downstream mediator of the IL-2 receptor-coupled Jak signaling pathway.
AB  - Many cytokines transmit signals to the cell interior through activation of
      receptor-associated, Janus family protein tyrosine kinases (Jak PTKs). The
      interleukin-2 receptor (IL-2R) is associated with the Jak1 and Jak3 PTKs, and
      ligand-induced activation of these PTKs is essential for lymphocyte
      proliferation. Here, the nonreceptor PTK, Pyk2, was found to be activated
      following IL-2 stimulation in a Jak-dependent manner. Furthermore, physical
      association was detected between endogenous Pyk2 and Jak3, and a dominant
      interfering mutant of Pyk2 inhibited IL-2-induced cell proliferation without
      affecting Stat5 activation. Collectively, these results suggest that Pyk2 is a
      newly identified component of the Jak-mediated IL-2 signaling pathway.

PMID- 9512512
TI  - Sox1 directly regulates the gamma-crystallin genes and is essential for lens
      development in mice.
AB  - gamma-Crystallins are major structural components of the lens fiber cells in
      amphibians and mammals. Many dominant inherited cataracts in humans and mice have
      been shown to map within the gamma-crystallin gene cluster. Several transcription
      factors, including PAX6 and SOX proteins, have been suggested as candidates for
      crystallin gene regulation. Here we show that the targeted deletion of Sox1 in
      mice causes microphthalmia and cataract. Mutant lens fiber cells fail to
      elongate, probably as a result of an almost complete absence of gamma
      crystallins. It appears that the direct interaction of the SOX1 protein with a
      promoter element conserved in all gamma-crystallin genes is responsible for their
      expression.

PMID- 9512513
TI  - Helios, a T cell-restricted Ikaros family member that quantitatively associates
      with Ikaros at centromeric heterochromatin.
AB  - The Ikaros gene encodes multiple protein isoforms that contribute critical
      functions during the development of lymphocytes and other hematopoietic cell
      types. The intracellular functions of Ikaros are not known, although recent
      studies have shown that Ikaros proteins colocalize with inactive genes and
      centromeric heterochromatin. In this study, Ikaros proteins were found to be
      components of highly stable complexes. The complexes from an immature T cell line
      were purified, revealing associated proteins of 70 and 30 kD. The p70 gene, named
      Helios, encodes two protein isoforms with zinc finger domains exhibiting
      considerable homology to those within Ikaros proteins. Helios and Ikaros
      recognize similar DNA sequences and, when overexpressed, Helios associates
      indiscriminately with the various Ikaros isoforms. Although Ikaros is present in
      most hematopoietic cells, Helios was found primarily in T cells. The relevance of
      the Ikaros-Helios interaction in T cells is supported by the quantitative
      association of Helios with a fraction of the Ikaros. Interestingly, the Ikaros
      Helios complexes localize to the centromeric regions of T cell nuclei, similar to
      the Ikaros localization previously observed in B cells. Unlike the B cell
      results, however, only a fraction of the Ikaros, presumably the fraction
      associated with Helios, exhibited centromeric localization in T cells. These
      results establish immunoaffinity chromatography as a useful method for
      identifying Ikaros partners and suggest that Helios is a limiting regulatory
      subunit for Ikaros within centromeric heterochromatin.

PMID- 9512514
TI  - Histone deacetylase activity of Rpd3 is important for transcriptional repression
      in vivo.
AB  - Eukaryotic organisms from yeast to human contain a multiprotein complex that
      includes Rpd3 histone deacetylase and Sin3 corepressor. The Sin3-Rpd3 complex,
      when recruited to promoters by specific DNA-binding proteins, can direct
      transcriptional repression of specific classes of target genes. It has been
      proposed that the histone deacetylase activity of Rpd3 is important for
      repression, but direct evidence is lacking. Here, we describe four Rpd3
      derivatives with mutations in evolutionarily invariant histidine residues in a
      putative deacetylation motif. These Rpd3 mutants lack detectable histone
      deacetylase activity in vitro, but interact normally with Sin3 in vivo. In yeast
      cells, these catalytically inactive mutants are defective for transcriptional
      repression. They retain some residual Rpd3 function in vivo, however, suggesting
      that repression by the Sin3-Rpd3 complex may not be attributable exclusively to
      its intrinsic histone deacetylase activity. Finally, we show that a human Rpd3
      homolog can interact with yeast Sin3 and repress transcription when artificially
      recruited to a promoter. These results suggest that the histone deacetylase
      activity of Rpd3 is important, but perhaps not absolutely required, for
      transcriptional repression in vivo.

PMID- 9512516
TI  - The basic helix-loop-helix protein BETA2 interacts with p300 to coordinate
      differentiation of secretin-expressing enteroendocrine cells.
AB  - The major epithelial cell types lining the intestine comprise a perpetually self
      renewing population of cells that differentiate continuously from a stem cell in
      the intestinal crypts. Secretin-producing enteroendocrine cells represent a
      nondividing subpopulation of intestinal epithelial cells, suggesting that
      expression of the hormone is coordinated with cell cycle arrest during the
      differentiation of this cell lineage. Here we report that the basic helix-loop
      helix protein BETA2 associates functionally with the coactivator, p300 to
      activate transcription of the secretin gene as well as the gene encoding the
      cyclin-dependent kinase inhibitor p21. Overexpression of BETA2 in cell lines
      induces both cell cycle arrest and apoptosis suggesting that BETA2 may regulate
      proliferation of secretin cells. Consistent with this role, we observed both
      reentry of normally quiescent cells into the cell cycle and disrupted cell number
      regulation in the small intestine of BETA2 null mice. Thus, BETA2 may function to
      coordinate transcriptional activation of the secretin gene, cell cycle arrest,
      and cell number regulation, providing one of the first examples of a
      transcription factor that controls terminal differentiation of cells in the
      intestinal epithelium.

PMID- 9512515
TI  - Essential contribution of caspase 3/CPP32 to apoptosis and its associated nuclear
      changes.
AB  - Caspases are fundamental components of the mammalian apoptotic machinery, but the
      precise contribution of individual caspases is controversial. CPP32 (caspase 3)
      is a prototypical caspase that becomes activated during apoptosis. In this study,
      we took a comprehensive approach to examining the role of CPP32 in apoptosis
      using mice, embryonic stem (ES) cells, and mouse embryonic fibroblasts (MEFs)
      deficient for CPP32. CPP32(ex3-/-) mice have reduced viability and, consistent
      with an earlier report, display defective neuronal apoptosis and neurological
      defects. Inactivation of CPP32 dramatically reduces apoptosis in diverse
      settings, including activation-induced cell death (AICD) of peripheral T cells,
      as well as chemotherapy-induced apoptosis of oncogenically transformed CPP32(-/-)
      MEFs. As well, the requirement for CPP32 can be remarkably stimulus-dependent: In
      ES cells, CPP32 is necessary for efficient apoptosis following UV- but not gamma
      irradiation. Conversely, the same stimulus can show a tissue-specific dependence
      on CPP32: Hence, TNFalpha treatment induces normal levels of apoptosis in CPP32
      deficient thymocytes, but defective apoptosis in oncogenically transformed MEFs.
      Finally, in some settings, CPP32 is required for certain apoptotic events but not
      others: Select CPP32(ex3-/-) cell types undergoing cell death are incapable of
      chromatin condensation and DNA degradation, but display other hallmarks of
      apoptosis. Together, these results indicate that CPP32 is an essential component
      in apoptotic events that is remarkably system- and stimulus-dependent.
      Consequently, drugs that inhibit CPP32 may preferentially disrupt specific forms
      of cell death.

PMID- 9512517
TI  - Drosophila myb is required for the G2/M transition and maintenance of diploidy.
AB  - The myb proto-oncogenes are thought to have a role in the cell division cycle. We
      have examined this possibility by genetic analysis in Drosophila melanogaster,
      which possesses a single myb gene. We have described previously two temperature
      sensitive, recessive lethal mutants in Drosophila myb (Dm myb). The phenotypes of
      these mutants revealed a requirement for myb in diverse cellular lineages
      throughout the course of Drosophila development. We now report a cellular
      explanation for these findings by showing that Dm myb is required for both
      mitosis and prevention of endoreduplication in wing cells. Myb apparently acts at
      or near the time of the G2/M transition. The two mutant alleles of Dm myb produce
      the same cellular phenotype, although the responsible mutations are located in
      different functional domains of the gene product. The mutant phenotype can be
      partially suppressed by ectopic expression of either cdc2 or string, two genes
      that are known to promote the transition from G2 to M. We conclude that Dm myb is
      required for completion of cell division and may serve two independent functions:
      promotion of mitosis, on the one hand, and prevention of endoreduplication when
      cells are arrested in G2, on the other.

PMID- 9512518
TI  - The type I activin receptor ActRIB is required for egg cylinder organization and
      gastrulation in the mouse.
AB  - ActRIB is a type I transmembrane serine/threonine kinase receptor that has been
      shown to form heteromeric complexes with the type II activin receptors to mediate
      activin signal. To investigate the function of ActRIB in mammalian development,
      we generated ActRIB-deficient ES cell lines and mice by gene targeting. Analysis
      of the ActRIB-/- embryos showed that the epiblast and the extraembryonic ectoderm
      were disorganized, resulting in disruption and developmental arrest of the egg
      cylinder before gastrulation. To assess the function of ActRIB in mesoderm
      formation and gastrulation, chimera analysis was conducted. We found that ActRIB
      /- ES cells injected into wild-type blastocysts were able to contribute to the
      mesoderm in chimeric embryos, suggesting that ActRIB is not required for mesoderm
      formation. Primitive streak formation, however, was impaired in chimeras when
      ActRIB-/- cells contributed highly to the epiblast. Further, chimeras generated
      by injection of wild-type ES cells into ActRIB-/- blastocysts formed relatively
      normal extraembryonic tissues, but the embryo proper developed poorly probably
      resulting from severe gastrulation defect. These results provide genetic evidence
      that ActRIB functions in both epiblast and extraembryonic cells to mediate
      signals that are required for egg cylinder organization and gastrulation.

PMID- 9512519
TI  - A cooperative interaction between U2AF65 and mBBP/SF1 facilitates branchpoint
      region recognition.
AB  - During the early events of pre-mRNA splicing, intronic cis-acting sequences are
      recognized and interact through a network of RNA-RNA, RNA-protein, and protein
      protein contacts. Recently, we identified a branchpoint sequence binding protein
      in yeast (BBP). The mammalian ortholog (mBBP/SF1) also binds specifically to
      branchpoint sequences and interacts with the well studied mammalian splicing
      factor U2AF65, which binds to the adjacent polypyrimidine (PY) tract. In this
      paper we demonstrate that the mBBP/SF1-U2AF65 interaction promotes cooperative
      binding to a branchpoint sequence-polypyrimidine tract-containing RNA, and we
      suggest that this cooperative RNA binding contributes to initial recognition of
      the branchpoint sequence (BPS) during pre-mRNA splicing. We also demonstrate the
      essential nature of the third RBD of U2AF65 for the interaction between the two
      proteins, both in the presence and absence of RNA.

PMID- 9512520
TI  - ICP27 mediates HSV RNA export by shuttling through a leucine-rich nuclear export
      signal and binding viral intronless RNAs through an RGG motif.
AB  - Infection of metazoan cells with some viruses alters the balance of cellular mRNA
      export to favor viral RNA export and to retain cellular transcripts in the
      nucleus. Here, evidence is presented to show that the herpes simplex virus 1 (HSV
      1) essential regulatory protein ICP27, which inhibits host cell-splicing,
      resulting in the accumulation of unspliced transcripts in the nucleus, mediates
      RNA export of viral intronless mRNAs. ICP27 was shown to shuttle between the
      nucleus and cytoplasm through a leucine-rich nuclear export signal, which alone
      was able to direct the export of the heterologous green fluorescent protein. In
      vivo UV irradiation studies demonstrated that ICP27 could be crosslinked to
      poly(A)+ RNA in the nucleus and the cytoplasm, supporting a role in export.
      Furthermore, the amount of hnRNP A1, which has been implicated in the export of
      cellular spliced mRNAs, that was bound to poly(A)+ RNA in HSV-1-infected cells
      was reduced compared with uninfected cells. In addition, it was demonstrated that
      ICP27 bound seven intronless HSV-1 transcripts in both the nucleus and the
      cytoplasm, and export of these transcripts was diminished substantially during
      infection with an ICP27 null mutant virus. In contrast, ICP27 did not bind to two
      HSV-1 mRNAs that undergo splicing. Finally, binding of ICP27 to RNA in vivo
      required an arginine-glycine region that resembles an RGG box. These results
      indicate that ICP27 is an important viral export factor that promotes the
      transport of HSV-1 intronless RNAs.

PMID- 9512521
TI  - Cell cycle-dependent transcriptional and proteolytic regulation of FtsZ in
      Caulobacter.
AB  - In the differentiating bacterium Caulobacter crescentus, the cell division
      initiation protein FtsZ is present in only one of the two cell types. Stalked
      cells initiate a new round of DNA replication immediately after cell division and
      contain FtsZ, whereas the progeny swarmer cells are unable to initiate DNA
      replication and do not contain FtsZ. We show that FtsZ expression is controlled
      by cell cycle-dependent transcription and proteolysis. Transcription of ftsZ is
      repressed in swarmer cells and is activated concurrently with the initiation of
      DNA replication. At the end of the DNA replication period, transcription of ftsZ
      decreases substantially. We show that the global cell cycle regulator CtrA is
      involved in the cell cycle control of ftsZ transcription. CtrA binds to a site
      that overlaps the ftsZ transcription start site. Removal of the CtrA-binding site
      results in transcription of the ftsZ promoter in swarmer cells. Decreasing the
      cellular concentration of CtrA increases ftsZ transcription and conversely,
      increasing the concentration of CtrA decreases ftsZ transcription. Because CtrA
      is present in swarmer cells, is degraded at the same time as ftsZ transcription
      begins, and reappears when ftsZ transcription decreases at the end of the cell
      cycle, we propose that CtrA is a repressor of ftsZ transcription. We show that
      proteolysis is an important determinant of cell type-specific distribution and
      cell cycle variation of FtsZ. FtsZ is stable when it is synthesized and assembles
      into the cytokinetic ring at the beginning of the cell cycle. After the
      initiation of cell division, the rate of FtsZ degradation increases as both the
      constriction site and the FtsZ ring decrease in diameter. When ftsZ is expressed
      constitutively from inducible promoters, the abundance of FtsZ still varies
      during the cell cycle. The coupling of transcription and proteolysis to cell
      division ensures that FtsZ is inherited only by the progeny cell that will begin
      DNA replication immediately after cell division.

PMID- 9512522
TI  - A protein-induced DNA bend increases the specificity of a prokaryotic enhancer
      binding protein.
AB  - Control of transcription in prokaryotes often involves direct contact of
      regulatory proteins with RNA polymerase from binding sites located adjacent to
      the target promoter. Alternatively, in the case of genes transcribed by
      Escherichia coli RNA polymerase holoenzyme containing the alternate sigma factor
      sigma54, regulatory proteins bound at more distally located enhancer sites can
      activate transcription via DNA looping by taking advantage of the increasing
      flexibility of DNA over longer distances. While this second mechanism offers a
      greater possible flexibility in the location of these binding sites, it is not
      clear how the specificity offered by the proximity of the regulatory protein and
      the polymerase intrinsic to the first mechanism is maintained. Here we
      demonstrate that integration host factor (IHF), a protein that induces a sharp
      bend in DNA, acts both to inhibit DNA-looping-dependent transcriptional
      activation by an inappropriate enhancer-binding protein and to facilitate similar
      activation by an appropriate enhancer-binding protein. These opposite effects
      have the consequence of increasing the specificity of activation of a promoter
      that is susceptible to regulation by proteins bound to a distal site.

PMID- 9512524
TI  - Recognition and manipulation of branched DNA by the RusA Holliday junction
      resolvase of Escherichia coli.
AB  - Homologous recombination is a fundamental cellular process that shapes and
      reshapes the genomes of all organisms and promotes repair of damaged DNA. A key
      step in this process is the resolution of Holliday junctions formed by homologous
      DNA pairing and strand exchange. In Escherichia coli , a Holliday junction is
      processed into recombinant products by the concerted activities of the RuvA and
      RuvB proteins, which together drive branch migration, and RuvC endonuclease,
      which resolves the structure. In the absence of RuvABC, recombination can be
      promoted by increasing the expression of the RusA endonuclease, a Holliday
      junction resolvase encoded by a cryptic prophage gene. Here, we describe the DNA
      binding properties of RusA. We found that RusA was highly selective for branched
      molecules and formed complexes with these structures even in the presence of a
      large excess of linear duplex DNA. However, it does bind weakly to linear duplex
      DNA. Under conditions where there was no detectable binding to duplex DNA, RusA
      formed a highly structured complex with a synthetic Holliday junction that was
      remarkably stable and insensitive to divalent metal ions. The duplex arms were
      found to adopt a specific alignment within this complex that approximated to a
      tetrahedral conformation of the junction.

PMID- 9512523
TI  - Interaction of Ku protein and DNA-dependent protein kinase catalytic subunit with
      nucleic acids.
AB  - The Ku protein-DNA-dependent protein kinase system is one of the major pathways
      by which cells of higher eukaryotes respond to double-strand DNA breaks. The
      components of the system are evolutionarily conserved and homologs are known from
      a number of organisms. The Ku protein component binds directly to DNA ends and
      may help align them for ligation. Binding of Ku protein to DNA also nucleates
      formation of an active enzyme complex containing the DNA-dependent protein kinase
      catalytic subunit (DNA-PKcs). The interaction between Ku protein, DNA-PKcs and
      nucleic acids has been extensively investigated. This review summarizes the
      results of these biochemical investigations and relates them to recent molecular
      genetic studies that reveal highly characteristic repair and recombination
      defects in mutant cells lacking Ku protein or DNA-PKcs.

PMID- 9512525
TI  - Selecting optimal oligonucleotide composition for maximal antisense effect
      following streptolysin O-mediated delivery into human leukaemia cells.
AB  - It is widely accepted that most cell types efficiently exclude oligonucleotides
      in vitro and require specific delivery systems, such as cationic lipids, to
      enhance uptake and subsequent antisense effects. Oligonucleotides are not readily
      transfected into leukaemia cell lines using cationic lipid systems and
      streptolysin O (SLO) is used to effect their delivery. We wished to investigate
      the optimal oligonucleotide composition for antisense efficacy and specificity
      following delivery into leukaemia cells using SLO. For this study the well
      characterised chronic myeloid leukaemia cell line KYO-1 was selected and
      oligonucleotides (20mers) were targeted to an empirically identified accessible
      site of c- myc mRNA. The efficiency and specificity of antisense effect was
      measured 4 and 24 h after SLO-mediated delivery of the oligonucleotides. C5
      propyne phosphodiester and phosphorothioate compounds were found to present
      substantial non-specific effects at 20 microM but were inactive at 0.2 microM.
      Indeed, no antisense-specific effect was noted at any concentration at either
      time. All of the other oligonucleotides tested induced some measurable antisense
      effect, except 7 (chimeric, all-phosphorothioate, 2'-methoxyethoxy termini) which
      was essentially inactive at 20 microM. The rank efficiency order of the remaining
      antisense compounds was 4 = 3 >> 9 >> 10 = 8 = 5 = 6 > 11. The efficient
      antisense effects induced by the chimeric methylphosphonate-phosphodiester
      compounds were found to be highly specific. Increased phosphorothioate content in
      the oligonucleotide backbone correlated with reduced antisense activity
      (efficacy: 2'-methoxyethoxy series 9 >> 8 >> 7, 2'-methoxytriethoxy series 10 >
      11). No consistent evidence was obtained for increased activity correlating with
      increased oligonucleotide-mRNA heteroduplex thermal stability. In conclusion, the
      chimeric methylphosphonate-phosphodiester oligodeoxynucleotides present the most
      favourable characteristics of the compounds tested, for efficient and specific
      antisense suppression of gene expression following SLO-mediated delivery.

PMID- 9512526
TI  - SnoRNA-guided ribose methylation of rRNA: structural features of the guide RNA
      duplex influencing the extent of the reaction.
AB  - Eukaryotic rRNAs contain a large number of ribose-methylated nucleotides of
      elusive function which are confined to the universally conserved rRNA domains.
      Ribose methylation of these nucleotides is directed by a large family of small
      trans -acting guide RNAs, called box C/D antisense snoRNAs. Each snoRNA targets
      precisely one of the nucleotides to be methylated within the pre-rRNA sequence,
      through transient formation of a 10-21 bp regular RNA duplex around the
      modification site. In this study we have analyzed how different features of the
      double-stranded RNA guide structure affect the extent of site-specific ribose
      methylation, by co-expressing an appropriate RNA substrate and its cognate
      tailored snoRNA guide in transfected mouse cells. We show that an increased GC
      content of the duplex can make up for the inhibitory effects of a helix
      truncation or for the presence of helix irregularities such as a mismatched pair
      or a bulge nucleotide. However, some helix irregularities dramatically inhibit
      the reaction and are not offset by further stabilization of the duplex. Overall,
      the RNA duplex tolerates a much larger degree of irregularity than anticipated,
      even in the immediate vicinity of the methylation site, which offers new
      prospects in the search for additional snoRNA guides. Accordingly, a few snoRNA
      like sequences of uncertain status detected in the yeast Saccharomyces cerevisiae
      genome now appear as likely bona fide ribose methylation guides.

PMID- 9512527
TI  - Mechanisms of DNA damage by chromium(V) carcinogens.
AB  - Reactions of bis(2-ethyl-2-hydroxy-butanato)oxochromate(V) with pUC19 DNA, single
      stranded calf thymus DNA (ss-ctDNA), a synthetic oligonucleotide, 5'
      GATCTATGGACTTACTTCAAGGCCGGGTAATGCTA-3' (35mer), deoxyguanosine and guanine were
      carried out in Bis-Tris buffer at pH 7.0. The plasmid DNA was only nicked,
      whereas the single-stranded DNA suffered extensive damage due to oxidation of the
      ribose moiety. The primary oxidation product was characterized as 5-methylene-2
      furanone. Although all four bases (A, C, G and T) were released during the
      oxidation process, the concentration of guanine exceeds the other three.
      Orthophosphate and 3'-phosphates were also detected in this reaction. Likewise,
      the synthetic oliogomer exhibits cleavage at all bases with a higher frequecncy
      at G sites. This increased cleavage at G sites was more apparent after treating
      the primary oxidation products with piperidine, which may indicate base oxidation
      as well. DNA oxidation is shown to proceed through a Cr(V)-DNA intermediate in
      which chromium(V) is coordinated through the phosphodiester moiety. Two
      alternative mechanisms for DNA oxidation by oxochromate(V) are proposed to
      account for formation of 5-methylene-2-furanone, based on hydrogen abstraction or
      hydride transfer from the C1' site of the ribose followed by hydration and two
      successive beta-eliminations. It appears that phosphate coordination is a
      prerequisite for DNA oxidation, since no reactions between chromium(V) and
      deoxyguanosine or guanine were observed. Two other additional pathways, hydrogen
      abstraction from C4' and guanine base oxidation, are also discussed.

PMID- 9512528
TI  - Drosophila clipper/CPSF 30K is a post-transcriptionally regulated nuclear protein
      that binds RNA containing GC clusters.
AB  - An essential component of the mammalian pre-mRNA 3'-end processing machinery is a
      multimeric protein complex known as cleavage and polyadenylation specificity
      factor (CPSF). The Drosophila melanogaster gene, clipper ( clp ), encodes a
      homolog of the CPSF 30K subunit. We have shown previously that CLP possesses N
      terminal endoribonucleolytic activity and that the relative expression of its
      mRNA fluctuates during fly development. In the present study, we report that
      CLP's C-terminus, containing two CCHC zinc knuckles, confers a binding preference
      for RNAs that contain G- and/or C-rich clusters. We also show, for the first
      time, that a member of the highly conserved CPSF 30K family is a nuclear and
      developmentally regulated protein. Though clp transcripts are detectable
      throughout embryogenesis, CLP protein is not present. We demonstrate that post
      transcriptional regulation of clp mRNA in the embryo occurs by a process that
      does not involve poly(A) tail length shortening. Thus, a key component of the pre
      mRNA 3'-end processing machinery is subject to post-transcriptional regulation
      during development. These results support the existence of a distinct mechanism
      controlling eukaryotic gene expression through the regulated processing of pre
      mRNAs in the nucleus.

PMID- 9512529
TI  - A conserved structural element in horse and mouse IGF2 genes binds a methylation
      sensitive factor.
AB  - The equine IGF2 gene has been cloned and characterised. It spans a 9 kb region,
      which is substantially less than the corresponding human gene. Three coding exons
      and three untranslated leader exons, all highly homologous to those in other
      species, were identified. Downstream of the polyadenylation site in exon 6, a
      dinucleotide repeat sequence was identified. Three putative promoters (P1-P3)
      were localised in the 5' region of the gene. RNase protection analysis revealed
      two active promoters in fetal tissues, P2 and P3, whereas P3 was the only
      promoter active in adult tissues. This represents a transcriptional pattern
      different from that in humans or rodents. A novel structural element, an inverted
      repeat, is predicted in the 3' region of the IGF2 gene. This repeat is conserved
      between species and located in a region which is differentially methylated in the
      human and mouse genes and might therefore be involved in the imprinting
      mechanism. The inverted repeat acquires a stem-loop structure in vitro with a
      hybrid A/B-DNA conformation in the stem area. Both in horse and mouse, a
      methylation-sensitive protein binds this structure with a strong requirement for
      the loop area. Furthermore, the protein might be developmentally regulated.

PMID- 9512530
TI  - Purification, characterization and molecular cloning of TGP1, a novel G-DNA
      binding protein from Tetrahymena thermophila.
AB  - G-DNA, a polymorphic family of four-stranded DNA structures, has been proposed to
      play roles in a variety of biological processes including telomere function,
      meiotic recombination and gene regulation. Here we report the purification and
      cloning of TGP1, a G-DNA specific binding protein from Tetrahymena thermophila.
      TGP1 was purified by three-column chromatographies, including a G-DNA affinity
      column. Two major proteins (approximately 80 and approximately 40 kDa) were
      present in the most highly purified column fraction. Renaturation experiments
      showed that the approximately 80 kDa protein contains TGP1 activity. Biochemical
      characterization showed that TGP1 is a G-DNA specific binding protein with a
      preference for parallel G-DNAs. The TGP1/DNA complex has a dissociation constant
      (Kd) of approximately 2.2 x 10(-8) M and TGP1 can form supershift in gel mobility
      shift assays. The cDNA coding TGP1 was cloned and sequenced based upon an
      internal peptide sequence obtained from the approximately 80 kDa protein.
      Sequence analyses showed that TGP1 is a basic protein with a pI of 10.58, and
      contains two extensively hydrophilic and basic domains. Homology searches
      revealed that TGP1 is a novel protein sharing weak similarities with a number of
      proteins.

PMID- 9512531
TI  - Identification of stress-responsive genes in Caenorhabditis elegans using RT-PCR
      differential display.
AB  - In order to identify genes that are differentially expressed as a consequence of
      oxidative stress due to paraquat we used the differential display technique to
      compare mRNA expression patterns in Caenorhabditis elegans . A C.elegans mixed
      stage worm population and a homogeneous larval population were treated with 100
      mM paraquat, in parallel with controls. Induction of four cDNA fragments,
      designated L-1, M-47, M-96 and M-132, was confirmed by Northern blot analysis
      with RNA from stressed and unstressed worm populations. A 40-fold increase in the
      steady-state mRNA level in the larval population was observed for the L-1/M-47
      gene, which encodes the detoxification enzyme glutathione S-transferase. A
      potential stress-responsive transcription factor (M-132) with C2H2-type zinc
      finger motifs and an N-terminal leucine zipper domain was identified. The M-96
      gene encodes a novel stress-responsive protein. Since paraquat is known to
      generate superoxide radicals in vivo , the response of the C.elegans superoxide
      dismutase (SOD) genes to paraquat was also investigated in this study. The steady
      state mRNA levels of the manganese-type and the copper/zinc-type SODs increased 2
      fold in the larval population in response to paraquat, whereas mixed stage
      populations did not show any apparent increase in the levels of these SOD mRNAs.

PMID- 9512532
TI  - Consensus-degenerate hybrid oligonucleotide primers for amplification of
      distantly related sequences.
AB  - We describe a new primer design strategy for PCR amplification of unknown targets
      that are related to multiply-aligned protein sequences. Each primer consists of a
      short 3' degenerate core region and a longer 5' consensus clamp region. Only 3-4
      highly conserved amino acid residues are necessary for design of the core, which
      is stabilized by the clamp during annealing to template molecules. During later
      rounds of amplification, the non-degenerate clamp permits stable annealing to
      product molecules. We demonstrate the practical utility of this hybrid primer
      method by detection of diverse reverse transcriptase-like genes in a human
      genome, and by detection of C5DNA methyltransferase homologs in various plant
      DNAs. In each case, amplified products were sufficiently pure to be cloned
      without gel fractionation. This COnsensus-DEgenerate Hybrid Oligonucleotide
      Primer (CODEHOP) strategy has been implemented as a computer program that is
      accessible over the World Wide Web (http://blocks.fhcrc.org/codehop.html) and is
      directly linked from the BlockMaker multiple sequence alignment site for hybrid
      primer prediction beginning with a set of related protein sequences.

PMID- 9512533
TI  - The presence of modified nucleotides is required for cloverleaf folding of a
      human mitochondrial tRNA.
AB  - Direct sequencing of human mitochondrial tRNALysshows the absence of editing and
      the occurrence of six modified nucleotides (m1A9, m2G10, Psi27, Psi28 and
      hypermodified nucleotides at positions U34 and A37). This tRNA folds into the
      expected cloverleaf, as confirmed by structural probing with nucleases. The
      solution structure of the corresponding in vitro transcript unexpectedly does not
      fold into a cloverleaf but into an extended bulged hairpin. This non-canonical
      fold, established according to the reactivity to a large set of chemical and
      enzymatic probes, includes a 10 bp aminoacyl acceptor stem (the canonical 7 bp
      and 3 new pairs between residues 8-10 and 65-63), a 13 nt large loop and an
      anticodon-like domain. It is concluded that modified nucleotides have a
      predominant role in canonical folding of human mitochondrial tRNALys.
      Phylogenetic comparisons as well as structural probing of selected in vitro
      transcribed variants argue in favor of a major contribution of m1A9 in this
      process.

PMID- 9512536
TI  - DNA minor groove recognition by a tetrahydropyrimidinium analogue of hoechst
      33258: NMR and molecular dynamics studies of the complex with d(GGTAATTACC)2.
AB  - Hoechst 43254 (H43254), a 2,3,4,5-tetrahydropyrimidin-1-ium analogue of the bis
      benzimidazole minor groove binding agent Hoechst 33258 (H33258), has been studied
      by NMR and restrained molecular dynamics in its complex with d(GGTAATTACC)2. We
      investigate the origin of the enhanced complex stability afforded by the
      replacement of the N-methylpiperazine ring of H33258 with the
      tetrahydropyrimidinium ring of H43254, the latter presenting the opportunity for
      specific minor groove-directed recognition through a pyrimidinium NH. A set of 25
      drug-DNA NOEs define the binding site with some precision and are used as part of
      the structural analysis using restrained molecular dynamics simulations
      considering explicit solvation and the treatment of electrostatic interactions
      using the particle mesh Ewald method within AMBER 4.1. Starting with three
      different initial structures with the drug located at different sites in the
      groove (pairwise RMSD 4.3-12.6 A) we arrive at three very similar structures
      (pairwise RMSD 0.80-1.34 A) representing one converged binding site at the centre
      of the AATT tract. Two of the three structures show the tetrahydropyrimidinium
      ring to be suitably positioned for an -NH to adenine N3 hydrogen bond suggesting
      that electrostatic interactions may play an important role in the enhanced
      affinity as well as imparting additional A-T specificity. The NMR data show that
      the pyrimidinium NH interaction is dynamic since signal averaging from the two
      sides of the ring indicate rapid rotations in the bound form.

PMID- 9512534
TI  - Apolipoprotein B RNA sequence 3' of the mooring sequence and cellular sources of
      auxiliary factors determine the location and extent of promiscuous editing.
AB  - Apolipoprotein B (apoB) RNA editing involves a cytidine to uridine transition at
      nucleotide 6666 (C6666) 5' of an essential cis -acting 11 nucleotide motif known
      as the mooring sequence. APOBEC-1 (apoB editing catalytic sub-unit 1) serves as
      the site-specific cytidine deaminase in the context of a multiprotein assembly,
      the editosome. Experimental over-expression of APOBEC-1 resulted in an increased
      proportion of apoB mRNAs edited at C6666, as well as editing of sites that would
      otherwise not be recognized (promiscuous editing). In the rat hepatoma McArdle
      cell line, these sites occurred predominantly 5' of the mooring sequence on
      either rat or human apoB mRNA expressed from transfected cDNA. In comparison,
      over-expression of APOBEC-1 in HepG2 (HepG2-APOBEC) human hepatoma cells, induced
      promiscuous editing primarily 5' of the mooring sequence, but sites 3' of the
      C6666 were also used more efficiently. The capacity for promiscuous editing was
      common to rat, rabbit and human sources of APOBEC-1. The data suggested that
      differences in the distribution of promiscuous editing sites and in the
      efficiency of their utilization may reflect cell-type-specific differences in
      auxiliary proteins. Deletion of the mooring sequence abolished editing at the
      wild type site and markedly reduced, but did not eliminate, promiscuous editing.
      In contrast, deletion of a pair of tandem UGAU motifs 3' of the mooring sequence
      in human apoB mRNA selectively reduced promiscuous editing, leaving the
      efficiency of editing at the wild type site essentially unaffected. ApoB RNA
      constructs and naturally occurring mRNAs such as NAT-1 (novel APOBEC-1 target-1)
      that lack this downstream element were not promiscuously edited in McArdle or
      HepG2 cells. These findings underscore the importance of RNA sequences and the
      cellular context of auxiliary factors in regulating editing site utilization.

PMID- 9512535
TI  - Isolation of novel human and mouse genes of the recA/RAD51 recombination-repair
      gene family.
AB  - Genes from the recA/RAD51 family play essential roles in homologous recombination
      in all organisms. Using sequence homologies from eukaryotic members of this
      family we have identified fragments of two additional mammalian genes with
      homology to RAD51. Cloning the full-length cDNAs for both human and mouse genes
      showed that the sequences are highly conserved, and that the predicted proteins
      have characteristic features of this gene family. One of the novel genes (R51H2)
      occurs in two forms in human cDNA, differing extensively at the 3' end, probably
      due to an unusual form of alternative splicing. The new genes (R51H2 and R51H3)
      were mapped to human chromosomes 14q23-24 and 17q1.2, respectively. Expression
      studies showed that R51H2 is expressed at lower levels than R51H3 , but that
      expression of both genes occurs at elevated levels in the testis compared with
      other tissues. The combination of gene structure conservation and the transcript
      expression patterns suggests that these new members of the recA/RAD51 family may
      also function in homologous recombination-repair pathways.

PMID- 9512537
TI  - Sequence specific interaction of Mycobacterium smegmatis topoisomerase I with
      duplex DNA.
AB  - We have identified strong topoisomerase sites (STS) for Mycobacteruim smegmatis
      topoisomerase I in double-stranded DNA context using electrophoretic mobility
      shift assay of enzyme-DNA covalent complexes. Mg2+, an essential component for
      DNA relaxation activity of the enzyme, is not required for binding to DNA. The
      enzyme makes single-stranded nicks, with transient covalent interaction at the 5'
      end of the broken DNA strand, a characteristic akin to prokaryotic
      topoisomerases. More importantly, the enzyme binds to duplex DNA having a
      preferred site with high affinity, a property similar to the eukaryotic type I
      topoisomerases. The preferred cleavage site is mapped on a 65 bp duplex DNA and
      found to be CG/TCTT. Thus, the enzyme resembles other prokaryotic type I
      topoisomerases in mechanistics of the reaction, but is similar to eukaryotic
      enzymes in DNA recognition properties.

PMID- 9512538
TI  - Dimerization of the testis brain RNA-binding protein (translin) is mediated
      through its C-terminus and is required for DNA- and RNA-binding.
AB  - Testis brain-RNA-binding protein (TB-RBP) is a single-stranded DNA- and RNA
      binding protein that is involved in chromosomal translocations, mRNA transport
      and translational regulation. Here we show from in vitro and in vivo protein
      binding studies that TB-RBP dimers are the minimum structural unit needed for DNA
      and RNA-binding. Truncation studies demonstrate that the C-terminus of 55 amino
      acids of TB-RBP is essential, but not sufficient for DNA- or RNA-binding, and
      deletion of the leucine zipper motif in the C-terminus abolishes DNA- and RNA
      binding. Changing cysteine 225 in the C-terminus to alanine does not
      significantly reduce DNA- or RNA-binding, but reduces the stability of the dimer.
      We conclude that the leucine zipper motif is required to maintain two molecules
      of TB-RBP as a dimer which is stabilized by a disulfide bond involving cysteine
      225.

PMID- 9512539
TI  - Mutational analysis of p50E4F suggests that DNA binding activity is mediated
      through an alternative structure in a zinc finger domain that is regulated by
      phosphorylation.
AB  - p50E4F is a cellular transcription factor whose DNA binding activity is
      stimulated in a phosphorylation-dependent manner by products of the adenovirus
      E1A oncogene. Although p50E4F does not contain a bZIP DNA binding motif, it binds
      a tandemly repeated palindromic sequence in the adenovirus E4 promoter that is
      recognized by a large number of bZIP proteins, but with much greater stability.
      Analysis of deletions in the p50E4F sequence identified the regions that are
      responsible for its unique DNA binding properties. Sequence-specific DNA binding
      and factor dimerization were localized to a C-terminal region containing two
      C2H2and one CCHC zinc finger motifs; the phosphorylation site critical for DNA
      binding activity was also localized to this domain. The high stability of p50E4F
      binding also required residues within the first 83 amino acids of the N-terminus.
      Analysis of single and double amino acid substitutions in the C-terminal zinc
      finger domain demonstrated that while the second C2H2zinc finger was required for
      DNA binding activity, the putative structures of the first C2H2and the CCHC zinc
      fingers were not. Instead, residues from these other zinc finger motifs appeared
      to participate in an alternative structure that mediates DNA binding activity and
      is regulated by phosphorylation.

PMID- 9512540
TI  - Modelling the secondary structures of slippage-prone hypervariable RNA regions:
      the example of the tiger beetle 18S rRNA variable region V4.
AB  - Variable regions within ribosomal RNAs frequently vary in length as a result of
      incorporating products of slippage. This makes constructing secondary structure
      models problematic because base homology is difficult or impossible to establish
      between species. Here, we model such a region by comparing the results of the
      MFOLD suboptimal folding algorithm for different species to identify conserved
      structures. Based on the reconstruction of base change on a phylogenetic tree of
      the species and comparison against null models of character change, we devise a
      statistical analysis to assess support of these structures from compensatory and
      semi-compensatory (i.e. G.C to G.U or A.U to G.U) mutations. As a model system we
      have used variable region V4 from cicindelid (tiger beetle) small subunit
      ribosomal RNAs (SSU rRNAs). This consists of a mixture of conserved and highly
      variable subregions and has been subject to extensive comparative analysis in the
      past. The model that results is similar to a previously described model of this
      variable region derived from a different set of species and contains a novel
      structure in the central, highly variable part. The method we describe may be
      useful in modelling other RNA regions that are subject to slippage.

PMID- 9512541
TI  - Isolation and characterization of a human cDNA for mRNA 5'-capping enzyme.
AB  - The human mRNA 5'-capping enzyme cDNA was identified. Three highly related cDNAs,
      HCE1 (human mRNAcappingenzyme1), HCE1A and HCE1B , were isolated from a HeLa cDNA
      library. The HCE1 cDNA has the longest ORF, which can encode a 69 kDa protein. A
      short region of 69 bp in the 3'-half of the HCE1 ORF was missing in HCE1A and
      HCE1B , and, additionally, HCE1B has an early translation termination signal,
      which suggests that the latter two cDNAs represent alternatively spliced product.
      When expressed in Escherichia coli as a fusion protein with glutathione S 
      transferase, Hce1p displayed both mRNA 5'-triphosphatase (TPase) and mRNA 5'
      guanylyltransferase (GTase) activities, and it formed a cap structure at the 5'
      triphosphate end of RNA, demonstrating that it indeed specifies an active mRNA 5'
      capping enzyme. The recombinant proteins derived from HCE1A and HCE1B possessed
      only TPase activity. When expressed from ADH1 promoter, HCE1 but not HCE1A and
      HCE1B complemented Saccharomyces cerevisiae CEG1 and CET1 , the genes for GTase
      and TPase, respectively. These results demonstrate that the N-terminal part of
      Hce1p is responsible for TPase activity and the C-terminal part is essential for
      GTase activity. In addition, the human TPase domain cannot functionally
      substitute for the yeast enzyme in vivo.

PMID- 9512542
TI  - Escherichia coli RNA and DNA polymerase bypass of dihydrouracil: mutagenic
      potential via transcription and replication.
AB  - Dihydrouracil (DHU) is a DNA base damage product produced in significant amounts
      by ionizing radiation damage to cytosine under anoxic conditions. DHU represents
      a model for pyrimidine base damage (ring saturation products) of the type
      recognized and repaired by Escherichia coli endonuclease III and its homologs in
      other species. We have built this lesion into synthetic oligonucleotides, with
      DHU placed at a single location downstream from an E.coli RNA polymerase
      promoter. This construct was used to determine the effect of DHU when encountered
      on a DNA template strand by either E.coli RNA or DNA polymerase (Klenow
      fragment). Single round transcription experiments or primer extension-type
      replication experiments were conducted in order to make a direct comparison
      between RNA and DNA polymerases with DHU placed within the same sequence context.
      Both DNA and RNA polymerase efficiently bypass DHU and insert adenine opposite
      this lesion. These results suggest that DHU is mutagenic with respect to both
      replication and transcription and have implications for DNA repair as well the
      routes leading to generation of mutant proteins in dividing and non-dividing
      cells.

PMID- 9512543
TI  - The processivity of DNA synthesis exhibited by drug-resistant variants of human
      immunodeficiency virus type-1 reverse transcriptase.
AB  - The reverse transcriptase (RT) of human immunodeficiency virus (HIV) undergoes
      rapid mutagenesis due to selective pressure by RT inhibitors which renders the
      mutated RT variants resistant to these inhibitors. Resistance to nucleoside
      analogs during drug therapy results from point mutations that lead to specific
      variations in the RT sequences. It was recently shown that several well-defined
      drug-resistant variants of HIV-1 RT (i.e. Leu74Val, Glu89Gly, Tyr183Phe,
      Met184Lue, Met184Val and Met184Ile) show enhanced accuracy of DNA synthesis
      relative to wild-type HIV-1 RT (as evident from a reduction in the capacity to
      introduce mispairs and to elongate them). Since the last two Met184 variants were
      shown also to possess decreased processivity of DNA synthesis, it was recently
      suggested that there might be an inverse correlation between the apparent in
      vitro fidelity and processivity of DNA synthesis in drug-resistant HIV-1 RT
      mutants. In the present study we have conducted a comparative analysis of the
      processivity of DNA synthesis on both DNA and RNA templates of the Leu74Val,
      Glu89Gly, Tyr183Phe and Met184Leu drug-resistant mutants of HIV-1 RT in
      comparison with wild-type RT. Apart from the Met184 mutant, which shows reduced
      relative processivity (similar to the other mutants of residue 184 already
      studied), the other three variants have relative processivity at least as high as
      that of wild-type RT. This suggests that the inverse correlation between reduced
      processivity and increased fidelity is restricted only to mutants with
      modifications of Met184. The results presented may bear on potential mechanistic
      and structural differences in the involvement of the various mutated residues
      studied in processivity, fidelity and sensitivity to nucleoside analogs.

PMID- 9512544
TI  - Baculovirus surface display: construction and screening of a eukaryotic epitope
      library.
AB  - The baculovirus expression system was utilized to serve as a tool for ligand
      selection, demonstrating the applicability of the system to the generation and
      screening of eukaryotic expression libraries. The HIV-1-gp41 epitope 'ELDKWA',
      specific for the neutralizing human mAb 2F5, was inserted into the antigenic site
      B of influenza virus hemagglutinin and expressed on the surface of baculovirus
      infected insect cells. In order to improve the antigenicity of the epitope within
      the hemagglutinin, and therefore enhance the specific binding of 2F5, we inserted
      three additional, random amino acids adjacent to the epitope. This pool of
      hemagglutinin genes was directly cloned into the baculovirus Ac-omega. To
      identify distinct proteins displayed on the cellular surface, we developed a
      screening protocol to select for specific binding capacity of individual viral
      clones. Using fluorescence activated cell sorting (FACS) we isolated a
      baculovirus clone displaying the epitope with markedly increased binding capacity
      out of a pool of 8000 variants in only one sorting step. Binding properties of
      the identified ligand were examined by FACS performing a competition assay.

PMID- 9512546
TI  - Sequence-specific DNA recognition by the myb-like domain of the human telomere
      binding protein TRF1: a model for the protein-DNA complex.
AB  - Telomeres consist of tandem arrays of short G-rich sequence motifs packaged by
      specific DNA binding proteins. In humans the double-stranded telomeric TTAGGG
      repeats are specifically bound by TRF1 and TRF2. Although telomere binding
      proteins from evolutionarily distant species are not sequence homologues, they
      share a Myb-like DNA binding motif. Here we have used gel retardation, primer
      extension and DNase I footprinting analyses to define the binding site of the
      isolated Myb-like domain of TRF1 and present a three-dimensional model for its
      interaction with human telomeric DNA. Our results suggest that the Myb-like
      domain of TRF1 recognizes a binding site centred on the sequence GGGTTA and that
      its DNA binding mode is similar to that of the homeodomain-like motifs of the
      yeast telomere binding protein RAP1. The implications of these findings for
      recognition of telomeric DNA in general are discussed.

PMID- 9512545
TI  - Signal-dependent degradation of IkappaBalpha is mediated by an inducible
      destruction box that can be transferred to NF-kappaB, bcl-3 or p53.
AB  - Activation of the transcription factor NF-kappaB in response to a variety of
      stimuli is governed by the signal-induced proteolytic degradation of NF-kappaB
      inhibitor proteins, the IkappaBs. We have investigated the sequence requirements
      for signal-induced IkappaBalpha phosphorylation and proteolysis by generating
      chimeric proteins containing discrete sub-regions of IkappaBalpha fused to the
      IkappaBalpha homologue Bcl-3, the transcription factor NF-kappaB1/p50 and the
      tumour suppressor protein p53. Using this approach we show that the N-terminal
      signal response domain (SRD) of IkappaBalpha directs their signal-dependent
      phosphorylation and degradation when transferred to heterologous proteins. The C
      terminal PEST sequence from IkappaBalpha was not essential for induced
      proteolysis of the chimeric proteins. A deletion analysis conducted on the SRD
      identified a 25 amino acid sub-domain of IkappaBalpha that is necessary and
      sufficient for the degradative response in vivo and for recognition by TNFalpha
      dependent IkappaBalpha kinase in vitro . The results obtained should prove
      instrumental in the further characterization of IkappaB-specific kinases, as well
      as the E2 and E3 enzymes responsible for IkappaBalpha ubiquitination.
      Furthermore, they suggest a novel strategy for generating conditional mutants, by
      targetting heterologous proteins for transient elimination by the IkappaBalpha
      pathway.

PMID- 9512547
TI  - Non-canonical inteins.
AB  - Previous analyses have shown that inteins (protein splicing elements) employ two
      structural organizations: the 'canonical' Nintein-Dod-inteinC found in dozens of
      inteins and a 'non-canonical' Nintein-inteinC described in two inteins, where
      Nintein at the N-terminus and inteinC at the C-terminus are conserved domains
      involved in self-splicing and Dod is the Dod DNA endonuclease (DNase). In this
      study, four non-canonical inteins, each with unique structural features, have
      been identified using alignment-based Hidden Markov Models. A Nintein-inteinC
      intein, carrying an unprecedented replacement of the N-terminal catalytic
      Cys(Ser) by Ala, is described in a putative ATPase encoded by Methanococcus
      jannaschii . Three replicative proteins of Synechocystis spp. contain inteins
      with the organizations: (i) Nintein minus X minus inteinC over Dod, where X is an
      uncharacterized domain and Dod DNase is located in an alternative open reading
      frame (ORF) being embedded between two novel CG and YK domains; (ii) Nintein-HN
      inteinC, where HN stands for phage-like DNase from the EX1H-HX3H family; (iii)
      Nintein>|<inteinC, where >|< indicates that the intein domains are associated
      with a disrupted host protein encoded by two spatially separated ORFs. The
      expression of some of these newly identified inteins may affect the intein hosts.
      The variety of structural forms of inteins could have evolved through invasion of
      self-splicing proteases by different mobile DNases or the departure of mobile
      DNases from canonical inteins.

PMID- 9512548
TI  - The joining of blunt DNA ends to 3'-protruding single strands in Escherichia
      coli.
AB  - In eukaryotic and prokaryotic organisms DNA double-strand breaks with non
      complementary ends can be joined by mechanisms of illegitimate recombination. We
      examined the joining of 3'-protruding single strand (PSS) ends, which do not have
      recessed 3' hydroxyls that can allow for fill-in DNA synthesis, to blunt ends.
      End-joining was examined by electro-transforming Escherichia coli strains with
      linearized plasmid DNA, sequencing the resulting junctions, and determining the
      transformation frequencies. Three different E.coli strains were examined: MC1061,
      which has no known recombination or DNA repair defects, HB101 (rec A-) and SURE
      (recB- recJ-). No striking differences were found in either the spectrum of
      products observed or the efficiency of end-joining between these strains. As in
      vertebrate systems, the majority of the products were overlaps between directly
      repeated DNA sequences. 3'-PSS are frequently preserved in vertebrate systems,
      but they were not preserved in our experiments unless the transforming DNA was
      pretreated with a DNA polymerase.

PMID- 9512549
TI  - An RNA aptamer to the xanthine/guanine base with a distinctive mode of purine
      recognition.
AB  - RNAs that bind to xanthine (2,6-dioxypurine) were isolated from a population of
      10(12) random sequences by in vitro selection. These xanthine-binding RNAs were
      found to have a 10 nt consensus sequence at an internal loop in the most probable
      secondary structure. By trimming one of the xanthine-binding RNAs, a
      representative xanthine-binding RNA (designated as XBA) of 32 nt residues was
      prepared. The dissociation constant of this RNA for xanthine was determined to be
      3.3 microM by equilibrium filtration experiments. The XBA RNA can bind to guanine
      as well, whereas it hardly accommodates adenine, cytosine or uracil. The K d
      values for various xanthine/guanine analogues were determined, and revealed that
      the N1H, N7 and O6 moieties of the ligand are involved in the binding with the
      XBA RNA. The ribonuclease sensitivities of some internal-loop residues changed
      upon the addition of xanthine, suggesting that the internal loop of the XBA RNA
      is involved in the ligand binding. Interestingly, the consensus sequence of the
      xanthine/guanine-binding RNAs is the same as a sequence in one of the internal
      loops of the hairpin ribozyme, except for a substitution that is neutral with
      respect to xanthine/guanine binding.

PMID- 9512550
TI  - E1A represses apolipoprotein AI enhancer activity in liver cells through a pRb-
      and CBP-independent pathway.
AB  - The apolipoprotein AI (apoAI) promoter/enhancer contains multiple cis -acting
      elements on which a variety of hepatocyte-enriched and ubiquitous transcription
      factors function synergistically to regulate liver-specific transcription.
      Adenovirus E1A proteins repress tissue-specific gene expression and disrupt the
      differentiated state in a variety of cell types. In this study expression of E1A
      12Sor 13S in hepatoblastoma HepG2 cells repressed apoAI enhancer activity 8-fold.
      Deletion mapping analysis showed that inhibition by E1A was mediated by the apoAI
      promoter site B. E1A selectively inhibited the ability of HNF3beta and HNF3alpha
      to transactivate reporter genes controlled by the apoAI site B and the HNF3
      binding site from the transthyretin promoter. The E1A-mediated repression of HNF3
      activity was not reversed by overexpression of HNF3beta nor did E1A alter nuclear
      HNF3beta protein levels or inhibit HNF3 binding to DNA in mobility shift assays.
      Overexpression of two cofactors known to interact with E1A, pRb and CBP failed to
      overcome inhibition of HNF3 activity. Similarly, mutations in E1A that disrupt
      its interaction with pRb or CBP did not compromise its ability to repress
      HNF3beta transcriptional activity. These data suggest that E1A inhibits HNF3
      activity by inactivating a limiting cofactor(s) distinct from pRb or CBP.

PMID- 9512551
TI  - Specific tandem GG to TT base substitutions induced by acetaldehyde are due to
      intra-strand crosslinks between adjacent guanine bases.
AB  - Acetaldehyde is present in tobacco smoke and automotive exhaust gases, is
      produced by the oxidation of ethanol, and causes respiratory organ cancers in
      animals. We show both the types and spectra of acetaldehyde-induced mutations in
      supF genes in double- and single-stranded shuttle vector plasmids replicated in
      human cells. Of the 101 mutants obtained from the double-stranded plasmids, 63%
      had tandem base substitutions, of which the predominant type is GG to TT
      transversions. Of the 44 mutants obtained from the single-stranded plasmids, 39%
      had tandem mutations that are of a different type than the double-stranded ones.
      The GG to TT tandem substitutions could arise from intra-strand crosslinks. Our
      data indicate that acetaldehyde forms intra- as well as inter-strand crosslinks
      between adjacent two-guanine bases. Based upon the following observations: XP-A
      protein binds to acetaldehyde-treated DNA, DNA excision repair-deficient
      xeroderma pigmentosum (XP) cells were more sensitive to acetaldehyde than the
      repair-proficient normal cells, and a higher frequency of acetaldehyde-induced
      mutations of the shuttle vectors was found in XP cells than in normal cells, we
      propose that the DNA damage caused by acetaldehyde is removed by the nucleotide
      excision repair pathway. Since treatment with acetaldehyde yields very specific
      GG to TT tandem base substitutions in DNA, such changes can be used as a probe to
      identify acetaldehyde as the causal agent in human tumors.

PMID- 9512552
TI  - Characterization of a novel trypanosomatid small nucleolar RNA.
AB  - Trypanosomes possess unique RNA processing mechanisms including trans- splicing
      of pre-mRNA and RNA editing of mitochondrial transcripts. The previous finding of
      a trimethylguanosine (TMG) capped U3 homologue in trypanosomes suggests that rRNA
      processing may be related to the processing in other eukaryotes. In this study,
      we describe the first trypanosomatid snoRNA that belongs to the snoRNAs that were
      shown to guide ribose methylation of rRNA. The RNA, identified in the monogenetic
      trypanosomatid Leptomonas collosoma, was termed snoRNA-2 and is encoded by a
      multi-copy gene. SnoRNA-2 is 85 nt long, it lacks a 5' cap and possesses the C
      and D boxes characteristic to all snoRNAs that bind fibrillarin. Computer
      analysis indicates a potential for base-pairing between snoRNA-2 and 5.8S rRNA,
      and 18S rRNA. The putative interaction domains obey the rules suggested for the
      interaction of guide snoRNA with its rRNA target for directing ribose methylation
      on the rRNA. However, mapping the methylated sites on the 5.8S rRNA and 18S rRNA
      indicates that the expected site on the 5.8S is methylated, whereas the site on
      the 18S is not. The proposed interaction with 5.8S rRNA is further supported by
      the presence of psoralen cross-link sites on snoRNA-2. GenBank search suggests
      that snoRNA-2 is not related to any published snoRNAs. Because of the early
      divergence of the Trypanosomatidae from the eukaryotic lineage, the presence of a
      methylating snoRNA that is encoded by a multi-copy gene suggests that methylating
      snoRNAs may have evolved in evolution from self-transcribed genes.

PMID- 9512553
TI  - Overlapping RNA and DNA binding domains of the wt1 tumor suppressor gene product.
AB  - The Wilms' tumour suppressor gene (wt1) is mutated in a subset of patients with
      Wilms' tumour and has a critical role in urogenital development. wt1 encodes a
      zinc finger transcription factor which regulates expression of several genes
      involved in cellular proliferation and differentiation. Although a number of
      studies have characterized the DNA binding properties of the WT1 protein, recent
      evidence has suggested that WT1 may also have a role in RNA metabolism. We have
      used an RNA selection method to identify WT1 binding ligands from a random RNA
      pool. Three groups of RNA ligands specifically recognized by WT1 were identified.
      Mutational analysis pinpointed ribonucleotide sequences critical for binding.
      Analysis of truncated WT1 proteins demonstrated that three of four zinc fingers
      were necessary for RNA-protein interaction. The naturally occurring WT1 isoforms
      with insertion of lysine, threonine and serine between zinc fingers three and
      four were unable to bind the selected RNAs. The selected RNA ligands competed
      with the cognate WT1 DNA binding site for complex formation with WT1. Our
      findings suggest potential cellular RNA target sequences for WT1 and provide
      tools for studying the structural and functional properties of this tumour
      suppressor protein.

PMID- 9512554
TI  - Cruciform-extruding regulatory element controls cell-specific activity of the
      tyrosine hydroxylase gene promoter.
AB  - Tyrosine hydroxylase (TH) is expressed specifically in catecholaminergic cells.
      We have identified a novel regulatory sequence in the upstream region of the
      bovine TH gene promoter formed by a dyad symmetry element (DSE1;-352/-307 bp).
      DSE1 supports TH promoter activity in TH-expressing bovine adrenal medulla
      chromaffin (BAMC) cells and inhibits promoter activity in non-expressing TE671
      cells. DNase I footprinting of relaxed TH promoter DNA showed weak binding of
      nuclear BAMC cell proteins to a short sequence in the right DSE1 arm. In BAMC
      cells, deletion of the right arm markedly reduced the expression of luciferase
      from the TH promoter. However, deletion of the left DSE1 arm or its reversed
      orientation (RevL) also inactivated the TH promoter. In supercoiled TH promoter,
      DSE1 assumes a cruciform-like conformation i.e., it binds cruciform-specific 2D3
      antibody, and S1 nuclease-cleavage and OsO4-modification assays have identified
      an imperfect cruciform extruded by the DSE1. DNase I footprinting of supercoiled
      plasmid showed that cruciformed DSE1 is targeted by nuclear proteins more
      efficiently than the linear duplex isomer and that the protected site encompasses
      the left arm and center of DSE1. Our results suggest that the disruption of
      intrastrand base-pairing preventing cruciform formation and protein binding to
      DSE1 is responsible for its inactivation in DSE1 mutants. DSE1 cruciform may act
      as a target site for activator (BAMC cells) and repressor (TE671) proteins. Its
      extrusion emerges as a novel mechanism that controls cell-specific promoter
      activity.

PMID- 9512555
TI  - Correct usage of multiple transcription initiation sites and C/EBP-dependent
      transcription activation of the rat XDH/XO TATA-less promoter requires downstream
      elements located in the coding region of the gene.
AB  - In the present study, we have shown that a downstream element located in the
      coding region of the TATA-less rat xanthine dehydrogenase/oxidase (XDH/XO) gene (
      7 to +42) plays an important role in transcription initiation and C/EBP
      transcriptional activation. Previous work from our laboratory has shown that the
      promoter is organized with multiple initiator elements (Inr 1, 2, 3 and 4) which
      are important for transcription initiation. Additionally, we had identified two
      C/EBP binding sites upstream of this promoter. Deletional and mutational studies
      revealed that C/EBP binding was not essential for the basal level of
      transcriptional initation. However when XO-luciferase constructs include
      downstream sequence extending to +42 there is development of C/EBP sensitivity as
      well as a shift in the initiator usage. In the absence of the downstream element,
      primer extension analyses reveals Inr 3 and 4 to be the major start sites but in
      the presence of this additional sequence the usage is shifted to Inr 1 and 2.
      This shift in Inr usage more closely resembles that seen in intact macrophages or
      liver cells. Gel mobility shift assays indicate the presence of several binding
      factors located in this downstream region, one of which has been identified as YY
      1. We postulate that YY-1 allows DNA bending which permits the upstream C/EBP
      elements to exhibit a transcriptional activation which is not seen when the
      downstream element is absent. This study presents a potential model for
      regulation of the XDH/XO promoter.

PMID- 9512556
TI  - Terminal transferase-dependent PCR: a versatile and sensitive method for in vivo
      footprinting and detection of DNA adducts.
AB  - We report here a new, sensitive and versatile genomic sequencing method, which
      can be used for in vivo footprinting and studies of DNA adducts. Starting with
      mammalian genomic DNA, single-stranded products are made by repeated primer
      extension; these products are subjected to homopolymeric ribonucleotide tailing
      at the 3' termini with terminal deoxynucleotidyl transferase and then ligated to
      a double-stranded linker having a complementary 3' overhang, and used for PCR.
      This terminal transferase-dependent PCR (TDPCR) method can generate band signals
      many-fold stronger than conventional ligation-mediated PCR (LMPCR). A UV
      photofootprint in the mouse Xist gene promoter can be easily detected using
      TDPCR. No special enzymes or chemical reagents are needed to convert DNA adducts
      into strand breaks. Any lesion that blocks primer extension should be detectable.

PMID- 9512557
TI  - Positional cloning without a genome map: using 'Targeted RFLP Subtraction' to
      isolate dense markers tightly linked to the regA locus of Volvox carteri.
AB  - The ability to isolate genes defined by mutant phenotypes has fueled the rapid
      progress in understanding basic biological mechanisms and the causes of inherited
      diseases. Positional cloning, a commonly used method for isolating genes
      corresponding to mutations, is most efficiently applied to the small number of
      model organisms for which high resolution genetic maps exist. We demonstrate a
      new and generally applicable positional cloning method that obviates the need for
      a genetic map. The technique is based on Restriction Fragment Length Polymorphism
      (RFLP) Subtraction, a method that isolates RFLP markers spanning an entire
      genome. The new method, Targeted RFLP Subtraction (TRS), isolates markers from a
      specific region by combining RFLP Subtraction with a phenotypic pooling strategy.
      We used TRS to directly isolate dense markers tightly linked to the regA gene of
      the eukaryotic green alga Volvox. As a generally applicable method for saturating
      a small targeted region with DNA markers, TRS should facilitate gene isolation
      from diverse organisms and accelerate the process of physically mapping specific
      regions in preparation for sequence analysis.

PMID- 9512558
TI  - Stimulation and suppression of PCR-mediated recombination.
AB  - Recombination, or chimera formation, is known to occur between related template
      sequences present in a single PCR amplification. To characterize the conditions
      under which such recombinant amplification products form we monitored the
      exchange of sequence between two homologous templates carrying different
      restriction sites separated by 282 bp. Using a typical cycling program the rates
      of recombination between the two restriction sites were 1 and 7% using Taq and
      Vent polymerases respectively over 12 doublings. However, by using long
      elongation times and cycling only to the mid-point of the amplification
      recombination could be suppressed below visual detection with both polymerases.
      Conversely, cycling programs designed to promote incomplete primer elongation and
      subsequent template strand exchange stimulated recombination to >20%.

PMID- 9512559
TI  - Position-independent expression of a human nerve growth factor-luciferase
      reporter gene cloned on a yeast artificial chromosome vector.
AB  - Two yeast artificial chromosomes containing the entire human nerve growth factor
      gene were isolated and mapped. By homologous recombination a luciferase gene was
      precisely engineered into the coding portion of the NGF gene and a neomycin
      selection marker was placed adjacent to one of the YAC telomeres. Expression of
      the YAC-based NGF reporter gene and a plasmid-based NGF reporter gene were
      compared with the regulation of endogenous mouse NGF protein in mouse L929
      fibroblasts. In contrast to the plasmid-based reporter gene, expression and
      regulation of the YAC-based reporter gene was independent of the site of
      integration of the transgene. Basic fibroblast growth factor and okadaic acid
      stimulated expression of the YAC transgene, whereas transforming growth factor
      beta and dexamethasone inhibited it. Although cyclic AMP strongly stimulated
      production of the endogenous mouse NGF, no effect was seen on the human NGF
      reporter genes. Downregulation of the secretion of endogenous mouse NGF already
      occurred at an EC50 of 1-2 nM dexamethasone, but downregulation of the expression
      of NGF reporter genes occurred only at EC50 of 10 nM. This higher concentration
      was also required for upregulation of luciferase genes driven by the
      dexamethasone-inducible promoter of the mouse mammary tumor virus in L929
      fibroblasts.

PMID- 9512560
TI  - A common 40 amino acid motif in eukaryotic RNases H1 and caulimovirus ORF VI
      proteins binds to duplex RNAs.
AB  - Eukaryotic RNases H from Saccharomyces cerevisiae , Schizosaccharomyces pombe and
      Crithidia fasciculata , unlike the related Escherichia coli RNase HI, contain a
      non-RNase H domain with a common motif. Previously we showed that S.cerevisiae
      RNase H1 binds to duplex RNAs (either RNA-DNA hybrids or double-stranded RNA)
      through a region related to the double-stranded RNA binding motif. A very similar
      amino acid sequence is present in caulimovirus ORF VI proteins. The hallmark of
      the RNase H/caulimovirus nucleic acid binding motif is a stretch of 40 amino
      acids with 11 highly conserved residues, seven of which are aromatic. Point
      mutations, insertions and deletions indicated that integrity of the motif is
      important for binding. However, additional amino acids are required because a
      minimal peptide containing the motif was disordered in solution and failed to
      bind to duplex RNAs, whereas a longer protein bound well. Schizosaccharomyces
      pombe RNase H1 also bound to duplex RNAs, as did proteins in which the
      S.cerevisiae RNase H1 binding motif was replaced by either the C.fasciculata or
      by the cauliflower mosaic virus ORF VI sequence. The similarity between the RNase
      H and the caulimovirus domain suggest a common interaction with duplex RNAs of
      these two different groups of proteins.

PMID- 9512562
TI  - An improved PCR-mutagenesis strategy for two-site mutagenesis or sequence
      swapping between related genes.
AB  - The QuikChangeTM protocol is one of the simplest and fastest methods for site
      directed mutagenesis, but introduces mutations at only one site at a time, and
      requires two HPLC-purified complementary oligonucleotides. Here, we describe that
      this method can be used with non-overlapping oligonucleotides. By doing this, two
      separate sites can be mutagenised simultaneously, or money can be saved by using
      a second 'standard' oligonucleotide. By a further modification, we have also used
      the QuikChangeTM approach to exchange DNA sequences between closely related
      genes.

PMID- 9512563
TI  - Intramolecular derivatization of 2'-amino-pyrimidine modified RNA with functional
      groups that is compatible with re-amplification.
AB  - To expand the scope of nucleic acid aptamers as a tool for precise molecular
      recognition, functional groups that are not naturally present in nucleic acid
      molecules are desired. For in vitro selection these new functional groups must be
      compatible with the selection process. The present method allows the introduction
      of succinimide activated side chains at internal amino groups of 2'-amino
      pyrimidine-RNA in a combinatorial fashion that is compatible with enzymatic re
      amplification.

PMID- 9512561
TI  - Interaction between the N-terminus of human topoisomerase I and SV40 large T
      antigen.
AB  - We have attempted to identify human topoisomerase I-binding proteins in order to
      gain information regarding the cellular roles of this protein and the cytotoxic
      mechanisms of the anticancer drug camptothecin, which specifically targets
      topoisomerase I. In the course of this work we identified an interaction between
      the N-terminus of human topoisomerase I and the SV40 T antigen that is detectable
      in vitro using both affinity chromatography and co-immunoprecipitation.
      Additional results indicate that this interaction does not require intermediary
      DNA or stoichiometric quantities of other proteins. Furthermore, the interaction
      is detectable in vivo using a yeast two-hybrid assay. Two binding sites for T
      antigen are apparent on the topoisomerase I protein: one consisting of amino
      acids 1-139, the other present in the 383-765 region of the protein.
      Interestingly, nucleolin, which binds the 166-210 region of topoisomerase I, is
      able to bind an N-terminal fragment of topoisomerase I concurrently with T
      antigen. Taken together with our prior identification of nucleolin as a
      topoisomerase I-binding protein, the current results suggest that helicase
      binding is a major role of the N-terminus of human topoisomerase I and that the
      resultant helicase-topoisomerase complex may function as a eukaryotic gyrase.

PMID- 9512565
TI  - Pay: nurses feel the squeeze.

PMID- 9512564
TI  - Inosine 5'-triphosphate can dramatically increase the yield of NASBA products
      targeting GC-rich and intramolecular base-paired viroid RNA.
AB  - Nucleic acid sequence-based amplification (NASBA) according to the standard
      protocol failed to amplify cRNA of viroids, probably because of their GC-rich and
      intramolecular base-paired structure. However, NASBA in the presence of inosine
      5'-triphosphate successfully amplified the cRNAs to viroids in total nucleic acid
      extracts from citrus plants. As sequence specificity of the cRNA to viroids was
      confirmed by northern analysis, the amplification and fidelity of cRNAs are
      sufficient for the sensitive and specific detection of viroids.

PMID- 9512566
TI  - Labour is accused of failing first real test.

PMID- 9512567
TI  - Divided we fail.

PMID- 9512568
TI  - An achievable goal.

PMID- 9512569
TI  - Spinning a yarn over pay.

PMID- 9512570
TI  - Overcoming tribalism.

PMID- 9512571
TI  - A regulated workforce?

PMID- 9512572
TI  - Clinical decisions: defining meaning through focus groups.
AB  - In this article, the author illustrates the use of an adapted focus group
      process. He uses the example of canvassing the views of registered mental health
      nurses about the meaning of the term clinical decision. The article centres on
      the process involved in what the author has called 'the grounded focus group', a
      combination of traditional focus group work with analysis techniques drawn from
      grounded theory. The author describes the techniques involved, and offers a
      practical guide to the application of such groups, discussing the skills and
      important concerns involved in facilitating focus groups of this type.

PMID- 9512573
TI  - Teamworking in primary care.
AB  - Teamwork in primary care will become increasingly important as the White Paper A
      New NHS is implemented. In this article, the author describes the proceedings of
      a conference held to discuss the implications of this policy.

PMID- 9512574
TI  - Hospital at home: the Bromsgrove experience.
AB  - The aim of this article is to share good practice with interested professionals
      contemplating setting up a hospital at home scheme. The authors present an
      overview of the relevant research literature and describe their own experiences
      of developing the scheme in Bromsgrove.

PMID- 9512575
TI  - Competency-based learning for the surgical assistant.
AB  - In the first of two articles about the benefits and drawbacks of occupational
      standards, the authors describe a competency-based programme of continuing
      education for surgical assistants. The structure and content of the modules
      offered are discussed and the authors emphasise the validation of the courses by
      institutions of higher education. Next week's article will examine occupational
      standards in relation to professional development.

PMID- 9512576
TI  - Controlling body temperature in adults.

PMID- 9512577
TI  - Poor weather also leads to increased pressure on emergency services.

PMID- 9512578
TI  - No place like home.

PMID- 9512579
TI  - Betrayal by the back door.

PMID- 9512580
TI  - Demanding times.

PMID- 9512581
TI  - Local teams to take the lead.

PMID- 9512582
TI  - Making pain a thing of the past.

PMID- 9512583
TI  - At the heart of the NHS.

PMID- 9512584
TI  - The state of emergency.

PMID- 9512586
TI  - Public health on agenda.

PMID- 9512585
TI  - Coping with winter emergencies. Cold comfort.

PMID- 9512587
TI  - Gathering the evidence.

PMID- 9512588
TI  - Sharing the challenge.

PMID- 9512590
TI  - The unique function of the nurse.
AB  - This year's 21st quadrennial congress of the International Council of Nurses
      (ICN) was marked by Professor Dame June Clark's Inaugural Henderson Memorial
      Lecture. In the first of our series of extracts from ICN congress papers, we
      present this shortened version of her lecture.

PMID- 9512589
TI  - Perceptions of the psychiatric nurse's role: a pilot study.
AB  - In this article, the authors report on a face-to-face survey of members of the
      public regarding the role of psychiatric nurses. One open-ended question was
      asked of 100 pedestrians in a city centre. The resulting data were analysed and
      then validated by a panel of senior psychiatric nurses. The researchers found a
      generally positive perception of the role, certainly in relation to the esteem in
      which nurses continue to be held, but detected that the stigma of mental illness
      still surrounds those who have to come in contact with mental health
      professionals. The researchers believe mental health nurses must be better
      prepared to articulate their contribution to mental health care to counteract
      public fear, and that the media can play an important role in this process.

PMID- 9512591
TI  - Using training needs analysis to implement change.
AB  - This article describes the application of a systematic approach to training needs
      analysis prior to a major change in practice. The authors suggest that such a
      systematic approach is a central component in the successful management of
      change.

PMID- 9512592
TI  - Multiple sclerosis.

PMID- 9512593
TI  - [Ultimate responsibility in nursing management].

PMID- 9512594
TI  - [History of nursing--an argument for the autonomy of the nursing profession].

PMID- 9512595
TI  - [What do we mean by evidence? Implications for primary health care nursing. Short
      version of a paper given by professor Sally Kendall at the 2. International
      Congress for Community Health Nursing Research].

PMID- 9512596
TI  - [Communication and language are important elements in nursing].

PMID- 9512597
TI  - [Austrian Nursing Society Salzburg: notification of abuses in homes for the
      aged].

PMID- 9512598
TI  - [Communication within the nursing team. Discussion, promotional talks,
      criticism].

PMID- 9512599
TI  - [The right tone--at the right time--in the right place. Communication from the
      viewpoint of a nurses' aide].

PMID- 9512600
TI  - [Problem-oriented learning and its importance for the improvement of
      communication].

PMID- 9512602
TI  - [Gaiety and lightness in all units: about the Red Nose Clown Doctors].

PMID- 9512601
TI  - [Psychiatry across the border].

PMID- 9512603
TI  - [Preoperative nursing visit. This initiative was started with the motto "Emerging
      from anonymity"].

PMID- 9512604
TI  - [Series: ICN resolutions].

PMID- 9512605
TI  - [Outpatient oncologic nursing service].

PMID- 9512606
TI  - [Austrian Nursing Society, Salzburg: reactions to the denunciation].

PMID- 9512607
TI  - [Kinesthetics in nursing].

PMID- 9512608
TI  - [Children and nursing].

PMID- 9512609
TI  - [Communication between patients' parents and nursing personnel: potentials and
      limits].

PMID- 9512610
TI  - [Care of children with cancer].

PMID- 9512611
TI  - [Practical introduction of the Dorothea Orem nursing model].

PMID- 9512612
TI  - [Why I want to be a pediatric nurse].

PMID- 9512613
TI  - [Prevention of decubitus ulcers in the operating room].

PMID- 9512614
TI  - [Theories, models concepts in nursing or the Babylonian confusion of languages].

PMID- 9512615
TI  - [Development of nursing concepts and nursing processes in practice].

PMID- 9512616
TI  - [Recycling of anti-thrombosis stockings].

PMID- 9512617
TI  - [Terminating work relationships].

PMID- 9512618
TI  - ["Always those ambulance drivers..."].

PMID- 9512619
TI  - ["Social marketing" is no longer a concept but an awareness].

PMID- 9512620
TI  - [Nursing in Slovakia--report of experiences].

PMID- 9512621
TI  - [Farewell to the Essen Education Center].

PMID- 9512622
TI  - [Variable quality in nursing homes].

PMID- 9512623
TI  - [Greater efficiency at any price?].

PMID- 9512624
TI  - [What does food allergy/intolerance mean for MS?].

PMID- 9512625
TI  - [Relatives as a resource?].

PMID- 9512626
TI  - [Medical equipment--new equipment straight from storeroom?. Interview by Arne
      Kjelle Bakke].

PMID- 9512627
TI  - [Vasteralen--job rotation against flight of nurses].

PMID- 9512628
TI  - [Fever rhapsodies].

PMID- 9512629
TI  - [Crib death--death is the only symptom. Interview by Kari Anne Aase].

PMID- 9512630
TI  - [Personnel crisis--unhappy nurses of Akershus Central Hospital. Interview by
      Marit Fonn].

PMID- 9512631
TI  - [Epilepsy/diabetes--the young ones live well, the older ones have trouble.
      Interview by Marit Fonn].

PMID- 9512632
TI  - [I won't forget those tuberculosis children. Interview by Oddrunn Marie Dyrdal].

PMID- 9512633
TI  - [My workplace: Oslo Health Organization Rheumatism Hospital--connecting link.
      Interview by Marit Fonn].

PMID- 9512634
TI  - [From bygone days--the nursing system in the country].

PMID- 9512635
TI  - [Clinical nursing--nurses should be able to mark the abdomen for stomas.
      Interview by Kjell Arne Bakke].

PMID- 9512636
TI  - [Nursing homes in education. Interview by Kari Anne Aase].

PMID- 9512637
TI  - [Oslo psychiatry--the ring is closed for Dikemark. Interview by Kari Anne Aase].

PMID- 9512638
TI  - [Psychiatric services--between institution and outpatient clinic. Interview by
      Erik Harstad].

PMID- 9512639
TI  - [Difficult to manage drug handling].

PMID- 9512641
TI  - [Education--expectations and reality].

PMID- 9512640
TI  - [Special nurses form their own forum].

PMID- 9512642
TI  - [Education--a living textbook].

PMID- 9512643
TI  - [Russian nurses neglect own health].

PMID- 9512644
TI  - [Care groups--makes caring easier to bear].

PMID- 9512645
TI  - Increased mRNA expression of phospholipase D (PLD) isozymes during granulocytic
      differentiation of HL60 cells.
AB  - In response to dibutyryl cyclic AMP (dbcAMP) and all-trans retinoic acid (ATRA),
      HL60 cells differentiate into granulocyte-like cells. Membrane-associated
      phospholipase D (PLD) activity in response to guanosine 5'-O-(3-thiotriphosphate)
      (GTP gamma S) or phorbol myristate acetate (PMA) was upregulated by these
      treatments. Reverse transcriptase-polymerase chain reaction (RT-PCR) analyses
      revealed that both hPLD1a and hPLD1b mRNAs were expressed in HL60 cells and that
      their expression levels increased during differentiation. hPLD2 mRNA levels rose
      dramatically during differentiation. These results suggest that the PLD genes
      undergo changes in transcriptional regulation during granulocytic differentiation
      of HL60 cells.

PMID- 9512646
TI  - Molecular cloning of rat uncoupling protein 2 cDNA and its expression in
      genetically obese Zucker fatty (fa/fa) rats.
AB  - We isolated rat UCP2 cDNA, which has been proposed to play an important role in
      mammalian thermogenesis and body weight regulation. The nucleotide sequence of
      the cDNA revealed that the rat UCP2 protein is composed of 309 amino acid
      residues, and is 99% and 95% identical to the mouse and human proteins,
      respectively. The molecular weight of rat UCP2, calculated from the predicted
      amino acid sequence, was 33,369, and the UCP2 protein of this size was detected
      when the cDNA was expressed in vitro. Northern blot analysis revealed that the
      corresponding mRNA is approximately 1.7 kb in size, and is expressed in a variety
      of rat organs, with predominant expression in the heart, lung and spleen. UCP2
      mRNA levels in the heart, liver, muscle and epididymal adipose tissue of Zucker
      fatty (fa/fa) rats were comparable to those in the lean littermates, while ob
      mRNA level markedly increased in the epididymal adipose tissue of Zucker (fa/fa)
      rats.

PMID- 9512647
TI  - Characteristics of leukotriene biosynthesis by human granulocytes in presence of
      plasma.
AB  - The formation of leukotriene B4 (LTB4) by neutrophils stimulated with the
      ionophore A23187 or physiological stimuli in heparinized plasma was investigated.
      In comparison with neutrophils stimulated (A23187) in a protein-free buffered
      salt solution, neutrophils stimulated in plasma produced only trace amounts of
      LTB4. The addition of human recombinant LTA4-hydrolase or erythrocytes to plasma
      prior to A23187 stimulation strongly and selectively stimulated (> 4-fold) the
      formation of LTB4 supporting that neutrophils activated in plasma with A23187
      release in the extracellular milieu most of LTA4 formed by the cells, and
      indicating that plasma proteins drastically slow down the further metabolism of
      LTA4 released by neutrophils. The formation of LTB4 was then investigated in GM
      CSF-primed neutrophils stimulated with fMLP in plasma; levels of synthesis were
      very low and the addition of erythrocytes prior to stimulation strongly enhanced
      LTB4 synthesis, demonstrating that agonist-stimulated neutrophils also release
      most of LTA4 generated in the extracellular milieu. Investigations on the fate of
      LTA4 in plasma revealed that LTA4 was slowly degraded through an unknown process,
      i.e. not through the previously described non-enzymic hydrolysis resulting in the
      formation of dihydroxy derivatives of LTA4. Using neutrophils labeled with
      tritiated arachidonate, we also demonstrated that neutrophils stimulated in
      plasma with fMLP or A23187, almost exclusively use endogenous arachidonate, as
      opposed to plasma arachidonate, to generate 5-lipoxygenase products. Finally,
      experiments performed with purified eosinophils indicated that contrary to
      neutrophils, the eosinophils do not release LTA4, but directly release LTC4.

PMID- 9512648
TI  - Age-related changes in the activation of aortic cholesteryl ester hydrolases by
      protein kinases in rats.
AB  - Age-related changes in the activities of acid and neutral cholesteryl ester
      hydrolases (ACEH and NCEH) and their activation by protein kinase A (PKA) and
      also by protein kinase C (PKC) were examined in the aortae of 4-, 8-, 12- and 20
      week-old rats in relation to their aortic lipid and lipid peroxides and lipid
      contents. The physiological basal activity as well as total activities of the
      ACEH and NCEH activated by the two kinases, which were high in the aortae of the
      4- and 8-week-old rats, decreased gradually with increasing age to about 40%
      (ACEH) and 50% (NCEH) by 20 weeks of age. The vitamin E intake and ad libitum
      diet intake of the rats each modified the age-related decline of CEH activities.
      The aortic PKA and PKC activities were reflected by the CEH activities to some
      degree. The in vitro exposure of the aortic CEH to active oxygen (AO) generators
      revealed the PKC-mediated activation of CEH, which was inhibited by superoxide
      dismutase and catalase. These results suggested that the activities of ACEH and
      NCEH and their regulatory enzymes may be modulated by the dual effect of
      endogenous AO; an activation of CEH at low doses and an inactivation at high
      doses, or upon a long-term exposure in aging to a low level of endogenous AO.

PMID- 9512649
TI  - Cyclosporin A inhibits oxidant and calcium stimulated phospholipase D activity in
      the rat intestinal mitochondria.
AB  - Mitochondrial swelling and calcium cycling occurs during oxidative stress and can
      be prevented by cyclosporin A (CysA). Our earlier work has shown that enterocyte
      mitochondria contains a phospholipase D (PLD) which can be activated by
      superoxide or calcium. In this study, we have shown that enterocyte mitochondrial
      PLD activated by these agents can be inhibited by cyclosporin A. This was clearly
      shown by the absence of phosphatidic acid (PA) formation and
      phosphatidylethanolamine (PE) degradation. Since this PLD specifically utilizes
      PE as substrate, PLD activity was also assessed by ethanolamine formation which
      was inhibited by CysA. CysA also inhibited the cabbage PLD activity as judged by
      phosphatidylethanol formation. These results suggest that cyclosporin A is an
      inhibitor of PLD and this may be one of the mechanism by which CysA protects
      enterocyte mitochondria from oxidative stress.

PMID- 9512651
TI  - Phospholipid signalling in plants.

PMID- 9512650
TI  - Hepatic responses to inhibition of 3-hydroxy-3-methylglutaryl-CoA reductase: a
      comparison of atorvastatin and simvastatin.
AB  - We have compared the cellular responses to simvastatin (Simva) and atorvastatin
      (Atorva), two potent HMG-CoA reductase inhibitors. The two drugs exhibited
      similar IC50's for inhibition of either rat or human reductase, and single oral
      dosing in rats showed the compounds to be nearly equipotent at inhibiting hepatic
      cholesterol synthesis. Treatment of rats with Simva or Atorva in the feed for
      four days yielded comparable inductions of hepatic reductase activity and
      reductase protein. For example, 0.05% Simva induced reductase activity 27.3 +/-
      9.1 fold and 0.05% Atorva induced activity 26.9 +/- 4.7 fold. This adaptive
      response was also studied in HepG2 cells, a human hepatoblastoma line, cultured
      for 24 h in delipidated serum and then for an additional 24 h with Simva or
      Atorva. Over a broad range (10 nM-10 microM), both drugs caused similar
      inductions of reductase activity, reductase protein, and reductase mRNA. Under
      all conditions, the drugs induced similar changes in the ratio of mRNA/protein
      suggesting that Simva and Atorva have similar effects on both transcriptional and
      post-transcriptional regulatory machinery. Moreover, reductase in cells treated
      with Simva or Atorva for 22 h responded similarly to subsequent challenge with 25
      hydroxycholesterol. Finally, we measured the ability of the two reductase
      inhibitors to reduce ApoB secretion by HepG2 cells. Simva and Atorva at 0.5
      microM inhibited ApoB secretion nearly identically, 38% and 42% respectively. We
      conclude that these two drugs induce similar adaptive responses in cells and that
      their actions are qualitatively and mechanistically identical. Human studies have
      shown that plasma is cleared of Atorva much more slowly than it is of Simva. The
      large pharmacokinetic difference in man, rather than some difference in
      mechanism, is the most likely explanation for the finding that the equipotent
      dose ratio for cholesterol lowering in humans of Simva to Atorva is about 2/1.

PMID- 9512652
TI  - Secretory and cytosolic phospholipases A2 are activated during TNF priming of
      human neutrophils.
AB  - Cytokines alter neutrophil (PMN) function during inflammation, and Tumor Necrosis
      Factor (TNF) in vitro primes PMN such that receptor-mediated stimulation causes
      markedly enhanced release of arachidonic acid. We hypothesized that two Ca(2+)
      dependent PLA2's in PMN might be activated during priming of the cell, thus
      affecting arachidonate release. A low molecular weight, secretory PLA2 was
      identified by enzymatic activity in the cell free supernates of primed or
      stimulated PMN, and in PMN disrupted by nitrogen cavitation. The enzymatic
      activity was calcium-dependent, acid stable, destroyed by dithiothreitol, and
      blocked by anti-sPLA2 antibodies. TNF caused secretion of sPLA2 and also caused
      an increase in cell-associated sPLA2 enzymatic activity. Activation and release
      were maximal with fMLP stimulation of TNF-primed PMN. Neutrophils also contained
      a cytosolic PLA2 (cPLA2) characterized by enzymatic activity which was calcium
      dependent, enhanced by dithiothreitol, and blocked by anti-cPLA2 antibody. TNF
      caused a doubling of cPLA2 enzymatic activity which was associated with
      phosphorylation of the enzyme as judged by a migration shift on Western blots.
      Thus, TNF priming of human PMN caused marked increase in fMLP stimulated AA
      release in parallel to enhanced activity of two different PLA2's.

PMID- 9512653
TI  - Ligand conduction and the gated-pore mechanism of transmembrane transport.

PMID- 9512654
TI  - A computer perspective of membranes: molecular dynamics studies of lipid bilayer
      systems.

PMID- 9512655
TI  - Molecular cloning and analysis of the 5'-flanking region of the human bone
      morphogenetic protein-6 (BMP-6).
AB  - We cloned a genomic fragment of the 5'-flanking region of the gene encoding bone
      morphogenetic protein-6 (BMP-6) and assessed its promoter activity. Primer
      extension revealed the presence of one major transcription start site 178 bp
      upstream of the translation start site. The promoter region lacked a canonical
      TATA box but did contain a GC-rich region. A putative tramtrack responsive
      element, a Drosophila transcriptional factor regulating the segment polarity, was
      found in the promoter region. Known steroid hormonal responsive elements,
      however, were not found. Although BMP-6 is classified as a member of the vgr-1
      family, the structure of the promoter was similar to that of BMP-2 and 4.

PMID- 9512656
TI  - Structural and functional characterization of the mouse c-met proto-oncogene
      (hepatocyte growth factor receptor) promoter.
AB  - The c-met gene encoding Hepatocyte Growth Factor Receptor is predominantly
      expressed in epithelial cell types and overexpressed in a variety of human and
      mouse neoplastic tissues and cell lines. To understand the molecular mechanisms
      of the transcriptional regulation of this gene, we have cloned and functionally
      characterized the mouse c-met promoter region. Transient transfection analysis
      using a series of 5'-end deletion met-CAT chimeric constructs in epithelial (C
      33A) and fibroblast (NIH3T3) cell lines demonstrated that the c-met promoter acts
      in a cell-type specific manner. These experiments also localized functionally
      important regulatory regions at -1390 to -279, relative to the transcription
      start site, which exert repressive activity, and at -278 to -77 which exhibit
      enhancing effects on c-met promoter activity. Further analysis by electrophoretic
      mobility shift assays using specific competitors and antibodies identified Sp1
      protein binding to two cognate response elements at -221 and -124 within the
      enhancer region. Cotransfection experiments revealed that Sp1 stimulated promoter
      activity of the met-CAT constructs containing the two Sp1 binding sites. These
      results demonstrate that Sp1 is actively involved in the transcriptional
      regulation of the c-met promoter.

PMID- 9512657
TI  - Cloning and expression of the chicken 25-hydroxyvitamin D3 24-hydroxylase cDNA.
AB  - Using a cDNA probe from the rat 24-hydrovitamin D3 24-hydroxylase, the chicken 25
      hydroxyvitamin D3 24-hydroxylase cDNA has been isolated from a chicken kidney
      lambda gt11 library. The high degree of similarity with the mammalian 24
      hydroxylase cDNAs strongly supports the belief that it is the chicken 25
      hydroxyvitamin D3 24-hydroxylase cDNA. The deduced amino acid sequences are also
      very well conserved and 325 of them are identical among the four known 25
      hydroxyvitamin D3 24-hydroxylases. This cDNA expressed in E. coli produces 24
      hydroxylase activity.

PMID- 9512658
TI  - Cloning and characterization of the rat MAdCAM-1 cDNA and gene.
AB  - A cDNA clone for rat MAdCAM-1 homologue was isolated from mesenteric lymph nodes
      by RT-PCR using primers prepared from the exon sequences of the gene isolated
      from a genomic library of the WKAH rat, using mouse cDNA as a probe. A 1279 bp
      cDNA fragment contained an open reading frame (ORF) for a protein of 394 amino
      acids. Homology of nucleotide sequences between the mouse and rat MAdCAM-1 ORF
      was 85.1% with an amino acid identity of 80.5%. The rat MAdCAM-1 had two
      immunoglobulin-like domains, a mucinlike domain and the third immunoglobulin-like
      domain with a homology to alpha 3 domain of the rat MHC class I molecule.
      Northern blot analysis demonstrated transcripts in Peyer's patches and mesenteric
      lymph nodes but not in spleen. Organization of the gene in the rat was similar to
      that in the mouse, consisting of 5 exons located at about a 4 kbp genomic region.

PMID- 9512660
TI  - Sequence and expression analysis of a Drosophila gene product related to the tre
      oncogene.
AB  - We report the sequence and expression of a Drosophila cDNA that shows similarity
      to a portion of the tre oncogene. The deduced encoded protein, DRN-TRE, contains
      residues that are highly conserved across a wide phylogenetic spectrum. The
      temporal and spatial transcription pattern of DRN-TRE suggest that it functions
      in a broad range of tissues.

PMID- 9512659
TI  - cDNA cloning of a new member of the FTZ-F1 subfamily from a rainbow trout.
AB  - We describe here cDNA cloning of an orphan nuclear receptor family member, tFZR1,
      which has a FTZ-F1 box. The amino acid sequences of the zinc finger domain and
      the FTZ-F1 box has 92.8% and 100% identity, respectively, with those of zebrafish
      FTZ-F1. On the other hand, the overall homology between tFZR1 and zebrafish FTZ
      F1 is low (33.0%). The results indicate that tFZR1 is a new member of fushitarazu
      factor 1 (FTZ-F1) subfamily.

PMID- 9512662
TI  - Structural and phylogenetic analyses of RGD-CAP/beta ig-h3, a fasciclin-like
      adhesion protein expressed in chick chondrocytes.
AB  - A cDNA for RGD-CAP/beta ig-h3 was cloned from a chick embryo chondrocyte cDNA
      library. The deduced amino acid sequence showed that the chick RGD-CAP/beta ig-h3
      is 76-77% identical with human, mouse and pig forms of the protein, and 43%
      identical with human and mouse osteoblast specific factor 2 (OSF2). RGD-CAP/beta
      ig-h3 contained four internal repeat domains and two highly conserved sequences
      (H1 and H2) in each repeat. Chick RGD-CAP/beta ig-h3, as well as the mammalian
      RGD-CAP/beta ig-h3, contained an RGD sequence, which may serve as a recognition
      sequence for integrins, in the fourth repeat. Database searches revealed that the
      H1 and H2 sequences are conserved in some secreted or membrane proteins of
      several species including mammals, insects, sea urchins, plants, yeast and
      bacteria. Phylogenetic analysis showed that a portion of the common ancestor gene
      for RGD-CAP/beta ig-h3 and OSF2 was duplicated to form four repeat domains before
      the separation of the genes followed by the divergence of vertebrate species.

PMID- 9512661
TI  - Two unique 5' untranslated regions in mRNAs encoding human 14-3-3 zeta:
      differential expression in hemopoietic cells.
AB  - In this report, we describe the identification and characterization of a novel 14
      3-3 cDNA using the polymerase chain reaction and the screening of a human bone
      marrow cDNA library. This cDNA encodes the zeta isoform of 14-3-3 and contains a
      novel 5' untranslated region (UTR) that is G + C rich and only 50% identical to
      the 5' UTR in the human placental 14-3-3 zeta cDNA, suggesting that 14-3-3 zeta
      is encoded by at least two mRNAs. Using specific probes to the 5' UTRs of bone
      marrow and placental 14-3-3 zeta cDNAs, we studied the expression of each
      transcript in human hemopoietic cells at various stages of differentiation in the
      myeloid and lymphoid lineages. Differences in the expression of the bone marrow
      and placental 14-3-3 zeta transcripts were found, the most notable being the
      markedly decreased expression of both 14-3-3 zeta transcripts in HL-60 myeloid
      leukemic cells. Western blot analysis of 14-3-3 zeta levels in HL-60 cells
      revealed correspondingly decreased levels of 14-3-3 zeta protein compared to
      Jurkat cells. The differences among cell types of relative expression of the two
      14-3-3 transcripts may reflect normal regulatory patterns, while the strikingly
      decreased expression of both types in HL-60 are more likely to be reflective of
      its multiple genetic abnormalities which contribute to its transformed phenotype.

PMID- 9512663
TI  - Cloning and expression of a cDNA encoding the large subunit of duck replication
      factor C.
AB  - A cDNA encoding an avian homologue of the large subunit of replication factor C
      (RFC-L) has been cloned from a duck liver cDNA expression library prepared in
      bacteriophage lambda. The full length cDNA encodes a protein with a predicted
      size of approximately 130 kDa, consistent with the size of the polypeptide
      detected in duck liver. The duck RFC-L amino acid sequence shares 66.4% and 68.4%
      identity with mouse and human RFC-L proteins, respectively. We identified a 4kb
      RFC-L mRNA expressed in most duck tissues.

PMID- 9512664
TI  - Isolation, molecular characterization, and tissue-specific expression of a novel
      putative G protein-coupled receptor.
AB  - We isolated a 40 kDa integral membrane protein (p40) from human erythrocyte
      ghosts by affinity chromatography, using a C-terminal peptide of stomatin, and
      obtained partial sequences which enabled us to isolate two full-length cDNAs from
      human bone marrow and fetal brain cDNA libraries. The cDNA sequences were
      identical and encoded a novel putative G protein-coupled receptor (399 amino
      acids). Northern and RNA dot blot analyses demonstrated that the major 4.8 kb
      transcript is predominantly expressed in brain. In situ hybridization studies of
      tissue sections revealed high expression in neurons of the brain and spinal cord,
      in thymocytes, megakaryocytes, and macrophages.

PMID- 9512665
TI  - Molecular cloning and characterization of the gene encoding glutathione reductase
      in Brassica campestris.
AB  - We have isolated the Brassica campestris cDNA encoding glutathione reductase of
      502 amino acid residues with molecular mass of 54.5 kDa. The deduced amino acid
      sequences were 92.2%, and 79.5% identical to those of Arabidopsis thaliana, and
      pea, respectively. As expected, it exhibited a high degree of conservation within
      the region responsible for the redox reaction and for the binding of GSSG or
      NADPH. The gene was highly inducible by ozone fumigation or by paraquat
      treatment.

PMID- 9512666
TI  - Molecular identification of glutathione synthetase (GSH2) gene from Saccharomyces
      cerevisiae.
AB  - The hypothetical protein YOL049w on the chromosome XV was identified to be the
      structural gene for glutathione synthetase (GSH2) of Saccharomyces cerevisiae.
      Translational initiation site was identified by making the GSH2-lacZ fusion. The
      GSH2 gene contained an open reading frame (1473 bp) with 491 amino acids, and
      molecular weight of the GSH2 gene product was calculated to be 55,812.
      Glutathione synthetase activity in transformant carrying the GSH2 gene with
      multicopy plasmid increased approximately 4-fold. The GSH2 gene was not essential
      for growth of yeast cell, and glutathione was not detected from the gsh2
      disrupter.

PMID- 9512667
TI  - The deduced primary structure of a ribosomal protein S4 from Trypanosoma cruzi.
AB  - Two cDNA clones encoding a protein homologous to ribosomal protein S4 from the
      protozoan parasite Trypanosoma cruzi were isolated and characterized. Both clones
      potentially encode for an identical basic protein of 273 amino acids. Sequence
      comparisons with other species indicate that this protein is highly conserved.
      Hybridization studies are consistent with the occurrence of two genes in T. cruzi
      encoding this ribosomal protein. An RNA of approximately 1 kb was present in both
      exponentially growing and stationary phase derived epimastigotes, and no
      significant differences were detected in its steady state concentration.

PMID- 9512668
TI  - Molecular cloning and sequencing of the cDNA of cop1 gene from Pisum sativum.
AB  - Cop1 protein plays an important role in seedling development of higher plants.
      The cDNA of cop1 gene from pea (Pisum sativum) was cloned and sequenced. Cop1
      protein of pea is predicted to have 672 amino acids and a molecular mass of 76
      kDa. Sequence comparison between Cop1 proteins of pea and Arabidopsis thaliana
      revealed that the two Cop1 proteins were highly homologous in the regions with
      functional domains and at the C-terminus. Immunoblotting performed with
      polyclonal antibodies against recombinant Cop1 of pea showed that Cop1 protein
      was present in seedlings germinated both in light and darkness.

PMID- 9512669
TI  - Correct targeting of a vacuolar tobacco chitinase in Saccharomyces cerevisiae-
      post-translational modifications are dependent on the host strain.
AB  - The chitinase gene FB7-1 of Nicotiana tabacum cv. samsun line 5 was expressed in
      the two Saccharomyces cerevisiae strains, INVSC2 and H4, under the control of the
      GAL1 promoter from S. cerevisiae and a multicopy plasmid vector. Both yeast
      strains express the plant gene as enzymatic active proteins. In transformants of
      the strain INVSC2, 94% of the total plant chitinase is contained inside the
      cells, probably within the vacuole which has been confirmed by subcellular
      fractionation as well as immunohistochemical experiments. This retention inside
      the cells is due to the C-terminally located 7 amino acids long vacuolar
      targeting peptide of the prochitinase. When this sequence was removed, chitinase
      was transported into the culture medium. Pulse-chase experiments revealed that
      during translation in transformants of both yeast strains one chitinase
      polypeptide can be immunoadsorbed with specific antibodies. In the case of INVSC2
      transformants, newly formed chitinase is modified in a 60 min chase to slightly
      increase its molecular mass, whereas in H4-transformants the molecular mass
      constantly remained 32 kDa. By Western blot analysis two chitinase corresponding
      polypeptides of 32 and 37 kDa were accumulated in the culture medium of both
      transformants carrying the chitinase gene without the vacuolar targeting
      sequence. The larger one was very likely O-glycosylated. Whereas, both
      polypepitdes were also detected in cell extracts of the H4-transformant, only the
      smaller one was found in the INVSC2-transformant. The plant chitinase passed
      through the endoplasmic reticulum on its way to the vacuole. The N-terminal
      signal peptide responsible for the uptake into the endoplasmic reticulum is
      cleaved correctly. However, cleavage of the vacuolar targeting peptide located at
      the C-terminus, to give the mature chitinase is obviously influenced by the
      genetic background of the host strain. In INVSC2-transformants chitinase
      accumulates in its mature form whereas both the polypeptides of H4-transformants
      retain their vacuolar targeting peptide. Our results demonstrate that in the case
      of plant class I chitinase, the plant sorting signal is recognized in yeast cells
      but post-translational modifications are influenced by the host strain.

PMID- 9512670
TI  - Synergistic increase in c-fos expression by simultaneous activation of the
      ras/raf/map kinase- and protein kinase A signaling pathways is mediated by the c
      fos AP-1 and SRE sites.
AB  - Expression of the c-fos proto-oncogene is induced by numerous stimuli some of
      which are transmitted through the Ras/Raf/MAP kinase or the cAMP-dependent
      protein kinase (PKA) pathways. The effect of cell-specific interactions between
      these pathways on c-fos expression was investigated by exposing quiescent NIH3T3
      cells to serum, forskolin, or a combination. Co-stimulation with serum and
      forskolin resulted in a more than additive increase in c-fos transcription.
      Synergistic increase in c-fos promoter activity was also observed in transient
      transfection studies after co-stimulation with serum plus forskolin or co
      transfection with c-Raf and PKA expression plasmids. Analysis of the cAMP
      signaling pathway revealed that the synergy was neither due to an increase in PKA
      activity nor to Ser-133 phosphorylation/activation of CREB. The activation status
      of the MAP kinases ERK1 and ERK2 in co-treated cells was comparable to that in
      serum-treated cells. Co-stimulation with forskolin did not alter the
      phosphorylation state of Elk-1 compared to serum-induced phosphorylation of Elk
      1. Deletion of c-fos promoter elements previously shown to be important for
      regulation of c-fos expression in response to mitogens indicates a role for SRE
      and FAP-1 elements.

PMID- 9512671
TI  - Lack of increased cardiac toxicity with sequential doxorubicin and paclitaxel.

PMID- 9512672
TI  - Clinical studies in non-small cell lung cancer: the CALGB experience.
AB  - Since 1984, the Cancer and Leukemia Group B (CALGB) has focused its clinical
      research in stage IV non-small cell lung cancer (NSCLC) on investigations of new
      agents and combinations. Currently, efforts are aimed at identifying non
      cisplatin-based combinations with an increased therapeutic index. In stage III
      disease multimodality therapies have been pursued. Dillman et al. reported a
      study comparing standard radiotherapy versus induction chemotherapy followed by
      radiotherapy in patients with unresectable stage III NSCLC. The chemotherapy
      treated patients were found to benefit with a 4-month increase in median survival
      time compared with patients receiving radiotherapy alone (13.8 vs. 9.7 months)
      and an increased 3-year survival rate of 23% versus 11%. This was the first
      randomized cooperative group study demonstrating a survival advantage resulting
      from the use of induction chemotherapy in locoregionally advanced NSCLC. In a
      subsequent study, the administration of additional "posterior" chemotherapy was
      not found to be feasible because of early disease progression and toxicity, while
      the administration of induction chemotherapy followed by concomitant
      chemoradiotherapy was feasible; therefore, the latter approach was studied
      further in a randomized phase III setting. This study compared a standard of two
      cycles of cisplatin and vinblastine followed by radiotherapy with an experimental
      arm of cisplatin and vinblastine followed by radiotherapy and concomitant
      carboplatin. Accrual to this study has been completed and results are expected in
      the near future. In resectable stage III disease, studies have focused on the
      optimal sequencing of multimodality therapy. A randomized study comparing
      standard regional therapy with radiotherapy and surgery versus a previously
      piloted approach combining chemotherapy, surgery, and radiotherapy was closed
      prematurely due to poor accrual. The next generation of studies in stage III
      NSCLC will focus on the integration of new chemotherapy agents into the treatment
      armamentarium for NSCLC. A randomized phase II study investigating paclitaxel,
      gemcitabine, and vinorelbine in combination with cisplatin in the induction
      setting and as concomitant chemoradiotherapy has recently been activated.

PMID- 9512673
TI  - The efficacy of neoadjuvant chemotherapy compared to postoperative therapy in the
      treatment of locally advanced breast cancer.
AB  - The current approach to the treatment of locally advanced breast cancer is
      sequential chemotherapy, surgery and/or radiation, and consolidation
      chemotherapy. Although significant tumor response is seen with this regimen,
      there are few studies that compare this approach to postoperative chemotherapy.
      The purpose of this study was to compare the disease-free and overall survival of
      patients with locally advanced breast cancer treated with neoadjuvant
      chemotherapy and surgery to patients treated with surgery followed by adjuvant
      chemotherapy. Ninety-four patients with stage IIB, IIIA, and IIIB breast cancer
      were treated with a standardized chemotherapy regimen. The first group, 60
      patients who were followed prospectively, was treated with neoadjuvant
      chemotherapy (NCT) consisting of vincristine, prednisone, cytoxan, methotrexate,
      and 5-FU (CVFMP) followed by surgery and consolidation chemotherapy with
      adriamycin. The second group, 34 patients evaluated retrospectively, had surgery
      followed by postoperative chemotherapy (PCT) with CVFMP followed by adriamycin.
      Overall median follow-up was 38 months. In the NCT group, 45/60 (75%) patients
      had a clinical response to induction therapy and the median reduction in tumor
      size was 50%. The rates of local recurrence, distant recurrence, and death from
      disease were similar in the two groups. The time to local recurrence was similar
      for the two groups. However, the median time to distant recurrence was shorter in
      the NCT group (19 month vs. 31 months, p = NS). Overall median survival among the
      NCT patients was shorter than for the PCT group (30 vs. 47 months, p = NS). The
      current study suggests that postoperative therapy is comparable to a neoadjuvant
      regimen in patients with locally advanced breast cancer with regard to local
      recurrence, distant recurrence, and overall survival.

PMID- 9512674
TI  - Efficacy of intravenous granisetron to control nausea and vomiting during
      multiple cycles of cisplatin-based chemotherapy.
AB  - The safety and efficacy of granisetron (10 micrograms/kg and 40 micrograms/kg)
      were evaluated during a second (n = 393) and third (n = 200) cycle of
      chemotherapy in this multicenter, double-blind, randomized, parallel-group study.
      Granisetron was administered as a single intravenous dose before the start of
      cisplatin chemotherapy (> or = 60 mg/m2). Total control (no vomiting, no
      retching, no nausea, and no use of antiemetic rescue medication) after the first
      24 hr following chemotherapy was achieved in 40% and 49% of patients in Cycles 2
      and 3, respectively, for the 10 micrograms/kg group, and in 42% and 38% of
      patients in Cycles 2 and 3, respectively, for the 40 micrograms/kg group. Both
      dose levels of granisetron were well tolerated. The results demonstrate
      comparable efficacy between the 10 micrograms/kg and 40 micrograms/kg doses of
      granisetron in preventing nausea and vomiting during repeat cycles of high-dose
      cisplatin-based chemotherapy. The results of this study show that granisetron 10
      micrograms/kg is safe and well tolerated, and remains effective with repeat cycle
      use.

PMID- 9512675
TI  - New pharmacological strategies in the management of cancer pain.

PMID- 9512676
TI  - Hematopoietic progenitor cell transplantation in breast cancer: current status
      and future directions.
AB  - Breast cancer remains the second leading cause of cancer death despite numerous
      advances in medical science. In vitro, preclinical, and clinical trials have
      shown that chemotherapy dose intensity is an important component of therapy. Many
      clinical trials addressing the use of high-dose chemotherapy and hematopoietic
      cellular rescue have been conducted over the past decade. Early trials undertaken
      in heavily pretreated patients who had metastatic disease were associated with
      high treatment-related mortality rates; good response rates were noted but
      overall survivals were short. Subsequent technological advances, including the
      use of recombinant hematopoietic growth factors and peripheral blood progenitor
      cells as the source of cellular rescue, have dramatically lowered the morbidity
      and mortality of the procedure, as well as shortened hospital stay and markedly
      reduced cost. As a result, the high-dose chemotherapy approach has been used
      earlier in the disease course, both in patients with metastatic disease who were
      responding and in the adjuvant setting in patients at high risk for relapse.
      Results of many of these phase II trials are extremely encouraging, and phase III
      prospective, randomized trials comparing autotransplant to conventional
      approaches are currently under way. This review discusses past, current, and
      future initiatives of this modality. Included is a discussion of new preparative
      regimens, the addition of agents such as biochemical modifiers to enhance
      antitumor activity, and issues regarding timing of autotransplant, stem cell
      technology, use of allogeneic stem cells, and posttransplantation therapies.

PMID- 9512677
TI  - Cytogenetics of leukemia.

PMID- 9512678
TI  - Should cost be considered in the overall evaluation of phase II clinical trials
      of new antineoplastic therapies? A response.

PMID- 9512679
TI  - Costs of cancer research: financial and personal.

PMID- 9512680
TI  - [Recent advances in research on SMANCS].
AB  - During the past five years we observed many advances in the study of the polymer
      drug, "SMANCS". This first polymeric drug was approved by the Japanese Ministry
      of Health and Welfare in 1994 as a drug for primary liver cancer, in which the
      arterial injection of oily formulation in Lipiodol (a lipid contrast medium) is
      the standard procedure. The advantage of this tactic is the most extraordinary
      cancer targeting efficiency with the least systemic side effect and very
      prolonged slow release of SMANCS. The mechanism of tumor selective accumulation
      of SMANCS and polymeric drugs in general is discussed in view of the so called
      EPR (enhanced permeability and retention) effect of solid tumor. The mode of
      action of SMANCS at the cellular level seems to accompany the generation of
      superoxide radical which damages DNA; strand break and modification of guaninine
      by 8-hydroxylguanine. Immunological potentiation involves either the cellular (M
      phi, T-cell, NK-cell) or molecular level (induction of cytokines, including
      interferon gamma). The in vivo effect of SMANCS is most pronounced in the tumor
      vessels where more concentrated SMANCS is accessible due to the EPR effect, and
      perhaps the generation of O2.-. Nitric oxide generated by both inducible form of
      NO synthase (iNOS) by the infiltrated macrophages and NOS of endothelial cells,
      and superoxide from SMANCS will readily react to form peroxynitrite (O2- + NO-
      >ONOO-), which is a very potent cytotoxic molecule and will damage (nitrate and
      oxidize) DNA and proteins. Thus, tissue damage and vascular injury or collapse
      will be the principle tumor toxic mechanism of SMANCS at tissue level. The dose
      of SMANCS (or grade I-IV tumor filling) and tumor regression parallel each other,
      and a profile of AFP-value and technical issues of SMANCS/Lipiodol administration
      intraarterially are also discussed.

PMID- 9512681
TI  - [Targeted chemotherapy of hepatocellular carcinoma with SMANCS/Lipiodol--how to
      use SMANCS/Lipiodol].
AB  - The first drug only for arterial injection, SMANCS/Lipiodol, which offers
      targeted chemotherapy for hepatocellular carcinoma (HCC), now commercially
      available. Based on our experience using SMANCS/Lipiodol for 424 patients with
      HCC, the golden standard of how to use SMANCS/Lipiodol for complete necrosis of
      tumor was described. The initial dose of SMANCS/Lipiodol was varied 2 to 6 mg per
      body, mainly depending on the size of the tumor. All feeding arteries of HCC have
      to be verified on angiogram, and the drug must be injected via an adequate
      artery. Sometimes, a tumor changes its feeding arteries. Additional
      administrations with an interval of one month were done till the entire tumor was
      filled with SMANCS/Lipiodol (grade 4). One or two months after achievement of
      grade 4, we must examine how much drug was removed from tumor on CT. If the
      entire tumor is not filled with the drug, further injections are recommended to
      maintain grade 4. Almost all tumors shrank in 3 to 4 months while maintaining
      grade 4. Frequent administration of low doses (1-3 mg per body) is recommended.
      Discontinvation of administration was done on the following findings; tumor size
      reduction of over 90% or complete disappearance of tumor stain. With arterial
      injection therapy of SMANCS/Lipiodol, survival of patients with unresectable HCC
      was prolonged, especially in 272 patients who were good candidates for therapy.
      (Those with Child C liver cirrhosis, with a tumor occupying all four segments of
      the liver, and/or with extrahepatic spread at initial arterial injection of the
      drug were excluded.) The 1, 2, 5, and 10 year survival rates were 83%, 58%, 34%,
      and 25%, respectively.

PMID- 9512682
TI  - [Effect of arterial administration of a high molecular weight anti-tumor agent
      styrene maleic acid neocarzinostatin for multiple small liver cancer].
AB  - To assess the characteristics of a zinostatin derivative, 29 patients with
      multiple hepatocellular carcinoma of 3 cm or less in diameter were treated with
      intra-arterial injection of the high molecular weight anti-tumor agent, styrene
      maleic acid neocarzinostatin, mixed with Lipiodol. Computerized tomography 3
      months after the first therapy showed complete accumulation of Lipiodol in 8
      patients (27.6%), 50% to 99% accumulation in 4 (13.8%), 10 to 49% in 10 (34.5%),
      and less than 10% in 7 (24.1%). After repeated injections, Lipiodol accumulation
      of the entire area of the original tumor was found in 11 patients (37.9%). The
      degree of Lipiodol accumulation depended on the angiographic vascularity of the
      tumor and on the images of computerized tomogram during arterial portography.
      Although complete accumulation of Lipiodol was found in all tumors in 10 (58.8%)
      of the 17 patients with well-demarcated round-shaped hypervascularity, only one
      (8.3%) of 12 patients with ill-demarcated tumors could achieve complete
      accumulation of the Lipiodol in the tumors. Taking into account the fact that
      hypervascularity on angiograms is closely correlated with the degree of Lipiodol
      accumulation on computerized tomograms obtained later, well-demarcated round
      shaped liver cancer is the best candidate for styrene-maleic acid
      neocarzinostatin therapy among various stages of liver cancer.

PMID- 9512683
TI  - [Arterial infusion chemotherapy with SMANCS-Lipiodol for multiple hepatocellular
      carcinoma].
AB  - Fifty-five patients with hepatocellular carcinoma were treated with oily
      anticancer agent SMANCS dissolved in Lipiodol (SMANCS-LPD). The local response
      rate after the first arterial infusion in all patients was 39%, against 63% in 27
      patients with Lipiodol accumulation occupying more than two thirds of tumor
      areas. The infusion therapy with SMANCS-LPD is adapted for a vascular-rich
      hepatocellular carcinoma. An infusion of 4 mg of SMANCS was ineffective for
      patients with tumors distributing in bilateral lobes of liver. Thus, an increase
      of infusion dosage or repeated infusions were recommended for such cases.

PMID- 9512684
TI  - [Repeated arterial infusion of zinostatin stimalamer using port for advanced
      hepatocellular carcinoma].
AB  - Four patients with advanced hepatocellular carcinoma were treated by repeated
      arterial infusion of zinostatin stimalamer (SMANCS). Every 4 weeks, 4 mg of
      SMANCS and 4 ml of Lipiodol were administered via the proper hepatic artery using
      an implantable arterial port. Three patients with advanced liver cirrhosis (Child
      B or C) could no longer be treated after 2 or 3 courses of SMANCS infusion
      because of hepatic failure. In the remaining patient also with compensated liver
      cirrhosis (Child A), a partial response was observed after 5 courses of chemo
      infusion, but we discontinued infusion of SMANCS because of hepatic failure. To
      assess the usefulness of SMANCS for repeated arterial chemo-infusion by the port,
      we evaluated 103 patients with advanced HCC treated by Lipiodol emulsion mixed
      with 70 mg of epirubicin (EPI) using a port. An average course was 11 arterial
      infusions, and the overall response rate was 40%. One-year survival rates were
      62% in Child A, 59% in Child B, and 53% in Child C. Compared with Child A and B
      patients, both elevation of serum total bilirubin levels and decrease of serum
      albumin levels were observed after 9 months in Child C patients. In conclusion,
      SMANCS may have more severe hepatic toxicity in comparison with Lipiodol emulsion
      mixed with EPI.

PMID- 9512685
TI  - [Arterial infusion of SMANCS for multiple recurrent tumors after hepatic
      resection].
AB  - We investigated the possible side effects and efficacy of arterial infusion of
      SMANCS as compared to Lipiodol + epirubicin TAE for multiple recurrent tumors
      after hepatic resection. As a result, no significant difference in GOT, GPT, and
      total bilirubin was observed between the two groups. No significant difference
      was found in white blood cell count and platelet count, and there was no
      significant difference in clinical side effects between the two groups. Grade III
      response rates after arterial infusion of SMANCS were found in 4 patients
      (66.6%), and these results showed no significant difference as compared to
      Lipiodol + epirubicin TAE. Proper hepatic arterial infusion of SMANCS appeared to
      be useful in multiple recurrent tumors from the standpoints of safety and the
      rate of Lipiodol deposition.

PMID- 9512686
TI  - [Advantages and disadvantages of SMANCS-Lipiodol intrahepatic arterial infusion
      chemotherapy for unresectable hepatocellular carcinoma].
AB  - Though SMANCS-Lipiodol suspension has advantages over tumor regression, its
      disadvantages should also be considered: (1) Anaphylactic reaction due to its
      high molecular weight. (2) Since it readily destroys the tissue, a smaller dose
      and repeated administration are required. (3) Due to its low viscosity, it easily
      enters the arterioles and causes damage even to the extrahepatic organs. When
      this drug is infused into the left hepatic artery in subsegmental fashion, it
      enters the neighboring gastric tissues through the communication of the left
      hepatic and left gastric arteries, and this ultimately causes intractable gastric
      ulcers. Considering the above facts, this drug should be used carefully.

PMID- 9512687
TI  - [Results of SMANCS/Lipiodol injection therapy for multiple intrahepatic
      recurrence of hepatocellular carcinoma].
AB  - Hepatocellular carcinoma (HCC) often recurs in the remnant liver after
      hepatectomy. Treatment is often ineffective in cases of multiple recurrence. We
      treated 18 cases of multiple recurrence with SMANCS/Lipiodol injection (SML).
      Four patients were treated with SML once, 11 patients were treated twice, and
      each patient was treated with three or four times with SML. The Effective rate of
      the 1st SML was 30%, but the effective rate of the 2nd SML was 60% in the plasma
      tumor marker levels. The effective rate between unilobular recurrence and
      bilateral recurrence was the same. A complete response was obtained in 2 cases,
      and partial response in 2 cases. The effective rate of SML was 4/18 (22.2%).
      These effective cases suffered a recurrence within a year. The cumulative
      survival rate at the end of the 24th month was 42.4%. Overall survival was
      significantly higher in the group with SML than in the group with TAE or TAI with
      the multiple recurrence. SML may be effective in early recurrence because these
      recurrent nodules are vascular-rich and there is much lipiodol accumulation.
      SMANCS/lipiodol injection therapy is expected to be an effective treatment in
      cases of early multiple recurrence after hepatectomy.

PMID- 9512688
TI  - [Arterial infusion of SMANCS-Lipiodol for advanced hepatocellular carcinoma].
AB  - Twenty-four patients were treated with arterial infusion of SMANCS dissolved in
      Lipiodol. Twenty of these patients had HCC with the main trunks of portal vein
      occluded by tumor, and four patients had severe cirrhosis and multiple HCC. The
      actual dose of SMANCS administered each patient ranged from 4 to 6 mg. Side
      effects occurred in 50%. Severe side effects such as shock and shivering
      chilliness were observed in 18%. The differences between the values of hepatic
      functional serum indexes obtained before and after treatment with SMANCS were
      small and transient. With regard to the therapeutic response of the arterial
      infusion of SMANCS, the mean survival time was approximately 2.8 months. It was
      suggested that the more effective administration of SMANCS was combination of the
      arterial infusion of SMANCS-Lipiodol with TAE at the level of the right hepatic
      artery of left hepatic artery for multiple HCC.

PMID- 9512689
TI  - [Evaluation of transcatheter hepatic segmental or subsegmental infusion of SMANCS
      for treatment of hepatocellular carcinoma].
AB  - A total of seventeen patients with hepatocellular carcinoma (HCC), nineteen HCCs,
      who underwent as an initial treatment transcatheter hepatic segmental or
      subsegmental arterial administration of SMANCS alone for hepatocellular carcinoma
      (HCC), were studied to evaluate the efficacy and complication of that treatment.
      The initial treatments provided CR in eight patients (47%), and repeat
      administrations of SMANCS achieved CR in an additional four patients (24%). The
      initial treatment provided a dense deposit of Lipiodol in the twelve tumors
      (63%), in five of which Lipiodol was thereafter washed out in some portions of
      the tumor. Complete necrosis was obtained in nine (75%) of fourteen hypervascular
      tumors, and in two (40%) of five intermediately vascular or hypovascular tumors.
      Segmental or subsegmental administration of SMANCS was well tolerated with self
      controlled abdominal pain or fever well responding to medication. Ascites was
      seen in three cases, and atrophy of the segment infused occurred in five
      patients. Cholinesterase significantly reduced at one week and one month, then
      recovered to baseline two to three months after initial treatment. The cumulative
      survival rates were 77% at 1 year, 66% at 2 years, and 53% at 5 years in the
      whole patients. The survival rate was 100% at 5 years in the Child A group. In
      the patients who obtained CR using SMANCS alone, the survival rates were 89% at 1
      year, 74% at 2 years and 56% at 5 years. Although this method may transiently
      deteriorate hepatic function, segmental or subsegmental administration of SMANCS
      may be an excellent therapeutic method for treatment of HCC and promising for use
      in properly selected patients.

PMID- 9512690
TI  - [Intra-arterial infusion of SMANCS for treatment of patients with hepatocellular
      carcinoma--adverse reactions and complications].
AB  - Although intra-arterial infusion of SMANCS has been demonstrated to be highly
      effective for treatment of patients with hepatocellular carcinoma, it is reported
      to cause critical adverse reactions and complications. We examined the adverse
      reactions of SMANCS on the hepatic artery in 78 patients with hepatocellular
      carcinoma, who were infused with SMANCS from right, left or proper hepatic artery
      at our hospital. SMANCS caused right hepatic artery occlusion in 15 patients
      (19%) and the average amount of infused SMANCS was 6.8 mg. The tumor volume in
      the artery occluded patients was smaller than that in the artery non-occluded
      patients. Then, the mechanism by which SMANCS caused arterial occlusion was its
      induction of arterial injuries by excess infusion. When SMANCS was infused to
      whole liver, it induced decreased hepatic functional reserve and liver atrophy,
      followed by delayed liver failure. Other adverse reactions were no different from
      those in patients infused with epirubicin-lipiodol emulsion.

PMID- 9512691
TI  - [Pathologic study of hepatocellular carcinoma treated by TAI and TAE with
      SMANCS].

PMID- 9512692
TI  - [Comparative studies on the antitumor activities and side effects of segmental
      SMANCS/Lip-TAE with segmental SMANCS/Lip-TAI for hepatocellular carcinoma].
AB  - We compared the effectiveness of treatments and the influence of side effects on
      liver function and clinical symptoms between segmental SMANCS/ Lip TAI and
      segmental SMANCS/Lip-TAE. The early tumor response rate of the group treated by
      TAI was 23.6%, and that of the group treated by TAE was 80.0%. In the group
      treated by TAE, the therapeutic effects were better in the nodular type than in
      the diffuse type of HCC, and we were also able to obtain a good tumor response
      rate on the multiple HCC and large HCC. However, there was no difference in the
      response period between the groups treated by TAI and TAE. In both groups, there
      were no significant differences in the appearance rate and degree of side
      effects. In conclusion, segmental SMANCS/Lip-TAE seemed to be an effective
      treatment for HCC without any serious complications.

PMID- 9512693
TI  - [SMANCS/TAE for hepatocellular carcinoma: comparison with SMANCS/TAI].
AB  - To evaluate the effects of SMANCS/TAE for hepatocellular carcinoma, AFP reduction
      rates, tumor reduction rates of SMANCS/TAE were compared with those of
      SMANCS/TAI. SMANCS is a stylene-maleic acid neocarzinostatin. TAE means
      transcatheter arterial embolization with gelatin sponge after SMANCS infusion and
      TAI means transcatheter arterial infusion of only SMANCS-iodized oil suspension.
      For evaluation of the AFP reduction rate, 13 SMANCS/TAEs were compared with 32
      SMANCS/TAIs. In these cases, pretreatment serum AFP levels were higher or equal
      to 100 ng/ ml. The average dose of SMANCS/TAE was 4.2 +/- 1.8 (S. D) mg and that
      of SMANCS/TAI was 3.9 +/- 1.8 (S. D) mg (N. S: t-test, p = 0.59). Student's t
      test revealed that the AFP reduction rate of SMANCS/TAE was not significantly
      superior to that of SMANCS/TAI (p = 0.78), and both AFP reduction rate of
      SMANCS/TAE and SMANCS/ TAI were not correlated with the dose of SMANCS. Tumor
      reduction rates of 12 SMANCS/TAEs and 14 SMANCS/TAIs on CT examination were
      calculated. The average dose of SMANCS/TAE was 4.5 +/- 1.9 (S. D) mg and that of
      SMANCS/TAI was 3.8 +/- 2.1 (S. D) mg (N. S: t-test, p = 0.29). The average tumor
      reduction rate of SMANCS/TAE was 25.3 +/- 30.1 (S. D)% and of SMANCS/TAI was 13.8
      +/- 29.1%. Student's t-test revealed the tumor reduction rate of SMANCS/TAE was
      not significantly larger than that of SMANCS/TAI (p = 0.33). AFP reduction rate
      and tumor reduction rate of SMANCS/TAE were not significantly different from
      those of SMANCS/TAI. Although the number of cases was not enough, these results
      suggest SMANCS/TAI should be applied for treatment of hepatocellular carcinoma
      rather than SMANCS/ TAE.

PMID- 9512694
TI  - [Outcome of TAE for hepatocellular carcinoma: comparative study of SMANCS-TAE and
      non-SMANCS/LpTAE].
AB  - The therapeutic effectiveness of transcatheter arterial embolization (TAE) with
      intraarterial infusion of SMANCS/lipiodol mixture was retrospectively compared to
      TAE with intraarterial infusion of epirubicin/lipiodol mixture in initial
      treatment of 54 patients with unresected hepatocellular carcinoma. The
      therapeutic effects were evaluated by the rate of tumor necrosis after the
      initial procedure and the cumulative survival rate. Eighteen patients were
      treated with SMANCS, and 36 patients were treated with epirubicin. There was no
      significant difference in patient background between the two groups; the hepatic
      functional reserve was not seriously disturbed in most of the patients, and
      multiple hepatic lesions were seen in half the patients. Complete tumor necrosis
      assessed by the imaging of dynamic CT one month after TAE was seen in
      approximately 40% of the cases in each group. Local recurrence was seen in half
      the patients after assessment of complete tumor necrosis within one year in both
      groups. There was no significant difference in survival period. There was also no
      significant difference of the frequency and degree of the side effects. In
      conclusion, no distinct difference of outcome was found in the two groups in this
      comparative study. Further studies in many cases over a longer period will be
      needed to elucidate the effects of SMANCS in TAE.

PMID- 9512695
TI  - [Significance of arterial infusion of SMANCS-dissolved Lipiodol in therapeutic
      strategies for hepatocellular carcinoma].
AB  - The arterial infusion of lipiodol (LPD) containing SMANCS (SMANCS/LPD) has been
      considered to be a tumor-targeting therapy for hepatocellular carcinoma (HCC). It
      is important to establish a role of this new therapy in systematic strategies for
      HCC. LPD has no embolic effect, and the lipophilic anti-cancer agent, SMANCS,
      suspended in LPD and delivered selectively in tumors, shows therapeutic effect.
      Accordingly, it is essential for therapeutic efficacy that HCC cells have a
      chemosensitivity to SMANCS. The maximum dose of SMANCS/LPD is 6 ml at one time,
      which is not sufficient for voluminous tumors. These are the disadvantages of
      SMANCS/LPD therapy. Furthermore, HCC tissues, in which lipiodol is retained, is
      limited to moderately differentiated, with large blood spaces. SMANCS/LPD is not
      effective for well- and poorly -differentiated HCCs, because blood spaces in
      these histological types are too small for SMANCS/LPD to be deposited. On the
      other hand, transcatheter arterial embolization therapy (TAE) is effective by
      occluding feeding artery with small pieces of gelatin sponge, and a much tumor
      necrosis is obtained by TAE at one time. However, HCC cells beneath and within
      the capsule, and invading outside the capsule, are viable, possibly due to
      backflow of blood via drainage vein. Tumor thrombi and tiny intrahepatic
      metastases also escape the TAE effect. Previously we reported the new therapy at
      the first time: the combination of arterial infusion of SMANCS/LPD and TAE
      (LpTAE). LpTAE has some therapeutic benefits of both therapies; SMANCS/LPD fills
      up a whole tumor, and part of the LPD flows out from the tumor, is trapped in the
      capsular invasion and microscopic metastatic foci with the necrotic change. LPD
      prevents regurgitation of blood flow in drainage vein, and promotes necrotic
      change. After LpTAE, Lipiodol CT shows 4 kinds of LPD-deposition pattern in HCC;
      the therapeutic effects of LpTAE are exactly evaluated by these patterns. For
      total necrosis, HCC nodule shows a complete type, in which the whole tumor shows
      a metallic density by lipiodol deposition. In other patterns, the LPD-deposited
      area in tumors generally shows necrosis, and non-LPD-deposited areas are viable.
      The second line of the therapies. PEIT or resection, can be selected by the LPD
      deposition pattern. We consider that the intraarterial infusion of SMANCS/LPD
      reinforces TAE, and LpTAE is one of the most effective therapies.

PMID- 9512696
TI  - [Comparison of therapeutic effects of SMANCS (+TAE) and Non-SMANCS/LpTAE].
AB  - Therapeutic effects of SMANCS and LpTAE were evaluated for hepatocellular
      carcinoma (HCC). Since June 1995, SMANCS has been used in 59 patients for their
      first treatment. LpTAE had been performed for HCC before introduction of SMANCS
      in our hospital, and 71 patients treated after 1992 were chosen for comparison
      with the therapeutic effect of SMANCS. Among the patients treated with SMANCS,
      complete and partial responses (CR and PR) were obtained in 24 cases (41%) and 17
      cases (33%), respectively. SMANCS accompanied by TAE was more effective than
      SMANCS alone. The effects did not depend on the level of the hepatic arterial
      branch at which SMANCS was administered. In patients treated with LpTAE, CR and
      PR were obtained in 12 cases (17%) and 18 cases (25%), respectively. SMANCS was
      significantly more effective than LpTAE. Because of our short experience with
      SMANCS, we could only show a two year survival rate. The one- and two-year
      survival rates for SMANCS were 71% and 57%, respectively. They were not
      significantly different from those for LpTAE, at 80% and 60%. Despite good
      results of treatment for HCC, a better prognosis could not be expected by SMANCS
      in this study. These results may be explained as follows. The evaluating the
      cause of death within two years after first treatment, hepatic failure was more
      common in patients treated with SMANCS. After treatment by SMANCS, 11 patients
      (55%) died from hepatic failure. On the other hand, 4 patients (15%) died from
      hepatic failure after LpTAE. Although there is no significant difference of Child
      Pugh score, this may indicate that SMANCS has been used for patients with lesser
      hepatic reserve and this leads to early deaths in patients treated with SMANCS.
      However, because of the short experience in this study, further observation is
      necessary for precise evaluation of clinical efficacy of SMANCS.

PMID- 9512697
TI  - [Our initial experience with SMANCS in TAE for liver cancer].
AB  - To evaluate the efficacy and adverse reaction of SMANCS, we reviewed 10 cases
      treated by TAE with SMANCS among 896 cases treated by TAE for liver cancer during
      the past three years at our institute. Our criteria for using SMANCS were as
      follows: a) reduced effectiveness of past TAE with Lipiodol, hydrophilic drugs
      and gelatin sponge; b) sufficient caliber and blood flow in the hepatic artery;
      and c) good hepatic function. The 1- and 2-year survival rates after treatment
      with SMANCS were 50% and 25%, respectively. The 3- and 5-year survival rates
      after initial treatment (first TAE, etc.) were 40% and 20%, respectively. There
      were no significant complications in clinical course, however, subsequent hepatic
      arteriogram often showed arterial change that may interfere with further regional
      therapy for the liver.

PMID- 9512698
TI  - [Transcatheter arterial embolization with SMANCS and epiADM for hepatocellular
      carcinoma].
AB  - We have attempted transcatheter arterial embolization (TAE) with SMANCS and
      epiADM for 40 patients with hepatocellular carcinoma and evaluated its
      therapeutic effects and side effects. There were 7 cases of stage I disease, 10
      cases of stage II disease, 10 cases of stage III disease and 13 cases of stage IV
      disease. Patients underwent TAE superselectively following infusion of w/o
      emulsion of epiADM and SMANCS-lipiodol. No severe side effect was observed
      compared with conventional Lp-TAE except in one case with hepatic biloma after
      treatment. The overall response rate was 70%, and 54.5% in the patients with
      recurrent tumor after Lp-TAE. The serum AFP value decreased in 16 patients out of
      20 patients. Hepatic resection was performed in 2 patients after treatment, and
      no viable tumor cell was recognized in the specimen. Our result suggested that
      TAE with SMANCS and epiADM will contribute to improved therapeutic efficacy for
      hepatocellular carcinoma.

PMID- 9512699
TI  - [Treatment of hepatocellular carcinoma by segmental SMANCS Lipiodol-TAE].
AB  - Segmental SMANCS Lipiodol TAE (Seg. SMANCS Lp-TAE) using SMANCS was used to treat
      HCC in 58 patients and was evaluated in comparison with Seg. Lp-TAE using
      Epirubicin performed in 50 patients with respect to the course of atrophy of the
      embolized area, recurrence rate and side effects. On serial CT (Lp-CT) performed
      after TAE, in cases with P type in which the tumor is present in the periphery of
      the embolized area and showing Type I homogeneous accumulation of Lp within the
      tumor, the incidence of atrophy in the embolized area including the tumor was
      high and the recurrence rate was low. Although no significant difference in the
      recurrence rate was noted between the groups in which SMANCS and EPI were used,
      there were more cases with marked atrophy and a lower recurrence rate in the
      former. No difference was found in post-procedural side effects such as fever
      between the two groups, while hypotension was rarely observed during the
      procedure in the group in which SMANCS was used and was easily managed with
      intravenous steroids. The present results suggest that Seg. SMANCS Lp-TAE is an
      effective local treatment for HCC limited to a subsegment or segment.

PMID- 9512700
TI  - [Combination of transcatheter arterial infusion of SMANCS and embolization
      (SMANCS-TAE) for hepatocellular carcinoma].
AB  - Patients with unresectable hepatocellular carcinoma (hepatoma) with
      hypervascularity were treated by SMANCS-TAE, which was performed by a
      superselective catheterization technique to inject gelatin sponge particles after
      administration of SMANCS. In 24 of 30 (80%) patients of first hepatoma treated by
      SMANCS-TAE, Grade 4 was obtained after about 1.5 (1-3) courses. The 2-year
      survival rate was 33%. SMANCS-TAE appears to have the same potential and safety
      as Lipiodol-TAE, treated selectively. Moreover, we can reduce the course of
      treatment and obtain good QOL of hepatoma patients except in advanced cases (vp 3
      or T 4).

PMID- 9512701
TI  - [Subsegmental transcatheter hepatic arterial embolization under balloon occlusion
      of the corresponding hepatic vein with SMANCS].
AB  - Recently, subsegmental transcatheter hepatic arterial embolization under balloon
      occlusion of the corresponding hepatic vein has been performed to treat hepatic
      infarction in subregion hepatocellular carcinoma (HCC). Here, we report
      subsegmental transcatheter hepatic arterial embolization under balloon occlusion
      of the corresponding hepatic vein with styrene maleic acid neocarzinostatin
      lipiodol (SMANCS) (SMANCS-TAE under balloon occlusion of the corresponding
      hepatic vein). This study included 9 patients with HCC who underwent SMANCS-TAE
      under balloon occlusion of the corresponding hepatic vein. In all patients, the
      therapeutic effects (TE) were evaluated according to the criteria of direct
      response to liver cancer treatment on abdominal computed tomography (CT) 3 weeks
      after surgery. In 7 patients who could be followed for more than one year, there
      was no postoperative relapse at the site of treatment. Furthermore, this
      procedure facilitated the detection of accumulation of SMANCS not only in the
      tumor but also in the subregion of the tumor in patients with HCC involving
      immature arterial tumor neoplastic vessels. In patients with large HCC
      complicated by severe heart failure showing a poor general condition, this
      procedure allowed treatment to be completed without complication. SMANCS-TAE
      under balloon occlusion of the corresponding hepatic vein, which can also
      embolize the portal vein by applying targeting chemotherapy with SMANCS, may
      cause necrosis not only in the tumor but also in noncancerous liver tissues. This
      procedure may be an indication for a larger number of cases than standard TAE,
      facilitating more complete local treatment.

PMID- 9512702
TI  - [SMANCS-TAE combined with PEI in the treatment for hepatocellular carcinoma].
AB  - From January 1996 to August 1997, 24 patients with advanced hepatocellular
      carcinoma (HCC) equal to or more than 2 cm (mean +/- SD; 4.1 +/- 3.0 cm) in main
      tumor diameter were treated by SMANCS-TAE (20 cases) or SMANCS-TAI (4 cases)
      combined with PEI. Six cases had solitary lesion, 16 cases had multiple lesions,
      and 2 cases had massive lesions. After this combination therapy, 21 of 24 cases
      had complete tumor necrosis. During 3 to 19 months follow up period, 12 cases had
      cancer-free survival (SMANCS-TAI; 3 cases), and 9 cases had tumor recurrences (3
      cases were local recurrences and 6 cases involved new lesions). Two cases died of
      hepatic infarction and cancer death, however, the remaining 22 cases were
      surviving. SMANCS-TAE combined with PEI is useful treatment for advanced large or
      multiple HCC lesions in patients who are poor surgical risks.

PMID- 9512703
TI  - Stepwise selection of TetR variants recognizing tet operator 4C with high
      affinity and specificity.
AB  - The TetR PQ39 mutant exhibits a new recognition specificity for the tetO-4C
      operator, but the affinity is not sufficiently high for use in vivo. A stepwise
      selection of additional mutations by cassette mutagenesis with randomization of
      residues in the TetR alpha-helix-turn-alpha-helix motif (HTH) yielded mutant TetR
      EA37PQ39YM42 showing a similar affinity and increased specificity for tetO-4C as
      wild-type TetR for tetO. A set of mutants obtained by that approach revealed that
      the fourth residue of the HTH (Leu41), which points towards the core of the DNA
      binding domain in TetR, alters the recognition of base-pair 4, e.g. the mutant
      TetR LV41YM42 exhibits a new recognition specificity for tetO-4G. A small residue
      at the last position in the turn of the HTH increases the affinity and
      specificity of DNA binding of TetR mutants containing the PQ39 exchange. Thus,
      cooperation between residues at positions 37, 39, 41 and 42 in the HTH of TetR is
      necessary to optimize recognition of base-pair 4. We conclude that creating a new
      DNA recognition specificity in the HTH of TetR with high affinity for the tetO-4C
      operator variant requires exchanges altering flexibility and/or adjustment of the
      recognition alpha-helix to the target DNA in addition to the contacting residue.

PMID- 9512704
TI  - Stepwise selection of TetR variants recognizing tet operator 6C with high
      affinity and specificity.
AB  - The exchange of Trp43 to Arg in the sixth position of the TetR recognition alpha
      helix leads to a new DNA recognition specificity for tetO-6C, however, it is
      bound with only low affinity. Specificity and affinity of this mutant were
      substantially increased by additional amino acid exchanges in the last positions
      of the recognition alpha-helix and the turn, which most likely play structural
      roles in the formation of the TetR-tetO complex. The last residue in the turn of
      the alpha-helix-turn-alpha-helix motif is a discriminator of binding to other
      tetO variants and contributes efficiently to the affinity for the newly
      recognized tetO-6C sequence. Short residues at this position improve sequence
      specific binding when combined with a residue in the recognition alpha-helix,
      which directly reads out the recognized tetO sequence. We assume that small
      residues at the end of the turn permit the recognition alpha-helix to assume the
      optimal position within the motif for docking to the DNA target. Thus, residues
      allowing direct and favourable contacts to the newly recognized DNA are not
      sufficient to increase the binding specificity and affinity, but need to be
      accompanied by additional exchanges allowing the formation of these contacts.

PMID- 9512705
TI  - Staphylococcal alpha-hemolysin can form hexamers in phospholipid bilayers.
AB  - Atomic force microscopy (AFM) was used to study the structure of the
      staphylococcal alpha-hemolysin (alpha HL) oligomer formed in supported
      phospholipid bilayers. In contrast to the recent X-ray crystallographic
      demonstration of a heptameric stoichiometry for the oligomer formed in
      deoxycholate (DOC) micelles, the high-resolution unprocessed AFM images
      unequivocally revealed a hexamer in these phospholipid bilayers. Independent
      support of this hexameric stoichiometry was obtained from the measurements of the
      lattice constant in the AFM images and from gel electrophoresis. Therefore, alpha
      HL can form two different, energetically stable oligomers, which differ in at
      least stoichiometry but perhaps subunit structure as well. Furthermore, stable,
      incomplete oligomers were observed in the AFM images, which may be of relevance
      to the mechanism by which alpha HL damages the cell.

PMID- 9512706
TI  - Influence of an antiviral compound on the temperature dependence of viral protein
      flexibility and packing: a molecular dynamics study.
AB  - The antiviral activity of compounds that bind an internal pocket of
      picornaviruses is due in part to stabilization of the protein capsid and
      inhibition of the uncoating process required for virus replication. Information
      on the basis for this structural stabilization of the virus capsid is important
      to elucidate the mechanism of antiviral action and provide insights into the
      disassembly process. It has been proposed that this stabilization is entropically
      based, since binding the nonpolar antiviral compound increases the
      compressibility, and thus the conformational flexibility, of the virus. Such a
      proposal predicts a difference in the temperature dependence of the atomic
      positional fluctuations for free virus and drug-bound virus; nonpolar
      interactions are weaker and less directional, and would give rise to greater
      conformational disorder at low temperature. Further, the transition that has been
      observed in globular proteins to a state resembling a frozen liquid, in which the
      protein is considered "trapped" in potential energy wells, is predicted to occur
      at lower temperature when the antiviral compound is bound. Results described here
      from computer simulations of rhinovirus over a range in temperature show these
      predicted changes in conformational disorder and the temperature of the
      transition in mobility. In addition to providing independent support for the
      above proposal for antiviral activity, these results indicate that the mobility
      transition of a protein can be controlled by the binding of an appropriate
      ligand, an effect not previously reported.

PMID- 9512707
TI  - Molecular analysis of the regulation of csiD, a carbon starvation-inducible gene
      in Escherichia coli that is exclusively dependent on sigma s and requires
      activation by cAMP-CRP.
AB  - The general stress-induced sigma subunit sigma s of Escherichia coli RNA
      polymerase is closely related to the vegetative sigma factor sigma 70. In view of
      their very similar promoter specificity in vitro, it is unclear how sigma factor
      selectivity in the expression of sigma s-dependent genes is generated in vivo.
      The csiD gene is such a strongly sigma s-dependent gene. In contrast to sigma s,
      which is induced in response to many different stresses, csiD, whose expression
      is driven from a single promoter, is induced by carbon starvation only. To our
      knowledge, the csiD promoter is the first characterized promoter which is not
      only exclusively dependent on sigma s-containing RNA polymerase (E sigma s), but
      also requires an activator, cAMP-CRP. In addition, leucine-responsive regulatory
      protein (Lrp) acts as a positive modulator of csiD expression. Also in vitro, E
      sigma s is more efficient than E sigma 70 in csiD promoter binding, open complex
      formation and run-off transcription, which might be due to the poor match of the
      csiD -35 region to the sigma 70 consensus and to transcription by E sigma s being
      less dependent on contacts in this region. By DNase I protection experiments, a
      cAMP-CRP binding site centered at -68.5 nucleotides upstream of the csiD
      transcriptional start site was identified. While cAMP-CRP stimulates E sigma 70
      binding, it does not promote open complex formation by E sigma 70, but does so in
      conjunction with E sigma s. With linear templates, cAMP-CRP significantly
      stimulates E sigma s-mediated in vitro transcription, whereas transcription by E
      sigma 70 is negligible and hardly stimulated by cAMP-CRP. These findings may
      reflect different or less stringent positional requirements for an activator site
      for E sigma s than for E sigma 70, and indicate that cAMP-CRP contributes to
      sigma factor selectivity at the csiD promoter. In vitro transcription experiments
      with super-coiled templates, however, revealed significant cAMP-CRP-stimulated
      transcription also by E sigma 70. Yet, under these conditions, H-NS was found to
      restore E sigma s specificity by strongly interfering with cAMP-CRP/E sigma 70
      dependent transcription. Lrp strongly and cooperatively binds to multiple sites
      located between positions -14 and -102 (in a way that suggests DNA wrapping
      around multiple Lrp molecules) and moderately stimulates in vitro transcription,
      especially with E sigma s. In summary, we conclude that the csiD promoter has an
      intrinsic preference for E sigma s, but that also protein factors such as cAMP
      CRP, Lrp and probably H-NS as well as DNA conformation contribute to its strong E
      sigma s selectivity. Furthermore, this strong E sigma s preference in combination
      with a requirement for high concentrations of the essential activator cAMP-CRP
      ensures csiD expression under conditions of carbon starvation, but not other
      stress conditions.

PMID- 9512708
TI  - FruR-mediated transcriptional activation at the ppsA promoter of Escherichia
      coli.
AB  - The start site of transcription of the ppsA gene, whose expression is controlled
      by the regulatory protein FruR in Escherichia coli, was determined by primer
      extension of in vivo transcripts. The interactions of the ppsA promoter with
      either RNA polymerase or FruR factor were analysed by the base removal method.
      Our results indicate that: (i) the RNA polymerase binding site has a -10 extended
      module but lacks its -35 hexamer; (ii) FruR binds to a target DNA region centered
      around position -45.5 upstream of the ppsA gene. In addition, circular
      permutation analysis showed that, upon binding to its site, FruR induces a sharp
      bend of 120 degrees in the DNA helix, which suggests a crucial involvement of
      FruR-induced bending in ppsA promoter activation. Direct contacts between the
      upstream activating DNA and RNA polymerase were studied in an in vitro
      transcription assay by using reconstituted RNA polymerase mutants containing Ala
      substitutions in C-terminal domain of their alpha subunit. The alpha[L262A],
      alpha[R265A] and alpha[N268A] substitutions, which caused the most drastic
      reduction in the FruR-mediated activation of the ppsA promoter, had previously
      been shown to inhibit the upstream element-mediated activation at the rrnBP1
      promoter.

PMID- 9512709
TI  - High-affinity DNA binding by the C-terminal domain of the transcriptional
      coactivator PC4 requires simultaneous interaction with two opposing unpaired
      strands and results in helix destabilization.
AB  - The general transcriptional cofactor PC4 enhances transcription from various
      promoters and functions with a wide range of transcriptional activators. Earlier
      studies have suggested that this enhancement originates mostly from stabilization
      of the TATA-box/TFIID/TFIIA complex by simultaneous interaction of PC4 with
      transactivation domains of upstream-binding factors and the basal factor TFIIA.
      However, the C-terminal half of the protein also has been shown to exhibit
      substantial ssDNA binding properties, to which as yet no clear function has been
      assigned. We have investigated the interaction of this domain with various DNA
      structures and report that high-affinity binding, characterized by an equilibrium
      dissociation constant in the nanomolar range, requires either a heteroduplex
      containing a minimum of about eight mismatches, or alternatively a single
      stranded DNA molecule consisting of 16 to 20 nucleotides. Furthermore, both
      juxtaposed single strands of a heteroduplex are protected by the C-terminal
      domain of PC4 in DNase I footprinting experiments, whereas the double-stranded
      regions do not appear to be contacted. We conclude from these observations that
      the role of PC4 ssDNA binding is likely to involve simultaneous interaction with
      opposing strands in internally melted duplexes, or the induction of a pronounced
      distortion in the local structure of ssDNA that results in a similar juxtaposed
      arrangement of single strands. In addition, we have observed that both the PC4 C
      terminal domain and the intact PC4 destabilize dsDNA and we discuss the possible
      involvement of PC4 in promoter opening and other strand displacement events.

PMID- 9512710
TI  - Distinct functions of N and C-terminal domains of GreA, an Escherichia coli
      transcript cleavage factor.
AB  - The prokaryotic transcription factors GreA and GreB are involved in the
      regulation of transcript elongation by RNA polymerase (RNAP). Their known
      activities include suppression of transcription arrest, enhancement of
      transcription fidelity, and facilitation of the transition from abortive
      initiation to productive elongation. Presumably, Gre proteins exert their
      functions by altering the conformation of the enzyme in ternary elongation
      complexes (TEC) and inducing the cleavage of nascent RNA. GreA and GreB have a
      similar structural organization and consist of two domains: a C-terminal globular
      and an extended N-terminal coiled-coil domain. To investigate the functional
      roles of Gre domains, we expressed separately the N and C-terminal domains of
      GreA (NTD and CTD, respectively) and characterized their activities with in vitro
      assays. We demonstrate that the NTD possesses the residual transcript cleavage
      activity of the wild-type GreA. The CTD does not display any nucleolytic
      activity; however, it substantially increases the cleavage activity of the NTD.
      In contrast to NTD, the CTD competes with GreA and GreB for binding to RNAP and
      inhibits their transcript cleavage and antiarrest activities. Both domains
      individually and together inhibit transcription elongation. From these results we
      conclude that the NTD is responsible for the GreA induction of nucleolytic
      activity while the CTD determines the binding of GreA to RNAP. Both domains are
      required for full functional activity of GreA.

PMID- 9512711
TI  - The antibiotic thiostrepton inhibits a functional transition within protein L11
      at the ribosomal GTPase centre.
AB  - A newly identified class of highly thiostrepton-resistant mutants of the archaeon
      Halobacterium halobium carry a missense mutation at codon 18 within the gene
      encoding ribosomal protein L11. In the mutant proteins, a proline, conserved in
      archaea and bacteria, is converted to either serine or threonine. The mutations
      do not impair either the assembly of the mutant L11 into 70 S ribosomes in vivo
      or the binding of thiostrepton to ribosomes in vitro. Moreover, the corresponding
      mutations at proline 22, in a fusion protein of L11 from Escherichia coli with
      glutathione-S-transferase, did not reduce the binding affinities of the mutated
      L11 fusion proteins for rRNA of of thiostrepton for the mutant L11-rRNA complexes
      at rRNA concentrations lower than those prevailing in vivo. Probing the structure
      of the fusion protein of wild-type L11, from E. coli, using a recently developed
      protein footprinting technique, demonstrated that a general tightening of the C
      terminal domain occurred on rRNA binding, while thiostrepton produced a footprint
      centred on tyrosine 62 at the junction of the N and C-terminal domains of protein
      L11 complexed to rRNA. The intensity of this protein footprint was strongly
      reduced for the mutant L11-rRNA complexes. These results indicate that although,
      as shown earlier, thiostrepton binds primarily to 23 S rRNA, the drug probably
      inhibits peptide elongation by impeding a conformational change within protein
      L11 that is important for the function of the ribosomal GTPase centre. This
      putative inhibitory mechanism of thiostrepton is critically dependent on proline
      18/22. Moreover, the absence of this proline from eukaryotic protein L11
      sequences would account for the high thiostrepton resistance of eukaryotic
      ribosomes.

PMID- 9512712
TI  - Differential cleavage of LexA and UmuD mediated by recA Pro67 mutants:
      implications for common LexA and UmuD binding sites on RecA.
AB  - In Escherichia coli, RecA-mediated cleavage of LexA repressor is a key regulatory
      event required for expression of SOS genes involved in the repair of DNA damage.
      RecA also mediates the cleavage of UmuD protein to UmuD, a form active in SOS
      mutagenesis. To determine whether LexA and UmuD have common binding determinants
      on RecA, we have compared the ability of several recA mutants to function in the
      cleavage of LexA versus UmuD in vivo. The data reveal that while some recA
      mutations at Pro67 have a similar effect on LexA and UmuD cleavage, others have
      striking differential effects. For example, a Pro67-->Trp mutation results in a
      high level of constitutive cleavage of both proteins. However, Pro67-->Asp and
      Glu mutations promote constitutive cleavage of LexA and reduce induction of UmuD
      cleavage to just 5 to 10% of wild-type activity. In contrast, Pro67-->Arg
      prevents LexA cleavage while allowing nearly 50% of wild-type induction of UmuD
      cleavage. These results are consistent with the idea that Pro67 is located at a
      site in the nucleoprotein filament where both LexA and UmuD contact RecA.

PMID- 9512714
TI  - Rice non-specific lipid transfer protein: the 1.6 A crystal structure in the
      unliganded state reveals a small hydrophobic cavity.
AB  - This study describes the high-resolution X-ray structure of the non-specific
      lipid transfer protein (ns-LTP) from rice seeds in the unliganded state. The
      model has been refined to a crystallographic R-factor of 0.186 for 8.0 to 1.6 A
      data (with Fo > 2 sigma F). It accounts for all 91 amino acid residues, 68 water
      molecules, one sulfate ion, and two molecules of 3-[cyclohexylamino]-1
      propanesulfonic acid. The root-mean-square deviations from ideal bond lengths and
      angles are 0.017 A and 1.76 degrees, respectively. The overall fold of rice ns
      LTP is very similar to that of maize ns-LTP. A superposition of 91 common C alpha
      atoms in rice and maize ns-LTPs, both in the unliganded state, gives a root-mean
      square deviation of 1.2 A. Large structural differences from the crystal
      structure of maize ns-LTP are observed in two regions: the loop between two alpha
      helices H1 and H2, where one residue deletion (Gln21 of maize sequence) occurs,
      and the C-terminal region around Tyr79. The C-terminal region of rice protein is
      somewhat collapsed into the hydrophobic cavity. As a consequence, its hydrophobic
      cavity is considerably smaller than that of maize protein (144 A3 versus 408 A3
      for van der Waals cavity volumes), despite a high level of sequence identity
      (79%) between them. In the rice ns-LTP structure, the side-chain of Arg44
      partially blocks the mouth of the cavity, while the side-chain of Ile81
      effectively closes the other end by protruding into the cavity. And the side
      chain of Tyr79 divides the cavity into two parts, with the larger part being
      shielded from the solvent. The present study illuminates the structure-function
      relationship of rice ns-LTP and allows a detailed structural comparison with
      other plant ns-LTPs.

PMID- 9512713
TI  - Who checks the checkers? Four validation tools applied to eight atomic resolution
      structures. EU 3-D Validation Network.
AB  - Eight protein crystal structures, which have been refined against X-ray
      diffraction data extending to atomic resolution, 1.2 A or better, were inspected
      using four different validation tools, PROCHECK, PROVE, SQUID and WHATCHECK. Two
      general questions were addressed. (1) Do the structures imply changes in
      "expected" stereochemical properties and are the target values used for
      restraints in the validation programs and the refinement protocol appropriate?
      (2) Can errors in models be detected and how reliable are the coordinates after
      refinement? Preliminary analysis by members of the network led to modifications
      both to the validation programs and to the refinement protocols. The results of
      the final analyses are reported here. Apparent discrepancies in cell dimensions
      were identified. Most stereochemical properties are shown to be more tightly
      clustered than for lower resolution analyses. In contrast the omega angle has a
      wider distribution. The validation software is generally available and can be
      accessed at servers listed at the end of the paper.

PMID- 9512715
TI  - The 2.3 A X-ray crystal structure of S. cerevisiae phosphoglycerate mutase.
AB  - The high resolution crystal structure of Saccharomyces cerevisiae
      phosphoglycerate mutase has been determined. This structure shows important
      differences from the lower resolution structure deposited in 1982. The crystal
      used to determine the new structure was of a different form, having spacegroup
      P2(1). The model was refined to a crystallographic R-factor of 18.9% and a free R
      factor of 28.4% using all data between 25 and 2.3 A and employing a bulk solvent
      correction. The enzyme is a tetramer of identical, 246 amino acid subunits, whose
      structure is revealed to be a dimer of dimers, with four independent active sites
      located well away from the subunit contacts. Each subunit contains two domains,
      the larger with a typical nucleotide binding fold, although phosphoglycerate
      mutase has no physiological requirement to bind nucleotides. The catalytic-site
      histidine residues are no longer in a "clapping-hands" conformation, but more
      resemble the conformation seen in the distantly related enzymes prostatic acid
      phosphatase and fructose-2,6-bisphosphatase. However, the catalytic histidine
      residues in the mutase are found to be much closer to each other than in the
      phosphatase structures, perhaps due to the absence of bound ligands in the mutase
      crystal. An intricate web of H-bonds is found around the catalytic histidine
      residues, high-lighting residues probably important for maintaining their correct
      orientation and charge. The positions of certain other residues, including some
      found near the catalytic site and some lining the catalytic-site cleft, have been
      changed by the correction of registration errors between sequence and electron
      density in the original structure. Electron density was apparent for a portion of
      the functionally important C-terminal tail, which was absent from the earlier
      structure, showing it to adopt a mainly helical conformation.

PMID- 9512716
TI  - Solution structure of the C-terminal SH2 domain of the p85 alpha regulatory
      subunit of phosphoinositide 3-kinase.
AB  - Heterodimeric class IA phosphoinositide 3-kinase (PI 3-kinase) plays a crucial
      role in a variety of cellular signalling events downstream of a number of cell
      surface receptor tyrosine kinases. Activation of the enzyme is effected in part
      by the binding of two Src homology-2 domains (SH2) of the 85 kDa regulatory
      subunit to specific phosphotyrosine-containing peptide motifs within activated
      cytoplasmic receptor domains. The solution structure of the uncomplexed C
      terminal SH2 (C-SH2) domain of the p85 alpha subunit of PI 3-kinase has been
      determined by means of multinuclear, double and triple-resonance NMR experiments
      and restrained molecular-dynamics simulated-annealing calculations. The solution
      structure clearly indicates that the uncomplexed C-SH2 domain conforms to the
      consensus polypeptide fold exhibited by other SH2 domains, with an additional
      short helical element at the N terminus. In particular, the C-SH2 structure is
      very similar to both the p85 alpha N-terminal SH2 domain (N-SH2) and the Src SH2
      domain with a root mean square difference (rmsd) for 44 C alpha atoms of 1.09 and
      0.89 A, respectively. The canonical BC, EF and BG loops are less well-defined by
      the experimental restraints and show greater variability in the ensemble of C-SH2
      conformers. The lower level of definition in these regions may reflect the
      presence of conformational disorder, an interpretation supported by the absence
      or broadening of backbone and side-chain NMR resonances for some of these
      residues. NMR experiments were performed, where C-SH2 was titrated with
      phosphotyrosine-containing peptides corresponding to p85 alpha recognition sites
      in the cytoplasmic domain of the platelet-derived growth-factor receptor. The
      ligand-induced chemical-shift perturbations indicate the amino-acid residues in C
      SH2 involved in peptide recognition follow the pattern predicted from homologous
      complexes. A series of C-SH2 mutants was generated and tested for phosphotyrosine
      peptide binding by surface plasmon resonance. Mutation of the invariant Arg36
      (beta B5) to Met completely abolishes phosphopeptide binding. Mutation of each of
      Ser38, Ser39 or Lys40 in the BC loop to Ala reduces the affinity of C-SH2 for a
      cognate phosphopeptide, as does mutation of His93 (BG5) to Asn. These effects are
      consistent with the involvement of the BC loop and BG loops regions in ligation
      of phosphopeptide ligands. Mutation of Cys57 (beta D5) in C-SH2 to Ile, the
      corresponding residue type in the p85 alpha N-SH2 domain, results in a change in
      peptide binding selectivity of C-SH2 towards that demonstrated by p85 alpha N
      SH2. This pattern of p85 alpha phosphopeptide binding specificity is interpreted
      in terms of a model of the p85 alpha/PDGF-receptor interaction.

PMID- 9512717
TI  - Cooperative folding of a protein mini domain: the peripheral subunit-binding
      domain of the pyruvate dehydrogenase multienzyme complex.
AB  - The peripheral subunit-binding domain from the dihydrolipoamide acetyltransferase
      (E2) component of the pyruvate dehydrogenase multienzyme complex from Bacillus
      stearothermophilus is stably folded, despite its short sequence of only 43 amino
      acid residues. A 41 residue peptide derived from this domain, psbd41, undergoes a
      cooperative thermal unfolding transition with a tm of 54 degrees C. This three
      helix protein is monomeric as judged by ultracentrifugation and concentration
      dependent CD measurements. Peptides corresponding to the individual helices are
      largely unstructured both alone and in combination, indicating that the unusual
      stability of this protein does not arise solely from unusually stable alpha
      helices. Chemical denaturation by guanidine hydrochloride is also cooperative
      with a delta GH2O of 3.1 kcal mol-1 at pH 8.0 and 25 degrees C. The chemical
      denaturation is broad with an m-value of 760 cal mol-1 M-1. psbd41 contains a
      buried aspartate residue at position 34 that may provide stability and
      specificity to the fold. A mutant peptide, psbd41Asn was synthesized in which the
      buried aspartate residue was mutated to asparagine. This peptide still folds
      cooperatively and it is monomeric, but is much less thermostable than the wild
      type with a tm of only 31 degrees C. Chemical denaturations at 4 degrees C give
      an m-value of 740 cal mol-1 M-1, similar to the wild-type, but the stability
      delta GH2O is only 1.4 kcal mol-1. Both the wild-type and the mutant unfold at
      extremes of pH, but at 4 degrees C psbd41Asn is folded over a narrower pH range
      than the wild-type. Although the mutant unfolds cooperatively by thermal and by
      chemical denaturation, its NMR spectrum is significantly broader than that of the
      wild-type and it binds ANS. These results show that Asp34 is vital for the
      stability and specificity of this structure, the second smallest natural sequence
      known to fold in the absence of disulfide bonds or metal or ligand-binding sites.

PMID- 9512718
TI  - Two forms of the pH 4 folding intermediate of apomyoglobin.
AB  - The pH 4 folding intermediate of apomyoglobin exists in two forms (Ia, Ib) at
      equilibrium. Their ratio depends on pH, urea concentration and the presence or
      absence of a stabilizing anion (citrate, sulfate), and it does not depend on
      protein concentration. The Ia and Ib species are separated by a kinetic barrier
      and their interconversion can be monitored by tryptophan fluorescence in stopped
      flow experiments. At pH 4.2, Ib is converted to Ia at low urea concentrations and
      urea unfolding gives the unfolding transition of Ia. During the refolding of
      native (N) apomyoglobin at pH 6, starting from the acid unfolded species (U),
      both Ia and Ib appear as transient intermediates and both Ia and Ib appear as
      transient intermediates in the acid-induced unfolding of N. The results are
      consistent with a linear folding and unfolding pathway: U reversible Ia
      reversible Ib reversible N. Apomyoglobin provides the opportunity to investigate
      at equilibrium the structures and properties of two different kinetic folding
      intermediates. A non-obligatory dimeric species of the pH 4 intermediate is
      formed slowly and contributes to the refolding kinetics at concentrations above 5
      microM. The dimer dissociates slowly and during refolding at pH 6 it forms N in a
      later time range than does the monomer.

PMID- 9512719
TI  - Thermodynamic stability and folding of GroEL minichaperones.
AB  - The apical domain of GroEL (residues 191 to 376) and its C-terminally truncated
      fragment GroEL(191-345) are expressed with high yield in Escherichia coli to give
      functional monomeric minichaperones. Owing to the reversible folding behaviour of
      the minichaperones we can analyse the folding of the polypeptide binding domain
      of the multidomain GroEL protein, the folding of which is known to be
      irreversible. The apical domain shows two reversible temperature transitions with
      transition midpoints at 35 degrees C and at 67 degrees C that can be attributed
      to the unfolding of the C-terminal helices and the domain core, respectively. The
      native state of the domain core is stabilized by 5.5 kcal mol-1 relative to the
      unfolded state. The rate constant of folding of the apical domain core is
      independent of the minichaperone concentration and the presence of the C-terminal
      alpha-helices. A folding intermediate on the folding pathway is destabilized
      relative to the native state by 1.6 kcal mol-1, which is also detected by
      equilibrium and kinetic binding of the dye bis-ANS. Reversible folding of the
      polypeptide domain of GroEL guarantees highly efficient chaperonin activity
      within the GroEL toroid.

PMID- 9512720
TI  - Adaptation of protein surfaces to subcellular location.
AB  - In vivo, proteins occur in widely different physio-chemical environments, and,
      from in vitro studies, we know that protein structure can be very sensitive to
      environment. However, theoretical studies of protein structure have tended to
      ignore this complexity. In this paper, we have approached this problem by
      grouping proteins by their subcellular location and looking at structural
      properties that are characteristic to each location. We hypothesize that,
      throughout evolution, each subcellular location has maintained a characteristic
      physio-chemical environment, and that proteins in each location have adapted to
      these environments. If so, we would expect that protein structures from different
      locations will show characteristic differences, particularly at the surface,
      which is directly exposed to the environment. To test this hypothesis, we have
      examined all eukaryotic proteins with known three-dimensional structure and for
      which the subcellular location is known to be either nuclear, cytoplasmic, or
      extracellular. In agreement with previous studies, we find that the total amino
      acid composition carries a signal that identifies the subcellular location. This
      signal was due almost entirely to the surface residues. The surface residue
      signal was often strong enough to accurately predict subcellular location, given
      only a knowledge of which residues are at the protein surface. The results
      suggest how the accuracy of prediction of location from sequence can be improved.
      We concluded that protein surfaces show adaptation to their subcellular location.
      The nature of these adaptations suggests several principles that proteins may
      have used in adapting to particular physio-chemical environments; these
      principles may be useful for protein design.

PMID- 9512721
TI  - Evaluation and modification of a physiologically based model of lead kinetics
      using data from a sequential isotope study in cynomolgus monkeys.
AB  - Endogenous (predominantly bone) and exogenous lead were differentially labeled in
      two 11-year-old female cynomolgus monkeys (Macaca fascicularis) to establish the
      contributions of the two sources to blood lead. The monkeys had been administered
      a common lead isotope "mix" at the rate of about 1300 micrograms Pb/kg body
      wt/day from age 10 months until the start of the study. On day 0, common lead was
      replaced in sequence by mixes artificially enriched in 204Pb, 206Pb, and 207Pb,
      given for periods of from 50 to 281 days. Total lead ingestion rate was held
      constant except during administration of the 207Pb-enriched mix to one of the
      monkeys, when it was reduced to 650 micrograms/kg/day. Blood and bone were
      sampled at intervals and analyzed for their content of each of the isotope mixes.
      A physiologically based model of human lead kinetics was scaled to the cynomolgus
      monkey and fit to the data to test the correctness of the model structure and to
      assist with interpretation of study results. Fractional absorption was varied to
      achieve the best visual fits of the scaled model to blood and bone concentration
      data for each monkey. The model failed to reproduce the sharp drop in isotope
      concentrations in blood observed after each exchange of isotope mix.
      Consequently, it was revised to include a rapid-turnover trabecular bone
      compartment and a slow-turnover cortical bone compartment, using estimates of
      trabecular and cortical bone turnover rates from histomorphometric studies in
      adult cynomolgus monkeys. The revised model fit most of the sets of bone and
      blood concentrations well. About 17% of the blood lead originated from bone after
      11 years of exposure, at blood lead concentrations in excess of 50 micrograms/dl.
      The rate of return of common lead from bone, as estimated from the model, was 28
      micrograms/day just before termination of controlled common lead exposure on day
      0. Based on the success of the scaled human model in fitting these data and on
      the absolute and relative values of bone and blood lead concentrations, the
      metabolism of lead in the cynomolgus monkey appears to be similar to human lead
      metabolism.

PMID- 9512722
TI  - A comparison of the individual and collective effects of four glucosinolate
      breakdown products from brussels sprouts on induction of detoxification enzymes.
AB  - Four glucosinolate derivatives were evaluated individually and as a mixture for
      their effects on hepatic P4501A (CYP1A), glutathione S-transferase (GST), quinone
      reductase (QR), glutathione reductase (G-Rd), and GSH levels. Doses of the
      derivatives were chosen to represent their relative abundance in Brussels
      sprouts. Adult male F344 rats received either corn oil (vehicle); one of the
      agents: indole-3-carbinol (I3C, 56 mg/kg), iberin (38 mg/kg),
      phenylethylisothiocyanate (PEITC, 0.1 mg/kg), or cyanohydroxybutene (crambene, 50
      mg/kg); or all of the agents at the doses shown (as a mixture) given by gavage
      daily for 7 days. The mixture and I3C caused an 11- and 9.4-fold induction of
      CYP1A, respectively. Crambene and I3C each caused a 1.4-fold increase in GST,
      while the mixture caused a 2.5-fold increase. Crambene and I3C caused a 2.5- and
      1.9-fold increase in QR, respectively. The mixture caused a 6.2-fold increase.
      Crambene, PEITC, and the mixture caused a 1.8-, 1.6-, and 2.0-fold increase in
      hepatic GSH levels, respectively. Crambene, I3C, iberin, and the mixture caused
      1.3-, 1.4-, 1.2-, and 1.7-fold increases in G-Rd, respectively. In a second study
      the mixture was given at 60 and 20% of the original dose. CYP 1A, QR, G-Rd, and
      GST elevations were dose-dependent; GSH levels were not elevated. It is concluded
      that I3C and crambene are responsible for the majority of enzyme increases seen.
      A synergistic effect of I3C and crambene was evident on induction of GST and QR,
      but not on GSH, G-Rd, or P4501A.

PMID- 9512723
TI  - Metallothionein (MT)-null mice are sensitive to cisplatin-induced hepatotoxicity.
AB  - cis-Diamminedichloroplatinum (cisplatin) is an important anticancer drug used to
      treat solid tumors. The nephrotoxicity of cisplatin is recognized as the most
      important dose-limiting factor, but high doses of cisplatin also produce
      hepatotoxicity. However, little is known about cisplatin-induced liver injury and
      the role of metallothionein, a cysteine-rich, metal-binding protein, in
      modulating its hepatotoxicity. This study was designed to examine cisplatin
      hepatotoxicity in control and metallothionein-I/II knockout (MT-null) mice.
      Animals were given a single injection of cisplatin (50-200 mumol/kg i.p.), and
      liver injury was evaluated 3-16 h later. Cisplatin produced dose- and time
      dependent liver injury, as evidenced by increased serum activity of alanine
      aminotransferase (ALT), as well as by histopathology. Apoptosis, rather than
      necrosis, predominates in cisplatin-induced liver injury, as indicated by
      increased numbers of apoptotic cells (hematoxylin and eosin staining), in situ
      apoptotic DNA detection, and DNA fragmentation on agarose gel electrophoresis. MT
      null mice were more sensitive than controls to cisplatin-induced hepatotoxicity.
      Cisplatin (200 mumol/kg) was lethal to 12% of control mice, but 60% of MT-null
      mice died within 16 h. At the dose of 150 mumol/kg, serum ALT activities were
      increased 2-fold in control mice compared to 6.5-fold in MT-null mice. Apoptotic
      lesions were more pronounced in MT-null than in control mice. MT-null mice were
      also more susceptible than controls to cisplatin-induced nephrotoxicity, as
      evidenced by having higher blood urea nitrogen concentrations. Furthermore,
      cultured MT-null hepatocytes were more sensitive than control cells to the
      cytotoxicity of cisplatin (50-200 microM), as indicated by lactate dehydrogenase
      leakage into the medium. These results demonstrate that (1) high doses of
      cisplatin produce hepatotoxicity, with apoptosis as the major lesion, and (2) MT
      protects against cisplatin-induced liver injury.

PMID- 9512724
TI  - 2-sec-butyl-4,5-dihydrothiazole is a ligand for mouse urinary protein and rat
      alpha 2u-globulin: physiological and toxicological relevance.
AB  - Mouse urinary protein (MUP) and alpha 2u-globulin are structurally homologous
      proteins that belong to a superfamily of ligand-binding proteins and represent
      the major urinary proteins excreted by adult male mice and rats, respectively.
      Although a variety of xenobiotics bind to alpha 2u-globulin and produce a male
      rat-specific hyaline droplet nephropathy, no endogenous ligand for this protein
      has been identified. Despite extensive sequence homology. MUP does not bind to
      hyaline droplet-inducing agents. While performing experiments with purified MUP,
      we observed that it presented with a strong, distinctive odor reminiscent of
      mouse urine. To determine whether this odor was the result of contamination or
      degradation or was attributed to an endogenous ligand bound to the protein, the
      protein was subjected to thermal desorption and any released volatile compounds
      were detected with a gas chromatograph equipped with an external sniff port and
      mass spectrometer. With this approach, two odorous compounds were detected at the
      sniff port by a human observer, but only one was present in sufficient mass to
      allow identification. This compound, which presented with the characteristic
      odor, was subsequently identified as 2-sec butyl-4,5-dihydrothiazole (DHT) by
      GC/MS/matrix isolation IR and NMR analyses. The identification of DHT was
      confirmed by comparing the chromatographic and spectral properties to those of
      the synthesized authentic compound. In direct contrast, purified urinary alpha 2u
      globulin did not present with an obvious odor, and no volatile ligands were
      detected on this protein. Although DHT is a major endogenous ligand for MUP, it
      was also found to competitively inhibit the binding of [14C]d-limonene-1,2
      epoxide to alpha 2u-globulin with relatively high affinity (Ki = 2.3 microM).
      When dosed orally to F344 rats, DHT (1 mmol/kg for 3 days) caused the
      characteristic exacerbation of hyaline droplets in male rat kidneys and increased
      renal levels of immunoreactive alpha 2u-globulin about threefold over control
      levels. These results indicate that despite structural homology, MUP and alpha 2u
      globulin are distinguished by the presence of a volatile endogenous ligand only
      on the former, a distinction that may reflect differences in the physiological
      functions of the two proteins. Furthermore, although DHT can bind to both MUP and
      alpha 2u-globulin, renal toxicity was only observed in rats, thereby emphasizing
      the unique toxicological properties of alpha 2u-globulin in the development of
      hyaline droplet nephropathy.

PMID- 9512725
TI  - Pharmacodynamic responses of F344 rats to the mouse hepatocarcinogen oxazepam in
      a 90-day feed study.
AB  - Oxazepam (Serax) is a widely used benzodiazepine anxiolytic agent and a
      metabolite of other benzodiazepines such as Valium and Librium. Chronic feeding
      studies indicated that oxazepam is an hepatocarcinogen in B6C3F1 mice but did not
      increase hepatic tumors in F344 rats. The present study was performed to compare
      the hepatic responses of rats with our previous findings in mice to explore the
      reason(s) for the dramatic differences in tumor response between the two species.
      Male F344 rats (10 per dose-time group) received diets containing oxazepam at 0,
      25, 125, 2500, and 5000 ppm. Hepatocyte labeling indices were measured
      immunohistochemically by PCNA and BrDU during the last 7 days before sacrifices
      after 15, 30, 45, and 90 days of dosing. Serum oxazepam was determined by reverse
      phase HPLC. Results indicated that oxazepam induced significant liver weight
      increases in a dose-related fashion by 15 days, which remained elevated for the
      entire study. No important clinical chemistry or pathology changes were noted
      except those related to hypertrophy. Cell proliferation was significantly
      increased in a dose-related manner by the 15- and 30-day timepoint in the 2500
      and 5000 ppm groups. The most significant finding in the present study of
      oxazepam was plasma levels of the parent compound. Plasma levels in rats were
      dramatically lower than in B6C3F1 mice exposed to oxazepam in studies conducted
      earlier at the same dose levels. These results suggest that the early responses
      of rats and mice to oxazepam, such as cell proliferation and clinical chemistry
      parameters, are similar. Our previous studies demonstrated that oxazepam
      metabolites are excreted in the urine of rats, similar to humans, whereas mice
      excrete oxazepam metabolites in bile allowing enterohepatic recirculation, which
      results in high plasma levels of oxazepam. These data indicate that the rat
      excretes oxazepam kinetically (rate and route) similar to humans, but the mouse
      produces metabolites similar to humans.

PMID- 9512726
TI  - Cadmium decreases SGLT1 messenger RNA in mouse kidney cells.
AB  - Mouse renal cortical tubule cells in primary culture exposed to cadmium (Cd2+)
      develop decreased Na(+)-glucose cotransport activity as measured by uptake of the
      glucose analogue alpha-methyl-glucoside. RNA was isolated from kidney cell
      cultures, and after reversed transcription, the DNA was amplified with primers to
      rat SGLT1 (the high affinity isoform of the sodium glucose cotransporter) and
      mouse beta-actin. Only one product was identified after amplification with the
      rat SGLT1 primers, which on sequencing was 96% identical to rat SGLT1. Compared
      to beta-actin, the intensity of the SGLT1 message declined progressively as CdCl2
      concentration in the medium increased from 0 to 10 microM. Similar decreases in
      SGLT1 mRNA were also observed as media zinc (Zn2+) concentrations rose from 0 to
      75 microM or as copper (Cu) concentrations increased from 0 to 150 microM.
      Exposure to 8 microM Cd as Cd-metallothionein (Cd7-MT) also caused a fall in
      relative SGLT1 mRNA abundance, and at nearly identical internal Cd concentrations
      of 40-43 pmol/microgram DNA, both Cd7-MT and CdCl2 reduced SGLT1 mRNA to 33% of
      control. In general, the fall in SGLT1 mRNA was more rapid than the decline in
      Na(+)-dependent glucose uptake after cells were exposed to Cd2+. These findings
      suggest that the effects of Cd2+ and other metals on renal glucose transport are
      related to decreased expression of SGLT1 message.

PMID- 9512727
TI  - Comparative toxicity of eugenol and its quinone methide metabolite in cultured
      liver cells using kinetic fluorescence bioassays.
AB  - Comparative kinetic analyses of the mechanisms of toxicity of the alkylphenol
      eugenol and its putative toxic metabolite (quinone methide, EQM) were carried out
      in cultured rat liver cells (Clone 9, ATCC) using a variety of vital fluorescence
      bioassays with a Meridian Ultima laser cytometer. Parameters monitored included
      intracellular GSH and calcium levels ([Ca2+]i), mitochondrial and plasma membrane
      potentials (MMP and PMP), intracellular pH, reactive oxygen species (ROS)
      generation, and gap junction-mediated intercellular communication (GJIC). Cells
      were exposed to various concentrations of test compounds (1 to 1000 microM) and
      all parameters monitored directly after addition at 15 s intervals for at least
      10 min. Eugenol depleted intracellular GSH, inhibited GJIC and generation of ROS,
      and had a modest effect on MMP at concentrations of 10 to 100 microM. At high
      concentrations (1000 microM), eugenol also affected [Ca2+]i, PMP, and pH. Effects
      of EQM were seen at lower concentrations (1 to 10 microM). The earliest and most
      potent effects of either eugenol or EQM were seen on GSH levels and GJIC.
      Coadministration of glutathione ethyl ester enhanced intracellular GSH levels by
      almost 100% and completely protected cells from cell death caused by eugenol and
      EQM. These results suggest that eugenol mediates its hepatotoxic effects
      primarily through depletion of cytoprotective thiols and interference in thiol
      dependent processes such as GJIC. Furthermore, our results support the hypothesis
      that the toxic effects of eugenol are mediated through its quinone methide
      metabolite.

PMID- 9512729
TI  - Comparison of the skin tumor-promoting potential of different organic peroxides
      in SENCAR mice.
AB  - The skin tumor-promoting activities of three organic peroxides were evaluated and
      compared to the activity of benzoyl peroxide, a well-characterized tumor
      promoter. Two of the compounds (di-t-butyl peroxide and dicumyl peroxide) were
      dialkyl peroxides and the other (di-m-chlorobenzoyl peroxide) was a diacyl
      peroxide. These compounds were selected based on a previous study in which we
      evaluated their capacity to induce epidermal hyperplasia, ornithine decarboxylase
      activity, and dark basal keratinocytes, which have been reliable short-term
      markers of tumor promotion. Dicumyl peroxide was a weak tumor promoter despite
      its high activity in inducing hyperplasia. Like benzoyl peroxide, di-m
      chlorobenzoyl peroxide generally had intermediate activity as an inducer of short
      term markers of tumor promotion and was a moderately effective tumor promoter.
      However, compared to benzoyl peroxide, di-m-chlorobenzoyl peroxide was more toxic
      to the skin, which may have limited its tumor-promoting activity. The final
      compound, di-t-butyl peroxide, which was essentially inactive in short-term
      assays, was also totally inactive in promoting papillomas or carcinomas in
      initiated skin. Tumor-promoting efficacy generally showed an inverse association
      with thermal stability for the compounds tested, suggesting that the rate of
      formation of free radicals is a key factor contributing to tumor promotion by
      organic peroxides. However, a number of other factors can potentially affect the
      activity of different organic peroxides as tumor promoters. Each compound
      evaluated had a different spectrum of activities, and these compounds should be
      useful for studying mechanisms of organic peroxide-induced tumor promotion.

PMID- 9512728
TI  - Induction of peroxisomal oxidases in mussels: comparison of effects of lubricant
      oil and benzo(a)pyrene with two typical peroxisome proliferators on peroxisome
      structure and function in Mytilus galloprovincialis.
AB  - Marine mussels are used as bioindicators of water pollution in marine and
      estuarine environments in the so-called "Mussel Watch" programs because of their
      capacity to accumulate numerous organic xenobiotics including aromatic
      hydrocarbons. In this study, we have analyzed the effects of two xenobiotics
      [benzo(a)pyrene and the water accommodated fraction of a lubricant oil] and two
      typical (rodent) peroxisome proliferators (clofibrate and dioctyl phthalate) on
      structure and function of peroxisomes in digestive glands of mussels Mytilus
      galloprovincialis, either following water exposure (for 1, 7, and 21 days) or
      after direct injection through the adductor muscle (for 1 and 7 days). The
      activities of catalase (CAT), acyl-CoA oxidase (AOX), and D-amino acid oxidase
      were determined in whole homogenates of digestive glands. In addition,
      stereological methods were applied on sections stained histochemically for
      demonstration of catalase activity in order to quantify the morphological changes
      of peroxisomes. The peroxisomal acyl-CoA oxidase and D-amino acid oxidase were
      increased in mussels injected for 7 days with benzo(a)pyrene, phthalate, and
      clofibrate and a similar trend was noted for benzo(a)pyrene and lubricant oil in
      water exposure experiments (21 days). The catalase activity was reduced or
      unchanged depending on the mode of exposure of animals. By stereology,
      significant increases of numerical and volume densities of peroxisomes were found
      in animals injected for 7 days with lubricant oil or clofibrate. These
      observations indicate that peroxisomal oxidases in mussels are induced at
      moderate rates in response to different xenobiotics and that their determination
      could provide a (sensitive) marker for detection of effects of some toxic
      pollutants, particularly the lubricant oils which in addition induce significant
      structural alterations of mussel peroxisomes.

PMID- 9512730
TI  - Alterations in human B cell calcium homeostasis by polycyclic aromatic
      hydrocarbons: possible associations with cytochrome P450 metabolism and increased
      protein tyrosine phosphorylation.
AB  - Previous studies performed in this laboratory have shown that certain
      benzo(a)pyrene (BaP) metabolites, such as benzo(a)pyrene-7,8-dihydrodiol (BaP-7,8
      diol) and benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE), were more effective
      in elevating intracellular Ca2+ in normal human peripheral blood mononuclear cell
      (HPBMC) T and B cells than was BaP. Additionally, it has been shown that the
      suppression of human T cell mitogenesis produced by polycyclic aromatic
      hydrocarbons (PAHs) and certain BaP metabolites is reversed by treatment with
      alpha-naphthoflavone (ANF), a cytochrome P450 1A and 1B inhibitor. ANF also
      diminishes the elevation in intracellular calcium (Ca2+) produced by BaP in
      HPBMC. In the present studies, we further defined the relationships between
      intracellular Ca2+ elevation produced by BaP and two immunotoxic P450-derived
      metabolites, BaP-7,8-diol and BPDE in the Daudi human B cell line. At 1, 4, and
      18 h, both BaP-7,8-diol and BPDE produced a significant rise in intracellular
      Ca2+. This effect, however, was not observed with BaP or benzo(e)pyrene (BeP), a
      nonimmunotoxic PAH. To evaluate the potential role of cytochrome P450 metabolism
      in PAH-induced Ca2+ elevation, Daudi cells were pretreated with ANF for 4 h,
      followed by treatment with BaP metabolites for 18 h. ANF completely reversed the
      rise in Ca2+ produced by BaP-7,8-diol, but had no effect on the Ca2+ elevation
      produced by BPDE. These results suggest that BPDE may be the ultimate P450
      metabolite responsible for Ca2+ elevation in human B cells. BaP-7,8-diol and BPDE
      were found to increase tyrosine phosphorylation in Daudi whole cell lysates and
      to increase tyrosine phosphorylation of two important Src-related protein
      tyrosine kinases (PTKs), Lyn and Syk. Inhibition of tyrosine phosphorylation by
      herbimycin A was found to largely prevent the increase in intracellular Ca2+
      produced by BaP-7,8-diol and BPDE, suggesting that Ca2+ elevation is coupled to
      increased tyrosine phosphorylation in Daudi. BPDE was found to produce a
      statistically significant increase in tyrosine phosphorylation of Lyn and Syk
      within 10 min of exposure. Collectively, these data demonstrate that certain P450
      derived metabolites of BaP may be responsible for PTK activation and an increase
      intracellular Ca2+, which may alter antigen receptor signaling in human B cells.

PMID- 9512731
TI  - Comparative in vitro and in vivo benzo[a]pyrene-DNA adduct formation and its
      relationship to CYP1A activity in two species of ictalurid catfish.
AB  - We have measured the formation and persistence of benzo[a]pyrene (BaP)-DNA
      adducts in the liver of two closely related species of fish, the brown bullhead
      (Ameriurus nebulosus) and the channel catfish (Ictalurus punctatus) using the 32P
      postlabeling method. Liver microsomal ethoxyresorufin-O-deethylase (EROD)
      activity, arylhydrocarbon hydroxylase (AHH) activity, and in vitro microsome
      mediated DNA binding were all significantly higher in the channel catfish. In an
      in vivo time-course experiment, fish were either induced with beta NF followed by
      a single BaP i.p. injection (20 mg/kg) or treated with corn oil. BaP-DNA adducts
      and EROD activity in liver were analyzed 1, 3, 7, 14, and 45 days after the BaP
      dosage. As in the in vitro experiments, EROD activities in channel catfish were
      significantly higher at most time points than in bullhead liver (p < 0.05).
      However, in contrast to the in vitro data, the BaP-DNA adduct profile revealed
      significantly higher levels of adducts in the bullhead than the channel catfish
      throughout the time course (p < 0.05). Prior induction with beta NF did not
      significantly affect the level or type of adduct binding to DNA in either
      species. Further characterization of the major adduct by HPLC confirmed it to be
      the anti-BPDE-dGuo adduct. Analysis of tissue distribution of [14C]BaP in the two
      species suggested similar absorption and initial distribution, but slower
      elimination from the liver of bullhead than the catfish. The BaP-adduct profiles
      were consistent with the relative species susceptibility to polycyclic aromatic
      hydrocarbon-induced liver neoplasia. EROD activities, however, were negatively
      associated with adduct levels following in vivo exposure.

PMID- 9512733
TI  - Age- and gender-related differences in the time course of behavioral and
      biochemical effects produced by oral chlorpyrifos in rats.
AB  - It is well known that young animals are generally more sensitive to lethal
      effects of cholinesterase-inhibiting pesticides, but there are sparse data
      comparing less-than-lethal effects. We compared the behavioral and biochemical
      toxicity of chlorpyrifos in young (postnatal Day 17; PND17) and adult (about 70
      days old) rats. First, we established that the magnitude of the age-related
      differences decreased as the rat matures. Next, we evaluated the time course of a
      single oral dose of chlorpyrifos in adult and PND17 male and female rats.
      Behavioral changes were assessed using a functional observational battery (with
      age-appropriate modifications for pre-weanling rats) and an evaluation of motor
      activity. Cholinesterase (ChE) activity was measured in brain and peripheral
      tissues and muscarinic receptor binding assays were conducted on selected
      tissues. Rats received either vehicle (corn oil) or chlorpyrifos (adult dose: 80
      mg/kg; PND17 dose: 15 mg/kg); these doses were equally effective in inhibiting
      ChE. The rats were tested, and tissues were then taken at 1, 2, 3.5, 6.5, 24, 72,
      168, or 336 h after dosing. In adult rats, peak behavioral changes and ChE
      inhibition occurred in males at 3.5 h after dosing, while in females the onset of
      functional changes was sooner, the time course was more protracted and recovery
      was slower. In PND17 rats, maximal behavioral effects and ChE inhibition occurred
      at 6.5 h after dosing, and there were no gender-related differences. Behavioral
      changes showed partial to full recovery at 24 to 72 h, whereas ChE inhibition
      recovered markedly slower. Blood and brain ChE activity in young rats had nearly
      recovered by 1 week after dosing, whereas brain ChE in adults had not recovered
      at 2 weeks. Muscarinic-receptor binding assays revealed apparent down-regulation
      in some brain areas, mostly at 24 and 72 h. PND17 rats generally showed more
      receptor down-regulation than adults, whereas only adult female rats showed
      receptor changes in striatal tissue that persisted for 2 weeks. Thus, compared to
      adults (1) PND17 rats show similar behavioral changes and ChE inhibition although
      at a five-fold lower dose; (2) the onset of maximal effects is somewhat delayed
      in the young rats; (3) ChE activity tended to recover more quickly in the young
      rats; (4) young rats appear to have more extensive muscarinic receptor down
      regulation, and (5) young rats show no gender-related differences.

PMID- 9512732
TI  - Lead exposure promotes translocation of protein kinase C activities in rat
      choroid plexus in vitro, but not in vivo.
AB  - Lead (Pb) exposure reportedly modulates PKC activity in brain endothelial
      preparations, which may underlie Pb-induced damage at the blood-brain barrier.
      Our previous work indicates that Pb accumulates in the choroid plexus and causes
      dysfunction of this blood-cerebrospinal fluid (CSF) barrier. The present studies
      were undertaken to test the hypothesis that Pb in the choroid plexus may alter
      PKC activity and thus affect the functions of the blood-CSF barrier. When
      choroidal epithelial cells in a primary culture were exposed to Pb (10 microM in
      culture medium), the membrane-bound PKC activity increased by 5.2-fold, while the
      cytosolic PKC activities decreased, an indication of the induction of PKC
      translocation by Pb. The effect of Pb on cellular PKC was concentration dependent
      in the range of 0.1-10 microM. We further evaluated PKC activity of the choroid
      plexus in rats chronically exposed to Pb in the drinking water (control, 50 or
      250 micrograms Pb/ml) for 30, 60, or 90 days. Two-way analysis of variance
      revealed a significant age-related decline of PKC activities in both cytosol and
      membrane of the choroid plexus. However, Pb treatment did not alter plexus PKC
      activities. In addition, we found that short-term, acute Pb exposure in rats did
      not significantly change PKC activities nor did it affect the expression of PKC
      isoenzymes in the choroid plexus. Our results suggest that Pb exposure may
      promote the translocation of PKC from cytosol to membrane in rat blood-CSF
      barrier in vitro, but not in vivo.

PMID- 9512734
TI  - Platelet-derived growth factor and pentoxifylline modulation of collagen
      synthesis in myofibroblasts.
AB  - Fibroblast proliferation and extracellular matrix accumulation are two major
      events occurring in fibrosis. Hepatic stellate cells are the major collagen
      producing cells of the liver and are transformed into proliferative
      myofibroblasts following activation. Whether proliferation and extracellular
      matrix production are regulated by the same cytokines is not known. Monocyte
      conditioned medium obtained from pigs with yellow phosphorus-induced hepatic
      fibrosis increased the collagen production by cultured procine myofibroblasts.
      Liver biopsies from these same fibrotic animals had increased levels of collagen
      alpha 1(I) and alpha 1(III) mRNA compared to control animals. Preincubation with
      platelet-derived growth factor (PDGF) B/B antibody significantly reduced the
      collagen-stimulating ability of the monocyte-conditioned medium. Recombinant PDGF
      stimulated proliferation in nonconfluent myofibroblasts and stimulated collagen
      production in confluent cultures of myofibroblasts without increasing cell
      number, suggesting that these events can occur independent of each other.
      Pentoxifylline and one of its active metabolites (metabolite-1) inhibited PDGF
      stimulated collagen production in cultured porcine myofibroblasts. These results
      demonstrate the importance of PDGF in the pathogenesis of liver fibrosis and
      provide evidence that pentoxifylline interferes with PDGF-mediated events during
      experimental liver fibrosis.

PMID- 9512735
TI  - Dynamics and impact of tick-borne diseases of cattle.

PMID- 9512736
TI  - Cattle theileriosis in China.
AB  - Amongst the piroplasmoses of livestock in China, the commonest theilerioses are
      caused by Theileria annulata, T. sergenti and T. mutans. Research carried out
      over many years has shown these to be distributed mainly in Northern China but
      they also occur in Southern China. T. annulata and T. sergenti are the most
      troublesome, affecting large numbers of cattle, especially those of exotic
      breeds. The incident rate and numbers of fatalities vary widely between areas and
      breeds of cattle. T. annulata is the most virulent species having an incident
      rate of 11-46% for indigeneous cattle and causing death rates of between 11
      40.8%. For exotic cattle in areas free of T. annulata the sickness rate is up to
      61% and mortality rates up to 31%. T. sergenti is avirulent in cattle and
      clinical symptoms are rarely observed, however, in some areas the infection rate
      could possibly be as high as 97.5%. Dairy and hybrid cattle imported from other
      places proved highly susceptible, with mortality rates possibly reaching 14%. The
      pathogenic forms, clinical signs, tick vectors and the effects of chemical and
      immune intervention are also discussed in this paper.

PMID- 9512737
TI  - Theileriosis of sheep and goats in China.
AB  - Theileriosis is an important disease of sheep and goats in West China. Its main
      distribution includes Qinghai, Gansu, Ningxia, Inner Mongolia, Shaanxi and
      Sichuan. The epidemic period is from late March to July with April-May being the
      peak months. This is the period of most intensive tick attack by Haemaphysalis
      qinghaiensis (77.2-99.24%) during the year. It has been proved that the nymphs
      and adults, which develop from larvae and nymphs engorged on infected sheep or
      goats can transmit the pathogen. Experimental infections revealed the incubation
      period, clinical signs and the pathogen's morphological characteristics. The
      disease was more serious in lambs and exotic adult animals than native adult
      animals. The sickness rates of lambs, exotic and native adult animals were 78
      85%, 41% and 9% respectively; death rates were 81.41%, 62.5% and 65%
      respectively. Clinical prophylaxis, chemical therapy and destruction of ticks
      have been carried out with antiparasitic compounds to control the disease since
      1982. Experiments demonstrated that the curative rate was up to 76-86%, but no
      satisfactory prophylactic methods were found.

PMID- 9512738
TI  - Babesiosis in China.
AB  - The importance of babesiosis in livestock in China is discussed and mainly
      focused on bovine and equine babesiosis. Babesiosis is still one of the most
      important diseases affecting livestock and has caused great economic loss. Nine
      species of Babesia have been recognized in livestock: B. bigemina, B. bovis, B.
      major, B. motasi, B. ovis, B. perroncitoi, B. trautmanni, B. equi (Theileria
      equi), B. caballi. The distribution of Babesia follows the distribution of the
      tick vectors. The main vectors of bovine babesiosis are the one-host tick
      Boophilus microplus and the three-host ticks Rhipicephalus haemaphysaloides
      haemaphysaloides, Haemaphysalis punctata and Haemaphysalis longicornis. Bovine
      babesiosis has caused significant losses in milk and meat from cattle in most
      parts of China. The disease is also a barrier to improving productivity of local
      cattle by cross-breeding due to the high mortality of genetically superior but
      highly susceptible cattle, especially dairy cattle, imported from Babesia-free
      areas. Dermacentor nuttalli is the major vector of equine babesiosis and the tick
      is distributed in almost all parts of North China. Outbreaks of equine babesiosis
      have not been very common, but in some districts the disease has seriously
      affected horses, donkeys and mules.

PMID- 9512740
TI  - Ticks and tick-borne bovine piroplasmosis in the Southmountain pasture of Hunan
      Province, China.
AB  - Ticks and tick-borne bovine piroplasmosis is one of the most serious diseases
      affecting cattle bred in the Southmountain pasture of Hunan province. An
      investigation carried out from 1992 to 1995 showed that Theileria sergenti was
      found in the blood of disease-stricken cows. Ticks were collected from cattle.
      The species concerned (three genera and four species of ticks: Haemaphysalis
      vietnamensis, Haemaphysalis longicornis, Ixodes sinensis and Boophilus microplus)
      were identified by microscopy and their numbers recorded every month. Because H.
      longicornis is a three-host tick, with the larvae, nymphs and adults all
      infesting cows and seasonal fluctuations in nymphs and adults correlating with
      theileriosis outbreaks, this tick species was a potential vector of T. sergenti.
      Epidemiological studies indicated that this disease usually occurred in summer or
      autumn. The disease attacked calves from May to August reaching a peak in June or
      July (as happened from 1992-1994). In cattle, the disease occurred from June to
      September with a peak in September. The following pathological lesions were
      observed: haemorrhages were seen in the subcutaneous tissues and serosa, in the
      intestinal mucosa and the mesenteric lymph nodes. The surface of the abomasum
      looked like a piece of red cloth. The liver was enlarged, its edge blunt and
      curled over. The gall bladder was filled with tawny coloured bile. The spleen was
      enlarged and dark brown. The heart was enlarged with numerous haemorrhagic foci
      in the auricle. The blood clotted incompletely. Sick cattle were treated with
      Berenil and imidocarb and the death rate was reduced from 26% to 5.9%.

PMID- 9512739
TI  - Babesiasis in Nanjing area, China.
AB  - This article discusses the tick-borne babesiases which harm dairy cattle,
      buffaloes and dogs. In addition, the pathogen, vector, seasonal occurrence,
      hosts, symptoms, pathological changes and treatment are summarized and analysed.
      The pathogens in this area were identified as Babesia bigemina, B. bovis and B.
      gibsoni; the vectors as Boophilus microplus, Rhipicephalus haemaphysaloides,
      Haemaphysalis longicornis. Affected buffaloes were found from April to September,
      peak numbers occurred between May and July. Affected dairy cattle were most
      numerous in July and August. Hunting dogs were the most affected dogs. Infected
      dogs were found from February until the beginning of December; peak numbers
      occurred from September to November. Affected animals were acute cases. Symptoms
      and pathological changes were obvious, but jaundice was rare in dogs. Acaprin,
      acriflavine, imidocarb and berenil were used early and late. Their effect was
      ideal but resistance has developed to these drugs.

PMID- 9512741
TI  - Attempted transmission of Babesia major by Boophilus microplus.
AB  - Two experiments was carried out to determine if Babesia major could be
      transmitted by Boophilus microplus. In experiment 1, a Babesia-free batch of
      laboratory reared Bo. microplus larvae were applied to an intact calf infected by
      inoculation with a B. major stabilate. The calf showed a B. major parasitaemia
      while the larvae, nymphs and adult ticks were engorging. The engorged females
      were cultured and batches were incubated at one of the three following
      temperatures: 24, 28 or 32 degrees C. Approximately 10,000 larvae derived from
      each of the females were used to infest each of three splenectomized calves. In
      experiment 2, Babesia-free Bo. microplus larvae were applied to a splenectomized
      calf; the calf was injected with B. major stabilate and showed a B. major
      parasitaemia during the adult stage of tick development. The engorged females
      were incubated at room temperature and the resulting larvae (approximately
      10,000) were used to infest a splenectomized calf. Examination of blood films for
      the presence of B. major from the four calves infested by the second generation
      larvae in the two experiments were negative.

PMID- 9512742
TI  - Studies on buffalo babesiosis in Hubei Province, China.
AB  - The present paper summarises our recent studies on buffalo babesiosis in the
      Hubei province of China. It describes the pathogen and the epidemiology of the
      disease, the tick vector and its biology, control, immunological diagnosis,
      methods of in vitro cultivation of the pathogen and their practical applications.
      The identify of the pathogen is discussed in detail.

PMID- 9512743
TI  - Studies on the in vitro cultivation of Babesia from buffaloes.
AB  - This paper summarizes a recent study on the in vitro cultivation of Babesia from
      buffaloes. Buffalo Babesia parasites were cultured many times by the
      microaerophilous stationary phase (MASP) method of Levy and Ristic (1980) with
      some modifications. The culture-derived Babesia organisms were similar to forms
      seen in the blood of infected buffaloes and the pathogenicity of these organisms
      was unchanged. Factors influencing the in vitro cultivation are discussed in
      detail.

PMID- 9512744
TI  - Studies on the pathogenicity of Babesia bovis in water buffaloes after
      cryopreservation and resuscitation.
AB  - Packed erythrocytes infected with Babesia bovis were mixed with an equal volume
      of 16% dimethyl sulphoxide (DMSO) in Alsever's solution and dispensed into 1.5 or
      5 ml cryotubes. The vials were kept in liquid nitrogen (-196 degrees C) for 26,
      78, 142 or 149 days. The samples were removed from the liquid nitrogen container
      and rapidly thawed in a 40 degrees C water bath. The thawed blood successfully
      infected splenectomised buffalo calves by injection via subcutaneous or
      intravenous or via intravenous and subcutaneous routes. The parasites, typical B.
      bovis, were discovered in red blood cells 5, 8 or 9 days after inoculation. The
      highest percentage of parasitised erythrocytes (PPE) was 15%. The babesiosis
      resulting from cryopreserved parasites was the same as that resulting from fresh
      parasites inoculated by ticks. Typical clinical signs were found, such as
      continuous fever (the highest temperature was 41.3 degrees C), anaemia, icterus
      and haemoglobinuria. Infected calves, which were not treated, died.
      Cryopreservation is a simple and reliable method for longterm preservation of B.
      bovis of water buffaloes.

PMID- 9512745
TI  - An unidentified species of Theileria infective for cattle discovered in China.
AB  - Infection experiments, morphological observations and transmission experiments
      were conducted with an unidentified Theileria sp. isolated from a naturally
      infected ox. The results showed that the protozoa could multiply extensively in a
      splenectomized ox and the parasitaemia could reach 52.69%. The Theileria sp. was
      polymorphic: being pear-shaped, circular, elliptical, rod-like, comma-shaped,
      three-leafed- or cross-shaped and having many other irregular-shapes which were
      seldom detected. In erythrocytes, the anaplasma-like protozoa grew, producing
      protoplasm which could extend and clump together, and developed into many
      polymorphic protozoa. Some of the protozoa propagated themselves by budding. The
      protozoa could not be transmitted by Haemaphysalis longicornis or Hyalomma
      detritum. The pathogenicity, vector ticks and life cycle of this protozoan are
      unknown.

PMID- 9512746
TI  - Detection of Babesia bovis using a DIG-labeled DNA probe.
AB  - A plasmid DNA containing the inserted Babesia bovis cDNA clone designated c51A
      was used to prepare a DNA probe for B. bovis. The purified 0.6 kb specific DNA
      fragment was labeled by DIG DNA labeling. After denaturation, the probe was
      hybridised with the blotted target DNA extracted from bovine red blood cells
      infected with B. bovis or other protozoa or bovine red blood cells plus extra
      white blood cells. It was found that the probe produced from purified 0.6 kb DNA
      fragment could detect sample of B. bovis DNA equivalent to 0.015 microliter of
      10% whole infected blood. Compared to the same DNA fragment labeled with
      photobiotin, this new probe is more sensitive giving a darker hybridization
      signal, a lighter hybridization background and without any non-specific
      reactions. These results indicated that this DIG-labeled B. bovis C5lA probe
      could provide a sensitive and specific method to diagnose clinically suspected B.
      bovis infections and distinguish B. bovis DNA from other haemoprotozoan
      infections.

PMID- 9512748
TI  - Studies on the comprehensive control of babesiasis in cattle and buffaloes.
AB  - To obtain a highly effective method for controlling babesiosis in cattle and
      buffalo, an epidemiological survey was carried out at Zuiyun village in Hubai
      Province. On the grounds of the epidemiological data, control measures which
      included preventive drugs and killing the vectors were devised. After two years
      of control no clinical cases of bovine babesiosis were found. The average number
      of ticks on cattle or buffalo decreased from 9-282 to 0-11.3. Good results were
      obtained in another epidemic area using this control method. These results
      indicated that this technique of controlling babesiosis is highly effective.

PMID- 9512749
TI  - Observations on the treatment of natural haemosporidia infections by total
      alkaloid of Peganum harmala L. in cattle.
AB  - Eighty two cattle naturally infected with haemosporidians were treated with total
      alkaloid hydrochloride of Peganum harmale L. (0.5 mg/kg/day). Fifty eight cases
      with Theileria sergenti showed a cure rate of 86%; thirteen cases with Theileria
      annulata showed a cure rate of 85%; eight cattle infected with Babesia bigemina
      showed a cure rate of 88% and three cases of Anaplasma marginale were completely
      cured. The results suggested that the curative effect of total alkaloid of P.
      harmale was better than that of diminazene aceturate and produced minimal side
      effects. The alkaloid could also be administered to pregnant animals. It was
      concluded that the total alkaloid of P. harmale showed a marked effect as a
      treatment for haemosporidican infections in cattle.

PMID- 9512747
TI  - The cure of acute Babesiasis perroncitoi in swine.
AB  - From June to August in 1988, a total of 64 pure-bred Landrace, Yorkshire (large
      white) and Inner Mongolian Black Swine from a farm in Huhehot were affected with
      a disease, 13 died. The pathogen was confirmed primarily to be Babesia
      perroncitoi. The drugs used for treatment were Berenil and Acaprin. The
      intramuscular dose for Berenil was 3 mg per kilogram weight. The subcutaneous
      dose for Acaprin was 0.8 mg per kilogram weight. All of which had satisfactory
      results. In the same season in the second year and the third year, the disease
      was also reported, but all sick animals were cured.

PMID- 9512750
TI  - Effect of total alkaloid of Peganum harmala L. in the treatment of experimental
      haemosporidian infections in cattle.
AB  - Cattle experimentally infected with Babesia bigemina or Theileria sergenti or
      mixed infestations of the two parasites were treated with Total Alkaloid of
      Peganum harmala L. The results showed that treatment was effective against B.
      bigemina infection, had a marked effect on the course of infection with T.
      sergenti and some effect on the course of the mixed infection.

PMID- 9512751
TI  - Vaccines against hemoparasitic diseases in Israel with special reference to
      quality assurance.
AB  - Four vaccines against hemoparasitic diseases (anaplasmosis, babesiosis and
      theileriosis) and a vaccine against besnoitiosis are currently used in Israel.
      These vaccines contain live attenuated parasites derived from cell culture
      (Theileria annulata and Besnoitia besnoiti) or from blood of infected,
      splenectomized calves (Babesia bigemina, B. bovis and Anaplasma centrale).
      Cryopreserved master seed is used to initiate production of the vaccines. Quality
      control performed during the preproduction period is particularly important with
      blood-derived vaccines. Post production quality control comprises sterility,
      potency (viability of immunizing organisms), safety (degree of attenuation) and
      efficacy (capacity to protect against virulent parasite stock). All vaccines are
      stored and dispatched to the field in a concentrated frozen state. The culture
      derived vaccines are safe for all varieties of cattle, regardless of age or
      physiological condition, whereas the blood-derived vaccines are recommended
      mainly for young cattle, the age limit varying with the type of vaccine and breed
      of cattle. The viability of T. annulata infected cells in the anti-theilerial
      vaccine is tested after thawing by in vitro plating efficiency and the
      infectivity of blood-derived vaccines is tested by titration in susceptible
      cattle.

PMID- 9512752
TI  - Vaccines, genetics and chemicals in tick control: the Australian experience.

PMID- 9512753
TI  - Research on the schizont cell culture vaccine against Theileria annulata
      infection in Xinjiang, China.
AB  - Theileria annulata infection (TAI) is one of the most serious diseases of cattle
      in Xinjiang Autonomous Region of Uigur Minority Nationality. It has been recorded
      in 14 prefectures, except the Tulufan Prefecture, but the enzootic areas are
      mainly distributed around the Zhunger Basin and Talim Basin. According to the
      records collected in the ten years before vaccination with the schizont cell
      culture vaccine was carried out, the average incidence rate of TAI in enzootic
      areas was 7.22% and the mortality rate was 24%. The milk production of cattle
      suffering from TAI was sharply decreased, and there were usually abortions in
      pregnant cows. The incidence rate and mortality rate were greater in high grade
      cattle, so TAI was a constraint to improving cattle breeds. To control this
      disease effectively in Xinjiang, researchers at the Xinjiang Academy of Animal
      Science began to study the schizont cell culture vaccine in 1972. In 1977 an
      immortalised cell line was achieved from a primary cell culture starting with
      white blood cells from cattle suffering from acute TAI caused by an artificial
      tick bite. The cell culture medium mainly consisted of calf serum, lactalbumin
      hydrolysate, Eagles' medium DMEM and three antibiotics. As a vaccine, the above
      cells were mixed with preserving medium containing gelatin. This paper describes
      the experiments on the immunological properties of the vaccine carried out in
      subsequent years. Up to 1996, vaccine doses for 1,186,150 cattle have been
      produced and sold. This vaccine has had a critical effect on the control of TAI
      in Xinjiang. Owing to the sharp decrease in the incidence rate and mortality rate
      of TAI after cattle were vaccinated, the annual economic benefit of the vaccine
      is at least 1,620,000 yuan.

PMID- 9512754
TI  - Lowered vaccine dose for immunisation of calves against tropical theileriosis
      using Theileria annulata lymphoblasts.
AB  - Bovine tropical theileriosis is of high incidence in calves below 2 months old in
      India. The Theileria cell culture vaccine evolved by the Punjab Agricultural
      University (PAU) was evaluated previously for its efficiency and safety in
      younger calves, both experimentally and in the field. The dose of cells used for
      vaccination was regulated at 1.75 to 2 x 10(6) cells. This study, which was
      undertaken to assess the minimum number of cells which would be effective and
      safer for vaccination, showed that optimal protection was given by a dose of 1 x
      10(6) cells.

PMID- 9512755
TI  - Responses in animals vaccinated with the Theileria annulata (Hisar) cell culture
      vaccine.
AB  - Bovine tropical theileriosis caused by Theileria annulata is an economically
      important disease of cattle in India. The disease has assumed paramount
      importance with the intensification of cross-breeding programmes aimed at
      enhancing milk production in the country. To control this disease, a cell culture
      vaccine was developed in this department by continuous passaging of T. annulata
      (Hisar) schizonts in vitro. Current work in this department has concentrated on
      the epidemiology of theileriosis: development of the cell culture vaccine for
      very young calves and pregnant cows; evaluation of serological responses using
      immunofluorescent antibody (IFA) tests and Enzyme-linked immunosorbent antibody
      assays (ELISA); studies on the duration of immunity stimulated by the cell
      culture vaccine; the immune/susceptible status of calves born to vaccinated dams.
      Results have shown the following. Clinical cases of theileriosis were mainly
      observed in young calves below two months of age followed by adults in exotic and
      cross-bred animals. Amongst indigenous animals, only young calves below two
      months of age suffered from clinical disease. Clinical cases of theileriosis
      mainly occurred between the months of April to October. The T. annulata schizont
      cell culture vaccine developed in the department was extensively used in the
      susceptible calves and pregnant/lactating cows in the field. Sufficiently high
      antibody titres were detected by both schizont as well as piroplasm antigen using
      both ELISA and IFAT. The results indicated that the vaccine was safe, potent and
      effective for all breeds and age groups of cattle under field conditions. ELISA
      was standardised for T. annulata using three antigens, viz.: soluble piroplasm,
      soluble schizont and cellular schizont antigens. Comparison of results with IFAT
      showed that ELISA is more sensitive, objective, reliable and specific as well as
      less cumbersome than IFAT. Piroplasm, cellular schizont and soluble schizont
      antigens were found to be suitable for the detection of antitheilerial antibodies
      as per their order in ELISA. Studies on the duration of immunity stimulated by
      the T. annulata schizont cell culture vaccine indicated that immunity started
      waning after six months. Calves born of dams immunised against T. annulata with
      the cell culture vaccine were found to be fully susceptible to theileriosis soon
      after birth. This indicated that there was no passive transfer of immunity from
      dams to their offspring through colostrum.

PMID- 9512756
TI  - Revaccination with the same Theileria annulata infected cell line may not be
      feasible for boosting immunity against tropical theileriosis.
AB  - A model for studying re-immunisation using skin grafting was developed as the
      allogeneic responses produced by T. annulata cell lines were similar to those
      produced by skin grafting. Appearance of schizonts and piroplasms post
      immunisation was either delayed or prevented by already existing allogeneic
      responses. Isolation of parasite infected cell lines from lymph node biopsies and
      peripheral blood after cell line immunisation was also delayed or prevented by
      already existing allogeneic responses. Ability to isolate cell lines after
      immunisation correlated with protection i.e. if no parasite infected cell line of
      donor origin was isolated after immunisation, there was no protection. Allogeneic
      responses delayed or prevented the appearance of MHC I restricted parasite
      specific cytotoxic T lymphocytes post-immunisation. If the parasite transfer was
      prevented after immunisation; animals were fully susceptible to challenge. These
      experiments showed that allogeneic responses, generated in animals after
      immunisation with T. annulata schizont cell culture vaccine, can block parasite
      transfer and further development or enhancement of immunity against the parasite
      at the time of second immunisation with the same cell line. The observations are
      of immediate importance in endemic areas where T. annulata infected cell culture
      vaccines are being used. They are even more relevant in countries where animals
      are regularly moved between theileriosis free and endemic areas. It may not be
      advisable to re-immunise animals with the same cell line as that used for first
      vaccination.

PMID- 9512757
TI  - Control of Theileria sergenti infection by vaccination.
AB  - Bovine piroplasmosis caused by Theileria sergenti is a major cause of economic
      loss in grazing cattle in Japan. Infected calves show chronic anaemia with
      intraerythrocytic piroplasms and occasionally die in severe cases. We found that
      parasite stocks and isolates consist of genetically and antigenically mixed
      populations. To differentiate parasite populations bearing 3 allelic forms of
      p32/34, an immunodominant piroplasm surface protein, 3 sets of oligonucleotide
      primers were designed to amplify either of 3 alleles by polymerase chain reaction
      (PCR). By using this allele-specific PCR, we found that the majority of T.
      sergenti-infected calves in Japan harbored mixed parasite populations bearing C
      and I type parasites. To control Theileria infection, we produced 2 vaccine
      candidates: recombinant baculovirus p32 and synthetic peptide containing Lys-Glu
      Lys (KEK) motif. Immunization with either recombinant p32 or synthetic peptide
      containing KEK sequences with Freund's complete adjuvant resulted in low
      parasitemia and reduced the clinical symptoms compared to control calves.
      Interestingly, the parasite with the p32 allelic form corresponding to the one
      used as the immunogen was suppressed.

PMID- 9512758
TI  - An immunisation trial with in vitro produced Babesia bigemina exoantigens.
AB  - Bovine babesiosis, caused by Babesia bigemina, is an important tick-transmitted
      haemoprotozoan disease in the tropics. This study evaluated the immunoprotective
      efficacy of in vitro produced B. bigemina exoantigens in bovine calves. The
      calves inoculated with B. bigemina exoantigens did not show any clinical,
      parasitological or hypersensitivity reactions after inoculation. They withstood
      challenge without showing any clinical symptoms except a transient thermal
      reaction. In contrast, two out of four control calves exhibited clinical symptoms
      of babesiosis and one died. On challenge, there was a significant reduction in
      the haematological values of both groups. However, this was more pronounced in
      the control animals. Challenge resulted into a normocytic hypochromic anaemia.
      The vaccinated animals revealed a significant rise in antibody titres after
      vaccination as well as after challenge as detected by a single dilution ELISA.
      The rise in antibody titres of control animals was only moderate. Inoculation of
      B. bigemina exoantigens induced a protective immune response in the vaccinated
      animals which could protect them from infected blood challenge.

PMID- 9512759
TI  - Macroschizonts of Theileria annulata as vaccine and diagnostic tools.
AB  - T. annulata-infected cells present infection-associated peptides. These peptides
      represent target molecules of the cytotoxic acting cells. Their preparation and
      characterization may help to develop a sub-unit vaccine. Our studies show that
      macroschizont-infected bovine cells can be used as parasite antigen in serology
      for the detection of parasite-specific antibodies in serum of infected animals.
      Primers derived from the macroschizont of T. annulata can be used as molecular
      tools for the detection of parasite DNA in blood samples of carrier cattle.

PMID- 9512760
TI  - Parasite-mediated steps in immune response failure during primary Theileria
      annulata infection.
AB  - "Exotic" European cattle are highly susceptible to T. annulata infection. In
      immunised animals, several effective anti-parasite responses can be demonstrated,
      such as anti-macroschizont cytotoxic T cells (CTL), and nitric oxide killing of
      parasites. The failure of infected animals to mount an effective primary immune
      response suggests that the presence of the parasite directly interferes with the
      development of immunity. When the activation pathways of CD4+ T cells in draining
      lymph nodes were examined during the course of a primary infection it was found
      that the development of this essential arm of the immune response was altered.
      Instead of interacting with antigen presenting cells in the paracortex, the
      majority of CD4+ T cells were rapidly activated by developing infected cells in
      the medulla of the node. Activation of T cells by infected cells also drastically
      alters the cytokines produced by the T cells. During effective immune responses,
      the principal cytokine involved appears to be IL-2, with only small, controlled
      "bursts" of IFN gamma production. However, IL-2 responsiveness is only transient
      in animals undergoing primary infection, while IFNg production is greatly
      elevated. IFN gamma does not appear to control parasitised cells, and may even
      aid the growth of infected macrophages--large numbers of macrophages enter the
      cell cycle during the peak period of IFN gamma production. Uncontrolled parasite
      induced IFN gamma production is also likely to account for the local failure of
      antibody responses. Germinal centres in infected lymph nodes lose normal
      morphology, with IFN gamma sensitive zones failing to develop. A third strategy
      which the parasite uses to evade immune response destruction is through affecting
      CTL activity. CTL in infected draining lymph nodes lose expression of the
      adhesion molecule CD2--a molecule is essential in adherence to target cells for
      lysis. CD2- CTL are unable to lyse macroschizont infected cells.

PMID- 9512761
TI  - Protective immune responses to Theileria annulata of relevance to vaccine
      development.
AB  - A series of projects on Theileria annulata funded by the European Union
      (STD1/STD2/STD3) have provided convincing evidence that macrophage and natural
      killer (NK) cell-dependent immune mechanisms may directly control the
      proliferation of different stages of T. annulata in cattle. The evidence for this
      conclusion and the implications for vaccine development are discussed in the
      following paper.

PMID- 9512762
TI  - Neurological syndromes of organophosphorus compounds.
AB  - In addition to the acute cholinergic poisoning, organophosphorus (OP) compounds
      are capable of producing several subacute, delayed and chronic neurological,
      neurobehavioural and psychiatric syndromes. These include the intermediate
      syndrome, the organophosphate induced delayed neuropathy (OPIDN) and a number of
      chronic neurological and psychiatric manifestations lumped in this review under
      the term chronic organophosphate induced neuropsychiatric disorder (COPIND). A
      critical review of the concept of the neuropathy target esterase (NTE) inhibition
      and ageing as a marker of OPIDN and the related hen test is presented. It is
      concluded that the use of the hen test as an exclusive screening test for
      neurotoxicity of organophosphorus compounds is flawed. A number of recent studies
      are presented to demonstrate the unreliability of the test and flaws of
      scientific concepts underlying the hen test which is used to identify OPs as safe
      and "non-neurotoxic". The components of this new COPIND syndrome are described
      and the evidence for its existence is reviewed. Studies are in progress to
      further determine the profile of this syndrome and to define the overlap between
      its various components. The review also attempts to determine the clinical
      features so far described of these components and the investigations or markers
      used to identify and characterize COPIND and the behaviour of these markers.
      Evidence for chronic neurological/psychiatric effects of OP compounds have come
      from case studies, clusters of neurological diseases or from epidemiological
      investigations. New concepts in neurotoxicology are being produced from recent
      studies which may necessitate a new radical approach to the assessment of
      neurotoxicity of pesticides before releasing them for widespread use.

PMID- 9512763
TI  - Adverse effects of cytotoxics-platinum agents.

PMID- 9512764
TI  - ICH4: a report and background.

PMID- 9512765
TI  - Infrared absorbances of protein side chains.
AB  - The spectral parameters of amino acid residue side chain and peptide bond
      absorptions in the region 1800-1440 cm-1 have been obtained by using an inverse
      matrix method applied to the infrared spectra of 42 amino acids, dipeptides, and
      higher peptides in aqueous solution. In addition the pH-dependent extinction
      coefficients of the amino acid and peptide COO-/NH3+ end groups were derived. It
      is shown that the secondary structure prediction accuracy of proteins by
      multivariate data analysis methods increases slightly, if the side chain
      absorbances of the residues asparagine, glutamine, aspartic acid, glutamic acid,
      arginine, tyrosine, and lysine are subtracted from the amide I and amide II
      region.

PMID- 9512766
TI  - Enzyme-based microassay for accurate determination of soman in blood samples.
AB  - Successful medical therapy for nerve agent intoxication requires early diagnosis
      and treatment. Current clinical diagnostic methods do not permit early or
      definitive confirmation of intoxication. To improve the chances of successful
      medical therapy against nerve agent intoxication, a sensitive enzyme-based
      microassay for rapid and accurate quantification of residual soman levels in
      blood was developed. The new analytical technique is based on the linear
      correlation between residual eel acetylcholinesterase activities and the
      inhibitor concentration. Blood samples were deproteinized with perchloric acid,
      followed by immediate neutralization after deproteinization. The mixtures were
      centrifuged at 3000g and the supernatant was directly assayed for soman. The
      sensitivity of the technique (18-1820 pg/ml blood) is comparable to that attained
      by GC-FID analysis (250 pg/ml blood). To facilitate routine analysis, the linear
      range of the assay was optimized to span over a factor of 100 (0.1-10 nM), with a
      typical correlation factor of at least 0.999 (six standards). The assay accuracy,
      checked with four different concentrations of soman, was within +/- 10%. The
      assay capability in monitoring the pharmacokinetic of soman was validated using
      both in vitro and in vivo rat models.

PMID- 9512767
TI  - Analysis of hydroxyproline and hydroxyproline-arabinosides of plant origin by
      high-performance anion-exchange chromatography-pulsed amperometric detection.
AB  - The plant cell wall hydroxyproline-rich glycoprotein (HRGP), also called
      extensin, contains arabinose and oligoarabinoside side chains O-glycosidically
      linked to hydroxyproline (Hyp). We present a highly sensitive method for
      determining both the glycosylation pattern and the Hyp content of HRGP requiring
      only nanomole amounts of each Hyp-compound for accurate determination. This
      method is based on anion-exchange chromatography followed by pulsed amperometric
      detection of the Hyp-oligoarabinosides and Hyp released from HRGP by 0.22 M
      Ba(OH)2 hydrolysis, which cleaves only peptidyl bonds. A sodium acetate gradient
      (0-250 mM) in 150 mM NaOH elutes Hyp and the Hyp-oligoarabinosides Hyp-(Ara)1-5
      in less than 40 min. We have used this procedure to determine the glycosylation
      pattern of Hyp in plant cell walls, without prior isolation of HRGP.

PMID- 9512768
TI  - In situ measurements of ribulose-1,5-bisphosphate carboxylase activity by nuclear
      magnetic resonance.
AB  - High-resolution NMR spectroscopy is demonstrated to be capable of monitoring in
      situ the carboxylation reaction catalyzed by ribulose-1,5-bisphosphate
      carboxylase. Specific activities are determined for three enzymes from different
      sources containing higher plant and photosynthetic bacteria, and they are in
      agreement with those measured by other methods. Several important features of the
      reaction have been confirmed at the atomic level. A decrease in activity with
      time after the reaction started has also been observed for both enzymes with L8S8
      and L2 structures from photosynthetic bacteria and higher plants, suggesting that
      the "fallover" of activity may be a more general phenomenon. 1H spectra obtained
      with H2O as solvent provide the most efficient quantitative measurement of the
      reaction product, 3-phosphoglycerate. 31P spectra give essentially the same
      result as 1H NMR but have the advantage of showing the degree of reaction at any
      time during the reaction. The incorporated carbon atom is unequivocally
      identified as the C-1 carbon of 3-phosphoglycerate from the 13C spectrum.

PMID- 9512769
TI  - Lectin coprecipitative isolation from crudes by Little Rock Orange ligand.
AB  - Matrix ligands are intended for upstream use with dilute crudes on a large scale,
      splitting out sought-for proteins by coprecipitating them as dense, protected
      aggregates. Matrix ligand coprecipitation is rapidly, quantitatively reversible,
      by pH shifting and trapping matrix ligands on ion exchange resin, releasing the
      sought-for protein. Four lectins, wheat germ agglutinin, peanut lectin,
      concanavalin A, and Phaseolus vulgaris (red kidney bean) lectins, were
      coprecipitated from crude extracts, 0.05 to 0.4% crude protein, in a single step
      using Little Rock Orange matrix ligand. All were compared in specific activities
      (erythrocyte agglutination) and in SDS-PAGE analysis with the four corresponding
      commercial lectins purified by affinity chromatography. All four matrix
      coprecipitated ligands were specifically active within range of the corresponding
      vendor (Sigma Co.) affinity chromatography-purified lectins. The matrix ligand
      coprecipitative technique requires optimization of ligand-protein (crude) ratios,
      denoted y, and determination of suitable pH ranges for coprecipitation relative
      to lectin isoelectric pH. These parameters control electrostatic ion pair
      association: ligand head anion binding to cationic target proteins. The
      coprecipitative and protective powers of new ligands like Little Rock Orange,
      their ability to scavenge sought-for lectins from dilute crudes, depend on ligand
      organic tail-tail association. After the strong anion heads of ligands bind to
      cationic proteins, their organic tails stack and draw the ligand-protein
      complexes together as aggregated coprecipitates.

PMID- 9512770
TI  - Interaction of iron with polyphenolic compounds: application to antioxidant
      characterization.
AB  - Antioxidant action of flavonoids and polyphenolics was analyzed in relation to
      iron coordination. Flavonoids including baicalein, baicalin, quercetin, and rutin
      showed little or no reducing activity, and enhanced the autooxidation of Fe2+
      ion. Ascorbate-mediated reduction of iron was rather inhibited by flavonoids.
      Nonflavonoid polyphenolics such as protocatechuic acid and chlorogenic acid, on
      the contrary, showed a potent iron-reducing ability, and protected Fe2+ ion from
      autooxidation completely. Both flavonoids and nonflavonoids effectively inhibited
      the formation of thiobarbituric acid-reactive substances as a marker of lipid
      peroxidation of microsomes from rat liver. Flavonoids act as an antioxidant by
      inhibiting the oxygen radical formation through the enhanced oxidation of Fe2+
      ion as the prooxidant. Antioxidant properties of nonflavonoids can be explained
      by the formation of inactive Fe(2+)-polyphenol complex, which cannot react with
      oxygen, and/or can scavenge reactive oxygen species. Analysis of the action of
      polyphenolics on the iron redox state may be useful for characterization of the
      antioxidant effect.

PMID- 9512771
TI  - Assessment of nitric oxide production by measurement of [15N]citrulline
      enrichment in human plasma using high-performance liquid chromatography-mass
      spectrometry.
AB  - Nitric oxide (NO) is formed by a class of NO synthases (NOS), which convert
      arginine into citrulline. A decreased in vivo NO availability can be the result
      of an increased NO inactivation or a decreased NO production. The latter can be
      assessed by measurement of isotopic enrichment of plasma citrulline during
      infusion of isotopically labeled arginine. The potential of high-performance
      liquid chromatography (HPLC) coupled to mass spectrometry (MS) to determine
      enrichments of [15N2]arginine and [15N]-citrulline in plasma during infusion of
      [15N2]arginine in humans was investigated. Two types of MS instruments were
      evaluated: a sector-type mass spectrometer equipped with a frit fast-atom
      bombardment (FAB) interface and a quadrupole instrument with electrospray
      ionization (ESI). FAB-MS appeared to be unsuitable for determination of isotope
      ratios, because background ions influenced the observed isotope ratio in an
      unpredictable way. In combination with either off- or on-line reversed-phase
      HPLC, ESI-MS proved to be a more reliable technique. However, the amount of
      material that is introduced in the mass spectrometer is critical and should be
      carefully controlled. During infusion of [15N2]arginine in 14 healthy subjects, a
      mean arginine-to-citrulline conversion rate of 0.22 +/- 0.07 (SD) mumol.kg-1.h-1
      was found. In 4 subjects who received an intravenous infusion with the NOS
      antagonist L-NMMA, the conversion rate decreased from 0.30 +/- 0.14 to 0.10 +/-
      0.06 mumol.kg-1.h-1. It is concluded that ESI-MS in combination with HPLC can be
      successfully applied for determination of arginine and citrulline enrichments in
      plasma, thus providing a useful tool for assessment of in vivo NO production.

PMID- 9512772
TI  - Chemiluminescent imaging of enzyme-labeled probes using an optical microscope
      videocamera luminograph.
AB  - A chemiluminescent system has been developed for ultrasensitive, quantitative
      analysis as well as visualization of the spatial distribution of biomolecules
      such as antigens, enzymes, antibodies, DNA probes in tissue, or cells. The system
      consists of a low-light imaging Vidicon videocamera connected to an optical
      microscope, able to measure light at the single photon level and perform 3D image
      analysis of the subcellular distribution of the analyte. The concentration and
      the spatial distribution of enzymes, or enzyme-labeled biospecific reagents can
      be determined using appropriate chemiluminescent substrates. Analytes are also
      determined with coupled enzymatic reactions terminating in light emission.
      Oxirane acrylic beads (250-micron-diameter macroporous particles) with
      immobilized horseradish peroxidase have been used as a model system to optimize
      the experimental conditions in terms of signal intensity and spatial resolution
      as a function of different chemiluminescent substrates such as
      luminol/enhancer/H2O2 and acridancarboxylate ester/H2O2. Localization of oxirane
      beads immobilized acetylcholinesterase has been also used to optimize a system in
      which the detection and localization of the primary enzyme involves two secondary
      enzymes in solution, choline oxidase and horseradish peroxidase, leading to a
      final light emission. Immunoenzymatic reactions for the detection of viral
      antigens and in situ hybridization assays for the detection of viral DNAs
      (cytomegalovirus, herpes simplex virus) have been performed in cells using
      peroxidase-labeled antibodies or cDNA probes and the analytical performance of
      different chemiluminescent substrates for the enzyme has been evaluated. The
      results obtained showed the possibility to sharply image the bioprobes in single
      cells and peroxidase is a suitable label when luminol/H2O2 system is used in
      conjunction with enhancer as in the ECL and SuperSignal Ultra reagents; other
      substrates such as Lumigen PS-3, despite adequate detectability, showed problems
      of localization of the signal as a result of the relatively long half-life of the
      excited emitting species and its diffusion in the chemiluminescent cocktail. The
      system has proven to be highly sensitive, able to perform quantitative analysis,
      and relatively simple.

PMID- 9512773
TI  - Characterization of Helicobacter pylori interactions with sialylglycoconjugates
      using a resonant mirror biosensor.
AB  - A new optical biosensor technique based on the resonant mirror was used to
      characterize Helicobacter pylori strains according to their sialic acid binding,
      demonstrating the suitability of using intact bacteria in real-time measurements
      and classifying strains based on their binding abilities. Results obtained from
      both competition and displacement assays using different glycoconjugates
      confirmed that several, but not all, H.pylori strains express sialic acid-binding
      adhesin(s), specific for alpha-2,3-sialyllactose. The adhesin, removable from the
      bacterial surface by water extraction, is not related to other reported H.pylori
      cell surface proteins with binding ability to sialylated compounds such as
      sialylglycoceramides.

PMID- 9512774
TI  - Nanogram detection of phospholipids on thin-layer chromatograms.
AB  - An extremely sensitive method for the quantitative determination of phospholipids
      on silica gel-precoated thin-layer chromatography plates is reported. The
      procedure is based on the successive application of two lipid spray reagents.
      Firstly, phospholipid chromatograms are sprayed with the lipophilic fluorochrome
      1,6-diphenyl-1,3,5-hexatriene, followed by application of the phosphorus-specific
      molybdenum blue (Dittmer-Lester) reagent. Compared to the single use of the
      respective dyes, the consecutive utilization of both spray reagents resulted in
      an enormous enhancement in sensitivity of at least one order of magnitude. The
      procedure was proved with eight phospholipids of animal origin, and visual
      detection limits of down to 10 ng were achieved. The described technique provides
      a sensitive and specific means for the analysis of phospholipids on the nanogram
      scale by augmenting the molybdenum blue staining with the fluorochrome 1,6
      diphenyl-1,3,5-hexatriene operating as an enhancer.

PMID- 9512775
TI  - From glycine to glutamic acid: analysis of the proton-binding isotherm of
      glutamic acid.
AB  - The process of the analysis of the protonation of glycine is extended to the
      three-site molecule of glutamic acid with its amino and two carboxyl groups.
      Detailed data on the binding of protons to glutamic acid are available not only
      for protonation of the three groups simultaneously but also for derivatives in
      which the alpha and beta carboxyl groups are esterified. These data plus data on
      the protonation of glutaric acid provide the necessary information for a complete
      description of the protonation process with a limited number of reasonable
      assumptions. The assumptions lead to the conclusion that stabilization of the
      molecule of glutamic acid occurs on all steps of the protonation with the
      predominant stabilization occurring in the early steps of the reaction. An
      Appendix is included showing that the experimental data for both glycine and
      glutamic acid can be generated with hypothetical molecules. For glycine,
      identical experimental isotherms can result from protonation of two different
      nitrogen groups as well as two different negative groups. With glutamic acid
      three hypothetical molecules are capable of generating the identical experimental
      isotherms. They are (i) three nitrogen groups, (ii) three negative groups, and
      (iii) two nitrogen groups combined with one negative group. Interpretation of
      binding data requires explicit assumptions defining both the interactions and the
      nature of the binding sites.

PMID- 9512776
TI  - Purification of the alkaloid lycorine and simultaneous analysis of ascorbic acid
      and lycorine by micellar electrokinetic capillary chromatography.
AB  - The pyrrolophenanthridine alkaloid lycorine has frequently been used as a
      specific inhibitor to help elucidate the function of ascorbic acid (vitamin C) in
      a wide range of biological processes. It was recently reported that this function
      can be exercised by inhibiting the activity of L-galactono-1,4-lactone
      dehydrogenase, the terminal enzyme of ascorbic acid biosynthesis, although
      working with the purified enzyme, we have been unable to repeat this result.
      Here, we present a procedure for the purification and analysis of lycorine by
      high-performance liquid chromatography from two Crinum species and describe for
      the first time a method that allows the simultaneous analysis of ascorbic acid
      and lycorine in tissue extracts of Crinum asiaticum by micellar electrokinetic
      chromatography.

PMID- 9512777
TI  - Detection and quantitation of heterotrimeric G proteins by fluorescence resonance
      energy transfer.
AB  - N-Methyl-3'-O-anthranoyl (mant) guanine nucleotide analogs are useful
      environmentally sensitive fluorescent probes for detection of heterotrimeric
      guanine nucleotide binding proteins. The mant derivative of GTP gamma S, mGTP
      gamma S, is synthesized and purified by modification of a method initially
      described by Hiratsuka (1983, Biochim. Biophys. Acta 742, 496-508). The binding
      affinity of mGTP gamma S for G proteins Gi and G(o) is comparable to that of GTP
      gamma S. The rate of binding is determined by the dissociation rate of the
      endogenously bound GDP. The large fluorescence increase observed upon mGTP gamma
      S binding to G protein is due, in part, to resonance energy transfer from
      tryptophans in the G protein to the mant guanine nucleotide. The magnitude of the
      fluorescence increase is dependent upon the concentration of G protein.
      Therefore, mGTP gamma S binding can be used to quantitate and locate G proteins
      during the protein purification process. This method is rapid compared to the
      [35S]GTP gamma S binding assay in that (i) the bound ligand does not need to be
      separated from the free ligand thus avoiding vacuum filtration and (ii) the time
      required to measure fluorescence in each sample is less than that required for
      scintillation counting. In addition, the use of radioactivity can be avoided.
      Thus, the mGTP gamma S binding assay for the detection of Gi and G(o) represents
      a rapid, reliable alternative to assays based on radiolabeled GTP gamma S binding
      or ADP-ribosylation with pertussis toxin.

PMID- 9512778
TI  - Role of hydroxyl radical in silica-induced NF-kappa B activation in macrophages.
AB  - Nuclear transcription factor kappa B (NF-kappa B) is a multiprotein complex that
      regulates a variety of genes important for immunity and inflammation. The present
      study investigates the silica-induced activation of this transcription factor in
      mouse macrophage cell line RAW 264.7 cells, the role of free radical reactions in
      the mechanism of the activation, and its possible inhibition. Tetrandrine, a
      benzylisoquinoline alkaloid, which has been used as an antifibrotic drug to treat
      the lesions of silicosis and has been characterized as a hydroxyl radical (.OH)
      scavenger, inhibited the NF-kappa B activation induced by silica,
      lipopolysaccharide (LPS), and phorbol 12-myristate 13-acetate (PMA). Catalase,
      metal chelator, deferoxamine, and the silanol group (SiOH) blocker, poly(2
      vinylpyridine-N-oxide) (PVPNO), also inhibited silica-induced NF-kappa B
      activation. Electron spin resonance (ESR) spin trapping measurements show that
      both deferoxamine and PVPNO decreased silica-mediated .OH radical generation from
      H2O2. It is shown that Fe(II) and not Fe(III) is able to cause NF-kappa B
      activation. The antioxidant, ascorbate, attenuated the NF-kappa B activation
      induced by silica but not by LPS. The .OH radical scavenger, sodium formate,
      inhibited NF-kappa B activation induced by silica but had only a minor effect on
      NF-kappa B activation induced by LPS. The results indicate that silica-mediated
      free radical generation via the Fenton or Fenton-like reaction (M(n)+ + H2O2-
      >M(n + 1)+ + OH- + .OH) and silanol groups on the silica surface play an
      important role in silica-induced NF-kappa B activation.

PMID- 9512779
TI  - Menetrier's disease presenting with iron deficiency anemia.
AB  - Menetrier's disease (MD) or polyadenomes en nappe is a form of hypertrophic
      gastropathy occurring primarily in middle-aged males. Patients generally present
      clinically with dyspepsia and, on occasion, with hypoproteinemic edema and
      anemia. The latter feature, when combined with the radiographic appearance of the
      stomach in MD, can lend to confusion with carcinoma and malignant lymphoma. To
      illustrate this diagnostic problem, a case is reported of a 41-year-old female
      who initially presented to her family physician with symptoms of easy fatigue and
      dyspnea on exertion and signs of pallor and ankle edema. Pertinent laboratory
      findings included a hemoglobin of 2.8 g/dL, hematocrit of 10.3 percent, mean
      corpuscular volume of 63.4 mu 3, a serum albumin of 2.7 g/dL, and heme positive
      stools. Endoscopic examination revealed a circumferential polypoid mass involving
      the cardia and fundus of the stomach with relative sparing of the antrum. A CT
      scan of the abdomen and pelvis showed a large mass in the stomach which the
      radiologists and gastroenterologists believed probably represented a lymphoma or
      gastric carcinoma. A total gastrectomy specimen exhibited features of MD. Routine
      bright-field microscopy and immunohistochemical reactivity for transforming
      growth factor-alpha confirmed the diagnosis of MD. Moreover, ulceration of the
      tips of some of the hypertrophied gastric folds provided an explantation for the
      iron deficiency anemia. Awareness that MD may present with anemia will help in
      the differential diagnosis with lymphoma and carcinoma.

PMID- 9512780
TI  - Gastrointestinal pathology in sickle cell disease.
AB  - The literature was reviewed to investigate the existence of unique
      gastrointestinal (GI) pathological lesions in sickle-cell disease (SCD). Chole-
      and choledocholithiasis have long been recognized, but bilirubin gallstones can
      occur in any chronic hemolytic anemia. Acute pancreatitis has been reported as a
      possible ischemic consequence of sickling. It is unclear if the hepatic lesions
      of SCD differ from those of any chronically transfused population. Hepatic
      failure has been associated with massive sickling and hyperviscous bile
      ("sludge") has been linked to SCD. Elevated 5'-nucleotidase in the presence of
      elevated aminotransferase may suggest both hepatic and biliary tree involvement
      in a subgroup of patients with SCD. Low levels of the hepatically produced
      coagulation inhibitors, Protein S and Protein C, have been identified in SCD, but
      their precise relation to thrombosis in this instance remains unclear. Finally, a
      syndrome of intracanalicular cholestasis, sinusoidal dilation. Kupffer cell
      hyperplasia, and erythrophagocytosis has been linked to SCD. It has been
      suggested that the use of exchange transfusion prior to liver biopsy in this
      group of pediatric SCD patients may mask the pathophysiological role of sickled
      red blood cells in hepatic dysfunction. With the exception of some of the
      situations cited, it is concluded that most GI lesions in SCD are common to a
      heavily transfused population with chronic hemolytic anemia.

PMID- 9512781
TI  - Chromosome 6 abnormalities associated with prolymphocytic acceleration in chronic
      lymphocytic leukemia.
AB  - Chronic lymphocytic leukemia (CLL) is most characteristically associated with the
      cytogenetic abnormalities +12, 13q14, and 14q32. Recently abnormalities of
      chromosome 6 have been reported in patients with mantle zone lymphoma, CLL mixed
      type, and a CLL variant with larger prolymphocytoid cells in the peripheral
      blood. The purpose of this study was to review the cases of CLL karyotyped at the
      University of Texas M. D. Anderson Cancer Center (UTMDACC) and to determine the
      number and type of chromosome 6 abnormalities. Precisely 830 cases of CLL with
      karyotypes were reviewed. Among these, 257/830 (31 percent) had abnormal
      karyotypes, 56/257 (22 percent) had an abnormality of 6, 18/56 (32 percent) had
      translocations involving 6 and, in most instances, a different chromosome was
      involved, 37/56 (66 percent) had deletion 6 or loss of at least a portion of 6q,
      and 9/56 (16 percent) had an abnormality of 6p. The losses of 6q were in the q13
      to q25 regions. Of these, 13/56 (23.2 percent) of patients with 6q abnormalities
      had > or = 10 percent prolymphocytes (PL) in the bone marrow (BM) and/or
      peripheral blood (PB), 10/56 (17.9 percent) had > or = 10 percent PL in the bone
      marrow, 8/56 (14.3 percent) had > or = 10 percent PL in the peripheral blood, and
      5/56 (9 percent) had > or = 10 percent PL in both (see table I). The 201 CLL
      patients with chromosome abnormalities other than 6 contained 23 with excess PL
      (11.9 percent). A subset of karyotypic changes of 6 associated with increased PL
      is recognizable and may be useful in aiding in clinical diagnosis and therapy.

PMID- 9512782
TI  - Understanding iron absorption and metabolism, aided by studies of
      hemochromatosis.
AB  - Duodenal iron absorption from food is selectively blocked to prevent iron
      intoxication. The prime example of pathologic increase in intestinal iron
      absorption is seen in patients with hemochromatosis. They suffer iron damage to
      the heart, liver, and other tissues resulting in premature death if the iron is
      not removed by vigorous phlebotomy. Examples of overcoming the intestinal barrier
      to iron are alcohol consumption, vitamin preparations with vitamin C, and iron
      consumed by individuals without anemia. Endogenous generation of excess iron by
      hemolysis, owing to abnormal hemoglobin or many transfusions, are not controlled
      by the intestinal barrier.

PMID- 9512783
TI  - Applicability of direct in situ reverse transcription-polymerase chain reaction
      on bone marrow smears.
AB  - In situ reverse transcription (RT)-polymerase chain reaction (PCR) is a promising
      laboratory tool for biomedical investigation at the molecular level in tissues.
      Direct in-cell amplification of the breakpoint cluster region (BCR)-Abelson (ABL)
      fusion transcript of chronic myeloid leukemia (CML) has recently been
      accomplished in Italy using bone marrow mononuclear cell suspensions. The goals
      of this study are to determine if in situ RT-PCR amplification is possible on
      bone marrow spirate smears and to demonstrate any unique factors in this
      procedure. A commercially available method was used because of the existence of
      published protocols for adaptation. Bone marrow (BM) aspirate smears (n = 17)
      from patients with CML in blast crisis (positive case material) or other
      hematological malignancies (negative case material) were evaluated. Satisfactory
      amplification of the BCR-ABL fusion transcript occurred, and distinct blue
      cytoplasmic granules that varied in intensity were found in most CML blasts. The
      negative case materials lacked the specifically amplified granular signals.
      Overall signal strength and backgrounds were readily affected by the quality of
      the specimen as well as by changes in assay parameters. In conclusion, the direct
      in situ RT-PCR technique is applicable for bone marrow aspirate smear evaluation.
      However, it remains an investigative tool until optimization for sensitivity,
      specificity, and accuracy can be achieved.

PMID- 9512784
TI  - Effects of metallic antioxidants on cadmium-catalyzed peroxidation of arachidonic
      acid.
AB  - In the present study, the reaction mixtures (cadmium chloride with arachidonic
      acid) were preincubated at 37 degrees C for 24 h prior to the measurement of
      malondialdehyde (MDA) by high performance liquid chromatography (HPLC). The
      cadmium-catalyzed reactions were also compared to those in the presence of
      selenium (Se), zinc (Zn) or germanium (Ge), metallic antioxidants. Our results
      showed that the toxic effects of cadmium cause lipid peroxidation of arachidonic
      acid by the catalytic process. The addition of metallic antioxidants to the
      reaction mixtures, might be useful in protecting against Cd-induced lipid
      peroxidation.

PMID- 9512785
TI  - Interphase fluorescence in situ hybridization analysis: a study using centromeric
      probes 7, 8, and 12.
AB  - Interphase fluorescence in situ hybridization (I-FISH) is a useful technique for
      detecting chromosomal numerical abnormalities in tumors and is gaining acceptance
      as a tool in cytogenetics and clinical diagnoses. Performance and quality control
      information about commercial products are necessary in order to implement an
      individual FISH probe as a routine clinical laboratory test. Interphase FISH
      analysis was performed with three commercially available alpha-satellite
      chromosome-specific DNA centromeric probes (D7Z1/D7Z2; D8Z2; and D12Z3) on bone
      marrow material prepared for conventional cytogenetic analysis. The results were
      interpreted following enumeration of the signals in 500 interphase nuclei each by
      two different observers. A mean of 93.92 percent (+/- 1.3 percent, 1 SD) was
      found for chromosome 7; a mean of 93.91 percent (+/- 1.5 percent, 1 SD) was found
      for chromosome 8, and a mean of 92.85 percent (+/- 1.4 percent, 1 SD) was found
      for chromosome 12. The results of the study demonstrated that I-FISH using
      chromosome centromeric probe(s) is a reliable, reproducible, and accurate
      technique. This technique can be integrated into routine clinical practice with
      proper quality control protocols.

PMID- 9512786
TI  - Gonadotropin releasing hormone does not affect steroidogenesis in JEG-3 cells.
AB  - Gonadotropin releasing hormone (GnRH) affects ovarian and testicular
      steroidogenesis, is produced by the placenta, and increases chorionic
      gonadotropin (hCG) production in preterm placenta. It was hypothesized that GnRH
      might also regulate placental synthesis of progesterone (P) and estradiol (E2)
      and the effects were studied of GnRH and the [D-Trp6]-LH-RH analog on the
      production of P, E2, and hCG by JEG-3 choriocarcinoma cells. Neither GnRH nor [D
      Trp6]-LH-RH had any effect on the production of P, E2 or hCG. Our findings are
      similar to a previous observation which showed GnRH did not increase hCG in term
      placenta, but differed from preterm placenta in which GnRH increased hCG. This
      suggests there could be maturational changes in the placental response to GnRH
      and that JEG-3 cells more closely resemble term placenta. It is our conclusion
      that although GnRH and the GnRH receptor are found in the placenta, GnRH might
      have no effect on steroid hormone synthesis near term.

PMID- 9512787
TI  - Small vestibular schwannomas in the elderly: a management dilemma.
AB  - Small vestibular schwannomas were diagnosed in two elderly patients and, for
      different reasons, a policy of watch and wait was instituted. One was reliable in
      attending for follow-up and lived for over 20 years without surgical
      intervention. The other was unreliable in follow-up, there was an unexpected and
      undetected acceleration of the growth rate and urgent surgery became imperative
      at the age of 77 years. This provided to be unsuccessful. A watch and wait policy
      is acceptable in the elderly but only if the patient can be relied upon to co
      operate in follow-up attendance and imaging.

PMID- 9512788
TI  - Purified streptococcal cell wall (PG-APS) causes experimental otitis media.
AB  - Purified peptidoglycan-polysaccharide from Group A Streptococcus pyogenes cell
      wall (PG-APS) was prepared under sterile, pyrogen-free conditions and injected
      percutaneously into the middle ear cavities (MEC) of groups of gerbils. Each
      group was observed otoscopically at 1, 2, 5, 7, 9, 12 and 14 days. Histologic
      specimens were obtained from each group at 2, 5, 7, 9 and 14 days.
      Histologically, PG-APS produced mild, acute inflammation during the first 3 days
      and mild to moderate inflammation with features of both acute and chronic
      pathology from days 5 through 9. An early response by plasma cells and
      macrophages was seen. Most animals had recovered with minor sequelae by day 14.
      Challenge intraperitoneally with 20 micrograms of PG-APS at 14 days following MEC
      injection of PG-APS did not exacerbate the middle ear inflammation. Five
      chinchillas, tested for comparison, responded similarly to PG-APS.

PMID- 9512789
TI  - An electrophysiologic study of the guinea pig inner ear following low pressure
      barotrauma.
AB  - We examined electrophysiologic and morphologic changes following low pressure
      barotrauma in 25 guinea pigs. Compound action potentials (CAPs), cochlear
      microphonics (CMs), and transiently evoked otoacoustic emissions (TEOAEs) were
      elicited by tone bursts (1, 2, 4 and 8 kHz) or non-linear clicks immediately
      following barotrauma. CAP threshold elevations were observed in 19 out of 25
      cochleas, mainly at lower stimulus frequencies. Furthermore, CM and TEOAE
      thresholds were significantly increased, while CAP and CM amplitudes demonstrated
      reductions at all stimulus frequencies and intensities. CAP N1 latencies
      exhibited slight elongations at all stimulus frequencies and intensities. The
      regression coefficient between the mean CAP thresholds of four stimulus
      frequencies and TEOAE thresholds was statistically significant. Scanning electron
      microscopy (SEM) study of six electrophysiologically abnormal cochleas revealed
      stereocilia morphology in four, but no changes in two. We hypothesize that low
      pressure barotrauma can injure inner ear hair cells through an early threshold
      shift secondary to dislocation of the basement membrane.

PMID- 9512790
TI  - Long-term hearing status after radiotherapy for nasopharyngeal carcinoma.
AB  - This paper evaluates the hearing status in the long-term, of patients who have
      had radiotherapy for nasopharyngeal carcinoma (NPC) and also discusses the
      hearing losses from a disability point of view, which takes into account binaural
      hearing. Forty patients who have had NPC successfully treated by a single radical
      course of radiotherapy of 70-80 Gy were studied at 2-12 years (mean 6.2 years)
      after radiotherapy. Each patient was examined clinically and with a pure-tone
      audiogram. Averaged hearing thresholds over 0.5, 1.0, 2.0 and 4.0 kHz were
      evaluated and a value > 30 dB was considered abnormal. The findings were compared
      with age-matched controls. The median hearing threshold for each ear in NPC
      patients was found to be 31.9 dB (range 10.0-86.3 dB) and that for controls 17.5
      dB (7.5-38.8 dB) (P < 0.0005, Wilcoxon's matched pairs test). In NPC patients, 44
      ears (55.0%) had abnormal hearing, of which 17 (21.3%), 5 (6.3%) and 22 (27.5%)
      ears had predominantly sensori-neural, conductive and mixed hearing losses,
      respectively. Nineteen ears had middle ear effusions, accounting for the majority
      of mixed and conductive hearing losses. In terms of individual patients, 8
      (20.0%) and 18 (45.0%) patients had abnormal hearing in one year (monaural
      hearing disability) and both ears (binaural hearing disability), respectively. In
      conclusion, a substantial proportion of patients who have had radiotherapy for
      NPC, have hearing disability in the long-term, as compared to normal controls.

PMID- 9512791
TI  - Inflammatory mediators and otitis media with effusion. An experimental approach
      using cell culture.
AB  - Otitis media with effusion is characterized by the presence of an inflammatory
      cellular infiltrate of the submucosa and a poor ventilation of the middle ear.
      This result in hypersecretion of mucus and alteration of the mucociliary
      clearance, which produce accumulation of fluid and cellular debris in the middle
      ear. The aim of this work was to investigate whether inflammatory mediators such
      as prostaglandins and oxygen metabolites modulate the absorptive function of the
      middle ear epithelium. The data we present demonstrated that: (i) among
      prostanoids, only prostaglandin E2 modulated the rate of sodium transport; (ii)
      oxidants had a stimulatory effect on ion transport; (iii) the role of reactive
      oxygen species was mediated by prostaglandin E2. This process might be involved
      in the impairment of the mucociliary clearance.

PMID- 9512792
TI  - Psychosomatic aspects of patients complaining of dizziness or vertigo with
      orthostatic dysregulation.
AB  - Eighty-five patients (26 males and 59 females) with orthostatic dysregulation who
      visited our clinic complaining of dizziness or vertigo between December, 1990 and
      August, 1996 were analyzed using the Japanese Edition Cornell Medical Index
      Health Questionnaire and the Yatabe-Guilford Personality Test. The condition of
      OD was most commonly noted in 29 patients (34.1%) with dizziness or vertigo of
      indeterminate etiology, followed by in 14 (16.5%) with Meniere's disease, in ten
      (11.8%) with hypotension and CNS disorder each, and in 22 (25.9%) with other
      disorders. The percentage classed as Type III (possible neurotic) or Type IV
      (probable neurotic), was 46.1% in males and 47.4% in females. The percentage
      classed as Type B or Type E, suggestive of emotional or psychological
      disturbance, was 38.5% in males and 37.3% in females. There was good correlation
      between the Japanese Edition Cornell Medical Index-Health Questionnaire and the
      Yatabe-Guilford Personality Test results as to psychosomatic aspects. We conclude
      that, in the treatment of patients with orthostatic dysregulation, it is
      necessary to consider both physical and psychological aspects of the condition.

PMID- 9512793
TI  - Intranasal endoscopic excision of a juvenile angiofibroma.
AB  - Intranasal endoscopic excision of a juvenile nasopharyngeal angiofibroma (JNA)
      was performed in a 13 year old white male. The patient remains disease-free 24
      months after the operation. Although endoscopic surgical techniques have been
      applied to the therapy of some benign nasal tumors, such as inverting papilloma,
      endoscopic resection of a documented JNA has not been previously reported. This
      technique is reserved for tumors which are limited to the nasal cavity and
      paranasal sinuses with minimal extension into the pterygopalatine fossa.

PMID- 9512795
TI  - Use of iliac bone graft for saddle nose deformity.
AB  - The reconstruction of the saddle nose deformity presents an arduous task for the
      reconstructive surgeon. A large variety of graft materials have been used for
      augmentation rhinoplasty. The modern trend is to prefer autologous material.
      Iliac bone grafts are extremely suitable for augmenting moderate to severe saddle
      nose deformity. In our study, autogenous iliac bone grafts were used in the nasal
      reconstruction of 14 patients. The follow up has been from 1-4 years, with no
      significant resorption noted during that time. Complication was limited to one
      hematoma on the donor side.

PMID- 9512794
TI  - Correlation between nasal obstruction symptoms and objective parameters of
      acoustic rhinometry and rhinomanometry.
AB  - Acoustic rhinometry and rhinomanometry have been used to assess nasal airway
      patency objectively. We compared nasal obstruction symptoms before and after
      decongestion with several parameters of these objective tests. The patients
      assessed their nasal obstruction using a visual analogue scale (VAS). Cross
      sectional areas and nasal resistance were measured by acoustic rhinometry and
      rhinomanometry before and after topical application of 1% phenylephrine solution
      in 32 patients with nasal obstruction symptoms. There was no significant
      correlation between the difference in the VAS and the difference in nasal
      resistance. There was also no significant correlation between the difference in
      the VAS and minimal cross-sectional area and cross-sectional areas at 3.3 cm
      (CA3.3), CA4.0 and CA6.4 from the nosepiece both in the wide and narrow sides and
      in both nasal cavities before and after nasal decongestion. It is concluded that
      rhinomanometry and acoustic rhinometry may have no diagnostic value in estimating
      the severity of nasal obstruction symptoms.

PMID- 9512796
TI  - Effectiveness of classical chordectomy in the treatment of cancer of the glottis.
AB  - From 1980 to 1992, 85 patients diagnosed with tumour of the glottis, localized
      exclusively in the vocal cord area, had undergone surgery. A 90% 5-year survival
      rate without recurrences had been obtained. Taking into account the cases of life
      saving surgery, the percentage of the 5-year survivals amounted to 94%.
      Considerably better results were obtained by the excision of the entire vocal
      cord and not just one of its sections (1/2, 2/3 etc.). The degree of deformation
      of the voice following chordectomy was assessed by means of acoustic and
      laryngographic methods (Laryngograph Processor PCLX). A 13% rate of irregularity
      in the functioning of the neoglottis, following surgery, was observed. The Jitter
      Shimmer co-efficients were established. The results of the deformation of the
      voice following chordectomy were presented on the J-S scale and compared with
      other partial surgeries performed on patients with tumours of the glottis. All of
      the acoustic and laryngographic findings were presented in the from of mean
      values most representative of chordectomy.

PMID- 9512797
TI  - Ultrasound in the diagnosis of cervical tuberculous adenitis.
AB  - Ultrasound (US) of cervical tuberculous adenitis (CTA) was demonstrated to
      produce a characteristic pattern of the affected nodes in the majority of the
      patients in this study. The contribution of US to the diagnosis and assessment of
      CTA is evaluated. It is concluded that, since the other diagnostic tests for CTA
      are not reliable and/or time-consuming, the demonstration of nodal
      calcifications, conglomerate nodal masses and spread into the subcutaneous
      tissues at US in patients with elusive cervical masses may result in earlier
      recognition of CTA.

PMID- 9512798
TI  - Research advances for cochlear implants.
AB  - Considerable progress has been made with speech processing for multiple-channel
      cochlear implants, with a mean open-set CNC word score of 40% for electrical
      stimulation alone for the Nucleus SPEAK strategy. Further advances should be
      achieved through the following: beam-forming dual microphone systems for hearing
      in noise; better reproduction of the coding of sound frequencies; and taking
      advantage of plasticity in the central auditory pathways in young children. The
      reproduction of frequency coding will be facilitated with speech processors such
      as the Nucleus 24 system which can provide higher stimulus rates, and a new
      generation of electrode arrays where a greater number of electrodes lie close to
      the spiral ganglion cells.

PMID- 9512799
TI  - Lymphoma of the tympanic membrane in acquired immunodeficiency syndrome.
AB  - Lymphoproliferative disease is more common in the immunocompromised host and can
      occur at unusual sites. Lymphomas of the temporal bone are rare. We present the
      first case of a large B-cell Lymphoma of the tympanic membrane in a patient with
      acquired immunodeficiency syndrome. The tympanic membrane is a site rich with
      antigen-presenting dendritic cells that may play an etiologic role in neoplastic
      transformation at this site. The staging, treatment and prognosis of an
      immunocompromised host afflicted with lymphoma is discussed. Future directions in
      improving survival include better therapy for the primary viral infection and
      less toxic therapy for the lymphoma.

PMID- 9512800
TI  - Cochlear otosclerosis 30 years after stapedectomy confirmed by CT, MRI.
AB  - A 64-year-old Japanese male patient, status post-stapedectomy, presented with
      progressive, bilateral SNHL of 30 years' duration. CT showed extensive
      demineralization of the otic capsule, suggestive of otospongiotic change in both
      ears. There were no hyperostotic lesions found, which would have been suggestive
      of otosclerotic change. MRI showed a morphologically intact membranous labyrinth
      in both ears, with no obstruction of the cochlear lumen. It was concluded that
      the patient has progressive otospongiotic change of the otic capsule, but no
      otosclerotic change.

PMID- 9512801
TI  - Six primary squamous cell carcinomas of the head and neck.
AB  - The chronic irritation to mucosa of the head and neck area by carcinogen,
      commonly stemming from heavy usage of betel nuts, tobacco and alcohol, leads to
      dysplastic mucosal changes and eventually, multiple primary squamous cell
      carcinomas. With improvements in locoregional control, the problem of multiple
      primary malignancies of the head and neck is becoming apparent. We reported a
      unique case of six primary squamous cell carcinomas in the head and neck area. We
      attribute the success of controlling cancer in this patient to our alert attitude
      and prompt management. Surgery remains one of the best options in treating
      multiple head and neck malignancies, as surgery offers an effective, quick and
      low morbidity approach, and does not take the chance of inducing another cancer.

PMID- 9512802
TI  - Biliary atresia and biliary cysts.
AB  - The authors present a review of the classification, aetiology, presentation,
      treatment and long-term outcome of children and adults with biliary atresia and
      choledochal cyst disease. Biliary atresia should be suspected in any infant with
      jaundice beyond the second week of life. Although the aetiology and pathogenesis
      remain unclear, early management with portoenterostomy has significantly improved
      the course of this disease. Recent advances in immunosuppression have made liver
      transplantation a valuable and necessary adjunct to biliary bypass. With
      choledochal cyst disease, adults, unlike children, often present with acute
      biliary tract symptoms or pancreatitis. The treatment of choice remains
      extrahepatic cyst excision and biliary bypass. This treatment has excellent long
      term results that minimize the development of malignancy.

PMID- 9512803
TI  - Cholelithiasis and acute cholecystitis.
AB  - Although much is still to be learned about the pathogenesis of cholelithiasis,
      recent investigations have greatly advanced our knowledge regarding the
      mechanisms of cholesterol supersaturation and nucleation. Laparoscopic
      cholecystectomy has lessened the usual peri-operative morbidity of
      cholecystectomy, but is associated with a higher bile duct injury rate. Acute
      cholecystitis, the commonest complication of cholelithiasis, is a chemical
      inflammation usually requiring cystic duct obstruction and supersaturated bile.
      The treatment of this condition in the laparoscopic era is controversial. Early
      operation may lessen hospital stay but an increased risk of biliary injury has
      been reported.

PMID- 9512804
TI  - Choledocholithiasis and gallstone pancreatitis.
AB  - Gallstones are commonly found within the main bile duct (MBD) of patients
      undergoing cholecystectomy. Retained MBD stones are a common cause of obstructive
      symptoms and complications. Endoscopic retrograde cholangiopancreatography (ERCP)
      and sphincterotomy (ES) is the recommended modality for both the detection of
      such stones and their extraction. Recent trials of ERCP in conjunction with
      laparoscopic cholecystectomy suggest that it should be reserved for use post
      operatively. Gallstones within the MBD are the most common single cause of acute
      pancreatitis. Initial treatment is supportive, although new agents designed to
      suppress the systemic inflammatory response are under development and have proved
      beneficial in clinical trials. Severe cases should be treated with systemic
      antibiotics and early removal of the obstructing stones by ERCP and ES.
      Prophylactic cholecystectomy is recommended to prevent further attacks of
      gallstone pancreatitis.

PMID- 9512805
TI  - Hepatolithiasis and biliary parasites.
AB  - Hepatolithiasis, or the presence of intrahepatic stones, is prevalent in East
      Asia and is characterized by the finding of stones within the intrahepatic bile
      ducts proximal to the confluence of the right and left hepatic ducts. Bile stasis
      and bacterial infection have been incriminated as the major aetiopathogenic
      factors. Clinical features include recurrent pyogenic cholangitis, multiple liver
      abscesses, secondary biliary cirrhosis and cholangiocarcinoma. The goals of
      management include accurate localization of pathologies, control of biliary
      sepsis and the elimination of stones and stasis. Ultrasonography, computed
      tomography and direct cholangiography complement each other in defining the
      stones, strictures and degree of liver damage. Non-operative biliary
      decompression by endoscopy and interventional radiology is effective in
      controlling the infection, but surgery remains the mainstay for the treatment of
      stones and strictures. Intra-operative ultrasound and flexible choledochoscopy,
      combined with percutaneous transhepatic cholangioscopy and intraductal
      lithotripsy, facilitate stone removal. Balloon dilatation and biliary stenting
      serve to open the bile duct strictures. The creation of a hepaticocutaneous
      jejunostomy after conventional surgery allows atraumatic access to the biliary
      system for the removal of recurrent stones. The management of biliary parasites
      begins with conservative measures, including analgesics and anti-helminthic
      therapy. In refractory cases or patients with acute cholangitis, endoscopic
      biliary drainage and the extraction of worms may be necessary. Improvement in
      sanitation plays a crucial role in the epidemiological control of these biliary
      diseases.

PMID- 9512806
TI  - Biliary infection.
AB  - Biliary infections are common conditions that can be life threatening. In the
      past, many of these conditions mandated emergency surgery, but advances in
      endoscopic and radiological techniques have allowed some of these to be managed
      in a minimally invasive fashion. Acute cholangitis is caused by infection in an
      obstructed biliary tree. Endoscopic drainage, together with broad-spectrum
      antibiotics, has replaced emergency common duct exploration and T-tube drainage
      as standard treatment. Oriental cholangitis, sclerosing cholangitis and AIDS
      related cholangitis are some of the variants of cholangitis. Pyogenic liver
      abscesses complicating cholangitis can be managed by radiological percutaneous
      drainage. Close collaboration between surgeons, endoscopists and radiologists is
      the key to success in managing biliary infections.

PMID- 9512807
TI  - Biliary motility disorders.
AB  - Disordered motility of the biliary tract may be associated with the aetiology of
      common biliary tract conditions, such as gallstones. In this instance, treatment
      of the gallstone disease alleviates symptoms in the majority of patients.
      However, in up to 10% of patients, biliary motility disorders may present in the
      absence of gallstones or in patients after cholecystectomy. Gallbladder
      dyskinesia results in biliary-type pain. This abnormality may be objectively
      identified using the radionuclide gallbladder ejection fraction. The majority of
      patients with an abnormal test are improved or cured following cholecystectomy.
      Sphincter of Oddi dysfunction presents with either recurrent biliary-type pain or
      recurrent pancreatitis. Manometry of the sphincter of Oddi objectively identifies
      patients with manometric stenosis. The majority of these patients are improved or
      cured following division of the sphincter of Oddi.

PMID- 9512808
TI  - Biliary fistulae and haemorrhage.
AB  - Percutaneous biliary drainage is the most common aetiology of haemobilia. Bile
      duct fistulae can also arise from the hepatic or portal vein, most commonly as a
      result of trauma. Percutaneous methods for treating haemobilia from all these
      sources are discussed in detail.

PMID- 9512809
TI  - Benign post-operative bile duct strictures.
AB  - The vast majority of post-operative bile duct strictures occur following
      cholecystectomy, these injuries having been seen at an increased frequency since
      the introduction of laparoscopic cholecystectomy. Bile duct injuries usually
      present early in the post-operative period, obstructive jaundice or evidence of a
      bile leak being the most common mode of presentation. In patients presenting with
      a post-operative bile duct stricture months to years after surgery, cholangitis
      is the most common symptom. The 'gold standard' for the diagnosis of bile duct
      strictures is cholangiography. Percutaneous transhepatic cholangiography is
      generally more valuable than endoscopic retrograde cholangiography in that it
      defines the anatomy of the proximal biliary tree that is to be used in surgical
      reconstruction. The most commonly employed surgical procedure with the best
      overall results for the treatment of bile duct stricture is a Roux-en-Y
      hepaticojejunostomy. The results of the surgical repair of bile duct strictures
      are excellent, long-term success rates being in excess of 80% in most series.
      Recent data have suggested that, at intermediate follow-up of approximately 3
      years, an excellent outcome can be obtained following repair of bile duct
      injuries after laparoscopic cholecystectomy. Percutaneous and endoscopic
      techniques for the dilatation of bile duct strictures can be useful adjuncts to
      the management of bile duct strictures if the anatomical situation and clinical
      scenario favour this approach. In selected patients, the results of both
      endoscopic and percutaneous dilatation are comparable to those of surgical
      reconstruction.

PMID- 9512810
TI  - Sclerosing cholangitis.
AB  - Primary sclerosing cholangitis (PSC) is a chronic, progressive cholestatic liver
      disease whose aetiopathogenesis is unknown. PSC is frequently associated with
      inflammatory bowel disease, in particular chronic ulcerative colitis, is most
      commonly observed in young males and is clinically characterized by fatigue,
      pruritus and jaundice. The diagnosis is supported by a cholestatic biochemical
      profile and histological abnormalities, and confirmed by visualization of an
      abnormal biliary tree. The natural history of the disease is currently being
      evaluated but is generally recognized to be slowly progressive, leading to
      complications of chronic cholestasis, portal hypertension and biliary cirrhosis.
      There is no specific medical treatment, and orthotopic liver transplantation
      remains the only definitive treatment for patients with end-stage PSC. A more
      rational approach to medical therapy will ensue upon a better understanding of
      the aetiopathogenesis of this disease.

PMID- 9512811
TI  - Biliary malignancies.
AB  - Biliary malignancies, including cancers of the intrahepatic and extrahepatic bile
      ducts, gallbladder and ampulla, should be considered in the differential
      diagnosis of patients with obstructive jaundice. Cancers of the intrahepatic bile
      ducts and ampulla are managed as liver and peri-ampullary tumours respectively.
      Extrahepatic bile duct cancers are diagnosed by cholangiography and evaluated for
      resectability by imaging and angiography. Vascular infiltration is the main
      contra-indication for resection, which may also involve the liver. Every attempt
      must be made to achieve curative resection, but local resection may be justified
      even if non-curative. Gallbladder cancers are usually advanced at the time of
      diagnosis and are unresectable--surgical palliation improves the quality of life
      by relieving biliary and gastric outlet obstruction. Long-term survival is
      possible after curative resection in early lesions that are usually diagnosed as
      an incidental finding after cholecystectomy for presumed gallstone disease. The
      role of adjuvant therapy in biliary malignancies needs further evaluation.

PMID- 9512813
TI  - Inflammatory events at the blood brain barrier: regulation of adhesion molecules,
      cytokines, and chemokines by reactive nitrogen and oxygen species.
AB  - Recruitment of inflammatory cells into the CNS during pathological processes
      associated with neurodegeneration, trauma, autoimmune disease, and infection
      involves the generation of signaling molecules that are both cell-associated and
      soluble. Alteration in the permeability of the blood brain barrier, adhesion of
      blood-borne leukocytes to cerebral vessels, activation of chemoattractants and
      their receptors, and migration of inflammatory cells into the CNS are events that
      have been proposed to be regulated by cytokines and reactive oxygen and nitrogen
      species. In this review we propose associative connections between these events
      and the molecules involved as they may relate to CNS inflammation, placing
      illustrative emphasis on multiple sclerosis and the animal model for MS,
      experimental allergic encephalomyelitis.

PMID- 9512814
TI  - Immunohistochemical examination of intracerebral T cell recruitment and adhesion
      molecule induction in herpes simplex virus-infected mice.
AB  - Herpes simplex virus type 1 (HSV-1) infection in the nervous system is tightly
      controlled by the T-cell-mediated response. This report describes the temporal
      relationships among HSV-1 infection, intracerebral adhesion molecule induction,
      and T cell migration in intravitreally inoculated mice. HSV-1 immunoreactivity,
      initially detected at 3 days, increased in area and intensity in the superior
      colliculus, oculomotor nucleus, and geniculate through 5 days. By 6 days, HSV-1
      was nearly undetectable in the same regions and the mice survive the infection.
      At the peak of HSV-1 immunoreactivity, ICAM-1 and VCAM-1 were strongly expressed
      in all infected brain regions. Additionally, in these region a few CD4+ and CD8+
      T cells were detected. The heaviest T cell migration and adhesion molecule
      expression occurred at 6 days, coinciding with the decrease in HSV-1
      immunoreactivity. However, in SCID and athymic mice, HSV-1 was not cleared from
      the brain and the mice died. Together, these data suggest that HSV-1 infection of
      the brain is followed by adhesion molecule induction in and T cell extravasation
      into the infected brain regions. Most importantly, an efficient T cell response
      was required to eradicate infectious HSV-1 from the brain.

PMID- 9512815
TI  - ICAM-1 induction in the mouse CNS following irradiation.
AB  - Injury to the central nervous system (CNS) results in inflammation, increased
      trafficking of leukocytes into the CNS, induction of cytokines, and exacerbation
      of the primary injury. The increased trafficking of neutrophils into the CNS has
      been described following a number of injury models including stab, stroke, and
      excitotoxin-induced injury. This enhanced trafficking has largely been ascribed
      to the adhesion molecule intercellular adhesion molecule-1 (ICAM-1, CD54). In the
      current study, we wished to determine if the inflammation caused by irradiation
      of the CNS resulted in a similar induction of ICAM-1. C3H/HeJ mice were
      irradiated using gamma irradiation aimed over the right cerebral hemisphere. The
      relative induction of ICAM-1 mRNA levels was determined using quantitative RT-PCR
      6 hours following irradiation with either 0, 5, 15, 25 or 35 Gy. ICAM-1 message
      was seen to exhibit a normal dose response curve with increasing mRNA levels seen
      at 15 Gy and higher. To determine the cellular distribution of the ICAM-1 protein
      following irradiation, mice were sacrificed at 4 hrs, 24 hrs, 48 hrs and 7 days
      following 25 Gy irradiation and the tissue was processed for ICAM-1
      immunocytochemistry. ICAM-1 staining was seen to increase in both endothelial
      cells and astrocytes beginning as early as 4 hrs. The staining intensity
      continued to increase throughout the 7 day period observed. Together, these
      results suggest that irradiation of the CNS causes a rapid induction of both ICAM
      1 mRNA and protein. This suggests that increased leukocyte trafficking into the
      CNS may exacerbate the inflammation induced by radiation injury.

PMID- 9512816
TI  - Acute stress enhances while chronic stress suppresses cell-mediated immunity in
      vivo: a potential role for leukocyte trafficking.
AB  - Delayed type hypersensitivity (DTH) reactions are antigen-specific, cell-mediated
      immune responses which, depending on the antigen involved, mediate beneficial
      (resistance to viruses, bacteria, fungi, and certain tumors) or harmful (allergic
      dermatitis, autoimmunity) aspects of immune function. We have shown that acute
      stress administered immediately before antigenic challenge results in a
      significant enhancement of a skin DTH response in rats. A stress-induced
      trafficking or redeployment of leukocytes to the skin may be one of the factors
      mediating this immunoenhancement. Here we investigate the effects of varying the
      duration, intensity, and chronicity of stress on the DTH response and on changes
      in blood leukocyte distribution and glucocorticoid levels. Acute stress
      administered for 2 h prior to antigenic challenge, significantly enhanced the DTH
      response. Increasing the duration of stress from 2 h to 5 h produced the same
      magnitude enhancement in cutaneous DTH. Moreover, increasing the intensity of
      acute stress produced a significantly larger enhancement of the DTH response
      which was accompanied by increasing magnitudes of leukocyte redeployment. In
      contrast, chronic stress suppressed the DTH response when it was administered for
      3 weeks before sensitization and either discontinued upon sensitization, or
      continued an additional week until challenge, or extended for one week after
      challenge. The stress-induced redeployment of peripheral blood lymphocytes was
      attenuated with increasing exposure to chronic stress and correlated with
      attenuated glucocorticoid responsivity. These results suggest that stress-induced
      alterations in lymphocyte redeployment may play an important role in mediating
      the bi-directional effects of acute versus chronic stress on cell-mediated
      immunity in vivo.

PMID- 9512818
TI  - Adrenergic control of natural killer cell circulation and adhesion.
AB  - Natural killer (NK) cell circulation is subject to adrenergic regulation. Exactly
      how NK cells are released into the circulation is unknown. In an attempt to
      identify some of the mechanisms, the present report focuses on aspects of
      adhesion regulation of NK cells. Results demonstrate that interactions between NK
      and endothelial cells (EC) in vitro can be reduced by beta 2-adrenoceptor
      stimulation for as long as the receptor stimulation occurs. The level of soluble
      adhesion molecules (sICAM-1, sE-selectin, sVCAM-1) in vivo remained unchanged
      during adrenaline infusion. In vitro analyses further reveal the requirement for
      Ca2+/Mg2+ in NK-EC adhesion. Blocking studies indicate the involvement of several
      members of the beta 1(CD29)- and beta 2(CD18)-integrin family, reducing NK cell
      adhesion by 28 to 39%. Stimulation of beta 2-adrenoceptors in the presence of
      these blocking antibodies further reduced NK adhesion by an average of 22%.
      Analysis of NK cell adhesion to various extracellular matrix components
      demonstrates significant NK cell adhesion to fibronectin but much less to laminin
      or collagens I and IV. NK cell adhesion to fibronectin was reduced by 50% upon
      beta 2-adrenoceptor stimulation, independent of the VLA-4/VLA-5 binding site on
      fibronectin. Together these results contribute to understanding the influences of
      beta-adrenoceptor stimulation on NK cell circulation and adhesion.

PMID- 9512817
TI  - Catecholamine modulation of lymphocyte homing to lymphoid tissues.
AB  - Lymphocyte migration is an essential process for immune surveillance and for
      promoting cell-cell interactions necessary to generate an immune response. This
      report examined whether catecholamine prestimulation would alter the pattern of
      lymphocyte homing to spleen and lymph nodes in mice as determined by tracking
      fluorescently labeled cells. The results of cell sorter analysis showed that
      catecholamine-pretreated cells had increased accumulation in spleen and lymph
      nodes 1 and 2 h after i.v. injection. In addition, microscopic analysis showed
      that labeled cells migrated from the splenic red pulp to T-cell regions of the
      white pulp over a 2-h time course. Within the lymph nodes, labeled cells
      localized predominantly to the pericortex. Additional studies examined the
      migration of lymphocytes to lymphoid tissues of NGF-transgenic mice that have
      sympathetic hyperinnervation of spleen and peripheral lymph nodes. In contrast to
      the studies above, migration of T-cells from control mice to lymphoid tissues of
      the hyperinnervated mice was not different than that in control mice in most
      tissues. The accumulation of lymphocytes in lymphoid tissues is a balance between
      the influx of newly migrated cells and efflux back into the circulation. The
      studies in this report lend support to other studies showing catecholamine
      modulation of lymphocyte migration and homing, but it is a complex process about
      which much has yet to be understood.

PMID- 9512819
TI  - L-selectin expression affects T-cell circulation following isoproterenol infusion
      in humans.
AB  - beta-Adrenergic receptor agonists have been shown to affect leukocyte migration.
      This study examined the expression of cellular adhesion molecules on lymphocyte,
      monocyte, and granulocyte distribution following an infusion of isoproterenol (20
      and 40 ng/kg/min for 15 min each) in 12 healthy subjects. Leukocyte populations
      and adhesion molecule expression were determined via flow cytometry.
      Isoproterenol led to an expected lymphocytosis and leukocytosis. L-selectin
      expression varied across leukocytes and influenced cell trafficking in response
      to isoproterenol. Approximately 60% of CD8+ T-cells expressed L-selectin
      (CD8+CD62L+) and these cells showed no appreciable response to isoproterenol. In
      contrast, CD8+CD62L- cells showed a robust increase in number and distribution of
      approximately 100% over baseline (p's < .001). Across CD4+ T-helpers, L-selectin
      was expressed on approximately 86% of cells. CD4+CD62L+ cells decreased in number
      and distribution (p's < .001) with isoproterenol, while CD4+CD62L- cells showed a
      modest increase (p's < or = .05). In contrast to lymphocytes, nearly all
      monocytes and granulocytes expressed L-selectin; these cells increased and
      decreased respectively in response to isoproterenol (p's < or = .05). CD11a (the
      beta 2-integrin LFA-1) was expressed on > 95% of all leukocytes and these data
      were thus similar to the overall leukocytosis data. CD54 (ICAM-1) was expressed
      on approximately 60% of mixed lymphocytes and was unchanged in response to
      isoproterenol. The findings indicate that L-selectin expression influences T-cell
      trafficking in response to beta-adrenergic stimulation and help further
      illuminate catecholamine-mediated sympathetic and immune interactions.

PMID- 9512820
TI  - Dynamic exercise leads to an increase in circulating ICAM-1: further evidence for
      adrenergic modulation of cell adhesion.
AB  - Acute mental and physical stress lead to a marked lymphocytosis, with circulating
      natural killer cell numbers showing the most prominent increase. Many studies
      have linked these acute stress effects on lymphocytes with an increase in
      catecholamine levels. However, the molecular mechanisms which mediate this
      redistribution of lymphocytes from lymphocyte reservoirs into the circulation
      remain unknown. We hypothesized that this form of lymphocytosis was in part due
      to shedding of cell adhesion molecules from the cell surface and a subsequent
      detachment of lymphocytes adhering to the vascular endothelium in lymphocyte
      reservoirs. In this study, healthy human volunteers (n = 12) were exercised on a
      treadmill until exhaustion. The circulating levels of the soluble cell adhesion
      molecules ICAM-1 and E-Selectin were determined by ELISA. The subjects were then
      randomly assigned to treatment with either propranolol or metoprolol and repeated
      the exercise protocol after 1 week of treatment. Prior to drug treatment, soluble
      ICAM-1 levels rose from 258 +/- 19 to 321 +/- 28 ng/ml following exercise and
      returned to approximate baseline levels of 263 +/- 22 ng/ml after 1 h of rest.
      This highly significant effect of exercise on circulating ICAM-1 levels (p <
      .005) was mitigated after treatment with the beta-adrenergic antagonists. Soluble
      E-Selectin levels were not significantly affected by exercise. These results
      suggest that dynamic exercise leads to shedding of the cell adhesion molecule
      ICAM-1 via adrenergic mechanisms. We believe that these findings will contribute
      to the understanding of how physical and mental stress modulate lymphocyte
      migration and adhesion.

PMID- 9512821
TI  - Influencing prescribing patterns.

PMID- 9512822
TI  - Problems of providing limited obstetrical services to small, isolated, rural
      populations.

PMID- 9512823
TI  - Open debate on prescription renewal.

PMID- 9512825
TI  - Practising medicine south of the border.

PMID- 9512824
TI  - And the debate continues.

PMID- 9512827
TI  - Ophthaproblem. Hyphema.

PMID- 9512826
TI  - Breast cancer during pregnancy. Approach to rational management.
AB  - QUESTION: A 35-year-old woman attending my clinic in the 20th week of pregnancy
      had a lump in her breast. Open biopsy revealed ductal carcinoma. Radical
      mastectomy with axillary lymph node biopsy showed three out of 10 nodes positive.
      What are the short- and long-term implications of chemotherapy during pregnancy?
      ANSWER: Patients with breast cancer during pregnancy should be treated using the
      same criteria as their nonpregnant counterparts, with the modifications required
      by pregnancy. The benefits of the diagnostic workup and use of chemotherapy,
      radiotherapy, and surgery have to be weighed carefully against their risk to the
      unborn baby.

PMID- 9512828
TI  - Radiology rounds. Malrotation of the midgut with a nonrotation pattern.

PMID- 9512829
TI  - Dermacase. Melanotic macule of the lip.

PMID- 9512830
TI  - Practice tips. Taping toes. Effective treatment for ingrown toenails.

PMID- 9512831
TI  - Does a structured exercise program benefit elderly people with knee
      osteoarthritis?

PMID- 9512832
TI  - Diagnosing pregnancy. What is the best way?

PMID- 9512833
TI  - Treating hypertension. Are the right drugs given to the right patients?
AB  - OBJECTIVE: To evaluate whether physicians are prescribing antihypertensive drugs
      appropriately and according to the recommendations of the Canadian Hypertension
      Society. DESIGN: Retrospective cohort study. SETTING: Family medicine teaching
      clinic in Montreal. PARTICIPANTS: A cohort of 183 patients followed between 1993
      and 1995. Of 350 patients registered at the clinic, 167 were excluded because
      diagnosis of hypertension was not supported by chart review, their charts
      contained insufficient information, they were pregnant or younger than 18 years,
      or they had secondary hypertension and complex medical conditions. MAIN OUTCOME
      MEASURES: The dependent variable was the antihypertensive medication. Independent
      variables were age and sex of patients, duration of hypertension, total number of
      visits and number of visits for hypertension, number of physicians consulted at
      the clinic, associated medical conditions, diagnosis of target organ damage,
      blood pressure readings, and associated medications. RESULTS: Diuretics were
      prescribed most frequently (45.9%). Angiotensin-converting enzyme (ACE)
      inhibitors ranked second (28.4%), followed by calcium channel blockers (26.2%)
      and beta-blockers (18.0%). Age, sex, duration of hypertension, and blood pressure
      readings were not associated with medications. Prescription of beta-blockers was
      strongly associated with previous myocardial infarction, but not with diagnosis
      of angina pectoris. Patients with contraindications to beta-blockers were less
      likely to receive them and more likely to receive calcium channel blockers. Only
      32% of diabetic patients received ACE inhibitors. CONCLUSION: Results suggest
      that some prescriptions for antihypertensive medications are inappropriate, but
      that physicians are following some of the Canadian Hypertension Society's
      recommendations. A better understanding of physicians' prescribing behaviours
      could help target continuing education interventions to improve prescribing for
      hypertension.

PMID- 9512834
TI  - [Treatment patterns of hypertension in 1996. Data from the Quebec Family
      Practice, University of Sherbrooke registry].
AB  - OBJECTIVE: To describe the treatment of hypertension, alone or in combination
      with associated conditions, by a group of general practitioners in the FAMUS
      network and to compare these treatment patterns to the recommendations of the
      Canadian Hypertension Society Consensus. DESIGN: Descriptive study based on data
      collected by 233 physicians in the FAMUS provincial register on hypertensive
      patients treated in 1996. PARTICIPANTS: Developed between 1992 and 1996, the
      register contains 52,505 patients, 9,094 of whom have high blood pressure. These
      patients consulted their general practitioners for a complete examination. The
      data concern the risk factors for cardiovascular disease and include the list of
      medications prescribed. MAIN OUTCOME MEASURES: Evaluation of the proportions in
      which various classes of medications were prescribed, and the most common
      combinations in relation to the presence or absence of associated conditions.
      RESULTS: Of the 4,049 hypertensive patients seen in 1996, 50.2% were treated with
      one medication; 32.9% were treated with more than one medication; and 16.9%
      received no antihypertensive medication. The most frequently prescribed
      medications were calcium channel blockers (26.1%), followed by diuretics (25.3%),
      angiotensin-converting enzyme inhibitors (24.3%), and beta-blockers (20.0%).
      Other agents made up the remaining 4.3% of prescriptions. The proportions were
      similar for patients without complications who received one medication.
      CONCLUSIONS: Results of this study suggest that the new molecules are widely used
      and that treatment patterns differ from the recommendations of the Canadian
      Hypertension Society Consensus, particularly in the absence of associated
      conditions.

PMID- 9512836
TI  - Alendronate for osteoporosis. Safe and efficacious nonhormonal therapy.
AB  - OBJECTIVE: To review the evidence concerning alendronate (Fosamax) therapy for
      postmenopausal osteoporosis. QUALITY OF EVIDENCE: The efficacy of alendronate for
      postmenopausal women with osteoporosis was primarily demonstrated by two primary
      phase III clinical trials, three other 2-year trials, and one 3-year trial. All
      six trials were randomized double-blind placebo-controlled trials; 3854
      postmenopausal women were studied. The Fracture Intervention Trial consisted of
      2027 women with postmenopausal osteoporosis and provides the most evidence that 3
      years of treatment with alendronate reduces all clinically relevant fractures,
      including hip fractures. MAIN FINDINGS: In postmenopausal women, alendronate has
      been shown to increase bone mineral density significantly at the lumbar spine,
      femoral neck, and trochanter and in the total body, regardless of baseline bone
      mineral density, age, bone turnover, or the presence of previous fractures. In
      addition, alendronate has been shown to reduce risk of new vertebral and hip
      fractures by about 50% and of all clinical fractures by about 30%. Continuous
      daily dosing with alendronate (10 mg) was found to be well tolerated. In
      addition, alendronate was shown to have no adverse effects on bone mineralization
      or microstructure. CONCLUSION: This evidence shows alendronate to be safe and
      effective; it should be considered the nonhormonal therapy of choice for treating
      osteoporosis in postmenopausal women at risk for hip and vertebral fractures.

PMID- 9512835
TI  - Bacteremia in nursing home patients. Prevalence among patients presenting to an
      emergency department.
AB  - OBJECTIVE: To measure the prevalence of bacteremia and any correlation between
      signs and symptoms, risk factors, and laboratory data in elderly patients.
      DESIGN: Prospective analysis. All patients were contacted by the study nurse at
      48 hours and 7 days after study entry. SETTING: Adult tertiary care hospital with
      an emergency department managing 48,000 visits yearly in a metropolitan area of
      250,000. PARTICIPANTS: Members of the study population referred to the emergency
      department for medical or surgical problems. Of 113 nursing home patients, blood
      culture results were available for 111. MAIN OUTCOME MEASURES: Blood cultures
      were obtained by standard protocol. Demographic and medical information was
      collected from the medical record. Three groups of patients were compared with
      respect to symptoms, risk factors, laboratory data, and outcome. RESULTS: Group 1
      (n = 86) had two sets of negative blood cultures. Group 2 (n = 10) had true
      positive cultures. Group 3 (n = 15) had false-positive cultures of Staphylococcus
      epidermidis. The prevalence of bacteremia was 9.8% in the study population. No
      risk factors were predictive of bacteremia. Great variation in signs and symptoms
      were noted in all three groups, none correlating with bacteremia. Although seven
      of the 10 patients with positive cultures were febrile, this association did not
      reach statistical significance. All groups had high admission (> 50%) and
      mortality (20% to 37%) rates. CONCLUSIONS: The prevalence of bacteremia in the
      nursing home population presenting to the emergency department was 9.8%. The
      symptoms and signs of bacteremia in this population were variable and
      nonspecific. The high rate of false-positive cultures in this setting is of
      concern.

PMID- 9512838
TI  - How current is your travel health information?

PMID- 9512837
TI  - Screening for childhood strabismus by primary care physicians.
AB  - OBJECTIVE: To review the clinical classification of strabismus, to describe the
      timing and method of strabismus screening examinations, and to discuss the
      principles of treatment. QUALITY OF EVIDENCE: Current literature (1983 to 1995)
      was searched via MEDLINE using the MeSH headings strabismus, ocular motility
      disorders, and amblyopia. Articles were selected based on their date of
      publication, clinical relevance, and availability. Preference was given to more
      recent articles, articles with large numbers of subjects, and well-designed
      cohort studies. Official recommendations from academic groups were analyzed.
      Descriptions of clinical tests and their illustrations are based on classic
      texts. MAIN FINDINGS: Primary care physicians should screen all low-risk
      children. High-risk children (low birth weight, family history of strabismus,
      congenital ocular abnormality, or systemic conditions with vision-threatening
      ocular manifestations) should be referred to an ophthalmologist for screening.
      Screening should be performed in the neonatal period, at 6 months, and at 3 years
      (Grade A recommendation), as well as at 5 to 6 years (Grade B recommendation).
      Screening examination includes inspection, examining visual acuity, determining
      pupillary reactions, checking ocular alignment, testing eye movements, and
      ophthalmoscopy. CONCLUSIONS: Primary care physicians are essential to early
      detection of strabismus and amblyopia. Early detection can help minimize visual
      dysfunction, allow for normal development of binocular vision and depth
      perception, and prevent psychosocial dysfunction.

PMID- 9512839
TI  - Medical care of the rich and famous.

PMID- 9512840
TI  - Our strength for tomorrow: valuing our children. Part 7: Aboriginal children.
      Report of the CFPC's Task Force on Child Health.

PMID- 9512841
TI  - Epidural ketamine for postoperative analgesia.

PMID- 9512842
TI  - Epidural ketamine reduces post-operative epidural PCA consumption of
      fentanyl/bupivacaine.
AB  - PURPOSE: To study the analgesic effect of epidural ketamine on postoperative pain
      and epidural PCA consumption after total abdominal hysterectomy. METHODS: Sixty
      one ASA I-II patients, 34-60 yr were randomly assigned into three groups.
      Epidural catheters were inserted before induction of anaesthesia. Patients in
      group I and II received 30 mg ketamine epidurally before induction of anaesthesia
      or 20 min after skin incision: group III received placebo. Postoperatively, on
      first analgesia request, sedation score, Visual Analogue Scale (VAS), Prince
      Henry Score (PHS) and Bromage motor weakness score were taken and followed by an
      epidural bolus of 9 ml bupivacaine 0.25% + 50 micrograms fentanyl. Analgesia was
      maintained by PCA with a mixture of bupivacaine 0.1% + fentanyl 0.001%
      epidurally. Measurements were repeated at 1, 2, 4, 8, 12 and 24 hr. RESULTS:
      First analgesia request was 17 +/- 6.8 min in the control group compared with
      31.4 +/- 23.8 and 44 +/- 23.1 min for groups I and II respectively. The
      differences between group III and group I (P < 0.05) and between group III and
      group II (P < 0.01) were statistically significant. Twenty four hour PCA
      consumption was 101.2 +/- 47.2, 87 +/- 27 and 162 +/- 38 ml for groups I, II and
      III respectively. The differences between group III and group I and that between
      group III and group II were statistically significant (P < 0.001). CONCLUSION:
      Epidural ketamine 30 mg reduces post hysterectomy pain as evidenced by
      prolongation of time to first analgesia request and reduction in postoperative
      epidural PCA consumption. This effect is manifest whether ketamine is given
      before induction or 20 min after skin incision.

PMID- 9512843
TI  - North American survey of the management of dural puncture occurring during labour
      epidural analgesia.
AB  - PURPOSE: To document the range and the most common strategies for the management
      of the parturient with inadvertent dural puncture (DP) during labour epidural
      analgesia. METHODS: A confidential survey form was mailed to 46 academic units in
      Canada and USA. The responses were compiled into Canadian, US and joint North
      American databases. RESULTS: Thirty-six centres (78%) responded, representing
      137,250 annual deliveries. The reported incidence of DP was 0.04-6%. The most
      common initial response to DP was resiting the catheter at another level. Most
      centres made little change in routine practice regarding epidural top-ups and
      infusion rates after DP. Unrestricted mobilisation was advocated by 86% of
      centres following delivery; enhanced oral hydration was encouraged by 61%.
      Prophylactic epidural blood patch (PEBP) was recommended by 37% of centres, with
      twice as many US as Canadian centres doing so. In the presence of PDPH, EBP was
      offered most commonly at or within 24 hr of diagnosis. Complications were common
      after EBP: 86% of centres reported patch failures; 44% reported persistent
      headache after > or = 2 EBP. Despite this, centres remained optimistic about EBP
      success, quoting cure rates > 90% in 58% of centres. CONCLUSION: There is little
      difference between the practices reported by Canadian or US centres. The
      expressed optimism regarding the efficacy of EBP is not supported by the evidence
      available and may be unwarranted. More research is needed to define the issue
      better.

PMID- 9512844
TI  - 40 Hz auditory steady-state response and EEG spectral edge frequency during
      sufentanil anaesthesia.
AB  - PURPOSE: The auditory steady-state evoked response (ASSR) is an evoked potential
      which provides a sensitive measure of the effects of general anaesthetics on the
      brain. We used pharmacokinetic-pharmacodynamic (PK-PD) modelling to compare the
      effects of sufentanil on the amplitude of the ASSR with its effect on spectral
      edge frequency (SEF) of the electroencephalogram. METHODS: Nine patients
      scheduled for elective cardiac surgery participated. Midazolam (70 micrograms.kg
      1 i.m.) was given 60 min before entering the operating room. Anaesthesia was
      induced with 5 micrograms.kg-1 sufentanil at a rate of 0.83 microgram.kg-1.min-1.
      The ASSR, SEF and plasma sufentanil concentrations were measured for 30 min after
      induction of anaesthesia before surgery. The half-life between the central and
      effect site compartments (t1/2Keo), the 50% inhibitory concentration (IC50) and
      the slope factor (gamma) were computed. RESULTS: The amplitude of the ASSR
      increased during the first three minutes of infusion of sufentanil by up to 40%.
      This was followed by a rapid decrease between the fourth and fifth minutes to 16%
      of baseline. The SEF decreased progressively during the first five minutes of
      infusion to 18% of baseline. Both measures subsequently showed modest recovery.
      The parameters gamma, IC50 and t1/2Keo for ASSR were (mean +/- SD) 6.0 +/- 3.7,
      2.1 +/- 1.2 ng.ml-1 and 7.3 +/- 2.4 min. For SEF the values were 5.9 +/- 5.2, 1.4
      +/- 0.7 ng.ml-1 (P < 0.05 compared with ASSR) and 6.8 +/- 2.4 min. CONCLUSION:
      The sensitivity of ASSR to sufentanil is less than that of the SEF.

PMID- 9512845
TI  - Minimum effective anaesthetic concentration of hyperbaric lidocaine for spinal
      anaesthesia.
AB  - PURPOSE: Minimum effective anaesthetic concentration (MEAC) of lidocaine for
      spinal anaesthesia, defined as the concentration at which a spinal anaesthetic
      agent produces surgical anaesthesia within 20 min of administration in 50% of
      patients, was determined in a randomised, double-blind study in young patients
      undergoing knee and ankle surgery. METHODS: Using the combined spinal-epidural
      technique, 48 or 72 mg hyperbaric lidocaine containing dextrose 7.5% was
      administered intrathecally to 43 patients at concentrations ranging from 0.2
      0.9%. The choice of lidocaine concentration was determined by Dixon's up-and-down
      method. Complete anaesthesia was defined as: (1) pinprick anaesthesia at or
      higher than T12, (2) anaesthesia to transcutaneous tetanic electric stimulation
      (50 Hz at 60 mA for five seconds) in the knees and (3) complete leg paralysis;
      all occurring in both lower extremities within 20 min. Epidural anaesthesia was
      initiated if anaesthesia was incomplete. RESULTS: In the 48 mg group, MEAC was
      0.54% (95% CI-0.21-0.87). Anaesthetic effect was variable with mean duration of
      anaesthesia of 29 min (range: 20-50 min) and maximum pinprick sensory level
      ranging from T2-T10. In the 72 mg group, successful anaesthesia was achieved
      consistently at a concentration of 0.3%, i.e., MEAC was < 0.3%. Mean duration of
      complete anaesthesia was 46 min (range: 30-60 min) with maximum sensory level
      from T3-T8. DISCUSSION: Spinal anaesthesia can be accomplished with very dilute
      lidocaine solutions (< 0.9%). The value of MEAC is dose-dependent, i.e., complete
      anaesthesia can be accomplished with lower concentrations by increasing the dose
      of spinal anaesthetic administered.

PMID- 9512846
TI  - Cardiac arrest in the OR: how are our ACLS skills?
AB  - PURPOSE: While advanced cardiac life support (ACLS) training is widely available,
      it is not mandatory for all anaesthetists. We hypothesised that adherence to ACLS
      guidelines during resuscitation of ventricular fibrillation (VFib) as assessed in
      a simulator environment would be poor by anaesthetists not trained in ACLS
      compared with those who had received training. METHODS: With approval by the
      ethics review board, 89 subjects participated in the study. The simulation system
      consisted of a computer controlled mannequin with lifelike qualities set in a
      mock operating room. Each subject was given a test scenario that contained
      several standard anaesthetic problems. A VFib cardiac arrest occurred after
      approximately one hour into the simulation. A perfect score (score = A) defined
      complete compliance with the ACLS guidelines, whereas minor deviations (score =
      B) included changes in energy levels, drug doses or treatment order. The failure
      to discontinue the anaesthetic, defibrillate or administer epinephrine were
      considered major deviations (score = C). RESULTS: Eight subjects followed the
      ACLS guidelines (9%, score = A), while 27 subjects showed minor (30%, score = B)
      and 54 subjects major deviations (61%, score = C). Sixty-two of the 89
      participants (70%) had taken the ACLS course and achieved higher scores than did
      anaesthetists without such training (P < 0.05). Forty-two participants (47%) did
      not discontinue the anaesthetic, 10 (11%) never gave epinephrine and 5 (6%) never
      used the defibrillator. CONCLUSION: Adherence to ACLS guidelines was poor. A
      greater proportion of subjects without previous ACLS training had deviations from
      protocol than did subjects who had received training. We need to consider ways to
      ensure that anaesthetists obtain and retain resuscitation skills according to
      ACLS guidelines.

PMID- 9512847
TI  - Cardiac output during liver transplantation.
AB  - PURPOSE: Measurement of cardiac output is an essential part of anaesthetic
      practice in patients undergoing major operative procedures. A thermodilution
      technique, using a pulmonary artery catheter is currently accepted as the gold
      standard in clinical practice. However its use is associated with several
      limitations. METHOD: In this prospective randomised controlled study measurement
      of cardiac output, an oesophageal Doppler monitor (ODM) was compared with the
      thermodilution technique in 18 patients undergoing orthotopic liver
      transplantation. Measurements were taken during the three phases of liver
      transplantation, i) dissection phase (three measurements), ii) anhepatic phase
      (four) and iii) reperfusion phase (six). RESULTS: There were no differences
      observed between the two measurements at any of the times studied and a strong
      correlation was observed (r = 0.714; P < 0.00001). However, when the data was
      analysed using Bland and Altman analysis, while the mean difference was small
      (0.07 l.min-1) it was > 2 l.min-1 in one third of measurements recorded i.e., the
      bias was near zero but the precision was large. No consistent differences were
      seen using the two methods in individual patients. CONCLUSION: The use of the ODM
      results in cardiac output measurements which are considerably different from
      those obtained using thermodilution and its use cannot be recommended in patients
      undergoing orthotopic liver transplantation.

PMID- 9512848
TI  - Haemodynamic effects of rocuronium bromide in adult cardiac surgical patients.
AB  - PURPOSE: To measure the haemodynamic effects of rocuronium in adults undergoing
      cardiac surgery with cardiopulmonary bypass (CPB). METHODS: Twenty patients
      undergoing elective cardiac surgical procedures with moderate hypothermic
      nonpulsatile bypass participated in this prospective, observational study. After
      anaesthetic induction, recovery from succinylcholine, and achievement of baseline
      haemodynamic stability, patients received 0.6 mg.kg-1 rocuronium as an initial
      rapid intravenous bolus. Maintenance dosing of 0.2 mg.kg-1 was continued for the
      remainder of the procedure. Haemodynamic measurements (heart rate, systemic
      arterial systolic, diastolic, and mean arterial pressure, pulmonary arterial
      systolic, diastolic, and mean pressure, pulmonary capillary wedge pressure,
      central venous pressure, and thermodilution cardiac output measurements) were
      obtained for the first five minutes after rocuronium administration, and subjects
      were observed for histamine-related symptoms. RESULTS: Central venous pressure
      decreased from baseline at two and five minutes after the rocuronium bolus, and
      mean pulmonary artery pressure decreased at five minutes. No changes were
      observed in heart rate, mean systemic arterial pressure, pulmonary capillary
      wedge pressure, cardiac index, stroke volume, systemic vascular resistance, or
      pulmonary vascular resistance, nor did any patient manifest any other histamine
      related symptoms. CONCLUSION: The haemodynamic profile for a 0.6 mg.kg-1 bolus of
      rocuronium is acceptable for patients with cardiovascular disease.

PMID- 9512849
TI  - Predictors of hospital mortality and mechanical ventilation in patients with
      cervical spinal cord injury.
AB  - PURPOSE: The objective of this study was to identify predictors of death and
      mechanical ventilation in patients with traumatic cervical spinal cord injury.
      METHODS: From 1981 to 1994, 72 patients with traumatic cervical spinal cord
      injury resulting in neurological deficits were identified in this retrospective
      study. For each patient, neurological and associated injuries, physiological
      variables, complications, hospital mortality and the need for mechanical
      ventilation were recorded. Univariate and multivariate logistic regression
      analyses were done to identify predictors of mortality and the need for
      mechanical ventilation. RESULTS: Fifteen patients (21%) died in the first three
      months after injury. Univariate analyses identified age, heart disease,
      neurological level at C4 and above, GCS < or = 13, forced vital capacity and
      cough, to be associated with mortality. Multivariate logistic regression
      identified age (P = 0.01), neurological level (P = 0.03) and GCS (P = 0.05) as
      independent predictors of mortality. In 41 patients (57%), the lungs were
      mechanically ventilated. Univariate analyses identified. The following predictors
      of the need for mechanical ventilation: neurological level at C5 and above,
      complete cord lesions, copious sputum, pneumonia and lung collapse. Multivariate
      logistic regression identified copious sputum (P = 0.01) and pneumonia (P = 0.01)
      as independent predictors of the need for mechanical ventilation. CONCLUSION:
      Age, neurological level and GCS are independent predictors of mortality in
      patients with traumatic cervical spinal cord injury. Copious sputum and pneumonia
      are independent predictors of the need for mechanical ventilation.

PMID- 9512850
TI  - Awake removal of the laryngeal mask airway is safe in paediatric patients.
AB  - PURPOSE: It has been suggested that it is safer to remove the Laryngeal Mask
      Airway (LMA) in paediatric patients when they are deeply anaesthetised than when
      they are awake. However, the evidence regarding this recommendation is
      contradictory. The purpose of the study was to compare the incidence of
      complications (laryngeal spasm, bronchospasm, coughing, retching, excessive
      salivation and oxygen desaturation) associated with removal of the LMA in
      children. METHODS: In a randomised study, we studied 165 ASA physical status I
      infants and children of both sexes, aged 2 mo to 13 yr. All patients were
      undergoing elective lower limb or perineal surgery. They were randomly assigned
      to two groups: in 83 the laryngeal mask was removed when recovery of airway
      reflexes had been demonstrated and the patients had opened their eyes or mouth in
      the recovery area. In the other 82 patients it was removed with the patient
      deeply anaesthetised. RESULTS: Two (2.4%) patients developed laryngeal spasm in
      the anaesthetised group, one patient (1.2%) desaturated and another vomited
      (1.2%) in the awake group. CONCLUSION: There was no difference in the incidence
      of airway complications whether the LMA was removed in the anaesthetised or the
      awake child.

PMID- 9512851
TI  - Prevention of PONV with granisetron, droperidol or metoclopramide in patients
      with postoperative emesis.
AB  - PURPOSE: A high incidence of postoperative nausea and vomiting (PONV) has been
      noted in patients with a history of postoperative emesis. This study was
      undertaken to compare the efficacy of granisetron, droperidol and metoclopramide,
      in the prevention of PONV in such patients undergoing general anaesthesia for
      major gynaecological surgery. METHODS: In a randomised, double-blind study, 90
      female patients received 2.5 mg granisetron, 1.25 mg droperidol or 10 mg
      metoclopramide (n = 30 of each) i.v. immediately before induction of anaesthesia.
      The same standard general anaesthetic technique, which consisted of isoflurane in
      nitrous oxide and oxygen, was used. Nausea, vomiting and safety assessments were
      performed continuously during the first 24 hr after anaesthesia. RESULTS: The
      incidence of PONV was 20% with granisetron, 57% with droperidol and 60% with
      metoclopramide (P < 0.05; overall Fisher's exact probability test). No clinically
      adverse events were observed in any group. CONCLUSION: Granisetron is more
      effective than droperidol or metoclopramide in preventing PONV in female patients
      with a history of postoperative emesis.

PMID- 9512852
TI  - Anaesthetic management of caesarean section in a patient with myelodysplastic
      syndrome.
AB  - PURPOSE: This case report describes the anaesthetic management for Caesarean
      section in a patient with myelodysplastic syndrome. CLINICAL FEATURES: A woman
      with myelodysplastic syndrome underwent Caesarean section on two occasions. The
      first Caesarean section was performed at age 20 yr using general anaesthesia with
      nitrous oxide-oxygen and fentanyl. In her second pregnancy at 25 yr, there was
      severe pancytopenia at 28-wk gestation with a leukocyte count 3.6 x 10(9).L-1,
      erythrocyte count 1.2 x 10(12).L-1, haemoglobin 50 g.L-1, haematocrit 14.7% and
      platelet count 51 x 10(9).L-1. Following leukocyte poor red cells and platelet
      transfusion, general anaesthesia was maintained with nitrous oxide-oxygen
      sevoflurane and fentanyl. Both operations were uneventful and healthy infants
      were delivered. CONCLUSION: It is important to have a team approach
      (anaesthetist, obstetrician and haematologist) for the perianaesthetic management
      of patients with myelodysplastic syndrome. An exact assessment of the
      haematological condition, the need for prophylactic treatment and anaesthetic
      management should be determined for each individual patient.

PMID- 9512853
TI  - Transcutaneous PCO2 monitoring during laparoscopic cholecystectomy in pregnancy.
AB  - PURPOSE: Respiratory acidosis during carbon dioxide (CO2) insufflation has been
      suggested as a cause of spontaneous abortion and preterm labour following
      laparoscopic cholecystectomy during pregnancy. Capnography may not be adequate as
      a guide to adjust pulmonary ventilation during laparoscopic surgery and hence
      arterial carbon dioxide (PaCO2) monitoring has been recommended. We report the
      feasibility and benefits of transcutaneous carbon dioxide monitoring (PtcCO2) as
      an approach to optimise ventilation during laparoscopic surgery in pregnancy.
      METHOD: A healthy parturient received general anaesthesia for laparoscopic
      cholecystectomy. Pulmonary ventilation was adjusted to maintain end-tidal carbon
      dioxide (conventional PETCO2) at 32 mmHg during CO2 insufflation. A PtcCO2
      monitor was used to trend PaCO2 throughout the procedure. Mechanical ventilation
      was interrupted every five minutes to obtain an end-tidal PCO2 value at large
      tidal volume (squeeze PETCO2). RESULTS: The PtcCO2 increased from 39 mmHg before
      induction to 45 mmHg after CO2 insufflation. This corresponds to an estimated
      maximum PaCO2 of 39-40 mmHg during insufflation. The PtcCO2 gradually returned to
      pre-induction baseline values one hour after the termination of CO2 insufflation.
      Squeeze PETCO2 values approximated PtcCO2 more closely than did conventional
      PETCO2 values (P < 0.01). CONCLUSION: Continuous PtcCO2 measurements as well as
      squeeze PETCO2 may be of clinical value in trending and preventing hypercarbia
      during laparoscopic surgery.

PMID- 9512854
TI  - A surgically placed epidural catheter in a patient with spinal trauma.
AB  - PURPOSE: To report the successful perioperative anaesthetic and analgesic
      management of a spinal trauma patient with a surgically placed epidural catheter.
      CLINICAL FEATURES: A 15-yr-old adolescent woman sustained an unstable spinal
      column injury with an incomplete neurological deficit following a high speed
      motor vehicle accident. She was scheduled for spinal decompression and
      stabilisation through a left thoracoabdominal approach. Balanced general
      anaesthesia was undertaken. Prior to closure, a multi-orifice epidural catheter
      was surgically placed under direct vision 5 cm into the anterior epidural space.
      The catheter was then tunnelled out through the psoas muscle and secured in
      place. Combined epidural-general anaesthesia was then initiated for the duration
      of the case using 5 ml bupivacaine 0.25% after an initial test dose of 3 ml
      lidocaine 1.5% with epinephrine. An infusion of bupivacaine 0.10% and fentanyl 5
      micrograms.ml-1 at 8 ml.hr-1 using patient controlled epidural analgesia (PCEA)
      provided excellent postoperative pain control for four days. She had an
      uncomplicated postoperative course. CONCLUSION: A surgically placed epidural
      catheter provided excellent, safe, perioperative anaesthesia and analgesia in
      this patient with unstable spinal trauma.

PMID- 9512855
TI  - Long-term epidural ketamine, morphine and bupivacaine attenuate reflex
      sympathetic dystrophy neuralgia.
AB  - PURPOSE: There is considerable evidence that NMDA receptor antagonists can
      abolish nociceptor hypersensitivity in animals. In the present case report, two
      patients with reflex sympathetic dystrophy were treated with ketamine, a NMDA
      antagonist, morphine and bupivacaine. CLINICAL FEATURES: Two patients were
      referred suffering from severe pain, allodynia, hyperaesthesia, swelling and
      disability over their right lower legs, diagnosed as reflex sympathetic
      dystrophy. They had received conventional treatments with non-steroid anti
      inflammatory drugs (NSAIDs), steroids, anticonvulsant, antidepressant, epidural
      lidocaine sympathetectomy and rehabilitation which failed to provide satisfactory
      pain relief. We administered subanalgesic doses of ketamine (7.5 mg), morphine
      (0.75 mg) and 6 ml bupivacaine 0.1% via a lumbar epidural catheter three times
      per day. After several courses of treatment over three and six months,
      satisfactory pain relief was achieved in each patient. Both are now able to walk
      with slight weight bearing with the assistance of crutch. The treatment is
      continuing with further improvement of symptoms and signs. CONCLUSION: Epidural
      coadministration of low doses of morphine, ketamine and bupivacaine provided
      effective pain relief in two patients. This suggests synergy from this
      combination that provides an alternative treatment for reflex sympathetic
      dystrophy.

PMID- 9512856
TI  - Cardiovascular responses to tracheal extubation or LMA removal in children.
AB  - PURPOSE: This study was designed to investigate the cardiovascular effects
      related to tracheal extubation or laryngeal mask airway (LMA) removal in
      children. METHODS: Sixty children, ASA physical status 1, 4-10 yr of age,
      undergoing minor elective surgery (inguinal hernia and phimosis) were allocated
      randomly to have their surgery performed with endotracheal intubation (Group ET,
      n = 30) or LMA (Group LMA, n = 30) and were studied for cardiovascular responses
      related to extubation or LMA removal. Changes in heart rate (HR), systolic blood
      pressure (SBP) and diastolic blood pressure (DBP) were measured before and 1, 2,
      3, 5, and 10 min after tracheal extubation or LMA removal when the patients were
      awake. RESULTS: The maximal changes in HR, SBP and DBP were less in Group LMA
      than in Group ET during the observation period (HR; 12 vs 26, SBP; 14 vs 28, DBP;
      9 vs 13, median, P < 0.05). CONCLUSION: Laryngeal mask airway removal elicited
      less haemodynamic change than tracheal extubation in paediatric patients.

PMID- 9512857
TI  - Artefactual episodic hypoxaemia during postoperative respiratory monitoring.
AB  - PURPOSE: To determine the reliability of continuous pulse oximetry in the
      detection of episodic hypoxaemia in total hip joint replacement patients.
      Episodic hypoxaemia has been described in postoperative patients and is
      associated with analgesic technique. This study compared the incidence of
      hypoxaemic episodes identified solely by pulse oximetry and then subsequently
      where additional monitoring, as indicated for sleep-related breathing disorders,
      was also utilised. METHODS: Eight patients were studied on the night before and
      for three nights after surgery. Pulse oximetry, ECG, chest impedance, nasal and
      oral airflow and transcutaneous CO2 were recorded. Sudden episodic hypoxaemia was
      defined as a decrease in oxygen saturation of > or = 5% within two minutes, for >
      five seconds and with a nadir of < 90%. Artefacts were identified by noise
      signals on the ECG and impedance recordings and by a motion annotation wave
      superimposed on the oximetry trace. RESULTS: Using these criteria 172 (79%) of
      219 desaturation events were classified as artefactual. The median duration of
      genuine events was greater (P < 0.001 Mann Whitney U test) than artefactual
      events; 21 sec (range, 6-443) vs 11 sec (5-63). Genuine desaturations reached a
      median nadir of SpO2 87% (range 83-89%) compared with 81% (61-88%) for the
      artefactual. These differences were statistically significant (P < 0.001).
      CONCLUSION: Previous studies utilising unobserved pulse oximetry data alone may
      have overestimated the incidence of episodic hypoxaemic events in postoperative
      patients.

PMID- 9512858
TI  - Accuracy of transcutaneous carbon dioxide measurement.

PMID- 9512859
TI  - Misuse of infusion pump during propofol anaesthesia.

PMID- 9512860
TI  - Awake fibre-optic intubation.

PMID- 9512861
TI  - Use and misuse of syringes.

PMID- 9512862
TI  - Transfusion practices among Mexican anaesthesiologists.

PMID- 9512863
TI  - An anaphylactoid-like reaction following infusion of salvaged unwashed drain
      blood.

PMID- 9512864
TI  - A simple anaesthetic delivery system for magnetic resonance imaging.

PMID- 9512865
TI  - Congestive heart failure and genomic medicine: a look into the 21st century.
AB  - Congestive heart failure (CHF) has emerged as one of the leading cardiovascular
      disorders in developed countries, as indicated by the prevalence of the disease;
      the incidence of hospitalization, morbidity, and mortality; and its global
      economic burden. Furthermore, it is expected that heart failure and other
      cardiovascular disorders will become the major disease burdens in developing
      countries by the year 2020. It is well established that pharmacological therapy
      of CHF, although still not optimum, improves patient quality of life and reduces
      morbidity and mortality. However, CHF remains a relentlessly progressive disease.
      In this brief review an attempt is made to explore the contemporary, state-of-the
      art pharmacological approach to the treatment of heart failure, the unmet medical
      need that still remains, and the potential impact of genomic medicine on the
      treatment of heart failure in the 21st century.

PMID- 9512866
TI  - New developments in cardiovascular drugs: vitamin E and antioxidants--an informal
      and personal viewpoint.

PMID- 9512867
TI  - T-type Ca2+ channels and pharmacological blockade: potential pathophysiological
      relevance.
AB  - Low-voltage-activated T-type Ca2+ channels are present in most excitable tissues
      including the heart (mainly pacemaker cells), smooth muscle, central and
      peripheral nervous systems, and endocrine tissues, but also in non-excitable
      cells, such as osteoblasts, fibroblasts, glial cells, etc. Although they comprise
      a slightly heterogeneous population, these channels share many defining
      characteristics: small conductance (< 10 pS), similar Ca2+ and Ba2+
      permeabilities, slow deactivation, and a voltage-dependent inactivation rate. In
      addition, activation at low voltages, rapid inactivation, and blockade by Ni2+
      are classical properties of T-type Ca2+ channels, which are less specific. T-type
      Ca2+ channels are weakly blocked by standard Ca2+ antagonists. Pharmacological
      blockers are scarce and often lack specificity and/or potency. The physiological
      modulation of T-type Ca2+ currents is complex: they are enhanced by endothelin-1,
      angiotensin II (AT1-receptor), ATP, and isoproterenol (cAMP-independent), but are
      reduced by angiotensin II (AT2-receptor), somatostatin and atrial natriuretic
      peptide. Norepinephrine enhances these currents in some cells but decreases them
      in others. T-type Ca2+ currents have many known or suggested physiological and
      pathophysiological roles in growth (protein synthesis, cell differentiation, and
      proliferation), neuronal firing regulation, some aspects of genetic hypertension,
      cardiac hypertrophy, cardiac fibrosis, cardiac rhythm (normal and abnormal), and
      atherosclerosis. Mibefradil is a new Ca2+ antagonist that is effective in
      hypertension and angina pectoris. Its favorable pharmacological profile and
      limited side effects appear to be related to selective block of T-type Ca2+
      channels: mibefradil reduces vascular resistance and heart rate without negative
      inotropy or neurohormonal stimulation, and it also has significant
      antiproliferative actions.

PMID- 9512868
TI  - Verapamil normalizes the response of left ventricular early diastolic filling to
      cold pressor test in asymptomatic and mildly symptomatic patients with
      hypertrophic cardiomyopathy.
AB  - The aim of the study was to assess the left ventricular (LV) diastolic filling
      response to the cold pressor test in asymptomatic or mildly symptomatic patients
      with nonobstructive hypertrophic cardiomyopathy (HC) before and after verapamil
      therapy. The cold pressor test-induced alterations in LV filling pattern were
      additionally compared between HC patients and healthy control subjects. The cold
      pressor test, producing alpha- and beta-adrenergic stimulation, differentiates
      paradoxical coronary vasoconstriction due to endothelial dysfunction from the
      normal endothelium-dependent vasodilation. Such opposite coronary vasomotion at
      cold pressor test may be reflected by different responses of LV diastolic filling
      to the cold pressor test. Doppler echocardiography was performed in 10
      asymptomatic or mildly symptomatic patients with nonobstructive HC as well as in
      10 age- and sex-matched healthy subjects before and immediately after the cold
      pressor test. In HC patients before verapamil therapy, the cold pressor test
      induced a significant decrease in LV early filling parameters, contrary to
      healthy subjects, in whom the cold pressor test improved early filling [changes
      in early diastolic LV velocity -6.2 +/- 7.3 (-11.4 to -0.98) vs. 7.5 +/- 8.9
      (1.13-13.86) cm/s, P = 0.0014, and changes in its acceleration rate -136 +/- 119
      (-221 to -51) vs. 252 +/- 181 (122-381) cm/s2, P = 0.0001, respectively].
      Verapamil therapy restored the normal pattern of the LV early filling response to
      the cold pressor test [changes in early diastolic LV velocity -6.2 +/- 7.3 (-11.4
      to -0.98) vs. 5.3 +/- 3.4 (2.86 to 7.73) cm/s, P = 0.0003, and changes in its
      acceleration rate -136 +/- 119 (-221 to -51) vs. 328 +/- 185 (196 to 460) cm/s2,
      P = 0.0001, respectively]. Verapamil normalizes the LV early filling response to
      the cold pressor test in asymptomatic or mildly symptomatic patents with HC.

PMID- 9512869
TI  - Effects of monatepil, a novel calcium antagonist with alpha 1-adrenergic blocking
      activity, on the low-density lipoprotein receptor in human skin fibroblasts.
AB  - To investigate the mechanisms of the hypolipidemic effect of monatepil, a new
      class of calcium antagonists with alpha 1-adrenergic blocking activity, we
      examined the effects of the drug on low-density lipoprotein (LDL) receptor
      activity and the level of LDL receptor mRNA present in cultured human skin
      fibroblasts. At concentrations of 2 x 10(-5) M, monatepil increased the binding
      (248 +/- 43%; mean +/- SD), internalization (374 +/- 18%), and degradation (145
      +/- 2%) of 125I-LDL in human skin fibroblasts (n = 3, p < 0.05). Treatment of
      human skin fibroblasts with 2 x 10(-5) M of monatepil for 6 hours resulted in an
      increase in LDL receptor mRNA to 163% of the control level (n = 2), as shown by
      Northern blot analysis. Our results suggest that the hypolipidemic clinical
      effects of monatepil may be due to increased LDL receptor activity.

PMID- 9512870
TI  - Bradycardia induced by mivazerol, a selective alpha 2-adrenoceptor agonist, is
      amplified during mild hypothermia in the pentobarbital-anesthetized rat.
AB  - Mivazerol, 3-[1(H-imidazol-4-yl)methyl]-2-hydroxybenzamide hydrochloride, is a
      selective alpha 2-adrenoceptor agonist designed for the prevention of myocardial
      infarction in perioperative patients. Because unintended hypothermia occurs
      frequently during surgery, we were interested, in this study, to examine the
      relationship between body temperature and the bradycardic response induced by
      mivazerol. Experiments were carried out in pentobarbital-anesthetized and
      artificially ventilated rats. The femoral artery and vein were cannulated for the
      measurement of blood pressure and heart rate, and for intravenous infusion.
      Rectal temperature was maintained at 37.5 +/- 0.3 degrees C for normothermic
      groups or at 35.5 +/- 0.3 degrees C for hypothermic groups. Intravenous infusion
      of vehicle had no significant effect on mean arterial pressure and heart rate
      between the normothermic and hypothermic rats. Mivazerol dose-dependently
      produced a decrease in heart rate in normothermic rats, which became more
      pronounced in mildly hypothermic rats, but did not induce any significant change
      in mean arterial pressure in either thermic condition. These results show that
      the bradycardic effect of mivazerol, an alpha 2-adrenoceptor agonist, is
      amplified during mild hypothermia, a condition that occurs frequently in
      perioperative patients.

PMID- 9512871
TI  - Nicorandil improves ischemic changes in epicardial ECG during short-term coronary
      occlusion by opening ATP-sensitive potassium channels in pigs.
AB  - The aims of this study were to investigate whether nicorandil (NIC), an ATP
      sensitive potassium channel (KATP) opener and nitrate, has antiischemic effects
      during transient ischemia in pigs, and to investigate whether its effects are due
      to its KATP-opening action or nitrate action. Myocardial ischemia was induced by
      ligating the proximal portion of the left anterior descending coronary artery for
      1 minute in anesthetized open-chest pigs, and was measured as the magnitude of ST
      segment elevation on epicardial electrocardiogram (ECG). Epicardial ST-segment
      elevation during coronary occlusion was significantly reduced by pretreatment
      with NIC (3 mg, intracoronary [i.c.]), but not by pretreatment with nitroglycerin
      (NTG, 0.2 mg, i.c.). Pretreatment with glibenclamide (GLB, a KATP blocker, 6 mg,
      i.c.) significantly augmented the ST-segment elevation during coronary occlusion.
      The augmentation of ST-segment elevation by GLB was significantly reduced by
      subsequent administration of NIC, but not by that of NTG (0.2 mg, i.c.). There
      were no significant differences between hemodynamic variables immediately before
      coronary occlusion with and without pretreatment. The intracoronary
      administration of NIC (3 mg) significantly shortened the endocardial monophasic
      action potential durations at 50% (MAPD50) and 90% repolarization (MAPD90) by
      28.3 +/- 6.9% and 17.0 +/- 4.7%, respectively. These results suggest that the
      intracoronary administration of NIC has antiischemic effects during transient
      ischemia via KATP activation in myocardium.

PMID- 9512872
TI  - Different effects of flecainide on atrioventricular conduction properties in the
      adult and immature rabbit heart.
AB  - The influence of flecainide (0.1, 0.5, 1.0, and 2.0 micrograms/mL) on
      atrioventricular (AV) conduction was studied in neonatal and adult perfused
      rabbit hearts using extracellular bipolar surface electrograms and premature
      atrial and ventricular pacing. Flecainide produced a concentration and rate
      related increase in the steady-state nodal conduction (AHmin) and an increase in
      slow AH conduction (AHmax) in both age groups. The drug produced significant
      increases in the refractory periods of the atrium, AV node, His-Purkinje system,
      and ventricular myocardium. The neonatal refractory periods were significantly
      greater at lower or the same drug concentrations than those of the adult. The
      neonatal Wenckebach cycle length was significantly greater with a lower
      concentration of drug (0.5 microgram/mL) than was the adult Wenckebach cycle
      length. The His-Purkinje system steady-state conduction time (HVmin) was
      increased by a lower concentration of drug in the neonate (0.5 microgram/mL) as
      compared with 2.0 micrograms/mL in the adult. These data show that across a wide
      range of AV conduction parameters, the neonatal preparations responded to a lower
      concentration of flecainide than did the adult preparations. These findings may,
      in part, be the basis for the reported greater efficacy of the drug in children
      than in adults.

PMID- 9512873
TI  - A new platelet-activating factor antagonist (CV-6209) in preservation of heart
      and lung for transplantation.
AB  - The objective of this experimental protocol was to evaluate the protective effect
      of a new, potent platelet-activating factor (PAF) antagonist CV-6209 and the use
      of this compound in combination with allopurinol on ischemia-reperfusion injury
      in a swine model of heart-lung transplantation. Forty-two swine were divided into
      three groups, with seven donors and seven recipients in each. In group A, the PAF
      antagonist CV-6209 was administered in a single dosage of 1 mg/kg by slow
      intravenous injection at 1 hour before crossclamping of the aorta in both donors
      and recipients. In group B the combination of allopurinol and the PAF antagonist
      CV-6209 was used. Allopurinol was administered as a pretreatment regime of 50
      mg/kg/day for 3 days prior to ischemia. The PAF antagonist dosage and regime of
      administration were the same as in group A, and both donors and recipients were
      pretreated with this combination. Group C was the control in which heart-lung
      transplantations were performed without interventional therapies. Based on the
      comparison of pre- and post-transplantation assessments of cardiac and pulmonary
      functional integrity within groups, and post-transplantation among groups,
      animals in groups A and B were significantly (P < 0.05) better protected from
      ischemia-reperfusion injury than animals in group C. The difference between
      groups A and B, however, was insignificant at all times. Morphological findings
      are in agreement with measures of physiological variation among experimental
      groups. It is suggested that the new PAF antagonist CV-6209 is effective in the
      prevention of heart and lung ischemia-reperfusion injury with and without
      allopurinol pretreatment.

PMID- 9512874
TI  - Short-term treatment with low-dose pravastatin attenuates oxidative
      susceptibility of low-density lipoprotein in hypercholesterolemic patients.
AB  - The effects of treatment with low-dose 3-hydroxy-3-methylglutaryl-coenzyme A
      reductase inhibitor pravastatin on the changes of chemical composition and in
      vitro oxidative susceptibility of low-density lipoprotein (LDL) were studied in
      20 type Ila hyperlipidemic patients with a plasma total cholesterol level > 240
      mg/dL at the end of a diet control period for 3 months using the American Heart
      Association recommended step I diet. Treatment with pravastatin in a dose of 5 mg
      twice daily for 4 weeks resulted in lowering plasma total and LDL cholesterol
      levels by 17.0% and 22.9%, respectively. There was no further decline in plasma
      lipid thereafter. Chemical composition analysis showed that LDL particles did not
      contain significantly less cholesterol and thiobarbituric acid reactive
      substances (TBARS) until the end of 8 weeks (130.6 +/- 17.8 vs. 106.6 +/- 37.1
      mg/mg protein, P < 0.05 and 0.16 +/- 0.06 vs. 0.08 +/- 0.02 nmol/mg protein, P <
      0.005, respectively). Vitamin E, phospholipid, and triglyceride contents remained
      at the same levels throughout the study. In terms of oxidative kinetics, lag time
      and time to maximal diene concentration were not prolonged during the treatment
      period for 12 weeks, while total diene concentration and reaction rate were not
      significantly reduced until 8 weeks of treatment. Plasma enzyme activity of
      glutathione reductase and peroxidase, as well as the whole blood level of reduced
      and oxidized glutathione, remained similar during the study. In conclusion,
      pravastatin, at the low dose of 5 mg twice daily, produced a significant decline
      in plasma lipid levels to a steady-state range by 4 weeks; however, 8-weeks
      treatment is necessary to reduce the cholesterol and TBARS content, as well as to
      attenuate the oxidative susceptibility of LDL. These effects are not related to
      the antioxidant glutathione.

PMID- 9512875
TI  - Effect of hypotensive drugs on the circadian blood pressure pattern in essential
      hypertension: a comparative study.
AB  - To compare the effect of four drug groups on the ambulatory circadian blood
      pressure (BP) pattern, amiloride hydrochlorothiazide, atenolol, nifedipine, and
      perindopril (5/50 mg/d, 100 mg/d, 40 mg/d, and 4 mg/d respectively, for 14 days)
      were alternated in each of 20 essential hypertension patients. Diuretics induced
      the largest (P < 0.05) drop in mean 24-hour systolic BP (-12 mmHg, P < 0.001).
      Atenolol reduced only its standard deviation, and nifedipine reduced only the
      mean daytime systolic BP (P < 0.05). The mean 24-hour diastolic BP was equally
      reduced by all drugs except nifedipine, which only reduced (P < 0.05) the mean
      daytime value. The mean 24-hour heart rate was decreased by atenolol (P < 0.001),
      increased by diuretics (P < 0.05), and unchanged with perindopril, while
      nifedipine increased (P < 0.05) only its night-time value. In conclusion,
      diuretics were the strongest agents in reducing systolic BP, atenolol the only
      agent that reduced variability, perindopril the only agent that did not affect
      the heart rate, and nifedipine reduced only daytime BP values.

PMID- 9512876
TI  - Neuropeptide Y Y1 receptor antagonist (BIBP 3226) attenuates stress evoked
      tachycardia in conscious spontaneously hypertensive rats.
AB  - The effects of a novel neuropeptide Y (NPY) Y1 receptor antagonist on resting
      mean blood pressure (MBP) and heart rate (HR) were observed in conscious
      spontaneously hypertensive rats (SHR). The interference of the antagonist with
      cardiovascular responses to mental stress and administration of exogenous NPY
      were also investigated. SHR were randomly received either the NPY Y1 receptor
      antagonist (BIBP 3226; n = 11) or its inactive enantiomer (BIBP 3435; n = 11) as
      an infusion (6 mg/kg/h for 1.5 hours). Before, during, and after the infusion,
      rats were first stressed with a jet of air and then given a bolus injection of
      exogenous NPY (2 nmol/kg). There was no statistically significant difference of
      resting MBP and HR between the antagonist and enantiomer groups before, during,
      or after infusion. The stress-induced maximum increase in HR was significantly
      reduced during antagonist infusion (P < 0.05). The effects of exogenous NPY on
      both MBP and HR were significantly attenuated by antagonist infusion (P < 0.05,
      respectively), and the effect lasted at least 1 hour after the end of the
      infusion. Plasma catecholamine levels in response to stress were not
      significantly different between the two groups. The results suggest that
      endogenous NPY Y1-receptor mechanisms may be of minor importance in short-term
      regulation of MBP and HR in conscious adult SHR, but may be involved in the
      response to mental stress.

PMID- 9512877
TI  - Mixing with society.

PMID- 9512878
TI  - Biosynthesis of the ansamycin antibiotic rifamycin: deductions from the molecular
      analysis of the rif biosynthetic gene cluster of Amycolatopsis mediterranei S699.
AB  - BACKGROUND: The ansamycin class of antibiotics are produced by various
      Actinomycetes. Their carbon framework arises from the polyketide pathway via a
      polyketide synthase (PKS) that uses an unusual starter unit. Rifamycin (rif),
      produced by Amycolatopsis mediterranei, is the archetype ansamycin and it is
      medically important. Although its basic precursors (3-amino-5-hydroxy benzoic
      acid AHBA, and acetic and propionic acids) had been established, and several
      biosynthetic intermediates had been identified, very little was known about the
      origin of AHBA nor had the PKS and the various genes and enzymes that modify the
      initial intermediate been characterized. RESULTS: A set of 34 genes clustered
      around the rifK gene encoding AHBA synthase were defined by sequencing all but 5
      kilobases (kb) of a 95 kb contiguous region of DNA from A. mediterranei. The
      involvement of some of the genes in the biosynthesis of rifamycin B was examined.
      At least five genes were shown to be essential for the synthesis of AHBA, five
      genes were determined to encode the modular type I PKS that uses AHBA as the
      starter unit, and 20 or more genes appear to govern modification of the
      polyketide-derived framework, and rifamycin resistance and export. Putative
      regulatory genes were also identified. Disruption of the PKS genes at the end of
      rifA abolished rifamycin B production and resulted in the formation of P8/1-OG, a
      known shunt product of rifamycin biosynthesis, whereas disruption of the orf6 and
      orf9 genes, which may encode deoxysugar biosynthesis enzymes, had no apparent
      effect. CONCLUSIONS: Rifamycin production in A. mediterranei is governed by a
      single gene cluster consisting of structural, resistance and export, and
      regulatory genes. The genes characterized here could be modified to produce novel
      forms of the rifamycins that may be effective against rifamycin-resistant
      microorganisms.

PMID- 9512879
TI  - Prevalence and disease associations of certain autoantibodies in elderly
      patients.
AB  - OBJECTIVE: To determine the prevalence and association with various diseases of
      certain autoantibodies among elderly patients, in order to challenge the
      hypothesis that these autoantibodies are elevated generally in these patients as
      a result of immunosenescence. DESIGN: Prospective prevalence study. PATIENTS: A
      total of 399 elderly patients: 63 aging successfully (without chronic illness),
      301 with a variety of chronic general illnesses (frail elderly) and 35 with a
      clinical diagnosis of rheumatoid arthritis. These were compared with 250 healthy
      adult blood donors. INTERVENTIONS: Measurement of autoantibodies to rheumatoid
      factor, antinuclear antibody, double-stranded (native) DNA (nDNA), extractable
      nuclear antigens and anticardiolipin antibodies. OUTCOME MEASURES: Prevalence of
      these autoantibodies and correlation with disease states. RESULTS: Antibodies to
      rheumatoid factor and antinuclear antibody were significantly more prevalent in
      the elderly patients with chronic illness or rheumatoid arthritis but were not
      disease-specific. The prevalence of nDNA and extractable nuclear antigens was not
      increased in either the healthy or frail elderly groups. Anticardiolipin
      antibodies were significantly more prevalent in the frail elderly group when
      compared with normal controls and the healthy elderly group. The prevalence of
      anticardiolipin antibodies correlated with clinical features of cerebrovascular
      disease, in particular multi-infarct dementia and stroke, but not with
      Alzheimer's disease. CONCLUSIONS: The prevalence of the autoantibodies measured
      was not elevated in healthy elderly subjects, and autoantibodies such as nDNA and
      extractable nuclear antigens are specific to disease states in all groups of
      elderly patients. Anticardiolipin antibodies correlate with cerebrovascular
      events. Therefore, the clinical significance of autoantibodies in elderly
      patients is related more to global health status than to the effects of aging.

PMID- 9512880
TI  - Parental willingness to enter a child in a controlled vaccine trial.
AB  - OBJECTIVE: To determine the reasons that motivate parents to enrol or not enrol
      their child in a randomized, controlled vaccine trial. DESIGN: Cross-sectional
      survey. SETTING: Offices of primary care physicians in Dartmouth, Nova Scotia,
      and Montreal, Quebec. PARTICIPANTS: At the 2 sites, parents of 2-month-old
      infants at their first immunization visit who had decided to enrol (221) or not
      enrol (208) their child in 2 randomized pertussis vaccine trials. OUTCOME
      MEASURES: Rates of enrolment in vaccine trials; attitudes about medical research;
      sources of information about pertussis. RESULTS: Enrolment rates were 68% and 43%
      at the 2 sites. All parents agreed to answer questions about their decision to
      enrol or not enrol their child. The most common concerns resulting in
      nonenrolment were extra immunization 54% (26/48) and blood procurement 42%
      (20/48). Parents who did enrol their children were motivated to participate by
      the desire to contribute to medical knowledge (77% [170/221]), the desire to help
      others (48% [106/221]) and by the participation of their family physician (54%
      [120/221]). The enrollees' major sources of information about pertussis was
      health professionals or study personnel rather than the media. CONCLUSIONS:
      Altruistic reasons motivate parents' decision to enrol a child in a randomized,
      controlled vaccine trial. Nonparticipating parents seem most concerned about
      painful procedures in the study. Parents' decisions regarding participation do
      not appear to be affected by adverse media attention regarding the purported
      adverse sequelae of pertussis vaccines.

PMID- 9512881
TI  - Assessing the interpretation of criteria for clinical trial eligibility: a survey
      of oncology investigators.
AB  - OBJECTIVE: To investigate whether eligibility criteria that exclude the elderly,
      persons with psychiatric disease, and persons with substance abuse problems from
      participation in randomized controlled trials (RCTs) are subjective and hence a
      source of variability in enrolment decisions and investigator uncertainty.
      DESIGN: Survey questionnaire. PARTICIPANTS: Cancer investigators from the United
      States and Canada. INTERVENTIONS: Investigators were presented with clinical
      vignettes from 3 patient categories--eligible, ineligible and uncertain--for each
      of 5 eligibility criteria--3 subjective and 2 objective--and were asked whether
      they would enrol the patient in a trial and how sure they were of this decision.
      Demographic characteristics of the investigators were also collected. OUTCOME
      MEASURES: The difference in enrolment decisions between subjective and objective
      criteria, and the difference in the certainty associated with these decisions.
      RESULTS: Of 365 questionnaires sent out, 224 usable ones were returned. Compared
      with the objective criteria, the subjective criteria were associated with more
      variable enrolment decisions (p = 0.07 for the "eligible" scenario and p = 0.0001
      for the "ineligible" and "uncertain" scenarios), and investigators were less sure
      about the decisions they made (p = 0.0001 for all scenarios). Demographic
      characteristics of the investigators failed to explain the observed differences.
      CONCLUSIONS: Subjective eligibility criteria may interfere with the conduct and
      interpretation of RCTs and, therefore, their use ought to be justified explicitly
      in the study protocol. RCT designers, funding agencies and research ethics boards
      have an important role in reviewing eligibility criteria for their necessity.

PMID- 9512882
TI  - Relation between hospital HIV/AIDS caseload and mortality among persons with
      HIV/AIDS in Canada.
AB  - OBJECTIVE: To assess the relation between HIV/AIDS hospital caseload and
      mortality in Canada. DESIGN: Descriptive, population-based study. SETTING: All
      hospitals in Canada that admitted any patients with HIV or AIDS between Mar. 31,
      1987, and Apr. 1, 1994. PATIENTS: All patients with a diagnostic code on their
      hospital discharge abstract for HIV infection, AIDS, or with positive serological
      or viral culture findings for HIV (International Classification of Diseases, 9th
      revision, 042, 043, 044 or 795.8). MAIN OUTCOME MEASURE: In-hospital mortality.
      RESULTS: Over the study period, 38,075 admissions attributed to HIV/AIDS (33,380
      of men and 4695 of women) were recorded in 513 Canadian hospitals. Of these
      hospitals, 230 (45%) had fewer than 1 admission per year of patients with
      HIV/AIDS; 200 (39%) had between 1 and 9; 68 (13%) had between 10 and 99; and 15
      (3%) had 100 or more. HIV/AIDS-related admissions ending in death were
      independently associated with the patient being admitted to lower-volume
      hospitals, being hospitalized for longer periods of time, and being older, male
      and at a more advanced stage of disease. During the study period, hospitals with
      100 or more admissions per year reported 36% lower mortality among patients with
      HIV/AIDS than those that had fewer than 1 admission per year. CONCLUSION: There
      is an inverse relation between hospital caseload and in-hospital mortality among
      patients with HIV/AIDS in Canada. We attribute this association at least in part
      to the propensity of high-volume hospitals to deal more effectively with
      seriously ill patients with HIV/AIDS.

PMID- 9512883
TI  - Non-diabetic end-stage renal disease among Saskatchewan aboriginal people.
AB  - OBJECTIVE: To determine the rates, causes and outcomes of non-diabetic end-stage
      renal disease (ESRD) among aboriginal and non-aboriginal people in Saskatchewan.
      DESIGN: Retrospective population-based study using data from the Canadian Organ
      Replacement Register. SETTING: Saskatchewan. SUBJECTS: All patients with non
      diabetic ESRD diagnosed between Jan. 1, 1981, and Dec. 31, 1990. MAIN OUTCOME
      MEASURES: Age- and sex-specific as well as age-adjusted incidence rates of non
      diabetic ESRD among aboriginal and non-aboriginal people in Saskatchewan, causes
      of non-diabetic ESRD, mortality rates, causes of death and renal transplantation
      rates. RESULTS: The 10-year incidence rates of non-diabetic ESRD were higher in
      all age groups among aboriginal people than among non-aboriginal people. The
      overall risk ratio for aboriginal people was 2.56. Aboriginal people experienced
      non-diabetic ESRD at an earlier age and were twice as likely to have a form of
      glomerulonephritis as a cause. Crude mortality rates, causes of death and
      transplantation rates were similar in the 2 populations, although we were unable
      to adjust these for differences in age. CONCLUSION: Although diabetes is the most
      common cause of ESRD among aboriginal people in Saskatchewan, this population
      also experiences an excessive burden of non-diabetic ESRD, which is largely
      explained by a higher rate of glomerulonephritis.

PMID- 9512884
TI  - "Scientists Inc."--illusion or disillusion?

PMID- 9512885
TI  - Identification of lysyl oxidase and TRAMP as the major proteins in dissociative
      extracts of the demineralized collagen matrix of porcine dentine.
AB  - Carbonated apatite (dahllite) is formed within and between collagen fibrils in
      the mineralization of connective tissues. However, the mechanism of crystal
      nucleation at these sites has not been resolved. To identify non-collagenous
      proteins that may be involved in the nucleation process we have utilized a
      dissociative extraction procedure to isolate proteins associated non-covalently
      with the de-mineralized collagen matrix of dentine isolated from tooth roots of
      adult porcine incisors. Following extraction of dentine fragments with 4M GuHCl
      (G1-extract) and 0.5M EDTA (E-extract), de-mineralized collagen matrix-associated
      proteins were isolated with a second series of extractions with 4M GuHCl (G2
      extract). Analysis of the G2-extracts on SDS-PAGE revealed two major 32 kDa and
      24 kDa protein bands, comprising > 80% of the extracted non-collagenous proteins.
      The 32 kDa protein was purified by FPLC on hydroxyapatite and Mono Q resins,
      followed by HPLC reverse-phase chromatography. Small amounts of 26 kDa and 6 kDa
      proteins, which appear to represent proteolytically processed, disulphide-linked
      fragments of the 32 kDa protein, co-eluted with the major protein. The 32 kDa
      protein was identified as lysyl oxidase from amino acid sequence analysis of a 13
      kDa CNBr peptide obtained from protein purified by preparative electrophoresis on
      SDS-PAGE. Fractionation of the 24 kDa protein on FPLC Mono Q resin generated < 5
      closely eluting protein peaks. The proteins from these peaks were similar in
      size, staining properties, amino acid composition and CNBr digestion patterns.
      Each protein was immunoreactive with antibodies raised against a tyrosine-rich
      acidic matrix protein (TRAMP), reported previously to co-purify with lysyl
      oxidase. These studies, therefore, show that lysyl oxidase, which is important in
      collagen cross-link formation, and proteins with properties of TRAMP, a protein
      that can modulate collagen fibrillogenesis, are the major proteins in
      dissociative extracts of de-mineralized porcine dentine.

PMID- 9512886
TI  - Organization of fibrillar collagen in the human and bovine cornea: collagen types
      V and III.
AB  - The localization and fibrillar organization of collagen types V and III in the
      human and bovine corneal stromas were studied. In the chicken cornea, type V co
      assembles with type I collagen as heterotypic fibrils and this interaction is
      involved in the regulation of fibril diameter necessary for corneal transparency.
      To determine whether this is a regulatory mechanism common to the corneas of
      different species the human and bovine corneal stroma were studied. Collagen type
      V was found in the epithelium and Bowman's membrane in the untreated adult human
      and bovine cornea using immunofluorescence microscopy. In the absence of any
      treatment, there was no type V reactivity within the stroma. However, type V
      collagen was detected homogeneously throughout the corneal stroma after
      treatments that partially disrupt fibril structure. The reactivity was strongest
      in the cornea, weaker in the limbus and weakest in the sclera. Fetal corneas
      showed similar reactivity for type V collagen, but unlike the adult, the stroma
      was slightly reactive. Immunoelectron microscopy demonstrated that type V
      collagen was associated with disrupted, but not with intact, fibrils in both
      human and bovine corneal stroma. Type III collagen reactivity was not detected in
      the cornea, but was present subepithelially in the limbus and in the scleral
      stroma. These data indicate that type V collagen is a component of striated
      collagen fibrils throughout the human and bovine corneal stromas. The interaction
      of type I and V collagen as heterotypic fibrils masks the helical epitope
      recognized by the monoclonal antibody against type V collagen. The heterotypic
      interactions of collagen type V indicate a role in the regulation of fibril
      diameter analogous to that described in the avian cornea.

PMID- 9512887
TI  - Dermatan sulfate proteoglycans from the mineralized matrix of the avian eggshell.
AB  - The eggshell of the chicken is a useful model to study matrix components which
      affect biomineralization. As an extension of our previous immunohistochemical
      work which suggested the presence of dermatan sulfate proteoglycans in the
      mineralized region of the eggshell, a study was undertaken to characterize these
      molecules biochemically. After demineralization with HCl and extraction with 4 M
      guanidinium chloride containing protease inhibitors, the extract was partitioned
      by anion exchange chromatography. Step elution with 0.25 M and 1.0 M sodium
      chloride resulted in the generation of two fractions, both of which contain
      chondroitinase-sensitive proteoglycans with molecular weights estimated at
      200,000 by gel electrophoresis. The proteoglycans in each fraction have core
      proteins with molecular weights of approximately 120,000 and glycosaminoglycans
      with average molecular weights of 22,000. Based on differential sensitivity to
      chondroitinase ABC and AC II, these glycosaminoglycans contain a small proportion
      of dermatan sulfate. The disaccharide compositions of these glycosaminoglycans
      differ for the proteoglycans eluted with 0.25 M and 1.0 M sodium chloride. Those
      eluted with lower sodium chloride are enriched in unsulfated chondroitin and have
      much more 4-sulfated than 6-sulfated disaccharides; those eluted with 1.0 M
      sodium chloride contain primarily 4-sulfated disaccharides, a small amount of 6
      sulfated disaccharides, and less unsulfated disaccharides than the proteoglycans
      eluted with 0.25 M sodium chloride. The large difference in the proportions of
      unsulfated chondroitin may be the reason for the elution at different sodium
      chloride concentrations. Both of the anion exchange column fractions contain
      other proteins in addition to the proteoglycans. These proteins are not separated
      from the proteoglycans by a second anion exchange column or by molecular sieve
      chromatography under dissociative conditions. Of particular interest is the
      observation that the eggshell proteoglycans and their core proteins are
      recognized by a monoclonal antibody which recognizes an epitope on the core
      protein of avian versican. This suggests that, in spite of the large differences
      in the sizes of the core proteins of versican and the eggshell proteoglycans,
      these core proteins share some homology. Because anionic molecules are thought to
      be important regulators of biomineralization, and because preparations like those
      analyzed in this study have been shown to influence in vitro calcium carbonate
      crystallization, the eggshell proteoglycans may play a role in eggshell
      mineralization.

PMID- 9512888
TI  - Precursor matrix proteins in the uterine fluid change with stages of eggshell
      formation in hens.
AB  - Organic constituents of the uterine fluid, the acellular milieu in which the
      eggshell is mineralized, were biochemically characterized at initial, mid and
      final stages of shell calcification in hens. The electrophoretic protein profiles
      changed at the different stages of shell mineralization. Two major bands (80-kDa
      and 43-kDa glycoproteins) with calcium affinity were specific to the initial
      stage. Four protein bands of 180, 150, 116 and 32 kDa, present at the phase of
      rapid shell formation, coprecipitated with calcium carbonate in vitro. At this
      stage were also present a calcium-binding glycoprotein of 36-kDa and a 20-kDa
      protein. Uterine fluid of the final stage was characterized by a darker intensity
      of the 66-kDa band, which showed calcium-binding ability and by the presence of
      three additional proteins (72, 13 and 6 kDa). At least seven bands of the uterine
      fluid showed similar migration patterns to those of eggshell extracts. Western
      blotting with ovocleidin and ovalbumin antisera demonstrated the presence of
      these matrix proteins in uterine fluid collected at initial and mid phase,
      respectively. Total uterine fluid collected at the end of calcification and
      dialyzed uterine fluid from the various stages delayed the rate of calcium
      precipitation in vitro. These observations demonstrate the presence of precursors
      of eggshell matrix in the uterine fluid and support the hypothesis of their
      involvement in the process of eggshell mineralization.

PMID- 9512889
TI  - Partial biochemical and immunologic characterization of fibrillin microfibrils
      from sea cucumber dermis.
AB  - The dermis of the sea cucumber Cucumaria frondosa is a mutable collagenous tissue
      composed of collagen fibrils, microfibrils, proteoglycans, and other soluble and
      insoluble components. A major constituent of the dermis is a network of 10-14 nm
      microfibrils which surrounds and penetrates bundles of collagen fibrils. These
      microfibrils, which are morphologically very similar to the fibrillin
      microfibrils of vertebrates, were found to be insoluble in protein denaturants,
      including chaotropic agents and ionic and nonionic detergents, regardless of the
      reduction of disulfide bonds. The microfibrils are covalently crosslinked by
      epsilon-(gamma-glutamyl)lysine at a concentration of 3.725 nmol/mg dry weight of
      purified insoluble material. The network is susceptible to proteolysis by
      trypsin, chymotrypsin, and pancreatic elastase, but not by bacterial collagenase.
      Amino acid compositional analysis of the network shows it to be composed of 25%
      ASX and GLX residues. Comparison with the proteins in the SwissProt database
      gives the network protein a high probability of being related to the mammalian
      protein fibrillin. The network is glycosylated: approximately 7% of the mass is
      constituted by neutral and amino sugars. The intact microfibrillar network cross
      reacted with a well-characterized antiserum to mammalian fibrillin.

PMID- 9512890
TI  - Detection of tubulointerstitial nephritis antigen (TIN-ag) in Lewis rat.
AB  - Tubulointerstitial nephritis antigen (TIN-ag) is a recently described basement
      membrane component reactive with autoantibodies in some forms of autoimmune
      mediated tubulointerstitial nephritis. Immunofluorescence studies using
      polyclonal and monoclonal antibodies have indicated a restrictive tissue
      distribution for TIN-ag, with the site of most prominent expression the kidney
      tubular basement membrane. However, Lewis rat does not demonstrate any
      immunoreactivity for TIN-ag and does not develop tubuloinsterstitial nephritis
      after injection of tubular basement membrane material. As TIN-ag would appear to
      be a molecule of biological significance, experiments were designed to explore
      the presence or absence of this macromolecule in the Lewis rat model. Southern
      blotting of Lewis rat genomic DNA revealed the presence of gene sequences
      corresponding to TIN-ag. RTPCR analysis of Lewis rat kidney cortex total RNA
      illustrated the expression of a TIN-ag gene product. Western blotting
      demonstrated the presence of TIN-ag protein forms in kidney cortical homogenates
      of Lewis rat. The data suggest either extensive epitope masking or expression
      polymorphism of TIN-ag in the Lewis rat.

PMID- 9512891
TI  - Glycosaminoglycan metabolism and cytokine release in normal and otosclerotic
      human bone cells interleukin-1 treated.
AB  - Glycosaminoglycans (GAGs), normal components of the extracellular matrix (ECM),
      and the glycosidases, that degrade them, play a key role in the bone remodelling
      process. The effects of interleukin-1 alpha (IL-1 alpha) on GAG metabolism in
      normal and otosclerotic human bone cells as well as its capacity to modulate IL-1
      alpha, IL-1 beta and IL-6 secretion in both populations was analyzed. The amount
      of radiolabeled GAGs was lower in otosclerotic than in normal bone cells. IL-1
      alpha reduced newly synthesized cellular and extracellular GAGs in normal cells,
      but only those of the cellular compartment in otosclerotic bone cells. It
      depressed heparan sulphate (HS) more in normal cells and chondroitin sulphate
      (CS) more in otosclerotic bone cells. The HA/total sulphated GAG ratio was
      shifted in favour of the latter in otosclerotic cells, whereas the opposite
      effect was seen after IL-1 alpha treatment. There was little difference in the
      beta-D-glucuronidase levels of the normal and pathological cells, while beta-N
      acetyl-D-glucosaminidase was significantly increased in otosclerotic bone cells.
      As the activity of neither enzyme was modified by treatment with IL-1 alpha, the
      cytokine seems to exert its influences on GAG synthesis rather than on the
      degradation process. IL-1 alpha, IL-1 beta and IL-6 secretion was markedly higher
      in otosclerotic cells. IL-1 alpha modulated the secretion of each interleukin
      differently, thus resulting in a cytokine cascade that may act in
      autocrine/paracrine manner on target cells. The authors suggest that changes in
      the cytokine network may have a specific, yet still unknown, role during normal
      and pathological osteogenesis.

PMID- 9512892
TI  - The nitrite/elastin reaction: implications for in vivo degenerative effects.
AB  - Nitrite ion is a by-product of nitrogen oxides (nitric oxide and nitrogen
      dioxide) from cigarette smoke and is used as a preservative for curing meats.
      Therefore, study of the reaction of nitrite with elastin in vitro was undertaken.
      By colorimetric assay, reactivity of nitrite with insoluble elastin at neutral
      pH, 37 degrees C, and physiologic concentration was confirmed. In histochemical
      studies on in situ human aortic elastin, nitrite-treated sections displayed
      marked structural disruptions. Determinations of fluorescence and absorbance on
      nitrite-treated soluble bovine elastin revealed marked alterations of
      fluorescence, and increased UV and visible absorbance. Amino acid analysis
      confirmed that it reacted with tyrosine. The findings indicate that non-enzymatic
      nitration by nitrite may have deleterious effects on elastin in vivo and may
      provide insights into the pathogenesis of chronic elastin degenerative processes,
      including aortic aneurysms, pulmonary emphysema, and premature skin wrinkling,
      all of which have been well known to have associations with cigarette smoking.

PMID- 9512893
TI  - An age-related study of morphology and cross-link composition of collagen fibrils
      in the digital flexor tendons of young thoroughbred horses.
AB  - The superficial digital flexor tendon is the most commonly injured tendon in the
      racing Thoroughbred. Despite the clinical significance of this structure, only
      limited data exist regarding normal age-related morphology of the tensile units,
      the collagen fibrils. The age at which these collagen fibrils become mature in
      composition and structure may be of importance. Consequently, the association of
      age and collagen fibril crosslink composition, diameter distribution and crimp
      morphology in the superficial and deep digital flexor tendons of Thoroughbreds up
      to and including three years of age has been studied. Replacement of immature
      crosslinks, peaking of the collagen fibril mass-average diameter and collagen
      fibril index, and stabilization of collagen crimp morphology changes supported
      the hypothesis that both digital flexor tendons become mature in structure by two
      years of age.

PMID- 9512894
TI  - Collagen fibril diameters in the rabbit medial collateral ligament scar: a longer
      term assessment.
AB  - Previous transmission electron microscopic investigations of collagen fibril
      diameters in rabbit medial collateral ligament (MCL) scars have indicated a
      homogeneous population of small fibrils for the first 40 weeks of healing. In
      this study, four 8 mm MCL gap scars were studied at 78 weeks of healing and
      another three at 104 weeks. Results showed increased heterogeneity in the
      distribution of fibril diameters in all scars, with the appearance of
      progressively slightly larger fibrils in 78 and 104 week specimens. All longer
      term scars still contained roughly 90% small fibrils plus some "patches" of
      larger fibrils, but there was considerable variation between animals in these
      proportions. No scar contained the fibril populations typical of uninjured adult
      rabbit MCLs. These results suggest slow but on-going collagen fibril turnover and
      remodeling in this gap healing rabbit MCL model via currently unidentified
      mechanisms.

PMID- 9512895
TI  - Microstructure and micromechanical properties of the mid-diaphyses of human fetal
      femurs.
AB  - The microstructure, composition and the micromechanical properties across the
      thickness of femoral mid-diaphyses from 14 to 26 week human fetuses have been
      investigated. Scanning electron microscopy and transmission electron microscopy
      were employed to examine structural changes with maturation. The fetal bones
      consist of layers of woven bone. From young to old fetuses and from outer to
      inner bone layers, the collagen fibrils become more cross-linked, densely packed
      and change from disordered to an ordered arrangement. The collagen fibril bundles
      are also more preferentially oriented and change from a chiefly circumferential
      to longitudinal direction. The sizes of the apatite crystals also increase with
      age. The Ca/P ratio remains constant around 1.55 for all the bone layers except
      the outmost layer which is lower than 1.2. An nano-indenter was used to evaluate
      the microhardness and elastic modulus of each bone layer. The increase of
      microhardness and elastic modulus correlates with the maturation of bone. The
      mechanical properties of the mid-diaphyses of human fetal femurs are anisotropic,
      which is due to the preferential orientation of collagen fibrils.

PMID- 9512896
TI  - Differential regulation of interleukin 4 and interleukin 13 production by
      interferon alpha.
AB  - Interferon alpha (IFN-alpha) has proven its clinical usefulness in a variety of
      diseases of diverse pathogenesis. In addition to direct antiviral effects, recent
      evidence suggests that its interaction with the cytokine cascade might contribute
      to its mechanism of action. This study was undertaken to determine whether IFN
      alpha influences the synthesis of interleukin 4 (IL-4) and IL-13, two cytokines
      which share many biological properties on various cells and tissues and which
      have a profound role in regulating immunological and inflammatory responses.
      Peripheral blood mononuclear cells (PBMC) from healthy volunteers were stimulated
      with Concanavalin A (ConA), phorbol myristate acetate (PMA), anti-CD3/CD28 mAbs,
      either alone or in various combinations, and incubated with increasing
      concentrations of IFN-alpha. IL-4 and Il-13 mRNA was determined by Northern
      hybridizations and IL-4 and IL-13 protein synthesis was evaluated by specific
      enzyme-linked immunosorbent assay (ELISA). IFN-alpha led to a profound decrease
      of IL-13 mRNA expression after an incubation period of 5 h with ConA alone or in
      combination with PMA, whereas it showed no regulatory effect on IL-4 mRNA
      expression. After an incubation period of 24 h, the decrease in IL-13 mRNA
      expression after addition of IFN-alpha was even more pronounced. At the protein
      level, IFN-alpha increased IL-4 synthesis dose dependently regardless of the mode
      of activation. This increase was most pronounced after stimulation with ConA or
      anti-CD28/PMA. In contrast, IL-13 synthesis was strongly downregulated by IFN
      alpha in a dose-dependent manner irrespective of the activating agent. It is
      concluded that IL-4 and IL-13, although showing similar biological effects, are
      differentially regulated by IFN-alpha.

PMID- 9512897
TI  - Involvement of 26-kDa membrane-bound tumour necrosis factor precursor in
      bidirectional feedback regulation on 17-kDa tumour necrosis factor production
      after stimulation by lipopolysaccharide.
AB  - The authors have previously shown that 26-kDa membrane-bound tumour necrosis
      factor precursor (proTNF) on the cell-surface of primed human monocytic cell line
      THP-1 is involved in positive feedback regulation of lipopolysaccharide (LPS)
      dependent TNF-production. Here, we provide direct evidence for modulation of
      responsiveness of the THP-1 cells against LPS by membrane-bound pro-TNF. When THP
      1 cells were cocultivated with a heterogeneous cell line (proTNF/3T3 cells) which
      constitutively expressed membrane-bound proTNF, LPS-dependent TNF-production by
      THP-1 cells was significantly suppressed and the normal level was restored by the
      presence of anti-TNF antibody during cocultivation. The proTNF-3T3-induced
      decline of TNF-production of THP-1 was observed primarily at the mRNA level,
      although no difference was observed in the mRNA level of interleukin 1 beta,
      another LPS-inducible cytokine. These results suggest that proTNF could also be
      involved in the negative feedback regulation of LPS-dependent TNF-production
      through cell-to-cell contact. The augmentation of LPS-dependent TNF-production
      accompanied by the production of endogenous proTNF induced by exogenous agent was
      inhibited by protein kinase C inhibitor, whereas proTNF/3T3-induced suppression
      of TNF-production could not be restored to the normal level. It thus seems
      possible that proTNF might act on macrophages as a bidirectional regulator of its
      production by THP-1 cells depending on co-induced signals.

PMID- 9512898
TI  - IL-6 and IL-8 production by human bone marrow stromal cells.
AB  - By using a specific enzyme-linked immunosorbent assay, the authors demonstrated
      that human bone marrow stromal cells produce IL-6 and IL-8. Their synthesis is
      enhanced in a dose-dependent manner after stimulation with lipopolysaccharide
      (LPS) and phorbol myristate acetate (PMA). Interleukin 6 (IL-6) and IL-8
      production in response to PMA were markedly diminished by the PKC inhibitor
      staurosporine. IL-6 (10 ng/ml) stimulated IL-8 production with 0% and 10% fetal
      calf serum (FCS) in the culture medium. In similar conditions, IL-8 (10 ng/ml)
      enhanced IL-6 production. IL-1 alpha, IL-1 beta, and IL-3, tumour necrosis factor
      alpha (TNF-alpha), Stem cell factor (SCF) and granulocyte-macrophage colony
      stimulating factor (GM-CSF) (at 10 ng/ml) stimulated IL-6 and IL-8 production in
      0% and 10% FCS. G-CSF stimulated and IL-4 inhibited IL-8 production in 10% FCS.
      IL-2, IL-4 and bFGF stimulated IL-6 production in 0% FCS. These results suggest
      that bone marrow stromal cells might represent a major source for the cytokine
      regulated local production of IL-6 and IL-8 inside human bone marrow.

PMID- 9512899
TI  - Oncostatin M stimulates macrophage-polykaryon formation in long-term human bone
      marrow cultures.
AB  - Though oncostatin M (OSM) is a potent mediator of the inflammatory reaction, its
      role in inflammation and bone resorption is still unclear. A long-term bone
      marrow culture system is usually developed to allow the formation of
      multinucleated cells (MNC) and was used here to define the effects of human
      recombinant OSM on human MNC formation. OSM significantly upregulated (1.9- to
      5.6-fold) the number of MNC in these cultures in a dose- and time-dependent
      manner. Cell nucleation and tartrate-resistant acid phosphatase activity were
      also increased. MNC did not display osteoclast characteristics, such as response
      to calcitonin and failure to resorb dentin surface. However, they expressed a non
      specific alpha-naphthyl acetate esterase as well as macrophage differentiation
      antigens (CD11b, CD13 and CD33) and were able to perform phagocytosis. Similar
      effects were observed after addition of 1 alpha, 25-dihydroxyvitamin D3.
      Moreover, in these culture conditions, human bone-marrow mononuclear cells were
      capable of low-grade resorption in the presence of bone-marrow stromal cells.
      This low-grade resorption was significantly inhibited by addition of 25 ng/ml
      OSM. Our data demonstrate for the first time that human recombinant OSM
      significantly stimulates the formation of MNC and could be involved in the
      inflammatory process via macrophage-polykaryon formation from human bone marrow.

PMID- 9512900
TI  - Increased levels of leukaemia inhibitory factor (LIF) in urine and tissue culture
      supernatant from human primary bone tumours.
AB  - Fifty-five adult patients with primary bone tumour, 27 benign and 28 malignant
      tumours, were assayed for leukaemia inhibitory factor (LIF) in urine and serum
      samples. Supernatant was obtained from primary tumour tissue cultures in 24 cases
      (14 benign, 10 malignant tumours). LIF was found in 11 urine samples (16.7%, 1
      benign and 10 malignant tumours). In 23 urine samples from patients with
      malignant bone tumour tested before any treatment, LIF was detectable in eight
      cases (34.7%). High LIF levels were found in all supernatants from malignant
      tumour cultures and in supernatant from 12 of the 14 benign tumours cultured. LIF
      was never detected in control urine samples or supernatants from normal cancelous
      bone cultures. These first in vivo data concerning LIF in primary bone tumours
      raise the question as to the cellular origin of this multifunctional cytokine and
      its potential role in solid bone tumours and bone tumour resorption.

PMID- 9512901
TI  - The role of endogenous IFN-gamma, TNF-alpha and IL-10 in LPS-induced nitric oxide
      release in a mouse model.
AB  - Mice injected with lipopolysaccharide (LPS) develop lethal septic shock,
      accompanied by elevated serum NOx, interferon gamma (IFN-gamma), tumour necrosis
      factor alpha (TNF-alpha) and TNF-receptor levels. Elevated NO levels are thought
      to play a central role in tissue damage observed during septic shock. In vitro
      data indicate that IFN-gamma and TNF-alpha play an important role in LPS-induced
      NO release. Further, interleukin 10 (IL-10) has been shown to inhibit the release
      of pro-inflammatory cytokines such as IFN-gamma and TNF-alpha. Therefore, in the
      present study, we investigated the role of IFN-gamma, TNF-alpha, and IL-10 in LPS
      induced NO release. To this end, mice were pretreated with anti-IFN-gamma, anti
      TNF-alpha, anti-IL-10 mAbs or combinations of these 2 h before LPS-challenge. The
      results indicate that IFN-gamma, TNF-alpha as well as IL-10 are involved in the
      regulation of LPS-induced NO release. Blocking either IFN-gamma or TNF-alpha has
      no effect on LPS-induced NO release, however, blocking both IFN-gamma and TNF
      alpha nearly completely prevents NO release after LPS challenge, suggesting that
      the presence of either TNF-alpha or IFN-gamma is essential for induction of NO
      release after LPS challenge. Further, the results obtained with anti-IL-10
      treatment suggest the presence of an IL-10 inducible factor which together with
      IFN-gamma and TNF-alpha regulates LPS-induced NO release.

PMID- 9512902
TI  - Molecular pathogenesis of interstitial pneumonitis with TNF-alpha transgenic
      mice.
AB  - Tumour necrosis factor alpha (TNF-alpha) transgenic mice, which overexpress TNF
      alpha in the lungs, develop interstitial pneumonitis resembling idiopathic
      pulmonary fibrosis (IPF) in humans. Transgenic mice were used to study molecular
      pathogenesis of interstitial pneumonitis with regard to sequential histological
      changes and cytokine network induced by TNF-alpha. The authors divided the
      histological process of interstitial pneumonitis into three stages: early stage
      with lymphocytic infiltration in alveolar septa, middle stage with recruitment of
      macrophages, and late stage with hyperplasia of epithelial cells and mild
      fibrosis. As for cytokine network, prolonged overexpression of TNF-alpha along
      with increasing interleukin 6 (IL-6) were associated with the progression of
      interstitial pneumonitis. Increasing IL-1 was found only in the early stage, the
      beginning of lymphocyte proliferation. The mRNA level of an anti-inflammatory
      cytokine, IL-10, was constantly enhanced in the lungs of transgenic mice.
      However, transforming growth factor beta 1 (TGF-beta 1) protein decreased, which
      is closely associated with prolonged TNF-alpha synthesis, resulting in
      development of chronic inflammation and less severe fibrosis in the lungs of this
      animal model, analogous to inflammatory stage of human IPF. TNF-alpha transgenic
      mice enabled the analysis of the sequential process of interstitial pneumonitis
      as a model of IPF pathogenesis in humans, the results of which will give rise to
      new therapeutic measures for human IPF.

PMID- 9512903
TI  - Generation of human lymphokine-activated killer cells following an IL-2 pulse in
      elderly cancer patients.
AB  - The toxicity of high-dose interleukin 2 (IL-2) treatments limits its use in
      tumour therapies, particularly in older age groups, characterized by a reduced
      tolerance to antineoplastic therapies. Here, we evaluated the possibility to
      induce cytotoxic lymphokine-activated killer (LAK) cells through a brief exposure
      (1-h pulse) of peripheral blood mononuclear cells (PBMC) from elderly cancer
      patients to high concentrations of IL-2. The cytotoxic activity, phenotype,
      apoptosis, and cell cycle phase of IL-2 pulsed PBMC were determined and compared
      with those of non-pulsed PBMC cultured continuously in IL-2. Significant levels
      of LAK cytotoxicity were obtained in pulsed PBMC from all patients examined. The
      mean values of lytic activity on day 6 of culture were lower, even if not
      significantly, in pulsed than non-pulsed cultures. The pulsed cells were
      phenotypically similar to non-pulsed lymphocytes with regards to the expression
      of CD3, CD4, CD8, CD16, and CD56 antigens. The induction of activation markers,
      like CD25 and CD122 IL-2 receptors and CD71 transferrin receptor, was also
      comparable in pulsed and non-pulsed cultures. When a lower cytotoxicity was found
      in pulsed cultures, a lower number of CD54+ (ICAM-1) cells was also found. LAK
      cell cytotoxicity and number of CD54 cells were significantly correlated. No
      difference was found between pulsed and non-pulsed cultures in their cell cycle
      phase or in the percentage of apoptotic cells. Autologous plasma did not inhibit
      the differentiation of pulsed PBMC into LAK cells. The IL-2 pulse of PBMC from
      healthy young donors resulted in the induction of LAK cytotoxicity as observed in
      elderly cancer patients. The results demonstrate the effectiveness of IL-2 pulse
      to generate cytotoxic LAK cells in elderly cancer patients suggesting the
      potential application of pulsing procedures to treatment of older age groups.

PMID- 9512904
TI  - Impaired production of IL-12 in systemic lupus erythematosus. I. Excessive
      production of IL-10 suppresses production of IL-12 by monocytes.
AB  - Interleukin 12 (IL-12) plays a crucial role in defensive immune responses,
      modulation of cytokine production and is involved in the pathogenesis of some
      autoimmune diseases. The authors investigated whether decreased in vitro
      production of IL-12 occurs in systemic lupus erythematosus (SLE), in which the
      cytokine secreting pattern is predominantly type 2. IL-12 production by SLE
      peripheral blood mononuclear cells (PBMC) was significantly impaired compared
      with normal PBMC, and this was not due to decreased numbers of monocytes. After
      depletion of non-adherent cells from PBMC, monocytes of SLE patients produced
      significantly less IL-12 than those of controls, but IL-12 levels in SLE and
      control non-adherent cells supernatants were not significantly different.
      Exogenous recombinant (r)IL-10 strongly inhibited IL-12 production by both SLE
      and normal PBMC and anti-IL-10 neutralizing antibody significantly reversed the
      IL-12 deficiency of SLE PBMC and SLE monocytes, while not affecting normal PBMC.
      Recombinant interferon gamma (rIFN-gamma) considerably enhanced IL-12 production
      in both SLE and normal PBMC, but it did not significantly reverse the inhibitory
      effect of rIL-10 on IL-12 production. IL-12 production was significantly lower in
      patients with active SLE than those in remission. These results suggest that SLE
      monocytes may be deficient in IL-12 production and that this is secondary to
      abnormal production of various cytokines, especially excessive production of IL
      10.

PMID- 9512905
TI  - Impaired production of IL-12 in system lupus erythematosus. II: IL-12 production
      in vitro is correlated negatively with serum IL-10, positively with serum IFN
      gamma and negatively with disease activity in SLE.
AB  - Interleukin 12 (IL-12) is a key cytokine in regulating type 1 or type 2 cytokine
      production and in determining the nature of immune responses. Our previous
      studies demonstrated that its production was significantly impaired in systemic
      lupus erythematosus (SLE) patients and this deficient IL-12 production was mainly
      mediated by excessive endogenous IL-10. The present study was designed to further
      reveal the relationships of in vitro IL-12 production with abnormalities of in
      vivo cytokine synthesis and disease activity in SLE. Experimental results showed
      that IL-12 production in vitro was inversely correlated with serum IL-10 level,
      anti-ds DNA antibody level and SLE disease activity index (DAI), but positively
      correlated with serum interferon gamma (IFN-gamma) level, with which serum IL-10
      correlated negatively. Data also showed that serum IL-10 was significantly higher
      than that of controls and closely correlated with anti-ds DNA antibody level and
      SLEDAI. The study confirms that deficient IL-12 production in SLE patients is
      associated with in vivo abnormalities of cytokine production, especially with
      increased IL-10 production.

PMID- 9512906
TI  - Reconstructing the size of the African American population by age and sex, 1930
      1990.
AB  - We estimate the size of the African American population in five-year age groups
      at census dates from 1930 to 1990 using a three-part strategy. For cohorts born
      after 1935, we follow the U.S. Census Bureau in using classical demographic
      analysis. To estimate the size of cohorts born before 1895, we use extinct
      generation estimates. For remaining cohorts, we implement an age/period/cohort
      model of census counts. All approaches are applied to a data set in which the age
      distribution of deaths has been corrected for age misreporting. Results provide
      strong confirmation of the basic validity of Census Bureau estimates of census
      undercounts for African Americans while extending estimates to new cohorts and
      periods. Our estimates are less consistent with an historical series prepared by
      Coale and Rives (1973).

PMID- 9512908
TI  - Changes in racial identification and the educational attainment of American
      Indians, 1970-1990.
AB  - We use data from the 1970, 1980 and 1990 census public-use files to assess the
      impact of newly identified Indians on the educational attainment of American
      Indians who were at least 25 years old in 1970. We test the hypotheses that this
      impact was limited to metropolitan areas and to states with small Indian
      populations. We find that educational attainment for American Indians rose
      sharply between 1970 and 1990 and that changes in racial identification were an
      important component of this increase in 1980 but not in 1990. Increases in
      educational attainment were concentrated in metropolitan areas and occurred in
      states with large and small Indian populations.

PMID- 9512909
TI  - Population growth and air quality in California.
AB  - Demographers are often interested in the environmental impacts of population
      growth. I examine the impact of growth specifically on air quality in California.
      In recent decades, California has suffered from notoriously polluted air and has
      experienced rapid population growth. Despite the population growth, air quality
      actually has improved since the early 1980s due to aggressive regulatory efforts.
      Using data for 56 counties, I analyze the contribution of population growth to
      trends in atmospheric emissions of five regulated pollutants from 1980 to 1990,
      controlling for trends in per capita income and regulatory efforts. The analysis
      is disaggregated by source of emissions and demonstrates that population growth
      is strongly associated with some sources of emissions but not with others. Thus,
      the overall impact of population growth depends upon the composition of
      production and consumption activities in each county. I also explore whether the
      trend in number of households predicts better than the trend in number of
      persons, and whether the impact of population growth depends upon the age
      structure or source of growth (immigration or domestic increase). Generally,
      these alternative specifications of population do not improve the models of
      atmospheric emissions.

PMID- 9512907
TI  - The ecology of race and socioeconomic distress: infant and working-age mortality
      in Chicago.
AB  - We examine the effects of education, unemployment, and racial segregation on age
      , sex-, and race-specific mortality rates in racially defined Chicago community
      areas from 1989 to 1991. Community socioeconomic factors account for large
      observed areal variations in infant and working-age mortality, but especially
      working-age mortality for the black population. For black men, the mortality
      consequences of living in economically distressed communities are quite severe.
      Segregation effects on mortality are more modest and largely operate through
      neighborhood socioeconomic conditions, although some direct effects of
      segregation on mortality for blacks are apparent.

PMID- 9512910
TI  - Family size and children's education in Vietnam.
AB  - Data from the nationally representative 1994 Inter-Censal Demographic Survey are
      used to examine the association between family size and children's schooling in
      Vietnam. The data provide information on several education measures for all
      children over age 10, including children no longer residing in the household.
      Although a clear inverse bivariate association between family size and children's
      school attendance and educational attainment is evident, multivariate analysis
      controlling for urban/rural residence, region, parents' education, household
      wealth, and child's age, reveals that much of this association, especially that
      predicting educational attainment, is attributable to these other influences.
      Moreover, much of the effect that remains after statistical adjustment for the
      other influences is seen mainly at the largest family sizes. We consider the
      implications of these findings for current population policy in Vietnam and the
      possible features of the Vietnamese context that might account for the modest
      association.

PMID- 9512911
TI  - Maternal education and child health: is there a strong causal relationship?
AB  - Using data from the first round of Demographic and Health Surveys for 22
      developing countries, we examine the effect of maternal education on three
      markers of child health: infant mortality, children's height-for-age, and
      immunization status. In contrast to other studies, we argue that although there
      is a strong correlation between maternal education and markers of child health, a
      causal relationship is far from established. Education acts as a proxy for the
      socioeconomic status of the family and geographic area of residence. Introducing
      controls for husband's education and access to piped water and toilet attenuate
      the impact of maternal education on infant mortality and children's height-for
      age. This effect is further reduced by controlling for area of residence through
      the use of fixed-effects models. In the final model, maternal education has a
      statistically significant impact on infant mortality and height-for-age in only a
      handful of countries. In contrast, maternal education remains statistically
      significant for children's immunization status in about one-half of the countries
      even after individual-level and community-level controls are introduced.

PMID- 9512912
TI  - A dynamic analysis of turnover in employment and child care.
AB  - The causes of turnover in child-care arrangements and maternal employment are
      analyzed using panel data from the National Longitudinal Survey of Youth,
      supplemented with state-level information on child-care markets. The results
      indicate that turnover in child care is quite high and that child and family
      characteristics help explain turnover. Important factors include the mother's
      wage, the cost of child care, age of the child, and previous child-care
      decisions. The reduced-form nature of the analysis makes it difficult to
      determine whether these factors are important because they are associated with
      unstable child-care supply or because they affect family decisions, conditional
      on supply factors. The results provide no direct evidence that child-care
      turnover is higher in states with more unstable child-care markets.

PMID- 9512913
TI  - Economic and cultural influences on the decision to leave home in Peninsular
      Malaysia.
AB  - Although the departure of children from the parental home is an important life
      cycle event, few studies have investigated nest-leaving in developing countries.
      Using retrospective data from the Second Malaysian Family Life Survey, we
      estimate hazard models of nest-leaving in Peninsular Malaysia. We find that the
      departure of children, especially sons, responds to economic incentives,
      including housing costs, family businesses, education, and economic growth, and
      that ethnic differences in nest-leaving are important. We also find that the
      median age of departure from home has declined sharply over the past 40 years, a
      period of rapid social and economic change in Malaysia.

PMID- 9512914
TI  - Intergenerational relations in urban China: proximity, contact, and help to
      parents.
AB  - Although most older Chinese parents live with an adult son or daughter, most
      adult offspring do not live with parents. We examine the relations of these
      noncoresident offspring with parents in terms of proximity, frequency of contact,
      and exchange of help. Based on a 1993 random sample survey conducted in two major
      Chinese cities, we find that although rates of coresidence are high,
      noncoresident sons and daughters live close to parents, have frequent contact
      with their parents, and provide regular help to parents. Relationships with
      noncoresident sons and daughters are unaffected by whether parents coreside with
      another child. There is some evidence of closer relationships with sons than with
      daughters, but parents without a son receive as much help from all children as do
      parents with sons. The effects of these and other predictors are estimated in
      multivariate analyses, and results are interpreted in terms of the persistence or
      change of traditional family norms.

PMID- 9512915
TI  - Trends in single mothers' living arrangements from 1970 to 1995: correcting the
      current population survey.
AB  - I examine trends in single mothers' living arrangements using data from the 1970
      1995 Current Population Surveys. I create a consistent trend by correcting a
      coding problem that stemmed from the misidentification of children living in
      multigenerational households before 1984. Revised estimates show that the number
      of single mothers in each of these years was undercounted by 200,000-300,000. All
      of these women were subfamily heads living with their parents, and the problem
      occurred disproportionately among teens and black women. The uncorrected trend
      falsely indicates a large increase in the share of single mothers living with
      their parents. In reality, there was little change in the percentage of single
      mothers living in this arrangement over the time period. However, the data
      indicate a large increase in the rate of cohabitation and a comparable decline in
      the rate of living independently among this population.

PMID- 9512918
TI  - Recent epidemiological studies of the association between hormone replacement
      therapy and venous thromboembolism. A review.
AB  - The association between use of hormone replacement therapy (HRT) and the risk of
      venous thromboembolism (VTE) has been assessed in relatively few epidemiological
      studies. Evidence from the earliest studies did not support an increased risk of
      VTE among HRT users. However, methodological limitations in most studies,
      including small sample size and inadequate control of confounding, did not allow
      firm conclusions to be made. Most of these limitations have been overcome in 5
      recent studies which consistently show that the risk of VTE among women currently
      using HRT is 2 to 3 times higher than among women not using HRT. The overall
      relative risk of VTE for women currently using HRT obtained from these studies
      was 2.6 (95% confidence interval 1.6 to 4.2). This association is unlikely to be
      explained by confounding or other potential biases affecting observational
      studies. The risk appears to be more prominent during the first year of HRT use,
      and in 2 studies the risk disappeared after the first year of therapy. A dose
      response relationship, with a doubling of risk among users of high doses of
      estrogens, was shown in 2 of these studies. No major differences were observed
      with the different types of therapy, but users of unopposed estrogen therapy and
      transdermal therapy might be at lower risk than users of opposed regimens and
      oral preparations. Evidence from these new studies indicates that, among healthy
      post-menopausal women, between 1 and 2 additional cases of VTE per 10,000 women
      can be annually attributed to current use of HRT. The Committee on Safety of
      Medicines in the UK evaluated this risk as small and considered that it does not
      change the overall benefit-risk profile of HRT for most women.

PMID- 9512916
TI  - Systemic antifungal agents. Drug interactions of clinical significance.
AB  - There are 3 main classes of systemic antifungals: the polyene macrolides (e.g.
      amphotericin B), the azoles (e.g. the imidazoles ketoconazole and miconazole and
      the triazoles itraconazole and fluconazole) and the allylamines (e.g.
      terbinafine). Other systemic antifungals include griseofulvin and flucytosine.
      Most drug-drug interactions involving systemic antifungals have negative
      consequences. The interactions of amphotericin B, flucytosine, griseofulvin,
      terbinafine and azole antifungals can be divided into the following categories:
      (i) additive dangerous interactions; (ii) modifications of antifungal kinetics by
      other drugs; and (iii) modifications of the kinetics of other drugs by
      antifungals. Amphotericin B and flucytosine mainly interact with other agents
      pharmacodynamically. Clinically important drug interactions with amphotericin B
      cause nephrotoxicity, hypokalaemia and blood dyscrasias. The most important drug
      interaction of flucytosine occurs with myelotoxic agents. Hypokalaemia can
      precipitate the long QT syndrome, as well as potentially lethal ventricular
      arrhythmias like torsade de pointes. Synergism is likely to occur when either QT
      interval-modifying drugs (e.g. terfenadine and astemizole) and drugs that induce
      hypokalaemia (e.g. amphotericin B) are coadministered. Induction and inhibition
      of cytochrome P450 enzymes at hepatic and extrahepatic sites are the mechanisms
      that underlie the most serious pharmacokinetic drug interactions of the azole
      antifungals. These agents have been shown to notably decrease the catabolism of
      numerous drugs: histamine H1 receptor antagonists, warfarin, cyclosporin,
      tacrolimus, digoxin, felodipine, lovastatin, midazolam, triazolam,
      methylprednisolone, glibenclamide (glyburide), phenytoin, rifabutin, ritonavir,
      saquinavir, nevirapine and nortriptyline. Non-antifungal drugs like
      carbamazepine, phenobarbital (phenobarbitone), phenytoin and rifampicin
      (rifampin) can induce the metabolism of azole antifungals. The bioavailability of
      ketoconazole and itraconazole is also reduced by drugs that increase gastric pH,
      such as H2 receptor antagonists, proton pump inhibitors, sucralfate and
      didanosine. Griseofulvin is an enzymatic inducer of coumarin-like drugs and
      estrogens, whereas terbinafine seems to have a low potential for drug
      interactions. Despite important advances in our understanding of the mechanisms
      underlying pharmacokinetic drug interactions during the 1990s, at this time they
      still remain difficult to predict in terms of magnitude in individual patients.
      This is because of the large interindividual and intraindividual variations in
      the catalytic activity of those metabolising enzymes that can either be induced
      or inhibited by various drugs. Notwithstanding these variations, increasing
      clinical experience is allowing pharmacokinetic interactions to be used to
      advantage in order to improve the tolerability of some drugs, as recently
      exemplified by the use of a fixed combination of ketoconazole and cyclosporin.

PMID- 9512917
TI  - Adverse effects of neuromuscular blockers and their antagonists.
AB  - Among all the drugs used for general anaesthesia, neuromuscular blockers appear
      to play a prominent role in the incidence of severe adverse reactions. It now
      seems likely that most serious adverse drug reactions occurring during
      anaesthesia are immunological in type. The frequency of life-threatening
      anaphylactic or anaphylactoid reactions occurring during anaesthesia has been
      estimated to be between 1 in 1000 and 1 in 25,000 anaesthetic procedures, with
      the neuromuscular blockers being involved in 80% of cases. The mortality from
      such serious reactions is reported to be in the range of 3.4 to 6%. The highly
      immunogenic drug, suxamethonium chloride (succinylcholine), was found to be the
      most hazardous agent. Drug-specific immunoglobulin E antibodies to suxamethonium
      chloride and other neuromuscular blockers have been demonstrated. This
      sensitivity to neuromuscular blockers seems to be a long-lasting phenomenon.
      During anaesthesia, the clinical features of an allergic reaction are often
      masked. Tachycardia and circulatory collapse may be the only signs of an allergic
      reaction, and they are easily misdiagnosed. Bronchospasm is reported to be
      present in about 40% of cases. Successful management of these patients includes
      stabilisation during the acute reaction and avoidance of future reactions. The
      latter is based on the identification of the causative drug and potentially cross
      reacting compounds. The use of suxamethonium chloride is associated with many
      other adverse effects, such as fasciculations, myalgia, potassium release,
      changes in the heart rate, increases in intragastric and intraocular pressures,
      and malignant hyperthermia. Because of the dangers of hyperkalaemic cardiac
      arrest after suxamethonium chloride administration in children with unrecognised
      muscular dystrophy, there have now been moves to limit the use of this drug in
      children. Although neuromuscular blockers are designed to specifically block
      nicotinic cholinergic receptors at the neuromuscular junction, many bind to
      muscarinic cholinergic receptors on ganglia and smooth muscle, and alter
      parasympathetically mediated heart rate and airway calibre. Most
      benzylisoquinolinium muscle relaxants can induce histamine release, especially
      when they are administered rapidly, which can lead to disturbances of
      cardiovascular function. In addition, nondepolarising neuromuscular blockers have
      been implicated in causing generalised weakness following their long term
      administration to patients on an intensive care unit. The problem with these
      adverse drug reactions is their unpredictable nature. Therefore, prompt
      recognition with appropriate therapy can help to improve the outcome.

PMID- 9512919
TI  - Selecting an antidepressant for use in a patient with epilepsy. Safety
      considerations.
AB  - Depression is a common and disabling condition and is especially disabling for
      patients who also have epilepsy. Antidepressants, particularly the tricyclic
      antidepressants are well known to be associated with seizure activity, but this
      is a very neglected area of research. Most of the data on the proconvulsive
      effects of antidepressants come from either work in animal models or from
      research into the effects of antidepressants in overdose. Both of these
      situations may tell us little about the behaviour of antidepressants in patients
      with epilepsy. The selective serotonin [5-hydroxytryptamine; 5-HT] reuptake
      inhibitors have a low seizure propensity, are well tolerated in overdose and have
      a favourable adverse effect profile, making them suitable as first line
      treatments for depression in patients with epilepsy. Other antidepressants, e.g.
      trazodone, moclobemide, mirtazepine, are also likely to have minimal
      proconvulsive effects, but adverse effects, interactions with other drugs,
      especially anticonvulsants, or the lack of clinical data may make their use less
      attractive. Although this review has focused on these clinically important issues
      it is clear that considerably more research needs to be undertaken on the seizure
      propensity and clinical efficacy of antidepressants in patients with epilepsy.

PMID- 9512920
TI  - Treating breast cancer during pregnancy. What can be taken safely?
AB  - The occurrence of breast cancer during pregnancy is a rare clinical situation.
      However, if it is diagnosed, a multidisciplinary approach involving an
      obstetrician, a medical oncologist and a surgeon is needed. In this situation,
      breast cancer should be treated according to the same principles applied in
      nonpregnant patients. Termination of pregnancy does not improve survival.
      Decisions regarding abortion should be based on the desires of the patient and on
      therapeutic necessities. If required, surgery is always possible, but radiation
      therapy should be avoided because of the risk of fetal toxicity. Antineoplastic
      drug therapy, if indicated, is possible after the first trimester.

PMID- 9512922
TI  - Ab initio molecular modeling in the study of drug metabolism.
AB  - We discuss the use of ab initio quantum mechanical methods in drug metabolism
      studies. These methods require only the positions and atomic numbers of the atoms
      to be specified and offer greater transferability than conventional molecular
      modeling techniques. This fact, coupled with the accuracy of our approach,
      permits 'computational experiments' to be performed, allowing details of reaction
      mechanisms to be understood. We review the application of these methods to the
      cytochrome P450 superfamily of enzymes. There is much interest in understanding
      the mechanisms of these enzymes due to their participation in a wide range of
      metabolic processes including drug activation/deactivation. We find that our
      methods accurately reproduce the low- to high-spin transition of the haem Fe on
      binding of a substrate. Furthermore, we identify a new mechanism for the
      suppression of this spin transition, namely the shortening of the bond between
      the Fe atom and the coordinated S atom of the cysteine axial ligand. These
      results indicate that ab initio molecular modeling may be usefully applied in the
      study of drug metabolism and that further study of intermediate states in the
      P450 reaction cycle would be beneficial, particularly those which are not
      accessible using conventional experimental approaches.

PMID- 9512921
TI  - Treating recurrent affective disorders during and after pregnancy. What can be
      taken safely?
AB  - Since pregnancy and the time thereafter is a precarious period for women with
      recurrent affective disorders and their offspring, it is important to determine
      the risk of various treatments for such disorders. This review assesses the risk
      to the fetus, the perinatal risks for mother and infant, the risks associated
      with treatment during the puerperium and breastfeeding, and the risks to the
      later development of the child. This review considers treatment with lithium,
      tricyclic antidepressants (TCAs), selective serotonin (5-hydroxytryptamine; 5-HT)
      reuptake inhibitors (SSRIs), monoamine oxidase inhibitors, other antidepressants,
      and the anticonvulsants carbamazepine and valproic acid (sodium valproate).
      According to available evidence, use of lithium, TCAs and SSRIs is justified
      during and after pregnancy if treatment is required; no prophylactic treatment
      has a lower risk: benefit ratio. The review provides guidelines for the use of
      these drugs.

PMID- 9512923
TI  - Synthetic strategies to lower affinity for CYP2D6.
AB  - There are several models for the CYP2D6 active site with the characteristics of
      their substrates and inhibitors well defined. Imipramine possesses such
      characteristics and is both a substrate and an inhibitor of the CYP2D6 enzyme.
      Possible synthetic strategies to avoid interaction with the enzyme have been
      investigated, including: attenuation of basicity; and alteration of rigidity and
      length of the alkyl chain. Imipramine inhibited the 1'-hydroxylation of bufuralol
      (10 microM), an in vitro marker of CYP2D6 activity, in a CYP2D6 cell line (IC50 =
      2.4 microM). Inhibitory potency was attenuated by the removal of the basic
      centre; imipramine N-oxide had no inhibitory effect on bufuralol 1'
      hydroxylation. However, removal of this basic centre, as a strategy to decrease
      CYP2D6 interaction, may well have a detrimental effect on pharmacological
      efficacy. Both an increase and decrease in the N-N carbon chain length [2C,4C]
      caused a reduction in inhibitory potency. In addition, introduction of a carbonyl
      adjacent to the amino dibenzyl moiety into 2C, 3C and 4C compounds brought about
      a further reduction in inhibitory potency. These data demonstrate that changes to
      the molecule, distal to the basic centre, can attenuate the affinity of the
      molecule for CYP2D6 and are in keeping with the known characteristics of the
      enzyme.

PMID- 9512925
TI  - Cytochrome P450 dependent xenobiotic activation by physiological hydroperoxides
      in intact hepatocytes.
AB  - Xenobiotic metabolic activation by intact hepatocytes was recently shown to be
      enhanced by the addition of nontoxic concentrations of t-butyl hydroperoxide and
      prevented by cytochrome P450 inhibitors. Furthermore, H2O2 (Km = 103 microM) was
      found to be highly effective in supporting the human microsomal CYP1A2 catalyzed
      metabolic activation of the heterocyclic aromatic amine 2-amino-3-methylimidazo
      (4,5-f) quinoline (IQ) to mutagenic metabolites and the DNA adduct formed was the
      same as that formed by the mixed-function oxidase catalyzed activation system. In
      the following, it is shown that the cytotoxicity of other xenobiotics including
      carcinogenic arylamines and their N-hydroxyarylamine metabolites were markedly
      enhanced by hydroperoxide addition but not in the presence of cytochrome P450
      inhibitors. The CYP1A2 dependent O-demethylation of methoxyresorufin in 3
      methylcholanthrene induced hepatocytes was also markedly enhanced when
      intracellular H2O2 was generated by the mitochondrial monoamine oxidase (MAO)
      substrates tyramine or kynurenamine. Linoleic acid hydroperoxide also
      dramatically enhanced the cytotoxicity of phenelzine towards isolated hepatocytes
      and the microsomal metabolism of phenelzine to form ethylbenzene. The P450
      inhibitors phenylimidazole, benzylimidazole prevented the metabolic activation of
      phenelzine but not lipid peroxidation. These results suggest that linoleic acid
      hydroperoxide can activate hydrazines via a cytochrome P450 peroxidase catalyzed
      one electron oxidation to form highly cytotoxic reactive intermediates.
      Furthermore, increased hydrogen peroxide formation, e.g. as a result of oxidative
      stress, would also be expected to enhance the metabolic activation of
      carcinogenic arylamines via the peroxygenase function of CYP1A2.

PMID- 9512924
TI  - Comparison of CYP2A6 catalytic activity on coumarin 7-hydroxylation in human and
      monkey liver microsomes.
AB  - Comparison of 7-hydroxylation of coumarin, a CYP2A6 substrate, in human and
      African green and cynomolgus monkey liver microsomes was made by means of an HPLC
      assay with UV detection. In human liver microsomes, the Km and Vmax values for
      the metabolic conversion were 2.1 microM and 0.79 nmol/mg/min, respectively.
      While African green monkey showed Km and Vmax values of 2.7 microM and 0.52
      nmol/mg/min, which were similar to human, higher Km and Vmax values were found in
      cynomolgus monkey. Coumarin 7-hydroxylation in human and African green monkey was
      selectively inhibited by methoxsalen and pilocarpine (CYP2A6 inhibitors) but not
      by other inhibitors, i.e. alpha-naphthoflavone (CYP1A1), orphenadrine (CYP2B6),
      sulfaphenazole (CYP2C9), quinidine (CYP2D6) and ketoconazole (CYP3A4).
      Immunoinhibition results supported CYP2A6 involvement in human and its homolog in
      monkey in coumarin 7-hydroxylation, as only anti-CYP2A6, but not CYP2B1, CYP2C13,
      CYP2D6, CYP2E1 or CYP3A antibodies, inhibited this conversion. African green
      monkey was found to be similar to human in catalytic activity of coumarin 7
      hydroxylation and response to CYP2A6 inhibitors or antibody inhibition. However,
      the monkey CYP2A6 is not identical to the human in that Ki values were different,
      and differences were observed with some CYP2A6 inhibitors, such as nicotine and
      methoxsalen, suggesting that, under some circumstances, studies of nicotine
      kinetics and drug taking behavior in monkey may not be comparable to human.

PMID- 9512926
TI  - Development of an in vitro reporter gene assay to assess xenobiotic induction of
      the human CYP3A4 gene.
AB  - The current work concerns the development and validation of an in vitro reporter
      gene assay system for the assessment of induction of human CYP3A4. A plasmid
      containing approximately 1 kb of the CYP3A4 regulatory region (which contains
      several recognised regulatory elements including glucocorticoid responsive
      elements) coupled to the reporter gene for human secreted placental alkaline
      phosphatase (SPAP) was transfected into the human hepatoblastoma cell line HepG2.
      Calcium phosphate precipitation was the method of choice for transfection. The
      transfected cells were dosed with known inducers of CYP3A4 and the levels of SPAP
      in the medium were subsequently measured using a chemiluminescent assay, as an
      indirect measure of CYP3A4 induction. The inducers used in this study included
      dexamethasone, phenytoin, triacetyloleandomycin (TAO), rifampicin, carbamazepine,
      phenylbutazone and sulfinpyrazone. These compounds activated CYP3A4 by between
      1.5-4.5-fold thus representing a major advance in assessing the induction of
      human CYP genes in vitro.

PMID- 9512927
TI  - CYP4A1 gene transfection studies and the peroxisome proliferator-activated
      receptor: development of a high-throughput assay to detect peroxisome
      proliferators.
AB  - An in vitro reporter gene assay has been established to examine cytochrome
      P4504A1 (CYP4A1) induction. A response element from the upstream region of the
      rat CYP4A1 gene containing a peroxisome proliferator response element (PPRE) has
      been linked to the chloramphenicol acetyl-transferase (CAT) gene in a reporter
      vector (1). This CYP4A1 reporter construct has been co-transfected into human
      HepG2 cells in the presence and absence of expression vectors encoding the
      transcription factors PPAR alpha and RXR alpha. The assay employs calcium
      phosphate-DNA co-precipitate mediated transfection. Reporter gene products have
      been quantitated using chemiluminescent based assays. We have shown that, in the
      presence of PPAR alpha, the above CYP4A1 construct is transcriptionally activated
      by a range of structurally different peroxisome proliferators including Wy
      14,643, ciprofibrate, clofibric acid and nafenopin. Our future efforts will focus
      on the establishment of a high-throughput assay for the detection of peroxisome
      proliferators. Such an assay would provide an invaluable in vitro test for the
      screening of developmental drug candidates prior to in vivo studies.

PMID- 9512929
TI  - An epitope-tagging system for studying regulation of the peroxisome proliferator
      activated receptor alpha (PPAR alpha).
AB  - Peroxisome proliferators (PPs) are a group of compounds which cause peroxisome
      proliferation and hepatocellular carcinomas in rodents, and form a class of non
      genotoxic carcinogens. It is thought that PPs act via a receptor similar to
      members of the nuclear hormone superfamily termed the peroxisome proliferator
      activated receptor (PPAR). Multiple subtypes (alpha, beta, delta and gamma) of
      the receptor exist and are differentially expressed between tissues and species.
      PPAR alpha has been shown to activate transcription by binding to response
      elements upstream of peroxisome proliferator responsive genes. However, despite
      the isolation of transcriptionally active human subtypes of the receptor, hPPAR
      alpha and hNUC1, humans are thought to be non-responsive to PPs. This is possibly
      due to regulation of PPAR, and it has been recently reported that PPAR alpha is a
      phosphoprotein in vivo and insulin regulates its phosphorylation. A system
      employing epitope-tagged receptors has been developed to study this further, with
      the aim of establishing stably transfected cell lines expressing high levels of
      epitope-tagged mouse and human PPAR alpha. Our experiments clearly demonstrate
      that an epitope-tagged mPPAR alpha receptor has an equal ability to modulate
      transcription as the native receptor in transactivation assays and will be
      further used to examine the molecular mechanisms of peroxisome proliferation.

PMID- 9512928
TI  - Use of competitive RT-PCR in the molecular analysis of peroxisome proliferation.
AB  - The technique of quantitative competitive RT-PCR to determine the levels of mRNA
      expression of genes encoding peroxisome proliferator-activated receptor alpha
      (PPAR alpha), acyl coenzyme-A (ACOX) and cytochrome P450 4A1 (CYP4A1) in primary
      rat hepatocyte cultures is described. This technique is based on the co
      amplification of an internal standard (PCR MIMIC) and target DNA sequence with
      one set of primers. Following total RNA extraction and reverse transcription,
      competitive PCR was carried out by mixing various dilutions of known
      concentrations of PCR MIMIC with constant amounts of cDNA. Densitometry was then
      carried out on the DNA bands obtained following gel electrophoresis and, after
      correcting for size differences between the target DNA and MIMIC, the
      concentration of target DNA was calculated and expressed as attomoles (10-18
      moles) per microgram total RNA. Constitutive levels of PPAR alpha, ACOX and
      CYP4A1 obtained were 0.037 +/- 0.003, 1.858 +/- 0.470m and 0.035 +/- 0.007
      attomoles/microgram RNA, respectively. Following 24 h culture of rat primary
      hepatocytes in the presence of sodium clofibrate (a peroxisome proliferator), the
      levels of PPAR alpha, ACOX and CYP4A1 were increased by 2.1-, 3.3- and 12.8-fold,
      respectively. Thus the technique described in this study has high sensitivity and
      can be used to accurately measure the mRNA steady state levels in cell cultures.

PMID- 9512930
TI  - Molecular profiling of non-genotoxic hepatocarcinogenesis using differential
      display reverse transcription-polymerase chain reaction (ddRT-PCR).
AB  - The technique of differential display reverse transcription-polymerase chain
      reaction (ddRT-PCR) has been used to produce unique profiles of up-regulated and
      down-regulated gene expression in the liver of male Wistar rats following short
      term exposure to the non-genotoxic hepatocarcinogens, phenobarbital and WY
      14,643. Animals were treated for 3 days, whereupon their livers were extracted
      and snap frozen. mRNA was prepared from the livers and used for ddRT-PCR.
      Individual bands from the differential displays were extracted and cloned. False
      positives were eliminated by dotblot screening and true positives then sequenced
      and identified.

PMID- 9512931
TI  - Developmental modulation of cysteine conjugate beta-lyase/glutamine transaminase
      K/kynurenine aminotransferase mRNA in rat brain.
AB  - Cysteine conjugate beta-lyase/glutamine transaminase K/kynurenine
      aminotransferase (CS-lyase/GTK/KAT) is a tri-functional enzyme found in several
      organs, including the brain. Kynurenine aminotransferase is important in
      tryptophan metabolism in the CNS, producing kynurenic acid, a NMDA receptor
      antagonist and neuroprotective. Tryptophan not metabolised via kynurenine
      aminotransferase may form quinolinic acid, a NMDA receptor agonist and
      neurotoxin. Kynurenic acid co-treatment blocks quinolinic acid induced lesions in
      the CNS in rat. In many conditions exhibiting neurodegeneration (i.e.
      Huntington's, Parkinsonism, Down's syndrome) quinolinic acid and/or kynurenic
      acid concentrations are altered, suggesting the ratio of these chemicals may be
      important in neurodegeneration. We have investigated the developmental modulation
      of CS-lyase/GTK/KAT mRNA in rat brain. CS-lyase/GTK/KAT mRNA was measured in 14,
      21, 28, 35, 42 day post-natal and adult rats. While many regions demonstrated a
      steady increase to adult levels, two other profiles were seen. Five regions
      rapidly reached adult levels of the mRNA, while two peaked above the adult level
      before falling back. This provides evidence that expression of the CS
      lyase/GTK/KAT gene is physiologically modulated, and provides the basis for
      further investigation into the mechanism of control. Artificial modulation could
      possibly be used to alter levels of the neuroprotectant kynurenic acid in
      neurodegeneration.

PMID- 9512932
TI  - Comutagenesis--V: rapid conversion of 2-hydroxyl-amino-3-methylpyridineto 2-amino
      3-methylpyridine by a hepatic S9 preparation.
AB  - The in vitro metabolism of 2-hydroxylamino-3-methylpyridine has been investigated
      using arochlor 1254 pretreated rat S9 mixtures. 2-Hydroxylamino-3-methylpyridine
      is rapidly converted to the parent amine 2-amino-3-methylpyridine. No further
      oxidation products of 2-hydroxylamino-3-methylpyridine (i.e. nitroso or nitro)
      were detected under the HPLC conditions used. This observation may explain our
      previous findings on the in vitro metabolism of 2-amino-3-methylpyridine where no
      hydroxylamino metabolite was detected.

PMID- 9512933
TI  - In vitro metabolic N- and C-oxidation of phenanthridine.
AB  - The in vitro microsomal metabolism of phenanthridine has been studied to
      establish as to whether phenanthridine produces the corresponding N-oxide and
      lactam as metabolites and the mechanism involved. We now report our preliminary
      findings using rat hepatic microsomal preparations (control and induced with
      phenobarbitone) fortified with NADPH. The potential metabolite, phenanthridine-N
      oxide, was prepared by m-CPBA oxidation of substrate; the lactam was commercially
      available. The substrate and metabolites were extracted and analysed by HPLC and
      TLC. Five metabolites, i.e. the corresponding N-oxide, lactam and three other
      products, were detected. Both N-oxide and lactam metabolites showed identical
      chromatographic behaviour and UV spectrum--using a multi-array UV detector linked
      to a HPLC system--as the authentic compounds. The uncharacterised metabolites are
      proposed to be phenolic because of their chromatographic behaviour and response
      to detection reagents. The amount of N-oxide and lactam formed was significantly
      increased when phenobarbitone induced rat microsomes were used as enzyme source.
      The results indicate that these latter metabolites are probably formed by a
      phenobarbitone inducible CYP450 isozyme. It may be that the lactam was produced
      via the N-oxide and experiments are under way to investigate the proposed
      pathway.

PMID- 9512934
TI  - In vitro microsomal metabolism of nuclear chloro substituted secondary amines and
      imines.
AB  - The metabolism of N-(4-chlorobenzyl)-4-chloroaniline (CBCA), N-(4-chlorobenzyl)-4
      chlorobenzylamine (CBCBA), and N-(4-chlorobenzylidene)-4-chlorobenzylamine
      (CBDCBA) were studied in vitro using rat liver microsomal preparations. The
      secondary amines produced the corresponding N-oxidation products (hydroxylamines
      and nitrones) and dealkylation products (4-chlorobenzaldehyde and primary
      amines). Both secondary amines failed to produce the corresponding amides, whilst
      the parent imine was detected as a metabonate. CBDCBA, the intermediate imine of
      CBCBA metabolism, was also incubated under similar conditions. However, no
      oxaziridine was detected.

PMID- 9512935
TI  - In vitro metabolism of GV150013X by using liver microsomes and liver tissue
      slices from different species.
AB  - The metabolism of GV150013X was studied in vitro using washed liver microsomes
      and liver tissue slices from different species. This work was carried out in
      order to compare the metabolite profiles resulting from incubation of GV150013X
      with human, rat, dog and rabbit liver microsomes and those from rat, rabbit and
      human liver tissue slices. This compound was found to be converted to at least 8
      metabolites by rat and human liver microsomes. In rabbit liver microsomes, the
      three metabolites M4, M7 and M8, and in dog liver microsomes metabolite M1, were
      not detected. The main metabolites, M2, M5 and M6, were present in human, rat and
      rabbit liver tissue slices, while the three metabolites M3, M4 and M8 and
      metabolite M1 were not detected in rabbit and rat liver tissue slices,
      respectively. In rat liver tissue slices, the major metabolites plus five minor
      metabolites, one sulphate conjugate of a monohydroxylated, three trihydroxylated
      and one dihydroxylated were identified based on HPLC retention time and
      thermospray-mass spectrometry data. Quantitative species differences among rat,
      dog, rabbit and human were observed, while qualitative differences only between
      rabbit and other species were detected.

PMID- 9512936
TI  - Metabolism of 9-(2-chlorobenzyl)-, 9-(2-methylbenzyl)- and 9-(2-methoxybenzyl)
      adenines by hamster hepatic microsomes.
AB  - It was previously found that 9-benzyladenine (BA) was extensively N1-oxidised by
      animal hepatic microsomes; further, mononitrosubstitution in the phenyl moiety of
      BA significantly modified the N1-oxidation rates of the corresponding substrates.
      In order to establish whether the electronic nature or a steric effect of the
      substituents in the phenyl moiety is the reason for the modification of N1
      oxidation rate, the metabolism of some 2'-substituted 9-benzyladenines, i.e. 9-(2
      chlorobenzyl)adenine (2CBA), 9-(2-methyl-benzyl)adenine (2MBA) and 9-(2
      methoxybenzyl)adenine (2MOBA), by hamster hepatic microsomes was studied. It was
      found that the N1-oxide was still the major metabolite for 2CBA. However, only
      minor amounts of N1-oxides were formed during microsomal incubation with 2MBA and
      2MOBA. On the other hand, in spite of the higher N1-oxidation rate of 2CBA, its
      total biotransformation rate was slightly lower than the other two substrates.
      Like other 9-aralkyladenines previously studied, dealkylation occurred for all
      three substrates. It was also found that another two metabolites formed in
      significant amounts in the incubates from both 2MBA and 2MOBA. These metabolites
      were not fully characterised and their structures unknown.

PMID- 9512937
TI  - Studies on the relationship between in vitro metabolism and certain
      physicochemical characteristics of some 9-alkyl-/9-aralkyl adenines.
AB  - Previous studies demonstrated that biological N1-oxidation occurred for some 9
      alkyl-/9-aralkyladenines, but not for others, when mammalian hepatic microsomal
      incubates were used as enzyme source. In order to understand the mechanisms
      controlling the metabolic fate of these compounds, the relationship between N1
      oxidation and certain physicochemical characteristics of these substrates was
      studied. It was found that there was no marked link between N1-oxidation and the
      computer predicted pKa values of the substances studied. However, a computer
      predicted LogP value in the range 1.3-4 seems to be the most favourable for N1
      oxidation. The 1H-NMR and 13C-NMR spectroscopic characteristics of the
      substrates, which reflect certain electronic characteristics of the purine
      moiety, also showed a correlation with their N1-oxidation. The electronic effects
      of the substrates in relation to their metabolism was investigated using computer
      modelling techniques; the results showed that different substituents at the 9
      position of adenine may modify the electronic characteristics of the purine
      moiety thus affecting their metabolism. The conformation of the substrates may
      also be an important controlling factor for their N1-oxidative metabolism.

PMID- 9512938
TI  - The in vitro metabolism of norcotinine and related biotransformation products by
      microsomal preparations.
AB  - Since norcotinine and 4-(3-pyridyl)-4-oxobutyramide (POBAM) are probable
      metabolites of nicotine and cotinine, it was of interest to investigate the
      further in vitro metabolism of these compounds. We now report our preliminary
      findings using rat microsomal preparations (induced and/or non-induced with
      phenobarbitone) fortified with NADPH. Following norcotinine metabolism, two
      compounds, i.e. the corresponding ketoamide (POBAM) and another product, were
      detected. The latter metabolite has an identical HPLC retention time as that of
      nicotinamide. Both metabolites showed identical UV spectra when compared to
      authentic compounds using a multi-array UV detector linked to a HPLC system. The
      structures of these metabolites were also confirmed by mass spectral analyses.
      The amount of POBAM was significantly increased when phenobarbitone induced rat
      microsomes was used. It indicates that the ketoamide is formed via a
      phenobarbitone inducible isozyme of CYP450. Following the metabolism of POBAM,
      two compounds, i.e. the corresponding acid (POBA) and an unidentified product,
      were detected. The uncharacterised compound had an identical HPLC retention time
      as nicotinamide. Both metabolites gave a UV spectrum identical to the authentic
      compounds. The detection of nicotinamide in incubates of norcotinine and POBAM
      suggests that it is released from NADP(H) by a stimulatory effect on
      glycohydrolase by the substrates. Further studies on the enzymology of these
      processes are in progress.

PMID- 9512939
TI  - Metabolism of (-)-(S)-nicotine by guinea pig and rat brain: identification of
      cotinine.
AB  - Since the brain is the major site of pharmacological activity of nicotine, it was
      of interest to investigate the metabolism of nicotine by this organ. We now
      report our findings using guinea pig and rat brain as the enzyme source. Whole
      brains were removed and washed with isotonic KCl, blotted dry and cut into small
      pieces. The tissue was weighed and homogenized in pH 7.4 Tris-KCl buffer, 2 ml/g
      tissue. Incubations were carried out using 0.5 ml of brain homogenate and 0.1-1
      mumol of nicotine at 37 degrees C. The reactions were terminated by freezing at 
      80 degrees C. The samples were extracted and analyzed by capillary GC with
      nitrogen-phosphorus detection. Cotinine was detected as the major metabolite and
      its identity confirmed by GC-MS. Cotinine formation may contribute to the
      detoxication pathway of nicotine and may be important in controlling nicotine
      levels in the brain. Furthermore, the conversion of nicotine to cotinine involves
      the intermediacy of nicotine-delta [1'(5')]-iminium ion, which is an alkylating
      agent. This finding supports the concept that reactive intermediates may play a
      role in the pharmacology and toxicology of nicotine.

PMID- 9512940
TI  - Metabolism of (-)-(S)-nicotine in the isolated perfused rabbit lung.
AB  - The metabolism of (-)-(S)-nicotine has been investigated following intratracheal
      administration to the recirculating perfused rabbit lung model. The metabolic
      products present in the perfusate were identified by co-chromatography (HPLC and
      GC) with authentic standards and quantified by HPLC. After the 180 min perfusion
      period, nicotine was found to be metabolically transformed to cotinine (33.7%), 3
      hydroxycotinine (10.4%), cotinine-1-N-oxide (3.4%) and nicotine-1'-N-oxide
      (14.4%). Norcotinine, nornicotine, 3-pyridyl-4-oxo-N-methylbutyramide and an
      uncharacterised metabolite were also detected in low amounts. Following the
      perfusion experiment, part of the lung tissue was homogenised in the presence of
      [14C]-sodium cyanide. Subsequent analysis of the homogenates indicated the
      formation of 2'-cyanonicotine, 1'-cyanomethylnornicotine and the
      diastereoisomeric 5'-cyanonicotines.

PMID- 9512941
TI  - Acetylation of arylamines by the placenta.
AB  - The N-acetylation of arylamines and hydrazines used as drugs may alter their
      pharmacological or toxicological activity. Arylamine N-acetyltransferase (NATs)
      are involved in drug metabolism, as they catalyse the N-acetylation of arylamine
      and mono-substituted hydrazine substrates. Placental metabolism regulates the
      nature of the chemicals which reach the developing fetus. The study of drug
      metabolism during pregnancy is important in determining the effect on the fetus
      of drugs administered to the mother and the maternal drug dose required,
      important if the treatment is to be effective. There are two forms of NAT in
      humans, NAT1 and NAT2, which are encoded at multi-allelic loci. There is inter
      individual variation in both NAT1 and NAT2 activity, which has implications in
      drug dosage. Using a combination of enzyme activity measurements and Western
      blotting, this study has characterised the arylamine N-acetylation capabilities
      of placenta and cord blood. NAT1 activity in placenta and cord blood demonstrated
      inter-individual variation and the variation was in the range expected for adult
      NAT1 activity. The genotypes of both NAT1* and NAT2* were determined using DNA
      prepared using placental blood clots (maternal DNA) and cord blood (fetal DNA).
      The results indicate that placental NAT activity is an important factor when
      considering N-acetylation during pregnancy.

PMID- 9512942
TI  - Stereoselective absorption and hydrolysis of cefuroxime axetil diastereomers
      using the Caco-2 cell monolayer model.
AB  - Cefuroxime axetil, the orally active prodrug of cefuroxime is marketed as a 1:1
      mixture of two diastereomers designated as R (1'R, 6R, 7R) and S (1'S, 6R, 7R).
      Prodrug hydrolysis is thought to occur during intestinal absorption, however
      little is known concerning the relative availability of cefuroxime from each
      isomeric form. The Caco-2 cell monolayer model was used to examine the possible
      stereoselectivity of absorption by measuring the accumulation and epithelial
      transport rate in the apical to basolateral direction of cefuroxime and
      cefuroxime axetil following application of the mixture (1.0 mM) or individual
      diastereomers (0.5 mM0 of cefuroxime axetil. Cefuroxime appearance in the
      basolateral chamber was in the order: mixture > R > S following application of
      the prodrug. The accumulation of unchanged cefuroxime axetil was S > R
      irrespective of the form applied, i.e. individual diastereomer or the mixture.
      Such stereoselective differences in both absorption and/or hydrolysis may
      contribute to the observed oral bioavailability (30-50%) of cefuroxime in vivo.

PMID- 9512943
TI  - A study on the route of 1-methylurate formation in theophylline metabolism.
AB  - The urinary excretion patterns of theophylline metabolites were studied in a
      subject on a routine, oral dose of 600 mg/day. The highest correlation was
      observed between the excretions of 1,3-dimethylurate and 1-methylurate (r = 0.73
      +/- 0.08). The poorest correlations were observed when the excretion of 1
      methylxanthine was compared to those of 1-methylurate and 1,3-dimethylurate (r <
      or = 0.55, P > or = 0.05). The difference in the quality of the correlations was
      not due to rate-limiting or class-specific carries. The results suggested that 1
      methylurate did not derive solely from 1-methylxanthine, implicating 1,3
      dimethylurate as an alternative source. When the theophylline regimen was
      supplemented by a single dose of caffeine (4.80 mg/kg), the recovery of unaltered
      caffeine and the yield of metabolites arising from the primary 3-demethylation of
      caffeine (1-methylxanthine, 7-methylxanthine, 1-methylurate, 1,7-dimethylxanthine
      and 1,7-dimethylurate) were found to be unchanged. The lack of competition
      between caffeine and theophylline indicated that caffeine 3-demethylation and the
      demethylations of theophylline are not catalyzed by the same cytochrome P450
      system.

PMID- 9512944
TI  - The determination of nandrolone and its metabolites in urine by gas
      chromatography-mass spectrometry.
AB  - The determination of nandrolone and its major metabolites in urine of a healthy
      volunteer is typically performed by fused-silica capillary column gas
      chromatography with electron impact quadropole mass spectrometry. Two well-known
      urinary metabolites of nandrolone, 19-norandrosterone and 19-norethiocholanolone,
      were isolated by XAD-2 adsorption from urine, eluted with methanol and separated
      into unconjugated and conjugated fractions. The conjugated fraction was
      hydrolyzed with beta-glucuronidase from Escherichia coli and the samples
      derivatized with MSTFA/ammonium iodide/dithioerythritol. Ion fragmentograms of
      the bis-trimethylsilyl derivatives of nandrolone and its metabolites displayed
      molecular ions of M+ = 420 and M(+) -15 = 405. Extraction yield and the minimum
      detection limit of nandrolone in urine were identified. Finally, excretion rates
      of nandrolone and its metabolites in urine were determined.

PMID- 9512945
TI  - An improved HPLC method for analysis of methamphetamine and its metabolites in
      plasma.
AB  - An improved HPLC method for analysis of methamphetamine (MAMP) and its
      metabolites in plasma was established, which features: high and reliable
      extraction recovery without loss of the analytes during solvent evaporation; no
      need for sample derivatization, and simultaneous analysis of MAMP, its N
      demethylation and 4-hydroxylation metabolites. The major modification on the
      previous extraction procedure is addition of HCl to ethyl acetate extract prior
      to evaporation, resulting in significant increases in recovery, reproducibility
      and sensitivity. HPLC analysis is performed with an isocratic system on a C6
      column. Samples are eluted with a mobile phase of acetonitrile-10 mM phosphate
      buffer containing 0.1% triethylamine (pH 6) at a flow rate of 1.0 ml/min, and
      monitored by a UV detector at a wavelength of 214 nm. All the analytes elute
      within 24 min. This method was successfully applied to the analysis of MAMP and
      its metabolites in rat plasma after MAMP dosing.

PMID- 9512946
TI  - Randomized comparative multicenter study of hydroxyethyl starch versus albumin as
      a plasma expander in cirrhotic patients with tense ascites treated with
      paracentesis.
AB  - OBJECTIVE: Large-volume paracentesis associated with plasma volume expansion with
      albumin is an effective, safe, but costly therapy for ascites in patients with
      cirrhosis. The aim of this study was to compare the use of a synthetic plasma
      expander, hydroxyethyl starch (HES), with that of albumin. DESIGN: Sixty
      cirrhotic patients with ascites were studied. Patients were randomly assigned to
      be infused with either albumin (8 g/l of ascites removed, n = 33) or HES (200
      ml/l of ascites removed, n = 27). None of the patients was treated with diuretics
      or had renal impairment or hyponatremia at entry. Clinical and laboratory data
      were obtained before and 1, 3 and 15 days after treatment. RESULTS: There were no
      significant differences in clinical and laboratory parameters between the two
      groups at entry into the study. None of the patients developed renal impairment
      during the trial. One patient (HES group) presented with hyponatremia. Plasma
      atrial natriuretic factor and aldosterone levels did not differ between the two
      groups at baseline or at 1 and 3 days after paracentesis. The volume of ascites
      removed did not differ between the albumin (7.9 +/- 4.4 l) and HES (6.9 +/- 5.3
      l) groups. However, there was a significant difference in weight loss between the
      albumin and HES groups (7.9 +/- 5.2 kg vs 4.7 +/- 3.4 kg; p = 0.01). Clinical and
      laboratory parameters indicated that HES was well tolerated except for
      hypoalbuminemia. CONCLUSION: HES is well tolerated in patients with cirrhosis.
      There is no difference between HES and albumin in the prevention of complications
      related to large-volume paracentesis. The lesser degree of weight loss observed
      with HES needs further study.

PMID- 9512947
TI  - Effect of dopamine on portal blood flow in cirrhotic patients.
AB  - OBJECTIVE: The effects of dopamine infusion on portal blood flow were examined in
      12 cirrhotic patients (seven men, five women) in a Child-B group. METHODS:
      Dopamine was administered as an intravenous infusion (2 micrograms kg-1 min-1).
      RESULTS: At 0, 30 and 60 min, portal blood flow, left ventricular systolic and
      diastolic functions were evaluated using the pulsed doppler method. No
      significant difference was found between heart rate, blood pressure and
      parameters demonstrating left ventricular systolic and diastolic functions before
      and after dopamine infusions. Portal blood flow decreased significantly at 30 and
      60 min. Portal blood flow fell from 1802 +/- 88 to 1339 +/- 50 ml min-1 (P <
      0.001) at 30 min and to 1121 +/- 60 ml min-1 (P < 0.001) at 60 min. CONCLUSION:
      The reducing effects of dopamine on portal blood flow in cirrhotic patients were
      demonstrated by the pulsed doppler method, which is a noninvasive test.

PMID- 9512948
TI  - Influence of the transmission route and disease duration in the histopathology of
      chronic hepatitis C: a study of 101 patients.
AB  - OBJECTIVE: Different studies have demonstrated that factors such as transmission
      route, disease duration and age at the time of infection can influence the
      histological evolution of chronic hepatitis by the hepatitis C virus (HCV). The
      aim of this study was to determine if epidemiological factors such as disease
      duration and transmission route influence the severity of the histological
      lesions of patients with chronic hepatitis by HCV. DESIGN: A prospective study.
      METHODS: The hepatic biopsies of 101 patients diagnosed with chronic hepatitis by
      HCV were studied. The patients were divided into three groups according to
      transmission mode: (1) post-transfusional (n = 28), (2) associated with the use
      of drugs by parenteral route or intravenous drug use (n = 28), and (3) sporadic
      hepatitis (n = 45). RESULTS: We found more severe forms of hepatopathy in post
      transfusional hepatitis and sporadic groups than in the intravenous drug user
      group of patients. The disease evolution time was significantly higher in
      patients diagnosed as having chronic active hepatitis with or without cirrhosis
      (13.8 +/- 9 years) than in patients with chronic persistent hepatitis (8 +/- 4
      years), P < 0.01. We found a significant correlation between the evolution time
      of the infection by HCV and the Histology Activity Index (P < 0.01). The
      multivariate analysis showed that only the transmission route and the disease
      evolution time are predictive variables of Histology Activity Index in chronic
      hepatitis C. CONCLUSION: These results suggest that the post-transfusional and
      sporadic transmission routes and a greater evolution time of the disease are
      epidemiological variables that are associated with the presence of more severe
      histological lesions in chronic hepatitis C.

PMID- 9512949
TI  - Prognostic factors in cirrhotic patients receiving long-term sclerotherapy for
      the first bleeding from oesophageal varices.
AB  - OBJECTIVE AND DESIGN: The aim of this study was to identify prognostic factors in
      cirrhotic patients receiving long-term sclerotherapy for their first bleeding
      from oesophageal varices. METHODS: Ninety-eight patients with acute bleeding from
      oesophageal varices receiving long-term endoscopic injection sclerotherapy were
      retrospectively investigated. Thirteen variables (five qualitative and eight
      quantitative) related to clinical, biological, and radiographic features were
      collected at admission. The qualitative variables were: gender, hepatocellular
      carcinoma, cause of cirrhosis, ascites and degree of encephalopathy. The
      quantitative variables were age, bilirubin, albumin, prothrombin index, number of
      sessions of sclerotherapy, volume of ethanolamine oleate, time taken to reach the
      hospital and shock index. These variables were examined with a multivariate
      analysis using stepwise logistic regression procedures and a prognostic index was
      calculated from the Cox equation. The predictive power of the final Cox model was
      prospectively tested in 43 patients with cirrhosis receiving long-term
      sclerotherapy for their first variceal bleeding. RESULTS: Of the 13 variables
      studied in a multivariate analysis using a logistic regression model, four had an
      independent prognostic value: the presence of hepatocellular carcinoma,
      bilirubin, albumin and time taken to reach the hospital. When the Cox model was
      examined in an independent set of 43 patients, there were no statistically
      significant differences between the observed and expected survival. CONCLUSION:
      Prognosis of patients with bleeding from oesophageal varices is related to
      residual liver function and time taken to reach the hospital. Furthermore, the
      presence of hepatocellular carcinoma is an additional risk factor.

PMID- 9512950
TI  - Screening for drug related dyspepsia: an analysis of prescription symmetry.
AB  - OBJECTIVE: Most patients with severe upper dyspepsia are treated empirically with
      ulcer drugs. Drug-induced dyspepsia might therefore be reflected in the
      sequencing of ulcer drugs relative to other medications. Our aim was to screen a
      large population-base prescription database for evidence of drug-induced
      dyspepsia. METHODS: Prescription data on 31,232 incident users of ulcer drugs
      were drawn from a research database, covering the county of Funen, Denmark. We
      identified all individuals who had started their first recorded therapies with an
      ulcer drug and another non-ulcer drug within a 100 day span. In this selected
      group, there would normally be an equal number starting either drug first, while
      a dyspepsia-provoking effect of the non-ulcer drug would manifest as an excess of
      individuals with the ulcer drug prescribed last. This screening method is robust
      to confounders that are stable over time. RESULTS: Only non-steroidal
      antiinflammatory drugs (adjusted rate ratio (RR) 1.8, 95% confidence interval
      (CI), 1.6-2.0), calcium blockers (RR 1.4, CI 1.2-1.7), corticosteroids (RR 1.1,
      CI 1.0-1.3), angiotensin converting enzyme inhibitors (RR 1.4, CI 1.1-1.7) and
      methylxanthines (RR 1.5, CI 1.1-2.2) showed a significant asymmetry suggesting a
      dyspepsia-provoking effect. An analysis of effect modifiers suggested that the
      signals for corticosteroids and for angiotensin converting enzyme inhibitors were
      explained by concurrent use of non-steroidal anti-inflammatory drugs and by
      underlying congestive heart failure. The signal for non-steroidal anti
      inflammatory drugs may be explained by the known reputation of non-steroidal
      antiinflammatory drugs for causing ulcers. CONCLUSION: There are hardly any
      important unknown drug effects that mimic acid related dyspepsia. Drug-induced
      dyspepsia contributes little to the overall use of ulcer drugs.

PMID- 9512951
TI  - Intestinal absorption of oestrogen: the effect of altering transit-time.
AB  - OBJECTIVE: The mechanism by which a high fibre diet may reduce serum oestrogens
      is unknown. We hypothesized that time is a rate-limiting factor in oestrogen
      absorption from the colon so that changes in colonic transit-rate affect the
      proportion of oestrogen that is deconjugated and/or absorbed. AIM: To determine
      if alteration of intestinal transit rate would influence the absorption of an
      oral dose of oestradiol glucuronide. PARTICIPANTS: Twenty healthy postmenopausal
      women recruited by advertisement. SETTING: Department of Medicine, Bristol Royal
      Infirmary. METHODS: Volunteers consumed, in turn, wheat bran, senna, loperamide
      and bran shaped plastic flakes, each for 10 days with a minimum 2 week washout
      period between study periods, dietary intake being unchanged. Before and in the
      last 4 days of each intervention whole-gut transit-time, defecation frequency,
      stool form, stool beta-glucuronidase activity, stool pH and the absorption of a
      1.5 mg dose of oestradiol glucuronide were measured. RESULTS: Wheat bran, senna
      and plastic flakes led to the intended reduction in whole-gut transit-time,
      increase in defecatory frequency and increase in stool form score. Loperamide
      caused the opposite effect. The length of time the absorbed oestrogen was
      detectable in the serum fell with wheat bran and senna, although this was only
      significant for oestradiol. Oestrone, but not oestradiol, was detectable for a
      longer time with loperamide. Plastic flakes had no effect on either oestrogen.
      Areas under the curve did not change significantly but tended to fall with the
      three transit-accelerating agents and to rise with loperamide. CONCLUSION: Our
      data indicate there is likely to be an effect of intestinal transit on the
      absorption of oestrogens but more refined techniques are needed to characterize
      this properly.

PMID- 9512952
TI  - CagA protein seropositivity in a random sample of adult population and gastric
      cancer patients in Estonia.
AB  - OBJECTIVE: The prevalence of antibodies to CagA protein, associated with the risk
      of developing gastric cancer (GC), was studied in an Estonian adult population
      with a high prevalence of Helicobacter pylori (HP) infection and in a group of GC
      patients. DESIGN: In a representative sample of a random adult population from
      the South Estonian town of Karksi-Nuia, containing 199 subjects (86 M, 113 F,
      mean age 42.4) and in 45 (22 M, 23 F, mean age 64.5) consecutive patients with
      gastric adenocarcinoma, recruited during the periods 1986-87 and 1995-96 in the
      Hospital of Oncology, University of Tartu, anti-CagA IgG antibodies were
      determined by enzyme-linked immunosorbent assay (ELISA) using a recombinant
      fragment of CagA protein. The occurrence of anti-CagA IgG in ELISA was compared
      with immunoblot results for 141 subjects. RESULTS: Seropositivity to acid glycine
      extracted cell surface proteins of HP was 85% in the population and 91% in GC
      patients (p = 0.39). Anti-CagA IgG antibodies were present in 63% of the
      population and in 87% of GC patients (p = 0.004). The highest prevalence of anti
      CagA IgG in the population sample occurred in the age group 20-29 (76%). A
      comparison of anti-CagA positivity evaluated by using ELISA and immunoblot showed
      an agreement of results in 80% of cases. CONCLUSION: HP seropositivity was
      similarly high in the Estonian random adult population sample and in GC patients,
      however, the prevalence of anti-CagA IgG was significantly higher in GC patients.
      Moreover, persons aged 20-29 years in the population possess the highest
      prevalence of anti-CagA IgG and should be given further attention with respect to
      the development of GC later in life.

PMID- 9512953
TI  - Seroprevalence of Helicobacter pylori infection in Nepal: low prevalence in an
      isolated rural village.
AB  - OBJECTIVE: To determine the seroprevalence of Helicobacter pylori infection in
      Nepal. DESIGN: H. pylori infection was identified using a specific and sensitive
      enzyme-linked immunosorbent assay for anti-H. pylori immunoglobulin G. STUDY
      POPULATION: Serum samples were collected from 1142 inhabitants (age range 4-93
      years) from two villages: Kotyang, a rural isolated village (250 men, 210 women)
      and Bhadrakali, a suburban village of Kathmandu (334 men, 348 women). RESULTS:
      The overall prevalence of H. pylori infection was 56.8%, while significantly
      higher prevalence was found in the suburban village (Bhadrakali; 67.2%) than in
      the rural village (Kotyang; 41.5%). This difference was generally reflected by
      the infection rate in the 10-14-year-old age-group (Bhadrakali, 60% compared with
      Kotyang, 22.2%). The prevalence of infection significantly increased with age,
      while no significant difference was found in the prevalence of infection by
      gender. There was no difference in H. pylori positivity between individuals with
      and without upper abdominal symptoms in both villages. CONCLUSION: There was a
      significant regional difference in the seroprevalence of H. pylori within Nepal,
      which showed lower prevalence in an isolated rural village. This difference was
      mainly caused by the different acquisition rate in teenagers, thus indicating
      that the teenage lifestyle of this particular environment seemed to be the major
      determinant in the acquisition of H. pylori infection in the population.

PMID- 9512954
TI  - Antibiotic use, childhood affluence and irritable bowel syndrome (IBS).
AB  - BACKGROUND: Antibiotics cause well defined short-lived disturbances in bowel
      habit. There is evidence to suggest that antibiotics may play a role in the
      pathogenesis of IBS. Atopy has been associated with small household size in
      childhood and could also play a role in IBS. We conducted a survey examining the
      relation of drug use and other epidemiological correlates of IBS. SETTING:
      General practice health screening clinic. SUBJECTS AND METHODS: 421 subjects (46%
      male, mean age 47 years (range 18-80 years) attending a general practice health
      screening clinic were interviewed by a research nurse and completed a previously
      validated questionnaire. Symptoms of IBS were said to be present if abdominal
      pain with 2 or more Manning criteria symptoms occurred more than once per month
      over the previous 6 months. RESULTS: 48 subjects had symptoms of IBS. The
      following were strongly related to its presence: antibiotic use [adjusted OR 3.70
      (1.80-7.60)], female sex and childhood living density < 1 person per room [OR
      3.47 (1.57-7.64)], manual father's occupation [OR 0.35 (0.16-0.76)]. The use of
      NSAIDS, H2 antagonists or other types of medication was not greater in this
      group. CONCLUSION: Antibiotic use is associated with IBS. The association with
      antibiotic use requires testing in prospective studies. Privileged childhood
      living conditions were also an important risk factor which is consistent with an
      allergic aetiology for IBS.

PMID- 9512955
TI  - Are we telling patients enough? A pilot study to assess patient information needs
      in a gastroenterology outpatient department.
AB  - OBJECTIVE: To define whether gastroenterology patients wish to receive more
      information concerning many aspects of their illness and to elicit their attitude
      after receiving written communication from their hospital practitioner. METHODS:
      In stage 1, 73 gastroenterology patients were interviewed and completed a
      structured questionnaire after their hospital outpatient visit, to assess whether
      they would like to receive more information about their condition. Stage 2
      involved posting a copy of the general practitioner's letter, dictated in the
      clinic, to the patient and assessing their opinion of its value, by using a
      second questionnaire. In stage 3 a group of outpatients received a letter
      specifically prepared for them which summarized the outcome of their clinic visit
      (with avoidance of medical terms) and they again completed a questionnaire.
      RESULTS: More than 75% of patients wished to receive written communication from
      their hospital practitioner. Ninety percent wanted to know more about diagnostic
      tests and 92% requested more information about their medication. Ninety percent
      of patients who received a copy of their GP's letter claimed to understand its
      contents and felt it was beneficial. Ninety four percent wanted the service to
      continue. However, there was no advantage in preparing a special letter for
      patients compared with a simple copy of that sent to their GP. CONCLUSION: There
      is considerable interest amongst gastroenterology patients concerning their
      diagnosis and the management of their disease. The provision of simplified
      letters about their outpatient management does not seem to have any advantage
      over simply providing copies of all relevant correspondence sent to GPs.

PMID- 9512956
TI  - Changes in liver histopathology in women infected with hepatitis C through
      contaminated anti-D immunoglobulin injections in Ireland.
AB  - OBJECTIVE: To evaluate histological findings in untreated chronic hepatitis C
      patients at diagnosis 17 years after infection and to assess histological
      progression on repeat liver biopsy 2 years later. PATIENTS: Thirty patients
      infected with hepatitis C virus (HCV), genotype 1b, by contaminated anti-D
      immunoglobulin in Ireland in 1977 were studied. These patients were diagnosed in
      1994 for the first time. All patients were positive for HCV-RNA by polymerase
      chain reaction (PCR). METHODS: Each patient underwent two liver biopsies
      approximately 2 years apart 17 and 19 years after initial infection. The liver
      biopsies were scored by two pathologists by the modified histological activity
      index using a numerical score. At first liver biopsy at time of presentation,
      eight patients had normal alanine aminotransferase (ALT), four had an ALT of more
      than 100 IU/I and 18 had an ALT level between 40 and 100 IU/I. RESULTS: In the
      initial (1994) biopsies, the median grade (inflammation) was 5/18, range 1-9 and
      the median stage (fibrosis) was 2/6, range 0-6. One patient showed cirrhosis
      (stage 6/6) and six patients (20%) had developed moderate fibrosis (stage 3-4/6).
      On the repeat biopsy, 2 years later, median grade (inflammation) was 5/18, range
      2-9 and stage (fibrosis) was 1/6, range 0-6. CONCLUSION: This group of patients,
      infected with HCV genotype 1b and untreated for 19 years, allows evaluation of
      the natural history of this virus. The majority of patients showed mild chronic
      hepatitis. Only one patient had developed cirrhosis. There was no significant
      histological disease progression between the two biopsy specimens over a 2 year
      period. The results suggest that the prognosis in such cases could at least be
      guardedly optimistic and that sequential liver biopsy may be performed less
      frequently.

PMID- 9512957
TI  - Genotype distribution of hepatitis C virus infection in Greece: correlation with
      different risk factors and response to interferon therapy.
AB  - The aim of this study was to investigate the prevalence of HCV genotypes among
      Greek patients with chronic hepatitis C and to assess the influence of genotypes
      and quasi-species populations on efficacy of interferon therapy. Genotypes were
      determined in 65 patients (18 patients after kidney transplantation, 16 with
      thalassemia and 31 with no known risk factor) with elevated ALT for more than 6
      months and histologically proven chronic hepatitis, using the Inno-Lipa strip
      assay. The quasi-species were determined using the fluorescence single-strand
      conformational polymorphism method. Most patients were infected with genotype 3a,
      namely 61% of patients with kidney transplants (n = 18), 50% of patients with
      thalassemia (n = 16) and 48% of patients without known risk factors (n = 31).
      Other genotypes were found including coinfection with different genotypes. In all
      patients with mixed infection, genotype 3a was present. Thirty-six patients from
      the last two groups received interferon (3Mio U 3x week) for 1 year. Biochemical
      and/or virological and histological responses were found in 11/19 patients with
      genotype 3a (58%), 3/5 with mixed infection, 2/4 with genotype 1b, 2/5 with
      genotype 2a, 1/4 with genotype 1a and 1/1 with genotype 4. The virus found in non
      responders with genotype 3a was genetically more heterogeneous than in
      responders. These data indicate that (1) the genotype 3a is prevalent in Greek
      patients (68% of all patients), (2) there is no significant difference regarding
      genotypes among patients with different risk factors and (3) although based on a
      small number of patients, the genotype 3a seems to respond better to interferon
      therapy. Finally, the number of quasi-species may be a factor predictive of
      response.

PMID- 9512958
TI  - Endoscopic sclerotherapy for bleeding oesophagogastric varices secondary to
      extrahepatic portal vein obstruction in an adult Caucasian population.
AB  - BACKGROUND: The efficacy of endoscopic sclerotherapy for bleeding
      oesophagogastric varices secondary to extrahepatic portal vein obstruction in
      adult Caucasian patients is poorly documented. OBJECTIVE: To assess the results
      of endoscopic sclerotherapy for all patients with this condition who have been
      treated and followed in our hospital since 1982. DESIGN: Prospective cohort
      study. RESULTS: Twenty-one consecutive patients were included and followed during
      a mean period of 79 months (range 6-162 months). Active bleeding, encountered in
      five patients, was controlled by sclerotherapy in all cases. Two patients
      received a porto-systemic shunt after initial sclerotherapy. In all but one of
      the remaining 19 cases sclerotherapy resulted in eradication of the varices. The
      mean bleeding risk after initiation of sclerotherapy was 0.02
      bleed/month/patient, which was lower than the estimated 0.13 bleed/month/patient
      prior to sclerotherapy. The actuarial rate of rebleeding at 5 years due to all
      causes and due to oesophagogastric varices was 35 and 28%, respectively. Two
      patients died, both from a haematological (pre-) malignancy. Actuarial 5 year
      survival was 95%. CONCLUSION: The results of this study are in agreement with
      findings for paediatric and Asian patient populations and support sclerotherapy
      as the primary treatment modality for oesophagogastric variceal bleeding in adult
      Western patients with portal vein thrombosis. Life expectancy for patients with
      this condition is determined by the underlying cause of the portal venous
      obstruction.

PMID- 9512959
TI  - Prokinetics in the treatment of gastro-oesophageal reflux disease. International
      symposium. Paris, France, 5 September 1996.

PMID- 9512960
TI  - Sclerosing peritonitis complicated by sepsis: a potential cause of portal
      hypertension.
AB  - A 27-year-old woman with chronic renal failure, who had been treated with chronic
      ambulatory peritoneal dialysis and had developed sclerosing peritonitis, was
      admitted to the hospital with intra-abdominal sepsis. In spite of antibiotic
      therapy, sepsis recurred and was associated with intrahepatic cholestasis. In
      addition, over a period of about 4.5 weeks she developed hepatomegaly and portal
      hypertension unassociated with occlusion of the portal vein or one of its main
      extrahepatic branches. A wedge biopsy of the liver revealed extensive thick
      fibrosis of the liver capsule, intrahepatic cholestasis, diffuse swelling of
      hepatocytes, central veins that were difficult to visualize and small portal
      tracts. It is suggested that the sepsis was responsible for the intrahepatic
      cholestasis, swelling of hepatocytes and hepatomegaly. It is also suggested that
      the rigidity of the fibrotic liver capsule provided resistance to the development
      of hepatomegaly, with the result that intrahepatic pressure increased
      (compressing intrahepatic branches of the portal vein as well as portal tracts
      and central veins) and portal hypertension developed.

PMID- 9512961
TI  - Effect of a single oral dose of antioxidant mixture (vitamin E, carotenoids) on
      the formation of cholesterol oxidation products after ex vivo LDL oxidation in
      humans.
AB  - During oxidation of LDL not only polyunsaturated fatty acids and apolipoproteins
      but also cholesterol is affected. To test the preventive effect of vitamin E and
      carotenoids against metal ion-induced oxidative modification of the cholesterol
      moiety, LDL of five females (age 25-30 years) were enriched by single oral
      supplementation with a mixture of alpha-tocopherol, beta-carotene, lycopene,
      canthaxanthin, and lutein. LDL was isolated from blood samples before as well as
      10 and 24 hours after supplement intake. In the 10 and 24 hours samples, total
      concentration of the supplemented antioxidants increased significantly to 127%
      and 125% of the initial value, respectively. As a consequence, the lag phase
      until beginning of oxidative modification of fatty acids--measured in terms of
      lag phase time till diene production--significantly increased by 13% (10 h and 24
      h). After stopping the oxidation process in all LDL samples (0 h, 10 h, 24 h) of
      one person when the maximal absorbance value of diene production in the 10 h
      sample was reached, a statistically significant reduction in the formation of
      cholesterol oxidation products (COP) could be measured. In the average, 10 h and
      24 h after supplementation the COP concentration reached 84% and 86% of the 0 h
      value, respectively. Except for 7 beta-hydroxycholesterol, all COP measured
      decreased by 10-20%. The results of the in vitro-model demonstrate that an
      antioxidant enrichment of LDL has the potential to protect also cholesterol
      (besides unsaturated fatty acids) against oxidative modification.

PMID- 9512962
TI  - Liposomal doxorubicin in pulmonary Kaposi's sarcoma: improved survival as
      compared to patients without liposomal doxorubicin.
AB  - OBJECTIVE: Pulmonary Kaposi's sarcoma (KS) in HIV-infected patients is
      characterised by a poor prognosis with a mean survival time of 2 to 6 months. Our
      goal was to evaluate survival in patients with pulmonary KS treated with Stealth
      liposomal doxorubicin (SL-DOX) and to compare it with patients without SL-DOX
      therapy. PATIENTS AND THERAPY: 29 AIDS patients with confirmed pulmonary Kaposi's
      sarcoma were studied. Group 1 (n = 20): Patients treated with SL-DOX. Group 2 (n
      = 9): 4 patients who received bleomycin and vinblastine or vincristine and 5
      patients without chemotherapy. RESULTS: Survival analysis by Kaplan-Meier plot
      showed a significant benefit for patients with SL-DOX treatment. Mean survival
      times were 11.8 +/- 1.78 months (group 1: range 1-28) versus 4.4 +/- 1.68 months
      (group 2; range 1-17). Average CD4 levels did not differ significantly at
      diagnosis of pulmonary Kaposi's sarcoma. Clinical response included improvement
      of general health, particularly cough and dyspnea, of arterial pO2 and
      radiographic KS pattern in the lung. CONCLUSION: Our analysis suggests a clear
      survival and quality of life benefit for patients with pulmonary Kaposi's sarcoma
      on liposomal doxorubicin.

PMID- 9512963
TI  - Heterozygosity for the missense mutation Ala370-->Thr in exon 8 of the low
      density lipoprotein receptor gene does not cause hypercholesterolemia.
AB  - Familial hypercholesterolemia (FH) is caused by mutations in the low-density
      lipoprotein (LDL) receptor gene. We used a multiplex-PCR based single-strand
      conformation polymorphism analysis to screen the promotor region and all 18 exons
      of the LDL receptor gene for mutations in patients clinically diagnosed as having
      FH to identify their particular gene defect. An affected proband was found to be
      heterozygous for a missense mutation, replacing guanine to adenine at nucleotide
      1171 of exon 8 of the gene. This mutation is predicted to cause a substitution of
      alanine to threonine at codon 370 (A370T). The base exchange abolishes a HaeIII
      restriction site. PCR of exon 8 followed by restriction enzyme digestion with
      HaeIII conveniently allowed to screen the whole family and 101 unrelated
      normocholesterolemic subjects from the same ethnic background for the presence of
      this mutation. The A307T mutation did not cosegregate with the clinical phenotype
      of hypercholesterolemia in the affected family. Furthermore the mutation was
      identified in a heterozygous state in 12 out of 101 and in a homozygous state in
      1 out of 101 normocholesterolemic subjects, indicating that this mutation is a
      frequent genetic variation of the LDL receptor gene in the population examined.
      Lipid values of probands carrying the wild type LDL receptor allele and the
      mutation in a heterozygous state did not differ significantly. The proband
      carrying the mutation on both LDL receptor alleles had high normal cholesterol
      and LDL cholesterol levels. The A370T mutation represents the third single-amino
      acid change of the LDL receptor protein reported so far, which, in a heterozygous
      state, is not associated with the clinical phenotype of familial
      hypercholesterolemia. The pathophysiologic significance of homozygosity for this
      mutation remains to be clarified.

PMID- 9512964
TI  - First long-term results of imiglucerase therapy of type 1 Gaucher disease.
AB  - BACKGROUND/AIMS: In the early 1990s, enzyme replacement therapy with modified
      placental glucocerebrosidase (alglucerase, Genzyme Corporation, Cambridge, MA,
      USA) was shown to arrest or reverse complications and to improve quality of life
      in patients with type 1 Gaucher's disease. More recently, modified recombinant
      glucocerebrosidase (imiglucerase, Genzyme Corporation) has been shown to be safe,
      effective and clinically equivalent to alglucerase by two studies which presented
      data for 12 months' follow-up. This case report, with 30 months' follow-up,
      represents the first publication of long-term results of imiglucerase therapy of
      type 1 Gaucher's disease in Europe. METHODS: Retrospective analysis of safety and
      efficacy of 30 months' imiglucerase infusions, 40 U/kg body weight every 2 weeks
      for 17 months, then 60 U/kg every 2 weeks for 13 months, in an elderly male
      patient with severe type 1 Gaucher's disease. RESULTS: No adverse reactions
      occurred, and anti-imiglucerase antibody assay was negative at 17 months.
      Clinically, the patient responded rapidly and markedly. Within several months,
      bone pain decreased notably, enabling him to abandon crutches. Abdominal pain
      abated, fatigue decreased and physical fitness and general well-being improved.
      Nosebleeds and haematomas ceased. Dosage increase massively reduced
      hepatosplenomegaly and produced much greater improvement in laboratory values,
      especially platelet count. Bone pain diminished further, so that this formerly
      disabled patient now walks and climbs stairs without complains. Also of note,
      aminotransferases, gamma-GT, total protein, and prothrombine time improved,
      suggesting improvement of liver function. CONCLUSIONS: This case documents long
      term safety and efficacy of recombinant enzyme replacement in type 1 Gaucher's
      disease.

PMID- 9512965
TI  - Geriatrics in canine and feline internal medicine.
AB  - The increasing life expectancy in humans--at least in the developed countries-
      including all medical, social, and political consequences is a generally accepted
      phenomenon at the end of this century. In earlier examinations it could be
      noticed that also in dogs and cats a remarkable increase of the life span seems
      to occur in the last 15 years (Beelitz 1988; Danckert and Kraft 1997; Davis 1996;
      Eichelberg and Seine 1996; Goldston 1989; Kraft 1978, 1990, 1997 a-c; Kraft and
      Danckert 1997; Kraft et al. 1989; Pauling 1990; Trimborn 1990). If this is true,
      it could have a series of consequences not only for the veterinary practice but
      also for the comparative medicine. The aim of this paper was to examine a
      population of dogs and cats to find out, if the life span of these companion
      animals really increases and the consequences it may have for medical care. The
      following criteria were examined: (1) the distribution of the age of the dogs and
      cats at their last presentation as out-patients (2) the change of the age at
      which the animals died on an average (3) the influence of the breed on the life
      expectancy (4) the relation of the sex and expectation of life (5) age related
      multimorbidity (6) the appearance of the most common organ diseases and
      functional disturbances during the life span

PMID- 9512966
TI  - DNA diagnosis of familial hypercholesterolemia.
AB  - More than half of all deaths in western societies are related to arteriosclerotic
      cardiovascular diseases. Inherited disturbances in the low-density-lipoprotein
      (LDL) receptor and similar lipid-related defects account for more than half.
      Testing procedures thus far rely on lipoprotein determinations. These tests are
      not able to provide any genetic inference. We have developed an oligonucleotide
      ligation assay (OLA) which enables us to screen for high risk individuals by
      testing for common mutations in using automated genotyping equipment. Since the
      test is robust, reliable, objective, fool proof, and automated, it will be useful
      in screening large population to gather genetic epidemiological data, distinguish
      relative from absolute risk, as well as for cost effective case finding in family
      studies.

PMID- 9512967
TI  - Biliary excretion of benzbromarone and its hydroxilated main metabolites in
      humans.
AB  - Hepatic metabolism of the uricosuric drug benzbromarone results in the formation
      of two hydroxilated main metabolites M1 (1'-hydroxybenzbromarone) and M2 (6
      hydroxybenzbromarone). As urinary excretion of benzbromarone and its metabolites
      is very low, we investigated biliary and plasma concentrations of the parent drug
      and the metabolites after oral administration of a single 100 mg dose of
      benzbromarone in 6 patients requiring diagnostic gastroduodenoscopy.
      Benzbromarone, M1 and M2 were detectable in bile samples 12 hours after drug
      application. No dehalogenated derivatives (bromobenzarone, benzarone) were
      present in the bile. 12h, 24h, and 36h plasma concentrations of the parent drug
      and the main metabolites varied substantially. Our data provide direct evidence
      of biliary excretion of benzbromarone and its hydroxilated main metabolites 1'-OH
      bzbr (M1) and 6-OH-bzbr (M2) and demonstrate the lack of excretion of
      debrominated products.

PMID- 9512969
TI  - Periodontal disease in elderly patients.
AB  - In the elderly patients a greater loss of teeth is frequently seen in combination
      with periodontal diseases. This article presents an overview of the changes of
      oral structures during ageing as well as immunology, physical and psychological
      aspects. Also summarised are complications by systemic illnesses, drug
      medications and periodontal alterations. If possible illnesses and medications
      are taken into consideration, there should be no special problem for the elderly
      patients.

PMID- 9512968
TI  - Fenofibrate improves microcirculation in patients with hyperlipidemia.
AB  - In order to investigate the effect of fenofibrate on microcirculation, 16
      patients (5 female, 11 male, age 58 +/- 8 years) were studied with the aid of
      nailfold capillaroscopy before and after treatment with 200 mg fenofibrate per
      day over six weeks. Fenofibrate resulted in a significant decrease in
      triglycerides, total and LDL-cholesterol and apolipoprotein B and an increase in
      apolipoprotein A. As a parameter of an improved microcirculation the time to peak
      capillary blood cell velocity during postreactive hyperemia (occlusion of the
      lower arm for 2 minutes, 200 mmHg) decreased markedly from 45 +/- 5 to 16 +/- 3
      s, p < 0.0001). Fibrinogen levels were significantly decreased (p < 0.04) in
      contrast to other parameters with a possible impact on microvascular perfusion
      (hemoglobin, hematocrit, mean platelet volume, total protein) and to blood
      pressure and heart rate. These findings suggest that fenofibrate treatment
      improves microcirculation in patients with hyperlipidemia. This beneficial effect
      of fenofibrate may arise from two leading mechanisms. One of these might be the
      decrease in fibrinogen levels reducing plasma viscosity, the other mechanism
      might be an indirect effect on functional abnormalities of the vascular
      endothelium arising from hyperlipdidemia. By lowering plasma lipids fenofibrate
      is likely to restore the impaired formation or efficacy of the endothelium
      derived relaxing factor (nitric oxide, NO).

PMID- 9512970
TI  - Quantification of fecal alpha 1-antitrypsin excretion for assessment of
      inflammatory bowel diseases.
AB  - Determination of fecal excretion of the serum proteinase inhibitor alpha(1)
      antitrypsin (AAT) is established for quantification of intestinal protein loss.
      It was demonstrated to be increased both in quiescent and in active inflammatory
      bowel diseases (IBD, Crohn's disease and ulcerative colitis). The
      (patho)physiological rationale for measuring fecal AAT excretion and its role in
      the diagnostic and prognostic assessment of these disorders will be critically
      reviewed. Experimental and clinical data were selected from computerized MEDLINE
      literature search, manual review of bibliographies, and personal experiences of
      the authors. In IBD patients, fecal AAT excretion corresponds to gross assessment
      of clinical disease activity, endoscopic degree of intestinal inflammation, and
      any response to treatment. It appears to be an early indicator of subclinical
      bowel disease and its imminent exacerbation. However, there is neither strict
      correlation to summarizing clinical disease activity indices, nor to extent or
      location of intestinal inflammation. Fecal AAT excretion was also found to be
      elevated in active pouchitis, and to correlate to its severity. In summary,
      estimation of fecal AAT excretion is a sensitive, but non-specific parameter
      reflecting enteric inflammation in IBD individuals. It proved to be an
      independent supplementary variable for monitoring their intestinal disease
      activity, with some predictive value for their forthcoming clinical course.

PMID- 9512971
TI  - Indication for a specific interaction of fatty acids with a liver sinusoidal
      plasma membrane carrier.
AB  - To evaluate whether fatty acids interact specifically with plasma membrane
      proteins, binding of [3H]oleate to rat liver plasma membranes was determined
      after exposure of the plasma membranes to temperatures of 40 to 95 degrees C for
      15 min. Starting at 50 degrees C, membrane binding of [3H]oleate gradually
      decreased, reaching at 95 degrees C a 58.2% inhibition of binding compared to
      control values obtained at 18 degrees C. Another criterion of specific
      interaction with a membrane transport protein was the observation that two
      different long chain fatty acids, palmitate and oleate, compete for uptake in the
      experimental system of the isolated perfused rat liver. Both observations support
      the hypothesis that hepatocellular uptake of fatty acids represents a carrier
      mediated transport mechanism and not simple diffusion.

PMID- 9512972
TI  - Disease-specific noncompliance with drug treatment as a cause of persistent
      hyperuricemia and gout in anorexia nervosa.
AB  - A 49 year old female patient with anorexia nervosa was admitted to the hospital
      because of treatment-refractory hyperuricemia and gout. Medical history and
      clinical findings were compatible with primary gout and uric acid nephropathy.
      The patient stated that she regularly took allopurinol. In the hospital she
      initially received 300 mg allopurinol daily after breakfast. In order to ensure
      allopurinol ingestion and absorption the plasma concentrations of both
      allopurinol and its active metabolite oxipurinol were determined in addition to
      serum uric acid and further clinical chemistry data. Despite allopurinol
      treatment no decrease of serum uric acid was observed for three days. Therefore
      the head nurse was instructed to supervise the intake of allopurinol carefully.
      During the following days serum uric acid decreased and plasma oxipurinol
      concentrations rose. On day 9 of treatment serum uric acid fell into the upper
      normal range. Therefore the patient was allowed to leave the hospital within a
      few days. However serum uric acid thereafter increased again while plasma
      oxipurinol declined. Later on it became evident that the patient had vomited self
      induced approximately 15 minutes after allopurinol intake. In the meantime her
      husband had urged her to return home. Starting with day 18 benzbromarone
      treatment was added. Combined therapy with 400 mg allopurinol and 50 mg
      benzbromarone daily finally resulted in a serum uric acid concentration of 4.5
      mg/dl at discharge from the hospital. About three weeks later the private
      physician again diagnosed hyperuricemia with serum uric acid values between 10
      and 12 mg/dl. Meanwhile the patient needs to be dialysed due to end stage renal
      disease. Our observations show that self-induced vomiting to prevent effective
      treatment may be a disease-specific pattern of noncompliance with drug therapy in
      anorexia nervosa.

PMID- 9512973
TI  - PICP as bone formation and NTx as bone resorption marker in patients with chronic
      renal failure.
AB  - Renal bone disease which develops in patients with chronic renal failure (CRF) is
      not a uniform metabolic disorder. Although bone histomorphometry is accepted to
      be the gold standard for characterizing the state of disease progression, the
      techniques involved are cumbersome and expensive so that it cannot be used
      routinely. As a result, numerous biochemical markes have been developed to
      measure bone formation and resorption. The purpose of this study was to evaluate
      the suitability of procollagen type-I C-terminal peptide (PICP) in serum as an
      indicator of bone formation and cross-linked amino-terminal telopeptide of type I
      collagen (NTx) in urine as an indicator of bone degradation processes, and to
      investigate their relation to histomorphometric and other biochemical parameters.
      77 patients with CRF and 49 patients on intermittent hemodialysis treatment (DT)
      were investigated. PICP was measured in serum and NTx in urine. In addition,
      iPTH, phosphate, calcium, alkaline phosphatase (APH), osteocalcin and creatinine
      in serum were determined. Bone biopsies were obtained from the anterior, superior
      iliac crest, and the histomorphometric parameters were measured and expressed
      according to the standardized nomenclature. Patients with CRF and DT had
      significantly higher PICP and NTx levels as compared to controls. In the CRF
      group significant correlations could be obtained between PICP and
      histomorphometric parameters of bone formation as well as between NTx and
      histomorphometric indices of bone resorption. In this group, PICP levels were
      positively correlated to iPTH, phosphate and creatinine levels and negatively to
      calcium concentrations. Furthermore, there were significant correlations between
      NTx values and those of both iPTH and APH. In the group of dialysis patients,
      levels of PICP and NTx did not correlate with any of the histomorphometric
      parameters or the classical humoral markers. CONCLUSIONS: The results suggest
      that PICP as bone formation and NTx as bone resorption markers are of potential
      use for screening bone turnover in predialysis chronic renal failure patients.
      But in patients undergoing dialysis, neither PICP nor NTx yielded any substantial
      information as noninvasive markers of bone histology.

PMID- 9512974
TI  - Immaturity alters plasma lipoprotein composition of intravenously alimented
      newborn infants.
AB  - Plasma lipoprotein composition in infants receiving fat-free parenteral nutrition
      reflects the endogenous synthesis and metabolism of lipids. We studied the
      composition of plasma lipoproteins in 49 appropriate for gestational age newborn
      infants after surgery who received only glucose and amino acid solutions for 5.4
      +/- 0.3 days (M +/- SE). Of the infants studied, 31 were fullterm (gestational
      age 39.5 +/- 0.2 weeks) and 18 premature (34.3 +/- 0.7 weeks). Plasma lipid
      levels (total lipids, triglycerides, free cholesterol, sterol, esters,
      phospholipids) did not differ between term and premature infants, but
      triglycerides and cholesterol were markedly lower than in young, fasting adults.
      The contribution of triglycerides to lipoprotein lipids was strikingly low in
      chylomicrons (21% vs. 90% in young fasting adults) and VLDL (34 vs 60%) and the
      infants had a consistently lower cholesterol content of HDL (21 mg/dl vs. 45-50
      mg/dl in adults) and LDL (43 mg/dl vs. 100 mg/dl). All infantile lipoproteins
      were enriched with phospholipids. These results are comparable to those reported
      for cord plasma. In premature babies, VLDL were markedly reduced and contained
      less triglycerides, free and esterified cholesterol than in term infants. In
      contrast, HDL were increased in preterm infants and carried more phospholipids.
      VLDL contributed to al lesser and HDL to a greater extent to plasma lipid
      transport in premature infants. We conclude that in premature infants hepatic
      synthesis of triglycerides and cholesterol and their secretion as VLDL is
      reduced, which may be caused by low substrate availability or an immaturity of
      the synthetic pathway. In premature infants, HDL appears to play a major role in
      transporting plasma lipids to peripheral tissues.

PMID- 9512975
TI  - Karnofsky's score modified for cats.
AB  - The index of Karnofsky evaluating quality of life was originally developed by
      David A. Karnofsky in 1948. It determines the ability of a patient to carry on
      normal activities in life by using a scale from 0 to 100%. This index was
      modified for the cat. The index enables judgment of life quality and well-being
      in cats which is very difficult to interpret. Objectivity is given by a
      classification orientated in details concerning general condition as well as
      eating, playing, sleeping, and social behavior.

PMID- 9512976
TI  - Intracranial microembolic signals in patients with artificial heart valves:
      drowning in numbers.
AB  - Five years after the first description of Doppler microembolic signals, both
      their clinical significance and underlying material remain a matter of debate. It
      appears certain that MES depend on valve type and position, while their relation
      to other clinical parameters, including neurological complications, is still
      unclear. A number of clinical and experimental studies are reviewed, most of
      which argue towards gaseous embolic material.

PMID- 9512977
TI  - Urodilatin, a natriuretic peptide with clinical implications.
AB  - Natriuretic peptides (NP) constitute hormonal systems of great clinical impact.
      This report deals with Urodilatin (URO), a renal natriuretic peptide type A. From
      the gene of NP type A, a message for the preprohormone is transcribed in heart
      and kidney. The cardiac prohormone CDD/ANP-1-126 is synthesized in the heart
      atrium and processed during exocytosis forming the circulating hormone CDD/ANP-99
      126. URO (CDD/ANP 95-126) is a product from the same gene, but differentially
      processed in the kidney and detected only in urine. Physiologically, URO acts in
      a paracrine fashion. After release from distal tubular kidney cells into the
      tubular lumen, URO binds to luminal receptors (NPR-A) in the collecting duct
      resulting in a cGMP-dependent signal transduction. cGMP generation is followed by
      an interaction with the amiloriode-sensitive sodium channel which induces
      diuresis and natriuresis. In this way, URO physiologically regulates fluid
      balance and sodium homeostasis. Moreover, URO excretion and natriuresis are in
      turn dependent on several physiological states, such as directly by sodium
      homeostasis. Pharmacologically, URO at low dose administered intravenously shows
      a strong diuretic and natriuretic effect and a low hypotensive effect. Renal,
      pulmonary, and cardiovascular effects evoked by pharmacological doses indicate
      that URO is a putative drug for several related diseases. Clinical trials show
      promising results for various clinical indications. However, the reduction in
      hemodialysis/hemofiltration in patients suffering from ARF following heart and
      liver transplantation, derived from preliminary trials recruiting a small number
      of patients, was not confirmed by a multicenter phase II study. In contrast, data
      for the prophylactic use of URO in this clinical setting suggest a better outcome
      for the patients. Furthermore, treatment of asthmatic patients showed a
      convincingly beneficial effect of URO on pulmonary function. Patients with
      congestive heart failure may also profit from URO treatment, as it increases
      stroke volume and PCWP. Moreover, preliminary results from recent studies
      indicate that URO may also be effective in patients suffering from hepato-renal
      syndrome.

PMID- 9512978
TI  - Effects of omega-3 fatty acids on renal function and electrolyte excretion in
      aged persons.
AB  - Prostaglandin (PG) E2 formation, especially relevant for renal function in the
      state of renal vascular disease, is inhibited by omega-3 fatty acids. On the
      other hand, omega-3 fatty acids are under evaluation in chronic inflammatory
      kidney diseases, because of their ability to modulate immunologic cell response.
      We evaluated the effect of 1.7 g/d eicosapentaenoic acid (EPA), given with cod
      liver oil for four weeks to elderly persons with atherosclerosis. Enrichment of
      EPA coincided with inhibition of PG biosynthesis, transiently plasma creatinine
      increased, while creatinine clearance and excretion of solutes with the urine
      decreased in our experimental subjects. At the end of the four week study no
      effect of omega-3 fatty acids on renal function was found. Further studies are
      warranted to evaluate the potential benefit of omega-3 fatty acids on renal
      function in elderly persons.

PMID- 9512979
TI  - Learning at the computer: evaluation of an intelligent tutoring system.
AB  - The aim of the study was to test the efficacy of a new courseware. In a pre and
      post test frame, students were given the software to be used during one semester.
      A significant increase in the students' general study motivation was shown at the
      end of the semester. A change in the use and attitudes towards computers could
      not be observed. In a follow-up survey at the end of the semester, the students
      stated that the program was indeed helpful and useful but that they have had
      difficulties with the program's technical aspects and the general use.
      Furthermore, the results show that the majority of the participating students
      accepted the program's content, the general study motivation was high and the
      students showed a significant increase in learning gains, determined by the
      differences from pre and post test values. Especially students with low pre test
      values seemed to profit from the additional use of learning material, resp. the
      presented courseware. At the end of the semester the students with low and middle
      pre test results showed an increase in performance as well as an alignment in the
      performance for diagnosing rheumatological diseases to the students of the upper
      third pre test results.

PMID- 9512980
TI  - [Migraine in children is frequently unrecognized].

PMID- 9512981
TI  - [Chronic visual hallucinations and illusions following brain lesions. A single
      case study].
AB  - Lesions of the visual system do not necessarily lead to deficits in visual
      function. In some cases, there may even occur Positive Spontaneous Visual
      Phenomena (PSVP) following cerebral damage. We present data from a male patient
      with continuous, long-term visual illusions after having experienced cerebral
      infarction at the age of 56. Basing on conventional Magnetic Resonance Imaging,
      lesions could be located in areas supported by the lateral and medial occipital
      artery. Initially, homonymous hemianopsia of the right visual field was found in
      perimetric examinations, but in the course of six months, visual function
      recovered completely. Ever since the incident, the patient has been suffering
      from permanent photopsia, intense colourful visual hallucinations and
      perseverations located in the former defective area which continued unabated even
      after the remission of his visual field defects. While many authors have
      published data on PSVP lasting for several seconds, usually vanishing completely
      within days or weeks after cerebral lesion, in our patient the symptoms continued
      over a period of so far nine months. Surprisingly, he was even able to make
      drawings of his illusions so that we were able to include some of his pictures.

PMID- 9512982
TI  - [The incidence and significance of unusual neurologic signs. A clinical study].
AB  - Little is known about extrinsic-intrinsic reflexes, especially the prototype
      combinative extensor hallucis response, which become apparent if proprioceptive
      and exteroceptive afferents of the concerning muscles are stimulated
      simultaneously as well as successively. With reference to this phenomenon, data
      from 604 patients were evaluated under neurological aspects. With the exception
      of the combinative reflex of the peroneal muscles, the occurrence of other
      combinative reflexes (of tibial posterior, anterior and extensor hallucis
      muscles) was of clinical relevance. All these characteristics, in the same way as
      Tramer's reflex and unilateral tibialis posterior reflex, correlated very well
      statistically with typical symptoms of an upper motor neurone syndrome. In this
      context the extensor hallucis combinative response is the most important one.
      This particular sign occurred in a systematically examined population of patients
      twice as often as Babinski's sign and was the single reflex anomaly in 7 per cent
      of 200 systematically examined cases. A double-sided manifestation, which could
      be seen exclusively as physiological, appeared in less than 2 per cent of 604
      cases. In respect of the occurrence of combinative responses, patients belonging
      to different diagnostic groups, infants as well as adults, did not have
      statistically the same basic probability with regard to the examined neurological
      signs. Hence, an examination of healthy persons would not yield essential
      evidence. In our opinion such combinative reflexes and the other symptoms
      mentioned may be useful in detecting latent upper motor neuron lesion or may be
      helpful in doubtful cases. Whether or not the phenomenon of a combinative reflex
      really represents part of the latent pathognomonic flexor withdrawal reflex,
      cannot be decided with our clinical methods.

PMID- 9512984
TI  - [Perception, mimesis and consciousness].
AB  - Questions as to the fundamentals of "consciousness" are envisaged, first of all,
      from the viewpoint of quantifying experiments on visual perception in humans,
      focussed on "internal censorship", the role of intrapsychic mechanisms processing
      and correcting perception, and secondly based on recent theories on "mimesis" in
      the sense of R. Girard's concept of psychosocial transfer of aims and values
      between humans. The paper demonstrates a convergence between these two strategies
      of understanding, pointing to the view that "consciousness" may be interpreted as
      the performance of the intrapsychic "translation" between "cognitive" and
      "assessing" (or "valuating") emotional processes.

PMID- 9512983
TI  - [Neuropsychological and psychopathologic changes following cardiac surgical
      procedures].
AB  - Neuropsychological and neuropsychiatric disorders following open heart surgery
      are estimated to occur in as many as 80 per cent of all patients. They have been
      recognised from the very beginning of modern heart surgery. Despite a huge amount
      of scientific literature, data concerning incidence, the phenomenology and
      duration of symptoms diverge. This finding may be explained by heterogeneous
      aetiopathogenetic concepts and methodological and terminological problems
      associated with the investigation of postoperative delirium or neuropsychological
      and psychopathological sequelae of cardiac surgery. Nowadays, most authors agree
      in respect of a multifactorial pathogenesis of cognitive deficits following
      cardiac surgery. Factors influencing the psychopathological and
      neuropsychological outcome of cardiac surgery can be divided into pre-, intra-
      and postoperative variables. Advanced age, degree of cardiovascular impairment
      and other case histories, as well as history of drug abuse, are those
      preoperative variables that may be responsible for a postoperative cognitive
      decline. The predictive value of personality traits (depression and/or anxiety),
      however, is most controversial. Among the intraoperative variables related to the
      postoperative cognitive state, are e.g. the type of operation and technical
      procedure (micro-/macroembolism due to the way of oxygenation, pulsatile/-non
      pulsatile flow) and duration of extracorporeal circulation. In the postoperative
      period, the duration of intubation or ICU stay and related variables (like sleep
      or sensory deprivation/hyperstimulation) were identified as significant
      predictors of neuropsychological and psychopathological alterations. Modern
      research focusses on neurobiochemical markers of brain injury which may serve as
      early predictors of a postoperative cognitive decrease. These parameters may
      indicate an early postoperative diagnosis and neuroprotective treatment in
      patients at risk.

PMID- 9512985
TI  - [Max Scheler and Kurt Schneider. Scientific influence and personal relationship].
AB  - Two years after Kurt Schneider had finalised his thesis qualifying him as a
      lecturer at Cologne University, he completed his doctorate dissertation in
      philosophy, also at Cologne University. His advisor was Max Scheler. Schneider
      published the results of his researches in a short monograph. It appears that at
      this time Scheler's phenomenology began to influence psychiatry. However, Kurt
      Schneider made only passing references to Max Scheler in this regard.
      Nevertheless, Scheler's influence on Schneider remained noticeable even in his
      most famous book "Clinical Psychopathology". Years after their academic contacts,
      Scheler, on several occasions, asked Schneider's advice concerning his
      psychically disturbed son Wolfgang. Schneider's diagnosis amounted to a case of a
      severely psychopathic personality. He informed Max Scheler on this and,
      subsequently, Wolfgang Scheler was interdicted, i.e. legally incapacitated.

PMID- 9512986
TI  - Immune responses of cattle to African trypanosomes: protective or pathogenic?
AB  - Trypanosomosis in domestic livestock negatively impacts food production and
      economic growth in many parts of the world, particularly in sub-Saharan Africa.
      Current methods of control are inadequate to prevent the enormous annual socio
      economic losses resulting from this disease. Hope for a vaccine based on the
      variant surface glycoprotein coat was abandoned several years ago when the
      complexity of the parasite's antigenic repertoire was appreciated. As a result,
      research is now focused on identifying invariant trypanosome components as
      potential targets for interrupting infection or infection-mediated disease. The
      identification of immune mechanisms involved in parasite and disease control, or
      conversely those responses that are associated with a poor clinical outcome,
      should facilitate the search for vaccine candidates and subsequent vaccine design
      strategies. To this end, comparative studies on the immune responses of
      trypanotolerant and trypanosusceptible breeds of cattle can be exploited. These
      studies have revealed that trypanotolerant and trypanosusceptible breeds of
      cattle have distinct antibody responses. Trypanosusceptible cattle produce high
      titres of polyspecific IgM but fail to produce IgG to specific trypanosome
      antigens. In contrast, although T cell and macrophage/monocyte responses of
      infected cattle are depressed, significant differences have not been described
      between tolerant and susceptible breeds of cattle. In this review, isotype
      dependent effector mechanisms, such as complement activation, binding to Fc
      receptors, activation of phagocytic cells, neutralisation of parasite components,
      clearance of immune complexes and autoimmune responses, are discussed in the
      context of their potential impact on either susceptibility or tolerance of cattle
      to trypanosomosis. In addition, the links between specific cytokine patterns,
      macrophage/monocyte activation and depressed T cell responses that occur during
      trypanosome infection are presented. The identification of mechanisms that
      mediate depressed immune responses might suggest novel disease intervention
      strategies.

PMID- 9512987
TI  - Pneumocystis carinii in wildlife.
AB  - Pneumocystis carinii is a eukaryotic organism capable of causing life-threatening
      pneumonia (PCP) in immunocompromised hosts. Despite intensive investigation in
      human and laboratory animal hosts, information on the occurrence and nature of
      infections in wild animals is scarce, although characterisation of infections in
      wild-animal populations may help to elucidate the life-cycle and transmission of
      this elusive organism. Due to the interspecific differences in prevalence and
      intensity of P. carinii infection, and to the antigenic and genetic diversity of
      P. carinii organisms originating from various host species, which may affect the
      infectivity and pathogenicity of these organisms, we should be cautious when
      making generalisations about the nature of P. carinii infection. This review
      summarises the present state of knowledge on the occurrence of P. carinii in wild
      mammals in their natural habitats, and briefly discusses various characteristics
      of P. carinii infection important for understanding the distribution and
      abundance of this organism. Some aspects of P. carinii infection in wild hosts of
      particular interest for future research in this field will also be discussed.

PMID- 9512988
TI  - Host range and the maintenance of Haemonchus spp. in an adverse arid climate.
AB  - Three Haemonchus species (Haemonchus contortus, Haemonchus placei and Haemonchus
      longistipes) live in sympatry in Sahelian areas such as Mauritania (West Africa).
      Four host species (dromedary, zebu cattle, sheep and goats) share the same
      pastures for several months per year. Experimental infection by H. contortus or
      H. placei was achieved only poorly in dromedaries, and H. contortus or H.
      longistipes infection failed to establish in zebu cattle. Conversely, H. placei
      and H. longistipes successfully infected sheep and goats. Under field conditions,
      mixed congeneric infections were very rare in dromedaries but frequent in zebu
      cattle (H. contortus represented 16% of Haemonchus spp. burden), in sheep (H.
      placei: 15%) and in goats (H. placei: 9% and H. longistipes: 6% of worms). The
      importance of the different host species was evaluated for Haemonchus spp.: small
      ruminants are the main hosts of H. contortus, dromedaries harboured the large
      majority of H. longistipes worms but 5% of them were found in goats which seemed
      to be additional hosts. The most striking finding was the role played by the
      small ruminants in the survival strategy of H. placei in Sahelian regions: 56% of
      the total of H. placei worms were found in sheep, 34% in goats and only 10% in
      zebu cattle. These results are consistent with the hypothesis that the extension
      of host range plays an important role in the survival strategy of H. placei,
      whereas H. longistipes or H. contortus might well survive utilising their usual
      hosts.

PMID- 9512989
TI  - Assemblages of ectoparasites of a pelagic fish, slimy mackerel (Scomber
      australasicus), from south-eastern Australia.
AB  - Four-hundred and fifty-three Scomber australasicus, ranging in length from 14.1
      to 46.5 cm and taken in 12 samples over 5 years from a single locality in south
      eastern Australia, were examined. Ten species of ectoparasites were recorded: six
      monogeneans, three copepods and one isopod. The maximum number of parasite
      species in any one fish reached five, and the maximum total parasite intensity
      reached 39. Host size is an important determinant of the structure of
      ectoparasite assemblages of slimy mackerel: the average number of species per
      host peaked at 2.2 in fishes between 20 and 25 cm in length, then declined in
      larger fish; the abundance of all parasites on each fish similarly peaked in
      fishes 20-25 cm (mean of 9.9). The monogenean Pseudokuhnia minor had the highest
      prevalence and abundance of all parasites, infecting almost 80% of fish < 25 cm
      long. Over half of the total number of parasites belonged to this species, and it
      was dominant in intensity in just over half of the fish in which it occurred.
      When approximate volume was considered, assemblages were dominated by Kuhnia
      scombercolias in fish < 20 cm, by Kuhnia scombri in fish 20-34.9 cm, and by P.
      minor in fish larger than 35 cm long. The intensities of these three monogeneans
      were very strongly and positively correlated with each other, as were the
      intensities of P. minor and Grubea australis; the intensities of only one pair of
      species were associated negatively (K. scombercolias and the isopod Ceratothoa
      imbricata). A nested subset analysis indicates that the ectoparasite assemblages
      are random. This and the low prevalences and abundances of infection, as well as
      low species richness per fish, indicate that infra-assemblages are isolationist.

PMID- 9512990
TI  - The effect of anti-sandfly saliva antibodies on Phlebotomus argentipes and
      Leishmania donovani.
AB  - A study was undertaken to find the effect of repeated bites of the sandfly,
      Phlebotomus argentipes, on its host as well as on the vector itself. The study
      also aimed to find the effect of the immune serum on the parasite, Leishmania
      donovani, naturally transmitted by the vector. The hamster which was exposed to
      sandfly feeding showed good antibody titre against the sandfly salivary-gland
      secretion, which indicates that the salivary-gland secretion is immunogenic in
      nature. The result also revealed that the feeding attraction of the females,
      which has been expressed as the percentage of engorgement, gradually decreased as
      the mortality rate increased during the subsequent bites. Similar mortality rate
      was observed when the flies were fed with the immune sera through an artificial
      membrane feeding method. When the sandflies were fed both with the immune sera
      and the blood-parasite (L. donovani) suspension, in addition to the major loss of
      the number of vectors, there was an inhibition of development in the gut and a
      concomitant reduction in the migration of the parasite in the surviving females.
      These results indicate that the anti-sandfly saliva immune sera probably bind
      with the respective antigen-presenting sites of the sandfly salivary gland and,
      thus, cause the sandfly death. The possible explanation of the inhibition of the
      forward movement of the parasites is that the attraction of the parasites to the
      oesophagus, mediated by the sandfly saliva, is inhibited by the anti-saliva
      antibodies. The importance of anti-sandfly saliva antibodies as a tool of vector
      control and also to block the transmission of leishmaniasis has been indicated.

PMID- 9512991
TI  - Seasonal dynamics and variation among sheep in densities of the sheep biting
      louse, Bovicola ovis.
AB  - Cyclic patterns and variations among sheep in numbers of Bovicola ovis are
      described in Polypay and Columbia ewes that were initially infested with equal
      numbers of lice and penned indoors continuously for 2 years. Bovicola ovis
      populations were censused at 3-4-week intervals at 69 body sites on each animal.
      In the second year of the study, the ewes were reinfested and half were mated.
      Louse populations were monitored on the resulting lambs from birth until 25 weeks
      of age. Strong seasonal cycles in louse numbers were observed on the ewes, with
      peaks in spring and troughs in summer. These cycles occurred in the absence of
      shearing, direct solar radiation or rainfall. Populations began to decline when
      daily mean and maximum temperatures were 11.5 degrees C and 15 degrees C,
      respectively, well below temperatures thought to cause warm season decline. Louse
      densities on Polypay ewes were approximately 10 times higher than on Columbias at
      most inspections. There were also large differences among sheep within breeds and
      sheep counts were highly correlated among dates, both within and between years.
      One third of the ewes failed to become infested despite having lice applied on
      five separate occasions and being penned together with other infested sheep.
      Pregnancy and lactation did not significantly affect louse numbers on the ewes.
      There was a significant negative correlation between louse counts and weight
      gains in the lambs, and lamb counts were significantly correlated with those of
      their dams up until, but not after, weaning. It is suggested that sheep may exert
      regulatory influences on lice which contribute to cycles in B. ovis populations.

PMID- 9512992
TI  - Serum IgE responses during primary and challenge infections of sheep with
      Trichostrongylus colubriformis.
AB  - Serum IgE responses during primary or challenge infections with Trichostrongylus
      colubriformis were examined by measuring total IgE and parasite-specific IgE by
      ELISA. Three- to four-month-old lambs reared nematode-free received a single
      primary infection of 30,000 T. colubriformis-infective larvae (TcL3). Infections
      were terminated after 100 days by anthelmintic treatment, at which time faecal
      egg counts had fallen to low levels. Total serum IgE increased slowly from 20
      days p.i. until anthelmintic treatment. The specific IgE response to T.
      colubriformis adult antigen peaked at 20-27 days p.i. before returning to near
      baseline levels. A further slight increase occurred between 56 and 100 days p.i.
      The animals were then divided equally into two groups. A first series of
      challenge infections consisting of either weekly 10,000 TcL3 infections (Group A)
      or a single 30,000 TcL3 infection (Group B) produced low faecal egg counts. Total
      and specific IgE to adult and L3-ES antigens increased rapidly over a 21-day
      period, then remained elevated irrespective of challenge regime. Termination of
      primary and the first challenge infections with anthelmintic resulted in a rapid
      decline in serum IgE responses but not other T. colubriformis-specific Ig
      responses. A second series of challenge infections consisting of repeated 10,000
      (Group A) or 20,000 TcL3 infections (Group B) resulted in all IgE responses
      peaking within 7-8 days p.i. Marked softening of faeces coincided with peaks of
      specific and total IgE responses during challenge infections. The results of this
      study showed that infection of sheep with T. colubriformis leads to elevated
      levels of total and parasite-specific IgE in serum. IgE responses following
      challenge suggest involvement of this antibody isotype in protection from T.
      colubriformis infections.

PMID- 9512993
TI  - Mapping of linear B-cell epitopes on the 14-kDa fatty-acid binding protein of
      Chinese Schistosoma japonicum.
AB  - The 14-kDa fatty-acid binding protein (FABP) of schistosomes is of recognised
      importance as a potential vaccine and/or drug target against schistosomiasis, but
      little is known of its antigenicity. In this study, we have identified and
      compared linear B-cell epitopes present on the FABP of Chinese strain Schistosoma
      japonicum, using sera obtained from experimentally infected mice, or from mice
      immunised with the functionally active recombinant antigen (rSjFABP). Sera from
      three strains of mice, CBA, C57BL/6 and BALB/c, representing different genetic
      backgrounds, were reacted with a series of overlapping peptides in epitope
      scanning studies. Sera from experimentally infected mice reacted predominantly
      with peptides 9-12, encoding amino acids 91-132, in the C-terminal region of the
      molecule. This was in contrast to sera from mice immunised with rSjFABP, which
      reacted predominantly with peptides 4-9, encoding amino acids 41-101, in the
      central portion of the molecule. The results presented here describing the
      epitope mapping of this molecule may prove important in research aimed at further
      defining immune responses to schistosomal antigens. They indicate that epitopes
      recognised during vaccination with functionally active rSjFABP, at least in the
      murine model, differ from those recognised during natural infection.

PMID- 9512994
TI  - Effects of temperature on oviposition rate in Protopolystoma xenopodis
      (Monogenea: Polystomatidae).
AB  - Protopolystoma xenopodis is an oviparous monogenean occurring as an adult in the
      urinary bladder of the African clawed toad, Xenopus laevis. Egg production was
      monitored in two groups of infected hosts exposed to decreasing environmental
      temperatures. Despite possible upward trends in reproductive capacity with
      parasite age, oviposition rate was severely depressed at lower temperatures. In
      one experiment, egg production was monitored in a sample of seven hosts at 2
      degrees C intervals between 20 and 8 degrees C. Overall mean egg production rate
      showed a consistent decline from 11.9 eggs/worm/day (e/w/d) at 20 degrees C (days
      1-10) to 0.9 e/w/d at 8 degrees C (days 115-124). In a second experiment (n = 11
      hosts) oviposition rate was recorded at the same intervals between 20 and 6
      degrees C and then hosts were returned to 20 degrees C. Overall mean egg
      production rate decreased consistently from 4.1 e/w/d at 20 degrees C (days 1-10)
      to 0.2 e/w/d at 6 degrees C (days 124-131), at which temperature all infections
      continued to produce eggs. When parasites were then returned to 20 degrees C (141
      150 days), mean oviposition rate at this temperature (12.7 e/w/d) was found to
      have increased by 310% from the start of the experiment (130 days earlier) and by
      6350% from production at 6 degrees C (9 days earlier). P. xenopodis has been
      introduced to South Wales, U.K. and present results show that it could produce
      eggs here through almost all of the year. However, a massive annual reduction in
      the reproductive output of this parasite in the U.K., compared with that in
      natural sites, is predicted.

PMID- 9512995
TI  - Prevalence and risk factors associated with serum antibodies against Trichinella
      spiralis.
AB  - The presence of antibodies against Trichinella spiralis was investigated in a
      semi-rural county of Mexico using ELISA and electroimmunotransfer blot assay with
      crude larvae and ES antigens. The association of antibodies to several social,
      hygienic and dietary factors was also investigated. Antibody prevalences between
      1.0 and 1.9% were found. Risk factors associated were gender female and ingestion
      of moronga, a pork meat sausage-like product. Our results suggest the presence of
      an endemic, unnoticed form of human trichinellosis. These observations may be
      relevant for other countries, especially in rural and semi-rural areas, where
      sylvatic and domestic life-cycles of Trichinella coexist.

PMID- 9512996
TI  - Extensive intra-alveolar haemorrhage caused by disseminated strongyloidiasis.
AB  - We describe here four cases of disseminated strongyloidiasis. In Okinawa, it has
      been reported that about 10% of the residents are infected with Strongyloides
      stercoralis, but disseminated cases are rare. Detailed histopathological
      examination revealed that the present four cases could clearly be separated into
      two groups, two acute cases and two subacute cases. The acute cases died rapidly
      due to extensive diffuse intra-alveolar haemorrhage in both lungs. However, there
      were no inflammatory infiltrates, abscesses or granulomas in the lungs. Worms
      were demonstrated in the alveolar spaces. No extensive bleeding was observed in
      any organs except the lungs. The acute cases could be diagnosed as severe diffuse
      intra-alveolar haemorrhage syndrome, but deposition of immune complex (parasite
      antigen and immunoglobulins) and complement C3c was not demonstrated in the
      alveolar wall and small vessels of the lung. The subacute cases exhibited no such
      extensive haemorrhage, but scattered microabscesses were found with sepsis.
      During the migration of the worms from the colon, enteric bacteria entered the
      circulation in the two subacute cases. The acute cases received steroid therapy
      before the dissemination of the worms, but the two subacute cases did not.
      Steroids might have influenced the Strongyloides stercoralis dissemination and/or
      the course of the disease.

PMID- 9512997
TI  - Genetic evidence indicating that Cooperia surnabada and Cooperia oncophora are
      one species.
AB  - Sequences of the second internal transcribed spacer (ITS-2) of ribosomal DNA were
      determined for the trichostrongylid nematodes Cooperia surnabada and Cooperia
      oncophora, to test the hypothesis that they represent one species. Also included
      for comparison were other morphologically distinct species within the genus,
      namely Cooperia punctata and Cooperia curticei. There were no differences in the
      consensus ITS-2 sequences between C. oncophora and C. surnabada, whereas each
      taxon differed from C. punctata and C. curticei by 1.7% and 4.1%, respectively.
      Also, C. punctata differed from C. curticei by 5.0%. Based on these results and
      the DNA studies of other trichostrongylid species, it is proposed that C.
      oncophora and C. surnabada represent a single species.

PMID- 9512998
TI  - Differences in the second internal transcribed spacer of four species of
      Nematodirus (Nematoda: Molineidae).
AB  - Genetic differences among Nematodirus spathiger, Nematodirus filicollis,
      Nematodirus helvetianus and Nematodirus battus in the nucleotide sequence of the
      second internal transcribed spacer (ITS-2) of ribosomal DNA ranged from 3.9 to
      24.7%. Pairwise comparisons of their ITS-2 sequences indicated that the most
      genetically similar species were N. spathiger and N. helvetianus. N. battus was
      the most genetically distinct species, with differences ranging from 22.8 to
      24.7% with respect to the other three species. Some of the nucleotide differences
      among species provided different endonuclease restriction sites that could be
      used in restriction fragment length polymorphism studies. The ITS-2 sequence data
      may prove useful in studies of the systematics of molineid nematodes.

PMID- 9512999
TI  - Comparison of the inflammatory responses of mice infected with American and
      Australian Trichinella pseudospiralis or Trichinella spiralis.
AB  - This study was designed to determine if the Tasmanian devil isolate of
      Trichinella pseudospiralis suppressed inflammation as does the original isolate.
      While adult worm numbers were similar in all groups, lower enteritis occurred in
      devil isolate-infected mice compared with mice infected with the original isolate
      of T. pseudospiralis or with Trichinella spiralis. Diaphragm muscle inflammation
      was greater in T. spiralis-infected than in mice infected with either isolate of
      T. pseudospiralis or concurrently infected with T. spiralis and either of the
      isolates of T. pseudospiralis. Granuloma inflammation was lower in mice infected
      with either isolate of T. pseudospiralis compared with uninfected or T. spiralis
      infected mice. The devil isolate down-regulated inflammation more profoundly
      during the intestinal phase than the muscle phase compared to the original
      isolate, differences which may be related to the biology of their natural hosts.

PMID- 9513000
TI  - Evaluation of diagnostic ultrasound as a mass screening technique for the
      detection of hydatid cysts in the liver and lung of sheep and goats.
AB  - Ultrasound examination of the liver and lung followed by post-mortem examination
      was performed in 16 sheep and 284 goats. Thirty-one (10.3%) were positive for
      hydatid cysts on ultrasound examination and 46 (15.3%) were positive on post
      mortem examination. Twenty-one positive on post-mortem examination were falsely
      identified as negative on ultrasound examination. Of the 254 animals negative on
      post-mortem examination, six (2.4%) were falsely identified as positive on
      ultrasound examination. The sensitivity and specificity of ultrasound examination
      for detecting hydatid cysts in sheep and goats was 54.36% and 97.64%,
      respectively (positive predictive value: 80.64%; negative predictive value:
      92.19%).

PMID- 9513001
TI  - Modulation of migration of Oesophagostomum dentatum larvae by inhibitors and
      products of eicosanoid metabolism.
AB  - The effects of eicosanoids and of inhibitors of eicosanoid synthesis on the
      migration of third-stage larvae (L3) of Oesophagostomum dentatum were studied in
      an in vitro migration assay procedure. The L3 were incubated with
      diethylcarbamazine (DEC), indomethacin (INDO) or acetylsalicylic acid (ASA).
      Incubation with these inhibitors of eicosanoid metabolism resulted in a dose
      dependent reversible inhibition of migration. The antimigratory effect of DEC
      could be completely reversed by treatment of the L3 with the lipoxygenase (LOX)
      products leukotriene (LT) B4 or LTC4. LTD4 had a less distinct but similar
      effect, while LTE4 failed to reverse migration inhibition. Treatment with
      combinations of cyclooxygenase (COX)-products (prostaglandin, PG) partially
      restored the migration ability of ASA-treated L3, while PGD2, PGE2, PGF2 alpha or
      PGI2 exerted no distinct effect on ASA-treated L3 when given separately. The
      suppression of L3 migration by compounds that are known as antagonists of
      eicosanoid synthesis and the stimulation of migration of inhibitor-treated L3 by
      simultaneous application of eicosanoids indicate that these lipid mediators may
      play a significant role in physiological processes that interact with worm
      motility.

PMID- 9513002
TI  - The spatial organisation of the central nervous system of Mesocestoides corti as
      revealed by microinjection of carbocyanine dye.
AB  - The carbocyanine dyes DiI, DiA and DiO were microinjected into the cerebral
      ganglion of intact Mesocestoides corti tetrathyridia to determine the spatial
      organisation and connectivity patterns of the CNS. Of the dyes tested, DiI proved
      to be the most effective, giving highly fluorescent and persistent staining of
      even very fine calibre afferent and efferent nerve fibres. DiI labelling, in
      conjunction with transmission electron microscopy, revealed the nervous system to
      consist of sensory endings, directly connected to the cerebral ganglion by
      elongated cellular tracts, efferent nerve fibres which innervated the suckers,
      and longitudinal nerve cords which travelled along the remainder of the body.

PMID- 9513003
TI  - Why certification of medical software would be useful?
AB  - Human drugs and medical devices have to be approved by the health authorities
      before they can enter the market. For medical software this is not needed. The
      main argument to resist all attempts to regulate medical software has been that
      it is impossible to guarantee that software is error-free. This is true of all
      software. However, in medical software the correctness of medical knowledge is at
      least as important as the correctness of the code itself. The medical contents of
      the software could usually be evaluated but the end-users do not have the time or
      possibilities to do so. The Internet makes it possible to provide commercial
      services designed by non-professionals. For health care, there are already
      several commercial services on the net. Since there is no quality assurance or
      regulation of medical software anyone can sell medical software on the net. Even
      if physicians were cautious enough not to use untested software, there is a
      possibility that patients do. In Finland, where over 10% of the population is
      using the Internet at least weekly, the problem is real. It is impossible to
      remove poor services from the net and therefore, it is essential to guide the
      users to use high quality services. The paper discusses different aspects of
      evaluation of medical software.

PMID- 9513004
TI  - Desiderata for product labeling of medical expert systems.
AB  - The proliferation and increasing complexity of medical expert systems raise
      ethical and legal concerns about the ability of practitioners to protect their
      patients from defective or misused software. Appropriate product labeling of
      expert systems can help clinical users to understand software indications and
      limitations. Mechanisms of action and knowledge representation schema should be
      explained in layperson's terminology. User qualifications and resources available
      for acquiring the skills necessary to understand and critique the system output
      should be listed. The processes used for building and maintaining the system's
      knowledge base are key determinants of the product's quality, and should be
      carefully documented. To meet these desiderata, a printed label is insufficient.
      The authors suggest a new, more active, model of product labeling for medical
      expert systems that involves embedding 'knowledge of the knowledge base',
      creating user-specific data, and sharing global information using the Internet.

PMID- 9513005
TI  - Quantitative evaluation of clinical software, exemplified by decision support
      systems.
AB  - To ensure the correctness of publicity material ('truth in labelling') and to
      inform their licensing decisions, agencies certifying or regulating any clinical
      computer system will need information about the system's structure, performance
      and likely impact on users and the environment in which they work. This
      information must be reliable and complete, so it needs to be collected in a
      structured, rigorous evaluation programme. Clinical decision support systems are
      generally more complex and their effects less easy to predict than most other
      clinical software, so pose the greatest challenge to evaluators. They are
      therefore the focus of this paper.

PMID- 9513006
TI  - Approaches for certification of electronic prescription software.
AB  - The proper management of drug treatment is essential, since adverse drug
      reactions are common reasons of hospitalisations. Expenditure on drug therapy has
      also been growing faster than any other aspect of health care in many countries.
      Savings and quality improvements in drug treatment could be achieved with
      computerised prescribing. In this paper, the architecture of an electronic
      prescription system is described in the light of software certification and
      registration. An electronic prescription system is an example of a system
      supporting shared care and therefore it should be person based, integrated,
      secure and confidential and data should be shared among health care institutions.
      The system architecture shares the idea of a virtual patient record and a smart
      card will be used as a key to prescription data located on the network. The
      certification and registration of medical software is a difficult and costly
      procedure. Ensuring the quality of software can be based on; certification of
      development process, voluntary evaluation, and post-market surveillance.
      Voluntary evaluation practice would be a precious tool for both the customers and
      software developers, and it would also be an invaluable source of information in
      terms of developing new software.

PMID- 9513007
TI  - Investigation of filter sets for supervised pixel classification of cephalometric
      landmarks by spatial spectroscopy.
AB  - The diagnostic process of orthodontics requires the analysis of a cephalometric
      radiograph. Image landmarks on this two-dimensional lateral projection image of
      the patient's head are manually identified and spatial relationships are
      evaluated. This method is very time consuming. A reliable method for automatic
      computer landmark identification does not exist. Spatial Spectroscopy is a
      proposed method of automatic landmark identification on cephalometric
      radiographs, that decomposes an image by convolving it with a set of filters
      followed by a statistical decision process. The purpose of this paper is to
      discuss and test appropriate filter sets for the application of Spatial
      Spectroscopy for automatic identification of cephalometric radiographic
      landmarks. This study evaluated two different filter sets with 15 landmarks on
      fourteen images. Spatial Spectroscopy was able to consistently locate landmarks
      on all 14 cephalometric radiographs tested. The mean landmark identification
      error of 0.841 +/- 1.253 pixels for a Multiscale Derivative filter set and 0.912
      +/- 1.364 pixels for an Offset Gaussian filter set was not significantly
      different. Furthermore, there were no significant differences between
      identification of individual landmarks for the Multiscale Derivative and the
      Offset Gaussian filter set (P > 0.05). These results suggest that Spatial
      Spectroscopy may be useful in landmark identification tasks.

PMID- 9513009
TI  - Educational section.

PMID- 9513008
TI  - SUTIL: intelligent ischemia monitoring system.
AB  - SUTIL is an intelligent monitoring system for intensive and exhaustive follow up
      of patients in coronary care units. This system processes electrocardiographic
      and hemodynamic signals in real time, with the main objective of detecting
      ischemic episodes. In this paper, we describe the tasks included in SUTIL. In
      addition to basic tasks, those at higher levels will also be presented. Some of
      these latter tasks attempt to mimic, to some extent, the way in which the human
      expert operates.

PMID- 9513010
TI  - The intuition of the negative in Playing and reality.
AB  - The author draws some parallels between his own conceptions on the work of the
      negative with some ideas presented by Winnicott in the ultimate version of his
      paper on 'Transitional objects and transitional phenomena'. He underlines the
      germs of the intuition of the negative in Winnicott's general theory ('not me
      possession', transitional object as not being the breast, the decathexis of the
      representation of the object). He then goes on to examine in detail the clinical
      material of a patient, in the last part of the paper, which has been published
      posthumously. In this last part the negative is mentioned explicitly and the idea
      is openly presented. We have here a concept of which Winnicott had the intuition
      without having the possibility of considering its full development and
      implications. It so happened that the patient whose clinical material is
      published in 'Playing and Reality' came to the author to continue her analytic
      experience. One can compare the material presented in these two analytical
      relationships. The author comments about his relationship with the patient and of
      the way she meets his own hypotheses.

PMID- 9513011
TI  - From instinct to self: the evolution and implications of W. R. D. Fairbairn's
      theory of object relations.
AB  - The authors argue that fifty years after the initial publication of W. R. D.
      Fairbairn's object-relations theory of the personality, his ideas have moved to
      the centre of psychoanalysis and provide the most cogent theoretical rationale
      for many modern concepts of technique and the therapeutic action of
      psychoanalysis. In particular, Fairbairn centred object-relations theory on the
      person's need for relationships from infancy and throughout life, and gave the
      first detailed description of the sequential processes of internalisation of the
      rejecting object, followed by splitting of the ego and repression of painful
      internal object relations. He described the way these processes led to the
      organisation of the ego as an internal system of subegos and part objects (which
      are actually organisations of the ego, too) which are always in dynamic
      interaction with each other and which determine the quality of external
      relationships. This paper draws on Fairbairn's early writings, many of them
      recently published for the first time, to describe the origin of Fairbairn's
      ideas in his study of philosophy, to outline his theory of object relations, and
      to consider current developments and applications of these ideas in
      psychoanalysis and beyond.

PMID- 9513012
TI  - Disclosures and refutations: clinical psychoanalysis as a logic of enquiry.
AB  - The author argues that the empirical status of psychoanalysis has been distorted
      by the controversy surrounding Aristotelian and Galilean-Newtonian schemes of
      science, whose core ideas, respectively, are scientific concepts or forms and
      scientific laws. Bound by the Euclidian axiomatic tradition, Newtonian-style
      'laws' do not obtain in the social sciences, and in biology they apply only at
      near-molecular levels, not at the level of mind. Continuing the traditional
      Aristotelian reliance on 'exemplars', neither Freud's nor Darwin's work fits the
      deductivist, infallibilistic scientific criteria used by philosophers such as
      Tarski, Popper or Grunbaum. Rebutting the charge that the workings of
      psychoanalysis are not explicit enough, this paper unfolds the logic of enquiry
      it utilises. In contrast to Newtonian inductivism, Popper's method of conjectures
      and refutations and Lakatos's method of proofs and refutations, clinical
      psychoanalysis employs a 'practical logic' of disclosures and refutations, a
      constantly evolving enquiry of multi-layered and tentative evidence of
      discordance and analogy. Such epistemic fallibilism, relying on a build-up of
      ostensive evidences rather than on 'certainties', is illustrated in the text by
      Moore's famous 'two-hands' argument, is held to fit in with the workings of
      everyday discernment and, arguably, with Darwinian evolution.

PMID- 9513013
TI  - A matrix of hysteria.
AB  - The psychoanalytic literature of the last decades on hysteria is reviewed and its
      overemphasis on pre-oedipal concepts is demonstrated. A matrix of hysteria, which
      is a contemporary re-reading of Freud's basic conceptualisation, is presented. It
      integrates oedipal concepts with others borrowed from object-relations theories,
      self-psychology and the intersubjective approach. In this way the focus on the
      issues of gender and sexuality in hysteria is continued, without the original
      roots being lost. The focus is on the content, and the structure may vary. Within
      the first axis of the matrix, the author proposes to identify the conflict of
      gender and sexual identity as the unconscious and conscious solutions that a
      hysteric adopts to the question 'am I a man or a woman?' In an attempt to
      identify hysteria's particular psychic dynamics, a range of concepts is
      suggested. Repression and conversion are incorporated to constitute the second
      and third axes of the matrix. Repression, denial, dissociation and fantasy are
      shown to be employed in the context of gender and sexuality and along a continuum
      of personality structures. In this context, the turning to the body, the
      conversion, still acts as an effective language, to which we have to listen.

PMID- 9513014
TI  - Modes of therapeutic action.
AB  - The dialectic in psychoanalysis between theories about the mutative effects of
      interpretation and psychological knowledge and those concerning the effects of
      interpersonal interaction constitutes an important tension for approaches to
      psychoanalytic technique. This essay briefly summarises the thinking around these
      alternative conceptualisations of therapeutic action, and introduces a new
      empirically derived model, that of 'repetitive interaction structure', which
      attempts to bridge therapeutic action by insight and by relationship. Interaction
      structure is a way of formulating those aspects of the analytic process that have
      come to be termed intersubjectivity, transference-countertransference enactments
      and role responsiveness. The concept operationalises important aspects of
      interpersonal interaction, and can help specify the two-person patterns that
      emerge in an analysis. Patient and analyst interact in repetitive ways; these
      patterns of interaction, which are slow to change, probably reflect the
      psychological structure of both patient and analyst, whether psychic structure is
      conceptualised in terms of object-representations or compromise formations and
      impulse-defence configurations. Therapeutic action is located in the experience,
      recognition and understanding by patient and analyst of these repetitive
      interactions. Interaction structures stress the importance of the intrapsychic as
      a basis for what becomes manifest in the interactive field. Clinical
      illustrations from a psychoanalysis are provided, and research on repetitive
      interaction structures is described.

PMID- 9513015
TI  - Vicissitudes of remembering in the countertransference. Fervent failure,
      colonisation and remembering otherwise.
AB  - The author argues that certain kinds of transference can have great impact on the
      analyst's ego functioning. One such effect is impairment of ready recall of the
      analytic material, such as life historical data, the analytic process itself, and
      his or her role as analyst. The analyst strives to remember otherwise by
      analysing the patient's projective identifications and other defensive,
      manipulative strategies. When successful, these strategies may be said to
      colonise the analyst's mind. Although other ego functions are often affected by
      colonisation, remembering is of particular interest owing to its importance in
      building up and keeping ready at hand the contexts within which balanced and
      timely interpretations can be formulated with some hope that they will be heard
      and used effectively and progressively by the threatened, phantasy-ridden
      patient. Special attention will be paid to themes of failure; other themes, such
      as omnipotence and erotised transferences will be considered later on. Clinical
      illustrations are included.

PMID- 9513016
TI  - Historicising the origins of Kleinian psychoanalysis. Klein's analytic and
      patronal relationships with Ferenczi, Abraham and Jones, 1914-1927.
AB  - Historical examination of Klein's clinical synthesis through three crucial
      analytic relationships enables the author to account for the way in which the
      cultural background--gender, politics and textual analysis--informs theory
      formation. Klein's analysis with Ferenczi led to her work with children and self
      analysis. With Abraham, she arrived at ideas about the origins of neurosis,
      linking severely disturbed with infantile states of mind. The author argues that
      the role of the cultural background must be explicated since Klein's initial
      clinical cohort existed in a Germany ravaged by starvation and absent fathers,
      which figured in the distinctive significance of the mother-child relationship.
      Klein's play technique involving toys understood it as the exteriorisation of the
      child's fantasy life, leading to fresh hypotheses about the early child. By 1925,
      her work collided with the interests of Sigmund and Anna Freud, who were in the
      throes of a succession crisis. It was imperative to establish Anna as the new
      'pre-eminent' Freud, leading to hasty publication and direct critique of Klein's
      child technique. Through the intercession of Ernest Jones, who provided her with
      much needed support by 1927, the first shots of the Freud-Klein controversy were
      fired when Klein, propelled to centre stage in the international movement,
      established her reputation in London.

PMID- 9513017
TI  - Clinical experience with psychoanalytic post-termination meetings.
AB  - The authors describe post-termination meetings in order to examine the
      controversial issue of the proper relationship between analyst and patient at
      this stage. In the first case the meetings facilitated the patient's re-entering
      treatment, leading to significant further growth. In the second and third cases,
      the meetings re-ignited mourning for the analyst and furthered analytic gains.
      The authors' overall impression was that the post-termination contacts were
      helpful for all three patients. Their limited data contradicted the long-standing
      assumption that all post-termination contact, unless specified as a course of
      further treatment, is harmful to the patient. The authors suggest that such
      meetings stabilise analytic gains, provide a joint assessment of analytic outcome
      from a useful later perspective and provide an opportunity for further analytic
      work. The consideration of any post-termination changes in the patient allows for
      a more inclusive evaluation of the analysis than was possible earlier. While
      acknowledging the need to consider such meetings thoughtfully in order to avoid
      any harmful enactment of wishes by the patient or the analyst, the authors
      encourage analysts to explore and report such meetings to replace unexamined
      assumptions and develop a body of clinical data about the effects of post
      termination contacts.

PMID- 9513018
TI  - Splitting and the psychodynamics of adolescent and young adult suicide attempts.
AB  - The authors point to a link between the contradictory meanings and functions of
      adolescent and young adult suicide attempts and splitting mechanisms that may
      explain the normal coexistence of opposite tendencies. They argue that suicide
      attempts of young people reveal a deadlock in development, in which individuation
      and the need for dependence are equally intolerable because of the arousal of
      anxiety linked to persecution or abandonment. The sexualisation of the body and
      of intimate relationships engenders a risk of psychic decompensation, which is
      temporarily set aside through the reinforcement of splitting and denial; the
      suicide attempt, however, is precipitated by conditions that provoke a traumatic
      return of that which has been split-off and denied. Suicide attempts thus
      represent an act of compromise, the object of which is to avoid psychic
      disorganisation through the re-establishment of a precarious equilibrium between
      antithetical tendencies that splitting can simultaneously address. In particular,
      suicide may represent an attempt at individuation and flight from incest while at
      that same time satisfying fusion needs and the realisation of oedipal fantasies.
      Clinical examples are presented to illustrate the manifestation and the function
      of splitting in young people's suicide attempts.

PMID- 9513019
TI  - Interaction and transference.

PMID- 9513020
TI  - Is the transference feared by the psychoanalyst?

PMID- 9513021
TI  - Response to Kenneth Eisold.

PMID- 9513022
TI  - Towards a clinically and empirically sound theory of motivation.

PMID- 9513023
TI  - A reconsideration of objectivity in the analyst.

PMID- 9513024
TI  - Memory: brain systems that link past, present and future.

PMID- 9513025
TI  - Susceptibility genetics in the etiopathogenesis of Alzheimer's disease: role for
      potential confounding factors.

PMID- 9513026
TI  - Lessons from mixed dementia.

PMID- 9513027
TI  - 1997 IPA/Bayer Research Awards in Psychogeriatrics. Subcortical hyperintensities
      in late-life depression: acute response to treatment and neuropsychological
      impairment.
AB  - Subcortical hyperintensities are easily visualized areas of signal abnormality
      that are seen on T2-weighted magnetic resonance imaging (MRI). Characteristically
      they occur in the white matter of the brain and are more common in elderly
      people. In depression, little is known of the clinical significance of
      subcortical hyperintensities or their contribution to the prognosis. Fifty-eight
      consecutive patients with DSM-III-R depression and an age range of 65 to 85 years
      were prospectively collected from an old-age psychiatry service. Response to
      treatment was assessed with a clinical global outcome measure. A neuropsychology
      battery was completed on all patients after treatment. Forty-four patients
      completed MRI scanning. The scans were scored using a regional rating system for
      hyperintensities. Forty-eight percent of patients had a favorable response to
      treatment on the clinical global outcome scale. Poor outcome was associated with
      female sex (p = .07), poor physical health (p = .040), diabetes (p = .018),
      psychosis (p = .026), and an early age at onset of first episode of depression (p
      = .036). Even after adjustment for confounding effects, there were significant
      neuropsychological associations with the regional hyperintensities. Distribution
      in the periventricular area correlated with delayed recall after distraction (p =
      .025), and punctate lesions in the basal ganglia correlated with impaired
      category production (p = .020). Pontine reticular formation hyperintensities were
      related to impaired psychomotor speed (p = .04). Location in the frontal deep
      white matter (p = .024), basal ganglia (p = .03), and pontine reticular formation
      (p = .02) was associated with a poor acute response to treatment. However, the
      response to treatment was not related to total cerebral white-matter
      hyperintensity load. A logistic regression equation included all the significant
      prognostic features and found four independent predictors of poor outcome: More
      than five punctate lesions of the basal ganglia, diabetes, lower mean arterial
      pressure, and hyperintensity of the pontine reticular formation significantly
      predicted outcome. These four factors correctly predicted 95.6% of patients with
      a poor outcome and 85.7% with a favorable outcome. In late-life depression,
      subcortical hyperintensities are common. Lesions in the cerebral white matter are
      predominantly associated with memory disturbance, and those in deeper
      infratentorial areas, with psychomotor slowing and executive deficits. Total
      white-matter load has no prognostic value, and although some subcortical regions
      are associated with poor response, individually they have little specificity.
      However, a combination of involvement in three areas (basal ganglia, pons, and
      frontal lobe) is clinically relevant and predicts outcome with great accuracy
      (91%). Patients with lesions in the basal ganglia and deep white matter had an
      especially poor response to pharmacotherapy.

PMID- 9513028
TI  - 1997 IPA/Bayer Research Awards in Psychogeriatrics. Associations between
      dysfunctional behaviors, gender, and burden in spousal caregivers of cognitively
      impaired older adults.
AB  - Reductions in healthcare spending and current demographic trends will result in
      increasing demands to care for aging relatives, especially those with cognitive
      impairment (e.g., Alzheimer's disease). Taking care of older individuals with
      cognitive impairment can be very challenging and burdensome. Caregiver burden is
      associated with negative outcomes such as caregiver depression and increased
      likelihood of patient institutionalization. One hundred eleven patients and their
      spousal caregivers were studied using a pre-post design. All subjects received a
      comprehensive medical intervention that included medical management of patients'
      problems and education of caregivers. We examined changes in patients' function
      and caregiver burden. At follow-up, patients' cognition and independence in
      activities of daily living had continued to deteriorate whereas their mood was
      improved. Regression analyses showed that changes in caregiver burden were
      positively associated with changes in the frequency of dysfunctional behaviors
      but not with changes in cognition. Gender was also related to changes in
      caregiver burden; male caregivers were more likely than female caregivers to
      report reductions in burden at follow-up. These data suggest medical
      interventions may provide some relief to caregivers of cognitively impaired older
      patients, but more research is required to identify the causal agents of this
      effect.

PMID- 9513029
TI  - 1997 IPA/Bayer Research Awards in Psychogeriatrics. The wish to die in very old
      persons near the end of life: a psychiatric problem? Results from the Berlin
      Aging Study.
AB  - The wish to die in elderly persons is currently under debate. Experts are
      questioning whether it is natural for these individuals to show a wish to die,
      whether the right to eventually kill oneself should be respected, or whether
      suicidal intentions in old age are expressions of mental disorders that need
      intensive, professional care. A representative community sample of 516 persons
      aged 70 to 105 was extensively investigated by psychiatrists using the structured
      interview Geriatric Mental State Examination-Version A (GMS-A) and several self
      rating and observer-rating scales. Diagnoses were made according to DSM-III-R
      criteria and by clinical judgment. The goal of the study was to find examples of
      "pathology-free wishes to kill oneself." A total of 115 out of 516 very old (70
      to 105 years) persons, which represents 21.1% of the community population, said
      at the time of investigation that they wanted to die or felt life was not worth
      living (Hamilton Depression Rating Scale [HAMD] score 1, 2, or 3). Forty-three
      very old persons (6% of the community population) had the wish to be dead
      according to the HAMD or the GMS-A, and 11 persons (2% of the community
      population) had suicidal intentions. Depending on the intensity of suicidality,
      80% to 100% were clinically diagnosed as having psychiatric disorders and half to
      three quarters showed symptoms fulfilling the criteria of at least one specified
      psychiatric diagnosis. Acute suicidal intentions were in all cases associated
      with at least one specified diagnosis according to DSM-III-R. Thirteen persons
      out of 54 who actually wanted to die (GMS-A category 4, 5, 6 or HAMD category 2,
      3) did not fulfill criteria for specified diagnoses. Seven individuals showed
      scores in self-rating and observer-rating scales that speak for mental disorders
      apart from pure suicidality. Six remaining persons are described in greater
      detail in short case vignettes. They showed either mild but chronic psychiatric
      disorders, fluctuating courses, or an atypical phenomenology of psychiatric
      disorders. The results of this study strongly suggest that the wish to be dead in
      the very old is most probable, and suicidal intentions are definitely associated
      with psychiatric disorders.

PMID- 9513031
TI  - Risk factors for clinically diagnosed Alzheimer's disease: a case-control study
      of a Greek population.
AB  - Many efforts have been made to trace the causes of Alzheimer's disease (AD).
      There are, however, many points of controversy among reports from the same
      country as well as among reports from different countries. The current study is a
      case-control study to determine the risk factors in the development of AD in
      Greece. Sixty-five patients with AD and 69 age-matched controls were examined.
      All patients with AD fulfilled the DSM-IV criteria for AD and NINCDS-ADRDA
      criteria for probable AD. Demographic characteristics such as gender, current
      marital status, who he/she is living with, education, main place of residence in
      childhood, adulthood, and late life, occupational hazards, patient's medical
      history (history of diabetes mellitus and hypertension), life habits like alcohol
      consumption and smoking, and a history of head trauma, heart attack, stroke,
      parkinsonism, or depression were collected from the subject or from an informant.
      A family history of selected diseases (hypertension, diabetes mellitus, dementia,
      Parkinson's disease, Down's syndrome, stroke) was also elicited. Ages of father
      and mother at birth were also recorded. Chi-square test, Kruskal-Wallis analysis
      of variance, cluster analysis, and logistic regression analysis were used for
      statistical analysis. The results (chi-square test) showed a statistically
      significant difference between patients with dementia of the Alzheimer type and
      controls as far as marital status (p = .04), the subject's history of major
      depressive episode (p = .02), and family history of dementia (p = .002) were
      concerned. Logistic regression analysis results produced a complex model of
      family aggregation of dementia, with patients with a history of depression and
      family history of dementia having an up to seven times higher risk of developing
      AD. These findings, especially a family history of dementia, are consistent with
      most of the literature.

PMID- 9513030
TI  - Impact of anesthesia on the cognitive functioning of the elderly.
AB  - Exposure to general anesthesia has been suggested as a possible cause of long
      term cognitive impairment in elderly subjects. The present study reviews the
      literature in this field in order to describe postoperative cognitive impairment
      in elderly populations, to determine to what extent this may be attributed to
      anesthetic agents, and to consider evidence of a causal relationship between
      anesthesia and onset of senile dementia. A systematic literature search was
      conducted using five bibliographic databases (PASCAL, Medline, Excerpta Medica,
      Psychological Abstracts, and Science Citation Index). Significant cognitive
      dysfunction was found to be common in elderly persons 1 to 3 days after surgery,
      but reports of longer-term impairment are inconsistent due to the heterogeneity
      of the procedures used and populations targeted in such studies. Incidence rates
      vary widely according to type of surgery, suggesting that factors other than
      anesthesia explain a significant proportion of the observed variance. Anesthesia
      appears to be associated with longerterm cognitive disorder and the acceleration
      of senile dementia, but only in a small number of cases, suggesting the existence
      of other interacting etiological factors.

PMID- 9513032
TI  - Short-term course of mental illness in middle age and late life.
AB  - The heterogeneity in severe mental illnesses means that although some persons
      exhibit a chronic course in later life, others may recover for long periods or
      have episodes throughout the lifespan. The challenge to mental health providers
      is to identify those people most at risk for a chronic or relapsing course in
      later life. Data described here come from a prospective study of course and
      adjustment in severe mental illness for persons over age 40. The sample of 313
      people, residing in the community and both in treatment and not in treatment, is
      unique. Six 8-month course patterns were identified; nearly one third of the
      participants had course patterns that were unstable, and one third were well
      across the 8 months. Older participants were more stable and less depressed, but
      otherwise were very similar to those in middle age. Demographic and history
      variables that predict long-term outcomes were not useful for predicting short
      term recovery or relapse.

PMID- 9513033
TI  - Depression measured by the Zung Depression Status Inventory is very rare in a
      Finnish population aged 85 years and over.
AB  - The purpose of this study was to obtain information about the prevalence of
      depressive symptoms in a representative sample of elderly subjects aged 85 years
      and over. The study was carried out as a population-based interview study in the
      City of Vantaa in Finland. The Zung Depression Status Inventory (DSI) was used to
      evaluate various depressive symptoms in this study population. The DSI scores
      range from 20 to 80; the higher the score, the more severe the disturbance. In
      subjects interviewed (n = 467, 362 women, 105 men), the prevalence estimates of
      depression with cutoff scores used in earlier studies (40 and 48) were very low:
      5.2% and 1.1%. Also, the mean DSI score (SD) was very low, 27.9 (6.4). The scores
      tended to decrease with age, although the differences were not statistically
      significant. The DSI means were 28.0 (6.1) for women and 27.3 (7.2) for men (p =
      .0349). Women had a greater risk of being classified as depressed on the DSI
      (odds ratio: 1.60, 95% confidence interval: 1.00-2.57, p = .049). Feelings of
      emptiness, personal devaluation, and depressive mood were the most common
      depressive symptoms. In conclusion, the present population-based study shows that
      subjective experience of depression is very rare in Finnish people aged 85+. Our
      results suggest that optimistic mood might give some protection against death.

PMID- 9513034
TI  - [Influence of wall thickness on asynergy during exercise two-dimensional
      echocardiography in patients with old myocardial infarction].
AB  - The relationship between left ventricular wall motion worsening (new asynergy;
      newly developed or worsened asynergy) in the affected part of old myocardial
      infarction during exercise two-dimensional echocardiography and the wall
      thickness at diastole was evaluated in 20 patients with more than 51% diameter
      stenosis in only the infarcted related artery using symptom-limited graded supine
      bicycle exercise test and two-dimensional echocardiography. End-diastolic wall
      thickness at normal part of the wall (WtdN) and infarcted parts (WtdI) on the
      parasternal short-axis view at the papillary muscle level at rest were measured
      and the wall thickness ratio, WtdI/WtdN x 100(%), was calculated. The rate
      pressure product at the time when new asynergy appeared and the appearance time
      of new asynergy after starting exercise were measured in seconds. Mean values for
      the 20 patients were wall thickness ratio of 75.7 +/- 10.0% (mean +/- SD), new
      asynergy appearance time of 219 +/- 116 sec after exercise and rate pressure
      product of 14,209 +/- 2,997 mmHg. beat/min. Smaller wall thickness ratio was
      associated with lower rate pressure product levels (r = 0.696, p < 0.01) and
      shorter appearance time of new asynergy (r = 0.772, p < 0.01). There was no
      significant correlation between the percentage diameter stenosis of the infarct
      related artery and appearance time of new asynergy or rate pressure product. New
      asynergy appeared at a specific infarcted part of the wall, and thinner walls
      were associated with shorter appearance time of new asynergy with lower rate
      pressure product levels, regardless of the severity of stenosis of the infarct
      related artery.

PMID- 9513035
TI  - [Early result of volume reduction left ventriculoplasty (Batista operation) for
      dilated cardiomyopathy].
AB  - The Batista operation is intended to improve cardiac function by reducing the
      diameter of the left ventricle by excising of a sizable amount of the left
      ventricular free wall. Candidates for this operation are patients awaiting
      cardiac transplantation due to end-stage dilated cardiomyopathy and those
      unsuitable for transplantation because of age, physical or economical reasons. We
      performed this operation in 10 patients between December 1996 and October 1997.
      The baseline indication is left ventricular diastolic dimension > or = 70 mm and
      New York Heart Association (NYHA) class III or IV. There were eight men and two
      women aged from 16 to 60 years (mean 46 years). All had non-ischemic
      cardiomyopathy including seven idiopathic and one each of hypertrophic,
      arrhythmogenic right ventricular and valvular (sarcoidosis) cardiomyopathy. Eight
      patients were in NYHA class IV and six needed inotropic drip therapy prior to the
      operation. Nine patients had significant mitral regurgitation and six had
      tricuspid insufficiency concomitantly. Eight patients underwent mitral valve
      replacement and one was treated with mitral valve plasty. Six patients also had
      tricuspid plasty combined with partial left ventriculectomy. Eight patients
      survived. Mean value of left ventricular end-diastolic diameter was reduced from
      77.8 mm to 59.8 mm, left ventricular end-diastolic volume index was reduced from
      189.3 to 99.2 ml/m2, ejection fraction was increased from 19.0% to 33.8% and NYHA
      class improved from 3.8 to 1.8. Six months later, left ventricular dilatation was
      not noticed in four patients examined. The Batista operation offers real hope for
      patients with end-stage dilated cardiomyopathy, but we still have much to learn.

PMID- 9513036
TI  - [Unclassified cardiomyopathies: subspecies and their transformation].
AB  - Some cases with hypertrophic cardiomyopathy (HCM) progress to dilated
      cardiomyopathy (DCM), therefore, we hypothesized that a transforming-type phase
      between HCM and DCM could exist. This study was made based on a retrospective
      analysis of 471 of 1,388 patients with cardiomyopathy who underwent diagnostic
      myocardial biopsy in several hospitals between 1977 to 1995, and who were not
      diagnosed with restrictive cardiomyopathy, arrhythmogenic right ventricular
      dysplasia, specific heart muscle diseases, or electrical disturbance type of
      heart muscle diseases. Based on echocardiographic measurements, the 471 patients
      were classified into eight subgroups according to the presence or absence of
      three parameters. A: left ventricular hypertrophy (septal or posterior wall
      thickness > 12 mm), B: left ventricular dilation (left ventricular end-diastolic
      dimension > 55 mm), C: systolic dysfunction (left ventricular ejection fraction <
      50%), is signified by plus or minus ([ABC]). HCM, DCM and normal heart are
      defined as [+(-)-], [-(+2)] and [-(-)-], respectively. Unclassified
      cardiomyopathy (UCM) was indicated as cardiomyopathy not diagnosed as HCM or DCM.
      Therefore, unclassified cardiomyopathies are signified as either [+2-], [+(-)+],
      [+3], [-(+)-] or [-(-)+]. Patients in each subgroup of UCM were followed up for
      6.4 +/- 6.0 years and their clinical courses compared with the histological
      findings. Of the 471 patients, 111 (24%) were classified as UCM, 240 as HCM, and
      120 as DCM. Severe myocardial disarray was noted more frequently in UCM [17 of
      111 cases (15%)] than in DCM [7 of 120 cases (6%)] (p < 0.05), and not
      significantly higher than in HCM [34 of 240 cases (14%)]. Patients with UCM whose
      conditions deteriorated had positive pathological findings (15 of 26 cases) more
      often than those without deterioration (8 of 29 cases; p < 0.05). UCM could be a
      transforming type of cardiomyopathy for some patients with HCM who progress to
      DCM. In addition, there may be a positive correlation between the histopathologic
      findings and the clinical course.

PMID- 9513037
TI  - [Intrapulmonary arterial injection of Albunex for left heart contrast
      echocardiography].
AB  - Contrast enhancement of the left heart cavity and myocardium were assessed after
      venous injection of the ultrasound contrast agent Albunex. Myocardial perfusion
      was also assessed using a drug stress and image analyzing system. The study
      population consisted of 46 patients with normal cardiac function and without
      coronary artery disease, and 38 patients with effort angina. Contrast
      echocardiography was performed by imaging the parasternal or apical long-axis
      view during pulmonary arterial injection of Albunex through a Swan-Ganz catheter.
      Contrast enhancement in the left ventricular cavity and ascending aorta were
      visually assessed. Hemodynamic, arterial blood gas and electrocardiography
      changes were recorded before and after the injection of Albunex. Contrast
      echocardiography was performed before and during intravenous infusion of
      dipyridamole to assess left ventricular myocardial enhancement by both visual
      inspection and peak background-subtracted gray level using an image analyzing
      system. Doppler flow signal change after the injection of Albunex was assessed in
      26 patients using a Doppler guide wire located in the left anterior descending
      coronary artery. Good contrast enhancement was obtained in all patients in the
      left ventricular cavity and in 17% of patients in the ascending aorta. No
      significant changes were observed in hemodynamics, electrocardiograms and aortic
      gas analysis. Significant myocardial enhancement was not seen in any patient but
      gray level analysis of the echo images during dipyridamole infusion showed
      significant enhancement in 25% of the patients without coronary artery disease
      and in 34% of the patients with effort angina. Doppler flow signal in the
      coronary artery was significantly augmented in all patients after injection of
      Albunex and suggests that ultrasound contrast agent reaches coronary arteries in
      all patients regardless of myocardial contrast enhancement. Contrast
      echocardiography with pulmonary arterial injection of Albunex is safe and useful
      to obtain sufficient left ventricular contrast enhancement. For myocardial
      perfusion assessment, further refinement of the ultrasound contrast agent and
      echo equipment is necessary.

PMID- 9513039
TI  - [Evidence-based pharmacological therapy of ischemic heart disease: with reference
      to the long-term prognosis].
AB  - Scientists verified facts. Physicians are also scientists, and should act in
      accordance with the verified facts. Considering the issue of therapeutic agents,
      medication should be based on drugs with proven efficacy for the treatment
      required, i.e., evidence-based medicine. Consideration of pharmacotherapy of
      ischemic heart disease in Japan from the aspect of improvement of long-term
      prognosis shows that calcium antagonists and nitrates, for which there is no
      evidence of improved long-term mortality, are commonly prescribed, whereas the
      use of beta-blockers, for which there is clear evidence of improvement, lags well
      behind Western countries. In the 1980s, when the efficacy of beta-blockers was
      proven in Western countries, calcium antagonists first appeared. Of course both
      patients and physicians tended to use these antagonists because of the excellent
      effects. Possibly the continuous marketing of new calcium antagonists has led to
      negative attitudes among physicians toward beta-blockers. In Japan close
      attention has never been paid to the FDA's advisory notice about nitrates issued
      in 1993. When a drug proves effective, then it becomes widely used. However, if a
      report demonstrates no efficacy of a drug, such evidence is not widely publicized
      in Japan even if the trial was internationally approved such as GISSI-3 (Gruppo
      Italiano per lo Studio della Sopravvivenza nell'Infarto miocardico) and ISIS-4
      (Fourth International Study of Infarct Survival). We should learn from the number
      of excellent megatrials conducted in Western countries. In treating patients,
      drugs with evidence of verified efficacy from those megatrials should be
      selected. The problems we have experienced with the short-acting calcium
      antagonists and Cardiac Arrhythmia Suppression Trial (CAST) studies must not be
      repeated.

PMID- 9513038
TI  - [Evaluation of cardiac function by various cardiac imaging techniques in
      mitochondrial cardiomyopathy: a case report].
AB  - A 39-year-old man with cardiomyopathy due to point mutation of mitochondrial
      DNA(3243) was admitted to our hospital because of exertional dyspnea accompanied
      by hearing disturbance and diabetes mellitus. Echocardiography revealed
      asymmetric hypertrophy of the anterolateral and posterior walls and systolic
      dysfunction of the left ventricle (fractional shortening = 18%). Pulsed Doppler
      mitral inflow velocity wave showed a pseudonormalized pattern. Iodine-123
      betamethyl-p-iodophenyl-pentadecanoic acid (123I-BMIPP) myocardial scintigraphy
      showed decreased accumulation in the anterolateral, posterior, and apical walls.
      Left ventriculography showed moderately decreased ejection fraction (43%), and
      left ventricular end-diastolic pressure was mildly elevated (18 mmHg).
      Angiography showed normal coronary arteries, but coronary flow reserve measured
      by administering intravenous adenosine triphosphate was impaired in the left
      anterior descending and left circumflex arteries compared to the right coronary
      artery. Intracellular accumulations of abnormal mitochondria were detected by
      histologic examination of the cardiac and skeletal muscles. Evaluation of cardiac
      function showed that the area of myocardial hypertrophy was nearly consistent
      with the region of decrease in 123I-BMIPP accumulation and coronary flow reserve.

PMID- 9513040
TI  - [Complete absence of iodine-123 betamethyl-p-iodophenyl-pentadecanoic acid uptake
      in patients with suspected coronary artery disease].

PMID- 9513041
TI  - L7 protein is a coregulator of vitamin D receptor-retinoid X receptor-mediated
      transactivation.
AB  - The vitamin D receptor (VDR) heterodimerizes with the retinoid X receptor (RXR)
      and requires additional protein-protein interactions to regulate the expression
      of target genes. Using the yeast two-hybrid system, we identified the previously
      described protein L7, that specifically interacted with the VDR in the presence
      of vitamin D. Deletion analysis indicated, that the N-terminus of L7, which
      harbours a basic region leucine zipper like domain, mediated interaction with the
      VDR. Binding assays with purified GST-L7 demonstrated, that L7 specifically
      pulled down the VDR, that was either expressed in yeast or endogenously contained
      in the cell line U937. Interestingly, L7 inhibited ligand-dependent VDR-RXR
      heterodimerization, when constitutively expressed in yeast. We also demonstrate
      that L7 repressed binding of VDR-RXR heterodimers to a vitamin D response
      element. Surprisingly, L7 recruited RXR to the same response element in the
      presence of 9-cis retinoic acid. Ligand-dependent protein-protein interaction in
      the yeast two-hybrid system confirmed, that binding of L7 also was targeted at
      the RXR. Our data suggest, that protein L7 is a coregulator of VDR-RXR mediated
      transactivation of genes, that modulates transcriptional activity by interfering
      with binding of the receptors to genomic enhancer elements.

PMID- 9513043
TI  - Interleukin-1 beta induction of c-fos and collagenase expression in articular
      chondrocytes: involvement of reactive oxygen species.
AB  - Interleukin-1 beta (IL-1) is implicated in cartilage destruction in arthritis
      through promotion of matrix metalloproteinase production. Upregulation of
      collagenase gene expression by IL-1 is known to require the transactivators Fos
      and Jun. Recently, reactive oxygen species (ROS) have been suggested to act as
      intracellular signaling molecules mediating the biological effects of cytokines.
      Here, we demonstrated ROS production by IL-1-stimulated bovine chondrocytes and
      that neutralizing ROS activity by the potent antioxidant, N-acetylcysteine, or
      inhibiting endogenous ROS production by diphenyleneiodonium (DPI), significantly
      attenuated IL-1-induced c-fos and collagenase gene expression. The inhibitory
      effect of DPI implicates enzymes such as NADPH oxidase in the endogenous
      production of ROS. Chondrocytes were also found to produce nitric oxide (NO) upon
      IL-1 stimulation. That NO may mediate part of the inducing effects of IL-1 was
      supported by the observation that L-NG-monomethylarginine, a NO synthase
      inhibitor, partially inhibited IL-1-regulated collagenase expression. Moreover,
      treatment of chondrocytes with the NO-producing agent, S-nitroso-N
      acetylpenicillamine, was sufficient to induce collagenase mRNA levels. In
      summary, our results suggest that ROS released in response to IL-1 may function
      as second messengers transducing extracellular stimuli to their targets in the
      nucleus, leading to augmentation of gene expression.

PMID- 9513042
TI  - DNA loop anchorage region colocalizes with the replication origin located
      downstream to the human gene encoding lamin B2.
AB  - The recently developed procedure of topoisomerase II-mediated DNA loop excision
      has been used to analyze the topological organization of a human genome fragment
      containing the gene encoding lamin B2 and the ppv1 gene. A 3.5 kb long DNA loop
      anchorage/topoisomerase II cleavage region was found within the area under study.
      This region includes the end of the lamin B2 coding unit and an intergenic region
      where an origin of DNA replication was previously found. These observations
      further corroborate the hypothesis that DNA replication origins are located at or
      close to DNA loop anchorage regions.

PMID- 9513044
TI  - Calreticulin associates with stress proteins: implications for chaperone function
      during heat stress.
AB  - Acute heat stress leads to the glycosylation of a "prompt" stress glycoprotein, P
      SG67/64, identified as calreticulin. In the present study, we used
      immunoprecipitation to investigate the interactions of P-SG/calreticulin with
      other proteins during cellular recovery from heat stress. In heat-stressed CHO
      and M21 cells, both glycosylated and unglycosylated P-SGs interact with HSP90,
      GRP94, GRP78, and the other prompt stress glycoprotein, P-SG50, in an ATP
      independent manner. Specificity of HSP-P-SG interactions was determined by
      chemical cross-linking with the homo-bifunctional agent DSP (3,3'
      dithiobis[succinimidyl propionate]). Characterization of the cross-linked
      complexes involving calreticulin and heat shock proteins (HSPs) showed an average
      mass of 400-600 kDa by gel filtration chromatography. Overall, the consistent
      association of glycosylated and unglycosylated calreticulin with P-SG50 and
      unglycosylated HSPs suggests that P-SG/calreticulin is an active member of the
      cast of glycone/aglycone chaperones that cooperate to achieve cellular recovery
      from acute heat stress.

PMID- 9513045
TI  - Genistein inhibits proliferation similarly in estrogen receptor-positive and
      negative human breast carcinoma cell lines characterized by P21WAF1/CIP1
      induction, G2/M arrest, and apoptosis.
AB  - Genistein has been proposed to be responsible for lowering the rate of breast
      cancer in Asian women but the mechanism for this chemopreventive effect in vivo
      is unknown. In this study, we present in vitro evidence that genistein inhibits
      cell proliferation similarly in ER-positive and ER-negative human breast
      carcinoma cell lines. This inhibition is associated with specific G2/M arrest and
      induction of p21WAF1/CIP1 expression. Genistein results in a five-to six-fold
      increase in p21WAF1/CIP1 mRNA levels and a three- to four-fold increase in
      protein levels, only a 1.5-fold increase in p21WAF1/CIP1 transcription but a
      three- to six-fold increase in p21WAF1/CIP1 mRNA stability. The increase in
      p21WAF1/CIP1 is followed by increased apoptosis. The similar effects of genistein
      on a number of breast carcinoma cell lines with different ER and p53 status
      suggest that the actions of genistein reported here are mediated through ER and
      p53 independent mechanisms. The chemopreventive effects of genistein in vivo
      could be mediated along an identical or similar anti-proliferative pathway.

PMID- 9513046
TI  - Downmodulation of TGF-alpha protein expression with antisense oligonucleotides
      inhibits proliferation of head and neck squamous carcinoma but not normal mucosal
      epithelial cells.
AB  - Interruption of an autocrine growth pathway involving TGF-alpha and EGFR may
      inhibit tumor growth and improve survival in head and neck cancer patients. We
      previously demonstrated that biopsy specimens and established cell lines from
      patients with squamous cell carcinoma of the head and neck (SCCHN) overexpress
      TGF-alpha and its receptor, epidermal growth factor receptor (EGFR) at both the
      mRNA and protein levels. Protein localization studies showed that TGF-alpha and
      EGFR are produced by the same epithelial cells in tissues from head and neck
      cancer patients further supporting a role for this ligand-receptor pair in an
      autocrine growth pathway. To confirm that TGF-alpha contributes to autocrine
      growth, we examined the effect of down regulation of TGF-alpha protein on SCCHN
      cell proliferation. Treatment of 6 SCCHN cell lines with antisense
      oligodeoxynucleotides targeting the translation start site of human TGF-alpha
      mRNA decreased TGF-alpha protein production by up to 93% and reduced cell
      proliferation by a mean of 76.2% compared to a 9.7% reduction with sense
      oligonucleotide (range P = 0.036-0.0001). TGF-alpha antisense oligonucleotide
      exposure also decreased TGF-alpha protein levels in normal oropharyngeal mucosal
      epithelial cells, however their growth rate was not affected. These findings
      indicate that TGF-alpha is participating in an autocrine signaling pathway in
      transformed, but not in normal mucosal epithelial cells, that promotes
      proliferation.

PMID- 9513047
TI  - Angiotensin II induces diverse signal transduction pathways via both Gq and Gi
      proteins in liver epithelial cells.
AB  - Angiotensin II stimulates a biphasic activation of Raf-1, MEK, and ERK in WB
      liver epithelial cells. The first peak of activity is rapid and transient and is
      followed by a sustained phase. Angiotensin II also causes a rapid activation of
      p21ras in these cells. Moreover, two Src family kinases (Fyn and Yes) were
      activated by angiotensin II in a time- and concentration-dependent manner.
      Microinjection of antibodies against Fyn and Yes blocked angiotensin II-induced
      DNA synthesis and c-Fos expression in WB cells, indicating an obligatory
      involvement of these tyrosine kinases in the activation of the ERK cascade by
      angiotensin II. Finally, substantial reduction of the angiotensin II-stimulated
      activation of Fyn, Raf-1, ERK, and expression of c-Fos by pertussis toxin
      pretreatment argues that G proteins of the Gi family as well as the Gq family are
      involved in angiotensin II-mediated mitogenic pathways in WB cells.

PMID- 9513049
TI  - Parathyroid hormone effect on cell-to-cell communication in stromal and
      osteoblastic cells.
AB  - We characterized the formation and regulation of the gap junction in calvarial
      osteoblasts and in a series of subtypes from marrow stromal cells. The stromal
      cells included osteogenic, chondro-osteogenic, and endothelial cells. The cell
      coupling was measured by using fluorescence dye injected into single cells, and
      its migration to neighboring cells was measured. The functional coupling of cells
      was highly expressed by the osteoblastic cells. This process is mediated through
      fast changes in intracellular Ca+2 levels. Calcium ionophore (A 23,187)
      demonstrated an uncoupling effect on the cells. In addition, the exposure of the
      cells to the parathyroid hormone increased the formation of the gap junction
      complex; the highest level was demonstrated in the osteoblastic cells.

PMID- 9513048
TI  - Dynamics of distribution of splicing components relative to the transcriptional
      state of human oocytes from antral follicles.
AB  - The distribution of two splicing components (snRNP and SC-35) and coilin were
      studied by immunogold/electron microscopy in human oocytes from antral follicles
      at different levels of transcriptional activity (i.e., active, intermediate, and
      inactive). The results showed a decrease of snRNPs and SC-35 in the karyoplasm as
      the oocytes progress from a transcriptionally active to the inactive state. The
      main areas of accumulation of both these splicing components in all stages of
      oocytes appeared to be the interchromatin granule clusters (IGCs). Within the
      IGCs, the two splicing components seemed to be spatially segregated, with the
      snRNPs predominantly bound to the fibrillar region, whereas the SC-35 factors are
      being enriched in the granular zone. The p80 coilin was found only in the
      nucleolus-like body (NLB), which is present in all three stages of oocytes; no
      coiled bodies were evident. These data are consistent with the notion that
      splicing occurs in the karyoplasm and that the splicing components are mobilized
      from a storage site (IGCs) to the site of action.

PMID- 9513050
TI  - Activation of c-Jun NH2-terminal kinases by interleukin-1 beta in normal human
      osteoblastic and rat UMR-106 cells.
AB  - We recently demonstrated the activation of extracellular signal- regulated
      protein kinase 1 and 2 (ERK1 and ERK2) by IGF-1, FGF-2, and PDGF-BB in normal
      human osteoblastic (HOB) cells as well as in rat and mouse osteoblastic cells. In
      this report, we have examined whether c-Jun NH2-Terminal Kinase (JNK) pathway is
      activated by growth factors and interleukin-1 beta (IL-1 beta) in normal HOB and
      rat UMR-106 cells using immune-complex kinase assay and anti-active JNK antibody,
      which recognizes activated forms of both JNK1 and JNK2. Results have demonstrated
      the presence of JNK1 and JNK2 proteins in normal HOB and UMR-106 cells. Both JNK1
      and JNK2 were activated by IL-1 beta. IL-1 beta preferentially activated JNK
      pathway in a dose- and time-dependent manner and had little effect on ERK
      pathway. On the other hand, FGF-2 did not activate JNK but most strongly
      activated ERK pathway. The activation of JNK was maximal at 20 min whereas
      maximal activation of ERK1 and ERK2 was observed within 10 min. Results have
      clearly demonstrated that IL-1 beta preferentially activates JNK pathway whereas
      FGF-2 activates ERK pathway in normal human and rat UMR-106 osteoblastic cells.

PMID- 9513051
TI  - Partitioning of milk accumulation between cisternal and alveolar compartments of
      the bovine udder: relationship to production loss during once daily milking.
AB  - Experiments were undertaken to validate a method (using adrenaline injection) for
      determination of the size of cisternal and alveolar compartments in the udder, to
      use this method to determine the pattern of milk accumulation in the udder over
      time and to determine the relationship between the size of the alveolar and
      cisternal compartments and tolerance of once daily milking. Cows received
      intrajugular injections of adrenaline (3 mg) immediately before milking, to block
      milk ejection and allow harvesting of the cisternal milk fraction. This was
      followed by removal of the alveolar fraction 30 min later after intrajugular
      oxytocin (5 i.u.) injection. Results obtained were similar to those obtained by
      catheter drainage. The alveolar compartment was 90% full at 16 h post milking
      while the cisternal compartment filled more slowly and was only 70% full at 24 h
      post milking. At full capacity (measured at 40 h), the volumes of milk contained
      in the cisternal and alveolar compartments were similar. In a further experiment
      involving identical twin cows, it was shown that the greater the degree of
      filling of the cisternal compartment at 24 h, the lower was the production loss
      on once daily milking. This suggests that the freedom of the alveoli to drain was
      an important factor in the production loss on once daily milking. Although there
      were significant correlations within twin sets for milk yield and the size of
      udder compartments, the relationship within twin sets for yield loss on once
      daily milking was not statistically significant.

PMID- 9513052
TI  - Effect of forage conservation (hay or silage) and cow breed on the coagulation
      properties of milks and on the characteristics of ripened cheeses.
AB  - Forty-two multiparous dairy cows of three different breeds (Holstein,
      Montbeliarde and Tarentaise) were fed on the same type of forage (natural
      grassland) preserved in the form of either hay (H) or silage (GS), according to a
      changeover design (two 4 week periods). The proportion of concentrate in the diet
      and the energy and nitrogen contents were similar in both treatments. The milk
      produced by these cows was used for the manufacture of Saint-Nectaire type
      cheeses, under controlled and identical cheesemaking technological conditions.
      More cheese was produced with the H treatment milk. The cheeses made with the GS
      treatment milk were more yellow and tended to be more bitter. The other chemical
      and sensory characteristics did not differ much between the two treatments. Of
      the 51 volatile compounds identified, four were in significantly higher
      proportion in the GS than in the H cheeses. Cheeses produced from Tarentaise
      cows' milk were more yellow and their pH was higher than those made with the milk
      of Holstein or Montbeliarde cows. The cheeses from Montbeliarde and Tarentaise
      cows' milk were firmer, more melting and tastier than those made with the milk of
      Holstein cows. Although some trends were apparent, there were no significant
      differences in cheese volatile compounds for different breeds.

PMID- 9513053
TI  - Effect of altering the daily herbage allowance to cows in mid lactation on the
      composition, ripening and functionality of low-moisture, part-skim Mozzarella
      cheese.
AB  - Milk was collected from three spring-calving herds, on different daily herbage
      allowances (DHA) of perennial rye-grass (16, 20 or 24 kg dry matter (DM)/cow for
      a 17 week period. On five occasions, at weekly intervals in the middle of the
      period, the three different milks were converted into low-moisture part-skim
      Mozzarella cheese. Increasing the DHA resulted in significant increases in the
      concentrations of protein in the cheesemilk (P < 0.05) and cheese whey (P <
      0.02). The moisture-adjusted cheese yield increased significantly (P < 0.01) on
      raising the DHA from 16 to 24 kg grass DM/cow. DHA had no significant effects on
      any of the gross compositional values of the cheese (although moisture and fat-in
      DM levels tended to decrease and increase respectively with increasing DHA). The
      hardness of the uncooked cheese and functionality of cooked cheese (i.e. melt
      time, flowability, stretch and viscosity) were not significantly influenced by
      DHA over the 115 d ripening period at 4 degrees C.

PMID- 9513054
TI  - Subclinical mastitis assessed by deviations in milk yield and electrical
      resistance.
AB  - Concurrent falls in milk production and electrical resistance of composite milk
      were examined in Israeli Holstein cows. The cows were milked three times a day by
      a system that recorded yield and the lowest electrical resistance in the
      composite milk from the four glands. The study included two groups: cows that
      experienced on day 0 a decline in resistance and milk production > or = 20% from
      the mean of the previous 9 d (62 cows, case group) and cows that experienced no
      such episodes over 9 d before and after a fixed day (118 cows, control group).
      Bacteriological status and somatic cell count (SCC) or California mastitis test
      scores were assessed on the fixed day in the control group, and on days 0, 1 and
      2 in the case group. California mastitis test scores greater than 2 and SCC
      thresholds of 5 x 10(5) cells/ml were used to create two classes of leucocytosis.
      There was no statistically significant difference between the two groups in
      frequency distributions of pathogens and their types: in 30% of cows infection
      was not detected, 33% were infected by major pathogens (95% of which were
      Staphylococcus aureus), and 53.5% by minor pathogens (80% Micrococcus spp.). Cows
      in the case group had lower milk production during the 8 d following day 0. Mean
      electrical resistance was lower in infected cows and particularly in cows
      infected by Staph. aureus. High leucocytosis was associated with reduced
      electrical resistance in both groups, and was found in 93% of cows in the case
      group v. 25% in the control group. The results suggest that falls in electrical
      resistance of milk and in milk production were not linked to a specific pathogen,
      and were followed by 3-8 d of reduced milk production and electrical resistance.
      The study suggests that there are episodic aggravations in mammary health that do
      not evolve into clinical mastitis but may induce significant losses in milk yield
      and quality.

PMID- 9513055
TI  - Localization of carbonic anhydrase in the goat mammary gland during involution
      and lactogenesis.
AB  - The aim of this study was to determine whether carbonic anhydrase (CA) activity
      in goat mammary capillaries is regulated mainly by local or systemic mechanisms.
      One gland was dried before the contralateral gland, and after parturition only
      one gland was milked. Biopsies were taken from the mammary glands of three goats
      at 14 d intervals during involution and the start of the following lactation. A
      histochemical method was used to visualize sites of CA activity. To follow the
      involution process, milk (liquid) samples were taken from both teats each week
      and analysed for pH and composition. The time course of CA activity disappearance
      and reappearance in the capillaries was related to changes in milk composition
      and alveolar area. A dense network of capillaries showing membrane-bound staining
      for CA was found surrounding the alveoli in the lactating gland. CA activity
      gradually decreased in the drying gland, although the other gland was being
      milked. After 8 weeks involution the dried gland had a significantly lower number
      of stained capillaries than the milked gland. Almost no stained capillaries were
      found during late pregnancy, when both glands were dried and the tissue growth
      maximal. During lactation milk pH was 6.6 +/- 0.3 and this increased to 7.0 +/-
      0.1 in the course of involution. In the last trimester of pregnancy the pH
      returned to its lower value, while the mammary gland was devoid of stained
      capillaries. Therefore, the capillary CA could not have been directly involved in
      the pH regulation of milk. The CA activity reappeared in the capillaries directly
      after delivery, but only in the milked gland. Clearly the regulation of CA
      activity is influenced more by local than by systemic factors and is associated
      with the metabolic activity of milk secretion.

PMID- 9513056
TI  - Citrate, calcium, phosphate and magnesium in sows' milk at initiation of
      lactation.
AB  - Colostrum and milk were collected from ten sows at frequent intervals from before
      farrowing until 9 d after farrowing. Ionized calcium, pH, and total
      concentrations of citrate, calcium, phosphate and magnesium were measured in
      whole milk. The diffusible fraction of the mammary secretion was separated by
      ultrafiltration and was used for the measurement of diffusible citrate, calcium,
      phosphate and magnesium. The pH before farrowing was 5.7, and increased to 6.5 on
      day 4 as total calcium and phosphate also increased. Before farrowing, total and
      diffusible citrate were 7.8 and 7.3 mM respectively, while diffusible phosphate
      was 11.9 mM, and these concentrations all decreased during the study period.
      Total magnesium ranged between 3.3 and 4.1 mM, while diffusible magnesium ranged
      between 2.0 and 3.1 mM. While these concentrations and patterns of change of
      diffusible calcium and citrate are quite different from those of women's milk
      during the first week after birth, theoretical physicochemical relationships
      between diffusible calcium and citrate, and ionized calcium and HPO4(2-) were
      corroborated by these results. We conclude that diffusible citrate plays an
      important role in the determination of the concentration of diffusible calcium.
      However, while citrate may be the major determinant of the total concentration of
      calcium in women's milk, this is not the case in sows' milk.

PMID- 9513057
TI  - Growth factors in milk: interrelationships with somatic cell count.
AB  - Growth factors are thought to play a decisive role in the course of inflammatory
      processes. The aim of the present study was to characterize a potential
      interrelationship between the concentrations of insulin-like growth factor-1 (IGF
      1), basic fibroblast growth factor (bFGF) and somatic cell count (SCC) in normal
      milk, and to investigate the presence of these growth factors in mammary
      secretions of cows suffering from clinical and subclinical mastitis. Quarter
      secretions of cows with spontaneous acute clinical mastitis and of cows with
      subclinical mastitis were analysed radioimmunologically for their concentrations
      of IGF-1 and bFGF. During two relocation trials with normally lactating Brown
      Swiss cows, dramatic changes in milk somatic cell count were obtained following a
      short-term change (5 d) of location and housing system. The animals were
      relocated from their familiar loose housing system with concrete slatted floor to
      a separate stanchion barn with long stalls and straw bedding, and vice versa. The
      concentration profile of IGF-1, but not of bFGF, corresponded well with SCC
      during the relocation trials, the positive correlation between the
      characteristics being highly significant, as determined by regression analysis (r
      = 0.60; P < 0.001). The results provide evidence that significant changes in SCC
      and growth factor content may be caused by environmental factors other than
      infection. The concentrations of both IGF-1 and bFGF were greatly elevated in
      secretions of quarters affected by acute clinical mastitis compared with the
      corresponding clinically healthy quarters. Subclinically affected quarters with
      high SCC, as compared with non-affected quarters with low SCC, also had elevated
      milk IGF-1, but unchanged bFGF. Measuring of growth factor profiles in milk may
      have value in the near future in monitoring the state of udder health in addition
      to SCC.

PMID- 9513058
TI  - Changes in the concentrations of free amino acids in milk during growth of
      Lactococcus lactis indicate biphasic nitrogen metabolism.
AB  - Analysis of the concentrations of free amino acids in milk during growth of
      Lactococcus lactis subsp, lactis revealed a biphasic pattern of change during the
      logarithmic phase. During the first period there was little overall change in the
      total concentration of amino acids in the medium. The second phase was
      characterized by increased net liberation of free amino acids. There were also
      qualitative differences in the amino acids that were taken up and utilized during
      each period. The concentrations of Val, Leu and Ile decreased only during the
      early phase, while those of Ser, Arg, Thr and Met decreased only during the
      second phase. Gly and Ala were utilized throughout logarithmic growth. Gly uptake
      appeared to be greater during the second period and accounted for the largest
      proportion of free amino acid utilization at this time. It is possible that the
      biphasic nature of amino acid nutrition was due to increased consumption in late
      log phase of peptides derived from milk proteins by proteolysis. Increased
      activity of the arginine deiminase pathway during late log phase was inferred
      from increased utilization of Arg and liberation of citrulline and ornithine.

PMID- 9513060
TI  - Isolation of coagulase-negative staphylococci from the milk and environment of
      sheep.
AB  - Various species of coagulase-negative staphylococci (C-NS) are reported to be
      common in milk and on the teat skin of domestic ruminants. The commonest C-NS
      species in mastitic milk of cows varies between reports, with Staphylococcus
      simulans (Jarp, 1991) in one and Staph. hyicus in another (Watts & Washburn,
      1991). The teat skin of heifers may be colonized by Staph. xylosus or Staph.
      chromogenes, while Staph. chromogenes and Staph. warneri are reported as frequent
      isolates from teat canals and secretion (Boddie & Nickerson, 1986; White et al.
      1989). Staph. haemolyticus was isolated frequently from the nares, the teat skin
      and the milk of goats (Valle et al. 1991), although others reported Staph.
      xylosus (Bedidi-Madani et al. 1992) or Staph. epidermidis and Staph. capitis
      (Kalogridou-Vassiliadou, 1991) as the most predominant C-NS in goats' milk.
      Staph. simulans has been found experimentally to be pathogenic for the mammary
      gland of meat ewes (Fthenakis & Jones, 1990), but little is known about the
      prevalence of this species in ewes' milk collected from cases of naturally
      occurring subclinical mastitis (SCM). The aim of the present investigation was
      the identification of the commonest C-NS species in ewes' milk collected from
      field cases of SCM or predominating in the ewes' environment.

PMID- 9513059
TI  - Antitumour activity of yogurt: study of possible immune mechanisms.
AB  - The effect of yogurt on the inhibition of colon tumours induced by 1,2
      dimethylhydrazine in BALB/c mice has been studied, and the hypothesis examined
      that yogurt induces a great reduction in the inflammatory immune response and
      inhibits tumour growth. Mice were assigned to five experimental groups: a control
      group fed with a conventional balanced diet, and four other test groups that
      received yogurt supplements for 2, 5, 7 or 10 consecutive days. At the end of
      each feeding period, mice were given subcutaneous injections of 1,2
      dimethylhydrazine (20 mg/kg) once a week for 8 weeks. After tumour induction,
      yogurt was given again for 2, 5, 7 or 10 consecutive days each 10 d for 20 weeks.
      By week 20, 70% of the animals in the control group had developed colorectal
      tumours. From week 8, there was a considerable infiltration of mononuclear cells
      into the lamina propria of the large intestine. There was an increase in the
      number of IgG-producing cells and a slight increase in the IgA-secreting cells,
      and of CD8+ but not CD4+ T lymphocytes, a high level of beta-glucuronidase
      activity in the intestinal fluid and leucocytosis with neutrophilia in the blood.
      However, in the test groups given yogurt tumour growth was inhibited, the effect
      being more evident with 7 or 10 d treatment. The inflammatory immune response as
      measured by the characteristics we assessed was also reduced, with an increase in
      the IgA-secreting cells and in CD4+ T lymphocytes. The blood count was similar to
      that of normal animals and no colorectal tumours were observed in week 20. We
      suggest that one of the mechanisms by which yogurt exerts antitumour activity is
      through its immunomodulator activity, by reducing the inflammatory immune
      response, which was markedly increased when the carcinogen was administered.

PMID- 9513061
TI  - Detection of enterocin AS-48-producing dairy enterococci by dot-blot and colony
      hybridization.

PMID- 9513062
TI  - Body score of dairy cows.
AB  - Body CS measurement, based on a standardized technique leading to a numerical
      assessment, provides a cheap, easily applied measure of fatness in cattle and
      hence an immediate absolute appraisal that avoids the problems of live weight.
      The scale is limited and the divisions are coarse. The nutritional significance
      of CS/C has received considerable research attention. Higher CS/C is associated
      with smaller feed intake in early lactation, increased loss of CS, increased fat
      content of milk, especially when the general content is low, and slightly reduced
      milk protein content. Evidence on the effect of CS/C on subsequent MY is
      conflicting: some experiments have shown a benefit from increased CS/C but others
      have not. This outcome may depend on the plane of nutrition after calving. CS/C
      values > 3.25 have led to small decreases in MY. During lactation, CS responds to
      change in plane of nutrition in parallel with MY, milk protein content, and live
      weight. Some but not all the available evidence indicates that the fall in CS in
      early lactation may be limited physiologically, and subsequent recovery of body
      reserves may be characterized by a compensatory partition of nutrients to body as
      well as a response to increased plane of nutrition relative to requirements for
      milk production. Further investigation is required regarding application of CS to
      mid to late lactation, particularly partition of nutrients between milk and body,
      to multiple lactations, to health and fertility, and to CS in relation to the cow
      potential.

PMID- 9513063
TI  - Monitoring infective complications following hip fracture.
AB  - Hip fracture affects more than 55,000 people in the UK each year and this number
      is increasing. Because of their advanced age and other risk factors, hip fracture
      patients are at risk of developing infection and a variety of other non-infective
      complications. Surveillance of superficial wound and deep joint infection is
      important because of the large number of patients involved and represents a good
      example of targeted surveillance. Furthermore this may be conducted as part of a
      quality control programme monitoring other interventions such as prophylaxis for
      vascular thrombosis. However, to carry this out successfully, a simple but
      efficient system for recording, collecting and analysing data is required and
      adequate post-discharge surveillance must be carried out.

PMID- 9513065
TI  - Molecular epidemiology of Burkholderia cepacia in two Australian cystic fibrosis
      centres.
AB  - Forty individual patient sputum isolates of Burkholderia cepacia from two
      Australian cystic fibrosis (CF) centres more than 100 km apart were genotyped
      using pulsed-field gel electrophoresis (PFGE) with XbaI restriction enzyme
      digestion. Hospital 1 had an endemic strain with 19 of 20 isolates being closely
      related. This centre does not implement an inpatient segregation policy for its
      paediatric patients who constitute the majority of those colonized with B.
      cepacia. Hospital 2 did not have a single endemic strain; there were two
      different sibling clusters and a third cluster involving a cohabiting couple, but
      all other patients had unique isolates. One patient at Hospital 2 carried an
      organism closely related to the endemic strain from Hospital 1. Hospital 2
      practises segregation of colonized inpatients and also segregation external to
      the hospital. It would appear that no nosocomial spread of infection is occurring
      with this policy.

PMID- 9513064
TI  - Invasive aspergillosis in severely neutropenic patients over 18 years: impact of
      intranasal amphotericin B and HEPA filtration.
AB  - The impact of intranasal amphotericin B and high-efficiency particulate air
      (HEPA) filtration on the incidence of invasive aspergillosis was reviewed in
      patients from 1977 to 1994 undergoing intensive chemotherapy. Overall, the
      incidence of proven invasive aspergillosis was reduced from 24.4% (1977-1984) to
      7.1% (1985-1991) (P < 0.001) following the introduction of intranasal
      prophylaxis, but when probable cases of aspergillosis were included and lymphoma
      cases excluded, there was no change in incidence. Following the introduction of
      HEPA filtration, patient exposure to aspergillus spores as measured by air
      sampling was markedly reduced and there were no new cases of invasive
      aspergillosis. HEPA filtration proved effective in reducing invasive
      aspergillosis and has allowed increasingly aggressive treatment regimens to be
      introduced.

PMID- 9513066
TI  - Evaluation of clinical and laboratory findings in leukaemic patients with blood
      cultures positive for Staphylococcus epidermidis.
AB  - It is not certain whether clinical or laboratory findings help to distinguish
      true bacteraemia from contamination among acute leukaemic patients with one or
      more blood cultures positive for Staphylococcus epidermidis. We studied 31
      patients treated at the Haematological Unit between 1 January, 1992 and 30 June,
      1995 who were considered to have 'true bacteraemia', indicated by at least two
      positive blood cultures, and 20 considered to have probable 'contamination',
      indicated by a single positive culture. Fever at onset of positive blood culture,
      level of C-reactive protein (CRP) one day after the first positive blood culture
      and mortality did not differ between the groups. However, the median increase in
      CRP over 24 h from the first positive blood culture was significantly higher in
      true bacteraemias than among contaminants (median 35 mg/L vs 5 mg/L, P < 0.05).
      Patients with true bacteraemia were more likely than those with contaminants to
      have central catheters in situ (95 vs 75%, P < 0.05) and previous oral antibiotic
      prophylaxis (29 vs 5%, P < 0.05). Also clinical signs of catheter infection (30
      vs 7%) were more common in true bacteraemias. In conclusion, central
      catheterization, antibiotic prophylaxis and clinical signs of catheter infection
      increase the likelihood of true bacteraemia; however, these factors have limited
      clinical utility in differentiation of true bacteraemia from contamination. Daily
      monitoring of serum CRP levels may help in the clinical decision-making.

PMID- 9513067
TI  - Prevalence of nosocomial infections in representative German hospitals.
AB  - The nosocomial infection (NI) rate in German hospitals was studied in order to
      create reference data for comparison in hospitals where ongoing surveillance is
      impossible. The study was designed as a one-day prevalence study. Patients in 72
      selected hospitals (inclusion criteria: acute care hospitals with departments for
      general medicine, surgery, obstetrics/gynaecology) were examined by four external
      investigators (physicians trained and validated in the diagnosis of NI). A total
      of 14,996 patients were studied. The overall prevalence rate was 3.5% (CI 3.1
      3.9) with a variation of 0-8.9% between hospitals. The commonest NI were: urinary
      tract infection (42.1%), lower respiratory tract infection (20.6%), surgical site
      infections (15.8%) and primary sepsis (8.3%). The highest prevalence rate (15.3%)
      was found in intensive care ward patients, followed by surgery (3.8%), general
      medicine (3.0%) and gynaecology/obstetrics (1.4%). The infection rate varied
      significantly with hospital size. A microbiology laboratory report was only
      available for 56.5% of patients thought to have an NI, and there were remarkable
      differences between hospitals with and without an on-site microbiology
      laboratory. Because of this and other methodological reasons the NI prevalence
      rates reported here may represent the absolute minimum of nosocomially infected
      patients in Germany.

PMID- 9513068
TI  - Device-associated nosocomial infection surveillance in neonatal intensive care
      using specified criteria for neonates.
AB  - Agreement on criteria for defining nosocomial infections is essential when
      surveillance is intended for quality assurance. The CDC criteria for patients <
      12 months old were compared with locally developed criteria for neonates in a 10
      month study of nosocomial infections in a Berlin University hospital. Six hundred
      and seventy-seven neonates were observed prospectively for 11,936 patient days.
      The overall nosocomial infection incidence rate was 13.2%. Because of the
      observed strength of agreement between the CDC and local criteria for central
      line-associated primary bloodstream infections and for ventilator-associated
      pneumonias (recommended by the NNIS system for inter-hospital comparisons) and
      the preference of the clinicians for the local criteria, we decided to use the
      latter for an ongoing surveillance system which nonetheless would retain the
      possibility for comparison with NNIS-data.

PMID- 9513069
TI  - Microbial contamination of 'sterile water' used in Japanese hospitals.
AB  - We examined the following samples of water from 10 hospitals for microbial
      contamination: water obtained using an ultra filtration system (UF water), a
      reverse osmosis system (RO water), a water distillation system (distilled water)
      and tap water. UF water and RO water are used for handwashing before surgery, and
      distilled water for the preparation of drugs. All 10 samples of tap water
      examined were contaminated with < 10 colony forming units (cfu)/mL. Thirteen
      (68%) of 19 samples of UF water, nine (53%) of 17 samples of RO water and 15
      (79%) of 19 samples of distilled water were contaminated with 10(1)-10(4) cfu/mL.
      The majority of micro-organisms were non-fermentative bacteria such as
      Sphingomonas paucimobilis and CDC gr. IV C-2. Japanese hospitals commonly use UF
      water and RO water for preoperative handwashing under the assumption that it is
      sterile. Our results suggest, however, that these types of water are inferior
      microbiologically to tap water. Distilled water from the dispensary was also
      contaminated with micro-organisms. The available chlorine content of tap water
      was 0.17-0.42 ppm and that of UF water (from tap water) 0-0.06 ppm. There was no
      available chlorine in RO water or distilled water (each from tap water). The
      reduction or disappearance of available chlorine appears to be associated with
      microbial contamination of UF water, RO water and distilled water.

PMID- 9513070
TI  - Environmental contamination due to methicillin-resistant Staphylococcus aureus
      (MRSA).

PMID- 9513071
TI  - Infecting organisms in primary total joint replacement.

PMID- 9513072
TI  - Steroid formation in osteoblast-like cells.
AB  - For preventing the reduction of bone mass in postmenopausal women, oestrogen
      replacement is known to be useful and the importance of sex steroids in bone
      metabolism in both sexes is well established. The presence of steroid-converting
      enzyme activities in various osteoblast and osteoblast-like cells has been
      demonstrated using in vitro culture systems. In the present study, we assessed
      the expression of messenger ribonucleic acid (mRNA) for aromatase, steroid
      sulphatase, 5 alpha-reductase, 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD)
      and 3 beta-HSD by reverse transcription-polymerase chain reaction in the human
      osteoblast-like cell lines, MG 63 and HOS. Oestrogen, androgen and progesterone
      receptor mRNAs were also measured. Expression of mRNA for these enzymes and
      receptors was found in both cell lines without induction. From these and previous
      findings, we conclude that osteoblast-like cells have the capacity to form
      biologically potent oestrogens and androgens from peripheral circulating
      steroids. This may indicate an important role of bone in facilitating hormonal
      action.

PMID- 9513073
TI  - Comparison of continuous versus intermittent administration of zolpidem in
      chronic insomniacs: a double-blind, randomized pilot study.
AB  - The subjective efficacy and safety of intermittent administration of a hypnotic
      for insomnia was assessed, since such a regime may provide a potential means of
      reducing the risk of habituation and dependence. A total of 160 adult patients
      (mean 45 years) with chronic insomnia were treated for 2 weeks with zolpidem, 10
      mg, either continuously or intermittently (five nights zolpidem, two consecutive
      nights placebo per week) in this multicentre, out-patient, pilot study. At the
      end of the 2-week treatment, patients subjectively estimated their nightly total
      sleep time as 6.96 +/- 1.19 h (from 6.07 +/- 1.25 h at baseline) and 6.94 +/-
      1.30 h (from 5.72 +/- 1.46 h) after the continuous and intermittent treatments,
      respectively. Patients' reports did not indicate any differences between the two
      groups in global evaluation of impairment, sleep quality, or the incidence of
      adverse events. These results suggest that the efficacy and safety of zolpidem,
      10 mg, are comparable whether the drug is administered every night or
      intermittently. Further studies with a broader well-defined patient base, are
      needed to confirm these data.

PMID- 9513074
TI  - Effects of changing the type of H2-blocker in the treatment of H2-blocker
      resistant ulcers: comparison of roxatidine acetate hydrochloride and other H2
      blockers.
AB  - The efficacy of switching from one type of H2-receptor antagonist (H2-blocker) to
      another, in the treatment of H2-blocker-resistant ulcers was investigated using
      H2-blockers with five-membered rings (five-membered-ring agents)--such as
      cimetidine, ranitidine and famotidine--and an H2-blocker with a six-membered
      ring, roxatidine. By switching from a five-membered-ring agent to roxatidine in
      the treatment of five-membered-ring resistant ulcers (study I), gastric ulcers
      were healed in nine of 19 patients (47%) and duodenal ulcers were healed in eight
      of nine patients (89%). By switching from roxatidine to one of the five-membered
      ring agents in the treatment of roxatidine-resistant ulcers (study II), gastric
      ulcer was healed in six of 15 patients (40%), and duodenal ulcer was healed in 4
      of 10 patients (40%). Particularly in the case of duodenal ulcers, the switch to
      treatment with roxatidine, which has a different chemical structure from the five
      membered-ring agents, may be useful in the treatment of five-membered-ring
      resistant ulcers.

PMID- 9513075
TI  - Expression of beta 1 integrins (very late antigens-4 and -5) on myeloma cells and
      clinical correlates in patients with multiple myeloma.
AB  - beta 1 Integrins are considered to be essential for the differentiation of bone
      marrow B cells through an interaction with fibronectin-expressed bone-marrow
      stromal cells. The expression of very late antigens-4 (VLA-4) and -5 (VLA-5) by
      CD38bright bone-marrow cells in patients with multiple myeloma was measured by
      flow cytometry using specific monoclonal antibodies. The percentage of CD38bright
      bone-marrow cells appeared to correlated with that of bone-marrow plasma cells as
      judged by examination of bone-marrow smears (r = 0.911, P < 0.0001). Expression
      of VLA-4 and VLA-5 by CD38bright cells varied between patients, but the
      expression of VLA-4 was always equal to or greater than that of VLA-5. The ratio
      of VLA-4 to VLA-5 expression (VLA-4:VLA-5 ratio) was calculated and compared with
      the clinical features of the myeloma patients. A high VLA-4:VLA-5 ratio (> 2.0)
      was associated with the presence of plasmacytomas and urinary Bence-Jones protein
      was more common in this group. No other correlations between the clinical
      features of the disease and the expression of beta 1 integrins were found.

PMID- 9513077
TI  - New technique for mediastinal temperature measurement in hyperthermic cancer
      treatment: balloon catheter in the azygos vein.
AB  - The temperature in the mediastinum during hyperthermia is difficult to determine
      accurately. We measured the temperature in the azygos vein, using a new
      technique, and compared the measurements with temperatures in the oesophagus.
      Eight patients with mediastinal tumours resulting from lung cancer or oesophageal
      cancer were given hyperthermo-radiotherapy. The temperatures in the azygos vein
      and in the oesophagus were measured before and during blockage of the blood flow
      of the azygos vein using an angiographic balloon catheter. None of the patients
      had complications as a result of these procedures, and hyperthermia by
      capacitative heating was safely performed. The temperature in the azygos vein
      increased by a mean of 1.7 degrees C (0.2-2.8 degrees C) after blockage of the
      blood flow. The temperature in the oesophagus was 0.83 +/- 1.09 degrees C (mean
      +/- SD) higher than that in the azygos vein. Measurement of the temperature in
      the azygos vein gives a more accurate estimate of mediastinal temperature than
      does oesophageal temperature but it is an invasive procedure.

PMID- 9513076
TI  - Immune profiles in hepatosplenic schistosomiasis mansoni after surgical
      treatments.
AB  - The hepatosplenic form of schistosomiasis mansoni sometimes induces bleeding in
      oesophageal varices that requires surgical treatment. Although splenectomy is
      often necessary these patients rarely present with septic events, a finding that
      may be related to changes in the immunological system. To investigate the
      immunological profiles of patients with schistosomiasis, we studied the B- and T
      lymphocyte counts and the immunoglobulin A, G and M (IgA, IgG and IgM) levels in
      patients treated surgically and in those who were not operated on. Patients who
      underwent distal splenorenal shunt, preserving the spleen, showed significantly
      increased T-lymphocyte counts compared with healthy controls. The IgM and IgG
      levels were significantly increased compared with the healthy controls in
      patients submitted to partial and total splenectomy, respectively. The IgM level
      also tended to increase in patients who were not operated on compared with the
      controls. These results suggest that chronic schistosomiasis may influence the
      immune system.

PMID- 9513078
TI  - Origin, proliferation and differentiation of Leydig cells.

PMID- 9513080
TI  - Differential expression of milk protein genes during lactation in the common
      brushtail possum (Trichosurus vulpecula).
AB  - In the common brushtail possum (Trichosurus vulpecula) lactation lasts for 200
      days and consists of two distinct phases. Milk composition changes dramatically
      between phase 2 and 3, which correspond to early and late lactation respectively
      (phase 1 corresponds to pregnancy). RNA expression patterns have been established
      for eight major milk protein genes throughout lactation in possum mammary glands.
      The levels of mRNA expressed from two genes, encoding the early and late
      lactation proteins, were differentially regulated during lactation, with peak RNA
      levels occurring in phase 2 and 3 of lactation respectively. Expression of these
      two RNA transcripts did not overlap, and neither gene was expressed at
      significant levels between days 116 to 125, suggesting that the transition from
      phase 2 to phase 3 of lactation occurs at this time. The level of lysozyme, alpha
      lactalbumin and trichosurin mRNA increased in phase 3 of lactation, whereas the
      levels of beta-lactoglobulin, alpha-casein and beta-casein mRNA remained constant
      throughout lactation. In the non-suckled gland, expression of milk protein genes
      was greatly reduced by day 6 of lactation. In conclusion, the early and late
      lactation protein genes are good markers for phase 2 and 3 of lactation, with the
      transition between these phases occurring around day 120 of lactation in the
      possum.

PMID- 9513079
TI  - Molecular characterisation and hormone-dependent expression of the porcine whey
      acidic protein gene.
AB  - A 17.5 kDa protein was isolated from porcine whey by reverse phase HPLC and
      identified as a putative whey acidic protein (WAP) homologue by sequencing 35 and
      40 amino acid residues of the amino- and carboxy-terminus respectively.
      Degenerate oligonucleotides to both of these amino acid sequences were designed
      and used in reverse transcriptase PCR with RNA from lactating porcine mammary
      gland as a template. A 162 bp PCR fragment was detected and sequenced.
      Compilation of the deduced and determined amino acid sequence revealed a protein
      of 111 amino acids, which had approximately 75, 50, 40 and 35% similarity at
      amino acid level to camel, rabbit, rat and mouse WAP respectively. It also
      included the four-disulphide core characteristic of all WAP proteins and most
      Kunitz-type protease inhibitors. This provides the first unequivocal evidence for
      WAP secretion in the pig. SDS PAGE analysis of the whey fraction showed that WAP
      is secreted as a major protein in sow's milk from farrowing to weaning. The
      molecular mass of WAP in SDS PAGE was significantly greater than the 11.7 kDa
      determined from amino acid sequence, indicating that porcine WAP is possibly
      glycosylated. Northern analysis detected a single mRNA transcript of
      approximately 600 bp in porcine RNA from the mammary gland of lactating sows. To
      examine the hormone-regulated expression of the WAP gene the mammary glands of
      sows at day 90 of pregnancy were biopsied and explants cultured for 3 days in the
      presence of various combinations of porcine insulin (I), cortisol (F) and porcine
      prolactin (P). Northern analysis of RNA extracted from the tissue indicated that
      WAP gene expression was barely detectable in the mammary gland prior to culture
      and there was no increment in explants cultured in the presence of I and F.
      However, a significant increase in the accumulation of WAP mRNA was observed in
      explants cultured in I, F and P. A similar result was observed for beta-casein
      and alpha-lactalbumin gene expression.

PMID- 9513081
TI  - Effect of the triakontatetraneuropeptide (TTN) on corticosteroid secretion by the
      frog adrenal gland.
AB  - Diazepam-binding inhibitor (DBI) was initially isolated from the rat brain as a
      result of its ability to compete with benzodiazepines for their receptors.
      Immunohistochemical studies have recently shown the presence of peripheral-type
      benzodiazepine receptor (PBR)- and DBI-like immunoreactivity in the frog adrenal
      gland. The aim of the present study was to investigate the effect of two
      biologically active DBI-derived peptides, the triakontatetraneuropeptide [TTN;
      DBI(17-50)] and the octadecaneuropeptide [ODN; DBI(33-50)], on corticosteroid
      secretion by frog adrenocortical cells. Exposure of frog adrenal explants to
      graded concentrations of TTN (3.16 x 10(-8) to 3.16 x 10(-6) M) induced a dose
      related increase in corticosterone and aldosterone secretion. In contrast, ODN
      did not modify corticosteroid output. When repeated pulses of TTN (10(-6) M) were
      administered at 2-h intervals, the response of the adrenal explants to the second
      dose of TTN was markedly reduced, suggesting the existence of a desensitization
      phenomenon. Exposure of dispersed adrenal cells to TTN also induced a marked
      stimulation of corticosteroid secretion, indicating that TTN acts directly on
      adrenocortical cells. The central-type benzodiazepine receptor (CBR) agonist,
      clonazepam, did not stimulate corticosteroid secretion and the CBR antagonist,
      flumazenil, did not block the stimulatory action of TTN. Similarly, the PBR
      agonist, Ro5-4864, did not mimic the stimulatory effect of TTN and the PBR
      antagonist, flunitrazepam, did not affect the stimulatory action of TTN. The
      present study provides the first evidence for a stimulatory effect of TTN on
      intact adrenocortical cells. The receptor mediating the corticotropic action of
      TTN is not related to central- or peripheral-type benzodiazepine receptors. Our
      data suggest that TTN, released by chromaffin cells, may act as a paracrine
      factor regulating the activity of adrenocortical cells.

PMID- 9513082
TI  - Expression and purification of biologically active porcine follicle-stimulating
      hormone in insect cells bearing a baculovirus vector.
AB  - Biologically active recombinant porcine FSH (rec-pFSH) free from the cognate
      pituitary glycoprotein hormone LH was produced. It was synthesized by a
      baculovirus vector-insect cell system using two cDNAs encoding the glycoprotein
      alpha and FSH beta subunits. Its antigenicity was the same as that of pFSH
      prepared from the pituitary. Glycosylation of rec-pFSH was shown by tunicamycin
      treatment but the molecular mass of each subunit was lower than that of pituitary
      derived FSH, because of the absence of trimming of terminal sugars in insect
      cells. Rec-pFSH was secreted into the culture medium at about 1 mg/l and purified
      in six fractions, because of the heterogeneity of the sugar group, by S-Sepharose
      and concanavalin A-Sepharose column chromatography. The biological activity of
      rec-pFSH was examined by measuring its effect on progesterone secretion from
      porcine granulosa cells and germinal vesicle breakdown (GVBD) of porcine oocytes.
      It showed adequate activity with respect to progesterone secretion, although some
      fractions rich in the sugar group showed lower activity than that of pituitary
      derived FSH. It exhibited higher GVBD activity than that of pituitary-derived FSH
      at concentrations as low as 1 ng/ml. These results demonstrate that the
      baculovirus vector-insect cell system can provide biologically active rec-pFSH.

PMID- 9513083
TI  - Mouse 17 beta-hydroxysteroid dehydrogenase type 2 mRNA is predominantly expressed
      in hepatocytes and in surface epithelial cells of the gastrointestinal and
      urinary tracts.
AB  - 17 beta-Hydroxysteroid dehydrogenase (17HSD) type 2 efficiently catalyzes the
      conversion of the high activity 17 beta-hydroxy forms of sex steroids into less
      potent 17-ketosteroids. In the present study in situ hybridization was utilized
      to analyze the cellular localization of 17HSD type 2 expression in adult male and
      female mice. The data indicate that 17HSD type 2 mRNA is expressed in several
      epithelial cell layers, including both absorptive and secretory epithelia as well
      as protective epithelium. In both males and females, strong expression of 17HSD
      type 2 was particularly detected in epithelial cells of the gastrointestinal and
      urinary tracts. The mRNA was expressed in the stratified squamous epithelium of
      the esophagus, and surface epithelial cells of the stomach, small intestine and
      colon. The hepatocytes of the liver and the thick limbs of the loops of Henle in
      the kidneys, as well as the epithelium of the urinary bladder, also showed strong
      expression of 17HSD type 2 mRNA in both male and female mice. In the genital
      tracts, low 17HSD type 2 expression was detected in the seminiferous tubules, the
      uterine epithelial cells and the surface epithelium of the ovary. Expression of
      the mRNA was also detected in the sebaceous glands of the skin. The results
      indicate that in both male and female mice, 17HSD type 2 is expressed mainly in
      the various epithelial cell types of the gastrointestinal and urinary tracts, and
      therefore suggest a role for the enzyme in steroid inactivation in a range of
      tissues and cell types not considered as classical sex steroid target tissues.

PMID- 9513084
TI  - Expression of GLUT2 in insulin-secreting AtT20 pituitary cells.
AB  - The importance of the glucose transporter isoform, GLUT2, in the construction of
      glucose-sensitive surrogate insulin-secreting cells was evaluated using murine
      pituitary AtT20 cells. The cells were double transfected with cDNAs for human
      preproinsulin (hppI-1) driven by the cytomegalovirus promoter, and human GLUT2
      driven by the beta-actin promoter. The stably transfected clone, AtTinsGLUT2.36,
      which strongly expressed both the hppI-1 and GLUT2 genes, constitutively released
      7.5 ng/10(6) cells/24 h of immunoreactive insulin-like material, 75% of which was
      fully processed mature human insulin. Increasing glucose concentrations in the
      subphysiological range up to 50 microM increased insulin release, but greater
      glucose concentrations did not further increase insulin release. Suppression of
      the low-K(m) glucose-phosphorylating enzyme, hexokinase, with 2-deoxy-D-glucose
      increased glucose-stimulated insulin release by two- to threefold in the presence
      of subphysiological and physiological glucose concentrations up to 10 mM.
      Physiological glucose concentrations increased the amount of GLUT2 mRNA,
      indicating that the beta-actin promoter responds in a glucose-dependent manner.
      Implantation of 2 x 10(7) AtTinsGLUT2.36 cells intraperitoneally into
      streptozotocin-diabetic nude mice slowed the progression of hyperglycaemia. The
      implanted cells formed vascularised tumour-like cell aggregates attached to the
      peritoneum. The results demonstrate that the beta-actin promoter is partially
      regulated by glucose. Expression of GLUT2 enables glucose to enter the cell at
      high K(m), but high-K(m) glucose phosphorylation is also required to signal
      glucose-stimulated genes affecting insulin release.

PMID- 9513085
TI  - High-level expression of biologically active recombinant bovine follicle
      stimulating hormone in a baculovirus system.
AB  - Superovulation treatment of cows can benefit from the application of very pure
      recombinant bovine FSH (rbFSH), which is produced in nonmammalian cells. rbFSH is
      completely free of LH, and therefore can possibly reduce the variability in the
      results of superovulation. Furthermore, it does not contain brain-tissue-derived
      proteins and, when produced under serum-free conditions, it is free of other
      mammalian substances or potentially infectious material. We have produced rbFSH
      in insect cells, with the ultimate aim of inducing superovulation in cattle. Sf21
      insect cells were coinfected with two recombinant baculoviruses, containing the
      cDNAs of bovine FSH alpha- and beta-subunits respectively. High levels of
      production of bioactive rbFSH were obtained after cloning cDNA that contained a
      major part of the 3' untranslated region of the bFSH beta gene. Maximum
      production of rbFSH 1-5 micrograms/ml (as measured by immunoassay) was obtained
      70-90 h after infection. The recombinant material was highly potent in two in
      vitro bioassays, giving biological activities of 13 IU/ml (Y1 cell rounding
      assay), 22 IU/ml (Y1 cell cAMP assay), and 23 IU/ml (bovine oocyte maturation
      inhibition assay), and had a lower but significant activity of 6 IU/ml in the rat
      Sertoli cell assay. rbFSH was purified by immunoaffinity chromatography, using a
      monoclonal antibody directed against the human FSH beta-subunit. The purified
      heterodimer appeared to be homogeneous by SDS-PAGE, whereas the free beta-subunit
      appeared as a doublet, possibly indicating differently glycosylated forms. Intact
      heterodimer and both subunits were further identified by western blot analysis,
      and showed apparent molecular masses of 20 kDa (alpha-subunit), 23 kDa (beta
      subunit) and 32.5 kDa (heterodimer). This insect-cell-produced rbFSH did not bind
      to wheat germ agglutinin, thus indicating that glycosidic side-chains may not
      contain terminal sialic acid. The relevance of a large 3' untranslated region in
      bFSH beta cDNA to the level of production of rbFSH, and the possible implications
      of the pattern of glycosylation for the biological activity of the recombinant
      hormone are discussed.

PMID- 9513086
TI  - Characterization of cDNAs encoding isoforms of hamster 3 beta-hydroxysteroid
      dehydrogenase/delta 5-->4 isomerase.
AB  - Western blot analyses of various hamster tissues reveal high levels of expression
      of 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) in adrenal and liver, and
      moderate levels of expression in kidney. The expression in liver is sexually
      dimorphic; very high levels of protein are observed in adult male liver but very
      low levels are seen in the female liver. Three distinct cDNAs encoding isoforms
      of 3 beta-HSD were isolated from hamster cDNA libraries. The type 1 isoform is a
      high-affinity dehydrogenase/isomerase expressed in adrenal and male kidney. The
      type 2 isoform is also a high-affinity dehydrogenase/isomerase expressed in
      kidney and male liver. The type 3 enzyme is a 3-ketosteroid reductase expressed
      predominantly in kidney. Sequencing of the clones showed that all three are
      structurally very similar, although types 1 and 2 share the greatest degree of
      similarity. Immunohistochemical staining for 3 beta-HSD in the adrenal was found
      throughout the adrenal cortex. In the kidney staining was confined to tubules,
      and in the liver, heavy staining was found in hepatocytes. The cloning of cDNAs
      for 3 beta-HSD from the liver and kidney should help in elucidating the function
      of this enzyme in these tissues.

PMID- 9513087
TI  - The effect of the peroxisome proliferator ciprofibrate on the gastric mucosa and
      particularly the gastrin cell.
AB  - The peroxisome proliferator ciprofibrate induces hypergastrinemia without
      inhibiting acid secretion. The present study was carried out to assess the effect
      of ciprofibrate on serum gastrin and gastrin (G) cells in different strains of
      rats and to compare the effect of ciprofibrate with other lipid-reducing agents
      (lovastatin and simvastatin) which have a different mechanism of action. Serum
      gastrin was determined by a radioimmunoassay method, G cell density by
      histomorphometry after immunostaining for G cells, and gastrin, somatostatin and
      histidine decarboxylase (HDC) mRNA abundance by Northern blot analysis.
      Ciprofibrate (100 mg/kg/day for three weeks) induced a marked hypergastrinemia (P
      < 0.01) in male and female Fischer rats as well as in female Wistar rats.
      Simvastatin and lovastatin did not affect serum gastrin. Antral G cell density
      increased significantly in female Wistar rats (P < 0.05) and non-significantly in
      the other rats after ciprofibrate. Both gastrin and somatostatin mRNA abundance
      in antral mucosa increased markedly and significantly (P < 0.01) after
      ciprofibrate treatment. The present study shows that the peroxisome proliferator
      ciprofibrate induces hypergastrinemia secondary to an increased storage and
      synthesis of antral gastrin. Since somatostatin mRNA abundance also increased,
      the present study suggests that ciprofibrate and possibly other peroxisome
      proliferators in sufficient concentrations have a stimulatory effect on endocrine
      cells.

PMID- 9513088
TI  - Gene expression of luteinizing hormone receptor and steroidogenic enzymes during
      Leydig cell development.
AB  - Testicular Leydig cells (LC) are rapidly and selectively destroyed by an
      injection of ethane dimethane sulfonate (EDS). LC regeneration occurs in the
      testis of the EDS-treated rats from the differentiation of the precursor Leydig
      cells (PLC). This study was designed to investigate the patterns of change in the
      mRNAs for the luteinizing hormone receptor (LHR) and the steroidogenic enzymes,
      cholesterol side chain cleavage (P-450scc) and 17 alpha-hydroxylase (P-450(17
      alpha)) during LC regeneration from PLCs. Mature (60 days of age) Sprague-Dawley
      male rats received a single intraperitoneal injection of EDS and were killed at
      different times between days 2 and 60 post-treatment. PLC- and LC-enriched
      fractions were isolated from the testes of the EDS-treated rats and age-matched
      control rats using a collagenase digestion-Percoll gradient method. Total RNA was
      extracted from these cell populations and subjected to Northern blot analysis.
      The LC fraction isolated from testes of control rats expressed four major
      transcripts of the LHR, sized 1.8, 2.5, 4.2 and 7.0 kb. The undifferentiated PLC
      fraction from controls expressed only a truncated form, the 1.8 kb transcript.
      This truncated LHR transcript was also the only LHR mRNA species detected in PLCs
      at day 2 post-EDS treatment. In contrast, all four transcripts of the LHR were
      detected in the PLC fraction at day 10 post-EDS treatment. The levels of the full
      length 7.0 kb transcript increased thereafter and reached a peak between days 24
      and 36 post-EDS treatment in the PLC fraction. Concomitant with the increase in
      the 7.0 kb transcript, the truncated 1.8 kb transcript decreased in amount and
      reached a nadir between days 16 and 36 post-treatment. The changes observed in
      this cell fraction reflect the process of differentiation of PLCs into LCs. At
      day 45 post-EDS treatment, the level of the 7.0 kb transcript decreased while the
      1.8 kb form increased in the PLC fraction, reflecting the completion of LC
      regeneration from this cell fraction. By day 60 post-EDS treatment, the levels of
      the 1.8 kb transcript rose to the value observed in undifferentiated control PLCs
      and the other transcripts were no longer detected in the PLC fraction, indicating
      that cells in the PLC fraction were again in an undifferentiated stage. Messenger
      RNAs for both the steroidogenic enzymes, P-450scc and P-450(17 alpha) were
      expressed in the control LC fraction. Neither of these two mRNAs were detected in
      the PLC fraction of the control rats. P-450scc and P-450(17 alpha) mRNAs were
      first expressed in the PLC fraction at day 10 post-EDS treatment. Thereafter, the
      levels of P-450scc and P-450(17 alpha) mRNAs increased in the PLC fraction and
      reached a peak between days 24 and 36 and days 24 and 45 post-EDS treatment
      respectively. P-450scc and P-450(17 alpha) mRNAs were no longer expressed in the
      PLC fraction at day 60 post-EDS treatment. These patterns also reflect the
      process of differentiation of PLCs into functional LCs. These results demonstrate
      for the first time that PLCs in the control testis are undifferentiated and do
      not express functional LHR and steroidogenic enzymes or their mRNAs. The PLCs are
      characterized, however, by the expression of a truncated 1.8 kb transcript of the
      LHR mRNA. Functional LHR and steroidogenic enzymes are expressed in PLCs only
      during their differentiation into LCs after EDS treatment. Subsequent to LC
      regeneration, the PLCs return to an undifferentiated stage.

PMID- 9513089
TI  - The analysis of regulatory sequences required for high level induction of rat
      alpha 2u-globulin gene expression by dexamethasone.
AB  - The alpha 2u-globulins are the major urinary proteins in adult male rats. They
      are encoded by a gene family, the expression of which is under multihormonal
      control in the liver. Glucocorticoids are positive regulatory hormones and we
      have analyzed the contribution of 5'-upstream sequences to the induction by
      dexamethasone of two cloned members of the family transfected into mouse L-cells.
      The results demonstrate that sequences from -762 bp to -226 bp of clone 91 are
      required for the 24-fold level of induction that was observed. Addition of 5.5 kb
      of upstream sequence beyond -762 bp did not alter the level of induction
      significantly, whereas deletion of the DNA between -762 bp and -226 bp reduced
      inducibility to about 4-fold. Sequencing of this region revealed that an element,
      5'-AGAACAggtTTCAAA-3', similar to the 15 bp consensus glucocorticoid response
      element 5'-AGAACAnnnTGTACC-3', is situated 513 bp upstream of the transcription
      start site. We infer that this element or its left half site is necessary for the
      dexamethasone-induced expression of clone 91 from the observation that a second
      gene, clone 2, that contained a base substitution at position 5 in the left half
      site was not inducible. It now appears that at least three distinct cis-acting
      regulatory regions, all of which bind to the glucocorticoid receptor in vitro,
      may contribute to the full induction of clone 91 by dexamethasone. These are: the
      distal upstream region identified by this study, a proximal upstream region that
      binds not only the receptor but also alpha 2uNF1, a constitutively expressed
      nuclear protein required for induction and a region within the fourth intron that
      contains five tandem receptor binding sites.

PMID- 9513090
TI  - The induction by estrogen of rat alpha 2u-globulin gene expression in mouse L
      cells.
AB  - Expression of the rat alpha 2u-globulin gene family is regulated in the adult
      male liver by a number of hormones, including growth hormone, thyroid hormone and
      several steroids. Upon injection into ovariectomized females, estrogens first
      induce alpha 2u-globulin expression and then suppress this gene after several
      days of hormone administration. To study this phenomenon, we developed a mouse L
      cell line that expressed the human estrogen receptor. High levels of rat alpha 2u
      globulin transcript were induced in stable transfectants of this line carrying a
      cloned alpha 2u-globulin gene, following exposure to 17 beta-estradiol. Since
      this induction was inhibited by cycloheximide, the response to estrogen, as to
      other steroids, appears to be secondary. Using genes with variously deleted 5'
      upstream regions, sequences responsible for this induction were located between 
      730 bp and -223 bp relative to the start of transcription. Examination of the DNA
      in this region revealed that an estrogen receptor element was located at -590 bp
      in an area that is highly conserved in most known alpha 2u-globulin genes.
      Administration of both dexamethasone and estrogen produced a synergistic effect
      in this system. The induction of alpha 2u-globulin RNA by estrogen in L-cells may
      re-capitulate the initial response to estrogen in vivo, and therefore represents
      a good model system to seek the identity of the other factors required to effect
      full induction.

PMID- 9513091
TI  - Suppression subtractive hybridization (SSH) identifies prolactin stimulation of
      p38 MAP kinase gene expression in Nb2 T lymphoma cells: molecular cloning of rat
      p38 MAP kinase.
AB  - Suppression Subtractive Hybridization (SSH) has been used to compare rat Nb2
      cells treated with prolactin for 1 hour with untreated cells. This new method for
      identifying differentially expressed genes showed that the mRNAs for at least
      three genes were elevated by such treatment, including a p38 mitogen activated
      protein (MAP) kinase. The p38 MAP kinase was cloned and the full length cDNA
      sequence was determined.

PMID- 9513092
TI  - Growth inhibition of both MCF-7 and Hs578T human breast cancer cell lines by
      vitamin D analogues is associated with increased expression of insulin-like
      growth factor binding protein-3.
AB  - The effects of two vitamin D analogues, EB1089 and CB1093, on insulin-like growth
      factor binding protein (IGFBP) expression have been examined in MCF-7 and Hs578T
      human breast cancer cell lines. Both vitamin D analogues inhibited IGF-1
      stimulated growth of MCF-7 cells and enhanced the production of IGFBP-3 as
      determined by Western-ligand blotting. Recombinant human IGFBP-3 inhibited the
      growth of MCF-7 cells over the concentration range 1-235 ng/ml. Hs578T cells were
      unresponsive to the mitogenic effects of IGF-1 but growth was inhibited by the
      two vitamin D analogues. Treatment of Hs578T cells with EB1089 and CB1093 (10 nM)
      as well as 100 nM 9-cis retinoic acid (9-cis RA) or all-trans retinoic acid
      (ATRA) was associated with increased accumulation of IGFBP-3 in conditioned
      medium. Furthermore, cotreatment of Hs578T cells with EB1089 and 9-cis RA led to
      augmented effects on both inhibition of cell growth and IGFBP-3 accumulation in
      conditioned medium as assessed by Western ligand blotting and radioimmunoassay.
      These findings suggest a role for IGFBP-3 in the growth inhibitory effects of
      vitamin D analogues.

PMID- 9513093
TI  - Esthetic, biologic and restorative considerations in coronal segment reattachment
      for a fractured tooth: a clinical report.
AB  - Reattachment of a fractured clinical crown involving minimal invasion of the
      biologic width can be accomplished without conventional ostectomy and crown
      lengthening so that satisfactory esthetics can be achieved. Adhesive techniques
      sometimes in conjunction with traditional mechanical retention, such as a post,
      can be used to reattach the fractured segment. An esthetic result can be obtained
      with a minimal number of procedures and cost to the patient.

PMID- 9513094
TI  - Double-casting method for fixed prosthodontics with functionally generated path.
AB  - STATEMENT OF PROBLEM: The construction of precise fixed prostheses that are
      harmonious within the stomatognathic function has been regarded as a critical
      requirement for successful oral rehabilitation. However, techniques for
      construction have been unsuccessful in producing a prosthesis that can be
      inserted without intraoral occlusal adjustment. PURPOSE: In this study, a new
      method of constructing a precise prosthesis that requires limited occlusal
      adjustment at the final seating is described. MATERIAL AND METHODS: The precision
      of this method was compared with a conventional method. Fourteen artificial
      crowns were fabricated on an experimental abutment by using both double-casting
      and conventional methods. The distances between the cusp tips and occlusal
      surfaces of the abutments, which were measured on wax/resin patterns and
      resultant crowns, were recorded to estimate clinical error for each method.
      RESULTS: Error for the double-casting method was markedly less than the
      conventional method. This study demonstrated that a new double-casting method was
      precise and sufficiently reliable for clinical application.

PMID- 9513095
TI  - The effect of glass fiber reinforcement on the fracture resistance of a
      provisional fixed partial denture.
AB  - PURPOSE: This study determined the load required to fracture a three-unit
      provisional fixed partial denture restoration, which had been reinforced with an
      experimental glass fiber reinforcement. MATERIAL AND METHODS: Provisional fixed
      partial dentures (n = 5) were fabricated from a resin of polyethyl methacrylate
      powder and n-butylmethacrylate liquid. The fixed partial dentures in the control
      group were unreinforced. In the other groups, the fixed partial dentures were
      reinforced either with one, two, or three unidirectional glass fiber
      reinforcements and one glass fiber weave reinforcement. The load was applied to
      the fixed partial dentures by a steel ball placed in the cavity in the middle
      fossa of the pontic tooth. A longitudinal section of the fixed partial denture
      was made to determine the position of the reinforcements. Means were compared by
      analysis of variance. RESULTS: The load required to fracture the unreinforced
      fixed partial denture was 614 N, while incorporation of one unidirectional
      reinforcement increased the load to 660 N, two reinforcements to 818 N, three
      reinforcements to 827 N, and three reinforcements with one weave reinforcement to
      973 N. It was found that the unidirectional reinforcements were positioned on the
      side of the occlusal surface of the fixed partial denture, namely, the side of
      compression during loading. CONCLUSION: The results suggest that, even though the
      glass fiber reinforcements were positioned on the least favorable side of the
      fixed partial denture in terms of the physical properties of the materials, these
      reinforcements considerably increased the fracture resistance of the provisional
      fixed partial denture.

PMID- 9513096
TI  - Sealing ability of two "compomers" applied with and without phosphoric acid
      treatment for Class V restorations in vivo.
AB  - STATEMENT OF PROBLEM: "Compomers" are being used with increasing frequency in
      Europe and North America. PURPOSE: This study evaluated the marginal seal of two
      compomers in vivo. MATERIAL AND METHODS: Periodontally involved teeth, scheduled
      for extraction, were selected. Four groups of a combination of materials were
      used (Dyract with Dyract-PSA primer, group 1; Dyract with Prime and Bond 2.0,
      group 2; Compoglass with SCA primer, group 3; and Compoglass with Syntac Single
      Component, group 4). The restorations were made in a standardized shaped cavity,
      across the cementoenamel junction, and the teeth were extracted after 2 to 3
      months of clinical service. The specimens were kept in a solution of 2% methylene
      blue for 24 hours. After being embedded in epoxy resin, sections were made with a
      low speed saw along the longitudinal axis of the teeth. The examination of dye
      penetration was made with a microscope at a magnification of x20 and scoring was
      done at both coronal and apical sites. Kruskal-Wallis statistical analysis was
      performed at 5% significance level. RESULTS: Groups 2 and 4 scored significantly
      less than groups 1 and 3 and for groups 2 and 4, 30% of the restorations
      exhibited leakage. CONCLUSION: These restoration systems did not completely
      prevent leakage either at the incisal or the cervical margins. Therefore the use
      of an enamel-dentin bonding system in combination with the proprietary compomer
      is recommended.

PMID- 9513097
TI  - Long-term monitoring of microleakage of cavity varnish and adhesive resin with
      amalgam.
AB  - STATEMENT OF PROBLEM: The penetration of oral fluids and bacteria at the
      interface between the cavity walls and amalgam restorations, which is known as
      marginal leakage, is one of the problems facing restorative dentistry today. This
      may cause secondary caries and the irritation of the pulp. PURPOSE: This in vitro
      study tested and compared the sealing ability of a cavity varnish and a dental
      adhesive for decreasing the marginal leakage of high copper amalgam fillings by
      chemical diffusion technique. MATERIAL AND METHODS: The samples were randomly
      divided into three groups. The cavities in the first group were filled with high
      copper amalgam. In the second and third groups, the cavities were treated with
      Copalite and Panavia EX adhesives, respectively, before the amalgam fillings were
      performed. After the periods of 2 hours, 48 hours, 1 week, and 1.5 and 6 months,
      the amount of calcium diffused through the interface area into the deionized
      water was measured with inductively coupled plasma. RESULTS: Six-month results
      revealed that using a dental adhesive as an interfacial sealer had significant
      advantages to reduce microleakage when compared with a conventional copal
      varnish.

PMID- 9513098
TI  - Efficacy of tray adhesives for the adhesion of elastomer rubber impression
      materials to impression modeling plastics for border molding.
AB  - STATEMENT OF PROBLEM: Tray adhesive, which is used for the adhesion of elastomer
      rubber impression materials to a custom resin tray, lowers the retention of the
      impression materials to the impression modeling plastics, as some ingredients of
      tray adhesive make the impression modeling plastic soft and tacky. PURPOSE: The
      efficacy of tray adhesive, which is used for the adhesion of elastomer rubber
      impression materials to a custom resin tray, on the adhesion between elastomer
      rubber impression material and impression modeling plastic was investigated.
      MATERIAL AND METHODS: Four silicone rubber impression materials (two addition
      reaction types and two condensation reaction types), two polysulfide rubber
      impression materials, and one impression modeling plastic were used in this
      study. Tensile strength between elastomer rubber impression material and
      impression modeling plastic with or without the application of tray adhesive was
      evaluated. RESULTS: Although tray adhesives for both addition reaction type and
      both condensation reaction type of silicone impression materials and one tray
      adhesive for polysulfide rubber impression material increased the tensile
      strength between the impression material and impression modeling plastic, one
      tray adhesive for polysulfide rubber impression material decreased the tensile
      strength when sufficient drying time was not applied.

PMID- 9513099
TI  - Clinical wear study of three commercially available artificial tooth materials:
      thirty-six month results.
AB  - STATEMENT OF PROBLEM: Excessive wear of artificial resin teeth has been a concern
      to both the patient and the dentist because of unfavorable associated sequelae.
      The search for a more wear resistant resin tooth material resulted in the
      development of modified resin teeth that displayed acceptable wear resistance.
      PURPOSE: This study compared clinical wear of a new modified resin tooth material
      with two other commercially available modified resin materials over a period of
      36 months. Differences in wear by gender, cuspal anatomy, arch, individual tooth
      type, and chewing side preference were also evaluated. MATERIAL AND METHODS: A
      total of 67 patients were randomized into one of three treatment groups in this
      double-blind study; group 1, Ivoclar-Vivodent and Orthotyp; group 2, Dentsply
      Trublend SLM; and group 3, Dentsply-Bioblend IPN. Tooth wear was determined by
      measuring vertical heights of contacting points at baseline and 36 months with a
      computerized coordinate measuring machine and computer-controlled positioning
      stages. Measurements were completed at 36 months for 55 patients who remained in
      the study. RESULTS: Repeated measures analysis of variance revealed no
      significant difference in total wear by gender or tooth material at 36 months.
      There was also no significant difference by chewing side preference or cuspal
      anatomy. However, there was a significant difference in individual tooth wear
      (canine, premolar, molar) and by arch. CONCLUSION: New modified resin teeth have
      displayed clinically acceptable wear resistance for most patients.

PMID- 9513100
TI  - In vitro wear of resin denture teeth.
AB  - STATEMENT OF PROBLEM: One of the most important physical properties of artificial
      teeth used in the restoration of the edentulous patient is wear resistance, and
      the ability of these teeth to maintain a stable occlusal relationship over time.
      PURPOSE: This study compared the in vitro wear of four different resin denture
      teeth against human enamel. MATERIAL AND METHODS: Five denture tooth samples
      opposing five enamel abraders were positioned in a mechanical wear testing device
      for two 5,000 cycle wear periods (total of 10,000 cycles) under a 13.4 N load.
      All tests were conducted in human saliva, and the wear was measured at the end of
      each test period. RESULTS: The wear of the Classic and Kenson acrylic resin
      denture teeth was much greater than the DB Plus and MLI composite teeth after
      10,000 cycles. The wear of the KENSON denture tooth was also greater than the
      Classic tooth. No wear differences were found between the two composite teeth.
      CONCLUSIONS: The wear of DB Plus and MLI resin denture teeth was approximately
      50% less than the wear of Classic and Kenson teeth when opposed by human enamel.

PMID- 9513101
TI  - Rigidly splinted implants in the resorbed maxilla to retain a hinging
      overdenture: a series of clinical reports for up to 4 years.
AB  - STATEMENT OF PROBLEM: The results of the implant overdenture treatment in the
      maxilla remains inferior to those in the mandible. Different reasons have been
      alluded to, such as bone quality and quantity, number of implants, as well as the
      prosthesis design. PURPOSE: To investigate the latter, a new design for the
      rehabilitation of the resorbed maxillae was set up. MATERIAL AND METHODS:
      Thirteen patients were selected and provided with four endosseous maxillary
      implants, splinted with a rigid-cast bar. RESULTS: After a mean loading time of 3
      years, six implants were lost; three at abutment and another three shortly after
      abutment connection, resulting in a cumulative success rate of 88.6% at year 4. A
      mean marginal bone loss of 0.3 mm was observed within the first year. After the
      first year, the marginal bone level, the attachment level, and the Periotest
      scores hardly changed. The main prosthetic complication was the frequent need to
      renew or to activate the attachments. A strong improvement in patient
      satisfaction was observed when compared with the old conventional denture.
      CONCLUSIONS: Within the limits of this study, the outcome confirmed that, on a
      medium-term base, implant-retained hinging overdentures on four implants were
      promising.

PMID- 9513102
TI  - A pilot study comparing the efficacy of hard and soft stabilizing appliances in
      treating patients with temporomandibular disorders.
AB  - STATEMENT OF PROBLEM: Soft and hard stabilizing appliances have been used to
      treat temporomandibular disorders. No data exist to suggest whether a hard or
      soft appliance is beneficial. PURPOSE: This study compared soft and hard acrylic
      resin stabilizing appliances in the reduction of masticatory muscle pain in
      patients with temporomandibular disorders. MATERIALS AND METHODS: Twenty-three
      patients with at least one clinical sign from the list of diagnostic subgroups of
      temporomandibular disorders were alternately assigned a hard or soft appliance
      for temporomandibular disorder treatment. No other temporomandibular disorder
      treatment (self-care, physical therapy, biofeedback, or muscle or joint
      injections) was rendered. Each patient was seen by two dentists at each visit.
      One dentist initially fabricated the appliance and adjusted the appliance on each
      visit and an examining dentist examined the patient each visit and recorded signs
      of temporomandibular disorders. The appliance material (soft or hard) was not
      disclosed to the examining dentist, only to the dentist who fabricated and
      adjusted the appliance. Patients were examined and appliances were adjusted every
      2 to 3 weeks for a minimum of 10 weeks. Masticatory muscles were palpated and
      charted on each visit. Data were analyzed and subjected to nonparametric Mann
      Whitney test. RESULTS: Eighteen of the initial 23 patients, 7 in the hard
      appliance group and 11 in the soft appliance group finished the study over 10- to
      15-week period. Soft and hard appliances performed the same in reduction of
      masticatory muscle pain. CONCLUSION: This study suggests, based on the limited
      number of participants, that soft and hard stabilizing appliances may be equally
      useful in reducing masticatory muscle pain in short-term appliance therapy.

PMID- 9513103
TI  - A scanning electron microscopic study of tooth surface changes induced by tannic
      acid.
AB  - STATEMENT OF PROBLEM: Exposing the tooth structure to chemicals used in
      displacing the gingival tissue is inevitable. PURPOSE: This study was undertaken
      to microscopically examine the effect of tannic acid on the prepared dentin
      surface. MATERIAL AND METHODS: Forty recently extracted intact human teeth were
      mounted for buccal surface preparation. Teeth were equally divided into 10
      groups. One group was kept as a control and the other teeth received a topical
      application of 15%, 20%, and 25% aqueous tannic acid solutions each for 5, 10,
      and 15 minutes at room temperature. All samples were washed, air-dried, then
      prepared for scanning electron microscopic examination. Two different areas in
      the cervical region were randomly selected and examined under magnifications of
      x1000 and x2000, then photographed. The assessment of the changes was performed
      qualitatively. RESULTS: The results showed an incomplete removal of the smear
      layer in all experimental samples. The astringent action of the tannic acid
      solution on both the smear layer and the surface peritubular dentin around the
      orifices of dentinal tubules had contributed to their constriction. The degree of
      constriction of the orifices of dentinal tubules increased as higher
      concentrations of tannic acid solutions were used and as the application time was
      further increased at each concentration. CONCLUSION: The tannic acid had an
      incomplete action on the removal of the smear layer. It also seemed to have an
      astringent action on both the smear layer and the peritubular dentin.

PMID- 9513104
TI  - Stress relaxation of heat-activated acrylic denture base resin in the mold after
      processing.
AB  - STATEMENT OF PROBLEM: Stress relaxation of polymethyl methacrylate has been
      reported, but no studies have investigated residual stress relaxation in heat
      activated acrylic denture base resin fabricated by the polymer-monomer mixture
      method. PURPOSE: This study evaluated the development of residual stress
      relaxation and clarified how restricted time in the stone mold influenced stress
      relaxation of heat-activated acrylic denture base resin after processing.
      MATERIAL AND METHODS: Flat, dumbbell-shaped specimens were used. Thermocouples
      and strain gauges were embedded in resin for measuring temperature and strain at
      the dough-stage of resin packing. To clarify the stress relaxation in the stone
      mold, specimens were removed from the mold by deflasking at 4 hours after from
      the start of bench cooling (immediately after reaching room temperature;
      control), and 1 day, 3, 5, and 10 days from the start of bench cooling. RESULTS:
      Shrinkage strains at deflasking were two thirds for 1 day restriction, one half
      for 3 and 5 days restriction, as compared with the control. CONCLUSIONS: This
      study suggested that removing a denture base fabricated by heat-activated acrylic
      denture base resin from the stone mold only after keeping it in stone mold for at
      least 1 day or more was effective for reducing deformation of the denture base.

PMID- 9513105
TI  - Adhesion and tear energy of a long-term soft lining material activated by rapid
      microwave energy.
AB  - STATEMENT OF PROBLEM: Construction of dentures with permanent soft linings is
      time-consuming in the laboratory and extra costs are related to equipment and
      materials used. PURPOSE: The purpose of this in vitro study was to determine
      whether using microwave energy to activate the polymerization of a silicone
      rubber denture soft lining material affected its properties. MATERIAL AND
      METHODS: Tear energy and adhesive properties were measured in a tensile testing
      machine by using a pants leg tear test and peel specimens. Tear energy was
      measured for specimens polymerized conventionally (control) and for 3, 5, and 10
      minutes in a microwave. Data were analyzed with one-way analysis of variance and
      a two-sample Student t test. RESULTS: The multiple comparison test failed to show
      a significant difference in tear energy between 3 minutes microwave activation
      and conventional heat curing. However, 3 minutes microwave activation revealed a
      significantly stronger material when compared with 5 minutes and 10 minutes (p <
      0.05). Application of a two-sample Student t test failed to demonstrate a
      significant difference between microwave energy and conventional heat activation
      groups in the adhesion test. In adhesion testing, all specimens presented
      cohesive failure. CONCLUSIONS: This method of polymerization does not compromise
      the strength of a soft lining material and its adhesion to polymethyl
      methacrylate. This study suggests the use of 3 minutes 650 W microwave energy for
      processing a silicone soft lining material.

PMID- 9513106
TI  - Rheology of tissue conditioners.
AB  - STATEMENT OF PROBLEM: Tissue conditioners can be used to condition abused
      tissues, record functional impressions, make temporary relinings, and for other
      clinical applications, mainly because of their specific viscoelasticity. However,
      little information is available on the rheology of the materials, manipulation,
      and suitability for various clinical applications. PURPOSE: This study evaluated
      the gelation times, the viscoelastic properties after gelation of tissue
      conditioners, and the influence of the powder/liquid (P/L) ratio. MATERIAL AND
      METHODS: Ten tissue conditioners were used and gelation times were obtained with
      an oscillating rheometer. A series of stress relaxation tests were also conducted
      to evaluate the viscoelastic properties after gelation and the changes with the
      passage of time by means of Maxwell model analogies. RESULTS: Significant
      differences were found in the gelation times and flow properties after gelation
      among the materials mixed with the P/L ratios recommended by the manufacturers.
      The flow properties tended to increase with time of storage. Large differences in
      the limits of the clinically acceptable P/L ratios and the adjustable limits of
      elasticity and viscosity by altering P/L ratios were found among the materials.
      CONCLUSIONS: The results suggested that each material should be selected
      according to each clinical purpose because of the wide ranges of viscoelastic
      properties and changes in viscoelasticity with time among the materials.
      Furthermore, gelation times and the viscoelastic properties after gelation can be
      controlled to improve handling and suit various applications by altering the P/L
      ratios within the acceptable limits.

PMID- 9513107
TI  - Comparison of the new matrix system with traditional fixed prosthodontic
      impression procedures.
AB  - This article compares the methods and effectiveness of traditional fixed partial
      denture impression systems, which includes the matrix impression system, in
      relation to the registration of the finish lines and sulci of tooth preparations
      in the formation of a full arch impression. Concepts relating to custom trays,
      retraction, homeostasis, sulcular cleansing, sulcular flange registration,
      configuration and strength, viscosity of elastomeric impression materials, and
      delivering the impression material into the sulcus are reviewed. Several concepts
      are questioned and alternative procedures are proposed. Forces that impact the
      gingival tissues and determine the success of the impression are briefly
      described.

PMID- 9513108
TI  - The matrix impression system for fixed prosthodontics.
AB  - This article describes the instrumentation, materials, and clinical procedures
      for the matrix impression system. The matrix impression system uses a custom
      matrix to control the sulcular environment and to deliver impression material to
      the subgingival parts to be impressed. It describes the four types of forces
      involved in gingival displacement during impressions, effective delivery of
      impression material with simultaneous sulcular cleansing, and simplification of
      complex impressions with or without segmentation. The application of the matrix
      impression system is described for making routine impressions and for some
      atypical problems. The article also provides a detailed description of the
      formation and design of the matrix.

PMID- 9513109
TI  - A minimally invasive second-stage procedure for single-tooth implants.
AB  - The natural look of dental restorations has become a universally claimed
      treatment objective, especially when single-tooth gaps are restored with
      implants. A harmonious gingival margin is crucial to achieve this goal. This
      article presents a new procedure for exposure of single-tooth implants that
      yields a favorable esthetic result in the visible maxillary regions because of
      the simple type of incision used. The procedure consists of two incisions: the
      first incision makes it possible to find out the implant position and the second
      incision shapes the mucous membrane according to local supply. The second
      incision also prevents the soft tissue from tearing after careful stretching and
      subsequent pressing of the supraimplant mucosa. There is minimal soft tissue
      traumatization, and as a result, healing time can be reduced to 1 week and an
      appealing esthetic result can be reached.

PMID- 9513110
TI  - A procedure for making an interocclusal record without the use of record bases
      for a combined fixed/removable prosthesis.
AB  - This article describes a procedure for making an interocclusal record for a
      remount procedure after tryin of the castings. This method can also be used for
      the initial mounting by substituting autopolymerizing acrylic resin copings for
      the metal castings.

PMID- 9513111
TI  - Four uses of a disposable implant mount.
AB  - The high cost of precision-fitting, machine-milled implant components is a major
      concern, and the dentist with a busy implant practice must stock numerous
      components at considerable expense. In this article, the use of a disposable
      implant mount is described as an adjunct for a positional index during stage-I
      surgery, immediate provisional restoration at stage-II surgery, verification jig,
      and implant-supported record base. By reusing the precision-fitting implant mount
      that is supplied free of charge by the manufacturer, the dentist can reduce the
      overhead costs required to provide implant prosthodontic treatment.

PMID- 9513112
TI  - An intraoral positioning appliance for stereotactic radiotherapy.
AB  - Stereotactic radiotherapy provides the most accurate and effective therapy and
      protects the adjacent, normal tissues. The head must be positioned the same for
      all treatments. This article describes the fabrication and application of a
      noninvasive intraoral appliance that verifies the position of the head to deliver
      more accurate radiotherapy and protect the adjacent, normal tissues.

PMID- 9513113
TI  - Fabrication procedure for cranial prostheses.
AB  - A procedure for duplication of cranial bone flaps used in cranioplasty is
      described. This procedure overcomes the difficulties inherent in direct
      duplication of irregular-shaped bone flaps through primary replication of the
      flap in wax. The wax pattern is used to fabricate the definitive prosthesis.

PMID- 9513114
TI  - A laboratory procedure to facilitate development of an emergence profile with a
      custom implant abutment.

PMID- 9513115
TI  - A simple method for maintaining retrievability of occlusal screws when the access
      channel is shallow.

PMID- 9513116
TI  - Fabrication of an acrylic resin record base with a gauze matrix.

PMID- 9513117
TI  - Use of an impression syringe with chairside relining materials.

PMID- 9513118
TI  - A new and easy method of stabilizing casts with cyanoacrylate.

PMID- 9513119
TI  - A method to simplify cleaning of a water bath pan.

PMID- 9513120
TI  - Interracial psychotherapy: a report of the treatment of an inner-city adolescent.
AB  - This report demonstrates the effectiveness of long-term psychodynamic
      psychotherapy between a patient and therapist of different races. The patient's
      experience as a member of a minority was recognized, as were the psychodynamic
      meanings that race possessed in reference to identification, transference,
      resistance, and countertransference.

PMID- 9513121
TI  - The relationship of patients' pretreatment representations of mother to early
      treatment representations of their therapist.

PMID- 9513122
TI  - Perspectivism, constructivism, and empathy in psychoanalysis: Nietzsche and
      Kohut.

PMID- 9513123
TI  - Using the Rorschach to define differences in schizophrenics and the implications
      for treatment.

PMID- 9513124
TI  - The transference refracted through the lens of attachment.

PMID- 9513125
TI  - Projective identification: some clinical considerations.
AB  - The projective identification situation is the essence of much of the analytic
      relationship and can either create a fluid unfolding between patient and analyst
      leading to structural change, or can lead to the limitation and subsequent
      eradication of the analytic relationship. Projective identification encompasses
      and defines the entire transference state and is often the chief resistance.
      Therefore, unless projective identification is understood and analyzed as a
      fundamental element in the relationship, an interminable state of enactment and
      confusion can take over and at times terminate the analytic journey. By the
      mutual exploration of projective identification situations, the relationship can
      be freed from potential limitations and constrictions and the analysis can
      naturally proceed.

PMID- 9513126
TI  - The import and export of psychoanalysis: India.

PMID- 9513127
TI  - Vengeance and transformation in Daniel Deronda.

PMID- 9513129
TI  - Psychoanalysis: a forum, a treatment, a profession.

PMID- 9513128
TI  - Remembrance of incarnations past: a Hindu case study.

PMID- 9513130
TI  - From mechanism to metaphor--on Freud's struggle with the biology of the mind.

PMID- 9513131
TI  - Nurses and assisted dying: taking our roles to heart and mind.

PMID- 9513132
TI  - End-of-life issues: a survey of English-speaking Canadian nurses in AIDS care.
AB  - This anonymous postal survey explored attitudes and experiences concerning end-of
      life decisions. Respondents were English-speaking members of the Canadian
      Association for Nurses in AIDS Care (CANAC) and other nurses identified as
      working primarily in HIV/AIDS settings. Seventy-three percent believed that the
      law should be changed to allow physicians to practice voluntary euthanasia (VE)
      and assisted suicide (AS). Fifty-three percent indicated that nurses should be
      allowed to practice VE and AS. Although VE and AS are illegal, fewer than one in
      five nurses would report a colleague whom they knew to be involved in such acts.
      More than one in five nurses have received requests from patients to hasten their
      deaths by VE. Nearly 98% believe that the nursing profession should be involved
      in policy development concerning VE and AS, and nearly 78% believe that nurses
      should be involved in the decision-making process with patients if such acts were
      legal. Given that ethical codes for Canadian nurses promote client self
      determination and that nurses are the largest group of care providers for the
      terminally ill, the profession must promote discussion and research if it is to
      take a leadership role with respect to end-of-life issues.

PMID- 9513133
TI  - Nurses' attitudes and beliefs toward assisted suicide in AIDS.
AB  - This report of a 1995 survey presents data regarding nurses' attitudes and
      beliefs about assisted suicide in AIDS. The authors surveyed 428 nurses working
      at facilities serving AIDS patients in the San Francisco Bay Area, using an
      anonymous, self-administered questionnaire. They received 215 responses (50%).
      There was a high level of agreement with statements that place assisted suicide
      in the context of humane action to relieve suffering. An AIDS diagnosis did not
      change respondents' attitudes toward assisted suicide, although many nurses said
      that the relentless suffering and specific nature of the AIDS epidemic did
      influence their thinking.

PMID- 9513134
TI  - Historical, ethical, and legal aspects of assisted suicide.
AB  - This article explores the historical, ethical, and legal antecedents of assisted
      suicide. Following a differentiation between assisted suicide and euthanasia, the
      historical aspects of suicide in the United States and other countries are
      described. Four cardinal principles form the basis for the ethical consideration
      of practice: autonomy, beneficence, nonmaleficence, and justice. Respect for
      autonomy is essential to the care of dying patients. However, the exercise of
      autonomy does not necessarily place an obligation to act on others. This could be
      important in the consideration of a request to a nurse for assistance in suicide.
      Nonmaleficence may also be a principle involved in decisions to discontinue
      treatments that are unwanted by the individual. Beneficence, the prevention of
      harm or the doing of good, may be in conflict with the respect for autonomy when
      one considers assisted suicide. Although one may wish to alleviate the suffering,
      assisting with death as a means of ending the suffering may violate the principle
      of beneficence even though the individual may, in his or her autonomy, request
      death. Justice describes what individuals are legitimately entitled to, but
      individual justice may be abridged by the utilitarian model of justice for
      society overall. Most states send ambivalent messages about the legal status of
      assisted suicide. Although many states criminalize assisted suicide, state
      prosecution of assisted suicide is not common. Furthermore, many juries have
      found those accused of murder or manslaughter in these instances "not guilty." A
      summary of the laws of each state related to assisted suicide is included.

PMID- 9513135
TI  - Palliative care.

PMID- 9513136
TI  - Is anybody listening? A phenomenological study of pain in hospitalized persons
      with AIDS.
AB  - Pain is a common problem among hospitalized persons with AIDS (PWAs), yet it has
      not been well studied. The purpose of this study was to understand, using the
      phenomenological method, the experience of pain in hospitalized PWAs. Multiple
      sources of data, including interviews with 11 hospitalized PWAs, literature,
      poetry, and film, were used to investigate the phenomenon. Five broad themes
      emerged: knowing pain, battling pain, having AIDS, pain's influence, and being a
      drug user. Multiple barriers to effective pain management were identified.
      Although there were commonalities in the experience of pain in chemically
      dependent and nonchemically dependent PWAs, unique challenges for the chemically
      dependent PWAs were identified. The findings indicate the importance of listening
      to and believing reports of pain. In addition, the findings underscore the
      delicate balance that exists between pain relief and relapse in PWAs with a
      history of chemical dependency.

PMID- 9513137
TI  - Oral mucosal transudate testing for HIV-1 antibodies: a clinical update.
AB  - The HIV epidemic and the social and clinical responses to it have changed
      dramatically in recent years in ways that significantly affect the nursing
      profession. In scope, the HIV epidemic has broadened demographically and
      geographically, shifting the burden of the epidemic and continuing to place
      stress on our health care and social service delivery systems. During the past 2
      years, there have been clinical advances in the ability to treat HIV disease as a
      more chronic, manageable condition, making it more important than ever for
      infected individuals to know their serostatus. A recently available HIV-1
      antibody test that uses oral mucosal transudate (OMT) fluid that compares
      favorably to serum in reliability, because it is based on the same enzyme-linked
      immunosorbent assay Western blot algorithm, has become available. The OMT test
      for HIV involves simple, safe, and non-invasive specimen collection that offers
      clinical and outreach advantages to nurses in AIDS care who provide counseling
      and testing.

PMID- 9513138
TI  - HIV-associated distal symmetrical polyneuropathy: clinical features and nursing
      management.
AB  - DSPN is a common manifestation of HIV infection and/or its treatment that can
      have adverse effects on quality of life and functional status. The pathogenesis
      remains unclear but likely involves the elaboration of neurotoxic inflammatory
      cytokines and their metabolites. DSPN is often refractory to available
      pharmacological treatments, although new treatments involving NGF hold promise
      for effecting sustained symptom relief and reversing axonal degeneration. Further
      research is needed to determine the efficacy of nonpharmacological treatments,
      such as cognitive-behavioral therapies, to alleviate DSPN-associated pain.

PMID- 9513139
TI  - HIV subterfuge.

PMID- 9513140
TI  - Should complex medication regimens be prescribed to people with a low probability
      of compliance?

PMID- 9513141
TI  - [New epidemics for the surveillance network].

PMID- 9513142
TI  - [Malarone: newcomer in the treatment of malaria].

PMID- 9513143
TI  - [Praziquantel].

PMID- 9513144
TI  - [Voyage to the land of ++Fiu].

PMID- 9513145
TI  - [Djibouti: dealing with a demographic explosion].

PMID- 9513146
TI  - [Imaging a tropical hydroureter].

PMID- 9513147
TI  - [Research and control of malaria or adopting easy solutions].

PMID- 9513148
TI  - [Research and malaria: from failure to hope].

PMID- 9513149
TI  - [Detection of trypanosomes in blood by the Quantitative Buffy Coat (QBC)
      technique: experimental evaluation].
AB  - Microhematocrit centrifugation (Woo test) and miniature anion exchange are the
      most widely used techniques for routine detection of Trypanosoma brucei gambiense
      in endemic areas. The QBC technique developed for diagnosis of malaria has been
      successfully used for detection of trypanosoma in blood. The purpose of this
      laboratory study was to evaluate the end-point sensitivity of the QBC test in
      comparison with the Woo test. Decreasing concentrations from 15 x 10(5) to 15
      trypanosomes/ml of human blood were tested using the two techniques. Sensitivity
      was calculated in function of reading time at each concentration. Results showed
      that the sensitivity of the QBC test was 95% down to a concentration of 450
      trypanosomes/ml. In comparison 95% sensitivity of the Woo test was observed only
      down to 7500 trypanosomes/ml and reading time was twofold longer. These findings
      were reproducible for two hours after sample preparation but deterioration was
      rapid thereafter. Given its simplicity and sensitivity, QBC test would appear to
      be a suitable technique for in-field screening programs for human African
      trypanosomiasis.

PMID- 9513150
TI  - [Inc J plasmids identified for the first time in Vibrio cholerae El Tor].
AB  - Two epidemic outbreaks of cholera occurred in eastern Algeria in 1994. Sixteen
      strains of Vibrio cholerae El Tor were isolated from stools and contaminated
      water. Studies to determine antibiotic sensitivity documented multiresistance in
      these strains. Minimal inhibiting concentrations ranged from 6 to 32
      micrograms/ml for chloramphenicol, from 8 to 24 micrograms/ml for tetracycline
      except minocycline, and from 15 to 32 micrograms/ml for furanes. Higher values
      were found for other antibiotics such as trimethoprime (1,500 micrograms/ml),
      streptomycine (128 micrograms/ml) and sulfamides (128 micrograms/ml). High-grade
      resistance of Vibrio cholerae El Tor to streptomycine and trimethoprime in
      association with resistance to 0:129 suggests that transposon is the underlying
      genetic factor. All resistance markers were located on a single structure that
      can be transferred to a Escherichia coli receptor and belongs to an Inc J
      incompatibility group. The fact that plasmid DNA could not be visualized on
      agarose gel after extraction is also evidence for a transferable transposon.

PMID- 9513151
TI  - [Malaria epidemic during a military-humanitarian mission in Africa].
AB  - A malaria epidemic broke out among French servicemen during a humanitarian
      military mission carried out in Central Africa in 1996. The purpose of this study
      was to determine compliance with drug prophylaxis for malaria by measuring blood
      levels of antimalarial drugs (combination treatment using chloroquine-proguanil
      or treatment with doxycycline) as well as to assess the conditions of vector
      control. The incidence density rate of malaria over a 60-day period was 3.1 cases
      per month per 100 men. Only reinforcement troops were affected. The risk of
      developing malaria was 5 times higher among new arrivals than in servicemen who
      had been in the zone for several months (95% CI relative risk = [2.9-7.8]). Type
      of prophylactic treatment had no effect on the incidence density rate. Study data
      showed that 40.2% of those treated for malaria were not in compliance with
      prophylactic treatment at the time of the malarial attack and that those who were
      in compliance with prophylaxis, i.e. the remaining 59.8%, presented a strain of
      plasmodium that was resistant to the prophylactic drugs at doses used. Findings
      also indicated the epidemic occurred mainly because operating conditions
      prevented implementation of proper vectorial control. The risk of epidemic could
      probably have been reduced by improving compliance with prophylactic treatment
      and changing standard vectorial control techniques, e.g. by using insecticide
      treated uniforms.

PMID- 9513152
TI  - [Frequency of Helicobacter pylori infection in symptomatic patients in Senegal].
AB  - This prospective study was carried out in Dakar, Senegal, to assess the
      prevalence of Helicobacter pylori infection in symptomatic patients undergoing
      endoscopy and to evaluate the factors of risk for infection by this type of
      bacteria in the population. From October to December 1995, 134 patients were
      included in this study and replied to a standardized questionnaire designed to
      determine socioeconomic level and living conditions. Diagnosis of Helicobacter
      pylori infection was based on the combined results of the urea breath test (Clo
      test) and histological findings. Helicobacter pylori infection was detected in
      82.8% of patients with no significant difference according to sex, age, ethnic
      group, or living environment (urban or rural). The incidence of infection was
      also the same in all socioeconomic groups. It was already high in the age group
      between 11 and 20 years (90.9%). Helicobacter pylori was identified in 76.2% of
      patients with normal endoscopic findings and in 100% presenting ulcers, erosions,
      or gastritis. This study shows that the incidence of Helicobacter pylori
      infection is extremely high regardless of socioeconomic level and that infection
      begins at a young age. These findings are consistent with the poor hygiene of
      most people in Senegal.

PMID- 9513153
TI  - [Cerebral toxoplasmosis and AIDS in Martinique].
AB  - This study was carried out in 60 AIDS patients who presented toxoplasma
      encephalitis in Martinique (French West Indies). Diagnosis was based on a
      combination of fever, neurologic signs, and characteristic CT-scan images in
      patients with positive HIV serology. There were 46 males and 14 females with a
      mean age of 40 years. The mode of transmission was heterosexual in most cases
      (68.3%). The incidence of drug-related transmission was low (6.7%).
      Neurotoxoplasmosis was the most frequent presenting symptom of AIDS (53.3%)
      followed by esophageal candidosis (20%) and pneumocystosis (10%). Clinical
      symptoms were headache (56.5%), fever (48.3%), hemiparesia (36.6%), and confusion
      (36.6%). CT-scan showed most lesions to be multiple (70%), hypodense (89%), and
      subject to contrast uptake (93%). Mean lymphocyte level was 1128/mm3 with 88
      CD4/mm3 and a CD4-to-CD8 ratio of 0.14. Conventional treatment using a
      combination of pyrimethamine and sulfadiazine led to skin rash and neutropenia
      and had to be discontinued in 30% of cases. Clinical symptoms and mean survival
      (327 days) were the same as comparable findings from Europe and North America.

PMID- 9513154
TI  - [Aseptic purulent meningitis in two patients co-infected by HTLV-1 and
      Strongyloides stercoralis].
AB  - Occurrence of anguilluliasis always progresses to hyperinfestation or
      disseminated anguilluliasis with severe clinical manifestations in carriers of
      HTLV-1. This prognosis is further illustrated by two new cases of non-septic
      purulent meningitis observed in two male patients from Guadalope. Ages were 61
      and 64 years. In both cases examination of cerebrospinal fluid (CSF) demonstrated
      pleiocytosis with more than 3000 cells (mostly polynuclear neutrophils) per mm3,
      protein content greater than 3 g/l, and low sugar level. No soluble germs or
      antigens were found in the CSF. In both patients Strongyloides stercoralis larvae
      were detected in stools but not in CSF. Meningitis responded to antibiotic
      treatment but follow-up tests showed the persistence of larvae in stools despite
      treatment using thiabendazole. While similar cases of meningitis have been
      reported in carriers of HTLV-1, the underlying mechanism is still unclear. Co
      infection with Strongyloides stercoralis appears to be a predisposing factor.
      This association may warrant preventive anti-parasitic treatment in patients
      infected by HTLV-1.

PMID- 9513155
TI  - [Redistribution of glossina in a forest area of Ivory Coast?].
AB  - Historically the region of Abengourou is a well-known of sleeping sickness in the
      forest area of Cote d'Ivoire. However data from epidemiologic studies carried out
      since 1980 show that this area is currently disease-free. This finding warrants
      study of glossina vectors to clarify the epidemiology of the disease in this
      area. Entomologic surveys were carried out over a period of one year. Traps were
      used to capture glossina in ten natural habitats: villages with or without pigs,
      coffee, cocoa and rice plantations, grazing lands, camping areas, uncultivated
      farmlands, trails, forest borderlands and wilderness. Findings documented almost
      total disappearance of zoophilic glossina (Glossina nigrofusca and Glossina
      pallicera) which accounted for less than 0.5% of glossina captured only during
      the rainy season. The apparent trap density (ATD) of Glossina palpalis, the main
      vector of disease, was low overall. However ATD values tended to be higher in
      villages with pigs (ATD : 2.07 glossina/trap/day) and forest borderlands (ATD :
      2.63 glossina/trap/day) than in other habitants where values were always lower
      than 1 glossina/trap/day. This almost complete disappearance of Glossina palpalis
      can be attributed mainly to deforestation in most of the areas studied. This
      accounts for reduced contact with man. The absence of contact between man and
      anthropophilic glossins could explain that unlike Daloa and Vavoua sleeping
      sickness has disappeared from the region of Abengourou.

PMID- 9513156
TI  - [Inflammatory pseudo-tumor of the liver in a child: case report].
AB  - Inflammatory pseudotumor of the liver is uncommon in children. Only 14 cases have
      been reported in the literature. The underlying etiology is unclear but traumatic
      and infectious factors may be implicated. This report describes an inflammatory
      pseudotumor that was observed in a 9-year-old child from the Ivory Coast one year
      after traumatic injury of the right hypochondrium. Clinical findings were limited
      to non-febrile but painful hepatomegaly with weight loss. Laboratory tests were
      consistent with an inflammatory process. Ultrasonography revealed a poorly
      delimited, heterogeneous area approximately 5 cm in diameter at the level of the
      VI segment which had been resected. Histology documented the presence of fibro
      inflammatory tissue with granulomatous inclusions. At the center of the lesion
      was a foreign body corresponding to a Schistosoma mansoni egg. In this case the
      mechanism underlying inflammatory pseudotumor could have involved either
      bilharziasis or trauma. A review of the literature allows the authors to
      enumerate the main features of this uncommon benign tumor of the liver in
      children.

PMID- 9513157
TI  - [Pediculated labial ureteroplasty: an original treatment procedure for ureteral
      lesions of obstetric origin].
AB  - Destruction of the urethra is the most severe complication of pregnancy-related
      vesicovaginal fistula. Although uncommon in Europe, pregnancy-related urethral
      destruction is still observed in Africa. In this study we describe our experience
      with a new reconstruction technique using a pedunculated skin flap raised from
      the labia majora. Between January 1992 and June 1996 we treated 35 patients in
      the Urology Department of Niamey Hospital in Niger. All patients were black. Mean
      age was 18 years and mean follow-up was 19 months. Two plasty techniques were
      used, i.e. extension (16 cases) and tubulisation (19 cases). Urinary incontinence
      was treated using a suburethral loop system created using a fatty flap taken from
      the labia majora (Martius method). Urethrocervico-suspension of the vagina was
      necessary in 6 cases. Normal micturition with no leakage was obtained in 24
      patients (68.6%) and functional improvement in 6 cases (17.1%) Treatment failed
      in 5 cases (4.2%). In comparison with previously reported techniques, urethral
      reconstruction using a pedunculated labial flap and suburethral looping system
      allows successful treatment of pregnancy-related urethral destruction in 70% of
      cases. This technique is particularly well suited for use in developing countries
      where occurrence of this complication is most frequent. However even with the
      greatest skill, creation of a physiologically perfect closure system is currently
      impossible.

PMID- 9513158
TI  - [Schistosoma intercalatum bilharziasis: clinical and epidemiological
      considerations].
AB  - Schistosoma intercalatum bilharziasis continues to raise numerous questions
      regarding pathogenicity and gravity. The parasite was identified recently and the
      last fully described outbreak occurred 10 years ago in the city of Bata,
      Equatorial Guinea. Geographically Schistosoma intercalatum biharziasis is limited
      to one part of the African continent but has shown a tendency to spread.
      Hybridization of Schistosoma intercalatum and Schistosoma haematobium has been
      observed. The main clinical manifestation of Schistosoma intercalatum is rectal
      bleeding. The endoscopic appearance of lesions is variable and non-specific
      ranging from granulomas or polyps to ulcerations. Complications include severe
      rectitis or genital involvement such as salpingitis with secondary sterility.
      Spontaneous abortion has also been reported. Association with salmonella and
      klebsiella infection has been confirmed and can lead to life-threatening
      situations. Few studies have been performed to assess the value of diagnostic
      tests. The sensitivity of stool smears and urinary sedimentation testing is 81.7%
      and 56.3% respectively using the two examinations as references for one another.
      The sensitivity of immunological tests is generally good but varies depending on
      the reference technique used. Specificity can be affected by cross-reaction with
      other schistosomas or trematodes and even with nematodes and hematozoons.
      Treatment with a single dose of Biltricide has proven to be effective. Prevention
      requires education of the population at risk and use of molluscacides. The
      control strategy must be adapted in function of the epidemiology of the disease,
      diagnostic data, cost and effectiveness of screening and treatment.

PMID- 9513159
TI  - [Intra-muscular artemether in the treatment of severe malaria: synthesis of
      current results].
AB  - Although still uncommon, resistance to quinine is being reported more and more
      often. Development of new drugs for treatment of severe malaria is necessary.
      Intramuscular artemether has been the focus of many comparative studies versus
      parenteral quinine with over 3,000 cases having been reported in Asia and Africa.
      For clearance of parasitemia current results document the greater efficacy of a
      five-day treatment using intramuscular artemether (2 x 80 mg on the first day and
      1 x 80 mg/day for the following four days in adults and 3.2 mg/kg on the first
      day and 1.6 mg/kg/day for the following four days in children) as compared to the
      standard seven-day treatment using intravenous quinine bichlorhydrate (20 mg/kg
      in 4 hours then 10 mg/kg every 8 hours). In terms of survival rate, coma recovery
      time, incidence of neurologic sequels, and fever clearance, the two drugs gave
      comparable results but artemether presents a slight advantage in some cases. No
      adverse effects particularly neurologic manifestations have been observed. From a
      practical standpoint administration of intramuscular artemether is easier than
      administration of intravenous quinine but the overall cost of treatment is about
      the same. Approved and available in most countries with endemic malaria,
      intramuscular artemether is included in the WHO List of Essential Drugs. The
      indication for use only in cases of severe malaria must be strictly respected to
      avoid development of resistance.

PMID- 9513161
TI  - [Evaluation of patient recruitment at the Yaounde Central Hospital].
AB  - A rehabilitation project at Yaounde Central Hospital (YCH) under way since 1990
      will soon reach completion with renovation of the maternity ward. In May 1996
      three surveys designed to assess recruitment were carried out in 660 patients
      admitted to the Outpatient Clinic (n = 241), Emergency Room (n = 183), and other
      departments (n = 236). The study questionnaire focused on familial, educational,
      and socio-economic background, home living conditions, reasons for admission, and
      treatment conditions. The findings of these studies indicated that the YCH is at
      the top-ranked treatment facility with recruitment covering the entire city and
      beyond. For people living in nearby areas the YCH is also the first care provider
      especially since income is low. Information campaigns for users, physicians, and
      health care workers are needed to reinforce confidence in the YCH. The YCH must
      do more to promote proper management, selection, and transport of patients from
      upstream facilities and continue its emphasis on wide access to health facilities
      for the population.

PMID- 9513162
TI  - [Trends in neonatal mortality analysed at ten year intervals at a pediatric
      service in Togo].

PMID- 9513160
TI  - [Preliminary survey of a school health program implementation in Guinea].
AB  - The Sectorial Adjustment Education Program implemented in Guinea by the Ministry
      of Pre-University Education in 1995 includes health-related measures. An
      important part is the fight against parasitosis and in particular against
      intestinal helminth infection which has been shown to impair cognitive function
      in school children. In order to obtain data for this purpose, a survey was
      carried out in 7 subprefectures across the country. A total of 1,649 children
      were examined to determine the prevalence in each school of macroscopic hematuria
      related schistosomiasis and of various intestinal helminthiasis in stools. In
      1468 of these children blood tests were also made to measure hemoglobin levels
      and detect malarial hematozoons. Overall prevalence rates were 60.0% for soil
      transmitted nematodes, 9.1% for urinary schistosomiasis, 57.6% for blood
      plasmodium, and 57.0% for anemia. Hemoglobin levels were lower in children
      presenting plasmodium, multiple parasitic infection, and high ankylostoma
      burdens. Prevalence rates varied widely between regions indicating differences in
      therapeutic measures. In two villages more than 200 children not attending school
      who had been informed by school children were treated. This word-of-mouth effect
      shows that school health programs are also useful to reach children outside the
      school health system.

PMID- 9513163
TI  - [Convulsions and mefloquine prophylaxis].

PMID- 9513164
TI  - [A case of hyperreactive malarial splenomegaly].

PMID- 9513165
TI  - [Prevalence of HIV infection in an internal medical service in Mozambique].

PMID- 9513166
TI  - [Indole non-production and antibiotic multiresistance of Vibrio cholerae 0:1 in
      Rwanda].

PMID- 9513167
TI  - [Home care by mothers of children under five for infantile diarrhea in a rural
      zone of Togo].

PMID- 9513168
TI  - [Obstetrical transport services and fetal-maternal mortality in Burkina Faso].

PMID- 9513169
TI  - [Addison's disease revealed by hypoglycemic convulsions].

PMID- 9513170
TI  - [Emerging pathologies].

PMID- 9513171
TI  - [Emerging and re-emerging zoonoses. Local and worldwide threats].
AB  - Emerging or re-emerging zoonoses is a relatively complex topic. The concept
      covers not only new or recently identified zoonotic agents but also agents that
      are already known but appear in regions and/or species in which they have not
      been previously observed and agents that disappear then reappear in a country in
      the form of an epidemic outbreak. Many wild or domestic species and almost all
      infectious agents may be involved. In general intervention either by vaccination
      or by elimination of suspect or contaminated individuals is easier in domestic
      animals than in wild animals especially since the latter may belong to an
      endanger species. Because of the wide range of pathogenic agents, animal vectors
      and target populations, there are a wide variety of epidemiological patterns and
      adapted surveillance and control strategies must be used with various degrees of
      success.

PMID- 9513173
TI  - [Host spectrum and virulence].
AB  - In an anthropozoonoses distribution of an infectious agent population into
      several host species at each generation can be considered to result in a
      fragmented anthropozoonoses environment. Insofar as reproductive success may vary
      between host species, gene flow becomes asymmetric and a source-sink
      anthropozoonoses system may be created. Under these conditions optimal virulence
      may be occur in any host species so that the source host species exerts the
      strongest selective pressure on the infectious agent. In the sink host species
      the virulence of the parasite may be sub- or super-optimal (stable
      misadaptation). This explains the gravity of parasitic infections that man shares
      with animals and the fact that virulence does not diminish with time.

PMID- 9513172
TI  - [Genetic predisposition to infectious diseases].
AB  - At the present time more is known about barriers to transmission of infectious
      agents between species than barriers to transmission within the same species.
      However differences in resistance to infection have been well-established within
      given species of various plants and domestic farm animals. Unsurprisingly several
      similar mechanisms have been observed in humans. A well-known human example of
      genetic protection is resistance to malaria in endemic areas which has been
      associated with polymorphism in alpha and beta chain globulin genes, cytoskeleton
      proteins, and protein/receptors on the surface of red blood cells. Studies
      regarding infection by Schistosoma mansoni show that the extent of infection
      depends largely on each individual's intrinsic resistance under the control of a
      single major gene which has now been located on q31-33 locus of the long arm of
      chromosome 5. This locus harbors several genes involved in differentiation of
      auxiliary T lymphocytes. With regard to HIV infection it has been known for
      several years that a small but significant number of individuals are relatively
      resistant. This resistance has been attributed to deletion of the gene coding for
      the chemokine receptor used by the virus as a co-receptor to infect macrophage.

PMID- 9513174
TI  - [The fate of parasites of animal origin transmitted to humans].
AB  - The fate of a parasite transmitted from an animal to man depends on the ability
      of the contaminating agent to reach a place where it can thrive, to find
      necessary nutrients, and to resist host defense mechanisms. The purpose of this
      study was to evaluate the incidence of transmission of parasites from animals to
      man and to determine to what extent transmission is followed by development.
      Stenoxenic parasites whose life cycle requires transmission from animals to man
      obviously develop in man and then return to animals. These parasites cause
      holozoonoses of the cyclozoonosis type. Some euryxenic parasites can develop as
      well in man as in animals. These parasites can cause holozoonoses of the
      amphixenoses type. Other presumably euryxenic parasites can be transmitted from
      animals to man but not vice versa. These parasites are hemizoonoses agents. Non
      transmission back from man to animals can be observed under several
      circumstances: incomplete development in man with failure to reach the stage at
      which transmission back to animals is possible; full development but with
      immaturity or sterility of the elements of dissemination necessary for
      transmission back to animals; full development but no way of evacuating elements
      of dissemination; full development and evacuation but with failure of elements of
      dissemination to survive. In these four cases man constitutes a dead-end for the
      parasite. A fifth possibility is that the parasite reaches full development but
      transmission back to animals cannot occur because man is not preyed upon by a
      carnivorous animal. In this case parasites are potential agents of holozoonoses
      and man is a cul-de-sac for the involved parasites.

PMID- 9513175
TI  - [Tropical animal and human rickettsial infections].
AB  - Advances in molecular biology have provided tools that have greatly clarified our
      knowledge of rickettsial diseases. Most rickettsias have been reclassified in the
      alpha subgroup of proteobacteria. Four groups of rickettsias have been
      identified: the spotted fever group, the typhus group, Ehrlichia, and Bartonella.
      Although still considered as a rickettsia, Coxiella burnetti, the agent causing Q
      fever, has been reclassified separately in the gamma subdivision of
      proteobacteria. Recognition of rickettsial disease is still based mainly on
      clinical manifestations (rash, eschar, and scratching sores). Little progress has
      been made in serologic testing. Indirect immunofluorescence is the most common
      technique. Diagnostic techniques based on molecular biology are currently
      available in only a small number of laboratories. Treatment with tetracyclines is
      indicated but prophylaxis through proper hygiene is the most effective approach.

PMID- 9513176
TI  - [Arbovirus infections. From virus, mosquitoes, animals and humans].
AB  - Arboviruses occur throughout the world in plants and animals: reptiles, birds and
      mammals including man. These relatively recent RNA-containing viruses have great
      evolutionary potential and are a major cause of epidemics. Arboviruses exhibit a
      dual life cycle involving continual transmission to and from the vertebrate host
      and arthropod vector which ingests or inoculates the agent during blood meals.
      Agents belong to many different viral families and represent an important source
      of emerging diseases. Because of the mode of transmission is vectorial, spread
      can enhanced by man-made changes in the ecosystem. This risk is often
      underestimated. The population explosion provides a great opportunity for the
      progression of these arboviruses.

PMID- 9513177
TI  - [International organization of the campaign against anthropozoonoses].
AB  - After briefly defining the scope of his presentation, the author will describe
      the respective roles of the different international, national and regional
      organization in the surveillance of anthropozoonoses. He will then restate the
      objectives of international control of anthropozoonoses, i.e. limit spread by
      strictly restricting exportations of animals and animal products (International
      Animal Health Code of the International Epizooties) and reduce disease incidence
      by coordinating the application of regional regulatory measures. The presentation
      will be fully illustrated by tables and examples from the field. In conclusion
      the author will emphasize the need for standardization of international control
      of anthropozoonoses to prevent possible spread as a result of greater free trade
      in the world.

PMID- 9513178
TI  - [Current status of animal rabies in France].
AB  - The main host reservoir and vector of rabies in Western Europe is the red fox
      (Vulpes vulpes). A vaccination strategy for this species has been developed and
      tested in Switzerland since 1978. Results indicate that the vaccine which is
      administered in spring and autumn for at least two consecutive years is more
      effective than destruction by shooting or gassing the animals. The same approach
      using bait containing increasingly effective and safe vaccines has been in use in
      France since 1986. By creating an immunological barrier from the English channel
      to the Swiss border, it has been possible to stop the southern progression of the
      disease. In the following years the vaccination program was extended to all
      contaminated areas in France (141,700 km2). From 1989 to 1996 rabies decreased in
      incidence by 99.7% and disappeared from 95% of the previously contaminated area.
      Although no case of rabies involving a non-flying mammal has been reported since
      October 1996, rabies cannot be considered as eradicated as long as places of
      active disease subsist in neighboring areas of Belgium and the Sarreland. Bat
      rabies in Europe is caused by two viral genotypes that have never been isolated
      in any species other than bats and man. A total of four cases of bat rabies have
      been diagnosed in France since 1989. All four cases occurred in the Serotine
      community including one in 1997. All cases of canine rabies reported in the last
      20 years have been observed in imported animals. The last was in 1995 and could
      have been prevented by stricter border control.

PMID- 9513179
TI  - [Current status of anthrax or black fever].
AB  - Although anthrax is one of the oldest recognized infectious diseases in the
      world, it remains widespread particularly in tropical zones such as Africa. The
      impact of this major zoonoses is further enhanced by the fact that the pulmonary
      form can be used for biological warfare. Recently there has been a revival of
      interest in anthrax and research has benefited greatly from advances in molecular
      biology. The main factors accounting for the virulence of Bacillus anthracis have
      been elucidated. The author reports current data concerning pathogenesis,
      epidemiology and diagnosis and reviews progress made in the field of prophylaxis
      especially with regard to vaccines.

PMID- 9513180
TI  - [Current status of Rift Valley fever. What lessons to deduce from the epidemics
      of 1977 and 1987?].
AB  - The epidemiology of Rift Valley Fever has undergone extensive revision over the
      last twenty years since the epidemics that occurred in Egypt in 1977 and
      Mauritania in 1987. From 1931 when the disease was first described until the end
      of the 70s, Rift Valley Fever was considered to be a relatively benign zoonoses
      for man that developed in domestic animals (especially sheep) periodically
      following heavy rainy seasons. The presumptive reservoir for the virus in latent
      years was an unidentified animal living in the wilderness. However the outbreaks
      in Egypt and Mauritania and data obtained from ensuing research led to complete
      reassessment of this assumption. Current data suggest that environmental factors
      (especially ecological changes caused by development of hydroelectric resources)
      and low-grade transmission in domestic animals (especially rodents) could account
      for survival of the virus in zones uninhabited by wild animals and in Sahelian
      areas.

PMID- 9513181
TI  - [Current status of trypanosomiasis].
AB  - Sleeping sickness is presently undergoing a recrudescence mainly as a result of
      major socioeconomic problems in Africa. Despite the reigning pessimism due to the
      currently unfavorable context (increasing incidence, lack of rapid diagnostic
      criteria, and unavailability of active non-toxic therapeutic agents), research
      data hold the promise of more effective control of this disease in the future.
      Mapping of infected households is now necessary to allow better early
      identification and follow-up of patients. Great advances have been made in the
      study of the pathogenesis of nervous involvement and it has been demonstrated
      that the characteristic symptoms of sleeping sickness are due to penetration of
      trypanosomes into the central nervous system (CNS) through the blood-brain
      barrier. However an unsolved problem is determining whether the blood-brain
      barrier has been broken and CNS involvement has occurred. This determination is
      important because neurologic involvement is a prerequisite for deciding when to
      undertake treatment using highly toxic melarsoprol. Research to identify new
      criteria for staging blood/lymph and nervous involvement is under way and
      encouraging results have been obtained using auto-antibodies against nervous
      system components. Although there is now greater hope that a vaccine will be
      developed in the future, treatment has not advanced greatly in the last 50 years.
      Pentamidine can be effective in some patients with "early-stage" nervous
      involvement. Melarsoprol is fatal in about 5% of patients treated. New drugs
      (e.g. nitroimidazoles) may become available one day but development is slow
      because most research is being done in a few university laboratories.

PMID- 9513182
TI  - [Current status of dengue].
AB  - Dengue has become a major public health problem in intertropical areas where an
      estimated 60 million new cases and 30,000 deaths occur annually. The causative
      agent is transmitted by the bite of Aedes mosquitoes which are the main and
      perhaps only reservoir of the disease. In addition to increasing incidence
      clinical manifestations of dengue have changed over the last 40 years. An
      increasing number of reported cases involve hemorrhage, shock, and other severe
      complications especially in Southeast Asia, northern regions of South America,
      and the Caribbean. Some of the same factors responsible for these changes are
      probably implicated in the development of other emerging viral diseases.

PMID- 9513183
TI  - The Department of Molecular Medicine at the University of Texas Institute of
      Biotechnology.

PMID- 9513184
TI  - Charcot-Marie-Tooth disease: lessons in genetic mechanisms.

PMID- 9513185
TI  - Comorbid migraine with aura, anxiety, and depression is associated with dopamine
      D2 receptor (DRD2) NcoI alleles.
AB  - BACKGROUND: Unrelated individuals (n = 242) were interviewed directly for the
      presence of migraine, anxiety disorders, and major depression. MATERIALS AND
      METHODS: The data described in this study are derived from a clinical genetic
      relational database that was developed initially for the genetic analysis of
      migraine. Genotyping of the DRD2 NcoI C to T polymorphism located in exon 6
      (His313His) was performed using previously described primers. RESULTS: A
      significantly increased incidence of migraine with aura (MWA), major depression,
      generalized anxiety disorder (GAD), panic attacks, and phobia was observed in
      individuals with the DRD2 NcoI C/C genotype compared with individuals with an
      DRD2 NcoI T allele. Specifically, 69% (91/131) of DRD2 NcoI C/C individuals in
      the present study met criteria for at least one of these neuropsychiatric
      disorders versus only 22% (4/18) of the DRD2 NcoI T/T individuals (Chi-square =
      15.29; p < 0.00005). The DRD2 NcoI C allele frequency is significantly higher
      (Chi-square = 17.13; p < 0.00002) in individuals with MWA, anxiety disorders,
      and/or major depression (C allele frequency = 0.80) than in individuals who have
      none of these disorders (C allele frequency = 0.67). CONCLUSIONS: These data
      indicate that MWA, anxiety disorders, and major depression can be components of a
      distinct clinical syndrome associated with allelic variations within the DRD2
      gene. Clinical recognition of this genetically based syndrome has significant
      diagnostic and therapeutic implications.

PMID- 9513186
TI  - Distinct roles of synapsin I and synapsin II during neuronal development.
AB  - The synapsins are a family of neuron-specific proteins, associated with the
      cytoplasmic surface of synaptic vesicles, which have been shown to regulate
      neurotransmitter release in mature synapses and to accelerate development of the
      nervous system. Using neuronal cultures from mice lacking synapsin I, synapsin
      II, or both synapsins I and II, we have now found that synapsin I and synapsin II
      play distinct roles in neuronal development. Deletion of synapsin II, but not
      synapsin I, greatly retarded axon formation. Conversely, deletion of synapsin I,
      but not synapsin II, greatly retarded synapse formation. Remarkably, the deletion
      of both synapsins led to partial restoration of the wild phenotype. The results
      suggest that the synapsins play separate but coordinated developmental roles.

PMID- 9513187
TI  - Expression of amphiphysin I, an autoantigen of paraneoplastic neurological
      syndromes, in breast cancer.
AB  - Amphiphysin I is a 128 kD protein highly concentrated in nerve terminals, where
      it has a putative role in endocytosis. It is a dominant autoantigen in patients
      with stiff-man syndrome associated with breast cancer, as well as in other
      paraneoplastic autoimmune neurological disorders. To elucidate the connection
      between amphiphysin I autoimmunity and cancer, we investigated its expression in
      breast cancer tissue. We report that amphiphysin I was expressed as two isoforms
      of 128 and 108 kD in the breast cancer of a patient with anti-amphiphysin I
      antibodies and paraneoplastic sensory neuronopathy. Amphiphysin I was also
      detectable at variable levels in several other human breast cancer tissues and
      cell lines and at low levels in normal mammary tissue and a variety of other non
      neuronal tissues. The predominant amphiphysin I isoform expressed outside the
      brain in humans is the 108 kD isoform which represents an alternatively spliced
      variant of neuronal amphiphysin I missing a 42 amino acid insert. Our study
      suggests a link between amphiphysin I expression in cancer and amphiphysin I
      autoimmunity. The enhanced expression of amphiphysin I in some forms of cancer
      supports the hypothesis that amphiphysin family members may play a role in the
      biology of cancer cells.

PMID- 9513188
TI  - Photodynamic tumor therapy: mitochondrial benzodiazepine receptors as a
      therapeutic target.
AB  - BACKGROUND: Photodynamic therapy employs photosensitive agents such as porphyrins
      to treat a variety of tumors accessible to light-emitting probes. This approach
      capitalizes on the selective retention of porphyrins by cancer cells. Cancer
      cells also have elevated levels of mitochondrial benzodiazepine receptors which
      bind porphyrins with high affinity. METHODS: Cultured cancer cell lines were
      exposed to porphyrin and porphyrin-like compounds and then irradiated with light.
      Cytotoxicity of this treatment was measured via clonogenic assays. Mitochondrial
      benzodiazepine receptor pharmacology was studied using [3H] PK11195 binding to
      cancer cell homogenates and isolated kidney mitochondrial membranes. RESULTS: We
      show that therapeutic potencies of porphyrins correlate closely with affinities
      for mitochondrial benzodiazepine receptors. Sensitivities of tumor cell lines to
      photodynamic therapy parallel their densities of these receptors. CONCLUSION: We
      propose that porphyrin photodynamic therapy is mediated by mitochondrial
      benzodiazepine receptors.

PMID- 9513191
TI  - [Pathophysiology and surgical treatment of hemifacial spasm].

PMID- 9513192
TI  - [Surgery of peripheral nerve: surgical management for thoracic outlet syndromes
      and carpal tunnel syndromes].

PMID- 9513193
TI  - [Surgical interruption of draining vein or dural sinus: treatment for
      petrotentorial dural arteriovenous malformation].
AB  - The authors report three cases with petrotentorial dural arteriovenous
      malformation who underwent surgical interruption of the draining vein or dural
      sinus. They discuss the rationale and feasibility of this surgical procedure.
      Case 1 (70-year-old man) presented with trigeminal neuralgia and cerebellar
      ataxia caused by subarachnoid and cerebellar hemorrhage. Case 2 (68-year-old man)
      with trigeminal neuralgia due to venous mass effect. Case 3 (48-year-old man)
      with dementia caused by venous ischemia in the bilateral thalami. Cases 1 and 2
      underwent lateral suboccipital craniotomy followed by infratentorial
      supracerebellar approach, and the draining vein was interrupted by aneurysmal
      clip under the cerebellar tentorium. Case 3 underwent surgical occlusion of the
      straight sinus by occipital transfalcine transtentorial approach after
      transarterial embolization had failed. Intraoperative digital subtraction
      angiography revealed the disappearance of dural AVMs in all three cases. The
      clinical symptoms disappeared postoperatively, and follow-up 6-vessel-angiography
      2, 20, 11 months later, respectively, revealed no recurrence of dural AVMs. It
      has recently been proposed that many cranial dural AVMs with leptomeningeal
      venous drainage require only interruption of the draining vein as it enters the
      subarachnoid space for successful, lasting elimination. The striking clinical and
      radiological improvement in these cases emphasizes the pivotal role of surgical
      occlusion of the draining vein for petrotentorial dural AVMs which are not
      amenable to cure by endovascular procedures.

PMID- 9513194
TI  - [Delayed ischemic neurological deficit that developed over 15 days after
      subarachnoid hemorrhage].
AB  - We retrospectively studied subarachnoid hemorrhage (SAH) patients with delayed
      ischemic neurological deficit (DIND), and analyzed the factors causing extremely
      late onset of deficits occurring over 15 days after onset of the SAH. Among 605
      patients with SAH, 201 (33%) developed DIND. Among DIND patients, 137 had
      undergone early aneurysm surgery. In these 137 patients, onset date of DIND was
      definite in 131 patients. Six patients (5%) developed DIND over 15 days after
      SAH. All 6 had asymptomatic angiographical vasospasm and infections, most often
      meningitis, before the onset of DIND. Compared with cases in which there was
      ordinary onset of DIND, other statistically significant factors among these 6
      patients were intracerebral hemorrhage, sepsis and meningitis. We suspect that
      DIND were manifested subclinically in the early period because of the associated
      hyperdynamic hemodynamics resulting from sepsis in these patients.

PMID- 9513189
TI  - Receptors for advanced glycosylation endproducts in human brain: role in brain
      homeostasis.
AB  - BACKGROUND: Advanced glycation end products (AGEs) are the reactive derivatives
      of nonenzymatic glucose-macromolecule condensation products. Aging human tissues
      accumulate AGEs in an age-dependent manner and contribute to age-related
      functional changes in vital organs. We have shown previously that AGE scavenger
      receptors are present on monocyte/macrophages, lymphocytes, and other cells.
      However, it remains unclear whether the human brain can efficiently eliminate AGE
      modified proteins and whether excessive AGEs can contribute to inflammatory
      changes leading to brain injury in aging. MATERIALS AND METHODS: To explore the
      expression and characteristics of AGE-binding proteins on CNS glia components and
      their putative function, such as degradation of AGE-modified proteins, primary
      human astrocytes and human monocytes (as a microglial cell surrogate) and murine
      microglia (N9) cells and cell membrane extracts were used. Immunohistochemistry
      was used to examine the distribution of AGE-binding proteins in the human
      hippocampus; RT-PCR techniques were used to examine the biologic effects of AGEs
      and a model AGE compound, FFI, on AGE-binding protein modulation and cytokine
      responses of human astrocytes and monocytes. RESULTS: Our results showed that AGE
      binding proteins AGE-R1, -R2, and -R3 are present in glial cells. Western blot
      analyses and radiolabeled ligand binding studies show that AGE-R1 and -R3 from
      human astrocytes bind AGE-modified proteins; binding could be blocked by anti-AGE
      R1 and anti-AGE-R3 antibodies, respectively. Immunohistochemistry showed that AGE
      R1 and -R2 are expressed mainly in neurons; only some glial cells express these
      AGE-binding proteins. In contrast, AGE-R3 was found only on those astrocytes
      whose positively stained foot processes extend and surround the sheath of
      microcapillaries. RT-PCR results showed that mRNAs of the three AGE-binding
      proteins are expressed constitutively in human astrocytes and monocytes, and
      receptor transcripts are not regulated by exogenous AGEs, the model AGE compound
      FFI, or phorbol ester. At the concentrations used, GM-CSF appears to be the only
      cytokine whose transcript and protein levels are regulated in human astrocytes by
      exogenous AGEs. CONCLUSIONS: The selective presence of AGE-binding proteins in
      pyramidal neurons and glial cells and their roles in degrading AGE-modified
      protein in glial cells suggest that the human brain has a mechanism(s) to clear
      AGE-modified proteins. Without this capacity, accumulation of AGEs
      extracellularly could stimulate glial cells to produce the major inflammatory
      cytokine GM-CSF, which has been shown to be capable of up-regulating AGE-R3. It
      remains to be determined whether AGE-binding proteins could be aberrant or down
      regulated under certain pathological conditions, resulting in an insidious
      inflammatory state of the CNS in some aging humans.

PMID- 9513195
TI  - [Efficacy of the fluid attenuated inversion recovery (FLAIR) sequence of MRI as a
      preoperative diagnosis of hippocampal sclerosis].
AB  - A newly advanced MRI pulse sequence, the FLAIR (fluid attenuated inversion
      recovery) imaging, in which a long TE spin echo sequence is used with suppression
      of the CSF with an inversion pulse, displays the CSF space as a no-signal
      intensity area. There have been only a few reports on the FLAIR pulse sequence of
      temporal lobe epilepsy (TLE) as yet. We examined 9 cases of intractable TLE by
      FLAIR images and analyzed the advantages and disadvantages of the FLAIR pulse
      sequence for decision making on temporal lobectomy. All patients underwent
      anterior temporal lobectomy with hippocampectomy, and the diagnoses were
      confirmed histologically after surgery. Abnormally high T2 signals (HT2S) were
      more conspicuous with the FLAIR sequence than with any of the conventional
      sequences. Tilted axial plane, orientated along to the long axis of the
      hippocampal body, clearly demonstrated hippocampal atrophy (HA). Selection of a
      FLAIR sequence into the routine MR examination of patients with TLE is
      recommended.

PMID- 9513196
TI  - [Two cases of subarachnoid hemorrhage associated with neurofibromatosis type I: a
      case of multiple cerebral aneurysms and arteriovenous malformation, and another
      case of an anterior communicating artery aneurysm].
AB  - Two cases of subarachnoid hemorrhage associated with neurofibromatosis type I
      (von Recklinghausen's disease) are reported. A 30-year-old male patient (case 1)
      had been diagnosed as having neurofibromatosis type I due to neurofibroma and
      cafe-au-lait spot. He suffered from subarachnoid hemorrhage and angiography
      showed multiple aneurysms in the right and left middle cerebral arteries and left
      internal carotid artery. He also had arteriovenous malformation in the left
      temporal lobe. Case 2 was that of a 62-year-old female patient with neurofibroma
      and cafe-au-lait spot. She suffered from subarachnoid hemorrhage and angiography
      showed an aneurysm in the anterior communicating artery. Both patients were
      discharged with no deficits after neck clipping, however they both suffered from
      large-sized hematoma in the punctured site of the femoral artery after
      angiography. The cerebral aneurysms associated with neurofibromatosis type I are
      often multiple and may coexist with arteriovenous malformation.

PMID- 9513197
TI  - [Ruptured aneurysm of the marginal branch of the superior cerebellar artery: case
      report].
AB  - The authors report a rare case of a ruptured aneurysm arising from the marginal
      branch of the left superior cerebellar artery. At the first retrosigmoid
      craniectomy carried out on the day of hospitalization, the clip was wrongly
      placed on the anterior inferior cerebellar artery (AICA). The unanticipated
      accident was due to incomplete dissection of a thick and severely adhered
      subarachnoid clot and the mistake was made because the course of the marginal
      artery was similar to that of the AICA. At the second operation undergone 1 week
      later, the aneurysm was easily and successfully clipped. After
      ventriculoperitoneal shunting, the patient returned to normal except for left
      hearing loss. The authors suppose that delayed surgery would be beneficial as a
      rule for ruptured aneurysms of the peripheral branch of the cerebellar arteries
      not only because dissection is easier but also because the risk of rebleeding and
      vasospasm are reported to be low in such aneurysms.

PMID- 9513198
TI  - [A case of peripheral, fusiform type aneurysm originating from the superior
      cerebellar artery].
AB  - We reported a case of a 33-year-old woman who presented a subarachnoid hemorrhage
      due to rupture of an aneurysm arising from the ambient segment of the superior
      cerebellar artery (SCA). The patient who complained of severe headache and nausea
      was admitted on April 6, 1996. A CT scan revealed subarachnoid hemorrhage in the
      left cerebellopontine cistern. Left vertebral angiography showed a fusiform type
      aneurysm of the ambient segment of the left SCA. Trapping of the aneurysm was
      successfully performed via the subtemporal approach on the day of admission,
      April 6, 1996. She was discharged with no deficits on May 2, 1996. Fusiform type
      aneurysm arising from SCA is very rare. Only 3 cases have been reported in the
      literature. We discussed the pathogenesis of this aneurysm and the timing of
      surgery.

PMID- 9513199
TI  - [Usefulness of neuroendoscopy and a neuronavigator for removal of clival
      chordoma].
AB  - We report a case of large clival chordoma. The patient was a 56-year-old male who
      was admitted to our hospital with left eye ptosis and diplopia of 2 months
      duration. On admission, neurological examinations revealed oculomotor nerve palsy
      of the left eye. Skull radiographs with polytomographs demonstrated marked
      destruction of the clivus. A plain computed tomography (CT) scan revealed a large
      iso-attenuated mass in the clivus, extending anteriorly into the sphenoidal
      sinus, superiorly into the suprasellar cistern, bilaterally into the petrous
      apex, posteriorly into the prepontine cistern and caudally into the foramen
      magnum. An enhanced CT scan demonstrated a slightly enhanced tumor. A high
      resolution bone-window CT scan revealed marked destruction of the clivus and
      bilateral petrous apex. Magnetic resonance imaging (MRI) scans disclosed a large
      enhanced mass extending superiorly into the suprasellar cistern, bilaterally into
      the petrous apex and inferiorly into the foramen magnum. The tumor extended so
      widely that we decided on a one-stage operation via a transsphenoidal sublabial
      transseptal approach and transoral transpalatal approach. At surgery, we employed
      a neuronavigator and Codman 4-mm rigid neuroendoscope with 0 degree, 30 degrees
      and 70 degrees angled lenses. The tumor was very soft and suckable, and could be
      easily removed by applying CUSA, a pituitary curette and suction. The
      neuronavigator was particularly useful because the surgeon had a real-time two
      dimensional representation of the position of the tip of this device in the
      corresponding imaging space intraoperatively. The neuroendoscope also proved
      useful, since remnant tumor tissues that could not be seen under an operating
      microscope were frequently recognized near or around the entrance of the tumor
      cavity, cavernous sinus region and petroclival junction area. The surgeon was
      able to remove these remnants safely by checking on the neuroendoscope monitor.
      The tumor was excised completely. The dead space of the tumor cavity was
      reconstructed using a free rectus abdominis muscle flap. Postoperatively,
      cerebrospinal fluid leakage and meningitis were recognized, but improved
      following spinal drainage for one week and intrathecal injection of antibiotic.
      The oculomotor nerve palsy of the left eye also showed good recovery at one month
      after the operation. Recently, skull base surgery has undergone considerable
      developments. Neuroendoscopes and neuronavigators are very helpful for the
      neurosurgeon in performing skull base tumor surgery safely and with precision,
      although further instrument modifications are needed.

PMID- 9513200
TI  - [Traumatic intracerebral pneumocephalus communicating with two different
      paranasal sinuses: a case report].
AB  - We report a case of a 17-year-old male who had hit the front of his head in a
      traffic accident. CT scan revealed contusional hemorrhage and pneumocephalus of
      the left frontal lobe 10 hours after the accident. A month later he complained of
      rhinorrhea and CT scan revealed intracerebral pneumocephalus. One day he
      complained of headache and began to vomit after he sneezed. CT scan revealed that
      the pneumocephalus had become worse and air had spread throughout the
      subarachnoid space. Bone CT scan revealed the air communicated from the frontal
      sinus to the intracerebral air cavity. 3D-CT scan revealed bone defect in the
      roof of the ethmoid sinus. The intraoperative findings revealed that the
      intracerebral air cavity communicated with the frontal sinus and ethmoid sinus.
      Though the brain which dropped into the paranasal sinus, adhered to the dura
      mater around the bone defect, a part of the brain had come off from the dura
      mater around the frontal sinus. We suspected that the intracerebral air cavity
      communicated with the frontal sinus initially. When the air cavity communicated
      with the ethmoid sinus secondarily, intracranial pressure abated and air came
      into the subarachnoid space from the frontal sinus.

PMID- 9513201
TI  - [Cerebral vascular malformations: a review].

PMID- 9513202
TI  - [Stress proteins: recent research progress].

PMID- 9513203
TI  - [Immunohistochemical appearance of complement protein, C4d, in the nervous system
      and its significance].

PMID- 9513204
TI  - [Clinical effects of sodium ozagrel and urokinase in patients with acute cerebral
      infarction in the territory of the internal carotid artery].
AB  - In this study, the clinical effects were compared between a thromboxane
      synthetase inhibitor (sodium ozagrel) and a thrombolytic agent (urokinase) in
      patients with acute cerebral infarction. The subjects consisted of 598 patients
      admitted on the day of the onset of the cerebral infarction in the territory of
      the internal carotid artery who showed a low density area on CT images within 5
      days. Of these patients, 300 were treated with sodium ozagrel and classified as
      Group Oz, while the remaining 298 were treated with urokinase and classified as
      Group Ur. The results were as follows: 1. In group Oz, complete recovery of motor
      impairment was seen in 209 (69.7%) patients. Complete recovery within 3 weeks
      after onset was seen in 186 (62.0%) patients. In group Ur, complete recovery of
      motor impairment was seen in 175 (58.7%) patients. Complete recovery within 3
      weeks after onset was seen in 120 (40.3%) patients. Therefore, a higher incidence
      of complete recovery of the motor impairment was noted in group Oz [p < 0.001:
      chi 2 test]. Similarly, complete recovery within 3 weeks after onset was more
      frequent in group Oz [p < 0.001: chi 2 test]. 2. In group Oz, complete recovery
      was made contribution statistically by Anosognosia (Ag) and unilateral neglect
      (UN) on admission [multivariate analysis: p < 0.01]. In group Ur, complete
      recovery was made contribution statistically by Ag (p < 0.01), UN (p < 0.01) and
      aphasia (p < 0.05). 3. Progressive stroke was observed in 29 (9.5%) patients in
      the group Oz and in 71 (23.0%) patients in group Ur. There was a higher incidence
      of progressive stroke in group Ur [p < 0.001: chi 2 test] 4. All patients with
      progressive stroke had initial evidence of deterioration of neurological deficits
      within 6 days after the onset in group Oz, and within 5 days after the onset in
      group Ur. The maximal period from the beginning to the end of the deterioration
      of neurological deficit was 7 days. 5. In group Oz, progressive stroke was only
      seen in 29 (29.9%) of the patients who were admitted with motor disturbances and
      unilateral neglect. In group Ur, progressive stroke was seen in 8 (4.3%) of the
      187 patients with motor disturbances without higher cortical dysfunction, in 17
      (47.2%) of the 36 patients with motor disturbances and higher cortical
      dysfunction without unilateral neglect and was seen in 46 (61.3%) of the patients
      with motor disturbances and unilateral neglect. 6. Hemorrhagic infarction was
      observed in 14 (4.6%) patients in group Oz and in 31 (10.0%) patients in group
      Ur. There was a higher incidence of hemorrhagic infarction in group Ur [p <
      0.001: chi 2 test]. 7. In group Oz, there was a higher incidence of hemorrhagic
      infarction among patients with atrial fibrillation (Af) on the ECG [p < 0.001:
      chi 2 test]. Similarly, in group Ur, hemorrhagic infarction was more frequent
      among patients with atrial fibrillation (Af) on the ECG [p < 0.001: chi 2 test].
      Therefore, sodium ozagrel was clinically more efficient and safer than urokinase
      in patients with acute cerebral infarction.

PMID- 9513205
TI  - [Effects of L-threo-Dops on orthostatic hypotension in Parkinson's disease].
AB  - Effects of L-threo-Dops (Dops) administration on orthostatic hypotention were
      evaluated with changes in blood pressure by postural change (lying to standing
      position) and subjective symptoms in 15 patients of Parkinson's disease having
      symptoms of orthostatic hypotention. Orthostatic syncope had improved
      significantly (p < 0.01) after 2 and 4 weeks of administration with maintenance
      dose of 460 mg/day of Dops in average. In the standing-up (Schellong) test,
      decrease in blood pressure levels by a postural change, both with systolic and
      diastolic blood pressure, was significantly smaller at 3, 5 and 10 minutes after
      standing after 4 weeks of drug administration. Decrease in the blood pressure
      level immediately after standing-up improved by 10.2 +/- 4.0 for systolic and 6.5
      +/- 1.8 for diastolic (mmHg, mean +/- SE) (p < 0.01). The group that showed
      improvement in orthostatic syncope had a significant improvement in decline in
      blood pressure by standing after administration of Dops, while the group without
      any change in severity of syncope did not show significant improvement in
      orthostatic hypotention.

PMID- 9513206
TI  - [Clinical and neuroradiological evaluation of the long-term surviving siblings of
      Sanfilippo syndrome A type].
AB  - The siblings of Sanfilippo syndrome type A (MPS III A) have been reported. The
      relationship of their parents was the first cousins. Case 1: A 30-year-old
      Japanese man was hospitalized because of gait disturbance and mental impairment.
      His early somatic and mental development was normal until 9 years of age when
      mental deterioration had developed. Speech and gait disturbances and double
      incontinence occurred at 18 years of age. He could not walk at 21 years of age.
      Those symptoms were slowly progressive. Case 2: A 32-year-old Japanese man, the
      elder brother of case 1, had a similar clinical history to that of case 1. Their
      neurological findings revealed mental impairment, coarse face, positive forced
      grasp and sucking reflexes, and pyramidal signs. Lumbar X-ray showed
      platyspondylitis, compression fracture of L 1 and osteoporotic changes. Brain MRI
      of both cases showed brain atrophy, ventricular dilatation and abnormal high
      intensity signals near the posterior horn of the lateral ventricles on T2
      weighted image. Low perfusion images of fronto-parietal regions were seen in the
      early phase of SPECT using 123I-IMP. This siblings were diagnosed as Sanfilippo
      syndrome type A because of heparan sulfaturia and deficiency of heparan sulfate
      sulfamidase of the lymphocytes. Average life span of Sanfilippo syndrome type A
      is not so long but the age of our cases is over 30 years of age.

PMID- 9513207
TI  - [Occlusion of anterior and middle cerebral arteries after closed head injury: a
      case report].
AB  - We report a case of traumatic anterior and middle cerebral arteries occlusion. A
      23-year-old man was admitted to our hospital following an automobile accident. He
      was comatose and had a small skin laceration on the left temporal region. The
      pupils did not react to light. CT scan revealed traumatic subarachnoid hemorrhage
      at the basal cistern and left sylvian fissure. His consciousness gradually
      recovered, but he became aphasic 4 days after the trauma. Cerebral angiography
      showed a irregularity of the left internal carotid artery at C1 portion and
      occlusion of left anterior and middle cerebral artery at A1 and M1 portion. CT
      scan showed low density area in the left middle cerebral artery distribution.
      Five months later, follow-up angiography disclosed recanalization of anterior and
      middle cerebral arteries. In our case, thrombus formation at C1 portion of left
      internal carotid artery might have occurred to result in the embolic occlusion of
      the anterior and middle cerebral arteries. To date, 34 cases of traumatic middle
      cerebral artery occlusion have been reported. However there have been only 2
      cases which accompanied anterior cerebral artery occlusion.

PMID- 9513208
TI  - [Autoantibody to glutamate decarboxylase in a patient with spinocerebellar
      degeneration and Sjogren syndrome].
AB  - We report a 52-year-old woman with Sjogren syndrome from the age of 46, developed
      cerebellar ataxia, autonomic dysfunction and dysarthria at 50. She had no family
      history, and all known causes of cerebellar disease were excluded. Serum of the
      patient contained autoantibodies directed against glutamic acid decarboxylase
      (GAD) which was an enzyme involved in the biosynthesis of GABA. She also had
      autoantibodies that were specific with Sjogren syndrome (SS-A, anti-nuclear
      antibody). Anti-GAD antibody changed into negative after high dose intravenous
      and oral corticosteroid therapy, but symptoms did not improve. Western blot
      method revealed abnormal bands to human neuroblastoma cell line (10, 43, 49 kDa),
      considered relatively specific to nervous tissue. In this case cerebellar ataxia
      and atrophy were caused by autoimmune pathogenesis including cerebellar GABAergic
      system and central nerve cells.

PMID- 9513209
TI  - [Acute transverse myelitis presenting with syrinx formation associated with anti
      sulfated glucuronyl lactosaminyl paragloboside antibody and anticardiolipin
      antibody].
AB  - A 37-year-old woman was admitted because of rapidly progressive unsteady gait,
      back pain and ascending dysesthesia below the lower chest level. On admission,
      she showed ataxic gait, positive Romberg's sign, severely impaired deep sensation
      of lower extremities, and vesico-rectal disturbance. Deep tendon reflexes in both
      lower extremities were brisk, while normal in the upper extremities. Babinski's
      sign was positive on both sides. On laboratory data, antinuclear antibody, immune
      complex and the low titer of IgG anticardiolipin antibody as well as IgM anti
      sulfated glucuronyl lactosaminyl paragloboside (SGLPG) antibody were positive in
      her serum. Cerebrospinal fluid showed pleocytosis and increased protein level,
      but no oligoclonal IgG bands. The posterior tibial nerve SEP showed no P39 peak
      with normal latency of N20. Spinal MRI revealed mild cord swelling and syrinx
      formation at T7 to T9 level. Steroid therapy including pulse therapy with
      methylprednisolone was effective. The present case was diagnosed as acute
      transverse myelitis (ATM) similar to lupoid sclerosis, and to the best of
      knowledge, the first case of ATM with anti-SGLPG antibody. It is speculated that
      the autoimmune mechanism with anti-SGLPG antibody and anticardiolipin antibody by
      reacting with the endothelial cells in the central nervous system might
      contribute to causing ATM in our case.

PMID- 9513210
TI  - [The autopsy case of traumatic carotid artery dissection].
AB  - The results of an autopsy of a 78-year-old female patient with an occluded of the
      right internal carotid artery after a traffic accident are reported. She
      presented with consciousness disturbance, right conjugate deviation, left
      hemiparesis and left pathological reflex. Evidence of right skull and clavicular
      fractures seemed to suggest that severe hyperextension of her neck associated
      with contralateral lateral flexion had stretched her carotid artery. Although she
      was treated with antiplatelet therapy, her cerebral swelling due to right global
      infarction progressed and she died due to bilateral cerebral herniation three
      days after injury. The autopsy disclosed right dissecting carotid artery
      occlusion and subadventitial dissection was revealed histologically. When a
      hematoma dissect the media and adventitia of the carotid artery wall, the outer
      wall weakens and may dilate without narrowing the lumen of the carotid artery. In
      this case, the vessel occlusion was considered to be due to a primary intramural
      hematoma which developed and subsequently ruptured through the intima into the
      vessel lumen. Early diagnosis and treatment are necessary for improving the
      prognosis of this disease entity. A patient with poor colateral flow, such as in
      this case, will show a rapid progression of cerebral infarction. It is best to
      consider surgical treatment in this case if the other traumatic lesions are able
      to tolerate surgery.

PMID- 9513211
TI  - [A case of chronic enteroviral meningitis and hydrocephalus associated with
      Bruton type agammaglobulinemia].
AB  - We report a 10-year-old boy with chronic enteroviral meningitis associated with
      agammaglobulinemia (CEMA) and hydrocephalus. He was treated with a low-dose
      intravenous administration (100 mg/kg/4 weeks) of gammaglobulin (gamma-gl) since
      he was diagnosed as having Bruton type agammaglobulinemia at 1 year of age. At
      this admission, neurological examination revealed meningeal signs, Babinski sign,
      frontal signs, urinary incontinence, and mental retardation (IQ = 48) which was
      considered to be a sequela of the enteroviral encephalitis which had occurred in
      his first year of life. T 1-weighted MR imaging of the brain following gadolinium
      administration revealed a marked dilatation of the lateral ventricles and dense
      enhancement of the meninges. Enterovirus was detected in the cerebrospinal fluid
      (CSF) using tissue culture. Histological examination of a biopsied leptomeningeal
      specimen revealed inflammatory thickening, which was a likely cause of the
      obstruction to the flow of CSF. The hydrocephalus in this patient was treated
      with external drainage of CSF from the lateral ventricle. The CEMA was brought
      into remission by means of the intraventricular administration of gamma-gl, at a
      dose of 125-250 mg/week (total dose: 1.5 g/8 weeks), in addition to the high dose
      intravenous administration (400 mg/kg/4 weeks) of gamma-gl. Because of the poor
      prognosis of patients with CEMA, the intraventricular administration of gamma-gl
      should be initiated immediately following a diagnosis of enteroviral meningitis.

PMID- 9513212
TI  - [Acute hypertensive encephalopathy].

PMID- 9513213
TI  - [A case of Brown-Sequard syndrome caused by demyelinating disease].

PMID- 9513214
TI  - "Clinical reasoning" classification.

PMID- 9513215
TI  - Nipple discharge.

PMID- 9513216
TI  - Preventing diabetic nephropathy: the role of primary care.
AB  - Diabetic nephropathy is the leading cause of end-stage renal disease in the
      United States and is associated with significant human and economic cost. It is
      recognized that care of the person with diabetes should be focused on the
      prevention of the many devastating long-term complications of the disease. The
      primary care provider is in a key position to implement good preventive care.
      Monitoring for microalbuminuria is the accepted method for identifying early
      nephropathy. Individual providers need to be aware of current guidelines for
      performing screening exams. Once early nephropathy is detected, prudent care with
      tight glycemic control, angiotension-converting enzyme therapy, control of
      hypertension, and lifestyle risk-factor modification are warranted. Currently,
      there is strong indication that the progression of renal disease can be slowed
      with appropriate early interventions. Positive outcomes are dependent on timely
      detection of microalbuminuria.

PMID- 9513217
TI  - Kawasaki disease: a dangerous acute childhood illness.
AB  - Kawasaki disease is an acute febrile illness most commonly seen in children under
      the age of 5. It is characterized by fever, rash, cervical lymphadenopathy,
      bilateral nonexudative conjunctivitis, oropharyngeal mucosal changes, and
      erythema of the hands and feet followed by desquamation. However, a child with
      Kawasaki disease may not exhibit all of these symptoms. The disease resembles
      many other childhood illnesses, such as measles and scarlet fever, and
      misdiagnosis is common. Left untreated, Kawasaki disease has potential life
      threatening consequences; 20% to 25% of children develop coronary artery
      aneurysms as a result. Although no specific laboratory tests exist that identify
      Kawasaki disease definitively, there are clinical and laboratory findings that
      guide diagnosis and treatment. Treatment includes the hospitalization of the
      child and subsequent administration of high doses of aspirin and intravenous
      immunoglobulin. With recovery, aspirin doses are reduced and the child may be
      monitored at home with outpatient follow-up. It is imperative that the health
      care provider be aware of the symptoms of Kawasaki disease in order to make the
      diagnosis and treat the child before cardiac sequelae ensue.

PMID- 9513218
TI  - Hyperthyroidism: an unusual case presentation.
AB  - Hyperthyroidism is the most common disorder of the thyroid. Patients typically
      present with complaints consistent with a hypermetabolic state, including
      nervousness, weight loss, heat intolerance, palpitations, irritability, and
      tremor. This case report reviews a 34-year-old woman who presented with
      unilateral upper extremity weakness, weight gain, and an episode of atrial
      fibrillation, the latter coinciding with a 36-hour lack of sleep and excess
      alcohol and caffeine intake. Although an extensive neurologic evaluation failed
      to identify any abnormality, the patient's laboratory analysis revealed
      elevations in thyroxine (T4) and triiodothyronine (T3) levels with unsuppressed
      thyroid-stimulating hormone levels. Subsequent treatment with the antithyroid
      drug methimazole (Tapazole) provided complete relief of symptoms. This case
      report illustrates how health care providers can be diverted to pursue a
      neurologic etiology when muscle weakness presents as a unilateral symptom.
      Plausible alternative causes for muscle weakness and other symptoms are
      presented.

PMID- 9513219
TI  - Using unannounced standardized patients to assess the HIV preventive practices of
      family nurse practitioners and family physicians.
AB  - Measuring health risk assessment and counseling recommendations can be
      challenging. In this study, unannounced standardized patients (lay individuals
      trained to replicate a clinical encounter consistently) were used to evaluate HIV
      preventive performance of 22 family nurse practitioners (NPs) and family
      physicians. Standardized patients were trained to present an identical scenario
      of a heterosexual individual at risk for HIV exposure. Audiotaping via a hidden
      microphone and recorder was used to validate the reproducibility of clinical
      encounters and accuracy of standardized patient assessment. Standardized patients
      were highly accurate in both case portrayal and assessment activities with an
      indexed Kappa coefficient of 0.82. Determining risk, including condom use, sexual
      orientation, and number of past sexual partners, was performed less often than
      experts advise by both physicians and NPs (done between 9% and 63% of
      encounters). Providing patient education to reduce risk, including educating
      about abstinence, mutual monogamy, and limiting sexual partners, was also done in
      only 9% to 36% of encounters. The methodology used was innovative. There is room
      for improvement in the provider participants' clinical performance of HIV risk
      assessment, patient education, and counseling. However, the results of this case
      study cannot be generalized.

PMID- 9513220
TI  - The quality renaissance.

PMID- 9513221
TI  - Drug interactions and protease inhibitor therapy in the treatment of HIV/AIDS.

PMID- 9513222
TI  - Trigger point relief.

PMID- 9513223
TI  - Procedural sedation.

PMID- 9513224
TI  - Delirium and depression in the elderly.

PMID- 9513225
TI  - Academic nursing: a desirable career?

PMID- 9513227
TI  - A critical analysis of physician research into nursing practice.

PMID- 9513226
TI  - Nursing's role in pain management across the health care continuum.

PMID- 9513228
TI  - OPT: transformation of nursing process for contemporary practice.
AB  - Over time, clinical, educational, and social forces have influenced the
      development of three generations of traditional nursing process. The first
      generation was concerned with problems and process. Analysis of second-generation
      models revealed interest in understanding the nature of diagnosis and diagnostic
      reasoning. We have proposed a third generation model that underscores the
      importance of critical, metacognitive, and thinking skills that support outcome
      specification and testing in clinical reasoning. Clinicians, educators, managers,
      and administrators are invited to consider the OPT model as an alternative to
      traditional nursing process. The OPT model may be one of many transitional
      reasoning models needed for contemporary nursing practice.

PMID- 9513229
TI  - Twenty-first century learning.

PMID- 9513230
TI  - Medicare reimbursement for advanced practice nurses: in the front door!

PMID- 9513231
TI  - Overdrugging and undertreatment in primary health care.

PMID- 9513233
TI  - News from NINR.

PMID- 9513232
TI  - The preferable future of nursing.

PMID- 9513234
TI  - Liability issues of interest to the oculoplastics specialist.

PMID- 9513235
TI  - RAND study: workforce requirements and provider supply relevant to oculoplastic
      and orbital surgery.
AB  - The 1995 RAND study Estimating Eye Care and Workforce Requirements analyzes the
      United States' supply, demand, and need for eyecare providers. Portions of the
      RAND study were prepared along traditional ophthalmic specialty lines. This
      article extracts and further analyzes those portions of the study that are of
      interest to active subspecialty oculoplastic surgeons. The RAND study results
      indicate a significant current and very probable future oversupply of
      oculoplastics workforce personnel. This oversupply is further exacerbated when a
      RAND study underestimate of the number of new fellowship-trained oculoplastic
      surgeons is corrected.

PMID- 9513236
TI  - Histopathologic changes of the eyelid skin following trichloroacetic acid
      chemical peel.
AB  - The use of trichloroacetic acid (TCA) as a periorbital and eyelid peel for skin
      rejuvenation is gaining significant acceptance among oculoplastic surgeons,
      dermatologists, and other surgery groups. In spite of the current enthusiasm,
      there remain potentially serious complications resulting from any periorbital
      peel. Cases of cicatricial ectropion have been reported in phenol-peeled
      patients, and lower eyelid ectropion has reportedly occurred in patients
      undergoing deep eyelid peel in conjunction with a blepharoplasty (1,2). To avoid
      this complication, it is necessary to better understand the depth of the wound
      produced by different strengths and combinations of peeling agents applied to
      living eyelid tissue and, more important, to determine the concentrations of TCA
      that are likely to lead to cicatricial ectropion when applied in a consistent
      fashion. We chose upper-eyelid skin because it is easier to obtain for
      histopathologic study than lower-eyelid skin and, in our experience, is more
      sensitive to hypertrophic changes after chemical peeling or carbon dioxide laser
      resurfacing. We applied TCA to the preseptal skin of 10 patients 48 h before
      standard upper-eyelid blepharoplasty. The acid was applied to produce a "frost,"
      using varying concentrations of acid, ranging from 20 to 50%. The treated skin
      removed at the time of blepharoplasty was reviewed in a masked fashion by a
      dermatopathologist to determine the depth of necrosis. We found that superficial
      peels with necrosis involving 30% of the epidermis were produced by the lowest
      concentration combination of TCA applied (20% followed by 0%). As the strength
      increased, so did the depth of peel. The combination of 50% followed by a second
      application of 50% produced the deepest peel, with necrosis into the papillary
      dermis. This finding would indicate that the chance of developing cicatricial
      ectropion with any of the tested combinations of TCA should be very remote.

PMID- 9513237
TI  - Age-related changes in type-I collagen synthesis in human eyelid skin.
AB  - PURPOSE: This study was to determine whether age-related decrements in type I
      collagen synthesis occur in human eyelid skin. METHODS: Using an antibody to
      procollagen I, we investigated collagen synthetic activity in skin removed for
      cosmetic purposes from 10 white patients between the ages of 4 and 77 years.
      Eleven masked referees graded the immunostaining on a scale of 1 (most intense)
      to 10 (least intense). RESULTS: The multiple range test for rank by group
      demonstrated more intense staining in younger patients compared with older
      patients. An average correlation coefficient of 0.8432 (p < 0.05) existed between
      each of the referee's rankings. CONCLUSION: Type I collagen synthesis diminishes
      with age in eyelid skin.

PMID- 9513238
TI  - The missing muscle syndrome in blowout fractures: an indication for urgent
      surgery.
AB  - The purpose to this study was to determine whether early surgical repair is
      indicated for a severely entrapped inferior rectus muscle following orbital
      blowout fracture. We report two patients with small blowout fractures, severe
      entrapment of the inferior rectus muscle, and an absence of the inferior rectus
      muscle in multiple contiguous coronal computed tomography cuts. At surgery, we
      released the severely entrapped inferior rectus muscles with resolution of
      diplopia. We concluded that patients with the "missing muscle syndrome" require
      urgent surgical intervention and that clinician review of radiologic studies is
      always prudent.

PMID- 9513239
TI  - Prediction of late enophthalmos by volumetric analysis of orbital fractures.
AB  - The purpose of this study was to determine whether orbital volume assessment by
      computerized tomography (CT) could provide additional information for the initial
      evaluation of orbital blowout fractures and guide optimal treatment. The medical
      records of 30 patients with orbital blowout fractures, either surgically or
      conservatively managed, were retrospectively reviewed. Orbital volumetric
      analysis was then determined from digitized CT scans. Fracture-related volume
      expansion relative to the unaffected fellow orbit was correlated with motility
      deficits and location and degree of enophthalmos. Early Hertel's measurements (<
      4 weeks) were available in 21 patients and did not correlate with the computer
      volumetric values or with subsequent late enophthalmos. Late Hertel's
      measurements (> 4 weeks) were obtained in 13 of 15 nonrepaired fractures and in 5
      of 15 surgically repaired patients (late presentation; 18 patients). When seen at
      more than 4 weeks, 11 (92%) of 12 patients with > or = 13% orbital volume
      expansion manifested significant enophthalmos (> 2 mm) compared with 1 (17%) of 6
      patients with < 13% orbital expansion (p = 0.004). Fractures presenting with
      enophthalmos on initial examination had extensive medial wall involvement in
      addition to the floor fracture (p = 0.003). CT measurements of orbital volume can
      predict the final degree of late enophthalmos and may facilitate the planning of
      surgical intervention.

PMID- 9513240
TI  - LeFort I orbitotomy: a new approach to the inferonasal orbital apex.
AB  - Numerous approaches to the orbit have been elegantly described in the literature.
      One area of the orbit that remains difficult to approach with standard techniques
      is the inferonasal apex. We describe a new surgical procedure we have termed the
      LeFort I orbitotomy. The technique involves creation of a LeFort I osteotomy to
      separate the maxilla from the zygoma and nose bilaterally. The posterior
      inferomedial orbital bone is then removed and the periorbita opened. This
      approach allows a more direct, less tangential view to this area of the orbit
      than does a Caldwell-Luc approach. Wider access for tumor manipulation is gained
      than would be possible with a transnasal endoscopic approach. An illustrative
      case report is presented.

PMID- 9513241
TI  - Porous polyethylene sheet implant with a barrier surface: a rabbit study.
AB  - Soft tissue adhesion to the porous polyethylene sheet implant (PPSI) raises the
      concern of postoperative extraocular motility disturbance after orbital blowout
      fracture repairs using PPSI. A PPSI with a barrier surface (PPSI-B) has been
      developed to reduce adhesion between soft tissue and the implant. Six PPSI-B and
      six conventional PPSI were implanted under the scalps of three New Zealand white
      rabbits. The implants were harvested at 2-, 4-, and 20-week intervals. Clinical
      and histologic comparisons were made between PPSI-B and PPSI with regard to
      adhesion at the soft tissue-implant interface. Clinically, PPSI-B demonstrated
      less adhesion between soft tissue and implant compared with the conventional
      PPSI. Both types of implants demonstrated a complete fibrovascular ingrowth by 2
      weeks. Because PPSI-B causes less adhesion at the soft tissue-implant interface,
      consideration should be given to the use of PPSI-B in repairs of orbital blowout
      fractures in which extraocular muscle is exposed to the implant surface.

PMID- 9513242
TI  - Extrusion of porous polyethylene orbital implant in recurrent retinoblastoma.
AB  - High-density porous polyethylene allografts are used as orbital implants in
      reconstruction of anophthalmic sockets. The use of this material for integrated
      buried implants is rather new, and studies on removed implants from humans are
      limited. We studied the case of a 6-year-old boy with an extruded porous
      polyethylene implant due to orbital recurrence of retinoblastoma. The clinical
      and morphological features are reported. Histopathology revealed fibrovascular
      downgrowth in the outer two thirds of the sphere. Scanning electron microscopy,
      however, documented further downgrowth of fibrous tissue into the central core.
      Transmission electron microscopy depicted a spectrum of collagen fiber
      orientations to polyethylene material, ranging from perpendicular to concentric.
      Immunohistochemistry studies were inconclusive.

PMID- 9513243
TI  - Squamous cell tumors and ocular prostheses.
AB  - Conjunctival squamous cell carcinoma is an infrequent tumor. It has been reported
      to occur in association with actinic damage and chronic irritation. To the
      authors' knowledge, however, this tumor has not been reported secondary to poorly
      fitting ocular prostheses. Two patients were studied in whom conjunctival
      squamous cell carcinoma had developed. In both instances, the patient had been
      enucleated and fitted with an ocular prosthesis more than 40 years before tumor
      development. Histopathologic evaluation of each tumor revealed its squamous cell
      origin. In one of the patients, the tumor was found to be metastatic to the
      ipsilateral parotid gland, an uncommon finding. The authors attempted to identify
      risk factors that may have contributed to the development of these tumors. Aside
      from the poor fit of the prostheses, neither patient had significant risk factors
      for the development of conjunctival squamous cell carcinoma. It is concluded that
      a new, sanguineous conjunctival discharge or focal eyelid swelling after years of
      prosthetic wear may not be due to mechanical irritation alone. The onset of these
      symptoms, especially years after the initial fitting of an ocular prosthesis,
      should prompt a thorough investigation of its cause.

PMID- 9513244
TI  - Eyelid basal cell carcinoma with intracranial extension.
AB  - We describe a case of basal cell carcinoma (BCC) situated on the external upper
      margin of the right eyelid in a young man aged 28 years. The tumor was diagnosed
      as an "extended wart in a degenerative phase" and removed during reconstructive
      plastic surgery. No pathologic examination was performed. Seven years later, the
      operation was followed by a first recurrence. Pathologic examination was then
      performed, and the diagnosis was BCC. Therapy was with radiotherapy and
      chemotherapy. Subsequent recurrences were treated with radiotherapy and surgery
      (enucleation, exenteration of the orbit), but the evolution of the tumor was not
      halted. It ended 25 years after its first manifestation with the death of the
      patient of a hemorrhage of the upper airways during an operation, the aim of
      which was to reexamine the orbital cavity. The autopsy revealed intracranial
      extension of the tumor, and all the histological examinations confirmed the
      diagnosis. No histopathological feature was found that could differentiate a
      particularly aggressive nature of the tumor. Basal cell carcinoma is a tumor more
      frequently encountered in elderly patients. Its appearance in a young subject may
      cause grounds for suspicion, requiring initial radical surgical treatment and
      careful surveillance of the evolution of the lesion. This case documents the
      fatal consequences that may arise from the failure to recognize BCC in its first
      manifestation and highlights the ineffectiveness of repeated radiation and
      surgical therapy against continual recurrence.

PMID- 9513246
TI  - Osteosarcoma of the orbit associated with Paget disease.
AB  - Osteosarcoma is a common primary bone malignancy most often involving the long
      bones and occurring in the second decade of life. Orbital involvement in this
      disease process is rare and is usually due to extension of the tumor from an
      adjacent sinus cavity. Orbital osteosarcoma arising from preexisting Paget
      disease is exceedingly rare. We report the case of a 78-year-old female patient
      with Paget disease of the forehead who presented with rapidly increasing
      bilateral proptosis and visual loss for several months. Examination showed
      bilateral aphakia, decreased motility, proptosis with resistance to retropulsion,
      and tumorous infiltration of the eyelids and periorbital soft tissue. Fundus
      examination showed marked bilateral scleral indentation without overlying serous
      retinal detachment. A computed tomographic (CT) evaluation of the orbits
      demonstrated extensive soft tissue involvement of the paranasal sinuses, nasal
      cavity, periorbital soft tissue, and orbits, with compression of the optic nerve
      and globe bilaterally. Biopsy of the periorbital soft tissue demonstrated
      osteosarcoma. Radiation therapy failed to stem the progression of the disease
      process, and the patient died approximately 4 months later. Although osteosarcoma
      of the orbit associated with Paget disease is unusual, it should be considered in
      the differential diagnosis of older patients with a rapidly progressive orbital
      mass.

PMID- 9513245
TI  - Solitary fibrous tumor of the orbit.
AB  - Solitary fibrous tumor (SFT) of the orbit is a very rare lesion that may be
      misdiagnosed as fibrous histiocytoma, hemangiopericytoma, or other orbital
      tumors. We present a 62-year-old man who presented with painless proptosis, 20
      years following left eye enucleation for a presumed neurofibroma. On T2-weighted
      magnetic resonance imaging (MRI), a hypointense tumor almost filled his entire
      left orbit. There was no intracranial extension. The specimen obtained at orbital
      exenteration was consistent with the histologic, immunohistochemical, and
      electron microscopic findings of SFT. The tumor was positive for vimentin and
      CD34 staining but negative for S-100 protein and epithelial membrane antigen.
      Only nine other cases of SFT of the orbit have been documented in the literature.
      Recognition of SFT of the orbit as a distinct pathologic entity and further
      follow-up of published cases are needed to determine the prognosis of this rare
      lesion.

PMID- 9513247
TI  - Multiple myeloma involving the orbit.
AB  - Multiple myeloma is a plasma cell malignancy often associated with destructive
      skeletal lesions. Orbital involvement in multiple myeloma is rare. Risk factors
      for orbital involvement have not been established, although risk may vary with
      immunoglobulin subtype. Early detection of orbital plasmacytoma may affect
      treatment and clinical course. A case is reported of multiple myeloma without
      elevated serum immunoglobulins that involves the orbit, and the implications of
      early detection are discussed. The patient was first examined by an
      ophthalmologist 13 months after multiple myeloma was diagnosed and 5 months after
      the external appearance of an orbital tumor. Urine protein electrophoresis
      demonstrated kappa light chains. Hypergammaglobulinemia was not detected. Plain
      film roentgenography showed orbital involvement at the time of initial diagnosis.
      An impressive clinical response to external beam radiation therapy was seen.
      Attention to immunoprotein characteristics in multiple myeloma may help to
      identify risk factors for orbital involvement. Early detection may permit safer
      and equally effective treatment. All patients with multiple myeloma should
      undergo thorough ophthalmic examination at the time of initial diagnosis.

PMID- 9513248
TI  - Release of antibiotics from collagen dressing.
AB  - Our new collagen dressing has been developed recently. Three types (A, B, and C)
      of the dressing were prepared in this study. Each type contained bacitracin,
      neomycin or colistin. The antibiotic was input into: i. collagen sponge (CS)-
      type A, ii. layer of limited hydrophobicity (LLH)--type B, and iii. into both CS
      and LLH layers--type C. The final concentration of the antibiotic that resulted
      from the loading level was 2 mg/cm2 for the dressings of type A and B and 4
      mg/cm2 for the dressing of type C. The antibiotics were then extracted from the
      pieces of dressings for two days through dialysis membrane. Susceptibility of 54
      bacterial strains (S. aureus, P. aeruginosa, and Acinetobacter) isolated from
      burn wounds were tested to the three antibiotics used for preparation of the
      dressings. The results of the study evidenced that efficiency of released of
      antibiotics into the extracts depended on the kind of antibiotic and on the type
      of dressing. The concentration of the antibiotics proved to be much higher than
      MIC90 values of the bacterial isolates tested in respect to their susceptibility.
      The dressing containing mixture of the three antibiotics in two layers--CS and
      LLH is now considered as potentially effective for care of infected wounds. It
      may be useful for the treatment of infected wounds or for profilaxis of
      contaminated wounds, ensuring: i. sufficient antimicrobial activity in wound, and
      ii. optimal wound environment for the presence of collagenic biomaterial on the
      damaged tissue.

PMID- 9513249
TI  - [Treatment using Polish collagen biomaterials].
AB  - The article presents the review of all published and not published results of
      clinical investigations of new polish collagen biomaterials that have been
      registered in Poland recently. Two main medical applications of the biomaterials-
      used as hemostatic tampons and/or as biological dressings for wound care have
      been described here. The collagen sponges proved to be useful in chronic wound
      care and for hemostasis of bleeding wounds. The collagen membranes are effective
      in extensive superficial wounds care (burns, skin donor places or wounds after
      dermabrasion).

PMID- 9513250
TI  - An investigation into vascular prosthesis modified with an electron beam.
AB  - The present paper shows the results of an investigation into the effect of
      implanted electric charge on blood platelet adhesion to woven surfaces of
      "Dallon" polyester vascular prosthesis. The electrets were formed using the
      electron beam method. The assessment of the electret effect on blood platelet
      adhesion was performed on the basis of microscopic studies. It was shown that an
      implanted negative electric charge remarkably suppresses thrombocyte adhesion to
      the prosthesis surface. The electret effect was found to play a significant role
      in the process of preparing nonthrombogenic surfaces.

PMID- 9513251
TI  - [Early cellular and humoral response after vascular prosthesis implantation in
      the arterial system].
AB  - The aim of the study was to determine the level of leukocytes activation after
      the implantation of vascular graft. As an experimental model we used 20 dogs. The
      aorto-iliac unilateral graft (dacron 6 mm) was implanted to all animals. The
      adhesion and migration of the leukocytes was estimated postoperatively by
      scintigraphy using Tc99 labeled leukocytes. The increased migration and adhesion
      was found in both proximal and distal anastomoses till the 30th postoperative day
      and it was more intensive in the distal anastomosis.

PMID- 9513252
TI  - [Clinical evaluation of a polyester vascular prosthesis impregnated with albumins
      from material of the Vascular Surgical Clinic AM in Wroclaw in the years 1994
      1997. Introductory report].
AB  - The aim of this work was clinical evaluation of impregnated (albumins) prostheses
      of Polish production. Those prostheses were compared with polyester knitted
      vascular prostheses. We evaluated a group of 48 patients to whom prostheses
      covered with albumins were implanted and 52 patients to whom nonimpregnated
      prosthesis was implanted in 1994-1997. The prostheses were implanted in
      aortofemoral segment. The achieved results prove the good quality of the
      impregnated prosthesis and its high value for vascular reconstructive surgery.

PMID- 9513253
TI  - [Use of a silicone prosthesis in two-staged reconstructive surgery of flexor
      tendons in fingers].
AB  - Since the time of introduction in the sixties by Hunter from Philadelphia of
      temporary prosthesis of tendon which was a silicone rod reinforced with dacron it
      has come into regular clinical usage enabling reconstruction of large injuries of
      tendons of flexors of fingers--particularly in the sheath area. In the work the
      analysis of the remote results after two-staged reconstructive operations of
      tendons of flexors of fingers is presented. The clinical material includes 68
      patients whom in 1982-1993 tendons were reconstructed with the above mentioned
      method in the Clinic of Injury Surgery of Medical Academy in Wroclaw. The results
      of treatment were evaluated according to Buck-Gramcko scale in three groups. In
      group I (patients with isolated tendons injury) 28% very good, 17% good and 55%
      satisfactory results were achieved. In group II (patients with tendons and nerves
      injury) 15% very, good, 30% good, 45% satisfactory and 10% unsatisfactory results
      were achieved. In group III (patients with tendons, nerves and bones injury) 4%
      very good, 20% good 30% satisfactory and 46% unsatisfactory results were
      achieved. Also proportional loss of muscle strength of the operated fingers,
      degree of return of two-punctual feeling in case of additional injury of finger
      nerves were evaluated. The analysis of treatment results depending on the number
      of injured fingers, method of primary dressing and on the time of undertaking the
      secondary reconstruction was carried out. On the basis of the carried out tests
      and their analysis the optimal method of treatment of patients qualified for two
      staged reconstructions of tendons of flexors of fingers was presented.

PMID- 9513254
TI  - An assessment of athrombogenic properties of electret polyethylene film.
AB  - This paper shows the results of an investigation into the effect of an electric
      charge on blood platelet adhesion. All of the experiments were made on a
      polyethylene film. The electrets were formed using the electron beam method. The
      assessment of the electret effect on blood platelet adhesion was performed
      microscopically. It was found out that an electric charge plays a major role in
      the process of adhesion of blood morphological elements.

PMID- 9513255
TI  - [Changes in the level of interleukin-1 beta and interleukin-6 after implantation
      of selected medical materials. Introductory report].
AB  - Evaluation of biomaterials with the help of routine methods not always allow full
      and explicit stating of their toxicity. That is why we still seek new methods of
      evaluation of biocompatibility on the cellular level. Usage of changes in
      activity of interleukin after biomaterials implantation creates such a
      possibility. The aim of this work as use of changes in activity of cytokines IL-1
      beta and cytokines IL-6 for evaluation of biocompatibility of chosen medical
      materials. The tests were made on mice to whom polyester and aramid fibres as
      well as discs of rubber drains were implanted into the peritoneal cavity.
      Evaluation of the changes of the level of interleukin-1 beta and interleukin-6
      was made in the fluid from the peritoneal cavity 3, 7, 14 and 21 days after
      implantation. Introductory tests of changes in the level of IL-1 beta and IL-6
      after implantation of biomaterials with different degree of biocompatibility
      allow to assume that testing their activity may be useful in evaluation of their
      toxic effect.

PMID- 9513256
TI  - [Comparison of peritoneal patch and vascular prosthesis monitored with isotopes
      and parameters of humoral and cell mediated response].
AB  - The aim of this experimental study was to assess the reaction of peritoneal patch
      and vascular graft after implantation in arterial system. We compare complement
      haemolytic activation CH-50%, serum elastase and scintigraphy using Tc99 labeled
      leukocytes. There were significant differences in parameters of humoral and cell
      mediated response between implantation of peritoneal patch and vascular graft.
      Twelve months later histological examination was made to determine healing
      processes of implanted materials. The results of this study are encouraging and
      confirm benefits of peritoneal patch in vascular surgery creating a new
      possibilities of angioplasty.

PMID- 9513258
TI  - [Effects of closed-circuit breathing apparatus on respiration and metabolism].
AB  - The purpose of the study was to evaluate the influence of hyperoxia and
      hypercapnia on respiration and metabolism during a steady-state exercise.
      Thirteen healthy subjects were examined during bicycle-ergometer rides at
      approximately 50% VO2max under four different breathing gas conditions: 1) room
      air (control); 2) 40% oxygen; 3) 3% carbon dioxide; 4) 40% oxygen and 3% carbon
      dioxide. Hyperoxia, with or without hypercapnia, decreased respiratory
      ventilation and carbon dioxide elimination significantly. On the other hand,
      oxygen uptake in hyperoxia was not significantly different from that of normoxia.
      Hypercapnia increased respiratory ventilation more than 30% compared to
      normocapnia, but it did not change oxygen uptake and carbon dioxide elimination
      significantly.

PMID- 9513257
TI  - [Experiments on new synthetic and non-absorbable surgical threads].
AB  - The aim of this work was a complex evaluation of synthetic non-absorbable
      surgical threads of the latest, so called 3rd generation: Novafil, Monolene and
      Fore-Tex. Biological tests in vivo were carried on 90 white rats of the Wistar
      tribe. The animals were divided into three experimental groups depending on the
      kind of the implanted surgical thread. Moreover, taking into account the place of
      implantation of the tested threads, each group was divided into two sub-groups
      containing 15 rats each. Operations were carried on in the conditions of surgical
      aseptics implanting the tested threads into the striated muscles of the back and
      into the liver in order to make macroscopic and microscopic tests of tissue
      reaction and also into the peritoneal cavity in order to carry out resistance
      tests after a different time of the threads stay in the tissues. The animals'
      sections were carried out 7, 14, 21, 90 and 180 days after the implantation of
      the above mentioned threads. On the basis of many year's experience of The
      Institute of Experimental Surgery and Biomaterial Research and review of 52 works
      of specialistic literature I have chosen the following additional criteria of
      evaluation: tests of stability of surgical knot, tests of resistance in the knot
      to break, tests of surgical convenience including easiness of carriage of the
      tested threads through the tissues, flexibility, absorbability, possibility of
      coiling of a loose segment of threads, electrifying and the security of the knot.
      Tissue reaction was based on macroscopic and microscopic tests. In macroscopic
      tests we paid attention to the course of healing of the threads in
      transversostrated muscles and in liver tissue paying attention to the behaviour
      of the organs of o the abdominal cavity during the section. Characteristic
      pictures are documented by photographs. Microscopic tests consisted on making
      histological samples of the threads together with the surrounding tissues.
      Microscopic evaluation was carried on 1080 samples using punctual of tissue
      reaction. The used punctual system for describing tissue reaction after
      implantation of non-absorbable surgical threads includes the number and degree of
      condensation of cells in the vicinity of the implanted thread, the width of the
      sphere of the inflammatory reaction and the histological analysis of the cells
      type. The used punctual evaluation enables objective evaluation of the tested
      histological samples. Variously evaluated threads Novafil, Monolene and Gore-Tex
      are characterised by large resistance, very good surgical convenience and minimal
      tissue reaction. On the basis on the carried out laboratory tests and tests on
      animals the following conclusions were made: 1. Non-absorbable surgical threads
      Novafil, Monolene, Gore-Tex do not make organism changes and heal with minimal
      tissue reaction what proves their high biocompatibility. 2. The used punctual
      evaluation of the tissues reaction after implantation of non-absorbable surgical
      threads allows complex and objective classification of the degree of tissues
      reaction. 3. Monofibrous surgical threads Novafil and Monolene do not lose
      resistance to break in the knot. 4. Surgical threads Novafil and Monolene are
      characterized by very good security of the knot while threads Gore-Tex have large
      flexibility and small coefficient of friction, which is the cause of weak
      security of the knot in case of fastening under tension. 5. Tissues reaction
      after implantation of synthetic non-absorbable surgical threads Novafil, Monolene
      and Gore-Tex is smaller in comparison with the tissues reaction which were caused
      by non-absorbable surgical threads tested in the former years. 6. In comparison
      with the non-absorbable surgical threads tested in the former years, very good
      surgical convenience, lack of loss of resistance to break in the knot and minimal
      tissues reaction give the basis to classify threads Novafil, Monolene and Gore
      Tex to improved non-absorbable surgical threads of the new generation

PMID- 9513259
TI  - [Effect of walking during all weekdays, holidays, and at work on mental and
      physical health in workers].
AB  - In order to clarify the effects of walking under various psychosocial and
      occupational conditions on psychophysiological health, we examined the
      relationship between the number of steps walked in several situations, such as on
      all weekdays, at work, and over the weekend, and the results of medical checkups,
      psychological tests, Breslow's 7 health practices, and other attitudes toward
      walking as well as health by using a pedometer in a certain manufacturing
      company. Most of the workers estimated their usual number of steps walked as
      being less than actual levels on both weekdays and holidays. Generally, the
      increased number of steps walked was significantly correlated with increased HDL
      cholesterol levels, and decreased Triglyceride levels. Contrary to such physical
      effects, there were more variations with respect to the relationship between
      walking and psychological health. Moreover, the development of a walking habit at
      work resulted in some factors becoming worse, such as relaxation, trait anxiety,
      and serum AST levels when compared to those on all weekdays and over the weekend.
      In conclusion, it is necessary to consider several situations in which workers
      usually walk and we must also practice counseling and education for health
      promotion, to promote walking for health care in the workplace.

PMID- 9513260
TI  - [Patterns of utilization of external employee assistance program--analysis of
      employees who have their psychiatrists].
AB  - The purpose of this paper is to clarify some patterns of utilization of an
      external employee assistance program (EAP) we have conducted for other public and
      private facilities in the Tokyo Kenbikyoin Foundation between April, 1986 and
      December, 1996. The subjects were 26 men and 12 women in 7 facilities under the
      following conditions: (1) Employees who have already had their own psychiatrists
      at the first interview of the external EAP; (2) Facilities utilize the EAP for
      two or more employees who met the first criterion. As a result, utilization
      patterns differed depending on medical staff's attitude toward the external EAP.
      There was a significant difference according to sex. The rate for men was 54% in
      worksites where medical staff understood this external program (worksite A1) and
      93% in worksites where they did not (worksite A2-3, B). As to expectations for
      the program, there were more consultations for organizational measurements (63%)
      in worksite A1, while less organizational matters (27%) and more personal
      complains about their psychiatrists in the worksite A2-3, and B. These results
      suggest that the involvement of medical staff is the key to utilizing the
      external EAP effectively.

PMID- 9513261
TI  - [Carbon monoxide poisoning during construction of a natural gas supply pipeline].

PMID- 9513262
TI  - Molecular aspects of the E. coli nucleoid protein, H-NS: a central controller of
      gene regulatory networks.
AB  - The nucleoid-associated protein H-NS has a central role in the structuring and
      control of the enteric bacterial chromosome. This protein has been demonstrated
      to contribute to the regulation of expression for approximately thirty genes. In
      this article, the molecular aspects of H-NS structure and function are briefly
      reviewed. H-NS contains at least two independent structural domains: a C-terminal
      domain, involved in the DNA-protein interactions, and a N-terminal domain, likely
      involved in protein-protein interactions. Recent reports have revealed that H-NS
      is a key factor in a multi-component gene regulatory system. Factors have now
      been discovered which can backup or antagonise H-NS action at certain promoters.
      These recent findings are summarised and discussed in relationship to the role of
      H-NS in DNA packaging and nucleoid structure.

PMID- 9513263
TI  - Isolation of a hemin and hemoglobin binding outer membrane protein of Vibrio
      vulnificus biotype 2 (serogroup E).
AB  - The eel pathogen Vibrio vulnificus biotype 2 (serogroup E) is able to use hemin
      (Hm) or hemoglobin (Hb) as the sole iron source for growth in vitro and in vivo.
      The mechanism of heme-iron acquisition in this bacterium requires a direct
      interaction through binding sites on the bacterial surface (constitutive outer
      membrane proteins). Using affinity chromatography techniques, a unique protein of
      around 36.5 kDa was isolated from cell envelopes of E86 strain regardless of the
      affinity ligand used, hemoglobin or hemin. This protein was purified from both
      iron-enriched and iron-restricted grown cells. These results support the
      hypothesis that in this pathogen Hm- and Hb-iron acquisition is mediated by a
      common protein receptor which recognizes the heme prosthetic group of Hb.

PMID- 9513264
TI  - A broad-host-range mobilizable shuttle vector for the construction of
      transcriptional fusions to beta-galactosidase in gram-positive bacteria.
AB  - A low-copy-number vector designated pTCV-lac has been constructed to provide a
      convenient system to analyze regulatory elements in Gram-positive bacteria. The
      main components of this vector are: (i) the origins of replication of pACYC184
      and of the broad-host-range enterococcal plasmid pAM beta 1, (ii) erythromycin-
      and kanamycin-resistance-encoding genes for selection in Gram-negative and Gram
      positive bacteria, (iii) the transfer origin of the IncP plasmid RK2, and (iv) a
      promoterless beta-galactosidase-encoding lacZ gene with a Gram-positive ribosome
      binding site. This 12 kb plasmid is present in Gram-positive hosts in three to
      five copies per chromosome equivalent and contains three unique cloning sites
      (EcoRI, SmaI, BamHI) for cloning of DNA inserts upstream of the lacZ gene.
      Plasmid pTCV-lac and derivatives carrying different promoter fragments have been
      transferred by conjugation from an Escherichia coli IncP mobilizing donor strain
      to Bacillus subtilis, Listeria monocytogenes, Enterococcus faecalis, and
      Streptococcus agalactiae. These plasmids were structurally stable in these hosts
      and the corresponding promoter activities, quantitated by the determination of
      the beta-galactosidase specific activities, were found to cover at least a 100
      fold range in beta-galactosidase values. These results indicate that pTCV-lac
      should be useful for analysis of gene regulation in a wide range of Gram-positive
      bacteria.

PMID- 9513265
TI  - RFLP-PCR analysis of the aroA gene as a taxonomic tool for the genus Aeromonas.
AB  - The aroA gene has been identified as a target in screening for the presence of
      most Aeromonas species so far described by PCR. Synthetic oligonucleotide primers
      of 24 and 25 nucleotides were used by PCR assay to amplify a sequence of the aroA
      gene, which encodes 3-phosphoshikimate-1-carboxyvinyltransferase, a key enzyme of
      aromatic amino acids and folate biosynthetic pathway. A 1236-bp DNA fragment,
      representing most of the aroA gene, according to the nucleotide sequence of A.
      salmonicida, was amplified from all Aeromonas species tested, which represented
      most of the 14 hybridization groups. HaeII digestion of the 1236-bp fragment
      generated a restriction fragment length polymorphisms which could be used as a
      powerful tool for identification of aeromonads to the genus level.

PMID- 9513266
TI  - The particulate methane monooxygenase gene pmoA and its use as a functional gene
      probe for methanotrophs.
AB  - The particulate methane monooxygenase gene pmoA, encoding the 27 kDa polypeptide
      of the membrane-bound particulate methane monooxygenase, was amplified by PCR
      from DNA isolated from a blanket peat bog and from enrichment cultures
      established, from the same environment, using methane as sole carbon and energy
      source. The resulting 525 bp PCR products were cloned and a representative number
      of clones were sequenced. Phylogenetic analysis of the derived amino acid
      sequences of the pmoA clones retrieved directly from environmental DNA samples
      revealed that they form a distinct cluster within representative PmoA sequences
      from type II methanotrophs and may originate from a novel group of acidophilic
      methanotrophs. The study also demonstrated the utility of the pmoA gene as a
      phylogenetic marker for identifying methanotroph-specific DNA sequences in the
      environment.

PMID- 9513267
TI  - Nucleotide sequence and molecular characterization of a gene encoding GTP-binding
      protein from Streptococcus gordonii.
AB  - A 1286-bp fragment of chromosomal DNA from Streptococcus gordonii strain Challis
      was cloned and sequenced. The gene sgg consisted of 897-bp nucleotides encoding a
      299-amino acid polypeptide (33,200 Da). The deduced amino acid sequence exhibited
      significant similarity to Era, G protein of Escherichia coli. The nucleotide
      binding assay demonstrated that recombinant Sgg bound [32P]GTP but not [32P]ATP,
      [32P]CTP, or [32P]UTP. These findings indicate that Sgg is a member of the G
      protein superfamily in the genus Streptococcus.

PMID- 9513268
TI  - Analysis of the G93E mutant allele of KpsM, the membrane component of an ABC
      transporter involved in polysialic acid translocation in Escherichia coli K1.
AB  - KpsM is an integral membrane protein involved in the translocation of the
      polysialic acid capsule of Escherichia coli K1. The kpsMG93E allele is a point
      mutation in the first cytoplasmic loop (Cl) of KpsM which partially disrupts
      translocation of the capsule. While producing polymer of wild-type length,
      strains harboring the G93E allele exhibit a decreased production of capsular
      polymer and a reduced rate of polymer translocation to the cell surface.

PMID- 9513269
TI  - Identification of restriction barriers in Pasteurella multocida.
AB  - Several naturally occurring antibiotic resistance plasmids were isolated from
      Pasteurella multocida type D strains. One plasmid, pPM1, was used to study
      transfer of DNA among P. multocida strains, and could be transferred into
      Escherichia coli and some P. multocida isolates. However, pPM1 could only be
      transferred into the toxigenic P. multocida LFB3 at very low frequency. Plasmid
      recovered from the electrotransformants could be transferred to LFB3 at high
      frequency. These plasmid DNAs were resistant to PstI, and sensitive to DpnI
      digestion. Sensitivity to DpnI was common to all the P. multocida DNAs, but
      resistance to PstI was confined to LFB3. Plasmid pPM1 treated with PstI methylase
      was able to transform LFB3 at an increased frequency compared to unmethylated
      DNA, suggesting that LFB3 has a restriction system which cleaves at or near PstI
      sites.

PMID- 9513270
TI  - The effects of mutation of the anr gene on the aerobic respiratory chain of
      Pseudomonas aeruginosa.
AB  - The anr gene of Pseudomonas aeruginosa encodes a transcriptional regulator of
      anaerobic gene expression, homologous to the Fnr protein of Escherichia coli. We
      report here that Anr has a role in regulating the activity of the aerobic
      respiratory chain of P. aeruginosa. Strains with internal deletions in their anr
      gene had lowered levels of membrane bound cytochromes whilst the activity of the
      cytochrome c oxidase, cytochrome co (likely to be a cytochrome cbb3-type
      oxidase), and the cyanide-insensitive respiratory pathway was markedly higher
      than in the wild-type strains. These data, and the finding that provision of
      multiple copies of the anr gene led to severe repression of these respiratory
      activities, suggest that Anr is a repressor of aerobic respiratory pathways and
      possibly the terminal oxidases themselves. In contrast, Anr activated cytochrome
      c peroxidase, a respiratory chain linked enzyme induced under low oxygen
      conditions.

PMID- 9513271
TI  - Characterization of the presumptive phosphorylation sites of the Bacillus
      subtilis glucose permease by site-directed mutagenesis: implication in glucose
      transport and catabolite repression.
AB  - Bacillus subtilis utilizes glucose as the preferred source of carbon and energy.
      Glucose is transported and concomitantly phosphorylated by the glucose permease
      (PtsG) of the phosphoenolpyruvate:sugar phosphotransferase system. The phosphate
      is transferred from enzyme I via HPr and domains IIA and IIB of the glucose
      permease to the sugar. In this study mutants affected in the putative
      phosphorylation sites of glucose permease were constructed and the effect on
      sugar transport and glucose repression tested. Phosphorylation of both domains
      IIAGlc and IIBGlc is required for efficient glucose transport and repression of
      beta-xylosidase and the bglPH operon.

PMID- 9513272
TI  - Bordetella bronchiseptica has a BvgAS-controlled cytotoxic effect upon
      interaction with epithelial cells.
AB  - The interaction between the respiratory pathogen Bordetella bronchiseptica and
      epithelial cells was studied. After 2-3 h, B. bronchiseptica strains exerted a
      strong cytotoxic effect on HeLa cells which was evident by rounding of the cells
      and detachment from the substrate and which ultimately resulted in total
      disintegration of the host cell. Production of this cytotoxic activity appeared
      to be regulated by the BvgAS sensory transduction system, which coordinately
      regulates many B. bronchiseptica virulence factors, since bacteria cultured in
      the presence of sulfate anions, inhibitors of the BvgAS response, did not exhibit
      this effect. Furthermore, spontaneous phase variants of B. bronchiseptica strains
      adhered to HeLa cells but were not cytotoxic. The cytotoxic component is
      presumably not secreted because the bacterial culture supernatant was not
      cytotoxic for HeLa cells. Besides HeLa cells other human epithelial cell lines
      such as Chang cells, larynx HEp-2 cells and lung NCI-H292 cells were sensitive to
      the cytotoxic activity of B. bronchiseptica. These results suggest the presence
      of a novel BvgAS-regulated virulence factor in B. bronchiseptica.

PMID- 9513273
TI  - Mutation thi81 causing a deficiency in the signal transduction of thiamine
      pyrophosphate in Saccharomyces cerevisiae.
AB  - We isolated a strain carrying a recessive constitutive mutation (thi81) for the
      expression of thiamine metabolism in Saccharomyces cerevisiae. The thi81 mutant
      exhibits significant thiamine transport, thiamine-repressible acid phosphatase (T
      rAPase) activities and significant activities of enzymes involved in thiamine
      biosynthesis which are repressed in the wild-type strain in medium supplemented
      with thiamine (2 x 10(-7) M). The thi81 mutant exhibited the same level of
      thiamine pyrophosphokinase activity and intracellular thiamine pyrophosphate
      concentration as the wild-type strain in medium supplemented with exogenous
      thiamine. The mutant strain constitutively produced PHO3 mRNA encoding T-rAPase
      in medium supplemented with thiamine. These results suggest that the thi81 mutant
      lacks a negative factor involved in the regulation of the genes encoding proteins
      involved in yeast thiamine metabolism.

PMID- 9513274
TI  - Determination of genetic diversity within the genus Bifidobacterium and
      estimation of chromosomal size.
AB  - Pulsed-field gel electrophoresis was proven to be an efficient means of
      differentiating 25 strains of Bifidobacterium obtained from culture collections.
      XbaI, SpeI, DraI restriction enzyme profiles indicated genomic heterogeneity
      among strains. When seven human isolates of bifidobacteria were compared using
      the same methods, two individual banding patterns were obtained. However, despite
      its discriminatory potential, pulsed-field gel electrophoresis was shown to be of
      no value in taxonomic identification. Genomic sizes estimated for eight
      Bifidobacterium strains ranged from 1.5 Mb to 2.1 Mb.

PMID- 9513275
TI  - An agarose-in-plug bridge method to study chemotaxis in the Archaeon
      Halobacterium salinarum.
AB  - A simple agarose-in-plug bridge method was developed to study chemotaxis in the
      Archaeon Halobacterium salinarum. Preheated liquid agarose solution with
      chemoeffectors is pipetted in the middle of a microscope slide bridge,
      constructed by placing two plastic strips 16 mm apart. A coverslip is immediately
      placed over the agarose. The solidified agarose plug is completely encircled with
      the halobacterial cell suspension. Within a certain time concentrated
      halobacteria were seen as a ring at the edge of the agarose plug containing
      attractant amino acids and the control growth medium. Chemotaxis mutant Pho60
      cells do not accumulate either around the attractants or around the growth
      medium. The kinetics of the ring formation can be readily videotaped or
      photographed using either phase-contrast or dark-field microscopy.

PMID- 9513276
TI  - Carbons from choline present in the phospholipids of Pseudomonas aeruginosa.
AB  - The phospholipid composition of Pseudomonas aeruginosa grown in a mineral medium
      with choline as the carbon source was: phosphatidylethanolamine, 71.6 +/- 1.4%;
      phosphatidylglycerol, 11.8 +/- 0.4%; diphosphatidylglycerol, 0.8 +/- 0.4%;
      phosphatidic acid, 2.4 +/- 0.6%; lysophosphatidylethanolamine, 1.6 +/- 0.3%;
      phosphatidylcholine 7.9 +/- 0.3%; lysophosphatidylcholine, 3.9 +/- 0.7%. The
      molar ratio between the acidic and the neutral phospholipids was 0.18.
      Radiolabeling experiments with [methyl-14C]choline or [1,2-14C]choline carried
      out in cell suspension from bacteria that were grown in the presence of choline
      as the sole carbon source demonstrated that the carbons of the N-methyl groups of
      choline contributed to the synthesis of fatty acids while the carbons comprising
      the backbone of choline were used for the synthesis of glycerol.

PMID- 9513277
TI  - Development of a polymerase chain reaction assay for Mycoplasma salivarium by
      using the nucleotide sequence within aminopeptidase My gene.
AB  - A polymerase chain reaction assay for a 278-nucleotide DNA fragment within
      aminopeptidase My gene of Mycoplasma salivarium was developed. The assay
      amplified M. salivarium DNA, but did not amplify DNAs of other mollicutes,
      bacteria and mammalian cells. The detection limit of the assay was 10 fg of DNA,
      approximately equivalent to 10 organisms.

PMID- 9513278
TI  - The cell wall-less rickettsia Eperythrozoon wenyonii is a Mycoplasma.
AB  - The 16S rRNA gene of Eperythrozoon (Haemobartonella) wenyonii, a wall-less
      hemotrophic prokaryote currently classified as a rickettsia, was sequenced to
      determine the relationship of this organism to other wall-less prokaryotes.
      Comparison to the GenBank data base showed that this hemotrophic organism is a
      Mycoplasma (family Mollicutes). Phylogenetic analysis of 16S rRNA genes indicated
      that this and other recently sequenced 16S rRNA genes of hemotrophic bacteria
      form a new, separate branch which shares a node in common with the pneumoniae
      group of mycoplasmas. This result will require that Eperythrozoon wenyonii be
      reclassified as a Mycoplasma. A main point of this study is that this and related
      hemotrophic bacteria represent an entirely new group of pathogens among the
      mycoplasmas.

PMID- 9513279
TI  - Cyanobacterial tRNA(Leu)(UAA) group I introns have polyphyletic origin.
AB  - Self-splicing group I introns in tRNA anticodon loops have been found in diverse
      groups of bacteria (alpha, beta purple bacteria and cyanobacteria). In
      particular, the cyanobacterial tRNA(Leu)(UAA) group I introns have attracted
      considerable attention because of their presumed ancient origin and immobility.
      In this work, however, we identified tRNA(Leu)(UAA) group I introns in six out of
      16 closely related isolated belonging to the cyanobacterial genus Microcystis.
      Interestingly, these introns are more closely related to the group I introns
      identified in the alpha and beta purple bacteria (located in tRNA(Arg)(CCU) and
      tRNA(Ile)(CAU), respectively) than to other cyanobacterial introns. Our sequence
      comparison and phyletic reconstruction suggest lateral transfer of the intron
      (possibly trough mobility), and a polyphyletic origin of cyanobacterial
      tRNA(Leu)(UAA) group I introns.

PMID- 9513281
TI  - Effect of the column length on the characteristics of the packed bed and the
      column efficiency in a dynamic axial compression column.
AB  - The axial homogeneity of preparative-scale chromatography columns was studied by
      measuring the overall properties of similar columns differing only by their
      lengths. The properties investigated were the packing density, the external
      porosity, the permeability and the column efficiency. Two different materials
      were used, one made of large, irregular silica particles compressed under either
      high or a low degree of stress; the other of small, spherical and rigid
      particles. The columns made with the spherical particles were more homogeneous,
      had a higher external porosity and specific permeability, and a higher efficiency
      than those made with the irregular ones. For this latter material, the columns
      prepared with a low level of stress were better than those compressed under high
      stress. The latter ones experienced extensive particle breakage. These results
      indicate that the long columns are heterogeneous in their axial direction.

PMID- 9513280
TI  - Refining the scale-up of chromatographic separations.
AB  - The use of heavily loaded columns and complex processing conditions makes scale
      up of chromatographic separations a non-trivial process. The wide ranges of
      process conditions that must be investigated demands that a large number of
      preliminary experiments must usually be made in small columns and laboratory
      scale work stations. These preliminary data can be biased by improper column
      packing, poor distributors and dispersion in auxiliary apparatus, and it is
      important to understand these disturbing factors in detail. Moreover, it is
      precisely at this macroscopic level that our understanding of the chromatographic
      process is weakest, for large columns as well as small. This paper addresses
      three of these factors: Efficient elimination of peripheral effects and
      characterization of both header flow distribution and packing non-uniformity.
      This will be done using a variety of experimental and analytical approaches
      including nuclear magnetic resonance imaging, computational fluid dynamics and
      mass transfer, and careful experimentation.

PMID- 9513282
TI  - Comparing the optimum performance of the different modes of preparative liquid
      chromatography.
AB  - A comparative study of the optimization of the different modes of the preparative
      separation of binary mixtures by liquid chromatography is presented. Band
      profiles were calculated by means of the equilibrium-dispersive model of
      chromatography in the cases of isocratic elution, gradient elution, and
      displacement chromatography. The objective function to be maximized was the
      product of the production rate and the recovery yield. The production rate was
      calculated using the same definition of the cycle time in all cases. This common
      definition accounts for column regeneration after each run in each mode of the
      separation. The calculations reveal that the number of experimental parameters to
      be adjusted to achieve optimum separations is relatively small. The major
      parameters are the loading factor and the number of theoretical plates, besides
      the displacer concentration in displacement chromatography, or the gradient
      steepness in gradient elution. The relative advantages of the different modes of
      preparative chromatography are discussed.

PMID- 9513283
TI  - A novel technology for packing and unpacking pilot and production scale columns.
AB  - A new method of packing and unpacking large scale chromatography columns is
      described. This involves use of a 3-position valve that can inject chromatography
      media into a closed column thereby packing it. This same valve in another state
      is then used to unpack the column. Heights equivalent to a theoretical plate and
      asymmetry factors of packs on columns from 280 to 800 mm diameter are discussed.

PMID- 9513284
TI  - Effect of radial gradient of temperature on the performance of large-diameter
      high-performance liquid chromatography columns. I. Analytical conditions.
AB  - The performance of a large-diameter chromatographic column can be drastically
      reduced when the solvent enters the column at a temperature different from that
      of the wall of the column. A radial temperature gradient inside the column will
      affect the physical properties of the solvent and the chromatographic behaviour
      of the solute resulting in a deformation of the band profile. A mathematical
      model is proposed to take into account the effect of a radial gradient of
      temperature in a large-diameter column on the chromatographic peak shape under
      linear conditions. The model is then compared with experimental results in
      preparative columns of different sizes. A good agreement between experiment and
      theory has been found showing a serious effect of thermal conditions on
      separation quality, depending on the column size. It is also demonstrated that a
      small difference of temperature can be helpful to compensate practical effect of
      frits and distribution of the sample at the extremities of the packed bed.
      Finally, it demonstrates the necessity to perform efficiency measurement under
      different thermal conditions to have a good comparison between columns.

PMID- 9513285
TI  - Closed-loop recycling with periodic intra-profile injection: a new binary
      preparative chromatographic technique.
AB  - Closed-loop recycling with periodic intra-profile injection (CLRPIPI) is a binary
      chromatographic separation technique. It is similar to simulated moving bed
      chromatography in that sample is injected into the interior of the circulating
      chromatographic profile. Although the CLRPIPI process is repetitive, it is
      different from SMB in that CLRPIPI is not continuous. It is shown that the
      CLRPIPI process reaches a steady state and that high purity fractions can be
      collected.

PMID- 9513286
TI  - Optimization of the recovery yield and of the production rate in overloaded
      gradient-elution reversed-phase chromatography.
AB  - To investigate the effects of various parameters on the production rate and on
      the recovery yield in overloaded reversed-phase gradient-elution chromatography,
      band profiles of binary mixtures of phenol and o-cresol were calculated using the
      experimental parameters of the distribution isotherms determined by binary
      frontal analysis. The effects of the feed volume and of the steepness of a
      continuous gradient (gradient time) of methanol in aqueous-organic mobile phases
      on the separation were studied. If the sample feed in a solvent with weak elution
      strength is used, combined effects of on-column enrichment, frontal
      chromatography and sharpening of the later eluted bands may enhance the
      production rate and the recovery yield. Steep continuous gradients offer better
      results than isocratic elution if the feed is dissolved in water and injected
      into the mobile phase with a higher elution strength, because larger volumes of
      dilute feed can be separated with high recovery yields.

PMID- 9513287
TI  - Characterisation of ANX Sepharose 4 Fast Flow media.
AB  - ANX Sepharose 4 Fast Flow (low sub) and ANX Sepharose 4 Fast Flow (high sub) are
      two new media developed at Amersham Pharmacia Biotech. They are weak anion
      exchangers with different amounts of tertiary amine groups attached via a spacer
      arm to Sepharose 4 Fast Flow. They have been characterised by the separation of
      some model proteins under different conditions and by determination of
      breakthrough capacities for proteins of different molecular masses. Functional
      performance after storage in different solutions at ambient temperature has been
      monitored. Carbon release after storage at different pH and temperatures has been
      measured using the total organic carbon technique. The selectivity results show
      that these new media are interesting complements to already existing Fast Flow
      anion exchangers. They are very stable and can be especially useful in
      applications involving the purification of high-molecular-mass proteins.

PMID- 9513288
TI  - Importance of heat of adsorption in modeling protein equilibria for overloaded
      chromatography.
AB  - The heat of adsorption and its dependence on surface coverage has been measured
      calorimetrically for protein ion-exchange systems of bovine serum albumin and
      ovalbumin on an anion-exchanger. Experimental data show that protein adsorption
      is endothermic for both systems which suggests that the process is entropically
      driven. Also, heat of adsorption decreased with coverage indicating repulsive
      lateral interactions between adsorbed proteins. The protein adsorption isotherms
      were modeled with the nonideal surface solution model. This analysis revealed
      that it is essential to include the entropic contribution in modeling equilibrium
      behavior. An empirical method for incorporating this effect has been presented.

PMID- 9513289
TI  - Frontal chromatography of proteins. Effect of axial dispersion on column
      performance.
AB  - A mathematical model describing the dynamic adsorption of proteins in columns
      packed with spherical porous adsorbent particles is used to study the effect of
      axial dispersion on the performance of chromatographic systems. The values of the
      axial dispersion coefficient, DL, are estimated from a correlation based on a
      model describing axial dispersion in packed beds that provides satisfactory
      results when compared with experiment. Simulations of frontal chromatography in
      systems including axial dispersion and in systems without axial dispersion are
      made and compared to determine the effect of axial dispersion on the efficiency
      of the adsorption process; also, the system parameters that influence axial
      dispersion are examined. It is found that the reduction in the efficiency of the
      adsorption process due to axial dispersion is small (< 1%) for columns of length
      10 cm or greater. However, for short columns, this efficiency reduction can be as
      large as 10%. Increasing the adsorbent particle diameter, dp, increases the
      magnitude of the reduction in efficiency due to axial dispersion; the effect of
      increasing the adsorbent particle diameter, dp, is much more pronounced in a
      short column than in a long column.

PMID- 9513290
TI  - Development of a downstream process for the isolation and separation of
      monoclonal immunoglobulin A monomers, dimers and polymers from cell culture
      supernatant.
AB  - The isolation and separation of the molecular variants of monoclonal IgA from
      cell culture supernatants is possible using several filtration and ion-exchange
      chromatography steps, followed by size-exclusion chromatography for the actual
      separation of the molecular variants. The latter step is especially time
      consuming and laborious. This report presents possible improvements of the
      procedure. Use of the displacement rather than the elution mode may render the
      ion-exchange step more productive (higher product concentrations and space-time
      yield). For the final separation of the molecular variants, hydroxyapatite (HA)
      elution chromatography can serve as an alternative to size-exclusion
      chromatography. By using an optimized, complex phosphate gradient, the IgA dimers
      can be separated quantitatively from the monomers and higher oligomers. It may in
      individual cases be necessary to use a size-exclusion polishing step to reach the
      required final degree of purity, however, the amount of material to be processed
      is reduced to such an extend by the HA-step, that the overall process is still
      more productive. Buffer pH and flow-rate as well as the stationary phase material
      used were additional factors considered during the optimization of the HA elution
      chromatography. HA-displacement chromatography resulted only in a concentration
      of the overall IgA fraction, but not in a separation of the molecular forms.

PMID- 9513291
TI  - Preliminary study on hydrophobic interaction chromatography of Chromobacterium
      viscosum lipase on polypropylene glycol immobilized on Sepharose.
AB  - The purification of Chromobacterium viscosum lipase was performed using a
      polypropylene glycol-Sepharose gel. The influence of the mobile phase composition
      on the chromatographic behaviour of Chromobacterium viscosum lipase was studied
      and it was found that the retention of lipase depends on the salt used and
      increased with ionic strength. Using 20% (w/v) ammonium sulphate in the eluent, a
      total retention of lipase on the column was obtained.

PMID- 9513292
TI  - Micropreparation of tissue collagenase fragments of type I collagen in the form
      of surfactant-peptide complexes and their identification by capillary
      electrophoresis and partial sequencing.
AB  - Combination of standard approaches like pepsin digestion and slab gel
      electrophoresis with capillary separations allows a relatively easy
      identification of in vivo occurring collagen fragments. Capillary electrophoresis
      can be done either in 25 mM phosphate buffer (pH 2.5) or in a 25 mM phosphate
      buffer (pH 4.5) made 0.1% with respect to sodium dodecyl sulfate (SDS). While in
      the first case peptides move to the cathode in a molecular mass dependent manner,
      in the second case they move towards anode (also in a molecular mass dependent
      manner). The profiles obtained by the two approaches resemble mirror images with
      low molecular mass peptides moving first in the acid background electrolyte while
      they move last in the presence of SDS. It is proposed that in the capillary
      electrophoretic separation at pH 2.5 the separation mechanism involves the
      interaction of the individual peptides with the capillary wall while in the
      second case (pH 4.5) the leading mechanism of separation involves the interaction
      of the analytes with the micellar phase. For micellar phase separation the system
      must be run at reversed polarity. Capillary electrophoretic separation in the pH
      2.5 buffer is considerably affected by the presence of SDS in the previous steps
      of peptide preparation. If the peptides are obtained from SDS slab gel
      electrophoresis, their movement in the capillary electrophoresis step is about
      three times faster that the movement of corresponding peptides which have not
      been complexed with SDS.

PMID- 9513293
TI  - Preparative gradient elution chromatography of chemotactic peptides.
AB  - Experimental and computational studies are carried out on the separation of a
      mixture of chemotactic peptides by reversed-phase gradient elution on commercial
      octadecyl silica supports with acetonitrile as the modulator. The solubility of
      this mixture is found to be a complex function not only of mobile phase
      composition, but also of the order in which the various constituents of the
      mobile phase are mixed together. In certain cases, the feeds seem to reach a
      metastable state in which they are fully soluble for several hours: this is
      exploited here for preparative separations. Separations are also carried out by
      stepwise and nonlinear isocratic elution, and the yields and productivities
      compared to those from gradient elution. Predictive simulations of all these
      separations are run using independently measured single component feed isotherms.
      Good agreement with experiment is found when multicomponent (nonlinear) feed
      interactions are accounted for, but not when the usual assumption of linear feed
      isotherms is made. Simultaneous concentration and separation of these feeds is
      easily achieved by gradient elution. Simulations indicate that the combination of
      the focusing power of the gradient with the multicomponent feed interactions is
      likely to give good separations even at high feed loadings.

PMID- 9513295
TI  - [Variant component analysis of bacterial count in milk. 2. Consequences for the
      preparation of microbiological inspection plans].
AB  - Results of the repeated testing of pasturized and raw milk to determine the
      bacterial count deviation in parallel samples were described in the first
      communication. Using the same data, the second communication demonstrates the
      influence of the observed bacterial count variation on the decision-making
      process of the simultaneously performed microbiological sampling plan. Analysis
      of the 3-class sampling plans under applied conditions showed that little
      attention was paid to the real variation of the criterion and in some plans, too
      much weight was placed on the possible outliers. Due to theoretical
      considerations, the difference between m and M in sampling plans with n = 5 and
      c(m) = 2 should at least amount to 1.85 times the standard deviation. This
      premise corresponds to the half of a tenth power in milk with homogenous
      bacterial population. It seems absolutely unwarranted to interrupt the
      examination of raw milk when the first random sample with n = 1 is lower than the
      GMP-limit. Examples show that in borderline cases where the bacterial counts are
      close to the cut-off value, the application of this strategy leads to the
      acceptance of numerous rejectable batches. Because of the few coliform counts in
      fresh, raw milk and especially in pasteurized milk, examination procedures with a
      detection limit of 1 cfu/ml are not advised and the quality assessment of a lot
      based on single random samples is not possible.

PMID- 9513294
TI  - Theory of the correlation between capillary and free-flow zone electrophoresis
      and its use for the conversion of analytical capillary separations to continuous
      free-flow preparative processes. Application to analysis and preparation of
      fragments of insulin.
AB  - A basic theoretical description of the correlation between capillary zone
      electrophoresis (CZE) and free-flow zone electrophoresis (FFZE) is presented. The
      theory of the correlation between CZE and FFZE results from the fact that both
      methods are based on the same separation principle, zone electrophoresis, and
      both are performed in the carrierless separation medium with the same composition
      of the background electrolyte. The equations describing the movement of the
      charged and noncharged particles in the d.c. electric field applied in the
      capillary and in the flow-through electrophoretic chamber are presented and used
      for the quantitative description of the correlation between CZE and FFZE. Based
      on the theory of the correlation between CZE and FFZE a procedure has been
      developed for conversion of analytical, microscale CZE separations into
      continuous preparative separation processes realized by FFZE. Practical
      application of the developed procedure is demonstrated by CZE analysis and FFZE
      preparation of an octapeptide fragment of human insulin.

PMID- 9513296
TI  - [Non carious neck lesions of the incisor teeth of domestic cattle].
AB  - Using archaeological and recent material it is shown that the origin of cervical
      lesions at the incisiva of cattle is dependent on the age of the animals. When
      colla dentes are laying free after recession of gingiva, the dentin is very
      sensitive against activity of proteolytic enzymes of chyme. Experiments show that
      these reactions occur especially in an alcaline pH range.

PMID- 9513297
TI  - [Effect of various factors on the suckling behavior of domestic rabbits].
AB  - An average number of 1.47 suckling events per 24 hours with a mean duration of
      203 seconds per suckling was shown in investigations with 156 does (253 litter,
      1.907 alive born pups) by continuous video recordings (infrared technique) over
      1.045 periods with 24 hours. Two or more suckling periods with maximum of six
      sucklings per 24 h were recorded in 40% of all days. Number and duration of
      suckling events and also percentage of days with > or = 2 sucklings/24 hours were
      significantly influenced by genotype of does, parity and keeping system
      (flatdeck, get-away-cage). ZIKA-hybrids had the highest percentage of days with
      several suckling periods (52.7). Suckling activity had shown a circadian rhythm
      and was significantly correlated with dawn (light-dark as an inducing factor for
      suckling). 25% of all suckling events took place in the hour after the lights
      were turned off.

PMID- 9513298
TI  - [Changes in hemostasis of dogs with acute lymphoblastic leukemia].
AB  - Twelve dogs suffering from acute lymphoblastic leukaemia were investigated
      concerning the following tests: platelet count, prothrombin time (PT, standard
      test, modified test), activated partial thromboplastin time (APTT), activity of
      the individual coagulation factors II, V, VII, X, VIII:C, IX, XI, XII,
      prekallikrein, and high-molecular weight kininogen, the activity of antithrombin
      III (AT III), protein C, plasminogen, and alpha 2-antiplasmin as well as
      concentration of fibrinogen, soluble fibrin and fibrin(ogen) degradation products
      (FDP). All patients showed a decreased platelet count due to suppression of
      megakaryopoesis by infiltration of the bone marrow with leukaemic cells. In
      addition, in most of the patients a moderate activity decrease of one or more
      individual coagulation factors has been found, especially regarding factor II
      (median, x0.50 = 51%, p = 0.0001), but also factors X (x0.50 = 71%, p = 0.0003)
      and XI (x0.50 = 68%, p = 0.0006). This was reflected by the APTT and the PT
      activity (modified test), which were prolonged or decreased, respectively, in the
      majority of the cases. Furthermore, the activity of AT III and of plasminogen was
      distinctly diminished (p < 0.001). Like the concentration of FDP, the plasma
      level of soluble fibrin was significantly higher than in normal dogs (p < 0.001).
      This indicates that besides thrombocytopenia disseminated intravascular
      coagulation occurs frequently in dogs with acute lymphoblastic leukaemia and is a
      main cause for the decreased activity of several plasmatic components of the
      haemostatic system. The lack of correlation between the concentration of soluble
      fibrin as an indicator of intravascular coagulation and the total blast cell
      count (rS = 0.011) shows the importance of other factors like degree of cell
      lysis as well as participation of organs such as the liver for generation of
      consumption coagulopathy in dogs with acute lymphoblastic leukaemia.

PMID- 9513299
TI  - [Radiotherapy in veterinary medicine (review)].
AB  - A review of the latest literature concerning the present level of radiation
      therapy in veterinary medicine is given. In a general section physico-technical
      as well as biological fundamentals are discussed. In the special part of the
      paper indications for a radiation therapy of dogs, cats and horses are stated. In
      this respect the basis for a decision is the TNM-classification into different
      clinical stages according to the directions of the WHO. Tumors of the
      hemolymphatic system are very responsive to radiation therapy. While epithelial
      tumors are sensitive, tumors arising from the mesenchymal tissues react less
      sensitive. Melanoma and osteosarcoma seem to be resistant to radiation therapy.
      Besides this, radiation therapy is often questioned by the tolerance of the
      normal tissue.

PMID- 9513300
TI  - Predictors of aspiration pneumonia: how important is dysphagia?
AB  - Aspiration pneumonia is a major cause of morbidity and mortality among the
      elderly who are hospitalized or in nursing homes. Multiple risk factors for
      pneumonia have been identified, but no study has effectively compared the
      relative risk of factors in several different categories, including dysphagia. In
      this prospective outcomes study, 189 elderly subjects were recruited from the
      outpatient clinics, inpatient acute care wards, and the nursing home care center
      at the VA Medical Center in Ann Arbor, Michigan. They were given a variety of
      assessments to determine oropharyngeal and esophageal swallowing and feeding
      status, functional status, medical status, and oral/dental status. The subjects
      were followed for up to 4 years for an outcome of verified aspiration pneumonia.
      Bivariate analyses identified several factors as significantly associated with
      pneumonia. Logistic regression analyses then identified the significant
      predictors of aspiration pneumonia. The best predictors, in one or more groups of
      subjects, were dependent for feeding, dependent for oral care, number of decayed
      teeth, tube feeding, more than one medical diagnosis, number of medications, and
      smoking. The role that each of the significant predictors might play was
      described in relation to the pathogenesis of aspiration pneumonia. Dysphagia was
      concluded to be an important risk for aspiration pneumonia, but generally not
      sufficient to cause pneumonia unless other risk factors are present as well. A
      dependency upon others for feeding emerged as the dominant risk factor, with an
      odds ratio of 19.98 in a logistic regression model that excluded tube-fed
      patients.

PMID- 9513301
TI  - A preliminary comparison of videofluoroscopy of swallow and pulse oximetry in the
      identification of aspiration in dysphagic patients.
AB  - Pulse oximetry has recently received attention in the dysphagia literature
      because of its possible contribution to the management of neurogenic dysphagia.
      The present study was devised to examine whether pulse oximetry could be
      exploited to determine episodes of aspiration in patients with known dysphagia of
      neurologic origin. To this end, pulse oximetry was undertaken in six patients
      undergoing videofluoroscopic study of swallow. Normal controls also underwent
      pulse oximetry during feeding. The results indicate that there is no clear-cut
      relationship between changes in arterial oxygenation and aspiration. However,
      some support is found for the association between altered arterial oxygenation
      and oral feeding in dysphagic individuals. Further research in both normals and
      compromised individuals is needed.

PMID- 9513302
TI  - Fiberoptic endoscopic evaluation of swallowing with sensory testing (FEESST) in
      healthy controls.
AB  - The purpose of this study was to introduce a new method of bedside assessment of
      both the motor and sensory components of swallowing called fiberoptic endoscopic
      evaluation of swallowing with sensory testing (FEESST). This approach combines
      the established bedside endoscopic swallowing evaluation with a more recently
      described technique that allows objective determination of laryngopharyngeal (LP)
      sensory discrimination thresholds by delivering air pulse stimuli to the mucosa
      innervated by the superior laryngeal nerve via a flexible endoscope. A
      prospective study was conducted of FEESST in 20 healthy control subjects, mean
      age of 34 +/- 11 years. LP sensory thresholds were defined as either normal (<
      4.0 mmHg air pulse pressure [APP]), moderate deficit (4.0-6.0 mmHg APP), or
      severe deficits (> 6.0 mmHg APP). Subsequent to LP sensory testing, food of
      varying consistencies, mixed with green food coloring, was given and attention
      was paid to spillage, laryngeal penetration, pharyngeal residue, aspiration, and
      reflux. Therapeutic maneuvers such as postural changes and airway protection
      techniques were performed on each subject to determine if the assessed swallowing
      parameters were affected by maneuvers. All patients completed the study; all had
      normal LP sensory discrimination thresholds (2.9 +/- 0.7 mmHg APP). There were no
      instances of spillage, laryngeal penetration, or aspiration. Two of 20 subjects
      had pharyngeal residue and 2 of 20 had reflux. Institution of therapeutic
      maneuvers resulted in a predictable change in the endoscopic view of the
      laryngopharyngeal anatomy. FEESST provides comprehensive, objective sensory and
      motor information about deglutition in the bedside setting and might have
      implications for the bedside diagnosis and management of patients with dysphagia.

PMID- 9513303
TI  - Laryngeal sensation: a touchy subject.

PMID- 9513304
TI  - Videofluorographic study of swallowing in Parkinson's disease.
AB  - We studied 16 patients with Parkinson's disease (PD) with dysphagia and 8 young
      and 7 elderly normal controls videofluorographically to evaluate the nature of
      swallowing disorders in PD patients. In 13 patients, abnormal findings in the
      oral phase were residue on the tongue or residue in the anterior and lateral
      sulci, repeated pumping tongue motion, uncontrolled bolus or premature loss of
      liquid, and piecemeal deglutition. Thirteen patients showed abnormal findings in
      the pharyngeal phase, including vallecular residue after swallow, residue in
      pyriform sinuses, and delayed onset of laryngeal elevation. Ten of these patients
      also showed abnormal findings in both the oral and pharyngeal phases. Aspiration
      was seen in 9 patients. The oral transit duration was significantly longer in the
      patients with and without aspiration than in the control subjects. The stage
      transition duration, pharyngeal transit duration, duration of the upper
      esophageal sphincter (UES) opening, and total swallow duration were significantly
      longer in the patients with and without aspiration than in the young controls,
      but were not longer than in the elderly controls. These durational changes in the
      pharyngeal phase of swallowing were similar to those in the elderly controls. The
      findings suggest that the disturbed motility in the oral phase of swallowing may
      be due to bradykinesia. Although PD patients with dysphagia evince a variety of
      swallowing abnormalities, the duration of pharyngeal swallowing may remain within
      the age-related range until the symptoms worsen.

PMID- 9513305
TI  - Functional imaging of the pharynx using electron beam tomography.
AB  - Due to long scan times it was impossible to make dynamic swallowing imaging using
      computer tomography (CT) of the third or fourth generation. This study evaluates
      whether electron beam tomography with scan times of 100 ms enables a more
      detailed dynamic imaging of swallowing disorders. Examination using electron beam
      tomography was done in three planes: (1) Passavant's cushion (n = 6), (2)
      thyrohyoid membrane (n = 9), and (3) upper esophageal sphincter (n = 5). The
      technique is discussed here in detail and documented with figures of the plane
      before swallowing as well as the intradeglutitive reachend plane. This study
      shows that electron beam tomography enables dynamic imaging of pharyngeal
      deglutition in transverse planes and can give useful additional information to
      the videofluorographic or kinematographic swallowing examination, which remain
      the gold standard in the functional evaluation of swallowing disorders.

PMID- 9513306
TI  - Proposed catheter standards for pharyngeal manofluorography (videomanometry)
AB  - With the recent introduction of commercially available pharyngeal
      manofluorography systems, catheter design should be standardized. Catheters of
      different designs can produce different data because of their design
      characteristics. A standard catheter design should make results between
      investigators comparable and facilitate acceptable normal values. The authors'
      combined laboratory experience with many catheter designs was reviewed and the
      literature consulted. For pharyngeal manofluorography, the proposed standard
      catheter should be 2 x 4 mm in diameter, ovoid, and 100 cm long. The catheter
      should be marked in centimeters with an anterior and posterior orientation. There
      should be a slightly malleable, 3- to 4-cm length without sensors beyond the most
      distal sensor. Solid state transducer sensors should be three or four in number
      and placed in the pharyngoesophageal segment, midhypopharynx, and tongue base
      (esophagus for fourth sensor). Sensor spacing should be 3 cm, except 2 cm between
      the midhypopharynx and tongue base. Unidirectional, in-line, posteriorly oriented
      sensors with the option of a single circumferential sensor in the cricopharyngeus
      are currently preferred over circumferential sensors because of their small
      diameter (patient comfort).

PMID- 9513307
TI  - First measurement standards, then catheter standards, for manofluorography.

PMID- 9513308
TI  - Radiation doses to patients during pharyngeal videofluoroscopy.
AB  - Pharyngeal videofluoroscopy (VTF) is a well-recognized technique for
      investigating and assessing swallowing disorders. There is, however, a paucity of
      data available regarding the radiation dose to patients during such procedures,
      but there is general concern that fluorographic imaging modalities are associated
      with significant radiation exposure. We have recorded the dose received by 23
      patients undergoing VTF in our department using a Dose-Area Product (DAP) Meter
      and have used the data to calculate the effective dose to the patients. The mean
      effective dose is 0.4 mSv (range 0.027-1.1) which compares favorably with the
      effective doses associated with other common radiological procedures. We
      therefore conclude that the radiation detriment associated with pharyngeal VTF is
      well within acceptable levels.

PMID- 9513309
TI  - [Unclear about prophylaxis against Rh-immunization. Much is missing from the
      guidelines of the National Board of Health and Welfare].

PMID- 9513310
TI  - [Reporting of medical news--belief, hope and knowledge].

PMID- 9513311
TI  - [An important progress in reconstructive surgery. Cultured blood vessels reduce
      the risk of thrombosis and rejection].

PMID- 9513312
TI  - [Privatization of health care strikes the weakest].

PMID- 9513314
TI  - [No to bribes but yes to--what?].

PMID- 9513313
TI  - [Diet information to pregnant women should be designed with great care].

PMID- 9513316
TI  - [Why not quality control of higher civil servants within the public sector?].

PMID- 9513315
TI  - [Reference methods and quality specifications of measurements in medicine].

PMID- 9513317
TI  - [Criticism against use of neuroleptics is still valid].

PMID- 9513318
TI  - [A distinct trend in Europe and USA. More and more physicians are positive when
      it comes to cannabis used for medical reasons].

PMID- 9513319
TI  - [Advances in the diagnosis of mycoses. New tests detect Candida infections].
AB  - New techniques for the detection of deep fungal infections are reviewed with a
      focus on Candida albicans, the species most frequently isolated. The introduction
      provides an outline of the similarities and differences between bacteria and
      fungi on one hand and animal cells on the other, which are important to bear in
      mind in the detection and treatment of deep fungal infections. In addition to
      cultures of biopsy material, blood, and mucous membranes (colonisation), serum
      tests for such fungal constituents as antigens or beta-glucan, the PCR technique
      for the detection of fungal DNA, and a test for the D-/L-arabinitol ratio in
      urine, are all valuable approaches. As yet, no single laboratory test is
      available that reliably detects disseminated candidosis. Rapid, sensitive, and
      specific methods for mycological diagnosis need to be developed to minimize the
      necessity of resorting to empirical therapy when deep mycosis is suspected.

PMID- 9513320
TI  - [No clinical rachitis in spite of incomplete AD-supplementation. Should the
      national recommendations be re-evaluated?].

PMID- 9513321
TI  - [Moral roots of prenatal diagnosis. Good care of the disabled is crucial for the
      ethical quality].

PMID- 9513322
TI  - [Physician's ability to communicate "cured" physical symptoms. "How to be more
      competent physicians].

PMID- 9513323
TI  - [Snake in the stomach a die-hard story].

PMID- 9513324
TI  - [Suppressive effects of ketamine on neuropathic pain].
AB  - We previously reported that ketamine analgesia in acute pain was produced by the
      activation of the monoaminergic descending inhibitory system. Recent studies have
      confirmed that the NMDA receptor antagonists attenuate the hyperalgesia in
      neuropathic pain. In this study, we investigated the suppressive effects of a
      clinically available NMDA antagonist, ketamine, and the mechanisms of its effects
      on neuropathic pain in rats with peripheral mononeuropathy. A unilateral chronic
      constriction injury (CCI) model was introduced by loose ligation of the sciatic
      nerve of the rats. The CCI rats showed hyperalgesia to thermal and mechanical
      pressure stimuli on the injured side of their hind paws. Intraperitoneal (IP)
      ketamine (25 or 50 mg.kg-1) and intrathecal (IT) ketamine (25-500 micrograms)
      reversed, dose-dependently, both thermal and mechanical hyperalgesia.
      Pretreatment with IT yohimbine (alpha-2 adrenergic antagonist) or IT methysergide
      (serotonergic antagonist) did not show the suppressive effects of IP ketamine (50
      mg.kg-1) on hyperalgesia. Concentrations of norepinephrine (NE) and serotonin
      (5HT) in the spinal dorsal horn were measured using high performance liquid
      chromatography. The CCI rats showed increased NE and 5HT concentrations on both
      ligated and unligated sides of spinal dorsal horn, compared with shamoperated
      rats. IP ketamine (50 mg.kg-1) in the CCI rats did not boost the spinal NE or 5HT
      levels. These results indicate that the anti-hyperalgesic effect of ketamine is
      derived from a direct action on the spinal cord, but not from the activation of
      monoaminergic descending inhibitory systems.

PMID- 9513325
TI  - [The effects of midazolam on the memory of pain].
AB  - The purpose of this study was to evaluate the effects of low dose midazolam (MZ)
      on memories of spinal puncture. The low doses of MZ were administered to 70
      patients (ASA 1-2), of whom 37 patients were premedicated with atropine sulfate
      0.5 mg and pethidine hydrochloride i.m. (group P), and 33 patients received no
      premedication (group N). Double blind randomized trials were conducted with the
      doses of MZ (0, 0.03, 0.06 mg.kg-1), and MZ was administered i.v. to the patients
      just prior to spinal puncture. Subjective evaluation of pain was performed with
      pain score (PS) on postoperative phase, and objective evaluation of pain was
      performed with the reaction of spinal puncture. Short term memory was impaired
      mainly after administration of MZ. However, subjective memory of pain almost
      disappeared, but objective evaluation was not so good. We conclude that MZ
      induces impairment to recall of pain. However, it might maintain the response to
      the pain.

PMID- 9513326
TI  - [Changes in aminopeptidase N located on neutrophils derived from patients with
      chronic pain].
AB  - It is known that aminopeptidase N (APN) and neutral endopeptidase (NEP) in the
      central nervous system (CNS) regulate opioid peptides, leading to pain
      modulation. To examine whether these enzymes located on human neutrophils (PMNs)
      play a role in several modalities of pain, we measured the activity of these
      enzymes located on PMNs derived from patients with chronic pain and compared this
      with that of healthy volunteers. APN activity in the group of patients with
      chronic pain was significantly increased compared with that in group of healthy
      volunteers (4.25 +/- 0.17, n = 36 vs 3.53 +/- 0.21, n = 24, nmol.min-1.10(6)
      cells, P > 0.05, mean +/- SE). But NEP activity showed no differences in two
      groups. These results suggest that APN located on PMNs from patients with chronic
      pain may act as an indicator of continuous painful condition and there may be a
      pain-modulating system in the blood.

PMID- 9513327
TI  - [Comparison of transarterial technique and paresthesia technique of axillary
      brachial plexus block].
AB  - Axillary brachial plexus blocks were established in 40 patients using
      transarterial technique (n = 20) or paresthesia technique (n = 20). Sensory and
      motor blockades of nerves supplying the upper extremity were compared at 10, 20
      and 30 minutes after the injection of local anesthetics (1.5% plain mepivacaine
      40 ml). Sensory blockades of the radial nerve and axillary nerve were
      significantly higher with transarterial technique than paresthesia technique. The
      incidence of analgesia of the radial nerve at 30 min was 100% with transarterial
      technique and 70% with paresthesia technique. Sensory blockades of the other
      nerves and motor blockades of all nerves did not show any significant differences
      between the two techniques. Proximal and distal spreads of the local anesthetic
      contrast medium mixture within the axillary neurovascular sheath were studied in
      20 patients. No statistically significant difference was observed in the spread
      of contrast agent between the two techniques. Transarterial technique is a
      recommendable method for hand surgery and especially indicated for the surgery of
      the area supplied by the radial nerve.

PMID- 9513328
TI  - [Relationship between cardiac output and PETco2 as well as Paco2 during high-dose
      fentanyl anesthesia].
AB  - We investigated the relationship between cardiac output and PETCO2 as well as
      blood PCO2 in 10 patients undergoing cardiac surgery of long duration under high
      dose fentanyl anesthesia. After anesthetic induction, the minute ventilation was
      kept constant at 10 ml.kg-1 x 10 cycles.min-1 and a pulmonary artery catheter was
      inserted. PETCO2, PaCO2 and cardiac index (CI) were measured simultaneously.
      PaCO2 was corrected for body temperature, and alveolar dead space-to-tidal volume
      ratio was calculated as VD/VTalv = (PaCO2-PETCO2)/PaCO2. After body, temperature
      became stabilized, the measurements were started and repeated every 10 to 20
      minutes during the prebypass period. One hundred and eight sets of data were
      taken from 10 patients. PETCO2 correlated positively with CI. Similarly, PaCO2
      correlated positively with CI, but VD/VTalv, did not correlate with CI. PETCO2
      correlated closely and positively with PaCO2, but it correlated negatively and
      only marginally with VD/VTalv. When examined in individual patients, PaCO2
      correlated positively with PETCO2 in all patients, while VD/VTalv correlated
      negatively with PETCO2 only in 3 patients. By multiple regression analysis,
      VD/VTalv change accounted for only 22.3 +/- 15.0% of PETCO2 change, while PACO2
      or PaCO2 change accounted for 77.6 +/- 15.0% of PETCO2 change. Decreased CI was
      associated with decreased CO2 delivery from the tissue to the lung (DCO2) and
      PaCO2 decreased with decreasing DCO2. Decreased CI was also associated with
      decreased oxygen uptake (VO2), and PaCO2 decreased with decreasing VO2. A
      decrease in CI resulted in an increase in VA/Q, and PaCO2 decreased when VA/Q
      increased. PETCO2 decreased when cardiac output decreased. A decrease in PACO2
      explained the decrease in PETCO2 better than an increase in VD/VT did. Decreased
      cardiac output might cause hypocapnia through decreased CO2 delivery to the lung,
      decreased CO2 production and/or increased ventilation-to-perfusion ratio.

PMID- 9513329
TI  - [Propofol and sevoflurane--a comparison of anesthesia for laryngomicrosurgery].
AB  - Laryngomicrosurgery has some special characteristics. It is under much stress
      such as intubation and direct laryngoscopy during a short operation time.
      Therefore both adequate anesthesia and quick recovery are needed. Thirty three
      ASA physical status I patients for laryngomicrosurgery were randomly assigned to
      receive either anesthesia with propofol and small dose of fentanyl (Group P) or
      anesthesia with thiopental and sevoflurane (Group S). Group P was induced with
      propofol 2-3 mg.kg-1 and fentanyl 0.1 mg and maintained with propofol 6 mg.kg-1.h
      1 (from 10 mg.kg-1.h-1 by 2 mg.kg-1.h-1 decrement in interval of 10 minutes). No
      intravenous analgesic was added. Group S was induced with thiopental 4 -5 mg.kg-1
      and maintained with sevoflurane 2-3%. We compared emergence time and the state of
      recovery 5 minutes after extubation and 5 minutes after entering the recovery
      room. There was no episode of inadequate anesthetic state in both groups. The
      emergence time was significantly shorter in Group P than in Group S. The state of
      recovery was much better in Group P compared with Group S in both 5 minutes after
      extubation and 5 minutes after entering the recovery room. Therefore, anesthesia
      with propofol and small dose of fentanyl at induction is more adequate compared
      with anesthesia with sevoflurane in laryngomicrosurgery.

PMID- 9513330
TI  - [Measurement of functional residual capacity by nitrogen washout during
      mechanical ventilation].
AB  - A medical gas analyzer AMIS 2000 SP, which is a mass spectrometer, incorporating
      a fractional residual capacity (FRC) measuring program based on a nitrogen
      washout method, has been introduced recently. The purpose of this study was to
      assess the reliability and the reproductivity of the FRC measuring system in a
      clinical situation. FRC was measured by this system connected to a ventilator
      (Bennet 7200ae). Our study examined; 1) the accuracy of the measurement using a
      syringe. 2) the difference in two consecutive measurements in the same subject
      during mechanical ventilation, and 3) the correlation between the measured and
      the predicted value calculated with Gorldman's formula in 18 subjects during
      ventilation. The first study has showed an excellent correlation (y = 0.953x +
      0.092, r = 0.996, P < 0.001) or y = 0.909x + 0.132 (r = 0.999, P < 0.001) with a
      tidal volume of 400 ml or 500 ml, respectively) between the measured value and
      the syringe capacity. Reproductivity was proved by the linear regression (y =
      0.977x + 0.024, r = 0.998, P < 0.001) between the two consecutive measurements. A
      good correlation was shown between the measured values and the predicted values
      (y = 0.656x - 0.415, r = 0.849, P < 0.0001). These results showed good
      reliability and reproductivity of our FRC measuring system. It is concluded that
      the FRC measurements using AMIS2000SP system can be used in clinical respiratory
      managements in ICU.

PMID- 9513331
TI  - [Placement of self-expanding metallic stents in the stenotic trachea and bronchus
      under the support of gas exchange by extracorporeal lung assist (ECLA)].
AB  - Three self-expanding metallic stents (MS) were placed in a patient with severe
      dyspnea due to tracheo-bronchial stenosis caused by a large metastatic malignant
      tumor. To ensure adequate gas exchange, we used ECLA during surgery. After ECLA
      was started with V-V bypass (blood flow 1.3 l.min-1, 100% O2 flow 10 l.min-1),
      the patient was administered droperidol and fentanyl, and orotracheally intubated
      with an endotracheal tube (7.0 mm ID) using a bronchofiberscope. Anesthesia was
      maintained with midazolam, but no neuromuscular blocking agent was used. The
      pulmonary ventilation was withheld 3 times during each period of 5-10 min for MS
      placement through the endotracheal tube. The patient was ventilated for a few min
      between each procedure. Values of arterial blood gas were maintained within
      physiological ranges throughout the surgery. ECLA was a useful means of ensuring
      adequate gas exchange in perioperative patients with difficult airway.

PMID- 9513332
TI  - [Preanesthetic assessment of a patient with giant negative T waves on ECG
      following subarachnoid hemorrhage].
AB  - Giant negative T waves on ECG are associated with intracranial hemorrhage such as
      subarachnoid hemorrhage, ischemic heart disease such as subendocardial
      infarction, myocardial disease and others. They embarrass us in anesthetic
      management of urgent neurosurgical patients because of the requirement of making
      differential diagnosis among these diseases accompanying the ECG abnormality. An
      80 year old woman undergoing radical clipping for cerebral artery aneurysm showed
      giant negative T waves on ECG. Although the ECG taken on admission to the
      hospital had been normal, huge giant negative T waves of 2 mV and QTc
      prolongation were detected on arrival in the operating room. Therefore, her
      cardiac function was evaluated by echocardiography to rule out subendocardial
      infarction. The echocardiogram revealed that wall motion of the left ventricle
      was mildly depressed, but her cardiac function was well maintained since the
      cardiac output was 4.1 l.min-1 and the ejection fraction was 59%. We thought that
      giant negative T waves were caused by subarachnoid hemorrhage and decided to
      perform anesthesia and surgery. Circulation during anesthesia and surgery was
      stable except a transient decrease in blood pressure due to massive hemorrhage
      during rupture of the aneurysm. We conclude that preanesthetic assessment of
      cardiac function by echocardiography is useful for anesthetic management of
      patients with giant negative T waves on ECG undergoing urgent radical operation
      for cerebral aneurysm.

PMID- 9513333
TI  - [Postoperative hypoxia and hyperfibrinolysis in patients after total knee
      replacement].
AB  - It was revealed that postoperative hypoxia had occurred frequently in patients
      after total knee replacement (TKR) in our preliminary study. Since we speculated
      that pulmonary embolism was the cause of the hypoxia, we investigated the
      relationship between PaO2 and D-dimer in patients after TKR and high tibial
      osteotomy (HTO). A total of 13 patients with the diagnosis of osteoarthritis were
      studied. Ten patients underwent TKR and three received HTO under subarachnoid
      block. Arterial oxygen tension and D-dimer were unchanged in patients who had
      undergone HTO. Even on the 5th postoperative day, five of the ten patients after
      TKR revealed a decrease in oxygen tension by more than 10% compared with the
      preoperative control (hypoxia group). In the other patients after TKR, a decrease
      of oxygen tension on the 5th postoperative day was under 10% (non-hypoxia group).
      There was a positive correlation between a decrease of PaO2 and a value of D
      dimer in all of the patients who had undergone TKR and HTO. Although no patient
      developed dyspnea clinically, one patient in hypoxia group was diagnosed as
      pulmonary embolism in the scintigram. It is likely that pulmonary embolism is the
      cause of postoperative hypoxia in patients after TKR.

PMID- 9513334
TI  - [HELLP syndrome in triplet pregnancy complicated by DIC and transient diabetes
      insipidus].
AB  - A 29-year-old woman with a triplet pregnancy received emergency caesarean section
      in the 33rd week of pregnancy. She lost 2 babies, one of whom was a fetal death
      and the other a neonatal death. Three weeks before delivery, she was admitted to
      hospital suffering from vomiting, diarrhea and polyuria. There were no laboratory
      abnormalities such as a slightly elevated levels of liver enzymes, nor any
      clinical symptoms of preeclampsia. At the end of the operation, disseminated
      intravascular coagulation (DIC) occurred and HELLP syndrome was diagnosed.
      However, the hemoglobin level was in the normal range at this point. On the 2nd
      postoperative day, hemolytic anemia developed in spite of the resolution of other
      problems. We suggested that the hemolysis, which may have been caused by a latent
      hemoconcentration and a membrane disorder of the red cells, was an osmotic
      hemolysis. This case was unique for the following reasons; 1) a lack of symptoms
      of hypertension, proteinuria and edema, 2) complications due to diabetes
      insipidus, 3) postpartum severe hemolysis following latent hemoconcentration, and
      4) slow progress of the condition after onset. Early detection of HELLP syndrome
      is difficult. It should be considered in the management of patients with
      unrecognizable hemoconcentration and nonspecific complications.

PMID- 9513335
TI  - [Perioperative management of two patients with severe dilated cardiomyopathy].
AB  - We report perioperative management of two patients with severe dilated
      cardiomyopathy belonging to the group IV of classification of Inoh (ejection
      fraction 18% and 30%). In the preoperative period, they developed severe
      congestive heart failure. Dopamine, dobutamine, and furosemide were given to
      improve cardiac function. Anesthesia was performed safely under continuous
      cardiac output and mixed venous saturation monitoring. We consider that
      preoperative evaluation and management are very important to prevent
      intraoperative and postoperative complications in patients with severe dilated
      cardiomyopathy.

PMID- 9513336
TI  - [Anesthetic management of a patient with antiphospholipid syndrome].
AB  - A 46-year-old woman with antiphospholipid syndrome (APS) underwent an emergent
      laparotomy. The symptoms and signs of APS are reported to be thrombosis, habitual
      abortion, thrombocytopenia and biological false positive (BFP) for syphilis'
      tests. Clinical symptoms are based on hypercoagulation of blood, while
      prothrombin time (PT) activity and activated partial thromboplastin time (APTT)
      are prolonged. Although we have selected general endotracheal anesthesia without
      epidural catheterization, we recommend that the regional analgesia is suitable
      for those APS patients with abnormality of coagulation. If PT and APTT differ
      from clinical symptoms, we have to think about APS and manage the patients
      carefully as APS.

PMID- 9513337
TI  - [Mild hypothermia anesthesia for carotid microendoarterectomy in a patient with
      ischemic heart disease].
AB  - A 69 year-old male with ischemic heart disease indicated for coronary artery
      bypass grafting was scheduled for carotid microendoarterectomy. We induced mild
      hypothermia technique with vasodilation and surface cooling by convecting warming
      device. We examined hemodynamics by pulmonary artery catheter. Anesthesia was
      induced with thiamylal, fentanyl, midazolam and isoflurane in nitrous oxide and
      oxygen. Following administration of vecuronium, trachea was intubated. Pulmonary
      artery catheter was inserted from the femoral vein. Dopamine, dobutamine 3-5
      micrograms.kg-1.min-1 and PGE1 5-10 ng.kg-1.min-1 were continuously administered
      to keep peripheral blood circulation and cardiac output (CO). Systemic vascular
      resistance decreased from 1800 to 591 dyne.s.cm-5 and CO increased from 2.8 to
      6.9 l.min-1. The occlusion of blood flow of the right carotid artery for 40 min
      at 34.5 degrees C of rectal temperature did not cause any neurological deficits.
      No other complications such as arrhythmia, myocardial ischemia and bleeding
      tendency were observed. Keeping peripheral blood circulation and uniform cooling
      and warming are important in inducing mild hypothermia safely in a patient with
      ischemic heart disease.

PMID- 9513338
TI  - [Intraoperative anaphylaxis caused by latex surgical gloves].
AB  - A 17-year-old male encountered anaphylaxis caused by latex surgical gloves during
      emergency surgery under general anesthesia. He had undergone multiple surgical
      procedures, bladder catheterization and was suffering from atopic dermatitis. The
      patient developed bronchospasm and circulatory collapse 20 minutes after the
      start of surgery. Administration of dopamine, aminophylline and
      methylprednisolone helped to normalize airway pressure and blood pressure. Latex
      allergy occurs in persons considered at high risk including patient with spina
      bifida, urogenital abnormalities, atopic dermatitis, health care workers and
      rubber industry workers. These persons may develop hypersensitivity to latex
      products. If patients who are suspected to be latex allergy undergo surgical
      procedures, anesthesiologist should check past history and sensitivity to rubber
      in detail. In patients known to be allergic to latex, we must avoid latex
      products, such as surgical gloves, or anesthetic and surgical equipments.

PMID- 9513339
TI  - [Multiple cerebral infarction during anesthesia in a patient with
      hypergammaglobulinemia].
AB  - We experienced anesthetic management of two patients with hypergammaglobulinemia
      undergoing thoracoscopic lung biopsy, one of whom suffered from multiple cerebral
      infarction during anesthesia. Pathogenesis of this serious complication could not
      be elucidated. However, decrease in cerebral regional circulation caused by
      increase in blood viscosity would be most probable. We should preoperatively
      carry out measurement of blood viscosity and brain CT scan, and consider plasma
      exchange in patient with hypergammaglobulinemia, in whom symptoms and signs of
      hyperviscosity syndrome do not exist.

PMID- 9513340
TI  - [Anesthetic management of a patient with dilated cardiomyopathy using olprinone].
AB  - A 51-year-old man with dilated cardiomyopathy, who had been treated with
      medication for five years, was scheduled for abdomioperineal resection of the
      rectum. Preoperative echocardiography demonstrated left ventricular dilation and
      hypertrophy, with an ejection fraction of 0.34. Anesthesia was induced with
      ketamine 40 mg and fentanyl 0.5 mg intravenously. Endotracheal intubation was
      facilitated by administration of vecuronium 10 mg. Anesthesia was maintained with
      nitrous oxide-oxygen-sevoflurane and fentanyl. In order to regulate myocardial
      contractility and after-load, use of a phosphodiesterase III inhibitor was
      considered, although phosphodiesterase III inhibitors are known to induce
      arrhythmias, which should be avoided in dilated cardiomyopathy patients. We chose
      olprinone, because its inotropic action is not associated with arrhythmogenecity.
      Before infusing olprinone, cardiac output was 4.5 l.min-1 and systemic vascular
      resistance was 1306 dynes.sec.cm-5. When olprinone was continuously infused for
      one hour, cardiac output increased to 5.2 l.min-1 and systemic vascular
      resistance decreased to 958 dynes.sec.cm-5. Some premature ventricular
      contractions occurred, but they were easily controlled by administration of 50 mg
      lidocaine. These clinical data demonstrate that olprinone enhanced myocardial
      contractility, and decreased after-load and arrhythmogenecity in a dilated
      cardiomyopathy patients. In conclusion, olprinone is useful in the perioperative
      cardiovascular management of surgical patients with dilated cardiomyopathy.

PMID- 9513341
TI  - [A case of ABO blood group incompatibility treated by exchange transfusion].
AB  - A patient with ABO blood group incompatibility who was treated by exchange
      transfusion is reported. A 63-year-old woman with blood group B type Rh (+) was
      accidentally transfused approximately 120 ml of A type Rh (+) packed red cells.
      She developed shock state, complaining chilliness, trepidation, nausea and
      vomiting just after the atypical blood transfusion. Fortunately, we could save
      her life without any complication by doing exchange transfusion in addition to
      anti-shock therapy and anticoagulant therapy preventing disseminated
      intravascular coagulation. The exchange transfusion was performed while
      monitoring central venous pressure. The total withdrawn blood reached 4300 ml,
      and 18 units of B type Rh (+) packed red cells, 10 units of AB type Rh (+) fresh
      frozen plasmas, 1250 ml of plasma protein fractions and 1750 ml of plasma
      expanders were infused with crystalloid fluid therapy. Although the amount of
      atypical blood transfusion to her was relatively small, it is considered that the
      exchange blood transfusion which seems to be only the fundamental therapy against
      atypical blood transfusion, took effect in saving her life without any
      complication.

PMID- 9513342
TI  - [The majority of emergency calls are erroneous].
AB  - An emergency call system has been used to summon specialists for cardiopulmonary
      resuscitation in Kumamoto University Hospital since 1986. Many improvements have
      been made to the system since it was established. We performed a prospective
      evaluation of calls made during the period from April 1, 1996 to March 31, 1997.
      There were a total of 36 calls, but only two of them were judged to be true
      emergencies. While at first we considered the number of calls reflected a growing
      awareness of the cardiopulmonary resuscitation team in the hospital, the large
      number of erroneous calls (94%) indicated other factors needed to be considered.
      Further investigation revealed the existence of a special, and little-known,
      telecommunication system connecting various administrative offices of the
      Japanese Government. Some of the phone numbers in this system are similar to the
      emergency call number. Thus many of the emergency calls were probably caused by
      administrative officers who misdialed. We are proposing to change this emergency
      call number.

PMID- 9513343
TI  - Leprosy Control Programme in Kalay Zone Sagaing Division, Union of Myanmar.

PMID- 9513344
TI  - [Towards new strategies to combat mycobacterial diseases].
AB  - Infectious diseases account for more than 30% of deaths throughout the world, and
      we are increasingly faced with new and reemerging disease challenges. Infections
      caused by mycobacteria are the leading cause of death from infectious diseases
      around the world. Leprosy/Hansen's disease, caused by Mycobacterium leprae,
      primarily involves the peripheral nervous system and skin. Tuberculosis remains
      an important global health problem with approximately 1.9 billion people
      presently infected with M. tuberculosis. Infections with nontuberculous
      mycobacteria such as M. avium complex (MAC) constitute an important health
      problem, because most strains of MAC are resistant to antituberculous drugs.
      Mycobacteria are intracellular microbial pathogens. The infect macrophages cause
      chronic inflammation, such as granulomatous inflammation, and progressive
      scarring. Host defense against mycobacterial infection is controlled
      predominantly by the macrophage-cytokine-type 1 helper T (Th1) cell axis
      resulting in the expression of cell-mediated immunity. Development of cell
      mediated, Th1(1) protective immunity to mycobacteria is considered a two-edged
      response, contributing to both clearance of infecting agents and tissue damage.
      In the second half of the 20th century, the conceptual approach to the management
      of established infectious diseases is antimicrobial chemotherapy. However, the
      successful implementation of antimicrobial chemotherapy is becoming increasingly
      difficult because of (1) an epidemic of immunocompromised patients, for whom
      antimicrobial therapy is less effective; (2) the emergence of new pathogens and
      the reemergence of old pathogens; and (3) widespread drug resistance.
      Antiinfective immunotherapy will be a new control strategy for mycobacterial
      diseases. It is also conceivable that therapeutic interventions to enhance the
      host immunity will be as effective as and possibly synergistic with antimicrobial
      drugs. We believe that the immune-based strategies will contribute to elimination
      of mycobacterial diseases.

PMID- 9513345
TI  - [High prevalence of leprosy in the Federated States of Micronesia and special
      project for the elimination].
AB  - Leprosy in Federated States of Micronesia is still endemic with incidence rate
      221/100,000 and prevalence 33/10,000 in 1996. The disease was introduced by the
      patients from Nauru. Epidemic of the disease was observed in Pingelap during the
      1960's and Kpingamarangi since 1966. Special project for the elimination of the
      disease by the chemoprophylaxis was launched in 1996. The preventive therapy is
      consist of one dose of an association of 3 antibiotics (rifampicin, ofloxacine
      and minocyclin) for adults and rifampicin alone for children. The project is
      completed for two years and followed by evaluation for 6 years. It is expected to
      reach the elimination level before year 2000.

PMID- 9513346
TI  - Regenerative changes in median nerve defects using various rabbit skeletal
      muscles.
AB  - We examined the morphological changes of median nerve regeneration which situated
      to pass through degenerative latissimus dorsi and brachial triceps muscles in
      rabbits. Morphological observation was performed at 7, 14, 28, 45, 60 and 180
      days after the creation of defect of the bilateral median nerves. Regenerative
      nerve fibers were observed in the residual tubes of left degenerative muscle
      bridges. In this respect the regenerative effect of the latissimus dorsi was
      better than that of the brachial triceps. These results suggest that regular and
      longer muscle fibers as those of latissimus dorsi may contribute to the effective
      regeneration of nerve.

PMID- 9513347
TI  - [On the lesions caused by a leproma-derived and cultivated Mycobacterium HI-75
      produced in ddY mice. With special reference to a factor influencing the lesions
      and the differences from those by BCG].
AB  - Not only in the experimental leprosy, primary aim to make every experimental
      model crucial for the medical research has been the simulation of the aspect of
      disease encountered in human case by the simplest possible way. The present study
      was conducted to do so making some variations in addition to the experimental
      lepromata, produced in nude mice by Sasaki et al. and by Hamit, utilizing a
      leproma-derived and cultivated Mycobacterium HI-75 (HI-75). In this study HI-75,
      Mycobacterium bovip BCG (BCG) and female SPF ddY(ddY) were utilized to make
      experimental models. In addition to these combinations, the effect of the
      immunization of beta-glucuronidase binding protein (BGBP) to the lesion was also
      examined. The BGBP extracted from pisum sativum and utilized in this study shows
      cross-immunoreactivity with those of HI-75 and M. leprae. As the results, the
      lesions caused by HI-75 and BCG were somewhat resembling though HI-75 caused a
      little more extensive lesions especially in lymphocytic and monocytic
      infiltration. Also HI-75 caused distinct nerve lesions(NL) in which the bacilli
      were often encountered in the endoneurium but not in those by BCG. Contrarily in
      mice immunized with BGBP, the lesions were only a little milder and the affected
      tissue was a little fibrosed. However, in NL the solid form HI-75 were more often
      observed in the endoneurium. The results indicated that the effect of BGBP
      immunization on the HI-75 induced lesion was not very clear by the present study
      alone, however, the proposed models itself should be and will become very useful,
      for experimental leprology with only slight modifications.

PMID- 9513348
TI  - A genomic study on the cultivable and nerve invading Mycobacterium HI-75 after
      the recovery 3 months of the inoculation to nude mice.
AB  - The sequence of the polymerase chain reaction (PCR) product of 16S ribosomal RNA
      (16S rRNA) of the leproma-derived and cultivable Mycobacterium HI-75 (M. HI-75)
      which was obtained from the infected regions of inoculated mice, was examined and
      compared with that of the cultured bacteria by the direct sequencing techniques.
      The sequence was completely consistent with the cultured bacilli in the
      comparable 837 bases of 16S rRNA. The mycobacterium examined in this study was
      originally isolated as M. leprae (ML) by Skinsnes, et al. in 1975 from leproma of
      a lepromatous type Hansen's disease patient and therefore named as Mycobacterium
      leprae HI-75 by them, and was maintained from 1984 using either Ogawa's or
      Sauton's media in the beginning and Ogawa's medium enriched with glucronic acid
      and N-acetyl-D-glucosamine recently. Sasaki and Hamit reported the nerve invasion
      and the growth of the inoculated bacilli either to the nude mice or the I131
      treated immunocompromised Swiss mice. We previously reported that cultured HI-75
      was most similar to M. scrofulaceum by the direct sequencing of the gene of 16S
      rRNA. The 16S rRNA obtained from the mouse tissue in the present study indicated
      that M. HI-75 would be a variant of M. scrofulaceum possessing an ability to
      invade into peripheral nerve. The results suggest that the HI-75 strain claims a
      nature as a pathogen to develop a leproma-like lesion.

PMID- 9513349
TI  - Pathological investigation of armadillos infected with Mycobacterium leprae.
AB  - An infection experiment with M. leprae was carried out using 20 nine-banded
      armadillos. As a result, the development of leprous lesions and a marked
      multiplication of AFB were confirmed in a high rate of 13 out of 15 cases (86.8%)
      in the inoculated groups. These changes were found to be progressing at post
      mortem of one case even with the shortest life period for 7.5 months and were
      very serious in one case with the longest life period for 33 months, suggesting
      the continuation of symptoms, though it is an expression neglecting the
      individual difference in susceptibility to leprosy. Among infected viscera with
      AFB, the most conspicuous lesions were found in the liver and spleen. The
      developed lesions were found in the lung, stomach and kidney which had been never
      seen in HD in human cases, and so, which may characterize armadillos' leprosy.
      The change in the peripheral nerve was not so severe when compared with that in
      HD in human cases. This difference will remain as a future pathological problem
      to be solved.

PMID- 9513350
TI  - Hypogonadal osteoporosis in elderly male patients with lepromatous leprosy.
AB  - Geriatric diseases have become significant problems in Japanese leprosariums. In
      particular, male osteoporosis seems to be more frequent in elderly leprosy
      patients than in non-leprosy elders. In 1987 we measured the cortical thickness
      of the 2nd metacarpal bone (MCI: metacarpal index) in 499 leprosy patients who
      were under medical treatment for osteoporosis. Of these patients, 139 were female
      patients with lepromatous leprosy (FL), 58 were female patients with tuberculoid
      leprosy (FT), 238 were male patients with lepromatous leprosy (ML) and the
      remaining 64 were male patients with tuberculoid leprosy (MT). The results were
      that the MCI of 238 ML was lower than 139 FL in the 4th, 5th 6th, and 7th decade
      of life. Furthermore the decreasing ratio of MCI peaked in the 4th decade was
      70.6% between the ages of the 8th decade in ML. We conclude that this is a
      manifestation of leprosy-specific osteoporosis, which is associated with
      testicular dysfunction in elderly male patients with lepromatous leprosy.

PMID- 9513351
TI  - [Uveitis and systemic diseases: a diagnosis of ocular sarcoidosis].

PMID- 9513353
TI  - [The cytotoxic effect of topical mitomycin C on the ciliary body in rabbits].
AB  - We evaluated the cytotoxic effects of mitomycin C (MMC) in rabbit eyes. A sponge
      soaked with MMC was placed on the bared sclera after conjunctival incision. We
      used four concentrations of MMC in distilled water: 0%, 0.04%, 0.1%, and 0.4%.
      MMC was applied to one eye only, with the fellow eye serving as control. The eyes
      were studied for intraocular pressure (IOP) and by fluorophotometry at 3, 7, 14,
      and 28 days of treatment. Eyes treated with 0.04% and 0.4% MMC were studied
      histologically at 3 and 28 days. All the MMC-treated eyes showed no significant
      changes regarding IOP (56 eyes) or fluorophotometric features (28 eyes) regarding
      aqueous humor dynamics and blood-aqueous barrier. Pathologic changes of the
      ciliary epithelium, including intracellular vacuoles and swelling of
      mitochondria, were more pronounced in eyes treated with 0.4% MMC than those
      treated with 0.04%. These changes were more manifest in areas inner to the site
      of application than in the opposite area. Topical application of 0.04% MMC thus
      showed no evident toxic effects on the function of the ciliary body and other
      pathological changes were minor.

PMID- 9513352
TI  - [The effect of matrix metalloproteinase inhibitor on pseudomonal proteinases].
AB  - We examined the effect of CS-610, a newly developed matrix metalloproteinase
      (MMP) inhibitor, on pseudomonal proteinase in vitro. Alkaline proteinase (1143
      4977 unit/ml Type I collagenase equivalent) and elastase (13.6-22.6 unit/ml Type
      I collagenase equivalent) were obtained from strains of P. aeruginosa of IID
      1117, IID-1030 and IID-1130. Zymographic analysis of cultured broth of P.
      aeruginosa demonstrated that CS-610 inhibited alkaline proteinase with an IC50
      (50% inhibition concentration) of 1.06-29.0 (x 10(-8)M) and elastase with an IC50
      of 1.0-33.3 (x 10(-8)M). CS-610 is a potent inhibitor of pseudomonal proteinases.

PMID- 9513354
TI  - [Critical time for developmental eye abnormalities induced by retinoic acid in
      mouse fetuses].
AB  - To identify the critical time for developmental eye abnormalities, pregnant C 57
      BL/6 NJcl mice were injected intraperitoneally once with 12.5 mg/kg of retinoic
      acid on days 7 (day-7 group), 8 (day-8 group), 9 (day-9 group), 10 (day-10
      group), and 11 (day-11 group) of pregnancy. Each group consisted of 5 pregnant
      mice. The fetuses were observed grossly on day 18 of gestation, and the eyes were
      examined histologically in serial sections. Various gross malformations such as
      microphthalmos, cleft lip and palate, and central nervous system anomalies were
      observed in the day-7 group. However, microphthalmos was the only gross
      malformation found in the day-8 group, and there were no gross malformations in
      the other 3 groups. The histological examination indicated that the critical time
      for anophthalmos was day 7 of gestation or earlier because of its appearance in
      the day-7 group alone. The critical time for microphthalmos, faulty closure of
      the embryonic fissure, aphakia, and faulty separation of the lens vesicle was day
      8 of gestation or earlier considering their occurrence in both day 7 and day 8
      groups, and the time for goniodysgenesis was day 9 of gestation or earlier
      because of its appearance in the day 7, day 8, and day 9 groups.

PMID- 9513355
TI  - [The mechanism of corneal epithelial disorder induced by prostaglandin F2 alpha
      isopropyl unoprostone].
AB  - Deleterious effects of isopropyl unoprostone (PG-F2 alpha) on the ocular surface
      were evaluated using the in vivo barrier function assay of corneal epithelial
      cells and the proliferation assay of human corneal epithelial cells in vitro. The
      barrier function of corneal epithelial cells in vivo was not impaired by
      treatment with PGF2 alpha, but it was significantly suppressed by timolol. The
      result of cell proliferation assay of human corneal cells showed that the 0.12%
      PGF2 alpha ophthalmic solution caused greater suppression of cell proliferation
      and acuter cell toxicity than 0.5% timolol ophthalmic solution. Further study
      showed that not the vehicle but the PGF2 alpha itself was responsible for these
      deleterious effects. We conclude that the 0.12% PGF2 alpha ophthalmic solution
      affects cell migration and proliferation but not the barrier effects of the
      ocular surface. These results suggest that the corneal epithelial defect of
      glaucoma patients may be caused by these two independent mechanisms, namely
      suppression of cell proliferation by PGF2 alpha and the destruction of the
      barrier function of the ocular surface by timolol.

PMID- 9513357
TI  - [Distribution of retinal sensitivity with blue on yellow perimetry in ocular
      hypertension].
AB  - We evaluated the visual field pattern with Blue-on-Yellow perimetry in 22 eyes of
      22 persons with ocular hypertension. Another series of 20 normal eyes served as
      controls. All the subjects underwent central field perimetry with a Humphrey
      automated perimeter (Model 640) using White-on-White targets. Blue-on-Yellow
      perimetry was performed within one week later. Both groups showed no difference
      in White-on-White perimetry, but the ocular hypertensive group showed a diffuse
      reduction in central sensitivity to Blue-on-Yellow perimetry by an average of 2.5
      dB compared with the controls. These findings show the possibility that ocular
      hypertension causes fragility of the blue-yellow transmission system including
      the blue cones.

PMID- 9513356
TI  - [Clinical manifestations and diagnosis of patients with sarcoidosis].
AB  - We reviewed the records of new patients with uveitis who visited the Hokkaido
      University Hospital between 1991 and 1994. For the diagnosis of sarcoidosis, we
      used the criteria revised by the Diffuse Pulmonary Disease Research Committee of
      Japan in 1989. The total number of patients was 374, and 61 cases were diagnosed
      as sarcoidosis. Of 61 patients with sarcoidosis, 58 cases were diagnosed
      histologically. Transbronchial lung biopsy was the basis for 70% of the
      histological diagnosis. After the revision of the criteria of sarcoidosis, the
      percentage of histological diagnosis increased. The Diffuse Pulmonary Disease
      Research Committee of Japan also proposed guidelines for the diagnosis of ocular
      sarcoidosis in 1990. We applied these guidelines to our uveitis patients. Most of
      the patients (77.1%) with sarcoidosis were included in the group of probable
      sarcoidosis, but 20% of patients with uveitis who were not diagnosed as having
      sarcoidosis were also included in this group. These guidelines are not yet
      adequate.

PMID- 9513358
TI  - [Cone sensitivity measurements in diabetic retinopathy].
AB  - We made cone sensitivity measurements and hue discrimination measurements in 58
      eyes of 34 diabetic patients with and without diabetic retinopathy including
      preproliferative retinopathy. The same measurements were performed in 8 eyes of 8
      subjects to compare them. In this study, we were able to make the measurements in
      a short time and comfortably for the patients because we only needed to measure
      peak sensitivities of spectral sensitivity curves in three cones. There was
      significant correlation between short wave length sensitive-cone pathway
      sensitivity and retinopathy levels determined by fluorescein angiography. The
      cone sensitivity measurements that we used in this study were simple and
      sensitive. Our results suggested that the measurements were useful for detection
      of visual functional disturbances, determination of retinopathy levels, and
      prognosis.

PMID- 9513359
TI  - [The present status of ophthalmological management for diabetics].
AB  - A questionnaire regarding management of patients with diabetes was mailed to 315
      ophthalmologists. The status of ophthalmological management at the hospitals and
      clinics was investigated. The return rate of questionnaires was 73%. The problems
      at the clinics were 1. many cases have ophthalmological symptoms at the first
      ophthalmological examination (longer time from the onset of diabetes to the first
      ophthalmological examination), 2. appropriate cooperation between ophthalmology
      and internal medicine is lacking, 3. the collection of information on blood
      glucose control level is difficult, and 4. there is not enough consultation by
      appointment. The common problems to both hospitals and clinics were 1.
      satisfactory measures are not taken regarding dropout ophthalmology patients, and
      2. a system of patient education does not exist. There is a pressing need for
      comprehensive measures to be taken by medical association leaders and medical
      administrators to settle these problems.

PMID- 9513360
TI  - [The effect of carbon dioxide on intraorbital hemodynamics in glaucoma determined
      by color Doppler imaging].
AB  - We developed a new system to safely supply carbon dioxide (CO2) to man to
      investigate the effect of the gas vasodilator on orbital blood flow in open angle
      glaucoma (OAG) patients. Using the system, we determined orbital hemodynamics in
      OAG by color Doppler imaging (CDI) at baseline conditions and during CO2
      supplementation sufficient to increase end-tidal CO2% by 10%. Seven OAG patients
      (mean age, 60.9 +/- 16.4 years; normal-tension glaucoma/primary open-angle
      glaucoma = 5/2) were included in the study. CDI was performed to measure
      resistance index (RI), and peak-systolic and end-diastolic blood flow velocities
      (PSV & EDV) of the ophthalmic artery (OA) and the central retinal artery (CRA).
      Systemic conditions including oxygen saturation and blood pressure were monitored
      throughout the period of the CO2 inhalation. CO2 significantly increased PSV and
      EDV in the CRA (p = 0.0273, p = 0.0094, respectively; Wilcoxon signed-rank test),
      but not in the OA. Other parameters were not altered. The results suggest that
      CO2 inhalation increases blood flow velocities in distal arteries in OAG patients
      without affecting proximal vessels. The new system enables us to supply CO2 in a
      safe and controlled manner in glaucoma patients and to modify orbital
      hemodynamics.

PMID- 9513361
TI  - [Orbital and stomach metastasis from invasive lobular breast carcinoma].
AB  - Orbital or ocular metastatic tumors may originate from breast cancer. Few studies
      have been made regarding their histopathological classification. A 71-year-old
      female noted a tumor in the right orbital region. She had had bilateral breast
      cancer 2 years before and gastric cancer 5 months before. Histopathology had
      shown stage II invasive ductal cancer (scirrhus) in the right breast and stage
      III invasive lobular cancer in the left. Signet-ring cells were present in the
      breast and gastric cancers. Biopsy of the right lower eyelid showed poorly
      differentiated adenocarcinoma with signet-ring cells. Indian file pattern, which
      is specific for invasive lobular cancer, was also present, suggesting that the
      orbital tumor had metastatized from the left breast cancer. Genetic analysis of
      the gastric cancer using polymerase chain reaction showed a mutation at exon 8 of
      the p53 tumor suppressor gene, indicating the cancer to be metastatic. These
      results led to the conclusion that invasive lobular cancer of the left breast was
      the primary lesion for the gastric and orbital metastases. This case also
      illustrates that signet-ring cells, which are usually seen in gastric cancer, may
      be present in invasive lobular breast cancer and in orbital metastasis.

PMID- 9513362
TI  - [Stress and neuropeptides].

PMID- 9513363
TI  - Clinicopathological studies on association of gallbladder carcinoma and
      pancreaticobiliary maljunction.
AB  - During the past 17 years, 1,722 of 4,832 consecutive patients investigated with
      endoscopic retrograde cholangiopancreatography (ERCP) were assessed by the
      radiological criteria of the Japanese Study Group of Pancreaticobiliary
      Maljunction (PBM). Out of these 1,722 patients, PBM was found in a total of 52,
      representing 3.0%, of which gallbladder carcinoma was associated with 14. These
      14 with gallbladder carcinoma consisted of 10 (62.5%) of the 16 with PBM without
      association of congenital bile duct dilatation (CBDD) and 4 (11.1%) of the 36 PBM
      with CBDD. The relationship between PBM and gallbladder carcinoma was closely
      examined; PBM was noted in 14 (32.6%) of a total of 43 patients with gallbladder
      carcinoma compared to 38 (2.3%) among the 1,679 patients with various diseases
      excluding gallbladder carcinoma. Similarly, it was revealed that gallbladder
      carcinoma was predominantly noted in the 14 (26.5%) of the 52 patients with PBM
      in contrast to an incidence of 1.7% (29) among the 1,670 patients without PBM. As
      we studied the characteristic clinical features of the 14 gallbladder carcinoma
      patients with PBM when compared with 29 of those without PBM, the following was
      disclosed: on average, the patients with PBM were 10 years younger (49.4 vs 61.4
      years in mean age); there was a preponderance of women (0/14 vs 12/17, male
      female ratio); there existed a significantly lower incidence of associated
      gallstone disease (7.1% vs 72.4%). These figures were shown to be statistically
      significant. We concluded that the results prove a link between the crucial
      features of gallbladder carcinoma and PBM, and also suggest the promotive role of
      PBM in carcinogenesis of the gallbladder.

PMID- 9513364
TI  - [The change of localization on cytokeratin of uterine cervix and the relationship
      to the pattern of invasion in cervical cancer].
AB  - An immunohistochemical study of 63 cases of uterine cervical cancer was
      undertaken. It was confirmed that the biological character of the cancer cells
      derived from the reserve cells changed over the course of invasion. Squamous cell
      carcinoma had positive keratin antibodies such as CK 10/13 (DE-K 13), CK 14 (NCL
      LL 002) and CK 7 (OV-TL 12/30). In invasive squamous cell carcinoma, CK 14
      positive cells were piled up and tended to be stained positive by PCNA and
      laminin. There were two types of staining, one of which revealed CK 14 strongly
      positive, and the other weakly positive. The first type differed from the second
      in depth and localization. The cells on the margin of a cluster of cancer cells
      were stained positive with CK 14 as in normal basal cells. The results obtained
      suggested: 1) squamous cell carcinoma has not only the character of normal
      squamous cells, but also that of the cells derived from the cervical glands. 2)
      cancer cells may develop in accordance with the character of basal cells, and the
      patterns of invasion change according to the character of basal cells in cancer
      tissue.

PMID- 9513365
TI  - [Electroencephalography and prognosis in stroke patients].
AB  - Electroencephalography (EEG) and its relationship to prognosis were studied in
      105 patients with cerebrovascular disease in the acute to subacute stages. Twenty
      cases had normal EEG, and most of them recovered well. Fifty-five cases had
      mildly to moderately abnormal EEG with focal asymmetric or slow waves in the
      unilateral hemisphere. Among them, 41 cases (75%) recovered to the extent of
      being capable of independent walking, 38 cases (69%) recovered sufficiently to
      engage in independent activities of daily livings (ADL) and 42 cases (76%)
      returned home. On the other hand 30 cases who had severely abnormal EEG with
      diffuse slow waves in the unilateral or bilateral hemispheres showed a poor
      prognosis. Among them, 18 cases (60%) were confined to bed, 20 cases (69%)
      remained in totally dependent ADL, and 4 cases (13%) died. Thus, EEG is shown to
      reflect well functional recovery in stroke patients.

PMID- 9513366
TI  - [Cell death induced by noradrenaline in cultured chick spinal cord neurons].
AB  - There is accumulating evidence that some substances which are originally
      transmitters affect neuronal development. Though noradrenaline (NA) containing
      neurons in the brain-stem innervate motoneurons as well as interneurons in the
      spinal cord, little is known about whether or not NA may play roles other than
      neurotransmission during development. Therefore, we have examined the effects of
      NA on developing neurons in the spinal cords of chick embryos. The dissociated
      cells were incubated with chemicals and the number of surviving cells was counted
      2 days later. It was found that NA induced cell death in a dose dependent manner
      (EC50, 13 microM). Phentolamine, an alpha-adrenoceptor antagonist, prevented the
      cell death induced by NA (KD, 1.5 nM), whereas, alprenolol, a beta-adrenoceptor
      antagonist, did not. Furthermore, prazosin, an alpha 1-adrenoceptor antagonist,
      prevented the NA-induced cell death, but yohimbine, an alpha 2-adrenoceptor
      antagonist, did not. Dithiothreitol, an antioxidant, did not prevent NA-induced
      cell death. These results indicate that NA induces cell death in the developing
      neurons in the chick spinal cord through alpha 1-adrenoceptors.

PMID- 9513367
TI  - Systemic and pulmonary responses of inflammatory cytokines following
      esophagectomy.
AB  - Inflammatory cytokines in plasma and bronchoalveolar lavage fluid (BALF) from 16
      post-esophagectomy patients with and without preoperative methylprednisolone
      administration were studied. Interleukin-8 (IL-8), interleukin-6 (IL-6) and tumor
      necrosis factor-alpha (TNF-alpha) concentrations in plasma and BALF were measured
      by ELISA immediately after surgery (0-POD) and on the postoperative day 1 (1
      POD). In patients without methylprednisolone treatment, IL-8 levels in BALF were
      362 +/- 67 pg/ml on 0-POD and 948 +/- 359 pg/ml on 1-POD, and were approximately
      10 times higher than those in plasma levels. IL-6 levels in plasma were
      significantly higher than those in BALF. The TNF-alpha concentration was
      similarly low in plasma and BALF. The patients with preoperative
      methylprednisolone treatment had significantly lower IL-8 levels in BALF and
      plasma compared with the patients without the treatment. Immunocytochemically,
      each cytokine was identified in the cytoplasm of bronchoalveolar macrophage. The
      percentage of polymorphonuclear cells (PMN) among BAL cells was significantly
      increased on 1-POD when compared with that of 0-POD, and tended to be decreased
      by preoperative methylprednisolone treatment. These results suggest that IL-6 was
      markedly increased in the peripheral circulation and that increased pulmonary IL
      8 might be related to an accumulation of PMN in the lung under surgical stress.
      Further, methylprednisolone administration could possibly reduce postoperative
      cytokine responses at the local and systemic levels.

PMID- 9513368
TI  - [Improvement of insulin sensitivity after renal transplantation measured by a
      glucose clamp technique].
AB  - There is much evidence indicating that indicates end-stage renal failure induces
      insulin resistance. We examined the effects of renal transplantation on insulin
      resistance with an insulin clamp technique. Insulin sensitivity and insulin
      secretion rates were measured in 13 renal transplant patients, 7 hemodialysis
      patients, and 6 healthy controls. Insulin sensitivity was assessed with the
      euglycemic insulin clamp technique. The clamp was applied for 120 minutes and the
      average of the glucose disposal rates measured from 90 to 120 minutes was
      regarded as insulin sensitivity. There was a significant increase in the glucose
      disposal rate in the renal transplantation patients (6.67 +/- 1.44 mg/kg/min)
      compared to the hemodialysis patients (4.54 +/- 1.44 mg/kg/min) (p < 0.05). Also,
      there was a significant decrease in the glucose disposal rates in the
      hemodialysis patients (4.45 +/- 1.44 mg/kg/min) compared to the healthy controls
      (7.25 +/- 2.07 mg/kg/min) (p < 0.05). There was no significant difference in the
      glucose disposal rates between the renal transplant patients and the healthy
      controls. However, patients treated with beta-blockers had lower glucose disposal
      rates compared to patients without beta-blockers (4.67 +/- 1.58 vs 6.67 +/- 1.44
      mg/kg/min, p < 0.05). In this study, we found that insulin resistance, shown by
      the euglycemic insulin clamp technique, was recovered after successful renal
      transplantation that but, beta-blockers affected insulin resistance. In
      conclusion shows that, the hyperglycemic clamp technique, although many factors
      such as medication may affect insulin sensitivity, renal transplantation restores
      insulin resistance found in renal failure patients, but not insulin secretion.

PMID- 9513369
TI  - Spigelian hernia: case report.
AB  - A spigelian hernia is an uncommon hernia of the anterior abdominal wall. We
      herein report a case of spigelian hernia, pre-operatively diagnosed as an
      incisional hernia. A 61-year-old woman had undergone an abdominal hysterectomy 14
      years prior to her admission to our hospital complaining of a left lower
      abdominal mass with recurring pain. At the time of the operation the hernial
      orifice appeared not to be related to her previous surgical scar, but was located
      at the spigelian fascia below the level of the umbilicus. The hernial sac was
      dissected and the defect of the abdominal wall was closed. The diagnosis of a
      spigelian hernia can be difficult because of its nonspecific clinical findings
      and insidious nature. Diagnostic procedures and differential diagnosis are herein
      discussed with a review of the literature.

PMID- 9513370
TI  - [Febrile convulsion and related epileptic syndromes].

PMID- 9513371
TI  - [Cardiovascular catheter intervention in children].

PMID- 9513372
TI  - [Recurrence of hepatocellular carcinoma and its treatment].

PMID- 9513373
TI  - Molecular cloning and functional expression of the human heart inwardly
      rectifying potassium channel.

PMID- 9513374
TI  - On the mechanism of pharmacological modification of the human heart stretch
      activated chloride channel.

PMID- 9513375
TI  - Musing of the feline hepatic voltage-dependent delayed-rectifier potassium
      channel gating.

PMID- 9513376
TI  - [Niceritrol decreases serum phosphate levels in chronic hemodialysis patients].
AB  - Since phosphorus retention in hemodialysis (HD) patients is known to be an
      important factor in the development of secondary hyperparathyroidism and renal
      osteodystrophy, phosphate binders have been needed for the control of serum
      phosphate levels (P). However, the calcium-containing phosphate binders that have
      been used widely can cause a rise in serum calcium levels and cause secondary
      hypoparathyroidism. We have recently experienced decreases in P after the
      administration of niceritrol (NT), a prodrug of nicotinic acid, for the treatment
      of low HDL-cholesteremia (HDL-C) in HD patients. The aim of the present study was
      to assess the mechanism of the P-lowering effect of NT in comparison with nicomol
      (NC), another prodrug of nicotinic acid. NT (750 mg/day) or NC (600 mg/day) was
      given orally to 10 or 14HD patients respectively. Blood samples were collected
      before the first dialysis of each week for the determination of serum urea
      nitrogen (UN), Cr, Ca, P, total cholesterol (TC), triglyceride (TG) and HDL-C.
      Serum nicotinic acid concentration (NAC) by gas chromatograph mass-spectrometry
      method was determined before, 4 weeks and 8 weeks after the administration of
      these drugs. After NT administration, P was decreased from 6.2 +/- 0.4 mg/dl to
      5.1 +/- 0.4 mg/dl (1st week, p < 0.001, Mean +/- SE) and 4.5 +/- 0.3 mg/dl (2nd
      weeks, p < 0.001) with no change in UN, Cr or Ca levels; these significant
      decreases in P lasted for 8 weeks. NAC increased significantly after NT
      administration from 25.5 +/- 1.3 ng/ml to 549.8 +/- 102.2 ng/ml (4 weeks, p <
      0.01) and 431.7 +/- 51.4 ng/ml (8 weeks, p < 0.01). HDL-C also increased (33.6 +/
      4.0 mg/dl vs 42.7 +/- 4.6 mg/dl, p < 0.05), but TC and TG did not change. In
      contrast, no significant changes were observed in P, NAC and HDL-C after NC
      administration. These discrepancies could be ascribed to the differences in serum
      NAC levels. These data suggest that NT could be useful for the control of P in HD
      patients. However further studies are needed to confirm the mechanism of the P
      lowering effect of NT.

PMID- 9513377
TI  - [Effects of folic acid supplementation on hyperhomocysteinemia in CAPD patients:
      effects on unsaturated fatty acids].
AB  - Hyperhomocysteinemia has been recognized as one of the risk factors for
      atherosclerosis and premature vascular disease. Patients on dialysis and end
      stage renal disease also manifest high plasma concentrations of homocysteine. We
      performed this study to evaluate the effects of folic acid supplementation on
      hyperhomocysteinemia in CAPD patients. Twenty-three CAPD patients (8 males, 15
      females, 49.1 +/- 14.2-years-old) dialyzed for 22.7 +/- 19.2 months participated
      in the study. Daily 5-mg doses of folic acid supplementation for 4 weeks
      significantly reduced plasma concentrations of total homocysteine (p < 0.01) and
      serine (p < 0.001). This observation suggests that the reduction of plasma
      concentrations of total homocysteine results from activation of homocysteine
      remethylation to methionine. On the other hand, folic acid supplementation also
      revealed significant correlations between changes in serum concentrations of both
      dihomo-gamma-linolenic acid and arachidonic acid and changes in plasma
      concentrations of total homocysteine (r = -0.517, p < 0.05, r = -0.451, p < 0.05,
      respectively). In addition, serum concentrations of both dihomo-gamma-linolenic
      acid and arachidonic acid in 11 CAPD patients with hyperhomocysteinemia (> or =
      35 micromol/litter) were significantly lower than those of 12 CAPD patients with
      normohomocysteinemia (< 35 micromol/litter) (p < 0.05, p < 0.05, respectively).
      Serum concentrations of both dihomo-gamma-linolenic acid and arachidonic acid in
      CAPD patients with hyperhomocysteinemia increased significantly (p < 0.01, p <
      0.05, respectively) and reached similar levels of CAPD patients with
      normohomocysteinemia, while plasma concentrations of total homocysteine decreased
      after folic acid supplementation. These findings suggest that correction of
      hyperhomocysteinemia in patients on dialysis produces an increase in unsaturated
      fatty acids.

PMID- 9513378
TI  - [Acute renal failure in non-fulminant acute hepatitis without hepatitis A, B or C
      virus infection].
AB  - Here, we report a 35-year-old man with non-fulminant acute non A, non B, non C
      hepatitis which developed into acute renal failure. The patient was admitted to
      hospital with the chief complaints of general fatigue, nausea and a high-grade
      fever of 40 degrees C. Laboratory examination revealed severe liver dysfunction
      and renal insufficiency on admission: his serum glutamic oxaloacetic transaminase
      was 3.203 IU/ml, serum glutamic pyruvic transaminase was 3.825 IU/ml, lactic
      dehydrogenase was 2.840 IU/ml, blood urea nitrogen was 65 mg/dl, and creatinine
      was 7.6 mg/dl. Hemodialysis was conducted during the initial 19-day period after
      admission because anuria was manifested on admission. On the 36th day after
      onset, renal functions returned to normal and the patient was negative for IgM-HA
      antibody. HBs antigen, IgM-HBC antibody, HCV antibody, cytomegalovirus antibody,
      and Epstein-Barr virus antibody. However, liver biopsy for histological
      examination on the 44th day after onset revealed no specific findings except the
      healing stage of acute hepatitis. Renal biopsy on the 49th day showed the healing
      stage of acute tubular necrosis without any glomerular change. It has been
      infrequently reported that acute renal failure develops following a non-fulminant
      acute state without hepatitis A, B or C virus infection. It is necessary to take
      acute renal failure into account in the clinical course of non-fulminant non A,
      non B, non C hepatitis.

PMID- 9513379
TI  - [A case of acute renal failure caused by rhabdomyolysis with thrombosis of the
      deep vein of the right leg, following sleeping in a straight sitting position for
      a long time].
AB  - A 41-year-old woman took an overdose of sedatives on the 13th of January, 1994
      and remained a sleep in the straight sitting position until she was woken up on
      the 15th. The next day she consulted our hospital complaining of pain and
      swelling of her right leg. X-ray examination with contrast medium revealed
      obstruction of the deep vein of her right leg by a thrombus. On the 17th, her
      serum urea nitrogen was 75.9 mg/dl and creatinine was 5.4 mg/dl accompanied by
      oliguria. The myoglobin value was 27,000 ng/ml in serum and 88,000 ng/ml in
      urine. She was diagnosed as acute renal failure caused by rhabdomyolysis and
      hemodialysis therapy was started. She was released from hemodialysis on the 31th
      of January. The swelling of her right leg disappeared at the end of February.
      However, her right foot was affected paralysis of the fibular nerve.
      Electromyogram of her right anterotibial muscle and the test of conduction
      velocity of right tibial nerve revealed that the neurological disturbance of her
      right leg was caused by thrombosis of the deep vein. Generally speaking, the
      swelling of the extremities resulting from rhabdomyolysis caused by crush
      syndrome is due to a massive shift of body-fluid into the crushed muscles. We
      believe that when the extremities are compressed (and/or crushed) for a long
      time, venous thrombosis of the extremities occurs due to compression, there by
      causing swelling of the compressed extremities, as in this case.

PMID- 9513380
TI  - [Case report of a recurrent nephrotic syndrome patient with sudden onset of
      blindness during treatment with cyclosporin A].
AB  - We report a case of recurrent nephrotic syndrome with transient blindness after
      taking cyclosporin A (CsA). Renal biopsy showed minimal change of nephrotic
      syndrome and the patient was treated with predonisolone (PSL) and
      cyclophosphamide leading to remission of nephrosis. CsA was given to the patient.
      Because of recurrence of nephrotic syndrome after tapering off PSL to 5 mg a day,
      12 days after taking CsA, the patient complained of sudden onset of left eye
      blindness lasting for 30 minutes. When the patient visited our hospital, the
      disturbed vision had recovered already and there were no abnormal neurological
      findings, such as tremors and seizures. Funduscopic examination revealed no
      evidence of abnormalities and brain computerized axial tomography was
      unremarkable. From these findings, we predicted that constriction of an artery
      and temporarily formed thromboembolization in an eyeground artery had caused the
      sudden vision disturbance. Even though there is a high incidence of thrombotic
      complications in cases of nephrotic syndrome, we believe that vascular
      constriction and formation of thrombi in the eyeground artery of the case were
      mediated by the pathogistic effects of CsA. Because actions in association with
      CsA may produce constriction of small arteries, there by decreasing blood flow,
      initiating coagulopathy and causing endothelial cell damage, all these effects
      may lead to the formation of thrombo-embolic complications. In addition, when
      using CsA for the treatment of nephrotic syndrome, anti-platelets and/or anti
      coagulant medicines should be concomitantly prescribed to avoid the thrombo
      embolic complications.

PMID- 9513381
TI  - [Several problems in the clinical aspects of diabetes mellitus].

PMID- 9513382
TI  - [Assay of blood glucose level, and source of the error].

PMID- 9513383
TI  - [Insulin].

PMID- 9513384
TI  - [Proinsulin, des31-32 proinsulin].

PMID- 9513385
TI  - [C-peptide in blood].

PMID- 9513386
TI  - [Anti-insulin antibody].

PMID- 9513387
TI  - [Islet cell antibody and islet cell surface antibody in diabetics].

PMID- 9513388
TI  - [Anti insulin receptor antibody].

PMID- 9513389
TI  - [Glycohemoglobin (HbA1c, HbA1)].

PMID- 9513390
TI  - [Standardization for glycohemoglobin (HbA1c) measurements and its evaluation].

PMID- 9513391
TI  - [1,5-Anhydroglucitol (1,5AG)].

PMID- 9513392
TI  - [Glycated serum protein (GSP) glycated albumin (GA) and fructosamine].

PMID- 9513393
TI  - [Blood level of ketone bodies].

PMID- 9513394
TI  - [Glycated low density lipoprotein].

PMID- 9513395
TI  - [Growth hormone].

PMID- 9513396
TI  - [Alpha 1-antitrypsin in patients with diabetes mellitus].

PMID- 9513397
TI  - [alpha 2-Macroglobulin].

PMID- 9513398
TI  - [Sialic acid in patients with diabetes mellitus].

PMID- 9513399
TI  - [Insulin-like growth factor I in diabetes].

PMID- 9513400
TI  - [Lewis antigens and CA19-9].

PMID- 9513401
TI  - [Evaluation of lipid peroxides in diabetes mellitus].

PMID- 9513402
TI  - [Clinical significance of serum prolyl hydroxylase in diabetic microangiopathy].

PMID- 9513403
TI  - [Myo-inositol].

PMID- 9513404
TI  - [Serum laminin and collagen in diabetes mellitus].

PMID- 9513405
TI  - [Thrombomodulin in blood].

PMID- 9513406
TI  - [Coenzyme Q10].

PMID- 9513407
TI  - [Neutral proteases of human leucocytes].

PMID- 9513408
TI  - [Superoxide dismutase].

PMID- 9513409
TI  - [Erythrocyte (Na(+)-K+) ATPase activity].

PMID- 9513410
TI  - [Erythrocyte sorbitol, sorbitol dehydrogenase (SDH) and glyceraldehyde reductase
      (GAR) in diabetes mellitus].

PMID- 9513412
TI  - [Advanced glycation endproduct (AGE)].

PMID- 9513411
TI  - [Glycated erythrocyte membrane protein].

PMID- 9513413
TI  - [Autoantibodies against GAD and GAD65].

PMID- 9513414
TI  - [Brain natriuretic peptide and C-type natriuretic peptide].

PMID- 9513415
TI  - [Dehydroepiandrosterone sulfate].

PMID- 9513416
TI  - [Soluble VCAM-1].

PMID- 9513417
TI  - [1 alpha,25(OH)2D3 in blood].

PMID- 9513418
TI  - [Osteocalcin in blood].

PMID- 9513420
TI  - [Tissue inhibitors of metalloproteinases (TIMPs) in blood].

PMID- 9513419
TI  - [Cardiac troponin T].

PMID- 9513421
TI  - [Erythropoietin--a novel marker reflecting the severity of tubulointerstitial
      damage in diabetic nephropathy].

PMID- 9513422
TI  - [Autoantibodies to gangliosides and sulphatides in diabetic patients].

PMID- 9513423
TI  - [Polymorphonuclear leukocyte elastase].

PMID- 9513424
TI  - [Myeloperoxidase].

PMID- 9513425
TI  - [Erythrocyte Na+/Li+ countertransport activity].

PMID- 9513426
TI  - [Secreted protein acidic and rich in cysteine].

PMID- 9513427
TI  - [RLP-C (remnant-like particle cholesterol)].

PMID- 9513429
TI  - [Urinary glucose and other sugars].

PMID- 9513428
TI  - [Serum carboxy-terminal propeptide of human type 1 procollagen (P1CP)].

PMID- 9513430
TI  - [Glycated albumin, non-glycated albumin].

PMID- 9513431
TI  - [Acid soluble protein].

PMID- 9513432
TI  - [Urine C-peptide].

PMID- 9513433
TI  - [Urinary transferrin].

PMID- 9513434
TI  - [Urinary alpha 1-microglobulin and beta 2-microglobulin in diabetes mellitus].

PMID- 9513435
TI  - [N-acetyl-beta-D-glucosaminidase].

PMID- 9513436
TI  - [Urine level of ketone bodies and its clinical significance].

PMID- 9513437
TI  - [Proteoglycans].

PMID- 9513438
TI  - [Urinary alanine aminopeptidase in diabetic patients].

PMID- 9513439
TI  - [Glycylprolyl dipeptidyl aminopeptidase (GP-DAP)].

PMID- 9513440
TI  - [Urinary alpha 2-macroglobulin excretion rate in type 2 diabetic patients].

PMID- 9513441
TI  - [Kappa light chain].

PMID- 9513442
TI  - [Urinary fibronectin degradation products].

PMID- 9513443
TI  - [Thrombomodulin in urine].

PMID- 9513445
TI  - [Fibrinogen degradation products].

PMID- 9513444
TI  - [Urinary excretions of laminin and collagens].

PMID- 9513446
TI  - [Urinary type IV collagen].

PMID- 9513447
TI  - [Diabetic nephropathy and TGF-beta].

PMID- 9513448
TI  - [alpha 1-Acido glycoprotein].

PMID- 9513449
TI  - [Glutathione S-transferase (GST)].

PMID- 9513450
TI  - [Measurement of urinary nitric oxide (NO) in patients with diabetes mellitus].

PMID- 9513451
TI  - [Urinary N-acetyl-beta-D-glucosaminidase (NAG) in patients with diabetes
      mellitus].

PMID- 9513452
TI  - [Urinary D-amino acid oxidase in diabetic patients].

PMID- 9513453
TI  - [Advanced glycation endproduct (AGE)].

PMID- 9513454
TI  - [Tissue inhibitors of metalloproteinases (TIMPs) in urine].

PMID- 9513455
TI  - [Various glucose tolerance test (50 g, 75 g and 100 g) and diagnostic criteria].

PMID- 9513456
TI  - [Analysis of oral glucose tolerance test].

PMID- 9513457
TI  - [Estimation of insulin sensitivity in vivo using glucose clamp and minimal
      model].

PMID- 9513458
TI  - [Polygraphy in diagnosis of diabetic neuropathy].

PMID- 9513459
TI  - [Heart rate variation test in diagnosis of diabetic neuropathy].

PMID- 9513460
TI  - [Measurement of perspiration in patients with diabetes mellitus].

PMID- 9513461
TI  - [Squatting test].

PMID- 9513462
TI  - [Sympathetic skin response (SSR)].

PMID- 9513463
TI  - [Sensory perception test and nerve conduction study in diabetes mellitus].

PMID- 9513464
TI  - [Acceleration plethysmogram].

PMID- 9513465
TI  - [Aortic pulse wave velocity].

PMID- 9513466
TI  - [Carotid wall thickness].

PMID- 9513467
TI  - [Auditory brainstem response (ABR)].

PMID- 9513468
TI  - [Diurnal rhythm of blood pressure in diabetes mellitus].

PMID- 9513469
TI  - [The measurement of the peripheral vascular flow by imaging techniques].

PMID- 9513470
TI  - [Intrarenal resistive index (RI) from renal duplex Doppler sonography in diabetic
      patients with nephropathy].

PMID- 9513471
TI  - [Evaluation of the metabolic dysfunction in various organs with imaging study].

PMID- 9513472
TI  - [Body mass index, body fat percentage].

PMID- 9513473
TI  - [Diabetes mellitus caused by a A to G transition at 3243 of the mitochondrial
      gene].

PMID- 9513474
TI  - [Diabetes mellitus with mitochondrial DNA tRNA(Leu)(UUR) mutation at 3256(C-T)].

PMID- 9513475
TI  - [Diabetes mellitus with mitochondrial DNA tRNA(Leu)(UUR) mutation at 3264(T-
      >C)].

PMID- 9513476
TI  - [Diabetes mellitus with cytochrome c oxidase deletion and mtDNA abnormality].

PMID- 9513477
TI  - [Morphological and histological in situ studies on tissues from patients with
      mitochondrial diabetes mellitus (MDM)].

PMID- 9513478
TI  - [Diabetes caused by glucokinase mutation].

PMID- 9513479
TI  - [MODY (maturity-on-set diabetes of the young)].

PMID- 9513480
TI  - [Insulinopathy].

PMID- 9513481
TI  - [The syndromes of insulin resistance (type A and B)].

PMID- 9513483
TI  - [Glucose intolerance in liver disease].

PMID- 9513482
TI  - [Impaired glucose metabolism in pancreatic diseases and pancreatic surgery].

PMID- 9513484
TI  - [Glucose intolerance in gastrointestinal disease].

PMID- 9513485
TI  - [Hemochromatosis].

PMID- 9513486
TI  - [Myotonic dystrophy].

PMID- 9513487
TI  - [Glucose intolerance in patients with chronic renal failure].

PMID- 9513488
TI  - [Obesity and genesis of glucose intolerance].

PMID- 9513489
TI  - [Glucose intolerance due to diseases of the pituitary].

PMID- 9513490
TI  - [Glucose intolerance in thyroid diseases].

PMID- 9513491
TI  - [Carbohydrate metabolism in glucocorticoid excess].

PMID- 9513492
TI  - [Glucagonoma and somatostatinoma].

PMID- 9513493
TI  - [Abnormal glucose tolerance induced by drugs and chemicals].

PMID- 9513494
TI  - [Relationship between interferon therapy and glucose tolerance].

PMID- 9513495
TI  - [Genetic syndromes associated with glucose intolerance].

PMID- 9513496
TI  - [Animal models of diabetes mellitus: an overview].

PMID- 9513497
TI  - [NOD mouse (non-obese diabetic mouse)].

PMID- 9513498
TI  - [GK rat].

PMID- 9513499
TI  - [WBN/Kob rat].

PMID- 9513500
TI  - [Diabetes mellitus in suncus: EDS (early-onset diabetes in suncus) colony].

PMID- 9513501
TI  - [KK and KK-Ay strains of mice].

PMID- 9513502
TI  - [ob/ob mouse].

PMID- 9513503
TI  - [Wistar fatty rat].

PMID- 9513504
TI  - [OLETF rat. Otsuka Long-Evans-Tokushima Fatty].

PMID- 9513505
TI  - [Streptozocin-induced diabetes].

PMID- 9513506
TI  - [IRS-1 knockout mouse].

PMID- 9513507
TI  - [Glucokinase knockout mice].

PMID- 9513508
TI  - [Effects of transgenic expression of human aldose reductase on diabetic
      complications].

PMID- 9513509
TI  - [Rapid measurement of blood glucose: a survey].

PMID- 9513510
TI  - [Evaluation of portable glucometer and it's clinical usefulness].

PMID- 9513511
TI  - [Portable blood glucose meters using the enzyme electrode].

PMID- 9513512
TI  - [Table of standard body weight].

PMID- 9513513
TI  - [Recommended dietary allowances for Japanese (5th revision)].

PMID- 9513514
TI  - [Food exchange lists (5th ed) for diabetic patients in Japan].

PMID- 9513515
TI  - [Food exchange lists for meal planning in the patients with diabetic
      nephropathy].

PMID- 9513516
TI  - [Diabetes mellitus control by Ministry of Health and Welfare].

PMID- 9513517
TI  - [The policy for diabetes of local government].

PMID- 9513518
TI  - Long-term benefits of internal thoracic artery-coronary artery bypass in Japanese
      patients.
AB  - OBJECTIVES: This study sought to determine the effects of grafting the internal
      thoracic artery (ITA) to the left anterior descending coronary artery (LAD) on
      long-term (10-year) survival, the cardiac death-free rate, and on the cardiac
      event-free rate in Japanese patients. BACKGROUND: The use of ITA grafts has been
      reported to enhance postoperative survival and to decrease the occurrence of
      cardiac events in the Western literature. However, the survival benefits in
      Japanese patients, who may have different prognoses with coronary artery disease
      and a different fate of a saphenous vein graft, have not yet been determined.
      SUBJECTS AND METHODS: A total of 954 consecutive patients who underwent coronary
      artery bypass graft operations (CABG) during the last 12 years at the Nara
      Medical University were followed and evaluated. Of these, 713 patients underwent
      ITA-CABG to at least the LAD (ITA group), and 241 patients received a saphenous
      vein graft (SVG) to the LAD (SVG group). At the time of operation, no significant
      difference was found between these two groups in age, sex ratio left ventricular
      ejection fraction, left ventricular end-diastolic pressure, cardiac index,
      incidence of unstable angina, or in the necessity for an emergency operation.
      However, those patients who received ITA-CABG had significantly higher incidences
      of diabetes mellitus, hyperlipidemia, and left main coronary artery disease.
      RESULTS: The 10-year cumulative graft patency rate for the LAD was 23% higher in
      the ITA group (90.3%) compared to the SVG group (67.0%), (p < .0001). Despite
      increased preoperative risk factors, patients in the ITA group showed significant
      improvements in their 5- and 10-year cumulative survival rates as well as in
      their cardiac death-free and event-free rates. Furthermore, this study
      demonstrated that ITA grafts improved the prognoses of patients with diabetes
      mellitus or left ventricular dysfunction and lowered both the long-term
      postoperative cardiac-death rate and the cardiac-event rate. CONCLUSIONS: The use
      of ITA grafts was effective in improving both the postoperative survival and
      cardiac event-free rates, and should be recommended in patients with diabetes
      mellitus or left ventricular dysfunction. ITA grafting to the LAD should be a
      routine operation in almost all categories of such patients.

PMID- 9513520
TI  - [The effect of pump flow on cerebral oxygen metabolism during cardiopulmonary
      bypass].
AB  - We evaluated effects of pump flow on cerebral metabolism using transcranial
      Doppler (TCD) during cardiopulmonary bypass (CPB) in 22 adult patients undergoing
      coronary artery bypass grafting. All the patients were anesthetized with high
      dose fentanyl. The pump flow was controlled with non-pulsatile roller pump at 2.2
      2.5 L/min/m2 in group L and 2.7-3.0 L/min/m2 in group H under alpha-stat acid
      base regulation. Pharyngeal temperature was kept at 31 degrees C in steady CPB
      state. Mean velocity of middle cerebral artery (MCAV) was monitored with TCD
      fixed on the temple continuously. Cerebral oxygen consumption was estimated by
      relating the difference in oxygen content between arterial and venous (jugular
      bulb) blood (AVDO2) to flow velocity. In group L, blood oxygen saturation of
      jugular bulb (SjO2) was stable during hypothermic period, but decreased
      significantly during rewarming period. In group H, SjO2 was significantly
      increased with cooling, but went down to preoperative level during rewarming
      period. Significant difference of SjO2 between two groups was noticed in
      rewarming period (52.9 +/- 10.0% in group L and 65.6 +/- 11.8% in group H, p =
      0.0133). MCAV tended to decrease with cooling and increase with rewarming, but
      which was not significant change respectively. Relative cerebral metabolic rate
      for oxygen (rCMRO2) was defined as the percent change of the product AVDO2 and
      MCAV. In each group, rCMRO2 was decreased with cooling and increased with
      rewarming significantly. Especially, rCMRO2 right after CPB discontinued was
      increased 1.7 times in L group and 2.0 times in group H as much as that of steady
      state of CPB. It is suggested that cerebral metabolism should be decreased during
      cooling to 31 degrees C of pharyngeal temperature, 2.2-2.5 l/min/m2 of pump flow
      was adequate to keep SjO2 stable. On the other hand, it is necessary to increase
      pump flow to 2.7-3.0 l/min/m2 during rewarming period as cerebral oxygen
      metabolic demand becomes greater.

PMID- 9513519
TI  - Clinical evaluation of adjuvant chemoradiotherapy with CDDP, 5-FU, and VP-16 for
      advanced esophageal cancer.
AB  - OBJECTIVES: The aim of this study was to evaluate the efficacy of adjuvant
      chemoradiotherapy following surgery in patients with advanced esophageal cancer.
      SUBJECTS AND METHODS: We followed the cases of 57 such patients treated at our
      hospital, involving 19 who received adjuvant chemoradiotherapy (CR group), 19 who
      received radiotherapy alone (R group), and 19 who did received neither (N group).
      In the CR group, chemotherapy, consisting of cis-diaminodichloroplatinum (CDDP),
      5-fluorouracil (5-FU), and etoposide (VP-16), was combined with radiotherapy was
      administered from 4 weeks after surgery. Concurrent radiotherapy was started at 3
      weeks after esophagectomy. CDDP at 50 mg/m2 was administered on days 1 and 7.5-FU
      at 500 mg/m2 and VP-16 at 60 mg/m2 were administered on days 3, 4, and 5.
      Thirteen patients (68.4%) were treated with more than 2 cycles of chemotherapy
      combined with radiation. RESULTS: Side-effects of severe anorexia (grade 3) and
      leukocytopenia (< 1900/microliter) were observed in 47% and 39% of the patients,
      respectively. However no treatment-related death was observed. The 5-year
      survival rate was 25.2%, 18.9%, and 15.8%, in the CR group, R group, and N group,
      respectively. The recurrence rate was 66.7% in the CR group, which was higher
      than in the matched control groups (46.2% in the N group and 54.5% in the R
      group), but with no a significant difference. CONCLUSION: These results suggested
      that adjuvant chemoradiotherapy did not contribute to improvement in prognosis
      for these patients with advanced esophageal cancer.

PMID- 9513521
TI  - [Reoperative coronary artery bypass grafting without cardiopulmonary bypass].
AB  - Between October 1995 and February 1997, 2 men and 4 women aged 53 to 75 years
      (mean, 66.3) underwent reoperative coronary artery bypass grafting without
      cardiopulmonary bypass. Isolated reoperative circumflex or intermediate artery
      bypass was performed through a left thoracotomy (n = 2), reoperative bypass to
      the left anterior descending coronary artery was performed through a median
      sternotomy (n = 3), and bypass to the right coronary artery was performed through
      an upper median laparotomy (n = 1). Single coronary bypass grafting utilizing
      arterial grafts (left internal thoracic artery: 3, right gastroepiploic artery:
      3) was performed in all cases. There were no operative deaths. All cases required
      neither cathecolamine nor intraaortic balloon pumping). Peri/post operative blood
      transfusion was necessary in only one case. Postoperative coronary angiography
      revealed that the 6 arterial grafts were patent. Reoperative coronary artery
      bypass grafting without cardiopulmonary bypass can be performed with low
      perioperative morbidity and mortality, easy postoperative management,
      satisfactory graft patency, and good symptomatic improvement.

PMID- 9513522
TI  - [The oxygen transporting capability of neo red cells (NRC) evaluated under total
      cardiopulmonary bypass].
AB  - The oxygen transporting capability of an artificial oxygen carrier NRC was
      evaluated by employing it as a perfusate for total cardiopulmonary bypass. NRC is
      a type of liposome encapsulated hemoglobin. It has a particle size of
      approximately 220 nm, with a hemoglobin concentration of 5.6 g/dl and its P50 is
      controlled to 45 Torr. Male beagles were used in the experiment. Approximately
      80% of the estimated circulatory volume was exchanged with NRC and total
      cardiopulmonary bypass was initiated. Arterial oxygen tension and carbon dioxide
      tension were controlled to 400 Torr and 40 Torr respectively. The perfused we
      heated to 37 degrees C. The rate of flow was altered during the experiment.
      Oxygen consumption reached a plateau at 9.3 ml/kg/min where oxygen delivery was
      14.9 ml/kg/min. At this point the oxygen consumed per gram of hemoglobin from NRC
      was equivalent to that from dog red blood cells. This indicated that almost an
      equal amount of oxygen was consumed from NRC in comparison to red blood cells.
      Regarding oxygen transporting capability, NRC could be considered a candidate for
      perfusate in cardiopulmonary bypass.

PMID- 9513523
TI  - [Strategies for preventing stroke after coronary artery bypass grafting].
AB  - To evaluate the usefulness of our strategy for preventing stroke after CABG, 343
      consecutive patients were investigated retrospectively. Patient ages ranged from
      32 to 31 years (mean; 63 +/- 9 years). There were 254 males and 59 females.
      Number of grafts per patient was 1 to 5 (mean 2.4 +/- 0.9 grafts). In 193
      patients, internal carotid arteries (ICAs) were preoperatively evaluated by
      duplex scanning or cerebral angiogram. The degree of atherosclerosis in the
      ascending aorta was preoperatively examined by plain computed tomography in 181
      patients, during surgery by ultrasonography in 75 patients and palpation in all
      patients. RESULTS: 1. On preoperative examination, there were 26 patients (15.1%)
      with ICA stenosis greater than 50% and 15 patients (7.8%) with stenosis greater
      than 75%. Six patients had bilateral ICA stenosis or occlusion greater than 75%.
      In 26 patients with ICA stenosis greater than 50%, history of stroke was
      significantly more prevalent than that in 167 patients without ICA stenosis (12
      patients: 46.2% vs 22 patients: 13.1%, p < 0.001). In patients with ICA stenosis
      greater than 75%, 6 patients were symptomatic and 8 were asymptomatic. For these
      patients, concomitant carotid endarterectomy and CABG were performed in 5, two
      stage procedures in 7 reconstruction of cerebral perfusion followed by CABG;4,
      followed by CEA: 3), and CABG alone in 3. There was no stroke in any of these
      patients. 2. Atherosclerosis of the ascending aorta was found in 69 of 343
      patients (20.1%). In these patients, single clamp technique was applied in 50
      patients, aortic no touch technique in 12 and CABG without cardiopulmonary bypass
      in one. The arterial cannulation site was changed to femoral artery in 15 and to
      axillary artery in 6 patients. Statistical analysis indicated that age (older
      than 60 years) and history of stroke were significant risk factors for
      atherosclerotic ascending aorta. 3. There were 3 patients (0.9%) with
      perioperative stroke caused by embolism from the ascending aorta in one and
      hypoperfusion of the brain during cardiopulmonary bypass in two. CONCLUSION:
      Proper treatment of atherosclerotic ascending aorta and carotid occlusion may
      reduce the incidence of stroke in CABG patients.

PMID- 9513524
TI  - [Blood flow velocity in the ophthalmic artery measured by Doppler ultrasonography
      during cardiopulmonary bypass--usefulness for cerebral perfusion monitor].
AB  - Brain blood flow is supplied from the internal carotid artery, and the ophthalmic
      artery is the first branch of the internal carotid artery. We studied how blood
      flow velocity in the ophthalmic artery (OAV) changes during cardiopulmonary
      bypass (CPB) and investigated whether it can be used to monitor brain blood flow
      during CPB. In 13 open heart surgeries in adults, OAV and blood flow velocity in
      the common carotid artery (CAV) were measured with Doppler ultrasonography, and
      blood flow volume in the brachiocephalic artery (BA flow) was measured
      simultaneously with an electromagnetic flow meter. Maximal blood flow velocity in
      the ophthalmic artery (OAVmax) and the common carotid artery (CAVmax) were 0.27
      +/- 0.13 m/sec and 0.64 +/- 0.40 m/sec, BA flow was 486 +/- 226 ml/min before
      CPB. When CPB pump flow was varied (2.4, 2.2, 2.0, 2.2, 2.4 l/min/m2), the
      parameters during and after CPB changed as follows (as percentage of pre-CPB
      levels): OAVmax, 58.1%, 50.9%, 37.6%, 49.4%, 64.7%, 108.4%; CAVmax, 67.0%, 58.0%,
      48.2%, 113.6%, 105.5%, 134.3%; and BAflow, 87.3%, 39.8%, 53.9%, 50.5%, 95.0%,
      159.8%. Our results indicate that OAVmax more accurately reflects changes in pump
      flow than does CAVmax and BA flow. Because vessel resistance in the ophthalmic
      artery was small during CPB, OAVmax was thought to be determined mainly by CPB
      pump flow. OAVmax was useful for monitoring brain blood flow during CPB.

PMID- 9513525
TI  - [Pleural adenosine deaminase levels in tuberculous pleurisy--its diagnostic
      performance under the different prevalences in the different age of population].
AB  - In the diagnosis of pleural effusion, tuberculous pleurisy should always be
      considered because the prevalence of tuberculosis in Japan remains high. The
      measurement of adenosine deaminase (ADA) levels in pleural fluid is useful for
      the diagnosis of the tuberculous pleurisy because of its high sensitivity and
      specificity. However, no studies have addressed the post-test probability (=
      positive predictive value; PPV) of the test. Since the PPV depends on the pre
      test probability (= prevalence) of the tuberculous pleurisy that varies with age,
      we have retrospectively evaluated the PPV in the different age population; the
      young (-35 years of age), the middle (36-65 years), and the old (66-years). A
      total of 208 data sets were collected; the tuberculosis (n = 52), malignancy (n =
      34), non-specific infection (n = 31), transudates (n = 45), the others (n = 36),
      and unknown causes (n = 10). It was found that 1) the prevalence of tuberculous
      pleurisy was decreased with age, (70% in the young, 28.7% in the middle, and 8.5%
      in the old), 2) the PPV was the lowest in the old (53.8%), while the highest in
      the young (95.0%), and 3) no significant correlation was found between age and
      the ADA activity in pleural effusion.

PMID- 9513526
TI  - [The propriety of bilateral internal thoracic artery grafting in women].
AB  - In our institution, the exclusion criteria of the bilateral internal thoracic
      artery (BITA) grafting include age over 70 years old, obesity, severe diabetes,
      renal dysfunction and poor preoperative physical activity. The objective of this
      study is to evaluate propriety of the use of bilateral internal thoracic artery
      for coronary artery bypass grafting (CABG) in women. Clinical outcome of female
      patients who underwent BITA grafting (group B-F; n = 50) was compared with that
      of female patients who underwent single internal thoracic artery grafting (group
      S; n = 50). In addition, clinical outcome of the male patients who underwent BITA
      grafting (group B-M; n = 50) was compared with that of group B-F. Between group B
      F and S, the age, prevalence of obesity and that of renal dysfunction were
      significantly different, which was predictable because of the group selection
      according to the criteria. However, the prevalence of previous myocardial
      infarction and that of left ventricular dysfunction and the extent of coronary
      artery disease were not significantly different. Whereas, between group B-F and B
      M, preoperative factors were not significantly different except the body size.
      Intraoperative technical factors, such no of grafts, aortic cross clamp time,
      cardiopulmonary bypass time, rate of complete revascularization, were not
      significantly different. In comparison of group B-F with group B-M, the site of
      anastomosis with arterial grafts were not significantly different. Patency rate
      of arterial and venous grafts two week after operation was not significantly
      different. Either postoperative complications, such as reoperation for bleeding,
      wound complication, low output syndrome, renal dysfunction etc, were not
      significantly different. One patient (2%) in group B-F and 1 patient (2%) in
      group B-M died in the hospital (p > 0.05). In summary, BITA can be a viable
      conduit of choice for CABG in female patients as well as that in male patients.
      Criteria of the use of BITA is recommended to exclude preoperative risk factors
      above-mentioned.

PMID- 9513527
TI  - [Experimental study in partial liquid ventilation for acute respiratory failure
      after ischemia reperfusion pulmonary injury in a rabbit model].
AB  - Partial liquid ventilation (PLV) using perfluorooctylbromide (PFOB) was studied
      for use in treating experimental animal models in which acute respiratory failure
      was caused by hypoxia, oleic acid lung injury, or saline lung lavage. Clinical
      trials are currently being conducted in the United States. We studied the
      effectiveness of PLV with PFOB in treating acute respiratory failure after
      ischemia reperfusion pulmonary injury in a rabbit model; left lung ischemia was
      induced with a hilar clamp. Ninety minute later, the clamp was removed for
      reperfusion. Fifteen Japanese white rabbits weighing from 2.5 to 3.2 kg were
      divided into three groups-conventional mechanical ventilation (CMV) after
      reperfusion, PLV after reperfusion and controls (conventional mechanical
      ventilation without ischemia reperfusion injury). In the PLV group, a dose of 7
      ml/kg PFOB was administered through an endotracheal tube. In the CMV group, PaO2
      value decreased to 79 +/- 13 mmHg 120 min after reperfusion, significantly lower
      than in the PLV group 404 +/- 70- or controls -494 +/- 61-. PaCO2 was
      significantly higher in the CMV group-61.9 +/- 14.4 mmHg- than in the PLV group
      45.7 +/- 6.1- or controls-32.1 +/- 2.2. Peak airway pressure was slightly higher
      in the CMV group-19.0 +/- 4.9-than in the PLV group-18.2 +/- 5.4- or controls
      16.2 +/- 1.8. mPAP/mSAP did not differ significantly among groups. The heart rate
      decreased in the CMV and PLV groups, but was unchanged in controls. Microscopic
      studies revealed markedly reduced alveolar hemorrhage, lung fluid accumulation,
      and inflammatory infiltration in the PLV group, compared to the CMV group. PLV
      thus is effective in improving gas exchange and preventing pulmonary injury in
      acute respiratory failure after ischemia reperfusion injury in a rabbit model.

PMID- 9513528
TI  - [Removal of infected pacemaker lead through sternotomy without cardiopulmonary
      bypass].
AB  - A 66-year-old man, who had undergone DDD pacemaker implantation for complete A-V
      block two years ago, was admitted because of endocarditis with septicemia and
      renal failure. His blood culture revealed Staphylococcus aureus. We tried to
      remove the infected cardiac pacemaker lead. But we failed to remove the atrial
      lead because it was strongly adhered with the right atrial appendage. Antibiotic
      therapy was ineffective. In the last resort, we operated through median
      sternotomy three months after the initial infectious episode. In intraoperative
      inspection, we found it difficult to remove the lead by traction because of
      atrial residual lead sticking out of the right atrial appendage. We applied a
      purse string suture on the right appendage and obtained successful removal of
      infected lead without the cardiopulmonary bypass. His postoperative course has
      been uneventful. He is totally asymptomatic and doing well up to now. In case of
      such local infection, we conclude that all transvenous leads should be removed
      and recommend a simultaneous implantation of the epicardial pacemaker system.

PMID- 9513529
TI  - [Three cases of right-sided active endocarditis with multiple pulmonary
      infarction].
AB  - We have experienced three patients with right-sided active endocarditis combined
      with multiple pulmonary infarction. Ventricular septal defect (VSD), aortic
      regurgitation (AR), tricuspid regurgitation (TR) and congestive heart failure
      were present in case 1. TR was present in case 2. VSD, TR and patent ductus
      arteriosus were present in case 3. alpha-Streptococcus caused endocarditis in
      case 1 and 3; Candida albicans caused endocarditis in case 2. Antibotic therapy
      had no effect in case 2 and 3. Case 1 and 3 developed pulmonary hemorrhage, which
      resolved before the operation in case 1, but not in case 3. Our three patients
      underwent surgery and recovered successfully. They were discharged on the 43th,
      58th and 32th postoperative day and are presently free of clinical symptoms.
      These experiences suggest surgery should be undertaken in the following
      situations: 1. antibiotic therapy has no effect on the infection, 2. hemodynamics
      are worsening, and 3, pulmonary infarction and pulmonary hemorrhage occur
      repeatedly.

PMID- 9513530
TI  - [A case report of aortoesophageal fistula due to thoracoabdominal aortic
      aneurysm].
AB  - Aortoesophageal fistulas due to thoracic aneurysms are usually fatal, with few
      reported survivors. A 57-year-old man with aortoesophageal fistula due to
      thoracoabdominal aortic aneurysm underwent the graft replacement of
      thoracoabdominal aorta. In the postoperative course, prosthetic graft infection
      had occurred in the result of residual esophageal fistula. On the 32nd
      postoperative day (POD), a subtotal esophagectomy was performed and the esophagus
      was reconstructed by gastrointestinal interposition technique via a retrosternal
      route. Following the second operative procedure, inflammatory reactions had been
      improved with systemic administration of antibiotics and continuous irrigation of
      the infected cavity. On 77th POD, he was discharged.

PMID- 9513531
TI  - [Two cases of surgical treatment of recrudescent Stanford type A dissection after
      early thrombogenic closure without intimal tear].
AB  - We reported two cases of thrombosed, Stanford A type acute aortic dissection,
      initially without intimal tear, later operated upon because of recrudescence.
      They admitted to our hospital with the symptoms of aortic dissection. Early
      examination of computed tomography and angiography demonstrated thrombosed type A
      aortic dissection showing a normal aortic figure, although accompanied by
      pericardial effusion, that was drainaged. Under strict BP control, however,
      repeat CT examination revealed recrudescent dissection of ascending aorta, making
      dissecting aneurysms. Graft replacement of ascending aorta was performed, on the
      55th and 153th day after admission, and they were discharged.

PMID- 9513532
TI  - [A successful valve repair case of isolated tricuspid regurgitation due to
      traumatic lacerated papillary muscle of the tricuspid valve].
AB  - A case of tricuspid valve regurgitation due to a non-penetrating chest trauma was
      presented. This case involves a 20-year-old man, who was admitted to a nearby
      hospital because of rib fracture, mandibular fracture, and hemorrhage of the left
      hemopneumothorax, caused by a traffic accident. Palpitation and chest discomfort
      were observed at admission time, but there was no follow-up. Tricuspid
      regurgitation was pointed out during surgery for the mandibular fracture, and he
      continued follow up treatment at an outpatient clinic. However his palpitation
      and chest discomfort worsened, and he was admitted to our department 8 month
      after injury. During surgery to repair the tricuspid valve, a papillary muscle
      rupture, valve cusp laceration, and anulus dilatation were found. We performed a
      papillary muscle repair (chorda tendineae reconstruction), valve cusp suture, and
      annuloplasty. Absence of the left pericardium was observed during the operation.
      We reported valve repair of traumatic tricuspid regurgitation which with
      papillary muscle rupture. Due to its rarity and the fact that there has been no
      reported cases of papillary muscle repair for traumatic tricuspid regurgitation
      in Japan, we used researched information on the subject.

PMID- 9513533
TI  - [A case of total arch replacement for redissected impending rupture of early
      thrombosed aortic dissection without intimal tear detectable at operation].
AB  - A 51-year-old suddenly developed severe chest and back pains. The diagnosis was
      acute aortic dissection of Stanford type A, but the dissecting space was not
      observed by enhanced CT scan. Medical treatment was started as early thrombosed
      aortic dissection. The blood pressure was sufficiently controlled, and the
      symptom was gradually improved. On the 8th hospital day, a severe chest pain
      appeared again, Enhanced CT scan showed an enlarged dissecting space, pericardial
      and pleural effusion. These findings were considered a redissected impending
      rupture, so the emergency operation was performed. Fresh clots were observed in
      the dissecting space of ascending aorta, but the intimal tear was not found in
      any portion of the examined aorta. Therefore total arch replacement was needed to
      resect the wall which may be responsible for the dissection and to reduce the
      residual dissecting space. The patient recovered without complications.
      Postoperative CT scan revealed no residual false lumen in the distal descending
      aorta.

PMID- 9513534
TI  - [Acute aortic dissection after aortic valve replacement].
AB  - A 53-year-old male who had been performed aortic valve replacement 15 weeks
      before was admitted to our hospital because of severe chest pain. Cjest
      computerized tomography showed dissection of aorta from ascending to descendig
      aorta and hemorrhage around ascending aorta. An emergency operation was performed
      under hypothermic circulatory arrest with a selective cerebral perfusion. An
      entry of dissection was found at posterior wall where was 3 cm upper from an
      artificial valve. Total arch replacement was successfully performed. There is a
      few cases of aortic dissection after aortic valve replacement, but careful peri
      and post operative care is necessary after aortic valve replacement.

PMID- 9513535
TI  - [Left ventricular rupture following mitral valve replacement with preservation of
      posterior leaflet].
AB  - Left ventricular rupture following mitral valve replacement (MVR) with
      preservation of the posterior leaflet is presented. A 63-year-old man underwent
      combined AVR, MVR with preservation of the posterior leaflet and TAP under
      cardiopulmonary bypass with moderate hypothermiat to 28 degrees C and tepid blood
      cardioplegia. Although a 31-mm valve would fit to the mitral position, a 27 TEKNA
      was chosen for MVR. Beyond the cardiopulmonary bypass, a left ventricular rupture
      was found. Cardiopulmonary bypass was re-stated and the aortic clamp was
      replaced. After removal of the mitral valve prosthesis, an internal tear was
      detected below the anterolateral commissural area (Type I). The tear was repaired
      with two 3-0 monofilament buttressed sutures incorporated with felt strips and
      covered with a bovine pericardial patch by several interrupted pledgeted mattress
      sutures. Gelatin-resorcin-formaldehyde/Glutaraldehyde glue (GRF) was used to
      reinforce the ruptured myocardium and to fix a bovine pericardial patch to the
      affected ventricular wall. Then the prosthesis was re-seated. Although the aortic
      clamp time was 319 mins., the patient was weaned from the cardiopulmonary bypass
      easily with the prophylactic use of IABP. The patient was discharged and returned
      to his previous job.

PMID- 9513536
TI  - [Mediastinal bronchogenic cyst associated with high serum level of CA19-9--a
      surgical case report].
AB  - We reported a case of mediastinal bronchogenic cyst in a patient with a high
      serum level of CA19-9. The patient, a 41-year-old man, presented with a complaint
      of persistent fever. Chest X-ray examination, computed tomography and magnetic
      resonance imaging showed a subcarinal mass shadow which was diagnosed
      preoperatively as a bronchogenic cyst. The serum level of CA19-9 was 73 U/ml. The
      cyst was partially removed via right thoracotomy. Histopathological findings were
      compatible with bronchogenic cyst. The CA19-9 level in the specimen was 134,00
      U/ml. The serum level of CA19-9 decreased to normal postoperatively. The
      postoperative course was uneventful.

PMID- 9513537
TI  - [High-dose methylprednisolone-containing chemotherapy in advanced invasive
      thymoma--report of three cases].
AB  - During the period from May, 1995 to August, 1996, three patients with Stage III
      or IVa invasive thymoma received chemotherapy consisting of cisplatin,
      doxorubicin and methylprednisolone (1000 mg on days 1 through 5, and 500 mg on
      days 6 and 7). The first case, a 55-year-old woman, who underwent extended
      thymectomy 7 years ago, was found to have a recurrent tumor in the left pleural
      cavity. The second case, a 38-year-old man, who had first operation 3 years ago,
      developed recurrent tumor in the right pleural cavity. These two patients were
      treated with the above regimen as the primary mode of therapy. The third case, a
      61-year-old woman, had a thymoma with direct invasion to right upper lobe. The
      same chemotherapy regimen was employed as the induction chemotherapy. All
      patients showed a major response to treatment with only a small amount of tumor
      remaining. The effectiveness of chemotherapy in the treatment of malignant tumors
      has been recently reported to be at least partly due to induction of apoptosis.
      Steroids are known to induce apoptosis in normal thymic cells, and thus steroid
      in chemotherapy regimen against invasive thymoma may enhance the effect of anti
      cancer drugs through the induction of apoptosis.

PMID- 9513538
TI  - [Repair of intrathoracic visceral damage using video-assisted thoracoscopic
      surgery for blunt chest trauma and rib fixation at the site of mini-thoracotomy].
AB  - We treated three patients with intrathoracic visceral damage caused by severely
      dislocated fractured ribs resulting from blunt trauma by using video-assisted
      thoracoscopic surgery (VATS) and rib fixation through a mini-thoracotomy. Under
      general anesthesia and unilateral respiration, the thoracic cavity was inspected
      with a thoracic video scope through the port inserted through the thoracic
      drainage opening which was made upon arrival at hospital. As the visceral damage
      seemed restorable under VATS, a mini-thoracotomy was positioned just above the
      rib fracture. Two thoracic ports were inserted through the site of rib fracture
      or through the intercostal space and then VATS was performed using three ports.
      After the restoration of intrathoracic visceral damage, the fractured rib was
      fixated using a bioabsorbable poly-L-lactide rib fixation pin or a marlex mesh.
      Lung injuries were sutured and ligated under VATS in two of our cases and a spur
      of the fractured rib was shaved in one case. Only severely dislocated ribs were
      fixated through the mini-thoracotomy in all cases. Air leakage stopped just after
      this procedure and there were no complications. The rib fixation and bone
      regeneration were excellent after this procedure. The advantages of this method
      are the visceral restoration under VATS through a mini-thoracotomy and the
      ability to perform rib fixation without injuries to the intercostal muscle,
      artery, vein or nerve. This operative procedure is recommended for intrathoracic
      visceral damage caused by severely dislocated rib fracture.

PMID- 9513539
TI  - [Use of ultrasonically activated scalpel for the paced patient--a case report].
AB  - A paced patient underwent mitral valve replacement for mitral stenosis using
      ultrasonically activated scalpel. There were minimum bleeding and no homologous
      blood transfusion was required. Ultrasonically activated scalpel fid not
      interfere the pulse generator nor the transesophageal echocardiography.
      Ultrasonically activated scalpel is useful for the open heart surgery in paced
      patients.

PMID- 9513541
TI  - [Sudden death due to genetic and biochemical disorders --long QT syndrome].

PMID- 9513540
TI  - [Sudden death due to genetic and biochemical disorders--hypertropic
      cardiomyopathy].

PMID- 9513542
TI  - [Sudden death due to aortic diseases--special reference to the gene and
      biochemical diagnosis].

PMID- 9513543
TI  - [Sudden death due to genetic and biochemical disorders--idiopathic ventricular
      fibrillation].

PMID- 9513544
TI  - [Physiopathology of sudden death--pulmonary embolism].

PMID- 9513545
TI  - [Physiopathology of sudden death--arrhythmia].

PMID- 9513546
TI  - [Physiopathology of sudden death--myocardial infarction].

PMID- 9513547
TI  - [Physiopathology of sudden death--aortic diseases].

PMID- 9513548
TI  - [Physiopathology of sudden death--cerebrovascular disorders].

PMID- 9513549
TI  - [Physiopathology of sudden death--adverse effects of therapeutic drugs].

PMID- 9513550
TI  - [Physiopathology of sudden death--multivessel coronary artery spasm].

PMID- 9513551
TI  - [Sudden death during sports events].

PMID- 9513552
TI  - [Sudden death and death on arrival].

PMID- 9513553
TI  - [Prevention of sudden death and the countermeasures--emergency cardiopulmonary
      resuscitation].

PMID- 9513554
TI  - [Prevention of sudden death and the countermeasures--cardiac sudden death and
      acute myocardial infarction--ideal emergicenters].

PMID- 9513555
TI  - [Prevention of sudden death and the countermeasures--implantable defibrillators].

PMID- 9513556
TI  - [Prevention of sudden death and the countermeasures--prevention of sudden death
      using anti-arrhythmia agents].

PMID- 9513557
TI  - [Prevention of sudden death and the countermeasures (discussion)].

PMID- 9513558
TI  - [Case of intestinal pseudo-obstruction associated with hypothyroidism].

PMID- 9513559
TI  - [Two cases of myokymia-like muscle movement disorders following administration of
      adrenergic beta-antagonists].

PMID- 9513560
TI  - [Case of disseminating Mycobacterium avium intracellulare infection associated
      with anemia and neck pain].

PMID- 9513561
TI  - [Cytokines and pathogenesis of interstitial pneumonia].

PMID- 9513562
TI  - [Therapeutic agents for Alzheimer's disease].

PMID- 9513563
TI  - [Hepatitis C virus and disease model of Sjogren syndrome].

PMID- 9513564
TI  - [The study of genetic changes in colorectal cancer accompanied with ulcerative
      colitis].
AB  - The usefulness of gene information was studied when used in conjunction with a
      morphological diagnosis of either dysplasia or carcinoma that later develops into
      ulcerative colitis (UC). The cases investigated consisted of those operated on
      for UC with carcinoma complications and those operated on for UC over 7 years
      previously without carcinoma complications. Ras and DCC were examined for the
      presence of any point mutations in codon 12 and polymorphism in codon 201 using
      the PCR-RFLP method, while p53 was also studied immunohistologically. A mutation
      in ras was found in 25% of the UC-IV cases and also in 17% of the UC-III cases,
      while no mutation at all was found in the UC-I and UC-II cases. p53 showed a high
      rate of positivity in the UC-IV and UC-III cases with carcinoma complications,
      while it was negative in all cases in the control group cases. Gly in DCC codon
      201 was also found in many cases including the control group. This study
      demonstrated that a gene aberration can thus influence the pathophysiology and
      cancerization of UC and therefore the p53 findings were thus considered to be
      useful in the morphological diagnosis of dysplasia and carcinoma.

PMID- 9513565
TI  - [Estimation of cell proliferation in hepatocellular carcinoma and in background
      liver cirrhosis, by using MIB-1 LI].
AB  - The 23 hepatectomized patients with hepatocellular carcinoma (HCC) were studied.
      Samples were biopsied from both cancerous portion and from non-cancerous
      cirrhotic portion at operation. MIB-1 LIs were measured in these biopsied
      samples. Then the relationships between MIB-1 LIs and pathologic feature,
      clinical data, and prognosis were investigated. LIs of the cancerous portion
      (10.2 +/- 6.8%, Mean +/- SE) were significantly (p < 0.001) greater than those of
      non-cancerous cirrhotic portion (3.8 +/- 2.1%). LIs of the cancerous portion in
      the patients who were dead with in 18 months after their hepatectomies, were
      significantly (p < 0.05) greater than those in the patients who survived more
      than 18 months after operations. LIs of the cancerous portion in the patients
      whose samples revealed Edmondson & Steiners classification grade III, were
      significantly (p < 0.05) greater than those in the patients whose samples
      revealed grade II. LIs of the cancerous portion in the patients whose serum AFP
      levels showed high level (> or = 100 ng/ml) were significantly (p < 0.005)
      greater than those in the patients whose serum AFP levels showed low level (< 100
      ng/ml). And LIs of the non-cancerous portion in the patients whose thymol
      turbidity test (TTT) showed high level (> 5K-U), were significantly (p < 0.005)
      greater than those in the patients whose TTT levels showed within normal range.
      LIs of the non-cancerous potion in the patients whose zinc sulphate turbidity
      test (ZTT) showed high level (> 12K-U), were significantly (p < 0.01) greater
      than those in the patients whose ZTT levels showed within normal range. LIs of
      the non-cancerous portion in the patients whose PT levels were prolonged (14 sec
      <), were significantly (p < 0.05) greater than those in the patients whose PT
      levels were within range. MIB-1 LIs were proved to be a good marker for
      estimation of biological behaviour of HCC tumors.

PMID- 9513566
TI  - [Follow-up observation of intestinal Behcet disease treated with
      salazosulfapyridine and mesalazine for 8 years and 9 months].

PMID- 9513567
TI  - [Five cases of inflammatory myoglandular polyp].

PMID- 9513568
TI  - [Crohn's disease in monozygotic twins].

PMID- 9513569
TI  - [A case of extrahepatic growing hepatocellular carcinoma which was proven by CT
      findings to be developed from hepatocellular carcinoma of the liver edge].

PMID- 9513570
TI  - [A case of primary malignant fibrous histiocytoma of the gallbladder and a review
      of the cases in Japan].

PMID- 9513571
TI  - [Circular dichroism in the the structural analysis of chiral compounds].

PMID- 9513572
TI  - [Marine organisms--producers of pharmacologically active secondary metabolites].

PMID- 9513573
TI  - [Prodrugs for colon targeting].

PMID- 9513574
TI  - [Molecularly symmetric Mannich bases].

PMID- 9513575
TI  - [Diabetes and hyperglycemia in patients under treatment for HIV infection with
      the protease inhibitors indavir, ritonavir, saquinavir as well as nelfinavir (in
      development, but not yet released].

PMID- 9513576
TI  - [Implant insertion with simultaneous bone augmentation].

PMID- 9513577
TI  - [The Christ-Siemens-Touraine syndrome. The clinical picture, diagnosis, therapy
      and follow-up of hypodontia in ectodermal dysplasia].

PMID- 9513579
TI  - [Pharmacokinetic analysis of scavenger receptor-mediated uptake of
      mucopolysaccharides in various cells].
AB  - Although the scavenger receptor-mediated uptake has been qualitatively
      investigated in the research fields of biochemistry and pathology,
      pharmacokinetic characteristics of the scavenger receptors are poorly understood.
      In this review, we summarized basic findings on scavenger receptors reported in
      available literature, and introduced our recent studies on the quantitative
      characteristics of the scavenger receptor-mediated uptake. High molecular weight
      fractionated [3H]heparin (HMWFH, 16,000-24,000 Da), one of the model
      mucopolysaccharides, was investigated to elucidate its uptake mechanism into
      isolated rat Kupffer cells, isolated peritoneal macrophages and liver parenchymal
      cells in primary culture. The equilibrium bindings of HMWFH to isolated Kupffer
      cells and peritoneal macrophages were concentration-dependent with the respective
      dissociation constants (Kd) of 5.7 and 6.0 nM and with the respective maximum
      binding capacities (Bmax) of 1.5 and 1.9 pmol/10(6) cells. Several ligands of
      scavenger receptors inhibited the binding of HMWFH to macrophages, suggesting the
      involvement of scavenger receptors in the uptake of HMWFH by these macrophages.
      It was also suggested that the scavenger receptor-mediated uptake is different
      from the receptor-mediated endocytosis of polypeptides and phagocytosis, based on
      the evidence of the now inhibitory effects of an inhibitor of receptor-mediated
      endocytosis of polypeptides(phenylarsine oxide) and phagocytosis inhibitors
      (cytochalasine B and colchicine) on the internalization. The involvement of
      scavenger-like receptors was also suggested in the uptake of HMWFH by liver
      parenchymal cells in primary culture by demonstrating inhibitory effects of
      ligands for scavenger receptors. The internalization into liver parenchymal cells
      by scavenger-like receptors was not affected by an inhibitor of receptor-mediated
      endocytosis of polypeptides and phagocytosis inhibitors, similarly to the results
      in the macrophage scavenger receptors. The Kd of 53.5 nM and Bmax of 32.8
      pmol/10(6) cells in parenchymal cells were both in the order of magnitude larger
      than those in isolated Kupffer cells, suggesting the binding of HMWFH to
      scavenger-like receptors in parenchymal cells with lower affinity and higher
      capacity. On the other hand, an apparent internalization rate constant (kint,
      app) of 0.0056 min-1 was comparable with that in Kupffer cells (0.0118 min-1).
      Thus, we demonstrated the involvement of scavenger receptors in the uptake of
      HMWFH by rat Kupffer cells, peritoneal macrophages and liver parenchymal cells,
      and succeeded in characterizing the uptake kinetically. These findings should
      provide useful information for not only establishing the rational clinical use of
      mucopolysaccharides but also developing new drugs such as antiatherosclerotic
      agents and peptides delivered to cells with scavenger receptors.

PMID- 9513578
TI  - [Highly effective separation and highly sensitive detection for clinical
      chemistry and biochemistry].
AB  - Highly effective separation and highly sensitive detection reagents for clinical
      chemistry and biochemistry were developed and their applications were
      investigated. The sensitive detection of carboxylic acids was accomplished using
      9-anthryldiazomethane (ADAM) which gave intensely fluorescent derivatives from
      carboxylic acids without catalysts or heating. 1-Pyrenyldiazomethane was then
      synthesized and proved to react also readily with carboxylic acid and more
      sensitive than ADAM. The optical resolution of amino acid enantiomers was
      achieved using 2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyl isothiocyanate
      (GITC). GITC derivatized enantiomeric amino acids under mild conditions to give
      highly hydrophobic diastereomers which could be resolved on conventional reversed
      phase columns and easily detected by the absorption based on the thiourea
      structure. Then we devised an o-phthalaldehyde-N-acetylcystein reagent
      (OPA/NAcCys) giving diastereomers which were also resolved on a reversed phase
      column and detected fluorometrically with excellent sensitivity. OPA/NAcCys was
      useful for the assay of D-amino acids in the blood of uremic patients. The
      hypochlorite-thiamine method for the assay of proteins and peptides was
      established providing sensitive fluorometry, which well reflected the number of
      peptide groups in the molecule. This principle was applied to the assay using N
      chlorodansylamide, designed for the fluorometry of peptides. The alkaline
      ninhydrin method was applied to the detection of guanidino compounds in the blood
      of uremic patients. Several fluorometric methods for the simultaneous detection
      of reducing and non-reducing carbohydrates, and guanidines were found to be
      useful reagents for this purpose because these compounds were resistant to the
      oxidation with periodate. Then protamine-bound columns were prepared for the
      separation of carbohydrates on HPLC, which showed excellent recovery of reducing
      carbohydrates in comparison with conventional alkylamino columns.

PMID- 9513580
TI  - Who should take care of the child with asthma? The pediatrician or the allergist?

PMID- 9513581
TI  - Seasonal variation in the effects of major indoor and outdoor environmental
      variables on asthma.

PMID- 9513582
TI  - The effects of ipratropium bromide on histamine-induced bronchoconstriction in
      subjects with cervical spinal cord injury.
AB  - Previously, we reported that a majority of subjects with chronic cervical spinal
      cord injury (SCI) demonstrated airway hyperreactivity in response to inhaled
      methacholine. To further investigate mechanisms of airway hyperreactivity, 15
      male subjects with cervical SCI were challenged with aerosolized histamine, and
      on a separate day responders were rechallenged 30 min after the inhalation of 72
      micrograms of ipratropium bromide. Twelve of 15 subjects demonstrated airway
      hyperresponsiveness to histamine (geometric mean PC20 of 1.27 mg/ml), which was
      not blocked by pretreatment with ipratropium bromide (geometric mean PC20 1.50
      mg/ml). Baseline forced vital capacity and forced expiratory volume in 1 sec were
      not significantly different between responders and nonresponders (2.8 +/- 0.6 vs.
      3.0 +/- 0.4 L and 2.3 +/- 0.6 vs. 2.4 +/- 0.2 L, respectively). Findings that
      subjects with cervical SCI are hyperresponsive to methacholine and histamine,
      chemical agents with direct action through distinct receptor systems, suggest
      that bronchial hyperreactivity in these subjects represents a nonspecific process
      similar to that observed in patients with asthma.

PMID- 9513583
TI  - Effect of pranlukast, a leukotriene receptor antagonist, in patients with severe
      asthma refractory to corticosteroids.
AB  - We investigated the effect of pranlukast (ONO-1078), a cysteinyl leukotriene
      receptor antagonist, in 11 patients with severe bronchial asthma. The patients
      had been treated with 1600 micrograms/day of beclomethasone or 800-1600
      micrograms/day of beclomethasone plus 2.5-20 mg/day of prednisolone, but remained
      symptomatic. After a 2-week baseline period, the patients received 225 mg of
      pranlukast twice daily for 8 weeks. Morning and evening peak expiratory flow rate
      (PEF) and symptom scores (cough, dyspnea, sleep) were recorded in an asthma
      diary. Ten patients completed the study. Symptom scores, especially dyspnea and
      sleep scores, and the number of rescue beta 2-agonist inhalations were
      significantly decreased. The morning PEF significantly improved from a mean
      baseline value of 311 to 341 L/min by the end of the study period. The evening
      PEF also improved, from 328 to 348 L/min, although the difference was not
      significant. These results suggest that pranlukast may be effective in treating
      patients with severe asthma who are refractory to corticosteroid therapy.

PMID- 9513584
TI  - Parental perceptions of access to care and quality of care for inner-city
      children with asthma.
AB  - The objective of this study was to describe perceptions of asthma care,
      morbidity, and health service utilization by parents of children with asthma
      presenting to an inner-city emergency department (ED). A cross-sectional survey
      was conducted in an urban pediatric ED, with a convenience sample of 466 parents
      of children receiving asthma treatment during a consecutive 6-week period in late
      fall 1995. Parents completed a 30-item survey including sociodemographic data,
      source of primary medical care and asthma care for their child, selected measures
      of access to care, and medications used by their child in the week prior to the
      ED visit. Perceived quality of asthma care was measured by six items (summary
      score = 0-6) reported to have been performed by the child's asthma doctor:
      discussion of home peak flow monitoring, child-specific triggers, dogs/cats,
      smoke, postexacerbation calling instructions, and provision of a written asthma
      management plan. Functional morbidity was measured by nights of poor sleep, days
      of cough, and school days missed due to asthma in the previous month. Among 325
      patients with previously diagnosed asthma, 308 (97%) were reported to have a
      source of primary medical care. Of these, 126 respondents identified their
      primary care provider as the child's usual source of asthma care, while 158
      identified the ED as the usual source. The groups did not differ by insurance
      status, ethnicity, or mean age of the child. Thirty-nine percent of children with
      the same provider for primary and asthma care compared with 15% of children
      reported to receive their asthma care predominantly in the ED had used inhaled
      steroids or cromolyn in the week prior to the ED visit (p < .0001). Children with
      the same provider for primary and asthma care had a higher mean quality score
      than children receiving asthma care in the ED (3.7 vs. 2.8, p < 0.0001), but
      there was no relationship between source of asthma care and functional morbidity.
      The ED remains the usual source of asthma care for many inner-city children.
      Among parents surveyed in the ED, there was a significant relationship between
      source of usual asthma care and quality of care, but a relationship between usual
      source of asthma care and functional morbidity could not be identified.

PMID- 9513585
TI  - Effect of chronic antigen inhalation in guinea pigs.
AB  - To examine the role of airway inflammation in airway hyperresponsiveness (AHR),
      we examined the effect of chronic antigen inhalation in sensitized guinea pigs.
      Guinea pigs were actively sensitized with dinitrophenylated Ascaris suum extract
      (DNP-As) and repeatedly exposed to aerosolized DNP-As antigen once a day for 4 or
      10 days. Twenty-four hours after the last antigen exposure, airway responsiveness
      to inhaled acetylcholine (ACh) and bronchoalveolar lavage (BAL) were studied. The
      guinea pigs receiving 4 days of exposure to antigen demonstrated an increase in
      airway responsiveness to inhaled ACh (p < 0.05). On the other hand, the guinea
      pigs receiving 10 days of exposure to antigen showed no significant change in
      airway responsiveness to inhaled ACh. BAL fluid analysis indicated that a
      significant increase in the number of eosinophils and neutrophils was observed in
      both groups of guinea pigs. A significant increase in the number of lymphocytes
      in BAL fluid was observed in guinea pigs exposed for 10 days, but not in those
      exposed for 4 days. We conclude that repeated exposure to antigen induced both
      development and suppression of AHR. Our results suggest that airway inflammation
      may play a role in both the development and suppression of AHR.

PMID- 9513586
TI  - Multiple regression analysis of airway responsiveness in adult asthmatic
      patients.
AB  - The aim of this study was to determine which background variables exert the most
      influence on airway responsiveness in adult asthmatic patients. The relationships
      between airway response and background variables were investigated by multiple
      linear and logistic regression analysis in 97 asthmatic patients. Airway
      responsiveness was measured by the oscillation technique during methacholine
      inhalation challenge. The regression analyses revealed that modified Aas score
      "one of asthma severity score", was the major factor contributing to airway
      hyperreactivity. We conclude that the number of attacks during a previous year is
      the most important background factor related to airway hyperresponsiveness on a
      clinical basis.

PMID- 9513587
TI  - Effect of inhaled furosemide in acute asthma.
AB  - We assessed the acute bronchodilator effect of nebulized furosemide when added to
      conventional therapy of acute emergency department (ED) asthma. Using a double
      blind design, 42 patients with acute asthma were randomized to receive 2.5 mg
      nebulized salbutamol and either 40 mg of nebulized furosemide or saline solution.
      We recorded clinical variables (respiratory rate, heart rate, and pulsus
      paradoxus) and peak expiratory flow rates (PEFR) before and 15 and 30 min after
      therapy. We found no significant difference in PEFR between salbutamol/furosemide
      and salbutamol/saline-treated patients 15 and 30 min following inhalation. Other
      endpoints were equally unaffected. However, when we examined separately those
      patients whose exacerbations were of relative short duration (< 8 hr), PEFR
      improved significantly more in the furosemide-treated group. At 15 min, PEFR
      increased by 82 +/- 48% in the furosemide group compared to 35 +/- 40% in the
      control group (p = 0.03), an effect that was also evident at 30 min when PEFR had
      increased by 113 +/- 49% in the furosemide group versus 61 +/- 35% in the control
      group (p = 0.014). Respiratory rate, heart rate, and pulsus paradoxus improved
      with no differences between the groups. The beneficial effect of furosemide was
      not evident in patients who reported more prolonged duration (> 8 hr) of
      asthmatic symptoms. The response to furosemide appeared to be unrelated to
      concomitant ED therapy with corticosteroids, to baseline pulmonary function, or
      to patient demographic variables. We conclude that furosemide may offer additive
      bronchodilator benefits in acute naturally occurring asthma of relative short
      duration.

PMID- 9513588
TI  - Risk of readmission to hospital for pediatric asthma.
AB  - To describe risk for hospital readmission for pediatric asthma occurring within
      12 months of index hospital admission, we reviewed the medical records of all
      pediatric (age < 15 years) patients admitted for asthma to the Kaiser Foundation
      Hospital (KFH), Hayward, California, between September 30, 1991 and June 30,
      1993. Patients aged < 5 years or who had a history of prior hospital admission
      were at high risk for hospital readmission within 12 months of the index
      admission. A single-session asthma class did not reduce risk for hospital
      readmission.

PMID- 9513589
TI  - Response to pneumococcal immunization in children with and without recurrent
      infections.
AB  - Many children with recurrent sinopulmonary infections fail to mount an adequate
      humoral response following immunization with polysaccharide antigens. At present
      there are no controlled studies comparing responses to pneumococcal immunization
      in children with recurrent infections and a healthy, age-matched cohort.
      Immunological evaluation was performed on 66 children with recurrent
      sinopulmonary infections, aged 2-5 years (mean 3.06 +/- 0.92). A control group
      included 28 healthy, age-matched controls (mean 3.14 +/- 0.88 years). Both groups
      were immunized with 23 valent pneumococcal vaccine, and titers were measured
      before and 4 weeks after immunization. Antibody levels to 12 pneumococcal
      serotypes were measured via radioimmunoassay. Geometric preimmunization mean
      titers in the control group were 215.5 +/- 157 ngAbN/ml rising to 989.5 +/- 745
      ngAbN/ml compared to 77.71 +/- 38.4 ngAbN/ml increasing to 446.7 +/- 406 ngAbN/ml
      in the study group (p < .05). Serotypes 3, 4, 7F, 8, 9N, and 18C were the most
      immunogenic, while serotypes 6A and 14 were the least. Overall, the control group
      responded to 7.71 +/- 1.24 serotypes versus 5.1 +/- 2.0 in the study group (p <
      .05), where postimmunization titers at least doubled and rose to > or = 300
      ngAbN/ml. All controls responded to at least five or more serotypes, 26/28
      responded to 6 or more. In contrast, only 38/66 (57%) of study patients responded
      to five or more serotypes, and only 27/66 (41%) responded to at least 6 of 12.
      Preimmunization titers of greater than 300 ngAbN/ml were present in 30% (102/336)
      of the control serotypes; however, only 53 of these (52%) doubled post
      immunization; 22% of the elevated titers decreased post immunization. Markedly
      elevated titers > or = 500 ngAbN/ml were present in 20% (69/336) of the
      preimmunization serotypes, only 39% of these doubled post immunization. Twenty
      three valent pneumococcal vaccine is immunogenic in young, healthy children. A
      significant percentage of children with recurrent sinopulmonary infections fail
      to produce adequate serotype specific antibodies following pneumococcal
      immunization.

PMID- 9513590
TI  - Pharmacokinetic predisposition to nicotine from environmental tobacco smoke: a
      risk factor for pediatric asthma.
AB  - During the last decade several studies have shown that children whose parents
      smoke have higher rates of asthma. Recently, hair concentrations of cotinine have
      been shown to reflect systemic exposure to this constituent of smoke in both
      children and adults. At the present time it is not known, however, why some
      children exposed to passive smoking have asthma while others, similarly exposed,
      do not. The present study aimed at verifying whether asthmatic children are
      different from nonasthmatic children exposed to similar degrees of passive
      smoking in the way their bodies handle nicotine, a constituent of cigarette
      smoke. Seventy-eight asthmatic children were compared to 86 control children, all
      attending a consulting pediatric clinic in Toronto. A questionnaire completed by
      the parents and children detailed the daily number of cigarettes the child was
      exposed to and the identity of the smokers. Clinical data were extracted from the
      patients' charts. Urinary (corrected for creatinine) and hair concentrations of
      cotinine were measured by radioimmunoassays. The asthmatic and control children
      were of similar age, gender, and ethnic distribution, parental education, and
      socioeconomic status. Parents of asthmatic children tended to report a lower
      daily number of cigarettes (7.4 +/- 1.3/day vs. 11.2 +/- 2.3/day, p = 0.14), and
      this report agreed with the trend of urinary cotinine (47.1 +/- 9.1 ng/mg vs.
      62.6 +/- 11.5 ng/mg, respectively). Conversely, children with asthma had on
      average twofold higher concentrations of cotinine in their hair (0.696 +/- 0.742
      ng/mg) than control children (0.386 +/- 0.383) (p = 0.0001). In a similar manner,
      the hair:urine concentration ratio was significantly higher in children with
      asthma (0.028 +/- 0.002) than in their controls (0.18 +/- 0.003) (p = 0.0001).
      These results suggest that under exposure to similar amounts of nicotine,
      children with asthma have on average twofold higher systemic exposure to this
      constituent of cigarette smoke. These data suggest that out of all children
      passively exposed to environmental tobacco smoke, those who exhibit asthma have a
      higher systemic exposure to nicotine, possibly due to lower clearance rate. This
      is the first evidence of pharmacokinetic predisposition to environmental tobacco
      smoke as an etiological factor in pediatric asthma.

PMID- 9513591
TI  - The Asthma Outreach Project: a promising approach to comprehensive asthma
      management.
AB  - We describe a pilot system of coordinated asthma care emphasizing home visits by
      a community-based lay worker collaborating with a pediatrician, pharmacist, and
      public health nurse. Study participants included 23 low-income children with
      moderate to severe asthma and their families at an inner-city pediatric clinic.
      This system was successfully implemented, and client satisfaction was extremely
      high. Utilization review showed a reduction in hospitalizations, emergency
      department visits, and unscheduled clinic visits, and an increase in follow-up
      clinic visits. This model of care may reduce unscheduled service use and deserves
      further study as an alternative for asthma management among similar patient
      populations.

PMID- 9513592
TI  - (R)-3,N-dimethyl-N-[1-methyl-3-(4-methyl-piperidin-1-yl)
      propyl]benzenesulfonamide: the first selective 5-HT7 receptor antagonist.

PMID- 9513593
TI  - Novel antipsychotic agents with dopamine autoreceptor agonist properties:
      synthesis and pharmacology of 7-[4-(4-phenyl-1-piperazinyl)butoxy]-3,4-dihydro
      2(1H)-quinolinone derivatives.
AB  - To develop a novel antipsychotic agent which is an agonist of dopamine (DA)
      autoreceptors and an antagonist of postsynaptic DA receptors, a series of 7-[4-[4
      (substituted phenyl)-1-piperazinyl]butoxy]-3,4-dihydro-2 (1H)-quinolinones was
      synthesized and their dual activities were examined. The postsynaptic DA receptor
      antagonistic activities of the compounds were evaluated by their ability to
      inhibit stereotypy induced by apomorphine in mice, and the autoreceptor agonist
      activities were determined by their effects on the gamma-butyrolactone (GBL)
      induced increase in L-dihydroxyphenylalanine (DOPA) synthesis in the mouse brain.
      Many compounds inhibited the stereotypic behavior, and several compounds reversed
      the GBL-induced increase in the DOPA synthesis. Among them, 7-[4-[4-(2,3
      dichlorophenyl)-1-piperazinyl]-butoxy]-3,4-dihydro-2 (1H)-quinolinone (28,
      aripiprazole, OPC-14597) was found to have these two activities. This compound
      reversed the GBL-induced DOPA synthesis (ED50 values of 5.1 mumol/kg p.o.) and
      inhibited the APO induced stereotypy (ED50 values of 0.6 mumol/kg p.o.). Compound
      28 induced catalepsy at 10 times higher dose than that required for the
      antagonism of APO-induced stereotypy (ED50 value of 7.8 mumol/kg p.o.).

PMID- 9513594
TI  - Novel 3-aralkyl-7-(amino-substituted)-1,2,3-triazolo[4,5-d]pyrimidines with high
      affinity toward A1 adenosine receptors.
AB  - Three series of several 1,2,3-triazolo[4,5-d]pyrimidine derivatives bearing
      various amino substituents at the 7 position and one of three lipophilic
      substituents at the 3 position (benzyl, phenethyl, or 2-chlorobenzyl) were
      prepared starting from the corresponding 7-chloro compounds, by nucleophilic
      substitution by the appropriate amine. Radioligand binding assays at bovine brain
      adenosine A1 and A2A receptors showed that some compounds possessed a high
      affinity and selectivity for the A1 receptor subtype. In particular the
      biological results suggested the compounds bearing cycloalkylamino (cyclopentyl-
      and cyclohexylamino) or aralkylamino (alpha-methylbenzyl- and 1-methyl-2
      phenylethylamino or amphetamino) substituents at the 7 position were the most
      active derivatives. The best lipophilic substituent at the 3 position was the 2
      chlorobenzyl (A1 affinity Ki < 50 nM) followed by the benzyl and then the
      phenethyl groups. This pattern of structure-activity relationship (SAR) was
      similar to that previously reported for analogous 1,2,3-triazolopyridazino
      derivatives (Biagi et al., 1994, 1995, 1996) except for the compounds bearing
      substituted aromatic amines which presented a generalized and strong decrease of
      the A1 receptor affinity. These facts allowed us to attribute to these molecules
      a binding mode within the A1 adenosine receptor analogous to that of the
      corresponding triazolopyridazines.

PMID- 9513595
TI  - Mono- and disubstituted-3,8-diazabicyclo[3.2.1]octane derivatives as analgesics
      structurally related to epibatidine: synthesis, activity, and modeling.
AB  - A series of 3,8-diazabicyclo[3.2.1]octanes substituted either at the 3 position
      (compounds 1) or at the 8 position (compounds 2) by a chlorinated heteroaryl ring
      were synthesized, as potential analogues of the potent natural analgesic
      epibatidine. When tested in the hot plate assay, the majority of the compounds
      showed significant effects, the most interesting being the 3-(6-chloro-3
      pyridazinyl)-3,8-diazabicyclo[3.2.1]octane (1a). At a subcutaneous dose of 1
      mg/kg, 1a induced a significant increase in the pain threshold, its action
      lasting for about 45 min. 1a also demonstrated good protection at a dose of 5
      mg/kg in the mouse abdominal constriction test, while at 20 mg/kg it completely
      prevented the constrictions in the animals. Administration of naloxone (1 mg/kg
      i.p.) did not antagonize its antinociception while mecamylamine (2 mg/kg i.p.)
      did, thus suggesting the involvement of the nicotinic system in its action.
      Binding studies confirmed high affinity for the alpha 4 beta 2 nAChR subtype (Ki
      = 4.1 +/- 0.21 nM). nAChR functional activity studies on three different cell
      lines showed that 1a was devoid of any activity at the neuromuscular junction.
      Finally, due to the analogy in their pharmacological profile with that of
      epibatidine, compounds were compared from a structural and conformational point
      of view through theoretical calculations and high-field 1H NMR spectroscopy.
      Results indicate that all of them present one conformation similar to that of
      epibatidine.

PMID- 9513596
TI  - alpha-Substituted malonester amides: tools to define the relationship between
      ACAT inhibition and adrenal toxicity.
AB  - We prepared a series of alpha-substituted malonester amides that were evaluated
      for their ability to inhibit acyl-CoA:cholesterol O-acyl transferase activity in
      vitro and to lower plasma total cholesterol levels in a variety of cholesterol
      fed animal models. Compounds of this series were also useful in examining the
      relationship between adrenal toxicity and ACAT inhibition. One compound from this
      series, 9f, was a potent inhibitor of ACAT in both the microsomal and cellular
      assays. It was also bioavailable as determined by both a bioassay and a HPLC-UV
      assay. This compound was evaluated in both guinea pig and dog models of adrenal
      toxicity and compared to tetrazole amide 15. In the most sensitive species, the
      dog, both of these compounds achieved good plasma levels; however, compound 9f
      caused adrenal necrosis, whereas compound 15 had no effect on the adrenal gland.
      This adds to the growing body of evidence that the adrenal toxicity observed with
      ACAT inhibitors may not be mechanism related.

PMID- 9513597
TI  - A new method for predicting the alignment of flexible molecules and orienting
      them in a receptor cleft of known structure.
AB  - It is not always easy to align flexible compounds with each other or with their
      binding cleft on a biological macromolecule, and the alignment of nine partly
      flexible molecules has now been studied. These compounds are heme analogues
      having either two or three flexible propionate side chains attached to a
      porphyrin core, and one compound is a close analogue of natural heme. The
      noncovalent interactions of each compound were predicted using a new version of
      the program Grid which can take account of the flexibility of the propionate side
      chains. The Grid results were then analyzed by hierarchical principal component
      analysis, and this allowed the molecules to be oriented with respect to each
      other. It also allowed each analogue to be correctly aligned with the receptor
      cleft for heme in myoglobin, because the alignment of natural heme in that cleft
      is already known. Factors influencing the predicted alignment are also
      considered.

PMID- 9513598
TI  - Potent and selective ligands for the dopamine transporter (DAT): structure
      activity relationship studies of novel 4-[2-(diphenylmethoxy)ethyl]-1-(3
      phenylpropyl)piperidine analogues.
AB  - Molecular structural modifications of 4-[2-(diphenylmethoxy)ethyl]-1-(3
      phenylpropyl)piperidine (1a), a dopamine transporter (DAT)-specific ligand,
      generated several novel analogues. Biological activities of these new molecules
      for their binding to the DAT and serotonin transporter (SERT) were evaluated in
      rat striatal membranes. Some of these new analogues were more potent and
      selective than GBR 12909 when their binding to the DAT relative to SERT was
      compared. Thus compounds 9 and 19a were among the most potent (IC50 = 6.6 and 6.0
      nM, respectively) and selective (DAT/SERT = 33.8 and 30.0, respectively)
      compounds in this series, and they were more active than GBR 12909 (IC50 = 14 nM,
      DAT/SERT = 6.1). Introduction of a double bond in the N-propyl side chain of
      these molecules did not influence their activities to a great extent.
      Bioisosteric replacement of the aromatic phenyl group by a thiophene moiety
      produced some of the most potent compounds in this series.

PMID- 9513599
TI  - Discovery of novel pyridinopolyamines with potent antimicrobial activity:
      deconvolution of mixtures synthesized by solution-phase combinatorial chemistry.
AB  - A 1638-member pyridinopolyamine library, consisting of 13 sublibraries of 126
      members prepared by a solution-phase approach, was completely deconvoluted from
      orthogonally protected intermediates by a combination of iterative and positional
      scanning procedures. Antibacterial assays against Streptococcus pyogenes and
      Escherichia coli imp- and a Candida albicans yeast specificity assay were
      employed to follow the activity of sublibraries. Screening of the 13
      sublibraries, which were prepared by a synthetic method that places the
      differentiating functionality in a selected position A (secondary amine), at the
      end of the synthesis (fix last), provided several first-round activities.
      Subsequently, six single pyridinopolyamines (2-7) were prepared where the first
      round winner, a hydrogen atom, is in the first deconvoluted position and the
      remaining three positions contained the same functionalities. The range of
      antibacterial and yeast activities of these single compounds suggested that a
      more active and selective compound may be discovered by completely deconvoluting
      the first-round active sublibraries. Pyridinopolyamine positions B (secondary
      benzylamine) and C (primary benzylamine) were then sequentially positionally
      scanned with a set of six meta-substituted benzyl functionalities to generate two
      sets of second/third-round sublibraries, containing 21 or 36 compounds in each
      sublibrary, respectively. High-throughput screening yielded sublibraries 15, 18,
      and 21 with MICs of 1-5 microM against S. pyogenes and E. coli imp-. Using rounds
      1 and 2/3 screening data, two sets of single compounds (22-27) and (28-32) with
      the combination of m-(trifluoromethyl)-benzyl group at position C and m
      (trifluoromethyl)benzyl or m-methylbenzyl group at position B with position D
      (primary benzylamine) fixed were synthesized in the fourth round deconvolution.
      Subsequently, broader screening of deconvoluted compounds against a tier II panel
      of wild-type bacteria identified eight compounds (5, 7, 27, and 29-32) with
      approximately 100-fold greater selectivity for Gram-positive than Gram-negative
      bacteria. Thus, S. pyogenes, S. pyogenes (wild-type), Streptomyces aureus, and
      Enterococcus faecalis were inhibited at MICs of 1-12 microM, whereas MICs for E.
      coli, Klebsiella pneumoniae, Proteus vulgaris, and Pseudomonas aeruginosa were >
      100 microM. These eight compounds were not active (> 100 microM) against fungus
      C. albicans.

PMID- 9513600
TI  - Human growth hormone-releasing hormone hGHRH(1-29)-NH2: systematic structure
      activity relationship studies.
AB  - Two complete and two partial structure-activity relationship scans of the active
      fragment of human growth hormone-releasing hormone, [Nle27]-hGHRH(1-29)-NH2, have
      identified potent agonists in vitro. Single-point replacement of each amino acid
      by alanine led to the identification of [Ala8]-, [Ala9]-, [Ala15]- (Felix et al.
      Peptides 1986 1986, 481), [Ala22]-, and [Ala28, Nle27]-hGHRH(1-29)-NH2 as being 2
      6 times more potent than hGHRH(1-40)-OH (standard) in vitro. Nearly complete loss
      of potency was seen for [Ala1], [Ala3], [Ala5], [Ala6], [Ala10], [Ala11],
      [Ala13], [Ala14], and [Ala23], whereas [Ala16], [Ala18], [Ala24], [Ala25],
      [Ala26], and [Ala29] yielded equipotent analogues and [Ala7], [Ala12], [Ala17],
      [Ala20], [Ala21], and [Ala27] gave weak agonists with potencies 15-40% that of
      the standard. The multiple-alanine-substituted peptides [MeTyr1,Ala15,22,Nle27]
      hGHRH(1-29)-NH2 (29) and [MeTyr1,Ala8,9,15,22,28,Nle 27]-hGHRH(1-29)-NH2 (30)
      released growth hormone 26 and 11 times, respectively, more effectively than the
      standard in vitro. Individual substitution of the nine most potent peptides
      identified from the Ala series with the helix promoter alpha-aminoisobutyric acid
      (Aib) produced similar results, except for [Aib8] (doubling vs [Ala8]), [Aib9]
      (having vs [Ala9]), and [Aib15] (10-fold decrease vs [Ala15]). A series of cyclic
      analogues was synthesized having the general formula cyclo(25-29)[MeTyr1,
      Ala15,Xaa25,Nle27,Yaa29+ ++]-GHRH(1-29)-NH2, where Xaa and Yaa represent the
      bridgehead residues of a side-chain cystine or [i-(i + 4)] lactam ring. The ring
      size, bridgehead amino acid chirality, and side-chain amide bond location were
      varied in this partial series in an attempt to maximize potency. Application of
      lactam constraints in the C-terminus of GHRH(1-29)-NH2 identified cyclo(25
      29)[MeTyr1,Ala15,DAsp25,Nle27,Orn29+ ++]-hGHRH(1-29)-NH2 (46) as containing the
      optimum bridging element (19-membered ring) in this region of the molecule. This
      analogue (46) was 17 times more potent than the standard. Equally effective was
      an [i-(i + 3)] constraint yielding the 18-membered ring cyclo(25
      28)[MeTyr1,Ala15,Glu25,Nle,27Lys28]- hGHRH-(1-29)-NH2 (51) which was 14 times
      more potent than the standard. A complete [i-(i + 3)] scan of cyclo(i,i +
      3)[MeTyr1,Ala15,Glui,Lys(i + 3),Nle27]-hGHRH(1-29)-NH2 was then produced in order
      to test the effects of a Glu-to-Lys lactam bridge at all points in the peptide.
      Of the 26 analogues in the series, 11 had diminished potencies of less than 10%
      that of the agonist standard, 4 were weak agonists (15-40% relative potency), and
      4 analogues were equipotent to the standard. The 7 most potent analogues ranged
      in potency from 3 to 14 times greater than that of the standard and contained the
      [i-(i + 3)] cycles between residues 4-7, 5-8, 9-12, 16-19, 21-24, 22-25, and 25
      28. The combined results from these systematic studies allowed for an analysis of
      structural features in the native peptide that are important for receptor
      activation. Reinforcement of the characteristics of amphiphilicity, helicity, and
      peptide dipolar effects, using recognized medicinal chemistry approaches
      including introduction of conformational constraints, has resulted in several
      potent GHRH analogues.

PMID- 9513601
TI  - Novel potent and selective central 5-HT3 receptor ligands provided with different
      intrinsic efficacy. 1. Mapping the central 5-HT3 receptor binding site by
      arylpiperazine derivatives.
AB  - Synthesis and pharmacological evaluation of a series of condensed quinoline and
      pyridine derivatives bearing a N-methylpiperazine moiety attached to the 2
      position of the quinoline or pyridine nucleus are described. 5-HT receptor
      binding studies revealed subnanomolar affinity for the 5-HT3 receptor subtype in
      some of the compounds under study. The most active compound (5b) displayed a Ki
      value about 1 order of magnitude higher than that of quipazine along with a
      higher selectivity. The potential 5-HT3 agonist/antagonist activity of four
      selected compounds was assessed in vitro on 5-HT3 receptor-dependent
      [14C]guanidinium uptake in NG 108-15 cells. Compound 5j acted as a 5-HT3 agonist
      in this assay with an EC50 value close to that reported for quipazine, while 5b
      was a partial agonist with an EC50 value of about 0.25 nM, and compound 5c
      possessed antagonist properties with an IC50 value (approximately 8 nM) in the
      same range as those of previously characterized 5-HT3 receptor antagonists.
      Qualitative and quantitative structure-affinity relationship studies carried out
      by making use of theoretical molecular descriptors allowed to elucidate the role
      of the main pharmacophoric components and to develop a model for the interaction
      of the 5-HT3 ligands related to quipazine with their receptor.

PMID- 9513602
TI  - Tyrosine kinase inhibitors. 14. Structure-activity relationships for methylamino
      substituted derivatives of 4-[(3-bromophenyl)amino]-6-(methylamino)-pyrido[3,4
      d]pyrimidine (PD 158780), a potent and specific inhibitor of the tyrosine kinase
      activity of receptors for the EGF family of growth factors.
AB  - The 4-[(3-bromophenyl)amino]pyrido[3,4-d]pyrimidine PD 158780 is a very potent in
      vitro inhibitor of the tyrosine kinase activity of the epidermal growth factor
      receptor (EGFR) (IC50 0.08 nM), and other members of the erbB family, by
      competitive binding at the ATP site of these signal transduction enzymes. A
      series of analogues of PD 158780 bearing solubilizing functions off the 6
      methylamino substituent were prepared by reaction of the 6-fluoro derivatives
      with appropriate amine nucleophiles. These were evaluated for their ability to
      inhibit the tyrosine phosphorylating action of EGF-stimulated full-length EGFR
      enzyme and for inhibition of autophosphorylation of the EGFR in A431 human
      epidermoid carcinoma cells in culture. The most effective analogues were those
      bearing weakly basic substituents through a secondary amine linkage, which proved
      water-soluble (> 10 mM) and potent (IC50S generally < 1 nM). No clear SAR could
      be discerned for these compounds with respect to amine base strength or the
      distance of the cationic center from the chromophore, suggesting that 6
      substituents are in a favorable area of bulk tolerance in the enzyme binding
      site. More distinct SAR emerged for the ability of the compounds to inhibit EGFR
      autophosphorylation in A431 cells, where analogues bearing lipophilic weak bases
      were preferred. Representative analogues were evaluated for antitumor
      effectiveness against four in vivo tumor models. Significant in vivo activity was
      observed in estrogen-dependent MCF-7 breast and A431 epidermoid tumors. Marginal
      activity was seen in an EGFR-transfected tumor model, suggesting that while this
      cell line requires EGF for clone formation in soft agar, other growth factors may
      be able to replace EGF in vivo. Also, no activity was seen against the SK-OV-3
      ovarian cancer model, which is known to express other EGF receptor family members
      (although it is not clear whether these are absolutely required for growth in
      vivo). While substantial growth delays were seen in A431 and MCF-7 tumor models,
      the treated tumors remained approximately the same size throughout therapy,
      suggesting that the compounds are cytostatic rather than cytotoxic under these
      test conditions. It remains to be determined if more prolonged therapy has
      cytotoxic effects in vivo, resulting in net tumor cell kill.

PMID- 9513603
TI  - Synthesis of C3 heteroatom-substituted azetidinones that display potent
      cholesterol absorption inhibitory activity.
AB  - The C3 phenylpropyl side chain of N-phenylazetidinones related to SCH 56524 was
      modified by replacing the hydroxymethylene with various isoelectronic or
      isosteric groups. Modifications at the 3' position led to less-active compounds;
      however, modifications at the 1' position provided compounds with improved
      cholesterol absorption inhibitory activity. An enantioselective route for the
      synthesis of C3 1'-sulfur-substituted azetidinones and the development of
      structure-activity relationships for this series of compounds are presented.

PMID- 9513605
TI  - Accountability of physicians in France.

PMID- 9513606
TI  - Acetaminophen-codeine combinations for rheumatic disorders.

PMID- 9513607
TI  - Anticentromere antibodies in rheumatologic practice are not consistently
      associated with scleroderma.
AB  - Anticentromere antibodies identified by indirect immunofluorescence are a
      valuable aid to the diagnosis and prognosis of patients with systemic sclerosis
      since they are associated in 50% to 80% of cases with limited cutaneous systemic
      sclerosis, a pattern usually associated with a good prognosis. We studied
      clinical presentations in rheumatology patients with anticentromere antibodies by
      indirect immunofluoresence and by ELISA and/or Western blot, but without
      scleroderma or Raynaud's phenomenon. Eight of 34 (23.5%) rheumatology clinic
      patients with centromere antibodies met these criteria, seven women and one man,
      with a median symptom duration of six years (range 1-20 years). Four had
      Sjogren's syndrome, one had isolated xerostomia, one systemic lupus
      erythematosus, one seronegative symmetric polyarthritis and one primary biliary
      cirrhosis with arthralgia. The mean anticentromere antibody titer in these eight
      patients was similar to that in the patients who had at least Raynaud's
      phenomenon. Given the low incidence of scleroderma, these data illustrate the
      poor predictive value of anticentromere antibodies for the diagnosis of
      scleroderma in rheumatology clinic patients.

PMID- 9513604
TI  - Aminopyrimidines with high affinity for both serotonin and dopamine receptors.
AB  - A series of [4-[2(4-arylpiperazin-1-yl)alkyl]cyclohexyl]pyrimidin-2-ylamine s was
      prepared and found to have receptor binding affinity for D2 and D3 dopamine (DA)
      receptors and serotonin 5-HT1A receptors. The structural contributions to D2/D3
      and 5-HT1A receptor binding of the aminopyrimidine, cycloalkyl, and
      phenylpiperazine portions of the molecule were examined. From these studies
      compounds 14, 39, 42, 43, having potent affinity for both DA D2 and 5-HT1A
      receptors, were evaluated for intrinsic activity at these receptors, in vitro and
      in vivo. Compound 14 (PD 158771) had a profile indicative of partial agonist
      activity at both D2 and 5-HT1A receptors causing partially decreased synthesis of
      the neurotransmitters DA and 5-HT and their metabolites. This compound has a
      profile in behavioral tests that is predictive of antipsychotic activity,
      suggesting that mixed partial agonists such as 14 may have utility as
      antipsychotic agents with increased efficacy and decreased side effects.

PMID- 9513608
TI  - CENP-B autoantigen is a conserved protein from humans to higher plants:
      identification of the aminoterminal domain in Phaseolus vulgaris.
AB  - Centromeres are critical structures in cell division, and CENP-B is the most
      important protein of the centromeric complex recognized by autoantibodies from
      patients with scleroderma. Our major aim was to demonstrate whether CENP-B is a
      conserved protein along the phylogenic scale including the higher plants. Vegetal
      and human cell proteins were extracted from Phaseolus vulgaris and HEp-2 cells
      and were characterized by PAGE, Western blot, and human autoimmune sera
      containing anti-CENP-B autoantibodies. The aminoterminus of the gene encoding for
      CENP-B from HEp-2 cells and Phaseolus vulgaris was isolated by reverse
      transcriptase-PCR using complementary oligonucleotides to the human CENP-B gene.
      Also, in situ hybridization was performed on vegetal tissues and HEp-2 cells
      using human CENP-B box probes. Our main results were as follows: 1) Autoimmune
      sera were reactive to a vegetal protein of 80 kDa. 2) Affinity-purified anti-CENP
      B antibodies recognized a protein from Phaseolus vulgaris with molecular mass
      similar to that found in human cells. Vegetal and HEp-2 cells CENP-B proteins
      were immunologically identical. 3) Using RT-PCR, we were able to amplify a cDNA
      encoding for the aminoterminus domain of CENP-B from Phaseolus vulgaris that had
      the same molecular behaviour as the cDNA from HEp-2 cells. 4) Complementary
      oligonucleotides for human CENP-B box hybridized a DNA sequence from Phaseolus
      vulgaris. In conclusion, CENP-B protein is a conserved protein along the
      phylogenic scale from humans to higher plants.

PMID- 9513609
TI  - A study of metalloproteinases in fifty joint fluid specimens.
AB  - OBJECTIVES: To study the activity and concentrations in joint fluid of
      gelatinases (A or matrix metalloproteinase (MMP)-2 and B or MMP-9), tissue
      inhibitor of metalloproteinases 1 (TIMP-1), and stromelysin-1 (MMP-3). METHODS:
      Synovial fluid specimens obtained as part of a diagnostic or therapeutic
      procedure were studied. Protein levels were determined, cells counted, crystals
      looked for and microbiological studies done. Gelatinolytic activity was
      determined quantitatively using computerized zymography. Proteins were identified
      by electrotransfer and immunorevelation. TIMP-1 and stromelysin-1 were assayed
      using an ELISA. Results were confronted with laboratory test and clinical
      findings. RESULTS: Of the 50 specimens studied, 25 were from joints with
      mechanical disorders and 25 from joints with inflammatory disorders. Activated
      MMP-2 was found in all the specimens, with no differences between the two groups.
      MMP-9 was found only in its inactive form. MMP-9, TIMP-1 and MMP-3 were found
      more often in inflammatory than in mechanical fluids and the levels of MMP-9 and
      TIMP-1 were correlated with neutrophil counts. In the 16 fluids from rheumatoid
      arthritis patients, levels of MMP-9 and TIMP-1 were closely correlated with serum
      C-reactive protein levels. CONCLUSIONS: MMP-9, TIMP-1, and MMP-3 levels show
      striking differences between inflammatory and mechanical joint fluids.

PMID- 9513610
TI  - No link between avascular necrosis of the femoral head and antiphospholipid
      antibodies.
AB  - The rate of occurrence of antiphospholipid antibodies was compared in 47 patients
      with avascular necrosis of the femoral head and in 47 controls matched on age and
      sex. Antiphospholipid antibodies were looked for using three techniques in each
      patient, namely the VDRL test, an ELISA for anticardiolipin, and a circulating
      anticoagulant detection procedure involving three different tests. The VDRL and
      the tests for circulating anticoagulants were negative in all the patients and
      controls. No significant between-group difference was found for the ELISA, which
      was positive in three patients and two controls.

PMID- 9513611
TI  - Septic arthritis of lumbar facet joints. A review of six cases.
AB  - Hematogenous infection of the facet joints by pyogenic organisms is exceedingly
      rare. We report six cases of lumbar facet joint septic arthritis due to
      hematogenous spread of a pyogenic organism. A review of the literature identified
      ten anecdotal reports of similar cases. An analysis of these 16 cases showed that
      the diagnosis was based mainly on imaging study findings and that clinical data
      failed to discriminate between facet joint septic arthritis and infectious
      discitis. Increased uptake on the radionuclide bone scan was an early finding and
      the pattern of uptake was different from that seen in discitis. Computed
      tomography was the investigation that best delineated the facet joint lesions.
      Magnetic resonance imaging of the lumbar spine was superior over computed
      tomography in demonstrating spread of the infection to the epidural space and/or
      soft tissues and in some instances demonstrated enhancement of the infected facet
      joint on T1 images after gadolinium injection. Aspiration of the facet joint
      under fluoroscopic guidance was required only when blood cultures were negative
      or when the diagnosis of the septic nature of the arthritis was in doubt. Blood
      cultures yielded a Staphylococcus aureus in the six cases in our series.
      Appropriate antimicrobial therapy was successful in most cases. In our series,
      four of the six patients had posterior epiduritis, pyomyositis, or an abscess in
      the paraspinal muscles or psoas muscle, suggesting that some epidural infections
      or psoas muscle abscesses believed heretofore to be primary may in fact be
      complications of facet joint septic arthritis. Facet joint septic arthritis is a
      new aspect of pyogenic spinal infections that deserves to be considered in
      patients with febrile spinal syndromes not explained by discitis.

PMID- 9513612
TI  - Osteoarthritis of the pisiform-triquetral compartment. A review of eight cases of
      an underrecognized entity.
AB  - Seven patients (eight hands) with pain suggestive of the pisiform-triquetral
      compartment were studied to compare outcomes after surgical excision of the
      pisiform (four hands) and after conservative therapy (four hands). All patients
      were reevaluated by a rheumatologist who was not involved in their treatment. The
      efficacy of conservative therapy was mediocre in every case. Although it is
      reasonable to assume that the surgically-treated patients had more severe
      manifestations at baseline, all were free of symptoms at reevaluation, versus
      none of the conservatively-treated patients. After two years, excision of the
      pisiform yielded excellent results with no adverse effects on range of motion or
      grip strength. Despite the small size of our sample and the relatively low
      incidence of pisitriquetral osteoarthritis, our data suggest that surgery is
      preferable over conservative therapy in this condition.

PMID- 9513613
TI  - Estrogen therapy in postmenopausal osteoporosis. What we know and what we don't.
AB  - Replacement estrogen therapy is of proven efficacy for the prevention and
      treatment of postmenopausal bone loss. Oral and transdermal 17 beta estradiol
      have provided similar benefits in clinical studies. The lowest effective doses
      are 0.625 mg per day for conjugated estrogens, 2 mg per day for oral 17 beta
      estradiol, 1.5 micrograms per day for 17 beta estradiol gel, and 50-microgram 17
      beta estradiol patch per day. Bone mineral density should be monitored if lower
      doses are used. Several epidemiologic studies found that a decrease in the
      incidence of osteoporotic fractures was achieved only when the duration of
      estrogen replacement therapy exceeded seven years. It follows that replacement
      therapy should be started at cessation of menses, if possible. However delayed
      replacement therapy (i.e., at 65 years of age) is unquestionably effective.

PMID- 9513614
TI  - Specific features of immunoglobulin D multiple myeloma.

PMID- 9513615
TI  - Vasculitis confined to the calves. Report of a case.
AB  - Polyarteritis nodosa is a systemic disease of which limited forms have been
      reported, with the most common involving the skin. Only 13 cases with lesions
      confined to the calves have been reported to date. We report a new case.

PMID- 9513616
TI  - Spontaneous epidural hematoma discovered upon evaluation of a calcified disk
      herniation.
AB  - A female renal transplant recipient had intractable femoral neuralgia due to a
      large calcified disk herniation. She then developed an anterior epidural hematoma
      above the herniation, from T12 to L2, in the absence of clotting disorders.
      Spontaneous resorption of the hematoma occurred. The femoral neuralgia resolved
      after surgical treatment of the herniation. The location of the hematoma suggests
      that the calcified disk may have torn the fragilized epidural venous network.

PMID- 9513617
TI  - Enalapril-induced vasculitis resembling rheumatoid arthritis, lupus, sicca
      syndrome, and giant cell arteritis.
AB  - We report a case of vasculitis in a 67-year-old woman who successively developed
      over a four-month period clinical manifestations suggestive of rheumatoid
      arthritis, lupus, sicca, syndrome and finally giant cell arteritis. All her
      symptoms resolved promptly upon discontinuation of enalapril and none recurred
      over the five-year follow-up period. The only residual manifestation is Jaccoud's
      arthropathy of the hands.

PMID- 9513618
TI  - Is SAPHO syndrome a spondylarthropathy? A vasculopathy? Report of a case.
AB  - We describe the case of a patient who had SAPHO syndrome with mediastinal and
      retroperitoneal fibrosis. After several years, he developed erosive polyarthritis
      and systemic vasculopathy. The possible implications of these associations are
      discussed.

PMID- 9513619
TI  - Rheumatic manifestations of scurvy. A report of two cases.
AB  - Bleeding into the muscles and joints can be the presenting manifestation of
      scurvy, as illustrated by two case-reports. One patient presented with
      hemarthrosis of the tibiotalar joint due to an insufficiency fracture and was
      suspected to have scurvy based on the presence of purpura and hypertrophy of the
      gums with loss of teeth. In the other patient, multiple hematomas in the lower
      limbs were found at presentation and the presence of coiled hairs suggested the
      diagnosis. Both patients had completely eliminated fruit and vegetables from
      their diet. Low levels of ascorbic acid were found in serum and urine. A full
      recovery was achieved in both cases under ascorbic acid supplementation.

PMID- 9513620
TI  - Tendinitis of the tibialis anterior with histologic documentation in a patient
      under fluoroquinolone therapy.

PMID- 9513621
TI  - Recurrent posttraumatic hematoma leading to discovery of a muscle metastasis.

PMID- 9513622
TI  - Posttraumatic diffuse eosinophilic fasciitis accepted for workers' compensation.

PMID- 9513623
TI  - Hyperthyroidism due to iodide contained in a colchicine preparation.

PMID- 9513624
TI  - A prospective study of pulmonary symptoms in 188 patients with rheumatoid
      arthritis.

PMID- 9513625
TI  - Anterior chest wall involvement in psoriatic arthritis.

PMID- 9513626
TI  - Survey assessment of methadone treatment services as reinforcers.
AB  - Offering incentives contingent on behavioral change can be an effective method
      for improving treatment outcome in methadone maintenance. Further, there are
      several incentives available within the daily operation of methadone clinics that
      can be used in this way. This study describes patient preferences for clinic
      service incentives as identified by three types of survey methodologies: multiple
      choice procedures, visual analog scales, and rank ordering. Methadone patients (n
      = 111) rated preference for three service incentives (take-home medication, dose
      increase, counseling sessions) using each survey. Mean and individual responses
      were highly consistent across surveys and indicated that, in general, take-homes
      were the most preferred, followed by dose increases and then counseling. The rank
      order survey also assessed an additional 18 service items (e.g., rent, food or
      gas payments; employment assistance; medical care). Consistent with other
      measures, most patients (64%) placed take-homes within their top five rankings,
      indicating a high level of preference, but this survey also revealed wide
      individual differences in preference ranking. The surveys described can be used
      to identify preferred incentives for clinic-wide use in contingency management
      programs or can be used to select individualized incentives for each patient.
      This is useful information for maximizing utilization of clinic resources.

PMID- 9513628
TI  - Increasing participation in substance abuse aftercare treatment.
AB  - Increasing the length of participation in alcohol and drug treatment is
      associated with improved outcomes (1). The present study was designed to increase
      substance abuse aftercare participation following completion of inpatient
      treatment. We compared the effect of a 20-minute aftercare orientation session to
      a minimal treatment condition on aftercare group therapy participation. The
      orientation session was conducted by an aftercare group therapist, who met with
      the participant to encourage him to attend aftercare, to explain why aftercare is
      helpful, and to have him sign an aftercare participation contract. Participants
      in the minimal treatment condition watched a videotape on motivation to reach
      goals. Participants were 40 males in an inpatient substance abuse treatment
      program at a Veterans Affairs Medical Center (VAMC). Ninety percent were alcohol
      dependent; 35% were cocaine dependent; 10% were marijuana dependent; and 10% were
      polysubstance dependent. Participants who received the aftercare orientation were
      more likely to attend aftercare (70%) than those who received the minimal
      treatment (40%). Additionally, the former group attended more sessions (x = 3.0)
      than those who were not oriented to aftercare (x = 1.4). The utility and
      limitations of a brief orientation session on aftercare adherence are discussed.

PMID- 9513627
TI  - Community reinforcement approach in the treatment of opiate addicts.
AB  - The authors studied the efficacy of the community reinforcement approach (CRA) as
      compared to standard counseling in opiate-dependent patients on methadone
      maintenance. One hundred eighty subjects were randomized to three treatment
      conditions: standard, CRA, and CRA with relapse prevention (CRA/RP). Of these,
      151 subjects were followed up 6 months after intake. Since few of the RP sessions
      had been concluded at the 6-month follow-up, the two CRA groups were combined for
      analyses. Weekly urinalysis drug screens and Addiction Severity Index (ASI)
      scores at intake and 6 months were compared. The combined CRA groups did
      significantly better than the standard group in the following areas: consecutive
      opiate-negative urinalysis (3 weeks), and the 6-month ASI drug composite score.
      These results support the benefit of adding CRA strategies to the treatment of
      patients who are opiate dependent and on methadone maintenance. Because of
      insufficient treatment exposure to RP at the 6-month follow-up, the additive
      effect of RP could not be adequately evaluated; further follow-up will be
      required.

PMID- 9513629
TI  - The family experiences of narcotic addicts and their subsequent parenting
      practices.
AB  - This survey study of male and female narcotic addicts participating in methadone
      maintenance programs examined self-reported retrospective data on parental
      behavior experienced by addicts during their adolescent years. These findings
      were contrasted with the addicts' self-report of their current parenting
      practices with their own adolescent children. Results showed addicts as
      perceiving their mothers as significantly more functional in their parenting
      practices than their fathers on indices of parental involvement, attachment, and
      responsibility. Significant parenting differences between addicts and their
      parents were reported for the three indices mentioned, as well as for parent
      discipline and punitive actions, with the addicts rating their current parenting
      practices as more effective than those of their parents. Reported parenting
      practices were further analyzed in the context of how the ratings of parental
      functioning were related to problems of drug and alcohol abuse exhibited in the
      home. Findings are discussed in terms of the implications for prevention and
      treatment approaches for addicts and their children.

PMID- 9513630
TI  - Family variables in substance-misusing male adolescents: the importance of
      maternal disorder.
AB  - Selected family variables, especially maternal behaviors, were studied as
      predictors of alcohol and drug misuse in severely disturbed adolescent boys from
      largely father-absent homes. The families of 50 male youths (mean age 15.8 years)
      in a residential center for alcohol and substance misuse were compared with the
      families of a community control group (mean age 16.3 years). Within-subject group
      comparisons also were made. Family structure, interactive processes, maternal and
      paternal alcohol and substance use, and criminality were assessed through direct
      interview and/or self-report. The families of alcohol- and substance-misusing
      boys were markedly disadvantaged or impaired on numerous family structure,
      process, and substance-misusing behavioral variables in comparison with community
      controls. Within the alcohol- and substance-misusing group itself, family process
      variables, maternal alcohol symptoms, and maternal criminality differentiated
      boys with more vs. less severe drug-dependence symptoms. Maternal alcohol
      problems and criminality were more important than family process variables.
      Paternal alcohol or substance misuse or criminality did not differentiate proband
      symptom severity. We concluded that maternal alcohol symptoms and criminality
      differentiate severity of drug dependence in severely disturbed, substance
      misusing adolescent males from largely father-absent homes. Maternal substance
      misuse should be evaluated carefully in adolescent substance abuse treatment
      settings.

PMID- 9513632
TI  - Drug abuse--related mortality in the United States: patterns and correlates.
AB  - This study examines the sociodemographic determinants of psychoactive drug
      related mortality in the United States, using data from the National Health
      Interview Survey (1987-1990 combined) linked with National Death Index data
      (deaths through 1991). Proportional hazards models are used to estimate the gross
      and net effects of age, sex, race, marital status, education, income, employment
      status, and health status on the risk of drug-related mortality. Results show
      that age, sex, and race (the main breakdowns in previous studies), as well as
      marital status, income, and health status have significant net effects on the
      risk of drug-related mortality.

PMID- 9513631
TI  - A preliminary investigation of lamotrigine for cocaine abuse in HIV-seropositive
      patients.
AB  - Theoretical considerations as well as pre-clinical data suggest a potential role
      for glutamate-inhibiting agents in the treatment of cocaine addiction. At
      present, however, there is little clinical data to inform the use of these agents
      for this application. In this preliminary study eighteen HIV-seropositive cocaine
      dependent, opiate-agonist maintained patients received lamotrigine (300 mg/day),
      an indirect glutamate release inhibitor, on either a standard (n = 8) or
      accelerated (n = 10) induction schedule for 12 weeks. Results showed a
      significant decrease in percentage of cocaine-positive urine screens in the
      standard induction lamotrigine group but not in the accelerated induction group.
      There were fewer reports of side-effects and fewer dropouts in the standard
      induction lamotrigine group compared to the accelerated induction group.
      Neuropsychological assessments suggested a decrement in the Trail Making Tests,
      but no other decreases in cognitive functioning. We conclude that standard
      induction lamotrigine warrants further investigation for the treatment of cocaine
      abuse in this patient population.

PMID- 9513633
TI  - The association of personality characteristics with parenting problems among
      alcoholic couples.
AB  - This retrospective cross-sectional study explored the associations of personality
      characteristics with parenting problems among 25 couples, one or both members of
      which were identified as alcoholics by virtue of their voluntary past completion
      of a residential program for alcoholics. Most of them (90%) scored lower,
      indicating their more problematic parental attitudes and behaviors, on all four
      scales of the Adult-Adolescent Parenting Inventory (AAPI: inappropriate parental
      expectations of children, lack empathy for children's needs, value physical
      punishment, and parent-child role reversal) than average "normal" nonalcoholic,
      nonabusive adults. Such parenting problems were found to be very highly
      associated with clients' personality characteristics. For example, schizoid,
      schizotypal, histrionic, and passive aggressive characteristics (DSM-III-R-based)
      along with a few other personal characteristics of the couples, accounted for
      nearly all (90.2%, R2 = .902) of their propensity to reverse roles with their
      children. Findings also suggested that the identified parenting problems among
      alcoholic couples are amenable to programmatic intervention: the longer couples
      had participated in aftercare programs offered by the treatment facility the more
      appropriate and empathetic was their parenting.

PMID- 9513634
TI  - Children's beliefs about drinking.
AB  - This paper reports the results of a study in which age (grade level),
      racial/ethnic, and gender differences in beliefs and perceived norms about
      drinking were examined in a multi-ethnic urban sample of 4th through 7th grade
      children. Results showed that older children held beliefs and perceived norms
      that were more favorable toward drinking than younger children. The major
      difference between older and younger children lay in their differential estimates
      of the likelihood of certain consequences occurring and not in their evaluation
      of these consequences of drinking. Further, older children not only displayed
      less motivation to comply with their parents and greater motivation to comply
      with their peers, but they also perceived their parents, as well as their peers,
      as less disapproving of drinking than did younger children. There were few gender
      or race/ethnicity differences at these ages in children's beliefs and perceived
      norms about drinking.

PMID- 9513636
TI  - Validation of the criteria for DSM diagnosis of cocaine abuse and cocaine
      dependence.
AB  - The concurrent external validity of the diagnosis of cocaine abuse, based on the
      DSM criteria, is shown to be established to an unexpectedly high degree, based on
      a method of determining the association between a summary score derived by
      quantifying the DSM criteria and another summary score derived from weighting
      several measures of frequency of use of cocaine and a measure of its mode of use.
      The degree of validity was cross-validated by performing the same analysis on two
      study samples: one of inpatients (N = 179) and one of urban-community African
      Americans (N = 204).

PMID- 9513635
TI  - Mixed psychosocial outcomes of sisters from families with alcoholic parents.
AB  - To examine intrafamilial differences in adulthood among children of alcoholic
      parents, 14 women with alcoholic parents and their sisters were assessed for this
      exploratory study. Reported here is the subset of eight "mixed" sister pairs, one
      with an impaired adult outcome and the other with a well-adjusted adult outcome.
      Subjects who scored significantly worse than community norms on depressed mood or
      social supports or who had a psychiatric diagnosis including substance abuse were
      categorized as impaired, while the remaining women were categorized as well
      adjusted. Both qualitative and quantitative data were collected using a
      questionnaire and a structured interview. Results showed similarities between the
      impaired and well-adjusted sisters on individual characteristics, with few
      differences on characteristics of the parental alcoholism. The most marked
      differences showed the impaired sisters to score worse than their well-adjusted
      sisters on characteristics of the home environment and social supports. The
      impaired women were also more likely to have been physically abused in childhood
      and to rate the effect of having an alcoholic parent as more negative than the
      well-adjusted women. Unanticipated findings relating to incest, talents, denial,
      and racial differences, and their implications for clinicians and researchers,
      are discussed.

PMID- 9513637
TI  - GHB-induced delirium: a case report and review of the literature of gamma
      hydroxybutyric acid.
AB  - We describe what we believe is the first psychiatric hospitalization due to GHB
      induced delirium reported in the medical literature. We examine the use of the
      substance gamma hydroxybutyric acid (GHB) and describe the clinical findings in a
      patient who presented to an acute inpatient psychiatric unit with a chief
      complaint of feeling suicidal and a 1-year history of GHB use. A review of the
      literature and GHB's availability through the Internet are discussed.

PMID- 9513638
TI  - Lung cancer risk and welding: results from a case-control study in Germany.
AB  - In a case-control study, 839 male hospital-based cases of primary lung cancer and
      the same number of population-based controls--matched by sex, age, and region of
      residence--were personally interviewed for their job and smoking histories. The
      study allows to quantify occupational asbestos exposure that was thought to be a
      welding-associated risk: 6% of cases and 2% of controls were classified into the
      occupational category "welders or burners# (odds ratio [OR] = 2.65). This OR was
      reduced to 1.93 (95% confidence limit [CL]: 1.03-3.61) after adjustment for
      smoking and asbestos. In contrast, a history of welding in general for at least a
      half-year is 28% among cases and 23% among controls, yielding an OR of 1.25 (95%
      CL: 0.94-1.65) after adjustment for both confounders. The OR of welding for more
      than 6,000 hr is 1.45 (95% CL = 1.04-2.02), reduced to 1.10 after adjustment for
      smoking and asbestos. Oxyacetylene welding for more than 6,000 hr lifelong is
      associated with an OR of 1.86 (95% CL = 1.01-3.43) reduced to 1.46 (n.s.) after
      adjustment for smoking and asbestos. The risk of oxyacetylene welding seems to be
      highest for oat cell carcinoma with an adjusted OR for ever-exposure of 1.46 (95%
      CL = 0.69-3.10). Therefore, the present study supports the hypothesis that some,
      but not all, of the excess risk of welders observed in the literature may be due
      to a history of cigarette smoking and occupational asbestos exposure. The
      elevated risk for the subgroup of employees in the aircraft industry reported for
      the midterm evaluation of the study still prevails, though no longer
      statistically significant. However, employees in this industry who ever welded
      show an OR of 2.29 (95% CL = 1.19-4.42) after adjustment for smoking and
      asbestos.

PMID- 9513639
TI  - South African asbestos: production, exports, and destinations, 1959-1993.
AB  - Production and export figures of South African asbestos were analyzed over 1959
      1993. They show stable sales of chrysotile. Those of crocidolite and amosite
      reached their peaks in the mid-1970s, after which trade fell drastically,
      crocidolite to 5% of its earlier peak and amosite to nil. Factors responsible for
      these virtual collapses were health issues, stricter legislation in First World
      countries, and litigation. In 1992, 21 countries continued to import crocidolite,
      although in reduced quantities. In the early 1960s, Europe and North America were
      the major recipients of South African asbestos. By 1989-91, these regions were
      surpassed by the Far East, which took over 90% of chrysotile and 70% of amosite.
      For crocidolite at that time, the Middle East took nearly 40%, Europe 28%, and
      Africa 21%. This implies that the newly importing countries can confidently
      expect an increase in asbestos-related disease and death well into the twenty
      first century, even if the trade ceased now.

PMID- 9513640
TI  - Proportionate mortality among union members employed at three Texas refineries.
AB  - The cause-specific mortality (1940-1993) of 2,985 male workers employed in three
      oil refineries was examined using a proportionate mortality study design.
      Separate analyses were undertaken by race, refinery, employment status (active
      and retired), and time since entry into the Oil, Chemical, and Atomic Workers
      (OCAW) union. Proportionate cancer mortality ratio (PCMR) analyses also were
      conducted. Proportionate mortality ratios (PMR) were significantly increased (P <
      0.05) for cancers of the lip (PMR = 384), stomach (PMR = 142), unspecified sites
      of the liver (PMR = 238), pancreas (PMR = 151), connective tissues (PMR = 243),
      prostate (PMR = 135), eye (PMR = 407), brain (PMR = 181), benign and unspecified
      neoplasms (PMR = 289), and leukemia (PMR = 175) for the entire cohort.
      Significantly decreased mortality was observed for respiratory tuberculosis (PMR
      = 29), esophageal cancer (PMR = 45), rectal cancer (PMR = 49), and cancers of the
      bladder and other urinary organs (PMR = 40). Skin cancer was observed to be
      significantly increased (PMR = 242) for workers with less than 20 years since
      union initiation. Significantly increased PCMRs were seen for cancers of
      unspecified sites of the liver (PCMR = 205), brain (PCMR = 147), benign and
      unspecified neoplasms (PCMR = 243), and leukemia (PCMR = 146). Among nonwhites,
      an increased risk of bone cancer was observed in the PCMR analysis (PCMR = 704),
      although based on only two deaths. Analyses of mortality patterns for white males
      by refinery revealed similar patterns in each refinery as was seen in the overall
      cohort of refinery workers. Mortality patterns for whites and nonwhites also were
      similar. Additional analyses of deaths between 1960 and 1993 demonstrated
      increased mortality due to asbestosis (PMR = 683) and multiple myeloma (PMR =
      124), although the multiple myeloma excess was not statistically significant. Ten
      deaths due to mesotheliomas were observed among these refinery workers.

PMID- 9513641
TI  - Agricultural injuries among older Kentucky farmers: The Farm Family Health and
      Hazard Surveillance Study.
AB  - This population-based study reports the cumulative incidence of agricultural
      injuries during a 1-year period in a sample of 998 farmers aged 55 years and
      older living in Kentucky. A total of 98 farm-related injuries were reported among
      88 older farmers for a crude injury rate of 9.03 injured farmers per 100 farmers
      (95% confidence interval (CI) = 7.03-11.03) over a 1-year period. The leading
      external causes of farm injury were falls (24.9%), machinery (22.5%), wood
      cutting (14.6%), and animal-related events (14.3%). Farmers working on farms with
      beef cattle (alone) (odds ratio = 1.90; 95% CI = 1.02-3.55) or farms with beef
      cattle and tobacco (odds ratio = 2.15; 95% CI = 1.00-4.59) had a statistically
      significant increased risk for a farm-related injury. Farmers reporting a prior
      injury that limited their ability to farm were at increased risk for a farm
      related injury. Approaches to using farm injury surveillance data for injury
      control programs in the state are discussed.

PMID- 9513642
TI  - Industry-wide study of mortality of pulp and paper mill workers.
AB  - A study of pulp and paper mill workers indicated low risks of death from all
      causes (standardized mortality ratio (SMR) = 0.74) and all cancers (SMR = 0.81)
      compared with U.S. rates. The leukemia death rate in workers was not higher than
      the U.S. rate but was higher than the rate in county populations surrounding
      mills. Workers whose last jobs were in the finishing areas of the mills had an
      elevated SMR for liver cancer. An internal comparison of occupational
      characteristics indicated that workers employed in mills using other chemical
      pulping operations had significantly elevated mortality from all causes, all
      cancers, heart disease, lymphomas, and brain cancers. Lung cancer mortality was
      elevated in mills using kraft pulping. The internal comparisons confirmed the
      association between work in finishing and the risk of liver cancer. This study
      was designed to investigate whether pulp and paper mill workers have any risks
      that would indicate the need for studies detailing exposures.

PMID- 9513643
TI  - Mortality of a police cohort: 1950-1990.
AB  - This study presents findings from an updated retrospective cohort mortality study
      of male police officers from January 1, 1950 to December 31, 1990 (n = 2,593;
      58,474 person-years; 98% follow-up). Significantly higher than expected mortality
      rates were found for all cause mortality (Standardized mortality ratio [SMR] =
      110; 95% confidence interval [95% CI] = 1.04-1.17), all malignant neoplasms (SMR
      = 125; 95% CI = 1.10-1.41), cancer of the esophagus (SMR = 213; 95% CI = 1.01
      3.91), cancer of the colon (SMR = 187; 95% CI = 1.29-2.59), cancer of the kidney
      (SMR = 2.08, 95% CI = 100-3.82), Hodgkin's disease (SMR = 313; 95% CI = 1.01
      7.29), cirrhosis of the liver (SMR = 150; 95% CI = 1.00-2.16), and suicide (SMR =
      153; 95% CI = 1.00-2.24). All accidents were significantly lower (SMR = 53; 95%
      CI = 0.34-0.79). Mortality by years of police service showed higher than expected
      rates for (1) all malignant neoplasms in the 1- to 9-years-of-service group; (2)
      all causes, bladder cancer, leukemia, and arteriosclerotic heart disease in the
      10 to 19-year group; and (3) colon cancer and cirrhosis of the liver in the over
      30 years of service group. Hypotheses for findings are discussed.

PMID- 9513644
TI  - Median mononeuropathy among active workers: are there differences between
      symptomatic and asymptomatic workers?
AB  - The objective was to determine whether symptomatic workers with an abnormal
      sensory nerve conduction study consistent with carpal tunnel syndrome differed,
      in terms of electrophysiologic measures, psychosocial, demographic,
      anthropometric, or ergonomic variables, from workers with an asymptomatic median
      mononeuropathy. This was a cross-sectional study of active workers at six
      different work sites. Cases were defined as workers with electrodiagnostic
      findings of a median mononeuropathy in either hand, based on a 0.5-msec
      prolongation of the median sensory evoked peak latency compared to the ulnar
      latency. This group was stratified on the basis of symptoms of numbness,
      tingling, burning or pain in the hand. The two groups were compared in terms of
      demographic, anthropomorphic, psychosocial, electrophysiologic, and ergonomic
      risk factors. Active workers from six different sites were tested; five sites
      involved manufacturing workers, and one site represented clerical workers. One
      hundred eighty-four active workers with a median mononeuropathy were documented
      on nerve conduction studies. These workers represented a subset of more than 700
      workers screened at six different locations. The main outcome measure was the
      patient's report of symptoms of pain, numbness, tingling or burning in the hand
      or fingers that lasted more than 1 week or occurred three or more times at the
      initial screening. Workers with a median mononeuropathy who complained of hand
      symptoms were more likely to be female, to have jobs with higher hand repetition
      levels, to have higher ratings of job security, not to have a history of
      diabetes, to use more force in their job with more abnormal postures of their
      wrist and fingers, and to have a trend toward a more prolonged median sensory
      distal latency. Most logistic regression models explained less than 15% of the
      variance (pseudo R2). Women with jobs that have higher ergonomic risks and no
      history of diabetes were more likely to have reported symptoms associated with
      carpal tunnel syndrome compared to other workers with a documented median
      mononeuropathy. Psychosocial variables were not particularly discriminatory. None
      of the models allows enough precision to predict on an individual basis.

PMID- 9513645
TI  - A case of sarcoidosis that developed three years after the onset of hard metal
      asthma.
AB  - A 23-year-old man who worked at a hard metal factory from 1988 had developed
      bronchial asthma in 1990. He was diagnosed as having bronchial asthma by
      inhalation challenge with cobalt. He never developed a severe attack after that
      by avoiding inhalation of cobalt. In 1993, he developed iridocyclitis, and his
      chest radiograph showed bilateral hilar lymph node swelling. He was diagnosed as
      having sarcoidosis with pathological certainty and an increased serum angiotensin
      converting enzyme (ACE) level. On second admission, an inhalational challenge
      with cobalt resulted in no significant decrease of FEV1. Cobalt is well known to
      cause occupational asthma and other interstitial lung diseases. Although we could
      not get clear evidence suggesting an association between the sarcoidosis and his
      history of cobalt exposure, there is a possibility that changes in the immune
      reaction to cobalt might explain the improvement of asthma followed by
      sarcoidosis in this case.

PMID- 9513646
TI  - Acute lung function changes and low endotoxin exposures in the potato processing
      industry.
AB  - Work-related respiratory symptoms, acute lung function changes and personal
      endotoxin exposure were studied in 61 workers from a potato processing plant.
      According to their job title mean endotoxin exposure level, workers were divided
      into low (AM = 21 EU/m3) and high (AM = 56 EU/m3) exposure categories. Shortness
      of breath and chest tightness during work were reported by 18% and 16% of the
      workers, respectively, mainly in the low endotoxin exposure category. A total of
      148 across-shift lung function changes were measured during three consecutive
      afternoon shifts. The mean FEV1 and MMEF showed a decrease over the work shift,
      being largest on the first working day after a 3-day absence from work. Workers
      exposed to high endotoxin levels showed a larger across-shift decrease in lung
      function than workers exposed to low endotoxin exposures, the effect being most
      pronounced on the first day after a 3-day absence from work. At the start of the
      second work shift, FVC, FEV1 and MMEF were lower than at the start of the first
      work shift. This difference was larger for high exposed workers. High exposed
      workers with work-related respiratory symptoms showed an 8-10% across-shift
      change in FVC, FEV1 and MMEF We conclude that significant across-shift decreases
      in lung function of potato processing workers is related to endotoxin exposure
      levels above 53 EU/m3 over 8 hr.

PMID- 9513647
TI  - Biomarkers of nasal inflammation in wood-surface coating industry workers.
AB  - Upper airway symptoms in workers employed in the manufacture of wood products
      using ultraviolet radiation curing or acid curing of surface coating have been
      reported. In this study, workers were divided into groups according to exposure:
      (1) UV-surface coating line, (2) acid curing surface coating line, (3) finishing
      processes of UV-cured acrylate coated products, (4) finishing processes of of
      both UV- and acid cured coated wood products, and (5) control group. The workers
      were examined with nasal lavage in order to investigate inflammatory signs (ECP,
      tryptase, albumin and microscopy with cell differential counting). UV-line
      workers and finishers had significantly increased levels of ECP in nasal lavage.
      There was a positive correlation between exposure time and ECP and albumin
      levels. Workers with general nasal complaints and atopics had increased levels of
      ECP. In this study there were findings indicating an inflammatory process in the
      nasal mucosa in workers exposed to UV radiation curing multifunctional acrylate
      coatings. The findings indicate an unspecific inflammation and, therefore, a
      correlation between occupational exposure to acrylate coatings and nasal
      inflammation seems probable.

PMID- 9513648
TI  - Immunologic findings among lead-exposed workers.
AB  - A comprehensive panel of immune parameters was evaluated among 145 lead-exposed
      workers with a median blood lead level (BLL) of 39 micrograms/dL (range: 15-55
      micrograms/dL) and 84 unexposed workers. After adjusting for covariates, we found
      no major differences in the percentage of CD3+ cells, CD4+ T cells, CD8+ T cells,
      B cells, or NK cells between lead-exposed and unexposed workers, although the
      association between lead exposure and the number of CD4+ T cells was modified by
      age. We also found no differences between exposed and unexposed workers in serum
      immunoglobulin levels, salivary IgA, C3 complement levels, or lymphoproliferative
      responses. However, among exposed workers, the percentage and number of B cells
      were positively associated with current BLL, serum IgG was negatively associated
      with cumulative lead exposure, and the percentage and number of CD4+/CD45RA+
      cells were positively associated with cumulative lead exposure. We found no
      evidence of a marked immunotoxic effect of lead at the exposure levels studied,
      although some subtle differences in immunologic parameters were noted.

PMID- 9513650
TI  - Asbestos exposure: a potential cause of retroperitoneal fibrosis.
AB  - The etiology of retroperitoneal fibrosis is unknown in 70% of the cases. The aim
      of our study was to examine the possible association between occupational
      asbestos exposure and retroperitoneal fibrosis; only two cases have been reported
      in the literature. We gathered all the cases of retroperitoneal fibrosis
      diagnosed in the Tampere University Hospital between 1987 and 1995. We examined
      their hospital records to evaluate the possible etiology of the disease. We also
      sent a structured questionnaire to all living patients (10/13) to obtain
      information on their asbestos exposure. The chest radiographs of the patients
      were re-read to evaluate possible changes resulting from asbestos exposure. We
      found 13 cases of idiopathic retroperitoneal fibrosis. Seven patients (all male)
      had been exposed to asbestos in the past. The chest radiographs of the four most
      exposed patients showed characteristic asbestos-related abnormalities, including
      bilateral pleural plaques, round atelectasis and small irregular lung opacities.
      In our study, we found that asbestos exposure and asbestos-induced changes in the
      lung and pleura were common among male retroperitoneal fibrosis patients. We
      suggest that occupational exposure to asbestos may be an important etiological
      factor for retroperitoneal fibrosis.

PMID- 9513649
TI  - From cross-tabulations to multipurpose exposure information systems: a new job
      exposure matrix.
AB  - Previous job-exposure matrices (JEM) have usually cross-tabulated classified
      exposure information by chemical agent and occupational class. A new Finnish job
      exposure matrix (FINJEM) was constructed for exposure assessment in large
      register-based studies. Unlike most other JEMs, FINJEM was designed to contain
      definitions, inferences, exposure data, and references. This documentation
      enables FINJEM to be applied also as a general exposure information system for
      hazard control, risk quantification and hazard surveillance. The system includes,
      e.g., workforce data, and it provides information on the numbers of exposed
      workers in Finland by agent, occupation, and level of exposure. The exposures of
      FINJEM cover major physical, chemical, microbiological, ergonomic, and
      psychosocial factors. The assessment period is 1945-1997, divided into several
      subperiods. Exposure is described by the prevalence of exposure and the level of
      exposure among the exposed, both estimated mainly on continuous scales. The user
      may also define the final criteria of exposure, and thereby influence the
      magnitude of misclassification.

PMID- 9513651
TI  - A report card for occupational injuries and illnesses.

PMID- 9513652
TI  - Cytokines and adhesion molecules in allergic rhinitis.
AB  - This review summarizes our current knowledge of nasal allergic inflammation based
      on studies of cytokines, chemokines, and adhesion molecules in allergic rhinitis.
      The article also includes some aspects of viral rhinitis. Due to artificial or
      natural allergen exposure, an increase in the number of eosinophils and
      basophils, mast cells, IgE-positive cells, macrophages, monocyte-like cells,
      Langerhans cells, and activated T-cells can be observed within the mucosa and on
      the mucosal surface. Mediators are known to be released in response to allergens,
      but do not seem to be adequate to initiate the cell recruitment. After antigen
      challenge, the release of proinflammatory and regulatory cytokines could be
      demonstrated, and TH2-type cytokine mRNA upregulation in allergic mucosa has been
      shown. Proinflammatory cytokines initiate an adhesion cascade and activate T
      cells that create an "atopic" cytokine environment within the tissue, which also
      may be linked to the long-term selective recruitment of eosinophils. However, the
      acute selective migration of eosinophils after allergen challenge is not fully
      understood, nor is the role of chemokines in allergic and viral rhinitis.
      Allergic rhinitis clearly represents an inflammatory reaction.

PMID- 9513653
TI  - Neuropeptides.
AB  - Sensory, parasympathetic, and sympathetic nerves innervate many structures in
      airways. The anatomy, histology, and function of these nerves and their varied
      neurotransmitters will be reviewed. Changes that may contribute to the
      pathophysiology of allergic, viral, and nonallergic rhinitis will be described.

PMID- 9513654
TI  - Viral-induced rhinitis.
AB  - Upper respiratory viruses cause self-limited illness characterized by acute
      rhinitis. In rhinovirus colds the symptoms are thought to be caused by the host
      response rather than viral damage of the nasal epithelium. Rhinovirus triggers an
      inflammatory cascade, evidenced by the presence of inflammatory mediators (e.g.,
      IL-8) and proinflammatory cytokines (e.g., kinins) in nasal secretions, which
      results in symptomatic illness. In contrast to rhinovirus and coronavirus, which
      do not cause discernible epithelial damage, influenza virus and adenovirus do
      damage the nasal epithelium. Appropriate antiviral therapy will depend on the
      causative virus. Treatment of rhinovirus colds may require an antiviral agent
      (e.g., interferon alpha) in combination with antiinflammatory medication.

PMID- 9513655
TI  - Local corticosteroid treatment: the effect on cells and cytokines in nasal
      allergic inflammation.
AB  - Regular and prophylactic use of topical corticosteroids is a well tolerated and
      effective treatment for allergic rhinitis. The symptomatology of allergic
      rhinitis is considered to be the result of the accumulation and activation of
      infiltrating inflammatory cells, releasing mediators, and cytokines.
      Corticosteroids can suppress many stages of the allergic inflammatory process.
      This may explain their potent effect on allergic symptomatology. The reduction in
      cell numbers and probably also cytokines by local corticosteroid therapy differs
      from cell to cell. Some cells, such as antigen presenting (Langerhans) cells and
      eosinophils, are highly sensitive to corticosteroid treatment. Others, like T
      cells, are only significantly reduced in exaggerated situations, for instance
      after provocation with a high allergen dose or after treatment with a high dose
      of corticosteroids. Some cells, like macrophages, are not influenced at all.

PMID- 9513656
TI  - Induction in vivo of cartilage grafts for craniofacial reconstruction.
AB  - In the craniofacial region, defects of cartilage structures are preferably
      reconstructed with autologous cartilage. Donor-site morbidity related to the
      creation of a new defect elsewhere, and a lack of growth potential of the graft-
      mandatory in children--have stimulated investigators to find other ways to
      generate new "extra" cartilage. Several biomaterials have been tested as a matrix
      for the ingrowth of (peri)chondroblasts in experimental animals. In young
      (growing) rabbits we have developed a process of heterotopic cartilage induction
      with the use of a demineralized (bovine) bone matrix which is enfolded in a
      pedicled flap of ear perichondrium for at least three weeks. During this period
      the demineralized matrix is colonized by macrophages and polymorphonuclear cells
      which start a process of complete biodegradation of the material. Simultaneously,
      the collagen matrix is invaded by mesenchymal cells, originating from the
      perichondrium and differentiating into chondroblasts and later, into chondrocytes
      forming the intercellular substance. The developing, very young cartilage could
      be demonstrated as collagen type II, thus, hyaline cartilage. When applied with
      its adherent perichondrium as a graft, it merges easily with the more matured
      host cartilage and even appears to be capable of further growth. Therefore, it
      seems suitable for the reconstruction of a cartilaginous defect in growing
      cartilaginous structures like the nasal septum or the larynx.

PMID- 9513657
TI  - Perennial allergic rhinitis and nasal hyperreactivity.

PMID- 9513658
TI  - Nasal mucosal endorgan hyperresponsiveness.
AB  - Nonspecific hyperresponsiveness of the upper and lower airways is a well-known
      characteristic of different inflammatory airway diseases but the underlying
      mechanisms have not yet been satisfactorily explained. In attempts to elucidate
      the relation of hyperresponsiveness to disease pathophysiology we have
      particularly examined the possibility that different airway endorgans may alter
      their function in allergic airway disease. The nose, in contrast to the bronchi,
      is an accessible part of the airways where in vivo studies of airway mucosal
      processes can be carried out in humans under controlled conditions. Different
      endorgans can be defined in the airway mucosa: subepithelial microvessels,
      epithelium, glands, and sensory nerves. Techniques may be applied further in the
      nose to determine selectively the responses/function of these endorgans. Topical
      challenge with methacholine will induce a glandular secretory response, and
      topical capsaicin activates sensory c-fibers and induces nasal smart. Topical
      histamine induces extravasation of plasma from the subepithelial microvessels.
      The plasma exudate first floods the lamina propria and then moves up between
      epithelial cells into the airway lumen. This occurs without any changes in the
      ultrastructure or barrier function of the epithelium. We have therefore forwarded
      the view of mucosal exudation of bulk plasma as a physiological airway tissue
      response with primarily a defense function. Since the exudation is specific to
      inflammation, we have also suggested mucosal exudation as a major inflammatory
      response among airway endorgan functions. Using a "nasal pool" device for
      concomitant provocation with histamine and lavage of the nasal mucosa we have
      assessed exudative responses by analyzing the levels of plasma proteins (e.g.,
      albumin alpha 2-macroglobulin) in the returned lavage fluids. A secretory
      hyperresponsiveness occurs in both experimental and seasonal allergic rhinitis.
      This type of nasal hyperreactivity may develop already 30 minutes after allergen
      challenge. It is attenuated by topical steroids and oral antihistamines. We have
      demonstrated that exudative hyperresponsiveness develops in both seasonal
      allergic rhinitis and common cold, indicating significant changes of this
      important microvascular response in these diseases. An attractive hypothesis to
      explain airway hyperresponsiveness has been increased mucosal absorption
      permeability due to epithelial damage, possibly secondary to the release of
      eosinophil products. However, neither nonspecific nor specific endorgan
      hyperresponsiveness in allergic airways may be explained by epithelial fragility
      or damage since nasal absorption permeability (measured with 51CR-EDTA and dDAVP)
      was decreased or unchanged in our studies of allergic and virus-induced rhinitis,
      respectively. Thus, the absorption barrier of the airway mucosa may become
      functionally tighter in chronic eosinophilic inflammation.

PMID- 9513659
TI  - Nasal polyps and their relation to polyps/hypertrophic polypoid mucosa in the
      paranasal sinuses: a macro-, endo-, and microscopic study of autopsy materials.
AB  - The present study comprised macro- and endoscopic screening of the nasosinusal
      complex in 56 autopsies, 24 with nasal polyps and 32 without. Seven had nasal
      polyposis (bilaterally more than two). Hypertrophic polypoid mucosa in the
      paranasal sinuses was not found in the cases with nasal polyposis and in only 2
      (4%) of the total number (24) of cases with polyps. Microscopic examination of
      nine small polyps, the mucosa from which they originated, and control specimens
      showed accumulation of eosinophils in the mucosa from which the polyps
      originated, indicating localized inflammation.

PMID- 9513660
TI  - Correlations among mucociliary transport, ciliary function, and ciliary
      structure.
AB  - Mucociliary transport is one of the most important defense mechanisms of the
      airway. Mucociliary transport time or rate, as measured using the saccharin test
      or the radioisotope technique, respectively, is clinically the most relevant
      parameter, although subject to large intra- and interindividual variability.
      There is no correlation between mucociliary transport in vivo and ciliary beat
      frequency ex vivo. Preliminary evidence demonstrates that mucociliary transport
      correlates with ciliary structure and orientation as investigated with
      transmission and scanning electron microscopy. A correlation is presented between
      ciliary beat frequency and secondary ciliary abnormalities. This correlation can
      best be described according to the logistic sigmoid model (r = 0.69). Based on
      these functional data, an ultrastructural distinction is proposed among normal
      (less than 5%), light (5 to 15%), moderate (15 to 25%), and severe (more than
      25%) secondary ciliary dyskinesia.

PMID- 9513661
TI  - Tissue engineering of autologous cartilage transplants for rhinology.
AB  - In reconstructive surgery there is increasing demand for cartilage transplants to
      fill defects, especially nose and/or outer ear defects. Tissue engineering is one
      of the most modern pathways to generate autologous cartilage transplants.
      Isolated chondrocytes obtained from a tiny patient's biopsy were seeded on
      bioresorbable preshaped cell carriers to provide a 3-dimensional cell arrangement
      as in vivo. The combined use of these cell carriers in form of a non-woven mesh
      and a constant medium perfusion was performed to generate a cartilage-like cell
      polymer-construct, which was finally subcutanously implanted in nude mice for
      full maturation. After explantation of 6 months, expression of cartilage specific
      extracellular matrix molecules was obvious by using histochemical and
      immunohistochemical methods. These data show that tissue engineering with
      isolated multiplied human chondrocytes from a tiny biopsy seeded on bioresorbable
      polymer is a promising system to generate autologous cartilage transplants for
      replacements in reconstructive surgery.

PMID- 9513662
TI  - Noninfectious, nonallergic rhinitis (NINAR): considerations on possible
      mechanisms.
AB  - Most patients who suffer from chronic noninfectious, nonallergic rhinitis (NINAR)
      cannot be assigned to a syndrome of known etiology. The symptomatology may well
      resemble that of allergic rhinitis; however, NINAR has lower prevalence of
      sneezing, conjunctival symptoms, and pruritus and higher prevalence of symptoms
      compatible with sinus disease. The triggers for the symptoms of NINAR are mainly
      irritants and changes in atmospheric conditions. Among individuals who develop
      chronic rhinitis symptoms, the percentage of nonallergic etiology increases
      steadily with age and is more than 60% beyond the fifth decade of life. Our
      strategy regarding the pathophysiology of NINAR should be to identify functional
      abnormalities of nasal mucosa that can potentially result in the alleged nasal
      symptoms. In this respect, comparison of patients with NINAR to patients with
      allergic rhinitis and to healthy individuals could shed light into the cause(s)
      of NINAR. Three potential functional abnormalities are discussed in this article:
      those associated with the aging process of the nasal mucosa, those resulting in
      various forms of nasal hyperreactivity, and those reflecting imbalanced neuronal
      control of end organs of the nose. The most interesting development in the
      therapy of NINAR is the use of capsaicin. Although placebo-controlled studies are
      scarce and participants have not been adequately characterized, it is possible
      that abnormal nociceptor nerve endings play a role in the generation of the
      symptoms of NINAR. Alternatively, NINAR may represent a condition of increased
      perceptual acuity to irritants and to environmental changes. This problem may
      also benefit from defunctionalization of nociceptors.

PMID- 9513663
TI  - Liquid ventilation.

PMID- 9513664
TI  - Transoesophageal echocardiography in the intensive care unit.
AB  - The role of transoesophageal echocardiography (TOE) in a general intensive care
      unit was examined by reviewing all studies performed in a major metropolitan
      hospital over a two-year period. TOE was performed on 53 patients where
      transthoracic studies were inadequate, the indications being cardiac source of
      embolus (13/53), thoracic aorta abnormalities (5/53), left ventricular systolic
      function (22/53), endocarditis (6/53), right heart pathology (2/53), pulmonary
      embolus (2/53), or a potentially surgical correctable lesion (3/53). Findings
      were categorized into three groups: confirming suspected pathology (18/53), major
      incidental findings (6/53), or normal (29/53). Patient management was altered,
      not only by the finding of positive pathology, but also after identifying normal
      left ventricular systolic function (14/53). Echocardiography has become an
      invaluable tool in the ICU setting.

PMID- 9513665
TI  - Pulmonary hypertension and selective pulmonary vasodilators in acute lung injury.
AB  - The pulmonary circulation and the mechanisms which generate pulmonary
      hypertension are reviewed. The role of these mechanisms in the common pulmonary
      hypertensive states are analysed, particularly those in acute lung injury.
      Management options are discussed, with particular emphasis on the use of
      selective pulmonary vasodilators.

PMID- 9513666
TI  - The effects of antivenom and verapamil on the haemodynamic actions of Chironex
      fleckeri (box jellyfish) venom.
AB  - The efficacy of antivenom and verapamil against Chironex fleckeri (box jellyfish)
      venom was investigated in monitored mechanically ventilated piglets. Chironex
      fleckeri tentacle extract alone, a mixture of tentacle extract with antivenom,
      and verapamil before tentacle extract were administered intravenously to groups
      of animals. Tentacle extract caused severe systemic hypotension, cardiac
      dysrrhythmias, pulmonary hypertension, haemolysis and hyperkalaemia. These
      effects were prevented by pre-incubation of tentacle extract with antivenom.
      Verapamil did not prevent any effect of venom, exacerbated cardiovascular
      collapse and increased mortality. We conclude that antivenom neutralizes the
      cardiovascular, haemolytic and hyperkalaemic effects of box jellyfish venom.
      Verapamil does not prevent any of these effects and is contra-indicated for
      treatment of envenomation.

PMID- 9513667
TI  - Validation of air as an equilibration medium in gastric tonometry: an in vitro
      evaluation of two techniques for measuring air PCO2.
AB  - This laboratory-based bench study was undertaken to evaluate the accuracy and
      equilibration characteristics of air and saline respectively as CO2 equilibrating
      media in the silicone balloon of a gastric tonometer and to compare two methods
      of measuring air PCO2. Two gastric tonometers were suspended in a bath containing
      0.9% saline maintained at 37 degrees C. Certified calibration gases at three
      different CO2 concentrations were bubbled into the bath. When the bath PCO2
      measurement was stable the tonometers were primed with 5 ml of air and 2.5 ml
      normal saline respectively and allowed to equilibrate for 30 and 90 minutes.
      Following equilibration, samples were aspirated and analysed in duplicate in a
      blood gas analyser. Bias and precision were calculated from the measured and
      expected PCO2 values. A consistent negative bias (21-23%) was seen with air at
      all three CO2 concentrations at 30 and 90 minutes with a coefficient of variation
      between 2.7 and 3.3%. Imprecise data were obtained with saline at different
      levels of CO2. A similar experimental set-up was used to compare air PCO2
      measurement by a blood gas analyser and an infra-red analyser (Tonocap). Similar
      bias was obtained with the blood gas analyser with respect to air PCO2
      measurement as in experiment 1. The infra-red analyser measurement was highly
      precise with negligible bias. Air appears to be a better CO2 equilibration medium
      during bench testing of tonometry producing a systematic negative offset and
      requiring a uniform correction factor of 1.25. This correction factor is
      independent of equilibration time and equilibrating CO2 concentration. The use of
      the infra-red analyser eliminates any bias in the measurement of air PCO2 and
      obviates the need for a correction factor.

PMID- 9513668
TI  - Microbial contamination of three-way taps on arterial lines.
AB  - Arterial lines with three-way taps are used to measure blood pressure and
      aspirate blood, and are a potential source of catheter-related sepsis. Swabs were
      taken daily from 118 three-way taps on 98 arterial lines in a general intensive
      care unit. Infusion lines were changed weekly but arterial cannulae were not
      changed routinely. An overall contamination rate of 24.6% was found with the
      predominant organism being coagulase negative staphylococcus. The three-way taps
      became increasingly contaminated with time but this was shown to be unrelated to
      the manipulation rates. Blood culture organisms in those showing contamination of
      the three-way taps showed no relationship to the bacteria causing the
      contamination.

PMID- 9513669
TI  - Intravenous tenoxicam for analgesia following laparoscopic cholecystectomy.
AB  - In a double-blind, placebo-controlled clinical trial (power of 80% to detect a
      30% reduction in morphine consumption, P < 0.05) we have determined that
      intraoperative intravenous administration of tenoxicam 40 mg during laparoscopic
      cholecystectomy, when compared with placebo, was associated with a significant
      reduction in consumption of morphine at 6 hours and 12 hours (P < 0.05) but not
      at 24 hours, when assessed by patient-controlled analgesia. Furthermore there was
      a significantly greater requirement for "rescue" analgesia with intramuscular
      morphine in the placebo group during the period of the study. There was no
      difference between the groups in pain scores, either at rest or on movement, nor
      in the incidence of nausea and vomiting. No patient in either group suffered a
      respiratory rate less than 8/min or oversedation at any time, and there were no
      other adverse effects.

PMID- 9513670
TI  - Depth of central venous catheter insertion in adults: an audit and assessment of
      a technique to improve tip position.
AB  - A technique of subclavian vein catheterization is described, tailored to the
      individual patient, to reduce the risk of right atrial placement with central
      venous catheter (CVC) insertion. Using data gathered retrospectively for Quality
      Improvement purposes, CVC tip location was assessed. The standard technique used
      in our cardiac anaesthesia unit at that time was to insert all CVCs to a depth of
      15 cm from the skin. We then compared CVC tip location using a new "tailored"
      technique. The tailored method involved measuring the distance from the skin at
      which venepuncture occurred and using this distance to determine depth of CVC
      insertion. Using the tailored technique significantly decreases the frequency
      with which CVC tips enter the right atrium (P < 0.001). An advantage of the
      tailored technique is that the distance between the most proximal and the distal
      ports of multi-lumen CVCs is taken into consideration, reducing the risk of
      extravasation via the proximal port.

PMID- 9513671
TI  - An evaluation of a new analyser for inhaled nitric oxide administration.
AB  - We examined the ability of a new combined nitric oxide (NO)/nitrogen dioxide
      (NO2) electrochemical analyser (PrinterNOx, Micro Medical Limited, Chatham, Kent,
      England) to measure NO and NO2 concentrations. The PrinterNOx was compared to a
      chemiluminescence analyser (42H, Thermo Environmental Instruments Inc, Franklin
      MA, U.S.A.). NO and NO2 were generated in a standard ventilator circuit using a
      paediatric ventilator (900C, Siemens Elema, Sweden) connected to an artificial
      lung (260li, TTL Test Lung, Michigan Instruments, MI, U.S.A.). Forty-four paired
      NO measurements ranging from 2.56 ppm to 74.6 ppm and 50 paired NO2 measurements
      ranging from 0.0 ppm to 5.39 ppm were obtained. For the measurement of NO the
      PrinterNOx showed a tendency to overestimate the chemiluminescence analyser.
      Regression analysis showed a close relationship between the two analysers with r2
      = 0.9981 and a regression equation of y = 1.1658 x +0.0197. In the more
      clinically important range of 0-25 ppm, r2 increased to 0.9996 with a regression
      equation of y = 1.1984 x -0.4657. Conversely the PrinterNOx underestimated the
      chemiluminescence analyser for the measurement of NO2. The regression equation
      describing this relationship was y = 0.879 x -0.0447 (r2 = 0.9993). We conclude
      that the PrinterNOx is of sufficient accuracy to be of clinical use in the
      administration of NO.

PMID- 9513672
TI  - Anti-aspiration prophylaxis in New Zealand: a national survey.
AB  - A postal questionnaire was sent on two occasions to specialist anaesthetists
      within New Zealand. Questions were related to fasting status, anti-aspiration
      prophylaxis, incidence of aspiration, definition of high risk groups for
      aspiration pneumonitis, and identification of departmental guidelines. Two
      hundred-and-twenty-three replies were received (72% response rate). Most adults,
      children and infants were fasted for 6 hours for solids, whilst the majority
      fasted for 2 to 4 hours for liquids. Two-thirds indicated that they would delay
      emergency surgery (not life/limb threatening) to optimize gastric emptying.
      Histamine type 2 receptor antagonists, metoclopramide and cricoid pressure were
      used commonly, more so in the obstetric population compared to non-obstetric
      surgery. Preinduction nasogastric intubation and suction were used infrequently.
      Anti-aspiration prophylaxis was deemed important in morbidly obese patients,
      those in the third trimester of pregnancy and those with a hiatus hernia, whilst
      diabetes mellitus, sepsis and renal failure were not considered risk factors for
      aspiration pneumonitis. 71% of respondents had at least one episode of aspiration
      (range 0-10), with an overall mortality rate of 5%. Half of these cases of
      aspiration were deemed to be preventable by the respondent.

PMID- 9513673
TI  - Unpacking the burden: gender issues in anaesthesia.
AB  - A survey carried out by the Australian Society of Anaesthetists explored gender
      issues in the personal and professional lives of anaesthetists. Issues
      highlighted include training and career paths, combining anaesthetic training
      with domestic responsibilities, personal relationships, pregnancy and
      childrearing, private practice, part-time work, parental leave, the single
      anaesthetist, doctor spouses, sexual harassment, and negative attitudes in
      colleagues. Particular problems were identified in the training years, in part
      time work, in private practice, and in combining parental and domestic
      responsibilities with a career in anaesthesia. Strategies to address relevant
      issues are discussed, with reference to the increasing proportion of women in
      medicine and anaesthesia.

PMID- 9513674
TI  - Anaesthesia for aboriginal Australians.
AB  - This prospective study was designed to describe problems that arise when
      Aboriginal people undergo anaesthesia, in order to develop guidelines for
      anaesthetists who are not accustomed to treating Aboriginal people. Data were
      collected on 1122 consecutive different individuals undergoing anaesthesia at
      Royal Darwin Hospital, 24.5% of whom described themselves as Aboriginal.
      Aboriginal patients were in a poorer physiological state than were non-Aboriginal
      patients. The prevalence of diabetes mellitus, renal disease and rheumatic heart
      disease reported in Aboriginal patients was very high. Communication difficulties
      were more commonly reported in Aboriginal patients; the most common difficulty
      was apparent shyness or fear, rather than actual language difficulty. The results
      suggest that the treatment of Aboriginal people involves diagnosis and management
      of diverse preoperative medical problems, and that better management may be
      achieved by learning simple cultural strategies and by adding Aboriginal
      interpreters and health workers to the anaesthetic team.

PMID- 9513675
TI  - Trainees' attitudes to research as part of anaesthetic training.
AB  - The formal project has been a requirement for the F.A.N.Z.C.A. diploma for the
      past few years. A questionnaire was sent to all registrars on a formal program
      asking questions relating to the formal project, perceived advantages,
      disadvantages, value of formal research teaching methodology and future career
      intentions. All years of training were represented. Forty-nine of the fifty-six
      (86%) respondents replied to the survey. Of these 15% felt the formal project had
      no value, 54% found it possibly useful whilst 31% perceived is as very useful.
      Advantages of the formal project included appreciation of research skills and the
      ability to critically appraise research. Disadvantages included lack of dedicated
      time, space and funding and production of poor quality research. A majority (63%)
      favoured formal teaching of research methods for the F.A.N.Z.C.A. diploma, which
      ideally should be taught before the Primary (30%) or in the Provisional
      Fellowship year (36%). Few respondents indicated a willingness to undertake a
      major commitment to research in the future (4%) but 46% wanted some contact with
      research and teaching as part of their normal work practice. A more structured
      teaching in research methodology, assessment of published work and presentation
      skills may be more suited to the longterm goals of the majority of clinical
      anaesthetists.

PMID- 9513676
TI  - Spinal anaesthesia--the current trend towards narrow gauge atraumatic (pencil
      point) needles. Case reports and review.
AB  - Advances in manufacturing technology have led to the wider availability and
      affordability of narrow gauge atraumatic spinal needles. The use of these needles
      is the most effective method available for anaesthetists to reduce the incidence
      of post dural puncture headache. Their use in all circumstances however, may not
      be appropriate in light of the problems which may be associated. These problems
      are illustrated here by four case reports and a review of the literature.

PMID- 9513677
TI  - Severe hypotension associated with angiotensin-converting enzyme inhibition in
      anaesthesia.
AB  - Three cases of severe hypotension associated with the use of angiotensin
      converting enzyme inhibitors (ACEIs) and intravenous administration of the
      synthetic colloid Gelofusin (Braun Medical Ltd) are presented. A possible
      mechanism of interaction between ACEIs and Gelofusin is discussed. All three
      patients were treated successfully.

PMID- 9513678
TI  - Airway management for an uncooperative patient with recessive dystrophic
      epidermolysis bullosa.
AB  - We describe a case of an unco-operative patient with recessive dystrophic
      epidermolysis bullosa in whom difficult tracheal intubation was anticipated and
      fibreoptic bronchoscope guided tracheal intubation was successfully achieved
      after induction of general anaesthesia. Other problems in airway management
      associated with this disorder are discussed.

PMID- 9513679
TI  - Venous embolism of diathermy evolved gases complicating endometrial ablation
      using glycine irrigant.
AB  - A case is reported of venous gas embolism in a 44-year-old woman undergoing
      hysteroscopic endometrial ablation using glycine irrigation without gas
      insufflation. The postulated source of gases are the vapour and combustion
      products produced by the diathermy.

PMID- 9513681
TI  - Knotting of nasogastric tube.

PMID- 9513680
TI  - Continuous extrapleural intercostal nerve block for post thoracotomy analgesia in
      children.

PMID- 9513683
TI  - Infusion pumps and MRI.

PMID- 9513682
TI  - Unintentional bolus with Graseby 9300 pump.

PMID- 9513684
TI  - Dapsone methaemoglobinaemia.

PMID- 9513686
TI  - Fractal tumor stromal border in a nonequilibrium growth model.
AB  - OBJECTIVE: To examine the potential relationships of tumor growth parameters and
      fractal dimensionality of the resulting pattern. STUDY DESIGN: A nonequilibirum
      tumor growth model was developed taking into account tumor cell motility, tumor
      and stromal proliferation, cohesion, autocrine and paracrine growth stimulation,
      and tumor and stromal destruction. Ten thousand simulation runs were performed
      with varying settings of the control parameters. Fractal dimensionality of the
      tumor-stroma border was assessed in each pattern by a box counting method.
      RESULTS: Fractal dimensionality increased with overall tumor cell motility,
      heterotypic tumor-stroma adhesion and paracrine growth stimulation, and decreased
      with homotypic tumor-tumor adhesion, autocrine growth stimulation, and tumor and
      stroma destruction. CONCLUSION: Fractal dimensionality of the tumor-stroma border
      depends on various parameters controlling tumor growth. Some growth properties
      considered to be associated with an increased degree of malignancy influence
      fractal dimensionality in opposite directions. Therefore, determination of
      fractal dimensionality cannot be related directly to any particular biologic
      feature or to the overall biologic behavior of a tumor.

PMID- 9513685
TI  - Quantitative comparison of apoptosis to cell proliferation and p53 protein in
      breast carcinomas.
AB  - OBJECTIVE: To clarify the correlation between apoptosis and tumor cell
      proliferative activity in human breast cancer and to investigate their relevance
      to p53 protein. STUDY DESIGN: Seventy-one breast carcinomas with histologic
      grading were analyzed, using counting of mitotic activity index (MAI) and
      apoptotic index (AI) to examine apoptosis and cellular proliferation, which were
      then compared with the expression of p53 protein by using a semiquantitative
      immunohistochemical method. RESULTS: Both the mean MAI and AI were significantly
      higher in the grade 3 groups (18.30 +/- 2.18 SE, 13.58 +/- 1.94) and 2 (11.32 +/-
      1.30, 9.96 +/- 1.84) than in the grade 1 groups (8.24 +/- 1.10, 8.30 +/- 2.20) (P
      < .001). Also, MAI/AI was significantly highest in the grade 3 group (P < .001).
      A significant correlation was found between MAI and AI (r = .767, P < .01).
      Positive expression of p53 protein, indicated by distinct nuclear staining, was
      found in 35 of 71 carcinomas and was related to neither MAI nor AI (P > .05);
      there was no significant relation between p53-positive scoring and histologic
      grading (P > .05). CONCLUSION: Apoptosis in breast cancer seems to correlate with
      proliferative activity assessed by the mitotic index and supports the hypothesis
      that apoptosis may play a role in the selection of clonal subpopulations with
      high growth potential but is not regulated by the p53 system. Further research
      needs to be conducted to elucidate the relation between apoptosis and tumor
      progression and the significance of p53 in abnormalities in breast cancer.

PMID- 9513687
TI  - Rapid and reliable assessment of volume percentage of epithelium in borderline
      and invasive ovarian tumors.
AB  - OBJECTIVE: To analyze factors determining intraobserver and interobserver
      reproducibility of stereology in borderline and invasive ovarian tumors. STUDY
      DESIGN: Fast and simple assessment of VPE was possible by using a highly
      automated interactive video overlay system suitable for application in a routine
      pathology laboratory. The point distance of a Weibel grid and the number of
      fields of vision per area of interest required to obtain good reproducibility
      were investigated. In addition, intraobserver and interobserver reproducibility
      was assessed, and the results of the improved technique were compared to those of
      the classical method. RESULTS: The experiments showed that intraobserver and
      interobserver variations in volume percentage of epithelium (VPE) assessments in
      a given case were caused mainly by high field-to-field variation and not so much
      by differences in the precision of assessment in a single field of vision.
      Therefore, many fields but only few points per field need to be measured to
      obtain, in a short time, a precise estimate of VPE in the measurement area of a
      tumor. From these results, an optimized protocol for VPE assessment was
      constructed. Using this protocol, nine observers independently assessed VPE in
      seven cases. Counting only one point in each of 100 systematically randomly
      sampled fields of vision (corresponding to a point distance of +/- 560 microns)
      yielded high intraobserver reproducibility (coefficient of variation [CV], 4%; R,
      .99; range, 0.98-1.00) and interobserver reproducibility (CV, 6%; R, .98; range,
      0.97-1.00) in a short time. Assessment of one case took approximately three
      minutes, and the observers experienced the work as pleasant. CONCLUSION: VPE
      assessed with systematic random sampling, using a grid with one point per field
      of vision and counting 100 hits, yields an inexpensive, fast and highly
      reproducible measure of an important prognostic variable in ovarian tumors. This
      assessment can be performed easily in a routine pathology laboratory.

PMID- 9513688
TI  - Nuclear morphometry in solar keratosis.
AB  - OBJECTIVE: To carry out a feasibility study for the development of procedures for
      the objective characterization and grading of solar keratotic skin lesions. STUDY
      DESIGN: Imagery from sections of skin shave biopsies from 12 light-skinned
      individuals were digitized. A minimum of 25 nuclei from a solar keratotic lesion
      and 25 nuclei from a location in histologically normal appearing skin adjacent to
      the lesion were recorded for each case. Values of karyometric features were
      computed, and a discriminant function distinguishing normal nuclei from nuclei
      exhibiting solar irradiation damage was derived. RESULTS: Approximately 50% of
      nuclei in solar keratotic lesions were markedly affected by solar irradiation,
      but even in biopsies from histologically normal appearing skin, 3-30% of nuclei
      showed signs of such damage. Nuclei from solar keratotic lesions exhibiting such
      damage had numerous morphometric and karyometric features commonly found in
      malignant cells. The state of progression of a solar keratotic lesion can be
      graded by a plot of proportion of nuclei exhibiting solar damage versus the
      average discriminant function score of the most affected nuclei. This plot
      provides a monotonically rising progression curve and a numeric grading score.
      CONCLUSION: Karyometry of nuclei from skin biopsies allows objective assessment
      of the progression of solar keratotic lesions. Similarity of feature values in
      nuclei from solar keratotic lesions to those in malignant lesions was noted. The
      progression curve derived in this study could serve to measure the efficacy of
      chemopreventive or therapeutic intervention.

PMID- 9513689
TI  - Comparison of quantitative variables between patients with relatively normal and
      gastritis-altered mucosae.
AB  - OBJECTIVE: To develop a statistical (regression) analysis of quantitative
      patterns of human epithelial nuclear and cellular profiles from chronic atrophic
      and hypertrophic gastritis, excluding Menetrier's gastropathy. STUDY DESIGN: The
      study group consisted of 30 patients with chronic gastritis with or without
      intestinal metaplasia, including gastric dysplasia. The control group consisted
      of 25 patients with relatively normal mucosae. Both groups were compared with
      respect to changes in quantitative morphometric variables as well as nuclear DNA
      quantities. RESULTS: Specific interdependences between minor (BN) and major (LN)
      nuclear axis length and cellular caliper diameters (Bc) and (Lc) were stipulated;
      thus, the corresponding area features were determined by regression equations.
      The value of the L2 norm as differences between corresponding linear functions
      involved in the regression equations were also examined. Higher nuclear DNA
      content values were obtained from patients with chronic gastritis. CONCLUSION:
      Chronic gastritis appears to be an intermediate and crucial moment in the process
      of gastric mucosal malignant progression. The pentaploid (5C) region was found to
      be an intermediate and critical feature of chronic gastritis since values in the
      ploidy range higher than pentaploid have been found to potentially indicate a
      malignancy.

PMID- 9513690
TI  - Prognostic relevance of DNA image cytometry in oral cavity carcinomas.
AB  - OBJECTIVE: To evaluate the relation of DNA content of squamous cell carcinomas of
      the oral cavity to clinicopathologic features by image cytometry. STUDY DESIGN: A
      series of 52 patients with operable oral cavity carcinomas at stage T1-4 and NO-3
      were studied. The tumors were classified according to the TNM classification and
      graded histopathologically. RESULTS: A positive correlation between tumor size
      and ploidy status was observed. There was a significant correlation between
      ploidy status and histologically proven existence of cervical lymph node
      metastases (61% nondiploid versus 29% diploid, P < .03). A relationship between
      histopathologic grade and ploidy status could not be proven. The cumulative five
      year survival rate among patients with diploid DNA findings as opposed to those
      with nondiploid findings was significantly increased (P < .03). CONCLUSION: When
      assessing the prognosis of squamous cell carcinomas, DNA cytometry analysis can
      be used as an additional method. The significantly higher N stage, a higher
      frequency of metastases and a significantly lower survival rate with nondiploid
      tumors underline the importance of this examination method.

PMID- 9513691
TI  - Flow cytometric analysis of DNA content in gastric and colorectal cancer.
AB  - OBJECTIVE: Analysis of DNA ploidy and proliferative activity by flow cytometry
      (FCM) of gastric (GC) and colorectal cancer with morphology (histology and
      cytology) and prognostic correlation was performed. STUDY DESIGN: The study group
      consisted of 160 patients with GC (93) and colorectal cancer (CRC) (67). Tumor
      samples were taken by gastric and colon biopsy. All patients subsequently
      underwent surgery. DNA content was assessed using an ICP II cytometer (Phywe,
      Germany). Two samples were taken from the tumor, one for cytology and FCM and the
      other for histology. Macroscopically, unchanged mucosa served as a control group.
      Three types of DNA histogram were distinguished in accordance with the ploidy and
      proliferative activity of the tumor. RESULTS: The number of aneuploid and diploid
      tumors was the same in GC and CRC and reached 53% (49/93) and 66% (44/67),
      respectively (P > .05). Morphologic study discovered predominance of
      adenocarcinoma in both GC and CRC, with mainly poor differentiation (53/93) in GC
      and moderate and high differentiation in CRC (49/67). There was a large group of
      signet-ring cell GCs (18, 19.4%), while in CRC this was diagnosed in 4 (6.0%)
      cases only. Poorly differentiated adenocarcinomas were significantly more
      frequent among aneuploid tumors (41/49 in GC and 13/44 in CRC) than among diploid
      tumors (12/44 in GC and 0/23 in CRC). Five-year survival in GC (89) and CRC (64)
      strongly correlated with DNA histogram type. Survival was the highest in patients
      with DNA histogram type I (diploid tumor and poor proliferative activity). The
      poorest prognosis was associated with aneuploidy and high proliferative activity
      of cells (DNA histogram type III). CONCLUSION: The differences between DNA
      histogram types indicate that survival depends to a greater degree upon
      proliferative activity of tumor cells than upon tumor ploidy.

PMID- 9513692
TI  - Liver cell proliferation after partial hepatectomy in rats with liver metastases.
AB  - OBJECTIVE: To validate proliferating cell nuclear antigen (PCNA) expression and
      flow cytometry as proliferation markers in regenerating rat liver containing
      metastases. STUDY DESIGN: Rats containing colorectal liver metastases were killed
      at various days after 70% partial hepatectomy or a sham operation. [3H]thymidine
      and 5-bromo-2'deoxyuridine (BrdU) incorporation, PCNA expression and flow
      cytometry were used to evaluate liver cell proliferation. RESULTS: The assessment
      of proliferating liver cells by PCNA expression and BrdU incorporation was more
      reliable than autoradiography. PCNA expression correlated well with BrdU
      incorporation (r = .68, P = .003) and autoradiography (r = .57, P = .02) in
      regenerating liver. BrdU incorporation and PCNA expression were higher in
      hepatectomized rats as compared to sham-operation rats at days 1-4 after
      hepatectomy. Flow cytometry of propidium-stained nuclei from livers of
      hepatectomized rats showed a higher proportion of S-phase nuclei as compared to S
      phase nuclei in control rats. The correlation coefficients of the number of S
      phase nuclei, BrdU-positive nuclei and PCNA-positive nuclei were .39 (P < .02)
      and .56 (P < .0005), respectively. CONCLUSION: Flow cytometry and PCNA expression
      are simple and reliable methods of studying proliferation in metastases
      containing rat liver after partial hepatectomy.

PMID- 9513693
TI  - Value of computer-assisted quantitative nuclear grading in differentiation of
      normal urothelial cells from low and high grade transitional cell carcinoma.
AB  - OBJECTIVE: To evaluate the ability of computer-assisted quantitative nuclear
      grading (QNG) using a microspectrophotometer and morphometry software to
      differentiate Feulgen-stained nuclei captured from normal urothelium, low grade
      transitional cell carcinoma (LG-TCC) and high grade transitional cell carcinoma
      (HG-TCC) cytology specimens. STUDY DESIGN: Feulgen-stained nuclei from a series
      of normal volunteers (urologic disease-free history) and from biopsy-confirmed
      cases of LG-TCC and HG-TCC were evaluated using a CAS-200 image analysis system.
      Thirty-eight nuclear morphometric descriptors (NMDs) were measured for each
      nucleus using a software conversion system. Backwards stepwise logistic
      regression analysis was applied to assess which of the NMDs contributed to QNG
      statistical models that could differentiate between nuclei from normals vs. LG
      TCC, normals vs. HG-TCC, and LG-TCC vs. HG-TCC. Receiver operating characteristic
      curves and areas under the curve (AUC), as well as cell classification accuracy,
      were used to assess these differences. RESULTS: Statistically significant
      differences (P < .0001) were observed between all three categories. In the LG-TCC
      vs. normals, the QNG solution model required 16/38 features, with an AUC = 93%, a
      sensitivity = 85%, specificity = 86%, positive predictive value (PPV) = 87% and
      negative predictive value (NPV) = 84%. The QNG solution model for normals vs. HG
      TCC required 12/38 nuclear features yielding an AUC = 99%, sensitivity = 99%,
      specificity = 98%, PPV = 98% and NPV = 99%. The QNG solution model for LG-TCC vs.
      HG-TCC required 17/38 nuclear features, with an AUC = 99%, sensitivity = 96%,
      specificity = 97%, PPV = 97% and NPV = 96%. CONCLUSION: Computer-assisted QNG
      cell classifiers based upon the measurement of 38 nuclear features, including
      size, shape and chromatin organization, are capable of differentiating normal
      urothelial nuclei from LG-TCC and HG-TCC nuclei as well as LG-TCC from HG-TCC
      nuclei. The QNG cell classifier has shown conclusively that there are
      morphometric differences between normal urothelial and LG-TCC nuclei that may not
      be apparent to the naked eye and that it may be useful in helping the pathologist
      determine the presence or absence of LG-TCC in bladder cytology specimens.

PMID- 9513694
TI  - Thyroid cancer.

PMID- 9513695
TI  - Phototherapeutic keratectomy.
AB  - The US Food and Drug Administration recently approved the 193-nm excimer laser
      for the treatment of superficial corneal pathology and surface irregularities--a
      procedure called phototherapeutic keratectomy (PTK). Indications for PTK include
      corneal dystrophies, degenerations, and scars that impair corneal transparency,
      thus compromising visual acuity. In some cases, PTK may offer a better treatment
      modality than corneal transplant surgery. This article reviews the basic
      fundamentals of PTK, including indications for surgery, the surgical procedure,
      preoperative and postoperative patient evaluation and care, and possible
      complications.

PMID- 9513696
TI  - Phacoemulsification procedures performed with topical anesthesia.
AB  - Phacoemulsification procedures with topical anesthesia, performed with small
      corneal incisions and 4% lidocaine hydrochloride methylparaben-free eye drops,
      have very high patient satisfaction rates because patients do not experience
      intraoperative pain, do not require sutures or eye patches, and have immediate
      improvements in their vision. Phacoemulsification procedures with topical
      anesthesia are cost-effective for surgery departments because patients have
      shorter hospitalizations and require fewer chargeable items. The perioperative
      nursing role is essential to the success of phacoemulsification procedures with
      topical anesthesia.

PMID- 9513697
TI  - Surgical treatment of dacryocystitis.
AB  - Dacryocystitis is a common infection of the lacrimal sac. In adults,
      dacryocystitis results from an obstruction (ie, dacryostenosis) of the
      nasolacrimal duct. Dacryocystitis can be either an acute or chronic infection,
      and both forms usually are unilateral in nature. The hallmark symptom of both
      forms of dacryocystitis is epiphora (ie, excessive tearing). An obstruction of
      the lacrimal duct also can cause dacryocystitis. This article discusses the
      surgical treatment of dacryocystitis and provides a case study that illustrates
      perioperative nursing care of a patient who required surgical treatment of this
      lacrimal duct disorder.

PMID- 9513698
TI  - Interventional uroradiologic procedures.
AB  - Fifteen years ago, most genitourinary procedures were performed only in ORs.
      Advances in imaging and minimal access surgery (MAS) techniques offer patients a
      choice between open surgical procedures that often require lengthy hospital stays
      or interventional uroradiologic procedures that can be performed on an outpatient
      basis. Percutaneous nephrostomy procedures are one of the most common
      interventional uroradiologic procedures performed in radiology departments today.
      A percutaneous nephrostomy tube is passed under fluoroscopic guidance through the
      skin and into the renal pelvis to drain urine for patients with obstructions
      above their bladders or with strictured or nonfunctional ureters. These MAS
      procedures are safe and cost-effective and usually can be performed with i.v.
      conscious sedation and local anesthesia.

PMID- 9513699
TI  - New instrumentation allows for removal of nonpalpable breast lesions.
AB  - Breast cancer is the second leading cause of cancer deaths in women.
      Approximately 90% of breast cancer is curable if it is diagnosed and treated
      early. Increasingly, women are participating in mammographic screenings, which
      result in earlier detection of nonpalpable lesions. In the past, surgical removal
      was not an option for small lesions, and frequent mammographic monitoring was
      required until patients' lesions were large enough for needle core biopsies or
      needle localization for open surgical biopsies. Technology now has combined
      stereotactic imaging with a minimally invasive biopsy system for removal of these
      nonpalpable lesions. This capability for accurate early diagnosis and
      intervention is essential in improving patients' survival rates.

PMID- 9513700
TI  - The role of the breast clinic nurse.
AB  - Women scheduled for breast biopsy procedures experience heightened anxiety about
      the outcomes of their diagnostic procedures. Perioperative nurses have unique
      opportunities to provide quality nursing care for patients awaiting breast biopsy
      procedures and their definitive diagnoses. The prevalence (ie, 50%) of benign
      breast disease in women of reproductive age and the anxiety related to the threat
      of breast cancer are important nursing concerns. This article addresses the
      breast clinic nurse's role in meeting the emotional and informational needs of
      women scheduled for breast biopsy procedures. The human response to illness (HRI)
      model is used as a framework for understanding the phenomenon of anxiety within
      this context. The HRI model provides a basis for delivering quality nursing care
      through the development of an enhanced role for the breast clinic nurse.

PMID- 9513701
TI  - Computerization in the OR.
AB  - This article highlights the process of establishing a computerized scheduling and
      materials management system in a surgical department. The following facets of the
      computerization process are discussed: options staff members should consider when
      choosing a computer system, the importance of scheduling and inventory control,
      cost savings, how computer systems work when using electronic data interchange
      and bar coding, and case studies.

PMID- 9513702
TI  - It is time to move from the nursing process to critical thinking.
AB  - As we reflect on the concept of critical thinking in perioperative nursing
      practice, we should ask ourselves whether we think critically. If not, we must
      learn the principles of critical thinking and apply them in our clinical practice
      settings. Our perioperative nurse managers and directors must demonstrate
      critical thinking in leading other nurses in the delivery of quality, cost
      effective, service-oriented patient care. They also must identify peers who use
      critical thinking skills to support and sustain them in their quest.

PMID- 9513703
TI  - Nurses' duty to monitor patients and inform physicians.

PMID- 9513704
TI  - Qualitative and quantitative approaches to nursing research.

PMID- 9513705
TI  - Breast cancer legislation active in several states.

PMID- 9513708
TI  - Control of the three-dimensional growth pattern of mammary epithelium: role of
      genes of the Wnt and erbB families studied using reconstituted epithelium.
AB  - The mammary gland is possibly the best system in which to study the three
      dimensional organization of tissues and how that organization is disrupted in
      tumour development. The principal approach used has been to express genes such as
      oncogenes and growth factor genes in mammary epithelium in vivo, by using mammary
      specific promoters in germ-line transgenic mice; by injecting virus vectors into
      the lumen of the mammary gland; or by transplanting genetically manipulated
      mammary epithelial cells into a mammary fat pad from which the natural epithelium
      has been removed. This chapter focuses on the last approach. The Wnt genes are
      short-range signalling molecules related to Wnt-1, which was discovered as an
      oncogene in mouse mammary tumours. Several Wnt proteins are expressed in the
      mammary gland; notably, Wnt-4 is normally expressed in early pregnancy.
      Introducing Wnt-4 into the mammary epithelium of virgin mice induces a growth
      pattern very similar to that of mid-pregnancy. Wnt-4 may therefore be a local
      signal driving epithelial branching in pregnancy. ErbB/epidermal growth factor
      receptor and ErbB-2 are receptors that may be important in breast tumour
      development and normal mammary growth control. Overactive mutants of them, i.e.
      the genes v-erbB and neu, disturb the growth pattern of the mammary epithelium in
      quite distinct ways. Overactive ErbB-2 causes local development of alveoli,
      suggesting that it may be involved in normal alveolus development. The varied
      effects of these gene products show the complexity of the control of the three
      dimensional growth pattern, and encourage the idea that we may be able to relate
      oncogenic effects to normal growth controls.

PMID- 9513707
TI  - Growth and differentiation of the normal mammary gland and its tumours.
AB  - The mammary glands of non-pregnant rodents and humans consist of epithelial,
      intermediate stem and myoepithelial cells, and these have been isolated as cell
      lines in vitro. Growth factors produced by the myoepithelial cells, e.g.
      transforming growth factor alpha (TGF alpha) and basic fibroblast growth factor
      (bFGF), can stimulate the growth of the intermediate stem cells in vitro. One
      protein, p9Ka, a calcium binding regulatory protein, arises at an early stage of
      the differentiation of epithelial into myoepithelial cells in vitro and is
      associated with the cytoskeleton; another, cathepsin D, is a protease associated
      with this pathway in vivo. Unlike normal glands and benign lesions, malignant
      mammary carcinomas of rats and humans do not contain fully differentiated
      myoepithelial cells, and the resultant cell lines fail to differentiate
      completely into myoepithelial cells. Loss of the myoepithelial cells in some
      human invasive carcinomas may account, in part, for compensatory changes in the
      malignant cells. For example, overexpression of TGF alpha/ErbB-2 receptors may
      compensate for a decrease in TGF alpha, whereas ectopic production of bFGF and
      its receptors, and of p9Ka and cathepsin D, may help in tumorigenesis and in
      metastasis respectively. Thus compensation for, or retention of, molecules
      potentially involved in growth and/or differentiation by some human invasive
      carcinomas may be a mechanism by which a malignancy progresses.

PMID- 9513709
TI  - Interactions between the oestrogen and insulin-like growth factor signalling
      pathways in the control of breast epithelial cell proliferation.
AB  - There is increasing evidence for interactions between steroid and growth factor
      signalling pathways. Oestrogens modulate the responsiveness of breast epithelial
      cells to insulin-like growth factors (IGFs), and this may be the mechanism by
      which oestrogens modulate cell proliferation. Oestrogens appear to act at several
      points in the IGF signal transduction pathway. Despite earlier studies suggesting
      that breast epithelial cells do not synthesize IGF-I, we have shown by PCR that
      IGF-I is expressed and that its expression is regulated by oestrogen. IGF-II is
      expressed at markedly higher levels than IGF-I and is also regulated by
      oestrogen, consistent with it being an oestrogen-regulated autocrine growth
      factor. Oestrogens regulate the expression of IGF binding proteins and the type I
      IGF receptor. The biological significance of oestrogen regulation of IGF binding
      protein expression is not clear. Experiments in which the type I IGF receptor has
      been constitutively overexpressed have suggested that oestrogen regulation of the
      receptor is not involved in mediating the effects of oestrogen on cell
      proliferation. Recent studies have started to assess the effects of oestrogen on
      the expression of components of the IGF signal transduction pathway, and have
      shown that the expression of insulin receptor substrate-1, the principal
      substrate for the tyrosine kinase of the type I IGF receptor, is regulated by
      oestradiol.

PMID- 9513710
TI  - Transcriptional activation by oestrogen receptors.
AB  - The oestrogen receptor belongs to a superfamily of nuclear receptors that
      function as hormone-dependent transcription factors. Transcriptional activation
      is mediated by two activation regions: AF-1 in the N-terminal domain and AF-2 in
      the ligand binding domain. AF-1, whose activity is also regulated by epidermal
      growth factor and insulin-like growth factor-I, varies considerably between
      receptors, whereas AF-2 seems to be conserved in nuclear receptors. From recent
      structural analysis of the ligand binding domains of two retinoid receptors and
      the thyroid hormone receptor, it appears that this domain contains a common fold
      that generates a conserved ligand binding pocket. As a consequence of ligand
      binding, a C-terminal helix is realigned over the ligand binding pocket to form a
      novel interacting surface to which co-activators are likely to bind. Several
      candidate proteins have been identified, including receptor-interacting protein
      (RIP)-140, RIP-160, transcription intermediary factor (TIF)-1, suppressor of
      gal4D lesions (SUG)-1 and steroid receptor co-activator (SRC)-1. These proteins
      interact with receptors only in the presence of their respective hormonal
      ligands; moreover, their interaction with a series of mutant receptors correlates
      with their transcriptional activity, suggesting that they may play a role in
      transcriptional activation. However, only SRC-1 stimulates the transcriptional
      activity of receptors in transfected mammalian cells, implying that the proteins
      have different functions. The properties of RIP-140 and SRC-1 will be described
      and their potential role and mechanism of action discussed.

PMID- 9513711
TI  - Local control of mammary gland differentiation: mammary-derived growth inhibitor
      and pleiotrophin.
AB  - Mammary gland development is controlled by systemic hormones and by growth
      factors that might complement or mediate hormonal action and provide the
      signalling basis for mesenchyme-epithelial cross-talk. Two locally expressed
      factors, pleiotrophin and mammary-derived growth inhibitor (MDGI), their hormonal
      regulation and proposed functions will be discussed. Pleiotrophin expression in
      non-tumorigenic, attachment-dependent epithelial cells leads to an attachment
      independent, highly tumorigenic phenotype. The fatty acid binding protein MDGI
      specifically inhibits growth of normal mouse mammary epithelial cells, whereas
      growth of stromal cells is not suppressed. In mammary gland organ culture,
      inhibition of ductal growth by MDGI is associated with the appearance of bulbous
      alveolar end buds and formation of fully developed lobulo-alveolar structures. In
      parallel, MDGI stimulates its own epithelial-restricted expression and promotes
      milk protein synthesis. Selective inhibition of endogenous MDGI expression
      suppresses the appearance of alveolar end buds and lowers the beta-casein level
      in organ cultures. MDGI activity can be antagonized by epidermal growth factor
      (EGF); reciprocally, MDGI can suppress the mitogenic effects of EGF. An MDGI
      derived C-terminal 11-amino-acid peptide is able to mimic MDGI activity in vitro.
      In conclusion, members of the family of fatty acid binding proteins are able to
      regulate mammary gland differentiation locally, and fatty acid binding is not
      required for this activity.

PMID- 9513712
TI  - Local control of the mammary gland.
AB  - Studies on increasing the frequency of milking in dairy animals have led to the
      uncovering of the mechanism by which tactical control of the rate of milk
      secretion is achieved locally within each mammary gland, against a strategic,
      systemic control by the hormones that maintain all glands in the secretory
      condition. Experiments in vivo established that the response is local, and were
      compatible with the hypothesis that milk contains an inhibitor of its own
      secretion which accumulates during storage within the lumen of the mammary gland
      and which acts in an autocrine manner on the secretory cells. Isolation of a
      protein, initially from goats' milk, called FIL (feedback inhibitor of lactation)
      has enabled, and is enabling, further studies to be done from the whole-animal
      down to the molecular level. Examples at the whole-animal level are: the effects
      of immunization against FIL on the rate of secretion; the concentration of FIL
      and the kinetics of its formation and breakdown; the importance of the internal
      structure of the mammary gland and the capacities of the alveolar and ductular
      storage regions in determining feedback inhibition; differences between
      individuals and species influencing the degree of control exerted by FIL in
      matching supply of milk to demand by the young. Other local control mechanisms at
      the onset and cessation of lactation, including mammary distension, are also
      discussed.

PMID- 9513713
TI  - Autocrine regulation of milk secretion.
AB  - Mammary development and the rate of milk secretion are regulated by frequency and
      completeness of milk removal. This regulation occurs through chemical feedback
      inhibition by a milk constituent. Novel, immunologically related milk proteins
      able to perform this function have been isolated from caprine, bovine and human
      milk, based on their ability to inhibit milk constituent synthesis in mammary
      tissue and cell cultures, and to decrease temporarily milk secretion when added
      to milk stored in the mammary gland. Inhibition is concentration-dependent,
      suggesting that milk accumulation and removal is accompanied by cyclical changes
      in inhibitor accretion and depletion in milk. Feedback inhibition is an autocrine
      mechanism: the caprine inhibitor, termed FIL (feedback inhibitor of lactation) is
      synthesized by mammary epithelial cells in primary culture. Inhibition is by
      reversible blockade of the secretory pathway, an effect which, by down-regulating
      cell-surface hormone receptors, has longer-term consequences on epithelial cell
      differentiation. Treatment of goat mammary epithelial cell cultures with caprine
      FIL initially decreased milk protein secretion and subsequently reduced milk
      protein messenger RNA abundance. Thus the actions of a single milk constituent
      can bring about both the effect of milking frequency on milk secretion rate and a
      sequential modulation of cellular differentiation which acts to sustain the
      secretory response. Long-term regulation, through changes in galactopoietic
      hormone receptors, also provides an efficient mechanism for integrating acute
      intramammary regulation of lactation with strategic endocrine control of mammary
      tissue development.

PMID- 9513714
TI  - Role of calcium in the pathway for milk protein secretion and possible relevance
      for mammary gland physiology.
AB  - In an attempt to define control points within the secretory pathway for casein
      synthesis and secretion, we have examined the role of both cytosolic and intra
      organelle Ca2+ in the control of casein synthesis, phosphorylation and secretion.
      In addition, the possible role of cell volume changes in stretch-activation of
      Ca2+ signals was examined. Examination of the kinetics of casein secretion from
      freshly isolated lactating mouse mammary acini showed that a portion of the newly
      synthesized casein was secreted in a constitutive manner. A further portion
      remained within the cells, and this was released following elevation of the
      intracellular free calcium concentration ([Ca2+]i) using ionomycin, indicating
      the presence of a Ca(2+)-regulated pathway for casein release. An increase in
      [Ca2+]i occurred in response to hypotonic challenge to induce cell swelling, and
      this involved both Ca2+ entry and Ca2+ mobilization from intracellular stores.
      Experiments examining the effects of depletion of intra-organelle Ca2+ indicated
      that intra-organelle Ca2+ was required for maintained casein phosphorylation, but
      not its secretion. Depletion of Ca2+ from the endoplasmic reticulum led to a
      marked inhibition of casein synthesis. The possible significance of these control
      mechanisms for the physiology of the mammary gland is discussed.

PMID- 9513715
TI  - Composite response elements mediate hormonal and developmental regulation of milk
      protein gene expression.
AB  - Our laboratory has been studying the mechanisms by which hormones regulate the
      expression of differentiated function in the normal mammary gland and how these
      regulatory mechanisms have deviated in breast cancer. Two rat milk protein genes,
      encoding beta-casein and whey acidic protein, have been employed as molecular
      markers of mammary epithelial cell differentiation. Composite response elements
      containing multiple binding sites for several transcription factors mediate the
      hormonal and developmental regulation of milk protein gene expression. In the
      whey protein gene promoters, these include binding sites for nuclear factor (NF)
      I, as well as the glucocorticoid receptor (GR) and signal transducers and
      activators of transcription (Stat5). In the casein promoters, these include
      binding sites for Stat5, Yin Yang 1 (YY1), GR and the CCAAT/enhancer binding
      protein (C/EBP). The C/EBP family of DNA binding proteins may play a pivotal role
      in maintaining the balance between cell proliferation and terminal
      differentiation in mammary epithelial cells. During normal mammary gland
      development, expression of LIP (liver-enriched inhibitory protein, a dominant
      negative isoform of C/EBP beta) is hormonally regulated and correlates with cell
      proliferation during pregnancy. LIP can form heterodimers with other C/EBP family
      members and suppress their transcriptional activity. In contrast, C/EBP alpha is
      predominantly expressed during lactation following terminal differentiation.
      Elevated LIP levels have been detected in mouse, rat and human breast tumours of
      different aetiologies. This provides a mechanism, therefore, to block terminal
      differentiation and facilitate continued proliferation.

PMID- 9513716
TI  - Regulation of gene expression in mammary epithelial cells by cellular confluence
      and sequence-specific DNA binding factors.
AB  - Milk protein gene expression in mammary epithelial cells is regulated by
      interactions of the cells with each other and with extracellular-matrix
      components, and by the lactogenic hormones. Cell-cell and cell-extracellular
      matrix interactions confer a state of competence to HC11 mammary epithelial
      cells. Cellular confluence and matrix deposition are prerequisites for the
      lactogenic hormone induction of, for example, beta-casein synthesis. We have
      studied how these cellular interactions influence transcription factor activity.
      Proximal and distal regulatory elements have been identified in the DNA of the
      beta-casein gene promoter that confer transcriptional induction to the lactogenic
      hormones in competent cells. A region located between positions -221 and -170 of
      the rat beta-casein promoter contains overlapping binding sites for DNA binding
      factors with positive and negative regulatory activity. A construct containing
      221 nt of 5' promoter sequences linked to a chloramphenicol acetyltransferase
      (CAT) reporter gene and transfected into HC11 cells has low constitutive
      expression and is strongly inducible. Deletion of the sequences to -183 results
      in an increase in both constitutive and induced expression. Mutations in or
      deletion of the region from -183 to -170 abolish promoter activity. A sequence
      specific single-stranded DNA binding transcriptional repressor (STR), composed of
      two proteins, binds to the upper strand of the -194 to -163 fragment and
      negatively regulates transcription. STR also recognizes the 5' untranslated
      region of the beta-casein mRNA and is sequestered into the cytoplasm by RNA after
      lactogenic hormone induction. Sequestration by RNA allows an activator to bind to
      the fragment -183 to -170. This activator has been identified as SARP, a sequence
      specific single-stranded DNA activator region binding protein. The binding site
      of SARP is found both in the upper and the lower strands of this fragment. SARP
      has no affinity for RNA. It enhances transcription of a promoter construct
      containing rat beta-casein promoter sequences from -183 to -1 and of a
      heterologous promoter containing multimerized copies of the -194 to -163 fragment
      in a lactogenic-hormone-independent manner. Mutations between positions -183 and 
      170, which result in a loss of promoter activity, also prevent SARP from binding
      to the DNA. Confluence of HC11 cells up-regulates the DNA binding activity of
      SARP. High SARP activity is also detected in mammary gland cells of lactating
      mice and is regulated by suckling. Withdrawal of pups from their lactating
      mothers results in a rapid decrease of SARP activity. We have purified SARP from
      the lactating mammary tissue of sheep and have identified proteins of 28 and 35
      kDa.

PMID- 9513717
TI  - Gene expression in the mammary glands of transgenic animals.
AB  - The gene encoding the milk protein beta-lactoglobulin in sheep is expressed in
      the mammary gland in a tissue-specific manner during pregnancy and lactation. The
      unmodified sheep gene behaves appropriately in transgenic mice, and we have shown
      that many of the cis-acting elements that mediate this pattern of expression are
      located in the proximal 400 bp of the promotor. Using a combination of approaches
      we have identified a number of discrete cis-acting elements and their
      corresponding trans-acting factors that control the responsiveness of this gene
      in vivo. The beta-lactoglobulin promoter elements can be used to target the
      expression of foreign genes to the mammary gland in transgenic mice. We have used
      this approach in basic studies of mammary gland biology and for the production of
      therapeutic proteins in the milk of transgenic animals. In these circumstances,
      however, the promoter rarely functions optimally, and it may even be silenced;
      consequently, we have had to develop a number of strategies to overcome this
      problem. Nevertheless, foreign proteins do appear to be appropriately post
      translationally modified when they are expressed in the mammary gland.

PMID- 9513718
TI  - Production of therapeutic proteins in the milk of transgenic livestock.
AB  - With the advent of the Human Genome Project and associated developments in
      'functional genomics', there are going to be increasing numbers of proteins
      identified and developed for clinical use. There are a number of production
      methods available, although only three, bacterial, yeast and mammalian cell
      culture, have produced recombinant proteins that have been approved for clinical
      use. Nevertheless other production systems are under development, and one, the
      production of human proteins in the milk of transgenic livestock, is showing
      great promise, with two proteins now in clinical trials. This chapter will
      compare and contrast the various competing technologies and will then concentrate
      on factors influencing the choice and use of the transgenic system.

PMID- 9513719
TI  - Oncogenic activation of Neu/ErbB-2 in a transgenic mouse model for breast cancer.
AB  - Recent evidence has suggested that amplification and overexpression of erbB-2/neu
      is an important determinant in the initiation and progression of human breast
      cancer. Consistent with this assertion is the observation that transgenic mice
      that overexpress the neu proto-oncogene heritably develop mammary
      adenocarcinomas. More recently, we have demonstrated that activation of neu in
      many of these tumours occurs as a result of somatic mutations located within the
      transgene itself. Indeed, careful examination of the altered neu transcripts
      revealed the presence of in-frame deletions that encode aberrant Neu receptors
      lacking 5-12 amino acids within the extracellular domain, located adjacent to the
      transmembrane domain. Interestingly, the majority of the deletions analysed
      affect one of several conserved cysteine residues present within this region.
      Moreover, introduction of these activating mutations into the wild-type neu cDNA
      results in its oncogenic conversion. These observations suggest that this
      cysteine-rich region plays an important role in regulating the catalytic activity
      of Neu.

PMID- 9513720
TI  - Use of mouse mammary tumour virus (MMTV)/neu transgenic mice to identify genes
      collaborating with the c-erbB-2 oncogene in mammary tumour development.
AB  - Mouse mammary tumour virus (MMTV)/neu transgenic mice develop clonal or
      oligoclonal mammary tumours stochastically. The pathology of these tumours is
      very similar to that of human breast tumours. Moreover, these mouse tumours
      metastasize in the lungs. We present evidence that this mouse model of human
      breast tumours can be instrumental in identifying novel genes of two distinct
      classes (activated oncogenes or tumour suppressor genes) which may collaborate
      with the c-erbB-2/neu transgenic oncogene.

PMID- 9513721
TI  - Induction of a variety of preneoplasias and tumours in the mammary glands of
      transgenic rats.
AB  - Although transgenic mouse models for breast cancer have frequently been reported
      in the literature, transgenic rat models have not been described. We have
      generated transgenic rats overexpressing the human transforming growth factor
      alpha (TGF alpha) and c-erbB-2 genes in the mammary gland under the control of
      the mouse mammary tumour virus (MMTV) long terminal repeat promoter, and have
      analysed multiple lines of these rats to the second (F2) generation. Female
      MMTV/TGF alpha rats frequently develop severe hyperplasias during pregnancy, and
      a variety of tumours of long latency. The mammary glands of MMTV/TGF alpha rats
      fail to involute fully after the completion of lactation. Expression of the TGF
      alpha transgene is highest in the hyperplasias. MMTV/c-erbB-2 female rats develop
      a spectrum of benign and malignant lesions, including ductal carcinoma in situ
      and carcinomas. Expression of the c-erbB-2 transgene is found in benign tumours
      such as fibroadenomas, but is highest in the carcinomas. These animals model a
      spectrum of lesions found in human breasts and suggest that TGF alpha
      overexpression can act at a relatively early stage in the pathogenesis of breast
      cancer in the rat, resulting in a predominantly hyperplastic response, whereas
      overexpression of c-erbB-2 plays a role in the induction of various benign
      lesions and more advanced breast carcinomas.

PMID- 9513722
TI  - Impact of molecular biology on the clinical management of breast cancer.
AB  - The use of molecular markers is being explored in the prediction of risk of
      developing breast cancer, in the assessment of prognosis and in the
      identification of appropriate treatment. Rational selection of treatment for a
      patient requires an accurate assessment of the prognosis and prediction of the
      response to a given treatment. Neither of these is possible with current
      clinicopathological markers. As a result, the current management of breast cancer
      is empirical, based on the outcome of randomized clinical trials that examine
      average effects within populations. Clinicopathological factors can be used to
      separate patients into broad prognostic groups, and treatment decisions are made
      on this basis. With this approach up to 70% of patients receive adjuvant
      treatment that is either unnecessary or ineffective. Molecular biological markers
      have the potential to improve this situation. A wide range of markers have been
      shown to be predictors of prognosis, but added individually to current prognostic
      indicators they do not improve the functional accuracy of prognosis or response
      prediction. There is a need for a molecular prognostic index that combines the
      results of a number of markers and can be used in conjunction with a clinical
      index to produce a more useful prognosis. There is also a need for an index that
      will predict responses to specific treatments. The impact of molecular biology on
      clinical management is a revolution waiting to happen.

PMID- 9513723
TI  - Type I growth factor receptors: current status and future work.
AB  - The type 1 family of growth factor receptors consists of the epidermal growth
      factor receptor (EGFR), and ErbB-2, ErbB-3 and ErbB-4. Six ligands are known to
      bind directly to EGFR, none (at present) to ErbB-2, and a family of ligands
      collectively called the neuregulins bind to both ErbB-3 and ErbB-4. It is now
      apparent that the receptors function in various heterodimeric pairs, depending on
      their concentrations, the concentrations of particular ligands in the environment
      and some intrinsic degree of dimer selectivity. Overexpression of EGFR, ErbB-2
      and ErbB-3 has been found commonly in solid human tumours. ErbB-4 has not yet
      been examined. The EGFR is also activated by various mutations in brain tumours
      and possibly in other tumour types. These changes appear to be one of the causes
      of malignant transformation. They may also provide information regarding the
      course of disease and response to current treatments. Finally, they are targets
      for a variety of new forms of treatment being developed in the laboratory, in
      preclinical models and in a few cases in clinical trials.

PMID- 9513724
TI  - Role of epidermal growth factor receptor family members in growth and
      differentiation of breast carcinoma.
AB  - Members of the epidermal growth factor (EGF) family of tyrosine kinase receptors
      are involved in the regulation of cell growth and differentiation, and are found
      to be expressed in many types of cancers. Activation of these receptors can be
      elicited by multiple ligands, resulting in the formation of a spectrum of
      heterodimer complexes and a number of biological outcomes. A clear demonstration
      of biological activation by a single complex has been difficult to address
      because of the endogenous expression of HERs (human EGF-like receptors) in many
      cell lines. We have generated a collection of cell lines expressing all HERs
      alone or in all pairwise combinations in a clone of NIH 3T3 cells (3T3-7d) devoid
      of detectable EGF receptor family members. Transformation, as measured by growth
      in soft agar, only occurred in cells expressing two different HER family members.
      Transformation with activated Neu and the rate of in vivo tumour formation were
      also correlated with the expression of multiple HERs in the same cell. To further
      our understanding of the role of heterodimer signalling, we demonstrated that,
      within a breast carcinoma cell line, activation of HER-3 results in cellular
      differentiation, prolonged activation of extracellular-signal-related kinase 1
      (ERK1) activity and an increase in p21CIP1/WAF1 nuclear staining. In contrast,
      activation of HER-4 is mitogenic, induces transient activation of ERK1 activity
      and decreases the nuclear staining of p21CIP1/WAF1. These differences in
      biochemical and biological responses are correlated with the contrasting
      abilities of HER-3 and HER-4 to be down-regulated from the cell surface. The cell
      surface localization of HER-3 does not change in response to ligand, whereas
      activation of HER-4 results in a loss of cell-surface staining followed by
      accumulation into a perinuclear compartment.

PMID- 9513725
TI  - Somatic mutations that contribute to breast cancer.
AB  - Cytogenetic and molecular analyses of primary sporadic human breast carcinomas
      have documented at least 12 different chromosome arms affected by loss of
      heterozygosity (LOH). This has been taken as evidence for the presence of
      putative tumour suppressor genes in the remaining allele within the affected
      regions. We have previously identified three regions on chromosome 17q that are
      affected by LOH in primary human breast tumours. A physical map of one of these
      regions (17q21) has been prepared. The putative target gene appears to be located
      between the D17S846 and D17S746 loci. We are currently determining whether either
      of two genes located in this region is the target for LOH. The mouse mammary
      tumour model system provides an approach for identifying genes which, when
      activated or inactivated by mouse mammary tumour virus (MMTV) integration,
      contribute to specific stages of mammary tumorigenesis. Using this approach we
      have identified two genes, designated NOTCH4/INT3 and INT6 respectively.
      Interruption of NOTCH4/INT3 by MMTV represents a gain-of-function mutation that
      has profound consequences for mammary gland development and tumorigenesis. INT6
      was found to be interrupted by an integrated MMTV genome in a mammary
      hyperplastic outgrowth line and two independent mammary tumours. In each case the
      transcriptional orientation of the viral genome was opposite to that of INT6. The
      rearranged allele was expressed as a truncated chimaeric RNA species composed of
      INT6 coding sequences, intron sequences and MMTV sequences. Since the non
      rearranged allele contained no mutations, we conclude that MMTV integration into
      INT6 causes a dominant-negative mutation or biologically activates its function.
      The nucleotide sequence of INT6 is unrelated to any of the known genes in the
      GenBank database, but is evolutionarily highly conserved.

PMID- 9513726
TI  - Inherited predisposition to breast cancer.
AB  - Breast and ovarian cancers sometimes occur in families. Linkage studies in these
      families have led to the mapping and then cloning of two predisposing genes,
      BRCA1 and BRCA2. Together these genes probably account for rather less than 5% of
      all breast and ovarian cancers. In the medium term, understanding the function of
      the proteins encoded by these genes should lead to a better understanding of how
      the cancers develop, and the design of new approaches to treatment and
      prevention. Of more immediate concern is the possibility of genetic testing for
      cancer susceptibility in families. In multiple-case families, where the BRCA1 or
      BRCA2 mutation is likely to be present and there are clear clinical decisions to
      be taken, genetic testing is not controversial. The costs and benefits of wider
      testing are much less clear.

PMID- 9513727
TI  - Breast cancer metastasis-associated genes: role in tumour progression to the
      metastatic state.
AB  - Breast cancer patients usually do not die of their primary cancers; they die of
      metastatic disease. Thus understanding the progression of breast cancer to the
      metastatic state and the changes that take place in highly malignant breast cells
      are important goals that could eventually result in new therapeutic approaches to
      highly progressive breast disease. Changes in the expression of certain genes or
      alterations in gene structures and encoded products can result in benign tumour
      cells progressing to the metastatic state. Experimentally, this has been
      performed by transferring dominantly acting oncogenes into susceptible cells and
      then testing the malignant properties of these cells in suitable animal models,
      but such rapid qualitative changes occur in vivo only rarely, and the natural
      progression of mammary cells to the metastatic state is thought to occur through
      a slow stepwise process that can take several years. Some of the slow stepwise
      changes in mammary cancer progression can be reversible and need not involve
      dominantly acting oncogenes or tumour suppressor genes, consistent with clinical
      observations. An important element of the natural progression of mammary tumours
      to malignancy may be their ability to circumvent microenvironmental controls that
      regulate growth and cellular diversity, a process that appears to involve mainly
      quantitative changes in gene expression, resulting in loss of normal cellular
      regulation. One of the important mechanisms of cellular regulation in epithelial
      tissues, such as those found in the breast, is mediated by intercellular
      junctional communication. Alterations in gene expression can result in loss of
      gap-junctional communication, concomitant with cellular diversification and
      progression. It is thought that the highly malignant cancer cells that have
      slowly evolved in vivo with only a few qualitative changes in gene structure have
      undergone extensive cycles of diversification and the accumulation of several
      quantitative changes in the expression of various genes that encode products
      related to malignancy. We have identified some of the genes that are related to
      progression and metastasis in breast cancer. For example, one of these genes, a
      novel gene called mta1 (in rodents) or MTA1 (in humans) appears to be involved in
      mammary cell motility and growth regulation. Thus highly malignant cellular
      phenotypes can arise rapidly due to specific qualitative changes in critical
      controlling genes, or more slowly via less critical qualitative genetic changes
      coupled with other cellular changes, such as loss of intercellular communication,
      and changes in gene expression, such as in the MTA1 gene, resulting in cellular
      diversification and ultimately tumour progression to the metastatic state.

PMID- 9513728
TI  - Adhesion molecules in breast cancer: role of alpha 2 beta 1 integrin.
AB  - An early event in the development of breast carcinomas is the loss of normal
      tissue architecture. In benign lesions and in situ tumours both luminal and
      myoepithelial cells are present, but in most invasive cancers the malignant cell
      has the phenotype of the luminal cell, and proliferates without contacting the
      myoepithelial cells or the basement membrane. The reduction in cell contacts is
      clearly crucial for the initiation of metastatic growth, and is accompanied by a
      loss of expression or function of cell adhesion molecules. Immunohistochemical
      studies using tissue and tumour sections indicate that a decrease in the level of
      expression of the alpha 2 beta 1 integrin is observed in many breast cancers. A
      specific and crucial role for this molecule in the maintenance of normal
      morphological differentiation has also been demonstrated in in vitro studies. The
      evidence from these studies suggests that, in mammary epithelial cells, oncogenes
      may be upstream regulators of the expression of the alpha 2 beta 1 integrin and
      of other specific molecules important for epithelial differentiation. These
      findings implicate oncogenes in the initial events relating to the disruption of
      tissue architecture that is seen in invasive breast cancer.

PMID- 9513729
TI  - Nm23 and tumour metastasis: basic and translational advances.
AB  - The nm23 genes were discovered on the basis of their reduced expression by highly
      metastatic cell lines. This trend was confirmed in cohorts of several types of
      human carcinomas and melanomas. Several transfection studies have demonstrated
      the suppressive effect of nm23 overexpression on the metastatic aggressiveness of
      melanoma and breast carcinoma cells in vivo. These transfection experiments have
      also demonstrated an effect of nm23 overexpression on cellular functions involved
      in the metastatic phenotype, such as cell motility, and point to a regulatory
      role for Nm23 proteins in cellular signalling pathways. Nm23 homologues from
      various species are also involved in normal tissue development and
      differentiation. Transfection of nm23-H1 into breast cancer cells provided a
      functional demonstration of the involvement of this gene in the differentiation
      of mammary epithelial cells. However, the molecular mechanism of these biological
      effects remains unknown. Several biochemical activities have been reported for
      Nm23, including NDP kinase activity, serine autophosphorylation and protein
      histidine kinase activity. To define the possible significance of these
      biochemical activities, we carried out site-directed mutagenesis of the relevant
      codons of nm23-H1 cDNA and studied the effects upon transfection into MDA-MB-435
      human breast carcinoma cells. We have also used Nm23 expression as a molecular
      marker to identify novel compounds that are active against the most aggressive
      tumour cells. This approach revealed that none of the standard agents currently
      in clinical use is preferentially active against the most aggressive tumour
      cells, and allowed us to identify new compounds that are preferentially
      inhibitory towards low-Nm23-expressing breast carcinoma and melanoma cell lines.
      This analysis also revealed a significant correlation between Nm23 levels and
      sensitivity of the tumour cells to alkylating agents. A functional implication of
      Nm23 proteins in this phenomenon was demonstrated after transfection of nm23
      cDNAs into melanoma and breast and ovarian carcinoma cells.

PMID- 9513730
TI  - Use of DNA transfer in the induction of metastasis in experimental mammary
      systems.
AB  - The metastatic spread of cancer is a little understood process, in part because
      it is difficult to model the entire process using experimental approaches in
      vitro. The ability to transfer DNA into non-metastatic mammary cells and to
      observe the induction of metastasis in vivo provides a means for identifying DNA
      sequences that are associated with the development of metastatic capability.
      Using these techniques, a metastasis-associated cytoskeletal calcium binding
      protein, S100A4 (p9Ka), has been identified as an inducer of metastatic
      capability in benign rat mammary epithelial cells. Metastasis can also be induced
      in the rat mammary epithelial cells by fragments of DNA from metastatic, but not
      from benign, human breast tumour cells. These non-coding fragments of DNA act via
      the induction of osteopontin, an extracellular, integrin binding, calcium binding
      protein. Since both osteopontin and S100A4 are thought to be associated with
      malignancy in human breast cancer specimens, gene transfer techniques can
      identify genes for metastasis-inducing proteins that may play a role in breast
      cancer, and further suggest that cell migration/motility might be important in
      the metastatic process.

PMID- 9513731
TI  - Matrix metalloproteinases and metastatic cancer.
AB  - The rationale for matrix metalloproteinase (MMP) inhibition as a means to treat
      disease progression in breast cancer stems from the apparent involvement of MMPs
      in the hydrolysis of basement membranes during tumour cell invasion and
      subsequent metastasis. MMP-mediated matrix remodelling also appears to promote
      the growth of tumour cells, possibly by facilitating the proliferation and
      migration of endothelial cells and the neovascularization of tumour tissue. We
      found that transfection of the C127 breast cancer cell line by MMP-2 (gelatinase
      A), but not by MMP-1 or MMP-3 (collagenase and stromelysin respectively), gave
      rise to an invasive and metastatic phenotype. We were surprised to find that this
      phenotype depended not only on the catalytic properties of MMP-2 but also on
      properties associated with the MMP-2 non-catalytic C-terminal domain. Experiments
      with a synthetic gelatinase inhibitor revealed that a single dose could prevent
      the lungs of nude mice being colonized by the MMP-2 transfectants, and that the
      inhibitor had to be administered during or shortly after injection of the cells,
      indicating that an early event, such as the extravasation of the cells into the
      lung, is gelatinase-dependent in this system. In other studies employing long
      term treatment with CT1746, an orally active gelatinase inhibitor, we have
      previously demonstrated a reduction in primary tumour growth rates, localized
      spread, and spontaneous metastasis, even when the treatment was commenced several
      days after tumour implantation. Furthermore, additive effects were recorded when
      gelatinase inhibitor therapy was combined with cytotoxic drug treatment. Since
      the gelatinase inhibitors can also inhibit bone resorption in vitro, these
      observations point to their potential for delaying disease recurrence and
      reducing rates of bone loss following conventional therapeutic strategies, in
      metastatic breast cancer.

PMID- 9513732
TI  - Altered levels of the synaptosomal associated protein SNAP-25 in schizophrenia.
AB  - BACKGROUND: Identifying brain changes in schizophrenia has been a major research
      focus for many years. Although impressive gains have been made in neuroimaging
      and brain electrophysiology, molecular and cellular markers of schizophrenia have
      lagged. There are no consistent biochemical markers for schizophrenia
      pathophysiology and none that reflect treatment course. METHODS: Samples were
      obtained from 25 postmortem schizophrenic brains and 31 nonschizophrenic
      controls. These samples were processed, and the synaptosomal fraction was
      isolated. Ten micrograms of protein from each of these samples was solubilized in
      a sodium dodecylsulfate sample buffer and separated on 10% (wt/vol)
      polyacrylamide gels. Monoclonal antibody (SMI-81) was incubated with the blots
      and, using quantitative Western blotting, we measured the relative amounts of
      SNAP-25 in these samples. RESULTS: We report altered levels of SNAP-25 in both
      the inferior temporal cortex (Brodmann area 20) and prefrontal association cortex
      (Brodmann areas 9 and 10) in postmortem brains of patients with schizophrenia
      relative to nonschizophrenic controls. Normal levels of SNAP-25 are noted in
      schizophrenics in area 17, decreased levels in areas 10 and 20, and an elevated
      level in area 9. CONCLUSIONS: These data support cytoarchitectural observations
      that the cerebral cortex of schizophrenic patients has extensive pathology. The
      data presented here, along with data on other brain-specific proteins, indicate a
      complicated molecular adaptation to the causative factors of schizophrenia.

PMID- 9513733
TI  - Abnormalities of auditory event-related potentials in schizophrenia prior to
      treatment.
AB  - BACKGROUND: P300 amplitude reduction is a consistent finding in schizophrenic
      patients, but it is unclear if this abnormality predates neuroleptic treatment or
      is present at onset of illness. METHODS: Auditory event-related potentials
      (ERPs), during a standard oddball paradigm, were recorded from 45 neuroleptic
      naive schizophrenics, 56 drug-free, previously treated schizophrenics, and 73
      healthy normal controls. Forty-seven of the schizophrenic subjects had their
      first episode within the past year. RESULTS: N200 amplitude did not differ among
      groups. P300 amplitude was significantly smaller in both neuroleptic-naive and
      previously treated schizophrenic groups compared to the control groups. There
      were no significant differences between the two schizophrenic groups in P300
      amplitude. N200 and P300 latency were prolonged in previously treated
      schizophrenics compared to neuroleptic-naive schizophrenics and normal controls.
      CONCLUSIONS: The present study suggests that ERP abnormalities, especially P300
      amplitude reduction, are already present prior to the administration of
      neuroleptic medication in the earliest stage of schizophrenia.

PMID- 9513734
TI  - Asymmetrical changes in the fodrin alpha subunit in the superior temporal
      cortices in schizophrenia.
AB  - BACKGROUND: We examined possible abnormalities in neural structural proteins that
      may underlie morphometric changes reported in the left superior temporal cortices
      (Brodmann's area 22) of schizophrenics. METHODS: Particulate proteins of the
      superior temporal cortices taken at autopsy from 11 schizophrenic and 9 control
      brains were fractionated by gel electrophoresis. Target proteins, identified by
      reading their amino acid sequences, were immunoquantified using the specific
      antibody. RESULTS: Amino acid sequences of the 150-kDa proteins on sodium dodecyl
      sulfate/polyacrylamide gel electrophoresis, which were significantly increased on
      the left side of schizophrenic superior temporal cortices, revealed that they
      were proteolytic fragments of the alpha subunit of fodrin, a major cytoskeletal
      protein underlying the plasma membrane. Immunoquantification using the specific
      antibodies against alpha and beta subunits of fodrin indicated that there exist
      concomitant decreases in the full-length 240-kDa form and increases in the 150
      kDa form of alpha-fodrin with no changes of the 235-kDa form of beta-fodrin in
      the left superior temporal cortices of the schizophrenic brains. CONCLUSIONS: The
      findings may be a possible molecular basis for linking morphometric changes to
      neurochemical pathophysiology in schizophrenia.

PMID- 9513735
TI  - Frontal lobe of children with schizophrenia spectrum disorders: a proton magnetic
      resonance spectroscopic study.
AB  - BACKGROUND: Schizophrenia is commonly considered a neurodevelopmental disorder.
      Our aim was to determine whether the proton magnetic resonance spectroscopic (1H
      MRS) changes seen in adults with schizophrenia are displayed in children at risk
      for developing schizophrenia. METHODS: Children with symptoms of schizophrenia
      spectrum disorders (n = 16; mean age = 132 months) and a comparison group (n =
      12; mean age 130 months) took part in a 1H-MRS study of the left frontal lobe.
      Areas of peaks from N-acetylaspartate (NAA), choline (Cho), and creatine (Cre)
      were determined and ratios of NAA/Cre and Cho/Cre calculated and compared between
      groups. RESULTS: The mean ratio of NAA/Cre was significantly lower in
      schizophrenia-spectrum subjects than the comparison group (1.67 vs. 1.92; p <
      .05). Medication status did not affect results in schizophrenia-spectrum
      subjects. CONCLUSIONS: Our findings suggest that the metabolic changes associated
      with adult schizophrenia are observed in children with some or all of the
      symptoms of schizophrenia, supporting a neurodevelopmental theory for
      schizophrenia.

PMID- 9513736
TI  - Plasma oxytocin levels in autistic children.
AB  - BACKGROUND: Social impairments are central to the syndrome of autism. The
      neuropeptide oxytocin (OT) has been implicated in the regulation of social
      behavior in animals but has not yet been examined in autistic subjects. METHODS:
      To determine whether autistic children have abnormalities in OT, midday plasma
      samples from 29 autistic and 30 age-matched normal children, all prepubertal,
      were analyzed by radioimmunoassay for levels of OT. RESULTS: Despite individual
      variability and overlapping group distributions, the autistic group had
      significantly lower plasma OT levels than the normal group. OT increased with age
      in the normal but not the autistic children. Elevated OT was associated with
      higher scores on social and developmental measures for the normal children, but
      was associated with lower scores for the autistic children. These relationships
      were strongest in a subset of autistic children identified as aloof. CONCLUSIONS:
      Although making inferences to central OT functioning from peripheral measurement
      is difficult, the data suggest that OT abnormalities may exist in autism, and
      that more direct investigation of central nervous system OT function is
      warranted.

PMID- 9513737
TI  - Plasma homovanillic acid and the dopamine transporter during cocaine withdrawal.
AB  - BACKGROUND: Plasma homovanillic acid (HVA) has been used as a measure of central
      dopaminergic activity but the validity of this method continues to be
      investigated. We used single photon emission tomography (SPECT) assessment of the
      dopamine (DA) transporter for comparison with plasma HVA in subjects at varying
      stages of abstinence from cocaine. METHODS: Nineteen subjects were studied in two
      separate treatment sites. Plasma HVA and methoxyhydroxyphenethyleneglycol (MHPG)
      were measured by gas chromatography-mass spectroscopy (GC-MS). The DA transporter
      was quantified using the SPECT ligand [123I]B-CIT. RESULTS: At 2 weeks of
      abstinence and beyond there was an increasing positive correlation between plasma
      HVA and the SPECT measurement of the DA transporter (V3"). CONCLUSIONS: Plasma
      HVA may be more likely to reflect DA transporter density in the striatum when
      there is not a major drug-related change in the DA system.

PMID- 9513738
TI  - An electroencephalographic study comparing maximum blink rates in schizophrenic
      and nonschizophrenic psychiatric patients and nonpsychiatric control subjects.
AB  - BACKGROUND: We did a retrospective electroencephalographic (EEG) analysis of
      blink rates in patients with psychiatric disorders and control subjects to
      determine whether maximum blink rates under different conditions were higher in
      patients with psychiatric disorders. METHODS: Maximum blink rates in those with
      schizophrenia (n = 23), those with nonschizophrenic psychiatric illnesses (n =
      21), and nonpsychiatric control subjects (n = 35) were obtained from patients'
      EEGs and compared with one-way analysis of variance and post hoc tests. In
      addition, correlation analysis was performed to determine if patients'
      medications affected maximum blink rates. RESULTS: Patients with schizophrenic
      and nonschizophrenic psychiatric disorders had twofold higher maximum resting
      blink rates compared to controls (p < .05 respectively). No difference was found
      between those with schizophrenic and nonschizophrenic psychiatric disorders. The
      maximum blink rate during cognitive testing was also twofold higher in those with
      nonschizophrenic psychiatric disorders (n = 11) compared to controls (n = 16; p <
      .05). Within each group, maximum blink rates during quiet rest and cognitive
      testing did not differ, nor were there differences between groups in the duration
      of high-frequency blinking (greater than 40 blinks per minute) during quiet rest.
      In psychiatric patients, none of the medications taken at the time of EEG
      recording correlated with maximum blink rates. CONCLUSIONS: High maximum blink
      rates recorded by EEG may suggest the presence of a psychiatric disorder.

PMID- 9513739
TI  - Recurrence pattern of serum creatine phosphokinase levels in repeated acute
      psychosis.
AB  - BACKGROUND: Elevated serum creatine phosphokinase (CPK)MM level is frequently
      found in acute psychosis. Theories relate this CPKemia to psychomotor agitation
      and medication. We hypothesized that psychosis-related CPKemia observed in
      individual patients is relatively consistent. METHODS: Ninety psychotic patients
      were studied; 83% were schizophrenics (Brief Psychiatric Rating Scale scores > or
      = 40) whose serum CPKMM levels were recorded during two or more different acute
      psychoses. The serum CPKMM levels used were the maximal levels monitored during
      the beginning of each hospitalization. The last CPK measurement in a
      circumscribed period was defined as the index serum CPK level (IndCPK). The mean
      of all other individual maximal CPK measurements during other psychotic episodes
      was defined as the average CPK (AvgCPK). RESULTS: Multiple linear regression
      analysis showed a significant correlation of natural logarithm (Ln) of (IndCPK
      with Ln(AvgCPK), as well as with gender (coefficient = .65 and .63, p < .0001 and
      p < .01, respectively). There were significantly higher IndCPK levels among male
      patients than among female patients (p < or = .001). A relatively consistent
      individual pattern of serum CPKMM levels during repeated acute psychotic episodes
      was observed. CONCLUSIONS: Serum CPKMM levels and gender were found to be good
      predictors of maximal serum CPKMM levels during every repeated acute psychotic
      episode. High IndCPK levels are probably risk factors for neuroleptic malignant
      syndrome.

PMID- 9513740
TI  - Core body temperature is normal in chronic fatigue syndrome.
AB  - BACKGROUND: Subjects with chronic fatigue syndrome (CFS) frequently report
      symptoms of subnormal body temperature and low-grade fever. We conducted a study
      to determine whether CFS subjects manifest any abnormality of core body
      temperature (CBT) that might help explain their fatigue. METHODS: Continuous 24
      hour recordings of CBT measured every 5 min were performed in 7 subjects meeting
      the Centers for Disease Control definition of CFS. Three additional groups were
      studied: normal controls, subjects with seasonal allergy, and subjects with major
      depression. Subjects (n = 7) in each group were age-, sex-, and weight-matched to
      the CFS group and had normal basal metabolic rates, thyroid function, and 24-hour
      urinary free cortisol excretions. CBT was measured with an ingestible radio
      frequency transmitter pill and a belt-worn receiver-logger. Each pill was factory
      calibrated to +/- 0.1 degree C and field-calibrated with a water bath calibration
      prior to use. RESULTS: The 24-hour mean calibration-adjusted CBTs of each group
      were not significantly different (control: 37.00 +/- 0.17 degrees C; CFS: 37.04
      +/- 0.31 degrees C; allergy: 37.15 +/- 0.18 degrees C; depression: 37.16 +/- 0.18
      degrees C). Similarly, the mean peak and trough circadian temperatures were not
      statistically different. The mean 24-hour profile of CBT for each group showed a
      similar circadian rhythm. In simultaneously collected blood samples, each group
      showed a similar circadian profile of serum cortisol with a peak occurring at
      08:00. CONCLUSIONS: Subjects with CFS have normal CBT despite frequent self
      reports of subnormal body temperature and low-grade fever.

PMID- 9513741
TI  - Carbamazepine in the treatment of neuroleptic malignant syndrome.
AB  - BACKGROUND: Neuroleptic malignant syndrome (NMS) is a potentially lethal adverse
      effect to neuroleptic drugs. METHODS: We report on 2 cases where NMS dramatically
      improved with carbamazepine. Incidental removal and reapplication of
      carbamazepine attests to its effectiveness for this condition. RESULTS: A 34-year
      old woman treated for a major depressive disorder experienced NMS with a
      phenothiazine. Her condition dramatically improved in 8 hours after she was
      administered carbamazepine. Since carbamazepine was discontinued, NMS recurred in
      10 hours and remitted anew within less than 24 hours after reintroduction. A 31
      year-old woman experiencing a schizoaffective disorder displayed NMS with
      aphenothiazine and a butyrophenone. NMS completely resolved within 8 hours after
      she was administered carbamazepine. NMS recurred within 12 hours after
      carbamazepine discontinuation. CONCLUSIONS: These data thus account for a cause
      effect relationship between carbamazepine administration and NMS relief, and
      argue against the neuroleptic withdrawal to be responsible by itself for NMS
      relief.

PMID- 9513743
TI  - Divergent responses to fluoxetine from two compulsive, food-related conditions:
      bulimia nervosa and compulsive water drinking.
AB  - BACKGROUND: The association of compulsive water drinking with bulimia nervosa is
      rarely encountered. Nevertheless similar behavior patterns could involve a common
      pathophysiological mechanism. METHODS: A case report with the association of
      those two disorders is described. Treatment with fluoxetine was introduced to
      alleviate the compulsive aspects of those disorders. RESULTS: Fluoxetine had a
      positive effect on bulimia nervosa but none on compulsive water drinking.
      CONCLUSIONS: The different response to pharmacologic treatment could mean that
      bulimia nervosa and compulsive water drinking are based on different
      physiological mechanisms.

PMID- 9513742
TI  - Abnormal peripheral benzodiazepine receptor density associated with generalized
      social phobia.
AB  - BACKGROUND: Peripheral benzodiazepine receptors (PBRs) are involved in regulating
      stress responses. Abnormally low numbers of platelet PBRs have been found in
      patients with panic disorder, posttraumatic stress disorder, and generalized
      anxiety disorder, but not in patients with obsessive-compulsive disorder (OCD) or
      major depressive disorder (MDD). The purpose of this study was to evaluate the
      PBR density on platelets from patients with generalized social phobia (GSP).
      METHODS: The density (Bmax) and dissociation constant (Kd) of platelet PBRs was
      determined for 53 medication-free patients with GSP and an equal number of
      control subjects (NC). RESULTS: The GSP group was found to have a significantly
      lower PBR Bmax than the NC group (GSP = 2764 +/- 1242 vs. NC = 4327 +/- 1850
      fmol/mg protein, df = 1,100, F = 22.7, p = .00001). CONCLUSIONS: GSP shares this
      PBR abnormality with some other anxiety disorders but not with OCD or MDD. PBRs
      may play a role in the pathophysiology of some anxiety disorders.

PMID- 9513744
TI  - Fatty acids, cytokines, and major depression.

PMID- 9513745
TI  - Depletion of omega-3 fatty acid levels in red blood cell membranes of depressive
      patients.
AB  - BACKGROUND: It has been hypothesized that depletion of cell membrane n3
      polyunsaturated fatty acids (PUFA), particularly docosahexanoic acid (DHA), may
      be of etiological importance in depression. METHODS: We measured the fatty acid
      composition of phospholipid in cell membranes from red blood cells (RBC) of 15
      depressive patients and 15 healthy control subjects. RESULTS: Depressive patients
      showed significant depletions of total n3 PUFA and particularly DHA. Incubation
      of RBC from control subjects with hydrogen peroxide abolished all significant
      differences between patients and controls. CONCLUSIONS: These findings suggest
      that RBC membranes in depressive patients show evidence of oxidative damage.
      Possible interpretations, and implications for the etiology and treatment of
      depression, are discussed.

PMID- 9513746
TI  - Recovery from major depression is not associated with normalization of
      serotonergic function.
AB  - BACKGROUND: Plasma prolactin response to fenfluramine, a serotonergic agent, is
      typically blunted in moderately to severely depressed adults when compared to
      healthy controls. It is not clear, however, whether this dysregulation represents
      an acute change during symptomatic depression or a chronic disturbance. METHODS:
      In the current study, the prolactin responses to D,L-fenfluramine (weight
      adjusted oral dose) of 29 adults who had a history of at least one major
      depressive episode (DSM-III-R criteria), but not during the past year, were
      compared to the prolactin responses of 58 age-, sex-, and socioeconomic status
      matched adults without a lifetime history of major depression. RESULTS:
      Individuals with a positive history of major depression had significantly lower
      peak prolactin responses than controls. This finding was not attributable to
      weight, fenfluramine bioavailability, or baseline prolactin levels. CONCLUSIONS:
      This is the first investigation to compare men and women with a history of
      depression but not depressed at the time of the fenfluramine challenge to a
      similar group of healthy controls. The results are consistent with the hypothesis
      that central serotonergic activity is persistently disturbed in adults who
      experience depressive episodes.

PMID- 9513747
TI  - Platelet cytosolic calcium responses to serotonin in depressed patients and
      controls: relationship to symptomatology and medication.
AB  - BACKGROUND: Serotonin produces an exaggerated rise in platelet cytosolic calcium
      (delta [Ca++]i) in patients with mood disorders. Studies on patients with bipolar
      disorder consistently demonstrate calcium abnormalities. By comparison, data on
      patients with major depression are more variable. METHODS: To determine causes of
      variability, we utilized Fura-2 loaded platelets to compare changes in platelet
      intracellular calcium levels (delta [Ca++]i) following serotonin stimulation in
      24 patients with major depression and in 20 controls. We also sought
      relationships between the delta [Ca++]i responses and scores on clinical
      depression and anxiety scales. RESULTS: We found positive correlations between
      delta [Ca++]i responses and the clinical scales across all subjects. Furthermore,
      depressed patients with high anxiety had significantly increased delta [Ca++]i
      responses compared to depressed patients with low anxiety. In addition, patients
      receiving selective-serotonin reuptake inhibitors (SSRIs) demonstrated reduced
      delta [Ca++]i responses compared to patients not on SSRIs. CONCLUSIONS: Since
      elevations in [Ca++]i mediate platelet aggregation and secretion cascades, the
      enhanced responsivity observed in depressed, and in particular anxious, depressed
      patients may contribute to their increased risk for vascular disease.

PMID- 9513748
TI  - Effects of electroconvulsive therapy in adolescents with severe endogenous
      depression resistant to pharmacotherapy.
AB  - BACKGROUND: This open, prospective study examined the effects of
      electroconvulsive therapy (ECT) in 10 adolescents with primary, endogenous,
      psychotic depression who were resistant to antidepressant pharmacotherapy.
      METHODS: Change in symptom severity from baseline was assessed weekly with
      Hamilton Depression Rating Scale (HDRS) ratings, and outcome was measured
      additionally at 1 month, and again at 1 year, post-ECT. RESULTS: All but 1
      patient demonstrated dramatic improvement, with statistically significant
      decreases in mean HDRS score detected after the first week of treatment. All
      responders maintained the benefits of their treatment. CONCLUSIONS: The results
      provide evidence of the clinical effectiveness of ECT in adolescents with
      phenomenological characteristics shown to be predictive of ECT response in
      adults.

PMID- 9513749
TI  - The neurobiology of tryptophan depletion in depression: effects of intravenous
      tryptophan infusion.
AB  - BACKGROUND: Previous work has suggested that acute depletion of the serotonin (5
      HT) precursor tryptophan (TRP) causes transient compensatory changes in the 5-HT
      system that might be exploited for their antidepressant effects. In this study,
      neuroendocrine and mood responses to intravenous (i.v.) infusion of TRP were
      examined in order to evaluate central 5-HT function in depressed patients
      undergoing acute TRP depletion. METHODS: Thirty-eight drug-free patients with DSM
      III-R major depression participated. Each patient underwent two randomized,
      double-blind TRP depletion tests, one sham and one active. At the estimated time
      of maximum TRP depletion, each patient received an i.v. infusion of TRP 100
      mg/kg. Blood was obtained for serum cortisol, prolactin, and growth hormone. Mood
      was assessed using standardized rating scales. RESULTS: The cortisol response to
      i.v. TRP was significantly greater during TRP depletion than during sham
      depletion. Depressive symptoms showed a tendency to decrease after i.v. TRP
      following active, but not sham, TRP depletion. CONCLUSIONS: These findings are
      consistent with the present hypothesis and previous evidence that acute TRP
      depletion in drug-free depressed patients induces compensatory upregulation of
      postsynaptic 5-HT receptors. These changes are insufficient to serve as a means
      of effecting clinical improvement, but suggest that the antidepressant properties
      of rapid, marked manipulations of 5-HT function warrant further study.

PMID- 9513750
TI  - Cognitive deficits in obsessive-compulsive disorder on tests of frontal-striatal
      function.
AB  - BACKGROUND: Although neuropsychological and neuroimaging studies of obsessive
      compulsive disorder (OCD) have implicated the frontal cortex and subcortical
      structures in the pathophysiology of the disorder, few studies have examined
      cognitive function in patients with OCD on tasks validated in the assessment of
      frontal lobe and subcortical dysfunction. METHODS: The accuracy and latency of
      executive and visual memory function was assessed in 23 nondepressed OCD patients
      and 23 normal healthy controls matched for age, sex, education, and estimated IQ.
      RESULTS: The patients with OCD performed within the normal range on tasks of
      short-term memory capacity, delay dependent visual memory, pattern recognition,
      attentional shifting, and planning ability; however, specific cognitive deficits
      related to spatial working memory, spatial recognition, and motor initiation and
      execution were observed in the patient group. These deficits were not correlated
      with aspects of the patients' intellectual functioning or comorbid psychological
      symptoms, suggesting that the impairments were related to the specific clinical
      features of OCD. CONCLUSIONS: Patients with OCD showed specific cognitive
      deficits on tasks of executive and visual memory function. The pattern of
      impaired performance in these patients was qualitatively similar to the
      performance of patients with frontal lobe excisions and subcortical pathology on
      the same test battery, suggesting that the underlying pathophysiology of the
      disorder could best be conceptualized as reflecting dysfunction of frontal
      striatal systems.

PMID- 9513751
TI  - Alterations of autonomic cardiac control in anorexia nervosa.
AB  - BACKGROUND: The authors investigated autonomic cardiac function in anorexia
      nervosa. METHODS: Forty-eight patients, who in the present or past met the DSM
      III-R criteria for anorexia nervosa, and 16 normal control subjects participated
      in a standardized analysis of heart rate variability during supine and standing
      postures. RESULTS: Several heart rate variability parameters showed an inverse
      correlation to the present weight of the anorexic subjects. The values of the
      spectral power analyses were significantly (p < .01) lower in patients (n = 18)
      weighing less than 75% of ideal weight when compared to the results found in the
      control group; however, the heart rate variability parameters of anorexic
      subjects with restored weight (n = 12) did not differ from those of the control
      subjects. CONCLUSIONS: The obtained results provide evidence for autonomic
      cardiac dysfunction in acutely ill anorexic patients. Further research is
      required to elucidate possible clinical consequences of these findings.

PMID- 9513752
TI  - Bipolar disorder in adult patients with Tourette's syndrome: a clinical study.
AB  - BACKGROUND: Although recent clinical and epidemiological studies indicate that
      Tourette's syndrome (TS) is associated with a higher than expected rate of
      bipolar disorder (BPD), the clinical characteristics of BPD in patients with TS
      have not been widely investigated. METHODS: Thirty adult TS patients with
      comorbid BPD were selected from a consecutive series of 90 referred TS patients
      and examined using structured psychiatric rating scales. RESULTS: The full
      clinical spectrum of BPD was found, including bipolar I disorder, schizoaffective
      bipolar disorder, bipolar II disorder, and cyclothymic disorder. Atypical
      vegetative depressive symptoms, rapid cycling patterns, and seasonal patterns of
      recurrence were also documented. In the present clinical sample, BPD mainly
      occurred in patients with mild tic symptoms and was invariably associated with a
      high lifetime prevalence of general psychopathology, including generalized
      anxiety disorder, obsessive-compulsive disorder, panic, phobias, eating
      disorders, self-injurious behavior, attention-deficit hyperactivity disorder,
      impulse control disorders, and personality disorders. CONCLUSIONS: The results of
      this clinical study indicate that BPD and nonaffective psychopathology may be
      prominent comorbid disorders in a subpopulation of patients with TS.

PMID- 9513753
TI  - Atrial natriuretic hormone decreases endocrine response to a combined
      dexamethasone-corticotropin-releasing hormone test.
AB  - BACKGROUND: An escape from the dexamethasone-induced suppression of pituitary
      adrenocortical activity can be provoked by corticotropin-releasing hormone (CRH)
      in depressed patients, but not in healthy controls. One important antagonist of
      the CRH-stimulated secretion of corticotropin (ACTH) and cortisol is atrial
      natriuretic hormone (ANH). METHODS: To study a potential role of ANH in the
      dexamethasone-CRH test, we investigated 7 healthy men who did not suppress
      cortisol below 40 ng/mL after they had received 0.5 mg dexamethasone the evening
      before. RESULTS: We found 1) that the CRH-stimulated ACTH and cortisol secretion
      was significantly reduced by the administration of ANH in comparison to saline;
      and 2) that there was an increased pituitary-adrenocortical ratio. CONCLUSIONS:
      Our results support the view that ANH may also be involved in the frequently
      observed nonsuppression after dexamethasone during depression. Biol Psychiatry.

PMID- 9513754
TI  - Differential resting quantitative electroencephalographic alpha patterns in women
      with environmental chemical intolerance, depressives, and normals.
AB  - BACKGROUND: Previous research suggests that a subset of individuals with
      intolerance to low levels of environmental chemicals have increased levels of
      premorbid and/or comorbid psychiatric disorders such as depression, anxiety, and
      somatization. The purpose of this study was to evaluate the psychological
      profiles and quantitative electroencephalographic (qEEG) profiles at baseline of
      women with and without chemical intolerance (CI). METHODS: Participants were
      middle-aged women who reported illness from the odor of common chemicals (CI, n =
      14), depressives without such intolerances (D, n = 10), and normal controls (N, n
      = 11). They completed a set of psychological scales and underwent two separate
      qEEG recording laboratory sessions spaced 1 week apart, at the same time of day
      for each subject. RESULTS: CI were similar to D with increased lifetime histories
      of physician-diagnosed depression (71% vs. 100%), Symptom Checklist 90 (revised)
      (SCL-90-R) somatization scores, Barsky Somatic Symptom Amplification, and
      perceived life stressfulness, although D had more distress than either CI or N on
      several other SCL-90-R subscales. CI scored significantly higher on the McLean
      Limbic Symptom Checklist somatic symptom subscale than did either D or N. On
      qEEG, CI exhibited significantly greater overall resting absolute alpha activity
      with eyes closed, especially at the parietal midline site (Pz), and increased
      (sensitized) frontal alpha from session 1 to 2, in contrast with the D and N
      groups. D showed right frontal asymmetry in both sessions, in comparison with CI.
      CONCLUSIONS: The data indicate that CI with affective distress diverge from both
      D without chemical intolerance and N in qEEG alpha patterns at resting baseline.
      Although CI descriptively resemble D with increased psychological distress, the
      CI's greater alpha suggests the possibility of a) central nervous system hypo-,
      not hyper-, activation; and/or b) an overlap with EEG alpha patterns of persons
      with positive family histories of alcoholism.

PMID- 9513755
TI  - Antidepressantlike effects of chronic nicotine on learned helplessness paradigm
      in rats.
AB  - BACKGROUND: The association between smoking and depression has been widely
      investigated. Smoking cessation is known to induce depression to a variable
      extent, and patients with a history of depression are more likely to experience
      depressive symptoms. To investigate the hypothesis that nicotine may have an
      antidepressantlike effect, we used learned helpless rats as an animal model of
      depression. METHODS: Learned helplessness was produced according to our previous
      method. Learned helpless rats were implanted with nicotine and escape test was
      performed at 7 and 14 days after the implantation. RESULTS: The number of escape
      failure in the rats receiving 1.5 mg/kg/day of nicotine was significantly reduced
      (p < .05) compared to control at day 14. Furthermore, this effect was blocked
      when the nicotinic receptor antagonist mecamylamine was coadministered.
      CONCLUSIONS: These results suggest that chronic nicotine may act as an
      antidepressant, probably via nicotinic receptors.

PMID- 9513757
TI  - Advances in peritoneal dialysis: towards improved efficacy and safety.
AB  - BACKGROUND: The success of peritoneal dialysis on the short-term is mainly
      dependent on the prevention of infectious and technical complications. The mid
      term results will to a large extent be determined by the ability to remove enough
      uraemic toxins to prevent uraemic complications and malnutrition. The long-term
      challenge is the prevention of the development of structural abnormalities of the
      peritoneum leading to ultrafiltration failure and sometimes peritoneal sclerosis.
      METHODS: A review of the literature on the possibilities to increase the removal
      of uraemic waste products from the body, and on strategies to detect and prevent
      deteriorations of the peritoneal membrane during long-term dialysis treatment.
      RESULTS AND CONCLUSIONS: Improved efficacy and safety of peritoneal dialysis on
      the midterm can be achieved by individualization of the dialysis prescription
      taking residual renal function especially into account. Early start of dialysis
      might reduce the progression rate of renal function deterioration, but exposes
      the peritoneum to bio-incompatible dialysis solutions for a longer time. The long
      term alterations in the peritoneal membrane are probably mainly caused by the
      continuous exposure to dialysis fluids, especially glucose, and perhaps the
      combination of low pH with lactate. The implications of long-term continuous
      ambulatory peritoneal dialysis using only more biocompatible dialysis fluids are
      not clear. To improve the efficacy and safety of peritoneal dialysis, careful
      monitoring of patients and dialysis is mandatory. This should include 24-hour
      urine collections and 24-hour dialysate collections to calculate the residual
      glomerular filtration rate and adequacy parameters. A peritoneal membrane
      function test should be done regularly with 3.86% glucose dialysate, including
      determinations of dialysate Na+ and cancer antigen 125 to detect patients who are
      at risk for the development of structural abnormalities of the peritoneum.

PMID- 9513756
TI  - Relationships between thyroid hormone and antidepressant responses to total sleep
      deprivation in mood disorder patients.
AB  - BACKGROUND: Acute transient antidepressant effects of sleep deprivation are
      consistently observed in 50% of depressed patients, but the mechanisms of these,
      at times, dramatic improvements in mood have not been adequately elucidated.
      Some, but not all, studies suggest a relationship to increased thyroid
      stimulating hormone (TSH) secretion. METHODS: TSH and other thyroid indices were
      measured at 8:00 AM after a baseline night's sleep and at 8:00 AM following a
      night of total sleep deprivation (S.D.) in 34 medication-free, affective disorder
      patients assessed with Hamilton, Beck, and Bunney-Hamburg depression ratings as
      well as two hourly self-ratings on a visual analog scale. RESULTS: Compared with
      baseline, S.D. induced highly significant increases in TSH, levothyroxine, free
      levothyroxine, and triiodothyronine. The 12 S.D. responders tended to have
      greater TSH increases than the 15 nonresponders (p < .10). The change in Beck
      depression ratings significantly correlated with the change in TSH (r = -.40, p =
      .0496, n = 24). CONCLUSIONS: These data are consistent with several other reports
      of a significant relationship between degree of antidepressant response to S.D.
      and increases in TSH measured at 8:00 AM near their usual nadir. Acute removal of
      the sleep-related break on the hypothalamic-pituitary-thyroid axis remains a
      promising candidate for the mechanism of sleep deprivation-induced improvement in
      mood in depressed patients.

PMID- 9513758
TI  - Changes of hemorheological and biochemical parameters after plasma perfusion
      using a tryptophan-polyvinyl alcohol adsorber leading to clinical improvement in
      patients suffering from maculopathy.
AB  - BACKGROUND: Selective adsorption is an extracorporeal treatment able to reduce
      high-molecular-weight proteins and lipids. We evaluated its efficacy in lowering
      hemorheological parameters to achieve a better microcirculation of the retina.
      PATIENTS AND METHODS: Ten patients suffering from maculopathies of various origin
      underwent a selective plasma adsorption procedure using the TR-350. Plasma and
      whole blood viscosity, erythrocyte aggregation and proteins and lipids were
      determined before and 24 h after therapy. RESULTS: Selective adsorption therapy
      reduced the high-molecular-weight proteins and lipids. Plasma viscosity,
      standardized whole blood viscosity and erythrocyte aggregation were significantly
      lowered to 87, 88 and 65%, respectively, of their values prior to treatment. An
      improvement of visual acuity was achieved in 6/10 patients. Minor side effects
      were noted in 2/10 patients. CONCLUSIONS: Selective adsorption using the TR-350
      adsorber is a safe technique, showing a high impact on blood rheology. The
      changes of hemorheological parameters led to clinical improvement in 6/10
      patients suffering from retinal disorders.

PMID- 9513759
TI  - Effects of treatment of secondary hyperparathyroidism on the lipid profile in
      patients on hemodialysis.
AB  - Abnormalities in circulating lipoprotein concentrations are a characteristic
      finding in patients undergoing dialytic therapy. A substantial number of these
      patients display type IV hyperlipoproteinemia. Certain data suggest that
      secondary hyperparathyroidism may induce disturbances in lipid metabolism. To
      evaluate the effects of pulse calcitriol therapy on the lipid profile in these
      patients, we undertook a prospective study in 12 patients on stable bicarbonate
      hemodialysis. Lipid parameters comprising cholesterol and the low- as well as the
      high-density lipoprotein subfractions, triglycerides, apolipoproteins A and B,
      serum parathyroid hormones (iPTH), alkaline phosphatase, calcium, phosphorus,
      hematocrit, and blood urea were obtained prior to commencement of pulse
      calcitriol therapy and again 8-10 weeks later. Calcitriol therapy was associated
      with a decrease in serum iPTH levels (701 +/- 103.9 vs. 220.3 +/- 50.5 pmol/l; p
      < 0.001). Significant increases in high-density lipoprotein cholesterol (32.8 +/-
      2.7 vs. 38.8 +/- 2.3 mmol/l; p < 0.05) and apolipoprotein A-I (107.8 +/- 6.1 vs.
      121.8 +/- 5.8 g/l; p < 0.05) were noted during the course of the study. Moreover,
      serum iPTH correlated inversely with high-density lipoprotein cholesterol and
      apolipoprotein A-I. There were no changes in other lipid parameters except for
      low-density lipoprotein cholesterol which showed a tendency to increase. We
      conclude that in short-term study, pulse oral calcitriol therapy is associated
      with an improvement in the lipid profile in patients with secondary
      hyperparathyroidism. However, it remains to be established whether ameliorating
      the uremic dyslipidemia results in any long-term clinical benefits.

PMID- 9513760
TI  - Intradialytic cytokine gene expression.
AB  - Along with the numerous technological improvements in molecular biology,
      polymerase chain reaction, which permits analysis of sequences of a very small
      amount of biological material, enables evaluation of hemodialysis-induced gene
      transcription of inflammatory cytokines. Blood samples drawn from 22 hemodialysis
      patients, treated with cellulose-derived or synthetic membranes, were collected
      at 0 and 15 min of hemodialysis. Total RNA, purified from mononuclear cells, was
      reverse transcribed and cDNA amplified by polymerase chain reaction primed with
      specific oligomers in order to determine tumor necrosis factor alpha (TNF alpha),
      interleukin (IL) 1 beta and IL6 gene expression. Plasma samples were collected at
      0 and 180 min for detection of mature cytokines by enzyme immunoassay with plates
      pre-coated with monoclonal antibodies to TNF alpha, IL1 beta and IL6. A
      significant increase in TNF alpha mRNA was detected at 15 min of hemodialysis in
      12 of 22 patients: 5 of 9 treated with cuprophan; 3 of 3 with cellulose
      triacetate; 3 of 5 with polysulfone, and only 1 of 5 treated with polymethyl
      methacrylate membranes. A parallel increase in IL1 beta or IL6 mRNA was detected,
      and significant relationships were found between TNF alpha and IL1 beta (p <
      0.001), and IL1 beta and IL6 gene expression (p < 0.05). Increased levels of
      mature TNF alpha and IL1 beta molecules in plasma were detected in the majority
      of patients showing an increased cytokine gene expression. However, the absolute
      amount of cytokine mRNA transcription at 15 min did not predict the levels of
      mature molecules reached in plasma at 180 min. Cytokine mRNA transcription is
      quite common at the beginning of a dialysis run. Possibly due to intracellular
      degradation of critical sequences of cytokine mRNA, gene expression does not
      necessarily imply translation into mature protein. It is suggested that
      mechanisms related to cell-to-cell interaction, which may possibly involve
      procytokine biology, are needed to drive phenomena of cytokine activation to
      clinical effectiveness.

PMID- 9513761
TI  - Effects of cascade apheresis in patients with psoriasis and psoriatic
      arthropathy.
AB  - Eight patients with psoriasis, all with skin scales and 7 with disabling
      psoriatic arthritis, were subjected to cascade apheresis starting with three
      treatments per week for 2 weeks, followed by one treatment a week, comprising ten
      treatments in all. Six out of 7 patients (86%) with arthropathy and 3 out of 8
      patients (38%) with scales experienced a beneficial effect. There was a large
      drop in the levels of circulating immune complexes (CIC) due to the treatment,
      and the removal of CIC was followed by reduced inflammatory activity in skin
      lesions and joints as evaluated by pain, morning stiffness, grip strength, plaque
      score, and PASI index. However, there was no correlation between the level of
      CIC, disease activity, or treatment response. From the present results it is
      concluded that CIC may play a more significant role regarding psoriatic
      arthropathy than in skin manifestations, and apheresis may be beneficial in
      patients not responding to conventional therapy.

PMID- 9513762
TI  - Successful treatment of tumoral calcinosis using CAPD combined with hemodialysis
      with low-calcium dialysate.
AB  - Successful treatment of tumoral calcinosis using continuous ambulatory peritoneal
      dialysis (CAPD) combined with hemodialysis is described. A 32-year-old male
      patient with a 2-year history of CAPD rapidly developed multiple metastatic
      calcification (tumoral calcinosis) adjacent to his fingers, elbows, and knee
      joints. Tests showed severe hyperphosphatemia, moderate hypercalcemia, and
      increased Ca-P product without elevation of intact parathyroid hormone. An
      enlarged parathyroid gland was not found by echography. In order to rapidly lower
      the excessive Ca and P levels, a combined therapy with CAPD and vigorous
      transient hemodialysis using a low-Ca dialysate was performed. In parallel, the
      patient was given calcitonin, bisphosphonate, and short-term Al to ameliorate the
      metastatic calcifications more effectively. The result was dramatic with
      disappearance of the tumoral calcinosis as well as improvement in subjective
      symptoms within a few months. The present case suggests that combined therapy
      with hemodialysis and CAPD using a low-Ca dialysate, together with Ca-modulating
      agents, can be effective in ameliorating tumoral calcinosis in patients on CAPD.

PMID- 9513763
TI  - Elimination of drugs by the new polyamide hemofilter FH77H during various in
      vitro conditions.
AB  - BACKGROUND/AIMS: Multiple organ failure alters the dosage of drugs during
      hemofiltration. To separate factors, we utilized in vitro hemofiltration to
      investigate different blood flows, protein concentrations and intracellular drug
      partition with the FH77H polyamide membrane. METHODS: One liter of warm
      heparinized fresh human blood was hemofiltrated in two series: (1) with digoxin,
      netilmycin, phenobarbital, ceftriaxone and teicoplanin, and (2) with amikacin,
      theophylline, ceftazidim, phenytoin and vancomycin and, in addition, with cell
      free fresh frozen plasma. RESULTS: The increased volumes of distribution of
      aminoglycosides and theophylline were a combined result of partition into cells
      and adsorption into the filter membrane. The deviations of drug sieving from
      predicted values were due to different affinities of the drugs on whole blood
      binding sites. CONCLUSION: The in vitro composition of drugs and blood improved
      the detection of factors that influence drug elimination during hemofiltration.
      The FH77H polyamide hemofilter facilitates more precise predictions of drug
      dosages by low adsorption rates to the membrane.

PMID- 9513764
TI  - Eye don't know.

PMID- 9513765
TI  - Ophthalmology undergraduate education in Canada.
AB  - OBJECTIVE: To compile a database recording components of undergraduate education
      in ophthalmology in Canada. DESIGN: Mailed questionnaire survey. SETTING: The 16
      Canadian medical schools. PARTICIPANTS: All ophthalmology undergraduate program
      directors. OUTCOME MEASURES: Teaching hours, subjects and clinical skills taught,
      examination methods. RESULTS: Almost all schools covered a similar curriculum and
      used multiple-choice examinations. The number of hours devoted to preclerkship
      teaching was similar, but only seven schools had a mandatory clerkship rotation.
      Overall, 69% of the annual graduating medical school class receive clinical
      exposure to ophthalmology during their clerkship. Almost all schools provided
      electives that were similar in structure. CONCLUSIONS: There was great similarity
      in the curricula for medical student teaching in Canada. Efforts should be
      undertaken to increase the proportion of medical students receiving clinical
      teaching in ophthalmology. Increased coordination and collaboration in
      undergraduate teaching can be achieved in specific areas with future data
      sharing.

PMID- 9513766
TI  - Endophthalmitis cluster from contaminated donor corneas following penetrating
      keratoplasty.
AB  - OBJECTIVE: To attempt to identify common events or factors in four cases of
      endophthalmitis that developed after penetrating keratoplasty performed within a
      1-week interval. DESIGN: Case series. SETTING: Tertiary care eye hospital in
      Riyadh, Saudi Arabia. PATIENTS: Four patients in whom endophthalmitis developed
      after penetrating keratoplasty performed in May 1993. OUTCOME MEASURES: Source of
      donor tissue, transportation of corneas, handling of corneas at the eye hospital,
      and causative organism and sensitivity profile. RESULTS: The donor tissue in all
      four cases originated from the same eye bank. Organisms were cultured from 10 of
      the 11 donor rims from eye bank A tissue used during the week in question. The
      causative organisms were Enterococcus faecalis in three patients and Torulopsis
      glabrata in one patient. In each case the same organism was cultured from the
      recipient eye and the corresponding donor rim. Two of the four patients had a
      favourable outcome. CONCLUSIONS: Donor rim culture is essential if the cause of
      endophthalmitis after penetrating keratoplasty is to be determined. Close
      communication between eye bank personnel, the microbiology laboratory and the
      operating surgeon is important as it may influence early detection, choice of
      treatment and outcome of endophthalmitis after penetrating keratoplasty.
      Epidemiologic studies from both the source eye bank and the recipient facility
      are required to fully investigate the cause of a cluster of endophthalmitis cases
      from contaminated donor tissue following penetrating keratoplasty.

PMID- 9513767
TI  - Epiphora in patients receiving systemic 5-fluorouracil therapy.
AB  - OBJECTIVE: To determine the prevalence of tearing and canalicular fibrosis in
      patients receiving systemic 5-fluorouracil (5-FU) therapy and the reversibility
      of the symptoms when treatment is stopped. DESIGN: Prospective study. SETTING:
      University-affiliated tertiary care hospital in Toronto. PATIENTS: Thirty
      patients (17 men and 13 women aged 38 to 81 years) with advanced gastrointestinal
      carcinoma receiving intravenous 5-FU therapy as palliative (weekly) treatment (20
      patients) or adjunctive (cycle) treatment (10 patients). OUTCOME MEASURES:
      Tearing, eyelid changes and canalicular fibrosis during and after treatment.
      Patients who experienced tearing were advised to massage and wipe the lower
      eyelids in an upward direction. RESULTS: Tearing and canalicular fibrosis
      developed in 10 patients (50%) and 3 patients (15%) respectively in the
      palliative treatment group; no patient in the adjunctive treatment group
      experienced these side effects. In the palliative treatment group, the patients
      who experienced tearing received double the dose of 5-FU (p = 0.03) and received
      treatment for twice as long (p = 0.042) as those who did not experience tearing.
      Of the patients with tearing, those in whom canalicular fibrosis developed
      received treatment for three times as long as those without fibrosis and received
      2.6 times the total dose (p < 0.000). Of the seven patients with tearing in whom
      canalicular fibrosis did not develop, four stopped 5-FU treatment, and 2 to 4
      weeks later the epiphora disappeared. CONCLUSIONS: Our findings suggest that the
      prevalence of tearing and canalicular fibrosis in patients receiving systemic 5
      FU therapy as palliative treatment is related to the total dose and duration of
      treatment. Such side effects are less likely in those receiving adjunctive
      therapy. The epiphora is often reversible on stopping therapy if canalicular
      fibrosis has not yet developed.

PMID- 9513768
TI  - Conservative photorefractive keratectomy for residual myopia following radial
      keratotomy.
AB  - OBJECTIVE: To evaluate the efficacy, predictability, stability and safety of a
      conservative approach to photorefractive keratectomy (PRK) (treating only 60% to
      70% of the residual myopia) for residual myopia following radial keratotomy (RK).
      DESIGN: Case series. SETTING: Laser eye surgery centre in Windsor, Ont. PATIENTS:
      Thirty-three eyes of 27 patients with an average age of 40.1 years who underwent
      PRK between January 1993 and July 1995, 12 months or more after RK. All were
      followed for at least 12 months after PRK. OUTCOME MEASURES: Efficacy and safety
      were assessed by changes in the uncorrected and best corrected visual acuity.
      Predictability was determined by the proximity of the final result to emmetropia.
      The stability of the refractive outcome was assessed over the follow-up period.
      RESULTS: At 12 months 12 eyes (36%) had 20/20 or better uncorrected visual acuity
      and 29 eyes (88%) had 20/40 or better uncorrected acuity. Twenty-seven eyes (82%)
      were within 0.50 D of emmetropia, and 30 eyes (91%) were within 1.00 D of
      emmetropia. There was a significant change in the mean postoperative spherical
      equivalent between 1 and 3 months (p < 0.001); however, there was no significant
      change after this time. Six eyes (18%) had a loss of 2 or more lines of best
      corrected visual acuity due to corneal haze; however, retreatment reduced this
      incidence to 9% at 12 months. CONCLUSIONS: Our results show that conservative PRK
      for residual myopia following RK is efficacious and predictable and produces
      stable results. However, the risk of postoperative haze reduces the safety of
      this procedure.

PMID- 9513769
TI  - The use of tissue plasminogen activator in silicone oil-filled eyes.

PMID- 9513770
TI  - Severe congenital ectropion secondary to lamellar ichthyosis.

PMID- 9513771
TI  - Endoresection of a ciliary body leiomyoma.

PMID- 9513772
TI  - Bilateral serous retinal detachments associated with Goodpasture's syndrome.

PMID- 9513773
TI  - Advances in radiation therapy. Introduction.

PMID- 9513774
TI  - Three-dimensional treatment planning and conformal dose delivery--a physicist's
      perspective.

PMID- 9513775
TI  - Radiation therapy beam modulation techniques.

PMID- 9513776
TI  - Computer-controlled delivery of 3D conformal radiation treatments.

PMID- 9513777
TI  - Implementation and clinical use of portal imaging.

PMID- 9513778
TI  - Altered fractionation: radiobiological principles, clinical results, and
      potential for dose escalation.

PMID- 9513779
TI  - Pharmacologic modification of radiation-induced late normal tissue injury.

PMID- 9513780
TI  - Role of gene therapy in radiation oncology.

PMID- 9513781
TI  - Potential applications of cell cycle manipulation to clinical response.

PMID- 9513782
TI  - Advances in brachytherapy.

PMID- 9513784
TI  - Implementation of newer radiotherapeutic technology in the management of prostate
      cancer.

PMID- 9513783
TI  - Recent advances in external electromagnetic hyperthermia.

PMID- 9513785
TI  - Conformal radiation therapy--a physician's perspective.

PMID- 9513786
TI  - Clinical applications of stereotactic radiosurgery.

PMID- 9513787
TI  - Too little, too late.

PMID- 9513788
TI  - Drug uptake from the airways and lungs.
AB  - This paper reviews the mechanisms and physiological processes that act when drugs
      or chemicals are administered into the lower airways and lungs. Administration is
      usually by aerosol. Agents can be given, for example, either to treat pulmonary
      diseases such as asthma, or the test for airways' responsiveness or other
      functions, or as a means of access of a drug to the systemic circulation. The
      first barrier to absorption is the airway surface liquid, including mucus. The
      thickness of this layer will determine the concentration of the drug in solution,
      and therefore its rate of entry into the tissue. The agent must then penetrate
      the airway epithelium, the strongest barrier for hydrophilic agents. Agents must
      then diffuse through the epithelial basement membrane and the interstitium.
      Finally, the agent may be taken up into the mucosal vasculature, and changes in
      blood flow will influence its uptake and distribution. If the drug is to reach a
      target organ, such as airway smooth muscle or glands, these barriers have first
      to be traversed.

PMID- 9513789
TI  - Effects of trypan blue on the action of adrenergic agonists in the guinea-pig
      isolated atrium.
AB  - It has been reported that trypan blue, a diazo dye with polyamphipathic
      structure, can inhibit the coupling of receptors to G-proteins. The present study
      was carried out to investigate the effect of trypan blue on the actions of
      adrenoceptor agonists in the guinea-pig atrium. Trypan blue (10 and 100 microM)
      antagonized the positive inotropic effects of isoprenaline and dobutamine by
      shifting their concentration-response curves to the right. With the selective
      beta 2-adrenoceptor agonist, salbutamol, there was a reduction of response in the
      presence of trypan blue. Therefore, we concluded that trypan blue diminish the
      response to beta-adrenoceptor agonists possibly via decoupling receptors from Gs.
      Trypan blue and similar agents, due to their unique mode of action, can be used
      as tools for the investigation of the mechanism of receptor-G protein coupling in
      the whole tissue preparation.

PMID- 9513790
TI  - The effect of central and peripheral administration of acetylcholine and
      epinephrine on respiration.
AB  - The experiments were conducted in dogs anesthetized with Na-pentobarbital i.v.
      tidal volume (VT) and respiratory frequency (f min-1) were recorded. The central
      effects of acetylcholine (Ach) and epinephrine on respiration were investigated
      after injections of these substances directly into the cerebrospinal fluid by
      atlanto-occipital punction. The peripheral effects of Ach and epinephrine on
      respiration were studied after i.v. injections. Both central and peripheral
      administration of epinephrine caused significant increase in f min-1 and VT.
      After vagotomy the effects of centrally and peripherally administered epinephrine
      on f min-1 were abolished. The effect of central injection of epinephrine on VT
      persisted after vagotomy. The increase in VT in response to peripheral
      epinephrine administration was abolished by vagotomy. Both central and peripheral
      injection of Ach increased f min-1. In VT an initial decrease was followed by an
      increase. The initial decrease in VT was abolished by atropine. After vagotomy
      the effects of central and peripheral administration of Ach on f min-1 were
      abolished. The effects of central injection of Ach on VT persisted after
      vagotomy. Vagotomy abolished the effects of peripheral administration of Ach on
      VT.

PMID- 9513791
TI  - Physiological, biochemical and histological changes due to physostigmine in
      monkeys.
AB  - Physostigmine (Phy), a short-acting reversible anticholinesterase agent is
      considered to be a potent prophylactic antidote for the highly toxic
      organophosphorous (OP) compounds. The toxic effects, if any, of the probable
      prophylactic doses of Phy have been evaluated by studying its physiological,
      biochemical and histological effects in monkeys. Phy only at 100 micrograms/kg
      resulted in certain cholinergic signs such as salivation, lacrymation and
      muscular faciculations; physiological changes such as mild tachycardia,
      tachypnea, higher amplitude in electrical activity of the brain, clinico-chemical
      effects like fall in PO2, PCO2 and alkalosis and histologically an inflammatory
      reaction in the lungs. On the other hand, the lower dose, i.e. 50 micrograms/kg
      appeared to be devoid of cholinergic signs and symptoms. However, we observed a
      significant inhibition of both plasma and erythrocyte ChE and increase in the
      rectal temperature in both the Phy treated groups. From this study, Phy at a dose
      of 50 micrograms/kg could be inferred as a safe, sign free intramuscular dose and
      may probably be used in pretreatment regimen against nerve agents.

PMID- 9513792
TI  - Synergistic effect of flunarizine and sodium valproate on seizure thresholds
      elicited by cortical stimulation in conscious rats.
AB  - The effect of flunarizine (FLU) and sodium valproate (SV) alone and in
      combination were examined for their effects on seizure thresholds elicited by
      cortical stimulation in conscious rats. Two different pharmacodynamic parameters
      could be distinguished viz, the threshold for localised seizures (TLS) defined as
      the current (mu A) required to elicit forelimb clonus and the threshold for
      generalised seizure (TGS), defined as the current (mu A) required to elicit
      vigorous clonic activity without a tonic component. In preliminary neuro
      behavioral studies on rats, the most favourable combination was FLU 10 mg/kg i.p.
      and SV 200 mg/kg i.p., which produced anticonvulsant efficacy with minimal
      neurotoxicity. With FLU alone, SV alone and the combination of FLU and SV, the
      mean % change +/- SEM from baseline values over a period of 6 h were for TLS: 3.8
      +/- 0.8, 23.9 +/- 3.7, and 29.8 +/- 2.1; and for TGS 5.5 +/- 0.7, 15.6 +/- 2.7
      and 190.9 +/- 22.7 respectively, indicating that FLU alone had no effect on TLS
      or TGS, SV significantly elevated TLS but had no effect on TGS and the
      combination of FLU plus SV produced a synergistic elevation of both TLS and TGS
      the intensity of effect being more on TGS than on TLS. This model provides a new
      dimension to the profiling of two anticonvulsant agents with different mechanisms
      of anticonvulsant activity and offers predictive criteria for protective effects
      on clinical manifestations of partial or generalised tonic clonic seizure.

PMID- 9513793
TI  - Effect of N-acetylcysteine on myocardial infarct size following ischemia and
      reperfusion in dogs.
AB  - The present study was designed to examine the role of N-acetylcysteine (NAC) on
      free radical mediated reperfusion injury in canine model. Fourteen dogs underwent
      90 min of left anterior descending coronary artery (LAD) occlusion followed by 4
      h of reperfusion. Treated animals received loading dose of NAC (250 mg/kg) at the
      time of reperfusion upto 1 h followed by maintenance dose (70 mg/kg) for
      remaining 3 h through left atrial line. Infarct size, myocardial tissue lipid
      peroxidation, superoxide dismutase (SOD) and glutathione (GSH) levels were
      measured at the end of reperfusion in treated (n = 7) and untreated animals (n =
      7). Left ventricular end diastolic pressure was significantly lower in treated
      animals compared to untreated group. SOD and GSH levels in myocardial tissue at
      risk and in infarcted zone were similar in both groups. However, in NAC treated
      animals the lipid peroxidation was significantly lower in comparison to untreated
      control animals. Infarct size in the area at risk, percent left ventricular
      necrosis and myocardial tissue preservation were not significantly different in
      treated and untreated animals. These results suggests that N-acetylcysteine
      infusion at the time of reperfusion following 90 min of ischemia and 4 h of
      reperfusion fails to offer significant cardioprotection against free radical
      damage but it can improve ventricular performance by decreasing pre load.

PMID- 9513794
TI  - Autonomic changes while mentally repeating two syllables--one meaningful and the
      other neutral.
AB  - Autonomic and respiratory variables were recorded in 12 volunteers in three types
      of sessions (1). Before, during and after a test period of mentally repeating a
      meaningful syllable 'OM' (MOM session) (2). A similar session except that the
      test period was spent mentally repeating a neutral work, 'one' (COM session) (3).
      A session with non-targeted thinking (NT session). The subjects were familiar
      with both syllables, and had been meditating on 'OM' for 20 days. During the test
      periods of both MOM and COM sessions the rate of respiration (RR) and heart rate
      (HR) decreased significantly [(two factor ANOVA (RR), paired t test (RR. HR)].
      Compared to the pre period. Mental repetition of 'OM' (but not 'one') caused a
      significant decrease in skin resistance level (SRL) (paired t test). This was
      taken to mean that the subject recognized the significance of the syllable. No
      significant change occurred during NT sessions.

PMID- 9513795
TI  - Effect of training on lipid peroxidation, thiol status and antioxidant enzymes in
      tissues of rats.
AB  - The effect of training on lipid peroxidation, thiol-status and certain
      antioxidant enzymes of glutathione system was studied in blood and tissues such
      as liver and skeletal muscle of rats. Exercise training was given by subjecting
      the rats to treadmill running. Training for a period of 6 weeks resulted in
      increased lipid peroxidation (P < 0.001) as indicated by thiobarbituric acid test
      and conjugated diene measurement in liver and muscle. Thiol levels (total and non
      protein) were reduced. However, glutathione level in blood was increased and
      blood lipid peroxides were unaltered as a result of training compared to
      sedentary controls. Adaptive increases in three antioxidant enzyme activities
      were observed. The study indicates that training induces adaptation in the
      glutathione system.

PMID- 9513796
TI  - Development of neurogenic pulmonary edema at different grades of intracranial
      pressure in cats.
AB  - Development of neurogenic pulmonary edema (NPE) subsequent to increased
      intracranial pressure (ICP) was evaluated in an experimental model in cats.
      Experiments were conducted in chloralose anaesthetised animals, either on
      spontaneous respiration or on intermittent positive pressure ventilation.
      Hemodynamic parameters i.e., mean arterial pressure (MAP) and heart rate (HR)
      were continuously monitored. Pulmonary artery/right ventricular systolic pressure
      was recorded in cats on spontaneous respiration. Increase in ICP for 180 minutes
      caused an increase in extravascular lung water (EVLW) content in both
      spontaneously breathing and artificially ventilated animals. In spontaneously
      breathing animals EVLW to blood free dry weight ratio (EVLW/BFDW) was 3.95 +/-
      0.16 and 4.96 +/- 0.16 at ICP 40 and 80 mm Hg respectively while in animals on
      artificial ventilation, at 40, 60, 80 and 100 mm Hg ICP, it was 3.88 +/- 0.11,
      4.09 +/- 0.10, 4.50 +/- 0.13 and 5.03 +/- 0.17 respectively. These values were
      significantly greater (P < 0.05) as compared to that in sham operated animals
      (3.43 +/- 0.10). This was accompanied by rise in MAP, HR and pulmonary artery
      pressure. The study establishes the graded development of NPE, the severity of
      which is proportional to the levels of ICP.

PMID- 9513797
TI  - Glycaemic and insulinaemic responses to natural foods, frozen foods and their
      laboratory equivalents.
AB  - Glycaemic response to a food is determined by a large number of factors, of which
      composition is only one. The present study was designed to study the effect of
      composition and overnight refrigeration on the glycaemic response. The study
      involved determination of the glycaemic and insulinaemic response of healthy
      human volunteers to rice or potato, and to meals equivalent to these foods in
      terms of carbohydrate, protein, fat and fibre content; but made up of cornflour,
      casein, corn oil and cellulose. Further, each of these meals was served either
      freshly cooked, or after overnight storage in a refrigerator and rewarming. The
      natural foods led to a higher postprandial glycaemia than their respective
      equivalents, and the freshly cooked foods led to a higher glycaemic response than
      the refrigerated and rewarmed forms of the corresponding foods. No such
      consistent differences were observed in case of the insulinaemic responses. The
      difference in the glycaemic response to foods and their laboratory equivalents
      may be due to the unique physical arrangement of nutrients within the food or due
      to specific chemical differences in terms of macro-or micro-nutrients, non
      nutrients or anti-nutrients. The difference in the glycaemic response to freshly
      cooked and refrigerated foods may be due to the formation of resistant starch
      during cold storage.

PMID- 9513798
TI  - Glaucoma and concomitant status of autonomic nervous system.
AB  - There is much clinical evidence to suggest that certain types of Glaucoma are
      related to activity of autonomic nervous system (ANS). Although some local
      changes have been documented but systemic association has not been established,
      so far. Hence, the present study was initiated and an attempt was made to bring
      out the association of systemic autonomic functions with glaucoma (especially
      Primary Closed Angle Glaucoma (PCAG)) if any. This study was carried out in the
      Department of Physiology, Maulana Azad Medical College in association with
      Glaucoma Clinic of Guru Nanak Eye Centre, New Delhi from June 1993-August 94. ANS
      function tests were conducted using Polyrite-8-Medicare System. The subjects were
      confirmed cases of PCAG with 10P-22.1 +/- 4.4 mmHg and possibility of autonomic
      neuropathy due to any other cause was ruled out. They were matched with normal
      subjects for their age, anthropometry and were compared for their sympathetic
      activity of ANS by Galvanic Skin Resistance (GSR); Cold Pressor Response (CPR);
      corrected QT interval (QTc) and T-wave amplitude (TWA) and for parasympathetic
      activity of ANS by Resting Heart Rate (RHR); Standing to Lying Ratio (SLR) and
      Valsalva Ratio and analysed statistically using standard 't' test. The results
      obtained in this study indicated increase in sympathetic activity in 61% of PCAG
      subjects and decreased parasympathic activity in 80% of the PCAG subjects when
      compared with control group of subjects, suggesting association of autonomic
      neuropathy with PCAG.

PMID- 9513799
TI  - Abuse liability of buprenorphine--a study among experienced drug users.
AB  - Six male post-detoxified opiate dependent subjects were evaluated for abuse
      liability of buprenorphine (0.6 mg), morphine (16 mg), pentazocine (30 mg) and
      distilled water (placebo) intramuscular injection in a single blind cross-over
      random order. Subjective states, drug discrimination, drug linking, sedation and
      euphoria were assessed at pre-injection, 30 min and 4 hrs post-injection.
      Buprenorphine caused significant euphoria and was identified as heroin. On all
      parameters, buprenorphine resembled morphine rather than pentazocine and placebo.
      The data suggest that abuse liability of buprenorphine is similar to morphine
      i.e. moderate rather than low.

PMID- 9513800
TI  - Role of Lipistat in protection against isoproterenol induced myocardial necrosis
      in rats: a biochemical and histopathological study.
AB  - A test drug (Lipistat) comprising of equal-proportions of extracts of Terminalia
      arjuna, Inula racemosa Hook, latex of Commiphora mukul, in three different doses
      (225 mg/kg; 350 mg/kg; 450 mg/kg) were administered orally daily for 6 days a
      week for 60 days in rats. Thereafter, the rats were subjected to isoproterenol
      (ISO) induced (85 mg/kg, s.c. for 2 days) myocardial necrosis. Gross and
      microscopic examinations (histopathology) were done along with estimations of
      myocardial tissue high energy phosphates (HEP) stores and lactate content. Gross
      examination showed significant (P < 0.05) cardioprotection in Lipistat treated
      animals. On microscopic examination no statistically significant reduction in
      myocardial damage by 350 and 450 mg/kg of Lipistat were observed although loss of
      myocardial HEP stores and accumulation of lactate were significantly prevented.
      The results of the present study suggest the potential usefulness of Lipistat in
      the prevention of ischemic heart disease.

PMID- 9513801
TI  - Studies on the effect of intratesticular administration of opioid peptides,
      naloxone or N-acetyl beta-endorphin antiserum on some testicular parameters in
      rats.
AB  - Opioid peptides have been localized in a variety of peripheral tissues like
      placenta, thyroid, pancreas, gastrointestinal tract, in the reproductive tract of
      male and female and in the testes of rats. Immunoassayable material was detected
      in extracts of gonads, reproductive tract and accessory reproductive organs.
      Studies with naloxone have suggested that beta-endorphin may have an important
      role in steroidogenesis and may have a role in regulating transport of luminal
      material. In our studies met-enkephalin, beta-endorphin, naloxone or N-acetyl
      beta-endorphin antiserum were microinjected intra testicularly once on alternate
      days for one week and autopsied 24 h after the last injection. Intratesticular
      administration of 25, 50 and 100 micrograms doses of naloxone induced significant
      decrease in in vitro secretion of testosterone per se, which was significantly
      greater with 50 micrograms dose than with those of the other two doses. A 25
      micrograms dose had no effect on hyaluronidase or acid phosphatase activity while
      50 micrograms dose significantly decreased the enzyme activity. One hundred
      micrograms dose also significantly decreased hyaluronidase activity.
      Intratesticular injection of 10 micrograms met-enkephalin or 1 microgram beta
      endorphin significantly decreased hyaluronidase activity whereas 20 microliters N
      acetyl beta-endorphin antiserum increased the specific activity of hyaluronidase.
      There was no change in the weight of the testes on treatment with the above
      agents.

PMID- 9513802
TI  - Differing response of body weight gain to high fat diet treatment in the mouse.
AB  - Forty-eight mice maintained on a high fat diet supplement in addition to regular
      laboratory rodent chow responded differently in terms of body weight gain over a
      period of six weeks. Eleven mice gained weight that was comparable to body
      weights of mice given only chow for the same period of time while the others
      gained significantly higher body weights and became obese despite similar level
      of energy intakes. The increase in body weight was due to increase in body fat
      content as noted by carcass analysis. The differential response of the mice to
      identical dietary treatment in causing obesity or not in mice is discussed.

PMID- 9513803
TI  - Effect of the Karnatic music raga "Neelambari" on sleep architecture.
AB  - The raga Nelambari in the classical Indian Karnatic system of music is said to be
      able to induce sleep and also have some sleep promoting qualities. This
      hypothesis was scientifically tested using sleep polysomnography with eight
      healthy subjects who listened to either Neelambari (test) raga or Kalyani
      (control) raga. There was no difference in sleep architecture or in subjective
      feeling of quality of sleep. The anecdotal references to the quality of sleep
      promoting effects of Neelambari probably reflect a conditioned response since
      most lullabies in South India are sung in Neelambari raga.

PMID- 9513804
TI  - Glycoconjugate profile in plasma and erythrocytes of gastric cancer patients.
AB  - The present study has examined the glycoconjugate profile in plasma and
      erythrocyte membranes of 24 adult male gastric cancer patients and an equal
      number of age and sex-matched controls. Protein-bound hexose, hexosamine and
      sialic acid were significantly increased in plasma and erythrocytes of gastric
      cancer patients compared to controls. Elevation of glycoconjugates in circulation
      is suggested to be a result of increased shedding by the tumor cells or increased
      synthesis by liver, due to acute phase response.

PMID- 9513805
TI  - The perceptions of first-year medical students on animal and human experiments in
      physiology.
AB  - This study was conducted to ascertain the attitudes of first year medical
      students to human and animal experimentation, while undergoing a course in Muscle
      and Nerve experimental Physiology. At the time of administration of the
      questionnaire, students had been exposed to both human as well as animal
      experiments. Approximately 81% of the students preferred human experiments (P <
      0.05). This preference, however, was related more to the issue of enjoyability
      rather than the extent to which the experiment contributed to overall
      understanding and learning. 55% of students identified ethical issues related to
      laboratory experimentation. Gender and academic performance were not determinants
      of student's attitude to animal and human experimentation, although ethical
      insight was. The results suggest that while students recognize the importance and
      value of animal experiments, they would prefer the introduction of a larger
      number of human experiments.

PMID- 9513806
TI  - Effect of glucose on stress induced antinociception in normal mice.
AB  - Stress induced analgesia has been shown to utilise both non-opioidergic and
      opioidergic mechanisms. Earlier studies indicate that opiodergic analgesics
      exhibit corollary changes in blood glucose level. In this study, the changes in
      blood glucose level by swim induced stress and the influence of exogenous glucose
      administration on the stress induced antinociception were studied. Stress per se
      (both 30 sec and 3 min) did not modify the blood glucose level. However,
      exogenous administration of glucose reversed the stress induced antinociception
      in both non-opioid and opioid segments. Our results favour a role for glucose in
      stress induced analgesic activity.

PMID- 9513807
TI  - A comparative study of anxiogenic effects of fluoroquinolones in rats.
AB  - The present study compares the anxiogenic effects of three fluoroquinolones
      namely ciprofloxacin, ofloxacin and pefloxacin in rats using elevated plus-maze.
      The rats were treated with 12.5 mg/kg and 25 mg/kg of ciprofloxacin, ofloxacin or
      pefloxacin and then tested in elevated plus-maze half an hour later, for a period
      of 5 min. All the three fluoroquinolones decreased the time spent in open arm
      considerably. This decrease was statistically significant only with the higher
      doses of ciprofloxacin and ofloxacin (P < 0.05). Mean time spent in closed arm
      was increased by all the test drugs in both the doses. Increase was statistically
      significant with both the doses of ofloxacin (P < 0.05). Mean time spent in
      closed arm was increased by all the test drugs in both the doses. Increase was
      statistically significant with both the doses of ofloxacin (P < 0.05, P < 0.01
      respectively) and higher doses of ciprofloxacin and pefloxacin (P < 0.01, P <
      0.05 respectively). The number of entries in open arm and closed arm were
      decreased by both the doses of the three fluoroquinolones used in the study. The
      reduction in total number of arm entries by ciprofloxacin, ofloxacin and
      pefloxacin in both the doses was highly significant. The results suggest definite
      anxiogenic potential of fluoroquinolones.

PMID- 9513808
TI  - Body fat and lean body mass assessment in human subjects--a comparison of two
      different techniques.
AB  - Body fat and lean body mass was assessed in young college students by two
      different techniques involving NIR method and body circumference measurements.
      NIR technique significantly over-estimated the body fat as compared to the
      results obtained by the other method. The difference between the methods was 23
      30% high for fat and the variation was 5-9% low for lean body mass for the whole
      group. Results obtained by the body girth size measurements agreed well with fat
      and lean body mass values from other studies on Indian subjects which had
      employed different methods.

PMID- 9513809
TI  - Assessment of sperm count in rural population of central India.
AB  - Semen samples from 1425 males who visited the Reproductive Biology Unit, M. G. I.
      M. S., Sewagram during the period from 1984 to 1996 were analysed. The data for
      sperm count was analysed over the length of period and no change in sperm count
      was found with passage of time.

PMID- 9513810
TI  - 2',3'-cyclic neucleotide 3'-phosphodiesterase activity in developing rat brain.

PMID- 9513811
TI  - Molecular structures from low angle X-ray and neutron scattering studies.
AB  - Molecular structures can be extracted from solution scattering analyses of
      multidomain or oligomeric proteins by a new method of constrained automated
      scattering curve fits. Scattering curves are calculated using a procedure tested
      by comparisons of crystal structures with experimental X-ray and neutron data.
      The domains or subunits in the protein of interest are all represented by atomic
      coordinates in order to provide initial constraints. From this starting model,
      hundreds or thousands of different possible structures are computed, from each of
      which a scattering curve is computed. Each model is assessed for steric overlap,
      radii of gyration and R-factors in order to leave a small family of good fit
      models that corresponds to the molecular structure of interest. This method
      avoids the tedium of curve fitting by hand and error limits on the ensuing models
      can be described. For single multidomain proteins, the key constraint is the
      correct stereochemical connections between the domains in all the models.
      Successful applications to determine structures are summarised for the Fab and Fc
      fragments in immunoglobulin G, the three domain pairs in the Fc subunit of
      immunoglobulin E and the seven, domains in carcinoembryonic antigen. For
      oligomeric proteins, the key constraint is provided by symmetry and successful
      analyses were performed for the association of the monomers of the bacterial
      amide sensor protein AmiC to form trimers and pentameric serum amyloid P
      component to form decameric structures. The successful analysis of the
      heterodimeric complex of tissue factor and factor VIIa required the use of
      constraints provided from biochemical data. The outcome of these analyses is
      critically appraised, in particular the biological significance of structures
      determined by these solution scattering curve fits.

PMID- 9513812
TI  - Free radical depolymerization of hyaluronan by Maillard reaction products: role
      in liquefaction of aging vitreous.
AB  - The degradation of hyaluronan was followed by viscosimetry and by HPLC in order
      to study the possible role of Maillard products (lysine-glucose) on the
      alteration of the vitreous gel in aging and diabetes. Lysine-glucose generated
      Maillard products produced a decrease of viscosity and of the number average
      molecular weight (Mn) of hyaluronan during a 1 h incubation at 37 degrees C. This
      effect was comparable to that produced by 1 U/ml of testicular hyaluronidase but
      was weaker than the effect of a Fenton-type reagent (Udenfriend's reagent). The
      polydispersity of hyaluronan incubated with Maillard products appeared higher
      than with hyaluronidase suggesting a more random reaction. Antioxydant enzymes
      (SOD, catalase), the iron chelators (desferrioxamine, transferrin) and the free
      radical scavengers (uric acid, carnosine) inhibited the degradation by Maillard
      products confirming its free radical nature and the intervention of trace metals.
      Maillard products have been detected in diabetic vitreous and may play a role in
      its accelerated modifications (liquefaction) in diabetes as compared to normal
      aging.

PMID- 9513813
TI  - Evidence of molten globule like state(s) of interferon gamma in acidic and sodium
      perchlorate solutions.
AB  - Recombinant porcine interferon gamma (IFN gamma) at neutral pH is characterized
      by a tryptophan (Trp) fluorescence maximum around 343 nm and a rigid
      conformation, evidenced from tryptophan polarization values. Guanidine HCl shifts
      the protein emission spectra further to the red and decreases the fluorescence
      polarization values, indicating denatured IFN gamma in these solutions. In acidic
      solutions (3 < pH < 4), the emission spectra show a blue shift and lower
      tryptophan polarization. The midpoint of transition of these fluorescence
      properties occurs around pH 3.5-3.6. The protein in NaClO4 solution at neutral pH
      is similarly characterized by a blue shift in the tryptophan fluorescence maxima
      and low polarization values. The extent of quenching of tryptophan fluorescence
      by acrylamide is less in acid and in NaClO4 solutions of IFN gamma compared to
      its native form. This indicates a lower accessibility of the tryptophan in the
      altered conformation of the protein. The emission spectra of IFN gamma in NaClO4
      solution shows a decrease in the tryptophan fluorescence intensity with
      simultaneous shift of the emission spectra over time. The presence of two
      conformational forms of IFN gamma in perchlorate solution is evidenced from an
      isofluorescent point at 315 nm. The change in the conformational state in
      perchlorate solution is characterized by first order kinetics. The dye
      anilinonaphthalene sulfonic acid does not bind either to the native IFN gamma or
      to its denatured form. However, the dye binds to the acid form of IFN gamma, as
      well as when the protein is present in NaClO4 solution at neutral pH. These
      observations, together with the results from literature that IFN gamma retains
      its secondary structure in acid solution to a considerable degree, would suggest
      that the protein exists as a molten globule-like state in acidic solution.
      Similarities of the protein fluorescence and 1-anilino-8-naphthalene-sulfonic
      acid (ANS) binding properties of the protein in NaClO4 and acid solutions
      indicate that IFN gamma also exists in a molten globule-like state in perchlorate
      solution at neutral pH.

PMID- 9513814
TI  - Interaction between chitosan and uranyl ions. Part 2. Mechanism of interaction.
AB  - In this part of the study--understanding the mechanism of interaction between
      chitosan and uranyl ions, we confirmed the restrictive role of polymer
      crystallinity on uranyl sorption capacity. The saturation of the polymer by
      uranyl ions showed that approximately 1 mol of uranyl ions was sorbed for 2 mol
      of amino groups contained in the amorphous domain. This result can be related to
      the intrinsic properties of chitosan. Desorption experiments are in favour of
      strong interaction, in fact, no desorption was observed whatever the experimental
      conditions. Spectroscopic characterization was performed on complexes in solution
      and in the solid state. U.V.-visible spectrophotometric experiments showed that a
      unique type of complex was formed. FT-IR spectroscopy allowed us to observe the
      appearance of a new band at 1525 cm of amide II type and led us to conclude the
      formation of a unique complex by the coordination with chitosan amino groups.

PMID- 9513815
TI  - Effects of pH and salt environment on the association of beta-lactoglobulin
      revealed by intrinsic fluorescence studies.
AB  - The effects of pH, ionic strength and heat on the structure of beta-lactoglobulin
      (beta-lg) have been investigated by studying the intrinsic tryptophan
      fluorescence of the protein. Between pH 2 and 9, for sodium chloride
      concentrations varying from 0.0 to 0.2 M, the position of the fluorescence
      emission maximum at 20 degrees C remained constant at 328 nm, suggesting that the
      hydrophobic environment of the fluorophores remained unchanged. The fluorescence
      intensity increased significantly at pH 2, 7 and 9 on reducing the NaCl
      concentration of the solutions. The most likely explanation for this, supported
      by recent light scattering data, is that the presence of NaCl is necessary for
      beta-lg to dimerize. At the higher NaCl concentrations it was found that
      dimerization accompanied a reduction in fluorescence intensity. Thus,
      dissociation appears to reduce the self-quenching of tryptophan residues that
      occurs within the dimer. The fluorescence of solutions heated below the
      denaturation temperature reflected the state of association of the protein
      molecules. Above the denaturation temperature and associated with protein
      aggregation, an irreversible increase in intrinsic tryptophan fluorescence was
      observed. We also report what we believe to be the first front-face fluorescence
      measurements on globular protein gels, showing effects of pH and NaCl
      concentration.

PMID- 9513816
TI  - RGD sequences in several receptor proteins: novel cell adhesion function of
      receptors?
AB  - In the process of homology modelling of the 3-dimensional structure of alleles of
      the human histocompatibility protein HLA-DQ, we discovered that its RGD
      tripeptide (beta 167-169) forms part of a loop. A search through protein sequence
      data bases, revealed this cell adhesion motif in 67 integral plasma membrane
      proteins (in 48 extracellularly, and in the remaining 19 intracellularly), which
      are bona fide receptors, and none of them has thus far been considered as a cell
      adhesion protein. The 3-dimensional structure of one of these, the rat neonatal
      Fc receptor, is known and its extracellular RGD sequence is in an adhesion-like
      loop, a fact that went unnoticed in the original papers. In a few other cases,
      e.g. rat and mouse growth hormone receptor, and mouse CD40 ligand, homology
      modelling by ourselves and others reveals that the said sequences are part of a
      loop, in similarity to all RGD sequences found in proteins with established
      adhesion function and known 3-dimensional structure. Likewise, inspection of all
      known protein 3-dimensional structures containing an RGD sequence, and not having
      a documented cell adhesion function (total of 65 separate entries) shows that
      such sequence is mostly (52/65 or 80% of cases) part of a loop. We therefore call
      attention to these surprising findings, discuss the possible cell adhesion role
      of these receptor proteins, and draw an analogy from the two well characterised
      examples, that of soluble IGF binding protein 1 and the transcriptional activator
      protein Tat of HIV, where their RGD sequences have been shown by site-directed
      mutagenesis to participate in cell-adhesion interactions, without prior knowledge
      of the location of the tripeptide, or the 3-dimensional structure of the
      respective protein.

PMID- 9513817
TI  - Reversibility of heat-induced conformational changes and surface exposed
      hydrophobic clusters of beta-lactoglobulin: their role in heat-induced sol-gel
      state transition.
AB  - The effects of heat-treatment on the conformational changes of beta-lactoglobulin
      were monitored by differential scanning calorimetry (DSC), binding properties to
      1-anilino-8-naphthalenesulphonic acid (ANS) and to 5,5'-dithio-bis (2
      nitrobenzoic acid) (DTNB). The thermal transition of beta-lactoglobulin was 100%
      reversible on re-heating and its binding properties to the ANS fluorescent-dye
      and to the DTNB probe did not significantly change when the first heating was
      made to a temperature T < Tmax, that of the DSC maximal peak deviation of
      unheated solutions. When the solutions were heated to higher temperatures, the
      degree of reversibility of the thermal transition decreased, while the beta
      lactoglobulin surface hydrophobicity increased. Furthermore, the time (tg) needed
      for the sol-gel state transitions was highly temperature-dependent for the
      solutions showing no significant reactivity with the DTNB probe, a high
      percentage of residual tertiary structure but a low surface hydrophobicity. For
      beta-lactoglobulin showing < 50% residual tertiary structure but high surface
      hydrophobicity, tg values were hardly temperature-dependent. The results are
      discussed in terms of the role of hydrophobic interactions in the aggregation
      process of denatured beta-lg molecules.

PMID- 9513818
TI  - The diagnosis of inflammatory bowel disease--what should we tell the patient?

PMID- 9513819
TI  - Symptom evaluation for dyspepsia--promises and illusions.

PMID- 9513820
TI  - Diagnosis and treatment of paediatric Helicobacter pylori infection--are special
      guidelines needed?

PMID- 9513821
TI  - A validated dyspepsia symptom score.
AB  - BACKGROUND: The primary endpoint in clinical trials involving patients with non
      ulcer dyspepsia is subjective, i.e., reduction in symptomatology. Three
      attributes, reproducibility, responsiveness and validity, are necessary for the
      use of a symptom scoring system in a clinical trial. METHODS: The four most
      common symptoms in 50 dyspeptic patients were determined. To check the
      reproducibility of the symptom score, 48 patients and thirty control subjects
      were interviewed on two occasions (T0, T1), prior to any diagnostic or
      therapeutic intervention. Responsiveness was assessed by comparing the symptom
      scores of patients before (T0) and after (T2) treatment. Validity was assessed by
      comparing the symptom scores of dyspeptic patients to those of healthy volunteer
      subjects. RESULTS: Reproducibility The median T0 (16.00 and 6.90) and T1 (15.00
      and 6.56) scores of the patients and controls did not significantly vary during
      the one-week interval. Responsiveness The symptom scores at T0 had decreased at
      T2 for patients with gastro-oesophageal reflux (17.00 to 11.50, p = 0.0014), non
      ulcer dyspepsia where Helicobacter pylori was eradicated (16.00 to 7.00 p =
      0.0014), and duodenal ulceration (18.50 to 7.50, p = 0.0117) while there was an
      insignificant decrease (18.00 to 13.00, p = 0.0642) in non-ulcer dyspepsia
      patients who received a prokinetic agent. Validity The mean rank symptom score of
      74 patients (71.74) was significantly higher than that of the control population
      (26.83), (p = 0.0001). The mean time taken to perform the questionnaire was 3.6
      minutes. CONCLUSION: This questionnaire is suitable for the assessment of
      symptoms in patients with dyspepsia.

PMID- 9513823
TI  - Amoxycillin dual therapy against Helicobacter pylori--the final nail in the
      coffin?

PMID- 9513822
TI  - Dual therapy with high or low doses of omeprazole does not achieve an acceptable
      rate of Helicobacter pylori eradication in duodenal ulcer patients. A multicentre
      randomized long-term detailed study.
AB  - BACKGROUND: It has been reported that dual therapy with high doses of omeprazole
      and amoxycillin proves efficient for Helicobacter pylori eradication. AIM: To
      compare the efficacy, safety and tolerability of eradicating regimens with
      omeprazole/amoxycillin. METHODS: In this randomized multicentre study, 267
      duodenal ulcer patients were treated for 2 weeks with omeprazole 40 bid (Group A)
      or 20 mg bid (Group B), respectively, and with amoxycillin 0.5 g. qid followed by
      4 weeks of 20 mg omeprazole om. Helicobacter pylori status was assessed by both
      histology and urease test in the antrum and the corpus. The patients were then
      followed-up for 9 months. RESULTS: Helicobacter pylori infection was cured in
      62.9% of group A (95% CI: 53.8-71.4) and in 44.8% of group B (95% CI: 35.6-54.3;
      p = 0.007). Healing was achieved in 91.9% of patients in group A (95% CI:85.7
      96.1), and in 87.9% of patients in group B (95% CI:80.6-93.2). The estimated
      probability of being in ulcer remission for cured patients was 0.95 (95% CI: 0.90
      0.99) and for the not cured was 0.41 (95% CI: 0.24-0.59; p = 0.0001). However,
      between the two treatment groups no significant differences in symptom relief or
      ulcer recurrence were observed. Both regimens were well tolerated with minor side
      effects occurring likewise within the two groups. At two months in cured patients
      antral histology revealed a total (group A + B) prevalence of 13.7% of active
      chronic gastritis. CONCLUSIONS: This long-term, large-size study clearly
      indicates that dual therapy does not represent a truly effective eradication
      therapy and this regime cannot be recommended.

PMID- 9513824
TI  - Family treatment of symptomatic children with Helicobacter pylori infection.
AB  - BACKGROUND: Familial clustering of Helicobacter pylori infection has been
      reported. We tested the hypothesis that simultaneously treating all Helicobacter
      pylori positive family contacts of infected symptomatic children results in lower
      treatment failure. METHODS: Relatives of 47 children (index) with Helicobacter
      pylori gastritis had endoscopy to assess prevalence of infection in first degree
      cohabiting relatives. Controls included 60 children with dyspepsia and
      Helicobacter pylori gastritis whose infected family contacts were not treated.
      Index children, siblings younger than 18 years of age and control children
      received a 2-week course of amoxicillin and tinidazole. Parents of index children
      and their siblings over 18 years of age received a 2-week course of Colloidal
      Bismuth Subcytrate and tinidazole. The eradication rate in index children and
      their relatives was compared to controls whose infected family contacts were not
      treated. RESULTS: Helicobacter pylori was found in 67% of 31 siblings younger
      than 18, in 82% of 22 siblings older than 18 years, and in 87% of 92 parents.
      Endoscopy, repeated four to six weeks after the end of treatment, showed
      Helicobacter pylori eradication in 94% of children and siblings younger than 18,
      and in 70% of parents and siblings over 18 years in the family treatment group,
      compared with 75% of control children (p < .01). CONCLUSIONS: The high prevalence
      of the infection in family members suggests that person-to-person spread of
      Helicobacter pylori takes place. Furthermore our results show that if (or when)
      required, simultaneous treatment given to the whole family results in lower
      treatment failure, since it may promote compliance to treatment.

PMID- 9513826
TI  - Spondyloarthritis in patients with ulcerative colitis.
AB  - BACKGROUND: Extraintestinal manifestations can complicate the course of
      ulcerative colitis and can influence the prognosis. AIMS: Sixty-eight patients of
      the metropolitan area of Florence with ulcerative colitis in clinical and
      endoscopic remission were evaluated to establish the presence of
      spondyloarthritis. PATIENTS AND METHODS: Each patient was studied through
      clinical and radiological evaluations to assess the presence of joint
      involvement. RESULTS: We found signs of spondyloarthritis in 19 patients (27.9%).
      Four of them had a classic ankylosing spondylitis (5.8%) and in 3 of them the
      aplotype HLA B27 was present. Sacroileitis was found in 9 (13.2%) patients
      (monolateral in 5 cases and bilateral in 4). Six patients (8.8%) showed an
      unclassifiable form of arthritis, fulfilling the Amor criteria. In 13 of 19
      patients with spondyloarthritis, we found a pancolic extension of disease
      (68.4%). CONCLUSIONS: The results obtained from our series of ulcerative colitis
      patients reveal a lower proportion of cases of spondyloarthritis than that found
      in other Italian studies. We are planning further investigations on a larger
      population to better assess the prevalence of spondyloarthritis in ulcerative
      colitis patients.

PMID- 9513825
TI  - Histamine H2 receptor antagonist-refractory oesophagitis: the efficacy of long
      term omeprazole maintenance treatment.
AB  - BACKGROUND: Erosive oesophagitis refractory to high dose histamine H2 receptor
      antagonists (definition: failure to heal fully after > or = 3 months' treatment
      with cimetidine 3.2 g or ranitidine 0.9 g) responds well to omeprazole 40 mg
      daily but frequently relapses when the patients are put back on maintenance H2
      receptor antagonists at medium or even high dose (e.g. cimetidine 1.6 g and 3.2
      g, respectively). AIM: To investigate the efficacy of maintenance omeprazole 20
      mg daily in refractory erosive oesophagitis. PATIENTS & METHODS: In this open,
      sequential study, patients with H2 receptor antagonist-refractory oesophagitis
      were healed on omeprazole 40 mg daily and then put on maintenance H2 receptor
      antagonists (cimetidine 1.6 g or 3.2 g). Relapses were re-treated with omeprazole
      40 mg; upon rehealing, patients were put on maintenance omeprazole 20 mg daily
      for up to 4.5 years. RESULTS: Healing on omeprazole occurred in 38 out of 39
      patients (97%) at 12 weeks. Only six of the 38 patients (16%) relapsed
      (asymptomatic in half) during subsequent maintenance treatment, whereas all had
      relapsed earlier on high dose H2 receptor antagonists. CONCLUSION: Within the
      limits of interpretation of an open study, omeprazole 20 mg daily seems effective
      in maintaining prolonged remission in this group of patients with H2 receptor
      antagonist-refractory oesophagitis.

PMID- 9513827
TI  - Disease history in 382 Italian patients with Crohn's disease.
AB  - AIMS: This large-scale study was aimed at evaluating the long-term history of
      Crohn's disease in a cohort of consecutive patients referred to the Careggi
      Hospital in Florence from January 1973 to June 1996. PATIENTS: A total of 382
      patients (187 females, 195 males; mean age of 47 years) were included in our
      study. The median follow-up was more than 11 years and only 46 patients (12%) had
      a follow-up of less than 1 year. The main endpoints evaluated in these patients
      included mortality for any cause, disease-specific mortality, recurrences, and
      need for surgery. Furthermore, in a subgroup of 130 patients observed during the
      last 6 months of our study, a more detailed assessment of the disease was carried
      out in which the distribution of inflammatory, fibrostenosing and fistulizing
      forms was determined. RESULTS: Our results showed that the disease-specific
      mortality rate was extremely low (around 3% at 10 years and 5% at 20 years), but
      the rate of recurrence was approximately 50% at 3 years and more than 60% at 6
      years. Surgery was needed in more than 50% of the patients over the 10 years
      following diagnosis, and the risk of a second operation was of a further 30%
      within 4 years of the first operation. CONCLUSIONS: These epidemiological data
      emerging from our study are interesting since a large patient population was
      evaluated and the duration of the follow-up is extremely long.

PMID- 9513828
TI  - Portal hypertensive gastropathy: reproducibility of a classification, prevalence
      of elementary lesions, sensitivity and specificity in the diagnosis of cirrhosis
      of the liver. A NIEC multicentre study. New Italian Endoscopic Club.
AB  - OBJECTIVE: To classify elementary endoscopic lesions of portal hypertensive
      gastropathy, assess their reproducibility, prevalences, sensitivity and
      specificity in the diagnosis of cirrhosis of the liver. METHODS: 1) A
      classification of portal hypertensive gastropathy elementary lesions was defined.
      2) Thirty-two endoscopists evaluated videotapes of endoscopic examinations of
      patients with liver cirrhosis to assess beyond-chance agreement (kappa). 3)
      Fifteen centres enrolled consecutive patients with or without cirrhosis of the
      liver and recorded portal hypertensive gastropathy pattern according to its
      location. RESULTS: 1) Four elementary lesions (Mosaic-Like Pattern, Red Point
      Lesions, Cherry Red Spots, Black-Brown Spots) were identified, and graded. 2) A
      fair to good beyond-chance agreement was obtained for all 4 lesions. 3) portal
      hypertensive gastropathy prevalence was higher in patients with cirrhosis of the
      liver (0.63, sensitivity) than in controls (0.17). Mosaic-like pattern was the
      most prevalent sign (0.54). Specificity of portal hypertensive gastropathy was
      0.83. Portal hypertensive gastropathy was tentatively classified as mild or
      severe when mosaic-like pattern alone or red marks of any kind were present,
      respectively; this classification led to a further improvement in
      reproducibility. CONCLUSIONS: Our results suggest that a sufficient degree of
      agreement can be achieved in recording portal hypertensive gastropathy.
      Therefore, the New Italian Endoscopic Club classification should be used to
      evaluate the natural history of this condition.

PMID- 9513829
TI  - Portal hypertensive gastropathy--an elusive disorder?

PMID- 9513830
TI  - High prevalence of hepatitis C virus type 1b in Italian patients with Porphyria
      cutanea tarda.
AB  - BACKGROUND: A strong association between sporadic porphyria cutanea tarda and
      chronic hepatitis C virus infection was recently described in Italy, France and
      Spain. AIMS: To explore whether hepatitis C virus genotype plays a role in
      porphyria cutanea tarda complicating chronic hepatitis C. PATIENTS: Forty-seven
      hepatitis C virus-positive porphyria cutanea tarda patients and a control group
      of 45 patients of similar age with hepatitis C virus-associated chronic liver
      disease. METHODS: Comparison of frequency of hepatitis C virus genotypes in the
      two groups and in relation to the age of patients, hepatic histopathology and
      with the presence of other factors potentially able to trigger porphyria cutanea
      tarda. RESULTS: A single genotype, hepatitis C virus 1b, was found to be present
      in nearly 90% of porphyria cutanea tarda-associated chronic liver disease,
      significantly exceeding the frequency of the same genotype in the control group
      (p = 0.0001). The presence of hepatitis C virus 1b was not related to the age of
      patients or disease severity as evaluated by hepatic histopathology. CONCLUSIONS:
      Hepatitis C virus-associated chronic hepatitis found in the majority of Italian
      patients with porphyria cutanea tarda is usually sustained by hepatitis C virus
      genotype 1b. This viral strain might have a direct pathogenic role in inducing
      porphyria cutanea tarda or could increase the susceptibility of patients of other
      triggering factors such as iron overload or alcohol abuse.

PMID- 9513832
TI  - Serum C-reactive protein in acute biliary pancreatitis. Is it a reliable marker
      for the early assessment of severity of the disease?
AB  - BACKGROUND: The cut-off point of serum C-reactive protein to differentiate the
      mild from the severe form of acute pancreatitis is still debated; data concerning
      the C-reactive protein pattern in assessing the severity of acute biliary
      pancreatitis are lacking. AIM: To define the best cut-off point in
      differentiating the severe from the mild form of acute biliary pancreatitis.
      PATIENTS: Fifty patients with acute biliary pancreatitis: 34 patients with mild
      pancreatitis and 16 with the severe form of the disease were studied. METHODS:
      Serum C-reactive protein concentrations were assessed in all patients upon
      admission and for the following 5 days. RESULTS: No significant difference in
      serum C-reactive protein levels was found in the first 2 days in patients with
      mild pancreatitis compared to those with the severe form of the disease. Using a
      cut-off point of 11 mg/dl, the sensitivity of serum C-reactive protein in
      assessing the severity of acute pancreatitis during the first two days of the
      study was 9% and 57%, the specificity, 93% and 81%, and the accuracy 71% and 74%,
      respectively. CONCLUSIONS: Serum determination of C-reactive protein in the first
      48 hours of the disease is not a reliable marker of the severity of acute biliary
      pancreatitis.

PMID- 9513831
TI  - Power Doppler sonography to evaluate response to percutaneous ethanol injection
      in hepatocellular carcinoma.
AB  - BACKGROUND AND AIMS: The aim of the present study was to compare power Doppler
      imaging with traditional color Doppler imaging and with contrast enhanced
      computer tomography in the evaluation of intratumoral vascularity of
      hepatocellular carcinomas at diagnosis and in response to percutaneous ethanol
      injection. PATIENTS AND METHODS: Sixteen patients with hepatocellular carcinoma
      underwent colour Doppler, power Doppler and computed tomography at diagnosis.
      Seventeen patients were studied by the three techniques one month after
      percutaneous ethanol injection treatment. RESULTS: At baseline evaluation, power
      Doppler and color Doppler were always in agreement and, with the exception of one
      case, were also in agreement with the computerized tomography scan. On the
      contrary, power Doppler and computerized tomography are more sensitive than color
      Doppler in the evaluation of residual vascularized tumoral tissue after
      percutaneous ethanol injection. In 3 patients, residual vascularity was
      demonstrated only by computerized tomography while color and power Doppler were
      negative. In another 3 cases, a positive power Doppler signal, with a typical
      arterial Doppler spectrum, was observed while color Doppler and computerized
      tomography were negative. In these patients, cancer relapse was clinically
      evident after a few months and treatment was repeated to obtain complete
      necrosis. CONCLUSIONS: We conclude that only the integration of the results of
      all these techniques can reliably evaluate tumoral vascularity after percutaneous
      ethanol injection.

PMID- 9513833
TI  - Gastrointestinal autonomic nerve tumor of the jejunum. Case report and review of
      the literature.
AB  - Gastrointestinal autonomic nerve tumor is very rare and it is difficult to
      distinguish this tumor from other gastrointestinal tumors due to the absence of
      clinical, instrumental and macroscopic features which allow pre- or
      intraoperative diagnosis. Our aim was to recognize the characteristic features
      (preoperative, intraoperative, pathological) that would allow diagnosis of
      gastrointestinal autonomic nerve tumor. A case of gastrointestinal autonomic
      nerve tumor of the jejunum is reported. Surgical specimen was routinely
      processed. Immunohistochemical staining was performed according to modified
      immunoperoxidase Avidin-Biotin-Peroxidase Complex method. An electron microscopy
      study was also performed. The tumor mass showed some characteristic pathological
      findings: histologically, it was composed of spindle cells and epithelioid cells;
      immunohistochemically, a focal positivity for Neuron Specific Enolase was shown,
      and finally, ultrastructural examination showed neuron-like cells with long
      cytoplasmic processes containing microtubules and bulbouns synapse-like
      structures with dense core neurosecretory-type granules. Preoperatively
      gastrointestinal autonomic nerve tumor of the jejunum must be considered and
      treated as a malignant tumor. A correct diagnosis is possible only with
      immunohistochemical and ultrastructural studies. It is probable that this tumor
      is more common than previously thought.

PMID- 9513834
TI  - Oesophageal tuberculosis mimicking secondary oesophageal involvement of
      mediastinal neoplasm.
AB  - During the last decade the number of cases of abdominal tuberculosis diagnosed in
      Western countries has dramatically increased. There are many reasons, including
      the appearance of AIDS and the increased morbidity of people across the world due
      to the westward migration of many people coming from areas with a high incidence
      of tuberculosis. Oesophageal involvement is rare in tuberculosis, occurring
      mainly as an extension of the disease from the adjacent tuberculous lymph nodes.
      Fifty-eight cases of oesophageal tuberculosis have so far been reported. We
      describe a patient affected by oesophageal tuberculosis mimicking secondary
      oesophageal involvement of mediastinal malignancy.

PMID- 9513835
TI  - Should Helicobacter pylori be eradicated before starting long-term proton pump
      inhibitors?
AB  - Symptomatic gastro-oesophageal reflux disease is a common disorder characterized
      by pathological exposure of the distal oesophagus to acid. The management
      requires the control of symptoms, prevention of relapse and complications. Proton
      pump inhibitors are without doubt the most effective agents in the management of
      gastro-oesophageal reflux disease. In Helicobacter pylori-negative individuals
      the efficacy of ranitidine, but more pronounced of omeprazole, on the nocturnal
      intragastric acidity, is less than in Helicobacter pylori-positive patients.
      Curing the Helicobacter pylori infection in gastro-oesophageal reflux disease
      patients might, therefore, have the disadvantage of losing efficacy of
      antisecretory therapy. Conversely, several studies have shown that long-term use
      of proton pump inhibitors is associated with progression and worsening of body
      gastritis exclusively in Helicobacter pylori-positives. This observation makes
      Helicobacter pylori eradication indicated before starting long-term treatment
      with proton pump inhibitors for gastro-oesophageal reflux disease and other acid
      related diseases. The data reported, so far, however, are not conclusive. The
      Federal Drugs Administration Advisory Committee concluded on available data, that
      there is no evidence that longterm proton pump inhibitors treatment leads to
      gastric atrophy, intestinal metaplasia or gastric cancer. Eradication of
      Helicobacter pylori infection might lead to reduction in the efficacy of
      antisecretory agents, but might prevent worsening of the gastric corpus
      gastritis. More data are needed to really answer these clinically relevant
      questions.

PMID- 9513836
TI  - A growing demand for Helicobacter pylori culture in the near future?
AB  - Culture is the basic method in bacteriology. It allowed the discovery of
      Helicobacter pylori. Problems in the culture of this fragile, slow-growing
      bacterium concern transport and processing in the laboratory, but they can be
      solved. Culture has a 100% specificity. When performed properly, it has a
      sensitivity in the range of the other best diagnostic methods for Helicobacter
      pylori. It allows strain typing and, most importantly, susceptibility testing to
      antibiotics, because an increased rate of acquired resistance of Helicobacter
      pylori is currently observed. Culture must be performed in clinical trials, at
      least when antibiotics, to which Helicobacter pylori may be resistant, are used.
      In clinical practice, culture and susceptibility testing can generally be
      restricted to treatment failures. However, it is important to monitor
      Helicobacter pylori susceptibility to antibiotics at a national or regional level
      in order to give recommendations for primary treatment.

PMID- 9513837
TI  - Endoscopic diagnosis of oesophagitis: interobserver agreement beyond chance.

PMID- 9513838
TI  - AIDS-related chronic diarrhoea in a developing country. A retrospective study.

PMID- 9513839
TI  - Mixed cryoglobulinaemia and hepatitis C virus infection.

PMID- 9513840
TI  - One more case of hepatic injury due to amineptine.

PMID- 9513841
TI  - Importance of endometrial quality in women with tubal infertility during a
      natural menstrual cycle for the outcome of IVF treatment.
AB  - PURPOSE: The importance of endometrial maturation at estimated time of
      implantation for the outcome of IVF treatment in regularly menstruating women
      with tubal infertility was evaluated. METHODS: FSH was measured on cycle day 3,
      on days 10-15 urine and blood were collected to estimate the day of the LH peak,
      and E2 and P4 were measured during the luteal phase, on cycle days 19-26. An
      endometrial biopsy was obtained on days LH + 3 to LH + 6. RESULTS: The number of
      subjects with delayed endometrial maturation was larger in the group of infertile
      women who did not become pregnant compared to pregnant women and controls. Those
      infertile women who did not become pregnant after IVF treatment also presented
      with a higher basal FSH on cycle day 3 and lower E2 and P4 AUC in the luteal
      phase. Six infertile women and two controls presented with mid- and late
      proliferative endometrium in the luteal phase on cycle days LH + 3 to LH + 6, in
      the presence of adequate E2 and P4 secretion. Six morphological characteristics
      were compared in the three groups: (1) 17 infertile women who became pregnant,
      (2) 18 who did not become pregnant, and (3) 28 controls. The pregnant infertile
      women did not differ from the controls. The numbers of glandular and stromal
      mitoses were significantly higher in those women who did not become pregnant (P <
      0.01) compared with those who became pregnant. Endometrial biopsies obtained on
      cycle days LH + 5 and LH + 6 showed significant differences in glandular
      epithelial height (P < 0.05) and number of vacuolated cells among the nonpregnant
      women (P < 0.01), the pregnant women (P < 0.05), and controls. CONCLUSIONS: A
      higher frequency of retarded endometrial development in women who did not become
      pregnant following IVF treatment was found. In some cases, endometrial
      insensitivity could most likely cause retarded endometrial development and
      failure of implantation after IVF treatment, which could not be overcome by
      routine luteal-phase support. However, our results do not allow conclusions
      concerning its relative importance compared to preembryo quality; this has to be
      investigated further.

PMID- 9513842
TI  - Assisted hatching does not enhance IVF success in good-prognosis patients.
AB  - PURPOSE: The role of assisted hatching in good-prognosis IVF patients was
      evaluated in a prospective, randomized, controlled pilot study, which was
      followed by a retrospective observational series. METHODS: After assisted
      hatching was proved successful in a mouse embryo study, 20 good-prognosis IVF
      patients were randomly assigned to either assisted hatching (13) or no assisted
      hatching (7; the controls). Following this series, 27 good-prognosis IVF patients
      were retrospectively evaluated to determine the outcome with assisted hatching.
      RESULTS: In the prospective study, clinical pregnancies resulted from 3 (23%) of
      13 patients in the hatching group, compared to 3 (43%) of 7 in the control group.
      Implantation rates were similar: 9.6% in the hatching group and 10.7% in the
      controls. In the retrospective series, the 11.1% implantation rate with assisted
      hatching was significantly less than the 42.9% implantation rate seen with
      traditional IVF. CONCLUSIONS: Implantation and pregnancy rates are high in young
      women undergoing traditional IVF. Assisted hatching is not beneficial in these
      patients.

PMID- 9513843
TI  - Comparison of highly purified FSH (metrodin-high purity) with pergonal for IVF
      superovulation.
AB  - PURPOSE: The use of highly purified follicle-stimulating hormone (Metrodin-HP)
      was compared with that of a preparation containing follicle-stimulating hormone
      and luteinizing hormone (Pergonal) for production of superovulation in an IVF
      program. METHODS: We used the Oxford Fertility Unit database to identify patients
      undergoing their first cycle of IVF, using either Metrodin-HP or Pergonal.
      Patients were treated with a standardized drug protocol and were stratified by
      age and cause of infertility. Ovarian stimulation with either Metrodin-HP (Serono
      Laboratories) or human menopausal gonadotropin (hMG; Pergonal; Serono
      Laboratories) after pituitary desensitization commenced in the midluteal phase of
      the preceding cycle. Monitoring was performed by ultrasound and serum estradiol
      measurement prior to transvaginal oocyte recovery, followed by IVF and transfer
      of no more than three embryos. RESULTS: For Metrodin-HP versus Pergonal, the
      rates of egg retrieval (98 vs 94%), fertilization (89 vs 92%), clinical pregnancy
      (32.9 vs 23.4%), miscarriage (4.1 vs 4.5%), live birth (26 vs 18.5%), and ovarian
      hyperstimulation syndrome (5.5% vs 5.9%) were similar in both groups. The
      apparent increase in clinical pregnancy and live birth with Metrodin-HP did not
      reach statistical significance. The dosages of gonadotropins used were
      comparable. Estradiol levels measured on day 8 of stimulation were significantly
      lower in the Metrodin-HP group than in the Pergonal group, but the difference did
      not reach statistical significance on the day of hCG administration.
      Significantly more follicles (greater than 12 mm) were obtained in the Metrodin
      HP group, but the numbers of eggs recovered and fertilized were similar in the
      two groups. CONCLUSIONS: These findings demonstrate that highly purified FSH
      (Metrodin-HP) is as effective and successful as hMG (Pergonal) for ovarian
      stimulation in a standard IVF regimen. Exogenous luteinizing hormone (LH) is not
      required for satisfactory ovarian stimulation in IVF. Measurement of estradiol
      may be less helpful in the monitoring of Metrodin-HP cycles, but the level
      reached on the day of hCG administration can still be used to predict, and hence
      avoid, ovarian hyperstimulation syndrome.

PMID- 9513845
TI  - Management of transient ovarian failure: pregnancy after in vitro fertilization
      and intracytoplasmic sperm injection--a case report.
AB  - PURPOSE: The case history of a 36-year-old patient with transient ovarian
      failure, presumably induced by previous ovarian surgery and a recent pelvic
      inflammatory disease, is described. METHODS: During several months, the patient
      underwent transvaginal ultrasound and hormonal follow-up. Ovulation was triggered
      by hCG in a cycle in which spontaneous follicular ripening had occurred.
      Transvaginal puncture of the single follicle was performed for in vitro
      fertilization. RESULTS: One oocyte was retrieved and fertilized by
      intracytoplasmic sperm injection, giving rise to a single good-quality embryo. A
      singleton pregnancy, which ended in the birth of a healthy daughter, was
      established. CONCLUSIONS: This case demonstrates that it is worthwhile to monitor
      patients with transient ovarian failure closely, and if other infertility factors
      are present, IVF of one oocyte may be considered.

PMID- 9513846
TI  - Is there any need for diagnostic laparoscopy in couples undergoing
      intracytoplasmic sperm injection for severe male-factor infertility.
AB  - PURPOSE: Our purpose was to determine whether there is a need for a preliminary
      diagnostic laparoscopy in couples undergoing intracytoplasmic sperm injection
      (ICSI) because of severe male-factor infertility. METHODS: In this retrospective
      study, the results of diagnostic laparoscopy in 342 women with a normal fertility
      workup undergoing ICSI were evaluated and sperm parameters were correlated with
      the findings at laparoscopy. Subgroups of patients were defined according to
      sperm quality, which was expressed as total normal motile count [TNMC = volume
      (ml) x concentration (10(6)/ml) x percentage progressive motility/100 x
      percentage normal morphology/100]. RESULTS: When sperm morphology was evaluated
      according to Kruger's strict criteria, the probability of finding pathology on
      laparoscopy in the normal male group (16.7%) was statistically higher than that
      in the group with severely abnormal sperm (1.8%; P < 0.01). CONCLUSIONS: There is
      no need to perform a preliminary diagnostic laparoscopy in the female partner if
      a full workup is normal in couples with severe male-factor infertility willing to
      undergo ICSI.

PMID- 9513844
TI  - Zona pellucida thickness variation and occurrence of visible mononucleated
      blastomers in preembryos are associated with a high pregnancy rate in IVF
      treatment.
AB  - PURPOSE: The ability of six morphological criteria (embryo development rate,
      fragmentation, regularity of blastomere shape, equality of blastomere size, zona
      pellucida thickness variation [ZPTV], and visible mononucleated blastomeres
      [VMBs]) to predict pregnancy in IVF treatment cycles was evaluated. METHODS: In
      order to select a homogeneous study group, 85 consecutive nulliparous couples
      with single tubal infertility undergoing their first IVF treatment and receiving
      three preembryos at embryo replacement 2 days after ovum pickup were included.
      RESULTS: A total of 255 preembryos was replaced two days after ovum pickup and
      resulted in 34 clinical pregnancies (40%). By logistic regression analysis, ZPTV
      and VMBs showed highly significant and strong predictive values, whereas none of
      the other parameters was a significant predictor of pregnancy. In the treatments
      in which all replaced preembryos had a ZPTV of less than 15%, the pregnancy rate
      was extremely low (1/22). If the maximum ZPTV of any of the replaced preembryos
      was in the interval between 15 and 20%, the pregnancy rate was 24.1% (7129). In
      the treatments in which at least one preembryo had a ZPTV of more than 20%, the
      pregnancy rate was 76.5% (26/34). When VMBs were added to the results of the ZPTV
      analysis, the pregnancy rate was as high as 92.3% (24/26). CONCLUSIONS: ZPTV and
      VMBs seem to be strong predictors of pregnancy in IVF treatment and thus
      important indicators of good embryo quality.

PMID- 9513847
TI  - Spontaneous and follicular fluid-induced acrosome reaction in sperm samples from
      in vitro fertilizing and nonfertilizing normozoospermic patients.
AB  - PURPOSE: One of the most challenging and intriguing groups of infertile patients
      is that of normozoospermic men who have repeatedly not achieved fertilization in
      vitro. These cases probably present a wide range of gamete disorders manifested
      at different stages of the fertilization process. The occurrence of spontaneous
      and follicular fluid (FF)-induced acrosome reactions (ARs) in in vitro
      fertilizing and nonfertilizing specimens from normozoospermic IVF patients was
      assessed, and the effect of Percoll and cryopreservation on the incidence of ARs
      was evaluated. METHODS: Semen samples from 62 normozoospermic (15 in vitro
      nonfertilizing and 47 fertilizing) patients were analyzed. Spermatozoa were
      double-stained with FITC-conjugated Pissum sativum lectin, to assess their
      acrosomal status, and propidium iodide, to evaluate their vitality, using flow
      cytometry analysis. RESULTS: A lower average of AR incidence was observed in the
      nonfertilizing than in the fertilizing group with all treatments. Both groups
      exhibited an increase in the proportion of ARs following incubation with FF. This
      rise was most prominent when Percoll-separated fractions were used (15.8 and
      25.6% AR in the nonfertilizing and fertilizing groups, respectively). Thawed
      cryopreserved and fresh fertilizing samples exhibited similar AR rates.
      CONCLUSIONS: That normozoospermic recurrently nonfertilizing compared to
      fertilizing semen samples have a lower capacity to undergo ARs is suggested.

PMID- 9513850
TI  - Interovarian differences in levels of cotinine, a major metabolite of nicotine,
      in women undergoing IVF who are exposed to cigarette smoke.
AB  - PURPOSE: Our purpose was to determine whether there is variation in levels of
      follicular fluid (FF) cotinine between the two ovaries of women undergoing IVF-ET
      who are exposed to cigarette smoke. METHODS: In 61 women, there were two to four
      determinations of FF continine levels for each of two follicles, one from each
      ovary. For each woman a t test for significant difference between the means of
      both ovaries was done to test for interovarian variation. RESULTS: Thirty-seven
      nonsmokers, 8 passive smokers, and 16 active smokers differed greatly (P <
      0.0001) in mean FF cotinine levels: 13.0, 91.1, and 420.3 ng/ml, respectively.
      Fourteen women had significant differences, at the P = 0.025 level or below,
      between their two ovaries. Five of them had differences significant at the 0.001
      level. Even so, the correlation between the cotinine levels of the two ovaries
      was high. CONCLUSIONS: Cotinine uptake between the two ovaries of a woman may
      differ approximately one-fourth of the time. In spite of these differences, the
      overall correlation between ovaries is high. The clear distinction in levels of
      FF cotinine among active, passive, and nonsmokers demonstrates the reliability of
      FF cotinine testing. Detection of cotinine in a large proportion of nonsmokers
      shows how pervasive nicotine is in the environment.

PMID- 9513851
TI  - Reinnervation reexamination.

PMID- 9513848
TI  - Effect of pentoxifylline on immotile testicular spermatozoa.
AB  - PURPOSE: A model for differentiating live and dead sperm cells during
      intracytoplasmic sperm injection (ICSI) is proposed. METHODS: We used
      pentoxifylline, a phosphodiesterase inhibitor known to enhance sperm motility, to
      initiate motility in testicular spermatozoa. Ten immotile testicular sperm
      samples were divided into two parts for examination of sperm motility with and
      without pentoxifylline treatment at 30, 60, and 90 min. RESULTS: The samples
      without pentoxifylline remained immotile even after 90 min of incubation: the
      addition of pentoxifylline initiated sperm motility in all samples: 51.8 +/-
      10.2, 64.4 +/- 9.4, and 70.8 +/- 8.9% (mean +/- SD) at 30, 60, and 90 min,
      respectively. CONCLUSIONS: That pentoxifylline may be used to differentiate live
      testicular spermatozoa during ICSI, which may improve fertilization and pregnancy
      rates, is suggested.

PMID- 9513849
TI  - Cytokines in the human ovary: presence in follicular fluid and correlation with
      leukotriene B4.
AB  - PURPOSE: This study was undertaken to correlate the follicular levels of
      interleukin (IL)-1 alpha, IL-2, tumor necrosis factor-alpha (TNF-alpha), and
      leukotriene (LT) B4 with oocyte maturity, fertilization, and achievement of
      pregnancy. METHODS: The material was obtained from 22 women undergoing IVF, 8 of
      whom became pregnant and 14 of whom did not. RESULTS: All of the studied
      cytokines and LT B4 were found in follicular fluids, but there were no
      significant differences according to oocyte maturity, fertilization, embryo
      quality, and achievement of pregnancy. On the other hand, a significant positive
      correlation was found between IL-1 alpha and TNF-alpha, IL-1 alpha, and LT B4 as
      well as between TNF-alpha and LT B4 in follicular fluids with subsequently
      fertilized oocytes. CONCLUSIONS: It seems that IL-1 alpha, TNF-alpha and LT B4
      may take part in the process of follicle wall degradation, and their follicular
      correlations may suggest more optimal follicular and oocyte development and
      maturation.

PMID- 9513852
TI  - Diastolic properties, myocardial water content, and histologic condition of the
      rat left ventricle: effect of varied osmolarity of a coronary perfusate.
AB  - BACKGROUND: Although myocardial edema is known to impair diastolic filling of the
      left ventricle, the interrelation of edema, histologic condition, and function
      has not been quantitated sufficiently for extrapolation to studies of
      multifactorial influences on diastolic properties. METHODS: Accordingly, ACI rat
      hearts arrested at 4 degrees C underwent coronary artery perfusion with a
      cardioplegia solution that was either unaltered (288 mOsm/L, P288 group, n = 6),
      diluted (144 mOsm/L, P144 group, n = 6), or concentrated (380 mOsm/L, P380 group,
      n = 6). Postmortem left ventricular pressure-volume curves and myocardial water
      content were measured. Myocardial samples were fixed in varying dilutions of
      glutaraldehyde. After dehydration and paraffin embedding, edema was graded
      subjectively (0 to 5), and myocardial interstitial spaces were determined by use
      of a semiquantitative method. RESULTS: Mean normalized left ventricular filling
      volume at 20 mm Hg filling pressure in the P144 group, 189 +/- 16 microliters
      (SEM), was reduced versus both the P288 (278 +/- 26 microliters) and the P380
      (332 +/- 18 microliters) groups (p < 0.05, ANOVA). Mean myocardial water content
      in the P144 group, 80.7% +/- 1%, was increased versus the P380 (76.7% +/- 0.4%, p
      < 0.05) but not versus the P288 group (78.4% +/- 0.8%). In hearts preserved with
      2.5% glutaraldehyde, mean edema grade and interstitial space in the P144 group
      (4.0 +/- 0.3) were increased versus the P380 (1.8 +/- 0.3, p < 0.05) but not the
      P288 group (2.7 +/- 0.5). Derived linear regressions relate water content to
      filling volume and histologic condition. CONCLUSIONS: Coronary perfusate
      osmolarity is thus associated with predictable changes in myocardial water
      content, left ventricular filling volume, and edema. These correlations allow
      definition of new hypotheses for the study of cardiac allograft rejection in
      patients and experimental animals.

PMID- 9513853
TI  - Cyclosporine dosage can be reduced when used in combination with an anti
      intercellular adhesion molecule-1 monoclonal antibody in rats undergoing
      heterotopic heart transplantation.
AB  - BACKGROUND: Intercellular adhesion molecule-1 (ICAM-1) is believed to play a role
      in acute rejection of allografted tissues. This molecule is involved in the
      interaction of T cells with antigen-presenting cells expressed on the vascular
      endothelium of transplanted organs and is involved in the adhesion of
      inflammatory cells to this endothelium and their subsequent migration into the
      underlying tissues. METHODS: Rat abdominal heterotopic heart transplantation was
      used to study the role of ICAM-1 in the rejection process. American Cancer
      Institute rats were used as donors; Lewis rats were used as recipients. Graft
      survival was monitored daily via donor heart palpation. Nine groups (n = 6/group)
      were studied: untreated controls; olive oil; cyclosporine at 1.5, 2.75, and 5.0
      mg/kg, respectively; R3.1, a control monoclonal antibody; 1A29, a rat anti-ICAM-1
      monoclonal antibody, 3 mg/kg administered intraperitoneally; a combination of
      1A29 (3 mg/kg) and cyclosporine (1.5 mg/kg); and a combination of 1A29 (3 mg/kg)
      and cyclosporine (2.75 mg/kg). RESULTS: Mean rejection time was 8.8 +/- 0.6 days
      for the untreated allografted controls and 9.7 +/- 1.1 days for the olive oil
      controls. Cyclosporine (1.5, 2.75, and 5.0 mg/kg) showed mean rejection times of
      8.5 +/- 0.3, 20.5 +/- 1.9, and 28.8 +/- 3.6 days, respectively. The 1A29
      treatment showed a mean rejection time of 9.3 +/- 0.7 days. Combination therapy
      of 1A29 and cyclosporine at 1.5 or 2.75 mg/kg demonstrated mean rejection times
      of 17.7 +/- 3.3 and 29.2 +/- 6.7 days, respectively. Thus 1A29 alone does not
      prolong cardiac allograft survival; however, combination therapy with either a
      subthreshold or a moderate dose of cyclosporine significantly extends the time to
      rejection of heterotopically transplanted rat hearts. CONCLUSIONS: Although
      monotherapy with an ICAM-1 antagonist alone may not be beneficial in preventing
      acute rejection episodes after organ transplantation, combination therapy of an
      anti-ICAM-1 monoclonal antibody may allow for a reduction in the dose of
      cyclosporine necessary for immune suppression. Such a reduction could lead to a
      lowering of the incidence of nephrotoxicity and other side effects associated
      with long-term cyclosporine administration.

PMID- 9513854
TI  - Transmission of hepatitis B virus among heart transplant recipients during
      endomyocardial biopsy procedures.
AB  - BACKGROUND: The unexpected conversion to HBsAg seropositivity of three cardiac
      allograft recipients prompted us to conduct a multidisciplinary study to identify
      the source, transmission mode, and extent of the hepatitis B virus (HBV)
      infection among the 256 cardiac allograft recipients of our hospital. METHODS:
      All recipients were retrospectively screened for serum markers of HBV infection.
      A selected genomic region defining subtypes of the viruses involved was amplified
      and sequenced. An epidemiologic case-control study for possible risk factors was
      conducted to identify the mode of transmission. RESULTS: Eighteen additional HBV
      infected patients were identified, none of whom had shown symptoms of HBV
      infection. The involvement of one virus (subtype ayw 3) was shown in 20 of the 21
      HBV-infected patients. This virus is found in less than 10% of HBV-infected
      individuals in The Netherlands. The demonstration of a common source of
      infection, combined with results of the epidemiologic study, identified
      posttransplantation endomyocardial biopsy procedures as the most likely mode of
      transmission. However, we also found evidence of secondary virus transmission by
      cardiac catheterization procedures to nonallograft recipients. CONCLUSIONS: The
      immunosuppressive therapy practiced in these patients to prevent allograft
      rejection may have not only facilitated virus transmission by causing high levels
      of viremia but also left the spreading of HBV undetected by causing a subclinical
      course of the infection. These findings stress the necessity of strict hygienic
      precautions during intravascular diagnostic procedures and indicate that
      vaccination against and routine monitoring for certain bloodborne infections in
      cardiac allograft recipients should be considered.

PMID- 9513855
TI  - Endothelin participates in increased circulating atrial natriuretic peptide early
      after human heart transplantation.
AB  - BACKGROUND: Hemodynamic improvement after heart transplantation is expected to
      normalize the neuroendocrine balance, but circulating atrial natriuretic peptide
      (ANP) remains elevated. Endothelin stimulates ANP secretion and its concentration
      increases after heart transplantation, suggesting a role for this peptide in the
      cardiovascular adaptative response to heart transplantation. METHODS: To
      investigate whether endothelin may induce ANP increase in heart transplant
      recipients, we monitored daily ANP, endothelin, and related hormonal, biologic,
      and hemodynamic parameters before and during the first week after either heart
      transplantation (n = 15) or coronary artery bypass grafting (n = 10). RESULTS:
      Surgery induced a transient secretory peak of arginine vasopressin and endothelin
      in both groups at day 1. Bypass grafting did not modify normal ANP (11.8 +/- 2.1
      pmol/L), endothelin (2.4 +/- 0.3 pmol/L), renin activity (0.11 +/- 0.04
      pmol/L/sec), or aldosterone (492 +/- 122 pmol/L) values. Heart transplantation
      normalized the renin-aldosterone axis, but the early decrease observed for ANP
      (from 27.2 +/- 4.8 to 21.14 +/- 1.4 pmol/L) was only partial and transient.
      Endothelin further increased (from 4.4 +/- 0.8 to 9.14 +/- 1.8 pmol/L; p < 0.01)
      after transplantation. Positive correlations were observed between endothelin,
      isoproterenol dose, creatinine, right atrial pressure, and ANP, but multiple
      correlation analysis showed the important role of endothelin (r = 0.69, p <
      0.001). Cyclic guanosine monophosphate correlated with ANP (r = 0.65, p < 0.001).
      CONCLUSIONS: Elevated endothelin, suggesting vascular dysfunction, likely
      contributes to the ANP increase observed early after heart transplantation.
      Furthermore, ANP, through a cardiac endothelium feedback, may act in the
      maintenance of circulatory homeostasis in heart transplant recipients.

PMID- 9513856
TI  - Noninvasive detection of allograft rejection in heart transplant recipients by
      use of Doppler tissue imaging.
AB  - BACKGROUND: Allograft rejection in heart transplant recipients is associated with
      lymphocytic extracellular infiltration and edema resulting in increased
      myocardial stiffness and abnormal relaxation. We hypothesize that these
      abnormalities will result in reduced myocardial relaxation velocities. Doppler
      tissue imaging is a novel noninvasive imaging modality that is capable of
      quantifying myocardial tissue velocities and may therefore be useful to identify
      allograft rejection. METHODS: In this observational study, 121 heart transplant
      recipients underwent pulsed-wave Doppler tissue imaging at the time of their
      surveillance endomyocardial biopsies. Peak relaxation and systolic velocities
      were measured from the inferior wall blinded to clinical biopsy. Biopsy results
      were classified as rejecting (3a, 3b, 4) or nonrejecting (0, 1a, 1b). RESULTS:
      The peak relaxation velocity in nonrejecting allograft recipients (n = 98) was
      0.21 m/sec +/- 0.01. During moderate allograft rejection (n = 16), peak
      relaxation velocities decreased to 0.14 m/sec +/- 0.01 (p < 0.0001), and
      subsequently increased to 0.23 m/sec +/- 0.0 after successful treatment (p =
      0.0001). Peak systolic velocities did not change during rejection, 0.08 m/sec +/-
      0.02 when compared with nonrejecting recipients 0.09 +/- 0.02 (p = NS). With a
      cutoff value of less than 0.16 m/sec, the sensitivity of peak myocardial
      relaxation velocities for detection of rejection was 76%. The specificity and
      negative predictive values were 88% and 92%, respectively. CONCLUSION: Moderate
      allograft rejection results in reduced myocardial relaxation velocities, which
      can be detected noninvasively with pulsed-wave Doppler tissue imaging. Hence,
      Doppler tissue imaging is a useful noninvasive tool to exclude allograft
      rejection.

PMID- 9513857
TI  - Central nervous system complications after lung transplantation.
AB  - PURPOSE: This study describes the central nervous system (CNS) events after lung
      transplantation. METHODS: A chart review of all lung transplant recipients (LTR)
      to collect the clinical and neuroimaging data for CNS events defined as seizures,
      severe headaches, confusion, or stroke. RESULTS: Twenty-six patients of 100 LTRs
      from 1990 through 1995 had a CNS event; more than one event occurred in 5
      patients for a total of 32 events. Severe headache was most common, occurring in
      14 patients, followed by seizures in 10, stroke in 5, and confusion in 3. The CNS
      event was related to infection in three of the 26 patients. Of all evaluations
      performed, magnetic resonance imaging (MRI) identified the most abnormalities,
      the most common being white matter changes consistent with cyclosporine toxicity.
      Cyclosporine levels were elevated in slightly more than half of the patients.
      Hypomagnesemia was present in three of 10 patients with seizures. Prognosis for
      recovery from these complications was good, with only five patients having
      ongoing problems with headaches, one requiring long term anticonvulsant therapy,
      three having minor or no limitations from stroke and no long-term problems with
      confusion. One patient with seizures resulting from an aspergilloma died.
      CONCLUSION: CNS events occur commonly in LTRs, mostly related to cyclosporine
      toxicity or infection. MRI identifies more abnormalities than computed
      tomography. These events were not consistently associated with documented high
      cyclosporine levels and hypomagnesemia. In spite of significantly abnormal MRIs,
      the functional outcome is favorable.

PMID- 9513858
TI  - Single lung transplantation for emphysema: predictors for native lung
      hyperinflation.
AB  - BACKGROUND: Single lung transplantation is an established procedure for the
      treatment of respiratory failure resulting from emphysema. Initial concerns
      suggested that ventilation/perfusion mismatch may result in an unsatisfactory
      outcome, but good clinical results proved those concerns to be unfounded.
      However, a proportion of patients have had development of native lung
      hyperinflation (NLH), with increased morbidity and mortality rates. This study
      was undertaken to evaluate the factors that might predict those patients with
      emphysema who are at greatest risk for development of NLH. METHODS: We
      retrospectively analyzed data from 27 patients who underwent 31 single lung
      transplantations for emphysema. The patients were divided into two groups: group
      A, 12 patients with development of acute or chronic NLH, and group B, 15 patients
      without development of hyperinflation. NLH was defined as radiologic mediastinal
      shift with flattening of the ipsilateral diaphragm associated with respiratory
      dysfunction or hemodynamic instability. All preoperative and postoperative data
      from recipients and data from donors were analyzed. RESULTS: There were no
      differences between the two groups regarding age, preoperative partial pressure
      of oxygen, partial pressure of carbon dioxide, acid-base status, donor lung size
      and physiological structure, side of transplantation, primary pathologic
      condition, rejection score, infection episodes and obliterative bronchiolitis in
      the transplanted lung after operation. Patients with NLH had a significantly
      higher preoperative mean pulmonary artery pressure of 31.6 mm Hg (confidence
      interval [CI] 26.7 to 35.7), transpulmonary gradient of 20.5 mm Hg (CI 17.4 to
      23.5), a lower mean forced expiratory volume in 1 second of 427 ml (CI 352 to
      502), and higher mean residual volume of 4450 ml (CI 3769 to 5132). The duration
      of ventilation, 168 hours (CI 45 to 290), and the postoperative mean pulmonary
      artery pressure of 26 mm Hg (CI 23 to 28.7) are significantly higher in the
      hyperinflation group. Early death in group A (n = 5) was higher than in group B
      (no deaths) (p = 0.02). Six patients in group A required surgical treatment (two
      early native lung volume reductions, two early ipsilateral retransplantations,
      and two late contralateral transplantations). Group A patients tended to have
      poorer long-term lung function after transplantation, with reduced forced
      expiratory volume in 1 second, forced vital capacity, and higher residual volume
      (p = NS). CONCLUSION: Patients with end-stage emphysema and relative pulmonary
      hypertension, severe airway obstruction, and air trapping are at greatest risk
      for development of early and late NLH. In this subgroup of patients, an
      alternative treatment strategy may be considered.

PMID- 9513859
TI  - Respiratory syncytial virus-associated infections in adult recipients of solid
      organ transplants.
AB  - BACKGROUND: Although respiratory syncytial virus (RSV) infection is known to
      cause severe pulmonary infections in bone marrow transplant recipients, less is
      known concerning its clinical course, diagnosis, and treatment in solid organ
      transplant recipients. METHODS: We have conducted a retrospective review of seven
      cases of RSV infection in adult recipients of solid organ transplants. Four
      patients received lungs, two received kidneys, and one received a heart. RESULTS:
      The most common presenting complaints were dyspnea (100%), cough (86%), and
      purulent sputum (57%). Physical findings included fever (43%), rales (100%), and
      wheezing (29%). Admission studies were significant for leukocytosis (29%), a left
      shift in the white blood cell differential (86%), and hypoxemia (mean PaO2 = 64).
      Chest radiographs were unchanged in 29% and showed infiltrates that were
      bilateral in 43% and unilateral in 29%. Pulmonary function tests in lung
      transplant recipients showed a mean fall in forced expiratory volume in 1 second
      of 26% and a fall in diffusion capacity for carbon monoxide of 24%. Five patients
      were treated with aerosolized ribavirin. Adverse events associated with treatment
      included wheezing (80%) and mild dyspnea (20%). The conditions of three of five
      treated patients were believed by their physicians to have improved 7 days after
      the initiation of therapy. One of the five treated patients died, and both
      untreated patients survived. CONCLUSIONS: RSV infection in this population has an
      extremely variable severity and clinical course, usually dominated by lower
      respiratory symptoms and obstructive airway disease. Ribavirin therapy is well
      tolerated, but its efficacy remains unknown.

PMID- 9513860
TI  - Recovery of sheep hearts after perfusion preservation or static storage with
      crystalloid media.
AB  - BACKGROUND: These experiments were designed to evaluate the viability of large
      hearts after preservation by use of procedures that have shown good results with
      small animal hearts. Efficacy of novel long-term preservation protocols should be
      documented with a large animal model before such procedures can be adopted for
      clinical use. We studied the recovery of sheep hearts that were perfusion
      preserved in media containing two different substrate mixtures and hearts stored
      without perfusion either in University of Wisconsin solution modified to maintain
      tissue adenosine triphosphate content or in Stanford solution. METHODS: Six
      groups of sheep hearts were studied: I, fresh nonpreserved controls; II, hearts
      perfusion-preserved at 11 degrees C for 24 hours by use of an oxygenated
      extracellular-type medium with pyruvate + glucose substrate; III, hearts
      preserved as for II but with aspartate + glutamate + glucose substrate; IV,
      hearts stored without perfusion at 3 degrees C for 24 hours in University of
      Wisconsin solution containing 2,3-butanedione monoxime 30 mmol/L, CaCl2 1 mmol/L,
      and fresh reduced glutathione 3 mmol/L; V, hearts stored without perfusion at 3
      degrees C for 4 hours in Stanford solution; VI, hearts preserved as for II but
      without perfusion. Recovery was measured for 6 hours in a Langendorff model,
      perfused with an erythrocyte + albumin medium. RESULTS: Hearts that were
      perfusion-preserved with both substrate mixtures and hearts stored in modified
      University of Wisconsin solution recovered function that was not significantly
      different from control subjects. Hearts stored in Stanford medium did not recover
      as well as did groups II, III, and IV. Left ventricular pressure and peak rate of
      left ventricular relaxation of the Stanford group were lower, and left
      ventricular enddiastolic pressure was higher, than those values for controls
      (repeated measures analysis of variance; Dunnett's procedure). The group VI
      hearts did not recover function at all. CONCLUSION: The results suggest that
      large hearts preserved with medium containing either aspartate + glutamate +
      glucose or pyruvate + glucose have comparable recovery after long-term perfusion
      preservation. Aspartate + glutamate may offer advantages for clinical use because
      of their lower production of lactate and better chemical stability compared with
      pyruvate. Static storage in modified University of Wisconsin solution also
      produced viable hearts with recovery comparable to perfusion-preserved aspartate
      + glutamate + glucose hearts. Tests of these preservation media and procedures
      with large transplanted hearts are warranted.

PMID- 9513861
TI  - New solution for prolonged myocardial preservation for transplantation.
AB  - BACKGROUND: A solution for prolonged cold storage of the heart has been
      developed. The Jerusalem-Cape Town Solution (JCT) is an "intracellular" type
      cardioplegic solution and is formulated to (1) minimize hypothermic-induced cell
      swelling, (2) diminish intracellular acidosis, (3) prevent the expansion of the
      interstitial space during the reperfusion, (4) protect against oxygen free
      radical injury during early reperfusion, and (5) provide substrates for
      regenerating high-energy phosphates. METHODS: With a Langendorff model, rat
      hearts were subjected to 15 minutes of perfusion with Krebs-Henseleit, 10 minutes
      of cardioplegic infusion and 20 hours of cold storage (5 degrees to 6 degrees C).
      Hearts were reperfused for 60 minutes and hemodynamic recovery was assessed. The
      hearts were assigned to three groups (eight hearts in each), according to the
      cardioplegic solution used: group 1, JCT; group 2, Bretschneider's HTK
      cardioplegic solution; and group 3 University of Wisconsin cold storage solution.
      RESULTS: After 60 minutes of reperfusion, the recovery of the coronary artery
      flow in group 1 (JCT) was significantly better than in group 2, and slightly
      better than in group 3 (64% +/- 8.9%, 47.2% +/- 11.6%, 52.5% +/- 19.9%, mean +/-
      SD, respectively; group 1 versus group 2, p < 0.01). The recovery of the left
      ventricular developed pressure (LVDP) was significantly better in group 1
      compared with group 2 and group 3 (60.2% +/- 14.5%, 41.1% +/- 12.6% and 36.5% +/-
      10.1%, respectively; p < 0.01). The recovery of the heart contractility expressed
      by the product of LVDP and the heart rate (LVDP x heart rate) was significantly
      higher in group 1 than in group 2 and group 3 (47.5% +/- 3.4%, 23.6% +/- 9.6%,
      and 28.7% +/- 8.3%, respectively, p < 0.001). In hearts stored for 12 hours in
      JCT or HTK, the recovery of the heart contractility did not differ significantly
      (73.4% +/- 12.7% or 70.8% +/- 30.8%, respectively). Modified reperfusion aimed to
      improve postischemic heart recovery did not bring significant changes in cardiac
      mechanical function but resulted in an increase in postischemic coronary artery
      flow recovery in hearts reperfused with amino acid-enriched buffer. CONCLUSIONS:
      The JCT solution is effective (as well as HTK) in preserving the ischemic hearts
      for up to 12 hours. It is superior to HTK or University of Wisconsin solution at
      20 hours of isolated ischemic storage.

PMID- 9513862
TI  - Cryptogenic organizing pneumonia is an important cause of graft dysfunction and
      should be included in the classification of pulmonary allograft rejection.

PMID- 9513863
TI  - Is there a role for measuring exhaled nitric oxide in lung transplant recipients
      with chronic rejection?

PMID- 9513864
TI  - Effects of a 2-hour run on metabolic economy and lower extremity strength in men
      and women.
AB  - Changes in running economy, or the oxygen cost of running at a given submaximal
      speed (ml/m/kg), during prolonged exercise have been well described in men but
      not in women. Lower extremity strength changes associated with prolonged exercise
      have never been addressed. We examined changes in running economy and strength
      following a 2-hour run in eight men and eight women. Knee and hip strength were
      measured pre- and post-running. Peak oxygen consumption (VO2peak) and oxygen
      consumption at ventilatory threshold were determined. Subjects then ran for 2
      hours at an intensity which elicited ventilatory threshold (68.7% vs. 66.6% of
      VO2peak for men and women, p = 0.5). Water was ingested at a rate of 0.5% of body
      weight each half hour. Oxygen uptake (VO2) and respiratory exchange ratio were
      measured initially and at 1 and 2 hours. Body weight declined in the men (p =
      0.001) but not in the women (p = 0.12). Running economy decreased in the men (p <
      0.001) but not in the women (p = 0.084). At 2 hours of running, knee flexion and
      extension strength declined significantly in the men only (effect of gender x
      time, p < 0.014), but hip flexion, abduction, and adduction strength declined in
      both genders. Decreased knee extensor/flexor strength was evident in men only,
      while decreased hip strength was independent of gender. We conclude that 2 hours
      of running produced changes in knee strength and running economy in men only.

PMID- 9513865
TI  - Comparison of five isometric exercises in the recruitment of the vastus medialis
      oblique in persons with and without patellofemoral pain syndrome.
AB  - Strengthening of the vastus medialis oblique (VMO) has been advocated as a
      treatment for patellofemoral pain syndrome (PFPS), as weakness of this component
      of the quadriceps is postulated to contribute to malalignment of the patella.
      This study investigated the surface electromyographic activity (EMG) of the VMO
      relative to the vastus lateralis (VL) during five isometric exercises in eight
      PFPS female subjects and 19 controls. The area under the EMG curve of each muscle
      was normalized to the EMG area acquired while subjects performed a submaximal
      isometric contraction (50% of maximum voluntary contraction), and the
      "normalized" outcome measure was expressed as a proportion (VMO:VL). A two-factor
      repeated measures analysis of variance indicated no differences in the VMO:VL
      proportion between the control group and PFPS participants across the five
      exercises (p > .05). The VMO:VL proportions for medial tibial rotation and knee
      extension combined and knee extension alone were significantly greater than for
      the other three exercises (p < 0.005). Hip adduction or the combination of hip
      adduction and knee extension did not result in greater recruitment of the VMO
      compared with the VL.

PMID- 9513866
TI  - Centralization of low back pain and perceived functional outcome.
AB  - McKenzie's methods for evaluating and treating low back pain are used often but
      studied little. When using the McKenzie system, it is important to observe signs
      of symptom movement to a central location (centralization). This study
      investigated the relationships between centralization of low back pain and/or
      radiculopathy and the subjects' rating of functional outcome. Thirty-six subjects
      with low back pain volunteered to participate and were evaluated and treated by
      six researchers. Subjects were tested initially and again 14 days after
      initiation of treatment using the Oswestry Low Back Pain Disability Questionnaire
      and the Performance Assessment and Capacity Testing Spinal Function Sort (SFS).
      Symptoms were monitored for the occurrence of "complete centralization." Of the
      36 subjects, 25 showed complete centralization within 14 days. The SFS score
      changes were significantly higher for subjects who completely centralized (p =
      0.015). The results supported the hypothesis that subjects who centralize will
      have improved functional outcome and, thus, quality of life. However, shorter
      time to occurrence of complete centralization does not necessarily correlate with
      improved outcome.

PMID- 9513867
TI  - Craniosacral rhythm: reliability and relationships with cardiac and respiratory
      rates.
AB  - Craniosacral rhythm (CSR) has long been the subject of debate, both over its
      existence and its use as a therapeutic tool in evaluation and treatment. Origins
      of this rhythm are unknown, and palpatory findings lack scientific support. The
      purpose of this study was to determine the intra- and inter-examiner
      reliabilities of the palpation of the rate of the CSR and the relationship
      between the rate of the CSR and the heart or respiratory rates of subjects and
      examiners. The rates of the CSR of 40 healthy adults were palpated twice by each
      of two examiners. The heart and respiratory rates of the examiners and the
      subjects were recorded while the rates of the subjects' CSR were palpated by the
      examiners. Intraclass correlation coefficients were calculated to determine the
      intra- and inter-examiner reliabilities of the palpation. Two multiple regression
      analyses, one for each examiner, were conducted to analyze the relationships
      between the rate of the CSR and the heart and respiratory rates of the subjects
      and the examiners. The intraexaminer reliability coefficients were 0.78 for
      examiner A and 0.83 for examiner B, and the interexaminer reliability coefficient
      was 0.22. The result of the multiple regression analysis for examiner A was R =
      0.46 and adjusted R2 = 0.12 (p = 0.078) and for examiner B was R = 0.63 and
      adjusted R2 = 0.32 (p = 0.001). The highest bivariate correlation was found
      between the CSR and the subject's heart rate (r = 0.30) for examiner A and
      between the CSR and the examiner's heart rate (r = 0.42) for examiner B. The
      results indicated that a single examiner may be able to palpate the rate of the
      CSR consistently, if that is what we truly measured. It is possible that the
      perception of CSR is illusory. The rate of the CSR palpated by two examiners is
      not consistent. The results of the regression analysis of one examiner offered no
      validation to those of the other. It appears that a subject's CSR is not related
      to the heart or respiratory rates of the subject or the examiner.

PMID- 9513868
TI  - Physical therapy and health-related outcomes for patients with common orthopaedic
      diagnoses.
AB  - Assessing both physical and mental health is necessary in clinical settings to
      quantify the scope of disability and to evaluate the effectiveness of treatment
      programs. Changes in health-related quality of life following physical therapy
      treatment for many patients with orthopaedic-related diagnoses is not known. The
      purposes of this study were to describe changes in health-related quality of life
      between the initial assessment and the time of discharge from physical therapy
      for the most common orthopaedic diagnoses and to compare the patterns of deficit
      among diagnostic categories. Patient outcomes in this study were evaluated from a
      large database generated by the Focus on Therapeutic Outcomes (FOTO) network.
      Health-related and employment outcomes were described for adult patients who were
      classified using ICD-9-CM codes. The most common orthopaedic diagnostic
      categories were sacroiliac sprain, back sprain, low back pain (radiating and
      nonradiating), neck sprain, neck pain (radiating and nonradiating), adhesive
      capsulitis of the shoulder, rotator cuff injury, shoulder sprain, knee
      dislocation, knee sprain, and knee derangement. The primary outcome measure was a
      17-item questionnaire (the MOS-17) derived from the RAND 36-Item Health Survey
      (SF-36) and the 12-item Short Form Health Survey (SF-12). The comparison of each
      cohort to population norms was made by calculating a standard score on patient
      data adjusted for age and gender. An effect size was calculated to measure the
      change in health or employment status between the initial assessment and
      discharge from physical therapy. For all diagnostic categories, health-related
      quality of life with respect to norms and employment status showed a consistent
      pattern of improvement at the time of discharge compared with the initial
      assessment. There were only small changes in physical function for neck and
      shoulder diagnostic categories. Nearly all of the diagnostic categories had large
      reductions in bodily pain. The amount of clinical change in the physical
      components of health-related quality of life--especially the physical function
      and role physical domains--differed substantially across specific diagnostic
      categories. The largest improvements in the physical function occurred for
      patients with knee dislocation and knee sprain. Patients with knee dislocation
      also had the largest improvement in role limitations due to physical problems.
      The design of this study does not permit conclusions about the efficacy of
      physical therapy. Further study is needed to determine if the finding of
      different levels of health status improvement across diagnostic categories was
      due to the nature of the outcome measure, the type of treatments given to each
      patient, or other confounding variables, like depression or preinjury functional
      level.

PMID- 9513870
TI  - Decelerated rehabilitation after ACL reconstruction revisited.

PMID- 9513869
TI  - Management of acute calcific tendinitis of the shoulder.
AB  - Calcific deposits located within the tendons of the rotator cuff are frequently
      seen in patients presenting with shoulder pain. The pathogenesis of calcific
      tendinitis and the optimum management of patients presenting with acute symptoms
      are unclear. This paper reviews the incidence, proposed etiologies, and a unique
      treatment approach of rotator cuff calcific tendinitis. A case report of a
      patient with acute calcific tendinitis and subsequent shoulder motion and
      strength deficits is presented. A rational evaluation and treatment plan is
      outlined, which includes management and posttreatment changes, and radiographic
      findings are discussed. A team-management approach by physical therapy and
      orthopaedics services is emphasized.

PMID- 9513871
TI  - c-myc, c-erbB-2, c-fms and bcl-2 oncoproteins. Expression in normal placenta,
      partial and complete mole, and choriocarcinoma.
AB  - OBJECTIVE: To determine the expression of bcl-2, c-myc, c-fms and c-erbB-2
      oncoproteins in normal placentas, partial and complete hydatidiform moles, and
      choriocarcinomas and to examine the possible presence of mutations in the K-ras
      gene in complete moles and choriocarcinomas. STUDY DESIGN: The expression of the
      above oncoproteins was determined immunohistochemically by specific antibodies
      for these proteins on formalin-fixed paraffin sections of 18 normal placentas, 17
      partial moles, 25 complete moles and 11 choriocarcinomas. This was followed by
      polymerase chain reaction analysis (exons 12 and 13) of K-ras gene for possible
      mutations in complete moles and choriocarcinomas. RESULTS: Expression of c-fms
      oncoprotein appeared confined to the cytoplasm of syncytiotrophoblastic cells.
      The c-fms protein staining intensity of the syncytiotrophoblastic layer showed no
      significant difference among the four gestational tissues. c-erbB-2 antibody
      expression was confined to the cellular membrane of the extravillous trophoblast.
      When compared with normal placenta or partial mole, the expression of c-erbB-2
      protein was significantly stronger in complete mole (P < .0001 and P < .0001,
      respectively) and choriocarcinoma (P < .0001 and P < .0001, respectively).
      Expression of bcl-2 protein was significantly stronger in the syncytiotrophoblast
      in complete mole and choriocarcinoma as compared to both normal placenta and
      partial mole (P < .0001 and P < .0001, respectively). Staining of c-myc of the
      syncytiotrophoblastic layer was significantly stronger in placenta, complete mole
      and choriocarcinoma than in partial mole (P < .0001, P < .0001 and P < .0001,
      respectively). Mutation in K-ras gene was not found in any of the 22 complete
      moles or 11 choriocarcinomas examined. CONCLUSION: Our data suggest that c-myc, c
      erbB-2, c-fms and bcl-2 oncoproteins may be important in the pathogenesis of
      complete mole and choriocarcinoma. However, while both complete mole and
      choriocarcinoma were characterized by overexpression of c-myc, c-erbB-2 and bcl
      2, partial mole generally did not strongly express these three oncoproteins.

PMID- 9513872
TI  - Management of resistant gestational trophoblastic tumors.
AB  - OBJECTIVE: To analyze the causes of therapeutic success and failure in the
      management of patients with high-risk gestational trophoblastic tumors (GTTs).
      STUDY DESIGN: Analysis of 272 consecutive high-risk patients treated at the
      trophoblastic disease center at the Charing Cross Hospital between 1979 and 1995.
      RESULTS: EMA (etoposide, methotrexate, actinomycin D)/CO (cyclophosphamide,
      vincristine) chemotherapy is our treatment of choice for patients with high-risk
      GTT. In 272 consecutive patients the cumulative five-year survival was 86.2% (95%
      confidence interval, 81.9-90.5%). No deaths occurred from GTT more than two years
      after the start of treatment. In patients whose disease became resistant to
      EMA/CO or relapsed after receiving EMA/CO, the majority (70%) could be salvaged
      with further chemotherapy (usually with the EP (etoposide, cisplatin)/EMA
      chemotherapy with or without surgery. Multivariate analysis identified the
      following adverse prognostic factors: presence of liver metastases (P < .0001),
      prolonged interval from antecedent pregnancy (P < .0001), presence of brain
      metastases (P = .0008) and term delivery of antecedent pregnancy (P = .045).
      Intensive chemotherapy for treating high-risk GTT carries a small risk of
      inducing second malignancies, and two patients developed acute myeloid leukemia,
      2 cervical malignancy and 1 gastric adenocarcinoma after receiving EMA/CO
      chemotherapy. CONCLUSION: EMA/CO is an effective and well-tolerated regimen for
      high-risk GTT. Salvage chemotherapy with EP/EMA is effective in the majority of
      patients whose disease is resistant to EMA/CO and should be combined with surgery
      when the dominant site of resistant disease is known. Major adverse prognostic
      variables have been identified, and patients with combinations of these factors
      should be considered for innovative therapeutic approaches from the outset.

PMID- 9513874
TI  - Umbilical cord prolapse. Is the time from diagnosis to delivery critical?
AB  - OBJECTIVE: To review the peripartum clinical course of patients whose pregnancies
      are complicated by umbilical cord prolapse at a large teaching hospital and to
      evaluate the time from diagnosis to delivery and its impact on neonatal outcome.
      STUDY DESIGN: The computerized perinatal database at Hartford Hospital was used
      to identify all cases of umbilical cord prolapse from 1988 to 1994. Each maternal
      and neonatal chart was reviewed, and the following variables were evaluated:
      gestational age, fetal presentation, status of membranes, time from diagnosis to
      delivery, mode of delivery, type of anesthesia and neonatal outcome. RESULTS: A
      total of 65 cases of umbilical cord prolapse were identified from 26,545
      deliveries. There were 48 cases of frank cord prolapse and 17 of occult prolapse.
      Cord prolapse occurred with artificial rupture of membranes in 51% of cases and
      in 74% of patients at term. There were 59 cesarean births and 6 vaginal
      deliveries (5 in the occult prolapse group). The mean time from diagnosis to
      delivery was 20 minutes (range, 2-77). None of the neonates with an occult cord
      prolapse had a five-minute Apgar score < 7, while 9 (19%) of the neonates with
      frank prolapse had a five-minute Apgar score < 7. In the frank prolapse group,
      there were five cases of neonatal asphyxia, all at a gestational age of > or = 36
      weeks, and all were delivered by cesarean section. The mean delivery time for
      these affected neonates was 11 minutes (range, 5-16). CONCLUSION: Our review
      indicated that umbilical cord prolapse continues to be associated with poor
      perinatal outcomes in some cases despite emergency delivery in a modern, high
      risk obstetric unit. The asphyxiated neonate had a shorter-than-average time from
      diagnosis to delivery, suggesting that the time from diagnosis to delivery may
      not be the only critical determinant of neonatal outcome, particularly with frank
      cord prolapse. Occult cord prolapse was associated with less perinatal morbidity
      when compared to frank prolapse.

PMID- 9513873
TI  - p53, p21, Rb and mdm2 oncoproteins. Expression in normal placenta, partial and
      complete mole, and choriocarcinoma.
AB  - OBJECTIVE: To determine the expression of p53, p21, Rb and mdm2 proteins in
      normal placentas, partial and complete hydatidiform moles, and choriocarcinomas
      and to examine possible p53 mutations in specimens from p53-positive cases. STUDY
      DESIGN: Expression of the above oncoproteins was determined immunohistochemically
      by specific antibodies for these proteins on formalin-fixed paraffin sections of
      18 normal placentas, 17 partial moles, 25 complete moles and 11 choriocarcinomas.
      This was followed by polymerase chain reaction single-strand conformation
      polymorphism (PCR-SSCP) analysis (exons 5, 6, 7, 8, 9, 10, 11) for possible p53
      mutation in specimens from p53-positive cases of complete mole and
      choriocarcinoma. RESULTS: p53 Oncoprotein immunoreactivity was significantly
      stronger in complete mole and choriocarcinoma than in normal placenta (P < .0001,
      P < .0001) and in partial mole (P < .0001, P < .0001). Positive staining for p21
      oncoprotein was also significantly stronger in complete mole (P < .0001, P <
      .0001) and in choriocarcinoma (P < .0001, P < .0001) than in placenta and partial
      mole. We found significantly stronger staining for Rb protein in complete mole (P
      < .03) and choriocarcinoma (P < .03) than in partial mole. Partial mole and
      complete mole expressed significantly stronger staining of mdm2 than placenta (P
      < .007, P < .07, respectively). We found only one nonsense mutation in p53 with
      PCR analysis; that strongly suggests that in complete mole and choriocarcinoma
      the overexpressed p53 protein was wild type. CONCLUSION: Altered expression of
      p53, p21, Rb and mdm2 may be important in the pathogenesis of both complete mole
      and choriocarcinoma. However, unlike complete molar pregnancy, partial mole is
      not characterized by overexpression of p53. Overexpression of p53 and mdm2
      proteins in complete mole and choriocarcinoma may be associated with more
      aggressive behavior in gestational trophoblastic disease.

PMID- 9513875
TI  - Iron in prenatal multivitamin/multimineral supplements. Bioavailability.
AB  - OBJECTIVE: To determine the effect of the differences in the content of essential
      and nonessential ingredients and of a standardized meal on iron bioavailability
      from four popular prenatal multivitamin/multimineral supplements. STUDY DESIGN:
      Iron absorption during an eight-hour period following ingestion of a
      multivitamin/multimineral formulation, both fasting and postprandial, after a
      standardized meal, was measured in five groups of 20 pregnant women (24-32 weeks
      of gestation) and statistically compared. The prenatal formulations were Natalins
      Rx, Prenatal 1/1, Stuartnatal Plus and Prenate 90. One-A-Day (without iron) was
      included in the study for the control group. RESULTS: The descending order of
      absorption, both fasting and postprandial, were Prenate 90, Stuartnatal Plus,
      Prenatal 1/1 and Natalins Rx. Total iron absorption for each formulation group
      during the postprandial phase was higher than during the fasting phase. However,
      the net amount of iron absorption (in both the fasting and postprandial phases)
      from three of the four formulations (Stuartnatal Plus, Prenatal 1/1 and Prenate
      90) provided the minimal 3.0 mg of supplemental iron per day recommended by the
      National Academy of Science. CONCLUSION: The observed differences in iron
      absorption between prenatal supplements apparently reflect the effects of the
      various combinations of vitamins, essential minerals and additives. The absolute
      amount of elemental iron contained in a prenatal multivitamin/ multimineral
      formulation does not ensure availability.

PMID- 9513876
TI  - The OB/GYN clerkship rotation sequence. Does it affect performance on final
      examinations?
AB  - OBJECTIVE: To determine if the timing of the obstetric/gynecologic (OB/GYN)
      clerkship affects the final grade achieved. STUDY DESIGN: The final examination
      grades on the OB/GYN clerkship for 165 students over a three-year period were
      compared according to when in the year the clerkship was taken. Premedical
      Medical College Admission Test scores (MCAT) were used to determine the academic
      potential of each clerkship group. RESULTS: There was a statistically significant
      correlation between the MCAT scores and the National Board of Medical Examiners
      clerkship examination score (r = .22, P < .005). No differences were found in the
      clerkship examination scores for students doing their rotations early or late in
      the third year. CONCLUSION: These results suggest that students with similar
      academic potential will do equally well on OB/GYN clerkship examinations whether
      they take their rotation early or late in the third year of medical school.

PMID- 9513877
TI  - Normal and gestational diabetic pregnancies. Lipids, lipoproteins and
      apolipoproteins.
AB  - OBJECTIVE: To evaluate plasma lipids, lipoproteins and apolipoprotein changes
      induced by gestational diabetes. STUDY DESIGN: In this case-control study, 60
      women between 26 and 32 weeks of pregnancy were allocated to four groups
      according to lipid status and glucose tolerance: (1) normolipemia and no
      gestational diabetes, (2) normolipemia and gestational diabetes, (3) hyperlipemia
      and no gestational diabetes, and (4) hyperlipemia and gestational diabetes. Total
      cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein
      cholesterol, very low density lipoprotein cholesterol (VLDLc), triglycerides,
      triglycerides/very low density lipoprotein (VLDL), apolipoproteins (APO) A1 and
      APO B, APO B-VLDL and APO B/low-density lipoprotein were measured. RESULTS: There
      were no statistically significant differences in the normolipemic group of women.
      Among the hyperlipemic patients, gestational diabetic women showed lower VLDLc
      when compared to nondiabetic patients. CONCLUSION: Our results, comparing groups
      separated groups by lipid status, show that the only difference in lipid profile
      associated with glucose intolerance is lower VLDLc in hyperlipemic patients.

PMID- 9513878
TI  - Fever of unknown origin in the puerperium. A case report.
AB  - BACKGROUND: Postpartum fever is a common problem for obstetricians, but fever of
      unknown origin (FUO) occurring in the puerperium may be relatively unfamiliar and
      a challenge to the majority of obstetricians. CASE: A 29-year-old woman had a FUO
      detected during the puerperium. Despite serial examinations and therapeutic
      trials, the fever persisted for three weeks without a clinical improvement or
      definite infection source. The presence of a huge uterine myoma was observed. The
      patient finally underwent myomectomy, and a pathology review revealed a cellular
      leiomyoma associated with massive infarction and acute inflammation. The fever
      subsided substantially on the third day postoperatively. CONCLUSION: Although a
      uterine leiomyoma as a cause of fever in the puerperium is not new, rarely does
      it cause prolonged fever. It should be taken into consideration in pregnant women
      known to have uterine myomas during pregnancy and in the puerperium, especially
      if FUO develops. Nonsteroidal antiinflammatory drugs can be a tool for making the
      differential diagnosis in such a patient, and exploratory laparotomy can be
      delayed until an emergency condition occurred, especially important during
      pregnancy.

PMID- 9513879
TI  - Managing extreme uterine torsion at term. A case report.
AB  - BACKGROUND: Extreme uterine torsion at term is a rare obstetric event and raises
      several critical management considerations. CASE: At the time of repeat cesarean
      section at term for fetal malpresentation, 180 degrees torsion of the uterine
      corpus was diagnosed. At laparotomy, the gravid uterus would not yield to
      anatomic repositioning, necessitating delivery through a deliberate posterior
      transverse hysterotomy. No maternal abdominopelvic pathology or fetal
      abnormalities were demonstrated. Prophylactic bilateral shortening of the round
      ligaments was performed at delivery to prevent recurrent torsion in the immediate
      puerperium. The patient recovered uneventfully. CONCLUSION: Deliberate posterior
      cesarean hysterotomy is an option for fetal delivery with irreducible torsion,
      and round ligament plication may prevent recurrent torsion in the immediate
      puerperium.

PMID- 9513880
TI  - Rudimentary horn pregnancy.

PMID- 9513881
TI  - New laparoscopic technique for interstitial pregnancy resection.

PMID- 9513882
TI  - Laparoscopy for adnexal torsion in pregnant women.

PMID- 9513883
TI  - Cesarean section for suspected fetal distress.

PMID- 9513884
TI  - What is your diagnosis? Multiple portosystemic shunts, acquired or congenital.

PMID- 9513885
TI  - Medical management of congenital portosystemic shunts in 27 dogs--a retrospective
      study.
AB  - Case records of 27 dogs with medically managed congenital portosystemic shunts
      were reviewed. Fourteen were followed up by telephone questionnaires to the
      owners. Age, breed, sex, clinical signs and blood results were similar to
      previous studies. Weight and quality of life were stable or improved on treatment
      in all cases. Total serum protein concentration and alanine aminotransferase and
      alkaline phosphatase activities fell significantly during treatment. Fourteen
      dogs were euthanased, four were lost to follow-up and nine remained alive. Mean
      survival time for the dogs euthanased was 9.9 months. Mean follow-up period for
      the dogs still alive was 56.9 months and all had survived more than 36 months
      from diagnosis. Surviving dogs with intrahepatic shunts had a significantly
      shorter follow-up period than dogs with extrahepatic shunts. Two prognostic
      indicators were identified, age at initial signs and blood urea concentration on
      presentation, both correlating with survival time. It was demonstrated that a
      significant proportion of dogs with portosystemic shunts managed medically have a
      good prognosis.

PMID- 9513886
TI  - Urethral sphincter mechanism incompetence in the male dog: importance of bladder
      neck position, proximal urethral length and castration.
AB  - The radiographs of 37 incontinent adult male dogs with urethral sphincter
      mechanism incompetence were compared with those of 28 control dogs to determine
      if, as in the bitch, differences in bladder neck position and urethral length
      were implicated in the pathophysiology of urethral sphincter mechanism
      incompetence. Bladder neck position was significantly different; compared with
      continent dogs, incontinent animals were significantly more likely (P < 0.005) to
      have intrapelvic than intra-abdominal bladder necks. However, after allowing for
      the influence of body size, and unlike the situation in the bitch, there was no
      significant difference in proximal urethral length between the two groups.
      Bladder neck position was significantly related to prostate size (P < 0.001) and
      it is suggested that this is one reason why castrated male dogs are more prone to
      urethral sphincter mechanism incompetence than entire animals. A logistic
      regression analysis revealed that both bladder neck position and castration
      status were significant risk factors for incontinence and that they appeared to
      be acting independently of each other.

PMID- 9513887
TI  - Evaluation of brush cytology in the diagnosis of chronic intranasal disease in
      cats.
AB  - Brush cytology was used as a diagnostic aid in 85 cats affected with chronic
      intranasal disease. Fifty-three of these cases, sampled over a five-year period,
      were included in this study, while the other cases were excluded due to poor
      cellularity of the cytological samples (nine cases) or a lack of histological or
      follow-up data (23 cases). Thirty-six brush samples were classified by cytology
      as inflammatory. Subsequent histological examination revealed a false negative
      diagnosis of neoplasia in six cats, two of which had malignant tumours (one
      adenocarcinoma and one lymphoma), the remaining four having benign tumours (two
      adenomas and two osteochondromas). Seventeen samples were classified by brush
      cytology as neoplastic. This was confirmed in 16 of these cases by histology or
      follow-up (nine epithelial malignant tumours, six lymphomas and one
      osteosarcoma). In the remaining case, a false positive diagnosis of lymphoma was
      made. The procedure had an overall 86.8 per cent (46/53) agreement between the
      diagnosis of inflammatory conditions versus neoplasia, with a sensitivity of 72.7
      per cent, a specificity of 96.8 per cent, a predictive value of a positive test
      of 94.1 per cent and a predictive value of a negative test of 83.3 per cent.

PMID- 9513888
TI  - Feline chronic renal failure: clinical findings in 80 cases diagnosed between
      1992 and 1995.
AB  - Clinical and laboratory findings at the time of first diagnosis in 80 cats with
      chronic renal failure (CRF) were examined in a prospective study to determine the
      survival time of these animals and identify possible factors contributing to the
      progression of feline CRF. On the basis of clinical presentation, animals were
      assigned to one of three groups; compensated (n = 15), uraemic (n = 39) and end
      stage (n = 26) CRF. Loss of renal concentrating ability was a common finding,
      even before clinical signs of renal disease were evident. The plasma creatinine
      concentration at initial presentation was a poor predictor of survival time and
      the presence of significant anaemia was indicative of a poor prognosis. The study
      demonstrated the highly variable degree of renal impairment present at the time
      of diagnosis and the potentially long survival time of many compensated and
      uraemic cases.

PMID- 9513889
TI  - Ectopic Psoroptes cuniculi infestation in a pet rabbit.
AB  - A case of Psoroptes cuniculi infestation of the ears and body of a pet rabbit,
      with severe lesions on the skin of the caudoventral abdomen, is reported.
      Treatment with ivermectin injection followed by fipronil application appeared to
      be safe and was successful in eliminating infection.

PMID- 9513890
TI  - Tail tip necrosis in two litters of Birman kittens.
AB  - The development of tail tip necrosis in two litters of Birman kittens from the
      same queen is described. On the basis of blood group testing of the queen and one
      of the stud cats, a presumptive diagnosis of neonatal isoerythrolysis involving
      cold-acting agglutinins was made. It is suggested that on presentation of tail
      tip necrosis in kittens a diagnosis of neonatal isoerythrolysis or
      isoagglutination should be considered.

PMID- 9513891
TI  - Hypocortisolaemia in a Labrador retriever.
AB  - A four-year-old Labrador retriever was presented with lethargy and exercise
      intolerance. Clinical examination was unremarkable. A subnormal cortisol response
      to adrenocorticotrophin hormone (ACTH) was demonstrated (plasma cortisol
      concentrations before and after administration of ACTH were both below the
      detection limit of the assay) but plasma aldosterone concentrations were within
      the normal range. Endogenous plasma ACTH concentrations were high, indicating
      primary adrenocortical disease. Following glucocorticoid supplementation at a
      replacement dose (prednisolone 0.1 mg/kg) the dog made a full clinical recovery.

PMID- 9513892
TI  - Comparison of haematological analyses of blood taken from the cephalic and
      marginal ear veins in cats.
AB  - Various haematological components were compared in blood samples from the
      cephalic and marginal ear vein of 21 cats. Test results tended to be higher in
      blood samples from the cephalic vein, although significant differences were only
      detected for haemoglobin concentration, white blood cell count and the absolute
      numbers of neutrophilic granulocytes and lymphocytes. Differences in test results
      between the two veins were small and apparently of only minor practical
      importance, thereby further substantiating the suitability of the marginal ear
      vein nick technique as a means of obtaining small blood samples from cats.

PMID- 9513893
TI  - Reciprocal translocation in a case of canine basal cell carcinoma.
AB  - A case of basal cell carcinoma in a 10-year-old spaniel dog was analysed
      cytogenetically. A reciprocal translocation t(10;35) was detectable.

PMID- 9513894
TI  - Campylobacter infection.

PMID- 9513895
TI  - Catecholamines modulate podocyte function.
AB  - The aim of this study was to investigate the influence of adrenoceptor agonists
      on the intracellular calcium activity ([Ca2+]i), membrane voltage (Vm), and ion
      conductances (Gm) in differentiated mouse podocytes. [Ca2+]i was measured by the
      Fura-2 fluorescence method in single podocytes. Noradrenaline and the alpha 1
      adrenoceptor agonist phenylephrine induced a reversible and concentration
      dependent biphasic increase of [Ca2+]i in podocytes (EC50 approximately 0.1
      microM for peak and plateau), whereas the alpha 2-adrenoceptor agonist UK 14.304
      did not influence [Ca2+]i. The [Ca2+]i response induced by noradrenaline was
      completely inhibited by the alpha 1-adrenoceptor antagonist prazosin (10 nM). In
      a solution with a high extracellular K+ (72.5 mM), [Ca2+]i was unchanged and the
      [Ca2+]i increase induced by noradrenaline was not inhibited by the L-type Ca2+
      channel blocker nicardipine (1 microM). Vm and Gm were examined with the patch
      clamp technique in the slow whole-cell configuration. Isoproterenol,
      phenylephrine, and noradrenaline depolarized podocytes and increased Gm. The
      order of potency for the adrenoceptor agonists was isoproterenol (EC50
      approximately 1 nM) > noradrenaline (EC50 approximately 0.3 microM) >
      phenylephrine (EC50 approximately 0.5 microM). The beta 2-adrenoceptor antagonist
      ICI 118.551 (5 to 100 nM) inhibited the effect of isoproterenol on Vm.
      Stimulation of adenylate cyclase by forskolin mimicked the effect of
      isoproterenol on Vm and Gm (EC50 approximately 40 nM). Isoproterenol induced a
      time- and concentration-dependent increase of cAMP in podocytes. The effect of
      isoproterenol was unchanged in the absence of Na+ or in an extracellular solution
      with a reduced Ca2+ concentration, whereas it was significantly increased in an
      extracellular solution with a reduced Cl- concentration (from 145 to 32 mM). The
      data indicate that adrenoceptor agonists regulate podocyte function: They
      increase [Ca2+]i via an alpha 1-adrenoceptor and induce a depolarization via a
      beta 2-adrenoceptor. The depolarization is probably due to an opening of a cAMP
      dependent Cl- conductance.

PMID- 9513896
TI  - Cortical and medullary hemodynamics in deoxycorticosterone acetate-salt
      hypertensive mice.
AB  - The effect of acutely increasing renal perfusion pressure or extracellular fluid
      volume on renal medullary and cortical blood flow was examined in the low-renin
      deoxycorticosterone acetate (DOCA)-salt hypertension model in mice. A 50-mg DOCA
      tablet was implanted, and 1% saline was given as drinking water for 3 wk.
      Medullary and cortical blood flow were determined with laser-Doppler flowmetry,
      and whole-kidney blood flow was measured with a transit-time ultrasound flowprobe
      around the renal artery. In control mice, total renal blood flow ranged from 6.3
      and 7.6 ml/min per g kidney weight and in DOCA-salt mice from 4.3 and 4.7 ml/min
      per g kidney weight, respectively, and was minimally affected as renal perfusion
      pressure was increased. Renal vascular resistance increased correspondingly.
      During stepwise increases in renal artery pressure from 90 to 140 mmHg, medullary
      blood flow progressively increased in control mice to 125% of baseline values,
      whereas cortical blood flow did not change. In DOCA-salt mice, increasing BP from
      100 to 154 mmHg had no effect on either cortical or medullary blood flow. Urine
      flow and sodium excretion were lower in DOCA-salt mice than in controls and
      increased nearly to the same extent in both groups after volume expansion with
      isotonic saline. Total renal blood flow increased after saline loading, more in
      controls than in DOCA-salt mice. Increases in medullary blood flow after saline
      loading were up to 122% of baseline values in controls and demonstrated a
      significantly steeper slope than the 110% of baseline increases in DOCA-salt
      mice. Cortical blood flow, however, was not different between the groups. Thus,
      medullary blood flow is not as tightly autoregulated as cortical blood flow in
      normal mice. Natriuresis with acute volume loading is facilitated by increased
      medullary blood flow. In DOCA-salt mice, the medullary blood flow reaction to
      renal perfusion pressure increases is abolished, whereas flow increases with
      extracellular volume expansion are diminished. These results suggest that
      diminished pressure-natriuresis responses in DOCA-salt mice are related to
      perturbed medullary blood flow.

PMID- 9513898
TI  - Genetic differences define severity of renal damage after L-NAME-induced
      hypertension in rats.
AB  - Genetic factors are important in determining the susceptibility to renal damage.
      In a backcross of the hypertensive and proteinuric fawn-hooded Erasmus University
      Rotterdam (FHH/EUR) rat with the normotensive, nonproteinuric August Copenhagen
      Irish (ACI/EUR) rat, two genes (denoted Rf-1 and Rf-2) were genetically mapped
      for parameters of functional and structural renal damage. The aim of the present
      study was to investigate the susceptibility to functional and structural renal
      damage in heterozygous (FHH X ACI) F1 rats compared with the parental FHH and ACI
      strains at similar levels of systolic BP (SBP). BP elevation was induced by
      chronic treatment with NG-nitro-L-arginine methyl ester (L-NAME) in either a low
      dose (LD, 75 to 100 mg/L) or a high dose (HD, 175 to 250 mg/L) in the drinking
      fluid. Survival of FHH rats and, to a lesser extent, F1 rats, was adversely
      affected by L-NAME treatment. All ACI rats except for one ACI-HD animal survived.
      In all strains, L-NAME caused a dose-dependent increase in SBP. At similar levels
      of SBP, the increase in functional renal damage, as indicated by the level of
      albuminuria, was higher in F1 compared with ACI, but lower compared with FHH. The
      same differences were found for the level of structural renal damage, as
      indicated by the incidence of glomerulosclerosis. Both the SBP and the average BP
      burden (SBP-Av), defined as SBP averaged over the period of follow-up, directly
      correlated with the level of albuminuria and incidence of glomerulosclerosis in
      all strains. However, the increase in the degree of renal damage per mmHg
      increase in SBP or SBP-Av was significantly higher in the F1 rats compared with
      ACI, but lower compared with FHH rats. Values for these F1 rats were closer to
      the ACI rats than to values for the FHH rats and increased above an SBP level of
      180 mmHg. The F1 rats, being heterozygous for Rf-1 and Rf-2, as well as for other
      potential genes responsible for renal disease, were largely, but not completely,
      protected from hypertension-induced renal damage. It is concluded that complete
      susceptibility to hypertension-associated renal damage in rats primarily depends
      on the presence of predisposing genes for renal failure even after a significant
      increase in BP.

PMID- 9513897
TI  - Dietary salt loading decreases the expressions of neuronal-type nitric oxide
      synthase and renin in the juxtaglomerular apparatus of angiotensinogen gene
      knockout mice.
AB  - The present study investigates whether neuronal type nitric oxide synthase (N
      NOS) in the macula densa participates in the regulation of renal renin expression
      during altered dietary salt intake in angiotensinogen gene-knockout (Atg-/-)
      mice. Wild-type (Atg+/+) and Atg+/+ mice were fed a low-salt (0.04% NaCl), normal
      salt (0.3% NaCl), or high-salt (4% NaCl) diet for 2 wk. Histochemical staining
      for NADPH diaphorase (NADPHd) and renin were analyzed morphometrically. Levels of
      N-NOS and renin mRNA in renal cortical tissues were determined by reverse
      transcription-PCR and Northern blot analysis, respectively. In animals fed a
      normal-salt diet, the renal expressions of N-NOS and renin were markedly
      increased in Atg-/- mice compared with Atg+/+ mice. When mutant mice were fed a
      high-salt diet, the signal intensity of the NADPHd reaction and the number of
      positively stained macula densa cells were significantly decreased. The levels of
      renal cortical N-NOS mRNA were also suppressed by the treatment. These changes
      were paralleled by decreases in renal renin-immunoreactive areas and the levels
      of renin mRNA. On the other hand, salt restriction did not produce further
      significant increases in the renal N-NOS and renin expressions in mutant mice,
      whereas a parallel inverse relationship was observed between these enzyme
      expressions and the levels of salt intake in wild-type mice. These results
      suggest that the N-NOS expression in the macula densa is inversely regulated by
      salt intake and that the enzyme activity is functionally linked to renal renin
      production. Salt-modulated renal N-NOS and renin expressions are independent on
      angiotensin formation in Atg-/- mice.

PMID- 9513899
TI  - Activation of glomerular mitogen-activated protein kinases in angiotensin II
      mediated hypertension.
AB  - The in vivo signal transduction pathway, responsible for hypertension-induced
      glomerular injury, remains to be clarified. In this study, the effect of
      angiotensin II (Ang II)-induced hypertension was examined on glomerular mitogen
      activated protein kinases (MAPK), including extracellular signal-regulated kinase
      (ERK) and c-jun NH2-terminal kinase (JNK), and on glomerular transcription
      factors activator protein-1 (AP-1) and Sp 1. MAPK activities were determined by
      in-gel kinase assay. DNA binding activity of AP-1 and Sp 1 was determined by gel
      mobility shift assay. Continuous infusion of Ang II (1000 ng/kg per min,
      intravenously) to conscious rats rapidly increased BP, followed by the rapid and
      transient activation of glomerular p42 and p44 ERK and p46 and p55 JNK with the
      peak at 15 to 180 min. Glomerular AP-1 binding activity was increased 2.6-fold (P
      < 0.01) at 24 h after the start of Ang II infusion. Supershift analysis showed
      that the activated AP-1 complexes contained c-Fos and c-Jun proteins. On the
      other hand, glomerular Sp 1 DNA binding activity was not changed throughout 7 d
      of Ang II infusion. These results provided the first in vivo evidence that Ang II
      induced hypertension causes the activation of glomerular ERK and JNK, leading to
      the activation of AP-1. Thus, ERK and JNK signaling cascades, via the activation
      of AP-1, may be implicated in the development of hypertension-induced glomerular
      injury.

PMID- 9513900
TI  - Development of vascular pole-associated glomerulosclerosis in the Fawn-hooded
      rat.
AB  - Fawn-hooded hypertensive (FHH) rats constitute a spontaneous model of chronic
      renal failure with early systemic and glomerular hypertension, proteinuria, and
      development of focal and segmental glomerulosclerosis. The goal of the present
      study was to elucidate a step-by-step sequence of histopathologic events leading
      from an initial glomerular injury to segmental sclerosis. Segmental sclerosis in
      the FHH rat is consistently associated with the glomerular vascular pole. The
      initial injury involves the expansion of primary branches of the afferent
      arteriole. Apposition of those capillaries to Bowman's capsule, together with the
      degeneration and detachment of corresponding podocytes, allows parietal cells to
      attach to the naked glomerular basement membrane of this capillary, i.e., allows
      the formation of a tuft adhesion to Bowman's capsule. The adhesion enlarges to a
      broad synechia by encroaching to neighboring capillaries, apparently based on
      progressive podocyte degeneration at the flanks of the adhesion. Capillaries
      inside the adhesion--before undergoing collapse or hyalinization--appear to stay
      perfused for some time and to maintain some kind of filtration misdirected toward
      the cortical interstitium. Thereby, a prominent paraglomerular space comes into
      existence, enlarging in parallel with the adhesion. Toward the cortical
      interstitium this space is delimited by a layer of sheetlike fibroblast
      processes, which has obviously been assembled in response to the formation of
      this space. Toward the urinary space, the paraglomerular space is demarcated by
      the parietal epithelium and by the interface between the adhesion and the
      "intact" tuft remnant. Thus, the sclerotic tuft portions all become enclosed
      within the paraglomerular space.

PMID- 9513901
TI  - Inhibition of matrix metalloproteinases attenuates anti-Thy1.1 nephritis.
AB  - There is accumulating evidence that matrix metallo-proteinases (MMP) play a
      prominent role in glomerular inflammatory diseases. The aim of the present study
      was to determine the anti-inflammatory effects of the synthetic MMP inhibitor BB
      1101 in acute anti-Thy1.1 nephritis. Sixty-three male Wistar rats were studied:
      healthy rats (n = 9), treated healthy rats (n = 9), nephritic rats (n = 18), and
      treated nephritic rats (n = 27). BB-1101 therapy (30 mg/kg body wt per d) of
      nephritic animals was initiated either 2 d before (n = 18) or 2 d after (n = 9)
      disease induction. Renal histology was analyzed 11 d after induction of the
      nephritis, at the peak of MMP-2 production and total glomerular cellularity.
      Pretreatment of nephritic rats by BB-1101 resulted in a significant amelioration
      of glomerular histology, assessed by glomerular cellularity, extracellular matrix
      deposition, and size of glomerular cross-sections. These beneficial effects were
      less pronounced, but in part still significant, in animals treated by BB-1101
      after induction of anti-Thy1.1 nephritis. Proteinuria, expressed as area under
      the curve of the protein:creatinine ratio versus time, was clearly decreased in
      both groups of treated nephritic rats. Healthy control rats were not affected by
      MMP inhibitor treatment. In summary, the present study demonstrates for the first
      time in vivo that mesangial cell proliferation can be effectively suppressed by
      MMP inhibition. Thus, MMP inhibition by synthetic compounds may represent a new
      approach to the therapy of mesangial cell-mediated forms of glomerulonephritis.

PMID- 9513902
TI  - Expression and localization of cyclooxygenase isoforms and cytosolic
      phospholipase A2 in anti-Thy-1 glomerulonephritis.
AB  - Glomerular expression of the major rate-limiting enzymes for prostanoid
      synthesis, cyclooxygenase isoforms (COX-1 and COX-2) and cytosolic phospholipase
      A2 (cPLA2), was investigated in anti-Thy-1 nephritis in rats. Ribonuclease
      protection assay demonstrated minimal COX-1 mRNA expression in glomeruli of
      control rat kidneys and a gradual increase of expression from day 1 to day 10
      after administration of monoclonal anti-rat Thy-1 antibody. On the other hand,
      COX-2 mRNA expression, also minimal in the normal glomeruli, was enhanced in a
      biphasic pattern with two peaks at 1 h and day 10. Expression of cPLA2 mRNA,
      which was undetectable in normal glomeruli, was induced on day 1 and increased
      gradually in a pattern similar to that of COX-1 mRNA expression.
      Immunofluorescence microscopy, using antibodies against COX isoforms, showed that
      both COX-1 and COX-2 were negligible or faintly detectable in the glomeruli of
      control rat kidneys. In contrast, the immunofluorescence for COX-1 was
      intensified on days 4 and 10 along the glomerular capillary walls probably in
      glomerular epithelial and/or endothelial cells, whereas COX-2 staining was
      exclusively enhanced in the glomerular epithelial cells at 1 h and day 10 during
      the course of anti-Thy-1 nephritis. These findings indicate that prostanoids
      generated through induction of COX-1, COX-2, and cPLA2 are implicated in the
      mediation of the mesangial cell injury model. In particular, the upregulation of
      COX-2 expression in glomerular epithelial cells in the selective mesangial cell
      injury model suggests an intercellular interaction between mesangial cells, and
      glomerular epithelial cells.

PMID- 9513903
TI  - Rat mesangial cells express macrophage migration inhibitory factor in vitro and
      in vivo.
AB  - Mesangial cells are thought to promote glomerular macrophage accumulation in
      glomerulonephritis. This may occur through the production of macrophage migration
      inhibitory factor (MIF), a molecule known to regulate macrophage accumulation at
      sites of inflammation. To study this, glomerular MIF expression and macrophage
      accumulation were examined in rat anti-Thy-1 disease, a model of
      mesangioproliferative nephritis. In situ hybridization and immunohistochemistry
      showed that MIF is expressed by some podocytes in normal rat glomeruli. De novo
      MIF expression by glomerular endothelium was seen on day 1 of anti-Thy-1 disease.
      On day 6, glomerular MIF mRNA and protein expression were prominent in segmental
      proliferative lesions, which was also the location of most infiltrating
      macrophages. Double-staining identified de novo MIF mRNA and protein expression
      by proliferating mesangial cells within these lesions. Cytokine regulation of
      mesangial cell MIF expression was examined in vitro. Northern blotting showed
      that cultured rat mesangial cells express a single 0.6-kb species of MIF mRNA,
      and Western blotting detected a single protein band of 12.5 kD. Six-hour
      stimulation of mesangial cells with interferon-gamma or platelet-derived growth
      factor significantly increased MIF mRNA levels. However, the addition of
      recombinant MIF to mesangial cells did not affect mesangial cell proliferation or
      constitutive transforming growth factor-beta mRNA expression, nor did MIF induce
      monocyte chemoattractant protein-1 mRNA expression. In conclusion, this is the
      first study to demonstrate that mesangial cells can produce MIF in vivo and in
      vitro. It is postulated that mesangial cell MIF production in response to injury
      acts to promote macrophage accumulation within segmental proliferative lesions in
      rat anti-Thy-1 nephritis.

PMID- 9513904
TI  - The 1 alpha-hydroxylase locus is not linked to calcium stone formation or
      calciuric phenotypes in French-Canadian families.
AB  - Calcium urolithiasis is often associated with increased intestinal absorption and
      urine excretion of calcium, and has been suggested to result from increased
      vitamin D production. The role of the enzyme 1 alpha-hydroxylase, the rate
      limiting step in active vitamin D production, was evaluated in 36 families,
      including 28 sibships with at least a pair of affected sibs, using qualitative
      and quantitative trait linkage analyses. Sibs with a verified calcium
      urolithiasis passage (n = 117) had higher 24-h calciuria (P = 0.03), oxaluria (P
      = 0.02), fasting and postcalcium loading urine calcium/creatinine (Ca/cr) ratios
      (P = 0.008 and P = 0.002, respectively), and serum 1,25(OH)2 vitamin D levels (P
      = 0.02) compared with nonstone-forming sibs (n = 120). Markers from a 9
      centiMorgan interval encompassing the VDD1 locus on chromosome 12q13-14 (putative
      1 alpha-hydroxylase) were analyzed in 28 sibships (146 sib pairs) of single and
      recurrent stone formers and in 14 sibships (65 sib pairs) with recurrent-only (>
      or = 3 episodes) stone-forming sibs. Two-point and multipoint analyses did not
      reveal excess in alleles shared among affected sibs at the VDD1 locus. Linkage of
      stone formation to the VDD1 locus could be excluded, respectively, with a lambda
      d of 2.0 (single and recurrent stone formers) and 3.25 (recurrent stone formers).
      Quantitative trait analyses revealed no evidence for linkage to 24-h calciuria
      and oxaluria, serum 1,25(OH)2 vitamin D levels, and Ca/cr ratios. This study
      shows absence of linkage of the putative 1 alpha-hydroxylase locus to calcium
      stone formation or to quantitative traits associated with idiopathic
      hypercalciuria. In addition, there is coaggregation of calciuric and oxaluric
      phenotypes with stone formation.

PMID- 9513905
TI  - TNF-alpha increases albumin permeability of isolated rat glomeruli through the
      generation of superoxide.
AB  - Tumor necrosis factor-alpha (TNF-alpha) is a cytokine that plays a central role
      in inflammation. Glomerular levels of TNF-alpha are elevated in human and
      experimental glomerulonephritis. Glomerular cells produce and respond to TNF
      alpha. One of the mechanisms by which these cells respond to TNF-alpha is through
      generation of reactive oxygen species. In this study, the effect of TNF-alpha on
      albumin permeability (P(albumin)) of isolated rat glomeruli and the possible
      mechanism of this effect were examined. Isolated rat glomeruli were incubated
      with TNF-alpha (0.4 ng/ml), TNF-alpha with anti-TNF-alpha antibodies, and TNF
      alpha with the reactive oxygen species scavengers superoxide dismutase, catalase,
      DMSO, or dimethylthiourea for 12 min at 37 degrees C, and P(albumin) was
      calculated. TNF-alpha increased P(albumin) of isolated glomeruli compared with
      control (0.70 +/- 0.02, n = 25 versus 0.00 +/- 0.05, n = 26), and this effect was
      abrogated by anti-TNF-alpha antibodies (-0.18 +/- 0.05, n = 23). Superoxide
      dismutase abolished the increase in P(albumin) (-0.04 +/- 0.11, n = 23), whereas
      catalase (0.73 +/- 0.08, n = 30), DMSO (0.64 +/- 0.03, n = 10), or
      dimethylthiourea (0.51 +/- 0.08, n = 10) did not alter the effect of TNF-alpha.
      These results indicate that TNF-alpha increased P(albumin+)++ of isolated
      glomeruli and that the mediator of the increased P(albumin) is superoxide. It is
      concluded that TNF-alpha derived from glomerular or extraglomerular sources can
      increase glomerular P(albumin) through generation of superoxide and may lead to
      proteinuria.

PMID- 9513906
TI  - Mechanisms contributing to muscle-wasting in acute uremia: activation of amino
      acid catabolism.
AB  - Acute uremia (ARF) causes metabolic defects in glucose and protein metabolism
      that contribute to muscle wasting. To examine whether there are also defects in
      the metabolism of essential amino acids in ARF, we measured the activity of the
      rate-limiting enzyme for branched-chain amino acid catabolism, branched-chain
      ketoacid dehydrogenase (BCKAD), in rat muscles. Because chronic acidosis
      activates muscle BCKAD, we also evaluated the influence of acidosis by studying
      ARF rats given either NaCl (ARF-NaCl) or NaHCO3 (ARF-HCO3) to prevent acidosis,
      and sham-operated, control rats given NaHCO3. ARF-NaCl rats became progressively
      acidemic (serum [HCO3] = 21.3 +/- 0.7 mM within 18 h and 14.7 +/- 0.8 mM after 44
      h; mean +/- SEM), but this was corrected with NaHCO3. Plasma valine was low in
      ARF-NaCl and ARF-HCO3 rats. Plasma isoleucine, but not leucine, was low in ARF
      NaCl rats, and isoleucine tended to be lower in ARF-HCO3 rats. Basal BCKAD
      activity (a measure of active BCKAD in muscle) was increased more than 17-fold (P
      < 0.01) in ARF-NaCl rat muscles, and this response was partially suppressed by
      NaHCO3. Maximal BCKAD activity (an estimate of BCKAD content), subunit mRNA
      levels, and BCKAD protein content were not different in ARF and control rat
      muscles. Thus, ARF increases branched-chain amino acid catabolism by activating
      BCKAD by a mechanism that includes acidosis. Moreover, in a muscle-wasting
      condition such as ARF, there is a coordinated increase in protein and essential
      amino acid catabolism.

PMID- 9513907
TI  - A randomized study comparing methylprednisolone plus chlorambucil versus
      methylprednisolone plus cyclophosphamide in idiopathic membranous nephropathy.
AB  - To assess whether chlorambucil or cyclophosphamide may have a better therapeutic
      index in patients with idiopathic membranous nephropathy, we compared two
      regimens based on a 6-mo treatment, alternating every other month
      methylprednisolone with chlorambucil or methylprednisolone with cyclophosphamide.
      Patients with biopsy-proven membranous nephropathy and with a nephrotic syndrome
      were randomized to be given methylprednisolone (1 g intravenously for 3
      consecutive days followed by oral methylprednisolone, 0.4 mg/kg per d for 27 d)
      alternated every other month either with chlorambucil (0.2 mg/kg per d for 30 d)
      or cyclophosphamide (2.5 mg/kg per d for 30 d). The whole treatment lasted 6 mo;
      3 mo with corticosteroids and 3 mo with one cytotoxic drug. Among 87 patients
      followed for at least 1 yr, 36 of 44 (82%; 95% confidence interval [CI], 67.3 to
      91.8%) assigned to methylprednisolone and chlorambucil entered complete or
      partial remission of the nephrotic syndrome, versus 40 of 43 (93%; 95% CI, 80.9
      to 98.5%) assigned to methylprednisolone and cyclophosphamide (P = 0.116). Of
      patients who attained remission of the nephrotic syndrome, 11 of 36 in the
      chlorambucil group (30.5%) and 10 of 40 in the cyclophosphamide group (25%) had a
      relapse of the nephrotic syndrome between 6 and 30 mo. The reciprocal of plasma
      creatinine improved in the cohort groups followed for 1 yr for both treatment
      groups (P < 0.01) and remained unchanged when compared with basal values in the
      cohort groups followed for 2 and 3 yr. Six patients in the chlorambucil group and
      two in the cyclophosphamide group did not complete the treatment because of side
      effects. Four patients in the chlorambucil group but none in the cyclophosphamide
      group suffered from herpes zoster. One patient per group developed cancer. It is
      concluded that in nephrotic patients with idiopathic membranous nephropathy both
      treatments may be effective in favoring remission and in preserving renal
      function for at least 3 yr.

PMID- 9513908
TI  - Isolation of modified ubiquitin as a neutrophil chemotaxis inhibitor from uremic
      patients.
AB  - Uremic toxins are factors that accumulate in the serum and peritoneal cavity of
      uremic patients. They are responsible for a variety of functional disturbances
      and also contribute to the increased risk of infection by interfering with
      essential functions of the unspecific immune response. From the peritoneal
      effluent of peritoneal dialysis (PD) patients, a peptide was isolated by applying
      three different chromatographic methods. This peptide inhibits the chemotactic
      movement of polymorphonuclear leukocytes (PMNL) in an in vitro assay in a
      concentration-dependent, nonreversible manner, and therefore belongs to the group
      of uremic toxins. Amino acid sequencing showed that the isolated peptide has the
      same amino terminal sequence as ubiquitin. The peptide also reacted with anti
      ubiquitin antibodies in a Western blot experiment, but had a more acidic
      isoelectric point than ubiquitin. By using affinity chromatography, anti
      ubiquitin antibody binding fractions were isolated from all PD and hemodialysis
      (HD) patients investigated. These fractions contained the same acidic band and
      also significantly inhibited PMNL chemotaxis. Ubiquitin per se had no effect on
      PMNL chemotaxis. Therefore, it is concluded that from PD and HD patients a
      modified form of ubiquitin was isolated, and this modification was responsible
      for its inhibitory effect.

PMID- 9513909
TI  - Nature and biological significance of free radicals generated during bicarbonate
      hemodialysis.
AB  - This study investigates evidence of oxidative stress during bicarbonate
      hemodialysis by measuring total glutathione and lipid peroxidation products in
      plasma, and characterizes the free radicals produced by neutrophils from healthy
      volunteers when incubated in vitro with increasing concentrations of bicarbonate.
      Blood samples were taken from nine hemodialysis patients before and after two
      hemodialysis sessions. Plasma hydroperoxides and total glutathione were measured.
      A significant increase was found in total glutathione (1.04 +/- 0.4 versus 2.11
      +/- 0.9 microM, P < 0.001) and hydroperoxides by ferrous oxidation in xylenol
      orange version 2 method (4.6 +/- 0.53 versus 6.4 +/- 0.63 microM, P < 0.001)
      after hemodialysis, which indicated increased oxidative injury during
      hemodialysis. Normal neutrophils, activated by contact adhesion, produced a dose
      dependent increase in free radical production (measured by luminol-enhanced
      chemiluminescence) when incubated with increasing concentrations of bicarbonate
      (up to 35 mM). Bicarbonate had the same effect on the chemiluminescence of a cell
      free hypoxanthine/acetaldehyde system generating superoxide, but not on a glucose
      oxidase/myeloperoxidase system generating hydrogen peroxide and hypochlorous
      acid. These findings are consistent with (1) the hypothesis that superoxide
      generated during hemodialysis reacts with bicarbonate to form the toxic carbonate
      and formate radicals and (2) our previous observation that some patients
      undergoing bicarbonate (but not lactate) dialysis have increased plasma
      concentrations of formate after hemodialysis. It is suggested that the increased
      plasma total glutathione and hydroperoxide concentrations are a result of lipid
      peroxidation by these species. These reactive radicals can initiate lipid
      peroxidation and contribute to the cardiovascular complications of hemodialysis
      patients.

PMID- 9513910
TI  - Effect of formaldehyde/bleach reprocessing on in vivo performances of high
      efficiency cellulose and high-flux polysulfone dialyzers.
AB  - Among the several disadvantages of reprocessed dialyzers is the concern that
      reuse could decrease the clearance of uremic toxins, leading to a decrease in the
      delivered dose of dialysis. To examine this possibility in the clinical setting,
      the clearances of small molecular weight solutes (urea and creatinine) and middle
      molecular weight substances (beta 2 microglobulin) were compared during dialysis
      with "high-efficiency" cellulose (T220L) and "high-flux" polysulfone (F80B)
      dialyzers reprocessed with formaldehyde and bleach. In a crossover study, six
      chronic hemodialysis patients were alternately assigned to undergo 21 dialysis
      treatments with a single T220L dialyzer or F80B dialyzer. Each patient was
      studied during first use (0 reuse), 2nd reuse (3rd use), and 5th, 10th, 15th, and
      20th reuse of each dialyzer. Urea, creatinine, and beta 2 microglobulin
      clearances were measured at blood flow rates of 300 ml/min (Qb 300) and 400
      ml/min (Qb 400). Total albumin loss into the dialysate was measured during each
      treatment. Urea or creatinine clearance of new T220L dialyzers was not
      significantly different from that of new F80B dialyzers at either Qb. Urea
      clearance of F80B dialyzers at Qb 300 decreased from 241 +/- 2 ml/min for new
      dialyzers to 221 +/- 5 ml/min after 20 reuses (P < 0.001), and Qb 400 from 280 +/
      4 ml/min for new dialyzers to 253 +/- 7 ml/min after 20 reuses (P = 0.001).
      Similarly, with reuse, creatinine clearance of F80B dialyzers also decreased at
      Qb 300 (P = 0.07) and Qb 400 (P = 0.03). In contrast, urea or creatinine
      clearance of T220L dialyzers did not decrease with reuse at either Qb. Urea
      clearance of T220L dialyzers was significantly higher than that of F80B at Qb 300
      at the 5th, 10th, 15th, and 20th reuse (P < 0.001, = 0.005, = 0.004, and = 0.006,
      respectively), and Qb 400 at the 2nd, 5th, 10th, 15th, and 20th reuse (P = 0.04,
      0.008, 0.03, 0.02, and 0.008, respectively). Beta 2 microglobulin clearance of
      T220L dialyzers was < 5.0 ml/min across the reuses studied. Beta 2 microglobulin
      clearance of F80B was < 5.0 ml/min for new dialyzers, but increased to 21.2 +/-
      5.3 ml/min (Qb 300) and 23.6 +/- 3.3 ml/min (Qb 400) after 20 reuses (P < 0.001).
      Throughout the study, albumin was undetectable in the dialysate with T220L
      dialyzers. With F80B dialyzers, albumin was detected in the dialysate in four
      instances (total loss during dialysis, 483 mg to 1.467 g). In summary, the
      results of this study emphasize the greater need for information on dialyzer
      clearances during clinical dialysis, especially with reprocessed dialyzers. A
      more accurate knowledge of dialyzer performance in vivo would help to ensure that
      the dose of dialysis prescribed is indeed delivered to the patients.

PMID- 9513911
TI  - Pretransplantation hemodialysis strategy influences early renal graft function.
AB  - The influence of the pretransplantation hemodialysis strategy on early renal
      graft function was evaluated in 44 patients receiving hemodialysis in the 24 h
      preceding kidney transplantation and in 13 patients receiving hemodialysis more
      than 24 h before transplantation. The patients dialyzed less than 24 h before
      transplantation were stratified according to treatment with or without complement
      activating dialyzers (cuprophane, bioincompatible membrane [BICM] versus
      polysulfone, biocompatible membrane [BCM]) and with or without ultrafiltration
      (UF). Serum creatinine (Scr) at days 0, 2, 5, 10, and 30, the time for Scr to
      decrease 50% (T1/2Scr), the incidence of acute renal failure (ARF; defined as
      urinary volume < 500 ml/d and/or necessity for posttransplantation hemodialysis),
      and early graft dysfunction (defined as T1/2Scr > 3.5 d) were registered. Scr was
      higher in BCM- versus BICM-treated patients (P < 0.0001 by variance analysis) and
      in patients receiving UF versus those receiving no UF (P = 0.0009). T1/2Scr was
      higher in treatment with BICM versus BCM (7.4 +/- 7.9 versus 3.1 +/- 2.9 d; P <
      0.05) and UF versus no UF (7.1 +/- 7.7 versus 2.7 +/- 2.0 d; P < 0.01). The
      evolution of Scr was markedly more favorable in the patient group treated with
      BCM without UF (T1/2Scr 1.7 +/- 0.8 d) compared with the group treated with BICM
      and UF (T1/2Scr 9.3 +/- 9.1 d; P < 0.01). The remaining groups (BICM without UF
      and BCM with UF) showed intermediate results. The incidence of ARF and early
      graft dysfunction was higher in the group on BICM with UF compared to BCM without
      UF. Functional differences persisted up to 1 mo after transplantation. Patients
      who underwent dialysis with UF more than 24 h before transplantation had a more
      beneficial evolution of renal function parameters than those who were dialyzed
      with UF less than 24 h before transplantation. In conclusion, the use of BICM and
      the application of UF within 24 h before kidney transplantation enhance the risk
      of posttransplantation ARF and early graft dysfunction.

PMID- 9513912
TI  - Identification of clinical and histopathologic risk factors for diminished renal
      function 2 years posttransplant.
AB  - The aim of this study was to identify early clinical and pathologic variates that
      independently predict diminished renal allograft function at 24 mo
      posttransplant. A clinical pathologic data base was prospectively derived from 71
      patients in whom protocol renal biopsies were performed at 1, 2, 3, 6, and 12 mo
      posttransplant. The major end point was the 24-mo serum creatinine. Variates
      correlating independently (r2 = 0.67) with the 24-mo serum creatinine were the
      chronic biopsy scores (months 3 and 6), late rejections (months 4 to 6),
      cyclosporin A (CsA) levels (months 1 to 2), and delayed graft function. The
      adjusted odds ratio (OR) and 95% confidence interval (CI) for having a serum
      creatinine > or = 130 mumol/L at 24 mo increased for every year the donor age
      increased (OR = 1.07; 95% CI, 1.02 to 1.13; range, 9 to 55) or for each late
      rejection episode (OR = 5.9; 95% CI, 1.7 to 20.1), whereas a mean CsA level > 300
      micrograms/L from months 1 to 3 was protective (OR = 0.07; 95% CI, 0.01 to 0.43).
      Variates correlating independently (r2 = 0.53) with the change in serum
      creatinine from 6 to 24 mo (delta Cr6-24) were the chronic biopsy scores at
      months 3 and 6. The adjusted OR of the delta Cr6-24 rising > or = +20 mumol/L
      increased for every year the donor age increased (OR = 1.09; 95% CI, 1.02 to
      1.16; range 9 to 56) or when the 6-mo chronic biopsy score was > or = 2 (OR =
      6.6; 95% CI, 1.2 to 36.4). An estimate of the relative risk for diminished renal
      function at 2 yr can be assigned within 6 mo of transplant based on chronic
      pathology, late acute rejections, CsA levels, and donor age.

PMID- 9513913
TI  - Atherogenic lipoproteins stimulate mesangial cell p42 mitogen-activated protein
      kinase.
AB  - Previously, it has been shown that atherogenic lipoproteins, through the
      activation of glomerular cells, stimulate pathobiological processes involved in
      monocyte infiltration into the mesangium. This study examined the role of LDL and
      its oxidatively modified variants (mildly oxidatively modified LDL [mm-LDL] and
      oxidatively modified LDL [ox-LDL]) on the activation of mesangial cell p42
      mitogen-activated protein kinase (MAP kinase), a key intracellular signaling
      mechanism associated with cell proliferation. The incubation of mesangial cells
      with either LDL, mm-LDL, or ox-LDL induced the activation of MAP kinase dose
      dependently. The activation of MAP kinase by these lipoproteins in mesangial
      cells occurred biphasically: initially at 15 min of incubation period and at
      later time points of 8 to 24 h. No activation of MAP kinase was noted between 30
      min (except in LDL) and 6 h. The induction of MAP kinase by both mm-LDL and ox
      LDL was greater by 1.5- to 2-fold when compared with LDL. Similarly, these
      atherogenic lipoproteins stimulated mesangial cell proliferation.
      Lysophosphatidylcholine, a component of both oxidatively modified variants of
      LDL, markedly stimulated mesangial cell MAP kinase activity at early incubation
      times (5 to 30 min) but not at later time points (3 to 24 h), suggesting that
      lysophosphatidylcholine may, at least in part but not solely, act as an active
      component of ox-LDL-mediated effects. These data define putative key signal
      transduction events associated with lipoprotein-mediated induction of mesangial
      cell proliferation.

PMID- 9513914
TI  - Gender, degree of obesity, and discrepancy between urea and creatinine clearance
      in peritoneal dialysis.
AB  - The effect of gender and degree of obesity on the size indicators V, used to
      normalize urea clearance (Kt/Vur), and body surface area (BSA), used to normalize
      creatinine clearance (Ccr), in peritoneal dialysis was studied by: (1)
      mathematical comparison of the formulae used to estimate V (Watson and Hume) with
      the Dubois formula used to estimate BSA in peritoneal dialysis; and (2)
      comparison of percent deviation of BSA (delta BSA%) and V (delta V%) from ideal
      weight estimates in 933 clearance studies performed in actual patients (555 in
      men and 378 in women on continuous ambulatory peritoneal dialysis). V was
      estimated by the Watson formulae and BSA by the Dubois formula in these studies.
      delta BSA% and delta V% were stratified in 10% increments in deviation of body
      weight from ideal (delta W%) in these studies. Mathematically, the relationship
      between V and BSA is not linear. In the same subject, as obesity develops (delta
      W% increases) and BSA increases in a linear manner, V increases exponentially. In
      addition, there are substantial differences in the relationship between V and BSA
      caused by gender. For the same height and BSA, men have a larger V than women. In
      the clearance studies performed in actual continuous ambulatory peritoneal
      dialysis patients, the difference between delta V% and delta BSA% increased
      significantly (P < 0.0001) from the wasted to the obese subjects by one-way ANOVA
      in both men and women. Normalization of urea and creatinine clearances by
      different size indicators creates two types of mathematical distortion in the
      relationship between the two clearances. One distortion is caused by the degree
      of obesity. The second distortion is caused by gender. Use of the same size
      indicator to normalize both urea and creatinine clearances would eliminate these
      distortions.

PMID- 9513915
TI  - Acute interstitial nephritis.

PMID- 9513916
TI  - Hyperplasia of the juxtaglomerular complex with hyperaldosteronism and
      hypokalemic alkalosis. A new syndrome. 1962.
AB  - A new syndrome, characterized by hypertrophy and hyperplasia of the
      juxtaglomerular apparatus of the kidneys, aldosteronism resulting from adrenal
      cortical hyperplasia, and persistently normal blood pressure is described in two
      patients. Overproduction of aldosterone could not be prevented by sodium loading
      or by administration of albumin intravenously; it was associated with hypokalemic
      alkalosis and Pitressin-resistant impairment of urinary concentrating ability. In
      both subjects, increased amounts of circulating angiotensin were demonstrated;
      infusion of angiotensin II produced rises of blood pressure in both subjects
      considerably less than the rises induced by comparable doses in normal subjects.
      The sequence of events, (1) primary resistance to the pressor action of
      angiotensin, (2) compensatory overproduction of renin and thus of angiotensin,
      and (3) stimulation of adrenal cortex by angiotensin is consistent with all the
      information available about the syndrome.

PMID- 9513917
TI  - Impact of protein malnutrition on subcellular nucleic acid and protein status of
      brain of aluminum-exposed rats.
AB  - Nucleic acid and protein content in various cellular fractions of different
      regions of the brain were investigated in male albino rats following aluminum
      (Al) exposure (at the dose of 15% of LD50 i.p. for 28 days) on either an adequate
      or inadequate protein diet. It was observed that there was a decrease in
      homogenate DNA content in the thalamic area (Th), midbrain-hippocampal region
      (MH) and cerebellum (CL), but not in the cerebrum (CC) of the protein-restricted
      group of animals. Increased RNA content was recorded in the ribosomal and soluble
      fractions of CL of the adequately protein-fed animals compared to pair-fed
      controls. In the low-protein-fed animals, on the other hand, a decrease in RNA
      content was observed in the whole homogenate and nuclear fractions of CC, MH and
      CL, the ribosomal and soluble fractions of MH and CL, and in the mitochondrial
      fraction of TH. Ribonucleolytic activity was found to be increased only in the Th
      and CL of the adequately protein-fed group. Protein contents in the subcellular
      fractions of these four regions remain almost unaltered with the present dose and
      duration of Al-exposure; only the soluble fraction of CC and microsomal fraction
      of Th of the low-protein-fed group showed a significant decrease. The results of
      the present investigation confirm that Al has generally depressive effects on the
      nucleic acid metabolism of the brain and suggest that these effects are region
      specific as well as dependent on dietary protein level. It is further suggested
      that alterations in the cellular microenvironment, caused by protein
      malnutrition, may play a significant role in the modification of the effects of
      Al in the brain.

PMID- 9513918
TI  - Flow cytometric analysis for sperm viability and counts in rats treated with
      trimethylphosphate or pyridoxine.
AB  - Six-week old SD-Slc male rats were treated for 4 weeks with compounds known to
      induce toxicological changes in male reproductive organs (pyridoxine in saline,
      500 mg/kg/day, i.p.) or sperm (trimethylphosphate in distilled water, 100
      mg/kg/day, p.o.). Each sperm sample taken from the cauda epididymis was analyzed
      with flow cytometry for the evaluation of sperm viability and counts. Sperm
      motility and morphology by microscopical observation, and histopathological
      examination of reproductive organs were also performed for estimating the adverse
      effects of each compound on spermatogenesis and sperm. While a decrease in sperm
      motility was noted for the trimethylphosphate group, the low motile sperm was
      evaluated as being viable sperm, not moribund, with flow cytometry. In the
      pyridoxine group, microscopical observation revealed morphological changes of
      sperm and a decrease of motility. The present sperm analysis with flow cytometry
      also suggested morphological changes reflected by dot plot as well as decrease of
      sperm viability and counts. These results indicated that this procedure led to
      profound findings in the compound-treated animals, with evaluation as viable
      sperm, not moribund, in a low motile sperm sample, and suggesting morphological
      changes in the dot plot of flow cytometry.

PMID- 9513919
TI  - Pharmacokinetics and neurotoxicity of dipterex in hens. A comparative study of
      administration methods.
AB  - We compared the tissue concentration of dipterex and the inhibition of the
      neuropathy target esterase (NTE) activity among groups of hens (n = 8 each) which
      were intravenously (i.v.), subcutaneously (s.c.) or orally (p.o.) administered
      the insecticide dipterex. The tissue concentrations of dipterex in the s.c. group
      were higher than those in the i.v. and p.o. groups. When dosed subcutaneously,
      the tissue concentration of dipterex was high in the brain, spinal cord and
      muscle at 3 hr after dosing and then concentrated in the spinal cord and muscle
      for the subsequent 3 hr. When dosed intravenously or orally, dipterex was evenly
      dispersed in various tissues. All hens treated with dipterex showed acute
      neurotoxic signs within 15 min after dosing. The hens dosed intravenously
      recovered from this acute poisoning within 3 hr, and the hens dosed orally
      recovered within 6 hr, while the hens dosed subcutaneously recovered within 24 hr
      after dosing. One hen in the s.c. group exhibited acute neurological sequelae
      following the acute poisoning. In addition, the loss of body weight was the
      largest in the s.c. group (157 +/- 49 g), moderate in the i.v. group (133 +/- 91
      g), small in the p.o. group (96 +/- 54 g) and the smallest in the PMSF
      (phenylmethanesulfonyl fluoride, which was dosed to promote delayed neuropathy)
      group (80 +/- 49 g). In the untreated hens, the activity of NTE in both the
      cerebrum and cerebellum was higher than that in the midbrain (p < 0.01). There
      was no difference in NTE activity between the cerebrum and cerebellum. In both
      the cerebrum and midbrain, the inhibition of NTE activity in the p.o. group was
      less than that in the i.v. and s.c. groups, and no difference was found between
      the i.v. and s.c. groups. In the cerebellum, the inhibition of NTE activity in
      the s.c. group was larger than that in the i.v. and p.o. groups. These results
      indicate that the s.c. dosing of dipterex results in a stronger neurotoxicity
      compared to i.v. and p.o. dosing. However, it was difficult to induce the
      clinical signs of delayed neuropathy with any administration of dipterex in hens,
      even when the promotion of delayed neurotoxicity of dipterex was attempted with
      PMSF or double doses of dipterex itself.

PMID- 9513920
TI  - Induction of Leydig cell tumors by lacidipine via up-regulation of the LHRH
      receptor on Leydig cells in rats.
AB  - Long-term (78 weeks) administration of lacidipine, a dihydropyridine calcium
      antagonist, increased the incidence of Leydig cell tumors (LCTs) in Sprague
      Dawley rats. Lacidipine also increased and decreased the plasma luteinizing
      hormone (LH) and testosterone levels, respectively. Leydig cells from lacidipine
      treated rats showed increases in luteinizing hormone-releasing hormone (LHRH)
      receptor expression, protein kinase C (PKC) activity, expression of proto
      oncogenes, and 5-bromodeoxyridine uptake; whereas their calcium level, LH
      receptors, and testosterone content decreased. These data suggest that LHRH
      receptors play an important role in the development of rat LCTs induced by
      lacidipine, which activates a cascade of cell cycle-regulatory genes via PKC.
      When isolated Leydig cells were cultured with lacidipine or nicardipine, these
      changes in rat Leydig cells were not demonstrable in mice and monkeys, species
      having many fewer testicular LHRH receptors than rats. Thus, lacidipine may
      pharmacologically induce LCTs in rats but not in mice, with the difference
      depending on the presence or absence of testicular LHRH receptors. The induction
      of LCTs by lacidipine in rats is unlikely to occur in humans, since their Leydig
      cells lack LHRH receptors.

PMID- 9513922
TI  - Histopathological and immunohistochemical studies on experimental asthmatic model
      induced by aerosolized ovalbumin inhalation in guinea pigs.
AB  - To establish an animal model of asthma, fully sensitized guinea pigs inhaled
      aerosolized ovalbumin after booster treatments. At 0, 1, 3, 6, 24 and 48 hr after
      provocation (hap), histopathological and immunohistochemical changes in the
      airways of guinea pigs were examined. From 1 to 6 hap, anaphylactic changes such
      as perivascular edema and bronchoconstriction were detected. After that,
      intensive infiltration of eosinophils appeared and lasted until 48 hap. Temporal
      increases in the number of apoptotic cells and proliferating cell nuclear antigen
      positive cells were detected in the alveoli after the provocation. These findings
      suggest that this animal model showing both immediate and late asthmatic
      responses may be useful as an asthmatic model.

PMID- 9513921
TI  - Toxicity study of a rubber antioxidant, 2-mercaptobenzimidazole, by repeated oral
      administration to rats.
AB  - The chemical structure of 2-mercaptobenzimidazole (2-MBI), which is widely used
      as a rubber antioxidant, is partially similar to those of thiourea (TU) and
      ethylenethiourea (ETU), both potent thyrotoxic compounds. In order to determine
      the oral toxicity of 2-MBI, a 28-day repeated dose toxicity study in Wistar rats
      followed by observation over a 14-day recovery period was conducted at dose
      levels of 2, 10 and 50 mg/kg 2-MBI administered by gavage. No toxic deaths
      occurred due to 2-MBI treatment. Decreases of body weight gain and food
      consumption in the 50 mg/kg dose group were observed during the second half of
      the treatment period. In addition, hematological examination and serum
      biochemical tests revealed decreased white blood cells and hemoglobin and
      increased serum urea nitrogen, cholesterol, phospholipid, gamma-glutamyl
      transpeptidase and the Na+/K+ ratio in the 50 mg/kg dose group. Marked thyroid
      enlargement (to 10 fold the control weight), histopathologically associated with
      diffuse hyperplasia of follicles with decreased colloid and thickening of the
      fibrous capsule, was found. Reduction in thymus weight was also observed in a
      dose-dependent manner, without significant histopathological alteration. The non
      observed effect level (NOEL) of 2-MBI in this gavage study was found to be less
      than 2 mg/kg/day based on the significant decrease in thymus weight in the 2
      mg/kg 2-MBI treatment group. In an ancillary study, measurement of serum levels
      of T3, T4 and TSH, and thyroid weight after gavage treatment with 0.15 and 0.3
      mmol/kg of three antithyroid compounds for 14 days revealed a more potent
      antithyroid effect for 2-MBI than for TU or ETU.

PMID- 9513923
TI  - Effects of pH and osmolality on phlebitic potential of infusion solutions for
      peripheral parenteral nutrition.
AB  - In this study, we investigated the phlebitic potentials of several infusion
      solutions for peripheral parenteral nutrition to clarify the effects of pH and
      osmolality on the development of infusion phlebitis. A 10% glucose solution with
      electrolytes (GE, pH 4.93, 727 mOsm/kg), a 10% amino acid solution (AA, pH 6.95,
      929 mOsm/kg), or a 5:2 admixture of GE and AA (GEAA, pH 6.46, 779 mOsm/kg) was
      infused into the rabbit ear vein for 6 hr at 10 mL/kg/hr, and the infused veins
      were examined histopathologically. Both GE and AA caused phlebitic changes, such
      as loss of venous endothelial cells, inflammatory cell infiltration, and
      perivascular edema. However, their admixture, GEAA, caused scant phlebitic
      changes. These results were as follows: 1) rabbit peripheral veins could tolerate
      the pH (6.46) and the osmolality (779 mOsm/kg) of GEAA under the conditions of
      this study; 2) GE caused phlebitis due to its acidity (pH 4.93); 3) AA caused
      phlebitis due to its hyperosmolality (929 mOsm/kg); and 4) mixing GE and AA
      eliminated the factors causing phlebitis in each solution. The admixture of GE
      and another 10% amino acid solution (AB, pH 6.04) at the ratio of 5:2 (GEAB, pH
      5.76, 758 mOsm/kg) caused phlebitic changes. Since its osmolality was lower than
      that of GEAA, it was considered that GEAB caused phlebitic changes due to its
      acidity (pH 5.76), which was attributed to the acidic amino acid solution used as
      a component.

PMID- 9513924
TI  - Sex differences in immune responses to cephalothin in guinea pigs.
AB  - Guinea pigs of two strains, outbred Hartley and inbred Strain 2, were immunized
      subcutaneously with cephalothin (CET, 20 mg/body) alone, without adjuvant. Immune
      responses to the antibiotic were assessed by guinea-pig passive cutaneous
      anaphylaxis (GP-PCA) and active systemic anaphylaxis (GP-ASA) reactions. The
      immune response to CET in the female Hartley guinea pigs was higher than that in
      the males. In contrast, no difference in response to CET in Strain 2 guinea pigs
      was observed between males and females. These results suggested that female
      Hartley guinea pigs possessing a higher response should be employed in
      antigenicity studies involving the beta-lactam antibiotics.

PMID- 9513925
TI  - Comparative experimental study of Mg lactate, vitamin B6 and their association on
      the permeability of a human membrane. 1. Effect on the total ionic transfer
      through isolated amniotic membrane.
AB  - The effects of Mg lactate, vitamin B6 and their association were studied on the
      ionic transfer through a membranous model: the human isolated amniotic membrane.
      The ionic transfer was evaluated by measuring of the total conductance in the
      maternal to fetal way (GtM) and in the fetal to maternal way (GtF) and of the
      ionic fluxes (F1 on the maternal side, F2 on the fetal side) and of the ratio
      F1/F2. Whatever the concentration, Mg lactate decreased GtM, F1, F2, F1/F2 but
      had a concentration-dependent effect on GtF. Vitamin B6 had no significant effect
      on GtF, F1, F2, F1/F2, but decreased GtM whatever its concentration. The
      association Mg lactate + vitamin B6 presented a biphasic action on GtM, GtF, F1,
      F2 and F1/F2: decrease at low ratio and increase from ratio equal to 8. This
      association induced interesting effect in the case of therapeutic use in
      comparison with the effects of separated compounds.

PMID- 9513926
TI  - Magnesium modulates ouabain action on angiotensin II-induced aldosterone
      synthesis in vitro.
AB  - Ouabain can block the action of angiotensin II (AII on aldosterone secretion in
      both rat and human adrenal tissue although its action is much more potent on
      human zona glomerulosa cells (ZG). Since magnesium can antagonize digitalis
      action in vivo, we have examined the interaction of both agents on aldosterone
      secretion in both rat and human adrenal cells. Ouabain itself at high
      concentration (10(-5) M) in Mg++ buffer blocks AII action on aldosterone
      secretion on rat ZG cells and at 1000-fold lower concentrations inhibits AII
      action in human cells as previously reported by us. When buffer Mg++ is higher
      (4mM) than normal (0.7 mM) in cultured human adrenal cells it decreases both
      basal aldosterone secretion (8.6 +/- 0.4 vs. 6.8 +/- 0.2, p < 0.001) and AII
      action on aldosterone (13.9 +/- 0.6 vs. 9.7 +/- 0.7 ng/10(6) cells/h, p < 0.01).
      High Mg++ buffer had this effect at both 10(-8) and 10(-7) M concentrations of
      ouabain (control 8.6 +/- 0.4, AII [10(-9) M] 13.9 +/- 0.7, AII + Ouabain [5 x 10(
      8) M] 10.9 +/- 0.6, AII + ouabain [10(-7) M] 7.8 +/- 0.3 ng/10(6) cells/h, both p
      < 0.01 vs. AII). In contrast, a low Mg++ buffer stimulated both basal (6.9 +/-
      0.2 vs. 8.3 +/- 0.4 ng/10(6) cells/h, p < 0.01) and AII stimulation of
      aldosterone secretion (8.4 +/- 0.2 vs. 9.8 +/- 0.4 ng/10(6) cells/h, p < 0.01).
      When ouabain was added to low Mg++ buffer there was further inhibition of AII
      induced aldosterone secretion than with normal Mg++ buffer. However, the effect
      of ACTH on aldosterone was not altered by changes in Mg++. We conclude that
      ouabain actions and the effect of angiotensin II on aldosterone is inhibited by
      an increased level of Mg++ while low levels of Mg++ are stimulatory to both basal
      and AII action on aldosterone.

PMID- 9513927
TI  - Fractional excretion of magnesium in normal subjects and in patients with
      hypomagnesemia.
AB  - The aim of our study was the determination of fractional excretion of magnesium
      (FEMg++) in both normal subjects and hypomagnesemic patients. 142 subjects aged
      26-72 years, recruited from our lipid clinic (control population) and 74
      hypomagnesemic patients, aged 36-75 years, were studied. The mean FEMg++ in the
      control population was 1.8 per cent (range, 0.5-4 per cent). FEMg++ was not
      correlated with either serum magnesium or with serum creatinine. The mean FEMg++
      in patients with hypomagnesemia of extrarenal origin was 1.4 per cent (range, 0.5
      2.7 per cent), while the mean FEMg++ in hypomagnesemic patients in whom renal
      magnesium loss was the main etiologic factor for the pathogenesis of
      hypomagnesemia was 15 per cent (range, 4-48 per cent). In both groups of
      hypomagnesemic patients FEMg++ was positively correlated with the urinary
      magnesium to creatinine molar ratio, but was not correlated with serum magnesium
      or creatinine levels. FEMg++ could better distinguish the two groups of
      hypomagnesemic patients than the urinary magnesium to creatinine molar ratio.
      Hypomagnesemic patients exhibited a cluster of other acid-base and electrolyte
      abnormalities, mainly respiratory alkalosis, hypokalemia, hypophosphatemia, and
      hypocalcemia. In conclusion, in hypomagnesemic patients with normal renal
      function FEMg++ is a very useful tool for the diagnostic approach of
      hypomagnesemia. A value more than 4 per cent is indicative of inappropriate
      magnesium loss.

PMID- 9513928
TI  - Dietary magnesium intake in a French adult population.
AB  - Magnesium intake was assessed using six 24-h dietary records during a 1-year
      period in 5,448 subjects (3,111 women 35-60 yrs old and 2,337 men 45-60 yrs old)
      in the SU.VI.MAX cohort, selected at a national level in France. The overall mean
      dietary intake was estimated at 369 +/- 106 mg/day in men and 280 +/- 84 mg/day
      in women. 77 per cent of women and 72 per cent of men had dietary magnesium
      intakes lower than recommended dietary allowances; 23 per cent of women and 18
      per cent of men consumed less than 2/3 of these RDA. A strong positive
      correlation existed between energy and magnesium intake (r = 0.79; p < 10(-4)).
      Slight variations were observed according to socio-professional and educational
      levels and place of residence. Cereal products represented the main contribution
      in both men (21 per cent) and women (19.8 per cent). In men, the second source
      was represented by alcoholic beverages (11.7 per cent), which were a lower source
      of magnesium in women (5.5 per cent). Dairy products, vegetables, meat and
      poultry were the other main sources of dietary magnesium intake.

PMID- 9513930
TI  - Are age-related neurodegenerative diseases linked with various types of magnesium
      depletion?
AB  - Age-related human neurodegenerative diseases are a major social and medical
      problem. It is therefore logical to take into consideration every theory with an
      overall approach to neurodegenerative diseases. This environmental proposal
      relies mainly on data concerning the Western Pacific amyotrophic lateral
      sclerosis-Parkinsonism-dementia complex (WP ALS-PD) considered as 'a prototypal
      human neurodegenerative disease' and on extrapolation from it to the bulk of
      neurodegenerative diseases (NDD). NDD would be due to an accelerated ageing
      process in certain populations of neurons due to the noxious synergy of (1)
      increased environmental slow deleterious factors (such as slow toxins) and of (2)
      decreased environmental protective factors (Mg deficient intake particularly).
      First, it was observed that three apparently dissimilar conditions occurred at
      extraordinary high rates in the Guam area: motoneuron disease (ALS), Parkinson's
      disease (P) and Alzheimer's-like dementia (D). Next, several other foci of
      endemic ALS-PD were found in Asia and Oceania in three Western Pacific population
      groups. These included the Chamorro people in Mariana Islands (Guam and Rota),
      the Auyu and Jakai people of West New Guinea and the Japanese residents of the
      Kii peninsula (Honshu island). The post-Second World War decline of the
      occurrence of WP ALS-PD in all three high incidence disease foci coupled with the
      absence of demonstrable heritable or transmissible factors had led to focus the
      search for the cause of this degenerative disease on nontransmissible
      environmental factors that are disappearing as the susceptible population groups
      acculturate to modern way. Epidemiologic study has shown that preference for
      traditional Chamorro food is the only one of 23 tested variables significantly
      associated with an increased risk for PD. An early suggestion incriminated the
      toxic seed of the false sago palm (Cycas circinalis L) which was used in
      traditional food and medicine. Laboratory investigation of cycad seed revealed
      the presence of various toxins and particularly of an 'unusual' non protein
      aminoacid: L-BMAA (beta-N-methylamino-L-alanine), an excitotoxic aminoacid. This
      slow toxin presents some structural similarity to another 'unusual' excitotoxic
      aminoacid: L-BOAA (beta-N-oxalyl-amino-L-alanine), an exogenous neurotoxin
      present in the grass pea (Lathyrus sativus) whose excessive consumption may cause
      lathyrism. The excitotoxicity of both L-BMAA and L-BOAA mainly concerns non-NMDA
      receptors. The neurotoxicity of these aminoacids varies with experimental models
      failing to induce an experimental model akin to WP ALS-PD or displaying many of
      the motor-system and behavioral changes of WP ALS-PD. It may be due to the
      presence of physiological levels of bicarbonate or of various toxic cofactors:
      bio-organic such as cycasin or inorganic such as pollutant metals e.g. aluminum
      or manganese, together with the lack of protective factors (e.g. calcium and
      magnesium deficiencies). Combined Al intoxication with Ca-Mg deficiencies is a
      reasonable model to investigate the pathogenesis of neurodegenerative diseases
      and eventually to screen their treatments. It may also be considered as a model
      of magnesium deficit, but it does not concern simple magnesium deficiency
      reversible with mere oral physiological magnesium supplementation. Magnesium
      deficiency cannot result in neurodegenerative disease. Combined Al intoxication
      with Ca-Mg deficiencies is not reversible through physiological oral magnesium
      supplementation. It therefore constitutes a type of experimental magnesium
      depletion model, instrumental in the investigation of the pathogenesis of
      magnesium depletion and in the screening of its still unknown possible
      treatments. (ABSTRACT TRUNCATED)

PMID- 9513931
TI  - Cholesterol metabolism in human umbilical arterial endothelial cells cultured in
      low magnesium media.
AB  - Epidemiological and experimental studies have shown that magnesium is closely
      related to regulation of lipid metabolism, membrane structure and permeability,
      ion migration through cellular membranes, endocrine hormone and platelet
      function. The cause of atherosclerosis induced by magnesium deficiency has been
      suggested to be due to abnormal lipid metabolism, lipid peroxidation, a decrease
      of prostacycline produced by endothelial cells, and an increase of platelet
      aggregation. We found that the plasma from cardiac catheterized patients
      suffering from chest pains contained higher levels of oxysterols than age and sex
      matched patients free of chest pain. Studies with cultured arterial cells in
      media deficient in magnesium or containing oxysterols indicated that both
      magnesium and oxysterols have an important role in lipid metabolism in patients
      with coronary heart disease.

PMID- 9513932
TI  - VIIIth International Symposium on Magnesium, Heraklion, Greece, 5-9 October 1997.

PMID- 9513929
TI  - Magnesium deficit in a sample of the Belgian population presenting with chronic
      fatigue.
AB  - 97 patients (25 per cent males, ages ranging from 14 to 73 years, median 38
      years) with complaints of chronic fatigue (chronic fatigue syndrome, fibromyalgia
      or/and spasmophilia) have been enrolled in a prospective study to evaluate the Mg
      status and the dietary intake of Mg. An IV loading test (performed following the
      Ryzen protocol) showed a Mg deficit in 44 patients. After Mg supplementation in
      24 patients, the loading test showed a significant decrease (p = 0.0018) in Mg
      retention. Mean values of serum Mg, red blood cell Mg and magnesuria showed no
      significant difference between patients with or without Mg deficiency. No
      association was found between Mg deficiency, CFS or FM. However serum Mg level
      was significantly lower in the patients with spasmophilia than in the other
      patients.

PMID- 9513933
TI  - Mosquito carboxylesterases: a review of the molecular biology and biochemistry of
      a major insecticide resistance mechanism.
AB  - The major mechanism of organophosphorus insecticide resistance in Culex
      mosquitoes involves the elevation of one or more esterases. The general mechanism
      underlying this resistance is the amplification of the structural genes. This
      review covers the classification of the mosquito esterases in the context of
      classical esterase nomenclature. The function of the amplified esterases and the
      structure of the amplified DNA on which they occur are also described.
      Implications of information on the esterase amplicons are discussed in relation
      to the evolution and migration of insecticide resistance in Culex.

PMID- 9513934
TI  - Sugar feeding and fluid destination control in the phlebotomine sandfly Lutzomyia
      longipalpis (Diptera: Psychodidae).
AB  - Sandfly feeding behaviour and destination of coloured sugar meals in the gut of
      Lutzomyia longipalpis were investigated with particular attention to the role of
      the crop. Sandflies were able to ingest sugar from liquid drops,
      microcapillaries, a slice of pear and even sugar powder. In most cases the flies
      adopted a 'sugar feeding mode' with raised palps. As the fruit dried, flies of
      both sexes fed by piercing the tissue with the proboscis. All sugar-fed flies had
      a full crop plus a small amount of sugary fluid in the thoracic mid-gut, i.e.
      past the stomodaeal valve. Dissections of flies interrupted during feeding showed
      that the very first trace of sugar passed through the stomodaeal valve, but that
      the rest of the meal was diverted into the crop. This suggests that closure of
      the stomodaeal valve is initiated only after a small volume of sugar solution has
      passed through it.

PMID- 9513935
TI  - Population structure of Andean Triatoma infestans: allozyme frequencies and their
      epidemiological relevance.
AB  - Triatoma infestans (Hemiptera: Reduviidae) from 22 Andean localities in Bolivia
      (n = 968) and Peru (n = 37) were analysed by multi-locus enzyme electrophoresis.
      Among 12 gene-enzyme systems analysed, GPD, 6GPD and PGM were polymorphic, ACON,
      G6PD, GPI, 1DH, LAP, MDH, ME, PEP-A and PEP-B were monomorphic. Allozyme
      frequencies were analysed in relation to geographical and climatic factors, and
      the presence or absence of Trypanosoma cruzi infection. At one locality
      (Vallegrande, Bolivia), the frequency of 6Pgd-1 was significantly higher in
      infected (41% of 85) than in uninfected (17% of 83) adult T. infestans, although
      no such difference was found among nymphs (n = 347). From other localities, only
      insects infected with T. cruzi were subjected to isozyme analysis. Populations of
      T. infestans within villages showed panmixia, while genetic differentiation of T.
      infestans between villages was correlated with the distance between them. The
      genetic structure of T. infestans natural populations followed an 'isolation by
      distance' model, involving a series of founder effects followed by genetic drift,
      rather than adaptation in response to differential selection pressures. This
      conforms with circumstantial evidence that T. infestans spread, mainly in
      association with recent human migrations, from a source, probably in southern
      Bolivia. Isoenzyme characterization of populations of T. infestans could be used
      to infer sources of re-infestation during the surveillance phase of control
      programs.

PMID- 9513936
TI  - Alary polymorphism in Triatoma spinolai and its possible relationship with
      demographic strategy.
AB  - Among collections of Triatoma spinolai from various sites in northern Chile,
      adults from coastal populations are invariably wingless, whereas inland
      populations show balanced alary polymorphism between wingless females and males
      that are either winged or wingless. Laboratory crosses showed that male offspring
      from normal-winged parents were always winged (88% long-winged) and those from
      long-winged male parents were all long-winged. The male offspring from wingless
      males always included winged males: 11/33 = 33%, of which 8/11 = 73% were long
      winged. An X-linked mutation is proposed to inhibit wing development. Field
      studies of population demography indicate that male alary polymorphism is
      advantageous in the desert environment of northern Chile.

PMID- 9513937
TI  - Mosquito density, biting rate and cage size effects on repellent tests.
AB  - Mosquito biting rates and the mean duration of protection (in hours) from bites
      (MDPB) of Aedes aegypti and Anopheles quadrimaculatus, using the repellent 'deet'
      (N,N-diethyl-3-methylbenzamide) on a 50 cm2 area of healthy human skin, were
      observed in small (27 l), medium (approximately 65 l) and large (125 l) cages
      containing low, medium or high densities of mosquitoes: respectively, 640, 128 or
      49 cm3 of cage volume per female. At the initial treatment rate of approximately
      0.4 microliter/cm2 (1 ml of 25% deet in ethanol on 650 cm2 of skin), the MDPB for
      deet against Ae. aegypti ranged from 4.5 to 6.5 h and was significantly less (5.0
      +/- 0.8 h) in large cages compared with medium (6.2 +/- 0.9 h) and small (6.2 +/-
      0.8 h) cages, regardless of the density. Against An. quadrimaculatus the MDPB for
      deet 0.4 microliter/cm2 was 1.5-8.0 h, less in small (3.7 +/- 2.3 h) and large
      (2.2 +/- 1.1 h) cages at medium (3.7 +/- 2.3 h) and high (2.5 +/- 1.7 h) mosquito
      densities, and was longest in medium cages (6.2 +/- 2.6 h) at low mosquito
      densities (5.8 +/- 2.8 h). With equinoxial photoperiodicity (light on 06.00-18.00
      hours) the biting rate was influenced by the time of observation (08.00, 12.00,
      16.00 hours) for Ae. aegypti but not for An. quadrimaculatus. For both species,
      the biting rate was inversely proportional to mosquito density and the MDPB. The
      shortest MDPBs were obtained in large cages with high densities of mosquitoes and
      longest protection times occurred in medium sized cages with low mosquito
      densities.

PMID- 9513938
TI  - The efficacy of entomopathogenic nematodes for controlling housefly infestations
      of intensive pig units.
AB  - The efficacy of the entomopathogenic nematodes Steinernema feltiae and
      Heterorhabditis megidis after formulation into a housefly bait was compared with
      a commercial bait formulation of methomyl for the control of houseflies in a U.K.
      pig farm. The housefly infestation was confined to the farrowing unit, which
      consisted of ten farrowing houses, where two adjacent houses were sequentially re
      stocked with pregnant sows at weekly intervals. Shortly after re-stocking, one
      house was baited with one of the nematode species and the other with methomyl.
      Significantly fewer flies (P < 0.05) were counted in the houses baited with
      either S. feltiae or H. megidis than those baited with methomyl. The efficacy of
      S. feltiae sprayed on to the manure was also compared with methomyl bait. Counts
      of houseflies carried out in the farrowing cycle before this treatment were not
      significantly different (P > 0.05); however, significantly fewer flies (P < 0.05)
      occurred after S. feltiae was sprayed. The efficacy of encapsulated S. feltiae
      was also compared with methomyl bait and no significant difference was observed
      (P > 0.05).

PMID- 9513940
TI  - Comparison of bednets treated with alphacypermethrin, permethrin or
      lambdacyhalothrin against Anopheles gambiae in the Gambia.
AB  - In the Gambian village of Saruja, where malaria is transmitted mainly by
      mosquitoes of the Anopheles gambiae complex, a trial was undertaken of the
      acceptability and efficacy of bednets treated with one of three pyrethroid
      insecticides--alphacypermethrin 40 mg/m2, permethrin 500 mg/m2 and
      lambdacyhalothrin 10 mg/ m2. Fewer mosquitoes were found alive under nets treated
      with insecticide than under control nets. Significantly more dead mosquitoes were
      found under nets treated with alphacypermethrin than under nets treated with
      permethrin or lambdacyhalothrin. Side-effects were reported by a proportion of
      the users of nets treated with each of the insecticides, but none were severe and
      their prevalence was similar between treatment groups. Unwashed nets treated with
      alphacypermethrin were more effective at killing anopheline mosquitoes in
      bioassays than nets treated with permethrin or lambdacyhalothrin. Killing
      activity was reduced when nets were washed, irrespective of which insecticide was
      used. Bednets treated with alphacypermethrin are well accepted, effectively
      killed anopheline mosquitoes and should therefore be evaluated for personal
      protection against malaria transmission.

PMID- 9513939
TI  - Permethrin-impregnated bednet effects on resting and feeding behaviour of
      lymphatic filariasis vector mosquitoes in Kenya.
AB  - The impact of permethrin-impregnated bednets on resting and feeding behaviour of
      mosquito vectors of Wuchereria bancrofti, causing human lymphatic filariasis was
      studied in six pairs of villages (treated and untreated) before and after
      intervention. The study villages were in Kwale District, near the coast of Kenya,
      where Bancroftian filariasis is highly endemic, transmitted by a combination of
      both anopheline and culicine mosquito vectors. Mosquitoes were collected weekly
      in each village, indoors (using pyrethrum spray catches) and outdoors (using pit
      traps) during 3-4 months following the long rainy season. Of the filariasis
      vector species of mosquitoes collected in 1994 before intervention. 33.6% were
      members of the Anopheles gambiae complex, 30% were An. funestus and 36.4% were
      Culex quinquefasciatus. PCR analysis of the An. gambiae complex species collected
      in 1995 demonstrated that 98.5% were An. gambiae sensu stricto. 1% An. arabiensis
      and 0.5% An. merus. Introduction of impregnated bednets in 1995 significantly
      reduced the number of indoor-resting An. gambiae s.l. by 94.6% and An. funestus
      by 96.7%, but there was no change in the number of Cx quinquefasciatus collected
      indoors. The number of outdoor-resting An. gambiae s.l. was significantly
      reduced, whereas densities of An. funestus and Cx quinquefasciatus remained
      unaffected outdoors. ELISA analysis of mosquito bloodmeals showed a shift from
      human to animal feeding after the introduction of treated nets. The human blood
      index (HBI) for indoor resting Cx quinquefasciatus was reduced from 93.1% to
      14.4%. Vector potential based on the HBI and mosquito density was estimated to be
      reduced by 99% for An. gambiae s.l., 98% for An. funestus and 97% for Cx
      quinquefasciatus and vectorial capacity would be suppressed even more by the
      impact on the vector survival rates (not measured). These results suggest that
      permethrin-impregnated bednets give effective personal protection against
      transmission of W. bancrofti by An. gambiae, An. funestus and Cx quinquefasciatus
      in East Africa.

PMID- 9513941
TI  - Effect of arena size on behaviour and mortality of the oriental cockroach Blatta
      orientalis in arenas with a cypermethrin deposit adjacent to harbourage access
      points.
AB  - Activity and survival of adult female Blatta orientalis was investigated using
      tagged cockroaches in periodically illuminated arenas (LD 12:12 h) with a
      harbourage at one end. The arenas were rectangular with a width of 50 cm and
      lengths up to 480 cm. A cypermethrin-treated plywood plate (50 x 11 cm) substrate
      across the harbourage access points caused cockroaches to be exposed to the
      insecticide deposit by tarsal contact as they entered or left the harbourage. The
      effects of varying arena length and cypermethrin concentration were tested at 28
      degrees C. The LC50 following 3 days exposure ranged from 5.7 to 11.8 mg/m2 on
      the plywood plate for arena lengths of 60 to 480 cm, respectively; cypermethrin
      at 30 mg/m2 produced 100% knockdown of B. orientalis within one 12 h dark period.
      During darkness, active cockroaches spent most time close to the harbourage or
      around food and water stations, at the far end of the arena, and made frequent
      returns into the harbourage. For arena length 120 cm, the mean duration of
      contact with treated plates during the first hour of the dark period was
      significantly less than contact time on untreated plates, but during 12 h the
      cumulative contact times were not significantly different between treated and
      untreated plates. During the first 4 h of the dark period, mean cockroach numbers
      on the treated plate declined as arena length increased, but not as rapidly as
      the mean number/unit area over the rest of the arena. The arena design is
      considered suitable for comparative testing of fast-acting neuroactive
      insecticide deposits against cockroaches.

PMID- 9513943
TI  - Comparative kinetics of bloodmeal intake by Triatoma infestans and Rhodnius
      prolixus, the two principal vectors of Chagas disease.
AB  - Chagas disease vector insects Triatoma infestans and Rhodnius prolixus (fifteen
      stage III nymphs per 4 litre cage) were allowed to feed on anaesthetized mice for
      1 h (control group), or on active non-anaesthetized mice (NAM) for 2, 4 or 8 h
      exposure. The bloodmeal size (weight increase) for both species was proportional
      to the duration of contact with NAM, due to ingestion of multiple small
      bloodmeals, up to 142% of control weight for T. infestans with 8 h exposure to
      NAM. The mean weight increase of T. infestans nymphs after 4 h contact with NAM
      was similar to that of the control group, whereas for R. prolixus, 8 h contact
      with NAM gave only 64% of the control value. For both species of insect, within 4
      h of feeding, > 20% of the bloodmeal weight was lost by defaecation and diuresis.
      The proportions of unfed nymphs and mortality during 2 h contact with NAM were
      significantly higher for R. prolixus, demonstrating better exploitation of the
      host blood source by T. infestans, apparently because during blood-feeding the
      latter insect species caused less irritation to the host.

PMID- 9513942
TI  - Mark-release-recapture experiments with Anopheles gambiae s.l. in Banambani
      Village, Mali, to determine population size and structure.
AB  - Mark-release-recapture experiments with Anopheles gambiae s.l. were performed
      during the wet seasons of 1993 and 1994 in Banambani, Mali. All recaptured
      mosquitoes were identified to species by PCR analysis and, when possible, by
      chromosomal analysis to chromosomal form. Two species of the An. gambiae complex
      were present: An. gambiae s.s. and An. arabiensis; their ratio differed greatly
      from one year to the next. Three chromosomal forms of An. gambiae s.s. were found
      -Bamako, Savanna and Mopti. The drier 1993 was characterized by a high frequency
      of An. arabiensis and of the Mopti chromosomal forms of An. gambiae s.s. These
      trends were consistent with large-scale geographical patterns of abundance along
      a precipitation gradient. We observed no difference in dispersal between the two
      species, nor among the chromosomal forms of An. gambiae s.s. Therefore, in this
      situation at least, it is reasonable to group such data on the An. gambiae
      complex as a whole for analysis. Population size of An. gambiae s.l. females in
      the village was estimated to be 9000-11,000 in 1993 and 28,000 in 1994. The
      corresponding numbers were somewhat higher when independently-derived values of
      daily survival were used. These were consistent with estimates of effective
      population size obtained from patterns of gene frequency change.

PMID- 9513944
TI  - Distribution of Borrelia burgdorferi s.l. spirochaete DNA in British ticks
      (Argasidae and Ixodidae) since the 19th century, assessed by PCR.
AB  - The distribution of Borrelia burgdorferi sensu lato, the Lyme borreliosis agent,
      was surveyed in British ticks in the collection of the Natural History Museum,
      London. Alcohol-preserved specimens of eight species of ticks known to attack
      humans were studied: Ixodes ricinus, I. hexagonus, I. uriae, I. trianguliceps,
      Dermacentor reticulatus, Haemaphysalis punctata, Rhipicephalus sanguineus and
      Argas vespertilionis. The sample comprised all life stages and originated from a
      wide range of host species, collection dates (1896-1994) and geographical
      localities in England, Scotland and Wales. Borrelia burgdorferi s.l. DNA,
      detected by a polymerase chain reaction that targeted the outer surface protein A
      gene, was found in all eight species. The overall proportion of PCR-positive
      specimens ranged from 7.8% for I. hexagonus (mostly from mustelids and hedgehogs)
      to 98.3% for I. uriae (mostly from seabirds). Borrelia burgdorferi s.l. DNA was
      found for the first time in the bat parasite A. vespertilionis (85.3%). The
      spirochaete is newly recorded in British populations of I. trianguliceps (97.4%,
      mostly from voles, mice and shrews), D. reticulatus (12.5% from dog and man) and
      R. sanguineus (30% from dogs and human dwellings). Of the four tick species with
      larvae available for testing, examples of I. ricinus, I. uriae and A.
      vespertilionis were PCR positive, as were significantly more nymphs than adults
      of I. ricinus, I. hexagonus and A. vespertilionis. Analyses showed that B.
      burgdorferi s.l. has been consistently present in British tick populations since
      at least 1897. Ticks positive for B. burgdorferi s.l. DNA were collected in all
      months of the year, throughout Britain, and were found on a wide range of mammal
      and bird species. PCR positivity does not prove vector or reservoir competence,
      but the use of archived material has demonstrated an extensive range of host-tick
      relationships involving B. burgdorferi s.l. in Britain for > 100 years.

PMID- 9513945
TI  - Larvicidal toxicity of Japanese Bacillus thuringiensis against the mosquito
      Anopheles stephensi.
AB  - Japanese isolates of Bacillus thuringiensis were screened for larvicidal activity
      against the mosquito Anopheles stephensi, the urban malaria vector of the Indian
      subcontinent. Among more than 30 strains identified, larvicidal activity causing
      > 80% mortality in 72 h was demonstrated for 41/1449 (2.8%) isolates. The
      majority of strains and isolates (97.2%) exhibited little or no larvicidal
      activity. Anopheles-active strains belonged to more than 12 H serotypes,
      especially H3ade (serovar fukuokaensis) and H44 (serovar higo). SDS-PAGE profiles
      of inclusion proteins showed 4 distinct types among 6 active strains examined.
      The most active Japanese isolates were H20 strain 89-T-34-14 (LC50 4.4
      micrograms/ml) and H44 serovar higo strain 74-E-45-24 (LC50 7.6 micrograms/ml),
      respectively, 13-fold and 23-fold less active than the international standard H14
      serovar israelensis (LC50 0.33 microgram/ml).

PMID- 9513946
TI  - Isolation of the spirochaete Borrelia afzelii from the mosquito Aedes vexans in
      the Czech Republic.
AB  - During the years 1993-1995, a total of 3580 culicine mosquitoes of six species
      were collected in South Moravia, Czech Republic, and examined by dark-field
      microscopy for the presence of borreliae. Females of Aedes cantans, Ae.
      sticticus, Ae. vexans, Culex pipiens and Cx pipiens biotype molestus (but not Ae.
      geniculatus or Culiseta annulata) harboured spirochaetes, the frequencies ranging
      from 0.7% to 7.8%. One isolate (BR-53) from Ae. vexans was identified as Borrelia
      afzelii genospecies. The potential role of mosquitoes in the epidemiology of Lyme
      borreliosis should be investigated.

PMID- 9513947
TI  - Development of Setaria labiatopapillosa in Aedes caspius.

PMID- 9513948
TI  - Cross-resistance to malathion in Cuban Culex quinquefasciatus induced by larval
      selection with deltamethrin.

PMID- 9513949
TI  - Electric nets for studying odour-mediated host-seeking behaviour of mosquitoes.

PMID- 9513950
TI  - Review, reevaluation, and new results in quantitative structure-activity studies
      of anticonvulsants.
AB  - This paper reviews and reevaluates all of the published QSAR treatments of
      anticonvulsants and extends them to a new relationship. This reveals that in
      almost all cases, the Clog P relationship plays a significant part in the QSAR
      relationship whether the data stems from receptor to whole animal studies. In
      some cases the steric factors (B5, B1, and L) are important and, in one case, the
      log VW relationship is of marginal importance. Electronic effects, except for the
      Hammett's constant sigma, are comparatively unimportant. This suggests that the
      receptors involved possess a special stereochemical and electronic feature: The
      aromatic ring and the nitrogen moieties (e.g., an amide group) are the primary
      binding groups. The study shows that log P, as calculated by the Clog P program,
      is suitable for this form of QSAR study. Log Po of 2 was found to be ideal for
      passive penetration of these agents into the CNS.

PMID- 9513951
TI  - Education of medicinal chemists in Departments of Medicinal Chemistry (U.S.A.).
AB  - The present state of faculties, student bodies, and curricula in departments of
      medicinal chemistry have been surveyed by questionnaire and analyzed in the
      context of perceptions of quality and content. The results reveal a healthy
      diversity of educational objectives and a broader range of educational objectives
      than those uncovered in previous surveys of the perceived needs of industrial
      departments of medicinal chemistry in their search for drug discovery personnel.

PMID- 9513952
TI  - [Salsolinol, 3-O-methyl-dopa and homovanillic acid in the cerebrospinal fluid of
      Parkinson patients].
AB  - Salsolinol is one of the dopamine-derived tetrahydroisoquinolines, supposed to be
      a potent dopaminergic neurotoxin, similar to MPTP. Its systemic administration
      induced parkinsonism in monkeys. The aim of the study was to compare the
      concentration of salsolinol and the metabolite of L-dopa, 3-O-MD, and the
      metabolite of dopamine, HVA, in the cerebrospinal fluid of patients with
      different degrees of parkinsonism, treated or nontreated with l-dopa. Lumbar CSF
      was obtained from 26 patients with Parkinson's disease (15 early and 11 advanced
      parkinsonism) and from six healthy controls. The presence of salsolinol, HVA and
      3-O-MD was assayed with a sensitive HPLC method employing C18 (Hypersil BDS)
      column. The analysis of the results demonstrated that the concentration of
      salsolinol was related to the degree of parkinsonism but not affected by l-dopa
      treatment. In contrast, HVA and 3-O-MD were significantly elevated in patients
      receiving l-dopa but did not correlate with the severity of parkinsonism. The
      results suggest that salsolinol in the cerebrospinal fluid does not originate
      from exogenous l-dopa and its elevation in cerebrospinal fluid may be an
      indicator of the advancement of parkinsonism.

PMID- 9513953
TI  - [Factors contributing to so-called idiopathic headaches].
AB  - The interest in factors that may trigger in some cases idiopathic headache has
      increased in recent years. This problem has not been discussed in Polish
      literature up to now. An analysis of precipitating factors in a group of 116
      patients: 70 with migraine, 30 with tension type of headache and 16 with cluster
      headache was conducted. In these groups: 60 patients (87%) with migraine, 24
      patients (80%) with tension type headache and 15 patients (94%) with cluster
      headache confirmed activity of precipitating factors was shown. Stress was the
      most frequently cited precipitant in all types of idiopathic headaches (migraine
      58%; tension type headache-53%; cluster headache-50%). Weather changes were in
      the second place. Excessive environmental factors, oversleep, some foods were
      also prominent factors.

PMID- 9513955
TI  - [Clinical picture of medial prolapse of a lumbar intervertebral disk].
AB  - Case records of one-hundred patients operated on for centrally prolapsed lumbar
      intervertebral disc were analyzed for establishing of typical clinical symptom
      complex. Despite the complexity and variety of clinical manifestations five
      groups of patients were isolated on the basic of their pain features and
      neurological deficit. Besides, for more exact diagnosis of prolapsed level, the
      neurological signs were analyzed in relation to these levels. This approach makes
      possible more precise diagnosis in practice important in view of the possible
      consequences of central prolapsed of intervertebral disc (PIVD).

PMID- 9513954
TI  - [Changes in the nervous system due to occupational metallic mercury poisoning].
AB  - At the Institute of Occupational Medicine and Environmental Health, during 12
      years, chronic mercury intoxication was diagnosed in 34 persons. There were male
      workers tending technological processes in which Hg was used as a catalyst
      (synthesis of acetic aldehyde and obtaining chlorine). The length of professional
      exposure was 13-34 years (mean 20.6). The patients were removed from the contact
      with Hg after Hg intoxication case was confirmed. During the following 11 years,
      24 of them were reexamined in the clinical department 2-4 times. The clinical
      picture of the poisoning consisted mainly of neurasthenic, cerebellar (30
      persons), psychoorganic symptoms (20 persons) and behavioural changes
      (irritability, aggressive states). Headaches, sleep and recent memory
      disturbances, progressive behavioral changes, dizziness, were the most frequent
      complaints. The authors stressed the irreversibility of central nervous disorders
      despite cessession of the exposure to Hg. The degree of cerebellar intensity
      changes did not handicap examined patients. This is especially important to show
      the difference between the above described clinical picture of Hg intoxication
      and multiple sclerosis.

PMID- 9513956
TI  - [Clinical and radiological analysis of lumbar spine stability after
      hemilaminectomy and laminectomy in cases of lumbar disk excision with
      simultaneous interbody fusion].
AB  - 108 patient were operated on the Neurosurgical Department of the Military
      Clinical Hospital in Wroclaw since 1989 till 1991. The stability of the lumbar
      spine after hemilaminectomy and laminectomy with disc excision and interbody
      fusion was analysed. The period after operation ranged from 6 months to 2 years.
      Signs of clinical and radiological instability were the base of the study.
      Respective segmental motions in maximal ante- and retroflexion were calculated.
      Horizontal intercorporal dislocation was assessed. No signs of instability where
      found in the analysed material. The results after laminectomy and hemilaminectomy
      were similar. The failures were not caused by instability.

PMID- 9513958
TI  - [Neurological syndromes in HIV patients. Part III -- HIV-related diffuse diseases
      of the central nervous system].
AB  - The last part of the review of the neurological syndromes observed among people
      who are HIV-infected deals with AIDS Dementia Complex, viral (CMV, HSV, VZV)
      encephalitides and cryptococcal meningitis and other less frequent diseases.
      Clinical presentation, neuropathology, diagnostic procedures and treatments are
      described. Diagnostic algorithm for central nervous system diseases in people
      with HIV is included. The main purpose of the present reviews is to pursue the
      common ground regarding treatment and diagnostic procedures with consulting
      neurologists and neurosurgeons for future cooperation in a growing area of HIV
      related neurology.

PMID- 9513959
TI  - [Dialysis therapy and central nervous system disturbances].
AB  - Complications connected with chronic dialysis therapy and manifesting themselves
      as symptoms of central nervous system lesion, are presented. A special attention
      was paid to dialysis encephalopathy, to dialysis disequilibrium syndrome and to
      the vascular lesion of brain, that of the dialysis.

PMID- 9513957
TI  - [The assessment of therapeutic effectiveness of paravertebral blockades in
      patients with painful radicular syndromes in discopathy and in lumbar spine
      spondylosis].
AB  - A group of 103 patients were examined for radicular painful syndromes in lumbar
      discopathy and lumbar spondylosis. Fifty-eight were treated by placing them in
      spine-decompressing position, traction and therapeutic exercises. The group of 45
      patients had additionally paravertebral blockade (steroid + a local anaesthetic).
      In the blockade group the therapeutic effects were better, with rapid reduction
      of acute pain, with wellbeing improvement and better comfort, which facilitated
      further stages of the treatment. This made possible shortening of hospital stay
      by 20%, on average, as compared with the group without blockade. In patients with
      shorter lasting radicular pains (below 2 months) the results after paravertebral
      blockade were significantly better than in cases with longer duration of pains (2
      6 months).

PMID- 9513960
TI  - [Subcortical dementia and the frontal lobe syndrome].
AB  - Subcortical dementia is a clinical syndrome incorporating disorders of cognitive
      and affective sphere, which is caused by organic damage to subcortical
      structures. The syndrome is usually connected with Progressive Supranuclear
      Palsy, Huntington Disease, Parkinson's Disease. Subcortical dementia is mainly
      characterized by: slowing down of psychic functions and impairment of their
      precision, disorders in the ability to use achieved knowledge and personality
      changes. Most authors stress the fact that similar cognitive and emotional
      personality defects are observed in cases of frontal cortex damage. Recent
      research points to the existence of functional subcortical-prefrontal circuits
      which regulate human behaviour. There is a link between subcortical dementia and
      functional or structural break of one or more cortical-subcortical connections.
      Attention is also called to disorders in certain neurotransmitting systems
      (dopaminergic, acetylcholinergic) as well as to brain hypometabolism in basal
      ganglia, thalamus and prefrontal cortex.

PMID- 9513961
TI  - [Pathogenesis and psychosocial consequences of post-concussion syndrome].
AB  - About 35% of subjects with head injury (HI) suffer from postconcussion syndrome
      (PCS). These disturbances can be chronic or even permanent. Such patients are
      discharged from hospital without any apparent problems, but it is often the case
      that their families, and sometimes even they themselves, start to notice the
      emergence of new problems. They may exhibit affective changes, such as thinking
      that they are worthless, alone and without any future perspectives. When they are
      left without the help of specialists and/or family and friends, their problems
      gain even greater significance. PCS includes subjective physical complaints (i.e.
      headache, dizziness) and cognitive, emotional and behavioral changes. PCS
      influences all areas of the patient's life. Subjects who have sustained head
      injury often have problems with marital relationships, maintaining of
      independence, employment, leisure activities and other functions which are
      related to social adjustment. Various studies have attempted to predict the post
      injury status of HI patients from information available, such as data on the
      severity of head injury, the duration of post-traumatic amnesia (PTA) and the
      results of neuropsychological assessment. This kind of prediction is important in
      planning of rehabilitation services and thus improving the kind of help available
      to survivors of HI. Early prediction of post-injury psychological status may also
      help the patient and his family in coping with the difficulties related to the
      trauma. We know a great deal about head injury and its consequences, but many
      questions still need to be answered. Among these are issues such as: the role of
      neurobehavioral data in the prediction of outcome for HI patients, the
      identification of variables determining the extent of PCS and the search for
      reliable factors which may influence future employment or school status. The
      assessment of patients for invalidity and other social security benefits also
      requires a more rational approach, based on the data available.

PMID- 9513962
TI  - [Spontaneous intracerebral hematomas].
AB  - The choice of treatment in spontaneous intracerebral haematomas has always been
      controversial. As indications to surgery should be regarded: location and size of
      haematoma, shifting of midline structures and deterioration of consciousness. The
      results of treatment are worsened by deep location of haematoma, especially in
      thalamus and brain stem region, very big size, primary serious condition, very
      advanced age of the patient and some metabolic diseases like liver dysfunction.
      It is difficult to establish fixed rules of treatment of spontaneous
      intracerebral haematomas and the decision depends mainly on the experience of the
      surgeon.

PMID- 9513963
TI  - [A case of multiple system atrophy treated with erythropoietin].
AB  - The patient, a women aged 52, with a three-year history of treatment for arterial
      hypotension, was admitted to hospital because of progressing worsening of
      symptoms. The whole clinical syndrome made possible the recognition of multiple
      system atrophy as the cause of her symptoms. In view of failures in previous
      treatment it was decided to give her erythropoietin injections for four weeks.
      The treatment led to improvement of her status. The authors discuss the probable
      action mechanism of erythropoietin in this case.

PMID- 9513964
TI  - [Arteriovenous angioma of the cerebellum associated with trigeminal neuralgia].

PMID- 9513965
TI  - [A case of left atrial myxoma with cerebral embolism].
AB  - A case of myxoma situated in the left atrium associated with cerebral embolism in
      a 7-year-old female patient is reported. The diagnosis was made on the basis of
      clinical examination and laboratory investigation (echocardiography). Attention
      is called to the value of echocardiography in young patients with cerebral
      embolism.

PMID- 9513966
TI  - [Diagnostic difficulties in a case of mitochondrial myopathy in a 51-year-old
      woman].
AB  - A case of mitochondrial myopathy in a 51-year-old woman is reported. External
      ophthalmoplegia, presence of persistent thymus and electrophysiologic
      investigation suggested myasthenia gravis. Electron microscopic examination of
      muscle biopsy showed changes typical of mitochondrial myopathy.

PMID- 9513967
TI  - [Perimesencephalic non-aneurysmal subarachnoid hemorrhage. Case report].
AB  - A case of perimesencephalic non-aneurysmal subarachnoid haemorrhage is reported.
      The patient was a 54-year-old women, after spontaneous subarachnoid haemorrhage
      with negative cerebral angiography. Internal hydrocephalus due to haemorrhage
      developed and ventriculo-atrial shunt was inserted. Outcome is presented and the
      possible causes of bleeding are discussed.

PMID- 9513968
TI  - [Delayed post-traumatic intracerebral pneumatocele: a case report and literature
      review].
AB  - In this report, the author presents an unusual case of a 19-year-old man with
      delayed intracerebral pneumatocele following a fronto-basal trauma. Clinically
      the patient demonstrated the frontal syndrome. The diagnosis was established by
      CT and plain skull X-ray. There was a 7-week interval between the trauma itself
      and the diagnosis of intracerebral pneumatocele. The patient underwent surgical
      intervention and the pneumatocele resolved after operation. During the operation
      it was found that the intracerebral pneumatocele in the right frontal lobe
      communicated with the ipsilateral ethmoidal sinus. The postoperative course was
      uneventful. The coincidence of a fronto-basal trauma and contusion of brain may
      lead to this kind of complications. The author believes that, surgical
      intervention in this circumstances is recommended.

PMID- 9513969
TI  - [Pleural cavity as an alternative for cerebrospinal shunting in hydrocephalic
      treatment].

PMID- 9513970
TI  - Neuroendocrine control of the gonadotropic function of the hypophysis in
      experimental diabetes.
AB  - The stability of the function of the reproductive system depends on a multitude
      of factors of the internal and external milieux. Serious disturbances in its
      function, with alterations in carbohydrate homeostasis, underlie such diseases as
      diabetes mellitus. Disturbances to the functional activity of the reproductive
      system in laboratory animals with diabetes are known to be associated not only
      with destructive changes in the gonads, but also with dysfunction of the
      hypothalamo-hypophyseal complex [9, 11]. Published data show that these lesions
      have different severities in male and female individuals [7, 8]. The question of
      the extent to which lesions due to the diabetic state depend on the level of sex
      steroids and insulin in the body thus far remains unanswered. Unlike the
      situation in males, females are characterized by cyclic changes in the activity
      of the reproductive system. Thus, it is possible that differences in the
      regulation of gonadotropic function in male and female rats, observed in normal
      animals, could explain their different sensitivities to diabetes. Thus, we
      elected to carry out various studies of the functional activity of the
      hypothalamo-hypophyseal-gonadal system in male and female rats with experimental
      diabetes induced by administration of streptozotocin (STZ).

PMID- 9513971
TI  - Functional rearrangements in the human brain during emotional self-regulation
      with biological feedback.
AB  - The concept that functional psychopathology producing phobic syndromes is
      mediated by a specific deficiency in the integrative activity of the brain as a
      loss or partial limitation of the ability to recognize subjective experiences was
      used to develop a special method for mobilizing the selective attention of
      patients to the time course of subjective states. The fact of recognition of a
      state was demonstrated by the patient's ability to reproduce it by achieving
      specific parameters in a biological feedback test based on skin electrical
      responses. Success was positively reinforced by avoidance of an anxiously
      expected electrical stimulus. After successful training, patients could
      spontaneously adaptively correct their general daily behavior. Computer analysis
      of EEG traces revealed the specific structural-functional features of various
      states provoked during training.

PMID- 9513972
TI  - Structural basis for the functional specialization of the pallidal complex of the
      cat brain.
AB  - Experiments carried out on 30 cats using retrograde axonal transport of markers
      (horseradish peroxidase and luminophores) were used to study the organization of
      the afferent projection system of the pallidal complex (the globus pallidum, the
      entopeduncular nucleus, the ventral pallidum) formed by fibers from functionally
      different cortical and subcortical structures (the ventral tegmental area, the
      substantia nigra, the amygdaloid body). The distribution of afferent projection
      fibers in this complex of nuclei led to identification of the following zones: a
      "limbic" zone, corresponding to the ventral pallidum, and a "motor" zone,
      corresponding to the caudal part of the globus pallidum. On the one hand, the
      features of the afferent organization as demonstrated here can be regarded as a
      structural basis for the functional heterogeneity of the pallidal complex; on the
      other, significant regions within these structures (the rostral part of the
      globus pallidum and the entopeduncular nucleus) were found to receive projection
      fibers from functionally different structures, suggesting the existence of
      convergence and integration processes in these regions.

PMID- 9513973
TI  - Effects of controllable and uncontrollable stresses on the receptor binding of
      dexamethasone in the hypophysis and hippocampus of rats with different behavior
      strategies.
AB  - The effects of controllable and uncontrollable stress on the receptor binding of
      dexamethasone in the hypophysis and hippocampus were studied in KHA and KLA rats,
      lines selected for the ability to development of active escape. Presentation of
      the controllable stimulus led to a significant reduction in receptor binding of
      dexamethasone in the hippocampus with significant changes in the plasma
      corticosterone concentration and receptor binding in the hypophysis. KLA rats
      were sensitive both to the controllable and the uncontrollable stresses, with
      increases in plasma corticosterone and receptor binding of dexamethasone in the
      hypophysis. It is concluded that receptor binding of dexamethasone in the
      hippocampus and hypophysis depend not only on the behavioral strategy of the
      animal, but also on the possibility of controlling the situation.

PMID- 9513974
TI  - Effect of low-intensity millimeter-range electromagnetic irradiation on the
      recovery of function in lesioned sciatic nerves in rats.
AB  - The effects of electromagnetic irradiation (EMI) of wavelength 5.6 mm (frequency
      53.57 GHz) and power density 4 mW/cm2 on the recovery of function in damaged rat
      sciatic nerve were studied; damage was produced by nerve section followed by
      microsuturing. Irradiation was applied to the skin of the thigh in the area of
      suturing. Total action potential (TAP) recording from the nerve was used to study
      the functional properties of regenerating nerve fibers five months after
      lesioning. These experiments demonstrated that EMI had a stimulatory effect on
      regenerative processes in the nerve, in terms of 25-30% increases in the rate of
      action potential conduction along nerve fibers, with increases in TAP amplitude.

PMID- 9513975
TI  - Conditioned reflex responses of the sympathetico-adrenal system to an aversive
      taste stimulus.
AB  - Studies were carried out on male and female rats in which the effects of isolated
      presentation of a conditioned stimulus (a saccharine solution) to which the
      animals had previously developed conditioned reflex taste aversion (RTA) on the
      level of urinary catecholamine secretion were determined. The studies showed that
      presentation of an aversive taste stimulus without reinforcement by a negative
      stimulus increased the levels of urinary adrenaline, noradrenaline, and dopamine
      secretion; this repeated, albeit more weakly, the effects of the negative
      reinforcement (angular acceleration) used for development of RTA. After
      presentation of the isolated aversive taste stimulus, the greatest increase in
      catecholamine excretion affected adrenaline, which indicates an anxiety state
      (fear). There was also a significant increase in noradrenaline excretion in these
      conditions. The accompanying increase in dopamine excretion in experimental and
      control animals showed this change to be largely nonspecific in nature, and to
      result from the experimental procedures. Isolated presentation of the conditioned
      taste stimulus elicited significantly greater increases in urinary catecholamine
      excretion in males than in females. It is suggested that the time for which the
      RTA is retained could be increased by activation of the sympathetico-adrenal
      system resulting from presentation of the nonreinforced taste stimulus which had
      acquired aversive properties.

PMID- 9513976
TI  - Brain catecholamines and the hypothalamo-hypophyseal-adrenocortical system in
      inherited arterial hypertension.
AB  - Rats with inherited stress-induced arterial hypertension (NISAG rats) and
      normotensive Wistar rats were used for studies of age-related changes in arterial
      pressure (BP), in the activity of the hypothalamo-hypophyseal-adrenocortical
      system (HHAS), and noradrenaline levels in brain structures involved in
      regulating these functions, with the aim of identifying possible relationships
      between them. It is suggested that the noradrenaline deficiency seen at the age
      of four weeks in the hypothalamus and medulla oblongata in NISAG rats is involved
      in the pathogenesis of hypertension and in disturbing the function of the HHAS.
      Transient increases in brain catecholamine synthesis in the fourth week of life
      lead to prolonged reductions in BP and complete recovery of HHAS responses to
      stress in adult animals. Correction of BP and HHAS function is accompanied by
      changes towards the normal in noradrenaline levels in the hypothalamus and
      medulla oblongata and in the numbers of alpha 1-adrenoceptors in the medulla
      oblongata.

PMID- 9513977
TI  - Organization of afferent and efferent projections in the hypothalamic subiculum
      supraoptic region system in the rat hypothalamus.

PMID- 9513978
TI  - Neuron discharges in the rat auditory cortex during electrical intracortical
      stimulation.
AB  - Studies were carried out in rats anesthetized with ketamine or nembutal, with
      recording of multicellular activity (with separate identification of responses
      from individual neurons) in the primary auditory cortex before and after
      electrical intracortical microstimulation. These experiments showed that about
      half of the set of neurons studied produced responses to short tonal bursts,
      these responses having two components-initial discharges arising in response to
      the sound, and afterdischarge occurring after pauses of 50-100 msec.
      Afterdischarges lasted at least several seconds, and were generally characterized
      by a rhythmic structure (with a frequency of 8-12 Hz). After electrical
      microstimulation, the level of spike activity increased, especially in
      afterdischarges, and this increase could last up to 4 h. Combined peristimulus
      histograms, cross-correlations, and gravitational analyses were used to
      demonstrate interactions of neurons, which increased after electrical stimulation
      and were especially pronounced in the response afterdischarges.

PMID- 9513979
TI  - gamma-Aminobutyric acid levels in the intercellular space in the nucleus
      accumbens of the rat brain during a nociceptive conditioned response.
AB  - Studies on Lister rats, using intracerebral dialysis in behaving animals combined
      with high-performance liquid chromatography with electrochemical detection,
      showed that the development and realization of an emotional conditioned response
      were accompanied by increases in the gamma-aminobutyric acid (GABA) levels in the
      extracellular space of the medial part of the nucleus accumbens. Regression
      analysis demonstrated that measures of investigative behavior (horizontal
      movements, rearings, and sniffing and grooming times) during quenching of the
      emotional conditioned response (but not on presentation of the experimental
      chamber to control rats) correlated with individual changes in the extracellular
      GABA levels in the nucleus accumbens. Thus, this is the first report of in vivo
      recording of changes in GABA levels in the extracellular space of the brain
      during realization of normal behavior.

PMID- 9513980
TI  - Inactivation kinetics of sensory neuron sodium channels depend on the type of
      hydrogen ion buffer.
AB  - Tetrodotoxin-sensitive and tetrodotoxin-resistant sodium currents were studied in
      rat dorsal root ganglion neurons using a patch-clamp method. The type of hydrogen
      ion buffer used was found to affect the kinetics of the inactivation process.
      Tris ions irreversibly bound to the inactivation gating apparatus, accelerating
      the decay in the trailing front of the ion current. The characteristics of this
      process were clearly nonlinear in this buffer. In HEPES buffer, the inactivation
      dynamics were slowed for both types of channel studied. Unlike results obtained
      with tris buffer, there were no sharp changes in the characteristics as compared
      to those obtained immediately after puncture of the cell membrane. The advantages
      of using HEPES buffer for studies of the inactivation gating processes of sodium
      channels are discussed.

PMID- 9513981
TI  - Electrophysiological analysis of the morphofunctional organization of the limbic
      control of magnocellular neurosecretory nuclei in the rat hypothalamus.
AB  - The effects of electrical stimulation of the ventral hippocampus, ventral
      subiculum, and corticomedial amygdala were used to obtain a general and
      comparative assessment of the organization of efferent outputs of limbic system
      structures to the magnocellular neurosecretory nuclei of the hypothalamus, i.e.,
      antidromally identified neurosecretory cells and other groups of identified
      neurons in these nuclei and in the perinuclear zones. These studies showed that
      different efferent outputs of the hippocampal formation provide differential
      control of spike activity of neurosecretory cells in the supraoptic nucleus, with
      excitatory pathways from the ventral hippocampus and inhibitory pathways from the
      subiculum. The effects of the amygdala on neurosecretory cells of the
      paraventricular nucleus were shown to be excitatory, though they were less
      significant than the excitatory and inhibitory effects of the hippocampus. It was
      demonstrated that in general, the effect of limbic structures are addressed
      predominantly to cells which do not project to the posterior lobe of the
      hypophysis. Projections were mostly to interneurons, which, as convergence sites
      for excitatory influences both from limbic structures and neurosecretory cells,
      may thus be responsible for the involvement of the latter in integrative brain
      functions.

PMID- 9513982
TI  - Functional mapping of the motor cortex of the white mouse by a microstimulation
      method.
AB  - Studies on 33 anesthetized white mice were used to determine the motor
      representation of facial muscles and limb muscles by an intracortical
      microstimulation method. Microstimulation produced predominantly ipsilateral
      movement responses of facial muscles and contralateral responses in fore- and
      hindlimb muscles. Low-threshold stimulation in the left and right hemispheres
      showed a clear asymmetry of the motor representation of the facial muscles.
      Movement responses of the hindlimbs were obtained on microstimulation of the
      frontal regions of the neocortex, demonstrating the existence of multiple motor
      representations of muscles in the neocortex.

PMID- 9513983
TI  - Simple apparatus for the electrical cleaning of glass microelectrodes.

PMID- 9513984
TI  - Distribution of nitric oxide synthetase in rat cerebral cortex cells.

PMID- 9513986
TI  - Ten steps to avoid fecal incontinence secondary to fourth-degree obstetrical
      tear.

PMID- 9513985
TI  - Neurochemical characteristics of neurons of the human hippocampal formation.

PMID- 9513987
TI  - Methods of creating pneumoperitoneum: a review of techniques and complications.
AB  - The existence of numerous techniques for the creation of pneumoperitoneum at
      laparoscopy indicates that none have been proven totally efficacious or
      complication free. These methods include the standard technique of insufflation
      after insertion of the Veress needle via the umbilicus or less commonly via the
      transfundal or transforniceal routes, open laparoscopy involving dissection
      through the linea alba and opening of the peritoneum under direct vision, and
      direct trocar insertion as well as variations on these techniques. After
      reviewing the methods available and surveying the existing data concerning the
      rates of failure and complications, we conclude that no single technique can
      claim to be overwhelmingly superior, and that laparoscopists should, therefore,
      acquaint themselves with at least two of these techniques. Finally, we recommend
      a large-scale combined survey by the colleges of obstetricians and gynecologists
      and surgeons on rates of failure and complications of the varied approaches of
      abdominal entry for laparoscopy.

PMID- 9513988
TI  - Bladder injury during laparoscopic surgery.
AB  - The objective of this review is to present the incidence of latrogenic bladder
      injury associated with diagnostic and/or operative laparoscopic surgery; to
      determine the type of primary laparoscopic operation, the time at which the
      reported injuries occurred, the location of injuries, and the method(s) used to
      repair those injuries; to decide which laparoscopic procedure carries the highest
      risk for bladder injury; and to establish the most frequent surgical instruments
      with which injuries happened. World literature published between 1970 and 1996
      was reviewed. The appropriate Medical Subject Heading (MeSH) terms were selected
      and used in a search of the MEDLINE, ACOGNET, OVID Compact Disk Version database.
      A total of 1372 articles on laparoscopic surgery complications were reviewed. Of
      that number, a total of 77 articles identified bladder injuries, and these were
      analyzed for the objectives of this study. There are a wide range of bladder
      injuries during laparoscopic procedures. In the studied articles, the incidence
      of bladder injury during laparoscopic procedures ranged from 0.02 to 8.3 percent
      of cases. Most frequently, these injuries occurred during laparoscopic-assisted
      vaginal hysterectomy. Sharp electrosurgical dissection was the leading instrument
      causing injury. An intraoperative diagnosis of bladder injury was made in 53.24
      percent of all bladder injury cases. The bladder dome was the most commonly
      injured structure. Less than half (29.87 percent) of the bladder injuries were
      corrected laparoscopically.

PMID- 9513989
TI  - Intra- and early postpartum ultrasonography: a review. Part II.
AB  - Part II is a continuation of the preceding segment, which appeared in the
      previous issue (Survey 1998;53:000-000). This part presents data pertaining to
      ultrasound-guided procedures (invasive and noninvasive), physiology (fetal
      behavior), intrapartum hemorrhage, the third stage of labor, post-partum
      hemorrhage, and postcaesarean ultrasonography. In addition, this article includes
      data regarding nonobstetric ultrasound including anesthesiology, catheter
      placement, venous air embolism, effect of epidural anesthesia on uterine blood
      flow, and urinary retention. Finally, this part presents ultrasonographic data of
      the maternal cerebral circulation in preeclampsia/eclampsia and of the maternal
      deep venous system.

PMID- 9513990
TI  - Observation of geometric structure of collagen molecules by atomic force
      microscopy.
AB  - Atomic force microscopy was used to study the geometric structure of collagen
      fibrils and molecules of rat calcanean tendon tissues. The authors found that the
      diameter of the fibrils ranged from 124 to 170 nm, and their geometric form
      suggested a helical winding with spectral period from 59.4 to 61.7 nm, close to
      the band dimensions reported by electron microscopy. At high magnification, the
      surface of these bands revealed images that probably correspond to the almost
      crystalline array of collagen molecules, with the triple helix structure almost
      visible. The typical helix width is 1.43 nm, with main periods of 1.15 and 8.03
      nm, very close to the dimensions reported by X-ray diffraction.

PMID- 9513991
TI  - Characterization of F VIII concentrates produced by two methods incorporating
      double virus inactivation.
AB  - The trend toward the production of high purity factor VIII concentrates for
      clinical use is still in progress. Although all plasma derivatives must undergo
      viral inactivation procedures, the possibility of transmission of viral diseases
      is not completely eliminated. In order to reduce such risk, we have included
      double virus inactivation in the procedure of factor VIII concentrate production.
      In a scale-up procedure for isolation of factor VIII cryoprecipitate, two methods
      were used. The first is based on the chromatographic purification of factor VIII
      after pasteurization of cryoprecipitate solution and solvent/detergent (S/D)
      inactivation of viruses. The second is based on multistep precipitation of factor
      VIII by sodium chloride and glycine. Viral inactivation was performed by
      combination of S/D treatment and heating of final freeze-dried product 30 min at
      100 degrees C. The typical yield of factor VIII activity in the freeze-dried
      product was about 20% for the first method, and 25-30% for the second.
      Electrophoretic analyses of both factor VIII preparations by SDS-PAGE and IEF
      show very low content of contaminant proteins, in accordance with observed 400
      650-fold increase of their specific activity over plasma. Both factor VIII
      products were stable in the liquid state for more than 24 h at room temperature.
      The final products, after double viral inactivation, are considered to be
      suitable for clinical evaluations.

PMID- 9513992
TI  - HIV/AIDS and children, youths, and families: lessons learned. Introduction.

PMID- 9513993
TI  - HIV infection and children: a medical overview.

PMID- 9513994
TI  - Factors associated with parents' decision to disclose their HIV diagnosis to
      their children.
AB  - Parents report that trying to decide whether or not to disclose their HIV
      diagnosis to their children is as emotionally charged as learning of the
      diagnosis itself. As part of a larger study, interviews were conducted with 17
      parent-child dyads recruited from patients being treated at the National Cancer
      Institute to understand the factors that affect the process of disclosure of a
      parent's HIV diagnosis and its consequences. Parents and HIV-infected children
      were also interviewed and were administered several standardized measures for
      collecting information on parental depression, family environment, and social
      support satisfaction. The factors associated with a parent's decision to disclose
      his or her diagnosis to the children, and implications for clinical practice and
      future research, are discussed.

PMID- 9513995
TI  - Parental loss due to HIV: caring for children as a community issue--the
      Rochester, New York experience.
AB  - The number of children in the United States who will lose a parent to AIDS is
      increasing. Permanency planning to help families affected by AIDS includes case
      management, mental health, medical care, child welfare, and legal services. These
      services are provided by a number of different professions, and have largely been
      reactive and noncoordinated. This article presents the efforts of one community
      in a midsize city to develop and implement a multidisciplinary coordinated plan
      for providing services to children affected by the illness or death of a parent
      from HIV/AIDS.

PMID- 9513996
TI  - Custody planning with HIV-affected families: considerations for child welfare
      workers.
AB  - Most of the literature on permanency planning is based on the assumption that HIV
      infected parents have custody of their children. A growing number of children
      entering child protective services, however, have an HIV-infected parent. Whether
      reunification or adoption is the permanency goal, these parents are concerned
      about their children's future after the parents' death. This article is drawn
      from research on custody planning with HIV-infected parents, from clinical
      literature and experience, and from a training curriculum for child welfare
      workers developed and implemented by the author. The lessons learned about
      custody planning with HIV-involved families are applied to practice with families
      who are involved with the state because of abuse or neglect of their children.

PMID- 9513997
TI  - Improving permanency planning in families with HIV disease.
AB  - This article describes two distinct service models developed for providing mental
      health and custody-planning services to families with advanced HIV disease or
      AIDS. Project Talk uses cognitive behavior techniques with groups of parents and
      their teenage children (ages 12 to 18). Project Care employs a psychoeducational
      approach to counseling mothers and children (ages 8 to 11) in their homes. While
      both models have a number of common characteristics, they also have unique
      strengths and limitations. Each is likely to play a role in providing services to
      a portion of the population facing the need to develop permanency plans for
      surviving children. Both models are being evaluated in separate longitudinal
      studies to assess the mental health outcomes of the children and the models'
      effectiveness in helping parents to plan for their futures.

PMID- 9513998
TI  - Correlates and distribution of HIV risk behaviors among homeless youths in New
      York City: implications for prevention and policy.
AB  - Homeless youths are at high risk for poor health outcomes, including repeated
      exposure to STDs and high rates of unplanned pregnancies, untreated TB, HIV
      infection, and accelerated immune dysfunction associated with AIDS. This article
      examines the nature and distribution of HIV-risk behavior in a broad, street
      based sample of homeless and runaway youths in New York City (N = 929). Although
      street youths in general are shown at high risk, the highest risks nest within
      older age segments of the male street youth population. Paradoxically, these
      youths are least likely to be in contact with prevention services. The data
      demonstrate the need to reconsider the use of chronological age as a determinant
      for service eligibility and to reconfigure funding streams so as to more
      effectively and consistently target older and more vulnerable youths.

PMID- 9513999
TI  - HIV prevention for youths in independent living programs: expanding life options.
AB  - The incidence of human immunodeficiency virus (HIV) infection among adolescents
      is increasing. Youths who were abused and neglected and in out-of-home care are
      among those at highest risk of acquiring HIV. The concurrence of sexual activity
      and school failures contributes to their high-risk status. Research suggests that
      changing behaviors of troubled youths requires programs that not only include HIV
      related knowledge, attitudes, and skills, but also incentives and skills for
      educational planning that will expand the future life options of these youths.

PMID- 9514000
TI  - Shared experiences: three programs serving HIV-positive youths.
AB  - This article presents the major components of three models of linked psychosocial
      care for HIV-positive youths and youths at high risk for HIV infection: YouthCare
      (Seattle, Washington), TOPS Program (Bridgeport, Connecticut), and Boston HAPPENS
      (Boston, Massachusetts). These models were developed to connect hard-to-reach and
      otherwise marginalized youths to needed services. All sites have successful
      programs that are well integrated with their communities' systems of care for HIV
      positive adolescents. The projects share their program elements, successes, and
      challenges. Practical suggestions are offered to those interested in providing
      and evaluating youth-oriented HIV care programs.

PMID- 9514001
TI  - A place called HOPE: group psychotherapy for adolescents of parents with
      HIV/AIDS.
AB  - Project HOPE is a psychosocial support program for noninfected children of HIV
      positive parents. The challenges of starting and implementing the program's
      psychotherapy group for grieving adolescents, and clinical examples of group
      process and effective interventions in group leadership, are described. Four
      stages in group development are explicated--safety, dependency,
      counterdependency, and independence--paralleling the adolescent separation
      individuation process.

PMID- 9514003
TI  - Investigation of primary and secondary modifiers for the subcritical extraction
      of lovastatin from MEVACOR tablets with carbon dioxide.
AB  - The subcritical fluid extraction of lovastatin from tablet powder mixtures
      prepared in this laboratory and MEVACOR tablets is successfully demonstrated.
      Methanol modifier percentage, additive type (acidic, basic, or neutral), and
      additive concentration on the extraction efficiency are examined. The extraction
      recoveries of lovastatin from MEVACOR tablets are shown to be highly dependent on
      methanol concentration and additive type. Isopropylamine is shown to be the most
      successful additive investigated. An optimized extraction method is developed,
      and lovastatin recoveries of 99.5% were achieved with a relative standard
      deviation of 1.2% from MEVACOR tablets with 15% (v/v) (1.0% [v/v] isopropylamine)
      methanol-modified CO2.

PMID- 9514002
TI  - Simultaneous quantitation of cocaine, opiates, and their metabolites in human
      hair by positive ion chemical ionization gas chromatography-mass spectrometry.
AB  - A sensitive method is developed for the combined extraction of cocaine (COC),
      cocaethylene (CE), benzoylecgonine (BE), ecgonine methyl ester (EME), norcocaine
      (NORCOC), 6-acetylmorphine (6-MAM), codeine (COD), norcodeine (NORCOD), morphine
      (MOR), and normorphine (NORMOR) from human head hair using an enzyme-based
      digestion technique (Protease VIII/DTT/Tris-buffer pH 6.5 at 22 degrees C). After
      pH adjustment to 5.5, the digests are extracted with a solid-phase extraction
      procedure using Bond-Elut Certify columns. The extract residues are evaporated at
      40 degrees C, reconstituted in 20 microL of ethyl acetate, and derivatized with
      the reagents N-methyl-N-trimethylsilylheptafluorobutyramide (MSHFBA), N-methyl
      bis-heptafluorobutyramide (MBHFBA), and N-trimethylsilylimidazole (TMSIM).
      Analyses are performed by positive ion chemical ionization gas chromatography
      mass spectrometry using a DB-1 capillary column. Two injections are performed on
      each extract to optimize sensitivity for all analytes. The assay is capable of
      reliably quantitating 500 pg/mg of all compounds and is linear to 50 ng/mg,
      except for BE, which is linear to 25.0 ng/mg. The method was used to analyze
      human hair samples obtained from cocaine and heroin users. COC, BE, and EME are
      detectable in all samples, whereas NORCOC, CE, COD, 6-MAM, and MOR are detected
      in only some samples. Norcodeine and normorphine are not detected. The assay is
      currently being used to analyze hair samples from a study investigating the
      mechanisms of drug disposition in hair.

PMID- 9514004
TI  - Separation of aromatic acids, DOPA, and methyl-DOPA by capillary electrophoresis
      with dendrimers as buffer additives.
AB  - Polyamidoamine starburst dendrimers with terminal carboxylate groups are used as
      a pseudo-stationary phase in electrokinetic chromatography for separating the
      selected aromatic amino acids phenylalanine, phenylglycine, homophenylalanine,
      and tyrosine and the catecholamines 3-(3,4-dihydroxyphenyl)alanine and 3-(3,4
      dihydroxyphenyl)-2-methylalanine at different pH levels. A significant difference
      in analyte selectivity is observed between dendrimers of different generations
      and at different pH levels. At pH 7.0, the utility of the dendrimers for
      separating these analytes is limited by relatively low selectivity and a noisy
      baseline. However, good separation and selectivity are obtained with low
      generation dendrimers (G0.5 and G1.5) at low pH. Strong association of the solute
      with dendrimers is observed for high generations (G2.5, G3.5, and G5.5).

PMID- 9514005
TI  - Limonoids showing selective toxicity to DNA repair-deficient yeast and other
      constituents of Trichilia emetica.
AB  - Bioactivity-directed fractionation of the MeCOEt extract of Trichilia emetica
      (Meliaceae) resulted in the isolation of the limonoids nymania 1 (1), drageana 4
      (3), trichilin A (4), rohituka 3 (5), and Tr-B (7) and the novel seco-A
      protolimonoid 8. Of these, nymania 1 and Tr-B showed selective inhibitory
      activity toward DNA repair-deficient yeast mutants. The isolation, structure
      elucidation, 13C NMR spectral assignments, and biological activities of these
      compounds are reported.

PMID- 9514006
TI  - Fomitellic acids, triterpenoid inhibitors of eukaryotic DNA polymerases from a
      basidiomycete, Fomitella fraxinea.
AB  - Four new triterpenoid compounds, 1-4, were isolated from the mycelium of a
      basidiomycete, Fomitella fraxinea, and their structures determined by
      spectroscopic analyses. Compounds 1-5 inhibited calf DNA polymerase alpha and rat
      DNA polymerase beta, with respective minimum inhibitory concentration (MIC)
      ranges of 35-75 and 90-130 microM.

PMID- 9514008
TI  - Biosynthesis of ganefromycin: results from blocked mutants and bioconversion
      experiments.
AB  - The biosynthetic pathway of ganefromycin alpha (8) was investigated using blocked
      mutants of Streptomyces lydicus spp. tanzanius, the ganefromycin alpha producer,
      in conjunction with bioconversion experiments with the products of these mutants.
      Compounds 1-7 and 9-15, which are structurally related to ganefromycin alpha,
      were produced by cultures of secretor mutants showing blockage or diminished
      production of 8. These compounds were isolated, characterized, and subjected to
      bioconversion experiments using converter and other secretor mutants. Some of the
      compounds were shown to be products resulting from blocks at various stages in
      the biosynthetics pathway beyond construction of the polyketide skeleton (e.g.,
      furan ring closure, hydroxylation, glycosylation, etc.). Other compounds were not
      bioconverted by biosynthetically capable mutants and were deemed shunt products.
      A mutant's metabolites and bioconverting ability were used to surmise the
      location of the block. A picture of the later sequence of events leading to the
      synthesis of ganefromycin alpha emerged, including C23-hydroxylation, C13a-O
      methylation, C21a-hydroxylation, and C21a-O-glycosylation. Some of the later
      steps in the biosynthetic pathway for ganefromycin alpha are proposed.

PMID- 9514007
TI  - Synthesis and biological activity of esters in the trans-1,2-dihydroxy-1,2
      dihydroacronycine series.
AB  - Permanganate oxidation of acronycine (1) led to keto alcohol 4 which could be
      reduced to trans-1,2-dihydroxy-1,2-dihydroacronycine (3) using NaBH4. Acylation
      of 3 afforded 12, 13, and 14. These esters (12, 13, and 14) were more potent than
      1 when tested against L-1210 cells in vitro. Diacetate 12 was evaluated in vivo
      against murine P-388 leukemia and was markedly active at a dose 16-fold lower
      than acronycine itself. Comparison of these results with those recently obtained
      in the cis-1,2-dihydroxy-1,2-dihydroacronycine series is discussed.

PMID- 9514009
TI  - Isolation and cytotoxic evaluation of marine sponge-derived norterpene peroxides.
AB  - The marine sponge Diacarnus cf. spinopoculum has provided a series of
      norterpenes, including five new compounds (7-11), two new ent-compounds [(-)-1a
      and (+)-1b], and three known compounds (2a, 2b, and 12). Eight of these compounds
      represent additional examples of the muqubilin/sigmosceptrellin classes
      (norsesterterpene peroxides) or the nuapapuin class (norditerpene peroxides).
      Also isolated were dinorditerpenones 11 and 12, which are biosynthetically
      related to the muqubilin/sigmosceptrellin structure classes. In all, 11 compounds
      were evaluated for their cytotoxic properties using a soft agar assay system and
      the NCI's 60 cell-line screen. Compounds without peroxide functionality were
      inactive. Overall, the norsesterterpene peroxides were less selective as
      cytotoxins than norditerpene peroxide analogues. Two compounds, nuapapuin A
      methyl ester (3) and nuapapuin B (7), which were somewhat selective in their
      cytotoxic behavior, were selected for further in vivo evaluation.

PMID- 9514010
TI  - Transtorine, a new quinoline alkaloid from Ephedra transitoria.
AB  - Transtorine (1), a new quinoline alkaloid, isolated from the aerial part of
      Ephedra transitoria by column chromatography, was identified as 4-quinolone-2
      carboxylic acid. The structure was determined by spectroscopic methods.
      Transtorine exhibited growth inhibitory activity against the common bacteria,
      Enterobacter cloacae, Escherichia coli, Pseudomonas aeruginosa, and
      Staphylococcus aureus.

PMID- 9514011
TI  - Microbial transformation of dihydrosarsasapogenin with Mycobacterium sp.
AB  - Microbial transformation of sarsasapogenin (1) with Mycobacterium sp. (NRRL B
      3805) gave 25(S)-neospirost-4-en-3-one (2) as the sole product in 62% yield.
      Incubation of dihydrosarsasapogenin (3) led to the isolation of seven products in
      0.5 (4), 6.6 (5), 5 (6), 16 (7), 1 (8), 1 (9), and 4.5% (10) yields,
      respectively, while 15% of 3 was recovered. Among these products, 8 and 9 were
      C22 steroids, and 10 was a C19 steroid. Isolation of these C19 and C22 steroids
      indicated that this microorganism is capable of cleaving the ether linkage
      between C-16 and C-22 in 3. In addition, 12 alpha-hydroxylation was also observed
      in all these three metabolites.

PMID- 9514012
TI  - Structure and absolute stereochemistry of salvimirzacolide, a new sesterterpene
      from Salvia mirzayanii.
AB  - A new sesterterpene, salvimirzacolide (1), was isolated from the aerial parts of
      Salvia mirzayanii and its structure established by X-ray diffraction analysis.
      Full assignments of 1H- and 13C-NMR spectral data of salvimirzacolide are
      presented.

PMID- 9514013
TI  - Two new cytotoxic compounds from Tapirira guianensis.
AB  - Two new cytotoxic compounds, 2-[10(Z)-heptadecenyl]-1,4-hydroquinone (1) and
      (4R,6R)-dihydroxy-4-[10(Z)-heptadecenyl]-2-cyclohexenone (2) have been isolated
      from a MeOH extract of seeds of Tapirira guianensis. The structures were
      established through spectral analysis of the isolates and their derivatives.

PMID- 9514014
TI  - Destruxin-A4 chlorohydrin, a novel destruxin from fungus OS-F68576: isolation,
      structure determination, and biological activity as an inducer of erythropoietin.
AB  - In the course of screening for small-molecule modulators of erythropoietin gene
      expression, five destruxins were isolated from the fungal culture of OS-F68576.
      The structures were elucidated by extensive 1H and 13C NMR spectroscopy and by
      hydrolytic modification. One compound (destruxin-A4 chlorohydrin, 1) is a novel
      destruxin. All these compounds induced erythropoietin gene expression 5-fold at
      concentration of 0.2-2 microM.

PMID- 9514016
TI  - Cancellation model of pitch perception.
AB  - A model of pitch perception is presented involving an array of delay lines and
      inhibitory gating neurons. In response to a periodic sound, a minimum appears in
      the pattern of outputs of the inhibitory neurons at a lag equal to the period of
      the sound. The position of this minimum is the cue to pitch. The model is similar
      to the autocorrelation model of pitch, multiplication being replaced by an
      operation similar to subtraction, and maxima by minima. The two models account
      for a wide class of pitch phenomena in very much the same way. The principal goal
      of this paper is to demonstrate this fact. Several features of the cancellation
      model may be to its advantage: it is closely related to the operation of harmonic
      cancellation that can account for segregation of concurrent harmonic stimuli, it
      can be generalized to explain the perception of multiple pitches, and it shows a
      greater degree of sensitivity to phase than autocorrelation, which may allow it
      to explain certain phenomena that autocorrelation cannot account for.

PMID- 9514015
TI  - Bioactive pyridoacridine alkaloids from the micronesian sponge Oceanapia sp.
AB  - The Micronesian sponge Oceanapia sp. afforded three pyridoacridine alkaloids: the
      known compounds kuanoniamine C (1) and kuanoniamine D (2), as well as the new N
      deacyl derivative (3) of the kuanoniamines. Compounds 1 and 2 exhibited
      insecticidal activity toward neonate larvae of the polyphagous pest insect
      Spodoptera littoralis (LC50 of 156 and 59 ppm, respectively), when incorporated
      into artificial diet. Both compounds also showed toxicity in the brine shrimp
      lethality test with a LC50 of 37 micrograms/mL (compound 1) and 19 micrograms/mL
      (compound 2), respectively. The N-deacyl derivative did not show any remarkable
      effect in both bioassays. Cytotoxcity of the alkaloids was studied in vitro,
      using two human cell lines. The new derivative (3) appeared to be active in the
      same range of concentrations as kuanoniamine C (1) and D (2). The IC50 of 3 was
      1.2 micrograms/mL toward HeLa cells and 2.0 micrograms/mL toward MONO-MAC 6
      cells. In receptor binding assays compound 2 showed affinity to A1- and A2A
      adenosine receptors with Ki values of 2.94 and 13.7 microM, respectively.
      Compound 1 was less active than compound 2, whereas compound 3 showed no affinity
      toward adenosine receptors. In addition, compounds 1-3 exhibited moderate
      affinity to benzodiazepine binding sites of GABAA receptors.

PMID- 9514017
TI  - Inverse imaging of the breast with a material classification technique.
AB  - In recent publications [Chew et al., IEEE Trans. Blomed. Eng. BME-9, 218-225
      (1990); Borup et al., Ultrason. Imaging 14, 69-85 (1992)] the inverse imaging
      problem has been solved by means of a two-step iterative method. In this paper, a
      third step is introduced for ultrasound imaging of the breast. In this step,
      which is based on statistical pattern recognition, classification of tissue types
      and a priori knowledge of the anatomy of the breast are integrated into the
      iterative method. Use of this material classification technique results in more
      rapid convergence to the inverse solution--approximately 40% fewer iterations are
      required--as well as greater accuracy. In addition, tumors are detected early in
      the reconstruction process. Results for reconstructions of a simple two
      dimensional model of the human breast are presented. These reconstructions are
      extremely accurate when system noise and variations in tissue parameters are not
      too great. However, for the algorithm used, degradation of the reconstructions
      and divergence from the correct solution occur when system noise and variations
      in parameters exceed threshold values. Even in this case, however, tumors are
      still identified within a few iterations.

PMID- 9514018
TI  - Signal processing of the echo signatures returned by submerged shells insonified
      by dolphin "clicks:" active classification.
AB  - A large set of dolphin-emitted acoustic pulses ("echolocation clicks") have been
      examined, which were reflected from various elastic shells that were suspended,
      underwater, 4.5 m in front of the animal in a large test site in Kaneohe Bay,
      Hawaii. A carefully instrumented analog-to-digital system continuously captured
      the emitted clicks and also the returned, backscattered echoes (A/D conversion at
      500 kHz). Using standard conditioning techniques and food reinforces, the dolphin
      is taught to push an underwater paddle when the "correct" target-the one he has
      been trained to identify-is presented to him. He communicates his consistently
      correct identifying choices in this manner. Many echoes returned by three types
      of cylindrical shells in both the time and frequency domains as well as in the
      joint time-frequency (t-f) domain, by means of Wigner-type distributions have
      been examined. It will be shown exactly how specific features observable in these
      displays are directly related to the physical characteristics of the shells. This
      processing takes advantage of certain fundamental resonance principles to show
      which echo features contain information about the size, shape, wall thickness,
      and material composition of both the shell and its filler substance. In the same
      fashion that these resonance features give the identifying characteristics of
      each shell, it is believed they may also give them to the dolphin. These echo
      features may allow him to extract the target properties by inspection without any
      need for computations. It is claimed that this may be the fundamental physical
      explanation of the dolphin's amazing target ID feats, upon which they base their
      recognition choices. This claim may be substantiated by the detailed analysis of
      many typical echoes returned by various shells, when they are interrogated by
      several dolphins. Thus far, this analysis of many echoes from many shells has
      only been carried out for a single dolphin.

PMID- 9514019
TI  - The mammalian auditory hair cell: a simple electric circuit model.
AB  - A model based on the potassium current pathway through the hair cell is used to
      analyze the electrical behavior of mammalian inner and outer hair cells. Without
      taking into account the effects of calcium it is possible to simulate
      experimental results concerning the shape and strength of the receptor potential
      and the frequency dependent ac (alternating current) and dc (direct current)
      components of the receptor current. This model and a simplified form of it are
      utilized to explain: (1) Transduction latencies: that the receptor potential
      follows a stimulating signal with a very short delay, under the assumption of a
      constant number of open K+ channels in the lateral part of the cell membrane. (2)
      Transduction gains: why higher potential changes are measured in inner hair cells
      than in outer hair cells, although the outer hair cells are expected to be
      exposed to higher stereociliary motions: in inner hair cells a decrease in the
      conductance of the basolateral membrane causes higher gain (receptor potential
      increases) and together with an increase of membrane capacitance slower reaction
      (a larger time constant). (3) Transduction channel kinetics: that the shortest
      (0.1 ms) as well as the longest (20 ms) possible open times of the transduction
      channels in the stereocilia have different frequency related effects on the shape
      of the receptor potentials.

PMID- 9514020
TI  - Effectiveness of intermittent and continuous acoustic stimulation in preventing
      noise-induced hearing and hair cell loss.
AB  - Resistance to noise-induced hearing loss (NIHL) was studied in gerbils exposed
      either to intermittent or continuous low-level noise prior to an intense noise.
      Auditory-evoked brainstem response (ABR) thresholds, distortion product
      otoacoustic emissions (DPOAEs), Q10dB values from compound action potential (CAP)
      tuning curves, and outer hair cell (OHC) loss were measured for each group.
      Subjects were exposed to A-weighted noise (octave band noise centered at 2 kHz)
      on an intermittent (80 dB, 6 h/day) or continuous schedule (74 dB, 24 h/day) for
      10 days, allowed to rest in quiet for 2 days, then exposed to intense A-weighted
      noise (107 dB, 24 h/day) for 2 days. A "noise-only" group was exposed only to the
      intense noise. Gerbils exposed in both the "intermittent" and "continuous" groups
      had less (15-30 dB) temporary threshold shift (TTS) than those in the noise-only
      group. In addition, the continuous group had less (10-15 dB) permanent threshold
      shift (PTS) than the other groups. These data suggest that resistance to NIHL is
      evident in both the intermittent and continuous groups when TTS is measured, but
      resistance to PTS is afforded only by the continuous paradigm. Both paradigms
      decreased OHC loss as compared to the noise-only group, with the continuous
      paradigm being most effective. However, neither paradigm conserved DPOAE
      amplitudes or tuning curve Q10dB values relative to the noise-only group.

PMID- 9514021
TI  - Comparison of monaural (CMR) and binaural (BMLD) masking release.
AB  - Release of masking for a sinusoidal signal of 5 kHz masked by a 25-Hz-wide noise
      band centered around 5 kHz was measured. The masking release was provided by a
      second noise band that was comodulated with the on-frequency masker band. For CMR
      configurations the second noise band was centered at 3 kHz and presented to the
      ipsi-lateral or to the contra-lateral ear. For BMLD configurations the second
      band was centered at 5 kHz and presented to the contra-lateral ear. In another
      condition the second noise band also contained the signal presented with such a
      phase that maximal differences in the envelope resulted. For both the CMR and the
      BMLD paradigm, the masking release for the latter condition was larger than for
      the former condition. To assess further the similarity between monaural and
      binaural masking release, a sinusoidal masker and either a noise or a sinusoidal
      signal were used. The data indicate that, at high frequencies, envelope
      correlation may be a valuable cue for CMR as well as for the BMLD.

PMID- 9514022
TI  - Auditory continuity and loudness computation.
AB  - Sequences composed of alternating bursts of different levels with no silences
      separating them can give rise to a perception of a continuous sound upon which is
      superimposed an intermittent stream. These experiments sought to determine how
      the perceived loudness of the intermittent stream depends on the level difference
      between higher-level and lower-level bursts in the sequence in cases in which
      continuity is either heard or not heard. In the main experiment, listeners were
      asked to adjust the level of continuous or intermittent comparison sequences to
      match the loudness of components that appeared to be either continuous or
      intermittent in an alternating-level reference sequence, thus urging them to
      focus on the two-stream percept. Loudness matches of continuous comparison
      stimulus were close to physical levels of the lower-level bursts, whereas matches
      of the intermittent comparison stimulus were well below the physical levels of
      higher-level bursts. These results are discussed in terms of Bregman's [Auditory
      Scene Analysis (MIT, Cambridge, MA, 1990)] "old-plus-new" hypothesis: The
      loudness of the intermittent stream should result from the subtraction of the
      lower level from the higher level under the assumption that the higher-level
      burst represents a simultaneous mixture of sounds including the continuation of
      the lower-level burst. Additional experiments verified that, in the absence of
      the continuity phenomenon, matched levels were very close to the physical levels
      and that matches to fixed-level continuous and intermittent sequences were
      precise. The matching results from the main experiment support predictions of
      neither classical loudness models that do not take auditory organization
      processes into account nor schema-based models that presume a selection of
      information from the higher-level burst that does not affect the perceptual
      content of this burst. The matched levels fell between predictions of models
      based on subtraction of acoustic pressure and acoustic power, but were very
      different from subtraction of loudness measured in sones, suggesting that
      loudness is computed subsequent to auditory organization processes.

PMID- 9514023
TI  - Change in envelope beats as a possible cue in comodulation masking release (CMR).
AB  - The detection advantage associated with masker envelope coherence across
      frequency has typically been described in terms of comparisons of information
      across auditory channels. More recently it has been suggested that analysis of
      the output of a wider initial filter, similar to that suggested for the TMTF, can
      account for the data [B. G. Berg, J. Acoust. Soc. Am. 100, 1013-1023 (1996)].
      This approach suggests that a change in envelope beats could serve as the cue to
      the addition of a pure-tone signal. Data are presented here for the detection of
      a tone added to multiple maskers with coherent envelopes. In one condition a
      change in envelope beats was an accurate potential cue, whereas in others the
      change was too unreliable to serve as an indicator of the presence of the signal.
      All conditions employing maskers with coherent envelopes produced very similar
      thresholds, and all showed improved sensitivity over the case of detecting a
      signal added to a single masker centered on the signal frequency. Results are
      interpreted as evidence that a change in envelope beats does not form the basis
      of detection in CMR.

PMID- 9514024
TI  - Basilar-membrane nonlinearity and the growth of forward masking.
AB  - Forward masking growth functions were measured for pure-tone maskers and signals
      at 2 and 6 kHz as a function of the silent interval between the masker and
      signal. The inclusion of conditions involving short signals and short masker
      signal intervals ensured that a wide range of signal thresholds were recorded. A
      consistent pattern was seen across all the results. When the signal level was
      below about 35 dB SPL the growth of masking was shallow, so that signal threshold
      increased at a much slower rate than masker level. When the signal level exceeded
      this value, the masking function steepened, approaching unity (linear growth) at
      the highest masker and signal levels. The results are inconsistent with an
      explanation for forward-masking growth in terms of saturating neural adaptation.
      Instead the data are well described by a model incorporating a simulation of the
      basilar-membrane response at characteristic frequency (which is almost linear at
      low levels and compressive at higher levels) followed by a sliding intensity
      integrator or temporal window. Taken together with previous results, the findings
      suggest that the principle nonlinearity in temporal masking may be the basilar
      membrane response function, and that subsequent to this the auditory system
      behaves as if it were linear in the intensity domain.

PMID- 9514025
TI  - Binaural detection as a function of interaural correlation and bandwidth of
      masking noise: implications for estimates of spectral resolution.
AB  - Detection thresholds were measured for an antiphasic (S pi) 500-Hz tone masked by
      a binaural noise, as a function of the bandwidth of the noise. Several values of
      interaural correlation of the masking noise were used, ranging from -1 to +1. The
      bandwidth dependence of the thresholds showed a pattern consistent with a 100-Hz
      wide critical band for most values of interaural correlation, even for those
      values which resulted in a considerable binaural release of masking. Only when
      the interaural correlation of the masking noise was very close to, or equal to,
      unity was the bandwidth dependence of the thresholds in accord with an
      approximately 300-Hz-wide "binaural" critical band measured in previous studies.
      Our analysis of the data calls into question the commonly stated notion that
      binaural processing is characterized by a wider critical band than is monaural
      processing.

PMID- 9514026
TI  - A dynamic biomechanical model for neural control of speech production.
AB  - A model of the midsagittal plane motion of the tongue, jaw, hyoid bone, and
      larynx is presented, based on the lambda version of equilibrium point hypothesis.
      The model includes muscle properties and realistic geometrical arrangement of
      muscles, modeled neural inputs and reflexes, and dynamics of soft tissue and bony
      structures. The focus is on the organization of control signals underlying vocal
      tract motions and on the dynamic behavior of articulators. A number of muscle
      synergies or "basic motions" of the system are identified. In particular, it is
      shown that systematic sources of variation in an x-ray data base of midsagittal
      vocal tract motions can be accounted for, at the muscle level, with six
      independent commands, each corresponding to a direction of articulator motion.
      There are two commands for the jaw (corresponding to sagittal plane jaw rotation
      and jaw protrusion), one command controlling larynx height, and three commands
      for the tongue (corresponding to forward and backward motion of the tongue body,
      arching and flattening of the tongue dorsum, and motion of the tongue tip). It is
      suggested that all movements of the system can be approximated as linear
      combinations of such basic motions. In other words, individual movements and
      sequences of movements can be accounted for by a simple additive control model.
      The dynamics of individual commands are also assessed. It is shown that the
      dynamic effects are not neglectable in speechlike movements because of the
      different dynamic behaviors of soft and bony structures.

PMID- 9514027
TI  - Selection and combination of acoustic features for the description of pathologic
      voices.
AB  - The glottal to noise excitation ratio (GNE) is an acoustic measure designed to
      assess the amount of noise in a pulse train generated by the oscillation of the
      vocal folds. So far its properties have only been studied for synthesized
      signals, where it was found to be independent of variations of fundamental
      frequency (jitter) and amplitude (shimmer). On the other hand, other features
      designed for the same purpose like NNE (normalized noise energy) or CHNR
      (cepstrum based harmonics-to-noise ratio) did not show this independence. This
      advantage of the GNE over NNE and CHNR, as well as its general applicability in
      voice quality assessment, is now tested for real speech using a large group of
      pathologic voices (n = 447). A set of four acoustic features is extracted from a
      total of 22 mostly well-known acoustic voice quality measures by correlation
      analysis, mutual information analysis, and principal components analysis. Three
      of these measures are chosen to assess primarily different aspects of signal
      aperiodicity, while the fourth one indicates the noise content of the signal. All
      analysis methods lead to the same feature set that consists of a measure of
      period correlation, jitter, shimmer, and GNE. The two-dimensional projection of
      this set named "hoarseness diagram" allows a graphical illustration of voice
      quality that can be easily interpreted.

PMID- 9514028
TI  - Effects of local speaking rate context on the perception of voice-onset time in
      initial stop consonants.
AB  - This study explored the prediction that local speaking rate context affects the
      perception of voice-onset time (VOT) in initial stop consonants not only for
      ambiguous stimuli at the category boundary, but also for good exemplars from the
      category center [Volaitis and Miller, J. Acoust, Soc. Am. 92, 723-735 (1992)].
      Naturally produced exemplars of the voiceless phonetic category were presented in
      the context of syllables produced at fast or slow speaking rates in a series of
      perceptual tasks, including phonetic discrimination, identification, and goodness
      rating. The results from all three tasks revealed no effects of speaking rate
      context on the perception of VOT in initial stop consonants. Rather, it appears
      that listeners perceive longer VOTs as better exemplars of the voiceless phonetic
      category, irrespective of the rate context. Further, an additional condition, in
      which the instructions and familiarization tasks presented prior to the
      administration of the perceptual tests were similar to those used by Volaitis and
      Miller [J. Acoust. Soc. Am. 92, 723-735 (1992)], revealed that the previous
      results may have been influenced by the experimental design.

PMID- 9514029
TI  - Auditory models of formant frequency discrimination for isolated vowels.
AB  - Thresholds for formant discrimination of female and male vowels are significantly
      elevated by two stimulus factors, increases in formant frequency and fundamental
      frequency [Kewley-Port et al., J. Acoust. Soc. Am. 100, 2462-2470 (1996)]. The
      present analysis systematically examined whether auditory models of vowel sounds,
      including excitation patterns, specific loudness, and a Gammatone filterbank,
      could explain the effects of stimulus parameters on formant thresholds. The goal
      was to determine if an auditory metric could be specified that reduced
      variability observed in the thresholds to a single-valued function across four
      sets of female and male vowels. Based on Sommers and Kewley-Port [J. Acoust. Soc.
      Am. 99, 3770-3781 (1996)], four critical bands around the test formant were
      selected to calculate a metric derived from excitation patterns. A metric derived
      from specific loudness difference (delta Sone) was calculated across the entire
      frequency region. Since analyses of spectra from Gammatone filters gave similar
      results to those derived from excitation patterns, only the 4-ERB (equivalent
      rectangular bandwidth) and delta Sone metrics were analyzed in detail. Three
      criteria were applied to the two auditory metrics to determine if they were
      single-valued functions relative to formant thresholds for female and male
      vowels. Both the 4-ERB and delta Sone metrics met the criteria of reduced slope,
      reduced effect of fundamental frequency, although delta Sone was superior to 4
      ERB in reducing overall variability. Results suggest that the auditory system has
      an inherent nonlinear transformation in which differences in vowel discrimination
      thresholds are almost constant in the internal representation.

PMID- 9514030
TI  - Generation and growth of bilayer defects induced by ultrasound.

PMID- 9514031
TI  - Transfer of radiocaesium in sensitive agricultural environments after the
      Chernobyl fallout in Sweden: III. County of Vasternorrland.
AB  - In 1986 a large number of farms in the Chernobyl-affected area in the county of
      Vasternorrland in northern Sweden were investigated for radiocaesium transfer to
      grass and cereal grain. The soil surface layer (0-5 cm) in 1986 and the crop
      products in 1986-1996 were analysed. The aim was to study the impact of soil and
      crop rotation on sensitivity of 137Cs transfer in a short and long term
      perspective. In the fallout year 1986 the transfer to grass was usually much
      higher than to cereal grain. In this year the transfer to grass was usually much
      higher in the first cut rather than the second cut. The reduction in transfer
      with year was large but variable with site and with crop sequence. Ploughing was
      effective in decreasing the transfer of 137Cs to crops. On arable sites in 1986
      the transfer to cereal straw was larger at late stem elongation (LSE) than at the
      maturing stage. Unexpectedly, there was no clear relationship between transfer of
      137Cs to the crops and any of the soil characteristics. In 1986 the transfer of
      131I to grass and cereals was also investigated on some of the farms. The results
      are compared with the transfer of 137Cs, 2 months after the Chernobyl fallout.

PMID- 9514032
TI  - Comparison of bone lead in pre-Hispanic, 18th century and modern population of
      Tenerife.
AB  - The present study has been performed in order to determine concentrations of lead
      in the bone of 14 individuals who were interred towards the beginning of the 18th
      century at the church 'La Concepcion' (Santa Cruz de Tenerife) of 15 Pre-Hispanic
      individuals of Tenerife and a modern sample for Tenerife, composed of 25
      individuals. We have observed higher bone lead values in the modern population
      than in the ancient one (P = 0.0022), although Pre-Hispanic individuals and those
      of the 18th century showed similar bone lead values.

PMID- 9514033
TI  - Flotation as a remediation technique for heavily polluted dredged material. 1. A
      feasibility study.
AB  - The flotation behaviour of highly polluted dredged material was investigated at
      different pH values by mechanical agitated (Denver) flotation. Up to 80% of
      cadmium, copper, lead and zinc could be concentrated in the froth layer which
      represented only 30% of the total mass. The maximum specificity for heavy metals,
      defined as the concentrating factor, was obtained at pH 8-9. The maximum recovery
      of heavy metals on the other hand was found to be reached at elevated pH values
      (pH 12). In addition the specificity of the flotation process for the transition
      metals could be assigned to their presence as metal sulphides in the dredged
      material. However, the interaction with organic matter is an important factor in
      determining their flotability. The carbonate fraction was irrelevant for the
      flotation behaviour of heavy metals.

PMID- 9514034
TI  - Flotation as a remediation technique for heavily polluted dredged material. 2.
      Characterisation of flotated fractions.
AB  - The particle size distribution and the metal speciation of the heavy metals were
      investigated on dredged sediment and on the fractions obtained by mechanical
      agitated (Denver) flotation. The transition metal ions (cadmium, copper, lead and
      zinc) were flotated specifically independent of the particle size. Particle size
      analysis, EDTA extraction and sequential extracts indicated that during flotation
      a redistribution of metals occurred due to the oxidation of metal sulphides. This
      oxidation process was more pronounced when the flotation was performed at higher
      pH values and resulted in a decrease in flotation specificity.

PMID- 9514036
TI  - Radioactivity measurements on migrating birds (Turdus philomelos) captured in the
      Comunidad Valenciana (Spain).
AB  - The radionuclides 137Cs, 134Cs and 90Sr have been measured in edible tissues and
      bones of migratory birds (song-thrushes, Turdus philomelos) from central and
      northern Europe and captured in the Comunidad Valenciana, Spain in the 1994
      autumn-winter season. Eight years after the Chernobyl accident, extensive
      agricultural lands in Europe are still contaminated and this study shows that
      there was a transfer of radioactive isotopes to the captured migratory song
      thrushes. The whole-body dose commitment to humans consuming these birds is
      estimated.

PMID- 9514035
TI  - Heavy metals in soils and plants of serpentine and industrial sites of Albania.
AB  - Soils developed on serpentine rocks cover a large area in Albania which contains
      large reserves of iron, nickel, chromium and copper and is characterised by a
      high density of mines and metal smelters. This work was conducted to study the
      flora associated with serpentine and former industrial and mining sites in
      Albania. Eight sites were investigated in the south-eastern, central and northern
      parts of the country. Soils were sampled in the Ap horizon and plants were
      collected and identified. Plant material was allowed to dry before being ground.
      Soil and plant samples were analysed for total Ca, Cd, Co, Cr, Cu, Mg, Ni, Pb and
      Zn. Results showed that each site exhibited a high concentration of one or more
      metals. The maximum concentrations of metals in soils dry matter (DM) were 14 mg
      Cd kg-1, 476 mg Co kg-1, 3865 mg Cr kg-1, 1107 mg Cu kg-1, 3579 mg Ni kg-1, 172
      mg Pb kg-1 and 2495 mg Zn kg-1. The Mg/Ca ratio in serpentine soils varied from 1
      to 7.8. A collection of 58 plant species, members of 44 genera and 17 families,
      were collected. Alyssum markgrafii in the north and Alyssum murale in the south
      eastern serpentines had a concentration of 1.26 and 0.85% Ni in DM, respectively.
      In the species Herniaria hirsuta, a serpentine plant, concentrations of 808 mg Ni
      kg-1 and 275 mg Cr kg-1 in DM were recorded. Other taxa (Filago, Inula, Picris,
      Galamintha, Marrubium, Teucrium, Lotus, Ononis and Xeranthemum) from serpentines
      had a high, but not exceptional Ni content. Some species collected on serpentines
      and industrial sites presented rather high concentrations of lead or copper in
      their above-ground parts, probably related to contamination by soil dust.

PMID- 9514037
TI  - An investigation of environmental levels of cadmium and lead in airborne matter
      and surface soils within the locality of a municipal waste incinerator.
AB  - The results of an investigation into the environmental impact of heavy metals in
      the airborne emissions from the Baldovie municipal waste incinerator, Scotland,
      are presented. A sampling network of 1-km grid squares covering a 7 x 9 km area
      was established over the incinerator plant and its surroundings. Surface soil
      core samples were collected from within each 1 km2 and analysed for cadmium and
      lead content. The spatial distribution of lead levels in soils showed a marked
      variation downwind from the Baldovie incinerator in comparison with the
      background level for the area but remained well within the typical range of lead
      in rural, unpolluted, British soils. A comparison of the observed levels of lead
      in local soils, with the predicted downwind long-term ground level lead
      distribution in air indicates that atmospheric emissions of lead originating from
      the Baldovie incinerator directly determine concentrations of lead in soils
      within a radius of 5 km of the incinerator. An empirical relationship between the
      levels of lead in soils and the long-term levels in air was established. In the
      case of cadmium, the spatial distribution of the heavy metal showed neither a
      marked nor extensive contamination of the sampled area around the incinerator and
      remained within the typical range of cadmium levels in rural, unpolluted, British
      soils. The work concludes that atmospheric emissions of lead from the Baldovie
      incinerator significantly determines the local distribution of lead in soils
      within the immediate vicinity of the incinerator.

PMID- 9514038
TI  - The comparative hydrochemistry of two granitic island aquifers: the Isles of
      Scilly, UK and the Hvaler Islands, Norway.
AB  - A comparative study is presented of granitic groundwaters from the Hvaler
      Islands, south-eastern Norway (11 samples) and the Scilly Islands, south-western
      England (10 samples). The islands display similar bulk lithologies (peraluminous
      S-type, U/Th-enriched granites) and land use, but differing glaciation and hence
      weathering histories. The groundwater of both groups bears a strong marine
      signature, although the Hvaler Islands display less marine influence and a
      greater degree of water-rock interaction. The most interesting hydrochemical
      dissimilarities concern the health related trace elements Rn, U and F. These
      display median (and maximum) values of 2510 Bq/l (8520 Bq/l), 15 micrograms/l
      (170 micrograms/l) and 3.3 mg/l (4.4 mg/l), respectively, for Hvaler, compared
      with 140 Bq/l (200 Bq/l), 1.5 micrograms/l (4 micrograms/l) and 0.1 mg/l (0.27
      mg/l) for Scilly. Commonly employed drinking water limits for these parameters
      are 500 Bq/l (Norwegian action level), 20 micrograms/l (Canadian limit) and 1.5
      mg/l. The differences in groundwater contents of these elements between Hvaler
      and Scilly may be ascribed to: (i) differing trace element compositions of the
      granites and fracture mineralisations; (ii) radically differing recent weathering
      histories; and (iii) hydrodynamic factors.

PMID- 9514039
TI  - Elements in the hair of South-east Asian islanders.
AB  - Mercury (Hg), lead (Pb), cadmium (Cd) and copper (Cu) in hair samples from
      Singapore island (85 samples) and two islands off Batam, Indonesia (68 samples)
      were analysed to assess the environmental uptake of elements. Hair samples were
      washed with 0.1% Triton X-100 solution for 20 min in an ultrasonic bath, rinsed
      five times with de-ionized water and air dried. Ten to 20 mg of hair samples were
      digested with 1 ml of ultra-pure concentrated nitric acid in Parr bombs at 120
      degrees C for 2 h. Hair digests were analysed by atomic absorption
      spectrophotometry (AAS). Hg was determined by the cold vapour AAS method and Pb,
      Cd and Cu by the electro-thermal graphite furnace AAS method. For Singapore hair,
      the contents of Cd (in microgram/g) averaged 0.17 (range 0.02-1.81); Cu 13.2
      (range 3.1-70.1); Hg 5.92 (range 1.14-35.52); and Pb 6.74 (range 0.06-107.8). For
      the islands off Batam, Cd was 0.32 (range 0.06-1.80); Cu 21.1 (range 3.8-143.6);
      Hg 5.59 (range 0.78-60.86); and Pb 15.1 (range 0.13-116.6). Statistically
      significant differences in Cd, Pb and Hg contents were observed between the hair
      samples from Singapore and those of the islands off Batam in cumulative logit
      analysis. Hair from Singapore contained more Hg, but less Cd and Pb compared to
      hair from the islands off Batam. For Pb in hair, significant differences were
      also observed between the two islands off Batam (island 1, 18.9; and island 2,
      10.2). These differences in hair metal contents are due to differences in
      community lifestyle (dietary, environmental or occupational intake).

PMID- 9514040
TI  - The effect of sequential extractions of suspended particulate matter on trace
      metal sorption and microbial cell stability.
AB  - Sequential extractions, according to a modified scheme proposed by Tessier et al.
      (Tessier A, Campbell PGC, Bisson M. Sequential extraction procedure for the
      speciation of trace metals. Anal Chem 1979;51:844-851), were performed on
      suspended particulate material (SPM) from the River Mersey, North-West England.
      The resulting solid-phase fractions were spiked with trace levels of Cd and Cu
      and their metal-binding properties were investigated as a function of pH. The
      results indicated that metal binding decreased as the material was successively
      extracted, i.e. the unextracted fraction bound the most metal, while the
      particles which had undergone all of the extractions bound the least metal. This
      effect was attributed to the loss of particle mass during the extractions and to
      the relative metal affinities of the newly exposed surfaces. The exposure of new
      potential binding sites was not an overriding influence on metal binding. The
      strongest binding of Cd appears to be to the nominal manganese oxyhydroxide
      phase, with no measurable binding of Cd by the residual mineral fraction. By
      contrast, the nominal iron and manganese oxyhydroxides, organic material and the
      residual mineral fraction all appear to affect Cu binding significantly. The
      effect of the extractions on the particles was also investigated by transmission
      electron microscopy. Micrographs indicated that the biological material in the
      sample had undergone significant alteration after treatment with the first and
      second extractants (acetate and hydroxylamine, respectively), i.e. before removal
      of the nominal organic fraction. These changes in biological material may affect
      metal binding, complicating the interpretation in terms of simple mineral and
      organic phases.

PMID- 9514041
TI  - The air quality management of the region of Great Casablanca (Morocco). Part 1:
      Atmospheric emission inventory for the year 1992.
AB  - Within the frame of an air quality study of the Great Casablanca Area (GCA), an
      atmospheric emission inventory concerning the major pollutants: SO2; NOx; non
      methane volatile organic compounds (NMVOC); and CO has been realized. This
      inventory has a spatial resolution of 1 km2 and is established for the reference
      year 1992. The area, which covers 2500 km2 includes a region which is very
      sensitive to atmospheric pollution since it is heavily populated and contains up
      to 60% of the industrial activities of Morocco. The results, which include both
      biogenic and anthropogenic sources, show as expected very large emissions of
      pollutants mainly due to the presence of a refinery, several power plants and,
      contrary to the general European situation, the production of NOx is not
      dominated by road traffic.

PMID- 9514042
TI  - Spatial variations of airborne particles in metropolitan Taipei.
AB  - During the summer and fall of 1991, total (TSP) and PM10 measurements were
      conducted at several sites simultaneously to evaluate the spatial variation of
      particle pollution in Taipei. Eighty-four samples were obtained from high-,
      medium- and low-polluted areas of the city. PM10 levels on roadside, sidewalk and
      covered walkways near a main road were 527.8 micrograms/m3, 466 micrograms/m3 and
      477 micrograms/m3, respectively; the concentrations were not significantly
      different horizontally away from the emission sources. The PM10 concentrations on
      the second, seventh and 14th floors of a building were 305.31 micrograms/m3,
      178.3 micrograms/m3 and 168.7 g/m3, respectively; the highest was on the second
      floor, but concentrations did not diminish from the seventh to the 14th floor. In
      addition, PM10 concentrations on the main street, side street and alley of an
      area were 155.3 micrograms/m3, 267.7 micrograms/m3 and 167.1 micrograms/m3,
      respectively; the highest concentration appeared on the side street. Furthermore,
      high fractions of PM10 in TSP mass were 90%, 84% and 79% for the high-, medium-
      and low-polluted areas. The percentages that exceed the US PM10 standard of 150
      micrograms/m3 for the high- and medium-polluted areas were 100% and 71% and their
      exceedance was substantial. Therefore actions to mitigate the emission sources
      need to be fortified.

PMID- 9514043
TI  - New patterns of drinking-water consumption: results of a pilot study.
AB  - A pilot study on water consumption was carried out in the Quebec City region in
      April and May 1996 with 125 people using a 24-h recall plus a 2-day diary.
      Consumption of drinking water via liquid and food was assessed as well as the
      type of water consumed (tap, bottle or filtered water) and place of consumption
      (home or away from home). Most of the people (56%) were drinking some bottled
      water or filtered tap water and 25% of water intake was away from home. Food
      consumption was found to be a non-significant source of drinking-water intake.
      The average water consumption was nearly similar in exclusively tap-water
      consumers and bottled- or filtered-water consumers (1.5 vs. 1.7 l/day, P = 0.29)
      but two-thirds of the consumption in this last group is natural water, while it
      is mixed water in the bottled/filtered-water group. No significant difference in
      amounts consumed were found according to age, but older people drank hot
      beverages and soup more often. The present pilot-study was weakened by a low
      participation rate (14%). Incentive might be necessary to improve participation
      rate and data collection methods must also be simplified. A 24-h recall plus a 1
      day diary seem sufficient and data on consumption could be limited to liquids,
      soups and cereals.

PMID- 9514044
TI  - The effect of lead in tap water on blood lead in children in a smelter town.
AB  - Hettstedt, a city in eastern Germany with a long history of mining and smelting
      of non-ferrous ores, has multiple lead waste deposits and the remains of a former
      lead smelter and a copper-silver smelter. As part of a cross-sectional study, an
      analysis of lead concentrations in drinking water and in blood was undertaken to
      determine the impact of lead in drinking water on the internal burden of lead in
      children. The geometric mean of blood lead levels among children 5-14 years old
      was 35.0 micrograms/l with a 95% confidence interval (C.I.) of 33.4-36.7. The
      geometric mean of lead in the random tap water samples was 0.5 microgram/l (95%
      C.I., 0.5-0.6) and 0.7 microgram/l (95% C.I., 0.6-0.8) in the stagnant tap water
      samples. Blood lead levels were somewhat correlated with the random water
      measures but not the stagnant water measures (random sample: r = 0.12, P = 0.012;
      stagnant sample: r = 0.04, P = 0.396). After adjustment for relevant confounders,
      lead in drinking water (random sample) was not significantly associated with
      blood lead levels. Factors that were significantly associated with blood lead
      included gender, the city area of residence, lead in house dust, regular contact
      with dogs and dirtiness of the child after playing outdoors. Based on this study,
      lead in domestic tap water contributed little to the lead exposure of children in
      the lead contaminated region of Hettstedt.

PMID- 9514046
TI  - Comparative evaluation by semiquantitative reverse transcriptase polymerase chain
      reaction of MDR1, MRP and GSTp gene expression in breast carcinomas.
AB  - Identification and quantitative evaluation of drug resistance markers are
      essential to assess the impact of multidrug resistance (MDR) in clinical
      oncology. The MDR1 gene confers pleiotropic drug resistance in tumour cells, but
      other molecular mechanisms are also involved in drug resistance. In particular,
      the clinical pattern of expression of the other MDR-related genes is unclear and
      their interrelationships are still unknown. Here, we report standardization of
      the procedures used to determine a reliable method of semiquantitative reverse
      transcriptase polymerase chain reaction (RT-PCR) using a standard series of drug
      sensitive and increasingly resistant cell lines to evaluate the expression of
      three MDR-related genes, i.e. MDR1 (multidrug resistance gene 1), MRP (multidrug
      resistance related protein) and GSTp (glutathione-S-transferase p), reported to
      be endogenous standard genes for normalization of mRNAs. A total of 74 breast
      cancer surgical biopsies, obtained before any treatment, were evaluated by this
      method. When compared with classical clinical and laboratory findings, GSTp mRNA
      level was higher in diploid tumours. However, the main finding of our study
      suggests a clear relationship between two of these MDR-related gene expressions,
      namely GSTp and MRP. This finding provides new insight into human breast tumours,
      which may possibly be linked to the glutathione conjugate carrier function of
      MRP. Well defined semiquantitative RT-PCR procedures can therefore constitute a
      powerful tool to investigate MDR phenotype at mRNA levels of different related
      genes in small and precious tumour biopsy specimens.

PMID- 9514047
TI  - The effect of different chemotherapeutic agents on the enrichment of DNA mismatch
      repair-deficient tumour cells.
AB  - Loss of DNA mismatch repair is a common finding in hereditary non-polyposis colon
      cancer as well as in many types of sporadic human tumours. We compared the effect
      of loss of DNA mismatch repair on drug sensitivity as measured by a clonogenic
      assay with its effect on the ability of the same drug to enrich for mismatch
      repair-deficient cells in a proliferating tumour cell population. Mixed
      populations containing 50% DNA mismatch repair-deficient cells constitutively
      expressing green fluorescent protein and 50% mismatch repair-proficient cells
      were exposed to different chemotherapeutic agents. 6-Thioguanine, to which DNA
      mismatch repair-deficient cells are known to be resistant, was included as a
      control. The results in the cytotoxicity assays and in the enrichment experiments
      were concordant. Treatment with either carboplatin, cisplatin, doxorubicin,
      etoposide or 6-thioguanine resulted in enrichment for mismatch repair-deficient
      cells, and clonogenic assays demonstrated resistance to these agents, which
      varied from 1.3- to 4.8-fold. Treatment with melphalan, paclitaxel, perfosfamide
      or tamoxifen failed to enrich for mismatch repair-deficient cells, and no change
      in sensitivity to these agents was detected in the clonogenic assays. These
      results identify the topoisomerase II inhibitors etoposide and doxorubicin as
      additional agents for which loss of DNA mismatch repair causes drug resistance.
      The concordance of the results from the two assay systems validates the
      enrichment assay as a rapid and reliable method for screening for the effect of
      loss of DNA mismatch repair on sensitivity to additional drugs.

PMID- 9514045
TI  - Biological therapy: approaches in colorectal cancer. Strategies to enhance
      carcinoembryonic antigen (CEA) as an immunogenic target.

PMID- 9514049
TI  - K-ras point mutation occurs in the early stage of carcinogenesis in lung cancer.
AB  - In order to determine the topographical distribution of the K-ras codon 12
      mutations in carcinoma and preneoplastic lesions of the lung, selective
      ultraviolet radiation fractionation, as well as microdissection followed by
      polymerase chain reaction-restriction fragment length polymorphism (PCR-RELP),
      was performed. Fourteen of 61 samples amplified (23.0%) had a mutation in the K
      ras codon 12. Of 41 adenocarcinoma, 12 samples (29.3%) had a mutation, whereas
      none of the squamous cell carcinomas had a mutation. One of six large-cell
      carcinomas, one of three carcinoid tumours and none of three other carcinomas had
      a mutation. Direct sequencing revealed that K-ras codon 12 of six samples were
      TGT (Cys), five samples were GTT (Val), two samples were GCT (Ala) and one sample
      was TTT (Phe). A total of 113 lesions of 13 cases covered by dot were amplified
      after UV radiation. All of 74 carcinoma lesions had the mutation, and intratumour
      heterogeneity was not observed. Of 39 non-malignant lesions, one type II cell
      hyperplasia had the mutation, which suggests that the K-ras mutation occurs in
      the early stage of carcinogenesis. The lack of intratumour heterogeneity supports
      the hypothesis.

PMID- 9514048
TI  - NAD(P)H:quinone oxidoreductase 1 reduces the mutagenicity of DNA caused by
      NADPH:P450 reductase-activated metabolites of benzo(a)pyrene quinones.
AB  - The role of microsomal NADPH:cytochrome P450 reductase (P450 reductase) and
      cytosolic NAD(P)H:quinone oxidoreductase 1 (NQO1 or DT-diaphorase) in the
      mutagenicity of benzo(a)pyrene-3,6-quinone (BP-3,6-Q) was studied using supF tRNA
      gene as the mutational target. pUB3 carrying the supF tRNA gene upon
      transformation into the Escherichia coli ES87 cells exhibited a spontaneous
      mutation frequency of 0.62 x 10(-6). Chemical modification of the pUB3 DNA with
      BP-3,6-Q caused a fourfold increase in the mutation frequency, compared with the
      spontaneous mutations. P450 reductase catalysed metabolic activation of BP-3,6-Q
      into reactive products (semiquinone and reactive oxygen species), which caused a
      further increase in the mutation frequency to eightfold over spontaneous
      mutations. Oxygen radical scavengers (SOD and catalase) blocked the P450
      reductase-activated BP-3,6-Q-induced stimulation of mutations. This indicates
      that redox cycling of the semiquinone leading to the generation of reactive
      oxygen species (ROS) was directly responsible for the increased mutation
      frequency of P450 reductase-activated BP-3,6-Q. Analysis of the mutation spectra
      revealed that P450 reductase-activated BP-3,6-Q showed a significantly higher
      preference for frameshift mutations, particularly deletions, compared with the
      spontaneous mutations and the mutations generated by benzo(a)pyrene-7,8
      dihydrodiol-9,10-epoxide (BPDE). The single most frequently observed mutation by
      P450 reductase-activated quinone (semiquinone + ROS) was deletion of a single
      guanosine. Among the base substitutions, G:C --> T:A, G:C --> A:T and G:C --> C:G
      were also noticed. Interestingly, NQO1 competed with P450 reductase and
      specifically prevented the P450 reductase-activated BP-3,6-Q-induced mutations.
      However, BP-hydroquinone (BP-3,6-HQ) generated during the metabolic reduction of
      BP-3,6-Q catalysed by NQO1 caused specific mutations involving the deletion of a
      single cytosine from the DNA sequence 5'-CCCCC-3' in supF tRNA gene at a
      significantly high frequency. A similar cytosine deletion was also observed with
      benzoquinone hydroquinone (HQ), indicating that the deletion of cytosine is
      associated with a hydroquinone class of compounds. These results suggest that:
      (1) quinones and P450 reductase-activated products of quinones (semiquinones and
      ROS) are mutagenic compounds; (2) the mutational spectra of quinones,
      semiquinones and hydroquinones differ from each other with respect to their
      mutational frequency and specificity; (3) NQO1 competes with P450 reductase and
      protects the cells from quinone mutagenicity; and (4) the NQO1 -metabolized
      quinones (hydroquinones), if not eliminated, cause specific mutations that are
      not observed with quinones and P450 reductase-activated quinones (semiquinones
      and ROS).

PMID- 9514050
TI  - Differential expression of matrix metalloproteinases in activated c-ras-Ha
      transfected immortalized human keratinocytes.
AB  - Elevated expression of matrix metalloproteinases (MMPs), a family of secreted
      proteinases that degrade matrix components of basement membranes and connective
      tissues, is strongly correlated with malignant expression in various human
      epithelial cancers and epithelial cancer cell lines. We have tested whether
      elevated levels of MMP expression are also associated with malignant progression
      in human cutaneous squamous cell carcinoma. Constitutive levels of expression of
      steady-state mRNA and of secreted protein encoded by three MMP genes (matrilysin,
      gelatinases A and B) were compared in a unique in vitro model of human skin
      carcinogenesis. This model is composed of the parental immortalized non
      tumorigenic human keratinocyte line (HaCaT), and three activated c-Harvey-ras
      oncogene transfected variants (A-4, I-7 and II-4). Although clone A-4 is non
      tumorigenic, clones I-7 and II-4 exhibit benign and malignant tumorigenic
      phenotypes, respectively, after subcutaneous injection into athymic nude mice.
      Northern blot, Western blot, and zymogram analyses revealed three MMP-specific
      patterns of expression. Constitutive matrilysin mRNA expression was markedly
      increased in the I-7 cells compared with HaCaT, A-4 or II-4 cells. Secreted
      promatrilysin was distinctly increased in the tumorigenic I-7 and II-4 cells
      compared with the non-tumorigenic HaCaT and A-4 cells. Gelatinase A mRNA and
      secreted gelatinase A protein levels were increased in each transfectant compared
      with HaCaT. Both active and inactive forms of gelatinase A were detected.
      Gelatinase B transcripts were not detected, but an EDTA-inhibitable gelatinase
      activity comigrating with gelatinase B was moderately enhanced in both
      tumorigenic variants compared with the non-tumorigenic cells. Because
      promatrilysin and 92-kDa gelatinase secretion were increased in both benign and
      malignant tumorigenic cells, and not related to invasiveness in this model, it is
      concluded that enhanced constitutive expression of these two MMPs is associated
      with acquisition of the tumorigenic phenotype, before acquisition of the
      malignant phenotype.

PMID- 9514051
TI  - The effects of n-6 polyunsaturated fatty acids on the expression of nm-23 in
      human cancer cells.
AB  - This study examined the effect of n-6 polyunsaturated fatty acids (PUFAs) on the
      expression of nm-23, a metastasis-suppressor gene, in two highly invasive human
      cancer cell lines, HT115 and MDA MB 231. A range of n-6 and n-3 PUFAs were
      tested. We report that while linoleic acid and arachidonic acid reduced the
      expression of nm-23-H1, gamma linolenic acid (GLA) and its soluble lithium salt
      markedly increased the expression of the molecules. The stimulation of the
      expression of nm-23 by GLA was seen at both protein and mRNA levels. Up
      regulation of nm-23 was also associated with a reduction of the in vitro
      invasiveness of these cells. It is concluded that gamma linolenic acid (GLA)
      enhances the expression of nm-23. This contributes to the inhibition of the in
      vitro invasion of tumour cells.

PMID- 9514052
TI  - Growth inhibition of DU-145 prostate cancer cells by a Bcl-2 antisense
      oligonucleotide is enhanced by N-(2-hydroxyphenyl)all-trans retinamide.
AB  - Hormonally insensitive prostate cancer is a relatively slow-growing, but usually
      fatal, disease with no long-term treatment options. Transformation of normal
      prostate cells to a malignant phenotype often involves corruption of the
      apoptotic machineries. Bcl-2 protein is one of the key inhibitors of apoptosis
      and is often unregulated in advanced prostate cancer. The prostate cancer cell
      line DU-145 was used as a model of a hormonally insensitive, advanced prostate
      cancer. Cell growth in liquid culture was significantly inhibited by antisense
      Bcl-2 oligonucleotides compared with control sense oligonucleotides; inhibition
      by these oligonucleotides was significantly enhanced on combination with the
      synthetic retinoid N-(2-hydroxyphenyl)all-trans-retinamide (2-HPR).
      Interestingly, growth inhibition occurred in the absence of apoptosis as measured
      using two assay techniques. We hypothesize that in these recalcitrant cells the
      apoptotic pathway is compromised at several levels, and Bcl-2 may play another
      role in promoting cell growth. The use of Bcl-2 antisense oligonucleotides plus 2
      HPR may provide a novel approach to therapy of hormone-resistant prostate cancer.

PMID- 9514053
TI  - 2-(4-Aminophenyl)benzothiazoles: novel agents with selective profiles of in vitro
      anti-tumour activity.
AB  - 2-(4-Aminophenyl)benzothiazole (CJM 126) elicits biphasic growth-inhibitory
      effects against a panel of oestrogen receptor-positive (ER+) and oestrogen
      receptor-negative (ER-) human mammary carcinoma cell lines in vitro, yielding
      IC50 values in the nM range. Substitutions adjacent to the amino group in the 2
      phenyl ring with a halogen atom or methyl group enhance potency in sensitive
      breast lines (pM IC50 values). Transient biphasic dose responses were induced but
      rapidly eradicated after specific drug exposure periods. Two human prostate
      carcinoma cell lines were refractory to the growth-inhibitory properties of 2-(4
      aminophenyl)benzothiazoles; IC50 values > 30 microM were obtained. Potency and
      selectivity were confirmed when compounds were examined in the National Cancer
      Institute's Developmental Therapeutics screen; the spectrum of activity included
      specific ovarian, renal, colon as well as breast carcinoma cell lines. Moreover,
      comparing 6-day and 48-h incubations, the exposure time-dependent nature of the
      biphasic response was corroborated. Differential perturbation of cell cycle
      distribution followed treatment of MCF-7 and MDA 468 cells with substituted 2-(4
      aminophenyl)benzothiazoles. In MDA 468 populations only, accumulation of events
      in G2/M phase was observed. Two MCF-7 cell lines were established with acquired
      resistance to CJM 126 (IC50 values > 20 microM), which exhibit cross-resistance
      to substituted benzothiazoles, but equal sensitivity to tamoxifen and
      doxorubicin. Compared with standard anti-tumour agents evaluated in the National
      Cancer Institute in vitro cell panel, benzothiazoles revealed unique profiles of
      growth inhibition, suggesting a mode(s) of action shared with no known clinically
      active class of chemotherapeutic agents.

PMID- 9514054
TI  - Cytotoxicity of alpha-particle-emitting astatine-211-labelled antibody in tumour
      spheroids: no effect of hyperthermia.
AB  - The high linear energy transfer, alpha-particle-emitting radionuclide astatine
      211 (211At) is of interest for certain therapeutic applications; however, because
      of the 55- to 70-microm path length of its alpha-particles, achieving homogeneous
      tracer distribution is critical. Hyperthermia may enhance the therapeutic
      efficacy of alpha-particle endoradiotherapy if it can improve tracer
      distribution. In this study, we have investigated whether hyperthermia increased
      the cytotoxicity of an 211At-labelled monoclonal antibody (MAb) in tumour
      spheroids with a radius (approximately 100 microm) greater than the range of
      211At alpha-particles. Hyperthermia for 1 h at 42 degrees C was used because this
      treatment itself resulted in no regrowth delay. Radiolabelled chimeric MAb 81C6
      reactive with the extracellular matrix antigen tenascin was added to spheroids
      grown from the D-247 MG human glioma cell line at activity concentrations ranging
      from 0.125 to 250 kBq ml(-1). A significant regrowth delay was observed at 125
      and 250 kBq ml(-1) in both hyperthermia-treated and untreated spheroids. For
      groups receiving hyperthermia, no increase in cytotoxicity was seen compared with
      normothermic controls at any activity concentration. These results and those from
      autoradiographs indicate that hyperthermia at 42 degrees C for 1 h had no
      significant effect on the uptake or distribution of this antitenascin MAb in D
      247 MG spheroids.

PMID- 9514055
TI  - Molecular pathogenesis of sporadic duodenal cancer.
AB  - Whether duodenal adenocarcinoma should be considered as a gastrointestinal or as
      a peripancreatic cancer is a matter of debate, as is the opportunity and type of
      treatment. We investigated 12 such cancers for the genetic anomalies involved in
      the pathogenesis of gastrointestinal malignancies, including (a) those occurring
      in common-type cancers - allelic losses at chromosomes 3p, 5q, 17p and 18q, and
      Ki-ras and p53 alterations; and (b) those characteristic of mutator-phenotype
      cancers - microsatellite instability and TGF-betaRII gene mutations. We found Ki
      ras and p53 mutations in five (42%) and eight cancers (67%), respectively;
      chromosome 3p, 5q, 17p and 18q allelic losses in two of nine (22%), six of ten
      (60%), six of nine (67%) and three of ten (30%) informative cancers,
      respectively. Finally, three cancers (25%) showed widespread microsatellite
      instability and two of them had a TGF-betaRII gene mutation. Our data suggest
      that duodenal cancers may arise from either of the two known pathogenetic
      molecular pathways of gastric and colorectal cancers. The majority of our cases
      were highly aggressive cancers with frequent chromosomal changes and p53
      mutations as observed in the common-type gastrointestinal malignancies, while
      widespread subtle alterations characteristic of mutator-phenotype cancers
      occurred in a minority, which also showed a favourable long-term outcome.

PMID- 9514056
TI  - Characterization of keratin and cell cycle protein expression in cell lines from
      squamous intraepithelial lesions progressing towards a malignant phenotype.
AB  - Two cell lines derived from vaginal intraepithelial neoplasias (VAINs) expressing
      human papillomavirus (HPV) 33 (VAIN I, UT-DEC-1) and 16 (VAIN II, UT-DEC-2) E6-E7
      mRNA were studied in organotypic culture for their keratins and cell cycle
      regulatory proteins in relation to replicative aging. Early-passage UT-DEC-1 and
      UT-DEC-2 cells reproduced epithelial patterns consistent with VAIN. Cells from
      later passages resembled full-thickness intraepithelial neoplasia (UT-DEC-1) and
      microinvasive cancer (UT-DEC-2). The morphological changes were compatible with
      these cell lines' ability for anchorage-independent growth at later passages.
      Simple epithelial keratins were aberrantly expressed in both cell lines. K18
      (absent in normal vaginal keratinocytes) and K17 expression increased in UT-DEC-1
      and UT-DEC-2 cells at late passages. No marked differences in expression of p53
      (wild type in both cell lines), mdm-2 or PCNA were detected in parallel with
      progression. The expression of p21WAF1/cip1 localized mostly to the upper half of
      the epithelium at early passage and was more intense in the HPV 16-positive UT
      DEC-2 cell line expressing K10. In Northern blot analyses, the transcription
      pattern of the HPV 33 E6-E7 of the UT-DEC-1 cell line changed during later
      passages, whereas that of the HPV 16 E6-E7 of the UT-DEC-2 cell line remained
      unaltered. The present characterization of the phenotype of these cell lines
      derived from natural squamous intraepithelial lesions shows an association
      between simple epithelial-type keratin expression and progressive changes in
      growth and morphology, but fails to demonstrate consistent changes in the
      expression of cell cycle regulatory proteins studied in parallel with
      progression.

PMID- 9514058
TI  - Prognostic significance of cyclin E and p53 protein overexpression in carcinoma
      of the renal pelvis and ureter.
AB  - Cyclin E gene alteration in the cell cycle plays an important role in
      carcinogenesis, while p53 protein affects different phase checkpoint pathways by
      activating p21WAF1/CIP1 in the normal cell cycle. We immunohistochemically
      examined the expression of cyclin E and p53 proteins in 121 patients with
      transitional cell carcinoma (TCC) of the renal pelvis and ureter to determine
      their significance for tumour behaviour and patient prognosis. Cyclin E and p53
      immunostaining of the nucleus was observed in 36 tumours (29.8%) and 35 tumours
      (28.9%) respectively. A significant percentage, 69.4% (25 out of 36 tumours), of
      the cyclin E-positive tumours exhibited simultaneous labelling for p53 (P <
      0.05). Mirror-section technique was performed in five selected double-positive
      tumours to identify cancer cells that were nuclei positive for both cyclin E and
      p53. The prevalence of cases simultaneously exhibiting both cyclin E and p53
      immunostaining was higher in the high-grade tumours (P < 0.01) than in the other
      types of tumours. Patients with TCCs coexpressing cyclin E and p53 had a
      significantly poorer prognosis than those expressing neither cyclin E nor p53 (P
      < 0.001). These in vivo findings provide evidence for cyclin E protein
      overexpression in TCCs intimately associated with p53 alteration and suggest that
      simultaneous overexpression of both cyclin E and p53 is related to tumour
      behaviour and poor prognosis.

PMID- 9514057
TI  - p53 mutation is a poor prognostic indicator for survival in patients with
      hepatocellular carcinoma undergoing surgical tumour ablation.
AB  - Forty-two patients with hepatocellular carcinoma (HCC) were resected and their
      tumours were analysed for p53 mutations by GC-clamped denaturing gradient gel
      electrophoresis (DGGE), single-strand conformation polymorphism (SSCP) and gene
      sequencing. All the exons have been analysed in this study. Eight of 12 HCCs with
      cirrhosis due to viral hepatitis and the two patients with sarcomatoid changes
      displayed p53 mutations. In contrast, no mutation was observed in the
      fibrolamellar variant (n = 9), non-cirrhotics (n = 13) and alcoholic cirrhosis (n
      = 6). The mutations observed were in exons 5-8. Two mutations were observed in
      codons 136 and 213 as well as a T insertion between residues 156 and 157 (exon 5)
      and these are reported for the first time in HCC. Likewise, the silent mutation
      polymorphism in codon 213 was noticed in 3 of the 42 patients. Survival analysis
      of these patients after surgery showed the mean and median survival in patients
      with wild-type p53 to be 60 and 43 months respectively. In the group with p53
      mutations, the mean and median survival was 15 and 12 months. The difference was
      statistically significant (P= 0.003).

PMID- 9514059
TI  - Loss of Bcl-2 in invasive breast cancer is associated with high rates of cell
      death, but also with increased proliferative activity.
AB  - Bcl-2 has been demonstrated to inhibit apoptosis in breast cancer cells in vitro,
      and the ratio between Bcl-2 and its proapoptotic homologue Bax seems to be an
      important determinant of cellular sensitivity to induction of apoptosis. However,
      little information is available on the relationship between Bcl-2 and the rate of
      apoptotic and necrotic cell death in breast tumours. From a series of 441
      premenopausal, lymphnode-negative breast cancer patients, a subset of 49 tumours
      was selected in which immunostaining for the 26-kDa isoform of Bcl-2 was either
      absent (n = 23) or very high (n = 26). High expression of Bcl-2 was found to be
      strongly associated with low rates of apoptotic (P < 0.001) and necrotic cell
      death (P < 0.001). The mean value of the apoptotic index was 2.69%+/-1.40% in Bcl
      2-negative tumours and 0.68%+/-1.00% in Bcl-2-positive tumours. Expression of the
      proapoptotic protein Bax correlated neither with Bcl-2 nor with the frequency of
      apoptotic cells. Immunostaining for the antiapoptotic Bcl-2 homologue BcI-X(L)
      correlated with Bcl-2 expression (P < 0.001) but not with apoptosis. High
      proliferation rate and high tumour grade (Bloom-Richardson) were strongly
      associated with absence of Bcl-2 expression (P< 0.001). p53 accumulation was
      associated with absence of Bcl-2 expression and increased apoptotic activity.
      Loss of Bcl-2 expression was strongly correlated with increased apoptotic and
      necrotic cell death, high proliferation rate and high tumour grade, supporting a
      model in which Bcl-2 not only mediates cell death, but also cell division in
      breast cancer tissue, and in which regulation of cell division and cell death are
      tightly linked.

PMID- 9514060
TI  - Allelic imbalance at chromosome 17p13.3 (YNZ22) in breast cancer is independent
      of p53 mutation or p53 overexpression and is associated with poor prognosis at
      medium-term follow-up.
AB  - Molecular and immunohistochemical studies of genetic events on chromosome 17p
      were prospectively compared with conventional clinical and pathological
      parameters and disease behaviour at a minimum of 72 months follow-up. In a series
      of 91 patients with primary operable breast cancer, 37 out of 91 (41%) patients
      had disease relapse and 23 out of 91 (25%) had died during the follow-up period.
      Allelic imbalance at the YNZ22 locus (17p13.3), demonstrated in 33 out of 63
      (52%) informative patients, was significantly associated with disease recurrence
      (P < 0.01, 2 d.f. Cox analysis) and showed a trend towards impaired survival (P =
      0.08, 2 d.f. Cox analysis) after a mean follow-up of 84 months for survivors. By
      contrast, p53 mutation (in 10 out of 60, 17% of cancers), p53 allelic imbalance
      (in 23 out of 56, 41% informative patients), p53 mRNA expression (in 47 out of
      87, 54% patients), p53 mRNA overexpression (in 24 out of 87, 28%) or p53 protein
      expression (detected in 25/76, 32%) were not associated with disease behaviour.
      There was no significant association between allelic imbalance at YNZ22 and any
      abnormality of p53 DNA, RNA or protein. Allelic imbalance at 17p13.3 (YNZ22)
      serves as a marker of poor prognosis in breast cancer. As yet unidentified genes
      on 17p13.3, distinct from and telomeric to p53, are therefore likely to be of
      clinical importance in breast cancer.

PMID- 9514061
TI  - Serum levels of soluble intercellular adhesion molecule-1 (ICAM-1, CD54) in
      patients with non-small-cell lung cancer: correlation with histological
      expression of ICAM-1 and tumour stage.
AB  - The expression of the intercellular adhesion molecule-1 (ICAM-1, CD54) seems to
      have an influence on the metastatic behaviour of tumour cells via immunological
      mechanisms. Recently, a soluble form of ICAM-1 was identified in physiological
      fluids. We analysed the serum levels of sICAM-1 in patients with non-small-cell
      lung cancer (NSCLC) and healthy individuals using a sandwich ELISA technique.
      Sera from 51 patients with NSCLC were tested for sICAM-1 (46 male, five female;
      age 38-81 years, median 64 years), 29 of whom presented with localized and 26
      with metastatic disease. The control group consisted of 40 healthy individuals
      (20 smokers, 20 non-smokers). Immunohistochemical analysis of ICAM-1 in tumour
      cells was performed in 20 cases. Patients with NSCLC had significantly higher
      serum levels of sICAM-1 compared with healthy non-smokers (P = 0.00001) and
      smokers (P= 0.0328). Metastatic disease was associated with higher sICAM-1 than
      localized tumours (P = 0.0013). Only 11 out of 23 patients with localized NSCLC
      had sICAM-1 levels >300 ng ml(-1), compared with 25 out of 28 patients with
      metastatic disease. Histological expression of ICAM-1 was positively correlated
      with serum slCAM-1 (P = 0.0399). No difference was observed between histological
      tumour types with regard to sICAM-1 or NSCLC expression of ICAM-1. In sequential
      analysis (13 patients), rising sICAM-1 levels predicted a short-term fatal
      outcome (P = 0.0054) but, overall, sICAM-1 levels did not correlate with
      prognosis. In the control group, smokers showed significantly higher levels than
      non-smokers (P = 0.0016). In contrast to patients with NSCLC, sICAM-1 in the
      control group was correlated to the leucocyte count (r = 0.580, P = 0.003). In
      conclusion, serum levels of sICAM-1 seem to be associated with tumour burden and
      histological expression of ICAM-1 in patients with NSCLC. However, the (patho-)
      physiological role of ICAM-1 in NSCLC remains to be determined.

PMID- 9514062
TI  - Dose-limiting neurotoxicity in a phase I study of penclomedine (NSC 388720, CRC
      88-04), a synthetic alpha-picoline derivative, administered intravenously.
AB  - 3,5-Dichloro-2,4-dimethoxy-6-(trichloromethyl)pyridine (penclomedine, NSC 338720,
      CRC 88-04) is an alpha-picoline derivative with anti-tumour activity in
      preclinical models. Penclomedine administration by 1-h intravenous infusion on 5
      consecutive days was repeated 3 weekly in the absence of dose-limiting toxicity
      (DLT) or disease progression. Five dose levels were investigated (22.5-340 mg m(
      2) day[-1]). Eight men and eight women were entered, median age 59 years (range
      39-73 years), with good performance status (ECOG 0/1) in 11 patients. A total of
      13 out of 16 patients had received previous chemotherapy. Common toxicity
      criteria grade (CTCg) II vomiting was recorded at all dose levels. Neurotoxicity
      (cerebellar ataxia and dizziness) was the DLT, CTCg III toxicity occurring in
      three out of three patients treated at 340 mg m(-2) day(-1). CTCg III dizziness
      was noted in one out of three patients at 250 mg m(-2) day(-1). Neurotoxicity
      developed during the 1-h infusion and persisted for a variable period (maximum 5
      h) after infusion. Prophylactic antiemetic drugs appeared to reduce associated
      vomiting but did not prevent ataxia. No antiproliferative toxicities were noted
      and no anti-tumour responses were documented. Penclomedine pharmacokinetic
      studies confirmed preclinical evidence of extensive apparent distribution (93 l
      m[-2]) and rapid clearance (41 l h[-1] m[-2]). Purkinje cell loss has been
      identified in preclinical models after intraperitoneal administration (O'Reilly
      et al, 1996a) and further clinical development of penclomedine will focus on oral
      administration.

PMID- 9514063
TI  - Spatial temporal patterns in childhood leukaemia: further evidence for an
      infectious origin. EUROCLUS project.
AB  - The EUROCLUS project included information on residence at diagnosis for 13351
      cases of childhood leukaemia diagnosed in the period 1980-89 in defined
      geographical regions in 17 countries. A formal algorithm permits identification
      of small census areas as containing case excesses. The present analysis examines
      spatial-temporal patterns of the cases (n = 970) within these clustered areas.
      The objectives were, first, to compare these results with those from an analysis
      conducted for UK data for the period 1966-83, and, second, to extend them to
      consider infant leukaemias. A modification of the Knox test investigates, within
      the small areas, temporal overlap between cases in a subgroup of interest at a
      putative critical time and all other cases at any time between birth and
      diagnosis. Critical times were specified in advance as follows: for cases of
      acute lymphoblastic leukaemia aged 2-4 years, the 18-month period preceding
      diagnosis; for cases of total leukaemia aged 5-14 years, 1 year before to 1 year
      after birth; and for infant cases (diagnosed < 1 year), 1 year before to 6 months
      after birth. Each of the analyses found evidence of excess space-time overlap
      compared with that expected; these were 10% (P = 0.005), 15% (P= 0.0002) and 26%
      (P= 0.03) respectively. The results are interpreted in terms of an infectious
      origin of childhood leukaemia.

PMID- 9514064
TI  - Spatial clustering of childhood leukaemia: summary results from the EUROCLUS
      project.
AB  - The interpretation of reports of clusters of childhood leukaemia is difficult,
      first because little is known about the causes of the disease, and second because
      there is insufficient information on whether cases show a generalized tendency to
      cluster geographically. The EUROCLUS project is a European collaborative study
      whose primary objective is to determine whether the residence locations of cases
      at diagnosis show a general tendency towards spatial clustering. The second
      objective is to interpret any patterns observed and, in particular, to see if
      clustering can be explained in terms of either infectious agents or environmental
      hazards as aetiological agents. The spatial distribution of 13351 cases of
      childhood leukaemia diagnosed in 17 countries between 1980 and 1989 has been
      analysed using the Potthoff-Whittinghill method. The overall results show
      statistically significant evidence of clustering of total childhood leukaemia
      within small census areas (P=0.03) but the magnitude of the clustering is small
      (extra-Poisson component of variance (%) = 1.7 with 90% confidence interval 0.2
      3.1). The clustering is most marked in areas that have intermediate population
      density (150-499 persons km[-2]). It cannot be attributed to any specific age
      group at diagnosis or cell type and involves spatial aggregation of cases of
      different ages and cell types. The results indicate that intense clusters are a
      rare phenomenon that merit careful investigation, although aetiological insights
      are more likely to come from investigation of large numbers of cases. We present
      a method for detecting clustering that is simple and readily available to cancer
      registries and similar groups.

PMID- 9514065
TI  - Childhood cancer and paternal employment in agriculture: the role of pesticides.
AB  - Previous studies have suggested that the offspring of men potentially exposed to
      pesticides at work may be at increased risk of kidney cancer (Wilms' tumour),
      brain tumours, Ewing's bone sarcoma and acute leukaemia. This paper examines the
      association between potential occupational exposure of fathers to pesticides and
      offspring's death from cancer in a large national database. Records for 167703
      childhood deaths occurring during 1959-63, 1970-78 and 1979-90 in England and
      Wales have been analysed. Among the offspring of men with potential occupational
      exposure to pesticides there were 5270 deaths, of which 449 were due to cancer.
      Associations were assessed using proportional mortality ratios (PMRs), with
      adjustment for age, year of death and paternal social class. Of the childhood
      cancers previously linked with potential paternal occupational exposure to
      pesticides, the only statistically significant excess was for kidney cancer
      (PMR=1.59, 95% CI=1.18-2.15, based on 42 deaths). Although these results offer
      some support for the suggestion that paternal occupational exposure to pesticides
      may be related to the subsequent development of kidney cancer in offspring, other
      explanations cannot be excluded. In the light of the findings presented here and
      elsewhere, further, more detailed, research into the nature of this relationship
      is warranted.

PMID- 9514066
TI  - The use of videotaped information in cancer genetic counselling: a randomized
      evaluation study.
AB  - A video of introductory information about inherited susceptibility to breast
      cancer was made in consultation with clinicians in four Scottish cancer family
      clinics. One hundred and twenty-eight women, newly referred for breast cancer
      risk counselling were randomized to receive the video before (n = 66) or after (n
      = 62) counselling. Data were collected before randomization at clinic and by
      postal follow-up at 1 month. The Video Before group had shorter consultations
      with the breast surgeon (mean = 11.8 min+/-5.4 vs 14.6+/-7.2 for the Video After
      group). There was no difference between the groups in the accuracy of their risk
      estimate after counselling, although the Video Before group scored higher for
      self-reported (Z= 3.65, d.f. = 1, P < 0.01) and objectively assessed
      understanding (Z= 2.91, d.f. = 1, P < 0.01). At 1 month follow-up, the Video
      Before group were less likely to underestimate their risk estimate (38% vs 18%;
      chi2 = 4.62, d.f. = 1, P< 0.05), but there was then no difference between the
      groups in subjective or objective understanding. Use of the video was not
      associated with increased distress (GHQ, Spielberger State Anxiety) and was
      associated with greater satisfaction with the information given at the clinic.
      This study supports the value of videotape as a method of giving information to
      prepare women for breast cancer risk counselling. Observations of
      misunderstandings and distress emphasize the video should be seen as an aid to,
      not a substitute, for communications at the clinic.

PMID- 9514067
TI  - Determinants of risk of invasive cervical cancer in young women.
AB  - We analysed determinants of risk of cervical cancer in women aged less than 45
      years using data from a case-control study conducted in Italy. Cases were 261
      women aged < 45 years with histologically confirmed invasive cervical cancer.
      Controls were 257 women aged < 45 years, with acute, non-neoplastic conditions,
      judged to be unrelated to any of the known or suspected risk factors for cervical
      cancer. In comparison with women reporting one or no sexual partner, the
      multivariate odds ratio (OR) of cervical cancer was 2.4 (95% confidence interval,
      CI, 1.3-4.6), for women reporting two or more sexual partners, and, in comparison
      with women reporting their first intercourse at 17 years of age or before, the
      multivariate OR was 0.5 (95% CI 0.3-0.9) in women aged > or =23 years at first
      intercourse. The risk of cervical cancer was higher in parous women and increased
      with number of births (OR = 8.1 for three or more births). Among parous women the
      risk tended to increase with later age at last birth; in comparison with parous
      women reporting their last birth before age 25, the OR was 1.9 in those reporting
      their last birth at > or =35 years. No clear association emerged between oral
      contraceptive use, smoking, education, social class and risk of cervical cancer.

PMID- 9514068
TI  - Geographical distribution of birth places of children with cancer in the UK.
AB  - Using birth addresses, we examined the geographical variation in risk for all
      types of childhood cancers in the UK, on a scale corresponding to the 10-km
      squares of the National Grid. The effects of socioeconomic and environmental
      factors, including natural background radiation, were investigated and their
      relative importance assessed using Poisson regression. Data came from a national
      collection of all fatal cancers between 1953 and 1980 in children aged 0-15 years
      and consisted of 9363 children of known place of birth from 12 complete annual
      cohorts born in the period 1953-64. For solid cancers, as well as for leukaemias
      and lymphomas, there was marked variation of cumulative mortality according to
      place of birth. High mortalities were associated with areas characterized as
      having high social class, higher incomes and good housing conditions, but also
      with high population densities (births per hectare). Each of these contrasting
      social indicators operated independently of the other, indicating complex
      determining mechanisms. Mortalities increased with increased radon exposure, and
      the relationship operated independently of the socioeconomic factors. At this
      scale of analysis, we found no increased mortality in industrialized areas. A
      population-mixing infective hypothesis, which postulates high rates of leukaemia
      when highly exposed urban populations are introduced to isolated rural areas, was
      supported by observations of high mortalities in 'growth areas' and New Towns,
      but was not readily reconcilable with the high rates seen in the high-density
      areas. If these correlations do indeed represent an infective mechanism, then the
      outcomes are not limited to malignancies of the immune system alone.

PMID- 9514071
TI  - Whither the global population problem.
AB  - Growth of the human population has been underway for thousands of years and was
      never a problem until recently. It is now expanding exponentially, and today
      global population stands at nearly 6 billion with 97 million being added each
      year. Currently, overpopulation has led to serious social and environmental
      problems such as poverty, overcrowded slums, crime, terrorism, pollution of air
      and water, and depletion of the protective ozone layer. Warnings were sounded,
      but few listened. The enthusiasm once generated for solving the problem of too
      many people was short-lived. The press with puzzling abrogation of its
      responsibility to the public managed to allay all fears of population overgrowth.
      Two U.S. presidents welcomed such growth as a stimulus to economic development.
      Although modern contraceptives are safe, effective, and widely available, more
      are badly needed, but none are in the pipeline. Research is being hampered by
      hostile attitudes and by the high cost in time and money of bringing a new
      contraceptive to an uncertain market with the added threat of litigation. At the
      present rate of growth, the population will double in the next century. This is
      believed to be beyond the carrying capacity of our planet. Corrective measures by
      man or nature need to be undertaken.

PMID- 9514070
TI  - Encrypted morphogens of skeletogenesis: biological errors and pharmacologic
      potentials.
AB  - Bone morphogenetic proteins (BMPs) are members of a class of ancient, highly
      conserved signalling molecules that play major roles in embryonic axis
      determination, organ development, tissue repair, and regeneration throughout the
      animal kingdom. The bone morphogenetic proteins are potent developmental
      morphogens that act in a concentration-dependent manner to specify cell fates in
      developing and regenerating systems. Complementary DNAs have been cloned for
      approximately twenty BMPs, and recombinant proteins have been produced for many
      of these genes. Transgenic and naturally occurring animal models demonstrate a
      wide variety of potential functions for BMP genes during development and tissue
      regeneration, and a wide range of pharmacologic effects are predicted from knock
      out or over-expression of the BMP genes. Fibrodysplasia ossificans progressiva
      (FOP), a rare and devastating genetic disease of ectopic osteogenesis in humans,
      is associated with over-expression of at least one of the BMPs. The BMPs, their
      transmembrane receptors, their intracellular signal transducers, and their
      secreted antagonists hold great promise as pharmacologic agents in modulating a
      vast array of developmental and regenerative pathways in human diseases.

PMID- 9514069
TI  - p53 and angiogenesis in non-small-cell lung cancer.

PMID- 9514072
TI  - Modulation of P-glycoprotein expression by cytochrome P450 3A inducers in male
      and female rat livers.
AB  - A strong overlap between P-glycoprotein (Pgp) and cytochrome P450 3A (CYP3A)
      substrates and modulators has been reported. To test the hypothesis that CYP3A
      and Pgp are coordinately regulated, we examined the effects of known inducers of
      CYP3A (triacetyloleandomycin, rifampicin, dexamethasone, pregnenolone 16alpha
      carbonitrile) on Pgp expression in rat liver. We also investigated the gender
      specific expression of Pgp and compared its response to dexamethasone between
      male and female rats. In male rats, western blot analyses showed that rifampicin
      and dexamethasone caused 50% and 5-fold increases in Pgp levels, respectively.
      RNase protection assays using gene-specific probes for the three Pgp isoforms
      revealed a 3-fold increase in mdr2 mRNA levels after dexamethasone administration
      and a 2-fold increase following rifampicin treatment. Triacetyloleandomycin and
      pregnenolone 16alpha-carbonitrile had no effect on Pgp expression and mRNA
      levels. We also observed that the basal level of Pgp was 40% lower in male rats
      than in females and that mdr2 mRNA levels in male rats were one-half those in
      females. As opposed to the results in male rats, dexamethasone reduced Pgp
      expression by approximately 60% and caused a 30% decrease in mdr2 mRNA levels in
      female rats. Mdr1a was not affected and mdr1b was not detected in female or male
      rats. We conclude that, at the dosage regimen used, CYP3A and Pgp responses to
      CYP3A inducers are regulated independently in rat liver. In addition, this study
      shows that Pgp expression and regulation are gender specific.

PMID- 9514073
TI  - Antiproliferative action of pyrrolobenzoxazepine derivatives in cultured cells:
      absence of correlation with binding to the peripheral-type benzodiazepine binding
      site.
AB  - Three novel peripheral-type benzodiazepine binding site (PBBS) ligands, NF 182,
      213 and 262, along with the classically used PBBS ligands, PK 11195 and Ro5-4864,
      were found to inhibit, at micromolar concentrations and in dose-dependent manner,
      the proliferation of rat C6 glioma and human 1321N1 astrocytoma, without being
      cytotoxic. This antiproliferative effect is mediated by arrest in the G1 phase of
      the cell cycle and does not appear to be mediated by a specific interaction of
      these ligands with the peripheral-type benzodiazepine binding site.

PMID- 9514074
TI  - Alpha- and beta- alkyl-substituted eicosapentaenoic acids: incorporation into
      phospholipids and effects on prostaglandin H synthase and 5-lipoxygenase.
AB  - Alpha-ethyl-, alpha-methyl- and beta-methyl eicosapentaenoic acid (EPA) were
      prepared and their incorporation into cell lipids and effects on eicosanoid
      synthesis compared with EPA and docosahexaenoic acid (DHA). alpha- and beta
      methyl EPA were incorporated into hepatocyte triacylglycerols as efficiently as
      EPA, whereas lesser amounts were found in phospholipids. alpha-ethyl EPA was not
      incorporated into phospholipids but small amounts were detected in
      triacylglycerol. All derivatives inhibited the synthesis of arachidonic acid,
      although less efficiently than EPA and DHA. The derivatives were poor substrates
      of prostaglandin H (PGH) synthase and 5-lipoxygenase, and they all inactivated
      PGH synthase. In isolated platelets, alpha-methyl EPA was a stronger inhibitor of
      TxB2 production than EPA, alpha-ethyl- and beta-methyl EPA. All derivatives were
      stronger inducers of peroxisomal beta-oxidation than EPA and DHA. This increased
      induction probably is a consequence of the blocked mitochondrial beta-oxidation
      of the derivatives.

PMID- 9514075
TI  - Aryl hydrocarbon receptor-associated genes in rat liver: regional coinduction of
      aldehyde dehydrogenase 3 and glutathione transferase Ya.
AB  - The tumor-associated aldehyde dehydrogenase 3 (ALDH3) and the glutathione
      transferase (GST)Ya form are coded by members of the Ah (aryl hydrocarbon)
      battery group of genes activated in the liver by polycyclic hydrocarbons such as
      2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The physiological role of the Ah
      receptor (AHR), its gene-activating mechanism and its endogenous ligands are
      still poorly clarified. We had previously observed that 3-methylcholanthrene
      (3MC) and beta-naphthoflavone (betaNF) induced the AHR-associated CYP1A1/1A2 pair
      in different liver regions, an effect not explained by the acinar distribution of
      the AHR protein. Here, we investigated AHR-associated regional induction by
      comparing the expression patterns of ALDH3 and GSTYa. Analysis of samples from
      periportal and perivenous cell lysates from 3MC-treated animals revealed that
      ALDH3 mRNA, protein and benzaldehyde-NADP associated activity were all confined
      to the perivenous region. In contrast, such regio-specific induction was not seen
      after beta-NF induction. Immunohistochemically, a peculiar mono- or oligocellular
      induction pattern of ALDH3 was seen, consistently surrounding terminal hepatic
      veins after 3MC but mainly in the midzonal region after betaNF. A ligand-specific
      difference in regional induction of GSTYa1 mRNA was also observed: The
      constitutive perivenous dominance was preserved after 3MC while induction by
      betaNF was mainly periportal. A 3MC-betaNF difference was also seen by
      immunohistochemistry and at the GSTYa protein level, in contrast to that of the
      AHR-unassociated GSTYb protein. However, experiments with hepatocytes isolated
      from the periportal or perivenous region to replicate these inducer-specific
      induction responses in vitro were unsuccessful. These data demonstrate that the
      different acinar induction patterns by 3MC and betaNF previously observed for
      CYP1A1 and CYP1A2 are seen also for two other Ah battery genes, GSTYa1 and ALDH3,
      but in a modified, gene-specific form. We hypothesize that unknown protein(s)
      operating in vivo and modifying the Ah-mediated response at the common XRE
      element located upstream of these genes is affected zonespecifically by 3MC and
      betaNF.

PMID- 9514076
TI  - Role of fluidity of membranes on the guanyl nucleotide-dependent binding of
      cholecystokinin-8S to rat brain cortical membranes.
AB  - The binding of [3H]cholecystokinin octapeptide (sulphated) ([3H]CCK-8S), an
      agonist of the cholecystokinin receptors, to rat cortical membranes was fast,
      specific and saturable, with pH optimum at 6.5-7.0. The divalent cations Mg2+ and
      Ca2+ clearly enhanced [3H]CCK-8S binding, whereas the monovalent cations Na+ and
      K+ were inhibitors. Inactivation of the ligand binding ability of these membranes
      was dependent on the incubation temperature and corresponding tau1/2 values were
      11 days at 4 degrees , 12 hr at 21 degrees , 154 min at 30 degrees and 51 min at
      37 degrees , which revealed the apparent activation energy of this process to be
      130+/-4 kJ/mol. Scatchard analysis of the saturation curves of [3H]CCK-8S binding
      was best described by a one site binding model with a Kd = 0.63+/-0.18 nM and a
      maximum binding of 32+/-2 fmol/mg protein. The stable GTP analogue guanosin-5'-O
      (3-thiotriphosphate) (GTPgammaS) decreased the affinity of [3H]CCK-8S binding
      only up to 2-fold without significant influence on maximal binding. Modulation of
      membrane properties by different detergents revealed that only in the case of
      digitonin (0.03-0.04%) did the GTP-dependence of [3H]CCK-8S binding considerably
      increase without significant influence on the ligand binding properties in the
      absence of GTPgammaS. Other detergents studied (sodium cholate, sodium
      deoxycholate, 3-(3-cholamidopropyl)dimethylammonio-1-propanesulfonate (CHAPS),
      sucrose monolaurate, series Triton X and Tween) either had little influence on
      GTP-gammaS-dependence of [3H]CCK-8S binding or inactivated the receptor. Parallel
      studies of fluorescent polarization of diphenylhexatriene (DPH) in rat cortical
      membranes indicated that digitonin was the only detergent which at low
      concentrations caused a rapid increase in membrane fluidity and thereafter
      stabilized it at a certain level. Other detergents studied had only moderate
      influence on membrane fluidity (CHAPS, cholate, deoxycholate) or caused fast and
      continuous increase of membrane fluidity (Triton X-100, Tween 80). These data
      together point to the essential influence of the fluidity of membranes on the
      regulation of the interactions between G proteins and CCK receptors in rat
      cortical membranes. Under standard experimental conditions (temperature lower
      than 30 degrees), the CCK receptor-G protein complex is active for quantitative
      characterization of the receptors, but the membranes are too rigid for natural
      communication and regulation.

PMID- 9514077
TI  - Synergy between two calcium channel blockers, verapamil and fantofarone
      (SR33557), in reversing chloroquine resistance in Plasmodium falciparum.
AB  - This study describes the synergistic interaction of two calcium channel blockers,
      verapamil (VR) and SR33557 or fantofarone (SR), in reversing chloroquine
      resistance in Plasmodium falciparum, the causative agent of human malaria. The
      two calcium channel blockers exhibited an intrinsic antimalarial activity at 10
      and 1 microM for verapamil and fantofarone, respectively. Isobolograms revealed
      that chloroquine and verapamil, and chloroquine and fantofarone, acted
      synergistically against chloroquine-resistant strains of P. falciparum. When used
      at subinhibitory concentrations, verapamil appeared 2 to 3 times more potent than
      fantofarone in reversing chloroquine resistance. Indeed, verapamil completely
      reversed the chloroquine resistance in P. falciparum, while fantofarone did so
      only partially. In the highly chloroquine-resistant strain FcB1, VR and SR acted
      synergistically to reverse CQ resistance, and the concentrations of VR used in
      these combinations could be reduced 10- or 100-fold (e.g. 100 nM and 10 nM) those
      required when this drug was used alone. In the moderately chloroquine-resistant
      strain K1, a combination of VR and SR for CQ resistance reversal allowed us to
      reduce the concentration of these chemosensitizers 1000- and 100-fold,
      respectively. The maximum tolerable plasma level beyond which side-effects
      occurred when using verapamil is 2.5 microM. Thus, the approach described, which
      allowed us to lower the doses of chemosensitizers, could well prevent toxic
      effects in humans and enlighten the advantages of polychemotherapy.

PMID- 9514078
TI  - Nonsteroidal antiinflammatory drug-photosensitized formation of pyrimidine dimer
      in DNA.
AB  - Phototoxic nonsteroidal antiinflammatory drugs (NSAIDs) may induce DNA damage in
      vitro upon irradiation. In this study, we investigated the ability of ketoprofen
      (KP), tiaprofenic acid (Tia), naproxen (NP) and indomethacin (IND) to
      photosensitize the formation of pyrimidine dimers and single strand breaks. Both
      kinds of damage were sought by analyzing DNA-drug mixtures irradiated at 313 nm
      by agarose gel electrophoresis. The formation of pyrimidine dimers was evidenced
      by using endonuclease V from bacteriophage T4 and compared to that induced by
      acetophenone, a well-known photosensitizer of thymine dimerization. Upon
      irradiation of DNA alone, pyrimidine dimers were observed while single strand
      breaks were not detected under our conditions. DNA, in the presence of NSAIDs,
      undergoes single strand breaks, the quantum yield of the DNA cleavage so induced
      (phiC) varying from 5 x 10(-4) for KP to 10(-5) for IND. The formation of dimers
      was only increased in the presence of KP or Tia. The quantum yields of pyrimidine
      dimers formed by photosensitization (phiD) were 2 x 10(-4) for KP and 10(-5) for
      Tia, respectively. The oxygen and concentration dependence of both processes was
      analyzed in the case of KP. In aerated solution, KP-photoinduced cleavage of DNA
      was predominant on the photodimerization process of pyrimidines, whereas in
      deaerated solution the cleavage was decreased and the dimerization increased.
      These results reflect competition between a radical process leading to DNA
      cleavage and a poorly efficient energy transfer between the drug and the
      pyrimidines at the origin of the dimerization process.

PMID- 9514079
TI  - Induction of leukotriene production by bleomycin and asparaginase in mast cells
      in vitro and in patients in vivo.
AB  - Bleomycin and asparaginase are widely used antineoplastic agents which may induce
      allergic or inflammatory side-effects. Mast cells are implicated as effector
      cells in allergic and inflammatory responses. The aim of this study was to
      establish whether bleomycin or asparaginase modulate leukotriene production in
      vitro and in vivo. Leukotriene C4 (LTC4) production by murine bone marrow-derived
      mast cells (BMMC) was determined by radioimmunoassay (RIA). Leukotriene
      production in patients was assessed by determining leukotriene E4 and N-acetyl
      leukotriene E4 in urine by means of combined HPLC and RIA. Bleomycin induced an
      up to 2.1-fold increase in LTC4 production both in unstimulated and in calcium
      ionophore-stimulated mast cells. In 3 of 7 patients treated with bleomycin, a
      greater than 2-fold increase in endogenous leukotriene production was observed.
      This effect was associated with febrile responses and was most pronounced in a
      patient who developed an Adult Respiratory Distress Syndrome (ARDS). Asparaginase
      increased leukotriene production up to 10-fold in stimulated but not in
      unstimulated BMMC. In a patient who developed an anaphylactic reaction after
      treatment with asparaginase, a pronounced increase in urinary leukotriene
      concentration was observed. In contrast to bleomycin or asparaginase, a number of
      other cytostatic agents did not significantly change leukotriene production by
      BMMC. Our data indicate that some of the inflammatory and allergic side-effects
      of bleomycin and asparaginase could be mediated by leukotrienes, a possible
      source of which may be mast cells.

PMID- 9514080
TI  - Heterogeneous forms of adenotin-1 of different subcellular localization.
AB  - The localization of the low-affinity adenosine binding protein adenotin-1 with
      respect to distribution in rat organs and subcellular compartments was
      investigated. Adenotin-1 was characterized by 5'-N-ethylcarboxamido[2,8
      3H]adenosine ([3H]NECA) binding and Western blotting. Cytosolic as well as
      membrane fractions of all tissues contained adenotin-1. Highest levels of
      membrane-bound adenotin-1 were found in the liver (liver > kidney approximately
      spleen approximately lung > forebrain approximately cerebellum > fat heart -
      striated muscle), whereas highest levels of cytosolic adenotin-1 were detected in
      spleen, liver, lung and fat. Subcellular fractions from rat liver were prepared
      by differential and density gradient centrifugation. Like the homologous proteins
      endoplasmin or gp96, adenotin-1 is enriched in the endoplasmic reticulum.
      Cytosolic and membrane-bound adenotin-1 species are pharmacologically distinct,
      because in the liver particulate fraction adenotin-1 showed a more rapid binding
      kinetics, a twofold lower affinity for [3H]NECA (KD 227 nM vs. 105 nM) and a
      sevenfold higher affinity for 2-chloroadenosine than the cytosolic protein (Ki
      1.48 microM vs. 9.25 microM). In rat liver cytosol, two different binding sites
      were found, which differed in [3H]NECA binding kinetics and displayed a
      hundredfold difference in their affinity for 2-chloro-5'-N
      methylcarboxamidoadenosine (Ki 45.8 nM vs. 4.76 microM). The presence of adenotin
      1 in subcellular fractions, as determined by radioligand binding, was confirmed
      by Western blotting. Adenotin-1 was detected as a 98-kDa band in all rat liver
      subcellular fractions, which agrees with the molecular mass determined for the
      purified protein. In the cytosol, a 65-kDa hand was labeled more intensely than
      the 98-kDa band. This additional band probably represents the pharmacologically
      distinct species of adenotin-1 found in the cytosol.

PMID- 9514081
TI  - Inhibition of human class 3 aldehyde dehydrogenase, and sensitization of tumor
      cells that express significant amounts of this enzyme to oxazaphosphorines, by
      chlorpropamide analogues.
AB  - In some cases, acquired as well as constitutive tumor cell resistance to a group
      of otherwise clinically useful antineoplastic agents collectively referred to as
      oxazaphosphorines, e.g. cyclophosphamide and mafosfamide, can be accounted for by
      relatively elevated cellular levels of an enzyme, viz. cytosolic class 3 aldehyde
      dehydrogenase (ALDH-3), that catalyzes their detoxification. Ergo, inhibitors of
      ALDH-3 could be of clinical value since their inclusion in the therapeutic
      protocol would be expected to sensitize such cells to these agents. Identified in
      the present investigation were two chlorpropamide analogues showing promise in
      that regard, viz. (acetyloxy)[(4-chlorophenyl)sulfonyl]carbamic acid 1,1
      dimethylethyl ester (NPI-2) and 4-chloro-N-methoxy-N
      [(propylamino)carbonyl]benzenesulfonamide (API-2). Each inhibited NAD-linked
      benzaldehyde oxidation catalyzed by ALDH-3s purified from human breast
      adenocarcinoma MCF-7/0/CAT cells (IC50 values were 16 and 0.75 microM,
      respectively) and human normal stomach mucosa (IC50 values were 202 and 5 microM,
      respectively). The differential sensitivities of stomach mucosa ALDH-3 and breast
      tumor ALDH-3 to each of the two inhibitors can be viewed as further evidence that
      the latter is a subtle variant of the former. Human class 1 (ALDH-1) and class 2
      (ALDH-2) aldehyde dehydrogenases were much less sensitive to NPI-2; IC50 values
      were >300 microM in each case. API-2, however, did not exhibit a similar degree
      of specificity; IC50 values for ALDH-1 and ALDH-2 were 7.5 and 0.08 microM,
      respectively. Each sensitized MCF-7/0/CAT cells to mafosfamide; the LC90 value
      decreased from >2 mM to 175 and 200 microM, respectively. Thus, the therapeutic
      potential of combining NPI-2 or API-2 with oxazaphosphorines is established.

PMID- 9514082
TI  - Enhancement of gap junctional communication and connexin43 expression by thyroid
      hormones.
AB  - Cells in tissues coordinate their activity by sharing ions, second messengers,
      and small metabolites through clusters of intercellular channels called gap
      junctions. The thyroid hormones 3,3',5-triiodo-L-thyronine (T3) and L-thyroxine
      (T4) are capable of modulating gap junctional communication (GJC) as are 1,25
      dihydroxyvitamin D3, retinoic acid, and other nuclear receptor ligands. T3 and T4
      were found to stimulate GJC in WB-F344 rat liver epithelial cells dose
      dependently at concentrations between 1 nM and 0.1 microM, assayed by the dye
      transfer method using Lucifer Yellow CH. The stimulation of cell-cell
      communication was preceded by an increase in connexin43 mRNA levels and was
      accompanied by an accumulation of connexin43 protein measurable 2 days after
      incubation with these compounds. These observations establish a novel role of
      thyroid hormones in the regulation of gap junctional intercellular communication
      via connexin43 gene expression.

PMID- 9514083
TI  - Effect of angiotensin II on Ca2+ efflux from freshly isolated adult rat
      cardiomyocytes: possible involvement of Na+/Ca2+ exchanger.
AB  - In the present study, we examined the effect of angiotensin II on Ca2+ efflux
      from freshly isolated adult rat cardiomyocytes. Angiotensin II stimulated the
      efflux of 45Ca2+ from the cells in a concentration-dependent manner, at least in
      pharmacological doses of 10(-8) M to 10(-5) M. The 45Ca2+ efflux was inhibited by
      the type 1 angiotensin II receptor antagonist losartan, but not by the type 2
      antagonist PD 123319. Angiotensin II also induced an increase in cytosolic free
      calcium ([Ca2+]i) and inositol trisphosphate formation within the cardiomyocytes.
      Angiotensin II-induced 45Ca2+ efflux and the increase in [Ca2+]i were both
      inhibited by thapsigargin, a specific inhibitor of the sarcoplasmic reticulum
      Ca2+ pump. The 45Ca2+ efflux was not affected by removal of the extracellular
      Ca2+ but was dependent on the presence of extracellular Na+. In addition,
      angiotensin II caused 22Na+ influx into the cells. These results indicate that
      angiotensin II stimulates Na+-dependent 45Ca2+ efflux from freshly isolated adult
      rat cardiomyocytes, probably through its stimulatory effect on the plasma
      membrane type 1 angiotensin II receptors. Angiotensin II-induced increase in
      [Ca2+]i may cause an activation of Na+/Ca2+ exchange which finally results in the
      stimulation of 45Ca2+ efflux from the cells. Since it is reported that Na+/Ca2+
      exchange is important in calcium homeostasis within the cells, angiotensin II may
      play some role in the reduction of intracellular Ca2+ from isolated adult rat
      cardiomyocytes.

PMID- 9514084
TI  - Prolonged depletion of AH receptor without alteration of receptor mRNA levels
      after treatment of cells in culture with 2,3,7,8-tetrachlorodibenzo-p-dioxin.
AB  - Previous experiments have shown that the total cellular content of the AH
      receptor (AHR) drops rapidly after exposure of mouse hepatoma cells (Hepa-1) to
      the potent AHR ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD); within 6 hr
      after treatment, less than 20% of the original cell content of AHR can be
      detected by radioligand binding or by immunoblotting. The goals of our current
      study were to determine the duration of receptor depletion following treatment
      with ligand and to determine if depletion is due to decreased expression of the
      Ahr gene that encodes the AHR. We found that depletion of AHR persisted for at
      least 72 hr after exposure to TCDD. Treatment with 3-methylcholanthrene caused a
      transient drop in total cell AHR, but the AHR levels returned to near
      pretreatment levels within 72 hr after the first exposure. TCDD treatment did not
      alter the levels of AHR mRNA as assessed by reverse transcription-polymerase
      chain reaction or slot blot assays. Thus, the decrease in AHR protein cannot be
      attributed to depression of transcription of the Ahr gene by TCDD. TCDD treatment
      did not alter the levels of the dimerization partner of the AHR, the AH receptor
      nuclear translocator protein (ARNT), or ARNT mRNA. In the presence of TCDD, both
      the AHR and the ARNT protein can be maintained at high levels in the nucleus if
      transcription is inhibited with actinomycin-D. In the absence of actinomycin-D,
      the AHR protein was lost rapidly, but the ARNT protein level in the cell was
      maintained. Together, these results suggest that the AHR protein is degraded
      through a selective mechanism that spares the ARNT protein and that the
      degradation pathway involves a protein that itself has a short half-life.

PMID- 9514085
TI  - Involvement of Src in the vitamin D signaling in human keratinocytes.
AB  - 1,25-dihydroxyvitamin D3 (VD) is a modulator of growth and differentiation of
      many cell types, including keratinocytes. We have recently shown in cultured
      keratinocytes that VD induces tyrosine phosphorylation of proteins involved in
      signal transduction, such as Shc. In an attempt to identify VD-responsive
      tyrosine kinases, we studied the effects of VD on the activity of the nonreceptor
      tyrosine kinase Src. Although VD did not stimulate Src activity in keratinocytes
      cultured in standard media containing 0.15 mM calcium, preincubation of the cells
      with 1.8 mM Ca2+ caused a rapid activation of Src in response to VD (10(-8)-10(
      7) M). Elevation of calcium concentration alone caused an increase in Src
      activity as well, but the peak of Src activity was delayed (60 min vs. 15 min)
      and approximately 2-fold lower in comparison with VD-treated cells. VD treatment
      also induced tyrosine dephosphorylation of Src and a formation of an Src-Shc-Grb2
      complex. Taken together, these findings imply that Src is involved in VD
      signaling in keratinocytes.

PMID- 9514086
TI  - Hexahydrocolupulone and its antitumor cell proliferation activity in vitro.
AB  - The purpose of this study was to evaluate the ability of hexahydrocolupulone
      (HHC) to inhibit the growth of tumor cells in vitro and to investigate the
      potential mechanism(s) involved. HHC was demonstrated to have a wide spectrum of
      activity against a number of established human tumor cell lines, including some
      exhibiting drug resistance. Culturing human breast adenocarcinoma (MCF-7) cells
      in the presence of HHC for 18 hr resulted in a significant decrease in the
      incorporation of [3H]uridine and [3H]leucine into RNA and protein, respectively.
      MCF-7 cells cultured in the presence of 1.5 microM HHC for 48 hr demonstrated an
      increase in the amount of cells detected in G0/G1 and a decrease in the amount of
      cells detected in S phase. In contrast, treatment with 25 microM HHC decreased
      the amount of cells detected in G0/G1 and increased the amount of cells detected
      in S phase. HHC did not cause single-stranded or double-stranded DNA breaks,
      interfere with topoisomerase function, or generate free radicals. Mice injected
      intraperitoneally for 5 consecutive days with HHC to a final in vivo blood
      concentration of 200 microM survived and showed no obvious signs of toxicity.
      Mass spectroscopy analysis, crystal generation, and structure elucidation
      confirmed HHC purity. Consequently, all activity observed can be attributed to
      HHC, a metabolite, and/or a combination thereof. These data suggest that HHC
      inhibits tumor cell proliferation in vitro via a mechanism(s) that may involve
      effects on macromolecular synthesis, precursor metabolism/transport, and/or the
      cell cycle or cell cycle-dependent pathway(s).

PMID- 9514087
TI  - Effect of chronic ethanol exposure on mouse brain arachidonic acid specific
      phospholipase A2.
AB  - The enzyme phospholipase A2 (PLA2), which catalyzes the hydrolysis of an ester
      bond at the sn-2 position of 1,2-sn-diacylglycerols, has been suggested to play
      an important role in regulating cellular functions. Although ethanol (EtOH)
      induced activation of PLA2 activity was reported previously by us in mouse brain
      (Hungund et al., Neurochem Int 25: 321-325, 1994), its subcellular localization
      and biochemical properties have not been investigated. Therefore, in the present
      study, we examined the subcellular localization and characterization of EtOH
      activated PLA2 activity in mouse brain. The results indicated that EtOH treatment
      decreased the specific activity of PLA2 for the first 48 hr, and then the
      activity increased and reached a peak level in both cytosol (1.6-fold) and
      membrane (1.7-fold) fractions at 96 hr of exposure. Specific activity was found
      to be higher in the membrane fraction than in the cytosol. Using differential
      density gradient centrifugation, subcellular localization of the membrane
      associated PLA2 revealed that most of the EtOH-activated PLA2 specific activity
      was associated with the synaptic membrane (44%) followed by the nuclear membrane
      (13%). No significant increase in the PLA2 specific activity of mitochondrial and
      microsomal membranes was observed. No activity was detected in the myelin
      membrane. PLA2 specific activity of membranes from control and EtOH-exposed mouse
      brain exhibited preference for arachidonic acid over linoleic acid at the sn-2
      position of glycero-3-phosphocholine (PC). No detectable PLA2 specific activity
      was found when PC containing oleic acid at the sn-2 position was used as a
      substrate. The present results also indicated that the PLA2 specific activity of
      membrane from control and EtOH-exposed mouse brain was insensitive to
      dithiothreitol, strongly stimulated by Ca2+, enhanced by glycerol, and inhibited
      by the cytosolic PLA2 (cPLA2) inhibitor methyl arachidonyl fluorophosphonate with
      an IC50 value of 3.33 microM. In summary, results suggest that the properties of
      EtOH-activated PLA2 activity found in mouse brain membrane fraction are similar
      to those of cPLA2 found in variety of cells, including mammalian brain.

PMID- 9514088
TI  - Inhibition of the membrane translocation and activation of protein kinase C, and
      potentiation of doxorubicin-induced apoptosis of hepatocellular carcinoma cells
      by tamoxifen.
AB  - Hepatocellular carcinoma (HCC) is characterized by high drug resistance to
      currently available chemotherapeutic agents. In a prospective clinical study, we
      have demonstrated that high-dose tamoxifen significantly enhanced the therapeutic
      efficacy of doxorubicin in patients with far-advanced HCC. In a search for a
      possible mechanism, we found that tamoxifen at a clinically achievable
      concentration (2.5 microM) significantly enhanced doxorubicin-induced
      cytotoxicity and apoptosis of Hep-3B cells, a multidrug resistance (MDR)-1
      expressing HCC cell line. This synergistic cytotoxic effect of tamoxifen, at this
      concentration, however, was not mediated by MDR inhibition. Instead, as evidenced
      by both western blot and immunofluorescence studies, tamoxifen inhibited the
      cytoplasmic-membrane translocation of protein kinase C (PKC)-alpha. 12-O
      Tetradecanoylphorbol-13-acetate (TPA) restored the membrane translocation of PKC
      alpha and abrogated the synergistic cytotoxicity of tamoxifen. We also showed
      that tamoxifen, at this concentration, did not directly affect the enzyme
      activity of PKC. Further, membrane translocation of other membrane-bound
      proteins, such as Ras protein, was similarly inhibited by tamoxifen, but could
      not be restored by the addition of TPA. Together, these data suggested that
      tamoxifen may act on the cytoplasmic membrane, and thereby inhibit PKC-alpha
      translocation to the membrane where it is activated. We hypothesize that high
      dose tamoxifen may be an effective modulator of doxorubicin in the treatment of
      HCC, and suggest that biochemical modulation of PKC as a measure to improve
      systemic chemotherapy for HCC deserves further investigation.

PMID- 9514089
TI  - Stimulation of the intracellular portion of the human insulin receptor by the
      antidiabetic drug metformin.
AB  - Our prior work suggested that the antidiabetic metformin must enter the cell to
      act and that the drug stimulates tyrosine kinase activity. We now report that
      therapeutic concentrations (approximately 1 microg/mL) of metformin stimulated
      the tyrosine kinase activity of the intracellular portion of the beta-subunit of
      the human insulin receptor (IPbetaIRK), the intracellular portion of the
      epidermal growth factor receptor and pp60-src, but not cAMP-dependent protein
      kinase. A derivative of metformin unable to lower glucose was ineffective in
      stimulating IPbetaIRK. Two derivatives more effective than metformin in patients
      were also more effective than metformin in stimulating IPbetaIRK. Higher levels
      (10-100 microg/mL) of metformin or methylglyoxyl bis(guanylhydrazone) inhibited
      the tyrosine kinases, and this inhibition may be responsible for the ability of
      these two drugs to block cell proliferation.

PMID- 9514090
TI  - Studies on inhibitors of mammalian DNA polymerase alpha and beta: sulfolipids
      from a pteridophyte, Athyrium niponicum.
AB  - Three sulfolipid compounds, 1, 2, and 3, have been isolated from a higher plant,
      a pteridophyte, Athyrium niponicum, as potent inhibitors of the activities of
      calf DNA polymerase alpha and rat DNA polymerase beta. The inhibition by the
      sulfolipids was concentration dependent, and almost complete inhibition of DNA
      polymerase alpha and DNA polymerase beta was achieved at 6 and 8 microg/mL,
      respectively. The compounds did not influence the activities of calf thymus
      terminal deoxynucleotidyl transferase, prokaryotic DNA polymerases such as the
      Klenow fragment of DNA polymerase I, T4 DNA polymerase and Taq polymerase, the
      DNA metabolic enzyme DNase I, and even a DNA polymerase from a higher plant,
      cauliflower. Similarly, the compounds did not inhibit the activity of the human
      immunodeficiency virus type 1 reverse transcriptase. The kinetic studies of the
      compounds showed that DNA polymerase alpha was inhibited non-competitively with
      respect to the DNA template and substrate, whereas DNA polymerase beta was
      inhibited competitively with both the DNA template and substrate. The binding to
      DNA polymerase beta could be stopped with non-ionic detergent, but the binding to
      DNA polymerase alpha could not.

PMID- 9514091
TI  - Association of fibroblastoid features with the invasive phenotype in human
      bronchial cancer cell lines.
AB  - The acquisition of a metastatic phenotype by epithelial cells implicates a series
      of changes altering their differentiation, their overall behavior and morphology.
      In the present study, we have examined the relationships between the cellular
      morphology, E-cadherin expression, matrix metalloproteinases expression and in
      vitro invasive properties in two human bronchial immortalized cell lines. The
      (16HBE14o-) cell line which did not show any invasive abilities in the Boyden
      chamber assay displayed a typical epithelial morphology in monolayer, expressed
      high levels of E-cadherin and synthesized neither MMP-2 and MT1-MMP nor vimentin.
      In contrast, the BZR cell line which was highly invasive displayed a more
      elongated phenotype in monolayer, did not produce E-cadherin but expressed
      vimentin, MMP-2 and MT1-MMP. Our data therefore suggest that the metastatic
      progression of broncho-pulmonary cancer cells results in a cellular
      dedifferentiation and the gain of some mesenchymal attributes (loss of E-cadherin
      and expression of vimentin) associated with enhanced degradative properties
      (expression of metalloproteinases).

PMID- 9514092
TI  - Elevated levels of annexin I protein in vitro and in vivo in rat and human
      mammary adenocarcinoma.
AB  - Annexin I is a phospholipid and actin binding protein which may play a role in
      signal transduction to the cytoskeleton. Previous work reported the differential
      expression of annexin I mRNA among rat adenocarcinoma cell lines of various
      metastatic potential (MTLn3, MTLn2, MTC.4: highest to lowest, respectively)
      (Pencil et al. 1993, Breast Cancer Res Treat, 25, 165-74). This relationship has
      been extended to the protein level in in vitro cultures using Western blotting
      and flow cytometry. Annexin I protein levels in MTLn3 cells are 3- to 5-fold
      higher than in MTC.4 cells. The weakly metastatic cell line MTLn2 shows levels
      1.5- to 2.5-fold higher than MTC.4. In vivo tumors were produced by injecting 1 x
      10(6) cells into mammary fat pads of syngeneic rats and necropsies were performed
      40 days later. Semiquantitative immunohistochemical color image analysis was
      performed using a polyclonal rat annexin I specific antibody. Annexin I protein
      expression was highest in lung metastases of MTLn3, at 8-fold the levels observed
      in the MTC.4 primary tumors. MTLn3 cells in the primary tumor had an annexin I
      specific optical density 3-fold higher than that of cells in the MTC.4 primary
      tumor. MTLn2 primary tumors had an annexin I specific optical density 1.5-fold
      higher than MTC.4. A proportion of human mammary adenocarcinomas also have
      positive annexin I immunoreactivity, often with more uniform annexin I staining
      in the lymph node metastases. These results suggest that there may be survival
      advantages for nascent metastatic cells with high annexin I levels.

PMID- 9514095
TI  - Vaccination with B7-1+ tumor and anti-adhesion therapy with RGD pseudo-peptide
      (FC-336) efficiently induce anti-metastatic effect.
AB  - We have previously shown that expression of costimulatory ligand B7-1 on MHC
      class I+ tumor cells (B16-BL6 melanoma) resulted in marked reduction of lung
      metastasis caused by i.v. injection into immunocompetent syngeneic mice and led
      to induction of immunity to the challenge by the parental B7-1 negative tumor.
      Here we investigated the effectiveness of irradiated B7-1 transfected tumor cells
      as a vaccine on established tumor metastasis and whether or not expression of B7
      1 molecule on tumor cells in combination with administration of anti-adhesion
      peptide FC-336 can augment the antimetastatic efficacy. Immunization with X
      irradiated B7-1 transfectants after i.v. injection of B7-1- parental B16-BL6
      cells was effective in inhibiting lung metastasis. We also found that vaccination
      with irradiated B7-1 transfectants after excision of primary tumor on day 21
      resulted in significant inhibition of spontaneous lung metastasis by intrafootpad
      injection of viable parental B16-BL6 melanoma, as compared with the untreated
      control. However, immunizing twice with mock transfectants did not affect
      inhibition of spontaneous lung metastasis of wild-type tumors. On the other hand,
      multiple administration of a pseudo-peptide of RGD sequence (FC-336) after tumor
      inoculation inhibited spontaneous lung metastasis through the interference of
      tumor invasion, migration and adhesion. Combined treatment of B7-1 transfected
      tumor vaccine and anti-adhesive therapy with FC-336 led to the augmentation of
      the antimetastatic effect in both experimental and spontaneous metastasis models,
      as compared with either treatment alone. B7-1- and FC-336-mediated inhibition of
      tumor metastasis may be mediated by different mechanisms at various steps of
      metastasis, based on the regulation (promotion or inhibition) of tumor
      interaction with host cells and components.

PMID- 9514094
TI  - Molecular analysis of two mammary carcinoma cell lines at the transcriptional
      level as a model system for progression of breast cancer.
AB  - As a model system for the identification of genes involved in the progression of
      human breast cancer, differential gene expression in cell lines MCF-7 and MCF
      7ADR was investigated. The latter cell line is derived from the former. Cell line
      MCF-7 is estrogen receptor-positive, vimentin-negative and uninvasive in the
      Matrigel outgrowth assay and in the nude mouse, while MCF-7ADR is estrogen
      receptor-negative, hormone-resistant, vimentin-positive, invasive in the Matrigel
      outgrowth assay and in the nude mouse and resistant to adriamycin due to
      overexpression of glycoprotein gp170. We have shown that tumor progression in
      this model system is mediated by transcriptional regulation of mitochondria
      related genes, proteases, transmembrane receptors and cell cycle-related gene
      proteins. Among the genes differentially regulated at the transcriptional level
      in the cell lines MCF-7 and MCF-7ADR are a new mitochondrial transcript,
      mitochondrial creatine kinase, matrix metalloproteinase-1, stromelysin-3,
      urokinase and its receptor, tissue factor, E-cadherin, epidermal growth factor
      receptor, transmembrane proteins Mat-8 and progression associated protein (PAP),
      cyclin E, cyclin-dependent kinase-2 and cell cycle inhibitory proteins p16, p21
      and p27.

PMID- 9514093
TI  - Inhibition of lung colonisation of a mouse mammary carcinoma by therapeutic
      vaccination with interferon-alpha gene-transduced tumor cells.
AB  - A spontaneously metastatic murine mammary adenocarcinoma, TSA, has been
      transduced with the gene for interferon alpha1 (IFN-alpha). Transfectants were
      used for the immunotherapy of mice bearing lung colonies induced by the
      intravenous inoculation of non-transduced parental cells. A significant reduction
      in the number of tumor colonies was obtained when repeated subcutaneous
      administrations of mitomycin C-blocked transfectant cells were given, commencing
      3 days after an intravenous challenge with TSA cells. Intraperitoneal vaccination
      induced a stronger anti-tumor response than subcutaneous vaccination, and the
      proportion of tumor-free mice reached 50%. The potency of IFN-alpha transfectants
      was similar to that of IFN-gamma transfectants previously obtained from TSA.
      Admixture of IFN-alpha and IFN-gamma transfectant cells in the same vaccine did
      not increase the curative effect over that of single vaccines. In nude mice
      vaccination with IFN-alpha or IFN-gamma transfectants did not lead to a reduction
      in the number of lung colonies, indicating that an intact T cell response was
      required for the therapeutic effect observed in immunocompetent mice.

PMID- 9514096
TI  - Lattices of type I collagen select invasive variants of K-ras oncogene
      transfected NIH3T3 with less cellular fibronectin.
AB  - A clone of NIH3T3 transformant (H3) can yield subcutaneous tumors and
      experimental pulmonary metastasis in nude mice. Compared to H3 in culture, the
      cells after in vivo tumor growth (H3-N) acquired enhanced tumorigenicity and
      metastatic ability. Also, indirect immunofluorescence revealed that cellular
      fibronectin (c-FN) of H3-N was decreased remarkably. We have studied the
      interactions between H3 and extracellular matrices to elucidate these phenomena.
      In the present study, we observed the effect of NIH3T3, H3, and H3-N cultured in
      type I collagen gel. Morphologically in the collagen gel, NIH3T3 assumed an
      extensive elongated fiber-like shape, H3 assumed a moderately elongated shape,
      and H3-N assumed a round or spindle shape with short pseudopodia. Compared to
      conventional cultures on dishes, cell proliferation of all three types was
      suppressed in collagen gel, but the degree of the suppression was least in H3-N.
      As a result, H3-N grew fastest in collagen gel. The variants which acquired
      growth advantage in the subcutaneum of mice also kept it in collagen gel. H3
      cells were cultured in type I collagen gel for 4 weeks, a period comparable to
      that of tumor formation in nude mice. The cells after this long-term culture (H3
      C) acquired enhanced tumorigenicity and metastatic ability nearly equal to that
      of H3-N. FACS analysis revealed that the c-FN of H3-C had decreased to a value
      comparable to that of H3-N. This means that type I collagen gel as well as
      subcutaneous tissues could select variants of H3 with less c-FN through
      proliferation. Moreover, it is suspected that lattices of type I collagen
      regulate cell proliferation of fibroblast via c-FN.

PMID- 9514097
TI  - Heterogeneous suppression of experimentally induced colon cancer metastasis in
      rat liver lobes by inhibition of extracellular cathepsin B.
AB  - Metastatic rat colon cancer cells but not normal rat hepatocytes showed activity
      of cathepsin B on their plasma membranes. Activity was visualized in living cells
      with a new fluorogenic substrate, [Z-Arg]2-cresyl violet, and confocal
      microscopy. When these cancer cells were injected into the portal vein of rats,
      the animals developed tumors in the liver in a heterogeneous fashion. Three- to
      four-fold more tumors were found in the small caudate lobe than in the other
      three large lobes of the liver. Oral treatment with a selective water-soluble
      inhibitor of extracellular cathepsin B, Mu-Phe-homoPhe-fluoromethylketone,
      resulted in 60% reduction of the number of tumors and 80% reduction of the volume
      of tumors in the three large lobes whereas tumor development was not affected in
      the small caudate lobe. This study supports the conclusions that (a)
      extracellular cathepsin B plays a crucial but complex role in liver colonisation
      by rat colon carcinoma cells in vivo, (b) its selective inhibition suppresses
      tumor growth heterogeneously in the liver and (c) the caudate lobe of the liver
      is a relatively large risk factor for tumor development.

PMID- 9514099
TI  - Enhanced metastasis of B16 melanoma cells by unexpected elevated expression of
      the metastasis-associated TI-241 (LRF-1-, Jun-Fos-related) gene treated with
      antisense oligonucleotide.
AB  - B16-F10 is a B16 mouse melanoma subline that preferentially metastasizes to the
      lung following intravenous injection. Previously we isolated TI-241 (LRF-1
      homologue related to Jun-Fos) gene that was expressed higher in the high
      metastatic clone B16-F10 than the low metastatic clone F1. Transfection of TI-241
      into F1 converted it into a high-metastatic cell. We studied the effect of
      antisense oligonucleotide designed to reduce the expression of TI-241 in B16-F10
      cells, and observed an unexpected increase in the TI-241 level. The increase in
      the expression was maximal at 30 h, then it decreased during further culture with
      or without TI-241 antisense oligonucleotide. This increased TI-241 expression by
      antisense oligonucleotide was also observed in B16-F1 cells whereas sense
      oligonucleotide did not affect the expression. B16-F10 cells cultured with TI-241
      antisense oligonucleotide showed enhanced experimental metastatic potential to
      the mouse lungs compared with untreated B16-F10 and B16-F10 cultured with TI-241
      sense oligonucleotide.

PMID- 9514098
TI  - Tumor cell contact mediated transcriptional activation of the fibroblast matrix
      metalloproteinase-9 gene: involvement of multiple transcription factors including
      Ets and an alternating purine-pyrimidine repeat.
AB  - The 92-kDa type IV collagenase (MMP-9) is a metalloproteinase frequently
      localized in both tumor stroma and in tumor cells, particularly at the tumor
      invasion front. To explore the factors regulating transcriptional activation of
      MMP-9 in stromal cells, we used a model system in which fibroblast MMP-9
      expression can be upregulated by cell-cell contact with metastatic transformed
      rat embryo cells. Using transient transfection of reporter gene constructs
      containing 5'-deleted or mutated MMP-9 promoter fragments, as well as
      electrophoretic mobility shift assays, the upstream NFkappaB, SP-1, and Ets sites
      and the downstream AP-1 site and retinoblastoma binding element were shown to be
      necessary for basal transcriptional activity of fibroblast MMP-9. In contrast
      only Ets or SP-1 appeared to be involved in contact-mediated induction of MMP-9.
      Mutation of the upstream AP-1 site increased both basal and contact-stimulated
      promoter activation. Deletion of the alternating purine-pyrimidine repeat in the
      downstream promoter decreased transcriptional activity. Together these findings
      suggest that Ets and SP-1 are the central transcriptional activators of MMP-9
      gene expression in fibroblasts specifically responding to tumor cell contact, and
      that promoter conformation may regulate MMP-9 expression.

PMID- 9514100
TI  - Elevated cyclic AMP suppresses ConA-induced MT1-MMP expression in MDA-MB-231
      human breast cancer cells.
AB  - We have previously reported that induction of MMP-2 activation by Concanavalin A
      (ConA) in MDA-MB-231 human breast cancer cells involves both transcriptional and
      post-transcriptional mechanisms, and that the continuous presence of ConA is
      required for MMP-2 activation (Yu et al. Cancer Res, 55, 3272-7, 1995). In an
      effort to identify signal transduction pathways which may either contribute to or
      modulate this mechanism, we found that three different cAMP-inducing agents,
      cholera toxin (CT), forskolin (FSK), and 3-isobutyl-1-methylxanthine (IBMX)
      partially inhibited ConA-induced MT1-MMP expression and MMP-2 activation in MDA
      MB-231 cells. Combinations of CT or FSK with IBMX exhibited additive effects on
      reduction of MT1-MMP mRNA expression and MMP-2 activation. Agents which increase
      cAMP levels appeared to target transcriptional aspects of ConA induction,
      reducing MT1-MMP mRNA and protein in parallel with the reduced MMP-2 activation.
      In the absence of ConA, down-regulation of constitutive production of MT1-MMP
      mRNA and protein was observed, indicating that cAMP acts independently of ConA.
      These observations may help to elucidate factors regulating MT1-MMP expression,
      which may be pivotal to the elaboration of invasive machinery on the cell
      surface.

PMID- 9514101
TI  - Effect of MRC-5 fibroblast conditioned medium on breast cancer cell motility and
      invasion in vitro.
AB  - We used Transwell chambers to study separately cellular motility and invasion. In
      order to assess the cellular motility, polycarbonate microporous filters were
      coated with extracellular matrix proteins which adsorbed on the filters without
      clogging the pores. To investigate the invasive behavior of tumor cells, filters
      were covered with a layer of Matrigel which clogged the pores. The motility and
      the invasion of breast cancer cell lines (MDA-MB-231, MCF-7/6 and MCF-7/AZ cells)
      were assessed quantitatively in different culture media: defined (serum-free),
      serum-containing and normal human fibroblast MRC-5 conditioned media. In serum
      containing medium, tumor cells migrated and invaded through the coated and
      covered filters. Their motility and invasion potentials were considerably lower
      in defined medium, whereas medium conditioned by MRC-5 fibroblasts stimulated
      both motility and invasion but not growth. The MRC-5 conditioned medium induced
      also the spreading of clusters of MCF-7/6 cells grown on Matrigel-coated plates.

PMID- 9514102
TI  - Molecular biology of varicella-zoster virus. A review prepared for the UK
      Advisory Group on Chickenpox.
AB  - Varicella-zoster virus (human herpesvirus 3; VZV) is one of eight herpes viruses
      that routinely infect humans. It is classified as a member of the genus
      Varicellovirus, subfamily Alphaherpesvirinae, family Herpesviridae. Of the other
      human herpes viruses it is most closely related to the herpes simplex viruses
      (also members of the Alphalerpesvirinae). Like all herpes viruses, the virus has
      a large double-stranded DNA genome within an icosahedral nucleocapsid. This is
      surrounded by a proteinaceous tegument and a trilaminar membrane derived from
      host-cell membranes into which the viral glycoproteins are inserted. The
      structure of the virion is summarized in Fig. 1.

PMID- 9514103
TI  - The immunology of chickenpox. A review prepared for the UK Advisory Group on
      Chickenpox on behalf of the British Society for the Study of Infection.

PMID- 9514104
TI  - Review of 26 years' hospital admissions for chickenpox in North London.
AB  - The epidemiology of chickenpox admissions to an Infectious Diseases Unit was
      studied over 26 years. Risk factors, markers of disease severity, and
      complications were analysed in patients admitted during the last 5 years. Some
      613 patients were admitted with chickenpox over three 5-year periods between 1968
      and 1993. There was a 2.23-fold increase in the number of adults admitted from
      home between the first and last period. Patients of European origin showed a
      three-fold increase. The mean age of adults rose from 26.2 to 34.3 years. Some
      23% of adults had varicella pneumonitis. Smokers were six times more susceptible
      to pneumonitis than were non-smokers. Adult asthmatics were not at increased
      risk, whereas 42% of asthmatic children had chest complications. Seventeen of the
      18 immunocompromised patients had a relatively uncomplicated course. Of the
      children, 32% had secondary skin infections, with no excess complications among
      those with eczema. Thrombocytopenia and elevated aspartate transaminases were
      four times and twice, more frequent in adults than children, respectively. These
      features occurred mostly in males. The male-to-female admission ratio was 2:1 in
      adults, and 1.2:1 in children. Males in both age groups showed a trend to more
      severe disease and more primary complications than did females. Our data showed
      an increase in adult chickenpox admissions. We have identified asthma as a risk
      factor for pulmonary complications in children, but not adults, and male gender
      as an independent risk factor for severe chickenpox.

PMID- 9514105
TI  - Fetal varicella syndrome--a reappraisal of the literature. A review prepared for
      the UK Advisory Group on Chickenpox on behalf of the British Society for the
      Study of Infection.

PMID- 9514106
TI  - Antiviral prophylaxis and treatment in chickenpox. A review prepared for the UK
      Advisory Group on Chickenpox on behalf of the British Society for the Study of
      Infection.
AB  - Prophylactic intervention with varicella-zoster immunoglobulin early in the
      incubation period can prevent or attenuate the disease manifestations of
      varicella in susceptible contacts at high risk from this infection. Detailed
      guidelines are issued in the UK Department of Health publication on Immunization
      against Infectious Disease. Sensitive immunoassays are available for
      investigation of antibody status and subclinical seroconversion. Live attenuated
      varicella vaccine, which has been used successfully post-exposure as well as
      electively elsewhere, is at present not generally available in the UK. Effective
      protocols for prophylaxis against varicella with the antiviral agent aciclovir
      are not yet established. The nucleoside analogue aciclovir (syn: acyclovir,
      Zovirax) is effective in inhibiting replication of VZV when given at a dosage
      higher than that required for treatment of HSV, and is currently the only
      available and approved treatment for varicella in the U.K. Intravenous aciclovir
      therapy for 5-10 days is effective for varicella in neonates and the
      immunocompromised, and for varicella pneumonia or other complications in adults
      and children, if begun early. Oral aciclovir is only effective if begun with 24 h
      of onset of rash. With that proviso. it is recommended for treatment of varicella
      in otherwise healthy adults and adolescents, but not for routine use in children
      under 13 years of age unless they are sibling contacts or have other medical
      conditions. Aciclovir has a high therapeutic index and good safety profile, but
      caution is advised with use in pregnancy.

PMID- 9514107
TI  - Chickenpox in childhood. A review prepared for the UK Advisory Group on
      Chickenpox on behalf of the British Society for the Study of Infection.
AB  - Chickenpox in childhood is a milder condition than in older patients, but serious
      and even fatal complications may occur. These occur especially in
      immunosuppressed individuals, but can also be seen in normal children. The
      commonest of these is secondary bacterial infection with staphylococci or
      streptococci. Reye's syndrome is now rare in chickenpox, since aspirin no longer
      used in treatment. Aciclovir and VZIG (varicella zoster immune globulin) have a
      role in the management of chickenpox in the immunosuppressed or immunodeficient
      child, and aciclovir may be valuable in managing some normal children. Chickenpox
      should not always be considered a trivial illness.

PMID- 9514108
TI  - Management of chickenpox in the adult. A review prepared for the UK Advisory
      Group on Chickenpox on behalf of the British Society for the Study of Infection.

PMID- 9514109
TI  - Varicella infections in pregnancy and the newborn. A review prepared for the UK
      Advisory Group on Chickenpox on behalf of the British Society for the Study of
      Infection.

PMID- 9514110
TI  - Occupational and infection control aspects of varicella. A review prepared for
      the UK Advisory Group on Chickenpox on behalf of the British Society for the
      Study of Infection.

PMID- 9514111
TI  - Summary of questions and answers on chickenpox for primary healthcare personnel.
      Prepared by the UK Advisory Group on Chickenpox.

PMID- 9514112
TI  - Protein distance constraints predicted by neural networks and probability density
      functions.
AB  - We predict interatomic Calpha distances by two independent data driven methods.
      The first method uses statistically derived probability distributions of the
      pairwise distance between two amino acids, whilst the latter method consists of a
      neural network prediction approach equipped with windows taking the context of
      the two residues into account. These two methods are used to predict whether
      distances in independent test sets were above or below given thresholds. We
      investigate which distance thresholds produce the most information-rich
      constraints and, in turn, the optimal performance of the two methods. The
      predictions are based on a data set derived using a new threshold which defines
      when sequence similarity implies structural similarity. We show that distances in
      proteins are predicted more accurately by neural networks than by probability
      density functions. We show that the accuracy of the predictions can be further
      increased by using sequence profiles. A threading method based on the predicted
      distances is presented. A homepage with software, predictions and data related to
      this paper is available at http://www.cbs.dtu.dk/services/CPHmodels/.

PMID- 9514113
TI  - Molecular dynamics simulations of the N-linked oligosaccharide of the lectin from
      Erythrina corallodendron.
AB  - Molecular dynamics simulations have been used to model the flexibility of the
      seven-sugar oligosaccharide of the lectin from Erythrina corallodendron in three
      separate simulations: one of the isolated oligosaccharide in vacuo, one of the
      oligosaccharide in solution and one of the oligosaccharide linked to the protein
      in solution. Adiabatic conformational energy maps were prepared for each of the
      disaccharide linkages as a means of interpreting the observed dynamics and
      conformational averages in terms of intramolecular energy. The inclusion of
      aqueous solvent molecules appears to be necessary to reproduce the experimental
      conformational behavior, which also cannot be predicted well from conformational
      energy maps for the disaccharide linkages alone. The crystallographically
      determined conformation does not appear to be induced by the crystal
      dimerization, but is rather stable in solution. The build-up of fluctuations
      along the successive linkages of the oligosaccharide is significant and would be
      sufficient to prevent branch residues from being located in most crystal
      structure determinations. Good general agreement between the calculated solution
      structure and the average structure determined by NMR was found for most of the
      oligosaccharide linkages.

PMID- 9514114
TI  - Improving the thermostability of Bacillus stearothermophilus neutral protease by
      introducing proline into the active site helix.
AB  - A proline residue was introduced into the N-terminus (Ile140 and Asp141), the
      middle (Leu147) and the C-terminus (Asp153) of the active site helix of Bacillus
      stearothermophilus neutral protease for comparing the effects on the
      thermostability. Introduction of a proline residue into the N-terminus at sites
      140 and 141 increased the half-survival temperature (HST) by 7.5 and 2.8 degrees
      C, respectively, from 68.3 degrees C of the wild-type enzyme. A proline residue
      at Leu147 decreased the HST by 10.2 degrees C, while no change was observed by
      introducing a proline residue in the C-terminus. These results were coincidental
      with the CD data which indicated increases in Tm values of 4.4 and 2.3 degrees C
      for I140P and D141P, respectively. Susceptibility to alpha-chymotrypsin
      hydrolysis markedly decreased in mutants I140P and D141P, while increasing in
      L147P. Molecular modeling suggested that glycine residues on the N-terminus side
      of proline residues in I140P and D141P relaxed the possible strain caused by
      proline introduction. The thermostability can, therefore, be explained based on
      changes in the molecular rigidity.

PMID- 9514115
TI  - Subtilisin from psychrophilic antarctic bacteria: characterization and site
      directed mutagenesis of residues possibly involved in the adaptation to cold.
AB  - A subtilisin excreted by the Antarctic Bacillus TA39 has been purified to
      homogeneity and characterised. Two independent genes subt1 and subt2 are present
      but only subt1 is expressed significantly in the culture medium. The enzyme
      displays the usual characteristics of cold enzymes i.e. a high catalytic
      efficiency at low and moderate temperatures and an increased thermosensitivity
      originating from a 3D structure probably more flexible than its mesophilic
      counterpart. This is corroborated by the analysis of the computerized structure
      which shows a significant decrease in the number and strength of intramolecular
      weak bonds such as salt bridges and aromatic interactions. The affinity for
      calcium is also almost three orders of magnitude lower than that of mesophilic
      subtilisin and the interactions with the solvent are significantly higher thanks
      to a large increase in the number of Asp residues in the loops connecting
      secondary structures. The relation between flexibility and activity was
      investigated by site-directed mutagenesis tending mainly to increase the rigidity
      of the molecular edifice through the incorporation of additional salt bridge,
      disulfide bridge, aromatic interaction and by increasing the affinity of the
      enzyme for calcium. An important stabilization of the molecular structure was
      achieved through a modification of a calcium ligand T85D. The thermostability of
      the mutated product expressed in a mesophilic Bacillus reaches that of mesophilic
      subtilisin. Most important is the fact that this mutation further enhances the
      specific activity by a factor close to 2 when compared to the wild type enzyme so
      that the overall activity of the mutated cold enzyme is about 20 times higher
      than that of mesophilic subtilisin, illustrating the fact that thermostability is
      not systematically inversely related to specific activity. This opens new
      perspectives in the use of cold enzymes in biotechnology.

PMID- 9514116
TI  - Investigations on the thermostability and function of truncated Thermus aquaticus
      DNA polymerase fragments.
AB  - The thermostable DNA polymerase from Thermus aquaticus (Taq polymerase) has been
      truncated to molecular regions essential for polymerase activity. Two truncated
      forms of the full-length 832 amino acid Taq polymerase have been constructed
      according to sequence alignments and the known domain structure of the homologous
      Escherichia coli DNA polymerase I (E.coli pol I): variant delta288 (lacking the N
      terminal 288 amino acid portion) and variant delta413 (lacking the N-terminal 413
      amino acid portion). Both protein fragments were stable and showed polymerase
      activity, albeit specific activity and thermostability of the variant delta413
      were significantly decreased compared with the full length Taq polymerase. In
      order to increase the thermostability of the variant delta413, a three
      dimensional model of the polymerase domain of Taq polymerase was built by
      homology with a model of the Klenow fragment of the E.coli pol I based on the
      available Calpha coordinates. Consequently two variants were designed and
      constructed using site-directed mutagenesis. The strategies used were deletion of
      10 flexible amino acids and replacement of two hydrophobic amino acids on the
      surface by more hydrophilic ones. Compared with the initial protein fragment,
      both variant enzymes showed an increase in polymerase activity and
      thermostability. After the completion of this work, X-ray coordinates of the Taq
      polymerase became available from the protein structure data bank. A comparison
      between the homology model and the experimental three-dimensional structure
      proved the quality of the model.

PMID- 9514117
TI  - Synthesis and characterization of supramolecular protein aggregates: self
      assembled, molecularly-ordered, tubes from electrostatic complementation of
      glutamine synthetase dodecamers.
AB  - Dodecameric Escherichia coli glutamine synthetase (GS) is formed from identical
      subunits arranged in face-to-face hexameric rings. In the presence of Zn2+ and
      other transition metal ions the individual dodecamers 'stack' to form protein
      tubes. Previous results have suggested that six binuclear intermolecular metal
      binding sites are generated at each dodecamer-dodecamer interface by
      juxtaposition of the N-terminal helices of each subunit adjacent to an analogous
      helix from a docked dodecamer. In principle, replacement of one of the metal
      binding sites within each pair of helices with charged amino acids could generate
      electrostatic interactions that would provide the basis for heterospecific
      protein-protein interactions. In turn, this would allow for ordered assembly of
      protein tubes with alternating, chemically distinguishable, components. This
      hypothesis was tested by replacement of one of the metalligating histidines
      (His12) with aspartic acid, arginine or cysteine. The H12C mutant was further
      elaborated by selective thiol modification, with either of the charged reagents 2
      iodo-acetic acid or 2-chloro-acetamidine, which yield glutamate (H12C-IA) or
      arginine (H12C-CA) mimics at position 12. Light scattering and electron
      microscopy were used to monitor the 'stacking ability' of these variants in the
      presence of Zn2+. No, or few, GS 'tubes' were observed in solutions containing
      only H12D, H12R, H12C-CA or H12C-IA, in the presence or absence of Zn2+. In
      contrast, in mixtures containing H12C-CA and either H12D or H12C-IA, the
      complementary GS variants stack in the presence of 100 microM Zn2+, with apparent
      second order rate constants that are comparable to the wild type dodecamers.
      Fluorescence energy transfer experiments with fluorescein-labeled H12C-IA (donor)
      and rhodamine-labeled H12C-CA (acceptor) were performed and compared with the
      energy transfer efficiency with mixtures containing variable ratios of acceptor
      labeled and donor-labeled wild type GS; the wild type mixtures provide a
      benchmark for the extent of energy transfer expected in random linear
      arrangements of donor and acceptor. The efficiency of metal-dependent energy
      transfer in mixtures containing the acceptor-labeled H12C-CA and the donor
      labeled H12C-IA was 3.2-fold greater than expected for a random distribution of
      charged variants. Together, the results indicate that the charged variants
      provide a mechanism for heterospecific interaction between chemically
      distinguishable dodecamers that align in an ordered one-dimensional array.

PMID- 9514118
TI  - Engineering and characterization of a murine MHC class II-immunoglobulin chimera
      expressing an immunodominant CD4 T viral epitope.
AB  - T cells recognize peptides derived from the processing of proteins by antigen
      presenting cells (APCs) in association with the major histocompatibility complex
      (MHC) molecules. We have engineered a murine MHC class II antigen presenting
      molecule consisting of the extracellular domains of I-E(d)alpha and I-E(d)beta
      chains to which the CD4 T cell immunodominant epitope HA110-120 of the
      hemagglutinin (HA) of the A/PR/8/34 influenza virus was covalently linked at the
      N-terminus of the I-E(d)beta chain. The HA110-120-I-E(d)alphabeta complex was
      dimerized by the Fc portion of an IgG2a linked at the C-terminus of the I
      E(d)beta chain. SF9 insect cells infected with baculovirus carrying both I
      E(d)alpha and HA110-120-I-E(d)beta-Fcgamma2a genes, secreted a disulfide
      stabilized dimer of the HA110-120-I-E(d)alphabeta-Fcgamma2a molecule, designated
      as DEF. The chimeric molecule preserved the structural integrity of both MHC
      peptide complex and Fc portion of IgG2a, and was able to: (i) bind specifically
      to the cognate T cell receptors (TCRs) and to the immunoglobulin FcgammaRII
      receptor (FcR), (ii) induce complement-mediated cell cytotoxicity, and (iii)
      trigger early production of IL-2 in cognate T cells. Chimeric antigen presenting
      molecules with these characteristics may represent a novel platform for the
      development of immunomodulatory agents of therapeutic use.

PMID- 9514119
TI  - Isolation of anti-T cell receptor scFv mutants by yeast surface display.
AB  - Yeast surface display and sorting by flow cytometry have been used to isolate
      mutants of an scFv that is specific for the Vbeta8 region of the T cell receptor.
      Selection was based on equilibrium binding by two fluorescently labeled probes, a
      soluble Vbeta8 domain and an antibody to the c-myc epitope tag present at the
      carboxy-terminus of the scFv. The mutants that were selected in this screen
      included a scFv with threefold increased affinity for the Vbeta8 and scFv clones
      that were bound with reduced affinities by the anti-c-myc antibody. The latter
      finding indicates that the yeast display system may be used to map conformational
      epitopes, which cannot be revealed by standard peptide screens. Equilibrium
      antigen binding constants were estimated within the surface display format,
      allowing screening of isolated mutants without necessitating subcloning and
      soluble expression. Only a relatively small library of yeast cells (3 x 10[5])
      displaying randomly mutagenized scFv was screened to identify these mutants,
      indicating that this system will provide a powerful tool for engineering the
      binding properties of eucaryotic secreted and cell surface proteins.

PMID- 9514120
TI  - Novel selection method for engineered antibodies using the mechanism of Fv
      fragment stabilization in the presence of antigen.
AB  - Although the heavy and light chain domains of some antibody variable region
      fragments (Fvs) readily dissociate under physiological conditions, the Fvs are
      stable in the presence of antigen. This 'antigen-driven Fv stabilization
      mechanism' was applied to the selection of clones with specificity toward target
      antigens. The results can be summarized as follows. (i) Some of the residues in
      the heavy chain complementarity determining region 2 (HCDR2) of anti-hen egg
      white lysozyme (HEL) monoclonal antibody HyHEL10 heavy chain variable region (VH)
      were randomized. (ii) The randomized VH fragments of HyHEL10 were displayed on a
      filamentous bacteriophage and mixed with the target antigen, before being applied
      to a light chain variable region (VL) which was immobilized on microtiter plates
      and subjected to selection by panning. (iii) After four rounds of panning, four
      clones that showed significant binding to human lysozyme (hL), which HyHEL10
      recognized poorly, were selected from the HCDR2 library. (iv) The soluble Fv
      fragments selected were expressed in Escherichia coli, purified, and subjected to
      an inhibition assay of lysozyme enzymatic activities and an isothermal titration
      calorimetry. These Fv fragments had increased affinity toward hL, and
      thermodynamic analysis suggested that the reduced entropy loss due to binding by
      the replacement of residues in HCDR2 resulted in the higher hL binding activity.

PMID- 9514121
TI  - Functional expression of adhesive peptides as fusions to Escherichia coli
      flagellin.
AB  - An expression system for studying epitopes of adhesion proteins based on fusion
      of gene fragments into fliC(H7) of Escherichia coli is described. We constructed
      the system by an in-frame insertion of DNA fragments encoding one, two or three
      of the fibronectin-binding D repeats present in the fibronectin-binding protein A
      (FnBPA) of Staphylococcus aureus, into the fliC(H7) gene region encoding the
      variable domain of the H7 flagellin. The constructs were expressed by in trans
      complementation in the E. coli strain JT1 which harbours knock-out mutations for
      the expression of FliC as well as of the mannoside-binding fimbrial adhesin. The
      resulting chimeric flagella, which contained 39, 77 or 115 heterologous amino
      acid residues, efficiently bound soluble and immobilized human plasma and
      cellular fibronectin, and the binding was most efficient with the flagella
      containing the three D repeats of FnBPA. The chimeric flagella bound to frozen
      sections of human kidney and to cultured human cells. Antibodies raised against
      the chimeric flagella bound to Protein A-deficient S. aureus cells and inhibited
      the binding of staphylococci to immobilized fibronectin. We also expressed
      peptides, ranging in size between 48 and 302 amino acids, of the collagen-binding
      YadA adhesin of Yersinia enterocolitica. A fragment of 302 amino acids
      representing the middle region of YadA was needed for collagen binding. Chimeric
      flagellar filaments expressing hundreds of intimately associated adhesive
      epitopes offer versatile tools to analyze adhesin-receptor interactions and
      functional epitopes of adhesion proteins.

PMID- 9514122
TI  - Expression, purification and characterization of the homeodomain of rat ISL-1
      protein.
AB  - Isl-1 is a member of a family of Homeodomains containing proteins that possess an
      N-terminal pair of zinc binding LIM domains. The Isl-1 gene in rat codes for a
      protein that binds to the insulin gene enhancer and is also involved in
      regulation of amylin and proglucagon genes. A DNA sequence coding for 66 amino
      acid residues containing the C-terminal homeodomain fragment of Isl-1 was
      expressed as a soluble protein in Escherichia coli. Here, we describe a procedure
      which allows the rapid native purification of recombinant homeodomain protein
      fused to an N-terminal tag of six histidines. The purified homeodomain showed DNA
      binding activity to its cognate DNA sequence. An enhanced binding activity is
      observed in the presence of a reducing agent in electrophoretic mobility shift
      assays. The DNA binding was further characterized by circular dichroism
      spectroscopy. Addition of DNA to the homeodomain did not change the overall
      secondary structure content, but the thermal and chemical denaturing profiles
      were altered. A stabilization of the secondary structure was observed upon DNA
      binding. The free energy of unfolding at 23 degrees C was 7 kJ mol(-1) in absence
      of DNA and 29 kJ mol(-1) in the presence of DNA.

PMID- 9514123
TI  - Improvement of the refolding yield and solubility of hen egg-white lysozyme by
      altering the Met residue attached to its N-terminus to Ser.
AB  - When hen egg-white lysozyme was produced in Escherichia coli, it possessed an
      extra methionine residue at the N-terminus (Met(-1)-lysozyme). The Met(-1)
      lysozyme showed a decreased refolding yield and solubility compared with the
      native hen egg-white lysozyme, as the methionine is a hydrophobic amino acid. A
      Met(-2)Pro(-1) or Met(-2)Ser(-1) sequence was introduced at the N-terminus of hen
      egg-white lysozyme. The methionine residue in these hen egg-white lysozymes was
      completely removed by methionine aminopeptidase, as expected, since the
      penultimate residue was proline or serine. From the analyses of solubility,
      stability and refolding yield, it was found that an extra Ser residue attached to
      the N-terminus of hen egg-white lysozyme (Ser(-1)-lysozyme) showed closer
      characteristics to the native hen egg-white lysozyme than did Met(-1) or an extra
      Pro residue attached to the N-terminus of hen egg-white lysozyme (Pro(-1)
      lysozyme). Moreover, the tertiary conformation of Ser(-1)-lysozyme examined by
      NMR spectroscopy and its activity were almost identical with those of native hen
      egg-white lysozyme.

PMID- 9514124
TI  - High-level expression of bovine beta-lactoglobulin in Pichia pastoris and
      characterization of its physical properties.
AB  - Bovine beta-lactoglobulin (BLG) variant A has been expressed in the methylotropic
      yeast Pichia pastoris by fusion of the cDNA to the sequence coding for the alpha
      mating factor prepro-leader peptide from Saccharomyces cerevisiae. P. pastoris
      Mut+ transformants were obtained by single cross-over integration of the BLG
      containing vector into the AOX1 locus. In a fed-batch fermenter, a cell density
      of approximately 300 mg/ml was achieved by controlled glycerol feeding for a
      total of 24 h. After 72 h of methanol induction, the secreted BLG reached levels
      of > 1 g/l. The secreted protein could be purified to homogeneity by ion-exchange
      chromatography. Amino-terminal sequencing of the secreted BLG revealed that the
      Glu-Ala spacer repeats inserted between the mature protein and the alpha-factor
      prepro-leader were still present. The purified protein was characterized by a
      number of methods, including CD spectroscopy, guanidine-HCl unfolding,
      crystallization and two-dimensional 1H-NMR spectroscopy. By all of these
      measures, the physical characteristics of recombinant BLG were indistinguishable
      from those of the native purified bovine BLG, making it useful as a model for
      protein folding and other biophysical studies.

PMID- 9514125
TI  - Association properties of betaB2- and betaA3-crystallin: ability to form dimers.
AB  - The beta-crystallins are a major constituent of the mammalian lens, where they
      associate into dimers, tetramers and higher order aggregates. Appropriate
      association of lens crystallins is important for lens transparency. To examine
      the associative properties of betaB2-crystallin, we have expressed mouse betaB2
      crystallin using a baculovirus system. Recombinant mouse betaB2-crystallin has an
      estimated monomer molecular weight of 24 kDa by SDS-PAGE, appropriate
      immunoreactivity and appropriate secondary structure as assessed by circular
      dichroism analysis. The recombinant betaB2-crystallin associates into a homodimer
      with a weight average molecular mass of 39 kDa. The betaB2-crystallin homodimer
      has an estimated Kd of 5 x 10(-6) M, slightly greater than that of betaA3
      crystallin, 0.8 x 10(-6) M. When recombinant betaB2-crystallin is combined with
      recombinant betaA3-crystallin, a heterodimer is formed within 10 min of
      incubation at room temperature. When equilibrium is reached in 4-6 h,
      approximately half of each crystallin associates into heterodimers. Subunit
      exchange between betaB2-crystallin and betaA3-crystallin occurs readily in the
      absence of any denaturing agents. Thus, rbetaA3-rbetaB2 heterodimer formation can
      occur under conditions similar to those found in the eye lens.

PMID- 9514126
TI  - Behcet's Disease.
AB  - OBJECTIVES: To review the new data on the epidemiology, etiopathogenesis,
      clinicolaboratory spectrum, prognosis, and treatments of Behcet's disease (BD).
      METHODS: The information concerning the etiopathogenesis of the disease is
      divided into infection, immune, and genetic factors. The clinical features of the
      disease are discussed according to the organ or system involved. Treatment is
      described as general, local, and systemic. RESULTS: BD is a multisystem
      vasculitis with recurrent symptoms. It affects mainly people living around the
      Mediterranean basin and in Japan. The mean age at onset is the third decade.
      Children are rarely affected, and few neonatal cases have been reported. In large
      series of patients, men predominate over women. Infectious agents, immune
      mechanisms, and genetic factors are implicated in the etiopathogenesis of the
      disease, which remains to be elucidated. The pathology of the lesions consists of
      widespread vasculitis. Eyes, skin, joints, the oral cavity, blood vessels, and
      central nervous system are usually involved, although less frequently the heart,
      lung, kidney, genital system, and gastrointestinal tract may be affected. The
      prognosis of the disease has been improved because of early diagnosis and
      suitable treatment. Local remedies and systemic administration of colchicine,
      corticosteroids, immunosuppressives, and other agents have been applied.
      CONCLUSION: BD is a widespread vasculitis affecting young people and involving
      concurrently or consecutively nearly all organs and systems. Treatment results in
      better prognosis even when vital organs are involved.

PMID- 9514127
TI  - Autoimmune manifestations of the Wiskott-Aldrich syndrome.
AB  - OBJECTIVE: To describe and review the autoimmune features and typical
      manifestations of Wiskott-Aldrich syndrome (WAS). DESIGN: Case series and review
      of the literature. SETTING: Tertiary care medical center and pediatric referral
      center. PATIENTS: The presentation, diagnosis, and management of two cases are
      reported. In addition to the typical features of WAS, the first patient had
      hemolytic anemia, arthritis, leukocytoclastic vasculitis, and colitis. The second
      patient had colitis and arthralgias. Detailed review of features and therapeutic
      options in WAS as exemplified by these two patients are presented. Both patients
      had bone marrow transplantation, the only definitive treatment for WAS.
      CONCLUSIONS: WAS has variable clinical and autoimmune manifestations. Diagnosis
      must be suspected in a boy with small, decreased number of platelets and
      autoimmune problems or infections. Bone marrow transplantation is the only
      successful mode of treatment for all aspects of WAS.

PMID- 9514128
TI  - Role of the new azoles in the treatment of fungal osteoarticular infections.
AB  - OBJECTIVES: To analyze the usefulness of the new azoles for the treatment of
      fungal osteoarticular infections, and to report three cases of fungal knee
      arthritis treated with fluconazole in our unit. METHODS: The medical literature
      was reviewed for all cases of osteoarticular infection caused by fungi and
      treated with fluconazole or itraconazole registered in the MedLine Silver Platter
      database from 1972 to 1997. RESULTS: The total number of patients included in
      this review was 56; 19 were treated with fluconazole and 37 with itraconazole.
      The most frequent causative agents implicated were fungi of the genuses Candida
      and Aspergillus. There were eight therapeutic failures, and there were no
      statistically different findings among the patients in terms of their health
      status. Adverse effects were unusual. CONCLUSIONS: Controlled studies are
      necessary to establish the true role of the new azole drugs in the treatment of
      fungal osteoarticular infections, but they seem to be a promising therapeutic
      option.

PMID- 9514129
TI  - Evaluation and treatment of postmenopausal osteoporosis.
AB  - OBJECTIVES: To review the recent literature and develop a logical strategy with
      which to approach the diagnosis and treatment of osteoporosis, based on clinical
      evidence and accepted practices. METHODS: Published reports from 1983 through
      1997 obtained by MEDLINE search were reviewed and analyzed by both authors.
      RESULTS: Osteoporosis is a widespread medical condition readily identifiable by
      current diagnostic modalities, including quantitative computed tomography, single
      and dual x-ray absorbtiometry, radio-absorbtiometry, and ultrasound. Properly
      implemented prevention and treatment strategies, such as calcium and vitamin D
      supplementation, exercises, hormone replacement therapy, alendronate, and
      calcitonin, may reduce the future fracture risk in many individuals. An algorithm
      is provided based on currently available clinical evidence for the evaluation and
      treatment of osteoporosis. CONCLUSIONS: Expanded use of currently available and
      emerging diagnostic and therapeutic modalities should lead to decreased fracture
      rates and a resultant increase in quality of life for patients with osteoporosis.

PMID- 9514130
TI  - Coagulation and fibrinolytic parameters in normal pregnancy and in pregnancy
      complicated by intrauterine growth retardation.
AB  - The objective of this article is to evaluate the plasma levels of coagulation and
      fibrinolysis parameters in the third trimester of gestation and 72 hr
      postdelivery. Antithrombin III (ATIII), thrombin-antithrombin III complexes
      (TAT), heparin cofactor II (HCII), protein C (PC), protein S (PS), tissue
      plasminogen activator (t-PA), D-dimer, and plasminogen activator inhibitors (PAI
      1 and PAI-2) levels in uncomplicated pregnancies and in pregnancies complicated
      by intrauterine growth retardation (IUGR) have been determined. Normal pregnant
      women (n = 63) and women whose was complicated by IUGR (n = 10) formed the study
      population. Coagulation and fibrinolysis parameters were estimated using
      commercial tests. There were no differences in ATIII, HCII, and PS levels between
      normal and IUGR pregnancies. TAT, t-PA, and D-dimer levels were higher in IUGR
      pregnancy than in the uncomplicated pregnancy group. PAI-1 and PAI-2 were found
      depressed in IUGR pregnancy when compared with normal pregnancy. Changes in
      coagulation and fibrinolytic systems occur in plasma of women with pregnancies
      complicated by IUGR. The results suggest an activation of the coagulation system
      in pregnancies complicated by IUGR. Reduced PAI-2 and high TAT levels correlate
      with birth weight. In IUGR pregnancies a hypercoagulative state with
      hyperfibrinolytic compensatory mechanisms is suggested.

PMID- 9514132
TI  - Umbilical venous catheter retrieval under fluoroscopy in a very low-birth-weight
      infant.

PMID- 9514131
TI  - Association of tocolytic therapy with antenatal steroid administration and infant
      outcomes. Newborn Lung Project.
AB  - The use of tocolytic agents to halt premature labor is controversial. We examine
      a database on very low-birth-weight infants born following the onset of premature
      labor (n = 540) for association between tocolytic and antenatal steroid therapy,
      and to assess neonatal and childhood outcomes following combined therapy. Data
      are from a multicenter regionally based study of all infants below 1501 g at
      seven neonatal intensive care units (NICUs) in Wisconsin and Iowa, born August 1,
      1988 through June 30, 1991. Infant outcomes analyzed are death in the first 30
      days, respiratory distress syndrome (RDS), and intraventricular hemorrhage (IVH).
      Fewer deliveries occurred within 12 hours of labor onset with tocolytics (61 vs.
      75% without). A strong association between tocolytic therapy and antenatal
      steroid administration was found [adjusted odds ratio OR = 5.7, 95% confidence
      interval CI: (3.3, 10.0)]. Tocolytics were associated with lower mortality in the
      first 30 days [OR = 0.29, CI: (0.15, 0.56)]. Joint administration of tocolytics
      and antenatal steroids versus neither was associated with lower incidence of the
      combined outcome of respiratory distress syndrome (RDS) or death [OR = .30, CI:
      (0.15, 0.60)] and grade III-IV IVH or death [OR = 0.35, CI: (0.14, 0.98)].
      Tocolytic therapy alone was not associated with IVH grade III-IV [OR = 1.0, CI:
      (0.57, 1.9)] among survivors.

PMID- 9514133
TI  - Outcome of 496 term singleton breech deliveries in a tertiary center.
AB  - The study was conducted to compare the neonatal and maternal outcome of breech
      infants delivered vaginally at term with those delivered by cesarean section. All
      singleton term breech deliveries between January 1, 1992 and December 31, 1994
      were reviewed (n = 496). Criteria for eligibility for vaginal trial of labor
      included: frank or complete breech presentation, estimated fetal weight of 2000
      3800 g, no hyperextension of the fetal head and no history of uterine scar (group
      A, n = 283). Patients who did not fulfill these criteria, or had an abnormal
      pelvimetry, were delivered by cesarean section without a trial of labor (group B,
      n = 213). In group A, 226 patients (80%) delivered vaginally, and 57 (20%)
      patients underwent a cesarean section; 70% of the nulliparae and 89% of the
      multiparae delivered vaginally. No differences were observed between the groups
      in gestational week, number of nulliparae, pregnancy complications, and rates of
      epidural analgesia. However, maternal age and birth weight were significantly
      higher in group B. No maternal or perinatal mortality occurred. The incidences of
      5-min Apgar score <7, birth trauma, neonatal complications, and neonatal
      intensive care unit admissions were similar between the groups and in the
      nulliparae and multiparae of each group. Maternal morbidity was significantly
      lower in patients who delivered vaginally. We conclude that a trial of labor in
      breech presentation based on appropriate selective criteria, and an active policy
      of labor management performed by experienced physicians, will facilitate safe
      delivery in most nulliparae and multiparae.

PMID- 9514134
TI  - Alveolar capillary dysplasia, with and without misalignment of pulmonary veins:
      an association of congenital anomalies.
AB  - Two new cases of alveolar capillary dysplasia (ACD), one without misalignment of
      the pulmonary vessels (MLV), are reported. They are unique for their association
      with complex cardiac malformations and asplenia. By reporting these cases we want
      to stress that ACD is associated with multiple malformations, and that the
      absence of MLV does not rule out the diagnosis of ACD.

PMID- 9514136
TI  - Fetal oxygen saturation during maternal bearing down efforts in the second stage
      of labor.
AB  - Fetal oxygen saturation (FSpO2) was monitored with the Nellcor Puritan Bennett
      N400/FS14 system during 16 labors to establish whether FSpO2 was influenced by
      maternal bearing down efforts in the second stage of labor. Fetal SpO2 is
      reported for 16 fetuses where neonatal outcome was normal. One hour of continuous
      data was recorded: 30 min prior to the onset of maternal bearing down efforts and
      the first 30 min of pushing. The hour was divided into six epochs of 10-min
      duration. Differences between mean FSpO2 for the two 30 min of monitoring and for
      each epoch were sought using repeated measures analysis of variance (ANOVA). The
      mean FSpO2 for the total 30 min prior to the onset of pushing was 49% (95%
      confidence intervals 46.5-50.6%), compared to a mean of 46% (95% confidence
      intervals 43.6-48.7%) during the first 30 min of pushing [F (1, 2.25), p = 0.14].
      There was no significant decline in mean FSpO2 for each epoch. Apgar scores at 5
      min were all > 7 and umbilical arterial pH values were > or = 7.20 (n = 12). We
      concluded that mean FSpO2 recorded prior to the onset of maternal bearing down
      efforts was not significantly different to mean FSpO2 during pushing, with normal
      neonatal outcome.

PMID- 9514135
TI  - Decreased renal and hepatic blood flow with preeclampsia-like histologic changes
      was obtained by stimulation of the celiac ganglion with LPS.
AB  - Decreased renal and hepatic blood flow with preeclampsia-like histologic changes
      was developed by stimulation of the celiac ganglion with lipopolysaccharide (LPS)
      in pregnant rabbits. The renal and hepatic blood flow were measured after
      stimulation of the celiac ganglion with 10 microL (group 1), 100 microL (group
      II) and 300 microL (group III) of LPS (10 mg/mL conc.) and with 100 microL of
      normal saline (group IV). The bifurcation of the abdominal aorta was also
      stimulated with 300 microL of LPS (group V). A control experiment was also done
      in this study (group VI). Histopathological studies of kidney and liver tissue
      were also performed in this protocol. A significant reduction in renal and
      hepatic blood flow was observed in pregnant rabbits with the times and dosage
      dependent on stimulation of the celiac ganglion by LPS. Stimulation of the
      bifurcation of the abdominal aorta with LPS could not produce any changes in
      renal and hepatic blood flow. Preeclampsia-like histologic changes of kidney and
      liver tissue were also observed. These results suggest that exogenous stimulation
      of the celiac ganglion causes decreased renal and hepatic blood flow, resulting
      in preeclampsia-like histologic changes of kidney and liver in pregnant rabbits.

PMID- 9514137
TI  - The effect of ethnicity on the development of small for gestational age infants
      associated with hypertension in pregnancy.
AB  - The objective of this article is to assess in a hypertensive pregnant population
      the role of ethnic background on the development of small for gestational age
      (SGA) infants. A cohort population of 366 pregnant women who developed new
      hypertension in their pregnancy were interviewed and their ethnic groups defined.
      We then compared the outcomes of the pregnancies with regard to the development
      of SGA infants among the various ethnic groups. Preeclamptic women were more
      likely to deliver a SGA infant than gestational hypertensive women. Women of East
      Indian descent delivered the highest incidence of SGA infants when they developed
      preeclampsia (50%) compared to an incidence in the White population of 13.8%.
      Only the ethnocultural group, mean third-trimester blood pressure and third
      trimester hematocrit, significantly correlated with the development of a SGA
      infant. Chinese and East Indian women who develop preeclampsia are at the highest
      risk of having a growth-restricted infant.

PMID- 9514138
TI  - Transvaginal sonography of the forewaters in the assessment of amniotic fluid
      volume in patients with oligohydramnios.
AB  - OBJECTIVE: To determine whether the forewaters should be considered in the
      assessment of amniotic fluid (AF) volume in patients beyond 37 weeks' gestation.
      METHODS: Sixty patients were prospectively studied and designated as having
      oligohydramnios or normal AF volume based upon on the standard four-quadrant AF
      index (AFI) of < or = 5 cm or > 5 cm, respectively. The distance between the
      internal os and the fetal head was measured transvaginally. This measurement was
      first added to the standard AFI and subsequently interchanged with the lowest of
      the two lower abdominal quadrant measurements. Statistical analysis included
      Student's t-test with p < 0.05 considered significant. RESULTS: Thirty patients
      were classified as oligohydramnios and 30 normal AF volume. The two subgroups did
      not differ as to maternal age, parity, gestational age at sonographic
      examination, incidence of meconium-stained amniotic fluid or 5-min Apgar scores <
      7, or birth weight. No significant difference was noted between the mean
      forewaters measurement of patients with oligohydramnios and controls (0.2 +/- 0.1
      and 0.4 +/- 0.1 cm, respectively). In patients with oligohydramnios, there was no
      significant difference between the standard AFI and the AF volume with the
      forewaters in each of the methods assessed (2.7 +/- 0.3, 2.9 +/- 0.3, and 2.7 +/-
      0.3 cm, respectively). CONCLUSION: We conclude that various permutations of the
      AFI, which include sonographic assessment of the forewaters, do not impact on the
      diagnosis of oligohydramnios.

PMID- 9514139
TI  - Evidence for the safety of ascorbic acid administration to the premature infant.
AB  - Ascorbic acid (AA), a plasma antioxidant, is maintained at high levels in
      premature fetal blood and declines rapidly postpartum. The sudden reduction in
      blood AA levels secondary to premature delivery may increase the risk of oxidant
      injury, that is, bronchopulmonary dysplasia and intraventricular hemorrhage.
      There is concern that administration of AA to premature infants, in an effort to
      increase antioxidant capacity, may cause hemolysis. We felt that the benefits of
      early AA administration and prevention of the immediate postnatal drop in blood
      AA levels, might outweigh the risks of erthrocyte damage. Fifty one high-risk
      premature infants were randomized to receive either normal saline or 100 mg/kg of
      AA, daily for the first week of life. Double-blind comparisons were made of
      hemoglobin, hematocrit, erythrocyte morphology, bilirubin, number of blood
      transfusions and days of phototherapy, renal function tests, the incidence of
      infection, bronchopulmonary dysplasia, and intraventricular hemorrhage during the
      first month of life. The administration of AA prevented the immediate postnatal
      drop in AA and was not associated with evidence of increased hemolysis. No
      significant differences in renal function, rate of infection, bronchopulmonary
      dysplasia, or intraventricular hemorrhage were seen between the two groups. This
      study suggests that AA administration to the premature infant is safe and
      supports the designing and performance of larger clinical studies of the
      antioxidant properties of AA.

PMID- 9514140
TI  - Equation for predicting weight gain in very low-birth-weight infants.
AB  - I developed a single equation that simulated previously published growth charts
      for very low-birth-weight infants, using birth weight as the only variable. The
      intent of this study was to validate the equation using infants admitted to our
      neonatal intensive care unit (NICU) and to determine if this equation could be
      used as a research tool to compare weight gain among populations. All 171
      surviving infants with birth weight < or = 1500 g who received care in our NICU
      were studied retrospectively. The individual daily weights were compared with the
      predicted daily weights for each infant using the relative error of the
      prediction. The relative error of the prediction on all days for all infants was
      0.45 +/- 0.13% (mean +/- SEM), and the maximum mean daily relative error of 2.73
      +/- 0.90% occurred on Day 9. Black infants had a more positive relative error
      than white infants (p = 0.0001), due to faster weight gain. Twins gained faster
      than singletons (p = 0.023). Infants with patent ductus arteriosus (PDA) gained
      more slowly than normal infants (p = 0.001) after an initial rapid weight gain.
      Infants with lung disease had initial rapid weight gain similar to infants with
      PDA, but subsequently were similar to infants without lung disease. This equation
      accurately predicts weight gain in our population of very low-birth-weight
      infants. The relative error of the prediction is a useful research tool for
      determining the effect of clinical conditions or interventions on weight gain.

PMID- 9514141
TI  - Urological dysfunctions and upper urinary tract involvement in multiple sclerosis
      patients.
AB  - The goal of the present study was to investigate the involvement of the upper
      urinary tract (UUT) in patients with multiple sclerosis and its relationship with
      other neurological and urological features of the disease. One hundred sixteen
      patients underwent complete neurological and urological assessments, urodynamic
      investigation, and morphofunctional study of the urinary tract by
      ultrasonography, voiding cistourethrography, and/or intravenous excretory
      pyelography. The most remarkable relationships were observed among disease
      duration, pyramidal system score, amplitude of uninhibited detrusor contractions
      and the presence of bladder morphological abnormalities (P = 0.03, 0.0008, and
      0.018, respectively) and the relationship between pyramidal system score or the
      presence of bladder pathology and UUT abnormalities (P = 0.03 and 0.0006,
      respectively). A significant relationship was found between the maximum amplitude
      of uninhibited contractions and UUT involvement (P = 0.002). No other significant
      relationship was observed between UUT involvement and any other urodynamic or
      urological features of the disease (type of progression and progression rate,
      Expanded Disability Status Scale, and other functional system scores). The
      relationship among disease duration, high vesical pressures, and the lack of
      reliable clinical indices of risk to the UUT stress the importance for patients
      with multiple sclerosis to adhere to a strict follow-up program with urodynamic
      assessment and urinary tract imaging and to maintain detrusor relaxation with
      anticholinergic medications.

PMID- 9514142
TI  - Relationships between lower urinary tract symptoms and bladder outlet
      obstruction: results from the ICS-"BPH" study.
AB  - Despite the lack of evidence in the literature for close relationships between
      lower urinary tract symptoms and bladder outlet obstruction, the majority of
      urologists rely on symptomatology when selecting patients for prostatic surgery.
      We investigated the relationships between a wide range of lower urinary tract
      symptoms from the ICSmale questionnaire and the results of urodynamic pressure
      and flow studies. We evaluated 933 patients with lower urinary tract symptoms
      suggestive for bladder outlet obstruction from 12 countries who participated in
      the ICS-"BPH" study with the ICSmale questionnaire and urodynamic pressure and
      flow studies. Spearman rank correlation coefficients were obtained between
      symptoms and measures of bladder outlet obstruction. There was little or no
      correlation between a wide range of symptoms and the results of free uroflowmetry
      and pressure and flow studies. From symptoms alone, it is not possible to
      diagnose bladder outlet obstruction. Pressure and flow studies and symptom
      profiles measure different aspects of the clinical condition that should be
      viewed separately in the evaluation and treatment decision of the patient
      presenting with lower urinary tract symptoms.

PMID- 9514143
TI  - Analysis of outcome after thermotherapy using different classifications of
      bladder outlet obstruction.
AB  - The urodynamic profiles of 97 patients with benign prostatic hyperplasia
      undergoing low-energy transurethral microwave thermotherapy (TUMT) for lower
      urinary tract symptoms were analysed using the Abrams/Griffiths nomogram, the
      urethral resistance algorithm, the linPURR, Schafer nomogram, and the CHESS
      classification. A significant clinical response was seen for the whole group, as
      shown by changes in symptom score, free flow rate, and residual urine. The best
      symptomatic response was identified in patients in whom obstruction was present,
      whatever the classification used. Only the two-dimensional CHESS classification
      was found to predict a group of patients with a better response in both symptoms
      and objective variables. Obviously, a better response from TUMT can only be
      predicted by a classification system that identifies the independent variables of
      footpoint and slope of the PURR. The CHESS classification was the only one of
      those studied that satisfactorily identified these two parameters and could be
      used as a system of case selection for this minimally invasive treatment.

PMID- 9514144
TI  - Supine empty stress test as a predictor of low valsalva leak point pressure.
AB  - Our objective was to determine whether a positive supine empty stress test is
      predictive of a low Valsalva leak point pressure (< or =60 cm of water).
      Evaluation was carried out on 179 patients with a history of genuine stress
      incontinence confirmed with urodynamic testing. All patients had a supine stress
      test performed after voiding. Residual urine determinations were all <100 cc. A
      vesical Valsalva leak point pressure determination (cough and strain) was
      performed during multichannel urodynamics with 150 cc in the bladder. Urethral
      profilometry was performed at maximum capacity. There was a statistically
      significant relationship between a low leak point pressure and a positive supine
      empty stress test (P < 0.000). The supine empty stress test had a sensitivity of
      79% and a specificity of 62.5% for the detection of a low leak point pressure.
      The negative predictive value was high at 90%. For the age group 50 years and
      younger the negative predictive value was 95%. However, there was no significant
      relationship between a positive supine empty stress test and a low maximal
      urethral closure pressure. We conclude that the supine empty stress test is a
      useful screening test for a low leak point pressure but not a low urethral
      closure pressure. Its high negative predictive value is useful in excluding the
      presence of a low leak point pressure and may help the clinician to determine
      which patients with genuine stress incontinence need further assessment of the
      dynamic function of the urethral sphincter.

PMID- 9514145
TI  - Detrusor pressure in ambulatory versus standard urodynamics.
AB  - An ambulatory urodynamic examination was performed on 28 non-neurogenic
      incontinent patients in whom classical cystometry could not confirm objectively
      the history and clinical diagnosis of urinary incontinence. In 12 of 13 stress
      incontinent patients, real leakage could be demonstrated. Of 15 patients with
      mixed incontinence, bladder instability was found in 8 and urethral instability
      in 2. Voiding detrusor pressures in ambulatory measurements were approximately 10
      cm H2O higher than in classical cystometry, although the voided volumes were
      lower. Advantages and pitfalls of ambulatory detrusor pressure monitoring are
      discussed.

PMID- 9514146
TI  - Role of type III collagen in bladder filling.
AB  - The function of the urinary bladder is to store urine at low pressure and expel
      it periodically. To accomplish this, it must have the appropriate structural
      properties to accommodate slow but continuous volume changes. While much is
      presently known about the functional measurements of compliance, relatively
      little is known about the structural basis of compliance. In the present study,
      immunohistochemistry has been used to localize type III collagen fibers in the
      bladder wall at different intravesical volumes. To improve the resolution of
      these fibers, confocal microscopy was utilized to determine the changes in type
      III collagen fiber orientation and correlate them with the degree of mechanical
      distension of the bladder wall at partial and full capacity. We demonstrate that
      there were significant changes in both the orientation and conformation of type
      III collagen fibers during bladder filling. These observations support the view
      that volume accommodation in the bladder is achieved by changes in the
      arrangement of type III collagen. These data suggest that abnormal deposition or
      arrangement of type III collagen fibers can have an impact on normal bladder
      function.

PMID- 9514147
TI  - Lack of effect following repeated in vivo exposure of the rabbit urinary bladder
      to urine from interstitial cystitis patients at low infusion volumes.
AB  - We reported previously that substances in interstitial cystitis urine, when
      infused into the rabbit bladder, induce changes that resemble bladders of
      interstitial cystitis (IC) patients. Here we report our investigation of the
      effect of additional molecular weight subfractions of IC urine and lower infusion
      volume in this rabbit bladder bioassay. Urine was pooled from symptomatic IC
      patients, asymptomatic IC patients (in remission), and normal volunteers. Two
      fractions of 20x concentrated urine were obtained for each of the 3 groups: a 10
      100-kD fraction and a fraction > 100 kD but <0.22 microm. Six rabbits per group
      were infused twice per week with 6 ml of 1 of these 6 urine fractions or saline
      as a control. After 6 weeks, each rabbit was cystoscoped before and after
      hydrodistension, bladder capacity and urea permeability were determined, and the
      bladder was removed for histologic examination. A questionnaire revealed a
      significant difference (P < 0.01) regarding voiding symptom severity between
      symptomatic IC patients and both normal volunteers and IC patients in remission.
      There was no statistically significant difference among groups of rabbits in
      cystoscopic bladder appearance, bladder capacity, urea permeability, or bladder
      histology. If a urine-borne factor is in part responsible for IC symptoms, the
      rabbit bladder must be filled with urine to near capacity to be able to detect a
      difference between IC and normal urine in this rabbit bladder bioassay.

PMID- 9514148
TI  - Standards of efficacy for evaluation of treatment outcomes in urinary
      incontinence: recommendations of the Urodynamic Society.

PMID- 9514149
TI  - Retinoid receptor-induced alteration of the chromatin assembled on a ligand
      responsive promoter in Xenopus oocytes.
AB  - Retinoic acid (RA) stimulates transcription from the retinoic acid receptor beta2
      (RARbeta2) promoter in mammalian embryonal cells. Evidence by in vivo
      deoxyribonuclease I (DNase I) hypersensitivity assay indicates that RA treatment
      of these cells results in an alteration of chromatin structure in and near the
      promoter. To study the role of chromatin in RA-activated transcription, we
      assembled the RARbeta2 promoter into chromatin in Xenopus oocytes. Ectopic
      expression of RAR and retinoid X receptor (RXR) enhanced transcription without
      ligand, irrespective of whether chromatin was assembled in a replication
      dependent or -independent manner, although ligand addition led to a further,
      marked increase in transcription. Moreover, expression of RAR and RXR, without
      ligand addition, induced DNase I-hypersensitive sites in the chromatin-assembled
      promoter. Furthermore, expression of RAR and RXR in oocytes led to local
      disruption of chromatin assembled over the promoter without ligand. Similar
      ligand-independent, but RXR/RAR-dependent nucleosomal disruption was observed in
      an in vitro chromatin reconstitution system using Drosophila embryonic extracts.
      Thus, unliganded receptors expressed in oocytes are capable of accessing to the
      chromatin-assembled promoter and activating transcription without ligand,
      indicating that chromatin assembly per se is not sufficient to reproduce ligand
      dependent chromatin changes and promoter activation seen in mammalian cells. The
      oocyte system may serve as a model to study mechanisms of RA-dependent
      alterations of chromatin structure.

PMID- 9514150
TI  - Identification of critical residues for heterodimerization within the ligand
      binding domain of retinoid X receptor.
AB  - Nuclear receptors regulate transcription by binding to specific DNA response
      elements as homodimers or heterodimers with the retinoid X receptors (RXRs). The
      identity box (I-box), a 40-amino acid region within the ligand-binding domains of
      RXRs and other nuclear receptors, was recently shown to determine identity in the
      heterodimeric interactions. Here, we dissected this region in the yeast two
      hybrid system by analyzing a series of chimeric receptors between human RXRalpha
      and rat hepatocyte nuclear factor 4 (HNF4), a distinct member of the nuclear
      receptor superfamily that prefers homodimerization. We found that the C-terminal
      11-amino acid region of the RXR I-box was sufficient to direct chimeric receptors
      based on the HNF4 ligand-binding domain to heterodimerize with retinoic acid
      receptors or thyroid hormone receptors. Furthermore, we identified the hRXRalpha
      amino acids A416 and R421 of the 11-amino acid subregion as most critical
      determinants of heterodimeric interactions; i.e. mutant HNF4s incorporating only
      the hRXRalpha A416 or R421 heterodimerized with retinoic acid receptor.

PMID- 9514151
TI  - Androgen responsiveness of mouse kidney beta-glucuronidase requires 5'-flanking
      and intragenic Gus-s sequences.
AB  - Genetics studies of natural variants of the androgen response of mouse beta
      glucuronidase (GUS) reveal a cis-active element closely linked to the GUS
      structural gene (Gus-s) that is necessary for this kidney-specific response.
      Results of our previous studies suggested sequences within or near an androgen
      inducible deoxyribonuclease I-hypersensitive site (DH site) located in the ninth
      intron of Gus-s are associated with the androgen response of GUS. Using
      transgenic mice, we now demonstrate that at least two regions of sequence within
      Gus-s are involved in regulating the androgen response of GUS. The first, located
      within 3.8 kb of Gus-s 5'-flanking sequence, directs the response and its tissue
      specificity, while the second, located within a 6.4-kb fragment of Gus-s
      extending from the third through the ninth intron of Gus-s, protects the androgen
      responsiveness of the transgene from repressive influences of the insertion site.

PMID- 9514152
TI  - Analysis of FKBP51/FKBP52 chimeras and mutants for Hsp90 binding and association
      with progesterone receptor complexes.
AB  - FKBP51, FKBP52, and Cyp40 bind competitively to Hsp90 through their respective
      tetratricopeptide repeat (TPR) domains, and any one of the three immunophilins
      can be isolated in mature steroid receptor complexes. During cell-free assembly
      reactions, FKBP51 associates preferentially with progesterone and glucocorticoid
      receptors, but less preference is observed in FKBP51 association with estrogen
      receptor. A number of mutant FKBP forms were generated to map sequences
      responsible for FKBP51's preferred association with progesterone receptor. A
      double-point mutation in the peptidyl prolyl isomerase domain of FKBP51 that
      reduces enzymatic activity by greater than 90% had no observed effect on FKBP51
      interactions with progesterone receptor or Hsp90. Coprecipitation of FKBP51 and
      FKBP52 truncation mutants with Hsp90 indicated that sequences both upstream and
      downstream of the TPR domain are necessary for Hsp90 binding. FKBP chimeric
      constructs were also generated and tested for Hsp90 binding and receptor
      association. The TPR domain of FKBP51 required appropriate downstream sequences
      for Hsp90 binding, but FKBP52's TPR domain did not. The C-terminal region of
      FKBP51 that functionally interacts with the TPR domain to permit Hsp90 binding
      also conferred preferential association with PR. In conclusion, despite the
      overall similarity of FKBP51 and FKBP52, these two immunophilins associate
      differentially with steroid receptors, and the difference relates to both the
      Hsp90-binding TPR domain and to poorly conserved C-terminal sequences.

PMID- 9514153
TI  - A dual mechanism mediates repression of NF-kappaB activity by glucocorticoids.
AB  - Repression of nuclear factor (NF)-kappaB-dependent gene expression is one of the
      key characteristics by which glucocorticoids exert their antiinflammatory and
      immunosuppressive effects. In vitro studies have shown protein-protein
      interactions between NF-kappaB and the glucocorticoid receptor, possibly
      explaining their mutual repression of transcriptional activity. Furthermore,
      glucocorticoid-induced transcription of IkappaBalpha was presented as a mechanism
      in mediation of immunosuppression by glucocorticoids. At present, the relative
      contribution of each mechanism has not been investigated. We show that
      dexamethasone induced IkappaBalpha gene transcription in human pulmonary
      epithelial A549 cells. However, this enhanced IkappaBalpha synthesis did not
      cause repression of NF-kappaB DNA-binding activity. In addition, dexamethasone
      was still able to inhibit the expression of NF-kappaB target genes
      (cyclooxygenase-2, intercellular adhesion molecule-1) in the absence of protein
      synthesis. Furthermore, we show that the antihormone RU486 did not induce
      IkappaBalpha expression. However, RU486 was still able to induce, albeit less
      efficiently, both glucocorticoid- and progesterone receptor-mediated repression
      of endogenous NF-kappaB target gene expression in A549 cells and the breast
      cancer cell line T47D, respectively. Taken together, these results indicate that
      induced IkappaBalpha expression accounts for only part of the repression of NF
      kappaB activity by glucocorticoids and progestins. In addition, protein-protein
      interactions between NF-kappaB and the glucocorticoid or progesterone receptor,
      resulting in repression of NF-kappaB activity, seem also to be involved. We
      therefore conclude that NF-kappaB activity is repressed via a dual mechanism
      involving both protein-protein interactions and induction of IkappaBalpha.

PMID- 9514154
TI  - Multiple factors interacting at the GATA sites of the gonadotropin-releasing
      hormone neuron-specific enhancer regulate gene expression.
AB  - Neuron-specific expression of the GnRH gene is dependent on an upstream
      multicomponent enhancer. This enhancer is functional in a small population of
      GnRH-producing hypothalamic neurons which, through the secretion of GnRH,
      mediates central nervous system control of reproductive function. GnRH enhancer
      function requires activation by the GATA family of transcription factors that act
      through tandem consensus GATA-binding motifs, GATA-A and GATA-B. Here we show
      that two newly identified DNA-binding factors, termed GBF-A1/A2 and GBF-B1, bind
      the GnRH enhancer at sites overlapping the GATA factor-binding motifs. In vitro
      bindings of GATA, GBF-A1/A2, and GBF-B1 to the GnRH enhancer sequences are
      independent. Specific mutation of either the consensus GATA motif or the GBF-B1
      site of GATA-B does not alter binding of the overlapping factor in vitro.
      Utilizing a GnRH-expressing neuronal cell line as a model system, we show by
      transient transfection that GBF-B1 is necessary for enhancer activity and
      independently activates the GnRH promoter. Transactivation of the GnRH enhancer
      in GT1 cells and in NIH 3T3 cells by GATA-4 is modulated by GBF-B1 binding,
      suggesting GBF-B1 interferes with GATA factor binding through a steric mechanism.

PMID- 9514155
TI  - Testicular GATA-1 factor up-regulates the promoter activity of rat inhibin alpha
      subunit gene in MA-10 Leydig tumor cells.
AB  - We have previously demonstrated that the basal transcription of rat inhibin alpha
      subunit gene in a mouse testicular Leydig tumor cell line, MA-10, depends upon a
      67-bp DNA fragment at the position of -163 to -97. Within this promoter region
      two GATA motifs were observed. In this study, we investigated the possible role
      of GATA-binding proteins in the regulation of inhibin alpha-subunit gene
      transcription in testicular cells. Northern blot and RT-PCR analyses showed that
      mRNAs encoding GATA-binding proteins, GATA-1 and GATA-4, were detected in mouse
      and rat testis and in MA-10 and rat Sertoli cells. Testis-specific GATA-1 mRNA,
      which is transcribed from a promoter 8 kb upstream to the erythroid exon I of
      mouse GATA-1 gene, was also identified in MA-10 cells. Mutations of GATA
      sequences in alpha-subunit promoter markedly decreased the transcriptional
      activity of alpha-subunit gene when measured by their ability of transient
      expression of a bacterial reporter gene, chloramphenicol acetyltransferase (CAT),
      in MA-10 cells. Cotransfection of alphaCAT chimeric construct with cDNA
      expression plasmid coding for mouse GATA-1 or GATA-4 protein revealed that GATA-1
      but not GATA-4 can transactivate alpha-subunit promoter in a dose-dependent
      manner. The transactivation by GATA-1 was inhibited if GATA sequences in alpha
      subunit promoter were mutated. Furthermore, electrophoretic mobility shift assay
      demonstrated that GATA-binding proteins present in nuclear extracts of MA-10
      cells and rat testis interacted with the GATA motifs in alpha-subunit promoter,
      and the GATA-1 in these nuclear extracts formed a supershifted immunocomplex with
      antibody raised against mouse GATA-1 protein. We therefore concluded that the
      basal transcription of inhibin alpha-subunit gene in testicular MA-10 cells is up
      regulated by testicular GATA-1 but not GATA-4 through its interaction with the
      GATA motifs in alpha-subunit promoter. In summary, we have provided the first
      evidence of the functional role of a GATA-binding protein in the regulation of
      testicular gene expression.

PMID- 9514156
TI  - Transcription of the rat serine protease inhibitor 2.1 gene in vivo: correlation
      with GAGA box promoter occupancy and mechanism of cytokine-mediated down
      regulation.
AB  - Two GH-response elements (GHREs) and a single glucocorticoid (GC)-response
      element were found to regulate activity of the rat serine protease inhibitor 2.1
      gene (spi 2.1) promoter in vitro. To assess the physiological relevance of these
      observations, we have investigated the relationship existing between the level of
      spi 2.1 gene transcription, structural modifications of the chromatin, and in
      vivo nuclear protein-promoter interactions monitored by genomic footprinting, in
      control, hypophysectomized, and inflamed rats. We also addressed the mechanism of
      inflammation-mediated gene down-regulation. We found that a high level of spi 2.1
      gene transcription correlates with hypersensitivity of the promoter to
      deoxyribonuclease I (DNase I) and maximal occupancy of the GAGA box (GHRE-I). The
      failure of GAGA-box binding proteins (GAGA-BPs) to interact with the GAGA box
      appears to result from an impairment in GH action due to its absence (i.e.
      hypophysectomized animals) or to the appearance of a cytokine-mediated GH
      resistant state (i.e. inflamed rats) in liver. Unlike the GAGA box, signal
      transducer and activator of transcription (STAT) factor-binding sites included in
      the GHRE-II were never found to be protected against DNase I attack but displayed
      a differential DNase I reactivity depending on the level of gene transcription.
      Alterations in DNase I reactivity of the GC-response element region suggest that
      GC receptor-GC complexes may associate, in a transient manner, with the promoter
      in the actively transcribing control state. Taken together, our studies suggest a
      mechanism of spi 2.1 gene activation in vivo whereby the GH-dependent chromatin
      remodeling caused by or concomitant to the recruitment of GAGA-box binding
      proteins is the first compulsory and presumably predominant step.

PMID- 9514157
TI  - SP1/SP3-binding sites and adjacent elements contribute to basal and cyclic
      adenosine 3',5'-monophosphate-stimulated transcriptional activation of the rhesus
      growth hormone-variant gene in trophoblasts.
AB  - Transcriptional activation of the rhesus monkey GH-variant gene in
      syncytiotrophoblasts is developmentally regulated by trophoblast-specific and
      cAMP-responsive mechanisms. Progressive deletions of 5'-flanking DNA defined the
      most proximal 140 bp as the minimal region retaining full cAMP-stimulated mGH-V
      transcription. To identify the regions of this promoter critical for
      transcription, transient transfections of reporter plasmids containing systematic
      10 base mutations throughout this proximal region were performed. Mutation of the
      region from -140/-131 decreased transcription in syncytiotrophoblasts by 50%, and
      gel mobility-shift analyses demonstrated that Sp1 and Sp3 bound to a region
      containing a GGGAGG motif at -136/-131. Mutation of the -62/-53 region decreased
      transcriptional activation by 66-99%, and Sp1 and Sp3 bound to a GGTGGG motif
      overlapping this region (at -65/-60). Selective mutation of this Sp1/Sp3 site
      decreased basal transcription by approximately 80%, and cAMP-stimulated
      transcription by up to 75% (with the greatest effect in primary
      syncytiotrophoblast cultures), indicating that the Sp1/Sp3 site is critical for
      transcriptional activation. Mutations in the regions adjacent to the Sp1/Sp3
      sites (-130/-111 and -52/-43) also dramatically reduced (by 75%) transcriptional
      activation in trophoblasts. We conclude that two Sp1/Sp3 sites as well as
      additional elements directly adjacent to these sites contribute to trophoblast
      specific cAMP-responsiveness of the mGH-V proximal promoter.

PMID- 9514158
TI  - Identification of trophoblast-specific regulatory elements in the mouse placental
      lactogen II gene.
AB  - Placental lactogen II, the major ligand for the PRL receptor during the second
      half of gestation in rodents, is synthesized specifically by placental
      trophoblast giant cells. A transient transgenic analysis has been used to
      localize the giant cell-specific regulatory region within the mouse placental
      lactogen II gene to sequences between -1340 and -2019 upstream of the
      transcriptional start site. More precise mapping of the regulatory elements has
      been accomplished by transfection of promoter constructs into Rcho-1 trophoblast
      cells, resulting in the characterization of two positive regulatory elements in
      the -1471 to -1340 region; two other regulatory elements have been implicated but
      not further characterized, a negative regulatory element between -2019 and -1778
      and another positive element within the region from -1340 to -569. Both of the
      characterized positive regulatory elements are recognized by factors that are
      enriched in differentiated giant cells compared with proliferative trophoblasts,
      and these factors are either absent or at low levels in fibroblasts. The
      complexes that form on the two elements are distinct and neither element competes
      with the other for factor binding, thus implicating at least two different
      regulatory elements in late-gestational trophoblast giant cell-specific gene
      expression.

PMID- 9514159
TI  - The pan-pituitary activator of transcription, Ptx1 (pituitary homeobox 1), acts
      in synergy with SF-1 and Pit1 and is an upstream regulator of the Lim-homeodomain
      gene Lim3/Lhx3.
AB  - The Ptx1 (pituitary homeobox 1) homeobox transcription factor was isolated as a
      transcription factor of the pituitary POMC gene. In corticotrope cells that
      express POMC, cell-specific transcription is conferred in part by the synergistic
      action of Ptx1 with the basic helix-loop-helix factor NeuroD1. Since Ptx1
      expression precedes pituitary development and differentiation, we investigated
      its expression and function in other pituitary lineages. Ptx1 is expressed in
      most pituitary-derived cell lines and as is the related Ptx2 (Rieger) gene.
      However, Ptx1 appears to be the only Ptx protein in corticotropes and the
      predominant one in gonadotrope cells. Most pituitary hormone-coding gene
      promoters are activated by Ptx1. Thus, Ptx1 appears to be a general regulator of
      pituitary-specific transcription. In addition, Ptx1 action is synergized by cell
      restricted transcription factors to confer promoter-specific expression. Indeed,
      in the somatolactotrope lineage, synergism between Ptx1 and Pit1 is observed on
      the PRL promoter, and strong synergism between Ptx1 and SF-1 is observed in
      gonadotrope cells on the betaLH promoter but not on the alphaGSU (glycoprotein
      hormone alpha-subunit gene) and betaFSH promoters. Synergism between these two
      classes of factors is reminiscent of the interaction between the products of the
      Drosophila genes Ftz (fushi tarazu) and Ftz-F1. Antisense RNA experiments
      performed in alphaT3-1 cells that express the alphaGSU gene showed that
      expression of endogenous alphaGSU is highly dependent on Ptx1 whereas many other
      genes are not affected. Interestingly, the only other gene found to be highly
      dependent on Ptx1 for expression was the gene for the Lim3/Lhx3 transcription
      factor. Thus, these experiments place Ptx1 upstream of Lim3/Lhx3 in a cascade of
      regulators that appear to work in a combinatorial code to direct pituitary-,
      lineage-, and promoter-specific transcription.

PMID- 9514160
TI  - A homozygous microdeletion in helix 7 of the luteinizing hormone receptor
      associated with familial testicular and ovarian resistance is due to both
      decreased cell surface expression and impaired effector activation by the cell
      surface receptor.
AB  - In this report, the genomic DNA was examined from two siblings with gonadal LH
      resistance. A 46,XY pseudohermaphrodite presented with female external genitalia
      and his 46,XX sister exhibited menstrual irregularities (oligoamenorrhea) and
      infertility. Exons 1-11 of the LH receptor (LHR) gene were amplified by the PCR
      using different sets of intronic primers and were directly sequenced. Sequencing
      revealed that both individuals carried a deletion of nucleotides 1822-1827,
      resulting in the deletion of Leu-608 and Val-609 within the seventh transmembrane
      helix. This mutation was introduced into a recombinant human (h) LHR cDNA.
      Transfections of 293 cells with hLHR(wt) vs. hLHR(deltaL608,V609) revealed that
      very little of the mutant receptor was expressed at the cell surface. This was
      due to both a decrease in the total amount of receptor expressed as well as to an
      increased intracellular retention of the mutant receptor. In spite of the
      decreased cell surface expression of the mutant, sufficient amounts were present
      to allow for assessment of its functions. Equilibrium binding assays showed that
      the cell surface hLHR(deltaL608,V609) binds hCG with an affinity comparable to
      that of the wild-type receptor. However, the cells expressing the
      hLHR(deltaL608,V609) exhibit only a 1.5- to 2.4-fold stimulation of cAMP
      production in response to hCG. In contrast, cells expressing comparably low
      levels of hLHR(wt) responded to hCG with 11- to 30-fold increases of cAMP levels.
      Therefore, the testicular and ovarian unresponsiveness to LH in these patients
      appears to be due to a mutation of the hLHR gene in which Leu-608 and Val-609 are
      deleted. As a consequence, the majority of the mutant receptor is retained
      intracellularly. The small percentage of mutant receptor that is expressed at the
      cell surface binds hormone normally but is unable to activate Gs.

PMID- 9514161
TI  - Differential gonadotropin-releasing hormone stimulation of rat luteinizing
      hormone subunit gene transcription by calcium influx and mitogen-activated
      protein kinase-signaling pathways.
AB  - Gonadotropin secretion and gene expression are differentially regulated by
      hypothalamic GnRH pulses by unknown mechanisms. GnRH stimulates calcium influx
      through L-type voltage-gated channels and activates phospholipase C, leading to
      increased protein kinase C (PKC) and mitogen-activated protein kinase activity.
      We found differential contributions of these pathways to GnRH-stimulated rat LH
      subunit transcription in pituitary gonadotropes and cell lines. Endogenous
      transcription of the alpha- and LHbeta-subunits in rat pituitary cells was
      stimulated by GnRH. Independent PKC activation by phorbol myristate acid
      stimulated only the alpha-subunit gene. In contrast, an L-channel antagonist
      (nimodipine) inhibited only LHbeta stimulation by GnRH, and an L-channel agonist
      (BayK 8644) stimulated only basal LHbeta transcription. GnRH induction of a rat
      alpha-subunit promoter construct in alphaT3 cells was unaffected by nimodipine or
      elimination of external calcium, while both treatments eliminated the LHbeta
      response. Application of a mitogen-activated kinase kinase (MEK) inhibitor
      (PD098059) decreased basal and GnRH-stimulated alpha-subunit promoter activity
      and had no effect on LHbeta promoter activity. In pituitary cells from mice
      bearing an LHbeta promoter-luciferase reporter transgene, GnRH stimulation was
      inhibited by nimodipine but not by PD098059. Thus, GnRH induction and basal
      control of the alpha-subunit gene seem to occur through the PKC/mitogen-activated
      protein kinase pathway, while induction of the LHbeta gene is dependent on
      calcium influx. Differential signaling from the same receptor may be a mechanism
      for preferential regulation of transcription.

PMID- 9514162
TI  - Enhanced binding to the molecular chaperone BiP slows thyroglobulin export from
      the endoplasmic reticulum.
AB  - To examine how binding of BiP (a molecular chaperone of the hsp70 family that
      resides in the endoplasmic reticulum) influences the conformational maturation of
      thyroglobulin (Tg, the precursor for thyroid hormone synthesis), we have
      developed a system of recombinant Tg stably expressed in wild-type Chinese
      hamster ovary (CHO) cells and CHO-B cells genetically manipulated for selectively
      increased BiP expression. The elevation of immunoreactive BiP in CHO-B cells is
      comparable to that seen during the unfolded protein response in the thyrocytes of
      certain human patients and animals suffering from congenital hypothyroid goiter
      with defective Tg. However, in CHO-B cells, we expressed Tg containing no
      mutations that induce misfolding (i.e. no unfolded protein response), so that
      levels of all other endoplasmic reticulum chaperones were normal. Increased
      availability of BiP did not accelerate Tg secretion; rather, the export of newly
      synthesized Tg was delayed. Tg detained intracellularly was concentrated in the
      endoplasmic reticulum. By coimmunoprecipitation, BiP exhibited enhanced binding
      to Tg in CHO-B cells. Moreover, two-dimensional gel analysis showed that BiP
      associated especially well with intracellular Tg containing mispaired disulfide
      bonds, thought to represent early Tg folding intermediates. An endoplasmic
      reticulum chaperone of the hsp90 family, GRP94, was also associated in Tg
      chaperone complexes. The results suggest that increased binding of BiP to Tg
      leads to its delayed conformational maturation in the endoplasmic reticulum.

PMID- 9514164
TI  - Hemodynamic disorders in internal thoracic artery: How often are they associated
      with subclavian steal via ipsilateral vertebral artery?
AB  - The scores based on Doppler sonographic spectral features in 14 vertebral
      arteries with flow reversal and 10 vertebral arteries with normal antegrade flow
      were correlated with those of ipsilateral internal thoracic (or internal mammary)
      and subclavian arteries. The statistical analysis revealed significant
      correlation between the scores of all ipsilateral arteries. We concluded that
      color duplex ultrasonographic examination of internal thoracic arteries should be
      carried out in all patients with flow reversal in vertebral arteries. It is
      especially important in those who are potential candidates for coronary
      revascularization using in situ internal thoracic artery graft.

PMID- 9514163
TI  - Fetal intracardiac echogenic foci: does it matter which ventricle?
AB  - We sought to determine whether an association exists between the location of
      intracardiac echogenic foci and fetal aneuploidy or structural cardiac lesions. A
      search of the English language literature since 1980 revealed nine studies
      reporting location of intracardiac echogenic foci, fetal chromosomal
      abnormalities, and cardiac anomalies. Aneuploidy was noted in 10 of 217 fetuses
      with left ventricular and in one of 18 with right ventricular intracardiac
      echogenic foci. Three of 11 fetuses with biventricular intracardiac echogenic
      foci were aneuploid, which is significantly more frequently than when
      intracardiac echogenic foci were present in either ventricle alone (P = 0.02).
      There were nine cases of trisomy 21, four of trisomy 13, and one of trisomy 18.
      Structural cardiac lesions were recognized in eight of 217 fetuses with left
      ventricular foci, two of 18 with right ventricular foci, and one of 11 with
      biventricular intracardiac echogenic foci (P = 0.16). Biventricular intracardiac
      echogenic foci are more frequently associated with fetal aneuploidy but not
      structural lesions, as compared to isolated left or right ventricular
      intracardiac echogenic foci.

PMID- 9514165
TI  - Color Doppler energy: detection of hypoperfused areas in renal transplants.
AB  - The aim of this study was to determine if an area of decreased color on color
      Doppler energy scans in a transplanted kidney could be related to significant
      pathologic conditions. Three hundred and ninety-eight scans in 150 patients were
      thus evaluated prospectively, and 12 such areas were found and correlated to B
      mode, spectral, and color Doppler sonography as well as clinical and laboratory
      findings. A cause for the hypoperfused area was found in all cases; causes
      included two cases of focal infection, four arteriovenous fistulas, one kinking
      of an artery, and five perioperatively severed accessory arteries. We conclude
      that a color Doppler energy evaluation of perfusion differences can be used to
      detect pathologic lesions in a transplanted kidney.

PMID- 9514166
TI  - List of "excuses" from a 20 year veteran sonologist.

PMID- 9514167
TI  - Sonographic evaluation of tears of the gastrocnemius medial head ("tennis leg")
AB  - Rupture of the medial head of the gastrocnemius muscle, or tennis leg, is a
      common lesion affecting middle-aged persons. An imaging examination may be needed
      to rule out other diseases and assess the severity of the tear. We reviewed the
      sonographic images of 65 patients with clinically suspected tennis leg. Fifty-one
      partial and 14 complete tears were diagnosed. Twenty-five patients had follow-up
      examinations (15 days to 24 months; mean, 45 days). The torn muscle fibers,
      hematoma, and the reparative process were appreciated by ultrasonography.
      Ultrasonography may be a useful noninvasive, low-cost modality for diagnosis and
      follow-up of tennis leg.

PMID- 9514168
TI  - Ultrasound interactions with free silicone in a tissue-mimicking phantom.
AB  - This study attempts to explain the physical basis for the sonographic appearance
      of different stages of free silicone in breast tissue by laboratory simulations.
      A tissue-mimicking breast phantom was constructed, into which silicone inclusions
      were introduced, to simulate various forms of silicone leakage within the body.
      These simulations suggest that silicone leakage into surrounding body tissues can
      cause three primary physical interactions with an ultrasound beam: (1)
      distortions due to changes in speed of sound; (2) refraction, causing a "lens"
      effect; and (3) multiple scattering, producing the "snowstorm" effect described
      previously as a signature pattern for detection of silicone migration in breast
      tissue.

PMID- 9514169
TI  - Fetal prognosis in varix of the intrafetal umbilical vein.
AB  - To assess the clinical significance of varix of the intraabdominal portion of the
      umbilical vein, we reviewed 10 cases diagnosed prenatally by ultrasonography at a
      median gestational age of 27 weeks. A comprehensive anatomic survey and serial
      follow-up scans were performed in each case. All three fetuses with associated
      anomalies died in utero, and prenatal karyotyping revealed that two of them had a
      chromosomal abnormality. In six of the seven cases with structurally normal
      fetuses the pregnancy proceeded uneventfully, and no neonatal complications were
      attributed to the umbilical vein varix. Our experience and the review of the
      literature revealed 42 cases with information on fetal outcome. Overall, 24% of
      the fetuses died, 12% had a chromosomal abnormality, and 5% developed hydrops. We
      conclude that fetuses with varix of the intrafetal umbilical vein should be
      considered at risk for poor outcome. However, if no other anomalies are present,
      the prognosis is generally good.

PMID- 9514170
TI  - Prenatal diagnosis of atypical gastroschisis.

PMID- 9514171
TI  - Prostatic abscess due to Aspergillus fumigatus: TRUS and MR imaging findings.

PMID- 9514172
TI  - Prenatal diagnosis of a bifurcating umbilical vein with left iliac vein
      connection.

PMID- 9514173
TI  - Thrombosing umbilical vein varix.

PMID- 9514174
TI  - Terminal myelocystocele: important differential diagnosis in the prenatal
      assessment of spina bifida.

PMID- 9514175
TI  - Release of endogenous nitric oxide mediates arteriolar dilation to endothelin in
      rat striated muscle.
AB  - Previous studies demonstrated that endothelin-1 is a potent vasoconstrictor in
      the microcirculation. In this study, we assessed the ability of endothelin-1 to
      induced dilation of small arterioles in the rat cremaster muscle. Responses to
      topical application of endothelin-1 were assessed by using intravital microscopy.
      Exposure to increasing concentrations of endothelin-1 (10[-13]-10[-8] M) produced
      a dose-dependent constriction of third-order arterioles (20 +/- 1.4 microm).
      Pretreatment with hydroquinone (HQ) or N omega-nitro-L-arginine methyl ester (L
      NAME), antagonists of nitric oxide production, caused a significant potentiation
      in the reactivity of third-order arterioles to endothelin-1. In addition, we
      observed a significant vasodilation to low levels of endothelin-1 (10[-14]-10[
      12] M) in the presence of the endothelin type-A receptor (ET-A) antagonist,
      BQ123. This dilation was abolished in the presence of a 10(-4) M bath
      concentration of L-NAME. These results indicated that endothelin-1 caused
      arteriolar dilation by stimulating endogenous production of nitric oxide. This
      effect appeared to attenuate the constrictor effects of endothelin-1 on small
      resistance vessels in striated muscle.

PMID- 9514176
TI  - Effects of dichloroacetate on mechanical recovery and oxidation of physiologic
      substrates after ischemia and reperfusion in the isolated heart.
AB  - The effects of dichloroacetate (DCA) on fatty acid oxidation and flux through
      pyruvate dehydrogenase (PDH) were studied in ischemic, reperfused myocardium
      supplied with glucose, long-chain fatty acids, lactate, pyruvate, and
      acetoacetate. The oxidation rates of all substrates were determined by combined
      13C nuclear magnetic resonance (NMR) spectroscopy and oxygen-consumption
      measurements, and PDH flux was assessed by lactate plus pyruvate oxidation. In
      nonischemic control hearts, DCA increased PDH flux more than eightfold (from 0.68
      +/- 0.28 to 5.81 +/- 1.16 micromol/min/g dry weight; n = 8 each group; p < 0.05)
      and significantly inhibited the oxidation of acetoacetate and fatty acids. DCA
      also improved mechanical recovery after 30 min of ischemia plus 30 min of
      reperfusion but did not significantly increase PDH flux measured at the end of
      the reperfusion period (1.35 +/- 0.42 micromol/min/g dry weight) compared with
      untreated ischemic hearts (0.87 +/- 0.28 micromol/min/g dry weight; n = 8 each
      group; p = NS). Although DCA had a modest effect on functional recovery in the
      reperfused myocardium, this beneficial effect was not associated with either
      marked stimulation of PDH flux or inhibition of fatty acid oxidation.

PMID- 9514177
TI  - Melagatran, an oral active-site inhibitor of thrombin, prevents or delays
      formation of electrically induced occlusive thrombus in the canine coronary
      artery.
AB  - Intravenous administration of thrombin inhibitors, such as hirudin, has been
      shown to decrease the frequency of coronary artery reocclusion after
      thrombolysis. However, recent findings in large clinical trials in patients with
      unstable angina and myocardial infarction have failed to demonstrate a sustained
      antithrombotic effect after cessation of drug treatment. These findings indicate
      a need for a prolonged antithrombotic regimen, preferably an orally active
      thrombin inhibitor. To test the hypothesis that a regimen consisting of oral
      thrombin inhibitor will delay or prevent the formation of occlusive clot,
      anesthetized dogs were given saline (n = 9) or a single dose of a novel active
      site low-molecular-weight thrombin inhibitor melagatran by nasogastric tube (1.5
      mg/kg, n = 6; 2.5 mg/kg, n = 6), and 15 min later, a potent thrombogenic stimulus
      in the form of anodal current (100 microA) was applied to the intimal surface of
      the narrowed left anterior descending coronary artery (LAD). All saline-treated
      dogs developed stable thrombus, indicated by zero flow at 34 +/- 7 min after
      initiation of direct current. On the other hand, one of the six dogs given high
      dose melagatran did not develop thrombotic occlusion of the LAD during the entire
      4 h of observation. Mean time to occlusive thrombus formation in 11 other dogs
      was prolonged 4-5 times as compared with that in the saline-treated dogs (p <
      0.001). Spontaneous thrombolysis was observed in three of 11 dogs after initial
      clot formation. Overall, the coronary artery was patent for 68% (low dose) and
      75% (high dose) of the observation period in melagatran-treated dogs (vs. 14% of
      observation period in saline-treated dogs). Peak plasma concentration was 0.87 +/
      0.22 microM in dogs given low-dose and 1.38 +/- 0.30 microM in dogs given high
      dose melagatran. The activated partial thromboplastin time (aPTT) increased 1.5
      fold at peak plasma concentration of melagatran. These observations imply (a)
      thrombin generation plays a critical role in thrombus formation in narrowed
      coronary arteries, (b) oral melagatran prevents or delays thrombus formation,
      whereas the aPTT is only modestly prolonged, and (c) the thrombus formed in the
      presence of melagatran is prone to spontaneous lysis in this canine model of
      coronary thrombosis.

PMID- 9514178
TI  - Effect of aging on A1-adenosine receptor-mediated inhibition of norepinephrine
      release in the rat heart.
AB  - Adenosine inhibits norepinephrine (NE) release from cardiac adrenergic nerves and
      reduces the postsynaptic beta-adrenergic mediated actions of NE, leading to
      decreased myocardial force of contraction. The actions of adenosine are mediated
      by pre- and postsynaptic adenosine A1 receptors (A1-AdoR). We reported that
      adenosine inhibition of postsynaptic beta-adrenergic receptor-mediated cyclic
      adenosine monophosphate (cAMP) production declines with age in male F344 rat
      hearts. In this study, cardiac synaptosomes, isolated intact adrenergic nerve
      terminals, were used to examine the effect of age on adenosine inhibition of NE
      release. Cardiac synaptosomes were prepared from the hearts of 6- and 24-month
      old male F344 rats, loaded with [3H]NE, and placed in a superfusion system.
      [3H]NE release was induced by high [K+] exposure in the presence of varying
      concentrations of adenosine or the specific A1-AdoR agonist, N6-p
      sulfophenyladenosine (SPA). [3H]NE release was significantly reduced in old rats
      compared with young rats. Inhibition of [3H]NE release by adenosine and SPA was
      significantly greater in young rats compared with old rats. The A1-AdoR
      antagonist, 8-(p-sulfophenyl)-theophylline, blocked the actions of adenosine on
      [3H]NE release, and the specific adenosine A2-receptor agonist,
      cyclopropylcarboxamidoadenosine, had no effect on [3H]NE release. Our data
      suggest that presynaptic A1-AdoR-mediated inhibition of NE release in the rat
      heart declines with age.

PMID- 9514180
TI  - Long-term effects of cicletanine on secondary pulmonary hypertension.
AB  - Cicletanine, a furopyridine-derivative drug, was shown to enhance the production
      of endogenous prostacyclin. The potent vasodilating properties of prostacyclin
      are used to treat severe primary pulmonary hypertension. Prostacyclin has a short
      half-life and can be administered only as an i.v. infusion. The aim of this study
      was to evaluate the effects of cicletanine on pulmonary artery hypertension (PAH)
      resulting from chronic obstructive lung disease (COLD). In a double-blind
      controlled study, we evaluated the effects of short- and long-term administration
      of cicletanine (50 mg daily, orally) on hemodynamics and blood gases of patients
      with PAH resulting from COLD. The initial dose of 50 mg of cicletanine had no
      effect. A significant decrease in the mean pulmonary artery pressure (15%) and in
      total pulmonary resistance (20%) was observed after 3 or 12 months of treatment
      in the cicletanine group (11 patients), when compared with placebo (12 patients).
      PaO2 decreased slightly in the cicletanine group, but the difference from the
      control group was not significant. These results suggest that long-term treatment
      with cicletanine can induce effective pulmonary vasodilation in patients with PAH
      caused by COLD and that this is probably responsible for a small venous
      admixture.

PMID- 9514179
TI  - Right-shifting the oxyhemoglobin dissociation curve with RSR13: effects on high
      energy phosphates and myocardial recovery after low-flow ischemia.
AB  - RSR13[2-(4[[(3,5-Dimethylanilino)carbonyl] methyl] phenoxy)-2-methyl propionic
      acid], a synthetic allosteric modifier of hemoglobin, increases O2 release from
      hemoglobin at low oxygen tension. The isolated blood-perfused rat heart was
      examined during potassium-arrest to determine the effects of RSR13 on the
      concentration of phosphocreatine (PCr) and adenosine triphosphate (ATP) by using
      31P nuclear magnetic resonance (NMR) spectroscopy throughout an episode of low
      flow ischemia. All hearts were perfused at constant flow during control (2.0
      ml/min) and low-flow (0.2 ml/min) conditions. In normoxic hearts, RSR13 had no
      effect on either the 31P NMR spectrum or the rate-pressure product. In hearts
      subjected to 30 min of reduced flow, treatment with RSR13 improved mechanical
      function on reperfusion (p = 0.026 after 20 min; p = 0.032 after 25 min; and p =
      0.045 after 30 min) at 2.0 ml/min with normokalemic blood perfusate. In potassium
      arrested hearts, the rate of decrease of [ATP] was reduced in hearts exposed to
      RSR13 (p < or = 0.05 between 10 and 35.8 min of ischemia except at 28.4 min)
      during low flow. These results indicate a protective effect of RSR13 on high
      energy phosphates during low-flow ischemia and mechanical recovery after
      reperfusion.

PMID- 9514181
TI  - Mechanisms underlying the neurogenic relaxation in dog isolated hepatic arteries.
AB  - In canine hepatic arterial strips responding to nicotine with contraction,
      prazosin abolished the response or reversed it to a relaxation. Mechanisms
      underlying the relaxation were analyzed in hepatic and coronary arterial strips
      denuded of the endothelium and treated with prazosin and indomethacin. In the
      hepatic arterial strips precontracted with prostaglandin (PG) F2alpha, nicotine
      induced relaxations were not influenced by atropine but were inhibited by timolol
      and abolished by hexamethonium. Treatment with [8-37] calcitonin gene-related
      peptide ([8-37] CGRP), a selective CGRP1-receptor antagonist, also attenuated the
      nicotine-induced relaxation, but a vasoactive intestinal polypeptide antagonist
      was without effect. Combined treatment with timolol and [8-37] CGRP depressed the
      response to a greater extent than either antagonist alone. The slight relaxation
      remaining under the combined treatment was abolished by NG-nitro-L-arginine (L
      NA) and restored by L-arginine. In coronary arterial strips precontracted with
      PGF2alpha, nicotine produced a moderate relaxation, which was abolished or
      markedly inhibited by treatment with hexamethonium or timolol but was unaffected
      by L-NA. It is concluded that the nicotine-induced relaxation is mediated by
      norepinephrine, CGRP, and NO released from perivascular nerves in dog hepatic
      arterial strips; the responses associated with activations of beta-adrenoceptors
      and CGRP1 receptors are predominant over those to NO. The coronary arterial
      relaxation seems to be mediated by neurogenic norepinephrine but not by NO.

PMID- 9514182
TI  - Endothelium-independent relaxation and hyperpolarization to C-type natriuretic
      peptide in porcine coronary arteries.
AB  - Endothelial cells produce C-type natriuretic peptide (CNP), which has been
      proposed as an endothelium-derived hyperpolarizing factor. In porcine coronary
      arteries, we investigated the vasodilatory effects of CNP and compared them with
      endothelium-dependent relaxations and hyperpolarizations to bradykinin. Isolated
      epicardial porcine coronary arteries were studied in organ chambers, and
      concentration-response curves to CNP and bradykinin were obtained. Membrane
      potential was measured in endothelial cells and smooth muscle of intact porcine
      coronary arteries during stimulation with CNP or bradykinin. In precontracted
      porcine coronary arteries with or without endothelium, CNP (10[-10]-10[-6] M)
      evoked relaxations (maximum, 42 +/- 4%) smaller than those evoked by bradykinin
      (100 +/- 1%), blunted in preparations contracted by KCl instead of U46619 (9,11
      dideoxy-11a,9a-epoxymethano-prostaglandin F2alpha; p < 0.05) and unaffected by
      inhibition of NO synthase (NS). CNP evoked hyperpolarization of vascular smooth
      muscle of similar magnitude in endothelium-intact (-4.4 +/- 1 mV) and endothelium
      denuded (-4.6 +/- 1 mV) porcine coronary arteries. Bradykinin (10[-10]-10[-6] M)
      evoked concentration-dependent relaxations in preparations with endothelium only.
      Although atrial natriuretic peptide-receptor antagonist HS-142-1 (25 microM)
      slightly reduced the sensitivity to bradykinin (log shift at IC50, twofold; p <
      0.05), it had no effect on the maximal response to bradykinin. Inhibition of NO
      synthase partially attenuated, whereas high potassium chloride (30 mM) markedly
      inhibited relaxations to bradykinin (p < 0.05). Hyperpolarization to bradykinin
      was much more pronounced than that to CNP (-17 +/- 3 mV; p < 0.05 vs. CNP) and
      was observed in endothelium-intact preparations only and unaffected by HS-142-1.
      In conclusion, in contrast to bradykinin, CNP induces endothelium-independent and
      weaker relaxation and hyperpolarization of coronary artery vascular smooth
      muscle, suggesting that CNP is an unlikely mediator of endothelium-dependent
      hyperpolarization of porcine coronary arteries.

PMID- 9514183
TI  - Antihypertensive effectiveness of a very low fixed-dose combination of moexipril
      and hydrochlorothiazide.
AB  - The antihypertensive and metabolic effects of a fixed combination of very low
      dose of moexipril (MO), an angiotensin-converting enzyme (ACE) inhibitor, and
      hydrochlorothiazide (HCTZ) were tested in a multicenter, placebo (PBO)
      controlled, double-blind, parallel study of men (M) and women (W) with mild to
      moderate essential hypertension. After 4 weeks of PBO treatment, 223 patients
      with sitting diastolic blood pressure (SDBP) of 95-114 mm Hg and sitting systolic
      blood pressure (SSBP) < or =200 mm Hg, inclusive, were randomized to PBO (114
      patients: M, 56; W, 58) and MO/HCTZ 3.75/6.25 mg (109 patients: M, 58; W, 51)
      given once daily and followed up for 12 weeks. The fixed combination MO/HCTZ,
      3.75/6.25 mg, reduced SSBP/SDBP -7.6/-7.6 mm Hg (M, -8.5/-8.0; W, -6.3/-7.0),
      versus PBO, +0.2/-3.9 mm Hg (M, -1.9/-3.4; W, +1.1/-4.4); p < 0.05. Also, 54% of
      patients receiving MO/HCTZ, 3.75/6.25 mg/day, had good blood pressure response
      (SDBP < or =90 mm Hg, or > or =10 mm Hg decrease from baseline), versus 28% for
      PBO (p < 0.001). The clinical and metabolic side effects were minor and not
      different between MO/HCTZ and PBO. The results of this study indicate (a) a once
      daily very low dose fixed combination of MO/HCTZ is effective and well tolerated
      by men and women with mild to moderate essential hypertension; (b) it is almost
      devoid of clinical and metabolic side effects; and (c) the safety profile was
      similar in men and women.

PMID- 9514184
TI  - Mechanisms of hemodynamic responses to cocaine in conscious rats.
AB  - Several agents have been used to treat cocaine-related cardiovascular
      complications and toxicity occurring in sensitive individuals, yet the causes of
      hemodynamic responsiveness and differential sensitivity to cocaine are unknown.
      In this study, we sought to examine the role of different mediators in a model of
      variable cardiovascular responses to cocaine. As noted previously in conscious
      rats, cardiac output (CO) and systemic vascular resistance (SVR) responses to
      cocaine (5 mg/kg, i.v.) varied widely. Twenty of 34 rats exhibited cocaine
      induced decreases in CO of > or =8% and large increases in SVR (designated
      vascular responders). The remaining rats with little change or an increase in CO
      and smaller increases in SVR were named mixed responders. Pretreatment with
      propranolol (1 mg/kg) or metoprolol (1 mg/kg) reduced heart rate. In mixed
      responders, propranolol or metoprolol reversed the cocaine-induced increase in CO
      and stroke volume and enhanced the increase in SVR, making these rats respond
      like vascular responders. Nicardipine (25 microg/kg) reduced the pressor response
      and selectively reversed the CO responses in vascular responders. N omega-nitro-L
      arginine methyl ester (L-NAME; 2.7 mg/kg) increased arterial pressure by
      increasing SVR. Cocaine induced greater pressor and SVR responses apparently
      because of a shift in baseline values elicited by L-NAME alone. Therefore,
      differences in hemodynamic responses patterns may be the result of differences in
      beta-adrenergic activation or subsequent calcium channel activation or both. We
      predict that calcium channel antagonists may be useful to treat cocaine-induced
      cardiovascular complications, whereas beta-adrenergic antagonists are not likely
      to be beneficial.

PMID- 9514185
TI  - CP-060S, a novel cardioprotective drug, limits myocardial infarct size in
      anesthetized dogs.
AB  - The myocardial infarct size (IS)-limiting effect of CP-060S, a novel
      cardioprotective drug that prevents Na+-, Ca2+-overload and has Ca2+ channel
      blocking activity, was compared with that of diltiazem, a pure Ca2+ antagonist,
      to determine whether the prevention of Na+-, Ca2+-overload contributes to this IS
      limiting effect. Dogs were subjected to 90 min of left circumflex coronary artery
      (LCx) occlusion followed by 5 h of reperfusion. Either CP-060S (300 microg/kg) or
      diltiazem (600 microg/kg) was administered intravenously 20 min before the
      occlusion. CP-060S significantly limited IS compared with that of vehicle
      (percentage of the area at risk: vehicle, 50.64 +/- 6.08%; CP-060S, 21.13 +/-
      3.75%; p < 0.01 vs. vehicle). Although diltiazem exerted a significant decrease
      in rate-pressure product (RPP; an index of myocardial oxygen consumption) during
      occlusion equal to that of CP-060S, diltiazem did not significantly reduce IS
      (33.90 +/- 4.30%). Regional myocardial blood flow (RBF) was not significantly
      different between any of the groups. Therefore the IS-limiting effect of CP-060S
      cannot be explained in terms of changes in RPP or RBF. Thus the IS limitation
      induced by CP-060S is probably the consequence of a direct cardioprotective
      effect on myocytes. The prevention of Na+-, Ca2+-overload may be the primary
      reason for this IS-limiting effect.

PMID- 9514186
TI  - Effects of MDL 100,240, a dual inhibitor of angiotensin-converting enzyme and
      neutral endopeptidase on the vasopressor response to exogenous angiotensin I and
      angiotensin II challenges in healthy volunteers.
AB  - MDL 100,240, a dual inhibitor of angiotensin-converting enzyme (ACE) and neutral
      endopeptidase (NEP), was administered intravenously to two panels of four healthy
      males in a four-period, dose-increasing (0, 1.56, 6.25, and 25 mg, and 0, 3.13,
      12.5, and 50 mg, respectively) double-blind, placebo-controlled study. Plasma ACE
      activity and blood-pressure response to exogenous angiotensin I and angiotensin
      II i.v. challenges and safety and tolerance were assessed over a 24-h period. MDL
      100,240 induced a rapid, dose-related, and sustained inhibition of ACE (>70% over
      24 h at doses > or =12.5 mg). The time integral of ACE inhibition was related to
      the dose but with near-maximal values already attained at doses > or =12.5 mg.
      Systolic and diastolic blood-pressure responses to exogenous angiotensin I
      challenges were inhibited in a dose-dependent fashion, whereas the effects of
      angiotensin II remained unaffected. Mean supine blood pressure decreased
      transiently (3 h) at doses > or =3.125 mg and < or =24 h with the 25- and 50-mg
      doses, but not significantly. MDL 100,240 was well tolerated. In healthy
      subjects, MDL 100,240 exerts a dose-dependent and long-lasting ACE-blocking
      activity, also expressed by the inhibition of the pressor responses to exogenous
      angiotensin I challenges. The baroreceptor reflex, assessed by the response to
      exogenous angiotensin II challenge, remains unaltered.

PMID- 9514187
TI  - Lack of involvement of mast cell degranulation in the antiarrhythmic effect of
      preconditioning in rats.
AB  - It has been proposed that the cardioprotective effects of myocardial ischaemic
      preconditioning may involve the release of mast cell mediators. The aim of the
      study was to determine whether mast cells are involved in the antiarrhythmic
      effect of ischaemic preconditioning in rat hearts. Preconditioning was achieved,
      both in anaesthetised rats and in rat isolated hearts, by a 3-min temporary
      occlusion of the left main coronary artery followed by 10 min of reperfusion
      before a 30-min permanent occlusion. Preconditioning had a marked antiarrhythmic
      effect, reducing the number of ventricular ectopic beats from 1,176 +/- 69 to 490
      +/- 139 and the incidence of ventricular fibrillation from 40% to 0.
      Administration of the mast cell-stabilising drugs lodoxamide tromethamine and
      sodium cromoglycate (20 mg/kg/h i.v. 30 min before and throughout experimental
      protocol) did not modify the antiarrhythmic effect of preconditioning. Sodium
      cromoglycate, but not lodoxamide tromethamine, itself significantly reduced the
      number of ectopic beats that occurred over a 30-min period of ischaemia (from 760
      +/- 181 to 153 +/- 33 in nonpreconditioned animals). Both drugs abolished the
      decrease in arterial blood pressure that occurred on coronary artery occlusion.
      The decrease in arterial blood pressure produced by the mast cell-degranulating
      compound 48/80 (50 microg/kg; i.v.) was attenuated to a similar degree by both
      drugs (decreases in pressure of 53 +/- 7, 31 +/- 1, and 25 +/- 3 mm Hg in
      control, sodium cromoglycate-treated, and lodoxamide tromethamine-treated
      animals, respectively). In rat isolated hearts, degranulation of mast cells with
      three consecutive doses of 50 microg of compound 48/80 had no antiarrhythmic
      effects and did not modify the antiarrhythmic effect of preconditioning. It is
      concluded that cardiac mast cells do not play a major role in the protection
      offered by ischaemic preconditioning on arrhythmogenesis in rat hearts.

PMID- 9514188
TI  - Evidence using immunoelectron microscopy for regulated and constitutive pathways
      in the transport and release of endothelin.
AB  - We investigated the distribution of endothelin (ET)-like immunoreactivity in the
      human coronary artery and examined sites linked to the storage and release of
      intracellular proteins. Intense ET-like immunoreactivity was observed at the
      light-microscope level in luminal coronary artery endothelial cells. A low level
      of staining also was detected in the outer medial smooth-muscle layer and
      diffusely within the adventitia. Immunoelectron microscopy was used to determine
      the ultrastructural localisation of ET in the endothelium. Positive ET-like
      immunoreactive staining was detected in secretory vesicles at the ultrastructural
      level. Quantitative immunoelectron microscopy revealed that ET-like
      immunoreactivity was predominantly localised to the cytoplasmic matrix (including
      secretory vesicles) and Weibel-Palade bodies (endothelial cell-specific storage
      granules). Labelling was detected in 44% of Weibel-Palade body profiles
      positively identified by using antisera to von Willebrand factor and in cytoplasm
      surrounding these structures. A low level of immunoreactive staining was
      associated with mitochondria, whereas the cell nucleus and Golgi complex showed
      little or no positive staining. These findings indicate that ET is released from
      human coronary artery endothelial cells via two distinct secretory pathways. We
      propose that ET is continuously transported in and released from secretory
      vesicles by the constitutive secretory pathway. ET may also be stored in Weibel
      Palade bodies and released after an appropriate stimulus by the regulated
      pathway. Positive immunoreactivity was also observed in plasmalemmal vesicles (50
      to 60-nm diameter), indicating a role for these structures in endocytosis.

PMID- 9514189
TI  - Time course of a new ultrashort-acting beta-adrenoceptor-blocking drug, ONO-1101:
      comparison with those of esmolol and propranolol by using the canine isolated,
      blood-perfused heart preparations.
AB  - Time courses of beta-adrenoceptor-blocking actions of ONO-1101, a new
      cardioselective beta-blocker, were compared with those of esmolol and propranolol
      by using the isolated, blood-perfused sinoatrial node (SAN) and papillary muscle
      (PM) preparations of dogs. ONO-1101 per se given intraarterially (i.a.) in each
      nutrient artery did not affect basal sinoatrial rates (SARs; 99 +/- 2 beats/min,
      n = 7) in the SAN and developed tension (DT; 3.2 +/- 0.7 g, n = 7) of the PM
      preparations. Norepinephrine (NE) injected i.a. into the each artery induced
      increases in SAR (42 +/- 6 beats/min at 0.051 +/- 0.014 microg) and PMDT (2.9 +/-
      0.4 g at 0.048 +/- 0.011 microg). The i.a. injections of NE were repeated every 3
      min after i.v. bolus injections of ONO- 1101 into the support dog. NE-induced
      increases in SAR and PMDT were maximally inhibited 3 to 6 min after the i.v.
      injections of ONO-1101. Maximal percentage inhibitions by ONO-1101 of NE-induced
      increases in SAR were 54 +/- 6, 78 +/- 3, and 96 +/- 2% at 0.01, 0.1, and 1 mg/kg
      of the drug, respectively. Similarly, maximal percentage inhibitions by ONO-1101
      of NE-induced increases in PMDT were 50 +/- 12, 93 +/- 2, and 100% +/- 0,
      respectively. The inhibition was quickly recovered; times required for 50%
      recovery (RT1/2) were 12 +/- 3. 17 +/- 3, and 32 +/- 10 min in the SAN
      preparation, and 13 +/- 3, 16 +/- 2, and 39 +/- 11 min in the PM preparations,
      after i.v. injections of 0.01, 0.1, and 1 mg/kg of ONO-1101, respectively. In
      comparison, maximal percentage inhibitions by esmolol of NE-induced increases in
      SAR were 45 +/- 5, 79 +/- 6, and 96 +/- 2%, and those in PMDT were 34 +/- 4, 75
      +/- 5, and 97 +/- 1%, whereas the RT1/2 values were 11 +/- 2, 15 +/- 4, and 40 +/
      12 min in the SAN preparation, and 10 +/- 2, 16 +/- 7, and 27 +/- 6 min in the
      PM preparations, after i.v. injections of 0.01, 0.1, and 1 mg/kg of esmolol,
      respectively. In contrast, the maximal percentage inhibitions by an i.v. bolus
      injection of 0.1 mg/kg of propranolol of NE-induced increases in SAR and PMDT
      were 77 +/- 18% and 87 +/- 13% (n = 4). respectively. The maximal inhibitions
      were obtained 6-15 min after injections of propranolol and then slowly recovered
      only by 21% in the SAN and 8% in the PM preparations, even after 60 min. These
      results clearly demonstrate that ONO-1101 is an ultrashort-acting beta-blocker,
      but the recovery time is dose dependent, and that the beta-blocking action of ONO
      1101 is almost similar to or slightly more potent (or both) than esmolol.

PMID- 9514190
TI  - Intravenous and oral antiplatelet/antithrombotic efficacy and specificity of
      XR300, a novel nonpeptide platelet GPIIb/IIIa antagonist.
AB  - Currently used antiplatelet drugs including aspirin, ticlopidine, and others are
      effective against certain but not all of the many endogenous platelet activators.
      Because of their limited efficacy, a significant number of serious thromboembolic
      complications still occur, highlighting the need for a more effective therapy.
      Thus our study was undertaken to define the antiplatelet efficacy, specificity,
      and the intravenous and oral antiplatelet/antithrombotic effects of a nonpeptide
      glycoprotein alphaIIb beta3 integrin (GPIIb/IIIa) antagonist XR300, an ethyl
      ester prodrug of XR299. XR300, on its conversion to the active form XR299,
      inhibited human platelet aggregation induced by 100 microM adenosine diphosphate
      (ADP) with a median inhibitory concentration (IC50) of 0.09 microM. Similarly,
      XR299 inhibited 125I-fibrinogen binding to human gel-purified platelets (IC50,
      0.01 microM) regardless of the agonist used. In purified human GPIIb/IIIa, XR299
      demonstrated a competitive high-affinity binding with an IC50 of 1.2 nM. XR299
      demonstrated a high degree of specificity for platelet GPIIb/IIIa (alphaIIb
      beta3) as compared with other integrins including alpha(v)beta3, alpha(v)beta5,
      and alpha4beta1, where IC50 values were >10 microM. XR300 administered to mongrel
      dogs either intravenously (0.5-1.0 mg/kg, i.v.) or orally at 1.0-2.0 mg/kg,
      demonstrated maximal antiplatelet effects with rapid onset and extended duration.
      XR300 demonstrated maximal antithrombotic efficacy in preventing the incidence of
      occlusive thrombosis or cyclic flow reduction (CFR) in the carotid or femoral
      artery thrombosis models induced either electrolytically or by mechanical injury
      along with stenosis. In conclusion, XR300 is a novel intravenous and oral
      antiplatelet/antithrombotic agent with high affinity and specificity for platelet
      GPIIb/IIIa receptors.

PMID- 9514191
TI  - Prevention of acute inducible atrial flutter in dogs by using an ibutilide
      polymer-coated pacing electrode.
AB  - Atrial arrhythmias (atrial fibrillation or atrial flutter) after coronary artery
      bypass graft surgery are difficult to prevent or treat and often result in
      significant morbidity. Prior experimental studies by our group showed improved
      therapeutic efficacy for antiarrhythmic drugs delivered via controlled-release
      polymeric matrices implanted on the epicardial surface. These experiments were
      conducted to test the hypothesis that direct atrial epicardial administration of
      ibutilide from a controlled-release system (compared with intravenous
      administration) can reduce the inducibility of atrial flutter in the acute
      postoperative atrial myocardium. Polymeric sustained-release preparations were
      formulated by solvent casting of an ibutilide and polyurethane (Pellathane)
      solution in tetrahydrofurane. Multilayer solvent-casted coatings on pacing
      electrode wires were carried out to fabricate a sustained-release electrode
      system. In animal model studies, each dog underwent a thoracotomy, followed by a
      right atriotomy that was repaired. Induction of atrial flutter was attempted by
      burst pacing with the bipolar pacing catheter. Sinus rhythm was restored with
      overdrive pacing. After determining the induction rate (percentage) of atrial
      flutter in the baseline state, a stainless-steel wire coated with the drug
      delivery system, 10% ibutilide/90% polyurethane (n = 7), or without drug
      (polyurethane coating without ibutilide, n = 5; control) was sewn onto the right
      atrium. Systemic intravenous administration of ibutilide (1.2 microg/kg/h) also
      was carried out in a separate group of animals after atriotomy (n = 5). For
      ibutilide (at an estimated dose of 1.2 microg/kg/h), the atrial-flutter results
      were 41.85 +/- 2.21% induction for baseline compared with 12.42 +/- 5.26% (p =
      0.02) after the ibutilide wire implant. In the control dogs, atrial flutter was
      induced 29.4 +/- 4.7% at baseline and 25.2 +/- 5.1% after implantation of the
      control wire (p = 0.4). Ibutilide coronary venous serum concentrations at the end
      of the ibutilide-polyurethane electrode experiments were 2.25 +/- 0.2 ng/ml (mean
      +/- SEM) versus systemic levels that were below the limits of detection. Systemic
      intravenous ibutilide infusions had no effect on the inducibility of atrial
      flutter. In conclusion, an epicardial implantable electrode coating with an
      ibutilide controlled drug-release system significantly reduced the inducibility
      of atrial flutter in an experimental atriotomy model. These results suggest that
      atrial arrhythmias occurring after coronary bypass surgery may be prevented by
      local atrial administration of ibutilide from a controlled-release pacing
      electrode.

PMID- 9514192
TI  - Effect of Ginkor Fort on hypoxia-induced neutrophil adherence to human saphenous
      vein endothelium.
AB  - This study was performed to evaluate the effects of Ginkor Fort, a venotropic
      drug composed of Ginkgo biloba extract, troxerutine, and heptaminol, on
      neutrophil adherence to the endothelium of saphenous veins. When saphenous veins
      were incubated 2 h in hypoxic conditions, they showed a five- to sixfold increase
      in neutrophil adherence to the endothelium. Ginkor Fort at 0.3 mg/ml was able to
      inhibit this increase by 69%. These results were confirmed by observations in
      scanning electron microscopy. Ginkor Fort also inhibited the subsequent
      activation of these neutrophils, as evidenced by the inhibition of superoxide
      anion release. The biochemical mechanism of this inhibition of neutrophil
      adherence was studied on endothelial cells in culture. We observed that Ginkor
      Fort was able to inhibit the different steps of the activation of endothelial
      cells by hypoxia: the activation of phospholipase A2 and the decrease in
      adenosine triphosphate (ATP) content. By preventing the first step of the
      activation cascade, the decrease in ATP content, Ginkor Fort blocks the
      subsequent increase in neutrophil adherence as well as neutrophil activation. The
      biochemical mechanism evidenced in this work might explain the beneficial effect
      of this drug in the treatment of patients with chronic venous insufficiency.

PMID- 9514193
TI  - Role of AT1 and AT2 receptors in the plasma clearance of angiotensin II.
AB  - This study assessed the role of angiotensin (Ang) AT1 and AT2 receptors as
      modulators of the plasma clearance of Ang II. Groups of male spontaneously
      hypertensive rats (SHRs; n = 25) were given an intravenous injection of either
      saline, losartan, PD123319, losartan in combination with PD123319, or Sar1-Thr8
      Ang II. One hour later, Ang II (0.5 microg/kg) was infused for 15 min into a
      vein. Immediately thereafter, arterial blood samples were collected at regular
      intervals for the assay of plasma Ang II levels by radioimmunoassay. The infusion
      of Ang II significantly increased baseline mean arterial pressure (MAP) in rats
      pretreated with either saline or PD123319 but not in those receiving losartan,
      losartan combined with PD123319, or Sar1-Thr8-Ang II. The plasma clearance of Ang
      II was significantly greater in rats injected with either PD123319, losartan
      combined with PD123319, or Sar1-Thr8-Ang II compared to those injected either
      saline or losartan. Furthermore, the half-life of Ang II in rats pretreated with
      saline or losartan was significantly greater than that measured in the other
      three groups. These results suggest that plasma clearance of Ang II in the SHRs
      is independent of an AT1 receptor, but plasma levels of the peptide are
      unexpectedly protected by an AT2 receptor-dependent mechanism.

PMID- 9514194
TI  - Antithrombotic action of TA-993, a new 1,5-benzothiazepine derivative, in a
      canine model of femoral arterial thrombosis.
AB  - TA-993 is a novel 1,5-benzothiazepine derivative of l-cis configuration, having a
      potent antiplatelet action and an increasing action on femoral blood flow. We
      evaluated the antithrombotic effect of TA-993 in a canine model of femoral
      arterial thrombosis. Thrombus was induced by both application of direct anodal
      current to the femoral artery and partial occlusion of the artery. The partial
      occlusion by placing an adjustable occluder on the artery and the current
      application were carried out 40 and 60 min after the intraduodenal administration
      of drugs, respectively. In control dogs, complete sustained occlusion of the
      femoral artery due to thrombus occurred 55.4 +/- 9.2 min after the onset of
      current application. TA-993 (3 and 10 mg/kg) dose-dependently prolonged the time
      for occlusion. Aspirin (30 mg/kg) also prolonged it. TA-993, 10 mg/kg,
      significantly inhibited whole-blood aggregation 60 min after the administration
      with a weaker potency than that of aspirin (30 mg/kg), whereas 3 mg/kg of TA-993
      did not. The inhibitory effect of TA-993 (10 mg/kg) on platelet aggregation was
      maintained for >7 h. Moreover, TA-993 (10 mg/kg) increased femoral blood flow in
      spite of the partially occluded condition. These results indicate that TA-993 has
      an antithrombotic effect on femoral arterial thrombosis and suggest that an
      increasing action on femoral blood flow of TA-993 is more relevant than its
      antiplatelet action to the antithrombotic effect in this model.

PMID- 9514195
TI  - Molecular defects in the dysmyelinating mutant quaking.
AB  - The quaking [or quakingviable (qk[v])] mutant mouse, which exhibits severe
      dysmyelination of the central nervous system (CNS), has been studied extensively
      over the last 30 years. The genetic defect responsible for the dysmyelinating
      phenotype had remained elusive, however, until the recent cloning of a candidate
      gene, qkI (Ebersole et al.: Nature Genet 12:260-265, 1996). qkI encodes three
      proteins, QKI-5, QKI-6, and QKI-7, which are abundant in myelin-forming cells in
      wild-type mice but whose levels are severely reduced in myelin-forming cells of
      qk(v) mice, consistent with the notion that abnormalities of qkI expression
      underlie the qk(v) phenotype. This review discusses some of the known molecular
      defects in qk(v) in the context of this new information and the potential role of
      QKI proteins in myelinogenesis.

PMID- 9514196
TI  - Central nervous system endothelium in neuroinflammatory, neuroinfectious, and
      neurodegenerative disease.
AB  - Accumulating evidence points toward a significant role for the microvascular
      endothelium in the pathogenesis of several neurologic conditions. This review
      highlights those biochemical, anatomical, and physiological features of the
      endothelium thought to be dysfunctional in these disease states, and elaborates
      on novel treatment modalities that target the endothelium.

PMID- 9514197
TI  - Mechanisms of pHi regulation studied in individual neurons cultured from mouse
      cerebral cortex.
AB  - Maintenance and regulation of intracellular pH (pHi) was studied in single
      cultured mouse neocortical neurons using the fluorescent probe 2',7'-bis-(2
      carboxyethyl)-5,6-carboxyfluorescein (BCECF). Reversal of the Na+ gradient by
      reduction of the extracellular Na+ concentration ([Na+]o) resulted in rapid
      intracellular acidification, inhibited by 5'-(N-ethyl-N-isopropyl)amiloride
      (EIPA), an inhibitor of Na+/H+ exchange. In the presence of EIPA and/or 4',4'
      diisothiocyano-stilbene-2',2'-sulfonic acid (DIDS), an inhibitor of Na+-coupled
      anion exchangers and Na+-HCO3- cotransport, a slow decline of pHi was seen.
      Following intracellular acidification imposed by an NH4Cl prepulse, pHi recovered
      at a rapid rate, which was reduced by reduction of [Na+]o and was virtually
      abolished by EIPA and DIDS in combination. Creating an outward Cl- gradient by
      removal of extracellular Cl- significantly increased the rate of pHi recovery. In
      HCO3(-)-free media, the pHi recovery rate was reduced in control cells and was
      abolished at zero [Na+]o and by EIPA. After intracellular alkalinization imposed
      by an acetate prepulse, pHi recovery was unaffected by DIDS but was significantly
      reduced in the absence of extracellular Cl-, as well as in the presence of Zn2+,
      which is a blocker of proton channels. Together, this points toward a combined
      role of DIDS-insensitive Cl-/HCO3- and passive H+ influx in the recovery of pHi
      after alkalinization.

PMID- 9514198
TI  - Duration and magnitude of nerve growth factor signaling depend on the ratio of
      p75LNTR to TrkA.
AB  - The role of the low affinity neurotrophin receptor p75LNTR in neurotrophin signal
      transduction remains open. Recent reports show that this receptor generates
      intracellular signals independent of Trk activity, and others imply that it
      collaborates with Trk(s) to enhance cellular responses to low neurotrophin
      concentrations. We have used the Cytosensor microphysiometer as a direct marker
      of intracellular metabolic activity to address the physiologic role of p75LNTR in
      nerve growth factor (NGF) signal transduction. NGF treatment of PC12 or TrkA
      transfected Chinese hamster ovary (CHO) cells results in a rapid, transient
      increase in the extracellular acidification rate as measured by the Cytosensor;
      in both cell types, p75LNTR enhances this response. p75LNTR affects both the
      magnitude of and the duration of the extracellular acidification response to NGF.
      Moreover, it is not merely the presence of p75LNTR, but also the ratio of
      p75LNTR:TrkA which determines cellular responsiveness to NGF. In transiently
      transfected CHO cells, a 5:1 ratio of p75LNTR:trkA cDNAs produced the greatest
      change in NGF-induced acid secretion. Pretreatment of PC12 cells with anti
      p75LNTR antibodies decreased the responsiveness to NGF. However, long-term NGF
      exposure to PC12 cells in which p75LNTR expression was decreased to approximately
      10% of wild-type levels showed a longer duration of acid secretion compared to
      wild-type PC12 cells. Together, these data suggest that p75LNTR may play a dual
      role in modulating NGF signal transduction by enhancing and extending cellular
      responses to short-term ligand exposures while attenuating the metabolic response
      to long-term ligand exposures. With regard to potential Trk-independent p75LNTR
      signal transduction mechanisms, we detected no change in extracellular
      acidification response in 75LNTR-transfected CHO cells, PCNA-15 fibroblasts, or
      Schwann cells, all of which express large amounts of p75LNTR and no Trk. Thus,
      p75LNTR cannot produce any signal detected by microphysiometry in the absence of
      TrkA.

PMID- 9514199
TI  - Evidence for non-transferrin-mediated uptake and release of iron and manganese in
      glial cell cultures from hypotransferrinemic mice.
AB  - Transferrin (Tf) is accepted as the iron mobilization protein, but its role in
      transport of other metals is controversial. In this study, we used mixed glial
      cultures from hypotransferrinemic (Hp) mice to determine the dependence of these
      cells on transferrin for iron and manganese delivery and release. Hp mice have a
      splicing defect in the transferrin (Tf) gene, resulting in < 1% of the normal
      plasma levels of Tf. Cellular iron and manganese uptake increases over 24 hr in
      cultures of normal and Hp glial cells in the presence of standard concentrations
      of Tf in the media; although total 59iron uptake in the Hp mouse cultures was 2X
      greater than normal, 54Mn uptake was similar between the two groups. The absence
      of Tf in the media resulted in a significant increase in 59iron uptake in both
      normal and Hp glial but did not affect Mn uptake. Elevated Tf (10X normal) in the
      media reduced both 59iron and 54Mn uptake. Efflux of 59Iron and 54Mn occurred in
      normal and Hp cultures, indicating the existence of a dynamic exchange of metals,
      and that intracellular Tf is not necessary for metal release. However, in the
      absence of Tf in the media, significantly more iron was retained in the cells
      than if Tf were present in both normal and Hp glial cultures. 54Mn release was
      minimally affected by extracellular Tf. The data demonstrate that Tf is not
      required for iron and Mn uptake into glial cells. These data further demonstrate
      a dynamic metal exchange system for glial cells which is not dependent on
      intracellular Tf.

PMID- 9514200
TI  - Subcellular localization of epitope-tagged neurotrophins in neuroendocrine cells.
AB  - A growing body of evidence suggests that neurotrophins (NTs) play a critical role
      in synaptic plasticity and other activity dependent processes in the CNS. Release
      of these growth factors by neurons and neuroendocrine cells was recently shown to
      occur via the regulated secretory pathway, representing a possible mechanism for
      preferentially supplying NTs locally to active synapses. However, the identity
      and characteristics of the intracellular storage compartment for NTs undergoing
      stimulus-coupled secretion remains controversial. As a step towards addressing
      these issues we have investigated the subcellular localization of epitope-tagged
      nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and
      neurotrophin-3 (NT-3) in neuroendocrine cells. Placement of the myc-epitope tag
      at the neurotrophin carboxy terminus did not affect essential properties of the
      NTs such as their ability to induce Trk tyrosine phosphorylation or their sorting
      into the regulated secretory pathway in PC12 and AtT-20 neuroendocrine cells.
      Epitope-tagged NTs colocalize with dense core vesicle (DCV)-markers at the light
      microscopic level in both cell lines investigated. Furthermore, at an EM level
      immunoreactivity (IR) for myc-tagged NGF was found over dense core granules
      (DCGs) in PC12 cells. These data provide evidence that NTs can be stored in DCVs
      in neuronal model cell lines and, potentially, in neurons as well.

PMID- 9514201
TI  - Transplacentally induced neuronal migration disorders: an animal model for the
      study of the epilepsies.
AB  - Recent clinical and laboratory data suggest that there is a link between neuronal
      migration disorders (NMD) and increased seizure threshold. To characterize an
      animal model with features similar to human NMD and to assess seizure
      susceptibility, NMD were induced in the rat at the time of neuroblastic division
      (PG15) and three other gestational ages (PG 13, PG14, PG16) by transplacental
      exposure to methylaxozymethanol (MAM, 25 mg/kg). Offspring pups were monitored
      for spontaneous and electrographic seizures. At postnatal day 14, randomly
      selected rat pups were sacrificed for histological examination. In other MAM
      exposed pups and controls, status epilepticus was induced by intraperitoneal
      administration of kainic acid. On histology, NMD were found in all PG 15 MAM
      exposed rats, in comparison to 63% of PG 13, 70% of PG 14, 80% of PG16.
      Histological features included cortical laminar disorganization, ectopic neurons
      in the subcortical white matter and in cortical layer I, persistent granular
      layer, marginal glioneuronal heterotopia, and discrete areas of neuronal ectopia
      in the CA1 subfield of the hippocampus. Based on the severity of the neuronal
      migration abnormalities, rats were divided into three categories: severe,
      moderate, and mild. Severe and moderate NMD were only found in the PG 15 MAM
      exposed rats. EEG recording in rats with NMD did not disclose spontaneous
      seizures; however, rats with severe NMD had higher slow wave activity compared to
      controls (P < .05). MAM-exposed rats with severe NMD were more susceptible to
      kainic-induced seizures compared to controls (P < .05). In rats with severe NMD,
      kainic acid-induced status epilepticus produced hippocampal damage in the CA3/4
      region. These results demonstrate that MAM-induced NMD have histological and
      electrographic characteristics similar to human NMD. The severity of neuronal
      abnormality depends on the time of transplacental exposure as the most severe NMD
      were found after exposure to MAM at the time of neuroblastic division. The degree
      of NMD positively correlates with seizure susceptibility, since only rats with
      severe NMD have decreased seizure threshold. The occurrence of status epilepticus
      induced hippocampal damage in pups with severe NMD suggests that the severely
      compromised hippocampus is less resistant to seizure-induced injury than the
      normal developing brain.

PMID- 9514202
TI  - Sequential expression of mRNA for proinflammatory cytokines and interleukin-10 in
      the rat peripheral nervous system: comparison between immune-mediated
      demyelination and Wallerian degeneration.
AB  - This study examined the time course of mRNA levels of the proinflammatory
      cytokines interferon-gamma (IFNgamma), interleukin-1beta (IL1beta), interleukin
      12 (IL12; p40 subunit), and the immunosuppressant interleukin-10 (IL10) by
      semiquantitative reverse transcription polymerase chain reaction (RT-PCR) in rats
      with actively induced experimental autoimmune neuritis (EAN) and in distal stumps
      of crushed sciatic nerves undergoing Wallerian degeneration. In EAN IFNgamma- and
      IL1beta-mRNA peaked at the onset and acute phase of clinical disease. IL12p40
      mRNA was upregulated later than IFNgamma-mRNA in the late acute phase from days
      15 to 21. IL10-mRNA appeared concomitantly with the proinflammatory cytokines at
      day 11, but persisted at high levels into the clinical recovery phase. After
      nerve crush both IL1beta- and IL10-mRNA were rapidly upregulated in the distal
      stump at day 1 and slowly declined over the next 2 weeks. Significant levels of
      mRNA for IFNgamma could be found at days 4 and 7, whereas IL12p40-mRNA showed a
      biphasic induction. We provide evidence for a concomitant induction of pro- and
      anti-inflammatory cytokines in EAN. Moreover, the rapid upregulation in Wallerian
      degeneration suggests a more general role of cytokines in the biology of the
      peripheral nerve.

PMID- 9514203
TI  - Apoptotic glial cell death and kinetics in the spinal cord of the myelin
      deficient rat.
AB  - This study examined the glial cell kinetics and death in the thoracic spinal cord
      of normal and myelin-deficient (md) rats between 1 and 21 days of age and
      determined whether the observed glial cell death primarily affected
      oligodendrocytes and had the morphologic and molecular features of apoptosis. In
      the md rat spinal cord there was an increase in cell division and death in a
      pattern that correlated with the onset of myelination. The dying cells were
      identified as oligodendrocytes ultrastructurally as many had the characteristic
      distention of the rough endoplasmic reticulum seen in the md rat glia. Double
      labeling using PLP in situ hybridization and a modified TUNEL method also
      suggested that the dying cells, in both mutant rats and control littermates, were
      oligodendrocytes. These findings were compared with previous studies on the md
      rat optic nerve and those in other PLP mutants.

PMID- 9514204
TI  - Changing responsiveness of developing midbrain dopaminergic neurons for
      extracellular growth factors.
AB  - Numerous purified growth factors as well as yet-unidentified neurotrophic
      activities within mesencephalic glia support the survival of dopaminergic
      neurons. To further characterize the functional role of these multiple growth
      factor influences in dopaminergic cell development, various purified growth
      factors as well as mesencephalic glial-conditioned medium (CM) were screened for
      effects on dopaminergic cell survival and glial numbers in serum-free low density
      cultures of the dissociated embryonic day (E) 15 and E17 rat mesencephalon. In
      E15 mesencephalic cultures, dopaminergic cell survival increased with brain
      derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor
      (GDNF), basic fibroblast growth factor (bFGF), transforming growth factor alpha
      (TGFalpha), insulin-like growth factor-1 (IGF-1), platelet-derived growth factor
      BB (PDGF-BB), and interleukin-6 (IL-6). bFGF, TGFalpha, PDGF, and IL-6 also
      stimulated glial proliferation as demonstrated by autoradiographic labeling for
      3H-thymidine. Moreover, CM derived from the mesencephalic glial cell line Mes42
      completely prevented the death of E15 dopaminergic neurons within the initial
      days of cultivation. In E17 mesencephalic cultures, survival-promoting effects on
      dopaminergic neurons were present with BDNF, GDNF, and bFGF. TGFalpha, IGF-1,
      PDGF-BB, and IL-6 stimulated glial proliferation but did not affect dopaminergic
      cell survival. Similarly, mesencephalic glial-CM completely failed to support the
      survival of E17 dopaminergic neurons. These observations demonstrate that during
      embryonic development, dopaminergic cell survival sequentially depends on
      distinct sets of growth factors. The concomitant loss of sensitivity of
      developing dopaminergic neurons for mesencephalic glial-CM as well as TGFalpha,
      IGF-1, PDGF-BB, and IL-6 further provides evidence that these growth factors
      indirectly affect early dopaminergic neurons through glial-mediated processes and
      suggests a crucial role of glia during the initial stages of neuronal
      development.

PMID- 9514205
TI  - Lipopolysaccharide regulates both serotonin- and thrombin-induced intracellular
      calcium mobilization in rat C6 glioma cells: possible involvement of nitric oxide
      synthase-mediated pathway.
AB  - To investigate the mechanisms by which lipopolysaccharide (LPS) affects Ca2+
      signaling systems, we studied the effects of LPS on the serotonin (5-HT)- or
      thrombin-induced intracellular Ca2+ ([Ca2+]i) increase in rat C6 glioma cells.
      Pretreatment of the cells with 1 microg/ml LPS for 24 hr significantly inhibited
      [Ca2+]i increase induced by 10 microM 5-HT- or 0.5 U/ml thrombin. Its inhibitory
      effects were both dose- and time-dependent. Treatment with 1 mM dibutyryl cGMP
      (dbcGMP) for 30 min also significantly inhibited the 5-HT- and thrombin-induced
      [Ca2+]i increase to approximately 60-70% of control. However, simultaneous
      pretreatment with LPS and dbcGMP did not show any synergistic inhibition. The
      simultaneous pretreatment with LPS and the potent cGMP-dependent protein kinase
      (PKG) inhibitors H-8 and KT5823 for 24 hr significantly antagonized the
      inhibitory effect of LPS. Pretreatment of the cells with 1 microg/ml LPS for 24
      hr significantly enhanced cGMP accumulation, while dexamethasone and NMMA (NOS
      inhibitors) significantly attenuated the LPS-induced enhancement in cGMP
      accumulation. In addition, pretreatment of the cells with 100 nM dexamethasone
      for 24 hr significantly suppressed LPS-induced inducible nitric oxide synthase
      (iNOS; type II NOS, NOS-II) protein expression. These results indicate that LPS
      may inhibit both 5-HT- and thrombin-induced [Ca2+]i increase via iNOS expression
      and PKG activation pathway in rat C6 glioma cells.

PMID- 9514206
TI  - In vitro neuronal and glial production and differentiation of human central
      neurocytoma cells.
AB  - Human central neurocytoma cells were cultured and characterized
      immunophenotypically and electrophysiologically to clarify their developmental
      potential. We conducted systematic in vitro studies utilizing fresh tissues from
      three patients. Initially small homogeneous cell clusters settled down onto the
      bottom of the culture flasks, and, after 2 weeks from plating, mature neuron-like
      cells developed from these clusters and expressed neurofilament proteins (NF:
      specific neuronal markers). On the other hand, approximately 80% of small round
      cell clusters and flat glial-like cells from which these clusters developed were
      positively stained for glial fibrillary acidic protein (GFAP: a specific glial
      marker). Furthermore these neuronal and glial cells showed distinct morphology,
      and dual-label, indirect immunohistochemistry for GFAP and NF-200 kD disclosed
      that the two antigens were not found co-localized in the same cells. In single
      cell clonal analysis, neuronal, glial, and mixed neuronal and glial clones were
      generated. Electrophysiologically, the cells of neuronal morphology possessed
      sodium channels, and also L-type calcium channels in whole-cell voltage clamp.
      The sodium channels were of a characteristic neuronal phenotype which appears in
      neurons. These findings suggest that small round human central neurocytoma cells
      exhibit both neuronal and glial differentiations and have the properties
      reminiscent of precursor cells derived from subventricular matrix; thus, these
      cultured cells may be a potential source for investigations of human CNS neuronal
      and glial development and differentiation.

PMID- 9514207
TI  - Suppressed UDP-galactose: ceramide galactosyltransferase and myelin protein mRNA
      in twitcher mouse brain.
AB  - The developmental changes in expression of steady-state mRNA that encode proteins
      that are important for myelination (myelin basic protein, myelin-associated
      glycoprotein, proteolipid protein, UDP-galactose: ceramide galactosyltransferase)
      and glial fibrillary acidic protein were investigated in the brain of the
      twitcher mouse, a model of human globoid cell leukodystrophy. This disease is
      caused by a mutation in the gene encoding the lysosomal enzyme,
      galactosylceramidase, which catalyzes the degradation of the myelin lipid
      galactosylceramide. Before postnatal day (PND) 20, the levels of myelin protein
      mRNA were similar in twitcher and normal mice. With progression of demyelination
      after PND 25-30, myelin protein mRNA levels gradually decreased. The period of
      maximum expression of the myelin protein genes in twitcher mice was, however,
      similar to that of normal control mice. mRNA levels for the gene that encodes the
      enzyme UDP-galactose:ceramide galactosyltransferase which is responsible for
      catalyzing the final step in galactosylceramide synthesis, was exceptionally down
      regulated from the early stages of the disease. The increase of glial fibrillary
      acidic protein (GFAP) mRNA levels preceded morphological evidence of
      demyelination.

PMID- 9514208
TI  - Inhibition of dopamine and choline acetyltransferase concentrations in rat CNS
      neurons by rat alpha 1- and alpha 2-macroglobulins.
AB  - Previous studies have implicated human alpha-2-macroglobulin (alpha2M) as a
      potential regulator of neuronal development and function. Rat alpha-1
      macroglobulin (alpha1M) and acute-phase alpha-2-macroglobulin (alpha2M) are
      murine homologues of human alpha2M. In this report, we tested the effect of
      intracranially infused serotonin-activated rat alpha1M (5HT-alpha1M) on the
      concentration of dopamine (DA) in the corpus striatum in vivo and the effect of
      5HT-activated rat alpha1M and alpha2M on the choline acetyltransferase (ChAT)
      activity upon embryonic basal forebrain neurons in culture. The results show that
      direct infusion of 0.65 nmole rat 5HT-alpha1M into the adult rat corpus striatum
      produced a consistent attenuation upon striatal DA concentrations. This decrease
      was particularly prominent at 5-7 days post-infusion. In addition, rat 5HT
      alpha1M and rat 5HT-alpha2M, like human 5HT-alpha2M, all significantly inhibited
      ChAT activity of embryonic rat cerebral cortex neurons. Although normal human
      alpha2M and rat alpha2M were either marginally or insignificantly inhibitory in
      this preparation, normal rat alpha1M dose-dependently inhibited ChAT activity.
      These results demonstrate that monoamine-activated alpha-macroglobulins from rat
      depress dopaminergic and cholinergic neurotransmitter systems in the CNS, and
      this suggests a potential regulatory role of these alpha-macroglobulins in
      neurotransmitter metabolism.

PMID- 9514209
TI  - Collagen cross-links in mineralizing tissues: a review of their chemistry,
      function, and clinical relevance.
AB  - Bone collagen cross-links are now widely used to assess bone resorption levels in
      many metabolic bone diseases. The post-translational modifications of bone and
      other mineralizing collagens are significantly different from those of other type
      I collagen matrices, a fact that has been exploited during recent advances in the
      development of biochemical markers of bone resorption. The enzymatic collagen
      cross-linking mechanism is based upon aldehyde formation from specific
      telopeptide lysine or hydroxylysine residues. The immature ketoimine cross-links
      in bone form via the condensation of a telopeptide aldehyde with a helical lysine
      or hydroxylysine. Subsequent maturation to the pyridinoline and pyrrole cross
      links occur by further reaction of the ketoimines with telopeptide aldehydes. In
      mineralizing tissues, a relatively low level of lysyl hydroxylation results in
      low levels of hydroxylysyl pyridinoline, and the occurrence of the largely bone
      specific lysyl pyridinoline and pyrrolic cross-links. The collagen post
      translational modifications appear to play an integral role in matrix
      mineralization. The matrix of the turkey tendon only mineralizes after a
      remodeling of the collagen and the subsequent formation of a modified matrix more
      typical of bone than tendon. Further, disturbances in the post-translational
      modification of collagen can also affect the mineralization density and crystal
      structure of the tissue. In addition to their use as a convenient measure of
      matrix degradation, collagen cross-links are of significant importance for the
      biomechanical integrity of bone. Recent studies of osteoporotic bone, for
      example, have demonstrated that subtle perturbations in the pattern of lysine
      hydroxylation result in changes in the cross-link profile. These alterations,
      specifically changes in the level of the pyrrolic cross-link, also correlate with
      the strength of the bone. Further research into the biochemistry of bone collagen
      cross-links may expand current understanding and their clinical application in
      metabolic bone disease. This review also demonstrates the potential for further
      study into this area to provide more subtle information into the mechanisms and
      etiology of disease and aging of mineralizing tissues.

PMID- 9514210
TI  - Localization of parathyroid hormone-related protein in osteoclasts by in situ
      hybridization and immunohistochemistry.
AB  - Using immunohistology with two specific antisera raised against N-terminal
      parathyroid hormone-related protein (PTHrP) and in situ hybridization (riboprobe
      to common coding exon), evidence is provided for the expression of PTHrP by
      mouse, rabbit, and human osteoclasts derived from several in vitro and in vivo
      sources. In cocultures of mouse bone marrow and calvarial cells treated with 1,25
      dihydroxyvitamin D3, the generated osteoclasts expressed both PTHrP messenger RNA
      (mRNA) and protein. In addition, PTHrP was detected in the majority of actively
      resorbing osteoclasts in sections of newborn and adult mouse long bones. Using an
      in vivo intramembranous bone formation model in rabbits, expression of PTHrP mRNA
      and protein was demonstrated in osteoclasts at active bone resorption sites as
      well as in actively synthesizing osteoblasts and bone lining cells. Localization
      of PTHrP was also demonstrated in osteoclast-like cells of human giant cell
      tumors from bone. In some of these tumors, a small proportion of the
      multinucleated cells expressed tartrate resistant acid phosphatase (TRAP), but
      not PTHrP mRNA or protein. Finally, both mRNA and protein for PTHrP were
      expressed in osteoclasts in sections of bone or joints from patients with Paget's
      disease, rheumatoid arthritis, and osteoarthritis. These observations raise the
      possibility that PTHrP might participate in osteoclast function.

PMID- 9514211
TI  - P2Y2 receptors are expressed by human osteoclasts of giant cell tumor but do not
      mediate ATP-induced bone resorption.
AB  - Extracellular nucleotides acting through P2 receptors elicit a range of responses
      in many cell types. Previously, we have cloned the G-protein coupled P2Y2
      receptor from a human osteoclastoma complementary deoxyribonucleic acid (cDNA)
      library and demonstrated its expression by reverse transcription linked (RT)-PCR
      and Southern analysis in a number of skeletal tissues, including a purified
      population of giant cells. In this study we have localized the expression of P2Y2
      receptor transcripts to osteoclasts of giant cell tumor of bone by in situ
      hybridization. In osteoblasts and other cell types, the P2Y2 receptor is coupled
      to Ins(1,4,5)P3-mediated Ca2+ release from intracellular stores. In this study,
      the P2Y2 receptor agonists adenosine triphosphate (ATP) and uridine triphosphate
      (UTP) did not increase cytosolic free calcium concentration ([Ca2+]i) in giant
      cells isolated from osteoclastoma, while the G-protein coupled calcium sensing
      receptor agonist, Ni2+, elevated [Ca2+]i in the same cells. These data indicate
      that P2Y2 receptor transcripts expressed by giant cells are not presented at the
      surface of cells as functional receptors, or alternatively, functional receptors
      are coupled to an effector other than [Ca2+]i. ATPgammaS (10 micromol/L), but not
      UTP (10 micromol/L), significantly stimulated resorption by an enriched giant
      cell population. These results indicate that ATP-induced effects on resorption,
      following direct osteoclastic activation, are mediated by a P2 receptor other
      than the P2Y2 subtype. Nucleotides, released locally in the bone microenvironment
      in response to acute trauma or transient physical stress, will interact with a
      complement of P2 receptors expressed by both osteoclasts and osteoblasts to
      influence the remodeling process.

PMID- 9514212
TI  - Estrogen enhances differentiation of osteoblasts in mouse bone marrow culture.
AB  - The effects of estrogen on bone are possibly mediated by several cell types. In
      the present study, the effect of 17beta-estradiol (E2) on osteoblast-like cells
      was investigated by using mouse bone marrow cultures. Bone marrow cells were
      harvested from the shafts of femurs of 10-week-old NMRI mice and cultured. On day
      6, confluent primary cultures were trypsinized and subcultured. Under the
      conditions used (Keila, S., Pitaru, S., Grosskopf, A., and Wernreb, M. Bone
      marrow from mechanically unloaded rat bones expresses reduced osteogenic capacity
      in vitro. J Bone Miner Res 9:321-327; 1994), the bone marrow cultures showed
      differentiation towards the osteoblastic phenotype. This was demonstrated by the
      appearance of osteoblastic markers such as alpha1(I) collagen (COL1), alkaline
      phosphatase (ALP), osteocalcin (OCN), osteopontin (OP), and transforming growth
      factor-beta1 (TGFbeta1), which were detected by using reverse transcriptase
      polymerase chain reaction (RT-PCR). Bone nodule formation, including deposition
      of collagen fibers and matrix mineralization, was also studied at several time
      points of the 3-week culture period. The effect of E2 on the appearance of
      osteoblastic markers was studied by incubating cultures in the presence or
      absence of the hormone. The messenger ribonucleic acid (mRNA) for the estrogen
      receptor (ER) was found to be expressed at all time points as demonstrated by RT
      PCR. When grown with E2, the rate of cell proliferation was increased in the
      early phase of cultures, but not after day 6. The addition of E2 in subcultures
      resulted in an increase of levels of mRNA for COL1, ALP, OCN, OP, and TGF-beta1.
      ALP activity was also increased. Bone nodule formation, as well as calcium
      contents, were significantly increased in the cultures grown in the presence of
      E2. All E2 concentrations used (0.01-10 nmol/L) were effective but the maximum
      response was obtained with 0.1 nmol/L E2. Addition of the antiestrogen ICI
      182,780 abolished the E2-induced stimulation of proliferation and later an
      increase in ALP activity. Addition of ICI 182,780 without the hormone did not
      cause any changes when compared to control cultures. In conclusion, our results
      demonstrate that E2 stimulates sequential differentiation of osteoblasts and
      increases deposition and mineralization of matrix in mouse bone marrow cultures
      in an estrogen receptor-dependent manner.

PMID- 9514213
TI  - Alkaline phosphatase levels and osteoprogenitor cell numbers suggest bone
      formation may contribute to peak bone density differences between two inbred
      strains of mice.
AB  - Previous studies have shown that C3H/HeJ (C3H) mice have higher peak bone density
      than C57BL/6J (B6) mice, at least in part because of differences in rates of bone
      resorption. The current studies were intended to examine the alternative,
      additional hypothesis that the greater bone density in C3H mice might also be a
      consequence of increased bone formation. To that end, we measured two
      presumptive, indirect indices of bone formation and osteoblast number in these
      inbred strains of mice: alkaline phosphatase (ALP) activity in serum, bones, and
      bone cells; and the number of ALP-positive colony-forming units (CFU) in bone
      marrow stromal cell cultures. We found that C3H mice had higher serum levels of
      ALP activity than B6 mice at 6 (118 vs. 100 U/L, p < 0.03) and 32 weeks of age
      (22.2 vs. 17.2 U/L, p < 0.001). Tibiae from C3H mice also contained higher levels
      of ALP activity than tibiae from B6 mice at 6 (417 vs. 254 mU/mg protein, p <
      0.02) and 14 weeks of age (132 vs. 79 mU/mg protein, p < 0.001), as did monolayer
      cultures of bone-derived cells from explants of 7.5-week-old C3H calvariae and
      femora (8.2 times more, p < 0.02, and 4.6 times more, p < 0.001, respectively).
      Monolayer cell cultures prepared by collagenase digestion of calvariae from
      newborn and 6-week-old mice also showed similar strain-dependent differences in
      ALP-specific activity (p < 0.001 for each). Our studies also showed more ALP
      positive CFU in bone marrow stromal cell cultures from 8-week-old C3H mice,
      compared with B6 mice (72.3 vs. 26.1 ALP-positive CFU/culture dish, p < 0.001). A
      similar result was seen for ALP-positive CFU production at 6 and 14 weeks of age,
      and the difference was greatest for the CFU that contained the greatest numbers
      of ALP-positive cells. Because skeletal ALP activity is a product of osteoblasts
      and has been shown to correlate with rates of bone formation, and because the
      number of ALP-positive CFU is believed to reflect the number of osteoprogenitor
      cells, the current data are consistent with the general hypothesis that bone
      formation may be greater in C3H than B6 mice because of a difference in
      osteoblast number. Our data further suggest that peak bone density may be greater
      in C3H mice than B6 mice due to a combination of decreased bone resorption and
      increased bone formation.

PMID- 9514214
TI  - Early effects of short-term parathyroid hormone administration on bone mass,
      mineral content, and strength in female rats.
AB  - The present study was designed to examine the metabolic changes and early effects
      of short-term parathyroid hormone (PTH) treatment on bone mass, mineral content,
      and strength. Forty-eight 10-week-old intact female rats were randomized into six
      groups. The three PTH-treated groups were subcutaneously given PTH 50 microg/kg
      body weight daily for 5 (PTH5), 10 (PTH10), or 15 (PTH15) days. The three
      respective time control groups (C5, C10, and C15) were injected with saline
      solution. In serum, total calcium, alkaline phosphatase, and insulin-like growth
      factor-I (IGF-I) were analyzed. Bone mass was estimated with wet and dry weights
      of the femora and hydroxyproline content of the tibiae. Ash weight and calcium,
      magnesium, and phosphorus contents (determined by AAS) were used to measure
      femoral mineral content. Bone mineral density (BMD) of the femora was measured
      using dual-energy X-ray absorptiometry (DXA) and the biomechanical properties of
      the femoral neck were tested. After 5 days of PTH treatment, some trends of the
      anabolic actions of PTH could be observed, but there was no significant effect on
      relevant parameters of bone formation. After 10 days, bone mass, mineral content
      (assessed by ash weight), and BMD of the PTH-treated rats were significantly
      increased compared with those of controls. The relative femoral magnesium content
      of the PTH-treated animals was significantly higher than that of controls. After
      15 days, the length of the femora, bone mass, mineral content, BMD, and the width
      of the femoral neck were increased, and its biomechanical properties were
      significantly improved in PTH-treated rats compared with the respective time
      control group. PTH treatment significantly increased circulating alkaline
      phosphatase and decreased systemic IGF-I concentrations throughout the study. In
      conclusion, intermittent PTH administration to still growing female rats is
      anabolic in bone with significant effects already taking place after 10 days of
      treatment. The effects of PTH consisted of: (1) an increase in bone mass and
      mineral content with a transient augmentation of relative magnesium content; and
      (2) improved width and mechanical properties of the femoral neck after 15 days of
      treatment. These effects are accompanied by an increase in longitudinal bone
      growth. They are unlikely related to any changes in systemic IGF-I
      concentrations.

PMID- 9514215
TI  - Effects of calcium depletion and repletion on serum insulin-like growth factor I
      and binding protein levels in weanling rats.
AB  - Previous studies in a weanling rat model indicated that dietary calcium depletion
      not only stimulated osteoclastic resorption but also inhibited bone formation.
      The present study sought to test whether the depletion-associated inhibition of
      bone formation is related to a reduction in serum insulin-like growth factor-I
      (IGF-I) and/or an increase in its binding proteins (IGFBPs). Twenty male weanling
      rats were divided into two weight-matched groups. The study group was subjected
      to a semisynthetic diet deficient in calcium (0.02% calcium) for 28 days, while
      the control group was pair-weighed on the same diet but containing 0.62% calcium.
      After the depletion phase, all rats were fed the same calcium-containing diet for
      an additional 14 days. Serum samples were obtained from each animal on a weekly
      basis and assayed for IGF-I and IGFBPs. During depletion, there was no
      statistically significant difference in serum IGF-I level between the study group
      and the control group. In contrast, the study group showed a statistically
      significant increase in several serum IGFBPs with apparent molecular size of 30
      38 kD (IGFBP-3), 26-28 kD (IGFBP-1, -2, -5, and/or -6), and 24-25 kD (IGFBP-4),
      respectively, compared to the control group. There was no difference in
      nutritional intakes between the two groups of rats during depletion. During
      repletion, there was also no significant difference in serum IGF-I level between
      the control and study group. However, during the first 7 days of repletion, serum
      IGFBP-3 and the 26-28 kD IGFBP of the study group was significantly less than
      those of the control group, which then returned to the control level after 2
      weeks of repletion. In summary: (1) calcium depletion in weanling rats increased
      several serum IGFBPs without an effect on IGF-I; and (2) calcium repletion
      induced an acute reduction in serum IGFBP-3. In conclusion, these findings
      represent the first evidence that the depletion-related inhibition of bone
      formation in the rat may be associated with an increase in several serum IGFBPs,
      which may act to inhibit the osteogenic actions of IGFs.

PMID- 9514216
TI  - Effect of estrogen suppression on the mineralization density of iliac crest
      biopsies in young women as assessed by backscattered electron imaging.
AB  - The effects of estrogen suppression on bone mineralization in young women were
      studied by quantitative backscattered electron (BSE) imaging of transiliac
      biopsies taken before and after treatment for endometriosis. Treatment (6 months)
      was with analogs of gonadotrophin releasing hormone (GnRH) given either alone
      (six paired biopsies), which resulted in a marked reduction in the levels of
      circulating estrogen, or in conjunction with tibolone, a synthetic steroid with
      estrogenic, progestrogenic, and androgenic properties (four paired biopsies).
      Estrogen withdrawal increased (p < 0.01) and concomitant tibolone treatment
      decreased (p < 0.05) the overall mean bone density. Estrogen withdrawal increased
      the fraction of bone with a high mineralization density [pretreatment: 0.236+/
      0.007; GnRH: 0.279+/-0.009, mean +/- standard error of the mean (SEM); p < 0.01].
      The concomitant addition of tibolone reversed these effects and increased the
      proportion of bone with a low mineralization density (pretreatment: 0.198 +/-
      0.005; tibolone: 0.230 +/-0.008, p < 0.01). Using previously published data, the
      mean bone density was inversely correlated with mean wall thickness in cancellous
      bone (p = 0.030) and with the percentage of active osteons (p = 0.023) in
      cortical bone. Although treatment had similar effects on the mean bone
      mineralization density of cortical and cancellous bone, there were different
      distributions of mineralization between the two sites, with cancellous bone
      having more skewed and kurtotic distributions both before and after estrogen
      withdrawal. This study indicates that a short-term estrogen suppression results
      in the accumulation of bone with a higher mineralization density. As bone with a
      high mineral content has a decreased impact resistance, this might increase
      fracture risk. Understanding the cellular and biochemical mechanisms responsible
      for the local distribution of bone mineral when estrogen is withdrawn may allow
      the development of new strategies for maintaining bone quality after menopause.

PMID- 9514217
TI  - Culture of stromal cells derived from medullary cavity of human long bone in the
      presence of 1,25-dihydroxyvitamin D3, recombinant human bone morphogenetic
      protein-2, or ipriflavone.
AB  - We previously showed that stromal cells derived from bone marrow specimens formed
      at the fracture site of human long bone differentiated during culture to
      polygonal cells and spindle cells, and polygonal cells, but not spindle cells,
      produced calcified matrix. To clarify the origin of polygonal and/or spindle
      cells, and factors necessary for differentiation of marrow stromal cells to
      osteogenic cells, we cultured stromal cells derived from the normal (unfractured)
      medullary cavity (SCN) as well as stromal cells from the medullary cavity distant
      from the fracture site (SCF). After 3 weeks of primary culture and 2 days of
      secondary culture, the cells were cultured in medium containing 1,25
      dihydroxyvitamin D3 (VD), recombinant human bone morphogenetic protein-2 (BMP),
      or ipriflavone (IF) for 3 weeks. For biochemical analysis, cells reaching
      confluence after 3 weeks of secondary culture were cultured with one of the
      factors for 3 days. Some of SCF cultured with VD or IF were transformed to
      polygonal cells, and showed high alkaline phosphatase (ALPase) activity and high
      osteocalcin and insoluble calcium production. Cloned polygonal cells from the SCF
      formed nodules and aggregates consisting of calcium. Other SCF cultured with VD
      or IF and SCF cultured with BMP were spindle shaped. Some spindle-shaped cells
      from SCF cultured with BMP or IF revealed high ALPase activity and high
      osteocalcin production, comparable with the spindle cells from the fracture site.
      However, spindle-shaped cells from SCF cultured with VD and other spindle-shaped
      cells from SCF cultured with BMP or IF showed low ALPase activity and low
      osteocalcin production. The results show that SCF probably contain at least three
      subpopulations: (a) cells that differentiate to polygonal cells by the influence
      of VD or IF; (b) cells that differentiate to the spindle cells by the influence
      of BMP or IF; and (c) cells that are not transformed by the influence of VD, BMP,
      or IF.

PMID- 9514218
TI  - Bone disease in African children with slipped capital femoral epiphysis:
      histomorphometry of iliac crest biopsies.
AB  - African teenagers with slipped capital femoral epiphysis (SCFE) not infrequently
      also have genu valgum (knock-knee). Because we had previously demonstrated
      metabolic bone disease attributable to dietary calcium deficiency in black
      teenagers with genu valgum, we examined 29 black teenagers (15 male, 14 female)
      with SCFE for metabolic bone disease. Each patient had an iliac crest bone biopsy
      taken (after double tetracycline labeling) for routine histomorphometry, and
      blood and urine samples for bone biochemistry. Spinal bone mineral density was
      measured in 13 patients. Compared to reported data, we found our patients to be
      sexually more immature, older, at least as obese, and to have more severe and
      more frequently bilateral hip disease. Eighty percent of the children took dairy
      products only once or twice a week or less frequently, and 37.9% had genu valgum.
      Compared with race- and age-matched South Africans, bone biopsies in our patients
      showed lower bone volume (BV/TV, p = 0.0003), wall thickness (p = 0.0002), and
      trabecular thickness (Tb.Th, p = 0.0002), and a tendency to greater trabecular
      spacing (Tb.Sp, p = 0.053). Lower osteoid volume (OV/BV, p = 0.0001), osteoid
      surface (OS/BS, p = 0.0001), osteoid thickness (O.Th, p = 0.0002), double labeled
      surface (dLS/BS, p = 0.029), and bone formation rate (BFR/BS, p = 0.037)
      suggested poorer bone forming capacity in our patients. No evidence of
      hyperparathyroid bone disease or osteomalacia was found. BV/TV was below the
      reference range (14.2%) in 65.5% of cases; these patients had lower values for
      Tb.Th (p = 0.037) and Tb.N (p = 0.0003), greater Tb.Sp (p = 0.0002), a tendency
      to lower adjusted apposition rate (Aj.AR, p = 0.057), and had had less frequent
      intake of dairy products than those with normal BV/TV (p = 0.024). Furthermore,
      months since menarche correlated with histomorphometric variables BV/TV (r =
      0.667, p = 0.009), Tb.Th (r = 0.745, p = 0.002), Tb.Sp (r = -0.549, p = 0.042),
      O.Th (r = 0.784, p = 0.0009), and Aj.AR (r = 0.549, p = 0.042). The correlation
      between Tb.Th and spinal bone mineral content (r = 0.656, p = 0.015) suggests
      that the reduced trabecular thickness reflected a generalized bone condition. A
      greater than normal proportion of patients had spinal bone mineral density values
      below -1 standard deviation (SD) of the mean (osteopenia) (p = 0.001). Patients
      tested for parathyroid hormone and 25-hydroxyvitamin D levels were found to have
      normal values. Parathyroid hormone correlated with Aj.AR (r = 0.661, p = 0.038)
      and serum phosphorus (r = -0.764, p = 0.010). We conclude that sexual immaturity
      and possibly past dietary calcium deficiency contributed to osteopenia, and that
      this, together with obesity, led to the development of more severe and more
      frequently bilateral SCFE in our patients than in reported series of black and
      white children.

PMID- 9514219
TI  - Mechanisms of bone loss after cardiac transplantation.
AB  - To determine the mechanism of bone loss after cardiac transplantation (CTX), we
      studied 50 men 0.5-47 months after CTX (ages 18-64 years) who received
      prednisolone and cyclosporin to prevent rejection, and 40 healthy men as controls
      (ages 20-70 years). We measured bone mineral density (BMD) using dual-energy X
      ray absorptiometry (DXA), bone resorption using urinary cross-linked N-terminal
      telopepides of type I collagen (NTx), and bone formation using osteocalcin (BGP)
      and bone alkaline phosphatase (BAP). The results from the controls were used to
      calculate z scores. BMD was significantly decreased at the lumbar spine, femoral
      neck, and total body, and bone turnover was significantly increased as assessed
      by NTx/creatinine, BGP, and BAP as compared with controls (p < 0.01 for all
      measurements). To evaluate the cause of the increased bone turnover we measured
      serum parathyroid hormone (PTH) by IRMA, and this was also elevated (p < 0.001).
      There was a significant correlation between serum PTH and BGP (r = 0.58, p <
      0.01). To evaluate the cause of the increase in PTH, we measured serum calcium
      and it was decreased (p < 0.001), serum phosphorus was increased (p < 0.001),
      serum creatinine was increased (p < 0.001), and serum 1,25-dihydroxyvitamin D3
      [1,25(OH)2D, RIA] was decreased (p = 0.03). Serum PTH correlated weakly with
      serum calcium (r = -0.41, p < 0.003) and with serum creatinine (r = 0.35, p =
      0.01). There was a weak, but significant, correlation between serum creatinine
      and 1,25(OH)2D3 (r = 0.33, p = 0.03). Serum levels of testosterone and
      dehydroapiandrosterone sulfate were decreased after CTX but did not correlate
      with any other parameters. There was a weak negative correlation between
      prednisolone daily dose and serum BGP level (r = 0.29, p = 0.06) in those
      patients whose prednisolone current dose was >7.5 mg/day. We conclude that: (1)
      the low BMD found after CTX is associated with increased bone turnover which
      results, in turn, from renal impairment; (2) prednisolone is involved in rapid
      bone loss, whereas mild secondary hyperparathyroidism may be a major contributor
      to disorder of bone remodeling after this rapid loss; and (3) decreased androgen
      levels may not be a major factor resulting in bone loss in men after CTX.

PMID- 9514220
TI  - Drinking water fluoridation: bone mineral density and hip fracture incidence.
AB  - The role of drinking water fluoride content for prevention of osteoporosis
      remains controversial. Therefore, we analyzed the influence of drinking water
      fluoridation on the incidence of osteoporotic hip fractures and bone mineral
      density (BMD) in two different communities in eastern Germany: in Chemnitz,
      drinking water was fluoridated (1 mg/L) over a period of 30 years; in Halle, the
      water was not fluoridated. BMD was measured in healthy hospital employees aged 20
      60 years (Halle: 214 women, 98 men; Chemnitz: 201 women, 43 men, respectively)
      using dual-energy X-ray absorptiometry. Hip fractures in patients > or = 35 years
      admitted to the local hospitals in the years 1987-1989 were collected from the
      clinic registers. There was no difference in age, anthropometric, hormonal, or
      lifestyle variables between the two groups. Mean fluoride exposure in Chemnitz
      was 25.2 +/- 7.3 years. No correlation was found between fluoride exposure and
      age-adjusted BMD. We found no significant difference in spinal or femoral BMD
      between subjects living in Halle and Chemnitz [lumbar spine: 0.997 +/- 0.129
      (g/cm2) vs. 1.045 + 0.171 (g/cm2), p = 0.08, for men; 1.055 +/- 0.112 (g/cm2) vs.
      1.046 +/- 0.117 (g/cm2), p = 0.47, for women]. The fracture incidence showed an
      exponential increase with aging in men and women with an incidence about 3.5
      times higher for women. In Chemnitz, we calculated an age-adjusted annual
      incidence of 142.2 per 100,000 for women and 72.5 per 100,000 for men,
      respectively. In Halle, the incidences were 178.5 per 100,000 for women and 89.2
      per 100,000 for men. There was a lower hip fracture incidence after the age of 85
      in women in Chemnitz (1391 per 100,000 in Chemnitz vs. 1957 per 100,000) in
      Halle, p = 0.006). Using the age-adjusted incidences, significantly fewer hip
      fractures occurred in Chemnitz in both men and women. In conclusion, our study
      suggests that optimal drinking water fluoridation (1 mg/L), which is advocated
      for prevention of dental caries, does not influence peak bone density but may
      reduce the incidence of osteoporotic hip fractures in the very old.

PMID- 9514221
TI  - Relationship between bone density and osteoarthritis in a skeletal population
      from London.
AB  - To determine whether bone density was related to the presence of osteoarthritis
      in past populations, bone density was determined directly on bone slices taken
      from the fourth lumbar vertebra of a series of skeletons from a cemetery in
      London used from the middle 18th to the early 19th centuries. Eighty male and 57
      female skeletons were studied and standard anthropological methods were used to
      determine age and gender. Osteoarthritis was diagnosed by the presence of
      eburnation on joint surfaces. The mean bone density in the males was 0.351 (+/
      0.071) g/cm2, and in the females 0.332 (+/-0.091); this difference was
      statistically significant (p = 0.045). There was a significant, negative
      relationship with bone density and age in females (p = 0.0023), but not males (p
      = 0.073). Forty-seven of the males and 30 of the females had osteoarthritis, the
      most commonly affected joints being the facet joints of the spine and the hands.
      For the males there was no significant difference in bone density in those with
      or without osteoarthritis, but in females the bone density was significantly
      lower (p = 0.021) in those with osteoarthritis than in those without. The reasons
      why this result differs from modern populations in which patients with
      osteoarthritis tend to have higher bone density are discussed, and it is
      suggested that the most plausible explanation may relate to differences in
      nutritional status between past and modern populations.

PMID- 9514222
TI  - Rapid skeletal turnover and hypercalcemia associated with markedly elevated
      interleukin-6 levels in a young black man.
AB  - A 24-year-old black man presented with diffuse musculoskeletal pain and shotty
      lymphadenopathy. Laboratory studies revealed hypercalcemia and hyperphosphatemia,
      very high serum alkaline phosphatase activity, diffuse but intense uptake of
      radionuclide on a bone scan, urinary N-telopeptide excretion 30 times the upper
      limit of normal, and serum interleukin-6 100 times the upper limit of normal. An
      extensive workup for etiologies of the disorder was negative. A bone biopsy
      revealed intense osteoclastic resorption coupled with rapid bone formation and/or
      remodeling. This case appears to represent a new entity. Treatment with
      bisphosphonates produced symptomatic and biochemical improvement.

PMID- 9514223
TI  - Total body mineral mass versus total fat mass.

PMID- 9514224
TI  - The impact of multiple organ dysfunction on mortality following ruptured
      abdominal aortic aneurysm repair.
AB  - The in-hospital mortality for a patient with a ruptured abdominal aortic aneurysm
      (RAAA) ranges from 30% to 70% and remains unchanged despite aggressive surgical,
      anesthetic, and intensive-care management. The purpose of this investigation is
      to determine the relationship between the development of organ dysfunction and
      mortality in ruptured AAA patients. Eighty-eight consecutive patients admitted to
      the Toronto Hospital for repair of RAAAs were studied. APACHE II and multiple
      organ dysfunction (MOD) scores were calculated for all patients. The MOD scoring
      system measures daily alterations in the function of six key organs, with
      increased dysfunction indicated by an increasing score. The overall 30-day
      mortality rate was 40%; 10% of patient deaths occurred intraoperatively. ICU
      mortality was bimodal; 11.5% deaths occurred within the first 48 hours compared
      to 18.2% after 48 hours (late deaths). The APACHE II score was significantly
      higher in those who died within 48 hours of ICU admission (28.5 +/- 6.36)
      compared to both those who died late (17.2 +/- 5.7, p < 0.0001) and survivors
      (11.2 +/- 4.2, p < 0.0001). The survivors' daily mean MOD scores did not increase
      significantly, while the MOD scores for late deaths increased progressively (p <
      0.01). The renal and hepatic dysfunction components of the MOD score were
      significantly lower in the survivors compared to late deaths (p < 0.001), however
      the respiratory MOD score did not differ between the groups (p > 0.05). The
      change in MOD (delta MOD) score over the intensive care stay was significantly
      greater in late deaths compared to survivors (p < 0.01). The rates of infection
      were similar in both groups and were not responsible for mortality. We conclude
      that mortality is better predicted following RAAA by the development of renal and
      hepatic dysfunction rather than by initial physiologic derangement measured by
      the APACHE II score.

PMID- 9514225
TI  - Prevalence of abdominal aortic aneurysms in patients undergoing coronary artery
      bypass.
AB  - Although several studies describe the prevalence of coronary artery disease in
      patients with abdominal aortic aneurysms (AAA), the opposite relationship is
      virtually unexplored. It is the purpose of this study to determine the prevalence
      of AAA in patients with severe coronary artery disease undergoing bypass grafting
      (CABG). Patients scheduled for elective CABG underwent aortic ultrasound (US)
      preoperatively. A control group of patients without cardiovascular disease also
      underwent US. An AAA was defined as a maximal diameter > or =3.0 cm. US was
      performed on 192 CABG patients and 140 controls. The overall prevalence
      (previously repaired AAA and new cases) of AAA in CABG patients was 18.2%. The
      prevalence of new cases of AAA was 13.0% compared to 1.4% in controls (p =
      0.0001). Ten patients had an AAA greater than 5.0 cm in size (5.2%). Logistic
      regression identified age > or =65 years and smoking as significant risk factors
      for AAA in the CABG population. The higher prevalence of AAA in CABG patients was
      confirmed by a case-control analysis of 73 age-matched patients. This study
      provides the first convincing evidence that the prevalence of AAA is higher in
      patients undergoing CABG than in the control population in Vermont. Consideration
      should be given to screening patients for AAA who are undergoing CABG,
      particularly older, smoking males.

PMID- 9514226
TI  - Outcomes after abdominal aortic aneurysm repair in those > or =80 years of age:
      recent Veterans Affairs experience.
AB  - During fiscal years 91-95, 6260 patients underwent 6269 abdominal aortic aneurysm
      (AAA) repairs in Veterans Affairs Medical Centers. Those > or =80 years old
      comprised 3.7% (n = 231) of the patients. A total of 5833 patients underwent
      repair of nonruptured AAA: mortality was 4.1% (228/5627) in those <80 and 8.25%
      (17/206) in those > or =80 years old (p < 0.009). Logistic regression analysis
      indicated age > or =80 was independently associated with higher mortality (odds
      ratio 1.834:1, 95% bounds 1.117-3.012). Octogenarian status (defined as > or =80
      years of age), however, had a less important association with in-hospital death
      than did surgical complications of the heart or genitourinary tract,
      postoperative hemorrhage, septicemia, respiratory insufficiency, myocardial
      infarction (MI), acute renal failure, surgical complications of the central
      nervous system (CNS), aneurysm rupture, postoperative shock, or disseminated
      intravascular coagulation (DIC), in ascending order of importance. Only 5.9% (n =
      25) of the 427 patients undergoing repair of ruptured AAA were > or =80 years
      old. In those > or =80 undergoing repair of ruptured aneurysms, mortality was 48%
      which did not differ from the 45% mortality in those <80 (NS). The likelihood
      that one would be operated for rupture was statistically greater (1.66:1) for
      those > or =80 years (p < 0.025). Length of stay (LOS) for those > or =80
      undergoing AAA repair was longer being 22.3 +/- 14.8 days versus 18.3 +/- 13.2
      days for younger patients (p < 0.001). Mortality and LOS after AAA repair were
      statistically greater for those > or =80 years of age. Severity of illness,
      however, was also greater for octogenarians. Patient Management Category (PMC)
      software defined illness severity was 4.06 +/- 1.22 in octogenarians versus 3.84
      +/- 1.13 for those younger (p < 0.005). Though age > or =80 was independently
      associated with increased mortality, selected elderly patients could benefit from
      AAA repair.

PMID- 9514227
TI  - Thoracoabdominal aortic aneurysm repair in patients with single kidney.
AB  - Data were analyzed from 581 consecutive cases of thoracoabdominal aortic aneurysm
      (TAAA) repairs. Preoperatively, 32 patients (6%) had only one functioning kidney
      (single-kidney group), and 549 patients (94%) had tow functioning kidneys
      (reference group). The patients' mean age was higher in the reference group (64.9
      years, range: 21-85) than in the single-kidney group (63.2 years, range: 38-79);
      p < 0.05. However, there was a significantly higher incidence of hypertension
      (97% versus 78%), coronary artery disease (50% versus 34%), and renal artery
      stenosis ipsilateral to functioning kidneys (88% versus 26%) in the single-kidney
      group than in the reference group; p < 0.05. Preoperatively, renal insufficiency
      (serum creatinine > or = 2.5 mg/dl or patients on dialysis) was present in four
      patients (13%) in the single-kidney group and in 21 patients (4%) in the
      reference group; p < 0.05. In the former group, the unilateral loss of kidney
      function was secondary to atrophy in 30 patients (94%) and agenesis in two
      patients (6%). The simple clamp-open distal anastomosis technique was employed in
      the majority of the cases in the single-kidney group (91%) and in the reference
      group (83%); p > 0.05. Renal artery endarterectomy or bypass ipsilateral to
      functioning kidneys was performed on 18 patients (56%) in the single-kidney group
      and 68 patients (12%) in the reference group; p < 0.05. Renal perfusion with cold
      Ringer's lactate solution was done in 18 cases (56%) in the single-kidney group
      and 228 cases (42%) in the reference group; p > 0.05. There was no difference in
      the operative mortality (9% versus 7%) and the incidence of
      paraplegia/paraparesis (6% versus 5%) between the single-kidney group and the
      reference group; p > 0.05. Postoperatively, new onset renal insufficiency
      developed in 10 patients (31%) in the single-kidney group, and 58 patients (11%)
      in the reference group; p < 0.05. In the single-kidney group, four patients (13%)
      had mild renal dysfunction (serum creatinine > or = 2.5 mg/dl), and two patients
      (6%) were on dialysis on discharge. Notably, there was no significant difference
      in the incidence of renal insufficiency on admission compared to the incidence of
      renal insufficiency on discharge in the single-kidney group (13% versus 19%; p >
      0.05). TAAA repair in patients with one functioning kidney can be performed
      safely. Postoperative renal insufficiency can be managed successfully in the
      majority of patients.

PMID- 9514228
TI  - Clinical evidence of contralateral renal parenchymal injury in patients with
      unilateral atherosclerotic renal artery stenosis.
AB  - It has been postulated that the kidney contralateral to a significant renal
      artery stenosis may be at risk for accelerated arteriolar nephrosclerosis. Duplex
      ultrasound is capable of detecting and classifying renal artery stenosis and
      examining parenchymal flow. Renal flow patterns are a reflection of resistance,
      which increases with parenchymal pathology. One-hundred fifty-one patients with
      atherosclerotic renal artery stenosis (ARAS) were prospectively studied with
      duplex ultrasonography. Renal arteries were classified as normal, <60% stenosis,
      > or =60% stenosis, or occluded. The renal artery end-diastolic ratio (EDR) (end
      diastolic velocity/peak systolic velocity) was measured. EDR decreases as
      resistance to flow increases. There were 81 patients with a unilateral > or =60%
      ARAS. The EDR was significantly lower in the kidney contralateral to the > or
      =60% ARAS (0.27 +/- 0.08 versus 0.30 +/- 0.08; p = 0.001, paired t-test). The
      absolute difference in EDR was even more pronounced in the subgroup of 15
      diabetic patients with a > or =60% ARAS (0.22 +/- 0.08 versus 0.27 +/- 0.08; p =
      0.004). This study offers clinical evidence that a unilateral hemodynamically
      significant ARAS is associated with the development of arteriolar nephrosclerosis
      in the contralateral kidney. These results have important implications on blood
      pressure control, renal function, and response to renal revascularization in this
      patient population.

PMID- 9514229
TI  - Primary stenting of atherosclerotic renal artery ostial stenosis.
AB  - Percutaneous transluminal angioplasty for atherosclerotic ostial lesions of the
      renal arteries has resulted in high restenosis rates. Recent reports of
      angioplasty with intravascular stenting show improved results over angioplasty
      alone. The purpose of this study is to review the results of primary stenting of
      ostial renal artery stenosis at our institution. Twenty one patients (11 men, 10
      women, age 63 +/- 11 years), with atherosclerotic renal artery ostial stenosis in
      association with hypertension or renal insufficiency underwent renal angioplasty
      with primary stenting during a 2-year period. Medical records were reviewed for
      indications, technical success, complications, restenosis, response of
      hypertension and response of renal insufficiency. A technical success was defined
      as a normal postprocedure arteriogram with no residual stenosis and no residual
      gradient. Restenosis was defined as > or =60% diameter reduction identified by
      arteriography, or duplex scan demonstrating a renal artery to aortic ratio of >
      or =3.5. Thirty-three stents were placed in 25 arteries with four patients having
      bilateral procedures. All patients were hypertensive. Nine patients (43%) had
      chronic renal insufficiency (creatinine > or =1.5 mg/dl). One patient was on
      hemodialysis. The immediate technical success rate was 95%. Six complications
      occurred in four patients (two pseudoaneurysms, two dissections requiring
      additional stents, renal failure, and atheroembolization). Mean arterial blood
      pressure improved from 117 +/- 13.4 to 103 +/- 12.8 mmHg (p = 0.002) after
      stenting. Serum creatinine levels decreased from 1.48 +/- 0.57 to 1.31 +/- 0.41
      (p = 0.07). Eight patients developed restenosis. The mean follow up was 13 +/- 7
      months. Life table analysis showed a cumulative restenosis rate of 65 +/- 18% at
      24 months. We advise caution in the application of renal stenting for the
      treatment of ostial lesions, particularly in patients for whom standard surgical
      revascularization options are available.

PMID- 9514230
TI  - Is balloon angioplasty indicated for "short" stenoses of failing vein grafts?
AB  - Previous reports have suggested "short" focal stenoses in peripheral vein grafts
      (PVGs), namely less than 2 cm long, can be successfully balloon dilated with good
      long-term patency rates. We questioned if enthusiasm for balloon angioplasty of
      these lesions in failing PVGs is warranted. Between August 1, 1993 and December
      31, 1996, we performed balloon angioplasty of "short" stenoses in 19 PVGs in 16
      patients. Bypasses included seven femoropopliteal, six femorotibial, and six
      popliteal-tibial or -pedal PVGs. All bypasses were originally performed for limb
      salvage. Single lesions were present in 13 grafts and two lesions in six grafts.
      Ten lesions were located at an anastomosis, 10 were located in the body of the
      graft, and five were peri-anastomotic. Fifteen procedures were performed
      percutaneously. Four angioplasties were performed using an open surgical approach
      because a percutaneous attempt failed in one case and three grafts were either in
      situ or tunneled subcutaneously making them easy to expose. Completion
      arteriogram documented excellent initial results in all 19 grafts. Cumulative one
      year primary patency rate was 39%. The assisted primary patency rate at one year
      was 73%. Only five grafts remained patent 7-20 months (mean, 10 months) during
      follow-up without requiring further revision. One patient died with a patent
      graft 23 months post-balloon angioplasty. Complications included two hematomas
      following a percutaneous approach that required surgical repair. These results
      when compared to publications detailing patency following surgical revision
      suggest that balloon angioplasty of "short" stenoses less than 2 cm long in PVGs
      may be better treated by surgical revision. We reserve balloon angioplasty for
      "short" lesions when surgical revision is associated with inordinate difficulty
      such as a scarred groin wound in an obese patient.

PMID- 9514231
TI  - Cost efficacy of duplex surveillance and prophylactic angioplasty of
      arteriovenous ePTFE grafts.
AB  - Poor patency of arteriovenous ePTFE grafts remains a major clinical problem.
      Prophylactic balloon angioplasty of stenoses has been claimed to prolong graft
      patency and has been widely introduced into practice. In this manuscript we
      report the cost incurred in application of such a program involving graft
      surveillance and prophylactic angioplasty of ePTFE graft stenoses >50% diameter.
      All patients in a single dialysis unit with ePTFE bridge grafts were subject to a
      surveillance duplex ultrasound and those with a perigraft stenosis of >50% then
      underwent angiography. Those patients confirmed to have a stenosis >50% within
      the graft, were randomized to prophylactic percutaneous transluminal angioplasty
      (PTA) versus no intervention (observation). Patients were followed every 3 months
      with ultrasound and those in the treatment group with recurrent stenosis (>50%)
      were subject to repeat PTA. The outcome was thrombosis. Relevant charges were
      considered to be: initial duplex screening of the entire ePTFE dialysis group;
      professional and technical fees for angiography and angioplasty; follow-up duplex
      scanning; repeat angioplasty; and costs of lytic therapy for an intraprocedure
      lysis. In the treatment and observation group the 6-month patencies were 69% +/-
      7% and 70% +/- 7%, respectively. Twelve-month patencies for the treatment and
      observation groups were 51% +/- 6% and 47% +/- 4%. There was no significant
      difference between these two groups (p = 0.97), with an 80% confidence limit for
      detection of a difference >20%. Cost for duplex screening of all patients in the
      dialysis unit with ePTFE grafts was $40,440 (@ $337 each x 120 patients). Total
      charges for initial angiography was $178. Angioplasty charges were $143,040. Cost
      of the follow-up duplex ultrasound scanning in the treated group was $32,352.
      Charges for repeat angiograms in those with recurrent stenoses were $83,682
      (professional fee $1733 + $229; technical fee + $820; equipment charges x 32 x
      0.94). One patient required urokinase therapy for an occlusion following PTA. The
      overall charge for treating the 32 patients in the treatment arm of this study
      was $440,834, there was net improvement in patency. A policy of generic graft
      surveillance and prophylactic is expensive and does not lead to improved patency.
      Until an effective intervention is defined by prospective randomized trial,
      surveillance duplex scanning cannot be justified.

PMID- 9514232
TI  - Should vein be saved for future operations? A 15-year review of infrainguinal
      bypasses and the subsequent need for autogenous vein.
AB  - The decision to use prosthetic or autogenous vein as the initial conduit for
      first-time vascular bypass of the lower extremity depends in part on the
      likelihood of subsequent need for autogenous conduit for another leg or heart
      bypass. The true frequency of these later events is not known. To answer this
      question, we analyzed a database of infrainguinal and coronary artery bypasses
      (CABG) performed at one institution between January 1980 and July 1995, to
      determine how many patients required subsequent infrainguinal bypass or CABG
      after their initial leg bypass. Five hundred and seventy-two infrainguinal
      bypasses were performed on 440 patients (mean age 63.9); average follow-up was
      5.6 years. The clinical philosophy favored autogenous vein for first bypass,
      which was used in 84% of first operations performed during the study period while
      prosthetic material was used in 16%. For patients in which vein was used for the
      first operation, and who went on to have a second operation, the use of
      prosthetic conduit rose from 16% of operations to 27% (p < 0.05). The rate of
      subsequent CABG after leg bypass was very low, 2% at 5 years, 3% at 10 years. The
      cumulative probability of requiring a subsequent infrainguinal bypass was 27% at
      5 years, 32% at 10 years. Of these, 46% were ipsilateral and 54% were
      contralateral. Considering only subsequent tibial bypasses (where vein might be
      considered obligatory), the cumulative 5-year rate of subsequent leg bypass was
      only 13%. Another bypass was most likely to occur within the first 3 years,
      rarely thereafter. In summary, after primary infrainguinal bypass, additional
      procedures using vein may arise in 1/4 to 1/3 of patients, mostly in the first 3
      years. However, only 13% will definitely need vein for tibial bypass in 5 years,
      and subsequent CABG is uncommon.

PMID- 9514233
TI  - Do distal arteriovenous fistulae improve patency rates of prosthetic
      infrapopliteal arterial bypasses?
AB  - We retrospectively analyzed if distal anastomotic adjunctive arteriovenous
      fistulae (AVF) improved patency rates of prosthetic bypasses to infrapopliteal
      arteries. Between July 1, 1991 and June 30, 1996, we performed 43
      polytetrafluoroethylene (PTFE) bypasses to infrapopliteal (19 peroneal, 13
      anterior tibial, 11 posterior tibial) arteries. All bypasses were performed for
      limb salvage when autologous vein was not available for a conduit. Adjunctive
      AVFs were performed in 21 bypasses (PTFE-AVF) and 22 bypasses did not have a
      fistula (PTFE-ONLY). Patients were allocated to the PTFE-AVF or PTFE-ONLY groups
      at the discretion of the surgeons, with adjunctive AVFs being performed for small
      arteries with poor run-off. There were no significant differences in age, sex,
      site of the proximal anastomosis, or indication for surgery (p > 0.05). There
      were statistically significant differences in the site of distal anastomosis and
      quality of arterial run-off based on the Society for Vascular Surgery Ad Hoc
      Committee on Reporting Standards criteria (p < 0.05). All patients were placed on
      heparin 500 units/hour postoperatively, maintained on life-long Coumadin and
      followed every 3 months with duplex ultrasonography to assess graft patency.
      Aggressive intervention was carried out for failing grafts suspected by duplex
      scanning. The hospital mortality rate was 2.3% (1/43; 1 PTFE-AVF). Two-year
      primary patency rates were significantly better for PTFE-AVF grafts than for PTFE
      ONLY grafts (23% versus 5%) (p = 0.04). Although statistical significance was not
      reached, there was a suggestion of higher assisted primary (34% versus 15%) (p >
      0.05) and secondary (61% versus 48%) (p > 0.05) patency rates in the PTFE-AVF
      group versus the PTFE-ONLY group, although limb salvage rates were similar (74%
      versus 71%) (p > 0.05). Two AVFs required ligation because of steal resulting in
      diminished distal perfusion. These results support the use of adjunctive distal
      AVFs to improve overall two-year patency rates of prosthetic infrapopliteal
      arterial bypasses.

PMID- 9514234
TI  - The valvular apparatus in venous insufficiency: a problem of quantity?
AB  - Abnormal venous valvular function may produce venous reflux and venous
      insufficiency. While valvular agenesis is a known, but rare cause of venous
      insufficiency. While valvular agenesis is a known, but rare cause of venous
      insufficiency, little work has been done on the relative number of greater
      saphenous vein (GSV) valves in patients with venous insufficiency. This study
      investigates whether the GSV in patients with symptomatic venous insufficiency
      has fewer valves than the GSV of patients without venous insufficiency. The
      number of GSV valves in patients (n = 51) with symptomatic venous insufficiency
      undergoing saphenectomy (VI) were compared with the number of GSV valves in
      patients (n = 26) without venous insufficiency undergoing in situ GSV bypass
      under angioscopic surveillance who served as a control group. The two groups
      differed, as expected, in age and sex distribution. The VI group had a mean of
      25.7 +/- 11.0 centimeters of GSV between valves, while the control group had 19.0
      +/- 9.7 centimeters of GSV between valves (F = 6.99; p = 0.01). The mean number
      of valves in the saphenous veins of the two groups also differed significantly:
      VI = 2.3 +/- 0.83 versus control (CTRL) = 4.8 +/- 2.01 (F = 61.86; p < 0.0001).
      That properly functioning valve leaflets help maintain physiologic antegrade
      venous flow is indisputable. This study, however, suggests that the relative lack
      of valves may be related to the development of venous insufficiency. This report
      documents that patients with symptomatic reflux in the GSV have significantly
      fewer valves than patients with apparently normal functioning saphenous veins.

PMID- 9514235
TI  - Carotid endarterectomy: the mandate for high quality duplex.
AB  - Excellent correlation between carotid angiography and duplex scanning has made it
      possible to perform carotid endarterectomy without angiography. The accuracy of
      scans from practices without a dedicated vascular laboratory must be validated
      prior to their use for clinical decisions. Seventy six patients had a carotid
      duplex performed at an outside institution and were referred for vascular
      surgery. All patients underwent a repeat study at our dedicated vascular lab. The
      overall accuracy of our lab was 93.8% for all carotid categories as demonstrated
      by angiography. Outside carotid duplex reports correlated with repeat exams as
      follows: occlusions: 10/13 carotids (76.9%); 80%-99% stenoses: 15/39 carotids
      (38.5%); 50%-79% stenoses: 28/44 carotids (63.6%). If a surgeon's practice is to
      operate for asymptomatic 80%-99% stenoses by report, then unnecessary surgery
      might have been performed in 61.5% of these carotids and appropriate surgery
      denied in 3.6%. Outside duplex velocities consistent with a 60%-99% stenosis
      correlated in 13/17 carotids (76.5%). If a surgeon's practice is to operate for
      asymptomatic 60%-99% stenoses based on velocity criteria, then unnecessary
      surgery might have been performed in 23.5% of these carotids, and appropriate
      surgery denied in 7.6% placing these patients at increased risk of stroke.
      Outside scans significantly overestimated the severity of carotid disease (p =
      0.003). The weighted kappa analysis for agreement between scans was only 60.2%.
      Failure to have validated high-quality duplex in labs performing carotid studies
      can lead to unnecessary angiography or surgery. Carotid endarterectomy without
      angiography should be performed only when duplex accuracy has been previously
      validated by angiographic correlation studies. Poor agreement with studies from
      practices without a dedicated vascular lab makes it mandatory to repeat the
      duplex on all patients prior to clinical decision making. Reimbursement for such
      repeat studies should not be denied.

PMID- 9514236
TI  - Anesthetic methods in reoperative carotid surgery.
AB  - It has been suggested that general anesthesia is the preferred method for
      reoperative carotid surgery for several reasons, including: the difficulty of the
      reoperative dissection; the disease may extend unusually high into the internal
      carotid artery; and the reconstruction required may be more complex than a
      typical endarterectomy. The purpose of this study is to show that reoperative
      carotid surgery can be performed safely under regional anesthesia. The records of
      109 reoperative carotid operations performed on 96 patients over the past 25
      years were reviewed. Procedures performed under regional anesthesia were compared
      to those performed under general anesthesia with respect to patient
      characteristics, intraoperative courses, and perioperative results. Regional
      anesthesia was utilized in 79 operations (72.5%); 30 operations were performed
      with general anesthesia (27.5%). The two patient groups were essentially
      equivalent with regard to atherosclerotic risk factors, preoperative neurologic
      symptoms, and the prevalence of contralateral total occlusion. The etiologies for
      recurrent disease included recurrent atherosclerosis (50.4%), intimal hyperplasia
      (30.3%), and vein patch aneurysm (9.2%). The methods of reconstruction employed
      included saphenous vein patch (47.7%), vein interposition graft (11.9%),
      prosthetic patch (20.2%), and prosthetic graft (20.2%). Perioperative strokes
      occurred in one case performed under regional anesthesia (1.3%), and in two cases
      under general anesthesia (6.6%); this difference was not statistically
      significant. Reoperative carotid artery surgery can be performed under regional
      anesthesia safely in the majority of instances. The aforementioned theoretical
      factors in favor of general anesthesia could also lead to technical difficulties
      with intraarterial shunt insertion. Having the patient awake, even if just long
      enough to prove that the patient will tolerate carotid artery clamping, might
      simplify many of these operations by avoiding shunt insertion. Regional
      anesthesia should therefore be considered an acceptable option in cases of
      reoperative carotid surgery.

PMID- 9514237
TI  - Hypercholesterolemia alters the gene expression of novel components of the
      extracellular matrix in experimental vein grafts.
AB  - The success rate of vascular bypass procedures is limited by the development of
      intimal hyperplasia (IH). Hypercholesterolemia has been shown to accelerate IH in
      both arteries and experimental vein grafts; however the mechanism remains
      uncertain. Hyaluronic acid synthase (HAS-1) is a transmembrane enzyme responsible
      for the formation of hyaluronan; an important constituent of extracellular matrix
      (ECM). The integrin receptor for hyaluronan is CD-44. Both CD-44 and HAS-1 have
      been studied in the development of ECM of wounds but have yet to be examined in
      the ECM of IH within vein grafts. The purpose of this study was to determine if
      the expression of CD-44 and HAS-1 is increased during the early stages of IH and
      how cholesterol supplementation affects these genes. Forty white male New Zealand
      rabbits were divided into two groups: cholesterol supplemented (1% cholesterol
      chow) and noncholesterol supplemented. Each set of 20 rabbits was then divided
      into four additional groups (n = 5); a nonoperative group (control) and three
      operative groups that underwent a right interposition carotid bypass using
      jugular vein. Grafts were harvested at 3, 7, and 21 days after surgery for
      molecular studies and histology. Ribonuclease protection assays were performed
      using 32P-labeled riboprobes for HAS-1, CD-44, and 18s rRNA. Densitometric
      analysis is expressed as a ratio (riboprobe/rRNA). Cholesterol levels differed
      significantly between cholesterol supplemented and nonsupplemented groups (1419
      +/- 130 mg/dl and 48 +/- 12 mg/dl) (p < 0.01). There was a significant increase
      in the expression of HAS-1 and CD-44 in the vein grafts compared to normal
      jugular vein. Cholesterol supplementation caused a further increase in CD-44 gene
      expression versus nonsupplemented vein grafts. These data demonstrate a role for
      CD-44 and HAS-1 transcription in vein graft intimal hyperplasia, which is further
      altered by cholesterol supplementation. Lastly, these results could explain
      differences seen in the development of IH with hypercholesterolemia and
      ultimately provide for improved therapies in alleviating this process.

PMID- 9514238
TI  - Cigarette smoking alters the rabbit transarterial wall oxygen gradient.
AB  - The objective of this study is to determine the effect of short-term (3 weeks)
      and long-term (10 weeks) cigarette smoking on the transarterial wall oxygen
      gradient. Female New Zealand White Rabbits (3-4 kg) were exposed to the smoke of
      seven nonfiltered cigarettes daily and their transarterial wall oxygen gradients
      measured at 3 weeks or 10 weeks before and during cigarette smoke exposure.
      Arterial blood oxygen content, percent of carboxyhemoglobin, and arterial blood
      pressure were recorded during the experiments. Short-term cigarette smoking
      resulted in a decrease in the artery wall oxygen content only during exposure to
      cigarette smoke that corresponded to arterial blood hypoxia. Long-term cigarette
      smoke exposure resulted in a sustained decrease in artery wall oxygen content
      noted 24 hours after last exposure to cigarette smoke with normal levels of
      arterial blood oxygen and an acute decrease during cigarette smoke exposure with
      corresponding arterial blood hypoxia. These results were noted despite no
      differences in blood pressure or evidence of atherosclerotic lesions. Short-term
      cigarette smoking results in artery wall hypoxia only during cigarette smoke
      exposure and arterial blood hypoxia while long-term cigarette smoking results in
      sustained artery wall hypoxia in the presence of normal arterial blood oxygen
      content.

PMID- 9514239
TI  - The contributions of arterial and venous volumes to increased cutaneous blood
      flow during leg compression.
AB  - Intermittent lower extremity compression increases cutaneous blood flow. The
      source of this increased perfusion and, the influence of physical activity on
      stimulated foot skin perfusion has not been elucidated. The purpose of this study
      is to determine the arterial and venous contributions to augmented cutaneous
      blood flow during foot and leg compression, and to evaluate whether physical
      activity influenced the response to compression. Fifty limbs from 29 normal
      volunteers were studied in the sitting position. Their daily physical activity
      was categorized as active if they exercised > or =3 days/week or sedentary if
      they exercised < or =3 days/week. Inflatable foot and calf compression cuffs
      attached to a timed-pressure pump (Art-assist AA 1000, ACI, Inc., San Marcos, CA)
      were applied to the subject's leg and set to deliver 120 mmHg pressure with a 10
      sec deflation cycle. Skin perfusion of the great toe was recorded by a laser
      Doppler (Laserflo Model BPM 403, TSI, Inc., St. Paul, MN). Total perfusion with
      compression (A), retrograde venous perfusion (B), and compression artifact (C)
      was recorded. Mean values for A, B, and C and the differences between the two
      groups were analyzed using multivariate multiple comparison statistical method.
      The mean baseline skin perfusion was 3.96 +/- 0.91, and mean total stimulated
      skin perfusion (A) was 9.23 +/- 2.13. With arterial inflow obliterated and
      compression applied, mean skin perfusion (B) was 1.96 +/- 0.44. The sedentary
      group had a mean resting perfusion of 1.64 +/- 0.28 and mean stimulated value (A)
      of 2.29 +/- 0.37 ml/min/100 gm tissue. The active group had a mean resting
      perfusion of 28.26 +/- 0.91, and stimulated value (A) of 32.65 +/- 4.47
      ml/min/100 gm tissue. These differences in the mean skin perfusion between the
      two groups were significant. It is concluded that in normals, the majority of
      increased perfusion is from increased arterial inflow. There is a larger resting
      foot skin perfusion in active individuals and they have quantitatively greater
      stimulated inflow compared to sedentary individuals.

PMID- 9514240
TI  - Operative management of acute mesenteric ischemia. Part 1.

PMID- 9514241
TI  - Signal transduction within G-protein coupled receptors via an ion tunnel: a
      hypothesis.
AB  - Based on molecular modeling of the complexes between the mu-opioid receptor and
      its ligands, we present a hypothesis that accounts for several of the
      experimental data including the importance of conserved polar residues in
      rhodopsin-like G-protein-coupled receptors and the effect of Na+ on the binding
      of ligands to these receptors. We propose that agonists, but not antagonists,
      would displace Na+ from its initial binding site at the conserved D2.50 residue
      in the second transmembrane alpha-helical segment, H2. The displaced Na+ would
      pass through a "gate" of conserved hydrophobic residues and move along a tunnel
      like interface (formed of H2, H3 and H7) enriched with several conserved
      hydrophilic residues including D3.49. Interaction of Na+ with D3.49 would result
      in the breaking of a salt-bridge between D3.49 and the conserved R3.50 residue
      thus exposing the latter for interaction with the G-protein.

PMID- 9514242
TI  - Conformational analysis of the highly potent bradykinin antagonist Hoe-140 by
      means of two different computational methods.
AB  - The AMBER 4.0 force field was used to perform the characterization of the
      conformational profile of the highly potent bradykinin antagonist Hoe-140 (D-Arg0
      Arg1-Pro2-Hyp3-Gly4-Thi5-Ser6-D-++ +Tic7-Oic8-Arg9). The structural features of
      the peptide were assessed using two different computational methods, both capable
      to provide a good sampling of the low-energy conformations of the molecule.
      Specifically, the conformational space of the peptide was explored: i) computing
      molecular dynamics trajectories in cycles of high (900 K) and low (300 K)
      temperature and ii) using simulated annealing (SA) in an iterative fashion.
      Analysis of the structures characterized indicates that most of the low-energy
      conformations of the peptide exhibit a betaII'-turn motif at its C-terminus, in
      agreement with previous experimental and theoretical studies. On the other hand,
      about a 50% of the low-energy conformations characterized also exhibit different
      beta-turn type motifs at the N-terminus, whereas the rest of the conformations
      can be described as bends. Finally, in order to get new insights into the
      structural requirements necessary to design more potent and selective antagonists
      of bradykinin, present results were compared with those previously reported by
      this laboratory on the conformational preferences of the native nonapeptide and
      its DPhe7 analog.

PMID- 9514243
TI  - Structural features of helical aggregates of antibacterial peptides via simulated
      annealing and molecular modeling.
AB  - A 27-residue stretch of amino acids encompassing two putative 13-residue
      amphiphilic helical segments is an important determinant of activity in the 47
      residue antibacterial peptide bovine seminalplasmin. Synthetic peptides
      corresponding to the 27-residue stretch (P27) SLSRYAKLANRLANPKLLETFLSKWIG as well
      as the 13-residue segments PKLLETFLSKWIG (SPF),exhibit antimicrobial activity. An
      analog of SPF where E has been replaced by K(SPFK) showed improved antimicrobial
      properties as compared to SPF. The peptides have the ability to bind and
      permeabilize membranes. We have modeled helical bundles of P27 and the two 13
      residue peptides SPF and SPFK using simulated annealing via molecular dynamics.
      Octameric but not hexameric aggregates of P27 can form channels which would allow
      the passage of ions. In the case of 13-residue peptides, aggregates formed by 6
      monomers can conceivably form ion conducting channels. Since the ability to form
      channels which would allow the passage of ions across the membranes is an
      important determinant of the biological activities of these peptides, knowledge
      of the pore forming structures should help in the design of analogs with improved
      activities.

PMID- 9514244
TI  - Modeling of Entamoeba histolytica ferredoxin.
AB  - The E. histolytica ferredoxin (EHFXD) is an iron-sulphur protein and is important
      in the control of E. histolytica because it donates an electron to and activates
      metronidazole (4) the most effective anti-amoebic drug. The knowledge of the
      three-dimensional structure of EHFXD can help to assist in rational design of
      anti-amebic drugs. Homology modeling of EHFXD has been done by using the
      knowledge of crystal structure of homologous Ferredoxin structures. It has been
      shown that EHFXD is more likely to contain 2[4Fe-4S] clusters and has a
      pseudodiad symmetrical fold. The fold is stabilised by hydrophobic patches as
      well as by intramolecular hydrogen bonds. The importance of two Leu residues in
      the N- and C-termi in bridging the two clusters has been emphasised. The
      electrostatic properties of the surface of EHFXD were examined and compared with
      that of other ferredoxins. It was observed that large regions of negative as well
      as positive electrostatic potential is a common feature of the [4Fe-4S]
      containing ferredoxins which might explain their biological role as both electron
      acceptor and electron donor molecules.

PMID- 9514245
TI  - A new method to characterize hydrophobic organization of proteins: application to
      rational protein engineering of barnase.
AB  - We present a new algorithm for characterization of protein spatial structure
      basing on the molecular hydrophobicity potential approach. The method is
      illustrated by the analysis of three-dimensional structure of barnase and barnase
      barstar complex. Current approach enables identification of amino acid residues
      situated in unfavorable environment (these residues may be "active" for binding),
      and to map quantitatively hydrophobic, hydrophilic and unfavorable hydrophobic
      hydrophilic intra- and inter-molecular contacts involving backbone and side-chain
      segments of amino acid residues. Calculation of individual contributions of amino
      acid residues to such contacts permits identification of structurally-important
      residues. The contact plots obtained with molecular hydrophobicity potential
      calculations, provide easy rules to choose sites for mutations, which can
      increase a strength of intra- or inter-molecular hydrophobic interactions. The
      unfavorable hydrophobic-hydrophilic contact can be mutated to favorable
      hydrophobic, and already existing weak hydrophobic contact can be strengthen by
      increasing hydrophobicity of residues in contact. Basing on the analysis of the
      contact plots, we suggest several mutations of barnase which are supposed to
      increase intramolecular hydrophobic interactions, and thus might lead to
      increased stability of the protein. Part of these mutations was studied
      previously experimentally, and indeed stabilized barnase. The other of predicted
      mutations were not studied experimentally yet. Several new mutations of barnase
      and barstar are also proposed to enhance the hydrophobic interactions on their
      binding interface.

PMID- 9514246
TI  - Statistical and structural analysis of trp binding sites: comparison of natural
      and in vitro selected sequences.
AB  - Two different modes can be used when the trp repressor binds to trp binding
      sites. In the "full-site mode" each repressor molecule is bound to a DNA target
      containing at least two conserved five base pair tracts separated by eight base
      pairs. The binding of the repressor to natural trp operators is of this kind. In
      the "half-site mode" two repressor molecules are sequence-specifically bound,
      with infinite cooperativity, to two abutting DNA pentamers. We present evidence
      suggesting that the sequences obtained by a recent in vitro selection assay
      (Czernik et al. J. Biol. Chem. 269, 27869-27875, 1994) were selected by the
      binding of two repressor molecules, and that the repressor is bound to most of
      these sequences using the half-site mode. Using the results of the selection
      assay, and the set of natural trp binding sites, we characterize the different
      sequence requirements of the "full-site" versus the "half-site" binding modes. A
      statistical analysis of the information content of these binding sites shows that
      functional information on protein binding modes can be extracted from a set of
      DNA binding sites by comparing the information content of two different DNA
      populations, or sub-populations. Furthermore, it shows that the binding of
      proteins to sequences selected by a functional in vitro assay do not necessarily
      mimic the binding of the protein to the natural targets, even if the information
      content is similar in the two DNA target populations, i.e., even if the
      stringency of the selection assay is adequate for locating natural-like
      sequences. In addition, we show that the structural requirements for protein-DNA
      interactions can be achieved by different conformations at the base-pair level.
      Differences in the structural characteristics of different base-pair steps can be
      used to determine the binding mode and differential binding affinity, which can
      be utilized in the regulation of several binding sites by a single specific
      protein.

PMID- 9514247
TI  - Modeling of reaction steps relevant to deoxyuridylate (dUMP) enzymatic
      methylation and thymidylate synthase mechanism-based inhibition.
AB  - Theoretical quantum mechanical ab initio Hartree-Fock calculations on molecular
      systems, modeling processes related to the specificity of thymidylate synthase
      inactivation are reported. We considered several steps of the methylation of the
      substrate dUMP and 4- or 5-mono- and 4,5-bisubstituted dUMP analogs, as well. The
      following reactions were modeled: the cysteine residue (Cys198 in the L.casei
      enzyme) nucleophilic attack on the substrate and the substrate C(5)-H proton
      abstraction. The substrate was modeled by the 1-methyluracil molecule and its
      structural analogs. The cysteine Cys198 residue was modeled by the
      methylmercaptane molecule. The substrate-enzyme binary complex was modeled by the
      1-methyl-5,6-dihydro-6-thiomethyl-uracil (P1) molecule. The present theoretical
      calculations suggest that the cysteine nucleophilic attack on the substrate may
      result in the SH-group addition to the pyrimidine C(5)=C(6) bond in the course of
      a weakly exothermic reaction. The formerly presumed enolate carbanion appeared to
      be weakly stable or unstable and it can readily split into the thiol and
      pyrimidine residues. The s2-thio- (P2) and s2,4-dithio- (P3) substrate analogs
      should form stable thiolate anions after cysteine residue attachment to the C(6)
      position of the pyrimidine ring. Studies of the deformed P1 molecule interacting
      with a water molecule bound to the pyrimidine C(4)=O carbonyl residue allow a
      suggestion that this water molecule may be directly involved in the C(5)-H proton
      abstraction and may serve as a proton transmitter between the substrate and the
      proton acceptor residue, possibly located on the cofactor N10-nitrogen.
      Interaction of the pyrimidine C(4)=O group, or its modification, with the N5,10
      methylenetetrahydrofolate N(10) nitrogen atom is suggested as an additional
      factor influencing the inhibition process.

PMID- 9514248
TI  - Mammalian retroposons integrate at kinkable DNA sites.
AB  - Integration of retroposed RNA in mammals occurs at staggered breaks resulting
      from an enzyme-generated pair of nicks at opposite DNA strands, preferably within
      15-16 bp. Although consensus sequences associated with the two nicks appear
      somewhat different from one another, both nicking sites are rich in TA, CA and TG
      dinucleotide steps which are known as specific DNA sites where kinks may occur
      under bending constraints. This suggests that during interaction with the
      endonucleolytic enzyme, or enzymes, DNA undergoes bending at the integration
      sites and kinks are formed, as initial steps in generating the nicks. Nicking at
      kinkable sites, particularly at TA steps, may also play a role in integration of
      other insertion elements.

PMID- 9514249
TI  - Solution structures of the Huntington's disease DNA triplets, (CAG)n.
AB  - Highly polymorphic DNA triplet repeats, (CAG)n, are located inside the first exon
      of the Huntington's disease gene. Inordinate expansion of this repeat is
      correlated with the onset and progression of the disease. NMR spectroscopy, gel
      electrophoresis, digestion by single-strand specific P1 enzyme, and in vitro
      replication assay have been used to investigate the structural basis of (CAG)n
      expansion. Nondenaturing gel electrophoresis and 1D 1H NMR studies of (CAG)5 and
      (CAG)6 reveal the presence of hairpins and mismatched duplexes as the major and
      minor populations respectively. However, at high DNA concentrations (i.e., 1.0
      2.0 mM that is typically required for 2D NMR experiments) both (CAG)5 and (CAG)6
      exist predominantly in mismatched duplex forms. Mismatched duplex structures of
      (CAG)5 and (CAG)6 are useful, because they adequately model the stem of the
      biologically relevant hairpins formed by (CAG)n. We, therefore, performed
      detailed NMR spectroscopic studies on the duplexes of (CAG)5 and (CAG)6. We also
      studied a model duplex, (CGCAGCG)2 that contains the underlined building block of
      the duplex. This duplex shows the following structural characteristics: (i) all
      the nucleotides are in (C2'-endo, anti) conformations, (ii) mismatched A x A base
      pairs are flanked by two Watson-Crick G x C base pairs and (iii) A x A base pairs
      are stably stacked (and intra-helical) and are formed by a single N6-H--N1
      hydrogen bond. The nature of A x A pairing is confirmed by temperature-dependent
      HMQC and HMQC-NOESY experiments on the [(CA*G)5]2 duplex where the adenines are
      15N-labeled at N6. Temperature- and pH-dependent imino proton spectra,
      nondenaturing electrophoresis, and P1 digestion data demonstrate that under a
      wide range of solution conditions longer (CAG)n repeats (n> or =10) exist
      exclusively in hairpin conformation with two single-stranded loops. Finally, an
      in vitro replication assay with (CAG)8,21 inserts in the M13 single-stranded DNA
      templates shows a replication bypass for the (CAG)21 insert but not for the
      (CAG)8 insert in the template. This demonstrates that for a sufficiently long
      insert (n=21 in this case), a hairpin is formed by the (CAG)n even in presence of
      its complementary strand. This observation implies that the formation of hairpin
      by the (CAG)n may cause slippage during replication and thus may explain the
      observed length polymorphism.

PMID- 9514250
TI  - Hairpin induced slippage and hyper-methylation of the fragile X DNA triplets.
AB  - The fragile X triplet repeats, (GCC)n x (GGC)n are located at the 5' untranslated
      region of the FMR-1 gene. Inordinate repeat expansion and hyper-methylation of
      the CpG islands inside the repeat lead to the suppression of the FMR-1 gene and
      the subsequent onset and progression of the disease. Previously, we have shown
      that the (GCC)n strand of the fragile X repeat readily forms hairpin structures
      under physiological conditions (Chen et al., Proc. Natl. Acad. Sci. USA, 92:5199
      5203, 1995: Mariappan et al., Nucl. Acid Res. 24:784-792, 1996). Here, we show by
      an in vitro assay that formation of the (GCC)n hairpins leads to slippage during
      replication. The slippage structure is a three-way junction with two Watson
      Crick, (GCC)n x (GGC)n, arms and a third (GCC)n hairpin arm. Formation of such
      slippage structures during replication may explain the observed length
      polymorphism of the fragile X repeat. We have also studied the substrate
      efficiency of these three-way junctions toward the human methyltransferase. the
      enzyme that methylates the CpG sites in DNA. These methylation studies show that
      the slippage structures induced by the (GCC)n hairpins are 10-15 times more
      efficient substrates than either the corresponding Watson-Crick duplexes or the
      (GCC)n hairpins. We demonstrate by appropriate designs that the exceptional
      substrate efficiency of the three-way junction slippage structures is due to two
      factors: (i) the presence of the (GCC)n hairpin in which CpG sites are more
      accessible for methylation than the CpG sites in the Watson-Crick duplex and (ii)
      the ability of the (GCC)n hairpin in these three-way junctions to move along the
      Watson-Crick arms that facilitates conversion of low-affinity Watson-Crick CpG
      sites into high-affinity hairpin CpG sites. Therefore, we suggest that the
      formation of the (GCC)n hairpins during replication can explain both length
      polymorphism and hyper-methylation of the fragile X repeats.

PMID- 9514251
TI  - Toroidal structures due to anisotropy of DNA-like molecules.
AB  - We suggest that toroidal structures in the state of psi-condensation of DNA may
      be caused by anisotropy on a meso-scale of several thousand A, the conformation
      of a DNA-molecule being determined by its elasticity and neutralization of
      phosphate charge. We model a molecule of B-DNA on an anisotropic elastic rod
      subject to a torque, and make the numerical simulation of the model that reveals
      that under appropriate conditions, which may be effected in experimental setting
      by changing the concentration of polymeric solutions, there are toroidal
      structures having the size of a few persistence lengths, in agreement with the
      experimental data. On changing the elastic modulii or characteristics of the
      counterion layer, we see the toroidal structures turn into the spherical ones. To
      understand the function of anisotropy it would be interesting to investigate the
      Z-DNA as regards psi-condensation.

PMID- 9514252
TI  - The opening of a single base without perturbations of neighboring nucleotides: a
      study on crystal B-DNA duplex d(CGCGAATTCGCG)2.
AB  - In this work we explore the possibility of the opening of a single base without
      perturbation of its neighboring nucleotides. Low energy base opening into the
      grooves can be accomplished by rotation of the relevant backbone and glycosidic
      bond torsion angles. The pathway has been determined by identifying zeta torsion
      angle as the reaction coordinate together with the accompanying geometric
      requirement that guides the displacement of other torsion angles. Our study on
      Dickerson dodecamer duplex d(CGCGAATTCGCG)2 showed that all bases with normal
      equilibrium zeta can be rotated by approximately 30 degrees, corresponding to
      approximately 3.5A base displacement, towards the major groove. Such an opening
      extent is comparable with estimated amplitudes of local angular motions in DNA
      bases from NMR experiments, which might facilitate proton exchange. The computed
      base opening energy barrier is also comparable with measured base pair opening
      enthalpy. These results indicate possible relevance of the pathway studied in
      this work with experimentally observed base pair opening process. Our analysis
      also showed a preference for base opening along the major groove and an abnormal
      opening behavior for bases with unusual equilibrium zeta torsion angle.

PMID- 9514253
TI  - Multimode interaction of Hoechst 33258 with eukaryotic DNA; quantitative analysis
      of the DNA conformational changes.
AB  - The interaction of the minor groove binding ligand Hoechst 33258 (Hoe) with
      natural DNA was investigated by high resolution titration rotational viscometry.
      Analysis of the concomitant DNA conformational changes was performed with two DNA
      samples of sufficiently different molar mass M, at 4 degrees C, 22 degrees C and
      40 degrees C, for Hoe/DNA-P ratios below r = 0.02. In this narrow r range several
      interaction modes could be resolved. The measured conformational changes were
      quantified in terms of relative changes of both apparent DNA persistence length,
      delta a/a, and hydrodynamically operative DNA contour length, deltaL/L. Delta
      a/a(r) primarily is a measure of ligand-induced DNA helix stiffening, but both,
      delta a/a(r) and deltaL/L(r), generally depend also on ligand binding induced DNA
      bending or DNA unbending. The essential difference obviously is that delta a/a(r)
      is influenced by the randomly distributed helix bends and deltaL/L(r) by phased
      ones. The measurements performed at different temperatures deliver informations
      about existence and temperature dependent abolition of intrinsic helix curvature.
      Both Hoe and netropsin (Nt) prefer binding to AT rich DNA segments, which are
      candidates for intrinsic DNA helix bends. But our data for Hoe interaction with
      calf thymus DNA (ctDNA) show characteristic differences to those for Nt-ctDNA
      interaction. Especially for Hoe, the mode of highest affinity is saturated
      already at a ligand concentration of roughly 1 nM (r approximately = 0.0015
      Hoe/DNA-P). It exhibits an unusually strong temperature dependence of the
      conformational DNA response. A Hoe-Nt competition experiment shows that Hoe
      binding to the sites of the very first Hoe mode is almost unaffected by bound Nt.
      But Hoe binding to the sites of the following Hoe modes does not occur due to the
      competition with Nt. Thus this mode of strongest Hoe-DNA interaction reflects a
      unique mechanism, possibly of high relevance for gene regulatory systems.

PMID- 9514254
TI  - Preference for syn conformation: crystal structures of free acid and ammonium
      salt of adenosine 2'-monophosphate: an inhibitor of RNase T1.
AB  - This paper reports the crystal structures of free acid and ammonium salt of
      adenosine 2'-monophosphate (2'-AMP). 2'-AMP crystallizes in the hexagonal space
      group P6(5)22 with a = 9.530(3) A, c = 73.422(2) A, and Z= 12. 2'-AMP.NH4
      crystallizes in the trigonal space group P3(1) with a = 9.003(2) A, c = 34.743(2)
      A and Z= 6. Both the structures were solved by direct methods and refined by full
      matrix least- squares method to final R factors of 0.080 and 0.038 for 2'-AMP and
      2'-AMP.NH4 respectively. The adenine bases of both the structures are in syn
      conformation contrasting with the anti geometry in 3'-AMP, 5'-AMP and the enzyme
      bound state. Ribose moiety of 2'-AMP is in C2' -endo conformation. However, the
      ribose moieties of both the nucleotide molecules display C2'-endo-C3'-exo twist
      conformation in 2'- AMP.NH4 structure. Both structures demonstrate g+
      conformation about C4' -C5' bond. 2'-AMP and one of the nucleotide molecules of
      2'-AMP.NH4 are protonated at N1 and the ammonium ion is involved in a bifurcated
      hydrogen bond with O3' B and O3A atoms. A characteristic feature of both the
      structures is the intramolecular O5' -N3 hydrogen bond. Our crystallographic
      results on 2'-AMP corroborates the earlier conclusion that the enzyme-bound state
      is not the lowest energy state of this nucleotide. 2' -AMP displays base-ribose
      04' stacking not seen in the 2'-AMP.NH4 structure. Theoretical and experimental
      studies on 2'-, 3'- and 5'-AMP structures have been discussed.

PMID- 9514255
TI  - Metal-nucleotide interactions: crystal structures of alkali (Li+, Na+, K+) and
      alkaline earth (Ca2+, Mg2+) metal complexes of adenosine 2'-monophosphate.
AB  - Crystal structures of lithium, sodium, potassium, calcium and magnesium salts of
      adenosine 2'-monophosphate (2'-AMP) have been obtained at atomic resolution by X
      ray crystallographic methods. 2'-AMP.Li belongs to the monoclinic space group
      P2(1) with a = 7.472(3)A, b = 26.853(6) A, c = 9.184(1)A, b = 113.36(1)A and Z=
      4. 2'-AMP.Na and 2'-AMP.K crystallize in the trigonal space groups P3(1) and
      P3(1)21 with a = 8.762(1)A, c = 34.630(5)A, Z= 6 and a = 8.931(4), Ac =
      34.852(9)A and Z= 6 respectively while 2'-AMP.Ca and 2'-AMP.Mg belong to space
      groups P6(5)22 and P2(1) with cell parameters a = 9.487(2), c = 74.622(13), Z =
      12 and a = 4.973(1), b = 10.023(2), c = 16.506(2), beta = 91.1(0) and Z = 2
      respectively. All the structures were solved by direct methods and refined by
      full matrix least-squares to final R factors of 0.033, 0.028, 0.075, 0.069 and
      0.030 for 2'-AMP.Li, 2'-AMP.Na, 2'- AMP.K, 2'-AMP.Ca and 2'-AMP.Mg, respectively.
      The neutral adenine bases in all the structures are in syn conformation
      stabilized by the O5'-N3 intramolecular hydrogen bond as in free acid and
      ammonium complex reported earlier. In striking contrast, the adenine base is in
      the anti geometry (chiCN = -156.4(2)degrees) in 2'-AMP.Mg. Ribose moieties adopt
      C2'-endo puckering in 2'-AMP.Li and 2'-AMP.Ca, C2'-endo-C3'-exo twist puckering
      in 2'-AMP.Na and 2'-AMP.K and a C3'-endo-C2'-exo twist puckering in 2'-AMP.Mg
      structure. The conformation about the exocyclic C4'-C5' bond is the commonly
      observed gauche-gauche (g+) in all the structures except the gauche- trans (g-)
      conformation observed in 2'-AMP.Mg structure. Lithium ions coordinate with water,
      ribose and phosphate oxygens at distances 1.88 to 1.99A. Na+ ions and K+ ions
      interact with phosphate and ribose oxygens directly and with N7 indirectly
      through a water oxygen. A distinct feature of 2'-AMP.Na and 2'-AMP.K structures
      is the involvement of ribose 04' in metal coordination. The calcium ion situated
      on a two-fold axis coordinates directly with three oxygens OW1, OW2 and O2 and
      their symmetry mates at distances 2.18 to 2.42A forming an octahedron. A classic
      example of an exception to the existence of the O5'-N3 intramolecular hydorgen
      bond is the 2'-AMP.Mg strucure. Magnesium ion forms an octahedral coordination
      with three water and three phosphate oxygens at distances ranging from 2.02 to
      2.11 A. A noteworthy feature of its coordination is the indirect link with N3
      through OW3 oxygen resulting in macrochelation between the base and the phosphate
      group. Greater affnity of metal clays towards 5' compared to 2' and 3'
      nucleotides (J. Lawless, E. Edelson, and L. Manning, Am. Chem. Soc. Northwest
      Region Meeting, Seattle. 1978) due to macrochelation infered from solution
      studies (S. S. Massoud, H. Sigel, Eur J. Biochem. 179, 451-458 (1989)) and
      interligand hydrogen bonding induced by metals postulated from metal-nucleotide
      structures in solid state (V. Swaminathan and M. Sundaralingam, CRC. Crit. Rev.
      Biochem. 6, 245-336 (1979)) are borne out by our structures also. The stacking
      patterns of adenine bases of both 2'-AMP.Na and 2'-AMP.K structures resemble the
      2'-AMP.NH4 structure reported in the previous article. 2'-AMP.Li, 2'-AMP.Ca and
      2'-AMP.Mg structures display base-ribose 04' stacking. An overview of interaction
      of monovalent and divalent cations with 2' and 5'-nucleotides has been presented.

PMID- 9514258
TI  - Crystal structure of glutamine phosphoribosylpyrophosphate amidotransferase from
      Escherichia coli.
AB  - Crystal structures of glutamine phosphoribosylpyrophosphate (PRPP)
      amidotransferase from Escherichia coli have been determined to 2.0-A resolution
      in the absence of ligands, and to 2.5-A resolution with the feedback inhibitor
      AMP bound to the PRPP catalytic site. Glutamine PRPP amidotransferase (GPATase)
      employs separate catalytic domains to abstract nitrogen from the amide of
      glutamine and to transfer nitrogen to the acceptor substrate PRPP. The unliganded
      and AMP-bound structures, which are essentially identical, are interpreted as the
      inhibited form of the enzyme because the two active sites are disconnected and
      the PRPP active site is solvent exposed. The structures were compared with a
      previously reported 3.0-A structure of the homologous Bacillus subtilis enzyme
      (Smith JL et al., 1994, Science 264:1427-1433). The comparison indicates a
      pattern of conservation of peptide structures involved with catalysis and
      variability in enzyme regulatory functions. Control of glutaminase activity,
      communication between the active sites, and regulation by feedback inhibitors are
      addressed differently by E. coli and B. subtilis GPATases. The E. coli enzyme is
      a prototype for the metal-free GPATases, whereas the B. subtilis enzyme
      represents the metal-containing enzymes. The structure of the E. coli enzyme
      suggests that a common ancestor of the two enzyme subfamilies may have included
      an Fe-S cluster.

PMID- 9514257
TI  - Helix capping.
AB  - Helix-capping motifs are specific patterns of hydrogen bonding and hydrophobic
      interactions found at or near the ends of helices in both proteins and peptides.
      In an alpha-helix, the first four >N-H groups and last four >C=O groups
      necessarily lack intrahelical hydrogen bonds. Instead, such groups are often
      capped by alternative hydrogen bond partners. This review enlarges our earlier
      hypothesis (Presta LG, Rose GD. 1988. Helix signals in proteins. Science 240:1632
      1641) to include hydrophobic capping. A hydrophobic interaction that straddles
      the helix terminus is always associated with hydrogen-bonded capping. From a
      global survey among proteins of known structure, seven distinct capping motifs
      are identified-three at the helix N-terminus and four at the C-terminus. The
      consensus sequence patterns of these seven motifs, together with results from
      simple molecular modeling, are used to formulate useful rules of thumb for helix
      termination. Finally, we examine the role of helix capping as a bridge linking
      the conformation of secondary structure to supersecondary structure.

PMID- 9514256
TI  - Covalent attachment of flavin adenine dinucleotide (FAD) and flavin
      mononucleotide (FMN) to enzymes: the current state of affairs.
AB  - The first identified covalent flavoprotein, a component of mammalian succinate
      dehydrogenase, was reported 42 years ago. Since that time, more than 20 covalent
      flavoenzymes have been described, each possessing one of five modes of FAD or FMN
      linkage to protein. Despite the early identification of covalent flavoproteins,
      the mechanisms of covalent bond formation and the roles of the covalent links are
      only recently being appreciated. The main focus of this review is, therefore, one
      of mechanism and function, in addition to surveying the types of linkage observed
      and the methods employed for their identification. Case studies are presented for
      a variety of covalent flavoenzymes, from which general findings are beginning to
      emerge.

PMID- 9514259
TI  - Structural features of the combining site region of Erythrina corallodendron
      lectin: role of tryptophan 135.
AB  - The role of Trp 135 and Tyr 108 in the combining site of Erythrina corallodendron
      lectin (ECorL) was investigated by physicochemical characterization of mutants
      obtained by site-directed mutagenesis, hemagglutination-inhibition studies, and
      molecular modeling, including dynamics simulations. The findings demonstrate that
      Trp 135 in ECorL: (1) is required for the tight binding of Ca2+ and Mn2+ to the
      lectin because mutation of this residue into alanine results in loss of these
      ions upon dialysis and concomitant reversible inactivation of the mutant; (2)
      contributes to the high affinity of methyl alpha-N-dansylgalactosaminide
      (MealphaGalNDns) to the lectin; and (3) is solely responsible for the
      fluorescence energy transfer between the aromatic residues of the lectin and the
      dansyl group in the ECorL-MealphaGalNDns complex. Docking of MealphaGalNDns into
      the combining site of the lectin reveals that the dansyl moiety is parallel with
      the indole of Trp 135, as required for efficient fluorescence energy transfer, in
      one of the two possible conformations that this ligand assumes in the bound
      state. In the W135A mutant, which still binds MealphaGalNDns strongly, the dansyl
      group may partially insert itself into the place formerly occupied by Trp 135, a
      process that from dynamics simulations does not appear to be energetically
      favored unless the loop containing this residue assumes an open conformation.
      However, a small fraction of the W135A molecules must be able to bind
      MealphaGalNDns in order to explain the relatively high affinity, as compared to
      galactose, still remaining for this ligand. A model for the molecular events
      leading to inactivation of the W135A mutant upon demetallization is also
      presented in which the cis-trans isomerization of the Ala 88-Asp 89 peptide bond,
      observed in high-temperature dynamics simulations, appears not to be a required
      step.

PMID- 9514260
TI  - Modular organization of inteins and C-terminal autocatalytic domains.
AB  - Analysis of the conserved sequence features of inteins (protein "introns")
      reveals that they are composed of three distinct modular domains. The N-terminal
      (N) and C-terminal (C) domains are predicted to perform different parts of the
      autocatalytic protein splicing reaction. An optional endonuclease domain (EN) is
      shown to correspond to different types of homing endonucleases in different
      inteins. The N domain contains motifs predicted to catalyze the first steps of
      protein splicing, leading to the cleavage of the intein N terminus from its
      protein host. Intein N domain motifs are also found in C-terminal autocatalytic
      domains (CADs) present in hedgehog and other protein families. Specific residues
      in the N domain of intein and CADs are proposed to form a charge relay system
      involved in cleaving their N-termini. The intein C domain is apparently unique to
      inteins and contains motifs that catalyze the final protein splicing steps:
      ligation of the intein flanks and cleavage of its C terminus to release the free
      intein and spliced host protein. All intein EN domains known thus far have
      dodecapeptide (DOD, LAGLI-DADG) type homing endonuclease motifs. This work
      identifies an EN domain with an HNH homing-endonuclease motif and two new small
      inteins with no EN domains. One of these small inteins might be inactive or a
      "pseudo intein." The results suggest a modular architecture for inteins, clarify
      their origin and relationship to other protein families, and extend recent
      experimental findings on the functional roles of intein N, C, and EN motifs.

PMID- 9514261
TI  - Protein conformer selection by ligand binding observed with crystallography.
AB  - A large-scale movement between "closed" and "open" conformations of a protein
      loop was observed directly with protein crystallography by trapping individual
      conformers through binding of an exogenous ligand and characterization with
      solution kinetics. The buried indole ring of Trp191 in cytochrome c peroxidase
      (CCP) was displaced by exogenous ligands, causing a conformational change of loop
      Pro190-Asn195 and exposing Trp191 to the protein surface. Kinetic measurements
      are consistent with a two-step binding mechanism in which the rate-limiting step
      is a transition of the protein to the open state, which then binds the ligand.
      This large-scale conformational change of a functionally important region of CCP
      is independent of ligand and indicates that about 4% of the wild-type protein is
      in the open form in solution at any given time.

PMID- 9514262
TI  - Structural analysis of the multienzyme aminoacyl-tRNA synthetase complex: a three
      domain model based on reversible chemical crosslinking.
AB  - A subset of eukaryotic aminoacyl-tRNA synthetases (a-RS) are contained in a
      multienzyme complex for which little structural detail is known. Three reversible
      chemical crosslinking reagents have been used to investigate the arrangement of
      polypeptides within this particle as isolated from rabbit reticulocytes.
      Identification of the crosslinked protein pairs was accomplished by two
      dimensional SDS diagonal gel electrophoresis. Seventeen neighboring protein pairs
      have been identified. Eight are seen with at least two reagents: K-RS:p38, D-RS:K
      RS, R-RS dimer, K-RS dimer, K-RS:Q-RS, E/P-RS:K-RS, E/P-RS:I-RS, and Q-RS with
      one of the nonsynthetase proteins. Nine more are observed with one reagent: D-RS
      dimer, R-RS:p43, D-RS:Q-RS, D-RS:M-RS, K-RS:L-RS, I-RS:R-RS, D-RS:E/P-RS, I-RS:Q
      RS, I-RS:L-RS. One trimeric association is seen: E/P-RS:I-RS:L-RS. The observed
      neighboring protein pairs suggest that the polypeptides within the aminoacyl-tRNA
      synthetase complex are distributed in three structural domains of similar mass.
      These can be arranged in a U-shaped particle in which each "arm" is considered a
      domain and the third forms the "base" of the structure. The arms have been termed
      domain I (D-RS, M-RS, Q-RS) and domain II (K-RS, R-RS), with domain III (E/P-RS,
      I-RS, L-RS) assigned to the base. The smaller proteins (p38, p43) may bridge the
      domains. This proposed spatial relationship of these domains, as well as their
      compositions, are consistent with earlier studies. Thus, this study provides an
      initial three-dimensional working model of the arrangement of polypeptides within
      the multienzyme aminoacyl-tRNA synthetase complex.

PMID- 9514263
TI  - Prime region subsite specificity characterization of human cathepsin D: the
      dominant role of position 128.
AB  - In order to contribute to our understanding of cathepsin D (CatD) active site
      specificity, two series of chromogenic octapeptides with systematic substitutions
      in positions P2' and P3' were synthesized. This panel was characterized with
      native human liver cathepsin D (nHuCatD) and yielded information concerning
      specificity trends within the S2' and S3' subsites. The pepstatin inhibited
      crystal structure of nHuCatD (Baldwin et al., 1993) was then utilized in
      conjunction with these subsite preference data to identify residues suspected of
      contributing to "prime" side subsite specificity. These residues were targeted
      for site-directed mutagenesis using the re-engineered recombinant model, "short"
      pseudocathepsin D (Beyer & Dunn, 1996). As a result of these analyses it was
      determined that prime region subsites do contribute to the unique specificity of
      human CatD. Furthermore, it was ascertained that the poly-proline loop does not
      have an active role in S3' subsite specificity. Lastly, it appears that Ile128
      has a dominant role on S2' subsite specificity whereas Val130 does not.

PMID- 9514264
TI  - Subdomain interactions as a determinant in the folding and stability of T4
      lysozyme.
AB  - The folding of large, multidomain proteins involves the hierarchical assembly of
      individual domains. It remains unclear whether the stability and folding of
      small, single-domain proteins occurs through a comparable assembly of small,
      autonomous folding units. We have investigated the relationship between two
      subdomains of the protein T4 lysozyme. Thermodynamically, T4 lysozyme behaves as
      a cooperative unit and the unfolding transition fits a two-state model. The
      structure of the protein, however, resembles a dumbbell with two potential
      subdomains: an N-terminal subdomain (residues 13-75), and a C-terminal subdomain
      (residues 76-164 and 1-12). To investigate the effect of uncoupling these two
      subdomains within the context of the native protein, we created two circular
      permutations, both at the subdomain interface (residues 13 and 75). Both variants
      adopt an active wild-type T4 lysozyme fold. The protein starting with residue 13
      is 3 kcal/mol less stable than wild type, whereas the protein beginning at
      residue 75 is 9 kcal/mol less stable, suggesting that the placement of the
      termini has a major effect on protein stability while minimally affecting the
      fold. When isolated as protein fragments, the C-terminal subdomain folds into a
      marginally stable helical structure, whereas the N-terminal subdomain is
      predominantly unfolded. ANS fluorescence studies indicate that, at low pH, the C
      terminal subdomain adopts a loosely packed acid state. An acid state intermediate
      is also seen for all of the full-length variants. We propose that this acid state
      is comprised of an unfolded N-terminal subdomain and a loosely folded C-terminal
      subdomain.

PMID- 9514266
TI  - How do potentials derived from structural databases relate to "true" potentials?
AB  - Knowledge-based potentials are used widely in protein folding and inverse folding
      algorithms. Two kinds of derivation methods are used. (1) The interactions in a
      database of known protein structures are assumed to obey a Boltzmann
      distribution. (2) The stability of the native folds relative to a manifold of
      misfolded structures is optimized. Here, a set of previously derived contact and
      secondary structure propensity potentials, taken as the "true" potentials, are
      employed to construct an artificial protein structural database from protein
      fragments. Then, new sets of potentials are derived to see how they are related
      to the true potentials. Using the Boltzmann distribution method, when the
      stability of the structures in the database lies within a certain range, both
      contact potentials and secondary structure propensities can be derived separately
      with remarkable accuracy. In general, the optimization method was found to be
      less accurate due to errors in the "excess energy" contribution. When the excess
      energy terms are kept as a constraint, the true potentials are recovered exactly.

PMID- 9514265
TI  - Archael phosphoproteins. Identification of a hexosephosphate mutase and the alpha
      subunit of succinyl-CoA synthetase in the extreme acidothermophile Sulfolobus
      solfataricus.
AB  - When soluble extracts from the extreme acidophilic archaeon Sulfolobus
      solfataricus were incubated with [gamma-32P]ATP, several radiolabeled
      polypeptides were observed following SDS-PAGE. The most prominent of these
      migrated with apparent molecular masses of 14, 18, 35, 42, 46, 50, and 79 kDa.
      Phosphoamino acid analysis revealed that all of the proteins contained
      phosphoserine, with the exception of the 35-kDa one, whose protein-phosphate
      linkage proved labile to strong acid. The observed pattern of phosphorylation was
      influenced by the identity of the divalent metal ion cofactor used, Mg2+ versus
      Mn2+, and the choice of incubation temperature. The 35- and 50-kDa
      phosphoproteins were purified and their amino-terminal sequences determined. The
      former polypeptide's amino-terminal sequence closely matched a conserved portion
      of the alpha-subunit of succinyl-CoA synthetase, which forms an acid-labile
      phosphohistidyl enzyme intermediate during its catalytic cycle. This
      identification was confirmed by the ability of succinate or ADP to specifically
      remove the radiolabel. The 50-kDa polypeptide's sequence contained a heptapeptide
      motif, Phe/Pro-Gly-Thr-Asp/Ser-Gly-Val/Leu-Arg, found in a similar position in
      several hexosephosphate mutases. The catalytic mechanism of these mutases
      involves formation of a phosphoseryl enzyme intermediate. The identity of p50 as
      a hexosephosphate mutase was confirmed by (1) the ability of sugars and sugar
      phosphates to induce removal of the labeled phosphoryl group from the protein,
      and (2) the ability of [32P]glucose 6-phosphate to donate its phosphoryl group to
      the protein.

PMID- 9514267
TI  - Folded conformations of antigenic peptides from riboflavin carrier protein in
      aqueous hexafluoroacetone.
AB  - Riboflavin carrier protein (RCP) plays an important role in transporting vitamin
      B2 across placental membranes, a process critical for maintenance of pregnancy.
      Association of the vitamin with the carrier protein ensures optimal
      bioavailability, facilitating transport. The conformations of three antigenic
      peptide fragments encompassing residues 4-23 (N21), 170-186 (R18), and 200-219
      (Y21) from RCP, which have earlier been studied as potential leads toward a
      synthetic peptide-based contraceptive vaccine, have been investigated using CD
      and NMR spectroscopy in aqueous solution and in the presence of the structure
      stabilizing cosolvent hexafluoroacetone trihydrate (HFA). In aqueous solution at
      pH 3.0, all three peptides are largely unstructured, with limited helical
      population for the peptides R18 and Y21. The percentage of helicity estimated
      from CD experiments is 10% for both the peptides. A dramatic structural
      transition from an unstructured state to a helical state is achieved with
      addition of HFA, as evidenced by intensification of CD bands at 222 nm and 208 nm
      for Y21 and R18. The structural transition is completed at 50% HFA (v/v) with 40%
      and 35% helicity for R18 and Y21, respectively. No structural change is evident
      for the peptide N21, even in the presence of HFA. NMR analysis of the three
      peptides in 50% HFA confirms a helical conformation of R18 and Y21, as is evident
      from upfield shifts of CalphaH resonances and the presence of many sequential
      NH/NH NOEs with many medium-range NOEs. The helical conformation is well
      established at the center of the sequence, with substantial fraying at the
      termini for both the peptides. An extended conformation is suggested for the N21
      peptide from NMR studies. The helical region of both the peptides (R18, Y21)
      comprises the core epitopic sequence recognized by the respective monoclonal
      antibodies. These results shed some light on the issue of structure and folding
      of antigenic peptides.

PMID- 9514269
TI  - Protein fold recognition without Boltzmann statistics or explicit physical basis.
AB  - We present a fast method for finding optimal parameters for a low-resolution
      (threading) force field intended to distinguish correct from incorrect folds for
      a given protein sequence. In contrast to other methods, the parameterization uses
      information from >10(7) misfolded structures as well as a set of native sequence
      structure pairs. In addition to testing the resulting force field's performance
      on the protein sequence threading problem, results are shown that characterize
      the number of parameters necessary for effective structure recognition.

PMID- 9514268
TI  - NMR studies of internal dynamics of serine proteinase protein inhibitors: Binding
      region mobilities of intact and reactive-site hydrolyzed Cucurbita maxima trypsin
      inhibitor (CMTI)-III of the squash family and comparison with those of
      counterparts of CMTI-V of the potato I family.
AB  - Serine proteinase protein inhibitors follow the standard mechanism of inhibition
      (Laskowski M Jr, Kato I, 1980, Annu Rev Biochem 49:593-626), whereby an enzyme
      catalyzed equilibrium between intact (I) and reactive-site hydrolyzed inhibitor
      (I*) is reached. The hydrolysis constant, Khyd, is defined as [I*]/[I]. Here, we
      explore the role of internal dynamics in the resynthesis of the scissile bond by
      comparing the internal mobility data of intact and cleaved inhibitors belonging
      to two different families. The inhibitors studied are recombinant Cucurbita
      maxima trypsin inhibitor III (rCMTI-III; Mr 3 kDa) of the squash family and rCMTI
      V (Mr approximately 7 kDa) of the potato I family. These two inhibitors have
      different binding loop-scaffold interactions and different Khyd values--2.4 (CMTI
      III) and 9 (CMTI-V)--at 25 degrees C. The reactive-site peptide bond (P1-P1') is
      that between Arg5 and Ile6 in CMTI-III, and that between Lys44 and Asp45 in CMTI
      V. The order parameters (S2) of backbone NHs of uniformly 15N-labeled rCMTI-III
      and rCMTI-III* were determined from measurements of 15N spin-lattice and spin
      spin relaxation rates, and [1H]-15N steady-state heteronuclear Overhauser
      effects, using the model-free formalism, and compared with the data reported
      previously for rCMTI-V and rCMTI-V*. The backbones of rCMTI-III [(S2) = 0.71] and
      rCMTI-III* [(S2) = 0.63] are more flexible than those of rCMTI-V [(S2) = 0.83]
      and rCMTI-V* [(S2) = 0.85]. The binding loop residues, P4-P1, in the two proteins
      show the following average order parameters: 0.57 (rCMTI-III) and 0.44 (rCMTI
      III*); 0.70 (rCMTI-V) and 0.40 (rCMTI-V*). The P1'-P4' residues, on the other
      hand, are associated with (S2) values of 0.56 (rCMTI-III) and 0.47 (rCMTI-III*);
      and 0.73 (rCMTI-V) and 0.83 (rCMTI-V*). The newly formed C-terminal (Pn residues)
      gains a smaller magnitude of flexibility in rCMTI-III* due to the Cys3-Cys20
      crosslink. In contrast, the newly formed N-terminal (Pn' residues) becomes more
      flexible only in rCMTI-III*, most likely due to lack of an interaction between
      the P1' residue and the scaffold in rCMTI-III. Thus, diminished flexibility gain
      of the Pn residues and, surprisingly, increased flexibility of the Pn' residues
      seem to facilitate the resynthesis of the P1-P1' bond, leading to a lower Khyd
      value.

PMID- 9514270
TI  - Mapping fatty acid binding to beta-lactoglobulin: Ligand binding is restricted by
      modification of Cys 121.
AB  - Native beta-lactoglobulin (Blg) binds 1 mole of palmitic acid per mole of protein
      with a dissociation constant of 0.6 microM for the primary fatty acid binding
      site. Chemical modification of Cys 121, which lies at the external putative
      hydrophobic binding site of Blg, does not affect retinol or 4,4'-bis 1
      (phenylamino)-8-naphthalenesulfonate (bis-ANS) binding to the protein, indicating
      that the incorporated appendages do not perturb the internal hydrophobic site
      within the beta-barrel of Blg (i.e., the retinoid site is unaffected). On the
      other hand, methylation of Cys 121, reduces the affinity of Blg for palmitic acid
      by 10-fold as monitored by intrinsic fluorescence. Modification of the Cys 121
      with methylmethanethiosulfonate or a thiol-specific spin label appears to either
      further weaken or totally eliminate fatty acid binding, respectively, due to
      steric hindrance. Furthermore, this binding pattern has been independently
      verified using a spin labeled fatty acid analog and monitoring ESR as well as by
      bis-ANS fluorescence when bound to the protein. These results suggest that fatty
      acids bind at the "external site" of beta-lactoglobulin, between the sole alpha
      helix and the beta-barrel. In addition, structural stability studies of native
      and chemically modified Blg appear to confirm this observation as well.

PMID- 9514271
TI  - The response of T4 lysozyme to large-to-small substitutions within the core and
      its relation to the hydrophobic effect.
AB  - To further examine the structural and thermodynamic basis of hydrophobic
      stabilization in proteins, all of the bulky non-polar residues that are buried or
      largely buried within the core of T4 lysozyme were substituted with alanine. In
      25 cases, including eight reported previously, it was possible to determine the
      crystal structures of the variants. The structures of four variants with double
      substitutions were also determined. In the majority of cases the "large-to-small"
      substitutions lead to internal cavities. In other cases declivities or channels
      open to the surface were formed. In some cases the structural changes were
      minimal (mainchain shifts < or = 0.3 A); in other cases mainchain atoms moved up
      to 2 A. In the case of Ile 29 --> Ala the structure collapsed to such a degree
      that the volume of the putative cavity was zero. Crystallographic analysis
      suggests that the occupancy of the engineered cavities by solvent is usually low.
      The mutants Val 149 --> Ala (V149A) and Met 6 --> Ala (M6A), however, are
      exceptions and have, respectively, one and two well-ordered water molecules
      within the cavity. The Val 149 --> Ala substitution allows the solvent molecule
      to hydrogen bond to polar atoms that are occluded in the wild-type molecule.
      Similarly, the replacement of Met 6 with alanine allows the two solvent molecules
      to hydrogen bond to each other and to polar atoms on the protein. Except for Val
      149 --> Ala the loss of stability of all the cavity mutants can be rationalized
      as a combination of two terms. The first is a constant for a given class of
      substitution (e.g., -2.1 kcal/mol for all Leu --> Ala substitutions) and can be
      considered as the difference between the free energy of transfer of leucine and
      alanine from solvent to the core of the protein. The second term can be
      considered as the energy cost of forming the cavity and is consistent with a
      numerical value of 22 cal mol(-1) A(-3). Physically, this term is due to the loss
      of van der Waal's interactions between the bulky sidechain that is removed and
      the atoms that form the wall of the cavity. The overall results are consistent
      with the prior rationalization of Leu --> Ala mutants in T4 lysozyme by Eriksson
      et al. (Eriksson et al., 1992, Science 255:178-183).

PMID- 9514272
TI  - Purification and characterization of the heteromeric transcriptional activator
      MvaT of the Pseudomonas mevalonii mvaAB operon.
AB  - The mvaAB operon of Pseudomonas mevalonii encodes HMG-CoA reductase (EC 1.1.1.88)
      and HMG-CoA lyase (EC 4.1.3.4), enzymes that catalyze the initial reactions of
      mevalonate catabolism in this organism. Expression of this operon is regulated by
      the constitutively expressed transcriptional activator protein MvaT that binds in
      vitro to an upstream regulatory element. Mevalonate is essential for activation
      of transcription in vivo, and in vitro data demonstrated that MvaT binds to the
      mvaAB cis-regulatory element in the absence of mevalonate with a Kd,app of 2 nM.
      Purification of MvaT enriched for two polypeptides of approximate molecular mass
      15 kDa and 16 kDa, designated P15 and P16. MvaT, assayed by its DNA-binding
      activity, comigrated with P15 and P16 during DNA-affinity chromatography, size
      exclusion chromatography, and sucrose density gradient centrifugation. P15 and
      P16 also comigrated during denaturing isoelectric focusing of purified MvaT.
      Treatment of MvaT with dimethylsuberimidate formed a 31-kDa polypeptide complex
      that contained N-terminal sequences from P15 and P16. The apparent association of
      P15 and P16 in solution and their copurification with MvaT activity strongly
      suggests that MvaT is comprised of these two subunits. Size-exclusion
      chromatography gave an estimated molecular mass for MvaT of 33 kDa. A partial DNA
      sequence of the P16 gene was obtained using PCR employing degenerate primers
      directed against the N-termini of P15 and P16. P16 appears to be comprised of at
      least 128 aminoacyl residues having a predicted molecular mass of 14.3 kDa.

PMID- 9514273
TI  - Contaminant inclusion into protein crystals analyzed by electrospray mass
      spectrometry and X-ray crystallography.
AB  - The inclusion of protein contaminants into crystals of turkey egg white lysozyme
      (TEWL) was investigated by electrospray mass spectrometry of the dissolved
      crystals. The results show that significant amounts of the structurally related
      contaminant hen egg white lysozyme (HEWL) are included in the crystals of TEWL.
      The structurally unrelated contaminant RNAse A, on the other hand, is not
      included. The X-ray diffraction data statistics of a hybrid TEWL/HEWL crystal and
      an uncontaminated TEWL crystal were of similar quality. This indicates that, even
      though the crystals contain much higher levels of the contaminant than one would
      have expected after a recrystallization experiment, they are still suitable for X
      ray diffraction experiments. However, attempts to detect the presence of the
      contaminant in the crystal by crystallographic structure refinement did not yield
      conclusive results.

PMID- 9514274
TI  - Conformation, stability, and active-site cysteine titrations of Escherichia coli
      D26A thioredoxin probed by Raman spectroscopy.
AB  - The active-site cysteines (Cys 32 and Cys 35) of Escherichia coli thioredoxin are
      oxidized to a disulfide bridge when the protein mediates substrate reduction. In
      reduced thioredoxin, Cys 32 and Cys 35 are characterized by abnormally low pKa
      values. A conserved side chain, Asp 26, which is sterically accessible to the
      active site, is also essential to oxidoreductase activity. pKa values governing
      cysteine thiol-thiolate equilibria in the mutant thioredoxin, D26A, have been
      determined by direct Raman spectrophotometric measurement of sulfhydryl
      ionizations. The results indicate that, in D26A thioredoxin, both sulfhydryls
      titrate with apparent pKa values of 7.5+/-0.2, close to values measured
      previously for wild-type thioredoxin. Sulfhydryl Raman markers of D26A and wild
      type thioredoxin also exhibit similar band shapes, consistent with minimal
      differences in respective cysteine side-chain conformations and sulfhydryl
      interactions. The results imply that neither the Cys 32 nor Cys 35 SH donor is
      hydrogen bonded directly to Asp 26 in the wild-type protein. Additionally, the
      thioredoxin main-chain conformation is largely conserved with D26A mutation.
      Conversely, the mutation perturbs Raman bands diagnostic of tryptophan (Trp 28
      and Trp 31) orientations and leads to differences in their pH dependencies,
      implying local conformational differences near the active site. We conclude that,
      although the carboxyl side chain of Asp 26 neither interacts directly with active
      site cysteines nor is responsible for their abnormally low pKa values, the
      aspartate side chain may play a role in determining the conformation of the
      enzyme active site.

PMID- 9514275
TI  - How many membrane proteins are there?
AB  - One of the basic issues that arises in functional genomics is the ability to
      predict the subcellular location of proteins that are deduced from gene and
      genome sequencing. In particular, one would like to be able to readily specify
      those proteins that are soluble and those that are inserted in a membrane.
      Traditional methods of distinguishing between these two locations have relied on
      extensive, time-consuming biochemical studies. The alternative approach has been
      to make inferences based on a visual search of the amino acid sequences of
      presumed gene products for stretches of hydrophobic amino acids. This numerical,
      sequence-based approach is usually seen as a first approximation pending more
      reliable biochemical data. The recent availability of large and complete sequence
      data sets for several organisms allows us to determine just how accurate such a
      numerical approach could be, and to attempt to minimize and quantify the error
      involved. We have optimized a statistical approach to protein location
      determination. Using our approach, we have determined that surprisingly few
      proteins are misallocated using the numerical method. We also examine the
      biological implications of the success of this technique.

PMID- 9514276
TI  - Computation of electrostatic complements to proteins: a case of charge stabilized
      binding.
AB  - Recent evidence suggests that the net effect of electrostatics is generally to
      destabilize protein binding due to large desolvation penalties. A novel method
      for computing ligand-charge distributions that optimize the tradeoff between
      ligand desolvation penalty and favorable interactions with a binding site has
      been applied to a model for barnase. The result is a ligand-charge distribution
      with a favorable electrostatic contribution to binding due, in part, to ligand
      point charges whose direct interaction with the binding site is unfavorable, but
      which make strong intra-molecular interactions that are uncloaked on binding and
      thus act to lessen the ligand desolvation penalty.

PMID- 9514277
TI  - Cloning, overexpression, purification, and spectroscopic characterization of
      human S100P.
AB  - The calcium-binding protein S100P has been found to be associated with human
      prostate cancer. We have overexpressed S100P in Escherichia coli using a T7
      expression system. A rapid two-step procedure for the isolation of overexpressed
      S100P leads to a preparation of >95% pure protein with a yield of approximately
      150 mg per liter of culture. The structural integrity of recombinant S100P was
      analyzed using CD and fluorescence spectroscopic techniques. The far-UV CD shows
      that secondary structure of recombinant S100P consists predominantly of a-helical
      structure. Both near-UV CD and tyrosine fluorescence spectra show that aromatic
      residues are involved in the formation of a specific, well packed structure,
      indicating that the recombinant S100P protein adopts a compact folded
      conformation. Ca2+ has a profound effect on S100P structure. Near-UV CD and
      fluorescence intensity of both internal (tyrosine) and external (ANS) probes
      suggest significant structural rearrangements in the tertiary structure of the
      molecule. The similarity of far-UV CD spectrum of S100P in the presence and in
      the absence of Ca2+ suggests that Ca2+ binding has only minor effects on
      secondary structure.

PMID- 9514278
TI  - Fragment of GABA(A) receptor containing key ligand-binding residues overexpressed
      in Escherichia coli.
AB  - GABA(A) receptor plays a major role in inhibitory synaptic transmission in the
      central nervous system and is the target of drugs such as the benzodiazepine
      tranquilizers. The polymeric membrane protein nature of GABA(A) receptor has
      rendered structural elucidation of the receptor a formidable task, greatly
      hampering structure-based drug design. We report here the first expression in
      Escherichia coli of a fragment of GABA(A) receptor. This 131-residue fragment,
      spanning Cys166 to Leu296 of human GABAA receptor alpha1 subunit, contains
      residues previously suggested to be involved in benzodiazepine binding. The
      overexpressed non-fusion recombinant protein was purified to near homogeneity and
      characterized by circular dichroism (CD), which showed that the recombinant
      protein has well defined secondary structures where beta-strands are dominant.
      The stability of the secondary structures was demonstrated by CD spectra at high
      pH and elevated temperature. Excluding part of the sequences from the carboxyl
      terminal of the fragment resulted in dramatic changes in the secondary structures
      comparable to the effects caused by SDS denaturation. Our results therefore
      suggest that the 131-residue fragment harbors an integral structural domain of
      the receptor. The overexpression of the recombinant protein fragment thus opens
      the way to the biochemical and structural studies of a functionally important
      region of the receptor, and exemplifies an effective approach of expression and
      characterization that potentially may be extended to other members of the ligand
      gated channel receptor superfamily, to which the GABA(A) receptor belongs.

PMID- 9514279
TI  - From lipoic acid to multi-enzyme complexes.

PMID- 9514280
TI  - Neurocircuitry targets in ethanol reward and dependence.
AB  - Alcoholism is a complex behavioral disorder characterized by excessive
      consumption of ethanol, a narrowing of the behavioral repertoire toward excessive
      consumption, the development of tolerance and dependence, and impairment in
      social and occupational functioning. Animal models of the complete syndrome of
      alcoholism are difficult if not impossible to achieve, but validated animal
      models exist for many of the different components of the syndrome. Recent work
      has begun to define the neurocircuits responsible for the two major sources of
      reinforcement key to animal models of excessive ethanol intake: positive and
      negative reinforcement. Ethanol appears to interact with ethanol-sensitive
      elements within neuronal membranes that convey the specificity of neurochemical
      action. Ethanol reinforcement appears to be mediated by an activation of GABA-A
      receptors, release of opioid peptides, release of dopamine, inhibition of
      glutamate receptors, and interaction with serotonin systems. These neurocircuits
      may be altered by chronic ethanol administration as reflected by opposite effects
      during acute ethanol withdrawal and by the recruitment of other neurotransmitter
      systems such as the stress neuropeptide corticotropin-releasing factor. Future
      challenges will include a focus on understanding how these neuroadaptive changes
      convey vulnerability to relapse in animals with a history of ethanol dependence.

PMID- 9514281
TI  - Ethanol action on neural networks studied with multineuron recording in freely
      moving animals.
AB  - The advent of new chronic multineuron recording techniques for examining neural
      activity in behaving animals has initiated a new phase in the analysis of the
      neuronal mechanisms that underlie ethanol and other drug self-administration. The
      technique allows for the simultaneous recording of groups of individual neurons
      in one or more brain regions during ongoing behavior; therefore, the spatio
      temporal patterns of neuronal activity during specific behavioral events can be
      determined. We have successfully applied this technique to rat models of cocaine
      and heroin self-administration. Recently, using rats, we have been able to record
      from neurons in areas of the mesocorticolimbic circuit during ethanol-reinforced
      operant responding. In this review, we describe the current and future
      application of this new behavioral neurophysiology to the investigation of the
      neurobiology of alcohol addiction.

PMID- 9514282
TI  - Cognitive correlates of single neuron activity in task-performing animals:
      application to ethanol research.
AB  - The deleterious effects of ethanol on cognitive processes result from an
      interaction between ethanol and the neural structures that are critical for
      executing those cognitive functions. Results from studies that employ
      contemporary behavioral neuroscience techniques are beginning to elucidate the
      neural circuits that underlie specific cognitive processes, and the stage is set
      for rigorous investigations into the neural basis for ethanol-induced cognitive
      impairments. In this article, the application of single neuron recording
      techniques to the study of the memory and attentional deficits produced by acute
      exposure to low levels of ethanol are described, with an emphasis on the
      advantages of combining physiological techniques with operant behavioral
      procedures in rats. After reviewing background information on the basic
      neurophysiological and behavioral techniques, empirical results from this
      laboratory will be used to illustrate how single-unit analysis can be applied to
      the study of ethanol-induced cognitive impairments.

PMID- 9514283
TI  - Real-time assessments of dopamine function during behavior: single-unit
      recording, iontophoresis, and fast-scan cyclic voltammetry in awake, unrestrained
      rats.
AB  - Although ample evidence implicates the dopamine (DA) projection to the
      neostriatum and nucleus accumbens in motor and motivational processes, relatively
      little information is available on how DA alters neostriatal or accumbal
      functions under naturally occurring behavioral conditions. Further insight into
      neuron-behavior relationships can be achieved with the application of single-unit
      recording techniques, including iontophoresis and fast-scan cyclic voltammetry
      (FSCV), to awake, unrestrained animals. Single-unit recording has revealed that
      amphetamine, a widely abused psychomotor stimulant, activates motor-, but
      inhibits nonmotor-related neurons in neostriatum and nucleus accumbens. Although
      either response can be blocked by DA receptor antagonists, the amphetamine
      induced activation also depends on an intact corticostriatal system, suggesting a
      role for glutamate (GLU). Both neostriatal and accumbal neurons are sensitive to
      iontophoretic application of either DA or GLU, but when applied during low-dose
      application of DA, the GLU signal is enhanced relative to background activity. In
      effect, DA appears to modulate GLU by strengthening the GLU signal-to-noise
      ratio. To assess DA release under behaviorally relevant conditions, FSCV has been
      used to obtain real-time measurements of DA efflux in a free-choice novelty test.
      DA efflux increased only during the brief period of entry into novelty, and the
      increase was confined to accumbal shell and the shell-core transition zone, the
      so-called shore. Neither accumbal core nor the overlying neostriatum showed a
      novelty-related DA change. Thus, DA release during behavior is not uniform and in
      the case of novelty appears targeted to the limbic-related area of accumbal
      shell. Further application of these and other in vivo technologies to ambulant
      animals is required to identify the complex mechanisms underlying both the
      release of DA and its effect on neostriatal and accumbal neurons during behavior.

PMID- 9514284
TI  - Application of the combined single-cell recording/intracerebral microdialysis
      method to alcohol research in freely behaving animals.
AB  - Intercellular communication in brain is coded in neuronal firing patterns,
      determined by the interplay of intra- and extracellular molecular systems. It is
      not clear how ethanol perturbs this molecular interplay in the motivational,
      emotional, and cognitive neural networks in brain to induce those specific,
      aberrant, cell-firing patterns that lead to craving for alcohol, excessive
      alcohol consumption, and impaired cognition. However, resolution of this problem
      is essential to an understanding of the basic mechanisms of alcohol-related
      disorders and to develop effective therapies for their treatment. It is difficult
      to obtain information on the molecular background of cell-firing regulation in
      brain during behavioral events. We have recently developed a new in vivo method,
      combined single-cell recording/intracerebral microdialysis in freely behaving
      animals, which has the ability to extract such information from brain. The
      principal feature of the technique is that it records the firing of single
      neurons in discrete brain sites and deliver drugs, alone or in combinations, via
      microdialysis, into the extracellular environment of the recorded cells, while
      the experimental animal is behaving freely. Accordingly, the method allows the
      determination of drug actions on cellular firing within distinct neural circuits
      during normal and abnormal behaviors. Thus, it can provide insights into the
      physiological or pathophysiological molecular machinery of the examined cells.
      The present paper describes this method, demonstrates how administration of
      ethanol via intrahippocampal microdialysis affects the firing of hippocampal
      place cells, and discusses the potential of the technique in future alcohol
      research.

PMID- 9514285
TI  - Organotypic brain slice cultures for functional analysis of alcohol-related
      disorders: novel versus conventional preparations.
AB  - Assessment of long-term alterations in neural function and phenotype has usually
      involved culture techniques that utilize dissociated preparations. Recently, we
      have approached such topics in alcohol research by using brain slice cultures,
      also known as explant or organotypic preparations. In this symposium
      presentation, two preparations will be discussed, and examples of the particular
      advantages of these preparations will be presented in relation to alcohol
      research. First, we use the hippocampal explant preparation for assessment of
      long-term alterations in N-methyl-D-aspartate receptor (NMDAR) function due to
      chronic ethanol exposure and subsequent withdrawal. This preparation displays
      many synaptic, structural, and enzymatic phenotypes indicative of normal neural
      preparations. Patch clamp recordings reveal NMDAR-mediated excitatory
      postsynaptic current (EPSC) elicited upon stimulation of Schaffer collateral
      fibers and recorded from CA1 pyramidal cells. Long-term ethanol exposure followed
      by subsequent withdrawal resulted in a specific enhancement of NMDAR-mediated
      synaptic responses which preceded the expression of epileptiform events that
      occurred after prolonged withdrawal periods. Second, we describe a novel explant
      preparation, derived from horizontal slices of the entire forebrain and midbrain
      of the rat. These long-term explants displayed multiple normal phenotypes
      including Nissl, AChE, TH, and GFAP staining. Electrophysiologically, these
      explants displayed a functional corticostriatal pathway recorded with field and
      patch clamp techniques and elicited by synaptic stimulation. Taken together,
      these explant preparations display utility for long-term study of ethanol effects
      on neural systems, especially relating to withdrawal hyperexcitability as well as
      systems involved in drug-seeking behavior.

PMID- 9514286
TI  - Optical monitoring of living brain tissue.
AB  - Optical methods can usefully augment classical techniques such as electrical
      recording for investigating cellular and network physiology. Here, recent
      developments in optical methods--including confocal and nonlinear fluorescence
      imaging, semiconductor array imaging, and improved fluorescent indicators of ion
      concentration and transmembrane electrical potential--are briefly reviewed, and
      examples are offered that may suggest potential applications to experimental
      studies in alcoholism research.

PMID- 9514287
TI  - Research on tolerance: what can we learn from history?
AB  - The concept of tolerance to ethanol has evolved gradually over the past two
      centuries, and all of the basic clinical features, as they are now understood,
      have been clearly recognized for nearly 100 years. The basic mechanisms involved
      in central nervous system tolerance, however, have been elucidated only in the
      past 20 to 30 years. Little progress was made as long as tolerance was viewed as
      a purely cellular or physiological adaptation to alcohol, and researchers used
      overly simple paradigms based on mere exposure to the drug. With the recognition
      that learning, both operant and associative, can play a major role in the
      development of tolerance to alcohol and cross-tolerance to other drugs, a radical
      change in research approaches became possible. Most of the neural mechanisms
      related to learning and memory are now known to be involved in the development
      and retention of tolerance, and the simplistic models used in earlier research
      must now be abandoned. Nevertheless, a review of the history of past research
      points to a number of important lessons for future work, including the following:
      (1) many of the present concepts were enunciated by astute observers many decades
      ago, and research was hindered because this older literature was forgotten; (2)
      for many decades progress was slow because of a narrow focus on specific
      techniques, questions, and hypotheses that overlooked important research in
      related disciplines; (3) the course of research is often irregular, and past
      questions may have to be revisited with new approaches--but these are more likely
      to be fruitful if based on knowledge of past history; and (4) excellent
      researchers often obtain apparently contradictory findings, but the disagreements
      may hold the key to deeper understanding of the phenomena, and should not be
      brushed over by ignoring the minority findings and interpretations. As in all
      scientific research, the most important requirement for major progress is the
      formulation of good questions or hypotheses: the results yielded by the best
      available techniques can be only as good as the questions they are meant to
      answer.

PMID- 9514288
TI  - Axis I and axis II comorbidity in alcohol dependence and the two types of
      alcoholism.
AB  - BACKGROUND: Although high prevalence rates of psychiatric comorbidity were
      reported in alcoholism, there is a lack of studies covering the whole spectrum of
      DSM Axes I and II disorders. The relation of comorbid psychopathology and
      Cloninger's and Babor's types of alcoholism still remained unclear. METHODS:
      Psychiatric comorbidity in 250 hospitalized alcohol-dependent patients without
      additional substance-related disorders was assessed by the Composite
      International Diagnostic Interview and the International Personality Disorder
      Examination. Information about the course and severity of alcoholism was obtained
      from several sources. RESULTS: Additional Axis I disorders only were found in
      24.0%, Axis II disorders only in 16.4%, and concurrent Axis I and Axis II
      disorders in 17.2% (total comorbidity rate: 57.6%). Two clusters of alcohol
      dependence were found that substantially overlap with Cloninger's and Babor's
      types of alcoholism. The majority of type A subjects were found to be either not
      comorbid at all, or to be Axis I comorbid only. Type B, on the other hand, was
      preferably associated with personality disorders (mainly Clusters A and B) and
      dimensional scores of personality pathology (schizoid, schizotypal, all Cluster
      B, and passive-aggressive). CONCLUSIONS: The entire spectrum of personality
      pathology should be assessed in the comorbidity research of alcoholism. The two
      types of alcoholism differ on a variety of alcohol-related and comorbid
      personality characteristics, but further research is needed to clarify the
      underlying psychological and biological associations.

PMID- 9514289
TI  - Visual and auditory event-related potentials in young children of alcoholics from
      high- and low-density families.
AB  - Event-related potentials (ERPs), particularly the P3 wave, have been proposed as
      biological markers of genetic risk for alcoholism. The present study assesses the
      ERPs from 102 boys and girls (7 to 15 years old) divided into three groups: two
      groups of sons and daughters of alcoholic fathers, with and without other first-
      or second-degree relatives affected, and a control group of children of
      nonalcoholics. Both visual and auditory discrimination tasks with three stimuli
      (standard, target, and infrequent nontarget) were used. P3 amplitudes did not
      reach significant reduction for the high-risk males and were complex for females.
      There were significant differences among females in P3 visual latency elicited by
      targets; delays in this variable were associated with multigenerational familial
      alcoholism. Results are discussed in light of the tasks used for eliciting the
      ERPs and the characteristics of the selected sample.

PMID- 9514290
TI  - Effects of monensin on ethanol-induced alterations in function of hepatocellular
      asialoglycoprotein receptor subpopulations.
AB  - Chronic ethanol consumption is associated with multiple impairments in receptor
      mediated endocytosis (RME) in hepatocytes. RME mediated by the asialoglycoprotein
      receptor seems to be especially impaired by ethanol. In the present study, we
      determined susceptibility of RME to alterations in ethanol-fed and pair-fed
      control animals by the addition of a carboxylic ionophore, monensin. Monensin
      inhibits acidification of prelysosomal vesicular compartments, which results in a
      decrease in the rate of receptor-ligand dissociation within the cell. Low levels
      (25 microM) of monensin have been shown to preferentially affect receptor-ligand
      dissociation of one subset (state 2) of asialoglycoprotein receptor, whereas
      dissociation in a second subset (state 1 receptors) seems to be relatively
      unaffected. We examined whether ethanol treatment preferentially affected one or
      another of these receptor subpopulations. Male Wistar rats were fed a standard
      ethanol-containing (36% of calories) or control diet for 10 to 14 weeks, and
      hepatocytes were prepared from the animals. Similar to previous results from our
      laboratory, surface and total ligand and antibody binding were decreased by 30 to
      45% (p < 0.01) in ethanol animals, compared with controls. An ethanol-induced
      impairment of receptor-ligand dissociation was also apparent in these cells, as
      shown by increased ratios of bound-to-free ligand during continuous endocytosis.
      After monensin treatment, surface receptors on both ethanol and control cells
      showed a similar pattern of redistribution to the cell interior and intracellular
      inactivation. When kinetics of intracellular receptor-ligand dissociation were
      examined upon addition of monensin, the bound-to-free ligand ratios in both
      control and ethanol cells increased dramatically and to an equal extent. These
      results indicate that, in the ethanol animals, the pattern of sensitivity to
      monensin is unchanged relative to controls. Thus, the relative proportion of
      state 1 and state 2 receptor populations do not seem to be affected after long
      term feeding, and ethanol may be a perturbant that affects both state 1 and state
      2 receptor function.

PMID- 9514291
TI  - The significance of family history status in relation to neuropsychological test
      performance and cerebral glucose metabolism studied with positron emission
      tomography in older alcoholic patients.
AB  - Patients with severe chronic alcoholism have decreased rates of glucose
      metabolism in the medial frontal lobe and correlated abnormalities of
      neuropsychological functioning. The potential influence of family history of
      alcoholism has not been examined in these patients. In a retrospective study, we
      used neuropsychological tests and neuroimaging employing [18F]fluorodeoxyglucose
      with positron emission tomography to study 48 older subjects who had histories of
      severe, chronic alcohol dependence. These patients were divided into two groups:
      27 with a first-degree relative with chronic alcoholism and 21 patients without
      first-degree relative with chronic alcoholism. No differences were found between
      groups on either neuropsychological or neuroimaging tests. These results suggest
      that a family history of alcoholism does not moderate the damaging effects of
      severe chronic alcoholism on the functioning of the medial frontal lobe.

PMID- 9514292
TI  - Monitoring relapse drinking during disulfiram therapy by assay of urinary 5
      hydroxytryptophol.
AB  - Screening for recent alcohol use by testing urine for the ratio of 5
      hydroxytryptophol (5HTOL) to 5-hydroxyindole-3-acetic acid (5HIAA) was performed
      in 10 methadone patients on disulfiram (Antabuse) maintenance therapy in an
      outpatient setting. Apart from alcohol ingestion, treatment with aldehyde
      dehydrogenase inhibitors such as disulfiram is the only known cause of an
      abnormally high 5HTOL/5HIAA ratio. After introduction of drug therapy, increased
      ratios were observed in all patients. The new higher level reached was relatively
      stable over time within the same patient but variable between patients. Four
      patients continued to consume alcohol, as evidenced by 5HTOL/5HIAA ratios well
      above the new individual plateau, while still taking 400 mg disulfiram 3 times
      per week under strict supervision. To try to achieve sobriety in two patients who
      drank frequently while on therapy, the disulfiram dose was doubled. Continued
      testing demonstrated this to increase the 5HTOL/5HIAA steady-state level further,
      and the absence of extreme values above this new baseline level indicated
      adherence to abstinence with possibly one single relapse. When disulfiram
      administration was discontinued, as planned, by five of the patients, four of
      them returned to drinking very soon. The present results show that during
      disulfiram maintenance the continuous inhibition of aldehyde dehydrogenase
      produces a new higher and dose-related 5HTOL to 5HIAA steady state level in
      urine, but relapse to drinking will still lead to further increased 5HTOL/5HIAA
      ratios. It is also suggested that an individual dose-titration regimen, whereby
      the disulfiram dose is raised gradually until 5HTOL/5HIAA testing indicates
      sobriety, will improve therapeutic effectiveness.

PMID- 9514293
TI  - Relevance of both daily hassles and the ALDH2 genotype to problem drinking among
      Japanese male workers.
AB  - The effects of genetic polymorphisms in the ALDH2 and ADH2 genes and stress
      levels, as assessed by the daily hassles scale on the prevalence of problem
      drinkers, were investigated in males in a Japanese occupational population. The
      frequency of problem drinkers was estimated by the Kurihama Alcoholism Screening
      Test (KAST). The prevalence of those with a high KAST score (> or =0.0) was
      significantly higher in ALDH2*1/*1 (18.4%) than in ALDH2*1/*2 (4.8%). Multiple
      logistic regression analysis revealed significant contributions by levels of
      alcohol consumption, the ALDH2 genotype, and daily hassles to the prevalence of
      those with a high KAST score. When we analyzed the data for each ALDH2 genotype,
      heavier alcohol consumption (> or =28.8 ml/day), older age (> or =40 years old),
      and very high daily hassles levels (> or =20) significantly increased the
      prevalence of problem drinkers in ALDH2*1/*1. On the contrary, no variables other
      than heavier alcohol consumption influenced the prevalence in ALDH2*1/*2. In
      summary, the present study revealed significant contributions of both daily
      hassles and the ALDH2 genotype to the increase of problem drinkers in an
      occupational population. Health promotion activities to prevent from alcohol
      dependence should focus on ALDH2*1/*1, especially those of middle age, and should
      include stress management as a part of their activities.

PMID- 9514294
TI  - Alcohol and drug CAGE screeners for pregnant, low-income women: the California
      Perinatal Needs Assessment.
AB  - The purpose of this study is to evaluate a revised CAGE and a new drug version of
      the CAGE as screeners for risk of heavier or problem alcohol and/or drug use
      among a population of low-income, pregnant women and adolescents (n = 1147)
      recruited from 19 agencies in two California counties. Two versions of the CAGE
      were used in this analysis: (1) the 4-item Alcohol CAGE, using the year before
      knowing about pregnancy as the timeframe (as opposed to lifetime prevalence), and
      (2) a newly developed 4-item Drug CAGE using the same timeframe. The two
      instruments were assessed on sensitivity, specificity, and area under the
      receiver operating characteristic curve by using self-reported periconceptional
      heavier or problem alcohol and drug use as the criteria for the 12 months before
      knowing about the pregnancy. The results indicate that, for the Alcohol CAGE, the
      cut-point of 1 yielded the highest sensitivity, while maximizing sensitivity and
      specificity (receiver operating characteristic analysis) for this sample. For
      heavier drug use, the Drug CAGE had a high sensitivity rate with a cut-point of
      3. The Drug CAGE was not a useful screener for periconceptional lighter drug and
      marijuana use. These results demonstrate the utility of a revised version of the
      Alcohol CAGE that incorporates a more specific timeframe (the year before
      pregnancy) to screen pregnant, low-income women for at-risk heavier or problem
      alcohol use. The Drug CAGE, which uses the same timeframe, seems to be an
      effective tool for identifying pregnant, low-income women at risk for heavier
      drug use only. More psychometric works needs to be done to refine the Drug CAGE
      for detecting at-risk use of lighter drugs and marijuana.

PMID- 9514296
TI  - Voices of the afflicted.
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 those afflicted 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- 9514295
TI  - Alcohol consumption and sexually transmitted disease risk behavior: partner mix
      among male Korean university students.
AB  - BACKGROUND: This study examined alcohol consumption and sexually transmitted
      disease risk behavior as related to prostitute visits and sex partner mix among
      male Korean university students in 1993 to 1994. METHODS: Questionnaires were
      completed by a representative sample of 1103 university students in Seoul.
      Lifetime sexually transmitted disease risk behavior was categorized as none, only
      one, and multiple sexual experiences with prostitutes, whereas risk according to
      partner mix was classified as no sexual experience with prostitutes, sexual
      experience with prostitutes only, and with both prostitutes and girlfriends. The
      proportional odds model was applied to the data. RESULTS: A total of 25.8% of the
      university students had visited prostitutes--17.6% visited twice or more, and
      12.9% had sexual experiences with both prostitutes and girlfriends. Heavier
      alcohol consumption was significantly related to multiple visits to prostitutes
      (odds ratio = 1.71) and to sexual experiences with both prostitutes and
      girlfriends (odds ratio = 2.30). CONCLUSIONS: In this first systematic study of
      the association between alcohol consumption and sexual experiences among Korean
      male university students, alcohol use was associated with risky sexual behaviors,
      and with first and most recent sexual experience with prostitutes, supporting our
      hypotheses.

PMID- 9514297
TI  - Hypomagnesemia in alcoholic patients.

PMID- 9514299
TI  - Ethanol-induced neural crest apoptosis is coincident with their endogenous death,
      but is mechanistically distinct.
AB  - The ability of both acute and chronic ethanol exposures to elicit cell death
      within specific embryonic and adult tissues is believed to partly underlie
      ethanol's pathogenicity; however, the mechanism underlying this cell death is
      unknown. This study partially characterized the mechanism of ethanol-induced
      neural crest cell death in a chick embryo model of fetal alcohol syndrome. In
      situ DNA end-labeling demonstrated this cell death was apoptotic and occurred at
      embryonic ethanol levels as low as 42 mM. Regardless of the initial exposure
      time, this apoptosis always appeared at a distinct developmental time point
      simultaneous with the normal deletion of a cranial neural crest subset. This
      suggested that ethanol might act through aberrant activation of the endogenous
      death pathway; however, ethanol exposure failed to induce two components of this
      pathway, the homeotic transcription factor msx-2 and the growth factor bone
      morphogenetic protein 4. Both endogenous and ethanol-induced death were blocked
      by local application of an interleukin-1beta converting enzyme/CED-3 protease
      (caspase) inhibitor, showing that the two paths converge mechanistically and
      suggesting the potential to prevent this aspect of ethanol's teratogenicity.
      Ethanol exposure did not significantly alter cell proliferation within neural
      crest-populated regions, suggesting that susceptibility to ethanol-induced death
      did not involve exit from the cell cycle. Apoptotic deletion of cranial neural
      crest could partially explain the craniofacial deficits characteristic of the
      fetal alcohol syndrome.

PMID- 9514298
TI  - Acute ethanol intoxication inhibits neutrophil beta2-integrin expression in rats
      during endotoxemia.
AB  - The effects of acute ethanol intoxication on neutrophil [polymorphonuclear
      leukocyte (PMN)] adhesion molecule expression and certain other functional
      properties during endotoxemia were studied in rats to elucidate the mechanisms
      underlying the immunosuppressive effects of ethanol. Acute ethanol intoxication
      was induced by an intraperitoneal injection of 20% ethanol at a dose of 5.5 g of
      ethanol/kg. Control animals received an intraperitoneal injection of saline.
      Thirty minutes after intraperitoneal injection, animals were given a 90-min
      intravenous infusion of Escherichia coli endotoxin (total dose of 112.5
      microg/rat in 2.5 ml of saline) or saline. Certain rats received granulocyte
      colony-stimulating factor (G-CSF; 50 microg/kg in 5% dextrose, subcutaneous
      injection twice daily) or vehicle pretreatment for 2 days before intravenous
      endotoxin infusion. Endotoxemia significantly upregulated CD11b/c and CD18
      expression on PMNs when compared with those of saline-infused rats. Acute ethanol
      intoxication inhibited this endotoxin-induced upregulation of CD11b/c and CD18
      expression on PMNs. Ethanol intoxication also suppressed the phagocytic
      activities of PMNs in saline-infused rats, but this suppression failed to reach
      statistical significance in endotoxin-infused rats. Hydrogen peroxide generation
      by PMNs in saline- or endotoxin-infused rats was not affected by ethanol
      intoxication. Histological examination showed extensive PMN sequestration in the
      liver after endotoxin infusion, and ethanol intoxication significantly attenuated
      this hepatic sequestration of PMNs. G-CSF pretreatment enhanced neutrophil
      phagocytosis, CD11b/c and CD18 expression in endotoxin-infused rats, and
      prevented the ethanol-induced inhibition of neutrophil CD18 expression and
      phagocytosis. The impairment of beta2-integrin expression on PMNs may be one
      mechanism underlying ethanol-induced defects of neutrophil delivery into tissue
      sites of infection. G-CSF may be of benefit to the infected alcoholic host by
      enhancing leukocyte defense functions.

PMID- 9514300
TI  - Decreased tumor necrosis factor-alpha and interleukin-1alpha production from
      intrahepatic mononuclear cells in chronic ethanol consumption and upregulation by
      endotoxin.
AB  - The relationship between the changes in liver pathology and the production of
      interleukin (IL)-1alpha, IL-6, and tumor necrosis factor-alpha (TNF-alpha) by
      intrahepatic mononuclear cells was studied in rats fed alcohol and subsequently
      exposed to lipopolysaccharide (LPS). Rats were fed 40% ethanol in drinking water,
      whereas control rats were provided with a chow diet with isocaloric or 2% sucrose
      drinking solutions for up to 20 weeks. Decreased IL-1alpha and TNF-alpha
      production in 24-hr culture supernatants of mononuclear cells isolated from liver
      perfusate was detected while IL-6 remained unchanged over 20 weeks. When animals
      were injected with LPS (1.0 microg/kg body weight), there was a 5-fold rise in
      ALT levels in the ethanol-fed group, but not in control groups. Increased IL-6
      and TNF-alpha levels in the serum and supernatant of cultured intrahepatic
      mononuclear cells stimulated with or without LPS or concanavalin A was observed.
      There was a correlation between levels of ALT and TNF-alpha, but not IL-6. T
      cells and Kupffer cells were the major source of TNF-alpha in culture
      supernatants of hepatic perfusate mononuclear cells from ethanol-consuming rats
      injected LPS. In addition, pathological liver injury was evident, which suggests
      a pathogenic role for TNF-alpha in alcohol-induced liver disease.

PMID- 9514302
TI  - Varying effects of ethanol on transfected cell lines.
AB  - The use of transfected cell lines has provided a powerful approach to study the
      functions of transfected proteins. This approach has also proven useful to
      determine the effects of acute and chronic ethanol exposure on particular
      proteins. We show here, however, that the effects of ethanol on transfected
      proteins vary between transiently transfected cells and stably transfected cell
      lines. Moreover, we found that the effect of ethanol on a particular protein
      depends on the plasmid vectors used for the transfection.

PMID- 9514301
TI  - Adenoviral-mediated interferon-gamma gene therapy augments pulmonary host defense
      of ethanol-treated rats.
AB  - Alcohol has long been recognized as an immunosuppressive drug and a risk factor
      for a spectrum of infectious diseases. Among these infections, bacterial
      pneumonias are most closely correlated with alcohol abuse. One potential
      mechanism of ethanol-induced immunosuppression is through its ability to suppress
      alveolar macrophage production of tumor necrosis factor (TNF-alpha). This defect
      can be reversed by priming macrophages with interferon-gamma (IFN-gamma). We
      hypothesized that macrophage priming in vivo in a model of acute ethanol
      intoxication could augment pulmonary host defenses. To test this hypothesis, we
      used adenoviral-mediated gene transfer of the IFN-gamma gene. This strategy
      resulted in prolonged expression of IFN-gamma in vivo. Moreover, in a model of
      acute ethanol intoxication, this vector significantly enhanced lipopolysaccharide
      induced TNF-alpha responses and lung polymorphonuclear leukocyte recruitment.
      Furthermore, pulmonary host defenses against Klebsiella pneumoniae were
      significantly augmented. These enhanced host defenses were not reversed with
      pretreatment with a polyclonal anti-TNF-alpha antibody, suggesting that IFN
      gamma's effect was through a non-TNF-alpha-dependent mechanism. These data
      demonstrate that ethanol-induced suppression of pulmonary host defenses can be
      reversed with IFN-gamma gene therapy.

PMID- 9514303
TI  - Effect of ethanol on intracellular vesicular transport from Golgi to the apical
      cell membrane: role of phosphatidylinositol 3-kinase and phospholipase A2 in
      Golgi transport vesicles association and fusion with the apical membrane.
AB  - The study of ethanol effects on intracellular transport and membrane biogenesis
      in rat hepatocytes revealed that, during synthesis of transport vesicles, the
      cytosolic phosphatidylinositol 3-kinase incorporated into the membrane of Golgi
      transport vesicles and a portion of the vesicular phosphatidylinositol was
      phosphorylated to phosphatidylinositol 3-phosphate. Association of the enzyme
      with Golgi transport vesicles and the transport to the apical portion of the cell
      membrane was not affected by 0 to 120 mM ethanol, but was dependent on the
      presence of the p85 subunit of the phosphatidylinositol 3-kinase. In the presence
      of ATP-enriched cytosol and calcium ions, association of Golgi transport vesicles
      with the apical membrane was followed by phospholipase A2-specific hydrolysis of
      phosphatidylinositol 3-phosphate and incorporation of the transport vesicle
      membrane into the apical membrane. Association of Golgi transport vesicles with
      apical membranes was not affected by preincubation of the cell membrane or Golgi
      transport vesicles with 0 to 120 mM ethanol, but was inhibited when the p85
      phosphatidylinositol 3-kinase was incorporated into the membrane before
      incubation with Golgi transport vesicles. The fusion of Golgi transport vesicles
      with the apical membrane and generation of lysophosphatidylinositol 3-phosphate
      and arachidonate was inhibited with EGTA or after depletion of ATP from cytosol.
      Results of these studies provide evidence that phosphatidylinositol 3-kinase and
      phospholipase A2 activities are crucial for the final step of exocytotic
      transport. The process consists of two stages. First, the p85 subunit of
      phosphatidylinositol 3-kinase is involved in the specific association of the
      vesicle with membrane receptor, and that is followed by phospholipase A2-specific
      lysophospholipid generation, perturbation of the membranes, and fusion of the
      transport vesicle membrane with the apical membrane. Addition of ethanol to the
      in vitro transport system decreased production of Golgi transport vesicles, but
      had no effect on their association with apical membrane or fusion with the
      membrane.

PMID- 9514304
TI  - Metabolic mapping of the effects of oral alcohol self-administration in rats.
AB  - The functional effects of the voluntary consumption of ethanol in rats were
      investigated using the quantitative autoradiographic 2-[14C]deoxyglucose method
      for measurement of rates of local cerebral glucose utilization. A modified
      sucrose-substitution procedure was used to train three groups of Wistar rats to
      self-administer water, a 5% sucrose solution, or a 10% ethanol/5% sucrose
      solution in daily sessions. Once stable rates of consumption were established,
      the 2-[14C]deoxyglucose method was applied immediately after completion of the
      final test session. Rats received a dose of ethanol equivalent to 0.5 g/kg (n =
      6) on the day of the procedure or a comparable volume of sucrose solution (n = 6)
      or water (n = 5). Rates of local cerebral glucose utilization in rats that
      ingested water did not differ from those that rats consumed a 5% sucrose
      solution. In contrast, voluntary ethanol consumption produced a highly discrete
      pattern of changes in rates of glucose utilization. Ethanol ingestion increased
      cerebral metabolism, as compared with rates of metabolism in rats that consumed
      either water or sucrose in the rostral pole and shell of the nucleus accumbens,
      medial prefrontal cortex, lateral septum, basolateral and central nuclei of the
      amygdala, substantia nigra, and the ventral tegmental area. This pattern of
      alterations in functional activity is distinctly different from that observed
      when equivalent doses of ethanol are administered acutely, emphasizing the
      importance of self-administration in determining the changes in glucose
      utilization. Furthermore, within the nucleus accumbens, glucose utilization was
      selectively augmented in the rostral pole and shell subterritories, whereas
      cerebral metabolism in the core was unaffected. Finally, these data demonstrate
      that it is the simultaneous activation of an interconnected network of limbic
      brain regions that serves as the substrate of the effects of voluntarily ingested
      ethanol.

PMID- 9514305
TI  - Acamprosate enhances N-methyl-D-apartate receptor-mediated neurotransmission but
      inhibits presynaptic GABA(B) receptors in nucleus accumbens neurons.
AB  - Acamprosate (calcium acetylhomotaurine) is used therapeutically in Europe to
      reduce relapse in weaned alcoholics. However, the mechanisms of acamprosate
      action in the central nervous system are still obscure, although early studies
      suggested an action on GABA receptors. The nucleus accumbens (NAcc) is a brain
      region thought to underlie ethanol reinforcement. Recent studies from our
      laboratory have demonstrated that ethanol inhibits both N-methyl-D-aspartate
      (NMDA) and non-NMDA types of glutamatergic synaptic transmission in the NAcc. In
      the present study, we used voltage- and current-clamp intracellular recording of
      NAcc core neurons in a slice preparation to examine acamprosate actions on
      resting membrane properties and pharmacologically isolated synaptic responses. We
      isolated NMDA and non-NMDA receptor-mediated excitatory postsynaptic potentials
      or currents (EPSP/Cs) with 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and DL-2
      amino-5-phosphonovalerate (d-APV), respectively. Bicuculline was also included to
      block GABA(A) receptors. Superfusion of acamprosate (5, 50, and 300 microM) did
      not alter the resting membrane properties of NAcc neurons. However, 300 microM
      acamprosate significantly increased the NMDA receptor-mediated components of
      EPSP/Cs (NMDA-EPSP/Cs) with recovery on washout. In contrast, 300 microM
      acamprosate had no significant effect on the non-NMDA receptor component of the
      EPSP/Cs (non-NMDA-EPSP/Cs). To test acamprosate actions on the GABA system, we
      superfused 60 microM d-APV and 20 microM CNQX to block glutamatergic transmission
      and evoked monosynaptic GABA(A) receptor-mediated synaptic responses within the
      NAcc. Acamprosate (300 microM) did not change these monosynaptic GABA(A)-IPSCs.
      We also used a paired-pulse paradigm to test whether acamprosate could act on
      presynaptic GABA(B) autoreceptors, in the presence of d-APV and CNQX to block
      glutamatergic transmission. Like 0.5 microM CGP 34358 (a GABA[B] receptor
      blocker), acamprosate significantly decreased the paired-pulse inhibition (PPI)
      of GABA(A)-IPSCs at short interstimulus intervals (ISIs). Thus, acamprosate may
      concomitantly enhance NMDA-EPSP/Cs while blocking presynaptic GABA(B) receptor
      mediated inhibition of GABA release. These results suggest that acamprosate's
      clinical efficacy in preventing relapse in weaned alcoholics could derive from
      its interactions with both the glutamatergic and GABAergic systems in the NAcc.

PMID- 9514306
TI  - Increased circulating products of lipid peroxidation in patients with alcoholic
      liver disease.
AB  - F2-isoprostanes (F2-IP) and 4-hydroxynonenal (4-HNE), peroxidation products of
      polyunsaturated fatty acids (PUFA), are considered the most reliable indicators
      of endogenous lipid peroxidation in vivo. To determine to what extent these are
      also altered in patients with alcoholic liver disease, plasma free and esterified
      F2-IP as well as 4-HNE were measured by GC/MS in 49 fasting subjects who
      underwent diagnostic percutaneous needle biopsies of the liver. Compared to
      patients with mild steatosis and no fibrosis, free F2-IP and 4-HNE were
      strikingly increased in individuals with alcoholic hepatitis. There was also a
      significant but lesser rise of 4-HNE in patients with perivenular fibrosis. An
      increase of F2-IP was also found in subjects with transition to, or complete,
      alcoholic cirrhosis, with a comparable trend for 4-HNE. By contrast, in patients
      who were drinking heavily up to 48 hr before admission, F2-IP were not abnormal,
      but they increased later (p < 0.005). Contrasting with plasma free F2-IP,
      esterified F2-IP were not significantly changed with fibrosis. Thus, whereas
      circulating esterified F2-IP were unchanged in patients with alcoholic liver
      disease, there was an increase in free F2-IP as well as 4-HNE during recovery
      from intoxication. The increase was not a result of accompanying hepatitis C but
      a function of the stage of alcoholic liver injury, possibly reflecting enhanced
      lipid peroxidation as well as interference with biliary excretion and/or hepatic
      esterification.

PMID- 9514307
TI  - Circulating neutrophils and liver injury in rat models of experimental alcoholic
      liver disease.
AB  - The present study examined the relationship between circulating neutrophils and
      liver injury in two widely used rat models of chronic ethanol administration.
      Hematological alterations, liver histopathology, and biochemical indices of liver
      injury were assessed in rats receiving chronic ethanol by oral liquid diet
      feeding (Lieber-DeCarli method) or by continuous intragastric infusion (Tsukamoto
      French method). Oral administration of ethanol did not affect circulating
      neutrophil counts, but resulted in minimal liver injury characterized by elevated
      serum alanine aminotransferase (79%), increased liver mass (15%), and moderate
      steatosis. In contrast, rats receiving ethanol by continuous intragastric
      infusion showed an approximately 2-fold increase in circulating neutrophils, and
      a moderate degree of liver injury, indicated by a 169% elevation of serum alanine
      aminotransferase and a 2-fold increase in liver mass. Liver biopsies from these
      rats showed severe steatosis and scattered necrotic hepatocytes, and some
      neutrophil infiltrates. To determine whether an increase in the number of
      circulating neutrophils could potentiate liver injury induced by oral ethanol
      feeding, rats were treated with human recombinant granulocyte colony-stimulating
      factor at a dose of 100 microg/kg/day (s.c.) for 4 days. Treatment with
      granulocyte colony-stimulating factor resulted in a 6- to 9-fold increase in
      circulating neutrophil counts. Nevertheless, this change did not enhance the
      minor degree of ethanol-induced liver injury in this model. Our results indicate
      that, whereas neutrophil leukocytosis accompanies more severe manifestations of
      ethanol hepatotoxicity in rats, this condition per se does not directly induce or
      exacerbate ethanol-induced liver injury.

PMID- 9514308
TI  - Clamping breath alcohol concentration reduces experimental variance: application
      to the study of acute tolerance to alcohol and alcohol elimination rate.
AB  - An oral loading dose was combined with intravenous infusion of 6% alcohol at
      rates adjusted on-line to close the gap between measurements of breath alcohol
      concentration (BrAC) and a target of 50 mg%. The goal was to minimize the
      deviation from a prescribed course of BrAC over time. In a pilot study of 10
      young men, subjects underwent three experimental sessions: twice at 50 mg% and
      once in a 0 mg% control condition. The pilot study assessed the performance of
      the BrAC clamp, its potential utility in studies of acute tolerance to alcohol,
      and the retest reliability of directly measuring the alcohol elimination rate
      (AER) calculated from the steady-state infusion rate. Reduced variance was
      demonstrated in 4 of 5 experimental parameters, compared with results of an
      earlier approach using a split-dose oral administration procedure. Subjects'
      perceptions about alcohol effects were measured in one BrAC clamping session,
      using Schuckit's Subjective High Assessment Scale: 3 of 15 Schuckit's items
      demonstrated statistically significant indices of acute tolerance to alcohol.
      Within-subject AERs calculated in the steady-state had a coefficient of variation
      of 6.5%. Details of the BrAC clamping procedure are provided. The pilot study
      demonstrated the ability to prescribe experimental parameters of the brain's
      exposure to alcohol while preserving experimental flexibility in studies of acute
      tolerance to alcohol and AER.

PMID- 9514309
TI  - Regulation of monocyte interleukin-12 production by acute alcohol: a role for
      inhibition by interleukin-10.
AB  - Acute ethanol treatment results in decreased antigen presentation capacity (Th1
      type immunity) and elevated interleukin IL-10 (Th2 cytokine) production in human
      monocytes. Monocytes can contribute to both Th1 (IL-12) and Th2 (IL-10) immune
      responses via production of IL-12 and IL-10, respectively. Thus, we tested the
      hypothesis that acute alcohol treatment might affect Th1/Th2 immune balance by
      altering monocyte production of IL-12 and IL-10. Neither acute ethanol treatment
      alone (25 to 100 mM) nor its combination with a bacterial challenge
      Staphylococcal enterotoxin B (SEB) induced IL-12 production in isolated blood
      monocytes. In contrast, the same physiological alcohol concentrations increased
      monocyte IL-10 levels, suggesting that ethanol can induce a dysbalance of
      monocyte-derived mediator production at the expense of Th1 cytokines. However, we
      found that monocyte activation with interferon-gamma (IFN-gamma) can prevent the
      preferential IL-10 induction by ethanol. IFN-gamma (100 units/ml) inhibited
      monocyte IL-10 production whether induced by 1 microg/ml of lipopolysaccharide (p
      < 0.01), 1 microg/ml of SEB (p < 0.02), or a combination of bacterial stimulation
      + ethanol (lipopolysaccharide: p < 0.01). Furthermore, decreased IL-10 was
      concomitant to an increase in IL-12 production in IFN-gamma-treated monocytes.
      Moreover, acute ethanol treatment augmented IL-12 production in IFN-gamma-treated
      monocytes in response to SEB stimulation (25 mM ethanol, p < 0.01; 100 mM
      ethanol, p < 0.01). Experiments with anti-IL-10 neutralizing antibody show that
      ethanol may prevent monocyte IL-12 induction via IL-10. These results suggest
      that inhibition of ethanol-induced IL-10 production by IFN-gamma treatment is
      permissive for IL-12 induction by alcohol stimulation in monocytes. Thus, our
      results imply that the presence or absence of IFN-gamma is critical in
      determining the effect of acute ethanol treatment on monocyte IL-12 versus IL-10
      induction.

PMID- 9514310
TI  - Brain neuronal degeneration caused by episodic alcohol intoxication in rats:
      effects of nimodipine, 6,7-dinitro-quinoxaline-2,3-dione, and MK-801.
AB  - Rats repeatedly intoxicated with alcohol (ethanol, three times daily) over a 4
      day period display neuronal degeneration in the dentate gyrus; entorhinal,
      piriform, insular, orbital, and perirhinal cortices; and in the olfactory nerve
      fibers and terminals in the olfactory bulb. Postulating a role for
      excitotoxicity, we have attempted to prevent the degeneration using antagonists
      that are neuroprotective in this type of brain damage. In an initial study,
      continuous subcutaneous infusion of a high dose of the glutamate/NMDA receptor
      antagonist MK-801 (2 mg/kg/day) by itself caused extensive neuronal degeneration
      in several brain regions and severe behavioral intoxication that precluded
      survival if combined with high blood alcohol levels (approximately 300 mg/dl).
      Moreover, the lower, nonneurotoxic blood alcohol levels (approximately 150 mg/dl)
      that were compatible with survival worsened the MK-801-induced brain damage. In a
      subsequent experiment, daily intraperitoneal injections of a lower dose of MK-801
      (1 mg/kg/day) resulted in no MK-801 toxicity and, when combined with neurotoxic
      levels of alcohol, no reduction in alcohol-induced neurotoxicity. Nimodipine, a
      voltage-gated Ca2+ channel blocker, reduced the neuronal damage in the dentate
      gyrus, but greatly increased it in the piriform cortex when administered
      intragastrically at 600 mg/kg/day; it provided no protection from alcohol
      dependent degeneration when given intragastrically at 100 mg/kg/day. Continuous
      intracerebroventricular delivery of 0.24 to 0.29 mg/day of 6,7-dinitro
      quinoxaline-2,3-dione, a glutamate/alpha-amino-3-hydroxy-5-methyl-4-isoxazole
      receptor antagonist, failed to diminish alcohol-dependent neuronal damage in any
      brain region. We conclude that brain damage from episodic "binge" alcohol
      intoxication is not primarily mediated by excitotoxic mechanisms, implying that
      other, nonexcitotoxic pathophysiological mechanisms, are involved. Furthermore,
      MK-801, far from protecting from the alcohol-induced damage, at high doses causes
      widespread neuropathology that is significantly potentiated by alcohol.

PMID- 9514311
TI  - Ethanol exposure potentiates fosB and junB expression induced by muscarinic
      receptor stimulation in neuroblastoma SH-SY5Y cells.
AB  - Muscarinic receptor stimulation and activation of protein kinase C cause an
      increase in fosB and junB transcripts in human neuroblastoma SH-SY5Y cells. In
      this study, the effect of long-term ethanol exposure on these events was
      investigated. Carbachol-stimulated fosB and junB expression was elevated in
      ethanol-exposed cells compared with control cells. The potentiation was time- and
      dose-dependent on ethanol. Preincubation with muscarinic antagonists or protein
      kinase C inhibitor demonstrated that the carbachol-stimulated increase in fosB
      and junB mRNA levels was primarily mediated via M1 receptors and dependent on the
      activity of protein kinase C in both control and ethanol-exposed cells. Long-term
      ethanol exposure did not influence the expression of fosB and junB induced by
      activation of protein kinase C with phorbol ester. These results demonstrate that
      the muscarinic receptor-stimulated fosB and junB expression is sensitive to
      ethanol exposure in SH-SY5Y cells, suggesting that these genes participate in the
      regulation of neuronal function in response to chronic ethanol treatment.

PMID- 9514312
TI  - Electrophysiological assessment (The Multiple Sleep Latency Test) of the biphasic
      effects of ethanol in humans.
AB  - The Multiple Sleep Latency Test (MSLT) was used to assess the effects of ethanol
      at the peak and descending phases of the breath ethanol curve. Ethanol (0.75
      g/kg) was administered (at 0900 hr) to 8 healthy, normal-sleeping men, aged 21 to
      45 years old after 8 hr of sleep the previous night. MSLTs were conducted and
      breath ethanol concentrations (BrECs) were measured at 15, 45, 75, 105, 225, and
      345 min after drinking was completed. Subjective measures were administered
      immediately before each sleep latency test. BrECs over the first 75 min (tests 1
      to 3) peaked and differed from all subsequent tests (tests 4 to 6) over which
      BrECs declined. Sleep latency and subjective measures were averaged over tests 1
      to 3 and 4 to 6. There was a significant increase in mean sleep latency relative
      to placebo for tests 1 to 3 and a significant reduction for tests 4 to 6. The
      subjective measure of stimulation sedation, the Biphasic Alcohol Effects Scale,
      showed lessened sedation after ethanol versus placebo on tests 1 to 3, compared
      with tests 4 to 6. This study confirmed the presence of a biphasic ethanol effect
      using an electrophysiological method (MSLT), showing increased physiological
      alertness on the peak phase of the BrEC curve and increased sedation on the
      descending phase. Relative to the effects observed on the MSLT with other low
      dose stimulant drugs, the stimulatory effect of ethanol was mild.

PMID- 9514313
TI  - The effects of ethanol on dopaminergic neurons of the ventral tegmental area
      studied with intracellular recording in brain slices.
AB  - Dopaminergic neurons in the ventral tegmental area of Tsai (VTA) have been
      implicated in the mediation of the rewarding effects of ethanol and many other
      drugs of abuse. Our previous extracellular studies in brain slices have
      demonstrated that ethanol increases the firing rate of dopaminergic neurons in
      the VTA. In the present intracellular study, ethanol (40-160 mM) increased the
      spontaneous firing rate of most (77%) VTA neurons. In addition, most (75%) VTA
      neurons were depolarized by ethanol. Ethanol also changed the shape of the
      spontaneous action potential in VTA neurons, reducing the amplitude of the spike
      after-hyperpolarization (in 74% of neurons) and also reducing the amplitude of
      the depolarizing phase of the action potential (in 86% of neurons tested).
      Furthermore, analysis of Voltage/Current curves in the presence and absence of
      ethanol showed that ethanol had little effect on the resistance of the cell
      membrane at membrane potentials near rest, but enhanced the time-dependent inward
      rectification activated at more hyperpolarized membrane potentials (Ih). This
      intracellular study identifies several electrophysiological effects of ethanol
      that may underlie the ethanol-induced excitation of VTA neurons and, therefore,
      may be important for the rewarding effects of ethanol.

PMID- 9514314
TI  - Interleukin-12 therapy restores cell-mediated immunity in ethanol-consuming mice.
AB  - Previous studies from our laboratory show that ethanol consumption impairs
      antigen-specific, cell-mediated, but not, humoral immune responses of C57BL/6,
      BALB/c, and DO11.10 T-cell receptor transgenic mice. This ethanol-associated
      deficit is associated with decreased interleukin (IL)-12 and interferon-gamma
      (IFN-gamma) production, but not IL-2 or antigen-specific T-cell proliferation by
      explanted leukocytes from ethanol-consuming mice. IL-12 expression by
      macrophage/monocytes is viewed as a requirement for the production of IFN-gamma
      by Th1 lymphocytes that mediate cellular immunity. In this study, we restored
      antigen-specific, cell-mediated immunity, delayed hypersensitivity, to ethanol
      consuming C57BL/6 or BALB/c mice with a single 100 ng of intravenous injection of
      recombinant IL-12 at the time of immunization. The addition of exogenous
      recombinant IL-12 to co-cultures of antigen-presenting cells derived from ethanol
      consuming mice and purified T cells derived from ethanol-nonconsuming DO11.10
      repairs the ability of Th1 cells to make IFN-gamma in response to antigen.
      Administration of recombinant IL-12 opens a potential for restoring cell-mediated
      immune function to ethanol-consuming individuals.

PMID- 9514315
TI  - Prenatal exposure to alcohol affects the ability to maintain postural balance.
AB  - Prenatal exposure to alcohol is known to affect gross motor functioning. Animal
      studies have shown that balance is particularly affected, and there is some
      evidence that similar deficits exist in alcohol-exposed children. In the current
      study, postural balance, or the ability to maintain equilibrium, was assessed in
      a group of alcohol-exposed children (ALC group; n = 11) and controls (NC group; n
      = 11) individually matched for age and sex. Balance was measured across six
      conditions designed to systematically manipulate or eliminate visual or
      somatosensory information. Equilibrium and strategy scores for each condition and
      a derived composite balance score were analyzed. Although the ALC group had a
      lower mean composite balance score, their performance was similar to that of the
      NC group on all conditions where somatosensory input was reliable. However, when
      somatosensory input was manipulated, and when both somatosensory and visual input
      were inaccurate, the ALC group performed more poorly than controls.
      Interestingly, there were no differences between the ALC group and NC group in
      the type of control strategy used to maintain balance. These results suggest that
      alcohol-exposed children are overly reliant on somatosensory input. When this
      input is atypical, alcohol-exposed children display significantly greater
      anterior-posterior body sway and are unable to compensate using available visual
      or vestibular information. These deficits may be related to cerebellar anomalies
      previously reported in fetal alcohol syndrome children.

PMID- 9514316
TI  - Ethanol tolerance and withdrawal responses in GABA(A) receptor alpha 6 subunit
      null allele mice and in inbred C57BL/6J and strain 129/SvJ mice.
AB  - We have been using a genetic strategy to define the contribution of specific
      candidate genes, such as those encoding subunits of the gamma-aminobutyric acid
      type A receptor, to various ethanol sensitive responses. We have used the gene
      knockout approach in mouse embryonic stem cells to create mice in which the gene
      encoding the alpha6 subunit of the gamma-aminobutyric acid type A receptor is
      rendered nonfunctional. In the present report, we provide a detailed
      characterization of several behavioral responses to ethanol in these null allele
      mice. In a separate series of experiments, behavioral response to ethanol was
      compared between two inbred strains of mice that are commonly used as background
      stock in knockout experiments, namely C57BL/6J and Strain 129/SvJ. Wild type
      (alpha6+/+) and homozygous null allele (alpha6-/-) mice did not differ to the
      ataxic effects of ethanol on acute functional tolerance (95.8 +/- 8.7 vs. 98.8 +/
      5.7 mg/dl +/- SEM, respectively). Withdrawal hyperexcitability was assessed
      following chronic exposure to ethanol vapor (EtOH) or air (CONT) in inhalation
      chambers in a multiple withdrawal treatment paradigm. At the end of the last
      treatment cycle, mice were scored for handling induced convulsions (HIC). After
      adjusting for differences in blood ethanol concentration between genotypes at the
      end of the final treatment cycle, we observed a greater area under the 24-hr HIC
      curves in mice treated with ethanol (p < 0.0001) but did not detect an effect of
      genotype (alpha6+/+/CONT 3.1 +/- 2.0; alpha6-/-/CONT 5.5 +/- 2.5; alpha6+/+/EtOH
      30.1 +/- 6.2; alpha6-/-/EtOH 33.0 +/- 5.8 mean units +/- SEM). We also examined
      these mice for differences in protracted tolerance; at approximately 26 hr into
      the final withdrawal cycle, each mouse was injected with ethanol (3.5 mg/g body
      weight) and sleep time was measured. We detected a significant effect of
      treatment (p < 0.001) with ethanol-treated mice demonstrating signs of tolerance
      as reflected by a reduction in duration of sleep time. However, effect of
      genotype was not significant (alpha6+/+/CONT 57.4 +/- 7.6; alpha6-/-/CONT 59.0 +/
      7.6; alpha6+/ +/EtOH 34.8 +/- 7.4; alpha6-/-/EtOH 30.8 +/- 5.6 min +/- SEM).
      From these data we conclude that the alpha6 subunit of the GABA(A)-R exerts
      little if any influence on acute functional tolerance, withdrawal
      hyperexcitability, or protracted tolerance. Strain 129/SvJ and C57BL/6J mice were
      also compared for acute functional tolerance and were found not to differ (96.3
      +/- 4.4 vs. 94.8 +/- 11.3 mg/dl +/- SEM, respectively). Withdrawal
      hyperexcitability was assessed by comparing the area under the 24 hr HIC curves.
      Strain 129/SvJ mice displayed a much greater basal HIC response compared to
      C57BL/6J mice (19.8 +/- 4.3 vs. 0.2 +/- 0.2 mean units +/- SEM, respectively);
      after adjusting for differences in blood ethanol concentration between strains at
      the end of the final ethanol treatment cycle, the HIC response was markedly
      enhanced by ethanol treatment in Strain 129/SvJ mice but not in C57BL/6J mice
      (50.4 +/- 3.1 vs. 9.5 +/- 5.4 mean units +/- SEM, respectively). The effects of
      treatment (p < 0.0001), strain (p < 0.0001), and the interaction of strain with
      treatment (p < 0.01) were significant. Since many gene knockout mice are
      maintained on a mixed genetic background of Strain 129/SvJ and C57BL/6J, we
      conclude that significant differences in tests of withdrawal hyperexcitability
      may be confounded by the influence of genes that cosegregate with the gene
      targeted allele.

PMID- 9514317
TI  - Additive reduction of alcohol drinking by 5-HT1A antagonist WAY 100635 and
      serotonin uptake blocker fluoxetine in alcohol-preferring P rats.
AB  - We found previously that alcohol-preferring (P) rats have fewer serotonin (5-HT)
      neurons and fibers in key brain regions than alcohol-nonpreferring (NP) rats.
      Because 5-HT uptake blockers increase synaptic 5-HT content and 5-HT1A receptor
      antagonists increase 5-HT release by disinhibiting 5-HT autoinnervation, in the
      present study, our intent was to determine whether increased synaptic 5-HT
      content and/or 5-HT release in P rats would effectively reduce alcohol
      consumption. In experiment 1, the 5-HT antagonist WAY 100635 (WAY) was tested on
      adult female P rats maintained on 24-hr free-choice access to ethanol (10% v/v)
      and water. Twice daily doses of WAY (0.05, 0.1, 0.5, and 1.0 mg/kg,
      subcutaneously) were administered to each rat in a counterbalanced order.
      Baseline ethanol intake, derived from the mean ethanol intakes of the three
      previous non-drug days, was approximately 8 g/kg/day. Results indicated that
      0.05, 0.1, and 0.5 mg/kg doses of WAY reduced 24-hr ethanol drinking by 25-30% (p
      < 0.01) without affecting 24-hr water intake or body weight. In the second
      experiment, the effects of WAY (0.5 mg/kg), fluoxetine (1.0 mg/kg), or a
      combination of both were tested in another group of female P rats. WAY and
      fluoxetine, each alone, reduced ethanol drinking by around 20% and, when
      combined, decreased ethanol intake by 50%, whereas the body weight and the total
      fluid intake were not significantly affected. Taken together, these results
      indicate that both fluoxetine and WAY preferentially reduce ethanol drinking in
      the P line of rats and, when administered together, reduce ethanol intake in an
      additive manner. It is proposed that coadministration of these two compounds with
      distinct mechanisms of action may be a new strategy for reducing alcohol intake.

PMID- 9514318
TI  - Neonatal ethanol exposure impairs eyeblink conditioning in weanling rats.
AB  - Eyeblink conditioning depends on an identified brainstem-cerebellar circuit and
      may be useful in functional studies of early cerebellar damage produced by
      neurotoxicants. The present study asked whether binge-like neonatal ethanol
      exposure that damages the cerebellum would also result in eyeblink conditioning
      deficits. On postnatal day (PND) 23 to PND24, three groups of Long-Evans rat pups
      were tested for eyeblink conditioning: (1) ETOH, a group that received
      intragastric administration of 5.25 g/kg/day of ethanol on PND4 through PND9 via
      artificial rearing; (2) GC, a gastrostomy control group that received calorically
      matched milk formula on those days; and (3) SC, suckle controls that were reared
      normally with their dams. Eyeblink conditioning was severely impaired in the
      ethanol-treated group relative to the GC and SC groups, which did not differ.
      This impairment did not reflect sensory, motor, or motivational effects of
      ethanol treatment, because startle responses to the auditory conditioned stimulus
      and reflexive eyeblink responses to the unconditioned stimulus did not differ
      across the three treatment groups. These results suggest that neonatal binge
      ethanol exposure disrupted brain development in a manner that selectively
      impaired associative processes involved in eyeblink conditioning, consistent with
      alcohol-induced damage to the brainstem-cerebellar circuit necessary for this
      form of learning.

PMID- 9514319
TI  - Considerations on stimulated anal neosphincter formation: an anatomic
      investigation in search of alternatives to the gracilis muscle.
AB  - Electrically stimulated anal neosphincter formation with transposed gracilis is
      performed clinically in an increasing number of patients. The use of a stimulated
      gluteus maximus in this application has been reported also. The question arises
      whether or not an optimal design for such a procedure has already been
      ascertained. An anatomic study was performed on 30 human cadavers to evaluate the
      semitendinosus muscle and its suitability for construction of a stimulated anal
      neosphincter. Semitendinosus fulfilled requirements for transposition around the
      anal canal in all cases. The muscle length was found adequate for transposition;
      nerve and vascular supply provided a suitable arc of rotation. The pattern of
      innervation might allow selective stimulation of that particular part of the
      muscle, which is intended to restore sphincter function. For clinical
      application, a vascular delay procedure is strongly recommended.

PMID- 9514320
TI  - Evolving thoughts on correcting posttraumatic enophthalmos.
AB  - Posttraumatic enophthalmos, though a difficult problem, is correctable by
      traditional craniofacial techniques. Based on considerable experience with these
      wide exposure operations, our surgical strategy has evolved and has been
      distilled into one of limited exposure via lateral upper blepharoplasty,
      transconjunctival without canthotomy and intraoral incisions. The advantages of
      this approach are reduced morbidity and hospital stay, shorter operating time,
      and avoidance of blood transfusions. However, this technique should be reserved
      until valuable insight is gained using the more conventional coronal approach.

PMID- 9514321
TI  - Nonsurgical correction of congenital auricular deformities in children older than
      early neonates.
AB  - It has been reported that nonsurgical correction of auricular deformities is not
      effective except in early neonates. We have succeeded in nonsurgical correction
      using thermoplastic splints for congenital auricular deformities on 50 ears of 45
      patients without severe hypoplasia in children older than 1 year. Details of the
      types of ears we attempted to treat were 26 cryptotias, 5 lop ears, 5 Stahl's
      ears, 3 prominent ears, 3 shell ears, and 8 other miscellaneous conditions. The
      patients were between 1 and 14 years of age with an average age of 3.6 years. Our
      results were categorized as follows: excellent (the auricle was delicately
      corrected into a desirable form and satisfied the patient), improved (the auricle
      was corrected into a rough form that did not attain to a desirable shape and an
      irregular form still remained; however, its improvement satisfied the patient),
      recurrent (the auricle was initially corrected but the deformity recurred), not
      improved (the auricle was not corrected to the desired form and the result did
      not satisfy the patient), and gave up (the patient gave up before treatment could
      be completed). In our results, the average period of splint application was 2.1
      months. In 27 of the 50 cases, the treated ears were excellent. Eleven ear cases
      showed improvement. Six cases showed recurrence. Three cases did not improve.
      Three patients gave up treatment. It is suggested that nonsurgical auricular
      correction is possible in almost all children, even if they are not early
      neonates, when corrections are made continuously and gradually.

PMID- 9514322
TI  - A comparative study of the lateral crus of alar cartilages in unilateral cleft
      lip nasal deformity.
AB  - To confirm whether or not the alar cartilage of the unilateral cleft lip nose is
      primarily hypoplastic as compared with the noncleft side, 35 unilateral cleft lip
      nasal patients who had no previous nasal surgery underwent direct measurement of
      the lateral crus of alar cartilage on both sides during their nasal tip plasties.
      Both lower lateral cartilages were dissected freely, and the thickness was
      measured at the intercrural, middle, and distal portions. The width was measured
      at the widest portion, and the length was measured from the intercrural point to
      the distal end. Two-mm-punch biopsies were obtained from each cartilage for
      histologic study. The lateral crus of the cleft side was no smaller than that of
      the noncleft side. Histologically, no difference was ascertained. In conclusion,
      we think the lateral crus of the alar cartilage of the cleft side is not
      hypoplastic. Therefore, external factors such as soft-tissue defect or external
      abnormal vector force are more attributable than intrinsic factors to the
      development of cleft lip nasal deformity.

PMID- 9514323
TI  - Fibula osteoseptocutaneous flap for reconstruction of osteoradionecrosis of the
      mandible.
AB  - Osteoradionecrosis of the mandible poses formidable problems for treatment. In
      the last 6 years, the fibula osteoseptocutaneous free flap was used in 12 cases
      to replace mandibles with radionecrotic damage. The presence of a pathologic
      fracture, exposed necrotic bone, or a persistent fistula not responding to
      conservative treatment were the indications for such a radical approach. Mandible
      defects after resection were around 8.0 cm long, and in all cases intraoral
      mucosa, skin, or both were included with the bone excision. All vascularized
      fibula osteoseptocutaneous flaps transplanted were successful with good primary
      bone healing. Adequate facial symmetry and improvement in oral function was
      achieved. No evidence of osteoradionecrosis recurrence was observed after a mean
      follow-up period of 3 years and 9 months. The advantages of using the fibula
      osteoseptocutaneous flap for mandible reconstruction are numerous, and good
      aesthetic and functional results can be obtained when it is used for
      reconstruction after radical excision of osteoradionecrotic lesions.

PMID- 9514324
TI  - Reconstruction of upper cranial and cranial base defects utilizing the scalping
      flap.
AB  - Reconstruction of midfacial defects by means of a scalping flap has been widely
      practiced and described in the literature. The advantages of the flap are
      familiar to surgeons who perform extirpations and reconstruction of the head and
      neck and include contiguous availability, simplicity of application, and a robust
      and redundant blood supply. Despite these merits, the flap has not been widely
      used for reconstructions of large anterior cranial defects or defects of the
      cranial base. A retrospective review of 11 patients who underwent reconstructions
      between 1990 and 1995 was performed. In each case, a reconstruction of a large
      anterior cranial or cranial base defect was carried out. The resulting soft
      tissue defect was restored via the scalping flap. In six cases, this was carried
      out in a single procedure. In five cases, flap division and insetting were
      carried out in a subsequent procedure, following a 1- to 2-week delay. In all
      cases, the extirpation and reconstruction were well tolerated, and the average
      time of hospitalization was 5.9 days and ranged from 3 to 11 days. No major
      surgical complications occurred. One of 11 patients had a minor complication not
      requiring surgical intervention. There was one recurrence of a cranial base tumor
      approximately 2 years following the initial resection and reconstruction. In all
      cases, the final aesthetic and functional results were acceptable to excellent.
      Follow-up ranged from 11 months to 5 years. In conclusion, the scalping flap can
      be effectively utilized for soft-tissue coverage in the reconstruction of
      anterior cranial and cranial base defects. Use of this simple and versatile flap
      in craniofacial reconstruction is well tolerated and is associated with a low
      morbidity, a good aesthetic result, and a short hospital stay.

PMID- 9514325
TI  - Tracheal reconstruction using a free jejunal flap with cartilage skeleton:
      experimental study.
AB  - An experimental study was undertaken to evaluate the behavior of an autologous
      microvascularjejunal transfer with a cartilage skeleton for major tracheal
      reconstruction in the goat model. A 15-cm segment of the cervical trachea was
      replaced by a free microvascularjejunal transfer with costal cartilage skeleton
      as a single-stage procedure. The flap was stented for 4 weeks with an
      endotracheal T-tube. Bronchoscopy was done to the survivors at 6 months. The
      perioperative mortality rate was 40 percent, with 30 percent of the animals
      surviving the 30-week follow-up period. Bronchoscopy showed a smooth and
      appropriate lumen. Histology showed hyaline cartilage integrated within the
      jejunal wall and normal jejunal mucosa. The reconstruction of a large
      circumferential tracheal defect with a free jejunal transfer with cartilaginous
      skeleton remained stable, without undue mucous secretion, and the surviving
      animals remained asymptomatic for the follow-up.

PMID- 9514326
TI  - Role of buttress reconstruction in zygomaticomaxillary skeletal defects.
AB  - The purpose of this study was to review eight patients undergoing midfacial
      skeletal reconstruction following extensive resection of tumors based on the
      principles of restoration of three maxillary buttresses, the nasomaxillary,
      zygomaticomaxillary, and pterygomaxillary. The zygomaticomaxillary skeletal
      defects were reconstructed with a three-dimensionally contoured piece of titanium
      mesh, vascularized costal cartilage, or vascularized bone flap of scapula and
      rib. Restoration of the zygomaticomaxillary buttress prevented the inferior
      deviation of the orbit and provided good zygomatic contour. Restoration of the
      nasomaxillary buttress prevented the superior and posterior deviation of the alar
      base of the nose, and restoration of the pterygomaxillary buttress prevented the
      superior and posterior deviation of the upper lip. Combination of the V-shaped
      scapular bone and the rib flap based on the thoracodorsal vascular system, which
      provides simultaneous reconstruction of all three buttresses, is a very versatile
      technique for reconstruction of extended midfacial skeletal defects. In this
      series, both of the patients reconstructed with titanium mesh presented with late
      persistent cutaneous fistulas. We now recommend a vascularized autologous soft
      and bony tissue reconstruction for midfacial composite defects.

PMID- 9514327
TI  - Maxillary distraction: aesthetic and functional benefits in cleft lip-palate and
      prognathic patients during mixed dentition.
AB  - In the last few years, distraction techniques have been used successfully to
      correct the hypoplastic human mandible. In patients with cleft lip and palate,
      normal growth of the maxilla may be impaired by early cleft repair, and many of
      them do not respond to orthodontic procedures alone. Maxillary distraction is an
      alternative technique to correct maxillary hypoplasia during mixed dentition. In
      the last 3 years, the procedure was performed in 38 patients aged between 6 and
      12 years; 18 patients had unilateral cleft lip and palate, 9 patients had
      bilateral cleft lip and palate, 7 patients had unilateral cleft palate, 2
      patients had prognathism, and 2 patients had nasomaxillary dysplasia.
      Photographs, posteroanterior and lateral cephalograms, and dental models are
      obtained preoperatively (as well as an orthopantomogram) to locate the tooth
      buds. A subperiosteal dissection is performed exposing the anterior and lateral
      aspects of the maxilla, and an incomplete horizontal osteotomy is done above the
      tooth buds. Using a facial mask and an intraoral fixed appliance system as an
      anchorage, we initiate on the fifth postoperative day the application of
      distraction forces. Maxillary advancement between 4 and 12 mm is achieved during
      3 to 4 weeks, and a satisfactory class I or II molar relationship is also
      obtained. A combination of forward and downward distraction forces can be used to
      achieve simultaneous advancement and elongation of the hypoplasic maxilla. The
      aesthetic results are excellent, and the nasolabial angle is increased, including
      a more anterior projection of the upper lip. Nasal breathing is improved as well
      as the air flow and patency of the nasal airway. Velopharyngeal function remains
      unchanged after the procedure. The follow-up in this series varied from 6 months
      to 3 years. No relapses have been observed.

PMID- 9514328
TI  - A comparison of resource costs of immediate and delayed breast reconstruction.
AB  - The resource cost (cost to our hospital) of providing mastectomy plus breast
      reconstruction was calculated for 276 patients who had received both mastectomy
      and breast reconstruction at our institution. All patients had completed the
      entire reconstructive process, including reconstruction of the nipple. The
      resource costs of providing mastectomy with immediate breast reconstruction were
      compared with those of mastectomy with subsequent delayed reconstruction. We
      found that the mean resource cost for the 57 patients who had separate mastectomy
      followed by delayed breast reconstruction ($28,843) was 62 percent higher than
      that of mastectomy with immediate reconstruction ($17,801; n = 219, p < 0.001).
      Similar differences were found when patients were subgrouped by type of
      reconstruction (TRAM versus tissue expansion and implants), by laterality
      (unilateral versus bilateral), and by history of preoperative irradiation. We
      conclude that mastectomy with immediate breast reconstruction is significantly
      less expensive than mastectomy followed by delayed reconstruction and can
      potentially conserve resources.

PMID- 9514329
TI  - Free innervated latissimus dorsi muscle flap for reconstruction of full-thickness
      abdominal wall defects.
AB  - Full-thickness abdominal wall defects continue to be a challenge for the
      reconstructive surgeon. The most frequently used reconstructive techniques are
      transfer of a pedicled, local abdominal flap or a distant flap from the thigh
      region. The purpose of this paper is to present a new approach to full-thickness
      abdominal wall reconstruction using an innervated free latissimus dorsi
      musculocutaneous flap. Four patients with large full-thickness abdominal wall
      defects underwent reconstruction with a free innervated latissimus dorsi muscle
      flap. In two patients, staged abdominal wall reconstruction was performed.
      Primary closure was first obtained with a skin graft. During the subsequent
      definitive reconstruction (with an innervated free latissimus dorsi muscle flap),
      this skin graft was not excised. Instead, deep dermabrasion of the skin graft was
      performed, leaving a residual dermal layer. This layer was then covered with a
      free innervated latissimus dorsi muscle flap. In these two cases, there was no
      need for the use of a prosthetic mesh. A single stage reconstruction was
      performed in the other two cases. After abdominal wall sarcoma resection, Prolene
      mesh was placed and subsequently covered with a free innervated latissimus dorsi
      muscle flap. There were no free flap failures. The average time of surgery was 4
      hours, 50 minutes. The average hospital stay was 14 days. No significant
      complications occurred except for one donor site seroma. No hernias have occurred
      postoperatively. The mean follow-up was 21 months. Postoperatively,
      electromyographic testing was performed regularly in all patients to document
      reinnervation of the latissimus dorsi muscle flap. With reinnervation and
      intensive muscle training, the transplanted latissimus dorsi muscle offers enough
      contractile capacity and strength to adequately replace the function of the
      missing abdominal wall muscles. In complicated staged reconstructions,
      dermabrasion of the temporary skin graft allows for the use of a residual dermal
      layer as a fascia-like substitute to aid in the restoration of structural
      integrity. The combination of the dermal layer with an innervated free latissimus
      dorsi muscle provides a strong, vascularized fascial repair as well as an
      overlying vascularized soft-tissue coverage. In conclusion, adequate functional
      dynamic reconstruction of full-thickness abdominal wall defects is possible using
      an innervated free latissimus dorsi muscle flap. The reinnervated latissimus
      dorsi muscle is suitable for reconstitution of the missing functional and
      anatomic components of complex abdominal wall defects.

PMID- 9514330
TI  - Restoring abdominal wall integrity in contaminated tissue-deficient wounds using
      autologous fascia grafts.
AB  - Necrotizing abdominal wall infections, enteric fistulae, or exposed prosthetic
      material after ventral hernia repair often results in a loss of abdominal wall
      integrity. Further surgical reconstruction with prosthetic material is usually
      contraindicated in the contaminated wound because of the high infection rate
      necessitating prosthetic removal and further abdominal wall debridement.
      Consequently, for the past 9 years, we have been using free grafts of autologous
      fascia lata to replace deficient abdominal wall fascia and muscle in situations
      where prosthetic material is contraindicated and local tissue rearrangement
      (i.e., component separation) would be inadequate. Thirty-two patients (mean age
      59 years) underwent abdominal wall reconstruction with autologous fascia lata
      grafts. Indications included exposed mesh (31 percent), enteric fistulae (28
      percent), enteric contamination (22 percent), wound infection (13 percent), and
      immunosuppression alone (6 percent); 31 percent of all patients were
      immunosuppressed secondary to either a solid organ transplant or a systemic
      inflammatory disorder. Fascia grafts (mean size 10 x 17 cm) were sutured to the
      surrounding abdominal wall and covered by local skin flap advancement and/or
      myocutaneous flap rotation. All abdominal reconstructions were initially
      successful. Subsequent local abdominal wall complications included cellulitis (n
      = 3), seroma (n = 2), and skin dehiscence with exposed fascia grafts (n = 7).
      Five of seven patients with skin dehiscence healed by secondary intention,
      whereas two had split-thickness skin grafts successfully applied to the
      granulating fascia. Thigh donor site complications included hematoma (n = 1),
      skin dehiscence (n = 1), and seroma (n = 2). There have been no cases of lateral
      knee instability. The average follow-up period is 27 months (range 3 to 106
      months). Recurrent hernia has been seen in three patients (9 percent).
      Interestingly, laparotomy has been performed through an intact fascia lata patch
      in three patients for unrelated intra-abdominal conditions. In each case, the
      graft was intact and revascularized, confirming experimental animal data
      performed in our laboratory. Recurrent hernia has not been observed through the
      laparotomy site. Our 9-year experience has demonstrated that in the face of
      large, contaminated abdominal wounds where prosthetic material is contraindicated
      and local tissue rearrangement would be inadequate, fascia lata autografts are a
      reliable adjuvant to abdominal wall reconstruction.

PMID- 9514331
TI  - Perforator-based flap for coverage of lumbosacral defects.
AB  - Lumbosacral defects on 20 patients were covered with a perforator-based flap.
      Cutaneous perforators derived from the 9th and 10th intercostal arteries, the 4th
      lumbar artery, and multiple gluteal perforators that penetrate the gluteus
      maximus muscle were used as vascular pedicles. Minor complications occurred in
      five cases. Using this method, minimal morbidity of the donor site is expected
      because the gluteus maximus need not be sacrificed. Accordingly, perforator-based
      flaps are especially indicated for ambulatory patients, but for paraplegic
      patients as well. Even in the event of recurrence, another perforator-based or
      musculocutaneous flap can be elevated from the ipsilateral side because of the
      presence of multiple perforators in the lumbosacral and gluteal regions.

PMID- 9514332
TI  - Reconstruction for palmar skin defects of the digits and hand using plantar
      dermal grafting.
AB  - The plantar skin is considered suitable for skin grafting onto the volar aspect
      of the digits and hand. However, this method is not widely used because it is
      associated with problems at the donor site. To solve these problems, a new method
      was developed in which two different layers of the plantar skin are harvested
      from the same site. In this method, a split-thickness skin graft of the upper
      layer including the corneal layer of epidermis and a dermal graft of the lower
      layer are harvested from the same plantar skin. The split-thickness skin graft is
      returned to the original donor site, whereas the dermal graft is used for the
      palmar skin defects on the digits and hand. To prevent drying, the dermal graft
      was covered with a wound-covering material to achieve good graft takes.
      Reconstruction was performed for 17 patients using this method, involving digit
      only reconstruction in 8 patients, and wider reconstruction in the other 9.
      Excellent color and texture match of the graft and donor sites were obtained with
      no noticeable marginal scarring, and the durability of the skin was satisfactory.
      This method was useful for skin grafting to the digits and palms with minimal
      sacrifice to the donor site.

PMID- 9514333
TI  - Pulp reconstruction of fingers with very small sensate medial plantar free flap.
AB  - The essence in dealing with the pulp deficit accompanying fingertip injuries lies
      in functional restitution of the inherent skin texture and characteristics unique
      to that area and sufficient preservation of digital length, along with successful
      restoration of fine tactile sensation indispensable to delicate and skillful
      maneuvers. Among various techniques used to meet such demands, the very small
      sensate medial plantar free flap can be considered an excellent method in view of
      the skin texture that allows firm grasping, durability to friction rub, a cushion
      effect, and adequate sensation. Six cases of finger pulp reconstruction with the
      very small sensate medial plantar free flap are presented. At follow-up
      examination (an average follow-up of 24.3 months), the patients were evaluated
      clinically and neurologically. The operative procedures, advantages, and results
      in clinical cases are presented. Satisfactory results were obtained with
      sufficient preservation of digital length and good sensory recovery. No
      functional deficit was found at the donor site.

PMID- 9514334
TI  - The reverse digital artery island flap: clinical experience in 120 fingers.
AB  - Fingertip injuries represent the most common type of injuries seen in the upper
      extremity. Their management is functionally and aesthetically important but at
      the same time very controversial. The aim of this study is to report usefulness
      and postoperative results of reverse digital artery island flaps for fingertip
      reconstruction. From July of 1984 to December of 1995, 120 fingers in 110
      patients with defects of the distal phalanx were reconstructed by reverse digital
      artery island flaps at Korea University Guro Hospital. We reviewed the medical
      records of our cases and analyzed them in several aspects. In 21 cases,
      neurorrhaphy was performed to improve sensibility. In the majority of the cases,
      the defect was covered primarily, whereas in 27 cases it was covered secondarily
      after composite graft, replantation, and so on. All the flaps survived except for
      one. Long-term follow-up for more than 6 months was possible in 44 fingers in 41
      patients. Light touch and temperature sensation could be detected in all the
      evaluated flaps. The mean values of the static two-point discrimination test in
      sensate and insensate flaps were 6.2 and 10.2 mm, respectively. The reverse
      digital artery island flap is a safe and reliable procedure with a high survival
      rate and therefore is an excellent choice for coverage of fingertip defects.

PMID- 9514335
TI  - Distally based fasciocutaneous flaps: a versatile option for coverage of
      difficult war wounds of the foot and ankle.
AB  - Early reconstructive treatment of war-related lower extremity injuries can be
      feasible even when evacuation to ideal tertiary facilities is impossible.
      However, in such instances, lengthy procedures considered "state of the art" in
      the everyday civilian practice of plastic surgery are often impractical, and
      alternative options need to be sought. Undelayed distally based fasciocutaneous
      flaps of the leg have recently been used in 12 cases of extensive defects of the
      foot due to antipersonnel mine injuries. All patients, treated during the
      conflict in Bosnia-Herzegovina, were smokers and were between 17 and 45 years of
      age. No preoperative arteriography or Doppler was available. One flap was totally
      lost, and two others suffered tip necrosis. All other cases healed uneventfully.
      We were impressed at the reliability of distally based fasciocutaneous flaps,
      even with length-to-width ratios of up to 5:1, and even after distal
      deepithelialization or tubing of the pedicle. The whole foot can be reached when
      the appropriate lateral or medial based flap is selected. Obvious disadvantages
      are the grafted secondary defect of the leg and the lack of sensation, although
      the latter is a common feature shared by most other flaps to the foot. Also, free
      muscle transfer is preferable for very deep defects with extensive bone loss.
      However, for the ease of dissection, versatility, and short operating time,
      distally based fasciocutaneous flaps find a definite place in reconstructive
      trauma surgery.

PMID- 9514336
TI  - Prefabrication of mucosa-lined flaps: a preliminary study in the pig model.
AB  - There is a need in reconstructive surgery for flaps lined by nonkeratizing
      stratified squamous epithelium or mucous membrane. Applications could be found in
      nasal, oral, genital, and esophageal reconstruction and even in reconstruction of
      hollow intra-abdominal tubes. Prefabrication of lined flaps has so far been
      limited to a pretransfer grafting of split-thickness skin. However, in certain
      situations this does not satisfy the primary requirement of replacing "like with
      like." Also, the availability of donor sites for harvesting mucosa is limited.
      The present study involves prefabrication of mucosa-lined flaps without causing
      donor site morbidity. The study was carried out on six mini-Hartford pigs. Buccal
      mucosa was harvested from the cheeks; the sheet was divided into several smaller
      graft pieces of 1 to 2 cm2 area. These graft pieces were then applied to the deep
      fascia at a distance of 5 to 15 mm from one another, also to galea, and to the
      undersurface of skin flaps. The grafted area was isolated from the opposing
      surface with a silicone sheet or Marlex mesh. The grafts were allowed to take
      and, it was hoped, merge together to form a sheet graft of dimensions greater
      than those of the original. Two to 7 weeks after the initial grafting, the skin
      flap was elevated; the mucosal grafts were observed macroscopically for take and
      surface area and microscopically to confirm that the lining was indeed mucosa.
      The mucosa took well on both the fascia and galea and also on the undersurface of
      the skin; it enlarged in size, and the small pieces became confluent to form a
      single sheet. The increase in surface area varied from 33 percent at 11 days
      postgrafting to a maximum of 238 percent after 7 weeks. All pigs had positive
      cultures from the mucosa before implantation but only one developed gross
      infection leading to partial graft loss.

PMID- 9514337
TI  - Nerve and blood vessel growth in response to grafted dermis and cultured
      keratinocytes.
AB  - The aim of this study was to study innervation and angiogenesis in response to
      grafts of dermis and cultured keratinocytes using immunohistochemical techniques.
      In a porcine model, fresh autologous de-epidermalized dermis and cultured
      autologous keratinocytes were combined using a two-stage technique, to produce
      keratodermal grafts. Wounds were encased within skin graft chambers that
      prevented the influence of the surrounding skin. As grafts contracted, a
      peripheral rim of granulation tissue became exposed, allowing us to compare the
      wound bed beneath grafts with that beneath the raw granulating surface. Grafts
      were studied for 6 weeks. Angiogenesis was studied using antisera to von
      Willebrand factor to detect endothelial cells. Nerve growth was studied using
      antisera to S-100, a Schwann cell marker, and to four axonal markers: protein
      gene product 9.5, C-flanking peptide of neuropeptide Y, calcitonin gene-related
      peptide, and vasoactive intestinal peptide. In kerato-dermal grafts (n = 28),
      organization of blood vessels and nerve growth occurred only beneath areas with
      epidermal cover as compared with the surrounding granulation tissue. Initially,
      the immunoreactivity to von Willebrand factor was high, but in areas with
      epidermal cover it assumed a more orderly pattern with fewer blood vessels.
      Innervation was first detected by S-100 immunoreactivity seen at 1 to 2 weeks,
      closely followed by that to protein gene product 9.5 and much later to calcitonin
      gene-related peptide. C-flanking peptide of neuropeptide Y and vasoactive
      intestinal peptide immunoreactivity were detected in the wound depth surrounding
      large blood vessels at 4 to 6 weeks. In control wounds that had been either
      grafted with de-epidermalized dermis alone (n = 10) or allowed to granulate (n =
      10), persistently there was high immunoreactivity to von Willebrand factor but
      minimal immunoreactivity to the neural markers. In conclusion, kerato-dermal
      grafts become innervated, and beneath their surface there is also vascular
      organization to resemble normal skin. Keratinocytes themselves may influence
      angiogenesis and innervation, as both processes failed to occur beneath
      granulating areas.

PMID- 9514339
TI  - Surgical treatment of a patient with obstructive sleep apnea syndrome associated
      with temporomandibular joint destruction by rheumatoid arthritis.

PMID- 9514338
TI  - Rat tibial nerve regeneration after postoperative administration of cis
      diaminedichloroplatinum.
AB  - We investigated the results of postoperative administration of cis
      diaminedichloroplatinum on nerve regeneration in rats. Forty-two Lewis rats were
      divided into two groups, receiving end-to-end suture or nerve grafting. Subgroups
      of the suture group included control, a one-time dose of cis
      diaminedichloroplatinum (3 mg/kg), and four doses of the same amount of cis
      diaminedichloroplatinum. Subgroups in the nerve grafting group included a control
      and a four-dose group. Functional recovery was measured by gait analysis using
      the tibial function index. Biopsies of nerve were taken distal to the suture site
      for histologic evaluation 20 weeks postoperatively. Tibial function index at 4,
      6, and 20 postoperative weeks in the four-dose group was significantly inferior
      to that of the control group in the suture group. Tibial function index was
      inferior in the four-dose group until 10 weeks postoperatively compared with
      control in the nerve grafting group; however, there was no significant
      difference. The percentage of neural tissue in the one-dose suture group was
      significantly greater than in the four-dose suture group. These results suggest
      that postoperative cis-diaminedichloroplatinum administration may have a
      detrimental effect on nerve regeneration.

PMID- 9514340
TI  - A supportive technique using a splint to obtain definite contour and desirable
      protrusion after reconstruction of microtia.

PMID- 9514341
TI  - A new application for reconstruction of areola with transplantation of cultured
      autologous melanocytes.

PMID- 9514343
TI  - Reconstruction of a large anterolateral knee defect using a delayed distally
      based total sartorius flap and a medial gastrocnemius flap.

PMID- 9514342
TI  - Three-dimensional computed tomography reconstruction of the carpal tunnel and
      carpal bones.

PMID- 9514344
TI  - The subcutaneous laterodigital reverse flap.

PMID- 9514345
TI  - In pursuit of optimal rejuvenation of the forehead: endoscopic brow lift with
      simultaneous carbon dioxide laser resurfacing.
AB  - Coronal foreheadplasty has long been the traditional method of improving the
      aesthetic appearance of the forehead, permitting not only repositioning of ptotic
      tissues but also direct access for modification of the "frown" muscles. However,
      it was only moderately successful in eliminating vertical corrugator lines or
      deeply etched transverse wrinkles. The recent advent of the endoscopic brow lift
      has permitted us to minimize the dysesthesias associated with the coronal
      approach by making the incisions shorter and radially oriented and by being more
      precise in the muscle resection. Nonetheless, endoscopic brow lift gives no
      further improvement in persistent deep vertical and transverse wrinkles. Carbon
      dioxide laser resurfacing can improve the existing wrinkles but does not
      eliminate the muscular cause of forehead wrinkles. It seemed reasonable that
      combining these techniques might yield better results than either procedure
      alone. To evaluate this possibility, 30 patients with simultaneous endoscopic
      brow lift and carbon dioxide resurfacing were compared with 24 patients having
      laser resurfacing only and with 26 patients who had traditional coronal
      foreheadplasty. Both foreheadplasty groups had corrugator resection. All patients
      were evaluated at least 4 to 6 months postoperatively. Ratings were based on the
      percent of wrinkles removed, both vertical and transverse. The ratings were
      performed with predetermined criteria by a surgeon not involved with the
      operative procedures nor after care. A rating of "excellent" (> or = 95 percent
      reduction in wrinkles) was obtained in 50 percent of coronal foreheadplasties;
      41.7 percent of carbon dioxide resurfacing alone and 80 percent of endobrow lifts
      with carbon dioxide laser resurfacing. There was no vascular compromise from this
      latter combination of procedures, no hypertrophic scars, and no impairment of
      healing. We conclude that endoscopic brow lift with carbon dioxide laser
      resurfacing is a safe and perhaps more effective means of aesthetic rejuvenation
      of the forehead.

PMID- 9514346
TI  - Breast capsule persistence after breast implant removal.
AB  - Breast implant capsules are a foreign body immune response to breast implants. It
      has been proposed that capsulectomy after breast implant removal was unnecessary,
      as the body resorbs the capsule when the implant, the impetus for the foreign
      body response, is removed. We report eight women with persistent capsules 10
      months to 17 years after silicone breast implant removal.

PMID- 9514347
TI  - Extending the role of liposuction in body contouring with ultrasound-assisted
      liposuction.
AB  - The initial experience with ultrasound-assisted liposuction in treating difficult
      fibrous areas, such as gynecomastia, hitherto not uniformly responsive to
      traditional suction-assisted lipoplasty, has led to the evolution and improvement
      of ultrasound-assisted liposuction techniques. This prospective study examined
      114 consecutive patients treated with ultrasound-assisted liposuction over a 13
      month period, from September of 1996 to September of 1997. The means by which
      this procedure helps achieve fat contouring differs from that of suction-assisted
      lipoplasty. Ultrasound-assisted liposuction removes fat through a fat
      emulsification process termed "cavitation," whereas suction-assisted lipoplasty
      achieves contouring through the mechanical avulsion of fat. The technique for the
      use of ultrasound-assisted liposuction has changed significantly from our initial
      series of patients to our current technique. To optimize the benefits of both
      ultrasound-assisted and traditional suction-assisted lipoplasty, we use a three
      stage technique consisting of infiltration, ultrasound-assisted sculpturing, and
      suction-assisted lipoplasty for evacuation and final contouring. This has
      decreased our operative time, minimized complications, and optimized our body
      contouring results. Data were collected intraoperatively, including treatment
      times, treatment volumes, and treatment areas for both suction-assisted and
      ultrasound-assisted lipoplasty. A total of 114 patients were treated with
      ultrasound-assisted liposuction between September of 1996 and September of 1997.
      There were 23 male patients and 91 female patients. In general, the average total
      volume removed with this procedure decreased by about 50 percent throughout the
      series, whereas the suction-assisted lipoplasty volume increased correspondingly
      by 50 percent. Overall, suction-assisted lipoplasty volume was approximately two
      times ultrasound-assisted liposuction volume in the same area. Exceptions to this
      include the dense fibrous areas such as the back and male breast, where
      aspiration volumes were approximately equal. The total ultrasound-assisted
      liposuction treatment times were reduced after our initial 30 patients, and
      suction-assisted lipoplasty times increased. Total aspiration rates in our later
      patients averaged 36.2 cc/per minute for ultrasound-assisted and 58.4 cc/per
      minute for suction-assisted lipoplasty, whose rates were approximately 1.5 to 2
      times faster than for ultrasound-assisted liposuction in most areas. After using
      this technology in our initial series of 30 patients, it became apparent that
      ultrasound was not a substitute for suction-assisted lipoplasty but rather a
      natural complement. We have found that the marriage of the techniques enhances
      results and minimizes complications, such as seromas, which have been reported to
      be 11.4 percent with ultrasound-assisted liposuction alone and are 2.6 percent in
      our series.

PMID- 9514348
TI  - Personal experience with ultrasound-assisted lipoplasty: a pilot study comparing
      ultrasound-assisted lipoplasty with traditional lipoplasty.
AB  - Body contouring with traditional suction-assisted lipoplasty is currently the
      most commonly performed aesthetic surgical procedure. In competent hands,
      traditional lipoplasty has a low complication rate, a short recovery period, and
      a high patient satisfaction rate. Body contouring with ultrasound-assisted
      lipoplasty has recently gained considerable attention, and its proponents have
      claimed many benefits over the traditional method. This pilot study consists of
      one surgeon's clinical experience with ultrasound-assisted lipoplasty in 100
      cases. In 63 of these patients, ipsilateral traditional lipoplasty and
      contralateral ultrasound-assisted lipoplasty were done on one or more body areas.
      These patients were blinded in the study. Complication rates, lipocrits from the
      aspirate, postoperative ecchymosis, postoperative swelling, patient satisfaction,
      and surgeon satisfaction were then compared for each patient studied. Ten
      randomly selected patients were also evaluated by an independent panel of
      reviewers who compared ecchymosis and swelling in ultrasound-assisted versus
      traditional lipoplasty-treated areas. Their observations in this subset of 10
      patients were subjected to statistical analysis. This initial pilot study failed
      to prove most of the benefits attributed to ultrasound-assisted lipoplasty by
      other surgeons. However, the method is an evolving technology, and the authors
      remain optimistic about the role of ultrasound in body sculpting surgery.

PMID- 9514349
TI  - The flaring suture to augment the repair of the dysfunctional nasal valve.

PMID- 9514350
TI  - If we are not plastic surgeons, who are we?

PMID- 9514351
TI  - Genetics of limb development and congenital hand malformations.
AB  - The vertebrate limb bud develops along three different axes: proximodistal,
      anteroposterior, and dorsoventral. Several genetic factors responsible for
      control of each of the three limb axes have been identified. The genes involved
      interact in complex feedback loops to achieve proper arrangement and
      differentiation of tissues. Most of the available information on limb development
      and patterning has come from studies carried out in the lower vertebrates. In
      recent years, an increasing number of studies have been unraveling the genetic
      basis of human hand malformation phenotypes. At present, genes responsible for
      preaxial polydactyly, split hand/split foot malformation, and brachydactyly type
      C have been localized, and the gene responsible for synpolydactyly has been
      identified. In this paper, we present an overview of the genetic factors involved
      in limb development, followed by summarized discoveries in the genetics of human
      congenital hand malformations.

PMID- 9514352
TI  - Psychological investigations in cosmetic surgery: a look back and a look ahead.
AB  - This article reviews the history of psychological investigations of cosmetic
      surgery patients. These studies have been designed to address two fundamental
      questions: (1) Are there "patient types" or forms of psychopathology that serve
      as contraindications to cosmetic surgery? and (2) What is the likelihood of
      psychological change following cosmetic surgery? This review suggests that the
      research has not fully answered these questions. In response, we propose a new
      direction for psychological investigation, focusing on issues of body image in
      cosmetic surgery patients. We discuss the relationship between body image and
      cosmetic surgery and pose several relevant questions for future research.

PMID- 9514353
TI  - Late arterial insufficiency in a toe-to-finger transplantation following
      infiltration anesthesia with articaine plus epinephrine during septorhinoplasty.

PMID- 9514355
TI  - Documentary improvement after endoscopic facial surgery.

PMID- 9514354
TI  - A simple technique for correction of mucosal irregularities of the lip.

PMID- 9514356
TI  - The ligamentous facial fence: the cause of nasolabial folds and jowling.

PMID- 9514357
TI  - Detection of titanium in human tissues after craniofacial surgery.

PMID- 9514358
TI  - Pedicle modification of the Lejour vertical scar reduction mammaplasty.

PMID- 9514359
TI  - MRI interaction with tattoo pigments.

PMID- 9514360
TI  - Carpal tunnel release with short incision.

PMID- 9514361
TI  - The regulation of adhesion molecules in muscle flaps exposed to ischemia
      reperfusion injury.

PMID- 9514362
TI  - The temporalis muscle flap revisited on its centennial: advantages, newer uses,
      and disadvantages.

PMID- 9514363
TI  - The importance of vascular territories in designing new experimental skin flaps.

PMID- 9514364
TI  - The gluteus maximus V-Y advancement flap.

PMID- 9514365
TI  - Posttraumatic lipoma.

PMID- 9514366
TI  - Missed closed degloving injuries: late presentation as a contour deformity.

PMID- 9514367
TI  - Closing a wide wound by using two stout spinal needles and three Allis forceps.

PMID- 9514368
TI  - Platelet gel as an intraoperatively procured platelet-based alternative to fibrin
      glue.

PMID- 9514369
TI  - Failure of silicone gel breast implants: analysis of literature data for 1652
      explanted prostheses.

PMID- 9514370
TI  - Association of dehydroepiandrosterone sulfate, body composition, and physical
      fitness in independent community-dwelling older men and women.
AB  - OBJECTIVES: To determine the association of dehydroepiandrosterone sulfate
      (DHEAS), body composition, and physical fitness in independent community-dwelling
      men and women aged 60 to 80 years. DESIGN: Cross sectional analysis.
      PARTICIPANTS: Independent men and women, 60 years of age and older, living in
      urban and suburban communities of Southeastern Wisconsin. MEASUREMENTS: History,
      physical examination, physical activity level, and anthropometrics were measured
      for every subject. Total adipose mass (TAM) and lean body mass were measured
      using dual energy X-ray absorptiometry. Dehydroepiandrosterone sulfate, insulin
      like growth factor-1 (IGF-1), total testosterone (TT), and free testosterone (FT)
      were measured using radioimmunoassay. Physical fitness was measured as VO2max
      using exercise stress tests. Blood for lipids was analyzed using standard assays.
      RESULTS: In men, the DHEAS was significantly correlated to age (r = -.32), TAM (r
      = -.27), percent fat (r = -.30), HDL cholesterol (r = .34), TT (r = .30), VO2max
      (r = .23), and percent lean body mass (% LBM) (r = .33). In women, the DHEAS was
      not significantly correlated to any of the variables examined except body mass
      index (BMI) (r = .23). In men, after partialling out age, DHEAS was significantly
      correlated to HDL, % fat, TAM, % LBM, and TT. Multivariate analysis for men
      revealed that high density lipoprotein cholesterol (HDL) was the strongest
      predictor of serum DHEAS level, followed by % LBM, BMI, and age. The men in the
      highest quartile of serum DHEAS levels were different from those in the lowest
      quartile in terms of age, TT, FT, % fat, TAM, % LBM, HDL, and low density
      lipoprotein (LDL) cholesterol level. No such differences were found in the two
      groups of women. CONCLUSION: In this group of independent community-dwelling
      older men, several factors were found to be associated with the serum DHEAS
      concentration, whereas in a group of older women, no such associations were
      identified with the exception of BMI. Men in the highest quartile of serum DHEAS
      level, compared with those with a serum DHEAS level in the lowest quartile, were
      younger, leaner, more fit, had higher TT and FT levels, and had a favorable lipid
      profile. No such differences were identified between the women in the highest and
      the lowest quartiles of serum DHEAS level.

PMID- 9514371
TI  - Strength, physical activity, and body mass index: relationship to performance
      based measures and activities of daily living among older Japanese women in
      Hawaii.
AB  - OBJECTIVES: Remaining strong, lean, and physically active may contribute to
      successful aging, both by maintaining function and by enabling more independent
      living. The study objective was to investigate this hypothesis among a long-lived
      population of older Japanese women. DESIGN: A cross-sectional study. SETTING: The
      island of Oahu, Hawaii. PARTICIPANTS: A total of 705 community-dwelling women
      (mean age, 74; range, 55-93). MEASUREMENTS: As outcomes, 7 physical performance
      measures including walking speed, the Get Up and Go test, chair stands,
      functional reach, and hand and foot reaction times, and 8 questions regarding
      activities of daily living (ADL). As possible predictors, physical activity, body
      mass index, and quadriceps, grip, and triceps strength. RESULTS: In multivariable
      models, one or more of the strength tests was associated positively with six of
      the seven performance-based measures. Among the significant associations, 1-SD
      increases in strength were associated with 2 to 4% increases in performance
      compared with the sample mean. Physical activity was independently, and
      positively associated with the most complex of the tests, the Get Up and Go test.
      Body mass index (BMI), in contrast to strength and physical activity, was
      negatively associated with five of the seven performance tests. Among the
      significant associations, 1-SD increases in BMI were associated with 3 to 8%
      reductions in performance. In multivariable models strength was also associated
      positively with seven of the eight ADLs. In the same models, physical activity
      was positively associated with five and BMI was negatively associated with six of
      the ADLs. CONCLUSION: The results suggest that remaining strong, lean, and
      physically active provided wide-ranging benefits for this population of older
      Japanese women.

PMID- 9514372
TI  - Ethnicity and decision-makers in a group of frail older people.
AB  - OBJECTIVE: To assess the relationship between ethnicity and decision-makers
      expressing healthcare wishes in a group of frail older persons enrolled in the
      Program of All-inclusive Care for the Elderly (PACE). DESIGN: A retrospective
      chart review of 1193 participants in the PACE program. SETTING: Program of All
      inclusive Care for the Elderly, a comprehensive managed care demonstration
      program serving frail older participants at 10 sites across the nation.
      PARTICIPANTS: A total of 1193 older adults, all of whom met state criteria for
      nursing home level of care. Three hundred were non-Hispanic whites, 364 were
      black, 156 were Hispanic, and 288 were Asian. MEASUREMENTS: Demographic
      characteristics of the patients and the presence or absence of an alternative
      decision-maker; the characteristics of alternative decision-makers included the
      relationship to the participant as recorded in the patient's medical record.
      RESULTS: Ninety-one percent of white patients expressed their own healthcare
      wishes in contrast to only 85% of Hispanic, 83% of Asian, and 67% of black
      patients. An alternative decision-maker was identified for about 15% of Asians
      and Hispanics and for one-third of blacks, but only about 8% of whites had an
      alternative decision-maker. Black and Hispanic patients were most likely to have
      a daughter as an alternative decision-maker, Asians were most likely to have a
      son, and whites patients were most likely to have a spouse as an alternative
      decision-maker. Blacks, particularly black men, were the most likely to have a
      relative other than a spouse or child as an alternative decision-maker.
      CONCLUSIONS: In this population, we found significant ethnic variation in the
      person identified to be the decision-maker in a group of frail older people.
      Ethnic variation reflected sociodemographic as well as cultural differences.
      However, there are important limitations to this study, and caution should be
      used in extrapolating the results to other populations or in attributing the
      results to ethnicity alone. An awareness of cross-cultural patterns in identified
      or de facto decision-makers can be significant for healthcare workers when they
      approach patients and their families about issues surrounding end of life
      decisions.

PMID- 9514373
TI  - Barriers to obtaining consent in dementia research: implications for surrogate
      decision-making.
AB  - OBJECTIVE: To identify barriers to informed consent in research involving
      subjects with advanced dementia. DESIGN: A randomized controlled clinical trial
      of palliative care approaches, compared with usual care, in subjects with
      advanced dementia who are hospitalized. SETTING: A large metropolitan teaching
      hospital. PARTICIPANTS: All patients older than 65 years of age who have advanced
      dementia and a Functional Assessment Staging score of 6d to 7f and have been
      admitted to the hospital. MEASUREMENTS: Surrogates for all eligible subjects were
      approached for consent to enroll their family members in the trial. Reasons for
      refusal to enroll in the study were recorded and categorized as either informed
      refusal (i.e., the surrogate understood the research protocol but declined to
      give consent for participation) or as a barrier to informed consent (i.e., the
      surrogates could not participate in the informed consent process or there was no
      functional surrogate). RESULTS: Forty-nine percent of 146 eligible subjects could
      not be enrolled in the study. Only four surrogates refused consent for their
      family members. Of the remaining 68 patients, 41 eligible subjects' surrogates
      could not be engaged in the informed consent process, and 22 subjects did not
      have a functional surrogate to consent for research. CONCLUSIONS: Absence of
      functional surrogate decision-makers is a major barrier to research and clinical
      decision-making for hospitalized patients with advanced dementia.

PMID- 9514374
TI  - Exploring joint research initiatives: opportunities for collaboration between the
      US and the UK.

PMID- 9514375
TI  - Outpatient geriatric evaluation and management.
AB  - OBJECTIVE: To describe the development and operation of a practical model of
      outpatient geriatric evaluation and management (GEM) for high-risk, community
      dwelling older adults. PARTICIPANTS: Community-dwelling Medicare beneficiaries
      age 70 years and older who were medically stable but had a high probability of
      repeated admission to hospitals (P(ra) > .40) in the future (n = 248).
      INTERVENTION: Outpatient GEM. MEASUREMENTS: Demographic, clinical, and use-of
      hospital characteristics of patients; nature and quantity of GEM services;
      satisfaction of patients and their established primary physicians. RESULTS: At
      enrollment, the average patient was 78.7 years old, took 5.0 long-term
      prescription medications and was unable to perform 0.5 (of six) activities of
      daily living (ADL) and 1.4 (of seven) instrumental ADL. Many patients (71.3%)
      reported hospital days during the previous year. Each of three interdisciplinary
      teams (geriatrician, gerontological nurse practitioner, nurse and social worker)
      performed comprehensive assessments and then provided primary care and case
      management to a case load of 45 to 52 patients. On average, GEM required 6
      months, during which patients visited the GEM clinic 7.4 times, had 10.4 active
      problems addressed, spoke to GEM staff members weekly by telephone, and were
      referred to two other providers. Most patients (94.4%) completed the GEM program;
      66.7% completed advance directives. Satisfaction with GEM was high among the
      patients and their established primary physicians. The cost of the GEM personnel
      averaged about $1540 per patient treated. CONCLUSIONS: This model of outpatient
      GEM provided 6 months of targeted intensive care at a reasonable cost. The
      satisfaction ratings of patients and their primary physicians were high.

PMID- 9514376
TI  - Essential components of geriatric care provided through health maintenance
      organizations. The HMO Workgroup on Care Management.
AB  - The rapid growth in the number of older adults enrolling in health maintenance
      organizations (HMO) presents a number of opportunities and challenges. Older HMO
      enrollees have needs that differ from those of younger enrollees, such as the
      medical conditions they face, their likelihood of having functional deficits, and
      differences in their living arrangements. In addition, their health-related needs
      often extend beyond medical care and may include relationships with families,
      caregivers, and community agencies. This article describes the types of services
      that should realistically be available to older adults who are enrolled in an HMO
      with a Medicare risk contract in order to meet the goals of geriatric care: to
      promote health, independence, and optimal functioning, to prevent avoidable
      decline in health status, and to enhance quality of life. The findings are based
      on deliberations during the past year by the HMO Workgroup on Care Management,
      which was convened under the auspices of The Robert Wood Johnson Foundation's
      national program, "Chronic Care Initiatives in HMOs."

PMID- 9514377
TI  - The ethics of managed care: report on a Congress of Clinical Societies.

PMID- 9514378
TI  - Managed care: the third reorganization of health care.

PMID- 9514379
TI  - The future of the doctor-payer-patient relationship.

PMID- 9514380
TI  - Capitated risk-bearing managed care systems could improve end-of-life care.
AB  - Capitated or salaried managed care systems offer an important opportunity to
      provide high quality, cost-effective end-of-life care. However, capitated
      healthcare delivery systems have strong incentives to avoid patient populations
      in need of such care. Care currently provided at the end of life in fee-for
      service practice is commonly deficient, with high rates of avoidable pain and
      other burdens. Only hospice offers a better track record, yet access to hospice
      is limited, and length of stay is short. Traditional staff- or group-model
      managed care plans, with their emphasis on prevention, patient education, cost
      efficiency, service coordination, and integrated provider networks, present a
      dynamic set of conditions and organizational structures that would support real
      change. Advantages derived from managed care systems providing quality end-of
      life care include coordinated care across delivery sites, interdisciplinary
      teams, integrated services, and opportunities to develop innovative care
      programs, service arrays, utilization controls, and accountability for care
      standards. We propose a special comprehensive system of managed care, which we
      call MediCaring, for seriously ill persons nearing the end of life. MediCaring
      would encompass the best elements of palliative care within a managed care
      structure: comprehensive, supportive, community-based services that meet personal
      and medical needs, a focus on patient preferences, symptom management, family
      counseling, and support. Other programs, such as hospice, have shown that
      continuity and coordinated care, financed through a capitated payment and
      directed at a special population, are both feasible and effective. There are
      obstacles to improving care at the end of life. Managed care systems, like most
      of medical care, have largely ignored the terminally ill patient. Current
      financing arrangements make it financially undesirable for insurers to recruit or
      retain the very sick; very ill patients can be costly over a prolonged time. In
      addition, inertia and habit inhibit change, and there are few criteria by which
      to judge whether care at the end-of-life is "good." Nevertheless, capitated or
      salaried managed care systems committed to enhanced end-of-life care seem well
      positioned to achieve it if payment reimbursements were revised to encourage this
      end.

PMID- 9514381
TI  - Revenue streams and clinical discretion.

PMID- 9514382
TI  - Conflicts of interest and accountability in managed care: the aging of medical
      ethics.

PMID- 9514383
TI  - When the benefit is in doubt, who decides?

PMID- 9514384
TI  - Drug benefits in managed care: seeking ethical guidance from the formulary?

PMID- 9514386
TI  - Letting the patient backstage: informed consent for HMO enrollees.

PMID- 9514385
TI  - Closure, fair procedures, and setting limits within managed care organizations.

PMID- 9514387
TI  - Mediation and managed care.
AB  - Managed care has not only intensified existing conflicts between patient and
      provider, it has, by its very nature, changed the shape and scope of the
      healthcare enterprise and introduced an entirely new set of disputes. The
      decision-making dynamics have been altered, and the cast of players has expanded.
      Traditionally, the therapeutic interaction took place between the physician and
      the patient although it occasionally included the patient's family. Whatever
      obligations existed, such as fidelity, confidentiality, and standard of care,
      they bound only those parties. Now, as the managed care organization has
      interposed itself between the patient and the physician, the dyad has become a
      triad. The power balance has shifted, and a new set of rights and
      responsibilities now flows between and among the players, each of whom has
      interests that may or may not coincide. This article argues that, because of its
      cost containment origins and orientation, managed care increases the likelihood
      that misunderstandings, disagreements and disputes will develop into full-blown
      conflicts. If managed care is to succeed financially and operate with integrity,
      it must develop techniques for managing the increasing conflicts that arise
      inevitably between and among the organizations, physicians, and patients. It is
      clear that the voice of the patient needs to be strengthened within the new
      complex decision-making, review, and appeal procedures. Mediation is the most
      appropriate method of dispute resolution for the managed care setting because it
      balances the disparities in power endemic to the bureaucratization of medicine
      and refocuses the interests of the various parties. Using bioethics consultation
      as a model for dispute mediation provides a set of principles and guideline tasks
      that can be applied effectively to managed care.

PMID- 9514388
TI  - A medical trust fund for managed care: the legacy of Hughley vs Rocky Mountain
      Health Care Maintenance Organization.

PMID- 9514389
TI  - Practice guidelines: a limited role in resolving rationing decisions.

PMID- 9514390
TI  - Clinical responsibility and legal liability in managed care.

PMID- 9514391
TI  - Obligations and opportunities: the role of clinical societies in the ethics of
      managed care.

PMID- 9514392
TI  - Medical education and managed care: keeping pace.

PMID- 9514393
TI  - Managed care and the goals of medicine.
AB  - The goals of medicine encompass the relief of pain and suffering, the promotion
      of health and the prevention of disease, the forestalling of death and the
      promoting of a peaceful death, and the cure of disease when possible and the care
      of those who can not be cured. Managed care, as a system of integrated healthcare
      delivery designed to control costs, is not, in principle, incompatible with the
      goals of medicine, but in practice it may well be, depending on whether profit is
      sought, whether the integrity of physicians' medical judgment is protected, and
      whether government regulations control managed care practices to prevent abuse
      and to enhance the quality of care.

PMID- 9514394
TI  - Managed care, managing ethics.

PMID- 9514395
TI  - DHEA: elixir of youth or mirror of age?

PMID- 9514396
TI  - Primary care.

PMID- 9514397
TI  - Survival of bed-ridden older patients.

PMID- 9514398
TI  - A practical psychometric approach to detect preclinical stage of dementia.

PMID- 9514399
TI  - Clinical criteria versus DNA diagnosis in heterozygous familial
      hypercholesterolemia: Is molecular diagnosis superior to clinical diagnosis?

PMID- 9514400
TI  - Smooth muscle cell heterogeneity: patterns of gene expression in vascular smooth
      muscle cells in vitro and in vivo.
AB  - Early morphological and biochemical studies indicated that vascular smooth muscle
      cells (VSMCs) exhibited two distinct phenotypes and that a change from the
      contractile to the synthetic phenotype was a prerequisite for progression of
      vascular disease. More recently, it has become evident that these phenotypes
      probably represent the extremes of a spectrum of phenotypes that may coexist in
      the vessel wall, which are dictated by their environment and functional
      requirements and which reflect differing patterns of gene expression. Therefore,
      knowledge of the key factors that regulate these patterns of gene expression is
      likely to lead to the ability to manipulate VSMC phenotype. However, before such
      factors can be identified, the relationship between VSMC gene expression and VSMC
      phenotype must first be established. We therefore undertook a differential screen
      of cDNA from VSMCs in vitro to provide a bank of gene markers that could be used
      under a variety of circumstances to define VSMC phenotype in terms of the pattern
      of genes expressed. Using this approach, we have found that the pattern of gene
      expression that occurs during neointima formation in the balloon-injured rat
      carotid artery is very similar to that seen at a specific period in the
      developing aorta of the early neonate and is characterized by coexpression of
      genes for both contractile and matrix proteins. Furthermore, recent studies have
      shown that VSMCs isolated at different stages of aortic development can stably
      maintain different phenotypic characteristics in cell culture. The use of these
      cells in transfection experiments with SM-specific promoter-chloramphenicol
      acetyltransferase reporter constructs may enable us to determine what regulates
      the pattern of gene expression in different VSMC phenotypes. Such studies may
      ultimately lead to the identification of transcription factors responsible for
      determining VSMC phenotype and may therefore provide targets for therapy aimed at
      manipulating VSMC gene expression in vascular disease.

PMID- 9514401
TI  - Herpesvirus in atherosclerosis and thrombosis: etiologic agents or ubiquitous
      bystanders?
AB  - The role of herpesvirus infections in the pathogenesis of vascular diseases
      remains an enigma. Although there is abundant circumstantial evidence of a role
      for herpesviruses in atherosclerosis and related processes, a cause-and-effect
      relationship has yet to be definitively established. This article will review the
      pathological, molecular, and biochemical evidence supporting the hypothesis that
      herpesviruses are involved in the development of atherosclerosis, restenosis
      after coronary angioplasty, accelerated atherosclerosis in recipients of heart
      transplants, and the induction of a prothrombotic phenotype in vascular
      endothelial cells.

PMID- 9514402
TI  - Regulation of PDGF-B in endothelial cells exposed to cyclic strain.
AB  - The present study was designed to examine the regulation by cyclic strain of
      endothelial cell (EC) platelet-derived growth factor-B chain (PDGF-B) expression.
      We demonstrate in this study that bovine aortic ECs subjected to 10% (but not 6%)
      average strain resulted in a 2.6-fold increase in PDGF-B steady state mRNA and
      immunoreactive protein. Nuclear runoff transcription assays confirmed the
      induction of PDGF-B transcripts. To address the regulation of PDGF-B gene
      expression by cyclic strain, we transfected bovine aortic ECs with a construct
      containing 450 bp of human PDGF-B promoter sequence coupled to chloramphenicol
      acetyltransferase (CAT), and found that subjecting these cells to 10% average
      strain resulted in a twofold increase in CAT activity by 4 hours. Analysis of
      nested 5' deletions of the promoter transfected into ECs demonstrated a 55% drop
      off in activity between position -313 and -153, with no induction of activity
      with the - 101-bp minimal promoter. Since a shear stress response element (SSRE)
      is located at position -125, we tested the hypothesis that the SSRE site was
      necessary and/or sufficient for induction of PDGF-B activity with strain.
      Electromobility shift assays revealed that nuclear proteins from ECs exposed to
      strain for short intervals (30 minutes) bound to the PDGF-B SSRE. However,
      transfection of ECs with hybrid promoter constructs containing the SV40 sequence
      promoter downstream of the SSRE or the -153 PDGF-B promoter sequence bearing a
      mutation in the SSRE demonstrated that the SSRE was not necessary for inducible
      reporter gene expression in ECs exposed to cyclic strain.

PMID- 9514403
TI  - Vitamin supplementation reduces blood homocysteine levels: a controlled trial in
      patients with venous thrombosis and healthy volunteers.
AB  - Hyperhomocysteinemia is a risk factor for atherosclerosis and thrombosis and is
      inversely related to plasma folate and vitamin B12 levels. We assessed the
      effects of vitamin supplementation on plasma homocysteine levels in 89 patients
      with a history of recurrent venous thrombosis and 227 healthy volunteers.
      Patients and hyperhomocysteinemic (homocysteine level >16 micromol/L) volunteers
      were randomized to placebo or high-dose multivitamin supplements containing 5 mg
      folic acid, 0.4 mg hydroxycobalamin, and 50 mg pyridoxine. A subgroup of
      volunteers without hyperhomocysteinemia was also randomized into three additional
      regimens of 5 mg folic acid, 0.5 mg folic acid, or 0.4 mg hydroxycobalamin.
      Before and after the intervention period, blood samples were taken for
      measurements of homocysteine, folate, cobalamin, and pyridoxal-5'-phosphate
      levels. Supplementation with high-dose multivitamin preparations normalized
      plasma homocysteine levels (< or = 16 micromol/L) in 26 of 30 individuals
      compared with 7 of 30 in the placebo group. Also in normohomocysteinemic
      subjects, multivitamin supplementation strongly reduced homocysteine levels
      (median reduction, 30%; range, -22% to 55%). In this subgroup the effect of folic
      acid alone was similar to that of multivitamin: median reduction, 26%; range, -2%
      to 52% for 5 mg folic acid and 25%; range, -54% to 40% for 0.5 mg folic acid.
      Cobalamin supplementation had only a slight effect on homocysteine lowering
      (median reduction, 10%; range, -21% to 41%). Our study shows that combined
      vitamin supplementation reduces homocysteine levels effectively in patients with
      venous thrombosis and in healthy volunteers, either with or without
      hyperhomocysteinemia. Even supplementation with 0.5 mg of folic acid led to a
      substantial reduction of blood homocysteine levels.

PMID- 9514404
TI  - Physical activity status and adverse age-related differences in coagulation and
      fibrinolytic factors in women.
AB  - Adverse changes in coagulation and fibrinolytic factors are thought to contribute
      to the increased risk of cardiovascular disease and atherothrombosis with age. We
      tested the hypothesis that such age-related changes in specific coagulation and
      fibrinolytic factors are absent in physically active women. Resting levels of
      plasma fibrinogen, tissue-type plasminogen activator (t-PA) antigen and activity,
      plasminogen activator inhibitor-1 (PAI-1) antigen and activity, and fibrin D
      dimer were measured in 24 healthy premenopausal women: 11 sedentary (aged 28+/-1
      years; Pre-S) and 13 physically active (aged 30+/-1 years; Pre-PA) and in 27
      healthy postmenopausal women: 14 sedentary (aged 61+/-1 years; Post-S) and 13
      physically active (aged 58+/-1 years; Post-PA). Post-S had higher (P<.05)
      fibrinogen, t-PA antigen, PAI-1 antigen, PAI-1 activity, and fibrin D-dimer
      levels and lower t-PA activity than Pre-S. Post-PA demonstrated lower (P<.01)
      plasma fibrinogen, t-PA antigen, PAI-1 antigen, and PAI-1 activity and higher
      (P<.01) t-PA activity levels than Post-S. In addition, plasma fibrin D-dimer
      levels tended (P=.06) to be lower in Post-PA than in Post-S. Although plasma
      levels of fibrinogen and fibrin D-dimer in Post-PA were lower than in Post-S,
      they were higher (P<.05) than in Pre-PA. Importantly, however, the fibrinolytic
      profile of Post-PA did not differ from that of Pre-PA. The results of the present
      study demonstrate that the adverse age-associated differences in plasma
      fibrinogen concentrations and the endogenous fibrinolytic system in sedentary
      healthy women are either attenuated or absent in highly physically active women.
      The smaller or absent age-related differences in coagulation and fibrinolytic
      factors in women who habitually exercise may represent an important mechanism
      contributing to their lower age-related increase in both cardiovascular disease
      and atherothrombotic events. Future studies need to determine whether women who
      are moderately active would demonstrate the same favorable hemostatic profile.

PMID- 9514405
TI  - Immunohistochemical demonstration of enzymatically modified human LDL and its
      colocalization with the terminal complement complex in the early atherosclerotic
      lesion.
AB  - Treatment of low density lipoprotein (LDL) with degrading enzymes transforms the
      molecule to a moiety that is micromorphologically indistinguishable from
      lipoproteinaceous particles that are present in atherosclerotic plaques, and
      enzymatically modified LDL (E-LDL), but not oxidized LDL (ox-LDL), spontaneously
      activates the alternative complement pathway, as do lesion lipoprotein
      derivatives. Furthermore, because E-LDL is a potent inducer of macrophage foam
      cell formation, we propose that enzymatic degradation may be the key process that
      renders LDL atherogenic. In this article, we report the production of two murine
      monoclonal antibodies recognizing cryptic epitopes in human apolipoprotein B that
      become exposed after enzymatic attack on LDL. One antibody reacted with LDL after
      single treatment with trypsin, whereas recognition by the second antibody
      required combined treatment of LDL with trypsin and cholesterol esterase. In
      ELISAs, both antibodies reacted with E-LDL produced in vitro and with lesion
      complement activator derived from human atherosclerotic plaques, but they were
      unreactive with native LDL or ox-LDL. The antibodies stained E-LDL, but not
      native LDL or ox-LDL, that had been artificially injected into arterial vessel
      walls. With the use of these antibodies, we have demonstrated that early human
      atherosclerotic coronary lesions obtained at autopsy as well as lesions examined
      in freshly explanted hearts always contain extensive extracellular deposits of E
      LDL. Terminal complement complexes, detected with a monoclonal antibody specific
      for a C5b-9 neoepitope, colocalized with E-LDL within the intima, which is
      compatible with the proposal that subendothelially deposited LDL is enzymatically
      transformed to a complement activator at the earliest stages in lesion
      development.

PMID- 9514406
TI  - Calcification of human vascular cells in vitro is correlated with high levels of
      matrix Gla protein and low levels of osteopontin expression.
AB  - The cellular and molecular events leading to calcification in atherosclerotic
      lesions are unknown. We and others have shown that bone-associated proteins,
      particularly matrix Gla protein (MGP) and osteopontin (OP), can be detected in
      atherosclerotic lesions, thus suggesting an active calcification process. In the
      present study, we aimed to determine whether human vascular smooth muscle cells
      (VSMCs) could calcify in vitro and to determine whether MGP and OP have a role in
      vascular calcification. We established that human aortic VSMCs and placental
      microvascular pericytes spontaneously form nodules in cell culture and induce
      calcification, as detected by von Kossa's method, Alizarin red S staining, and
      electron microscopy. The cells in calcifying nodules differed from those in
      monolayer cultures by expressing higher levels of the SMC markers alpha-SM actin,
      SM22alpha, and calponin. In addition, Northern blot analysis revealed that in
      human VSMCs, calcification was associated with increased levels of MGP mRNA. In
      contrast, OP mRNA was barely detectable in calcified human VSMCs and pericyte
      nodules, nor was OP protein detected, suggesting that OP was not necessary for
      calcification to occur. These studies reveal that human VSMCs are capable of
      inducing calcification and that MGP may have a role in human vascular
      calcification.

PMID- 9514407
TI  - A novel homozygous missense mutation in the apo A-I gene with apo A-I deficiency.
AB  - We analyzed the genetic defect in a 67-year-old Japanese male patient with
      apolipoprotein (apo) A-I and high density lipoprotein (HDL) deficiencies, corneal
      opacities, and coronary artery disease. The plasma concentrations of apoA-I and
      HDL cholesterol were 2.9 to 7.3 mg/dL and 0.08 to 0.19 mmol/L, respectively. The
      lecithin:cholesterol acyltransferase (LCAT) activity and cholesterol
      esterification rate were <40% of normal control values. LCAT mass was 550% of
      normal control. Sequence analysis of polymerase chain reaction-amplified DNA of
      the proband's apoA-I gene showed a homozygous T-to-A transition resulting in the
      substitution of Val 156 with Glu (apoA-I Oita). Direct sequencing of samples
      obtained from other family members showed that the brother was homozygous,
      whereas the son was a heterozygous carrier of apoA-I Oita. The heterozygote for
      apo A-I Oita showed nearly 60% of normal apoA-I and normal HDL cholesterol
      levels. In vivo turnover studies in rabbits demonstrated that the variant apoA-I
      was rapidly cleared from plasma compared with normal human apoA-I. Our data
      suggest that the Val156Glu substitution is associated with apoA-I and HDL
      deficiency, partial LCAT deficiency, and corneal opacities and that Val156 of
      apoA-I may play an important role in apoA-I function.

PMID- 9514408
TI  - Human vascular smooth muscle cells express receptors for CC chemokines.
AB  - Arteriosclerotic lesions are characterized by the accumulation of T lymphocytes
      and monocytes and the proliferation of intimal smooth muscle cells. Expression of
      the chemokine monocyte chemoattractant protein-1 (MCP- 1) has been observed in
      arteriosclerotic plaques and has been proposed to mediate the transendothelial
      migration of mononuclear cells. More recently, MCP-1 has been proposed to affect
      the proliferation and migration of vascular smooth muscle cells (VSMCs). We have
      used reverse transcription-polymerase chain reaction (RT-PCR) to investigate
      chemokine mRNA expression in human arteriosclerotic lesions obtained from
      surgical biopsy of diseased vascular tissue and show, in addition to MCP-1,
      expression of the chemokine macrophage inflammatory protein-1alpha (MIP-1alpha)
      at higher levels than in "normal" aortic tissue. We have also used RT-PCR to
      characterize the expression of known chemokine receptors by primary human VSMCs.
      Messenger RNA for the MIP-1alpha/RANTES receptor, CCR-1, and the MCP-1/MCP-3
      receptor, CCR-2, was expressed by unstimulated VSMCs grown under serum-free
      culture conditions for 24 hours. The receptors CCR-3, CCR-4, CCR-5, CXCR-1, and
      CXCR-2 were not expressed by VSMCs. The presence of functionally coupled
      receptors for MIP-1alpha on VSMCs was demonstrated by specific binding of
      biotinylated MIP-1alpha and increases in intracellular Ca2+ levels after exposure
      to this chemokine. Taken together, these results suggest that chemokines are
      likely to be involved in arteriosclerosis and may play a role in modulating the
      function of VSMCs in vivo.

PMID- 9514409
TI  - Differential involvement of tyrosine and serine/threonine kinases in platelet
      integrin alphaIIbbeta3 exposure.
AB  - The relative contributions of protein tyrosine kinases (PTKs) and protein kinase
      C isoenzymes (PKCs), a family of serine/threonine kinases, in integrin
      alpha(IIb)beta3 (glycoprotein IIb/IIIa) exposure are the subject of much
      controversy. In the present study we measured the effect of the PTK inhibitor
      herbimycin A and the PKC inhibitor bisindolylmaleimide I on 125I-fibrinogen
      binding to alpha(IIb)beta3 and on aggregation/secretion induced by different
      agonists. Dose-response studies showed complete inhibition of alpha(IIb)beta3
      exposure by 30 micromol/L (ADP stimulation) and 35 to 40 micromol/L (alpha
      thrombin stimulation) herbimycin A. In contrast, inhibition of exposure by
      bisindolylmaleimide I varied from none (for ADP and epinephrine), to 30% (for
      platelet-activating factor), and to approximately 80% (for alpha-thrombin).
      Studies with a submaximal dose of herbimycin A (approximately 50% inhibition of
      the ADP-response) and a maximal dose of bisindolylmaleimide I showed that optical
      aggregation had a similar sensitivity to the inhibitors as alpha(IIb)beta3
      exposure with minimal interference by secreted ADP. Thus, the relative
      contributions of tyrosine and serine/threonine kinases in alpha(IIb)beta3
      exposure and aggregation differ among the different agonists, with an exclusive
      role for PTKs in ADP- and epinephrine-induced responses and a role for both PTKs
      and PKCs in responses induced by platelet-activating factor and alpha-thrombin.

PMID- 9514410
TI  - LDL hypercholesterolemia is associated with accumulation of oxidized LDL,
      atherosclerotic plaque growth, and compensatory vessel enlargement in coronary
      arteries of miniature pigs.
AB  - The association between accumulation of oxidized low density lipoprotein (LDL)
      and (1) progression of atherosclerotic plaques and (2) compensatory enlargement
      was assessed in the coronary arteries of LDL-hypercholesterolemic miniature pigs.
      In miniature pigs fed a 4% cholesterol diet, LDL cholesterol levels increased
      from 27+/-3.5 mg/dL (mean+/-SEM, n=36) to 250+/-28 mg/dL (n=10), 260+/-15 mg/dL
      (n=6), and 260+/-17 mg/dL (n=10) at 6, 14, and 24 weeks, respectively. Mean
      intimal areas of lesions in the left anterior descending coronary artery of
      hypercholesterolemic pigs were 0.16+/-0.046 mm2 at 6 weeks (n=10) and increased
      5.4-fold (n=6, P<.05) and 10.6-fold (n=10, P<.001) at 14 and 24 weeks,
      respectively. Plaque growth was associated with an increase in mean internal
      elastic lamina area, from 1.44+/-0.17 to 4.38+/-0.52 mm2 (P=.007) and in mean
      luminal area from 1.42+/-0.15 mm2 in control pigs to 4.38+/-0.52 mm2 in pigs fed
      a cholesterol diet for 24 weeks (P=.007 vs control). Levels of total LDL in the
      intima, measured immunocytochemically, were 0.031+/-0.0098, 0.11+/-0.057 (P< or
      =.05), and 0.43+/-0.082 U (P<.001) at 6, 14, and 24 weeks, respectively.
      Corresponding levels of oxidized LDL were 0.034+/-0.023, 0.11+/-0.050 (P<.05),
      and 0.44+/-0.065 U (P<.001), respectively, suggesting that virtually all LDL in
      the intima is oxidized. Levels of oxidized LDL in the lesions were correlated
      with the intimal areas (r=.85, P<.0001) but were independent of plasma levels of
      LDL cholesterol and of oxidized LDL. Plaque levels of oxidized LDL were also
      correlated with internal elastic lamina areas (r=.72, P<.0001) and with luminal
      areas (r=.50, P=.0098). Plaque growth in the coronary arteries of LDL
      hypercholesterolemic miniature pigs is associated with (1) an increase in plaque
      levels of oxidized LDL at constant plasma levels of LDL cholesterol and of
      oxidized LDL and (2) compensatory vessel enlargement proportional to plaque
      levels of oxidized LDL.

PMID- 9514411
TI  - Effects of intracellular free cholesterol accumulation on macrophage viability: a
      model for foam cell death.
AB  - This study was designed to identify cellular responses associated with free
      cholesterol (FC) accumulation in model macrophage foam cells. Mouse peritoneal
      macrophages (MPMs) or J774 macrophages were loaded with cholesteryl esters using
      acetylated LDL and FC/phospholipid dispersions and were subsequently exposed to
      an acyl coenzyme A:cholesterol acyltransferase (ACAT) inhibitor. This treatment
      produced a rapid accumulation of cellular FC. The FC that accumulated due to ACAT
      inhibition was more readily available for efflux to 2-hydroxypropyl-beta
      cyclodextrin (which removes cholesterol from the plasma membrane) than FC in
      untreated control cells. After a 3-hour exposure to an ACAT inhibitor, a
      significant increase in phospholipid synthesis was seen, followed by the leakage
      of LDH after 12 hours of treatment. We also observed, by electron and
      fluorescence microscopy, morphological indications of both apoptosis and necrosis
      in cells treated with an ACAT inhibitor. In addition, inhibition of ACAT for 48
      hours resulted in the formation of FC crystals in MPMs but not in J774 cells. If
      compound 3beta-[2-(diethylamino)ethoxy]androst-5-en-17-one (U18666A), which
      modulates intracellular trafficking of cholesterol, was added together with the
      ACAT inhibitor, each of the metabolic changes elicited by the accumulation of
      excess FC was either diminished or eliminated. The protective affect of U18666A
      was not due to a decrease in cellular FC concentrations, because cells treated
      with an ACAT inhibitor accumulated similar amounts of FC in the presence or
      absence of U18666A. Thus, treatment with U18666A results in the sequestering of
      FC in a pool that prevents it from causing various responses to FC deposition in
      macrophages. The metabolic changes that were produced when these model foam cells
      were treated with the ACAT inhibitor parallel the pathological events that have
      been shown to occur in the developing atherosclerotic plaque.

PMID- 9514412
TI  - Extracellular matrix modulates macrophage functions characteristic to atheroma:
      collagen type I enhances acquisition of resident macrophage traits by human
      peripheral blood monocytes in vitro.
AB  - Activated resident macrophages sustain atheroma, and a high macrophage content is
      associated with plaque vulnerability. Factors leading to differentiation and
      activation of these blood-derived cells remain largely uncharacterized. We
      investigated the contribution of interaction with collagen type I, the
      predominant component of atherosclerotic matrix, to differentiation and
      modulation of characteristic macrophage functions, including intracellular lipid
      accumulation and production of the typical matrix-degrading enzyme matrix
      metalloproteinase (MMP)-9. When used as an adhesion substrate for human
      peripheral blood monocytes in vitro, collagen type I increased monocyte
      differentiation, assessed by analysis of CD71 expression and cell spreading.
      Culturing on collagen type I doubled the number of differentiated monocytes at 24
      hours (44.9+/-1.4% versus 18.4+/-1.7% on uncoated dishes, P<.001, n=3 independent
      experiments) and was a stronger stimulus for differentiation than phorbol
      myristate acetate, a known inducer of monocyte differentiation. The effect of
      substrate on intracellular accumulation of modified lipoproteins was assessed by
      quantitative confocal microscopy of monocytes incubated with fluorescent
      acetylated LDL. The collagen type I substrate also doubled the number of
      macrophages containing intracellular lipid and significantly increased the
      individual intracellular loading. Monocytes cultured on collagen type I also
      released more MMP-9 than did cells plated directly on plastic. The role of
      monocyte spreading was further assessed by treatment with colchicine, an
      inhibitor of cytoskeletal function, or with genistein, a nonspecific inhibitor of
      tyrosine kinases, shown to participate in cell adhesion. Cell spreading was
      inhibited in 72.3+/-6.7% of colchicine-treated and in 62.4+/-6.4% of genistein
      treated monocytes (n=3, P<.01 in both cases). The same conditions also decreased
      secretion of MMP-9, and genistein reduced the number of acetylated LDL-containing
      cells (from 286+/-7 to 184+/-8 cells/mm2 with genistein, n=3, P<.001). Data
      showed a strong correlation (r>.98) between monocyte spreading on collagen type I
      and intracellular lipid accumulation. Our results indicate that interaction with
      vascular matrix may play an important role in differentiation of peripheral blood
      monocytes into resident lipid-laden macrophages, which act as central stimulators
      throughout the natural history of atheroma.

PMID- 9514413
TI  - Effects of reducing dietary saturated fatty acids on plasma lipids and
      lipoproteins in healthy subjects: the DELTA Study, protocol 1.
AB  - Few well-controlled diet studies have investigated the effects of reducing
      dietary saturated fatty acid (SFA) intake in premenopausal and postmenopausal
      women or in blacks. We conducted a multicenter, randomized, crossover-design
      trial of the effects of reducing dietary SFA on plasma lipids and lipoproteins in
      103 healthy adults 22 to 67 years old. There were 46 men and 57 women, of whom 26
      were black, 18 were postmenopausal women, and 16 were men > or =40 years old. All
      meals and snacks, except Saturday dinner, were prepared and served by the
      research centers. The study was designed to compare three diets: an average
      American diet (AAD), a Step 1 diet, and a low-SFA (Low-Sat) diet. Dietary
      cholesterol was constant. Diet composition was validated and monitored by a
      central laboratory. Each diet was consumed for 8 weeks, and blood samples were
      obtained during weeks 5 through 8. The compositions of the three diets were as
      follows: AAD, 34.3% kcal fat and 15.0% kcal SFA; Step 1, 28.6% kcal fat and 9.0%
      kcal SFA; and Low-Sat, 25.3% kcal fat and 6.1% kcal SFA. Each diet provided
      approximately 275 mg cholesterol/d. Compared with AAD, plasma total cholesterol
      in the whole group fell 5% on Step 1 and 9% on Low-Sat. LDL cholesterol was 7%
      lower on Step 1 and 11% lower on Low-Sat than on the AAD (both P<.01). Similar
      responses were seen in each subgroup. HDL cholesterol fell 7% on Step 1 and 11%
      on Low-Sat (both P<.01). Reductions in HDL cholesterol were seen in all subgroups
      except blacks and older men. Plasma triglyceride levels increased approximately
      9% between AAD and Step 1 but did not increase further from Step 1 to Low-Sat.
      Changes in triglyceride levels were not significant in most subgroups.
      Surprisingly, plasma Lp(a) concentrations increased in a stepwise fashion as SFA
      was reduced. In a well-controlled feeding study, stepwise reductions in SFA
      resulted in parallel reductions in plasma total and LDL cholesterol levels. Diet
      effects were remarkably similar in several subgroups of men and women and in
      blacks. The reductions in total and LDL cholesterol achieved in these different
      subgroups indicate that diet can have a significant impact on risk for
      atherosclerotic cardiovascular disease in the total population.

PMID- 9514414
TI  - Hyperinsulinemia and cardiovascular disease in elderly men: the Honolulu Heart
      Program.
AB  - Hyperinsulinemia has been associated with cardiovascular disease (CVD), but
      whether this relation is independent of other CVD risk factors is uncertain. Most
      studies have focused on coronary heart disease (CHD), but few have included
      peripheral vascular disease (PVD) and stroke. Moreover, evidence in elderly and
      minority populations is limited. Between 1991 and 1993, 3562 elderly (71 to 93
      years) Japanese-American men from the Honolulu Heart Program were examined and
      had fasting insulin levels measured. Hyperinsulinemia, defined as a fasting
      insulin > or =95th percentile among nonobese men with normal glucose tolerance
      and no diabetic history or medication use, was observed in 22% of the population.
      Subjects with hyperinsulinemia had a more adverse CVD risk factor profile and had
      higher age-adjusted prevalences of CHD, angina, PVD, thromboembolic stroke, and
      hemorrhagic stroke compared with those without hyperinsulinemia. Age-adjusted
      fasting insulin levels but not 2-hour levels were also significantly elevated
      (P<.01) in those with prevalent CVD compared with those without. In logistic
      regression analyses, adjustment for multiple CVD risk factors attenuated the
      relations of hyperinsulinemia with CHD, angina, and PVD to nonsignificant levels,
      whereas those involving thromboembolic and hemorrhagic stroke were strengthened
      and remained significant (odds ratios=2.27 and 7.53, 95% confidence
      intervals=1.25 to 4.13 and 1.65 to 34.25, respectively). When multivariate
      analyses were restricted to nondiabetic subjects, associations were slightly
      weaker and in general nonsignificant. Nondiabetic men with thromboembolic stroke
      were twice as likely to have hyperinsulinemia as those who were stroke-free,
      although this association was of borderline significance (odds ratio= 1.99, 95%
      confidence interval=0.95 to 4.17, P=.069). In subjects with elevated total
      cholesterol levels, somewhat stronger associations were observed for PVD and
      stroke but not for CHD. Although further prospective studies are indicated,
      particularly for PVD and stroke, these cross-sectional results are consistent
      with an indirect role for insulin in CVD, wherein hyperinsulinemia or an
      underlying insulin-resistant state may adversely affect other CVD risk factors or
      serve as a marker for an atherogenic or thrombogenic state.

PMID- 9514416
TI  - Influence of apoE content on receptor binding of large, bouyant LDL in subjects
      with different LDL subclass phenotypes.
AB  - We investigated the influence of apolipoprotein (apo) E-containing particles on
      LDL receptor binding of large, buoyant LDL subfractions (LDL I) from subjects
      with predominantly large (phenotype A) and small (phenotype B) LDL particles.
      Direct binding by human fibroblast LDL receptors was tested at 4 degrees C before
      and after removal of apoE-containing particles by immunoaffinity chromatography.
      The binding affinity of total LDL I in phenotype B was greater than that in
      phenotype A (Kd of 1.83+/-0.3 and 3.43+/-0.9 nmol/L, respectively, P<.05). LDL I
      from phenotype B subjects had a higher apoE to apoB molar ratio than did that
      from phenotype A (0.16+/-0.04 versus 0.06+/-0.02, P<.05). Nondenaturing gradient
      gel electrophoresis of apoE-containing LDL I isolated by immunoaffinity
      chromatography revealed a substantially larger peak particle diameter than in
      apoE-free LDL I, and comparison of LDL I composition before and after
      immunoaffinity chromatography suggested an increase in triglyceride content of
      apoE-containing particles. After removal of these particles, there was a greater
      than twofold reduction in LDL receptor affinity of phenotype B LDL (Kd of 1.83+/
      0.3 to 3.76+/-0.6, P<.01), whereas in phenotype A no change was observed (Kd of
      3.43+/-0.9 to 3.57+/-0.4, respectively). The receptor affinity of apoE-free LDL I
      from phenotype A and B subjects did not differ. These findings confirm that
      large, buoyant LDL particles from phenotype B subjects have a higher LDL receptor
      affinity than does LDL I from phenotype A subjects and suggest that this
      difference is due to an increased content of large, triglyceride-enriched, apoE
      containing lipoproteins. It is possible that the accumulation of these particles
      reflects abnormalities in the metabolism of remnant lipoproteins that contribute
      to atherosclerosis risk in phenotype B subjects.

PMID- 9514417
TI  - LDL induces transcription factor activator protein-1 in human endothelial cells.
AB  - Low density lipoprotein (LDL) has been shown to perturb endothelial cells, with
      manifestations ranging from alterations in free radicals and arachidonate
      metabolism to stress fiber formation and monocyte recruitment. Some of these
      changes are regulated by LDL at the transcriptional level. Using mobility shift
      assays with consensus sequences for various transcription factors, we have
      detected an increase in activator protein 1 (AP-1), but not nuclear factor-kappaB
      (NF-kappaB), binding in human umbilical vein endothelial cells exposed to LDL.
      Following transfection, AP-1-driven chloramphenicol acetyltransferase and AP-1
      driven-luciferase are upregulated by LDL. In contrast, there is no effect on NF
      kappaB-driven chloramphenicol acetyltransferase. AP-1 increases in a biphasic
      fashion, with the first peak occurring 6 hours after and the second 48 hours
      after exposure to LDL. This AP-1 binding increase involves c-Jun, but not c-Fos,
      as shown by gel supershift, Northern hybridization, and Western blotting
      analyses. c-Jun mRNA levels are elevated by 9 hours after and remain so until at
      least 24 hours after exposure to LDL. c-Jun protein levels increase at 12 hours
      and continue to rise for 24 hours after exposure to LDL. Moreover, this LDL
      increased AP-1 binding is suppressed by several protein kinase (PK) inhibitors:
      the PKC inhibitor calphostin C, the cAMP-dependent PK inhibitor H89, and the
      tyrosine PK inhibitors genistein and lavendustin A. This study demonstrates that
      (1) LDL is an endothelial agonist distinct from other cell stimulators, such as
      cytokines, endotoxin, and phorbol 12-myristate 13-acetate, because LDL appears to
      activate human umbilical vein endothelial cells predominantly through the
      transcription factor AP-1 and not NF-kappaB; and (2) LDL increases AP-1 via
      mechanisms involving multiple kinase activities and c-Jun transcription.

PMID- 9514415
TI  - Plasma lipoproteins support prothrombinase and other procoagulant enzymatic
      complexes.
AB  - The prothrombinase complex (factor [F]Xa, FVa, calcium ions, and lipid membrane)
      converts prothrombin to thrombin (FIIa). To determine whether plasma lipoproteins
      could provide a physiologically relevant surface, we determined the rates of FIIa
      production by using purified human coagulation factors, and isolated fasting
      plasma lipoproteins from healthy donors. In the presence of 5 nmol/L FVa, 5
      nmol/L FXa, and 1.4 micromol/L prothrombin, physiological levels of very low
      density lipoprotein (VLDL) (0.45 to 0.9 mmol/L triglyceride, or 100 to 200
      micromol/L phospholipid) yielded rates of 2 to 8 nmol Flla x L(-1) x s(-1) in a
      donor-dependent manner. Low density lipoprotein (LDL) and high density
      lipoprotein (HDL) also supported prothrombinase but at much lower rates (< or
      =1.0 nmol FIIa x L(-1) x s[-1]). For comparison, VLDL at 2 mmol/L triglyceride
      yielded approximately 50% the activity of 2X10(8) thrombin-activated platelets
      per milliliter. Although the FIIa production rate was slower on VLDL than on
      synthetic phosphatidylcholine/phosphatidylsenne vesicles (approximately 50 nmol
      FIIa x L(-1) x s[-1]), the prothrombin Km values were similar, 0.8 and 0.5
      micromol/L, respectively. Extracted VLDL lipids supported rates approaching those
      of phosphatidylcholine/phosphatidylserine vesicles, indicating the importance of
      the intact VLDL conformation. However, the presence of VLDL-associated, factor
      specific inhibitors was ruled out by titration experiments, suggesting a key role
      for lipid organization. VLDL also supported FIIa generation in an assay system
      comprising 0.1 nmol/L FVIIa; 0.55 nmol/L tissue factor; physiological levels of
      FV, FVIII, FIX, and FX; and prothrombin (3 nmol/L FIIa x L(-1) x s[-1]). These
      results indicate that isolated human VLDL can support all the components of the
      extrinsic coagulation pathway, yielding physiologically relevant rates of
      thrombin generation in a donor-dependent manner. This support is dependent on the
      intact lipoprotein structure and does not appear to be regulated by specific VLDL
      associated inhibitors. Further studies are needed to determine the extent of this
      activity in vivo.

PMID- 9514418
TI  - Increase of vitamin E content in LDL and reduction of atherosclerosis in
      cholesterol-fed rabbits by a water-soluble antioxidant-rich fraction of Salvia
      miltiorrhiza.
AB  - Antioxidants that prevent LDL from oxidation may reduce atherosclerosis. Salvia
      miltiorrhiza Bunge is a Chinese herb widely used for the treatment of
      atherosclerosis-related disorders. Salvianolic acid B (Sal B), a water-soluble
      polyphenolic antioxidant isolated from the roots of this plant, was found to
      scavenge 1,1-diphenyl-2-picrylhydrazyl radicals and inhibit LDL oxidation more
      effectively than probucol. In order to evaluate the antiatherogenic potential,
      New Zealand White rabbits were fed for 12 weeks a normal diet, a high cholesterol
      diet, a high cholesterol diet containing 1% probucol, or a high cholesterol diet
      containing a 5% water-soluble extract of S miltiorrhiza (SM). Both SM and
      probucol feeding reduced plasma cholesterol. LDLs from the SM-treated group were
      more resistant to Cu2+-induced oxidation and contained more vitamin E (21.7+/-2.1
      mmol/micromol LDL cholesterol) than did LDLs from the high cholesterol diet group
      (9.6+/-1.8 nmnol/micromol LDL cholesterol) (P<.005). Endothelial damage,
      determined at week 6, was reduced by 53% in the SM group (P<.01). SM treatment
      reduced the atherosclerotic area in the abdominal aorta by 56% (P<.005) and
      cholesterol deposition in the thoracic aorta by 50% (P<.005). The severity of
      atherosclerosis in the SM group was significantly reduced after adjustment by
      using cholesterol exposure as an index of the cholesterol-lowering effect. This
      study concludes that the reduction of atherosclerosis by SM relies not only on
      its cholesterol-lowering effect but more heavily on its antioxidant potential to
      prevent endothelial damage and inhibit LDL oxidative modification in
      hypercholesterolemic animals.

PMID- 9514420
TI  - Possible involvement of m-calpain in vascular smooth muscle cell proliferation.
AB  - Vascular smooth muscle cell (VSMC) proliferation still remains a poorly
      understood process, although it is believed to play a critical role in
      pathological states, including atherosclerosis and hypertension. Several reports
      have suggested that proteases may be directly involved in this process; however,
      it was still unclear which protease is responsible for VSMC proliferation. In
      this study, by use of a cell-permeable calpain inhibitor (calpeptin;
      benzyloxycarbonyl-Leu-nLeu-H), its analogue (benzyloxycarbonyl-Leu-Met-H), the
      cell-impermeable serine protease inhibitor leupeptin, and antisense
      oligonucleotide against m-calpain to inhibit proliferation of primarily cultured
      human VSMCs, we investigated whether calcium-activated neutral protease (calpain)
      is involved in VSMC proliferation. Calpeptin and its analogue, more specific for
      m-calpain, equally inhibited the proliferation of VSMCs in a dose-related manner,
      whereas a more limited antiproliferative effect was observed in leupeptin-treated
      VSMCs. Antisense oligonucleotide against m-calpain, but not scrambled antisense,
      dose-dependently inhibited m-calpain expression and proliferation of VSMCs.
      Maximal inhibition was an approximately 50% reduction of cell number and m
      calpain antigen observed at 50 micromol/L of antisense oligonucleotide. Calpeptin
      or antisense oligonucleotide against m-calpain increased the expression of the
      endogenous calpain substrate pp125FAK (focal adhesion kinase), whereas the
      expression of the endogenous calpain inhibitor calpastatin was not affected.
      These results suggest that the proliferation of VSMCs requires protease activity,
      some of which is due to m-calpain.

PMID- 9514419
TI  - Beta-fibrinogen gene polymorphism (C148-->T) is associated with carotid
      atherosclerosis: results of the Austrian Stroke Prevention Study.
AB  - Polymorphisms at the beta-fibrinogen locus have been shown to be associated with
      plasma concentration of fibrinogen and coronary heart disease. The effect of the
      genetic heterogeneity of fibrinogen on carotid atherosclerosis has not been
      determined so far. We examined the influence of the C148 --> T polymorphism on
      carotid disease in a large cohort of middle-aged to elderly subjects without
      evidence of neuropsychiatric disease. This polymorphism is located close to the
      consensus sequence of the interleukin-6 element and may represent a functional
      sequence variant. The genotype of 399 randomly selected, neurologically
      asymptomatic individuals, aged 45 to 75 years, was determined by denaturing
      gradient gel electrophoresis. Carotid atherosclerosis was assessed by color-coded
      duplex scanning and was graded on a five-point scale ranging from 0 (=normal) to
      5 (=complete luminal obstruction). The C/C, C/T, and T/T genotypes were noted in
      226 (56.6%), 148 (37.1 %), and 25 (6.3%) individuals, respectively. The T/T
      genotype group demonstrated higher grades of carotid atherosclerosis than did the
      C/C and C/T genotypes (P=.003). Logistic regression analysis created a model of
      independent predictors of carotid atherosclerosis that included apolipoprotein B
      (odds ratio [OR], 1.17/10 mg/dL), age (OR, 2.46/10 years), lifetime tobacco
      consumption (OR, 1.03/1000 g), presence of the beta-fibrinogen promoter T/T
      genotype (OR, 6.17), plasma fibrinogen concentration (OR, 1.05/10 mg/dL), and
      cardiac disease (OR, 1.80). These data suggest that the beta-fibrinogen promoter
      T/T148 genotype represents a genetic risk factor for carotid atherosclerosis in
      the middle-aged to elderly.

PMID- 9514421
TI  - Prophylactic oophorectomy in colorectal carcinoma: preliminary results of a
      randomized, prospective trial.
AB  - Controversy exists regarding the role of prophylactic oophorectomy during
      resection for primary colorectal cancer. PURPOSE: A prospective, randomized trial
      was initiated to evaluate the influence of oophorectomy on recurrence and
      survival in patients with Dukes Stages B and C colorectal cancer. METHOD: Between
      November 1986 and March 1997, 155 patients were randomized to oophorectomy or no
      oophorectomy at laparotomy for resection of colorectal cancer. RESULTS: No
      incidence of gross or microscopic metastatic disease to the ovary was found among
      77 patients randomized to oophorectomy, in contrast to previous reports.
      Preliminary crude survival curves suggested a survival benefit for oophorectomy
      between two and three years from surgery, but Kaplan-Meier survival analysis
      indicated that this was not statistically significant and the benefit does not
      appear to persist at five years. Kaplan-Meier curves of recurrence-free survival,
      however, suggest a more substantial separation of the curves, with 80 percent vs.
      65 percent five-year disease-free survival for oophorectomy vs. nonoophorectomy,
      but further patient accrual is necessary to provide sufficient statistical power.
      CONCLUSIONS: Occult colorectal carcinoma metastatic to the ovaries has not been
      documented in this series of putative Dukes Stages B and C tumors. The
      possibility of a recurrence-free survival advantage emphasizes the need to
      continue this preliminary work.

PMID- 9514422
TI  - DNA index as a significant predictor of recurrence in colorectal cancer.
AB  - PURPOSE: To clarify the prognostic significance of the DNA content in cases of
      colorectal cancer, we investigated the relationship between the DNA content, as
      determined by the DNA ploidy or DNA index, and disease-free survival. RESULTS:
      This study included 201 cases that were treated by curative surgery between 1989
      and 1995 at our hospital. 68 were diploid and 133 were aneuploid. The mean DNA
      index of these tumors was 1.42. Recurrence occurred in 30 cases (14.9 percent).
      Tumor site, venous invasion, Dukes stage, DNA ploidy (diploid or aneuploid), and
      a DNA index (less than or greater than 1.4) correlated well with disease-free
      survival. A multivariable analysis suggested the DNA index to be a stronger
      predictor than DNA ploidy. Patients with aneuploid tumors had shorter disease
      free survival than those with diploid tumors (P = 0.011), especially in Dukes
      Stage C cases (P = 0.0209). Patients with a DNA index greater than 1.4 also had a
      shorter disease-free survival than those with a DNA index less than 1.4 (P <
      0.001), especially in Dukes Stage C cases (P = 0.0033). CONCLUSIONS: The DNA
      index value (less than or greater than 1.4) seems to be a stronger predictor than
      DNA ploidy (diploid or aneuploid), and the combination of Dukes stage, tumor
      site, and a DNA index is, therefore, considered to be clinically valuable in
      predicting recurrence in cases of colorectal cancer.

PMID- 9514423
TI  - Curative surgery for colorectal cancer: long-term results and life expectancy in
      the elderly.
AB  - PURPOSE: The long-term prognosis after curative surgery for colorectal cancer was
      evaluated in relation to age and life expectancy as a possible basis for
      assessing the risk to benefit ratios in the elderly. METHODS: Data relating to
      1,256 patients operated on from 1976 to 1994 were stored in a computer database
      prospectively from 1987. Patients were subdivided into four age groups (A = <60
      years; B = 60-69; C = 70-79; D = > or =80). Distribution of general
      contraindications to curative surgery was examined. In the 869 patients who
      underwent curative treatment (A = 206; B = 256; C = 289; D = 118), distribution
      of tumor stage and elective/emergency surgery and the operative mortality rate
      were evaluated. Crude and age-corrected survival curves were calculated in 794
      patients. The median crude survival of each group was related by gender and tumor
      stage to demographic life expectancy, assuming as "relative median survival
      index" the ratio between the two values. RESULTS: General contraindications to
      curative surgery increased significantly with age. The operative mortality rate
      was higher in Group D than in Groups A, B, plus C over the total series (P <
      0.001) and in both elective (P < 0.001) and emergency surgery (P < 0.05).
      Intergroup analysis of long-term survival rates showed significant differences
      between "crude" (P = 0.0057) but not age-corrected (P = 0.66) curves. The
      relative median survival index increased with age, up to approximately 1 in the
      local stages of Groups C and D. CONCLUSIONS: To evaluate long-term results,
      elderly patients should be compared with unaffected, same-age subjects. Because
      the risks may be very high, the surgical policy in the elderly should be
      carefully weighed and related to life expectancy and actual results.

PMID- 9514424
TI  - Monoclonal antibody to lymphocyte function associated antigen-1 improves graft
      versus-host disease.
AB  - We previously showed that intestinal tissue expression of lymphocyte function
      associated antigen-1 is increased in animals with graft-versus-host disease after
      small-bowel transplantation. HYPOTHESIS: Treatment of rats with monoclonal
      antibody to lymphocyte function associated antigen-1 after small-bowel
      transplantation will lessen the severity of graft-versus-host disease. METHODS:
      Graft-versus-host disease was created in Lewis X Brown-Norway F1 rats by
      heterotopic vascularized small-bowel transplantation from Lewis donors.
      Transplanted rats were treated with either saline or various regimens of
      monoclonal antibody to lymphocyte function associated antigen-1. Clinical
      characteristics, weight loss, spleen index, white blood cell counts, native
      intestinal histology, bowel permeability, and survival were then compared between
      groups and appropriate sham-operated and lymphocyte function associated antigen-1
      treated controls. RESULTS: Lymphocyte function associated antigen-1-treated rats
      lost less weight, had larger spleen indexes, more normal white blood cell counts,
      more normal native intestinal histology, less alteration in bowel permeability,
      and longer survival than untreated small-bowel transplantation rats. CONCLUSIONS:
      In this model of graft-versus-host disease after small-bowel transplantation,
      monoclonal antibody to lymphocyte function associated antigen-1 treatment
      decreased the severity of graft-versus-host disease and prolonged rat survival.

PMID- 9514425
TI  - Use of guanylyl cyclase C for detecting micrometastases in lymph nodes of
      patients with colon cancer.
AB  - INTRODUCTION: Guanylyl cyclase C appears to be expressed only in colorectal
      cancer cells in extraintestinal tissues. Thus, guanylyl cyclase C may be useful
      as a marker to detect colorectal cancer micrometastases not detectable by
      histopathology in lymph nodes of patients. METHODS: Twelve patients with colon
      adenocarcinoma, Dukes Stages A through C2, and one patient with a tubulovillous
      adenoma were included in this study. Forty-two lymph nodes were collected from
      fresh surgical specimens, and each was examined by histopathology and reverse
      transcription followed by polymerase chain reaction using guanylyl cyclase C
      specific primers. Histopathology identified colon cancer cells in 6 of 16 lymph
      nodes from five Dukes Stage C patients but not in lymph nodes from the patient
      with a tubulovillous adenoma, the Dukes Stage A patient, or six Dukes Stage B
      patients. Reverse transcription followed by polymerase chain reaction using
      guanylyl cyclase C-specific primers was performed on all 42 lymph nodes. RESULTS:
      Guanylyl cyclase C messenger RNA was not detected by reverse transcription
      followed by polymerase chain reaction in lymph nodes from the patient with the
      tubulovillous adenoma or the patient with Dukes Stage A colon carcinoma. Seven
      lymph nodes from Dukes Stage C patients revealed guanylyl cyclase C messenger RNA
      including six lymph nodes containing histopathologically confirmed metastases. Of
      significance, guanylyl cyclase C messenger RNA was detected in 6 of 21 lymph
      nodes from Dukes Stage B patients. Indeed, clinical staging of two patients could
      be upgraded from B to C using reverse transcription followed by polymerase chain
      reaction and guanylyl cyclase C-specific primers. CONCLUSION: Reverse
      transcription followed by polymerase chain reaction using guanylyl cyclase C
      specific primers might be useful to more accurately assess micrometastases in
      lymph nodes of colorectal cancer patients undergoing disease staging.

PMID- 9514426
TI  - Fecal calprotectin concentration in patients with colorectal carcinoma.
AB  - PURPOSE: The study contained herein was undertaken to investigate fecal
      calprotectin excretion in a series of patients with colorectal carcinoma and to
      determine whether the excretion was influenced by localization or stage of the
      tumor. Furthermore, the effect of surgical treatment on the concentrations was
      studied. Fecal calprotectin was also compared with plasma concentrations of
      calprotectin, carcinoembryonic antigen, and C-reactive protein. METHODS: Fecal
      calprotectin was measured in 119 consecutive patients admitted for treatment of
      colorectal carcinoma. In 116 (97.5 percent) patients, resectional surgery was
      performed. Plasma calprotectin was measured in 90 (76 percent) patients,
      carcinoembryonic antigen in 88 (74 percent) patients, and C-reactive protein in
      82 (69 percent) patients. RESULTS: Median fecal calprotectin concentration in the
      119 patients was 50 (range, 2-950) mg/l, which was significantly (P < 0.0001)
      higher than in 125 control patients (median, 5.2 mg/l). In 23 patients studied
      also after resection, the excretion fell greatly. There were no significant
      differences in fecal calprotectin concentration among patients with different
      tumor stages. Elevated plasma calprotectin concentrations were found in 67 of 90
      (73.3 percent) patients with colorectal carcinoma, compared with elevated fecal
      calprotectin in 111 of 119 (93.3 percent) patients, and there was no significant
      correlation between plasma and fecal calprotectin concentrations. Plasma
      calprotectin concentrations were significantly lower in patients with T1 or T2
      tumors than in those with more advanced stages (P = 0.0025). CONCLUSION:
      Measurement of fecal calprotectin may become a diagnostic tool in detecting
      colorectal carcinoma. The specificity in relation to colorectal carcinoma has
      not, however, been completely investigated. Both neoplastic and inflammatory
      conditions may be associated with elevated values; therefore, it is unlikely that
      calprotectin can predict specific colonic disorders.

PMID- 9514427
TI  - Differential diagnosis of dysplasia-associated lesion or mass and coincidental
      adenoma in ulcerative colitis.
AB  - PURPOSE: This study was undertaken to investigate factors that influenced
      differential diagnosis of dysplasia-associated lesion or mass and coincidental
      adenoma in patients with ulcerative colitis. METHODS: Among 346 patients with
      ulcerative colitis who underwent colonoscopy between 1979 and 1995, 27 patients
      had macroscopic neoplastic lesions and were divided into two groups: those with
      dysplasia-associated lesion or mass (16 patients) and those with adenoma (11
      patients), each being categorized by the presence and absence of dysplasia in the
      flat mucosa adjacent to the elevated lesions, respectively. RESULTS: Thirteen of
      27 patients had dysplasia-associated lesion or mass detected by colonoscopic
      biopsy; 10 of these patients underwent colectomy, and all had dysplasia
      associated lesion or mass in the colectomy specimens. Two patients whose biopsy
      findings were adenoma had an unsuspected dysplasia-associated lesion or mass in
      the operative specimens. In the remaining 12 patients, the macroscopic lesions
      were excised during colonoscopy because of clinical and colonoscopic evidence of
      adenoma. One of them was proved to have dysplasia-associated lesion or mass, and
      the other 11 were confirmed as having adenoma in the polypectomy specimens.
      Patients with dysplasia-associated lesion or mass were significantly younger (P <
      0.05), had longer duration of ulcerative colitis (P < 0.01), and had more
      extensive disease (P < 0.005) than those with adenoma. The colonoscopic
      appearance was plaque-like in 13, sessile in 13, and pedunculated in 2 of the 28
      lesions with dysplasia-associated lesion or mass, whereas it was plaque-like in
      only 1 and sessile or pedunculated in 15 of the 16 lesions with adenoma (P <
      0.001). The mean size of the lesions that were considered to be dysplasia
      associated lesions or mass and adenoma was 1.8 and 0.5 cm, respectively (P <
      0.0001). CONCLUSIONS: Colonoscopic biopsy for detection of dysplasia in the flat
      mucosa adjacent to macroscopic neoplastic lesions is an appropriate preoperative
      approach to distinguish dysplasia-associated lesions or mass from adenomas in
      patients with ulcerative colitis. The statistically significant variables that
      influenced the differential diagnosis were age, duration of disease, extent,
      tumor size, and tumor colonoscopic appearance.

PMID- 9514428
TI  - Blood selenium and glutathione peroxidase status in patients with colorectal
      cancer.
AB  - PURPOSE: It is still controversial whether a low selenium level and a reduced
      activity of the selenium-dependent enzyme, glutathione peroxidase, in blood are
      associated with an increased risk and poor prognosis of cancer in humans. This
      study evaluates whether colorectal cancer patients have lower serum selenium and
      glutathione peroxidase levels than a gender-matched and age-matched control group
      and whether there is a correlation to clinical data and prognosis. METHODS: In a
      retrospective study, serum selenium and glutathione peroxidase activity of 106
      patients with colorectal cancer were determined. Clinical data were provided by
      our long-term follow-up program for colorectal cancer patients. RESULTS: Patients
      with a selenium level <70 microg/l had a significantly lower mean survival time
      and a lower cumulative cancer-related survival rate than patients with a selenium
      level >70 microg/l (P = 0.0009). When considering the different tumor stages, a
      decline of the mean selenium level in the T4 carcinoma group was found in the
      analysis of variance (P < 0.05). The lowest selenium level was found for patients
      with advanced tumor disease and in a preoperative situation, ie., high tumor
      burden. In comparison with the control group, the cancer group showed a
      significant reduction of serum glutathione peroxidase activity (P < 0.01) but no
      significant difference in selenium level. CONCLUSIONS: These results support the
      hypothesis of an association between low selenium level and advanced tumor
      disease. From our data, it cannot be decided whether this phenomenon is more
      likely to be a consequence or a causative factor for development and course of
      the disease.

PMID- 9514429
TI  - Fatigue rate index as a new measurement of external sphincter function.
AB  - PURPOSE: Assessment of sustained voluntary contraction of the external sphincter
      is helpful in evaluating the patient who has a defecation disorder on
      presentation. A new index of external sphincter function is described. METHOD: A
      prospective registry of patients referred for computerized anal manometry using
      standard protocols was reviewed. Patients were grouped by primary symptoms; those
      with overlapping complaints were excluded. The rate of fatigue, defined as the
      change in stationary squeeze over a 40-second period of voluntary contraction,
      was calculated by linear regression analysis. Fatigue rate index, a calculated
      measure of time necessary for the external sphincter to become completely
      fatigued, was determined to permit comparison of external sphincter fatigue in
      patients with different complaints. RESULTS: Twenty-six healthy volunteers (15
      women; mean age, 45 years), 33 patients with a primary complaint of anal seepage
      (13 women; mean age, 53 years), 75 patients with gross incontinence (61 women;
      mean age, 53 years), and 49 patients with severe constipation (41 women; mean
      age, 45 years) were evaluated. Mean resting and squeeze pressures were 55 mmHg
      and 107 mmHg for volunteers, 37 mmHg and 97 mmHg for patients with seepage, 30
      mmHg and 49 mmHg for incontinent patients, and 56 mmHg and 93 mmHg for
      constipated patients. Pudendal neuropathy, as evidenced by a prolonged pudendal
      nerve terminal motor latency (> 2.4 ms), was identified in 13 percent of
      volunteers, 32 percent of patients with seepage, 54 percent of incontinent
      patients, and 38 percent of constipated patients. Mean fatigue rate index was 3.3
      minutes for volunteers, 2.3 minutes for seepage patients, 1.5 minutes for
      incontinent patients, and 2.8 minutes for constipated patients. Compared with
      volunteers and patients with seepage, the incontinent patients had a
      significantly shorter fatigue rate index (P < 0.05; Student's t-test), which was
      independent of the variations in resting pressure (P < 0.05; two-way analysis of
      variance). CONCLUSION: The external anal sphincter is normally subject to
      fatigue. Patients with worsening degrees of incontinence have a predictably lower
      fatigue rate index. Fatigue rate index is a simple measure of external sphincter
      integrity, which may be used in assessment of sphincter function and future
      treatment protocols.

PMID- 9514430
TI  - Successful overlapping anal sphincter repair: relationship to patient age,
      neuropathy, and colostomy formation.
AB  - BACKGROUND: Fecal incontinence from single anal sphincter defects are surgically
      remedial and commonly the result of obstetric injuries. Overlapping anal
      sphincter repair has previously been associated in small series with good results
      in 69 to 97 percent of patients. OBJECTIVES: The aims of this study were to
      assess the results of overlapping anal sphincter repair in one institution and to
      assess the effects of age, presence of a neuropathy, and addition of a temporary
      colostomy on the success of surgery. METHODS: A study of 57 overlapping anal
      sphincter repairs in 56 (54 females) patients at the Royal Prince Alfred Hospital
      during a six-year period was performed. All patients were investigated
      preoperatively with endoanal ultrasound and concentric needle electromyography.
      Patients have been assessed prospectively since 1994 with a questionnaire,
      including a four-point Likert scale of continence level, the St. Mark's
      incontinence scoring system (range, 0-13), the Pescatori incontinence scoring
      system (range, 0-6), and patient assessment of success or failure of the
      overlapping anal sphincter repair. A colostomy was selectively formed in
      conjunction with an overlapping anal sphincter repair in 21 patients (8
      preoperatively, 13 simultaneously), and 18 patients had a concomitant neuropathy
      (3 unilateral, 15 bilateral). RESULTS: After a median follow-up of 18 months,
      median continence scores overall had improved from St. Mark's incontinence
      scoring 13 to 3 (P < 0.0001) and Pescatori incontinence scoring 6 to 2 (P <
      0.0001). Forty-nine of 57 (86 percent) repairs have been successful, and 8 are
      considered to be failures. Twenty-one of 27 (78 percent) repairs in patients
      younger than 40 years of age were successful, as were 28 of 30 (93 percent)
      repairs in patients older than 40 years of age (P = 0.10). Four of 18 (22
      percent) repairs associated with a neuropathy failed compared with 4 of 39 (10
      percent) without a neuropathy (P = 0.21). Improved or normal continence was
      achieved in 17 of 21 (81 percent) patients with a stoma and overlapping anal
      sphincter repair and in 32 of 36 (89 percent) patients with an overlapping anal
      sphincter repair alone (P = 0.32). The presence of a stoma did not improve the
      rate of wound healing by primary intention (62 percent for stoma vs. 64 percent
      for overlapping anal sphincter repair alone; P = 0.55). CONCLUSIONS: Single anal
      sphincter defects can be successfully treated with an overlapping anal sphincter
      repair. There is no improvement in primary healing with selective stoma
      formation. Age of the patient and presence of a neuropathy should not detract
      from proceeding with overlapping anal sphincter repair when singular anal
      sphincter defects are detected on endoanal ultrasound in muscle that is still
      active.

PMID- 9514431
TI  - No correlation between perineal position and pudendal nerve terminal motor
      latency in healthy perimenopausal women.
AB  - BACKGROUND: Significant associations between perineal descent and pudendal nerve
      latency have previously been described in fecally incontinent patients. This has
      led to the hypothesis that pelvic floor muscle and nerve injury initiated by
      childbirth might progress and cause fecal incontinence. PURPOSE: The study
      contained herein was undertaken to test whether changes in perineal position and
      pudendal nerve latency were associated in a population of healthy middle-aged
      women. METHODS: A cross-sectional study of 144 women were selected randomly from
      the Danish National Register; they had a mean age of 50 (range, 45-57) years and
      a mean parity of 2 (range, 0-6). Perineal position at rest and during simulated
      defecation and pudendal nerve terminal motor latency were measured. All
      examinations were performed by one of the authors (AMR) and without the knowledge
      of parity. RESULTS: The perineal position both at rest and during straining was
      significantly lowered, and the pudendal nerve terminal motor latency was
      significantly prolonged with increasing numbers of vaginal deliveries (data not
      shown). There was, however, no association between pudendal nerve terminal motor
      latency and perineal position at rest (correlation coefficient, r = -0.15, P =
      0.1) or during simulated defecation (r = -0.08, P = 0.4). CONCLUSION: Small but
      significant effects of vaginal deliveries were detected in a random population of
      healthy perimenopausal women. However, because perineal descent and pudendal
      nerve latency were not associated, our findings do not support the hypothesis
      that damage induced by vaginal delivery to the pudendal nerves and pelvic floor
      will progress.

PMID- 9514432
TI  - Transanal approach to rectocele repair may compromise anal sphincter pressures.
AB  - PURPOSE: This study prospectively assessed the functional results, particularly
      anal sphincter impairment, following transanal repair of rectocele for chronic
      intractable constipation. METHOD: Twenty-one consecutive women (mean age, 47.7
      (standard error of the mean, 2.7) years) had the diagnosis of rectocele
      obstructing defecation made on synchronized anal manometry, electromyography, and
      cinedefecography. All underwent a standardized transanal repair with controlled
      anal stretching (maximum of 4 cm) from self-retaining anal retractors. The
      clinical function and anorectal manometry were assessed before surgery and were
      repeated six months later. RESULTS: All 21 patients were subjectively satisfied
      with the relief from constipation after surgery. There were significant
      improvements in the straining at defecation (before, n = 19; after, n = 3; P =
      0.001), need to digitate per vagina (before, n = 16; after, n = 0; P = 0.001),
      stool frequency (before, 3.8 (0.7) times weekly; after, 8.6 (1.2); P = 0.004),
      and laxative requirements (before, n = 7; after, n = 0; P = 0.03). Although none
      were clinically incontinent, there was a mean 28 mmHg impairment in resting (P <
      0.05) and 42.6 mmHg impairment in maximum squeeze anal pressures (P < 0.05) after
      operations. There was no other morbidity. CONCLUSION: Transanal rectocele repair
      effectively improves constipation problems, at the risk of impaired anal
      sphincter function. Although clinical incontinence was minimum, an alternative
      approach to rectocele repair should be considered when anal sphincters are lax.

PMID- 9514433
TI  - Biofeedback training in patients with fecal incontinence.
AB  - PURPOSE: This study was undertaken to assess the functional results of
      biofeedback training in patients with fecal incontinence in relation to clinical
      presentation and anorectal manometry results. METHODS: Twenty-six consecutive
      patients with fecal incontinence were treated with biofeedback training using
      anorectal manometry pressure for visual feedback. Ten patients had passive
      incontinence only, six patients had urge incontinence, and ten patients had
      combined passive and urge incontinence. RESULTS: Patients with urge incontinence
      had a lower maximum voluntary contraction pressure (92+/-12 mmHg) and a lower
      maximum tolerable volume (78+/-13 ml) than patients with passive incontinence
      (140+/-43 mmHg and 166+/-73 ml). Twenty-two patients completed the treatment,
      five patients (23 percent) showed excellent improvement, nine patients (41
      percent) had good results, and eight (36 percent) patients showed no improvement.
      At follow-up on average of 21 months after therapy, 41 percent of our patients
      reported continued improvement. The maximum tolerable volume was higher in those
      with excellent (140.4+/-6.8 ml) or good (156.3+/-6.64 ml) results of therapy than
      it was in those with poor results (88.5+/-2.5 ml). Greater asymmetry of the anal
      sphincter also correlated to poor results. CONCLUSION: Biofeedback therapy
      improved continence immediately after training and at follow-up after 21 months,
      but the initial results were better. The urge fecal incontinence seems to be
      related to function of the external anal sphincter and to the maximum tolerable
      volume. Low maximum tolerable volume and anal sphincter asymmetry were associated
      with a poor outcome of therapy.

PMID- 9514434
TI  - Pelvic floor procedures produce no consistent changes in anatomy or physiology.
AB  - PURPOSE: Postanal repair was designed to restore both anatomy and function of the
      anal canal in neurogenic fecal incontinence. In most series, the degree of
      continence is improved in fewer than 50 percent of patients. Adding anterior
      levatorplasty and sphincter plication (total pelvic floor repair) is claimed to
      improve functional results. We performed a randomized trial comparing postanal
      and total pelvic floor repair for neurogenic incontinence. METHOD: Twenty female
      patients were studied. All had Type D incontinence (Parks and Browning). Anal
      manometry, defecography, and grading of the degree of continence were repeated 12
      weeks after surgery to assess changes in clinical, manometric, and radiologic
      parameters. Statistical analysis was done using Wilcoxon's signed-rank test and
      Wilcoxon's two-sample test. RESULTS: Continence improved in eight patients.
      Differences among clinical, manometric, and radiologic data were not
      statistically significant. CONCLUSION: Pelvic floor repair procedures produce no
      consistent changes in anatomy or physiology. Clinical improvement is caused by
      creation of a local stenosis or by the placebo effect rather than by improvement
      of muscle function.

PMID- 9514435
TI  - Effects of preoperative fractionated irradiation on left colonic anastomoses in
      the rat.
AB  - PURPOSE: Radiotherapy is frequently used as a (neo)adjuvant to surgery in
      colorectal cancer patients, and because such therapy could influence the
      integrity of the anastomosis, we decided to investigate the effect of
      preoperative irradiation on colonic anastomosis. METHODS: Seventy-two male Wistar
      rats, weighing 200 to 348 g, were divided into three groups: a control group (I)
      underwent left colon resection and primary anastomosis (n = 20); a sham
      irradiated group (II, n = 20); a study group (III) that received fractionated
      irradiation to the whole pelvis (anterior-posterior pelvic field), for a total
      dose of 22 Gy, 5.5 Gy per fraction, on four consecutive days with linear
      accelerator (n = 32). Four days after irradiation, both Groups II and III
      underwent the same operation as performed in Group I. Within each group, one-half
      of the animals were anesthetized on the third postoperative day and one-half on
      the seventh postoperative day. Abdominal wound-healing, anastomotic
      complications, and anastomotic bursting pressure measurements were recorded.
      Following these measurements, the anastomotic segment was resected for
      hydroxyproline content and myeloperoxidase activity. RESULTS: Irradiated animals
      had more pronounced weight loss during therapy. There were no differences with
      abdominal wound-healing, intraperitoneal adhesions, and anastomotic complications
      between groups. At days 3 and 7, mean bursting pressures of the anastomosis were
      determined at 36.5 and 208 mmHg in Group I, 34.5 and 228 mmHg in Group II, and 25
      and 150 mmHg in Group III, respectively (P < 0.01 Group III vs. both Groups I and
      II on days 3 and 7). The burst occurred at the anastomosis in all animals tested
      on the third postoperative day and one in Group I (10 percent), none in Group II,
      and six in Group III (37.5 percent) on the seventh postoperative day. In
      addition, hydroxyproline content and myeloperoxidase activity was significantly
      lower in Group III. CONCLUSION: Although preoperative fractionated irradiation
      significantly decreased the anastomotic bursting pressure and more burst occurred
      in the anastomotic line on postoperative day 7, the clinical outcome was similar
      among the groups.

PMID- 9514436
TI  - Nifedipine and verapamil inhibit the sigmoid colon myoelectric response to eating
      in healthy volunteers.
AB  - BACKGROUND: Constipation is not an infrequent side effect complained of by
      patients taking calcium channel blockers. This effect may reduce patients'
      compliance and yield potentially serious consequences. However, the underlying
      mechanisms for constipation caused by such compounds are not known. AIMS: The
      purpose of the present study was to assess the effects of nifedipine and
      verapamil on the sigmoid myoelectric response to eating, a physiologic test of
      colonic motor function. SUBJECTS AND METHODS: Nine healthy male volunteers with
      no previous abdominal surgery were recruited for the study and underwent three
      paired studies at two-week intervals. Myoelectric sigmoid activity was recorded
      by means of two clip electrodes introduced within the viscus without preparation
      for 30 minutes basally and 90 minutes postprandially. Each study was preceded by
      placebo, nifedipine (20 mg), or verapamil (120 mg). RESULTS: Analysis of the
      tracings revealed that nifedipine strongly inhibited the sigmoid myoelectric
      response to the meal. This response was also significantly reduced in those
      taking verapamil compared with the placebo group, although to a much lesser
      extent than in those taking nifedipine. CONCLUSIONS: We conclude that
      constipation as a result of some calcium channel blockers may be caused by
      inhibition of colonic motor activity by nifedipine and, to a lesser extent, by
      verapamil. The latter compound probably displays other mechanisms (reduced
      colonic transit, increased water absorption) also responsible for this side
      effect.

PMID- 9514437
TI  - Nonresective alternative for the cure of nongangrenous sigmoid volvulus.
AB  - PURPOSE: Recurrence in sigmoid colon volvulus is a very vexing problem, because
      it occurs after all types of treatment including a resection of the sigmoid. A
      nonresective procedure that prevents recurrence in the long term has been devised
      and tried during the period 1968 to 1992. METHODS: The procedure involves
      extraperitonealization of the whole sigmoid colon via a left paracolic gutter
      incision in a manner akin to an extraperitonealized colostomy and placing it in
      the left half of the infraumbilical abdominal wall. This article presents a study
      of 84 patients who underwent this operation and who were followed-up. Some very
      useful practical points for ensuring the success of the procedure are also
      presented. RESULTS: The subjects comprised 58 male and 26 female patients, aged
      10 to 81 (median, 60) years. The operating time ranged from 40 to 70 (median, 50)
      min. The operative mortality (9 percent) and morbidity of the procedure including
      cardiopulmonary complications (7 percent), incidence of small-bowel obstruction
      (1 percent), and incisional hernia formation (2.3 percent), were reasonably low.
      The incidence of wound-healing problems was significantly (P < 0.02) reduced in
      the 1980s and 1990s. Seventy-six patients were available for follow-up ranging
      from 0.5 to 25 (mean+/-standard error, 6.671+/-0.573; median, 6) years. Forty
      eight patients were followed-up for five or more years. No patients developed
      recurrence of volvulus during the entire follow-up period. CONCLUSIONS: This
      nonresective, recurrence-free procedure provides a cure for nongangrenous sigmoid
      volvulus. It may be performed safely, even in relatively poor-risk patients, with
      acceptably low morbidity and mortality rates.

PMID- 9514438
TI  - Pelvic floor herniation after modified York-Mason approach to the rectum: report
      of a case.
AB  - The York-Mason approach to the rectum with resection of the coccyx provides an
      excellent exposure for the treatment of large villous adenomas and low-risk
      rectal cancers. Morbidity related to this operation primarily arises as local
      infection (septic pelvis, fistulation), chronic coccygeal pain, and fecal
      incontinence. This is the first report to describe a pelvic floor herniation two
      years after a York-Mason approach to the rectum.

PMID- 9514439
TI  - Computed tomographic angiography with three-dimensional reconstruction in
      patients with complex diverticular disease and portal hypertension: report of a
      case.
AB  - We report a case of a patient with portal hypertension secondary to alcoholic
      cirrhosis (Child's Class C) who initially presented with a colovaginal fistula
      secondary to acute sigmoid diverticulitis. The patient had a prior history of
      hepatic cirrhosis with ascites, coagulopathy, and portal hypertension. Computed
      tomography of the abdomen and pelvis demonstrated a large diverticular phlegmon
      and ascites. Computed tomographic angiography demonstrated a large left anterior
      abdominal wall varix in the region of the anticipated sigmoid resection. Three
      dimensional reconstruction of the computed tomographic angiography further
      delineated the path of this large varix, confirming the increased risk from
      surgical intervention. Following initial conservative treatment with intravenous
      antibiotics, parenteral nutrition, and percutaneous abscess drainage, a
      transjugular intrahepatic portosystemic shunt procedure was performed to
      decompress the portal system varices. A repeat computed tomographic scan with
      three-dimensional reconstruction confirmed decompression of the varix. A
      successful sigmoid resection was subsequently performed. Preoperative computed
      tomographic angiography with three-dimensional reconstruction is a useful adjunct
      in planning the operative strategy in patients with complex intraabdominal
      pathology and collateral portovenous flow secondary to portal hypertension.

PMID- 9514440
TI  - Pouch excision for recurrent serrated adenomas following restorative
      proctocolectomy for juvenile polyposis: report of a case.
AB  - PURPOSE: The study contained herein was undertaken to report the case of a
      patient with juvenile polyposis in whom multiple and rapid recurrence of mixed
      polyps, with progressive predominance of the adenomatous component, developed in
      a diverted ileoanal pouch. METHODS: The case of this patient with juvenile
      polyposis was reviewed. Despite regular surveillance and polypectomies, extensive
      and multiple recurrences of serrated polyps developed. RESULTS: Because the pouch
      was never cleared of polyps, a compromise to remove the pouch was decided on.
      Such a case has not been reported previously. CONCLUSION: Mixed juvenile
      polyposis may affect any level of the gastrointestinal tract. The ileal pouch and
      any rectal remnant may incidentally need surgical excision.

PMID- 9514441
TI  - Laparoscopic or open appendectomy? Critical review of randomized, controlled
      trials.
AB  - PURPOSE: A randomized, controlled trial is considered to be the "gold standard"
      to evaluate a new procedure. Thus, this critical review assessed whether the
      published randomized trials on laparoscopic appendectomy show that it is superior
      to the open approach. METHODS: Twelve original articles involving a randomized,
      controlled trial on laparoscopic appendectomy in adults published between January
      1990 and December 1996 were selected. We studied first whether each trial was
      positive (a procedure is superior to the other) or negative (no difference). We
      reviewed for each trial the methodology used and the following outcomes:
      operating time, intraoperative and postoperative complications, time until
      resumption of diet, postoperative pain, hospital stay, cost, and quality of life
      analyses. Postoperative morbidity was considered as the major primary outcome.
      RESULTS: There were six positive and six negative trials. Postoperative
      complication rates were similar, but the two approaches had specific potential
      complications, wound infections following open appendectomy, and intra-abdominal
      abscesses following laparoscopic appendectomy. This review failed to show a
      superiority of the laparoscopy for the other outcomes, particularly postoperative
      pain. CONCLUSION: Differences in positive trials concerned subjective and
      controversial outcomes, and the flaw in negative trials was their lack of power.
      Thus, nothing is definitively well established, even after 12 randomized trials.

PMID- 9514442
TI  - Is a restorative proctocolectomy compatible with active military service?

PMID- 9514443
TI  - Anal continence after surgery for rectal prolapse.

PMID- 9514444
TI  - Pudendal canal syndrome and proctalgia fugax: a mechanism creating pain.

PMID- 9514445
TI  - Dyslipidemias have a detrimental effect on left ventricular systolic function in
      patients with a first acute myocardial infarction.
AB  - Several large-scale clinical trials have shown that lipid-lowering interventions
      are associated with reduced coronary events and mortality. However, whether
      dyslipidemias have a detrimental effect on the evolution of myocardial infarction
      (MI) is still unknown. To examine whether dyslipidemias can aggravate myocardial
      vulnerability following MI, 165 patients with a first MI were studied. All
      patients underwent measurements of serum lipid profiles 1 week and 3 months after
      MI, a radionuclide ventriculographic study, and a coronary angiographic study.
      The patients were divided into 3 groups according to their 3-month serum
      cholesterol levels (group 1, <200 mg/dl; group 2, 200 to 240 mg/dl; group 3, >240
      mg/dl). Groups 1, 2, and 3 consisted of 66, 59, and 40 patients, respectively.
      Group 3 had a higher Gensini score than groups 1 and 2, although this was not
      statistically significant (p = 0.13). The postinfarct left ventricular ejection
      fraction (LVEF) was highest in group 1 (53 +/- 13%), at mid level in group 2 (43
      +/- 14%), and lowest in group 3 (35 +/- 11%) (p < 0.0001). A significant negative
      correlation between 3-month low-density lipoprotein (LDL) cholesterol (r = -0.55,
      p < 0.0001) and the postinfarct LVEF was found. The product of peak creatine
      kinase (CK(MAX)) and time to CK(MAX) (p = 0.001), and patency of the infarct
      related artery (p = 0.009), rather than variables of coronary atherosclerosis,
      were also independent predictors of the postinfarct LVEF. Increases in 1-week LDL
      cholesterol and decreases in 1-week high-density lipoprotein cholesterol were
      associated with a higher CK(MAX) and a lower patency rate of the infarct-related
      artery, respectively. This study revealed that dyslipidemias per se, especially
      LDL cholesterol, had a detrimental effect on the postinfarct LVEF; this effect
      might be independent of the atherogenic properties of dyslipidemias.

PMID- 9514446
TI  - Comparison of different echocardiographic methods with radionuclide imaging for
      measuring left ventricular ejection fraction during acute myocardial infarction
      treated by thrombolytic therapy.
AB  - The aim of this study was to: (1) compare the usefulness, in clinical practice,
      of different echocardiographic methods of left ventricular (LV) function
      determination in patients with a recent thrombolytic-treated acute myocardial
      infarction (AMI); (2) compare these measurements with the reference method
      radionuclide imaging; and (3) evaluate the reproducibility of visual estimation
      of the LV ejection fraction (EF) and the use of the biplane method of discs
      (Simpson's rule) in clinical practice. Echocardiography and radionuclide imaging
      were performed within 2 hours of each another, 5 to 8 days after hospital
      admission. Ninety-six patients (70 men and 26 women) age 64 +/- 9 years (range 45
      to 75) were studied. The echocardiographic study was performed by 2 experienced
      physicians, independently of each another. LV wall motion score index and visual
      estimation of the EF correlated best with the radionuclide EF (r = 0.72 and r =
      0.71), thereafter simply counting the number of affected LV segments (r = 0.67)
      or atrioventricular plane measurements (r = 0.64). Simpson's rule had low
      correlation to the radionuclide EF (r = 0.45 to 0.51) and could not be used in
      approximately half of the patients due to poor identification of endocardial
      borders. The interobserver coefficient of variation for independent visual
      echocardiographic estimation of the EF was 10%, for Simpson's rule 18%, and for
      the radionuclide EF 5%. We conclude that the EF estimated from quantitative
      echocardiographic volume calculations (Simpson's rule) may differ substantially
      from radionuclide methods of measuring the EF. However, with experienced
      sonographers, the LV wall motion score index or visual estimation of the EF had
      reasonable agreement with the radionuclide EF in most of the patients.
      Atrioventricular plane measurement is an acceptable alternative.

PMID- 9514447
TI  - Prognostic value of stress echocardiography in the evaluation of atypical chest
      pain patients without known coronary artery disease.
AB  - Patients with atypical chest pain frequently lack significant coronary artery
      disease (CAD) and are, therefore, at low risk for future adverse cardiovascular
      events. We hypothesized that in this group of patients, stress echocardiography
      could identify those at risk for cardiac events. We retrospectively reviewed
      (mean follow-up 23.0 +/- 7.2 months) the prognostic value of stress
      echocardiography for major (cardiac death, myocardial infarction, congestive
      heart failure, and unstable angina) and total (major events plus coronary
      revascularization) cardiac events in 661 patients with atypical chest pain,
      normal global left ventricular (LV) systolic function, and no history of CAD. A
      positive stress echocardiogram was defined as the development of new or worsening
      wall motion abnormalities with exercise stress (80%) or dobutamine (20%). A total
      of 41 cardiac and 16 major events were noted. The event-free survival for total
      cardiac events was 97% for a normal stress echocardiogram and 93% for a normal
      stress electrocardiogram (ECG) at 30 months. A positive stress ECG predicted an
      event-free rate of 86% compared with 74% for stress-induced wall motion
      abnormalities and 42% if stress-induced LV dysfunction accompanied the wall
      motion abnormalities. A strategy recommending invasive studies based on positive
      stress echocardiogram results increased the per-patient cost, but led to greater
      savings per cardiac event predicted and provided incremental prognostic value for
      future cardiac events beyond clinical and stress electrocardiographic data. Thus,
      stress echocardiography in low-risk patients for CAD appears to be more cost
      effective than a stress ECG.

PMID- 9514448
TI  - Comparative early and nine-month results of rotational atherectomy, stents, and
      the combination of both for calcified lesions in large coronary arteries.
AB  - The aim of this study was to determine the preferred treatment modality for
      calcified lesions in large (> or = 3 mm) coronary arteries, resulting in the
      largest lumen dimensions and the most favorable late clinical responses. Three
      hundred six lesions in 306 patients (223 men, mean age 66 +/- 11 years) were
      treated with either rotational atherectomy plus adjunct balloon angioplasty (n =
      147), Palmaz-Schatz stents (n = 103), or a combination of rotational atherectomy
      plus adjunct Palmaz-Schatz stents (n = 56). The procedural success rate was 98.0%
      to 98.6% for each treatment modality. Minimal lumen diameter (MLD) before therapy
      was similar for all therapies. Final MLD after combination of rotational
      atherectomy plus Palmaz-Schatz stents was larger than after stent therapy or
      rotational atherectomy plus balloon angioplasty (3.21 +/- 0.49 mm, 2.88 +/- 0.51
      mm, and 2.29 +/- 0.55 mm, respectively, p <0.0001). Correspondingly, final
      percent diameter stenosis was lowest after the combination of rotational
      atherectomy plus stent therapy, and significantly higher for stents or rotational
      atherectomy plus balloon angioplasty (4.2 +/- 15.3%, 14.1 +/- 13.3%, and 26.7% +/
      16.9%, respectively, p <0.0001). Event-free survival at 9 months was higher for
      patients treated with the combination of rotational atherectomy plus stents than
      either stent therapy or rotational atherectomy alone (85%, 77%, and 67%,
      respectively, log-rank p = 0.0633). The only significant independent predictor of
      an event during the 9-month follow-up period was the MLD after intervention (odds
      ratio 0.495, 95% confidence interval 0.308 to 0.796, p = 0.0037). We conclude
      that preatheroablation using rotational atherectomy, followed by adjunct stent
      placement for calcified lesions in large arteries, is associated with infrequent
      complications, the largest acute angiographic results, and the most favorable
      late clinical event rates.

PMID- 9514449
TI  - Significance of coronary artery bypass grafting-associated conduction defects.
AB  - The incidence of permanent atrioventricular conduction defects (CDs) caused by
      coronary artery bypass grafting (CABG) varies from 5% to 43% if cold crystalloid
      or blood cardioplegia is used for myocardial preservation. However, the long-term
      effects of CDs on clinical outcome are not well known. In this study we compared
      the outcome of 52 patients with permanent CABG-associated CDs (CD+) to 47
      patients without CDs (CD-) after a 3-year follow-up. Recovery of CDs was found in
      2 patients during the follow-up. There were no significant differences between
      groups in late mortality, cardiac or neurologic events, or capability to work.
      Although exercise capacity was similar, the exercise-limiting symptom more often
      was chest pain or dyspnea in the CD+ group than in the CD- group (p = 0.001).
      Left ventricular ejection fractions at rest and at 50-W workload level were lower
      in the CD+ group (p = 0.03 to 0.05). In addition, CD+ patients with left bundle
      branch block or cardiac pacemaker had significantly lower ejection fraction at
      maximal workload level than patients without CDs (p = 0.03). No significant
      differences were observed between the groups in the potential risk for
      ventricular arrhythmias according to signal-averaged electrocardiograms. In
      conclusion, the clinical outcome of patients with CDs after CABG operations is
      almost comparable to those without CDs during a 3-year follow-up. However,
      patients with CDs have lower left ventricular systolic function and more often
      have chest pain or dyspnea as the exercise-limiting symptom than patients without
      CDs.

PMID- 9514450
TI  - Relation between QT dispersion and the extent of myocardial ischemia in patients
      with three-vessel coronary artery disease.
AB  - The aim of the study was to examine the relation between the extent of myocardial
      ischemia and changes in QT interval dispersion in patients with obstructive
      coronary artery disease and in patients with normal coronary arteries. QT
      interval dispersion reflects regional variations in ventricular repolarization
      and cardiac electrical instability. Previous studies showed QT interval
      dispersion changes during episodes of myocardial ischemia in patients with
      coronary artery disease, but no data on the relation between extent of myocardial
      ischemia and degree of QT interval dispersion changes are available. To assess
      the effects of myocardial ischemia on myocardial repolarization by analyzing the
      change in QT dispersion during incremental atrial pacing, we studied 33 patients
      (7 women and 26 men, mean age 60.1 +/- 5.1 years, 18 patients with normal
      coronary arteries, 15 patients with coronary 3-vessel disease). QT dispersion was
      measured at baseline, after each pacing period, within 30 seconds after cessation
      of pacing ("peak ischemic stress"), and at 1-minute intervals for up to 5
      minutes. Paired blood samples for determination of serum lactate were withdrawn
      from the coronary sinus and radial artery to determine the cardiac lactate
      extraction ratio at each point of electrocardiographic registration. In patients
      with coronary artery disease, QT dispersion increased from a baseline value of 39
      +/- 7 ms to a peak ischemic stress value of 63 +/- 10 ms (p <0.0001). Patients
      with normal coronary arteries showed almost unchanged values of QT dispersion (41
      +/- 9 vs 42 +/- 7 ms). There was a significant relation between the pacing
      induced change in QT dispersion and the induced change in myocardial lactate
      extraction ratio (r = 0.76, p <0.0001). The change in QT dispersion (baseline vs
      peak pacing stress) was related to the extent of the cardiac lactate extraction
      ratio (r = -0.79, p <0.0001). These data indicate that the severity or extent of
      induced myocardial ischemia was related to the degree of induced changes of the
      variability in the timing of the ventricular recovery pattern.

PMID- 9514451
TI  - Efficacy and safety of a hemostatic puncture closure device with early ambulation
      after coronary angiography. Angio-Seal Investigators.
AB  - A collagen hemostatic puncture closure device has been developed as an
      alternative to traditional manual pressure techniques for achieving effective
      femoral arterial hemostasis after coronary angiography. The purpose of the
      current study was to determine if patients receiving this device can ambulate
      safely at 1 hour compared with patients receiving traditional manual pressure and
      bed rest after sheath removal for diagnostic cardiac catheterization. Patients (n
      = 304) were randomized to either the device group (n = 202) with ambulation at 1
      hour after sheath removal or to the manual pressure control group (n = 102) with
      ambulation at 4 to 6 hours after sheath removal. The device group achieved
      earlier time to hemostasis (0.9 +/- 3 vs 17.0 +/- 8 minutes, p = 0.0001) and
      faster time to outpatient discharge (5.0 +/- 4 vs 7.7 +/- 4 hours, p = 0.0001)
      compared with the control group. There were bleeding or vascular complications in
      19 patients (9%) in the device group and in 6 patients (6%) in the manual
      pressure group (p = 0.397). In patients undergoing diagnostic coronary
      angiography, this device, compared with traditional techniques for achieving
      hemostasis after sheath removal, allows for faster time to effective hemostasis
      with resultant earlier discharge from the hospital.

PMID- 9514452
TI  - Detection of coronary vasospasm by posthyperventilation technetium-99m sestamibi
      single-photon emission computed tomography imaging in patients with coronary
      artery disease.
AB  - Forced hyperventilation is simple, safe to perform, and can be used as a
      provocative test for coronary vasospasm. This study assesses whether a
      vasospastic component of angina might be detected in patients with
      angiographically "nonobstructive" coronary artery disease by posthyperventilation
      technetium-99m (Tc-99m) sestamibi single-photon emission computed tomography
      (SPECT) cardiac imaging. Eleven patients with angiographically nonobstructive
      coronary artery disease underwent Tc-99m sestamibi SPECT imaging at rest and
      after forced hyperventilation. Vessel diameters were measured by quantitative
      angiography before and after forced hyperventilation, and posthyperventilation
      SPECT images were compared with dipyridamole Tc-99m sestamibi stress images.
      Forced hyperventilation resulted in a 15% reduction in coronary artery diameter
      in stenotic segments (p <0.01), and a 17% reduction in adjacent nonstenotic
      segments (p <0.001). Myocardial uptake of Tc-99m sestamibi in segments perfused
      by vessels with angiographically nonobstructive stenoses was reduced by 24%
      following forced hyperventilation (p <0.001) compared with only 4% following
      dipyridamole (p <0.02). These findings suggest that posthyperventilation Tc-99m
      sestamibi SPECT imaging in patients with angina pectoris and nonobstructive
      coronary artery disease may be useful in identifying a vasospastic component of
      angina.

PMID- 9514453
TI  - Rationale and design of the Myocardial Ischemia Reduction with Aggressive
      Cholesterol Lowering (MIRACL) study that evaluates atorvastatin in unstable
      angina pectoris and in non-Q-wave acute myocardial infarction.
AB  - The goal of the Myocardial Ischemia Reduction with Aggressive Cholesterol
      Lowering (MIRACL) study is to determine whether early, rapid, and profound
      cholesterol lowering therapy with atorvastatin can reduce early recurrent
      ischemic events in patients with unstable angina or non-Q-wave acute myocardial
      infarction. Within 1 to 4 days of hospitalization for one of these conditions,
      2,100 patients will be randomly assigned to receive atorvastatin, 80 mg/day, or
      placebo in a double-blind design. Both groups receive dietary counseling. Over a
      16-week follow-up period, the primary outcome measure is the time to occurrence
      of an ischemic event, defined as death, nonfatal acute myocardial infarction,
      cardiac arrest with resuscitation, or recurrent symptomatic myocardial ischemia
      requiring emergency rehospitalization. Secondary outcome measures are the time to
      occurrence and incidence of each of the primary outcome components, as well as
      nonfatal stroke, worsening angina, congestive heart failure requiring
      hospitalization, and need for coronary revascularization not anticipated before
      randomization. The sample size of 1,050 patients in each group is expected to
      provide 95% power to detect a 30% reduction in the primary outcome measure with a
      5% level of significance. The results of the MIRACL study will determine the
      utility of profound cholesterol lowering as an early intervention in acute
      coronary syndromes.

PMID- 9514454
TI  - Comparative dose efficacy study of atorvastatin versus simvastatin, pravastatin,
      lovastatin, and fluvastatin in patients with hypercholesterolemia (the CURVES
      study)
AB  - The objective of this multicenter, randomized, open-label, parallel-group, 8-week
      study was to evaluate the comparative dose efficacy of the 3-hydroxy-3
      methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor atorvastatin 10, 20, 40,
      and 80 mg compared with simvastatin 10, 20, and 40 mg, pravastatin 10, 20, and 40
      mg, lovastatin 20, 40, and 80 mg, and fluvastatin 20 and 40 mg. Investigators
      enrolled 534 hypercholesterolemic patients (low-density lipoprotein [LDL]
      cholesterol > or = 160 mg/dl [4.2 mmol/L] and triglycerides < or = 400 mg/dl [4.5
      mmol/L]). The efficacy end points were mean percent change in plasma LDL
      cholesterol (primary), total cholesterol, triglycerides, and high-density
      lipoprotein cholesterol concentrations from baseline to the end of treatment
      (week 8). Atorvastatin 10, 20, and 40 mg produced greater (p < or = 0.01)
      reductions in LDL cholesterol, -38%, -46%, and -51%, respectively, than the
      milligram equivalent doses of simvastatin, pravastatin, lovastatin, and
      fluvastatin. Atorvastatin 10 mg produced LDL cholesterol reductions comparable to
      or greater than (p < or = 0.02) simvastatin 10, 20, and 40 mg, pravastatin 10,
      20, and 40 mg, lovastatin 20 and 40 mg, and fluvastatin 20 and 40 mg.
      Atorvastatin 10, 20, and 40 mg produced greater (p < or = 0.01) reductions in
      total cholesterol than the milligram equivalent doses of simvastatin,
      pravastatin, lovastatin, and fluvastatin. All reductase inhibitors studied had
      similar tolerability. There were no incidences of persistent elevations in serum
      transaminases or myositis.

PMID- 9514455
TI  - Antiarrhythmic drug effects on QT interval dispersion in patients undergoing
      electropharmacologic testing for ventricular tachycardia and fibrillation.
AB  - The effects of antiarrhythmic drugs on QT interval dispersion as a predictor of
      antiarrhythmic drug therapy has not been rigorously assessed. This study was
      performed to determine whether the effects of antiarrhythmic drugs on QT interval
      dispersion predict antiarrhythmic drug response in patients undergoing
      electropharmacologic testing for ventricular tachycardiarrythmias. Precordial QT
      intervals and QT interval dispersions were measured at baseline and during steady
      state antiarrhythmic drug therapy in 72 consecutive patients with documented
      coronary artery disease and remote myocardial infarction presenting with
      spontaneous sustained ventricular tachyarrhythmias who underwent
      electropharmacologic studies to assess arrhythmia suppression. QT interval
      dispersion was similar at baseline in drug responders (42 +/- 21 ms) and drug
      nonresponders (46 +/- 21 ms), whereas during antiarrhythmic therapy QT interval
      dispersion was shorter in drug responders (33 +/- 15 ms) than in drug
      nonresponders (55 +/- 29 ms, p <0.001). QT interval dispersion was shorter in 7
      drug responders during their effective drug trials (27 +/- 14 ms) than during
      their ineffective drug trials (47 +/- 24 ms, n = 9, p <0.05). QT dispersion < or
      = 50 ms (p <0.002) and a patent infarct-related artery (p <0.003) were
      independent predictors of antiarrhythmic therapy. The positive and negative
      predictive value of QT interval dispersion during drug therapy to predict a
      successful drug response was 32% and 96%, respectively. QT interval dispersion
      predicted the outcome of electropharmacologic studies independent of infarct
      related artery patency. QT interval dispersion >50 ms during drug therapy was
      associated with ineffective drug therapy.

PMID- 9514456
TI  - Intravenous amiodarone for acute heart rate control in the critically ill patient
      with atrial tachyarrhythmias.
AB  - Control of heart rate in critically ill patients who develop atrial fibrillation
      or atrial flutter can be difficult. Amiodarone may be an alternative agent for
      heart rate control if conventional measures are ineffective. We retrospectively
      studied intensive care unit patients (n = 38) who received intravenous amiodarone
      for heart rate control in the setting of hemodynamically destabilizing atrial
      tachyarrhythmias resistant to conventional heart rate control measures. Atrial
      fibrillation was present in 33 patients and atrial flutter in 5 patients. Onset
      of rapid heart rate (mean 149 +/- 13 beats/min) was associated with a decrease in
      systolic blood pressure of 20 +/- 5 mm Hg (p <0.05). Intravenous diltiazem (n =
      34), esmolol (n = 4), or digoxin (n = 24) had no effect on heart rate, while
      reducing systolic blood pressure by 6 +/- 4 mm Hg (p <0.05). The infusion of
      amiodarone (242 +/- 137 mg over 1 hour) was associated with a decrease in heart
      rate by 37 +/- 8 beats/min and an increase in systolic blood pressure of 24 +/- 6
      mm Hg. Both of these changes were significantly improved (p <0.05) from onset of
      rapid heart rate or during conventional therapy. Beneficial changes were also
      noted in pulmonary artery occlusive pressure and cardiac output. There were no
      adverse effects secondary to amiodarone therapy. Intravenous amiodarone is
      efficacious and hemodynamically well tolerated in the acute control of heart rote
      in critically ill patients who develop atrial tachyarrhythmias with rapid
      ventricular response refractory to conventional treatment. Cardiac
      electrophysiologic consultation should be obtained before using intravenous
      amiodarone for this purpose.

PMID- 9514457
TI  - Hemodynamic performance of the 21-mm St. Jude BioImplant prosthesis using
      dobutamine Doppler echocardiography.
AB  - This study examines the hemodynamic performance of small size St. Jude BioImplant
      aortic prostheses using dobutamine echocardiography. Eleven patients (3 women,
      mean age 75 years) who had undergone aortic valve replacement with a size 21-mm
      St. Jude BioImplant aortic prostheses at 10.8 +/- 5.1 months (SD) previously were
      studied. Dobutamine infusion was started at a rate of 5 microg/kg/min and
      increased to 10 microg/kg/min, and subsequently to 20 microg/kg/min at 15-minute
      intervals. Pulsed and continuous-wave Doppler studies were performed at rest and
      at the end of each stage. Effective orifice area, mean gradient, and the
      performance index across each prosthesis were calculated and cardiac output was
      determined by Doppler measurement of flow in the left ventricular outflow tract.
      Stress dobutamine increased heart rate and cardiac output by 51% and 56%,
      respectively (both p <0.0001), and the mean transvalvular gradient increased from
      30.1 +/- 7.5 mm Hg at rest to 49.3 +/- 11.5 mm Hg at maximum stress (p <0.0005).
      The performance index increased progressively from 0.29 +/- 0.05 at rest to 0.40
      +/- 0.10 at maximum stress (p <0.0005). Regression modeling analyses demonstrated
      that the maximum stress gradient was independent of all variables except the
      resting gradient (p = 0.03). Body surface area had no effect on the changes in
      cardiac output, effective orifice area, or transprosthetic gradient at maximum
      stress. Thus, these data demonstrate that the size 21-mm St. Jude BioImplant
      prosthesis exhibits suboptimal hemodynamic performance with transvalvular
      gradients consistent with mild to moderate aortic stenosis, both at rest and
      under stress conditions.

PMID- 9514458
TI  - Levels of circulating adhesion molecules in congestive heart failure and after
      heart transplantation.
AB  - Recent reports suggest a role for immunologic and inflammatory processes in the
      pathogenesis of congestive heart failure (CHF) and accelerated coronary artery
      disease (CAD) after heart transplantation (HT). The interaction between
      endothelial cells, leukocytes, and platelets involving various adhesion molecules
      may be of particular importance. We therefore measured serum levels of soluble(s)
      vascular cell adhesion molecule-1 (VCAM-1), sP-selectin, and sE-selectin in 34
      patients with severe CHF (23 with CAD and 11 with idiopathic dilated
      cardiomyopathy) and in 20 healthy controls. Twenty of the patients were followed
      with serial measurements of these circulating adhesion molecules (CAMs) for up to
      2 years after HT. Levels of all 3 CAMs were significantly elevated in patients
      with CHF compared with controls irrespective of the etiology of heart failure,
      with particularly high concentrations of sVCAM-1. After HT, different patterns in
      CAMs were found over time. Whereas there was a normalization of sE-selectin
      levels after HT, concentrations of sVCAM-1 also declined, but without
      normalization. In contrast, sP-selectin levels were persistently elevated, with
      the highest concentrations at the end of the study period. The persistent
      elevation of sP-selectin and the lack of normalization of sVCAM-1 levels were
      associated with persistently raised serum levels of tumor necrosis factor-alpha,
      and these findings were not related to either acute episodes of allograft
      rejection or intercurrent infections. These results support the notion that
      immunologic and inflammatory processes are important features of CHF.
      Furthermore, the persistently elevated levels of CAMs and tumor necrosis factor
      alpha found up to 2 years after HT may reflect a state of persistent immune
      activation in these patients, possibly involved in the development of CAD after
      HT.

PMID- 9514459
TI  - Contraction and relaxation velocities of the normal left ventricle using pulsed
      wave tissue Doppler echocardiography.
AB  - We designed the present study (1) to investigate the velocities of longitudinal
      movement of the human left ventricle by pulsed-wave tissue Doppler (PWTD)
      imaging; (2) to test the hypothesis that a heterogeneous pattern of longitudinal
      systolic and diastolic velocities exists among individual left ventricular wall
      segments; (3) to establish the range of this heterogeneity, and (4) to correlate
      the function of individual segments with the known orientation of myocardial
      fibers. PWTD is a novel ultrasound method to quantify myocardial contraction and
      relaxation velocities. In 27 young normal subjects, PWTD peak values of
      longitudinal systolic and diastolic velocities were measured for 12 left
      ventricular segments visualized from the apical window. The PWTD sampling of each
      myocardial segment resulted in a triphasic velocity curve during each cardiac
      cycle: a systolic velocity wave (S) directed toward the transducer, and an early
      diastolic (E) and a late diastolic (A) velocity wave away from the transducer. A
      heterogeneous pattern of systolic and diastolic myocardial velocities was
      observed between individual wall segments as well as for the basal and
      midsegments of each myocardial wall. The difference between the highest and
      lowest values for S was 38.4% in the basal segments and 56.3% in the midwall
      segments. The difference between low and high velocities for E was 61.4% in the
      basal and 38.2% in the midsegments; for A the difference was 29.5% in the basal
      and 32.6% in the midsegments. In general, lower velocity values were found in the
      septum with higher basal to midwall difference. The lateral and posterior walls
      had higher, but more uniform, velocities. PWTD enables the quantitative
      assessment of regional systolic and diastolic myocardial velocities. Substantial
      heterogeneity of velocities exists within individual myocardial segments, and
      must be taken into account in any clinical application. The observed
      heterogeneity in longitudinal function is consistent with the known spatial
      distribution of myocardial fibers.

PMID- 9514460
TI  - Quantification of the myocardial response to low-dose dobutamine using tissue
      Doppler echocardiographic measures of velocity and velocity gradient.
AB  - Low-dose dobutamine echocardiography has been clinically useful in myocardial
      viability studies, although routine visual assessment of wall motion is
      subjective. The objective was to quantify the incremental myocardial response to
      low-dose dobutamine infusion using a new semiautomated tissue Doppler (TD)
      analysis system and to compare these data with routine echocardiographic measures
      in the same subjects. Twelve subjects had TD and routine echocardiographic
      studies at baseline and during 10-minute stages of dobutamine infusion at 1, 2,
      3, and 5 microg/kg/min. Color TD video data were converted to a digital velocity
      matrix (4.5 velocity data points/mm at 500 Hz) for analysis of mitral annular
      velocity, endocardial velocity, and velocity gradient at each stage. Posterior
      wall percent thickening and ejection fraction were calculated from the routine
      images. Mitral annular peak systolic velocity significantly increased with only 1
      microg/kg/min of dobutamine from 69 +/- 9 to 77 +/- 7 mm/s (p <0.05 vs baseline),
      and further incremental increases occurred with each subsequent dose.
      Anteroseptal and posterior wall peak endocardial velocity increased with 2
      microg/kg/min of dobutamine from 33 +/- 7 to 46 +/- 15 mm/s and 50 +/- 9 to 61 +/
      10 mm/s, respectively (p <0.01 vs baseline) and further increased with 5
      microg/kg/min (p <0.0001 vs 3 microg/kg/min). Posterior wall peak systolic
      gradient also increased with 2 microg/kg/min of dobutamine from 3.1 +/- 0.6 to
      5.4 +/- 1.6 s(-1) (p <0.05 vs baseline). Routine measures of percent wall
      thickening or ejection fraction did not detect increases until the 3
      microg/kg/min dose. TD can detect subtle alterations in contractility induced by
      low-dose dobutamine and has the potential to quantify regional ventricular
      function objectively.

PMID- 9514461
TI  - Percutaneous balloon mitral valvuloplasty by the Inoue balloon technique: the
      procedure of choice for treatment of mitral stenosis.
AB  - The Inoue technique of percutaneous balloon mitral valvuloplasty, introduced in
      1984, is a truly startling advance in cardiology in modern times. It is time to
      reeducate our colleagues that when they hear the opening snap in patients with
      mitral stenosis, they should automatically open these stenotic mitral valves with
      an Inoue balloon catheter rather than submit these patients to surgical
      correction.

PMID- 9514462
TI  - Circadian variation of myocardial ischemia in patients with unstable angina
      pectoris secondary to fixed and/or spastic coronary narrowing.
AB  - We investigated the circadian variation of myocardial ischemia in patients with
      unstable angina using a 24-hour 12-lead electrocardiographic monitoring system
      with computer analysis. The circadian variation of ischemic attacks in patients
      who had ST elevation showed a similarity to that of the onset of acute myocardial
      infarction and most of these patients had vasospasm without organic stenosis; no
      similarity was seen in patients with organic stenosis.

PMID- 9514464
TI  - One-year follow-up of recanalization of totally occluded aortocoronary saphenous
      vein grafts using transluminal extraction atherectomy.
AB  - Recanalization of totally occluded aortocoronary saphenous vein grafts with
      extraction atherectomy was successful in 80% of patients. Whereas all patients
      with unsuccessful procedures were dead at 1 year, 75% of those with successful
      procedures are alive and free of events.

PMID- 9514463
TI  - Aggressive lipid lowering in postcoronary angioplasty patients with elevated
      cholesterol (the Lovastatin Restenosis Trial).
AB  - A substudy of the Lovastatin Restenosis Trial in patients with elevated
      cholesterol (>200 mg/dl) showed no evidence of an effect of aggressive lipid
      lowering on restenosis, confirming the results of the main trial.

PMID- 9514465
TI  - Complications of acute myocardial infarction in patients > or = 90 years of age.
AB  - Forty consecutive 90-year-old persons with an acute myocardial infarction were
      studied to describe the noncardiac complications of their care. Common negative
      consequences of hospitalization of these patients included delirium, pressure
      ulcers, and poor ambulatory status at discharge.

PMID- 9514467
TI  - Left ventricular Doppler diastolic filling patterns in patients with isolated
      left bundle branch block.
AB  - To evaluate the effect of isolated left bundle branch block (LBBB) on diastolic
      filling patterns, we evaluated 14 subjects with isolated LBBB and 16 age- and sex
      matched healthy subjects with normal ventricular conduction by echocardiography.
      Maximum E-wave velocity, E/A ratio, deceleration time of E wave, and the slope of
      deceleration of the E wave were lower in subjects with LBBB compared with
      subjects with normal ventricular conduction. Doppler filling patterns were
      significantly altered in subjects with isolated LBBB.

PMID- 9514466
TI  - Safety of intracoronary ultrasound imaging in patients with acute myocardial
      infarction.
AB  - In 103 patients with acute myocardial infarction, intracoronary ultrasound
      imaging (ICUS) was performed before and after percutaneous transluminal coronary
      angioplasty (PTCA) with a pre-PTCA success rate of 79 of 103 patients (76.7%),
      post-PTCA rate of 88 of 103 patients (85.4%), and a reversible subacute occlusion
      rate after initial ICUS of 3.9%. Time consumption was 7 +/- 1 minute for pre-PTCA
      ICUS and 3 +/- 1 minute for post-PTCA ICUS.

PMID- 9514468
TI  - Limitation of long-term atrial pacing via floating ring electrode using
      overlapping biphasic impulse stimulation in ambulatory-paced patients.
AB  - Long-term atrial pacing with overlapping biphasic impulse stimulation using
      floating atrial electrodes is limited in its use by the high rate of intermittent
      failure to capture the atrium and by the occurrence of diaphragmatic stimulation
      in ambulatory patients.

PMID- 9514469
TI  - Comparison of frequency of new coronary events in older persons with mild,
      moderate, and severe valvular aortic stenosis with those without aortic stenosis.
AB  - Independent risk factors for new coronary events were prior myocardial
      infarction, valvular aortic stenosis, male gender, and increasing age in patients
      with aortic stenosis. In older persons with moderate or severe valvular aortic
      stenosis, congestive heart failure, syncope, or angina pectoris was present in
      101 of 114 persons (89%) with new coronary events and in 1 of 22 persons (5%)
      without new coronary events (p <0.0001).

PMID- 9514470
TI  - Reliability of the electrocardiogram for detecting left ventricular hypertrophy
      in the elderly.
AB  - In elderly people > or = 65 years old, QRS amplitudes in electrocardiograms
      correlated with left ventricular wall thickness, although the correlation
      decreased with advancing age. Simple voltage criteria for left ventricular
      hypertrophy are adequate, even in elderly people.

PMID- 9514471
TI  - Clinical comparison of acoustic and electronic stethoscopes and design of a new
      electronic stethoscope.
AB  - This clinical study was performed to evaluate the advantages and limitations of 3
      acoustic stethoscopes and 3 electronic stethoscopes. It shows that it is possible
      to design a new electronic stethoscope by considering the advantages of both the
      acoustic and electronic stethoscopes.

PMID- 9514472
TI  - Anterior mitral leaflet retraction--a new echocardiographic predictor of severe
      mitral regurgitation following balloon valvuloplasty by the Inoue technique.
AB  - Echocardiographic quantification of the severity of anterior mitral leaflet
      retraction aids prediction of severe mitral regurgitation after balloon
      valvuloplasty.

PMID- 9514473
TI  - Fewer hearts than earlier predicted.

PMID- 9514475
TI  - Pulsed Doppler tissue imaging.

PMID- 9514474
TI  - Severe mitral regurgitation late after healing of myocardial infarction from
      calcification of the posteromedial left ventricular papillary muscle.

PMID- 9514476
TI  - Lipid clinic versus nonlipid clinic.

PMID- 9514477
TI  - Effect of atrial fibrillation on outcome of percutaneous balloon mitral
      valvuloplasty.

PMID- 9514478
TI  - Endoscopic transthoracic sympathecotomy in angina pectoris.

PMID- 9514479
TI  - Aqueous humor uric acid and ascorbic acid concentrations and outcome of
      trabeculectomy.
AB  - OBJECTIVE: To determine if there is an association between the surgical outcome
      of trabeculectomy and uric acid and ascorbic acid concentrations in the aqueous
      humor at the time of the procedure. PATIENTS, MATERIALS, AND METHODS: Aqueous
      humor samples were collected from the eyes of 169 of 249 adult patients who
      underwent trabeculectomy alone for any type of glaucoma between April 1989 and
      July 1995. Postoperatively, all medical records were reviewed and outcomes were
      classified as successful, unsuccessful, or indeterminate. The ascorbic acid and
      uric acid concentrations were determined in masked fashion by high-pressure
      liquid chromatography. Factors associated with surgical outcome were determined.
      RESULTS: Uric acid concentration was higher in unsuccessful eyes (mean+/-SD,
      0.21+/-0.08 mmol/L, n=26) than in successful eyes (0.15+/-0.09 mmol/L, n=91, 95%
      confidence interval for difference, 0.02-0.10 mmol/L). Ascorbic acid levels were
      not significantly different in the eyes with unsuccessful (1129.9+/-601.9
      micromol/L) and successful (1334.3+/-511.0 micromol/L) surgery (95% confidence
      interval for difference, -475.2 to 66.4 micromol/L, P=.13) surgery. Other factors
      associated with failure were previous surgery and surgery performed at the
      inferior limbus. A multiple polytomous logistic regression analysis was
      performed, after excluding the small number of operations performed at the
      inferior limbus. The odds ratio for failure increased by a factor of 1.68 for
      every 1-mmol/L increase in uric acid (95% confidence interval, 1.16-2.43,
      P=.006). CONCLUSIONS: Uric acid levels were higher at the time of surgery in eyes
      that had unsuccessful outcomes than in those with successful outcomes. No
      significant difference in ascorbic acid levels was detectable. A higher uric acid
      level in the aqueous humor is a risk factor for trabeculectomy failure and might
      be tested as a prognostic indicator [corrected].

PMID- 9514480
TI  - Outcomes of primary trabeculectomy with the use of adjunctive mitomycin.
AB  - OBJECTIVE: To investigate the efficacy and safety of adjunctive mitomycin when
      used during a primary trabeculectomy within a series of 89 consecutive patients
      at 1 and 2 years postoperatively. DESIGN: A cohort study of all patients who
      underwent primary trabeculectomy, performed by one of us (P.F.P.), between April
      1, 1991, and December 31, 1994. Patients received topical mitomycin in
      conjunction with a corneal safety valve incision. A trabeculectomy was considered
      "successful" if it resulted in an intraocular pressure (IOP) of 21 mm Hg or lower
      and a 30% or greater reduction in the IOP at and after 1 year of follow-up, with
      or without medications and without a reoperation for an elevated IOP. Survival
      analysis was used to calculate success rates. RESULTS: The 1- and 2-year success
      rates were 85.4% and 77.9%, respectively. The mean IOP was reduced from 26.3 to
      11.3 mm Hg at 1 year (n=68) and to 11.9 mm Hg at 2 years (n=56), with 60 (88.2%)
      of 68 patients off medication at 1 year and 47 (83.9%) of 56 patients off
      medication at 2 years. Trabeculectomy success rates were significantly lower in
      black compared with nonblack patients (76.2% vs 87.5% at 1 year, P=.03).
      Trabeculectomy failure occurred throughout the follow-up period. Endophthalmitis
      occurred in 2 (2.2%) of the patients, and hypotonia requiring revision occurred
      in 4 (4.5%) of the patients. CONCLUSIONS: Primary trabeculectomy with the use of
      intraoperative mitomycin lowered the IOP by 30% or more in 78% (at 2 years) to
      86% (at 1 year) of the cases and is associated with a marked reduction in the
      percentage of patients who require glaucoma medication. Success rates must be
      evaluated in light of such risks as endophthalmitis and hypotony.

PMID- 9514481
TI  - Association between measures of vitamin A and the ocular fundus findings in
      cerebral malaria.
AB  - OBJECTIVE: To investigate the relationship between serum vitamin A levels and
      conjunctival impression cytology and retinal whitening present in Malawian
      children with cerebral malaria. METHODS: Standard retinal examination and
      conjunctival impression cytology were performed at hospital admission on 101
      consecutively admitted children with cerebral malaria. Blood samples were drawn
      from 56 children at 24 hours, frozen at -20 degrees C, and transported for
      assessment of vitamin A levels by high-performance liquid chromatography.
      Associations among fundus findings and vitamin A measurements were sought.
      RESULTS: The whitening of the retina that we have previously described in
      children with cerebral malaria was found to be associated with a mean+/-SD serum
      vitamin A level of 0.29+/-0.1 micromol/L, compared with a mean vitamin A level of
      0.41+/-0.2 micromol/L in children without retinal whitening. Children with
      retinal whitening were 2.77 (95% CI, 1.06-7.3) times more likely to have abnormal
      conjunctival impression cytology results than those without whitening. No child
      had any clinical or ophthalmologic evidence of chronic vitamin A deficiency.
      CONCLUSIONS: The retinal whitening described in children with cerebral malaria is
      associated with low serum vitamin A levels and with abnormal conjunctival
      impression cytology results and may be due to acute vitamin A deficiency at the
      tissue level.

PMID- 9514482
TI  - United Kingdom Prospective Diabetes Study, 30: diabetic retinopathy at diagnosis
      of non-insulin-dependent diabetes mellitus and associated risk factors.
AB  - OBJECTIVES: To report on the prevalence of retinopathy in patients with newly
      diagnosed non-insulin-dependent diabetes mellitus (NIDDM) and to evaluate the
      relationship of retinopathy to clinical and biochemical variables. DESIGN: A
      multicenter, randomized, controlled clinical study of therapy in patients with
      NIDDM. SETTING AND PATIENTS: Patients were part of the United Kingdom Prospective
      Diabetes Study, a 23-center study of 2964 white patients who had both eyes
      photographed and assessed. OUTCOME MEASURES: The presence and severity of
      diabetic retinopathy were evaluated by sex, and the relationship of retinopathy
      to medical and biochemical parameters was assessed. RESULTS: Retinopathy, defined
      as microaneurysms or worse lesions in at least 1 eye, was present in 39% of men
      and 35% of women. Marked retinopathy with cotton wool spots or intraretinal
      microvascular abnormalities was present in 8% of men and 4% of women. The
      severity of retinopathy was related in both sexes to higher fasting plasma
      glucose levels, higher systolic and diastolic blood pressure, lower serum insulin
      levels, and reduced beta-cell function. In addition, in men, increased alcohol
      consumption was related to increased severity of retinopathy, while leaner women
      had more severe eye lesions. Visual acuity was normal in most patients, but in
      men there was a trend for those with more severe retinal lesions to have worse
      visual acuity. CONCLUSIONS: Diabetic retinopathy is common in patients with newly
      diagnosed NIDDM. Careful ophthalmic assessment at diagnosis is important.

PMID- 9514483
TI  - Three-dimensional ultrasonography of choroidal melanoma: localization of
      radioactive eye plaques.
AB  - OBJECTIVE: To evaluate the use of 3-dimensional (3D) ultrasonography for the
      localization of episcleral eye plaques during the treatment of choroidal
      melanomas. METHODS: A series of 13 patients with choroidal melanoma were treated
      with radioactive palladium 103 seeds affixed into gold eye plaques. During
      surgery, 3D ultrasonography was performed with a commercially available system to
      evaluate the relative position of radioactive plaques secured beneath their
      intraocular tumors. This system consists of an automated, rotating, handheld, B
      scan ultrasonographic probe operating at 10 MHz, a personal computer, and 3D
      imaging software. RESULTS: We measured the margins of the plaque extending beyond
      the tumor and the distance between the radioactive seeds and the tumor apex. We
      also evaluated the relationship between the plaque edge, the episclera, and the
      tumor's edges. While the plaques were well centered over the tumor in all cases,
      the plaque margins around the tumor were found to be variably sized. When
      comparing measurements taken at the time of plaque insertion with those taken at
      the time of plaque removal, we noted changes in the apical tumor height and in
      plaque centration. In the 1 patient with a juxtapapillary tumor, the posterior
      margin of the plaque was found to be displaced away from the sclera, or "tilted."
      CONCLUSIONS: Three-dimensional ultrasonography offers a new method for ophthalmic
      plaque localization. Unique perspectives can be visualized through the use of
      computer-aided 3D reconstructions that permit the assessment of the relative
      position of the plaque to the optic nerve and the measurement of the distance
      between the in vivo radioactive seed and the tumor apex. Our experience suggests
      that when compared with 2-dimensional ultrasonography, 3D ultrasonography offers
      new capabilities that can be used to improve plaque placement and radiation dose
      calculations.

PMID- 9514484
TI  - Neoadjuvant intracarotid chemotherapy for treatment of advanced adenocystic
      carcinoma of the lacrimal gland.
AB  - OBJECTIVE: To investigate a new chemotherapeutic regimen as an adjunct to the
      conventional surgical management of patients with advanced adenocystic carcinoma
      of the lacrimal gland. PATIENTS AND METHODS: Two patients with extensive
      adenocystic carcinoma of the lacrimal gland were treated with intracarotid
      cisplatin and intravenous doxorubicin hydrochloride prior to orbital
      exenteration. Postoperatively, the patients received 55 to 60 Gy of orbital
      irradiation, augmented by additional intravenous cisplatin and doxorubicin.
      Serial clinical and computed tomographic scan examinations were performed to
      monitor for evidence of recurrent disease. RESULTS: Tumor shrinkage was
      documented radiographically following this preoperative chemotherapy regimen,
      downstaging the disease in one case from intracranial involvement to a more
      surgically amenable intraorbital process. Tumor necrosis was confirmed in the
      exenteration specimen. Limited morbidity was experienced and both patients have
      achieved long-term survival to date of 9 1/2 years (114 months) and 7 1/2 years
      (94 months). CONCLUSIONS: To our knowledge, this is the first report of the
      efficacy of neoadjuvant intracarotid chemotherapy in the treatment of an advanced
      adenocystic carcinoma of the lacrimal gland. The combination of cisplatin and
      doxorubicin and the methods of drug delivery may be factors contributory to the
      favorable response. The results of this new treatment regimen are encouraging and
      justify further investigation.

PMID- 9514485
TI  - Selective surgery for intermittent exotropia based on distance/near differences.
AB  - BACKGROUND: Classic teaching suggests that surgery for intermittent exotropia
      should be based on distance/near differences. Divergence excess, according to
      tradition, should be treated with symmetric lateral rectus recessions; simulated
      divergence excess and basic deviations should be treated with a recess/resect
      procedure. This teaching, to our knowledge, has not been systematically tested.
      OBJECTIVES: To evaluate the appropriateness of selective surgery based on
      distance/near differences and to determine if bilateral lateral rectus recessions
      affect the distance deviation more than the near deviation. PATIENTS AND METHODS:
      Patients with basic type intermittent exotropia were randomized to 2 groups,
      those receiving either unilateral recess/resect procedures or symmetric lateral
      rectus recessions. Patients with simulated divergence excess intermittent
      exotropia received symmetric lateral rectus recessions. Outcome was observed 1
      year after surgery. RESULTS: Of 19 patients with basic exotropia receiving
      lateral rectus recessions, 10 patients (52%) had a satisfactory outcome compared
      with 14 (82%) of the 17 patients who had recess/resect procedures (P<.05). Of the
      68 patients with simulated divergence excess, 55 patients (80%) had a
      satisfactory outcome after bilateral/lateral rectus recessions. This result was
      significantly better than the outcome for patients with basic exotropia who
      underwent lateral rectus recessions (P<.05) [corrected]. The decrease in the
      distance/near difference after surgery was essentially identical for patients
      with basic exotropia who underwent lateral rectus recessions as for those who
      received recess/resect procedures (means, 2.4 prism diopters vs 2.1 prism
      diopters, respectively). CONCLUSIONS: Although this study did not evaluate
      increasing the amount of symmetric lateral rectus recessions for patients with
      basic exotropia, these data suggest that patients with basic type intermittent
      exotropia should be treated with recess/resect procedures. Data also suggest that
      patients with simulated divergence excess do well with lateral rectus recessions.
      Recess/resect procedures and symmetric surgery affect distance/near differences
      equally in patients with basic exotropia.

PMID- 9514486
TI  - Strabismus in premature infants in the first year of life. Cryotherapy for
      Retinopathy of Prematurity Cooperative Group.
AB  - OBJECTIVES: To present the 3- and 12-month strabismus data from 3030 premature
      infants with birth weights less than 1251 g enrolled in the Multicenter Trial of
      Cryotherapy for Retinopathy of Prematurity. DESIGN: Data from the 3- and 12-month
      examinations conducted at 23 regional study centers were tabulated for all
      infants. The main outcome measure, ocular motility, was compared with baseline
      demographic variables and retinopathy of prematurity severity for the worse eye.
      Findings at 3 months were compared with the incidence of strabismus at 12 months.
      RESULTS: At 3 months, 200 (6.6%) of the 3030 infants were strabismic. In the 2449
      infants examined at both time points, 289 (11.8%) were found to have strabismus
      at 12 months. Retinopathy of prematurity was significant for strabismus at both 3
      and 12 months (P<.001). The presence of strabismus at 3 months was found to be a
      highly significant predictor of strabismus at 12 months. Anisometropia, abnormal
      fixation, and unfavorable retinal structure also were significant predictors of
      strabismus at 1 year. The total prevalence of strabismus in the first year of
      life was 14.7%. CONCLUSION: The presence of acute-phase retinopathy of
      prematurity places the premature infant at increased risk for strabismus.

PMID- 9514487
TI  - Reattachment rate of human retinal pigment epithelium to layers of human Bruch's
      membrane.
AB  - OBJECTIVES: To determine the reattachment rate of human retinal pigment
      epithelium (RPE) to different layers of human Bruch's membrane (BM). METHODS:
      Explants of BM were prepared from 10 human cadaver eyes by removing native RPE.
      The RPE basal lamina, inner collagenous layer, elastin layer, and outer
      collagenous layer were exposed by sequentially removing each apical layer by
      mechanical or enzymatic means. First-passage human RPE was plated onto the
      surface and the RPE reattachment rate to each layer of BM was determined.
      RESULTS: Retinal pigment epithelial cell reattachment was highest to the inner
      aspects of BM and decreased as deeper layers of BM were exposed (ie, reattachment
      rate to basal lamina was higher than to the inner collagenous layer, which was
      higher than to the elastin layer, which was higher than to the outer collagenous
      layer). The reattachment rate to the inner collagenous layer, elastin layer, and
      outer collagenous layer harvested from elderly donors (age >60 years) was less
      than the reattachment rate to corresponding layers harvested from younger (age
      <50 years) donors. CONCLUSIONS: Retinal pigment epithelial cell reattachment
      depends on the anatomical layer of BM present in the host tissue. Age-related
      changes in BM may interfere with RPE reattachment. Our observations may have
      implications for understanding the pathogenesis of age-related macular
      degeneration and its potential treatment with RPE transplantation techniques.

PMID- 9514488
TI  - In vivo delivery of phosphorothioate oligonucleotides into murine retina.
AB  - OBJECTIVES: To determine the fate of phosphorothioate oligonucleotides (S-ODNs),
      which are commonly used for antisense strategy, in murine retina in vivo with the
      use of fluorescein isothiocyanate (FITC)-labeled S-ODNs, and to evaluate our
      fusogenic liposome system that may facilitate the delivery of S-ODNs. METHODS:
      The FITC-labeled S-ODNs were encapsulated in liposomes, which were then coated
      with the envelope of inactivated hemagglutinating virus of Japan (HVJ; Sendai
      virus) by fusion (HVJ liposomes). Intravitreal injection of naked FITC-labeled S
      ODNs or of the HVJ liposomes was done in ICR mice. After fixation, cryosections
      and flat-mounted retinas were prepared and examined by fluorescence microscopy.
      RESULTS: Injection of naked FITC-labeled S-ODNs at 3 micromol/L exhibited weak
      fluorescence in 13% of the cells in the ganglion cell layer. When the
      concentration was increased to 30 micromol/L, high fluorescence was seen in 59%
      of cells in the ganglion cell layer at this time. This fluorescence diminished
      within a day. In contrast, injection of HVJ liposomes containing FITC-labeled S
      ODNs at 3 micromol/L resulted in high fluorescence in 44% of the cells in the
      ganglion cell layer at 1 hour, and this fluorescence lasted for up to 3 days.
      This treatment also resulted in high fluorescence within retinal vessel walls,
      and weak fluorescence in photoreceptor cells. CONCLUSIONS: Intravitreally
      injected S-ODNs were rapidly eliminated from neural retina, and the use of HVJ
      liposomes could improve the delivery of S-ODNs. This method may be a potentially
      useful system for the antisense-based therapies for retinal diseases.

PMID- 9514489
TI  - Clinical features in affected individuals from 21 pedigrees with dominant optic
      atrophy.
AB  - OBJECTIVE: To assess phenotypic variation of affected individuals from British
      families with autosomal dominant optic atrophy. DESIGN: Eighty-seven patients
      from 21 families showing evidence of linkage to chromosome 3q were identified via
      the Genetic Clinic of Moorfields Eye Hospital, London, England. Genetic linkage
      analysis was carried out with markers from chromosome 3q28-qter. Patients
      underwent clinical examination and psychophysical and electrophysiological
      testing. RESULTS: Best-corrected visual acuity ranged from 20/20 (6/6 m) to light
      perception. Although visual acuity was not significantly worse in older patients
      in the group (chi2=3.20, df=4, P>.50), it did deteriorate with age in one third
      of the families. Subtle or temporal pallor of the optic disc occurred in 96 (55%)
      of 174 eyes and total atrophy in 76 (44%). Tritanopia was found in 6 (7.5%) of 80
      patients; 65 (81.2%) had a mixed color deficit. A cecocentral scotoma was found
      in the vast majority. Peripheral motion detection threshold was elevated in areas
      of visual field with raised mean surround sensitivity but not elsewhere. Pattern
      visual evoked potentials were of reduced amplitude and delayed. Pattern
      electroretinograms showed a reduced N95 component in keeping with primary
      ganglion cell dysfunction. CONCLUSIONS: There is wide intrafamilial and
      interfamilial phenotypic variation in autosomal dominant optic atrophy, with
      visual function in some, but not all, families deteriorating with age. There is
      evidence of degeneration of the ganglion cell layer predominantly from central
      retina, but this is not the exclusive result of either parvocellular or
      magnocellular cell loss.

PMID- 9514490
TI  - Is age-related maculopathy related to hearing loss?
AB  - OBJECTIVE: To describe the relationship of age-related maculopathy (ARM) to
      hearing loss. DESIGN: Population-based cohort study. PARTICIPANTS: All 3397
      adults (age range, 48-92 years) living in Beaver Dam, Wis, who were examined for
      age-related eye disease and hearing loss from March 1, 1993, to July 18, 1995,
      and who had analyzable hearing thresholds in at least 1 ear and fundus
      photographs gradable for ARM in at least 1 eye. METHODS: Characteristics of
      drusen and other lesions typical of ARM were determined by grading stereoscopic
      color fundus photographs using the Wisconsin Age-Related Maculopathy Grading
      System. We used standard protocols of pure-tone air-conduction audiometry to
      assess hearing loss, which was defined as the pure-tone average of hearing
      thresholds at 500, 1000, 2000, and 4000 Hz greater than 25-dB hearing level.
      RESULTS: The prevalence of ARM was 25.4% and of hearing loss was 45.0% in this
      population. Both conditions were present in 15.1%. The relationships between
      early ARM lesions and hearing loss were not statistically significant. After
      controlling for age and sex, persons with late ARM were more likely (odds ratio,
      3.15; 95% confidence interval, 1.34-7.42) to have hearing loss than persons
      without late ARM. This relation did not change when other factors related to ARM
      or hearing loss (eg, cigarette smoking status, history of occupational noise
      exposure, and history of cardiovascular disease) were entered into multivariate
      models. CONCLUSIONS: These population-based estimates document the frequent
      coexistence of signs of ARM and hearing loss. As late ARM is an important cause
      of loss of vision, and as hearing loss is associated with difficulty in
      communicating, the high frequencies of sensory comorbidity may affect maintenance
      of independent functioning as people age. Further study is necessary to examine
      why late ARM and hearing loss are associated.

PMID- 9514492
TI  - Intra-arterial chemotherapy: a welcome new idea for the management of adenocystic
      carcinoma of the lacrimal gland.

PMID- 9514491
TI  - Survival implications of enucleation after definitive radiotherapy for choroidal
      melanoma: an example of regression on time-dependent covariates.
AB  - OBJECTIVE: To evaluate whether the removal of the eye after radiotherapy alters
      the rates of metastatic death in patients with melanoma of the choroid. PATIENTS
      AND METHODS: Using an extension of the Cox model, we based our analysis on a
      cohort of 1541 consecutive patients with unilateral choroidal or ciliary body
      melanoma treated with protons (70 cobalt-gray equivalent in 5 to 7 fractions) at
      the Harvard University (Boston, Mass) cyclotron between July 1, 1975, through
      December 31, 1993, and who were observed prospectively up to September 30, 1995.
      Patient survival and the status of the treated eye were updated annually.
      RESULTS: By September 1995 (median follow-up among survivors, 8 years), 137
      patients underwent enucleation after radiotherapy for complications (n=103) or
      tumor regrowth (n=34). The overall 10-year rate of eye retention was 89% (95%
      confidence interval, 87%-91%). Of the 1541 patients, 300 died of tumor
      metastasis, 38 following enucleation of the affected eye (mean interval from
      enucleation to death, 25 months). The multivariate rate ratio for metastatic
      death associated with enucleation (modeled as a time-dependent covariate) was 0.9
      (95% confidence interval, 0.6-1.4) for enucleation due to complications and 3.8
      (95% confidence interval, 2.3-6.3) for enucleation associated with tumor
      regrowth. CONCLUSIONS: In the absence of tumor viability, enucleation after
      primary irradiation for choroidal melanoma has no deleterious effect on patients'
      survival. Enucleation concurrent with tumor regrowth is associated with high
      death rates; growth of the tumor in the eye may presage systemic recurrence and
      death from metastasis.

PMID- 9514493
TI  - An uncommon malignant neoplasm of the caruncle: report of a case of
      undifferentiated carcinoma.
AB  - The caruncle is an uncommon site for the occurrence of neoplasm despite its
      diverse histological composition of conjunctival, lacrimal, and skin tissues. The
      following case report describes a 66-year-old man who suffered from a primary
      undifferentiated carcinoma of the left caruncle. He remained well with no
      evidence of recurrence 24 months after a complete surgical excision. To our
      knowledge, this could represent the first case of undifferentiated carcinoma of
      the caruncle to be reported in the English literature. Early detection and
      complete excision for this type of lesion could lead to a satisfactory clinical
      outcome.

PMID- 9514495
TI  - Intraocular anesthetic following peribulbar anesthesia.

PMID- 9514494
TI  - Juvenile xanthogranuloma of the iris in an adult.
AB  - Juvenile xanthogranuloma is a self-limited skin disorder of young children that
      uncommonly affects the eye. Juvenile xanthogranuloma has been described in
      adults, but reported intraocular involvement is extremely rare. We report a case
      of juvenile xanthogranuloma diagnosed in a 25-year-old man who was seen with
      nontraumatic hyphema and iridocyclitis. Diagnosis was made from a biopsy specimen
      obtained from a suspicious skin lesion. Topical and systemic steroids, radiation
      therapy, and finally immunosupression were required to eliminate the iris tumor
      clinically and resolve the patient's recurrent symptoms.

PMID- 9514497
TI  - Idiopathic polypoidal choroidal vasculopathy: a peripheral lesion.

PMID- 9514496
TI  - Study of the Norrie disease gene in 2 patients with bilateral persistent
      hyperplastic primary vitreous.

PMID- 9514498
TI  - Brainstem hypoplasia in the Wildervanck (cervico-oculo-acoustic) syndrome.

PMID- 9514500
TI  - Vitamin A deficiency and xerophthalmia in an autistic child.

PMID- 9514499
TI  - Ritleng intubation system for treatment of congenital nasolacrimal duct
      obstruction.
AB  - Twenty-eight patients (34 eyes) with congenital nasolacrimal duct obstruction
      underwent silicone intubation with the Ritleng lacrimal intubation system. The
      technique involves introduction of a Prolene (Ethicon Inc, Somerville, NJ)
      monofilament guide thread, securely fastened to the silicone tubing, into a
      tubular metal probe that opens into the inferior meatus. The outcome was
      evaluated in terms of ease of intubation and objective success rate. Thirty-two
      (94%) of the 34 lacrimal systems were successfully intubated with the Ritleng
      system. Difficulty passing the Prolene thread through the probe and out the tip,
      necessitating conversion to a Crawford intubation system, was encountered in only
      2 eyes (6%). The Prolene spontaneously emerged from the nose in 24 (75%) of 32
      eyes, making retrieval simple and uncomplicated. The success rate for relieving
      signs and symptoms of obstruction was 97% (31/32) for the eyes with the Ritleng
      system and 100% (2/2) for the eyes with the Crawford system. Bicanalicular
      silicone intubation with the Ritleng intubation system is an easy and effective
      technique for treatment of congenital nasolacrimal duct obstruction.

PMID- 9514501
TI  - Avulsion of the optic nerve head after orbital trauma.

PMID- 9514502
TI  - Topical aminocaproic acid in the treatment of patients with traumatic hyphema.

PMID- 9514504
TI  - Latanoprost and physostigmine in human eyes.

PMID- 9514503
TI  - Selectivity in glaucoma injury.

PMID- 9514505
TI  - A response to uveal melanoma: growth rate and prognosis.

PMID- 9514506
TI  - Hydrocephalus in Maroteaux-Lamy syndrome.

PMID- 9514507
TI  - Premotor neurons for vertical eye movements in the rostral mesencephalon of
      monkey and human: histologic identification by parvalbumin immunostaining.
AB  - In the monkey, premotor neurons for vertical gaze are located in the
      mesencephalic reticular formation: the rostral interstitial nucleus of the medial
      longitudinal fascicle (riMLF) contains medium-lead burst neurons, and the
      interstitial nucleus of Cajal (iC) acts as integrator for the eye-velocity
      signals to eye-position signals. Both nuclei lie adjacent to each other and are
      similar in appearance at the transition zone in Nissl-stained sections, which
      makes a delineation of the functionally different nuclei difficult in human. For
      a neuropathologic analysis of degenerative changes in saccadic disorders of
      patients, the histologic identification of the riMLF and the iC is important. The
      aim of this study is to identify both nuclei in human by using parvalbumin as a
      histologic marker. First, in monkeys the premotor neurons in riMLF and iC were
      identified by trans-synaptic labelling after injections of tetanus toxin fragment
      C into vertical-pulling eye muscles. Premotor neurons were found in the riMLF
      mainly ipsilateral to the corresponding eye muscle motoneurons and on both sides
      within the iC, but here the labelled cell populations differed: the contralateral
      side contained more medium-sized cells compared with the mainly small-sized cell
      population on the ipsilateral side. Double labelling showed that almost all
      premotor neurons in the iC and all premotor neurons in the riMLF were parvalbumin
      immunoreactive. The immunocytochemical staining of human brainstem sections
      revealed the riMLF as a cluster of medium-sized, elongated parvalbumin-positive
      cells, with a similar appearance and at a similar location as that in monkey: a
      wing-shaped nucleus dorsomedial to the red nucleus, rostral to the traversing
      tractus retroflexus, dorsally bordered by the thalamo-subthalamic paramedian
      artery. The adjacent iC could be distinguished easily by its more densely packed,
      round parvalbumin-immunoreactive neurons. The exact identification of premotor
      neurons of the vertical system in the normal human brain provides a reference
      basis for the neuropathologic analysis of vertical gaze disorders at a cellular
      level.

PMID- 9514508
TI  - Twofold overexpression of human beta-amyloid precursor proteins in transgenic
      mice does not affect the neuromotor, cognitive, or neurodegenerative sequelae
      following experimental brain injury.
AB  - By using transgenic mice that overexpress human beta-amyloid precursor proteins
      (APPs) at levels twofold higher than endogenous APPs, following introduction of
      the human APP gene in a yeast artificial chromosome (YAC), we examined the
      effects of controlled cortical impact (CCI) brain injury on neuromotor/cognitive
      dysfunction and the development of Alzheimer's disease (AD)-like neuropathology.
      Neuropathological analyses included Nissl-staining and immunohistochemistry to
      detect APPs, beta-amyloid (Abeta), neurofilament proteins, and glial fibrillary
      acidic protein, whereas Abeta levels were measured in brain homogenates from mice
      subjected to CCI and control mice by using a sensitive sandwich enzyme-linked
      immunosorbent assay. Twenty APP-YAC transgenic mice and 17 wild type (WT)
      littermate controls were anesthetized and subjected to CCI (velocity, 5 m/second;
      deformation depth, 1 mm). Sham (anesthetized but uninjured) controls (n = 10 APP
      YAC; n = 8 WT) also were studied. Motor function was evaluated by using rotarod,
      inclined-plane, and forelimb/hindlimb flexion tests. The Morris water maze was
      used to assess memory. Although CCI induced significant motor dysfunction and
      cognitive deficits, no differences were observed between brain-injured APP-YAC
      mice and WT mice at 24 hours and 1 week postinjury. By 1 week postinjury, both
      cortical and hippocampal CA3 neuron loss as well as extensive astrogliosis were
      observed in all injured animals, suggesting that overexpression of human APPs
      exhibited no neuroprotective effects. Although AD-like pathology (including
      amyloid plaques) was not observed in either sham or brain-inj ured animals, a
      significant decrease in brain concentrations of only Abeta terminating at amino
      acid 40 (Abeta x-40) was observed following brain injury in APP-YAC mice (P <
      0.05 compared with sham control levels). Our data show that the APP-YAC mice do
      not develop AD-like neuropathology following traumatic brain injury. This may be
      because this injury does not induce elevated levels of the more amyloidogenic
      forms of human Abeta (i.e., Abeta x-42/43) in these mice.

PMID- 9514509
TI  - Cortical projections of the parvocellular laminae C of the dorsal lateral
      geniculate nucleus in the cat: an anterograde wheat germ agglutinin conjugated to
      horseradish peroxidase study.
AB  - The areal and laminar distributions of the projection from the parvocellular part
      of laminae C of the dorsal lateral geniculate nucleus (Cparv) were studied in
      visual cortical areas of the cat with the anterograde tracing method by using
      wheat germ agglutinin conjugated to horseradish peroxidase. A particular
      objective of this study was to examine the central visual pathways of the W-cell
      system, the precise organization of which is still unknown. Because the Cparv in
      the cat is said to receive W-cell information exclusively from the retina and the
      superior colliculus, the results obtained would provide an anatomical substrate
      for the W-cell system organization in mammals. The results show that the cortical
      targets of the Cparv are areas 17, 18, 19, 20a, and 21a and the posteromedial
      lateral suprasylvian (PMLS) and ventral lateral suprasylvian(VLS) areas. In area
      17, the projection fibers terminate in the superficial half of layer I; the lower
      two-thirds of layer III, extending to the superficial part of layer IV; and the
      deep part of layer IV, involving layer Va. These terminations form triple bands
      in area 17. The projection terminals in layer I are continuous, whereas those in
      layers III, IV, and Va distribute periodically, exhibiting a patchy appearance.
      In areas 18 and 19, the projection fibers terminate in the superficial half of
      layer I and in the full portions of layers III and IV, forming double bands. In
      these areas, the terminals in layer I are continuous, whereas those in layers III
      and IV distribute periodically, exhibiting a patchy appearance. In area 20a, area
      21a, PMLS, and VLS, projection fibers terminate in the superficial part of layer
      I, in part of layer III, and in the full portion of layer IV, although they are
      far fewer in number than those seen in areas 17, 18, and 19. The present results
      demonstrate that the Cparv fibers terminate in a localized fashion in both the
      striate and the extrastriate cortical areas and that these W-cell projections are
      quite unique in their areal and laminar organization compared with the X- and Y
      cell systems.

PMID- 9514510
TI  - Retinal ganglion cells expressing the FOS protein after light stimulation in the
      Syrian hamster are relatively insensitive to neonatal treatment with monosodium
      glutamate.
AB  - In nocturnal rodents, the c-fos gene is directly involved in the light mechanism
      of resetting of the suprachiasmatic nucleus (circadian clock). Light also induces
      c-fos expression in the retinal ganglion cell layer (GCL), but no attempt has
      been made to study the retinal responses to the phase-shifting effects of light.
      The expression of the Fos protein in each of the two populations of the GCL
      (displaced amacrine cells [DACs] and ganglion cells [GCs]) was analyzed in
      hamsters after light stimulation delivered early (circadian time [CT13]) and in
      the middle (CT18) of the subjective night. To evaluate as accurately as possible
      the number of GCs able to phase shift the locomotor activity rhythm (LAR),
      neonatal hamsters treated with monosodium glutamate (MSG) were also used, an in
      vivo model which displays retinal degeneration and LAR normally entrained by
      light. In nontreated hamsters, the number of Fos-immunoreactive (Fos-ir+) nuclei
      in the GCL was significantly higher at CT18 than at CT13. In MSG-treated
      hamsters, the number of Fos-ir+ nuclei was the same at both CTs and
      nonsignificantly different as those of nontreated hamsters at CT13. MSG treatment
      destroyed as many Fos-ir+ DACs as Fos-ir- DACs or Fos-ir+ GCs. Fos-ir+ GCs were
      less sensitive to neurotoxic than other GCs, as only 37% of them were destroyed
      by treatment versus 92% for Fos-ir- GCs. At CT18, a maximum of 3,500 GCs
      expressed Fos protein in nontreated hamsters versus only 2,200 in MSG-treated
      hamsters. This minor subgroup was sufficiently potent to normally synchronize the
      circadian rhythms to the Light/dark cycle in treated hamsters.

PMID- 9514511
TI  - Organizing principles of cortical integration in the rat neostriatum:
      corticostriate map of the body surface is an ordered lattice of curved laminae
      and radial points.
AB  - The neuroanatomic organizing principles underlying integrative functions in the
      striatum are only partially understood. Within the three major subdivisions of
      the striatum-sensorimotor, associative, and limbic--longitudinal zones of axonal
      plexuses from the cerebral cortex end in bands and clusters that innervate cell
      groups. To identify organizing principles of the corticostriate bands and
      clusters, we localized somatosensory cortical cells receptive to light touch on
      the hindlimb, forelimb, or vibrissae by extracellular recording, and we labeled
      their projections by iontophoretic application of dextran anterograde tracers.
      The results show that cortical cells in columnar groups project to the striatum
      in the form of successive strips, or laminae, that parallel the curve of the
      external capsule. The vibrissae somatosensory cortex projects to the most lateral
      lamina. Just medial to the vibrissae projection, the major axonal arborizations
      arising from hindlimb and forelimb somatosensory cortex are organized within a
      common lamina, where they interdigitate and overlap as well as remain separate.
      In addition, the hindlimb and forelimb cortex send small projections to the
      vibrissae lamina, and vice versa, forming broken, radially oriented lines of
      points across the laminar strips. The major somatosensory projections are in the
      dorsolateral, calbindin-poor sensorimotor striatum, whereas the radially oriented
      projection points extend into the medial, calbindin-rich associative striatum.
      Extending previous studies of corticostriate projections, this report shows a
      grid translation of columnar somatosensory cortical inputs into striatum and a
      detailed map for the rat sensorimotor zone. The lattice-like grid is a novel
      functional/neuroanatomic organization that is ideal for distributing, combining,
      and integrating information for sensorimotor and cognitive processing.

PMID- 9514512
TI  - Effects of postnatal anti-NGF on the development of CGRP-IR neurons in the dorsal
      root ganglion.
AB  - Experiments were undertaken to examine anatomical correlates of physiological
      effects of rabbit sera raised against nerve growth factor (anti-NGF) on
      nociceptive afferents. This antiserum has been shown to deplete the population of
      A-delta high threshold mechanoreceptors and to reduce neurogenic vasodilatation.
      Because numerous studies implicate calcitonin gene related peptide (CGRP)
      containing sensory neurons in these effects, immunocytochemical and anatomical
      techniques were used to examine the normal development of CGRP-immunoreactive (
      IR) neurons in the dorsal root ganglion (DRG) of rats from 13 days to 19 weeks of
      age, and to compare this to the development in rats treated neonatally (postnatal
      days 2-14) with anti-NGF. In controls the rate of increase in the mean diameter
      of CGRP-IR cells was substantially greater between 13 days and 5 weeks of age
      than it was between 5 weeks and 19 weeks, in contrast to CGRP-negative neurons
      whose rate of growth remained relatively constant. Anti-NGF had no significant
      effect on growth rate, but rats treated with anti-NGF exhibited a reduced
      proportion of CGRP-IR neurons at 5 weeks. This deficit was reversed by 19 weeks
      unlike the physiological changes. These results indicate independent regulation
      of CGRP expression and nociceptor physiology by NGF.

PMID- 9514513
TI  - Dependence of parvalbumin expression on Purkinje cell input in the deep
      cerebellar nuclei.
AB  - A complete loss of Purkinje cell (PC) input leads to an increase in expression of
      the calcium-binding protein parvalbumin (Parv) in neurons of the deep cerebellar
      nuclei (DCN) of PC degeneration (pcd) mutants. To verify this apparent dependence
      of Parv expression on PC input in the DCN, the patterns of expression in five
      other cerebellar mutants (weaver, staggerer, leaner, nervous, and lurcher) with
      differing grades and chronologies of PC loss were compared. Degree and time
      course of PC loss and the subsequent denervation of DCN neurons were monitored by
      using Calbindin D-28k (Calb) immunocytochemistry. Similar to pcd mice, somatal
      Parv in lurcher mutants increased massively throughout the cerebellar nuclei. In
      nervous and leaner mutants, somatal Parv was restricted to almost completely
      denervated nuclear areas, whereas areas with appreciable remnants of PC input
      were spared. The first appearance of Parv+ somata was closely correlated with the
      time course of PC degeneration--postnatal day 19 in lurcher mutants and postnatal
      day 23 in nervous mutants. In staggerer mice, neurons immunopositive for Parv as
      well as for Calb were present in outer DCN areas, likely representing ectopic PCs
      rather than DCN neurons. No Parv+ DCN somata were found in weaver mutants at any
      time. In conclusion, increased expression of somatal Parv in DCN neurons is not
      restricted to the specific histopathology in pcd mutants but is a common
      mechanism that is dependent on the topography and severeness of PC-input loss.
      The functional significance of the Parv increase and its possible contribution to
      the degree of motor disability among the different mutants are discussed.

PMID- 9514514
TI  - Brain protein phosphatase 2A: developmental regulation and distinct cellular and
      subcellular localization by B subunits.
AB  - Protein phosphatase 2A (PP2A) is a heterotrimeric enzyme consisting of a
      catalytic subunit (C), a structural subunit (A), and a variable regulatory
      subunit (B). We have investigated the spatial and temporal expression patterns of
      three members of the B subunit family, Balpha, Bbeta, and Bgamma, both at the
      message level by using ribonuclease protection analysis and at the protein level
      by using specific antibodies. Although A, Balpha, and C protein are expressed in
      many tissues, Bbeta and Bgamma were detectable only in brain. Balpha, Bbeta, and
      Bgamma are components of the brain PP2A heterotrimer, because they copurified
      with A and C subunits on immobilized microcystin. Whereas Balpha and Bbeta are
      mainly cytosolic, Bgamma is enriched in the cytoskeletal fraction. In contrast to
      A, C, and Balpha, which are expressed at constant levels, Bbeta and Bgamma RNA
      and protein are developmentally regulated, with Bbeta levels decreasing and
      Bgamma levels increasing sharply after birth. RNA and immunoblot analyses of
      subdissected brain regions as well as immunohistochemistry demonstrated that B
      subunits are expressed in distinct but overlapping neuronal populations and
      cellular domains. These data indicate that B subunits confer tissue and cell
      specificity, subcellular localization, and developmental regulation to the PP2A
      holoenzyme. The Balpha-containing heterotrimer may be important in general
      neuronal functions that involve its partially nuclear localization. Holoenzymes
      containing B likely function in early brain development as well as in somata and
      processes of subsets of mature neurons. Bgamma may target PP2A to cytoskeletal
      substrates that are important in the establishment and maintenance of neuronal
      connections.

PMID- 9514515
TI  - Relationship of mu- and delta-opioid receptors to GABAergic neurons in the
      central nervous system, including antinociceptive brainstem circuits.
AB  - Inhibition of neurons containing gamma-aminobutyric acid (GABA) may underlie some
      of the excitatory effects of opioids in the central nervous system (CNS). In the
      present study, we examined the relationship of the cloned mu- and delta-opioid
      receptors (MOR1 and DOR1, respectively) to GABAergic neurons in brain and spinal
      cord. This was done by combining immunofluorescent staining for MOR1 or DOR1 with
      that for GABA or glutamic acid decarboxylase (GAD); fluorescent retrograde tract
      tracing was used in some cases to identify neurons with particular projections.
      In rats, cells double labeled for GABA and MOR1 were observed in layers II-VI of
      the parietal cortex and in layers II-IV of the piriform cortex. In the
      hippocampus, double labeling was observed in the dentate gyrus and in regions CA1
      and CA3. Double labeling was very prominent in the striatum and in the reticular
      nucleus of the thalamus; it was also observed in other portions of the
      diencephalon. However, double labeling for GABA and MOR1 was never observed in
      the cerebellar cortex. Cells double labeled for GABA and MOR1 were common in the
      periaqueductal gray (PAG) and the medial rostral ventral medulla (RVM) of both
      rats and monkeys, suggesting that involvement of GABAergic neurons with
      supraspinal opioid antinociception may extend to primates. In the RVM of rats,
      many of those double-labeled neurons were retrogradely labeled from the dorsal
      spinal cord. In contrast, double-labeled neurons in the PAG were almost never
      retrogradely labeled from the RVM. No unequivocal examples of double labeling for
      DOR1 and GAD were found in any region of the CNS that we examined in either rats
      or monkeys. However, GABAergic neurons were often apposed by DOR1 immunoreactive
      varicosities. Our findings suggest that activation of mu-opioid receptors
      directly modulates the activity of GABAergic neurons throughout the CNS,
      including neurons involved in the supraspinal component of opioid analgesia. In
      contrast, delta-opioid receptors appear to be positioned to modulate the activity
      of GABAergic neurons indirectly.

PMID- 9514516
TI  - International Microsurgical Society Thirteenth Congress: some historical
      highlights.

PMID- 9514517
TI  - The value of continuous electrical muscle stimulation using a completely
      implantable system in the preservation of muscle function following motor nerve
      injury and repair: an experimental study.
AB  - Functional recovery following motor nerve injury and repair is directly related
      to the degree of muscle atrophy that takes place during the period of nerve
      regeneration. The extent of this muscle atrophy is related to a number of factors
      including the accuracy of nerve repair; the distance through which the nerve must
      regenerate; the age of the patient; and the type of nerve injury and other
      associated tendon and soft tissue and bony damage. Atrophy of muscle that is
      always associated with nerve injury is a combination of disuse and degeneration.
      Our hypothesis proposed the following question: "Would continuous electrical
      stimulation of the denervated muscle during the period of nerve regeneration
      maintain the integrity of the muscle fibers and hence their potential functional
      capacity?" We have completed a series of animal studies (rabbit and canine
      models) in our laboratory using a completely implantable system to provide
      continuous muscle stimulation following nerve injury and microsurgical repair. In
      several different experiments, the nerves under study were cut and repaired at 4
      and 12 cm from the muscles to study the effects of short- and long-term recovery.
      In all experiments, a beneficial effect was demonstrated with improved morphology
      and functional capacity of the reinnervated stimulated muscles when compared with
      nonstimulated controls. In addition, electrical stimulation using this
      implantable system could be applied for extended periods without evidence of
      discomfort in the experimental animals.

PMID- 9514518
TI  - A clinical pilot study to assess functional return following continuous muscle
      stimulation after nerve injury and repair in the upper extremity using a
      completely implantable electrical system.
AB  - This clinical pilot study evolved from a 10-year experience in the experimental
      laboratory using continuous muscle stimulation in a series of animal studies
      following nerve injury and microsurgical repair. A completely implantable system
      was developed (Medtronic) to provide electrical stimulation to the denervated
      muscles until nerve regeneration had occurred. Both peripheral nerve injuries in
      the extremities and facial nerve severances were studied, and a definite
      improvement in functional capacity was obtained as well as improved morphology
      compared with nonstimulated controls. In this study, 13 patients with peripheral
      nerve injuries in the upper extremity are included. All patients had muscle
      stimulation for extended periods until nerve regeneration was evident; a careful
      analysis of their functional capacity was then completed. There were five
      patients with median nerve injuries, four with ulnar nerve or combined median
      ulnar nerve injuries, and four with severed radial nerves. All patients showed
      satisfactory nerve regeneration on clinical examination and electromyographic
      studies. Motor recovery was usually better than sensory return. Functional muscle
      analysis varied somewhat from patient to patient, but every patient had a
      satisfactory to excellent recovery. Patients with low nerve lesions had better
      results, but muscle recovery even in patients with mid-forearm or higher nerve
      injuries was most encouraging. Functional recovery in radial nerve injuries was
      close to normal in all cases. The results from this pilot study have clearly
      shown the benefits of continuous muscle stimulation using an implantable system
      following nerve injury and repair.

PMID- 9514519
TI  - Fibroblast growth factor pretreatment of 1-mm PTFE grafts.
AB  - When using microvascular polytetrafluoroethylene (PTFE) vascular grafts, the best
      results in terms of patency rate and neoendothelialization are obtained with
      prostheses with thin walls and long fibril length (i.e., 90 microm). A complete
      internal neoendothelial lining is usually achieved at 12 weeks after
      implantation. Clinically, this period can be too long. In this study, 1-mm
      internal diameter PTFE prostheses with optimal physical characteristics were
      pretreated with basic fibroblast growth factor in fibrin glue, a potent
      endothelial cell mitogen, and chemoattractant. Rate, speed, extent, quality, and
      origin of neoendothelium were compared with two control groups, using Evans Blue
      dye, immunohistochemical localization of factor VIII von Willebrand factor
      protein, and scanning electron microscopy. Prostheses (8 mm long) were implanted
      in the infrarenal rat aorta and harvested after 3 weeks. In treated grafts, the
      amount of endothelial regeneration was greater than in untreated grafts (75% of
      the internal surface compared with 30%). However, patency rate in the
      experimental group was lower than in the control groups. This study provides new
      data on neoendothelial regeneration in small-diameter PTFE grafts.

PMID- 9514520
TI  - Cell proliferation in a peripheral target is required for the induction of
      central neurogenesis in the leech.
AB  - Several days after the completion of the early phase of cell proliferation that
      generates most of the leech central nervous system, the pair of "sex ganglia" in
      the two reproductive segments of the midbody undergo a second period of
      neurogenesis that gives rise to several hundred peripherally induced central
      (PIC) neurons. This proliferative phase, which begins on embryonic day 17 (E17),
      is induced by the interaction of a few specific neurons in the sex ganglia with a
      peripheral target, the male genitalia, during a critical period that extends from
      E13 to E16. The central nervous system (CNS) determines the critical period,
      since the male genitalia have the capacity to induce PIC neurons beginning on E10
      and continuing throughout embryogenesis. Here we first show, by injecting
      hydroxyurea into staged embryos to ablate dividing cells, that PIC neuron
      precursors begin to divide at a low rate before E17, during the critical period.
      Then, through a series of homochronic and heterochronic male organ
      transplantations combined with hydroxyurea treatment of hosts and/or donors, we
      show that cell proliferation is required in the target itself for it to be
      competent to induce PIC neurons. These observations demonstrate that a nerve
      connection can couple cell proliferation in a peripheral target to cell
      proliferation in the CNS, providing a novel means for size adjustment of a
      central neuronal population relative to a peripheral target.

PMID- 9514521
TI  - Islet injury induces neurotrophin expression in pancreatic cells and reactive
      gliosis of peri-islet Schwann cells.
AB  - Pancreatic islets are enveloped by a sheath of Schwann cells, the glial cells of
      the peripheral nervous system (PNS). The fact that Schwann cells of the PNS
      become reactive and express nerve growth factor (NGF) and other growth factors
      following axotomy suggested the possibility that peri-islet Schwann cells could
      become activated by islet injury. To test this hypothesis, we examined two animal
      models of islet injury. The first model was mice and rats injected with
      streptozotocin (SZ), a specific beta-cell toxin. The second model was NOD mice, a
      strain in which beta cells are deleted by an autoimmune process. We found that
      peri-islet Schwann cells became reactive following islet injury and began to
      express increased levels of NGF and the neurotrophin receptor p75. Lesions to the
      pancreas also markedly induced NGF expression by exocrine and endocrine cells.
      Neurotrophin expression was not unique to adult tissues since pancreatic cells
      transiently expressed p75, the NGF receptor Trk A, and NGF during development.
      These observations suggest that NGF could play an important role in pancreas
      during embryogenesis and in processes leading to repair following islet injury in
      adults.

PMID- 9514522
TI  - Identification and characterization of tenp, a gene transiently expressed before
      overt cell differentiation during neurogenesis.
AB  - The initiation of cellular differentiation in the vertebrate central nervous
      system is a cascade of regulated gene expression events involving both intrinsic
      and extrinsic factors. Currently, the molecular events underlying the
      developmental transition from the cessation of cell proliferation to the onset of
      cell differentiation during neurogenesis are still poorly understood. We have
      identified a gene, tenp, which is likely to play a role during the transition.
      tenp mRNA was detected in the developing retina and brain, but not in the heart,
      kidney, or liver. Anatomically, cells expressing tenp formed a narrow strip at
      the boundary between the ventricular zone (consisting of proliferating cells) and
      the intermediate zone (occupied by postmitotic, differentiating cells). Further
      analysis showed that they were bromodeoxyuridine negative and thus postmitotic,
      yet without apparent differentiation such as the expression of microtubule
      associated protein (MAP2) and neurofilament (NF68). When expressed in chicken
      embryonic fibroblast cells through transfection, Tenp protein was immunodetected
      in membrane fractions, implying that Tenp might be a membrane protein as
      predicted by a computer analysis of its primary sequence. Our data suggested that
      tenp might be involved in an early neurogenic event that existed transiently
      after terminal mitosis, yet before the overt differentiation of neural precursor
      cells.

PMID- 9514523
TI  - Changes in catecholamine levels and turnover rates in hypothalamic, vocal
      control, and auditory nuclei in male zebra finches during development.
AB  - The catecholamines norepinephrine (NE) and dopamine (DA) have been implicated in
      the sexual differentiation of brain and behavior and in species-specific learning
      in several species. To determine if these neurotransmitters might be involved in
      sexual differentiation of the vocal control system and song learning in male
      zebra finches, NE and DA levels and turnover rates were quantified in 10
      behaviorally relevant brain nuclei [6 vocal control (VCN), 2 auditory (AN), and 2
      hypothalamic (HN)] at four critical points during sexual differentiation of the
      VCN and the period of song learning, 25, 35, 55, and 90 days of age. Some birds
      were pretreated with alpha-methyl-para-tyrosine (alphaMPT) to allow estimation of
      NE and DA turnover rates. NE and DA levels in microdissected nuclei were
      quantified using high-performance liquid chromatography with electrochemical
      detection. AlphaMPT treatment suppressed catecholamine synthesis just as
      effectively in juveniles as it does in adults and proved an effective method for
      estimating NE and DA turnover rates. Patterns of NE and DA function in most VCN
      and AN over development were quite different from those in HN in which NE and DA
      function changed gradually and showed no striking peaks. NE turnover rates
      changed significantly over development in all six VCN [nucleus interfacialis
      (Nlf), high vocal center (HVC), nucleus robustus of the archistriatum (RA),
      dorsomedial portion of the intercollicular nucleus (DM), Area X of the
      parolfactory lobe, and lateral portion of the magnocellular nucleus of the
      anterior neostriatum (IMAN)]; one AN [nucleus mesencephalicus lateralis pars
      dorsalis (MLd)], and one HN [preopticus anterior (POA)]. NE levels changed
      significantly in two VCN (Nlf and Area X). In Nlf, RA, Area X, IMAN, and MLd, NE
      levels and/or turnover rates showed a striking peak at day 25, which was not seen
      in HN. Both DA levels and turnover rates changed profoundly over development in 5
      of 6 VCN (Nlf, RA, DM, Area X, and IMAN) and both AN (MLd and Field L). These
      nuclei showed striking peaks in DA levels and turnover rates, primarily on day 35
      and/or 55, which then declined profoundly by day 90. This contrasted with the
      minimal change in DA turnover rates seen in one HN (POA) and the sixth VCN, HVC.
      In several VCN and AN, NE and DA levels and turnover rates during development
      reached levels never seen in adult males. Previous research has shown that
      catecholamine function is heightened in VCN during development compared to
      surrounding tissues. Our data demonstrate that NE and DA function during
      development shows pronounced peaks in most VCN not seen in HN. This is
      interesting because both VCN and HN are hormone sensitive, and both show hormone
      modulated NE and DA function in adult males. The timing of these peaks suggests
      that increased catecholaminergic function may be involved in sexual
      differentiation of the VCN and song learning in finches.

PMID- 9514524
TI  - Sympathetic axons surround nerve growth factor-immunoreactive trigeminal neurons:
      observations in mice overexpressing nerve growth factor.
AB  - It has been postulated that the aberrant projection of sympathetic axons to
      individual primary sensory neurons may provide the morphological basis for pain
      related behaviors in rat models of chronic pain syndrome. Since nerve growth
      factor (NGF) can elicit the collateral sprouting of noradrenergic sympathetic
      terminals, it might be predicted that NGF plays a role in mediating the sprouting
      of sympathetic axons into sensory ganglia. Using a line of transgenic mice
      overexpressing NGF among glial cells, it was first found that trigeminal ganglia
      from adult transgenic mice possessed significantly higher levels of NGF protein
      in comparison to age-matched wild-type mice; as well, detectable levels of NGF
      mRNA transgene expression were present in both the ganglia and brain stem. Within
      the trigeminal ganglia, a small proportion of the sensory neuronal population
      stained immunohistochemically for NGF; a higher percentage of NGF-positive
      neurons was evident in transgenic mice. New sympathetic axons extended into the
      trigeminal ganglia of transgenic mice only and formed perineuronal plexuses
      surrounding only those neurons immunostained for NGF. In addition, such plexuses
      were accompanied by glial processes from nonmyelinating Schwann cells. From these
      data, we propose that accumulation of glial-derived NGF by adult sensory neurons
      and its putative release into the ganglionic environment induce the directional
      growth of sympathetic axons to the source of NGF, namely, the cell bodies of
      primary sensory neurons.

PMID- 9514525
TI  - Early development of an identified serotonergic neuron in Helisoma trivolvis
      embryos: serotonin expression, de-expression, and uptake.
AB  - In early-stage embryos of Helisoma trivolvis, a bilateral pair of identified
      neurons (ENC1) express serotonin and project primary descending neurites that
      ramify in the pedal region of the embryo prior to the formation of central
      ganglia. Pharmacological studies suggest that serotonin released from ENC1 acts
      in an autoregulatory pathway to regulate its own neurite branching and in a
      paracrine or synaptic pathway to regulate the activity of pedal ciliary cells. In
      the present study, several key features of early ENC1 development were
      characterized as a necessary foundation for further experimental studies on the
      mechanisms underlying ENC1 development and its physiological role during
      embryogenesis. ENC1 morphology was determined by confocal microscopy of serotonin
      immunostained embryos and by differential-interference contrast (DIC) microscopy
      of live embryos. The soma was located at an anteriolateral superficial position
      and contained several distinguishing features, including a large spherical
      nucleus with prominent central nucleolus, large granules in the apical cytoplasm,
      a broad apical dendrite ending in a sensory-like structure at the embryonic
      surface, and a ventral neurite. ENC1 first expressed serotonin immunoreactivity
      around stage E13, followed immediately by the appearance of an immunoreactive
      neurite (stage E14). Both the intensity of immunoreactivity and primary neurite
      length were consistently greater in the right ENC1 at early stages. Serotonin
      uptake, as indicated by 5,7-dihydroxytryptamine-induced fluorescence, first
      occurred between stages E18 and E25. At later stages of embryogenesis (after
      stage E65), serotonin immunoreactivity disappeared, whereas serotonin uptake and
      normal cell morphology were retained.

PMID- 9514526
TI  - An enhanced olfactory marker protein immunoreactivity in individual olfactory
      receptor neurons following olfactory bulbectomy may be related to increased
      neurogenesis.
AB  - Olfactory marker protein (OMP) is a 19-kD acidic protein found throughout the
      cytoplasm of mature olfactory receptor neurons (ORNs). Its function remains
      unknown. Following olfactory bulbectomy, the proportion of ORNs mature enough to
      express OMP declines greatly. However, in the few remaining mature ORNs, it has
      been observed that the intensity of OMP immunoreactivity (IR) appears to increase
      over that of ORNs on the unoperated side. We have now investigated this
      phenomenon quantitatively in rats subjected to unilateral olfactory bulbectomy.
      Results show that at all postbulbectomy survival periods examined quantitatively
      (3 days to 6 months), a significant decrease (19-37%) occurs in the transmission
      of incident light through OMP(+)-ORNs in bulbectomized versus unoperated
      olfactory epithelium (OE). Further, we also observed a consistent side-to-side
      difference in OMP IR in control unoperated animals. Possible explanations for
      these observations and their relation to the still unknown function of OMP are
      discussed. To test the possibility that OMP might serve a mitogenic role in the
      OE, recombinant OMP was added to organotypic explant cultures of fetal olfactory
      mucosa. Addition of OMP resulted in a dose-dependent increase in the density of
      bromodeoxyuridine-positive cells in the cultures, with a 50% increase occurring
      at the plateau OMP concentration of 25 pM.

PMID- 9514527
TI  - Influence of GB virus C viraemia on the clinical, virological and histological
      features of early hepatitis C-related hepatic disease.
AB  - BACKGROUND/AIMS: GB virus C is a newly described RNA virus. The aims of this
      study were to determine the prevalence of GB virus C infection in patients with
      chronic type C hepatitis and to examine the clinical, virological and
      histological features in hepatitis C and GB virus C co-infected patients.
      METHODS/RESULTS: One hundred and sixty patients with hepatitis C infection were
      studied. GBV-C RNA was detected in 33/160 (20.6%) patients; co-infected patients
      with hepatitis C and GB virus C infection were significantly younger (p=0.04). No
      difference was found between the two groups according to gender and biochemical
      parameters. Seventy-two of the 160 patients, for whom a liver tissue specimen
      taken simultaneously with the serum was available and who had compensated liver
      disease, were studied separately. The source of infection, duration of infection,
      HCV genotype and HCV RNA concentrations did not differ between 15/72 patients
      with dual infection and 57/72 with hepatitis C infection alone. Patients with co
      infection had significantly higher degrees of portal and periportal inflammation
      (p=0.0006 and 0.01, respectively). No difference was observed in parenchymal
      activity score or extent of fibrosis. CONCLUSIONS: These results indicate a
      relatively high prevalence of GB virus C infection in younger patients with
      chronic hepatitis C, suggesting a common route of transmission. Although GB virus
      C co-infection does not alter the biochemical and virological profile of patients
      with HCV hepatitis, there is an association between GB virus C and hepatitis C
      viraemia and portal and periportal inflammation.

PMID- 9514528
TI  - Lack of evidence for GB virus C/hepatitis G virus replication in peripheral blood
      mononuclear cells.
AB  - BACKGROUND/AIMS: The recently identified hepatitis G virus (HGV) has been found
      to be common in patients with various forms of chronic liver disease,
      particularly chronic hepatitis C. However, replication sites of this new viral
      agent have not been studied. METHODS: We searched for the presence of HGV RNA in
      peripheral blood mononuclear cells and serum samples from nine chronic hepatitis
      C patients coinfected with hepatitis G virus. The presence of negative viral RNA
      strands was determined by strand-specific Tth-based assay which was optimized on
      synthetic template. RESULTS: All peripheral blood mononuclear cell samples were
      negative for the presence of the HGV RNA minus strand and only five were positive
      for the presence of the positive strand, albeit at a low level of 10-10(2)
      genomic equivalents/10(6) cells. CONCLUSIONS: These findings imply that hepatitis
      G virus does not replicate in peripheral blood mononuclear cells, at least in the
      population of HCV/HGV coinfected patients.

PMID- 9514529
TI  - Favorable response to lymphoblastoid interferon-alpha in children with chronic
      hepatitis C.
AB  - BACKGROUND/AIMS: We investigated the efficacy of interferon therapy for the
      treatment of children with chronic hepatitis C virus infection. METHODS: Twenty
      four out of 26 children completed the 6-month treatment with lymphoblastoid
      interferon-alpha and were followed for 12 months or longer. Response to
      interferon therapy was defined by assaying for circulating HCV-RNA, using a
      nested PCR, at 6-month intervals after the end of the therapy. RESULTS: At the
      end of treatment circulating HCV-RNA was undetectable in 18/24 patients and at 6
      months in 12/24. Ten of these 12 primary responders have remained virus free for
      more than 2 years. One patient remained negative at 12 months. The remaining
      patient relapsed at 12 months. At 24 months 10 of 18 patients tested negative for
      HCV-RNA. Serum alanine aminotransferase was normal in 11/24 patients at the end
      of treatment, at 6 months 12/24 were normal, and at 12 months 11/12 were normal.
      In eight children with sustained response, repeated liver biopsies revealed a
      reduction in Knodell's scores for inflammation in the hepatic lobules and in the
      portal areas. In three of them neither plus nor minus strand of HCV-RNA was
      detectable in the liver tissue. Responders had a significantly lower level of
      viremia than non-responders. Side effects of interferon including fever, hair
      loss, neutropenia, and thrombocytopenia were not serious enough to warrant
      cessation of interferon treatment. CONCLUSIONS: Interferon therapy in children
      with chronic hepatitis C may be beneficial as evaluated by sustained loss of
      viremia as well as by primary response.

PMID- 9514531
TI  - Randomised controlled double-blind trial of the calcium channel antagonist
      amlodipine in the treatment of acute alcoholic hepatitis.
AB  - BACKGROUND/AIMS: Calcium channel blockers have a hepatoprotective action in
      animal models of alcohol-induced liver injury but their effect in alcoholic liver
      disease in humans has not been previously investigated. We have conducted a
      randomised, placebo-controlled trial to investigate the possible benefit of the
      calcium channel blocker amlodipine in terms of 4-week survival in hospitalised
      patients with severe acute alcoholic hepatitis. METHODS: Sixty-two patients with
      acute alcoholic hepatitis were randomised to receive 5-10 mg amlodipine each day
      for 1 year or an identical capsule containing placebo. In 36 (58%), acute
      alcoholic hepatitis was confirmed on biopsy and in the remainder on clinical and
      laboratory criteria. There were no statistically significant differences in
      clinical characteristics and disease severity in the treated and placebo groups.
      RESULTS: Of the 32 patients receiving amlodipine, there were six deaths (19%) in
      the first 4 weeks compared with seven (23%) of the placebo patients (p=0.329).
      Causes of death were similar in the amlodipine and control groups, with liver
      failure predominant. Analysis by the Cox proportional hazards model after
      adjustment for other prognostic factors showed survival was not significantly
      influenced by active treatment (p=0.07). One patient in each group was withdrawn
      because of the development of hypotension, but this did not recur on
      reintroduction of the capsules. CONCLUSIONS: This study shows that calcium
      channel blockers are well tolerated with few side effects in advanced alcoholic
      liver disease, but there is no conclusive evidence from this study that calcium
      channel blockers are helpful in the treatment of alcoholic hepatitis.

PMID- 9514530
TI  - Interferon induces insulin resistance in patients with chronic active hepatitis
      C.
AB  - AIM/METHODS: To elucidate the metabolic effect of interferon alpha, the following
      tests were performed on 14 patients with chronic active hepatitis C before and
      after interferon therapy (6 million units/day for 2 weeks): (1) oral glucose
      tolerance tests to measure insulin secretion; (2) euglycemic hyperinsulinemic
      clamp with oral glucose load to measure peripheral and hepatic insulin
      sensitivity (splanchnic glucose uptake); and (3) measurements of plasma levels of
      glucoregulatory hormones. RESULTS: The oral glucose tolerance test showed that a
      2-week treatment with interferon did not induce apparent change in plasma glucose
      and insulin profiles. Nevertheless, interferon therapy worsened insulin-mediated
      glucose uptake in the peripheral tissues by 17% from 44.4+/-3.2 to 37.3+/-3.0
      micromol x kg(-1) x min(-1) (p<0.05). Furthermore, interferon therapy
      significantly decreased splanchnic glucose uptake by 38% from 47+/-2% to 29+/-3%
      (p<0.01). No changes were noted for plasma glucoregulatory hormones, such as
      epinephrine, norepinephrine, cortisol and growth hormone, after interferon
      therapy. CONCLUSIONS: These results indicate that interferon therapy for 2 weeks
      induces insulin resistance in the splanchnic, as well as peripheral tissues, in
      patients with chronic active hepatitis C. Therefore, more careful observation may
      be needed during interferon therapy in subjects with impaired glucose tolerance.

PMID- 9514532
TI  - Hyperventilation restores cerebral blood flow autoregulation in patients with
      acute liver failure.
AB  - BACKGROUND/AIMS: In patients with acute liver failure loss of cerebral blood flow
      autoregulation may result from cerebral vasodilatation. Since arterial hypocapnia
      induces cerebral vasoconstriction, we investigated whether cerebral blood flow
      autoregulation could be reestablished by mechanical hyperventilation. METHODS:
      Seven consecutive patients (median age 45, range 30-50 years) with acute liver
      failure and hepatic encephalopathy stage IV entered the study. They were all
      maintained on mechanical ventilation. Cerebral blood flow autoregulation was
      evaluated by using transcranial Doppler sonography to assess mean flow velocity
      (Vmean) in the middle cerebral artery, during a rise in mean arterial pressure by
      norepinephrine infusion (0.5-10 microg/h). The patients were subsequently
      hyperventilated for 15 min before cerebral blood flow autoregulation was re
      evaluated in the same mean arterial pressure range. RESULTS: At baseline PaCO2
      (4.0 (3.5-4.9)kPa), all patients had impaired cerebral blood flow autoregulation
      as Vmean increased from 47 (30-78) to 68 (49-107) cm x s(-1) (p<0.05), as MAP was
      raised from 82 (60-88) to 106 (89-123) mmHg. During hyperventilation, five of
      seven patients restored cerebral autoregulation as Vmean remained unchanged at 51
      (45-70) cm x s(-1) during a rise in MAP from 84 (65-94) to 110 (89-130) mmHg.
      Cerebral blood flow autoregulation was not restored in two patients, but
      hyperventilation reduced the slope of the mean arterial pressure-Vmean
      correlation. These two patients had renal failure and were treated with
      intermittent hemodialysis. CONCLUSIONS: Cerebral blood flow autoregulation was
      restored by hyperventilation in five of seven patients with acute liver failure,
      indicating that cerebral vasodilatation is of pathophysiological importance in
      dysregulation of cerebral circulation in acute liver failure.

PMID- 9514533
TI  - Effects of the endothelin receptor antagonist TAK-044 on hepatocyte element
      alterations in the ischemic-reperfused liver in Beagle dogs.
AB  - BACKGROUND/AIMS: This study was designed to investigate elemental alterations of
      subcellular organelles (cytoplasm, nucleus, mitochondria) after ischemia of the
      liver, and the effects of the pre-ischemic administration of an endothelin
      ETA/ETB receptor antagonist (TAK-044) on subcellular elements. METHODS: We
      determined serial changes in subcellular elements by X-ray microanalysis using
      liver biopsy specimens, and we compared the liver functions of a control and a
      TAK-044-treated group of Beagle dogs, before and after 70% partial ischemia (60
      min). TAK-044 was given intravenously at a dose of 3 mg/kg before ischemia.
      RESULTS: In the control, the Ca concentration in the cytoplasm showed a slight
      increase after ischemia and a marked increase immediately after reperfusion. It
      returned to approximately pre-ischemic levels at 6 h after reperfusion. In
      contrast, in the TAK-044 group, the increase was significantly suppressed. The
      changes in Na and Cl, which increased in parallel with Ca, were also suppressed
      in the TAK-044 group. The alterations in K were opposite to those Ca. These
      changes were also suppressed to a significant degree in the TAK-044 group.
      Elemental alterations in the nucleus and mitochondria were similar to those in
      the cytoplasm in both the control and TAK-044 groups. The changes in the liver
      functions and the electron microscopic findings supported the differences in
      serial changes in subcellular elements between the two groups. CONCLUSIONS: TAK
      044 exhibited a hepatoprotective effect on ischemia-reperfusion injury from the
      aspect of subcellular elemental dynamics and liver functional and morphologic
      changes.

PMID- 9514534
TI  - Increased nitric oxide production in the liver in the perioperative period of
      partial hepatectomy with Pringle's maneuver.
AB  - BACKGROUND/AIMS: There is no evidence that nitric oxide is produced in the liver
      during ischemia/reperfusion injury. This study examined the production of nitric
      oxide and inducible nitric oxide synthase in patients undergoing partial
      hepatectomy. METHODS: Twenty patients undergoing partial hepatectomy with only
      Pringle's maneuver were included. Peripheral blood was taken 1 day before the
      operation, during the operation (just after laparotomy and the first and last
      Pringle's maneuver) and 1 and 3 days after the operation, for measurement of
      plasma nitrate/nitrite, endotoxin and cytokine levels. Blood was also sampled
      from hepatic veins after Pringle's maneuver. Two liver specimens were taken from
      each patient, one before ischemia and one after partial hepatectomy, for the
      detection of inducible nitric oxide synthase. RESULTS: Average nitrate reached a
      maximum (33.5+/-3.4 micromol/l) after the final clamp (hepatic venous level). The
      increase in nitrate level during the operation correlated with the total duration
      of clamping. Endotoxin and interleukin-6 levels increased in a similar manner to
      nitrate levels, but tumor necrosis factor-alpha and interleukin-1 beta levels did
      not. In liver specimens taken after partial hepatectomy from patients, inducible
      nitric oxide synthase mRNA and protein were detected. CONCLUSIONS: Nitric oxide
      was produced in livers during ischemia/reperfusion injury and inducible nitric
      oxide synthase was involved in nitric oxide production.

PMID- 9514535
TI  - Differential Ca2+ signaling in neonatal and adult rat hepatocyte doublets.
AB  - BACKGROUND/AIMS: Intracellular Ca2+ ([Ca2+]i) is important in various cellular
      functions, including cellular proliferation and differentiation. To elucidate the
      relationship between [Ca2+]i oscillations and physiological hepatocyte
      proliferation, phenylephrine-evoked [Ca2+]i responses were sequentially
      investigated using short-term cultured hepatocyte doublets obtained from 1-, 3-,
      6- and 8-week-old rats. METHODS/RESULTS: DNA synthesis in hepatocytes, determined
      by BrdU incorporation, was approximately 20% in 1-week-old rats, and decreased to
      <1% as the rats aged. Correspondingly, [Ca2+]i responses evoked by 10 micromol/l
      phenylephrine in hepatocyte doublets shifted from transient to sinusoidal-type
      [Ca2+]i oscillations and then to a sustained increase in [Ca2+]i, followed by a
      gradual return to baseline. The incidence of [Ca2+]i oscillations was 100+/-0.0%,
      83.3+/-16.7%, 38.7+/-0.6% and 5.5+/-5.0% in 1-, 3-, 6- and 8-week-old rats,
      respectively. Removal of extracellular Ca2+ did not abolish [Ca2+]i oscillations,
      indicating that [Ca2+]i oscillations were caused primarily by Ca2+ mobilization
      from internal sites of the cells. The [Ca2+]i level in each of the adjacent cells
      was synchronous in sustained increase in [Ca2+]i, but asynchronous in [Ca2+]i
      oscillations. In proliferating doublets obtained from 1-week-old rats, the
      frequency of oscillations increased in a dose-dependent manner for phenylephrine
      concentrations of 1 to 100 micromol/l. CONCLUSIONS: Phenylephrine-evoked [Ca2+]i
      oscillations were directly related to hepatocyte proliferation and were mediated
      by frequency modulation. These results suggest that phenylephrine-evoked [Ca2+]i
      oscillations may contribute to cell-cycle progression of hepatocytes in
      physiological liver growth.

PMID- 9514536
TI  - Membrane-type matrix metalloproteinase-1(MT1-MTP) gene is overexpressed in highly
      invasive hepatocellular carcinomas.
AB  - BACKGROUND/AIMS: The matrix metalloproteinase (MMP) family play important roles
      in the invasion of cancer cells by degrading the extracellular matrices. The
      current study was designed to determine the expression pattern of membrane-type
      matrix metalloproteinase-1 (MT1-MMP) in hepatocellular carcinomas and its
      participation in invasion potential. METHODS: MT1-MMP mRNA expression was
      examined in 25 human hepatocellular carcinoma specimens using Northern blot, and
      the correlation to clinicopathological features was evaluated. In situ
      hybridization and immunohistochemistry were performed to study the localization
      and the cells responsible for the production. RESULTS: Northern blot analysis
      revealed high levels of MT1-MMP mRNA expression in tumorous portions in all
      cases, whereas in non-tumorous portions moderate or faint expression was evident
      in 22/25 cases. In 21/25 cases, the expression levels in tumorous portion were
      higher than those in non-tumorous portion. In particular, hepatocellular
      carcinoma with capsule infiltration demonstrated significantly higher expression
      than those without (p<0.05). In situ hybridization and immunohistochemical study
      revealed MT1-MMP transcripts and proteins in cancer cells and stromal cells,
      respectively. MT1-MMP positive cells were preferentially observed in the invading
      border of tumor nests. The MMP-2 transcript showed a similar pattern to that of
      MT1-MMP by in situ hybridization. CONCLUSION: The present study showed that the
      MT1-MMP gene is strongly expressed in hepatocellular carcinoma cells and is
      involved in the invasion potential of hepatocellular carcinoma, and also that MT1
      MMP may be one of the key molecules responsible for the invasion potential of
      hepatocellular carcinoma. Furthermore, the evidence suggests that MT1-MMP and MMP
      2 cooperate in the process of cancer invasion.

PMID- 9514537
TI  - The stereoisomers quinine and quinidine exhibit a marked stereoselectivity in the
      inhibition of hepatobiliary transport of cardiac glycosides.
AB  - BACKGROUND/AIMS: Certain basic (cationic) drugs are known to interact with the
      hepatic transport, and renal and/or biliary clearance of cardiac glycosides. The
      mechanisms behind these interactions are not fully understood. In the present
      study our aim was to investigate the effects of the two diastereomers, quinidine
      and quinine, as well as the calcium antagonist verapamil, on the hepatobiliary
      elimination of digoxin and ouabain in the isolated perfused rat liver. METHODS:
      Livers from male, fasting Wistar rats were perfused by recirculation of Krebs
      Henseleit bicarbonate buffer supplemented with 1% BSA. Disposition of digoxin or
      ouabain was studied at an initial perfusion medium concentration (Ci) of 100 or
      10 nmol/l for digoxin and a Ci of 30 micromol/l for ouabain. The Ci of quinine,
      quinidine or verapamil was 50 micromol/l. Concentrations of the drugs in
      perfusion medium and bile were followed up to 2 h. RESULTS: A marked reduction in
      the initial medium disappearance rate of digoxin and ouabain by quinine was
      found, whereas quinidine did not affect the hepatic disposition of the cardiac
      glycosides. The stereoselective inhibition of digoxin and ouabain clearance by
      quinine, and not by quinidine, was shown to be due to an effect on the hepatic
      uptake level rather than on the metabolic conversion and/or the biliary excretion
      steps. An allosteric type of inhibition by the basic drugs, exerted from the
      inside of the cells, is inferred. This interaction may occur at the sinusoidal
      plasma membrane on the level of multi-specific carrier proteins for cardiac
      glycosides and cationic drugs, as cloned recently by various groups. CONCLUSIONS:
      A marked stereoselective difference was found in the effect of the stereoisomers
      quinidine and quinine on the hepatic uptake of digoxin and ouabain, quinine being
      the potent inhibitor.

PMID- 9514538
TI  - Role for PKC alpha and PKC epsilon in down-regulation of CFTR mRNA in a human
      epithelial liver cell line.
AB  - BACKGROUND/AIMS: In the liver, intrahepatic biliary cells are the sole site of
      expression of the cystic fibrosis transmembrane conductance regulator, the
      product of the cystic fibrosis gene. We examined the regulation of cystic
      fibrosis transmembrane conductance regulator gene expression by protein kinase C
      in the recently characterized human liver epithelial BC1 cell line which
      expresses, at early confluence, both biliary (cystic fibrosis transmembrane
      conductance regulator, cytokeratin 19) and hepatocytic (albumin) specific
      markers. METHODS: Expression of the cystic fibrosis transmembrane conductance
      regulator was examined at the mRNA level by Northern blot, reverse transcription
      polymerase chain reaction and nuclear run-on assays and at the protein level by
      Western blotting. The functionality of this protein was tested by measurement of
      chloride efflux. Protein kinase C isotype expression and cytosol-to-membrane
      translocation were analysed by Western blotting. RESULTS: 1) Phorbol ester down
      regulated cystic fibrosis transmembrane conductance regulator mRNA expression in
      a time- and dose-dependent manner through a post-transcriptional mechanism with
      concomitant inhibition of stimulated chloride efflux. 2) Phorbol ester also
      activated protein kinase C as indicated by the cytosol-to-membrane translocation
      of both protein kinase C alpha and epsilon the two major protein kinase C
      isotypes expressed by BC1 cells. 3) Further, maximal down-regulation of the
      cystic fibrosis transmembrane conductance regulator mRNA by the phorbol ester was
      inhibited by H7 and by GF 109203X, two known protein kinase C inhibitors.
      CONCLUSIONS: These findings provide the first evidence for phorbol ester-induced
      down-regulation of cystic fibrosis transmembrane conductance regulator mRNA
      expression in a human liver epithelial cell line and point to a role for the
      classical protein kinase C alpha and the novel protein kinase C epsilon in this
      process.

PMID- 9514539
TI  - Expression of epithelial-cadherin, alpha-catenin and beta-catenin during human
      intrahepatic bile duct development: a possible role in bile duct morphogenesis.
AB  - BACKGROUND/AIMS: Cell adhesion molecules play an important role in the
      morphogenesis of developing organs. However, little is known about their
      expression during intrahepatic bile duct development. METHODS: We
      immunohistochemically investigated the expression of E-cadherin (E-Cad), alpha
      catenin (A-Cat) and beta-catenin (B-Cat) during human intrahepatic bile duct
      development, using 31 fetal livers of various gestational ages. The developmental
      stages of bile ducts were classified into the ductal plate, migrating biliary
      cells (remodeling stage), and immature bile ducts (remodeled stage). RESULTS: E
      Cad was broadly and strongly expressed in the ductal plate with a cytoplasmic
      pattern, heterogeneously and weakly expressed in the migrating biliary cells with
      a cytoplasmic pattern, and broadly and strongly expressed in immature bile ducts
      with a membranous pattern. A-Cat was broadly and strongly expressed in the ductal
      plate with a membrane pattern, broadly and moderately expressed in the migrating
      biliary cells with a membranous pattern, and broadly and strongly expressed in
      immature bile ducts with a membranous pattern. In contrast, expression of B-Cat
      was weak or slight in the ductal plate, but B-Cat was expressed broadly and
      strongly with a membranous pattern in migrating biliary cells and in immature
      bile ducts. Immature hepatocytes rarely expressed E-Cad and A-Cat, but expressed
      B-Cat with a membranous pattern throughout development. CONCLUSIONS: These
      results suggest that E-Cad, A-Cat and B-Cat are involved in the normal
      developmental morphogenesis of human intrahepatic bile ducts.

PMID- 9514540
TI  - Urinary 7alpha-hydroxy-3-oxochol-4-en-24-oic and 3-oxochola-4,6-dien-24-oic acids
      in infants with cholestasis.
AB  - BACKGROUND/AIMS: Urinary 3-oxo-delta4 bile acids have been detected in infants
      who ultimately died of liver disease. We used qualitative and quantitative
      methods to compare urinary 3-oxo-delta4 bile acids in liver disease, determining
      their composition and evaluating the prognostic implication in patients of
      various ages with various liver diseases. METHODS: Gas chromatography-mass
      spectrometry was used to measure 3-oxo-delta4 bile acids in the urine of patients
      and healthy controls. RESULTS: Patients with a deficiency of 3-oxo-delta4-steroid
      5beta-reductase and acute hepatic failure exhibited a significantly higher
      percentage of 3-oxo-delta4 bile acids in total bile acids in urine than the
      healthy controls or other patient groups, including those with neonatal
      cholestasis or biliary atresia (p<0.0001). The urinary 3-oxo-delta4 bile acids in
      patients with 3-oxo-delta4-steroid 5beta-reductase deficiency who had a poor
      prognosis were mainly 7alpha-hydroxy-3-oxochol-4-en-24-oic acid and 3-oxochola
      4,6-dien-24-oic acid. CONCLUSIONS: Our results indicate that an increase in the
      7alpha-hydroxy-3-oxochol-4-en-24-oic acid and 3-oxochola-4,6-dien-24-oic acid in
      the urine of patients with hepatobiliary disease indicates a poor prognosis.

PMID- 9514541
TI  - Insulin secretory capacity and the regulation of glucagon secretion in diabetic
      and non-diabetic alcoholic cirrhotic patients.
AB  - BACKGROUND/AIMS: Insulin secretion is increased in cirrhotic patients without
      diabetes but decreased in cirrhotic patients with diabetes. Increased glucagon
      secretion is found in both groups. Our aim was to determine: 1) whether
      alterations in insulin secretion are due to changes in maximal secretory capacity
      or altered islet B-cell sensitivity to glucose, and 2) whether regulation of
      glucagon secretion by glucose is disturbed. METHODS: Insulin, C-peptide and
      glucagon levels were measured basally and during 12, 19 and 28 mmol/l glucose
      clamps, and in response to 5 g intravenous arginine basally and after 35 min at a
      glucose of 12, 19 and 28 mmol/l in 6 non-diabetic alcoholic cirrhotic patients,
      six diabetic alcoholic cirrhotic patients and six normal controls. RESULTS:
      Fasting insulin, and C-peptide levels were higher in cirrhotic patients than
      controls but not different between diabetic and non-diabetic patients. C-peptide
      levels at t=35 min of the clamp increased more with glucose concentration in non
      diabetic cirrhotic patients than controls; there was little increase in diabetic
      cirrhotic patients. At a blood glucose of approximately 5 mmol/l the 2-5 min C
      peptide response to arginine (CP[ARG]) was similar in all groups, but enhancement
      of this response by glucose was greater in non-diabetic cirrhotic patients and
      impaired in diabetic cirrhotic patients. Maximal insulin secretion (CP(ARG) at 28
      mmol/l glucose) was 49% higher in the non-diabetic cirrhotic patients than
      controls (p<0.05); in diabetic cirrhotic patients it was 47% lower (p<0.05). The
      glucose level required for half-maximal potentiation of (CPARG) was not different
      in the three groups. Cirrhotic patients had higher fasting glucagon levels, and a
      greater 2-5-min glucagon response to arginine, which was enhanced by concomitant
      diabetes (p<0.001 vs controls). Suppression of plasma glucagon by hyperglycaemia
      was markedly impaired in diabetic cirrhotic patients (glucagon levels at 35 min
      of 28 mmol/l glucose clamp: diabetics, 139 x/divided by 1.25 ng/l, non-diabetic
      cirrhotic patients, 24 x/divided by 1.20, controls, 21 x/divided by 1.15,
      p<0.001). Suppression of arginine-stimulated glucagon secretion by glucose was
      also impaired in diabetic cirrhotic patients, and to a lesser extent in non
      diabetic cirrhotic patients. CONCLUSIONS: Insulin secretory abnormalities in
      diabetic and non-diabetic cirrhotic patients are due to changes in maximal
      secretory capacity rather than altered B-cell sensitivity to glucose. The
      exaggerated glucagon response to arginine in alcoholic cirrhotic patients is not
      abolished by hyperglycaemia/hyperinsulinaemia. In diabetic alcoholic cirrhotic
      patients, the inhibitory effect of glucose on basal glucagon secretion is also
      markedly impaired.

PMID- 9514542
TI  - Endoscopic sclerotherapy with fibrin glue as compared with polidocanol to prevent
      early esophageal variceal rebleeding.
AB  - BACKGROUND/AIMS: Endoscopic sclerotherapy is of proven benefit for patients after
      esophageal variceal bleeding, but is associated with substantial local and
      systemic complications. Since fibrin glue is a promising agent for endoscopic
      sclerotherapy of esophageal varices, we compared its safety and efficacy in
      patients after esophageal variceal bleeding. PATIENTS AND METHODS: In a
      randomized, controlled trial, 36 patients with an acute episode of variceal
      bleeding were endoscopically treated with either polidocanol (18 patients) or
      fibrin glue (18 patients) by intravariceal injections within 12 h of admission.
      Tissue compatibility, incidence of various complications, episodes of rebleeding
      and overall survival rates were investigated. RESULTS: Rebleeding, especially
      from enrollment to day 28, was less common in the fibrin group (p=0.046), and all
      patients treated with fibrin glue survived for more than 28 days, whereas five
      patients treated with polidocanol died within this period. The incidence of
      sclerotherapy-induced ulcers was significantly lower in the fibrin group than in
      the polidocanol group (p=0.001), and major complications such as perforation or
      ulcer bleeding were observed only in the polidocanol group. There were no
      complications in any group due to activation of systemic coagulation,
      fibrinolysis or clinically relevant pulmonary embolization. CONCLUSIONS: We
      conclude that fibrin glue is an efficient and safe agent for endoscopic
      sclerotherapy of bleeding esophageal varices, especially in the immediate
      posthemorrhagic period.

PMID- 9514543
TI  - Herbal medicine Sho-saiko-to (TJ-9) prevents liver fibrosis and enzyme-altered
      lesions in rat liver cirrhosis induced by a choline-deficient L-amino acid
      defined diet.
AB  - BACKGROUND/AIM: A herbal medicine, Sho-saiko-to (TJ-9), has recently been orally
      administered to patients with chronic liver disease in Japan and has been
      reported to inhibit the development of hepatocellular carcinoma. The aim of this
      study was to investigate whether TJ-9 has an inhibitory effect on the development
      of preneoplastic lesions and liver fibrosis in rats. METHODS: The effects of the
      TJ-9 were examined using the choline-deficient L-amino acid-defined (CDAA) diet
      induced liver fibrosis model in 16-week-old male Wistar rats. RESULTS: TJ-9 (1%
      w/w) prevented fibrosis, as indicated by reduced hydroxyproline content in the
      liver and inhibition of the increase in a serum marker of fibrosis (hyaluronic
      acid), without reducing the increase in serum alanine aminotransferase and
      aspartate aminotransferase. TJ-9 also reduced the expression of type III
      procollagen alpha 1 mRNA in the liver, as well as the proliferation of
      myofibroblast-like cells (activated stellate cells, activated Ito cells).
      Furthermore, TJ-9 reduced the number of preneoplastic lesions, detected as enzyme
      altered (glutathione S-transferase placental form-positive) lesions, in the
      liver. CONCLUSIONS: These results indicate that the herbal medicine Sho-saiko-to
      (TJ-9) prevents fibrosis as well as preneoplastic lesions, not by inhibiting
      hepatocyte cell death but by inhibiting the activation of stellate cells, which
      are considered to be the main collagen-producing cells, leading to a reduction in
      the development of preneoplastic lesions.

PMID- 9514544
TI  - Role of nitric oxide in extracellular nucleotide-induced contractile status of
      assorted vessels including parts of the portal vasculature.
AB  - BACKGROUND/AIMS: The resistance of portal vein and hepatic artery plays an
      important role in the regulation of the circulatory status in the liver, but the
      regulatory mechanisms for these hepatic vessels have still to be elucidated. The
      aim of this study was to discover the tonus regulation of the hepatic
      vasculature. METHODS: The effects of adenosine, adenosine 5'-monophosphate,
      adenosine 5'-diphosphate, adenosine 5'-triphosphate and uridine triphosphate on
      the force generation of the portal vein, superior mesenteric artery, inferior
      caval vein and aorta of the rat were studied in vitro. Each vessel was removed
      and cut into 5-mm ring strips. The strips were fixed vertically between triangle
      hooks and incubated in organ baths containing Krebs-Henseleit solution. The
      change in vascular tension was continuously monitored by a force-displacement
      transducer and recorded isometrically with a polygraph. RESULTS: Adenosine 5'
      diphosphate and adenosine 5'-triphosphate induced relaxation of superior
      mesenteric artery and aorta precontracted with prostaglandin F2alpha dose
      dependently. The effects of adenosine 5'-diphosphate and adenosine 5'
      triphosphate were attenuated in the presence of N(G)-nitro-L-arginine, indicating
      nitric oxide dependency. In contrast, all these nucleotides dose-dependently
      induced contraction of the portal vein obtained from the hepatic hilus. N(G)
      nitro-L-arginine decreased the EC50 values for these metabolites. Interestingly,
      all the nucleotides failed to induce contraction of the inferior caval vein and
      the portal vein distal to the hepatic hilus. CONCLUSIONS: These results suggest
      that some purinoceptor-dependent pathway regulates contraction of the portal vein
      close to the hepatic hilus and elicits, in contrast, the relaxation of superior
      mesenteric artery and aorta. Nitric oxide may participate in the tonus regulation
      of hepatic vasculature.

PMID- 9514545
TI  - Liver transplantation in patients with non-biliary cirrhosis: prognostic value of
      preoperative factors.
AB  - BACKGROUND/AIM: The type of disease indicating liver transplantation is one of
      the most powerful predictors of postoperative survival. This may be an important
      problem in evaluating the prognostic significance of other factors when patients
      with liver diseases of very different nature are jointly studied. To minimize
      this bias, the present study aimed to investigate preoperative prognostic factors
      in liver transplantation only in patients with non-biliary cirrhosis. METHODS:
      Twenty-three preoperative standard clinical and laboratory variables were
      analyzed as possible prognostic factors in 162 patients receiving liver
      transplantation for non-biliary cirrhosis. Data for seven splanchnic and systemic
      hemodynamic variables were also analyzed in 55 patients. RESULTS: Using
      univariate analyses followed by a multivariate analysis, only preoperative blood
      urea nitrogen (BUN) reached statistical significance as an independent predictor
      of hospital survival; the survival rate at the end of hospitalization being 90%
      in patients with BUN< or =25 mg/dl and 65% in patients with BUN>25 mg/dl
      (p=0.0008). Similarly, preoperative BUN was the only variable independently
      predicting cumulative long-term survival, with an 87% survival probability at 1
      year and 73% at 4 years in patients with BUN< or =25 mg/dl, and 61% and 49%,
      respectively, in patients with BUN>25 mg/dl (p=0.0014). CONCLUSIONS: Renal
      function parameters are the most powerful preoperative predictors of survival
      after liver transplantation in patients with non-biliary cirrhosis. It is
      suggested that liver transplantation is indicated in these patients before marked
      renal dysfunction develops.

PMID- 9514546
TI  - The effects of liver transplantation and cyclosporine on bile formation and lipid
      composition: an experimental study in the rat.
AB  - BACKGROUND/AIMS: Hepatic graft dysfunction is a major management problem in the
      early post-liver transplantation period. Our aims were to study how liver
      transplantation per se affects bile formation, and to investigate the role of
      cyclosporine in the pathogenesis of early graft dysfunction. METHODS: Syngeneic
      liver transplantation used male Lewis rats. Two weeks after transplantation, the
      rats were randomly assigned to receive either daily subcutaneous injections of
      cyclosporine 10 mg/kg for 1 week (n=8), or daily saline injections (Placebo,
      n=8). 24-h bile collections were performed 18 h after the last injection. Eight
      non-transplanted rats served as controls. RESULTS: Liver transplantation per se
      (Placebo) significantly increased basal bile flow (51%), particularly that
      portion which was bile salt-independent flow (81%), but did not impair bile salt
      kinetics or biliary lipid composition. Cyclosporine reduced basal bile flow and
      bile salt-independent flow by 41% and 30%, respectively. Bile salt synthesis was
      52% suppressed, leading to a 22% decrease in the bile salt pool size. The
      recycling frequency of the bile salt pool was unaffected. The drug inhibited bile
      salt (37%) and phospholipid (23%) outputs; cholesterol secretion remained
      unaltered. This significantly elevated the cholesterol saturation of bile (25%).
      CONCLUSIONS: Liver transplantation per se is choleretic and does not impair bile
      formation or lipid composition in this inbred rat model. Parenteral
      administration of high-dose cyclosporine induces cholestasis by inhibiting bile
      salt secretion and BSIF. Bile salt synthesis is down-regulated and the bile salt
      pool size decreased. The drug adversely affects biliary lipid composition by
      differential inhibition of bile salt and phospholipid outputs relative to an
      unchanged cholesterol secretion.

PMID- 9514547
TI  - Early liver transplantation is crucial in children with liver disease and
      pulmonary artery hypertension.
AB  - BACKGROUND/AIMS: Early liver transplantation is crucial in children with liver
      disease and pulmonary artery hypertension. Some severe pulmonary vascular
      anomalies associated with portal hypertension disappear after isolated liver
      transplantation. Evolution of pulmonary artery hypertension due to plexogenic
      arteriopathy is controversial, as this association is still considered a
      contraindication to isolated liver transplantation. Outcome of pulmonary
      hypertension after isolated liver transplantation is reported in three patients
      with portal hypertension. METHODS: After echocardiographic diagnosis, the
      patients had a complete hemodynamic exploration, and two had a lung biopsy. After
      liver transplantation, the survivors had echocardiographic follow up and a second
      hemodynamic exploration. RESULTS: In two children, pulmonary pressures and
      resistances returned to near-normal values 1 and 6 years after successful
      isolated liver transplantation. The third patient, with the most severe
      arteriopathy, had to wait 1 year for a donor, and the attempted transplantation
      was complicated by ventricular tachycardia; death occurred 2 days after surgery.
      CONCLUSIONS: Liver transplantation can reverse pulmonary artery hypertension due
      to high pulmonary resistances complicating liver disease with portal
      hypertension, provided it is carried out at an early stage. Early detection of
      pulmonary hypertension by systematic echocardiography may thus be crucial in
      these children with portal hypertension.

PMID- 9514548
TI  - Images in hepatology. Hepatic pseudotumor in Osler-Weber-Rendu disease.

PMID- 9514549
TI  - The secretory function of the liver: new aspects of hepatobiliary transport.

PMID- 9514550
TI  - Interferon-alpha treatment of hepatitis C virus-associated mixed
      cryoglobulinemia.

PMID- 9514551
TI  - HCV/HGV coinfection and cryoglobulinemia.

PMID- 9514553
TI  - Selection bias in pain research.

PMID- 9514552
TI  - Immunosuppressive therapy for carbamazepine-induced hypersensitivity syndrome and
      hepatitis.

PMID- 9514554
TI  - Pathophysiology and treatment of opioid-related myoclonus in cancer patients.
AB  - Myoclonus occasionally occurs in the perioperative setting and in patients on
      chronic opioid therapy. It appears to be dose-related in a unpredictable manner.
      Different mechanisms have been proposed to explain the occurrence of a series of
      neuromuscular disturbances probably sharing final common pathways. A
      neuroexcitatory opioid metabolite accumulation has been proposed to have a
      relevant role in determining myoclonus in patients treated with chronic opioid
      therapy for cancer pain, especially in the presence of renal impairment. The
      neurological status, previous oncologic treatment and concomitant therapy with
      neuroleptic drugs, the metabolic and hydration status should also have been
      considered. Adjuvant drugs, such as benzodiazepines or dantrolene may avoid the
      reduction of the opioid dose while maintaining an acceptable analgesia. Current
      practice suggests a change in opioid when pain control is not obtained at opioid
      doses resulting in unacceptable adverse effects, including myoclonus and
      hyperalgesia. A change in the type of opioid may be useful in patients who
      develop severe central adverse effects, even if these patients appear to have
      normal renal function or hydration status.

PMID- 9514555
TI  - Colchicine treatment of the sciatic nerve reduces neurogenic extravasation, but
      does not affect nociceptive thresholds or collateral sprouting in neuropathic or
      normal rats.
AB  - The effect of topical colchicine treatment of the sciatic nerve on sciatic and
      saphenous nociceptive thresholds and neurogenic extra-vasation was investigated
      in normal and neuropathic rats. After a pilot investigation using several
      different concentrations of colchicine it was determined that treating the
      sciatic nerve with 5 mM colchicine did not usually affect the heat nociceptive
      threshold over the sciatic innervated plantar surface of the hindpaw. Mechanical
      nociception and motor function were also unchanged. Electrical stimulation of the
      sciatic nerve after intravenous injection of Evans blue dye causes extravasation
      of the dye in the cutaneous distribution of the nerve. The area and quantity of
      sciatic extravasation were measured 3 weeks after treating the sciatic nerve with
      colchicine. This treatment results in a marked loss of neurogenic extravasation,
      but there were no changes in the sciatic and saphenous mediated heat and
      mechanical nociceptive thresholds. The area of saphenous nociceptive innervation
      was mapped using pinch responses and saphenous neurogenic extravasation acutely
      after sciatic section. There was no change in the cutaneous distribution of
      saphenous nociceptive fibers when measured 3 weeks after the sciatic colchicine
      treatment. Some rats had their sciatic nerves transected immediately after
      colchicine treatment (5 and 50 mM) and the saphenous nociceptive thresholds and
      autotomy scores were followed postoperatively. Colchicine pretreatment of the
      sciatic nerve has no effect on the development of hyperalgesia or autotomy.
      Colchicine blocks axonal transport in peripheral nerve, including the orthograde
      transport of tachykinins, which probably explains its ability to induce prolonged
      reductions in sciatic neurogenic extravasation at concentrations that spare C
      fiber nociceptor function. Sciatic nerve colchicine treatment does not trigger
      nociceptive fiber collateral sprouting from the adjacent saphenous nerve, nor
      does it influence the development of hyperalgesia and autotomy behavior after
      sciatic transection.

PMID- 9514556
TI  - Learning to live with the pain: acceptance of pain predicts adjustment in persons
      with chronic pain.
AB  - When patients find their pain unacceptable they are likely to attempt to avoid it
      at all costs and seek readily available interventions to reduce or eliminate it.
      These efforts may not be in their best interest if the consequences include no
      reductions in pain and many missed opportunities for more satisfying and
      productive functioning. The purpose of this study was to examine acceptance of
      pain. One hundred and sixty adults with chronic pain provided responses to a
      questionnaire assessing acceptance of pain, and a number of other questionnaires
      assessing their adjustment to pain. Correlational analyses showed that greater
      acceptance of pain was associated with reports of lower pain intensity, less pain
      related anxiety and avoidance, less depression, less physical and psychosocial
      disability, more daily uptime, and better work status. A relatively low
      correlation between acceptance and pain intensity showed that acceptance is not
      simply a function of having a low level of pain. Regression analyses showed that
      acceptance of pain predicted better adjustment on all other measures of patient
      function, independent of perceived pain intensity. These results are preliminary.
      Further study will be needed to show for whom and under what circumstances,
      accepting some aspects of the pain experience may be beneficial.

PMID- 9514557
TI  - The activity of ON and OFF cells at the rostroventromedial medulla is modulated
      by vagino-cervical stimulation.
AB  - In anesthetized rats it was tested whether or not the activity of the ON and OFF
      cells within the rostral ventromedial medulla (RVM) is modulated by the
      mechanical stimulation of the uterine cervix (VS). ON cells were identified by an
      abrupt increase in their firing rate before the tail flick in response to a
      noxious heat. OFF cells were identified by a sudden decrease in their firing rate
      before the tail flick. All (27 out of 27) identified ON cells decreased their
      firing rate immediately after VS was applied. The effect of VS on the activity of
      the cells persisted for the entire stimulation period. On the other hand, all (19
      out of 19) identified OFF cells increased their firing rate immediately after VS.
      The effect of VS on the activity of these cells also persisted for the entire
      stimulation period. The activity of the neutral cells showed no change, neither
      during the application of noxious heat, nor during VS. These results suggest that
      the analgesic-like effect produced by VS can be mediated by the activity of the
      antinociceptive circuit at the RVM. Alternatively, it can be suggested that the
      afferent inflow from the genital tract can induce the activity of the
      antinociceptive circuit at RVM, either by projections to the periaqueductal gray
      matter or by direct projections to RVM.

PMID- 9514558
TI  - Anti-inflammatory interleukin-10 therapy in CCI neuropathy decreases thermal
      hyperalgesia, macrophage recruitment, and endoneurial TNF-alpha expression.
AB  - The chronic constriction injury model of mononeuropathy is a direct, partial
      nerve injury yielding thermal hyperalgesia. The inflammation that results from
      this injury is believed to contribute importantly to both the neuropathological
      and behavioral sequelae. This study involved administering a single dose (250 ng)
      of interleukin-10 (IL-10), an endogenous anti-inflammatory peptide, at the site
      and time of a chronic constriction injury (CCI) lesion to determine if IL-10
      administration could attenuate the inflammatory response of the nerve to CCI and
      resulting thermal hyperalgesia. In IL-10-treated animals, thermal hyperalgesia
      was significantly reduced following CCI (days 3, 5 and 9). Histological sections
      from the peripheral nerve injury site of those animals had decreased cell
      profiles immunoreactive for ED-1, a marker of recruited macrophages, at both
      times studied (2 and 5 days post-CCI). IL-10 treatment also decreased cell
      profiles immunoreactive for the pro-inflammatory cytokine tumor necrosis factor
      alpha (TNF-alpha) at day 2, but not day 5. Qualitative light microscopic
      assessment of neuropathology at the lesion site did not suggest substantial
      differences between IL-10 and vehicle-treated sections. The authors propose that
      initial production of TNF-alpha and perhaps other proinflammatory cytokines at
      the peripheral nerve lesion site importantly influences the long-term behavioral
      outcome of nerve injury, and that IL-10 therapy may accomplish this by
      downregulating the inflammatory response of the nerve to injury.

PMID- 9514560
TI  - Weight bearing of the limb as a confounding factor in assessment of mechanical
      allodynia in the rat.
AB  - Effect of weight bearing of the hindlimbs on the assessment of mechanically
      induced hindlimb withdrawal threshold was determined in intact rats and in rats
      with various pathophysiological conditions causing allodynia or hyperalgesia.
      Hindlimb withdrawal was elicited by applying a series of calibrated monofilaments
      to the plantar or the dorsal surface of the paw. During testing the rat was
      either in a restraint tube with hindlimbs hanging semi-extended without weight
      bearing or it was standing on a metal grid (bearing its own weight). In intact
      rats, the withdrawal thresholds were significantly lower when the stimulus site
      was the dorsal hairy skin rather than the plantar glabrous skin. Also, thresholds
      were significantly lower when the hindlimbs were not bearing weight. Following
      carrageenan-induced unilateral inflammation of the plantar paw or a tibial nerve
      cut there was a marked threshold decrease to test stimuli applied to plantar or
      dorsal paw, respectively, ipsilateral to the pathological condition in standing
      rats. However, when the hindlimbs were not weight bearing the unilateral
      threshold decrease was markedly attenuated (carrageenan-treated rats) or
      completely abolished (tibial cut). In contrast, in rats with a unilateral spinal
      nerve ligation the threshold decrease ipsilateral to the nerve lesion was highly
      significant independent of the weight bearing of the hindlimbs. The results
      indicate that weight bearing of hindlimbs is an important confounding factor in
      the assessment of tactile allodynia in rats.

PMID- 9514559
TI  - Systematic review of factors affecting the ratios of morphine and its major
      metabolites.
AB  - In a systematic review of 57 studies with information on 1232 patients we
      examined the effect of age, renal impairment, route of administration, and method
      of analysis on the ratios of morphine-3-glucuronide:morphine (M3G:M) and morphine
      6-glucuronide:morphine (M6G:M) and the relative concentrations of M3G and M6G.
      Across all studies the range of the ratios of metabolites to morphine was wide
      (0.001-504 for M3G:M, and 0-97 for M6G:M). Neonates produced morphine
      glucuronides at a lower rate than older children or adults. Metabolite ratios
      were higher in renal impairment. Routes of administration which avoided first
      pass metabolism (intravenous, transdermal, rectal, intramuscular, epidural and
      intrathecal) resulted in lower metabolite production than oral, buccal or
      sublingual. Metabolite production was similar for single and multiple dosing.
      There was no evidence of differences between methods of assay. There was a high
      correlation between the two glucuronide metabolites in spite of the different
      situations studied, supporting a single glucuronidating enzyme. Morphine was
      present in CSF at a fourfold higher concentration than the glucuronide
      metabolites.

PMID- 9514561
TI  - Experimental cranial pain elicited by capsaicin: a PET study.
AB  - Using a positron emission tomography (PET) study it was shown recently that in
      migraine without aura certain areas in the brain stem were activated during the
      headache state, but not in the headache free interval. It was suggested that this
      brain stem activation is inherent to the migraine attack itself and represents
      the so called 'migraine generator'. To test this hypothesis we performed an
      experimental pain study in seven healthy volunteers, using the same positioning
      in the PET scanner as in the migraine patients. A small amount of capsaicin was
      administered subcutaneously in the right forehead to evoke a burning painful
      sensation in the first division of the trigeminal nerve. Increases of regional
      cerebral blood flow (rCBF) were found bilaterally in the insula, in the anterior
      cingulate cortex, the cavernous sinus and the cerebellum. Using the same
      stereotactic space limits as in the above mentioned migraine study no brain stem
      activation was found in the acute pain state compared to the pain free state. The
      increase of activation in the region of the cavernous sinus however, suggests
      that this structure is more likely to be involved in trigeminal transmitted pain
      as such, rather than in a specific type of headache as was suggested for cluster
      headache.

PMID- 9514562
TI  - Temporal and qualitative properties of cold pain and heat pain: a psychophysical
      study.
AB  - Dorsal horn neurons that respond to noxious cold also respond to noxious heat,
      suggesting the hypothesis that pain evoked by temperature extremes, whether hot
      or cold, may be processed similarly in the CNS. In this study, we tested
      perceptual consequences of this hypothesis by comparing characteristics of heat
      and cold pain, as well as of innocuous warm and cool. Eight healthy subjects
      performed psychophysical tasks involving hot and cold cutaneous stimuli. Using a
      9-cm2 contact thermode, temperatures from -5 degrees to 48 degrees C were each
      applied for 30 s to the thenar eminence. Subjects gave continuous ratings of
      perceived temperature and pain intensity, using an electronic VAS. After each
      stimulus, subjects also reported the maximum stimulus intensity and
      unpleasantness, and chose appropriate words from a list of qualitative verbal
      descriptors. We found that larger temperature differences were needed in the
      noxious cold than in the noxious heat range to produce equal perceptual
      differences. Further, in the heat range, stimulus-response functions were steeper
      for noxious than for innocuous temperatures, whereas in the cold range, the
      opposite held true. The relative unpleasantness of heat pain did not differ from
      that of cold pain, but subjects used a wider range of qualitative words to
      describe cold pain. Perceived stimulus intensity was compared to temperature
      recordings from intradermal and skin surface thermocouples. Heat pain, cool and
      warmth appeared to depend on surface temperature, whereas cold pain was related
      to subcutaneous temperature, suggesting different receptors for noxious heat and
      noxious cold. These data, combined with results of human brain imaging and
      primate electrophysiological studies, suggest that the unpleasantness associated
      with both heat pain and cold pain is processed similarly in the CNS, whereas
      differential information about stimulus quality is preserved in the cerebral
      cortex.

PMID- 9514563
TI  - Peripheral antinociceptive effect of an adenosine kinase inhibitor, with
      augmentation by an adenosine deaminase inhibitor, in the rat formalin test.
AB  - This study examined the ability of an adenosine kinase inhibitor (5'-amino-5'
      deoxyadenosine; NH2dAD), an adenosine deaminase inhibitor (2'-deoxycoformycin),
      and combinations of these agents to produce a peripheral modulation of the pain
      signal in the low concentration formalin model. Drugs were administered in
      combination with 0.5% formalin, or into the contralateral hindpaw to test for
      systemic effects, and episodes of flinching behaviors determined.
      Coadministration of NH2dAD 0.1-100 nmol with formalin produced antinociception as
      revealed by an inhibition of flinching behaviors. This action was peripherally
      mediated as it was not seen following contralateral administration of the NH2dAD,
      and was due to accumulation of adenosine and activation of cell surface adenosine
      receptors as it was blocked by the adenosine receptor antagonist caffeine.
      Antinociception was intensity-dependent, as it was not seen when higher
      concentrations of formalin (0.75%, 1.5%) were used. The coadministration of the
      selective adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dimethylxanthine
      revealed the presence of an inhibitory tone of adenosine when the intrinsic
      antinociceptive effect of NH2dAD was obscured by the solvent or the stimulus
      intensity. 2'-Deoxycoformycin 0.1-100 nmol did not produce any intrinsic effect,
      but 100 nmol coadministered with low concentrations of NH2dAD, which lacked an
      intrinsic effect, augmented antinociception by NH2dAD. Again, this was a
      peripheral rather than a systemic response. The combined action of the adenosine
      kinase and deaminase inhibitors was completely reversed by coadministration of
      caffeine. Antinociception with NH2dAD is observed at higher concentrations of
      formalin in second trial experiments. This study demonstrates a peripheral
      antinociceptive action mediated by endogenous adenosine which accumulates
      following the peripheral inhibition of adenosine kinase; this action is due to
      activation of an adenosine A1 receptor.

PMID- 9514565
TI  - Mechanical hyperesthesia of human facial skin induced by tonic painful
      stimulation of jaw muscles.
AB  - The function of the somatosensory system in patients with painful
      temporomandibular disorders is still a matter of discussion. We wished to
      determine cutaneous sensitivity to innocuous mechanical stimuli in the orofacial
      region before, during (3 and 12 min) and after standardized experimental jaw
      muscle pain. Twelve healthy subjects were exposed to tonic infusion of hypertonic
      (5%) and isotonic (0.9%) saline into the masseter muscle. All subjects
      experienced moderate pain with hypertonic saline, and the area of self-reported
      pain increased significantly from 3 min after infusion start to 12 min after
      infusion start (mean +/- SEM: 115+/-49%; P < 0.05). The psychophysical ratings of
      punctate von Frey hair stimulation were significantly increased 12 min after
      start of hypertonic saline infusion as compared to baseline and post-baseline
      ratings at the site of infusion (50+/-10%; P < 0.05) and at two adjacent facial
      sites (18+/-7%, 37+/-9%; P < 0.05). In contrast, isotonic saline infusion was
      associated with a significant decrease in ratings at post-baseline as compared to
      baseline ratings. The psychophysical ratings of a stroking cotton swab
      stimulation were not significantly affected by infusion of saline. These results
      in a human model of jaw-muscle pain are comparable to animal studies
      demonstrating increased size of cutaneous receptive fields and increased
      responsiveness of brain stem neurons to cutaneous mechanical stimuli. Similar
      hyperexcitability changes may be part of the pathophysiological mechanisms
      involved in painful temporomandibular disorders.

PMID- 9514564
TI  - The effect of thalidomide treatment on vascular pathology and hyperalgesia caused
      by chronic constriction injury of rat nerve.
AB  - Tumor necrosis factor alpha (TNF) may be involved in the pathogenic mechanisms of
      neuropathic pain by affecting endothelial cells and by upregulation of receptor
      sensitivity in afferent nerve fibers. To test the hypothesis that TNF plays a
      role in the vascular changes and the pain-related behavior in an experimental
      painful neuropathy in rats produced by tying loosely constrictive ligatures
      around one sciatic nerve, we investigated the effect of thalidomide, a selective
      blocker of TNF-production in activated macrophages. In rats in which treatment
      with thalidomide was started preoperatively, there was diminished mechanical
      allodynia and thermal hyperalgesia during the early stage of the disease. TNF
      immunohistochemistry revealed reduced endoneurial immunoreactivity on day 5 post
      surgery as compared to sham-treated animals. The pathologic vascular changes were
      also reduced in thalidomide-treated rats. Starting treatment with thalidomide at
      a time point when hyperalgesia was already present did not alter the course of
      the pain-related behavior. We conclude that preemptive treatment with a substance
      that blocks production of TNF reduces pain-related symptoms and pathologic
      vascular changes in the chronic constriction injury model of neuropathic pain.

PMID- 9514566
TI  - Comments on editorials: Berkley, PAIN, 70 (1997) 1-2 and Gybels, PAIN, 70 (1997)
      103-107.

PMID- 9514567
TI  - Comments on Derbyshire, PAIN, 67 (1996) 210-211.

PMID- 9514568
TI  - Comments on Wang et al., PAIN, 67 (1996) 407-416.

PMID- 9514569
TI  - Comment on Egan and Krieger, PAIN, 69 (1997) 213-218.

PMID- 9514570
TI  - Clinical, microbiological and epidemiological aspects of Escherichia coli O157
      infection.
AB  - In the last decade infections caused by Escherichia coli O157:H7 and other
      verocytotoxigenic E. coli (VTEC) have emerged as a major public health concern in
      North America and in Europe, and increasingly in other areas of the world.
      Although absolute numbers of infections are low in comparison with other enteric
      pathogens such as Salmonella or Campylobacter, it is well-recognised that E. coli
      O157 can produce severe, potentially life-threatening, illness. As a consequence
      of this awareness, there has been a rapid expansion of our knowledge about these
      organisms and the diseases which they cause. In this article, the clinical,
      microbiological and epidemiological features of VTEC O157 infection are reviewed.

PMID- 9514571
TI  - Binding of complement subcomponent C1q to Streptococcus pyogenes: evidence for
      interactions with the M5 and FcRA76 proteins.
AB  - Binding of C1q, the first component of the complement system, to some human
      pathogens has been earlier reported. In the present study, direct binding of C1q
      to group A streptococci (GAS) of various serotypes as well as some other Gram
      positive and Gram-negative species was demonstrated. The interaction between C1q
      and GAS was investigated more in detail. In hot neutral extracts of a number of
      GAS strains two components of 64 and 52 kDa, respectively, bound C1q; alkaline
      and SDS extracts yielded the 52 kDa component as the main C1q-binding substance.
      Trypsin treatment of the SDS extracts of two GAS strains suggested the C1q
      binding component(s) to be of protein nature. C1q-binding material purified from
      the SDS extract of an avirulent strain, type T27, was separated in 12% SDS-PAGE
      and probed in Western blot with human C1q and fibrinogen, conjugated to horse
      radish peroxidase (HRP) as well as rabbit IgG antibodies complexed to HRP (PAP
      system). The 52 kDa component was non-reactive with fibrinogen or rabbit IgG.
      However, C1q-binding components purified from the alkaline extracts of two M
      positive strains revealed strong binding of either fibrinogen (type M5) or both
      fibrinogen and rabbit IgG (type M76); the molecular mass of these components. 55
      kDa and 43-40 kDa, respectively, was in agreement with the reported molecular
      mass of the M5 and FcRA76 proteins. Our findings suggest that C1q may interact
      with GAS through certain M-family proteins as well as by a so far unidentified
      surface factor of protein nature occurring in most GAS strains. The involvement
      of M-family proteins, regarded as virulence factors of these organisms, may
      suggest the interaction of GAS with C1q as biologically important.

PMID- 9514572
TI  - Intramammary immunization with live-attenuated Staphylococcus aureus protects
      mice from experimental mastitis.
AB  - Female mice were immunized by the intramammary route with live-attenuated
      Staphylococcus aureus according to different schedules and challenged with
      virulent S. aureus. Immunization in late pregnancy or early lactation induced a
      significant decrease (P <0.05) in the number of S. aureus CFU recovered from
      glands after the challenge and a significant increase (P <0.05) in the levels of
      milk and serum specific IgG and IgA antibodies. Mice immunized before pregnancy
      were not protected from S. aureus challenge. Immunization did not increase the
      number of somatic cells in milk when compared with control mice. Protection from
      S. aureus intramammary infection may be achieved if mice are locally immunized
      during late pregnancy or early lactation.

PMID- 9514573
TI  - Effect of Pasteurella haemolytica outer membrane proteins on bovine neutrophils.
AB  - The major outer membrane proteins (OMPs) isolated from Pasteurella haemolytica
      induce alterations of the biological activity of bovine polymorphonuclear
      leukocytes (PMNs). A dose-dependent reduction of the capacity of adherence to
      nylon wool in vitro was observed. OMPs also acted as chemotaxins at
      concentrations between 5 and 20 microg/ml. Concentrations lower than 5 microg/ml
      did not give considerable results. Preincubation with 5 microg/ml of OMPs led to
      modifications in the values of the phagocytic index and of intracellular killing,
      which were found to be diminished with respect to controls.

PMID- 9514574
TI  - Characterisation and molecular typing of Burkholderia pseudomallei: are disease
      presentations of melioidosis clonally related?
AB  - Eighteen cases of culture positive melioidosis caused by Burkholderia
      pseudomallei, were seen in four geographically separate communities in North
      Queensland, Australia. The genetic inter-relatedness of the clinical isolates
      were compared utilising random amplification of polymorphic DNA (RAPD) and
      multilocus enzyme electrophoresis (MEE). The isolates segregated into two groups
      that correlated with clinical presentation rather than geographical location.
      This is the first described association between the varied clinical presentations
      of this condition and specific molecular type. If proven on larger studies, this
      may further our understanding of the pathogenesis of this important condition.

PMID- 9514575
TI  - Lipopolysaccharide O-antigen expression and the effect of its absence on
      virulence in rfb mutants of Vibrio cholerae O1.
AB  - Using defined rfb mutants, defective in the biosynthesis of the O-antigen of the
      lipopolysaccharide (LPS), and monoclonal antibodies (MAbs) to the A, B and C LPS
      antigens, we have examined the distribution of the antigens and the effects of
      their loss. By immunogold electron microscopy, it has been possible to determine
      the relative amounts of the A, B and C antigens on Inaba and Ogawa cells,
      confirming previous studies based upon bacterial agglutination and
      hemagglutination inhibitions. These antigens are absent from rfb::Tn mutants
      selected as resistant to phages which have been shown to use the O-antigen as
      their receptor. These mutants were severely attenuated as measured by both LD50
      and their ability to compete with the wild-type parents when analyzed in the
      infant mouse cholera model. These mutants were unchanged in the export of cholera
      toxin or other secreted proteins but revealed an altered outer membrane protein
      profile. The competition defect suggested an effect on TCP (toxin-coregulated
      pilus). An analysis of the rfb::Tn mutants revealed that they were unable to
      assemble TCP on their surface, but the major subunit, TcpA, could be found as an
      intracellular pool. These mutants could be complemented back to wild-type using
      the cloned rfb region, implying that functional TCP assembly is dependent upon an
      intact LPS.

PMID- 9514576
TI  - Fucose-specific adhesins on germ tubes of Candida albicans.
AB  - Lectin-like adhesins of hyphal-form Candida albicans were investigated by
      conventional fluorescence microscopy, fluorescence microscopy with image
      analysis, spectrofluorimetry and flow cytometry. Labelling was done with
      neoglycoprotein probes consisting of sugars (fucose, mannose, glucose, galactose,
      lactose) covalently linked to bovine serum albumin (BSA), which itself was
      labelled with fluorescein. The fucose probe bound to both the yeast and germ-tube
      portions of hyphal-form cells, not especially at the tip, but in the adjacent
      region of the germ-tube portion. Probes with the other sugars did not label the
      hyphal-form cells. Fucose-probe binding to the cells was optimal at pH 5.0 in
      citrate buffer, and was a time-dependent reaction requiring 30-60 min and
      reaching saturation concentration at 100 microg ml(-1). Each hyphal-form cell of
      C. albicans grown in 199 medium was calculated to have about 2 x 10(7) fucose
      probe-binding sites. There appeared to be no requirement for Ca2+ or Mg2+ in
      binding. Binding of the fucose probe to the hyphal-form cells was higher at 37
      degrees C than at 22 degrees C or 4 degrees C. Fluorescence intensity of the
      fucose-labelled yeast forms was not increased over the hyphal-form cells. A germ
      tube-deficient mutant when exposed to hyphal-form growth conditions for 2 h
      showed much less binding of the fucose probe than the wild-type which produced
      germ tubes. Confirmation of specificity and the need for a carrier molecule was
      obtained by showing that Fuc-BSA (without fluorescein) effectively inhibited the
      binding of the fucose probe, although L-fucose itself was inactive, as was Gal
      BSA.

PMID- 9514577
TI  - All individual domains of staphylococcal protein A show Fab binding.
AB  - The interactions between the individual domains (E, D, A, B and C) of
      staphylococcal protein A (SPA) and Fc and Fab regions of human immunoglobulins
      were studied using real-time biospecific interaction analysis. An engineered
      domain Z, similar to fragment B but with a single glycine to alanine amino acid
      substitution, was also included in the study. The domains were expressed in
      Escherichia coli, affinity purified and immobilised onto sensor chip surfaces in
      a directed manner using a unique C-terminal cysteine residue engineered into the
      recombinant proteins. All domains bound to a recombinant human IgG1 Fc fragment
      with similar strength. For the first time, binding to human Fab was demonstrated
      for all native SPA domains, using both polyclonal F(ab')2 and a recombinant scFv
      fragment as reagents. Interestingly, the engineered Z domain showed a
      considerably lower affinity for Fab as compared to the native domains.

PMID- 9514578
TI  - Bactericidal activity of antibodies elicited against the Neisseria meningitidis
      37-kDa ferric binding protein (FbpA) with different adjuvants.
AB  - The 37-kDa ferric binding protein, FbpA, from three Neisseria meningitidis
      strains was purified to homogeneity with iron-affinity chromatography and used
      for immunisation of mice employing four different adjuvants: aluminium hydroxide,
      Freund's, the saponin Quil-A, and a Ribi adjuvant system (RAS). Controls
      immunised without adjuvant were also included. All sera obtained were
      monospecific for the meningococcal FbpA, with antibody titres higher when RAS and
      Quil-A were used (256), PBS resulting in titres similar to those of Freund's
      (64), and, surprisingly, with no antibodies elicited when aluminium hydroxide,
      the only approved adjuvant for use in humans, was used. All anti-FbpA sera bound
      to intact meningococcal cells, showing a complete cross-reactivity, but the
      bactericidal activity of anti-FbpA antibodies, demonstrated for the first time in
      this work, was low (32% of killing with the homologous strain), and the analysis
      of immunoglobulin isotypes showed that the non-bactericidal IgG1 was predominant.
      The results confirm that the FbpA is surface-exposed, antigenic, and able to
      elicit bactericidal antibodies, although, in the conditions and with the
      adjuvants tested, killing efficacy was low and cross-killing was very variable,
      not supporting the inclusion of this protein in vaccine formulations.
      Nevertheless, given the high conservation of the FbpA in the genus Neisseria, its
      surface exposure and its antigenicity, studies on immunisation with peptides
      corresponding to the exposed epitopes and/or new adjuvant systems could improve
      the bactericidal response to this protein, making it suitable for vaccine
      development.

PMID- 9514579
TI  - Serotonin transporter (5-HTT) gene polymorphisms are not associated with
      susceptibility to mood disorders.
AB  - In a population-based association study, we tested the hypothesis that allelic
      variants of the human serotonin transporter (5-HTT) gene confer susceptibility to
      mood disorders. Both a biallelic repeat polymorphism in the 5' promotor region
      that differentially modulates gene expression and a second intron variable-number
      tandem-repeat (VNTR) marker were genotyped in 294 controls and 115 patients with
      mood disorders. Subjects were of West European descent and included 36 patients
      with major depressive disorder (MDD) and 79 patients with bipolar I disorder
      (BD). No significant differences in genotype or allele frequencies were found at
      either locus between controls and combined patients, nor between controls and MDD
      or BD patients separately. Thus, our data do not support the association between
      depressive disorder and a nine-repeat allelic variant of the 5-HTT VNTR marker
      recently reported by Ogilvie et al. (Lancet 347:731-733, 1996). More importantly,
      no association between alleles conveying functional differences in 5-HTT gene
      expression and MDD or BD could be found. Taken together, our data suggest that
      the 5-HTT gene is not commonly involved in the susceptibility to mood disorders.

PMID- 9514580
TI  - Social adjustment in adult males affected with progressive muscular dystrophy.
AB  - Adult male patients affected with Becker (BMD, N = 22), limb girdle (LGMD, N =
      22) and facioscapulohumeral (FSHMD, N = 18) muscular dystrophy were interviewed
      to assess for the first time how the disease's severity and recurrence risk (RR)
      magnitude alter their social adjustment. BMD (X-linked recessive) is the severest
      form and confers an intermediate RR because all daughters will be carriers, LGMD
      (autosomal-recessive) is moderately severe with a low RR in the absence of
      consanguineous marriage, and FSHMD (autosomal-dominant) is clinically the mildest
      of these three forms of MD but with the highest RR, of 50%. Results of the
      semistructured questionnaire [WHO (1988): Psychiatric Disability Assessment
      Schedule] showed no significant difference between the three clinical groups, but
      more severely handicapped patients as well as patients belonging to lower
      socioeconomic levels from all clinical groups showed poorer social adjustment.
      Taken together, myopathic patients displayed intermediate social dysfunction
      compared to controls and schizophrenics studied by Jablensky [1988: WHO
      Psychiatric Disability Assessment Schedule]. Since the items of major dysfunction
      proportion among myopathic patients concern intimate relationships (70%),
      interest in working among those unemployed (67%), and social isolation (53%),
      emotional support and social and legal assistance should concentrate on these
      aspects. Interestingly, the results of this study also suggest that high RRs do
      not affect relationships to the opposite sex.

PMID- 9514581
TI  - Tryptophan hydroxylase genotype is associated with impulsive-aggression measures:
      a preliminary study.
AB  - To assess the relationship between two phenotypes in an extremely well
      characterized population of personality disorder patients-impulsive aggression
      and prolactin response to fenfluramine-and tryptophan hydroxylase (TPH) genotype,
      TPH genotype (at an intronic polymorphic site) and prolactin response to
      fenfluramine were assessed in 40 Caucasian patients with personality disorder.
      Impulsive aggression was assessed by using the Buss-Durkee Hostility Inventory
      (BDHI). Twenty-one male patients with the "LL" genotype had higher BDHI scores
      than men with the "UL" or the "UU" genotype. No relationship between genotype and
      prolactin response to fenfluramine was found. It was concluded that impulsive
      aggressive behavior in male personality disorder patients may be associated with
      the TPH genotype.

PMID- 9514582
TI  - Adenosine A1 receptor and bipolar affective disorder: systematic screening of the
      gene and association studies.
AB  - In the present study we sought to identify genetic variation in the adenosine A1
      receptor (A1AR) gene on chromosome 1q31-32.1, which through alteration of protein
      function or level of expression might contribute to the genetic predisposition to
      bipolar affective disorder. We performed a systematic mutation scan of the whole
      coding sequence as well as 5' and 3' untranslated regions by means of single
      strand conformation analysis. The region upstream to the coding sequence we
      investigated contains two functional promoters. Screening 42 patients with
      bipolar affective disorder, we detected 11 DNA sequence variants (48T/A, 267 +
      275C/T, 805T/G, 1777C/A, 1827C/T, 1904C/T, 2126G/T, 2294insT, 2776C/T, 2777del36,
      2819T/G). Determining the frequency of these variants in 42 anonymous blood
      donors, we observed a non-significant (P < 0.06) trend towards an
      underrepresentation of the 2126T variant in patients when compared to controls.
      On the other hand, the 2777del36 and the 2819G variant were not found among the
      controls. These findings were followed up in a large independent replication
      sample. However, we were not able to confirm the initial findings in the second
      sample. Our data suggest that genetically determined variation of the A1AR and
      its two promoters do not play a major role in the development of bipolar
      affective disorder.

PMID- 9514584
TI  - Obstetric complications and familial morbid risk of psychiatric disorders.
AB  - Obstetric complications (OCs) have been found to occur in higher frequency in
      patients with schizophrenia. One explanation for this finding is that the genes
      that contribute to the schizophrenia phenotype also influence the likelihood to
      experience OCs. If this were true, morbid risk of psychiatric illness should be
      higher in the first-degree relatives of both schizophrenic and control probands
      exposed to OCs, compared to probands not exposed to OCs. We set out to test this
      hypothesis. Information on OCs, blind to family history of psychiatric disorder,
      was collected retrospectively through maternal interview in 151 psychotic
      patients and 100 controls. Family history (FH) in relatives of cases (n = 600)
      and controls (n = 461) was assessed with the FH-RDC and through personal
      interviews. Tests for associations between family history and OCs were conducted
      using Cox proportional hazard regression. In the cases, familial morbid risk of
      affective disorder was greater in those with a history of OCs (hazard ratio (HR)
      = 1.9, P = 0.007). Analyses examining individual complications revealed
      associations between FH of affective disorder and pre-eclampsia (HR = 2.9, P =
      0.003) and FH of affective disorder and breech presentation (HR = 2.8, P = 0.02),
      especially when family history in the relatives was confined to affective illness
      in the mother (HR pre-eclampsia = 4.4, P = 0.009; HR breech-presentation = 4.2, P
      = 0.008). In controls, affective illness in the mother was not only associated
      with breech presentation (HR = 7.0, P = 0.01) and pre-eclampsia (HR = 4.4, P =
      0.03) but also with other complications. Familial morbid risk of schizophrenia
      and related psychoses was not associated with OCs. The positive associations
      between OCs and familial morbid risk of affective disorder suggest that the
      factors that contribute to familial aggregation of affective symptoms in
      psychotic patients also influence the likelihood to experience OCs. Although the
      proportion of OCs that could be attributed to these factors was very small, part
      of the relationship between family history of affective disorder and psychosis
      may be mediated by OCs.

PMID- 9514585
TI  - Serotonin transporter (5-HTT) gene and bipolar affective disorder.
AB  - Interactions with antidepressants, as well as other biochemical evidence,
      implicate the serotonin transporter 5-HTT in the etiology of affective disorders.
      However, genetic studies have produced conflicting results concerning an
      association of 5-HTT with bipolar disorder. We examined a variable number tandem
      repeat in the regulatory region of this gene to investigate the possible
      contribution of 5-HTT to bipolar disorder susceptibility in a 22-pedigree series.
      By affected-sib-pair analysis and the transmission/disequilibrium test, we found
      no significant linkage or association of 5-HTT to bipolar disorder. During the
      course of this study, we adapted a PCR technique designed to amplify long
      templates to replicating long GC stretches with complex structure. We also
      refined the location of 5-HTT by radiation hybrid mapping, placing the locus
      between D17S1294 and SHGC11022 on 17q11.2.

PMID- 9514583
TI  - European Multicentre Association Study of Schizophrenia: a study of the DRD2
      Ser311Cys and DRD3 Ser9Gly polymorphisms.
AB  - As part of the European Multicentre Association Study of Schizophrenia (EMASS),
      we studied polymorphisms in the dopamine DRD2 and DRD3 receptor genes. The EMASS
      collaboration was established to create a large, statistically powerful sample of
      schizophrenic patients and controls from different European centres. Previous
      studies have suggested associations between schizophrenia and the Ser311Cys
      polymorphism in exon 7 of the dopamine DRD2 receptor gene [Arinami et al.,
      (1994): Lancet 343:703-704] and a polymorphism Ser9gly in exon 1 of the dopamine
      DRD3 receptor gene [Crocq et al. (1992): J Med Genet 29:858-860]. We tested for
      these associations in samples of 373 and 413, and 311 and 306 patients and
      controls, respectively. We found no evidence for allelic association between
      schizophrenia and the Cys311 variant of the DRD2 receptor gene and no homozygotes
      for this variant were observed by any group. However, an excess of homozygotes
      for both alleles of the DRD3 polymorphism was observed in schizophrenic patients
      (chi2 = 8.54, P = 0.003, odds ratio = 1.64, 95% CI = 1.18-2.29). We also observed
      a significant excess of the 1-1 (Ser9Ser) genotype (chi2 = 8.13, P = 0.004, odds
      ratio = 1.7, 95% CI = 1.18-2.4). No evidence of heterogeneity between samples was
      detected and there was no evidence of an allelic association. These findings
      suggest that the rare Cys311 variant in exon 7 of the DRD2 receptor gene does not
      play a role in the pathogenesis of schizophrenia in European populations.
      Currently, our results do support the previous findings of an association between
      increased homozygosity of the Ser/Gly variant of the Dopamine D3 receptor gene
      and schizophrenia.

PMID- 9514586
TI  - Chromosome 22q11.2 interstitial deletions among childhood-onset schizophrenics
      and "multidimensionally impaired".
AB  - Since its first description almost a century ago schizophrenia with childhood
      onset, a rare yet devastating disorder, has been diagnosed in children as young
      as age 5. Recently, the velocardiofacial syndrome, whose underlying cause is
      interstitial deletions of 22q11.2, was found in 2 of 100 cases of schizophrenics
      with adult onset [Karayiorgou et al., Proc Natl Acad Sci USA 92: 7612-7616,
      1995]. No study has documented the prevalence of velocardiofacial syndrome and
      the 22q11.2 deletion in a population of schizophrenics with childhood onset. Here
      we describe the result of such a study in a sample originally selected for a
      trial of atypical antipsychotic drugs. A separate group of patients was also
      included in the study; they can best be accounted for as a variant of childhood
      onset schizophrenia (COS) and had been provisionally termed "multidimensionally
      impaired." Fluorescent in situ hybridization screening of 32 COS and 21
      multidimensionally impaired patients revealed 1 COS patient with an interstitial
      deletion spanning at least 2.5 megabases.

PMID- 9514587
TI  - Human novelty-seeking personality traits and dopamine D4 receptor polymorphisms:
      a twin and genetic association study.
AB  - Although it is well-established that genetic variation is important in causing
      individual differences in many human personality traits or based on family, twin,
      and adoption studies, the first reports that specific genetic polymorphisms might
      influence a normal dimension of personality were only recently published.
      Specifically, two studies have described significant associations between a
      dopamine D4 receptor (D4DR) exon III 48-base pair (bp) insertion/deletion
      polymorphism and the personality traits of novelty-seeking and positive emotional
      experience [Benjamin et al. (1996): Nat Genet 12: 81-84; Ebstein et al. (1996):
      Nat Genet 12:78-80]. The present study was undertaken to attempt to replicate
      these important and heuristic initial findings. Personality questionnaires
      measuring novelty-seeking and positive emotional experience were administered to
      306 male and female young adult twins (monozygotic 92 pairs, dizygotic 61 pairs)
      from the general population, 281 of whom were genotyped for D4DR exon I and III
      polymorphisms. No significant associations were observed between novelty-seeking
      or positive emotional experience and these D4DR polymorphisms. This failure to
      replicate the initial reports seems unlikely to represent measurement or genetic
      differences across studies, although environmental differences may be possible.
      Adequate statistical power in the present study suggests that these results are
      unlikely to be statistical "false negatives" and instead may reduce confidence in
      the generality of the initial positive findings.

PMID- 9514588
TI  - Alzheimer diseases: a model of gene mutations and susceptibility polymorphisms
      for complex psychiatric diseases.

PMID- 9514589
TI  - Analysis and meta-analysis of two serotonin transporter gene polymorphisms in
      bipolar and unipolar affective disorders.
AB  - The serotonin transporter is a compelling candidate gene to examine in bipolar
      and unipolar affective disorder, since drugs that specifically inhibit the
      serotonin transporter can successfully treat depression. Previous association
      studies of a VNTR polymorphism in intron 2 and a functional insertion/deletion
      polymorphism in the promoter of this gene have produced conflicting results. The
      present study examined allele and genotype frequencies for both of these
      polymorphisms and resulting haplotypes in 87 English Caucasian bipolar patients,
      125 English Caucasian unipolar affective disorder patients, and 174 controls. No
      significant associations were detected when these unipolar or bipolar cases were
      compared either separately or as a pooled "affective disorder" group to the
      controls. A meta-analysis of over 1,400 individuals of European Caucasian origin
      was then performed, comprising 772 controls, 375 bipolar and 299 unipolar
      patients for the VNTR polymorphism, and 739 controls, 392 bipolar and 275
      unipolar patients for the promoter polymorphism. A significant association of
      promoter allele 2 was shown with bipolar (estimated odds ratio 1.21; 95%
      confidence interval 1.00-1.45), unipolar (OR 1.23; 95% CI 1.01-1.42), and
      combined bipolar + unipolar groups (OR 1.22; 95% CI 1.04-1.42). There was no
      demonstrable allelic association of the VNTR polymorphism with affective
      disorder: for the combined bipolar + unipolar group the odds ratios for VNTR
      alleles 9 and 10, compared with the common allele 12 were 1.05 (95% CI 0.56-1.95)
      and 0.90 (95% CI 0.77-1.05). These results suggest that the promoter allele 2,
      which has previously been shown to result in lower levels of serotonin
      transporter transcription, may be associated with affective disorder risk.

PMID- 9514590
TI  - XYY chromosome anomaly and schizophrenia.
AB  - Sex chromosome anomalies have been associated with psychoses, and most of the
      evidence is linked to the presence of an additional X chromosome. We report a
      patient with XYY chromosome anomaly who developed schizophrenia.

PMID- 9514591
TI  - Exact elods and exact power for affected sib pairs analyzed for linkage under
      simple right and wrong models.
AB  - In the struggle to understand the inheritance of complex psychiatric diseases,
      investigators frequently turn to affected sib pair (ASP) methods of linkage
      analysis. This paper examines the quantity of "information" (as indicated by the
      expected maximum lod score [ELOD] and/or power), when ASP data originating from
      simple dominant or recessive inheritance are analyzed for linkage, both as simple
      dominant and as simple recessive. That is, these data are analyzed under both
      right and wrong models. Results are exact (i.e., not based on asymptotic
      approximations) and thus hold for small sample sizes (e.g., n = 20 sib pairs), as
      well as for large samples. It is shown that analyzing dominant ASPs (that is, sib
      pairs suffering from a dominantly inherited disease) as recessive (i.e., under
      the wrong model) can reduce the ELOD by 20-24% when recombination fraction
      (theta) is small. In situations where theta is large or gene frequency high, the
      information loss is less, because in those situations dominant ASPs contain very
      little information to begin with. For recessive ASPs, the information loss when
      analyzed under the wrong model is even more pronounced. The fact that a decision
      to sample ASP data discards more potential linkage information for dominant
      diseases than for recessive ones is also discussed, as are implications for more
      complex models. These findings are also of interest because it has been shown
      that the nonparametric Mean Test of ASPs is statistically identical to recessive
      lod score analysis [Knapp et al., Hum Hered 44:44-51, 1994]. Hence, the power
      results for the recessive analyses are also valid for the Mean Test, and thus are
      valuable for comparing how dominant and recessive ASP data fare in this
      particular nonparametric analysis.

PMID- 9514592
TI  - Association between the GABA(A) receptor alpha5 subunit gene locus (GABRA5) and
      bipolar affective disorder.
AB  - Genetic factors seem to play an important role in the pathogenesis of affective
      disorder. The candidate gene strategies are being used, among others, to identify
      the genes conferring vulnerability to the disease. The genes coding for the
      receptors of gamma-aminobutyric acid (GABA) have been proposed as candidates for
      affective disorder, since the GABA neurotransmitter system has been implicated in
      the pathogenesis of the illness. We examined the possible genetic association
      between the GABA(A) receptor alpha5 subunit gene locus (GABRA5) on chromosome 15
      and affective disorder, in 48 bipolar patients (BP), 40 unipolar patients (UP),
      and 50 healthy individuals, age- and sex-matched to the patients. All patients
      and controls were unrelated Greeks. Diagnoses were made after direct interviews
      according to the DSM-IV and ICD-10 criteria. For the genotyping, a dinucleotide
      (CA) repeat marker was used. The polymerase chain reaction (PCR) products found
      were nine alleles with lengths between 272 and 290 base pairs (bp). The
      distribution of allelic frequencies of the GABRA5 locus differed significantly
      between BP patients and controls with the 282-bp allele found to be associated
      with BP affective disorder, while no such difference was observed between the
      groups of UP patients and controls nor between the two patient groups. The
      presence or absence of the 282-bp allele in the genotype of BP patients was not
      shown to influence the age of onset and the overall clinical severity, but was
      found to be associated with a preponderance of manic over depressive episodes in
      the course of the illness.

PMID- 9514593
TI  - Bipolar affective disorder partially cosegregates with a balanced
      t(9;11)(p24;q23.1) chromosomal translocation in a small pedigree.
AB  - Analysis of an extended pedigree in which a balanced t(9;11)(p24;q23.1)
      translocation was found to cosegregate with bipolar affective disorder revealed
      that five of 11 translocation carriers had bipolar affective disorder and one
      carrier had unipolar depression. There were no affected individuals in the
      pedigree without the balanced translocation. We hypothesized that gene(s) or gene
      regulatory regions disrupted by the translocation might be contributing to the
      bipolar affective disorder in a dominant fashion. To test this hypothesis, we
      isolated the derivative chromosome 9 and derivative chromosome 11 in somatic cell
      hybrids and identified the nearest flanking markers on chromosome 9 (D9S230 and
      D9S2011E/HRFX3) and chromosome 11 (EST00652 and CRYA2). YAC contigs were
      constructed in the region of flanking markers for both chromosomes 9 and 11.
      Chromosome 11 breakpoint was localized within an 8-kb region in a small insert
      (100 kb) YAC. Chromosome 9 breakpoint was localized within approximately 2 Mb
      region. Several genes and ESTs including EST00652, CRYA2, DRD2, 5HTR3 on
      chromosome 11 and VLDLR and SLC1A1 on chromosome 9 were mapped within the
      vicinity of the breakpoint but were shown not to be disrupted by the
      translocation breakpoint. Although several possibilities exist regarding the role
      of the balanced translocation in developing bipolar affective disorder in this
      pedigree, including a chance cosegregation, identification of a disrupted gene or
      gene regulatory region with the help of physical mapping resources described in
      this study may help to identify the presence of a susceptibility gene for this
      disorder.

PMID- 9514594
TI  - Multiple threshold model for the onset of Alzheimer's disease in the NAS-NRC twin
      panel.
AB  - The three common alleles at the APOE locus influence the onset and lifetime risk
      of typical late-onset Alzheimer's disease (AD). Other loci may also alter risk of
      late-onset AD. One may assess the relative influence of APOE on the genetic
      contribution to AD by estimating the proportion of AD heritability that is
      explained by APOE polymorphism. To do this requires an initial estimate of the
      heritability of AD. Traditional methods are not appropriate for this estimation
      since they do not consider right-censoring (incomplete expression of the genotype
      owing to death) nor do they model the relation of onset age and disease
      liability. Here we present an analytic model that addresses both of these issues.
      Genetic and environmental influences on AD are examined by assuming that onset of
      dementia in AD is a late event in an extended degenerative process where earlier
      onset reflects a more rapid course of neurodegeneration. The model is fitted to
      the occurrence of AD among 9,786 members of the National Academy of Sciences
      National Research Council Registry of aging veteran twins. When both additive
      genetic and common environmental effects are used in the model, they explain 37%
      and 35%, respectively, of the variation in AD onset. Given the limited numbers of
      AD cases now available, models containing only additive genetic or shared
      environmental effects (explaining 75% and 65% of individual differences in
      disease onset, respectively) cannot be rejected in favor of a model that retains
      both influences.

PMID- 9514596
TI  - Bipolar and antisocial disorders among relatives of ADHD children: parsing
      familial subtypes of illness.
AB  - Attention deficit hyperactivity disorder (ADHD) is a familial disorder that is
      highly comorbid with conduct disorder and sometimes co-occurs with bipolar
      disorder. This pattern of comorbidity is also seen among relatives of ADHD
      probands. A growing literature suggests that ADHD with antisocial comorbidity may
      be nosologically distinct from other forms of ADHD. A similar pattern has been
      observed for ADHD and bipolar disorder. Given these results, along with the
      observed comorbidity between conduct and bipolar disorders, we used data from our
      study of 140 ADHD and 120 control families to determine if conduct and bipolar
      disorders in ADHD boys should be considered alternative manifestations of the
      same familial disorder. The probands and their relatives were examined with DSM
      III-R structured diagnostic interviews and were assessed for cognitive,
      achievement, social, school, and family functioning. Our results provide fairly
      consistent support for the hypothesis that antisocial- and bipolar-ADHD subtypes
      are different manifestations of the same familial condition. As predicted by this
      hypothesis, there was a significant three-way association between variables
      assessing the family history of each disorder. Moreover, when families were
      stratified into bipolar, antisocial, and other types, few differences emerged
      between the bipolar and antisocial families.

PMID- 9514595
TI  - Initial results of a genome survey for novel Alzheimer's disease risk genes:
      association with a locus on the X chromosome.
AB  - As the initial step in a systematic genome survey, 16 simple sequence tandem
      repeat polymorphisms that span the X chromosome at an average spacing of 10 cM
      were examined for allelic associations with typical-onset Alzheimer's disease
      (AD). The efficiency of this survey was substantially enhanced by genotyping
      pools of genomic DNA from 50 autopsy-confirmed AD cases and 50 autopsied controls
      who were similar in sex ratio, race, and age at death. The frequency of the
      DXS1047 202-bp allele was twice as common among AD cases (0.45+/-S.E. 0.06) than
      controls (0.22+/-S.E. 0.05), a finding that was reproduced in an independent and
      geographically disparate sample. Consistent with Hardy-Weinberg equilibrium, the
      proportion of women with AD who carried the 202-bp allele, 73% was nearly double
      that observed for men with AD, 38%. However, the frequency of the 202-bp allele
      was similar for men and women and the presence of this allele did not affect the
      age at onset of dementia in either sex. Furthermore, the frequency of the DXS1047
      202-bp allele in AD cases and controls was unaffected by the APOE genotype,
      indicating that these two loci modulate AD risk independently. Finally, the
      frequency of the 202-bp allele among 50 autopsy-confirmed cases of Parkinson's
      disease (0.29+/-S.E. 0.06) was indistinguishable from the control value,
      reflecting relative specificity for this allelic association with AD.

PMID- 9514597
TI  - ApoE genotype is a risk factor in nonpresenilin early-onset Alzheimer's disease
      families.
AB  - The apolipoprotein E (ApoE) genotype is a significant risk factor and modulator
      of age of onset of Alzheimer's disease (AD). We analyzed the effect of the ApoE
      genotype in two distinct early-onset familial AD groups: families with a mutation
      in the presenilin-1 gene (PS-1) on chromosome 14, and families without a mutation
      detectable in the PS-1, presenilin-2 (PS-2), and the amyloid precursor protein
      (APP) gene (non-PS early-onset familial AD). The ApoE genotype is clearly shown
      not to modulate age of onset in families with a mutation in the PS-1 gene and
      families with no lesion detectable in either the presenilin or APP gene. The
      effects of a double dose of ApoE4 on age of onset were not assessed in the PS-1
      AD families due to the lack of any affected ApoE4 homozygotes in the sample set;
      this insufficiency will need to be assessed in further studies. There was no
      association between the ApoE4 allele and AD in the PS-1 families. Non-PS early
      onset AD families were shown to have a significantly higher frequency of ApoE4
      compared to controls and the PS-1 AD group. These observations are important and
      suggest that 1) other genetic and environmental factors modify the AD phenotype
      in PS-1 and non-PS early-onset families; and 2) the ApoE4 allele is a significant
      risk factor in the etiology of non-PS early-onset AD and will be a useful adjunct
      in the diagnosis of unaffected family members.

PMID- 9514598
TI  - Active oxygens generation by flavonoids.
AB  - The hydrogen peroxide (H2O2)-generating effects of 14 flavonoids were
      investigated. Seven out of 14 flavonoids tested were found to generate H2O2 in an
      acetate buffer of pH 7.4. The H2O2-generating abilities of flavonoids decrease in
      the order of myricetin > baicalein > quercetin > (-)-epicatechin > (+)-catechin >
      fisetin = 7,8-dihydroxy flavone. This ability was observed in flavonoids with
      either a pyrogallol or catechol structure, and the pyrogallol-type flavonoids
      generated more H2O2 than the catechol-types. The amount of H2O2 generated by
      myricetin (pyrogallol-type flavonoid) was proportional to its concentration and
      to the reaction time until about 4 h. In addition, H2O2 generation by myricetin
      was dependent on the amount of dissolved oxygen in the buffer, and it was
      inhibited by the addition of superoxide dismutase. These results suggest that the
      flavonoids generate H2O2 by donating a hydrogen from their pyrogallol or catechol
      structure to oxygen, through a superoxide anion radical. It was also found that
      flavonoids which generated more H2O2 were more powerful antioxidants in the NADPH
      dependent lipid peroxidation of rat microsomes.

PMID- 9514599
TI  - Effects of gonadal hormones on the zonal expression of rat hepatic phenol
      sulfotransferases.
AB  - Estradiol benzoate (EB) and testosterone propionate (TP) were administered to
      male and female Wistar rats, and their effects on the zonal expression of hepatic
      phenol sulfotransferase (P-ST) activities were determined at pH 5.5 and 7.4.
      Cytosolic fractions from periportal (PP) and perivenous (PV) hepatocytes were
      prepared by the dual-digitonin-pulse perfusion technique. In control rats, P-ST
      activities assayed at pH 5.5 and 7.4 were higher in males than in females, and
      were higher in the PV fraction than in the PP fraction in both sexes. P-ST
      activities were increased by the administration of TP in the PP and PV fractions
      of females, whereas the same treatment diminished the enzyme activities in both
      fractions of the males. EB administration gave reduced P-ST activity at pH 5.5 of
      both fractions, irrespective of sex, but not a marked difference at pH 7.4.
      Chromatofocusing of PP and PV fractions revealed the presence of P-ST isoforms
      eluted at approx. pH 8.0 (peak 1), 7.5 (peak 2), 7.0 (peak 3) and 6.0 (peak 4).
      In male rats, peak 3, which showed high enzyme activity at pH 5.5 in the PP and
      PV fractions, was markedly decreased by EB treatment, whereas in females, peak 3
      was present only in the PV fraction and was not affected by EB administration. TP
      treatment did not show remarkable changes in P-ST peaks in the males, while peaks
      2 and 3 were increased in the females. Immunoblot analysis revealed the presence
      of multiple P-ST isoforms which showed different immunoreactivity and
      electrochemical properties.

PMID- 9514600
TI  - Formation of hydroxyfuranone and hydroxypyranone derivatives with DNA-breaking
      activity in the Maillard reaction of glucose and albumin under physiological
      conditions.
AB  - Formation of DNA breaking hydroxyfuranone and hydroxypyranone derivatives in the
      Maillard reaction of glucose and bovine serum albumin (BSA) under physiological
      conditions was investigated. A mixture of glucose and BSA was incubated at 37
      degrees C in water or in 1 M phosphate buffer (pH 7.4). The ethyl acetate/2
      propanol extract of the reaction mixtures showed significant DNA breaking
      activity against supercoiled DNA especially in the presence of Fe(III) ion. Gas
      chromatography/mass spectrometry analysis of the mixture revealed the formation
      of DNA breaking hydroxyfuranones (HMF and DMHF) and hydroxypyranone (DDMP).

PMID- 9514601
TI  - Purification method for human plasma kallikrein by a new affinity chromatography.
AB  - We synthesized a new affinity gel (PKSI-Toyopearl) using a selective synthetic
      inhibitor of plasma kallikrein (PKSI-527) as an affinity ligand, and employed it
      for the rapid purification of plasma kallikrein from human plasma. Human plasma
      activated with kaolin after acid treatment was applied to a PKSI-Toyopearl
      column. Adsorbed protein was eluted with 50 mM glycine-hydrochloric acid buffer
      (pH 3.0). Plasma kallikrein was purified 181-fold with a yield of 85% from the
      kaolin-activated plasma. Further purification was performed by chromatography on
      a DEAE-Toyopearl 650M column. Plasma kallikrein was finally purified 1720-fold
      with a 63% yield by these procedures. On sodium dodecyl sulfate (SDS)
      polyacrylamide gel electrophoresis, a band was observed at approximately 88 kDa.
      These findings indicate that PKSI-Toyopearl is a valuable tool for the
      purification of plasma kallikrein from human plasma.

PMID- 9514602
TI  - Verapamil inhibits elastase release and superoxide anion production in human
      neutrophils.
AB  - In response to activation of phagocytic cells and during inflammatory disorders,
      some proteases and very reactive oxygen species are produced. These proteases and
      oxidants are involved in many diseases like tissue injury or atherosclerosis. We
      have shown in vitro that verapamil, a calcium channel blocker, had antielastase
      and antioxidant properties. This drug inhibited the release of elastase by
      neutrophils in a dose-dependent manner when these cells were stimulated by
      phorbol-myristate-acetate (PMA), by N-formyl-methionyl-leucylphenylalanine (fMLP)
      and by the calcium ionophore A23187 (Ca.I). In addition, verapamil inhibited
      superoxide anion when human neutrophils were stimulated by PMA, fMLP,
      dioctanoylglycerol (DiC8), Ca.I or by opsonised zymosan (OZ). Verapamil did not
      act by scavenging elastase or oxidants as demonstrated in cell-free models which
      showed no direct antielastase or antioxidant effect involved by verapamil.
      Superoxide anion and elastase inhibition by verapamil has been considered to the
      mobilization of cytosolic calcium and inhibition of protein kinase C. The results
      suggest that verapamil might contribute help the development and progression of
      atheroma where oxidants and elastase are involved.

PMID- 9514603
TI  - Comparative glucoregulatory responses of mice to restraint and footshock stress
      stimuli.
AB  - Effects of two types of stress, restraint and footshock, on plasma glucose level,
      insulin secretion, and glucose uptake by the liver, heart and femoral muscle were
      investigated in mice. Plasma glucose level gradually increased and reached
      maximum at 60 min after the onset of restraint stress, while footshock stress
      slightly increased plasma glucose level only 15 min after the onset of the
      stress, and this subsequently decreased significantly. The basal plasma insulin
      level and glucose-induced insulin secretion significantly decreased during both
      the stress stimuli. Glucose uptake by the femoral muscle was slightly increased
      during restraint stress, and was significantly increased during footshock stress.
      These results suggest that the transient increase in plasma glucose level during
      the early period of both stress stimuli might be caused by the inhibition of
      insulin secretion, and subsequent decrease in plasma glucose level during the
      latter phase of both stress stimuli was probably due to the increase in glucose
      uptake by the skeletal muscle. The present study confirmed that there was a
      difference in stress-induced glucoregulatory changes between restraint stress and
      footshock stress. This difference might be due to the degree of muscle movement
      during the stress stimuli.

PMID- 9514604
TI  - Effects of Hange-shashin-to on cholera toxin-induced fluid secretion in the small
      intestine of rats.
AB  - The effects of Hange-shashin-to (TJ-14) on cholera toxin-induced intestinal fluid
      secretion were studied to elucidate the mechanism by which this kampo medicine
      manifests antidiarrheal effects. TJ-14 suppressed the intestinal fluid secretion
      induced by cholera toxin (1 microg/rat) in a dose-dependent manner at doses
      between 125 and 1000 mg/kg. It also inhibited the luminal prostaglandin E2 (PGE2)
      level. On the other hand, serotonin (5-HT) release was not affected by TJ-14.
      Subcutaneous injection of indomethacin at 10 mg/kg or ondansetron at 100
      microg/kg significantly suppressed intestinal secretion. The luminal PGE2 level
      was also inhibited by indomethacin (10 mg/kg, s.c.). TJ-14, even at 10(-4) g/ml,
      had little effect on the phasic contraction of isolated guinea pig ileum induced
      by 5-HT (2 x 10(-6) g/ml), while ondansetron suppressed the phasic contraction
      caused by 5-HT. These results indicate that TJ-14 is useful in suppressing
      cholera toxin-stimulated intestinal fluid secretion, and that this effect is
      partially due to its suppressive action on the PGE2 level.

PMID- 9514605
TI  - Mechanism of the protective effect of sodium malate on cisplatin-induced toxicity
      in mice.
AB  - We examined the mechanism of the protective effect of sodium malate on cis
      diamminedichloroplatinum(II) (cisplatin, CDDP)-induced nephrotoxicity in mice and
      obtained the following findings: 1: Sodium malate showed a maximum reduction of
      toxicity when it was administered at the same time as CDDP or at 30 min before
      the administration of CDDP; the reduction was significantly decreased when sodium
      malate was given after the administration of CDDP. 2: It is thought that
      diamminoplatinum(II) malate (DPM) is produced in the body following the
      administration of a combination of CDDP and sodium malate. DPM showed the same
      antitumor effect as CDDP and produced little nephrotoxicity. 3: When CDDP was
      combined with sodium malate, the time necessary for the elimination of platinum
      from the blood was prolonged, showing a intermediate value between the times for
      the elimination of CDDP and DPM from the blood. When the drug clearance was
      calculated based on this result, it was found that about 40% of the CDDP
      administered is converted to DPM in the blood. 4: In an experiment using L-[14C]
      malic acid, it was shown that sodium malate is distributed in the liver and the
      kidney at high concentrations, but in the tumor at only a low concentration. 5:
      When sodium malate was administered in combination with CDDP, the amount of
      platinum which accumulated in the kidney after 24 h was decreased by about 55%
      compared with the uncombined group, but there was no change in the amount of
      platinum which accumulated in the tumor. These results suggest that the sodium
      malate administered may be distributed rapidly in the blood and the tissue, and
      about 40% is bound to CDDP and converted to DPM, thus reducing the nephrotoxicity
      of CDDP.

PMID- 9514606
TI  - Complement activation by diesel exhaust particles (DEP).
AB  - The effect of diesel exhaust particles (DEP) on the hemolytic activity of human
      serum complement was investigated. Previous treatment of human serum with DEP
      extracts at 37 degrees C decreased the hemolytic activity of human serum
      complement dose dependently, to 20% of its original value. This decrease in
      complement activity by DEP extracts was observed with previous incubation at 37
      degrees C but not at 4 degrees C. A decrease in complement activity was observed
      after previous incubation at 37 degrees C in the presence of EGTA/Mg but not in
      the presence of EDTA, indicating that the alternative pathway of the complement
      system had been activated by DEP extracts. Activation of the complement system by
      DEP extracts was further demonstrated by observation of the cleavage of the third
      component of the complement (C3) in serum to C3b with immunoelectrophoresis using
      goat anti-human C3 antiserum. This cleavage of C3 was similarly observed in the
      presence of EGTA/Mg, indicating the activation of the alternative pathway of the
      complement system by DEP extracts. These results indicate that DEP can activate
      the alternative pathway of the complement system, resulting in a decrease in the
      hemolytic activity of complement and in the production of biologically active
      degradation products of complement proteins such as C3a. The biological
      significance of the activation of the complement by DEP in the alveolus is
      discussed in relation to the influx of neutrophiles.

PMID- 9514607
TI  - Effects of preparations of Chinese medicinal prescriptions on digestive enzymes
      in vitro and in vivo.
AB  - The effects of preparations of Chinese medicinal prescriptions on the activities
      of digestive enzymes were investigated. The starch dextrinizing activity of
      pancreatin was inhibited by Keishi-bukuryo-gan, Sho-seiryu-to, Hachimi-jio-gan,
      Unsei-in and Keishi-ka-shakuyaku-to to below 40% of the control activity. Hachimi
      jio-gan and Sho-seiryu-to, in particular, lowered the activity to 4% and 24% of
      the control activity, respectively. The protein digestive activity of pancreatin
      was lowered by Keishi-bukuryo-gan, Oren-gedoku-to, Ryutan-shakan-to, Tokaku-joki
      to, Yokuinin-to and Hange-shashin-to, to 56 to 70% of the control activity. To
      investigate the effects of the preparations of Chinese medicinal prescriptions on
      digestive enzymes in vivo, 600 mg (185 kBq) of 125I-egg white albumin were
      administered orally to rats 30 min before the administration of 100 mg of Tokaku
      joki-to or Oren-gedoku-to. The radioactivity which transferred to the blood was
      less in the animals pre-fed these prescriptions than in the control animals,
      indicating that the digestion of egg white albumin was delayed in the presence of
      the prescriptions.

PMID- 9514608
TI  - Effects of Aconitum alkaloid kobusine and pseudokobusine derivatives on cutaneous
      blood flow in mice.
AB  - Aconitum alkaloids of the C20-diterpenoid type, kobusine (1) and pseudokobusine
      (2), and their acetyl, benzoyl, propionyl or cinnamoyl derivatives are examined
      for their peripheral vaso-activities by laser-flowmetrical measurement of the
      cutaneous blood flow in the hind foot of mice after intravenous administration. A
      dose-relationship of maximally increased blood flow after the administration of
      either of the Aconitum alkaloids existed. Kobusine 15-acetate (4), 11-benzoate
      (6) and 15-benzoate (7) were significantly effective at a low dose of 1 mg/kg,
      whereas the other kobusine derivatives were all inactive. Alkaloid 2, alone, and
      the 11-acetate (14), 15-acetate (15), 15-propionate (22) and 15-cinnamoate (25)
      were all active at 1 mg/kg and the effect of 14 at 5 mg/kg was remarkable. The
      activity of 2 was abolished by esterification of the hydroxyl group at C-6.
      Alkaloid 15 at 5 mg/kg showed a pattern of time course of blood flow in which the
      increase was rapidly replaced with a decrease below the basal flow, probably
      suggesting the effect of excessive doses. Conclusively, it is considered that the
      hydroxyl groups of alkaloids, especially a free OH group of 2 at C-6, are
      important for action on the peripheral vasculature leading to dilatation, and
      these results indicated that esterification of the hydroxyl group at C-15 with
      either acetate or benzoate may contribute to enhancement of the activity of the
      parent alkaloids.

PMID- 9514609
TI  - Intracellular disposition and cytotoxicity of transferrin-mitomycin C conjugate
      in HL60 cells as a receptor-mediated drug targeting system.
AB  - A macromolecular conjugate of mitomycin C (MMC) with transferrin (TF) which
      possessed binding ability for TF receptor was synthesized. The conjugate (TF-MMC)
      was internalized into the human leukemia cell line HL60 cells and distributed
      into intracellular fractions, then exocytosed into an incubation medium. Although
      these phenomena were similar to those of TF, part of the internalized TF-MMC was
      degraded to a trichloroacetic acid (TCA)-soluble fraction. Therefore, the
      intracellular disposition of the conjugate was analyzed kinetically. The mean
      time of internalization of TF-MMC (7.14 min) was longer than that of TF (5.46
      min). The mean exocytosis time of TF-MMC (22.1 min) was also longer than that of
      TF (13.0 min). Although elongation of both the internalization and exocytosis
      steps was responsible for the increase in recycling time of the conjugate, the
      binding process to the TF receptor in the internalization stage was found to be
      markedly retarded. The recycling times of TF-MMC and TF were 29.2 and 18.5 min,
      respectively. The mean decomposition time of TF-MMC was 76.3 min. Proliferation
      of HL60 cells was inhibited by TF-MMC in vitro. These results indicate that the
      TF-MMC was internalized via a TF receptor and a part of the internalized TF-MMC
      was degraded, so the released MMC might represent antitumor activity. TF-MMC was
      demonstrated to be a useful hybrid as a receptor-mediated targeting system.

PMID- 9514610
TI  - Eurycoma longifolia JACK and orientation activities in sexually experienced male
      rats.
AB  - The effects of Eurycoma longifolia JACK were studied on the orientation
      activities of sexually experienced male rats towards receptive females (mounting,
      licking, anogenital sniffing), environment (exploration, raring, climbing),
      themselves (genital grooming, non-genital grooming) and mobility (unrestricted,
      restricted) after dosing them with 200, 400 and 800 mg/kg body weight twice daily
      for 10 d prior to the test. The results showed that E. longifolia JACK modified
      the orientation activities of the treated male rats in that they significantly
      displayed more frequent and vigorous mounting, licking and anogenital sniffing
      towards the receptive females, and it further intensified self orientation as
      indicated by the increased grooming of the genitals compared to the controls
      (p<0.05). In addition, rats treated with 800 mg/kg of methanol, water and butanol
      extracts of E. longifolia JACK continued to show confinement to a particular area
      of the cage (around the female), thus showing restriction in movement as compared
      to the controls (p<0.05). However, the treated males possessed a lack of interest
      in the external environment as indicated by a reduction in exploration, raring
      and climbing on the cage wall. Hence, the present study further supports the folk
      use of E. longifolia JACK as an aphrodisiac.

PMID- 9514611
TI  - Urinary excretion of D-serine in human: comparison of different ages and species.
AB  - The urinary excretion of D-serine (D-Ser) in human, rat and dog of various ages
      was studied. Great amounts of D-Ser were consistently excreted in human urine
      throughout life. No age-dependent changes were observed in urinary D-Ser/total
      Ser ratios from the newborn to the aged. D-Ser/creatinine ratios in adult human
      urine were found to be relatively constant in individuals. The constant excretion
      of D-Ser in human urine was confirmed by analyzing the consecutive 24 h urine of
      three volunteers. High concentrations of D-Ser and D-alanine (D-Ala) were found
      in adult dog urine. The urinary D-Ser concentration was high in young rats at
      unweaned and weaned periods, and then declined with increasing age. In contrast,
      the urinary D-Ala concentration was very low in suckling rats, and increased
      rapidly after the weaned state and then declined with increasing age. The species
      and age-related excretion of D-Ser in mammalian urine is considered to be due to
      the differences in the renal handing of D-Ser, because plasma D-Ser
      concentrations among the groups were not so different. Although free D-Ser has
      been detected in animal foods and human colostrum, the amount is insufficient to
      explain the concentration of D-Ser found in urine. These results indicate that
      urinary D-Ser in mammals may be mainly of endogenous origin.

PMID- 9514612
TI  - The involvement of Ca2+-dependent protein kinase in the regeneration of rice
      cultured suspension cells.
AB  - Short-term cultured cells of rice (Oryza sativa) were found to be capable of
      regeneration, in contrast to those obtained from long-term cultures. For
      clarification of the mechanism of regeneration, it was first necessary to
      distinguish protein kinase activity in long-term and short-term cultured cells;
      this activity was found greater in the former than latter. The activity was
      dependent on calcium, not phospholipid, phorbol ester or calmodulin. The apparent
      Mr of both Ca2+-dependent protein kinases was 32 kDa according to gel
      phosphorylation. Phosphoserine was identified in serine residues in
      phosphorylated histone III-S by phosphoamino acid analysis. A Ca2+-dependent
      protein kinase having a relative Mr of 32 kDa is thus shown to be possibly
      essential to regeneration in rice cultured cells.

PMID- 9514613
TI  - Gene expression of the two heavy chains and one light chain forming the inter
      alpha-trypsin-inhibitor in human tissues.
AB  - Human inter-alpha-trypsin-inhibitor (ITI) is a serine proteinase inhibitor with a
      molecular weight of 220 kDa which consists of 3 different polypeptides. The
      constitutive components are 2 heavy chains (H1 and H2 chains) and 1 light chain
      (L chain), and its inhibitory activity is considered to be derived from this L
      chain. It has also been reported that this L chain is almost identical to the
      trypsin inhibitor (UTI) occurring in human urine. We examined the gene expression
      of the ITI constitutive peptides in human tissues using the reverse transcription
      (RT) -PCR technique. As a result, the genes of the H1 chain were found to be
      expressed in various tissues, particularly strongly in the liver. On the other
      hand, the genes of the H2 chain were found to be strongly expressed in the
      adrenal glands, brain, kidneys, and lungs, as well as the liver. Further, the PCR
      amplification product of the L chain was strongly detected not only in the liver
      but also in the pancreas, kidneys, lungs, stomach and testes. These results
      suggest the possibility that the major tissue which produces ITI is the liver,
      and the H chains and L chain (UTI) are produced as a component of ITI- related
      proteins in other tissues as well as in the liver.

PMID- 9514614
TI  - Two genes involved in the 1,3-diaminopropane production pathway in Haemophilus
      influenzae.
AB  - We previously cloned and sequenced the Acinetobacter baumannii dat and ddc genes
      encoding L-2,4-diaminobutyrate: 2-ketoglutarate 4-aminotransferase (DABA AT) and
      DABA decarboxylase, respectively, involved in the 1,3-diaminopropane (DAP)
      production pathway. Homology searches of the gene products provided an indication
      that a similar gene cluster is present in the genome of Haemophilus influenzae
      Rd. This was first verified by detection of the corresponding enzyme activities
      in and the production of DAP by all H. influenzae strains examined. Both of the
      crude enzymes from the representative strain of H. influenzae showed catalytic
      properties essentially similar to the A. baumannii DABA AT and DABA DC. An
      Escherichia coli clone carrying the dat homolog of H. influenzae Rd showed a high
      level of DABA AT activity, the enzyme protein responsible being detected by
      immunoblot analysis. These results specify the two H. influenzae genes involved
      in DAP production.

PMID- 9514615
TI  - Effects of fatty acids on serum binding between furosemide and valproic acid.
AB  - The effects of fatty acids, including oleate, on the interaction between
      furosemide and valproic acid in sera at respective serum therapeutic
      concentration levels were investigated using an ultrafiltration technique. The
      free fraction of furosemide was significantly increased in the presence of
      valproic acid. Mutual displacement experiments indicated that furosemide and
      valproic acid share a common high affinity binding site on human serum albumin
      (HSA). The serum free fraction of furosemide was increased by the presence of six
      or more fatty acid molecules per HSA molecule. This fatty acid-induced increase
      in the unbound fraction of furosemide was further increased by the binding of
      valproic acid. However, the inhibition of furosemide binding to serum for a fatty
      acid-valproic acid-furosemide system is nearly the same as the additive effect of
      fatty acid and valproic acid on the furosemide to serum. Thus, the mechanism for
      the displacement of HSA-bound furosemide by valproic acid was concluded to be
      different from that for fatty acid-catalyzed displacement.

PMID- 9514616
TI  - Protein C activation by recombinant thrombomodulin in plasma.
AB  - Recombinant glycosaminoglycan-modified urinary thrombomodulin (GAG-UTM), which
      partially improved the amino acid sequence of human urinary thrombomodulin (UTM),
      was expressed in C127 cells. GAG-UTM accelerates protein C activation by thrombin
      and also thrombin inhibition by antithrombin III (ATIII) in the buffer system.
      Both accelerating activities of GAG-UTM are more potent than those of unmodified
      recombinant UTM (r-UTM) without a GAG chain. As ATIII in plasma also inhibits
      protein C activation by a thrombin-thrombomodulin complex, we studied whether GAG
      UTM accelerates protein C activation in plasma. GAG-UTM suppressed the generation
      of thrombin in activating plasma protein C stronger than r-UTM. By Western blot
      analysis using anti-protein C antibody, activated protein C was generated by GAG
      UTM more than by r-UTM. From these results, the acceleration of activated protein
      C formation by GAG-UTM was confirmed in plasma too.

PMID- 9514617
TI  - Inhibitory effects of pentamethine trinuclear cyanine dyes on ADP/Fe2+-induced
      lipid peroxidation in rat liver mitochondria: changes in the mode of action with
      the hydrophobic nature of the dyes.
AB  - The effects of various pentamethine trinuclear cyanine dyes, each of which has
      three alkyl chains, on ADP/Fe2+-induced lipid peroxidation in rat liver
      mitochondria were examined. Although the dye having the shortest -C2H5 chains
      (tri-S-C2(5)) did not show any appreciable effect, the dyes having -C4H9 (tri-S
      C4(5)), -C7H15 (tri-S-C7(5)), and -C12H25 (tri-S-C12(5)) chains significantly
      inhibited lipid peroxidation, the most potent inhibitory effect being observed
      with tri-S-C7(5). The mode of antiperoxidation effect of the dyes was dependent
      on the length of the alkyl chains. The relatively hydrophilic dye tri-S-C4(5) was
      suggested to scavenge radicals more efficiently at or near the membrane surface
      rather than in the interior of the lipid membrane, whereas the more hydrophobic
      dye tri-S-C7(5) was suggested to scavenge radicals efficiently in the membrane
      rather than at or near the membrane surface. The hydrophilic/hydrophobic balance
      of the dye was found to regulate the site of action of the dyes.

PMID- 9514618
TI  - Cholesterol-lowering effects of psyllium seed associated with urea metabolism.
AB  - Twenty-eight mild hypercholesterolemic male and female adults were orally
      administered psyllium seed for 3 months. After psyllium treatment, the serum
      total cholesterol, low-density-lipoprotein-cholesterol and atherogenic index
      significantly decreased, but levels of high-density-lipoprotein-cholesterol,
      triglyceride and urea nitrogen did not. To determine the parameters associated
      with the cholesterol-lowering effect in the subjects' backgrounds, both
      biochemical and hematological parameters, we statistically examined the
      correlation between pretreatment parameters and the absolute change of total
      cholesterol level. The absolute change of total cholesterol level showed a direct
      correlation with the triglyceride level at pretreatment (r=0.41, P=0.03) and had
      an inverse correlation with urea nitrogen level (r=-0.46, P=0.01) but not with
      the total cholesterol level (r=-0.18). The change in urea nitrogen level had an
      inverse correlation with the urea nitrogen level itself at pretreatment (r=-0.82,
      P=7 x 10[-8]) and had a direct correlation with the triglyceride level (r=0.43,
      P=0.02). The change in triglyceride level had an inverse correlation with the
      urea nitrogen level (r=-0.48, P=0.008). Furthermore, the change in total
      cholesterol level had direct correlations with changes in the triglyceride level
      (r=0.56, P=0.002) and the urea nitrogen level (r=0.51, P=0.006), but these
      changes in triglyceride and urea nitrogen level did not correlate significantly.
      These findings suggest the close association of urea nitrogen and lipid
      metabolism in hyperlipidemia and psyllium seed treatment.

PMID- 9514619
TI  - Intravitreous delivery of dexamethasone sodium m-sulfobenzoate from poly(DL
      lactic acid) implants.
AB  - Biodegradable intravitreal rod-shaped implants containing dexamethasone sodium m
      sulfobenzoate (DMSB) were prepared from blends of poly(DL-lactic acid) (PLA) with
      number-average molecular weight 2000 (PLA2000) and 4000 (PLA4000). The effect of
      the fraction of PLA2000 on the release of DMSB from the implant was investigated
      after implantation in the vitreous body of rabbit eyes. After the initial burst,
      the drug was released slowly from the blended PLA implants with a PLA2000
      fraction of below 30 wt% in normal eyes within a period of 28 d. For the implants
      with a higher PLA2000 fraction of over 50 wt%, the drug was released following
      approximately first order kinetics. In the vitrectomized eyes, the release of
      DMSB from the PLA2000/PLA4000 (5/5) implant was 2.5 times more rapid than in
      normal eyes, and the clearance of drug was also appreciably accelerated as
      compared with that in normal eyes.

PMID- 9514620
TI  - Expression in Pseudomonas aeruginosa of an erythromycin-resistance determinant
      that encodes the mphA gene for macrolide 2'-phosphotransferase I from Escherichia
      coli.
AB  - We studied the expression in Pseudomonas aeruginosa of an erythromycin-resistance
      (EMr) determinant that included the mphA gene for macrolide 2'-phosphotransferase
      I and originated in Escherichia coli. A recombinant plasmid, pTZ3609, that
      consisted of the EMr determinant and a broad-host-range vector RSF1010, endowed
      P. aeruginosa with high-level resistance to erythromycin. Furthermore, the EMr
      determinant on a self-transferable plasmid, RP1, was transferred from E. coli to
      P. aeruginosa by conjugation.

PMID- 9514621
TI  - Lipo-microdialysis: a new microdialysis method for studying the pharmacokinetics
      of lipophilic substances.
AB  - A new microdialysis method (Lipo-MD) using a lipid emulsion as the perfusate
      instead of Ringer's solution as in conventional microdialysis (MD) was designed.
      Recovery profiles of the alkylparabens (APBs) dissolved in Ringer' s solution by
      Lipo-MD were compared with those by MD in vitro. Recovery of APBs in the
      perfusate in MD decreased with the increasing lipophilicity of APBs, whereas that
      in Lipo-MD increased. The enhancement of the relative recovery of APBs by Lipo-MD
      to MD for methyl-, ethyl-, propyl-, and butylparaben were 2.03, 5.24, 77.0, and
      390.7, respectively. The utility of Lipo-MD for determination of lipophilic
      substances to perform pharmacokinetic study was suggested.

PMID- 9514622
TI  - Articles in Blood Cells, Molecules, & Diseases Are Posted on the World Wide Web
      Every Two Weeks. The Current Issue Is Not Complete. Please See the Abstract for
      More Information.
AB  - Blood Cells, Molecules, & Diseases is an electronically published journal with an
      average accept-to-publish time of 7 days. The journal emphasizes not only blood
      cells, but also covers the molecular basis of hematologic disease and studies of
      the diseases themselves. Research areas include: Hematologically important
      mutations Bone marrow Genetics Leukemia Molecular biology of blood Biochemistry
      of blood The articles are published on the World Wide Web at
      www.seconde.scripps.edu, where more recent articles may be available. Printed
      issues are created every 16 weeks and cover 8 on-line issues. For more
      information, please visit the home page at www.apnet.com.

PMID- 9514623
TI  - In vivo preclinical test models for studying airway mucus secretion.
AB  - There are many in vivo animal models for studying airway mucus secretion and
      hypersecretion, each with advantages and disadvantages. Use of a particular test
      system will depend upon the aspect of secretion to be modelled. Airway
      hypersecretory diseases exhibit chronic mucus hypersecretion, of which the
      clinical impact is predominantly in the distal airways. The majority of
      documented test preparations study acute secretion, invariably using tracheal
      preparations, but have been invaluable in elucidating the normal physiology of
      airway mucus secretion. Chronic models of the hypersecretory state in the distal
      airways have been developed, but are predominantly histologic in nature (for
      example quantification of increased goblet cell number). There are few
      investigations of mucus hypersecretion. Examination of the 'antisecretory'
      potential of pharmaceutical compounds has been investigated predominantly in
      chronic histologic models with the drug being given 'prophylactically' rather
      than 'therapeutically'. Refinement of chronic hypersecretory models should lead
      to elucidation of the connection between airway irritation, inflammation, MUC
      gene expression, mucous cell hyperplasia/metaplasia, airway hypersecretion and
      bronchial hypersecretory disease.

PMID- 9514624
TI  - The use of bronchodilators in stable chronic obstructive pulmonary disease.

PMID- 9514625
TI  - In vitro models for airways mucin secretion.

PMID- 9514626
TI  - PAF-induced secretory hyperresponsiveness in the ferret trachea to bradykinin and
      its pharmacological inhibition.
AB  - Both PAF (10 microM) and bradykinin (0.1-10 microM) increased lysozyme (from
      submucosal gland serous cells (+138 and +45% for PAF, 10 microM, and bradykinin,
      1 microM, respectively) and albumin (mainly active epithelial transport; +387 and
      +108%) outputs into the ferret tracheal lumen in vitro and reduced the negativity
      of the potential difference (PD: -33 and -17%) across the trachea. Since PAF can
      cause bronchial smooth muscle hyperresponsiveness, we tested whether these
      effects were interactive, and if PAF would increase the actions of bradykinin.
      The bradykinin-induced lysozyme and albumin outputs were more than trebled and
      the PD change was enhanced by PAF, after the immediate secretory effects of the
      latter had returned to baseline. The secretory and PD responses to PAF were all
      prevented by the PAF-antagonist WEB 2086 and by a combination of the free-radical
      scavengers catalase and SOD, indicating that PAF may act on specific receptors to
      release free-radicals. Nedocromil sodium inhibited the increase in lysozyme and
      albumin outputs produced by PAF, but had no effect on the PD response. None of
      the tracheal responses to bradykinin was modified by WEB 2086, catalase and SOD,
      or nedocromil sodium. The secretory and PD hyperresponsiveness to bradykinin
      caused by PAF was prevented by WEB 2086 and by catalase and SOD. Nedocromil
      sodium greatly inhibited the lysozyme and albumin hyperresponsiveness but had no
      effect on the PD response. Thus PAF may release more than one type of radical
      which have differential effects on serous cells and albumin transport compared
      with PD; nedocromil sodium may act only against the radical causing the secretory
      effects.

PMID- 9514629
TI  - Volume contents and index
AB  - No abstract Copyright 1997 The International Association of Biological
      Standardization.

PMID- 9514631
TI  - Call for Papers: European Perspectives on Young Offenders: Research into Practice
AB  - No abstractCopyright 1997The Association for Professionals in Services for
      Adolescents.

PMID- 9514627
TI  - The effects of ML 3000 on antigen-induced responses in sheep.
AB  - ML 3000 is a dual inhibitor of cyclooxygenase (COX) and 5-lipoxygenase (5-LO),
      two enzymes that contribute to the airway inflammation in asthma. When
      administered as an aerosol at a dose of 100 mg, 0.5 h before antigen challenge in
      allergic sheep, ML 3000 provided significant inhibition against the early
      bronchial response (EAR, mean 33% protection, P<0.05), completely blocked the
      late antigen-induced bronchoconstriction (LAR, mean 81% protection, P<0. 05) and
      the airway hyperresponsiveness (AHR, P<0.05) to aerosolized carbachol that occurs
      24 h after antigen challenge in this model. Consistent with this functional
      protection was a small but significant reduction in the percentage of neutrophils
      recovered in bronchoalveolar lavage (BAL) at 8 h and 24 h after challenge. These
      findings are similar to previous data obtained in this animal model with other 5
      LO inhibitors (blockade of the LAR and AHR) and COX inhibitors (blockade of AHR).
      These results suggest that aerosol administration of a dual inhibitor of COX and
      5-LO may have beneficial effects in the treatment of allergic airway disease.

PMID- 9514634
TI  - Details of Forthcoming Conferences
AB  - No Abstract

PMID- 9514632
TI  - Call for Papers: The Journal of Adolescence - Special Issue- Peer-led
      Interventions
AB  - No abstractCopyright 1997The Association for Professionals in Services for
      Adolescents.

PMID- 9514635
TI  - Identification of iron-regulated proteins of Mycobacterium tuberculosis and
      cloning of tandem genes encoding a low iron-induced protein and a metal
      transporting ATPase with similarities to two-component metal transport systems.
AB  - Iron plays a central role in the pathogenesis of Mycobacterium tuberculosis, the
      principal causative agent of tuberculosis. To learn more about iron acquisition
      by this bacterium, its iron regulated proteins (IRPs) were investigated. Seven
      IRPs were identified - three increased by high iron concentrations, and four by
      low iron concentrations. The smallest protein induced by low iron, Irp10, is
      tightly iron regulated as it is virtually absent in bacteria cultured in the
      presence of high iron concentrations. The gene (irpA ) encoding this protein and
      an adjacent open reading frame, mtaA, were cloned and sequenced. The protein
      encoded by mtaA (Mta72) has striking homology to metal transporting P-type
      ATPases. This study suggests that Irp10 and Mta72 function as a two-component
      metal transport system in M. tuberculosis.

PMID- 9514636
TI  - Involvement of glutamic acid residue at position 7 in the formation of the
      intramolecular disulfide bond of Escherichia coli heat-stable enterotoxin Ip in
      vivo.
AB  - Escherichia coli heat-stable enterotoxin Ip (STIp) is a small peptide toxin
      composed of 18 amino acid residues containing three intramolecular disulfide
      bonds. We found previously that the bonds are formed by the catalysis of DsbA (a
      oxidoreductase) in periplasm [1]. To interact with DsbA, the STIp in periplasm
      must have a structure suitable as substrate. However, the amino acid residues
      contributing to the construction of this structure have not been elucidated. We
      mutated the codon for the glutamic acid at position 7 of STIp by oligonucleotide
      site-specific mutagenesis in vivo and analysed the STIp produced from the mutant
      gene. The intramolecular disulfide bonds were not formed in mutant STIp (Glu-7-
      >Ala), but were formed in mutant STIp (Glu-7-->Asp). Furthermore, we found that
      replacing the asparagine residue at position 11 and the proline residue at
      position 12 did not affect the disulfide bond formation of STIp. The results
      indicate that a negative charge at position 7 in the sequence of STIp is
      necessary for STIp to interact with DsbA in periplasm.

PMID- 9514637
TI  - Genetic and immunological analyses of Vls (VMP-like sequences) of Borrelia
      burgdorferi.
AB  - DNA fragments containing the VMP-like sequence (Vls) were cloned from Borrelia
      burgdorferi strain 297. Analyses by PCR, PFGE, and Southern hybridization
      revealed that the Vls sequences existed in multi-copies on the 20-kb borrelial
      plasmid, but not on chromosomes or other plasmids. One Vls unit of the strain 297
      was about 669 bases, and predicted peptides length was 223 amino acids.
      Homologues of the Vls fragment were detected in three B. burgdorferi strains, a
      B. garinii strain 20047, and a B. afzelii strain P/Gau. A recombinant VlsII
      protein prepared in Escherichia coli strain JM109 reacted with antibodies that
      existed in three of five patients, by immunoblotting. These results suggested
      that the Vls of B. burgdorferi is expressed in Lyme disease patients.

PMID- 9514638
TI  - Amino acid changes affecting the activity of pneumolysin alter the behaviour of
      pneumococci in pneumonia.
AB  - Pneumolysin is a multi-functional toxin produced by Streptococcus pneumoniae. The
      toxin has distinct cytotoxic activity and complement-activating activity mediated
      by different parts of the toxin molecule. Mice challenged intranasally with a
      type 2 pneumococcal strain contract bronchopneumonia and bacteremia [1]. Mice
      were infected intranasally with isogenic mutants of this strain in which the
      chromosomal pneumolysin gene carried point mutations affecting either or both
      properties of pneumolysin. Reduction in either cytotoxic activity or complement
      activation by pneumolysin decreased the virulence of the mutant pneumococci.
      However, it was the ability to activate complement that most affected the
      behaviour of pneumococci in the lungs and associated bacteremia in the first 24 h
      following infection.

PMID- 9514639
TI  - Heterogeneity in the organization of the CTX genetic element in strains of Vibrio
      cholerae O139 Bengal isolated from Calcutta, India and Dhaka, Bangladesh and its
      possible link to the dissimilar incidence of O139 cholera in the two locales.
AB  - After a lapse of 33 months, Vibrio cholerae O139, the new serogroup associated
      with cholera, has re-emerged in Calcutta, India and has become the dominant
      serogroup causing cholera from September 1996. In neighbouring Bangladesh, V.
      cholerae O1 biotype El Tor continues to be the dominant cause of cholera with the
      O139 serogroup accounting for only a small proportion of cases. Comparison of the
      phenotypic traits of representative O139 strains from Calcutta and Dhaka isolated
      between December 1996 and April 1997 showed similar phenotypic traits with the
      exception that Dhaka O139 strains were susceptible to streptomycin whilst
      Calcutta O139 strains were resistant. The Dhaka and Calcutta O139 strains
      displayed identical ribotypes but showed remarkable differences in the structure
      and organization of the CTX genetic element. In the Dhaka O139 strains, two
      copies of the CTX element were arranged in tandem and this resembled the pattern
      displayed by the 1992 epidemic strains of O139. The Calcutta O139 strains, in
      contrast, carried three copies of the CTX genetic element arranged in tandem with
      the loss of a conserved BglII restriction site in the RS1 element and the
      appearance of a new HindIII site in the same region. While there may be other
      factors, it appears that the reorganization of the CTX genetic element in the
      Calcutta O139 strains may have contributed to the resurgence of this serogroup in
      Calcutta.

PMID- 9514640
TI  - Influence of mycobacterial virulence and culture condition on gamma delta T cell
      activation.
AB  - Activation of human gamma delta T cells by culture supernatants of virulent and
      avirulent mycobacteria was examined. The stimulatory potential of mycobacteria
      was influenced by the type of culture media and independent from their virulence.
      Activation of gamma delta T cells by phagocytes infected with viable virulent
      Mycobacterium tuberculosis H37Rv and avirulent M. bovis BCG was comparable. We
      conclude that gamma delta T cell stimulation occurs in response to infection with
      mycobacteria independent from their virulence.

PMID- 9514641
TI  - V antigen of Yersinia pestis inhibits neutrophil chemotaxis.
AB  - V antigen (V), a secreted protein encoded by the 70 kb low-calcium response
      plasmid of Yersinia pestis, is an essential virulence factor. In animal models,
      it inhibits the early host inflammatory response to infection which is associated
      with decreased blood and tissue levels of proinflammatory cytokine synthesis. To
      elucidate further the pathogenetic mechanism(s) of V, in vitrosystems are needed
      to measure and analyse relevant functional activities of V. We studied the effect
      of V on the migration of neutrophils to a chemoattractant both in vivo and in
      vitro. Peripheral injection of V was associated with a reduction in the number of
      PMN migrating into s.c. sponges and i.p. exudates. Similarly, pre-incubating
      human peripheral blood neutrophils with >/=ng/ml V significantly inhibited the in
      vitro chemotactic response to the peptide chemoattractant FMLP. The inhibitory
      activity of V was inactivated by heat and was neutralized by rabbit polyclonal
      anti-V IgG as well as by sera from mice surviving infection with Y. pestis.
      Recombinant polyhistidine-tagged V fusion proteins retained biological activity
      compared to V proteins lacking the tag. Inhibition of chemotaxis appears to be
      the first demonstration of an in vitro biological effect of V and may be a useful
      model to elucidate its molecular mechanism of action.

PMID- 9514642
TI  - Predoctoral and Postdoctoral Research Fellowships
AB  - Copyright .

PMID- 9514645
TI  - The in vitro effect of lithocholic acid on the polymerization properties of PiZ
      alpha-1-antitrypsin.
AB  - We describe here an in vitro effect of lithocholic acid (LA), a secondary,
      hydrophobic bile acid, on the rate of polymerization of mutant, Z and wild-type,
      M alpha-1-antitrypsin (AAT). Using thioflavine T fluorescence and turbidity
      assays we demonstrated that the rate of aggregation for the Z AAT in the presence
      of LA at a molar ratio of 1:5 AAT to LA, in Tris-buffered saline, pH 7.4, is at
      least twice that of the Z protein alone or the M variant with and without LA.
      Also, Z AAT incubated for 48 h at room temperature had more than 50% diminished
      antielastase activity, while M AAT had only a 25% reduction in activity. Analysis
      of the AAT and AAT-LA samples after cleavage with pancreatic elastase by SDS-PAGE
      10% gels showed that interaction between Z or M AAT and LA abolishes their
      ability to form SDS stable complexes with an enzyme and both of these forms of
      AAT showed elastase substrate behavior. Furthermore, Z as well as M AAT incubated
      with LA at 41 degrees C and cleaved with elastase showed only 80 to 60% increased
      thermal stability compared to 100% stabilization for the cleaved AAT alone in the
      absence of LA. These observations suggest that a rearrangement of the AAT
      molecule as a result of interactions with LA increases aggregation of AAT and
      diminishes its inhibitory activity.

PMID- 9514644
TI  - Regulation by GTPgammaS of protein carboxylmethyltransferase activity in kidney
      brush border membranes.
AB  - The increase in carboxyl methylation induced by guanosine 5',3-O
      (thio)triphosphate (GTPgammaS) in brush border membranes from rat kidney cortex
      was studied, and the methyltransferase activities affected by this nucleotide
      analog were identified. Addition of GTPgammaS to brush border membranes
      stimulated the carboxyl methylation in a time-dependent manner while adenosine
      and guanine nucleotides were ineffective. The GTPgammaS-dependent carboxyl
      methylation was inhibited by the chelating agents EDTA (63%) and 1,10
      phenanthroline (68%), suggesting that this activity required divalent cations.
      The methyl ester groups induced by the addition of GTPgammaS to brush border
      membranes were unstable, with about 80% of them hydrolyzed following 1 h
      incubation at 37 degrees C. The GTPgammaS stimulation of the carboxyl methylation
      in brush border membranes was unaffected by the detergent 3-[(3cholamido)
      dimethylammonio]-1-propanesulfonic acid up to a concentration of 0.4% (w/v). At
      this latter detergent concentration, the activity of prenylated protein
      methyltransferase (PPMT) was strongly inhibited and that of l-isoaspartyl/d
      aspartylmethyltransferase (PIMT) was increased twofold, as measured with their
      respective exogenous substrates, N-acetyl-S-farnesyl cysteine and ovalbumin.
      GTPgammaS increased the methylation of several substrates in brush border
      membranes. The induced methylation in substrates migrating between 20 and 36 kDa
      was strongly decreased by the competitive inhibitor farnesylthioacetic acid, a
      synthetic farnesylated substrate for PPMT, while a delta-sleep-inducing peptide
      containing an L-isoaspartyl residue inhibited that of substrates with molecular
      weights above 36 kDa, suggesting that PIMT activity was also involved. This
      interpretation was strengthened by the observation that the increased methylation
      induced by GTPgammaS in these membrane substrates was completely lost following
      their analysis by gel electrophoresis under alkaline conditions. Taken together,
      these results indicate that both PPMT and PIMT activities are regulated by
      guanine nucleotides in brush border membranes of rat kidney.

PMID- 9514646
TI  - Electron transfer in ruthenium-modified spinach plastocyanin mutants.
AB  - Four site-directed mutants of spinach plastocyanin, Pc(Leu12His), Pc(Leu15His),
      Pc(Thr79His), and Pc(Lys81His), have been modified by covalent attachment of a
      photoactive [Ru(bpy)2(im)]2+ complex at the surface-exposed histidine residues.
      The Pc-Ru complexes were characterized with optical absorption, CD, and EPR
      spectroscopy and their spectra were found to be similar to the unmodified
      proteins except in the case of the Pc(Leu12His) mutant which lost the Cu ion
      irreversibly during the Ru modification. Electron transfer (ET) within the other
      Pc-Ru complexes was studied with time-resolved optical spectroscopy, using an
      external-quencher approach. The fully reduced [Cu(I), Ru(II)] proteins were
      photoexcited and subsequently oxidized by an external quencher, [Ru(NH3)6]Cl3,
      forming the [Cu(I), Ru(III)] proteins. This was followed by an internal ET from
      Cu(I) to Ru(III). The rates of the internal ET reactions exhibit an exponential
      dependence on metal-to-metal separation, with a decay factor of 1.1 A-1. From a
      temperature-dependence study of the Ru-modified Pc(Lys81His) protein, a
      reorganization energy for the Cu-to-Ru ET reaction of 1.2 eV was determined. In
      this analysis it was found necessary to include an appreciable temperature
      dependence in the driving force of the ET reaction.

PMID- 9514647
TI  - Effect of replacement of the tightly bound Ca2+ by Ba2+ on actin polymerization.
AB  - G-actin has a single tight-binding (high-affinity) site for divalent cations per
      mole of protein, whose occupancy is important for the stability of the molecule.
      Different tightly bound divalent cations differently influence the polymerization
      properties of actin. The tightly bound metal ion easily exchanges for free
      exogenous cations. Moreover, biochemical and structural evidence demonstrates
      that actin, in both the G- and F-forms, assumes different conformations depending
      on the metal ion bound with high affinity in the cleft between two main domains
      of the molecule. In this work, we used proteolytic susceptibility to detect
      possible local conformational alterations of the actin molecule following a brief
      incubation of Ca-G-actin with barium chloride and ethylene glycol-bis(beta
      aminoethyl ether)-N,N,N',N'-tetraacetic acid. We found that substitution of Ba2+
      for the tightly bound Ca2+ affects the regions around Arg-62 and Lys-68 in
      subdomain 2 of G-actin, as judged from inhibition of tryptic cleavage at these
      residues. Using the fluorescent chelator Quin-2, we observed that about 0.95 mol
      of Ba2+ is released per 1 mol of actin. We also examined the effect of
      replacement of the tightly bound Ca2+ by Ba2+ on actin polymerization. With
      respect to Ca-actin, Ba-actin shows an increased polymerization rate, mainly due
      to its enhanced nucleation and a higher critical concentration.

PMID- 9514648
TI  - Complex limiting behaviour of multilocus genetic systems in cyclical
      environments.
AB  - Here we demonstrate that complex limiting behaviour (supercycles and chaotic-like
      phenomena) may arise in a rather broad and natural class of multilocus systems,
      both haploid and diploid, experiencing stabilizing selection with cyclically
      varying optima over a short period. These include loci with purely additive,
      dominant, or semidominant effects, with different types of their chromosome
      distribution. The observed complex dynamics appeared to manifest a certain
      stability with respect to disturbances of parameters specifying the structure of
      the selected system and environmental characteristics. This mode of multilocus
      dynamics by far exceeds the potential attainable under ordinary selection models
      resulting in simple behaviour. It may represent a novel evolutionary mechanism
      increasing genetic diversity over long time periods. This novel mechanism could
      contribute to the observation that biological diversity has increased over
      geological time regardless of the well-known massive extinctions.

PMID- 9514649
TI  - Target cell limited and immune control models of HIV infection: a comparison.
AB  - We develop various mathematical models of the clinical latency stage of HIV-1
      infection assuming that HIV-1 infection is limited either by the availability of
      cells that HIV can infect or by a specific anti-HIV cellular immune response. The
      former models we call "target-cell-limited". Comparing the models by phase plane
      analysis we find that they all belong to the class of predator-prey models. In
      the target-cell limited models the virus is a predator feeding upon target cell
      prey, while in the immune-control models the virus is a prey that is controlled
      by an immune response predator. Because both classes of models are of predator
      prey type they behave similarly in most circumstances. We find that both types of
      model can account for the generic picture of disease progression in which the CD4
      T cell count slowly decreases and the viral load slowly increases. Additionally,
      we find that both types of models can adequately describe the clinically observed
      changes in the plasma HIV-1 RNA loads in response to retroviral therapies.

PMID- 9514650
TI  - Multiphasic growth models and the evolution of prolonged growth exemplified by
      human brain evolution.
AB  - New models for multiphasic growth are presented. They are illustrated by analysis
      of brain growth in humans and chimpanzees, and the results are used to test the
      hypothesis of evolution by proportional growth prolongation: that all descendant
      growth phases are extended by the same factor while each remains at the ancestral
      growth rate. The results are consistent with the hypothesis and imply that gross
      brain weight increase towards humans required change in only one growth
      parameter: prolongation of the nonlinear ancestral growth phases. The restricted
      and orderly nature of the developmental changes hints at a basis in few genetic
      changes. Proportional growth prolongation is of general evolutionary importance
      because it can reorganize body proportions.

PMID- 9514651
TI  - Path-based network unfolding: A solution for the problem of mixed trophic and non
      trophic processes in trophic dynamic analysis 
AB  - The purpose of this paper is to describe a quantitative method of trophic dynamic
      analysis derived from a systems ecology theoretical foundation. This method was
      devised to provide a solution for the problem of how to deal with mixed trophic
      and non-trophic processes in cyclic ecosystem networks, a problem that has vexed
      trophic ecology since Lindeman first presented a formal concept of trophic
      dynamics in 1942. The author's initial attempt to solve this problem was
      presented in Whipple & Patten (1993, J. theor. Biol. 163, 393-411). The path
      based network unfolding method described in this paper provides a quantitative
      method for conducting trophic dynamic analysis of cyclic ecosystems containing
      non-living storages and non-trophic flows to produce a true energy-transformation
      trophic macrochain. This method solves the "trophic-level inflation" problem
      described in Whipple & Patten (193, J. theor. Biol. 163, 393-411). The results of
      the analysis of an oyster reef ecosystem model demonstrate that the dual trophic
      macrochain produced by path-based network unfolding may be used to compare the
      relative contribution of grazing and detrital sub-webs to the trophic dynamics of
      ecosystems. It was found that the standing stock and flow contribution of the
      detrital sub-web was quantitatively dominant in the oyster reef ecosystem model.
      This method might be used to compare the contribution of grazing and detrital sub
      webs for models of different ecosystem types. Because a true energy
      transformation trophic chain is produced, the progressive efficiency concept of
      the Lindeman-Hutchinson paradigm may be applied in comparative trophic analyses
      of ecosystems. In comparing the oyster reef model results of three quantitative
      trophic analysis methods, the path-based network unfolding method was found to
      produce a trophic macrochain with progressive efficiencies intermediate between
      those produced by the original Higashi et al. method and the Burns et al.
      unfolding analysis of a modified version of the oyster reef model.Copyright 1998
      Academic Press Limited

PMID- 9514652
TI  - The steady states of microbial growth on mixtures of substitutable substrates in
      a chemostat.
AB  - Microbes growing on mixtures of substrates in a chemostat exhibit different
      substrate utilization patterns, depending on the dilution rate and feed
      concentrations. For instance, when supplied with high feed concentrations of a
      binary mixture, both substrates are consumed at low dilution rates, but only one
      of the substrates is consumed at high dilution rates. The goal of this work is to
      explain the onset of such transitions, which play a very significant role in
      ecology and bioengineering. In previous work, we formulated a mathematical model
      of mixed-substrate growth in batch cultures. We use the extension of this model
      to continuous cultures as the framework for understanding substrate utilization
      patterns in continuous cultures. Our explanation rests upon the existence of two
      special types of dilution rates predicted by the model. The first is the so
      called critical dilution rate at which the growth rate becomes zero, leading to
      cell washout. The existence of the critical dilution rate obtains from the
      simplest models of microbial growth, and is rooted in the fact that growth is
      inherently autocatalytic. The second type of special dilution rate, a unique
      feature of our model, stems from the recognition that synthesis of the enzymes
      catalysing the uptake of substrates is also autocatalytic. Hence, associated with
      each substrate is a transition dilution rate at which the synthesis rate of the
      transport enzyme becomes zero. We show that: (1) the substrate utilization
      patterns in continuous cultures are completely determined by the relative
      magnitudes of the critical and transition dilution rates; and (2) the critical
      and transition dilution rates are in turn determined by the feed concentrations.
      This allows us to construct an operating diagram, which yields the substrate
      utilization pattern for any given dilution rate and feed concentrations. The
      theory explains most of the mixed-substrate phenomena summarized in a recent
      review article by Egli (1995, Adv. Microbiol. Ecol. 14, 305-386).

PMID- 9514653
TI  - Optimal dispersal range and seed size in a stable environment 
AB  - The evolutionary stable (ESS) dispersal range for annual plants is studied in a
      stable environment when there is a trade -off between seed survivability and
      dispersal range via seed size. Larger seed size is more beneficial in the
      competition for safe sites, but likely to be dispersed a shorter distance and to
      suffer competition among siblings. Previously Hamilton & May found that dispersal
      can be adaptive in a stable environment to reduce competition among sibs, but
      they assumed that dispersers were likely to enter all the patches equally-this is
      not suitable for many terrestrial plants with limited dispersal range. In this
      article I discuss the evolution of dispersal range for wind dispersed seeds when
      dispersal range is tightly coupled with seed size. I assume that the density of
      dispersed seed follows a two-dimensional normal distribution function, with
      variance decreasing with seed size. Due to the trade-off between the seed number
      and the survivability of a seedling offspring, there is a seed size &wtilde; that
      maximizes the product of the two quantities. This is the optimal seed size when
      size-dependent dispersal is neglected. The ESS seed size considering the size
      dependent dispersal w* is also calculated by neglecting the effect of spatial
      clumping of relatives. Under the environment unfavorable for seed dispersal, the
      ESS seed size w* can be much smaller than the optimal seed size &wtilde;, but
      there is a lower limit for the ESS dispersal range even in the extremely sticky
      environment. Even if the dependency of seed survivability on the seed size is so
      weak that the cost of long-range dispersal is small, the ESS seed dispersal range
      cannot become very large. These results are confirmed by individual-based
      computer simulations with more realistic assumptions considering spatial clumping
      of non-sib relatives.Copyright 1998 Academic Press Limited

PMID- 9514654
TI  - Characterization of two cDNA clones which encode O-methyltransferases for the
      methylation of both flavonoid and phenylpropanoid compounds.
AB  - Enzymatic O-methylation of phenylpropanoid and flavonoid compounds is believed to
      be catalyzed by distinct classes of O-methyltransferases [EC 2.1.1.6x]. The O
      methylated derivatives of phenylpropanoids and flavonoids play an important role
      in lignification and as antimicrobial compounds, respectively. Two cDNA clones,
      OMT1 and OMT2, which differ in three amino acid residues were isolated and
      characterized from the semiaquatic freshwater weed Chrysosplenium americanum
      (Saxifragaceae). These two novel cDNA clones encode enzymes which catalyze the 3'
      O-methylation of the flavonoid aglycones luteolin and quercetin, although they
      also catalyze the efficient 3/5-O-methylation of the phenylpropanoids caffeic and
      5-hydroxyferulic acids, respectively. Both recombinant proteins were partially
      purified from an Escherichia coli expression system and their kinetic parameters
      were compared using two flavonoids and two phenylpropanoids as substrates.
      Although both gene products methylate caffeic acid and 5-hydroxyferulic acid to a
      similar extent, they exhibit a threefold higher affinity for and a four- to
      sixfold increase in turnover of flavonoid compounds. The gene product of OMT1
      accepts the flavonoid substrates luteolin and quercetin for methylation at a
      higher rate than that of OMT2, as indicated by a two- to threefold increase in
      its Vmax values and turnover ratios. The fact that C. americanum accumulates a
      variety of highly methylated flavonols and exhibits little lignification suggests
      that these two flavonoid OMT clones have retained their ability to O-methylate
      phenylpropanoids as well. These results are discussed in relation to differences
      in the amino acid sequences of these two clones, as well as with other O
      methyltransferases, and the evolutionary divergence of these genes in plants.

PMID- 9514655
TI  - Modulation of prostaglandin H synthase-2 mRNA expression by 2,3,7,8
      tetrachlorodibenzo-p-dioxin in mice.
AB  - Prostaglandin endoperoxide H synthases (PGHS-1 and PGHS-2) catalyze an
      intermediate step in the biosynthesis of prostaglandins and thromboxanes.
      Recently, it was observed that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)
      modulates the expression of PGHS-2 mRNA in different cell lines. The main aim of
      this study was to examine whether PGHS-2 mRNA expression can be changed by acute
      TCDD in vivo and, second, we were also interested in whether modulation of PGHS-2
      is mediated by the aryl hydrocarbon receptor (AhR) which is known to be involved
      in the transcriptional control of TCDD-induced phase 1 and phase 2 enzymes.
      Initially C57BL/6J mice were treated with a single dose of 10,000 ng TCDD/kg and
      the PGHS-1 and PGHS-2 mRNAs were analyzed in liver, lung, thymus, kidney, and
      spleen. In all tissues examined the expression of PGHS-1 mRNA was not affected by
      TCDD. However, TCDD treatment enhanced the PGHS-2 mRNA levels in lung and spleen.
      No effect of TCDD on PGHS-2 expression was found in liver and kidney. For dose
      response studies C57BL/6J and DBA/2J mice were treated for 24 h with various
      doses of TCDD (1-50,000 ng/kg) and the PGHS-2 mRNA increases were analyzed in
      lungs and spleens. A significant increase of PGHS-2 mRNA in lungs of C57BL/6J
      mice was found at a dose of 100 ng TCDD/kg, whereas a nearly 100-fold higher TCDD
      dose was needed to increase PGHS-2 in DBA/2J mice. A similar dose-dependent
      induction of PGHS-2 was found in spleens of C57BL/6J mice; however, no
      significant increase of PGHS-2 was found in spleens of DBA/2 mice. These results
      indicate an involvement of AhR in TCDD-mediated changes of PGHS-2 expression.
      This suggestion is supported by studies in AhR-deficient animals which showed
      that TCDD had no effect on PGHS-2 mRNA. When changes of PGHS-2 mRNA expression
      are compared with those of CYP1A1 between 4 and 72 h after TCDD, it is noteworthy
      that TCDD led to a delayed and more transient increase of PGHS-2. These data
      suggest that the mechanism of modulation of both genes by TCDD may be different.

PMID- 9514657
TI  - Spatial dynamics and critical patch size of annual plant populations 
AB  - Critical patch size is the minimum habitat size required for population
      persistence. The critical patch size of an annual plant population residing in a
      finite homogeneous habitat, using an integro-difference equation model is
      considered and this is found to be dependent on the basic population growth rate
      and dispersal characteristics. General analytical and numerical methods for the
      calculation of the critical patch size are presented with the inclusion of a
      simple new approximation technique. These methods are illustrated in the context
      of a species dispersing seeds on a Gaussian distribution. The approach is
      extended to incorporate a persistent seed-bank. Where the dispersion of seeds
      entering the seed-bank and those giving rise to adult plants is identical, the
      possession of a seed-bank influences the critical patch size through a scaling of
      the basic population growth rate. The wider implications of the approach are
      discussed in the context of metapopulation dynamics.Copyright 1998 Academic Press
      Limited

PMID- 9514656
TI  - Compensatory responses to inhibition of hepatic squalene synthase.
AB  - The mechanism by which depletion of hepatic cholesterol levels, achieved by
      inhibition of squalene synthase, alters hepatic LDL receptor, HMG-CoA reductase,
      and cholesterol 7alpha-hydroxylase gene expression was investigated by measuring
      transcription rates, mRNA stability, rates of translation, translational
      efficiency, and levels of sterol response element binding proteins. It was found
      that the transcription of both hepatic LDL receptor and HMG-CoA reductase were
      increased about twofold. The increase in LDL receptor transcription occurred
      within 2 h after giving 2 mg/kg zaragozic acid A, a potent inhibitor of squalene
      synthase. This preceded the increase in transcription of HMG-CoA reductase that
      occurred at 4 h. Increases in the stability of both of these mRNAs were also
      observed. These changes account for the increases in LDL receptor and HMG-CoA
      reductase mRNA levels previously observed. The rate of transcription of hepatic
      cholesterol 7alpha-hydroxylase was decreased to about 25% of control within 3 h
      after administration of zaragozic acid A, which correlates with the decrease in
      this mRNA. The rates of translation, as determined by pulse labeling, of both
      hepatic HMG-CoA reductase and LDL receptor were increased two- to threefold. The
      translational efficiency of these two mRNAs was also increased as judged by
      polysome profile analysis. There was an increase in mRNA associated with the
      heaviest polysome fraction and a decrease in that associated with monosomes. No
      significant change was observed in the levels of sterol response element binding
      protein 2, the form that mediates induced transcription, in response to zaragozic
      acid A treatment, indicating that this protein might not be involved in mediating
      the observed transcriptional changes. An increase in sterol response element
      binding protein -1 was observed 30 min after giving zaragozic acid A. The results
      suggest that compensatory responses to depletion of squalene-derived products
      involve alterations in the rates of transcription, mRNA stability, and
      translational of key proteins involved in cholesterol homeostasis.

PMID- 9514658
TI  - Horseradish peroxidase: partial rescue of the His-42 --> Ala mutant by a
      concurrent Asn-70 --> Asp mutation.
AB  - In horseradish peroxidase (HRP), hydrogen bonding of Asn-70 to His-42 enhances
      the catalytic activity of the histidine, and mutation of His-42 to a neutral
      residue greatly decreases peroxidase activity. The N70D/H42A HRP mutant is
      compared here to the previously characterized H42A mutant to determine if the Asp
      70 substitution can rescue the catalytic activity. The N70D/H42A and H42A mutants
      give Compound I species with a high ratio of H2O2 at the low rates of 37 and 81 M
      1 s-1 at 4 degrees C, respectively. The kcat values for the oxidation of guaiacol
      and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) by N70D/H42A
      HRP are 2.7 and 143 s-1, respectively, compared to values of 0.015 and 0.41 s-1
      for the H42A mutant. The kcat values for thioanisole sulfoxidation by the
      N70D/H42A and H42A mutants are 0.18 and 0.03 s-1, respectively, and the
      corresponding values for styrene epoxidation are 0.005 and 0.007 s-1. Due to
      changes in the substrate Km values, the efficiencies of the N70D/H42A and H42A
      mutants defined by kcat/Km are guaiacol, 5 vs 4; ABTS, 286 vs 68; thioanisole, 3
      vs 0.1; and styrene, 0.025 vs 0.002, respectively. The N70D mutation in N70D/H42A
      HRP thus increases the activity versus the H42A mutant with respect to all four
      substrates. The increased efficiency is due to enhancements in catalytic steps
      other than the formation of Compound I.

PMID- 9514659
TI  - Substrate specificity of acyl-CoA:Lysophospholipid acyltransferase (LAT) from pig
      spleen.
AB  - The present investigation was undertaken to gain insights into the nature of both
      substrate binding sites of acyl-CoA:lysophospholipid acyltransferase (LAT) which
      could be potentially useful for the identification and purification of this
      specific acyltransferase. Therefore, we have investigated the specificity of LAT
      from crude membranes of pig spleen toward various 1-palmitoyl
      glycerophospholipids and 1-acyl-glycerophosphocholines (1-acyl-GPC). The enzyme
      showed the highest specificity toward 1-acyl-GPC and was able to distinguish
      between the acyl-chain length of the 1-acyl group within the 1-acyl-GPC molecule.
      We found preferential reactivity in the order C10:0 < C12:0 << C14:0, C18:0,
      C16:0 < C18:1 of 1-acyl-GPC. Lysophosphatidic acid or 1-O-alkyl-GPC were only
      poor substrates for the enzyme. In competition studies we could show that
      palmitic acid, oleic acid, arachidonic acid, and palmitoyl-CoA competitively
      inhibited LAT activity, whereas the coenzyme A failed to inhibit LAT enzyme
      activity in a concentration-dependent manner. We concluded that the ligand acyl
      CoA is bound via its acyl chain. The finding that palmitoyl-CoA was a poor
      substrate as well as an inhibitor was the basis for protein purification. When
      palmitoyl-CoA-agarose was used as matrix for affinity chromatography, LAT enzyme
      activity was bound and eluted by high salt concentrations yielding an estimated
      10-fold purification of the solubilized LAT enzyme.

PMID- 9514660
TI  - Characterization of the intracellular and the plasma membrane Ca2+-ATPases in
      fractionated pig brain membranes using calcium pump inhibitors.
AB  - The Ca2+-ATPase activity of isolated membranes and purified plasma membrane
      ATPase from pig brain was measured in the presence of specific inhibitors. The
      inhibition of the enzymatic activity by vanadate presents a lower affinity in
      microsomes than in the synaptic plasma membrane vesicles, showing K0.5 of 0.4 and
      0.2 microM, respectively. The purified enzyme showed a higher sensitivity to
      vanadate with a K0.5 of 0.10 microM. Thapsigargin (Tg) and 2,5-di(tert-butyl)-1,4
      benzohydroquinone (BHQ) were stronger inhibitors of the Ca2+-ATPase activity in
      microsomes than in the synaptic membrane vesicles. The activity of the purified
      enzyme was not affected by Tg and only partially by BHQ. Cyclopiazonic acid
      inhibited the enzymatic activity in all fractions, being more sensitive in
      microsomes. The microsome preparation incorporated 32P from [gamma-32P]ATP into
      two main proteins that appear at approx 110,000 and 140,000. According to the
      inhibition pattern, the lower phosphorylated band was identified as the
      sarco(endo)plasmic reticulum Ca2+-ATPase, being in a higher percentage than the
      upper band. Synaptic membrane vesicles also incorporated radioactive 32P into two
      protein bands. The 140,000 protein (upper band) shows the typical behavior of the
      purified plasma membrane Ca2+-ATPase, being more abundant in this preparation
      than the organellar Ca2+-pump (lower band). This study highlights the
      heterogeneous nature of the Ca2+-ATPase activity measured in brain membrane
      fractions.

PMID- 9514661
TI  - Chlorogenic acid analogue S 3483: a potent competitive inhibitor of the hepatic
      and renal glucose-6-phosphatase systems.
AB  - S 3483, a synthetic derivative of chlorogenic acid (CHL), was found to be a
      reversible, linear competitive inhibitor of the glucose-6-phosphatase (Glc-6
      Pase) system in rat renal microsomes and rat and human liver microsomes. The Ki
      for S 3483 in rat liver microsomes (129 nM) is three orders of magnitude smaller
      than the Ki for CHL. S 3483 up to 100 microM had no effect on the Glc-6-Pase
      enzyme activity or on the system inorganic pyrophosphatase activity (i.e., on T2,
      the Pi/inorganic pyrophosphate transporter). Thus, like CHL, S 3483 appears to be
      a site-specific inhibitor of T1, the Glc-6-P transporter of renal and liver
      microsomes. The potency of S 3483 was unaffected when the ratio
      Vmax(T1):Vmax(enzyme) was altered over a 10-fold range by applying enzyme
      inhibition and selective inactivation of T1. The absence of T1-imposed rate
      restrictions on the potency of reversible T1 inhibitors contrasts markedly with
      the response of reversible Glc-6-Pase enzyme inhibitors, whose potency declines
      sharply as T1 becomes more rate controlling. The potency of S 3483, but not of
      CHL, decreased as the microsomal protein concentration in the assay medium was
      increased. This effect suggests that as the protein concentration was raised the
      concentration of T1 in the assay medium approached the order of magnitude of the
      Ki for S 3483. Thus, the microsomal content of T1 is likely to be on the order of
      100 pmol/mg protein. S 3483 is the most potent inhibitor of the Glc-6-Pase system
      reported to date. It and other tight-binding inhibitors of T1 will provide useful
      new tools for investigating the molecular structure and physiology/pathology of
      the Glc-6-Pase system.

PMID- 9514664
TI  - Matching of acoustic features during the vocal exchange of coo calls by Japanese
      macaques
AB  - A central issue in studies of vocalizations of non-human primates is the extent
      of their plasticity. Japanese macaques, Macaca fuscata, frequently utter coo
      calls and exchange these calls with other group members to maintain contact
      vocally. I conducted a playback experiment to examine whether monkeys that
      respond vocally match the acoustic features of their reply to those of the calls
      they have heard. Six to eight stimulus calls with different acoustic properties
      in terms of fundamental frequency components were played back to each of seven
      females, in an attempt to elicit replies from the subjects. There were
      significant positive regressions of the frequency range of stimuli with that of
      the replies. Japanese macaques thus matched some of the acoustic features of
      their replies to those of the preceding calls, suggesting that they might be able
      to modify the acoustic features of their calls according to the features of the
      prior calls of another group member.Copyright 1998 The Association for the Study
      of Animal Behaviour Copyright 1998 The Association for the Study of Animal
      Behaviour.

PMID- 9514663
TI  - Biochemical defense mechanisms against copper-induced oxidative damage in the
      blue crab, Callinectes sapidus.
AB  - The blue crab (Callinectes sapidus) has a very dynamic copper metabolism
      associated with the biosynthesis and degradation of its respiratory pigment
      hemocyanin. In this study we report on the cellular defense mechanisms used by
      the crab to protect itself from copper toxicity. Short-term copper-exposure
      studies, conducted by incubating hepatopancreas tissue explants in copper
      containing medium, show that copper taken up by the cells during the first 60 min
      combines with low-molecular-weight copper complex(es), which include Cu(I)
      glutathione. Thereafter, copper binds to newly synthesized metallothionein (MT),
      with a concomitant decrease in Cu(I)-glutathione. Copper does not displace zinc
      from the endogenous ZnMT pool. Long-term exposure by means of copper-rich diets
      results in the synthesis of two MT isoforms in the hepatopancreas: CuMT-I and
      CuMT-II (D. Schlenk and M. Brouwer, 1991, Aquat. Toxicol. 20, 25-34). Transfer of
      copper from Cu(I)-glutathione to apoMT-I and apoMT-II can be accomplished in
      vitro. Cu(I) binding by the two isoforms is very different. Cu(I) binds to apoMT
      I in a strictly cooperative manner. No partially filled Cu(I)-thiolate clusters
      appear to be present. In contrast, the Cu(I)-thiolate clusters in MT-II are
      formed only after more than four Cu(I) ions are bound. Long-term copper exposure
      leads to increased activity of two antioxidant enzymes: glutathione peroxidase
      and manganese superoxide dismutase (SOD). No CuZnSOD is found. Activities of
      catalase and glutathione reductase and the intracellular levels of glutathione
      are unaffected by copper. The defense mechanisms are not entirely sufficient for
      preventing copper-induced oxidative damage. Levels of oxidized lipids are
      significantly higher in copper-exposed crabs, but oxidized protein levels are
      nearly the same.

PMID- 9514662
TI  - Preparation and partial structural characterization of alpha1T-glycoprotein from
      normal human plasma.
AB  - alpha1T-glycoprotein (alpha1T) was isolated from normal human plasma in the
      immunochemically homogeneous state. The partial amino acid sequence and
      carbohydrate chains of this glycoprotein were determined. To achieve this, the
      carboxymethylated alpha1T was analyzed by sequencing some of the
      lysylendoprotease, V8 protease, tryptic, and cyanogen bromide peptides as well as
      the N-terminal sequence of the protein. A large number of amino acid residues
      (460 amino acids) was determined by chemical procedure. The peptide sequences
      were compared with that of other proteins. A high degree of homology was found
      for proteins of the albumin family. Further, human alpha-albumin, a new member of
      this protein family, showed an amino acid sequence identical to that of alpha1T
      indicating that these two proteins are very similar in amino acid sequence and
      composition. These proteins are closely related to alpha-fetoprotein; however,
      five carbohydrate chains were found on alpha1T at Asn12, Asn88, Asn362, Asn381,
      and Asn467 as biantennary complex type chains and the chain on Asn362 possessed a
      rare consensus sequence of Asn-X-Cys. Thus, alpha1T distinguishes itself by
      possessing five N-glycans, a finding reported here for the first time for the ALB
      family.

PMID- 9514665
TI  - Patch sampling behaviour and future foraging expectations in Argentine ants,
      Linepithema humile
AB  - Nests of Argentine ants, L. humile, were exposed to pairs of foraging patches of
      varying quality. These patches varied from never having food to having food for 4
      h every day. After 15 days, colonies were allowed an added access to a new patch.
      The new patch, however, never contained food. The sampling behaviour of nests
      towards the initial patches and the new patch suggested that the nests were using
      a sampling rule based on maximizing net benefits of finding food minus the cost
      of sampling. The behaviour of the nests towards the new patch was also
      significantly affected by what the foraging workers had previouisly encountered
      in the foraging patches. The behaviour of the L. humile colonies is similar in
      pattern to what would result by Bayesian updating of expectations for success in
      novel foraging opportunities. These data are the first suggestions of such an
      ability in an insect. Copyright 1998 The Association for the Study of Animal
      Behaviour Copyright 1998 The Association for the Study of Animal Behaviour.

PMID- 9514666
TI  - Mate-choice copying in Japanese quail, Coturnix coturnix japonica
AB  - We performed four experiments to examine effects on the mate choices of female
      Japanese quail, Coturnix coturnix japonica, of observing a male mate with another
      female. Each experiment was conducted in three phases: (1) a pre-test during
      which subject females were allowed to choose between two males with which to
      affiliate; (2) an observation phase, in which subject females either watched or
      did not watch the male they had spent less time near during the pre-test (their
      'non-preferred' male) copulate with a 'model' female; and (3) a post-test when
      subject females again chose between non-preferred and preferred males. Only
      females that had watched their non-preferred male mate with a model female during
      the observation phase spent significantly more time affiliating with him during
      the post-test than they had during the pre-test. Watching mating did not change
      females' criteria for choosing males, and non-preferred males that had mated
      recently were no more attractive to females than were non-preferred males that
      had not done so, unless subject females actually observed the mating take place.
      The results were consistent with the hypothesis that female quail copy one
      another's mate choices. Copyright 1998 The Association for the Study of Animal
      Behaviour Copyright 1998 The Association for the Study of Animal Behaviour.

PMID- 9514667
TI  - Effects of relatedness on queen competition within honey bee colonies
AB  - The influence of relatedness on the pre- and post-emergent survival of honey bee
      queens was investigated. Workers did not preferentially rear sisters over non
      siblings under conditions of natural queen replacement. After queen emergence,
      however, there was a significant effect of a queen's relatedness to the workers
      on her survivorship during fights with rival queens. The mechanism of this bias
      towards related queens is unknown, and several hypotheses are discussed. The
      difference in post-emergent survivability suggests that kin selection may operate
      during competition among adult queens at this crucial stage of honey bee
      reproduction. Copyright 1998 The Association for the Study of Animal Behaviour
      Copyright 1998 The Association for the Study of Animal Behaviour.

PMID- 9514668
TI  - Red squirrels, Tamiasciurus hudsonicus, produce predator-class specific alarm
      calls
AB  - Red squirrels, can produce alarm calls when they detect a potential predator.
      Observations of natural interactions between red squirrels and large birds, and
      predator-presentation experiments in the field, showed that red squirrels produce
      acoustically different alarm calls in response to aerial danger (live birds and a
      model hawk flown towards them) versus danger approaching from the ground (dogs
      and humans). The alarm call produced in response to aerial danger is acoustically
      convergent on the 'seet' alarm call produced by many species of passerine birds
      in response to raptors. The squirrels' 'seet' alarm is a short, low-amplitude,
      high-frequency call. These characteristics make the call difficult to localize,
      and is in a frequency range that is poorly perceived by raptors. Red squirrels
      produce much louder, wide-bandwidth bark calls in response to terrestrial danger.
      This is the first demonstration of predator-class specific alarm calls of red
      squirrels. Copyright 1998 The Association for the Study of Animal Behaviour
      Copyright 1998 The Association for the Study of Animal Behaviour.

PMID- 9514669
TI  - Yellow-bellied marmot and golden-mantled ground squirrel responses to
      heterospecific alarm calls
AB  - When two species have predators in common, animals might be able to obtain
      important information about predation risk from the alarm calls produced by the
      other species. The behavioural responses of adult yellow-bellied marmots, Marmota
      flaviventris, and golden-mantled ground squirrels, Spermophilus lateralis, to
      conspecific and heterospecific alarm calls were studied to determine whether
      interspecific call recognition occurs in sympatric species that rarely interact.
      In a crossed design, marmot and squirrel alarm calls were broadcast to
      individuals of both species, using the song of a sympatric bird as a control.
      Individuals of both species responded similarly to conspecific and heterospecific
      anti-predator calls, and distinguished both types of alarms from the bird song.
      These results indicate that both marmots and squirrels recognized not only their
      own species' anti-predator vocalizations, but also the alarm calls of another
      species, and that these vocalizations were discriminated from an equally loud non
      threatening sound. These findings suggest that researchers ought to think broadly
      when considering the sources of information available to animals in their natural
      environment. Copyright 1998 The Association for the Study of Animal Behaviour
      Copyright 1998 The Association for the Study of Animal Behaviour.

PMID- 9514670
TI  - Early handling increases lamb affinity for humans
AB  - Domestic animals that are socialized to humans are often more easily managed and
      less timid than those that are not. We examined whether increased handling and
      artificial feeding of domestic sheep, Ovis aries, at an early age would decrease
      their subsequent timidity towards people. Forty-eight lamb twin sets were divided
      into four treatment groups for 2 days of treatment at ages 1-3, 3-5, 5-7 or 7-9
      days. Treatment lambs were fed milk replacer and were handled four times/day for
      5-min periods. Their twins, used as controls, were left with their dams. Two 5
      min tests of lamb temperament were conducted at ages 2, 4, 6, 8, 10, 15 and 25
      days. Testing consisted of a stationary human encounter, in which lambs'
      responses to a sitting person were recorded continuously, and a moving human
      encounter, in which lambs' responses to a person walking at 0.5 m/2 s were
      recorded by instantaneous scans. Measures included latency to proximity (<2 m)
      and arm's reach (<1 m) of the person, time spent in proximity and within arm's
      reach, average distance (m), mean number of human contacts, number of lambs
      contacting a person and following/approach/avoidance. Treatment lambs showed
      significantly greater affinity for humans than their twin controls. The 1-3-day
      treatment group showed the greatest response to treatment, consistently
      outperforming controls in all of the above measures. These results suggest that
      40 min of positive human contact at age 1-3 days reduces lamb timidity to people.
      Socialization of lambs to humans need not disrupt the primary lamb-dam bond, and
      it may have positive management as well as welfare implications.?C 1998 The
      Association for the Study of Animal Behaviour Copyright 1998 The Association for
      the Study of Animal Behaviour Copyright 1998 The Association for the Study of
      Animal Behaviour.

PMID- 9514671
TI  - Extra-pair mating effort of male hooded warblers, Wilsonia citrina
AB  - Few researchers have been able to quantify the time or effort expended by male
      birds in seeking extra-pair copulations with neighbouring females. In this study,
      we radio-tracked male hooded warblers, to determine the frequency and duration of
      intrusions onto neighbouring territories. Extra-pair fertilizations are common in
      hooded warblers, with 35% of females producing extra-pair young. Males intruded
      onto territories where females were nest building more often than expected by
      chance and approached females during most intrusions (78%), suggesting that these
      intrusions were extra-pair copulation attempts. Almost all intrusions (96%) were
      to adjacent territories, and males made an average+/-se of 0.4+/-0.2 forays/h and
      spent 4.7+/-2.6% of their time off-territory. Males were involved in fights or
      chases with the resident male in 21% of intrusions, but were apparently
      undetected during most intrusions. Males with high intrusion effort onto
      neighbouring territories had the lowest rate of intrusions onto their own
      territory by other radio-tracked males. Males varied extensively in their
      intrusion effort, but this was not significantly correlated with male body mass,
      age or song rate. The percentage of time spent intruding onto other territories
      was small (0-8%), so males probably do not face strong trade-offs between making
      extra-pair copulation forays and other activities like mate guarding and feeding
      offspring. Copyright 1998 The Association for the Study of Animal Behaviour
      Copyright 1998 The Association for the Study of Animal Behaviour.

PMID- 9514672
TI  - Female behaviour, sexual competition and mate guarding in the blue crab,
      Callinectes sapidus
AB  - Blue crabs mate immediately after the female's final moult. We tested the
      influence of female moult stage, sex ratio and male size on the pre-mating
      behaviour of both sexes, and the ability of males to pair with females and
      aggressively compete for access to females. We observed crabs in field enclosures
      and surveyed pre-copulatory mate-guarding patterns in the field. Female behaviour
      changed as they progressed through the final moult cycle, such that early moult
      stage females avoided males, but late moult-stage females initiated pair
      formation. The changes in female behaviour influenced both the behaviour and
      pairing capability of males. Males courted and paired with late moult-stage
      females on their first attempt, but pursued early moult-stage females because
      their first attempts to pair often failed. In the field, early moult-stage
      females were paired less often than late moult-stage females. The pre-mating
      behaviour of both sexes also varied with sex ratio; when males were abundant,
      males traded courtship for forced capture and females courted less. Large males
      were more successful at take-overs, but did not pair more often with late moult
      stage females, suggesting that large males do not consistently guard for less
      time than small males. The changes in female behaviour are consistent with the
      female's need to avoid the costs of guarding and suggest that females influence
      how pre-copulatory mate guarding occurs in this species.Copyright 1998 The
      Association for the Study of Animal Behaviour Copyright 1998 The Association for
      the Study of Animal Behaviour.

PMID- 9514673
TI  - Producers, scroungers and the price of a free meal
AB  - In social foraging, scroungers take a disproportionately large share of the food
      found relative to their own food-searching efforts, while producers find more
      food than they manage to monopolize. We present a model of social foraging
      acknowledging the finder's advantage and foraging role asymmetries among
      individuals but incorporating the possibility that producers and scroungers
      differ in vigilance level and in vulnerability to predators. This allows
      simultaneous examination of both foraging benefits and anti-predatory aspects of
      grouping behaviour. Instead of seeking for equal payoff conditions, we first look
      for groups in which foraging character combinations and anti-predatory properties
      of producers and scroungers minimize the phenotype-specific predation hazard over
      food-intake rate, Ri/Ii, that is, fixed phenotype Ri/Ii minima. In the second
      approach, we allow individuals to change their foraging status to achieve lower
      Ri/Ii and look for combinations where it no longer pays for either producers or
      scroungers to change their roles, that is, evolutionarily stable group
      compositions, ESS. Various character combinations allow the phenotype-specific
      minima. In most cases, however, producers' and scroungers' minima are achievable
      only in different group compositions. The ESS combinations of producers and
      scroungers deviate widely from those combinations yielding phenotype-specific
      minima of Ri/Ii. If individuals are allowed to be flexible in adopting either a
      producer or a scrounger role, ESS group compositions will emerge, even though
      they are more expensive for both producers and scroungers in terms of Ri/Ii than
      group compositions yielding the phenotype-specific Ri/Ii minima. Copyright 1998
      The Association for the Study of Animal Behaviour Copyright 1998 The Association
      for the Study of Animal Behaviour.

PMID- 9514674
TI  - Soldiers effectively defend aphid colonies against predators in the field
AB  - Morphologically specialized soldiers occur in more than 50 aphid species in the
      families Pemphigidae and Hormaphididae. To study the effectiveness of soldiers of
      the gall-forming aphid, Pemphigus spyrothecae Pass., in protecting their galls
      against natural levels of predation, we manipulated the proportions of soldiers
      and non-soldiers in sets of galls still attached to poplar trees in the field.
      Galls with 50 soldiers and 50 non-soldiers were approximately 10 times less
      likely to be attacked by predators than galls that contained 100 non-soldier
      aphids. There were significantly fewer live aphids, and significantly more dead
      aphids, in galls without soldiers than in galls protected either by soldiers or
      by being within a bag. There were no significant differences in the survival of
      aphids in galls protected by soldiers compared with those protected by bagging.
      The soldiers did not protect the galls against invasion by the cohabiting aphid
      Chaitophorus leucomelas Koch. These observations provide the first demonstration
      that soldiers are effective in defence against natural levels of predation under
      field conditions. Copyright 1998 The Association for the Study of Animal
      Behaviour Copyright 1998 The Association for the Study of Animal Behaviour.

PMID- 9514675
TI  - Intraspecific responses to distress calls of the pipistrelle bat, Pipistrellus
      pipistrellus
AB  - Responses of the vespertilionid bat Pipistrellus pipistrellus to five recently
      caught conspecifics confined to a wire-mesh cage, at distances of 50 and 5 m from
      their roosts, were recorded on 12 separate evenings at three roosts during
      pregnancy and lactation. When bats were confined 50 m from their roost, an almost
      20-fold increase in the number of bats that passed across an open site around the
      cage was recorded and the strength of response (number of bat passes) increased
      with time. When the bats were 5 m from the roost there was an 80-fold increase in
      bat activity above the cage. Playbacks of recorded distress calls produced by
      single hand-held bats resulted in a more than three-fold increase in bat passes,
      but the response waned rapidly. The distress calls of recently caught P.
      pipistrellus were generally similar to those of individuals from the same colony
      held for longer in captivity, and differences in distress calls between two of
      the three colonies studied probably reflect differences in the physiological
      states of recorded bats, rather than the existence of colony-specific
      vocalizations. Distress calls probably function in attracting conspecifics which
      perform mobbing behaviour as an anti-predator response. Copyright 1998 The
      Association for the Study of Animal Behaviour Copyright 1998 The Association for
      the Study of Animal Behaviour.

PMID- 9514676
TI  - Porcine sex ratios and sex combinations within litters: comment on Meikle et al.
      (1997) and Mendl et al. (1997)
AB  - No abstract. Copyright 1998 The Association for the Study of Animal Behaviour.

PMID- 9514677
TI  - Mechanisms of sex-ratio adjustment in domestic swine: reply to James
AB  - No abstract. Copyright 1998 The Association for the Study of Animal Behaviour.

PMID- 9514678
TI  - Multiple mechanisms may affect birth sex ratio in domestic pigs
AB  - No abstract. Copyright 1998 The Association for the Study of Animal Behaviour.

PMID- 9514679
TI  - The changing trade-off between food finding and food stealing in juvenile
      oystercatchers
AB  - When juvenile oystercatchers, Haematopus ostralegus, first arrived on the
      wintering grounds in August and September, they regularly stole mussels, Mytilus
      edulis, from other, mainly older, oystercatchers. By October, however, juveniles
      stole far fewer mussels and found almost all their mussels independently for
      themselves on the mussel bed. Although stealing a mussel was always less
      profitable than taking a mussel from the mussel bed, a simple rate-maximizing
      optimality model showed that, in August and September, juveniles increased both
      their net and gross rates of energy intake by stealing because they were rather
      inefficient at foraging for themselves. By October, their greater efficiency at
      finding good quality mussels, combined with the increased resistance of potential
      victims to kleptoparasitic attacks, resulted in higher intake rates if juveniles
      stopped stealing mussels and took mussels only from the mussel bed. Copyright
      1998 The Association for the Study of Animal Behaviour Copyright 1998 The
      Association for the Study of Animal Behaviour.

PMID- 9514680
TI  - Feeding interruptions, diurnal mass changes and daily routines of behaviour in
      the zebra finch
AB  - We investigated daily changes in body mass, fat reserves and crop contents, and
      diurnal organization of behaviour, in the zebra finch, Taeniopygia guttata, in
      relation to experimental manipulations of food availability. Diurnal mass change
      and the organization of foraging behaviour during the day were in general
      agreement with recent theoretical predictions. Foraging intensity, and hence rate
      of mass gain, was most rapid immediately after dawn and before dusk. The
      experimental birds did not alter either mean body mass or their diurnal mass
      trajectory after a period of 2 weeks when food was made unavailable for 2 h a day
      at unpredictable times. Instead, they changed their allocation of time to
      different activities during the day, decreasing the mean amount of time spent
      locomoting and increasing the mean amount of time spent inactive over the day.
      Thus, contrary to a number of recent studies on different species, zebra finches
      appear to respond to unpredictable interruptions in food supply by reducing
      energetically expensive activities rather than adjusting their levels of energy
      reserves. Copyright 1998 The Association for the Study of Animal Behaviour
      Copyright 1998 The Association for the Study of Animal Behaviour.

PMID- 9514681
TI  - Male and female behaviour and extra-pair paternity in the wheatear
AB  - Behavioural observations and DNA fingerprinting were used to determine the
      relationship between male and female behaviours and levels of extra-pair
      paternity in the wheatear, Oenanthe oenanthe. Behavioural observations were
      consistent with the hypothesis that males attempted to ensure paternity by mate
      guarding, while pursuing extra-pair copulations (EPCs) primarily outside the
      fertile period of their pair female. The intensity of guarding varied with time
      of season and was greater at late nests. However, although males on territories
      with late nests also experienced high intrusion rates, the intensity of guarding
      was influenced more by the operational sex ratio (which was female skewed at
      early nests) than by intrusion rates per se. We suggest that early breeding males
      adopted a strategy of territorial defence to ensure paternity, as opposed to
      guarding their female directly (which late breeding males did), to capitalize on
      the increased opportunities to pursue EPCs in neighbouring territories. Females
      were less conspicuous than males in their pursuit of EPCs, were never seen off
      territory or observed to solicit extra-pair males directly, and rejected the
      majority of EPCs. The frequency of extra-pair paternity was 11% of 73 offspring,
      in 29% of 17 broods, and was not correlated with the intensity of guarding.
      Female cooperation appeared to be important for successful copulation, and extra
      pair paternity is therefore likely to be a consequence of solicited, or at least
      accepted, EPCs. We discuss why females might have participated in EPCs. Copyright
      1998 The Association for the Study of Animal Behaviour Copyright 1998 The
      Association for the Study of Animal Behaviour.

PMID- 9514682
TI  - Male parental effort and paternity in a variable mating system
AB  - Recent theoretical models suggest that males may respond to changes in paternity
      by adjusting their parental effort. Male response will depend on the availability
      of reliable paternity cues and the relative costs and benefits of parental effort
      to the male (i.e. its effect on the survival of young and alternative mating
      opportunities). Males breeding in pairs may be constrained because reductions in
      male parental effort are unlikely to be compensated for by the female and thus
      the survival of both related and unrelated young may decrease. In contrast, males
      breeding in cooperative groups (i.e. with helpers or co-breeders) may not have
      this constraint if other individuals in the group compensate for reductions in
      male parental effort. White-browed scrubwrens, Sericornis frontalis, breed in
      pairs and cooperative groups, typically with one female and two males (alpha and
      beta). We found that male parental effort was related positively to paternity for
      beta males, but not for alpha or pair males. Alpha males had paternity in all
      broods and always fed young. In contrast, beta males often had no paternity and
      sometimes did not feed young. Time spent near the fertile female was not an
      accurate predictor of the percentage of young sired in a brood, but it was a good
      predictor of having sired young in a brood. Our results are consistent with the
      idea that male parental effort is allocated according to whether or not the male
      copulated with the female. We suggest that the relationship between male parental
      effort and paternity may vary among cooperatively breeding species depending on
      the type and availability of cues to a male's paternity. Copyright 1998 The
      Association for the Study of Animal Behaviour Copyright 1998 The Association for
      the Study of Animal Behaviour.

PMID- 9514683
TI  - Consistency of female choice in the tungara frog: a permissive preference for
      complex characters
AB  - Previous phonotaxis experiments in the tungara frog, Physalaemus pustulosus,
      indicated a permissiveness in female preference that allows sexually selected
      complex call characters to be replaced with various alternative characters.
      Although they prefer complex to simple calls, females as a group did not
      discriminate between several alternative complex characters appended to the
      simple conspecific call. However, these studies did not address the possibility
      that the apparent permissiveness in female preference occurred because of an
      averaging of population data. The observed patterns in female preference could
      result from all females finding a certain set of call variants equally
      attractive, or from a polymorphism in female call preference. To discriminate
      between these two alternatives, consistency of mate choice was determined for
      three pairs of calls that elicited no phonotactic bias in population studies.
      Individual females did not repeatedly choose one stimulus of a pair over the
      other, demonstrating that the patterns of permissiveness observed in the
      population are paralleled by similar patterns within females. A broad preference
      for complex calls in the P. pustulosus species group would permit the evolution
      of sexually selected call variation through sensory exploitation. Copyright 1998
      The Association for the Study of Animal Behaviour Copyright 1998 The Association
      for the Study of Animal Behaviour.

PMID- 9514684
TI  - Spawning success in the damselfish Amblyglyphidodon leucogaster: the influence of
      eggs in the nest
AB  - Spawning success of males and its correlates were investigated in a natural
      colony of whitebelly damselfish, A. leucogaster (Pomacentridae), to explore the
      criteria that females use in choosing mates. The mating success of individual
      males was variable, with some males acquiring as few as 5000 eggs and others as
      many as 450 000 eggs during a breeding season. Male spawning success was not
      correlated with body size, territory size, nest site parameters or parental care
      behaviour. Egg hatching success was not related to either male size or egg clutch
      size, and all males were capable of rearing eggs to hatching. The temporal
      sequence of choices by females indicated non-independent choice by females, such
      that males chosen by females on the first spawn of the day were also chosen by
      females that spawned later in the day. Field observations indicated that, in the
      absence of male courtship, females preferentially visited males that had eggs in
      their nest site. Males that had recently mated were preferred by females over
      those males with either late-stage eggs or no eggs in the nest. This female
      preference did not appear to be related to increased paternal care or egg clutch
      survival. Given that the mating system is promiscuous and non-resource based, and
      that there appears to be little difference among males in body size, females may
      be mating non-independently by mimicking the choice of other females. Copyright
      1998 The Association for the Study of Animal Behaviour Copyright 1998 The
      Association for the Study of Animal Behaviour.

PMID- 9514685
TI  - Erratum
AB  - No abstract. Copyright 1998 The Association for the Study of Animal Behaviour.

PMID- 9514686
TI  - Cognitive Load and Learner Expertise: Split-Attention and Redundancy Effects in
      Reading with Explanatory Notes
AB  - Five experiments were conducted to examine the effects of cognitive load
      management using explanatory notes in reading passages for readers with different
      levels of expertise. Experiment 1 found that explanatory notes improved 5th
      grade, first-language learners' comprehension (high-level processing) but not
      vocabulary learning (low-level processing). Experiment 2 found that vocabulary
      definitions integrated within a passage (integrated format) enhanced 5th graders'
      comprehension compared to a separate vocabulary list (separated format) but
      reduced vocabulary learning. Experiment 3, using adult readers, found that an
      integrated format reduced comprehension but enhanced vocabulary learning.
      Experiment 4 used low-ability 8th-grade learners of English as a second language
      (ESL) and found an effect similar to the 5th graders in Experiment 2. Experiment
      5 showed that the effect for high-ability ESL learners was similar to the adults
      in Experiment 3. We argue that the efficiency of instruction depends on the
      extent to which it imposes an extraneous cognitive load. The same presentation
      format may facilitate performance or interfere with performance either through
      split-attention or redundancy effects, depending on learners' expertise.
      Copyright 1998 Academic Press.

PMID- 9514687
TI  - Three-Dimensional Representations of Contour Maps
AB  - Contour map learning may require three-dimensional representation of the area
      depicted by a contour map. The purpose of the study was to test the hypothesis
      that participants created three-dimensional mental representations of contour
      maps when asked to generate a cross-section profile of the map terrain from one
      point on the contour map to another. Gender differences in cross-section
      performance were also investigated, and it was hypothesized that males would
      perform better than females in a contour map cross-section test. Participants
      studied a series of contour maps or landsurface maps (three-dimensional drawings
      of an area), and answered two cross-section questions per map. Following the
      cross-section test, participants were given an incidental recognition test for
      the previously studied maps, either in a contour map format or a landsurface map
      format. Males recognized the landsurface maps corresponding to the contour map
      cross-section questions answered correctly better than contour map cross-section
      questions answered incorrectly, whereas females did not. This finding suggested
      that males, but not females, formed three-dimensional representations of the
      contour maps. There were no gender differences in performance on the contour map
      cross-section test, but males achieved higher recognition scores than females
      when the cross-section stimuli were contour maps. It was concluded that multiple
      spatial and verbal processing strategies can be used successfully to solve a
      contour map cross-section test, but that three-dimensional spatial processing may
      be more efficient than other forms of processing for long-term memory of contour
      maps. Copyright 1998 Academic Press.

PMID- 9514688
TI  - Self-Regulation Behaviors in Underprepared (Developmental) and Regular Admission
      College Students
AB  - Although there is evidence that self-regulated learning processes, such as self
      efficacy and goal setting, are significantly related to academic success most
      studies have not included participants from the one third of the entering college
      students who must take remedial college courses. The purpose of our research was
      to examine the differences between the self regulation reported by regular
      admission students and by underprepared students. We hypothesized that self
      regulating behaviors could predict developmental, that is underprepared, status
      or regular admission status among postsecondary students. Self regulation
      processes in randomly selected developmental and regular admission college
      students were identified using a structured interview. A discriminant function
      analysis tested the predictive ability of three measures of self regulating
      behavior. Developmental and regular admission students differed significantly in
      their self regulatory strategy deployment. The results suggest that self
      regulation may be a distinguishing characteristic between some developmental and
      regular admission students. Copyright 1998 Academic Press.

PMID- 9514689
TI  - Accessing Prior Knowledge to Remember Text: A Comparison of Advance Organizers
      and Maps
AB  - Two theories, schema and dual coding, and the conjoint retention model were
      contrasted to explain the role of geographic familiarity and prior knowledge in
      map-passage retention. One hundred, eighty-six college students listened to a
      passage taking place in either a familiar or unfamiliar geographic domain and
      viewed either a map or no map of either of the two geographic areas. One-third of
      each group received either a general or specific advance organizer of the passage
      topic, or no organizer at all. Results revealed that maps function to bridge what
      learners already know about an area and what they need to remember from a
      passage. However, prior knowledge of geography is activated by the geographic
      propositions contained in a passage, with or without a map. Thus, maps serve a
      mnemonic function of imagery, but learners' prior knowledge of the geography of
      the map's space mediates the value of the map. Learners are able to generate an
      image of the map themselves if there are locational markers in the passage, and
      the geography of those markers are familiar. Copyright 1998 Academic Press.

PMID- 9514690
TI  - Learning from Worked-Out Examples: The Effects of Example Variability and
      Elicited Self-Explanations
AB  - It was investigated to what extent example variability and the elicitation of
      sophisticated self-explanations foster the acquisition of transferable knowledge
      by learning from worked-out examples. In addition, it was asked whether the
      effects of these factors are moderated by the learners' levels of prior topic
      knowledge. To this end, we had 56 apprentices from a bank learn calculation of
      compound interest and real interest. They were randomly assigned to the four
      conditions of a 2 x 2-factorial design (factor 1: uniform vs. multiple examples;
      factor 2: spontaneous vs. elicited self-explanations). The learning results were
      measured by a post-test comprising near-transfer problems and far-transfer
      problems. It was found that the acquisition of transferable knowledge can be
      supported by eliciting self-explanations. In the case of near transfer,
      especially learners with low levels of prior topic knowledge profited from the
      elicitation procedure. On the whole, the findings underline the "causal"
      relevance of the quality of self-explanations for knowledge acquisition by
      learning from worked-out examples. The assumption that multiple examples foster
      transfer performance, at least when sophisticated self-explanations are elicited,
      was not supported. Copyright 1998 Academic Press.

PMID- 9514691
TI  - Call for Papers
AB  - Copyright

PMID- 9514693
TI  - The Two Nuclei in the Dikaryon of the Homobasidiomycete Coprinus cinereus Change
      Position after Each Conjugate Division
AB  - We constructed a common-AB diploid strain of Coprinus cinereus and mated this to
      a compatible haploid strain to construct a diploid-haploid dikaryon. We examined
      the positions of the diploid and haploid nuclei in the apical and subapical cells
      of the dikaryon by fluorescence microscopy and microfluorometry. In 60% of apical
      cells the leading nucleus (the nucleus proximal to the hyphal apex) was diploid
      and the second nucleus (the nucleus distal to the apex) was haploid, whereas in
      the remaining 40% of apical cells the order of the two nuclei was reversed. It
      was also observed that in 97% of hyphae examined the order of the diploid and
      haploid nuclei was reversed between the apical cell and the subapical cell. Based
      on these observations, we conclude that the two nuclei alternate in taking the
      leading and second positions in the apical cell at almost every conjugate
      division in the dikaryon. Copyright 1998 Academic Press.

PMID- 9514694
TI  - Microscopic and Ultrastructural Examination of Vegetative Incompatibility in
      Partial Diploids Heterozygous at het Loci in Neurospora crassa
AB  - Vegetative (or heterokaryon) incompatibility is often characterized by cell death
      after anastomosis. In Neurospora crassa, partial diploid strains heterozygous for
      a single heterokaryon incompatibility (het) gene are viable, but grow at a
      significantly inhibited rate. Strains heterozygous for het-6 or het-c were
      examined microscopically for evidence of cell death; approximately 15% of cells
      randomly distributed within such colonies were dead or dying. Electron microscopy
      revealed extensive organelle degradation and plasmolysis. Ultimately, the
      cytoplasm fragmented into small membrane-bound bodies. Hyphal regrowth into dying
      cells from adjacent healthy cells was common. Ultrastructure and cell size
      measurements indicated no differences in death processes between incompatibility
      caused by het-6 and het-c. Linear growth rate was the only measured parameter
      which correlated with the observed macroscopic differences in colony morphology
      between het genes. The ultrastructural changes in dying cells were consistent
      with descriptions of apoptosis in plants and animals. However, designating
      vegetative incompatibility as apoptosis is premature without further study.
      Copyright 1998 Academic Press.

PMID- 9514695
TI  - Blue Light Overrides Repression of Asexual Sporulation by Mating Type Genes in
      the Basidiomycete Coprinus cinereus
AB  - Monokaryotic mycelia of the homobasidiomycete Coprinus cinereus form asexual
      spores (oidia) constitutively in abundant numbers. Mycelia with mutations in both
      mating type loci (Amut Bmut homokaryons) also produce copious oidia but only when
      exposed to blue light. We used such an Amut Bmut homokaryon to define
      environmental and inherent factors that influence the light-induced oidiation
      process. We show that the Amut function causes repression of oidiation in the
      dark and that light overrides this effect. Similarly, compatible genes from
      different haplotypes of the A mating type locus repress sporulation in the dark
      and not in the light. Compatible products of the B mating type locus reduce the
      outcome of light on A-mediated repression but the mutated B function present in
      the Amut Bmut homokaryons is not effective. In dikaryons, the coordinated
      regulation of asexual sporulation by compatible A and B mating type genes results
      in moderate oidia production in light. Copyright 1998 Academic Press.

PMID- 9514696
TI  - Partial signaling by cytokines: cytokine regulation of cell cycle and Fas
      dependent, activation-induced death in CD4+ subsets.
AB  - Fas-dependent, activation-induced death (AID) of T cells has been implicated in
      the regulation of peripheral T cell populations. We have previously reported that
      IL-2 plays a unique role in regulating sensitivity to AID in primary CD4+ cells.
      In this report we have compared the capacity of IL-2, IL-4, and IL-7 to increase
      entry into cell cycle vs their capacity to increase sensitivity to AID. Our data
      indicate that IL-2 plays a unique role in the regulation of AID in both Th1 and
      Th2 subsets and that with a given AID stimulus, cell cycle progression is
      necessary, but not sufficient, for AID. Interestingly, induction of cell cycle
      entry and sensitivity to AID can be dissociated (partial signaling) not only with
      different cytokines, but even with point mutations in IL-2 itself. This provides
      the first evidence that cytokine variants or pharmacological agents that mimic
      their action will be useful in enhancing selective elements of pleiotropic
      cytokine actions.

PMID- 9514697
TI  - Functional analysis of four tetraspans, CD9, CD53, CD81, and CD82, suggests a
      common role in costimulation, cell adhesion, and migration: only CD9 upregulates
      HB-EGF activity.
AB  - Molecules of the tetraspan superfamily are engaged in multimolecular complexes
      containing other proteins such as beta 1 integrins and MHC antigens. Although
      their functions are not clear, they have been suggested to play a role in cell
      adhesion and migration, signal transduction, and costimulation. We have in this
      paper directly compared the functional properties of four tetraspans, CD9, CD53,
      CD81, and CD82. mAbs to any of these molecules were able to deliver a
      costimulatory signal for CD3-mediated activation of the T cell line Jurkat. CD82
      mAbs were the most efficient in triggering this effect. Moreover, engagement of
      CD9, CD81, and CD82 induced the homotypic aggregation of the megakaryocytic cell
      line HEL, and inhibited the migration of this cell line. Similar results were
      obtained with the preB cell line NALM-6 using the CD9 and CD81 mAbs. The CD81 mAb
      5A6 produced the strongest effects. Therefore, the tetraspans are recognized by
      mAbs which produce similar effects on the same cell lines. This is consistent
      with the tetraspans being included in large molecular complexes and possibly
      forming a tetraspan network (the tetraspan web). We also demonstrate that the
      tetraspans are likely to keep specific functional properties inside this network.
      Indeed, we have demonstrated that the human CD9 is able, like the monkey
      molecule, to upregulate the activity of the transmembrane precursor of heparin
      binding EGF as a receptor for the diphtheria toxin when cotransfected in murine
      LM cells. Neither CD81, nor CD82 had such activity. By using chimeric CD9/CD81
      molecules we demonstrate that this activity requires the second half of CD9,
      which contains the large extracellular loop, the fourth transmembrane region, and
      the last short cytoplasmic domain.

PMID- 9514698
TI  - Generation of stable CD4+ and CD8+ T cell lines from patients immunized with ras
      oncogene-derived peptides reflecting codon 12 mutations.
AB  - Previous studies have identified and characterized both murine in vivo and human
      in vitro T cell responses reflecting specific mutations in the ras proto
      oncogenes at codon 12, 13, or 61. In an attempt to determine whether peptide
      epitopes reflecting point mutations in the ras oncogenes are immunogenic in
      humans for the production of CD4+ and/or CD8+ T cell responses, a phase I
      clinical trial was initiated in metastatic carcinoma patients whose primary
      tumors harbor mutations in the K-ras proto-oncogenes at codon 12. The peptides
      used here as immunogens, which were administered in Detox adjuvant, spanned the
      ras sequence 5-17 and reflected the amino acid substitution of glycine (Gly) at
      position 12 to aspartic acid (Asp), cysteine (Cys), or valine (Val). Three of
      eight evaluable patients have demonstrated peptide-specific cell-mediated
      immunity, as determined by the production of T cell lines resulting from the
      vaccination. First, an antigen (Ag)-specific, major histocompatibility complex
      (MHC) class II (DP)-restricted CD4+ T cell line was established in vitro from
      postvaccination lymphocytes of a non-small cell lung carcinoma patient whose
      primary tumor contained a Cys12 mutation when cultured on the immunizing peptide.
      Moreover, CD4+ proliferation was inducible against the corresponding mutant K-ras
      protein, suggesting productive T cell receptor recognition of exogenously
      processed Ag. Second, an Ag-specific, MHC class I (HLA-A2)-restricted CD8+
      cytotoxic T lymphocyte (CTL) line was established in vitro from postvaccination
      lymphocytes of a colon carcinoma patient whose primary tumor contained an Asp12
      mutation. To that end, a 10-mer peptide, nested within the 13-mer immunizing
      peptide, was identified [i.e., ras5-14(Asp12)], which was shown to bind to HLA-A2
      and display specific functional capacity for expansion of the in vivo primed CD8+
      CTL precursors. Third, both Ag-specific, MHC class II (DQ)-restricted CD4+ and
      MHC class I-restricted (HLA-A2) CD8+ T cell lines were generated from a single
      patient with duodenal carcinoma whose primary tumor contained a Val12 mutation
      when cultured on the immunizing 13-mer peptide or a nested 10-mer peptide [i.e.,
      ras5-14(Val12)], respectively. Evidence is thus provided that vaccination with
      mutant ras oncogene peptides in adjuvant may induce specific anti-ras cellular
      immune responses, with no detectable cross-reactivity toward normal proto-ras
      sequences. Moreover, we have identified for the first time human HLA-A2
      restricted, CD8+ CTL epitopes reflecting specific point mutations in the K-ras
      oncogenes at codon 12 which, in concert with the activation of the CD4+ T cell
      response, may have important implications for both active and passive
      immunotherapies in selected cancer patients.

PMID- 9514699
TI  - Reductions in the activation of ERK and JNK are associated with decreased IL-2
      production in T cells from elderly humans stimulated by the TCR/CD3 complex and
      costimulatory signals.
AB  - T cells from elderly humans often display impaired IL-2 production, but the
      mechanisms are unknown. Because the activities of extracellular signal-regulated
      kinases (ERK) and c-Jun NH2-terminal kinases (JNK) are important for IL-2
      production, the current study evaluated if aberrancies in the expression and
      activation of ERK2 or JNK might underlie decreased IL-2 production by human T
      cells during aging. The present results show that diminished ERK2 and JNK
      catalytic activities were commonly detected in T cells from elderly humans
      stimulated with anti-CD3 mAb OKT3 plus PMA. These reductions did not represent
      temporal shifts in activation or altered expression of ERK2 or JNK. In addition,
      the reductions of ERK2 activation in stimulated T cells from elderly individuals
      were accompanied by decreased Raf-1 kinase activation and could be observed
      without coexisting impairments in JNK activation. Stimulation of ERK2 activation
      in elderly T cells correlated with IL-2 production and decreased ERK2 activation
      was consistently associated with reduced IL-2 production. Although the age
      related decreases in JNK activation were accompanied by reduced IL-2 production,
      substantial impairments of JNK activation were observed with diminished ERK2
      activation. Moreover, anti-CD3/PMA-stimulated T cells from elderly individuals
      that displayed normal JNK activation and impaired ERK2 activation continued to
      demonstrate reduced IL-2 production. These findings show that impairments in the
      activation of ERK2 and JNK can accompany decreased IL-2 production by T cells
      from elderly humans and further suggest that aberrancies in TCR/CD3-dependent
      activation of the Raf-1/MEK/ERK2 cascade may be rate-limiting for the full
      induction of IL-2.

PMID- 9514700
TI  - Androgens alter B cell development in normal male mice.
AB  - Castration of normal male mice leads to splenic enlargement and expansion of the
      B cell population. Since the spleen does not express receptors for androgens,
      these changes are most likely mediated by effects of androgens on other target
      organs. Two potential sites of androgen-mediated effects on B cells are evaluated
      in these studies: thymus and bone marrow. We first confirmed other findings
      indicating that castration of normal male mice results in expansion in the
      numbers of bone marrow B cells and then extended these observations by showing
      that these changes were reversible following androgen replacement. B cell
      expansion in castrate marrow and spleen was not altered by prior thymectomy,
      suggesting that thymic androgen receptors are not involved in the observed
      effects. Androgen receptors were found to be present in both immature B cells and
      marrow stromal cells by immunoblotting and ligand binding assays. The results
      suggest a direct modulatory role for androgens on B cells within the bone marrow
      compartment.

PMID- 9514701
TI  - CD30-regulated apoptosis in murine CD8 T cells after cessation of TCR signals.
AB  - A variety of culture systems have been developed to study mechanisms of
      activation-induced cell death in peripheral T lymphocytes either during the
      initial period after exposure to an activating stimulus or following repeated
      stimulation of activated T cells. In this study we describe a new culture model
      for the analysis of apoptosis after withdrawal of TCR signals from activated T
      cells. T cells activated by anti-CD3 antibodies for 48 h and then further
      cultured in the presence of IL-2 but absence of continued CD3/TCR stimulation
      underwent dramatic cell death approximately 4 days following removal of the TCR
      stimulus. Apoptotic cells generated in this protocol, unlike those produced by
      hyperstimulation, retained substantial levels of degraded DNA following fixation,
      consistent with death in the G0/G1 phase of the cell cycle. This "agonist
      withdrawal" cell death occurred largely within the CD8 T cell subset, with CD4
      cells showing lower levels of apoptosis. This form of cell death did not appear
      to be the result of IL-2 exhaustion, since repeated addition of IL-2 during the
      culture period did not significantly alter the number of apoptotic cells.
      Apoptosis induced by agonist withdrawal was not blocked by Fas antigen fusion
      protein or by anti-TNF alpha-neutralizing antibodies, suggesting a mechanism
      independent of Fas/FasL and TNF alpha/TNF-R interactions. Cell death was,
      however, significantly inhibited by treatment with a CD30 fusion protein. CD30
      was found to be transiently expressed on CD8 T cells immediately prior to death,
      with lower expression on CD4 cells, while CD30 ligand was found to be expressed
      most strongly by CD4 T cells. These results suggest a role for CD30 in regulating
      the onset of apoptosis in CD8 T cells after interruption of CD3/TCR.

PMID- 9514702
TI  - Regulatory cells generated by testicular tolerization to retinal S-antigen:
      possible involvement of IL-4, IL-10, and TGF-beta in the suppression of
      experimental autoimmune uveoretinitis.
AB  - Intratesticular injection of a retinal protein (S-antigen) into Lewis rats
      induces systemic immunotolerance (designated orchidic tolerance) and renders
      animals refractory to experimental autoimmune uveoretinitis (EAU) produced by S
      antigen immunization. We demonstrated in this work that the immunotolerance could
      be transferred to syngeneic naive rats by both CD4+ and CD8+ regulatory cells.
      Attempts were then made to characterize the cytokines involved in the
      immunosuppressive activity of these regulatory cells. Using the in vitro
      lymphoproliferation assay, the inhibitory effect of CD4+ cells on effector cells
      was found to be reversed by antibodies against IL-4 and IL-10 but not by anti-TGF
      beta antibody. IL-4 (IC50 = 1.6 ng/10(6) cells) and IL-10 (IC50 = 0.6 ng/10(6)
      cells) added to the assay medium were potent inhibitors of effector cell
      proliferation. Increased immunoreactivity and mRNA expression for IL-4 and IL-10
      was observed for CD4+ regulatory cells. The inhibitory effect of CD8+ regulatory
      cells was reversed by anti-TGF-beta antibody but not by antibodies against IL-4
      and IL-10. Compared with control CD8+ cells, CD8+ cells from tolerized rats
      demonstrated higher immunoreactivity for TGF-beta but did not show an enhanced
      expression of mRNA for TGF-beta. TGF-beta 1 and TGF-beta 2 added to effector
      cells showed dichotomous effects; both isoforms stimulated cell proliferation at
      2.5 ng/10(6) cells and inhibited at lower or higher concentrations. These results
      led us to conclude that IL-4 and IL-10 are important cytokines for the
      immunosuppressive effect of CD4+ regulatory cells generated in orchidic
      tolerance. TGF-beta is an important immunosuppressive cytokine for CD8+
      regulatory cells but further studies will determine whether other cytokines are
      also involved.

PMID- 9514703
TI  - Monoclonal antibodies against human dendritic cell-like peripheral blood
      monocytes activated by granulocyte/macrophage-colony-stimulating factor plus
      interleukin 4.
AB  - Human peripheral blood monocytes activated by GM-CSF plus IL-4 have recently been
      found to exhibit characteristics of putative dendritic cells (DC). These cytokine
      activated monocytes (CAM) may express novel activation Ag that contribute
      significantly to their antigen presentation potency. To examine that possibility,
      mAb specific for CAM were derived. Seven mAb that stained CAM but not unactivated
      monocytes and other peripheral blood mononuclear cell types were identified.
      Further screening with a panel of cell lines identified two CAM-specific mAb. The
      first mAb, 2.1D10, was found to be mannose-receptor specific. A second mAb,
      6.3B7, immunoprecipitated a 190-kDa Ag. It stained neither activated B cells nor
      the putative peripheral blood precursor DC population. Furthermore, 6.3B7 did not
      recognize determinants in asparagine-linked carbohydrate chains or in sialic acid
      containing structures. These mAb against CAM membrane proteins may provide new
      insights into the requirements for optimal antigen presentation by macrophages
      and other APC types.

PMID- 9514705
TI  - New shuttle vectors for the introduction of cloned DNA in Desulfovibrio.
AB  - The pBG1 replicon from the cryptic plasmid of Desulfovibrio desulfuricans G100A
      was inserted into pTZ18U derivatives to generate a new family of shuttle vectors.
      These plasmids are stable both in Escherichia coli and in Desulfovibrio, they
      present a large number of unique restriction sites, and colonies of recombinant
      clones can be identified by blue/white screening in E. coli. The pBMC, pBMK, and
      pBMS series carry the cat, npt, or strAB genes as selectable markers,
      respectively. The pBMC6, pBMK6, and pBMS6 plasmids can be introduced both in D.
      desulfuricans and in Desulfovibrio fructosovorans by electrotransformation, and
      the pBMC7, pBMK7, and pBMS7 plasmids contain additional mobilization functions
      which makes them suitable for conjugation.

PMID- 9514706
TI  - Conjugative transfer of RP4-oriT shuttle vectors from Escherichia coli to
      Clostridium perfringens.
AB  - A chromosomally integrated copy of the IncP plasmid RP4 was shown to mediate the
      conjugative transfer of shuttle plasmids containing an oriT site from Escherichia
      coli to the anaerobic pathogen Clostridium perfringens. Two versatile shuttle
      plasmids, pJIR1456 and pJIR1457, which will be invaluable for the introduction of
      cloned genes into C. perfringens, were constructed.

PMID- 9514707
TI  - Co-insertional replication is responsible for tandem multimer formation during
      plasmid integration into the Dictyostelium genome.
AB  - We investigated the establishment of integrating transformation vectors in the
      genome of Dictyostelium discoideum to gain insight into the formation of the
      plasmid insertions and to investigate the conditions that determine the number of
      plasmid copies present in such insertions. Transformation vectors conferring
      resistance to neomycin and/or blasticidin were introduced into the cell as a
      calcium phosphate coprecipitate or by electroporation. The integration of the
      plasmid DNA was based on either recombinational integration of plasmids or
      restriction enzyme-mediated integration. The genomic DNA of the resulting
      transformants was examined by Southern blot analysis of pulsed-field gels and by
      the recently published method of direct electroporation into Escherichia coli.
      The number of insertion sites was found to be dependent on the transformation
      method used, and the minimum number of plasmid copies per insertion site required
      for resistance depended on the type and the concentration of the selective drug.
      Cotransformation studies revealed a strictly homogeneous composition of vector
      multimers from any given insertion site. This suggests that multimers arise by co
      insertional replication of a single plasmid monomer, rather than by subsequent
      additional insertion events involving homologous recombination. The
      multimerization of the integrated vector only occurred when the insertion was
      established by homologous recombination. Moreover, the number of plasmid copies
      appeared to be random, was established at the time of the transformation, and did
      not change with subsequent alterations to the selection regime.

PMID- 9514708
TI  - Genetically engineered vaccines: an overview.
AB  - Despite the early success demonstrated with the hepatitis B vaccine, no other
      recombinant engineered vaccine has been approved for use in humans. It is
      unlikely that a recombinant vaccine will be developed to replace an existing
      licensed human vaccine with a proven record of safety and efficacy. This is due
      to the economic reality of making vaccines for human use. Genetically engineered
      subunit vaccines are more costly to manufacture than conventional vaccines, since
      the antigen must be purified to a higher standard than was demanded of older,
      conventional vaccines. Each vaccine must also be subjected to extensive testing
      and review by the FDA, as it would be considered a new product. This is costly to
      a company in terms of both time and money and is unnecessary if a licensed
      product is already on the market. Although recombinant subunit vaccines hold
      great promise, they do present some potential limitations. In addition to being
      less reactogenic, recombinant subunit vaccines have a tendency to be less
      immunogenic than their conventional counterparts. This can be attributed to these
      vaccines being held to a higher degree of purity than was traditionally done for
      an earlier generation of licensed subunit vaccines. Ironically, the contaminants
      often found in conventional subunit vaccines may have aided in the inflammatory
      process, which is essential for initiating a vigorous immune response. This
      potential problem may be overcome by employing one of the many new types of
      adjuvants that are becoming available for use in humans. Recombinant subunit
      vaccines may also suffer from being too well-defined, because they are composed
      of a single antigen. In contrast, conventional vaccines contain trace amounts of
      other antigens that may aid in conferring an immunity to infectious agents that
      is more solid than could be provided by a monovalent vaccine. This problem can be
      minimized, where necessary, by creating recombinant vaccines that are composed of
      multiple antigens from the same pathogen. These issues are less of a concern with
      a live attenuated vaccine, since these vaccines are less costly, require fewer
      steps to manufacture, and elicit long-lived immunity after only a single dose.
      Unfortunately, live vaccines carry a higher risk of vaccine-induced complications
      in recipients that make their use in highly developed, litiginous countries
      unlikely. In lesser developed countries, where the prevalence of disease and the
      need for effective vaccines outweighs the risk associated with their
      administration, live vaccines may play an important role in human health. This
      review has attempted to make the reader aware of some of the current approaches
      and issues that are associated with the development of these vaccines.
      Genetically engineered vaccines hold great promise for the future, but the
      potential of these vaccines to improve human and animal health has yet to be
      fully realized.

PMID- 9514709
TI  - Characterization of mutants of the 6'-N-acetyltransferase encoded by the
      multiresistance transposon Tn1331: effect of Phen171-to-Leu171 and Tyr80-to-Cys80
      substitutions.
AB  - The Klebsiella pneumoniae plasmid pJHCMW1 harbors a copy of Tn1331, a
      multiresistance transposon that includes the aac(6')-Ib gene which encodes a 6'-N
      aminoglycoside acetyltransferase. This gene was mutagenized using the mutator
      Escherichia coli XL1-Red. Two plasmids with a single nucleotide mutation in
      aac(6')-Ib were selected for further analysis: pDP1 and pDP6. Plasmid pDP1 codes
      for a mutant enzyme, AAC(6')-IbDP1, that has the Phe171 replaced by a Leu
      residue. This mutant derivative showed a lower specific activity than the wild
      type enzyme when either kanamycin (Km) or its semisynthetic derivative amikacin
      (Ak) were used as substrates in enzymatic assays performed at 30 degrees C.
      Furthermore, AAC(6')-IbDP1 showed a change of specificity of substrate when
      incubated at 42 degrees C. While its acetylating activity for Km was higher at
      this temperature than at 30 degrees C, it had its ability to utilize Ak as
      substrate for acetylation considerably reduced. Accordingly, minimal inhibitory
      concentration assays showed that E. coli(pDP1) was resistant to Ak at 37 degrees
      C but susceptible at 42 degrees C. The same assays showed that E. coli(pDP1) was
      highly resistant to Km at either 37 degrees C or 42 degrees C. A high level of
      resistance to Ak was observed for E. coli(pJHCMW1) which harbors the wild-type
      AAC(6')-Ib at either 37 or 42 degrees C. Extension of the analyses to other
      aminoglycosides showed that the enzymatic activity of AAC(6')-IbDP1 as well as
      the E. coli(pDP1) MICs for netilmicin dropped at 42 degrees C as was the case for
      Ak. These results could indicate that at 42 degrees C the mutant adopts a
      conformation that makes it unable to efficiently acetylate aminoglycoside
      molecules substituted in the C-1amino group of the deoxystreptamine moiety.
      Plasmid pDP6 encodes the mutant AAC(6')-IbDP6 which has the Tyr80 substituted by
      a Cys residue. E. coli(pDP6) exhibited reduced MICs for Ak, Km, tobramycin, and
      netilmicin. Analysis of the acetylating activity of AAC(6')-IbDP6 showed only
      marginal levels of activity when either Ak, Km, tobramycin, or netilmicin were
      used as substrates.

PMID- 9514710
TI  - A novel plasmid pIJB1 possessing a putative 2,4-dichlorophenoxyacetate
      degradative transposon Tn5530 in Burkholderia cepacia strain 2a.
AB  - A 102-kb plasmid, pIJB1, was isolated from Burkholderia cepacia strain 2a, which
      is able to use 2,4-dichlorophenoxyacetate (2,4-D) as a sole carbon source, and a
      physical map of the plasmid has been established. It was observed that
      spontaneous loss of a 37-kb fragment of the plasmid after growth in nonselective
      medium occurred, generating a plasmid of diminished size, pIJB2. The deletion
      event is concomitant with the loss of the 2,4-D dissimilatory phenotype,
      indicating that at least some of the 2,4-D degradative genes are on the missing
      fragment. The missing fragment is flanked by two identical 4.3-kb insertion
      sequences (IS) and shows a typical composite transposon structure of 41-kb in
      size, designated Tn5530. The mutant plasmid pIJB2 possesses a single copy of the
      IS element.

PMID- 9514711
TI  - A 3.3-kb plasmid of enterohemorrhagic Escherichia coli O157:H7 is closely related
      to the core region of the Salmonella typhimurium antibiotic resistance plasmid
      NTP16.
AB  - A restriction enzyme map was constructed of a 3.3-kb plasmid derived from
      enterohemorrhagic Escherichia coli O157:H7 strain 4821 using the enzymes SmaI,
      HpaI, FokI, HaeIII, StyI, RsaI, Bg/II, ClaI, and EcoRV. The molecular size of
      p4821 was 3307 bp, determined by nucleotide sequencing. Homology searches in the
      EMBL database library revealed that the nucleotide sequence of P4821 is similar
      (> 98%) to the core region of the antibiotic resistance plasmid NTP16 of
      Salmonella typhimurium strains. Nucleotide sequence analysis showed that p4821
      contains all the information necessary for its replication, stability, and
      mobilization. However, the lack of tra genes indicates that the plasmid is
      nonconjugative. A possible transposon insertion site was found in p4821 but two
      such sites were found at the boundaries between the core region and the
      antibiotic resistance encoding transposons in plasmid NTP16. Using a
      hybridization assay, we determined that of 50 E. coli O157:H7 strains isolated in
      1996 in Wurzburg, Germany from patients with diarrhea and hemolytic-uremic
      syndrome, 4 strains (8%) contained plasmid p4821-specific sequences.

PMID- 9514712
TI  - The bacterial cell cycle at Chorin: dramatic advances.

PMID- 9514713
TI  - Dynamic competition between alternative structures in viroid RNAs simulated by an
      RNA folding algorithm.
AB  - The folding pathways of viroid RNAs were studied using computer simulations by
      the genetic algorithm for RNA folding. The folding simulations were performed for
      PSTVd RNAs of both polarities, using the wild-type sequence and some previously
      known mutants with suggested changes in the stable or metastable structures. It
      is shown that metastable multihairpin foldings in the minus strand replicative
      intermediates are established due to the specific folding pathway that ensures
      the absence of the most stable rod-like structure. Simulations of the PSTVd minus
      strand folding during transcription reveal a metastable hairpin, formed in the
      left terminal domain region of the PSTVd. Despite high sequence variability, this
      hairpin is conserved in all known large viroids of both subgroups of PSTVd type,
      and is presumably necessary to guide the folding of the HPII hairpin which is
      functional in the minus strand. The folding simulations are able to demonstrate
      the changes in the balance between metastable and stable structures in mutant
      PSTVd RNAs. The stable rod-like structure of the circular viroid (+) RNA is also
      folded via a dynamic folding pathway. Furthermore, the simulations show that
      intermediate steps in the forced evolution of a shortened PSTVd replicon may be
      reconstructed by a mechanistic model of different folding pathway requirements in
      plus- and minus-strand RNAs. Thus the formation of viroid RNA structure strongly
      depends on dynamics of competition between alternative RNA structures. This also
      suggests that the replication efficiency of viroid sequences may be estimated by
      a simulation of the folding process.

PMID- 9514714
TI  - The Crystal Structure of Enoyl-CoA Hydratase Complexed with Octanoyl-CoA Reveals
      the Structural Adaptations Required for Binding of a Long Chain Fatty Acid-CoA
      Molecule
AB  - The structure of the hexameric rat mitochondrial enoyl-Coenzyme A (CoA)
      hydratase, co-crystallised with the inhibitor octanoyl-CoA, has been refined at a
      resolution of 2.4 A. Enoyl-CoA hydratase catalyses the hydration of 2,3
      unsaturated enoyl-CoA thioesters. In the crystal structure only four of the six
      active sites of the hexamer in the asymmetric unit are occupied with a ligand
      molecule, showing an unliganded and a liganded active site within the same
      crystal form. While the protein assembly and fold is identical to the previously
      solved acetoacetyl-CoA complex, differences are observed close to the fatty acid
      binding pocket due to the different nature of the ligands. The fatty acid tail of
      octanoyl-CoA is bound in an extended conformation. This is possible because a
      high B-factor loop, which separates in the acetoacetyl-CoA complex the binding
      pocket of the acetoacetyl-CoA fatty acid tail from the intertrimer space, has
      moved aside to allow binding of the longer octanoyl-CoA moiety. The movement of
      this loop opens a tunnel which traverses the complete subunit from the solvent
      space to the intertrimer space. The conformation of the catalytic residues is
      identical, in both structures as well as in the liganded and the unliganded
      active sites. In the unliganded active sites a water molecules is bound between
      the two catalytic glutamate, residues Glu144 and Glu164. After superposition of a
      liganded active site on an unliganded active site this water molecule is close to
      the carbon centre that becomes hydroxylated in the hydratase reaction. These
      findings support the idea that the active site is rigid and that the catalytic
      residues and the water molecule, as seen in the unliganded active site, are pre
      positioned for very efficient catalysis.Copyright 1998 Academic Press Limited

PMID- 9514715
TI  - New DNA sequence rules for high affinity binding to histone octamer and sequence
      directed nucleosome positioning.
AB  - DNA sequences that position nucleosomes are of increasing interest because of
      their relationship to gene regulation in vivo and because of their utility in
      studies of nucleosome structure and function in vitro. However, at present our
      understanding of the rules for DNA sequence-directed nucleosome positioning is
      fragmentary, and existing positioning sequences have many limitations. We carried
      out a SELEX experiment starting with a large pool of chemically synthetic random.
      DNA molecules to identify those individuals having the highest affinity for
      histone octamer. A set of highest-affinity molecules were selected, cloned, and
      sequenced, their affinities (free energies) for histone octamer in nucleosome
      reconstitution measured, and their ability to position nucleosomes in vitro
      assessed by native gel electrophoresis. The selected sequences have higher
      affinity than previously known natural or non-natural sequences, and have a
      correspondingly strong nucleosome positioning ability. A variety of analyses
      including Fourier transform, real-space correlation, and direct counting
      computations were carried out to assess non-random features in the selected
      sequences. The results reveal sequence rules that were already identified in
      earlier studies of natural nucleosomal DNA, together with a large set of new
      rules having even stronger statistical significance. Possible physical origins of
      the selected molecules' high affinities are discussed. The sequences isolated in
      this study should prove valuable for studies of chromatin structure and function
      in vitro and, potentially, for studies in vivo.

PMID- 9514716
TI  - Contributions of orientation and hydrogen bonding to catalysis in Asn229 mutants
      of thymidylate synthase.
AB  - We have determined structures of binary and ternary complexes of five Asn229
      variants of thymidylate synthase (TS) and related their structures to the kinetic
      constants measured previously. Asn229 forms two hydrogen bonds to the pyrimidine
      ring of the substrate 2'-deoxyuridine-5'-monophosphate (dUMP). These hydrogen
      bonds constrain the orientation of dUMP in binary complexes with dUMP, and in
      ternary complexes with dUMP and the TS cofactor, 5,10-methylene-5,6,7,8
      tetrahydrofolate. In N229 mutants, where these hydrogen bonds cannot be made,
      dUMP binds in a misoriented or more disordered fashion. Most N229 mutants exhibit
      no activity for the dehalogenation of 5-bromo-dUMP, which requires correct
      orientation of dUMP against Cys198. Since bound dUMP forms the binding surface
      against which the pterin ring of cofactor binds, misorientation of dUMP results
      in higher Km values for cofactor. At the same time, binding of the cofactor aids
      in ordering and positioning dUMP for catalysis. Hydrophobic mutants, such as
      N229I, favor an arrangement of solvent molecules and side-chains around the
      ligands similar to that in a proposed transition state for ternary complex
      formation in wild-type TS, and kcat values are similar to the wild-type value.
      Smaller, more hydrophilic mutants favor arrangements of the solvent and side
      chains surrounding the ligands that do not resemble the proposed transition
      state. These changes correspond to decreases in kcat of up to 2000-fold, with
      only modest increases in Km or Kd. These results are consistent with the proposal
      that the hydrogen-bonding network between water, dUMP and side-chains in the
      active-site cavity contributes to catalysis in TS. Asn229 has the unique ability
      to maintain this critical network, without sterically interfering with dUMP
      binding.

PMID- 9514717
TI  - The natural 6 S RNA found in Q beta-infected cells is derived from host and phage
      RNA.
AB  - The RNA of Escherichia coli infected with RNA bacteriophage Q beta was isolated
      and screened for replicable short-chained RNA. In contrast to earlier assumptions
      we show that (i) short-chained replicable RNA is a very minor part of the RNA
      synthesized in the infection cycle, and (ii) that the replicable RNA isolated
      from infected cells is derived from cellular RNA, in particular 23 S rRNA and 10
      Sa RNA, and from Q beta RNA itself. None of the many RNA species known from in
      vitro experiments was found. The RNA species isolated were all inefficient
      templates. No replicable RNA could be isolated from non-infected cells. Even in
      cells expressing high amounts of Q beta replicase very few RNA species could be
      isolated. RNA generated in vitro in template-free synthesis is therefore not
      derived from RNA species found in vivo, and replicable RNA found in vitro is
      generated by a mechanism fundamentally different from the one operating in vivo.

PMID- 9514718
TI  - A theoretical analysis of specificity of nucleic acid interactions with
      oligonucleotides and peptide nucleic acids (PNAs).
AB  - We treat theoretically the problem of the specificity of interaction between
      nucleic acid and an oligonucleotide, its analog or its mimic (such as peptide
      nucleic acid, or PNA). We consider simplest models with only essential details
      using numerical solutions of kinetic equations and the kinetic Monte Carlo
      method. In our first model, describing the formation of complementary duplex, we
      demonstrate anti-correlation between specificity and affinity for nucleic
      acid/oligonucleotide interaction. We analyze in detail one notable exception.
      Homopyrimidine PNAs exhibit very high affinity to DNA forming extraordinarily
      stable DNA/(PNA)2 triplexes with the complementary DNA strand. At the same time,
      such PNAs show remarkable sequence specificity of binding to duplex DNA. We
      formulate a theoretical model for the two-step process of PNA interaction with
      DNA. The calculations demonstrate that two-stage binding may secure both high
      affinity and very high specificity of PNA interaction with DNA. Our computer
      simulations define the range of parameter values in which high specificity is
      achieved. These findings are of great importance for numerous applications of PNA
      and for design of future drugs which specifically interact with DNA.

PMID- 9514719
TI  - Crystal structure of the lysozyme from bacteriophage lambda and its relationship
      with V and C-type lysozymes.
AB  - Like other lysozymes, the bacteriophage lambda lysozyme is involved in the
      digestion of bacterial walls. This enzyme is remarkable in that its mechanism of
      action is different from the classical lysozyme's mechanism. From the point of
      view of protein evolution, it shows features of lysozymes from different classes.
      The crystal structure of the enzyme in which all tryptophan residues have been
      replaced by aza-tryptophan has been solved by X-ray crystallography at 2.3 A
      using a combination of multiple isomorphous replacement, non-crystallographic
      symmetry averaging and density modification techniques. There are three molecules
      in the asymmetric unit. The characteristic structural elements of lysozymes are
      conserved: each molecule is organized in two domains connected by a helix and the
      essential catalytic residue (Glu19) is located in the depth of a cleft between
      the two domains. This cleft shows an open conformation in two of the independent
      molecules, while access to the cavity is much more restricted in the last one. A
      structural alignment with T4 lysozyme and hen egg white lysozyme allows us to
      superpose about 60 C alpha atoms with a rms distance close to 2 A. The best
      alignments concern the helix preceding the catalytic residue, some parts of the
      beta sheets and the helix joining the two domains. The results of sequence
      alignments with the V and C lysozymes, in which weak local similarities had been
      detected, are compared with the structural results.

PMID- 9514720
TI  - Linkage of protonation and anion binding to the folding of Sac7d.
AB  - The temperature, pH, and salt dependence of the folding of recombinant Sac7d from
      the hyperthermophile Sulfolobus acidocaldarius is mapped using multi-dimensional
      differential scanning calorimetry (DSC) and folding progress surfaces followed by
      circular dichroism. Linkage relations are derived to explain the observed
      dependencies, and it is shown that the data can be explained by the linkage of at
      least two protonation reactions and two anion binding sites to a two-state
      unfolding process. Circular dichroism spectra indicate that a native-like fold is
      stabilized at acid pH by anion binding. An apparent binding isotherm surface
      (folding progress versus pH and salt) is used to obtain intrinsic chloride
      binding constants as a function of pH for both sites. A saddle is predicted in
      the folding progress surface (progress versus temperature and pH) at low salt
      with a minimum near pH 2 and 20 degrees C with approximately 25% of the protein
      folded. The position of the saddle is sensitive to the intrinsic delta C degrees
      of unfolding and provides a third measure of delta C degrees independent of that
      obtained by a Kirchoff plot of DSC data and chemical denaturation. The observed
      enthalpy of unfolding approaches zero near the saddle making the unfolding
      largely invisible to DSC under these conditions. The linkage analysis
      demonstrates that the delta C degrees for unfolding obtained from a Kirchoff plot
      of DSC data should be distinguished from the intrinsic delta C degrees of
      unfolding. It is shown that the discrepancy between the free energy of unfolding
      for Sac7d obtained by DSC and that obtained by chemical denaturation may be
      explained by the linkage of protonation and anion binding to protein folding. The
      linkage analysis demonstrates the limitations of using the delta Hcal/ delta Hvh
      ratio an indication of two-state unfolding.

PMID- 9514721
TI  - The multi-domain structure of protein disulfide isomerase is essential for high
      catalytic efficiency.
AB  - Protein disulfide isomerase (PDI) catalyzes protein folding linked to disulfide
      bond formation in secreted proteins. It consists of four major domains, denoted
      a, b, b' and a'. The a and a' domains each contain an active site motif, -CGHC-,
      which is directly involved in thiol-disulfide exchange reactions during
      catalysis. The roles of the b and b' domains and the functional necessity for the
      multi-domain structure of PDI are unknown. We now demonstrate that full catalytic
      activity requires the involvement of multiple PDI domains and that the b' domain
      has a particularly important role in catalysis. Reconstruction of the PDI
      molecule from the isolated a and a' domains results in a progressive increase in
      catalytic efficiency as further domains are added. These effects are especially
      significant in the catalysis of disulfide bond rearrangements in folded
      substrates, for which all the domains of the protein are required for maximum
      catalytic efficiency. It is likely that all of the domains of PDI participate in
      substrate binding interactions and that PDI has evolved its multidomain structure
      as an adaptation that allows it to catalyze transformations involving difficult
      conformational changes.

PMID- 9514722
TI  - Refined crystal structure of methylamine dehydrogenase from Paracoccus
      denitrificans at 1.75 A resolution.
AB  - The three-dimensional structure of the quinoprotein methylamine dehydrogenase
      from Paracoccus denitrificans has been refined at 1.75 A resolution utilizing the
      DNA-based protein sequence. The final model incorporates 8034 atoms per molecule,
      including 552 molecules of solvent, and gives an R-factor of 0.163. The molecule
      is an H2L2 hetero-tetramer containing a non-crystallographic 2-fold axis of
      symmetry. The 373-residue H subunit is folded into seven repeats of a four
      stranded antiparallel beta-sheet motif, arranged in a propeller-like pattern
      about a pseudo-7-fold rotational axis of symmetry. Each L subunit contains 131
      residues folded in a tight structure composed of five beta-strands in two sheets
      and crosslinked by six disulfide bonds. In addition there is an intrasubunit
      covalent linkage between two tryptophan side-chains that form the unique redox
      center, tryptophan tryptophylquinone (TTQ). The active site contains the O-6
      carbonyl of TTQ, the side-chains of Asp32L Asp76L, Tyr119L and Thr122L, and two
      solvent molecules. A potential "gate" (Phe55H) separates the closed active-site
      cavity from a channel containing a group of highly ordered water molecules to
      bulk solvent. Phe55H and Tyr119L, and a number of neighboring oxygen atoms, may
      also provide a binding site for monovalent cations that are known to affect the
      reactivity and spectral properties of TTQ as well as the oxidative half reaction.
      The overall reaction has been dissected into a number of discrete steps that may
      require participation by several individual amino acid residues in the active
      site acting as general acids and bases.

PMID- 9514723
TI  - Kinetics of lysozyme refolding: structural characterization of a non-specifically
      collapsed state using time-resolved X-ray scattering.
AB  - We report time-resolved small angle X-ray scattering (SAXS) studies of the
      structural characteristics of the collapsed state of lysozyme from henegg white
      (HEL) obtained on initiating refolding by rapidly changing solvent conditions
      from 8 M to 1.1 M urea at pH 2.9. At this reduced pH the lifetime, of about one
      second, of the non-specifically collapsed ensemble is considerably prolonged
      relative to its value at pH 5.2. The SAXS studies are combined with time resolved
      measurements of tryptophan fluorescence and of the rate of formation of native
      molecules using interrupted refolding experiments. We observe large burst phase
      changes in intrinsic tryptophan fluorescence and in the radius of gyration (Rg)
      which is reduced from 22 A in the fully unfolded state to approximately 19 to 20
      A. Subsequent decrease of the Rg to the value for native lysozyme (15 A) follows
      the time course of formation of native molecules. Single exponential fits to the
      singular value decomposition (SVD) components of the SAXS data allow
      reconstruction of the SAXS profile at early time points of refolding. The results
      of this analysis suggest a globular shape of the collapsed state. A similar fit
      to the forward scattering amplitude, I(0), suggests that the collapsed state has
      a solvent accessible surface area which is considerably increased relative to
      that of the native protein. These results show directly that the non-specifically
      collapsed state formed during the burst phase in lysozyme refolding indeed
      represents a molecular compaction and a change in shape from a fully denatured
      random coil state (albeit restricted by disulfide bonds) to an ensemble of
      globular conformations which, however, have not yet formed a solvent-protected
      hydrophobic core.

PMID- 9514724
TI  - Measurement of the DNA bend angle induced by the catabolite activator protein
      using Monte Carlo simulation of cyclization kinetics.
AB  - A Monte Carlo simulation method for studying DNA cyclization (or ring-closure)
      has been extended to the case of protein-induced bending, and its application to
      experimental data has been demonstrated. Estimates for the geometric parameters
      describing the DNA bend induced by the catabolite activator protein (CAP or CRP)
      were obtained which correctly predict experimental DNA cyclization probabilities
      (J factors), determined for a set of 11 150 to 166 bp DNA restriction fragments
      bearing A tracts phased against CAP binding sites. We find that simulation of out
      of-phase molecules is difficult and time consuming, requiring the geometric
      parameters to be optimized individually rather than globally. A wedge angle model
      for DNA bending was found to make reasonable predictions for the free DNA. The
      bend angle in the CAP-DNA complex is estimated to be 85 to 90 degrees, in
      agreement with estimates from gel electrophoresis and X-ray co-crystal
      structures. Since the DNA is found to have a pre-existing bend of 15 degrees, the
      change in bend angle induced by CAP is 70 to 75 degrees, in a agreement with an
      estimate from topological measurements. We find evidence for slight
      (approximately 10 degrees) unwinding by CAP. The persistence length and helical
      repeat of the unbound portion of the DNA are in accord with literature-cited
      values, but the best-fit DNA torsional modulus C is found to be 1.7 (+/- 0.2) x
      10(-19) erg. cm, versus literature estimates and best-fit values for the free DNA
      of 2.0 x 10(-19) to 3.4 x 10(-19) erg.com. Simulations using this low value of C
      predict that cyclization of molecules with out-of-phase bends proceeds via
      undertwisting or overtwisting of the DNA between the bends, so as to align the
      bends, rather than through conformations with substantial writhe. We present
      experiments on the topoisomers formed by cyclization with CAP which support this
      conclusion, and thereby rationalize the surprising result that cyclization can
      actually be enhanced by out-of-phase bends if the twist required to align the
      bends improves the torsional alignment of the ends. The relationship between the
      present work and previous studies on DNA bending by CAP is discussed, and
      recommendations are given for the efficient application of the
      cyclization/simulation approach to DNA bending.

PMID- 9514725
TI  - Consistent structure between bacterial and mitochondrial NADH:ubiquinone
      oxidoreductase (complex I).
AB  - Respiratory chains of bacteria and mitochondria contain closely related forms of
      the proton-pumping NADH:ubiquinone oxidoreductase (complex I). In bacteria the
      complex has a molecular mass of approximately 530 kDa and consists of 14
      different subunits. The homologues of these 14 subunits together with some 27
      additional subunits make up the mitochondrial complex, adding up to a molecular
      mass of approximately 1 MDa. We calculated three-dimensional models at medium
      resolution of isolated and negatively stained complex I particles from Eschericha
      coli and Neurospora crassa by electron microscopy using the random conical tilt
      reconstruction technique. Both the bacterial and the mitochondrial complexes are
      L-shaped molecules with an intrinsic membrane arm extending into the lipid
      bilayer and a peripheral arm protruding from the membrane. It is discussed
      whether the consistent length of the arms of both complexes has an implication
      for their function. The additional protein mass of the mitochondrial complex is
      distributed along both arms, but especially around the junction between the two
      arms and around the membrane arm. It appears that the structural framework of
      procaryotic complex I is stabilized in eucaryotes by this additional mass. A
      discrete location of additional protein in the peripheral arm of the
      mitochondrial complex is interpreted as being the possible position of two
      subunits with a specialized role in the biosynthesis of a yet unknown cofactor of
      complex I.

PMID- 9514726
TI  - Rapid refinement of protein interfaces incorporating solvation: application to
      the docking problem.
AB  - A computationally tractable strategy has been developed to refine protein-protein
      interfaces that models the effects of side-chain conformational change, solvation
      and limited rigid-body movement of the subunits. The proteins are described at
      the atomic level by a multiple copy representation of side-chains modelled
      according to a rotamer library on a fixed peptide backbone. The surrounding
      solvent environment is described by "soft" sphere Langevin dipoles for water that
      interact with the protein via electrostatic, van der Waals and field-dependent
      hydrophobic terms. Energy refinement is based on a two-step process in which (1)
      a probability-based conformational matrix of the protein side-chains is refined
      iteratively by a mean field method. A side-chain interacts with the protein
      backbone and the probability-weighted average of the surrounding protein side
      chains and solvent molecules. The resultant protein conformations then undergo
      (2) rigid-body energy minimization to relax the protein interface. Steps (1) and
      (2) are repeated until convergence of the interaction energy. The influence of
      refinement on side-chain conformation starting from unbound conformations found
      improvement in the RMSD of side-chains in the interface of protease-inhibitor
      complexes, and shows that the method leads to an improvement in interface
      geometry. In terms of discriminating between docked structures, the refinement
      was applied to two classes of protein-protein complex: five protease-protein
      inhibitor and four antibody-antigen complexes. A large number of putative docked
      complexes have already been generated for the test systems using our rigid-body
      docking program, FTDOCK. They include geometries that closely resemble the
      crystal complex, and therefore act as a test for the refinement procedure. In the
      protease-inhibitors, geometries that resemble the crystal complex are ranked in
      the top four solutions for four out of five systems when solvation is included in
      the energy function, against a background of between 26 and 364 complexes in the
      data set. The results for the antibody-antigen complexes are not as encouraging,
      with only two of the four systems showing discrimination. It would appear that
      these results reflect the somewhat different binding mechanism dominant in the
      two types of protein-protein complex. Binding in the protease-inhibitors appears
      to be "lock and key" in nature. The fixed backbone and mobile side-chain
      representation provide a good model for binding. Movements in the backbone
      geometry of antigens on binding represent an "induced-fit" and provides more of a
      challenge for the model. Given the limitations of the conformational sampling,
      the ability of the energy function to discriminate between native and non-native
      states is encouraging. Development of the approach to include greater
      conformational sampling could lead to a more general solution to the protein
      docking problem.

PMID- 9514727
TI  - SH3 in muscles: solution structure of the SH3 domain from nebulin.
AB  - The huge modular protein nebulin is located in the thin filament of striated
      muscle in vertebrates and is thought to bind and stabilize F-actin. The C
      terminal part of human nebulin is anchored in the sarcomeric Z-disk and contains
      an SH3 domain, the first of such motifs to be identified in a myofibrillar
      protein. We have determined the nebulin SH3 sequence from several species and
      found it strikingly conserved. We have also shown that the SH3 transcripts are
      constitutively expressed in skeletal muscle tissues. As the first step towards a
      molecular understanding of nebulin's cellular role we have determined the three
      dimensional structure of the human nebulin SH3 domain in solution by nuclear
      magnetic resonance (NMR) spectroscopy and compared it with other known SH3
      structures. The nebulin SH3 domain has a well-defined structure in solution with
      a typical SH3 topology, consisting of a beta-sandwich of two triple-stranded,
      antiparallel beta-sheets arranged at right angles to each other and of a single
      turn of a 310-helix. An additional double-stranded antiparallel beta-sheet in the
      RT loop bends over the beta-sandwich. The derived structure reveals a remarkable
      similarity with a distinct subset of SH3 domains, especially in the structural
      features of the exposed hydrophobic patch that is thought to be the site of
      interaction with polyproline ligands. On the basis of this similarity, we have
      modelled the interaction with an appropriate polyproline ligand and attempted to
      delineate the characteristics of the physiological SH3-binding partner in the Z
      disk. Our results represent the first step in reconstructing the structure of
      nebulin and are expected to contribute to our understanding of nebulin's
      functional role in myofibrillar assembly.

PMID- 9514728
TI  - Prediction of splice sites in plant pre-mRNA from sequence properties.
AB  - Heterologous introns are often inaccurately or inefficiently processed in higher
      plants. The precise features that distinguish the process of pre-mRNA splicing in
      plants from splicing in yeast and mammals are unclear. One contributing factor is
      the prominent base compositional contrast between U-rich plant introns and
      flanking G + C-rich exons. Inclusion of this contrast factor in recently
      developed statistical methods for splice site prediction from sequence inspection
      significantly improved prediction accuracy. We applied the prediction tools to re
      analyze experimental data on splice site selection and splicing efficiency for
      native and more than 170 mutated plant introns. In almost all cases, the
      experimentally determined preferred sites correspond to the highest scoring sites
      predicted by the model. In native genes, about 90% of splice sites are the
      locally highest scoring sites within the bounds of the flanking exon and intron.
      We propose that, in most cases, local context (about 50 bases upstream and
      downstream from a potential intron end) is sufficient to account for intrinsic
      splice site strength, and that competition for transacting factors determines
      splice site selection in vivo. We suggest that computer-aided splice site
      prediction can be a powerful tool for experimental design and interpretation.

PMID- 9514730
TI  - Empirical statistical estimates for sequence similarity searches.
AB  - The FASTA package of sequence comparison programs has been modified to provide
      accurate statistical estimates for local sequence similarity scores with gaps.
      These estimates are derived using the extreme value distribution from the mean
      and variance of the local similarity scores of unrelated sequences after the
      scores have been corrected for the expected effect of library sequence length.
      This approach allows accurate estimates to be calculated for both FASTA and Smith
      Waterman similarity scores for protein/protein, DNA/DNA, and protein/translated
      DNA comparisons. The accuracy of the statistical estimates is summarized for 54
      protein families using FASTA and Smith-Waterman scores. Probability estimates
      calculated from the distribution of similarity scores are generally conservative,
      as are probabilities calculated using the Altschul-Gish lambda, kappa, and eta
      parameters. The performance of several alternative methods for correcting
      similarity scores for library-sequence length was evaluated using 54 protein
      superfamilies from the PIR39 database and 110 protein families from the
      Prosite/SwissProt rel. 34 database. Both regression-scaled and Altschul-Gish
      scaled scores perform significantly better than unscaled Smith-Waterman or FASTA
      similarity scores. When the Prosite/ SwissProt test set is used, regression
      scaled scores perform slightly better; when the PIR database is used, Altschul
      Gish scaled scores perform best. Thus, length-corrected similarity scores improve
      the sensitivity of database searches. Statistical parameters that are derived
      from the distribution of similarity scores from the thousands of unrelated
      sequences typically encountered in a database search provide accurate estimates
      of statistical significance that can be used to infer sequence homology.

PMID- 9514729
TI  - Solution structure of calmodulin-W-7 complex: the basis of diversity in molecular
      recognition.
AB  - The solution structure of calcium-bound calmodulin (CaM) complexed with an
      antagonist, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), has been
      determined by multidimensional NMR spectroscopy. The structure consists of one
      molecule of W-7 binding to each of the two domains of CaM. In each domain, the W
      7 chloronaphthalene ring interacts with four methionine methyl groups and other
      aliphatic or aromatic side-chains in a deep hydrophobic pocket, the site
      responsible for CaM binding to CaM-dependent enzymes such as myosin light chain
      kinases (MLCKs) and CaM kinase II. This competitive binding at the same site
      between W-7 and CaM-dependent enzymes suggests the mechanism by which W-7
      inhibits CaM to activate the enzymes. The orientation of the W-7 naphthalene ring
      in the N-terminal pocket is rotated approximately 40 degrees with respect to that
      in the C-terminal pocket. The W-7 ring orientation differs significantly from the
      Trp800 indole ring of smooth muscle MLCK bound to the C-terminal pocket and the
      phenothiazine ring of trifluoperazine bound to the N or C-terminal pocket. These
      comparative structural analyses demonstrate that the two hydrophobic pockets of
      CaM can accommodate a variety of bulky aromatic rings, which provides a plausible
      structural basis for the diversity in CaM-mediated molecular recognition.

PMID- 9514731
TI  - A symmetric-iterated multiple alignment of protein sequences.
AB  - A new symmetric-iterative method for multiple alignment of protein sequences is
      presented. The method can be described as a combination of motif finding and
      dynamic programming procedures. It uses each sequence as a standard to which all
      sequences are aligned based on the significant segment pair alignment (SSPA)
      protocol. Sequences are further matched using a reduced scoring threshold to
      provide fillers and extensions between highly significant segment pair matches.
      The method produces alignment blocks that accommodate indels and are separated by
      variable-length unaligned segments. Construction of consensus sequences is
      iterative, assigning greater weights to more distantly related sequences. A
      consensus sequence and various measures of conservation at each aligned position
      can be used for comparisons between protein families, for data base searches, and
      for analysis of functional and evolutionary features. The method is illustrated
      on the extended family of prokaryotic and eukaryotic RecA-like sequences. The
      RecA-like sequences reveal extended alignments among eubacterial RecA and
      separately among eukaryotic/archaebacterial Rad51/RadA. Eleven conserved blocks
      are common to both groups, two of them encompassing the ATP-binding A and B
      sites. Among the most conserved positions are glycine residues. For example, they
      occur twice as doublets putatively serving as hinge connections that provide
      opportunity for alternative structural conformations. Also several charged/polar
      residues are highly conserved, probably consequent upon the extensive
      intermonomer interactions in RecA/Rad51 filament formation and possibly relevant
      protein-protein and protein-nucleic acid interactions.

PMID- 9514732
TI  - Solution structure of the glycosylated second type 2 module of fibronectin.
AB  - Fibronectin is an extracellular matrix glycoprotein that plays a role in a number
      of physiological processes involving cell adhesion and migration. The modules of
      the fibronectin monomer are organized into proteolytically resistant domains that
      in isolation retain their affinity for various ligands. The tertiary structure of
      the glycosylated second type 2 module (2F2) from the gelatin-binding domain of
      fibronectin was determined by two-dimensional nuclear magnetic resonance
      spectroscopy and simulated annealing. The structure is well defined with an
      overall fold typical of F2 modules, showing two double-stranded antiparallel beta
      sheets and a partially solvent-exposed hydrophobic cluster. An N-terminal beta
      sheet, that was not present in previously determined F2 module structures, may be
      important for defining the relative orientation of adjacent F2 modules in
      fibronectin. This is the first three-dimensional structure of a glycosylated
      module of fibronectin, and provides insight into the possible role of the
      glycosylation in protein stability, protease resistance and modulation of
      collagen binding. Based on the structures of the isolated modules, models for the
      1F22F2 pair were generated by randomly changing the orientation of the linker
      peptide between the modules. The models suggest that the two putative collagen
      binding sites in the pair form discrete binding sites, rather than combining to
      form a single binding site.

PMID- 9514733
TI  - Evaluating atomic models of F-actin with an undecagold-tagged phalloidin
      derivative.
AB  - We have prepared an undecagold-tagged phalloidin derivative to determine this
      mushroom toxin's binding site and orientation within the F-actin filament by
      scanning transmission electron microscopy (STEM) and 3-D helical reconstruction.
      Remarkably, when stoichiometrically bound to F-actin, the undecagold moiety of
      the derivative could be directly visualized by STEM along the two half-staggered
      long-pitch helical strands of single filaments. Most importantly, the structural
      data obtained when combined with various biochemical constraints enabled us to
      critically evaluate two distinct atomic models of the F-actin filament (i.e. the
      Holmes-Lorenz versus the Schutt-Lindberg model). Taken together, our data are in
      excellent agreement with the Holmes-Lorenz model.

PMID- 9514734
TI  - Paromomycin binding induces a local conformational change in the A-site of 16 S
      rRNA.
AB  - Aminoglycoside antibiotics that bind to ribosomal RNA in the aminoacyl-tRNA site
      (A-site) cause misreading of the genetic code and inhibit translocation. An A
      site RNA oligonucleotide specifically binds to aminoglycoside antibiotics and the
      structure of the RNA-paromomycin complex was previously determined by nuclear
      magnetic resonance (NMR) spectroscopy. Here, the A-site RNA structure in its free
      form has been determined using heteronuclear NMR and compared to the structure of
      the paromomycin-RNA complex. As in the complex with paromomycin, the asymmetric
      internal loop is closed by a Watson-Crick base-pair (C1407.G1494) and by two non
      canonical base-pairs (U1406.U1495, A1408.A1493). A1492 stacks below A1493 and is
      intercalated between the upper and lower stems. The comparison of the free and
      bound conformations of the RNA shows that two universally conserved residues of
      the A site of 16 S rRNA, A1492 and A1493, are displaced towards the minor groove
      of the RNA helix in presence of antibiotic. These changes in the RNA conformation
      place the N1 positions of A1492 and A1493 on the minor groove side of the A-site
      RNA and suggest a mechanism of action of aminoglycosides on translation.

PMID- 9514735
TI  - Binding of neomycin-class aminoglycoside antibiotics to the A-site of 16 S rRNA.
AB  - Aminoglycoside antibiotics that bind to ribosomal RNA in the aminoacyl-tRNA site
      (A-site) cause misreading of the genetic code and inhibit translocation. We have
      recently solved the structure of an A-site RNA-paromomycin complex. The structure
      suggested that rings I and II, common to all aminoglycosides that bind to the A
      site, are the minimum motif for specific ribosome binding to affect translation.
      This hypothesis was tested biochemically and with a detailed comparative NMR
      study of interaction of the aminoglycosides paromomycin, neomycin, ribostamycin,
      and neamine with the A-site RNA. Our NMR data show that rings I and II of
      neomycin-class aminoglycosides are sufficient to confer specificity to the
      binding of the antibiotics to the model A-site RNA. Neomycin, paromomycin,
      ribostamycin and neamine bind in the major groove of the A-site RNA in a unique
      binding pocket formed by non-canonical base pairs and a bulged nucleotide.
      Similar NMR properties of the RNA and the diverse antibiotics within the
      different complexes formed with neomycin, paromomycin, ribostamycin and neamine
      suggest similar structures for these complexes.

PMID- 9514736
TI  - The solution structure of the complex of Lactobacillus casei dihydrofolate
      reductase with methotrexate.
AB  - We have determined the three-dimensional solution structure of the complex of
      Lactobacillus casei dihydrofolate reductase (18.3 kDa, 162 amino acid residues)
      formed with the anticancer drug methotrexate using 2531 distance, 361 dihedral
      angle and 48 hydrogen bond restraints obtained from analysis of multidimensional
      NMR spectra. Simulated annealing calculations produced a family of 21 structures
      fully consistent with the constraints. The structure has four alpha-helices and
      eight beta-strands with two other regions, comprising residues 11 to 14 and 126
      to 127, also interacting with each other in a beta-sheet manner. The methotrexate
      binding site is very well defined and the structure around its glutamate moiety
      was improved by including restraints reflecting the previously determined
      specific interactions between the glutamate alpha-carboxylate group with Arg57
      and the gamma-carboxylate group with His28. The overall fold of the binary
      complex in solution is very similar to that observed in the X-ray studies of the
      ternary complex of L. casei dihydrofolate reductase formed with methotrexate and
      NADPH (the structures of the binary and ternary complexes have a root-mean-square
      difference over the backbone atoms of 0.97 A). Thus no major conformational
      change takes place when NADPH binds to the binary complex. In the binary complex,
      the loop comprising residues 9 to 23 which forms part of the active site has been
      shown to be in the "closed" conformation as defined by M. R. Sawaya & J. Kraut,
      who considered the corresponding loops in crystal structures of complexes of
      dihydrofolate reductases from several organisms. Thus the absence of the NADPH
      does not result in the "occluded" form of the loop as seen in crystal studies of
      some other dihydrofolate reductases in the absence of coenzyme. Some regions of
      the structure in the binary complex which form interaction sites for NADPH are
      less well defined than other regions. However, in general terms, the NADPH
      binding site appears to be essentially pre-formed in the binary complex. This may
      contribute to the tighter binding of coenzyme in the presence of methotrexate.

PMID- 9514737
TI  - Refined structure of satellite tobacco mosaic virus at 1.8 A resolution.
AB  - The molecular structure of satellite tobacco mosaic virus (STMV) has been refined
      to 1.8 A resolution using X-ray diffraction data collected from crystals grown in
      microgravity. The final R value was 0.179 and Rfree was 0.184 for 219,086
      independent reflections. The final model of the asymmetric unit contained amino
      acid residues 13 to 159 of a coat protein monomer, 21 nucleotides, a sulfate ion,
      and 168 water molecules. The nucleotides were visualized as 30 helical segments
      of nine base-pairs with an additional base stacked at each 3' end, plus a "free"
      nucleotide, not belonging to the helical segments, but firmly bound by the
      protein. Sulfate ions are located exactly on 5-fold axes and each is coordinated
      by ten asparagine side-chains. Of the 10,080 structural waters, 168 per
      asymmetric unit, about 20% serve to bridge the macromolecular components at
      protein-protein and protein-nucleic acid interfaces. Binding of RNA to the
      protein involves some salt linkages, particularly to the phosphate of the free
      nucleotide, but the major contribution is from an intricate network of hydrogen
      bonds. There are numerous water molecules in the RNA-protein interface, many
      serving as intermediate hydrogen bond bridges. The sugar-phosphate backbone
      contributes most of the donors and acceptors for the RNA. The helical RNA
      conformation is nearest that of A form DNA. The central region of a helical
      segment is most extensively involved in contacts with protein, and exhibits low
      thermal parameters which increase dramatically toward the ends. The visible RNA
      represents approximately 59% of the total nucleic acid in the virion and is
      derived from the single-stranded genome, which has folded upon itself to form
      helical segments. Linking of the helices and the free nucleotides in a contiguous
      and efficient manner severely restricts the disposition of the remaining, unseen
      nucleic acid. Using the remaining nucleotides it is possible to fold the RNA
      according to motifs that provide a periodic distribution of RNA structural
      elements compatible with the icosahedrally symmetrical arrangement seen in the
      crystallographic structure. The intimate relationship between protein and nucleic
      acid in STMV suggests an assembly pathway based on the cooperative and
      coordinated co-condensation of RNA with capsid protein dimers.

PMID- 9514738
TI  - Mini-proinsulin and mini-IGF-I: homologous protein sequences encoding non
      homologous structures.
AB  - Protein minimization highlights essential determinants of structure and function.
      Minimal models of proinsulin and insulin-like growth factor I contain homologous
      A and B domains as single-chain analogues. Such models (designated mini
      proinsulin and mini-IGF-I) have attracted wide interest due to their native
      foldability but complete absence of biological activity. The crystal structure of
      mini-proinsulin, determined as a T3R3 hexamer, is similar to that of the native
      insulin hexamer. Here, we describe the solution structure of a monomeric mini
      proinsulin under physiologic conditions and compare this structure to that of the
      corresponding two-chain analogue. The two proteins each contain substitutions in
      the B-chain (HisB10-->Asp and ProB28-->Asp) designed to destabilize self
      association by electrostatic repulsion; the proteins differ by the presence or
      absence of a peptide bond between LysB29 and GlyA1. The structures are
      essentially identical, resembling in each case the T-state crystallographic
      protomer. Differences are observed near the site of cross-linking: the adjoining
      A1-A8 alpha-helix (variable among crystal structures) is less well-ordered in
      mini-proinsulin than in the two-chain variant. The single-chain analogue is not
      completely inactive: its affinity for the insulin receptor is 1500-fold lower
      than that of the two-chain analogue. Moreover, at saturating concentrations mini
      proinsulin retains the ability to stimulate lipogenesis in adipocytes (native
      biological potency). These results suggest that a change in the conformation of
      insulin, as tethered by the B29-A1 peptide bond, optimizes affinity but is not
      integral to the mechanism of transmembrane signaling. Surprisingly, the tertiary
      structure of mini-proinsulin differs from that of mini-IGF-I (main-chain rms
      deviation 4.5 A) despite strict conservation of non-polar residues in their
      respective hydrophobic cores (side-chain rms deviation 4.9 A). Three-dimensional
      profile scores suggest that the two structures each provide acceptable templates
      for threading of insulin-like sequences. Mini-proinsulin and mini-IGF-I thus
      provide examples of homologous protein sequences encoding non-homologous
      structures.

PMID- 9514739
TI  - Crystal structure of microbial superantigen staphylococcal enterotoxin B at 1.5 A
      resolution: implications for superantigen recognition by MHC class II molecules
      and T-cell receptors.
AB  - Staphylococcal enterotoxin B is a member of a family of toxins known as
      superantigens that activate a large number of T-cells (up to 20%) by cross
      linking MHC class II molecules with T-cell receptors in a Vbeta-restricted
      fashion. The crystal structure of staphylococcal enterotoxin B presented here has
      been determined at 1.5 A resolution, the highest resolution so far for a
      superantigen. The final model contains 1948 protein atoms and 177 water molecules
      and has excellent geometry with root-mean-square (rms) deviation of 0.007 A and
      1.73 degrees in bond lengths and bond angles, respectively. The overall fold is
      similar to that of other microbial superantigens, but as it lacks the zinc
      binding site found in other members of this family, such as staphylococcal
      enterotoxin A, C2 and D, this enterotoxin possesses only one MHC class II binding
      site. Comparison of the crystal structure of free SEB and in complex with an MHC
      class II molecule revealed no major changes in the MHC-binding site upon complex
      formation. However, a number of water molecules found in the free SEB may be
      displaced in the complex or contribute further to its stability. Detailed
      analysis of the TcR-binding site of SEB, SEA and SEC2 shows significant
      differences which may account for the ability of each superantigen to bind
      specific Vbeta sequences.

PMID- 9514740
TI  - Formation of the gap junction intercellular channel requires a 30 degree rotation
      for interdigitating two apposing connexons.
AB  - Intercellular communication via gap junction membrane channels cannot occur until
      two apposing hemichannels (connexons) meet and dock to form a sealed cell-cell
      conduit. In particular, an important question is how does the structure at the
      extracellular surface influence the molecular recognition of the two connexons.
      In this study, cryoelectron microscopy and computer modeling provide evidence
      that the formation of the gap junction intercellular channel requires a 30 degree
      rotation between hemichannels for proper docking. With this amount of rotation,
      the peaks (protrusions) on one connexon fit into the valleys of the apposed
      connexon in the 3-D model, which would make for an ionically tight interface
      necessary for a functional cell-cell channel. Docking appears to be governed by a
      "lock and key" mechanism via a simple interdigitation of the six protrusions from
      each connexon. This interdigitation increases significantly the contact surface
      area and potential number of hydrogen bonds or hydrophobic interactions and/or
      other attractive interactions. Having a larger surface area than if the surfaces
      were flat would explain the biochemical requirements for conditions characterized
      previously for splitting of channels into hemichannels. The docked connexons were
      computationally fitted into two gap junction structures, which further confirmed
      the interdigitated manner of docking.

PMID- 9514741
TI  - Crystal structure of human recombinant ornithine aminotransferase.
AB  - Ornithine aminotransferase (OAT), a pyridoxal-5'-phosphate dependent enzyme,
      catalyses the transfer of the delta-amino group of L-ornithine to 2-oxoglutarate,
      producing L-glutamate-gamma-semialdehyde, which spontaneously cyclizes to
      pyrroline-5-carboxylate, and L-glutamate. The crystal structure determination of
      human recombinant OAT is described in this paper. As a first step, the structure
      was determined at low resolution (6 A) by molecular replacement using the refined
      structure of dialkylglycine decarboxylase as a search model. Crystallographic
      phases were then refined and extended in a step-wise fashion to 2.5 A by cyclic
      averaging of the electron density corresponding to the three monomers within the
      asymmetric unit. Interpretation of the resulting map was straightforward and
      refinement of the model resulted in an R-factor of 17.1% (Rfree=24.3%). The
      success of the procedure demonstrates the power of real-space molecular averaging
      even with only threefold redundancy. The alpha6-hexameric molecule is a trimer of
      intimate dimers with a monomer-monomer interface of 5500 A2 per subunit. The
      three dimers are related by an approximate 3-fold screw axis with a translational
      component of 18 A. The monomer fold is that of a typical representative of
      subgroup 2 aminotransferases and very similar to those described for
      dialkylglycine decarboxylase from Pseudomonas cepacia and glutamate-1
      semialdehyde aminomutase from Synechococcus. It consists of a large domain that
      contributes most to the subunit interface, a C-terminal small domain most distant
      to the 2-fold axis and an N-terminal region that contains a helix, a loop and a
      three stranded beta-meander embracing a protrusion in the large domain of the
      second subunit of the dimer. The large domain contains the characteristic central
      seven-stranded beta-sheet (agfedbc) covered by eight helices in a typical
      alpha/beta fold. The cofactor pyridoxal-5'-phosphate is bound through a Schiff
      base to Lys292, located in the loop between strands f and g. The C-terminal
      domain includes a four-stranded antiparallel beta-sheet in contact with the large
      domain and three further helices at the far end of the subunit. The active sites
      of the dimer lie, about 25 A apart, at the subunit and domain interfaces. The
      conical entrances are on opposite sides of the dimer. In the active site, R180,
      E235 and R413 are probable substrate binding residues. Structure-based sequence
      comparisons with related transaminases in this work support that view. In
      patients suffering from gyrate atrophy, a recessive hereditary genetic disorder
      that can cause blindness in humans, ornithine aminotransferase activity is
      lacking. A large number of frameshift and point mutations in the ornithine
      aminotransferase gene have been identified in such patients. Possible effects of
      the various point mutations on the structural stability or the catalytic
      competence of the enzyme are discussed in light of the three-dimensional
      structure.

PMID- 9514742
TI  - Structural principles for the inhibition of the 3'-5' exonuclease activity of
      Escherichia coli DNA polymerase I by phosphorothioates.
AB  - A two-metal-ion catalytic mechanism has previously been proposed for several
      phosphoryl-transfer enzymes. In order to extend the structural basis of this
      mechanism, crystal structures of three single-stranded DNA substrates bound to
      the 3'-5' exonucleolytic active site of the large fragment of DNA polymerase I
      from Escherichia coli have been elucidated. The first is a 2.1 A resolution
      structure of a Michaelis complex between the large fragment (or Klenow fragment,
      KF) and a single-stranded DNA substrate, stabilized by low pH and flash-freezing.
      The positions and identities of the catalytic metal ions, a Zn2+ at site A and a
      Mg2+ at site B, have been clearly established. The structural and kinetic
      consequences of sulfur substitutions in the scissile phosphate have been
      explored. A complex with the Rp isomer of phosphorothioate DNA, refined at 2.2 A
      resolution, shows Zn2+ bound to both metal sites and a mispositioning of the
      substrate and attacking nucleophile. The complex with the Sp phosphorothioate at
      2. 3 A resolution reveals that metal ions do not bind in the active site, having
      been displaced by a bulky sulfur atom. Steady-state kinetic experiments show that
      catalyzed hydrolysis of the Rp isomer was reduced only about 15-fold, while no
      enzyme activity could be detected with the Sp phosphorothioate, consistent with
      the structural observations. Furthermore, Mn2+ could not rescue the activity of
      the exonuclease on the Sp phosphorothioate. Taken together, these studies confirm
      and extend the proposed two-metal-ion exonuclease mechanism and provide a
      structural context to explain the effects of sulfur substitutions on this and
      other phosphoryl-transfer enzymes. These experiments also suggest that the
      possibility of metal-ion exclusion be taken into account when interpreting the
      results of Mn2+ rescue experiments.

PMID- 9514743
TI  - Characterization of ARC, a divergent member of the AAA ATPase family from
      Rhodococcus erythropolis.
AB  - A gene encoding a AAA ATPase was discovered in the 5' region of the second operon
      of 20 S proteasome subunits in the nocardioform actinomycete Rhodococcus
      erythropolis NI86/21. The gene was cloned and expressed in Escherichia coli. The
      protein, ARC (AAA ATPase forming Ring-shaped Complexes), is a divergent member of
      the AAA family. The deduced product of the arc gene is 591 residues long (66
      kDa). The purified protein possesses a low, N-ethylmaleimide-sensitive ATPase
      activity and forms rings of six subunits, arranged symmetrically around a central
      opening or cavity. Two-dimensional crystals grown on lipid monolayers yielded
      images of the ATPase molecules in "end-on" orientation at 1.9 nm resolution.

PMID- 9514744
TI  - Homologous DNA pairing domain peptides of RecA protein: intrinsic propensity to
      form beta-structures and filaments.
AB  - The 20 amino acid residue peptides derived from RecA loop L2 have been shown to
      be the pairing domain of RecA. The peptides bind to ss- and dsDNA, unstack ssDNA,
      and pair the ssDNA to its homologous target in a duplex DNA. As shown by circular
      dichroism, upon binding to DNA the disordered peptides adopt a beta-structure
      conformation. Here we show that the conformational change of the peptide from
      random coil to beta-structure is important in binding ss- and dsDNA. The beta
      structure in the DNA pairing peptides can be induced by many environmental
      conditions such as high pH, high concentration, and non-micellar sodium dodecyl
      sulfate (6 mM). This behavior indicates an intrinsic property of these peptides
      to form a beta-structure. A beta-structure model for the loop L2 of RecA protein
      when bound to DNA is thus proposed. The fact that aromatic residues at the
      central position 203 strongly modulate the peptide binding to DNA and subsequent
      biochemical activities can be accounted for by the direct effect of the aromatic
      amino acids on the peptide conformational change. The DNA-pairing domain of RecA
      visualized by electron microscopy self-assembles into a filamentous structure
      like RecA. The relevance of such a peptide filamentous structure to the structure
      of RecA when bound to DNA is discussed.

PMID- 9514745
TI  - Endogenous reverse transcriptase assays reveal synergy between combinations of
      the M184V and other drug resistance-conferring mutations in interactions with
      nucleoside analog triphosphates.
AB  - Resistance of HIV-1 reverse transcriptase (RT) to nucleoside analogs (e.g. AZT,
      ddC and 3TC) is conferred by various amino acid substitutions or combinations
      thereof on the RT molecule. The M184V mutation, that confers high and low-level
      resistance to 3TC and ddC, respectively, can restore sensitivity to AZT when
      introduced into RT against a background of AZT-resistance. The K65R mutation,
      that confers low level resistance to both 3TC and ddC, can also restore
      sensitivity to AZT. This information is of potential utility in choosing
      combinations of anti-viral drugs for clinical use. To explore this subject
      further, we have used an endogenous RT reaction to study mutated viruses
      containing M184V alone or M184V combined with each of the K65R, E89G or both the
      M41L and T215Y substitutions. Endogenous assays possess the advantage of
      utilizing genomic RNA as template in a reaction mixture that includes each of
      tRNALys.3 and viral nucleocapsid protein, necessary for specific initiation of
      reverse transcription, as well as all other viral proteins that might impact on
      this process. We now show that viruses containing both M184V and K65R displayed
      synergistic resistance to 3TC triphosphate (3TCTP), while the same combination
      yielded the same level of resistance to ddC triphosphate (ddCTP) as that
      manifested by K65R alone. The combination of M184V and E89G displayed synergistic
      resistance against ddCTP but not 3TCTP, while viruses containing only E89G were
      highly resistant to 3TCTP and displayed low-level resistance to ddCTP. The
      results show that endogenous RT assays can reveal variable synergistic,
      antagonistic, or neutral effects in regard to drug sensitivity, depending on the
      presence of specific amino acid substitutions in RT itself.

PMID- 9514746
TI  - Highly conserved charge-pair networks in the mitochondrial carrier family.
AB  - Selection for regain-of-function mutations in the yeast ADP/ATP carrier AAC2 has
      revealed an unexpected series of charge-pairs. Four of the six amino acids
      involved are found in the mitochondrial energy transfer motifs used to define
      this family of proteins. As such, the results found with the ADP/ATP carrier may
      apply to the family as a whole. Mitochondrial carriers are built from three
      homologous domains, each with the conserved motif PX(D,E)XX(K,R). Neutralization
      of the conserved positive charges at K48, R152 or R252 in these motifs results in
      respiration defective yeast. Neutralization of the negative charges at D149 and
      D249 also make respiration defective yeast, though E45G or E45Q mutants are able
      to grow on glycerol. Regain of function occurs when a complementary charge is
      lost from another site in the molecule. This phenomenon has been observed
      independently eight times and thus is strong evidence for charge-pairs existing
      between the affected residues. Five different charge-pairs have been detected in
      the yeast AAC2 by this method and three more can be predicted based on homology
      between the domains. The highly conserved charge-pairs occurring within or
      between the three mitochondrial energy transfer signatures seem to be a critical
      feature of mitochondrial carrier structure, independent of the substrates
      transported. Conformational switching between alternative charge-pairs may
      constitute part of the basis for transport.

PMID- 9514747
TI  - Fold assembly of small proteins using monte carlo simulations driven by
      restraints derived from multiple sequence alignments.
AB  - The feasibility of predicting the global fold of small proteins by incorporating
      predicted secondary and tertiary restraints into ab initio folding simulations
      has been demonstrated on a test set comprised of 20 non-homologous proteins, of
      which one was a blind prediction of target 42 in the recent CASP2 contest. These
      proteins contain from 37 to 100 residues and represent all secondary structural
      classes and a representative variety of global topologies. Secondary structure
      restraints are provided by the PHD secondary structure prediction algorithm that
      incorporates multiple sequence information. Predicted tertiary restraints are
      derived from multiple sequence alignments via a two-step process. First, seed
      side-chain contacts are identified from correlated mutation analysis, and then a
      threading-based algorithm is used to expand the number of these seed contacts. A
      lattice-based reduced protein model and a folding algorithm designed to
      incorporate these predicted restraints is described. Depending upon fold
      complexity, it is possible to assemble native-like topologies whose coordinate
      root-mean-square deviation from native is between 3.0 A and 6.5 A. The requisite
      level of accuracy in side-chain contact map prediction can be roughly 25% on
      average, provided that about 60% of the contact predictions are correct within +/
      1 residue and 95% of the predictions are correct within +/-4 residues. Precision
      in tertiary contact prediction is more critical than absolute accuracy.
      Furthermore, only a subset of the tertiary contacts, on the order of 25% of the
      total, is sufficient for successful topology assembly. Overall, this study
      suggests that the use of restraints derived from multiple sequence alignments
      combined with a fold assembly algorithm holds considerable promise for the
      prediction of the global topology of small proteins.

PMID- 9514748
TI  - CIS elements and trans-acting factors required for minus strand DNA transfer
      during reverse transcription of the genomic RNA of murine leukemia virus.
AB  - During reverse transcription of the retroviral genomic RNA, two obligatory DNA
      strand transfers take place to synthesize the complete proviral DNA with two
      LTRs. We have previously shown that using an in vitro system made up of two viral
      RNAs mimicking the 5' and 3' regions of the retroviral genome, both nucleocapsid
      protein and the repeat (R) sequences were necessary for minus strong-stop cDNA
      (ss-cDNA) transfer and elongation by reverse transcriptase (RT). In this paper we
      show that the basic residues of nucleocapsid protein NCp10 of Moloney murine
      leukemia virus (MoMuLV), but not the zinc finger, are necessary for minus strand
      transfer. In order to examine the role of the R sequence repeated at the 5' and
      3' ends of the genome in minus strand DNA transfer, the MoMuLV R sequence of 68
      nt was replaced by either HIV-1 R of 96 nt, or RSV R of 21 nt, or by an
      artificial sequence of 21 nt. Analysis of MoMuLV DNA strand transfer from the 5'
      RNA to the 3' RNA and elongation in the presence of NCp10 and RT showed that it
      was high with control MoMuLV R, high with RSV R, reduced with HIV-1 R, and
      undetectable with the artificial R sequence. These results suggest that minus
      strand DNA transfer is a process more complex than simple hybridization of ss
      cDNA to the 3' R sequence of the genomic RNA.

PMID- 9514749
TI  - Signal transduction and bacterial conjugation: characterization of the role of
      ArcA in regulating conjugative transfer of the resistance plasmid R1.
AB  - The role of the two-component response regulator ArcA protein in the transfer of
      the conjugative resistance plasmid R1 was investigated using a variety of in vivo
      and in vitro assays. The frequency of conjugal DNA transfer of plasmid R1-16, a
      derepressed variant of R1, was reduced by four orders of magnitude in an
      Escherichia coli host with a mutation in the arcA gene. Measurements of mRNAs
      transcribed from key plasmid transfer genes revealed that the abundance of each
      of the mRNA species investigated was reduced significantly in an arcA background.
      Gene fusion studies with the R1 PY promoter, the major promoter of the transfer
      operon, and a lacZ reporter gene, indicated that arcA is required for maximal
      expression from this promoter. However, a stimulating effect of arcA could only
      be detected when the plasmid-specified positive regulator of the transfer genes,
      traJ, was present. Electrophoretic mobility shift assays were used to demonstrate
      specific binding of purified ArcA protein and a purified and phosphorylated
      oligohistidine-tagged ArcA (His6-ArcA) to a DNA fragment containing the PY
      promoter region. The binding of phosphorylated His6-ArcA to the PY promoter was
      further characterized by DNase I footprinting. The observed protection pattern
      was characteristic for ArcA acting as a transcriptional activator.

PMID- 9514750
TI  - Crystal structure of a catalytic-site mutant alpha-amylase from Bacillus subtilis
      complexed with maltopentaose.
AB  - The X-ray crystal structure of a catalytic-site mutant EQ208 [Glu208-->Gln] of
      alpha-amylase from Bacillus subtilis cocrystallized with maltopentaose (G5) and
      acarbose has been determined by multiple isomorphous replacement at 2.5 A
      resolution. Restrained crystallographic refinement has resulted in an R-factor of
      19.8% in the 7.0 to 2.5 A resolution range. EQ208 consists of three domains
      containing a (beta/alpha)8-barrel as observed in other alpha-amylases. Clear
      connected density corresponding to a pentasaccharide was observed, which was
      considered as the G5 molecule based on the high affinity of EQ208 for G5 that
      could replace pre-bound acarbose or a possible transglycosylation product of
      acarbose. The conformation around the third alpha-(1,4)-glucosidic bond makes a
      sharp turn, allowing the substrate to fit into the L-shaped cleft. Aromatic
      residues build the walls of the substrate binding cleft and leucine residues form
      the inner curvature of the cleft. The amide nitrogen of Gln208 forms a hydrogen
      bond with the glucosidic oxygen in the scissile bond between Glc3 and Glc4 (Glc1
      is the non-reducing end glucose residue of the substrate). This hydrogen-bonding
      manner may correspond to that of the protonated state of Glu208 in the initial
      kinetic complex between wild-type enzyme and substrate. The amide oxygen of
      Gln208 is anchored by two hydrogen bonds with Ala177 and a water molecule,
      assisting to make the amide proton point precisely to the place of the catalytic
      attack. The carboxyl oxygen atoms of the other catalytic-site residues Asp176 and
      Asp269 form hydrogen bonds with the oxygen atoms of Glc3. The carboxyl group of
      Asp176 has non-bonded contacts to the anomeric carbon atom and to the endocyclic
      oxygen atom of Glc3. These results suggest that Glu208 acts as a general acid and
      Asp176 as a general base. Glc3 forms seven hydrogen bonds with the surrounding
      protein groups and a stacking interaction with Tyr62, which is consistent with
      the fact that Glc3 has the lowest mean thermal factor of 13.2 A2 among the five
      sugar residues. Three calcium ions are found, one of which is positioned near the
      substrate binding site as found in other alpha-amylases and could contribute to
      stabilization of the structure of the active site.

PMID- 9514751
TI  - Structure of the glycosylphosphatidylinositol membrane anchor glycan of a class-2
      variant surface glycoprotein from Trypanosoma brucei.
AB  - The neutral glycan fraction of the glycosylphosphatidylinositol (GPI) membrane
      anchor of a class-2 variant surface glycoprotein (VSG) from Trypanosoma brucei
      was isolated following aqueous hydrogen fluoride dephosphorylation and nitrous
      acid deamination of the purified glycoprotein. The neutral glycans were
      fractionated by high-pH anion exchange chromatography and gel-filtration and six
      major glycan structures were solved by a combination of one and two-dimensional
      NMR, composition analysis, methylation linkage analysis and electrospray-mass
      spectrometry. The glycans were similar to those previously described for class-1
      VSGs, in that they contained the linear trimannosyl sequence Manalpha1-2Manalpha1
      6Man and a complex alpha-galactose branch of up to Galalpha1-2Galalpha1
      6(Galalpha1-2)Gal, but most also contained an additional galactose residue
      attached alpha1-2 to the non-reducing terminal mannose residue and about one
      third contained an additional galactose residue attached beta1-3 to the middle
      mannose residue. The additional complexity of the class-2 VSG GPI glycans is
      discussed in terms of a biosynthetic model that explains the full range of mature
      GPI structures that can be expressed on different VSG classes by the same
      trypanosome clone.

PMID- 9514752
TI  - Role of the human homolog of the yeast transcription factor SPT5 in HIV-1 Tat
      activation.
AB  - The transactivator protein Tat stimulates transcriptional elongation from the HIV
      1 LTR. One mechanism by which Tat increases HIV-1 transcription is by interacting
      with RNA polymerase II and TFIIH to increase phosphorylation of the polymerase C
      terminal domain. Recent studies indicate that specific elongation factors may
      also be required to modulate Tat function. Here, we used biochemical analysis and
      in vitro transcription assays to identify cellular factors required for Tat
      activation. This analysis resulted in the purification of a cellular factor Tat
      CT1 which is a human homolog of the yeast transcription factor SPT5.
      Immunodepletion of Tat-CTl from HeLa extract demonstrated that this factor was
      involved in transcriptional activation by Tat. However, the absence of this
      factor from HeLa extract did not prevent transcriptional activation by VP16.
      These findings are consistent with a model in which Tat-mediated effects on
      transcriptional elongation are mediated in part by the action of the human
      homolog of the yeast transcription factor SPT5.

PMID- 9514753
TI  - Differences between the thermal stabilities of the three triple-helical domains
      of type IX collagen.
AB  - Fibre-forming collagens in dilute solution show highly co-operative helix-coil
      transitions at temperatures that are remarkably close to the body temperature of
      the animal from which the collagen was extracted. This close correlation holds
      across animal Phyla and the transition temperatures, which range from 5 degrees C
      to 40 degrees C, are adjusted to suit by changing the primary structure,
      especially the concentration of the water-bridge-enhancing hydroxyproline
      residue. Fibril-forming collagens are thermally stabilised by fibrillogenesis,
      which causes a loss of random coil configurational entropy by intermolecular and
      intramolecular cross-linking and by spacial confinement of the molecule within
      the lattice of the fibre. But this mechanism cannot apply to the full length of
      the type IX collagen molecule, since its COL3 arm, according to current models,
      projects out from the stabilising influence of the type II fibre. In this paper
      we examine the thermal stability of the type IX collagen molecule and its three
      triple-helical domains, thereby demonstrating that the COL3 arm is much more
      stable than the rest of the molecule. At a scanning rate of 60 deg. C/h COL3
      exhibited an unfolding endotherm with a tmax at 49.0 degrees C, well above body
      temperature. Corresponding peak maxima for COL1 and COL2 were seen at 40.6
      degrees C and 39.6 degrees C, respectively. The sizes of the thermally labile
      units of COL1, COL2 and COL3, calculated from the measured activation enthalpies,
      were 24, 28 and 28 residues, respectively, much smaller than type I (65 residues)
      because of the relatively short lengths of triple helix to be unfolded. However,
      unlike type I collagen, no regions of the required size were found completely
      devoid of hydroxyproline. Consequently, the intrinsic stabilities of these
      thermally labile units were higher than that of type I with DeltaH updownarrow
      DeltaS updownarrow for COL1, COL2 and COL3 being, respectively, 385 K, 371 K and
      384 K, contrasting with the much lower 349 K of type I collagen. We therefore
      speculate that the increased thermal stability of the thermally labile units was
      caused by the presence of the water-bridge-enhancing residue, hydroxyproline.
      Finally the stabilisation of type IX collagen tissue is considered and an
      alternative structural organisation of the type IX molecule on the type II fibre
      is proposed.

PMID- 9514754
TI  - An endo-1,4-beta-xylanase-encoding gene from Agaricus bisporus is regulated by
      compost-specific factors.
AB  - Compost is the preferred substrate for growth of the edible fungus Agaricus
      bisporus. Utilization of compost requires the production of enzymes involved in
      degradation of lignocellulolytic components. For molecular characterization of
      these processes we are isolating the encoding genes. By applying heterologous
      screening techniques, we have cloned such a gene, which is specifically induced
      on compost encoding an endo-1,4-beta-xylanase (xlnA) belonging to glycosyl
      hydrolase family 10. The gene encodes a pre-protein of 333 amino acid residues
      with a predicted molecular mass of 34,946 for the mature protein. The open
      reading frame is interrupted by ten introns of which introns 5 and 6 are
      separated by an exon of only two base-pairs. High expression of the xlnA gene was
      observed in vegetative mycelium grown on sterilized compost while xlnA messengers
      were not detected in fruit bodies. Addition of glucose or xylose to compost
      repressed xlnA expression. When glucose-grown colonies were transferred to a
      medium containing cellulose, xylan or xylose as sole carbon source, the organism
      responded by expressing xlnA at a high level for a short period. Transfer from
      glucose to compost yielded a much stronger and constant xlnA induction. A similar
      pattern of expression was found for the cel3 gene encoding a cellulase,
      suggesting that these genes are induced by compost-specific factors rather than
      by the substrates they act upon. Antiserum raised against XLNA protein, which was
      heterologously expressed in Escherichia coli, detected, when the fungus was grown
      on compost, an extracellular protein of 33 kDa with endo-xylanase activity.

PMID- 9514755
TI  - Generation of ligand binding sites in T4 lysozyme by deficiency-creating
      substitutions.
AB  - Several variants of T4 lysozyme have been identified that sequester small organic
      ligands in cavities or clefts. To evaluate potential binding sites for non-polar
      molecules, we screened a number of hydrophobic large-to-small mutants for
      stabilization in the presence of benzene. In addition to Leu99-->Ala, binding was
      indicated for at least five other mutants. Variants Met102-->Ala and Leu133-
      >Gly, and a crevice mutant, Phe104-->Ala, were further characterized using X-ray
      crystallography and thermal denaturation. As predicted from the shape of the
      cavity in the benzene complex, mutant Leu133-->Gly also bound p-xylene. We
      attempted to enlarge the cavity of the Met102-->Ala mutant into a deep crevice
      through an additional substitution, but the double mutant failed to bind ligands
      because an adjacent helix rearranged into a non-helical structure, apparently due
      to the loss of packing interactions. In general, the protein structure contracted
      slightly to reduce the volume of the void created by truncating substitutions and
      expanded upon binding the non-polar ligand, with shifts similar to those
      resulting from the mutations.A polar molecule binding site was also created by
      truncating Arg95 to alanine. This creates a highly complementary buried polar
      environment that can be utilized as a specific "receptor" for a guanidinium ion.
      Our results suggest that creating a deficiency through truncating mutations of
      buried residues generates "binding potential" for ligands with characteristics
      similar to the deleted side-chain. Analysis of complex and apo crystal structures
      of binding and non-binding mutants suggests that ligand size and shape as well as
      protein flexibility and complementarity are all determinants of binding. Binding
      at non-polar sites is governed by hydrophobicity and steric interactions and is
      relatively permissive. Binding at a polar site is more restrictive and requires
      extensive complementarity between the ligand and the site.

PMID- 9514756
TI  - Co-localization of polar replication fork barriers and rRNA transcription
      terminators in mouse rDNA.
AB  - We investigated the replication of the region where transcription terminates in
      mouse rDNA. It contains a replication fork barrier (RFB) that behaves in a polar
      manner, arresting only replication forks moving in the direction opposite to
      transcription. This RFB consists of several closely spaced fork arrest sites that
      co-localize with the transcription terminator elements, known as Sal boxes. Sal
      boxes are the target for mTTF-I (murine transcription termination factor I).
      These results suggest that both termination of rRNA transcription and replication
      fork arrest may share cis-acting as well as trans-acting factors.

PMID- 9514757
TI  - An example of a protein ligand found by database mining: description of the
      docking method and its verification by a 2.3 A X-ray structure of a thrombin
      ligand complex.
AB  - A computer program (SANDOCK) has been developed for the automated docking of
      small ligands to a target protein. It uses a guided matching algorithm to fit
      ligand atoms into the protein binding pocket. The protein is described by a
      modified Lee-Richard's dotted surface with each dot coded by chemical property
      and accessibility. Orientations of the ligand in the active site are generated
      such that a chemical and a shape complementary between the ligand and the active
      site cavity have to be fulfilled. The generated fits are evaluated with scoring
      functions which account for van der Waals, hydrophobic and hydrogen bonding
      interactions. This newly developed docking program can efficiently screen very
      large databases in a reasonable time and has been used to successfully identify
      novel ligands. The X-ray structure of a thrombin-ligand complex predicted by
      SANDOCK is described. The ligand binds to thrombin with a Kd of 65 microM and has
      an rmsd of 0.7 A for all ligand atoms from the predicted binding mode by SANDOCK.

PMID- 9514759
TI  - The conformational equilibrium of human growth hormone.
AB  - The structural stability of recombinant human growth hormone (rhGH) has been
      studied by differential scanning calorimetry, circular dichroism and by following
      the tyrosine and histidine chemical shifts in the 1H NMR spectrum. These studies
      demonstrate that the folding/unfolding equilibrium of rhGH involves a partially
      folded dimeric intermediate. The formation of this dimeric intermediate is a
      reversible process. At acid pH (pH 3) the conformational equilibrium is
      reversible even at high protein concentrations (10 mg/ml). At neutral pH
      reversibility is observed only at low protein concentrations (<0.5 mg/ml). The
      free energy of this intermediate conformation is only approximately 3 kcal/mol
      apart from the native state indicating that the conformational equilibrium can be
      effectively modulated by changes in solvent composition or physical conditions.
      According to the spectroscopic and thermodynamic results, the formation of the
      dimeric intermediate occurs without a major loss in helical content and is driven
      by the formation of substantial hydrophobic contacts between two partially folded
      molecules. A thermodynamic model that accounts quantitatively for the
      experimental data has been developed. These studies demonstrate that partially
      folded conformations of certain proteins are able to form stoichiometric
      complexes, and that the formation of these complexes provide a significant source
      of stabilizing Gibbs energy for conformational states that, otherwise, will be
      characterized by extremely unfavorable free energies.

PMID- 9514758
TI  - The small heat-shock protein, alphaB-crystallin, has a variable quaternary
      structure.
AB  - alphaB-crystallin is a major structural protein in the lens that is found in a
      variety of other tissues and is associated with numerous neurological disorders.
      It is a member of the small heat-shock protein family and possesses chaperone
      like properties. Cryo-electron microscopy has been applied to analyze the
      quaternary structure of human recombinant alphaB-crystallin, which spontaneously
      forms roughly spherical multimers 8 to 18 nm in diameter. Class-sum images based
      on nearly 5000 alphaB-crystallin particles reveal the presence of a large central
      cavity, weak regions of density within the protein shell, and an asymmetric
      quaternary structure. The class-sum images are variable in size and shape, and
      are suggestive of snapshots of a conformationally flexible assembly. As gel
      filtration chromatography reveals a range of molecular masses (650 (+/-140) kDa)
      for the assembly, the class-sum images were further classified on the basis of
      total molecular mass. A reconstruction at approximately 4 nm resolution was
      calculated from the images assigned to 32 subunit (approximately 645 kDa)
      assemblies. Comparison of class-sum images with reprojections of the
      reconstruction indicates that the resolution is limited by the variable nature of
      the assembly. A three-dimensional variance map indicates significant structural
      divergence within the protein shell and on the outer surface of the particle.
      Some of the strong variance may correspond to the flexible, exposed C-terminal
      residues of the alphaB-crystallin monomers. The variable quaternary structure of
      alphaB-crystallin is consistent with the polydisperse size of the assembly and
      the previously observed subunit exchange between multimers. Thus, we propose that
      the monomer packing is variable, and that the quaternary structure of the
      assembly is not completely defined. A variable alphaB-crystallin quaternary
      structure may facilitate binding of target proteins in up to stoichiometric
      ratios.

PMID- 9514760
TI  - Site-directed mutations in motif VI of Escherichia coli DNA helicase II result in
      multiple biochemical defects: evidence for the involvement of motif VI in the
      coupling of ATPase and DNA binding activities via conformational changes.
AB  - Two site-directed mutants of Escherichia coli DNA helicase II (UvrD) were
      constructed to examine the functional significance of motif VI in a superfamily I
      helicase. Threonine 604 and arginine 605, representing two of the most highly
      conserved residues in motif VI, were replaced with alanine, generating the mutant
      alleles uvrD-T604A and uvrD-R605A. Genetic complementation studies indicated that
      UvrD-T604A, but not UvrD-R605A, functioned in methyl-directed mismatch repair and
      UvrABC-mediated nucleotide excision repair. Both mutant enzymes were purified and
      single-stranded DNA (ssDNA)-stimulated ATP hydrolysis, duplex DNA unwinding, and
      ssDNA binding were studied in the steady-state and compared to wild-type UvrD.
      UvrD-T604A exhibited a serious defect in ssDNA binding in the absence of
      nucleotide. However, in the presence of a non-hydrolyzable ATP analog, DNA
      binding was only slightly compromised. Limited proteolysis experiments suggested
      that UvrD-T604A had a "looser" conformation and could not undergo conformational
      changes normally associated with ATP binding/hydrolysis and DNA binding. UvrD
      R605A, on the other hand, exhibited nearly normal DNA binding but had a severe
      defect in ATP hydrolysis (kcat=0.063 s-1 compared to 162 s-1 for UvrD). UvrD
      T604A exhibited a much less severe decrease in ATPase activity (kcat=8.8 s-1).
      The Km for ATP for both mutants was not significantly changed. The results
      suggest that residues within motif VI of helicase II are essential for multiple
      biochemical properties associated with the enzyme and that motif VI is
      potentially involved in conformational changes related to the coupling of ATPase
      and DNA binding activities.

PMID- 9514761
TI  - Membrane-induced alterations in HIV-1 Gag and matrix protein-protein
      interactions.
AB  - The matrix (MA) domain of human immunodeficiency virus type 1 (HIV-1) contains
      sequences that direct association with the nucleus at early times in the virus
      replication cycle and with the plasma membrane at late times in the cycle.
      Localization to these sites is critical for functions related to the
      establishment of the infecting provirus and viral assembly, respectively.
      Mutational and structural analyses indicate that the opposing targeting signals
      which mediate these subcellular localization events include the same basic
      residues found in the N-terminal region of the protein. Here, we examined protein
      multimerization as a determinant of membrane association. Under high ionic
      strength conditions, Gag, but not MA, binds phospholipid membranes with high
      affinity. The oligomerization state of the protein per se did not appear to be a
      prerequisite for stable membrane binding, as Gag and MA were both capable of
      forming oligomers in high ionic strength buffer. To determine the fate of Gag and
      MA multimers in the presence of phospholipid membranes in real time, we measured
      resonance energy transfer between oligomer subunits in the presence and absence
      of lipid. The presence of phospholipid significantly increased the efficiency of
      resonance energy transfer between Gag molecules, consistent with enhanced Gag
      multimerization. This suggests that Gag oligomers assembled on the membrane
      surface and correlated with the observed stability of membrane binding. In
      contrast, the efficiency of resonance energy transfer between MA molecules
      decreased, indicating that MA oligomers dissociated in the presence of membrane,
      consistent with observed unstable binding. Identical results were obtained
      whether the probes were covalently attached to a Lys residue in Gag or to
      residues specifically within the MA domain of Gag; whether the fluorophore was
      rhodamine or fluorescein; or whether hetero- or homotransfer was measured. The
      results suggest that phospholipid induces alterations in Gag and MA protein
      protein interactions that may contribute to the puzzling ability of MA to direct
      targeting functions requiring alternately membrane binding and membrane
      dissociation. The results also suggest that regions downstream of the MA domain
      in the precursor, or conformations formed after maturation of MA, play a critical
      role in oligomerization-modulated membrane binding.

PMID- 9514762
TI  - Thinking about a nuclear matrix.
AB  - The possible existence in eukaryotic cells of an internal, non-chromatin nuclear
      structural framework that facilitates gene readout as a set of spatially
      concerted reactions has become a popular but controversial theater of
      investigation. This article endeavors to present a circumspect review of the
      nuclear matrix concept as we presently know it, framed around two contrasting
      hypotheses: (1) that an internal nuclear framework actively enhances gene
      expression (in much the same way the cytoskeleton mediates cell locomotion,
      mitosis and intracellular vesicular traffic) versus (2) that the interphase
      chromosomes have fixed, inherited positions and that the DNA replication,
      transcripton and RNA processing machinery diffusionally arrives at sites of gene
      readout, with some aspects of nuclear structure thus being more a result than a
      cause of gene expression. On balance, the available information suggests that
      interactions among various gene expression machines may contribute to isolated
      nuclear matrix preparations. Some components of isolated nuclear matrix
      preparations may also reflect induced or reconfigured protein-protein
      associations. The protein characterization and ultrastructural analysis of the
      isolated nuclear matrix has advanced significantly in recent years, although
      controversies remain. Important new clues are now coming in from promising
      contemporary lines of research that report on nuclear structure in living cells.

PMID- 9514763
TI  - Small binding proteins selected from a combinatorial repertoire of knottins
      displayed on phage.
AB  - Knottins are a group of small, disulphide-bonded proteins that bind with high
      specificity to their target molecules. These proteins appear to use different
      faces of the protein for their interactions with different targets. Here, we
      attempted to create knottins with novel binding activities based on the cellulose
      binding domain of the fungal enzyme cellobiohydrolase I. Variation was introduced
      to the face of the protein that binds cellulose. Seven residues, which are
      located in two regions of the polypeptide chain and form a patch of about 400 A2
      on the protein surface, were simultaneously varied by random mutation of the
      gene. The repertoire was cloned for display on filamentous bacteriophage (5.5 x
      10(8) clones), and selected for binding to cellulose or to one of three enzymes
      (alpha-amylase, alkaline phosphatase and beta-glucuronidase). We thereby isolated
      variant knottins against cellulose (differing in sequence from the parent
      knottin) and also against alkaline phosphatase. The binding to (glycosylated)
      alkaline phosphatase was highly specific with an affinity of about 10 microM,
      required the presence of disulphide bonds and was mediated through protein
      (rather than carbohydrate) contacts. Knottin scaffolds therefore appear to be a
      promising architecture for the creation of small folded proteins with binding
      activities, with the potential for improvement of binding affinities by mutation,
      or of using other faces of the protein to provide greater structural diversity in
      the primary repertoire.

PMID- 9514765
TI  - Missense mutations that inactivate Escherichia coli lac permease.
AB  - Although missense mutations that inactivate integral membrane proteins cause a
      variety of diseases, the mechanisms by which they act are poorly understood. To
      establish a model for investigating this issue, we identified 51 missense
      mutations arising in vivo that inactivate Escherichia coli lac permease, a well
      characterized membrane transport protein. The mutants were isolated using a
      genetic screening procedure which eliminates mutations that block expression of
      the lac permease gene, such as nonsense and frameshift mutations. The majority of
      the 51 missense mutations caused highly non-conservative changes in membrane
      spanning sequences, such as the introduction of charged residues. Nevertheless,
      the greatest clustering of substitutions occurred in the two regions of lac
      permease thought to be most important for transport function. The existence of
      this clustering indicates that even highly non-conservative substitutions may
      cause relatively localized structural defects. Conservative inactivating
      substitutions were scattered throughout lac permease and may affect residues that
      make contacts required for normal folding. Two unexpected phenotypes were
      observed in the collection of mutants: about 20% of the substitutions led to cold
      sensitive lactose utilization, and one substitution made the mutant lac permease
      toxic to cells. This relatively unbiased collection of mutants should provide a
      resource for further studies of how missense mutations inactivate membrane
      proteins in vivo.

PMID- 9514764
TI  - Smaller, faster ribozymes reveal the catalytic core of Neurospora VS RNA.
AB  - We have investigated the structural requirements for cis-cleavage of the VS
      ribozyme by designing deletions, substitutions, and circular permutations based
      on the secondary structure model. Four of the six helices predicted in the model
      have been shortened, resulting in self-cleaving RNAs of only 121 to 126
      nucleotides. Remarkably, the shorter ribozymes exhibit a 30 to 40-fold faster cis
      cleavage rate. The increase in activity results from disrupting an inhibitory
      helix whose 5' side contains bases upstream of the cleavage site, and from
      constructing a circular permutation that tethers the helix containing the
      cleavage site to a shortened version of the rest of the ribozyme. The non
      essential regions identified by the deletions map to the periphery of a recently
      proposed structure model, revealing a central ribozyme core that contains the
      essential structural elements required for activity of the VS ribozyme.

PMID- 9514766
TI  - Simulations of the structural and dynamical properties of denatured proteins: the
      "molten coil" state of bovine pancreatic trypsin inhibitor.
AB  - The dynamic nature of denatured, unfolded proteins makes it difficult to
      characterize their structures experimentally. To complement experiment and to
      obtain more detailed information about the structure and dynamic behavior of the
      denatured state, we have performed eleven 2.5 ns molecular dynamics simulations
      of reduced bovine pancreatic trypsin inhibitor (BPTI) at high temperature in
      water and a control simulation at 298 K, for a total of 30 ns of simulation time.
      In a neutral pH environment (acidic residues ionized), the unfolded protein
      structures were compact with an average radius of gyration 9% greater than the
      native state. The compact conformations resulted from the transient formation of
      non-native hydrophobic clusters, turns and salt bridges. However, when the acidic
      residues were protonated, the protein periodically expanded to a radius of
      gyration of 18 to 20 A. The early steps in unfolding were similar in the
      different simulations until passing through the major transition state of
      unfolding. Afterwards, unfolding proceeded through one of two general pathways
      with respect to secondary structure: loss of the C-terminal helix followed by
      loss of beta-structure or the opposite. To determine whether the protein
      preferentially sampled particular conformational substates in the denatured
      state, pairwise Calpha root-mean-square deviations were measured between all
      structures, but similar structures were found between only two trajectories. Yet,
      similar composite properties (secondary structure content, side-chain and water
      contacts, solvent accessible surface area, etc.) were observed for the structures
      that unfolded through different pathways. Somewhat surprisingly, the unfolded
      structures are in agreement with both past experiments suggesting that reduced
      BPTI is a random coil and more recent experiments providing evidence for non
      random structure, demonstrating how ensembles of fluctuating structures can give
      rise to experimental observables that are seemingly at odds.

PMID- 9514768
TI  - A competition model of exogenous orienting in 3.5-month-old infants.
AB  - Four experiments are reported on exogenous (stimulus-driven) orienting in 3.5
      month-old infants. A small moving bar embedded in a field of static bars was used
      to draw the infant's attention to one side of the display or the other. The bars
      could be either red or green. In all four of these experiments sensitivity to
      this small moving bar was affected significantly by how unevenly the red and
      green bars were distributed across the visual field. Sensitivity to the moving
      bar was lower when most of the red bars were in the field contralateral to this
      probe suggesting competition between the motion stimulus and contralaterally
      placed red but not green bars on a small, but significant proportion of trials.
      This basic effect replicated in four separate experiments and depended coarsely
      on how unevenly the red and the green bars were distributed across the field. A
      competition model of exogenous orienting with a winner-take-all rule captured the
      most important features of the data. The distribution of color within the visual
      field can bias attention significantly at 3.5 months making it either more or
      less likely that an infant will detect a moving stimulus.

PMID- 9514770
TI  - Call for papers 
AB  - Copyright

PMID- 9514769
TI  - Contribution of central and peripheral vision to the regulation of stance:
      developmental aspects.
AB  - Postural oscillations in 6-, 8-, and 10-year-old children were analyzed in four
      conditions of vision of the environment (complete vision, peripheral vision,
      central vision and no-vision) and two conditions of ankle somatosensory
      information (normal and altered support surfaces with a 5-cm-thick foam).
      Children were more stable with than without vision. This was observed whether
      children had complete or partial vision (central or peripheral). They were also
      more stable with the normal than with the altered support surface. Overall, there
      was no effect of age. Beyond these well-established results, the present
      experiment showed the complementary role of peripheral and central vision in the
      regulation of children's posture. For the 6- and 10-year-olds, central and
      peripheral vision yielded similar postural stability, whereas for the 8-year
      olds, central vision yielded greater postural stability than peripheral vision.
      The analysis of postural oscillations in the medio-lateral and antero-posterior
      planes showed that, for the three age groups, central vision was as efficient
      whatever the plane. On the other hand, after age 6, peripheral vision was more
      efficient for regulating antero-posterior than medio-lateral oscillations. The
      contribution of the different sensory systems and their interaction for
      stabilizing posture in children should be specifically interpreted with regard to
      the operating characteristics of each sensory system at each age.

PMID- 9514771
TI  - Childhood anxiety and memory functioning: a comparison of systemic and processing
      accounts.
AB  - Information-processing models of childhood anxiety highlight the centrality of
      memory processes in the maintenance and intensification of anxiety. Recent
      advances in memory research allow for an increasingly fine-grained analysis of
      the relation between anxiety and memory. The relation between childhood anxiety
      and memory was examined in a sample of 160 high- and low-trait-anxious sixth
      through eighth grade children. Results indicated that anxiety predicted a memory
      bias toward negative relative to neutral information during conceptual but not
      perceptual tasks. Further, anxiety predicted a memory bias toward positive
      relative to neutral information on procedural tasks and a memory bias away from
      positive relative to neutral information on declarative tasks. These findings
      accent the complexity and multidimensionality of relations among childhood
      anxiety, the emotional valence of stimuli, types of cognitive processing, and
      memory systems in contributing to biases in children's memory functioning.

PMID- 9514772
TI  - Time estimation in young children: an initial force rule governing time
      production.
AB  - Children aged 3 and 5 1/2 years were asked to carry out a response duration task
      in two sessions under "minimal", "temporal" and "force" instructions. In session
      1, they were told to press "long enough" for the temporal instructions and "hard
      enough" for the force instructions. In session 2, they were asked to press
      "longer" or "harder" than in the previous session. Results showed that the force
      instructions, but not the temporal instructions, improved the 3-year-olds' timing
      accuracy. Furthermore, when instructed to press harder, 3-year-olds pressed
      longer. In contrast, 5 1/2-year-olds were more accurate with the temporal than
      with the force instructions; and when asked to press harder, they did not press
      longer. These findings suggest that 3-year-olds rely on a certain amount of force
      to produce correct response durations. The marked dissociation between force and
      duration only emerges between the ages of 3 and 5 1/2.

PMID- 9514774
TI  - Fast passive elution of DNA from zinc-imidazole negatively stained polyacrylamide
      gels.

PMID- 9514773
TI  - Development of an assay for bioactive insulin.
AB  - A method to detect the biological activity of serum insulin has been developed.
      This method, called a bioactive insulin assay, determines the ability of serum
      insulin to stimulate the autophosphorylation of insulin receptors in an intact
      cell system. For this, intact Chinese hamster ovary cells which overexpress the
      human insulin receptor are treated with serum and then lysed. Autophosphorylation
      of the insulin receptors is then measured by a two-site immunofluorometric assay
      using monoclonal anti-insulin receptor antibodies and europium-labeled anti
      phosphotyrosine antibodies. The detection limit of this assay is 1 microU/ml of
      insulin. Dilution and recovery test inter- and intraassay coefficient variations
      are permissible. The amount of insulin determined by this assay correlated well
      with the amount of insulin detected by a traditional immunological assay for
      insulin (r = 0.94, P < 0.001). In the case of a mutant insulin, the insulin from
      a Wakayama subject, the biologically active insulin was found to constitute 9% of
      the immunologically reactive insulin. Since this assay specifically measures the
      amount of biologically active insulin present in serum, it should be particularly
      useful in monitoring active insulin in patients with various mutant insulins.

PMID- 9514775
TI  - Artifactual hybridization bands associated with the pulsed field gel
      electrophoresis of partially digested yeast chromosomes.

PMID- 9514776
TI  - Integrated cell isolation and polymerase chain reaction analysis using silicon
      microfilter chambers.
AB  - White blood cells are isolated from whole blood in silicon-glass 4.5-microliter
      microchips containing a series of 3.5-micron feature-sized 'weir-type' filters,
      formed by an etched silicon dam spanning the flow chamber. Genomic DNA targets,
      e.g., dystrophin gene, can be directly amplified using the polymerase chain
      reaction (PCR) from the white cells isolated on the filters. This dual function
      microchip provides a means to simplify nucleic acid analyses by integrating in a
      single device two key steps in the analytical procedure, namely, cell isolation
      and PCR.

PMID- 9514777
TI  - Degenerate oligonucleotide primed-polymerase chain reaction and capillary
      electrophoretic analysis of human DNA on microchip-based devices.
AB  - Random amplification of the human genome using the degenerate oligonucleotide
      primed-polymerase chain reaction (DOP-PCR) was performed in a silicon-glass chip.
      An aliquot of the DOP-PCR amplified genomic DNA was then introduced into another
      silicon-glass chip for a locus-specific, multiplex PCR of the dystrophin gene
      exons in order to detect deletions causing Duchenne/Becker muscular dystrophy.
      Amplicons were analyzed by both conventional capillary electrophoresis and
      microchip electrophoresis and results were compared to those obtained using
      standard non-chip-based PCR assays. Results from microchip electrophoresis were
      consistent with those from conventional capillary electrophoresis. Whole genome
      amplification products obtained by DOP-PCR proved to be a suitable template for
      multiplex PCR as long as amplicon size was < 250 bp. Successful detection and
      resolution of all PCR products from the multiplex PCR clearly shows the
      feasibility of performing complex PCR assays using microfabricated devices.

PMID- 9514778
TI  - A microplate fluorimetric assay for transfection of the beta-galactosidase
      reporter gene.

PMID- 9514780
TI  - Determining the number of essential ligand binding sites in enzymes using the
      slopes of the Wang-Srivastava plots.

PMID- 9514779
TI  - A microtiter plate assay for the determination of uronic acids.
AB  - The amount of uronic acid residues in samples containing glycosaminoglycans or
      pectin is an important parameter in the quantitative and structural analysis of
      these complex carbohydrates. This paper describes a method to determine the
      content of uronic acids in biological samples, using conventional polystyrene
      microtiter plates and microtiter plate-reading equipment with standard
      interference filters (i.e., 540 or 492 nm). This assay is a modification of a
      commonly used procedure, viz. hydrolysis of uronic acid containing carbohydrate
      polymers in 80% sulfuric acid containing tetraborate ions at 80 degrees C
      followed by a coloring step with an m-hydroxydiphenyl reagent at room
      temperature. The use of microtiter plates has several practical advantages: (i)
      less risk of handling hot, concentrated sulfuric acid is present; (ii) an
      accurate estimate of background absorbance by multiple reading of the plates is
      possible; and (iii) many samples can be assayed in one series without errors due
      to fading of the final color. The validity of the assay was checked for the
      quantification of hyaluronic acid in equine synovial fluid samples. We consider
      this the method of choice when a large number of samples must be analyzed for
      their content of uronic acid residues.

PMID- 9514781
TI  - Quantitative measurement of superoxide generation and oxygen consumption from
      leukocytes using electron paramagnetic resonance spectroscopy.
AB  - In view of the important role of superoxide in cellular injury, there has been a
      great need for methods suitable for quantitation of superoxide production from
      cells. Previous methods have had limited sensitivity or specificity as well as
      problems with side reactions in cellular systems. Recently, we have shown that
      the new spin trap 5-(diethoxyphosphoryl)-5-methyl-1-pyrroline-N-oxide has ideal
      properties for quantitative superoxide measurement in chemical/biochemical
      systems; however, its suitability and potential for measurements in cellular
      systems has not been determined. Therefore, we evaluated the use of DEPMPO for
      quantitative measurement of superoxide formed by polymorphonuclear leukocytes.
      After activation of these cells with the phorbol ester (PMA, 200 ng/ml) or
      opsonized zymosan (1 mg/ml) at 24 degrees C a strong signal of the superoxide
      adduct, DEPMPO-OOH, was observed. This technique was highly sensitive and enabled
      measurement of superoxide generation from as few as 2 x 10(3) cells. The kinetics
      of adduct formation and decay were measured which enabled quantitation of
      superoxide formation. Spin label electron paramagnetic resonance (EPR) oximetry
      was used to measure the oxygen consumption from these cells. With PMA activation
      rapid onset of superoxide generation occurred with a rate of 0.78 nmol/min/10(6)
      cells while with zymosan a slower gradual onset of activation was seen to a peak
      rate of 0.061 nmol/min/10(6) cells. With both stimulators the ratios of
      superoxide production to oxygen consumption were similar with values of
      approximately 50% obtained. Thus, EPR spin trapping with DEPMPO together with EPR
      oximetry methods can be used to provide sensitive and specific quantitation of
      cellular superoxide generation and oxygen consumption. These methods provide a
      promising new approach for the measurement of oxygen reduction and superoxide
      generation in cellular systems.

PMID- 9514782
TI  - Enzymatic synthesis of a neoglycoconjugate by transglycosylation with
      Arthrobacter endo-beta-N-acetylglucosaminidase: a substrate for colorimetric
      detection of endo-beta-N-acetylglucosaminidase activity.
AB  - The transglycosylation activity of endo-beta-N-acetylglucosaminidase from
      Arthrobacter protophormiae was used for the enzymatic synthesis of a novel
      oligosaccharide, Man6GlcNAc-p-nitrophenyl-alpha-D-glucose (Man6GlcNAc-Glc-pNP).
      The reaction was efficiently induced in aqueous solution containing dimethyl
      sulfoxide. In the medium containing 20% (v/v) dimethyl sulfoxide with 0.1 M Glc
      pNP as an acceptor, the transglycosylation attained yields of 75% by high
      performance anion-exchange chromatography. The structure of Man6GlcNAc-Glc-pNP
      was confirmed by ion mass spectrometry and 400 MHz 1H NMR spectrometry. Various
      endo-beta-N-acetylglucosaminidases hydrolyzed this oligosaccharide and Man6GlcNAc
      and Glc-pNP were released from the oligosaccharide by endo-beta-N
      acetylglucosaminidase digestion. We have established a new procedure for the
      colorimetric detection of endo-beta-N-acetylglucosaminidase activity using
      Man6Glc-NAc-Glc-pNP, which is simple as that for other exoglycosidase assays with
      pNP-glycosides as substrates.

PMID- 9514783
TI  - Determination of transport parameters of permeant substrates of the vesicular
      amine transporter.
AB  - Biological transport of moderately permeant compounds is obscured by diffusion of
      the compounds back across the membrane, so characterization of the transport of
      such compounds requires correction for permeability. A relatively simple method
      for determining kinetic parameters for moderately permeant compounds is presented
      here. After evaluating a compound's apparent permeability coefficient, its steady
      state uptake is measured as a function of concentration. By comparing the
      concentration dependence of uptake measured both in the presence and in the
      absence of a complete inhibitor of the transporter, K(m) and Vmax for transport
      of that substrate may be calculated. When used to analyze transport of tyramine
      and hydroxyephedrine by the vesicular amine transporter, this method yields
      results consistent with other methods and with values for analogous impermeant
      substrates. In bovine adrenal chromaffin vesicles, tyramine and (-)erythro
      hydroxyephedrine have apparent permeability coefficients of 4.7 +/- 1.0 x 10(-9)
      and 1.1 +/- 0.4 x 10(-8) cm/s, respectively. Values for K(m) are 15 +/- 9 and 34
      +/- 14 microM and for Vmax are 1.3 +/- 0.2 and 1.4 +/- 0.9 nmol/min.mg of
      membrane protein, respectively.

PMID- 9514784
TI  - Mass spectrometric determination of the sites of O-glycan attachment with low
      picomolar sensitivity.
AB  - A sensitive protocol for unambiguously and positively identifying O-glycosylation
      sites in glycopeptides is described, based on beta-elimination of the glycan
      chain(s) using NH4OH. On glycan elimination, NH3 is incorporated into the amino
      acid residue(s) to which the glycan(s) had been attached, to yield a modified
      amino acid residue having a distinct mass. Electrospray ionization collision
      induced dissociation tandem mass spectrometry allows the released, modified
      peptide to be sequenced and the site(s) of the modified amino acid residue(s) to
      be identified. The protocol has been optimized using a series of structurally
      related O-glycopeptides, and standard conditions are recommended for handling
      unknowns. We demonstrate that site determination can be achieved using as little
      as 1 pmol of starting material.

PMID- 9514785
TI  - Differential subtraction display: a unified approach for isolation of cDNAs from
      differentially expressed genes.
AB  - We have developed a novel efficient approach, termed differential subtraction
      display, for the identification of differentially expressed genes. Several
      critical parameters for the reproducibility and enhanced sensitivity of display,
      as well as steps to reduce the number of false positive cDNA species, have been
      defined. These include- (a) use of standardized oligo(dT)-primed cDNA pools
      rather than total RNA as the starting material for differential display, (b)
      critical role of optimal cDNA input for each distinct class of primers, (c)
      phenomena of primer dominance and interference, and (d) design of a novel set of
      enhanced specificity anchor primers. Introduction of an efficient subtractive
      hybridization step prior to cloning of cDNA species enriches the bona fide cDNA
      species that are either exclusively present in one sample (+/-) or show altered
      expression (up-/down-regulation) in RNA samples from two different tissues or
      cell types. This approach, in comparison to differential display, has several
      advantages in terms of reproducibility and enhanced sensitivity of display
      coupled to the cloning of enriched bona fide cDNA species corresponding to
      differentially expressed RNAs.

PMID- 9514786
TI  - Development of an enzyme-linked immunosorbent assay-based method for measuring
      galactosyltransferase activity using a synthetic glycopolymer acceptor substrate.
AB  - A lectin-assisted enzyme-linked immunosorbent assay (ELISA)-based method using a
      synthetic glycopolymer as an acceptor substrate was developed for measuring beta
      1,4-galactosyltransferase (GalT) activity. A polyacrylamide derivative having a
      beta-linked N-acetylglucosamine (GlcNAc beta) moiety on each monomeric unit was
      synthesized chemically and immobilized on a polystyrene microtiter plate as an
      acceptor substrate for GalT. After the plate was incubated with bovine GalT, the
      enzyme reaction product, beta-linked Gal residue on the polyacrylamide-bound
      GlcNAc residue, was detected by using Ricinus communis agglutinin 1 (RCA1),
      rabbit anti-RCA1 antibody, and a peroxidase-labeled anti-rabbit IgG. The lowest
      GalT concentration detectable by this method was about 0.5 mU/ml, which is
      comparable to those by the previously reported ELISA-based assays. The unique
      property of the glycopolymer, PAP(GlcNAc beta), of binding noncovalently but
      tightly to the polystyrene microtiter plate allowed the use of this acceptor
      substrate for the GalT activity measurement even in the presence of 1% Triton CF
      54 and X-100. Our system was successfully applied to assess GalT activity in milk
      of various mammals.

PMID- 9514787
TI  - Determination of diethylpyrocarbonate-modified amino acid residues in alpha 1
      acid glycoprotein by high-performance liquid chromatography electrospray
      ionization-mass spectrometry and matrix-assisted laser desorption/ionization time
      of-flight-mass spectrometry.
AB  - The chemical modification reagent diethylpyrocarbonate (DEPC) was used to modify
      alpha 1-acid glycoprotein (orosomucoid, OMD) under various conditions. The
      extents of DEPC modification of the histidine and tyrosine residues were followed
      by UV spectrophotometry. The resulting modified OMD was analyzed using enzyme
      digestion, reverse-phase HPLC, electrospray ionization-mass spectrometry
      (ESI/MS), and matrix-assisted laser desorption ionization time-of-flight-mass
      spectrometry (MALDI-TOF/MS). The inherent problem of instability of DEPC-modified
      histidine residues was overcome by adjusting the time scale of the postreaction
      processing of modified OMD. There were observed differences in reactivity of
      histidine 97 and histidine 100 that were consistent throughout the pH range 6-8.
      Furthermore, several lysine residues were modified and the amount of modification
      increased over the pH range 6-8. These experiments show that HPLC-ESI/MS and
      MALDI-TOF/MS analysis coupled with enzyme digestion provide the necessary
      information to describe the reaction of DEPC with OMD. In addition, the results
      provide the carbethoxy-histidine stability and histidine reactivity information
      of DEPC-modified OMD necessary for the design of experiments to characterize the
      drug binding properties of OMD.

PMID- 9514788
TI  - Analysis of partially methyl-esterified galacturonic acid oligomers by high
      performance anion-exchange chromatography and matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry.
AB  - Two methods were developed to detect partially methyl-esterified galacturonic
      acid oligomers, generated by endopolygalacturonase treatment of a 30% methyl
      esterified pectin. The enzyme digest was shown, by matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry, to contain sodiated
      galacturonic acid oligomers with a degree of polymerization of 2-12, containing 0
      6 methyl esters. Galacturonic acid (monomer) could not be detected because of
      matrix ions interference in the low mass region. Using high-performance anion
      exchange chromatography, with a sodium acetate gradient at pH 5.0 and postcolumn
      sodium hydroxide addition to allow pulsed amplified detection, a complex elution
      profile was obtained with the endopolygalacturonase-treated 30% methyl-esterified
      pectin. All the components eluted before nonesterified tetragalacturonic acid.
      The partially methyl-esterified oligogalacturonic acids eluted in a discernible
      series of oligomers with an identical number of nonesterified carboxylic acid
      groups; the large, more esterified oligomers eluted before small, less esterified
      oligomers. The methyl esters may hinder the interaction of the neighboring
      carboxylic acid groups with the anion-exchange resin, thereby giving the
      components an apparent lower overall negative charge.

PMID- 9514789
TI  - Quantification of jasmonic acid, methyl jasmonate, and salicylic acid in plants
      by capillary liquid chromatography electrospray tandem mass spectrometry.
AB  - Jasmonic acid, methyl jasmonate, and salicylic acid have been reported to occur
      in plants and are thought to be essential for the regulation of systemic defense
      responses. This work describes a method for the quantitation in plant tissue of
      these regulators by reverse-phase capillary liquid chromatography interfaced to
      an electrospray tandem mass spectrometer. Inclusion during sample preparation of
      hydrogenated and/or deuterated internal standards corresponding to analogs of the
      regulators compensated for sample loss and permitted quantitation using the
      multiple reaction monitoring mode of the mass spectrometer. The free acids were
      analyzed in a negative-ion mode, whereas methyl jasmonate was analyzed in a
      positive-ion mode. Using these procedures an extract of fresh hybrid poplar
      leaves was found to contain per gram of leaf tissue 2.6 micrograms of jasmonic
      acid, 1.3 micrograms of methyl jasmonate, and 31.0 micrograms of salicylic acid.
      The techniques used should be applicable to other plant materials.

PMID- 9514790
TI  - Biotinylated proteins of Pasteurella multocida and Pasteurella haemolytica cause
      false-positive reactions with biotinylated probes in colony lift-hybridization
      assays.

PMID- 9514791
TI  - Development of a scintillation proximity assay for peroxisome proliferator
      activated receptor gamma ligand binding domain.
AB  - A scintillation proximity assay for peroxisome proliferator-activated receptor
      gamma ligand binding domain is described. Scintillation proximity offers an
      equilibrium method for detecting ligands that is both cost effective and fully
      automatable. The method described here is the first reported scintillation
      proximity assay for a peroxisome proliferator-activated receptor. The design of
      this system is generic in nature, allowing it to be adapted for other ligand
      binding proteins.

PMID- 9514792
TI  - A positive selection vector for cloning of long polymerase chain reaction
      fragments based on a lethal mutant of the crp gene of Escherichia coli.
AB  - We have constructed a cloning vector with a tight positive selection for
      recombinant clones in Escherichia coli. The positive selection pressure results
      from a lethal mutation within the E. coli gene coding for the catabolite gene
      activator protein CAP, which is disrupted whenever a fragment is successfully
      inserted. Here, we show that this "suicide" vector, pCAPs, is suitable for
      cloning of PCR products as long as 9.3 kb into several unique restriction sites
      which are scattered throughout the lethal gene.

PMID- 9514793
TI  - Detection of hepatitis C virus helicase activity using the scintillation
      proximity assay system.
AB  - The C-terminal two-thirds of the nonstructural protein 3 (NS3) of hepatitis C
      virus (HCV) possesses RNA helicase activity. This enzyme is considered to be
      involved in the viral replication and is expected to be one of the target
      molecules of anti-HCV drugs. The conventional method for the measurement of RNA
      helicase activity includes the step of gel electrophoresis which makes the
      screening of multiple samples inconvenient. In this study, to establish a high
      throughput screening system for HCV helicase inhibitors, we applied the
      scintillation proximity assay (SPA) system to the detection of this enzymatic
      activity. We could detect the helicase activity using the NS3 protein purified by
      an immunoaffinity column. The activity was dependent on the concentration of the
      enzyme and the reaction time. The RNA helicase activity measured by the SPA
      system was in a good correlation with that obtained by the conventional method.
      Furthermore, the SPA system showed better reproducibility and less deviation of
      the data than the conventional method, which makes the former suitable for
      quantitative analysis. Since any separation step is not required and microtiter
      plates can be used in this method, it has the advantage of dealing with multiple
      samples.

PMID- 9514794
TI  - A more sensitive Hummel assay for chymotrypsin.

PMID- 9514795
TI  - Spectroscopic and kinetic characterization of eosin-5-maleimide.
AB  - Eosin-5-maleimide (EM) is an increasingly important and widely used probe in the
      study of membrane protein structure and function. Yet little is known about its
      spectral properties in hydrophobic and hydrophilic environments. Furthermore, EM
      is hydrolyzed faster than the traditional N-ethylmaleimide. To offer a more solid
      foundation for the use of EM in studies of membrane protein structure and
      function, we have undertaken a detailed study of the absorbance and fluorescence
      spectra of EM, eosin-5-maleic acid, and the L-cysteine and beta-mercaptoethanol
      adducts of EM in aqueous and hydrophobic environments; we have studied the
      kinetics of hydrolysis of EM in various environments, and we have investigated
      the reaction kinetics of EM with L-cysteine.

PMID- 9514796
TI  - A method for fluorescence in situ hybridization against synaptonemal complex
      associated chromatin of plant meiocytes.
AB  - An improved method of preparing two-dimensional surface spreads of plant
      synaptonemal complexes (SCs) associated with fluorescent in situ hybridization is
      described. This technique produces clear preparations of SCs and, in addition,
      consistently reveals the organization and location of different repetitive DNA
      sequences in plant meiotic prophase chromosomes.

PMID- 9514797
TI  - Analysis of failures after negative second-look in patients with advanced ovarian
      cancer: an Italian multicenter study.
AB  - This multicenter retrospective study is based on 192 patients with advanced
      ovarian cancer in pathological complete response at second-look surgery. Ninety
      four (48.9%) patients developed recurrent disease after a median time of 18
      months (range, 4-89 months) from surgical reassessment. The recurrence involved
      the pelvis in 45 (47.9%) cases, the abdomen in 42 (44.7%), the retroperitoneal
      lymph nodes in 13 (13.8%), and distant sites in 20 (21.2%). On the whole series,
      5- and 7-year disease-free survival rates after negative second-look were 47.4
      and 44.5%, respectively. By log-rank test the disease-free survival rate was
      related to FIGO stage (P = 0.008), tumor grade (P = 0.0021), size of residual
      disease after initial surgery (P = 0.0038), and type of second-look (laparoscopy
      vs laparotomy, P = 0.0061), but not to histological type and first-line
      chemotherapy. Cox proportional hazard model showed that tumor grade, size of
      residual disease, and type of second-look were independent prognostic variables
      for disease-free survival. The risk ratio of relapse was 2.386 (95% CI, 1.140
      4.990) for grade 2 and 3.118 (95% CI, 1.515-6.416) for grade 3 compared to grade
      1 disease. For patients with residual disease 1-2 cm and > 2 cm the risk ratio
      was, respectively, 1.877 (95% CI, 1.117-3.156) and 2.156 (95% CI, 1.324-3.511)
      compared to patients with residual disease < 1 cm. The risk ratio was 1.826 (95%
      CI, 1.121-2.973) for patients who were submitted to a laparoscopic second-look
      compared to those who underwent a laparotomic reassessment. Poorly differentiated
      grade and large residual disease after initial surgery are the strongest
      prognostic variables for recurrence after a negative second-look.

PMID- 9514798
TI  - Recurrent psammocarcinoma of the peritoneum with complete response to tamoxifen
      therapy.
AB  - Psammocarcinoma is a rare type of serous carcinoma arising from the ovary or
      peritoneum, characterized by massive psammoma body formation, invasiveness, and
      low-grade cytological features. A case of primary peritoneal psammocarcinoma is
      presented. Aspects of clinical presentation, diagnosis, and management are
      described. Emphasis is placed on successful management of recurrent disease using
      tamoxifen therapy.

PMID- 9514799
TI  - Response to salvage treatment in recurrent ovarian cancer treated initially with
      paclitaxel and platinum-based combination regimens.
AB  - OBJECTIVE: The aim of this study was to evaluate the response to salvage
      treatment in recurrent ovarian cancer treated initially with paclitaxel-based
      chemotherapy. METHODS: A retrospective review of patients with recurrent ovarian
      cancer treated with surgical debulking and paclitaxel-based chemotherapy was
      performed. All cases received second-line treatment with a response evaluated by
      clinical or surgical means. Data analysis was conducted using the SAS statistical
      package. RESULTS: Fifty cases of advanced stage disease were available for
      review. Patients received paclitaxel and cisplatin or carboplatin with a 72.0%
      response rate. The median time to recurrence after primary treatment was 6
      months. Second-line treatment included cisplatin or carboplatin (50%), Taxol
      (10%), or lutetium (22%), an intraperitoneal radiolabeled monoclonal antibody
      targeted to TAG-72. A 52.0% clinical response to salvage treatment was detected.
      With a median follow-up of 7 months, 68.0% of patients had experienced recurrence
      or progression of their disease. The median time to second recurrence was 5
      months. Cases sensitive to initial paclitaxel-containing chemotherapy responded
      to any of the salvage treatments more frequently than chemotherapy-resistant
      tumors (88.5% versus 11.5%, P < 0.05). CONCLUSIONS: Recurrent ovarian cancer
      patients initially treated with paclitaxel-based chemotherapy frequently
      responded to salvage treatment. However, the duration of response was brief, and
      hospitalization for treatment-related side-effects was common. Tumor response to
      initial paclitaxel/platinum treatment was predictive of future response to second
      line agents. Current salvage therapies appear to provide little benefit in cases
      of tumors resistant to primary chemotherapy.

PMID- 9514800
TI  - Histology corresponding to mildly dyskaryotic smears--a study of 190 laser cone
      biopsied patients.
AB  - OBJECTIVES: The aim of the study was to evaluate the histological outcome of
      laser ring biopsies in patients with one or more smears showing cytological mild
      dyskaryosis where punch biopsies were not performed. The possibilities of
      predicting histological findings of CIN 2 and CIN 3 were analyzed. METHODS: The
      study comprised 190 laser ring biopsied patients with mildly dyskaryotic smears.
      Eighty-five patients were excluded from the initial 275 because of up- and
      downgrading of smears. Conization specimens and smears were reviewed by an
      experienced histopathologist and two experienced cytotechnicians. The
      histological findings were correlated to smear findings. RESULTS: Histologically,
      CIN 2 was found in 60 and CIN 3 in 45 patients (31 and 24%, respectively). The
      incidence of histological CIN 3 was higher in those with two or more mildly
      dyskaryotic smears and in those dyskaryotic smears lacking koilocytic change.
      Mildly dyskaryotic smears without endocervical cells indicated higher incidence
      of histological CIN 3. The fact that 36 of 96 CIN 2 and 3 lesions (38%) involved
      only 3 mm or less of the mucosa might be one important explanation for the
      absence of representative cells in the corresponding smears. CONCLUSIONS: Our
      study has shown that a mildly dyskaryotic smear is a strong indicator of CIN 2-3
      histologically, especially in those cases without koilocytic cells and in those
      with repeatedly abnormal smears. The importance of inadequate sampling is
      indicated by higher incidence of histological CIN 3 in those with less than
      optimal smears. These findings are some of the factors to be taken into account
      when planning treatment strategies for this group of patients.

PMID- 9514801
TI  - Differential expression of trypsin in human ovarian carcinomas and low-malignant
      potential tumors.
AB  - It is widely recognized that matrix metalloproteinases and serine proteinases
      play an important role in cancer invasion and metastasis. We have reported that
      trypsin is synthesized in ovarian carcinomas as well as in some other types of
      cancers. In general, ovarian cancers easily tend to invade, metastasize, and
      spread widely into the peritoneal cavity. However, low-malignant-potential (LMP,
      borderline tumor) ovarian tumors are known to have limited malignant potential
      for progression, although microinvasion and distant metastasis have been reported
      among them. To analyze the relationship between varied degrees of trypsin
      expression and malignant behavior of ovarian tumors, immunohistochemical studies
      with monoclonal antibodies to human trypsin and clinicopathologic analysis were
      performed in human ovarian carcinomas, low-malignant-potential tumors, and benign
      cystadenomas. Thirteen (44.8%) cases of 29 ovarian carcinomas showed prominent
      trypsin expression, while only 2 (18.2%) cases of 11 LMP ovarian tumors
      demonstrated low levels of expression. Benign tumors and normal ovaries did not
      show any positivity for trypsin. These data suggest that tumor-derived
      heterotropic trypsin may be associated with ovarian tumors in parallel with
      malignant potential or behavior such as invasiveness or metastasis. At least in
      some ovarian carcinomas, prominent stromal invasion or metastasis might require
      the acquisition of or association with tumor-derived trypsin production.

PMID- 9514803
TI  - Expression of p16INK4 and retinoblastoma protein Rb in vulvar lesions of Chinese
      women.
AB  - The protein products of the two tumor suppressor genes located on 9p and 13p,
      p16INK4 and Rb, respectively, play an important role in regulation of the cell
      cycle and are implicated in tumorigenesis. We examined 49 cases of benign vulvar
      lesions, vulvar intraepithelial neoplasia (VIN), and squamous cell carcinoma with
      immunohistochemical staining to determine expression of p16INK4 and Rb. All and
      86% of benign lesions expressed Rb and p16INK4, respectively; 40% each of VIN I
      and VIN III expressed p16INK4 and Rb, respectively; and 37 and 68% of squamous
      cell carcinomas expressed p16INK4 and Rb, respectively. The combination of the
      lack of p16INK4 and/or Rb expression increased from benign lesions (14.3%),
      through VIN I (60%) and VIN III (60%), to invasive squamous cell carcinoma (72%),
      thus supporting the postulation that alterations in p16INK4 or Rb could be
      significant events in progression of disease. The loss of Rb expression also
      increased from stage I carcinoma (16.7%) through stage II (26.7%) and III
      (44.4%), to IV (50%), suggesting that Rb may play an important role in tumor
      progression. A larger study on VIN lesions and genetic coding is suggested to
      further investigate the role of p16INK4, Rb, and other factors in tumorigenesis
      and progression of vulvar cancers.

PMID- 9514802
TI  - Combined carboplatin plus ifosfamide and cisplatin in patients with advanced
      ovarian carcinoma. A phase I-II study. GOCS (Gynecological Oncology Cooperative
      Study).
AB  - Because of the relative lack of overlapping toxicity, carboplatin (PPL) and
      cisplatin (CDDP) can be easily combined for treatment of ovarian cancer to
      increase total platinum dose intensity. Ifosfamide (IFO), one of the most
      effective single agents in ovarian cancer, has a low hematological toxicity when
      administered in continuous infusion. From January 1991 to December 1993, 34
      patients with advanced ovarian cancer, previously untreated with chemo- or
      radiotherapy, were enrolled in a phase I-II study with the aim of determining the
      maximum tolerated dose (MTD) of CDDP (on day 8 of a 28-day cycle) in combination
      with PPL (300 mg/m2 on day 1) and IFO (4,000 mg/m2/24 h by continuous infusion on
      day 1). The initial dose level of CDDP was 40 mg/m2, which was continuously
      increased by 10 mg/m2 up to the MTD defined as one dose level below that inducing
      dose-limiting toxicity (DLT) in at least two-thirds of treated patients; no dose
      escalation was allowed in the same patient. Grade 3-4 leukopenia and
      thrombocytopenia were observed in 54 and 49% of patients, respectively. The DLT
      was reached at 70 mg/m2 and therefore the dose recommended for the phase II study
      was 60 mg/m2. Complete (CR) plus partial response was observed in 88% of patients
      with a 21% pathological CR. With a minimum follow-up of 32 months (median 40
      months), median progression-free survival and overall survival were 21 and 39
      months, respectively. In conclusion, the combination of CDDP, PPL, and IFO
      provides an effective regimen for ovarian cancer with an acceptable toxicity
      profile.

PMID- 9514804
TI  - Ovarian metastasis of stage IB1 squamous cell cancer of the cervix after radical
      parametrectomy and oophoropexy.
AB  - We present a case report of a patient with a IB1 cervical squamous cell cancer
      which recurred in a transposed ovary 8 years following radical parametrectomy.
      The patient was initially treated with a simple vaginal hysterectomy for apparent
      CIS but was found to have an invasive squamous cell cancer to a depth of 7 mm
      into the stroma. She was treated with a radical parametrectomy, pelvic
      lymphadenectomy, and ovarian transposition. There was no evidence of residual
      disease. The patient then had an apparent isolated recurrence in her left ovary 8
      years later. Although there are a few cases of stage IB squamous cell cancer
      metastatic to a transposed ovary, this is the first case with such minimal
      primary disease and delayed isolated recurrence.

PMID- 9514805
TI  - Three-hour paclitaxel infusion and carboplatin is an effective outpatient
      treatment for stage III epithelial ovarian cancer.
AB  - OBJECTIVE: The aim of this study was to determine the response rate and toxicity
      of a 3-h paclitaxel infusion and carboplatin delivered as outpatient therapy for
      the treatment of stage III/IV epithelial ovarian cancer. METHODS: Thirty patients
      with stage III/IV epithelial ovarian cancer underwent cytoreductive surgery. The
      first 10 patients received adjuvant paclitaxel 150 mg/m2 via 3-h infusion on day
      1 and carboplatin 5 times area under the curve on day 2 (group 1) every 28 days.
      The paclitaxel dose was escalated to 175 mg/m2 for the next 20 patients (group
      2). chi 2 and Kaplan-Meier procedures were used for statistical analysis.
      RESULTS: Nine of 51 cycles in group 1 (17.6%) and 19 of 116 cycles (16.4%) in
      group 2 were associated with grade 4 neutropenia (P = 0.96), but only 2 of the
      161 total cycles (0.01%) had fever and neutropenia. One patient in group 1
      experienced grade 3 thrombocytopenia. Two patients in the entire group (7.4%)
      required colony-stimulating factors. One patient in group 2 (3.7%) had grade 3
      neurotoxicity. With a median follow-up of 29 months for the entire group, 5 of 8
      patients (62.5%) in group 1 and 14 of 19 patients (73.7%) in group 2 are alive.
      Median progression-free survival for group 1 and 2 is 13 and 14 months,
      respectively. Median overall survival has not been reached. CONCLUSIONS:
      Paclitaxel via 3-h infusion and carboplatin is an effective outpatient treatment
      for epithelial ovarian cancer that can be safely administered on schedule in the
      majority of patients.

PMID- 9514806
TI  - Mesothelial pelvic lymph node inclusions mimicking metastatic thyroid carcinoma.
AB  - Benign lymph node inclusions are commonly encountered during surgery for
      gynecologic neoplasms and are potential mimics of metastatic disease. A 52-year
      old woman presented with ascites, a complex adnexal mass, and a CA-125 of 1891
      units/mL. A staging laparotomy was performed, diagnosing struma ovarii.
      Pathologic evaluation of pelvic lymph nodes demonstrated mesothelial inclusions
      in nodal sinuses suspicious for metastatic disease. Immunocytochemical evaluation
      revealed benign mesothelial inclusions rather than metastatic thyroid carcinoma.
      Benign mesothelial lymph node inclusions in nodal sinuses are potential mimics of
      metastatic carcinoma. Their presence in pelvic lymph nodes has not previously
      been reported. Given the potential difficulty in determining the origin of these
      inclusions, immunocytochemical evaluation is useful in reaching the correct
      diagnosis.

PMID- 9514807
TI  - Malignant melanoma metastatic to the ovary.
AB  - The diagnosis of malignant melanoma metastatic to the ovary is rarely made in
      living patients. A case of malignant melanoma metastatic to one ovary, skin of
      both axillae, and brain occurring 7 years after wide local excision of the
      primary cutaneous lesion on the patient's back is described. The patient had
      total abdominal hysterectomy, bilateral salpingo-oophorectomy, infracolic
      omentectomy, and selective pelvic retroperitoneal lymphadenectomy, followed by
      whole brain irradiation and chemoimmunotherapy. This case illustrates the
      clinical variability and unpredictable biologic behavior of malignant melanoma
      and it is concluded that malignant melanoma metastatic to the ovary should be
      suspected in any patient who presents with an adnexal mass and has a history of
      malignant melanoma.

PMID- 9514808
TI  - Prognosis of patients treated with whole-brain radiation therapy for metastatic
      gestational trophoblastic disease.
AB  - We evaluated the effect of multiple treatment- and disease-related variables on
      the outcome of patients receiving whole-brain radiation therapy (WBRT) for
      metastatic gestational trophoblastic disease (GTD). Between November 1967 and
      December 1994, 21 patients were treated at our institution for GTD metastatic to
      the brain. All received WBRT, of median 2200 cGy (range 200-3600 cGy). Median
      follow-up, from date of diagnosis of brain metastases, was 77 months (range 11
      170 months). The 5-year actuarial local control of initial brain metastases with
      > or = 2200 cGy was 91%, compared to 24% with < 2200 cGy (P = 0.05). The 2- and 5
      year actuarial survivals of the 9 patients whose disease was controlled at
      extracranial sites were 100 and 83%, respectively, compared to 8 and 0%,
      respectively, for the 12 whose extracranial disease was not controlled (P =
      0.0002). Four (33%) of the patients with persistent or progressive extracranial
      disease later developed new sites of brain metastases, compared to 0% of the
      patients whose extracranial disease was controlled (P = 0.05). Eleven patients
      progressed at their initial site(s) of brain metastasis or developed new
      intracranial lesions; 6 of them died of brain metastases. Survival of patients
      with GTD metastatic to the brain is excellent if extracranial disease can be
      controlled. The total dose of radiation is critical in achieving control of
      initial brain metastases. Patients with uncontrolled extracranial disease are
      more likely to develop new brain metastases. Salvage of intracranial failures
      after WBRT is rare.

PMID- 9514809
TI  - Telomerase activity in the female reproductive tract and neoplasms.
AB  - OBJECTIVE: To study a possible utility of telomerase determination for cancer
      diagnosis. METHODS: In a total of 227 tissue samples comprising 114 normal
      tissues of the reproductive age, 10 fallopian tubes of the postmenopausal age,
      and 103 neoplastic tissues from female reproductive tracts, telomerase activity
      was determined. Using densitometrical analysis, telomerase activity was compared
      between carcinoma tissues and normal counterparts. RESULTS: A total of 97.3%
      (71/73) of cancer samples comprising ovarian carcinoma, endometrial carcinoma,
      and epidermoid carcinoma of the cervix and 89.5% (77/86) of the epithelia of the
      reproductive-aged uterus and fallopian tube showed telomerase activity. The
      epithelia of the fallopian tube of reproductive age showed significantly higher
      frequency of positivity (16/18) than the postmenopausal epithelia of the tube
      (3/10). No difference in telomerase activity was found between endometrial
      carcinomas and normal proliferative endometria. A significantly higher activity
      was found in ovarian epithelial carcinoma and epidermoid carcinoma of the cervix
      than in normal counterparts, although 92% (11/12) of the normal exocervix and 30%
      (3/10) of the normal ovary showed telomerase activity. CONCLUSIONS: Most
      epithelia of the female reproductive tract maintain telomerase activity during
      the reproductive age. Therefore, the detection of malignancies by telomerase
      determination may be feasible in ovarian carcinoma and epidermoid carcinoma of
      the cervix, but requires accurate quantification of telomerase activity.

PMID- 9514811
TI  - Complete hydatidiform mole coexisting with a twin live fetus: clinical course.

PMID- 9514810
TI  - IN MEMORIAM
AB  - Copyright

PMID- 9514812
TI  - Risk of metachronous primary cancers in women with cervical tumor--an Italian
      population-based study.

PMID- 9514813
TI  - Significance of intraperitoneal cytology in patients undergoing radical
      hysterectomy.
AB  - The incidence and prognostic significance of positive intraperitoneal cytology
      taken during a radical hysterectomy was reviewed. A prospective study looking at
      intraperitoneal cytology was conducted by using 400 consecutive radical
      hysterectomies from January 1988 through June 1996. All selected patients had
      peritoneal washings performed prior to a radical hysterectomy with pelvic and
      para-aortic lymphadenectomy. A single pathologist reviewed all cytological and
      histologic specimens. A total of 400 patients were included in the study. Only 7
      of 400 (1.8%) had positive intraperitoneal cytology. Four had squamous cell
      cancer and 3 had adenocarcinoma. Five had stage IB cervical cancer and the
      remainder were stage IIA. Three had positive nodes. Six of 7 had tumor size
      greater than 3 cm. Three of 7 had > 50% invasion and 2 of 7 had lymphovascular
      space invasion. No other risk factors were present in these specimens. Six of 7
      recurred within 18 months of surgery. Recurrences were local or retroperitoneal;
      none were upper abdomen or intraperitoneal. The incidence of positive peritoneal
      cytology during radical hysterectomy is 1.8%. The cost of these cytology
      specimens did not offer an advantage to the current surgical-pathological factors
      used to determine prognosis and adjuvant therapy.

PMID- 9514814
TI  - Telomerase and cancer management: silver bullet or fool's gold?

PMID- 9514815
TI  - The value of repeat cervical cytology at the time of colposcopy.

PMID- 9514816
TI  - Reply
AB  - Copyright

PMID- 9514818
TI  - Zebrafish Genomic Library in Yeast Artificial Chromosomes
AB  - We have constructed a zebrafish yeast artificial chromosome (YAC) library using
      genomic DNA isolated from the inbred AB zebrafish strain. The average insert size
      is 470 kb, estimated from analysis of 155 random selected YACs. The library
      consists of 17,000 clones, providing about a 4.7-fold coverage of zebrafish
      genome. The YAC clones have been arrayed in individual wells of 96-well
      microplates and also pooled to permit rapid polymerase chain reaction screening
      of the entire library. We have also found that the YAC ends can be easily rescued
      and sequenced from pRML1/pRML2-based mini-YAC clones. Copyright 1998 Academic
      Press.

PMID- 9514819
TI  - Synaptic distribution of GluR2 in hippocampal GABAergic interneurons and
      pyramidal cells: a double-label immunogold analysis.
AB  - GluR2 is the regulatory subunit in the AMPA family of glutamate receptors (GluRs)
      in that its presence inhibits calcium flux and dominates the current/ voltage
      characteristics of AMPA receptors. Studies from other laboratories have shown
      that GABAergic interneurons have a lower ratio of GluR2/GluR1 mRNA than pyramidal
      cells as well as possessing AMPA receptors that have a higher relative
      permeability to calcium. We hypothesized that such differences might be related
      to differences in the subunit stoichiometry at the AMPA synapses in each cell
      class, and used a GluR2-specific monoclonal antibody in a double-label immunogold
      protocol with anti-GABA and anti-CaM kinase II to compare the GluR2
      representation at asymmetric synapses in GABA neurons to that of pyramidal cells
      in rat CA1. Virtually all CA1 pyramidal cells as well as the majority of
      GABAergic interneurons were GluR2 positive. EM immunogold labeling also showed
      that GABAergic interneurons had distinctive ultrastructural features and
      contained GluR2 in both their soma and their dendrites, as did the spines and
      shafts of pyramidal cells. GluR2 immunoreactivity was frequently preferentially
      located at asymmetric synapses on both pyramidal cell spines and shafts as well
      as the dendritic processes and soma of GABAergic interneurons. However, the
      labeled synapses on GABAergic neurons had a significantly lower number of
      immunogold particles than those on pyramidal cells. In fact, 90% of the labeled
      asymmetric synapses on GABAergic cells had one to three gold particles, whereas
      greater than 70% of the labeled asymmetric synapses on pyramidal cells had four
      or more gold particles associated with the synapse. These data suggest that while
      both cell classes contain GluR2, they differ in the relative representation of
      GluR2 at their AMPA synapses, such that GABAergic neurons might possess AMPA
      receptors with higher calcium permeability on average than pyramidal cells. Such
      differences in subunit representation at AMPA-receptor-mediated synapses would
      not only lead to differences in calcium permeability and functional
      characteristics across these two cell classes, but might also be relevant to the
      hippocampal patterns of selective vulnerability with respect to excitotoxicity
      and neurodegeneration.

PMID- 9514820
TI  - Selective neuronal vulnerability and specific glial reactions in hippocampal and
      neocortical organotypic cultures submitted to ischemia.
AB  - Neurons from cerebral neocortex and hippocampus exhibit a striking difference in
      vulnerability to transient global ischemia. In order to study the contribution of
      neuronal connections and neuron-glia interactions to this variation in neuronal
      vulnerability, we used hippocampal and neocortical cultures submitted to various
      periods of histotoxic ischemia. Organotypic cultures were exposed at 37 degrees C
      for 0, 7, 30 and 60 min to a glucose-free NaCN-containing medium. Histological
      analysis using thionin staining and MAP2 immunostaining showed differences in the
      temporal profile of neuronal damage in hippocampal and neocortical structures,
      i.e., in decreasing order, CA1 (7 min) > CA3 and neocortical layers II, III, V,
      VI (30 min) > DG and neocortical layer IV (60 min). In parallel to the
      neurodegeneration study, the time course and the regional pattern of microglial
      and astroglial changes were also examined using GS-B4 isolectin and GFAP as
      immunohistochemical markers, respectively. The GS-B4 isolectin staining revealed
      an early (at 7 min for the hippocampus) and a specific microglial activation
      located in areas undergoing neuronal damage. For both organotypic cultures,
      astrogliosis occurred later (after 30 min of stress) with no specific regional
      distribution. Both hippocampal and neocortical cultures submitted to histotoxic
      ischemia allowed the replication of many of the cellular events observed in
      response to global ischemia in vivo. These findings support the hypothesis that
      neuron-neuron connections as well as interactions between neurons and glial cells
      are essential to reproduce in vitro the selective neuronal vulnerability
      described in vivo.

PMID- 9514821
TI  - Local administration of thyroid hormones in silicone chamber increases
      regeneration of rat transected sciatic nerve.
AB  - Conflicting actions of the exogenous thyroid hormone on regenerating peripheral
      nerve have been reported. These contradictory results were probably due to daily
      intraperitoneal injections which induce a high concentration of thyroid hormone
      after administration. In our present study we adapted a technique which allows a
      local administration of thyroid hormones in a closed system. The effect of a
      single and local treatment with triiodothyronine (T3) on axonal growth across a
      gap between sectioned ends of sciatic nerve within silicone chambers was examined
      in Wistar rats. After nerve transection and surgical implantation, silicone
      chambers were filled with either a neutral pH solution of triiodothyronine
      dissolved in NaOH or with sterile solvent as control. Regeneration of the nerves
      was examined 2 to 8 weeks following the surgery. Early regeneration (4 weeks) was
      studied by morphological analysis of nerves which showed a significant difference
      between T3-treated and control groups. Morphometric analysis revealed: (1) a
      significant difference in the mean diameter of myelinated axons between T3
      treated nerve (phi 3.80 +/- 0.22 microns) and control (phi 3.07 +/- 0.44
      microns); (2) that T3 increased significantly (1.4-fold) the number of myelinated
      axons that grew into the middle and distal ends of regeneration chambers; (3)
      that ultrastructural analysis showed significantly higher percentage of
      myelinated axons per total axon population in T3-treated groups (38.8 +/- 5.9%)
      as compared to control (16.0 +/- 2.3%); and (4) that the myelinated axons had
      thicker myelin sheaths. The beneficial effects of T3 on regeneration, observed at
      4 weeks, were sustained over a prolonged period of time. Thus, at 8 weeks of
      regeneration, the number, the mean diameter of myelinated axons, and the
      thickness of myelin sheaths remained significantly greater in T3-treated groups.
      Therefore, a single and local administration of thyroid hormone at the level of
      the transected sciatic nerve is sufficient to rapidly set off several mechanisms
      which, in turn, produce a stimulating and lasting effect on peripheral nerve
      regeneration. The beneficial effects of T3 upon injured peripheral nerve may have
      considerable therapeutic potential.

PMID- 9514822
TI  - Colchicine differentially induces the expressions of nitric oxide synthases in
      central and peripheral catecholaminergic neurons.
AB  - This study was aimed at elucidating differences in nerve injury induced
      expression of nitric oxide synthases (NOS) between the peripheral and central
      catecholaminergic neurons. Colchicine was used to disrupt chemically the neuronal
      cytoskeletal integrity. A marked increase in the expression of neuronal NOS-IR
      and NADPH-diaphorase activity, a marker of neuronal NOS (nNOS), was seen in
      distinct populations of post-ganglionic sympathetic neurons of the superior
      cervical ganglion after intraganglionic colchicine injection. Similarly,
      immunoreactivity for the inducible form of NOS (iNOS) was induced in some
      sympathetic neuron somata. However, this immunoreactivity did not coincide with
      nNOS-IR. In contrast to the sympathetic neurons, hypothalamic arcuate and
      periventricular dopaminergic neurons did not show NOS-IR or NADPH-DA either in
      intact animals or in animals treated with an intracerebroventricular injection of
      colchicine. Immunoreactivity for the inducible form of NOS revealed no neuronal
      staining in the hypothalamic neurons in either group, while a large number of
      glia-resembling cells around the third ventricle showed slight expression of iNOS
      IR. The present results show that expression of both neuronal and inducible forms
      of NOS may be induced by colchicine in some catecholaminergic neurons. It is
      suggested that these inductions are specific to certain catecholaminergic
      neuronal systems, like the sympathetic neurons, rather than a general property of
      catecholaminergic neurons.

PMID- 9514823
TI  - Extent of nociceptive dermatomes in adult rats is not primarily maintained by
      axonal competition.
AB  - Nociceptive innervation territories of individual peripheral and spinal nerves in
      the skin of the rat hind paw were investigated. In addition, the hypothesis that
      competitive interactions among the axons from adjacent dorsal root ganglia (DRG)
      play an important role in maintenance of dermatomal extent in adult animals was
      tested. The area of innervation territories of individual spinal and peripheral
      nerves was determined by nociceptive pinch test of the skin after extirpation of
      adjacent DRGs or transection of adjacent peripheral nerves, respectively.
      Positions of nociceptive dermatomes and innervation territories of peripheral
      nerves were similar to the territories innervated by the C-fibers described
      earlier by dye extravasation technique. In contrast, our results convincingly
      demonstrated substantial overlap of nociceptive (probably A delta) fibers from
      adjacent dermatomes in which the autonomous innervation areas were only about one
      half of the maximal areas. Nociceptive territories of peripheral nerves
      overlapped, too. Accordingly, we could find no autonomous innervation area of the
      sural nerve. Two weeks after extirpation of adjacent DRGs, the area of each of
      the isolated dermatomes L3, L4, and L5 increased only by about 10%, and it did
      not change detectably during the next 6 months. The results of our study (a)
      support the view that innervation fields supplied by the nociceptive (probably A
      delta) fibers are greater and display more overlap than those supplied by the C
      fibers of the same nerve and (b) suggest that axonal competition for innervation
      territory is not decisive for maintenance of dermatomal borders in the adult rat.

PMID- 9514824
TI  - Characteristics of the in vitro vasoactivity of beta-amyloid peptides.
AB  - The beta-amyloid (A beta 1-40) peptide has previously been shown to enhance
      phenylephrine contraction of aortic rings in vitro. We have employed a novel
      observation, that A beta peptides enhance endothelin-1 (ET-1) contraction, to
      examine the relationship between vasoactivity and potential amyloidogenicity of A
      beta peptides, the role played by free radicals and calcium in the vasoactive
      mechanism, and the requirement of an intact endothelial layer for enhancement of
      vasoactivity. Rings of rat aortae were constricted with ET-1 before and after
      addition of amyloid peptide and/or other compounds, and a comparison was made
      between post- and pre-treatment contractions. In this system, vessel constriction
      is consistently dramatically enhanced by A beta 1-40, is enhanced less so by A
      beta 1-42, and is not enhanced by A beta 25-35. The endothelium is not required
      for A beta vasoactivity, and calcium channel blockers have a greater effect than
      antioxidants in blocking enhancement of vasoconstriction by A beta peptides. In
      contrast to A beta-induced cytotoxicity, A beta-induced vasoactivity is
      immediate, occurs in response to low doses of freshly solubilized peptide, and
      appears to be inversely related to the amyloidogenic potential of the A beta
      peptides. We conclude that the mechanism of A beta vasoactivity is distinct from
      that of A beta cytotoxicity. Although free radicals appear to modulate the
      vasoactive effects, the lack of requirement for endothelium suggests that loss of
      the free radical balance (between NO and O2-) may be a secondary influence on A
      beta enhancement of vasoconstriction. These effects of A beta on isolated
      vessels, and reported effects of A beta in cells of the vasculature, suggest that
      A beta-induced disruption of vascular tone may be a factor in the pathogenesis of
      cerebral amyloid angiopathy and Alzheimer's disease. Although the mechanism of
      enhanced vasoconstriction is unknown, it is reasonable to propose that in vivo
      contact of A beta peptides with small cerebral vessels may increase their
      tendency to constrict and oppose their tendency to relax. The subclinical
      ischemia resulting from this would be expected to up-regulate beta APP production
      in and around the vasculature with further increase in A beta formation and
      deposition. The disruptive and degenerative effects of such a cycle would lead to
      the complete destruction of cerebral vessels and consequently neuronal
      degeneration in the affected areas.

PMID- 9514825
TI  - Developmental patterns of BCL-2 and BCL-X polypeptide expression in the human
      spinal cord.
AB  - The cell death suppressors bcl-2 and bcl-x are developmentally regulated and may
      modulate physiologic cell death in the central nervous system (CNS). However,
      little data are currently available on the expression patterns of these
      polypeptides in the human CNS. We examined the ontogeny of bcl-2 and bcl-x in 12
      human spinal cords of gestational ages (GA) between 5 and 39 weeks and in 3 adult
      cords. Paraffin sections were probed by immunohistochemistry using well
      characterized, commercially available antibodies that had been raised against
      poorly conserved epitopes of these homologous proteins. Between 5 and 10 weeks
      GA, bcl-2 immunoreactivity was identified in primitive neuroepithelial cells of
      the ventricular zone. Individual cells of the mantle zone were stained including
      clusters of early anterior horn cells. Bcl-x immunoreactivity was most prominent
      in differentiating neurons of the mantle zone and less pronounced in the
      ventricular zone. Between 10 and 14 weeks GA, bcl-2 staining was observed in
      cells lining the central canal, neurons of the dorsal horn (especially laminae I
      and II), and in anterior horn cells. The latter exhibited a range of staining
      intensities from moderate to nondetectable. Bcl-2 immunoreactivity became
      markedly reduced between 15 and 25 weeks GA, persisting only in ependymal cells.
      In contrast, strong bcl-x staining was observed in most neurons throughout
      development and into adulthood. The period of apparent bcl-2 down-regulation
      overlaps with a peak in physiologic motoneuron death and the establishment of
      functional neuromuscular synapses in the human spinal cord. These findings
      suggest that bcl-2 and bcl-x may both be required for survival of early
      postmitotic neurons before appropriate synaptic connections have been
      established. Continued neuronal survival (after bcl-2 is down-regulated) may
      require persistent bcl-x expression in addition to target-derived neurotrophic
      factors made available through the formation of appropriate synapses.

PMID- 9514826
TI  - Lysosomal dysfunction reduces brain-derived neurotrophic factor expression.
AB  - Brain-derived neurotrophic factor (BDNF) expression in hippocampus and cortex is
      considerably reduced in Alzheimer's disease. The present study tested if
      lysosomal disturbances, a concomitant of brain aging, impair basal and/or induced
      expression of BDNF. Cultured hippocampal slices were incubated with N- CBZ-L
      phenylalanyl-L-alanine-diazomethylketone (ZPAD), an inhibitor of cathepsins B and
      L, for 6 days and processed for in situ hybridization using radiolabeled cRNA
      probes against BDNF mRNA. Multiple densitometric readings were collected from
      each of the three principal hippocampal subdivisions. Within-slice averages were
      substantially lower in the ZPAD-treated group compared to controls. Treatment
      with the inhibitor did not change average neuron diameter or packing density.
      Intense stimulation of glutamate receptors with kainate for 30 min (followed by a
      90-min recovery period) caused a nearly threefold increase in BDNF mRNA
      concentrations in the dentate gyrus while having only marginal effects in the
      other subdivisions. Slice averages of ZPAD-exposed cultures treated with kainate
      were lower than those of controls exposed to the excitotoxin; however, on a
      percentage basis, the kainate-induced increase in the dentate gyrus was
      comparable for the two groups (175 +/- 31 vs 179 +/- 39%). Kainate for 1 h (with
      a 5-h recovery) affected BDNF mRNA in a manner similar to that found with shorter
      infusions, i.e., induction in stratum granulosum but not elsewhere, lower overall
      slice averages with ZPAD treatment, and no evidence that ZPAD blocked the
      percentage increase in the dentate gyrus. These results provide evidence that
      lysosomal dysfunction occurring during brain aging could disrupt ongoing BDNF
      production without substantially impairing the neurotrophin response to intense
      physiological activity. The first observation suggests a plausible aging sequence
      leading to pathology while the second may be of interest with regard to possible
      therapeutics.

PMID- 9514827
TI  - Comparison of more and less lipophilic serotonin (5HT1B/1D) agonists in a model
      of trigeminovascular nociception in cat.
AB  - The trigeminovascular system consists of bipolar neurons innervating pain
      producing intracranial structures, such as the superior sagittal sinus (SSS), and
      projecting to the medullary and upper cervical dorsal horn second order neurons.
      Zolmitriptan is a newly developed 5HT1B/1D receptor agonist with both peripheral
      and central sites of action in the trigeminovascular system due to greater
      lipophilicity relative to the more hydrophilic antimigraine compound sumatriptan.
      Given that we have seen electrophysiological and autoradiographic binding data to
      suggest that the compound may inhibit activity at second-order neurons this study
      was designed to examine whether such an effect could be demonstrated in a
      population of trigeminal neurons using Fos immunohistochemistry. Cats were
      anesthetised with alpha-chloralose (60 mg/kg intraperitoneal then 20 mg/kg
      intravenous maintenance) with all surgery being conducted using halothane (1-3%).
      The animals were prepared for physiological monitoring, including blood pressure,
      heart rate, rectal temperature, and end-expiratory CO2. They were intubated,
      ventilated, and paralyzed with gallamine triethiodide (6 mg/kg i.v.). A midline
      craniotomy was performed to expose the sinus for electrical stimulation using
      hook electrodes. Twenty-four hours after completion of the surgical procedures
      the animal was ready for treatment. Vehicle, sumatriptan (85 micrograms/kg), or
      zolmitriptan (30 micrograms/kg) was administered and the SSS was stimulated (250
      microseconds, 100 V at 0.3 Hz) for 1 h. Following an additional 1 h the animal
      was perfused and immunohistochemistry was used to detect the protein product of
      the immediate early gene c-Fos. We compared the dorsal horns of the medulla
      (trigeminal nucleus caudalis) and the C1 and C2 cervical spinal cords in control
      animals with those receiving zolmitriptan or sumatriptan. We noted a significant
      reduction in Fos expression after treatment with zolmitriptan but no effect with
      sumatriptan. Given that zolmitriptan accesses central neurons and that the method
      of stimulation we have employed would bypass peripheral trigeminal mechanisms it
      is likely that the reduction in second-order trigeminal neuronal activity was due
      to a direct inhibitory effect of the compound on those cells. These neurons form
      a possible site for the treatment of acute attacks of migraine.

PMID- 9514829
TI  - nNOS expressing neurons in the entorhinal cortex and hippocampus are affected in
      patients with Alzheimer's disease.
AB  - Nitric oxide is a multifunctional molecule that acts as messenger/modulator in
      synaptogenesis and potential neurotoxin and is synthesized by three isozymes of
      Nitric oxide synthase (NOS). The role of NOS in Alzheimer's disease (AD) is
      unclear. For example, neurons in the entorhinal cortex (EC) that are highly
      vulnerable to neurodegeneration in AD express low levels of NOS and while it has
      been suggested that the inducible form of NOS is upregulated in AD, it is still
      not clear if the constitutive expressed isozyme (nNOS) is involved in the process
      of neurodegeneration. In order to better understand the role of nNOS in the
      pathogenesis of AD, sections from the EC and hippocampus (HC) of AD and control
      cases were immunohistochemically analyzed by single- and double-immunolabeling
      using antibodies against nNOS and PHF-tau. Semiquantitative assessment of numbers
      of nNOS expressing neurons in different areas of the HC and EC showed a
      remarkable loss of nNOS expressing neurons in the entorhinal cortex layer II and-
      less severe--CA1 and CA3 of the hippocampus in patients with AD. In addition,
      double-immunolabeling studies revealed that nNOS is strongly associated with
      neurofibrillary tangles and plaques. These findings indicate that nNOS expressing
      neurons are highly susceptible to neurodegeneration and that nNOS might
      contribute to the pathogenesis of AD.

PMID- 9514828
TI  - Increased peroxidation and reduced antioxidant enzyme activity in Alzheimer's
      disease.
AB  - The overall peroxidation activity in brain tissue by region from patients with
      Alzheimer's disease (AD) and age-matched controls was determined employing the
      thiobarbituric acid-reactive substances (TBARS) assay, a measure of lipid
      peroxidation, followed by a determination the activities of the antioxidant
      enzymes Cu/Zn superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and
      catalase (CAT), in the frontal, temporal, and cerebellar cortex of 10 AD and 9
      control brains. The level of TBARS was elevated in all regions, with particular
      statistical significance in the temporal cortex when compared to age-matched
      controls. SOD activity was significantly decreased in AD frontal and AD temporal
      cortex, while catalase activity was significantly decreased in AD temporal
      cortex. There was no significant difference in GSH-Px activity found in any of
      the regions examined. This study supports the theory that in AD the brain is
      affected by increased oxidative stress which, when combined with a decrease in
      SOD activity, produces oxidative alterations, seen most significantly in temporal
      cortex in AD, where the pathophysiologic changes are most severe.

PMID- 9514830
TI  - Neural heme oxygenase-1 expression in idiopathic Parkinson's disease.
AB  - Heme oxygenase-1 is a cellular stress protein expressed in brain and other
      tissues in response to oxidative challenge and other noxious stimuli. In the
      present study, immunohistochemistry was used to assess HO-1 expression in various
      postmortem human brain specimens derived from PD and control subjects. In the
      substantia nigra of both PD and control specimens, moderate HO-1 immunoreactivity
      was consistently observed in neuromelanin-containing (dopaminergic) neurons. Lewy
      bodies in PD nigra neurons exhibited intense HO-1 immunostaining in their
      peripheries. In both PD and control specimens, neuronal HO-1 staining was faint
      or nondetectable in the other brain regions surveyed. The fraction of GFAP
      positive astroglia expressing HO-1 in PD substantia nigra (77.1 +/- 12.3) was
      significantly greater than that observed in the substantia nigra of control
      subjects (18.7 +/- 7.1; P = 0.0015). In the other regions examined, percentages
      of GFAP-positive astroglia coexpressing HO-1 were relatively low and did not
      differ significantly (P > 0.05) between control and PD specimens. Upregulation of
      HO-1 in the substantia nigra of PD subjects supports the view that the affected
      tissue is experiencing chronic oxidative stress. In addition, excessive cellular
      levels of heme-derived free iron and carbon monoxide resulting from HO-1
      overactivity may contribute to the pathogenesis of PD.

PMID- 9514831
TI  - Gene transfer to rodent brain with recombinant adenoviral vectors: effects of
      infusion parameters, infectious titer, and virus concentration on transduction
      volume.
AB  - Initial studies examining intraparenchymal injection of recombinant viral vectors
      in rodent brain have demonstrated a limited region of gene transfer. We examined,
      independently, different infusion parameters to determine if the volume of cells
      transduced acutely could be increased. Varying the rate of infusion from 0.3 to 3
      microliters/min at constant time and virus dose did not improve the volume of
      brain transduced, with the lowest rate of infusion demonstrating the least amount
      of gene transfer. However, transduction volume did increase with increasing
      particle concentrations of virus, although the improvements were modest from 3 to
      9 x 10(9) total particles infused. Infusion of virus under conditions of
      hypertonicity resulted in modest improvements in the final transduced volume.
      These studies suggest that most changes in infusion parameters will have small
      effects on the initial transduction volume in rodent brain.

PMID- 9514832
TI  - Acute hypertension promotes hemorrhagic transformation in a rabbit embolic stroke
      model: effect of labetalol.
AB  - We examined the relationship between acute hypertension following cerebral
      embolization and subsequent hemorrhagic transformation (HT) in a rabbit embolic
      stroke model. We have shown previously that the likelihood and severity of
      hemorrhage were significantly correlated with the magnitude of an acute
      hypertensive response to embolization. It was not clear, however, whether
      hypertension actually caused hemorrhage or was merely a marker of more severe
      stroke. In the current studies, we attempted to clarify the relationship between
      acute hypertension and HT by either pharmacologically inducing or attenuating the
      brief hypertensive response to embolization in rabbits. Under halothane
      anesthesia, two catheters were implanted in the right carotid arteries of male
      New Zealand white rabbits, one oriented toward the heart and one toward the
      brain. The animals were allowed to awaken and were embolized using blood clot
      emboli injected into the middle cerebral artery. Blood pressure was monitored via
      the second carotid catheter. In the first experiment, hypertension was induced
      with angiotensin II, administered at the time of embolization or 1 h later. In
      the second experiment, we attempted to attenuate the hypertensive response using
      intravenous labetalol. The animals were sacrificed 18 h after embolization and
      the brains evaluated for hemorrhage. In the first experiment, administration of
      angiotensin II immediately after embolization did not increase the hypertensive
      response to embolization further than that spontaneously occurring, and no
      angiotensin II-related HT was observed. In contrast, an additional angiotensin-II
      induced hypertensive episode 1 h after embolization significantly increased the
      number of 5-mm serial brain sections displaying HT, from 3.0 +/- .3 (mean +/- SE)
      in Controls to 5.4 +/- .8 in treated animals. In the second experiment,
      administration of labetalol (15 mg/kg) significantly reduced the number of brain
      sections with visible HT, from 3.2 +/- .5 in controls to 1.6 +/- .4 in treated
      animals. Acute hypertension during the first hour after cerebral embolization
      promotes HT in this rabbit embolic stroke model. Labetalol prevents blood
      pressure elevation and reduces the extent of HT in the same model.

PMID- 9514833
TI  - Quantitative assessment of respiratory function following contusion injury of the
      cervical spinal cord.
AB  - In this study, we describe a new method for quantitative assessment of phrenic
      inspiratory motor activity in two models of cervical spinal cord contusion
      injury. Anesthetized rats received contusion injury either to the descending
      bulbospinal respiratory pathway on one side of the spinal cord alone (C2
      lateralized contusion) or to both the descending pathway, as well as the phrenic
      motoneuron pool bilaterally (C4/C5 midline contusion). Following injury,
      respiratory-associated phrenic nerve motor activity was recorded under
      standardized and then asphyxic conditions. Phrenic nerve efferent activity was
      rectified, integrated, and quantitated by determining the mean area under the
      integrated neurograms. The mean integrated area of the four inspiratory bursts
      recorded just before turning off the ventilator (to induce asphyxia) was
      determined and divided by the integrated area under the single largest
      respiratory burst recorded during asphyxia. This latter value was taken as the
      maximal inspiratory motor response that the rat was capable of generating during
      respiratory stress. Thus, a percentage of the maximal inspiratory motor drive was
      established for breathing in control and injured rats under standardized
      conditions. The results indicate that noninjured rats use 52 +/- 1.8% of maximal
      inspiratory motor drive under standardized conditions. In C2-contused rats, the
      results showed that while the percentage of maximal inspiratory motor drive on
      the noncontused side was similar to the control (55 +/- 4.1%), it was increased
      on the contused side (78 +/- 2.6%). In C4/5 lesions, the results indicate that
      this percentage was increased on both sides (77 +/- 4.4%). The results show the
      feasibility for performing quantitative evaluation of respiratory dysfunction in
      an animal model of cervical contusion injury. These findings lend to further
      development of this model for investigations of neuroplasticity and/or
      therapeutic interventions directed at ameliorating respiratory compromise
      following cervical spinal cord trauma.

PMID- 9514834
TI  - The spatial patterns of Lewy bodies, senile plaques, and neurofibrillary tangles
      in dementia with Lewy bodies.
AB  - The spatial patterns of Lewy bodies (LB), senile plaques (SP), and
      neurofibrillary tangles (NFT) were studied in ubiquitin-stained sections of the
      temporal lobe in cases of dementia with Lewy bodies (DLB), which varied in the
      degree of associated Alzheimer's disease (AD) pathology. In all patients, LB, SP,
      and NFT developed in clusters and in a significant proportion of brain areas, the
      clusters exhibited a regular periodicity parallel to the tissue boundary. In the
      lateral occipitotemporal gyrus (LOT) and parahippocampal gyrus (PHG), the
      clusters of LB were larger than those of the SP and NFT but in the hippocampus,
      clusters of the three lesions were of similar size. Mean cluster size of the LB,
      SP, and NFT was similar in cases of DLB with and without significant associated
      AD pathology. LB density was positively correlated with SP and NFT density in 42
      and 17% of brain areas analyzed, respectively, while SP and NFT densities were
      positively correlated in 7% of brain areas. The data suggest that LB in DLB
      exhibit similar spatial patterns to SP and NFT in AD and that SP and NFT exhibit
      similar spatial patterns in DLB and AD. In addition, in some instances, clusters
      of LB appeared to be more closely related spatially to the clusters of SP than to
      NFT.

PMID- 9514835
TI  - Role of glutamate receptor-mediated excitotoxicity in bilirubin-induced brain
      injury in the Gunn rat model.
AB  - Severe hyperbilirubinemia in neonates with prematurity and/or systemic illnesses
      such as hemolytic disease, acidosis, and hypoxemia enhances their risk for
      developing cerebral palsy, paralysis of ocular upgaze, and deafness. This
      neurologic syndrome has been associated with selective neuronal vulnerability in
      the basal ganglia, certain brainstem nuclei, and Purkinje cells. However, the
      mechanism by which bilirubin damages neurons remains unclear. In these studies,
      we found that intracerebral injection of N-methyl-D-aspartate (NMDA), an
      excitotoxic analogue of glutamate, caused greater injury in jaundiced 7-day-old
      Gunn (jj) rat pups than in nonjaundiced heterozygous (Nj) littermate controls.
      NMDA injection caused even greater injury when protein-bound bilirubin was
      displaced with the sulfonamide drug sulfadimethoxine in jaundiced homozygous
      pups. In additional experiments, the acute signs of bilirubin-mediated neuronal
      injury, induced in homozygous (jj) Gunn rats by treatment with sulfonamide, were
      reduced by concurrent treatment with the NMDA-type glutamate channel antagonist
      (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohept-5,10-imine (MK-801,
      dizocilpine). The results suggest that bilirubin may cause encephalopathy and
      neuronal injury, at least in part, through an NMDA receptor-mediated excitotoxic
      mechanism. This conclusion is consistent with clinical observations that
      bilirubin encephalopathy is synergistically worsened by hypoxemia, which also
      shares an excitotoxic mechanism of neuronal injury.

PMID- 9514836
TI  - Differential effects of anoxia and glutamate on cultured neocortical neurons.
AB  - That glutamate increases in the extracellular space of the brain during hypoxia
      or ischemia and that this amino acid, in high enough concentrations, kills
      neurons has led investigators to use glutamate and study the mechanisms
      underlying neuronal excitotoxicity as a model for acute cell death that occurs
      with low oxygen. However, there is some evidence that increased glutamate, on the
      one hand, and anoxia, on the other, may not be similar events. In this study we
      undertook experiments to determine whether glutamate, at various concentrations
      (20-500 microM), and anoxia induce similar changes in intracellular Ca2+ and in
      cell morphology as assessed by cell volume and eccentricity (degree of some
      ellipsoid shape). We found that glutamate was much more rapid in inducing a rise
      in Cai2+ and that the rise itself occurred at a faster rate than during anoxia.
      Anoxia produced more marked changes in cell volume and eccentricity. These
      results, which show major differences between glutamate and anoxia, indicate that
      while glutamate may play an important role in anoxic brain injury, glutamate
      excitotoxicity should not be used to mimic the effects of anoxia on nerve and
      brain function.

PMID- 9514837
TI  - Developmental changes in growth factors released by the embryonic inner ear.
AB  - Recent studies have demonstrated a role for neurotrophins in regulating the
      survival of developing auditory and vestibular neurons. However, the
      developmental time-course for neurotrophin production and release by inner ear
      tissues has not been defined. In the present study, neurotrophin-like activity
      was evaluated from culture medium conditioned by early- or midembryonic stage
      inner ears. Examination of the proteinaceous properties of conditioned medium
      revealed a developmental change in growth factor release by the inner ear.
      Neurotrophin-like molecules were not detected in medium conditioned by early
      stage otocysts. In contrast, neurotrophin-like bioactivity was detected in medium
      conditioned by middevelopmental stage inner ears. Western blot analysis revealed
      that NT-3 was released by the rat inner ear at midstages of inner ear
      development. ELISA measurements revealed that both NT-3 and BDNF are produced by
      the middevelopmental stage inner ear, and that NT-3 protein levels are higher
      than BDNF levels. These results suggest that there are developmental changes in
      the release of growth factors by the inner ear.

PMID- 9514838
TI  - MEETING ANNOUNCEMENT
AB  - Copyright

PMID- 9514839
TI  - ANNOUNCEMENT
AB  - Copyright

PMID- 9514840
TI  - Development and control of the circadian pacemaker for melatonin release in the
      chicken pineal gland.
AB  - Melatonin (MT) release from explanted pineal glands of 3- to 20-week-old chicken
      was investigated in a 5-day perifusion system. Both the chicken and the explanted
      glands were exposed to various environmental lighting regimens. OBSERVATIONS: (1)
      The explanted chicken pineal is sensitive to direct light. Continuous
      illumination during the in vitro period abolishes the circadian rhythm of the MT
      secretion in 3 days. Continuous darkness has limited effect. (2) Reverse
      illumination completely reverses the MT cycle in 2 days. (3) Rhythmic
      illumination with short (6-h) periods only slightly modulates the MT release
      pattern: the basic, 24-h periodicity is preserved. (4) The circadian MT pacemaker
      develops normally and becomes synchronized to the day even if the chicken has
      never experienced alteration in the environmental illumination (those hatched and
      bred under continuous illumination). The explanted pineal from these chickens
      exhibits normal MT cycle and light sensitivity. Conclusion, Chicken pineal
      contains a complete, genetically coded circadian pacemaker with a fixed
      frequency. The pacemaker is synchronized to the day by the altered environmental
      illumination and by at least one other, unknown environmental factor. With
      altered illumination, in vitro, the 24-h periodicity of the pacemaker cannot be
      changed significantly, but its phase can be shifted. In contrast to conclusions
      obtained from in vivo observation in mammals, light seems to stimulate MT
      secretion from the avian pineal in vitro. For development and daily
      synchronization of the circadian MT pacemaker in the chicken pineal gland,
      periodic changes in the environmental illumination are not necessary.

PMID- 9514841
TI  - Localization and partial characterization of melatonin receptors in amphioxus,
      hagfish, lamprey, and skate.
AB  - Through its secretion of melatonin, the pineal complex of vertebrates exerts a
      range of physiological effects including regulation of circadian rhythms,
      seasonal reproduction, metamorphosis, and body color change. Little is known
      about phylogenetic differences in the distribution and characteristics of
      melatonin binding sites in fishes. We used in vitro autoradiography to examine
      binding of [2-125I]iodomelatonin (IMEL) in 20-micron frozen sections of amphioxus
      (Branchiostoma lanceolatum), Atlantic hagfish (Myxine glutinosa), larval and
      adult lamprey (Petromyzon marinus), little skate (Raja erinacea), and rainbow
      trout (Oncorhynchus mykiss). Tissue was incubated with IMEL in the presence or
      absence of unlabeled melatonin (1 muM, in order to assess nonspecific binding). A
      concentration of 32 pM IMEL was used for single point assays and competition
      studies. No specific binding was found in hagfish or amphioxus, which lack a
      pineal complex. In the optic tecta of lamprey, skate, and trout, IMEL binding is
      highly specific (melatonin >> N-acetylserotonin > 5- methoxytryptophol >>
      serotonin). Scatchard analysis revealed that the tectal binding sites are of high
      affinity (Kd = 36, 38, and 50 pM) and low capacity (Bmax = 8.1, 19.8, and 21.8
      fmol/mg protein) in lamprey, skate, and trout, respectively. In adult lampreys,
      intense specific IMEL binding is found in the optic tectum (layer I > II > III)
      and preoptic nucleus (pars parvocellularis > magnocellularis). Binding was less
      intense and consistent in the same areas of ammocoete brain. In skates and trout,
      intense specific binding is found in optic tectum, lateral geniculate body,
      diencephalic preoptic and suprachiasmatic nuclei, basal hypothalamus, and the
      medial pallium. These results indicate that specific melatonin binding sites are
      present in all craniate taxa examined except in hagfish. Although we cannot rule
      out the possibility that melatonin receptors are secondarily lost in hagfish,
      their absence in amphioxus makes this unlikely. We speculate that melatonin
      actions in early vertebrates may have included regulation of visual and endocrine
      responses to light.

PMID- 9514842
TI  - Specific binding sites for [3H]Dexamethasone in the hypothalamus of juvenile
      rainbow trout, Oncorhynchus mykiss.
AB  - Indirect evidence suggests that glucocorticoid hormones may act through cellular
      receptors to play a neuromodulatory role in the teleost CNS. We now report our
      findings on the use of [3H]dexamethasone (DEX) to identify hypothalamic
      glucocorticoid receptors (GRs) in juvenile rainbow trout, Oncorhynchus mykiss.
      Hypothalamic cytosol was incubated with [3H]DEX under various experimental
      paradigms with incubations terminated by addition of dextran-coated charcoal;
      following immediate centrifugation, a sample of bound [3H]DEX (supernatant) was
      collected and assessed for 3 H content. [3H]DEX binding was tissue dependent
      between 0.5 and 2. 0 hypothalamus equivalents per tube (1.0 to 4.7 mg protein,
      respectively). Specific binding (BSP) increased with time for 1.5 h and remained
      relatively constant for an additional 2.5 h; the calculated association rate
      constant was 2.23 x 10(8) M-1 x min-1. Equilibrium BSP was dissociated by
      addition of a 5000 M excess cortisol with an accompaning t1/2 of 1.25 h and
      dissociation rate constant of 0.553 min-1. BSP was saturable with a calculated
      equilibrium Kd and BMAX of 1.22 nM and 296 fmol/mg protein, respectively. BSP was
      displaced under equilibrium conditions by the corticosteroids, but to a lesser
      extent by the mineralocorticoid, estrogen, and progestin. The rank order of
      potency for [3H]DEX displacement was DEX > cortisol >> corticosterone > m
      triamcinolone = 11-deoxycortisol >> aldosterone > progesterone >>> 17 beta
      estradiol. These properties of specifically bound [3H]DEX indicate the presence
      of a GR, similar to the mammalian cytosolic GR, in the hypothalamus of juvenile
      rainbow trout.

PMID- 9514843
TI  - FMRFamide-like immunoreactivity in the olfactory system responds to morphine
      treatment in the teleost Clarias batrachus: involvement of opiate receptors.
AB  - In view of the close relationship between the FMRF-related peptides and the
      central opiate-sensitive system, we investigated the effects of morphine, alone
      and in combination with naloxone, on the FMRFamide-like immunoreactivity in the
      olfactory system of the teleost, Clarias batrachus. In the olfactory system of
      normal and untreated fish, FMRFamide-like immunoreactivity was confined to the
      ganglion cells and fibers of the terminal nerve; the cells in the olfactory
      epithelium per se or the olfactory nerve were not immunoreactive. Intensely
      immunoreactive cells appeared in the olfactory epithelium following 2 h of
      intracranial morphine administration. FMRFamide-like immunoreactivity also
      appeared in the olfactory nerve fibers as they ran caudally and arborized in the
      glomerular layer of the bulb. However, immunoreactivity in the ganglion cells of
      the terminal nerve and the ensuing fibers was abolished, suggesting the
      transport/release of the immunoreactive material. Pretreatment with naloxone, a
      potent opiate receptor antagonist, reversed the effects of morphine, suggesting
      the involvement of opiate receptors in the regulation of the ganglion cells of
      the terminal nerve. The results provide initial immunocytochemical evidence in
      favor of a relationship between the opiates and FMRFamide-containing systems
      within the framework of the olfactory system.

PMID- 9514844
TI  - Somatostatin inhibits (d-Arg6, Pro9-NEt) salmon gonadotropin-releasing hormone-
      and dopamine D1-stimulated growth hormone release from perifused pituitary cells
      of chinese grass carp, ctenopharyngodon idellus.
AB  - In this study, a heterologous radioimmunoassay (RIA) for grass carp GH has been
      validated and used to monitor the kinetics of GH release from perifused grass
      carp pituitary cells. To establish the anatomical specificity of GH antiserum
      used in this RIA, immunohistochemical staining was performed in grass carp
      pituitary sections. Somatotrophs recognized by this GH antiserum were located
      mainly in the proximal pars distalis without overlapping with gonadotrophs
      located in the same area or with lactotrophs located in the rostral pars
      distalis. The immunoreactivity of somatotrophs was abolished by preabsorbing GH
      antiserum with purified grass carp GH, suggesting that the possibility of a cross
      reactivity of antiserum with other grass carp pituitary hormones is unlikely.
      Using 125I-labeled carp GH as the RIA tracer, parallelism was observed among the
      displacement curves of grass carp GH standard, grass carp serum, and culture
      medium conditioned by grass carp pituitary cells, suggesting that this RIA can be
      used to quantitate grass carp GH levels in biological samples. Using an in vitro
      column perifusion system, a superactive gonadotropin-releasing hormone (GnRH)
      analog (d-Arg6, Pro9-NEt)-sGnRH(sGnRHa, 0.3-30 nM), dopamine (DA, 0.1-10 muM),
      and the nonselective DA agonist apomorphine (0.1-10 muM) stimulated GH release
      from grass carp pituitary cells in a dose-dependent manner. The GH-releasing
      effect of DA was mimicked by the D1 agonists SKF38393 (0.1-10 muM) and SKF77434
      (0.1-10 muM), but not by the D2 agonist LY171555 (3 muM). In addition, the GH
      response to DA (1 muM) was blocked by the D1 antagonist SCH23390 (5 muM) but not
      by the D2 antagonist (+/-) sulpiride (5 muM), suggesting that the GH-releasing
      action of DA is mediated through receptors resembling mammalian D1 receptors.
      Somatostatin-14 (SRIF14, 0.01-100 nM), unlike sGnRHa and DA, induced a dose
      dependent suppression on basal GH release. At a high dose (100 nM), SRIF14 also
      abolished the GH responses to sGnRHa (100 nM), DA (10 muM), and the D1 agonist
      SKF38393 (3 muM). These results, as a whole, provide evidence that GH release in
      the grass carp is under the direct regulation of GnRH, DA, and SRIF at the
      pituitary cell level. The present study also suggests that DA D1 receptors are
      present in grass carp pituitary cells mediating the GH-releasing action of DA.

PMID- 9514845
TI  - Peptide growth factors modulate prostaglandin E and F production by goldfish
      ovarian follicles.
AB  - This study examines the effect of epidermal growth factor (EGF) on prostaglandin
      synthesis by goldfish ovarian follicles at different developmental stages. Early
      vitellogenic follicles (EVIT), vitellogenic follicles (VIT), and prematurational
      full-grown follicles (PMFG) were examined. EGF alone had no effect on
      prostaglandin synthesis whereas production of PGE2 and PGF2alpha was enhanced in
      the presence of the eicosaniod precursor arachidonic acid (AA) in all three
      follicle classes. EGF enhanced AA stimulation of PGE2 production in both VIT and
      PMFG follicles. In the same follicles, AA-induced PGF2alpha production either was
      reduced or was unaffected by EGF. This suggests regulation of prostaglandin
      synthesis at a point downstream of the conversion of AA to PGH2: the precursor
      for both PGE2 and PGF2alpha. EGF had no effect on AA stimulation of either PGE2
      or PGF2alpha in EVIT follicles. While only VIT and PMFG follicles were responsive
      to EGF, Western blotting with an antibody to the human EGF-receptor (EGF-R)
      suggests that all three classes of follicle may possess the receptor protein.
      Additional tests showed that insulin-like growth factor-I (IGF-I) had no effect
      on the production of either PGE2 or PGF2alpha by PMFG follicles. By comparison
      both TGFalpha (which binds to the EGF receptor) and TGFbeta (which acts through a
      different receptor) enhanced AA-stimulated PGE2 production while having no effect
      on AA-stimulated PGF2alpha production. In summary, this study demonstrates that
      several growth factors (EGF, TGFalpha, TGFbeta) may play a role in the regulation
      of ovarian prostaglandin synthesis and that the actions of EGF change during
      ovarian follicular development in the goldfish.

PMID- 9514846
TI  - Immunocytochemical identification of two distinct gonadotropic cells (GTH I and
      GTH II) in the pituitary of bluefin tuna, Thunnus thynnus.
AB  - Immunocytochemical identification of GTH I and GTH II cells in the pituitary of
      the bluefin tuna (Thunnus thynnus) was performed using antisera specific for the
      common alpha-subunit and the two distinct beta-subunits of tuna (Thunnus obesus)
      GTH I and GTH II. Cells of the dorsal part of the proximal pars distalis (PPD),
      in close association with somatotrophs, displayed immunoreactivity of GTHIbeta.
      GTH IIbeta immunoreactivity was present in cells of the central part of the PPD
      and the external border of the pars intermedia. Anti-GTHalpha immunostained both
      GTH Ibeta- and GTH IIbeta-immunoreactive cells and also thyrotrophs. Both GTH
      Ibeta- and GTH IIbeta-immunoreactive cells were observed in immature bluefin
      tuna, although there were greater numbers of GTH IIbeta immunoreactive cells.
      These results suggest that GTH I and GTH II are synthesized in separate cells in
      the pituitary of the bluefin tuna. The localization and appearance of the two
      distinct gonadotropic cells of the tuna are compared with the salmonid
      arrangement.

PMID- 9514847
TI  - The parathyroid glands of two species of dolphin--Risso's dolphin, Grampus
      griseus, and bottlenose dolphin, Tursiops truncatus.
AB  - Although there have been many reports regarding the structure of the parathyroid
      glands of various terrestrial mammals, little is known about the parathyroid
      glands of marine mammals including Cetacea. The morphology of the parathyroid
      glands of three Risso's dolphins, Grampus griseus (about 3 m in length and 300 kg
      in weight), and three bottlenose dolphins, Tursiops truncatus (about 3 m in
      length and 300 kg in weight), was examined macroscopically and microscopically.
      The dolphins examined in the present study had two or four parathyroid glands
      that varied in size and location on the thyroid gland. Each parathyroid gland was
      encapsulated by fibrous tissue on the dorsal surface of the thyroid gland, and
      was divided into several lobules by interlobular connective tissue which
      contained numerous capillaries. The parenchymal cells consisted of pale staining
      chief cells. Each cell was polygonal and about 15 microm in diameter, and had one
      round or oval nucleus. Oxyphil cells were not found. Considering their greater
      body size, the parathyroid glands were rather small. By electron microscopic
      observation, the parathyroid gland of the bottlenose dolphin had sparse granular
      endoplasmic reticulum, poorly developed Golgi complexes, and abundant secretory
      granules in the cytoplasm of the chief cells. These results support a possibility
      that the activity of the parathyroid gland is suppressed to adapt to a sea
      habitat.

PMID- 9514849
TI  - David R. Idler (1923-1996).

PMID- 9514848
TI  - The effect of biogenic amines and their analogs on carbohydrate metabolism in the
      fat body of the cockroach Blaberus discoidalis.
AB  - Several biogenic amines and their analogs were examined for stimulatory effects
      on glycogen phosphorylase activity and trehalose biosynthesis in fat body of the
      cockroach, Blaberus discoidalis. Octopamine and synephrine were the most potent
      activators of fat body phosphorylase; 10 muM octopamine being nearly as effective
      as the hypertrehalosemic hormone (HTH). Epinephrine, norepinephrine, and tyramine
      produced intermediate effects, whereas dopamine, 5-hydroxytryptamine, and
      melatonin had no effect. The fat body octopamine receptors appeared to be
      pharmacologically related to vertebrate alpha-adrenergic receptors and belonged
      to the Octopamine1 class receptor. In contrast to previous reports, synephrine
      also induced both phosphorylase activation and hypertrehalosemia as effectively
      as octopamine. Demethylchlordimeform, a formamidine insecticide structurally
      similar to octopamine, also strongly activated fat body phosphorylase, possibly
      by interaction with the octopamine receptor.

PMID- 9514851
TI  - Glyphosate is an inhibitor of plant cytochrome P450: functional expression of
      Thlaspi arvensae cytochrome P45071B1/reductase fusion protein in Escherichia
      coli.
AB  - Glyphosate (Roundup) is an herbicide used extensively worldwide which acts as an
      inhibitor of 5'enolpyruvylshikimate-3-phosphate synthase and for which transgenic
      herbicide resistant plants have been developed. Here we report for the first time
      that glyphosate is an inhibitor of cytochrome P450 using a functional expression
      system for Thlaspi arvensae CYP71B1 in Escherichia coli. CYP71B1 was fused to the
      soluble domain of a plant cytochrome P450 reductase (CPR) from Catharanthus
      roseus. CYP71B1 could obtain reducing equivalents in this fusion construct and
      metabolised the polycyclic aromatic hydrocarbon, benzo(a)pyrene. The fusion
      protein retained normal spectral characteristics having a Soret peak at 448 nm in
      the reduced carbon monoxide difference spectrum. Addition of the herbicide
      resulted in a Type II spectrum indicative of binding via the nitrogen group to
      haem as a sixth ligand. A Ks of 60 microM was observed and an IC50 of 12 microM
      was observed for glyphosate inhibition of CYP71B1 activity. The implications of
      these results are discussed.

PMID- 9514852
TI  - Hydrocortisone reinforces the blood-brain barrier properties in a serum free cell
      culture system.
AB  - The increasing number of newly developed drugs demands for functional in vitro
      models of the blood-brain barrier to determine their brain uptake. Cultured
      cerebral capillary endothelial cells are considered to be such a model, however
      in serum containing media they exhibit low electrical resistances and high
      permeabilities compared to the in vivo situation. Here we report the
      establishment of a serum-free cell culture model. Withdrawal of serum already
      caused a twofold increase of transendothelial resistance (TER), which in presence
      of serum is about 100-150 omega.cm2. We tested several supplements and found that
      hydrocortisone is a potent stimulator for the formation of barrier properties.
      TERs up to 1000 omega.cm2 were measured in the presence of physiological relevant
      hydrocortisone concentrations. In correspondence to the TER increase
      hydrocortisone decreased cell monolayer permeability for sucrose down to 5 x 10(
      7) cm/s, which is close to the in vivo value of 1.2 x 10(-7) cm/s and by a factor
      of five lower compared to cultures without hydrocortisone and in presence of
      serum.

PMID- 9514853
TI  - A monoclonal antibody selected for probing the folding of staphylococcal nuclease
      and its N-terminal fragments.
AB  - Monoclonal antibody McAb2C9 against Staphylococcal nuclease (SNase R) and its N
      terminal fragments was produced and characterized. It was observed that the
      intact enzyme SNase R and its seven fragments (SNR141, SNR135, SNR121, SNR110,
      SNR102, SNR79 and SNR52) differed in their interactions with McAb2C9. However,
      the fragments with weak immunoreactivity, such as SNR141 and SNR110, increased
      ability reacting with McAb2C9 in their partially unfolded state. It suggests that
      the differences of immunoreactivity among the fragments are due to diverse extent
      of the exposure of the specific epitope and the conformation of the peptide
      fragment. The monoclonal antibody McAb2C9 could be a useful probe to investigate
      the mechanism of folding of SNase R and its N-terminal fragments.

PMID- 9514854
TI  - Molecular cloning of human testis mRNA specifically expressed in haploid germ
      cells, having structural homology with the A-kinase anchoring proteins.
AB  - We have cloned a human testis specific gene (hi), which encodes for a protein
      having regional homologies to the domain of A-kinase anchoring proteins. Open
      reading frame encodes a protein of 860 amino acids. The predicted protein has a
      molecular weight 95.8 kD and contains 32 cysteine residues and 34 potential
      phosphorylation sites. The deduced protein analysis revealed an eukaryotic
      secretory signal with a potential cleavage site. Northern blot analysis detected
      a single transcript of approximately 3.0 kb in testis and not in any other
      somatic tissues. Expression of hi transcript was observed only in round
      spermatids indicating post meiotic haploid gene expression.

PMID- 9514855
TI  - The role of calcium in the cell cycle: facts and hypotheses.
AB  - The regulation of cell cycle progression is a complex process which involves
      kinase cascades, protease action, production of second messengers and other
      operations. Increasing evidence now compellingly suggests that changes in the
      intracellular Ca2+ concentration may also have a crucial role. Ca2+ transients
      occur at the awakening from quiescence, at the G/S transition, during S-phase,
      and at the exit from mitosis. They may lead to the activation of Ca2+ binding
      proteins like S-100, but the key decoder of the Ca2+ signals in the cycle is
      calmodulin. Activation of calmodulin leads to the stimulation of protein kinases,
      i.e., CaM-kinase II, and of the CaM-dependent protein phosphatase calcineurin.
      Ample evidence now indicates the G/S transition, the progression from G2 to M,
      and the metaphase/anaphase transition as specific points of intervention of CaM
      kinase II. Another attractive possibility for the role of Ca2+ in the cycle is
      through the activation of the Ca(2+)-dependent protease calpain: other proteases
      (e.g., the proteasome) have been suggested to be responsible for the degradation
      of some of cyclins, which is essential to the progression of the cycle. One of
      the cyclins, however, (D1) is instead degraded by calpain, which has been shown
      to promote both mitosis and meiosis when injected into somatic cells or oocytes.

PMID- 9514856
TI  - Enhanced and specific gene expression via tissue-specific production of Cre
      recombinase using adenovirus vector.
AB  - A tissue-specific promoter is potentially valuable for the study of specific gene
      function and for gene therapy, as it permits a linked cytotoxic or any other gene
      to be expressed specifically in target cells. The expression levels of such
      promoters are generally low, and we have therefore developed a novel and general
      method to enhance the expression level of a tissue-specific promoter while
      maintaining specificity. We constructed a "regulator" recombinant adenovirus
      (rAd) producing the site-specific recombinase Cre under the control of the
      hepatocarcinoma-specific alpha-fetoprotein (AFP) promoter. The rAd was infected
      to AFP-producing cells together with a "target" rAd containing a Cre-activating
      potent expression unit. In in vitro experiments, the double infection method gave
      about 50-fold higher expression than the single rAd infection directly driven by
      the AFP promoter, while maintaining strict specificity to AFP-producing cells.
      The enhanced and specific expression was also observed in in vivo tumor models.
      This method may contribute not only to the establishment of specific gene
      therapies but also to basic study for elucidating cell-type specific gene
      functions.

PMID- 9514857
TI  - Identification of Schizosaccharomyces pombe prenol as dolichol-16,17.
AB  - The identity of the prenol involved in N-linked glycosylation in the fission
      yeast Schizosaccharomyces pombe was unknown. In order to determine the identity
      of the prenol, S. pombe cells were incubated with a metabolic precursor of
      prenol, tritiated mevalonolactone. The cells incorporated only a modest amount of
      label, about 1000 dpm per million cells, into base-stable lipid and only 1% of
      that radioactivity was incorporated into prenol. We found by normal phase silica
      HPLC and more directly by the lack of reactivity with MnO2 that the labeled lipid
      was predominantly dolichol, not polyprenol. Reverse phase HPLC demonstrated that
      in S. pombe dolichol ranged between 14 and 18 isoprene units with dolichol-16,17
      being the most abundant prenol. This dolichol is of an intermediate length,
      between the dolichol of S. cerevisiae and that of mammalian cells.

PMID- 9514858
TI  - The role of interhelical ionic interactions in myosin rod assembly.
AB  - Interhelical electrostatic interactions at specific heptad positions can regulate
      dimerization specificity of alpha-helical coiled-coils. We have analyzed 20
      vertebrate myosin sequences from a variety of organisms and tissues in order to
      determine if interhelical ionic interactions correlate with the observed myosin
      dimerization specificity. We find that the sites for potential interhelical ion
      pairing are identical in virtually all sarcomeric myosins whether they form homo-
      or heterodimers. We also show that smooth muscle and non-muscle myosin rod
      sequences exhibit a different conserved pattern of potential interhelical ion
      pairing. These observations suggest that myosin rod residues involved in
      interhelical electrostatic interactions do not regulate dimerization specificity,
      but may contribute to the specific arrangements of myosin molecules that
      determine differences in the filament morphology of sarcomeric and non-sarcomeric
      muscles.

PMID- 9514859
TI  - Oxidative stress in Staphylococcus aureus associated to the cleavage of an
      isoxazolylnaphthoquinoneimine with antibacterial capacity.
AB  - Staphylococcus aureus was inhibited by exposure to 2-hydroxy-N-(3,4-dimethyl-5
      isoxazolyl)-1,4-naphthoquinone-4-imine (Q1). This compound was cleavaged in the
      presence of bacteria and an efflux of isoxazolamine was detected whereas in the
      S. aureus membrane and cytoplasm was observed an absorption band similar to that
      of the bencenoid ring. Non-viable bacteria showed intact Q1 intracellularly and
      in the membrane. Antistaphylococcus effect was associated to Q1 interaction with
      the respiratory chain, the oxidative metabolites were stimulated; there was
      cellular injury simultaneous to reduction of antibiotic molecule and efflux of
      isoxazolamine. The bacteria treated with Q1 increased its oxygen consumption and
      superoxide anion generation. Superoxide dismutase (SOD) production was
      stimulated, but it was principally extracellular in S. aureus. Escherichia coli,
      a species resistant to the antibiotic, did not reduce Q1 and showed lower
      superoxide anion generation; besides, there was an increase of intracellular SOD
      with extracellular decrease.

PMID- 9514860
TI  - The Dictyostelium MAP kinase DdERK2 functions as a cytosolic protein in complexes
      with its potential substrates in chemotactic signal transduction.
AB  - A polyclonal antibody against a MAP kinase (DdERK2) in Dictyostelium has been
      made and used to study DdERK2 activation and localization. The activation of
      DdERK2 by the chemoattractants cAMP and folate is rapid and transient. Its
      activity peaks between 15 and 60 seconds after cAMP stimulation and declines to
      basal levels after 5 minutes. In parallel with the DdERK2 activation is the
      appearance of a higher mobility band on Western blots. An antibody specific for
      activated MAP kinase shows that only the shifted band is tyrosine phosphorylated,
      suggesting that it is the active form. Both unstimulated and stimulated DdERK2
      are soluble. In vitro phosphorylation with cell lysate supernatants or
      immunoprecipitates demonstrates the presence of several potential substrates, as
      identified by SDS-PAGE with mobility corresponding to molecular weights of 150,
      25, and 19 kDa. Furthermore, immunoprecipitation studies suggest that these
      substrates are in a complex with DdERK2. These data suggest that DdERK2 works via
      cytoplasmic proteins to mediate signaling responses in Dictyostelium.

PMID- 9514861
TI  - Genetic analysis on the NifW by utilizing the yeast two-hybrid system revealed
      that the NifW of Azotobacter vinelandii interacts with the NifZ to form higher
      order complexes.
AB  - Nitrogenase is a complex metalloenzyme composed of two separately purified
      proteins designated the Fe-protein and the MoFe-protein. Apart from these two
      proteins, a number of accessory proteins are essential for the maturation and
      assembly of nitrogenase. Even though experimental evidence suggests that these
      accessory proteins are required for nitrogenase activity, the exact roles played
      by many of these proteins in the functions of nitrogenase are unclear. Our
      studies were directed to understand the role of two nif accessory proteins, the
      NifW and the NifZ in the biological nitrogen fixation. To accomplish this, we
      have utilized a genetic method, the Yeast based Two-Hybrid protein-protein
      interaction assay. This analysis showed that the NifW could interact with itself
      to make a multimeric complex. In contrast, the NifZ could not interact with
      itself. However, the NifZ could interact with the NifW. Previously it was shown
      that mutating either the NifW or the NifZ have similar effects on the activity of
      nitrogenase. This observation indicated that both these proteins may exert their
      regulation on the nitrogenase by a common pathway. Furthermore, it was suggested
      that the NifW plays a role in the oxygen-protection of the MoFe-protein by direct
      physical interaction. Our observation that the NifW can interact with itself as
      well as with the NifZ, suggests that the NifW and the NifZ may form a higher
      order complex and such a complex may be needed to exert the effects of the NifW
      or the NifZ on the nitrogenase activity.

PMID- 9514862
TI  - The airway-epithelium: a novel site of action by guanylin.
AB  - We studied the activation of a chloride channel in normal human bronchial
      epithelial cells (NHBE) by guanylin. We have observed a background Cl current
      (ICl,background) and a guanylin-induced outward rectifying chloride currents
      (ORCC) in NHBE. ICl,background was present in 93% of cells (n = 114), was
      outwardly-rectifying, and could be completely blocked by 100 microM NPPB (5-Nitro
      2(3-phenyl-propylamino)-benzoic acid. Activation of cAMP-activated Cl current
      with 200 microM CPT-cAMP (8-(4-Chlorophenylthio) adenosine-3',5'-monophosphate)
      occurred in only 35.3% of cells (n = 34). Gyanylin activated an ORCC in 78.6% (n
      = 11) of cells. Gyanylin also induced chloride currents in cells that had failed
      to respond to CPT-cAMP (n = 5). Both CPT-cAMP and the guanylin-induced chloride
      currents showed strong outward rectification. 500 microM DIDS (4,4'
      diisothiocyanostibene-2,2'-disulfonic acid) blocked the guanylin-induced ORCC (n
      = 10). CONCLUSION: Guanylin activates a DIDS-sensitive ORCC in the NHBE cell
      which is only modestly activated by cAMP. The guanylin receptor in the NHBE might
      be of major importance in the regulation of chloride channel activity and
      transepithelial fluid transport in normal and abnormal airways.

PMID- 9514863
TI  - The GTS1 gene product influences the ultradian oscillation of glycolysis in cell
      suspension of the yeast Saccharomyces cerevisiae.
AB  - We tested the effect of the GTS1 gene of the yeast Saccharomyces cerevisiae on
      the cyanide-induced ultradian oscillation of the glycolytic metabolite NADH in
      cell suspension of strains with different copy numbers of the gene, that is, the
      wild-type, GTS1-disrupted and GTS1-overexpressing strains. The cells showed long
      lasting oscillations when harvested between 1 and 2 hours after the diauxic shift
      from glucose to ethanol as a growth substrate. The frequencies of oscillation did
      not vary very much among the three strains tested. However, the amplitudes and
      durations of the oscillation were changed significantly as a function of the GTS1
      gene-dosage. The effect of GTS1 on the amplitude was not caused by changing rates
      of glucose incorporation into cells as the rates were the same among the three
      strains during the macroscopic oscillation.

PMID- 9514864
TI  - Mechanism of action of the antimicrobial peptide buforin II: buforin II kills
      microorganisms by penetrating the cell membrane and inhibiting cellular
      functions.
AB  - The mechanism of action of buforin II, which is a 21-amino acid peptide with a
      potent antimicrobial activity against a broad range of microorganisms, was
      studied using fluorescein isothiocyanate (FITC)-labeled buforin II and a gel
      retardation experiment. Its mechanism of action was compared with that of the
      well-characterized magainin 2, which has a pore-forming activity on the cell
      membrane. Buforin II killed Esche-richia coli without lysing the cell membrane
      even at 5 times minimal inhibitory concentration (MIC) at which buforin II
      reduced the viable cell numbers by 6 orders of magnitude. However, magainin 2
      lysed the cell to death under the same condition. FITC-labeled buforin II was
      found to penetrate the cell membrane and accumulate inside E. coli even below its
      MIC, whereas FITC-labeled magainin 2 remained outside or on the cell wall even at
      its MIC. The gel-retardation experiment showed that buforin II bound to DNA and
      RNA of the cells over 20 times strongly than magainin 2. All these results
      indicate that buforin II inhibits the cellular functions by binding to DNA and
      RNA of cells after penetrating the cell membranes, resulting in the rapid cell
      death, which is quite different from that of magainin 2 even though they are
      structurally similar: a linear amphipathic alpha-helical peptide.

PMID- 9514865
TI  - Gene transcription and synthesis of adrenomedullin by cultured human renal cells.
AB  - Adrenomedullin (ADM) is a novel 52 amino acid peptide with a potent vasodilator
      effect. Gene expression of ADM is found in human kidney but the exact cell source
      in the kidney is uncertain. Its plasma level is raised in association with
      changes in sympathetic nervous activity and body fluid volume in hypertension and
      chronic renal failure. Herein, we examined the presence of mRNA encoding for ADM
      in cultured human glomerular cells. Adrenomedullin in cell culture supernatant
      was measured by a radio-immunoassay (with a detection level of 3.2 pmol/l).
      Adrenomedullin mRNA was found in cultured mesangial and glomerular epithelial
      cells as well as in vascular endothelial cells. Supernatant levels of ADM for
      cultured mesangial and glomerular epithelial cells were 21.2 and < 3.2 pmol/l
      respectively. Contrary to vascular smooth muscle cells, the gene expression for
      ADM in mesangial cells was up-regulated when incubated with increasing
      concentration of TNF-alpha or fetal bovine serum (FBS) but this effect was not
      observed with very high concentration. Parallel results were observed in
      adrenomedullin levels in supernatant from mesangial cell cultures. Forskolin,
      captopril, or TGF-beta had no effect on the transcription or synthesis of ADM in
      mesangial cells. The gene expression for ADM in glomerular epithelial cells was
      down-regulated when incubated with increasing concentration of TNF-alpha,
      forskolin or FBS. The ADM levels in all supernatant from resting glomerular
      epithelial cell cultures were < 3.2 pmol/l. Recent murine data show that ADM
      stimulates the release of cAMP but suppresses mitogenesis in cultured mesangial
      cells. Our results suggest ADM is synthesized by mesangial cells in an autocrine
      fashion and the peptide may potentially be involved in intra-renal blood pressure
      control.

PMID- 9514866
TI  - Negative chronotropic effect of botulinum toxin on neonatal rat cardiac myocytes.
AB  - We demonstrated that botulinum neurotoxin attenuated the spontaneous beating rate
      of cultured cardiac myocytes. Primary cultured cardiac myocytes were prepared
      from the ventricles of neonatal Wistar rats (1-3 days old). On 7 days after cell
      seeding, botulinum toxin type A incorporated into liposomes was added to the
      culture medium. At a final concentration of 5.0 micrograms/ml, botulinum toxin
      markedly attenuated the beating rate of cardiac myocytes within 2-4 hours. These
      results demonstrated the effect of SNARE-complex proteins on the spontaneous
      beating of cardiac myocytes.

PMID- 9514867
TI  - Transdifferentiation of rat hepatic stellate cells results in leptin expression.
AB  - Leptin is a peptide hormone that appears critical in regulating Fat metabolism.
      Recently, circulating leptin levels were reported higher in patients with
      alcoholic cirrhosis. In health, hepatic stellate cells store retinoids, but
      following liver injury they transdifferentiate into myofibroblast-like cells with
      loss of the retinoid stores. Leptin expression was demonstrated by detection of
      leptin mRNA by RT-PCR analysis and by immunohistochemistry viewed with confocal
      microscopy in transdifferentiated stellate cells after 14 days, or more, of
      culture. Leptin expression was not found in freshly isolated quiescent stellate
      cells. Leptin expression was not demonstrated in freshly isolated or cultured
      Kupffer cells. Treatment of activated stellate cells with either 1 microM
      retionic acid or 10 microM retinol acetate resulted in the inhibition of leptin
      mRNA expression. The observation that activated stellate cells in culture can
      express leptin has implications for understanding adipocyte biology in liver
      disease and treatment of malnutrition in cirrhotics.

PMID- 9514868
TI  - Autocrine inhibition of leptin production by tumor necrosis factor-alpha (TNF
      alpha) through TNF-alpha type-I receptor in vitro.
AB  - The aim of this study was to find factors which regulate m-leptin secretion
      during pregnancy. Mouse parametrial adipocytes from day 13 of pregnancy were
      cultured with or without mouse placental lactogen (mPL)-I, mPL-II, or mouse tumor
      necrosis factor-alpha (mTNF-alpha) and mouse-leptin (m-leptin) concentration in
      the medium was assessed by RIA. Up to four days of mPL-I or mPL-II treatment did
      not affect m-leptin secretion. However, mTNF-alpha, which is produced by
      adipocytes, significantly inhibited m-leptin secretion in a dose- and time
      dependent manner. Antibody to mTNF-alpha completely blocked the inhibitory effect
      of mTNF-alpha on m-leptin secretion. mTNF-alpha significantly inhibited the
      expression of m-leptin messenger RNA. Agonistic polyclonal antibody directed
      against the mTNF-type-I receptor (mTNF-RI) significantly inhibited m-leptin
      secretion, but the anti-mTNF-RII antibody did not change m-leptin secretion.
      Moreover, human TNF-alpha (h-TNF-alpha) also inhibited human-leptin (h-leptin)
      secretion by cultured human adipocytes collected from the subcutaneous fat of
      pregnant women. These results suggest that TNF-alpha, which is secreted by
      adipocytes, inhibits m-leptin secretion through mTNF-RI and suggest the presence
      of an autocrine or paracrine regulation of leptin secretion in human and mouse
      adipose tissue in vivo.

PMID- 9514869
TI  - Induction of Smad6 mRNA by bone morphogenetic proteins.
AB  - Members of the transforming growth factor-beta (TGF-beta) superfamily transduce
      signals via Smad proteins. Smad2 and Smad3 mediate TGF-beta signaling, whereas
      Smad1 and Smad5 transduce bone morphogenetic protein (BMP) signals. Smad4 is a
      common mediator required for both pathways. Smad6 and Smad7 are recently
      identified members in the Smad family; they inhibit the signaling activity of the
      other Smad proteins. Here we show that expression of the Smad6 mRNA is
      dramatically induced by BMP-2 or osteogenic protein-1 (OP-1)/BMP-7 in various
      cells. BMP-2 induced expression of Smad7 in one cell type, although much less
      potently than that of Smad6. Smad6 message was induced by TGF-beta 1 in TGF-beta
      1-responsive Mv1Lu cells, but the induction was transient in contrast to the
      induction by BMPs. These results indicate that Smad6 may form a feedback loop to
      regulate the signaling activity of BMPs.

PMID- 9514870
TI  - Difference in chromatin packaging between active and inactive X chromosomes by
      fractionation and allele-specific detection.
AB  - Using a novel method consisting of chromatin fractionation and allele-specific
      detection, chromatin packaging is compared between active X (Xa) and inactive X
      (Xi) chromosomes for five tumor cell clones that were derived from inter
      subspecific F1 female mice. Separation of heterochromatic (H) and euchromatic (E)
      fractions is monitored by hybridization with subtelomeric satellite DNA and
      ribosomal RNA gene and by PCR amplification of p53 gene/pseudogene with one
      primer set. The H fraction was enriched with satellite and p53 pseudogene
      probably existing in heterochromatic regions while the E fraction showed inverse,
      suggesting fair separation. Analysis with seven marker and three gene loci
      revealed concentration of alleles on Xi in the H fraction and those on Xa in the
      E fraction, though the concentration levels varied. This implies that the
      packaging level of Xi is higher than that of active or inactive euchromatin on
      Xa. Intriguingly, one cell line showed biallelic expression and chromatin
      relaxation of the Pgk-1 locus, suggesting that the relaxation occur regionally on
      X chromosome.

PMID- 9514871
TI  - Complex formation of NS5B with NS3 and NS4A proteins of hepatitis C virus.
AB  - At present, the mechanism of replication of the HCV genome remains unclear.
      Recently, NS5B and NS3 of HCV have been shown to exhibit RNA-dependent RNA
      polymerase and helicase activities, respectively, both of which are indispensable
      for virus RNA replication. In this study, we examined the complex formation of
      NS5B with NS3 and NS4A, a cofactor for NS3. We show here that NS5B forms a
      complex with NS3 through an amino-terminal portion of NS3. The NS3-NS5B complex
      formation took place both in the presence and absence of NS4A. We also
      demonstrate that NS5B form a complex with NS4A in the absence of NS3. These
      results suggest that NS3, NS4A and NS5B interact with each other to form a
      complex that functions as part of the replication machinery of HCV.

PMID- 9514872
TI  - Increased pentosidine, an advanced glycation end product, in plasma and synovial
      fluid from patients with rheumatoid arthritis and its relation with inflammatory
      markers.
AB  - Pentosidine is an advanced glycation end product (AGE) formed by combined
      processes of glycation and oxidation (glycoxidation) between carbohydrate-derived
      carbonyl group and protein amino group. Recent studies demonstrated the increased
      pentosidine levels not only in diabetic patients with hyperglycemia but also in
      normoglycemic uremic patients due to increased oxidative stress. Rheumatoid
      arthritis (RA) is a state of increased oxidative stress associated with chronic
      inflammation. This suggested an enhanced glycoxidation reaction and increased AGE
      levels in RA patients. In the present study, we therefore determined, by high
      performance liquid chromatographic (HPLC) assay, the concentrations of
      pentosidine in plasma and synovial fluid from 22 patients with rheumatoid
      arthritis (RA) and compared their levels with those in 17 patients with
      osteoarthritis (OA), 26 diabetic patients, and 25 normal subjects. The levels of
      inflammatory markers and markers of tissue destruction, metalloproteinases (MMPs)
      and tissue inhibitors of metalloproteinases (TIMPs), were also measured in the
      same samples. Pentosidine levels in plasma and synovial fluid from RA patients
      were significantly higher than those in OA patients, diabetic patients, and
      normal subjects. There was a significant correlation between the pentosidine
      levels in plasma and those in synovial fluid. Among markers of inflammation and
      matrix destruction, pentosidine levels in plasma from RA patients were correlated
      with the levels of C-reactive protein (CRP), erythrocyte sedimentation rate,
      white blood cell count, and platelet count. Multiple stepwise regression analysis
      reveals an independent influence of CRP on plasma pentosidine levels. In
      conclusion, pentosidine levels are significantly higher in plasma and synovial
      fluid from RA patients and may be useful as a biomarker of chronic inflammation
      in RA patients.

PMID- 9514874
TI  - Differential response of the human cyclin B1 promoter to inhibitors of the cell
      cycle in NIH3T3 cells.
AB  - In this study, NIH3T3 cells stably transfected with a cyclin B1-luciferase
      reporter vector were utilized to investigate if cyclin B1 promoter activity is
      linked to either DNA replication or the activities of various cyclin-cyclin
      dependent kinases (cdks). Synchronized cells treated at the time of serum re
      stimulation with 2 micrograms/ml of the DNA synthesis inhibitor, aphidicolin, did
      not display an increase in luciferase activity in comparison to control cells.
      When treated with aphidicolin during S phase, luciferase activity decreased. In
      contrast, luciferase activity increased in cells treated at the time of serum re
      stimulation with 200 microM olomoucine, a cyclin-cdk inhibitor. These results
      indicate that (1) cyclin B1 promoter activity in NIH3T3 cells is linked to a DNA
      replication checkpoint control mechanism; (2) the cyclin B1 gene can be activated
      in the absence of functional cyclin E-cdk2, cyclin A-cdk2, or cyclin B-cdk2; and
      (3) cyclin B1 gene activation can occur in G1 arrested cells under conditions in
      which the arrest is not directly linked to inhibition of DNA synthesis.

PMID- 9514873
TI  - Regulation of CCAAT/enhancer binding protein alpha (C/EBP alpha) gene expression
      by thiazolidinediones in 3T3-L1 adipocytes.
AB  - Thiazolidinediones are a class of antidiabetic drugs that induce preadipocyte
      differentiation by binding and activating peroxisome proliferator-activated
      receptor gamma 2. Although thiazolidinediones are commonly thought of as insulin
      sensitizing agents, these drugs have opposing and antagonistic effects to that of
      insulin on CCAAT/enhancer binding protein alpha (C/EBP alpha) gene expression in
      fully differentiated 3T3-L1 adipocytes. Thiazolidinediones induce expression of
      C/EBP alpha mRNA and protein, while insulin stimulates a rapid decline in C/EBP
      alpha mRNA and protein. When added in combination, thiazolidinediones block the
      suppression of C/EBP alpha mRNA by insulin; however, thiazolidinediones do not
      block the insulin-induced decline in GLUT4 mRNA, indicating that repression of
      C/EBP alpha mRNA is not required for insulin to suppress expression of a C/EBP
      alpha-responsive gene such as GLUT4. Instead, insulin may regulate GLUT4 mRNA by
      inactivating C/EBP alpha through dephosphorylation as well as by inducing the
      expression of the dominant-negative form of C/EBP beta (liver inhibitory
      protein), since both of these processes occur in the presence of
      thiazolidinediones.

PMID- 9514875
TI  - Increased expression of the secretory Na+-K+-2Cl- cotransporter with
      differentiation of a human intestinal cell line.
AB  - We studied the expression of the secretory Na(+)-K(+)- 2Cl- cotransporter during
      epithelial differentiation using the clonal human adenocarcinoma cell line HT29
      18. Differentiation of HT29-18 cells was accompanied by up to 7-fold increases in
      cotransporter protein levels, approximately 3-fold increases in cotransporter
      mRNA levels, and approximately 2.5-fold increases in cotransporter functional
      expression. No apparent change in cotransporter mRNA stability was observed with
      differentiation, suggesting that these effects may be due to differences in mRNA
      transcription rate. Confocal immunofluorescence microscopy showed that
      undifferentiated cells grew in multilayers and exhibited a diffuse, apparently
      unlocalized membrane labeling by anti-Na(+)-K(+)-2Cl- cotransporter antibody. In
      contrast, differentiated cells grew in monolayers with strong cotransporter
      labeling localized to the basal and lateral membranes. Taken together with
      previous studies demonstrating that expression of the cystic fibrosis
      transmembrane regulator is also increased following HT29-18 cell differentiation,
      our results suggest that these cells provide a promising model for studying
      epithelial differentiation to a Cl- secretory phenotype.

PMID- 9514876
TI  - 4-Bromocrotonic acid enhances basal but inhibits insulin-stimulated glucose
      transport in 3T3-L1 adipocytes.
AB  - Inhibitors of fatty acid oxidation, 2-bromopalmitic acid (Br-C16) and 4
      bromocrotonic acid (Br-C4) were examined for their effect on glucose transport in
      3T3-L1 adipocytes. Whereas Br-C16 was without effect, Br-C4 augmented basal but
      inhibited insulin-stimulated 2-deoxyglucose uptake in a dose- and time-dependent
      manner. Immunoblot analysis indicated that following Br-C4 pretreatment, the
      content of GLUT1 in plasma membranes was increased whereas insulin-induced
      translocation of GLUT4 was greatly eliminated. The total cellular amount of GLUT1
      or GLUT4, on the other hand, was not altered. Thus these results seem to suggest
      that Br-C4 has opposite effect on basal and insulin-stimulated glucose transport
      by a mechanism other than its inhibition of fatty acid oxidation. The
      translocation processes for both GLUT1 and GLUT4 transporters appears to be
      altered.

PMID- 9514877
TI  - Tyrosine kinases of the Src family participate in signaling to MAP kinase from
      both Gq and Gi-coupled receptors.
AB  - Src-related kinases have been recently implicated in signaling from Gi-coupled
      receptors to MAP kinase. Whether Src-like kinases participate in MAP kinase
      activation by the large family of receptors coupled to G proteins of the Gq
      family is still unclear. Here, we show that a specific inhibitor for Src-like
      kinases, 4-amino-5-(4-methylphenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine (PP1),
      and dominant negative mutants of Src suppress MAP kinase activation in COS-7
      cells when elicited by either m1 and m2 muscarinic receptors, which are typical
      Gq and Gi-coupled receptors, respectively. Furthermore, activation of MAP kinase
      by overexpression of beta gamma subunits, but not by stimulation with phorbol
      esters was also inhibited by the dominant-negative Src. In contrast, a dominant
      negative Pyk2 had only mild effects on m1 and m2 mediated-MAP kinase activation.
      We concluded that Src like kinase(s), acting downstream from beta gamma dimers,
      play an important role relaying signals from both Gq and Gi-coupled receptors to
      MAP kinase.

PMID- 9514878
TI  - Discovery of nonsteroidal androgens.
AB  - Nonsteroidal androgens have not been reported. During studies to identify
      affinity ligands for the androgen receptor in our laboratory, we synthesized
      several electrophilic nonsteroidal ligands for the androgen receptor and examined
      their receptor binding affinity and ability to stimulate receptor-mediated
      transcriptional activation. We found that three of these ligands (1) bound the
      androgen receptor with affinity similar to that of dihydrotestosterone (the
      endogenous ligand) and (2) mimicked the effects of dihydrotestosterone on
      receptor-mediated transcriptional activation (i.e., they were receptor agonists).
      These studies demonstrate that nonsteroidal ligands can be structurally modified
      to produce agonist activity. These ligands thus represent the first members of a
      novel class of androgens with potential therapeutic applications in male
      fertility and hormone replacement therapy.

PMID- 9514879
TI  - Ionizing radiation activates c-Jun NH2-terminal kinase (JNK/SAPK) via a PKC
      dependent pathway in human thyroid cells.
AB  - Thyroid gland is known to be higher sensitive to carcinogenic effects of external
      ionizing radiation (IR) than other tissues. To clarify the cell-specific response
      following irradiation, activations of c-Jun NH2-terminal kinases (JNKs), which is
      one of mitogen-activated protein kinases (MAPKs) family members, and
      extracellular signal-regulated kinase (ERK) were examined in primary cultured
      human thyroid cells in comparison with human diploid fibroblast cells, WI-38.
      Although UV exposure strikingly induced JNK activity in both cells, the dose
      response increase following IR exposure was observed in thyroid cells with the
      maximal JNK activity (3.5 fold induction) obtained at 10 Gy exposure, but no
      increase in WI-38 cells. The JNK activity was reached a maximum of 2.2 fold
      induction at 30 min after 5 Gy exposure and then sustained for at least 12 hr. On
      the other hand, ERK activity was not stimulated in thyroid cells following
      irradiation. The effects of 12-O-tetradecanoylphorbol beta-acetate (TPA) mimicked
      those of radiation on JNK cascade and 1-(5-isoquinolinesulphonyl)-2,5
      dimethylpiperazine 2HCl (H7) and pretreatment with TPA blocked JNK activation
      following irradiation. Our results demonstrate that IR stimulates JNK activity in
      cultured human thyroid cells but not in fibroblasts indicating distinct
      activation and regulation mechanisms of JNK cascade. The JNK activation following
      IR exposure is mediated at least partially through a PKC-dependent pathway.

PMID- 9514880
TI  - Gene expression of growth and differentiation factors-5, -6, and -7 in developing
      bovine tooth at the root forming stage.
AB  - Growth and differentiation factors (GDF)-5, -6, and -7 are members of the bone
      morphogenetic protein (BMP) family. Previous studies suggest their importance in
      bone development and in tendon/ligament morphogenesis. The cells of the dental
      attachment apparatus, cementum, periodontal ligament, and alveolar bone proper
      are derived from the dental follicle proper. In this study, we investigated the
      expression of GDF-5, -6, and -7 genes in tissues of the bovine incisor tooth germ
      at the root forming stage. The results demonstrate distinct expression of GDFs in
      both the dental follicle and the odontoblast layer. While GDF-5 and -6 mRNAs were
      expressed in both the dental follicle and the odontoblast layer, GDF-7 mRNA
      expression was detected only in the dental follicle. These results indicate that
      GDFs, expressed in the bovine tooth germ including the dental follicle, may be
      potent regulatory molecules in the development of the dental attachment
      apparatus.

PMID- 9514881
TI  - Cloning and developmental expression of a nuclear ubiquitin-conjugating enzyme
      (DmUbc9) that interacts with small heat shock proteins in Drosophila
      melanogaster.
AB  - In a two hybrid screen designed to identify proteins that interact with small
      heat shock proteins (sHsps), a Drosophila melanogaster homologue of yeast and
      human ubc9 (Dmubc9) was found to interact with Drosophila Hsp23. Further, two
      hybrid system analysis reveals DmUbc9 interaction with Drosophila and mammalian
      Hsp27. In situ hybridization localizes Dmubc9 as a doublet at locus 21D on
      chromosome 2L, and genomic cloning of the gene reveals a single open reading
      frame without introns. The predicted Dmubc9 protein sequence shares a very high
      level of homology with mouse (85.4%) and human (> or = 82.9%) Ubc9. Genetic
      complementation analysis show that Dmubc9 functionally rescues a temperature
      sensitive S. cerevisiae ubc9ts mutant. Co-immunoprecipitation with antibody
      raised against DmUbc9 confirms the interaction with Drosophila Hsp23 and Hsp26
      and preferentially with Hsp27. The DmUbc9 protein, which localizes primarily to
      the nucleus in Drosophila S2 cells, is found at high levels in embryos but is
      also present at lower levels throughout development. The significance of the sHsp
      Ubc9 interaction is discussed.

PMID- 9514882
TI  - A role for protein kinase C alpha in stimulation of prostaglandin G/H synthase-2
      transcription by 14,15-epoxyeicosatrienoic acid.
AB  - Arachidonic acid, but not eicosapentaenoic acid, increased prostaglandin G/H
      endoperoxide synthase-2 transcription in cultured intestinal epithelial cells.
      This stimulatory effect on PGHS-2 synthesis was prevented by an AA utilization
      inhibitor, eicosatetraynoic acid. Specific inhibitors of the cyclooxygenase or
      the lipoxygenase pathways of AA metabolism did not prevent AA-mediated induction
      of PGHS-2 synthesis; however, the involvement of cytochrome P450 monoxygenases
      (CYP450) was indicated as several CYP450 blockers, ketoconazole, miconazole, and
      metyrapone, inhibited the induction of PGHS-2 mRNA synthesis by AA. This blockade
      by CYP450 inhibitors could be overcome by the addition of the AA epoxygenase
      metabolite 14,15-epoxyeicosatrienoic acid (14,15-EET); other EET regio-isomers
      were unable to elevate PGHS-2 mRNA level. Blockade of protein kinase C with a
      specific inhibitor, bisindolyl maleimide-1, or translational inhibition of
      protein kinase C alpha by antisense oligonucleotides reduced PGHS-2
      transcription, suggesting the involvement of protein kinase C alpha in the signal
      transduction pathway.

PMID- 9514883
TI  - Transcriptional activation of the mouse HSP47 gene in mouse osteoblast MC3T3-E1
      cells by TGF-beta 1.
AB  - HSP47 is a 47-kDa collagen-binding heat shock protein, the expression of which is
      always correlated with that of collagens in various cell lines. We examined the
      effects of TGF-beta 1, which is reported to induce the collagen genes, on the
      expression of HSP47 in mouse osteoblast MC3T3-E1 cells. Treatment of the cells
      with 5 ng/ml TGF-beta 1 for 24 h increased the level of HSP47 mRNA three-fold.
      Dose-dependent induction by TGF-beta 1 was observed for both HSP47 mRNA and
      collagen alpha 1 (I) mRNA, and actinomycin D inhibited this increase of HSP47
      mRNA. To elucidate the TGF-beta 1 responsive element(s) in the mouse HSP47 gene,
      we generated a series of 5'-deletion promoters fused to luciferase reporter
      constructs. Transient transfection assays showed that TGF-beta 1 induced 4-6 fold
      the promoter activity of a region approximately -5.5 kbp upstream of the HSP47
      gene. Two upstream regions, -3.9 to -2.7 kbp and -280 to -50 bp were shown to be
      involved in the activation in response to TGF-beta 1 treatment.

PMID- 9514884
TI  - Detection of an interleukin-1 intracellular receptor antagonist mRNA variant.
AB  - At least two versions of interleukin-1 receptor antagonist generated by
      alternative splicing are found intracellularly, but their functions remain poorly
      characterized. During studies aimed at characterizing the expression of these
      transcripts in human articular cartilage, we detected a variant cDNA species that
      contained an additional 171 nucleotides within the type I interleukin-1
      intracellular receptor antagonist cDNA which interrupted the coding region. This
      mRNA variant was also found to be expressed in keratinocytes. Translation likely
      initiates at an alternate methionine codon than that utilized for the previously
      reported interleukin-1 intracellular receptor antagonist isoforms, suggesting
      that this mRNA variant encodes a novel polypeptide that may play a role in
      interleukin-1 signaling.

PMID- 9514885
TI  - Alteration of the fatty acid substrate specificity of lysophosphatidate
      acyltransferase by site-directed mutagenesis.
AB  - The JC201 strain of Eschericia coli contains a temperature-sensitive lesion in
      lysophosphatidate acyltransferase (LPAT) activity. The LPAT gene from JC201 was
      isolated by PCR and a single mutant nucleotide, adenine-440, was identified by
      DNA sequence analysis. Site-directed mutagenesis converted the mutant adenine-440
      back to the native guanine-440 nucleotide. The restored LPAT gene rescued JC201
      cells at the non-permissive temperature. The fatty acid substrate specificity of
      LPAT from Eschericia coli was altered by site-directed mutagenesis of a single
      amino acid in the restored LPAT gene. Threonine-122 of LPAT was changed to
      alanine or leucine. A change from threonine-122 to alanine increased the
      substrate specificity in vitro for oleoyl-CoA and linoleoyl-CoA; whereas a change
      to leucine increased the substrate specificity for lignoceroyl-CoA.

PMID- 9514886
TI  - Induction of UCP2 gene expression by LPS: a potential mechanism for increased
      thermogenesis during infection.
AB  - UCP2 has been proposed to regulate thermogenesis and energy expenditure. To
      identify potential mechanisms underlying the increased energy expenditure and
      heat production during infection, we investigated whether LPS and cytokines might
      increase UCP2 mRNA levels in mice. LPS (100 micrograms, i.p.) increased the
      expression of UCP2 mRNA in liver (28-fold) and muscle and white adipose tissue (5
      fold). In liver, both IL-1 beta (1 microgram, i.p.) and TNF (5 micrograms, i.p.)
      increased UCP2 mRNA levels, 4- and 3-fold respectively, whereas in muscle and fat
      tissue, an increase was detectable after TNF, but not IL-1 beta. Indomethacin (10
      mg/kg, i.p.) administered immediately before LPS markedly reduced (70%) the
      ability of LPS to increase UCP2 mRNA in liver, but not in muscle or adipose
      tissue. These results suggest a role for UCP2 in the heat production and
      increased energy expenditure that occurs during infection.

PMID- 9514887
TI  - Interaction of phospholipase C gamma 1 via its COOH-terminal SRC homology 2
      domain with synaptojanin.
AB  - The role of the phospholipase C gamma 1 (PLC gamma 1) in signal transduction was
      investigated by characterizing its interactions with proteins that may represent
      components of a novel signalling pathway. A 145-kDa protein that binds SH2 domain
      of PLC gamma 1 was purified from rat brain. The sequence of peptide derived from
      the purified binding protein now identify it as synaptojanin, a nerve terminal
      protein that has been implicated in the endocytosis of fused synaptic vesicles
      and shown to be a member of the inositol polyphosphate 5-phosphatase family. We
      demonstrate here stable association of PLC gamma 1 with synaptojanin, a protein
      that not only binds carboxyl terminal SH2 domain of PLC gamma 1, but also
      inhibits PLC gamma 1 activity.

PMID- 9514888
TI  - Ceramide selectively inhibits calcium-mediated potentiation of beta-adrenergic
      stimulated cyclic nucleotide accumulation in rat pinealocytes.
AB  - Interaction between sphingomyelin metabolism and cyclic nucleotide synthesis in
      rat pinealocytes was investigated by determining the effect of ceramide on
      adrenergic-stimulated cAMP and cGMP accumulation. Although C2-, C6-, and C8
      ceramide had no effect on basal, isoproterenol-, or norepinephrine-stimulated
      cAMP and cGMP accumulation, they inhibited the potentiation caused by
      depolarising concentrations of K+ or BayK 8644. Similar inhibition was observed
      when ceramide metabolism was inhibited by a glucosylceramide synthase inhibitor.
      In contrast, the potentiation of cAMP and cGMP accumulation caused by other
      intracellular Ca(2+)-elevating agents such as ionomycin or thapsigargin or by an
      activator of protein kinase C was not affected by ceramide. Taken together, our
      results suggest that ceramide selectively inhibits cyclic nucleotide synthesis
      when the nucleotide synthesis is potentiated by an increase in intracellular Ca2+
      through L-type Ca2+ channels and that the sphingomyelin cycle probably plays an
      important role in the regulation of these channels.

PMID- 9514889
TI  - Transcriptional role of the nuclear factor kappa B site in the induction by
      lipopolysaccharide and suppression by dexamethasone of cyclooxygenase-2 in U937
      cells.
AB  - Cyclooxygenase-2 (COX-2), an inducible isozyme of cyclooxygenase, is selectively
      expressed in response to lipopolysaccharide (LPS) and its expression is
      suppressed by the glucocorticoid dexamethasone (DEX) in the monocytic
      differentiated U937 cells. However, COX-2 mRNA was not detected nor induced by
      LPS before the cells differentiated. To study the transcriptional role of the NF
      kappa B site (nucleotides -223 to -214) in the COX-2 gene, the luciferase
      reporter vector driven by the COX-2 promoter region (nucleotides -327 to +59)
      mutated at both the cAMP response element and the NF-IL6 site was stably
      transfected into U937 cells. The substantial luciferase activity observed in the
      undifferentiated cells was not induced by LPS. However, after the cells had
      differentiated, luciferase activity was induced by LPS and its induction was
      suppressed by DEX. Moreover, a protein tyrosine kinase inhibitor herbimycin A
      suppressed both the expression of COX-2 mRNA and the luciferase activity induced
      by LPS. These results suggest that the NF-kappa B site is involved in both the
      LPS-induced expression of the COX-2 gene and its suppression by DEX and
      herbimycin A in a differentiation-dependent manner.

PMID- 9514890
TI  - Interferon-gamma inhibits the growth of human bronchial epithelial cells
      independently of transforming growth factor-beta-1 and nitric oxide (NO).
AB  - It has been emphasized that epithelial injury is closely correlated with airway
      hyperresponsiveness, which is one of the important pathophysiological
      characteristics of bronchial asthma. Growth of epithelial cells is important in
      the mucosal repair processes and is believed to be regulated by growth factors
      produced by inflammatory and immune effector cells as well as epithelial cells
      themselves. We studied the role of T cell-derived lymphokines IFN gamma and IL-4
      on the proliferation of human bronchial epithelial cell line BEAS-2B. IFN gamma,
      but not IL-4, showed a dose-dependent growth inhibitory activity in vitro. Its
      activity was via its specific receptors on the cells, was augmented by TNF alpha,
      and was independent of the activity of endogenous TGF beta and nitric oxide.
      These results suggested that Th-1 T cells-derived lymphokine IFN gamma might be
      involved in the repair processes after mucosal injury found in bronchial asthma.

PMID- 9514891
TI  - UVB-induced reduction in biomass and overall productivity of cyanobacteria.
AB  - Effect of middle wave ultraviolet radiation (UVB) was studied in three different
      species of cyanobacteria (Nostoc, Anabaena and Scytonema) by estimating their
      growth pattern, biomass yield, chlorophyll content, total starch and protein
      content. The results show that exposure of the cyanobacteria with UVB dose
      corresponding to an increase or decrease of 20% in its environmental flux will
      have drastic effects on biomass production, photosynthetic rate and nitrogen
      fixation. Cyanobacteria are primary sources of marine food web and an important
      biofertilizer; therefore, their protection from increasing threat of
      stratospheric ozone depletion will be necessary to maintain the ecological
      balance.

PMID- 9514892
TI  - The inhibitory specificity of human proteinase inhibitor 8 is expanded through
      the use of multiple reactive site residues.
AB  - Serine proteinase inhibitors function as regulators of serine proteinase activity
      in a variety of physiological processes. Proteinase inhibitor 8 (PI8) is a 45 kDa
      member of the ovalbumin family of serpins that is an inhibitor of trypsin-like
      proteinases through the use of Arg339 as the inhibitory P1 amino acid residue in
      its reactive site loop. In this study, we have described the inhibitory mechanism
      of recombinant human PI8 towards chymotrypsin. PI8 formed an SDS-stable complex
      with and inhibited the amidolytic activity of chymotrypsin via a two-step
      mechanism with an overall equilibrium inhibition constant of 1.7 nM and an
      overall second-order association rate constant of 1.0 x 10(4) M-1s-1, utilizing
      Ser341 as the P1 residue. The use of separate reactive site loop residues by PI8
      to inhibit distinctly different classes of proteinases not only supports the
      hypothesis of the existence of the serpin reactive site as a highly mobile and
      flexible loop, but also suggests an evolved function in which separate amino acid
      residues can be used to broaden the inhibitory specificity of PI8.

PMID- 9514893
TI  - Characterization, cloning, and expression of porcine alpha B crystallin.
AB  - alpha-Crystallin is a major lens protein present in the lenses of all vertebrate
      species. Recent studies have revealed that bovine alpha-crystallins possess
      genuine chaperone activity similar to small heat-shock proteins. In order to
      compare this chaperone-like structural protein from the eye lenses of different
      mammalian species, we have cloned and expressed one of the main alpha-crystallin
      subunits, i.e., alpha B crystallin, from the porcine lenses in order to
      facilitate the structure-function evaluation and comparison of this chaperonin
      protein. cDNA encoding alpha B subunit chain was obtained using a new "Marathon
      cDNA amplification" protocol of Polymerase Chain Reaction (PCR). PCR-amplified
      product corresponding to alpha B subunit was then ligated into pGEM-T plasmid and
      prepared for nucleotide sequencing by the dideoxy-nucleotide chain-termination
      method. Sequencing several positive clones containing DNA inserts coding for
      alpha B-crystallin subunit constructed only one complete full-length reading
      frame of 525 base pairs similar to human and bovine alpha B subunits, covering a
      deduced protein sequence of 175 amino acids including the universal translation
      initiating methionine. The porcine alpha B crystallin shows only 3 and 7 residues
      difference to bovine and human alpha B crystallins respectively, revealing the
      close relatedness among mammalian eye lens proteins. The sequence differences
      between porcine and sub-mammalian species such as chicken and bullfrog are much
      greater, especially at the N- and C-terminal regions of these alpha B
      crystallins. Expression of alpha B subunit chain in E. coli vector generated a
      polypeptide which can cross-react with the antiserum against the native and
      purified alpha B subunit from the native porcine lenses albeit with a much lower
      activity.

PMID- 9514894
TI  - The reaction of S-nitrosoglutathione with superoxide.
AB  - The nitric oxide (NO)-dependent S-nitrosation of thiols to generate S
      nitrosothiols has been proposed as an important pathway for the metabolism of NO
      in vivo. Although it has been suggested that these S-nitrosated compounds are
      resistant to decomposition by reactive oxygen metabolites (ROMs), very little
      information is available regarding the interaction between S-nitrosothiols and
      ROMs. We found that S-nitrosoglutathione (GSNO) rapidly reacted with O2- to
      generate glutathione disulfide and equimolar quantities of nitrite and nitrate.
      The reaction was second order with respect of GSNO and first order with respect
      of O2- with a rate equation of -d[GSNO]/dt = 2k3[GSNO]2[O2-], where k3 = 3 - 6 x
      10(8) M-2s-1. In addition, the reaction of GSNO with O2- generated a strong
      oxidant as an intermediate capable of oxidizing dihydrorhodamine in the absence
      of the apparent generation of NO. We conclude that O2- may act as a physiological
      modulator of S-nitrosation reactions by directly promoting the decomposition of S
      nitrosothiols.

PMID- 9514895
TI  - Oxidation of phenanthrene by a fungal laccase in the presence of 1
      hydroxybenzotriazole and unsaturated lipids.
AB  - Phenanthrene, a polycyclic aromatic hydrocarbon, was efficiently oxidized by
      laccase in the presence of both 1-hydroxybenzotriazole and unsaturated lipids.
      73% of initially added phenanthrene was degraded within 182 hours to give
      phenanthrene-9,10-quinone and 2,2'-diphenic acid as the major products. The
      system was also able to peroxidize linoleic acid to its corresponding
      hydroperoxides suggesting the involvement of lipid peroxidation in laccase
      catalyzed phenanthrene oxidation. Lipid peroxidation by laccase required 1
      hydroxybenzotriazole and did not depend on Mn2+ and H2O2 suggesting that the
      chemical reactions involved differ from those previously reported for manganese
      peroxidase.

PMID- 9514896
TI  - Enhanced activation of the mineralocorticoid receptor in genetically hypertensive
      rats.
AB  - The relative abundance and availability of the mineralocorticoid receptor (MCR)
      appeared to be similar in the heart, kidney and ocular tissues of the genetically
      hypertensive SHR and normotensive WKY rats by a number of criteria including
      Western blotting, immunoprecipitation, dot blot analysis, and
      immunohistochemistry. On the other hand, the activation of the MCR, as judged by
      binding to DNA cellulose, was significantly enhanced in the hearts and kidneys of
      14 week-old, hypertensive, SHR rats compared to the normotensive WKY animals. The
      activation of the renal MCR was elevated in the SHR strain even at the age of six
      weeks when the tail arterial pressure was statistically identical to that of the
      WKY strain. Thus, precocious receptor activation may represent a primary lesion
      leading to hypertension in the SHR strain, thereby providing a new model to
      elucidate the hypertensive state.

PMID- 9514897
TI  - A novel Dictyostelium discoideum gene required for cAMP-dependent cell
      aggregation.
AB  - Using a method of random insertional mutagenesis called REMI (restriction enzyme
      mediated integration), we isolated two mutant strains of Dictyostelium discoideum
      with a defect in cAMP-dependent cell aggregation. On bacterial lawns, both of the
      cells formed large and smooth plaques. When starved in a non-nutrient medium,
      they became elongated and extended pseudopods very frequently like starved wild
      type cells. However, they never formed streams toward an aggregation center.
      Genomic DNA fragments flanking the sites of insertion of the REMI tag were
      rescued from the mutant cells. The fragments contained one common open reading
      frame encoding a protein of 1148 amino acid residues. The protein's sequence is
      homologous to those of two hypothetical proteins of S. cerevisiae and S. pombe.

PMID- 9514898
TI  - Contribution of CR3 to nitric oxide production from macrophages stimulated with
      high-dose of LPS.
AB  - The contribution of the complement receptor type 3 (CR3) to nitric oxide (NO)
      production from macrophages stimulated by LPS was investigated. When
      thioglycollate-elicited mouse peritoneal macrophages were stimulated with a high
      dose of LPS (10 micrograms/ml) in both the presence and absence of fetal calf
      serum, a source of LPS binding protein (LBP) necessary for the binding of LPS to
      CD14, NO production was observed. These findings suggest that CD14-dependent and
      CD14-independent signaling pathways for NO production are present in macrophages.
      Because binding and phagocytosis of bacteria by macrophages through the CR3 has
      been previously reported, we investigated whether the CR3 acts in CD14
      independent signaling pathway for NO production. By flow cytometric analysis, the
      binding of FITC-labeled anti-CR3 monoclonal antibody (anti-CR3 mAb) to
      macrophages was inhibited by LPS. Anti-CR3 mAb induced iNOS protein and produced
      NO in a dose dependent manner. Further, NO production induced by anti-CR3 mAb was
      also inhibited by zymocel, beta-glucan with a high affinity to CR3. These results
      suggest that the CR3 molecule acts in a CD14-independent signaling pathway, and
      contributes to NO production by macrophages stimulated with high doses of LPS.

PMID- 9514899
TI  - Central delivery of human tissue kallikrein gene reduces blood pressure in
      hypertensive rats.
AB  - The human tissue kallikrein gene, in the form of naked DNA (CMV-cHK) or an
      adenoviral vector (Ad.CMV-cHK), was directly delivered by intracerebroventricular
      injection into spontaneously hypertensive rats. Control rats received the same
      amount of vector DNA (pcDNA3) or adenoviral vector (Ad.CMV-LacZ) carrying the
      lacZ gene. A single injection of the human tissue kallikrein gene caused a rapid
      and prolonged blood pressure-lowering effect that began 1 day post injection and
      the effect lasted for more than 7 days. The expression of human tissue kallikrein
      and its mRNA was identified in the cortex, cerebellum, brain stem, hippocampus
      and hypothalamus. Cellular localization of beta-galactosidase was detected by X
      gal staining in the thalamus, hypothalamus and third ventricle in rats injected
      with Ad.CMV-LacZ. This suggests that the tissue kallikrein-kinin system may
      function in the central control of blood pressure homeostasis.

PMID- 9514900
TI  - Fluorescent probing with felodipine of the dihydropyridine receptor and its
      interaction with the ryanodine receptor calcium release channel.
AB  - The intensity of the fluorescence emission of the fluorescent 1,4-dihydropyridine
      (DHP) derivative felodipine increased upon binding to both isolated cardiac
      sarcolemma (SLM) and skeletal muscle sarcoplasmic reticulum (SR) preparations,
      the latter containing SR-transversal tubule junctional diads and triads. The
      fluorescence enhancement was due to the binding of felodipine to high-affinity
      (Kd's of 0.35 and 1.25 nM in cardiac SLM and skeletal SR, respectively) 1,4
      dihydropyridine sites of the dihydropyridine receptor (DHPR), as evidenced in
      competition experiments with the DHP analog isradipine. In both cardiac SLM and
      SR, the felodipine fluorescence was sensitive to conformational changes of the
      DHPR, as diltiazem that binds to DHPR at a separate site altered the values of
      both the Kd and the Hill coefficient characteristic for felodipine binding. In
      skeletal muscle membranes containing intact TT-SR junctions, ryanodine, a
      specific ligand of the ryanodine receptor calcium release channel (RyRC), also
      induced changes in felodipine fluorescence, which was eliminated by detergent and
      high-salt treatment to solubilize the RyRC. These results suggest that i)
      felodipine fluorescence is useful to probe conformational changes of the DHPR and
      ii) coupled conformational changes between the DHPR and the RyRC in skeletal
      muscle indeed occur and could be monitored by measuring felodipine fluorescence.

PMID- 9514901
TI  - A novel calcium-independent enzyme capable of incorporating putrescine into
      proteins.
AB  - A Ca(++)-independent enzyme capable of incorporating [3H]-putrescine into
      proteins was detected in the rat intestine mucosa. The Ca(++)-independent
      incorporation of [3H]-putrescine into proteins was temperature-, pH-, time-, and
      dose-dependent. However, this enzyme was absent in the gastric mucosa. Similar to
      testicular Ca(++)-dependent transglutaminase, the optimal pH of intestinal Ca(++)
      independent enzyme was 9.0. At 10(-5) M or less putrescine concentrations, the
      Ca(++)-independent enzyme in an intestinal cytosol preparation showed a greater
      activity than did the Ca(++)-dependent transglutaminase. However, at higher
      putrescine concentrations, the latter showed a greater activity than did the
      former. Both the intestinal Ca(++)-dependent and independent enzymes were
      inhibited by cystamine, thermal labile at 50 degrees C and precipitated by 30 to
      50% saturation of ammonium sulfate. The fact that these two enzymes shared many
      similar characteristics, with the exceptions of Ca(++)-requirement, suggests that
      they may have similar active site and intrinsic molecular function(s).

PMID- 9514902
TI  - Effects of the M1 agonist xanomeline on processing of human beta-amyloid
      precursor protein (FAD, Swedish mutant) transfected into Chinese hamster ovary-m1
      cells.
AB  - Complementary DNA (cDNA) encoding human beta-amyloid precursor protein familial
      Alzheimer's disease (FAD) Swedish mutant (beta APPSM) form was cloned into a
      mammalian expression vector (PK255) containing the CMV promoter. The vector was
      transfected into Chinese hamster ovary cells containing human muscarinic m1
      receptors (CHO-m1), and clonal cells stably expressing beta APPSM were isolated.
      The effects of m1-receptor activation by the selective m1 agonist xanomeline and
      the non-selective muscarinic agonist carbachol on processing of beta APPSM to
      release soluble APP (APPs) and beta-amyloid peptide (A beta) were compared.
      Xanomeline stimulated APP release with a potency 1000-fold greater than that
      observed for carbachol. Concentrations of carbachol and xanomeline producing
      maximal effects on APPs release reduced the secretion of A beta by 28 and 46%,
      respectively. These results extend previous studies with xanomeline and suggest
      that cholinergic replacement therapy for Alzheimer's disease may reduce amyloid
      deposition.

PMID- 9514903
TI  - Interleukin-18 activates the IRAK-TRAF6 pathway in mouse EL-4 cells.
AB  - The pleiotropic biological activities of interleukin-18 (IL-18) are mediated by
      IL-18 receptor (IL-18R). When the ligand binds to the IL-18R, IL-18R initiates a
      signaling cascade that results in the activation of nuclear factor kappa B (NF
      kappa B). When mouse EL-4 cells were exposed to IL-18, IL-1 receptor-associated
      kinase (IRAK) was recruited to IL-18R and was phosphorylated. In addition, tumor
      necrosis factor receptor-associated factor-6 (TRAF6) was associated with IRAK.
      Therefore, we concluded that IL-18/IL-18R-mediated signaling may share the
      IRAK/TRAF6 pathway through NF-kappa B activation with the IL-1/IL-1 receptor
      system.

PMID- 9514904
TI  - Two different reactions involved in the primer/template-independent
      polymerization of dATP and dTTP by Taq DNA polymerase.
AB  - Taq and Tth DNA polymerases catalyzed polymerization of dATP and dTTP into poly
      d(A-T) without requiring added primer/template (Hanaki et al., Biochem. Biophys.
      Res. Commun. 238, 113-118), while the Stoffel fragment of Taq DNA polymerase and
      delta Tth DNA polymerase with respective deletions of ca. 290 and 250 N-terminal
      amino acids did not. The primer/template-independent polymerization appeared to
      proceed via two reactions, the slow process of formation of 16-19 nt long oligo
      d(A-T) without primer/template and the rapid process of elongation of the oligo
      d(A-T) by self-priming. As the former step was more sensitive to N-ethylmaleimide
      than the elongation reaction, probably the formation of the oligonucleotide
      preceded the elongation. But when the substrates were depleted, Taq DNA
      polymerase degraded the high molecular weigh d(A-T) polymer to the oligomers
      which were resistant to the further digestion by the 5'-->3' exonuclease activity
      of Taq DNA polymerase. Probably, the elongation and the degradation reactions
      proceeded simultaneously, the former process being faster than the latter in the
      presence of enough dATP and dTTP.

PMID- 9514905
TI  - The protein kinase C activator, phorbol ester, elicits disparate functional
      responses in androgen-sensitive and androgen-independent human prostatic cancer
      cells.
AB  - The protein kinase C (PKC) activator 12-O-tetradecanoyl-phorbol-13-acetate (TPA)
      activated cell death in androgen-sensitive LNCaP cells but not in androgen
      independent DU-145 or PC-3 cells, whose growth was significantly decreased by PKC
      inhibitors staurosporine and H7. All cell lines had similar levels of total PKC
      activities which, however, differed on their dependency on Ca2+ ions and lipid
      and were regulated differently by TPA. Furthermore, expression of the immediate
      early genes c-fos and c-jun was up-regulated by TPA only in LNCaP and DU-145
      cells, whereas PC-3 cells failed to express c-fos mRNA. The regulation of the c
      myc mRNA by TPA correlated inversely with activation of cell death being down
      regulated in LNCaP cells, and slightly increased in the androgen-independent cell
      lines. These results suggest that the PKC signal transduction pathway functions
      differently in androgen-sensitive and insensitive prostatic cells.

PMID- 9514906
TI  - Structure and expression of a novel fibroblast growth factor, FGF-17,
      preferentially expressed in the embryonic brain.
AB  - We isolated the cDNA encoding a novel member (216 amino acids) of the fibroblast
      growth factor (FGF) family from rat embryos. As this protein is the 17th
      documented member of the FGF family, we tentatively termed it FGF-17. We have
      also determined the structures of mouse and human FGF-17 with high amino acid
      identity (100 and 98.6%) to rat FGF-17, respectively. Among FGF family members,
      FGF-17 is most similar (53.7% amino acid identity) to FGF-8. FGF-17 has a typical
      signal sequence at its amino terminus. As expected, recombinant rat FGF-17 was
      efficiently secreted by High Five insect cells infected with recombinant
      baculovirus containing the cDNA indicating that FGF-17 is a secreted protein. FGF
      17 mRNA of approximately 2.1 kb was detected in rat embryos at E14.5, but not at
      E10.5 and E19.5 by Northern analysis. The mRNA was found to be preferentially
      expressed in the neuroepithelia of the isthmus and septum of the rat embryonic
      brain at E14.5 by in situ hybridization. The present results indicate that FGF-17
      might be a novel secreted signaling molecule in the induction and patterning of
      the embryonic brain.

PMID- 9514907
TI  - Bracken fern carcinogenesis: multiple intravenous doses of activated ptaquiloside
      induce DNA adducts, monocytosis, increased TNF alpha levels, and mammary gland
      carcinoma in rats.
AB  - AIMS: (1) establish a rat model for investigating ptaquiloside (PT)
      carcinogenesis via intravenous dosing; (2) determine the role of activated PT
      (APT) in this model; and (3) monitor changes at molecular (DNA adducts, TNF alpha
      levels) and cellular (histopathology) levels. METHODS: Sprague-Dawley rats were
      dosed with PT or APT intravenously for 10 consecutive weeks. One group of animals
      was sacrificed immediately for TNF alpha and DNA adduct analyses. A second group
      of animals was kept alive for 30 more weeks to allow for tumour formation.
      Tissues were collected at the end of the experiment for histopathological
      studies. RESULTS: Rats dosed with PT or APT showed marked increase in monocyte
      and TNF alpha levels. These levels remained high even 30 weeks after the last
      dosing. Analysis of DNA showed the presence of DNA adducts in APT-treated animals
      in target organs. In addition, 40% of APT-treated rats developed mammary gland
      carcinomas. CONCLUSION: This is the first study to demonstrate the potential of
      activated PT as a carcinogen in vivo. In addition, our findings suggest that PT
      exposure can be monitored using monocyte and TNF alpha levels.

PMID- 9514908
TI  - Cadmium inhibits BPDE alkylation of DNA in the major groove but not in the minor
      groove.
AB  - Cadmium, a constituent of tobacco, has the potential to act in synergy with other
      carcinogens in tobacco smoke. Working on the hypothesis that cadmium interactions
      with DNA enhances the mutagenic lesions induced by tobacco carcinogens, we
      investigated the site and sequence selectivity of DNA binding by cadmium using
      DNA reactive chemical probes. Our results show that this divalent cation binds to
      N7 guanines with a great preference for those occurring in runs of G's. Further,
      cadmium considerably diminishes N7 guanine alkylation by the tobacco carcinogen
      metabolite BPDE; however, the biologically relevant guanine alkylation in the
      minor groove by BPDE was not affected. The relevance of our findings to cadmium's
      role in the tobacco carcinogenesis is discussed.

PMID- 9514909
TI  - Infrequent inactivation of DCC gene in replication error-positive colorectal
      cancers.
AB  - Colorectal cancers with and without the replication error (RER) exhibit
      fundamental differences in genotype and phenotype. While alterations in APC, p53,
      and K-ras genes have been characterized between RER+ and RER- colorectal cancers,
      the status of deleted in colorectal carcinomas (DCC) gene has not been yet.
      Alterations of DCC gene were analyzed in stage-matched two panels of 30 RER+ and
      30 RER- colorectal cancers using semiquantitative reverse transcription-PCR and
      PCR-LOH analyses. Loss or reduction of DCC mRNA expression and allelic loss at
      the DCC locus were significantly less frequent in RER+ cancers than in RER-
      cancers. Interestingly, reduced DCC mRNA expression was observed in all 5 RER-
      cancers with liver metastasis. Our results support the concept that RER+ and RER-
      colorectal cancers represent different pathways of carcinogenesis and may give a
      hint for clarifying the specific mechanism of DCC inactivation in RER- colorectal
      cancers.

PMID- 9514910
TI  - Interaction of rat lin-10 with brain-enriched F-actin-binding protein, neurabin
      II/spinophilin.
AB  - We have recently isolated a rat homologue of the Caenorrhabditis elegans lin-10
      product. Although rat lin-10 is expressed in the cytosol and membrane fractions
      of various tissues, it is distributed only in the membrane fraction in brain
      where it is enriched in the synaptic plasma membrane and postsynaptic density
      fractions. We have isolated here a rat lin-10-interacting protein from rat brain
      and identified it to be neurabin-II/spinophilin, which has recently been isolated
      as a protein interacting with protein phosphatase I and F-actin. Neurabin
      II/spinophilin is ubiquitously expressed but enriched in brain, especially in the
      synaptic plasma membrane and postsynaptic density fractions. We discuss the
      physiological significance of the interaction of rat lin-10 with neurabin
      II/spinophilin.

PMID- 9514911
TI  - Arterio-venous carboxyhemoglobin difference suggests carbon monoxide production
      by human lungs.
AB  - Carbon monoxide is hypothesized to be produced by the enzyme heme oxygenase
      predominantly in liver and spleen, bound to hemoglobin, and excreted by the
      lungs. Thus, venous carboxyhemoglobin is expected to be higher or equal to
      arterial carboxyhemoglobin. Unspecific inflammatory stimuli have been shown to
      induce heme oxygenase in lung tissue possibly leading to pulmonary carbon
      monoxide production. Arterial and central venous carboxyhemoglobin levels were
      measured in critically ill patients on the third day of ICU stay (n = 59) as well
      as in otherwise healthy humans prior to orthopedic surgery (n = 29). Arterial and
      central venous carboxyhemoglobin were higher in ICU patients than in healthy
      humans, respectively. In both groups, arterial carboxyhemoglobin was
      significantly higher than central venous carboxyhemoglobin. The arteriovenous
      carboxyhemoglobin differences were similar in both groups. The data suggest (a)
      increased CO-generation in critical illness and (b) pulmonary CO-production in
      healthy and critically ill humans.

PMID- 9514912
TI  - Antioxidant reactions of dihydrolipoic acid and lipoamide with triplet
      duroquinone.
AB  - The oxidation of the antioxidants dihydrolipoate and lipoamide by triplet
      duroquinone (3DQ) has been studied by laser flash photolysis and time-resolved
      resonance Raman (TR3) spectroscopy. Reaction of 3DQ with lipoamide by electron
      transfer [k(H2O)/k(D2O approximately 1] was more rapid than with dihydrolipoate,
      in which a proton is also involved [k(H2O)/k(D2O approximately 2]. For
      dihydrolipoate at neutral pH the undeprotonated form was the major reactive
      species with k approximately 10(9) dm3 mol-1 s-1. At higher pH values the
      reaction of ionised (thiolate) forms was observed with k > or = 4 x 10(9) dm3 mol
      1 s-1. The electron transfer mechanism of reaction between 3DQ and lipoamide was
      confirmed by TR3 spectra in which formation of the durosemiquinone radical anion
      and lipoamide disulfide radical cation (RSS+.) was observed.

PMID- 9514914
TI  - Expression of HuD protein is essential for initial phase of neuronal
      differentiation in rat pheochromocytoma PC12 cells.
AB  - HuD is a neuronal-specific, RNA-binding protein. Here we examined the change in
      the expression of HuD protein during nerve growth factor-mediated differentiation
      of PC12 cells. As cells differentiated and extended neurites, expression of HuD
      gradually increased up to 1.5-fold. When HuD expression was counteracted by
      antisense oligonucleotide, neurite extension was completely inhibited, yet the
      morphology of differentiated cells remained unchanged even after that treatment.
      Furthermore, this morphological change correlated well with the downregulation of
      cyclin-dependent kinase 2 activity. These results suggest that the HuD is
      critically involved in the initial phase of neuronal differentiation.

PMID- 9514913
TI  - Importance of the carboxy-terminus of the CXCR2 for signal transduction.
AB  - The CXCR2 is phosphorylated at the C-terminal intracytoplasmic portion within 15
      sec following the addition of IL-8 or MGSA. Cells transfected with a truncated
      form of the receptor missing the last 12 amino acids (T3) showed normal binding
      affinity, but were no longer phosphorylated; individual alanine replacement
      indicated that Ser346 and 348 were the primary sites of phosphorylation. In
      studies of the importance of phosphorylation in CXCR2 desensitization, cells
      expressing wild type CXCR2 lost GTP gamma S binding above basal rate after the
      first exposure to IL-8, while cells with the T3 mutant retained 60% of their
      capacity to induce GTP gamma S exchange upon a second exposure to IL-8. In
      contrast, receptor internalization was not affected by the loss of
      phosphorylation of the T3 mutant. Further receptor truncation led to decreasing
      binding affinities for IL-8 and MGSA and a decreased rate of GTP gamma S exchange
      following addition of excess ligand which suggests involvement of this region in
      G-protein coupling.

PMID- 9514915
TI  - Serum amyloid P component associates with high density lipoprotein as well as
      very low density lipoprotein but not with low density lipoprotein.
AB  - Serum amyloid P component (SAP) is a glycoprotein in human plasma. We previously
      showed that SAP is specifically localized in human atherosclerotic lesions,
      suggesting that SAP may play a role in atherogenesis. In this study, the
      interactions between human SAP and high density lipoprotein (HDL), low density
      lipoprotein (LDL) and very low density lipoprotein (VLDL) were investigated by
      using a solid phase plate assay. Biotinylated SAP bound to immobilized HDL and
      VLDL in a calcium-dependent, saturable manner. The SAP-HDL and SAP-VLDL bindings
      reached saturation at 4 nM and 16 nM of SAP, respectively. The bindings were
      inhibited by native SAP in a dose-dependent manner. No binding between SAP and
      LDL was found in the presence of calcium or EDTA, which indicates the specificity
      of SAP-lipoproteins interactions. These results suggest that the function of SAP
      is related to its capability to interact with lipoproteins and this may have
      important implications in atherosclerosis and in amyloidosis.

PMID- 9514916
TI  - cDNA cloning, expression, subcellular localization, and chromosomal assignment of
      mammalian aurora homologues, aurora-related kinase (ARK) 1 and 2.
AB  - Chromosomal segregation during mitosis as well as meiosis is considered to be
      regulated by multiple kinases, but the precise mechanism remains largely unknown.
      A mutation in Drosophila, designated aurora, was identified as a responsible gene
      for a chromosomal segregation defect and encodes a putative serine-threonine
      kinase. Here we have identified mammalian aurora homologues, designated aurora
      related kinase (ARK) 1 and ARK2. Kinase domains of murine ARK1 and ARK2 showed 61
      and 62% identity, respectively, to that of aurora at the amino acid levels,
      respectively. Cell cycle analysis revealed that the expression of ARK1 was
      correlated with G2/M phase, while ARK2 was expressed during S and G2/M phases.
      Immunofluorescence analysis demonstrated that ARK2 was mainly localized to the
      midbody, while ARK1 has been reported to be localized to the spindle pole during
      mitosis. Collectively, these results suggest that these two kinases may have
      distinct roles with different expression timing and subcellular localization
      during the cell cycle progression. Interspecific backcross mapping revealed that
      Ark1 is located in a distal region of mouse chromosome 2, while Ark2 is located
      in a central region of mouse chromosome 11.

PMID- 9514917
TI  - Functional coupling of secretion and capacitative calcium entry in PC12 cells.
AB  - The caffeine-evoked effects on the intracellular Ca2+ concentration ([Ca2+]i) and
      on the release of dopamine by PC12 cells were investigated. Stimulation by
      caffeine resulted in a transient Ca2+ release which was followed by a sustained
      phase of Ca2+ entry through a non-voltage dependent pathway. Treatment with
      cyclopiazonic acid (CPA) or thapsigargin, inhibitors of the Ca2+ ATPase pump of
      the endoplasmic reticulum, resulted in only a sustained rise in [Ca2+]i in the
      presence of extracellular Ca2+. Pretreatment of cells with CPA or thapsigargin
      abolished the subsequent Ca2+ responses to caffeine. Caffeine also evoked the
      release of dopamine from the cells only in the presence of extracellular Ca2+,
      which was mimicked by CPA. These results suggest that store-dependent Ca2+ entry
      evoked by caffeine has an indispensable role in the secretory response in an
      excitable cell line, PC12 cells.

PMID- 9514918
TI  - Cloning and functional expression of a new aquaporin (AQP9) abundantly expressed
      in the peripheral leukocytes permeable to water and urea, but not to glycerol.
AB  - A new member (AQP9) of the aquaporin family was identified from human leukocytes
      by homology cloning using PCR. A full length clone was obtained by screening
      human liver cDNA library. AQP9 encodes a 295-amino-acid protein with the amino
      acid sequence identity with AQP3 (48%), AQP7 (45%), and other aquaporins
      (approximately 30%), suggesting that AQP3, AQP7, and AQP9 belong to a subfamily
      of the aquaporin family. Injection of AQP9-cRNA into Xenopus oocytes stimulated
      the osmotic water permeability 7-folds with a low activation energy (4.2
      kcal/mol) which was inhibited by 0.3 mM mercury chloride by 48%. AQP9 also
      facilitated urea transport 4-folds. However, in contrast to AQP3 and AQP7, AQP9
      did not stimulate the glycerol permeability, suggesting a unique permeability
      character. Northern blot analysis revealed the high expression of 3.5-kb messages
      in peripheral leukocytes >> liver > lung = spleen, but not in thymus. The
      possible role of AQP9 in the immunological function of leukocytes is intriguing
      and the identification of AQP9 with unique permeability profile may expand our
      understanding of water and small solute transport in the body.

PMID- 9514919
TI  - Detection of the asialoglycoprotein receptor on cell lines of extrahepatic
      origin.
AB  - The asialoglycoprotein receptor (ASGPR) is the first lectin discovered in
      mammals. Despite its significant biological role in binding and internalization
      of desialyated glycoproteins, at least in the human, little information is
      available regarding its tissue distribution outside of the liver. In the present
      study, antibodies were raised against the H1 major subunit of the human ASGPR
      using synthetic peptide antigens, and their binding specificity confirmed by
      enzyme linked immunosorbent assay. Cell surface analysis by fluorescence
      activated flow cytometry on various human tissue cell lines confirmed the liver
      parenchymal cells as the major expression site of ASGPR. Nonetheless, ASGPR was
      also detectable on some extrahepatic cells such as the Jurkat T-cell line. The
      determination of extrahepatic expression of ASGPR will have consequences in
      analyzing the biological role of this receptor complex as well as having
      implications in designing ASGPR mediated drug- or gene-delivery strategies.

PMID- 9514920
TI  - Structural specificity of polyamines and polyamine analogues in the protection of
      DNA from strand breaks induced by reactive oxygen species.
AB  - Reactive oxygen species are known to induce strand breaks and/or base
      modifications in DNA. DNA strand breaks are associated with many pathologies and
      programmed cell death. We have examined the ability of the polyamines and their
      analogues to protect phi X-174 plasmid DNA from strand breakage induced by a
      oxygen-radical generating system. Spermine and several unsymmetrically
      substituted polyamine analogues reduced the amount of strand breakage at a
      physiologically relevant concentration of 1 mM. However, putrescine, spermidine,
      N1-acetylspermine, N1-acetylspermidine and symmetrically alkylated polyamine
      analogues were not able to reduce strand breakage at the same concentration.
      Thus, the unsymmetrically alkylated polyamine analogues and natural spermine can
      protect DNA against strand breakage induced by Cu(II)/H2O2 generated ROS similar
      to other more classical antioxidants.

PMID- 9514921
TI  - Adrenomedullin stimulates interleukin-6 production in Swiss 3T3 cells.
AB  - Adrenomedullin (AM) has very recently been demonstrated to be produced and
      secreted from fibroblasts. The production of AM in the fibroblasts is augmented
      by inflammation-related substances, and Swiss 3T3 fibroblast cells express AM
      specific receptors coupled with adenylate cyclase. To assess the functions of AM
      secreted from fibroblasts, we measured the effect of AM on production in Swiss
      3T3 cells of interleukin-6 (IL-6), a typical cytokine involved in the general
      inflammatory reactions. AM stimulated basal secretion of IL-6 5.5-fold, while
      other peptides elicited much weaker stimulatory effects. The effect of AM was
      inhibited with an AM receptor antagonist and a cAMP-dependent protein kinase
      (PKA) inhibitor. Furthermore, AM remarkably potentiated stimulatory effects of
      tumor necrosis factor-alpha, IL-1 beta and lipopolysaccharide on IL-6 production.
      This stimulatory effect of AM was induced through activation of gene
      transcription, which reached maximum within 30 min. These findings verify that AM
      is a rapid and extraordinarily potent regulator of IL-6 production in Swiss 3T3
      cells acting through the cAMP-PKA pathway. The data thus obtained suggest that AM
      is a peptidergic regulator of inflammation.

PMID- 9514922
TI  - PPADS inhibits P2Y1 purinoceptors in rat brain capillary endothelial cells and in
      rat ileal myocytes by an indirect mechanism.
AB  - P2Y1 receptor-like responses were analyzed in rat ileal myocytes and in rat brain
      capillary endothelial cells. In endothelial cells, pyridoxal phosphate-6
      azophenyl-2',4'disulfonic acid (PPADS) inhibits ADP induced intracellular Ca2+
      transients with a half maximum effect at 3 microM. PPADS shifts ADP dose response
      curves to larger concentrations. Yet PPADS is inactive when added at the same
      time as ADP. A preequilibration of the cells with PPADS is necessary to observe
      its inhibitory action. Similarly in ileal myocytes, PPADS has no action on ADP
      responses when it is applied at the same time as ADP. Actions of PPADS require a
      preequilibration with the cells and are fully reversible. These results suggest
      that PPADS is not a competitive antagonist of P2Y1 receptors and caution about
      its usefulness to distinguish subtypes of P2Y1 receptors.

PMID- 9514923
TI  - Exoenzyme S from P. aeruginosa ADP ribosylates rab4 and inhibits transferrin
      recycling in SLO-permeabilized reticulocytes.
AB  - ADP-ribosylation of rab proteins by exoenzyme S (Exo S) of P. aeruginosa was
      studied using reticulocytes. 14-3-3 protein, the eukaryotic cofactor that is
      obligatory for Exo S activity, was found in association with reticulocyte
      endocytic vesicles and exosomes, vesicles previously shown to be enriched with
      rab4. Incubation of purified endocytic vesicles with Exo S triggered rab4 ADP
      ribosylation. Transferrin recycling in SLO-permeabilized reticulocytes was highly
      impaired when Exo S was added to the cells, suggesting that ADP-ribosylation
      affected rab4 function. Moreover, in vitro ADP-ribosylation of different rab
      proteins was studied using the cofactor activity extracted from reticulocytes.

PMID- 9514926
TI  - Biochemical evidence for oligomerization of rat adrenal acyl-coenzyme
      A:cholesterol acyltransferase.
AB  - Acyl-coenzyme A:cholesterol acyltransferase (ACAT) in rat adrenal was compared
      with that in rat liver. Immunoblot analyses of the microsomal fractions from
      adrenal with an anti-human ACAT antibody detected a 45 kDa protein. Upon
      pretreatment of these microsomal fractions with chemical cross-linkers such as
      BS3 and Sulfo-EGS, the 45 kDa band decreased with a concomitant increase in high
      molecular weight proteins (55, approximately 100, and approximately 230 kDa),
      suggesting that ACAT constitutes oligomers of 45 kDa monomers associated with a
      10 kDa protein. In sharp contrast, the same immunoblot analysis of rat liver
      microsomal fractions identified a 50 kDa protein which was not cross-linked by
      these cross-linkers. Moreover, when four ACAT inhibitors were tested for their
      effects on adrenal and liver enzymes, NTE-122, CI-976, and E5324 were more
      effective for the liver enzyme, whereas 58-035 was much more effective for
      adrenal ACAT. These biochemical and pharmacological observations support the
      notion that the rat liver ACAT protein is distinct from the adrenal counterpart.

PMID- 9514927
TI  - Inhibition by imipramine of ATP-evoked responses in rat pheochromocytoma cells.
AB  - The effect of imipramine on the ATP-evoked release of dopamine was analyzed in
      parallel with its effects on the rise in the intracellular Ca2+ concentration
      ([Ca2+]i) and current induced by ATP in rat pheochromocytoma PC12 cells.
      Imipramine (10-300 microM) inhibited the ATP-evoked release of dopamine and rise
      in [Ca2+]i in a concentration-dependent fashion though the effect of imipramine
      on the release was slightly more obvious. Imipramine also inhibited the ATP
      activated inward current at a similar concentration range. These results show a
      new pharmacological profile of imipramine, namely the inhibition of P2X2
      receptors.

PMID- 9514928
TI  - Molecular cloning and characterization of a novel protein kinase C-interacting
      protein with structural motifs related to RBCC family proteins.
AB  - A novel protein kinase C (PKC)-interacting protein was identified by the yeast
      two-hybrid screening using the regulatory domain of PKC beta I as a bait. The
      protein contained several structural motifs such as two putative coiled-coil
      regions, a RING-finger, a B-box, and a B-box-like motif in the order from NH2- to
      COOH-terminals. The molecular organization of the protein resembles the structure
      of the RBCC protein family proteins which usually have a RING-finger, a B-box,
      and a coiled-coil region. Therefore, the protein identified was designated as
      RBCK1 (RBCC protein interacting with PKC 1). Northern blot analysis showed that
      RBCK1 gene is expressed ubiquitously among rat tissues. RBCK1 protein associated
      with PKC beta I and PKC zeta when coexpressed in cultured mammalian cells. By the
      polymerase chain reaction-assisted DNA-binding site selection and the
      electrophoretic mobility shift assay, RBCK1 protein was shown to bind to several
      DNA fragments containing TGG-rich sequences. When the yeast GAL4 DNA-binding
      domain fused RBCK1 protein was expressed in COS-7 cells harboring the luciferase
      gene placed under a synthetic promoter containing GAL4-binding sites, the fusion
      protein showed enhanced transcriptional activity comparing with the GAL4 DNA
      binding domain. These results suggest that RBCK1 protein might be a transcription
      factor that has a role in the signaling pathway through PKC.

PMID- 9514929
TI  - Antibody to a Helicobacter pylori species specific antigen in patients with
      adenocarcinoma of the stomach.
AB  - This study attempted to identify a possible antibody response to Helicobacter
      pylori, which is associated with patients with adeno-carcinoma of the stomach. By
      using proteins of H. pylori as the antigen, pooled sera from gastric cancer and
      non-cancer patients were used as the first antibody for Western blot analysis.
      Antibody responses to a 26 kD secreted protein were observed in pooled cancer
      sera, but not in pooled sera from non-cancer patients. The protein was purified,
      while amino acid sequences revealed that it was a H. pylori species specific
      protein. The gene of this protein was cloned and a recombinant protein was
      expressed in E. coli. In addition, an antibody to the recombinant protein was
      tested in each individual patient using Western blot analysis. None of the forty
      non-gastric cancer patients were positive for the antibody to the recombinantly
      expressed 26 kD species specific protein. Meanwhile, six of the twenty four
      cancer patients tested positive (0/40 vs 6/24, p < 0.01). Results presented
      herein demonstrate that the species specific protein of H. pylori can be useful
      in detecting H. pylori associated with adenocarcinoma of the stomach.

PMID- 9514930
TI  - Physiological role of the association complexes of alpha-crystallin and its
      substrates on the chaperone activity.
AB  - Previous reports on the chaperone activity of alpha-crystallin to prevent protein
      denaturation and thermal aggregation have suggested that partially denatured
      proteins can bind alpha-crystallin in its central region. Likewise, beta- and
      gamma-crystallin can also be localized to the central cavity of alpha-crystallin
      particle in vivo, which provides indirect evidence that alpha-crystallin can
      function as a chaperone in the intact lens. In this study, we have further
      demonstrated that the binding of the substrate proteins to alpha-crystallin by
      short-term preincubation may mimic the in vivo conditions of crystallin
      association. Preheating of alpha-crystallin with its substrate proteins at 60
      degrees C for 20 min resulted in the formation of stable complexes between alpha
      crystallin and its substrates (8.0% of insulin or 5.3% of gamma-crystallin was
      involved in complex formation). Under such conditions, the chaperone activity of
      alpha-crystallin to inhibit dithiothreitol-, ultraviolet-, or oxidation-induced
      protein aggregation can be greatly enhanced. Since UV-irradiation and oxidative
      stress are common insults to eye lenses under normal physiological conditions,
      the presence of alpha/gamma and alpha/beta complex in vivo may play an important
      role to maintain the lens in a transparent state.

PMID- 9514931
TI  - Interaction of the second coding exon of Tat with human EF-1 delta delineates a
      mechanism for HIV-1-mediated shut-off of host mRNA translation.
AB  - HIV-1 Tat has pleiotropic functions. While its most studied role is to activate
      transcription from the retroviral long terminal repeat (LTR)-promoter, Tat also
      has functions as a secretable growth factor, a T-cell activator, and an inducer
      of cellular apoptosis, amongst others. For its transcriptional function, the
      first coding exon of Tat appears wholly sufficient; however, lentiviruses (HIVs
      and SIVs) maintain and conserve a second coding exon for Tat. While the
      function(s) of the second exon of Tat has remained largely unknown, its integrity
      in lentiviral genomes suggests biological importance, possibly a role in non
      transcriptional activities. To understand better the biology of the second exon
      of Tat in HIV-1 infection of cells, we have searched for cellular proteins that
      bind specifically to this protein domain. Here, we report that the human
      translation elongation factor 1-delta (EF-1 delta) binds to the second exon of
      HIV-1 Tat. Interaction between Tat and EF-1 delta dramatically reduces the
      efficiency of the translation of cellular, but not viral, mRNAs. These findings
      suggest that a non-transcriptional activity of Tat modulates cellular protein
      synthesis, thereby affecting the metabolism of host cells.

PMID- 9514932
TI  - Definition of the protein kinase C interaction site of phospholipase D.
AB  - Serial deletions of the N-terminal 319 amino acids of rPLD1 expressed in COS-7
      cells resulted in increased basal PLD activity. Incubation of the cells with
      phorbol myristate acetate increased the activity of endogenous and wild-type
      rPLD1. The mutant rPLD1 with deletion of the first 50 amino acids responded to
      the phorbol ester, however, rPLD1 with deletions of 115 amino acids or more did
      not. In cells in which constitutively active V14RhoA was co-expressed with the
      mutant PLDs, stimulation of PLD activity was observed with all deletion mutants.
      In membranes from COS-7 cells in which the mutant PLDs were expressed, only the
      mutant with deletion of 50 N-terminal amino acids responded to added protein
      kinase C-alpha and phorbol ester, in agreement with the in vivo studies. When
      myristoylated ADP-ribosylation factor 3 (mARF3) was added together with guanosine
      5'-3-O-(thio)triphosphate, all mutants showed stimulation of PLD activity. It is
      concluded that the site of interaction of protein kinase C with rPLD1 is located
      in the N-terminal region and that Rho and ARF interact at other sites.

PMID- 9514933
TI  - Insulin acts intracellularly on proteasomes through insulin-degrading enzyme.
AB  - Insulin decreases cellular protein degradation, but the mechanism of this action
      is poorly understood. We have shown that insulin can have an inhibitory effect on
      the action of the proteasome in vitro, which requires the presence of insulin
      degrading enzyme (IDE). In this study we have used an antibody which inhibits the
      activity of IDE to show that IDE is required for insulin inhibition of protein
      degradation in intact cells. The anti-IDE antibody blocked the insulin effect on
      cellular degradation of proteins prelabeled with radioactive amino acids. The
      anti-IDE antibody also decreased insulin inhibition of proteasome degradation of
      a specific substrate in intact cells. These data suggest that insulin works
      intracellularly via IDE to inhibit protein degradation by the proteasome. Thus,
      IDE may function as an intracellular mediator for insulin effects on protein
      degradation. This is a novel signal transduction mechanism for peptide hormones.

PMID- 9514934
TI  - Preliminary analysis of the transcriptional regulation of the human beta 1
      adrenergic receptor gene.
AB  - One open reading frame of a 13 kb genomic clone of the human beta 1-adrenergic
      receptor, which lacks introns, encodes the previously isolated cDNA.
      Transcript(s) between 4.7 and 5.1 kb are detected in total RNA, whereas a
      approximately 3 kb transcript is detected only in polyadenylated RNA. The poly
      (A+) transcript is most highly expressed in the pancreas, liver, heart, kidney,
      thalamus, adrenal, and salivary glands. Primer extension and ribonuclease
      protection analyses suggest that the major transcriptional start site is located
      at -263. Transient expression of luciferase reporter gene constructs indicates
      that the region from -444 to -360 possesses the primary promoter, consistent with
      the transcriptional start site at -263. Negative transcriptional regulatory
      elements are located from -3118 to -2730 and -2730 to -2241, while a positive
      element is located between -2241 and -1790. The present study suggests that,
      despite similarities, the expression and transcriptional regulation of the human
      gene are distinct from those of the genes of other species.

PMID- 9514935
TI  - Like p53, the proliferation-associated protein p120 accumulates in human cancer
      cells following exposure to anticancer drugs.
AB  - Accumulation of p53 protein following DNA damage is independent of transcription;
      in turn, p53 transcriptionally induces other proteins. Herein we demonstrated
      that p120, a proliferation-associated protein, was induced by DNA-damaging and
      microtubule-active drugs in human cancer cells. However, induction of p120 was
      independent of p53; and expression of exogenous wt p53 induced p21WAF1/CIP1 but
      not p120, excluding p120 as a transcriptional target of p53. Like p53, induction
      of p120 by anticancer drugs did not require transcription. Induction of p120 by
      actinomycin-D occurred at concentrations which inhibit RNA synthesis and p120
      mRNA levels. Inhibition of proteasomes resulted in accumulation of higher
      molecular weight proteins, reacting with anti-p120 antibodies. This suggests that
      the mechanisms of p120 and p53 induction are similar and involve inhibition of
      degradation. p120 protein stabilization represents an expedient means for
      accumulation of key response proteins following exposure to cytotoxic agents.

PMID- 9514936
TI  - No effect of fibrates on synthesis of apolipoprotein(a) in primary cultures of
      cynomolgus monkey and human hepatocytes: apolipoprotein A-I synthesis increased.
AB  - Fibrates have been shown to decrease plasma levels of triglyceride-rich
      lipoproteins and LDL and to increase HDL. Data on the effect of fibrates on
      lipoprotein(a) levels in man are not consistent. Because lp(a) levels in vivo are
      mainly regulated at synthesis level, we studied the effect of fibrates on the
      synthesis of apolipoprotein(a) (apo(a)) in primary cultures of cynomolgus monkey
      and human hepatocytes. Furthermore, we assessed the effect of fibrates on
      apolipoprotein A-I (apo A-I) synthesis and investigated whether different
      fibrates have different effects on the apo(a) and apo A-I synthesis. The addition
      of gemfibrozil to cultures of monkey and human hepatocytes had no effect on
      apo(a) synthesis, but resulted in a dose- and time-dependent increase of apo A-I
      synthesis and mRNA. In simian hepatocytes maximal stimulation was 2.5-fold after
      incubation for 72 h with 1.0 mM gemfibrozil, whereas apo A-I synthesis was
      induced 1.8- and 2.0-fold by using 0.1 mM and 0.3 mM, respectively. Similar
      results were obtained by using human hepatocytes; apo(a) synthesis remained
      unchanged, while apo A-I secretion was 2.0-fold increased at 1 mM gemfibrozil.
      Other fibrates like bezafibrate, clofibrate and clofibric acid did not change
      apo(a) synthesis either. In contrast, they enhanced the synthesis of apo A-I (1.5
      , 1.8- and 1.8-fold, respectively), although less potently than gemfibrozil. We
      conclude that fibrates have no effect on apolipoprotein(a) synthesis in monkey
      and human hepatocytes and that these drugs induce apo A-I synthesis.

PMID- 9514937
TI  - The rapid inhibitory effect of glucocorticoid on cytosolic free Ca2+ increment
      induced by high extracellular K+ and its underlying mechanism in PC12 cells.
AB  - The effect of glucocorticoid(GC) on peak cytosolic free calcium net increment
      (delta[Ca2+]i) induced by high-K+ was detected with MiraCal Image System. The
      main results were as follows: (1) Corticosterone(B) could inhibit delta[Ca2+]i in
      a time-dependent and concentration-dependent manner. (2) The inhibitory effect of
      B could be mimicked by bovine-serum albumin conjugated corticosterone (B-BSA)
      also in a dose-dependent manner. (3) G-protein inhibitor, either PTX or GDP beta
      S significantly reduced the inhibitory effect of B and B-BSA on delta[Ca2+]i (4)
      PMA, a stimulator for protein kinase C(PKC), could inhibit delta[Ca2+]i. (5)
      Although the inhibitors of PKC, chelerythrine chloride and bisindolylamide I per
      se had no influence on delta[Ca2+]i, but they significantly antagonized the
      inhibitory effect of B and B-BSA on delta[Ca2+]i. It is postulated that GC
      inhibit delta[Ca2+]i induced by high-K+ through a membrane mechanism and by a
      pathway involving G-protein and PKC.

PMID- 9514938
TI  - GS4071 is a slow-binding inhibitor of influenza neuraminidase from both A and B
      strains.
AB  - The kinetics of inhibition of purified influenza neuraminidases from A/Tokyo/3/67
      and B/Memphis/3/89 influenza viruses by (3R,4R,5S)-4-acetamido-5-amino-3-(1
      ethylpropoxy)-1-cyclohexene- 1-carboxylic acid (GS4071) were investigated.
      Progress curve experiments established that GS4071 is a time dependent inhibitor
      of both A and B strains of influenza neuraminidase. The apparent association and
      dissociation rate constants, as well as the overall Ki values, were only modestly
      different for the two neuraminidase strains. The time dependent inhibition
      phenomenon, often referred to as slow-binding inhibition, appears to be a
      consequence of the very slow rate of dissociation of the compound from influenza
      neuraminidase.

PMID- 9514939
TI  - Structure and transcriptional function of the 5'-flanking region of rat
      thromboxane receptor gene.
AB  - We cloned a cDNA for rat TX receptor, and observed its expression in the kidney,
      including vascular smooth muscle. The aim of the present study was to clone the
      5'-flanking region (5'-FL) of rat TX receptor gene, and to examine its
      transcriptional gene expression regulation. The 5'-FL was cloned by a PCR method,
      and the nucleic acid structure of 5'-FL (approximately 1 Kb) was disclosed. The
      transcription initiation site was shown to be 63 bases upstream of the 5' end of
      the cDNA by the primer extension. In the 5'-FL, putative AP-1 binding sites,
      glucocorticoid-responsive elements, NF-kappa B binding sites, GATA box, and shear
      stress-responsive elements were identified. The 5'-FL was then fused upstream of
      firefly luciferase cDNA in an expression vector, and we examined its
      transcriptional activity in transiently transfected cultured vascular smooth
      muscle cells (VSMC). Luciferase expression was dependent on the length of 5'-FL,
      and it was significantly stimulated by phorbol 12-myristate 13-acetate (PMA),
      dexamethasone (Dex), tumor necrosis factor-alpha, and interleukin (IL). By a semi
      quantitative RT-PCR method, TX receptor mRNA was shown to be induced by Dex, IL
      6, and PMA in cultured VSMC. In conclusion, we have revealed the structure of
      transcription regulatory region of TX receptor. Expression of TX receptor gene is
      possibly up-regulated by activation of protein kinase C, glucocorticoid excess,
      and IL-6, in vascular smooth muscle.

PMID- 9514940
TI  - Insertional mutagenesis in the tailspike protein of bacteriophage P22.
AB  - The tailspike protein (TSP) of bacteriophage P22 is a homotrimeric
      multifunctional protein responsible for recognition and hydrolysis of Salmonella
      typhimurium host receptors. Once properly folded, TSP shows an unusual stability
      to temperature and detergent denaturation, prompting the analysis of TSP as a
      framework for the positioning of heterologous protein segments. We have explored
      the flexibility of inner sites and both amino and carboxy termini to accommodate
      foreign peptides for phage display. In the examined inner sites, TSP is extremely
      sensitive to minor sequence modifications, the folding intermediates being
      rapidly degraded. However, both the amino and carboxy termini are tolerant to
      peptide fusions, rendering stable and functional chimeric proteins. Surprisingly,
      the amino terminus, which connects the tail to the neck structure, can accept
      large peptide fusions, and the foreign amino acid stretches are solvent-exposed
      and highly antigenic on assembled, infectious virus particles.

PMID- 9514941
TI  - Differential expression of proteins during healing of cutaneous wounds in
      experimental normal and chronic models.
AB  - Recent studies have demonstrated growth factors and other cellular proteins as
      being important in the healing process. In this study, we have investigated the
      differential expression of proteins in wound tissues of normal and chronic animal
      models. Proteins were identified by specific antibodies, partial N-terminal amino
      acid sequence, and molecular weight homology. In normal wound tissues de novo
      synthesis of a heat shock protein, platelet derived growth factor (PDGF), and
      fibroblast growth factor (FGF) was induced within 24 h of skin injury. Proteins
      resembling vascular endothelial growth factor, receptors for PGDF, FGF, and
      epidermal growth factor, were synthesized. The elevated synthesis declined to a
      basal level in 7 to 14 days after skin injury which coincided with healing of
      wounds. These changes occurred only in wound site tissues but not in distal
      tissues. In contrast, the chronic wounds presented a different picture. The
      expressions of these proteins were either delayed or inhibited. This suggested
      the role of these proteins during normal and chronic wound healing. The proteins
      which were down regulated in chronic wounds may be used in the management of
      wounds and exploited as targets for therapeutic development.

PMID- 9514942
TI  - Isolation and expression analysis of peanut chlorotic streak caulimovirus (PClSV)
      full-length transcript (FLt) promoter in transgenic plants.
AB  - A promoter fragment from peanut chlorotic streak caulimovirus (PClSV) full-length
      transcript (FLt) was identified and later modified to have duplicated enhancer
      domain. The FLt promoter with its single or double enhancer domains, fused with
      the GUS reporter gene to form chimeric gene constructs, showed a high level of
      expression of these genes in cells and transgenic plants. The FLt promoter with
      its double enhancer domain gives an average threefold greater expression of genes
      compared to the FLt promoter with its single enhancer domain in transgenic
      plants. In young seedlings the expression was in the order root > leaf > stem.
      The histochemical GUS assay in young seedlings showed more activity in root tips
      and leaf midribs, veins, and other vascular tissues. The expression from the
      PClSV FLt promoter was compared with that from the figwort mosaic virus promoter
      in transgenic plants. These constitutive promoters were comparable in respect to
      GUS expression level.

PMID- 9514943
TI  - Regulation of tight junction permeability and occludin expression by
      polyunsaturated fatty acids.
AB  - Tight junctions (TJ) are the topical most structure in epithelial and endothelial
      cells and play a key role in the control of permeability and prevention of tumour
      cell invasion of endothelium. In this study we examined the effects of a range of
      polyunsaturated fatty acids on the function of TJs and the expression of
      occludin, a key molecule in the TJs of the human vascular endothelial cell line,
      ECV304. Treatment of the endothelial cells with gamma linolenic acid, an anti
      cancer PUFA, increased the transendothelial cell resistance (TER) and reduced the
      paracellular permeability to large molecules. The effects were seen without any
      changes in the viability of the endothelial cells. Occludin, a recently
      identified molecule, which plays a major role in tight junctions was up-regulated
      by this fatty acid as revealed by both Western blotting and immunofluorescence.
      Other fatty acids were also tested. Eicosapentaenoic acid (EPA) also exerted an
      up-regulatory effect, but LA and AA down-regulated the expression. We conclude
      that GLA and EPA which also have other anti-cancer effects, regulate the
      expression of occludin in endothelial cells and thus contribute to the
      modification of the TER of these cells.

PMID- 9514944
TI  - Bromocriptine modulates P-glycoprotein function.
AB  - The multidrug resistance (MDR)-associated P-glycoprotein (P-gp) is a membrane
      transporter which carries, at the expense of MgATP hydrolysis, many amphiphilic
      molecules, such as the MDR-related cytotoxic drugs vincristine and vinblastine,
      and the MDR-reversing agents verapamil and progesterone. We have tested the
      effects on P-gp function of bromocriptine (BCT), an ergot alkaloid known as a D2
      dopaminergic receptor agonist. BCT (at 4 microM) partially reverses the P-gp
      mediated vincristine resistance of the Chinese hamster lung fibroblasts DC
      3F/ADX, a MDR cell line. P-gp containing membrane vesicles prepared from the DC
      3F/ADX cells exhibit, in the absence of any added drug, a basal MgATPase activity
      due to P-gp. BCT inhibits this basal ATPase activity, with a half-inhibiting
      concentration of 0.30 +/- 0.15 microM. BCT also inhibits the verapamil-induced P
      gp ATPase stimulation competitively (Ki approximately 0.2 microM), and the
      progesterone-induced P-gp ATPase stimulation non-competitively (Ki approximately
      0.07-0.10 microM). BCT also non-competitively inhibits the vinblastine-dependent
      P-gp ATPase activity within the same concentration range. Hydroxylated
      metabolites of BCT have different effects on P-gp ATPase, only the
      monohydroxylated being able to modulate both the basal and the drug-stimulated
      ATPase activities. In conclusion, these effects of BCT on P-gp function can be
      linked to a specific interaction with P-gp, probably involving inhibition of P-gp
      mediated drug transport.

PMID- 9514945
TI  - cAMP enhances CSF-1-induced ERK activity and c-fos mRNA expression via a MEK
      dependent and Ras-independent mechanism in macrophages.
AB  - Inhibition of MAPK by elevated intracellular cAMP has often been correlated with
      suppression of growth factor-induced proliferation. However, in murine bone
      marrow-derived macrophages (BMM) we show that the cAMP analogue, 8-bromo cAMP
      (8BrcAMP) (1mM), despite being a dramatic G1 phase proliferation inhibitor,
      increased ERK activity both in the absence and presence of CSF-1; these increases
      were blocked by PD98059 (100 microM) suggesting MEK dependence. In contrast, CSF
      1-stimulated p21Ras activity was blocked by 8BrcAMP thus correlating with the
      inhibition of proliferation. This is the first report to indicate that elevated
      intracellular cAMP can activate ERK activity while inhibiting proliferation and
      the data support the concept in CSF-1-treated macrophages of Ras-independent
      activation of ERK activity. It was also found that the acute but not the
      sustained elevation of c-fos mRNA expression due to 8BrcAMP was also MEK
      dependent indicating that there are separate pathways controlling c-fos mRNA
      expression in BMM.

PMID- 9514946
TI  - Mouse PRL-2 and PRL-3, two potentially prenylated protein tyrosine phosphatases
      homologous to PRL-1.
AB  - Protein tyrosine phosphatases (PTPs) play a fundamental role in regulating
      diverse cellular processes. PRL-1 is a unique nuclear PTP that is induced in
      mitogen-stimulated cells and regenerating liver. Database searches using the PRL
      1 sequence led to the identification of mouse PRL-2 and PRL-3 which exhibit 87%
      and 76% identity to mouse PRL-1 in their amino acid sequences. All three mouse
      PRL proteins contain a C-terminal consensus sequence for prenylation. All PRL
      proteins bear significant sequence homology to Cdc14p and the recently identified
      tumor suppressor PTEN/MMAC1, in regions other than the conserved PTP signature
      motif. The nucleotide sequences of the coding regions of mouse PRL-2 and PRL-3
      are, respectively, 71% and 62%, identical to mouse PRL-1, while the 5' un
      translated regions of mouse PRL-1, PRL-2, and PRL-3 are much more divergent.
      Northern blot analysis revealed that PRL-2 is preferentially expressed in
      skeletal muscle, while PRL-3 is preferentially expressed in both skeletal muscle
      and heart, although both PRL-2 and PRL-3 are expressed at lower levels in other
      tissues.

PMID- 9514947
TI  - The Byr2 kinase translocates to the plasma membrane in a Ras1-dependent manner.
AB  - The activation of mitogen-activated protein kinase cascades by the Ras GTPase is
      an evolutionarily conserved signal transduction mechanism. To better understand
      the interaction between Ras and its target kinase, we study the yeast
      Schizosaccharomyces pombe where the Ras1 GTPase activates the Byr2 kinase. Cell
      fractionation and immunofluorescence showed that Ras1 was localized to the plasma
      membrane and that Byr2 was in the cytoplasm. When Ras1 was overexpressed, Byr2
      was translocated to the plasma membrane. Byr2 translocation was dependent on
      binding to Ras1 since Ras1-V12, an activated mutant of Ras1, caused more Byr2
      translocation than Ras1, since Ras1-D38E, an effector domain mutant, did not
      cause Byr2 translocation, and since the Ras1-binding domain of Byr2 was necessary
      and sufficient to cause Byr2 translocation. The Byr2 protein was usually not
      uniform around the plasma membrane, but was frequently enriched at the cell ends
      and at the region of septal deposition. This uneven membrane localization
      depended upon regions of the Byr2 regulatory domain, in addition to those
      required for Ras1 binding, suggesting that these Byr2 domains participate in
      protein-protein interactions.

PMID- 9514948
TI  - Cloning and characterization of a novel class II phosphoinositide 3-kinase
      containing C2 domain.
AB  - Phosphoinositide 3-kinases (PI3Ks) have been shown to play critical roles in cell
      growth, differentiation, survival, and vesicular transport. Class II PI3Ks have
      been recently identified in mouse and human (PI3K-C2 alpha/m-p170/m-cpk and HsC2
      PI3K) and in Drosophila (PI3K 68D/cpk) which contain C2 domain at the C-terminus.
      However, their physiological function is largely unknown. We report here cloning
      and characterization of murine PI3K-C2 gamma, a novel class II PI3K. The
      catalytic domain as well as C2 domain are highly conserved in the Class II PI3K
      family, while the N-terminal regions of these proteins share little similarity.
      Unlike other Class II PI3Ks, PI3K-C2 gamma exclusively expressed in the liver,
      and a N-terminal truncated form was found in lung and a certain hematopoietic
      cell line. Specific antiserum against PI3K-C2 gamma precipitated PI3K activity
      from the membrane fraction of mouse liver but not from heart. Recombinant PI3K-C2
      gamma exhibited a restricted lipid substrate specificity; it phosphorylated
      phosphatidylinositol (PtdIns) and PtdIns4P but not PtdIns(4,5)P2. Deletion
      mutations revealed that both the N-terminal region and the C2 domain were
      critical for enzymatic activity. The murine PI3K-C2 gamma gene locus was mapped
      to the distal region of mouse chromosome 6 in a region of homology with human
      chromosome 12p, which is distinct from the position of HsC2-PI3K. Cloning and
      biochemical characterization of the third member of class II PI3Ks provide a new
      insight into the function of this subfamily of PI3Ks.

PMID- 9514949
TI  - The LEC rat possesses reduced hepatic selenium, contributing to the severity of
      spontaneous hepatitis and sensitivity to carcinogenesis.
AB  - The hepatic concentrations of copper, zinc, magnesium, calcium, and selenium were
      measured in LEC rats, which develop a spontaneous form of hepatitis at 3-4 months
      of age, and compared to trace metal concentrations in the LEA rat, its
      asymptomatic congenic strain. Consistent with results found by other groups,
      copper was found to accumulate within the liver of LEC rats to levels more than
      50 times those measured in LEA rats. In addition, liver selenium concentration in
      LEC rats was found to be around 50% of that in LEA rats. The enzyme activity, and
      RNA for the selenium dependent enzyme, glutathione peroxidase, was also found to
      be reduced in LEC rat liver. These results indicate that hepatic selenium in the
      LEC rat is depleted and that, as a result of this, the capacity to protect cells
      from copper-induced free-radical damage is reduced.

PMID- 9514950
TI  - Ammodytin L, an inactive phospholipase A2 homologue with myotoxicity in mice,
      binds to the presynaptic acceptor of the beta-neurotoxic ammodytoxin C in
      Torpedo: an indication for a phospholipase A2 activity-independent mechanism of
      action of beta-neurotoxins in fish?
AB  - A Ser48 phospholipase A2-homologue, ammodytin L, which is myotoxic in mammals and
      devoid of any phospholipase A2 activity, completely inhibits the specific binding
      of the neurotoxic phospholipase A2, ammodytoxin C, to fish presynaptic membranes
      from Torpedo marmorata electric organ. In cross-linking experiments, 125I
      ammodytin L labels the same membrane proteins as 125I-ammodytoxin C (70, 38.5
      57.4 and 19.7 kDa). The formation of these adducts is completely prevented by the
      presence of ammodytoxin C but not of a non-toxic phospholipase A2, ammodytin I2.
      A chimeric phospholipase A2, constructed by associating the N-terminal half of
      ammodytoxin to the C-terminal half of ammodytin L, possesses a low, but
      significant phospholipase A2 activity, however it is not toxic to mice, probably
      due to abolition of the specific neuronal acceptor binding in mammals.
      Nevertheless, the chimeric phospholipase A2 is able to interact with the
      ammodytoxin acceptor in Torpedo marmorata electric organ. The existence of
      neuronal acceptors for ammodytin L and for the chimeric phospholipase A2 suggests
      that they may act as neurotoxins in fish. As ammodytin L does not possess any
      enzymatic activity it, therefore, appears to be an excellent tool to investigate
      the mechanism of action of beta-neurotoxins independently of their phospholipase
      A2 activity.

PMID- 9514951
TI  - A new prenylated flavone from Artocarpus champeden inhibits the K(+)-dependent
      amino acid transport in Bombyx mori midgut.
AB  - The effect of some flavonoids on the K(+)-dependent and K(+)-independent leucine
      uptake into brush border membrane vesicles from Bombyx mori larval midgut was
      investigated. Among the compounds tested, cyclochampedol, recently purified from
      Artocarpus champeden, was able to inhibit in micromolar range the leucine
      transport. The inhibition occurred both in the absence and in the presence of
      potassium and was not affected by leucine concentration. The apparent Ki was 0.25
      mM. Cyclochampedol represents the first non-competitive inhibitor of an amino
      acid transport system in Lepidoptera. The relevance of this result is discussed.

PMID- 9514952
TI  - Transcriptional regulation of pre-pro-endothelin-1 gene by glucocorticoids in
      vascular smooth muscle cells.
AB  - Endothelin is a potent vasoactive peptide involved in the maintenance of vascular
      tone and in pathophysiological states. Endothelin-1 synthesis is controlled at
      the transcriptional level. We report that glucocorticoids increase the pre-pro
      endothelin-1 gene transcription rate in vascular smooth muscle cells. The effect
      of glucocorticoids is dose-dependent (EC50 approximately 2-3 nM) and completely
      blocked by co-incubation with the glucocorticoid antagonist RU 38486. The rise in
      pp-Et-1 steady state mRNA levels is rapid and transient with a maximal three-fold
      stimulation within one hour of glucocorticoid administration. Glucocorticoid
      treatment does not affect the half-life of pre-pro-endothelin-1 mRNA as shown by
      actinomycin D studies. Furthermore, cycloheximide treatment concomitantly with RU
      28362 did not reverse the stimulatory effect of glucocorticoids on pre-pro
      endothelin-1 mRNA levels. Nuclear run-on analysis shows that glucocorticoids
      increase the transcription rate of pre-pro-endothelin-1. Our results suggest a
      role for glucocorticoids in the regulation of biosynthesis and action of this
      important vasoactive peptide in vascular smooth muscle cells.

PMID- 9514953
TI  - Functional analysis of conserved histidines in ADP-glucose pyrophosphorylase from
      Escherichia coli.
AB  - Two absolutely conserved histidines and a third highly conserved histidine are
      noted in 11 bacterial and plant ADP-glucose pyrophosphorylases. These histidines
      were individually mutagenized in the E. coli enzyme to glutamine in order to
      determine their function. Glutamine mutations at residues 143 and 156 produced
      functional enzymes in cell extracts with slightly lower than wild-type specific
      catalytic activities and with same heat stability characteristics of the wild
      type enzyme. Substitution of residue 83 with glutamine however produced an enzyme
      having decreased thermal stability. Additional mutageneses at residue 83 with
      asparagine, arginine, or aspartate gave rise to enzymes having a progressively
      decreasing trend in thermal stability. These mutants are more susceptible to
      proteolysis than wild-type enzyme. Kinetic analysis of H83Q and H83N indicates
      that histidine 83 is not involved in the catalytic mechanism or in substrate
      binding but possibly in maintenance of the active catalytic structure.

PMID- 9514954
TI  - Adherence to endothelial cells induces release of soluble tumor necrosis factor
      (TNF) receptor forms from neutrophil granulocytes.
AB  - The TNF receptors, TNF-R55 and TNF-R75, may undergo proteolytic cleavage and form
      soluble receptor forms, TNF-R55-BP and TNF-R75-BP. Neutrophils are abundant with
      both forms of TNF-receptors, while endothelial cells (ECV 304) only express TNF
      R55. Human neutrophils were allowed to interact with an unstimulated or a IL-1
      beta stimulated endothelium followed by determination of TNF-R75-BP with ELISA.
      Neutrophils in suspension or in contact with an unstimulated endothelium released
      only low amounts of TNF-R75-BP. However, neutrophils released significant amounts
      of TNF-R75-BP after adherence to an endothelium stimulated with IL-1 beta.
      Neutrophils were not generally activated during adherence since concomitant
      release of lactoferrin from neutrophils only reached levels of 1-5% compared with
      incubation with phorbolesters. Blocking integrins with antibodies to CD11/CD18
      resulted in inhibition of both neutrophil adherence to an endothelium and
      shedding of TNF-R75. In addition, TNF-R55-BP decreased the production of TNF from
      IL-1 beta stimulated endothelial cells, suggesting that soluble TNF receptor
      forms are able to inhibit TNF production.

PMID- 9514955
TI  - Selective expression of beta 7 integrin on lymphocytes undergoing apoptosis in
      lymphoid tissues.
AB  - It has been previously shown that the beta 7 chain of integrin forms heterodimers
      with the alpha 4 or alpha E chain, which plays essential roles in lymphocyte
      homing to mucosal lymphoid tissues. The aim of this study was to re-evaluate the
      possible role of the beta 7 integrin other than lymphocyte homing. We prepared
      spleen and lymph node lymphocytes from biopsied specimens from macaque monkeys
      and examined for the reactivity with a monoclonal antibody specific for the beta
      7 chain. As a result, a minor population of the lymphocytes with a smaller size,
      which were in the early stage of apoptosis, was found to express a higher level
      of the beta 7 integrin than a majority of the lymphocytes with a normal size.
      Interestingly, the apoptotic lymphocytes expressed neither alpha 4 nor alpha E
      chains, suggesting that the beta 7 chain on these cells may be associated with an
      undefined alpha chain. These findings indicate that in the lymphoid tissues the
      shrunken lymphocytes undergoing apoptosis selectively express a unique beta 7
      integrin.

PMID- 9514956
TI  - The intermediate form of glycine-extended adrenomedullin is the major circulating
      molecular form in human plasma.
AB  - Adrenomedullin (AM), a potent vasodilator peptide, is processed from its AM
      precursor as glycine-extended AM (AM-gly), an intermediate form of AM.
      Subsequently, mature AM is converted from AM-gly by enzymatic amidation. Using
      two kinds of radioimmunoassay which recognize the entire AM molecule (E-AM-RIA)
      and C-terminal amide structure (C-AM-RIA), human plasma AM immunoreactivity was
      chromatographically characterized. In analyses of gel filtration and reverse
      phase high-performance liquid chromatography, most of the AM immunoreactivity
      measured by E-AM-RIA was eluted at a position identical to where mature AM and AM
      gly emerged and was not recognized by C-AM-RIA. These data show that
      immunoreactive AM measured by E-AM-RIA is not amidated. When amidated by
      peptidylglycine alpha-amidating enzyme, the immunoreactive AM was converted to a
      form that can be detected by C-AM-RIA. These results indicate that most of the
      total AM immunoreactivity measured by E-AM-RIA represents immunoreactivity of AM
      gly and that the concentration of immunoreactive mature AM in plasma is much
      lower than that of AM-gly. In practice, plasma concentration of AM-gly and mature
      AM in healthy volunteers was 2.7 +/- 0.18 fmol/ml and 0.48 +/- 0.05 fmol/ml,
      respectively. Furthermore, plasma concentration of AM-gly and total AM was
      significantly elevated in patients with hypertension compared to normotensive
      control. The present data indicate that most of circulating plasma AM
      immunoreactivity is occupied by AM-gly, an intermediate form of AM, which may
      reflect the process of production of AM in tissues.

PMID- 9514958
TI  - An aspartic acid residue near the second transmembrane segment of ATP
      receptor/channel regulates agonist sensitivity.
AB  - Charged or polarized amino acid residues near or within the second transmembrane
      (M2) segment of neuronal ATP receptor/channels (P2X2 receptors) were neutralized
      by site-directed mutagenesis, and the properties of the mutants were
      electrophysiologically characterized using Xenopus oocytes. When Asp315 was
      substituted with Val (D315V), the sensitivity to ATP was reduced by about 60
      fold. The sensitivity to ATP was not affected by the neutralization of Lys324,
      which is involved in a Walker type A ATP-binding sequence, Lys366, Tyr330, or
      Asn333. With D315V channels, the sensitivities to other agonists (ADP, ATP gamma
      S, and 2-methylthio ATP) were also reduced. The sensitivities to antagonists
      (suramin and Cibacron Blue F3GA) were, however, not affected by this
      neutralization. The results suggest that Asp315, which is assumed to be present
      in the extracellular region near the M2 segment of P2X2 receptor/channels, serves
      to maintain agonist sensitivity.

PMID- 9514959
TI  - Volume 217, Number 2 (1996), in Article No. 0152 "Cellular Proteins That Bind to
      the Hepatitis B Virus Posttranscriptional Regulatory Element," by Zhi-Ming Huang,
      Wei-Qing Zang, and T. S. Benedict Yen, pages 573-581
AB  - Copyright

PMID- 9514957
TI  - Cloning and characterization of the 5'-flanking region of the human cardiotrophin
      1 gene.
AB  - To enable the analysis of the regulation of the human cardiotrophin-1 gene
      expression, the 5'-flanking region of the human cardiotrophin-1 gene was cloned
      and sequenced. Data bank search revealed several cis- active DNA elements (SP1,
      CREB, C/EBP, AP1 and AP-2 like and GATA) in the proximal 1.1 kb region. Six
      nested 5-'terminal deletion mutants from -1091/+39 to -218/+39 were fused to a
      luciferase reportergene and proved to be functionally active after transfection
      into COS-7 cells.

PMID- 9514960
TI  - Assembly of viroplasm and virus-like particles of rotavirus by a Semliki Forest
      virus replicon.
AB  - In this study we have used an expression system based on Semliki Forest virus
      (SFV) to study assembly and intracellular localization of certain capsid proteins
      of rotavirus in neurons and mammalian epithelial cells. The complete genes of vp2
      (vp2A) and vp6 (vp6A) of group A rotavirus (SA-11) and gene 5 encoding vp6 (vp6C)
      of porcine group C rotavirus (strain Cowden/AmC-1) were inserted into an SFV
      expression replicon. Transfection of BHK-21 cells with in vitro-made SFV
      transcripts resulted in a high level of expression of the heterologous genes.
      Cotransfection with helper RNA encoding the SFV structural proteins, but lacking
      the genomic RNA packing signal, resulted in production of recombinant infectious
      virus. Immunological and biochemical analysis revealed that vp6 was expressed to
      high levels in primary neurons and mammalian epithelial cells and that vp6 was
      retained as an authentic homotrimer, stabilized by noncovalent interactions with
      native antigenic determinants. Thin section electron microscopy analysis revealed
      that vp6 alone assembled into viroplasm-like structures in the cytoplasm. While
      coexpression of vp2 and vp6 of group A rotavirus resulted in formation of single
      shelled-like particles, no evidence of intracellular assembly was found,
      suggesting that other viral proteins are required for intracellular formation of
      single-shelled particles. A notable observation was that the vp6 proteins of
      group A and C rotaviruses showed different immunofluorescence patterns in BHK-21
      cells; vp6C displayed an intense punctate immunofluorescence pattern, while vp6A
      was characterized by a pronounced filamentous staining in close vicinity to the
      cytoskeleton.

PMID- 9514961
TI  - Mapping regions of the cauliflower mosaic virus ORF III product required for
      infectivity.
AB  - The open reading frame (ORF) III product (PIII) of the pararetrovirus cauliflower
      mosaic virus (CaMV) has nucleic acid-binding properties in vitro, but its
      biological role is not yet determined. ORF III is closely linked to ORF II and
      overlaps ORF IV out of frame in the CaMV genome. A new CaMV-derived vector (Ca
      delta) devoid of ORF III and containing unique restriction sites between ORFs II
      and IV was designed. Introduction of the wild-type CaMV ORF III into Ca delta
      results in a clone (Ca3) infectious in turnip plants. Truncated or point-mutated
      versions of ORF III were then inserted into Ca delta and tested in vivo.
      Inoculation of the different mutants into turnip revealed that the four C
      terminal amino acid residues of PIII are dispensable for infectivity as well as
      an internal domain (amino acids 61 to 80). Taken together the results show that
      PIII possesses a functional two-domain organization. Moreover, the CaMV PIII
      function(s) cannot be replaced either by the PIII protein of another
      caulimovirus, the figwort mosaic virus, or by the P2 protein of the cacao swollen
      shoot badnavirus, a member of the second plant pararetrovirus group.

PMID- 9514962
TI  - Nucleolar localization of mouse mammary tumor virus proteins in T-cell lymphomas.
AB  - To characterize novel proteins expressed in lymphoma cells, monoclonal antibodies
      (MAbs) were raised against variant S49 mouse lymphoma cells. Immunoperoxidase
      analysis with a specific MAb, named M-66, revealed nuclear localization with
      prominent staining in the nucleoli of both tumorigenic (T-63) cells and
      nontumorigenic, immunogenic (T-25-Adh) cells. Weak signals were also observed in
      the cytoplasm and plasma membrane of both cells. Western blot analysis with M-66
      antibody revealed a 14-kDa protein in nuclear extracts of both T-25-Adh and T-63
      cells. An additional nuclear 21-kDa protein was evident only in T-63 cells. M-66
      identified several clones from a T-25-Adh cDNA expression library. These clones
      demonstrated extensive homology (approximately 95% identity throughout their
      length) to the mouse mammary tumor virus (MMTV) env and LTR regions. Extensive
      amino acid sequence homology (approximately 90% identity) between the clones and
      the env protein was observed. M-66 identified the 14-kDa protein in another MMTV
      bearing T-cell lymphoma, EL-4. Immunoperoxidase analysis of EL-4 cells with M-66
      also revealed prominent nucleolar staining. MMTV-negative cells and MMTV-positive
      cells of nonlymphocytic origin were devoid of both 14- and 21-kDa proteins.
      Moreover, an anti-MMTV gp52 (env) antibody precipitated the 21-kDa protein in T
      63 cells. We thus suggest that MMTV bearing T-cell lymphomas express nucleolar
      proteins translated from the env region of MMTV.

PMID- 9514963
TI  - Suppression of rat bone marrow cells by Friend murine leukemia virus envelope
      proteins.
AB  - In a retroviral rat model, we have investigated the nontransforming effects of
      murine leukemia virus FB29 on the bone marrow. Upon intraperitoneal inoculation
      with murine leukemia virus FB29 of either neonatal or adult rats, bone marrow
      cells became massively infected within the first 12 days postinoculation. In
      neonatally inoculated rats, a persistent productive bone marrow infection was
      established, whereas in rats inoculated as adults, no infected bone marrow cells
      could be detected beyond 12 days postinoculation. Retroviral infection was most
      likely cleared by an antiviral immune response (Hein et al., 1995, Virology 211,
      408-417). Exposure to virus irreversibly decreased numbers of bone marrow cells
      staining with monoclonal antibody OX7 by 10-30%. Reduction of OX7+ bone marrow
      cells by 20% was also observed in vitro, after bone marrow cells from uninfected
      adult rats had been co-incubated with virus. FB29-envelope proteins were
      sufficient alone to reduce numbers of OX7+ bone marrow cells, both in vivo and in
      vitro. According to results on incorporation of propidium iodide, decreased
      numbers of OX7+ cells were due to cell death. By flow cytometric analyses OX7+
      bone marrow cells as well as monocytes/macrophages were identified to be major
      target cells for infection with FB29 within the bone marrow. Thus, the
      mechanism(s) responsible for death of OX7+ bone marrow cells might be due to
      direct toxicity of viral envelope proteins and/or to interactions of viral
      envelope proteins with cells of the monocytic lineage.

PMID- 9514964
TI  - Characterization of the brome mosaic virus movement protein expressed in E. coli.
AB  - The biochemical and functional properties of the movement protein (MP) of brome
      mosaic virus (BMV) were investigated. Expression and purification of the BMV MP
      from Escherichia coli resulted in a pure and soluble protein preparation. Sucrose
      gradient centrifugation revealed that BMV MP forms oligomers consisting of two or
      more copies but no higher order multimers even when different ionic strengths and
      pHs were applied. Nitro-cellulose filter binding and gel retardation studies
      showed that in vitro the BMV MP preferentially bound to ss nucleic acids (RNA and
      DNA); the affinity to ssRNA was lower compared to BMV coat protein. The binding
      to ss nucleic acid was cooperative and not sequence specific and the hypothetical
      binding site was calculated to be around three to six nucleotides per MP monomer.
      The nucleic acid binding properties of the BMV MP are discussed in relation to
      the recent finding that this protein is also able to form tubular structures in
      infected protoplasts.

PMID- 9514965
TI  - The host range and interference properties of two closely related feline leukemia
      variants suggest that they use distinct receptors.
AB  - The proviral clones 61E and 61C represent two closely related variants of feline
      leukemia virus (FeLV) that exhibit significant differences in their biological
      and pathogenic properties. The major pathogenic determinant has been mapped to
      the extracellular envelope glycoprotein (Env-SU), but the mechanism by which
      envelope differences influence pathogenesis is not well understood. Moreover, it
      is unclear whether these viruses infect the same target cells and/or enter cells
      using the same receptor. In the present study, we exploited a recently developed
      single cycle infection assay to examine the host range and interference
      properties of 61E and 61C FeLVs and found that these two FeLV variants differ
      significantly in their host ranges and receptor usages. FeLV-61C was found to be
      an ecotropic virus; the entry of viruses bearing a 61C envelope protein (Env-SU)
      into cell lines was limited to feline T-cells and feline fibroblasts. In
      contrast, the host range of 61E includes, in addition to all feline cells
      examined, some canine, murine, and human cell lines. Feline fibroblast and feline
      T-cells that expressed 61E envelope were resistant to infection with a virus
      bearing a 61E Env-SU, whereas these same cells were susceptible to infection by
      an otherwise similar virus pseudotyped with the 61C Env-SU. This pattern of
      interference was observed in cells expressing 61E envelope alone, in the absence
      of other FeLV gene products, demonstrating that interference was mediated
      specifically by Env-SU. Fibroblast cells chronically infected with a 61C virus
      were partially resistant to infection with a virus having a 61C Env-SU, but were
      not resistant to infection by a virus having a 61E Env-SU. On the basis of the
      current understanding of virus-receptor interactions, the lack of interference
      between 61E and 61C under conditions where there is significant homologous
      interference, combined with the differences in their host cell range, leads us to
      conclude that 61E and 61C use two distinct primary cellular receptors for entry.

PMID- 9514966
TI  - Molecular epidemiology of HTLV-II among United States blood donors and
      intravenous drug users: an age-cohort effect for HTLV-II RFLP type aO.
AB  - Molecular subtyping was used to investigate the epidemiology of human T
      lymphotropic virus type II (HTLV-II) in the United States. Nested polymerase
      chain reaction of the HTLV-II long terminal repeat region followed by restriction
      fragment length polymorphism (RFLP) analysis was performed on HTLV-II
      seropositive subjects including 97 U.S. blood donors without major risk factors
      for HTLV-II infection, 53 injection drug users (IDU), and 10 American Indian
      blood donors. Three new HTLV-II RFLP types were confirmed with DNA sequencing and
      phylogenetic analysis. HTLV-II RFLP type aO (Switzer classification) was
      associated with older age [adjusted odds ratio (OR) 1.06 per year of age, 95%
      confidence interval (CI) 1.02-1.09] and with Black (OR 5.24, 95% CI 1.90-14.47)
      and White (OR 4.43, 95% CI 1.67-11.75) race/ethnicity. These data are consistent
      with an age-cohort effect for HTLV-II RFLP type aO among older White and Black
      IDU and blood donors. This finding could be explained by an epidemic of non-aO
      HTLV-II RFLP types among younger persons of Hispanic and other race/ethnicity,
      superimposed upon endemic HTLV-II RFLP type aO among older Black and White
      persons.

PMID- 9514967
TI  - Processing of the coronavirus MHV-JHM polymerase polyprotein: identification of
      precursors and proteolytic products spanning 400 kilodaltons of ORF1a.
AB  - The replicase of mouse hepatitis virus strain JHM (MHV-JHM) is encoded by two
      overlapping open reading frames, ORF1a and ORF1b, which are translated to produce
      a 750-kDa precursor polyprotein. The polyprotein is proposed to be processed by
      viral proteinases to generate the functional replicase complex. To date, only the
      MHV-JHM amino-terminal proteins p28 and p72, which is processed to p65, have been
      identified. To further elucidate the biogenesis of the MHV-JHM replicase, we
      cloned and expressed five regions of ORF1a in bacteria and prepared rabbit
      antisera to each region. Using the immune sera to immunoprecipitate radiolabeled
      proteins from MHV-JHM infected cells, we determined that the MHV-JHM ORF1a is
      initially processed to generate p28, p72, p250, and p150. Pulse-chase analysis
      revealed that these intermediates are further processed to generate p65, p210,
      p40, p27, the MHV 3C-like proteinase, and p15. A putative replicase complex
      consisting of p250, p210, p40, p150, and a large protein (> 300 kDa)
      coprecipitate from infected cells disrupted with NP-40, indicating that these
      proteins are closely associated even after initial proteolytic processing.
      Immunofluorescence studies revealed punctate labeling of ORF1a proteins in the
      perinuclear region of infected cells, consistent with a membrane-association of
      the replicase complex. Furthermore, in vitro transcription/translation studies of
      the MHV-JHM 3Cpro and flanking hydrophobic domains confirm that 3C protease
      activity is significantly enhanced in the presence of canine microsomal
      membranes. Overall, our results demonstrate that the MHV-JHM ORF1a polyprotein:
      (1) is processed into more than 10 protein intermediates and products, (2)
      requires membranes for efficient biogenesis, and (3) is detected in discrete
      membranous regions in the cytoplasm of infected cells.

PMID- 9514968
TI  - Multiple cis elements contribute to geminivirus origin function.
AB  - The genome of the geminivirus tomato golden mosaic virus (TGMV) consists of two
      circular DNA molecules which are dissimilar in sequence except for a highly
      conserved 200-bp common region that includes the origin for rolling circle
      replication. To better characterize the plus-strand origin, we analyzed the
      capacities of various TGMV common region sequences to support episomal
      replication in tobacco protoplasts when the viral replication proteins AL1 and
      AL3 were supplied in trans. These experiments demonstrated that the minimal
      origin is located in 89-bp common region fragment that includes the known AL1
      binding motif and a hairpin structure containing the DNA cleavage site. Analyses
      of mutant origin sequences identified two additional cis elements--one that is
      required for origin activity and a second that greatly enhances replication. In
      contrast, a conserved partial copy of the AL1 binding site did not contribute to
      origin function. Mutational analysis of the functional AL1 binding site showed
      that both spacing and sequence of this motif are important for replication in
      vivo and AL1/DNA binding in vitro. Spacing changes between the AL1 binding site
      and hairpin also negatively impacted TGMV origin function in a position-dependent
      manner. Together, these results demonstrated that the organization of TGMV plus
      strand origin is complex, involving multiple cis elements that are likely to
      interact with each other during initiation of replication.

PMID- 9514969
TI  - The neutralization epitope of lactate dehydrogenase-elevating virus is located on
      the short ectodomain of the primary envelope glycoprotein.
AB  - We have measured by indirect ELISA the binding of neutralizing and non
      neutralizing anti-lactate dehydrogenase-elevating virus (LDV) polyclonal and
      monoclonal antibodies to synthetic peptides representing unmodified hydrophilic
      segments of LDV proteins. Using this method a single neutralization epitope has
      been shown to be located in the very short (about 30 amino acid long) ectodomain
      of the primary envelope glycoprotein, VP-3P, encoded by ORF 5. Although the
      neutralization epitopes of neuropathogenic and non-neuropathogenic LDVs differ
      slightly in amino acid sequences, the neutralizing antibodies bind strongly to
      the epitopes of both groups of viruses. However, the neutralization epitopes of
      neuropathogenic and non-neuropathogenic LDVs are associated with different
      numbers of polylactosaminoglycan chains (1 and 3, respectively) which may affect
      the binding of neutralizing antibodies to the virions of these LDVs. The ELISA
      using synthetic peptides containing the neutralization epitope provides a novel,
      rapid, sensitive, and inexpensive method for quantitating LDV neutralizing
      antibodies in infected mice.

PMID- 9514970
TI  - Intracellular retention of duck hepatitis B virus large surface protein is
      independent of preS topology.
AB  - The mechanism of intracellular retention for the large surface protein (L) of
      duck hepatitis B virus (DHBV) was analyzed by examination of the transmembrane
      topologies and secretory properties of a collection of DHBV L mutants and
      compared with that of human hepatitis B virus (HBV) L. Our results demonstrate
      that, in contrast to its HBV counterpart, intracellular retention of DHBV L does
      not depend on the cytosolic disposition of its preS domain. L mutants with either
      cytosolic or lumenal preS were mostly retained in the absence of the small
      surface protein (S), whereas coexpression with S resulted in efficient secretion
      of both topological forms. Coexpression of the wild-type DHBV L with S resulted
      in efficient incorporation of L into secreted S + L particles, whereas HBV L was
      partially excluded from secreted particles under the same conditions. We propose
      that HBV provides L retention even in the presence of an excess of S, by
      exclusion of molecules with cytosolic preS domains from secreted particles at the
      stage of their assembly. DHBV lacks such a retention mechanism due to the absence
      of topological selection in particulate assembly.

PMID- 9514971
TI  - Role of gp41 glycosylation sites in the biological activity of human
      immunodeficiency virus type 1 envelope glycoprotein.
AB  - The requirement for glycosylation in the transmembrane protein, gp41, of human
      immunodeficiency virus type 1 envelope protein for fusion activity has been
      studied. By using a mutant gene in which three conserved sites have been removed
      and which shows no fusion ability, genes were constructed which replace one, two,
      or three sites in all possible combinations. Following expression of the
      resultant proteins using the vaccinia T7 system, each Env variant was assessed by
      visual and quantitative syncytium assays. Our data indicate that two sites are
      sufficient for high levels of fusion and that the single site at position 621 is
      the most critical of all positions. We interpret our data in the light of
      previous contradictory reports on the role of gp41 glycosylation in bioactivity
      and the emerging structure of gp41.

PMID- 9514972
TI  - Characterization of the small subunit of the terminase enzyme of the Bacillus
      subtilis bacteriophage SPP1.
AB  - The small subunit of bacteriophages SPP1 and SF6 terminase, G1P, share 71%
      identity clustered in three conserved segments (I, II, and III). Within segment I
      the helix-turn-helix DNA-binding domain was mapped, whereas segment III was found
      to be nonessential. For terminase activity, chimeric G1Ps, obtained by domain
      swapping between gene 1 of SPP1 and the SF6 origin (Chi1 to Chi4), were purified.
      The chimeric proteins behave in all respects similarly to the G1P of SPP1 or SF6.
      The major determinant for G1P:G1P interactions was found to lie within segment
      II. We showed that a G1P derivative (G1P*) lacking the 62 N-terminal residues
      (segment I), and Chi1 lacking the 45 C-terminal residues (segment III) interact
      with G1P. The N-terminal domain of G1P is necessary for terminase subunit
      assembly, because the large subunit of the terminase (G2P) interacts only with
      G1P and Chi1, but fails to do so with G1P*. These results suggest that segment
      III and the extended C-terminal part of SPP1 G1P do not play a major role in DNA
      recognition and that G1P recognizes an extended nucleotide sequence and DNA
      structure.

PMID- 9514973
TI  - A vibriophage, KVP40, with major capsid protein homologous to gp23* of coliphage
      T4.
AB  - The mcp gene encoding the major capsid protein (Mcp) of vibriophage KVP40, a
      large-tailed DNA phage, was cloned and sequenced. The nucleotide sequence of the
      mcp gene was 64.4% similar to that of gene 23 of coliphage T4. Analysis of the N
      terminal amino acid sequence of purified native Mcp revealed that the mcp gene
      actually coded for a precursor, pro-Mcp, whose 62 N-terminal amino acids must be
      removed upon maturation to Mcp. Thus, mature Mcp would consist of 452 amino acid
      residues and have a calculated molecular mass of 47,561 Da. Comparison of amino
      acid sequences of Mcp and gp23*, the major capsid protein of T4, demonstrated
      61.8% identity and 89.7% similarity between them. In addition, a sequence,
      TATAAATA, identical to a typical T4 late promoter sequence was seen in the region
      upstream of the mcp gene. These findings, together with their morphological
      similarity, suggest that KVP40 and T4 are phylogenetically related.

PMID- 9514974
TI  - The human papillomavirus type 18 (HPV18) replication protein E1 is a
      transcriptional activator when interacting with HPV18 E2.
AB  - The human papillomavirus type 18 E1 and E2 proteins are both required for the
      initiation of viral DNA replication. Whereas E2 is the major viral transcription
      regulator, E1 is the replication initiator protein. They interact with each other
      and with the origin sequences to initiate viral DNA replication. We show that the
      HPV18 E1 and E2 proteins, when bound to an origin sequence cloned upstream of a
      heterologous promoter, synergistically activate transcription. This synergy
      required binding of E2 to at least two binding sites, but was partially
      independent of E1 binding to the origin of replication. Transcriptional
      activation was observed even in the absence of replication of the target DNA.
      Only homologous E1 and E2 proteins binding to homologous origin sequences from
      BPV1 or HPV18 viruses could synergistically activate transcription. We show that
      the HPV18 E1 protein can activate transcription when targeted to the DNA by
      fusion of the complete polypeptide with the BPV1 E2 C-terminus dimerization/DNA
      binding domain, implying that HPV18 E1 is an intrinsic transcriptional activator,
      though less potent than E2. The interaction between E1 and E2 may form a
      transcriptionally active complex during initiation of viral DNA replication.

PMID- 9514975
TI  - Topoisomerase I stimulates SV40 T antigen-mediated DNA replication and inhibits T
      antigen's ability to unwind DNA at nonorigin sites.
AB  - We have previously found that purified SV40 T antigen and topoisomerase I (topo
      I) bind to one another in vitro. In this report, we determined the effects of
      human topo I on T antigen-mediated DNA replication and investigated whether it
      altered T antigen's biochemical activities. Topo I stimulates DNA replication and
      especially increases the amounts of finished circular molecules. This protein had
      no effect on T antigen's ability to bind, distort, or unwind the origin of
      replication. However, unwinding of DNA by T antigen was strongly inhibited by
      topo I when it was initiated at sites other than the origin. We demonstrate that
      the presence of T antigen binding sites in DNA interfere with inhibition of
      unwinding by topo I. These results indicate that topo I may increase the
      specificity of unwinding by inhibiting the reaction at non-origin sites.
      Fragments of T antigen that bind to topo I abrogate topo I's inhibition of non
      origin-dependent unwinding, indicating that topo I inhibits unwinding through a
      direct interaction with T antigen. We propose a model whereby T antigen and topo
      I function together at the origin to specifically unwind it and initiate DNA
      replication.

PMID- 9514976
TI  - Intracellular location of two groundnut rosette umbravirus proteins delivered by
      PVX and TMV vectors.
AB  - The proteins encoded by open reading frames (ORF) 3 and 4 of groundnut rosette
      umbravirus (GRV) were expressed in Nicotiana benthamiana as fusions with green
      fluorescent protein (GFP) from modified potato virus X (PVX) and tobacco mosaic
      virus (TMV) vectors. Regardless of which plant virus vector was used, GFP fused
      to the ORF3 protein accumulated in large cytoplasmic inclusion bodies and in
      nucleoli, whereas GFP fused to the ORF4 protein was found in cell walls close to
      plasmodesmata. Cell-to-cell movement of PVX requires three proteins encoded by
      the triple gene block (TGB) and also the coat protein (CP). However, when GRV
      ORF4 was substituted for the PVX CP gene, the hybrid virus was able to move
      normally in inoculated leaves but not into noninoculated leaves. In contrast,
      when GRV ORF4 was substituted for the TGB, or for both the TGB and the CP gene,
      movement of the hybrid viruses was limited to a few epidermal cells neighboring
      the infection site. Thus, the GRV ORF4 protein can replace the movement proteins
      of PVX for some of their functions.

PMID- 9514977
TI  - Sendai viruses with altered P, V, and W protein expression.
AB  - Wild-type Sendai virus expresses three proteins containing the N-terminal half of
      the P protein open reading frame due to mRNA editing; a full-length P protein
      (ca. 70% of the total), a V protein with the N-terminal half fused to a Cys-rich
      Zn(2+)-binding domain (ca. 25% of the total), and a W protein representing the N
      terminal half alone (ca. 5% of the total). To examine the role of these proteins
      in the virus life cycle, we have prepared recombinant viruses in which the normal
      V mRNA expresses a W protein (V-stop; 70% P, 30% W), one which cannot edit its P
      gene mRNA (delta 6A; 100% P), and one which overedits its mRNA like parainfluenza
      virus type 3 (swap/8;20-40% P, 30% V, 30% W). All these viruses were readily
      recovered and grew to similar titers in eggs, and except for the P gene products,
      cell lines individually infected with these viruses accumulated similar amounts
      of viral macromolecules. The relative competitive advantage of each virus was
      determined by multiple cycle coinfections of eggs and found to be rSeV-Vstop =
      rSeV-wt >> rSeV-delta 6A > rSeV-swap/8. On the other hand, rSeV-swap/8 underwent
      multiple cycles of replication in C57BI/6 mouse lungs and was highly virulent for
      these animals, whereas rSeV-delta 6A was avirulent in mice and this infection was
      quickly cleared. Remarkably, rSeV-Vstop appeared to be more virulent for inbred
      C57BI/6 mice than rSeV-wt, but was partially attenuated in infections of outbred
      ICR mice. Thus, the expression of either the V or the W proteins is sufficient
      for multiple cycles of infection and pathogenesis in C57BI/6 mice, whereas W can
      only partially substitute for V for pathogenesis in ICR mice.

PMID- 9514978
TI  - Arginine residues in the C-terminus of HIV-1 Vpr are important for nuclear
      localization and cell cycle arrest.
AB  - HIV-1 viral protein R (Vpr) is predominantly localized to the nucleus and plays
      an important role for viral preintegration complex import into the nucleus. In
      this study, we investigated the influence on subcellular localization of Arg
      residues in the C-terminus of Vpr. Consistent with previous studies, about 90% of
      the cells manifested diffuse nuclear staining in the Vpr-expressed cells. Besides
      diffuse nuclear staining, punctate perinuclear staining, and punctate cytoplasmic
      staining were also observed in the immunofluorescence studies. Deletion of the
      Ser-Arg-lle-Gly residues (amino acids 79-82; SRIG) had no effect on the Vpr
      localization. However, deletion of the Arg-Gln-Arg-Arg residues (amino acids 85
      88; RQRR) resulted in a smooth perinuclear staining pattern. Substitution of five
      Arg residues with Asn (amino acids 80, 85, 87, 88, and 90; R-->N5) resulted in a
      diffuse cytoplasmic staining. Subcellular fractionation analyses support the
      immunofluorescence staining results. These findings indicate that the C-terminal
      Arg residues of HIV-1 Vpr play an important role for Vpr nuclear localization.
      All the Vpr mutants were appropriately expressed, exhibited no significant defect
      on the protein stability, and were incorporated efficiently into virus-like
      particles. Both SRIG and R-->N5 mutants lost their cell cycle arrest activities
      and the RQRR deletion only exhibited a low level of cell arrest activity.
      Therefore, the Arg residues in the HIV-1 Vpr C-terminus are important for Vpr
      nuclear localization and cell cycle arrest, but had no effect on protein
      stability or Vpr incorporation into virus-like particles.

PMID- 9514979
TI  - Group I introns found in Chlorella viruses: biological implications.
AB  - More than 80 group I introns were detected and characterized in Chlorella viruses
      isolated from various locations in Japan; the overall average frequency of
      viruses containing the group I intron was 8.0%. Although most of these introns
      were inserted in the gene for either transcriptional elongation factor TFIIS
      (approximately 60%) or URF 14.2 (unidentified open reading frame coding for a
      14.2-kDa polypeptide) (approximately 40%), in a few cases, the gene for the major
      capsid protein Vp52 contained an intron. These introns were biologically active
      (self-splicing) both in vivo and in vitro. Viruses that contained introns almost
      usually contained only one, but more than two introns coexisted in several virus
      isolates. Nucleotide sequence analysis showed that the intron sequences have
      diverged under strong constraint of the exon genes: introns in the same gene
      showed more than 99% sequence identity, whereas introns in different genes were
      only 72-78% identical. Phylogenetic analysis suggested relatedness of these
      introns to those found in the rRNA genes of a variety of organisms including
      green algae, red algae, red algae, yeasts, fungi, and protozoa.

PMID- 9514980
TI  - Nonlinear ribosome migration on cauliflower mosaic virus 35S RNA in transgenic
      tobacco plants.
AB  - Cauliflower mosaic virus (CaMV) uses a specialised translation mechanism to
      bypass the long leader sequence of the 35S RNA. The effect of the CaMV 35S RNA
      leader sequence on the expression of a downstream beta-glucuronidase (GUS)
      reporter gene was studied in transgenic tobacco plants. Enzymatic GUS assays of
      these transgenic plants show that a shunt mechanism of translation indeed occurs
      in planta with an average efficiency of 5% compared with the leaderless
      construct. Histological GUS analyses indicate that the shunt mechanism occurs
      throughout the whole plant and at all developmental stages.

PMID- 9514981
TI  - Learning to knock out male infertility.

PMID- 9514982
TI  - Super sponges.

PMID- 9514983
TI  - Messenger of safety.

PMID- 9514984
TI  - Cellular and molecular basis of beta-amyloid precursor protein metabolism.
AB  - In molecular neurobiology, perhaps no molecule has been as thoroughly examined as
      Alzheimer's beta-amyloid precursor protein (betaAPP). In the ten years since the
      cDNA encoding betaAPP was cloned, the protein has been the subject of
      unparalleled scrutiny on all levels. From molecular genetics and cellular biology
      to neuroanatomy and epidemiology, no scientific discipline has been left
      unexplored - and with good reason. beta-amyloid (Abeta) is the main constituent
      of the amyloidogenic plaques which are a primary pathological hallmark of
      Alzheimer's disease, and betaAPP is the protein from which Abeta is cleaved and
      released. Unraveling the molecular events underlying Abeta generation has been,
      and remains, of paramount importance to scientists in our field. In this review
      we will trace the progress that has been made in understanding the molecular and
      cellular basis of betaAPP trafficking and processing, or alternatively stated,
      the molecular basis for Abeta generation. Imperative to a complete understanding
      of Abeta generation is the delineation of its subcellular localization and the
      identification of proteins which play either direct or accessory roles in Abeta
      generation. We will focus on the regulation of betaAPP cleavage through diverse
      signal transduction mechanisms and discuss possible points of therapeutic
      intercession in what has been postulated to be a seminal molecular step in the
      cascade of events terminating in the onset of dementia, a loss of neurons, and
      tragically, eventual death from Alzheimer's disease.

PMID- 9514985
TI  - Transcription by RNA polymerase I.
AB  - The genes that code for 45S rRNA, the precursor of 18S, 5.8S and 28S rRNA, are
      transcribed by RNA polymerase I. In many eukaryotes the genes are arranged as
      tandem repeats in discrete chromosomal clusters. rDNA transcription and rRNA
      processing occur in the nucleolus. In vertebrates, at least two factors, SL-1 and
      UBF, specific for transcription by RNA polymerase I cooperate in the formation of
      the initiation complex. Interestingly, there are proteins analogous to SL-1 in
      unicellular eukaryotes, but the requirement for a UBF-like factor appears to
      vary. Recent advances in our understanding of the rDNA transcription system and
      its regulation have demonstrated overlap with the other nuclear transcription
      systems (RNA polymerase II and III). This is exemplified by the utilization of
      TBP as a component of SL-1 and the role of Rb in regulatory rDNA transcription.

PMID- 9514991
TI  - Haematological disorders in liver disease.
AB  - The liver plays a central role in haemopoiesis and synthesis of coagulation
      proteins; liver disease is associated with a broad range of haematological
      abnormalities. Anaemia arises through multiple mechanisms, haem metabolism is
      disturbed, and liver disease causes alterations in red cell lipid metabolism.
      Defects of platelet number and function arise due to the effects of liver
      disease, immune mechanisms and hypersplenism. Coagulation disturbances are due to
      impaired vitamin K metabolism, defective synthesis of coagulation factors and
      regulatory proteins, impaired clearance of activated coagulation factors and
      increased fibrinolysis. Treatment, including blood component therapy, is
      discussed. Recent data indicate an emerging role for disturbances in Epo,
      cytokines (TNF, IL-6) and thrombopoietin in causing haematological changes in
      liver disease.

PMID- 9514992
TI  - Bone disorders in cholestatic liver diseases.
AB  - Osteopenia is a recognised complication of cholestatic liver diseases (CLD),
      usually ascribed to metabolic bone diseases such as osteomalacia or osteoporosis,
      with a prevalence from 10 to 56%, depending on the nature of liver disease.
      Primary biliary cirrhosis (PBC) is the condition causing osteopenia more
      frequently, but other cholestatic liver diseases like primary sclerosing
      cholangitis (PSC), haemochromatosis and alcoholic liver disease are also
      frequently associated with this disorder. The pathogenesis of bone disease in
      both adults and children with chronic cholestasis is not completely understood.
      There has been considerable disagreement regarding the relative importance of
      osteomalacia versus osteoporosis as the factors leading to osteopenia of liver
      disease. Osteopenia predisposes to atraumatic fractures, particularly in PBC
      patients undergoing orthotopic liver transplantation and treated with high
      corticosteroid doses. Bone mineral density measurement is the best way to assess
      the presence and severity of osteopenia in CLD patients, while laboratory tests
      give important information about the metabolic status of the bone. In this review
      prevalence data, diagnostic tools, pathophysiology and treatment of osteopenia in
      CLD are discussed.

PMID- 9514995
TI  - In this issue 
AB  - Copyright 1998 Academic Press Limited

PMID- 9514993
TI  - Pregnancy and liver disease.
AB  - Liver disease in pregnancy should be considered in 3 categories: pre-existing
      disease, disease peculiar to pregnancy and coincident acute liver or gall-stone
      disease. In addition the time of onset of diagnosis in terms of the trimester of
      gestation must be verified, as the diseases peculiar to pregancy have a
      characteristic time of onset. In the last trimester closes obstetric management
      is required for the constellation of abnormal liver function tests, nausea and/or
      vomiting and abdominal pain. This may be due to severe pre-eclampsia, HELLP
      (haemolysis, elevated liver enzymes and low platelets) syndrome or acute fatty
      liver of pregnancy with or without sub-capsular hepatic haematomas, amongst which
      there is an overlap. Early delivery is curative. A molecular basis consisting of
      long chain 3-hydroxyl CoA dehydroxegenase deficiency in heterozygote mothers
      underlies this clinical syndrome. Ursodeoxycholic acid is now established
      treatment for intra-hepatic cholestasis of pregnancy and appears to improve
      foetal outcome. Hepatitis B vaccination and immunoglobulin at birth prevents
      chronic hepatitis B in children of HBsAg (hepatitis B surface antigen) positive
      carrier mothers.

PMID- 9514994
TI  - Hepatitis C virus infection and cryoglobulinaemia.
AB  - Mixed cryoglobulins (CG) are serum proteins that precipitate at low temperature
      and are commonly classified into two types according to the presence (type II) or
      not (type III) of monoclonal immunoglobulins. Mixed CG are observed in a wide
      variety of diseases. Some mixed cryoglobulinaemia occurs without evidence of an
      underlying disease and is considered as essential mixed cryoglobulinaemia (EMC).
      Many studies have underlined the possible involvement of liver diseases in the
      pathogenesis of cryoglobulinaemia and particularly viral hepatitis. Recently, it
      has been shown that 50 to 80% of patients with EMC are in fact infected with HCV.
      It has also been shown that CG may be found in about 50% of patients infected
      with HCV. HCV-RNA genomic sequences are specifically concentrated in CG as well
      as IgG reactive with HCV-related proteins, and monoclonal IgM with rheumatoid
      factor (RF) activity. The monoclonal IgM RF detected in HCV infected patients is
      highly restricted to the same cross-idiotype OWAO. In addition to hepatocytes,
      HCV-RNA has been found in both peripheral blood and BM mononuclear cells. These
      cells could represent a reservoir of virus and may play a major role in viral
      persistence; they also could act as effectors of tissue injury in various organs.
      HCV shows high genomic variability. It is not clear whether these genetic
      variations have a significant clinical impact (i.e. severity of the disease) but
      there is evidence that they may influence both the efficacy of the host immune
      response and the interferon treatment response. The role of viral factors has
      been studied but a clear relationship between the presence of cryoglobulinaemia,
      the viral load or the HCV genotype have not been demonstrated. The frequency of
      clinical symptoms related to mixed cryoglobulinaemia reported in the literature
      is extremely variable according to the series. The striking association between
      HCV infection and mixed type II CG (usually considered as a benign
      lymphoproliferative disorder) and the occurrence of HCV infection in patients
      with NHL suggest that HCV could be involved in the pathogenesis of some malignant
      lymphoproliferative disease. The progression to malignancy probably involves the
      accumulation of multiple mutations facilitated by chronic antigenic stimulation.
      The efficacy of anti-viral treatment on both CG levels and related symptoms argue
      strongly that HCV is involved in the production of CG.

PMID- 9514996
TI  - Prevention of ischemic preconditioning only by combined inhibition of protein
      kinase C and protein tyrosine kinase in pigs.
AB  - In rabbits, inhibition of either protein kinase C or protein tyrosine kinase
      abolishes the infarct size reduction achieved by ischemic preconditioning. In
      pigs, however, inhibition of protein kinase C does not attenuate ischemic
      preconditioning. The present study tested whether inhibition of protein tyrosine
      kinase alone or in combination with inhibition of protein kinase C interferes
      with ischemic preconditioning in pigs. In 29 enflurane-anesthetized pigs, the LAD
      was cannulated and perfused from an extracorporeal circuit. Protein tyrosine
      kinase and protein kinase C were inhibited by continuous intracoronary infusion
      of genistein (5x10(-6) mol/l) and staurosporine (10(-7) mol/l), respectively.
      Subendocardial blood flow (ENDO) was measured with microspheres. Infarct size was
      analysed by TTC staining (% of LV area at risk) following 90 min low-flow
      ischemia and 120 min reperfusion. In the presence of genistein, 90 min ischemia
      at an ENDO of 0.06+/-0.01 (+/-s.e.m.) ml/min/g resulted in an infarct size of
      16.7+/-4.2% (n=8). With genistein, ischemic preconditioning by 10 min ischemia
      and 15 min reperfusion still reduced infarct size to 6.5+/-2.7% (ENDO: 0.05+/-0.
      01 ml/min/g, n=7, P<0.05). In the presence of both genistein and staurosporine,
      infarct size following 90 min ischemia was 14.1+/-3. 6% (ENDO: 0.06+/-0.01
      ml/min/g, n=7). With genistein and staurosporine, ischemic preconditioning no
      longer reduced infarct size significantly (11.5+/-3.1%, ENDO: 0.06+/-0.01
      ml/min/g, n=7). The effective attenuation of ischemic preconditioning only by
      simultaneous inhibition of both, protein kinase C and protein tyrosine kinase,
      suggests a complex signal cascade involving both protein kinases.

PMID- 9514997
TI  - NO missing link?

PMID- 9514999
TI  - Studies suggesting the participation of protein kinase A in 1, 25(OH)2-vitamin D3
      dependent protein phosphorylation in cardiac muscle.
AB  - We have previously established that the secosteroid hormone 1alpha, 25-dihydroxy
      vitamin D3 [1,25(OH)2D 3] rapidly stimulates dihydropyridine-sensitive calcium
      channel-mediated Ca2+ influx in chick cardiac muscle by a non-genomic action
      which is accompanied by phosphorylation of microsomal proteins. In the present
      study, we investigated the participation of the cyclic AMP/protein kinase A (PKA)
      signalling pathway in hormone-induced changes on protein phosphorylation in chick
      heart tissue. A major increase in the phosphorylation of a microsomal protein of
      45 kDa, and, to a lesser extent, of a protein of 70 kDa, was observed after
      incubation with [gamma-32P]ATP of membranes isolated from heart thin slices (HTS)
      pretreated for 1-5 min with 1,25(OH)2D3. This effect was dose- and time
      dependent, reaching a maximum after 3 min and at the physiological concentrations
      of 10(-10) and 10(-11) M. 1,25(OH)2D3 steadily increased cellular cAMP levels as
      a function of the dose (10( -12)-10(-9) M). The specific agonist of PKA, Sp-cAMPS
      and the PKA catalytic subunit stimulated the phosphorylation of the same membrane
      proteins as the hormone. The 1alpha,25-dihydroxy-vitamin D3-dependent changes in
      microsomal protein phosphorylation were diminished by the specific PKA inhibitor,
      Rp-cAMPS. In addition, the PKA activity ratio (-cAMP/+cAMP) increased 60% above
      the control after treatment of HTS with 10(-11) M 1,25(OH)2D3. The data obtained
      clearly indicate that activation of the cAMP/PKA signalling pathway mediates the
      stimulation of protein phosphorylation by 1alpha, 25-dihydroxy-vitamin D3 in
      chick cardiac muscle.

PMID- 9514998
TI  - Interleukin-1 in myocardium and coronary arteries of patients with dilated
      cardiomyopathy.
AB  - Idiopathic dilated cardiomyopathy (DCM) is characterised by a severe dysfunction
      of the heart muscle resulting in terminal heart failure. Its pathogenesis is
      believed to be multifactorial involving genetic predisposition, viral infection
      and autoimmunity, but little is known in detail, and there is no curative
      treatment except transplantation. Interleukin-1 (IL-1) mediates inflammatory
      responses to infection and injury. It can be produced by several widely
      distributed cell types, including macrophages, and is thought to depress myocyte
      contractility by stimulating nitric oxide synthase. To investigate whether this
      pro-inflammatory cytokine may be a pathogenic mediator in DCM, IL-1beta mRNA and
      protein were evaluated in coronary arteries and myocardium from patients
      undergoing cardiac transplantation for DCM.IL-1beta mRNA was detected by PCR of
      cDNA and northern blots of mRNA in coronary arteries and myocardium from patients
      with DCM. By comparison, samples from patients with ischaemic heart disease (IHD)
      contained much less IL-1beta mRNA. In contrast, mRNA for other cytokines
      (TNFalpha, IL-6, IL-10, PDGFA) were similar in both pathologies. In DCM, IL-1beta
      mRNA and protein were localised to infiltrating macrophages in interstitial
      regions between myocytes, some of the myocytes themselves, and endothelial cells
      of vessels in the wall of the arteries. These results suggest that local
      production of the pro-inflammatory cytokine, IL-1beta may play a part in the
      pathogenesis of DCM.

PMID- 9515000
TI  - 31P-NMR analysis of congestive heart failure in the SHHF/Mcc-facp rat heart.
AB  - 31P-NMR was used to monitor myocardial bioenergetics in compensated and failing
      SHHF/MCC-fa(cp) (SHF) rat hearts. The SHHF/Mcc-fa(cp) (spontaneous hypertension
      and heart failure) rat is a relatively new genetic model in which all individuals
      spontaneously develop congestive heart failure, most during the second year of
      life. Failing SHF rat hearts displayed a pronounced decrease in resting PCr:ATP
      ratios (P<0.001), which was explained by a significant (P<0. 0001) drop in total
      creatine (47.2+/-3.1 nmol/mg protein) v age matched controls (106+/-3 nmol/mg
      protein). In end stage failure, NMR determined PCr was 2.9+/-0.1 micro mol/g wet
      weight under basal conditions. In contrast, 6- and 20-month-old controls and
      compensated SHFs had PCr values of 5.3+/-0.1, and 5.1+/-0.5 and 5. 1+/-0.2 micro
      mol/g wet weight. Both compensated and failing SHF hearts were metabolically
      compromised when the rate pressure product (RPP) was increased, as evidenced by
      an increase in Pi and a drop in PCr. Compensated SHF hearts, however, were able
      to increase rate pressure products (RRP, mmHg X beats/min) from 44.5+/-1.4 to
      66.6+/-3. 4 K with dobutamine infusion, whereas hearts in end-stage failure were
      able to increase their RPP from baseline values of 27+/-4 K to only 37+/-7 K. The
      data indicate that a pronounced decline in PCr and total creatine signals the
      transition from compensatory hypertrophy to decompensation and failure in the SHF
      rat model of hypertensive cardiomyopathy.

PMID- 9515002
TI  - Coronary venous hypertension prevents the formation of the electrophysiological
      arrhythmogenic substrate of acute ischemia in the dog: salutary effects of
      preserved myocardial hydration.
AB  - Coronary venous hypertension induced by partial coronary sinus obstruction (CSO)
      in the dog, prevents or delays the predictable ventricular fibrillation (VF) of
      the early phase of acute ischemia. Also, CSO acting presumably through enhanced
      myocardial hydration, normalizes the inhomogenous extracellular potassium ([K+]o)
      accumulation, a major factor in producing the electrophysiological disparities,
      characteristic of arrhythmogenic substrate. To further clarify the mechanism of
      early ischemic VF prevention in dogs, radioactive microspheres were used to
      evaluate regional perfusion changes, resulting from CSO sufficient to raise the
      coronary sinus pressure to 40 mmHg, before and during ischemia induced by double
      coronary artery occlusion (CAO) (n=5). Also, global or regional unipolar
      electrogram mapping was used to assess changes of epicardial ventricular
      activation times (AT) and sequence and activation recovery intervals (ARI) during
      CSO, CAO and combined CSO and CAO, induced in random order (n=8). CSO did not
      affect regional perfusion nor improved collateral blood flow during ischemia.
      With CSO, AT shortened modestly over time (0.41+/-1.1 ms/min, r=0.85, P<0. 05)
      and ARI transiently decreased by up to 5.5%. With CAO, AT became variably delayed
      and isochrone map distortions were indicative of localized conduction delays or
      blocks, consistent with elevated [K+]o. In contrast, when CAO was preceded by
      CSO, AT delays were homogenous and normal activation sequence was preserved.
      Also, whereas with CAO, ARI shortened unequally over the ischemic region by as
      much as 43% at individual sites (average of 38.3+/-6.8 ms, P<0. 001), with
      combined CSO and CAO, ARI shortening was less pronounced and more homogenous
      (26.1+/-5.6 ms, P<0.05), not exceeding 29% at any site. Thus, in accordance with
      previous findings of enhanced [K+]o homogeneity, coronary venous hypertension
      reduces the disparities of activation and refractoriness of ischemia
      attributable, at least in part, to disparate [K+]o accumulation. Since no
      collateral blood flow improvement could be identified, the salutary
      electrophysiological effects of CSO may reflect a more homogenous extracellular
      environment, due to preservation of normal microvascular pressure (Pmv) and
      sustained filtration and lymph flow.

PMID- 9515001
TI  - Sarcoplasmic reticulum genes are selectively down-regulated in cardiomyopathy
      produced by doxorubicin in rabbits.
AB  - The clinical utility of doxorubicin, an antineoplastic agent, is limited by its
      cardiotoxicity. Our objective was to determine whether expression of genes
      encoding proteins that affect Ca2+ homeostasis were altered in the hearts of
      rabbits chronically treated with doxorubicin. Twelve male New Zealand white
      rabbits received an injection of doxorubicin (2.5 mg/kg i.v.) once a week for 8
      weeks. Eight rabbits were similarly injected with saline as controls. The cardiac
      function of both groups was evaluated 8 weeks after the final injection, as were
      the levels of expression of mRNA for Ca2+ transport proteins in the sarcoplasmic
      reticulum and plasma membrane. The amount of the sarcoplasmic reticulum Ca2+
      ATPase and the Ca2+ uptake capacity of the protein were also quantitated. Cardiac
      output was significantly decreased in the doxorubicin-treated group (71+/-21
      ml/min, P<0.05) compared with the control group (118+/-15 ml/min). The mRNA
      levels for the sarcoplasmic reticulum proteins were significantly diminished in
      the doxorubicin-treated hearts: ryanodine receptor-2 (relative expression level
      compared with controls, 0.35+/-0.13, P<0.01), sarcoplasmic reticulum Ca2+-ATPase
      (0.56+/-0.13, P<0.01), phospholamban (0.62+/-0.20, P<0.01) and cardiac
      calsequestrin (0. 57+/-0.26, P<0.01). In addition, both relative amount of
      sarcoplasmic reticulum Ca2+-ATPase protein (doxorubicin-treated group, 69+/-17%
      of control, P<0.01) and the Ca2+ uptake capacity (46. 9+/-9.8 nmol Ca2+/mg
      protein-5 min in doxorubicin group v 63.2+/-10. 4 in the control group, P<0.01)
      were concomitantly decreased with its mRNA expression level. Conversely, the mRNA
      levels for the plasma membrane proteins did not differ from those of control
      rabbits: the dihydropyridine receptor (relative expression level, 1. 03+/-0.30,
      N.S.), plasma membrane Ca2+-ATPase (0.93+/-0.33, N.S.) and the Na+/Ca2+ exchanger
      (0.87+/-0.34, N.S.). These findings suggest that a selective decrease in mRNA
      expression for sarcoplasmic reticulum Ca2+ transport proteins is responsible for
      the impaired Ca2+ handling, and thus, for the reduced cardiac function seen in
      the cardiomyopathy induced in rabbits by the long-term treatment with
      doxorubicin.

PMID- 9515003
TI  - RGS3 and RGS4 are GTPase activating proteins in the heart.
AB  - RGS family members are regulatory molecules that act as GTPase activating
      proteins (GAPs) for G alpha subunits of heterotrimeric G proteins. RGS proteins
      are able to deactivate G protein subunits of the Gi alpha, Go alpha and Gq alpha
      subtypes when tested in vitro and in vivo. Although the function of RGS proteins
      in cardiac physiology is unknown, their ability to deactivate Galpha subunits
      suggests that they may inhibit the action of muscarinic, alpha-adrenergic,
      endothelin, and other agonists. To evaluate the role of RGS family members in the
      regulation of cardiac physiology, we investigated the expression pattern of two
      RGS genes in normal and diseased rat heart tissue. RGS3 and RGS4 mRNAs and
      proteins were detected in adult myocardium. RGS3 and RGS4 gene expression was
      markedly enhanced in two model systems of cardiac hypertrophy: growth factor
      stimulated cultured neonatal rat cardiomyocytes and pulmonary artery-banded (PAB)
      mice. RGS3 and RGS4 mRNA levels were reduced in failing myocardium obtained from
      SHHF/Mcc-fa(cp) (SHHF) rats. These findings support the hypothesis that RGS gene
      expression is highly regulated in myocardium and imply that RGS family members
      play an important role in the regulation of cardiac function.

PMID- 9515004
TI  - Effects of chronic dietary creatine feeding on cardiac energy metabolism and on
      creatine content in heart, skeletal muscle, brain, liver and kidney.
AB  - Little is known about the regulation of total creatine concentration in heart,
      skeletal muscle, brain, liver and kidney in response to increased dietary
      creatine intake. The phosphorylated fraction of intracellular creatine
      (phosphocreatine) remain relatively constant, and therefore, higher intracellular
      creatine levels may increase the energy reserve of the heart [phosphocreatine and
      phosphoryl transfer via creatine kinase (CK)] and of other organs. To test the
      effect of supplying exogenous creatine on the myocardial energy reserve and on
      creatine content of various organs, rats were given chow containing 0
      (Untreated), 1, 3, 5, or 7% (of diet weight) creatine for ;40 days. Thereafter,
      hearts were perfused and left ventricular developed pressure and heart rate were
      recorded. High-energy phosphate concentrations were determined with 31P-NMR
      spectroscopy, CK reaction velocity by 31P-magnetization transfer. Total creatine
      was determined in heart, skeletal muscle, brain, liver, kidney and serum by high
      performance liquid chromatography (HPLC). Creatine feeding increased serum
      creatine by 73% (1% creatine), 142% (3%), 166% (5%) and 202% (7%). In the heart,
      increased serum creatine levels did not affect mechanical function; ATP,
      phosphocreatine, inorganic phosphate, CK reaction velocity and total creatine
      were all unchanged. Total creatine also remained constant in brain and skeletal
      muscle, while creatine content increased 4.6-fold in the liver and 1.9-fold in
      the kidney. We conclude that myocardial energy reserve via CK cannot be increased
      by exogenous creatine treatment.

PMID- 9515005
TI  - Incorporation of the troponin regulatory complex of post-ischemic stunned porcine
      myocardium reduces myofilament calcium sensitivity in rabbit psoas skeletal
      muscle fibers.
AB  - Decreased calcium sensitivity of tension in post-ischemic myocardium is thought
      to be a mechanism of depressed function in stunning. The purpose of this study
      was to determine if the decrease in calcium sensitivity of tension results from
      ischemia and/or reperfusion-induced alterations in the thin filament regulatory
      troponin. The experiments utilized an open-chest porcine model of regional LAD
      myocardial stunning that has previously been shown to cause a decrease in calcium
      sensitivity of tension in permeabilized myocytes. Stunning was induced by 45 min
      of low-flow ischemia to the left anterior descending (LAD) coronary artery
      perfusion bed, which was followed by 30 min of reperfusion. Regional LAD function
      after reperfusion was 0.5+/-2.8%, as assessed by systolic wall thickening (v
      23.9+/-4.1% thickening in control, P<0.001). Core biopsy samples from control
      circumflex and stunned LAD myocardium were acquired from each heart (n=9) after
      LAD reperfusion, and were used to obtain purified troponin complexes. Isometric
      tension-pCa relationships were measured in permeabilized psoas skeletal fibers
      before and after partial exchange of cardiac troponin from either control
      circumflex (n=6) or stunned LAD (n=8) myocardium for endogenous skeletal
      troponin. Calcium sensitivity of tension as assessed by pCa50 (i.e. pCa for half
      maximal tension) was unchanged after exchange of troponin from control circumflex
      myocardium (pCa50=5. 98+/-0.02 v 5.96+/-0.06), but there was a significant
      decrease in calcium sensitivity of tension after exchange of troponin from
      stunned LAD myocardium (pCa50=5.97+/-0.07 v 5.82+/-0.05, P<0.05). We conclude
      that the decrease in calcium sensitivity of tension in postischemic stunned
      myocardium is, in part, due to ischemia and/or reperfusion-induced alterations in
      the cardiac troponin regulatory complex.

PMID- 9515006
TI  - A new approach to assess viability of adult cardiomyocytes: computer-assisted
      image analysis.
AB  - OBJECTIVE: to develop a computerized procedure to obtain the percentage of rod
      shaped cells in preparations of isolated adult cardiomyocytes. METHODS: (1)
      isolated adult rat myocytes were either pretreated with a fixative (0.2%
      glutaraldehyde, 0.25% Triton X-100 and 0.1% trypan blue) or monitored via phase
      contrast optics without fixation; (2) an image field with several hundred cells
      was captured by a microscope-mounted video camera, which was connected to a frame
      grabber, and saved as a TIFF file; (3) the image was processed using Mocha
      software. Analysis consisted of setting the image threshold, an object count,
      automatic measurements of objects and their classification. RESULTS: though the
      software could measure many geometrical characteristics, a combination of two
      parameters, object size and shape factor, was found to be the most efficient.
      With these parameters, four classes of sample objects were constructed including
      rod-shaped myocytes, round damaged cells, overlapping cell clusters, and small
      debris. Test objects were classified automatically based on which sample object
      their parameters matched the most. Excellent correlation was obtained between
      manual counts and computer analysis of cell viability (r=0.98). CONCLUSION: a
      more efficient method, based on computer-assisted classification of objects, has
      been developed to assess the viability of isolated adult cardiomyocytes.

PMID- 9515007
TI  - Regulation of cardiac myocyte contractile function by inducible nitric oxide
      synthase (iNOS): mechanisms of contractile depression by nitric oxide.
AB  - Inflammatory cytokines have been implicated in the reversible depression of
      cardiac contractile function accompanying local or systemic immune stimulation.
      Incubation of cardiac myocytes with soluble components in the supernatant from
      cultured rat lung macrophages activated with endotoxin decreases their
      contractile response to beta-adrenergic stimulation through the induction of iNOS
      and the subsequent production of nitric oxide by these cells. In the present
      study, we characterize the mechanisms underlying NO's attenuation of adrenergic
      responsiveness in cardiac myocytes. iNOS was induced in cultured ventricular
      myocytes from adult rats by incubation for 20 h with conditioned medium from
      lipopolysaccharide (LPS)-activated macrophages. iNOS induction did not induce any
      alteration in beta-adrenergic receptor density or affinity, Galphai protein
      abundance, or adenylyl cyclase activity in cultured myocytes. Myocyte exposure to
      activated macrophage-conditioned medium markedly attenuated the elevation of cAMP
      in response to isoproterenol (Iso, 2 nM). Induction of iNOS with the macrophage
      conditioned medium also potentiated the Iso-induced increase in myocyte cGMP.
      This cGMP increase was totally abolished by NOS inhibitors. NOS inhibition also
      returned the attenuated cAMP response to 2 nM Iso to levels observed in control
      cells. Pre-incubation of the cells in isobutylmethylxanthine (IBMX), a
      phosphodiesterase inhibitor, also partly reversed the attenuation of cAMP
      increase with 2 nM Iso in cells expressing iNOS. Brief (15 min) exposure of
      myocytes to the NO donor, S-nitrosoacetylcysteine (SNAC, 100 micro M) which
      produced a three-fold increase in intracellular cGMP, also decreased by half the
      contractile response of cardiac myocytes to Iso (2 nM). We conclude that NO
      endogenously produced by iNOS decreases the intracellular levels of cAMP in
      response to beta-adrenergic stimulation in isolated cardiac myocytes, in part
      through a cGMP-mediated mechanism. This effect may participate in the NO
      dependent depression of cardiac function following cytokine exposure.

PMID- 9515008
TI  - Overexpression of phospholamban alters inactivation kinetics of L-type Ca2+
      channel currents in mouse atrial myocytes.
AB  - In mammalian ventricular myocytes, inactivation of L-type Ca2+ channels (CaCh) is
      controlled by voltage- and Ca2+-dependent mechanisms. The Ca2+-dependent
      component is regulated by the Ca2+ released from the sarcoplasmic reticulum (SR).
      However, little is known about the inactivation properties of CaCh in atrial
      myocytes, which lack spatial coupling between CaCh and SR Ca2+ release channels.
      The cardiac SR Ca2+ load is determined by the activity of SR Ca2+-ATPase, which
      is inversely regulated by the levels of phospholamban (PLB). To investigate the
      role of SR Ca2+ in atrial myocytes, Ca2+ currents (I Ca) were recorded in mouse
      atrial myocytes recorded from wild-type (WT) mice and the characteristics were
      compared to those obtained from atrial myocytes from the transgenic mice
      overexpressing PLB (PLB-OEX). ICa from WT exhibited fast and slow components of
      inactivation and the rate of inactivation was slowed when SR Ca2+ was depleted by
      caffeine, suggesting that the inactivation of atrial ICa is modulated by SR Ca2+
      load. The current density and voltage-dependence of ICa were similar between the
      two groups. However, the fast component of inactivation was significantly reduced
      in PLB-OEX. When Ca2+ was replaced by Ba2+ or in the presence of caffeine,
      inactivation was slowed and the decay of the current was not significantly
      different between WT and PLB-OEX. These results suggest that the inactivation of
      ICa in mouse atrial myocytes involves Ca2+-dependent and voltage-dependent
      components. The decrease in the faster component of inactivation in PLB-OEX is
      consistent with the idea that CaCh and SR Ca2+ release channels are functionally
      coupled and Ca2+ released from the SR contributes the Ca2+-dependent inactivation
      component.

PMID- 9515009
TI  - Inhibition of bicarbonate transport protects embryonic heart against
      reoxygenation-induced dysfunction.
AB  - It has not been well established whether the mechanisms participating in pH
      regulation in the anoxic-reoxygenated developing myocardium resemble those
      operating in the adult. We have specially examined the importance of Na+/H+
      exchange (NHE) and HCO3-dependent transports in cardiac activity after changes in
      extracellular pH (pHo). Spontaneously contracting hearts isolated from 4-day-old
      chick embryos were submitted to single or repeated anoxia (1 min) followed by
      reoxygenation (10 min). The chronotropic, dromotropic and inotropic responses of
      the hearts were determined in standard HCO3- buffer at pHo 7.4 and at pHo 6.5
      (hypercapnic acidosis). In distinct experiments, acidotic anoxia preceded
      reoxygenation at pHo 7.4. NHE was blocked with amiloride derivative HMA (1 micro
      mol/l) and HCO3-dependent transports were inactivated by replacement of HCO3 or
      blockade with stilbene derivative DIDS (100 micro mol/l). Anoxia caused transient
      tachycardia, depressed mechanical function and induced contracture. Reoxygenation
      temporarily provoked cardiac arrest, atrio-ventricular (AV) block, arrhythmias
      and depression of contractility. Addition of DIDS or substitution of HCO3 at pHo
      7.4 had the same effects as acidosis per se, i.e. shortened contractile activity
      and increased incidence of arrhythmias during anoxia, prolonged cardioplegia and
      provoked arrhythmias at reoxygenation. Under anoxia at pHo 6.5/reoxygenation at
      pHo 7.4, cardioplegia, AV block and arrhythmias were all markedly prolonged.
      Interestingly, in the latter protocol, DIDS suppressed AV block and arrhythmias
      during reoxygenation, whereas HMA had no effect. Thus, intracellular pH
      regulation in the anoxic-reoxygenated embryonic heart appears to depend
      predominantly on HCO3 availability and transport. Furthermore, pharmacological
      inhibition of anion transport can protect against reoxygenation-induced
      dysfunction.

PMID- 9515010
TI  - Both Na+-K+ ATPase and Na +-H+ exchanger are immediately active upon post
      ischemic reperfusion in isolated rat hearts.
AB  - Limited time resolution has hampered proper evaluation of changes in
      intracellular Na+ (Na+i) in whole hearts upon post-ischemic reperfusion. In
      isolated rat hearts perfused at 37 degrees C, we studied the contribution of the
      Na+-K+ ATPase and the Na+-H+ exchanger to control of Na+i during reperfusion
      using 23Na NMR and the shift reagent Tm(DOTP)5- with a time resolution of 5 s. To
      assess activities of the Na +-K+ ATPase and the Na+-H+ exchanger, 250 micro mol/l
      ouabain and/or 3 micro mol/l EIPA, respectively, was added to the perfusate
      during the first 5 min of reperfusion, following 20 min of ischemia. When used,
      ouabain was also present for 2 min prior to ischemia. Na+i increased during
      ouabain perfusion prior to ischemia (132+/-5 and 133+/-4% of the pre-ischemic
      control value after 2 min, in ouabain and ouabain+EIPA hearts, respectively;
      mean+/-s.e.m.; n=6 per group) resulting in higher end-ischemic values in ouabain
      and ouabain+EIPA hearts (249+/-9 and 267+/-17% of the pre-ischemic control value,
      respectively) than in control and EIPA hearts (207+/-21 and 199+/-10% of the pre
      ischemic control value, respectively). In ouabain, hearts Na+i started to rise
      directly upon reperfusion and amounted to 117+/-6% of the end-ischemic value
      after 60 s of reperfusion. In control hearts, however, Na+i dropped immediately
      and was 87+/-5% of the end-ischemic value after 60 s, indicating that the Na+-K+
      ATPase resumed function directly upon reperfusion. The initial steep increase of
      Na+i upon reperfusion in ouabain hearts, which diminished after approximately 40
      s to the rate of increase observed during ischemia, was absent in ouabain + EIPA
      hearts. This indicates the existence, although masked by Na+-K+ ATPase activity,
      of a Na+-H + exchange mediated Na+ influx upon reperfusion. If only EIPA was
      present during reperfusion the initial decrease in Na+i was faster than in
      control hearts, corroborating this finding.

PMID- 9515011
TI  - Lactate-induced vascular relaxation in porcine coronary arteries is mediated by
      Ca2+-activated K+ channels.
AB  - Under ischemic conditions and during strenuous exercise, lactate concentrations
      increase in coronary artery smooth muscle cells. Although lactate causes pH
      independent vasorelaxation, the mechanisms responsible for this effect are
      unclear. We investigated the effect of lactate on K+ channels in smooth muscle
      cells from porcine coronary arteries. Neutralized lactate (3-100 mm) induced
      vasorelaxation in ring segments of porcine coronary arteries precontracted with
      KCl in a dose-dependent manner. One millimolar tetraethylammonium (TEA), an
      inhibitor of Ca2+-activated K+ channels (KCa channels), reversed the lactate
      induced relaxation, while 60 microM glibenclamide, an inhibitor of ATP-sensitive
      K+ channels (KATP channels), did not. In both inside-out and cell-attached patch
      clamp technique with cultured smooth muscle cells, the KCa channels were
      activated by lactate. In inside-out patches, lactate activated KCa channels, even
      under acidic conditions. This is in contrast to the effect of H+ which
      inactivated KCa channels. We conclude that vasodilation of porcine coronary
      arteries induced by lactate is, at least in part, mediated by activation of KCa
      channels. This effect may be self-protective by maintaining coronary blood flow
      during ischemia.

PMID- 9515012
TI  - End-systolic pressure-dimension relationship of in situ mouse left ventricle.
AB  - The increasing popularity of genetically engineered mice in cardiovascular
      research has made it important to evaluate cardiac function in small animals. We
      have developed a system to enable simultaneous pressure-dimension analysis of the
      mouse left ventricle. The chest was opened under anesthesia, and a 1.4 F
      micromanometer catheter was inserted into the left ventricle through the apex. A
      pair of sonomicrometry crystals were attached to the anterior and posterior walls
      using tissue adhesive. Pressure and dimension were recorded simultaneously at
      baseline and after isoproterenol injection (1 micro g, intraperitoneally). The
      ascending aorta was occluded transiently to estimate the end-systolic pressure
      dimension relationship (ESPDR), which was parameterized subsequently by the
      quadratic equation: Pes=C2 X (Des-D0)2+E0 X (Des-D0), where Pes is end-systolic
      pressure, Des is end-systolic dimension, D0 is the dimension axis intercept, E0
      is the local slope at D0, and C2 is the curvilinearity coefficient. The maximum
      and minimum external dimensions at baseline were 5.82+/-0.50 (s.d.) mm and 5.49+/
      0.46 mm with fractional shortening of 0.057+/-0.014 (n=12). The ESPDR was
      significantly curvilinear and increased convexity after isoproterenol injection
      (C2, -444+/-281 to -1113+/-780 mmHg/mm2, P<0. 05; E0, 536+/-175 to 889+/-276
      mmHg/mm, P<0.001), while the dimension axis intercept remained relatively
      constant (D0, 5.39+/-0. 46 to 5.37+/-0.52 mm). In conclusion, the combination of
      miniature piezo-electric crystals and a micromanometer enables continuous
      measurement of pressure and dimension of in situ mouse left ventricle. This
      technology may be useful in evaluating the cardiac phenotype of genetically
      engineered mice.

PMID- 9515013
TI  - Biphasic effect of heat stress pretreatment on ischemic tolerance of isolated rat
      hearts.
AB  - Improvement of post-ischemic cardiac function 24 h after heat stress has been
      attributed to the increased cardiac tissue content of the inducible heat stress
      protein hsp70. Previous studies indicated that hsp70 is already significantly
      upregulated a few hours after heat stress. To delineate the relationship between
      hsp70 tissue content and heat stress-induced cardioprotection in the early time
      frame after heat stress, if any, post-ischemic functional recovery of isolated,
      ejecting rat hearts and the actual cardiac hsp70 content were investigated 0.5,
      3, 6 and 24 h after heat stress (42 degrees C for 15 min). Recovery (% of pre
      ischemic value) of cardiac output, left ventricular developed pressure, and
      positive and negative left ventricular dP/dtmax was studied during reperfusion
      after 45 min of global ischemia. Anesthetized non heat-stressed rats served as
      controls. The recovery of all hemodynamic variables was significantly worse in
      hearts isolated 30 min after heat stress than in control hearts. When the time
      interval between heat treatment and the ischemic episode was prolonged, a gradual
      improvement of post-ischemic functional recovery was observed. Only 24 h after
      heat treatment functional recovery was significantly better in the heat-stressed
      than in the control group. Compared to control hearts (0.27+/-0.10 mg/g total
      protein) cardiac hsp70 content was already significantly increased 0.5 h after
      heat stress (0.51+/-0.03 mg/g total protein). The cardiac hsp70 content further
      increased to 0. 70+/-0.11, 0.89+/-0.35 and 1.01+/-0.25 mg/g total protein, at 3,
      6 and 24 h after heat stress, respectively. The present findings clearly show
      that heat stress is associated with a fast rise in the myocardial hsp70 content
      which, however, is not uniquely correlated with improved ischemia tolerance of
      the treated hearts, which only occurs 24 h later.

PMID- 9515014
TI  - Probability of induction and stabilization of ventricular fibrillation with
      epinephrine.
AB  - Clinical studies suggest that epinephrine facilitates ventricular fibrillation
      (VF) although mechanisms remain unclear. We tested the hypothesis that
      epinephrine increases the probability of inducing VF and stabilizes VF in
      association with shortening of fibrillation action potential duration. VF was
      induced in isolated, New Zealand White rabbit hearts (n=16) under control
      conditions and in the presence of 0.9 micro M/l epinephrine. Monophasic action
      potentials were recorded during sinus rhythm, pacing, and fibrillation.
      Epinephrine reduced fibrillation p80 by 80%, from 23+/-4 to 4.6+/-1 V (P<0.05);
      and reduced fibrillation p90 by 82%, from 29.3+/-5.4 to 5.4+/-1.9 V (P<0.05).
      Epinephrine also reduced the probability of spontaneous termination of VF during
      the first 5 s of VF from 29 to 8% (P<0.05). Epinephrine significantly decreased
      mean fibrillation cycle length from 104.5+/-2 to 75.7+/-2.3 ms (P<0.001). Mean
      action potential duration (60% repolarization) decreased from 76+/-3 to 40+/-3 ms
      (P<0.0003). Frequency analysis showed a mean dominant frequency during VF of
      10.0+/-0.2 Hz under control conditions and 13. 3+/-0.3 Hz with epinephrine
      (P<0.0001). These results suggest that epinephrine increases the probability of
      VF induction and decreases the probability of spontaneous defibrillation.
      Stabilization of fibrillation is associated with shortening of action potential
      duration and fibrillation cycle length, which may allow a greater number of
      fibrillation waves in the ventricle.

PMID- 9515015
TI  - Protein tyrosine kinase is downstream of protein kinase C for ischemic
      preconditioning's anti-infarct effect in the rabbit heart.
AB  - The present study tested the hypothesis that one or more tyrosine kinase(s) are
      downstream of protein kinase C (PKC) in the signal transduction pathway
      responsible for the cardioprotective effect of ischemic preconditioning (PC).
      Isolated rabbit hearts were subjected to 30 min of regional ischemia followed by
      2 h of reperfusion. Infarct size was measured by triphenyltetrazolium staining
      and expressed as a percentage of the area at risk. Infarction in control hearts
      was 32.9+/-1.8%. Ischemic PC with 5-min ischemia/10-min reperfusion reduced
      infarct size to 11.5+/-1.5% (P<0.05). Infusion of the tyrosine kinase inhibitors,
      genistein (50 microM) or lavendustin A (0.5 microM), alone did not affect the
      level of infarction. When infused around the 5-min PC ischemia genistein failed
      to block protection (13.7+/-1.0%). However, when present at the onset of the 30
      min ischemia both genistein and lavendustin A completely aborted protection
      (31.4+/-2.0 and 28.1+/-1.5%, respectively). Activation of PKC by phorbol 12
      myristate 13-acetate (PMA, 0.05 nmol) was as protective is ischemic PC (14.9+/
      3.0%; P<0. 05). Similar to PC, PMA-induced protection was completely prevented by
      both genistein and lavendustin A. Conversely, anisomycin (50 ng/ml), an activator
      of MAP kinase kinases (dual tyrosine and threonine kinases), was very protective
      (7.5+/-1.6%; P<0.05) and this protection was still present when PKC was inhibited
      by 5 microM chelerythrine (12.1+/-1.6%; P<0.05). In conclusion, activation of a
      tyrosine kinase during the long ischemia appears to be required for
      cardioprotection in the rabbit heart. Furthermore, the ability of tyrosine kinase
      inhibitors to block PMA-induced protection in conjunction with the failure of PKC
      inhibition to prevent anisomycin-induced protection suggests that the tyrosine
      kinase is downstream of PKC and that the tyrosine kinase may be a MAP kinase
      kinase.

PMID- 9515016
TI  - Post-ischemic stimulation of 2-deoxyglucose uptake in rat myocardium: role of
      translocation of Glut-4.
AB  - Myocardial ischemia elicits translocation of the insulin-sensitive glucose
      transporter GLUT-4 from intracellular membrane stores to the sarcolemma. Because
      glucose metabolism is of crucial importance for post-ischemic recovery of the
      heart, myocardial uptake of [3H]-labeled 2-deoxyglucose and subcellular
      localization of GLUT-4 were determined during reperfusion in isolated rat hearts
      perfused with medium containing 0.4 mm palmitate and 8 mm glucose. Hearts were
      subjected to 20 min of no-flow ischemia, followed by reperfusion for up to 60
      min. Subcellular localization of GLUT-4 was determined by cell fractionation
      followed by immunoblotting. After 15 and 60 min of reperfusion uptake of 2
      deoxyglucose was significantly higher (91+/-9 and 96+/-8 nmol/min/g wet weight,
      respectively) as compared to control values (65+/-1 nmol/min/g wet weight).
      Ischemia elicited translocation of GLUT-4 to the sarcolemma, which persisted
      after 15 min of reperfusion. However, after 60 min of reperfusion the subcellular
      distribution of GLUT-4 was similar to control hearts. In conclusion, reversal of
      ischemia-induced translocation of GLUT-4 to the sarcolemma is rather slow,
      possibly facilitating glucose uptake early during reperfusion. However,
      myocardial uptake and phosphorylation of 2-deoxyglucose remains enhanced late
      during reperfusion, when pre-ischemic distribution of GLUT-4 is almost completely
      restored, indicating that additional mechanisms are likely to be involved in post
      ischemic stimulation of glucose uptake.

PMID- 9515017
TI  - U50,488H inhibits effects of norepinephrine in rat cardiomyocytes-cross-talk
      between kappa-opioid and beta-adrenergic receptors.
AB  - In order to determine the effect of kappa-opioid receptor agonist on the beta1
      adrenoceptor stimulation in the heart, the effects of norepinephrine (NE), a
      beta1-adrenoceptor agonist, on contraction and electrically induced intracellular
      calcium ([Ca2+]i) transient in the single rat ventricular myocyte pretreated with
      a kappa-opioid receptor agonist, trans-(+/-)-3, 4-dichloro-N-methyl-N-(2-[1
      pyrrolidinyl]cyclohexyl)-benzeneacetamide (U50,488H), at 0.01-1 microM were
      studied with a video edge tracker method and a spectrofluorometric method using
      fura-2 as calcium indicator, respectively. NE at 0.01-10 microM augmented both
      twitch amplitude and electrically induced [Ca2+]i transient dose-dependently,
      which were abolished by propranolol at 1 microM, a beta-adrenoceptor antagonist.
      The effects of NE on both contraction and [Ca2+]i transient were attenuated in a
      dose-dependent manner by U50,488H at 0.01-1 microM, which itself had no effect at
      all. The maximum response ( Emax) was decreased, while the concentration that
      produces 50% of the maximum response (EC50) was enhanced, by U50, 488H. The
      inhibitory effects of U50,488H on beta-adrenoceptor stimulation were completely
      blocked by pretreatment with norbinaltorphimine, a specific kappa-opioid receptor
      antagonist at 1 microM, or preincubation with pertussis toxin (PTX) at 200 ng/ml
      for 6 h. On the other hand, the inhibition on NE-induced augmentation in
      electrically induced [Ca2+]i transient by U50,488H was not affected by
      pretreatment with U73122, a specific inhibitor of phospholipase C (PLC), at 10
      microM for 30 min. U50,488H attenuated the augmentation of the electrically
      stimulated [Ca2+]i transient induced by forskolin at 0.1 and 0.5 microM. It did
      not, however, affect the augmentation of the electrically induced [Ca2+]i
      transient by N6, 2'-O-dibutyryl adenosine cyclic monophosphate (DB-cAMP). The
      results suggest that kappa-opioid receptor stimulation by U50,488H at 10(-6 )M or
      lower may inhibit the effects of beta-adrenoceptor stimulation by acting at a PTX
      sensitive G-protein and AC, but not via the phosphoinositol pathway.

PMID- 9515018
TI  - Proarrhythmic effects of pinacidil are partially mediated through enhancement of
      catecholamine release in isolated perfused guinea-pig hearts.
AB  - The contribution of adrenergic stimulation to the proarrhythmic effects of
      pinacidil (30 microM), an opener of ATP-sensitive potassium channels (K+ATP), was
      tested in an isolated guinea-pig heart model of global ischemia (10 min) and
      reperfusion (10 min). None (0%) of the control hearts (n=10) elicited arrhythmias
      during ischemia or reperfusion. In the pinacidil-treated group, one heart (5%)
      experienced episodes of ventricular tachycardia (VT)/fibrillation (VF) during
      normoxia. During ischemia, 63% (12 out of 19) of pinacidil-treated hearts
      exhibited episodes of VT or VF. Hearts not in VT or VF (n=7) at the time of
      reperfusion, exhibited 71% VT and 43% VT/VF upon reperfusion. Proarrhythmic
      effects of pinacidil during ischemia or reperfusion were completely reversed by
      glyburide (n=9; 10 microM), a K+ATP antagonist, or nadolol (n=9; 3 microM), a
      beta-adrenergic antagonist. Isoproterenol (n=10; 50 nM), a beta-adrenergic
      agonist, induced a 20% incidence of ischemic VT and VF, and a 70% incidence of
      reperfusion VF, while methoxamine (n=10; 10 microM), an alpha-adrenergic agonist,
      demonstrated little proarrhythmia (20% VT/VF at reperfusion only). Proarrhythmic
      effects of isoproterenol were reversed by nadolol, but not glyburide. Pinacidil
      caused a slight potentiation of tachycardia induced by a bolus injection of
      tyramine (30 micro g), an indirectly acting sympathomimetic, but bolus injections
      of pinacidil (100 micro g) had no effect on heart rate. Nisoxetine, a
      catecholamine uptake 1 inhibitor, had no proarrhythmic effects when given alone.
      Catecholamine levels were reduced in pinacidil-treated hearts relative to vehicle
      treated. In conclusion, it is suggested that the proarrhythmic effects of
      pinacidil following global ischemia and reperfusion in the isolated perfused
      guinea-pig heart appears to involve stimulation of beta-adrenoceptors. These
      proarrhythmic effects of pinacidil do not appear to be mediated solely through
      direct opening of K+ATP, but rather through an indirect enhancement of
      catecholamine release.

PMID- 9515019
TI  - AT2 receptor blockade reduces cardiac interstitial cell DNA synthesis and cardiac
      function after rat myocardial infarction.
AB  - The objective of the study was to investigate the involvement of angiotensin II
      receptor subtypes 1 and 2 in total interstitial cell and endothelial cell DNA
      synthesis and cardiac function after myocardial infarction (MI) in the rat. Rats
      with a MI were treated with either AT1 receptor antagonist GR138950C (2
      mg/kg/day) or the AT2 receptor antagonist PD123319 (3 mg/kg/day). Total
      interstitial cell (that is endothelial cells and fibroblast-like cells) DNA
      synthesis in the interventricular septum was significantly increased 2 weeks
      after MI. 33+/-3% of DNA synthesizing cells were identified as endothelial cells.
      PD123319, but not GR138950C significantly reduced total interstitial DNA
      synthesis. Both agents did not alter the fraction of DNA synthesizing endothelial
      cells. The effects on cardiac function were studied in parallel groups. MI
      reduced both cardiac output and stroke volume at 3 weeks after MI PD123319
      reduced CO, whereas GR138950C did not affect cardiac function. Thus, the data
      show that AT2 receptor blockade, but not AT1 receptor blockade early after rat
      myocardial infarction inhibits interstitial DNA synthesis and decreases cardiac
      function.

PMID- 9515021
TI  - In this issue 

PMID- 9515020
TI  - Differential effects of norepinephrine on contractile recovery of rat trabeculae
      following metabolic inhibition.
AB  - We have recently shown that norepinephrine (NE) pretreatment attenuates Ca2+
      overloading in cardiac rat trabeculae during metabolic inhibition (MI) with NaCN
      (2 mmol/l), and improves contractile recovery during a subsequent recovery period
      (RP). In the present study, we investigated the effects of the continuous
      presence of NE (1 micro mol/l), i.e. before, during and after MI, on Ca2+
      homeostasis maintenance and contractile recovery in the same model at 24 degrees
      C. In addition, we tested the effects of NE when only present in the rigor period
      during MI. The continuous presence of NE both before (30 min) and during MI (120
      min)+RP (60 min) (group NE-I) significantly increased the proportion of
      trabeculae that resumed to contract during RP from 46+/-4% (mean+/-s.e.m.) in
      controls to 82+/-8%. The Ca2+ rise at the end of MI in failing control trabeculae
      (1.85+/-0.04 micro mol/l) was more than doubled compared to recovering control
      preparations (0.78+/-0.02 micro mol/l). However, the time-course of the Ca2+ rise
      during MI in recovering and failing NE-I preparations was similar, and eventually
      of the same magnitude as observed in failing control preparations (1.6+/-0. 02
      and 1.85+/-0.07 micro mol/l, respectively). In contrast, when NE was present only
      in the rigor period during MI (group NE-II) the proportion of recovering
      preparations decreased significantly to 27+/-9%. Similar to the control group,
      recovering and failing preparations in group NE-II could be distinguished by a
      differential course in the Ca2+ rise during MI. The results show that when NE is
      present both before and during MI+RP, (i) recovery probability following MI is
      still improved, in spite of the deleterious effect on contractile recovery of the
      presence of NE in the rigor during MI, and (ii) there is no relationship between
      the magnitude of Ca2+ overload during MI and recovery probability during RP.

PMID- 9515022
TI  - Altered cardiac annexin mRNA and protein levels in the left ventricle of patients
      with end-stage heart failure.
AB  - Annexins are a unique family of membrane-associated, Ca2+ and phospholipid
      binding proteins found in various tissues. Among the 12 isoforms, Annexin II, V
      and VI exist in heart tissue in the highest amounts. Annexin VI has been shown to
      affect intracellular Ca2+ cycling and contractility in isolated cardiomyocytes.
      Annexin V is present in both cardiomyocytes and non-myocyte cell types in the
      heart and may play a role in the regulation of cellular ion fluxes, organization
      and secretion, while the cardiac effects of annexin II are unclear. To identify
      changes in annexin II, V and VI isoforms that might occur in human heart failure,
      we measured mRNA and protein levels of these three annexins in transplanted left
      ventricular tissue of 12 patients with end-stage congestive heart failure due to
      coronary artery disease (CAD, n=6) or idiopathic dilated cardiomyopathy (DCM,
      n=6) who underwent cardiac transplantation. Normal heart tissue (C, n=6) was used
      as a control. Northern blot analyses showed a significant decrease (61%) in
      annexin VI mRNA levels in heart failure patients compared with controls (1.08+/
      0.16 v 2.79+/-0.20 A.U.C. unit, determined by laser densitometry, mean+/-s.e.).
      In contrast, we found a 67% increase (2. 32+/-0.27 v 3.88+/-0.29) in annexin II
      mRNA levels and a two-fold increase (1.00+/-0.24 v 2.21+/-0.29) in annexin V mRNA
      levels in cardiomyopathic hearts as compared to normal hearts. Western blot
      analyses demonstrated a corresponding decrease (46.1%) in annexin VI protein
      levels in the heart failure group as compared to controls (2. 63+/-0.22 v 4.88+/
      0.52), while annexin II protein levels showed a significant 40.7% increase in
      patients with heart failure compared to those in normal hearts (5.08+/-0.67 v
      3.61+/-0.32). Annexin V protein levels were also significantly increased (45%) in
      heart failure patients compared with normal (2.14+/-0.19 v 1.48+/-0.11). No
      difference in either annexins II, V or VI mRNA and protein levels were found
      between CAD and DCM patients. We conclude that human end-stage heart failure is
      associated with a down regulation of annexin VI and up regulation of annexin II
      and V proteins. Coordinate changes were observed in steady-state mRNA levels.
      These results suggest that these annexin isoforms may contribute to the
      regulation of intracellular Ca2+ homeostasis in the cardiomyopathic heart.

PMID- 9515023
TI  - Determination of function in the isolated working mouse heart: issues in
      experimental design.
AB  - The goal of the present study was to compare two common types of isolated working
      mouse heart models, setting afterload either with (1) a hydrostatic fluid column,
      or (2) a mechanical resistor. Cardiovascular function in both models was
      determined by volume- and pressure-loading protocols. During volume loading, both
      models demonstrated a fixed degree of outflow resistance from the 20-gauge rigid
      aortic cannula resulting in a small predictable rise in left-ventricular
      pressure. In the mechanical resistor model, volume loading resulted in a marked
      increase in afterload, with a >50% increase from baseline aortic pressure. This
      altered ventricular mechanics, resulting in twice the expected change in dP/dt
      during volume loading. Additionally, coronary flow in the mechanical resistor
      model rose by more than four-fold in parallel to the increased preload. When
      using the fluid column model, however, aortic pressure was unchanged and coronary
      flow remained stable. During pressure loading, no significant differences in
      ventricular mechanics or coronary flow between the mechanical resistor and fluid
      column models were noted. When mouse hemodynamic data were compared to that from
      larger species, mouse hearts had similar cardiac function and efficiency with
      higher MVO2 and coronary flows. In summary, the hydrostatic fluid column isolated
      working mouse heart model is preferred over the mechanical resistor model for
      studying murine cardiac function. Further, use of this model provides hemodynamic
      data that is consistent with larger species, albeit with higher MVO2 and basal
      coronary flow, and should allow relevant study of mouse cardiac physiology.

PMID- 9515025
TI  - Myocardial fibrosis associated with aldosterone or angiotensin II administration:
      attenuation by calcium channel blockade.
AB  - Chronic administration of either angiotensin II (Ang II) or aldosterone (ALDO)
      leads to myocardial fibrosis. Myofibroblasts (myoFb) play a major role in
      collagen accumulation at sites of tissue repair. Pathophysiologic bases of
      cardiac fibrosis in such chronic primary or secondary hyperaldosteronism are
      under investigation. In vitro studies have shown that Ang II and ALDO each
      increase intracellular calcium and this second messenger is involved in altered
      fibroblast collagen turnover and growth. In the present study, we tested our
      hypothesis that calcium channel blockade would attenuate myocardial fibrosis that
      accompanies administration of either circulating Ang II or ALDO. Five animal
      groups were studied: (1) untreated age- and sex-matched control rats; (2) intact
      rats receiving Ang II (75 ng/min) for 2 weeks; (3) rats receiving Ang II plus
      mibefradil (30 mg/kg/day p.o.), a calcium channel blocker, for 2 weeks; (4)
      uninephrectomized rats receiving ALDO (0.75 microgram/h) together with a high
      salt diet for 6 weeks; and (5) uninephrectomized rats receiving ALDO and high
      salt diet plus mibefradil. Myocardial fibrosis was assessed by hydroxyproline
      concentration and interstitial and perivascular collagen volume fraction examined
      by videodensitometry on heart sections stained with collagen-specific picrosirius
      red. MyoFb were identified by immunohistochemical alpha-smooth muscle actin (SMA)
      labeling. ACE binding was determined by in vitro quantitative autoradiography.
      Compared to controls, in rats receiving either Ang II or ALDO we found: (1)
      myocardial fibrosis, expressed as microscopic scars, and perivascular fibrosis in
      both right and left ventricles with increased (P<0.05) hydroxyproline
      concentration and collagen volume fraction; (2) myoFb at sites of fibrosis, where
      high ACE binding density was also present; and (3) hydroxyproline concentration
      and collagen volume fraction were significantly (P<0.05) attenuated and the
      extent of alpha-SMA labeling and ACE binding density were each markedly (P<0.01)
      reduced in rats receiving either hormone plus mibefradil. This study therefore
      suggests calcium may modulate fibrous tissue formation in rat models of
      hyperaldosteronism by altering MyoFb collagen turnover and cell growth. It
      further is our contention that these findings implicate calcium as a signal used
      by effector hormones of the RAAS to promote tissue repair and that calcium
      channel blockade may offer advantage as a cardioprotective strategy in this
      setting.

PMID- 9515024
TI  - Persistent and heterogenous expression of the cyclin-dependent kinase inhibitor,
      p27KIP1, in rat hearts during development.
AB  - We have previously shown that there were differential and dramatic decreases of
      cyclin and cyclin-dependent kinase (CDK) activities in cardiomyocytes during the
      neonatal period. The activity of CDKs control cell cycle progression, and this
      activity is regulated positively and negatively by association of CDKs with
      cyclins and cyclin-dependent kinase inhibitors (CKIs), respectively. While the
      INK family (p15(INK4B)/p16(INK4A)/p18(INK4C)/p19(INK4D)) of CKIs is not
      detectable in hearts, the KIP/CIP family (p21(CIP1), p27(KIP1) and p57(KIP2)) of
      CKIs is detectable in most organs including the heart. Differential and dramatic
      changes of the KIP/CIP family (p21(CIP1), p27(KIP1) and p57(KIP2)) of CKIs were
      detected in rat hearts during development. The mRNA and protein levels of
      p21(CIP1) and p57(KIP2) were readily detectable in hearts at gestational and
      early postnatal periods and decreased thereafter. The mRNA levels of p27(KIP1) in
      ventricles were high during the gestational period, and did not change until day
      30 postnatal, then were decreased slightly in 90-day-old rats. The protein levels
      of p27(KIP1) increased significantly in the early postnatal period, then were
      expressed persistently, although levels decreased slightly in the adult period.
      However, protein levels of p27(KIP1) in atria did not change during development.
      Variable immuno-staining patterns of p27(KIP1) were observed at different periods
      of development and in various locations in myocardium. During the gestational
      period, approximately 35-50% of myocardial cells in the cardiac wall were
      p27(KIP1) immuno-positive and were distributed diffusely. These p27(KIP1)
      immunopositive cells increased predominantly in endocardial and mid-portion areas
      of ventricular myocardium at the early postnatal period. This heterogenous
      pattern of p27(KIP1) protein expression persisted to adult hearts though the
      percentage of p27(KIP1) immuno-positive cells decreased slightly. High
      magnification revealed that more than 50% of adult cardiomyocytes were p27(KIP1)
      immuno-positive and that p27(KIP1) was located solely in nuclei. These results
      indicate that p27(KIP1) may be an important inhibitor of CDK activities in
      cardiomyocytes during early postnatal development and may block the re-entrance
      of adult cardiomyocytes into the cell cycle after injury.

PMID- 9515026
TI  - Ras and rho are required for galphaq-induced hypertrophic gene expression in
      neonatal rat cardiac myocytes.
AB  - The hypertrophic response is characterized by increased myofibril/sarcomere
      organization, induction of the cardiac specific atrial natriuretic factor (ANF)
      and myosin light chain-2 (MLC-2v) genes, and an increase in total cell volume.
      The alpha1-adrenergic agonist phenylephrine induces both the morphological and
      biochemical markers of hypertrophy in cultured neonatal rat ventricular
      cardiomyocytes. Previous studies have suggested a functional requirement for the
      heterotrimeric G-protein, Galphaq, for a subset of the hypertrophic phenotypes.
      The small GTPases Ras and Rho have also been implicated in phenylephrine-induced
      hypertrophy. To further delineate the role of Galphaq in hypertrophy, a
      constitutively active mutant of Galphaq was transiently transfected in primary
      rat ventricular cardiomyocytes. This molecule was sufficient to induce ANF-, AP1
      , and MLC-2-driven gene expression. Co-transfection of Galphaq and dominant
      negative Ras or dominant negative Raf resulted in dose-dependent inhibition of
      ANF-driven expression. Both dominant negative Rho, and the Rho inhibitor C3
      transferase, also attenuated Galphaq- and Ras-induced ANF-driven gene expression.
      Cells transfected with active Galphaq did not show a detectable increase in
      activation of the mitogen activated protein kinases ERK or SAPK. However,
      activity of the MAP-kinases appears to be important for Galphaq-induced gene
      expression since the MAP-kinase phosphatase Clone 100 and catalytically inactive
      SAPK strongly inhibited Galphaq-induced ANF expression. Thus, our studies
      indicate Galphaq-induced hypertrophic gene expression requires the small G
      proteins Ras and Rho. The data also indicates that Galphaq mediated gene
      expression is dependent on functional MAP-kinases and that multiple signaling
      pathways contribute to Galphaq-mediated cardiac cell hypertrophy.

PMID- 9515028
TI  - Alteration of intracellular Na+ during ischemia in diabetic rat hearts: the role
      of reduced activity in Na+/H+ exchange against stunning.
AB  - To elucidate the contribution of reduced activity of Na+/H+ exchange in
      streptozotocin-induced diabetic hearts against stunning, intracellular Na+
      concentration ([Na+]i) was measured in isolated rat hearts using 23Na-MRS. The
      recovery of left ventricular developed pressure in hearts reperfused after 15 min
      global ischaemia at 37 degreesC was significantly better in diabetic ones
      (102.9+/-2.0% of pre-ischemic level, mean+/-s.e., n=6; P<0.05), and non-diabetic
      ones pre-treated with potent Na+/H+ exchange inhibitor, EIPA (1 mu mol/l; 93.8+/
      2.3%, n=5; *P<0.05) than non-treated, non-diabetic hearts (75.1+/-2.5%, n=8).
      When diabetic hearts were pre-treated with EIPA, the recovery (101.2+/-2.6%, n=5)
      was identical to that of non-treated, diabetic hearts. [Na+]i in non-diabetic
      hearts increased to 329.1+/-8.1% of pre-ischemic level during 15 min ischemia,
      whereas the increase in [Na+]i in diabetic hearts significantly suppressed to
      199.8+/-10.3% (P<0.001). EIPA attenuated the increase of [Na+]i during ischemia
      to 189.1+/-9.0% in non-diabetic hearts ( P<0.001) and to 155.3+/-4.6% in diabetic
      hearts (P<0.05). Thus, the EIPA-dependent Na+ accumulation during ischemia, i.e.
      Na+ influx probably mostly via Na+/H+ exchange was smaller in diabetic hearts by
      69.7% compared with that in non-diabetic hearts. These results indicate that the
      cardiac protection against stunning in streptozotocin-induced diabetic hearts is
      mediated by the attenuation of Na+ accumulation during ischemia, which is caused
      by the reduced activity in Na+/H+ exchanger.

PMID- 9515027
TI  - Staurosporine-induced apoptosis in cardiomyocytes: A potential role of caspase-3.
AB  - Cardiomyocyte apoptosis has been demonstrated in animal models of cardiac injury
      as well as in patients with congestive heart failure or acute myocardial
      infarction. Therefore, apoptosis has been proposed as an important process in
      cardiac remodeling and progression of myocardial dysfunction. However, the
      mechanisms underlying cardiac apoptosis are poorly understood. The present study
      was designed to determine whether the family of caspase proteases and stress
      activated protein kinase (SAPK/JNK) are involved in cardiac apoptosis. Cultured
      rat neonatal cardiac myocytes were treated with staurosporine to induce apoptosis
      as evidenced by the morphological (including ultrastructural) characteristics of
      cell shrinkage, cytoplasmic and nuclear condensation, and fragmentation.
      Nucleosomal DNA fragmentation in myocytes was further identified by agarose gel
      electrophoresis (DNA ladder) as well as in situ nick end-labeling (TUNEL).
      Staurosporine-induced apoptosis in myocytes was a time- and concentration-(0.25-1
      micro M)-dependent process. Staurosporine-induced apoptosis in myocytes was
      reduced by a cell-permeable, irreversible tripeptide inhibitor of caspases, ZVAD
      fmk, but not by the ICE-specific inhibitor, Ac-YVAD-CHO. At 10, 50 and 100 muM of
      ZVAD-fmk, staurosporine-induced myocyte apoptosis was reduced by 5.8, 39.1
      (P<0.01) and 53.8% (P<0.01), respectively. Staurosporine, at 0.25-1 micro M,
      increased caspase activity in cardiomyocytes by five- to eight-fold, peaking at 4
      8 h after stimulation. Based on substrate specificity analysis, the major
      component of caspases activated in myocytes was consistent with caspase-3
      (CPP32). Moreover, the appearance of the 17-kD subunit of active caspase-3 in
      staurosporine-treated myocytes was demonstrated by immunocytochemical analysis.
      In contrast, staurosporine induced a rapid and transient inhibition of SAPK/JNK
      in myocytes. The SAPK activity in myocytes was reduced by 68.3 and 58.3% (P<0.01
      v basal) at 10 and 30 min after treatment with 1 micro M of staurosporine,
      respectively. Our results suggest that staurosporine-induced cardiac myocyte
      apoptosis involves activation of caspases, mainly caspase-3, but not activation
      of the SAPK signaling pathway.

PMID- 9515029
TI  - Intracellular calcium, DNase activity and myocyte apoptosis in aging Fischer 344
      rats.
AB  - Myocyte apoptosis increases with age in Fischer 344 rats, but the multiple
      molecular events implicated in this phenomenon remain to be identified. Several
      defects involving Ca2+ homeostasis, pH, and the expression of p53 and genes of
      the Bcl-2 protein family may contribute to the activation of myocyte death.
      Therefore, changes in intracellular pH, cytosolic Ca2+, DNase I and DNase II were
      measured in myocytes isolated by enzymatic digestion from rats of different ages.
      Moreover, the expression of p53, Bcl-2 and Bax in these cells was determined.
      Measurements of intracellular pH by BCECF fluorescence at 3, 12 and 24 months
      showed that this parameter did not change with age: 3 months, 7.20+/-0.05; 12
      months, 7.21+/-0.07; 24 months, 7.18+/-0.09. In contrast, diastolic Ca2+
      determined by the Fura 2-AM method increased progressively from 99.8+/-1.9 nm at
      3 months to 136.3+/-9.6 nm at 24 months (P<0.001). Concurrently, DNase I activity
      evaluated by plasmid digestion assay in myocytes increased 3.2-fold from 3 to 24
      months (P<0.02). Conversely, pH-dependent-DNase II remained essentially constant
      with age. Western blotting performed on ventricular myocytes did not detect
      significant changes in p53, Bax and Bcl-2 proteins with age. Similarly,
      immunocytochemically, the fraction of myocytes labeled by p53, Bax and Bcl-2 did
      not change from 3 to 24 months. In conclusion, myocyte aging is characterized by
      an increase in diastolic calcium which may activate DNase I triggering apoptosis,
      independently from the expression of p53, Bax and Bcl-2 in the cells.

PMID- 9515030
TI  - Structure, regulation and function of avian glypican.
AB  - Glypicans are a group of membrane-bound heparan sulfate proteoglycans (HSPG) that
      are tissue specific and developmentally regulated. Transcripts for avian glypican
      are found in endocardial cushions, limb buds, somites and forebrain of early
      chick embryos. Since avian glypican is not well characterized, the cellular
      localization, regulation of expression, and possible function during cardiac
      development have been studied. A polyclonal antibody was raised against a 20
      amino acid peptide corresponding to an antigenic sequence within avian glypican
      core protein. The antibody recognized the expressed core protein in bacterial
      lysates and the endogenous HSPG in the proteoglycan fraction from chick
      forebrain. Immunolocalization studies indicated that the core protein is
      associated with cell membranes. The level of mRNA for avian glypican in MEQC (myc
      embryonic quail cardiomyocytes) grown in medium containing 10% fetal calf serum
      was compared to the message levels in cells grown without serum for 3 days. By
      Northern analysis, glypican transcripts were increased markedly after serum
      starvation. Up-regulation of glypican transcripts by serum withdrawal was
      partially prevented by addition of TGFbeta-1 and bFGF, suggesting that these
      growth factors may regulate its expression. MEQC cells deprived of serum migrated
      into clumps that could be blocked by an antisense OND (oligodeoxynucleotide) to
      the mRNA encoding the avian glypican. The same antisense OND inhibited the
      migration of endothelial cells from chick tubular heart explants over the surface
      of collagen gels. These results indicate that avian glypican may play a role in
      cell migration during development of endocardial cushions.

PMID- 9515032
TI  - Changes in E2F complexes containing retinoblastoma protein family members and
      increased cyclin-dependent kinase inhibitor activities during terminal
      differentiation of cardiomyocytes.
AB  - Cardiomyocyte terminal differentiation was examined by studying the interaction
      of retinoblastoma protein (pRb) family members with E2F during the developmental
      transition from 17-day fetal to 2-day neonatal. Additionally, the expression
      pattern of cyclins, cyclin-dependent kinases (CDKs), and CDK inhibitors
      responsible for modulating the phosphorylation of pRb were studied. p107, pRb,
      and p130 are regulators of cellular proliferation, differentiation, and cell
      cycle exit and entry, respectively. The active, underphosphorylated form of these
      proteins targets the E2F family of transcriptional factors that play a critical
      role in the control of genes associated with DNA synthesis. Electromobility shift
      analyses demonstrated E2F complexed with p107 in proliferating fetal
      cardiomyocytes, whereas in 2-day neonatal cells, E2F was principally associated
      with p130 and a low level of pRb. At the 2-day neonatal stage, decreased protein
      levels were observed for cyclins D2, D3, and E, and CDK2 and CDK4. No changes
      were observed in the mRNA levels of the D-cyclins in neonatal cells; however, the
      transcripts for cyclins A and E and CDK4 were diminished. In skeletal myoblasts,
      differentiation is associated with induction of p21, a CDK inhibitor, by a MyoD
      dependent pathway. Although heart cells lack MyoD, CDK assays demonstrated that
      the activity of CDKs 2, 4, and 6 were downregulated in 2-day neonatal cells, and
      CDC2 was increased. RT-PCR indicated that p21 mRNA was induced 1.4-, 2.0-, and
      3.1-fold in the 2-day neonatal, 7-day neonatal, and adult stages, respectively,
      compared to the 17-day fetal stage. At the protein level, p21 also increased at
      the 2-day neonatal stage. Kinase inhibitory immunodepletion assays showed that
      CDK inhibitory activity was markedly increased in the 2-day neonate. Although
      mRNA levels of the p27 CDK inhibitor were unchanged, its protein level and
      inhibitory effect on CDK2 and CDK4 were increased. Thus, cardiomyocytes retain
      the capacity to proliferate until the early neonatal period when a series of
      changes occur, including a switch in pRb partners, a decrease in CDK levels and
      induction of CDK inhibitory activity, which is associated with terminal
      differentiation.

PMID- 9515031
TI  - Transforming growth factor-beta1 and protein kinase C synergistically activate
      the c-fos serum response element in myocardial cells.
AB  - We previously reported that transforming growth factor-beta1 (TGF-beta1)
      potentiated alpha1-adrenergic and stretch-induced c-fos mRNA expression and
      norepinephrine (NE)-induced amino acid incorporation in rat cultured myocardial
      cells (MCs). In the present study, we attempted to explore the mode of TGF-beta1
      action for c-fos gene expression in MCs. In the transient transfection assay, TGF
      beta1 potentiated NE- or 12-O-tetradecanoylphorbol-13-acetate (TPA)-activated c
      fos promoter/enhancer, but not forskolin-activated c-fos promoter/enhancer. The c
      fos serum response element (SRE) and the TPA response element (TRE) were
      responsible for TGF-beta1-induced potentiation of the NE or TPA action. Although
      TGF-beta1 activated not only the wild-type c-fos SRE, but also the mutated c-fos
      SRE, which contains an intact binding site for the serum response factor (SRF)
      but lacks the ternary complex factor (TCF) binding site, TPA activated the wild
      type c-fos SRE but not the mutated c-fos SRE. TGF-beta1 did not potentiate the
      effects of TPA on the activation of mitogen-activated protein kinase (MAPK) and
      the phosphorylation of Elk-1 and SAP-1a, which belong to TCF at the c-fos SRE.
      These results indicate that TGF-betaf potentiates the c-fos SRE activated by PKC
      through the SRF binding site. TGF-beta1 is involved in the regulation of c-fos
      gene expression through the c-fos SRE and is subsequently involved in the
      regulation of the gene which has the TRE in the promoter/enhancer region.

PMID- 9515033
TI  - Relative importance of adenosine A1 and A3 receptors in mediating physiological
      or pharmacological protection from ischemic myocardial injury in the rabbit
      heart.
AB  - Although ischemic preconditioning (IP) in several species can be
      pharmacologically mimicked by selective adenosine A1 or A3 receptor agonists, it
      is currently unclear which receptor subtype (A1 and/or A3) is physiologically
      involved in mediating IP. To investigate this question, we determined (a) the
      affinity of adenosine for rabbit adenosine A1 and A3 receptors, and (b) the
      effects of selective rabbit A1 receptor blockade on IP and adenosine-mediated
      cardioprotection in a rabbit Langendorff model of myocardial ischemia-reperfusion
      injury. Adenosine was 19-fold selective for inhibition of N6-(4-amino-3
      [125I]iodobenzyl)adenosine (125I-ABA) binding to recombinant rabbit A1 v rabbit
      A3 receptors (A1 Ki: 28 nm; A3 Ki 532 nm). Buffer-perfused rabbit hearts were
      exposed to 30 min regional ischemia and 120 min of reperfusion, and infarct size
      was measured by tetrazolium staining and normalized for area-at-risk (IA/AAR).
      Ischemic preconditioning (5 min global ischemia and 10 min reperfusion) or
      adenosine (20 micro M, 5 min) perfusion reduced infarct size (IA/AAR) to 17+/-3
      and 14+/-2%, respectively (controls: 59+/-2%). Ischemic preconditioning and
      adenosine-mediated cardioprotection were completely blocked (57+/-2 and 61+/-4%
      IA/AAR, respectively) in the presence of a rabbit A1-selective concentration (50
      nm) of the antagonist BWA1433 (rabbit A1 Ki: 3 nm; A3 Ki; 746 n m). Thus, whereas
      recent studies have demonstrated that selective A1 or A3 receptor agonists can
      both pharmacologically mimic IP, the results of the present study suggest that
      the adenosine-mediated component of IP in the isolated rabbit heart is
      preferentially mediated by adenosine A1 receptors, potentially due to adenosine's
      selectivity for this receptor subtype.

PMID- 9515034
TI  - Constitutive and inducible hsp70s are involved in oxidative resistance evoked by
      heat shock or ethanol.
AB  - Improved cardiac post-ischemic recovery after whole-body hyperthermia is
      correlated with an increased expression of the heat shock proteins (hsps). The
      inducible hsp70 (hsp70i) has a known cardioprotective effect against
      ischemia/reperfusion injury. Here, we studied whether other hsps are also
      involved in cardioprotection. Using rat heart-derived H9c2 myocytes, we observed
      that preheating at 43 degreesC for 20 min conferred resistance to hydrogen
      peroxide (H2O2). The resistance to mild H2O2 toxicity (3-5 micro mol/10(7) cells)
      appeared early and persisted, whereas the resistance to moderate H2O2 toxicity (6
      9 micro mol/10(7) cells) was detectable only at 20-44 h post heat shock. No
      resistance was observed at higher doses of hydrogen peroxide (10-12 micro
      mol/10(7) cells), indicating that severe toxicity exceeds the capacity of the
      induced protective mechanism. Coincidentally, this thermal regimen elicited a
      rapid and prolonged increase in the cellular level of hsp70i, and a delayed and
      transient induction of the constitutive hsp70 (hsp70c). Nuclear translocations of
      hsp70i and hsp70c also occurred upon heat stimulation. A homogeneous distribution
      of the accumulated hsp70i and hsp70c throughout the nuclei and cytoplasm
      paralleled the development of heat-induced resistance to moderate H2O2 challenge.
      Application of another hsp inducer, ethyl alcohol, evoked a similar pattern of
      H2O2 resistance, and hsp induction and distribution. Our results suggest that
      induction and subcellular distribution of hsp70s contribute importantly to
      cellular antioxidant defenses, and that a co-operation between hsp70i and hsp70c
      may improve cardiac preservation during oxidative insult.

PMID- 9515035
TI  - Stable overexpression of the constitutive form of heat shock protein 70 confers
      oxidative protection.
AB  - We have previously reported that thermal preconditioning confers an oxidative
      resistance in rat heart-derived H9c2 myocytes. The development of this resistance
      is associated with a co-expression of both inducible (hsp70i) and constitutive
      (hsp70c) forms of the 70-kD heat shock proteins, suggesting an antioxidant role
      for these proteins. Overexpression of hsp70i has been shown to render cells more
      tolerant to oxidative challenge. The present study sought to determine whether
      increases in hsp70c, the constitutive member of this protein family, are also
      positively correlated to oxidative protection. A rat cDNA encoding hsp70c was
      inserted into a mammalian expression vector, allowing transcription of the
      inserted gene to be regulated by a powerful cytomegaloviral promoter. After
      introduction of this construct into H9c2 myocytes, stable clones were obtained.
      Western and Northern blot analysis of the derived clones showed a two-fold
      increase in hsp70c mRNA and protein concentrations. These clones were more
      resistant to thermal killing when compared to control cells transfected with the
      vector alone, implicating a functional role for the overexpressed hsp70c protein.
      hsp70c-enriched cells also exhibited a marked resistance to oxidative challenges,
      including exposure to hydrogen peroxide (H2O2), hydroxyl radical, menadione, and
      hypoxia/reoxygenation. These findings indicate that hsp70c overexpression
      provides a protective effect against endogenous or exogenously generated reactive
      oxygen species (ROS), suggesting that hsp70c actively participates in the heat
      shock-induced oxidative protection.

PMID- 9515036
TI  - Ambient pulsatile pressure modulates endothelial cell proliferation.
AB  - Many studies over the last decade have indicated that circulatory forces such as
      shear stress and cyclic strain can influence the endothelial cell (EC) phenotype.
      However, very little is known about the in vitro effects of pressure on EC. To
      study this, cultured bovine aortic EC were grown in custom designed pressure
      chambers with carefully regulated CO2/air environment. EC were exposed to either
      atmospheric, static (135 mmHg) or pulsatile pressure (160/110 mmHg). A pulsed
      pressure frequency of 60 cycles/min was maintained by computer-controlled
      solenoid valves, placed in series with pressure lines. EC proliferation was
      determined both by cell count after trypsin release on days 1,3 and 5 and by 3H
      thymidine incorporation. By day 5, a significant decrease in cell number occurred
      in both pressure groups, confirmed by the thymidine studies. No changes were
      observed in cell morphology and cell viability as assessed by LDH activity
      studies. To investigate the mechanism of this effect, EC conditioned media from
      the three pressure conditions were transferred to non-exposed, control EC.
      Significant cell growth inhibition was demonstrated in the control EC group
      treated with conditioned media from EC cultured under pulsatile pressure
      conditions. This finding suggests that EC exposed to pulsatile pressure secrete
      an autocrine factor with growth inhibitory properties. This effect was not
      mediated by the growth factors TGFbeta and IL-1 as shown by Northern blot
      analysis and antibody-neutralization studies.

PMID- 9515037
TI  - Low concentrations of adenosine receptor blocker decrease protection by hypoxic
      preconditioning in ischemic rat hearts.
AB  - A role for adenosine in ischemic preconditioning and hypoxic preconditioning (HP)
      has been established in several species but is controversial in rats, due in part
      to the inconsistency of the data from the different experimental design. Our
      objective was to investigate the role of adenosine in the protection of the
      ischemic myocardium by HP in rats. METHODS: perfused hearts isolated from Sprague
      Dawley rats were exposed to 5 min of hypoxic perfusion before 25 min of global
      ischemia followed by 20 min of reperfusion. The effects of adenosine receptor
      antagonist, 8-(p-sulfophenyl)-theophylline (8SPT) on HP-based changes in left
      ventricular function, energy metabolites, and release of creatine kinase and
      lactate dehydrogenase were determined. To minimise non-specific effects of 8SPT,
      low concentrations of agent (0.5 or 1.0 micro mol/l) were used. RESULTS: 8SPT
      alone had no deleterious effects on normoxically perfused hearts or on
      ischemic/reperfused hearts. HP improved the recovery of LV function and creatine
      phosphate, and reduced the release of enzymes during reperfusion. 8SPT (1.0
      micromol/l) ameliorated the beneficial effect of HP on cardiac function, but did
      not reverse the reduction in release of enzymes by HP completely. CONCLUSION:
      results suggest that the protective effect of HP on myocardial contractile
      function may be mediated by receptor(s) that can be inhibited by low
      concentrations of antagonist but may not have a primary role in the reduction of
      cellular damage by HP in rats.

PMID- 9515038
TI  - Alterations in cardiac gene expression during ventricular remodeling following
      experimental myocardial infarction.
AB  - Following myocardial Infarction (MI) the heart undergoes a process of remodeling
      characterized by considerable hypertrophy of the non-infarcted myocardium. We
      have recently characterized the molecular basis of key electrophysiologic
      alterations that may provide insight into the arrhythmogenecity of post-MI
      remodeled hypertrophied myocardium. To further characterize other key alterations
      in the pattern of cardiac gene expression in a time-dependent manner, we have
      measured mRNA and immunoreactive protein levels of selective cardiac genes in the
      remodeled hypertrophied left-ventricular (LV) myocardium of rats, 3 and 21 days
      after left-coronary ligation and compared the results with sham-operated rats.
      RNase protection assay was performed to assess the expression of c-fos, atrial
      natriuretic factor (ANF), brain natriuretic factor (BNF), alpha2/3 isoform of Na
      K ATPase, cardiac alpha/beta isoform of myosin heavy chain (MHC). Compared to the
      sham group, the expression of c-fos was increased 10-fold (P<0.02) in the MI
      group on day 3, but unlike other overload hypertrophy models, the expression
      remained elevated by three-fold on day 21. Similar to other overload models, the
      ANF and BNF expression increased significantly. No alterations were observed in
      the expression of cardiac alpha-actin. There was reexpression of the fetal
      isogene form of MHC and Na-K ATPase after MI. The beta-MHC mRNA levels, the fetal
      isoform of MHC, returned to basal levels after 21 days. After an initial five
      fold decrease the adult isoform of alphaNa-K ATPase, alpha2 Na-K ATPase mRNA,
      returned to control levels and similar changes were seen in the corresponding
      protein levels. These findings indicate that during LV remodeling and hypertrophy
      following MI, there is an upregulation of early response genes and fetal isogene
      expression. The pattern of activation, however, is distinct from that observed in
      other overload models, indicating the possible involvement of alternate signal
      transduction pathways.

PMID- 9515039
TI  - Dissociation of intracellular sodium from contractile state in guinea-pig hearts
      treated with ouabain.
AB  - The positive inotropic effect of cardiac glycosides has been attributed to
      inhibition of the Na-K-ATPase, accumulation of intracellular sodium and enhanced
      calcium availability due to Na-Ca exchange. However, few measurements of
      intracellular sodium in the functioning left ventricle following ouabain exposure
      at therapeutic doses are available. Our experimental objective was to quantitate
      the relationship between contractile state and intracellular sodium measured by
      23Na nuclear magnetic resonance spectroscopy or atomic absorption in the intact
      heart. Isolated guinea-pig hearts, perfused in the Langendorff mode, were paced
      and then exposed to ouabain (3x10(-7)m) for 30 min. Left-ventricular pressure was
      monitored continuously. Intracellular sodium was measured either at 1-min
      intervals throughout the perfusion by shift reagent-aided 23Na nuclear magnetic
      resonance spectroscopy in the beating heart or following 30 minutes of perfusion
      by atomic absorption in myocardial tissue. While treatment with ouabain was
      associated with almost a two-fold rise in developed pressure, there was no
      significant increase in intracellular sodium measured by either technique. Thus,
      the positive inotropic effect of ouabain in this model is not associated with
      significant changes in bulk intracellular sodium. However, these results do not
      exclude the possibility of shifts between intracellular pools which would not be
      detected in bulk measurements, or changes in NMR-invisible intracellular pools
      which are not detectable by single quantum spectroscopy techniques.

PMID- 9515040
TI  - Sarcoplasmic reticulum Ca2+ pump blockade decreases O2 use of unloaded
      contracting rat heart slices: thapsigargin and cyclopiazonic acid.
AB  - We previously established a new measuring method of the myocardial O2 consumption
      of mechanically unloaded rat left-ventricular slices. O 2 consumption of
      unstimulated myocardium corresponds to basal metabolism. We have found O2
      consumption of stimulated myocardium to include basal metabolism and O 2
      consumption for Ca2+ handling in the excitation-contraction coupling, but not for
      crossbridge cycling. Thus, O2 consumption for the excitation-contraction coupling
      is obtained by subtracting basal metabolism from O2 consumption of the stimulated
      myocardium. We have shown that O2 consumption for the excitation-contraction
      coupling corresponds to 40% of basal metabolism. The purpose of the present study
      was to analyse the component of myocardial O2 consumption for the excitation
      contraction coupling by this method. Blockade of the sarcoplasmic reticulum Ca2+
      pump by thapsigargin (0.1-1 micro mol/l), or by cycloplazonic acid (10 micro
      mol/l), significantly reduced O2 consumption for the excitation-contraction
      coupling by 40 or 70% of the respective controls. Neither thapsigargin nor
      cyclopliazonic acid reduced basal metabolism O2 consumption. The magnitude of
      free shortening of the unloaded myocardial slices, quantified by slice surface
      area reduction, was small (about 1.5%) because of the lack of external preload.
      Thapsigargin (1 micro mol/l) and cycloplazonic acid (10 micro mol/l) markedly
      attenuated the already reduced free shortening. 2,3-butanedione monoxime (5
      mmol/l) also largely suppressed the free shortening, although this agent did not
      alter the O2 consumption of either unstimulated or stimulated myocardium. Some
      residual cross-bridge cycling may occur without detectable O2 consumption. Our
      present energetic results revealed that the O2 consumption of myocardial slices
      for the Ca2+ handling in the excitation-contraction coupling was mainly used for
      the sarcoplasmic reticulum Ca2+ pump.

PMID- 9515041
TI  - Interaction of hypoxia and aging in the heart: analysis of high energy phosphate
      content.
AB  - To test the hypotheses that aged myocardium has lower ATP concentration and that
      a greater ATP hydrolysis during hypoxia exaggerates diastolic dysfunction in aged
      myocardium, we used 31P NMR spectroscopy to measure ATP and phosphocreatine (PCr)
      contents combined with heart function at baseline and during hypoxia and
      reoxygenation in perfused hearts isolated from young adult (3-4 months old) and
      old (24-25 months old) Fisher 344 rats. At baseline, old hearts had 30% lower
      heart rate and prevalent supraventricular arrhythmia; they had lower PCr and
      creatine contents (approximately 30%) but normal ATP content. Hypoxia caused
      similar decreases in heart rate and rate pressure product in young and old
      hearts. There was a two-fold increase in left-ventricular end-diastolic pressure
      (LVEDP) in young adults, but, surprisingly, no change in LVEDP in old hearts. ATP
      decreased similarly in hearts from young and old rats, but the PCr decrease was
      two-fold smaller in old hearts during hypoxia. Superimposition of pacing on
      hypoxic old hearts caused six-fold increase in LVEDP; although utilization of PCr
      increased, it was still incomplete. We conclude that PCr is incompletely used to
      maintain ATP level during hypoxia especially in the senescent heart, and that the
      increase in LVEDP in old hearts cannot be explained solely by changes in indices
      of bioenergetics.

PMID- 9515043
TI  - Ischemic preconditioning: effects on pH, Na and Ca in newborn rabbit hearts
      during Ischemia/Reperfusion.
AB  - In adult hearts, ischemic preconditioning (PC) has been shown to decrease
      ischemia-induced changes in intracellular pH (pHi) and [Ca] ([Ca]i) and decrease
      associated injury. These results are consistent with the interpretation that PC
      decreases the stimulus for Na uptake via Na/H exchange, thereby decreasing
      intracellular Na (Nai) accumulation, and thus decreasing the change in force
      driving Na/Ca exchange, which otherwise contributes to ischemia-induced increases
      in [Ca]i. Given documented age-related differences in myocardial responses to
      ischemia, we tested the hypothesis that in newborn hearts, PC will diminish
      intracellular [H], Nai, and [Ca]i during ischemia/reperfusion. NMR was used to
      measure pHi, Nai, [Ca]i, ATP, and PCr in isolated newborn (4-7 days) rabbit
      hearts Langendorff-perfused with Krebs-Henseleit solution equilibrated with 95%
      O2/5% CO2 at 36+/-1 degrees C. Control hearts were perfused 30 min before
      initiating 40 min global ischemia followed by 40 min reperfusion. PC hearts were
      treated the same except four 5-min intervals of ischemia each followed by 10 min
      of perfusion which preceded global ischemia. At end ischemia, pHi was higher in
      PC than control hearts (6.31+/-0.03 v 5.83+/-0.05; P<0.05). Similarly, PC
      diminished Nai-accumulation during ischemia and reperfusion (P<0.05). Control Nai
      rose from 16.2+/-2.6 to 108.8+/-10.3 (mEq/kg dry weight) and recovered to 55.2+/
      10.1 and the corresponding values for PC hearts were 25.6+/-6.2, 70.0+/-7.9 and
      21.9+/-5.2. PC also improved [Ca]i recovery during reperfusion (P<0.05). Control
      [Ca]i rose from 418+/-43 to 1100+/-78 (nm/l) and recovered to 773+/-63, whereas
      in PC hearts the values were 382+/-40, 852+/-136 and 371+/-45, respectively. In
      addition, PC decreased coronary resistance during reperfusion (P<0.05) as
      reflected by lower perfusion pressures under constant flow conditions (65.9+/-1.5
      v 56. 1+/-4.1 mmHg at end of reperfusion). Finally, PC improved recovery of left
      ventricular developed pressure (LVDP-43.8+/-12.0 v 17.2+/-3. 0% of control;
      P<0.05) and diminished CK release (607+/-245 v 2432+/-639 IU/g dry weight;
      P<0.05) during reperfusion. The results are consistent with the hypothesis.

PMID- 9515042
TI  - Adenine/ribose supply increases adenosine production and protects ATP pool in
      adenosine kinase-inhibited cardiac cells.
AB  - The objective of the present study was to establish the optimal combination of
      inhibitors of adenosine metabolism and nucleotide precursors resulting in long
      term increase in endogenous adenosine concentration without adverse metabolic
      consequences in non-ischemic cardiomyocytes and endothelial cells. Cardiomyocytes
      and endothelial cells were isolated after collagenase digestion of the rat heart.
      Freshly isolated cardiac myocytes or cultured endothelial cells were incubated
      for up to 8 h with no inhibitors or substrates or with various combinations of
      adenosine deaminase inhibitor: 5 micron M erythro-9(2-hydroxy-3-nonyl)adenine
      (EHNA), adenosine kinase inhibitors: 10 micro M 5'-iodotubercidin (ITu) or 10
      micro M 5'-aminoadenosine (AA) and nucleotide precursors: 100 micro M adenine,
      2.5 mm ribose and 5 mm inorganic phosphate. Nucleotide, nucleoside and base
      concentrations were evaluated at the end of the incubation by HPLC in
      cardiomyocyte or endothelial cells extracts and in incubation media. Adenosine
      content in cardiomyocyte suspension was enhanced after 3 h incubation in the
      presence of ITu+EHNA as compared to EHNA alone (2.8+/-0.2 v 0.9+/-0.2 nmol/mg
      protein, respectively). ATP decreased from an initial value of 22.7+/-0.7 nmol/mg
      protein to 18.9+/-0.7 in the presence of ITu+EHNA, while ATP was maintained at
      21.8+/-0.7 nmol/mg protein with EHNA. With adenine+ITu+EHNA, the changes were
      similar to those observed with ITu+EHNA. However, with ribose+adenine+ITu+EHNA,
      ATP increased to 25. 8+/-1.2 nmol/mg protein and adenosine concentration was
      elevated to 3.9+/-0.3 nmol/mg protein. Similar results were observed if AA was
      used instead of ITu to inhibit adenosine kinase. All the changes were maintained
      after 8 h of incubation. Adenosine content was increased in endothelial cells
      incubated with ITu+EHNA to 3.1+/-0.4 nmol/mg protein as compared to 1.1+/-0.2
      nmol/mg protein with EHNA alone after 3 h, while ATP decreased (18.1+/-1.1 v
      22.0+/-1.4 nmol/mg protein with EHNA+ITu or EHNA, respectively). In the presence
      of adenine+ITu+EHNA, adenosine content increased after 3 h to 6.5+/-0.9 nmol/mg
      protein while ATP was elevated to 26.1+/-0.8 nmol/mg protein. Additional presence
      of ribose was without effect. No changes in adenylate energy charge were observed
      in cardiomyocytes or endothelium under any conditions studied. Inhibition of
      adenosine kinase and adenosine deaminase caused a decrease in ATP together with
      increased adenosine content both in endothelial cells and cardiomyocytes.
      However, the addition of adenine (endothelial cells) or adenine with ribose
      (cardiomyocytes) together with inhibitors of adenosine metabolism protected cells
      from ATP depletion and further increased adenosine concentration.

PMID- 9515044
TI  - Carbohydrates and purines in underperfused hearts, protected by ischemic
      preconditioning.
AB  - Few results, and those controversial, have been published on ischemic
      preconditioning followed by low-flow ischemia. The aim of this study was to
      assess whether ischemic preconditioning: (1) confers protection against severe
      underperfusion; and (2) is mediated by mobilization of proglycogen, resulting in
      increased anaerobic glycolysis and reduced myocardial injury. Isolated rat hearts
      were retrogradely perfused and subjected to either 25 min low-flow ischemia (0.6
      ml/min) followed by 30 min reperfusion (IC; n=5), or the same protocol preceded
      by two cycles of 5 min no-flow ischemia and 5 min reperfusion (PC; n=7).
      Additionally, hearts (n=52) were freeze-clamped at different time points
      throughout the protocol. Preconditioning improved functional recovery (developed
      force X heart rate in PC hearts: 54 v 21% in IC hearts; P<0.01) and reduced
      ischemic damage (cumulative release of creatine kinase during reperfusion: 93 v
      215 micro/g dry weight; P<0.05). During ischemia and reperfusion, release of
      adenosine and the sum of purines was smaller in PC hearts (P<0.05), while lactate
      release was similar in the two groups. PC reduced both macroglycogen and
      proglycogen by c. 60% (P<0.01) resulting in constant glycogen levels during low
      flow ischemia. In contrast, in IC hearts, both fractions decreased by c. 60%
      during underperfusion (P<0.01). These results demonstrate that: (1) ischemic
      preconditioning reduces injury due to severe flow reduction; and (2)
      preconditioning reduced glycogenolysis without affecting anaerobic glycolysis,
      suggesting increased glucose uptake.

PMID- 9515045
TI  - Metabolic fate of glucose in vascular smooth muscle during contraction induced by
      norepinephrine.
AB  - The metabolism of glucose in porcine carotid artery was tracked by isotopic
      methods during sustained isometric contraction induced by 100 microM
      norepinephrine (NE). In resting muscles, 74 and 18% of glucose taken up was
      accounted for by glycolysis and glycogen synthesis, respectively. Lactate
      production accounted for 69%, pyruvate production for 12%, and glucose oxidation
      accounted for 14% of glycolytic flux. The oxidation of glucose accounted for 57%
      of the consumption of O2 and thus constituted the primary oxidative substrate.
      During contraction by NE, glucose-uptake declined modestly below the resting
      basal rate. Glycolysis of external glucose and lactate production decreased and
      then increased with sustained contraction. Norepinephrine stimulated simultaneous
      glycogenolysis and glycogen synthesis, with net glycogen synthesis prevailing
      over 90 min of isometric contraction. Furthermore, NE modified the distribution
      of glucosyl units throughout the glycogen pool. The steady state rate of
      oxidation of glucose did not increase during NE contraction, even though O2
      consumption increased. In contrast, increased glucose oxidation was demonstrable
      during contraction induced by 80 mm KCl. Furthermore, oxidation of exogenous
      fatty acid could be demonstrated during NE-induced contraction. Thus, NE exerts
      multiple effects on glucose and glycogen metabolism in smooth muscle, but it does
      not stimulate glucose oxidation.

PMID- 9515047
TI  - The development of the food motivation scale.

PMID- 9515046
TI  - MK-801 interferes with nutrient-related signals for satiation.

PMID- 9515048
TI  - Abstracts
AB  - Copyright 1998 Academic Press Limited

PMID- 9515049
TI  - Sex-biased mortality in woodrats occurs in the absence of parental intervention
AB  - Male-biased mortality in young animals is often viewed as adaptive discrimination
      against male offspring by parents unable to raise reproductively competitive
      sons. Unequivocal evidence of the presence or absence of parental discrimination
      against males is lacking, however, and the adaptive interpretation of male-biased
      mortality is confounded by an alternative explanation that it reflects
      differential energetic requirements between the sexes (due to sexual selection
      for large size in mature males) independent of parental manipulation. To
      determine whether maternal discrimination against offspring explains postnatal
      mortality in a sexually dimorphic rodent, we examined patterns of growth and
      mortality in offspring of food-restricted and food-enriched lactating bushy
      tailed woodrats, Neotoma cinerea. We also monitored mothers and their litters
      daily throughout lactation for evidence of maternal discrimination against
      offspring. Offspring of food-restricted mothers showed depressed growth, and
      mortality of offspring born to both food-restricted and food-enriched mothers was
      male-biased, but in the absence of maternal discrimination. Offspring that died
      were no less likely to be attached to their mother's teats in the 10 days prior
      to death than were offspring that successfully weaned. Similarly, offspring of
      food-restricted mothers were attached as often as were offspring of food-enriched
      mothers. In a series of behavioural arena trials in the first 10 days after
      birth, restricted mothers were no less attentive toward their sons than they were
      to their daughters, nor did mothers treat their offspring that did not survive to
      weaning differently from those that survived. Our findings provide empirical
      evidence that postnatal, sex-biased mortality in offspring is not necessarily due
      to parental intervention, and they call into question the adaptive
      interpretations of previous examples of sex-biased offspring mortality. Copyright
      1998 The Association for the Study of Animal Behaviour Copyright 1998 The
      Association for the Study of Animal Behaviour.

PMID- 9515050
TI  - Body fat and time of year interact to mediate dispersal behaviour in ground
      squirrels
AB  - Behaviour is often influenced by energy availability. Hibernation presents an
      energetic challenge to Belding's ground squirrels, Spermophilus beldingi, which
      depend entirely on stored energy for survival during their 8-9 month dormant
      period each year. Dispersal from the natal area may also place energetic demands
      on S. beldingi. In this study, we assessed the relationship between dispersal
      behaviour, body mass and body fat of juvenile male S. beldingi over 3 consecutive
      years, one of which had a substantially delayed juvenile active season due to
      heavy spring snowfall. We evaluated body fat using the non-destructive method of
      measuring electrical conductivity of the body. When the active season began late,
      acquisition of body mass and body fat were accelerated, and dispersal behaviour
      was inhibited. These results suggest that the ontogeny of mass and fat gain in
      juvenile male S. beldingi is influenced by a seasonal time-keeping mechanism.
      Energy allocation was hierarchical in S. beldingi, with pre-hibernation fattening
      taking precedence over dispersal. Physiological signals reflecting body fat
      content appear to interact with an endogenous timing mechanism in this species to
      regulate the dispersal behaviour of juvenile males.?C 1998 The Association for
      the Study of Animal Behaviour Copyright 1998 The Association for the Study of
      Animal Behaviour Copyright 1998 The Association for the Study of Animal
      Behaviour.

PMID- 9515051
TI  - Behavioural suppression of female pine voles after replacement of the breeding
      male
AB  - Examination of the mechanism of reproductive suppression includes determining
      which cues are involved and the context in which they occur. We studied groups of
      pine voles, Microtus pinetorum, that were disrupted by the replacement of the
      breeding male and compared them with intact family groups. If reproductive
      suppression is mediated by chemical cues, then soiled bedding should be
      sufficient to prevent production of litters by daughters. If reproductive
      suppression involves a behavioural component, we should observe aggressive
      behaviours or those indicative of dominance interactions directed from the mother
      towards the daughter or the replacement male. If replacement of the breeding male
      leads to conflict between the breeding female and her daughter, then more
      aggression or dominance interactions would be expected in disrupted than in
      intact families. The presence of the mother decreased reproduction by daughters,
      but chemical cues alone were not sufficient to prevent the daughter from mating
      with the replacement male. Rather, this decrease in reproduction seemed to be
      mediated by behavioural interactions. We propose that the mother's tugging on the
      daughter may lead to subordination of the daughter. The mother's presence may
      also alter the behaviour patterns of the male and daughter, which could delay
      reproductive activation of the daughter, prevent the formation of pair bonds or
      inhibit sexual behaviour. These behavioural interactions appear to depend on the
      presence of an unfamiliar male, because tugging, for example, was less frequent
      in intact family groups. Copyright 1998 The Association for the Study of Animal
      Behaviour Copyright 1998 The Association for the Study of Animal Behaviour.

PMID- 9515052
TI  - Shift in investment between sexually selected traits: tarnishing of the silver
      spoon
AB  - Studies of resource allocation strategies have concentrated on the influence of
      natural selection on the evolution of life history traits. To a lesser degree,
      the effects of trade-offs between natural and sexual selection on the evolution
      of allocation strategies have also been considered. Trade-offs between sexually
      selected traits that are important to females but that appear to differ in cost,
      however, have not been considered. Female green swordtails, Xiphophorus helleri,
      prefer males with longer swords to males with shorter swords, and in this study
      they demonstrated a preference for larger males to smaller males. Furthermore,
      sexually mature males invested differentially in body and sword growth depending
      on resource availability; males that had an unlimited amount of food invested in
      both body and sword growth, but males shifted to a food-restricted regime halted
      investment in body growth and invested only in sword growth. These results
      suggest that males shift their pattern of investment in two sexually selected
      traits when food becomes restricted. In general, variable environmental
      conditions may favour such conditional investment strategies in species in which
      there is more than one preferred male trait and the costs of the traits differ.
      Copyright 1998 The Association for the Study of Animal Behaviour Copyright 1998
      The Association for the Study of Animal Behaviour.

PMID- 9515053
TI  - Two cooperatively social populations of the theridiid spider Anelosimus studiosus
      in a temperate region
AB  - Social spiders are typically found only in the tropics. In laboratory tests and
      field observations, adult female A. studiosus in two populations in Tennessee,
      U.S.A., a temperate region, showed inter-attraction (grouping behaviour caused by
      the presence of conspecifics), greater tolerance towards conspecifics, and
      cooperation during prey capture and brood care. These are the three classical
      conditions considered typical of social spiders. The populations also had female
      biased sex ratios and limited dispersal. Anelosimus studiosus can thus be
      regarded as a quasi-social or cooperative spider species. These populations of A.
      studiosus are the first social spiders to be described from typically temperate
      regions. Copyright 1998 The Association for the Study of Animal Behaviour
      Copyright 1998 The Association for the Study of Animal Behaviour.

PMID- 9515054
TI  - Membrane topology of NADPH-cytochrome P450 reductase on the endoplasmic
      reticulum.
AB  - Topology of the membrane-anchoring segment of mouse NADPH-cytochrome P450
      reductase in the endoplasmic reticulum membrane was elucidated. An N
      glycosylation site was generated in the amino-terminal hydrophilic sequence of
      the reductase, and the mutated protein was expressed in a cell-free system in the
      presence of microsomal vesicles. The in vitro synthesized reductase protein was
      integrated into the microsomal membrane and N-glycosylated depending on the
      presence of signal recognition particles. We conclude that the amino-terminal
      membrane-anchoring segment of the reductase is a type I signal-anchor sequence
      which shows amino-terminus-lumen and carboxy-terminus-cytoplasm topology.

PMID- 9515055
TI  - The aggregation in human lens proteins blocks the scavenging of UVA-generated
      singlet oxygen by ascorbic acid and glutathione.
AB  - One hour of UVA irradiation of air-saturated solutions of 2 mg/mL solubilized
      lens protein aggregates from aged human lens is able to produce on accumulated
      concentration of more than 2mM 1O2, along with oxidation of 120 nmol/mL of both
      Trp and His amino acid residues. Increasing concentrations of either sodium azide
      or ascorbic acid (up to 10 mM) during the irradiation decreased th His
      destruction by no more than 50-60% with the intact aggregates, but completely
      prevented the His loss with proteolyzed aggregates. Glutathione (up to 10 mM) was
      able to protect less than 10% of the aggregate His residues from oxidative
      damage, whereas His loss was almost completely prevented in the proteolyzed
      aggregates. Similar data were obtained for teh UVA photolysis of the Trp
      residues. This finding led us to study the role a protein conformation of these
      aggregates plays in the diminishing of antioxidant ability to prevent UVA
      mediated photolysis of 1O2-sensitive amino acid residues. We found that Trp, His,
      and Cys are buried in the aggregates and cannot be oxidized by a relatively high
      concentration of 1O2 generated externally to the protein. Increasing urea
      denaturation of the aggregates caused exposure of the buried Trp residues as
      determined by the red shift of the fluorescence maximum and by a marked increase
      in the acrylamide and iodide fluorescence quenching. The ability of glutathione
      to prevent Trp oxidation by UVA light correlated directly with the extent of Trp
      exposure. These data suggest that the aggregation of the lens crystallins during
      aging produces a barrier, which prevents the access of water-soluble antioxidants
      to the sites of UVA-dependent singlet oxygen generation. In this case UVA
      proteolysis of the lens proteins can proceed even in the presence of
      physiological levels of antioxidants.

PMID- 9515056
TI  - UVA irradiation of human lens proteins produces residual oxidation of ascorbic
      acid even in the presence of high levels of glutathione.
AB  - The oxidation products of ascorbic acid (AscH-) can rapidly glycate and crosslink
      lens proteins in vitro, producing fluorophores and browning products similar to
      those present in cataractous lenses. The accumulation of AscH- oxidation
      products, however, would largely be prevented by the millimolar levels of
      glutathione (GSH) present in human lens. Here we investigate whether protein
      aggregation could allow the oxidation of AscH- by UVA-induced reactive oxygen
      species in the presence of physiological levels of GSH. The metal-catalyzed
      oxidation of 1.0 mM AscH- by 50 microM Cu(II) was almost complete after 1 h, but
      no oxidation was seen in the presence of GSH concentrations as low as 0.5 mM. UVA
      irradiation of protein aggregates from human lens, which accumulated more than
      2.0 mM singlet oxygen after 1 h, caused a 50-60% oxidation of 1.0 mM AscH-. The
      addition of 204 mM GSH, however, decreased AscH- oxidation by less than half, and
      30% of the AscH- was oxidized even in the presence of 15 mM GSH. This diminished
      protection may be due, in part, to the ability of AscH-, but not GSH, to
      penetrate to the sites of singlet oxygen generation located within the protein.
      Consistent with this hypothesis, greater GSH protection was seen when a
      proteolytic digest of the human proteins was subjected to the same irradiation or
      when singlet oxygen was chemically generated from 3-(4-methyl-1
      naphthyl)propionic acid endoperoxide (MNPAE) at 37 degrees C in the medium. The
      addition of 50 microM Cu(II) had no effect on the rate of degradation of
      dehydroascorbic acid (DHA). Singlet oxygen, either UVA- or MNPAE-generated,
      increased the rate of DHA loss. This secondary oxidation of DHA by singlet oxygen
      would allow the accumulation of AscH- oxidation products was not reducible by
      GSH. Therefore, the data presented here argue that the protein aggregation seen
      in older human lenses may permit oxidized AscH--induced crosslinking to occur
      even at physiological GSH levels.

PMID- 9515057
TI  - Mechanical properties of the collagen network in human articular cartilage as
      measured by osmotic stress technique.
AB  - We have used an isotropic osmotic stress technique to assess the swelling
      pressures of human articular cartilage over a wide range of hydrations in order
      to determine from these measurements, for the first time, the tensile stress in
      the collagen network, Pc, as a function of hydration. Osmotic stress was applied
      by means of calibrated solutions of polyethylene glycol. Calculations of osmotic
      stress were based on the balance, at equilibrium, between the applied stress, the
      collagen stress, and the proteoglycan osmotic pressure, piPG, acting within the
      extrafibrillar matrix compartment. Pc vs hydration was determined for several
      normal human samples, both native and trypsin-treated, and for cartilage from one
      osteoarthritic (OA) joint. We found that for normal cartilage the collagen
      network does not become "limp" until the volume of cartilage has decreased by 20
      25% of its initial value and that its contribution to the balance of forces in
      cartilage therefore must be taken into account over a much wider range of
      hydrations than was previously thought. For normal cartilage, the Pc vs hydration
      curves exhibit a steep increase with increasing hydration; trypsin treatment does
      not change their slope, showing that PG concentration does not influence the
      inherent stiffness of the collagen network. By contrast, the curves for OA
      specimens are considerably shallower and displaced to higher hydrations. Our
      findings thus highlight the role of the stiffness of the collagen network in
      limiting hydration in normal cartilage and ensuring a high PG concentration in
      the matrix, which is essential for effective load-bearing and is lost in OA.

PMID- 9515058
TI  - Role of individual N-linked glycosylation sites in the function and intracellular
      transport of the human alpha folate receptor.
AB  - Glycosylation is a structural feature of all three isoforms of the human folate
      receptor. We have used site-directed mutagenesis to study the role of individual
      glycosylation sites in the assembly and function of the a isoform of the human
      folate receptor (alpha(h)FR). Three potential N-linked glycosylation sites in the
      alpha(h)FR sequence were disrupted by conservative mutation of the S or T
      residues in the consensus sequence (N-X-S/T) to A or V, respectively. Constructs
      with the single mutations S(71)-->A (alpha(h)FR(-1)), T(163)-->V (alpha(h)FR(
      2)), and S(203)-->A (alpha(h)FR(-3)); the double mutation S(71)--> A/S(203)-->A
      (alpha(h)FR(-1-3)); and the triple mutation S(71)--> A/S(203)--> A/T(163)--> V
      (alpha(h)FR(-1-2-3)) were stably transfected into Chinese hamster ovary (CHO)
      cells. The proteins produced in CHO cells by the mutated cDNAs have apparent
      molecular weights that are reduced relative to the wild type and are consistent
      with the loss of carbohydrate residues. The triple mutant, which lacks all three
      consensus glycosylation sites, yields protein that comigrates with the
      enzymatically deglycosylated native protein. Determinations of the K(D) for folic
      acid by Scatchard analyses of the glycosylation mutants indicate that folic acid
      binding affinity is not significantly affected in the single mutants alpha(h)FR(
      1) and alpha(h)FR(-2). However, in the single mutant, alpha(h)FR(-3), and the
      double mutant, alpha(h)FR(-1-3), folic acid binding affinity is respectively 2.7-
      and 3.5-fold lower than that in wild type. Deglycosylation by mutation of all
      three consensus sites (alpha(h)FR(-1-2-3) eliminates both folic acid binding and
      cell surface expression. In contrast, enzymatic deglycosylation of purified wild
      type alpha(h)FR with endoglycosidase F does not significantly affect folate
      binding affinity. Thus, while carbohydrate residues are not essential for the
      folate binding activity of the mature folate receptor, at least one of the three
      core glycosylated residues is necessary for the synthesis of alpha(h)FR in its
      active conformation.

PMID- 9515059
TI  - Oligomeric protein structure of beef spleen exonuclease.
AB  - A one-step purification of beef spleen exonuclease in the form of a DNA-enzyme
      complex is described. The purity of the exonuclease was verified by two
      dimensional gel electrophoresis. It possesses molecular mass 160 kDa and pI 6.92.
      The one-dimensional sodium dodecyl sulfate gel after reduction with beta
      mercaptoethanol suggests that the 160-kDa exonuclease consists of four
      polypeptide chains of two different types with molecular masses 55 and 25 kDa.
      The tetrameric structure of the exonuclease is supported by intermolecular
      disulfide bonds, and their partial reduction leads to the formation of one stable
      intermediate with molecular mass 80 kDa formed by binding one 55-kDa with one 25
      kDa subunit into a dimer. During two-dimensional gel electrophoresis, the dimer
      showed pI 6.92 while monomers showed pI 6.78 for the 55-kDa and pI 6.29 for the
      25-kDa. Two other intermediate states of two big and one small (135 kDa) and two
      small and one big subunit (105 kDa) were also visualized. They are unstable and
      easily dissociated into one 80-kDa dimer and either one 55-kDa or one 25-kDa
      monomer. The immunoblotting analysis with specific polyclonal antibodies against
      160-kDa protein confirmed the subunit structure of the exonuclease. It was found
      that both monomers are glycosylated.

PMID- 9515060
TI  - INTERLEUKIN 12 AND B7/CD28 INTERACTION SYNERGISTICALLY UPREGULATE INTERLEUKIN 10
      PRODUCTION BY HUMAN T CELLS

PMID- 9515061
TI  - Emergency room visits for respiratory illnesses among the elderly in Montreal:
      association with low level ozone exposure.
AB  - Population-based studies of hospital usage have been used to identify the ongoing
      adverse impacts of photochemical air pollutants on respiratory health. In this
      study we examined the relationship between the number of daily emergency room
      (ER) visits for respiratory illnesses (25 hospitals) and outdoor air pollution in
      Montreal, Quebec (June-August, 1989-1990). Air pollutants measured included 1-
      and 8-h maximum ozone (O3) and estimated particulate matter < 2.5 microns in
      aerometric diameter (PM2.5). Seasonal and day-of-week trends, autocorrelation,
      temperature, and relative humidity were controlled for in-time series
      regressions. Although O3 levels never exceeded the U.S. National Ambient Air
      Quality Standard (NAAQS) of 120 ppb (maximum day, 106 ppb), statistically
      significant (P < 0.01) relationships were found between respiratory ER visits for
      patients over the age of 64 and both 1- and 8-h maximum O3 measured 1 day prior
      to the ER visit day during the 1989 summer: ER visits were 18.7% higher than
      average (95% Cl, 6.5-30.9%) for a mean increase of 44 ppb O3 (1-h maximum), and
      21.8% higher than average (95% Cl, 9.7-33.8%) for a mean increase of 38 ppb O3 (8
      h maximum). There was an association between respiratory ER visits for the
      elderly and estimated PM2.5 lagged 1 day (0.1 visit/microgram/m3 PM2.5, P <
      0.07), but this was confounded by both temperature and O3. The only finding for a
      reference group of nonrespiratory conditions was an inverse association between
      ER visits for infants and O3, but this was confounded by weather. These findings
      confirm the impression that while air quality standards may protect the
      respiratory health of the general population, this is not the case for
      susceptible subgroups such as the elderly.

PMID- 9515062
TI  - Lung cancer risk and workplace exposures in black men and women.
AB  - There are little data on workplace exposures and lung cancer risk in blacks. An
      ongoing case-control study of lung cancer that included 550 black men and women
      with lung cancer and 386 age-matched controls was examined by reported
      occupational exposures and job titles. In men, significant associations were
      observed with reported exposure to asbestos [odds ratio (OR), 1.8; 95% confidence
      intervals (CI) 1.03-3.1] and coal dust (OR, 2.8; 95% CI 1.1-7.0). Elevated but
      nonsignificant risks of 1.4 or more were detected for the following occupations:
      police/security guards, farmers/farm workers, laborers, and motor-vehicle
      drivers. In women, nonsignificant increased risks were found with reported
      exposure to paint (OR, 1.8) and gas fumes (OR, 4.9). Women employed as
      farmers/farm workers and building maintenance workers had elevated but
      nonsignificant risks.

PMID- 9515063
TI  - The relationship between symptoms and IgG and IgE antibodies in an office
      environment.
AB  - Airborne fungi have been postulated as a cause of symptoms among office workers.
      Using the MAST chemiluminescent system, this study evaluated 36 IgG and 36 IgE
      antibody levels in 47 office workers from an area with elevated airborne fungal
      concentrations and 44 office workers from an otherwise similar area with lower
      airborne fungal exposure. No difference was found in IgG antibody to fungi
      between the lower and higher exposure areas, but high IgG antibody to one or more
      of the fungi studied was detected in 67% of all the workers tested. IgE antibody
      to one or more antigens was detected in 40% of the participants. Workers who
      reported atopic symptoms (sneezing, runny nose, and itchy eyes) or "sick
      building" symptoms (any three of the following temporally related to work:
      headache, fatigue, stuffy nose, irritated eyes, or sore throat) were more likely
      to have one positive IgE antibody test. Type I hypersensitivity to aeroallergens
      besides fungi may play a role in some symptoms reported by some participants in
      this office building.

PMID- 9515064
TI  - Assessing the health benefits of reducing particulate matter air pollution in the
      United States.
AB  - Most Americans are exposed daily to airborne particulate matter (PM), a pollutant
      regulated by the U.S. Environmental Protection Agency. Current national standards
      are set for PM10 (particles less than 10 microns in diameter) and new standards
      have been promulgated for PM2.5 (particles less than 2.5 microns in diameter).
      Both particle sizes have been associated with mortality and morbidity in studies
      in the United States and elsewhere and an unambiguously safe level of ambient PM
      has been difficult to identify. PM10 concentrations have been reduced
      significantly in U.S. cities over the past two decades and relatively few
      locations continue to exceed national PM10 standards. However, the new PM2.5
      standards will require further reductions in PM concentrations and additional
      expenditures for emission controls. Information about the health and economic
      benefits of achieving lower PM concentrations is important because: (1) expected
      costs of further PM reductions rise after the least-cost options are exhausted,
      and (2) there is uncertainty about the existence of a threshold safe level for
      PM. This paper develops and applies a methodology for quantifying the health
      benefits of potential reductions in ambient PM. Although uncertainties exist
      about several components of the methodology, the results indicate that the annual
      nationwide health benefits of achieving the new standards for PM2.5 relative to
      1994-1996 ambient concentrations are likely to be between $14 billion and $55
      billion annually, with a mean estimate of $32 billion.

PMID- 9515065
TI  - Lead-induced hypertension. II. Response to sequential infusions of L-arginine,
      superoxide dismutase, and nitroprusside.
AB  - Administration of 100 ppm lead acetate daily for 3 months caused hypertension in
      Sprague-Dawley rats, with reversal by treatment with 2,3-dimercaptosuccinic acid
      (DMSA) (0.5% for 2 weeks). Animals from each group were infused sequentially in
      30-min intervals with saline (S), L-arginine (Arg), Arg+ superoxide dismutase
      (SOD), S, and sodium nitroprusside (SNP). Baseline mean blood pressure (MBP) was
      elevated in lead-treated animals (Pb) compared to that in controls(C), returning
      toward normal after DMSA (105 +/- 2 mmHg, C, vs 149 +/- 2, Pb, and 124 +/- 1,
      DMSA, P < 0.001). Infusion of Arg caused a fall in MBP in all animals,
      normalizing the MBP in Pb-treated animals. SNP caused a greater fall in MBP in
      all groups of animals, normalizing the MBP in Pb. Measurement of urinary nitrite
      + nitrate (NOx) by chemiluminescence revealed at baseline a reduced level in Pb,
      restored to normal by DMSA (6.6 +/- 1.5 nmol/min/100 g BW, C, vs 3.3 +/- 1.7, Pb,
      P < 0.05, vs 5.8 +/- 2.6, DMSA, P = NS). Infusion of arginine increased urinary
      NOx in all groups, but to a lesser degree in Pb and DMSA. Assay of plasma
      malondialdehyde (MDA) by HPLC, as a measure of reactive oxygen species (ROS), was
      elevated at baseline in Pb, reduced by DMSA (3.6 +/- 0.4 mumol/L, Pb, vs 1.9 +/-
      0.2, C, and 1.9 +/- 0.3, DMSA, P < 0.01). In the Pb group, SOD resulted in a
      significant fall in MDA (2.0 +/- 0.3 mumol/L, SOD, vs 3.1 +/- 0.1, Arg, P <
      0.01), but no further fall in MBP or increase in urinary NOx. Thus, hypertension
      in lead-exposed animals is related to both diminished NO and increased ROS. The
      elevation in MBP can be ameliorated by additional NO through infusion of
      substrate arginine or by treatment with the ROS scavenger, DMSA. Lead-exposed
      animals show enhanced MBP sensitivity to the NO donors, Arg and SNP, but no
      further response to SOD, despite a reduction in MDA to normal. We speculate that
      lead-induced hypertension may be caused by one species of ROS which enhances
      vascular reactivity, and that provision of additional NO acts to scavenge the ROS
      and/or acts directly as a vasodilator.

PMID- 9515066
TI  - Incidence of heavy metal contamination in water supplies in northern Mexico.
AB  - Contaminants in drinking water present public health risks. The objective of this
      study was to analyze water samples taken from wells or storage tanks, direct
      sources for domestic water in Northern Mexico, for the presence of lead (Pb),
      copper (Cu), cadmium (Cd), arsenic (As), and mercury (Hg). The samples were
      analyzed by atomic absorption coupled with a hydride generator or a graphite
      furnace. High levels of Pb (0.05-0.12 ppm) were found in Hermosillo, Guaymas, and
      Nacozari. Forty-three percent of the samples in Sonora exceeded the action level
      (0.015 ppm) established by the EPA for Pb. For As, 8.92% exceeded the limit with
      a range of 0.002-0.305 ppm. Several studies have indicated a possible link
      between As and fluoride (F) in drinking water. This study showed a positive
      correlation between F and As (r = 0.53, P = 0.01, and n = 116). One location in
      Hermosillo had 7.36 ppm of F and 0.117 ppm of As, 3.5 times the recommended F
      levels in drinking water and 2 times higher than the level permitted for As. Hg
      contamination was found in 42% of the samples. Based on the results of this
      study, it appears that As, Hg, and Pb contamination in the drinking water for
      some areas of the state of Sonora is a major concern.

PMID- 9515067
TI  - Environmental exposures to lead and urban children's blood lead levels.
AB  - Lead-contaminated water, soil, and paint have been recognized as potential
      sources of children's lead exposure for decades, but their contributions to lead
      intake among urban children remain poorly defined. This analysis was undertaken
      to estimate the relationship of environmental lead exposures to lead intake among
      a random sample of urban children, adjusted for exposure to lead-contaminated
      house dust. Analyses of 183 urban children enrolled in a random sample, cross
      sectional study were conducted. Children's blood and multiple measures of
      household dust, water, soil, and paint were analyzed for lead, and interviews
      were conducted to ascertain risk factors for childhood lead exposure.
      Environmental sources of lead, including house-dust, soil lead, and water lead,
      were independently associated with children's blood lead levels. In contrast,
      paint lead levels did not have a significant effect on blood lead levels after
      adjusting for other environmental exposures. An increase in water lead
      concentration from background levels to 0.015 mg/L, the current EPA water lead
      standard, was associated with an increase of 13.7% in the percentage of children
      estimated to have a blood lead concentration exceeding 10 micrograms/dL;
      increasing soil lead concentration from background to 400 micrograms/g was
      estimated to produce an increase of 11.6% in the percentage of children estimated
      to have a blood lead level exceeding 10 micrograms/dL, and increasing dust lead
      loading from background to 200 micrograms/ft2 is estimated to produce an increase
      of 23.3% in the percentage of children estimated to have a blood lead level
      exceeding 10 micrograms/dL. These data support the promulgation of health-based
      standards for lead-contaminated dust and soil and the progressive lowering of
      standards for lead-contaminated water as the definition of undue lead exposure
      has been modified.

PMID- 9515068
TI  - Dietary exposure to chemical contaminants from traditional food among adult
      Dene/Metis in the western Northwest Territories, Canada.
AB  - Environmental contaminants such as organochlorines and heavy metals have been
      reported to bioaccumulate in Arctic and subarctic wildlife. The Indigenous
      Peoples in northern and Arctic Canada rely on local wildlife as an important food
      source, and it is thus hypothesized that they may have high intakes of these
      contaminants. Herein, an assessment of dietary exposure to selected
      organochlorines and heavy metals for Indigenous Peoples of the western Northwest
      Territories (NWT) is presented. Dietary data were collected from 1012 adults with
      24-h recalls in 16 communities in the western NWT (Denendeh). A comprehensive
      survey of the literature, as well as in-house analysis, formed the basis of a
      large traditional food-contaminant database. By combining the dietary and
      contaminant data, dietary exposure to 11 chemical contaminants was calculated.
      Dietary exposure to chemical contaminants in Denendeh is generally low and there
      is little, if any, associated health risk. However there are specific
      contaminants in certain communities for which exposure on a single day approaches
      the tolerable daily intake levels. These situations are detailed and monitoring
      needs are described.

PMID- 9515069
TI  - A position paper on selenium in ecotoxicology: a procedure for deriving site
      specific water quality criteria.
AB  - This paper describes a method for deriving site-specific water quality criteria
      for selenium using a two-step process: (1) gather information on selenium
      residues and biological effects at the site and in down-gradient systems and (2)
      examine criteria based on the degree of bioaccumulation, the relationship between
      measured residues and threshold concentrations for reproductive effects in fish
      and wildlife, and any observed reproductive impacts. Several outcomes are
      possible--criteria can be left unmodified, adjusted upward by a fixed amount
      (50%), or adjusted downward by one of three amounts (25, 50, or 75%). A criterion
      (existing or proposed) is lowered or raised by an amount that is proportional to
      the magnitude of bioaccumulation and toxic effects present--i.e., the degree of
      biological hazard. Criteria can be modified under two circumstances: (1)
      diagnostic residues and toxic effects must be coupled (present) in order to lower
      a criterion or (2) diagnostic residues and toxic effects must be coupled (absent)
      in order to raise a criterion. Coupling residues and effects makes the procedure
      sensitive to the natural inter- and intraspecific variation in bioaccumulation
      and toxic responses exhibited by fish and wildlife in aquatic ecosystems. The
      goal is to establish criteria that keep food-chain bioaccumulation below levels
      that result in toxicity to fish and wildlife. Precautions are given for those
      attempting to apply the generic EPA model for implementing national water quality
      criteria to a site-specific selenium criterion.

PMID- 9515070
TI  - Short-term toxicity of lindane, hexachlorobenzene, and copper sulfate to
      tubificid sludgeworms (Oligochaeta) in artificial media.
AB  - The toxicity of lindane, hexachlorobenzene, and copper sulfate to Tubifex tubifex
      and Limnodrilus hoffmeisteri was determined using an easily applicable and
      standardizable 72-h short-term test system. It was designed for the quick
      assessment of sublethal and lethal effects of sediment-associated chemicals on
      the worms. An artificial sediment based on the Artificial Soil according to OECD
      Guideline No. 207 was used as test medium. The data confirm the common view that
      oligochaetes are highly tolerant of lethal effects. However, sublethal effects
      were detected at considerably lower concentrations than found for lethal effects.
      The EC50 values for autotomy (172 mg/kg dry wt sediment) and sediment avoidance
      (217 mg/kg) for T. tubifex exposed to lindane-contaminated sediment were, for
      example, more than five times lower than the LC50 value (> 1000 mg/kg). The no
      observed-effect concentration for reworking activity (8 mg/kg) was more than 125
      times lower than the LC50. Tubificids thus turned out to represent useful test
      organisms for the assessment of the ecotoxicological hazard potential of
      chemicals in the sediment compartment, because the sublethal effects not only
      affect the individual, but can influence the population levels and, consequently,
      the composition of the benthic community.

PMID- 9515071
TI  - Cadmium uptake and bioaccumulation in Xenopus laevis embryos at different
      developmental stages.
AB  - The uptake of cadmium in Xenopus laevis embryos was studied by exposing them to
      solutions containing cadmium concentrations ranging from 0.1 to 2 mg Cd2+/L at
      seven developmental stages for 72 h. The uptake values were from 0.0027 microgram
      Cd2+/embryo (two blastomeres stage) to 0.081 microgram Cd2+/embryo, (hindlimb bud
      distinct stage). During early developmental stages, a limited permeability to
      cadmium could play a significant role for the survival of embryos. At the last
      developmental stage evaluated there was a significantly higher uptake of cadmium
      simultaneously with a very significant increase in the resistance against cadmium
      toxicity. The cadmium bioaccumulation factor (BF) ranged from 5 to 460. As a
      general pattern at all developmental stages the BF was higher in embryos exposed
      to the lower cadmium concentration, and as development advanced the BF increased.

PMID- 9515072
TI  - Toxic peripheral neuropathy of chicks fed Senna occidentalis seeds.
AB  - Plants of the genus Senna (formerly Cassia) are poisonous to livestock and other
      laboratory animals, leading to a syndrome of a widespread muscle degeneration,
      incoordination, recumbence, and death. The main histologic lesion is necrosis of
      skeletal muscle fibers. Recently, a mitochondrial myopathy with ragged-red and
      cytochrome oxidase (COX)-negative muscle fibers was recognized in hens
      chronically intoxicated with parts of seeds of S. occidentalis. The purpose of
      the present work was to investigate if there was peripheral nerve involvement in
      the acute intoxication of chicks with S. occidentalis seeds. Teasing of
      individual fibers revealed signs of extensive axonal damage with myelin ovoids.
      Ultrathin sections confirmed the axonal damage. Axons were filled with membranes,
      some residual disorganized filaments, and enlarged mitochondria. In some
      instances the axon disappeared and there was secondary degeneration of the myelin
      sheath. The present work is the first description of the neurotoxic effect of S.
      occidentalis intoxication. Future work should attempt to determine the mechanisms
      involved in this neuropathy.

PMID- 9515073
TI  - Procedure to screen illicit discharge of toxic substances in septic sludge
      received at a wastewater treatment plant.
AB  - This paper presents an integrative approach, using toxicological and chemical
      analyses, to screen toxic and illegal substances that could be added to the
      septic sludge transported by a tanker truck to the wastewater treatment plant of
      the Montreal Urban Community (MUC). Microtox, lettuce root elongation, and a
      bacterial respiration test were used to establish the toxicity range of a normal
      sludge and the determination of threshold limit criteria. Septic sludge samples
      were spiked with different types and amounts of contaminants (copper, zinc,
      phenol, industrial sludge). Conservative criteria were applied to detect abnormal
      toxicity with great reliability while avoiding false positives (i.e., detecting
      abnormal toxicity in nonspiked sludge). Taken individually, toxicity tests using
      Microtox were revealed to be the least discriminating toxicological method
      (efficiency of 45% when the ratio of the IC50 values is considered), whereas
      lettuce root elongation was relatively the most efficient (80% of spiked
      samples). As a whole, the battery of toxicity tests detected at least 93% of the
      spiked sludge samples. This procedure is also very efficient, i.e., easy to
      apply, cost effective, and rapid. In certain cases, an abnormal toxicity level
      can be determined within a few hours, whereas a septic sludge can be classified
      as normal within 5 days.

PMID- 9515074
TI  - Effect of heavy metals on Aedes aegypti (Diptera: Culicidae) larvae.
AB  - Studies were conducted to determine the biological effects of heavy metals on the
      development of Aedes aegypti. Embryos immersed in 32 ppm Cu or 5 ppm Cd did not
      hatch. The arrest of hatching was in part reversible by removal of the heavy
      metals. The mortality rate of third-instar larvae exposed to heavy metals for 24
      h was metal and dose dependent; the 50% lethal concentration (LC50) endpoints
      were 3.1, 16.5, and 33 ppm for Hg, Cd, and Cu, respectively. Interestingly, a
      proportion of Aedes aegypti third-instar larvae exposed to either Cu or Cd for 24
      h failed to produce a dissectable peritrophic matrix. This failure to produce a
      dissectable peritrophic matrix also was metal and dose dependent. These results
      are discussed in the context of Aedes aegypti as a model system for investigating
      the molecular biological effects of heavy metals in aquatic insects.

PMID- 9515075
TI  - Microbial toxicity in soil medium.
AB  - A laboratory procedure using the respirometer was developed to measure microbial
      toxicity in soils of organic chemicals. The procedure was tested with Polytox, a
      commercial microbial test culture, on 35 organic chemicals. The test protocol was
      reproducible with a mean standard deviation of 0.08 mg chemical/g of soil for
      eight chemicals. The assays were also carried out at different moisture-holding
      capacities of soil. Correlation between toxicity tests done in aqueous medium and
      soil for Polytox test culture was statistically significant and yielded an r2 of
      0.816. Details of the laboratory procedure and test results are presented
      together with comparisons of toxicity of chemicals in the soil medium with that
      in aqueous medium for the same test organism. A few practical applications are
      discussed.

PMID- 9515076
TI  - Amelioration of the photo-induced toxicity of polycyclic aromatic hydrocarbons by
      a commercial humic acid.
AB  - The ability of a commercial (Aldrich Chemical Co.) humic acid (AHA) to ameliorate
      the photo-induced toxicity of polycyclic aromatic hydrocarbons (PAHs) was
      examined using Lemna gibba L. (G3). Plants were exposed to anthracene and
      benzo(a)pyrene both with and without AHA and grown under visible light as well as
      lighting that simulates relative abundances of UV-A and UV-B in natural sunlight
      (SSR). Modest additions of 1.6 mg.L-1 AHA were sufficient to ameliorate the photo
      induced toxicity of 2 mg.L-1 anthracene by improving growth rates to nearly 50%
      of controls and inducing minor recovery from complete chlorosis in the most
      highly affected plants. Benzo(a)pyrene induced minor, but significant, chlorosis
      under SSR, and AHA additions always increased growth rate and chlorophyll
      content, although to less of a degree than anthracene toxicity under SSR. The
      protective effects of AHA on anthracene toxicity increased linearly with
      increases in AHA concentrations up to 6.2 mg.L-1. Slopes of these relationships
      changed in the presence of UV light relative to visible light treatments; thus UV
      changed the extent to which AHA mediates PAH toxicity. However, the net effect
      was still for AHA to ameliorate PAH photo-induced toxicity even though UV has the
      potential to photooxidize AHA and enhance the production of potentially toxic
      reactive oxygen species from AHA photosensitization.

PMID- 9515078
TI  - EDITORIAL
AB  - Copyright

PMID- 9515077
TI  - Structure-toxicity relationships for three mechanisms of action of toxicity to
      Vibrio fischeri.
AB  - Quantitative structure-activity relationships (QSARs) have been developed with
      the logarithm of the inverse of 15-min toxicity (pT15) to Vibrio fischeri (the
      acute Microtox test). Statistically, robust QSARs were found for alkanones acting
      by the nonreactive, baseline narcosis mechanism of action [pT15 = 0.99 (log Kow)
      2.08, n = 6, s = 0.24, r2 = 0.988, F = 405]; aldehydes acting by the Schiff base
      forming mechanism of electrophilicity [pT15 = 0.55(log Kow)-0.58, n = 6, s =
      0.07, r2 = 0.994, F = 782]; and alkenals acting by the Michael-type acceptor
      mechanism of electrophilicity [pT15 = 0.52(log Kow) + 0.35, n = 6, s = 0.19, r2 =
      0.914, F = 54.5]. Efforts to model toxicity across mechanism of action resulted
      in the development of a response surface [pT15 = 0.79(log Kow)-1.17 (ELUMO)-0.41,
      n = 19, s = 0.46, r2 = 0.892, F = 75.3]. In addition, an excellent correlation
      was found between Tetrahymena pyriformis [log(1/IGC50)] and V. fischeri.
      [log(1/IGC50) = 0.86(pT15)-0.25, n = 19, s = 0.25, r2 = 0.957, F = 405] toxicity.

PMID- 9515080
TI  - Applications of computer-intensive statistical methods to environmental research.
AB  - Conventional statistical approaches rely heavily on the properties of the central
      limit theorem to bridge the gap between the characteristics of a sample and some
      theoretical sampling distribution. Problems associated with nonrandom sampling,
      unknown population distributions, heterogeneous variances, small sample sizes,
      and missing data jeopardize the assumptions of such approaches and cast
      skepticism on conclusions. Conventional nonparametric alternatives offer freedom
      from distribution assumptions, but design limitations and loss of power can be
      serious drawbacks. With the data-processing capacity of today's computers, a new
      dimension of distribution-free statistical methods has evolved that addresses
      many of the limitations of conventional parametric and nonparametric methods.
      Computer-intensive statistical methods involve reshuffling, resampling, or
      simulating a data set thousands of times to empirically define a sampling
      distribution for a chosen test statistic. The only assumption necessary for valid
      results is the random assignment of experimental units to the test groups or
      treatments. Application to a real data set illustrates the advantages of these
      methods, including freedom from distribution assumptions without loss of power,
      complete choice over test statistics, easy adaptation to design complexities and
      missing data, and considerable intuitive appeal. The illustrations also reveal
      that computer-intensive methods can be more time consuming than conventional
      methods and the amount of computer code required to orchestrate reshuffling,
      resampling, or simulation procedures can be appreciable.

PMID- 9515079
TI  - Aquatic toxicity testing of sparingly soluble, volatile, and unstable substances
      and interpretation and use of data. Task Force of the European Centre for
      Ecotoxicology and Toxicology of Chemicals.
AB  - Aquatic toxicity tests were originally designed for individual compounds that are
      soluble and stable in water. For sparingly soluble substances that are not toxic
      at the solubility limit, the issue is whether tests should be performed with
      insoluble test substance present. Based on a literature evaluation of the
      physiology of uptake, it was concluded that only the dissolved fraction is
      available for uptake and that the insoluble test substance may introduce
      artifacts that aggravate data interpretation. Therefore, toxicity tests should be
      conducted only up to the solubility limit. Testing of volatile, unstable, or
      adsorptive substances is complicated by the ability to keep exposure
      concentrations relatively constant. For these, appropriate test protocols
      including adequate design of the dosing systems must be employed. For test medium
      preparation, physical methods and, where necessary, use of low concentrations of
      certain solvents are recommended to support handling and speed of dissolution.
      However, recommendation is made against the use of dispersants. Water
      accommodated fractions are recommended as one approach for dosing multicomponent
      substances. Interpretation of observed effects depends on appropriate test medium
      preparation, correct measurement and expression of exposure levels, and
      differentiation of true toxicity from indirect physical effects of the substance,
      or the toxicity of impurities.

PMID- 9515081
TI  - Trifluralin transfer from top soil.
AB  - Leaching of 14C-ring-labeled technical trifluralin from the top 5 cm of soil was
      followed in a microlysimeter experiment under outdoor conditions. Leaching of
      water residues from soil was low and represented 2.2, 5.4, and 6.7% of the
      applied radioactivity after 6, 12, and 18 months, respectively. Two degradation
      products, called A and B, were clearly detected and represented about 80 and 10%
      of the leached radioactivity, respectively, whereas other degradation products
      accounted for about 10%. Trifluralin itself was detected in the leachate only
      between 3 and 6 months. Cumulated amounts of leached trifluralin were only 1% of
      the leached radioactivity after 1 year: i.e., 0.06% of the applied product. A
      second-year microlysimeter experiment demonstrated that the use of formulated
      trifluralin had no influence on leached amount and content.

PMID- 9515082
TI  - Altered metabolic elimination of testosterone and associated toxicity following
      exposure of Daphnia magna to nonylphenol polyethoxylate.
AB  - The ability of nonylphenol polyethoxylate (nonylphenyl polyethylene glycol, NPPG)
      to alter the metabolic elimination of testosterone and elicit reproductive
      toxicity to Daphnia magna was assessed. NPPG (5.0 mg/liter) inhibited the
      elimination of testosterone as glucose and sulfate conjugates, but had minimal
      effect on the rate of elimination of oxido-reduced and hydroxylated derivatives
      of the steroid hormone. This exposure concentration of NPPG also approximated the
      acute threshold-effect concentration and the chronic value for daphnids. Results
      demonstrated that NPPG qualitatively elicits similar effects on the metabolic
      elimination of testosterone by daphnids as previously characterized with its
      degradation product 4-nonylphenol. Unlike 4-nonylphenol, significant chronic
      toxicity of NPPG, due to effects on steroid elimination processes, was not
      evident. Results from the present study provide no indication that concentrations
      of nonylphenol polyethoxylates typically measured in the environment pose a risk
      of chronic toxicity to invertebrates.

PMID- 9515083
TI  - Structure- and property-activity relationship models for prediction of microbial
      toxicity of organic chemicals to activated sludge.
AB  - Two quantitative structure-activity relationship (QSAR) and two quantitative
      property-activity relationship (QPAR) models reported in the literature for
      predicting toxicity of synthetic organic chemicals to activated sludge
      microorganisms are summarized and compared. The QSAR models were developed using
      solvatochromic parameters and molecular connectivity indices; the QPAR models,
      using octanol-water partition coefficient and aqueous solubility. Experimental
      data on 16 chemicals not used in developing the above models are used to compare
      and evaluate the predictive ability of these QSAR/QPAR models. Based on the
      quality of the original models, their predictions, ease of application, and
      availability of model parameters, molecular connectivity indices and log P appear
      to be the most suitable in toxicity predictions.

PMID- 9515084
TI  - Effects of halobenzenes on growth rate of fish (Gambusia affinis).
AB  - The growth rate reduction of mosquito fish (Gambusia affinis) fry was
      investigated with a range of sublethal exposure levels of four halobenzenes for
      42 days. These compounds were found to produce growth rate reduction in mosquito
      fish fry at concentrations as low as 0.30, 0.18, 0.025, and 0.010 mumol liter-1
      for 1,4-dibromobenzene, 1,2,3-trichlorobenzene, 1,2,4-tribomobenzene, and
      pentachlorobenzene, respectively. The aqueous exposure concentrations causing
      growth rate reduction of 50 and 10% (EC50 and EC10, respectively) for the
      halobenzenes were 0.067-3.4 and 0.0042-0.32 mumol liter-1, respectively. The EC50
      and EC10 values are within the ranges of 5 to 8% and 0.1 to 3.9% of the LC50
      values, respectively. The percentage of growth rate reduction relative to the
      LC50 could possibly be used to describe chronic toxicity effects of organic
      compounds with the aquatic organisms. The internal concentrations obtained from
      the analysis for the halobenzenes were generally consistent with the calculated
      internal concentrations. The lipid-based internal concentrations that gave 50 and
      10% growth rate reductions were 8.3-27 and 0.5-1.6 mmol kg-1, respectively. These
      values have a more limited range than the corresponding external aqueous
      concentrations. The quantitative structure-activity relationships between the
      internal concentrations at 50 and 10% growth rate reduction and physicochemical
      parameters were found to be less satisfactory than those based on external
      aqueous concentrations.

PMID- 9515085
TI  - Assessment of the effectiveness of composting for the reduction of toxicity and
      mutagenicity of explosive-contaminated soil.
AB  - Composting is being developed as an economical method for remediating explosive
      contaminated soils and has been found to reduce the concentrations of target
      contaminants such as 2,4,6-trinitrotoluene (TNT) and hexahydro-1,3,5-trinitro
      1,3,5-triazine (RDX). However, whether environmental safety is improved by
      composting can be determined only by assessing the effects of the treated
      material on living organisms. In this study two bioassays, the Mutatox assay and
      the earthworm acute toxicity test, were used to evaluate the effectiveness of a
      pilotscale composting demonstration in reducing environmental hazard. Explosive
      contaminated soil was collected from a military installation and amended for
      composting in two adiabatic reactors. The unamended soil was lethal to all
      exposed earthworms, as were both amended replicates, prior to composting. Serial
      dilutions of the finished composts with artificial soil had earthworm 14-day LC50
      values of 35.7 and 100% finished compost: artificial soil. Extracts of the
      initial materials were also toxic to bacteria in the Mutatox assay. Dilutions of
      those extracts to sublethal concentrations revealed a low level of mutagenicity.
      Extracts of the finished composts indicated reduced bacterial toxicity, but the
      mutagenicity was markedly increased by composting. The reduction in lethality
      reflected the attenuation of explosives caused by composting, as indicated by
      chemical analysis. However, the increased mutagenicity was a result that would
      not have been indicated by chemical analysis alone and is inferred to be the
      result of the formation of mutagenic metabolites of explosives during composting
      and their incomplete degradation.

PMID- 9515086
TI  - Modeling acute and chronic toxicity of nonpolar narcotic chemicals and mixtures
      to Ceriodaphnia dubia.
AB  - The response of the daphnid Ceriodaphnia dubia to six widely used industrial
      chemicals acting through nonpolar narcosis and a mixture was determined.
      Toxicological effect levels were based on reasonably steady-state, measured
      concentrations. Reproductive IC50S were 149 microM benzene, 82 microM
      trichloroethylene, 35 microM toluene, 31 microM ethylbenzene, 26 microM m-xylene,
      and 4 microM tetrachloroethylene. A QSAR describing 2-day LC50S as a function of
      log Kow accounted for 90.97% of the variation in response across chemical. A
      similar QSAR for chronic effects on reproduction accounted for 78.92%. Mixtures
      of benzene, trichloroethylene, and toluene had effects at concentrations below
      their individual LOELs. Observed effects of 20/24 mixtures tested fell within the
      95% prediction interval for a concentration-addition model of joint action
      derived from tests with individual components. However, the observed response
      differed significantly from the predictive relationship. In general, the
      predictive relationship overestimated mixture toxicity. Fitted relationships
      reduced observed error by as much as 82% compared to the predictive model.

PMID- 9515087
TI  - The effects of exposure duration and feeding status on fish bile metabolites:
      implications for biomonitoring.
AB  - Biliary metabolites of 2-chlorosyringaldehyde (2-CSA), the major chlorinated
      phenol found in chlorine dioxide bleached eucalypt pulp effluent, have been found
      to be sensitive biomarkers of effluent exposure in the sand flathead
      (Platycephalus bassensis). Before this method of biomonitoring can be applied in
      the field, the influences of exposure duration, depuration time, and fish feeding
      status on the level of this metabolite should be determined. In this study, sand
      flathead were exposed to a measured concentration of 0.3 microgram/1 of 2-CSA for
      1, 2, 4, 8, 12, or 16 days. Fish previously exposed to 2-CSA were then held in
      sea-water alone for 1, 2, 3, 4, or 6 days. Fish were fed ad libitum throughout
      the experiment, and the fullness of the fish's stomach at the time of sampling
      was noted. There were no effects of exposure on biotransformation enzyme
      activities, either between exposure times or between the exposure and depuration
      periods. The major metabolite of 2-CSA, 2-chloro-4-hydroxy-3,5
      dimethoxybenzylalcohol (2-CB-OH), was first detected in the bile of some fish
      sampled after 24 h of exposure, and the mean concentration of 2-CB-OH in the bile
      increased over the exposure period. The mean concentration (+/- SE) of 2-CB-OH in
      the bile was strongly influenced by fish feeding status, being 94 +/- 18 ng/ml
      bile in fish with empty stomachs and undetectable in fish with full stomachs.
      Bile volume was also influenced by fish feeding status, being greatest in fish
      with empty stomachs at the time of sampling. Results indicate that the feeding
      status of fish should be taken into consideration when using biliary metabolites
      as biomarkers of effluent exposure in the field, and methods to establish this
      are discussed.

PMID- 9515088
TI  - Sensitivity- and gradient-enhanced hetero (omega1) half-filtered TOCSY experiment
      for measuring long-range heteronuclear coupling constants.
AB  - An enhanced version of the X (omega1) half-filtered TOCSY experiment for
      measurement of long-range heteronuclear coupling constants is proposed which
      yields high-quality spectra with substantially increased sensitivity and
      resolution. The modified method features gradient-enhanced X filtering sequences,
      broadband homonuclear decoupling during t1, optional 1JXH scaling in the F1
      domain, and gradient coherence selection in combination with the sensitivity
      enhanced protocol for the TOCSY transfer. These modifications extend the
      applicability of the method--coupling constants can be measured accurately for
      natural abundance samples at low concentrations and for compounds yielding
      complex spectra. Computer-aided analysis of E.COSY-type multiplets is applied for
      the determination of heteronuclear long-range coupling constants.

PMID- 9515090
TI  - Differential Line Broadening in the Presence of Quadrupolar-CSA Interference
AB  - The formalism for calculating the lineshape of a spin 1/2 J-coupled to a high
      spin nucleus undergoing quadrupolar and chemical shift anisotropy (CSA)
      relaxations is derived in the case where the tensors of both interactions are
      noncoincident and nonaxial. The expressions show that the CSA-quadrupolar
      interference term which is responsible for the asymmetry of lines involves a term
      depending on tensorial parameters. The effect of this term on the lineshapes is
      discussed with respect to three cases, namely coincident-axially symmetric,
      noncoincident-axially symmetric, and general noncoincident quadrupolar and CSA
      tensors. These cases are considered in the analysis of the lineshape of the 1H
      decoupled spectra of the 31P nucleus J-coupled to the 59Co nucleus encountered in
      the tetrahedral cluster HFeCo3(CO)11PPh2H. Copyright 1998 Academic Press.

PMID- 9515089
TI  - Contributions of spin-lattice relaxation to the echo decay of planar Cu in high
      temperature superconductors.
AB  - Measurement of T2G, the Gaussian component of the spin-echo envelope of planar Cu
      nuclei in high-temperature superconductors, gives important information about the
      real part of the Cu electron spin susceptibility. In the traditional picture of
      the planar Cu echo decay, the internuclear coupling is assumed to remain static
      with respect to spin-lattice relaxation and mutual exchange fluctuations. In some
      circumstances, however, this assumption breaks down. We calculate the
      internuclear corrections arising from spin-lattice relaxation to the conventional
      theory of T2G and show that T2G can be easily corrected for these effects. We
      argue that mutual exchanges due to the perpendicular indirect couplings are
      suppressed in these materials. For YBa2Cu4O8, we find a correction on the order
      of 10% in T2g and using the corrected values we find that the isotope ration
      63T2G/65T2G agrees with theory.

PMID- 9515091
TI  - Influence of High Orientational Order on the Shape of the Echo Response from a
      Hahn Pulse Sequence
AB  - The amplitude modulations in the simulations of the Hahn echo responses from
      cholestane spin labels in samples characterized by a high degree of orientational
      order are shown to arise from the use of "soft" pulses. Soft pulses have a
      limited spectral range and cover only a small portion of the CW-ESR spectra, so
      that not all the spins are on-resonance. The magnetization vectors of the off
      resonance spins only partially tilted away from the laboratory z axis, the
      direction of the applied static magnetic field. They thus contribute oscillating
      components to the magnetization in the xy plane. The contribution from the off
      resonance spins to the Hahn echo formation is significant in highly oriented
      samples, but cancels out in samples exhibiting a small degree of order.
      Experimental echo responses obtained from CSL molecules embedded in rigid
      matrices of eggPC bilayers and the liquid crystalline materials ZLI and MBBA
      confirm the theoretical predictions. Copyright 1998 Academic Press.

PMID- 9515092
TI  - A Radiofrequency (220-MHz) Fourier Transform EPR Spectrometer
AB  - Radiofrequency continuous wave EPR spectrometers for detecting and localizing
      free radicals in vivo in samples of 50-100 g have been developed. The main
      limitation of these EPR instruments is the slow acquisition time, and a sensible
      improvement is expected by the adoption of pulsed EPR techniques. We present here
      a Fourier transform EPR spectrometer operating at 220 MHz suitable for large
      volume samples (up to 50 ml). A detailed description of the transmitter and
      receiver sections, including the EPR resonator, is given. Representative free
      induction decay data obtained from a sample with a relaxation time of about 900
      ns are reported. Copyright 1998 Academic Press.

PMID- 9515093
TI  - Improved Resolution from Double Constant-Time Evolution of 3D and 4D Triple
      Resonance Experiments
AB  - Triple-resonance NMR experiments are nearly essential for performing backbone
      assignments of proteins larger than approximately 15 kDa. Our work extends the
      double constant-time (2CT) evolution scheme to triple-resonance 3D and 4D
      experiments. The modifications needed to accomplish 2CT evolution in triple
      resonance experiments are straight forward, are completely general, and
      consequently, will yield increased resolution for all out-and-back experiments.
      We expect that the increased resolution of experiments presented here will be
      useful in the study of larger proteins (>30 kDa) and in the study of highly
      helical proteins where 1HN, 15N, and 13C dimensions are poorly dispersed.
      Copyright 1998 Academic Press.

PMID- 9515095
TI  - [General internal Medicine applied to elderly patients: lessons for the near
      future].

PMID- 9515096
TI  - [Dementia syndromes and length of stay of elderly patients in internal medicine].
AB  - Dementia is frequently observed in elderly patients admitted in Internal Medicine
      Units. Study of prospective data allowed comparison between 199 demented patients
      and 601 non demented ones, for life conditions, hospitalization parameters, way
      of discharge and associated diseases. Age and sex ratio are equal. Demented
      patients live more frequently in geriatric institutions and require more often
      nurse care at home. For them, social care is more frequent during
      hospitalization. There is no significant difference for mean duration of stay,
      discharge in step down unit and mortality. In both groups the predictive factors
      for the duration of stay are the need for social care during hospitalization and
      the number of comorbidities. In patients with degenerative dementia, hypertension
      and cardiopathies are less frequent than among other patients. These data suggest
      that adequate care, including social care, may produce the same duration of stay
      and way of discharge for demented and non demented elderly patients in Internal
      Medicine Units.

PMID- 9515097
TI  - [Scleroderma with anomalies of the thyroid function. 7 cases].
AB  - Thyroid function, studied in 36 scleroderma patients revealed 7 abnormal cases: 6
      hypothyroid patients secondary to autoimmune thyroiditis and 1 hyperthyroidism
      secondary to Graves' disease. In the hypothyroid subgroup, 3 cases presented a
      localized systemic sclerosis and the 3 others presented a diffuse systemic
      sclerosis; Sjogren syndrome was found in 2 of these patients. The hyperthyroid
      patient presented a diffuse systemic sclerosis. Because of the association
      between scleroderma and thyroid diseases, we suggest to perform thyroid screening
      regularly for all patients with systemic sclerosis.

PMID- 9515098
TI  - [Viral inactivation of fresh frozen plasma].
AB  - Despite the progress made in screening for blood-transmitted diseases, both the
      post-infection diagnostic window and the appearance of novel infective agents
      remain critical issues for the safety of blood transfusions. Viral inactivation
      methodologies for fresh-frozen-plasma (e.g., treatment with methylene blue or
      solvent-detergent) are currently being compared, in terms of their activities on
      viral subtypes and coagulation factors, as well as general toxicity and clinical
      effects, in order to define the advantages, residual risks and the uncertainties
      involved in their use.

PMID- 9515099
TI  - Pulmonary artery thrombosis in giant cell arteritis. A new case and review of
      literature.
AB  - Pulmonary artery thrombosis caused by giant cell arteritis is an extremely rare
      condition. We report the case of an 86-year-old woman, who was hospitalized for
      dyspnea. Pulmonary artery thrombosis was confirmed by pulmonary angiogram and was
      linked to giant cell arteritis. This observation is accompanied by a discussion
      of the literature.

PMID- 9515100
TI  - [Mercury erythema after accidental exposure to mercury vapor].
AB  - Mercury exanthem can be considered as a systemic contact dermatitis following
      exposure to mercury vapor in patients with a prior sensitization to mercurials.
      It is characterized by a symmetrically distributed erythematous eruption
      appearing predominantly in the major flexural areas, in the neck, the lower
      portion of the abdomen and the upper anteromedial part of the thighs. In some
      cases, small pustules develop over the erythematous surfaces. We report our
      observations of two patients with mercury exanthem after exposure to mercury
      vapor caused by a broken thermometer. One of these patients presented with an
      unusual bullous form of mercury exanthem. Although diagnosis of mercury exanthem
      can be essentially based on clinical features, confirmation of the patient's
      exposure to mercury should be obtained. Cutaneous patch tests often prove the
      sensitization to mercurials.

PMID- 9515101
TI  - Tropical pulmonary eosinophilia. Report of a case.
AB  - Tropical pulmonary eosinophilia (TPE) is an unusual manifestation of filarial
      infection, most commonly found in South-East Asia and caused by immunologic
      hyperresponsiveness to Wuchereria bancrofti and Brugia malayi. This report
      concerns a case of TPE in a 25-year-old Indian male who had been living in Italy
      for two years and was admitted to hospital with chest pain. Diethylcarbamazine
      therapy proved effective in rapidly eliminating symptoms and pulmonary
      abnormalities, as well as normalizing of laboratory findings.

PMID- 9515102
TI  - [Acute toxoplasmic hepatitis in an immunocompetent adult].

PMID- 9515104
TI  - [Peritoneal carcinosis with cutaneous metastases in an endocrine tumor of the
      pancreas].

PMID- 9515103
TI  - [Pancreatic pseudo-aneurysms in systemic lupus].

PMID- 9515105
TI  - [Prolonged fever in adults with normal sedimentation rate].

PMID- 9515106
TI  - [Neurologic toxicity of aciclovir apropos of a nw observation].

PMID- 9515107
TI  - [Idiopathic muscular granulomatosis: apropos of a case].

PMID- 9515108
TI  - [Endothelial dysfunction in cardiovascular pathology].

PMID- 9515109
TI  - [Endothelial dysfunction and atherosclerosis].
AB  - Mammalian endothelium acts as a mediator in arterial and venous relaxation and
      contraction. Endothelium-dependent relaxation is due to endothelial release of
      powerful, non-prostanoid vasodilatory substances. The best known of these is the
      endothelial factor EDRF identified as nitrous oxide (NO). It is the end result of
      the metabolism of L-arginine by the NO synthetase of endothelial cells. In
      arterial smooth muscle, the relaxation induced by EDRF is explained by NO
      stimulation of soluble guanylate cyclase, leading to accumulation of GMPc (cyclic
      guanosine monophosphate). In some animal vessels and in human coronary arteries,
      endothelial cells release a substance which induces hyperpolarisation of the cell
      membrane (endothelial derived hyperpolarising factor, EDHF). Release of EDRF by
      the cell membrane may be mediated by G proteins sensitive to pertussis toxin
      (activation of the alpha 2 adrenoreceptor, serotonin, platelet aggregation,
      leukotrienes) or non-sensitive G proteins (adenosine-diphosphate (ADP),
      bradykinin). In animal blood vessels where the endothelium is regenerated and
      reperfused, and/or atherosclerotic, a selective loss of the mechanism of EDRF
      release is observed, sensitive to pertussis toxin, which favors vasospasm,
      thrombosis and cellular proliferation. The available data on isolated or in situ
      human blood vessels concord with studies on isolated animal tissues. In addition
      to the relaxation factors, endothelial cells can also secrete contracting factors
      (endothelium derived contracting factors: EDCF); these include superoxide anions,
      endoperoxides, thromboxane A2 and endothelin. Animal studies indicate that the
      tendency to release EDCF is maintained or even increased in damaged vessels. The
      change from normally dominant EDRF release to EDCF release could play an
      important role in atherosclerosis.

PMID- 9515110
TI  - [Coronary endothelial dysfunction in hypertension].
AB  - Intracoronary injection of acetylcholine leads to coronary vasodilatation in
      normal subjects and vasoconstriction in hypertensive subjects, suggesting an
      abnormality of endothelial function in hypertension. In order to study the
      response to physiological stimulation which induces endothelium-dependent
      vasodilatation, the effects of sympathetic stimulation (cold pressor test) and of
      the increase in flow velocity in the left anterior descending artery were
      analysed in 10 control and 26 hypertensive subjects. All had angiographically
      normal coronary arteries and normal lipid profiles. None of the subjects were
      smokers or diabetic. During the cold test (12 patients), the flow velocity
      increased by 47 +/- 26% (p < 0.05) in controls and by 68 +/- 48% (p < 0.01) in
      the hypertensives. Dilatation of the coronary arteries was observed in controls
      (+12.0 +/- 4.5%, p < 0.001) and constriction in the hypertensives (-10.3 +/-
      8.5%, p < 0.001). Injection of papaverine in the distal left anterior descending
      artery (14 patients) induced proximal dilatation in controls (+17.0 +/- 10.6%, p
      < 0.001) and was ineffective in hypertensives (-0.4 +/- 1.5%), whereas the flow
      velocity increased by 521 +/- 129% and 406 +/- 120% (p < 0.001) respectively.
      Intracoronary injection of 2 mg of isosorbide dinitrate induced comparable
      dilatation in control subjects (+30.0 +/- 12.9%, p < 0.001) and in the 26
      hypertensives (+22.8 +/- 6.5%, p < 0.001). In 10 hypertensive patients,
      intravenous injection of an angiotensin converting enzyme inhibitor,
      perindoprilat, immediately re-established the vasodilatory response to these two
      stimuli. The authors conclude that the coronary responses to physiological
      stimuli (sympathetic stimulation, increase in flow velocity) are altered in
      hypertensive subjects with angiographically normal coronary arteries with no
      other risk factors. Normal vasomotion may be restored by an angiotensin
      converting enzyme inhibitor.

PMID- 9515111
TI  - [Endothelial dysfunction in cardial failure: potential mechanisms].
AB  - From the vascular point of view, cardiac failure is characterised by increased
      systemic resistances secondary to an increased concentration of a number of
      vasoconstrictor substances and also to decreased endothelium dependent
      vasodilatation. Endothelial dysfunction has been described both in man and in
      animal models, but its causes are not well understood. Such dysfunction could be
      due to a decrease in the production of nitric oxide, a decrease in its
      vasodilator effect due to an increased degradation or an increased
      vasoconstrictor tone. Recent data suggests an improvement or prevention of this
      endothelial dysfunction observed in cardiac failure by physical training and by
      chronic treatment with an angiotensin converting enzyme inhibitor. The
      improvement or preservation of endothelial function induced by exercise or ACE
      inhibitor could explain some of the benefits of these treatments in terms of
      tissue perfusion and haemodynamic conditions.

PMID- 9515112
TI  - [Endothelial dysfunction in cardiovascular diseases: therapeutic implications
      after coronary angioplasty].
AB  - Restenosis remains the principal limitation of coronary angioplasty; its main
      mechanisms are neointimal hyperplasia and vascular remodeling. The endothelium
      destroyed at angioplasty will progressively recover the denuded zone. However,
      dysfunction of this neo-endothelium persists for quite a period and may
      participate in restenosis by influencing these two components (hyperplasia and
      remodeling). Several therapeutic strategies are under evaluation to try and
      accelerate the regeneration of the endothelium and make it functional more
      rapidly. Increasing available nitric oxide (NO) decreases the hyperplasia and
      improves endothelial function. Growth factors accelerate the endothelial
      regeneration and improves its function: the effect on hyperplasia depends on the
      growth factor used. The angiotensin converting enzyme inhibitors decrease
      hyperplasia by improving endothelial function. These therapeutic strategies merit
      evaluation in the clinical setting.

PMID- 9515113
TI  - Present concepts of coronary atherosclerosis-thrombosis, therapeutic implications
      and perspectives.
AB  - Our knowledge of the pathophysiology of coronary atherosclerosis has remarkably
      changed in the last few years. The types of atherosclerotic lesions, the
      mechanisms of progression of coronary atherosclerosis with plaque instability and
      disruption, and the subsequent thrombotic phenomenon leading to acute coronary
      syndromes are now better understood. Therapeutic strategies leading to
      atherosclerotic lesion stabilization and even regression, as well as new
      antithrombotic strategies to alleviate or prevent the thrombotic complications
      are being pursued. This review focuses on the coronary unstable atherosclerotic
      plaque and complicating thrombosis.

PMID- 9515114
TI  - [Acyclovir overdose in patients with renal failure: neuro and nephrotoxicity].

PMID- 9515115
TI  - [Correction of low-grade and mild myopia using Schwind Excimer laser].
AB  - PURPOSE: To examine the results of Excimer laser photorefractive keratectomy on
      myopic eyes. To demonstrate the efficacy, safety, predictability and stability of
      the Schwind Keratom laser. METHODS: Two hundred and fifty three patients were
      operated, with myopia from -0.75 to -8 D and cylinder of less than 1.50 D.
      Ablation zone diameters were from 5.3 mm to 6.5 m. The follow-up was one year.
      RESULTS: One year after the operation, 92% of myopic eyes have uncorrected visual
      acuity above 20/40, 90% have best corrected visual acuity at least equal to that
      evaluated before treatment, 94% were within (1 D without correction. Between 6
      months and one year, the spherical equivalent varied in only 4% the patients.
      CONCLUSIONS: The results with the Schwind Keratom laser are excellent and at
      least comparable with the other lasers. The best results are obtained with low
      myopia. At the end of this study, the Schwind Keratom laser was certified in
      France.

PMID- 9515116
TI  - [Management of congenital microphthalmos and anophthalmos].
AB  - PURPOSE: To better characterize congenital anophthalmos and microphthalmos in
      order to distinguish which patients need surgical treatment. MATERIALS AND
      METHODS: A retrospective study of 42 cases with congenital anophthalmos and
      microphthalmos over a 16 years period was performed. Seven anophthalmos, 20
      microphthalmic globes with no associated colobomatous orbital cyst and 15
      microphthalmic globes associated with colobomatous orbital cyst were observed.
      Complete history, pediatrical and ophthalmological examination,
      electrophysiological feature, oculo-cerebral imagery and karyotype on each of the
      patients were reviewed. RESULTS: Among all patients, lack of development of the
      lids was observed in 45% of cases. In our group of anophthalmos, 100% had micro
      orbit. In our group of microphthalmic globes with no associated colobomatous
      orbital cyst, 30% had micro-orbit and in our group of microphthalmic globes
      associated with colobomatous orbital cyst, 6% had micro-orbit. 75% of patients
      had ocular anomalies and 39% had systemic anomalies, mostly on the face.
      Aetiology were found in 36% of cases. Visual evoked potentials and retinal
      electric feature were useful to better determine visual function. CONCLUSION:
      Expandable orbital prosthesis would appear to be the most effective therapy for
      certain cases of anophthalmos and microphthalmos with micro-orbit.

PMID- 9515117
TI  - [Ophthalmological involvement in Behcet disease. Apropos of 520 cases].
AB  - PURPOSE: The aim of this paper is to compare our results with the literature and
      to discuss some therapeutical aspects of the disease. METHODS: This retrospective
      study concerned 520 cases of Behcet's disease followed by internal diseases
      department and ophthalmology service of U.H.C. Averroes (Casablanca, Morocco)
      during 10 years. RESULTS: There were 432 men (83%) and 88 women (17%). The mean
      age of the patients was 20 years. Ophthalmological involvements are found in 80%,
      bilateral in 60%. The disease occurred at the rate of 2 or 3 episodes a year in
      5% of cases. Irreversible blindness was noted in 24.4% of cases, predominately
      panuveitis in 37% of cases, followed by anterior uveitis in 36.3% and retinal
      vasculitis in 37% of cases. Good results were obtained by a medical care with
      corticoids and chloraminophen in case of threatening blindness. CONCLUSION:
      Behcet's disease remains frequent in our country. It requires early diagnosis and
      steady ophthalmological surveillance in order to delay onset of blindness.

PMID- 9515118
TI  - [Electro-functional changes in pseudo-exfoliative syndrome].
AB  - PURPOSE: Up to date the pathogenetic aspects of exfoliation syndrome which are
      not well agreed upon even though the vascular damage plays a major role. METHODS:
      In order to evaluate the electrophysiological changes occurring in patients
      affected by exfoliation syndrome a case-control study with pattern
      electrofunctional examinations and oscillatory potentials from standard flash-ERG
      in 80 eyes affected by exfoliation syndrome with or without ocular hypertension
      was undertaken. RESULTS: Some statistically significant PERG, P-PEV and OP
      abnormalities were found in eyes affected by exfoliation syndrome with or without
      ocular hypertension (p < 0.001). There is no statistically significant difference
      between affected and control eyes in monolateral syndrome (p > 0.05). The
      electrofunctional examination did not mark any statistically significant
      difference between eyes with and without ocular hypertension (p > 0.05).
      CONCLUSION: The results stressed by pattern and oscillatory potentials
      examinations may support the hypothesis of a primitive change of the optic nerve.

PMID- 9515119
TI  - [Orbital schwannoma. Apropos of a case].
AB  - The orbital schwannoma or neurilemoma is a rare tumor. We report herein the
      single case of a 51-year-old woman presenting an inferior extraconal orbital
      schwannoma and multiple sclerosis. Surgical treatment with complete excision
      allowed healing.

PMID- 9515120
TI  - [Uncommon corneal hydrops. Apropos of a case].
AB  - We report a case of corneal hydrops in a young patient with unremarkable
      ophthalmologic history or intercurrent identified pathology. Different etiologies
      of corneal hydrops are discussed.

PMID- 9515121
TI  - [Confocal microscopy study of 2 cases of Thygeson's epithelial keratitis].
AB  - Two cases of bilateral Thygeson's keratitis were examined by in vivo confocal
      microscopy. In the corneas, fine deposits of highly reflected material appeared
      immediately below the basal lamina. This is the first time that such
      morphological features are described in patients with Thygeson's keratitis.

PMID- 9515122
TI  - [Subconjunctival adipose hernias of the orbit].
AB  - Clinical report of three cases of subconjunctival fat prolapse. Differential
      diagnoses are discussed. Subconjunctival orbital fat prolapse is a benign entity
      with a fat herniation through defective Tenon's capsule.

PMID- 9515123
TI  - [Mooren's ulcer following combined extracapsular crystalline lens extraction and
      trabeculectomy].
AB  - We report the case of a 70-year-old patient who presented with Mooren's ulcer in
      her right eye following extracapsular cataract extraction combined with
      trabeculectomy. She was successfully treated by a sclerocorneal graft combined
      with a large conjunctival resection. Clinical and histological features, and
      therapeutic outcomes are discussed and compared to previously published data.

PMID- 9515124
TI  - [Retinopathy caused by interferon. Apropos of a case].
AB  - Toxic retinopathy due to alpha interferon in a 20-year-old female is reported.
      This was an unusual case due to its severity in a non diabetic patient. Recovery
      of visual acuity was incomplete though angiographic tests normalized. Retinal
      toxicity in nondiabetic patients is usually reversible, suggesting careful
      surveillance of high risk patients with retinal microangiopathy given interferon
      therapy.

PMID- 9515125
TI  - [Factors of endothelial cell loss during phacoemulsification. Update].

PMID- 9515126
TI  - [Macular epiretinal membrane and cataract].

PMID- 9515127
TI  - [Effect of external extra-articular ligament plasty on the results of anterior
      cruciate ligament reconstruction with patellar tendon, a 4 years follow-up].
AB  - PURPOSE OF THE STUDY: The purpose of this study was to compare the functional
      results obtained when an external extra-articular plasty was added to an anterior
      cruciate ligament (ACL) reconstruction using an autologous bone tendon-bone
      patellar tendon graft. MATERIAL AND METHODS: The authors analyzed two consecutive
      series of 60 and 50 patients operated by the same surgeon for a chronic rupture
      of the anterior cruciate ligament, one by reconstruction of the cruciate ligament
      with a free graft of the patellar tendon supplemented by an external extra
      articular plasty made with a quadriceps tendon graft and the second with an
      isolated free patellar tendon graft. Anterior laxity was measured before and
      after surgery, by dynamic X-rays and by the Medmetric KT-1000 arthrometer.
      Functional results were evaluated four years after operation, with the French
      A.R.P.E.GE score based on sport activity level and intensity. RESULTS: Anterior
      laxity was not different before operation in both groups and there was no
      difference between males and females. Medmetric KT-1000 arthrometer showed the
      same negative differential laxity immediately after surgery in both groups and
      the same evolution during the first 4 years, without any significant difference
      on laxity on the middle aspect of the knee. Radiological results were different.
      After a 4 years follow-up, anterior laxity did not show significant difference on
      the medial compartment of the knee (5.3 +/- 2.3 mm and 5.5 +/- 1.7 mm), but there
      was a significant minor laxity in the lateral compartment for the lateral extra
      articular plasty group (11.0 +/- 2.3 mm against 14.8 +/- 3.8 mm)(p = 0.002).
      Functional results and sport activity were similar in both groups. Examination
      showed 4 positive pivot shift tests (2 "sliding" and 2 positive) in the group
      with extra-articular plasty, even though 8 positive pivot shift tests in the
      isolated ACL group (5 "sliding" and 3 positive) were found. DISCUSSION: This
      study, as well as five others studies found in literature, was not randomized. In
      all these series, the surgical techniques, the rehabilitation programs and the
      functional score evaluation were too different to allow any pertinent comparison.
      Extra-articular plasty helps to control the laxity of the lateral compartment of
      the knee which is incompletely controlled by ACL reconstruction, particularly in
      chronic cases. This is proved by radiological measurements and pivot shift tests.
      Jensen in 1983, about 205 patients with a 4 year follow-up and Noyes, which used
      an allograft patellar tendon, found an advantage to do extra-articular plasty.
      But Strum (in 1989), as O'Brien (in 1991) and Roth (in 1987), did not found any
      advantage with extra-articular plasty. CONCLUSION: It is therefore obvious, after
      a four-year follow-up, that extra-articular supplementation presents an advantage
      for reconstruction of the ACL. by a free graft of the patellar tendon in chronic
      cases. Further randomized study will confirm that isolated ACL reconstruction is
      possible in some well defined categories of anterior laxity.

PMID- 9515128
TI  - [Value of external fixation in proximal tibial fractures].
AB  - PURPOSE OF THE STUDY: This study was a retrospective analysis of 39 proximal
      metaphyseal tibial fractures treated by Orthofix fixator in two trauma
      departments. MATERIAL AND METHOD: There were 28 men and 10 women with a mean age
      of 49.5 years. 13 pedestrians were stroked by a car and 18 had a traffic accident
      on a motorcycle. In 27 cases, the fracture was open with following Cauchoix
      grading: 15 types 2, 6 types 1 and 6 types 3. All fractures were partially or
      totally included in the proximal epiphyseal square of the AO system. 14 fractures
      were metaphyseal, 13 diaphyso-metaphyseal and 12 had an articular irradiation.
      All external fixations were performed using the Orthofix device, with image
      intensification. A partial weight bearing was allowed for 2.4 months as an
      average and full weight bearing at mean 3.7 months. 7 skin grafts, 2 micro
      surgical (latissimus dorsi) and 2 local flaps were necessary. RESULTS: In 3
      patients this technique failed. 3 patients had an autologous bone graft at the
      metaphyseal and 2 at the diaphyseal fracture site. 30 patients healed without
      other procedure after an average delay of 5.5 months. During the healing and
      weight bearing time, 6 frontal deformities appeared and 5 flexion contractures
      were not reoperated. With a minimum follow up of one year (mean 3 years) 22
      fractures had no deformity, 8 had a valgus deformity (5 degrees to 10 degrees)
      and 3 a varus deformity (6 to 17 degrees). For the 25 patients with an isolated
      proximal tibial fracture, 11 (44%) had an excellent functional result (no pain,
      full range knee motion, normal daily activity); 12 (48%) had a good result
      (episodic pain, minimally knee discomfort, flexion limitation). DISCUSSION:
      Orthofix fixator appear to be a good solution for comminuted fractures. These
      fractures have anatomical and epidemiological particularities. AO classification
      system is not useful; a new one is proposed. External fixator must be placed
      meticulously after closed fracture reduction.

PMID- 9515129
TI  - [Effect of osseous torsions of the lower limb on the development of lateral
      femorotibial knee arthrosis].
AB  - PURPOSE OF THE STUDY: Frontal deformation of the knee is certainly not the only
      factor involved in the occurrence of lateralised tibio-femoral arthrosis. The aim
      of the study was to analyze if any kind of tibial torsion or femoral torsion
      could be able to induce lateralized arthrosis. MATERIAL AND METHODS: Femoral
      torsion, tibial torsion and tibio-femoral index (tibial torsion minus femoral
      torsion) have been measured on 59 knees with lateral arthrosis (8 knees) or with
      medial arthrosis (51 knees). For each knee, two frontal deformations were
      measured: 1) the actual arthrosis deformation was calculated on a hip knee ankle
      radiograph, 2) the pre arthrosis deformation is the arthrosis deformation minus
      the angle made by the femoral condyle tangent and the tibial plateau tangent. A
      knee has no frontal deformation if the angle between the mechanical axis of the
      femur and the mechanical axis of the tibia is between 178 degrees and 182
      degrees; there is a varus deformity if the angle is inferior to 178 degrees;
      there is a valgus deformation if the angle is superior to 182 degrees. RESULTS:
      Out of the 8 knees with lateral arthrosis, 2 showed initially no frontal
      deformation and 6 had a valgus deformation; out of the 51 knees with medial
      arthrosis, 34 showed initially no frontal deformation, 6 had a valgus deformity
      and 11 a varus deformity. The tibio-femoral index in lateral FT arthrosis was
      statistically different from those in medial FT arthrosis (p 0.0001). When a
      lateral arthrosis appeared whatever the pre arthrosis deformation was the index
      was always negative (tibial torsion lower than femoral torsion); when a medial FT
      arthrosis appeared, whatever the pre arthrosis deformation was, the index (except
      for two cases) was always positive (tibial torsion higher than femoral torsion).
      CONCLUSION: Femoral and tibial torsions play a part in lateralised arthrosis
      occurrence together with frontal mechanical factors. Perhaps troubles in torsion
      explain some spontaneous or post-therapeutic evolutions not explained by frontal
      mechanical factors.

PMID- 9515130
TI  - [Severe motor weakness associated with lumbar spinal stenosis. A retrospective
      study of a series of 61 patients].
AB  - PURPOSE OF THE STUDY: Severe motor weakness is a rather infrequent symptom in the
      course of lumbar stenosis. The objectives of this study are three fold: describe
      the motor deficit, evaluate the prognosis factors and determine the type of
      stenosis the most likely to be complicated by motor loss. MATERIAL AND METHODS:
      61 consecutive patients with a mean age of 63 years, operated on for a lumbar
      stenosis and with a severe motor deficit have been retrospectively studied. The
      mean follow-up was 38 months. The overall functional result was evaluated
      according to a rating scale, specially developed in our unit for the follow-up of
      lumbar stenosis. The motor capacity was rated from 0 (complete paralysis) to 5
      (normal strength). According to that scale the motor weakness was rated as 0, 11
      times as 1, 11 times, as 2, 11 times and as 3, 28 times. The deficit was
      unilateral in 79 per cent of cases and multiradicular in 58 per cent of patients.
      Sphincter abnormalities were also present in 9 cases. In 9 out of 10 patients the
      motor deficit was in the L5 territory. Stenosis was extended to 3 levels in 30
      cases and was focal in the remaining cases. Degenerative spondylolishthesis was
      disclosed in 20 patients. In 3 out of 4 cases decompression was performed after 3
      weeks of motor weakness and within 3 weeks in the remaining cases. RESULTS:
      According to our rating scale the overall results were considered excellent in 29
      cases, good in 21 cases and fair in the 11 remaining cases. There was no
      complication, and no postoperative worsening of the deficit was observed.
      Regression of motor weakness was complete 22 times, partial 29 times and null 10
      times. In the eleven complete deficits with a 0 cotation one receded completely,
      7 receded partially and no improvement was noted in the 3 remaining cases. 6 out
      of the 9 patients with sphincter abnormalities recovered completely. In this
      study favourable prognosis parameters were as follows: age under 62 years,
      monoradicular deficit, stenosis at one level and association with a discal
      herniation. In contrast, severity of the initial motor weakness, association with
      sphincter abnormalities, presence or not of degenerative spondylolisthesis, or of
      a complete block on the myelogram were not influential variables. Chances of
      recovery were statistically diminished when decompression was performed after 6
      weeks. DISCUSSION AND CONCLUSION: No study dealing specifically with the
      postoperative outcome of motor deficit caused by lumbar stenosis has been
      published. However the rate of motor recovery (complete or partial) disclosed in
      our series is comparable with that found in other series dealing more generally
      with the overall post-surgery outcome. At our last follow-up, 82 per cent of our
      patients were considered as having an excellent or good result. It can be
      concluded that the existence of a motor deficit is not a major pejorative factor
      of the overall final functional result. Motor weakness is more frequently
      observed in elderly patients, in cases with degenerative spondylolisthesis, or
      when a discal herniation is associated with a bony compression. Chances of
      recovery are better, when the deficit is monoradicular, when the stenosis is
      focal, or associated with a discal herniation and when the patient is relatively
      young.

PMID- 9515131
TI  - [Evaluation of the direct cost of trochanteric fractures in the elderly].
AB  - PURPOSE OF THE STUDY: The cost effectiveness of trochanteric hip fractures in
      1995 at Pitie-Salpetriere Hospital in Paris has been thoroughly analysed. The aim
      of this retrospective study was to identify the factors responsible for the
      variation in the treatment cost of those fractures. MATERIAL AND METHODS: Cost,
      Hospital stay, functional status, ASA score, mental status and surgical treatment
      were analysed in 74 patients aged over 60 years old. RESULTS: The mean cost per
      patient was 23,901 FF divided as follows: 8.5 per cent for preoperative care,
      40.5 per cent for surgical procedures, 51 per cent for post-operative care. The
      mean hospital stay was 18 days. The cost of hospital personnel (44 per cent) and
      medical materiel (26 per cent) were the two main sources of hospital expenses
      beside medical investigations (11 per cent), hostelry (8 per cent), blood
      transfusion (6 per cent) and drugs (5 per cent). DISCUSSION: The duration of
      hospital stay was the only factor that affected statistically the mean cost per
      patient. Furthermore, factors related to the patient as age, sex, place of
      residence prior to admission, functional status, ASA score, mental status, had no
      influence on cost variation. CONCLUSION: Therefore, the best way to reduce the
      cost of trochanteric fractures treatment is to develop convalescence structures
      to avoid a lengthy and costly hospital stay and to minimize the abuse utilization
      of medical materials.

PMID- 9515132
TI  - [Proximal femoral fractures in patients over 75 years. Vital and functional
      prognosis of a cohort of 78 patients followed during 2.5 years].
AB  - PURPOSE OF THE STUDY: The purpose of this study was to highlight factors
      influencing vital and functional prognosis at 2.5 years of elderly people being
      treated for a proximal femoral fracture. MATERIAL: The study was based on 78
      patients more than 75 years old admitted to the orthopedic department for
      emergency treatment. After post-operative care, patients were transferred to a
      geriatric readaptation unit. The average patient age at the time of surgery was
      85 years. METHODS: This was a retrospective study. Survival graphs were
      established for the entire population as well as for the sub-populations
      characterized by a studied parameter. Mortality factors were compared via a
      univariable analysis. A multivariable logistical regression analysis isolated the
      factors explaining mortality at 12, 18, and 30 months and survival at 30 months,
      as well as factors explaining functional prognosis at 1 year. RESULTS: The
      overall mortality rate was 41 per cent, 48.5 per cent of deaths occur within the
      first year. Factors which are harmful for vital prognosis are the following: high
      degree of dependence before the fracture, the existence of a neuropsychiatric
      pathology, and age factor (more than 85 years). 61.5 per cent of surviving
      patients were independent for daily activities. 77 per cent of surviving patients
      lived in their usual place of residence. Factors which were harmful for
      functional prognosis were the following: type of the fall, symptomatic of an
      underlying pathological state, and existence of a neuropsychiatric pathology.
      Nutrition was also a predictive factor concerning the patient's out come.
      DISCUSSION: The average age of the studied population was higher than in most
      studies in literature. The treatment is mainly based on hip arthroplasty. The
      group of patients of over 85 have the highest mortality rate. However, a better
      survival rate at 18 months has been observed for patients older than 90 years.
      The delay before surgical care was significantly negative if longer than 6 days.
      However, a delay of 3 to 6 days was not significantly harmful for survival.
      Within the studied population, the maximum autonomy gain was observed during the
      first 6 months. The type of non-accidental fall, symptomatic of an associated
      pathology, was a factor for functional prognosis which has not been often
      mentioned. So was the biological deficit of nutrition. Social status acted as an
      indicator of functional status evolution. CONCLUSION: Therapeutic choices can
      only be guided by assessments of patients' vital and functional prognosis. A
      sophisticated or even expensive device should be demanded for patients with
      favorable prognosis. For patients with precarious functional and vital prognosis,
      priority should be given to less invasive techniques with immediate walking. The
      cost of the device should be correlated with patient's functional investment.

PMID- 9515133
TI  - [Complications and failures of total ankle prosthesis. Apropos of 21 cases].
AB  - PURPOSE OF THE STUDY: The authors relate a heterogeneous series of twenty one
      total ankle prosthesis performed by the same surgeon with an average follow up of
      37 months. MATERIAL AND METHODS: Four types of prosthesis were implanted: 4
      Ramses, 8 New Jersey, 5 Star, 4 Freeman. The etiology was seven times a
      rheumatoid polyarthritis, ten times post-traumatic, two idiopathic arthrosis, an
      hemochromatosis and a late clubfoot sequelae. RESULTS: Results were appreciated
      according to Bousquet's criteria: 4 excellent results, 5 good, 3 fair, 9 bad. The
      ankle mobility was not improved by arthroplasty. We noticed 7 loosening whose 2
      septic occurring between 18 and 38 months after implantation of prosthesis.
      DISCUSSION: This series indicates that prosthesis should be only suggested for
      patients over sixty years old. No difference was found between post-traumatic and
      rhumatoid. The pre-operative subtalar arthrosis promoted in significant way an
      unexpected failure occurrence. CONCLUSION: Indications for total ankle
      arthroplasty must remain selected. Arthrodesis remains in the immediate future,
      the best solution for young patients with post-traumatic arthrosis.

PMID- 9515134
TI  - [Is surgical treatment of deltoid ligament rupture necessary in ankle
      fractures?].
AB  - PURPOSE OF THE STUDY: Fractures of the lateral malleolus associated with rupture
      of the deltoid ligament are severe fractures types. There is still discussion
      about wether the ruptured deltoid ligament should be sutured or not. To elucidate
      further the need for surgical repair of this structure a comparative and
      retrospective review was conducted at a mean follow-up of 4 years and 8 months.
      MATERIAL AND METHODS: Twenty nine men and 15 women were included with a mean age
      of 34 years. Patients were subdivided into two groups according to the attitude
      regarding the ligament. In the first group (n = 18), an operative repair of the
      ligament was made and in the second group (n = 17) we leaved it unrepaired. Nine
      patients were evaluated separately because of an associated osteochondral
      fracture (n = 7) or a worse reduction of the fibula (n = 2). Subjective and
      objective clinical assessment were evaluated according to a modified Cedell
      classification. Roentgenograms including A.P, lateral, mortise view and a
      external rotation stress view described by Kleiger were obtained in all patients.
      RESULTS: Subjective and objective analysis showed no significant difference
      between the two groups, likewise no differences were observed for post operative
      complications rate. Medial instability was observed in four cases (2 in group 1
      and 2 in group II). Roentgenographicaly, more ossifications of the deltoid
      ligament were founded in group II (p = 0.013), and only one degenerative
      osteoarthritis of the ankle was seen in group II. Clinical results in the group
      of patients with osteochondral fracture were statistically worse than in the two
      previous groups (p = 0.001), with frequent progression to osteoarthritis in four
      cases. DISCUSSION: In our experience it is impossible to advise surgical repair
      of the deltoid ligament in accordance to the type of lateral malleolar fracture
      like other authors have suggested. The existence of a significant widening of the
      medial space greater than 3 mm was nearly correlated with a deltoid ligament
      disruption, of the 23 patients treated with a medial approach, the ligament was
      ruptured in 22 cases. In this study, we may conclude than an untreated rupture of
      the deltoid ligament does not lead to instability. The advantages of the deltoid
      repair may be obtained if the fixation of the lateral malleolus allows a perfect
      congruency of the mortise. The most predictive radiographic factors for a poor
      outcome were a persistent widening of the medial joint greater than 3 mm, an
      associated osteochondral fracture and a poor reduction of the lateral malleolus
      which results in degenerative arthritis of the ankle at long term follow-up.
      CONCLUSION: Repair of the deltoid ligament is unnecessary if the internal
      fixation of the fibula achieves an anatomical reconstitution of the mortise.
      Exploration of the medial side is indicated only with a medial incongruency
      greater than 3 mm on intra operative roentgenograms.

PMID- 9515136
TI  - [Prevention of hemorrhagic complications in the lateral retinacular section of
      the patella. A study of the lateral arteries of the knee applied to the
      prevention of knee hemarthrosis].
AB  - PURPOSE OF THE STUDY: Arthroscopic lateral retinacular release is one of the most
      employed procedures for patellar chondromalacia. A literature review show a
      complication rate of 10 to 18 p. 100 of postoperative hemarthrosis. This work
      aims to study the vessels anatomy of the lateral side of the knee in order to
      find anatomical landmarks allowing to avoid or coagulate them. MATERIAL AND
      METHODS: Thirty-three cadaver knees were dissected. Measures were made related to
      the lateral superior genicular artery and the lateral inferior genicular artery.
      A study using tracing-paper was also carried out. The main part of the work was
      more descriptive, studying anastomosis between the different arteries and veins
      location. RESULTS: Concerning the lateral superior genicular artery, measure
      analysis showed that this artery was always cut in lateral patellar retinaculum.
      This artery never runs more than one centimeter proximally to the base of
      patella, which is too insufficient to escape from lateral retinacular release. We
      noted the possibility of locating 90 p. 100 of lateral superior genicular
      arteries in a minimal distance of 15 mm, in front of the lateral proximal angle
      of the patella. Concerning the lateral inferior genicular artery, only a few
      arteries, protected in the meniscal wall in its early course, can remain intact.
      Two thirds of these arteries are very vulnerable running across the lateral side
      of the knee. The study of the tracing-papers confirmed topographic study
      measurements. The descriptive study emphasized the number and the importance of
      anastomoses between these different arteries. Each artery is flanked by two large
      satellite veins, which also attribute a veinous origin to a possible bleeding.
      DISCUSSION: The topographic study of the lateral inferior genicular vessels shows
      that their course varies. It seems necessary to avoid their division by
      performing the standard anterior lateral inferior arthroscopic portal proximally
      to these vessels. This can be realized at the beginning of the procedure through
      cutaneous transillumination. The lateral superior genicular vessels are always
      cut. They are nevertheless reachable through a small lateral incision of about 10
      mm, distally to the lateral superior angle of the patella. 90 p. 100 at least of
      these arteries could be coagulated in such a way. We also emphasize the use of
      classical methods for the prevention of excessive venous bleeding, such as a
      compression dressing. CONCLUSION: Following this anatomical study, we suggest, as
      a supplementary precaution, a selective hemostasis of the lateral superior
      genicular vessels through a small incision associated with the location of the
      lateral inferior genicular vessels by cutaneous transillumination.

PMID- 9515135
TI  - [Too long antero-medial process of the calcaneus. A study of 59 cases in 37
      children and adolescents].
AB  - PURPOSE OF THE STUDY: In 1983, we reported 5 cases of a type of tarsal
      abnormality which often went unrecognized in children and adolescents, the so
      called "too long antero-medial process of the calcaneus" (TLAP). This report
      analyzes 59 such abnormalities observed in 37 children and adolescents. Treatment
      of the 48 symptomatic cases is presented. MATERIAL: A retrospective study was
      done on the files of all patients in whom oblique foot radiographs, CT scan or
      MRI of the foot showed an abnormal antero-medial process of the calcaneus. Of
      this group, patients were re-examined and radiographs of both feet (AP, lateral
      and oblique views) were obtained. METHODS: Gender, age at occurrence of symptoms,
      diagnosis and follow-up, patient complaints and successive treatment were
      assessed. Final clinical results were graded according to patient's complaints of
      pain and functional limitation as well as clinical evaluation of subtalar motion.
      RESULTS: Fifty-nine TLAPs have been found in 37 patients, 30 girls and 7 boys of
      11.6 years on average at the first symptoms. Delay of diagnosis from onset of
      symptoms to final diagnosis averaged 2 years. First symptoms were so-called ankle
      sprains in 19 patients, ankle instability with tarsal pain in 17, pain and tarsal
      stiffness in 11, spastic flat foot in 1. In 11 patients, the abnormality was
      found on the opposite foot. In 2 patients, the TLAP was combined to a calcaneo
      navicular bridge of the other foot. Eleven strapping managements resulted in 11
      failures, 36 plaster immobilizations led to 12 good, 2 fair and 22 poor results;
      25 resections gave 23 good, 1 fair and 1 poor result at a 4.6 years follow-up on
      average. DISCUSSION: In some people, the antero-medial process of the calcaneus
      is elongated and becomes interposed between the head of the talus and the cuboid,
      far enough to cause impingement on the navicular. Because of the elongation,
      supination produces a "nutcracker" phenomenon with compression of the process
      between the talus and the cuboid; this may result in a chondral injury of the
      talus head at its inferior and lateral part which faced the TLAP. Authors suggest
      that calcaneo-navicular coalition and TLAP represent a spectrum of types of
      errors in embryologie mesenchymal formation with lack of normal joint formation
      of the tarsal ossicles during fetal life. Immobilization treatment as primary
      management was particularly unsuccessful in the group with recurrent ankle
      sprains and persistent pain. Process resection proved a highly successful
      technique in management of those patients who failed to achieve good results with
      plaster immobilization. CONCLUSION: The "too long antero-medial process of the
      calcaneus" should be considered when assessing possible causes of recurrent ankle
      sprain or persistent tarsal pain in adolescents. An oblique X-ray is usually
      satisfactory for diagnosis. In patients who failed a conservative management,
      resection of the process produced good results and painless, supple feet.

PMID- 9515137
TI  - [Pubic tuberculous osteo-arthritis. Apropos of 2 cases].
AB  - OBJECTIVE: The authors report an exceptional site of tuberculous osteo-articular
      infection which must be diagnosed before the destructive stage. OBSERVATIONS:
      Case 1 : a 21 years old woman presented an inflammatory pubic pain after a trauma
      with weight loss of 4 kgs in 3 weeks. She presented also 2 satellite inguinal
      nodes. Erythrocyte sedimentation rate (ESR) was elevated, X-rays showed an
      important osteolysis of the left ischio-pubic rami, tuberculous skin test (TST)
      was positive, mycobacterium tuberculosis (MT) could not be found neither in
      sputtum nor in urine but the node biopsy showed the specific features of
      tuberculosis. Evolution under a 6 months antibiotic treatment was good. Case 2 :
      a 19 years old woman, with history of tuberculous contagion, presented in April
      1996 cervical nodes and a month later inflammatory pubic and knee pain with
      weight loss and vesperal sudation. ESR was elevated, TST was phlyctenular, MT
      searching and HIV serology were negative. X rays showed irregular osteolysis of
      the pubic symphysis. Scintigraphy showed an increased fixation of pubis and left
      knee. Cervical nodes biopsy diagnosed tuberculosis. Evolution was good under a 6
      months antibiotic treatment. DISCUSSION: Many factors can favorize the
      development of a pubic tuberculosis and are similar for all forms of tuberculous
      osteo-articular infection (trauma and contagion in our cases). Radiological
      features, characterized by a slow evolution, are note specific. Diagnostic
      confirmation must be bacteriologic or pathologic, and if possible far from the
      pubic foci. Any traumatic medical procedure has to be avoided because of painful
      outcome and local risk. Evolution under specific treatment, even of short course
      (6 months), is sufficient for a good outcome. CONCLUSION: One must think to pubic
      tuberculous osteo-arthritis in any pubic pain even if it is post-traumatic
      especially, in endemic countries of tuberculosis.

PMID- 9515138
TI  - [Use of "foot-bank" tissue to cover amputation stumps. Apropos of 4 cases].
AB  - PURPOSE OF THE STUDY: The authors report 4 cases of plantar skin free transfer to
      cover an amputation stump. MATERIAL AND METHODS: In two cases, operated as
      emergencies, a flap based on the posterior tibial pedicle was harvested from a
      non-reimplantable extremity. In one case the calcaneum was included in the flap
      to provide a stump wide enough to hold a prosthesis. The two others cases
      concerned planned amputation of non-functional extremities, with free transfer of
      the available plantar skin areas. RESULTS: All 4 patients healed well and the
      skin coverage provided a good quality stump which was rapidly equipped with
      prostheses. DISCUSSION: Covering amputation stumps with a free flap from the foot
      bank has proven to be a reliable procedure, economic for the patient, affording a
      good physiologic bearing surface. CONCLUSION: This method should proposed in
      emergency amputations according to local conditions, and may also be advantageous
      in some cases of secondary surgery.

PMID- 9515139
TI  - [Apropos of "A morphometric study of femoropatellar joint from lateral x-rays
      view"].

PMID- 9515140
TI  - [Role of D-dimers in the diagnosis of thromboembolic disease].
AB  - The presence of D-dimers in the bloodstream is secondary to fibrin formation and
      lysis. Because fibrin is the main component of a thrombus, deep vein thrombosis
      and/or pulmonary embolism may be excluded with a predictive value of more than
      95%, provided D-dimer plasma concentration is below a critical, assay-dependent
      cutoff. The D-dimer test is thus an ideal screening step in outpatients
      clinically suspected of venous thromboembolism. Only ELISA tests have been
      validated in clinical practice at present time for this indication, sensitivity
      of latex assays being insufficient.

PMID- 9515141
TI  - [Diagnostic approach of pulmonary embolism by spiral angioscanner].
AB  - Spiral volumetric computerized tomography (CT) allows the exploration of the
      whole chest during a single contrast injection and breath-hold. For the diagnosis
      of central pulmonary embolisms, the sensibility is between 78 and 98% and the
      specificity between 86 and 94% depending on the direct visualization of the
      endoluminal defect. Detection of intercurrent parenchymal pathologies or of non
      obstructive arterial thrombi explain some false positive or inconclusive results
      of the ventilation-perfusion scintigraphy. Sub-segmental thrombi are less easily
      detected and sensibility for both central and sub-segmental embolisms is only
      63%, explaining some rare false negatives of the CT on isolated sub-segmental
      embolisms. Chronic thrombi are outlying and contiguous with the arterial wall.
      They are associated with arterial stenosis, cut-off and loops and an oligemic
      mosaic pattern of the parenchyma. CT allows pre-operative staging before surgical
      recanalization and the intra-venous injection does not interfere with the
      arterial pressure. CT is a non-invasive, reliable and easily available technique
      which clearly plays an important role in the diagnosis of pulmonary embolism.

PMID- 9515142
TI  - [Estrogen therapy and venous thromboembolic disease].
AB  - A link between venous thromboembolism and oral contraceptive users is well
      established. This paper analyzes recent epidemiological studies affecting risk of
      venous thromboembolism with the use of oral contraceptive or with postmenopausal
      hormone replacement therapy. Four epidemiological studies showed a two-fold
      increase of venous thromboembolism with the use of oral contraceptives containing
      third generation progestins (gestodene and desogesterel, relative to second
      generations product (levonorgestrel); relative risk 3.8 per 100,000 women years
      in non-user women, 16 per 100,000 women years in women using levonorgestrel
      containing oral contraceptive) and 29 per 100,000 women years in women using
      gestodene containing oral contraceptive). Third-generation oral contraceptives
      induce a resistance to the activated protein C of almost the same magnitude as
      the resistance induced by a mutation in coagulation factor V. Studies with
      postmenopausal estrogen-replacement therapy show a two-fold risk of venous
      thromboembolism with estrogen only as well as with combined estrogen-progestagen
      hormone replacement therapy. However venous thromboembolism risk is very small
      compared with the cardiovascular and other benefits.

PMID- 9515143
TI  - [New causes of inherited thrombophilia].
AB  - Activated protein C resistance is the most frequent cause of thrombophilia. It is
      found in 20% of patients with an episode of deep vein thrombosis (DVT) and its
      prevalence in caucasian population is between 3-7%. Activated protein C
      resistance is secondary to an Arg 506 to Gln mutation of factor V (factor V
      Leiden). The relative risk of DVT for heterozygotes is 5 to 10, and for
      homozygotes 50 to 100. There is a 2- to 4-fold increase risk of recurrences in
      patients bearing the factor V Leiden mutation after a first episode of DVT.
      Recently a new mutation in the prothrombin gene (20210 G/A) was found to increase
      the relative risk of DVT by 2 to 4. Finally we also reviewed the association
      between DVT and hyperhomocysteinemia that is associated with a 2-fold increase
      risk of DVT.

PMID- 9515144
TI  - [Current data on the treatment of venous thromboembolic disease].
AB  - Venous thromboembolism disease is frequently seen in medical practice. Its
      morbidity, mortality and long-term sequels, as well as its haemorrhagic
      iatrogenic complications, represent a major problem of public health. For
      therapeutic management, we can usually use in medical practice non-fractionated
      heparin or low molecular weight heparin, sometimes substituted by antivitamin K
      therapy. Vena cava filter, surgical thrombectomy or thrombolytic therapy are
      rarely used. Elastic contention should by systematically prescribed. Therapeutic
      guidelines have been published on the recommendation furnished by randomised
      controlled trials. Low molecular weight heparin and early substitution by
      antivitamin K permitted an ambulatory treatment for deep vein thrombosis. The
      optimal duration of anticoagulant therapy is still controversial. Adequate
      biological survey causes decreasing incidence of haemorrhagic complications.

PMID- 9515145
TI  - [Current indications of cava filters].
AB  - Permanent vena cava filters are useful in venous thromboembolism in some rare
      medical situations (i.e., contra-indication or failure of anticoagulant therapy).
      Other indications are controversial. Indeed filters increase the risk of
      recurrence of deep vein thrombosis and also probably the incidence of post
      thrombotic syndrome. So filter placement remains a crucial decision, according to
      each individual case. The operator's choice is of prime importance. When a
      permanent filter is inserted the use of graded compression stockings and long
      term anticoagulant therapy deserves to be considered. In case of transient risk,
      temporary filters might be an interesting therapeutic approach but their
      assessment is insufficient in order for them to be currently recommended.

PMID- 9515146
TI  - [Cost of low molecular weight heparin used in the prevention or therapy of
      thromboembolic disease].
AB  - Low-molecular-weight heparin are widely used for prophylaxis or curative
      treatment of thromboembolic disease. In France, low molecular weight heparin can
      only be used for the surgical prophylaxis (general and orthopaedic) of
      thromboembolic disease, for the initial treatment of deep vein thrombosis and in
      haemodialysis. In an economic approach we try to assess costing information which
      takes account of drug acquisition costs but also costs of drug administration and
      costs of drug therapy failure (failed prophylaxis, bleeding and recurrent
      thrombosis). At least, it has been argued that low molecular weight heparin may
      take it possible to discharge patients earlier and even to treat patients at home
      or as out-patients, thus creating further cost savings.

PMID- 9515147
TI  - [Is the thermolabile variant of methylenetetrahydrofolate reductase a risk factor
      of arterial and venous thrombosis?].

PMID- 9515149
TI  - [Functional radionuclide imaging in cardiac failure].

PMID- 9515150
TI  - [Exercise test in the evaluation of cardiac failure].

PMID- 9515148
TI  - [Biological factors of the adaptation and non-adaptation of the myocardium to
      mechanical overstressing].

PMID- 9515151
TI  - [Are digitalis glycosides still integral part of the treatment of cardiac
      failure?].

PMID- 9515152
TI  - [Results of cardiac transplantation].

PMID- 9515153
TI  - [Cardiac failure: synthesis and future prospects].

PMID- 9515154
TI  - [Prostheses and pathology of GBM and CEDIT prostheses: from research to
      application].

PMID- 9515155
TI  - [Biodegradation of prosthesis materials. Induced pathology].

PMID- 9515156
TI  - [Infectious complications of cardiac valve prostheses].

PMID- 9515157
TI  - [Infections on joint prostheses].

PMID- 9515158
TI  - [Silicone breast prostheses: what about the supposed induced diseases?].

PMID- 9515159
TI  - [Granulomatous reactions and hip prosthesis. Anatomopathological aspects].

PMID- 9515160
TI  - [Complications of joint prostheses].

PMID- 9515161
TI  - Induction of apoptosis by an inhibitor of cAMP-specific PDE in malignant murine
      carcinoma cells overexpressing PDE activity in comparison to their nonmalignant
      counterparts.
AB  - In order to study potential changes in phosphodiesterase (PDE) activity
      associated with malignant transformation, normal primary keratinocytes and cells
      corresponding to different stages of epidermal tumor development in mouse skin
      were analyzed with respect to their 3',5'-cyclic adenosine monophosphate (cAMP)
      hydrolyzing activity. Expression of cAMP-specific PDE-4, intracellular cAMP
      content, and the sensitivity to the growth inhibitory effect of the PDE-4
      specific inhibitor 7-benzylamino-6-chloro-2 piperazino-4-pyrrolidino-pteridine
      (DC-TA-46) were studied in the two papilloma cell lines, MSCP6 and 308, and in
      the highly malignant carcinoma cell line CarB. No significant difference in
      soluble PDE activity and in intracellular cAMP was found in the two papilloma
      cell lines when compared to primary keratinocytes. In contrast, the spindle-cell
      carcinoma cell line CarB exhibited significantly higher PDE activity, concomitant
      with the lowest cAMP level. In all cell lines and also in the primary
      keratinocytes, rolipram-sensitive PDE-4 activity accounted for the major cAMP
      hydrolyzing activity. In primary keratinocytes and in MSCP6 cells, the PDE-4
      inhibitor DC-TA-46 induced at best marginal growth inhibition, whereas cell
      growth of 308 cells was markedly affected at concentrations > 2 microM. The
      carcinoma cell line CarB showed the highest sensitivity to DC-TA-46 (IC50 = 0.8
      +/- 0.3 microM). Treatment of CarB cells with DC-TA-46 strongly inhibits
      intracellular PDE activity, resulting in a marked and long-lasting rise of cAMP.
      After 24 h of treatment, arrest in the G0/G1 phase of the cell cycle is induced.
      Treatment with concentrations > 2 microM of this highly effective PDE inhibitor
      results in induction of apoptotic cell death, as detected by fluorescence
      microscopy, flow cytometry, and ELISA-based determination of fragmented DNA in
      intact cells.

PMID- 9515162
TI  - Differential distribution of rat PDE-7 mRNA in embryonic and adult rat brain.
AB  - Currently not much is known about the distribution and function of the
      phosphodiesterase type 7 (PDE-7) enzyme. Therefore, we carried out an extensive
      distribution analysis of the rat and human PDE-7 by in situ hybridization as well
      as RT-PCR. We isolated a partial rat cDNA clone that is highly homologous to the
      sequence of the human PDE-7 gene. RT-PCR tissue distribution analyses revealed
      expression of the mRNA of the human and rat-enzymes in most of the examined
      tissues, like adult heart, lung, brain, and liver, as well as in several cell
      lines of the immune system. In situ hybridization with the rat PDE-7 showed a
      differential expression pattern during the late phases of the developing rat
      brain with higher levels of mRNA in cortical and telencephalic structures in d
      16, 18, and 20 embryonic stages, whereas in adult rat brain, higher amounts of
      mRNA could only be detected in cerebellum and, to a lesser extent, in hippocampus
      and the olfactory system.

PMID- 9515163
TI  - Probing functional interfaces of rod PDE gamma-subunit using scanning fluorescent
      labeling.
AB  - In the dark, the activity of the rod cGMP phosphodiesterase (PDE) catalytic alpha
      and beta-subunits (P alpha beta) is inhibited by two gamma-subunits (P gamma).
      On light stimulation of the photoreceptor cells, the GTP-bound alpha-subunit of
      visual G-protein transducin (GtaGTP) displaces the P gamma-subunits from their
      inhibitory sites on P alpha beta, leading to the effect or enzyme activation. We
      designed a number of P gamma mutants, each with a single cysteine residue evenly
      distributed at a different position along the P gamma polypeptide chain. These
      cysteine residues served as sites for the introduction of the environmentally
      sensitive fluorescent probe, 3-(bromoacetyl)-7-diethyl aminocoumarin (BC).
      Analysis of the interactions of P alpha beta and Gta with the fluorescently
      labeled P gamma mutants suggests two distinct functional interfaces of P gamma.
      The P alpha beta/P gamma interface is formed essentially by the C-terminus of P
      gamma and by the N-terminal portion of the P gamma polycationic region, P gamma
      24-45, whereas the P gamma/Gta interface includes the C-terminal portion of P
      gamma-24-45 and the region surrounding P gamma Cys68. Such functional
      organization of P gamma may represent an important element for the PDE activation
      mechanism during transduction of visual signals.

PMID- 9515164
TI  - Expression and regulation of mRNA for distinct isoforms of cAMP-specific PDE-4 in
      mitogen-stimulated and leukemic human lymphocytes.
AB  - We reported previously that the gene for PDE-1B1 is induced in isolated human
      peripheral blood lymphocytes (HPBL) following mitogenic stimulation (Jiang, X.,
      Li, J., Paskind, M., and Epstein, P.M. [1996] Proc. Natl. Acad. Sci. USA 93,
      11,236-11,241). Using reverse transcription-polymerase chain reaction (RT-PCR),
      we investigated possible changes in the expression of the four genes for cAMP
      specific phosphodiesterase (PDE-4A-D) in HPBL under the same conditions.
      Isolated, quiescent HPBL express mRNA for PDE-4B as the principal transcript.
      Following mitogenic stimulation with phytohemagglutinin (PHA), mRNA for PDE-4A
      and PDE-4D are clearly induced. HPBL appear not to express PDE-4C under resting
      or stimulated conditions. The PHA induced increase in PDE-1B1, PDE-4A, and PDE-4D
      mRNA is mimicked by incubation of HPBL with dibutyryl cAMP (dBcAMP) and 1-methyl
      3-isobutylxanthine (IBMX). The B-lymphoblastoid cell line, RPMI 8392, and the T
      leukemic cell line, Molt 4, express PDE-4A mRNA as the most abundant transcript,
      but incubation with dBcAMP and IBMX induces an increase in the expression of mRNA
      for PDE-4B in both of these cell lines, and in PDE-4D3 in the RPMI 8392 cell
      line. These studies demonstrate that expression of mRNA for PDE-1B1 and some of
      the subtypes of PDE-4 are induced in HPBL following mitogenic stimulation,
      possibly secondarily to elevation of cAMP induced by the mitogen. As already
      indicated for PDE-1B1, some of these subtypes of PDE-4 might also provide
      additional therapeutic targets for treatment of immunoproliferative disorders and
      immune dysfunction.

PMID- 9515165
TI  - Upregulation of cAMP-specific PDE-4 activity following ligation of the TCR
      complex on thymocytes is blocked by selective inhibitors of protein kinase C and
      tyrosyl kinases.
AB  - We have previously shown that the major cAMP phosphodiesterase (PDE) isoforms
      present in murine thymocytes are the cGMP-stimulated PDE activity (PDE-2) and the
      cAMP-specific PDE activity (PDE-4), and that these isoforms are differentially
      regulated following ligation of the TCR (Michie, A.M., Lobban, M. D., Mueller,
      T., Harnett, M. M., and Houslay, M.D. [1996] Cell. Signalling 8, 97-110). We show
      here that the anti-CD3-stimulated elevation in PDE-4 activity in murine
      thymocytes is dependent on protein tyrosine kinase and protein kinase C (PKC)
      mediated signals as the TCR-coupled increase in PDE-4 activity can be abrogated
      by both the tyrosine kinase inhibitor, genistein, and the PKC selective
      inhibitors chelerythrine and staurosporine. Moreover, the PKC-activating phorbol
      ester, phorbol-12-myristate, 13-acetate (PMA) caused an increase in PDE-4
      activity, similar to that observed in cells challenged with anti-CD3 monoclonal
      antibodies and which was not additive with cochallenge using anti-CD3 antibodies.
      Both the PMA- and the anti-CD3 antibody-mediated increases in PDE-4 activity were
      blocked by treatment with either cycloheximide or actinomycin D. Despite the
      upregulation of PDE-4 activity consequent to TCR ligation, intracellular cAMP
      levels increased on challenge of thymocytes with anti-CD3 antibody, indicating
      that adenylate cyclase activity was also increased by TCR ligation. It is
      suggested that the anti-CD3-mediated increase in PDE-4 activity was owing to a
      rapid PKC-dependent induction of PDE-4 activity following crosslinking of the TCR
      complex. This identifies "crosstalk" occurring between the PKA and PKC signaling
      pathways initiated by ligation of the antigen receptor in murine thymocytes. That
      both adenylate cyclase and PDE-4 activities were increased may indicate the
      presence of compartmentalized cAMP responses present in these cells.

PMID- 9515166
TI  - Purification and physical characterization of cloned human cAMP
      phosphodiesterases PDE-4D and -4C.
AB  - Individual isozymes of family four cyclic-nucleotide phosphodiesterases (PDE-4s)
      were characterized and compared in order to advance our understanding of how PDE
      4s regulate cAMP levels in cells. Full-length and shorter clones containing
      various functional domains were constructed and overexpressed using a recombinant
      baculovirus-infected Sf9 insect cell system. One form each of PDE-4C and 4D was
      purified 125- and 534-fold, respectively, using anion-exchange and affi-gel blue
      chromatography. The purified material was unaltered in size on SDS-polyacrylamide
      gels during purification and nearly homogeneous (> 95%) as estimated by both
      staining and immunoblotting. Approximately 1 mg of PDE-4D (74.7 kDa) and 3.7 mg
      of PDE-4C (61.4 kDa) could be isolated from a 6-L culture of cells. The physical
      characteristics of Stokes' radius and sedimentation coefficient for PDE-4 enzymes
      cloned from each of the four isogenes were determined using size-exclusion
      chromatography and sedimentation in glycerol gradients. Calculations indicate
      that both long and short forms can form dimers, although evidence for monomers
      and higher-order subunit association was seen. Furthermore, the results clearly
      show that all long and short forms of PDE-4 are highly asymmetric molecules. This
      work has shown that large amounts of PDE-4 proteins can be purified and
      characterized physically and enzymatically to yield information that will enable
      a greater understanding of how PDE-4 enzymes function in cells.

PMID- 9515167
TI  - Correlations of PDE-4 inhibition between enzymes of smooth muscle and
      inflammatory cell sources.
AB  - The sensitivities of PDE-4 enzymes from smooth muscle and inflammatory cell
      sources from different species to a range of structurally diverse compounds were
      compared. All inflammatory cell PDE-4 sources displayed good crosscorrelations in
      their sensitivity to inhibition by these compounds. Similarly, PDE-4 enzymes from
      smooth muscle sources were well-correlated; however, there was no
      crosscorrelation between PDE-4 from smooth muscle sources and those of
      inflammatory cell sources, possibly reflecting differences in subcellular
      location of enzymes as well as subtype expression. The present study concludes
      that PDE-4 preparations from smooth muscle sources as well as those from
      inflammatory cell sources may be used to model the potential smooth muscle cell
      relaxing properties and anti-inflammatory properties of a compound in relation to
      human asthma.

PMID- 9515168
TI  - Compartmentalization of PDE-4 and cAMP-dependent protein kinase in neutrophils
      and macrophages during phagocytosis.
AB  - The compartmentalization of cAMP in human neutrophils during phagocytosis of
      serum-opsonized zymosan suggests that cAMP is an important second messenger for
      regulating phagocytosis. Type 4 cAMP-specific phosphodiesterase (PDE-4), cAMP
      dependent protein kinase (PKA), and adenylate cyclase are the principal effector
      molecules for cAMP regulation in phagocytes. Immunofluorescence microscopy
      demonstrated that PDE-4 isoforms (HSPDE-4A, HSPDE-4B, HSPDE-4D) were targeted to
      the forming phagosome in neutrophils, and were colocalized with the catalytic
      subunit of PKA and degranulated myeloperoxidase. Phagocytosis and accumulation of
      PDE-4 and PKA near adherent zymosan were inhibited by elevating cAMP levels with
      forskolin or rolipram. cAMP, PDE-4, and PKA were localized at sites of zymosan
      adherence in cells treated with cytochalasin D to inhibit phagosome formation,
      suggesting that zymosan engagement to Fc/CR3 receptors triggers cAMP elevations
      at sites of phagocytosis. HSPDE-4A, HSPDE-4B, HSPDE-4D, and PKA also were
      localized at the forming phagosome in monocyte-derived macrophages, and the
      lysosomal marker CD63 demonstrated the absence of PDE-4 around internalized
      phagolysosomes. These results suggest that cAMP levels are focally regulated by
      PDE-4 at the nascent phagosome, and that PKA may phosphorylate proteins
      associated with pseudopodia formation and phagosome internalization.

PMID- 9515169
TI  - Biology of metastatic disease.
AB  - Metastasis is highly organized and organ selective, a process involving multiple
      sequential steps. It occurs through complex interactions between tumor cells and
      the host. The surviving metastatic cells have heterogeneous biologic and
      antigenic or immunogenic properties, and the metastatic cells take over the
      homeostatic mechanisms of the host. Investigations at the genetic level are
      necessary to make advances in the early diagnosis, treatment, and prevention of
      metastatic disease.

PMID- 9515170
TI  - Evolution of the surgical management of pulmonary metastases.
AB  - Surgical treatment of pulmonary metastases dates back to the late 19th century.
      However, for the ensuing 50 years, the number of cases operated upon were few.
      Since the 1960s, the eligibility of patients for resection of pulmonary
      metastases has broadened. Neither the number of lesions nor the length of the
      disease-free interval excludes a patient from resection provided the primary
      tumor has been treated adequately and the patient can tolerate the resection.
      Resection of pulmonary metastases is predicated on the absence of effective
      treatment of nonoperative means and the ability to safely and completely resect
      all tumor and yet conserve sufficient lung tissue to provide a good quality of
      life. Major areas of controversy that remain are the number of metastases
      amenable to complete resection, the disease-free interval, the applicability by
      tumor type, and the role of chemotherapy. The data published to date suggest that
      pulmonary resection for metastases can improve overall survival with minimal
      morbidity and mortality.

PMID- 9515171
TI  - Imaging characteristics of metastatic disease to the chest.
AB  - The radiographic appearance of metastatic disease is classic, but nonspecific.
      The differentiating characteristics of radiographic patterns of metastatic
      disease are discussed in this article, as well as the relative advantages of
      different imaging modalities. Recommendations for radiologic evaluation are also
      presented.

PMID- 9515172
TI  - The role of endoscopy in the staging and management of lung metastases.
AB  - Endoscopic evaluation of the patient with lung metastases takes on many forms
      depending upon the extent of disease and the intent of treatment, be that
      curative or palliative. Thorascopy, and occasionally mediastinoscopy, may be
      helpful in assessing operability in patients with extensive disease on a
      preoperative computed tomography scan. However, when in doubt, exploration is
      always indicated in the young, good risk patient. Palliative efforts usually
      concern airway obstruction and malignant effects. A variety of technologies,
      including laser, brachytherapy, and endoluminal stents, helps manage symptomatic
      bronchial or tracheal lesions.

PMID- 9515173
TI  - The role of video-assisted thoracic surgery in pulmonary metastases.
AB  - The role of VATS in the management of patients with isolated pulmonary metastases
      is clear when performed for diagnostic purposes. In those patients with
      metastases that are too small for needle biopsy, when needle biopsy has been
      unsuccessful, or when more tissue is necessary for analysis, a VATS wedge
      resection can be performed with a high degree of success and minimal morbidity or
      inconvenience. The value of VATS for therapeutic resection of pulmonary
      metastases has not been demonstrated. Ideally, multicenter trials could address
      this issue along with the many unanswered questions concerning the fundamental
      concept of resection of pulmonary metastases.

PMID- 9515174
TI  - Osteosarcoma. Specific tumor management and results.
AB  - The survival rate of patients with osteogenic sarcoma has greatly improved with
      the institution of a multidisciplinary approach that combines multi-agent
      chemotherapy and limb-sparing surgery. Presently, 80% of those patients who do
      not have distant metastases at presentation will become long-term survivors,
      compared to 20% prior to 1970. For patients with metastases at diagnosis, or who
      develop metastases after initiation of treatment, long-term survival is also
      possible if all primary and metastatic disease is removed. The data presented in
      this article supports aggressive resection of pulmonary metastases in osteogenic
      sarcoma patients.

PMID- 9515175
TI  - Soft part sarcomas--metastases.
AB  - Pulmonary metastases may be resected safely with associated long-term survival.
      Regardless of histology, complete resection is associated with improved survival
      in most series. Various prognostic indicators may help clinicians select the
      optimal treatment for patients with pulmonary metastases. Novel treatment methods
      such as regional drug delivery or genetic manipulation may further enhance
      disease-free and overall survival.

PMID- 9515176
TI  - Current management of colorectal metastases to lung.
AB  - Colorectal carcinoma is the second most common visceral cancer in the United
      States, in both incidence and fatality rate. Of patients with colorectal
      carcinoma, 45% undergo resection and are cured. In cases of recurrence, 2% are
      restricted to lung only. A select group of 287 patients over 30 years at Memorial
      Sloan-Kettering Cancer Center underwent a surgical approach, which produced a
      survival rate of 40% at 5 years and 32% at 10 years.

PMID- 9515177
TI  - Kidney metastases.
AB  - Renal cell carcinoma is not common malignancy. Unfortunately, it remains
      difficult to cure, with small improvements being made in chemo/immunotherapeutic
      areas. Surgery remains the most successful approach for curative treatment in
      both primary and metastatic disease. Prospective studies are critically needed to
      definitively determine appropriate prognostic indicators for operation.

PMID- 9515178
TI  - Medical and surgical management of pulmonary metastases from germ cell tumors.
AB  - GCT is considered a curable tumor with a greater than 90% overall long-term
      survival. Pulmonary metastasis is common in patients with disseminated disease.
      First-line therapy in the management of patients with pulmonary metastases from
      germ cell tumors is cisplatin-based chemotherapy. Pulmonary metastasectomy has an
      important adjuvant role in a subset of patients who have residual radiographic
      abnormalities or progression of disease despite optimal chemotherapy. Surgical
      resection of residual pulmonary and mediastinal disease provides an accurate
      response assessment and consolidates the chemotherapy by removal of any viable
      GCT. Therefore, surgical resection of all residual masses is indicated in
      patients with NSGCT and normalized serum value of tumor markers after definitive
      systemic chemotherapy. Surgical resection or biopsy is a reasonable alternative
      in residual seminoma > or = 3 cm in diameter.

PMID- 9515179
TI  - Breast carcinoma metastases.
AB  - With careful selection of patients, complete resection of pulmonary metastases
      from breast carcinoma may be a useful therapeutic option. Such a treatment
      appears to offer a significant survival benefit when compared with medical
      treatment alone, or with incomplete resection.

PMID- 9515180
TI  - Isolated lung perfusion with antineoplastic agents for pulmonary metastases.
AB  - Lung metastases is a major cause of death in cancer patients. A technique of
      isolated lung perfusion that uses infusions of high doses of local chemotherapy
      was developed in an attempt to control local disease. This technique prevents
      systemic side effects. Animal experiments have been encouraging and human trials
      are pending.

PMID- 9515181
TI  - Surgical resection as the treatment of choice for melanoma metastatic to the
      lung.
AB  - Available data suggest that patients who have a limited number of pulmonary
      metastases may benefit from complete surgical resection if they have favorable
      prognostic features such as a long TDT and a long DFI. If a patient is not a
      surgical candidate because of radiographic evidence of extrapulmonary disease, a
      short TDT, or a short DFI, then concurrent or sequential biochemotherapy offers
      the best chance for a complete response and remission.

PMID- 9515182
TI  - A new staging proposal for pulmonary metastases. The results of analysis of 5206
      cases of resected pulmonary metastases.
AB  - In 1991, the International Registry of Lung Metastases was formed by 18 thoracic
      surgery departments in Europe and North America. Statistical analysis of combined
      data from the Registry revealed significant variables in patient selection, which
      helped to guide treatment modalities for specific patients. A simple system of
      stage classification is presented in this article as a basis for discussions on
      future results and for clinical trial design.

PMID- 9515183
TI  - Drug distribution. The forgotten relative in clinical pharmacokinetics.
AB  - The target concentration strategy has proved a valuable approach for dose
      individualisation, giving proper weight to the high interindividual variation in
      plasma concentrations. Nevertheless, optimisation of plasma concentrations does
      not necessarily yield optimal pharmacodynamic effects because variability in the
      plasma concentration-effect relationship is far from insignificant. We argue that
      this is due not only to unpredictable target tissue sensitivity but also to a
      highly variable, and equally unpredictable, distribution process from plasma into
      the interstitial space of the target tissue, the true effect compartment. This is
      borne out by recent results from studies employing modern techniques that enable
      direct measurement of target tissue drug concentrations, like magnetic resonance
      spectroscopy, single photon emission computed tomography, and tissue
      microdialysis. Such forthcoming results highlight the importance of the
      distribution process as a key factor determining drug response. Clinical
      pharmacology should seek an improved understanding of the biological determinants
      governing not only plasma but tissue drug concentrations.

PMID- 9515185
TI  - Clinical pharmacokinetics of fibric acid derivatives (fibrates).
AB  - Beginning with the description of clofibrate in 1962, derivatives of fibric acid
      (fibrates) have been used clinically to treat dyslipidaemias. Subsequently,
      gemfibrozil, fenofibrate, bezafibrate, ciprofibrate and long-acting forms of
      gemfibrozil, fenofibrate and bezafibrate have been developed. Clinically, this
      class of drugs appears to be most useful in lipoprotein disorders characterised
      by elevations of very low density lipoprotein and plasma triglycerides, which are
      often accompanied by reductions in high density lipoprotein (HDL) levels. The
      principal effects are a reduction in triglyceride and increase in HDL levels,
      with increases in the activity of hepatic lipase and lipoprotein lipase. There is
      some reduction of low density lipoprotein (LDL), lipoprotein (a), fibrinogen and
      uric acid. As a class, these drugs are generally well absorbed from the
      gastrointestinal tract (immediate-acting fenofibrate being the exception) and
      display a high degree of binding to albumin. Fibrates are metabolised by the
      hepatic cytochrome P450 (CYP) 3A4. All members of this class are primarily
      excreted via the kidneys and display some increase in plasma half-life in
      individuals with severe renal impairment. The long-acting forms of gemfibrozil
      and bezafibrate have pharmacokinetic properties similar to those of their
      immediate-acting parent compounds. The long-acting form of fenofibrate, produced
      by the process of micronisation, has increased oral bioavailability with less
      variability in absorption compared with the immediate-acting form of fenofibrate.
      Drug interactions are seen with other drugs that share a high degree of binding
      to albumin or are metabolised by CYP3A4. Clinically the most important and most
      commonly reported drug interactions are with HMG-CoA reductase inhibitors
      (lovastatin, simvastatin, pravastatin and fluvastatin), warfarin, cyclosporin and
      oral hypoglycaemic agents [including metformin, tolbutamide and glibenclamide
      (glyburide)]. The main potential for drug interactions is with drugs or compounds
      that are metabolised by or affect CYP3A4, including imidazoles, grapefruit juice,
      erythromycin, mibefradil and others.

PMID- 9515187
TI  - Pharmacokinetic optimisation of the treatment of cancer with high dose
      zidovudine.
AB  - The thymidine analogue zidovudine is currently used for the treatment of HIV
      infected patients, as the early development of the drug as an anticancer agent
      yielded modest results. A comprehensive preclinical analysis, however, showed
      that inhibitors of de novo thymidylate synthesis, including fluorouracil and
      methotrexate, enhanced the antiproliferative activity of zidovudine in cancer
      cells. Significant inhibition of tumour growth was obtained in mice bearing human
      colon cancer xenografts and given intraperitoneal zidovudine 300 to 600 mg/kg
      weekly in combination with methotrexate 87.5 mg/kg or intraperitoneal
      fluorouracil 85 mg/kg, and in pharmacokinetic studies high peak drug plasma
      concentrations (Cmax) of zidovudine were obtained, ranging from 610.3 to 1698.8
      mumol/L. In order to exploit the therapeutic activity of zidovudine, phase I and
      II clinical studies were designed in combination with fluorouracil and the
      pharmacokinetic-pharmacodynamic profile of zidovudine was investigated. Clinical
      responses were obtained in patients treated intravenously with bolus fluorouracil
      500 mg/m2, leucovorin and short (90 to 120 minutes) infusions of high dose
      zidovudine (up to 10 g/m2), generating drug Cmax similar to those obtained in
      preclinical models. However, in chemotherapy-pretreated patients receiving high
      dose zidovudine by the oral route (1 to 9 g/m2/day) or 48-hourly continuous
      intravenous infusion (2 to 20 g/m2/day) in combination with fluorouracil and
      leucovorin, treatment failures were observed despite high systemic exposure,
      described as the area under the plasma concentration-time curve and the
      occurrence of DNA strand breaks in peripheral blood mononucleated cells, the
      biological expression of zidovudine activity. In conclusion, preclinical and
      clinical evidence suggest that the schedule of administration of zidovudine is a
      requisite for the expression of its activity, indicating the importance of
      concentration-monitored trials to optimise chemotherapy dose administration in
      patients. The likelihood of tumour response appears to be related to the
      achievement of high peak plasma concentrations of zidovudine, and constant
      infusions appear less likely to produce clinical results.

PMID- 9515186
TI  - Pharmacokinetics and pharmacodynamics of estramustine phosphate.
AB  - Estramustine phosphate (estramustine phosphate sodium), a carbamate ester
      combining 17 beta-estradiol and nor-nitrogen mustard, is a cytotoxic drug used in
      the treatment of advanced prostatic carcinoma. Because of the radiosensitising
      effect of this drug there has been a recent increase in interest concerning
      estramustine phosphate and its clinical use. It has also been found that the
      early recommendations of drug administration together with food or milk were
      inappropriate, since calcium containing food and antacids hamper drug uptake.
      This may have obscured results from earlier clinical studies with estramustine
      phosphate. Estramustine phosphate is currently being re-evaluated for the
      treatment of other tumours such as glioma and mammary carcinoma. This review
      summarises the present relatively limited knowledge concerning the
      pharmacokinetic and pharmacodynamic aspects of estramustine phosphate and its
      metabolites.

PMID- 9515189
TI  - Using a quality of life measure to investigate outcome in outpatient treatment of
      severely impaired psychiatric clients.
AB  - Subjective quality of life (SQL) reports in mental health settings are used with
      increasing frequency despite some theoretical and psychometric concerns. The
      authors report on 1,291 SQL reports from two assessment/casework centers serving
      indigent mental health outpatients in the St. Louis Metropolitan area, and a
      subsample of 156 clients who reported their SQL at admission and 1 year later.
      Standardization data for these clients are presented, as well as information on
      SQL domains and the internal consistency of the scale. It was found that symptom
      and adjustment scales comprise close to 40% of the SQL scale variance. In the 1
      year follow-up subsample, the overall scale and six domains showed small but
      significant differences between admission and 1-year follow-up results.

PMID- 9515188
TI  - Long-term outcome of psychiatric disorders in the community: a 13-year follow-up
      study in a nonclinical population.
AB  - In 1980, a two-stage cross-sectional study on the prevalence of mental disorders
      was performed on a probability sample of 1,574 adult residents of two boroughs in
      Greater Athens served by a Community Mental Health Center (CMHC). After
      completion of the interviews, a "case" identification procedure was applied
      through the use of clinical criteria allocating each respondent to one of five
      categories ranging from "well" to definite "cases" (stage A). In stage B time 1
      (1980 to 1981), two psychiatrists interviewed a sample of 360 respondents
      consisting of all the probable and definite cases together with randomly selected
      individuals from the other three mental status categories. In 1994 (time 2), a
      follow-up study was conducted to reinterview the sample of 360 respondents
      through the use of the Structured Clinical Interview for DSM-III-R (SCID). The
      follow-up search resulted in 182 baseline respondents being located alive, plus
      38 certified as dead and a residual 140 (38.8% of the baseline sample)
      categorized as definitely unlocatable. We report results for the outcome of
      specific nosological entities over the 13-year period. Among the main findings,
      of the previously (1980 to 1981) identified cases, 42.8% were similarly diagnosed
      as cases in the follow-up study at time 2; 92.4% of the baseline stage B (1980 to
      1981) noncases were also found to be noncases in 1994. "Caseness" was found to be
      associated with high mortality. Of the subjects interviewed at both cross
      sections and diagnosed as having a psychiatric nosological entity at time 1 (1980
      to 1981), 67.5% were found to be mentally healthy at time 2 (1994).

PMID- 9515190
TI  - The high prevalence of "soft" bipolar (II) features in atypical depression.
AB  - Seventy-two percent of 86 major depressive patients with atypical features as
      defined by the DSM-IV and evaluated systematically were found to meet our
      criteria for bipolar II and related "soft" bipolar disorders; nearly 60% had
      antecedent cyclothymic or hyperthymic temperaments. The family history for
      bipolar disorder validated these clinical findings. Even if we limit the
      diagnosis of bipolar II to the official DSM-IV threshold of 4 days of hypomania,
      32.6% of atypical depressives in our sample would meet this conservative
      threshold, a rate that is three times higher than the estimates of bipolarity
      among atypical depressives in the literature. By definition, mood reactivity was
      present in all patients, while interpersonal sensitivity occurred in 94%.
      Lifetime comorbidity rates were as follows: social phobia 30%, body dysmorphic
      disorder 42%, obsessive-compulsive disorder 20%, and panic disorder (agoraphobia)
      64%. Both cluster A (anxious personality) and cluster B (e.g., borderline and
      histrionic) personality disorders were highly prevalent. These data suggest that
      the "atypicality" of depression is favored by affective temperamental
      dysregulation and anxiety comorbidity, clinically manifesting in a mood disorder
      subtype that is preponderantly in the realm of bipolar II. In the present sample,
      only 28% were strictly unipolar and characterized by avoidant and social phobic
      features, without histrionic traits.

PMID- 9515192
TI  - Patterns of short-term course in patients treated in a day unit for personality
      disorders.
AB  - The objectives of the study were (1) to explore differences in the course for
      patients treated in a day unit specializing in personality disorders (PDs), and
      (2) to determine characteristics of patients with different courses and
      predictors of various courses. K-mean cluster analysis was applied to partition a
      sample of 128 patients, 101 with various PDs and 27 with axis I disorders only,
      into four groups representing different courses. The course was defined on the
      basis of global functioning (Health Sickness Rating Scale [HSRS]) at admission,
      discharge, and 3-years follow-up evaluation. The four courses were labeled good,
      fair, late improvement, and poor, demonstrating great variation in the short-term
      course among patients with PDs. Predictors were studied by means of polychotomous
      logistic regression using the patients with a fair course as the reference group.
      The dichotomy no PD/cluster C versus cluster A/B predicted a good versus a fair
      course. A poor work status the last year before admission and irregular discharge
      predicted a poor or late improvement course versus a fair course, also when
      controlling for PD clusters. None of the included variables discriminated between
      patients with a poor versus late improvement course.

PMID- 9515191
TI  - Comorbidity of personality disorders with bipolar mood disorders.
AB  - The aim of the study was to assess the prevalence of personality disorders in a
      group of outpatients with bipolar I disorder. The Structured Clinical Interview
      for DSM-III-R Personality Disorders (SCID-II) was administered to 90 bipolar
      outpatients who met the DSM-III-R criteria and 58 control subjects. Of the
      patients and controls, 47.7% and 15.5%, respectively, had at least one
      personality disorder. At least one personality disorder in clusters A, B, and C
      and obsessive-compulsive, paranoid, histrionic, and borderline personality
      disorders were significantly more prevalent in bipolars. Suicide attempts were
      more frequent in patients with a history of personality disorder.

PMID- 9515184
TI  - Clinical pharmacokinetics of ibuprofen. The first 30 years.
AB  - Ibuprofen is a chiral nonsteroidal anti-inflammatory drug (NSAID) of the 2
      arylpropionic acid (2-APA) class. A common structural feature of 2-APANSAIDs is a
      sp3-hybridised tetrahedral chiral carbon atom within the propionic acid side
      chain moiety with the S-(+)-enantiomer possessing most of the beneficial anti
      inflammatory activity. Ibuprofen demonstrates marked stereoselectivity in its
      pharmacokinetics. Substantial unidirectional inversion of the R-(-) to the S-(+)
      enantiomer occurs and thus, data generated using nonstereospecific assays may not
      be extrapolated to explain the disposition of the individual enantiomers. The
      absorption of ibuprofen is rapid and complete when given orally. The area under
      the plasma concentration-time curve (AUC) of ibuprofen is dose-dependent.
      Ibuprofen binds extensively, in a concentration-dependent manner, to plasma
      albumin. At doses greater than 600mg there is an increase in the unbound fraction
      of the drug, leading to an increased clearance of ibuprofen and a reduced AUC of
      the total drug. Substantial concentrations of ibuprofen are attained in synovial
      fluid, which is a proposed site of action for nonsteroidal anti-inflammatory
      drugs. Ibuprofen is eliminated following biotransformation to glucuronide
      conjugate metabolites that are excreted in urine, with little of the drug being
      eliminated unchanged. The excretion of conjugates may be tied to renal function
      and the accumulation of conjugates occurs in end-stage renal disease. Hepatic
      disease and cystic fibrosis can alter the disposition kinetics of ibuprofen.
      Ibuprofen is not excreted in substantial concentrations into breast milk.
      Significant drug interactions have been demonstrated for aspirin (acetylsalicylic
      acid), cholestyramine and methotrexate. A relationship between ibuprofen plasma
      concentrations and analgesic and antipyretic effects has been elucidated.

PMID- 9515193
TI  - Critical comments made to schizophrenic patients by their families in Japan.
AB  - Critical comments (CCs) are one of the components of expressed emotion (EE), an
      excess of which is related to relapse. Therefore, CCs could be a target of family
      psychoeducation. We examined the nature of CCs for clues to family therapy. We
      classified CCs expressed in the Camberwell Family Interview (CFI) into nine
      categories: (1) positive symptoms, (2) negative symptoms, (3) compliance with
      medical care, (4) life problems, (5) socially inappropriate behavior, (6)
      aggression, (7) rejection, (8) premorbid personality, and (9) other. Positive
      symptoms were the most frequently commented on (34%). Negative symptoms were not
      so frequently commented on (11%), as expected. In comparing high-EE and low-EE
      relatives or relapsers and nonrelapsers, there were no significant differences in
      the distribution of the nine CC categories. We conclude that positive symptoms
      should be a main topic of family psychoeducation in such cases.

PMID- 9515194
TI  - Alexithymia: relationship with ego defense and coping styles.
AB  - There is controversy in the literature as to whether alexithymia reflects a
      deficit in the cognitive processing of emotions or a defensive coping style.
      Previous studies with clinical populations reported a strong association between
      alexithymia and a maladaptive (immature) ego defense style. The present study was
      designed to examine this relationship in nonclinical populations, and also to
      explore the relationships between alexithymia and three general styles for coping
      with stressful situations. Sample 1, 287 nonclinical adults, completed the Twenty
      Item Toronto Alexithymia Scale (TAS-20) and the Defense Style Questionnaire
      (DSQ). Sample 2, 83 undergraduate students who had been categorized previously
      into alexithymic and nonalexithymic subgroups, completed the DSQ and the Coping
      Inventory for Stressful Situations (CISS). In sample 1, the TAS-20 and its three
      factors were associated most strongly with an immature defense style, weakly with
      a neurotic defense style, and negatively with a mature defense style. In sample
      2, alexithymic students scored significantly higher than nonalexithymic students
      on the immature and neurotic defense factors of the DSQ and significantly lower
      on the mature defense factor. Alexithymic students also scored significantly
      higher on the emotion-oriented coping scale and the distraction component of the
      avoidance-oriented coping scale of the CISS and significantly lower on the task
      oriented coping scale. The results fail to support the view that alexithymia is
      an adaptive defense or coping style.

PMID- 9515195
TI  - Familial Mediterranean fever and the control of inflammation.

PMID- 9515196
TI  - Dendritic cells.
AB  - Dendritic cells are potent stimulators of immune responses against foreign
      antigens. Recent advances in this area include the delineation of distinct
      developmental pathways for different dendritic cell subsets; the emerging concept
      that one dendritic cell subset has regulatory functions that may contribute to
      induction of tolerance to self antigens; increased understanding of the
      interaction of dendritic cells with microbial products and viruses, such as HIV;
      and the application of dendritic cells for immunotherapy in certain cancers and
      possibly for the induction of transplantation tolerance.

PMID- 9515197
TI  - Fc gamma receptors in phagocytes.
AB  - Polymorphonuclear neutrophils, monocytes, and macrophages have numerous important
      functions in immunity, particularly the ingestion of antibody-coated
      microorganisms and cells. This review focuses on recent progress in the
      understanding of the family of receptors for the Fc end of IgG (Fc gamma R) on
      these phagocytes. The control of Fc gamma R expression, the cellular output
      signals from receptor engagement, and the basis of immediate and downstream
      signals in phagocyte activation are reviewed. Mice are increasingly being used in
      transgenic and knockout models of Fc gamma R biology. Relevant differences in the
      Fc gamma R endowments of mice and humans are detailed.

PMID- 9515198
TI  - Chronic graft-versus-host disease.
AB  - Chronic graft-versus-host disease (GVHD) continues to be the major problem in the
      long-term survivors of allogeneic hematopoietic stem cell transplants. Because of
      its similarities to autoimmune disease, the pathogenesis of chronic GVHD has been
      thought to differ from acute GVHD. Autoreactive T lymphocytes are an important
      effector mechanism with interferon gamma playing a central role in the increased
      collagen deposition that is the central histopathologic feature of chronic GVHD.
      Therapies that prevent the development of acute GVHD have been unsuccessful in
      the prevention of chronic GVHD. None of the present therapies for established
      chronic GVHD are successful in the majority of patients.

PMID- 9515199
TI  - Controversies in the treatment of neutropenia in cancer patients.
AB  - The supportive care of the neutropenic host is a complex problem and has been
      based primarily on the experience in cancer patients. The introduction of
      hematopoietic growth factors has been a major advancement, but further studies
      are needed to clarify their proper use in different clinical settings. In
      addition, the affect of growth factors-stimulated granulocyte transfusion will
      have to be defined. Together with a better understanding of different risk
      factors contributing to the risk of infection, the approach to treatment of the
      neutropenic patient will continue to evolve and hopefully permit more judicious
      use of antibiotic and growth factor therapies.

PMID- 9515200
TI  - Immune and idiopathic neutropenia.
AB  - Neutropenia is often attributed to immunologically mediated injury to mature
      neutrophils or their precursors. Clinically it is useful to classify immune
      mediated neutropenias as isoimmune, autoimmune (including some drug-associated
      neutropenias), and idiopathic (cases possibly with an immune mechanism).
      Isoimmune neutropenia occurs in infancy and the antigen and is an isoform of
      CD16. This condition usually resolves spontaneously. For other forms of immune
      neutropenia the antigens are not yet well defined and the diagnosis is usually
      based on clinical criteria. In these patients availability of granulocyte
      macrophage colony-stimulating factor is a major advance; most respond quickly to
      treatment with this growth factor.

PMID- 9515201
TI  - Recent advances in the pathogenesis and treatment of nonimmune neutropenias in
      the neonate.
AB  - Neutropenia in the neonate is defined as a significantly lower than normal
      concentration of neutrophils in the peripheral blood and can be broadly
      classified as immune or nonimmune. Nonimmune neutropenias are those that are not
      the direct or indirect result of antibodies directed against neutrophils. Recent
      advances have been made in the pathogenesis and treatment of several types of
      neonatal neutropenia, including reticular dysgenesis, Schwachman-Diamond
      syndrome, Kostmann syndrome, neutropenia in infants of hypertensive women, and
      "idiopathic neutropenia." This review of nonimmune neutropenias highlights these
      developments.

PMID- 9515202
TI  - Interleukin-6 in multiple myeloma and related plasma cell dyscrasias.
AB  - Since the discovery a decade ago that interleukin-6 is a growth factor for human
      multiple myeloma (MM) cells, great strides have been made in understanding the
      relationship of this cytokine to multiple myeloma. A plethora of studies on this
      topic has confirmed that interleukin-6 is a key growth and survival factor for
      myeloma cells, as well as a major morbidity factor for patients with MM. Their is
      strong evidence for both an autocrine (in MM cells) as well as a paracrine
      sources of interleukin-6 induction (from bone marrow stromal cells and osteoblast
      cells), with bone marrow stromal cells likely serving as the main center of
      production of interleukin-6 in patients with MM. Moreover, bone marrow stromal
      cells from patients with MM express viral interleukin-6, a functional homolog of
      human interleukin-6 that is produced by Kaposi's sarcoma-associated herpesvirus
      and may further enhance MM cell growth and survival. Soluble interleukin-6
      receptor serum levels are elevated in patients with MM; soluble interleukin-6
      receptor may amplify circulating interleukin-6 in patients with MM, and complex
      with interleukin-6, resulting in proliferation of MM cells that either express
      low or no detectable surface interleukin-6 receptor. Recent advances in our
      understanding of interleukin-6 signaling cascades mediating MM growth and
      survival, as well as its impact on cell cycle regulation in MM cells, may lead to
      therapeutics designed to interfere with these pathways. Finally, considerable
      progress has been made in identifying and developing agents including antibodies,
      biologic agents, hormones and drugs that interfere with the interleukin-6
      signaling pathways and may therefore have a role in the treatment of MM.

PMID- 9515203
TI  - Molecular biology of neutrophil differentiation.
AB  - Myeloid precursors undergo striking morphologic and functional changes during the
      process of granulocytic maturation. These changes are associated with significant
      changes in cell size and nuclear shape, and with the development of stage
      specific organelles which contain proteins necessary for the highly specialized
      roles of neutrophils in phagocytosis, in bacterial killing, and in mediating the
      inflammatory response. This complex process reflects a carefully regulated and
      sequential pattern of gene expression, which only recently has begun to be
      understood at the molecular level. The critical signals for the neutrophil
      differentiation program are postulated to derive from cytokines, and these
      cytokines are thought to induce a series of maturational events primarily by
      transcriptional regulation of sequentially expressed genes. Recent studies have
      identified a large number of transcriptional regulators, both positive and
      negative, that appear to act in concert in the developing neutrophil. These genes
      drive the complex and delicately timed sequence of genetic events that takes the
      cell from a progenitor to a functionally active neutrophil. Many of these genes
      are expressed throughout neutrophil differentiation, however, and the ongoing
      challenge is to elucidate how the function of these factors is modulated to allow
      the induction of sequential gene expression.

PMID- 9515204
TI  - Langerhans cell histiocytosis.
AB  - The term histiocytosis identifies a group of disorders characterized by localized
      or generalized reactive or neoplastic proliferation of cells similar, if not
      identical, to cells of the mononuclear phagocyte and dendritic cell systems. In
      Langerhans cell histiocytosis (LCH), the proliferating cell is the Langerhans
      cell, and the morphologic and immunohistochemical criteria for the definitive
      diagnosis of LCH have been established. The clinically evident pathology of LCH
      is broadly divided into two categories: direct involvement with the disease
      (e.g., lytic lesions of the bone or organ involvement) and secondary consequences
      resulting from permanent damage by the primary disease, LCH (eg, diabetes
      insipidus, fractures, and tooth loss). Current knowledge suggests tailoring the
      therapy to the extent of disease. Single-system disease can be treated by
      excisional biopsy, low-dose radiotherapy, or mild chemotherapy. Multisystem
      disease should be treated with combination chemotherapy, and current experimental
      therapeutic approaches include randomized treatment protocols for multisystem
      disease. A pressing current controversy regarding LCH is that its etiology is
      unknown. Whether LCH is reactive or neoplastic is even debated, and several
      features provide seemingly contradictory evidence on this point (spontaneous
      resolution of disease on one hand and clonality of lesional LCH cells on the
      other), underscoring the need for further studies to elucidate the etiology and
      pathogenesis of LCH.

PMID- 9515205
TI  - Antisense oligonucleotide therapeutics for human leukemia.
AB  - The development of reliable gene disruption strategies, and their application in
      living cells, has proven to be an extraordinary important advance for cell and
      molecular biologists. Using the various available approaches, the specific
      functions of any given gene may now be investigated directly in the relevant cell
      type. Application of similar experimental tools in a clinical setting might prove
      to be equally valuable and could well form the basis of a monumental advance in
      the practice of clinical medicine. This seems particularly true at the present
      time because much progress has been made in understanding the molecular
      pathogenesis of many diseases, including cancer. For these reasons a tremendous
      amount of interest has been generated in the use of oligodeoxynucleotides to
      modify gene expression. However, in spite of some notable successes which are
      detailed in this review, oligonucleotides have generated controversy in regard to
      their mechanism of action, reliability, and ultimate therapeutic utility.
      Nevertheless, the potential power of the "antisense" approach remains undisputed,
      and its ultimate therapeutic utility is far reaching. Accordingly, the problems
      associated with the use of these compounds are clearly worth solving. It remains
      the hope of many laboratories that the day will soon come when these techniques
      will make an important contribution to the management of chronic myelogenous
      leukemia and other neoplastic disorders.

PMID- 9515206
TI  - Macrophages and tuberculosis.
AB  - Almost one third of the world's population is infected with Mycobacterium
      tuberculosis (Mtb), the causative agent of tuberculosis. Each year there are
      eight million new cases of tuberculosis and three million deaths from the disease
      worldwide. Mtb is an intracellular pathogen that resides predominantly within
      macrophages. Paradoxically, macrophages also represent the first line of defense
      against this pathogen. Significant recent advances have been made in
      understanding the mechanisms by which Mtb gains entry into the macrophage,
      suppresses the microbicidal activities of this host cell, and ultimately subverts
      cell-mediated immune responses that eradicate the infection. This article reviews
      recent findings that contribute to our understanding of the roles played by
      mononuclear phagocytes in the immune response against tuberculosis.

PMID- 9515208
TI  - Leukocytes.

PMID- 9515207
TI  - New developments in hematopoietic stem cell expansion.
AB  - The possibility of maintaining, manipulating, and expanding human hematopoietic
      stem cells in ex vivo culture could help to provide patients with autologous and
      allogeneic stem cell transplants improved in purity and performance and could
      offer access to gene therapy of the hematopoietic system. Recent advances in the
      ex vivo culture of immature human hematopoietic progenitor cells and human
      hematopoietic stem cells have led to experimental evidence for the qualitative
      and quantitative maintenance and possible numerical expansion of hematopoietic
      stem cells in ex vivo culture, making ex vivo graft engineering a realistic
      possibility. This review summarizes recent developments in the field, their
      regulatory implications and their application in hematopoietic gene therapy.

PMID- 9515209
TI  - Cement injuries: Part I. Cement hand dermatitis resulting in "chrome cripples".

PMID- 9515210
TI  - Tinea versicolor: an update.

PMID- 9515211
TI  - Bullous pemphigoid in a previously irradiated site.
AB  - A 58-year-old woman who had previously undergone radiation therapy for breast
      cancer sustained bullous pemphigoid confined mainly to the radiation site.
      Radiation-induced bullous pemphigoid is an infrequently reported occurrence. This
      patient's lesions resolved within several weeks with combined oral therapy using
      tetracycline and niacinamide.

PMID- 9515212
TI  - Eczematous hypersensitivity from aqueous vitamin K injection.
AB  - Hypoprothrombinemic states are commonly treated with injectable vitamin K.
      Cutaneous vitamin K hypersensitivity can manifest as eczematous or sclerodermoid
      lesions and historically has been related to the use of fat-soluble vitamin K1.
      We present a case of warfarin-induced hypoprothrombinemia treated with aqueous
      vitamin K1, which resulted in the appearance of eczematous vitamin K1
      hypersensitivity.

PMID- 9515213
TI  - Gout in a patient with Reiter's syndrome.
AB  - A patient with coexistent Reiter's syndrome (RS) and tophaceous gout is
      described. The association of these two rheumatic diseases has not been
      previously reported. The reason for the rare association between gout and RS is
      unclear but possible explanations are reviewed. The diagnosis of gout should be
      considered in patients with RS who experience acute monoarticular or particular
      arthritis and characteristic cutaneous nodules.

PMID- 9515214
TI  - Localized crusted scabies of the scalp and feet.
AB  - An atypical case of crusted scabies in a patient with acquired immunodeficiency
      syndrome is presented in which lesions at the time of evaluation were confined to
      the scalp and feet. Because of the unusual presentation, the scalp involvement
      (which clinically mimicked seborrheic dermatitis) was initially missed. Although
      both the crusted variant of scabies and scabietic involvement of the scalp are
      well documented to occur in immunocompromised patients, to our knowledge scabies
      confined to the scalp and feet has not been previously reported.

PMID- 9515215
TI  - Lichen planus associated with hepatitis C.
AB  - The cause of lichen planus is unknown. Oral erosive lichen planus has been
      reported in association with liver disease. We describe a patient with chronic
      hepatitis C acquired through a blood transfusion with subsequent development of
      widespread hypertrophic lichen planus.

PMID- 9515216
TI  - Paraneoplastic pemphigus occurring in a patient with B-cell non-Hodgkin's
      lymphoma.
AB  - We present the case of a 71-year-old white male with paraneoplastic pemphigus
      associated with a B-cell non-Hodgkin's lymphoma. Diagnosis of paraneoplastic
      pemphigus was made by the characteristic findings on immunoprecipitation
      performed on a serum specimen. Paraneoplastic pemphigus is a severe autoimmune
      disease comprised of polymorphous mucocutaneous lesions, characteristic
      laboratory findings, association with one of several types of neoplasms, and a
      very poor prognosis.

PMID- 9515217
TI  - Pravastatin-induced lichenoid drug eruption.
AB  - Although drug eruptions caused by pravastatin and other lovastatin analogs have
      previously been described, reports of lichenoid eruptions are rare. We report a
      patient whose lichenoid lesions developed after initiation, resolved on
      discontinuation, and reappeared on rechallenge with pravastatin therapy. A brief
      review of lichenoid drug eruptions and skin lesions due to 3-hydroxy-3
      methylglutaryl coenzyme A reductase inhibitors is discussed.

PMID- 9515218
TI  - The frightful evolution from tubercle to mass.

PMID- 9515219
TI  - Phenytoin-induced verrucous eruption.

PMID- 9515221
TI  - Practical method for collecting nail plate specimens.
AB  - The use of a biopsy bag allows for the efficient collection of nail plate
      specimens. The bag functions as both a shield and net for the control and capture
      of nail clipping projectiles.

PMID- 9515220
TI  - Lichen planus and lichen sclerosus overlap.
AB  - Lichen planus and lichen sclerosus share several common features, including
      lymphocytic infiltration at the dermal-epidermal junction, clinical involvement
      of both skin and mucosa, erosive disease of mucosal surfaces, and the occasional
      occurrence of squamous cell carcinoma at the site of chronic, erosive mucosal
      lesions. In spite of these similarities, there are remarkably few reports of
      patients who concurrently have evidence of both diseases. We report a patient who
      had oral lesions of lichen planus and penile lesions of lichen sclerosus and we
      review possible mechanisms to explain this association.

PMID- 9515222
TI  - Itraconazole therapy in lymphocutaneous sporotrichosis: a case report and review
      of the literature.
AB  - A 24-year-old white man had a six-month history of nontender nodules on the
      dorsal aspect of the right hand. The lesions were diagnosed as lymphocutaneous
      sporotrichosis based on clinical appearance, histopathologic examinations, and
      fungal culture. Therapy with itraconazole was started. Considerable improvement
      was recorded after two months, when all of the lesions diminished in size and
      were no longer nodular in appearance.

PMID- 9515223
TI  - Phase I clinical trial of cefditoren pivoxil (ME 1207): pharmacokinetics in
      healthy volunteers.
AB  - Pharmacokinetics of ME1207 were evaluated in 5 groups of healthy adult male
      volunteers given single preprandial administration of 100, 200 and 300 mg;
      postprandial administration of 200 mg; and administration of 200 mg every 12 h
      for 7 consecutive days. Blood drug concentrations were determined by HPLC and
      bioassay after oral single administration of 100, 200 and 300 mg before meals.
      Serum concentrations and major pharmacokinetic parameters (Cmax, Tmax, AUC and
      T1/2 Ke) determined by these two methods were comparable. Cmax and AUC determined
      by bioassay after postprandial administration were greater than those determined
      after preprandial administration. Blood concentrations determined 1.5 and 12 h
      after each administration, during repeated administration of 200 mg every 12
      hours for 7 days, were always about 2.5 and 0 mg/l, respectively, indicating that
      the drug is not accumulated in the body. Within 24 hours after administration of
      100, 200 and 300 mg, 19.93 +/- 5.20, 20.24 +/- 3.72 and 21.29 +/- 5.47%,
      respectively, of the dose were excreted into urine in an unchanged form.

PMID- 9515224
TI  - Induction of flat morphology in K-ras-transformed fibroblasts by lycorine, an
      alkaloid isolated from the tropical plant Eucharis grandiflora.
AB  - In the course of screening for Ras function inhibitors from plant extracts, we
      isolated lycorine from a chloroform extract of Eucharis grandiflora leaves.
      Lycorine induced flat morphology in K-ras-NRK cells after treatment for 2-3 days,
      whereas its morphological effect on NRK cells was weaker. Lycorine was found to
      inhibit protein synthesis specifically in cultured K-ras-NRK cells. It also
      lowered the cellular amount of Ras in 2-3 days.

PMID- 9515225
TI  - Hydroxynimesulide, the main metabolite of nimesulide, prevents
      hydroperoxide/hemoglobin-induced hemolysis of rat erythrocytes.
AB  - The protective effect of hydroxynimesulide, the main metabolite of the
      nonsteroidal antiinflammatory drug nimesulide, on red blood cells (RBCs, 0.2%;
      3.5 x 10(7) cell/ml) hemolysis induced by cumene hydroperoxide (CuOOH; 50 microM)
      was evaluated by turbidimetric and morphological analyses. Hydroxynimesulide
      inhibits the CuOOH-induced hemolysis in a dose dependent fashion: the protective
      effect, calculated after 150 min incubation (100% hemolysis in the controls),
      starts at 1 micron (% hemolysis 85.2 +/- 3.4%) and increases at the higher
      concentrations (63.5 +/- 3.9% at 5 microM; 43.5 +/- 6.3% at 10 microM; and, 14.5
      +/- 4.3% at 20 microM). In addition, in the samples protected with 10 microM and
      20 microM, there is a significant delay (30 and 60 min) in the onset of the
      hemolytic response. Inhibition of hemolysis is the result of protection of RBC
      membrane integrity, both on lipid (cis-Parinaric acid fluorescence quenching was
      delayed by 53 +/- 10 sec vs. the controls at 1 micron, by 115 +/- 15 sec at 5
      microM, with a lag phase of 240 +/C- 18 sec at 10 microM) and protein
      constituents, as determined by SDS-PAGE electrophoresis. In hemolysis
      experiments, the efficacy of hydroxynimesulide is comparable to that of alpha
      tocopherol and a cooperative interaction between hydroxynimesulide and alpha
      tocopherol (both at 10 microM) has been observed. These results indicate that
      hydroxynimesulide protects RBC membranes by directly quenching reactive oxygen
      species generated by hemoglobin/peroxide interaction. Evidence for a direct
      radical scavenging intervention of the metabolite comes from HPLC studies, which
      demonstrate a time-dependent consumption of hydroxynimesulide, with the
      concomitant formation of two main reaction (addition/oxidation) products.

PMID- 9515226
TI  - The new immunosuppressants, the malononitrilamides MNA 279 and MNA 715, inhibit
      various graft-vs.-host diseases (GvHD) in rodents.
AB  - The use of inbred mouse strains of defined genetic background has allowed for the
      development of systems capable of reproducibly generating either an acute or
      chronic graft-versus-host disease (GvHD). The malononitrilamides MNA 279 and MNA
      715, analogues of the main metabolite of leflunomide, have been shown to directly
      inhibit T-cell proliferation and B-cell functions. Therefore, they have been
      studied in a local GvH reaction in the popliteal lymph node (PLN) assay in LBN
      rats, on the development of an acute and lethal GvHD in B6C3F1 mice and on a
      chronic autoimmune GvHD in BDF1 hybrid mice. In the PLN assay an oral
      administration of various concentrations (7.5 to 50 mg/kg) of both MNAs inhibited
      the localized GvH reaction dose-dependently and suppressed the lymph node
      hyperplasia. Both MNAs also acted therapeutically in this assay when they were
      given as late as day 4 or 5 after challenge. In the model of an acute lethal GvHD
      the treatment of the GvH-B6C3F1 hybrid mice with the MNAs (2.5 to 20 mg/kg/day)
      shortly after disease induction on days 3 to 12 resulted in a dose-dependently
      improved survival rate. With 20 mg/kg of drugs, mortality of this life
      threatening GvHD was completely prevented and also other parameters like
      splenomegaly, erythrocyte counts and hematocrit values were strongly suppressed.
      Treatment of sensitized GvH-BDF1 hybrid mice in the chronic autoimmune-like model
      with the MNAs (30 mg/kg/day), given on days 3 to 36 by oral gavage, resulted in
      an improved survival rate, inhibited lymphadenopathy and splenomegaly, reduced
      the levels of autoantibodies and other immunoglobulins like IgE and IgG1,
      prevented proteinuria and the development of glomerulonephritis. Both MNA 279 and
      MNA 715 can inhibit ongoing aberrant immune responses in animals suffering from
      GvHD.

PMID- 9515227
TI  - Therapeutic activity of malononitrilamides (MNA 279 and MNA 715) on acute and
      chronic, relapsing, experimental, allergic encephalomyelitis (EAE).
AB  - Due to their immunosuppressive mode of action, we examined the therapeutic
      effects of the malononitrilamides MNA 279 and MNA 715 in acute EAE, and two
      models of chronic relapsing EAE in Lewis rats and Biozzi mice. In the first
      model, sensitization of adult Lewis rats with guinea pig spinal cords results in
      an acute clinical episode of severe EAE, and by day 15 all animals had died.
      Treatment of these sensitized rats with the MNAs was most effective in delaying
      and reducing the onset of clinical symptoms, and mortality of acute EAE was
      prevented in a dose-dependent manner. The protection afforded by the two MNAs was
      long-lasting and no subsequent relapse was observed. Similarly, in the chronic
      relapsing disease, aged Lewis rats were immunized with rabbit myelin basic
      protein, and all untreated animals developed a disease with up to three relapses.
      The second and third episodes were both milder and shorter in duration than the
      first. All animals treated with the MNAs survived the first attack, which also
      was delayed. Pathological signs were reduced and relapses did not occur.
      Inhibition of chronic relapsing EAE in aged Lewis rats was observed, even when
      the MNA-treatment was started after the first appearance of clinical symptoms.
      All treated animals recovered completely and mortality was prevented. Also in the
      second model of chronic relapsing EAE in Biozzi AB/H mice, MNA treated animals
      showed only one acute and delayed episode and no further relapses. All these
      results qualify both MNA 279 and MNA 715 as powerful immunosuppressants with
      therapeutic potential in human multiple sclerosis (MS).

PMID- 9515228
TI  - Holding chambers for pMDI use.
AB  - Spacer devices for pressurized metered-dose inhalers (pMDI) are needed to slow
      down the aerosol jet and hence to reduce oropharyngeal deposition as well as to
      overcome coordination problems. A new spacer, JET (Chiesi, Italy), which is less
      cumbersome to carry, was tested on five healthy volunteers. They inhaled with a
      slow inspiratory vital capacity maneuver 2 x 100 micrograms doses of the beta 2
      agonist salbutamol, labelled with 99mTc, via a pMDI (Butovent, Chiesi) with and
      without the new JET spacer. The percentage of total delivered activity to the
      lungs increased with the JET from 14.3 +/- 4.5% to 22.3 +/- 4.1%, while the
      extrapulmonary deposition (oropharynx and stomach) was reduced from 39.8 +/-
      12.2% to 11.0 +/- 3.4%. These results show that the optimal application of the
      JET can improve therapeutic efficacy by reducing extrapulmonary drug deposition
      while increasing the drug delivery to the lungs. Use of holding chambers as
      reservoirs should be avoided as well as frequent cleaning of the spacer.

PMID- 9515229
TI  - Effects of a new platelet-activating factor antagonist, UR-12670, on several
      endotoxic shock markers in rats.
AB  - UR-12670 is a novel and potent PAF antagonist, eg., it displaces [3H]WEB-2086
      from PAF receptors in rabbit platelet membranes (Ki = 0.6 nM) and inhibits PAF
      induced increase in vascular permeability in rat trachea (100%), thymus (44%),
      seminal vesicles (100%) and stomach (54%) at a dose of 0.01 mg/kg i.v. Since PAF
      is thought to be an important mediator in endotoxic shock, the effect of
      pretreatment with UR-12670 on changes in vascular permeability, disseminated
      intravascular coagulation (DIC) and plasma biochemical parameters were determined
      in a rat model of acute endotoxemia. UR-12670 and the reference PAF antagonist,
      lexipafant (10 mg/kg i.v.), strongly inhibited lipopolysaccharide (LPS, 25 mg/kg
      i.v.)-induced plasma leakage in the trachea (49 and 100%, respectively) and
      seminal vesicles (81 and 100%), as assessed by the Evans blue extravasation
      method. Only lexipafant inhibited the increase in vascular permeability in the
      thymus (36%). Neither PAF antagonist was effective in the stomach. Both UR-12670
      and lexipafant at 10 mg/kg i.v. attenuated the LPS-induced variation of some DIC
      markers, such as activated partial thromboplastin time increase (56 and 58%,
      respectively) and the fibrinogen concentration decrease (53 and 31%), whereas the
      increase in prothrombin time was not affected. Increased plasma acid phosphatase
      (ACP, a lysosomal activation marker) and lactate dehydrogenase (LDH, a tissue
      damage marker) activity elicited by LPS was attenuated by pretreatment with 10
      mg/kg i.v. of either UR-12670 or lexipafant (ACP: 55 and 48%; LDH: 50 and 33%).
      LPS-induced hyperglycemia (46 and 37%) and hyperlactacidemia (100% both) were
      also inhibited. UR-12670 protected against several shock symptoms, confirming the
      role of PAF in the pathogenesis of rodent endotoxemia.

PMID- 9515230
TI  - Scolicidal agents in hydatid cyst surgery.
AB  - Injecting scolicidal solutions into the hydatid cyst and packing the operative
      field with sponges soaked in scolicidal agents have been used to avoid
      dissemination of the parasite during surgery. In the first part of this invitro
      study, we tried to determine the scolicidal property of various agents in
      different concentrations and exposure times. In the second part, we tested
      whether sponges soaked in different type and concentrations of scolicidal agents
      have any role beyond being a mechanical barrier. 20% saline, 3% hydrogen
      peroxide, 1.5% cetrimide-0.15% chlorhexidine (10% Savlon), 95% ethyl alcohol, 10%
      polyvinylpirrolidone-iodine (Betadine) and their further dilutions were used in
      this study. Protoscoleces were obtained from the cyst containing livers of the
      sheep and viability was determined with dye-uptake (0.1% Eosin) and flame cell
      activity. Savlon was found to be the least concentration dependent scolicidal
      agent among those studied. Scoleces sprayed on sponges soaked in 20% saline, 95%
      ethyl alcohol, Betadine and 3% hydrogen peroxide were killed after 15 minutes. 3%
      and 10% saline and normal saline were ineffective. Sponges work not only as a
      mechanical barrier but also as a chemical one if the agent is chosen correctly.
      In purely cystic hydatid liver disease, the risk of dissemination of the cyst
      contents can be avoided by injection of a potent scolicidal agent such as Savlon.

PMID- 9515231
TI  - The feasibility of laparoscopic cholecystectomy in patients with previous
      abdominal surgery.
AB  - A retrospective study was carried in 1500 patients submitted to elective
      laparoscopic cholecystectomy to ascertain its feasibility in patients with
      previous abdominal surgery. In 411 patients (27.4%) previous infraumbilical
      intraperitoneal surgery had been performed, and 106 of them (7.06%) had 2 or more
      operations. Twenty five patients (1.66%) had previous supraumbilical
      intraperitoneal operations (colonic resection, hydatid liver cysts,
      gastrectomies, etc.) One of them had been operated 3 times. In this group of 25
      patients the first trocar and pneumoperitoneum were performed by open
      laparoscopy. In 2 patients a Marlex mesh was present from previous surgery for
      supraumbilical hernias. Previous infraumbilical intraperitoneal surgery did not
      interfere with laparoscopic cholecystectomy, even in patients with several
      operations. There was no morbidity from Verres needle or trocars. In the 25
      patients with supraumbilical intraperitoneal operations, laparoscopic
      cholecystectomy was completed in 22. In 3, adhesions prevented the visualization
      of the gallbladder and these patients were converted to an open procedure. In the
      2 patients Marlex mesh prevented laparoscopic cholecystectomy because of
      adhesions to abdominal organs. We conclude that in most instances previous
      abdominal operations are no contraindication to laparoscopic cholecystectomy.

PMID- 9515232
TI  - Extrahepatic portal hypertension following liver transplantation: a rare but
      challenging problem.
AB  - This study reports our experience of 8 cases of extrahepatic portal hypertension
      after 273 orthotopic liver transplantations in 244 adult patients over a 10-year
      period. The main clinical feature was ascites, and the life-threatening
      complication was variceal bleeding. Extrahepatic portal hypertension was caused
      by portal vein stenosis in 6 patients, and left-sided portal hypertension in 2
      patients after inadventent ligation of portal venous tributaries or portasystemic
      shunts. All patients with portal vein stenosis had complete relief of portal
      hypertension after percutaneous transhepatic venoplasty (n = 4) or surgical
      reconstruction (n = 2), after a median follow-up of 33 (range: 6-62) months. Of
      the 2 patients with left-sided portal hypertension, one died after splenectomy
      and one rebled 6 months after left colectomy. This study suggests that
      extrahepatic portal hypertension is a series complication after liver
      transplantation that could be prevented by meticulous portal anastomosis and
      closure of portal tributaries or portasystemic shunts to improve the portal
      venous flow. However, any ligation has to be performed under ultrasound guidance
      to avoid inadventent venous ligations.

PMID- 9515233
TI  - Portal decompression using the inferior mesenteric vein.
AB  - We report five patients with variceal hemorrhage, in three cases secondary to
      diffuse thrombosis of the portal, superior mesenteric and splenic veins.
      Mesenteric angiography demonstrated patency of the inferior mesenteric vein (IMV)
      in each, and successful portal decompression by anastomosis of the IMV to the
      left renal vein (n = 4) or the inferior vena cava (n = 1) was accomplished.
      Bleeding was permanently controlled: four patients have survived from one to
      eight years post-operatively. Because shunt procedures utilizing the IMV are
      technically straightforward, subtotally decompress the portal system and avoid
      the right upper quadrant, they may be advantageous in certain clinical settings.

PMID- 9515234
TI  - An alternative technique in the treatment of celiac axis stenosis diagnosed
      during pancreaticoduodenectomy.
AB  - Celiac compression is usually a benign condition, but when surgery necessitates
      division of collaterals from the superior mesenteric artery, it may cause life
      threatening celiac organ ischemia. Celiac axis obstruction is found in 12.5% to
      49.7% of patients during abdominal angiography. In such patients, the arterial
      blood supply to the stomach, spleen, and liver is sustained through
      extraordinarily well-developed pathways in the pancreas. Though collateral
      pathways may be sacrificed during pancreaticoduodenectomy, only a small
      proportion of patients develop hepatic, gastric and splenic ischemia during the
      procedure. If the appropriate angiographic studies have not been obtained before
      pancreatic resection, a test occlusion of the gastroduodenal artery, as
      recommended by Bull et al., should precede its ligation. The hepatic arteries are
      palpated before and after the test occlusion. In the occasional patient in whom
      the pulse diminishes during occlusion or if there is evidence of upper abdominal
      visceral ischemia, revascularization of the celiac circulation may be required.
      Reestablishment of the celiac circulation may be accomplished by the use of a
      vein graft between the aorta and the celiac tributaries. This article describes
      an alternative technique for revascularization of the celiac circulation without
      the use of a venous graft.

PMID- 9515236
TI  - Cystic dilation of extrahepatic bile ducts in adulthood: diagnosis, surgical
      treatment and long-term results.
AB  - To evaluate the long-term results of surgery for choledohal cyst in adulthood, a
      series of 13 patients over the age of 16 operated on for choledochal cyst during
      a period of six years and followed-up for a minimum of 3 years was analyzed.
      Patients with type I and IVa cysts underwent extrahepatic cyst resection and Roux
      en-Y hepatico-jejunostomy. Choledochoceles (type III) were managed
      endoscopically. No operative mortality or morbidity occurred. Type I and III
      cysts showed almost ideal follow-up with no sign of stricture on HIDA scan. One
      type IVa cyst patients developed recurrent cholangitis due to anastomotic
      stricture, managed percutaneously. Whenever possible, complete cyst resection and
      Roux-en-Y reconstruction is the treatment of choice for all extrahepatic biliary
      cysts. Intra- and extrahepatic dilatations are adequately treated by extrahepatic
      resection and careful endoscopic or radiologic surveillance. Small
      choledochoceles can be safely managed by endoscopic sphincterotomy.

PMID- 9515235
TI  - External biliary fistula.
AB  - We report 210 cases of external biliary fistula treated in our clinics between
      1970-1992. In 7 cases, fistulas were formed after iatrogenic bile duct injury, in
      4 cases after exploration of common bile duct, in 4 cases due to disruption of
      biliary-intestinal anastomosis, and in 2 cases due to liver trauma. In 85 cases
      bile leak was observed after cholecystomy, in 103 cases after hydatid disease
      surgery, and in 4 cases after the passage of P.T.C. catheter. In one patient the
      appearance of the fistula was due to spontaneous discharge of a gallbladder
      empyema. 173 cases were managed conservatively, and 37 cases surgically.

PMID- 9515238
TI  - Surgical treatment for biliary carcinoma arising after pancreatoduodenectomy.
AB  - The clinicopathological features and surgical treatment of biliary carcinoma
      around the major hepatic duct confluence arising after pancreatoduodenectomy (PD)
      due to initial bile duct carcinoma are described in three patients. Occurrence of
      biliary carcinoma more than 12 years after initial surgery and a histological
      finding of cholangiocellular carcinoma mixed with hepatocellular carcinoma
      suggested metachronous incidence of biliary carcinoma after PD. Extended right
      hemihepatectomy with complete removal of the residual extrahepatic bile duct and
      segmental resection of the jejunal loop were carried out safely without operative
      death or severe postoperative complications. Two patients died of tumor
      recurrence 6 months after surgery, and the remaining patient is currently living
      a normal life without evidence of recurrence 17 months after surgery. These
      surgical procedures are a therapeutic option in patients with biliary carcinoma
      around the major hepatic duct confluence arising after PD.

PMID- 9515237
TI  - The role of oxygen free radicals in acute renal failure complicating obstructive
      jaundice: an experimental study.
AB  - Oxidant injury is considered to be an important mechanism in the pathophysiology
      of acute renal failure. It has been thought that decrease in extracellular and
      intracellular fluid and endotoxemia seen in obstructive jaundice may cause an
      increase in production of oxygen free radicals and impairment in antioxidant
      defense mechanism. This study is designed to investigate the possible role of
      oxidant injury in renal failure seen in jaundiced patients. In this study, 28
      rats were divided into four groups: Control (C)(N = 7); Renal ischemia (RI)(N =
      7); Obstructive jaundice+renal ischemia (OJ+RI)(N = 7); Obstructive jaundice
      (OJ)(N = 7). All groups were compared with each other according to renal failure
      findings and enzyme activities, such as Xanthine oxidase (XOD), Superoxide
      Dismutase (SOD) and Catalase in renal cortex and Glutathione Peroxidase (GSH-Px),
      in blood at 3rd day after ischemia and reperfusion. Renal failure findings
      monitored by blood urea and creatinine levels, seemed more evident in OJ+RI than
      RI group (p < 0.05). When compared with RI, in OJ+RI group, increase in XOD
      activity at 3rd day was statistically significant [0.259 +/- 0.01 U/g (tissue)
      and 0.362 +/- 0.03 U/g (tissue) respectively] (p < 0.05). SOD and GSH-Px
      activities of each ischemic group at 3rd day were decreased compared to non
      ischemic groups. This fall was significant (p < 0.05). But there was no
      statistical difference between jaundiced and non-jaundiced groups. Alterations in
      catalase activities also had no statistical significance. These findings may
      suggest that the injury induced by oxygen free radicals at re-oxygenation of
      tissue after ischemia may also play a role in the pathogenesis of acute renal
      failure developed in obstructive jaundice.

PMID- 9515239
TI  - Endoscopic and surgical management of a Hayes type III-G cystic duct anomaly
      causing a Mirizzi type I syndrome.

PMID- 9515240
TI  - Is chemoembolisation of value in inoperable primary hepatocellular carcinoma.
AB  - Chemoembolisation has been extensively used as primary treatment for unresectable
      hepatocellular carcinoma (HCC). In this unit, 185 patients with a new diagnosis
      of HCC not amenable to surgery were seen between 1988 and 1991. Intended therapy
      for these patients was chemoembolisation with doxorubicin (60 mg/m2) and
      lipiodol, repeated at six week intervals until it was technically no longer
      possible or until complete tumour response had been obtained. Chemoembolisation
      was possible in 67 of the 185 (37%). Reasons for exclusion were portal vein
      occlusion (n = 36), decompensated cirrhosis (n = 44), distant metastases (n = 5),
      diffuse tumour or unsuitable anatomy (tumour or vasculature) (n = 11), patient
      refusal (n = 11), and other (n = 11). Patients excluded from treatment survived
      for a median of 10 weeks (range 3 days-19 months). In patients treated, 18 had
      small HCC (4 cm) and 49 had large or multifocal HCC. Chemoembolisation was
      carried out a median of two sessions for small and three sessions for large
      tumours. Ten of 18 patients with small HCC showed a 50% or greater reduction in
      tumour size. Five of 49 patients with large or multifocal tumours showed a
      response to treatment. Median overall survival for treated patients was 36 weeks
      (range 3 days-4 years). One patient has subsequently undergone liver
      transplantation with no recurrence and minimal residual disease at
      transplantation. Two other patients are alive three years after
      chemoembolisation, one with no evidence of recurrent disease. No patient was
      thought suitable for surgery after their response to chemoembolisation.
      Chemotherapy related complications were seen in 22%. Complications were
      significantly more common in patients with larger tumours and poor liver reserve.
      Five patients died as a result of chemotherapy related complications. In
      conclusion, only one third of UK patients with unresectable HCC are treatable by
      chemoembolisation. Results with small tumours are encouraging, with a high
      response rate and the possibility of surgical intervention in previously
      inoperable disease. Large tumours, however, show a poor response and significant
      incidence of side effects, suggesting that this treatment offers little benefit
      in advanced disease.

PMID- 9515241
TI  - Bile duct calculi--the new challenges.
AB  - BACKGROUND: Morbidity and mortality after surgical treatment of bileduct stones
      increase with age and associated diseases. A proposed alternative therapy is
      endoscopic sphincterotomy (ES) with the gallbladder left in situ, and we elected
      to compare this option with standard open surgery in high-risk patients. METHODS:
      98 patients (mean age 80 years) with symptoms likely to be due to bileduct stones
      or a recent episode of biliary pancreatitis were randomised to be treated either
      by open cholecystectomy with operative cholangiography and (if necessary)
      bileduct exploration (n = 48) or by endoscopic sphincterotomy alone (n = 50).
      FINDINGS: The procedure was accomplished successfully in 94% of the surgery group
      and 88% of the ES group, and there were no significant differences in immediate
      morbidity (23% vs 16%) or mortality (4% vs 6%). During mean follow-up of 17
      months biliary symptoms recurred in three surgical patients, none of whom
      underwent repeat surgery, and in 10 ES patients, seven of whom had biliary
      surgery. By multivariate regression analysis endoscopic sphincterotomy was an
      independent predictor of recurrent biliary symptoms (odds ratio 6.9; 95% Cl 1.46
      to 32.54). INTERPRETATION: In elderly or high-risk patients, surgery is
      preferably to endoscopic sphincterotomy with the gallbladder left in situ as a
      definitive treatment for bileduct stones or non-severe biliary pancreatitis.

PMID- 9515242
TI  - Changing therapy for gastrinoma.
AB  - OBJECTIVE: The author analyzed potential survival determinants in gastrinoma to
      characterize a possible uniform staging system and to determine whether complete
      surgical resection improves expected survival. SUMMARY AND BACKGROUND DATA:
      Gastrinoma is an indolent yet malignant neuroendocrine tumor. The associated
      gastric acid hypersecretion can be controlled medically. Staging of gastrinoma is
      inconsistent and the role of surgical resection controversial. METHODS: Seventy
      four patients with gastrinoma with a minimum 5-year follow-up were assessed.
      Cox's proportional hazards regression model was used to examine the association
      of risk factors with survival. RESULTS: The following factors had no effect on
      survival: age at diagnosis, sex, presence of lymph node metastases, associated
      multiple endocrine neoplasia, and method of ulcer treatment. The three unique
      determinants of survival were primary tumor size (relative risk, 1.534; p =
      0.0005), liver metastases (relative risk, 2.947; p = 0.0209), and complete
      surgical resection (relative risk, 0.163; p = 0.0076). On the basis of these risk
      factors, a uniform staging system is proposed and predictive survival curves
      developed. CONCLUSIONS: The primary determinants of survival in gastrinoma are
      the size of the primary tumor and liver metastases. Complete surgical resection
      reduces mortality, regardless of other factors.

PMID- 9515243
TI  - Small-diameter PTFE portosystemic shunts: portocaval vs mesocaval.
AB  - Fifty-seven patients with failed sclerotherapy received a mesocaval interposition
      shunt with an externally supported, ringed polytetrafluoroethylene prosthesis of
      either 10 or 12 mm diameter. Thirty-one patients had Child-Pugh grade A disease
      and 26 grade B; all had a liver volume of 1000-2500 ml. Follow-up ranged from 16
      months to 6 years 3 months. Three patients (5 per cent) died in the postoperative
      period. There were two postoperative recurrences of variceal haemorrhage and one
      recurrent bleed in the second year after surgery. The cumulative shunt patency
      rate was 95 per cent and the incidence of encephalopathy 9 per cent; the latter
      was successfully managed by protein restriction and/or lactulose therapy. The
      actuarial survival rate for the whole group at 6 years was 78 per cent, for those
      with Child-Pugh grade A 88 per cent and for grade B 67 per cent. Small-lumen
      mesocaval interposition shunting achieves portal decompression, preserves
      hepatopetal flow, has a low incidence of shunt thrombosis, prevents recurrent
      variceal bleeding and is not associated with significant postoperative
      encephalopathy.

PMID- 9515244
TI  - Resection of hilar cholangiocarcinoma.
AB  - OBJECTIVE: Morbidity and mortality involved in the resection of hilar
      cholangiocarcinoma were reviewed retrospectively. The clinicopathologic and
      laboratory parameters that might influence the patient's survival also were re
      evaluated. SUMMARY BACKGROUND DATA: Although much progress has been made in the
      diagnosis and management of hilar cholangiocarcinoma, long-term outlook for most
      patients remains poor. Surgical resection is usually prohibited because of its
      local invasiveness, and most patients can only be managed by palliative drainage.
      Recently, many surgeons have adopted a more aggressive resection with varying
      degrees of success. Several prognostic factors in bile duct carcinoma have been
      proposed; however, no reports have specifically focused on resected hilar
      cholangiocarcinoma and its prognostic survival factors using multivariate
      analysis. METHODS: The clinical records and pathologic slides of 49 cases with
      resected hilar cholangiocarcinoma were reviewed retrospectively. Twenty clinical
      and laboratory parameters were evaluated for their correlation with postoperative
      morbidity and mortality, whereas 31 variables were evaluated for their
      significance with postoperative survival. Variables showing statistical
      significance in the first univariate analysis were included in the following
      multivariate analysis using stepwise logistic regression test for factors
      affecting morbidity and mortality and Cox stepwise proportional hazard model for
      factors influencing survival. RESULTS: There were 5 in-hospital deaths, and the
      cumulative 5-year survival rate in 44 patients who survived was 14.9%, with a
      median survival of 14.0 months. Multivariate analysis disclosed that coexistent
      hepatolithiasis and lower serum aspartate aminotransferase levels (90 U/L) had a
      significant low incidence of postoperative morbidity, whereas a serum albumin of
      less than 3 g/dL was the only significant factor affecting mortality. Regarding
      survival, univariate analysis identified eight significant factors: 1) total
      bilirubin 10 mg/dL, 2) curative resection, 3) histologic type, 4) perineural
      invasion, 5) liver invasion, 6) depth of cancer invasion, 7) positive proximal
      resected margin, and 8) positive surgical margin. However, multivariate analysis
      disclosed total bilirubin > or = mg/dL, curative resection, and histologic type
      as the three most significant independent variables. CONCLUSIONS: Surgical
      resection provides the best survival for bilar cholangiocarcinoma. An adequate
      nutritional support to increase serum albumin over 3 g/dL is the most important
      factor to decrease postoperative mortality. Moreover, preoperative biliary
      drainage to decrease jaundice and a curative resection with adequate surgical
      margin are recommended if longer survival is anticipated. Patients with well
      differentiated adenocarcinoma seem to survive longer compared to those with
      moderately or poorly differentiated tumors.

PMID- 9515245
TI  - [Tetralogy of Fallot in the neonate. Surgical repair or palliation?].

PMID- 9515246
TI  - [Clinical course of patients treated with partial left ventriculectomy].
AB  - OBJECTIVE: To assess the efficacy of partial left ventriculectomy as a treatment
      for patients with end-stage heart failure. METHODS: From February to June 1995, 7
      patients with end-stage heart failure underwent partial left ventriculectomy.
      Subsequently, patients underwent clinical evaluation every 2 months, and 2
      dimensional echocardiography at the 6th and 12th months after cardiac surgery.
      All patients were given digitalis and diuretics at conventional doses, and
      captopril or enalapril at maximal tolerated doses. RESULTS: Two (28%) patients
      died; 1 from cardiac arrhythmia associated with gastrointestinal hemorrhage, and
      the other suddenly. One (14%) patient developed an embolic cerebrovascular
      accident. Four (57%) patients were hospitalized for congestive heart failure; all
      of them had either decreased the daily dose of captopril or enalapril or
      discontinued the drugs by themselves. Twelve months after ventriculectomy, left
      ventricular ejection fraction values were greater and left ventricular diastolic
      dimension and functional class values lower than those found before cardiac
      operation. CONCLUSION: Beneficial effects of partial left ventriculectomy are
      observed one year after the surgical procedure. This technique, therefore, can be
      useful for the treatment of patients with end-stage heart failure.

PMID- 9515248
TI  - [Clinical profile of aged patients with severe aortic stenosis].
AB  - PURPOSE: To evaluate clinical symptoms and echocardiographic findings in elderly
      patients with severe aortic stenosis and possible gender differences. METHODS: We
      studied 54 patients, 24 (44.5%) males and 30 (55.5%) females aged 80.7 +/- 5.2
      years with severe aortic stenosis. The following variables were analyzed:
      presence of clinical manifestations (dyspnea, angina, and syncope) and
      echocardiographic indices (left ventricular [LV] dimensions, ejection fraction
      [EF], and mass index). RESULTS: Dyspnea was the most frequent symptom with
      overall prevalence of 44%. EF was lower than 50% in only 2 patients. There were
      no gender differences in the prevalence of any of the clinical manifestations.
      Male patients had higher LV volumes (p < 0.05) and lower EF (p = 0.03).
      CONCLUSION: The data showing dyspnea as the most common clinical manifestation;
      EF > 50%; lower LV volumes and greater EF in female patients suggest that the
      adaptive mechanisms to this condition may be different between the two sexes.

PMID- 9515247
TI  - [Diagnostic accuracy of dobutamine-atropine stress echocardiography].
AB  - PURPOSE: To analyze the diagnostic accuracy of dobutamine-atropine stress
      echocardiography. METHODS: We studied 304 consecutive patients using dobutamine
      atropine stress echocardiography who underwent coronary angiography within a
      month of the exam. Patients received high dobutamine doses associated or not with
      atropine. RESULTS: The global sensitivity was 92%, specificity was 72% and
      diagnostic accuracy was 87%. Analyzing 120 patients with normal LV function, we
      found sensitivity of 85%, specificity of 79% and accuracy of 82%. CONCLUSION:
      Dobutamine-atropine stress echocardiography is an accurate method for the
      detection of coronary artery disease.

PMID- 9515249
TI  - [Quality of life after surgical correction of the aorta coarctation.
      Retrospective analysis of a group of patients with long-term follow-up].
AB  - PURPOSE: To report on the long-term results after operation for coarctation of
      the aorta. METHODS: One hundred and four patients were studied, divided in four
      groups (G1, G2, G3 and G4), according to age at operation. Data analysed:
      reoperation, persistent hypertension, residual lesions, left ventricular function
      and ability index. RESULTS: Reoperation was frequent, mainly in G1 (60%) and G4
      (29%). Resting hypertension occurred predominantly in cases operated on after the
      10th year of life: 28% (G3) and 29% (G4). Exercise hypertension was found in
      cases operated on after the 20th year. Residual lesions were frequent: 97%, 98%,
      83% and 65% (G1 to G4). Individual functional limitation was uncommon. The
      ability index was normal in the great majority of the patients (94%). CONCLUSION:
      Reoperation is frequent, particularly for recoarctation and aortic stenosis. Rest
      and/or exercise hypertension is common and related to delayed surgery. Aortic
      residual lesions are frequent. Physical limitation is uncommon. Postoperative
      follow-up is essential in order to detect late complications, which, usually, do
      not limit the individual patient.

PMID- 9515250
TI  - [Treatment of femoral false aneurysms following cardiac catheterization with
      compression and color Doppler echocardiography monitoring].
AB  - PURPOSE: To evaluate the efficiency of a non-surgical treatment of the femoral
      false aneurysm following cardiac catheterization using the color Doppler
      echocardiography monitorization. METHODS: From August 1993 to October 1996, 17
      patients were evaluated by the color Doppler echocardiography, 7 women and 10
      men, between 58 and 77 years of age, with the diagnosis of femoral false
      aneurysms after cardiac catheterization. All the cases were selected for therapy
      with this new technique, that consisted of the compression of the false aneurysm
      with the transducer of the ultrasound device and monitorization of the evolution
      of the false aneurysm thrombosis, through image observation in real time, on the
      equipment monitor. RESULTS: There were 17 selected patients, 16 were successfully
      treated, requiring an average of 30 minutes of compression with consequent
      thrombosis of the false aneurysm, without recurrence in 30 days of follow-up. No
      complications with the use of this technique were noted and the hospitalization
      period was, on average, 1 day. CONCLUSION: This technique is efficient, safe and
      should be the first choice for the therapy of patients with femoral aneurysm
      following cardiac catheterization.

PMID- 9515251
TI  - [Blood pressure measurement. Criteria employed in scientific articles published
      in Brazilian journals].
AB  - PURPOSE: To evaluate the criteria used for the technique of blood pressure
      measurement in scientific articles published in Brazilian journals. METHODS: Two
      hundred twenty three scientific articles from 18 medical journals, published
      between 1989 and 1994 were evaluated, in order to identify the type of
      sphygmomanometer used; the state of calibration; the cuff size; the position of
      the patient during the measurement; whether the blood pressure measurement was
      obtained after a resting period; the phase used to identify the systolic and
      diastolic pressures; and the number of readings taken. RESULTS: There was no
      reference in the articles about the following data: the type of sphygmomanometer
      in 51%, the accuracy of calibration in 82%, the cuff size in 64%, the position of
      the patient in 25%, the rest period before measurement in 60%, the systolic and
      diastolic phases in 49%, and the number of measurements in 52%. CONCLUSION: Most
      of the papers analyzed did not follow or omitted important aspects cited in
      national and international recommendations for the correct blood pressure
      measurement.

PMID- 9515252
TI  - [Race, compliance to treatment and/or consultation and control of arterial
      hypertension].
AB  - PURPOSE: To compare racial differences on hypertension (Hy) control and
      compliance to appointments and/or treatment. METHODS: Between November/94 to
      January/95, 200 low social strata hypertensive outpatients were interviewed
      (cross-sectional clinical-epidemiologic study) and had their blood-pressure
      measured (double-blind) in Salvador, Brazil. Compliance to treatment criteria: >
      or = 50% appointments/year; compliance to treatment = Hy control-WHO and NIH
      criteria. Means, frequency ratios (FR) and chi 2 were used in the analysis.
      RESULTS: Most of the hypertensives (88%) were women. Race: 45.5% were mulatoes
      (M) and 40.5% blacks (B). Compliance to appointments and treatment (A + T) was
      30.5%, to treatment (T) 11%, to appointments, 37%, and noncompliance = 21.5%.
      Compliance was 53.6% for whites (W) and 19.7% for B (p < 0.001); 40% of
      hypertensives were controlled by WHO criteria and 24% by the NIH (p < 0.001).
      Frequency ratios for SBP, NIH criteria: W/B = 2.9, W/M = 2.6; WHO: W/B and B/M =
      1.7 and for DBP, NIH criteria: W/B = 1.6, W/M = 1.9 and WHO = W/B and W/M = 1.4.
      Main reason for compliance = Hy control; main reason for noncompliance forgetting
      the appointment date and/or disease in the appointment day. CONCLUSION:
      Compliance to appointment did not seem an advantage for treatment adherence and
      the results pointed out some characteristics of patients that need special
      attention to improve appointments and treatment compliance.

PMID- 9515253
TI  - [Abdominal aortic thrombosis mimicking aortic coarctation in a newborn with heart
      failure].
AB  - The case of a neonate in heart failure with the classical signs of coarctation of
      the aorta is described. Two dimension and Doppler echocardiography ruled out
      coarctation of the aorta and an abdominal ultrasonography detected a large
      thrombotic formation in the abdominal aorta, confirmed at necropsy.

PMID- 9515254
TI  - [Ventricular remodeling after acute myocardial infarction. Concepts,
      pathophysiology and therapeutic approach].

PMID- 9515255
TI  - [Mechanisms of acute ischemic syndromes and coronary atherosclerosis
      progression].

PMID- 9515256
TI  - [Influence of sex, age and coronary disease in the autonomic modulation of the
      heart].

PMID- 9515257
TI  - [HIV/tuberculosis co-infection: a request for a better surveillance].
AB  - The increasing endemicity of tuberculosis resulting from causes such as
      immigration, poverty, a declining public health infrastructure and co-infection
      by HIV/Mycobacterium tuberculosis, is leading to a change in tuberculosis control
      programmes. One of the main reasons for the resurgence of tuberculosis is HIV
      infection--the risk of tuberculosis is greater in HIV patients than in the
      majority of the population as can be seen from numerous research projects. The
      need for systematic testing for HIV infection in all tuberculosis patients by
      undertaking confidential HIV tests on admission to a tuberculosis programme is
      brought out. This measure would increase the number of cases diagnosed and
      provide data for better surveillance of the co-infection.

PMID- 9515258
TI  - Survey of cyclopids (Crustacea, Copepoda) in Brazil and preliminary screening of
      their potential as dengue vector predators.
AB  - INTRODUCTION: Cyclopid copepods are known to be good mosquito controllers,
      specially as regards the larvae of the dengue vectors Aedes aegypti and Ae.
      albopictus. MATERIAL AND METHOD: The objective of the study was to survey the
      local copepod fauna and search for new strains of M. longisetus var. longisetus,
      comparing the potential of the samples found with the current strain ML-01
      against Ae. albopictus larvae, under laboratory conditions. Eleven bodies of
      water in Campinas, SP, Brazil, were screened for copepods by collecting 1.5 l of
      water from each of then. The predatory potential of adults copepods was evaluated
      over 24 h, in the laboratory, for groups of 5 individuals preying upon 30 first
      instar Ae. albopictus larvae. RESULTS AND CONCLUSION: The following cyclopid
      species were found: Metacyclops mendocinus, Tropocyclops prasinus, Eucyclops sp,
      Eucyclops serrulatus, Eucyclops solitarius, Eucyclops ensifer, Macrocyclops
      albidus var. albidus and Mesocyclops longisetus var. longisetus. The predatory
      potential of these copepods ranged from nil to 97.3%. A sample collected in the
      field containing only M. longisetus var. longisetus showed the best control
      efficiency with no significant difference from a three-year old laboratory
      culture (ML-01) of the same species evaluated for comparison. The sample with few
      M. albidus var. albidus was ranked in second place showing an average 25.9%
      efficiency. The use of copepods in trap tires as dengue vector controllers is
      discussed.

PMID- 9515259
TI  - [Regular diet and cardiovascular disease risk factors].
AB  - INTRODUCTION: A survey by sampling in a county of the State of S. Paulo in 1990
      sought, by means of home interviews, to analyse the habitual diet and risk
      factors for cardiovascular disease of people over 20 years of age. METHODOLOGY:
      Of the sub-specimen of a comprehensive study population, 557 individuals, aged
      between 20 and 88, were interviewed. The habitual diet, characterized by the
      dietary history, was compared with the recommendations on energy and nutrients of
      the WHO and the risk factors (obesity, lipemic disorders and diabetes mellitus)
      diagnosed by the Body Mass Index and biochemical measurements. RESULTS AND
      CONCLUSIONS: It was observed that 60% of the population consume a diet with total
      energy below the estimated need and that the caloric contribution of
      carbohydrates was of 56%, of the lipids 29% and of the proteins 15%. However, by
      percentile analysis, the caloric contribution of lipids and of proteins was far
      above the recommended levels to the detriment of the carbohydrates. Energy,
      caloric distribution and quantity of cholesterol were satisfactory in only 5% of
      diets. Among the risk factors for the cardiovascular disease studied, obesity was
      found to be present in 38% of individuals, lipemic disorders in 26% and diabetes
      mellitus in 5%. Preponderantly light physical activity together with
      unsatisfactory diet, both in qualitative as in quantitative terms, aggravated
      this scenario still further.

PMID- 9515260
TI  - [Prevalence and risk factors of obesity in adults].
AB  - INTRODUCTION: A population-based cross-sectional study was conducted in Pelotas,
      Southern Brazil, with the objective of determining the prevalence of obesity and
      identify associated, variables as this condition increased markedly in the
      country between 1974 and 1989. MATERIAL AND METHODS: One thousand and thirty-five
      adults between 20 and 69 years of age were studied. Obesity was defined as a Body
      Mass Index--BMI--equal to or over 30 Kg/square meter). The multivariate analyses
      took into account the hierarchical model of the variables associated with obesity
      for both men and women. RESULTS: The prevalence for the overall population was of
      21% (CI 18-23). It was higher among women--25% (CI 22-29) than for men--15% (CI
      12-18). Socioeconomic status was positively associated with obesity among men,
      whereas the opposite situation was reported for women, with those belonging to
      the poorest social strata presenting increased BMI. Reported obesity in their
      parents was associated with increased BMI in the subjects, and this association
      remained statistically significant even after compensating for the effect of
      possible confounding variables. Self-reported diabetes and arterial hypertension
      doubled the risk of obesity, whereas non-smoking was associated with obesity only
      among women. Variables which were not associated with obesity after adjusting for
      confounders were alcohol consumption, marital status and parity. Women having
      more daily meals were less prone to obesity, even after controlling for
      confounders, and this association was not quite significant for men (p = 0.07).
      CONCLUSIONS: The prevalence of obesity was higher among women, and important
      differences in risk factors were noticed when the population was considered by
      sex.

PMID- 9515261
TI  - [Tobacco smoking among pregnant women in an urban area in southern Brazil, 1982
      93].
AB  - OBJECTIVE: A comparison between on the prevalence of smoking during pregnancy in
      1982 and that in 1993 in Pelotas, Southern Brazil. METHODOLOGY: Cross-sectional
      study. All hospital deliveries in 1982 and 1993--corresponding to over 99% of all
      births in those years--were studied. A total of 6,011 and 5,304 mothers were
      interviewed, respectively. RESULTS: The prevalence of smoking during pregnancy
      showed a small decrease from 35.7% in 1982 to 33.5% in 1993 (p < 0.05). In the
      two years under study, family income and number of antenatal care visits were
      inversely associated with the prevalence of maternal smoking. The rate of
      stopping smoking during pregnancy was 20.6%.

PMID- 9515262
TI  - [Epidemiological characterization of meningococcal disease in a metropolitan area
      in Southeastern Brazil, 1976-1994].
AB  - INTRODUCTION: Meningococcal disease continues to warrant assessment as to its
      endemic and epidemic multicausality and temporal trends in various locations.
      MATERIAL AND METHOD: Based on a standardization of epidemiological investigation
      of meningococcal disease in the municipality of Rio de Janeiro county,
      Southeastern Brazil, as from epidemic of the 1970s a study to characterized the
      epidemiological characteristics of the disease, was realized. The total of 4,155
      cases reported between 1976 and 1994 were analyzed in a retrospective,
      descriptive, and analytical study, using the epidemiological investigation forms
      issued by the Municipal Health Secretariat. Statistical analysis was performed
      using the chi 2, Wilcoxon-Mann-Whitney, and Kruskal-Wallis tests. RESULTS: The
      study resulted in the definition of three periods, classified as post-epidemic
      (1976-79), endemic (1980-86), and epidemic (1987-94), differentiated by the
      incidence rates and the predominant meningococcal serogroup. The mean incidence
      rates per period in the municipality were 3.51, 1.67, and 6.53 cases/ 100,000
      inhabitants, respectively. Serogroups A and C predominated during the post
      epidemic period, B and A in the endemic, and B in the epidemic. CONCLUSION: The
      mean case fatality rate remained virtually unchanged over time, but it varied by
      hospital, and during all three periods was lower in the State government
      reference hospital than in the other hospitals, whether public or private. The
      highest incidence and case fatality rates were associated with patients under one
      year of age, and the risk of acquiring the disease was greater among males. The
      highest incidence coefficients tended to occur in the same areas of the county
      during the three epidemiological periods, and the shanty-town population was at
      twice the risk of acquiring the disease.

PMID- 9515263
TI  - [Oral health status evaluation of pre-school children: longitudinal epidemiologic
      study (1993-1994), Cordoba, Argentina].
AB  - A one-year longitudinal survey was carried out on a sample of the Cordoba City 4
      year old kindergarten population (n = 820); so as to determine the role of
      several variables upon the incidence of caries. The dmf-t, dmf-s, oral hygiene
      and oral health indexes as well as incidence rates and caries relative risks of
      caries were inversely related to the socioeconomic level (SEL) of the children
      involved. Thus in the SEL III (typical proletariat, non-typical proletariat and
      sub-proletariat) children, the relative risk of caries was almost five times
      higher (RR = 4.9) than in the SEL I (entrepreneureal and managerial bourgeoisie)
      children. In SEL I, almost all new lesions occurred on smooth surfaces (61.2%),
      while in SEL III the molar occlusal faces were mainly affected (66.3%). Daily
      sugar intake was higher in SEL III children but experience of caries showed poor
      correlation to the amount (r = 0.40) and frequency (r = 0.52) of carbohydrate
      intake. No significant interlevel differences were observed in the biochemical
      salivary parameters analyzed. Assisted toothbrushing and fluoride topications
      strongly lowered the incidence of caries among SEL III children, also making the
      corresponding rates fall almost to SEL I values (0.31, 0.23 and 0.22 vs. 0.21).
      In conclusion, SEL III children should be treated prophylactically with effective
      preventive measures, because of their susceptibility to caries. Such preventive
      measures include assisted toothbrushing and fluoride topications.

PMID- 9515264
TI  - [Evaluation of the program for leprosy control in counties of the State of Mato
      Grosso, Brazil].
AB  - INTRODUCTION: A retrospective analysis of the Program for Leprosy Control in four
      counties of Mato Grosso State, on the Brazil-Bolivian frontier, has been
      undertaken in the present study. POPULATION AND METHODS: The health care service
      records of all patients registered by the Programs for Leprosy Control during the
      period from the beginning of their activities up to 1990 inclusive were checked.
      Final analysis was performed by epidemiological and operational indicators for
      the follow-up of control activities of Leprosy Control, as defined by the World
      Health Organization. RESULTS: An inadequate recording of information given by the
      patient was detected in more than half of all cases. The prevalence of leprosy
      varied from 15 to 48/10,000, in the period studied. The annual detection rate of
      new cases was 112/100,000 in 1990. CONCLUSION: The results suggest a high
      endemicity pattern for leprosy in the region. With regard to operational
      indicators our finding showed inadequate practice regarding all the activities of
      the program probably worsened by the poor qualification of the health workers
      involved in the assistance given.

PMID- 9515265
TI  - [Mental health care in health centers: study of the efficacy of the care given].
AB  - INTRODUCTION: The implementation of the mental health policy in the health
      centers of Campinas, Southeastern Brazil, is analysed. MATERIAL AND METHOD: The
      methodology used consisted of a descriptive epidemiological study of a sample of
      150 patients, discharged from a psychiatric hospital, and referred to health
      centers for continuing treatment. During the 4 months following discharge the
      attendance of the patients at these centers and return visits into hospital were
      verified. RESULTS: The results showed that 48.6% of the patients discharged by
      hospitals did not turn up at the health centers. Of those who did get those,
      51.4% abandoned their treatment before the end of the 4 months. The percentage of
      24.7% of the patients returned to hospital, most of them receiving a diagnosis of
      psychosis. CONCLUSIONS: The problems encountered in the implementation of the
      mental health policy in the health center network in Campinas as regards the
      definition of the policy, the organization of the work of the professional teams
      and the results these services achieve, were brought out. The evidence that the
      transformation of the asylum calls for new psycho-social rehabilitation services
      and intersectional articulation to obtain good results in de-hospitalization and
      the salvaging of the citizenship of mentally-ill patients is reinforced.

PMID- 9515266
TI  - [Microscopic analysis of "prato", "mussarela" and "mineiro" cheese sold in street
      markets of the City of Sao Paulo, southeastern Brazil].
AB  - INTRODUCTION: Cheese should be produced from ingredients of good quality and
      processed under hygienic conditions. Further, cheese should be transported,
      stored and sold in an appropriate manner in order to avoid, among other things,
      the incorporation of extraneous materials (filth) of biological origin or
      otherwise, in contravention of the relevant food legislation. The aim of the
      study was to evaluate the hygienic conditions of "prato", "mussarela", and
      "mineiro" cheeses sold at the street food markets in the city of S. Paulo,
      Brazil. MATERIALS AND METHOD: Forty-seven samples of each of the three types of
      cheese were collected during the period from March, 1993 to February, 1994. The
      Latin square was used as a statistical model for sampling and random selection of
      the street markets from which to collect the cheese samples. The samples were
      analysed for the presence of extraneous matters outside for which purpose the
      samples were washed and filtered and inside, for which the methodology of
      enzymathic digestion of the sample with pancreatine, followed by filtering, was
      used. RESULTS AND CONCLUSIONS: Of the 141 samples analysed, 75.9% exhibited at
      least one sort of extraneous matters. For the "prato" and "mussarela" cheeses,
      the high number of contaminated samples was due mainly to extraneous matters
      present inside the cheese, whereas in the "mineiro" cheese, besides the internal
      filth, 100% of the samples had external filth.

PMID- 9515267
TI  - [Human diphyllobothriasis in Patagonia, Argentina].
AB  - OBJECTIVE: In view of the amateur fishing practices and the importance of
      salmonids in the region the study sets out to detect human hosts in the Andean
      Patagonian zone. MATERIAL AND METHOD: Information campaigns were carried out by
      Clinical Analysis Laboratories of Andean Patagonia between 1986 and 1995 to
      detect diphyllobothriasis more efficiently by means of coproparasitological
      analysis. RESULTS: Further, forms were prepared for the collection of information
      about infection, treatment and the characteristics of the human host. During this
      period 13 new cases were registered either through direct identification of the
      parasite or through the presence of eggs in the faeces. The characteristics of
      infection are similar to those described for the genus Diphyllobothrium.
      CONCLUSIONS: The favourite game fish in Andean Patagonia are salmonids. This
      fish, often infected with plerocercoids, when eaten insufficiently cooked or cold
      smoked, constitutes the main source of human infection.

PMID- 9515268
TI  - [Evaluation of the dog population in an urban area of southeastern Brazil].
AB  - Planning control programs, for diseases such as rabies requires information on
      the size and structure of the dog and cat population. In order to evaluate the
      dog population of the urban area of Aracatuba city, S. Paulo State, Brazil, a
      survey was conducted using a questionnaire to interview members of house-holds.
      Eighty-eight districts were visited (37,778 houses) and the interview was
      possible at 77.93% of these. Human population size evaluated was 113,157
      inhabitants. Houses that owned animals represented 55.2%, 26,926 of the animals
      concerned were dogs and 5,755 were cats. Of the dogs, 56.64% were 1-4 year olds
      and males represented 56.2% of the total population. Dog: person ratio was
      estimated at 2.8 dogs to every 10 persons, almost 3 times the ratio hitherto
      estimated and used in the planning of rabies vaccination campaigns.

PMID- 9515269
TI  - [Occurrence of Achatina fulica Bowdich, 1822 (Mollusca, Gastropoda) in Brazil:
      intermediate snail host of angiostrongyliasis].
AB  - Achatina fulica, the intermediate snail host of angiostrongyliasis and also an
      agricultural pest, is being bred in Brazil for human consumption as "escargot".
      The snail has escaped from its artificial breeding sites and its dispersal in
      Itariri country, State of S. Paulo, is reported here for the first time. A.
      fulica is a transmitter of the rat lungworm Angiostrongylus cantonensis, nematode
      which causes meningoencephalic angiostrongyliasis; the risks of human
      contamination are commented on.

PMID- 9515270
TI  - [Motives for non-vaccination: critical review of the international literature,
      1950-1990].
AB  - Many countries have acknowledged that vaccination programs call for a mastery of
      technical and organizational elements if they are to become accessible to the
      population. One of these elements has been greatly underestimated: the
      participation of populations and their motivations. Experiences in several
      countries are here analysed, on the basis of a bibliographic revision of the
      period 1950-1990. Results show that existing studies vary in their conceptual and
      methodological focuses, according to the region in which research was carried out
      and to the kind of researcher involved. This fact is to be explained by the
      posture, common among researchers, of believing that they know in depth the
      subjective determinants of the behavior of the societies to which they belong.
      Based on this, they only use methodologies that allow them to arrive at a
      superficial understanding regarding the response of populations to the offer of
      vaccines.

PMID- 9515271
TI  - [Current challenges in medical education].

PMID- 9515274
TI  - [Private health system in Chile and the required physicians].

PMID- 9515273
TI  - [The Public Health Service in Chile and the required physicians].

PMID- 9515272
TI  - [Present and future of Chilean medical schools].

PMID- 9515275
TI  - [Changes needed at universities to modernize medical education in Chile].

PMID- 9515276
TI  - [Helping relationships and the training of future physicians].

PMID- 9515277
TI  - [Motivational and personality variables in medical school admission].

PMID- 9515278
TI  - [The admission process in Harvard Medical School].

PMID- 9515279
TI  - [Role of scientific research in the training of physicians].

PMID- 9515280
TI  - [Incentives for teaching activities through academic training].

PMID- 9515281
TI  - [Conclusions of the Chilean Association of Medical Schools seminar on medical
      education. Time for change in pre and post graduate medical education].

PMID- 9515282
TI  - [Effects of ramipril and spironolactone on ventricular remodeling after acute
      myocardial infarction: randomized and double-blind study].
AB  - BACKGROUND: Studies have shown that angiotensin converting enzyme (ACE)
      inhibition prevents left ventricular remodeling and cardiovascular events after
      an acute myocardial infarction. The role of aldosterone in ventricular remodeling
      after a myocardial infarction has not been addressed. AIM: To compare the effects
      of an ACE inhibitor, an aldosterone receptor antagonist and placebo on left
      ventricular remodeling after a first episode of transmural acute myocardial
      infarction. PATIENTS AND METHODS: Patients hospitalized for a first episode of
      acute myocardial infarction were blindly and randomly assigned to receive
      ramipril (2.5 mg bid), spironolactone (25 mg tid) or placebo. Ejection fraction,
      left ventricular end diastolic and end systolic volumes were measured by
      multigated radionuclide angiography, at baseline and after six months of
      treatment. RESULTS: Twenty four patients were assigned to placebo, 31 to ramipril
      and 23 to spironolactone. Age, gender, Killip class, treatment with
      thrombolytics, revascularization procedures and use of additional medications
      were similar in the three groups. After six months of treatment, ejection
      fraction increased from 34.5 +/- 2.3 to 40.2 +/- 2.4% in patients on ramipril,
      from 32.6 +/- 2.9 to 36.6 +/- 2.7% in patients on spironolactone, and decreased
      from 37 +/- 3 to 31 +/- 3% in patients on placebo (ANOVA between groups p <
      0.05). Basal end systolic volume was similar in all three groups, increased from
      43.4 +/- 3.4 to 61.4 +/- 6.0 ml/m2 in patients on placebo and did not change in
      patients on spironolactone or ramipril (ANOVA p < 0.05). End diastolic volume was
      also similar in the three groups, increased from 70.6 +/- 4.3 to 92.8 +/- 6.4
      ml/m2 in patients on placebo and did not change with the other treatments.
      CONCLUSIONS: Ramipril and spironolactone had similar effects on ventricular
      remodeling after acute myocardial infarction, suggesting that aldosterone
      contributes to this phenomenon and that inhibition of its receptor may be as
      effective as ACE inhibition in its prevention.

PMID- 9515283
TI  - [Intestinal permeability in alcoholic patients without liver damage].
AB  - BACKGROUND: Chronic alcoholism may increase intestinal permeability. However,
      there are few studies of intestinal permeability in chronic alcoholic subjects.
      AIM: To study intestinal permeability in chronic alcoholic patients without
      clinical evidences of liver damage, during early abstinence, and in normal
      subjects. METHODS: Thirty seven male subjects were studied, 18 controls and 19
      alcoholics. All subjects underwent an anthropometric assessment and dietary
      history. Lactulose/mannitol test was performed during the third day of abstinence
      in alcoholics. After an 8 hour overnight fast, subjects drank 200 ml of a
      solution containing 5 g lactulose and 5 g mannitol. Subsequently, urine was
      collected during the following 5 hours, where both sugars were measured by gas
      chromatography. RESULTS: Median values of lactulose/mannitol ratio were similar
      in alcoholics and controls (0.011, range 0.005-0.071 vs 0.014, range 0.005-0.027
      respectively). However, absolute urinary excretion of both lactulose and mannitol
      was lower in alcoholics. There was no relationship between nutritional status and
      urinary excretion of lactulose, mannitol or lactulose/mannitol ratio. CONCLUSION:
      In these alcoholic patients, no changes were observed in intestinal permeability.

PMID- 9515284
TI  - [Herpetic keratitis: clinical-virological correlation].
AB  - BACKGROUND: Herpetic keratitis is the main infectious cause of corneal opacity.
      The existence of effective antiviral agents underscores the need of an early
      diagnosis. AIM: To correlate clinical features of herpetic keratitis with
      virological studies. PATIENTS AND METHODS: Forty one patients with a clinical
      diagnosis of herpetic keratitis were studied. Viral isolation, polymerase chain
      reaction (PCR) and typification were done in a sample taken by swabbing the
      ocular lesion. RESULTS: Twenty six patients (31% female) had epithelial
      keratitis, that was mild or moderate in 88% of cases and acute in 77% of them. In
      20 patients (77%), viral isolation and PCR were positive (HSV-2 in one case).
      Fifteen patients (67% female) had stromal keratitis, 93% of cases were moderate
      or severe and 53% were acute. Viral isolation was negative in all cases and in
      20% PCR was positive. CONCLUSIONS: Viral isolation and PCR were equally sensitive
      in epithelial keratitis, but in stromal keratitis only PCR could detect the
      virus. Moderate acute dendrite was the predominant clinical manifestation. The
      higher proportion of women with stromal keratitis supports its possibly
      autoimmune etiology. HSV-2 is seldomly isolated and possibly associated to
      vertical transmission.

PMID- 9515285
TI  - [Immune response reduced by intense intellectual stress: changes in lymphocyte
      proliferation in medical students].
AB  - BACKGROUND: There is a relationship between stressful situations and the
      susceptibility towards certain diseases, probably mediated by immune system
      modifications. AIM: To study T lymphocyte proliferation in medical students
      during periods of differing academic stress. SUBJECTS AND METHODS: Blood samples
      were obtained from 42 medical students during a period of moderate academic
      stress, immediately before a final examination and after their summer vacations.
      T lymphocyte proliferation in response to 5, 10 and 20 mg/ml phytohemagglutinin
      was measured by the incorporation of 3H-thymidine, and plasma cortisol was
      measured by RIA. RESULTS: T lymphocyte stimulation index in response to all
      phytohemagglutinin concentrations was significatively lower in the period before
      examination than in the other two periods. There were no differences in the index
      between the period of moderate stress and after summer vacations. Plasma cortisol
      levels were 15.6 +/- 4.3, 18.6 +/- 5.8 and 16.7 +/- 5.1 mg/dl during the periods
      of moderate stress, before the examination and after vacations, respectively (p <
      0.05 for the difference between examination and the other two periods).
      CONCLUSIONS: There is a decrease in lymphocyte proliferation and an increase in
      cortisol levels during a period of acute academic stress in medical students,
      suggesting that, the exposure of the healthy subjects to common stressful
      stimuli, may affect their immunocompetance.

PMID- 9515286
TI  - [Gastroesophageal reflux and obesity].
AB  - BACKGROUND: There is a possible relationship between gastroesophageal reflux and
      overweight, that has not been studied extensively. AIM: To study the association
      between overweight and gastroesophageal reflux in a group of patients and normal
      controls. SUBJECTS AND METHODS: Body mass index of 85 patients with
      gastroesophageal reflux and 100 patients with Barrett esophagus, was compared
      with that of 171 healthy controls. RESULTS: There were no differences in body
      mass index between healthy subjects and patients with gastroesophageal reflux.
      However, there was a higher proportion of overweight males and obese females with
      Barrett esophagus than among healthy controls. CONCLUSIONS: We did not find an
      association between overweight and gastroesophageal reflux, but patients with
      Barrett esophagus had a higher body mass index than normal controls.

PMID- 9515287
TI  - [Non operative treatment of liver and spleen trauma. Clinical experience].
AB  - BACKGROUND: There is a tendency towards conservative behaviours in the treatment
      of blunt abdominal trauma. AIM: To perform a retrospective analysis of the
      results of conservative management of liver and spleen trauma. PATIENTS AND
      METHODS: Clinical charts of 21 patients with traumatic lesions of liver or spleen
      that were not operated, seen between 1991 and 1996, were reviewed. Severity of
      trauma was assessed according to the Abbreviated injury scale of 1985 and CAT
      scan lesions were scored according to scale proposed by the American Association
      of Trauma Surgery. RESULTS: Mean age of patients was 33.4 years old and 17 were
      male. Twelve patients had liver trauma, that had a mean severity index of 20.1.
      According to abdominal CAT scan, two patients had grade II lesions, 8 had grade
      III lesions and 2 had grade IV lesions. Two patients required transfusions and
      all had a successful recovery. Nine patients had spleen trauma, with a severity
      score of 24.4. Three patients required transfusions and one was subjected to a
      splenectomy. Mean hospital stay was 17.8 days for patients with liver trauma and
      16 days for patients with spleen trauma. CONCLUSIONS: Non operative management of
      liver and spleen trauma is feasible and safe in a selected group of patients,
      independent of the degree of injury and hemoperitoneum.

PMID- 9515288
TI  - [Autoimmune hepatitis in a girl with presence of anti-LKM1 antibodies].
AB  - Autoimmune hepatitis is an inflammatory liver disease characterized by dense
      mononuclear cell infiltrate in the portal tract, and serologically by the
      presence of non-organ and liver-specific autoantibodies and increased levels of
      gammaglobulins in the absence of a known etiology. Three subgroups of autoimmune
      hepatitis have been recognized, depending on the nature of the autoantibody
      present in the serum: Type 1 autoimmune hepatitis, associated with smooth-muscle
      (SMA) or antinuclear antibody (ANA) seropositivity; type 2, with anti
      liver/kidney microsome antibody (anti-LKM1), and type 3, with the absence of ANA,
      SMA and anti-LKM1 and presence of other autoantibodies such as anti-soluble liver
      antigen (SLA). Subtypes of chronic autoimmune hepatitis have clinically different
      features and prognoses. An 8 year old female patient presented mild jaundice of
      insidious onset. The liver was tender and enlarged. Serologic markers for A, B,
      C, E, Epstein Barr and cytomegalovirus were negative. The liver biopsy showed a
      histological picture consistent with chronic active hepatitis. High titers of
      anti-liver/kidney-microsome antibody were found by indirect immunofluorescence
      test, and this finding was confirmed by Western blot against specific liver
      microsome antigens. Therapy with prednisolone induced a clinical and biochemical
      remission after four weeks. The suspension of therapy under strict medical
      control produced a rapid relapse of clinical and biochemical features. The
      reinitiation of prednisolone was successful, and an alternate-day program was
      started and maintained until 8 months follow-up.

PMID- 9515289
TI  - [Evaluation of treatment with cyclosporine in three patients with pulmonary
      fibrosis].
AB  - There are few reports on the use of cyclosporine in idiopathic pulmonary
      fibrosis, in experimental animals or humans. We report three patients with
      advanced pulmonary fibrosis in whom steroid therapy failed and that received
      cyclosporine in a dose of 3 to 5 mg/kg for three to five months. One patient
      developed systemic hypertension that subsided reducing the dose of cyclosporine.
      No positive changes in dyspnea were obtained and pulmonary function tests
      deteriorated during the treatment period. We conclude that cyclosporine treatment
      had no clinical benefit in these patients with pulmonary fibrosis.

PMID- 9515290
TI  - [Mycotic aneurysms and multiple peripheral embolisms in a patient with infectious
      endocarditis].
AB  - Sepsis from an infected cardiac valve can lead to bacterial seeding and
      destruction of the arterial wall with formation of a mycotic aneurysm. The
      natural history of these lesions is the rupture. We report the case of a 20 year
      old female who was admitted to our institution with massive mitral regurgitation
      and emboli of the central nervous system and both lower extremities. She
      underwent emergency valve replacement and then, staged treatment of her ischemic
      legs and multiple asymptomatic mycotic aneurysms: Superior mesenteric, right
      common iliac and left superficial femoral arteries. A splenectomy was required to
      treat a splenic abscess. An aneurysm of a peripheral branch of the middle
      cerebral artery was medically treated, demonstrating reduction in size on
      subsequent angiogram. She recovered uneventfully and remains asymptomatic after
      20 months of follow up. The development of new diagnostic and therapeutic tools
      has led to a decrease of these complications during infectious endocarditis.
      However, in the patient with late diagnosis and symptoms in different
      territories, the mycotic aneurysm must be kept in mind to provide the patient
      with appropriate treatment.

PMID- 9515291
TI  - [Scientific ethics of the origin of humans].
AB  - The analysis of the early human life from the view point of a scientific ethics
      is presented. Life is a historical materioenergetic process of specific
      organization. This phylo-ontogenetic process is a continuous process without
      interruption. Biology has demonstrated that human eggs or embryos are full human
      individuals, even though not all human conception is a human being. The
      contradictions involved in taking ethical decisions after knowing the percentage
      of conceptions obtained by in vitro or in fallopian tube fertilization that reach
      the birth are shown. The advantages of scientific ethics in the analysis of the
      origin of the different positions are indicated. These advantages come from the
      dissection of the different cognitive, affective-emotional and value attribution
      frames involved in the alternative decisions.

PMID- 9515292
TI  - [Medicine at the crossroads].
AB  - This article is based in the book by Dr M Konner "Medicine at the crossroads".
      Medicine must be analyzed in three levels: the structure of the global society
      and its relationship to the population's health; the institutions dedicated to
      health protection and promotion; and health related professions. The commented
      book is specifically focused on medical profession. The main problems of the
      profession and its role in society are analyzed. The excessively hierarchical and
      technological, and thus dehumanized, relationship between physicians and
      patients. The high volume of surgical procedures and the exaggerated dependence
      on medications. The lack of preoccupation for mental disorders, the artificial
      prolongation of life and several other problems. The problems that arise when
      medical profession is inserted in market economy are analyzed, based on Chilean
      experience. That debilitates its trusteeship virtue, that is the basis of its
      social and political status. The contradictions that are generated by this new
      tendency of the profession and the strategies to face them are depicted.

PMID- 9515293
TI  - [Do androgens modulate luteinizing hormone secretion in women?].
AB  - In hyperandrogenic states an abnormal pattern of LH secretion in women is
      observed, which is presumed to result from a direct action of androgen or its
      conversion to estrogen. Two strategies are available to study the effect of
      testosterone on LH secretion. One involves the use of non-steroidal compounds
      that block the negative feedback actions of endogenous androgens by binding to
      androgen receptors; the other consists only in the administration of androgens.
      Following these two strategies, we first studied the pulsatile gonadotrophin
      secretion in hyperandrogenic women, following flutamide administration, a
      specific androgen receptor blocker. Flutamide treatment was followed by a
      decrease in LH pulse amplitude and mean LH concentrations, demonstrating that
      androgen receptor blockade reduces LH secretion in hyperandrogenic women. To
      establish the level at which the androgen effect is exerted, we further studied
      the acute effect of testosterone (hyperandrogenic levels) and the blockade of its
      receptor on LH secretion in patients with severe hypothalamic deficiency treated
      with pulsatile GnRH (GnRHp). LH pulse profiles were assessed under GnRHp
      treatment alone, during testosterone and during testosterone and flutamide
      administration. Testosterone increased LH secretion and LH pulse amplitude.
      Flutamide significantly reverted the LH increase induced by testosterone. These
      results strongly suggest that testosterone in the hyperandrogenic female range,
      may facilitate LH secretion by the pituitary, effect that is reversed by the
      blockade of the androgen receptor.

PMID- 9515294
TI  - [Posthumous nomination for Medicine Nobel Prizes II. The positivism era (1849
      1899)].
AB  - The author proposes the nomination of great physicians of the second half of the
      XIX century for a posthumous Medicine Nobel Prize. The valorization given by
      medical historians Garrison, Lavastine, Castiglioni, Lain Entralgo and Guerra, is
      used to select the better candidates. One to three names are assigned by year
      from 1849 to 1899. Four categories of Nobel prizes are assigned: a) Basic
      biological disciplines, b) Clinical and surgical medicine, pathology and
      specialties, c) Discoverers of transcendental diseases that are eponyms and d)
      New medical technologies. A total of 84 nominees for the Nobel Prize are
      presented. These lists are presented as preliminary and tentative to allow an
      extensive debate about the history of medicine during the nineteenth century.

PMID- 9515296
TI  - [Ethical contribution from Dolly].

PMID- 9515295
TI  - [The disease of admiral Christopher Columbus].
AB  - Based on diaries and relations, the fact that Admiral Cristobal Colon effectively
      suffered of gout is documented. This was a common disease in that times. The
      interpretations that gout as a disease has had in the course of medicine history,
      are also analyzed.

PMID- 9515297
TI  - [The development of epidemiologic research in psychiatry].
AB  - The article reviews the history of psychiatric epidemiology: five generations of
      American studies and future directions are described. There is also information
      on European studies and a brief history of classifications of mental disorders.

PMID- 9515298
TI  - [Prime-MD as a method for the diagnosis of mental disorders in primary health
      care].
AB  - A random sample of 150 people has been assessed. Prime-MD appears to be a useful
      tool for rapid diagnosing of mental disorders in primary care health and
      epidemiological research.

PMID- 9515299
TI  - [Suicide attempts in epileptic patients during the years 1990-92. Analysis of
      patients in the Regional Poison Control Center in Sosnowiec].
AB  - During the years 1990-92 in the Regional Poisons Control Center in Sosnowiec 42
      epileptics (20 females and 22 males) were hospitalized because of suicide
      attempt. It amounted to 9% of all attempters, treated there in this period. The
      majority of patients were males of age range from 21 to 62 years. In 23 patients
      the suicide attempts were performed for the first time. the main reason for
      suicide was the family conflicted situation. Additionally, in 14 patients the
      poisoning attempts have been done during alcohol abuse. In the suicide attempts
      the antiepileptic drugs were most frequently used, mainly carbamazepine (23
      cases).

PMID- 9515300
TI  - [Depression in children: prospective studies].
AB  - Prospective longitudinal observation of children socially and emotionally
      immature and depressive at entering school was carried on till their early
      adolescence. The study's aim was to describe: 1. childhood depression dynamics,
      2. developmental changes in depression, 3. factors related to the depression
      course, 4. relation of childhood depression to adolescence depression. A
      screening study of representative population of school entering children led to
      identification of a risk group followed-up 3 and 6 years later. The Krakow
      Depression Inventory (AO "B1" and IO "B1") was used to diagnose, and for analysis
      of depression. Results of the study revealed a tendency to chronic course of
      depression in the studied group. Data collected at the first and the second stage
      showed coincidence of the depression chronicity and a set of nonspecific factors
      of "biological vulnerability" on the one hand, and dysfunctional family on the
      other. The latter was characterized by unclear family boundaries and difficult
      relational individuation. Data collected at the third stage of the study showed
      persistence of depression in the same individuals. Entering adolescence seemed to
      have no impact on depression prevalence in the studied group. It was, however,
      evident that cognitive and general activity disturbances increased among those
      studied who were not diagnosed depressive in the second and third stage. This
      finding requires further studies.

PMID- 9515301
TI  - [The use of the restraint in Warsaw psychiatric hospitals before and after the
      introduction of the Mental Health Act].
AB  - The goal of the research was evaluation how, and to what degree the use of
      restraint in psychiatric hospitals was changed between 1989 and 1996. Two month
      observations of the 11 psychiatric wards of Warsaw psychiatric hospitals were
      conducted. Researchers used special questionnaire to account for all of the cases
      of restraint. The first research of this sort was performed in 1989, the second-
      in 1996. Each of the observed wards was described in terms of its conditions,
      equipment, personnel, the local customs and population of patients (T. Stanczak's
      questionnaire was used here); global level of pathology was described with the
      shortened version of Kellam's form. The most important difference between the
      characteristics of using restraint in 1996 and 1989 is the average time of
      remaining in restraint: it became distinctly shorter. The percentage of restraint
      grew after the act was issued but less patients were restrained. More often than
      in 1989 aggressive behaviour was the reason for restraining patients. The
      research clearly states that the practice of restraint was evidently modified and
      the freedom of its use limited. The main causes are probably the introduction of
      the Mental Health Act and the changes in the observed wards.

PMID- 9515302
TI  - [Forensic detention as a preventive measure on the basis of the analysis of
      documentation of patients at the Ciborz Psychiatric Hospital during 1958-1993].
AB  - The aim of this work was efficiency estimation of forensic detention, according
      to kinds of psychiatric disorders. The research included also the form and
      intensity of treatment. The study was made in Ciborz Mental Hospital and covered
      262 internee patients during 35 years. The argument that efficiency in the
      psychotic group was higher was not confirmed. The correlation between complexity
      and efficiency was not found. The dependence between non-biological treatment and
      efficiency of detention was confirmed.

PMID- 9515303
TI  - [Life threatening metabolic and pathophysiological complication in anorexia
      nervosa patients].
AB  - Medical records of 210 adolescents hospitalised because of anorexia nervosa (1978
      1995) were analysed. 8 patients have demonstrated life threatening metabolic and
      pathophysiologic complications. These complications were seen in cachectic
      patients or when their body mass index decreased in a very short time. They were
      parenterally fed. When physical state permitted, family and individual
      psychotherapy was introduced.

PMID- 9515304
TI  - [Opinions regarding the importance of body image disorders in the development and
      in the course of eating disorders].
AB  - The article presents a review of most important research results as well as
      opinions about the role and importance of body image disturbances in the
      development and the course of eating disorders. It also contains a review of
      definitions of body image, and techniques used in the evaluation of this type of
      disorders.

PMID- 9515305
TI  - [Psychotherapy and pharmacotherapy: alternative or complimentary methods of
      treatment?].
AB  - Controversial arguments of proponents and opponents of combining psychotherapy
      and pharmacotherapy are discussed. The authors argue that in some circumstances
      the combined treatment is optimal. However, its application requires high skills
      and knowledge of the therapists.

PMID- 9515306
TI  - [The influence of alprazolam on the symptoms of anxiety and depression].
AB  - The work describes the analysis of influence of alprazolam on anxiety psychic and
      somatic symptoms. Subscales were distinguished using the factorial analysis
      method.

PMID- 9515308
TI  - Health needs of women with mental retardation and developmental disabilities.

PMID- 9515307
TI  - [The use of chlorazepate dipotassium (Tranxene) in the states of restlessness and
      agitation].
AB  - Clorazepate dipotassium (Tranxene), benzodiazepine of retarded anxiety-relieving,
      sedative and sleep-inducing action was used in an open sample of 36 patients for
      fast control of anxiety and aggression in the course of schizophrenia,
      schizoaffective psychosis and other psychotic disorders. The intensity of
      aggressive behaviors was assessed as 6-7 items on the CGI scale. After
      intramuscular injection of clorazepate complementing the so-called basic
      treatment in the mean daily dose of 150 mg, several hours lasting sedative effect
      was achieved. No unfavourable interactions between the applied clorazepate
      (Tranxene) and the other medicines applied simultaneously (mostly neuroleptics
      and antidepressant drugs) were observed. Clorazepate (Tranxene) is an effective
      and safe drug giving fast and long-lasting sedation of the patients with low risk
      of interaction with other drugs or of side-effects.

PMID- 9515309
TI  - How to hire the best employee.

PMID- 9515310
TI  - Internal marketing: the five R's.

PMID- 9515311
TI  - One practice's intraoral camera success story.

PMID- 9515312
TI  - More staff, higher salaries sum up staffing patterns.

PMID- 9515313
TI  - Breaking out of debtor's prison.

PMID- 9515314
TI  - A well-planned expansion.

PMID- 9515315
TI  - The wonderful world of independent contractors.

PMID- 9515316
TI  - Regulatory and business issues relating to leasing.

PMID- 9515317
TI  - Maybe you should buy an intraoral camera.

PMID- 9515318
TI  - Maximizing your investment in an intraoral camera.

PMID- 9515319
TI  - Sports dentistry--the rewards of community service.

PMID- 9515320
TI  - Minimal invasive dentistry: a revolution long overdue.
AB  - My standard admonition still pertains: scale all surfaces, supragingival and
      subgingival, after any type of cementation. You will be embarrassed by the amount
      of residual cement left after removal with an explorer.

PMID- 9515321
TI  - A simple way to educate your patients about their benefits.

PMID- 9515322
TI  - Practice success.

PMID- 9515323
TI  - The management Rx.

PMID- 9515324
TI  - In-your-face interface is the hub.

PMID- 9515325
TI  - An educated vision about software.

PMID- 9515326
TI  - Where do imaging systems fit?

PMID- 9515327
TI  - Exploring new practice dimensions: space shuttle not required!

PMID- 9515328
TI  - Add patient education to other uses for CD-ROMs!

PMID- 9515330
TI  - Charting for the jury.

PMID- 9515329
TI  - Do you gaze upwards after sinning?

PMID- 9515332
TI  - Payment solutions.

PMID- 9515331
TI  - This sales pitch doesn't match the tacky shoes.

PMID- 9515333
TI  - Practice transitions.

PMID- 9515334
TI  - Knowledge-based systems, removable partial denture design and the development of
      RaPiD.
AB  - Knowledge-based systems (KBS), otherwise and formerly known as 'expert systems',
      are computer programs that contain a representation of knowledge that can be used
      to solve problems normally requiring human intelligence. This article discusses
      the contributions such systems can make to medicine and dentistry, indicates the
      range of existing dental KBSs and gives reasons why removable partial denture
      (RPD) design has attracted so much attention in this respect. A description is
      also given of the 'RaPiD' system for designing RPDs at the chairside.

PMID- 9515335
TI  - Ectodermal dysplasia in adulthood: the restorative difficulties and management.
AB  - Ectodermal dysplasia can result in a number of oral problems. As the condition is
      usually diagnosed in childhood, multidisciplinary specialist dental care at an
      early age may minimize the long-term dental complications. This article describes
      the restorative management of an adult patient suffering from ectodermal
      dysplasia for whom such support was not available, resulting in the provision of
      complex and highly invasive restorative treatment in adult life to provide a
      functional and aesthetically acceptable dentition. The various treatment options
      that were considered are discussed together with the details of the treatment
      provided.

PMID- 9515336
TI  - The challenge of preparing the curved root canal.
AB  - Heavily restored teeth which become pulpally involved are now often root canal
      treated rather than extracted. While this is laudable it has a significant impact
      on the practice of endodontics today. The curved calcified canal can prove very
      difficult to prepare to its natural shape by conventional techniques and there is
      always the likelihood of iatrogenic damage. To compensate for this many
      clinicians tend to under-prepare these canals, perhaps leaving them inadequately
      cleaned and certainly remarkably difficult to fill to length. The purpose of this
      article is to outline the stages of and the rationale behind a hand
      instrumentation preparation method which uses the balanced force method of
      movement of files from canal entrance to apical constriction. In the authors'
      experience this technique has gone a long way towards solving the problem of
      cleaning and shaping the fine curved canal. With some practice, but no extra
      expense, the technique described will not only speed up canal preparation but
      will also make it more predictable.

PMID- 9515337
TI  - Trouble-free dental local anaesthesia.
AB  - Although administration of local anaesthesia in dentistry is generally both safe
      and effective, problems do occur. This article summarizes the types of problem
      the dental practitioner may encounter, in the hope that increased awareness will
      decrease the incidence.

PMID- 9515338
TI  - Treatment planning for dental implants: considerations, indications, and
      contraindications.
AB  - During the last 10 years the initial concept of osseointegrated implant dentistry
      as essentially treatment of the heavily resorbed edentulous mandible in older
      patients has expanded to encompass almost every combination of prosthetic
      problem. Many factors must be taken into account when planning treatment to
      ensure a flexible approach which is necessary given the uncertainty in predicting
      the outcome of difficult cases. The complex, and therefore inherently costly,
      nature of implant dentistry will inevitably lead the patient to have very high
      expectations of treatment. It is extremely important for the operator to
      determine these expectations at an early stage, and if there is any doubt about
      being able to satisfy them then he or she may be wiser not to proceed (as in all
      other areas of dentistry, skillful case selection is the key to success). In any
      event, the patient must be fully appraised of the complications, the potential
      risks and the benefits of treatment so that they can proceed on the basis of
      informed consent.

PMID- 9515339
TI  - Dental therapists: their future role in the dental team.

PMID- 9515340
TI  - Antibiotic prophylaxis in dental surgery.
AB  - Prevention of infection can be a minefield of uncertainty. There is little
      consensus of opinion on the objective criteria for diagnosing wound infection,
      and experts disagree on whether antibiotics should be routinely provided as
      prophylaxis in dental surgery. This article sets out the arguments for and
      against the prophylactic use of antibiotics in dental procedures.

PMID- 9515341
TI  - Problems complicating dental treatment with local anaesthesia or sedation:
      prevention and management.
AB  - The provision of dental treatment under both local anaesthesia and sedation has
      an excellent safety record. However, problems that either complicate treatment or
      lead to medical emergencies can arise. This paper considers the prevention of
      foreseeable problems and the treatment of unforeseeable emergencies in the dental
      surgery.

PMID- 9515342
TI  - Entrapped lip following sport injury.
AB  - A case is presented of a patient whose lip became entrapped onto his orthodontic
      bracket following a blow to his face during a contact sport. The entrapped mucosa
      had to be released surgically.

PMID- 9515343
TI  - Implant placement: surgical techniques and considerations.
AB  - Successful implant surgery largely depends on good planning and meticulous
      technique. The former requires an appreciation of the restorative requirements
      and visualization of the desired end result. This may be easier for the clinician
      who is delivering both aspects of treatment, but in other circumstances requires
      close collaboration between prosthodontist and surgeon. This paper focuses on the
      surgical techniques involved in implant surgery, because successful
      osseointegration is achievable only with careful surgical preparation.

PMID- 9515344
TI  - A caries control programme for adult patients.
AB  - This paper concerns the management of an adult patient with a caries problem.
      Once a dentist has decided the patient is at high risk to dental decay,
      involvement of the patient in the management of the problem is essential because
      it is the patient who will control caries, not the dentist. It is essential to
      determine why the patient is at risk so that risk factors may be modified
      appropriately. All members of the dental team have a role to play.

PMID- 9515345
TI  - Marks out of ten?

PMID- 9515346
TI  - Thermoplasticized gutta percha obturation techniques.
AB  - Gutta percha is the most widely used material in root canal obturation because of
      its relative inertness, lack of toxicity and biocompatibility. The most common
      method of obturation using gutta percha is lateral condensation, which has
      several disadvantages. The use of thermoplasticized gutta percha obviates many of
      the problems of this technique, but is still not commonly used. This article
      assesses the systems available for obturating root canals using thermoplasticized
      gutta percha.

PMID- 9515347
TI  - Making the best use of consultant orthodontic services. Part 1: Determining which
      patients require referral.
AB  - General dental practitioners and community dental officers may need to consider
      several factors when referring patients to the consultant orthodontic service. In
      Birmingham, a local professional group incorporating representatives from both
      primary care and secondary care (consultant) services have drawn up a set of
      formal referral guidelines. The purpose of the exercise was to encourage the most
      appropriate use of the consultant service so that its resources could be directed
      towards those in greatest need. In this paper, the factors which determine the
      patients requiring referral are discussed; a second article will deal with the
      actual process of referral.

PMID- 9515348
TI  - A retrospective survey of patients treated with one-stage (ITI) endosseous
      implants.
AB  - Reports of the success of treatment using endosseous implants vary, and claims
      about the usefulness of some implant systems are supported by little hard data.
      The authors of this report followed the progress of patients who had been
      implanted with the ITI Bonefit implant system over a period of 5 years. They
      present the results of their study and give recommendations on how general dental
      practitioners (GDPs) should be trained to use such implants.

PMID- 9515349
TI  - The restoration of posterior teeth with composite Resin. 2: Indirect-placement
      composite.
AB  - The first article of this series described the problems of restoring posterior
      teeth with direct-placement composite. This second article discusses the
      advantages and disadvantages of the composite inlay technique and examines the
      clinical provision of these restorations.

PMID- 9515351
TI  - Practice-based research?

PMID- 9515350
TI  - Sedation in dental practice. 3: The role of sedation in the management of
      problems with local anaesthesia.
AB  - This article describes how sedation can help to overcome some of the problems
      associated with the use of local anaesthesia for dentistry. It also reviews those
      problems where sedation is not the appropriate choice, and gives guidance on
      distinguishing the appropriate from the inappropriate, along with suggestions for
      how such cases might be managed.

PMID- 9515352
TI  - Reconstruction techniques in oral carcinoma.
AB  - Resection of oral carcinoma can cause serious problems with speech, mastication
      and swallowing. Several methods of reconstruction of the defects caused by tumour
      resection are available to the modern oral and maxillofacial/head and neck
      surgeon, some of which are more effective and aesthetically pleasing than others.
      This article discusses the methods available, their advantages and disadvantages,
      and gives guidelines on the circumstances in which each is ideally used.

PMID- 9515354
TI  - The triangle of health. 1: The clinical arena.
AB  - The triangle of health is based upon a holistic view of health and is composed of
      physical, psychological and social dimensions. It is by an acknowledgement of
      these various aspects of health that restorative treatment and preventive plans
      can best be negotiated with patients and tailored to their physical,
      psychological and social needs.

PMID- 9515353
TI  - Sedation in practice. 4: The use of sedation for the medically compromised
      patient.
AB  - This, the fourth paper in a series of uses of sedation in general dental
      practice, reviews the use of sedative techniques for patients who have medical
      conditions which will affect their ability to co-operate with dental treatment or
      which may be aggravated by the stress of treatment. Advice is given on a range of
      other conditions which may present as incidental findings when the patient's
      medical history is being taken.

PMID- 9515355
TI  - Oral manifestations of leukaemia.
AB  - Patients with leukaemia can exhibit signs or complain of symptoms in the oral
      cavity and oropharynx; indeed, these may be the initial presenting complaints of
      the disease. Septicaemia is common in patients undergoing treatment, and has been
      reported as having an oral cause in up to 50% of cases. This article reports four
      patients presenting to dental practitioners with leukaemia, and discusses the
      management of dental problems in patients with the disease.

PMID- 9515356
TI  - Treatment of localized anterior toothwear with composite restorations at an
      increased occlusal vertical dimension.
AB  - Patients may present with localized anterior toothwear, complaining of poor
      appearance or sensitivity, or both. Restoration of these teeth continues to cause
      problems, especially if interocclusal space has been lost. Conventional treatment
      to satisfy the patient's aesthetic and functional demands is time consuming and
      requires careful maintenance. This paper describes the use of chairside composite
      resin restorations in the treatment of localized anterior toothwear. Interoccusal
      space is provided by placing the restorations at an increased vertical dimension
      of occlusion. It enables the presenting complaint to be resolved while restoring
      structure, function and appearance.

PMID- 9515357
TI  - Making the best use of consultant orthodontic services, Part 2: How to undertake
      the referral.
AB  - The previous article in this series dealt with the selection of patients who
      would benefit from referral to a consultant orthodontist. It is equally important
      to access consultant services in a manner which allows the referral to be
      processed efficiently. This paper discusses factors related to the actual
      mechanism of referral.

PMID- 9515358
TI  - How wet is wet?

PMID- 9515359
TI  - In defence of transplants: a case report.
AB  - This article reviews the transplantation of maxillary canines: indications,
      contraindications, surgical technique, and success rates. A successful case is
      illustrated.

PMID- 9515360
TI  - The traumatic anterior overbite.
AB  - The position of the anterior teeth and skeletal base relationship establish many
      of our facial characteristics, yet these same tooth positions can result in a
      range of dental problems that are often specific for a particular incisal
      relationship. Excessive loss of tooth tissue on various surfaces may result in
      trauma to the soft tissue and temporomandibular joint dysfunction. A range of
      treatment options may be required and can often be conveniently classified by the
      form of incisal relationship.

PMID- 9515361
TI  - Dentist and patient evaluation of an electronic dental analgesia system for
      controlling discomfort of injections.
AB  - A number of dedicated electronic dental analgesia (EDA) systems have become
      available in recent years. In this study the attitudes of operators and patients
      were investigated by means of a post-treatment questionnaire, to the use of a new
      system for providing surface anaesthesia before administration of local
      anaesthesia. Levels of effectiveness were rated as similar to those of surface
      anaesthesia by the dental evaluators, who found the EDA system more time
      consuming. They felt that the EDA system reduced the discomfort of injections in
      only 26% of cases. Sixty per cent of the respondent patients who had previously
      experienced surface anaesthesia thought the EDA system controlled injection
      discomfort, and 64% stated that they would request the system in future.

PMID- 9515362
TI  - The role of implants in restorative dentistry. 1: The replacement of missing
      teeth.
AB  - Missing teeth, whether, congenitally absent or lost through trauma or caries may
      lead to reduced friction, poor aesthetics or distress to the patient. A variety
      of methods have therefore been developed to replace the missing dentition with
      bridgework or dentures. The method chosen for replacement should be tailored
      towards the individual patient as far as possible. In this article, the first in
      a series, the author provides guidelines as to how this should be done.

PMID- 9515363
TI  - Endodontic radiography.
AB  - The ability to take radiographs of good diagnostic quality is an essential
      prerequisite for successful root canal therapy. However, the operator also has a
      responsibility to limit the radiation dose to the patient. This article reviews
      the radiography required for root canal treatment with these criteria in mind.

PMID- 9515364
TI  - Emergency treatment of acute temporomandibular disorders: Part 1.
AB  - The purpose of this short series of articles is to provide guidance in the
      management of patients who present with an acute temporomandibular disorder. This
      article is the first of two, highlighting the role of the general dental
      practitioner in the primary care of acute temporomandibular disorders.

PMID- 9515365
TI  - A dental Wish List?

PMID- 9515366
TI  - Occlusal 'hidden caries'.
AB  - The term 'hidden caries' is used to describe a carious lesion seen in dentine on
      a bitewing radiograph where clinically the occlusal enamel appears sound or only
      minimally demineralized. The relative rise in the number of clinically sound
      occlusal surfaces over the past two decades could be a reason why hidden caries
      has come into sharper focus for practitioners and researchers. Dentists,
      routinely examining children who are clinically caries-free, may be shocked to
      discover a large lesion on a radiograph that they have apparently missed
      clinically. This underlines the importance of careful examination of the
      radiograph. It is important that the practitioner appreciates the possibility of
      hidden caries, and the value of the radiograph in its diagnosis.

PMID- 9515367
TI  - Emergency treatment of acute temporomandibular disorders: Part II.
AB  - In this, the second part of a presentation on the emergency treatment of an acute
      temporomandibular disorder, we will address the problems of joint sounds, open
      and closed locking and psychological considerations. The management of pain and
      muscle spasm was considered in the previous paper.

PMID- 9515368
TI  - Progress in local anaesthesia.
AB  - Research into improving local anaesthetic agents and methods of delivering them
      in dental practice has been very slow. This article describes some of the
      progress that is being made in these areas.

PMID- 9515369
TI  - An update on the clinical documentation on currently used bone anchored
      endosseous oral implants.
AB  - In order to achieve safe and predictable results with oral implant therapy, the
      clinician has to rely on the scientific documentation when choosing a particular
      implant system. This review condenses the relevant clinical documentation on
      currently used endosseous oral implant systems and may help in the process of
      choosing an implant system.

PMID- 9515370
TI  - Locally delivered antimicrobials in periodontal therapy.
AB  - The rapid growth in our understanding of the pathogenesis of periodontal disease
      has led to a change in therapeutic emphasis, supplementing traditional, non
      specific, mechanical plaque control with a more focused targeting of pathogenic
      organisms. New topical preparations provide high antimicrobial doses at diseased
      sites without the systemic antibiotic loading which is now, in itself, a cause of
      concern due to the increasing tendency of micro-organisms to become resistant to
      antimicrobial agents. This article reviews the current methods of delivering
      antimicrobial agents to the gingival crevice and evaluates their roles in
      practical periodontal therapy.

PMID- 9515371
TI  - The role of soft tissues in the aetiology of malocclusion.
AB  - It is not always easy to discover the aetiology of malocclusion: only in about 5%
      of cases is a cause clearly identifiable. In this article, the various genetic,
      environmental and physical factors that may contribute to malocclusion are
      discussed.

PMID- 9515372
TI  - Periodontal treatment: non-surgical or surgical?
AB  - Successful treatment of periodontal disease depends upon the extent of disease,
      susceptibility of the individual to disease, and the motivation and expectations
      of the patient. The dental surgeon must balance these factors with the practical
      and financial constraints of treatment. Many dental practitioners find it
      extremely difficult to decide on a particular course of treatment: this article
      will help those in doubt to choose the treatment appropriate to their individual
      patients.

PMID- 9515373
TI  - The triangle of health: applications for general practice, Part 2: The dental
      team.
AB  - The triangle of health (physical, psychological and social) allows the dental
      health professional to appreciate the importance of the holistic view of health.
      The three dimensions of health are as applicable to the health and well-being of
      the dental health professional as they are to the patients they treat. Parallels
      between physical, psychological and social determinants of oral health for the
      patient are related to those for the health of the dental team members. Through
      an awareness of such matters dental health professionals can promote health for
      their patients and themselves.

PMID- 9515374
TI  - Historical development of whiteners: clinical safety and efficacy.
AB  - Since the introduction in 1989 of a home tooth-bleaching technique, the practice
      has become widespread in the USA. Safety concerns led the Food and Drug
      Administration (FDA) to temporarily ban sales in 1991 but the ban was later
      lifted, and the American Dental Association (ADA) now issues guidelines for
      safety and efficacy. Early information on safety of home bleaching products was
      often skewed because they were being compared out of context with those designed
      to be used only in the dental office. The early studies also failed to put the
      risks into perspective with the risks from other routine dental procedures. The
      risks are minimized with the systems supplied by dentists because he or she is
      able to diagnose any problems or special needs, to plan appropriate treatment and
      to fabricate, fit and adjust the prosthesis used to apply the material. A wide
      variety of disfigurements may now be treated successfully at home using
      preparations supplied by the dental practitioner.

PMID- 9515375
TI  - Implant-stabilized overdentures.
AB  - Implant-stabilized overdentures can be used successfully to restore the
      edentulous mouth, and there are many good reasons why this treatment should be
      selected in preference to using fixed dentures. However, as with any treatment,
      there must be a strong commitment to after care if the overdenture is to remain
      successful. This article discusses the advantages and disadvantages of using
      implants to stabilize overdentures, examines their success rates and discusses
      the extent of after care.

PMID- 9515376
TI  - Review of attendance behaviour.
AB  - Frequent dental check-ups correlate with good dental health. However, many non
      attenders see no need to attend a dentist until they have a problem that needs
      attention. Dental attendance may be stimulated by highlighting to the patient the
      reasons for future dental checks, persisting with recall messages and tailoring
      the recall method to individual patients.

PMID- 9515377
TI  - A review of orthodontic appliance problems in general dental practice.
AB  - Patients will often visit their general dental practitioner when experiencing
      problems with orthodontic appliances, even if they were referred to a specialist
      for treatment. Reassurance may be all that is necessary, but simple intervention
      may allow the treatment to continue with a minimum of interruption. This article
      is an overview of the common orthodontic appliance problems that may be
      encountered and provides practical advice on how to deal with them.

PMID- 9515378
TI  - Extra-osseous ameloblastoma: a case history.

PMID- 9515379
TI  - HIV-associated fulminating herpes zoster infection with alveolar necrosis and
      tooth exfoliation: a case report.
AB  - This paper presents a case of HIV-associated fulminating herpes zoster infection
      (HZI) that culminated in right mandibular necrosis and tooth exfoliation. The
      occurrence of such infection in immunosuppression and the impending clinical
      features are briefly reviewed and discussed.

PMID- 9515380
TI  - Proceedings of the Third Symposium on Digital Imaging in Dental Radiology,
      Noordwijkerhout, The Netherlands, 13 and 14 October, 1994. Abstracts.

PMID- 9515381
TI  - The use of radiographic techniques in the diagnosis and management of periodontal
      diseases.
AB  - Radiographs continue to play an important role in the diagnosis and management of
      periodontal disease although opinions as to the most appropriate form of
      assessment vary. It is important to recognize the limitations of each technique
      in terms of resolution, repeatability and accuracy so that radiographs can be
      correctly interpreted to the benefit of the patient. The value of intra-oral and
      panoramic radiography is reviewed, with particular reference to articles
      published over the past five years, followed by a consideration of developing
      computer-aided techniques which may, in time, prove of value to the dental
      practitioner in the diagnosis and management of periodontal disease.

PMID- 9515382
TI  - A comparison of detailed zonography with periapical radiography for the detection
      of periapical lesions.
AB  - The diagnostic accuracy of detailed zonography using the Scanora multimodal X-ray
      system was compared with that of periapical radiography. The study was based on
      the detection of periapical bone lesions at 259 dental sites distributed evenly
      throughout the dentitions of 164 patients. Each site was examined by periapical
      radiography and zonography, in parallel. The zonograms consisted of four detailed
      images that could also be read as stereopairs, in either the horizontal or
      vertical direction. Five observers evaluated the sites for the presence or
      absence of periapical osteolysis or sclerosis and apical widening of the
      periodontal ligament space for the whole dentition, and for three dental regions.
      ROC analysis revealed no significant overall or regional differences between the
      diagnostic accuracies of the periapical and zonographic techniques, regardless of
      whether the zonograms were read as sets of four images (multiview) or
      stereoscopic images. The sensitivity of periapical radiography was 72%, that of
      multiview zonography 88%, and that of stereoscopic zonography 85%. Specificities
      were 93%, 84% and 89%, respectively. The energy imparted during detailed
      zonography was 0.98 mJ. It is concluded that zonography is as good as periapical
      radiography for the detection of periapical pathology.

PMID- 9515383
TI  - Clinical and historical predictors of dental caries on radiographs.
AB  - This report evaluates the efficacy of the clinical predictors of caries proposed
      in the USA FDA guidelines for prescribing dental radiographs. The clinical
      findings that best associate with the presence of any caries where a history of
      pain, a defective restoration, unusual calcification, and an abutment tooth for a
      fixed or removable prosthesis. There is a group of measures of periodontal
      disease that were also weakly associated with the presence of caries. The best
      predictors of caries extending into the dentin were the presence of clinically
      defective restorations, a history of pain, and signs of periodontal disease.
      Proximal lesions are likely to appear on teeth with defective restorations,
      unusual calcification or large or deep restorations. The best predictors of
      radiographic root caries are periodontal findings such as furcation involvement,
      increased mobility, a history of periodontal therapy and gingival recession.
      While the specificities for these findings were generally high, the sensitivities
      and positive predictive values were usually under 50%, and often much lower. Thus
      these clinical findings cannot successfully be used as exclusive criteria for
      ordering radiographs for caries detection. Because caries is found fairly
      frequently, and because we are unable to identify tooth-specific criteria with
      clinically useful sensitivity and specificity values, these data support the FDA
      panel recommendation of bitewing examinations for all new patients and at
      periodic intervals for recall patients.

PMID- 9515384
TI  - Clinical and radiological findings related to treatment outcome in patients with
      temporomandibular disorders.
AB  - OBJECTIVES: To test the hypothesis that the outcome of temporomandibular
      disorders (TMD) is not influenced by condylar position, asymmetry, angle or
      structural bone changes. METHODS: Eighty consecutive patients (60 women, 20 men)
      with an age range of 6-81 years, referred to the Department of Stomatognathic
      Physiology, were included in the study. The patients were clinically and
      radiologically examined before and at least 1 year after treatment. RESULTS: The
      most common clinical diagnoses among the patients were TMD with a neuromuscular
      background in 35% and osteoarthritis in 21%. Seventy-two per cent of the patients
      were symptom-free or better, 24% unchanged and 1% worse 1 year or more after
      treatment. After treatment the bone structure of the TMJ was unchanged in 83% of
      the patients, in 12% erosions healed and in 5% erosions developed. Almost all
      patients had some degree of condylar displacement on tomography before treatment.
      In the majority the condylar position was unchanged after treatment. CONCLUSION:
      No single radiographic finding was found to be related to the treatment outcome
      and therefore plain radiography has a minor role in the management of TMD.

PMID- 9515385
TI  - Artefacts due to static electricity in a dental school.
AB  - The diagnostic usefulness of radiographs is diminished by errors of film
      handling, and retakes mean increased radiation doses. Avoiding artefacts due to
      static electricity is part of a quality assurance programme. The number of types
      of artefacts originating from static electricity in the Department of Radiology,
      School of Dentistry, Copenhagen, were recorded over a five-week period with low
      temperatures and low air humidity. During the period 3137 intra-oral and 638
      extra-oral films were processed by seven assistants and a number of trainees. A
      total of 48 artefacts on 47 extra-oral films was observed. The artefacts were
      classified into four types. Only one case of classical 'lightning' was found,
      while nine were of a hitherto undescribed type ('animals' or 'cactus flowers').
      The most common type appeared as dots arranged in straight lines; their origin
      was obscure, but it was suspected that they were caused by the processing
      machine. The one typical 'lightning' case occurred on a Status-X film, consistent
      with the theory that friction may be a causative factor. Although individual
      frequencies varied, all the radiography assistants and trainees were associated
      with the artefacts recorded.

PMID- 9515386
TI  - Facial dimple with accessory bone and teeth.
AB  - Accessory jaws (distomus), with or without teeth, rarely occur. This condition
      has been observed most commonly in association with lateral facial clefts. A case
      of a 6-year-old child with a unilateral facial dimple which is interpreted as a
      putative vestige of a lateral facial cleft and accessory maxilla is reported.
      Possible aetiology is addressed and previous cases are reviewed.

PMID- 9515387
TI  - The location and tracking of swallowed dental appliances: the role of radiology.
AB  - Two cases of swallowing mishaps, one involving a spoon-denture and the other an
      orthodontic partial arch wire, are reported. The former was recovered following
      interventional radiology, the latter by proctoscopy. The role of radiographic
      investigation and possible measures to prevent such potential life-threatening
      emergencies are discussed.

PMID- 9515388
TI  - Issues of justice in dentistry.
AB  - Perhaps the greatest appeal of holding individuals responsible for behavior
      related health problems arises from the idea of just desserts. Some individuals
      believe that a person who engages in risky behaviors deserves to suffer and
      should not expect pity. Health care providers with such opinions are not
      permitted to discriminate against patients in high-risk behavior groups. Some
      conduct may seem offensive or unnecessary to health care providers; however, they
      must care compassionately for those whose problems arise from such behaviors.
      Beneficence requires that dentists use their skills to help those in need, and
      set aside notions of punishing patients.

PMID- 9515389
TI  - Serious erythromycin interactions caused by inhibition of drug metabolism in the
      liver.

PMID- 9515390
TI  - Reducing the failure potential of ceramic-based restorations. Part 1: Metal
      ceramic crowns and bridges.

PMID- 9515391
TI  - Dentin bonding: past and present.
AB  - Dentin-bonding agents have changed dramatically since being introduced. The large
      number of these products, as well their dynamic nature and myriad clinical uses,
      make it difficult for clinicians to understand how they work and when to use
      them. Sequential development of dentin-bonding agents from the mid-1950s to the
      present is described. Information also is provided about current popular bonding
      products and new clinical applications.

PMID- 9515393
TI  - Nitrous-oxide use. I. Risk of potential exposure and compliance among Nebraska
      dentists and dental assistants.
AB  - Patterns of nitrous-oxide (N,O) use among Nebraska dentists and dental assistants
      are reported. More than 800 respondents answered questions relating to risk of
      N,O exposure and compliance with N,O standards in the dental office: 73 percent
      of these dental practices using N,O have a state-registration permit. Dentists
      and dental assistants (from registered and unregistered practices) reported risk
      of exposure differently. Important compliance issues emerged (the average
      compliance rate was 9 on a scale of 17). Most N,O users have scavenging systems,
      but they are not properly operated. Few dental practices test for leaks or
      conduct N,O-monitoring tests. By complying with the recommendations for N,O
      administration, dental-care workers can minimize their risk of exposure.

PMID- 9515392
TI  - Composite bonding to dentin and enamel: effect of humidity.
AB  - The effect of oral ambient air on shear strength to etched enamel and dentin was
      determined for OptiBond FL (Kerr Corp., Orange, CA) and Prodigy resin composite
      (Kerr Corp.). Enamel and dentin specimens of extracted human teeth were treated
      both in a dry environment and after exposure to oral humidity according to
      manufacturer's instructions. Shear strengths of this system are 22.6 MPa for
      etched, dry enamel; 22.2 MPa for etched, wet enamel; and 18.4 MPa for etched, dry
      or wet dentin. Differences in shear strengths between the wet and dry enamel or
      the wet and dry dentin were not significant. Multiple Student's t-tests were used
      for statistical analysis. Fracture modes for all specimens were examined under a
      stereomicroscope. Within the parameters of this in vitro study, OptiBond FL was
      not affected by oral humidity.

PMID- 9515394
TI  - Retentive properties and film thickness of 18 luting agents and systems.
AB  - In the past, retention of castings depended on mechanical interlocking or
      adhesion to enamel and dentin by means of chelation in the case of some cements.
      Some new luting agents adhere to metal and tooth structure. The era of bonded
      casts for crowns and bridges has arrived through a combination of dentin primers
      and luting agents that bond to enamel, dentin, and precious and nonprecious
      metals. For a few systems, the retentive forces (in an otherwise nonretentive
      experimental design) more often than not exceeded tooth strength.

PMID- 9515396
TI  - Antimicrobial management of third molars: survey results for military dentists.
AB  - In a survey of military dentists to examine use of antimicrobial agents in the
      management of third molars, questions addressed use of antibiotics and an
      antimicrobial rinse in treating pericoronitis and third molar extractions.
      Results were compared with information from a literature review. According to the
      survey, a majority of clinicians use antibiotics to treat pericoronitis but not
      surgical extraction of asymptomatic dental impactions. About 60 percent of
      respondents use a preoperative rinse with chlorhexidine in treating the third
      molar conditions discussed. A postoperative rinse with chlorhexidine was used
      less frequently. Half the respondents listed medicolegal factors in their
      decisions.

PMID- 9515395
TI  - Optical densities of dental resin composites: a comparison of CCD, storage
      phosphor, and Ektaspeed plus radiographic film.
AB  - Density versus exposure was determined for digital and film radiographic images
      of various thicknesses of six dental resin composites. The curves were relatively
      parallel; saturation at the black end of the contrast scale occurred at lower
      exposures with Computed Dental Radiography (CDR, Schick Industries, Long Island
      City, NY) than with the Sens-A-Ray (Regam AB, Sundsvall, Sweden). Ektaspeed Plus
      film (Kodak Dental Products, Rochester, NY) was the least sensitive modality
      tested. The DIGORA storage phosphor system (Soredex-Orion, Helsinki) had a wide
      exposure latitude with significantly less steep characteristic slopes than for
      images from the charge-coupled devices (CCDs). Slopes generated for the Sens-A
      Ray and the CDR were not significantly different. Slopes generated for each resin
      composite were not significantly different for each of the modalities. Relative
      radiopacities of the resin materials with respect to each other were constant
      across all modalities; hence, in these systems, sensor type is unlikely to affect
      differentiation between resin composites and dental enamel or recurrent caries.

PMID- 9515397
TI  - A multidisciplinary approach to restoring a partially edentulous patient.
AB  - A 56-year-old woman had missing teeth, severe bone loss with mobile teeth, an
      anterior crossbite, collapsed arches, and maxillary midline deviation. She was
      stabilized periodontally, then a dental implant was placed for anchorage. After
      selected teeth were extracted, full orthodontic treatment was initiated, and
      restorative treatment was provided with the implant as an abutment.

PMID- 9515398
TI  - A brief survey of herbal medicines and other remedies.

PMID- 9515399
TI  - Ethics and direct marketing to patients.

PMID- 9515400
TI  - General dentists and periodontists have key roles in soft-tissue management.
      Interview by J. Frank Collins.

PMID- 9515401
TI  - Meeting the educational needs of patients with oral lichen planus.
AB  - Lichen planus is a chronic oral disorder that is often painful and annoying. The
      patients have been described as usually over 50 years old, with a high
      educational level, anxious and high-strung. In previous research studies, these
      patients have reported unusual and highly stressful life events. Because dentists
      are in a position to advise their patients about chronic illness, this study was
      designed to (1) determine what information was given to lichen planus patients by
      their dentists; (2) determine what questions the patients asked their dentists;
      and (3) assess what educational materials would be helpful for this group of
      patients. A survey was sent to 151 biopsy-confirmed lichen planus patients, with
      a response rate of 55 percent. The results indicated that the patients were
      concerned about the possibility of malignancy and of contagion, and that they
      were frustrated by the lack of available patient education.

PMID- 9515402
TI  - Topical fluorides: efficacy, administration, and safety.
AB  - Fluoride's role in decreasing dental caries has been recognized for decades. The
      professional fluoride treatment has recently been augmented with home-use
      fluoride products. The introduction of many attractive products makes it
      difficult for dental professionals to know which are effective. Both professional
      and home-use products are described, as are proven techniques for their use.
      Recognition of fluoride toxicity, and its prevention and treatment, are also
      discussed.

PMID- 9515403
TI  - Hypersensitivity and pain induced by operative procedures and the "cracked tooth"
      syndrome.
AB  - Various dental conditions are responsible for tooth hypersensitivity and pain.
      They include hypersensitive dentin; the "cracked tooth" syndrome; pulp and
      periapical irritation, inflammation and/or degeneration; barodontalgia
      (aerodontalgia); and periodontal pathoses, particularly the pulpal-periodontal
      syndrome. Each operative condition is reviewed with respect to its etiology,
      symptomatology, and diagnosis. Some treatment recommendations are made to prevent
      or reduce symptoms.

PMID- 9515404
TI  - Accelerated healing of gingival incisions by the helium-neon diode laser: a
      preliminary study.
AB  - Fifty-two extraction patients had one of two gingival flap incisions lased with a
      helium-neon (He-Ne) diode laser at a fluence (energy density) of 1.2 J/cm. The
      rate of relative healing was evaluated clinically and photographically. Seventy
      nine percent of the lased incisions healed more quickly than did the control
      incisions. No significant difference in healing was noted when patients were
      compared by age, gender, race, or anatomic location of the incision. This study
      suggests that He-Ne diode lasers, at the above energy level, appear to increase
      the rate of gingival wound healing in humans, without negative side effects.

PMID- 9515405
TI  - Odontogenic keratocyst.
AB  - Odontogenic keratocysts comprise approximately eight percent of all jaw cysts and
      have a significant recurrence rate. Following a review of the literature, the
      treatment of two patients with such cysts is described.

PMID- 9515406
TI  - Talon cusp with associated adjacent supernumerary tooth.
AB  - Talon cusp may occur with other dental anomalies. A case is reported in which
      talon cusp is associated with a supernumerary tooth, suggesting genetic
      inheritance as a causative factor.

PMID- 9515407
TI  - Porcelain veneer repair of prostheses.
AB  - Metal-ceramic restorations have the potential to fracture. Repairing porcelain
      restorations creates a serious dilemma for the restorative dentist. The most
      common repair technique is one using composite resin; porcelain veneer provides
      an alternative.

PMID- 9515408
TI  - Influence of root anatomy on periodontal disease.
AB  - One of the essential elements of periodontal therapy is long-term maintenance.
      Anatomic factors that favor localized plaque accumulation may contribute to the
      progression of disease. The purpose of this investigation was to evaluate the
      influence of root concavities on the severity of furcation involvement.
      Measurements were recorded clinically at the time of surgical treatment.
      Statistical analysis revealed no significant association between the degree of
      root concavity and the severity of furcation involvement.

PMID- 9515409
TI  - The top 50 drugs dispensed in pharmacies in 1996.

PMID- 9515410
TI  - Informed consent across cultures.

PMID- 9515412
TI  - The role of tobacco use in periodontal diseases: a literature review.
AB  - This article surveys early and current research on the relationship between
      smoking and various aspects of dental health. Results of early studies on the
      prevalence of periodontal diseases in smokers, which were often contradictory,
      are discussed briefly, and more recent research on the effects of tobacco on the
      periodontium is presented. This includes research examining the relationship-
      between smoking and the various indicators of periodontitis, such as bone and
      tooth loss. Studies examining the effect of smoking on the outcome of periodontal
      therapy, and ways in which tobacco may be harmful are also reviewed, as are the
      effects of smokeless tobacco on the periodontium. It is suggested that a separate
      category for smoking-associated periodontitis be created.

PMID- 9515411
TI  - New guidelines for the prevention of bacterial endocarditis. American Heart
      Association.

PMID- 9515413
TI  - The general practitioner's perspective of the etiology, prevention, and treatment
      of dry socket.
AB  - Alveolar osteitis (AO) is the most common postoperative complication following a
      tooth extraction. This article focuses on its etiology and contributing factors.
      It is intended to assist the general practitioner in reducing the incidence of AO
      in his or her practice. The article includes summaries of current preventive and
      treatment measures.

PMID- 9515414
TI  - The reinforced natural tooth pontic.
AB  - This article describes an esthetic alternative for the periodontally compromised
      dentition. It involves a technique for using a natural tooth pontic (bonded with
      resin composite and reinforced by an intracoronal orthodontic wire), for
      replacing an anterior tooth in a periodontally compromised, mobile dentition.
      Following extraction and root resection of the maxillary central incisor, recess
      grooves were placed into the pontic and the adjacent abutment teeth. Intracoronal
      round orthodontic wire (0.032) was embedded into these preparations and bonded
      with acid-composite, which increases the retention of the tooth pontic.

PMID- 9515415
TI  - Adherence of two film-forming medications to the oral mucosa.
AB  - This study provides a comparison among 10 patients of old and new formulas of
      Zilactin (Zila Pharmaceuticals, Phoenix). The original formula contained tannic
      acid; the new formula replaced tannic acid with benzyl alcohol as the active
      ingredient. The U.S Food and Drug Administration's (FDA) ruling that tannic acid
      must be eliminated as the active ingredient from the Zilactin formula was the
      reason for the change. In the study, no side effects were reported for either
      formula, except for a minor burning sensation at the time of application.
      Moreover, the new Zilactin formula, on average, provided a statistically
      significant rate of adherence of 21 percent to the oral mucosa.

PMID- 9515416
TI  - Complete prosthodontic rehabilitation of a patient with Graves' disease.
AB  - Graves' disease is the most common form of hyperthyroidism. A brief summary of
      hyperthyroidism is given with the common symptoms that characterize a thyroid
      storm. This is followed by a case report of a method of restoring dental health
      to a patient with Graves' disease.

PMID- 9515417
TI  - Clinical use and potential biohazards of nitrous/oxide oxygen.
AB  - This article examines the worldwide literature for information regarding the
      potential adverse effects of nitrous oxide on chronically exposed personnel. This
      research convincingly demonstrates the lack of substantiation for these concerns.
      Biologically correlated standards for exposure still need to be established.
      Nitrous oxide has never been implicated to be harmful in any way to the patient.

PMID- 9515418
TI  - Actinic cheilitis: a premalignant condition.
AB  - Actinic cheilitis is a premalignant, irreversible disease that frequently affects
      the vermilion border of the lower lip. Since there is no correlation between
      clinical appearance and histologic aggressiveness, a biopsy is mandated. A
      vermilionectomy procedure is described, as well as the most frequently
      encountered complications.

PMID- 9515419
TI  - Tongue piercing: a concern for the dentist.
AB  - "Body art" is a relatively recent fashion in the western world, but appears to be
      gaining in popularity. It involves tattooing, scarification, and the wearing of
      jewelry in unconventional places on the body. This article discusses one form of
      "body art"--tongue piercing. The presence of metal jewelry in the oral cavity
      presents oral hygiene problems, as well as the risk of the development of
      undesirable sequelae. It may become the responsibility of the dentist to advise
      the patient on the care and maintenance of this jewelry, and to treat
      complications.

PMID- 9515420
TI  - Suppression and prevention of the gag reflex with a TENS device during dental
      procedures.
AB  - Individuals who are prone to gagging and apprehension during dental treatments
      present a problem for the clinician and themselves. Patients may delay prescribed
      therapy or interfere with the fabrication of accurate oral impressions and
      diagnostic radiographs, because of this fear. The common wisdom has been to try
      one of the following procedures: (1) distraction of the patient, (2) forced
      respiration, (3) induced lagophthalmus, or (4) hypnosis. A preventive approach
      suggests that the sensory stimulation of the cranial nerves of the superior
      laryngeal nerve branch, (Cr N, IX, pharyngeal branch of X, Cr. N. V, and Cr N.
      X.) would block the physiologic response of gagging and retching.

PMID- 9515421
TI  - Technique sensitivity of dentin bonding.

PMID- 9515422
TI  - New drug approvals in 1996.

PMID- 9515423
TI  - Delivering bad news to dental patients.
AB  - Most dentists are accustomed to reporting to a patient that he or she has two new
      carious lesions, and patients accept such news relatively easily. A diagnosis of
      periodontal disease requiring multiple extractions and denture construction is
      less readily assimilated; accordingly, providers usually take more time and care
      in explaining this situation. A diagnosis of carcinoma, which a dentist seldom is
      required to deliver, cannot be imparted in the same manner in which one would
      reveal a diagnosis of caries or of periodontal disease. A compassionate,
      measured, sensitive, and private discussion between a dentist and a patient with
      a serious diagnosis serves as the first step of a journey that is likely to
      result in substantive changes in that patient's life.

PMID- 9515424
TI  - Comprehensive orofacial pain analysis: a structured approach to patient history.
AB  - A structured approach to pain analysis is described. This format for obtaining a
      complete history is useful to persons involved in the diagnosis and management of
      painful conditions involving the head and neck. Key components and rationale for
      their inclusion in a thorough evaluation process are discussed.

PMID- 9515425
TI  - A triply avulsed tooth.
AB  - Canada has a rich hockey tradition. Accordingly, Canadian dentists are well
      acquainted with tooth avulsion, although the emergence as the mouth guard as an
      essential component of protective sports equipment has reduced its incidence.
      Practitioners occasionally examine patients who have lost teeth as a result of
      accidents. In this unusual case, a patient's tooth was removed 3 times in 12
      hours.

PMID- 9515426
TI  - Common causes of nondental facial pain.
AB  - General dentists often are among the first to be consulted when a patient
      experiences facial pain. Frequently, the cause is obvious. However, there are
      cases in which the etiological factor is not so evident. Often, in an attempt to
      help relieve a patient of pain and suffering, irreversible, invasive procedures
      are undertaken that prove only to increase the patient's pain and the
      practitioner's frustration. Three common pain syndromes that may be confused with
      odontogenic pain are discussed: temporal tendinitis, Ernest syndrome, and
      atypical trigeminal neuralgia. The symptoms, diagnostic procedures, and
      treatments for all three disorders are presented, as is a newly described muscle,
      the zygomandibularis.

PMID- 9515427
TI  - Guidelines for the restoration of Class V lesions.
AB  - Approximately 18 percent of all permanent teeth have Class V lesions. In
      addition, the prolonged retention of teeth in an increasingly older population is
      expected to increase the prevalence of Class V lesions. Much has been written
      about the merits of various techniques for restoring such lesions, but little
      information is available comparing and contrasting all the material and
      procedural options available to the general dentist. Etiologies, indications for
      treatment, and restorative materials are discussed to provide guidance in
      planning treatment. A diagnostic decision tree is proposed for this dynamic area
      of restorative dentistry.

PMID- 9515428
TI  - Sjogren's syndrome: a challenge for dentistry.
AB  - Sjogren's syndrome presents dentists with many challenges, from diagnosis to
      therapy. The secondary effects of xerostomia cause a spectrum of oral problems,
      including caries, candidal infection, and inflammation of the oral mucosa. The
      oral signs and symptoms may be the first manifestations of systemic aspects of
      the disease. Sjogren's syndrome requires both dental and medical management, and
      a program of home care.

PMID- 9515429
TI  - Pregnancy tumors: a case report.
AB  - Pregnancy tumors are reactive, inflammatory lesions that develop as a result of
      bacterial irritation to the hormonally altered gingival tissues during pregnancy.
      A case report is presented of an unusually large pregnancy tumor. Etiologic
      considerations and treatment options are discussed.

PMID- 9515430
TI  - Effects of CO2 laser irradiation on tooth-root cementum.
AB  - With the aging of the American population and the endemic problem of gingival
      recession, patients will inevitably suffer from greater exposure of root surfaces
      and therefore will be more likely to develop root caries. The treatment of root
      caries is often frustrating. Traditional biomaterials used for the restoration of
      enamel caries have been less than satisfactory when margins of a cavity are
      adjacent to cementum. Although topical fluoride gels, toothpastes, and rinses
      have been used to prevent or to inhibit the development of root caries, there is
      a problem of access to the proximal surfaces. Consequently, the development of
      better methods to facilitate the prevention of root caries has become an
      important issue in dentistry.

PMID- 9515431
TI  - The hypomobile temporomandibular joint.
AB  - The hypomobile (restricted) temporomandibular joint (TMJ) is usually caused by a
      restricted joint capsule or by an anteriorly displaced disk. Here, painful
      unilateral hypomobility (19 mm jaw opening), with normal disk position, caused by
      voluntary immobilization after a dental procedure, was the presenting symptom.
      Management included inflammation control, TMJ manipulation (mobilization), and
      lateral pterygoid muscle relaxation. Inflammation and pain were alleviated by
      nonsteroidal anti-inflammatory drugs (NSAIDs) and local TMJ ice massage. TMJ
      mobilization was performed at every visit, to tear joint capsule adhesions and to
      realign collagen fibers. Exercise consisted mainly of resistive opening (the
      patient resists an upward force applied to the chin), with the jaw maintained at
      full opening. This produced lateral pterygoid muscle relaxation at full length,
      aiding in the restoration of a pain-free 44 mm opening.

PMID- 9515432
TI  - Orthodontics, prosthodontics, and periodontics: a multidisciplinary approach.
AB  - Congenitally missing lateral incisors are not a rarity in any dental practice,
      yet the treatment for this condition is usually a challenge. Various treatment
      possibilities and their indications, contraindications, and problems are
      discussed. A case report involving orthodontic treatment followed by placement of
      implants and single-tooth porcelain-fused-to-metal crowns.

PMID- 9515433
TI  - Tooth-colored inlays: new cementation technique.
AB  - A new technique for tooth-colored inlay cementation is introduced. Dual-cure
      fully filled restorative resin Sono-Cem (ESPE America, Norristown, PA) was used
      to cement tooth-colored restoration. A specially designed wooden tip in the
      gently vibrating Profin handpiece (Dentatus USA, New York) may be considered an
      excellent instrument for cementing porcelain and composite inlays with Sono-Cem
      cement. Also, a wide variety of diamond/tungsten plated abrasive Lamineer tips in
      a Profin Handpiece may be used for tooth preparation as well as for finishing
      restorations.

PMID- 9515434
TI  - Complaint review procedures of state licensing boards.
AB  - In the highly litigious society in which we practice, situations all too
      frequently arise in which a dentist and a patient disagree. The disagreement may
      be as minor as a misunderstanding regarding fees charged for services rendered,
      or as substantial as that resulting from an injury secondary to dental treatment.
      Regardless of the exact nature of the incident, it nonetheless may result in the
      filing of a complaint by the aggrieved patient with the state board of dentistry
      against the treating clinician. This article explains the process leading to the
      resolution of a complaint.

PMID- 9515435
TI  - Dental considerations of patients taking appetite suppressants.

PMID- 9515436
TI  - Extra protection is prudent, not discriminatory.

PMID- 9515437
TI  - Ethics, or opinion?

PMID- 9515438
TI  - Exploring ethical foundations.

PMID- 9515439
TI  - A single-component bonding system microleakage study.
AB  - The microleakage of a one-component bonding system is compared to a two-component
      system and a control. Class V cavity preparations were prepared in extracted
      teeth under high speed and water coolant so that incisal/occlusal margins were in
      enamel, and gingival margins were in dentin. Group I was restored with composite
      and no bonding agent; Group II was restored with Prime and Bond and composite,
      and Group III was restored with ProBond and composite. All specimens were
      thermocycled in fuchsin dye to evaluate the degree of microleakage. Significant
      differences were observed between the no bonding agent group and the Prime and
      Bond and ProBond groups. The results indicate that the one-step dentin bonding
      system has the ability to prevent microleakage effectively at both composite
      enamel and composite-dentin tooth surface interfaces.

PMID- 9515440
TI  - A two-year clinical evaluation of TPH for restoration of Class II carious lesions
      in permanent teeth.
AB  - To evaluate the clinical suitability of a barium silicate-filled composite (TPH)
      for restoration of posterior teeth, 50 Class II restorations were restored in 36
      patients. Restorations included 22 molars and 32 premolars. Cavity preparations
      were protected with calcium hydroxide or a resin-modified glass ionomer cement,
      or both. Enamel was etched for 30 seconds with 37 percent H3PO4. All dentin
      surfaces were treated with a dentin bonding system that was placed, cured, and
      restored in 2 microns increments. The restorations were finished using diamond
      burs, polishing points, and paste. Evaluation periods were at zero (50
      restorations), 6 months (35 restorations), 1 year (31 restorations), and 2 years
      (29 restorations), using the USPHS System and M-L indirect scale. At zero time,
      50 restorations were scored "a" in all categories by using two independent
      evaluators. After 6 months, 35 restorations were graded with one "a" in
      postoperative sensitivity. After 1 year, 31 restorations were evaluated with one
      additional "b" for marginal integrity. After 2 years, 2 additional "b" for
      marginal integrity and 1 "b" for surface staining were noted. No "c" was observed
      in any categories throughout this study. Wear analysis revealed, on average, 2
      microns of wear after 6 months, 7.8 microns of wear after one year, and 10.3
      microns of wear after 2 years.

PMID- 9515441
TI  - Trismus: causes, differential diagnosis, and treatment.
AB  - Successful treatment of trismus depends upon prompt recognition of its cause and
      the initiation of appropriate management. Otherwise, trismus may lead to
      permanent functional impairment. Differential diagnosis and modes of treatment
      are reviewed.

PMID- 9515442
TI  - Clinical research on bonded amalgam restorations. Part 1: SEM study of in vivo
      bonded amalgam restorations.
AB  - Exfoliated deciduous teeth, in which bonded or nonbonded amalgams had been placed
      two to three years previously, were examined directly and indirectly with the use
      of a scanning electron microscope (SEM). Bonding resin was found in the interface
      between the amalgam and the tooth structure, frequently obliterating the
      microspace. Several materials now are available that bond amalgam to tooth
      surfaces with bonding strength exceeding 10 MPa. Amalgam can be retained in
      preparations without undercuts, or in pits and fissures without any tooth
      preparation. The article consists of two parts: in part 1, results of a pilot
      study on bonded amalgam-tooth interfaces is presented. In part 2, the authors
      discuss further studies and clinical technique. Commercial products are compared;
      and other clinical trials now in progress, concerning amalgam bond strength
      adhesion and ability to eliminate microspace, are discussed.

PMID- 9515443
TI  - Clinical research on bonded amalgam restorations. Part 2: Further studies and
      clinical technique.
AB  - In vitro studies show that the adhesive amalgam technique is superior to the
      nonadhesive technique. Also, early clinical results indicate that the adhesive
      technique can eliminate the microspace between amalgam and tooth. And, it can
      retain amalgam on unprepared occlusal surfaces of molars and premolars, sealing
      the fissures. Moreover, amalgam can be retained in preparations without
      undercuts. Early results indicate in traditional preparations, the adhesive
      technique appears to be at least equivalent to nonadhesive technique.

PMID- 9515444
TI  - Radiotherapy for head and neck neoplasms.
AB  - The use of radiotherapy has proven to be an effective technique in the control
      and cure of head and neck neoplastic disease. Unfortunately, radiotherapy also
      has a significant negative impact on the oral health of patients and the dental
      care they require. For dental professionals to be valuable members of the
      oncology treatment team, they must have a sound understanding of the dental needs
      and proper treatment of these patients. As background information, a brief
      overview of ionizing radiation and its effect on mammalian tissue is presented.
      In addition, the oral complications of ionizing radiation are reviewed, and
      prevention and treatment protocols discussed.

PMID- 9515445
TI  - Medication-induced gingival enlargement: a clinical review.
AB  - This review discusses the etiology and treatment of gingival hyperplasia. It
      cites evidence that medications such as phenytoin, an anticonvulsant;
      cyclosporine, an immunosuppressant; and numerous calcium channel blocking agents
      have been shown clinically and histologically to produce analogous gingival
      enlargements. A multiphasic approach to treating disfiguring gingival hyperplasia
      through mechanical and chemical plaque control, in conjunction with the surgical
      removal of the hyperplastic tissue, is discussed.

PMID- 9515446
TI  - The storage stability of dental composite resins: seven-year results.
AB  - The properties of chemically cured and light-cured composite resins were recorded
      at baseline and at intervals over seven years, while the materials were exposed
      to controlled storage conditions as well as to various conditions typical of
      clinical situations. For chemically cured resins in clinical conditions,
      mechanical properties decreased, and working and setting times increased over
      four years; if refrigerated (controlled), properties remained constant past seven
      years. For light-cured resins, test results were constant over the entire seven
      year test period regardless of storage conditions. An accelerated aging protocol
      was developed to allow for the evaluation of the relative storage stability of
      new and similar materials.

PMID- 9515447
TI  - Localized osteomyelitis following a restorative procedure.
AB  - This case report describes a localized interproximal soft-tissue lesion in the
      anterior maxillary area that may have been caused by a composite curing light.
      Following clinical examination and histological analysis, the diagnosis of acute
      osteomyelitis was made. Palliative treatment and debridement resulted in complete
      resolution.

PMID- 9515448
TI  - Higher education funding review.

PMID- 9515449
TI  - No surprise in findings.

PMID- 9515451
TI  - Plain English please.

PMID- 9515450
TI  - Interesting issues.

PMID- 9515452
TI  - Frankenstein's nurse! What are schools of nursing creating?
AB  - The research presented in this paper examines the socialisation of nursing
      students under the current educational arrangements and the way in which it
      creates nurses who assign high status to technological expertise and its
      manipulation, while regarding many of the traditional, more 'basic', nursing
      skills as being of low status. Such a professional outlook has serious
      implications for areas of nursing practice where technology is largely
      inappropriate and where care of the body dominates practice (such as in aged
      care). In a longitudinal study which followed student nurses from neophyte to
      graduand status, results showed that intentions to work in aged care decrease as
      students progress through their pre-service programs. At the same time, however,
      these students come to regard areas that require a manipulation of technology,
      such as is perceived in surgical wards and intensive care, as the 'real' role of
      nursing. Structures which guide students through the socialisation process, (i.e.
      the curriculum and teaching staff) were examined regarding their contribution to
      the establishment and maintenance of this culture. The findings of this study
      have important implications for the future of quality nursing in areas like aged
      care--as well as for the future success of nursing in its quest to be regarded as
      a 'true', autonomous profession.

PMID- 9515453
TI  - Spirituality and nursing: toward an ontological understanding.
AB  - The epistemological basis for nursing knowledge and practice is now well
      established. However, the ontological dimensions of nursing have not been as
      fully considered. Although the spirituality of people is receiving attention in
      nursing literature, a deeper understanding of its relevance as an ontological
      dimension of nursing, is needed. This paper examines reasons and strategies for
      emphasising spirituality as an ontological component of nursing.

PMID- 9515454
TI  - Skin cancer prevention: still missing the target!
AB  - Skin cancer is a significant public health issue in Australia due to the
      preventable nature of the disease, its high incidence rate, and its effects on
      mortality and morbidity. What public health strategies are being used to target
      this disease, and is this important health issue being dealt with adequately?
      This paper highlights three areas where skin cancer prevention programs have
      failed. Firstly, health education is not successful for individuals in low socio
      economic groups where financial and social resources are limited. Secondly, the
      common ideology that equates a suntan with youth, vigour and health needs to be
      challenged. Finally, there has been a failure to reorient and use the significant
      resources available in our health institutions for skin cancer education and
      prevention.

PMID- 9515455
TI  - The contested work place: reactions to hospital based RNs doing degrees.
AB  - This article focuses on the findings from a research project investigating
      hospital based RNs' attitudes and reactions to nursing degrees. Specifically, the
      results describe the tension and hostility which was predominating in clinical
      settings when the research was conducted. The reactions of both degree and non
      degree nurses to the changes in nursing education are put forward. It is
      suggested by the author that while work environments have been characterised by
      destructive behaviours, nurses' verbalising their reactions to this situation,
      have provided a platform to deal more constructively with personal and
      professional change.

PMID- 9515456
TI  - Mentoring relationships of New Zealand nurses: results of an empirical study
      (Part 2).
AB  - The first national study of mentoring relationships of New Zealand nurses used
      three issues from the descriptive literature as its conceptual framework. The
      results and discussion of the study are reported in part two. Results
      demonstrated that moderate levels of mentoring according to Kram's (1985)
      typology occurred amongst nurses and that they had many supportive relationships,
      mainly with women who were peers. The characteristics of nurses' mentoring
      relationships did not differ significantly from mainstream empirical data when
      factors such as gender, organisational status, age differences and duration of
      relationships were considered. Concerns about the future direction of mentoring
      research and in particular about recent international literature calling for the
      development of a separate mentoring theory for women conclude the article.

PMID- 9515457
TI  - Negotiated care--fundamental to nursing practice.
AB  - This paper focuses on negotiation in nursing. It suggests that negotiation, in
      the form of negotiated care, is a key element of nursing practice in the many
      contexts in which it takes place. To support this statement the process of
      negotiated care is illustrated by three examples. These examples portray
      negotiated care as it occurs between nurse manager (or leader) and nurse
      clinicians, in an interdisciplinary context, and between nurses, other health
      practitioners and patients/relatives. These examples demonstrate that negotiation
      which is aimed at achieving quality patient care pervades nursing practice.
      Nevertheless, it is suggested that nurses often do not recognise the centrality
      of negotiation in their nursing practice, nor are its implications for long-held
      beliefs about the role of the nurse considered. This paper also suggests that the
      successful outcome of negotiation in the context of nursing is dependent on
      nurses' confidence in, and their ability to articulate their knowledge about,
      nursing practice. It also relies on their commitment to the therapeutic nature of
      nursing practice and nurses' awareness that their practice is an essential
      component to patient care. The specialist nature of negotiation in nursing care,
      and its fundamental role in the care process, suggests that negotiation in
      nursing is more accurately termed negotiated care.

PMID- 9515458
TI  - Web-site review: occupational health and safety.

PMID- 9515460
TI  - Ageing--change of attitude needed.

PMID- 9515459
TI  - Meningococcal disease in Australia.

PMID- 9515461
TI  - Innovative leadership.

PMID- 9515462
TI  - Protocols for practice: a tool for bringing research to patient care.

PMID- 9515465
TI  - Hantavirus pulmonary syndrome: implications for critical care nurses.

PMID- 9515466
TI  - Sternal wound infection: a case study of a devastating postoperative
      complication.
AB  - Patients with a sternal wound infection are often admitted to the ICU or to a
      telemetry unit. The case of MW is extreme; most patients with a sternal wound
      infection can be successfully treated with antibiotic therapy and debridement.
      However, this case illustrates what devastating effects a sternal wound infection
      can have and the importance of nursing care and prevention. Nurses have a key
      role in minimizing the severity of sternal wound infection by being aware of the
      risk factors and providing thorough discharge teaching to patients so that signs
      and symptoms are reported early.

PMID- 9515467
TI  - Renal replacement therapy in critical care: implementation of a unit-based
      continuous venovenous hemodialysis program.
AB  - Implementing a program as complex as continuous venovenous hemodialysis without
      the involvement of nephrology nurses is a challenge. However, with proper
      planning, appropriate staff support, and the ability to make changes as
      implementation proceeds, a successful program can be developed. Our reward is
      that we are now able to offer a therapy that is important and potentially
      lifesaving to those critically ill patients with renal failure who are unable to
      tolerate intermittent hemodialysis.

PMID- 9515468
TI  - Protecting ICU patients from nosocomial infections: practical measures for
      favorable outcomes.

PMID- 9515469
TI  - How to succeed in job interviewing.
AB  - Effective interviewing skills are critical for any nurse seeking a position in
      today's challenging job market. The successful applicant is more than just
      poised, appropriately dressed, and courteous. Jobs go to applicants who are well
      prepared, qualified, confident, and motivated. To win a competitive edge,
      convince employers of your genuine desire for the position, your ability to do
      the job, your positive attitude, and the strengths that distinguish you from
      other applicants.

PMID- 9515470
TI  - Management of children in status asthmaticus.
AB  - Children admitted to the ICU with status asthmaticus require continuous nursing
      assessment of respiratory status and monitoring of the response to therapy.
      Nurses must be aware of the progression of respiratory distress and of the
      expected response to treatment and the side effects that can occur with each
      therapy. By assuming a greater responsibility in the care of the child with
      status asthmaticus, critical care nurses can improve the quality of care for
      these patients.

PMID- 9515471
TI  - Laryngeal mask airway: indications and management for critical care.
AB  - The laryngeal mask airway is the newest tool for airway management during the
      perianesthesia period. This device has joined other resuscitation equipment on
      emergency carts. Critical care nurses must be prepared to care for patients for
      whom laryngeal mask airways are indicated and used. A solid understanding of the
      purpose and placement of the laryngeal mask airway is necessary for safe removal
      of the device. Policies and procedures should be developed to define standards of
      care and responsibilities for care of patients with a laryngeal mask airway.

PMID- 9515472
TI  - Life-saver or money waster? The PA catheter goes under the microscope. Interview
      by Alison Paladichuk.

PMID- 9515474
TI  - Ask the experts. Maintaining pulmonary artery catheter patency.

PMID- 9515473
TI  - Pulse oximetry.

PMID- 9515476
TI  - The request.

PMID- 9515477
TI  - Intravenous conscious sedation. Physiologic, pharmacologic, and legal
      implications for nurses.
AB  - Nurses with proper additional training can safely assist in the care of patients
      receiving intravenous conscious sedation for a variety of procedures. Sedation
      exists along a continuum, with subtle differences between lighter and deeper
      levels of sedation. The primary goal of conscious sedation is to achieve a
      minimally sedated patient with intact protective airway reflexes. Pharmacologic
      agents may provide anxiolysis, amnesia, sedation, or analgesia. Legal
      considerations, policy development, and educational requirements for nurses
      choosing to practice in this expanded role are examined.

PMID- 9515478
TI  - The effects of intravenous solutions on fluid and electrolyte balance.
AB  - To maximize the benefit and minimize the adverse effects of fluid and electrolyte
      therapy, it is critical for clinicians involved to be knowledgeable about the use
      of parenteral fluids as maintenance therapy, replacement therapy, or as a vehicle
      for drug administration. All clinicians involved in the administration of
      parenteral therapy must understand the physiologic processes that regulate fluid
      and electrolyte balance, the proper dosing of these nutrients, and the fluids
      used to manage patients' fluid and electrolyte balance. The role of i.v.
      solutions in fluid and electrolyte balance is reviewed, and the value of the i.v.
      nurse specialist as a member of the interdisciplinary team that safely and
      effectively administers fluid and electrolyte therapy is highlighted.

PMID- 9515479
TI  - Management of the patient with sickle cell disease.
AB  - Sickle cell disease is a group of genetic disorders of hemoglobin synthesis, of
      which sickle cell anemia is the most severe. In the United States, sickle cell
      disease primarily affects persons of African-American and Hispanic origin. An
      estimated 50,000 Americans have the disease, and approximately 2.5 million
      persons carry the sickle cell trait. The primary pathophysiologic features are
      chronic hemolysis and vaso-occlusion. This disease is recurrent and
      unpredictable, causing considerable physiologic and psychologic stress. This
      article provides an overview of the disease and addresses the role of the
      infusion nurse in the care and support of the patient with sickle cell disease in
      the hospital and home setting.

PMID- 9515480
TI  - A comparison of flow rates between Baxter Continu-Flo and Baxter InterLink
      Continu-Flo.
AB  - Drip chamber size on intravenous administration sets varies. The practitioner may
      select a minidrip intravenous administration set to administer low flow rate IVs
      or medications. Baxter's InterLink Continu-Flo is available in minidrip size
      without restrictive tubing. The purpose of this study was to determine how much
      faster the nonrestrictive InterLink tubing would deliver i.v. fluid than would
      the Baxter Continu-Flo set with its minidrip chamber and restrictive tubing.

PMID- 9515481
TI  - Considerations in the use of lipid-based drug products.
AB  - The availability and use of intravenous lipid-based drug products is increasing.
      These products may have increased efficacy, decreased adverse effects, or both
      when compared with conventional formulations of the same drug. Lipid-based drug
      products have nutrition support implications when a substantial caloric dose is
      received during administration of the drug. They also may have unique toxicities
      and much greater costs than do traditional therapies. The rationale for the use
      of lipid-based drug products is presented, along with an overview of the proper
      use of current commercially available lipid-based amphotericin B, propofol,
      daunorubicin, and doxorubicin products.

PMID- 9515482
TI  - Antibiotic and anti-infective agent use and administration in homecare.
AB  - Homecare administration of intravenous antibiotics and anti-infectives is a
      rapidly growing service of the healthcare system. Knowledge of disease states
      that are amenable to homecare intravenous antibiotics includes those of long-term
      duration or deep-seated infections not suitable for oral therapy. Consideration
      of patient populations that are identified as appropriate for homecare
      intravenous antibiotic therapy includes the very young and old patients, pregnant
      patients, and patients with HIV. Awareness of a patient's medication history
      relating to allergic reactions allows guided monitoring before, during, and after
      intravenous antibiotic administration. Recognition of potential adverse drug
      reactions associated with each class of anti-infectives, as well as those related
      to the dose or infusion process, is another important part of safe and effective
      intravenous antibiotic administration.

PMID- 9515483
TI  - Intravenous nursing. Standards of practice. Intravenous Nurses Society.

PMID- 9515484
TI  - A New Year's vision statement: "what can be imagined, can be achieved!".

PMID- 9515485
TI  - Five easy steps to helping your low vision patients.

PMID- 9515486
TI  - New developments in the management of retinoblastoma.

PMID- 9515487
TI  - Choroidal detachment simulating choroidal melanoma.

PMID- 9515488
TI  - Potential air bag-related eye injuries require special ER attention.

PMID- 9515489
TI  - Self-assessment quiz. Valsalva purpura.

PMID- 9515491
TI  - Needed: a new set of immunizations.

PMID- 9515490
TI  - A guide to contact lens solutions.

PMID- 9515492
TI  - GAPS: an opportunity for nurse practitioners to promote the health of adolescents
      through clinical preventive services.
AB  - Today the leading causes of morbidity and mortality among adolescents originates
      in social and behavioral determinants. Thus much of adolescent death and
      disability can be attributed to preventable risk factors. In response, clinical
      preventive services have been developed by the American Medical Association to
      shift the focus of care to prevention. Guidelines for Adolescent Preventive
      Services recommendations address delivery of health services, health guidance,
      screening, and immunizations. Nurse practitioners are uniquely positioned to
      promote health and improve the quality of care delivered to adolescents. The
      purpose of this article is to describe the Guidelines for Adolescent Preventive
      Services model for clinical preventive services and the role of the nurse
      practitioner in implementation.

PMID- 9515493
TI  - Primary care for children with human immunodeficiency virus infection.
AB  - Pediatric human immunodeficiency virus (HIV) infection is now the seventh leading
      cause of death in U.S. children 1 to 14 years of age and the leading cause of
      death in children 2 to 5 years of age in many U.S. cities. The key to enhancing
      the quality and duration of life in HIV-infected children is to recognize and
      diagnose HIV infection as early as possible and to initiate prophylactic and
      antiretroviral therapies. Most of the medical treatment of these children can be
      conducted in a primary care setting if (a) primary care practitioners are
      informed of current treatment regimens and (b) adequate pediatric HIV
      consultation service is available. This article reviews the primary care of HIV
      infected children including early diagnosis, current treatment options, and the
      complex psychosocial issues associated with caring for these children.

PMID- 9515494
TI  - Teaching self-care to delinquent adolescents.
AB  - Adolescent delinquency is an ever-increasing societal concern. Certain health
      problems are concentrated in the delinquent population. Families of delinquent
      youths often fail to reinforce self-care. Therefore health care providers need to
      focus on ways to teach delinquent adolescents to care for themselves. This
      article reviews delinquency and characteristics of juvenile delinquents and their
      families. A model is presented to guide health care providers to assess
      delinquent adolescents' abilities to care for themselves and to teach them
      strategies for self-care.

PMID- 9515495
TI  - Persistent failure-to-thrive: a case study.
AB  - The inability to successfully feed a young infant or child is as worrisome to
      parents as it is to the health care provider. Early growth failures are likely to
      reflect difficulty with infant homeostasis and often respond to medical
      management of the physical problem that is temporarily interfering with the
      infant's ability to feed by mouth. In addition to medical management, however,
      treatment also necessitates investigation and management of behavioral problems
      that so universally accompany growth failure. This article presents a case study
      of a child who presented with poor growth and respiratory symptoms associated
      with nonregurgitant gastroesophageal reflux, a clinical entity that can be
      difficult to recognize. Although surgical management of this condition was
      successful, persistent failure-to-thrive continued and was seemingly recalcitrant
      to treatment. The use of cyproheptadine as an appetite stimulant to promote
      weight gain in this child is discussed with a review of the current literature
      regarding this pharmacologic approach to poor weight gain. A behavioral-based
      treatment plan is described as an alternate management method, avoiding the use
      of pharmacologic agents in general.

PMID- 9515496
TI  - An overview of developmentally supportive care of the premature infant.

PMID- 9515497
TI  - Trisomy 21 syndrome: is there anything new?

PMID- 9515498
TI  - Management of acne vulgaris.

PMID- 9515499
TI  - Presyncope in a female adolescent.

PMID- 9515500
TI  - Privacy and confidentiality of health information.

PMID- 9515502
TI  - A well-oiled machine.

PMID- 9515503
TI  - Removal of CRNA supervision requirement proposed.

PMID- 9515504
TI  - APNs make their mark in today's VA.

PMID- 9515505
TI  - The CNS links home and hospital.

PMID- 9515506
TI  - CRNAs--leaders in anesthesia care.

PMID- 9515507
TI  - Dispensing information instead of pills.

PMID- 9515508
TI  - Acute/critical care NPs emerge.

PMID- 9515509
TI  - Code seven: the birth of the septuplets.

PMID- 9515510
TI  - Fat and cholesterol.

PMID- 9515511
TI  - The myths of APRN/Physician collaboration. Interview by Catherine Campion.

PMID- 9515512
TI  - A revised report card for patient care.

PMID- 9515513
TI  - Doctorally-prepared nurses: different practice settings, different views.
AB  - Nurse researchers in academic and clinical settings have the ultimate goal of
      improving nursing care while balancing the demands of education, their
      institution, research, and nursing service. The setting shapes the focus of
      research, the choice of research models, and the parameters of the position. The
      setting also influences available resources and the services rendered to the
      institution and the community. The functions of doctorally-prepared nurses in
      academic and clinical settings are compared. A better understanding of the
      functions of nurses in each setting could lead to better informed employment
      choices and improved collaborative efforts.

PMID- 9515514
TI  - The case for national licensure.

PMID- 9515515
TI  - Tips for success when returning to school.
AB  - Two nurse faculty members who were previously nontraditional students discuss a
      concrete strategy for the nurse who is returning to school. Tips and suggestions
      on how to deal with the educational system, how to be a student again, and how to
      balance work, home, and school are included.

PMID- 9515516
TI  - Toward an ethics of dementia.

PMID- 9515517
TI  - Health care needs in a nontraditional university setting.
AB  - This paper describes early planning stages of a nurse-managed clinic to offer
      primary health care services in a nontraditional university setting. A community
      needs assessment was conducted with quantitative and qualitative findings
      reported. This unique setting triggered a number of considerations in planning
      for services. Recommendations for health services and resources for the
      university community are discussed.

PMID- 9515518
TI  - Psychiatric nursing interventions in managed care: is there time for caring?
AB  - Today's managed care affects how health care is provided: Caregivers focus on the
      needs of patients while struggling to fulfill the demands of the institutions for
      which they work. Presented here are some underlying concepts of patient care as
      well as some suggestions for further research which include the collaboration and
      consultation of nursing faculty with service. This article which is intended as a
      primer for the transition of novice psychiatric nurses to experts considers the
      effects of managed care.

PMID- 9515519
TI  - Ethics in research: nursing perspectives.
AB  - Research is an important priority in nursing. Nurses attempting to carry out
      studies in health care today, however, face greater complexity, financial
      pressures and ethical dilemmas than in the past. To meet these challenges, nurses
      need a solid understanding of research standards underpinned by ethical
      principles. In this article, the author discusses recent controversies in
      research including informed consent and interpretation of research results, as
      well as an action plan for greater attention to ethics in nursing research.

PMID- 9515520
TI  - The Breast Reconstruction Advocacy Project: one woman can make a difference.

PMID- 9515521
TI  - Duration of antimicrobial prophylaxis in vascular surgery.
AB  - BACKGROUND: This randomized clinical trial compares the incidence of wound
      infection after vascular surgery in patients who received prophylaxis using the
      same antibiotic as either a single-dose or a multiple-dose regimen (until the
      lines/drain tubes were removed, but not for more than 5 days). METHODS: Each of
      the 302 patients who entered the study received ticarcillin 3.0 g/clavulanate 0.1
      g (Timentin) intravenously immediately after the induction of anesthesia.
      Patients randomized to the multiple-dose group received an average of 14.3 doses
      (range 9 to 20). RESULTS: The incidence of wound infections was 18% (28 of 153)
      for patients in the single-dose group and 10% (15 of 149) for patients in the
      multiple-dose group (P = 0.04; relative risk estimate = 2.00, 95% confidence
      interval = -1.02 to 3.92). CONCLUSIONS: A multiple-dose antibiotic regimen,
      rather than single-dose therapy, provides optimal prophylaxis against wound
      infection for patients undergoing vascular surgery.

PMID- 9515522
TI  - Management of necrotizing pancreatitis by repeated operative necrosectomy using a
      zipper technique.
AB  - METHODS: From 1983 to 1995, 72 patients with necrotizing pancreatitis were
      treated with a general approach involving planned reoperative necrosectomies and
      interval abdominal wound closure using a zipper. RESULTS: Hospital mortality was
      25%. Multiple organ failure without sepsis caused early mortality in 3 of 4
      patients and sepsis caused late mortality in 11 of the remaining 14. The mean
      number of reoperative necrosectomies/debridements was 2 (0 to 7). Fistulae
      developed in 25 patients (35%); 64% were treated conservatively. Recurrent
      intraabdominal abscesses developed in 9 patients (13%) but were drained
      percutaneously in 5. Hemorrhage required intervention in 13 patients (18%).
      Prognostic factors included APACHE-II score on admission < 13 (P = 0.005),
      absence of postoperative hemorrhage (P = 0.01), and peripancreatic tissue
      necrosis alone (P < 0.05). CONCLUSIONS: The zipper approach effectively maximizes
      the necrosectomy and decreases the incidence of recurrent intraabdominal
      infection requiring reoperation. APACHE-II score > or = 13, extensive parenchymal
      necrosis, and postoperative hemorrhage signify worse outcome.

PMID- 9515523
TI  - Intraoperative ultrasound does not improve detection of liver metastases in
      resectable pancreatic cancer.
AB  - BACKGROUND: In colorectal cancer, intraoperative ultrasound (IOUS) is superior to
      other imaging studies in characterizing hepatic metastases. The value of IOUS in
      detecting liver metastases from pancreatic cancer has not been evaluated
      previously. METHODS: Between 1990 and 1995, IOUS was prospectively employed to
      evaluate the liver for metastases in 32 patients with resectable pancreatic
      adenocarcinoma. Preoperatively, all patients had computed tomography (CT) and 22
      patients had CT portography. RESULTS: At exploration, 5 of the 32 patients (15%)
      had extrapancreatic disease, 3 (9%) with liver implants. IOUS did not identify
      any additional hepatic metastases. Four preoperative studies were suspicious for
      metastatic disease in the liver. In these 4 patients, no hepatic metastases were
      identified by exploration or intraoperative ultrasound. CONCLUSIONS: We no longer
      routinely perform hepatic IOUS when evaluating patients with pancreatic
      adenocarcinoma for pancreaticoduodenectomy. When a preoperative study indicates
      possible hepatic involvement, IOUS can confirm the presence or absence of liver
      metastases.

PMID- 9515524
TI  - Is splenectomy more dangerous for massive spleens?
AB  - BACKGROUND: Reports vary about whether risks are greater for removal of massive
      (> or = 1500 g) spleens than for smaller (< 1500 g) spleens. We sought to
      determine the hazards of splenectomy. METHODS: We reviewed 223 consecutive adults
      with elective splenectomies for hematologic diseases. Morbidity and mortality
      rates were combined with published data to create a meta-analysis. RESULTS:
      Patients with massive spleens are more likely to have postoperative complications
      (relative risk [RR] 2.1, 95% confidence interval [CI] 1.3 to 3.4; P = 0.003) and
      death (RR 4.7, 95% CI, 1.5 to 15.1; P = 0.01). However, when the investigation is
      restricted to comparable diagnoses, patients with massive spleens do not differ
      from those with smaller spleens regarding complications (RR 1.4, 95% CI, 0.8 to
      2.7; P = 0.3) or mortality (RR 2.1, 95% CI, 0.5 to 9.7; P = 0.4). These
      observations are confirmed by metaanalysis. Furthermore, multivariate analysis
      indicts age as a critical risk of complications and death. CONCLUSIONS: Increased
      age and underlying illness are the predominant factors associated with morbidity
      and mortality following splenectomy for hematologic disease. Adjusting for age
      and diagnosis, spleen size is not a hazard.

PMID- 9515525
TI  - Percutaneous dilatation of biliary strictures through the afferent limb of a
      modified Roux-en-Y choledochojejunostomy or hepaticojejunostomy.
AB  - BACKGROUND: This report is a 13-year prospective evaluation of percutaneous
      balloon dilatation of benign biliary strictures through the subcutaneous or
      subfascially positioned afferent limb of a choledocho or hepaticojejunostomy in
      30 patients. DATA SOURCE: Twenty-seven strictures developed after a common duct
      injury sustained at the time of cholecystectomy, two after hepatectomy
      reconstruction for trauma and one following a gastrectomy. Twelve injuries (40%)
      were recognized at operation. Of the 18 patients where the injury was
      unrecognized at the time of operation, 8 had not been reoperated at the time of
      referral, 7 had late repairs by the referring physician, and 3 had late repairs
      at our institution. The follow-up is 1 to 13 years. RESULTS: There has been 1
      late death and 6 patients are lost alive. The jejunal-limb was accessed 50 times
      with two minor and no major complications. There have been two parajejunal hernia
      repairs, but there have not been any reoperations for recurrent biliary
      strictures. CONCLUSIONS: Benign biliary strictures can be effectively managed by
      repeat balloon dilatations thru the afferent limb of a choledocho or
      hepaticojejunostomy, thus eliminating the need for repeat surgical interventions.

PMID- 9515526
TI  - Surgical indications for small polypoid lesions of the gallbladder.
AB  - BACKGROUND: To determine which polyps of the gallbladder should be operated upon,
      we investigated the size and number of polyps in resected gallbladders, and
      studied changes in gallbladder polyps using ultrasonography (US). METHODS: We
      studied 74 resected gallbladders with small polypoid lesions less than 20 mm in
      diameter, and 60 patients with gallbladder polyps by US. The polyps in resected
      gallbladders were classified into four groups histologically, and clinical
      features, maximum diameter, and number of lesions were compared among the groups.
      In the followed-up cases with gallbladder polyps, the size and number of polyps
      were examined by US, and changes during the observation period were studied.
      RESULTS: The mean diameter of adenoma was 6.00 +/- 3.39 mm (mean +/- SD) and that
      of cancer 10.8 +/- 4.16 mm; 97% of cholesterol polyps were less than 10 mm in
      diameter (3.66 +/- 2.68 mm). Neoplastic polyps tended to be single (adenoma, n =
      1.40 +/- 0.89; cancer, n = 1.16 +/- 0.40), whereas half of the cholesterol polyps
      were multiple (n = 3.09 +/- 3.31). However, when there were fewer than 3 lesions,
      the incidence of neoplasm was 37% among polyps 5 to 10 mm in diameter. A low
      incidence (6%) of neoplasm was also observed among polyps less than 5 mm in
      diameter. CONCLUSIONS: These data indicate that an aggressive surgical approach
      for small gallbladder polyps is warranted when there are fewer than 3 polyps,
      regardless of their size.

PMID- 9515527
TI  - Long-term results after curative resection for carcinoma of the gallbladder.
      French University Association for Surgical Research.
AB  - BACKGROUND: The surgical management of gallbladder carcinoma is controversial,
      especially as regards the indications for radical resection. The aim of this
      study was to evaluate the results of surgical treatment for gallbladder carcinoma
      with special reference to the extent of its histological spread. METHODS: Eighty
      six patients from 25 French centers underwent resection for cure and were
      included in this study. They comprised 65 women and 21 men (mean age 65 +/- 21
      years). Resection included radical resection in 21 patients (partial hepatectomy,
      regional lymphadenectomy, and common bile duct resection) and simple
      cholecystectomy in 65. RESULTS: There were 3 postoperative deaths (3.5%). The
      mean follow-up period was 25 +/- 24 months. The overall 5-year actuarial survival
      rate was 26%. The 5-year actuarial survival rate was 27% for patients who had
      radical resection. Eight patients with nodal metastasis had a 5-year survival
      rate of 0%, but the rate for 13 patients without such metastasis was 43% (P
      <0.05). For patients undergoing simple cholecystectomy, the 5-year actuarial
      survival rate was 44% for stage I disease, 22% for stage II, and 0% for stage III
      (P <0.05). CONCLUSIONS: In patients with stage I gallbladder carcinoma, outcome
      is good after cholecystectomy only. In stages II to IV, radical resection should
      only be considered in the absence of regional lymph node metastasis.

PMID- 9515528
TI  - Extended surgical resection in T4 gastric cancer.
AB  - BACKGROUND: Some physicians still consider invasion of adjacent organs by the
      carcinoma of stomach as a sign of incurable disease. METHODS: This retrospective
      study has been done with particular reference to 353 T4 gastric cancer patients
      who underwent combined gastrectomies with adjacent organs. RESULTS: Subtotal
      gastrectomy was performed in 237 (67.1%) patients and total gastrectomy was
      performed in 116 (32.9%) patients. Organs most commonly resected with the stomach
      were the transverse colon in 159 (45%) cases, the tail of pancreas and spleen in
      150 (42.5%), the left lobe of liver in 101 (28.5%), and the head of pancreas in
      37 (10.5%) patients. A total of 110 postoperative complications occurred in this
      subset of patients corresponding to a complication rate of 31.2%. A total of 48
      postoperative deaths occurred in this subset of patients corresponding to a
      mortality rate of 13.6%. The 5-year survival rate for all patients who underwent
      combined gastrectomy with adjacent organs was 25%. Of the node-negative T4
      gastric cancer resections, 37% survived 5 years whereas the T4 node-positive
      resections have only a 15% 5-year survival. CONCLUSIONS: Patients who present
      with T4 gastric cancer (about 20% of the patient population) will benefit from
      aggressive en bloc surgical resection and should not be considered unresectable.

PMID- 9515529
TI  - Treatment of large and locally advanced breast cancers using neoadjuvant
      chemotherapy.
AB  - BACKGROUND: Neoadjuvant (primary) chemotherapy is being used increasingly in the
      treatment of patients with large and locally advanced breast cancer with the aim
      of reducing the size of the primary tumor and eliminating micrometastatic
      disease. Response rates to, compliance with, and survival of patients following
      neoadjuvant chemotherapy have been variable. We report the results of a
      consecutive series of 77 patients with breast cancer who received neoadjuvant
      chemotherapy. METHODS: Seventy-seven patients with locally advanced breast
      cancers were treated with multimodality therapy comprising up to six cycles of
      chemotherapy (cyclophosphamide, vincristine, doxorubicin, and prednisolone),
      radiotherapy, and then surgery. The median follow-up was 54 months. Clinical
      response rates to therapy and overall survival have been documented. In addition,
      prognostic factors for survival were identified using the Cox proportional
      hazards model. RESULTS: The overall objective response rate of the primary tumor
      to chemotherapy alone was 87% (25% complete and 62% partial responses, UICC
      criteria). Following radiotherapy the response rate was 90% (52% complete and 38%
      partial responses). The overall 5-year survival for all patients was 0.48.
      However, the probability of survival at 5 years was 0.74 in those with a complete
      response, and 0.36 if there was a partial clinical response, but no patients who
      had either stasis of disease or progression survived for 5 years. Independent
      predictors of better survival that were identified were a complete
      histopathological response after chemotherapy and radiotherapy, a complete
      clinical response to chemotherapy, and five or six cycles of chemotherapy versus
      four or less. CONCLUSIONS: Neoadjuvant chemotherapy in patients with large and
      locally advanced breast cancers can result in satisfactory local control and
      overall survival rates, especially in patients with a complete clinical or
      histopathological response after treatment.

PMID- 9515530
TI  - Evaluation of ultrasound-guided fine-needle aspiration biopsy for thyroid
      nodules.
AB  - BACKGROUND: We retrospectively studied whether ultrasound-guided fine-needle
      aspiration biopsy (US-FNAB) showed improved sensitivity in patients with palpable
      thyroid nodules. METHODS: A total of 70 patients (72 lesions) with thyroid
      nodules underwent US-FNAB and 94 patients (94 lesions) underwent FNAB guided by
      manual palpation (standard FNAB). The diagnoses obtained by US-FNAB were compared
      with the surgical findings. RESULTS: The sensitivity of US-FNAB for palpable
      thyroid nodules was 62% the specificity was 74% the accuracy was 68% the positive
      predictive value was 100%, the negative predictive value was 70% and the
      inadequate biopsy rate was 17%. In contrast, the sensitivity of standard FNAB was
      45%, the specificity was 51%, the accuracy was 48% the positive predictive value
      was 96, the negative predictive value was 55, and the inadequate biopsy rate was
      30%. The accuracy of US-FNAB was significantly higher than that of standard FNAB.
      For tumors < or = 2 cm in diameter, the sensitivity and accuracy of US-FNAB were
      both significantly higher than those of standard FNAB. CONCLUSION: These findings
      suggest that US-FNAB can improve the preoperative diagnosis of thyroid cancer,
      especially in patients with tumors < or = 2 cm in diameter.

PMID- 9515531
TI  - An experimental study of the effect of aprotinin on intestinal adhesion
      formation.
AB  - BACKGROUND: Depression of fibrinolysis is known to be a major mechanism for
      postoperative adhesion formation. Because aprotinin inhibits fibrinolysis it may
      lead to an increase in adhesion formation whereas its anti-inflammatory effects
      may lead to a decrease in adhesion formation. Our aim is to clarify conflicting
      results in previous literature. METHODS: Basal levels of intestinal
      hydroxyproline (OHP) content and local fibrinolytic activity (LFA) were
      determined using naive groups. In the experiment groups, adhesions were created
      by scraping and creating a transient ischemia of a segment of terminal ileum.
      Group I and II rats were injected subcutaneous (s.c.) normal saline (NS) for 3
      days and single dose intraperitoneal (i.p.) NS, respectively. Group III and IV
      rats were injected s.c. aprotinin for 3 days and single dose i.p. aprotinin,
      respectively. Group V rats were injected intramuscular methylprednisolone (MP)
      for 3 days. LFA and OHP levels were determined on the second and fifth
      postoperative days. The severity of adhesion formation was graded on the fifth
      day. RESULTS: Aprotinin decreased both the severity of adhesions and OHP levels
      whereas MP decreased only the severity of adhesions. There was an early
      depression of LFA at the second day in both NS and MP groups increasing to basal
      levels at the fifth day. OHP levels showed significant correlation with adhesion
      severity. CONCLUSION: Results showed that aprotinin decreased intra-abdominal
      adhesion formation probably by preventing early depression of LFA.

PMID- 9515532
TI  - Effects of a urinary trypsin inhibitor on acute circulatory insufficiency after
      surgical operation.
AB  - OBJECTIVE: To assess the effectiveness of an urinary trypsin inhibitor (UTI) on a
      surgical stress, particularly the influences on cytokines and diuretic hormones.
      SUBJECTS AND METHODS: Sixteen patients with carcinoma of the digestive system and
      predicted to suffer from circulatory insufficiency were enrolled. Selection of
      group was divided alternatively. UTI was administered for 5 consecutive days, at
      a dose of 300,000 units per day. Urine and blood specimens were collected before,
      immediately after, and 1, 3, and 5 days after surgery. Interleukin 8 (IL-8),
      polymorphonuclear leukocyte elastase (PMNE), vasopressin (ADH), atrial
      natriuretic peptide (ANP), angiotensin II (AT-II), and endothelin 1 (ET-1) in the
      blood, and N-acetyl-D-glucosaminidase (NAG) in the urine, were determined.
      RESULTS: A UTI group was 9 patients, and a control group was 7 patients. The
      operation time was significantly longer in the UTI group than in the control
      group. In the UTI group, the elevation of IL-8, PMNE/WBC, ADH, urinary NAG, and
      BUN were significantly inhibited. AT-II and ET-1, in the UTI group, tended to be
      suppressed, and ANP showed the similar changes in the two groups. CONCLUSION: UTI
      is considered effective in the prevention of excessive reaction against major
      surgery.

PMID- 9515533
TI  - Differential effect of cyclooxygenase metabolites on proinflammatory cytokine
      release by Kupffer cells after liver ischemia and reperfusion.
AB  - BACKGROUND: Liver ischemia and reperfusion (I/R) induce Kupffer cell (KC)
      activation with increased release of proinflammatory cytokines. Prostaglandins
      are potent counterregulatory mediators to control the production of cytokines by
      macrophages. METHODS: To study the role of cyclooxygenase metabolites for the
      release of proinflammatory cytokines by KC in liver I/R, Sprague-Dawley rats were
      subjected to 20-minute global hepatic ischemia and 60 minutes of reperfusion.
      Sham-operated animals were used as controls. Kinetics of spontaneous and
      lipopolysaccharide (LPS)-induced release of proinflammatory cytokines and
      prostaglandin E2 (PGE2) by KC were assessed both in the presence and absence of
      the cyclooxygenase inhibitor ibuprofen. RESULTS: Early after liver I/R (4, 16
      hours) the spontaneous secretion of TNF-alpha (+1,058%), IL-1alpha (+152%), and
      IL-6 (+161%) by KC was increased (P <0.05), while PGE2 release in the I/R group
      was reduced by 51% (P <0.05) in comparison with the sham-operated group.
      Increased release of PGE2 in the later period (32 hours) after I/R was associated
      with decreased TNF-alpha release by KC. Inhibition of PGE2 production by
      ibuprofen induced a prolonged and enhanced production of TNF-alpha, while the
      release of IL-1alpha and IL-6 was not affected. CONCLUSIONS: Liver I/R leads to a
      temporary suppression of PGE2 release by KC, while the release of TNF-alpha is
      increased. Thus, during early reperfusion, excessive secretion of TNF-alpha by KC
      may be the result of the absent negative feedback control of cyclooxygenase
      metabolites.

PMID- 9515534
TI  - The utility of the Hartmann procedure.
AB  - BACKGROUND: In 1923 the French surgeon Henri Hartmann described an operation for
      rectosigmoid cancer as an alternative to abdomino-perineal resection for high
      risk patients. In the subsequent years, the indications for performing the
      Hartmann procedure have broadened to include complicated diverticulitis, ischemic
      bowel, iatrogenic perforations, volvulus, and colitis. METHODS: We have
      retrospectively reviewed our experience in 185 patients who underwent the
      Hartmann procedure from January 1981 to December 1995. Charts were reviewed for
      indications, morbidity, and mortality and to determine the outcome of patients
      who underwent the Hartmann procedure. RESULTS: The main indications for
      performing the Hartmann procedure were complicated diverticulitis (including
      perforation, obstruction, and abscesses) in 108 patients, rectosigmoid cancer in
      31 patients, and other indications in 46 patients. There were a total of 27
      deaths for an in-hospital mortality of 14%. All complications occurred at a rate
      of less than 9%. Of the 158 surviving patients, 90 (57%) eventually underwent the
      second stage of the operation to restore bowel continuity. The average length of
      time between initial resection and reanastomosis was 149 days. There were no
      deaths associated with the second stage of the procedure and complications
      occurred at a rate less than 4%. CONCLUSIONS: This is the largest reviewed series
      of the Hartmann procedure. Mortality is lower than in other reported series, and
      morbidity is low. Our data demonstrate that the second stage of the procedure, in
      properly selected individuals, is a procedure that can be performed with minimal
      morbidity and no mortality. This is different from other published reports. We
      conclude that the Hartmann procedure is a safe and efficacious option for the
      surgeon confronted with the complex pathology of the rectosigmoid area, with
      acceptable morbidity and mortality.

PMID- 9515535
TI  - Use of a Foley catheter in the removal of a substernal goiter.
AB  - Substernal goiters present a technical challenge to the surgeon. Most substernal
      goiters may be removed through a cervical incision; however, a median sternotomy
      may be required in 1% to 2% of patients. To avoid a median sternotomy, many
      techniques have been described in the literature to facilitate extraction.
      Special spoons and clamps have been described, and techniques, such as
      morcellation, the drawer technique, and piecemeal extraction, have been
      popularized. We describe a method whereby a Foley catheter is used to deliver a
      large substernal goiter through a cervical incision. It consists of steady
      traction on the inflated balloon of a Foley catheter placed beyond the substernal
      component of the goiter. This method has been used successfully and safely on 2
      patients and may obviate the need for a sternotomy.

PMID- 9515536
TI  - Anoplasty for the treatment of anal stenosis.
AB  - BACKGROUND: Cicatricial stenosis of the anal canal is a disabling complication of
      anal surgery. Many different surgical techniques have been described for the
      management of this disorder. METHODS: In this study we report 42 patients with
      severe anal stricture treated with anoplasty. Twenty-nine of these patients
      underwent a Y-V anoplasty while 13 had a diamond flap anoplasty. All patients
      were seen 4 weeks, 6 months, and 2 years after surgery. RESULTS: Three patients
      who had undergone Y-V anoplasty experienced, as a minor early operative
      complication, a suture dehiscence and 1 patient had an ischemic contracture of
      the leading edge of the flap. Two patients had urinary infections. None of these
      complications needed further surgical intervention and were all managed with
      local and medical therapy. At 2 years follow-up 93% of patients had been
      successfully treated while the remaining 7% had improved. Fifteen percent of
      patients who had undergone Y-V anoplasty complained of postoperative
      complications, and all patients with incomplete results had been treated with an
      Y-V anoplasty. CONCLUSIONS: Based on our cohort of patients we believe that both
      techniques are satisfactory in treating anal stricture but diamond flap anoplasty
      seems more reliable because of the reduced tension at the suture line and the
      better blood supply to the flap.

PMID- 9515537
TI  - Is radical hepatic surgery safe?
AB  - BACKGROUND: A prospective review of 200 consecutive liver resections performed
      for benign and malignant disease, between 1989 and 1995 at the Hammersmith
      Hospital, was undertaken to evaluate the safety of radical hepatic resection.
      METHODS: The indications for operation were: hepatocellular carcinoma (n = 39),
      cholangiocarcinoma (n = 21), gall bladder carcinoma (n = 8), colorectal
      secondaries (n = 75), noncolorectal secondaries (n = 35), and benign disease (n =
      26). Twenty patients were cirrhotic and 36 were jaundiced. Major resections were
      performed in 74% of cases and included 63 extended hepatectomies, 17 repeated
      resections for recurrent colorectal metastases, and 17 resections combined with
      vascular reconstruction. Total vascular exclusion of the liver was used in the
      majority of cases. RESULTS: The overall mortality rate was 5%. Thirty-day
      mortality was 2.5%. Sepsis and not hemorrhage was the most common cause of death.
      There were 101 complications that occurred in 37% of the patients. The main
      complications were subphrenic abscess and biliary leak. The extent of liver
      resection (major versus minor) significantly increased the risk of morbidity (46%
      versus 16%). Blood loss greater than 100 mL increased the risk of morbidity from
      12% to 25%. CONCLUSIONS: Major hepatic resection can be achieved with acceptable
      mortality but high morbidity rates.

PMID- 9515538
TI  - Clinical presentation and management of iatrogenic colon perforations.

PMID- 9515539
TI  - Palisade dorsoventral lavage for neglected peritonitis.

PMID- 9515540
TI  - Transparietal feeding-jejunostomy catheter.

PMID- 9515541
TI  - Standardization of diuresis renography techniques.

PMID- 9515542
TI  - Future developments in nuclear medicine instrumentation: a review.
AB  - This review article forecasts developments in nuclear medicine instrumentation
      which are on the horizon. Special attention is paid to the physical properties of
      detectors and multiple-processor parallel processing systems needed for fast and
      high-quality imaging in emission tomography. Advances in detector technology will
      improve imaging resolution below 5 mm and will increase sensitivity and
      quantitative accuracy. In addition, high count rate list-mode acquisition enables
      'true' four-dimensional data-sets. A sandwich-like construction of two different
      crystals allows the simultaneous use of conventional tracers and positron tracers
      (multiple emission tomography, MET). Transmission-based attenuation and scatter
      compensation with fast iterative reconstruction methods will further improve
      image quality. The clinical and scientific importance of improved images and the
      limits on advances in instrumentation are also reviewed.

PMID- 9515543
TI  - SPET and three-phase planar bone scintigraphy in adult patients with chronic low
      back pain.
AB  - Among adults, low back pain (LBP) persisting for more than 3 months is a common
      complaint. A variety of imaging modalities including bone scintigraphy have been
      recommended as appropriate for the investigation of chronic LBP, even when there
      is no reason to suspect that the pain is due to tumour, infection or inflammatory
      arthritis. In this chronic LBP population, the diagnostic benefit of bone SPET,
      together with planar flow study, blood pool and delayed three-phase imaging, was
      assessed, Altogether, 2108 consecutive adult patients were entered into the
      chronic LBP bone scintigraphy database. Retrospective exclusion of patients with
      a history of tumour, infection or inflammatory arthritis reduced the population
      to 1390, of whom 916 underwent a lumbosacral spine flow study and blood pool
      imaging in addition to planar and SPET bone scintigraphy. The diagnostic benefit
      of these imaging studies was tabulated and compared. In addition, a retrospective
      chart review of the patients with renal and other soft tissue abnormalities
      identified by a flow study and blood pool imaging was undertaken with a view to
      documenting any changes in treatment planning over the 6 months following the
      nuclear medicine studies. Of the lumbosacral spine abnormalities, 44.1% were seen
      equally well on planar and SPET images, 24.0% better on SPET, 31.4% only seen on
      SPET, and 0.4% only seen on planar imaging. The distribution of abnormalities
      identified on SPET images in the lumbar spine was divided between vertebral
      bodies (36.1%), lamina or pedicles (which included frequent sites of increased
      uptake in the articular facets and pars interarticularis) (53.8%), spinous
      processes (8.7%) and transverse processes (1.3%). For the flow study and blood
      pool imaging, there was a 16.7% rate of positive studies. However, there were no
      documented changes in treatment planning because of these positive findings. In
      conclusion, when used to examine adult patients with chronic LBP, SPET detects
      significantly more scintigraphic abnormalities than planar imaging. The addition
      of a flow study and blood pool imaging as part of these LBP examinations results
      in a significant benefit. However, the clinical utility of such flow study and
      blood pool imaging studies cannot be confirmed.

PMID- 9515544
TI  - Cerebral functional-morphological match or mismatch in cerebrovascular disease: a
      comparison of flow-volume SPET, CT findings and Doppler sonography.
AB  - Cerebral ischaemia (thromboembolic, haemodynamic) is usually classified according
      to morphological criteria, but intracerebral rheological aspects often remain
      underestimated, even though prognosis may depend on areas of reduced perfusion or
      perfusion reserve around a morphological defect. The aim of this study was to
      investigate regional haemodynamics in patients with cerebrovascular ischaemia by
      comparing the size of morphological defects (MD) and perfusion deficits (PD).
      Ninety patients with cerebrovascular disease were investigated and the size of
      morphological defects on computed tomography (CT) was compared to the size of
      perfusion deficits or the extent of exhausted cerebral perfusion reserve (CPR) on
      a combined flow-volume single photon emission tomographic (SPET) study. Carotid
      arteries were examined by Doppler ultrasonography. Defect/deficit size ratios of
      MD, PD and CPR were classified as: (1) CT/SPET mismatch: A (no MD or PD, reduced
      CPR), B (PD > MD); or (2) CT/SPET match: C (PD = MD). A CT/SPET mismatch was
      found in 79% of patients with a haemodynamic pattern and in 67% of transient
      ischaemic attack/reversible ischaemic neurological deficit patients who showed no
      MD. A mismatch was also found in 21% of patients with thromboembolic infarction.
      A match was found in 79% of the thromboembolic and in 16% of the haemodynamic
      infarctions. High grade (> 80%) stenosis of the internal carotid arteries was
      found in 81% of the mismatch cases, but in only 57% of the match cases. In
      conclusion, haemodynamic infarctions show a predominance of
      functional/morphological mismatch, a match being predominant in thromboembolic
      infarctions. Doppler failed to indicate disturbed intracerebral perfusion in
      nearly one-fifth of haemodynamically compromised patients. In addition to CT and
      Doppler, flow-volume SPET enables an assessment of intracerebral haemodynamics
      which might be relevant for prognosis and therapy.

PMID- 9515545
TI  - Subtraction ictal SPET co-registered to MRI in partial epilepsy: description and
      technical validation of the method with phantom and patient studies.
AB  - Computer-aided subtraction of the co-registered and normalized interictal from
      the ictal single photon emission tomography (SPET) scan, followed by co
      registration to the magnetic resonance image, may improve the utility of ictal
      SPET in the localization of partial epilepsy. This paper describes and
      technically validates our method. The SPET to SPET co-registration was tested
      using six sequential 99Tc(m) brain phantom SPET images of different known
      positions (15 matches). The registration error was determined by multiplying the
      calculated match transformation matrix by the inverse of the known transformation
      matrix. The 'worst case' co-registration error was less that one voxel diameter
      in all cases (median 3.2 mm, range 1.2-4.8 mm). For interictal to ictal SPET
      registrations in 10 consecutive intractable partial epilepsy patients, a similar
      root mean square distance (RMSD) between corresponding points on the matched
      scans was found as for the phantom studies (median 2.2 vs 2.6 mm). The
      appropriateness of our normalization was studied by comparing the pixel intensity
      distributions between the matched scans, and by analysing the subtraction pixel
      intensity distribution. The pixel intensity distribution for both the normalized
      phantom, and paired normalized patient studies, were closely matched to each
      other except for the extreme values, which in clinical situations likely
      represent regions of ictal activation or depression. The subtraction image
      intensity distributions were symmetrically centred on zero for all values up to
      at least within the 5th to 95th centile range, confirming good normalization for
      the 'non-activated' pixels. Also, a linear relationship was demonstrated between
      the measured pixel intensity on the phantom scans and the true changes in 99Tc(m)
      activity based on its decay constant. The results of this study demonstrate that
      our method produces accurate SPET to SPET co-registration, and appropriate SPET
      normalization, thereby allowing a valid ictal subtraction image to be derived.

PMID- 9515546
TI  - Comparison between 201Tl-chloride and 99Tc(m)-sestamibi SPET brain imaging for
      differentiating intracranial lymphoma from non-malignant lesions in AIDS
      patients.
AB  - The aim of this study was to compare 201Tl-chloride and 99Tc(m)-sestamibi (MIBI)
      SPET brain imaging for differentiating brain lymphoma from other intracranial
      lesions in AIDS patients. Both studies were performed on the same day in 17 AIDS
      patients with intracranial enhancing lesions on either CT or MRI. Eleven patients
      underwent brain biopsy and six patients were followed clinically. We calculated
      the radiopharmaceutical uptake ratio of the lesion to that on the contralateral
      side with the guidance of CT or MRI findings. Ratios of 1.5 or more were
      considered to represent malignant lesions and ratios < 1.5 were considered to
      represent benign lesions. Biopsy revealed four cases of lymphoma, four cases of
      toxoplasmosis and two cases of progressive multi-focal leukoencephalopathy; one
      biopsy yielded necrosis. Both the MIBI and 201Tl studies yielded no false
      negative cases of lymphoma (sensitivity 100%). Of the 13 non-lymphoma cases, the
      201Tl studies showed seven true-negative cases (specificity 54%) and the MIBI
      studies showed nine true-negative cases (specificity 69%). The biopsies of the
      false-positive cases (toxoplasmosis) showed a pattern of healing after medical
      treatment. We conclude that MIBI is more helpful than 201Tl because of higher
      specificity and equal sensitivity. The medical treatment of toxoplasmosis is a
      cause of false-positive 201Tl and MIBI studies.

PMID- 9515547
TI  - Limited value of scintimammography and contrast-enhanced MRI in the evaluation of
      microcalcification detected by mammography.
AB  - The aim of this study was to evaluate whether scintimammography using 99Tc(m)
      sestamibi or contrast-enhanced magnetic resonance imaging (MRI) can improve the
      specificity of mammography for the differentiation of benign and malignant breast
      microcalcification. From 156 consecutive patients studied with SMM, 44 patients
      with microcalcification on mammograms were selected for this study. Forty
      patients in this group also had contrast-enhanced MRI of the breast. The
      intensity and patterns of sestamibi uptake for scintimammography and contrast
      enhancement for MRI were visually determined and graded on a 5-point scale for
      malignancy. The results of both techniques were compared and correlated with
      final histopathologic diagnoses. The sensitivity and specificity of
      scintimammography were 63% and 85% respectively, if only those cases classified
      as probable or definite malignancy were considered positive. If indeterminate
      findings were also considered positive, the sensitivity and specificity of
      scintimammography were 79% and 80% respectively. Using the latter classification
      for MRI revealed a comparable sensitivity of 82% but a markedly lower specificity
      of 56%. Excluding indeterminate findings from the group of positive MRI diagnoses
      resulted in a specificity of 94% and a sensitivity of 64%. In conclusion,
      scintimammography of the breast had a comparable sensitivity but a higher
      specificity than MRI. The sensitivity of both techniques, however, is probably
      too low for routine use in the evaluation of microcalcification detected by
      mammography.

PMID- 9515548
TI  - In vitro effect of contrast agents during immunoradiometric assay for tumour
      associated antigens.
AB  - The aim of this study was to investigate if contrast agents interfere with the
      performance of an immunoradiometric assay (IRMA) in vitro for serum tumour
      associated antigen. Each of five carcinoembryonic antigen (CEA)-positive sera, CA
      130-positive sera and tissue polypeptide antigen (TPA)-positive sera was mixed
      with six contrast agents: Ioversol 350, Iopamidol 370, Iomeprol 300, Iomeprol
      400, Iohexol 300 and Gadopenteic acid in 50:50, 50:20, 50:5.0, 50:1.0, 50:0.5 and
      50:0.1 microl proportions. Following IRMA, the interference of binding rates in
      each mixture was calculated, and the serum concentrations of CEA, CA-130 and TPA
      were estimated and compared with the originals. All contrast agents used were
      able to inhibit the binding rate with IRMA and the inhibition rates were in
      proportion to the amount of contrast agent. The detection of serum concentrations
      of CEA, CA-130 and TPA was significantly inhibited in the mixtures with more than
      5.0 microl of contrast agent in all cases. Apart from Iomeprol 400, there was no
      significant inhibition of detection at the lowest concentrations of contrast
      agents. Iomeprol 400 was the strongest inhibitor and Gadopenteic acid the weakest
      inhibitor for each IRMA of the contrast agents employed. In conclusion, our
      results demonstrate that contrast agents may reduce the immunoreaction of
      antibody and antigen and lead to in vitro inhibition during immunoassays. It
      would be unwise to perform any plasma/serum immunoassay on a sample collected
      within 24 h of the administration of contrast agent considering the
      pharmacokinetics.

PMID- 9515549
TI  - The value of the chest radiograph in reporting aerosol ventilation-perfusion
      scans.
AB  - It has become accepted practice to have a chest radiograph (CXR) available for
      reference at the time of reporting a ventilation-perfusion (V/Q) scan. We
      designed a study to determine whether the availability of a CXR altered the
      interpretation of V/Q scans in our unit. One hundred consecutive V/Q scans were
      reported with and without reference to a CXR by two radiologists and two nuclear
      physicians. The V/Q reports were then compared. Our results show that the
      availability of a CXR has no effect on the V/Q scan report.

PMID- 9515550
TI  - Reproducibility of gastric emptying of a pancake and milkshake meal in normal
      subjects.
AB  - Comparisons of gastric emptying between different centres are difficult because
      of wide variations in methods. Reproducibility of a method is very important
      before it is used to compare different subjects or to assess the effect of
      treatment. The aim of this study was to measure the reproducibility of gastric
      emptying of a solid and liquid meal in normal subjects. Ten males were studied on
      two occasions. After an overnight fast, the subjects ate a radiolabelled solid
      and liquid meal. There were no significant differences in T50 on the 2 days
      (136.6 +/- 23.2 vs 121.3 +/- 26.7 min for solid and 30.7 +/- 12.6 vs 32.6 +/-
      18.7 min for liquid; mean +/- SD). Intra-subject variability was between 7 and
      21% for the solid component and 1.5 and 63% for the liquid component. The mean
      difference in T50 between the 2 days was 15.3 +/- 21.9 min for the solid
      component and -5.1 +/- 19.7 min for the liquid component. Only one difference
      between the T50 results was not in the 95% confidence interval for the liquid
      component. Thus despite some inter- and intra-subject variability, the method
      showed good reproducibility.

PMID- 9515551
TI  - Single crystal biplane equilibrium radionuclide ventriculography: an improved
      planar imaging technique.
AB  - Radionuclide ventriculography in the best septal view is an established method to
      assess both global and regional ventricular function. Additional projections may
      be used to delineate the wall motion of inferior myocardial segments.
      Radionuclide ventriculography was performed in 65 patients using both a single
      plane (in the best septal view) and a biplane technique. The biplane collimator
      allowed simultaneous assessment in two planes 40 degrees apart, allowing
      simultaneous visualization of all four myocardial walls. Seventeen patients with
      regional wall motion abnormalities were detected with the single plane best
      septal view and a further 18 patients with impaired wall motion were identified
      with the biplane collimator (51% of the abnormal ventricles). The additional
      abnormal segments were seen in only the steep lateral projection. Left
      ventricular ejection fraction estimation with the biplane technique remains
      highly reproducible and correlates well with that derived from the best septal
      view. Biplane radionuclide ventriculography improves the detection of inferior
      wall motion abnormalities at no expense of time, and offers the possibility of
      performing two-view stress ventriculography with inotropic agents.

PMID- 9515552
TI  - The effect duration of selective phosphodiesterase inhibitors in the guinea pig.
AB  - The beta-adrenoceptor agonists, isoprenaline, salbutamol and salmeterol, the non
      selective phosphodiesterase (PDE) isoenzyme inhibitors, theophylline, trequinsin;
      the PDE3 isoenzyme inhibitor, milrinone; the PDE3/4 isoenzyme inhibitor,
      benzafentrine; and the PDE4 isoenzyme inhibitors, denbufylline, nitraquazone, RP
      73401, Ro-20-1724, rolipram and tibenelast all induced concentration-dependent
      reversal of prostaglandin F2alpha-induced contraction of guinea-pig superfused
      trachea in vitro. The relaxant response of the non-selective PDE isoenzyme
      inhibitor trequinsin was slow in onset and demonstrated very slow recovery,
      similar to that observed with the long-acting beta2-adrenoceptor agonist,
      salmeterol and the PDE4 inhibitor, RP 73401. The relaxant agonists also
      significantly reversed bombesin-induced bronchospasm in anaesthetised guinea-pigs
      and there was a highly significant correlation between the ability of drugs to
      reverse PGF2alpha-induced contraction of guinea-pig isolated trachea in vitro and
      bombesin-induced bronchoconstriction in vivo. Furthermore, both salmeterol and
      trequinsin demonstrated long lasting bronchodilator responses consistent with the
      in vitro data. These results show that PDE isoenzyme inhibitors demonstrate
      different pharmacodynamic profiles that is not determined by PDE4 inhibitory
      potency and indicate that other factors may be important in this regard.

PMID- 9515553
TI  - Experiences of the 14C-ethanol technique for blood flow measurements in human
      subcutaneous adipose tissue.
AB  - We compared the 14C-ethanol technique and 133Xe-clearance for adipose tissue
      blood flow measurements in young healthy subjects before and after exercise on an
      ergometer bicycle. The results showed a decrease in outflow/inflow ratio of 14C
      ethanol during the basal situation before the exercise, indicating an increased
      blood flow. However, there was a great range of values, and no correlation
      between the 14C-ethanol technique and 133Xe-clearance was found. Our data
      indicate that the 14C-ethanol technique can not be recommended in its current
      form.

PMID- 9515554
TI  - Metabolic features of newly established congenic diabetes-prone BB.SHR rat
      strains.
AB  - The well-known association of hypertension and diabetes mellitus and the lack of
      suitable animal models to study diabetic hypertension prompted us to transfer 4
      chromosomal regions with quantitative trait loci (QTLs) for blood pressure of the
      spontaneously hypertensive SHR rat onto the genetic background of the diabetes
      prone and normotensive BB/OK rat. Four congenic strains developed are named as
      BB. Sa (Chr.1), BB.Bp2 (Chr.18), BB.1K (Chr.20) and BB.Xs (Chr.X). Because the
      systolic blood pressure is significantly elevated in all congenics, renal related
      traits were investigated in serum and urine. Comparing BB/OK and their congenic
      derivatives, significant differences were found in all serum and in 7 out of 8
      urine constituents studied. Most significant differences were found between BB/OK
      and BB.Bp2 rats. Significant differences were also found between the different
      congenic strains indicating that each congenic strain has its own phenotype and
      that each chromosomal region contains most probably further QTLs for some of the
      traits studied.

PMID- 9515555
TI  - Ovarian steroids reduced apoptotic death in SV40 temperature-sensitive mutant
      virus transformed uterine epithelial cells.
AB  - Ovarian steroids have been shown to inhibit uterine cell death in vivo. In this
      study, we investigated whether ovarian steroids regulated cell death in an
      uterine epithelial cell line transformed with SV40 temperature-sensitive (ts)
      mutant virus. To assess cell death rate, cells were grown at permissive
      temperature (34 degrees C) and pulsed with 3H-thymidine. The retention of
      incorporated radioactivity was then examined after a temperature shift to
      nonpermissive temperature (40 degrees C) in the absence or presence of estradiol
      and progesterone. When cells were continuously cultured at 34 degrees C, cell
      number increased rapidly and most of radioactivity was retained in the attached
      cells. However, the temperature shift from 34 degrees C to 40 degrees C resulted
      in a decrease in cell number and radioactivity in attached cells. Estradiol and
      progesterone attenuated this temperature shift-induced cell death. Morphological
      examination with Hoechst 33258 staining revealed that the temperature shift
      increased the percentage of apoptotic death. The treatment of ovarian steroids
      reduced the extent of apoptotic death. Our studies demonstrated that ovarian
      steroids could act directly on uterine epithelial cells to reduce apoptotic death
      in culture.

PMID- 9515556
TI  - Depletion of brain histamine induced by alpha-fluoromethylhistidine enhances
      radial maze performance in rats with modulation of brain amino acid levels.
AB  - We examined the effects of repeated administration of (S)-alpha
      fluoromethylhistidine (FMH), a specific inhibitor of histidine decarboxylase
      (HDC), on radial maze performance and brain contents of histamine and amino acids
      in rats. By daily subcutaneous (s.c.) administration of FMH (100 mg/kg), rats
      showed significant enhancement of a radial maze performance without changes in
      locomotion. Six days after FMH treatment, the histamine levels both in the
      cerebral cortex and diencephalon decreased significantly. However, the glutamate
      and glycine levels significantly increased in the cerebral cortex and
      hippocampus. These results suggest that FMH enhances the acquisition phase of
      radial maze study with the increases in glutamate and glycine levels in the
      cerebral cortex and hippocampus of rats.

PMID- 9515557
TI  - A new spontaneous animal model of NIDDM without obesity in the musk shrew.
AB  - The EDS (early-onset diabetes in suncus) colony has been developed as a new
      closed breeding colony of the musk shrew (Suncus murinus, Insectivora) exhibiting
      a high incidence of spontaneous diabetes mellitus. We investigated the
      characteristic features of diabetic shrews in this colony. All diabetic shrews
      are characterized by glycosuria (Tes-tape value > or = 3+), hyperglycemia (23.3
      +/- 0.8 mmol/l) and polyuria, and they were affected by the age of 3 months.
      Cumulative incidence (64.1% in males and 27.8% in females) was kept intact after
      the age of 3 months. The growth pattern of diabetic shrews was similar to that of
      non-diabetic shrews, and obesity was not consistent in diabetic shrews. The
      intraperioneal glucose tolerance test revealed both impaired glucose tolerance
      and impaired insulin secretion in diabetic shrews. Insulin sensitivity of
      diabetic shrews decreased in the intraperioneal insulin tolerance test. Neither
      severe hypertrophy nor lymphocytic infiltration was observed in pancreatic islets
      of diabetic shrews. These facts suggested that diabetic shrews in the EDS colony
      should be classified as early-onset non-insulin dependent diabetes mellitus
      (NIDDM) without obesity. Early-onset of severe hyperglycemia with impaired
      glucose tolerance is a distinctive character compared with other non-obese NIDDM
      models in rodents. We concluded that the diabetic shrews in the EDS colony are a
      new animal model of human NIDDM without obesity.

PMID- 9515558
TI  - In vitro effects of endothelin-1 on somatostatin and thyrotropin-releasing
      hormone release from the rat stomach.
AB  - The effects of endothelin (ET) 1 on the release of somatostatin (SS) and
      thyrotropin-releasing hormone (TRH) from the rat stomach were studied in vitro.
      The rat stomach was incubated in medium 199 with 1.0 mg/ml of bacitracin (pH 7.4)
      for 20 min. The amounts of SS and TRH released into the medium were measured by
      individual radioimmunoassays. With the addition of ET-1, the release of SS from
      the rat stomach was inhibited significantly in a dose-related manner, whereas TRH
      released from the stomach was enhanced significantly. These effects of ET-1 on SS
      or TRH release were blocked by BQ-485, a blocker of ETA receptor. These findings
      suggest that ET-1 inhibits SS and stimulates TRH release from the rat stomach in
      vitro, and that these effects are mediate via ETA receptor.

PMID- 9515559
TI  - Variations of prostaglandin E2 receptors in hamster's ovary and endometrium
      during estrous cycle.
AB  - The purpose of this study was to determine concurrent ovarian and endometrial
      prostaglandin E2 (PGE2) receptor concentrations throughout the hamster estrous
      cycle. The effect of progesterone (P4) on PGE2 receptor in these two tissues was
      also investigated during in vitro culture. Estrous cycles of mature female
      hamsters were monitored according to the appearance of the vaginal discharge on
      cycle day 1 (D1). Ovaries and uteri were removed from cyclic hamsters at 10:00
      a.m. on each day of the cycle and at 6:00 p.m. on D4 (proestrus). Ovarian and
      endometrial cell membranes were collected and assayed for the specific PGE2
      binding by Scatchard plot analysis, using seven different concentrations of 3H
      PGE2 (0.72-9.1 nM) with or without the presence of unlabelled PGE2 (9.1 microM).
      Ovarian and endometrial tissues of the cyclic hamsters were shown to contain a
      saturable, specific binding site with KD=4.69+/-0.55, and 5.7+/-0.4 nM for ovary
      and endometrium, respectively. Relative binding activity of PGE1 for the PGE2
      binding site was about 28%. PGF2alpha and PGA1 did not compete for the PGE2
      binding site. In ovaries, the PGE2 receptor levels started to increase sharply in
      the evening of D4 and reached maximum in the morning of D1. A precipitous drop of
      PGE2 receptor was observed on D2 followed by gradual decreases on D3 and D4. The
      PGE2 receptor concentrations in endometrium were the lowest in the morning of D4,
      and increased thereafter until a maximal level was reached on D2. Progesterone
      (10 nM) augmented PGE2 receptors in ovarian but not in endometrial tissue during
      24-h in vitro incubation.

PMID- 9515560
TI  - Bovine adrenals and hypothalamus are a major source of proscillaridin A- and
      ouabain-immunoreactivities.
AB  - Besides an isomer of the cardenolide ouabain, a material with a similar HPLC
      retention time as ouabain but cross-reactivating with antibodies against the
      bufadienolide proscillaridin A and inhibiting the sodium pump is known to
      circulate in human blood plasma (B. SICH et al., Hypertension 27, 1073-1078
      (1996).). The concentrations of both substances are known to correlate with the
      blood pressure. It was the intention of this work to localize tissues that
      contain the highest concentrations of the proscillaridin A immunoreactive
      material, to correlate its concentration with that of ouabain and to get
      information whether the concentration of this material simply reflects the number
      of sodium pumps of the tissue extracted. Specific antibodies for each cardiotonic
      steroid were used to test the tissue concentration. This report shows that in
      bovine tissues the distribution pattern of proscillaridin A and ouabain
      immunoreactivities are similar and that hypothalamus and adrenals show the
      highest concentrations. The cross-reactive material did not reflect the number of
      sodium pumps per g of wet weight tissue as measured by [3H]ouabain binding.
      Therefore, it is unlikely that the tissue concentrations in both
      immunoreactivities reflects the tissue capacity of sodium pumps labeled with
      cardiotonic steroids via the blood plasma. The study rather favors the concept
      that two different types of inhibitors of the sodium pump exist within both
      tissues.

PMID- 9515561
TI  - Role of nitric oxide in exercise-induced vasodilation in man.
AB  - Nitric oxide (NO) is a potent endothelium-derived vasodilator, which is known to
      play an important role in the regulation of resting vascular tone in animals and
      humans. However, the degree to which NO is involved in exercise-induced
      vasodilation in the skeletal muscle remains unclear. We studied the effect of N
      monomethyl-L-arginine (L-NMMA) in a randomized, double-blind, placebo controlled
      cross over study in 16 young, healthy volunteers ( 8 male, 8 female) at rest and
      during bicycle exercise stress test. L-NMMA was given as a bolus of 3 mg/kg over
      5 minutes followed by a continuous i.v. infusion of 50 microg/kg/min over 75
      minutes. Subjects underwent a symptom-limited graded bicycle stress test with a
      25 Watt increase in workload every 5 minutes. Skin and muscle blood flow were
      measured by laser Doppler flowmetry. L-NMMA slightly increased mean arterial
      blood pressure and decreased NO exhalation, but had no effect on pulse rate,
      oxygen consumption (VO2), skin or muscle blood flow at rest. Moreover, L-NMMA
      exerted no effect on exercise-induced changes in hemodynamics. Our results
      suggest that submaximal inhibition of NO-synthase with L-NMMA at doses that
      induce moderate hemodynamic changes does not affect exercise induced
      vasodilation.

PMID- 9515562
TI  - Different GABA-receptor types are involved in the 5-HT-induced antinociception at
      the spinal level: a behavioral study.
AB  - The effects of intrathecally (i.t.) administered GABA(A)-receptor antagonist
      picrotoxin or bicuculline on the antinociception produced by i.t. serotonin (5
      HT), gamma-aminobutyric acid (GABA), muscimol--the GABA(A) agonist or baclofen-
      the GABA(B) agonist were investigated and compared using the tail-flick assay in
      rats. The results showed that 1) both i.t. picrotoxin (1.5 nmol) and i.t.
      bicuculline (0.5 nmol) exhibited a partial and later-emerged blockade on the
      antinociception produced by 5-HT (120 nmol) or GABA (1.5 nmol); 2) both i.t.
      picrotoxin and i.t. bicuculline, with the same dosages, completely blocked the
      antinociception produced by muscimol (1.0 nmol), but showed no effects on that
      produced by baclofen (0.3 nmol). The results suggest that GABA may mediate the 5
      HT-induced antinociception at the spinal level, with the GABA(B)-receptors
      exhibiting the effect at the early-stage and the GABA(A)-receptors at the later
      stage of the 5-HT-induced antinociception.

PMID- 9515563
TI  - Effect of ischemia-reperfusion on contractile function of rat urinary bladder:
      possible role of nitric oxide.
AB  - Because there are increasing evidences that nitric oxide (NO) plays important
      roles in ischemia-reperfusion injury in several systems, we investigated the role
      of NO in ischemia-reperfusion injury of the rat urinary bladder. Rat abdominal
      aorta was clamped with a small clip to induce ischemia-reperfusion injury in the
      rat bladder dome. In functional studies, contractile responses to carbachol were
      cumulatively measured after the urinary bladder was treated with various duration
      (0, 30, 60, and 90 min) of ischemia. The injury of rat bladder functioning was
      dependent on ischemic periods. Significant decreases in the Emax (maximum
      contractile response) values were observed in the bladder subjected to 60 or 90
      min ischemia. Furthermore, the subsequent 30 min reperfusion caused additional
      damages of the contractile response in bladder muscles. To investigate the role
      of NO in the ischemia (30 min)-reperfusion (30 min) injury, NG-nitro-L-arginine
      methylester (L-NAME) was injected intraperitoneally 30 min before the ischemia.
      Treatment of L-NAME (30 and 100 mg/kg) partly but significantly prevented the
      reduction contractile responses to carbachol of the rat bladder dome. In
      histological studies, the ischemia-reperfusion caused infiltration of leukocytes
      and rupture of microcirculation in the regions of submucosa and smooth muscle
      without a corresponding sloughing of mucosal cells. The histological damages were
      also prevented by treatment with L-NAME. Therefore, these data suggested that
      ischemia-reperfusion of the urinary bladder may result in dysfunction of the
      contractile response to autonomic nervous system and that nitric oxide may act as
      a cell/tissue damaging agent in ischemia-reperfusion injury.

PMID- 9515564
TI  - Biochemical pharmacology of nonsteroidal anti-inflammatory drugs.
AB  - Aspirin and conventional nonsteroidal anti-inflammatory drugs are nonselective
      inhibitors of cyclooxygenase-1 (COX-1) and COX-2 enzymes. Two classes of
      selective COX-2 inhibitors: (1) sulfonamides, such as L-745,337, and (2)
      tricyclic methyl sulfone derivatives, such as SC58125, have been developed. X-ray
      crystal structures of COX-1 and COX-2 have provided valuable information
      regarding the structural basis for their COX-2 selectivity. These compounds have
      less gastrointestinal complications in animal experiments. Their clinical
      efficacy and side-effects are being evaluated. Salicylate has very weak activity
      against either COX isoform and yet possesses anti-inflammatory actions. Recent
      studies indicate that it suppresses the expression of genes involved in
      inflammation. These activities may provide a plausible explanation for the
      pharmacological dilemma and, furthermore, may represent novel mechanisms for
      controlling inflammation.

PMID- 9515565
TI  - Rethinking receptor-G protein-effector interactions.
AB  - Hundreds of different receptors regulate the activity of effector proteins with
      the assistance of heterotrimeric guanine nucleotide-binding proteins (G
      proteins). The hypothesis that G protein-coupled receptors (R) govern their
      effectors (E) indirectly via a shuttling mechanism involving the exchange of
      heterotrimeric G proteins (G[alpha betagamma]) or parts thereof (G[alpha],
      G[betagamma]) between ephemeral R-G and G-E complexes has become firmly
      established. While there is no direct evidence for the cyclical formation and
      dissociation of these complexes during signalling, experimental changes in second
      messenger production, GTPase activity, and the binding characteristics of
      agonists, antagonists, and guanine nucleotides commonly are believed to reflect
      perturbations in the equilibria between G protein and the other two components.
      However, a growing body of evidence seems to argue against the shuttling model.
      The random, transient association of G protein and receptor is largely
      inconsistent with the binding of agonists to receptors and the allosteric
      regulation of that binding by guanine nucleotides. Also, the prevailing paradigm
      does not readily account for receptor-effector coupling specificity, as the
      promiscuous interaction of most G proteins with both receptors and effectors in
      vitro is at odds with the general failure of G proteins to be shared among
      ostensibly congruous signal transduction pathways in vivo. The latter paradox
      would be obviated by the simultaneous interaction of G protein with both receptor
      and effector. Indeed, various findings indicate that R-G-E complexes do occur.
      How and where in the cell such complexes are assembled and disassembled should
      provide important clues to the true mechanism of G protein-linked transduction.

PMID- 9515566
TI  - Effect of taurine on chelerythrine inhibition of calcium uptake and ATPase
      activity in the rat retina.
AB  - Taurine potentiates calcium uptake in whole retinal homogenates as well as in rod
      outer segments and mitochondrial fractions. The aim of this study was to
      correlate taurine potentiation of calcium uptake with its effects on other
      cellular processes through the use of chelerythrine (CHT), a modulator of protein
      kinase C (PKC), ATPase activity, and, as recently shown, of retinal protein
      phosphorylation. CHT inhibited calcium uptake only when ATP was present, and
      inhibition increased significantly in conditions of ATP excess. Taurine
      potentiated ATP-dependent calcium uptake but decreased the potency of ATP to
      induce uptake activity. CHT inhibition of calcium uptake exhibited similar
      potencies in the presence and absence of taurine, and this inhibition seemed to
      be independent of PKC inhibition. Because of the ATP-dependence of the observed
      effect, total ATPase activity was studied using similar treatments. In the
      absence of taurine, CHT inhibited ATPase activity with the same potency (IC50
      approximately 59.3 microM) as with calcium uptake inhibition (IC50 approximately
      87.9 microM), presenting a possible mechanism of action of CHT. In the presence
      of taurine, no such correlation was observed, suggesting an ATPase-independent
      mechanism of action. In fact, taurine did not potentiate ATPase activity, but
      rather it decreased the potency of CHT inhibition of ATPase, effects incongruent
      with the effects of taurine on calcium uptake and on CHT inhibition of calcium
      uptake. Enzyme kinetic experiments provided more supporting data. Taurine was
      found to cause an increase in the affinity of the ATP substrate for the ATPase
      enzyme, contradicting the aforementioned effect of taurine to decrease the
      potency of ATP to induce calcium uptake. Thus, taurine seems to increase calcium
      uptake through a hitherto unreported mechanism distinct from its modulation of
      ATPase activity.

PMID- 9515567
TI  - Regulation of methionine adenosyltransferase catalytic activity and messenger RNA
      in SH-SY5Y human neuroblastoma cells.
AB  - The human neuroblastoma cell line SH-SY5Y was used to study the regulation of
      methionine adenosyltransferase (MAT II; E.C.2.5.1.6.) catalytic activity and
      transcript levels in cells of neuronal origin. The cells were exposed for 24 hr
      to a medium containing different concentrations of methionine (MAT substrate) as
      well as medium deficient of methionine. Furthermore, cells were treated with
      hydroxycobalamin, SAM, and the competitive MAT inhibitor cycloleucine. The MAT
      catalytic activity was inversely correlated to methionine concentrations, e.g.
      MAT Vmax increased 2-fold in cells grown in methionine-deficient medium as
      compared with cells cultured under standard conditions. Interestingly, MAT Km
      also increased from 9.04 +/- 0.44 to 12.08 +/- 0.83 in the methionine-deficient
      medium. Hydroxycobalamin caused an increase in activity at 40 microM while a
      decrease was observed at higher concentrations (100, 200, and 400 microM).
      Cycloleucine caused a significant inhibition of MAT catalytic activity, i.e. the
      inhibition was approximately 50% in the presence of 4 mM cycloleucine. The
      relevance of these results for the understanding of observations on MAT catalytic
      activity in brains of patients with Alzheimer's disease is discussed.

PMID- 9515568
TI  - Antioxidative properties of organotellurium compounds in cell systems.
AB  - The protective/antioxidative properties of diaryl tellurides were demonstrated in
      cellular systems of increasing complexity. In the presence of glutathione, bis(4
      hydroxyphenyl) telluride (1a), bis(4-aminophenyl) telluride (1d) and bis(2
      carboxyphenyl) telluride (1h) reduced by more than 50% t-butyl hydroperoxide
      induced cell death in lung fibroblast cultures at concentrations below 2 microM.
      Bis(2,6-dimethyl-4-hydroxyphenyl) telluride (2b) reduced by more than 50%
      leukocyte-mediated and phorbol-12-myristate-13-acetate-stimulated damage to Caco
      2 cells at 0.1 microM concentration. As judged by their abilities to reduce
      formation of thiobarbituric acid reactive substances at concentrations close to 1
      microM, diaryl tellurides 1a, 1d and 2b protected rat kidney tissue against
      oxidative damage caused by anoxia and reoxygenation. The organotellurium
      compounds also offered protection after systemic administration. In the presence
      of diaryl telluride 2b (0.1-1 microM), the ischemia/reperfusion-induced vascular
      permeability increase in the hamster cheek pouch was significantly reduced as
      compared with the control. Some of the most active organotellurium cell
      protectants were evaluated for their ability to inhibit formation of the
      inflammatory mediators leukotriene B4 and interleukin-1beta. An inhibitory effect
      on the secretion of these species was seen for compounds 1a and 2b at or above 10
      microM concentrations. The protective effects of diaryl tellurides against t
      butyl hydroperoxide-induced cell injury can be ascribed mainly to the peroxide
      decomposing, glutathione peroxidase-like capacity of the compounds. The chain
      breaking, electron- or hydrogen atom-donating ability of diaryl tellurides seems
      to be the main reason for their protection against leukocyte-mediated cell damage
      in Caco-2 cells and in the oxidatively challenged rat kidney and hamster cheek
      pouch.

PMID- 9515569
TI  - Inhibition of cromolyn-induced phosphorylation of a 78-kDa protein by phorbol
      esters in rat peritoneal mast cells.
AB  - Disodium cromoglycate (cromolyn) is a well documented inhibitor of
      immunologically-induced histamine release from rat peritoneal mast cells and has
      been shown to stimulate the phosphorylation of a mast cell protein of apparent
      molecular mass 78,000 Da (78 kDa), an event which may be involved in terminating
      secretion. Here we aimed to determine the role of the ubiquitous enzyme, protein
      kinase C, in the phosphorylating activity of cromolyn by examining the effects of
      phorbol esters (activators of protein kinase C) on protein phosphorylation in
      [32P]orthophosphate loaded rat peritoneal mast cells. Protein kinase C-activating
      phorbol esters such as 12-O-tetradecanoyl phorbol-13-acetate (TPA) and 4beta
      phorbol 12,13-dibutyrate (PdBu) were found to potently inhibit cromolyn-induced
      phosphorylation when added to mast cells simultaneously with cromolyn (IC50 22
      and 79 nM respectively). 4Alpha-phorbol 12,13-didecanoate (PdD), a phorbol ester
      which does not activate protein kinase C, had no effect on cromolyn-induced
      phosphorylation. Addition of TPA to mast cells previously exposed to cromolyn for
      60 sec (i.e. when 78-kDa protein phosphorylation is maximal) also caused a very
      rapid dephosphorylation of the 78-kDa protein. Phosphorylation of the 78-kDa
      protein can also be induced by dibutyryl cyclic GMP and this action was similarly
      inhibited by TPA and PdBu. Cromolyn inhibited secretion induced by anti-IgE, but
      not by TPA, and thus inhibition of secretion by cromolyn is further correlated to
      its phosphorylation of the 78-kDa protein. The data suggest that the inhibitory
      action of cromolyn on mast cell secretion and phosphorylation of the 78-kDa
      protein are not mediated through a phorbol ester-sensitive protein kinase C, but
      more likely that such an enzyme could be involved in regulating dephosphorylation
      of the 78-kDa protein. Further explanations for this novel dephosphorylating
      activity of phorbol esters are discussed.

PMID- 9515570
TI  - Evidence for co-expression and desensitization of A2a and A2b adenosine receptors
      in NG108-15 cells.
AB  - Using receptor-selective agonists and antagonists, the possible presence of both
      A2a and A2b adenosine receptor subtypes coupled to activation of adenylyl cyclase
      was investigated in NG108-15 neuroblastoma x glioma hybrid cells. The relatively
      non-selective adenosine receptor agonist 5'-(N-ethyl carboxamido)-adenosine
      (NECA; 1 nM-300 microM) produced a biphasic increase in adenylyl cyclase activity
      in cell homogenates, best fitted to two components with high (EC50 0.7 microM)
      and low (EC50 16.0 microM) potency, respectively. The selective adenosine A2a
      receptor agonist CGS-21680 (1 nM-300 microM) also produced a biphasic increase in
      adenylyl cyclase. The NECA-dependent increase in adenylyl cyclase activity was
      almost completely inhibited by the non-selective adenosine receptor antagonist
      xanthine amine congener (XAC; 30 microM), but only partially inhibited by the
      selective A2a adenosine antagonist 8-(3-chlorostyryl)caffeine (CSC; 1 microM).
      Experiments were also performed to investigate the time course of NECA-induced
      desensitization of putative A2a and A2b receptor responses. The A2a-response was
      quantified using 10 microM CGS-21680, whilst the A2b response was quantified
      using 100 microM NECA in the presence of 1 microM CSC. The t0.5 for
      desensitization for each subtype was found to be around 20 min. Neither
      activation (with dibutyryl cAMP; 1 mM) nor inhibition (with H-89; 10 microM) of
      cyclic AMP-dependent protein kinase altered the ability of NECA pretreatment to
      desensitize A2a or A2b receptor-activated adenylyl cyclase. However zinc (200
      microM), an inhibitor of G-protein coupled receptor kinase 2 (GRK2),
      significantly reversed the agonist-induced desensitization of A2a and A2b
      receptor-activated adenylyl cyclase. These experiments suggest the co-existence
      of A2a and A2b receptors coupled in a stimulatory fashion to adenylyl cyclase in
      NG108-15 cells. Furthermore desensitization of A2a and A2b responses occurs at
      the same rate and may involve a G-protein-coupled receptor kinase.

PMID- 9515571
TI  - Frequent coexpression of MRP/GS-X pump and gamma-glutamylcysteine synthetase mRNA
      in drug-resistant cells, untreated tumor cells, and normal mouse tissues.
AB  - Expression of the multidrug-resistance protein gene MRP, which confers non-P
      glycoprotein-mediated multidrug resistance, has been found in many drug-resistant
      variants and tumor samples. Recent studies have demonstrated that MRP functions
      as an ATP-dependent transporter functionally related to the previously described
      glutathione-conjugate (GS-X) pump. We have shown recently that the MRP and gamma
      glutamylcysteine synthetase (gamma-GCS) heavy subunit mRNA levels are
      coordinately overexpressed in cisplatin (CP)-resistant human leukemia cells
      (Ishikawa et al., J Biol Chem 271: 14981-14988, 1996) and frequently co-elevated
      in human colorectal tumors (Kuo et al., Cancer Res 56: 3642-3644, 1996). In the
      present study, we showed the coexpression patterns of thirteen additional human
      drug-resistant cell lines representing different tumor cell origins selected with
      different agents, except for one doxorubicin-selected line which demonstrated
      minor elevation in MRP mRNA with no detectable increase in gamma-GCS mRNA,
      suggesting that the increase of MRP mRNA preceded the increase in gamma-GCS mRNA.
      Furthermore, in seventeen randomly selected untreated tumor cell lines, the
      overall correlation coefficient between MRP and gamma-GCS mRNA levels was 0.861.
      In normal mice, the correlation coefficient of mrp and gamma-gcs mRNA was 0.662
      in fourteen tissues (kidney and liver were not included) analyzed. Kidney and
      liver expressed low levels of mrp relative to gamma-gcs; however, these two
      tissues expressed high levels of a functionally related mrp homologue, mrp2
      (cMoat or cMrp), which may have compensated for the underexpressed mrp in
      maintaining the total GS-X pump activities. Altogether, these results
      demonstrated the frequent coexpression of these two genes in various cell
      settings.

PMID- 9515572
TI  - Retention of marked sensitivity to (S)-4-isopropoxycarbonyl-6-methoxy-3
      (methylthiomethyl)-3,4-di hydroquin oxaline-2(1H)-thione (HBY 097) by an
      azidothymidine (AZT)-resistant human immunodeficiency virus type 1 (HIV-1) strain
      subcultured in the combined presence of quinoxaline HBY 097 and 2',3'-dideoxy-3'
      thiacytidine (lamivudine).
AB  - An azidothymidine (AZT)-resistant virus strain (HIV-1/AZT) (containing the 67 Asp
      --> Asn, 70 Lys --> Arg, 215 Thr --> Phe and 219 Lys --> Gln mutations into its
      reverse transcriptase) was grown in the combined presence of 2',3'-dideoxy-3'
      thiacytidine (3TC, lamivudine) and the nonnucleoside reverse transcriptase
      inhibitor (S)-4-isopropoxycarbonyl-6-methoxy-3-(methylthiomethyl)-3,4-dih
      ydroquinoxaine-2(1H)-thione (quinoxaline HBY 097). Replication of HIV-1/AZT was
      inhibited to a significantly greater extent by the combination of 3TC and
      quinoxaline HBY 097 than by either drug alone. Virus breakthrough was markedly
      delayed in the combined presence of 3TC and HBY 097 at drug concentrations as low
      as 0.05 microg/mL and 0.0025 microg/mL, respectively. The virus that was
      recovered after exposure to the compounds (3TC and HBY 097) individually had
      acquired, in the genetic AZT-resistance background of HIV-1/AZT, 103 Lys --> Glu
      and 106 Val --> Ala mutations. The 103 Lys --> Glu mutation had not been observed
      before. However, both virus mutants retained marked sensitivity to HBY 097. In
      all cases, the genotypic AZT-resistance mutations were maintained in the mutant
      virus RT genomes, and the viruses also remained phenotypically resistant to AZT.
      Given the exquisite potency of a concomitant combination of 3TC and HBY 097 in
      suppressing virus replication, this drug combination should be further pursued in
      clinical trials in HIV-1-infected individuals.

PMID- 9515573
TI  - Pharmacological characterization of adenosine A2B receptors: studies in human
      mast cells co-expressing A2A and A2B adenosine receptor subtypes.
AB  - Characterization of A2B receptors is hampered by the lack of selective
      pharmacological probes and often relies on their relative affinity to agonists
      that are selective at other receptor types. This approach is limited because the
      affinity of A2B receptors for putative A3 agonists has not been determined. Using
      the human erythroleukemia cell line HEL as a cellular model for A2B-mediated
      adenylate cyclase activation, we found the following potencies (pD2) for the non
      selective agonist 5'-N-ethylcarboxamidoadenosine (NECA) (5.65 +/- 0.04), the
      putative A3 agonists N6-benzyl-NECA (4.17 +/- 0.06) and N6-(3-iodobenzyl)-N
      methyl-5'-carbamoyladenosine (IB-MECA) (3.7 +/- 0.02), and the A2A agonist 4-[(N
      ethyl-5'-carbamoyladenos-2-yl)-aminoethyl]-phenylpropionic acid (CGS21680) (2.8
      +/- 0.1). Because of the lack of a selective agonist, characterization of A2B
      receptor function is difficult in cells co-expressing A2A receptors. In the human
      mast cell line HMC-1, NECA induced cAMP accumulation with a concentration
      response relationship best fitted to a two-sited model (pD2 7.69 +/- 0.42 and
      5.92 +/- 0.21 for high- and low-affinity sites), suggesting the presence of both
      A2A and A2B receptors in these cells. We demonstrated that A2B receptors can be
      selectively activated with NECA in the presence of the selective A2A antagonist 5
      amino-7-(phenylethyl)-2-(2-furyl)-pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c
      ]pyrimidine (SCH 58261). Under these conditions, the concentration-response
      relationship of NECA for cyclic AMP accumulation was now best fitted to a one
      site model (pD2 5.68 +/- 0.03, Hill slope 0.93 +/- 0.06, 95% confidence intervals
      0.8 to 1.06) corresponding to selective activation of A2B receptors. Using the
      approaches developed in this study, we determined that A2B, and not A2A or A3,
      receptors account for all the calcium mobilization induced by NECA in HMC-1
      cells.

PMID- 9515574
TI  - Antimitotic and tubulin-interacting properties of vinflunine, a novel fluorinated
      Vinca alkaloid.
AB  - This study aimed to define the mechanism of action of vinflunine, a novel Vinca
      alkaloid synthesised from vinorelbine using superacidic chemistry and
      characterised by superior in vivo activity to vinorelbine in preclinical tumour
      models. In vitro vinflunine cytotoxicity proved dependent on concentration and
      exposure duration, with IC50 values (72-hr exposures) generally ranging from 60
      300 nM. Vinflunine induced G2 + M arrest, associated with mitotic accumulation
      and a concentration-dependent reduction of the microtubular network of interphase
      cells, accompanied by paracrystal formation. These effects, while comparable to
      those of vincristine, vinblastine or vinorelbine, were achieved with 3- to 17
      fold higher vinflunine concentrations. However, vinflunine and the other Vincas
      all inhibited microtubule assembly at micromolar concentrations. Vinflunine, like
      vinblastine, vincristine and vinorelbine, appeared to interact at the Vinca
      binding domain, as judged by proteolytic cleavage patterns, and induced tubulin
      structural changes favouring an inhibition of GTP hydrolysis. However, vinflunine
      did not prevent [3H]vincristine binding to unassembled tubulin at concentrations
      < or = 100 microM, and only weakly inhibited binding of [3H]vinblastine or
      [3H]vinorelbine. Indeed, specific binding of [3H]vinflunine to tubulin was
      undetectable by centrifugal gel filtration. Thus, the comparative capacities of
      these Vincas to bind to or to interfere with their binding to tubulin could be
      classified as: vincristine > vinblastine > vinorelbine > vinflunine. By
      monitoring alkylation of sulfhydryl groups, differential effects on tubulin
      conformation were identified with vinflunine and vinorelbine acting similarly,
      yet distinctively from vinblastine and vincristine. Overall, vinflunine appears
      to function as a definite inhibitor of tubulin assembly, while exhibiting
      quantitatively different tubulin binding properties to the classic Vinca
      alkaloids.

PMID- 9515575
TI  - Co-detection by two imidazoline receptor protein antisera of a novel 85
      kilodalton protein.
AB  - Imidazoline receptors (I-receptors) are considered as potential therapeutic
      targets for a spectrum of stress-induced illnesses. Yet, I-receptors remain
      poorly defined at the molecular level. In this study, candidate imidazoline
      receptor proteins were compared using two imidazoline receptor-selective antisera
      of diverse origins. One antiserum was derived from affinity-purified imidazoline
      binding protein. The second antiserum was produced as an anti-idiotypic
      antiserum, from purified IgG selective for imidazolines. Despite such diverse
      origins, both antisera co-identified an 85 kDa band on western blots from a
      variety of tissues. The integrity of the 85 kDa band was dependent on protection
      by eight different protease inhibitors. Other proteolytic breakdown products
      (obtained after homogenization with only one protease inhibitor) were comparable
      in size to previously reported smaller immunoreactive bands. The full-size 85 kDa
      band was also enriched in plasma membrane fractions and abundant in rat PC12
      cells and brain regions known to be abundant in I1 binding sites. Furthermore,
      the immunodensity of the 85 kDa band, against anti-idiotypic antiserum, was
      linearly correlated with reported I1 site radioligand Bmax values (r2 = 0.8736, P
      = 0.0002) across nine rat tissues. Therefore, a possible candidate for the full
      length imidazoline receptor(s) appears to be an 85 kDa protein.

PMID- 9515576
TI  - Cell-mediated biotransformation of S-nitrosoglutathione.
AB  - Spontaneous release of nitric oxide (NO) from S-nitrosothiols cannot explain
      their bioactivity, suggesting a role for cellular metabolism or receptors. Using
      immortalised cells and human platelets, we have identified a cell-mediated
      mechanism for the biotransformation of the physiological S-nitrosothiol compound
      S-nitrosoglutathione (GSNO) into nitrite. We suggest the name "GSNO lyase" for
      this activity. GSNO lyase activity varied between cell types, being highest in a
      fibroblast cell line and lowest in platelets. In NRK 49F fibroblasts, GSNO lyase
      mediated a saturable, GSNO concentration-dependent accumulation of nitrite in
      conditioned medium, which was inhibited both by transition metal chelators, and
      by subjecting cells to oxidative stress using a combination of the thiol oxidant
      diamide and Zn2+, a glutathione reductase inhibitor. Activity was resistant,
      however, to both acivicin, an inhibitor of gamma-glutamyl transpeptidase (EC
      2.3.2.2), and to ethacrynic acid, an inhibitor of Pi class glutathione-S
      transferases (EC 2.5.1.18), thus neither of these enzymes could account for NO
      release. Although GSNO lyase does not explain the platelet-selective
      pharmacological properties of GSNO, cellular biotransformation suggests
      therapeutic avenues for targeted delivery of NO to other tissues.

PMID- 9515577
TI  - Cellular interactions of 5-fluorouracil and the camptothecin analogue CPT-11
      (irinotecan) in a human colorectal carcinoma cell line.
AB  - CPT-11 (irinotecan) is a DNA topoisomerase I inhibitor active against metastatic
      colorectal carcinoma. We investigated, in a human colon carcinoma cell line, HT
      29, the effects of CPT-11 and 5-fluorouracil (5FU) combinations. A strong
      synergism between CPT-11 and 5FU was observed after sequential exposure and only
      additivity or antagonism after simultaneous exposure. When cells were first
      exposed to 5FU, the product of cellular CPT-11 concentrations versus time (CxT)
      was 6895 +/- 1020 pmol x hr/10(6) cells, while it was 3875 +/- 121 pmol x
      hr/10(6) cells with CPT-11 alone (p < 0.01). The same phenomenon was observed
      with SN-38: 148.2 +/- 49.5 versus 83.4 +/- 23.6 pmol x hr/10(6) cells (p < 0.05).
      Consequently, the formation of protein-DNA complexes was 1.4 times greater with
      5FU pretreatment than with CPT-11 alone (p = 0.03). Moreover, the incorporation
      of 5FU derivatives into DNA was multiplied by a factor of 1.5 24 hr after CPT-11
      exposure. When cells were first incubated with CPT-11, the decrease in
      thymidylate synthase (TS) activity was identical to that obtained after 5FU
      exposure (1.09 to 0.023 pmol/min/mg protein), but this decrease persisted for 24
      hr (0.014 pmol/min/mg protein) (p = 0.035). At the same time, a 1.8-fold increase
      in the incorporation of 5FU derivatives into DNA and a 2-fold increase in DNA
      protein complex formation were evidenced. With the two sequential associations,
      we observed a persistent S-phase arrest, as compared with CPT-11 alone. These
      results suggest that CPT-11 and 5FU combinations are of clinical interest, and
      mechanisms of interaction between the two drugs seem to be multifactorial.

PMID- 9515579
TI  - Differential characterization of binding sites for adenine and uridine
      nucleotides in membranes from rat lung as possible tools for studying P2
      receptors in lung.
AB  - Nucleotide receptors (P2 receptors) are involved in stimulating Cl- secretion in
      airway epithelia. These receptors may play a key role in development of new
      therapeutic strategies in the treatment of cystic fibrosis. However, the
      diversity of nucleotide binding sites in lung tissue has not yet been clarified.
      Here we studied the characteristics of various nucleotide binding sites in rat
      lung membranes by equilibrium binding analysis of several P2 receptor specific
      ligands. Displacement studies revealed a recognition site for adenosine 5'-O-(1
      thiotriphosphate) ([35S]ATPalphaS; Kd 243 nM). From this site the ligand is
      readily displaced by adenosine 5'-O-(2-thiodiphosphate) (ADPbetaS), a typical
      agonist for P2Y1 receptors and also by alpha,beta-methylene adenosine 5'
      triphosphate (alpha,beta-MeATP), a typical agonist for P2X receptors.
      [3H]alpha,beta-MeATP labelled specific binding sites (Kd 56 nM) in rat lung
      membranes. Analysis of binding of [3H]UTP to lung membranes revealed a high
      affinity binding site (Kd 44 nM). Membrane-bound [3H]UTP was not displaced even
      by high concentrations of ATP, indicating no common binding site for UTP and ATP.
      Furthermore, specific binding of P-1,P-4-di(adenosine 5')tetraphosphate
      ([3H]Ap4A; Kd 91 nM) was found in lung membranes. Thus, we demonstrate at least
      four distinct types of nucleotide binding sites in lung membranes: Two have
      characteristics comparable to P2X and P2Y1 receptors, while two further sites
      still have to be identified, one binding Ap4A and the other binding UTP very
      specifically.

PMID- 9515578
TI  - Stimulatory effects of vanadate on amylase release from isolated rat pancreatic
      acini.
AB  - The effects of vanadate on exocrine pancreatic function were examined in isolated
      rat pancreatic acini. Vanadate caused a concentration-dependent stimulation of
      amylase release above a concentration of 1 mM. Co-incubation of vanadate with
      vasoactive intestinal polypeptide, 8-bromoadenosine 3':5'-cyclic monophosphate,
      and the Ca2+ ionophore A23187 produced a synergistic pattern of amylase release,
      whereas co-incubation with cholecystokinin octapeptide (CCK-8), carbamylcholine,
      and 12-O-tetradecanoylphorbol 13-acetate produced an additive effect. Vanadate
      alone had no influence on acinar cyclic AMP content, Ca2+ efflux, or
      intracellular Ca2+ concentration. However, preincubation with vanadate prevented
      the plateau phase of CCK-8-induced Ca2+ transient increase from returning to
      baseline. Moreover, depletion of the intracellular Ca2+ pool by pretreatment of
      acini with CCK-8 in Ca2+-free medium (plus ethyleneglycol bis[beta
      aminoethylether]-N,N'-tetraacetic acid) had no effect on subsequent stimulation
      by vanadate, although it abolished the response to both CCK-8 and carbamylcholine
      stimulation. The protein kinase C (PKC) inhibitors staurosporine and calphostin C
      significantly inhibited vanadate-stimulated amylase release, whereas the protein
      tyrosine kinase inhibitor genistein had no inhibitory effect. Moreover, vanadate
      caused a significant translocation of PKC from cytosol to membrane fraction in
      pancreatic acinar cells. This translocation was inhibited significantly by
      staurosporine and calphostin C but not by genistein. These results suggest that
      vanadate acts directly on pancreatic acini and stimulates amylase release by
      activating PKC without an effect on Ca2+ mobilization, cyclic AMP, or protein
      tyrosine kinase.

PMID- 9515580
TI  - In vitro enzymatic processing of radiolabelled big ET-1 in human kidney.
AB  - We have investigated enzymatic processing of big ET-1 in sections of human renal
      cortex by examining selected binding characteristics of the radiolabelled
      precursor and cleaved peptide. Sections of histologically normal human kidney
      obtained from patients undergoing nephrectomy for hypernephroma (50-74 years, N =
      10, male or female) were incubated with 0.1 nM [125I]-ET-1, [125I]-Tyr13 big ET-1
      or [125I]-Tyr31 big ET-1 in culture media at 37 degrees to facilitate enzymatic
      activity. Specific binding measured from sections incubated with [125I]-Try13 big
      ET-1 (which would yield [125I]-ET-1 on enzymatic cleavage) was 39.7 +/- 2.5%.
      This was significantly reduced to 19.0 +/- 2.0% following co-incubation with 10
      microM thiorphan, an inhibitor of neutral endopeptidase (NEP) but not the
      putative endothelin converting enzymes (ECE). No further reduction in specific
      binding was obtained with 100 microM thiorphan, indicating that this is a maximal
      effect. However phosphoramidon (100 microM), an inhibitor of ECE and NEP, almost
      abolished specific binding, indicating that both NEP and ECE cleave big ET-1 in
      the kidney. No specific binding was detected when sections were labelled with
      [125I]-Tyr31 big ET-1 (which would be expected to yield [125I] labelled C
      terminal fragment). Binding of the product of processed [125I]-Tyr13 big ET-1 was
      inhibited mainly by the ET(B) selective antagonist (BQ788 = 75.1 +/- 2.1%
      inhibition; FR139317 = 9.7 +/- 7.3% inhibition), consistent with the predominance
      of this subtype in human kidney. We conclude that big ET-1 is processed by NEP
      and ECE in human kidney and that the cleaved product binds predominantly to the
      ET(B) receptor subtype. ECE may be a therapeutic target in the attenuation of
      renal diseases in which ET-1 has been implicated.

PMID- 9515581
TI  - Drug-metabolizing enzymes in rat liver myofibroblasts.
AB  - The myofibroblast is considered to be a key component in the pathogenesis of
      hepatic fibrosis. There is a need for therapeutic intervention in hepatic
      fibrosis, and, to date, the number of efficacious anti-fibrotic drugs is
      negligible. At best, the current therapeutic modalities reduce liver enzymes, an
      indicator of liver damage, but cannot reduce or prevent fibrosis. We have
      described the anti-fibrotic effect of pentoxifylline in an experimental model of
      hepatic fibrosis. Evidence suggests that, in addition to pentoxifylline itself,
      at least two of the metabolites of pentoxifylline are of therapeutic interest. We
      have reported that one of these metabolites (M-1) has a biological activity
      similar to that of its parent drug. The second metabolite (M-1R) has been
      reported to be more potent than the parent drug. Recent evidence suggests that
      inhibition of cytochrome P450 1A2 (CYP1A2) results in higher levels of
      pentoxifylline and M-1 and may be responsible for the production of the novel,
      potent metabolite (M-1R). We therefore investigated whether the myofibroblast,
      the cell with a crucial role in fibrosis, contains drug-metabolizing enzymes and
      thus may play a critical role in the anti-fibrotic actions of pentoxifylline. Our
      results showed that myofibroblasts contain aryl hydrocarbon hydroxylase activity,
      ethoxyresorufin O-deethylase activity, and methoxyresorufin O-demethylase
      activity. The results presented here also indicate that aryl hydrocarbon
      hydroxylase and methoxyresorufin O-demethylase activities can be increased by
      treatment of cells with dibenzanthracene, an inducer of CYP1A activities.

PMID- 9515582
TI  - Effects of camptothecin, a topoisomerase I inhibitor, on Plasmodium falciparum.
AB  - Currently, the treatment of falciparum malaria is seriously compromised by
      spreading drug resistance. We studied the effects of camptothecin, a potent and
      specific topoisomerase I inhibitor, on erythrocytic malaria parasites in vitro.
      In Plasmodium falciparum, camptothecin trapped protein-DNA complexes, inhibited
      nucleic acid biosynthesis, and was cytotoxic. These results provide proof for the
      concept that topoisomerase I is a vulnerable target for new antimalarial drug
      development.

PMID- 9515583
TI  - Can asthma be studied in the urine?

PMID- 9515584
TI  - Latex allergens.

PMID- 9515585
TI  - Association study of asthma and atopy traits and chromosome 5q cytokine cluster
      markers.
AB  - BACKGROUND: Linkage studies have provided evidence for the presence of gene(s) in
      the 5q cytokine cluster region which control total serum immunoglobulin E (IgE)
      concentration, and bronchial hyperreactivity (BHR). However, the identification
      of the gene(s) involved has been confounded by the lack of power of the published
      linkage studies and the presence of multiple candidate genes mapped to the
      region. OBJECTIVE: To define the important loci on 5q31-33 which are implicated
      in the control of total serum IgE and BHR through a case/control study of
      association. METHODS: We performed an association study between 11 polymorphic
      markers (spanning the region 5q31.1-33.1) and total serum IgE and BHR traits. A
      case/control sample of 181 individuals was drawn from a larger set of 2415
      adults, sampled at random from a district in Nottingham, UK. Half of the subjects
      in this case/control sample were hyperreactive to methacholine and asthmatic
      (cases), while the other half were non-reactive and non-asthmatic (controls).
      Association analysis was performed using the non-parametric chi-squared and Mann
      Whitney U-tests. RESULTS: We observed no evidence of strong allelic association
      between any of the above markers and the studied traits. Markers D5S404,
      interferon regulatory factor 1 (IRF-1) and D5S210 showed evidence of borderline
      association with BHR (P = 0.04, 0.03 and 0.04 respectively), and D5S404 showed
      borderline significance with IgE levels (P = 0.029). CONCLUSIONS: This study
      presents evidence against the presence of a strong association between markers
      mapped to 5q31-33 and either BHR or total serum IgE. The significance of the
      weaker associations observed with markers D4S404, IRF-1 and D5S210 is not clear.
      Whether this represents a type I error secondary to multiple hypothesis testing
      or a true association is uncertain.

PMID- 9515586
TI  - Linkage and allelic association of atopy and markers flanking the IL4-receptor
      gene.
AB  - BACKGROUND: Atopy, a clinical syndrome characterized by heightened IgE
      responsiveness, is largely determined by genetic factors. The disease may well be
      heterogeneous but the mode of inheritance is unknown. Several genes have been
      named which affected IgE responsiveness. However, results are conflicting
      reflecting heterogeneity and a complicated inheritance pattern of the atopic
      syndrome. In 1994 linkage of the 5q32 gene region and elevated total IgE levels
      were reported, leaving the IL4 gene as a prominent candidate. OBJECTIVES: We were
      interested in a possible involvement of the IL4-receptor gene in the development
      of atopy. METHODS: We employed sib-pair linkage analysis using highly polymorphic
      microsatellite markers within and flanking the IL4 receptor gene in atopic
      families, characterized for specific sensitization to inhalant allergens and
      elevated total serum IgE. Allele sizes were determined for all microsatellite
      probes to allow transmission disequilibrium analysis. RESULTS: We found
      significant sharing of maternal but not paternal alleles in affected sibs from
      two independent populations, both of which presented enhanced IgE responsiveness.
      Linkage and maternal inheritance could be confirmed by transmission
      disequilibrium analysis. CONCLUSIONS: We conclude from our findings that maternal
      inheritance of a gene in the chromosome 16p12 region increases the risk for
      enhanced IgE responsiveness. The most prominent candidate in this region is
      represented by the IL4 receptor gene.

PMID- 9515587
TI  - HLA class II DRB1, DQB1 and DPB1 genotypic associations with peanut allergy:
      evidence from a family-based and case-control study.
AB  - BACKGROUND: Peanut is one of the most common foods provoking allergic reactions
      and is the most frequent cause of fatal and near-fatal food-induced anaphylaxis.
      However, as yet, little is known of the genetic and immunological mechanisms
      which underly peanut allergy. OBJECTIVE: Based on findings in other allergic
      diseases, we have investigated whether particular human leucocyte antigen (HLA)
      class II genetic polymorphisms contribute to the development of peanut allergy.
      METHODS: All individuals from 37 families each containing one or more peanut
      allergic individuals, plus nine unrelated patients (161 individuals in total,
      defined as the study group) were typed for the HLA class II DRB1, DQB1 and DPB1
      loci, by PCR-based techniques. Genotype frequencies were compared with those
      found in 293 unrelated controls. RESULTS: Four class II genotypes (DRB1*08 (13.7%
      vs 4.8%; Pc = 0.026), DRB1*08/12 tyr 16 (22.4% vs 8.2%; Pc = 0.021), DQB1*04
      (12.2% vs 2.7%; Pc = 0.0026) and DPB1*0301 (49.1 vs 22.5%; Pc = 0.00062)) were
      present at a significantly higher frequency in the study group compared with
      controls. Three of these genotypes (DRB1*08 (18.0%; Pc = 0.027), DRB1*08/12 tyr16
      (24.0%; Pc = 0.029) and DQB1*04 (16.7%; Pc = 0.0029)) were also significantly
      increased in peanut allergic individuals compared with controls. In addition, two
      genotypes (DPB1*0101 and 0201) were significantly decreased in frequency in the
      overall study group, but not specifically in peanut allergic individuals.
      CONCLUSION: While other genetic factors may be important, results from this study
      indicate that HLA class II genetic polymorphism may play a role in determining
      susceptibility to peanut allergy.

PMID- 9515588
TI  - Peanut allergic subjects' peripheral blood mononuclear cell proliferative
      responses to crude peanut protein.
AB  - BACKGROUND: Peanut allergy is characterized by a high frequency of severe and
      occasionally fatal reactions. OBJECTIVE: To determine if there are features of
      the in vitro cellular response that may account for the observed severity of
      peanut allergy. METHODS: Skin-prick testing (SPT), RAST assay of serum peanut
      specific and total IgE and mixed peripheral blood mononuclear cells (PBMC)
      proliferative responses to crude peanut protein were measured in 44 peanut
      allergics with varying severity of clinical reactions. PBMC responses of 13 non
      peanut allergic controls (six atopic) were also studied. RESULTS: Subjects' PBMCs
      proliferated more than controls', even without stimulation. Subjects' PBMC
      proliferative responses did not correlate with clinical severity, SPT weal size
      or peanut-specific IgE levels. Controls' PBMCs did not respond to peanut. There
      was no correlation between PBMC response and time since last reaction to peanut.
      Subjects' PBMCs responded more than controls, to mitogen as well as allergen.
      Proliferation increased with increasing concentration of peanut protein (P <
      0.0001). CONCLUSION: PBMCs of peanut allergics demonstrate a dose-dependent
      response to peanut which does not correlate with clinical severity, SPT reaction
      or levels of peanut specific IgE. The response is antigen-specific. Peanut
      protein is not mitogenic and is not acting as a superantigen. While there are non
      specific differences in the PBMC responses of peanut allergic individuals
      compared with atopic and non-atopic controls, these differences do not explain
      the unique severity of peanut allergy.

PMID- 9515589
TI  - Immune-reactivity of recombinant isoforms of the major house dust mite allergen
      Der p 2.
AB  - BACKGROUND: Recombinant Der p 2, expressed in yeast, lacked reactivity with 5
      monoclonal antibodies against natural Der p 2. OBJECTIVE: The aim of this study
      was to investigate whether the lack of reactivity with recombinant Der p 2 can be
      explained by the existence of isoforms. METHODS: By site-directed mutagenesis
      three recombinant isoforms of Der p 2 were produced. Reactivity with monoclonal
      antibodies and human IgE was analysed by means of RAST and RAST-inhibition.
      RESULTS: All five monoclonals that lacked reactivity with the originally selected
      isoform, showed reactivity upon replacement of aspartic acid by asparagine at
      position 114. The other two substitutions (at position 26 and 47) had no effect.
      Binding of human IgE (n = 10) was not significantly influenced by the isogenetic
      variation at position 114. CONCLUSIONS: Monoclonal antibodies raised against
      natural Der p 2 can sometimes discriminate between different isoforms, allowing
      the study of the natural occurrence of isoforms. For application in allergen
      measurement assays, non-discriminating monoclonal antibodies should be selected.

PMID- 9515590
TI  - Molecular analysis of DRB and DQB1 alleles in German spina bifida patients with
      and without IgE responsiveness to the latex major allergen Hev b 1.
AB  - BACKGROUND AND OBJECTIVE: Spina bifida patients are at a high risk of developing
      latex allergy. Recently, we found a relationship between the IgE responsiveness
      to latex allergen hevein and human leucocyte antigen (HLA) alleles DRB1*04(DR4)
      as well as DQB1*0302(DQ8). This study was carried out to investigate the
      association between HLA class II alleles and the specific IgE response to latex
      allergen Hev b 1 in spina bifida patients. METHODS: Blood samples from 103
      unrelated German spina bifida patients exposed to latex products and from 90
      unsensitized controls were examined. Genomic DNA isolation followed by HLA-D
      specifc polymerase chain reaction (PCR) amplification was used to perform HLA
      typing of allelic polymorphisms in exon 2 of DQB1 and of DRB1,3,4,5 with sequence
      specific oligonucleotide probes (SSOPs). RESULTS: Fifty-one out of 103 spina
      bifida patients were found to have anti-latex IgE antibodies; 40 had also anti
      Hev b 1 antibodies. Further, we observed that 80% of the Hev b 1 responders
      underwent five or more surgeries whereas 55% of the Hev b 1 non-responders and
      75% of the latex-non-responders underwent less than five surgical interventions.
      From the latex-sensitized group 33% showed an elevated phenotype frequency of
      DRB1*0701(DR7) when compared with unsensitized patients (12%, P = 0.0095, Pc =
      NS) and with controls (17%; P = 0.035, Pc = ns). Fifteen out of 40 Hev b 1
      responders also exhibited an elevated DR7 frequency when compared with latex
      sensitive but Hev b 1-negative patients (38% vs 18%, P = NS) or with unsensitized
      controls (38% vs 17%, P = 0.013, Pc = NS). CONCLUSIONS: Although we found that
      the DRB1*0701 (DR7) phenotype frequency was elevated in SB patients with latex-
      as well as with Hev b 1-IgE responsiveness, the analyses of the other class II
      alleles clearly demonstrate that the HLA-D region does not play a major role in
      the pathogenetic way of sensitization to Hev b 1.

PMID- 9515591
TI  - GC/MS analysis of urinary excretion of 9alpha,11beta-PGF2 in acute and exercise
      induced asthma in children.
AB  - BACKGROUND: 9Alpha,11beta-prostaglandin (PG) F2 is an initial metabolite of PGD2
      which has a potent bronchoconstrictive activity. OBJECTIVES: We measured the
      urinary levels of 9alpha,11beta-PGF2 in asthmatic children to investigate its
      role in not only acute asthmatic attack in a time course study but also in
      exercise-induced asthma (EIA). METHODS: In the acute asthma study, 30 asthmatic
      children were examined. Urine samples were collected on the first, third, and
      sixth days. Urinary levels of 9alpha,11beta-PGF2 were measured with gas
      chromatography mass spectrometry using the electron impact method. In the
      exercise challenge study, 14 children with EIA and 14 children without EIA were
      studied. Urine samples were collected before exercise challenge, and at 1 h, and
      5 h after exercise challenge. Urinary levels of 9alpha,11beta-PGF2 were measured.
      RESULTS: Elevated urinary levels of 9alpha,11beta-PGF2, which were observed on
      the first day when treatment was started in the hospital, were gradually
      decreased on the third day (P < 0.05), and on the sixth day (P < 0.01). A
      significant correlation between urinary levels of 9alpha,11beta-PGF2 and symptom
      scores (P < 0.005) was observed on the first day. In EIA, there was a significant
      increase in urinary levels of 9alpha,11beta-PGF2 at 1 h (P < 0.01) and at 5 h (P
      < 0.01) after exercise challenge, but not in the children without EIA.
      CONCLUSION: 9Alpha,11beta-PGF2 may be involved in the pathogenesis of acute and
      exercise-induced asthma in children.

PMID- 9515592
TI  - Differences in cellular infiltrates in the adenoid of allergic children compared
      with age- and gender-matched controls.
AB  - BACKGROUND: Allergic sensitization of the airways occurs in the mucosa of the
      shock organ, or in the lymphatic stations draining these structures. The
      lymphatic structure closest to the nasal mucosa is the adenoid. OBJECTIVES: The
      objective of this study was to find evidence for our hypothesis that allergic
      sensitization can occur in the adenoid. Of special interest, in this context are
      cell types involved in antigen-allergen presentation (e.g. Langerhans cells) and
      effector cells of allergic disease. METHODS: In this study cellular infiltrates
      in adenoids of 16 allergic patients and 16 age- and gender-matched controls were
      evaluated. The number of cells positive for CD1a, CD4, CD8, CD-68, chymase,
      tryptase, IgE, MBP and cells positive for interleukin (IL)-4 were determined
      using immunohistochemical staining techniques. The epithelium, follicles and the
      interfollicular spaces were evaluated separately. RESULTS: When comparing the two
      groups a significant increase in cells positive for CD1a was found in
      interfollicular spaces of the allergic group (P = 0.008). CD1a+ cells in the
      follicular space and eosinophils in the interfollicular space showed a trend to
      be more numerous in the allergic group (P = 0.02 and P = 0.05, respectively). The
      other cell types investigated did not show significant differences between the
      groups. CONCLUSIONS: The results of this study show for the first time that cells
      involved in allergic sensitization and allergic disease differ in the adenoid of
      allergic children compared with controls. These findings support our hypothesis
      that allergic sensitization takes place in the adenoid. Furthermore, this study
      confirms that CD1a+ (Langerhans) cells are involved in allergic disease.

PMID- 9515593
TI  - Histamine release from bronchoalveolar lavage cells from asthmatic subjects after
      allergen challenge and relationship to the late asthmatic response.
AB  - BACKGROUND: Metachromatic cells obtained from asthmatic subjects demonstrate
      increased spontaneous and stimulated histamine release in vitro. Their ability to
      synthesize and store proinflammatory cytokines has focused renewed interest on
      their role in asthma. OBJECTIVE: The late asthmatic response provides a useful
      model of clinical asthma. The aim of the study was to examine metachromatic cell
      derived mediators and histamine releasability in vitro after in vivo allergen
      exposure in atopic subjects with and without asthma and relate them to the type
      of physiological response observed. METHODS: Bronchoalveolar lavage (BAL) cells
      were obtained 4 h after challenge from asthmatics exhibiting a single early
      response (EAR, n = 5), a dual response (LAR, n = 7), unchallenged (basal, n = 5),
      atopic non-asthmatic (ANA, n = 6) and non-atopic non-asthmatics (normal, n = 5).
      BAL histamine and tryptase concentrations and in vitro histamine release (HR)
      after stimulation with anti-IgE, allergen, A23187, conconavalin A and substance P
      were compared. RESULTS: Metachromatic cell numbers were lower in normal controls
      compared with all asthmatic groups and in LAR compared with EAR. Metachromatic
      cell derived mediators were higher in asthmatic compared with normal subjects.
      Spontaneous HR in LAR (20.5 +/- 5.0%) was lower than EAR (29.5 +/- 3.9%) and ANA
      (30.2 +/- 1.4%) (P < 0.05). No differences were seen in stimulated HR between EAR
      and LAR. HR in ANA stimulated with anti-IgE was greater than LAR (P < 0.05). HR
      in ANA stimulated with anti-IgE was greater than LAR (P < 0.05). After
      stimulation with ionophore A23187 (1 microM), release was greater in LAR compared
      with basal (P < 0.05) and no different at 5 microM. All subject groups responded
      to substance P (SP) but was significantly more in the asthmatic subjects compared
      to normal controls (P < 0.05). Allergen challenge did not modify the response of
      asthmatic subjects to SP. CONCLUSION: Functional differences in metachromatic
      cell reactivity are present in atopic subjects 4h after in vivo allergen exposure
      which relate to the physiological response observed after this time and suggest
      that there is ongoing metachromatic cell degranulation subjects who subsequently
      develop LAR.

PMID- 9515594
TI  - Prospective, double-blind, placebo-controlled, multicentre study on the effect of
      high-dose, intravenous immunoglobulin in children and adolescents with severe
      bronchial asthma.
AB  - OBJECTIVE: In order to study the effect of high-dose, intravenous immunoglobulin
      (i.v.IG) in severe childhood asthma, we investigated 31 children and adolescents
      (15 girls, 16 boys) aged 9-22 years (median age of 14 years) suffering from
      severe bronchial asthma. METHODS: In a prospective, double-blind fashion,
      patients received either four doses of i.v.IG (1 g/kg body weight) or identical
      doses of intravenous human serum albumin. The first two doses were given on two
      consecutive days, followed by two further doses at 4 week intervals. RESULTS:
      There was no statistical difference in the actively treated group when compared
      with the placebo group in symptom-score, bronchial hyperreactivity or peak-flow
      variability. There was a trend for fewer total days of upper respiratory tract
      infections and also symptom-scores in the i.v.IG group but these did not reach
      statistical significance. CONCLUSION: Our data indicate that treatment with
      i.v.IG in asthmatic children did not show a significant reduction in the
      incidence of upper respiratory tract infections, but the patients who did have
      upper respiratory infections in the i.v.IG-group appear to have less protracted
      infections. Severity and bronchial hyperreactivity do not seem to be affected by
      the treatment as performed in our study.

PMID- 9515595
TI  - Expression and localization of the inducible isoform of nitric oxide synthase in
      nasal polyp epithelium.
AB  - BACKGROUND: The pathogenesis of nasal polyp disease is poorly understood. Recent
      evidence has suggested that nitric oxide (NO), an endogenous soluble gas
      vasodilator and inflammatory mediator, may be synthesised within the nasal
      cavity. Three nitric oxide synthase isoforms have been identified in humans, with
      the inducible isoform (iNOS) generally expressed in the setting of inflammation.
      OBJECTIVE: The aim of this study was to detect and localize iNOS expression in
      nasal polyp tissue, and compare these findings with normal nasal turbinate
      tissue. METHODS: We examined the expression and localisation of inducible nitric
      oxide synthase (iNOS) in human nasal airway specimens from patients undergoing
      elective nasal turbinectomy (n = 5) or nasal polypectomy (n = 5). iNOS mRNA
      expression was determined by semi-quantitative reverse transcription-polymerase
      chain reaction (RT-PCR) followed by Southern blot analysis and localised by in
      situ hybridization. Densitometric data were analysed using Student's unpaired t
      test. Adjacent sections were also examined for iNOS protein expression by
      immunohistochemistry. RESULTS: Semi-quantitative RT-PCR/Southern analysis of RNA
      obtained from the 10 surgical specimens demonstrated that iNOS mRNA expression
      was significantly increased in the five nasal polyps (P < 0.05). In situ
      hybridization studies revealed strong iNOS mRNA signal localized to the
      respiratory epithelium of nasal polyps, but not nasal turbinates. This pattern
      was confirmed by immunohistochemistry. Localization to inflammatory cells or
      other subepithelial structures was not seen. CONCLUSIONS: We conclude that iNOS
      expression is upregulated in nasal polyp disease, and is localized to the polyp
      epithelial layer. These data reinforce the concept that the epithelial layer may
      be important in the pathogenesis of nasal disease, and suggest a potential role
      for NO in the formation of nasal polyps.

PMID- 9515596
TI  - Inflammatory mediators in naturally occurring rhinitis.
AB  - BACKGROUND: The mediators released during the allergic inflammatory reaction
      induce the clinical symptoms of the allergic disease and although there have been
      numerous studies investigating mediator release in allergen challenge models of
      allergic rhinitis very few have extended this approach to the study of natural
      disease. OBJECTIVE: The aim of this investigation was therefore to measure mast
      cell and eosinophil mediator levels and indices of vascular permeability in
      naturally occurring rhinitis. METHODS: Three groups of subjects were studied,
      normal non-rhinitics, seasonal allergic rhinitics in and out of the grass pollen
      season and perennial allergic rhinitics. Mediators were recovered using the
      technique of nasal lavage and the levels of tryptase, histamine, eosinophil
      cationic protein and albumin were determined. In addition, eosinophils were
      enumerated in nasal smears as an indices of underlying inflammation. RESULTS: The
      levels of tryptase, eosinophil cationic protein and albumin were significantly
      higher in the lavage recovered from the symptomatic seasonal allergic rhinitics
      than when asymptomatic (P = 0.05, P = 0.003, P = 0.009, respectively). These
      levels of eosinophil cationic protein and albumin were also significantly higher
      than those of the normal non-rhinitics (P = 0.0008, P = 0.0.003, respectively).
      In the perennial allergic rhinitics the levels of tryptase, eosinophil cationic
      protein and albumin were higher than the normal non-rhinitics (P < 0.0001, P =
      0.0003, P = 0.0001, respectively). The levels of tryptase and histamine were
      higher in the perennial allergic rhinitics than the seasonal allergic rhinitics
      (P = 0.0003, P = 0.006, respectively). These changes in mediator levels were
      accompanied by a significant influx of eosinophils into the nasal mucosa of both
      the symptomatic seasonal rhinitics, compared with asymptomatic (P = 0.04) and
      normal controls (P = 0.0006) and the perennial rhinitics compared to normal
      controls (P = 0.03). CONCLUSION: These results indicate that in both naturally
      occurring seasonal allergic rhinitis and perennial allergic rhinitis mast cell
      and eosinophil activation occurs and this is accompanied by an increase in
      vascular permeability. These measurements in lavage fluid provide a method of
      monitoring the mucosal cellular events in response to therapy.

PMID- 9515597
TI  - Neuropeptide innervation and neuroendocrine cells in allergic rhinitis and
      chronic hypertrophic rhinitis.
AB  - BACKGROUND: The neuropeptides and neuroendocrine cells are proven to exist in the
      human nasal mucosa. However, the pathophysiological and neuroimmunological roles
      of regulatory peptides in human nasal diseases require further investigation.
      OBJECTIVES: To investigate and compare the functional morphology and quantify the
      tissue concentration of regulatory peptides in the nasal mucosas of normal,
      allergic rhinitis (AR) and chronic hypertrophic rhinitis (CHR) subjects. METHODS:
      Human inferior turbinate mucosa specimens from 28 patients with AR, 25 patients
      with CHR and 15 patients without any nasal diseases were investigated. Using
      immunohistochemistry and radioimmunoassays, we detected the presence,
      distribution and concentrations of various neuropeptides (vasoactive intestinal
      peptides [VIP], neuropeptide Y [NPY], substance P [SP], calcitonin gene-related
      peptides [CGRP]) and general neuroendocrine markers (neurone-specific enolase,
      chromogranin A and somatostatin). Quantitative analysis of the stained fibres and
      cells were performed using a graphic AutoCAD program. RESULTS: The presence and
      distribution of NPY, CGRP, and SP nerve fibres and neuroendocrine cells were
      similar among the three subject groups. AR subjects had significantly higher VIP
      and SP tissue concentrations. VIP fibres had highest density in AR subjects and
      these fibers predominantly innervated vessels. In CHR, VIP fibres primarily
      innervated glands. CONCLUSIONS: VIP and SP may play an important
      neuroimmunological role in the pathogenesis of AR. VIP may lead to the
      hypertrophic changes of submucosal glands in the pathogenesis of CHR.

PMID- 9515598
TI  - Serum eosinophil cationic protein as a marker of eosinophilic inflammation in
      asthma.
AB  - BACKGROUND: The serum level of eosinophil cationic protein (ECP) has been used as
      a clinical marker in asthma, on the assumption that it reflects ongoing
      eosinophilic inflammation of the airways. However, only a few studies have
      investigated this issue, using bronchial secretions but not tissue specimens.
      OBJECTIVE: To evaluate cross-sectionally the correlation between serum ECP level
      or blood eosinophil count, and the degree of eosinophilia in bronchoalveolar
      lavage fluid (BALF) and bronchial biopsy tissue, and disease activity, in
      asthmatic patients. METHODS: Thirty-three adults with symptomatic asthma and six
      healthy controls were studied. The blood eosinophil count, ECP levels in serum
      and BALF, percentage of eosinophils in BALF, number of eosinophils in bronchial
      tissue, pulmonary function, and methacholine bronchial responsiveness of these
      subjects were clarified. An asthma severity score and inhaled beta2-agonist
      requirement (puffs/day) were also assessed for the asthmatic patients. RESULTS:
      The asthmatic patients, compared with the controls, had more obstructive (as
      tested by %FEV1, FEV1/FVC, and FEF25-75%) and more responsive airways, and showed
      a significant increase in the number of eosinophils in the blood, BALF, and
      tissue, and in the serum ECP levels. The ECP levels in BALF were below the
      detection limit for most of the subjects in both groups examined. In the
      asthmatic patients, serum ECP level demonstrated correlations with the number or
      percentage of eosinophils in BALF and tissue, whereas the blood eosinophil count
      correlated only with the percentage of eosinophils in BALF. Serum ECP level
      correlated with all indices of disease activity examined; %FEV1, FEV1/FVC, FEF25
      75% bronchial responsiveness, severity score and beta2-agonist usage, whereas the
      blood eosinophil count correlated only with %FEV1 and bronchial responsiveness.
      CONCLUSION: The data suggest that serum ECP level reflects the intensity of
      eosinophilic airway inflammation, as well as the disease activity, and may be
      useful as an inflammatory marker in asthma.

PMID- 9515599
TI  - Serum eosinophil cationic protein, eosinophil protein X and eosinophil peroxidase
      in relation to pulmonary function in cystic fibrosis.
AB  - BACKGROUND: Recently, increased serum levels of eosinophil cationic protein (ECP)
      in cystic fibrosis (CF) have been reported which were closely related to the
      levels in sputum. In the present study we investigated other eosinophil proteins
      such as eosinophil peroxidase (EPO) and eosinophil protein X (EPX) in sera of
      patients with CF and their relation to pulmonary function. METHODS: Serum samples
      from 42 patients with CF and from 25 healthy control subjects were measured for
      ECP, EPO and EPX. Lung function tests were performed by using whole body
      plethysmographic technique, and the results were correlated with the levels of
      eosinophil granule proteins. RESULTS: Serum ECP (median: 20.9 microg/L), EPO
      (median: 30.3 microg/L) and EPX (median: 37.9 microg/L) levels were significantly
      increased in CF compared with healthy controls (3.5 microg/L, P < 0.0001, 5.6
      microg/L, P < 0.0001 and 14.6 microg/L, P < 0.0001, respectively) whereas
      eosinophil counts were not different. There was a strong correlation between the
      levels of eosinophil proteins and variables of pulmonary function, like between
      ECP and forced vital capacity (r = -0.764, P < 0.0001). In addition, ECP
      concentrations were significantly related to the levels of EPO and EPX, albeit,
      in some patients with low ECP levels, increased EPO and EPX concentrations were
      observed. CONCLUSION: These results indicate that in patients with CF, ECP, EPO
      and EPX concentrations also were increased with a significant relationship
      between these three eosinophil proteins. Since eosinophil activity in patients
      with CF is strongly correlated with pulmonary function, the assessment of
      eosinophil granule proteins might be useful for clinical monitoring in CF.

PMID- 9515600
TI  - Evolution of lymphocyte transformation to wasp venom antigen during immunotherapy
      for wasp venom anaphylaxis.
AB  - BACKGROUND: Venom immunotherapy (VIT) has proven to be safe and effective in wasp
      venom anaphylaxis. However, there are no good parameters to indicate when to stop
      venom immunotherapy. OBJECTIVE: To evaluate the relationship of the lymphocyte
      transformation test (LTT) to history and specific IgE determination, and to
      address the time course of lymphocyte transformation responses to wasp (Vespula)
      venom during VIT and the possible utility of LTT to determine the duration of
      therapy. METHODS: Peripheral blood mononuclear cells (PBMCs) of 18 individuals
      with a history of wasp sting anaphylaxis and a positive serum-venom-specific IgE,
      were stimulated with wasp venom before immunotherapy, at the end of a 5-day semi
      rush immunotherapy and at 24 months during venom immunotherapy. Results,
      expressed as stimulation index (SI), were compared with the SI in seven
      asymptomatic stung controls. RESULTS: In controls the median (minimum-maximum) of
      the SI were 2.39 (0.52-3.39) before therapy and 2.39 (1.12-6.02) when repeated
      after 24 months. For patients the median (minimum-maximum) of the SI were 10.13
      (1.19-44.88) before immunotherapy (d0), 2.73 (0.67-12.03) at the end of the build
      up immunotherapy (d5) and 4.21 (0.88-14.66) at the end of 24 months of
      maintenance therapy (m24). The proliferation responses in vespid-allergic
      patients were significantly higher than in stung controls (P = 0.006) but only
      13/18 patients showed a positive LTT result before the start of immunotherapy
      (sensitivity of the LTT 72%). When the LTT was repeated after a 5 day build-up
      hyposensitization course the SI significantly dropped as compared to the pre
      treatment levels (P = 0.002). The SI of the LTT was negative in eight out of 18
      patients at 24 months and the median values were significantly lower than before
      therapy (P = 0.03). CONCLUSIONS: Although, in the absence of sting challenge data
      it is not possible to draw conclusions about the predictive value of the LTT, our
      data may suggest that abolition of the LTT during VIT might indicate clinical
      insensitivity. Further studies, comparing the results of sting challenges, with
      the results of lymphocyte transformation will be necessary in order to evaluate
      the role of LTT in stopping immunotherapy.

PMID- 9515601
TI  - Exploited carers at home.

PMID- 9515602
TI  - Women and midwives in partnership: a problematic relationship?
AB  - Midwives in New Zealand have been practising independently of medicine and
      nursing since 1990 using the concept of partnership as a basis for their
      practice. This article shows, however, that the beliefs which underpin the
      practice of the midwives are not always the same as those of their clients.
      Supporting evidence is provided in the form of verbatim data provided by
      participants. Three major areas in which contradictions were found were in the
      work of midwives, the knowledge for practice and reflections on the experience.
      It is recommended that midwives become more visible by removing themselves from
      hegemonic structures, valuing alternative forms of knowledge and respecting the
      knowledge of their clients.

PMID- 9515603
TI  - Privacy or help? The use of curtain positioning strategies within the maternity
      ward environment as a means of achieving and maintaining privacy, or as a form of
      signalling to peers and professionals in an attempt to seek information or
      support.
AB  - Midwives in the local maternity unit had noted that the interactions between
      women within the ward environment had started to decline. Women were spending
      long periods of time behind curtains drawn around their bed space. The staff
      hypothesized that this was because women desired the privacy of a single room.
      The literature review revealed a lack of understanding of the concept of privacy
      within a ward environment from a nursing or midwifery perspective. The review
      therefore, concentrated on the information offered by the fields of psychology
      and sociology. This study aimed to observe the methods women use to maintain or
      preserve their privacy within the ward environment. An ethnographic approach was
      used incorporating use of documentary evidence, participant observation and
      discussion, field maps and field notes. The findings of this study centred around
      the use of curtain positioning, subsequently referred to as 'signalling'. The
      strategies employed by women included complete closure for total withdrawal, semi
      closure for seeking information or support, and partial closure of curtains
      around the individual's bed space for periods of solitude or rest. The findings
      have implications for both general and maternity hospital wards but in
      particular, wards within maternity units that incorporate women with mixed
      methods of infant feeding, or women in labour mixed with either postnatal or
      antenatal women.

PMID- 9515605
TI  - Assessing strength of preference for abortion method using 'willingness to pay':
      a useful research technique for measuring values.
AB  - Policy makers and practitioners need to differentiate between patient preferences
      which are strongly held, and those which are not. This study measured not only
      women's preferences for medical abortion versus surgical vacuum aspiration, but
      also the strength of these preferences, using a 'willingness to pay' (WTP)
      technique. Fifty women were recruited and interviewed prior to and following
      termination of early pregnancy. Due to the sensitivity of the situation, the WTP
      approach was administered by interview. Results revealed that 34 (64%) preferred
      to have the medical method. The amounts offered for each method were similar;
      however, a minority gave higher values for the medical method, thus for those
      women their strength of preference for that method was more intense. Validity of
      the technique was supported by the finding of a positive association with social
      class and the importance women attached to having choice. It is argued that WTP
      is an acceptable method for the elicitation of strength of treatment preferences.
      Its further use by nurses and midwives to assess health care preferences should
      be explored, particularly when considering aspects of care which are
      traditionally difficult to identify and measure.

PMID- 9515604
TI  - Computers in midwifery practice: a view from the labour ward.
AB  - Concern continues to exist about the lack of integration of research into
      clinical practice. One of the reasons which has been suggested for this, is that
      practitioners may either not know about, or understand, the research findings.
      The availability of a database which contains systematic reviews of research such
      as the Cochrane Pregnancy and Childbirth Database, should go some way to overcome
      such obstacles associated with the implementation of research into practice. As
      part of a national audit on Caesarean section, a computer with the Cochrane
      Database was installed in the labour ward of each consultant maternity unit in
      Scotland. The purpose of this study was to determine if midwives working in
      labour wards make use of this accessible source of research findings to inform
      their practice. Anecdotal evidence suggested that although midwives were keen to
      use the databases, they did not have the requisite computer skills to do so. This
      study examined the computer literacy of midwives and their perceived educational
      needs. A questionnaire was distributed to all labour ward midwives in 22
      consultant maternity hospitals in Scotland (n = 850). This questionnaire
      considered issues such as the preparation of midwives to use computers, midwives'
      perceptions and use of computers and their perceived educational needs. The
      response rate was 74%. Following analysis of the questionnaire labour ward
      managers were interviewed by telephone to ascertain their views regarding the
      Cochrane Database and their perception of its effectiveness. The results
      highlighted that only 27% of midwives claimed to use the Cochrane Database on a
      regular basis. Overall midwives had a positive attitude towards information
      technology but claimed they did not have the requisite computer skills to use
      these tools. Managers agreed that there was a need for further instruction and
      support for midwives. The findings of this study have important implications for
      the future professional preparation and continuing education of midwives.

PMID- 9515606
TI  - Are children given insufficient pain-relieving medication postoperatively?
AB  - The literature often suggests and assumes that children are under-medicated
      postoperatively. A review of the literature leads to the conclusion that only a
      few studies answer the question of whether children's pain is relieved
      insufficiently. The lack of consensus on expected pain intensity after surgery
      and caution about prescribing analgesics could explain why analgesics are often
      prescribed on a pro re nata (prn) basis. Prescription on a prn basis, in fact,
      means that the nurse makes the decision whether or not an analgesic should be
      administered. Some studies suggest, however, that nurses under-medicate children
      and that postoperative pain is relieved insufficiently. In some situations,
      nurses under-estimate the child's pain, while in others, nurses' attitudes,
      beliefs and knowledge regarding pain relief strategies play an important role. On
      the basis of this review of the literature standard prescription of pain
      medication instead of prn is recommended. Furthermore, research on the incidence
      and prevalence of pain in children and on the effectiveness of analgesic
      administration postoperatively is warranted.

PMID- 9515607
TI  - In whose 'best interests'? Ethical issues involved in the moral dilemmas
      surrounding the removal of sexually abused adolescents from a community-based
      residential treatment unit to a locked, forensic adult psychiatric unit.
AB  - This study scrutinizes the ethical and moral dilemmas surrounding the removal of
      sexually abused adolescents from a community-based residential treatment unit to
      a locked, forensic adult psychiatric unit. Adolescent victims of sexual abuse
      exhibit a plethora of psychopathological symptomatology which can lead in many
      cases to the adolescent resorting to self-injurious behaviours in an attempt to
      relieve feelings of tension, anxiety and guilt. Because the unit in which the
      writer is involved is an open, community-based treatment centre with limited
      staffing levels, a completely secure environment may be compromised. Consequently
      self-injurious adolescents may become so disturbed that a more secure environment
      must be sought. The limited resources for disturbed adolescents in Northern
      Ireland means that occasionally the only option available to health care
      professionals who find themselves in this situation is to utilize the services of
      the psychiatric adult, forensic unit in Belfast which is contained within a large
      psychiatric hospital. Many would agree that such a placement for a disturbed
      adolescent seems inappropriate but is at the same time unavoidable. This study
      will examine the ethical and moral minefield that only recently has become a
      dilemma for health care professionals and particularly for nurses endeavouring to
      adhere to the code of professional conduct.

PMID- 9515608
TI  - Familial amyloidotic patients' experience of the disease and of liver
      transplantation.
AB  - Liver transplantation is a new treatment for familial amyloidotic polyneuropathy
      (FAP). No qualitative study examining these patients' experiences of the disease
      and the treatment has been published. The purpose of this study was to explore
      and describe the experience of the disease and the liver transplantation from the
      FAP patient's perspective. In-depth interviews with 11 liver transplant FAP
      patients were performed. The process of the FAP disease and a liver
      transplantation was found to involve the following categories: going downhill,
      defence and denial, a chance of surviving, the decision -- no choice, waiting
      powerless and uncertain, the first few steps after surgery, freed from the death
      sentence, still disabled, mastering up strength to recover, and the need for
      support and help.

PMID- 9515609
TI  - Postoperative variation in neurocognitive and functional status in elderly hip
      fracture patients.
AB  - Regaining independence in the performance of activities of daily living (ADL) is
      a nursing priority in the postoperative care of hip fracture patients, though
      often impeded by a temporary yet reversible decrease in cognitive status
      postoperatively. This study investigated the incidence and evolution of decreased
      cognitive status in geriatric hip fracture patients from admission through to the
      fifth postoperative day, and the relationship between cognitive abilities and
      functional (ADL) status. Twenty-six elderly hip fracture patients (f: 21, m: 5)
      with a mean age of 79.5 years (SD = 8.2) admitted to the emergency room of an
      academic medical centre were monitored longitudinally from admission until the
      fifth postoperative day regarding neurocognitive status and ADL status, as
      measured by the mini-mental state exam (MMSE; including subscales of memory,
      linguistic ability, concentration and psychomotor executive skills) and an
      adapted version of the Katz ADL-scale, respectively. Patients were categorized on
      the basis of cognitive status as follows: no cognitive impairment (MMSE > or =
      24), moderate (MMSE < or = 23 but > or = 18) and severe impairment (MMSE < or =
      17). Nineteen of the 26 patients (73.1%) showed cognitive impairment (MMSE < or =
      23) at some point in time before and/or after surgery. Some improvement in
      cognitive status was observed yet only selectively across patient cohorts and
      neurocognitive dimensions. Cognitive status, especially memorial ability and
      psychomotor executive skills, seemed to be most vulnerable to becoming impaired
      after hip fracture surgery. A relationship was found between cognitive and
      functional status, specifically, strong associations between memory and
      psychomotor skills relative to ADL and modest associations between linguistic
      ability and concentration relative to ADL. Further, patients with decreased
      cognitive status postoperatively remained more ADL-dependent than non-impaired
      patients. This study underscores the importance of a systematic assessment of the
      cognitive status of elderly hip fracture patients and linking these observations
      to functional ability in order to enhance the postoperative rehabilitation of
      this patient group.

PMID- 9515610
TI  - The experience of people awaiting coronary artery bypass graft surgery: the
      Icelandic experience.
AB  - Prolonged waiting for major elective surgery has been a problem in several
      Western countries for many years. In Iceland coronary artery bypass graft (CABG)
      surgery was installed in 1986 and this descriptive study was conducted to
      describe systematically the experience of Icelandic people waiting for CABG
      surgery with the purpose of gaining information about what nursing services these
      people need during the waiting period. The survey used a mailed questionnaire
      developed by the authors. The target population consisted of people awaiting
      coronary artery bypass graft surgery at the National University Hospital in
      Iceland, at two predetermined days with a 10-month interval. The return rate was
      81.8% (n = 72). Mean time on the waiting list was 5 to 6 months. The waiting for
      surgery had negative effects on the work and daily life of the majority of the
      subjects and they were dissatisfied with their health status. Prominent symptoms
      were fatigue, shortness of breath, chest pain, anxiety and depression. Most
      patients (86.6%) experienced stress with 28.4% of them reporting a serious level
      of stress. The majority reported considerable negative influences of their
      illness on their spouse and family, particularly on their emotional condition.
      The conclusion drawn is that shortening the waiting period for CABG surgery
      should be a primary objective; however, that may be unlikely with the present
      Icelandic health care system. Therefore, helping the individuals and their
      families live with the lengthy wait is a necessity.

PMID- 9515611
TI  - Difficulties in the measurement of outcome in people who have serious mental
      health problems.
AB  - In the present drive towards evidence-based health care it is essential for
      nurses to be able to define and measure their contribution in the health services
      and thereby ensure that resources are deployed to provide maximum improvement in
      the health of the population. Yet there exist few rigorous studies which examine
      the impact of the nursing contribution on patient health gain. One explanation
      for this is the sheer complexity of outcome measurement. This paper considers the
      multitude of factors which must be taken into account when designing studies to
      measure the impact of interventions for people with serious mental health
      problems. The heterogeneous nature of the population, the range of services these
      people might use, the composite of possible interventions and the paucity of
      adequate measurement tools are among the issues to be tackled. Although no single
      methodology can be prescribed, a number of principles are offered to guide study
      design.

PMID- 9515612
TI  - The knowledge and attitudes of mental health nurses to electro-convulsive
      therapy.
AB  - Three hundred and forty-five questionnaires containing the knowledge and attitude
      scale for ECT devised by Janicak et al. (1985) were distributed to mental health
      nurses working in Wales, the data were collected from the 167 returned.
      Limitations in the reliability of the instrument with respect to the degree of
      internal consistency were found, this suggested that the knowledge statements
      used were inconsistent in providing a reliable measure of respondents knowledge
      of ECT. Findings suggested that a higher level of knowledge appeared to be
      associated with the length of experience of the nurse and their area of clinical
      practice. In addition, there were substantial variations in actual knowledge,
      particularly with regard to cognitive side-effects with ECT. Attitudes to ECT in
      this study were significantly related to the place in which the nurse was
      practising and the degree of contact the nurse had with patients receiving the
      treatment. Greater knowledge scores were obtained by those nurses who indicated a
      more positive response towards ECT. The conclusions suggest that knowledge of ECT
      required improvement in many cases, and this has implications for nurse
      education. A relationship between knowledge and attitudes appears to exist in
      this study, however, such a relationship would need to be tested further in
      future research.

PMID- 9515613
TI  - Consensus guidelines for the promotion and management of continence by primary
      health care teams: development, implementation and evaluation. NHS Executive
      Nursing Directorate.
AB  - A project was undertaken as part of the NHS Executive Strategy for Major Clinical
      Guidelines, involving the development of national clinical guidelines for the
      promotion and management of continence by primary health care teams, through the
      process of managed consensus based on scientific review. The guidelines were then
      implemented at one urban general practice. This article outlines the development
      and implementation of the guidelines and describes the study undertaken to
      evaluate the impact of implementation on clinical outcomes. The study involved a
      pre-and post-implementation postal survey of a random sample of 17% of patients
      aged 18 years and over from the practice (n = 1503). The pre-implementation
      survey determined the period prevalence of incontinence, related biological data
      and data on the pre-implementation management of incontinence. Incontinence
      sufferers were invited to have their condition assessed or reviewed. All
      sufferers who agreed to be followed-up were sent the post-implementation survey,
      which identified those patients who had sought help, and ascertained reasons for
      not seeking help. Data on the management of incontinence post-implementation were
      also obtained. Clinical outcomes measured pre- and post-implementation were a
      validated severity index for urinary incontinence, (also adapted for faecal
      incontinence) and perception of the incontinence as a problem. A 3-month period
      was allowed between pre- and post-implementation surveys. The study confirmed
      previous research which showed that few incontinence sufferers respond to
      invitations to seek help, and that help-seeking behaviour was significantly
      related to severity of incontinence. The guidelines did not have any positive
      impact on the clinical outcomes measured, although slight improvements in
      approaches taken by the primary health care team to the promotion and management
      of continence were recorded. However, the study was limited by the small sample
      size and short time scale. Further evaluation of the impact of the guidelines on
      these outcomes is therefore recommended.

PMID- 9515614
TI  - Implementing health promoting nursing: the integration of interpersonal skills
      and health promotion.
AB  - Health promoting nursing practice is seen as the way forward for the nursing
      profession. This paper outlines the meaning of health promotion and distinguishes
      between a traditional and new paradigm approach. The research examining the
      extent to which a new paradigm approach is practised demonstrates that, to date,
      nurses predominantly adopt the traditional approach to health promotion. It is
      argued that the integration of interpersonal skills and health promotion within
      nursing curricula is crucial in enabling the transfer of theoretical concepts
      into practice. The ways in which this integration has been approached within one
      college of nursing are described. The difficulties encountered in attempting this
      integration and accomplishing a philosophical shift from a traditional to a new
      paradigm approach to health promotion are discussed and critiqued. Specifically
      conflicts that occur at an interpersonal, organizational and societal level are
      identified and proposed as explanations for the slow implementation of health
      promoting nursing.

PMID- 9515615
TI  - Clinical leadership in nursing development units.
AB  - There is an expectation for Nursing Development Units (NDUs) to explore and
      develop the clinical leadership role. This paper describes how 28 Department of
      Health funded NDUs in England sought to meet this objective. We describe the
      personal and professional characteristics of NDU clinical leaders (CLs) and their
      perceived responsibilities. We identify 10 elements which appear to be central to
      the CL role and together form a core role set of the leader which is applicable,
      to some extent, across clinical specialties and settings. The position of the CL
      in the organizational hierarchy emerges as crucial to his/her ability to act on
      these responsibilities and fulfil a leadership role.

PMID- 9515616
TI  - A triangulation approach to the identification of acute sector nurses' training
      needs for formal nurse practitioner status.
AB  - The current confusion surrounding the definition and role function of the nurse
      practitioner (NP) has created a situation in which advanced clinical practice is
      delivered in a variety of ways and at many levels. Not surprisingly, this has led
      to difficulties in regulating educational provision for NPs. This study reports a
      survey of the perceptions of the role definitions and training needs of all
      nurses working at advanced clinical levels within an acute sector Trust. Although
      this concept is not a novel one in advanced nursing practice, the procedure
      adopted differed from previous studies in two fundamental ways: firstly, a unique
      training needs assessment instrument was used, which because of its validity and
      opacity, was capable of yielding a highly reliable data-base, comprising a
      prioritized profile of real training needs as opposed to the standard wish-list
      typically elicited. Secondly, it did not rely simply on the self-reported needs
      of the nurse sample, but also included the perceptions of the sample's immediate
      medical and managerial colleagues. In this way, a triangulation paradigm was
      adopted. The results indicated that overall, there was high agreement between the
      nurses and their managers, regarding both the definition of the NP role and the
      essential training requirements, with somewhat different opinions being offered
      by the medical staff. When the raw scores were standardized to correct for
      response bias, the data provided an operational definition of the role of the NP
      and a prioritized profile of training needs for nurses who wished to train to
      this level.

PMID- 9515617
TI  - Using the 'new' statistics in nursing research.
AB  - This paper argues that quantitative methods are under-used in nursing research.
      Although this is often because the qualitative approach is the most appropriate,
      it may also be because nurse researchers are not fully aware of modern,
      sophisticated data analysis techniques and have tended to use simple statistical
      techniques that often make the quantitative analysis of complex data very
      difficult and produce simplistic and unsatisfactory answers. The paper briefly
      discusses probability and survival modelling techniques suitable for use in
      complex nursing research situations and argues that these methods may help to
      bridge the qualitative-quantitative gap. Although these techniques are
      mathematically complex, they are easily applied in practice using dedicated
      computer programs. The paper describes their application using one such program,
      GLIM 4.

PMID- 9515618
TI  - The quality of assessment of patients with chest pain: the development of a
      questionnaire to audit the nursing assessment record of patients with chest pain.
AB  - The quality of nursing and medical records has been a source of concern for many
      years (Audit Commission 1995). This study has two main purposes: firstly, to
      design an audit questionnaire to evaluate the quality of nursing assessment
      records of patients with chest pain; and secondly, to make some tentative
      conclusions about the quality of nursing assessment of patients with a chest pain
      in order to pinpoint areas that need further study. A sample of 30 patients was
      selected for this study on the basis of some well-defined inclusion criteria. The
      nursing assessment notes of these patients were evaluated using the audit
      questionnaire. It was found that the questionnaire was effective in gleaning
      appropriate information from the nursing notes to be able to derive some
      tentative conclusions about the quality of nursing assessment of patients with
      chest pain, i.e., on the whole nursing assessment was found to be superficially
      carried out, potentially making errors of omission and commission likely to
      occur. The inter-rater reliability of the questionnaire was found to be good. The
      questionnaire also seems to measure what it purports to measure (i.e. has content
      validity). However, this needs to be further checked by using a larger sample.

PMID- 9515619
TI  - Alertness to the needs of others: a study of the emotional labour of caring.
AB  - This study attempts to recognize and value emotional labour and the skills
      involved and embodied within it. Also, there is an attempt to deliberately re
      value the caring component of nursing. Caring is identified as the central task
      of the nurse, emotional labour is part of caring and therefore a defence of
      emotional labour is central to affirming nursing's worth. The study draws on the
      work of Hochschild who first used the term emotional labour to define the
      undefined, unexplained component of the work mainly carried out by women. Such
      caring work also is not officially recorded and may only be passed on in an oral
      tradition. Case studies of three experienced enrolled nurses (level 2) who were
      on a course to convert their nursing qualification to registered nurse (level 1)
      were compiled. Phenomenology as an inductive, descriptive research method was
      used to investigate and describe their experiences as emotion managers at home
      and emotion workers in clinical hospital settings. From the case studies, it was
      concluded that all three women recognize emotion work as work but also that this
      type of work is not recorded. They also were not able to name skills used for
      such work and generally believe that it is through life experience that they have
      learnt emotion management. I used the information from my conversations with the
      women to name skills, indeed the title of the study is one such skill. All three
      women demonstrated a positive self-evaluation of their work although they felt
      that society did not value care work. I use some of their comments, the
      literature and my own thoughts to discuss ways of improving and valuing the
      emotional labour of nursing.

PMID- 9515620
TI  - Development through self-assessment: strategies used during clinical nursing
      placements.
AB  - The question asked for this small research project was 'how do senior students
      judge their progress towards being a "good nurse"?' A qualitative approach was
      taken and a convenience sample of 10 student midwives identified. Interviews were
      the main source of data collection. Since the method of analysis was that of
      grounded theory, the interviews became more focused as themes emerged. Results
      demonstrated that each student developed a range of self-assessment strategies
      which were used in any clinical placement. Some techniques were used only at a
      certain stage in a clinical placement while others were used throughout. Cyclical
      techniques were related to the achievement of short-term goals; strategies used
      for the duration of the placement had more long-term significance. Highlights of
      the findings were explored in the literature. These features included models of
      professional development, the need to feel part of a team, the necessity of
      identifying a role model, and the significance of the length of a clinical
      placement. Conclusions related to the duration of a clinical placement and the
      necessity for the student to have the opportunity to complete the cycle. The
      value of acquainting new students with self-assessment strategies is suggested.

PMID- 9515621
TI  - Reflection and nursing education.
AB  - The notion of reflection has become a significant concept within nursing
      education. What is it? How is it learned/taught? How is it implemented in
      practice? This paper explores reflection as both a technique and a purposeful
      inter-subjective process. Some of the current theoretical underpinnings of
      reflection, with particular attention to a Heideggerian perspective, are
      examined. It is suggested that the Heideggerian notion of reflection as the
      integration of calculative and contemplative thinking is an effective way to
      consider the concept of reflection.

PMID- 9515622
TI  - Absorption of nursing students: new immigrants in the general academic nursing
      programme in Israel.
AB  - Two years after upgrading its nursing programme to university level, Israel
      experienced a massive wave of immigration from the former Soviet Union. Previous
      studies have shown that Russian immigrants in general, and in nursing in
      particular, have several unique characteristics that need to be taken into
      consideration in planning curricula and absorption programmes. The aim of the
      present work was to update these data, focusing on the reasons new immigrants
      choose nursing as a career, their image of the profession and their satisfaction
      with it. The study population consisted of 302 students attending five major
      academic schools of nursing in Israel. Students were divided into two groups: new
      immigrants (less than 4 years in Israel) and long-time Israelis (more than 4
      years in Israel). All completed a 30-item questionnaire of proven validity and
      reliability. Findings were analysed by length of time in Israel and year of
      study. Using a series of statistical tests, we found that compared with the long
      time Israelis, the new immigrants came from a higher socio-economic/professional
      stratum (in their mother country), had a less 'technical' perception of nursing,
      and were attracted to the profession primarily for extrinsic reasons ('close to
      medicine', economics). Both groups showed highest satisfaction in the clinical
      domain; however, the difference was significant only in the long-time Israeli
      group, even though the new immigrants had rated this domain highest in
      importance. The new immigrants showed least satisfaction in the academic domain.
      These results could be explained by several factors: the financial and housing
      problems that accompany immigration; the higher proportion of married students in
      the new immigrant group; and especially language difficulties, which are
      multiplied in Israel, where mastery in both Hebrew and English is necessary. Of
      particular interest was the fact that many of the immigrant students had already
      begun or completed medical school in their old country but were forced to
      compromise their dreams on immigration. This affected both their image of nursing
      and their reasons for choosing it as a career. We believe these findings will
      help nurse educators identify areas in which they can help ease the absorption
      process for maximal benefit to both the students and the profession.

PMID- 9515623
TI  - Qualified nurse smokers' attitudes towards a hospital smoking ban and its
      influence on their smoking behaviour.
AB  - This study explored the effects of a complete smoking ban in a large British
      teaching hospital on nurses' smoking behaviour and their attitudes and views on
      the current policy and compliance with it. Questionnaires were distributed to a
      convenience sample of nurse smokers and ex-smokers 9 months after the
      introduction of the smoking ban. A response rate of 64.7% (n = 33) was achieved.
      The reported reduction in work-time cigarette consumption following the ban was
      not statistically significant (Wilcoxon test: P = 0.069). No reduction outside
      work was recorded. Six (21.4%) smokers claimed that the ban had been a reason for
      them to try to give up smoking. Two of three ex-smokers reported that the ban had
      played a role in their giving up. The respondents showed considerable agreement
      with their health educator and role model function. Support for the policy was,
      however, very limited and compliance with it was reported to be poor among
      patients as well as staff. Twenty (76.9%) of current smokers indicated their wish
      to give up, 11 (39.3%) of them believed their own determination to be an
      effective way to achieve this. These results would seem to indicate that smoking
      policies currently have limited impact on smoking behaviour. It is suggested that
      in future policies should aim at strengthening nurses' determination to give up
      as well as secure their support for the restrictions in order to assist them in
      changing their smoking behaviour.

PMID- 9515624
TI  - Ritual action and its effect on the role of the nurse as advocate.
AB  - Problems related to the ability of the nurse to act as advocate for patients have
      caused dilemmas in the profession over recent years. This paper seeks to address
      the issue from the aspect of ritual action which pervades the day-to-day
      activities of nurses and could therefore have an effect on nurse-patient
      relations. By looking at a short study based on data from nurses working with
      dying patients, part of work in progress on the subject, it is possible to draw
      some conclusions about the effect that such rituals and routines have on
      practice. Examination of the work of Douglas leads to speculation about the ways
      that rituals associated with restricted language can undermine the nurse's
      ability to advocate successfully. Results from the study are limited given the
      small sample, but they give some indication of trends and possibilities that more
      exhaustive research may confirm.

PMID- 9515625
TI  - Nurses' responses to people with schizophrenia.
AB  - General nurses, psychiatric nurses and lay people were investigated to identify
      differences between their personal standards concerning how they should respond,
      and beliefs about how they actually would respond, towards the target group,
      'people with schizophrenia', in each of three response domains (thinking, feeling
      and behaving). Significant differences were identified between the response types
      and between the different response domains. Significant interaction effects were
      also identified based on participants professional status in nursing. It is
      argued that the results support Devine's (1989) theory concerning the automatic
      activation of stereotypes and their controlled inhibition in favour of different
      personal beliefs. It is also argued that professional specialization in
      psychiatric nursing facilitates this process in relation to the target group.

PMID- 9515626
TI  - Preconditions for and consequences of self-determination: the psychiatric
      patient's point of view.
AB  - In the context of an interview study concerned with self-determination in
      psychiatric patients, this paper describes the preconditions for and consequences
      of self-determination from the point of view of psychiatric patients themselves.
      The data were collected in semi-structured interviews with long-term psychiatric
      patients (n = 72) and analysed using the method of content analysis. Responses on
      the preconditions for self-determination were grouped into three categories:
      firstly, there were those who said that reference to self-determination in the
      case of psychiatric patients is nonsense; secondly, there were those who said
      that self-determination requires no preconditions; and thirdly, there were those
      who said that there are certain preconditions, such as the ability to think and
      make decisions, activity, obedience, and illness. Both positive and negative
      consequences were identified in situations where self-determination is
      maintained, but only negative consequences in situations where self-determination
      is lost. On the basis of these tentative results, self-determination seemed to be
      relevant in psychiatric nursing. We are continuing to develop and test an
      instrument for the evaluation of the opportunity for self-determination in
      clinical practice.

PMID- 9515627
TI  - The problem drinker's lived experience of suffering: an exploration using
      hermeneutic phenomenology.
AB  - Research in the area of problem drinking has traditionally relied on quantitative
      methodologies which view the problem from the researcher's perspective. The
      purpose of this hermeneutic-phenomenological study was to describe and understand
      the problem drinker's lived experience of suffering using a philosophy and
      research approach which preserves the uniqueness of the experience from the
      sufferer's point of view. The method involved conducting in-depth interviews with
      a sample of six problem drinkers. Interviews were analysed using an interpretive
      process, which aimed at generating a deeper understanding of the topic by
      facilitating a fusion of the world views of both participant and researcher. A
      reflexive journal recorded the involvement of the self of the researcher
      throughout the research process. Suffering was viewed as a spiralling vicious
      circle of physical, psychological, social and spiritual distress. Symptoms of
      physical dependence, shame and guilt emerged strongly as being both sequelae of
      heavy drinking and cues to further drinking bouts. Evoking memories of previous
      suffering through telling one's story was found to be an empowering and
      motivating force. The results have relevance to specialist and generic workers,
      who are urged to pay greater attention to the social, psychological and spiritual
      care of problem drinkers.

PMID- 9515628
TI  - Exploring evidence based practice: international conference organized by the
      University of Southampton School of Nursing and Midwifery at the Chilworth Manor
      Conference Centre, Southampton, England, 12-14 September 1997.

PMID- 9515629
TI  - Re:Conference report--Clinical Nurse Specialism Conference organised by
      Professional Nurse, November 1996, reported in Journal of Advanced Nursing 1997,
      25, 867-870.

PMID- 9515630
TI  - Therapeutic touch.

PMID- 9515631
TI  - On being a patient.

PMID- 9515632
TI  - Caring for demented people in their homes or in sheltered accommodation as
      reflected on by home-care staff during clinical supervision sessions.
AB  - This study aimed to illuminate both the content of and the care given to demented
      people and the reflections of home care staff about it as revealed in two
      clinical group supervision sessions (n = 36). Verbatim transcriptions were
      analysed using a phenomenological hermeneutic approach and the following were
      found to be reflected on: the pensioners' personal situation--disease-related
      behaviour, ADL-functions, social network and self-esteem; the pensioners'
      environment--their relationships to significant others, adequate level of
      housing/care, access to activities, and satisfactory personal space;
      pensioner/staff interaction--their relations to each other, the staffs' relation
      to the pensioners' family, and the balance between reality-orientation vs.
      validation; the staff's situation--co-operation with other professionals, in
      primary health care, hospital, and within the social services; job satisfaction,
      lack of knowledge and sharing of knowledge, and lack of resources, especially
      time. The reasoning of the participants under supervision was found to be based
      on medical, historical, psychological, and environmental explanations, or
      personal beliefs. Feelings explored during supervision were directed towards the
      pensioners or the pensioners' families, towards themselves or towards the
      management. The findings were interpreted within a nursing model based on the
      four central concepts of nursing; person, environment, nursing intervention and
      health. The reasoning about nursing care revealed in the supervision sessions
      reflected a holistic approach and the relationship between the staff and the
      demented person stood out as central for care quality. Thus focusing on what
      promotes or, respectively, obstructs this relationship is likely to be one
      important focus in clinical supervision not only to achieve improvement and high
      quality in home care but also to develop and enhance the quality of the working
      life of the staff. Since the results could be understood within a theoretical
      nursing care model, it may well be that if the supervisor functions within some
      theoretical model the participants may reach a more conscious approach and the
      risk of losing important aspects of caring will decrease.

PMID- 9515633
TI  - The clinical skills of community psychiatric nurses working with patients who
      have severe and enduring mental health problems: an empirical analysis.
AB  - This study describes the use of reliable scales to rate the clinical skills of
      mental health nurses when working with individuals and families with severe
      mental health problems. The Cognitive Therapy Scale and the Schizophrenia Family
      Work Scale were adapted for the study and were shown to have good inter-rater
      reliability when assessing audio-taped interviews carried out by mental health
      nurses during their usual course of work with patients with severe mental health
      problems and their families. The sample of mental health nurses studied were
      shown to have significantly better general therapy skills than specific cognitive
      therapy technical skills. The implications for training are discussed.

PMID- 9515634
TI  - Parents' viewpoint on reproductive health and contraceptive practice among
      sexually active adolescents in the Port Harcourt local government area of Rivers
      State, Nigeria.
AB  - The viewpoint of parents on reproductive health, specifically their attitude
      towards contraceptive use among sexually active adolescent daughters and general
      opinion on adolescent pregnancy, was examined. A sample survey of parents of
      pregnant adolescents in Port Harcourt was conducted. A greater proportion (79.1%)
      of parents did not favour the use of contraceptives by sexually active
      adolescents because according to their parents, contraception kills. Also, most
      (87.8%) parents did not usually discuss sexual matters with their adolescent
      girls. However, the majority (93.2%) of parents would want a sex education
      programme in schools in order to prevent unwanted pregnancy.

PMID- 9515635
TI  - Educational intervention with international nurses and changes in knowledge,
      attitudes and willingness to provide care to patients with HIV/AIDS.
AB  - This paper reports the findings of a study which examines the relationship
      between the use of an educational intervention with nurses from several Asian
      countries and changes in knowledge, attitudes and willingness to care for
      patients with human immunodeficiency virus/acquired immunodeficiency syndrome
      (HIV/AIDS). A pre-test and post-test questionnaire was used to collect the data.
      The results indicate, that whilst there was an improvement in knowledge following
      the educational intervention, there is a need for further improvement in the
      knowledge levels of the nurses. The method of contracting the virus is less
      influential in shaping students' attitudes towards people with HIV/AIDS. Fear of
      contagion is evident; this increases when more invasive clinical procedures are
      being carried out. What is also evident is that multiple levels of infection
      control protocols are used with patients. Fear of contagion is also apparent in
      the participants' willingness to work with colleagues and patients with HIV/AIDS.
      While the participants stated that they were more willing to work with colleagues
      and patients with HIV/AIDS following the educational intervention, they said that
      they would continue to take additional precautions for fear of contracting HIV in
      the workplace. The conclusion emphasizes that it is important for education about
      HIV/AIDS to be incorporated within current undergraduate and in-service
      programmes.

PMID- 9515636
TI  - Lecturer practitioners: a literature review.
AB  - Much of the existing literature on lecturer practitioners to date is comprised of
      the perspectives of individuals within the role and how they function in their
      specific setting. It is surprisingly difficult from this work, however, to define
      the role of lecturer practitioner. The authors were commissioned by a regional
      health authority to undertake a study of lecturer practitioners within that
      region. In the process of undertaking this study, a literature review was carried
      out. Whilst the authors found an abundance of literature surrounding the theory
      and practice gap, and the development of the lecturer practitioner role as one
      possible solution, they were not able to find a comprehensive review of the
      multifaceted aspects of the lecturer practitioner role. This paper is an attempt
      to provide such a review, and will address the following aspects: the need for
      lecturer practitioners; their origin within nursing and midwifery education; the
      development of the lecturer practitioner role; the debate surrounding academic
      and clinical credibility; and finally, the current situation for lecturer
      practitioners.

PMID- 9515638
TI  - The philosophy and physics of holistic health care: spiritual healing as a
      workable interpretation.
AB  - Holism is spoken of frequently in the nursing and medical press, linked with
      alternative or complementary practices, but on examination appears to have much
      greater depth. There would appear to be many interpretations of the term, many of
      which are not made explicit within an article. Holistic health care can only be
      interpreted in relation to an individual's perception of holism. This discussion
      asks that thought be given to what we perceive as reality, and where 'whole'
      begins and/or ends, using a brief, simple review of quantum theory as the basis
      for the discussion. The concept of spiritual healing, without any religious
      basis, is introduced in support of a personal interpretation of holistic care.

PMID- 9515637
TI  - The treatment of pressure sores: a comparison of novice and expert nurses'
      knowledge, information use and decision accuracy.
AB  - The knowledge experts have and the way it is organized is thought to affect their
      decision accuracy and the information they use to make decisions. This
      exploratory study examines the information used by experts, the way they organize
      their knowledge and their decision accuracy when considering treatments for
      pressure sores. A convenience sample of 14 subjects (seven experts and seven
      novices) were given a card sorting task and a decision task. The cards for the
      sort contained photographs of pressure sores and various dressings, which the
      subjects had to place into meaningful categories. In the decision task they were
      given a photograph of a pressure sore, together with various items of information
      which could be used to make a decision about the appropriate treatment for the
      pressure sore. The accuracy of the subjects' decisions were compared to a 'gold
      standard' decision formulated by an expert panel. Results indicated that experts
      were more accurate in their choice of treatments in the decision task, and also
      focused on specific items of information to make their decisions. The accuracy of
      their decisions was not linked to the categorization strategy used in the card
      sorts. The findings from this study indicate that more research into the way in
      which such treatment decisions are undertaken needs to be carried out.
      Specifically, the way in which education into wound care treatments affects
      decision accuracy needs to be identified, and ways of aiding individuals to focus
      on relevant information explored.

PMID- 9515639
TI  - The concept of spirituality in nursing theories: differing world-views and extent
      of focus.
AB  - Although nursing has recognized spirituality as an important aspect of holistic
      patient care, exactly what spirituality means has remained rather amorphous. The
      purpose of this article is to present aspects of spirituality found in modern
      nurse theorists' ideas. These aspects are presented both in relation to
      reciprocal interaction or simultaneous action world-views and in relation to the
      extent of focus on the concept within the model or theory. This discussion will
      provide the researcher and practitioner with additional theoretical understanding
      on which to ground investigations and base practice.

PMID- 9515640
TI  - Non-compliance and professional power.
AB  - The non-compliance of patients with prescribed treatments is considered as a
      barrier to effective health care. Non-compliance has implications for the health
      of patients, effective use of resources and assessments of the clinical efficacy
      of treatments. Research into non-compliance has increased over the last 30 years.
      This seems to indicate that it is seen as an important area of concern for all
      health care professionals. Definitions of non-compliance are problematic, as are
      methods of assessment of its nature and frequency. Many factors which may account
      for non-compliance have been proposed, as well as methods to improve compliance.
      Research into these factors however, mainly based on a positivist epistemology,
      has failed to provide any conclusive answers to the problem. Sound clinical
      reasons are suggested as the basis for the increase in interest in non
      compliance. It is contended, however, that it is not only these reasons that
      account for the identification of non-compliance as a problem. Non-compliant
      behaviour is seen as problematic, because it contravenes professional beliefs,
      norms and expectations regarding the 'proper' roles of patients and
      professionals. These have formed the basis of an ideology that views patients as
      passive recipients of health care. It has led to an inherent tendency to 'blame'
      the patient and view non-compliance as irrational and deviant. The professional
      view of non-compliance as irrational, is exemplified in the case of individuals
      with mental illness, where there are inherent assumptions that non-compliance can
      be seen primarily as a symptom of illness. This denies the legitimacy of patient
      choice, and has led to attempts to control compliance via suggested legislative
      measures. Serious moral and ethical problems arise from such measures, and can be
      seen as the ultimate legitimization of an ideology of non-compliance. The
      maintenance of professional power and control is suggested as central to the
      debates surrounding non-compliance. The ideological assumptions underpinning the
      concept of non-compliance need questioning, and a re-conceptualization of the
      roles of patients and professionals is required. This must involve a view of
      patients as active participators in their own health care. Research based on an
      interpretative epistemology, aimed at understanding individual action, rather
      than control, would seem a more appropriate model to pursue.

PMID- 9515641
TI  - Coping strategies and quality of life among patients on continuous ambulatory
      peritoneal dialysis (CAPD).
AB  - The present study describes CAPD patients' coping strategies and quality of life.
      A descriptive-comparative design was chosen and a consecutive series of patients
      (n = 26) was included. Data collection was performed through questionnaire and
      interview. Coping was measured by the Jalowiec Coping Scale and quality of life
      by the Swedish Health-Related Quality of Life Survey (SWED-QUAL). The main
      results show that an optimistic coping style was the most widely used by both men
      and women and this style was also considered to be the most effective in terms of
      dealing with stressful treatment aspects. Significantly more men than women found
      emotive coping to be less effective. Compared to a sample from the general
      population, CAPD patients had lower values on all SWED-QUAL sub-scales except
      those that tapped family functioning and emotional health. In general, women
      evidenced a more negative perception of their health than did men. With respect
      to emotional well-being/negative aspect, the CAPD patients achieved higher scores
      than the general population. The findings suggest targets for nurse
      practitioners' provision of support and information and in assisting patients to
      better utilize adequate coping methods to enhance their quality of life.

PMID- 9515642
TI  - Predictors of psychological distress in chronic pain patients.
AB  - The purpose of this study was to identify sources of psychological distress in
      patients attending pain clinics. Patients attending two pain clinics in the UK
      completed a self-report assessment questionnaire which included a 12-item, 5
      point semantic differential measure of psychological well-being/distress,
      together with a range of single-item measures of pain and psychosocial factors
      measured using 5-point verbal report scales. Multiple regression analysis
      identified that 60% of the variance associated with psychological distress was
      explained by a combination of fears about the future, regrets about the past, age
      (younger people were more distressed), practical help (more help was associated
      with more distress), feeling unoccupied and personal relationship problems. These
      results support previous findings which have suggested that a significant
      proportion of the emotional disturbance in chronic pain patients is associated
      with psychosocial factors which are either secondary to, or concurrent with, the
      pain. The method described provides a simple and quick method of assessment which
      may be used by nurses in clinical settings to identify sources of psychological
      distress in patients with chronic pain and opportunities for therapeutic
      intervention.

PMID- 9515643
TI  - Smoking habits among Finnish middle-aged men: experiences and attitudes.
AB  - The purpose of this study was to explain smoking habits amongst middle-aged men
      in Finland by describing their experiences of smoking and their attitudes towards
      smoking. As a pilot survey for a major health campaign targeted at 40-year-old
      men, the data for this study were collected using two questionnaires in
      connection with voluntary medical examinations. The first questionnaire was based
      on Prochaska's theory of stages of change in health behaviour. The second
      instrument was an attitude scale developed specifically for this study on the
      basis of Green and Kreuter's theory of factors influencing health behaviour.
      According to the results 31% of males aged 40 were regular smokers. Men with a
      lower level of education and out of work smoked more often than others. Non
      smokers reported a better self-perceived health than smokers. Smoking cessation
      is a process in which men gradually proceed from one step to the next. In this
      study 12% of the men were in the contemplation stage and 11% in the preparation
      stage. One-quarter of the men had recently given up the habit and were in the
      action stage, while 2% had quit smoking over 6 months ago and were in the
      maintenance stage. One-quarter of the men regarded smoking as an integral part of
      their way of life and felt that public opinion towards smoking is hostile.

PMID- 9515644
TI  - A comparison of the effects of patients' pain on nurses working in burns and
      neonatal intensive care units.
AB  - Nurses are more likely than other health professionals to be exposed to
      individuals who suffer severe pain for extended periods of time. Such exposure is
      likely to arouse emotional distress which not only has implications for their
      occupational health but may interfere with their ability to manage pain
      effectively. This study compared the emotional reactions to their patients' pain,
      of nurses who were exposed to patients with severe and obvious pain (nurses
      working in burns units) and nurses whose patients' pain is uncertain because they
      are unable to communicate (nurses working in neonatal intensive care units). The
      results showed that pain generated greater anxiety in nurses caring for patients
      with severe burns, but that they also demonstrated a greater sense of personal
      competence and control over the management of their patients' pain. The findings
      also showed that when dealing with patients' pain the morale of nurses was linked
      to: (a) perceived challenges to their images of themselves as alleviators of
      pain; (b) the extent to which their sense of personal vulnerability was aroused
      by contact with patients experiencing severe pain; (c) their beliefs about their
      ability to assess patients' pain; and (d) the quality of their professional
      relationships with the medical staff who controlled the most powerful forms of
      pain relief.

PMID- 9515645
TI  - An ethnographic study of the process of medication discharge education (MDE).
AB  - (MDE) Medication discharge education (MDE) is an essential component of the
      hospital discharge process. It is especially important for older persons with
      heart disease because they are among the highest users of hospital care. Accurate
      management of medications is believed to be one strategy to prevent or delay
      hospitalization. Despite its accepted importance, there is little documented
      research about patient education in general, or MDE in particular. This
      ethnographic study collected interview, observational, and document data from
      older persons with heart disease, family members, nurses and medical records in
      order to describe the process of MDE. MDE was found to be both structured and
      unstructured, uncoordinated, and driven by accreditation guidelines. Older
      patients and their family members valued MDE, especially when information was
      personalized, provided orally and reinforced in writing. Suggestions for
      improving the effectiveness of MDE are offered.

PMID- 9515646
TI  - Nurses' responses to severity dependent errors: a study of the causal
      attributions made by nurses following an error.
AB  - Attribution theory attempts to understand how people explain events and their own
      role in them, particularly events which are unusual or unpleasant. Based on
      previous studies on attributions, it was suggested that nurses would make more
      external attributions (i.e. blaming others or the environment) following an error
      with a serious outcome than one with a non-serious outcome. This would in turn
      suggest that they might be less likely to respond constructively and learn from
      serious errors. Sixty nurses were approached for this study. They were divided
      into two groups. One group (30 subjects) completed a questionnaire on the
      responses to a description of an error with a non-serious outcome and the second
      group (also 30 subjects) responded to questions to an identical error but with a
      serious outcome. The findings from this study indicated that nurses behaved in an
      atypical manner in response to making an error. Although both groups of nurses
      tended to make slightly more internal attributions for the error, indicating that
      they are likely to take responsibility for their error, those nurses in the
      serious outcome condition blamed themselves more for the error. This may be due
      to the strong professional ethos which exists amongst nurses that expects them to
      take responsibility for their actions. This would inevitably include any error
      that they may make in the course of giving care. The conclusion that can be drawn
      is that nurses might be quite receptive to making constructive changes in their
      practice following an error, provided this situation is managed properly.

PMID- 9515647
TI  - Job satisfaction and autonomy of Hong Kong registered nurses.
AB  - This research examines job satisfaction and need for autonomy of 190 registered
      nurses in Hong Kong using a cross-sectional survey design. The level of job
      satisfaction towards six job components (autonomy, professional status, pay,
      interaction, task requirements and organizational policies) was measured using
      the Index of Work Satisfaction. Results showed that the sample was dissatisfied
      more than satisfied, they valued the job components of autonomy, professional
      status and pay more than interaction, task requirements and organizational
      policies. In addition, comparisons were made between nurses working in different
      hospitals and also different nursing units within a hospital. The level of need
      for autonomy was assessed using the autonomy subscale of the Edwards Personal
      Preference Schedule. Results showed that the level of need for autonomy of this
      group of nurses was below the mid-score of the sub-scale and there was no
      significant relationship between their satisfaction with job autonomy and their
      individual need for autonomy.

PMID- 9515649
TI  - Nursing education in Sweden: development from vocational training to higher level
      education.
AB  - Recent decades have seen several changes within Swedish nursing education. The
      length of Swedish nursing education was previously 2 years; today, however, it
      has been adapted to the rules laid down by the European Union, which means that
      it covers 3 years. Swedish nursing education was raised to university college
      level as early as 1977; however, it is only in recent years that the education
      can be said to meet the requirements placed on it. The requirement that the
      education should be scientifically based entails that the teaching staff should
      include teachers not only with nursing experience but also with a doctor's degree
      in nursing. The county councils are the authorities responsible for nursing
      education with the exception of three university colleges of nursing education
      which are independent. During the past year, however, seven nursing programmes
      have gone over to State control, and several more are discussing co-operation. A
      central evaluation made of Swedish university colleges of nursing education shows
      that 10 colleges provided education which could not be considered to correspond
      to the required level of higher education. No university college of nursing
      education has yet been accorded the right to provide education for the bachelor's
      degree. The future of the Swedish nurse is uncertain due to a large extent to the
      reorganization that has taken place within the health services.

PMID- 9515648
TI  - Job satisfaction in preceptorship and its effect on the clinical performance of
      the preceptee.
AB  - This study was designed to examine the relationship between preceptor/preceptee
      job satisfaction and preceptee clinical performance. A correlational descriptive
      design using quantitative data was employed through a mailed survey. Seventy-nine
      questionnaires were mailed to preceptors, 100 to preceptees. The response rate
      for preceptors was 49.4% while the response rate for preceptees was 33%.
      Herzberg's theory served as the conceptual framework. Three baccalaureate schools
      of nursing in Atlantic Canada comprised the setting. Analysis of data included
      frequencies, percentages, t-tests, and Pearson's product-moment correlation
      coefficient. Findings indicate that preceptors and preceptees differ
      significantly regarding aspects of their job, and their job in general. They also
      differ significantly in their rating of how often preceptees perform the
      planning/evaluation components of their care. A positive significant relationship
      exists between preceptee job satisfaction and clinical performance. No
      relationship was found to exist between preceptor job satisfaction and preceptee
      clinical performance. Additionally, in view of the limitations of the study
      (small sample, low response) limited conclusions can be drawn from the study.

PMID- 9515650
TI  - Evaluating the efficacy of reflective practice within the context of clinical
      supervision.
AB  - This paper explores the efficacy of reflective practice within the context of
      clinical supervision. It examines some potential limitations that reflective
      practice has within the context of clinical supervision drawing upon the
      literature and the early stages of the author's empirical work. It concludes that
      whilst there is considerable congruence in the use of reflective practice within
      clinical supervision sessions, there are potential disadvantages in making the
      assumption that reflective practice should be an integral part of all forms of
      clinical supervision.

PMID- 9515651
TI  - The theory and practice of health education applied to nursing: a bi-polar
      approach.
AB  - The authors contend that health education is an intrinsic part of nursing
      practice. The paper outlines two models of health education each with different
      aims, methods and outcomes and these are related explicitly to nursing practice.
      The tensions between the two approaches are discussed and whilst the authors
      acknowledge that both models constitute legitimate health education activity
      within nursing, it is argued that emphasis should be given, where practically
      possible, to the patient empowerment model. In addition the authors argue that
      the social determinants of health and health-related behaviour need to be
      considered by nurses as a powerful factor in the formation of health lifestyles.
      Therefore a range of approaches should form part of a repertoire of nursing
      health promotion interventions.

PMID- 9515652
TI  - Changes in nursing students' perceptions of nursing as they progress through
      their education.
AB  - Nursing education has shifted from the biomedical approach towards using a human
      scientific model. At the same time, the traditional role of nurses has changed
      towards professionalism owing to the development of nursing science. The purpose
      of this longitudinal study was to examine Finnish nursing students' perceptions
      of nursing after 6, 18 and 30 months of education and at the end of the education
      programme. The sample consisted of 158 students selected by means of stratified
      sampling from six specialities in nursing. Data were collected with a
      questionnaire from 26 institutes. The summarized variables were based on factor
      analysis and analysed by one-way analysis of variance. The students had
      assimilated nursing as activity which promotes human health and well-being and is
      based on professionalism. The medical-technical model was not predominant at any
      phase of the education. The students of six specialities differed only slightly
      from each other. The students' development was congruent with the aims outlined
      in the curriculum.

PMID- 9515653
TI  - Can health care assistants replace student nurses?
AB  - With the implementation of Project 2000 in the UK the traditional student nurse
      workforce has largely been replaced by health care assistants (HCAs). This study
      was carried out in Hong Kong at a time when university-based nurse education is
      gradually being introduced. Evaluation of a HCA pilot programme in an acute care
      hospital in Hong Kong provided the opportunity to examine the work of HCAs and
      hospital-based student nurses during the gradual introduction of university-based
      nurse education. The data used in this paper were drawn from a larger study
      evaluating the use of HCAs. The observational data collected at two phases after
      the introduction of HCAs were analysed using Kruskal-Wallis one way analysis of
      variance. No significant differences were found in the total amount of all types
      of activity performed by SNs and HCAs. However in the direct care type of work
      HCAs performed significantly more basic care and less technical activity than any
      level of student at phase 1 (P < 0.001) and phase 2 (P < 0.001). These
      differences in the work undertaken suggest that qualified staff do not perceive
      SNs and HCAs as equally unqualified. Thus the replacement of SNs with HCAs alone
      is likely to lead to a notable change in the role of qualified staff in terms of
      their direct and indirect care activities and in the amount of time spent
      delegating and supervising unqualified staff.

PMID- 9515654
TI  - Selection and retention of nurses.
AB  - The selection and retention of suitable nurses has occupied the thoughts of many
      people who have a vested interest in maintaining standards and avoiding loss of
      resources. By drawing conclusions from inadequate findings inappropriate
      recommendations may be made. In a study that considers the psychological profiles
      of nurses, it would appear that it is self-esteem and a 'need to be needed' that
      is a crucial facet of nurses ability to cope with the job of nursing; a job that
      encourages the characteristics of individualism, in a working environment
      involving caring, that epitomises the values of connectedness. This paradox leads
      to nurses' inability to cope and subsequently leave the profession using one of
      the many acceptable labels that are widely documented. Acceptance of the
      underlying causes for this attrition would necessitate better support services
      for vulnerable nurses allowing them to recognize their own needs, and gain a
      personal understanding of how their vulnerability might echo that of people in
      their care.

PMID- 9515655
TI  - Critical thinking ability and clinical decision-making skills among senior
      nursing students in associate and baccalaureate programmes in Korea.
AB  - This study compared Korean senior nursing students enrolled in associate degree
      programs (n = 119) and baccalaureate programs (n = 115) on measures of critical
      thinking ability and clinical decision-making skills. Samples were drawn from
      three associate degree programmes and four baccalaureate programmes accredited by
      the Korean Ministry of Education. 'Critical thinking ability' was determined by
      the Watson-Glaser Critical Thinking Appraisal and 'clinical decision-making' in
      nursing was measured by the Nursing Performance Stimulation Instrument.
      Independent sample t-tests comparing the associate degree group (mean score
      41.98) and baccalaureate group (mean score 47.22) on the critical thinking
      measure yielded significant mean differences favouring the baccalaureate group.
      The baccalaureate group (mean score 26.53) also scored significantly higher than
      the associate degree group (mean score 23.49) on clinical decision-making. Within
      the total sample (n = 234) the relationship between critical thinking and
      clinical decision-making was weak but significant (r = 0.19, P = < 0.003).

PMID- 9515656
TI  - Ethnic differences in breast self-examination practice and health beliefs.
AB  - Thirty-two African American nurses (AAN) and 78 Caucasian nurses (CN) were
      compared on breast self-examination (BSE) practice and health beliefs.
      Relationships between these variables were also examined. The Health Belief Model
      provided the framework for the study. The sample is a subset of 269 women from a
      larger study. AANs were recruited from a professional nurses' group. CNs were
      recruited from a list of female employees of a university medical centre. The
      results of t-tests revealed no significant group differences on BSE frequency (P
      = 0.06) or BSE proficiency (P = 0.10). Noted was that 42% of AANs compared to 20%
      of CNs examined their breasts 12 or more times during the year. AANs were more
      likely to consider BSE beneficial (P = 0.002) and to feel confident (P = 0.006)
      about doing BSE; CNs perceived more barriers (P = 0.001) to BSE. For AANs, BSE
      frequency and proficiency were positively related to confidence and inversely
      related to barriers; BSE frequency was also related to health motivation. For
      CNs, BSE frequency and proficiency were inversely related to seriousness.
      Implications include additional research to validate findings and to increase the
      knowledge base of all nurses regarding BSE.

PMID- 9515657
TI  - 'We have to put up with it--don't we?' The experience of being the registered
      nurse on duty, managing a violent incident involving an elderly patient: a
      phenomenological study.
AB  - The incidence of violence directed towards nurses is well known. However, despite
      guidelines and training aimed at preventing or minimizing these incidents, recent
      reports indicate an increase in their occurrence. This phenomenological study
      investigated the experiences of five registered nurses who had to manage a
      violent incident involving an elderly patient. The purpose of this was to
      discover what these nurses 'know' about the structure of such an experience and,
      through the use of Colaizzi's method of data analysis, present this knowledge in
      the form of an exhaustive description of the experience. Taped interviews were
      used to collect the data. The analytical process revealed that the experience is
      structured around five themes: professional competence, nursing identity,
      powerlessness and oppression, loss (neglected and deserted) and strategies for
      survival. The discussion analyses these themes and the relationships between
      them, highlighting the issues of nurse autonomy and exercising accountability.
      The implications for nursing practice, education and research include recognition
      of nurses as a professional group to enable autonomous practice, the ways in
      which nurses' perceptions of nursing knowledge may affect their educative role
      and the need to extend this study further to provide answers to the questions
      raised therein.

PMID- 9515658
TI  - Critical thinking: an essential element.

PMID- 9515659
TI  - Skin prick testing in general practice.

PMID- 9515660
TI  - HIV and AIDS awareness in midwives.

PMID- 9515661
TI  - Central nervous system tuberculosis--the paradox of the host immune response.

PMID- 9515662
TI  - Bacteriophages show promise as antimicrobial agents.
AB  - The emergence of antibiotic-resistant bacteria has prompted interest in
      alternatives to conventional drugs. One possible option is to use bacteriophages
      (phage) as antimicrobial agents. We have conducted a literature review of all
      Medline citations from 1966-1996 that dealt with the therapeutic use of phage.
      There were 27 papers from Poland, the Soviet Union, Britain and the U.S.A. The
      Polish and Soviets administered phage orally, topically or systemically to treat
      a wide variety of antibiotic-resistant pathogens in both adults and children.
      Infections included suppurative wound infections, gastroenteritis, sepsis,
      osteomyelitis, dermatitis, empyemas and pneumonia; pathogens included
      Staphylococcus, Streptococcus, Klebsiella, Escherichia, Proteus, Pseudomonas,
      Shigella and Salmonella spp. Overall, the Polish and Soviets reported success
      rates of 80-95% for phage therapy, with rare, reversible gastrointestinal or
      allergic side effects. However, efficacy of phage was determined almost
      exclusively by qualitative clinical assessment of patients, and details of
      dosages and clinical criteria were very sketchy. There were also six British
      reports describing controlled trials of phage in animal models (mice, guinea pigs
      and livestock), measuring survival rates and other objective criteria. All of the
      British studies raised phage against specific pathogens then used to create
      experimental infections. Demonstrable efficacy against Escherichia,
      Acinetobacter, Pseudomonas and Staphylococcus spp. was noted in these model
      systems. Two U.S. papers dealt with improving the bioavailability of phage. Phage
      is sequestered in the spleen and removed from circulation. This can be overcome
      by serial passage of phage through mice to isolate mutants that resist
      sequestration. In conclusion, bacteriophages may show promise for treating
      antibiotic resistant pathogens. To facilitate further progress, directions for
      future research are discussed and a directory of authors from the reviewed papers
      is provided.

PMID- 9515664
TI  - The bacteriological screening of donated human milk: laboratory experience of
      British Paediatric Association's published guidelines.
AB  - This study was undertaken to assess the application of the British Paediatric
      Association's (BPA) published guidelines to the bacteriological screening of
      breast milk donated to a District General Hospital milk bank. Samples of donated
      milk were subjected to bacterial counts and provisional identification after both
      24 and 48 h incubation on cysteine lactose electrolyte-deficient (CLED) and
      Columbia blood agar. 21.8% (76 out of 348) donations of milk failed to reach the
      BPA acceptable criteria. The organisms responsible for the rejection of these
      samples were all evident within 24 h incubation, and were not significantly
      confined to one medium. A large percentage of rejected samples originated from a
      small number of donor mothers; 63.2% came from one donor. In applying BPA
      guidelines, both CLED and Columbia blood agar were found to be equally effective
      in screening for unacceptable organisms in prepasteurization donated breast milk.
      The 24 h period allowed for bacteriological screening, prior to pasteurization of
      milk samples, was sufficient to allow the growth of all potentially pathogenic
      bacteria in this study. To prevent the donation of consistently contaminated
      milk, more active communication between the milk bank staff and the donor is
      recommended.

PMID- 9515663
TI  - An economic evaluation of vaccination against hepatitis A for frequent
      travellers.
AB  - This paper compares the cost of using inactive Hepatitis A vaccine relative to
      immunoglobulin as a means of protecting frequent travellers against Hepatitis A.
      The number of trips to 'at risk' areas is modelled as a Poisson process and
      results are reported in terms of the discounted gross cost per protected trip
      over a 10-year period. We find that the expected cost of immunization is lower
      with immunoglobulin for travellers visiting 'at risk' areas less than five times
      in 10 years, and lower with Hepatitis A vaccine for those visiting 'at risk'
      areas more than five times in 10 years.

PMID- 9515665
TI  - Ganciclovir and foscarnet efficacy in AIDS-related CMV polyradiculopathy.
AB  - Cytomegalovirus (CMV) polyradiculopathy is a rare complication of AIDS in which
      ascending motor weakness, sensory loss and urinary retention are associated with
      polymorphonuclear pleocytosis and positive CMV polymerase chain reaction in the
      cerebrospinal fluid (CSF). We describe three patients with this syndrome. One
      patient's paresis improved after ganciclovir therapy. Another patient
      deteriorated despite foscarnet treatment, but improved after ganciclovir was
      added. The third patient died from ascending paralysis despite ganciclovir
      foscarnet combination. Reviewing the literature, we conclude that antiviral
      treatment reduced mortality from 100 to 22%. In patients with ascending paralysis
      treatment, failure may be caused by viral drug resistance, at least in some
      patients. Risk factors for treatment failure are preceding monotherapy for other
      CMV diseases or persistent CSF pleocytosis on serial CSF analysis. We suggest
      that these patients should therefore be treated with the alternative drug or a
      ganciclovir-foscarnet combination therapy.

PMID- 9515667
TI  - Acanthamoeba castellanii: growth, encystment, excystment and biocide
      susceptibility.
AB  - Stages in the encystment and excystment processes of Acanthamoeba castellanii
      have been studied. The kinetics of encystment involved measurements of the three
      phases (pre-encystment, cyst initiation and cyst wall synthesis). Excystment,
      starting from a mature cyst, involved pre-emergence, penetration outwards of the
      cyst wall and free trophozoite. The sensitivity to biocides of trophozoites in
      the exponential growth phase, pre-encystment trophozoites, mature cysts and pre
      excystment cysts has been investigated. Some differences in relative sensitivity
      to a bisbiguanide (chlorhexidine) and a polymeric biguanide (polyhexamethylene
      biguanide) were observed, but mature cysts were always the most resistant
      cellular form.

PMID- 9515666
TI  - Prospective randomized study to compare imipenem 1.5 grams per day vs. 3.0 grams
      per day in infections of granulocytopenic patients.
AB  - The objective of this presented prospective randomized study was to compare the
      efficacy of empirical antimicrobial monotherapy with imipenem 3 x 0.5 g per day
      to 3 x 1.0 g per day for treatment of infections in neutropenic patients. A total
      of 192/220 febrile episodes were evaluable for clinical efficacy. The overall
      response rate was 53/93 (57%) vs. 57/99 (58%). Of the different infection types,
      fever of unknown origin (FUO) showed the best response, with defervescence in
      29/41 (71%) and 36/42 (86%) cases, respectively (not significant). Unfavourable
      results were found in pneumonias [5/20 (25%) vs. 4/23 (17%)]. The median time
      until persistent defervescence was equal in both groups (2 days), likewise the
      median duration of imipenem therapy in responders (7 days). The most frequent
      micro-organisms were Gram-negative, documented in 22% of the febrile episodes in
      the lower dosage group vs. 17% of all episodes in the patients with imipenem 3.0
      g per day (Gram-positives 17% vs. 14%, fungal 5% vs. 8%). In the lower dosage
      group, fever with abdominal symptoms occurred less frequently (8% vs. 15%), and
      significantly more patients tolerated imipenem without any side-effects (95.8%
      vs. 79.4%), especially regarding severe nausea/vomiting (2.1% vs. 11.8%). Of the
      initial non-responders, 35/40 (88%) vs. 41/42 (98%) were cured after therapy
      modification. There was no significant difference in the use of further
      antibiotics such as aminoglycosides, glycopeptides, ceftazidime or amphotericin
      B, except a marginally higher use of metronidazole in patients with imipenem 3.0
      g per day (3% vs. 10%). Overall, we found no significant differences in efficacy
      between the two study groups, but more frequent side-effects with imipenem 3.0 g
      per day.

PMID- 9515668
TI  - Association of Neisseria cinerea with ocular infections in paediatric patients.
AB  - Twenty-two strains of Neisseria cinerea were recovered from paediatric patients
      over a 7-year period and forwarded to the Microbial Diseases Laboratory for
      biochemical identification and/or confirmation. Eighteen of these 22 strains
      (82%) were recovered from the eyes of very young children (< or = 1 year), > 50%
      occurring during the neonatal period. The majority of eye isolates were involved
      in a variety of ocular infections including orbital cellulitis, conjunctivitis,
      and eye discharge (most common); in four of the 13 instances (31%) where
      laboratory data was available, Neisseria cinerea was recovered in pure culture.
      Neisseria cinerea isolates were often submitted to the Microbial Diseases
      Laboratory as possible 'N. gonorrhoeae' or 'Neisseria species' due to problems
      resulting from the use of commercial assays or unfamiliarity with the organism.
      These observations indicate that N. cinerea can produce eye infections in very
      young children, who presumably acquire this organism vertically from the mother
      during birth. Accurate identification of N. cinerea in such infants can preclude
      the social trauma and possible legal ramifications which can initially result
      from its misidentification as N. gonorrhoeae.

PMID- 9515669
TI  - Prevalence of antibodies against varicella zoster, herpes simplex (types 1 and
      2), hepatitis B and hepatitis A viruses among Spanish adolescents.
AB  - The aim of this cross-sectional study was to assess the seroprevalence of
      antibodies against varicella zoster (VZV), herpes simplex type 1 (HSV-1) and type
      2 (HSV-2), hepatitis B (HBV) and hepatitis A (HAV) viruses in adolescents (14-17
      years of age) in Madrid, Spain. At the study visit, demographic data and blood
      samples were obtained. The enzyme linked immunosorbent assay (ELISA) method was
      used to assess the presence of anti-VZV, anti-HSV-1, anti-HSV-2, anti-HBc and
      anti-HAV antibodies. A total of 1191 serum samples were collected. Mean age (SD)
      and male/female ratio of the study population were 15.3 (1.1) years and 0.9,
      respectively. Seroprevalences obtained were as follows: anti-VZV (94%), anti-HSV
      1 (46%), anti-HSV-2 (5%), anti-HBc (3%) and anti-HAV (5%). These data show that
      Spanish adolescents should be considered a target group for prevention programmes
      against HSV-2, HBV and HAV infections.

PMID- 9515670
TI  - Variation in morphotype, karyotype and DNA type of fluconazole resistant Candida
      albicans from an AIDS patient.
AB  - Azole-resistant oropharyngeal and oesophageal candidiasis is a recent phenomenon
      observed in patients with AIDS usually previously treated with fluconazole. Some
      variation has been observed in antifungal susceptibility testing among separate
      colonies of Candida albicans from the same patient. This raises the question of
      whether there are multiple clones present or simply phenotypic variation in
      expression of azole resistance. To address this question we took 18 isolates
      grown from multiple swabs taken before and after experimental azole therapy from
      a single HIV-positive individual with fluconazole-resistant oral candidiasis and
      compared morphotype, karyotype, PCR-based DNA typing and azole susceptibility.
      Ten of the isolates were from a single 2-day period. Amongst these 10 there were
      seven morphotypes, five karyotypes and four polymerase chain reaction (PCR)
      types. Three further morphotypes, one karyotype and two PCR types were found
      amongst the eight isolates obtained during the subsequent 4 months. Limited
      variation in susceptibility to two azoles--fluconazole and D0870--was also seen.
      This work emphasizes both the large genotype and phenotypic variability of C.
      albicans isolates in the mouth of AIDS patients with fluconazole resistance, and
      the difficulties in interpretation of present typing methods.

PMID- 9515671
TI  - Correlation of leucocyte count and erythrocyte sedimentation rate with the day of
      illness in presumed bacterial pneumonia of childhood.
AB  - We investigated the effect of the duration of illness on the white blood cell
      (WBC) and total neutrophil counts and the erythrocyte sedimentation rate (ESR) in
      untreated children with clinical and roentgenographic findings compatible with
      bacterial pneumonia. According to the duration of illness before admission, the
      patients were divided into: Group I, 48 patients ill for < 24 h; Group II, 39
      patients ill for 24-48 h; Group III, 21 patients ill for 48-72 h; and Group IV,
      eight patients ill for 72-96 h. In children with presumably bacterial pneumonia
      the number of the WBC was greater during the first 2 days of illness. Thereafter,
      the leucocyte count declined, reaching the lowest levels on the fourth day. A
      similar course was followed by the absolute number of total neutrophils. During
      the second day of illness, 92% and 72% of the patients had leucocyte counts >
      10,000 and > 15,000/mm3, respectively, whereas on the fourth day of illness only
      half of the patients had > 10,000 and one-quarter > 15,000 WBC/mm3. The ESR
      followed an opposite course to that of the WBC. During the first day of illness
      it was normal or mildly elevated, increasing steadily thereafter. The validity of
      the WBC and total neutrophil counts in conjunction with the ESR in the evaluation
      of bacterial pneumonia is augmented when the day of illness is taken into
      consideration.

PMID- 9515672
TI  - Methicillin-resistant Staphylococcus aureus: a questionnaire and microbiological
      survey of nursing and residential homes in Barking, Havering and Brentwood.
AB  - The study determined the policies and procedures for the control and prevention
      of methicillin-resistant Staphylococcus aureus (MRSA) and its prevalence among
      nursing and residential homes, and evaluated whether certain home characteristics
      such as bed size, staffing level, and type of home are related to the prevalence
      of MRSA. A 21-questionnaire survey, with primarily categorical responses, was
      mailed to the home managers of all the 121 nursing and residential homes in the
      district, following which a simple, stratified random sample of 28 (23.14%) homes
      was taken and all agreeing residents screened from multiple sites for MRSA.
      Seventy-seven (63.6%) homes returned a completed questionnaire, 13 (46.4%) of
      whom agreed to participate in the microbiological study. The response rates for
      returning questionnaires and agreeing to participate in the microbiological study
      were similar for nursing and residential homes (65% vs. 60%; 67% vs. 40%; P =
      0.12; P = 0.62), respectively. Nursing homes had a mean bed size of 30 (95%
      Confidence Interval (CI) 17-43), not significantly different from residential
      homes of 23 (95% CI 18-27; P = 0.26). The nursing homes employed a mean of 8.6
      (95% CI 4.7-12.5) staff nurses per home; significantly higher than residential
      homes with a mean of 1.6 (95% CI 0.3-2.8; P = 0.006). No significant differences
      in mean number of home care assistants employed per home (22.8; 95% CI 12.4
      33.13; and 14.4; 95% CI 11.83-16.90; P = 0.098, for nursing and residential
      homes, respectively) were observed. None of the homes had employed infection
      control practitioners. Only four (6.8%) of the responding homes stated that MRSA
      was a problem. Nursing homes were not significantly more likely to have admission
      policies for colonized person than residential homes (10/13 vs. 40/55, P = 1.00).
      Of the fifty-five (71.4%) homes who had admission policies, 40 (72.7%) stated
      that persons colonized/infected with MRSA would not be accepted, while 12 (21.8%)
      would accept such persons in single-room isolation and/or barrier nursing.
      Greater proportions of residential homes than nursing homes would not accept
      admission of persons with documented MRSA colonization (30/35 vs. 4/10, P =
      0.007). Four (9.1%) homes (three nursing) had identified a total of five
      residents colonized/infected with MRSA in 5 years prior to the survey. Two
      hundred and forty-six residents were screened (552 sites), two (0.81%) of whom
      were found to be colonized in the nose (one resident) and in the groin (two
      residents) with MRSA, giving a 2-month weighted point prevalence rate of 0.14%
      (95% CI 0.01-0.26%). We conclude that in our district the nursing staffing levels
      and control measures vary widely within these homes, while the prevalence of
      residents who are colonized/infected with MRSA is lower than in other areas. We
      suggest that the exclusion admission policy for MRSA positive patients should be
      abandoned and targeted infection control programmes be instituted.

PMID- 9515673
TI  - Ototoxicity resulting from intracochlear perfusion of Streptococcus pneumoniae in
      the guinea pig is modified by cefotaxime or amoxycillin pretreatment.
AB  - Acute changes in the electrophysiology and ultrastructure of the organ of Corti
      were studied after microperfusion of c. 5 x 10(6) CFU of serotype 2 Streptococcus
      pneumoniae D39 or Escherichia coli K-12 directly into the scala tympani of guinea
      pigs. Hearing loss was assessed by recording the auditory nerve compound action
      potential response to a 10 kHz tone pip. Mean hearing loss 3 h after pneumococcal
      perfusion (n = 4) was 44 dB, compared to 6 dB after E. coli perfusion (n = 4)
      (P<0.001). After pneumococcal perfusion, scanning electron microscopy revealed
      damage to hair cell stereocilia and cratering of the apical surface of supporting
      cells. Intraperitoneal injection of 100 mg/kg cefotaxime (n = 4) or 100 mg/kg
      amoxycillin (n = 4) 30 min before perfusion of pneumococci significantly reduced
      mean hearing loss to 23 dB (P=0.01) or 20 dB (P=0.01), respectively, and
      diminished ultrastructural damage. The data suggest that if pneumococci invade
      the inner ear during meningitis, cochlear deafness may rapidly ensue.

PMID- 9515674
TI  - Antibodies to mycoplasma fermentans in HIV-positive heterosexual patients:
      seroprevalence and association with AIDS.
AB  - There are conflicting reports concerning the prevalence of Mycoplasma fermentans
      in HIV-positive patients and its association with AIDS. Serum antibodies to M.
      fermentans were measured by a modified immunoblotting technique in 48 HIV
      positive heterosexual patients and in 30 HIV-negative heterosexual controls.
      Antibodies to M. fermentans were detected in 19 (40%) of HIV-positive patients
      and in three (10%) of the HIV-negative controls (P = 0.01). The prevalence of
      antibodies to Mycoplasma hominis and to Ureaplasma urealyticum was similar in
      both groups. In the HIV-positive group, 16/19 (84%) M. fermentans-positive
      patients developed AIDS, compared to eight of 29 (28%) M. fermentans-negative
      patients (P = 0.0004). The HIV-positive patients with antibodies to M. fermentans
      had a lower CD4+ cell count and a higher prevalence of antibodies to the other
      mycoplasma tested (P = 0.007 and P = 0.03, respectively), as compared to the
      patients without antibodies to M. fermentans. These findings may suggest that the
      presence of antibodies to M. fermentans indicate an opportunistic infection. Of
      the 19 M. fermentans-positive patients, 11 were positive on the first
      examination, and eight became positive during the follow-up period. Seven out of
      these eight patients developed antibodies to M. fermentans before the development
      of AIDS. Therefore, the possibility exists that M. fermentans might influence the
      development of AIDS.

PMID- 9515675
TI  - Multivariate model for predicting relapse in human brucellosis.
AB  - Demographic, clinical, and laboratory data from 200 consecutive patients with
      acute brucellosis were analysed with univariate and multivariate methods to
      identify correlates of relapse. A risk score for predicting relapse was then
      calculated by using Cox proportional hazard model. The independent predictors of
      relapse were temperature of 38.3 degrees C or higher, positive blood cultures at
      baseline, and the duration of symptoms before treatment <10 days. Stratification
      according to the risk score demonstrated that rates of relapse were significantly
      different between risk groups (P<0.0001). The low-risk group had a 4.5%
      probability (6 of 135) of relapse at 12 months. In contrast, relapse was present
      in 15 of 47 patients in the medium-risk group (P<0.0017); and in 12 of 18
      patients in the high-risk group (P<0.0001). This study provides a rational basis
      for estimating the risk of relapse in patients with acute brucellosis, and may be
      helpful in deciding what subjects might benefit from extra attention.

PMID- 9515677
TI  - Detection of adenovirus outbreak at a municipal swimming pool by nested PCR
      amplification.
AB  - In July 1995 an outbreak of pharyngoconjuctivitis caused by adenoviruses occurred
      among athletes participating in a swimming contest in a town in southern Greece
      (Peloponnese). At least 80 persons displayed symptoms of the illness, with the
      predominant ones being high fever, sore throat, conjuctivitis, headache, and
      abdominal pain. Poor chlorination was probably the cause of the outbreak
      (residual chlorine <0.2 mg/l), as after hyperchlorination the spread of
      adenoviruses stopped. Rapid detection of adenoviruses in the municipal swimming
      pool water by nested polymerase chain reaction (PCR) amplification allowed quick
      control of the outbreak.

PMID- 9515676
TI  - Escherichia coli bacteraemia in patients with and without haematological
      malignancies: a study of strain characters and recurrent episodes.
AB  - We compared serotypes, virulence factors and susceptibility to antibiotics of
      Escherichia coli strains isolated from 282 patients with bacteraemia. Thirty-five
      of these were neutropenic patients with haematological malignancy and 247 were
      patients with a normal or raised total white blood cell count and no
      haematological malignancy. Strains isolated from recurrent bacteraemia were also
      bio- and ribotyped. Overall, no significant difference was found between O
      serogroups, K antigens, serum sensitivity, production of haemolysin, expression
      of P-fimbriae and patterns of antibiotic susceptibility in the two groups of
      strains. The haematological patients more often than the non-haematological
      patients had an unknown focus of infection, recurrent bacteraemia, shorter
      intervals between recurrences and recurrences caused by identical strains.
      Despite a well-defined focus, six of eight non-haematological patients had
      recurrences with a strain different from the strain isolated in a previous
      episode. A possible connection between shorter intervals and recurrence with
      identical strains is discussed. We suggest that strains from recurrent E. coli
      bacteraemia are sent to a reference laboratory for serotyping and possibly
      ribotyping.

PMID- 9515678
TI  - Nested primers improve sensitivity in the detection of Helicobacter pylori by the
      polymerase chain reaction.
AB  - To investigate potential routes of spread of infection by the polymerase chain
      reaction (PCR) it is important that the technique is effective in the types of
      specimen to be investigated. To establish the limits of detection of Helicobacter
      pylori by PCR in clinical material from the gastric mucosa, faeces, dental plaque
      and oral rinses, samples were seeded with known numbers of bacteria. DNA
      extraction was followed by amplification with primers from the urease C gene.
      Nested primers were used to amplify the PCR product which was detected using a
      digoxigenin-labelled probe. Faeces or plaque inhibited the single reaction 10(2)
      10(6) fold. A second amplification using nested primers and probing increased the
      sensitivity to a level similar to that obtained with pure culture. This method is
      potentially useful with less likelihood of false negative results when trying to
      detect H. pylori by PCR in highly contaminated, clinical material.

PMID- 9515679
TI  - Prostatitis and hepatitis due to Brucella melitensis: a case report.
AB  - A case is reported of a 43-year-old man who presented prostatitis and hepatitis
      due to Brucella melitensis. His symptoms were icterus, weakness, anorexia, fever,
      and urinary discomfort. Physical examination revealed icterus and
      hepatosplenomegaly. Lymphomonocytosis, elevated erythrocyte sedimentation rate
      and abnormal liver functions had been detected in laboratory tests. Brucella
      melitensis was isolated from prostatic fluid and blood cultures.

PMID- 9515680
TI  - Successful treatment of disseminated coccidioidomycosis with amphotericin B lipid
      complex.
AB  - Coccidioidomycosis is endemic in regions of the Americas, but this infection may
      be encountered in travellers who return from an endemic region. A case is
      reported of a disseminated infection in a Hong Kong Chinese man, who was
      successfully treated with amphotericin B lipid complex (ABLC) after intolerance
      and toxicity precluded the use of other antifungal agents. Lipid-based
      formulations of amphotericin B merit further evaluation in the treatment of
      coccidioidomycosis and other systemic mycoses.

PMID- 9515681
TI  - Group A streptococcal meningitis: report of two cases.
AB  - Group A streptococcus (GAS) is a very uncommon cause of bacterial meningitis,
      with less than 30 cases reported in the last quarter of a century. A recent
      worldwide increase in the incidence and severity of disease due to Streptococcus
      pyogenes has been observed. Although a rise of incidence of cases of GAS
      meningitis has not been shown, severe and fulminant cases have been reported in
      the literature in the last few years. We performed a retrospective analysis of
      the computer data of cerebrospinal fluid cultures from July 1987 to December 1995
      at the Hadassah University Medical Center in Jerusalem, and report two cases of
      GAS meninigitis: one with a primary infection acquired through bacteraemia, in a
      2-month-old child, and another with meninigitis secondary to cranial surgery in a
      75-year-old patient. The cases are discussed and a literature review is
      presented.

PMID- 9515683
TI  - Disseminated neonatal Trichosporon beigelii infection: successful treatment with
      liposomal amphotericin B.
AB  - Trichosporon beigelii, normally a low grade pathogen, can cause disseminated
      infection in neonates with a high associated mortality. We report a case in a 25
      week gestation, 950 g female infant who had evidence of disseminated infection
      yet survived after treatment with the Liposomal form of Amphotericin B without
      any evidence of drug-induced adverse effects. A review of previous reported cases
      shows this form of disseminated mycosis to be rare and almost always fatal.

PMID- 9515682
TI  - A child case of haemophagocytic syndrome associated with cryptococcal
      meningoencephalitis.
AB  - A previously healthy 12-year-old Japanese girl developed meningoencephalitis due
      to Cryptococcus neoformans. During the course of her illness she suffered
      persistent high fever, severe pancytopenia, hypercytokinemia and liver
      dysfunction. Laboratory findings, including results of a bone marrow examination,
      strongly indicated complication by haemophagocytic syndrome (HPS). The preceding
      cryptococcal infection was thought to be a cause of the HPS because no other
      viral or bacterial infection could be confirmed. The girl died of acute
      respiratory failure during the progressive course of HPS. This may be the first
      reported case of HPS due to cryptococcal infection in an otherwise healthy child.

PMID- 9515684
TI  - Phaeohyphomycotic ulcer caused by Phialophora verrucosa: successful treatment
      with itraconazole.
AB  - We report the first well documented case of subcutaneous phaeohyphomycotic
      infection caused by Phialophora verrucosa in India. Examination of the biopsied
      tissue from an ulcerating lesion on the shin of the left leg of a 45-year-old
      woman from Bombay, India, showed numerous dematiaceous, septate, branching hyphal
      elements and thick-walled cells characteristic of phaeohyphomycosis. Cultures of
      the scrapings from the lesion and of the biopsied tissue yielded a pigmented
      fungus that was identified as P. verrucosa. Initial treatment with fluconazole
      followed by oral itraconazole for 30 days and local application of a copper
      sulphate solution resulted in complete resolution of the lesion. Treatment with
      itraconazole was continued for an additional 3 months after complete healing. No
      new lesions developed and the patient did not show jaundice, hepatosplenomegaly
      or any other signs of toxicity.

PMID- 9515685
TI  - Aspergillus flavus endocarditis in a child with neuroblastoma.
AB  - We report a case of Aspergillus flavus endocarditis in a 6-year-old boy with
      stage IV neuroblastoma with no pre-existing cardiac disease. The infection was
      successfully treated with high-dose liposomal amphotericin (AmBisome) once daily.
      Recurrence was prevented with itraconazole oral solution once daily as
      maintenance therapy. Adjunctive surgery was not required. The patient's cardiac
      function was uncompromised, but subsequent death from progressive neuroblastoma
      prevented long-term follow-up.

PMID- 9515686
TI  - Disseminated granuloma inguinale secondary to cervical infection.

PMID- 9515687
TI  - Brain abscess caused by infection with Moraxella catarrhalis following a
      penetrating injury.

PMID- 9515688
TI  - New cholera phages for Vibrio cholerae serovar O139.

PMID- 9515689
TI  - Melioidosis: problems in treatment.

PMID- 9515690
TI  - Two cases of vancomycin-resistant enterococci from Singapore.

PMID- 9515691
TI  - Capnocytophaga canimorsus in the oral flora of dogs and cats.

PMID- 9515692
TI  - Disseminated Rhodococcus equi and Nocardia farcinica infection in a patient with
      sarcoidosis.

PMID- 9515693
TI  - A search for Chlamydia psittaci in products of conception.

PMID- 9515694
TI  - Endonuclease II of coliphage T4: a recombinase disguised as a restriction
      endonuclease?
AB  - EndoII shares with restriction endonucleases the property of cleaving foreign DNA
      while leaving the endonuclease-encoding genome intact, ensuring the survival of
      one DNA species in the cell. In addition, in vivo EndoII cleaves a specific DNA
      sequence and cleavage is context dependent. These context effects extend over at
      least 1000 bp, largely limiting cleavage to once within this distance. Like
      homing endonucleases, in vivo EndoII recognizes a long, asymmetric and degenerate
      consensus sequence which has two distinct parts. Recognition of one part of the
      consensus sequence involves base-specific bonds, and recognition of the other
      involves sequence-dependent helical structure. EndoII fulfills an obvious short
      term survival role in ensuring the dominance of phage DNA in an infected cell,
      but may also have a long-term evolutionary role, producing gene-size fragments of
      foreign DNA to be enrolled in the phage genetic repertoire.

PMID- 9515695
TI  - Regulation of expression of ribosomal protein L-21 genes of Entamoeba histolytica
      and E. dispar is at the post-transcriptional level.
AB  - Two genes, EhgLE3 and Ehg34, encoding the ribosomal protein L21 (rp-L21) were
      identified and characterized from Entamoeba histolytica. Their coding regions are
      highly conserved, but their flanking regions differ significantly. Analogous
      genes (EdgLE3 and Edg34) were characterized in E. dispar. The two rp-L21 copies
      are transcribed at similar levels in the two parasites. However, their relative
      binding to the polyribosomal complex during active translation is different. In
      E. histolytica, binding of EhgLE3 transcripts to the polyribosomes is
      significantly higher in comparison with that of Ehg34 transcripts, whereas in E.
      dispar the binding pattern is inverse. The importance of each of the rp-L21
      flanking regions to gene translation was investigated by constructing hybrid
      plasmids containing the CAT reporter gene flanked by rp-L21 flanking regions. The
      plasmids were stably transfected into E. histolytica and E. dispar, and CAT mRNA
      and enzymatic activity levels were determined. All plasmids promoted
      transcription of CAT. Yet, in E. histolytica, high levels of CAT activity were
      observed only when gLE3 upstream regions flanked CAT. In contrast, in E. dispar,
      high levels of CAT activity were observed when g34 upstream regions flanked CAT.
      The downstream regions showed no significant effect on CAT translation.

PMID- 9515696
TI  - Classification and genetic characterization of pattern-forming Bacilli.
AB  - One of the more natural but less commonly studied forms of colonial bacterial
      growth is pattern formation. This type of growth is characterized by bacterial
      populations behaving in an organized manner to generate readily identifiable
      geometric and predictable morphologies on solid and semi-solid surfaces. In our
      first attempt to study the molecular basis of pattern formation in Bacillus
      subtilis, we stumbled upon an enigma: some strains used to describe pattern
      formation in B. subtilis did not have the phenotypic or genotypic characteristics
      of B. subtilis. In this report, we show that these strains are actually not B.
      subtilis, but belong to a different class of Bacilli, group I. We show further
      that commonly used laboratory strains of B. subtilis can co-exist as mixed
      cultures with group I Bacilli, and that the latter go unnoticed when grown on
      frequently used laboratory substrates. However, when B. subtilis is grown under
      more stringent semiarid conditions, members of group I emerge in the form of
      complex patterns. When B. subtilis is grown under less stringent and more motile
      conditions, B. subtilis forms its own pattern, and members of group I remain
      unnoticed. These findings have led us to revise some of the mechanistic and
      evolutionary hypotheses that have been proposed to explain pattern growth in
      Bacilli.

PMID- 9515697
TI  - Consequences of the loss of O-linked glycosylation of meningococcal type IV pilin
      on piliation and pilus-mediated adhesion.
AB  - Pili, which are assembled from protein subunits called pilin, are indispensable
      for the adhesion of capsulated Neisseria meningitidis (MC) to eukaryotic cells.
      Both MC and Neisseria gonorrhoeae (GC) pilins are glycosylated, but the effect of
      this modification is unknown. In GC, a galactose alpha-1,3-N-acetyl glucosamine
      is O-linked to Ser-63, whereas in MC, an O-linked trisaccharide is present
      between residues 45 and 73 of pilin. As Ser-63 was found to be conserved in pilin
      variants from different strains, it was replaced by Ala in two MC variants to
      test the possible role of this residue in pilin glycosylation and modulation of
      pili function. The mutated alleles were stably expressed in MC, and the proteins
      they encoded migrated more quickly than the normal protein during SDS-PAGE. As
      controls, neighbouring Asn-61 and Ser-62 were replaced by an Ala with no effect
      on electrophoretic mobility. Silver staining of purified pilin obtained from MC
      after oxidation with periodic acid confirmed the loss of glycosylation in the Ser
      63-->Ala pilin variants. Mass spectrometry of HPLC-purified trypsin-digested
      peptides of pilin and Ser-63-->Ala pilin confirmed that peptide 45-73 has the
      molecular size of a glycopeptide in the wild type. In strains producing non
      glycosylated pilin variants, we observed that (i) no truncated S pilin monomer
      was produced; (ii) piliation was slightly increased; and (iii) presumably as a
      consequence, adhesiveness for epithelial cells was increased 1.6- to twofold in
      these derivatives. In addition, pilin monomers and/or individual pilus fibres,
      obtained after solubilization of a crude pili preparation in a high pH buffer,
      were reassociated into insoluble aggregates of pili more completely with non
      glycosylated variants than with the normal pilin. Taken together, these data
      eliminate a major role for pilin glycosylation in piliation and subsequent pilus
      mediated adhesion, but they demonstrate that glycosylation facilitates
      solubilization of pilin monomers and/or individual pilus fibres.

PMID- 9515698
TI  - Alginate, inorganic polyphosphate, GTP and ppGpp synthesis co-regulated in
      Pseudomonas aeruginosa: implications for stationary phase survival and synthesis
      of RNA/DNA precursors.
AB  - The regulatory protein AlgR2 in Pseudomonas aeruginosa positively regulates
      nucleoside diphosphate kinase (Ndk) and succinyl-CoA synthetase, enzymes critical
      in nucleoside triphosphate (NTP) formation. AlgR2 positively regulates the
      production of alginate, GTP, ppGpp and inorganic polyphosphate (poly P). An algR2
      mutant with low levels of these metabolites has them restored by introducing and
      overexpressing either the algR2 or the ndk gene into the algR2 mutant. Thus, Ndk
      is involved in the formation of these compounds and largely prevents the death of
      the algR2 mutant, which occurs early in the stationary phase. We demonstrate that
      the 12 kDa Ndk-pyruvate kinase (Pk) complex, previously shown to generate
      predominantly GTP instead of all the NTPs, has a low affinity for the
      deoxynucleoside diphosphates and cannot generate the dNTPs needed for DNA
      replication and cell division; this complex may thus be involved in regulating
      the levels of both NTPs and dNTPs that modulate cell division and survival in the
      stationary phase.

PMID- 9515699
TI  - Biochemical basis of hyper-recombinogenic activity of Pseudomonas aeruginosa RecA
      protein in Escherichia coli cells.
AB  - The replacement of Escherichia coli recA gene (recA[Ec]) with the Pseudomonas
      aeruginosa recA(Pa) gene in Escherichia coli cells results in constitutive hyper
      recombination (high frequency of recombination exchanges per unit length of DNA)
      in the absence of constitutive SOS response. To understand the biochemical basis
      of this unusual in vivo phenotype, we compared in vitro the recombination
      properties of RecA(Pa) protein with those of RecA(Ec) protein. Consistent with
      hyper-recombination activity, RecA(Pa) protein appeared to be more proficient
      both in joint molecule formation, producing extensive DNA networks in strand
      exchange reaction, and in competition with single-stranded DNA binding (SSB)
      protein for single-stranded DNA (ssDNA) binding sites. The RecA(Pa) protein
      showed in vitro a normal ability for cleavage of the E. coli LexA repressor (a
      basic step in SOS regulon derepression) both in the absence and in the presence
      (i.e. even under suboptimal conditions for RecA(Ec) protein) of SSB protein.
      However, unlike other hyper-recombinogenic proteins, such as RecA441 and RecA730,
      RecA(Pa) protein displaced insufficient SSB protein from ssDNA at low magnesium
      concentration to induce the SOS response constitutively. In searching for
      particular characteristics of RecA(Pa) in comparison with RecA(Ec), RecA441 and
      RecA803 proteins, RecA(Pa) showed unusually high abilities: to be resistant to
      the displacement by SSB protein from poly(dT); to stabilize a ternary complex
      RecA::ATP::ssDNA to high salt concentrations; and to be much more rapid in both
      the nucleation of double-stranded DNA (dsDNA) and the steady-state rate of dsDNA
      dependent ATP hydrolysis at pH7.5. We hypothesized that the high affinity of
      RecA(Pa) protein for ssDNA, and especially dsDNA, is the factor that directs the
      ternary complex to bind secondary DNA to initiate additional acts of
      recombination instead of to bind LexA repressor to induce constitutive SOS
      response.

PMID- 9515701
TI  - Leucine alters the interaction of the leucine-responsive regulatory protein (Lrp)
      with the fim switch to stimulate site-specific recombination in Escherichia coli.
AB  - The leucine-responsive regulatory protein (Lrp) is a global regulator that
      controls the expression of numerous operons in Escherichia coli. Lrp can act as a
      repressor or as an activator of transcription with its effects being potentiated,
      repressed or unaffected by the presence of exogenous leucine. The phase variation
      of type 1 fimbria in E. coli provides a unique system in which to investigate the
      effects of leucine on Lrp, as it is the only known example in which Lrp is a
      positive regulator and leucine potentiates this effect. Previous studies
      determined that Lrp binds with high affinity to two sites within the fim switch
      (fim sites 1 and 2), and binding to these sites stimulates recombination. Here,
      it is shown that, even though leucine stimulates the fim switch in vivo, it
      nevertheless causes a slight decrease in Lrp binding to the fim switch in vitro.
      These contradictory results are explicable by the finding that Lrp binding to a
      third region adjacent to fim sites 1 and 2 inhibits recombination. According to
      this model, leucine stimulates recombination by selectively disrupting Lrp
      binding to this newly characterized region, while having little or no effect on
      Lrp binding to fim sites 1 and 2.

PMID- 9515700
TI  - Cell cycle arrest in Era GTPase mutants: a potential growth rate-regulated
      checkpoint in Escherichia coli.
AB  - Era is a low-molecular-weight GTPase essential for Escherichia coli viability.
      The gene encoding Era is found in the rnc operon, and the synthesis of both RNase
      III and Era increases with growth rate. Mutants that are partially defective in
      Era GTPase activity or that are reduced in the synthesis of wild-type Era become
      arrested in the cell cycle at the predivisional two-cell stage. The partially
      defective Era GTPase mutation (era1) suppresses several temperature-sensitive
      lethal alleles that affect chromosome replication and chromosome partitioning but
      not cell division. Our results suggest that Era plays an important role in cell
      cycle progression at a specific point in the cycle, after chromosome partitioning
      but before cytokinesis. Possible functions for Era in cell cycle progression and
      the initiation of cell division are discussed.

PMID- 9515702
TI  - A second prepilin peptidase gene in Escherichia coli K-12.
AB  - Escherichia coli K-12 strains grown at 37 degrees C or 42 degrees C, but not at
      30 degrees C, process the precursors of the Neisseria gonorrhoeae type IV pilin
      PilE and the Klebsiella oxytoca type IV pseudopilin PulG in a manner reminiscent
      of the prepilin peptidase-dependent processing of these proteins that occurs in
      these bacteria. Processing of prePulG in Escherichia coli requires a glycine at
      position -1, as does processing by the cognate prepilin peptidase (PulO), and is
      unaffected by mutations that inactivate several non-specific proteases. These
      data suggested that E. coli K-12 has a functional prepilin peptidase, despite the
      fact that it does not itself appear to express either type IV pilin or
      pseudopilin genes under the conditions that allow prePilE and prePulG processing.
      The E. coli K-12 genome contains two genes encoding proteins with significant
      sequence similarity to prepilin peptidases: gspO at minute 74.5 and pppA (f310c)
      at minute 67 on the genetic map. We have previously obtained evidence that gspO
      encodes an active enzyme but is not transcribed. pppA was cloned and shown to
      code for a functional prepilin peptidase capable of processing typical prepilin
      peptidase substrates. Inactivation of pppA eliminated the endogenous,
      thermoinducible prepilin peptidase activity. PppA was able to replace PulO
      prepilin peptidase in a pullulanase secretion system reconstituted in E. coli
      when expressed from high-copy-number plasmids but not when present in a single
      chromosomal copy. The analysis of pppA-lacZ fusions indicated that pppA
      expression was very low and regulated by the growth temperature at the level of
      translation, in agreement with the observed temperature dependence of PppA
      activity. Polymerase chain reaction and Southern hybridization analyses revealed
      the presence of the pppA gene in 12 out of 15 E. coli isolates.

PMID- 9515703
TI  - Use of asymmetric cell division and spoIIIE mutants to probe chromosome
      orientation and organization in Bacillus subtilis.
AB  - Soon after the onset of sporulation in Bacillus subtilis, asymmetric cell
      division occurs to generate the differentiating prespore and mother cell types.
      Formation of the septum close to the cell pole initially bisects the nucleoid
      destined for the prespore, trapping only about one-third of the DNA in the small
      compartment. The remaining part of the chromosome is then transported through the
      septum. spoIIIE mutant cells fail to transfer the DNA and arrest with only
      partially segregated prespore chromosomes. Previous work has shown that the
      orientation of the chromosome at the time of septation is not random. Here, we
      use both physical and genetic methods to characterize the trapped DNA. The
      results show that the chromosome has a very specific orientation at the time of
      septation, consistent with the action of a centromere-like sequence near oriC.
      They also demonstrate that the chromosome is folded, or otherwise organized, in a
      highly ordered manner.

PMID- 9515704
TI  - Regulation of RssB-dependent proteolysis in Escherichia coli: a role for acetyl
      phosphate in a response regulator-controlled process.
AB  - Sigma(S) (RpoS) is a highly unstable global regulatory protein in Escherichia
      coli, whose degradation is inhibited by various stress signals, such as carbon
      starvation, high osmolarity and heat shock. As a consequence, these stresses
      result in the induction of sigma(S)-regulated stress-protective proteins. The two
      component-type response regulator, RssB, is essential for the rapid proteolysis
      of sigma(S) and is probably involved in the transduction of some of these stress
      signals. Acetyl phosphate can be used as a phosphodonor for the phosphorylation
      of various response regulators in vitro and, in the absence of the cognate sensor
      kinases, acetyl phosphate can also modulate the activities of several response
      regulators in vivo. Here, we demonstrate increased in vivo half-lives of sigma(S)
      and the RpoS742::LacZ hybrid protein (also a substrate for RssB-dependent
      proteolysis) in acetyl phosphate-free (pta-ackA) deletion mutants, even though no
      sensor kinase was eliminated. The in vivo data indicate that acetyl phosphate
      acts through the response regulator, RssB. In vitro, efficient phosphotransfer
      from radiolabelled acetyl phosphate to the Asp-58 residue of RssB (the expected
      site of phosphorylation in the RssB receiver domain) was observed. Via such
      phosphorylation, acetyl phosphate may thus modulate RssB activity even in an
      otherwise wild-type background. While acetyl phosphate is not essential for the
      transduction of specific environmental stress signals, it could play the role of
      a modulator of RssB-dependent proteolysis that responds to the metabolic status
      of the cells reflected in the highly variable cellular acetyl phosphate
      concentration.

PMID- 9515705
TI  - Use of signature-tagged transposon mutagenesis to identify Vibrio cholerae genes
      critical for colonization.
AB  - The pathogenesis of cholera begins with colonization of the host intestine by
      Vibrio cholerae. The toxin co-regulated pilus (TCP), a fimbrial structure
      produced by V. cholerae, is absolutely required for colonization (i.e. the
      persistence, survival and growth of V. cholerae in the upper intestinal milieu),
      but many other aspects of the colonization process are not well understood. In
      this study, we use signature-tagged transposon mutagenesis (STM) to conduct a
      screen for random insertion mutations that affect colonization in the suckling
      mouse model for cholera. Of approximately 1100 mutants screened, five mutants
      (approximately 0.5%) with transposon insertions in TCP biogenesis genes were
      isolated, validating the use of STM to identify attenuated mutants. Insertions in
      lipopolysaccharide, biotin and purine biosynthetic genes were also found to cause
      colonization defects. Similar results were observed for mutations in homologues
      of pta and ptfA, two genes involved in phosphate transfer. Finally, our screen
      identified several novel genes, disruption of which also caused colonization
      defects in the mouse model. These results demonstrate that STM is a powerful
      method for isolating colonization-defective mutants of V. cholerae.

PMID- 9515706
TI  - PepA, a secreted protein of Pseudomonas aeruginosa, is necessary for cytotoxicity
      and virulence.
AB  - Pseudomonas aeruginosa is an opportunistic pathogen and a leading cause of
      hospital-acquired pneumonia. We identified a 73kDa protein, designated
      Pseudomonas exoprotein A (PepA), that was secreted by P. aeruginosa strain PA103.
      PepA was necessary for in vitro killing of epithelial cells as well as virulence
      in a mouse model of acute pneumonia. Several properties of PepA suggested that it
      was secreted by a type III system. Secretion occurred without cleavage of a
      signal peptide and in low-calcium environments in the presence of a divalent
      cation chelator, as is the case for characterized P. aeruginosa type III secreted
      proteins. Secretion of PepA was absent from isogenic mutants with defective type
      III pathways. Finally, amino-terminal peptide sequence analysis indicated that
      the amino-terminal five residues of PepA were identical to those of ExoS and
      ExoT, two type III secreted proteins of P. aeruginosa. After secretion, PepA
      underwent cleavage at two sites, each with the sequence A-X-K-S, suggesting that
      the cleavage may be caused by a protease. The gene encoding PepA, designated
      pepA, was cloned and sequenced, and comparisons with the genetic database using
      BLAST alignments indicated that the nucleotide sequence of pepA and the inferred
      protein sequence of PepA had no homology to known sequences. A nucleotide
      sequence identical to the consensus element for binding of ExsA, a
      transcriptional activator of P. aeruginosa type III secretion genes, was located
      84 bp 5' of the translational start codon. Analysis of transposon insertion
      mutants indicated that the carboxy terminus was required for cytotoxicity.
      Examination of respiratory clinical isolates demonstrated that pepA was a
      variable trait and probably acquired by horizontal transmission. Consistent with
      this hypothesis was the identification of a putative insertion element 94 bp 5'
      of the PepA translational start site. Analysis of G + C content of the PepA
      coding sequence and the adjacent insertion element suggested that they were
      acquired together from a different species. In summary, PepA is a secreted
      protein of P. aeruginosa that is necessary for epithelial cell cytotoxicity in
      vitro and virulence in a mouse model of pneumonia.

PMID- 9515707
TI  - The bacteriophage T4 AsiA protein: a molecular switch for sigma 70-dependent
      promoters.
AB  - The AsiA protein, encoded by bacteriophage T4, inhibits Esigma70-dependent
      transcription at bacterial and early-phage promoters. We demonstrate that the
      inhibitory action of AsiA involves interference with the recognition of the -35
      consensus promoter sequence by host RNA polymerase. In vitro experiments were
      performed with a C-terminally labelled sigma factor that is competent for
      functional holoenzyme reconstitution. By protease and hydroxyl radical protein
      footprinting, we show that AsiA binds region 4.2 of sigma70, which recognizes the
      -35 sequence. Direct interference with the recognition of the promoter at this
      locus is supported by two parallel experiments. The stationary-phase sigma factor
      containing holoenzyme, which can initiate transcription at promoters devoid of a 
      35 region, is insensitive to AsiA inhibition. The recognition of a galP1 promoter
      by Esigma70 is not affected by the presence of AsiA. Therefore, we conclude that
      AsiA inhibits transcription from Escherichia coli and T4 early promoters by
      counteracting the recognition of region 4.2 of sigma70 with the -35 hexamer.

PMID- 9515708
TI  - A pathway-specific transcriptional activator regulates late steps of clavulanic
      acid biosynthesis in Streptomyces clavuligerus.
AB  - A Streptomyces clavuligerus gene (designated claR) located downstream from the
      gene encoding clavaminate synthase in the clavulanic acid biosynthetic gene
      cluster is involved in regulation of the late steps in clavulanic acid
      biosynthesis. Nucleotide sequence analysis and database searching of ClaR
      identified a significant similarity to the helix-turn-helix motif (HTH) region of
      LysR transcriptional regulators. A gene replacement mutant disrupted in claR was
      unable to produce clavulanic acid, suggesting that claR is essential for
      clavulanic acid biosynthesis. Furthermore, the accumulation of clavaminic acid in
      the claR mutant suggested that ClaR regulates the late steps in the clavulanic
      acid pathway, i.e. those involved in the conversion of clavaminic acid to
      clavulanic acid. Transcriptional analysis using RNA isolated from the wild type
      and the claR mutant showed that the expression of the putative late genes, but
      not the early genes, was regulated by ClaR. High-resolution S1 nuclease analysis
      of claR suggested that it is expressed as a monocistronic transcript and also as
      a bicistronic transcript along with the late gene orf-9. The transcription start
      site of the monocistronic claR transcript was identified as a C residue 155
      nucleotides upstream from the claR start codon.

PMID- 9515709
TI  - Membrane targeting of RecA during genetic transformation.
AB  - Recombination in prokaryotes and eukaryotes is mediated by the RecA family of
      proteins. Although the interactions between RecA and DNA are well studied, the
      cellular location of these interactions is not known. Using genetic
      transformation of Streptococcus pneumoniae as a model system, there was increased
      expression of a protein, colligrin, and RecA, products of the rec locus during
      genetic transfer. These proteins formed a complex and were found associated with
      the membranes of genetically competent cells. With immunoelectron microscopy and
      subcellular fractionation, we showed that the induction of competence led to the
      translocation of RecA and colligrin to the membrane and to the formation of
      clusters of RecA in a colligrin-dependent step. Based on the behaviour of
      colligrin and RecA during genetic exchange and the numerous proteins in
      prokaryotes and eukaryotes with domains similar to colligrin, we suggest that
      there may exist a family of proteins, which gathers macromolecules at specific
      sites in biological membranes.

PMID- 9515710
TI  - Xanthine dehydrogenase from the phototrophic purple bacterium Rhodobacter
      capsulatus is more similar to its eukaryotic counterparts than to prokaryotic
      molybdenum enzymes.
AB  - Fourteen Rhodobacter capsulatus mutants unable to grow with xanthine as sole
      nitrogen source were isolated by random Tn5 mutagenesis. Five of these Tn5
      insertions were mapped within two adjacent chromosomal EcoRI fragments
      hybridizing to oligonucleotides synthesized according to conserved amino acid
      sequences of eukaryotic xanthine dehydrogenases. DNA sequence analysis of this
      region revealed two open reading frames, designated xdhA and xdhB, encoding
      xanthine dehydrogenase. The deduced amino acid sequence of XDHA contains binding
      sites for two [2Fe-2S] clusters and FAD, whereas XDHB is predicted to contain the
      molybdopterin cofactor. In contrast to R. capsulatus, these three cofactor
      binding sites reside within a single polypeptide chain in eukaryotic xanthine
      dehydrogenases. The amino acid sequence of xanthine dehydrogenase from R.
      capsulatus showed a higher degree of similarity to eukaryotic xanthine
      dehydrogenases than to the xanthine dehydrogenase-related aldehyde oxidoreductase
      from Desulphovibrio gigas. The expression of an xdhA-lacZ fusion was induced when
      hypoxanthine or xanthine was added as sole nitrogen source. Mutations in nifR1
      (ntrC) and nifR4 (rpoN, encoding sigma54) had no influence on xdh gene
      expression. A putative activator sensing the availability of substrate seems to
      respond to xanthine but not to hypoxanthine. The transcriptional start site of
      xdhA was mapped by primer extension analysis. Comparison with known promoter
      elements revealed no significant homology. Xanthine dehydrogenase from R.
      capsulatus was purified to homogeneity. The enzyme consists of two subunits with
      molecular masses of 85 kDa and 50 kDa respectively. N-terminal amino acid
      sequencing of both subunits confirmed the predicted start codons. The molecular
      mass of the native enzyme was determined to be 275 kDa, indicating an alpha2beta2
      subunit structure. Analysis of the molybdenum cofactor of xanthine dehydrogenase
      from R. capsulatus revealed that it contains the molybdopterin cofactor and not a
      molybdopterin dinucleotide derivative.

PMID- 9515711
TI  - Evolution and horizontal transfer of an entire biosynthetic pathway for
      cytochrome c biogenesis: Helicobacter, Deinococcus, Archae and more.

PMID- 9515712
TI  - Downstream box: a hidden translational enhancer.

PMID- 9515713
TI  - Dual-color flow cytometric detection of fluorescent proteins using single-laser
      (488-nm) excitation.
AB  - The ability to analyze independently the expression of multiple reporter gene
      constructs within single cells is a potentially powerful application of flow
      cytometry. In this paper, we explore the simultaneous detection of two variants
      of the reporter molecule, green fluorescent protein (GFP) that both fluoresce
      when excited with 488-nm light. One of these, enhanced GFP (EGFP) (excitation
      max. 490 nm; > 90% efficiency at 488 nm), has been widely used for studies that
      involve flow cytometric detection of reporter gene expression. As a partner for
      EGFP, we employed a recently described variant termed enhanced yellow fluorescent
      protein (EYFP) (excitation max. 513 nm; approximately 35% efficiency at 488 nm).
      Using 488-nm excitation, EYFP fluorescence could be readily detected following
      expression of the gene in murine fibroblasts and this signal was comparable in
      intensity to that obtained from EGFP. Importantly, we describe an optical filter
      configuration that permits the fluorescence signals from both proteins to be
      distinguished by flow cytometry, despite their similar emission maxima. This
      filter configuration employed a 510/20-nm bandpass filter for EGFP detection, a
      550/30-nm bandpass filter for EYFP detection, and a 525-nm short-pass dichroic
      mirror to separate the two signals. With these filters, expression of either
      reporter protein could be detected, alone or in combination, within a mixed
      population of cells over a broad range of signal intensities.

PMID- 9515714
TI  - Fast-FISH technique for rapid, simultaneous labeling of all human centromeres.
AB  - Fluorescence in situ hybridization (FISH) has become a powerful tool in
      chromosome analysis. This report describes the systematic optimization of the
      Fast-FISH technique for centromere labeling of human metaphase chromosomes for
      radiobiological dosimetry purposes. For the present study, the hybridization
      conditions and the efficiency of two commercially available alpha-satellite DNA
      probes were compared ("human chromosome 1 specific", Oncor, Gaithersburg, MD, vs.
      "all-human chromosomes specific", Boehringer-Mannheim, Germany). These probes
      were hybridized to human lymphocyte metaphase plates by using a hybridization
      buffer without formamide and without any other equivalent denaturing chemical
      agents. The results indicate the suitability of the method for automated image
      analysis on the basis of thresholding. The optimal conditions concerning
      hybridization time and temperature were determined by a systematic quantitative
      evaluation of the fluorescent labeling sites after the hybridization procedures.
      Under defined "low stringency" conditions, we found that the "human chromosome 1
      specific" DNA probe labeled not only the centromere of the human chromosome 1 but
      also the other human centromeres in the same way as the "all-human chromosome
      specific" DNA probe. The optimized conditions to complete all centromere labeling
      were applied to the detection of dicentric chromosomes on irradiated human
      lymphocyte samples (gamma-rays of 60Co source, 0.5 Gy/min, for doses of 1, 3, and
      4 Gy). The yield of dicentrics was determined after Fast-FISH and compared with
      results obtained after Giemsa staining. These results are very compatible and
      indicate that, because of its simplicity, this optimized Fast-FISH procedure
      would be useful for fast screening purposes in biological dosimetry after
      accidental overexposure.

PMID- 9515715
TI  - Detection of chromosomal gains and losses in comparative genomic hybridization
      analysis based on standard reference intervals.
AB  - Criteria for detection of chromosome aberrations by Comparative Genomic
      Hybridization (CGH) are not standardized and improvement of this part of the
      analysis is of paramount importance to the applicability of the technique. The
      aim of this work was to suggest CGH detection criteria that increase the
      specificity and sensitivity and at the same time include chromosome regions
      previously excluded from CGH analysis. We analyzed 33 hybridizations with normal
      DNA and modified our CGH software in order to use a selection of these normal
      analyses as a model for interpretation of analyses of unknown samples. This
      approach was successfully tested on 14 samples with known aberrations.

PMID- 9515716
TI  - Comparison of fluorescein isothiocyanate- and Texas red-conjugated nucleotides
      for direct labeling in comparative genomic hybridization.
AB  - In this study, we investigated whether fluorescein isothiocyanate (FITC)-labeling
      of test DNA and Texas-red (TR) labeling of reference DNA in comparative genomic
      hybridization (CGH) experiments cause the results to differ from those obtained
      using the opposite combination (reverse labeling). Analysis was performed on a
      total of 20 DNA specimens consisting of 13 frozen bone marrow aspirates from
      patients with acute myeloid leukemia, and fresh peripheral blood samples from
      seven healthy donors. For CGH, one aliquot from each test DNA sample was labeled
      using nick-translation with FITC-dUTP and another with TR-dUTP. Afterwards, the
      FITC-dUTP and TR-dUTP-labeled test DNAs were hybridized to TR-dUTP- and FITC-dUTP
      labeled normal reference DNAs, respectively. The results using the two
      combinations were compared with each other and with the results of G-banding
      karyotype analysis. Karyotype data was used to detect artifacts known to occur in
      some chromosome regions in CGH analysis. The control DNAs labeled with FITC or TR
      showed no DNA copy number changes. Regardless of the fluorochrome employed for
      labeling, no DNA copy number changes were detected using CGH in patients with
      normal karyotypes, nor in patients whose karyotype aberrations were present in
      less than 40% of cells. In the remaining patients, CGH revealed DNA copy number
      changes that coincided with the results of the G-banding analysis. Hybridization
      artifacts known to occur in CGH experiments affecting chromosome regions 1p33
      pter, 16p, 17p, 19, and 22 were observed in 15-23% of the tumor samples labeled
      with FITC, but not in samples labeled with TR. In addition, other previously
      unreported overrepresentations affecting 7q21, 9q34, 16q, 17q, and chromosome 20
      were observed at very low frequencies in up to 10% of the samples when FITC was
      used to label test DNA. However, when TR was used, overrepresentations were
      observed at 4q13-q21, 11q21-q23, 13q21-qter, and Xq21-q22, whereas 19p was
      underrepresented. The results demonstrate that TR-labeling confirms abnormalities
      detected using FITC-labeling and reduces hybridization artifacts in the known
      problematic regions of the human genome.

PMID- 9515717
TI  - A novel flow cytometric method for the quantification of p53 gene expression.
AB  - We describe a rapid and simple flow cytometry technique for the detection and
      quantification of p53 in several human cell lines, including an adenocarcinoma
      cell line (SW 626) having a mutant (m) p53, and a pre-B leukemia cell line (NALM
      6) having wild-type (wt) p53. By introducing a second antibody coupled to RPE
      fluorescence, the discrimination between control and specific peaks was improved
      over that achieved with methods used previously. To quantify the content of p53
      molecules in the cells, we used a series of beads with the capability to bind
      mouse monoclonal IgG antibodies. p53 cell content, expressed as antibody binding
      capacity (ABC), was directly quantified from logarithmic scattergrams; the
      results were reproducible in all cell lines tested. Flow cytometric results were
      compared with those of a standard immunocytochemistry method routinely used for
      the detection of p53 in cells, and found to be in correlation. Furthermore,
      cytometric data also reflect ELISA determinations. In summary, we showed for the
      first time that (i) p53 can be clearly detected by flow cytometry in various cell
      lines, (ii) p53 can be quantitated in terms of number of molecules per cell, and
      (iii) it can be easily monitored as a function of time after stimulation.

PMID- 9515718
TI  - A novel bioassay for P-glycoprotein functionality using cytochalasin D.
AB  - The functional contribution of both P-glycoprotein (P-gp) and the multidrug
      resistance-associated protein (MRP) to multidrug resistance (MDR) in tumor cells
      is commonly determined by drug cytotoxicity and/or accumulation/efflux tests. We
      report on a bioassay developed for the specific detection of functional P-gp
      levels and the efficacy of related chemosensitizers (CD-P-gp-assay). The assay is
      based on the flow cytometric measurement of changes in the > or = G2M cell cycle
      compartment which are due to the induction of polykaryons after exposure of
      proliferating cells to three defined cytochalasin D (CD) concentrations with and
      without verapamil. As demonstrated in 13 well-characterized MDR cell models (20
      resistant sublines), there is a significant correlation between cytokinesis
      blocking CD doses, as well as responsiveness to chemosensitizers and MDR1 gene
      expression (mRNA and P-gp) allowing discrimination between different levels of P
      gp-MDR. CD-P-gp-assay specificity was assessed by testing 23 compounds: 19 known
      as potent inhibitors of P-gp-MDR, some of them, though to a lesser extent, also
      of MRP-MDR; 1 inhibiting MRP-but not P-gp-MDR; 3 inactive in both types of MDR. A
      modulation of CD activity was confined exclusively to both P-gp-expressing cell
      lines and P-gp chemosensitizers. CD cytoskeletal activity measured by FACS is a
      specific and sensitive tool with which to detect functional P-gp and related
      chemosensitizers.

PMID- 9515719
TI  - Rapid flow cytometric identification of putative CD14- and CD64- dendritic cells
      in whole blood.
AB  - Blood dendritic cells (DCs) may be identified as mononuclear leucocytes with high
      expression of HLA-DR, but lacking the antigens CD3, CD14, CD16, CD19, and CD56,
      which are characteristically expressed by T cell, monocytes, B cells, and natural
      killer cells. However, some DCs have recently been reported to express the
      monocyte-associated antigen CD14; also some monocytes may shed CD14 and so appear
      to be CD14-. It is therefore possible that the expression of CD64, which is
      absent on blood DCs but which is expressed by both CD14+ and CD14- monocytes may
      better distinguish DCs from monocytes. DCs were identified by flow cytometry as
      mononuclear leucocytes with the phenotype HLA-DR+, CD2-, CD16-, CD19-, CD57-, and
      either CD14- or CD64- and hence are described herein as either CD14- DCs or CD64-
      DCs, respectively. CD14- DCs and CD64- DCs occurred, respectively, at a
      concentration of 65 +/- 48 x 10(6) cells 1(-1) and 149 +/- 103 x 10(6) cells 1(
      1) (mean +/- S.D.) in samples of peripheral blood (corresponding, respectively,
      to 3.0 +/- 1.8% and 6.6 +/- 3.8% of the mononuclear cells). The expression of
      CD14 and CD64 on monocytes in blood was also investigated. Cells with the
      immunophenotype CD14- CD64+ comprised 12.7 +/- 3.3% of the monocyte population
      and had high expression of HLA-DR. DCs identified as CD14- or CD64- were isolated
      by flow cytometric sorting, prepared for electron microscopy, and both were found
      to have the characteristic morphology of resting DCs. We conclude that
      mononuclear cells with the phenotype HLA-DR+, CD3-, CD16-, CD19-, CD56-, and CD64
      are blood DCs that may be CD14+ or CD14-. The method described therefore
      provides a more accurate and rapid means of identifying circulating DCs.

PMID- 9515721
TI  - Analysis of image sequences in fluorescence videomicroscopy of stationary
      objects.
AB  - Fluorescence videomicroscopy allows the temporal behavior of biological specimens
      to be studied at the cellular level. We describe two types of methods that can be
      used for extracting quantitative information from image sequences: the modeling
      approach, which is mainly local, and multivariate statistical analysis, which
      provides a global approach. The potentials for use of these two methods are
      illustrated through a simulation example and actual examples dealing with the
      study of chloride secretion by airway epithelial cells. We define some guidelines
      for making a choice between these two approaches, bearing in mind that a blend of
      these two methodologies is also possible.

PMID- 9515720
TI  - Apoptosis induced with different cycle-perturbing agents produces differential
      changes in the fluorescence lifetime of DNA-bound ethidium bromide.
AB  - Fluorescence lifetime analysis was used in combination with conventional flow
      cytometric analysis to monitor changes in residual chromatin in apoptotic HL-60
      cell populations following treatment with camptothecin, cycloheximide, genistein,
      H7, and gamma radiation. Data presented show that all of these metabolic
      inhibitors, which act through different signaling cascades, produce apoptotic
      subpopulations with decreased but different lifetimes for DNA-bound ethidium
      bromide (EB). Additionally, treatment with certain agents reduced the
      fluorescence lifetime in the apoptotic cells prior to extensive endonuclease
      degradation of DNA and the appearance of the typical sub-G0/G1 peak in the DNA
      histogram. A lifetime value of 21.15 +/- 0.12 ns was obtained for EB bound to
      nonapoptotic cells, while values for EB bound to the apoptotic subpopulations
      following treatment with the different agents were: camptothecin, 19.87 +/- 0.08
      ns; cycloheximide, 19.39 +- 0.02 ns; H7, 19.77 +/- 0.03 ns; genistein, 20.04 +/-
      0.04 ns; and gamma radiation, 19.67 +/- 0.03 ns. Traditional methods of analysis,
      including gel electrophoresis or morphology assessment, revealed no significant
      differences among apoptotic subpopulations induced by treatment with these
      agents. Our data suggest that the mode of action of the various agents induces
      structural changes in chromatin organization that differentially alter
      accessibility of DNA to endonuclease digestion. Subsequent fluorescence lifetime
      analysis appears sensitive to the resulting differences in the residual chromatin
      in apoptotic cells following DNA cleavage. Results presented indicate that
      lifetime analysis, used in conjunction with conventional flow cytometry, can be
      useful for early detection of apoptosis-induced chromatin changes and may also
      potentially provide new information on the effects of different apoptosis
      inducing agents.

PMID- 9515722
TI  - A rapid method for the preparation of single-cell suspensions from solid tissues.
AB  - A simple and rapid methodology for the preparation of single-cell suspension from
      animal tissues is described. It uses a device called a "tissue press" to mince
      the tissue into small pieces of desired sizes which are then dissociated into
      single cells using a pipette. The device is inexpensive and the method economizes
      time and labor. An example of its use in DNA double-strand breaks study, using
      microgel electrophoresis, is described.

PMID- 9515723
TI  - Cytochrome c in the apoptotic and antioxidant cascades.
AB  - Recent progress in studies on apoptosis has revealed that cytochrome c is a pro
      apoptotic factor. It is released from its places on the outer surface of the
      inner mitochondrial membrane at early steps of apoptosis and, combining with some
      cytosolic proteins, activates conversion of the latent apoptosis-promoting
      protease pro-caspase-9 to its active form. Cytochrome c release can be initiated
      by the pro-apoptotic protein Bax. This process is blocked by the anti-apoptotic
      proteins Bcl-2 and Bcl-xL. The role of cytochrome c in apoptosis may be
      understood within the framework of the concept assuming that the evolutionary
      primary function of apoptosis was to purify tissues from ROS-overproducing cells.
      In this context, the pro-apoptosis activity of cytochrome c might represent one
      of the anti-oxidant functions inherent in this cytochrome. Among other cytochrome
      c-linked antioxidant mechanisms, the following systems can be indicated. (1)
      Cytochrome c released from the inner mitochondrial membrane to the intermembrane
      space can operate as an enzyme oxidizing O2.- back to O2. The reduced cytochrome
      c is oxidized by cytochrome oxidase (or in yeasts and bacteria, by cytochrome c
      peroxidase). (2) The intermembrane cytochrome c can activate the electron
      transport chain in the outer mitochondrial membrane. This bypasses the initial
      and middle parts of the main respiratory chain, which produce, as a rule, the
      major portion of ROS in the cell. (3) The main respiratory chain losing its
      cytochrome c is inhibited in such a fashion that antimycin-like agents fail to
      stimulate ROS production.

PMID- 9515724
TI  - Do transmembrane protein superfolds exist?
AB  - A reliable and widely used transmembrane protein structure prediction algorithm
      was applied to five representative genomic sequence data sets in order to re
      examine the hypothesis that in contrast to globular proteins there are no favored
      transmembrane protein fold families. When the number of predicted membrane
      spanning segments and the topology of these segments is taken into account then
      definite biases are observed which suggest that certain transmembrane topologies
      are significantly more common than others.

PMID- 9515725
TI  - Mild proteolysis induces a ready-to-fuse state on Sendai virus envelope.
AB  - The Sendai virus fuses with host cell membranes in a pH-independent manner
      through an unknown mechanism. Here we report that mild trypsin pre-treatments of
      Sendai virions, for example 15 min at 4 degrees C, give Sendai virions the
      ability to fuse at a rate up to 10-fold higher than control. By using human
      erythrocytes as host cell membranes, viral fusion was assessed by hemolysis as
      well as fluorescence dequenching of octadecyl rhodamine B chloride. The mild
      protease treatment strikingly shortens the lag time taken by the virus to start
      the fusion process. Similar data were obtained on reconstituted Sendai virus
      envelope. Among proteases, tested as fusion enhancer, trypsin is more effective
      than either endoproteinase Lys-C, chymotrypsin, or endoproteinase Arg-C. After
      removal of trypsin from treated virions the fusion rate enhancement remains for
      hours at room temperature. The lack of protease specificity, together with the
      impossibility to detect any new N-terminal products, suggests that only a small
      percentage of viral envelope components are cleaved, still a large enough number
      to set the envelope in a ready-to-fuse state.

PMID- 9515726
TI  - Two non-proline cis peptide bonds may be important for factor XIII function.
AB  - The structure of recombinant human cellular factor XIII zymogen was solved in its
      monoclinic crystal form and refined to an R-factor of 18.3% (Rfree = 23.6%) for
      all data between 40.0 and 2.1 A resolution. Two non-proline cis peptide bonds
      were detected. One is between Arg310 and Tyr311 close to the active site cysteine
      residue (Cys314) and the other is between Gln425 and Phe426 at the dimerization
      interface. The structure and the role of these cis peptides are discussed in the
      light of their possible importance for factor XIII function.

PMID- 9515727
TI  - Interaction of peroxynitrite with carotenoids and tocopherols within low density
      lipoprotein.
AB  - Peroxynitrite is a powerful oxidising and nitrating agent generated in vivo by
      the combination of nitric oxide and superoxide. Previous studies have shown that
      on exposure to peroxynitrite, low density lipoprotein (LDL) is modified resulting
      in both a time- and concentration-dependent change to lipid and protein
      components. The present investigation highlights the reaction between carotenoids
      and tocopherols, present within the lipophilic phase of LDL, and peroxynitrite at
      varying concentrations. It was observed that the carotenoids were consumed by a
      significantly greater proportion than that of the tocopherols with lycopene (87.2
      +/- 11%) being more reactive than beta-carotene (68.2 +/- 5.8%) when exposed to
      peroxynitrite (50 microM) for 1 min. Among the tocopherols, alpha-tocopherol
      (54.9 +/- 20.2%) was more extensively depleted than gamma-tocopherol (14.7 +/-
      1.09%) at peroxynitrite concentration of 500 microM. It was also observed that
      peroxynitrite, unlike copper ions, does not lead to significant peroxidation of
      LDL as determined by the formation of conjugated dienes and thiobarbituric acid
      reactive substances.

PMID- 9515728
TI  - Presence of leptin receptors in rat small intestine and leptin effect on sugar
      absorption.
AB  - Leptin is involved in food intake and thermogenesis regulation. Since leptin
      receptor expression has been found in several tissues including small intestine,
      a possible role of leptin in sugar absorption by the intestine was investigated.
      Leptin inhibited D-galactose uptake by rat small intestinal rings 33% after 5 min
      of incubation. The inhibition increased to 56% after 30 min. However, neither at
      5 min nor at 30 min did leptin prevent intracellular galactose accumulation. This
      leptin effect was accompanied by a decrease of the active sugar transport
      apparent Vmax (20 vs. 4.8 micromol/g wet weight 5 min) and apparent Km (15.8 vs.
      5.3 mM) without any change in the phlorizin-resistant component. On the other
      hand, immunohistochemical experiments using anti-leptin monoclonal antibodies
      recognized leptin receptors in the plasma membrane of immune cells located in the
      lamina propria. These results indicate for the first time that leptin has a rapid
      inhibitory effect on sugar absorption and demonstrate the presence of leptin
      receptors in the intestinal mucosa.

PMID- 9515729
TI  - DNA binding of polyomavirus large T-antigen: kinetics of interactions with
      different types of binding sites.
AB  - Polyomavirus large T-antigen binds to GRGGC sites in double-stranded viral DNA,
      regulating transcription and replication. Using surface plasmon resonance to
      record interactions of large T-antigen with different types of binding sites, we
      found that the configuration of recognition motifs influenced both the
      association and dissociation rates. Particularly, the complex formed at the
      origin of DNA replication was labile. A comparison of the interactions between
      large T-antigen and binding sites with one, two and four GRGGC motifs in tandem
      showed a strong preference for dimer binding, without detectable co-operativity
      between dimers. Sodium chloride stabilised the complexes, whereas the
      dissociation increased rapidly by increasing pH above 7.0.

PMID- 9515730
TI  - Diadenosine 5',5"-P1,P5-pentaphosphate harbors the properties of a signaling
      molecule in the heart.
AB  - Dinucleotide polyphosphates (ApnA) have emerged as signaling molecules in rapidly
      dividing cells. The presence and role of Ap5A in the heart remain unknown. Here,
      we report that the myocardium contains abundant amounts of diadenosine 5',5"
      P1,P5-pentaphosphate (Ap5A), a member of the ApnA family. Ischemia induced 10
      fold decrease in the myocardial concentration of Ap5A. A target of Ap5A action
      was identified to be the cardiac ATP-sensitive K+ (K(ATP)) channel, a metabolism
      sensitive ion conductance activated in ischemia. At levels found in hearts prior
      to ischemia, Ap5A maintained a low probability of K(ATP) channel opening, but at
      levels found in hearts following ischemia, Ap5A allowed a high probability of
      K(ATP) channel opening. Taken together, the present data suggest that Ap5A
      harbors the properties of a signaling molecule involved in the cardiac response
      to metabolic stress.

PMID- 9515731
TI  - Stability of plasminogen activator inhibitor-1: role of tyrosine221.
AB  - Using site-directed mutagenesis, changes of Tyr221 in plasminogen activator
      inhibitor-1 (PAI-1) have provided mutants with normal activity, but with
      increased stability. At physiological conditions, the transition of the PAI-1
      mutants Tyr221His and Tyr221Ser to the latent form was significantly prolonged
      (half-lives 14.8 and 4.1 h, respectively) as compared to wild-type PAI-1 (2.0 h).
      Their half-lives, especially for the Tyr221Ser mutant, were even more prolonged
      in the presence of vitronectin (23.8 and 53.7 h, respectively). While wild-type
      PAI-1 was more stable at lower pH, the PAI-1 mutants Tyr221His and Tyr221Ser had
      stability optima at about pH 6.5, but displayed shorter half-lives at pH 5.5.

PMID- 9515732
TI  - The wheat wcs120 promoter is cold-inducible in both monocotyledonous and
      dicotyledonous species.
AB  - The wcs120 gene is specifically induced by low temperature (LT) and encodes a
      protein that is thought to play an important role in the cold acclimation process
      in wheat. To identify the regulatory elements involved in its LT responsiveness,
      the transient expression activity of different promoter regions was determined
      using the luciferase reporter gene. The data indicate the involvement of putative
      enhancer elements, negative and positive regulatory regions in the
      transcriptional regulation of this gene. The promoter was found to be cold
      inducible in different freezing-tolerant and -sensitive monocot and dicot
      species, suggesting that universal transcription factors responsive to LT may be
      present in all plants. This promoter could be used to drive the genes needed for
      LT tolerance in sensitive species.

PMID- 9515733
TI  - Specific cation binding site in mammalian cytochrome oxidase.
AB  - Calcium ion binds reversibly with cytochrome c oxidase from beef heart
      mitochondria (Kd approximately 2 microM) shifting alpha- and gamma-absorption
      bands of heme a to the red. Two sodium ions compete with one Ca2+ for the binding
      site with an average dissociation constant square root[K1(Na) x K2(Na)]
      approximately 3.6 mM. The Ca2+-induced spectral shift of heme a is specific for
      mammalian cytochrome c oxidase and is not observed in bacterial or yeast aa3
      oxidases although the Ca2+-binding site has been revealed in the bacterial enzyme
      [Ostermeier, C., Harrenga, A., Ermler, U. and Michel, H. (1997) Proc. Natl. Acad.
      Sci. USA 94, 10547-10553]. As His-59 and Gln-63 involved in Ca2+ binding with
      Subunit I of P. denitrificans oxidase are not conserved in bovine oxidase, these
      residues have to be substituted by alternative ligands in mammalian enzyme, which
      is indeed the case as shown by refined structure of bovine heart cytochrome
      oxidase (S. Yoshikawa, personal communication). We propose that it is interaction
      of Ca2+ with the species-specific ligand(s) in bovine oxidase that accounts for
      perturbation of heme a. The Ca2+/Na2+-binding site may be functionally associated
      with the exit part of 'pore B' proton channel in subunit I of mammalian
      cytochrome c oxidase.

PMID- 9515734
TI  - The endothelial receptor tyrosine kinase tie-1 is upregulated by hypoxia and
      vascular endothelial growth factor.
AB  - The receptor tyrosine kinase tie-1 is essential for angiogenesis where it appears
      to have a role in vessel maturation. Here we have examined the effects of hypoxia
      and vascular endothelial growth factor (VEGF) on the level of tie-1 protein
      expressed in bovine aortic endothelial cells. Both hypoxia (2% O2) and VEGF were
      found to increase tie-1 in a time-dependent manner. Hypoxic induction was direct
      and effects of hypoxia and VEGF were not additive. Experiments with actinomycin D
      indicate that these activators regulate tie-1 at the transcriptional level.

PMID- 9515736
TI  - Quantitative model for the cooperative interaction of the bacteriorhodopsin
      molecules in purple membranes.
AB  - The trimeric, asymmetric and sequential model for the cooperative interaction of
      the bacteriorhodopsin molecules in purple membranes [Zs. Tokaji, Biophys. J. 65
      (1993) 1130-11341 is being extended in the paper. Analyses of data from
      absorption kinetic measurements with preexcitation and green background
      illumination, and photoselection measurements on oriented samples confirm the
      main features of this cooperative interaction and support the validity of the
      extended model. This model includes the observed heterogeneity of the non-excited
      state of the bacteriorhodopsin molecules in purple membranes, and the agreement
      with the data suggests that molecules in any other state than the
      bacteriorhodopsin ground state can alter the photocycle of their neighbors. The
      presented results seem to contradict other models for the cooperation of the
      bacteriorhodopsin molecules.

PMID- 9515735
TI  - Fatty acid-induced uncoupling of oxidative phosphorylation is partly due to
      opening of the mitochondrial permeability transition pore.
AB  - Addition of myristate at low concentration (30-60 nmol/mg protein) to energized
      rat liver mitochondria resulted in dissipation of the electric membrane potential
      which, in Ca2+-free media, could be partly reversed by carboxyatractyloside but
      not by cyclosporin A. In contrast, in mitochondria preloaded with Ca2+ this
      energy-dissipating effect of fatty acid was partly prevented or reversed by
      cyclosporin A or ADP. In sucrose media, myristate, but not the protonophore
      carbonyl cyanide m-chlorophenylhydrazone, induced swelling of Ca2+-loaded
      mitochondria which was inhibited by cyclosporin A and ADP. We conclude that long
      chain fatty acids may induce opening of the mitochondrial permeability transition
      pore not only because of their protonophoric effect mediated by mitochondrial
      anion carriers [Skulachev, V.P., FEBS Lett. 294 (1991) 158-162; Wieckowski, M.R.
      and Wojtczak, L., Biochem. Biophys. Res. Commun. (1997) 232, 414-417] but also by
      a direct interaction with the pore assembly.

PMID- 9515737
TI  - Conformational independence of N- and C-domains in ribosomal protein L7/L12 and
      in the complex with protein L10.
AB  - Isolated N- (1-37) and C-terminal (47-120) fragments of L7 protein, and
      pentameric (L7)4L10 complex were studied by NMR spectroscopy in solution. The
      results indicate that the dimer state of the 1-37 fragment with a helical hairpin
      conformation is identical to the N-terminal structure of the intact L7 dimer. The
      C-terminal domain of the L7 protein does not participate in (L7)4L10 complex
      formation. The overall motions of the L7 C-domains are essentially independent
      both in the L7 dimer and in the (L7)4L10 complex. Conformational motions on a
      millisecond time scale are detected in the (L7)4L10 complex. The possible
      relevance of these motions to the biological function of L7/L12 is discussed.

PMID- 9515738
TI  - Protein synthesis in mitochondria isolated from the trypanosomatid protozoan
      Crithidia fasciculata.
AB  - Evidence presented over the years in support of mitochondrial translation in
      trypanosomes, based largely on studies using differential inhibitors such as
      cycloheximide and chloramphenicol, remains controversial. I have studied
      endogenous mRNA-dependent translation in a mitochondrial fraction isolated from
      the trypanosomatid protozoan Crithidia fasciculata. By using pancreatic
      ribonuclease to inactivate contaminating cytosolic activity, I show that these
      mitochondria can conduct protein synthesis in their own right. The mitochondrial
      translational products differed from cytosolic products as judged by SDS-PAGE,
      and had sizes expected of some proteins encoded in the mitochondrial genome of C.
      fasciculata and other trypanosomatids. Some evidence is provided suggesting that
      the seat of translation might be the kinetoplast.

PMID- 9515739
TI  - Presence and localization of oscillin in human spermatozoa in relation to the
      integrity of the sperm membrane.
AB  - We investigated the presence and localization of oscillin in human spermatozoa in
      relation to the integrity of the sperm membrane, which was assessed by the hypo
      osmotic swelling (HOS) test. We found no gross differences in the presence of
      oscillin in semen samples from men who presented with 70%, 40%, 25% or 2% of
      membrane-intact spermatozoa. By immunofluorescence, membrane-intact (HOS
      positive) spermatozoa showed staining of a single band at the equatorial region,
      whereas over 80% of HOS-negative spermatozoa consistently showed a diffuse
      distribution of oscillin over the sperm head. However, some individuals presented
      with up to 50% of HOS-positive spermatozoa showing an aberrant localization of
      oscillin. We found a significant correlation rate (r=0.70, P < 0.05) between the
      percentage of HOS-positive spermatozoa with an equatorial oscillin localization
      and the fertilization rates achieved after intracytoplasmic sperm injection.
      These data suggest that the localization of oscillin in human spermatozoa might
      have an impact on egg activation and fertilization rates.

PMID- 9515740
TI  - CFTR mRNA and its truncated splice variant (TRN-CFTR) are differentially
      expressed during collecting duct ontogeny.
AB  - The collecting duct epithelium originates from the embryonic ureter by branching
      morphogenesis. Ontogeny-dependent changes of CFTR mRNA expression were assessed
      by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) in
      primary monolayer cultures of rat ureteric buds (UB) and cortical collecting
      ducts, microdissected at different embryonic and postnatal developmental stages.
      The amount of wild-type CFTR-specific PCR product in UB declined to 20% of the
      initial value between embryonic gestational day E15 and postnatal day P1. After
      birth the CFTR product increased transiently between P1 and P7 by a factor of 10
      and decreased towards day P14. PCR products specific for TRN-CFTR, a truncated
      splice variant, however, were low in early embryonic cells, increased markedly
      between day E17 and P2, and reached a plateau postnatally. Therefore, mRNA
      encoding TRN-CFTR does not appear to have a specific embryonic-morphogenetic
      function. By contrast, such function is suggested for wild-type CFTR mRNA as its
      abundance was high in early embryonic nephrogenesis, as well as during a
      postnatal period shortly before branching morphogenesis is completed.

PMID- 9515741
TI  - cDNA cloning and sequencing of the human ryanodine receptor type 3 (RYR3) reveals
      a novel alternative splice site in the RYR3 gene.
AB  - The human ryanodine receptor type 3 (RYR3) was cloned from a fetal brain cDNA
      library and its complete sequence was determined (EMBL accession number
      AJ001515). The sequenced cDNA spanned 15,564 bp and contained an open reading
      frame of 14,613 bp. The corresponding protein consisted of 4870 amino acids with
      a calculated molecular mass of 552 kDa. Amino acid sequence identities to the
      RYR3 proteins from rabbit, mink, and chicken were 96%, 95%, and 83% respectively.
      A previously unidentified alternative splice site was detected generating a
      transcript that lacked bases 11,569-11,650 and encoded a truncated protein.

PMID- 9515742
TI  - Changes in the periplasmic linker and in the expression level affect the activity
      of ToxR and lambda-ToxR fusion proteins in Escherichia coli.
AB  - In order to assess the potentiality of Vibrio cholerae ToxR protein and of
      bacteriophage lambda repressor as indicators of the dimerization of periplasmic
      proteins in Escherichia coli, we have constructed a series of plasmids encoding
      transmembrane fusion proteins. The amino-terminal part, containing the DNA
      binding domain of either ToxR or lambda repressor, is located in the cytoplasm
      and acts as reporter for dimerization. As models of periplasmic proteins we have
      used alkaline phosphatase (a dimer) and beta-lactamase (a monomer). Both the
      expression level and the distance between the transmembrane segment and the
      periplasmic protein substantially affect the activity of the reporter domains.

PMID- 9515743
TI  - MK-801 blocks monoamine transporters expressed in HEK cells.
AB  - (+)-MK-801 is known to be a specific non-competitive antagonist of N-methyl-D
      aspartate (NMDA) receptors. However, besides having an anticonvulsant effect,
      this compound possesses a central sympathomimetic effect and an anxiolytic-like
      action, raising the possibility that (+)-MK-801 might affect monoamine uptake
      systems. To elucidate this possibility, we investigated the effects of (+)-MK-801
      on monoamine transporters expressed in HEK cells. (+)-MK-801 significantly
      inhibited the uptake of all three monoamine transporters in a dose-dependent
      manner and the inhibitions were competitive with respect to monoamines. The Ki
      values of (+)-MK-801 on the norepinephrine, dopamine and serotonin transporters
      were 3.2 microM, 40 microM and 43 microM, respectively. In addition, (-)-MK-801,
      a less potent antagonist of NMDA receptors, also inhibited monoamine transporters
      with a similar potency as that of (+)-MK-801. These results clearly indicate that
      MK-801, a non-competitive antagonist of NMDA receptors, competitively inhibits
      monoamine transporters without stereoselectivity.

PMID- 9515744
TI  - Gastroenterology-hepatology in The Netherlands: a review of 12 years of
      highlights. Proceedings of a symposium. Jerez de la Frontera, Spain, April 24-27,
      1997.

PMID- 9515746
TI  - 13C breath test in gastroenterological practice.
AB  - Breath tests (BTs) are used in gastroenterological practice to study
      (patho)physiological and metabolic processes in an indirect way. In these tests
      the appearance in breath of a metabolite of a specific test substance is studied.
      The assumption underlying each BT is that one step-the process of interest-in the
      absorption and metabolism of the tracer is rate-limiting. Both hydrogen gas
      excretion and carbon dioxide appearance in breath can be studied. When a carbon
      labelled test substance is used. the stable isotope 13C is preferred to the
      radioactive isotope 14C. Measurements of 13C in expired air are performed by mass
      spectrometry. Because of the indirect nature of BTs, involving a sequence of
      reactions and metabolic pools, they usually supply semiquantitative data. The
      tests are nevertheless useful because they often replace invasive techniques with
      a simple procedure that is safe because there is no radioactivity involved. BTs
      have been used to measure gastric emptying, the presence of Helicobacter pylori
      in the stomach, small-bowel bacterial overgrowth, exocrine pancreatic function as
      well as liver metabolic capacity; other potential applications of BTs are being
      studied.

PMID- 9515745
TI  - Occlusive and non-occlusive gastrointestinal ischaemia: a clinical review with
      special emphasis on the diagnostic value of tonometry.
AB  - BACKGROUND: To review clinical features of the occlusive splanchnic ischaemia
      syndromes with special emphasis on the diagnostic value of tonometry. METHODS:
      The English literature was reviewed with an emphasis on papers concerning anatomy
      and physiology of splanchnic perfusion, the clinical presentation and diagnostic
      procedures in occlusive splanchnic ischaemia syndromes. RESULTS: Splanchnic
      ischaemia can result from hypovolaemic states, resulting in splanchnic
      vasoconstriction and ischaemia with normal splanchnic vessels (non-occlusive
      ischaemia) or from vascular stenoses (occlusive ischaemia). The former is
      frequently encountered in critically ill patients, whereas the latter is
      considered rare, despite a relatively high incidence of splanchnic
      atherosclerosis. The main problem hindering assessment of the incidence of
      symptomatic chronic splanchnic ischaemia is the lack of a diagnostic procedure
      separating symptom-free from symptomatic splanchnic atherosclerosis. Although
      angiography provides precise anatomical information, the correlation with
      symptoms is poor. From various studies it emerges that tonometry of luminal PCO2
      enables assessment of ischaemia. CONCLUSIONS: Splanchnic ischaemia may be more
      common than currently assumed, but a gold standard diagnostic tool is lacking.
      Tonometry of the gastric PCO2 may be the most promising technique for detecting
      and grading splanchnic ischaemia.

PMID- 9515747
TI  - Gastric asthma: a pathophysiological entity?
AB  - BACKGROUND: Gastro-oesophageal reflux disease (GORD) is manifested by typical
      reflux symptoms and atypical extra-oesophageal symptoms. Important in this
      respect are respiratory conditions. Gastric asthma is a prominent example of
      these extra-oesophageal manifestations of GORD. There is, however, much debate
      about its prevalence, pathophysiology and clinical importance. METHODS: Narrative
      review of the literature. RESULTS: In asthmatics, the prevalence of GORD is
      generally reported to be higher than in normals, but with a wide range, probably
      due to patient selection. In a minority of asthmatics GORD aggravates or triggers
      asthma. The pathogenetic mechanisms can be a vagally transmitted reflex as well
      as micro-aspiration of refluxed material. The association with inflammatory
      mediator release has been insufficiently investigated. Selecting those who are
      likely to respond to anti-reflux measures is important: those with difficult to
      treat asthma, non-allergic asthma, adult-onset asthma with GORD. Oesophageal pH
      metry to prove GORD and gastroscopy to diagnose Barrett's metaplasia are
      advisable.

PMID- 9515748
TI  - Otolaryngologic manifestations of gastro-oesophageal reflux disease.
AB  - At present, gastro-oesophageal reflux disease (GORD) is believed to be an
      important contributing etiologic factor in many laryngopharyngeal disorders.
      Endoscopic oesophagitis, however, is found in less than 25% of these patients.
      Prolonged oesophageal pH monitoring with a dual pH probe is the most sensitive
      test for diagnosing GORD-related ear, nose and throat (ENT) problems. Based on
      the therapy studies one may recommend the use of, preferably, proton-pump
      inhibitors in higher doses than in typical GORD patients. Therapy may be
      necessary for prolonged intervals or for a lifetime.

PMID- 9515749
TI  - Is there a place for laparoscopic antireflux surgery in The Netherlands?
AB  - BACKGROUND: Antireflux surgery has not gained wide acceptance in The Netherlands
      in the past two decades. The introduction of laparoscopic fundoplication seems to
      have had no impact on the number of antireflux operations performed per year.
      METHODS: The SIG data were consulted in order to compile an inventory on the
      number of antireflux operations performed in The Netherlands between 1977 and
      1995. The data were compared with those kindly supplied by the Laparoscopic
      Societies of the Scandinavian countries. RESULTS: The number of antireflux
      operations per year in The Netherlands, 1.7/100,000 per year, is far less than
      reported in the four Scandinavian countries, 15/100,000 per year, and also far
      below the 10/100,000 per year needed for antireflux surgery on a yearly basis.
      CONCLUSIONS: In The Netherlands, 1.7/100,000 inhabitants per year undergo
      antireflux surgery. This figure has remained virtually stable in the past two
      decades, i.e. it has not changed even since the introduction of H2-receptor
      antagonists, proton-pump inhibitors and laparoscopic antireflux surgery. The
      success of medical treatment and personal, anecdotal, experience of
      gastroenterologists with patients they have referred for surgery explain the low
      number of antireflux operations performed. Currently, a randomized trial is being
      conducted in The Netherlands comparing the effectivity, costs and quality of life
      after conventional Nissen fundoplication with the laparoscopic approach. All
      operations are performed or supervised by a limited number of experienced
      surgeons who have gone through the learning curve of both the open and
      conventional technique.

PMID- 9515750
TI  - Is the sensitivity to gastric acid inhibition Helicobacter pylori status
      dependent?
AB  - BACKGROUND: Recent studies using 24-h intragastric pH monitoring suggest that
      treatment with a proton-pump inhibitor is less effective in Helicobacter pylori
      negative than in H. pylori-positive subjects. AIM: To survey and discuss the
      available information on the interaction between H. pylori status and the
      sensitivity to inhibition of gastric acid secretion. METHODS: Literature review.
      RESULTS: Upon cure of the infection in H. pylori-positive subjects (healthy
      controls and duodenal ulcer patients), the effect of omeprazole on gastric pH
      decreases significantly. The findings indicate that H. pylori or H. pylori
      related gastritis augments the sensitivity to proton-pump inhibitors. Preliminary
      information suggests that the sensitivity to H2-receptor antagonists might be
      less dependent on H. pylori status. The mechanisms through which H. pylori or the
      H. pylori-associated gastritis leads to increased sensitivity to acid inhibition
      have not been fully elucidated. It has been hypothesized that the gastritis
      associated with H. pylori infection plays a role, since the mucosal inflammatory
      infiltrate can release acid inhibitory cytokines. Another possible mechanism
      involves the production of acid neutralizing substances by H. pylori, in
      particular ammonia. Ammonia might also interfere with the activity of the H+/K+
      ATPase pump. Finally, H. pylori has been shown to produce fatty acids that
      inhibit the proton pump. CONCLUSIONS: An interaction exists between H. pylori
      status and sensitivity to acid inhibition. This interaction has important
      clinical implications. In H. pylori-negative patients, current dosing with a
      proton-pump inhibitor may result in insufficient acid control for optimal
      treatment of gastro-oesophageal reflux disease (GORD). In future studies on
      treatment and the natural course of GORD, H. pylori status must be taken into
      account.

PMID- 9515751
TI  - New options in Helicobacter pylori eradication: efficacy, resistance and synergy.
AB  - The eradication of Helicobacter pylori has become the focus of much attention
      since the first attempts at developing effective therapies some 10 years ago.
      This review focuses on ranitidine bismuth citrate (RBC), the first new drug to be
      introduced for use in the eradication of H. pylori. RBC when combined with
      clarithromycin gives consistently high eradication rates (above 80% intention-to
      treat assessment in double-blind, international studies) as a simple dual therapy
      for 14 days or when combined with two antibiotics as a triple therapy for 7 days.
      RBC enhances the in vitro killing of H. pylori by antibiotics, such as
      clarithromycin, metronidazole or tetracycline, in a synergistic manner. This
      effect is seen even when the H. pylori strains are 'resistant' to the
      antibiotics. Such a synergistic effect probably explains the increased efficacy
      of RBC-clarithromycin dual therapies compared with clarithromycin dosed with acid
      suppressive agents such as H2-receptor antagonists or proton-pump inhibitors.

PMID- 9515752
TI  - The constipated stomach. An underdiagnosed problem in patients with abdominal
      pain?
AB  - The number of dyspeptic patients with upper abdominal pain that are referred for
      investigation is increasing and will undoubtedly continue to increase, because
      these days peptic ulcer disease is increasingly becoming a primary care
      management issue, the specialist being left to deal with the patients who cannot
      be helped by antibiotics and antisecretory drugs prescribed by their general
      practitioner. Many of these patients are referred for an upper endoscopy to rule
      out organic disease. Carefully taken history, however, shows that a great number
      of those dyspeptics, on the basis of their clinical manifestations, do have a
      functional gastrointestinal disorder, representing the 'irritable gut'. A
      probable better term reflecting the direct relation is the syndrome of 'the
      constipated stomach'. In our opinion these patients are an important and
      increasing clinical problem for general practitioners, gastroenterologists,
      surgeons and physicians. The aim of this article is to make the practitioner
      aware of advancements in understanding pathophysiologic and psychosocial
      processes, as well as to give an overview of the great overlap between many
      functional gastrointestinal disorders, the important role of history-taking and
      some insights into the functional rectal outlet syndrome.

PMID- 9515753
TI  - Gastrointestinal motility after pancreatoduodenectomy.
AB  - Pancreatoduodenectomy (PD) is a major surgical procedure which is accompanied by
      a high morbidity of between 30 and 50%. A large part of this morbidity is caused
      by delayed gastric emptying (DGE), which is reported to have an incidence of
      between 30 and 40% and is associated with prolonged hospital stay. Several
      pathophysiological mechanisms are thought to cause this complication.
      Peroperative trauma of the pylorus and the occurrence of intra-abdominal
      abscesses play a role. Neuronal changes and disruption of the gastrointestinal
      (GI) intramural nervous plexus may be especially important regarding the pivotal
      role of the duodenum in the initiation and coordination of antroduodenal motor
      activity. Another important factor is the postoperative administration of enteral
      nutrition. Recently, it was demonstrated that cyclic enteral nutrition through a
      catheter jejunostomy led to a faster return to normal diet and shorter hospital
      stay than patients on continuous enteral nutrition; this might be partly caused
      by continuously elevated cholecystokinin levels. The effect of prokinetic agents
      has not been studied extensively, but a beneficial action on the return of
      postoperative gastric function after gastrointestinal surgery seems limited.

PMID- 9515755
TI  - Autoimmune hepatitis: pathogenesis, diagnosis and treatment.
AB  - BACKGROUND: Autoimmune hepatitis (AIH) is a chronic necro-inflammatory disease of
      the liver. Early recognition is important in order to prevent the development of
      cirrhosis. This review discusses recent developments in the fields of diagnosis,
      pathophysiology and management of AIH. METHODS: Relevant manuscripts were
      identified using an electronic database, and by hand search of a personal
      library. RESULTS AND CONCLUSIONS: Description of new auto-antibodies, and
      formulation of diagnostic criteria and a scoring system by an international panel
      constitute important advances that may help diagnosis of the disease at an early
      stage. While a satisfying animal model of the disease is lacking, clinical
      observations have led to the formulation of a pathophysiological model. Current
      treatment has a failure rate of about 13%, and is unable to induce a permanent
      remission in most patients. New immunosuppressive agents (cyclosporine,
      tacrolimus and mycophenolate mofetil) appear promising, and should be evaluated
      in controlled trials.

PMID- 9515754
TI  - Endoscopic dilatation of the biliary sphincter for removal of bile duct stones:
      an overview of current indications and limitations.
AB  - Endoscopic balloon dilatation (EBD) of the biliary sphincter may be an
      alternative to endoscopic sphincterotomy (EST) for removal of bile duct stones.
      After EBD of the biliary sphincter to a diameter of 8 mm, stones are removed
      according to standard guidelines. In the event that stone removal fails after
      EBD, an additional EST is performed. The overall success rate of stone removal
      after EBD (90%) is comparable to that of EST. After EBD, an additional EST and
      mechanical lithotripsy are required in 10% and 30% of patients, respectively. In
      patients with bile duct stones < 10 mm and a stone number < or = 3, EBD is nearly
      always successful without the need for additional EST or mechanical lithotripsy.
      Pancreatitis post-EBD occurs at a rate of 5-7%, which is not significantly
      different from that after EST. Significant bleeding post-EBD has not been
      observed in over 400 patients undergoing EBD. EBD is a valuable alternative to
      EST, especially in patients with smaller bile duct stones and in patients with
      haemostatic disorders.

PMID- 9515756
TI  - Alcohol consumption and alcohol-related liver disease in The Netherlands.
AB  - BACKGROUND: No data have so far been published concerning the extent of the
      problem of alcohol-related liver diseases in The Netherlands. METHODS: Figures on
      alcohol consumption and admission and mortality rates due to alcohol-related
      liver disorders in The Netherlands in 1994 were obtained from various sources and
      the data were considered in a historical perspective. Special attention was paid
      to regional differences. RESULTS: The per capita alcohol consumption in 1994 in
      The Netherlands was 86 litres of beer, 16 litres of wine and 1.8 litres of pure
      alcohol as spirits. The total alcohol per capita consumption of individuals
      upwards of 15 years of age showed a decrease from 11.7 litres in 1975 to 9.7
      litres in 1994. In the same period the estimated number consuming more than 10 cl
      pure alcohol (8 units) per day remained at about 180,000. The number of general
      hospital admissions as a result of alcohol-related liver disease as well as the
      number of deaths because of cirrhosis has hardly changed since 1985. In 1994, 657
      men and 407 women were admitted due to alcohol-related liver disease, and 269 men
      and 125 women died from an alcohol-related liver disorder. The admission and
      mortality rates from alcohol-related liver disease differed markedly among the
      various provinces of The Netherlands.

PMID- 9515757
TI  - Palliation of malignant dysphagia from oesophageal cancer. Rotterdam Oesophageal
      Tumor Study Group.
AB  - Palliative therapies for advanced oesophageal cancer include surgery, radiation
      therapy, chemotherapy, endoscopic procedures and combinations of these. Of the
      non-endoscopic modalities is external beam radiation therapy (EBRT) effective and
      non-invasive. A disadvantage is that relief of dysphagia only occurs over a
      period of 4-6 weeks. Brachytherapy is more rapid in locally controlling tumour
      growth and in relieving dysphagia. One of the more commonly used endoscopic
      procedures is laser therapy, which provides symptomatic relief with low
      complication rates. Recurrent dysphagia is a problem necessitating repeated
      treatment sessions. Self-expanding metal stents offer a high degree of palliation
      and are associated with fewer complications compared with prosthetic tubes.
      Longer palliation and perhaps even longer survival might be achieved by the
      combination of different therapies. Most promising are the combination of EBRT
      plus brachytherapy or chemoradiation. Now is the time to determine which
      treatment (combination) is best for individual patients.

PMID- 9515758
TI  - Extracolonic manifestations of familial adenomatous polyposis: desmoid tumours,
      and upper gastrointestinal adenomas and carcinomas.
AB  - It is well known that patients with familial adenomatous polyposis (FAP) are at
      considerable risk of developing extracolonic manifestations of the disease.
      Particularly, desmoid tumours of the abdominal cavity, and duodenal adenomas and
      carcinomas are the most serious ones. It is estimated that some 10% of the FAP
      patients will develop desmoids, whereas 50-90% of the FAP patients will get
      duodenal adenomas predominantly concentrated on or around the major papilla.
      Desmoid tumours and duodenal carcinomas are major causes of death in those
      patients in whom a prophylactic (procto)colectomy has been performed. Desmoids
      are histologically benign tumours, composed of mature fibroblasts. They usually
      grow slowly but they can become quite large and may compress or infiltrate
      surrounding viscera, which might cause significant morbidity as well as
      mortality. Successful treatment of these tumours is extremely difficult as
      surgical therapy often requires the removal of considerable lengths of small
      bowel. Moreover, surgical therapy may lead to uncontrollable bleeding and is
      seldom radical. Chemotherapy with cytoxic agents seems promising but so far the
      data are too few for firm conclusions to be drawn. The same holds true for drug
      regimens which interfere with the metabolic and hormonal metabolism of the
      tumour. Although various lines of evidence suggest that the adenoma-carcinoma
      sequence, which is generally accepted for colorectal adenomas, also applies for
      the duodenal adenomas in FAP patients, it is not clear whether we should screen
      these patients for upper gastrointestinal adenomas or not. As these polyps are
      usually small, sessile, multiple and difficult to remove, the benefit of
      endoscopic surveillance would be the early detection of cancer rather than
      eradication of the polyps. In addition, evidence that screening and early
      treatment leads to improvement of the prognosis is not available. Although the
      role of (procto)colectomy in the treatment of large-bowel polyps is well
      established in FAP patients, the treatment of their duodenal counterparts is
      still open for debate. The risk of the development of periampullary cancer is not
      high enough to warrant an aggressive prophylactic surgical approach, i.e. a
      Whipple's procedure, immediately after the discovery of duodenal adenomas. The
      considerable morbidity and mortality rates of this procedure must be weighted
      against a putative benefit of screening.

PMID- 9515759
TI  - Azathioprine: state of the art in inflammatory bowel disease.
AB  - INTRODUCTION: The use of 6-mercaptopurine (6MP) and its prodrug azathioprine
      (AZA) for inflammatory bowel disease (IBD) has increased in recent years. The
      pharmacology, patient response in controlled trials, new formulations and routes
      of administration and safety for these agents are reviewed. PHARMACOLOGY: AZA is
      rapidly converted to 6MP, which is then further metabolized to the active
      metabolites, the 6-thioguanine nucleotides (6TGN). The half-life of 6TGN in
      erythrocytes is prolonged and weeks to months may be required to reach steady
      state. This prolonged time to 6TGN steady state may help explain the clinical
      observation that prolonged treatment (3-4 months) with 6MP/AZA for IBD is
      required before a therapeutic response occurs. CLINICAL RESPONSE: Controlled
      trials of 6MP (1.5 mg/kg/d) or AZA (1.0-3.0 mg/kg/d) support the following
      treatment indications for 6MP/AZA: inflammatory Crohn's disease; fistulizing
      Crohn's disease; steroid-sparing; and remission maintenance. Controlled trials of
      AZA (1.5-2.5 mg/kg/d) in UC have suggested efficacy for the indications of
      steroid sparing and remission maintenance, as well as a possible effect in
      chronically active disease. A therapeutic response appears to require > or = 17
      weeks for most patients, and it has been suggested that a greater cumulative dose
      of AZA may result in increased likelihood of response to AZA. A recent pilot
      study suggested that administration of an i.v. loading dose of AZA (20-44 mg/kg
      over 36 h) may decrease the time to response in Crohn's disease patients treated
      with AZA, perhaps by administering a portion of the necessary cumulative dose
      more rapidly. Two recent pharmacokinetic studies demonstrated that use of a
      delayed release oral AZA formulation which delivers AZA directly to the ileocolon
      markedly reduces systemic absorption of AZA. This 'topical' or 'local' approach
      to AZA treatment of IBD holds the promise of equal or improved efficacy with a
      significant reduction in toxicity, and dose-ranging clinical trials with delayed
      release oral AZA are planned in the near future. SAFETY: Side effects of AZA/6MP
      include pancreatitis, fever, nausea, leukopenia, infection, and hepatitis. It
      appears that the risk of malignancy during or following monotherapy with AZA/6MP
      for IBD is not increased relative to the general population. CONCLUSIONS: AZA/6MP
      therapy is efficacious and reasonably safe for selected patients with IBD.
      Indications for treatment with AZA/6MP include refractory Crohn's disease,
      fistulizing Crohn's disease, steroid-dependent Crohn's disease, Crohn's disease
      remission maintenance, and possibly refractory UC, steroid dependent UC, and UC
      remission maintenance. The use of these immune modifier drugs in patients with
      IBD represents a significant therapeutic advance.

PMID- 9515760
TI  - Crohn's disease of the upper gastrointestinal tract: the value of endoscopic
      examination.
AB  - The involvement of the upper gastrointestinal (GI) tract has been considered to
      be a rare manifestation of Crohn's disease (CD). Retrospective studies have
      reported prevalence figures of 0.5-13%. The diagnosis of CD of the upper GI tract
      is based on clinical, radiological, endoscopic and histologic features. In
      contrast to the retrospective studies, prospective studies, in which patients
      with CD underwent routine endoscopic evaluation with biopsies, revealed a much
      higher frequency of endoscopic and histologic abnormalities. Since Helicobacter
      pylori is the most frequent cause of gastritis and the most important etiologic
      factor in peptic ulcer disease, it is important to assess the contribution of H.
      pylori in the interpretation of the abnormalities observed in the upper GI tract
      in patients with CD. Therapy for CD of the upper GI tract consists of drug
      therapy and endoscopic or surgical interventions and is in fact similar to that
      for distal CD. Corticosteroids are still the most important drugs in the
      treatment of CD of the upper GI tract. Sometimes adjunctive therapy, e.g. gastric
      antisecretory drugs and mucosa protective agents, is beneficial. Endoscopic
      evaluation of the upper GI tract with biopsies should be part of the work-up of
      CD patients.

PMID- 9515761
TI  - Investigation of vesicular rashes for HSV and VZV by PCR.
AB  - Vesicular fluid from rashes of 132 patients was tested by a multiplex PCR shown
      to be specific for herpes simplex virus (HSV) type 1 and 2, and varicella zoster
      virus (VZV) genomic DNA. The results were compared with those obtained by
      examination by electron microscopy and virus isolation by cell culture. The PCR
      did not differentiate between HSV 1 and 2. By PCR, 64 HSV infections and 53 VZV
      infections were identified, with presumed 100% sensitivity and specificity.
      Fifteen specimens tested negative by PCR, electron microscopy, and virus
      isolation for herpes viruses. The sensitivities of virus isolation and electron
      microscopy for detection of herpes simplex virus were 56% and 80%. For varicella
      zoster virus, the sensitivities of virus isolation and electron microscopy were
      47% and 60%. These data illustrate the advantage of rapid PCR diagnosis of herpes
      simplex virus and varicella zoster virus in vesicle fluids.

PMID- 9515762
TI  - Herpes simplex virus-1 and varicella virus infections in familial dysautonomia
      patients.
AB  - Familial dystautonomia (FD) patients are deficient in type C fibers, suggesting
      that there may be a different pattern of infection and clinical presentation when
      infected by Herpes simplex virus type 1 (HSV-1) or Varicella-Zoster virus (VZV).
      These viruses infect and are reactivated in the periphery of the body through
      type C sensory nerve fibers. HSV-1 infects epithelial cells, penetrates into type
      C fibers, and migrates to the ganglia to generate latent infection. In
      reactivation, the viral DNA migrates through type C fibers, infecting the
      epidermis at the entry site. VZV infects through the respiratory tract, causing
      systemic viral infection and latency in the ganglia, from which it is reactivated
      and reaches the skin. The study was carried by clinical questionnaire and by HSV
      and VZV IgG antibodies on fifty-one FD patients and eighty matched controls. The
      questionnaire revealed that no FD patient had a history of clinical HSV-1
      infection, compared to 15% in the control group (P < 0.05), while 50% FD patients
      had been infected by varicella, compared to 66% in the VZV control group. However
      in FD, VZV clinical manifestations were mild in comparison to controls. There was
      no difference in infection rates for some other viral diseases. HSV-1 antibodies
      were detected in 24% of the FD patients, compared to 38% in the control group (P
      < 0.1). VZV antibodies were similar in FD and controls (66%, 63%). We concluded
      that the rate of HSV infection in FD is low and clinical reactivation is rare.
      The rate of varicella infection appears to be the same for patients and controls,
      but in FD the clinical presentation is mild. We suggest that these differences
      are due to the lack of type C fibers in FD patients.

PMID- 9515763
TI  - Reactivation of herpes simplex virus type 1 in patients with Bell's palsy.
AB  - Reactivation of herpes simplex virus type 1 (HSV-1) has been implicated in the
      pathogenesis of idiopathic peripheral facial palsy (Bell's palsy). The present
      study used the polymerase chain reaction (PCR) to analyze the saliva of patients
      with Bell's palsy for the presence of shed HSV-1. The study involved 47 patients
      with Bell's palsy, 24 patients with Ramsay Hunt syndrome, and 16 healthy HSV
      seropositive volunteers. HSV-1 DNA was not detected in the saliva samples from
      HSV-seronegative patients. The prevalence of shed HSV-1 in patients with Bell's
      palsy (50%) was significantly higher than that in healthy volunteers (19%,
      p<0.05). When saliva samples were tested within 7 days after the onset of palsy,
      the prevalence of shed HSV-1 in patients with Bell's palsy (40%) was
      significantly higher than that in patients with Ramsay Hunt syndrome (7%,
      p<0.05). Furthermore, HSV-1 usually became undetectable by the second week after
      the onset of Bell's palsy when HSV-1 was detected during the acute phase of the
      disease. These findings strongly suggest that reactivation of HSV-1 is involved
      in the pathogenesis Bell's palsy, and indicate that PCR is a useful tool for
      early diagnosis of HSV-1 reactivation in patients with Bell's palsy.

PMID- 9515764
TI  - Tumor necrosis factor alpha promoter polymorphism at position -238 is associated
      with chronic active hepatitis C infection.
AB  - Tumor necrosis factor alpha (TNF-alpha) is involved in the pathogenesis of
      chronic hepatitis C virus infection. The gene for TNF-alpha is encoded in the
      major histocompatibility locus (MHC). Two polymorphisms at positions -308 and 
      238 in the TNF-alpha promoter region might influence TNF-alpha expression. These
      promoter polymorphisms have been linked previously to a number of infectious
      diseases. TNF-alpha promoter polymorphisms at positions -238 and -308 were
      studied by DNA sequencing and sequence-specific oligonucleotide hybridization in
      82 individuals with chronic hepatitis C and 99 control subjects. Subjects had
      been HLA class I and class II typed in a previous study. The frequency of the
      TNF238.2 promoter allele was significantly higher in the hepatitis C group
      (18.7%) compared to the controls (3.5%; P < 0.0001; pcorr < 0.009). No
      significant differences in the frequency of the TNF308.2 allele were observed
      between patients and controls. The increased frequency of the TNF238.2 allele
      could not be explained by linkage disequilibrium to HLA-B or -DR genes. These
      findings show an association between the TNF238.2 promoter variant and chronic
      active hepatitis C. They suggest that this polymorphism or a linked gene may be a
      host factor contributing to the development of chronic active hepatitis C.

PMID- 9515765
TI  - Association of hepatitis E virus with an outbreak of hepatitis at a military
      training camp in Nepal.
AB  - From 29 January 1995 to 15 March 1995, an outbreak of hepatitis occurred among
      692 soldiers at an isolated training camp 25 km east of Kathmandu. Thirty-two
      cases occurred approximately 8 weeks after arrival of soldiers at the camp. To
      determine the etiology of the outbreak, patient sera were examined for evidence
      of infection with hepatitis A, B, C, and E viruses using commercially available
      enzyme-linked immunosorbent assay (ELISA) kits. The polymerase chain reaction
      (PCR) was used to detect hepatitis E virus (HEV) RNA. Evidence of recent
      infection (IgM to HEV and/or HEV RNA) was found in all but two patients, whereas
      none had evidence of recent infection with hepatitis A, B, or C viruses.
      Therefore, the outbreak was attributed to HEV. Fecally contaminated drinking
      water was suspected as the source of the outbreak. To determine the extent of HEV
      infections among those without clinical hepatitis, sera from the remaining
      soldiers were examined for markers of HEV infection. Evidence of past infection
      (IgG to HEV in the absence of IgM or HEV RNA) was found among 204 soldiers
      (prevalence = 30%), leaving 488 individuals susceptible to infection at the onset
      of the outbreak. Evidence of recent infection was found among another 83
      individuals. We conclude that most exposed, susceptible soldiers sustained HEV
      infection without experiencing overt hepatitis. If the levels of virus inoculum
      and prior immunity in this population were typical, inapparent infection may be
      the usual adult response to virus exposure in an endemic area.

PMID- 9515766
TI  - Detection of human papilloma virus DNA in lymph nodes extirpated at radical
      surgery for cervical cancer is not predictive of recurrence.
AB  - In women with recurrent cervical cancer after radical surgery, lymph node
      metastasis is detectable histologically at the time of surgery in only about 50%
      of cases. The present study was designed to determine whether the detection of
      human papilloma virus (HPV) DNA in lymph nodes extirpated at operation, as an
      indication of micrometastasis, is predictive of recurrence. Using polymerase
      chain reaction (PCR), a total of 140 lymph nodes from 31 patients with HPV 16 DNA
      positive primary cervical tumours were tested for the presence of an HPV 16
      LCR/E6 gene fragment. HPV 16 DNA was detected in extirpated lymph nodes in 75%
      (6/8) of patients with recurrence (and who died within 5 years after surgery) and
      in 70% (16/23) of recurrence-free patients. In only four of the patients with
      recurrence (three of whom had HPV 16 DNA positive lymph nodes) was metastasis
      detectable histologically at surgery. HPV DNA positive lymph nodes were found in
      91% (10/11) of patients with histologically detectable metastasis at surgery and
      in 60% (12/20) of patients without metastasis. It is concluded that the presence
      of HPV DNA in extirpated lymph nodes at cervical cancer operation does not appear
      to be predictive of tumour recurrence.

PMID- 9515767
TI  - Human papillomavirus DNA sequences and p53 over-expression in laryngeal squamous
      cell carcinomas in Northeast China.
AB  - One-hundred-two patients with laryngeal squamous cell carcinomas in Northeast
      China were examined for human papillomavirus (HPV) DNA by the polymerase chain
      reaction (PCR) coupled with Southern blot hybridization, and for p53 over
      expression by immunohistochemical staining. HPV DNAs were found in 60 cases
      (58.8%). HPV-16, -18, -6, -11, and -33 DNAs were detected in 30 cases, 22 cases,
      25 cases, two cases, and one case, respectively. In addition, coinfection either
      with HPV-6 and -16 or with HPV-6 and -18 was detected in 20 cases (33.3% of HPV
      DNA-positive cases). p53 over-expression was observed in 60 patients (58.8%). p53
      was over-expressed significantly in the poorly-differentiated SCC and in patients
      with metastasis to lymph nodes (P < 0.05, respectively). Both HPV DNA and p53
      expression were positive in 35 patients, and negative in 17 patients. Either HPV
      DNA or p53-expression were positive in 50 patients (25 cases each). Although p53
      was detected in 35 (58.3%) of HPV-positive patients, there was no significant
      correlation between HPV infection and p53 over-expression in laryngeal squamous
      cell carcinomas of Northeast China.

PMID- 9515768
TI  - HPV 16 E7 antibody levels in cervical cancer patients: before and after
      treatment.
AB  - Antibody response to HPV16 E7 oncoprotein may represent a marker of cervical
      cancer. A HPV16 GST-E7 fusion protein was used in a Western Blot assay to analyse
      the HPV16 E7 antibody response in 30 patients before and after treatment for
      cervical carcinoma (stage IIB or IIIB). Patients were treated with three courses
      of cisplatin/bleomycin therapy followed by surgery, or with surgery alone.
      Thirteen out of 30 patients had serum antibodies to HPV16 E7 antigen. Three
      months after chemotherapy little or no change in antibody titre was detected. In
      contrast, after surgery, a significant decrease in antibody titre was observed in
      9/10 patients. In two cases the titre declined to zero 3 and 9 months after
      treatment, respectively. These results confirm the usefulness of studying anti
      HPV16 E7 antibody profile in cervical cancer patients and suggest that the serum
      response correlates with tumour burden.

PMID- 9515769
TI  - Nucleic acid detection as a diagnostic tool in polyomavirus JC induced
      progressive multifocal leukoencephalopathy.
AB  - Procedures involved in the diagnosis of JC virus central nervous system infection
      range from detection of virus specific products in biopsy material to
      demonstration of viral DNA in cerebrospinal fluid by PCR. Despite the fact that
      PCR is the most sensitive method for the detection of virus in clinical
      specimens, diagnostic evaluation is increasingly difficult in view of the
      possible subclinical activation of persistent JCV infection in the central
      nervous system of high risk patients. Therefore, PML diagnosis by molecular
      detection of JCV DNA in biopsy material was compared with diagnosis by PCR on CSF
      of patients with and without PML. Evaluation of the diagnostic techniques
      revealed that stereotactic biopsy based PCR diagnosis at present combines speed
      and sensitivity with the highest specificity available. Although the non invasive
      technique of JCV detection in CSF by PCR is even more sensitive leading to
      detection of about 20 genome equivalents per 1 microl of CSF, the specificity of
      the method is limited by subclinical presence of JCV DNA in CSF of neurologically
      asymptomatic HIV infected patients. Additionally, autopsy proven PML cases
      remaining JCV negative in PCR on CSF become a common finding. Therefore, in cases
      where biopsy is not performed, diagnosis of PML can only be achieved in
      combination with neurological and radiological diagnosis.

PMID- 9515770
TI  - Comparison of a rapid culture method combining an immunoperoxidase test and a
      group specific anti-VP1 monoclonal antibody with conventional virus isolation
      techniques for routine detection of enteroviruses in stools.
AB  - In order to shorten the time required for the detection of enteroviruses in stool
      specimens, an 18-h immunoperoxidase test combining low-speed centrifugation and
      the use of a group specific anti-VP1 monoclonal antibody (5-D8/1, Dako) was
      developed. This rapid culture assay (RCA) was compared blindly to a conventional
      culture assay (CCA) on a panel of 180 children's stool specimens received for
      routine diagnosis of enterovirus infection. The same cell lines (human embryonic
      fibroblasts and KB continuous cell line) were used in both tests. Discrepancies
      in results were analysed by a PCR technique with primers located in a conserved
      part of the 5' non-coding region of the enterovirus genome. Fourteen specimens
      were positive and 158 were negative with both tests. Four samples were positive
      with the RCA yet negative with the CCA and 3 others showed the opposite pattern;
      an additional sample positive by RCA was uninterpretable by CCA due to bacterial
      contamination. Subsequent PCR testing of these 8 samples showed no discrepancies;
      all were positive. Using CCA as the reference, the sensitivity and specificity of
      RCA were 77.8 and 98% respectively. Kinetic studies using enterovirus isolates
      demonstrated that RCA was much more sensitive than CCA during the first three
      days of culture. These results further suggested that RCA sensitivity could be
      improved by a factor of at least 10 times by prolonging the incubation period by
      24 hr. With this change, the RCA assay described below is suggested as a rapid
      alternative to CCA for the routine diagnosis of enterovirus infection in stool
      specimens. When an identification at the serotype level is required, samples
      found positive using RCA could then be subjected to CCA.

PMID- 9515771
TI  - Tumor necrosis factor alpha levels in plasma and whole-blood culture in dengue
      infected patients: relationship between virus detection and pre-existing specific
      antibodies.
AB  - The pathogenesis of dengue hemorrhagic fever (DHF) is not well known, but the
      role of host factors has been suggested. The level of immunoreactive circulating
      and cell-generated tumor necrosis factor alpha (TNF alpha) was studied in 35
      patients with DHF; its relationship with virus isolation and/or genome detection
      by reverse transcription polymerase chain reaction (RT-PCR) and specific
      antibodies were detected by hemagglutination inhibition (HI). Large variation of
      TNF alpha plasma levels was obtained in dengue-infected patients at the same
      stage of the disease and at the same day after infection. Most of the patients
      (14 out of 17 patients) who displayed augmented spontaneous in vitro production
      of TNF alpha by heparinized whole-blood culture compared with controls also had
      elevated levels of TNF alpha in the plasma. The TNF alpha values in
      lipopolysaccharide and phytohemagglutinin heparinized whole-blood cultures were
      not higher in patients than in controls, but low TNF alpha levels were obtained
      in three out of 30 patients. An inverse correlation was observed between
      spontaneous in vitro TNF alpha production and viral replication, which raises the
      issue of the antiviral effect of TNF alpha in dengue infection. The results do
      not support the hypothesis of the role of antibody-dependent enhancement giving
      rise to increased viremic titers and production of TNF alpha in patients. The
      present study demonstrates the activation of the TNF alpha-producing cells in
      dengue-infected patients and suggests further investigation to define the
      mechanism and the role of TNF alpha in the pathogenesis of dengue virus
      infection.

PMID- 9515772
TI  - Treatment of severe laryngeal papillomatosis with intralesional injections of
      cidofovir [(S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine].
AB  - Respiratory papillomatosis is a rare and often severe disease, usually localized
      in the larynx. It may cause respiratory distress and even life-threatening
      obstruction of the airways. Treatment is generally based on the evaporation of
      the lesions with a CO2 laser, but microsurgery, cytotoxic and/or cytostatic
      drugs, interferons, and vaccines are also used. Cidofovir [(S)-1-(3-hydroxy-2
      phosphonylmethoxypropyl)cytosine] (HPMPC) was shown to suppress the growth of
      tumors induced by rabbit papillomavirus as well as human papillomavirus (HPV).
      The efficacy of cidofovir was assessed in 17 patients with severe respiratory
      papillomatosis. Cidofovir at a concentration of 2.5 mg/ml was injected directly
      in the different laryngeal papillomatous lesions during microlaryngoscopy under
      general anesthesia. Biopsies were taken before the treatment was started both for
      anatomopathology and viral typing. HPMPC kinetics in serum was monitored in three
      patients, the drug levels being determined by high-performance liquid
      chromatography. Complete disappearance of the papillomatosis was observed in 14
      patients. Four patients relapsed and were successfully treated again with
      cidofovir. Of the three remaining patients, one progressed while under treatment
      with cidofovir, after an initial marked response. One patient had a partial
      remission and remained stable for more than 1 year after the last injection. He
      had a very aggressive and extensive disease originally. Finally, one patient was
      lost to follow-up after four injections. Intratumoral injections of cidofovir for
      the treatment of severe laryngeal papillomatosis is a powerful new therapeutic
      approach for this disease. Treatment was well tolerated, and no significant side
      effects were noted.

PMID- 9515773
TI  - Enterovirus infections and enterovirus specific T-cell responses in infancy.
AB  - The development of enterovirus specific T-cell and antibody responses were
      examined in a cohort of 60 healthy infants at the ages of 3, 6, 9, and 12 months.
      By the age of 6 months, 68% of the infants had developed T-cell responses against
      enterovirus antigens by lymphocyte proliferation test, whereas only 30% had
      serological evidence of an enterovirus infection. By this age, only 7% of the
      infants had adenovirus specific T-cell responses and 3% had serologically
      verified adenovirus infection. Enterovirus specific T-cell responses correlated
      with the lack of enterovirus antibodies in cord blood and the number of sibs
      reflecting protection by maternal antibodies and the rate of exposures,
      respectively. T-cell responses cross-reacted between different enterovirus
      serotypes. The results show that enterovirus infections occur frequently in
      infancy and induce T-cell immunity. Cellular immunity may be a more sensitive
      indicator of neonatal enterovirus infections than antibodies.

PMID- 9515774
TI  - Fatal adenovirus infection associated with new genome type.
AB  - The first fatal case caused by the new genome type 7i is described in an 8-month
      old boy requiring long-term respiratory support who developed Reye's syndrome,
      acute respiratory distress, and bronchiolitis obliterans with fatal evolution.
      Adenovirus was detected in nasopharyngeal secretions and was persistently
      positive during hospitalization. IgM and IgG adenovirus antibody titers measured
      in serum by enzyme-linked immunoassay (EIA) were 1:32 and 1:800, respectively.
      Serum interleukins (IL) and interferons (IFN) measured by EIA were as follows: IL
      2, 110 pg/ml; IL-6, 300 pg/ml; IL-8, 7,000 pg/ml; TNF-alpha, 35 pg/ml, IL-1 and
      IL-4 undetectable, IFN-alpha 2,200 pg/ml, and IFN-gamma 700 pg/ml. Virologic
      studies showed that adenovirus isolated belonged to subgenus B, and digestion of
      viral DNA with Bam HI, Sma I, Bgl II, and Hind III identified the isolate as
      belonging to genome type 7i. Autopsy showed bronchiolitis obliterans with diffuse
      alveolar damage and perivenular fatty degeneration with polymorphonuclear
      infiltrates in the periportal spaces. The difficulty in obtaining adequate
      oxygenation with minimization of iatrogenic oxygen injury is discussed.

PMID- 9515775
TI  - Disseminated intravascular coagulation: pathophysiological mechanisms and
      manifestations.
AB  - Current concepts of the many complex pathophysiological mechanisms and clinical
      and laboratory manifestations of disseminated intravascular coagulation (DIC) are
      presented. Considerable attention has been devoted to interrelationships within
      the hemostasis system. Only by clearly understanding these extraordinarily
      complex pathophysiological interrelationships can the clinician and laboratory
      scientist appreciate the divergent and wide spectrum of often confusing clinical
      and laboratory findings in patients with DIC. Many therapeutic decisions are
      controversial and will remain so until more is published about specific
      therapeutic modalities and survival patterns. The future holds promise for not
      only newer antithrombotic agents, but also agents which will block, blunt or
      modify cytokine activity and the activity of vasoactive substances. Also, therapy
      must be highly individualized depending on the nature of DIC, age, etiology of
      DIC, site and severity of hemorrhage or thrombosis and hemodynamic and other
      clinical parameters.

PMID- 9515776
TI  - Antithrombin: its physiological importance and role in DIC.
AB  - Antithrombin (AT) is a single-chain glycoprotein in plasma and belongs to the
      family of the serpins. It is synthesized in liver parenchymal cells, and its
      plasma concentration is between 112-140 mg/L. AT is a unique inhibitor of the
      clotting system and neutralizes most of the enzymes generated during activation
      of the clotting cascade, especially thrombin, factors Xa and IXa. Equimolar,
      irreversible complexes are formed between AT and the enzymes. The interaction
      between AT and the activated clotting factors is at least 1,000-fold increased in
      the presence of heparins. Heparins bind to multiple sites of the AT molecule
      resulting in a steric reconfiguration. Heparins contain a specific
      pentasaccharide unit which is the minimum requirement for AT binding. The
      glycosaminoglycan (GAG) heparan sulfate found on endothelial cell surfaces also
      contains this pentasaccharide and can thus "activate" AT. It is believed that
      much of the physiological inactivation of enzymes by AT occurs on the
      endothelium, mediated by heparan sulfate. The binding of AT to the GAGs also
      releases prostacyclin which possesses strong antiinflammatory properties.
      Deficiencies of AT are inherited or acquired. Only acquired defects due to
      increased consumption are discussed, most notably AT in DIC, especially DIC in
      sepsis. During acute DIC, clotting factors and inhibitors are consumed faster
      than they can be reproduced. This consumption of AT is of great significance in
      DIC and sepsis, and plasma AT levels predict outcome. AT levels drop early in
      sepsis and laboratory signs of DIC can already be found in patients with SIRS and
      early sepsis. The important role of AT in DIC and sepsis is the basis for
      considering antithrombin concentrates as an additional therapeutic modality.

PMID- 9515777
TI  - The anti-inflammatory properties of antithrombin III: new therapeutic
      implications.
AB  - Antithrombin III (AT III) supplementation has proven to be effective in the
      treatment of disseminated intravascular coagulation. Administration of AT III is
      also useful for prevention of organ failure in animals challenged with endotoxin
      or bacteria and it increases the survival rate of such animals. Since inhibition
      of coagulation abnormalities failed to prevent organ failure in animals given
      bacteria, AT III may exert a therapeutic effect independent of its anticoagulant
      effect. This therapeutic mechanism of AT III has been explored using an animal
      model of septicemia. AT III prevented pulmonary vascular injury by inhibiting
      leukocyte activation in rats given endotoxin. This effect is mediated by the
      promotion of endothelial release of prostacyclin which inhibits leukocyte
      activation. Interaction of AT III with heparin-like glycosaminoglycans (GAGs) on
      the endothelial cell surface appears to be important for this effect. Heparin
      inhibits these therapeutic effects of AT III by preventing AT III from
      interacting with the cell surface heparin-like GAGs. This activity of AT III may
      explain why AT III prevents organ failure as well as coagulation abnormalities in
      patients with sepsis. This antiinflammatory activity of AT III may be useful for
      the treatment of organ failure such as in ischemia/reperfusion-induced organ
      dysfunction, in which activated leukocytes play a critical role.

PMID- 9515778
TI  - Derangements of coagulation and fibrinolysis in critically ill patients with
      sepsis and septic shock.
AB  - In patients with sepsis and septic shock, both coagulation and fibrinolysis are
      activated frequently leading to the syndrome of diffuse intravascular coagulation
      (DIC). The different mechanisms leading to abnormalities in coagulation and
      fibrinolysis are discussed in detail. The coagulation and fibrinolytic system
      appear to be influenced by the septic process largely independently, leading to a
      procoagulant imbalance between these systems. Coagulation is initiated by
      mediator-induced expression of tissue factor and is associated with consumption
      of the natural coagulation inhibitors antithrombin III, protein C, and protein S.
      As a result, high plasma levels of thrombin-antithrombin complex (TAT) can be
      found. The effects on fibrinolysis are dominated by (highly) increased levels of
      plasminogen activator inhibitor type 1 (PAI-1), leading to inadequate
      fibrinolysis. Although levels of plasminogen activator antigen are increased, its
      activity is almost completely inhibited by PAI-1. The resulting effects
      predispose to a procoagulant state, with widespread fibrin deposition, which may
      be an important mechanism contributing to multiple organ failure. A thorough
      understanding of the pathophysiological mechanisms underlying the DIC-syndrome is
      a prerequisite for a rational approach and future therapy for this severe
      complication of sepsis.

PMID- 9515779
TI  - Disseminated intravascular coagulation in patients with multiple organ failure of
      non-septic origin.
AB  - Disseminated intravascular coagulation (DIC) and associated multi-organ failure
      are serious and often terminal events of a variety of non-septic conditions. For
      the most part, these conditions are a result of tissue factor (thromboplastin)
      release from damaged tissues creating situations that favor thrombin formation.
      Thrombin's role in this process is critical and serves to induce the
      coagulopathy, as well as many of the other aspects of inflammation that
      contribute to the associated morbidity and mortality. Clinical disorders giving
      rise to DIC fall into categories of trauma, obstetrical complications,
      malignancies and a variety of inflammatory conditions. Diagnostic patterns for
      these disorders are well established with an expected decrease in platelets and
      fibrinogen, as well as antithrombin III, in addition to elevated levels of
      thrombin-antithrombin III complex, prothrombin fragment 1 + 2, and D-dimer; all
      of which serve to identify the hypercoagulable state. Management of these
      coagulopathies requires attention to the bleeding diathesis and the ongoing
      thrombotic complication. Supportive therapy usually is required to provide
      hemostasis. However, control of the coagulopathy is of equal importance and
      requires not only early intervention, but also administration of sufficient
      antithrombotic agents to reduce thrombin's ability to consume coagulation
      factors, as well as to stimulate inflammatory processes. Heparin has been
      employed effectively in many of these situations, but suffers from its potential
      to induce hemorrhage. Antithrombin III concentrate, however, is devoid of this
      risk and provides a unique alternative that has had a limited, but effective
      record of benefits. Further proof of its efficacy in multi-organ failure
      disorders is awaited.

PMID- 9515780
TI  - Treatment options for clinically recognized disseminated intravascular
      coagulation.
AB  - Current concepts of etiology and pathophysiology resulting in disseminated
      intravascular coagulation (DIC) form the basis of treatment of this hemostatic
      disorder. Due to the heterogeneous triggering diseases and different kinds of
      DIC, clinical symptoms such as predominant bleeding, thromboembolic complications
      or organ failure, clinical experience together with the profile of laboratory
      test results and their development over time provide the basis for the
      individually tailored treatment strategy. The guiding principle of therapy is to
      identify and vigorously treat the underlying cause of DIC without delay.
      Treatment options to correct the hemostatic defect and to dampen the
      intravascular clotting/fibrinolytic process include transfusion of blood
      products, heparin, antithrombin III, and antifibrinolytic agents. The
      availability of new drugs such as activated protein C, tissue factor pathway
      inhibitor, hirudin, or synthetic serine protease inhibitors, and the upcoming
      trials investigating the role of these and older treatment options will help us
      to more clearly recommend therapy in DIC of different etiology.

PMID- 9515781
TI  - Antithrombin III in animal models of sepsis and organ failure.
AB  - Antithrombin III (AT III) is the physiological inhibitor of thrombin and other
      serine proteases of the clotting cascade. In the development of sepsis, septic
      shock and organ failure, the plasma levels of AT III decrease considerably,
      suggesting the concept of a substitution therapy with the inhibitor. A decrease
      of AT III plasma levels might also be associated with other pathological
      disorders like trauma, burns, pancreatitis or preclampsia. Activation of
      coagulation and consumption of AT III is the consequence of a generalized
      inflammation called SIRS (systemic inflammatory response syndrome). The clotting
      cascade is also frequently activated after organ transplantation, especially if
      organs are grafted between different species (xenotransplantation). During the
      past years AT III has been investigated in numerous corresponding disease models
      in different animal species which will be reviewed here. The bulk of evidence
      suggests, that AT III substitution reduces morbidity and mortality in the
      diseased animals. While gaining more experience with AT III, the concept of
      substitution therapy to maximal baseline plasma levels (100%) appears to become
      insufficient. Evidence from clinical and preclinical studies now suggests to
      adjust the AT III plasma levels to about 200%, i.e., doubling the normal value.
      During the last few years several authors proposed that AT III might not only be
      an anti-thrombotic agent, but to have in addition an anti-inflammatory effect.

PMID- 9515782
TI  - Clinical experience with antithrombin III concentrates in critically ill patients
      with sepsis and multiple organ failure.
AB  - Despite improvements in critical care medicine and the development and aggressive
      use of potent broad-spectrum anti-microbial agents, mortality due to severe
      sepsis has not changed during the recent years and still comes to 35% to 45%. For
      quite a long time our understanding of the pathophysiology of sepsis was mainly
      focused on endotoxin and proinflammatory cytokines like tumor necrosis factor or
      interleukin-1. Now it is generally accepted that many signs and symptoms of
      sepsis are not directly mediated by cytokines but are transmitted through other
      mediator systems. The coagulation system comes into play especially when the
      septic process progresses to malperfusion and organ failure. Antithrombin III is
      an important inhibitor of the intrinsic, extrinsic and common pathway of
      coagulation. Recently, evidence has been accumulating that there is an additional
      anti-inflammatory potential of the drug. Currently there are several clinical
      trials ongoing to investigate whether this effect is of clinical relevance in the
      treatment of patients with severe sepsis.

PMID- 9515783
TI  - Epilogue: disseminated intravascular coagulation and antithrombin III in
      intensive care medicine: pathophysiological insights and therapeutic hopes.

PMID- 9515784
TI  - Enhanced intestinal adenomatous polyp formation in Pms2-/-;Min mice.
AB  - Analysis of two human familial cancer syndromes, hereditary nonpolyposis
      colorectal cancer and familial adenomatous polyposis, indicates that mutations in
      either one of four DNA mismatch repair gene homologues or the adenomatous
      polyposis coli (APC) gene, respectively, are important for the development of
      colorectal cancer. To further investigate the role of DNA mismatch repair in
      intestinal tumorigenesis, we generated mice with mutations in both Apc and the
      DNA mismatch repair gene, Pms2. Whereas Pms2-deficient mice do not develop
      intestinal tumors, mice deficient in Pms2 and heterozygous for Min, an allele of
      Apc, develop approximately three times the number of small intestinal adenomas
      and four times the number of colon adenomas relative to Min and Pms2+/-;Min mice.
      Although Pms2 deficiency clearly increases adenoma formation in the Min
      background, histological analysis indicated no clear evidence for progression to
      carcinoma.

PMID- 9515785
TI  - Elevated and absent pRb expression is associated with bladder cancer progression
      and has cooperative effects with p53.
AB  - Rb protein (pRb) expression was evaluated in 185 cases of transitional cell
      carcinoma of the bladder from patients that underwent radical cystectomy. Tumors
      were stratified into three categories based on the percentage of nuclei
      expressing pRb: (a) 0, 0% of tumor cells showing nuclear reactivity; (b) 1+, 1
      50% of tumor cells showing nuclear reactivity; and (c) 2+, >50% of tumor cells
      showing nuclear reactivity. Cases with undetectable (pRb 0) and high (pRb 2+) pRb
      reactivity had identical rates of recurrence. These cases had significantly
      higher recurrence (P = 0.0001) and lower survival rates (P = 0.0002) compared to
      cases with moderate (pRb 1+) pRb reactivity, indicating that high levels of pRb
      expression may reflect a dysfunctional (altered) Rb pathway. The tumors were also
      examined for alterations in p53 expression; patients with tumors altered in both
      p53 and pRb had significantly increased rates of recurrence (P < 0.0001) and
      survival (P < 0.0001) compared to patients with no alterations in either p53 or
      pRb; patients with alterations in only one of these proteins had intermediate
      rates of recurrence and survival. These results suggest that: (a) bladder cancers
      with high pRb expression do not show the tumor suppressor effects of the protein;
      and (b) alteration in both p53 and pRb may act in cooperative or synergistic ways
      to promote tumor progression.

PMID- 9515786
TI  - T-loop deletion of CDC2 from breast cancer tissues eliminates binding to cyclin
      B1 and cyclin-dependent kinase inhibitor p21.
AB  - The eukaryotic cell cycle is regulated by a highly conserved family of protein
      kinases, the cyclin-dependent kinases (CDKs). Monomeric free CDKs do not possess
      enzymatic activity, largely due to the steric hindrance caused by the T-loop at
      the entrance of the catalytic cleft, making ATP inaccessible to the substrate.
      Binding of a cyclin, primarily to the NH2-terminal lobe of the CDK that surrounds
      the PSTAIRE helix, induces a large conformational change in the PSTAIRE helix of
      the CDK and also causes the T-loop to move out of the way of the catalytic cleft.
      We identified from breast cancer tissues a novel variant of human CDC2, termed
      CDC2deltaT, that lacks 171 nucleotides corresponding to 57 amino acids, which
      compose most of the T-loop. CDC2deltaT was detected in 10 of 14 breast cancer
      tissues analyzed, whereas it was not detectable in diploid human fibroblast cell
      lines or in interleukin 2-stimulated normal human lymphocytes. CDC2deltaT protein
      is unable to complex with cyclin B1 and lacks histone H1 kinase activity.
      CDC2deltaT also fails to bind to the CDK inhibitor p21. These results indicate
      that the T-loop not only plays a key role in keeping a free CDK in its inactive
      state but also in facilitating CDK activation by promoting cyclin binding.

PMID- 9515787
TI  - Heparan/chondroitin/dermatan sulfate primer 2-(6-hydroxynaphthyl)-O-beta-D
      xylopyranoside preferentially inhibits growth of transformed cells.
AB  - Xylose forms the direct carbohydrate-protein link in extra- or pericellular
      proteoglycans (PGs) that are substituted with either chondroitin sulfate
      (CS)/dermatan sulfate (DS) and/or heparan sulfate (HS). Cell surface PGs carrying
      HS are important regulators of cell growth. Xylose coupled to an aromatic
      compound can enter cells and initiate either CS/DS synthesis or both HS and CS/DS
      synthesis, depending on the nature of the aromatic adduct. Here, we show that 2
      (6-hydroxynaphthyl)-O-beta-D-xylopyranoside, which can prime both types of glycan
      chains, inhibits growth of a set of normal and transformed cells. Transformed
      cells are preferentially inhibited, and at a concentration of 0.15-0.20 mM
      xyloside, transformed cells are totally growth arrested, whereas normal cells are
      only < or = 50% inhibited. No inhibition of growth is observed with the
      stereoisomeric 2-(6-hydroxynaphthyl)-O-beta-L-xylopyranoside, which does not
      prime glycosaminoglycan synthesis at all; with the nonhydroxylated 2-naphthyl-O
      beta-D-xylopyranoside, which only primes CS/DS synthesis under these conditions;
      or with p-nitrophenyl-O-beta-D-xylopyranoside, which is known to prime only CS/DS
      synthesis. We conclude that growth inhibition is due to priming of HS and/or
      CS/DS synthesis, which may either lead to the formation of specific
      antiproliferative glycans or glycan fragments or to interference with endogenous
      PG synthesis and turnover.

PMID- 9515788
TI  - Frequent p53 mutations at dipyrimidine sites in patients with pyothorax
      associated lymphoma.
AB  - A high incidence of non-Hodgkin's lymphoma of the pleural cavity has developed in
      Japanese patients with long-standing pyothorax (38 years on average) resulting
      from artificial pneumothorax for the treatment of pulmonary tuberculosis or
      tuberculous pleuritis. Patients with pyothorax-associated lymphoma (PAL) have
      long been exposed to antituberculous drugs, antibiotics, bacterial or viral
      products, and frequent diagnostic radiation for the confirmation of pneumothorax
      and pyothorax. We analyzed p53 mutations on paraffin-embedded specimens from 21
      patients with PAL by PCR-single-strand conformational polymorphism followed by
      direct sequencing. An unusually high frequency of p53 mutations (14 of 21 cases,
      67%) was detected in the PAL specimens, and mutations consisted of 13 nucleotide
      substitutions and 1 deletion. Furthermore, 10 of 13 substitutions (77%) occurred
      at dipyrimidine sites (CC:GG to CT:GA substitution). Such specificity has not
      been reported, except for solar light-related skin cancer and AIDS-related
      lymphoma in some parts. An UV light mimetic agent may be produced in the long
      history of chronic inflammation in tuberculosis or immunodeficient patients.

PMID- 9515789
TI  - Expression of CD44 variant exon 6 in stage I non-small cell lung carcinoma as a
      prognostic factor.
AB  - Specific CD44 isoforms are the surface adhesion molecules that have been shown to
      be associated with metastasis. In the present study, the role of the expression
      of standard and variant CD44 isoform (CD44s and CD44v6) as prognostic indicators
      in pathological stage I non-small cell lung carcinoma was investigated
      immunohistologically using monoclonal antibodies. The results showed that the
      expression of CD44v6 correlates with adverse prognosis in stage I non-small cell
      lung carcinoma but not CD44s. The 5-year survival rate of the patients with
      CD44v6-positive tumors was 50%, which was significantly lower than that of CD44v6
      negative patients (88%; P = 0.001). The incidence of recurrent distant metastasis
      in the CD44v6-positive patients (45%; 9 of 20 patients) was significantly higher
      than that in the CD44v6-negative patients (20%; 10 of 49 patients; P = 0.038),
      suggesting the involvement of CD44v6 in hematogeneous metastasis of lung
      carcinoma. Although the incidence of the expression of CD44v6 in squamous cell
      carcinoma was significantly higher than that in adenocarcinoma, histological type
      was not a significant prognostic factor. No significant correlation was found
      between the expression of CD44v6 and lymphatic or vascular vessel invasion,
      although lymphatic vessel invasion was found to be an independent prognostic
      factor in the multivariate analysis. To investigate the relationship between the
      expression of CD44v6 and proliferative activity of tumor cells, the expression of
      proliferating cell nuclear antigen (PCNA) was examined. The expression of CD44v6
      was more frequently observed in PCNA-positive patients than in PCNA-negative
      patients (P = 0.019), but the expression of PCNA was not a statistically
      significant prognostic indicator. The results of multivariate analysis by the Cox
      proportional hazards model showed that CD44v6 was an independent prognostic
      indicator. We concluded that the expression of CD44v6 is a useful prognostic
      factor in stage I non-small cell lung carcinoma.

PMID- 9515790
TI  - Eleutherobin, a novel cytotoxic agent that induces tubulin polymerization, is
      similar to paclitaxel (Taxol).
AB  - Eleutherobin is a novel natural product isolated from a marine soft coral that is
      extremely potent for inducing tubulin polymerization in vitro and is cytotoxic
      for cancer cells with an IC50 similar to that of paclitaxel. This compound is
      cross-resistant along with other multidrug-resistant agents against P
      glycoprotein-expressing cells and is cross-resistant with paclitaxel against a
      cell line that has altered tubulin. In mechanistic studies, eleutherobin shares
      with paclitaxel the ability to induce tubulin polymerization in vitro and is most
      likely cytotoxic by virtue of this mechanism. Human colon carcinoma cells exposed
      to eleutherobin contain multiple micronuclei and microtubule bundles, and they
      arrest in mitosis, depending on concentration, cell line, and length of exposure.
      These morphological abnormalities appearing in cultured cells are
      indistinguishable from those induced by paclitaxel. Electron microscopy reveals
      that eleutherobin induces homogeneous populations of long, rigid microtubules
      similar to those formed by paclitaxel. Thus, eleutherobin is a new chemotype with
      a mechanism of action similar to that of paclitaxel and, as such, has promising
      potential as a new anticancer agent.

PMID- 9515791
TI  - An anti-CD30 chimeric receptor that mediates CD3-zeta-independent T-cell
      activation against Hodgkin's lymphoma cells in the presence of soluble CD30.
AB  - Hodgkin's lymphoma patients fail to establish an efficient cellular response
      against CD30+ Hodgkin/Reed-Sternberg cells. An impaired T-cell receptor/CD3-zeta
      mediated activation of T cells is thought to be involved in this situation. We
      here present a chimeric anti-CD30 receptor that mediates MHC and T-cell
      receptor/CD3-zeta-independent T-cell activation against CD30+ lymphoma cells even
      in the presence of soluble CD30. The receptor consists of the binding domain of
      the monoclonal antibody HRS3 and the signaling unit of the Fc epsilonRI-receptor
      gamma-chain. After expression in MD45 T cells, receptor cross-linking with
      immobilized anti-idiotypic monoclonal antibody and CD30+ cells, respectively,
      results in increased interleukin 2 secretion and specific cytolysis of CD30+
      Hodgkin's lymphoma cells. Soluble CD30 in concentrations up to 6000 units/ml did
      not interfere with cellular activation induced by membrane-bound antigen. This
      demonstrates the feasibility of the chimeric anti-CD30-scFv-gamma receptor in
      CD30+ lymphoma cell targeting, even in the presence of as high concentrations of
      soluble CD30 as are found in patients during progression of the disease.

PMID- 9515792
TI  - BRCA1 up-regulation is associated with repair-mediated resistance to cis
      diamminedichloroplatinum(II).
AB  - We sought to identify novel genes associated with cis
      diamminedichloroplatinum(II) (CDDP) resistance, and by differential display
      analysis, we found that the human breast and ovarian cancer susceptibility gene
      BRCA1 was overexpressed in CDDP-resistant MCF-7 cells. A recent report that BRCA1
      and human Rad51 colocalize in S-phase cells suggests a role for BRCA1 in DNA
      damage repair. We hypothesized that BRCA1 plays a role in DNA damage repair
      mediated CDDP resistance. In CCDP-resistant variants of breast and ovarian
      carcinoma cell lines, MCF-7 CDDP/R and SKOV-3 CDDP/R, we found increased levels
      of BRCA1 protein, and we determined that the SKOV-3 CDDP/R cell line is
      significantly more proficient at DNA damage repair. Antisense inhibition of BRCA1
      in this cell line resulted in an increased sensitivity to CDDP, a decreased
      proficiency of DNA repair, and an enhanced rate of apoptosis. These data support
      the hypothesis that BRCA1 is a gene involved in DNA damage repair.

PMID- 9515793
TI  - Mutations of the DPC4/Smad4 gene in biliary tract carcinoma.
AB  - A candidate tumor suppressor gene, DPC4, located at 18q21.1, has recently been
      shown to be inactivated in half of pancreatic adenocarcinomas. The close
      developmental relationship of the pancreas and biliary tract prompted us to
      determine the role of DPC4 in the multistep carcinogenesis of biliary tract
      carcinoma. A search for mutations in the genomic sequence of the highly conserved
      COOH-terminal domain of DPC4 (exons 8-11) was performed by single-strand
      conformational polymorphism analysis. Five of 32 (16%) primary biliary tract
      carcinomas had point mutations in the DPC4 sequence. Interestingly, inactivation
      of DPC4 was especially common in carcinomas originating from the common bile duct
      (four of eight specimens analyzed), suggesting an important role for DPC4 in the
      development of this subtype of biliary tract tumor.

PMID- 9515794
TI  - High frequency of beta-catenin (ctnnb1) mutations in the colon tumors induced by
      two heterocyclic amines in the F344 rat.
AB  - Activating mutations in the beta-catenin (CTNNB1) gene corresponding to N
      terminal phosphorylation sites in the protein have been implicated in the
      development of human colon cancer. To determine the possible involvement of such
      mutations during chemically induced colon carcinogenesis, we examined the
      corresponding region of Ctnnb1 in colon tumors induced in the F344 rat by two
      cooked meat heterocyclic amines, 2-amino-3-methylimidazo[4,5-f]quinoline and 2
      amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). All of the colon tumors
      induced by 2-amino-3-methylimidazo[4,5-f]quinoline that were examined (5 of 5)
      and 4 of 7 PhIP-induced colon tumors had mutations within or flanking codons
      corresponding to important phosphorylation sites in beta-catenin. None of the
      colon tumors bearing Ctnnb1 mutations had genetic changes in the Apc gene, and
      those that contained wild-type Ctnnb1 were known from our previous work to
      contain Apc mutations. The results provide evidence for a major role of the beta
      catenin/Apc pathway in the development of heterocyclic amine-induced colon tumors
      and give further weight to the view that regulation of beta-catenin is critical
      to the tumor suppressive effects of Apc during colon carcinogenesis. In contrast,
      Ctnnb1 mutations were completely absent in 23 PhIP-induced mammary tumors, in
      accordance with recent work showing that human breast carcinomas lack mutations
      in CTNNB1.

PMID- 9515795
TI  - Mutational analysis of the APC/beta-catenin/Tcf pathway in colorectal cancer.
AB  - Mutation of the adenomatous polyposis coli (APC) tumor suppressor gene initiates
      the majority of colorectal (CR) cancers. One consequence of this inactivation is
      constitutive activation of beta-catenin/Tcf-mediated transcription. To further
      explore the role of the APC/beta-catenin/Tcf pathway in CR tumorigenesis, we
      searched for mutations in genes implicated in this pathway in CR tumors lacking
      APC mutations. No mutations of the gamma-catenin (CTNNG1), GSK-3alpha (GSK3A), or
      GSK-3beta (GSK3B) genes were detected. In contrast, mutations in the NH2-terminal
      regulatory domain of beta-catenin (CTNNB1) were found in 13 of 27 (48%) CR tumors
      lacking APC mutations. Mutations in the beta-catenin regulatory domain and APC
      were observed to be mutually exclusive, consistent with their equivalent effects
      on beta-catenin stability and Tcf transactivation. In addition, we found that
      CTNNB1 mutations can occur in the early, adenomatous stage of CR neoplasia, as
      has been observed previously with APC mutations. These results suggest that
      CTNNB1 mutations can uniquely substitute for APC mutations in CR tumors and that
      beta-catenin signaling plays a critical role in CR tumorigenesis.

PMID- 9515796
TI  - Inhibition of the p38 mitogen-activated protein kinase by SB 203580 blocks PMA
      induced Mr 92,000 type IV collagenase secretion and in vitro invasion.
AB  - Although the p38 mitogen-activated protein kinase (MAPK) has been implicated in
      signal transduction events, its role in regulating the Mr 92,000 type IV
      collagenase matrix metalloprotease-9 (MMP-9) and in vitro invasiveness in cancer
      has not yet been determined. We made the surprising observation that, in a human
      squamous cell carcinoma cell line (UM-SCC-1), phorbol ester-enhanced MMP-9
      secretion and in vitro invasiveness were associated with a strong activation of
      the p38 MAPK and its downstream target, MAPK-activated protein kinase-2. To
      determine the role of p38 activation in these events, we investigated the effect
      of SB 203580, a novel specific p38 inhibitor, on protease expression and in vitro
      invasion of these cells. We found that inhibition of p38 by SB 203580 resulted in
      the almost complete reduction of phorbol myristate acetate-induced MMP-9
      secretion but not of urokinase-type plasminogen activator secretion. In contrast,
      the activation of a transiently transfected wild-type MMP-9 promoter by MEKK-1, a
      specific c-Jun NH2-terminal kinase activator, was only marginally inhibited by
      the compound, arguing for the specificity of SB 203580. Moreover, phorbol
      myristate acetate-enhanced in vitro invasion was completely blocked by SB 203580,
      whereas p38 inhibition had little effect on growth. These findings suggest that
      activation of p38 may contribute to a more invasive phenotype in vitro, possibly
      via the expression of MMP-9, and that targeting of p38 using SB 203580 may
      provide a novel means of controlling invasion of cancers in which this MAPK is
      activated.

PMID- 9515797
TI  - A distinct region of chromosome 19p13.3 associated with the sporadic form of
      adenoma malignum of the uterine cervix.
AB  - Adenoma malignum (AM) is known to be one of the malignant tumors that is commonly
      associated with Peutz-Jeghers syndrome. Recently, the genetic locus of Peutz
      Jeghers syndrome was mapped to the telomeric region of chromosome 19p. We
      analyzed nine sporadic cases of AM with high-density loss of heterozygosity to
      study the region of chromosome 19p13.2-13.3 using eight microsatellite markers.
      Our deletion mapping data revealed a distinct region with 100% loss of
      heterozygosity frequency at marker D19S216. This result indicates that a putative
      tumor suppressor gene for AM is located at D19S216 on chromosomal band 19p13.3
      and plays an important role in AM tumorigenesis.

PMID- 9515798
TI  - Participation of iron and nitric oxide in the mutagenicity of asbestos in hgprt-,
      gpt+ Chinese hamster V79 cells.
AB  - Crocidolite asbestos is known to cause cellular damage, leading to asbestosis,
      bronchogenic carcinoma, and mesothelioma in humans. The mechanism responsible for
      the carcinogenicity of asbestos is not known. Iron associated with asbestos is
      thought to play a role by catalyzing the formation of reactive oxygen species,
      which may cause DNA damage, leading to mutations and cancer. Here, we examined
      whether asbestos can induce mutations in Chinese hamster hgprt+ V79 cells or
      transgenic hgprt-, gpt+ V79 cells (G12). Treatment with 6 microg/cm2 crocidolite
      for 24 h caused a 2-fold increase in the mutation frequency at the gpt locus of
      G12 cells, but no increase at the hgprt locus of V79 cells. The mutation
      frequency at the gpt locus of G12 cells increased with increasing treatment dose
      of crocidolite. The mutations induced by crocidolite appeared to be due to the
      generation of reactive oxygen species catalyzed by iron associated with the
      fibers, because treatment of G12 cells in iron-free medium with fibers from which
      redox active iron had been removed with desferrioxamine B prevented all of the
      gpt- mutations above untreated control levels. In addition, treatment of cells
      with a soluble form of iron, 1.5 mM ferric ammonium citrate, resulted in an
      increase in mutation frequency at the gpt locus of approximately 1.5 fold above
      that of untreated G12 cells with no increase in mutations at the hgprt locus of
      V79 cells with ferric ammonium citrate. We also investigated the effect of nitric
      oxide on the mutagenicity of crocidolite in G12 cells. When G12 cells were
      treated with 3 microg/cm2 of crocidolite in the presence of nitric oxide
      generating compound, 200 microM diethyltriamine/NO, the mutation frequency
      increased to a level that was more than additive for crocidolite or
      diethyltriamine/NO treatment alone. These results strongly suggest that the
      presence of iron and nitric oxide may either lead to the generation of another
      reactive, mutagenic species, such as peroxynitrite, or that nitric oxide inhibits
      a DNA repair enzyme(s), leading to an increase in mutations.

PMID- 9515799
TI  - Ki-ras mutation and p53 overexpression predict the clinical behavior of
      colorectal cancer: a Southwest Oncology Group study.
AB  - We assessed Ki-ras mutations by single-strand conformation polymorphism followed
      by DNA sequencing, p53 expression by immunohistochemistry, ploidy status, and S
      phase fraction in 66 stage II and 163 stage III colon cancer patients enrolled on
      a randomized trial of surgery followed by observation or adjuvant levamisole or 5
      fluorouracil (5FU) plus levamisole (Intergroup Trial 0035) to see whether these
      factors were independently associated with survival or with differential effects
      of adjuvant therapy. A Cox proportional hazards survival model was used to
      describe marker effects and therapy by marker interactions, with adjustment for
      the clinical covariates affecting survival. A Bonferroni adjustment was used to
      account for multiple testing. Mutation of the Ki-ras gene was found in 41% of the
      cancers and was associated with a poor prognosis in stage II but not stage III.
      In stage II, 7-year survival was 86% versus 58% in those with wild type versus Ki
      ras mutations. After adjustment for treatment and clinical variables, the hazard
      ratio (HR) for death was 4.5; 95% confidence interval (CI), 1.7-12.1 (P = 0.012).
      p53 overexpression was found in 63% of cancers and was associated with a
      favorable survival in stage III but not stage II. Seven-year survival in stage
      III was 56% with p53 overexpression versus 43% with no p53 expression (HR, 2.2;
      95% CI, 1.3-3.6; P = 0.012). Aneuploidy was more common in stage III than in
      stage II (66 versus 47%; P = 0.009) but was not independently related to survival
      in either group. The proliferative rate was greater in aneuploid than in diploid
      cancers but was not related to survival. There was no benefit of adjuvant therapy
      in stage II nor in any of the stage II subgroups defined by mutational status. In
      stage III, adjuvant therapy with 5FU plus levamisole improved 7-year survival in
      patients with wild-type Ki-ras (76 versus 44%; HR, 0.4; 95% CI, 0.2-0.8) and in
      those without p53 overexpression (64 versus 26%; HR, 0.3; 95% CI, 0.1-0.7).
      Adjuvant therapy did not benefit those with Ki-ras mutations or p53
      overexpression. The effects of adjuvant therapy did not differ according to
      ploidy status or proliferative rate. Ki-ras mutation is a significant risk factor
      for death in stage II, and the absence of p53 expression is a significant risk
      factor for death in stage III colon cancer after adjustment for treatment and
      clinical covariates. Exploratory analyses suggest that patients with stage III
      colon cancer with wild-type Ki-ras or no p53 expression benefit from adjuvant 5FU
      plus levamisole, whereas those with Ki-ras mutations or p53 overexpression do
      not. An independent study will be required to determine whether response to
      adjuvant therapy in colon cancer depends on mutational status.

PMID- 9515800
TI  - Elevated insulin-like growth factor I receptor autophosphorylation and kinase
      activity in human breast cancer.
AB  - Insulin-like growth factor I action has been implicated in the pathogenesis of
      many different malignancies, including breast cancer. Insulin-like growth factor
      I receptors (IGF-IRs) are overexpressed in virtually all breast cancer cell
      lines, in which they are believed to enhance growth and inhibit apoptosis. In
      this study, the functional activity of IGF-IRs from normal and malignant human
      breast tissue was assessed. IGF-IR expression was 14-fold higher in malignant
      breast tissue than in normal breast tissue. IGF-IR autophosphorylation and kinase
      activity were 2-4-fold higher in purified receptor preparations from malignant
      breast tissue as compared to normal breast tissue when normalized for receptor
      number. This increase in receptor function, coupled with the enhanced receptor
      expression, amounts to a 40-fold elevation in IGF-IR tyrosine kinase activity in
      malignant breast tissue. The enhanced receptor autophosphorylation and kinase
      activity were observed in the absence of hormonal stimulation and seem to result
      from an alteration in the intrinsic activity of the receptor itself. Protein
      tyrosine phosphatase activity is also increased in malignant breast tissue. These
      data suggest that the IGF-IR is an important target for breast cancer therapy.

PMID- 9515801
TI  - The antiproliferative activity of DMDC is modulated by inhibition of cytidine
      deaminase.
AB  - We showed that the efficacy of the new 2'-deoxycytidine (2'-dCyd) analogue
      antimetabolite 2'-deoxy-2'-methylidenecytidine (DMDC) correlates well with tumor
      levels of cytidine (Cyd) deaminase in human cancer xenograft models. DMDC was
      highly effective in tumors with higher levels of Cyd deaminase, whereas lower
      levels yielded only slight activity. In contrast, gemcitabine (2',2'
      difluorodeoxycytidine), which has action mechanisms similar to those of DMDC, is
      only slightly active in tumors with higher levels of the enzyme. In the present
      study, we investigated the roles of Cyd deaminase in the antitumor activity of
      the two 2'-dCyd antimetabolites in 13 human cancer cell lines. Tetrahydrouridine,
      an inhibitor of Cyd deaminase, reduced the antiproliferative activity of DMDC (P
      = 0.0015). Furthermore, tumor cells transfected with the gene of human Cyd
      deaminase become more susceptible to DMDC both in vitro and in vivo. These
      results indicate that Cyd deaminase is indeed essential for the activity of DMDC.
      In contrast, the antiproliferative activity of gemcitabine was increased to some
      extent by tetrahydrouridine (P = 0.0277), particularly in tumor cell lines with
      higher levels of Cyd deaminase. This suggests that higher levels of Cyd deaminase
      may inactivate gemcitabine. Among nucleosides and deoxynucleosides tested, only
      dCyd, a natural substrate of both Cyd deaminase and dCyd kinase, suppressed the
      antiproliferative activity of DMDC by up to 150-fold. Because the Vmax/Km of DMDC
      for dCyd kinase was 8-fold lower than that for dCyd, the activation of DMDC to
      DMDC monophosphate (DMDCMP) by dCyd kinase might be competitively inhibited by
      dCyd. In addition, the dCyd concentrations in human cancer xenografts were
      inversely correlated with levels of Cyd deaminase activity. It is therefore
      suggested that higher levels of Cyd deaminase reduce the intrinsic cellular
      concentrations of dCyd in tumors, resulting in efficient activation of DMDC to
      DMDCMP by dCyd kinase. These results indicate that the efficacy of DMDC may be
      predicted by measuring the activity of Cyd deaminase in tumor tissues before
      treatment starts and that DMDC may be exploited in a new treatment modality:
      tumor enzyme-driven cancer chemotherapy.

PMID- 9515802
TI  - Intracellular expression of an antibody fragment-neutralizing p21 ras promotes
      tumor regression.
AB  - Mutated ras genes are found in a large number of human tumors and, therefore,
      constitute one of the primary targets for cancer treatment. Microinjection of the
      neutralizing anti-Ras monoclonal antibody Y13-259 was previously reported to
      induce transient phenotypic reversion of ras-transformed rodent fibroblasts in
      vitro. We have prepared a single-chain Fv fragment (scFv) derived from Y13-259,
      and here, we show that intracellular expression of the scFv led to the specific
      inhibition of the Ras signaling pathway in Xenopus laevis oocytes and NIH3T3
      fibroblasts. Moreover, neutralizing Ras with the scFv specifically promoted
      apoptosis in vitro in human cancer cells but not in untransformed cells. As a
      step toward cancer gene therapy, we finally demonstrated that intratumor
      transduction of HCT116 colon carcinoma cells with the anti-Ras scFv using an
      adenoviral vector elicited sustained tumor regression in nude mice.

PMID- 9515803
TI  - Low potency of taxol at microtubule minus ends: implications for its antimitotic
      and therapeutic mechanism.
AB  - In many cells, low concentrations of Taxol potently block mitosis at the
      transition from metaphase to anaphase, with no change in microtubule polymer mass
      and no microtubule bundling. Mitotic block ultimately results in apoptotic cell
      death and appears to be the most potent antitumor mechanism of Taxol (M. A.
      Jordan et al., Cancer Res. 56: 816-825, 1996). Mitotic inhibition results, at
      least in part, from stabilization of growing and shortening dynamics,
      specifically at the plus ends of microtubules, by the binding of very few Taxol
      molecules to the microtubule surface (M. A. Jordan et al., Proc. Natl. Acad. Sci.
      USA, 90: 9552-9556, 1993; W. B. Derry et al., Biochemistry, 34: 2203-2211, 1995).
      A number of actions of Taxol on mitotic spindle function may be due to its
      effects on microtubule dynamics at the minus ends of microtubules, effects that
      previously have not been described. Here, we determined the effects of Taxol on
      minus ends of purified microtubules at steady state. In contrast to the strong
      stabilizing effects on plus ends, substoichiometric ratios of Taxol bound to
      tubulin in microtubules did not affect growing, shortening, or dynamicity at
      minus ends. Thus, in blocked mitotic cells, Taxol can potently suppress dynamics
      at plus ends of spindle microtubules, whereas its impotence at minus ends permits
      continued microtubule depolymerization at the spindle poles. Differential effects
      of Taxol at opposite microtubule ends may explain Taxol's actions on spindle
      structure and function and its unique potent antitumor action.

PMID- 9515804
TI  - Carbogen breathing increases 5-fluorouracil uptake and cytotoxicity in hypoxic
      murine RIF-1 tumors: a magnetic resonance study in vivo.
AB  - The purpose of this study was to examine the effect of carbogen gas (95% O2-5%
      CO2) on uptake and metabolism of 5-fluorouracil (5FU) in murine RIF-1 tumors and
      their growth in vivo. In addition, we have explored the mechanisms by which
      carbogen can transiently affect the physiology of RIF-1 tumors. After i.p.
      injection of 1 mmol/kg 5FU into C3H mice, the uptake and metabolism of the drug
      by s.c. RIF-1 tumors was followed for 2 h noninvasively using 19F-magnetic
      resonance spectroscopy (MRS). In all animals, irrespective of tumor size,
      carbogen caused a significant increase in the half-life (t(1/2)) of the
      elimination of 5FU by the tumor and a significant increase in growth inhibition.
      In 2-3-g tumors (group II), carbogen also caused increased 5FU uptake and
      metabolism to the cytotoxic 5-fluoronucleotides, whereas in 0.8-1.5-g tumors
      (group I), only the t(1/2) was slightly increased. These results suggested that
      tumor size was an important factor in the effect of carbogen on tumor physiology.
      Measurements of RIF-1 tumor vascular and necrotic volume showed no significant
      differences between group I and group II tumors. However, 1H-MR images of RIF-1
      tumors showed that carbogen caused a transient decrease in signal intensity,
      which correlated positively (P = 0.02) with tumor size, suggesting that larger
      tumors responded to carbogen by transiently increasing O2 uptake from the blood.
      19F-MRS was used to measure RIF-1 tumor retention of the fluorinated
      nitroimidazole SR-4554. These studies also showed a positive correlation (P =
      0.001) with tumor size, implying greater hypoxia in larger tumors. We propose
      that carbogen may transiently open nonfunctional blood vessels in the tumor,
      allowing increased leakage of 5FU from the plasma into the extracellular space.
      5FU transport is known to be pH dependent. Intra- and extracellular tumor pH was
      measured using 31P- and 19F-MRS, which showed that carbogen caused a significant
      decrease in the extracellular pH of 0.1 unit in group II tumors and a consequent
      increase in the negative pH gradient across the tumor plasma membrane, which can
      cause increased 5FU uptake. The pH gradient was unaffected in group I tumors. We
      conclude that carbogen breathing can increase tumor uptake of 5FU by two
      independent mechanisms involving changes in tumor blood flow and pH, which
      consequently cause increased formation of 5-fluoronucleotides and cytotoxicity.
      The effect seems more pronounced in hypoxic tumors, implying that carbogen would
      be a valuable aid in clinical chemotherapy.

PMID- 9515805
TI  - Elucidation of the mechanism enabling tumor selective prodrug monotherapy.
AB  - Elucidation of the mechanism enabling tumor selective PMT in vivo with
      appropriate glucuronyl-spacer-doxorubicin prodrugs, such as HMR 1826, is
      important for the design of clinical studies, as well as for the development of
      more selective drugs. Enzyme histochemistry, immunohistochemistry, and the
      terminal deoxytransferase technique were applied using human cryopreserved cancer
      tissues, normal human, monkey, and mouse tissues, and human tumor xenografts to
      examine mechanisms underlying the selectivity of successful PMT with HMR 1826. It
      could unambiguously be shown by enzyme histochemistry that necrotic areas in
      human cancers are the sites in which lysosomal beta-glucuronidase is liberated
      extracellularly in high local concentrations. The cells responsible for the
      liberation of the enzyme are mainly acute and chronic inflammatory cells, as
      shown by IHC. Furthermore, it could be demonstrated that beta-glucuronidase
      liberated in necrotic areas of tumors can activate HMR 1826, resulting in
      increased doxorubicin deposition in human tumor xenografts or in human lung
      cancers subjected to extracorporal perfusion, compared to chemotherapy with
      doxorubicin. Additionally, the doxorubicin load to normal tissues was
      significantly reduced compared to chemotherapy with doxorubicin. Surprisingly,
      the increased doxorubicin deposition in tumors also resulted in strong antitumor
      effects also in cancers resistant to maximum tolerated doses of systemic
      doxorubicin. Finally, toxicity studies in mice and monkeys revealed an excellent
      tolerability of HMR 1826, up to a dose of 3 g/m2 (monkeys). These data suggest
      that HMR 1826 is a promising candidate for clinical development.

PMID- 9515806
TI  - Treatment of hepatic metastasis of the colon26 adenocarcinoma with an alpha
      galactosylceramide, KRN7000.
AB  - Colorectal liver metastasis is clinically a major problem. We examined the
      antitumor activity of KRN7000, an alpha-galactosylceramide, on mice with liver
      metastases of adenocarcinoma Colon26 cells. KRN7000 treatment, beginning 1 day
      after tumor inoculation (day 1), significantly inhibited tumor growth in the
      liver, and its potency was equal to that of interleukin 12. KRN7000 treatment
      from day 3 caused regression of established Colon26 nodules. KRN7000
      administration resulted in a high percentage of cured mice that acquired tumor
      specific immunity. In addition, it appeared that highly activated, liver
      associated natural killer cells made the major contribution to the killing of
      Colon26 cells in the liver. These results suggest that KRN7000 may be useful for
      the treatment of colorectal liver metastasis.

PMID- 9515807
TI  - Non-small cell lung cancer cyclooxygenase-2-dependent regulation of cytokine
      balance in lymphocytes and macrophages: up-regulation of interleukin 10 and down
      regulation of interleukin 12 production.
AB  - Tumor-derived prostaglandin E2 (PGE2) modifies cytokine balance and inhibits host
      immunity. We hypothesized that a high level of PGE2 production by lung tumor
      cells is dependent on tumor cyclooxygenase (COX)-2 expression. We found that PGE2
      production by A549 non-small cell lung cancer (NSCLC) cells was elevated up to 50
      fold in response to interleukin (IL)-1beta. Reversal of IL-1beta-induced PGE2
      production in A549 cells was achieved by specific pharmacological or antisense
      oligonucleotide inhibition of COX-2 activity or expression. In contrast, specific
      COX-1 inhibition was not effective. Consistent with these findings, IL-1beta
      induced COX-2 mRNA expression and protein production in A549 cells. Specific
      inhibition of COX-2 abrogated the capacity of IL-1beta-stimulated A549 cells to
      induce IL-10 in lymphocytes and macrophages. Furthermore, specific inhibition of
      A549 COX-2 reversed the tumor-derived PGE2-dependent inhibition of macrophage IL
      12 production when whole blood was cultured in tumor supernatants. Our results
      indicate that lung tumor-derived PGE2 plays a pivotal role in promoting
      lymphocyte and macrophage IL-10 induction while simultaneously inhibiting
      macrophage IL-12 production. Immunohistochemistry of human NSCLC tissues obtained
      from lung cancer resection specimens revealed cytoplasmic staining for COX-2
      within tumor cells. This is the first description of functional COX-2 expression
      by NSCLC cells and the definition of a pathway whereby tumor COX-2 expression and
      a high level of PGE2 production mediate profound alteration in cytokine balance
      in the lung cancer microenvironment.

PMID- 9515808
TI  - Molecular mimicry of carcinoembryonic antigen by peptides derived from the
      structure of an anti-idiotype antibody.
AB  - Our goal was to use carcinoembryonic antigen (CEA) as a target for immunotherapy
      in CEA-positive cancer patients who are all immune tolerant to the native
      antigen. We isolated and characterized an anti-idiotype monoclonal antibody 3H1,
      which mimics a distinct and specific epitope of the Mr 180,000 CEA and can be
      used as a surrogate for CEA. In Phase Ib clinical trials in a group of 23
      advanced colorectal cancer patients, 3H1 induced both humoral and cellular anti
      3H1 responses, as well as anti-CEA immunity. To study the cellular immunity
      invoked by 3H1 at the molecular level, we have cloned and sequenced the cDNAs
      encoding the variable heavy and light chains of 3H1 and deduced the amino acid
      sequences of the encoded proteins. To identify any cross-reactive peptides of 3H1
      and CEA, we compared the amino acid sequences of 3H1 with those of CEA and found
      several regions of homology in 3H1 heavy and light chain variable domains, as
      well as in the framework regions. To search for potential cross-reactive T-cell
      epitopes, a number of peptides were synthesized based on 3H1/CEA homology and
      were used as stimulants in cell proliferation assays, using peripheral blood
      mononuclear cells from a group of 3H1-immunized CEA-positive cancer patients in
      the adjuvant setting. Two partially homologous peptides, designated LCD-2 (from
      3H1) and CEA-B (from CEA), were identified in 10 of 21 adjuvant patients by
      strong proliferation responses (stimulation index, 3-50-fold), which were
      extensively studied in five of these individuals over an extended period of time
      (12-24 months). We saw no correlation with the MHC class I haplotype of the
      patients. Analysis of the subtype of the responding T cells demonstrated that
      primarily CD4+ T cells were stimulated by both 3H1 and 3H1-derived peptides.
      Interleukin 2, interleukin 4, and IFN-gamma were assayed in the culture medium of
      peripheral blood mononuclear cells stimulated with 3H1, CEA, and LCD-2 to
      determine the T-cell helper subset induced by these stimulants. The in vitro
      responses were mainly associated with secretion of IFN-gamma, which suggested
      that the induced T cells were most likely CD4+ Th1 type. Future studies will
      include the design of second-generation LCD-2 and CEA peptides to further enhance
      antigenicity, to characterize the responding T-cell populations more fully, and
      to test refined peptides for immunogenicity.

PMID- 9515809
TI  - Interleukin 12 gene therapy of MHC-negative murine melanoma metastases.
AB  - Immunological gene therapy of cancer relies heavily on the activation of T cells,
      but tumors with defects in MHC gene expression are not recognized by MHC
      restricted T cells. To investigate the potential of cytokine genes for the
      therapy of MHC-negative tumors, we transduced B78H1, a class I-negative murine
      melanoma clone, with a polycistronic vector carrying murine interleukin (IL)-12
      genes. The clones studied produced 400-25,000 pg/ml IL-12; their in vitro growth
      properties were similar to those of parental cells. A complete inhibition of
      growth was observed in vivo both after s.c. and i.v. administration of all IL-12
      clones. IL-12-transduced cells were also used as a therapeutic vaccine in mice
      bearing micrometastases by nontransduced parental cells. A significant (80-90%)
      reduction in the number of lung nodules was obtained. Immunohistochemical
      analysis and studies in immunocompromised hosts showed that T cells and natural
      killer cells had a significant role in the elimination of IL-12-releasing cells.
      In situ hybridization with cytokine probes detected a strong increase in the
      proportion of leukocytes positive for IFN-gamma, tumor necrosis factor alpha, IL
      1beta, and IFN-inducible protein 10 at the site of rejection of IL-12-engineered
      tumor cells. However, it was clear that the loss of in vivo growth was also due
      to T-cell- and natural killer cell-independent factors, possibly related to the
      antiangiogenic properties of IL-12. In conclusion, tumor therapy based on IL-12
      gene transduction was effective on a MHC-negative metastatic tumor, suggesting a
      possible application to MHC-defective human neoplasms.

PMID- 9515810
TI  - Frequent deletion and 5' CpG island methylation of the p16 gene in primary
      malignant lymphoma of the brain.
AB  - A total of 10 primary malignant lymphomas of the brain were examined for
      deletion, mutation, and 5' CpG island methylation of the p16 gene, which is a
      candidate tumor suppressor gene with CDK-inhibitory function. In Southern blot
      analysis, p16 gene deletion was suggested in nine cases, homozygously (five
      cases) or hemizygously (four cases). In the remaining one case, p16 gene deletion
      was not suggested. Although single-strand conformation polymorphism and
      nucleotide analyses suggested no mutations of the p16 gene in these cases,
      methylation analyses revealed 5' CpG island methylation in three cases, of which
      two were those with presumed hemizygous deletion and one was that without
      deletion in Southern blot analysis. Thus, p16 gene abnormality was detected in
      all 10 of the brain lymphomas examined, and in 8 of them, actual p16 gene
      inactivation was suggested by their homozygous deletion (5 cases) or 5' CpG
      island methylation (3 cases). These findings suggest that p16 gene abnormality
      and inactivation are closely related to carcinogenesis in primary malignant
      lymphoma of the brain. The p15 gene, another candidate tumor suppressor gene
      located in the vicinity of the p16 gene, to which it shows structural and
      functional similarity, was also presumed to be deleted similarly in most cases.
      Its methylation was seen in one case, the case without the methylated p16 gene.

PMID- 9515811
TI  - Transcription of a novel mouse semaphorin gene, M-semaH, correlates with the
      metastatic ability of mouse tumor cell lines.
AB  - In the attempt to identify genes associated with metastasis, we have compared
      gene expressions of two metastatic cell lines, 4T1 and 66cl4, and one
      noninvasive, nonmetastatic cell line, 67NR, which originate from the same mouse
      mammary adenocarcinoma. Using the technique of differential display, we
      identified a novel member of the semaphorin/collapsin family in the two
      metastatic cell lines. We have named it M-semaH. Northern hybridization to a
      panel of tumor cell lines revealed transcripts in 12 of 12 metastatic cell lines
      but in only 2 of 6 nonmetastatic cells and none in immortalized mouse
      fibroblasts. To our knowledge, this is the first time that the expression of a
      semaphorin gene has been shown to correlate positively with tumor progression. We
      have characterized two transcripts present in the tumor cells. One transcript, M
      semaH-v, is a putative splice variant, which is less abundant in normal tissue
      and lacks 478 bp in the 3' untranslated region. Both transcripts encode the same
      775 amino acids with the features of a secreted glycoprotein. Northern analysis
      suggests that the M-semaH gene is involved in embryonic development and in situ
      hybridization locates the M-semaH expression to the developing lungs, to
      developing skeletal elements, and to the ventral horns of the developing neural
      tube.

PMID- 9515812
TI  - The role of DNA methylation in expression of the p19/p16 locus in human bladder
      cancer cell lines.
AB  - Methylation of CpG sites in the control regions of tumor suppressor genes may be
      an important mechanism for their heritable, yet reversible, transcriptional
      inactivation. These changes in methylation may impair the proper expression
      and/or function of cell cycle regulatory genes and confer a selective growth
      advantage to affected cells. Detailed methylation analysis using genomic
      bisulfite sequencing was performed on a series of subclones of a bladder cancer
      cell line in which a hypermethylated p16 gene had been reactivated by transient
      treatment with 5-aza-2'-deoxycytidine. Methylation of the CpG island in the
      promoter of the p16 gene in human bladder cancer cells did not stop the formation
      of a transcript initiated 20 kb upstream by the p19 promoter but did prevent the
      expression of a p16 transcript. Furthermore, we show that reactivant clones that
      expressed p16 at varying levels contained heterogeneous methylation patterns,
      suggesting that p16 expression can occur even in the presence of a relatively
      heavily methylated coding region. We also present the first functional evidence
      that methylation of only a small number of CpG sites can significantly down
      regulate p16 promoter activity, thus providing support for the model of
      progressive inactivation of this tumor suppressor gene by DNA methylation.

PMID- 9515813
TI  - Antitumor effect of a farnesyl protein transferase inhibitor in mammary and
      lymphoid tumors overexpressing N-ras in transgenic mice.
AB  - We tested the antineoplastic effect of the farnesyltransferase inhibitor L
      744,832 in mammary and lymphoid tumors overexpressing the N-ras proto-oncogene in
      transgenic mice. Mice bearing mammary tumors were randomly assigned to receive
      daily 40 mg/kg s.c. injections of this compound (experimental group, n = 6) or
      vehicle (control group, n = 6) per day for 5.5 weeks. Treatment with the compound
      significantly reduced the mammary tumor mean growth rate in the experimental
      group (-0.7 mm3/day), as compared with the control group (+28.2 mm3/day; P <
      0.001). There was a significant difference in lymphoma incidence at the end of
      the treatment between the experimental (0 of 6) and the control (3 of 6) groups
      (P < 0.05). Therefore, this compound is effective in treating in vivo mammary
      carcinomas and lymphomas in which an activated N-Ras pathway drives
      tumorigenesis. The number of apoptotic figures in mammary tumors was
      significantly higher (P = 0.04) in the experimental (14.7 +/- 8.1) than it was in
      the control (5.7 +/- 3.5) group, indicating that apoptotic induction could
      contribute to the mechanism of antitumor activity of this compound. We analyzed
      the level of processing of N-Ras and H-Ras after immunoprecipitation and Western
      blotting of protein extracts obtained from mammary tumors treated with L-744,832
      or vehicle, either in vivo or in vitro (after primary culture of the same
      tumors), and from several in vitro treated control cell lines. In all compound
      treated mammary tumors and cell lines, H-Ras was mostly unprocessed (more so
      after in vitro than after in vivo treatment), whereas N-Ras remained mostly
      processed. Both H-Ras and N-Ras remained fully processed in all vehicle-treated
      samples. These findings are consistent with a less intense antineoplastic effect
      of the treatment with the compound in our N-ras model than the effect previously
      reported for the same compound in H-ras transgenics. In addition, the finding
      that, in compound-treated mammary tumors, the N-Ras protein remains mainly
      processed suggests that, in our model, other proteins in addition to Ras may be a
      target for the compound. Our results and the previous findings of frequent N-ras
      activation in human hematopoietic malignancies support a role for L-744,832 in
      the treatment of lymphomas and of mammary carcinomas with an activated N-Ras
      pathway, as well as the testing of a farnesyl protein transferase inhibitor in
      humans to establish its clinical relevance.

PMID- 9515814
TI  - Mutations of the bacteriophage T4 type II DNA topoisomerase that alter
      sensitivity to antitumor agent 4'-(9-acridinylamino)methanesulfon-m-anisidide and
      an antibacterial quinolone.
AB  - Various antitumor and antibacterial agents target type II DNA topoisomerases,
      stabilizing a cleaved DNA reaction intermediate and thereby converting
      topoisomerase into a cellular poison. Two 4'-(9-acridinylamino)methanesulfon-m
      anisidide (m-AMSA)-resistant bacteriophage T4 topoisomerases have previously been
      characterized biochemically, and we have now determined the sequence of the
      causative mutations. In one case, a mutation (E457K) in a conserved domain of
      gp39 (ATPase subunit) causes resistance to antitumor agent m-AMSA but
      hypersensitivity to the quinolone oxolinic acid. In the second case, a
      combination of two amino acid substitutions (S79F and G269V) in gp52 (DNA
      cleaving subunit) causes resistance to both m-AMSA and oxolinic acid. The S79F
      mutation is responsible for drug resistance, whereas the G269V mutation
      suppresses a topoisomerase deficiency caused by S79F. Surprisingly, the G269V
      mutation by itself causes a dramatic hypersensitivity to both inhibitors,
      defining a new class of topoisomerase mutants. Because S79 and the adjacent N78
      are homologous to two key residues of DNA gyrase that affect quinolone
      sensitivity, we generated additional amino acid substitutions at these two
      positions. The substitutions alter sensitivity to m-AMSA and to oxolinic acid,
      sometimes in opposite directions. Furthermore, the quinolone sensitivities of the
      various mutants paralleled those of corresponding gyrase mutants. These results
      support models in which both quinolones and antitumor agents bind to a conserved
      site that overlaps the active site of the enzyme.

PMID- 9515815
TI  - Mutational spectra of a 100-base pair mitochondrial DNA target sequence in
      bronchial epithelial cells: a comparison of smoking and nonsmoking twins.
AB  - Seventeen separate mitochondrial hot spot mutations in a 100-bp target sequence
      (mitochondrial bp 10,030-10,130) were detected and measured in bronchial
      epithelial cell samples isolated from smokers and nonsmokers. Among the
      individuals sampled were three pairs of monozygotic twins in which one twin had
      never smoked and had a nonsmoking spouse, and the other had a smoking history of
      >10 pack-years. Individual point mutations present at frequencies as low as 10(
      6) were detected. Partially denaturing electrophoresis was used to separate
      mutant from nonmutant sequences on the basis of their melting temperatures, and
      the target sequence was subsequently amplified via high-fidelity PCR with Pfu DNA
      polymerase. Tests were performed to determine whether mismatch intermediates or
      DNA adducts present in the cellular DNA were converted to mutants during PCR. Hot
      spot mutations were clearly observed in bronchial epithelial cells, and the same
      hot spots were observed consistently in different samples. Significant numerical
      variability in the mutant fractions for individual mutants was observed among
      samples and are ascribed to unequal mitochondrial segregation in stem and
      transition cells. The mutational spectra in smokers' samples did not differ
      significantly from the mutational spectra in nonsmokers' samples for this 100 bp
      of mitochondrial DNA. No smoking-specific hot spots were detected. The overall
      mutant fractions in smokers' samples were not elevated compared to those of
      nonsmokers. As much variability was observed between two samples from the same
      individual's lung as between a sample from a smoker and a sample from a
      nonsmoker. These findings demonstrate that inhaled tobacco smoke does not induce
      prominent point mutations in this 100-bp target mitochondrial sequence in
      smokers' bronchial epithelial cells. Endogenous factors (e.g., DNA replication
      errors or DNA damage by endogenous reactive chemicals) are suggested to be more
      likely to represent the most important contributors to mitochondrial mutagenesis.

PMID- 9515816
TI  - Vascular permeability factor/vascular endothelial growth factor-mediated
      signaling in mouse mesentery vascular endothelium.
AB  - Vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) is a
      multifunctional cytokine and growth factor that has important roles in both
      pathological and physiological angiogenesis. VPF/VEGF induces vascular
      hyperpermeability, cell division, and other activities by interacting with two
      specific receptor tyrosine kinases, KDR/Flk-1 and Flt-1, that are selectively
      expressed on vascular endothelium. The signaling cascade that follows VPF/VEGF
      interaction with cultured endothelium is only partially understood but is known
      to result in increased intracellular calcium, activation of protein kinase C, and
      tyrosine phosphorylations of both receptors, phospholipase C-gamma (PLC-gamma)
      and phosphatidylinositol 3'-kinase. For many reasons, signaling events elicited
      in cultured endothelium may not mimic mediator effects on intact normal or tumor
      induced microvessels in vivo. Therefore, we developed a system that would allow
      measurement of VPF/VEGF-induced signaling on intact microvessels. We used mouse
      mesentery, a tissue whose numerous microvessels are highly responsive to VPF/VEGF
      and that we found to express Flk-1 and Flt-1 selectively. At intervals after
      injecting VPF/VEGF i.p., mesenteries were harvested, extracted, and
      immunoprecipitated. Immunoblots confirmed that VPF/VEGF induced tyrosine
      phosphorylation of several proteins in mesenteric microvessels as in cultured
      endothelium: Flk-1; PLC-gamma; and mitogen-activated protein kinase. Similar
      phosphorylations were observed when mesentery was exposed to VPF/VEGF in vitro,
      or when mesenteries were harvested from mice bearing the mouse ovarian tumor
      ascites tumor, which itself secretes abundant VPF/VEGF. Other experiments further
      elucidated the VPF/VEGF signaling pathway, demonstrating phosphorylation of both
      PYK2 and focal adhesion kinase, activation of c-jun-NH2-kinase with
      phosphorylation of c-Jun, and an association between Flk-1 and PLC-gamma. In
      addition, we demonstrated translocation of mitogen-activated protein kinase to
      the cell nucleus in cultured endothelium. Taken together, these experiments
      describe a new model system with the potential for investigating signaling events
      in response to diverse mediators on intact microvessels in vivo and have further
      elucidated the VPF/VEGF signaling cascade.

PMID- 9515817
TI  - Reduced lysyl oxidase messenger RNA levels in experimental and human prostate
      cancer.
AB  - To identify genes associated with prostate cancer progression, we developed a
      strategy involving the use of differential display PCR and a panel of genetically
      matched primary tumor- and metastasis-derived mouse prostate cancer cell lines.
      We analyzed sequences that were differentially stimulated by transforming growth
      factor-beta1 in primary tumor-versus metastasis-derived cell lines, based on our
      previous studies indicating that acquisition of differential responses to this
      growth factor could result in phenotypic traits that facilitate tumor metastasis
      from specific cell clones within the primary tumor. Using this system, we
      isolated and sequenced a cDNA fragment that encoded mouse lysyl oxidase (LO) and
      was induced by transforming growth factor-beta1 in primary tumor but not in
      metastasis-derived cells. Northern blotting analysis revealed increased LO
      expression in a panel of primary tumor cell lines but significantly reduced or
      nondetectable expression in their matched metastatic counterparts. Further in
      situ hybridization analysis revealed LO expression in normal mouse prostate
      epithelium but, in most cases, progressive loss of expression in primary prostate
      cancer and associated metastatic lesions. Importantly, in situ hybridization
      studies of normal human prostate and prostate malignancies revealed a similar
      loss of expression during progression to metastasis. The progressive loss of LO
      expression during prostate cancer progression provides information that may
      increase our understanding of the mechanisms that underlie this disease. In
      addition, LO may provide a useful molecular marker and/or establish a novel
      therapeutic target for prostate cancer.

PMID- 9515818
TI  - Uroplakin II gene is expressed in transitional cell carcinoma but not in
      bilharzial bladder squamous cell carcinoma: alternative pathways of bladder
      epithelial differentiation and tumor formation.
AB  - Uroplakins (UPs) are integral membrane proteins that are synthesized as the major
      differentiation products of mammalian urothelium. We have cloned the human UP-II
      gene and localized it on chromosome 11q23. A survey of 50 transitional cell
      carcinomas (TCCs) revealed a UP-II polymorphism but no tumor-specific mutations.
      Immunohistochemical staining using rabbit antisera against a synthetic peptide of
      UP-II and against total UPs showed UP reactivity in 39.5% (17 of 43 cases) of
      conventional TCCs, 12.8% (5 of 39) of bilharzial-related TCCs, and 2.7% (1 of 36)
      of bilharzial-related squamous cell carcinomas (SCCs). The finding that fewer
      bilharzial TCCs express UPs than conventional TCCs (12.8 versus 40%) raised the
      possibility that the former are heterogeneous, expressing SCC features to varying
      degrees. Our data strongly support the hypothesis that urothelium can undergo at
      least three pathways of differentiation: (a) urothelium-type pathway; (b)
      epidermis-type pathway; and (c) glandular-type pathway, characterized by the
      production of UPs, K1/K10 keratins, and secreted glycoproteins, respectively.
      Vitamin A deficiency and mesenchymal factors may play a role in determining the
      relative contributions of these pathways to urothelial differentiation as well as
      to the formation of TCC, SCC, and adenocarcinoma, or a mixture thereof.

PMID- 9515819
TI  - Molecular mediators of angiogenesis in bladder cancer.
AB  - Bladder tumors are characterized by markedly increased angiogenesis when compared
      to the normal urothelium (NU) from which they are derived. Here, we use both
      cultured cells and immunohistochemistry to demonstrate a primary regulatory role
      for thrombospondin-1 (TSP-1), a potent inhibitor of angiogenesis, in the
      development of bladder tumor angiogenesis. Secretions from bladder cancer (CA)
      cells stimulated endothelial cell migration and corneal neovascularization,
      whereas those from NU cells were inhibitory. The antiangiogenic activity of NU
      cells was primarily due to secreted TSP-1 because neutralizing antibodies
      completely relieved the inhibition. Neutralizing antibodies to several putative
      angiogenesis inducers identified vascular endothelial growth factor (VEGF) and,
      to a lesser extent, basic fibroblast growth factor as the primary inducers
      secreted by bladder cancer cells. The secretion of TSP-1 by low- and high-grade
      cancer cells was reduced >94% when compared to NU cells, and this loss of
      inhibitory TSP-1 accounted for the development of an angiogenic phenotype because
      both NU cells and cancer cells secreted similar levels of total stimulatory
      activity and VEGF. Immunohistochemistry showed that TSP-1 was significantly
      reduced in all grades of bladder cancer when compared to NU, whereas VEGF
      staining remained relatively constant. Taken together, these data suggest that
      down-regulation of TSP-1 secretion is a key event in the switch from an
      antiangiogenic to an angiogenic phenotype, which occurs early in the development
      of bladder cancer.

PMID- 9515820
TI  - Differential regulation of cyclin-dependent kinase inhibitors in monolayer and
      spheroid cultures of tumorigenic and nontumorigenic fibroblasts.
AB  - The Ras proto-oncogene has been implicated in the in vivo development of tumors
      and in the in vitro transformation of cultured cell lines. In both of these
      conditions, Ras-mediated disruption of cell cycle-regulatory mechanisms leads to
      unregulated cellular proliferation, although the exact mechanisms by which Ras
      accomplishes this are not clear. Using as a model the M1 and MR1 rat fibroblast
      cell lines, which differ in the expression of a regulated Ras (M1 cells) versus a
      constitutively active Ras (MR1 cells), we examined the role of Ras in the control
      of cellular proliferation in two-dimensional (monolayer) and three-dimensional
      (spheroid) cell cultures. These cell lines are very similar in their monolayer
      growth characteristics, but M1 cells will arrest their cell cycle progression in
      aggregate culture, whereas MR1 cells proliferate normally as small spheroids. We
      report here that G1-phase arrest in plateau-phase monolayer cultures of both M1
      and MR1 cells correlates with up-regulated expression of the cyclin-dependent
      kinase (CDK) inhibitor p18INK4c. Enhanced p18INK4c expression was also observed
      in G1-arrested M1 cells cultured as multicellular spheroids but was not induced
      in small proliferating MR1 multicellular spheroids. The kinetics of G1 arrest in
      M1 cells after inoculation into aggregate culture correlated well with the
      induction of p18INK4c expression. Conversely, resumption of proliferation in
      monolayer culture of arrested M1 cells isolated from spheroids coincided with the
      loss of expression of p18INK4c. After extended culture, cells in the inner region
      of MR1 spheroids arrested in the G1 phase without any up-regulation of p18INK4c
      expression. In this case, the CDK inhibitor p21(Cip1/Waf1) was selectively
      induced in the inner regions of large MR1 spheroids, concomitant with a decrease
      in cyclin and CDK expression. Thus, Ras-dependent regulation of p18INK4c
      expression seems to control the ability of rat embryo fibroblasts to proliferate
      as small multicellular aggregates, whereas p21(Cip1/Waf1) expression seems to
      regulate the G1-phase arrest induced by the stressful microenvironment found
      within the inner region of large spheroids.

PMID- 9515821
TI  - Differential expression of a truncated form of the urokinase-type plasminogen
      activator receptor in normal and tumor thyroid cells.
AB  - We studied the urokinase-type plasminogen activator (uPA) receptor (uPA-R) in
      normal and neoplastic human thyroid cells. It has recently been shown that
      cleaved forms of uPA-R display an extremely strong chemotactic activity. Normal
      human thyroid TAD-2 cells express the intact form of the uPA-R and a truncated
      form lacking the uPA-binding domain on their surface, in a similar manner to
      tumor thyroid cell lines. However, in tumor thyroid cell lines, the amount of the
      truncated form is variable: high in papillary carcinoma cells, very low in
      follicular carcinoma cells, and not detectable in anaplastic carcinoma cells.
      Similar studies on primary cell cultures confirm the presence of the truncated
      form of uPA-R in normal and in papillary carcinoma cells and its partial or total
      loss in follicular carcinoma cells. The presence of truncated uPA-R correlates to
      uPA secretion, except in papillary carcinoma cells, which express the truncated
      form of uPA-R but do not release uPA. uPA-R is also able to act as an adhesion
      receptor by binding vitronectin (VTN) and interacting with integrins. We observe
      that removal of uPA-R from the surface of normal thyroid and anaplastic carcinoma
      cells by phosphatidylinositol-specific phospholipase C or treatment with anti-uPA
      R antibodies decreases the adhesion of both cell types to VTN and, less
      efficiently, to fibronectin or collagen. On the other hand, uPA treatment
      strongly increases the adhesion of anaplastic carcinoma cells specifically to
      VTN.

PMID- 9515822
TI  - Funding for biomedical research: What happened to our share of the nation's
      wealth?

PMID- 9515823
TI  - What happens in the Dead Sea?

PMID- 9515824
TI  - Right ventricular function in COPD: can it be assessed reliably by the
      measurement of right ventricular ejection fraction?

PMID- 9515825
TI  - Staffing ICUs: the good news and the not-so-good news.

PMID- 9515826
TI  - Rehabilitation of hypoxemic patients with COPD at low altitude at the Dead Sea,
      the lowest place on earth.
AB  - BACKGROUND: In patients with COPD, oxygen therapy has been shown to improve
      exercise capacity and survival. Increase in barometric pressure at low altitude
      can serve as a simple way to improve arterial oxygenation in hypoxemic patients.
      We have tried to evaluate the effect of staying at low altitude on arterial
      oxygenation and exercise performance in patients with COPD. PATIENTS AND METHOD:
      Eleven patients with COPD (9 male, 2 female) aged 38 to 79 years (mean FEV1, 0.96
      L; 36% predicted) with hypoxemia (mean PaO2, 54.2+/-8.9 mm Hg) at Jerusalem
      (altitude 800 m above sea level) were taken down to the Dead Sea area (altitude
      402 m below sea level) for 3 weeks. At both locations we tested arterial blood
      gases, spirometry, progressive exercise, 6-minute walking distance, and sleep
      oximetry. The study was repeated 2 weeks after returning to Jerusalem. RESULTS:
      Spirometry results were unchanged. Mean arterial PaO2 rose from 54.2+/-8.9 mm Hg
      to 69.5+/-11 at the first week and to 66.6+/-11 at the third week of stay
      (p<0.001). PaCO2 rose from 43.5+/-9.8 mm Hg to 47.7+/-9 and 49.5+/-8.4 (p<0.006).
      Six-minute walking distance rose from 337+/-107 m to 449+/-73 and 507+/-91 in the
      third week (p<0.005). Maximum oxygen consumption (VO2max) rose from 901+/-257
      mL/min to 1,099+/-255 and 1,063+/-250 mL/min (p=0.01). Sleep oximetry showed an
      increase in mean sleep arterial oxygen saturation from 86.0+/-4.3% to 89.9+/-4.2%
      and 88.3+/-3.0 at 1 and 3 weeks, respectively (p<0.05). Following the return to
      Jerusalem, arterial gases returned to their baseline levels (PaO2, 52.9+/-9.4 mm
      Hg) but 6-min walking distance remained significantly high, 453+/-47 (p<0.02),
      and VO2max remained high as well (1,102+/-357 mL/min), although it did not reach
      statistical significance. CONCLUSIONS: Decline to low altitude or staving at high
      oxygen environment improves arterial oxygenation and exercise capacity in
      hypoxemic patients residing in moderate or high altitude. Low altitude (or
      pressurized wards) can improve pulmonary rehabilitation of hypoxemic patients
      with COPD.

PMID- 9515827
TI  - Right and left ventricular dysfunction in patients with severe pulmonary disease.
AB  - OBJECTIVE: To determine the prevalence of right and left ventricular dysfunction
      in a prescreened population of patients with severe pulmonary disease, and to
      analyze the relationship between right and left ventricular function. DESIGN:
      Retrospective record review of 434 patients with severe pulmonary disease.
      PATIENTS: Patients with end-stage pulmonary disease, including alpha1-antitrypsin
      deficiency emphysema, COPD, cystic fibrosis (CF), idiopathic pulmonary fibrosis,
      and pulmonary hypertension (primary and Eisenmenger's syndrome), who were
      evaluated for lung transplantation between January 1993 and December 1995.
      MEASUREMENTS: Pulmonary function tests, arterial blood gases, radionuclide
      ventriculography, two-dimensional transthoracic echocardiography, pulmonary
      hemodynamics, coronary angiography. RESULTS: Right ventricular dysfunction (right
      ventricular ejection fraction [RVEF] <45%) was present in 267 patients (66%), but
      the prevalence was highest (94%) in patients with pulmonary vascular disease.
      Among the patients with airway or parenchymal lung disease, the prevalence ranged
      from 59% in COPD to 66% in CF. In contrast, left ventricular dysfunction (left
      ventricular ejection fraction [LVEF] <45%) was present in only 6.4%, but it, too,
      was most common in the group with pulmonary hypertension (19.6%). In the groups
      with parenchymal or airway disease, the prevalence was 3.6%, and there was no
      statistical difference among the four diagnoses (alpha1-antitrypsin deficiency
      emphysema; COPD; CF; idiopathic pulmonary fibrosis). LVEF showed a significant
      correlation with RVEF (r=0.44; p<0.05), and left ventricular dysfunction was
      associated with the presence of moderate-to-severe tricuspid regurgitation but
      not with coronary artery disease. In a subset of patients with both right and
      left ventricular dysfunction who subsequently underwent lung transplantation,
      RVEF and LVEF increased pari passu after transplantation. CONCLUSION: The
      prevalence of right ventricular dysfunction is high in patients with end-stage
      pulmonary disease, but the prevalence of left ventricular dysfunction is
      relatively low. Left ventricular dysfunction appears to be related to right
      ventricular dysfunction, perhaps through ventricular interdependence.

PMID- 9515828
TI  - Short-term growth in asthmatic children using fluticasone propionate.
AB  - BACKGROUND: Inhaled corticosteroids may reduce short-term growth velocity in
      asthmatic children and knemometry is the most sensitive tool to detect this short
      term growth suppression. STUDY OBJECTIVE: To compare lower leg growth velocity,
      as measured by knemometry, in asthmatic children during and after treatment with
      inhaled fluticasone propionate (FP), 100 microg twice daily. DESIGN:
      Nonrandomized open trial. SETTING: University hospital, outpatient clinic for
      pediatric pulmonology. PATIENTS: Twenty-one asthmatic children (13 boys), aged 6
      to 10 years. INTERVENTIONS: Inhalation of FP from a dry powder inhaler, 100
      microg, twice daily for 6 weeks, followed by 2 weeks during which only an inhaled
      beta2-agonist was used on demand (washout). During treatment and washout periods,
      patients were seen every 2 weeks at the same time of day. MEASUREMENTS AND
      RESULTS: Lower leg growth velocity measured by knemometry during FP treatment was
      not significantly different from that during washout (p=0.33, one-way analysis of
      variance). CONCLUSIONS: No significant suppression of lower leg growth velocity
      was found in prepubertal asthmatic children using FP, 100 microg, by dry powder
      inhaler twice daily for 6 weeks.

PMID- 9515829
TI  - Perception of the role and potential side effects of inhaled corticosteroids
      among asthmatic patients.
AB  - BACKGROUND: Misunderstanding of the role of asthma medication and fear of
      untoward side effects may reduce compliance to therapy, potentially resulting in
      poor asthma control and increased risk of severe asthma events. METHODS: We
      report the results of a recent Canadian survey of 603 asthmatic patients
      recruited from the general population, aimed at determining their perception of
      the role and potential side effects of inhaled corticosteroids (ICS). RESULTS:
      The survey revealed that a large proportion of asthmatic patients do not
      understand the role of their medications and have many misconceptions and fears
      in regard to ICS, reducing their willingness to use them. Among the most common
      fears are those concerning troublesome side effects, particularly in regard to
      corporeal image, bone density, and a reduction in efficacy of medication over
      time. More than half of the population said they were very or somewhat concerned
      using ICS on a regular basis; two thirds of patients had not discussed their
      concerns about ICS with their physicians or other health-care professionals.
      Finally, in a large number of asthma patients, asthma was not adequately
      controlled, according to recent asthma consensus guidelines. CONCLUSIONS: These
      observations stress the importance for those involved in asthma care of
      questioning patients about their understanding of the role of asthma medications,
      particularly ICS, their fears and misconceptions, and what they consider to be
      adequate asthma control, in order to provide appropriate education and
      counseling.

PMID- 9515830
TI  - Therapeutic response patterns to high and cumulative doses of salbutamol in acute
      severe asthma.
AB  - STUDY OBJECTIVES: To examine the main therapeutic response patterns to high doses
      of salbutamol and to determine the factors that contribute to outcome in acute
      severe asthma. SETTING: The emergency department (ED) of a large, urban hospital
      with primary and referral care responsibilities. PATIENTS AND DESIGN: One hundred
      sixteen consecutive patients with acute exacerbations of asthma were enrolled in
      the trial, using a prospective sequential design. INTERVENTIONS: All patients
      were treated with salbutamol delivered with a metered-dose inhaler into a spacer
      device in four puffs (400 microg) at 10-min intervals. The protocol involved 3 h
      of this treatment (1,200 microg each 30 min). MEASURES AND RESULTS: A dose
      response increase in pulmonary function was found, but only 70% improved
      sufficiently to be discharged. Of these, almost 70% required < or =2.4 mg of the
      drug within 1 h to reach the discharge threshold, whereas the remainder 30% need
      > or =3.6 mg. In 30% of subjects, salbutamol was ineffective. These patients were
      characterized by a more severe disease as judged by previous beta2-agonist use,
      larger duration of attack before ED visit, and a more severe obstruction at
      presentation. However, the most important predictors of outcome were peak
      expiratory flow rate (PEFR) as percent of predicted, PEFR as liters per minute,
      and PEFR variation over baseline value, all at 30 min. CONCLUSIONS: This study
      described two different therapeutic response patterns to salbutamol. Almost 70%
      of patients were sensitive to salbutamol (good response pattern), and in this
      group, 2.4 to 3.6 mg represents optimal treatment. In the remainder 30% of
      patients (poor response pattern), salbutamol in high doses had little effect.
      However, the outcome was not determined by the intensity of the initial symptoms
      or by the value of the presenting PEFR, but rather by the early (30 min) short
      term response to treatment.

PMID- 9515831
TI  - The effects of body composition changes to observed improvements in
      cardiopulmonary parameters after exercise training with cardiac rehabilitation.
AB  - STUDY OBJECTIVE: To discriminate the effects of body fat reduction on
      improvements in peak aerobic capacity made following exercise training during
      cardiac rehabilitation. DESIGN: Observational, prospective study. SETTING:
      Outpatient cardiovascular health center at regional academic center. PATIENT
      INTERVENTIONS: Peak oxygen uptake (pkVO2), percent body fat, lean body mass
      (LBM), and other anthropometric measures were assessed before and after a 3-month
      program of cardiac rehabilitation and exercise training in 500 consecutive
      cardiac patients following a major coronary event. Baseline pkVO2 was corrected
      for LBM (pk/VO2 lean) and compared with posttraining values. RESULTS: Following
      exercise training, percent body fat decreased 5% from 26.2+/-8.0 to 24.8+/-7.5
      (p<0.0001), and LBM increased 1% from 61.3+/-12.5 to 61.7+/-11.8 kg (p=0.02).
      pk/VO2 increased 16% from 16.0+/-4.1 to 18.5+/-4.8 mL/kg/min (p<0.0001), and
      pkVO2 lean increased 13% from 21.7+/-5.3 to 24.6+/-6.0 mL/kg/min (p<0.0001).
      Isolating the effects of reduction in body fat, we discern that these changes
      contributed to 0.3 of the 2.5 mL/kg/min increase in pkVO2 or 12% of the increase
      in pkVO2 observed. CONCLUSIONS: Changes in body composition, as a consequence of
      dietary and exercise modification, contribute to 12% of the "observed"
      improvement noted in weight-adjusted peak aerobic capacity following cardiac
      rehabilitation and exercise training. Changes in pkVO2 lean should be used by
      investigators to assess the singular effects of exercise conditioning alone.

PMID- 9515832
TI  - Comparison of pulmonary gas exchange measurements between incremental and
      constant work exercise above the anaerobic threshold.
AB  - STUDY OBJECTIVES: To compare arterial blood gas (ABG) and pulmonary gas exchange
      variables (alveolar-arterial oxygen pressure difference [P(A-a)O2] and
      physiologic dead space to tidal volume ratio [VD/VT]) measured during incremental
      exercise test (IET) and constant work (CW) exercise at a matched oxygen uptake
      (VO2). DESIGN: A comparison of IET and CW variables was accomplished using
      patient data from clinical referrals for cardiopulmonary exercise testing and
      control data not reported from a previous study. SETTINGS: El Paso, Tex, located
      at an altitude of 1,270 m (barometric pressure, 656 mm Hg). PARTICIPANTS: Sixteen
      patients with dyspnea on exertion/exercise intolerance and nine normal subjects
      were evaluated above the anaerobic threshold (AT); seven patients were also
      studied below the AT. INTERVENTIONS: Participants had a maximal IET followed in 1
      h by a 5-min CW test. Arterial blood samples were obtained from a radial catheter
      every other minute during IET and during minute 5 of CW. Cardiopulmonary
      measurements were obtained using an automated system in a breath-by-breath
      fashion (60-s averaging). RESULTS: Above the AT, no differences were observed in
      normal subjects between IET and CW at a matched VO2 in the following: PaO2 (79 vs
      79 mm Hg); arterial oxygen saturation (SaO2) (94% vs 94%); P(A-a)O2 (16 vs 16 mm
      Hg); and VD/VT (0.09 vs 0.09) (mean values). Similarly, no differences were
      observed in patients above the AT in PaO2 (69 vs 68), SaO2 (90 vs 90), and VD/VT
      (0.24 vs 0.23). PaCO2 was 2 mm Hg higher (36 vs 34) in normal subjects and in
      patients (34 vs 32) during IET. A significant (p<0.05), albeit clinically
      unimportant, difference was also observed in P(A-a)O2 (28 vs 29) in patients. No
      statistically significant differences were observed below the AT between IET and
      CW for any of the variables measured. CONCLUSIONS: These data demonstrate the
      reliability of ABG and pulmonary gas exchange variables measured during 1-min IET
      for clinical use in patients and normal subjects. However, PaCO2 tends to be
      slightly higher during IET vs CW.

PMID- 9515833
TI  - Interpretive algorithms for the symptom-limited exercise test: assessing dyspnea
      in Persian Gulf war veterans.
AB  - Interpretation of symptom-limited exercise testing requires analysis of a large
      body of simultaneously recorded cardiopulmonary data. Karlman Wasserman has
      recommended an algorithmic approach to interpretation (WA) that leads to a
      dichotomous choice between pulmonary and cardiovascular impairment. An
      alternative algorithm published by William Eschenbacher (EA) provides for
      concurrent assessment of cardiovascular and pulmonary exercise impairment. We
      analyzed a group of 29 individuals referred to the Pulmonary Physiology
      Laboratory at the Washington Veterans Affairs Medical Center for evaluation of
      dyspnea following service in the Persian Gulf War to assess the concordance of
      the two algorithms in determining the cause of dyspnea and exercise impairment in
      these individuals. They each performed a progressive, ramped, symptom-limited
      exercise test on a bike for a minimum of 6 min. Exercise measurements were
      analyzed by both interpretive algorithms. Concordance was found in 28% of tests.
      The greatest discordance occurred in identifying pulmonary limitation. Eleven had
      pulmonary limitation by EA; of these, WA found 1 to have pulmonary limitation, 5
      to be normal, 4 indeterminate, and 1 musculoskeletal limitation. Of the 11 with
      pulmonary limitation by EA, but not by WA, 5 had abnormal resting pulmonary
      function measurements. Analysis of the differences between these two interpretive
      approaches is given. The EA algorithm may be more sensitive for detecting
      exercise impairment of pulmonary origin, but its specificity remains to be
      determined.

PMID- 9515834
TI  - Validation of a new dyspnea measure: the UCSD Shortness of Breath Questionnaire.
      University of California, San Diego.
AB  - OBJECTIVE: Evaluate the reliability and validity of a new version of the
      University of California, San Diego Shortness of Breath Questionnaire (SOBQ), a
      24-item measure that assesses self-reported shortness of breath while performing
      a variety of activities of daily living. DESIGN: PATIENTS enrolled in a pulmonary
      rehabilitation program were asked to complete the SOBQ, the Quality of Well-Being
      Scale, the Center for Epidemiologic Studies Depression Scale, and a 6-min walk
      with modified Borg scale ratings of perceived breathlessness following the walk.
      SETTING: University medical center pulmonary rehabilitation program. PATIENTS:
      Thirty-two male subjects and 22 female subjects with a variety of pulmonary
      diagnoses: COPD (n=28), cystic fibrosis (n=9), and postlung transplant (n=17).
      MEASUREMENTS AND RESULTS: The current version of the SOBQ was compared with the
      previous version, the format of which often resulted in a significant number of
      "not applicable" answers. The results demonstrated that the SOBQ had excellent
      internal consistency (alpha=0.96). The SOBQ was also significantly correlated
      with all validity criteria. CONCLUSIONS: The SOBQ is a valuable assessment tool
      in both clinical practice and research in patients with moderate-to-severe lung
      disease.

PMID- 9515835
TI  - Evaluation of dyspnea during physical and speech activities in patients with
      pulmonary diseases.
AB  - STUDY OBJECTIVES: Dyspnea is most commonly assessed by questioning patients about
      their subjective perception of shortness of breath during physical exertion.
      Although speech production is altered by pulmonary disease, it has not been
      included in current dyspnea assessment tools. A questionnaire was developed to
      address reports of dyspnea during (1) physical activity, (2) speech activity, and
      (3) simultaneous speech and physical activity. DESIGN: An equal number of self-
      and experimenter-administered 30-item questionnaires was given to 203 patients
      with restrictive and obstructive pulmonary diseases. Their responses were
      analyzed statistically. RESULTS: The questionnaire had high internal consistency
      for individual items within each of the three sections. The sections were highly
      correlated but provided separate and distinct information. Factors extracted from
      each section were related to severity of dyspnea. Pairwise t tests demonstrated
      highly significant differences in subject responses to the three sections. The
      least dyspnea was experienced during speech activities, more during physical
      activities, and the most when speech and physical activities were combined.
      CONCLUSIONS: The questionnaire proved to be a quickly administered tool for
      providing information about the effect of dyspnea on activities of daily living.
      Because of the emphasis on dyspnea during speech production, it may be
      particularly useful for assessing patients who rely extensively on speaking
      ability for their livelihood.

PMID- 9515836
TI  - Predictors of quality of life and adjustment after lung transplantation.
AB  - STUDY OBJECTIVE: Few studies have examined predictors of quality of life and
      adjustment after lung transplantation. This study determined whether
      pretransplant psychological measures predicted physical health, quality of life,
      and overall adjustment posttransplant. Cross-sectional analyses also examined
      differences in adjustment and quality of life for lung transplant candidates and
      recipients. DESIGN AND PARTICIPANTS: Seventeen transplant candidates and 60
      transplant recipients completed questionnaires measuring adjustment and quality
      of life. In addition, we examined archival data on 107 transplant candidates who
      had received pretransplant psychological assessments, and posttransplant physical
      health status data were collected on these patients. Of the 107 patients who
      provided a pretransplant psychological assessment, 32 completed the
      questionnaires measuring posttransplant adjustment and quality of life. SETTING:
      University medical center transplant service. RESULTS: Cross-sectional analyses
      indicated significantly better adjustment and quality of life posttransplant.
      Pretransplant psychological variables were not associated with measures of
      posttransplant physical health. Hierarchical multiple regression analyses found
      that pretransplant anxiety and psychopathology predicted posttransplant
      adjustment (beta's ranging from 0.32 to 0.68) and greater pretransplant anxiety
      also predicted worse posttransplant quality of life (beta's ranging from 0.29 to
      0.62). Subjective sleep disturbances were associated with poorer adjustment and
      quality of life (beta's ranging from 0.36 to 0.75), and were found to mediate the
      relationship between presurgical anxiety and posttransplant adjustment and
      quality of life. CONCLUSIONS: This study found that psychological status
      pretransplant predicted adjustment and quality of life posttransplant. Moreover,
      increased anxiety levels pretransplant predicted subsequent subjective sleep
      disturbances, which were, in turn, associated with poorer adjustment and quality
      of life. The benefits of pretransplant stress management interventions are
      discussed.

PMID- 9515837
TI  - Early release of proinflammatory cytokines after lung transplantation.
AB  - BACKGROUND: Systemic hypotension may complicate the early postoperative period
      after lung transplantation. A release of proinflammatory cytokines secondary to
      lung ischemia/reperfusion injury could be involved in the pathogenesis of this
      early hemodynamic failure (EHF). STUDY OBJECTIVE: To assess prospectively whether
      the occurrence of EHF is associated with a release of cytokines in the systemic
      circulation. DESIGN: Blood samples were taken daily during the first
      postoperative week in 26 patients who underwent a double or a single-lung
      transplantation. These patients were divided into three groups: 7 patients who
      experienced EHF and subsequently died (EHF group); 15 patients without EHF
      (control group); and 4 patients without EHF but with an identified sepsis (sepsis
      group). The serum levels of interleukin (IL)-1beta, tumor necrosis factor-alpha
      (TNF-alpha), IL-6, and IL-8 were compared among the three groups. RESULTS: In the
      EHF group, the levels of each cytokine peaked at day 1 postoperatively. Cytokine
      levels at day 1 were significantly higher in the EHF group than in the control
      group (p<0.0006) or in the sepsis group (p<0.003 except for TNF-alpha).
      CONCLUSION: We conclude that EHF is associated with a massive release of
      proinflammatory cytokines that could play a determinant role in the pathogenesis
      of this complication.

PMID- 9515838
TI  - Rate of FEV1 change following lung volume reduction surgery.
AB  - INTRODUCTION: Lung volume reduction surgery (LVRS) improves pulmonary function
      and dyspnea symptoms acutely in selected patients with heterogeneous emphysema.
      Limited data are available regarding long-term function following LVRS. We
      analyzed short-term (<6 months) and long-term rate of change of pulmonary
      function in 376 patients who underwent unilateral or bilateral LVRS using
      thoracoscopic or median sternotomy, staple, laser, or combined techniques. We
      hypothesized that the long-term rate of deterioration in lung function would be
      dependent on the surgical procedure used and would be greatest in those with the
      largest short-term postoperative improvement. METHODS: Pulmonary function was
      assessed preoperatively and at repeated intervals following LVRS. The change in
      pulmonary function over time was assessed for each patient by determining the
      individual change in FEV1 using linear regression analysis short and long term.
      Overall rate of change in pulmonary function was calculated for the composite
      group of patients and subgrouped by operative procedure. RESULTS: Lung function
      appears to improve in the first few months following LVRS in most patients,
      maximizing at approximately 3 to 6 months and declining thereafter. The short
      term incremental improvement following staple procedures is superior to
      improvements following laser procedures or unilateral surgery: FEV1 increase
      (mean+/-SD) of 0.39+/-0.03 L for bilateral staple, 0.25+/-0.03 L for unilateral
      staple, 0.10+/-0.03 L for unilateral laser, and 0.22+/-0.1 L for mixed unilateral
      staple/laser procedures. However, the long-term rate of decline in FEV1 was
      greatest for bilateral staple LVRS procedures as well: 0.255+/-0.057 L/yr for
      bilateral staple, 0.107+/-0.068 L/yr for unilateral staple, 0.074+/-0.034 L/yr
      for unilateral laser, and 0.209+/-0.12 L/yr for mixed staple laser procedures.
      There was a general correlation between the magnitude of short-term incremental
      improvement and the rate of deterioration in FEV1 (r=0.292, p=0.003).
      CONCLUSIONS: While bilateral staple LVRS procedures lead to greater short-term
      improvement in FEV1, the more rapid rate of FEV1 decline in these patients and
      the general association between greater short-term incremental improvement and
      higher rates of deterioration raise questions regarding optimal long-term
      procedures. Further studies will be needed to answer these important questions.

PMID- 9515839
TI  - Pathologic findings in lung volume reduction surgery.
AB  - PURPOSE: Lung volume reduction surgery (LVRS) has re-emerged as an alternative in
      the management of patients with chronic, debilitating, emphysematous lung
      disease. This has permitted the formal evaluation of pathologic pulmonary changes
      present in these patients. This study seeks to describe systematically the
      pathologic findings present in patients undergoing LVRS. METHODS: Tissue sections
      stained with hematoxylin-eosin, as well as special stains, were retrospectively
      reviewed from the specimens of 65 nonconsecutive LVRS patients (male patients,
      66%; female patients, 31%; mean age, 63.2+/-6.76 yr). All operations were
      conducted via an open technique (bilateral, 83%; unilateral, 17%). RESULTS:
      Histologic emphysema grade was mild in 9%, moderate in 72%, and severe in 19% of
      patients. Microscopic bullae were noted in 75% of specimens. Three patients, each
      with radiographic evidence of a lesion preoperatively, had small (1.1 to 2.8 cm)
      adenocarcinomas. Granulomatous bronchiolitis and pneumonitis were noted in one
      patient who postoperatively developed progressive respiratory compromise. An old,
      inactive aspergilloma was found in the specimen of another patient. Additional
      findings of potential clinical significance included bronchiolitis (54),
      bronchiolectasis (6), and bronchoalveolar metaplasia (1). Incidental findings
      included interstitial fibrosis and scar (55), interstitial inflammation (20),
      calcification (20), and ossification (11), bone marrow emboli (4), chemodectoma
      (2), and carcinoid tumorlets (1). CONCLUSION: This systematic analysis of the
      resected specimens from patients undergoing LVRS describes a wide range of
      pathologic findings, including those clinically relevant, as well as incidental.
      As the application of LVRS continues to expand, the likelihood of discovering
      clinically significant pathologic lesions (eg, carcinoma) will undoubtedly
      increase.

PMID- 9515840
TI  - Association between right ventricular function and perfusion abnormalities in
      hemodynamically stable patients with acute pulmonary embolism.
AB  - BACKGROUND/OBJECTIVES: Patients presenting with acute pulmonary embolism
      associated with hemodynamic compromise exhibit right ventricular enlargement and
      dysfunction on transthoracic echocardiogram. However, the degree of
      echocardiographic abnormalities among hemodynamically stable patients without
      preexisting cardiopulmonary disease during the acute stage of pulmonary embolism,
      and following treatment, is unknown. Therefore, this study was designed to assess
      the extent of right ventricular abnormalities detected on transthoracic
      echocardiogram in patients following acute pulmonary embolism and during
      treatment with anticoagulation or vena caval interruption. The extent of
      pulmonary vascular obstruction and complication rate on follow-up were also
      assessed. DESIGN/INTERVENTIONS: Sixty-four consecutive hemodynamically stable
      patients without preexisting known cardiopulmonary disorder presenting with acute
      pulmonary embolism and undergoing treatment with anticoagulation or inferior vena
      caval interruption were studied. All subjects underwent a two-dimensional
      transthoracic echocardiogram within 24 h of diagnosis. The degree of perfusion
      abnormality on lung scan was quantified. Twenty-six patients underwent follow-up
      echocardiogram and lung scan at 6 weeks. The echocardiographic findings were
      compared with those obtained from a group of normal control subjects matched for
      gender and age. RESULTS: Although the mean right ventricular end-diastolic areas
      did not differ (21.9+/-5.2 cm2 vs 20.1+/-2.9 cm2 for control subjects; p=not
      significant), the right ventricular end-systolic area was larger in comparison to
      our series of control subjects (14.6+/-5.1 cm2 vs 11.7+/-2.0 cm2; p=0.025).
      Fractional right ventricular area change was reduced in the patient group
      compared with the control subjects (34.3+/-9.0% vs 41.3+/-7.0%; p=0.003). The
      extent of right ventricular end-systolic area enlargement and decrease in
      fractional area change did not correlate with the degree of pulmonary vascular
      obstruction. Patients who were restudied at 6 weeks showed minimal improvement in
      echocardiographic findings, despite almost complete resolution of perfusion
      defects on lung scan. CONCLUSIONS: The extent of right ventricular dysfunction in
      hemodynamically stable, previously normal patients with acute pulmonary embolism
      does not reflect the extent of the perfusion abnormalities. Further, right
      ventricular enlargement and systolic dysfunction are present and persistent
      despite treatment with heparin and warfarin therapy or vena caval interruption.

PMID- 9515841
TI  - Use of transesophageal echocardiography to predict significant coronary artery
      disease in aortic stenosis.
AB  - STUDY OBJECTIVES: This study was conducted to examine if the use of multiplane
      transesophageal echocardiography (TEE) could predict the absence or the presence
      of significant coronary artery disease (CAD) in patients with aortic stenosis.
      DESIGN: Prospective study. SETTING: University hospital. PATIENTS: Clinical,
      angiographic features and TEE findings were prospectively analyzed in 132
      consecutive patients with aortic stenosis. MEASUREMENTS AND RESULTS: In 63
      patients with significant CAD, 57 had thoracic aortic plaque on TEE studies. In
      contrast, aortic plaque existed in only 19 of the remaining 69 patients with
      normal or mildly abnormal coronary arteries. Therefore, the presence of aortic
      plaque on the TEE identified significant CAD with a sensitivity of 90.5%, a
      specificity of 72.5%, and with positive and negative predictive values of 75.0%
      and 89.3%, respectively. There was a significant relation between the severity of
      thoracic aortic atherosclerosis and the severity of CAD (p<0.0001). Multivariate
      logistic regression analysis revealed that aortic plaque, angina, and age were
      independent predictors of CAD. Aortic plaque was the most significant independent
      predictor. CONCLUSION: This prospective study indicates that TEE examination of
      thoracic atherosclerotic plaque is a powerful predictor of absence of significant
      CAD in patients with aortic stenosis.

PMID- 9515842
TI  - Coronary bypass grafting for single-vessel coronary artery disease: a 17-year
      review with short- and long-term follow-up.
AB  - STUDY OBJECTIVES: We reviewed our short- (30 days) and long-term (up to 17 years)
      experience with surgical revascularization for patients with angiographically
      documented isolated single-vessel coronary artery disease. DESIGN: Retrospective
      study of single-vessel coronary artery bypass procedures performed from January
      1980 through June 1996. During this time, 100 consecutive patients underwent a
      single-vessel coronary artery bypass. All patients were men with a mean age of
      59+/-9 years (range, 35 to 78 years) and a mean ejection fraction of 56+/-8%
      (range, 35 to 77%). The vessels bypassed included the left anterior descending in
      66 (66%), right coronary artery in 31 (31%), and the obtuse marginal in 3 (3%).
      RESULTS: Short-term results reveal no deaths and six (6.0%) complications. Long
      term follow-up by chart review and telephone survey was available in 87 (87%)
      patients at a mean of 46.9 months (range, 12 to 151 months). Cumulative freedom
      from angina and repeated revascularization was 93% and 98% at 1 year and 55% and
      81% at 10 years, respectively (Kaplan-Meier). CONCLUSION: Single-vessel coronary
      artery bypass for isolated single-vessel disease can be performed with minimal
      morbidity and no mortality and provides excellent long-term relief of angina.

PMID- 9515843
TI  - The influence of perioperative myocardial infarction on long-term prognosis
      following elective vascular surgery.
AB  - STUDY OBJECTIVE: The present study was performed to determine the influence of a
      perioperative myocardial infarction on long-term mortality in patients who have
      undergone elective vascular surgery. STUDY DESIGN: This was a 4-year follow-up of
      patients who had undergone elective vascular procedures at a Veterans Affairs
      Medical Center. Between January 1989 and December 1990, 115 consecutive patients
      underwent surgery for either an expanding abdominal aortic aneurysm (AAA) (38%)
      or for pain in the lower extremities (62%). RESULTS: Vital status at 4 years
      postsurgery was determined for all patients. Thirty-day postoperative mortality
      was 3%, while estimates at 1, 2, 3, and 4 years were 19%, 26%, 35%, and 39%,
      respectively. Of the 45 patients who died within 4 years following surgery, the
      major causes of death were cardiac (40%), cancer (18%), cerebrovascular (13%),
      and peripheral vascular disease (11%). Univariate predictors of 1-year mortality
      on preoperative evaluation were an abnormal ECG, moderate or greater sized
      exercise thallium defect and left ventricular ejection fraction < or =40%, and a
      perioperative myocardial infarction. Univariate predictors of 4-year mortality
      were non-AAA surgery and diabetes mellitus. Perioperative myocardial infarction
      was a marginally significant independent predictor of 1-year mortality (p=0.06),
      while the need for non-AAA surgery was a strong independent predictor at 4 years.
      CONCLUSIONS: Cardiac mortality is the major cause of late death among patients
      undergoing elective vascular surgery. Although preoperative indicators of
      symptomatic coronary artery disease and nonfatal perioperative myocardial
      infarction identified those individuals at increased mortality in the first
      postoperative year, the extent of vascular disease at presentation may be a more
      important determinant of long-term survival. A randomized trial in such patients
      is needed to assess the best strategy for treating patients with coexistent
      coronary artery and vascular diseases.

PMID- 9515844
TI  - Preoperative bronchoscopic assessment of airway invasion by esophageal cancer: a
      prospective study.
AB  - BACKGROUND: Bronchoscopy is frequently used to assess invasion of esophageal
      cancer into the tracheobronchial tree. Prospective studies evaluating the role of
      bronchoscopy in pretherapeutic staging of esophageal cancer are lacking. STUDY
      OBJECTIVES: To evaluate the diagnostic utility of fiberoptic bronchoscopy for the
      assessment of airway involvement by esophageal carcinoma and its resectability.
      PATIENTS AND METHODS: In a prospective study, we analyzed 150 bronchoscopies in
      116 consecutive patients with potentially operable esophageal carcinoma, and
      correlated the findings with other staging modalities, intraoperative evaluation,
      and histopathologic data. RESULTS: One unknown additional bronchial cancer was
      found. In 32% of bronchoscopies performed in patients with esophageal cancer
      located above the tracheal bifurcation, some macroscopic abnormality was detected
      in the trachea and main bronchi, with mobile protrusion of the posterior tracheal
      wall being the most frequent abnormality (20.7%). When compared with histologic
      results, normal macroscopic appearance of the trachea and main bronchi had a
      negative predictive value of 98.5%, but the positive predictive value of all
      macroscopic abnormalities for the diagnosis of airway involvement was low,
      particularly after radiation therapy. The overall accuracy of bronchoscopy with
      multiple brush cytology and biopsy sampling in proving or excluding airway
      invasion in patients with otherwise operable conditions was 95.8% (95% confidence
      interval, 88.3 to 99.1%). Bronchoscopy was the sole decisive staging procedure,
      resulting in exclusion from surgery because of airway invasion, in 9.7% of
      patients with otherwise potentially operable conditions. The results of
      bronchoscopy and CT were discordant in 40% of the patients; the specificity and
      positive predictive value were higher for bronchoscopy than for CT. CONCLUSIONS:
      When performed as the last investigation in the staging workup, bronchoscopy with
      biopsy and brush cytology is a very accurate procedure in evaluating possible
      airway invasion of esophageal cancer; macroscopic findings alone are not
      reliable.

PMID- 9515845
TI  - Localization of bronchial intraepithelial neoplastic lesions by fluorescence
      bronchoscopy.
AB  - BACKGROUND: In the treatment of lung cancer, the best outcome is achieved when
      the lesion is discovered in the intraepithelial (preinvasive) stage. However,
      intraepithelial neoplastic lesions are difficult to localize by conventional
      white-light bronchoscopy (WLB). OBJECTIVE: To determine if autofluorescence
      bronchoscopy, when used as an adjunct to WLB, could improve the bronchoscopist's
      ability to locate and remove biopsy specimens from areas suspicious of
      intraepithelial neoplasia as compared with WLB alone. METHOD: A multicenter
      clinical trial was conducted in seven institutions in the United States and
      Canada. WLB followed by fluorescence examination with the light-induced
      fluorescence endoscopy (LIFE) device was performed in 173 subjects known or
      suspected to have lung cancer. Biopsy specimens were taken from all areas
      suspicious of moderate dysplasia or worse on WLB and/or LIFE examination. In
      addition, random biopsy specimens were also taken from other parts of the
      bronchial tree. RESULTS: The relative sensitivity of WLB + LIFE vs WLB alone was
      6.3 for intraepithelial neoplastic lesions and 2.71 when invasive carcinomas were
      also included. The positive predictive value was 0.33 and 0.39 and the negative
      predictive value was 0.89 and 0.83, respectively, for WLB+LIFE and WLB alone.
      CONCLUSION: Autofluorescence bronchoscopy, when used as an adjunct to standard
      WLB, enhances the bronchoscopist's ability to localize small neoplastic lesions,
      especially intraepithelial lesions that may have significant implication in the
      management of lung cancer in the future.

PMID- 9515846
TI  - Importance of intrapulmonary lymph nodes in the differential diagnosis of small
      pulmonary nodular shadows.
AB  - STUDY OBJECTIVE: The objectives of the present study were to evaluate the
      importance of intrapulmonary lymph nodes (IPLNs) in the differential diagnosis of
      small pulmonary nodules and to review the CT findings of IPLNs. DESIGN:
      Retrospective analysis of patient records. SETTING: Chest Disease Research
      Institute Hospital, Kyoto University. PATIENTS: Between January 1991 and May
      1996, we examined 26 patients with pulmonary nodular shadows smaller than 1 cm in
      diameter that could not be diagnosed before surgery. All patients (19 men, 7
      women) underwent chest CT (28 to 72 years old; mean, 52.3 years). RESULTS: The
      pathologic diagnoses were IPLNs in 46.2% (12/26), pulmonary hamartoma in 23.1%
      (6/26), lung cancer in 11.5% (3/26), pulmonary tuberculoma in 11.5% (3/26), and
      metastatic lung tumor in 7.7% (2/26). IPLNs were located in the lower lobe in
      72%. The characteristic CT findings of IPLNs were a clear border and location
      close to the pleura. Two of them resembled lung cancer. The CT features in these
      two IPLNs and in three small lung cancers overlapped. CONCLUSIONS: In the present
      study, we investigated small nodular shadows <1 cm in diameter and found that
      IPLNs located underneath the pleura are important to consider in the differential
      diagnosis of lung cancer. The CT scan findings of IPLNs were not necessarily
      specific and sometimes resembled those of lung cancer. Because of their location,
      video-assisted thoracic surgery is useful in making a definite diagnosis.

PMID- 9515847
TI  - The effect of a mandibular advancement device on apneas and sleep in patients
      with obstructive sleep apnea.
AB  - OBJECTIVE: To evaluate the effects of a mandibular advancement device on apneas
      and sleep in mild, moderate, and severe obstructive sleep apnea. DESIGN:
      Prospective study. SUBJECTS: Forty-four of 47 patients included. INTERVENTION:
      Individually adjusted mandibular advancement devices. MEASUREMENTS:
      Polysomnographic sleep recordings for 1 night without the device and 1 night with
      it, with a median of 1 day and no changes in weight, medication, or sleep
      position between the recordings. RESULTS: The device reduced the median
      obstructive apnea-hypopnea index from 11 (range, 7 to 19) to 5 (range, 0 to 17)
      (p<0.001) in 21 patients with mild sleep apnea, from 27 (range, 20 to 38) to 7
      (range, 1 to 19) (p<0.001) in 15 patients with moderate sleep apnea, and from 53
      (range, 44 to 66) to 14 (range, 2 to 32) (p<0.05) in 8 patients with severe sleep
      apnea. The arousal index decreased and the sleep stage patterns improved in all
      severity groups. Twenty-eight of 44 patients were successfully treated with an
      obstructive apnea-hypopnea index of below 10 and a subjective reduction in
      snoring. Nine of 16 patients with treatment failure still reported a reduction in
      snoring. The success rate correlated inversely to the disease severity (r=-0.41;
      p<0.01). CONCLUSIONS: A mandibular advancement device reduces apneas and improves
      sleep quality in patients with obstructive sleep apnea, especially in those with
      mild and moderate disease. A follow-up sleep recording during treatment is
      necessary because of the risk of silent obstructive apneas without subjective
      snoring with the device.

PMID- 9515848
TI  - Use of conventional and self-adjusting nasal continuous positive airway pressure
      for treatment of severe obstructive sleep apnea syndrome: a comparative study.
AB  - STUDY OBJECTIVES: To compare conventional and self-adjusting nasal continuous
      positive airway pressure (nCPAP) therapy in patients with severe obstructive
      sleep apnea syndrome with respect to suppression of respiratory disturbances,
      quality of sleep, mean mask pressure, and patient compliance. DESIGN: Cohort
      study of consecutive patients with obstructive sleep apnea syndrome, single
      blinded. SETTING: Clinical sleep laboratory in Germany. PATIENTS: Fifty patients
      (44 men, 6 women who ranged in age from 35 to 71 years) with polysomnographically
      confirmed severe obstructive sleep apnea syndrome (respiratory disturbance index
      [RDI], >20/h). MEASUREMENTS AND INTERVENTIONS: After baseline polysomnography,
      patients were randomly treated with nCPAP either in conventional (group 1) or in
      automatically adjusting (group 2) mode. Three to 6 months after adjustment, all
      patients underwent polysomnography again. They also were examined with a portable
      monitoring device and received a questionnaire on subjective well-being and
      device evaluation. RESULTS: Anthropometric and respiratory data were comparable
      in both groups; body mass index had not changed significantly in the follow-up.
      RDI dropped by 91.5% (from 38.3+/- 13.9/h to 3.6+/-4.4/h) in conventional and by
      93.6% (from 35.5+/-9.6/h to 2.4+/-1.6/h) in self-adjusting mode (statistically
      not significant [NS]). Sleep efficiency decreased by 4.0% in conventional and
      increased by 2.0% in self-adjusting mode (NS). In both groups, normal sleep
      structure was largely restored. Mean mask pressure was 8.1+/-2.5 cm H2O in group
      1 and 6.5+/-1.7 cm H2O in group 2 (p<0.01). Patient compliance in terms of nights
      per week of mask appliance was better in the self-adjusting mode (5.7+/-0.7 to
      6.5+/-0.4; p<0.01). CONCLUSION: Self-adjusting nCPAP demonstrates the same
      reliability in suppression of respiratory disturbances as fixed-mask pressure
      therapy. Sleep quality is slightly superior, patient compliance is highly
      significantly better.

PMID- 9515849
TI  - Hour-to-hour variability of oxygen saturation in sleep apnea.
AB  - STUDY OBJECTIVES: Methods used to express the severity of oxygen desaturation
      during polysomnography include the average oxygen saturation (AO2), lowest oxygen
      saturation (LO2), and the percent of the total time with oxygen saturation level
      lower than 90% (T<90%). We wanted to determine which one of these methods is
      least variable during different hours of monitoring. DESIGN: Prospective,
      observational study. SETTING: Sleep center at a medical university. PATIENTS: One
      hundred fifty patients with apnea-hypopnea index from 5 to 130. MEASUREMENTS:
      AO2, LO2, and T<90% were calculated during each of the 8 h of polysomnography.
      Data for each hour were compared and the Cronbach alpha coefficients were
      calculated. RESULTS: There was a high degree of correlation among the three
      methods as well as between each method and the severity of sleep apnea. The
      mean+/-SD values for each method were as follows: AO2, 92.7+/-5.6; LO2, 68.5+/
      19.3; and T<90%, 15.7+/-24.2. The alpha coefficients for these methods were AO2,
      0.98; LO2, 0.88; and T<90%, 0.98. In all methods, the data of the first hour were
      significantly different from the data of the subsequent hours. CONCLUSION: Both
      AO2 and T<90% methods show less hour to hour variability compared with LO2, and
      there is more variability in the first hour. Since the AO2 values >90% may not
      convey the severity of O2 desaturation, T<90% may be the best method of
      expressing oxygen saturation changes during polysomnography.

PMID- 9515850
TI  - Factors predictive of survival among 337 patients with mesothelioma treated
      between 1984 and 1994 by the Cancer and Leukemia Group B.
AB  - PURPOSE: To examine the individual and joint effect of various pretreatment
      clinical characteristics on the survival of patients with mesothelioma treated by
      the Cancer and Leukemia Group B (CALGB). PATIENTS AND METHODS: Between June 1984
      and September 1994, 337 patients with malignant mesothelioma and no prior
      chemotherapy were accrued to seven phase II studies conducted by the CALGB which
      screened the efficacy of 10 treatment regimens or dose levels. The eligibility
      criteria for all studies were virtually identical. Patient characteristics
      include the following: age older than 60 years (63%); male (83%); performance
      status (PS) of 0 or 1 (81%); chest pain (60%); definite asbestos exposure (62%);
      >5% weight loss (41%); and pleural involvement (94%). Median survival time (MST)
      for the 10 treatment regimens ranged from 3.9 to 9.8 months (overall=7.2; 95%
      confidence interval [CI], 6.5 to 8.3), with 1-year survival between 14% and 50%
      (overall=27%; 95% CI, 23 to 33%). RESULTS: Cox survival models and exponential
      regression trees were used to examine the prognostic importance of pretreatment
      patient characteristics. Univariate analyses show that patients with poor Eastern
      Cooperative Oncology Group PS, chest pain, dyspnea, platelet count (PLT)
      >400,000/microL, weight loss, serum lactate dehydrogenase (LDH) level >500 IU/L,
      pleural involvement, low hemoglobin (HGB) level, high WBC count, and increasing
      age over 75 years have a worse prognosis. With decreasing risk ratio,
      multivariate Cox analyses showed that pleural involvement, LDH >500 IU/L, poor
      PS, chest pain, PLT >400,000/microL, nonepithelial histology, and increasing age
      older than 75 years jointly predict poor survival. PS was the most important
      prognostic split in the regression tree. Terminal nodes were amalgamated to form
      six distinct prognostic subgroups with MST (2-year survival) of 13.9 (38%) in 36
      patients, 9.5 (21%) in 36 patients, 9.2 (10%) in 146 patients, 6.5 (3%) in 33
      patients, 4.4 (0%) in 73 patients, and 1.4 (0%) in 13 patients (p<0.0001).
      CONCLUSIONS: The subgroup with the best survival (MST=13.9 months) included
      patients with PS=0 and age younger than 49 years, and patients with PS=0, age of
      49 years or older, and HGB > or =14.6. The worst survival (MST= 1.4 months)
      occurred for patients with PS= 1/2 and WBC > or =15.6/microL.

PMID- 9515851
TI  - Video-assisted talc pleurodesis for malignant pleural effusions utilizing local
      anesthesia and I.V. sedation.
AB  - METHODS: Twenty-four consecutive patients aged 36 to 84 years (mean, 63.3+/-12.9
      years) underwent video-assisted talc pleurodesis (VATP) for malignant pleural
      effusion (MPE) utilizing local anesthesia with IV sedation at the Walter Reed
      Army Medical Center. The VATP procedure was performed in the operating room with
      the patient in the lateral decubitus position breathing spontaneously through a
      face mask with 4 L/min of oxygen. Anesthesia was achieved by intercostal nerve
      block using a 50/50 mixture of 1% lidocaine with epinephrine and 0.5% bupivacaine
      hydrochloride (Marcaine) supplemented with local infiltration of the access
      (Surgiport) sites as necessary. Sedation was achieved with propofol, and
      pleurodesis was performed with 3 to 8 g (average, 5 g) of sterile talc
      insufflated through a talc atomizer. RESULTS: The mean operating time was 44.3+/
      14.9 min (range, 23 to 75 min). The average number of days of chest tube drainage
      was 2.9+/-1.2 days (range, 1 to 5 days). Patients stayed on the cardiothoracic
      ward for an average of 4.4+/-1.3 days before discharge home or transfer to a
      medical oncology ward. Seventeen of the 24 patients (71%) had excellent results,
      4 patients (17%) had good results, and 3 patients (12%) had poor results. The
      three patients with poor results all had primary lung cancer as their underlying
      malignancy. The overall actuarial survival was 66% at 6 months, 48% at 12 months,
      and 32% at 24 months with a mean survival of 9 months. There was one operative
      death in an 84-year-old patient with primary lung cancer. Twelve of the 24
      patients are alive 4 to 30 months after VATP. CONCLUSIONS: VATP, performed under
      local anesthesia, is a safe and highly effective method of managing MPE.

PMID- 9515852
TI  - Emergency department cardiopulmonary bypass in the treatment of human cardiac
      arrest.
AB  - OBJECTIVE: To study the use of emergency department (ED) femoro-femoral
      cardiopulmonary bypass (CPB) in the resuscitation of medical cardiac arrest
      patients. DESIGN: Prospective, uncontrolled trial. SETTING: Urban academic ED
      staffed with board-certified emergency physicians (EPs). PARTICIPANTS: Ten
      patients with medical cardiac arrest unresponsive to standard therapy.
      INTERVENTIONS: Femoro-femoral CPB instituted by EPs. RESULTS: The time of cardiac
      arrest prior to CPB (mean+/-SD) was 32.0+/-13.6 min. The cardiac output while on
      CPB was 4.09+/-1.03 L/min with an average of 229+/-111 min on bypass. All 10
      patients had resumption of spontaneous cardiac activity while on CPB. Seven of
      these were weaned from CPB with intrinsic spontaneous circulation. Of these, six
      patients were transferred from the ED to the operating room for cannula removal
      and vessel repair while the other patient died in the ED soon after discontinuing
      CPB. Mean survival was 47.8+/-44.7 h in the six patients leaving the ED. Although
      these patients had successful hemodynamic resuscitation, there were no long-term
      survivors. CONCLUSION: CPB instituted by EPs is feasible and effective for the
      hemodynamic resuscitation of cardiac arrest patients unresponsive to advanced
      cardiac life support therapy. Future efforts need to focus on improving long-term
      outcome.

PMID- 9515853
TI  - Nursing staff in intensive care in Europe: the mismatch between planning and
      practice.
AB  - OBJECTIVE: To test the use of a human resources-based classification of levels of
      care of ICUs; to evaluate the match between planned vs operative levels of care
      on a large sample of European ICUs. DESIGN: Analysis of the database of a
      multicentric, multinational, prospective cohort study, involving 89 ICUs from 13
      European areas. SETTING: Database of EURICUS-I. METHODS: Provision of resources
      was measured as the number of nurses per ICU bed. Use of resources was measured
      by the daily use of a therapeutic index (nine equivalents of nursing manpower use
      score, NEMS) at patient level. Work utilization ratio (WUR) indicated the total
      number of NEMS points actually scored divided by the total possible NEMS score on
      each ICU. The planned level of care (LOC) or the mean number of patients to be
      assisted by one nurse (P/N ratio) made available to the unit was derived from the
      number of nurses and the number of beds in the ICU. The operative LOC or the
      actual mean number of patients who were assisted by one nurse (P/N ratio) was
      computed by dividing the number of NEMS points equivalent to the work of three
      nursing-shifts (46 points) by the mean daily NEMS score at ICU level. Severity of
      illness was evaluated by the new simplified acute physiology score. Kappa
      statistics, intraclass correlation coefficients, and interrater percentage of
      agreement were used to evaluate the reliability of the data collected for total
      NEMS score. Chi2 statistics and one-way analysis of variance were used when
      appropriate. MAIN RESULTS: Data of 16,047 patients (74,383 patient-days) admitted
      to the ICUs were analyzed. With an overall value of 26.5+/-9.3, the mean NEMS
      score at ICU level varied significantly among European areas. These differences
      were not explained by the severity of illness of the patients. The mean WUR was
      0.73+/-0.29, presenting also significant differences among ICUs and European
      areas that were not explained by severity of illness. There was a mismatch
      between planned vs operative LOCs on 68 ICUs (76%); on 65 (73%), the operative
      LOC was lower than the planned LOC. This loss of resources concerned particularly
      the 61 ICUs planned to operate at LOC 3. CONCLUSIONS: The use of human resources
      based classification of LOCs is an objective method for evaluation of the match
      between provision and use of resources in the ICU. This study has shown a large
      mismatch between planned and utilized LOC in a sample of 89 European ICUs. This
      mismatch, suggesting an important loss of invested resources, was more apparent
      in the ICUs that were planned to operate at a higher level of care.

PMID- 9515854
TI  - A randomized clinical trial comparing an extended-use hygroscopic condenser
      humidifier with heated-water humidification in mechanically ventilated patients.
AB  - STUDY OBJECTIVE: To determine the safety and cost-effectiveness of mechanical
      ventilation with an extended-use hygroscopic condenser humidifier (Duration;
      Nellcor Puritan-Bennett; Eden Prairie, Minn) compared with mechanical ventilation
      with heated-water humidification. DESIGN: Prospective randomized clinical trial.
      SETTING: Medical and surgical ICUs of Barnes-Jewish Hospital, St. Louis, a
      university-affiliated teaching hospital. PATIENTS: Three hundred ten consecutive
      qualified patients undergoing mechanical ventilation. INTERVENTIONS: Patients
      requiring mechanical ventilation were randomly assigned to receive humidification
      with either an extended-use hygroscopic condenser humidifier (for up to the first
      7 days of mechanical ventilation) or heated-water humidification. MEASUREMENTS:
      Occurrence of ventilator-associated pneumonia, endotracheal tube occlusion,
      duration of mechanical ventilation, lengths of intensive care and
      hospitalization, acquired multiorgan dysfunction, and hospital mortality.
      RESULTS: One hundred sixty-three patients were randomly assigned to receive
      humidification with an extended-use hygroscopic condenser humidifier, and 147
      patients were randomly assigned to receive heated-water humidification. The two
      groups were similar at the time of randomization with regard to demographic
      characteristics, ICU admission diagnoses, and severity of illness. Risk factors
      for the development of ventilator-associated pneumonia were also similar during
      the study period for both treatment groups. Ventilator-associated pneumonia was
      seen in 15 (9.2%) patients receiving humidification with an extended-use
      hygroscopic condenser humidifier and in 15 (10.2%) patients receiving heated
      water humidification (relative risk, 0.90; 95% confidence interval=0.46 to 1.78;
      p=0.766). No statistically significant differences for hospital mortality,
      duration of mechanical ventilation, lengths of stay in the hospital ICU, or
      acquired organ system derangements were found between the two treatment groups.
      No episode of endotracheal tube occlusion occurred during the study period in
      either treatment group. The total cost of providing humidification was $2,605 for
      patients receiving a hygroscopic condenser humidifier compared with $5,625 for
      patients receiving heated-water humidification. CONCLUSION: Our findings suggest
      that the initial application of an extended-use hygroscopic condenser humidifier
      is a safe and more cost-effective method of providing humidification to patients
      requiring mechanical ventilation compared with heated-water humidification.

PMID- 9515855
TI  - Transcutaneous PCO2 to monitor noninvasive mechanical ventilation in adults:
      assessment of a new transcutaneous PCO2 device.
AB  - The present study was designed to analyze the usability of a commercially
      available, transcutaneous PCO2 (TcPCO2) sensor for monitoring noninvasive
      positive pressure ventilation (NPPV). Twenty-six hemodynamically stable patients
      with intra-arterial radial catheters were assessed. After stabilization of
      TcPCO2, arterial blood was analyzed and results were compared with TcPCO2 at time
      of sampling. To evaluate the drift of the signal, samples were taken hourly in
      five patients for 4 h while continuously recording TcPCO2. Finally, to assess for
      the response of the sensor to changes in PaCO2, six patients underwent continuous
      TcPCO2 recording while initiating or interrupting NPPV; arterial samples were
      analyzed before the event, and 1, 3, 5, 7, 9, and 20 min afterwards. RESULTS:
      TcPCO2 and PaCO2 were tested over a range of 26 to 71 mm Hg, and were found to be
      closely correlated (r=0.968, p<0.0001); mean bias was 0.75 mm Hg. There was no
      significant drift of TcPCO2 as compared with PaCO2 over 4 h. The time of response
      of TcPCO2 to initiation or interruption of NPPV was <60 s. An estimation of the
      lag time averaged 5+/-3 min (range, 1 to 9 min). CONCLUSION: TcPCO2 in
      hemodynamically stable adults was in excellent agreement with arterial
      measurements. The time of response to a change in ventilation was compatible with
      the aim of clinical monitoring of patients under NPPV.

PMID- 9515856
TI  - The effect of physiologic and mechanical aging on the performance of peak
      flowmeters.
AB  - PURPOSE: To investigate the effects of physiologic and mechanical aging on peak
      flowmeters. MATERIALS AND METHODS: Eight each of MiniWright (MW; Clement Clark;
      Harlow, UK), Personal-Best (PB; HealthScan Products; Cedar Grove, NJ),
      Vitalograph (V; Vitalograph Ltd; Buckingham, UK), and Breath-Taker (BT; Medical
      Development Australia; Melbourne, Australia) peak flowmeters were assessed for
      accuracy and repeatability before and after aging using a computer-driven syringe
      to deliver peak flows from 100 to 700 L/min. Four of each type of flowmeter were
      physiologically aged by normal subjects performing up to six peak flows daily for
      1 year. The remaining four of each flowmeter were mechanically aged using an
      accelerated aging device to deliver 2,000 exponential waveforms with a peak flow
      of 600 L/min over a period of 3 h. RESULTS: The V and BT flowmeters were linear
      and accurate over the range 100 to 700 L/min, while the PB overread at high
      flows. The MW was alinear throughout. The SD of the difference between readings
      before and after aging ranged from 8.6 to 40.6 L/min (mean, 9.2). Comparing the
      slopes of the relationship of actual against reference peak expiratory flow (PEF)
      showed that 16 flowmeters--5 BTs, 6 MWs, 4 PBs, and 1 V had no significant change
      in slope after aging. Mechanical aging caused a consistent underreading in PEF at
      high flow rates. Physiologic aging showed a more variable pattern both within and
      between flowmeter types. The MW was the most affected by physiologic aging,
      producing overestimates of PEF by as much as 100 L/min at 500 L/min. CONCLUSIONS:
      We conclude that the effects of physiologic and mechanical aging are different,
      and that while mechanical aging may provide a guide to the effects of aging,
      studies using physiologic aging would be more appropriate.

PMID- 9515857
TI  - Patterns of dissimilarities among instrument models in measuring PO2, PCO2, and
      pH in blood gas laboratories.
AB  - STUDY OBJECTIVES: To ascertain the degree of dissimilarities among blood gas and
      pH analyzer models of the same and different manufacturers in measurement of PO2,
      PCO2, and pH using fluorocarbon containing emulsion (FCE) proficiency testing
      material. DESIGN: Statistically and graphically analyze data from six recent
      proficiency testing surveys for the 20 more frequently used models of analyzers.
      SETTING AND PARTICIPANTS: Over a 2-year period, approximately 900 participants
      from blood gas laboratories in the United States analyzed similar ampules from
      each of 30 lots. MEASUREMENTS AND RESULTS: Both graphic and statistical
      comparisons were used to demonstrate differences between manufacturers. For each
      of the four major manufacturers, comparisons revealed statistically significant
      differences not only for PO2, but also for PCO2 and pH. Additionally, comparison
      models within each of the three manufacturers (those with multiple models and >
      15 instruments per model represented) disclosed statistically significant
      dissimilarities among models for each analyte in 115 of 153 model pairings.
      Previously reported tonometered blood differences among analyzer models for PO2
      are qualitatively similar to the differences found in these same models in this
      FCE study. Model differences are important in research studies and may be
      clinically important in deciding abnormality, selecting oxygen therapy, or the
      treatment of patients with respiratory failure or severe respiratory alkalosis.
      CONCLUSIONS: To minimize the likelihood of misleading clinicians, laboratory
      directors should consider the degree of dissimilarity among blood gas analyzer
      models in current use and when changing instrumentation.

PMID- 9515858
TI  - Elevated pleural fluid levels of defensins in patients with empyema.
AB  - BACKGROUND: Defensins, also known as human neutrophil peptides, are antimicrobial
      peptides present in the azurophil granules of neutrophils. We measured their
      level in pleural effusion in various pulmonary diseases to investigate whether
      they could be used as a diagnostic marker in the differential diagnosis of
      specific pleural diseases. PATIENTS AND PARTICIPANTS: We analyzed pleural
      effusion samples collected from 61 patients, including 50 exudates (11 with
      empyema, 3 parapneumonic, 15 tuberculous, 18 neoplastic, 3 miscellaneous) and 11
      transudates as controls. MEASUREMENTS: Defensins were measured by
      radioimmunoassay and also analyzed by reverse-phase high-performance liquid
      chromatography. The concentrations of interleukin (IL)-8 and granulocyte colony
      stimulating factor (G-CSF) in pleural effusion fluid were measured by enzyme
      linked immunosorbent assay to examine the correlation between these cytokines and
      defensins. RESULTS: The concentration of defensins in all samples of empyema was
      >5,100 ng/mL and the mean concentration (13,265.8+/-1,895.2 ng/mL) in these
      samples was the highest among other groups. The concentration in the other 50
      pleural effusion samples tested was <2,800 ng/mL. Defensins were mostly of the
      mature type in empyema. Pleural effusion levels of IL-8 and G-CSF in patients
      with empyema were also significantly higher than those in other samples. There
      was a significant correlation between defensins and IL-8 or G-CSF in pleural
      effusion fluid (r=0.762, and 0.827, respectively). CONCLUSIONS: Our results
      suggest that the high effusion concentrations of defensins in pleural effusion
      may constitute an important component of the host defense system or may have a
      cytotoxic role in empyema. Our results also indicate that the high levels of IL-8
      and G-CSF in empyema may indirectly explain the elevated levels of defensins by
      increasing the number of neutrophils in the pleural space.

PMID- 9515859
TI  - Comparisons of pleurodesis induced by talc with or without thymol iodide in
      rabbits.
AB  - STUDY OBJECTIVE: At the present time, talc administered either as a slurry or an
      aerosol is a popular agent for producing pleurodesis. Some investigators use
      iodized talc while others use plain talc. The purpose of the present study was to
      determine if iodized talc slurry produced a better pleurodesis in animals than
      did plain talc. DESIGN: New Zealand white male rabbits were randomly assigned to
      receive talc slurry, 200 mg/kg, with or without the addition of 50 mg iodide
      intrapleurally. Approximately 10 rabbits in each group were killed 1, 2, 4, 7,
      14, and 28 days after the injection. The amount and character of pleural fluid,
      the degree of pleural adhesions, and the microscopic changes were compared in the
      two different groups. RESULTS: The pleural fluid findings, the gross adhesion
      score for the pleura, and the microscopic changes in the visceral pleura were
      essentially identical for the rabbits that received iodized talc and those that
      received plain talc. The injection of both plain talc and iodized talc produced a
      normoglycemic exudative pleural effusion that had, for the most part, disappeared
      by the fourth day postinjection. The amount of pleural fluid at 48 h was 3.3+/
      0.6 mL in the plain talc and 2.2+/-0.5 mL in the iodized talc group. At 28 days,
      the mean degree of gross pleurodesis in the talc group was 2.6+/-0.2 compared
      with 2.3+/-0.2 in the iodized group, while the mean degree of microscopic
      fibrosis was 1.4+/-0.3 in the plain talc group compared with 2.0+/-0.3 in the
      iodized talc group. CONCLUSION: From this study, we conclude that the addition of
      50 mg of iodide does not improve the results with talc slurry pleurodesis in
      rabbits.

PMID- 9515860
TI  - A review of why and how we may use beta-blockers in congestive heart failure.
AB  - The history of the use of beta-blockers for congestive heart failure, beginning
      with the innovative seminal study by the Swedish group in 1975 to studies in
      1995, is reviewed and shows that almost all trials favored the use of beta
      blockers. They tended to demonstrate an increase in ejection fraction, a decrease
      in left ventricular mass, and in some studies, even a decrease in mortality. Even
      after the introduction of angiotensin-converting enzyme inhibitors, additional
      improvement in function and mortality was observed. Patients with nonischemic
      dilated cardiomyopathy derived more benefit from beta-blockers than did patients
      with ischemic cardiomyopathy. Least likely to benefit were patients treated for
      <2 months, patients with alcoholic cardiomyopathy, and those with marked
      intercellular fibrosis. Although the starting dose of metoprolol, the most common
      beta-blocker used, may have to be as low as 2.5 mg/d, mortality analysis failed
      to show a decrease in sudden death unless the dose was raised to about 300 mg/d,
      a dose at which beta-selectivity is generally not expected to be present. The non
      beta-specific bucindolol or carvedilol may ultimately be preferred to metoprolol
      because they are better tolerated initially due to a slight vasodilatation
      effect. Initial studies with carvedilol showed remarkable promise in reducing
      mortality. However, these agents cannot yet be said to have been studied
      adequately.

PMID- 9515861
TI  - Role of dobutamine stress echocardiography in heart transplant patients.
AB  - The objective of this focused review is to describe the rationale, methods, and
      potential clinical applications of dobutamine stress echocardiography (DSE) in
      heart transplant recipients. More than 500 studies in 150 heart transplant
      patients who underwent this procedure (1991-96) are reviewed. Relevant studies
      from the medical literature that have assessed the utility of DSE in the
      diagnosis of transplant coronary artery disease (TCAD) are discussed, the
      predictive ability of DSE for development of TCAD is determined, and the
      prognostic value of this test in the heart transplant population is evaluated.
      The protocol of DSE used in the laboratory for this study is presented and
      discussed with reference to other major studies that have determined the
      sensitivity, specificity, and positive and negative predictive accuracies. Since
      many noninvasive cardiac tests have not been consistently optimal to detect TCAD,
      a substantial number of patients undergo routine surveillance with coronary
      angiography to define the presence and magnitude of TCAD. Recent studies with DSE
      have shown it to be valuable in the noninvasive diagnosis of TCAD and to have an
      accuracy unmatched by other widely used imaging modalities. Other important
      evolving indications for DSE in heart transplant patients, such as prediction of
      prognosis and occurrence of cardiac events, are briefly discussed. Based on this
      study and the currently available literature, DSE appears to be a highly
      reproducible noninvasive test which can be serially employed in the routine
      surveillance of coronary artery disease in heart transplant patients.

PMID- 9515862
TI  - Effects of sampling interval on peak oxygen consumption in patients evaluated for
      heart transplantation.
AB  - BACKGROUND AND METHODS: Peak oxygen consumption is a commonly accepted criterion
      in patient selection for cardiac transplantation. To determine the effect of
      various gas exchange sampling intervals on the variability of peak oxygen
      consumption, 15 consecutive patients evaluated for cardiac transplantation
      performed maximal treadmill testing using a ramped protocol. Oxygen consumption
      was measured via breath-by-breath analysis of expired air. Peak oxygen
      consumption was determined for each test using the following sampling intervals:
      60-, 30-, and 15-s averages, eight breath rolling average, and true breath by
      breath. Variability of the mean peak oxygen consumption for each sample average
      was compared using analysis of variance on repeated measures. RESULTS AND
      CONCLUSIONS: Measures of peak oxygen consumption differed significantly (p<0.001)
      between sampling averages. A maximum variability of 20% was noted between the
      largest and smallest averages (13.8+/-4.2 mL/kg/min for 60 s vs 17.3+/-4.2
      mL/kg/min for breath by breath). No significant difference was found between the
      30-s, 15-s, and eight breath rolling averages (14.2+/-3.7 vs 14.5+/-3.9 vs 14.7+/
      4.3 mL/kg/min), respectively. Results of the study suggest (1) the sampling
      average can have a significant effect on peak oxygen consumption influencing
      patient selection for transplantation, and (2) sample averages larger than breath
      by breath but smaller than 60 s be used for determination of peak oxygen
      consumption.

PMID- 9515863
TI  - The role of radiologic imaging in diagnosing complications of video-assisted
      thoracoscopic surgery.
AB  - STUDY OBJECTIVE: To examine the role of radiologic imaging in evaluating
      complications of video-assisted thoracoscopic surgery. DESIGN: Retrospective
      review of radiographic and clinical data. SETTING: Tertiary referral hospital.
      PATIENTS: All patients who underwent thoracoscopy at the University of Maryland
      Hospital between July 1990 and June 1994. A total of 260 procedures were
      performed on 239 patients. MEASUREMENTS AND RESULTS: Imaging studies performed
      before, during, and after surgery in cases in which complications occurred were
      reviewed by two thoracic radiologists. A randomly selected group of 22 CT scans
      from uncomplicated cases were used as control subjects. Complications occurred in
      24 (9.2%) of the 260 thoracoscopic procedures. Intraoperative complications
      developed in 14 (5.4%) patients. Ten of the 14 patients had an obliterated
      pleural space that prevented access of the trocars and videoscope. Preoperative
      imaging showed significant pleural thickening or calcifications in seven of these
      ten patients. Other intraoperative complications were malposition of the double
      lumen endotracheal tube (n=2) and dislodgement of a localizing needle-wire (n=2).
      In 8 (3.1%) patients, radiographically evident postoperative complications
      developed; these complications included prolonged air leak, empyema, recurrent
      pneumothorax, pulmonary edema, and pneumonia. CONCLUSION: Pleural calcification
      or thickening that is found on preoperative studies may help predict difficulty
      in inserting the thoracoscopic instruments but also can be seen on preoperative
      CT scans in uncomplicated cases. Thoracic CT scans may fail to predict complete
      pleural symphysis.

PMID- 9515864
TI  - A patient with newly diagnosed melanoma and pulmonary nodules.

PMID- 9515865
TI  - Acute dyspnea and hypoxia in a 37-year-old woman with sarcoidosis.

PMID- 9515866
TI  - Rapidly progressive extensive subcutaneous emphysema associated with an
      implantable intratracheal oxygen catheter.
AB  - Localized subcutaneous emphysema is a recognized complication of transtracheal
      oxygen catheters. It usually occurs in the immediate postoperative period or in
      association with catheter tip migration. This is a case of rapidly progressive,
      extensive subcutaneous emphysema apparently resulting from paroxysms of coughing
      in a patient with a normally functioning implanted intratracheal oxygen catheter
      several weeks after placement.

PMID- 9515867
TI  - Successful treatment of Wegener's granulomatosis during pregnancy: a case report
      and review of the medical literature.
AB  - During the 18th week of a first pregnancy, a 20-year-old woman visits her
      physician complaining of cough, sore throat, and hemoptysis of 4 days in
      duration. A chest radiograph, laboratory study findings including a cytoplasmic
      antineutrophil cytoplasmic autoantibody titer, and lung biopsy results were
      consistent with a limited form of Wegener's granulomatosis. She was treated
      successfully with prednisone and cyclophosphamide. The remainder of her pregnancy
      was otherwise uneventful and resulted in a normal labor and delivery of a healthy
      male infant.

PMID- 9515868
TI  - Patient-induced complications of a Heimlich flutter valve.
AB  - Heimlich flutter valves have gained widespread acceptance in the treatment of
      pneumothorax. However, some features of their design may predispose them to
      inadvertent misuse. A case of tension pneumothorax is described which resulted
      from the insertion of a drinking straw into the Heimlich flutter valve assembly.

PMID- 9515869
TI  - Pseudomesotheliomatous adenocarcinoma of the lung in a patient with HIV
      infection.
AB  - Clinical and pathologic findings are presented of the first reported case in the
      English-language medical literature of pseudomesotheliomatous adenocarcinoma
      (PMA) occurring in an HIV-infected patient. PMA is an uncommon variant of
      peripheral lung cancer which typically occurs in elderly male patients. It mimics
      a malignant mesothelioma in terms of its clinical presentation and gross and
      microscopic appearance. The occurrence of this rare tumor in a young HIV-infected
      patient suggests some association between HIV infection and the development of
      PMA.

PMID- 9515870
TI  - Orbital herniation associated with noninvasive positive pressure ventilation.
AB  - A diagnosis of severe obstructive sleep apnea was made after a 52-year-old
      hypertensive man developed a large intracranial hemorrhage. Therapeutic
      noninvasive positive pressure ventilation (NPPV) for obstructive sleep apnea and
      hypoventilation was complicated by transient unilateral orbital herniation. As
      best as can be determined, this represents a new, potentially deleterious side
      effect of NPPV.

PMID- 9515871
TI  - Prophylaxis for deep venous thrombosis: the ACCP antithrombotic statement,
      revisited.

PMID- 9515872
TI  - Patient-centered ventilation.

PMID- 9515873
TI  - Treatment of Legionella lung abscess: unanswered questions?

PMID- 9515874
TI  - Nonspecific airway hyperresponsiveness in HIV disease.

PMID- 9515875
TI  - Usefulness of the flow volume loop.

PMID- 9515876
TI  - Amiodarone-induced adverse effects at the beginning of oral therapy: clinical
      implications.

PMID- 9515877
TI  - Urine thrombomodulin in patients with idiopathic pulmonary fibrosis.

PMID- 9515878
TI  - Airway obstruction with percutaneous tracheostomy.

PMID- 9515880
TI  - T-wave inversion in pulmonary embolism.

PMID- 9515879
TI  - More on airway obstruction with percutaneous tracheostomy.

PMID- 9515881
TI  - Asthma therapy clarified.

PMID- 9515882
TI  - Pulmonary hypertension and leukemia.

PMID- 9515883
TI  - Chronic necrotizing pulmonary aspergillosis: approach to management.

PMID- 9515884
TI  - Measuring nebulizer output.

PMID- 9515886
TI  - Disease Management of Pulmonary Infections. Proceedings of a conference.

PMID- 9515885
TI  - Patient selection for pulmonary artery catheterization.

PMID- 9515887
TI  - Do clinical practice guidelines define good medical care? The need for good
      science and the disclosure of uncertainty when defining 'best practices'.
AB  - Practice guidelines, although important in promoting quality, can also be harmful
      if they do not advocate the best options for patients. The latter can occur
      because of uncertainties in scientific evidence, biases in guideline development,
      and patient heterogeneity. Guidelines must therefore accurately describe the
      quality of the evidence and the degree of uncertainty that underlie
      recommendations. Proper methods for developing practice guidelines are reviewed.

PMID- 9515888
TI  - Does evidence-based medicine help the development of clinical practice
      guidelines?
AB  - Formal methods for the development of clinical practice guidelines have emerged
      to address societal needs to decrease physician practice variation, slow the rise
      of health-care costs, monitor inappropriate care, assist clinicians to stay
      abreast of new clinical information, set research priorities, and promote better
      health-care outcomes. Evidence-based methods ensure that guidelines provide valid
      recommendations based on a critical appraisal of the best available evidence
      rather than informal, opinion-based processes.

PMID- 9515889
TI  - Community-acquired pneumonia: a North American perspective.
AB  - The North American guidelines for pneumonia generally show agreement in both the
      Canadian and American approaches. However, much new data have appeared since the
      original recommendations, and revisions are needed. The general approach to
      empiric therapy that has been proposed in both the Canadian and American Thoracic
      Society documents does appear to be valid, and future recommendations will
      probably use the original approach as a framework for a more refined approach.

PMID- 9515890
TI  - Community-acquired pneumonia guidelines--an international comparison: a view from
      Europe.
AB  - Following an outline that details the pathogens causing community-acquired
      pneumonia (CAP) identified in studies from Europe, this article reviews the
      guidelines for the management of CAP in four European countries--France, Italy,
      Spain, and the United Kingdom. The method behind the development of each document
      is described, followed by a comparison of the scope of each document. All four
      documents provide guidelines for the management of two groups of patients--the
      severely ill and the nonseverely ill patient. A penicillin or macrolide feature
      for the nonseverely ill and the combination of a third-generation cephalosporin
      plus a macrolide for the severely ill patient are described in all four
      guidelines. Despite their different origins and methods, these four guidelines
      have more similarities than differences--the latter serving to emphasize some of
      the areas that require further research in this important condition. An important
      area for research is the impact that these guidelines have on practice and
      especially on clinical outcomes.

PMID- 9515891
TI  - Nosocomial pneumonia guidelines: an international perspective.
AB  - Hospital-acquired pneumonia is a serious illness with substantial morbidity and
      mortality. Management of this illness is challenging for the physician and a
      number of diverse issues must be considered when initiating therapy. Guidelines
      for the treatment of hospital-acquired pneumonia have been developed in Canada
      and the United States. A questionnaire sent to infectious disease physicians or
      clinical microbiologists in 29 countries showed that Australia, Sweden, and
      France had national guidelines in addition to Canada and the United States, while
      Hong Kong and France had single hospital-based guidelines. These guidelines are
      reviewed and some of the controversial issues relating to nosocomial pneumonia
      are discussed.

PMID- 9515892
TI  - Preventing mismanagement of community-acquired pneumonia at an urban public
      hospital: implications for institution-specific practice guidelines.
AB  - STUDY OBJECTIVES: To assess institutional performance of key diagnostic and
      therapeutic interventions and to identify areas amenable to improvement in the
      management of community-acquired pneumonia (CAP). DESIGN: A chart-based
      retrospective study. SETTING: Cook County Hospital, a large, urban, public
      teaching hospital. PATIENTS: Adult inpatients with a hospital discharge diagnosis
      of CAP. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Fifty hospital admissions
      were reviewed. Only 25 patients (50%) had two specimens obtained for blood
      culture, and sputum was sent for Gram's stain and culture for only 11 patients
      (22%). Approximately one third of the patients had portable anterior-posterior
      instead of standard posterior-anterior and lateral chest radiographs performed.
      Physicians in the emergency department (ED) tended to be less likely to note the
      presence of multilobar infiltrates or pleural effusions than the attending
      radiologists. The antibiotic regimens employed in the ED and on the inpatient
      wards were widely variable. The mean time from hospital entry until
      administration of the first dose of antibiotics was 5.5 h for the 18 patients for
      whom treatment was initiated in the ED vs 16.1 h for the 27 patients admitted
      through the ED for whom therapy was deferred until ward admission (p < 0.001,
      Student's t test). CONCLUSIONS: Institutional variations in the performance of
      basic diagnostic and therapeutic interventions for patients with CAP may be
      substantial. The local performance of these key processes of care should be
      assessed to help direct the formulation of institutional practice guidelines for
      the management of CAP.

PMID- 9515893
TI  - Acute exacerbations of chronic bronchitis: an international comparison.
AB  - The prevalence of chronic bronchitis is between 3% and 17% in most developed
      countries. However, higher rates in the range of 13 to 27% are encountered in
      less developed areas of the world. Acute exacerbations of chronic bronchitis
      (AECB) have usually been defined as the presence of increases in cough/sputum,
      sputum purulence, and dyspnea. However, recent investigations suggest that the
      severity of AECB may be divided into three stages based on the history of the
      patient: (1) previously healthy individuals; (2) patients with chronic cough and
      sputum and infrequent exacerbations; and (3) persons with frequent exacerbations
      or more severe chronic airflow limitation. Therapy for patients with less severe
      AECB include older and less expensive broad-spectrum antibiotics, while newer
      agents are indicated for patients with the most severe stage of AECB.

PMID- 9515894
TI  - How do we achieve cost-effective options in lower respiratory tract infection
      therapy?
AB  - Acute bronchitis and acute exacerbations of chronic bronchitis, common illnesses
      encountered by general and family physicians, account for approximately 14
      million physician visits per year. The pattern of antibiotic prescribing for
      these infections varies from country to country, but there is no clear rationale
      for these antimicrobial choices. A recent meta-analysis of all randomized,
      placebo-controlled trials of patients treated with antibiotics for acute
      exacerbations of chronic bronchitis concluded that a small but statistically
      significant improvement could be expected in antibiotic-treated patients.
      Haemophilus influenzae is the most commonly isolated organism from sputum in
      patients with acute exacerbations of chronic obstructive lung disease but other
      Haemophilus species, Streptococcus pneumoniae, and Moraxella catarrhalis may also
      be found. High-risk patients can be defined as being elderly, with significant
      impairment of lung function, having poor performance status with other comorbid
      conditions, having frequent exacerbations, and often requiring oral
      corticosteroid medication. Well-defined clinical trials measure efficacy of a
      drug but not the effectiveness in a real world situation. Future studies of new
      antimicrobials should examine their efficacy in patients with an increased risk
      of true bacterial infection.

PMID- 9515895
TI  - Sequential switch therapy for lower respiratory tract infections: a European
      perspective.
AB  - Traditionally, serious lower respiratory tract infections (LRTIs) are treated in
      hospital and with parenteral antibiotics. During the past decade, there has been
      an impetus to reduce the overall cost of antimicrobial therapy. The availability
      of new oral antibiotics with superior pharmacokinetics profiles and safety has
      enabled clinicians increasingly to consider their use in managing serious
      infections effectively. This article reviews the current published literature
      regarding the practice of switch therapy for LRTIs, examining the evidence for
      efficacy, safety, appropriate timing of the switch, the economic benefits, and
      the suitability of various antibiotics. There is an emphasis on comparing current
      European and US experience and examining key strategies in implementing such
      programs and means of assessing their impact.

PMID- 9515896
TI  - Diagnosis of lower respiratory tract infections: what we have and what would be
      nice.
AB  - STUDY OBJECTIVES: To review the various methods used to diagnose lower
      respiratory tract infections. DESIGN: Review of literature with appropriate
      references to various techniques proposed to diagnose pneumonia. INTERVENTION:
      Compare and contrast different proposed approaches to diagnose pneumonia.
      RESULTS: Bronchoscopic techniques appear more clear cut for certain nonbacterial
      pathogens. Their role in immunocompromised patients is more clear cut, while in
      the nonimmunocompromised patient, invasive diagnostic techniques probably provide
      a higher certainty of the final diagnosis of the patient. Recent interest has
      focused on nonbronchoscopic techniques for the mechanically ventilated patient.
      None of these techniques has been demonstrated to change clinical outcome.
      CONCLUSIONS: Diagnosis of lower respiratory tract infection has to be tailored
      for the individual patient. Decision about which procedure to do is influenced by
      the patient's underlying immune status, level of illness, and response to empiric
      therapy.

PMID- 9515897
TI  - Cytokine modifiers: pipe dream or reality?
AB  - Therapies that block the actions of interleukin-1 (IL-1) or tumor necrosis factor
      alpha (TNF-alpha) have been proposed to be potentially beneficial in critically
      ill patients with sepsis. Clinical trials demonstrated no survival benefit when
      the actions of IL-1 were blocked. In contrast, inhibition of TNF-alpha with
      either monoclonal antibodies or TNF receptor fusion proteins appeared to improve
      survival in prospectively defined groups of patients with severe sepsis,
      including those with dysfunction of two or more organ systems or with septic
      shock associated with the dysfunction of at least one organ system. Although none
      of the clinical trials has demonstrated statistically significant improvements in
      mortality for patients who received anticytokine therapy 28 days before, few of
      the completed studies were initially powered to achieve statistical significance
      at the day 28 end point. While the available data suggest that anti-TNF therapies
      improve survival in groups of patients with sepsis that can be identified by
      clinical criteria, confirmation of the potentially beneficial effects of anti-TNF
      agents awaits completion of the large multicenter clinical trials that are
      presently examining the utility of these therapies.

PMID- 9515898
TI  - Strategies and options for minimizing resistance emergence in pulmonary
      infections.
AB  - The early-onset hospital pulmonary gram-negative infections may respond to
      ciprofloxacin and co-amoxiclav without significant resistance development.
      Penicillin-resistant Streptococcus pneumoniae may be treated with macrolides,
      fluoroquinolones, and glycopeptides. The late-onset hospital pathogens all seem
      to have developed resistance to cephalosporins, so greater reliance is now made
      on the fluoroquinolones and carbapenems when aminoglycoside therapy is considered
      undesirable.

PMID- 9515899
TI  - When an ATPase is not an ATPase: at low temperatures the C-terminal domain of the
      ABC transporter CvaB is a GTPase.
AB  - The ATP-binding cassette (ABC) transporters belong to a large superfamily of
      proteins which share a common function and a common nucleotide-binding domain.
      The CvaB protein from Escherichia coli is a member of the bacterial ABC exporter
      subfamily and is essential for the export of the peptide antibiotic colicin V.
      Here we report that, surprisingly, the CvaB carboxyl-terminal nucleotide-binding
      domain (BCTD) can be preferentially cross-linked to GTP but not to ATP at low
      temperatures. The cross-linking is Mg2+ and Mn2+ dependent. However, BCTD
      possesses similar GTPase and ATPase activities at 37 degrees C, with the same
      kinetic parameters and with similar responses to inhibitors. Moreover, a point
      mutation (D654H) in CvaB that completely abolishes colicin V secretion severely
      impairs both GTPase and ATPase activities in the corresponding BCTD, indicating
      that the two activities are from the same enzyme. Interestingly, hydrolysis
      activity of ATP is much more cold sensitive than that of GTP: BCTD possesses
      mainly GTP hydrolysis activity at 10 degrees C, consistent with the cross-linking
      results. These findings suggest a novel mechanism for an ABC protein-mediated
      transport with specificity for GTP hydrolysis.

PMID- 9515902
TI  - Contribution of the disulfide bond of the A subunit to the action of Escherichia
      coli heat-labile enterotoxin.
AB  - Escherichia coli heat-labile enterotoxin (LT) consists of an A subunit and five B
      subunits. These subunits oligomerize into an assembled holotoxin within the
      periplasm. Structural analysis of LT has revealed that the A subunit interacts
      with the B subunit through its carboxy terminus. This indicates that the carboxy
      terminal portion of the protein is required for assembly of holotoxin in the
      periplasm. However, it is not known whether other regions of the A subunit
      contribute to the assembly. The A subunit constituting the holotoxin contains a
      disulfide bond between Cys-187 and Cys-199. It has been observed in many proteins
      that the intramolecular disulfide bond is deeply involved in the function and
      tertiary structure of the protein. We speculated that the disulfide bond of the A
      subunit contributes to the assembly in the periplasm, although the bond is not a
      structural element of the carboxy-terminal portion of the A subunit. We replaced
      these cysteine residues of the A subunit by oligonucleotide-directed site
      specific mutagenesis and analyzed the LTs produced by cells containing the mutant
      LT genes. The amount of the mutant holotoxin produced was small compared with
      that of the wild-type strain, indicating that the disulfide bond of the A subunit
      contributes to the structure which functions as the site of nucleation in the
      assembly. A reconstitution experiment in vitro supported the notion.
      Subsequently, we found that the mutant A subunit constituting holotoxin is easily
      degraded by trypsin and that in cells incubated with mutant LTs, the lag until
      the intracellular cyclic AMP begins to accumulate is longer than in cells
      incubated with native LTs. These results might be useful for the analysis of the
      interaction of LT with target cells at the molecular level.

PMID- 9515901
TI  - Growth phase and temperature influence promoter activity, transcript abundance,
      and protein stability during biosynthesis of the Pseudomonas syringae phytotoxin
      coronatine.
AB  - The plant-pathogenic bacterium Pseudomonas syringae pv. glycinea PG4180.N9
      synthesizes high levels of the polyketide phytotoxin coronatine (COR) at 18
      degrees C, whereas no detectable toxin is produced at 28 degrees C. Previously,
      we reported that the temperature-sensitive activation of three promoters within
      the COR biosynthetic gene cluster might explain thermoregulation of COR
      biosynthesis. The present study was aimed at furthering our understanding of the
      transcriptional as well as the posttranslational effects of temperature on
      expression of cmaB, which encodes an enzyme involved in COR biosynthesis.
      Transcriptional fusions using a promoterless glucuronidase gene and Northern blot
      analyses were used to monitor promoter activities and transcript abundance for
      the cmaABT operon during bacterial growth at 18 and 28 degrees C. Promoter
      activity and transcription rates were maximal when cells were incubated at 18
      degrees C and sampled at mid-logarithmic phase. Transcription declined moderately
      during the transition to stationary phase but remained higher at 18 C than at 28
      degrees C. Western blot analysis indicated that CmaB accumulated in the late
      stationary phase of P. syringae cultures grown at 18 degrees C but not in
      cultures incubated at 28 degrees C. Temperature shift experiments indicated that
      CmaB stability was more pronounced at 18 degrees C than at 28 degrees C. Although
      temperature has a strong impact on transcription of COR biosynthetic genes, we
      propose that thermoregulation of protein stability might also control COR
      synthesis.

PMID- 9515900
TI  - Cloning and sequencing of a 2,5-dichlorohydroquinone reductive dehalogenase gene
      whose product is involved in degradation of gamma-hexachlorocyclohexane by
      Sphingomonas paucimobilis.
AB  - Sphingomonas (formerly Pseudomonas) paucimobilis UT26 utilizes gamma
      hexachlorocyclohexane (gamma-HCH), a halogenated organic insecticide, as a sole
      carbon and energy source. In a previous study, we showed that gamma-HCH is
      degraded to 2,5-dichlorohydroquinone (2,5-DCHQ) (Y. Nagata, R. Ohtomo, K.
      Miyauchi, M. Fukuda, K. Yano, and M. Takagi, J. Bacteriol. 176:3117-3125, 1994).
      In the present study, we cloned and characterized a gene, designated linD,
      directly involved in the degradation of 2,5-DCHQ. The linD gene encodes a peptide
      of 343 amino acids and has a low level of similarity to proteins which belong to
      the glutathione S-transferase family. When LinD was overproduced in Escherichia
      coli, a 40-kDa protein was found after sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis. Northern blot analysis revealed that expression of the linD gene
      was induced by 2,5-DCHQ in S. paucimobilis UT26. Thin-layer chromatography and
      gas chromatography-mass spectrometry analyses with the LinD-overexpressing E.
      coli cells revealed that LinD converts 2,5-DCHQ rapidly to chlorohydroquinone
      (CHQ) and also converts CHQ slowly to hydroquinone. LinD activity in crude cell
      extracts was increased 3.7-fold by the addition of glutathione. All three of the
      Tn5-induced mutants of UT26, which lack 2,5-DCHQ dehalogenase activity, had
      rearrangements or a deletion in the linD region. These results indicate that LinD
      is a glutathione-dependent reductive dehalogenase involved in the degradation of
      gamma-HCH by S. paucimobilis UT26.

PMID- 9515904
TI  - An rne-1 pnp-7 double mutation suppresses the temperature-sensitive defect of
      lacZ gene expression in a divE mutant.
AB  - A divE mutant, which has a temperature-sensitive mutation in the tRNA1Ser gene,
      exhibits differential loss of the synthesis of certain proteins, such as beta
      galactosidase and succinate dehydrogenase, at nonpermissive temperatures. In
      Escherichia coli, the UCA codon is recognized only by tRNA1Ser. Several genes
      containing UCA codons are normally expressed after a temperature shift to 42
      degrees C in the divE mutant. Therefore, it is unlikely that the defect in
      protein synthesis at 42 degrees C is simply caused by a defect in the decoding
      function of the mutant tRNA1Ser. In this study, we sought to determine the cause
      of the defect in lacZ gene expression in the divE mutant. It has also been shown
      that the defect in lacZ gene expression is accompanied by a decrease in the
      amount of lacZ mRNA. To examine whether inactivation of mRNA degradation pathways
      restores the defect in lacZ gene expression, we constructed divE mutants
      containing rne-1, rnb-500, and pnp-7 mutations in various combinations. We found
      that the defect was almost completely restored by introducing an rne-1 pnp-7
      double mutation into the divE mutant. Northern hybridization analysis showed that
      the rne-1 mutation stabilized lacZ mRNA, whereas the pnp-7 mutation stabilized
      mutant tRNA1Ser, at 44 degrees C. We present a mechanism that may explain these
      results.

PMID- 9515903
TI  - Regulation and characterization of a newly deduced cell wall hydrolase gene
      (cwlJ) which affects germination of Bacillus subtilis spores.
AB  - The predicted amino acid sequence of Bacillus subtilis ycbQ (renamed cwlJ)
      exhibits high similarity to those of the deduced C-terminal catalytic domain of
      SleBs, the specific cortex-hydrolyzing enzyme of B. cereus and the deduced one of
      B. subtilis. We constructed a cwlJ::lacZ fusion in the B. subtilis chromosome.
      The beta-galactosidase activity and results of Northern hybridization and primer
      extension analyses of the cwlJ gene indicated that it is transcribed by EsigmaE
      RNA polymerase. cwlJ-deficient spores responded to both L-alanine and AGFK, the
      A580 values of spore suspensions decreased more slowly than in the case of the
      wild-type strain, and the mutant spores released less dipicolinic acid than did
      those of the wild-type strain during germination. However, the mutant spores
      released only slightly less hexosamine than did the wild-type spores. In
      contrast, B. subtilis sleB spores did not release hexosamine at a significant
      level. While cwlJ and sleB spores were able to germinate, CJSB (cwlJ sleB) spores
      could not germinate but exhibited initial germination reactions, e.g., partial
      decrease in A580 and slow release of dipicolinic acid. CJSB spores became
      slightly gray after 6 h in the germinant, but their refractility was much greater
      than that of sleB mutant spores. The roles of the sleB and cwlJ mutations in
      germination and spore maturation are also discussed.

PMID- 9515905
TI  - Identification of a sequence motif that confers SecB dependence on a SecB
      independent secretory protein in vivo.
AB  - SecB is a cytosolic chaperone which facilitates the transport of a subset of
      proteins, including membrane proteins such as PhoE and LamB and some periplasmic
      proteins such as maltose-binding protein, in Escherichia coli. However, not all
      proteins require SecB for transport, and proteins such as ribose-binding protein
      are exported efficiently even in SecB-null strains. The characteristics which
      confer SecB dependence on some proteins but not others have not been defined. To
      determine the sequence characteristics that are responsible for the SecB
      requirement, we have inserted a systematic series of short, polymeric sequences
      into the SecB-independent protein alkaline phosphatase (PhoA). The extent to
      which these simple sequences convert alkaline phosphatase into a SecB-requiring
      protein was evaluated in vivo. Using this approach we have examined the roles of
      the polarity and charge of the sequence, as well as its location within the
      mature region, in conferring SecB dependence. We find that an insert with as few
      as 10 residues, of which 3 are basic, confers SecB dependence and that the mutant
      protein is efficiently exported in the presence of SecB. Remarkably, the basic
      motifs caused the protein to be translocated in a strict membrane potential
      dependent fashion, indicating that the membrane potential is not a barrier to,
      but rather a requirement for, translocation of the motif. The alkaline
      phosphatase mutants most sensitive to the loss of SecB are those most sensitive
      to inhibition of SecA via azide treatment, consistent with the necessity for
      formation of a preprotein-SecB-SecA complex. Furthermore, the impact of the basic
      motif depends on location within the mature protein and parallels the
      accessibility of the location to the secretion apparatus.

PMID- 9515906
TI  - Balance between endogenous superoxide stress and antioxidant defenses.
AB  - Cells devoid of cytosolic superoxide dismutase (SOD) suffer enzyme inactivation,
      growth deficiencies, and DNA damage. It has been proposed that the scant
      superoxide (O2-) generated by aerobic metabolism harms even cells that contain
      abundant SOD. However, this idea has been difficult to test. To determine the
      amount of O2- that is needed to cause these defects, we modulated the O2-
      concentration inside Escherichia coli by controlling the expression of SOD. An
      increase in O2- of more than twofold above wild-type levels substantially
      diminished the activity of labile dehydratases, an increase in O2- of any more
      than fourfold measurably impaired growth, and a fivefold increase in O2-
      sensitized cells to DNA damage. These results indicate that E. coli
      constitutively synthesizes just enough SOD to defend biomolecules against
      endogenous O2- so that modest increases in O2- concentration diminish cell
      fitness. This conclusion is in excellent agreement with quantitative predictions
      based upon previously determined rates of intracellular O2- production, O2-
      dismutation, dehydratase inactivation, and enzyme repair. The vulnerability of
      bacteria to increased intracellular O2- explains the widespread use of superoxide
      producing drugs as bactericidal weapons in nature. E. coli responds to such drugs
      by inducing the SoxRS regulon, which positively regulates synthesis of SOD and
      other defensive proteins. However, even toxic amounts of endogenous O2- did not
      activate SoxR, and SoxR activation by paraquat was not at all inhibited by excess
      SOD. Therefore, in responding to redox-cycling drugs, SoxR senses some signal
      other than O2-.

PMID- 9515907
TI  - The LysR-type transcriptional regulator CbbR controlling autotrophic CO2 fixation
      by Xanthobacter flavus is an NADPH sensor.
AB  - Autotrophic growth of Xanthobacter flavus is dependent on the fixation of carbon
      dioxide via the Calvin cycle and on the oxidation of simple organic and inorganic
      compounds to provide the cell with energy. Maximal induction of the cbb and gap
      pgk operons encoding enzymes of the Calvin cycle occurs in the absence of
      multicarbon substrates and the presence of methanol, formate, hydrogen, or
      thiosulfate. The LysR-type transcriptional regulator CbbR regulates the
      expression of the cbb and gap-pgk operons, but it is unknown to what cellular
      signal CbbR responds. In order to study the effects of low-molecular-weight
      compounds on the DNA-binding characteristics of CbbR, the protein was expressed
      in Escherichia coli and subsequently purified to homogeneity. CbbR of X. flavus
      is a dimer of 36-kDa subunits. DNA-binding assays suggested that two CbbR
      molecules bind to a 51-bp DNA fragment on which two inverted repeats containing
      the LysR motif are located. The addition of 200 microM NADPH, but not NADH,
      resulted in a threefold increase in DNA binding. The apparent K(dNADPH) of CbbR
      was determined to be 75 microM. By using circular permutated DNA fragments, it
      was shown that CbbR introduces a 64 degree bend in the DNA. The presence of NADPH
      in the DNA-bending assay resulted in a relaxation of the DNA bend by 9 degree.
      From the results of these in vitro experiments, we conclude that CbbR responds to
      NADPH. The in vivo regulation of the cbb and gap-pgk operons may therefore be
      regulated by the intracellular concentration of NADPH.

PMID- 9515908
TI  - Loss of the plasma membrane-bound protein Gas1p in Saccharomyces cerevisiae
      results in the release of beta1,3-glucan into the medium and induces a
      compensation mechanism to ensure cell wall integrity.
AB  - Deletion of GAS1/GGP1/CWH52 results in a lower beta-glucan content of the cell
      wall and swollen, more spherical cells (L. Popolo, M. Vai, E. Gatti, S. Porello,
      P. Bonfante, R. Balestrini, and L. Alberghina, J. Bacteriol. 175:1879-1885, 1993;
      A. F. J. Ram, S. S. C. Brekelmans, L. J. W. M. Oehlen, and F. M. Klis, FEBS Lett.
      358:165-170, 1995). We show here that gas1delta cells release beta1,3-glucan into
      the medium. Western analysis of the medium proteins with beta1,3-glucan- and
      beta1,6-glucan-specific antibodies showed further that at least some of the
      released beta1,3-glucan was linked to protein as part of a beta1,3-glucan-beta1,6
      glucan-protein complex. These data indicate that Gas1p might play a role in the
      retention of beta1,3-glucan and/or beta-glucosylated proteins. Interestingly, the
      defective incorporation of beta1,3-glucan in the cell wall was accompanied by an
      increase in chitin and mannan content in the cell wall, an enhanced expression of
      cell wall protein 1 (Cwp1p), and an increase in beta1,3-glucan synthase activity,
      probably caused by the induced expression of Fks2p. It is proposed that the cell
      wall weakening caused by the loss of Gas1p induces a set of compensatory
      reactions to ensure cell integrity.

PMID- 9515909
TI  - A conserved histidine is essential for glycerolipid acyltransferase catalysis.
AB  - Sequence analysis of membrane-bound glycerolipid acyltransferases revealed that
      proteins from the bacterial, plant, and animal kingdoms share a highly conserved
      domain containing invariant histidine and aspartic acid residues separated by
      four less conserved residues in an HX4D configuration. We investigated the role
      of the invariant histidine residue in acyltransferase catalysis by site-directed
      mutagenesis of two representative members of this family, the sn-glycerol-3
      phosphate acyltransferase (PlsB) and the bifunctional 2-acyl
      glycerophosphoethanolamine acyltransferase/acyl-acyl carrier protein synthetase
      (Aas) of Escherichia coli. Both the PlsB[H306A] and Aas[H36A] mutants lacked
      acyltransferase activity. However, the Aas[H36A] mutant retained significant acyl
      acyl carrier protein synthetase activity, illustrating that the lack of
      acyltransferase activity was specifically associated with the H36A substitution.
      The invariant aspartic acid residue in the HX4D pattern was also important. The
      substitution of aspartic acid 311 with glutamic acid in PlsB resulted in an
      enzyme with significantly reduced catalytic activity. Substitution of an alanine
      at this position eliminated acyltransferase activity; however, the PlsB[D311A]
      mutant protein did not assemble into the membrane, indicating that aspartic acid
      311 is also important for the proper folding and membrane insertion of the
      acyltransferases. These data are consistent with a mechanism for glycerolipid
      acyltransferase catalysis where the invariant histidine functions as a general
      base to deprotonate the hydroxyl moiety of the acyl acceptor.

PMID- 9515910
TI  - External loops at the C terminus of Erwinia chrysanthemi pectate lyase C are
      required for species-specific secretion through the out type II pathway.
AB  - The type II secretion system (main terminal branch of the general secretion
      pathway) is used by diverse gram-negative bacteria to secrete extracellular
      proteins. Proteins secreted by this pathway are synthesized with an N-terminal
      signal peptide which is removed upon translocation across the inner membrane, but
      the signals which target the mature proteins for secretion across the outer
      membrane are unknown. The plant pathogens Erwinia chrysanthemi and Erwinia
      carotovora secrete several isozymes of pectate lyase (Pel) by the out-encoded
      type II pathway. However, these two bacteria cannot secrete Pels encoded by
      heterologously expressed pel genes from the other species, suggesting the
      existence of species-specific secretion signals within these proteins. The
      functional cluster of E. chrysanthemi out genes carried on cosmid pCPP2006
      enables Escherichia coli to secrete E. chrysanthemi, but not E. carotovora, Pels.
      We exploited the high sequence similarity between E. chrysanthemi PelC and E.
      carotovora Pel1 to construct 15 hybrid proteins in which different regions of
      PelC were replaced with homologous sequences from Pell. The differential
      secretion of these hybrid proteins by E. coli(pCPP2006) revealed M118 to D175 and
      V215 to C329 as regions required for species-specific secretion of PelC. We
      propose that the primary targeting signal is contained within the external loops
      formed by G274 to C329 but is dependent on residues in M118 to D170 and V215 to
      G274 for proper positioning.

PMID- 9515911
TI  - Altered srf expression in Bacillus subtilis resulting from changes in culture pH
      is dependent on the Spo0K oligopeptide permease and the ComQX system of
      extracellular control.
AB  - The expression of the srf operon of Bacillus subtilis, encoding surfactin
      synthetase and the competence regulatory protein ComS, was observed to be reduced
      when cells were grown in a rich glucose- and glutamine-containing medium in which
      late-growth culture pH was 5.0 or lower. The production of the surfactin
      synthetase subunits and of surfactin itself was also reduced. Raising the pH to
      near neutrality resulted in dramatic increases in srf expression and surfactin
      production. This apparent pH-dependent induction of srf expression required
      spo0K, which encodes the oligopeptide permease that functions in cell-density
      dependent control of sporulation and competence, but not CSF, the competence
      inducing pheromone that regulates srf expression in a Spo0K-dependent manner.
      Both ComP and ComA, the two-component regulatory pair that stimulates cell
      density-dependent srf transcription, were required for optimal expression of srf
      at low and high pHs, but ComP was not required for pH-dependent srf induction.
      The known negative regulators of srf, RapC and CodY, were found not to function
      significantly in pH-dependent srf expression. Late-growth culture supernatants at
      low pH were not active in inducing srf expression in cells of low-density
      cultures but were rendered active when their pH was raised to near neutrality.
      ComQ (and very likely the srf-inducing pheromone ComX) and Spo0K were found to be
      required for the extracellular induction of srf-lacZ at neutral pH. The results
      suggest that srf expression, in response to changes in culture pH, requires Spo0K
      and another, as yet unidentified, extracellular factor. The study also provides
      evidence consistent with the hypothesis that ComP acts both positively and
      negatively in the regulation of ComA and that both activities are controlled by
      the ComX pheromone.

PMID- 9515912
TI  - IroN, a novel outer membrane siderophore receptor characteristic of Salmonella
      enterica.
AB  - Speciation in enterobacteria involved horizontal gene transfer. Therefore,
      analysis of genes acquired by horizontal transfer that are present in one species
      but not its close relatives is expected to give insights into how new bacterial
      species were formed. In this study we characterize iroN, a gene located
      downstream of the iroBC operon in the iroA locus of Salmonella enterica serotype
      Typhi. Like iroBC, the iroN gene is present in all phylogenetic lineages of S.
      enterica but is absent from closely related species such as Salmonella bongori or
      Escherichia coli. Comparison of the deduced amino acid sequence of iroN with
      other proteins suggested that this gene encodes an outer membrane siderophore
      receptor protein. Mutational analysis in S. enterica and expression in E. coli
      identified a 78-kDa outer membrane protein as the iroN gene product. When
      introduced into an E. coli fepA cir fiu aroB mutant on a cosmid, iroN mediated
      utilization of structurally related catecholate siderophores, including N-(2,3
      dihydroxybenzoyl)-L-serine, myxochelin A, benzaldehyde-2,3
      dihydroxybenzhydrazone, 2-N,6-N-bis(2,3-dihydroxybenzoyl)-L-lysine, 2-N,6-N
      bis(2,3-dihydroxybenzoyl)-L-lysine amide, and enterochelin. These results suggest
      that the iroA locus functions in iron acquisition in S. enterica.

PMID- 9515913
TI  - Import and metabolism of glutathione by Streptococcus mutans.
AB  - Glutathione (gamma-GluCysGly, GSH) is not found in most gram-positive bacteria,
      but some appear to synthesize it and others, including Streptococcus mutans ATCC
      33402, import it from their growth medium. Import of oxidized glutathione (GSSG)
      by S. mutans 33402 in 7H9 medium was shown to require glucose and to occur with
      an apparent Km of 18+/-5 microM. GSSG, GSH, S-methylglutathione, and homocysteine
      glutathione mixed disulfide (hCySSG) were imported at comparable rates (measured
      by depletion of substrate in the medium), as was the disulfide of gamma-GluCys.
      In contrast, the disulfide of CysGly was not taken up at a measurable rate,
      indicating that the gamma-Glu residue is important for efficient transport.
      During incubation with GSSG, little GSSG was detected in cells but GSH and gamma
      GluCys accumulated during the first 30 min and then declined. No significant
      intracellular accumulation of Cys or sulfide was found. Transient intracellular
      accumulation of D/L-homocysteine, as well as GSH and gamma-GluCys, was observed
      during import of hCySSG. Although substantial levels of GSH were found in cells
      when S. mutans was grown on media containing glutathione, such GSH accumulation
      had no effect on the growth rate. However, the presence of cellular GSH did
      protect against growth inhibition by the thiol-oxidizing agent diamide. Import of
      glutathione by S. mutans ATCC 25175, which like strain 33402 does not synthesize
      glutathione, occurred at a rate comparable to that of strain 33402, but three
      species which appear to synthesize glutathione (S. agalactiae ATCC 12927, S.
      pyogenes ATCC 8668, and Enterococcus faecalis ATCC 29212) imported glutathione at
      negligible or markedly lower rates.

PMID- 9515914
TI  - Unusual organization of the genes coding for HydSL, the stable [NiFe]hydrogenase
      in the photosynthetic bacterium Thiocapsa roseopersicina BBS.
AB  - The characterization of a hyd gene cluster encoding the stable, bidirectional
      [NiFe]hydrogenase 1 enzyme in Thiocapsa roseopersicina BBS, a purple sulfur
      photosynthetic bacterium belonging to the family Chromatiaceae, is presented. The
      heterodimeric hydrogenase 1 had been purified to homogeneity and thoroughly
      characterized (K. L. Kovacs et al., J. Biol. Chem. 266:947-951, 1991; C. Bagyinka
      et al., J. Am. Chem. Soc. 115:3567-3585, 1993). As an unusual feature, a 1,979-bp
      intergenic sequence (IS) separates the structural genes hydS and hydL, which
      encode the small and the large subunits, respectively. This IS harbors two
      sequential open reading frames (ORFs) which may code for electron transfer
      proteins ISP1 and ISP2. ISP1 and ISP2 are homologous to ORF5 and ORF6 in the hmc
      operon, coding for a transmembrane electron transfer complex in Desulfovibrio
      vulgaris. Other accessory proteins are not found immediately downstream or
      upstream of hydSL. A hup gene cluster coding for a typical hydrogen uptake
      [NiFe]hydrogenase in T. roseopersicina was reported earlier (A. Colbeau et al.
      Gene 140:25-31, 1994). The deduced amino acid sequences of the two small (hupS
      and hydS) and large subunit (hupL and hydL) sequences share 46 and 58% identity,
      respectively. The hup and hyd genes differ in the arrangement of accessory genes,
      and the genes encoding the two enzymes are located at least 15 kb apart on the
      chromosome. Both hydrogenases are associated with the photosynthetic membrane. A
      stable and an unstable hydrogenase activity can be detected in cells grown under
      nitrogen-fixing conditions; the latter activity is missing in cells supplied with
      ammonia as the nitrogen source. The apparently constitutive and stable activity
      corresponds to hydrogenase 1, coded by hydSL, and the inducible and unstable
      second hydrogenase may be the product of the hup gene cluster.

PMID- 9515915
TI  - Physiological and genetic analyses leading to identification of a biochemical
      role for the moeA (molybdate metabolism) gene product in Escherichia coli.
AB  - A unique class of chlorate-resistant mutants of Escherichia coli which produced
      formate hydrogenlyase and nitrate reductase activities only when grown in medium
      with limiting amounts of sulfur compounds was isolated. These mutants failed to
      produce the two molybdoenzyme activities when cultured in rich medium or glucose
      minimal medium. The mutations in these mutants were localized in the moeA gene.
      Mutant strains with polar mutations in moeA which are also moeB did not produce
      active molybdoenzymes in any of the media tested. moeA mutants with a second
      mutation in either cysDNCJI or cysH gene lost the ability to produce active
      molybdoenzyme even when grown in medium limiting in sulfur compounds. The
      CysDNCJIH proteins along with CysG catalyze the conversion of sulfate to sulfide.
      Addition of sulfide to the growth medium of moeA cys double mutants suppressed
      the MoeA- phenotype. These results suggest that in the absence of MoeA protein,
      the sulfide produced by the sulfate activation/reduction pathway combines with
      molybdate in the production of activated molybdenum. Since hydrogen sulfide is
      known to interact with molybdate in the production of thiomolybdate, it is
      possible that the MoeA-catalyzed activated molybdenum is a form of thiomolybdenum
      species which is used in the synthesis of molybdenum cofactor from Mo-free
      molybdopterin.

PMID- 9515916
TI  - Helicobacter pylori ribBA-mediated riboflavin production is involved in iron
      acquisition.
AB  - In this study, we cloned and sequenced a DNA fragment from an ordered cosmid
      library of Helicobacter pylori NCTC 11638 which confers to a siderophore
      synthesis mutant of Escherichia coli (EB53 aroB hemA) the ability to grow on iron
      restrictive media and to reduce ferric iron. Sequence analysis of the DNA
      fragment revealed the presence of an open reading frame with high homology to the
      ribA gene of Bacillus subtilis. This gene encodes a bifunctional enzyme with the
      activities of both 3,4-dihydroxy-2-butanone 4-phosphate (DHBP) synthase and GTP
      cyclohydrolase II, which catalyze two essential steps in riboflavin biosynthesis.
      Expression of the gene (designated ribBA) resulted in the formation of one
      translational product, which was able to complement both the ribA and the ribB
      mutation in E. coli. Expression of ribBA was iron regulated, as was suggested by
      the presence of a putative FUR box in its promotor region and as shown by RNA dot
      blot analysis. Furthermore, we showed that production of riboflavin in H. pylori
      cells is iron regulated. E. coli EB53 containing the plasmid with H. pylori ribBA
      excreted riboflavin in the culture medium, and this riboflavin excretion also
      appeared to be iron regulated. We postulate that the iron-regulated production of
      riboflavin and ferric-iron-reduction activity by E. coli EB53 transformed with
      the H. pylori ribBA gene is responsible for the survival of EB53 on iron
      restrictive medium. Because disruption of ribBA in H. pylori eliminates its
      ferric-iron-reduction activity, we conclude that ribBA has an important role in
      ferric-iron reduction and iron acquisition by H. pylori.

PMID- 9515917
TI  - Biochemical characterization of the 20S proteasome from the methanoarchaeon
      Methanosarcina thermophila.
AB  - The 20S proteasome from the methanoarchaeon Methanosarcina thermophila was
      produced in Escherichia coli and characterized. The biochemical properties
      revealed novel features of the archaeal 20S proteasome. A fully active 20S
      proteasome could be assembled in vitro with purified native alpha ring structures
      and beta prosubunits independently produced in Escherichia coli, which
      demonstrated that accessory proteins are not essential for processing of the beta
      prosubunits or assembly of the 20S proteasome. A protein complex with a molecular
      mass intermediate to those of the alpha7 ring and the 20S proteasome was
      detected, suggesting that the 20S proteasome is assembled from precursor
      complexes. The heterologously produced M. thermophila 20S proteasome
      predominately catalyzed cleavage of peptide bonds carboxyl to the acidic residue
      Glu (postglutamyl activity) and the hydrophobic residues Phe and Tyr
      (chymotrypsinlike activity) in short chromogenic and fluorogenic peptides. Low
      level hydrolyzing activities were also detected carboxyl to the acidic residue
      Asp and the basic residue Arg (trypsinlike activity). Sodium dodecyl sulfate and
      divalent or monovalent ions stimulated chymotrypsinlike activity and inhibited
      postglutamyl activity, whereas ATP stimulated postglutamyl activity but had
      little effect on the chymotrypsinlike activity. The results suggest that the 20S
      proteasome is a flexible protein which adjusts to binding of substrates. The 20S
      proteasome also hydrolyzed large proteins. Replacement of the nucleophilic Thr1
      residue with an Ala in the beta subunit abolished all activities, which suggests
      that only one active site is responsible for the multisubstrate activity.
      Replacement of beta subunit active-site Lys33 with Arg reduced all activities,
      which further supports the existence of one catalytic site; however, this result
      also suggests a role for Lys33 in polarization of the Thr1 N, which serves to
      strip a proton from the active-site Thr1 Ogamma nucleophile. Replacement of Asp51
      with Asn had no significant effect on trypsinlike activity, enhanced postglutamyl
      and trypsinlike activities, and only partially reduced lysozyme-hydrolyzing
      activity, which suggested that this residue is not essential for multisubstrate
      activity.

PMID- 9515918
TI  - The S-layer proteins of two Bacillus stearothermophilus wild-type strains are
      bound via their N-terminal region to a secondary cell wall polymer of identical
      chemical composition.
AB  - Two Bacillus stearothermophilus wild-type strains were investigated regarding a
      common recognition and binding mechanism between the S-layer protein and the
      underlying cell envelope layer. The S-layer protein from B. stearothermophilus
      PV72/p6 has a molecular weight of 130,000 and assembles into a hexagonally
      ordered lattice. The S-layer from B. stearothermophilus ATCC 12980 shows oblique
      lattice symmetry and is composed of subunits with a molecular weight of 122,000.
      Immunoblotting, peptide mapping, N-terminal sequencing of the whole S-layer
      protein from B. stearothermophilus ATCC 12980 and of proteolytic cleavage
      fragments, and comparison with the S-layer protein from B. stearothermophilus
      PV72/p6 revealed that the two S-layer proteins have identical N-terminal regions
      but no other extended structurally homologous domains. In contrast to the
      heterogeneity observed for the S-layer proteins, the secondary cell wall polymer
      isolated from peptidoglycan-containing sacculi of the different strains showed
      identical chemical compositions and comparable molecular weights. The S-layer
      proteins could bind and recrystallize into the appropriate lattice type on native
      peptidoglycan-containing sacculi from both organisms but not on those extracted
      with hydrofluoric acid, leading to peptidoglycan of the A1gamma chemotype.
      Affinity studies showed that only proteolytic cleavage fragments possessing the
      complete N terminus of the mature S-layer proteins recognized native
      peptidoglycan-containing sacculi as binding sites or could associate with the
      isolated secondary cell wall polymer, while proteolytic cleavage fragments
      missing the N-terminal region remained unbound. From the results obtained in this
      study, it can be concluded that S-layer proteins from B. stearothermophilus wild
      type strains possess an identical N-terminal region which is responsible for
      anchoring the S-layer subunits to a secondary cell wall polymer of identical
      chemical composition.

PMID- 9515919
TI  - Role of the fnrL gene in photosystem gene expression and photosynthetic growth of
      Rhodobacter sphaeroides 2.4.1.
AB  - Anoxygenic photosynthetic growth of Rhodobacter sphaeroides 2.4.1 requires a
      functional fnrL gene, which encodes the anaerobic regulator, FnrL. Using
      transcriptional fusions to the puc operon in which the upstream FNR consensus
      like sequence is either present or absent, we obtained results that suggest that
      FnrL has both a direct and an indirect role in puc operon expression. In addition
      to FnrL, several other factors, including the two-component Prr regulatory system
      and the transcriptional repressor PpsR, are known to mediate oxygen control of
      photosynthesis gene expression in this organism. Therefore, we examined the
      relationship between FnrL and these other regulatory elements. Our results
      indicate that while mutations of prr or ppsR can lead to an increase in
      expression of some photosynthesis genes under aerobic and anaerobic conditions,
      regardless of the presence or absence of FnrL, there remains an absolute
      requirement for a functional fnrL gene for photosynthetic growth. We examined the
      potential role(s) of FnrL in photosynthetic growth by considering several target
      genes which may be required for this growth mode.

PMID- 9515920
TI  - The nif gene operon of the methanogenic archaeon Methanococcus maripaludis.
AB  - Nitrogen fixation occurs in two domains, Archaea and Bacteria. We have
      characterized a nif (nitrogen fixation) gene cluster in the methanogenic archaeon
      Methanococcus maripaludis. Sequence analysis revealed eight genes, six with
      sequence similarity to known nif genes and two with sequence similarity to glnB.
      The gene order, nifH, ORF105 (similar to glnB), ORF121 (similar to glnB), nifD,
      nifK, nifE, nifN, and nifX, was the same as that found in part in other
      diazotrophic methanogens and except for the presence of the glnB-like genes, also
      resembled the order found in many members of the Bacteria. Using transposon
      insertion mutagenesis, we determined that an 8-kb region required for nitrogen
      fixation corresponded to the nif gene cluster. Northern analysis revealed the
      presence of either a single 7.6-kb nif mRNA transcript or 10 smaller mRNA species
      containing portions of the large transcript. Polar effects of transposon
      insertions demonstrated that all of these mRNAs arose from a single promoter
      region, where transcription initiated 80 bp 5' to nifH. Distinctive features of
      the nif gene cluster include the presence of the six primary nif genes in a
      single operon, the placement of the two glnB-like genes within the cluster, the
      apparent physical separation of the cluster from any other nif genes that might
      be in the genome, the fragmentation pattern of the mRNA, and the regulation of
      expression by a repression mechanism described previously. Our study and others
      with methanogenic archaea reporting multiple mRNAs arising from gene clusters
      with only a single putative promoter sequence suggest that mRNA processing
      following transcription may be a common occurrence in methanogens.

PMID- 9515921
TI  - PcaU, a transcriptional activator of genes for protocatechuate utilization in
      Acinetobacter.
AB  - The Acinetobacter pcaIJFBDKCHG operon encodes the six enzymes that convert
      protocatechuate to citric acid cycle intermediates. Directly downstream from the
      operon are qui and pob genes encoding sets of enzymes that convert quinate and p
      hydroxybenzoate, respectively, to protocatechuate. Prior to this investigation,
      the only known regulatory gene in the pca-qui-pob cluster was pobR, which encodes
      a transcriptional activator that responds to p-hydroxybenzoate and activates
      transcription of pobA. The pca and qui genes were known to be expressed in
      response to protocatechuate, but a protein that mediated this induction had not
      been identified. This study was initiated by characterization of a spontaneous
      mutation that mapped upstream from pcaI and prevented expression of the pca
      genes. Sequencing of wild-type DNA extending from the translational start of pcaI
      through and beyond the location of the mutation revealed a 282-bp intergenic
      region and a divergently transcribed open reading frame, designated pcaU.
      Downstream from pcaU are two open reading frames encoding proteins similar in
      amino acid sequence to those associated with the oxidation of acyl thioesters.
      Inactivation of pcaU reduced the induced expression of pca structural genes by
      about 90% and impeded but did not completely prevent growth of the mutant cells
      with protocatechuate. PcaU was expressed in Escherichia coli and shown to bind to
      a portion of the pcaI-pcaU intergenic region containing a sequence identical in
      16 of 19 nucleotide residues to a segment of the pob operator. Further similarity
      of the two regulatory systems is indicated by 54% amino acid sequence identity in
      the aligned primary structures of PobR and PcaU. The pob and pca systems were
      shown to differ, however, in the relative orientations of transcriptional starts
      with respect to the site where the activator binds to DNA, the size of the
      intergenic region, and the tightness of transcriptional control. The spontaneous
      mutation blocking pca gene expression was located in the promoter for the pca
      operon. The 19-nucleotide residue operator sequences were shown to be parts of a
      consensus associated with transcriptional activation of genes associated with
      protocatechuate catabolism. Two different binding sites for Pseudomonas putida
      PcaR differ from the consensus in only a single nucleotide residue, and DNA
      directly downstream from Acinetobacter pcaU contains a 19-bp segment differing
      from the consensus in only two residues. PcaU was shown to bind to DNA containing
      this segment as well as to the DNA in the pcaU-pcaI intergenic region.

PMID- 9515922
TI  - Activation of Escherichia coli rRNA transcription by FIS during a growth cycle.
AB  - rRNA transcription in Escherichia coli is activated by the FIS protein, which
      binds upstream of rrnp1 promoters and interacts directly with RNA polymerase.
      Analysis of the contribution of FIS to rrn transcription under changing
      physiological conditions is complicated by several factors: the wide variation in
      cellular FIS concentrations with growth conditions, the contributions of several
      other regulatory systems to rRNA synthesis, and the pleiotropy of fis mutations.
      In this report, we show by in vivo footprinting and Western blot analysis that
      occupancy of the rrnBp1 FIS sites correlates with cellular levels of FIS. We
      find, using two methods of measurement (pulse induction of a FIS-activated hybrid
      promoter and primer extension from an unstable transcript made from rrnBp1), that
      the extent of transcription activation by FIS parallels the degree of FIS site
      occupancy and therefore cellular FIS levels. FIS activates transcription
      throughout exponential growth at low culture density, but rrnp1 transcription
      increases independently of FIS immediately following upshift, before FIS
      accumulates. These results support the model that FIS is one of a set of
      overlapping signals that together contribute to transcription from rrnp1
      promoters during steady-state growth.

PMID- 9515923
TI  - Characterization of the gene cassette required for biosynthesis of the (alpha1-
      >6)-linked N-acetyl-D-mannosamine-1-phosphate capsule of serogroup A Neisseria
      meningitidis.
AB  - The (alpha1-->6)-linked N-acetyl-D-mannosamine-1-phosphate meningococcal capsule
      of serogroup A Neisseria meningitidis is biochemically distinct from the sialic
      acid-containing capsules produced by other disease-associated meningococcal
      serogroups (e.g., B, C, Y, and W-135). We defined the genetic cassette
      responsible for expression of the serogroup A capsule. The cassette comprised a
      4,701-bp nucleotide sequence located between the outer membrane capsule
      transporter gene, ctrA, and galE, encoding the UDP-glucose-4-epimerase. Four open
      reading frames (ORFs) not found in the genomes of the other meningococcal
      serogroups were identified. The first serogroup A ORF was separated from ctrA by
      a 218-bp intergenic region. Reverse transcriptase (RT) PCR and primer extension
      studies of serogroup A mRNA showed that all four ORFs were cotranscribed in the
      opposite orientation to ctrA and that transcription of the ORFs was initiated
      from the intergenic region by a sigma-70-type promoter that overlapped the ctrA
      promoter. The first ORF exhibited 58% amino acid identity with the UDP-N-acetyl-D
      glucosamine (UDP-GlcNAc) 2-epimerase of Escherichia coli, which is responsible
      for the conversion of UDP-GlcNAc into UDP-N-acetyl-D-mannosamine. Polar or
      nonpolar mutagenesis of each of the ORFs resulted in an abrogation of serogroup A
      capsule production as determined by colony immunoblots and enzyme-linked
      immunosorbent assay. Replacement of the serogroup A biosynthetic gene cassette
      with a serogroup B cassette by transformation resulted in capsule switching from
      a serogroup A capsule to a serogroup B capsule. These data indicate that assembly
      of the serogroup A capsule likely begins with monomeric UDP-GlcNAc and requires
      proteins encoded by three other genes found in the serogroup A N. meningitidis
      specific operon located between ctrA and galE.

PMID- 9515925
TI  - The bldD gene of Streptomyces coelicolor A3(2): a regulatory gene involved in
      morphogenesis and antibiotic production.
AB  - The bld mutants of Streptomyces coelicolor A3(2) are blocked at the earliest
      stage of sporulation, the formation of aerial hyphae, and are pleiotropically
      defective in antibiotic production. Using a phage library of wild-type S.
      coelicolor DNA, we isolated a recombinant phage which restored both sporulation
      and antibiotic production to strains carrying the single known bldD mutation.
      Nucleotide sequence analysis of a 1.3-kb complementing subclone identified an
      open reading frame, designated bldD, encoding a translation product of 167 amino
      acid residues. Nucleotide sequence analysis of the bldD-containing fragment
      amplified from the chromosome of a bldD mutant strain revealed a point mutation
      changing a tyrosine residue at amino acid position 62 to a cysteine. Although a
      comparison of the BldD sequence to known proteins in the databases failed to show
      any strong similarities, analysis of the BldD sequence for secondary structural
      elements did reveal a putative helix-turn-helix, DNA recognition element near the
      C terminus of the protein. A comparison of bldD transcript levels in the bldD+
      and bldD mutant strains using both Northern blot analysis and S1 nuclease
      protection studies showed vast overexpression of bldD transcripts in the mutant,
      suggesting that BldD negatively regulates its own synthesis. High-resolution S1
      nuclease mapping identified the transcription start point as a G residue 63
      nucleotides upstream from the bldD start codon and 7 nucleotides downstream from 
      10 and -35 sequences resembling E. coli-like streptomycete promoters.

PMID- 9515924
TI  - Purification of the pyruvate dehydrogenase multienzyme complex of Zymomonas
      mobilis and identification and sequence analysis of the corresponding genes.
AB  - The pyruvate dehydrogenase (PDH) complex of the gram-negative bacterium Zymomonas
      mobilis was purified to homogeneity. From 250 g of cells, we isolated 1 mg of PDH
      complex with a specific activity of 12.6 U/mg of protein. Analysis of subunit
      composition revealed a PDH (E1) consisting of the two subunits E1alpha (38 kDa)
      and E1beta (56 kDa), a dihydrolipoamide acetyltransferase (E2) of 48 kDa, and a
      lipoamide dehydrogenase (E3) of 50 kDa. The E2 core of the complex is arranged to
      form a pentagonal dodecahedron, as shown by electron microscopic images,
      resembling the quaternary structures of PDH complexes from gram-positive bacteria
      and eukaryotes. The PDH complex-encoding genes were identified by hybridization
      experiments and sequence analysis in two separate gene regions in the genome of
      Z. mobilis. The genes pdhAalpha (1,065 bp) and pdhAbeta (1,389 bp), encoding the
      E1alpha and E1beta subunits of the E1 component, were located downstream of the
      gene encoding enolase. The pdhB (1,323 bp) and lpd (1,401 bp) genes, encoding the
      E2 and E3 components, were identified in an unrelated gene region together with a
      450-bp open reading frame (ORF) of unknown function in the order pdhB-ORF2-lpd.
      Highest similarities of the gene products of the pdhAalpha, pdhAbeta, and pdhB
      genes were found with the corresponding enzymes of Saccharomyces cerevisiae and
      other eukaryotes. Like the dihydrolipoamide acetyltransferases of S. cerevisiae
      and numerous other organisms, the product of the pdhB gene contains a single
      lipoyl domain. The E1beta subunit PDH was found to contain an amino-terminal
      lipoyl domain, a property which is unique among PDHs.

PMID- 9515927
TI  - In vivo protein interactions within the Escherichia coli DNA polymerase III core.
AB  - The mechanisms that control the fidelity of DNA replication are being
      investigated by a number of approaches, including detailed kinetic and structural
      studies. Important tools in these studies are mutant versions of DNA polymerases
      that affect the fidelity of DNA replication. It has been suggested that proper
      interactions within the core of DNA polymerase III (Pol III) of Escherichia coli
      could be essential for maintaining the optimal fidelity of DNA replication (H.
      Maki and A. Kornberg, Proc. Natl. Acad. Sci. USA 84:4389-4392, 1987). We have
      been particularly interested in elucidating the physiological role of the
      interactions between the DnaE (alpha subunit [possessing DNA polymerase
      activity]) and DnaQ (epsilon subunit [possessing 3'-->5' exonucleolytic
      proofreading activity]) proteins. In an attempt to achieve this goal, we have
      used the Saccharomyces cerevisiae two-hybrid system to analyze specific in vivo
      protein interactions. In this report, we demonstrate interactions between the
      DnaE and DnaQ proteins and between the DnaQ and HolE (theta subunit) proteins. We
      also tested the interactions of the wild-type DnaE and HolE proteins with three
      well-known mutant forms of DnaQ (MutD5, DnaQ926, and DnaQ49), each of which leads
      to a strong mutator phenotype. Our results show that the mutD5 and dnaQ926
      mutations do not affect the epsilon subunit-alpha subunit and epsilon subunit
      theta subunit interactions. However, the dnaQ49 mutation greatly reduces the
      strength of interaction of the epsilon subunit with both the alpha and the theta
      subunits. Thus, the mutator phenotype of dnaQ49 may be the result of an altered
      conformation of the epsilon protein, which leads to altered interactions within
      the Pol III core.

PMID- 9515926
TI  - The bldB gene encodes a small protein required for morphogenesis, antibiotic
      production, and catabolite control in Streptomyces coelicolor.
AB  - Mutants blocked at the earliest stage of morphological development in
      Streptomyces species are called bld mutants. These mutants are pleiotropically
      defective in the initiation of development, the ability to produce antibiotics,
      the ability to regulate carbon utilization, and the ability to send and/or
      respond to extracellular signals. Here we report the identification and partial
      characterization of a 99-amino-acid open reading frame (ORF99) that is capable of
      restoring morphogenesis, antibiotic production, and catabolite control to all of
      the bldB mutants. Of the existing bld mutants, bldB is of special interest
      because the phenotype of this mutant is the most pleiotropic. DNA sequence
      analysis of ORF99 from each of the existing bldB mutants identified base changes
      either within the coding region of the predicted protein or in the regulatory
      region of the gene. Primer extension analysis identified an apparent
      transcription start site. A promoter fusion to the xylE reporter gene showed that
      expression of bldB is apparently temporally regulated and that the bldB gene
      product is involved in the regulation of its own expression.

PMID- 9515930
TI  - Lambda Xis degradation in vivo by Lon and FtsH.
AB  - Lambda Xis, which is required for site-specific excision of phage lambda from the
      bacterial chromosome, has a much shorter functional half-life than Int, which is
      required for both integration and excision (R. A. Weisberg and M. E. Gottesman,
      p. 489-500, in A. D. Hershey, ed., The Bacteriophage Lambda, 1971). We found that
      Xis is degraded in vivo by two ATP-dependent proteases, Lon and FtsH (HflB). Xis
      was stabilized two- to threefold more than in the wild type in a lon mutant and
      as much as sixfold more in a lon ftsH double mutant at the nonpermissive
      temperature for the ftsH mutation. Integration of lambda into the bacterial
      chromosome was delayed in the lon ftsH background, suggesting that accumulation
      of Xis in vivo interferes with integration. Overexpression of Xis in wild-type
      cells from a multicopy plasmid inhibited integration of lambda and promoted
      curing of established lysogens, confirming that accumulation of Xis interferes
      with the ability of Int to establish and maintain an integrated prophage.

PMID- 9515928
TI  - Hybrid Bordetella pertussis-Escherichia coli RNA polymerases: selectivity of
      promoter activation.
AB  - We constructed hybrid Bordetella pertussis-Escherichia coli RNA polymerases and
      compared productive interactions between transcription activators and cognate RNA
      polymerase subunits in an in vitro transcription system. Virulence-associated
      genes of B. pertussis, in the presence of their activator BvgA, are transcribed
      by all variants of hybrid RNA polymerases, whereas transcription at the E. coli
      lac promoter regulated by the cyclic AMP-catabolite gene activator protein has an
      absolute requirement for the E. coli alpha subunit. This suggests that activator
      contact sites involve a high degree of selectivity.

PMID- 9515929
TI  - Melanin biosynthesis in Cryptococcus neoformans.
AB  - Pigment production by Cryptococcus neoformans is virulence associated. Dopamine-
      and 3,4-dihydroxyphenylalanine-melanin products were identified after acidic
      permanganate oxidation, alkaline hydrogen peroxide oxidation, or hydrolysis with
      hydriodic acid. These data provide direct chemical evidence for the formation of
      eumelanin polymers by catecholamine oxidation by laccase alone followed by
      oxidative coupling of dihydroxyindole.

PMID- 9515931
TI  - Molecular cloning, expression, and characterization of the genes encoding the two
      essential protein components of Micrococcus luteus B-P 26 hexaprenyl diphosphate
      synthase.
AB  - The structural genes encoding the two essential components A and B of hexaprenyl
      diphosphate synthase, which produce the precursor of the prenyl side chain of
      menaquinone-6, were cloned from Micrococcus luteus B-P 26.

PMID- 9515932
TI  - Isolation and purification of two novel streptomycete RNase inhibitors, SaI14 and
      SaI20, and cloning, sequencing, and expression in Escherichia coli of the gene
      coding for SaI14.
AB  - Two new RNase inhibitors, SaI14 (Mr, approximately 14,000) and SaI20 (Mr,
      approximately 20,000), were isolated and purified from a Streptomyces
      aureofaciens strain. The gene sai14, coding for SaI14 protein, was cloned and
      expressed in Escherichia coli. The alignment of the deduced amino acid sequence
      of SaI14 with that of barstar, the RNase inhibitor from Bacillus
      amyloliquefaciens, showed significant similarity between them, especially in the
      region which contains most of the residues involved in barnase-barstar complex
      formation.

PMID- 9515933
TI  - The folate branch of the methionine biosynthesis pathway in Streptomyces
      lividans: disruption of the 5,10-methylenetetrahydrofolate reductase gene leads
      to methionine auxotrophy.
AB  - In enterobacteria, the methyl group of methionine is donated by 5
      methyltetrahydrofolate that is synthesized from N5,10-methylenetetrahydrofolate
      by the 5,10-methylenetetrahydrofolate reductase. The Streptomyces lividans metF
      gene, which encodes 5,10-methylenetetrahydrofolate reductase, has been cloned. It
      encodes a protein of 307 amino acids with a deduced molecular mass of 33,271 Da.
      S1 exonuclease mapping of the transcription initiation site showed that the metF
      gene is expressed, forming a leaderless mRNA. A 13-bp tandem repeat located
      immediately upstream of the promoter region shows homology with the consensus
      MetR-binding sequence of Salmonella typhimurium. Expression of metF in multicopy
      plasmids in S. lividans resulted in accumulation of a 32-kDa protein, as shown by
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Disruption of the metF
      gene led to methionine auxotrophy. Integration of the disrupting plasmid at the
      metF locus was confirmed by Southern hybridization in three randomly isolated
      transformants. The methionine auxotrophy was complemented by transformation of
      the auxotrophs with an undisrupted metF gene. These results indicate that the
      folate branch is essential for methionine biosynthesis in streptomycetes, as
      occurs in enterobacteria.

PMID- 9515934
TI  - Identification and characterization of a novel competence gene, comC, required
      for DNA binding and uptake in Acinetobacter sp. strain BD413.
AB  - A gene (comC) essential for natural transformation was identified in
      Acinetobacter sp. strain BD413. ComC has a typical leader sequence and is similar
      to different type IV pilus assembly factors. A comC mutant (T308) is not able to
      bind or take up DNA but exhibits a piliation phenotype indistinguishable from the
      transformation wild type as revealed by electron microscopy.

PMID- 9515935
TI  - Cloning and sequencing of a form II ribulose-1,5-biphosphate
      carboxylase/oxygenase from the bacterial symbiont of the hydrothermal vent
      tubeworm Riftia pachyptila.
AB  - The bacterial symbiont of the hydrothermal vent tubeworm fixes carbon via the
      Calvin-Benson cycle and has been shown previously to express a form II ribulose
      1,5-bisphosphate carboxylase/oxygenase (RubisCO). The gene cbbM, which encodes
      this enzyme, has been cloned and sequenced. The gene has the highest identity
      with the cbbM gene from Rhodospirillum rubrum, and analysis of the inferred amino
      acid sequence reveals that all active-site residues are conserved. This is the
      first form II RubisCO cloned and sequenced from a chemoautotrophic symbiont and
      from a deep-sea organism.

PMID- 9515936
TI  - Sensory rhodopsin II transducer HtrII is also responsible for serine chemotaxis
      in the archaeon Halobacterium salinarum.
AB  - Previously, we demonstrated that the methyl-accepting protein HtrII is the
      transducer for photoreceptor sensory rhodopsin II. Here, we provide experimental
      evidence that HtrII is also a chemotransducer. Using an agarose-in-plug bridge
      method, we show that an HtrII overexpression strain has a quicker response to
      serine than does an HtrII deletion strain. Furthermore, an in vivo flow assay
      demonstrates that the deletion strain is unable to modulate methylesterase
      activity after serine addition or photostimulation, while the overexpression
      strain shows distinct methanol peaks following both types of stimuli.

PMID- 9515937
TI  - Trehalose is not relevant for in vivo activity of sigmaS-containing RNA
      polymerase in Escherichia coli.
AB  - The sigmaS- and sigma70-associated forms of RNA polymerase core enzyme (E) of
      Escherichia coli have very similar promoter recognition specificities in vitro.
      Nevertheless, the in vivo expression of many stress response genes is strongly
      dependent on sigmaS. Based on in vitro assays, it has recently been proposed that
      the disaccharide trehalose specifically stimulates the formation and activity of
      EsigmaS and thereby contributes to promoter selectivity (S. Kusano and A.
      Ishihama, J. Bacteriol. 179:3649-3654, 1997). However, we demonstrate here that a
      trehalose-free otsA mutant exhibits growth phase-related and osmotic induction of
      various sigmaS-dependent genes which is indistinguishable from that of an
      otherwise isogenic wild-type strain and that stationary-phase cells do not
      accumulate trehalose (even though the trehalose-synthesizing enzymes are
      induced). We conclude that in vivo trehalose does not play a role in the
      expression of sigmaS-dependent genes and therefore also not in sigma factor
      selectivity at the promoters of these genes.

PMID- 9515938
TI  - Arsenate toxicity in human erythrocytes: characterization of morphologic changes
      and determination of the mechanism of damage.
AB  - Chronic arsenic exposure is associated with alterations in peripheral circulation
      and vascular disease. Toxicity to the vasculature is documented, but the effect
      of arsenic on the erythrocyte has not been evaluated. To determine if arsenic was
      toxic to human erythrocytes and whether this could contribute to vascular
      disease, human erythrocytes were incubated in vitro with sodium arsenate, As(V),
      or sodium arsenite, As(III), and assessed for damage. After 5 h of incubation
      with 10 mM As(V) or As(III), significant cell death (hemolysis) only occurred in
      the As(V) treated cells. Morphologic changes were assessed by scanning electron
      microscopy and light microscopy. As(V) induced a classic discocyte-echinocyte
      transformation extending to the formation of sphero-echinocytes; these changes
      were concentration dependent. As(III) treatment also resulted in echinocyte
      formation but less extensive than in As(V) treated cells, and no sphero
      echinocytes were formed. The observed damage was consistent with reported changes
      induced by ATP depletion, and measurement of ATP in these samples confirmed this
      as a mechanism of damage. As(V) treatment at concentrations as low as 0.01 mM for
      5 h significantly depleted ATP, and As(III) was relatively ineffective in causing
      ATP depletion. Based on these three parameters, the erythrocyte was estimated to
      be as much as 1000 times more susceptible to As(V) than As(III). ATP is required
      for the cell to maintain membrane integrity and deform efficiently in
      circulation. The changes described here could contribute to vascular occlusion,
      ischemia, and tissue death associated with arsenic circulatory disorders.

PMID- 9515939
TI  - Differential production of interleukin-6 in the brain and spleen of mice treated
      with lipopolysaccharide in the presence and absence of lead.
AB  - The heavy metal lead (Pb) markedly augments the lethality of endotoxin in
      laboratory animals. Much of the tissue injury produced by endotoxin is thought to
      be mediated by cytokines. Thus, the effects of Pb on the regulation of
      interleukin-6 (IL-6), a proinflammatory cytokine that shows high correlation with
      symptoms of endotoxic shock, and the levels of corticosterone, a hormone produced
      to prepare the body to cope with stress, upon lipopolysaccharide (LPS; endotoxin)
      administration were investigated. After intravenous administration of LPS, the
      kinetics of IL-6 gene expression by Northern blot analysis revealed a rapid
      increase of IL-6 mRNA, which peaked by 2 h in the spleens and 3 h in the brains
      of B6C3F1 female mice, with or without Pb exposure. Peak production of IL-6
      protein after LPS challenge was observed at 2 h in the spleens and 3 h in the
      sera regardless of Pb-treatment. However, Pb-exposed mice showed an altered
      kinetic profile of IL-6 appearance in the brain, in that the levels of IL-6 in
      the brains peaked at 4 h rather than 3 h, the peak for the control mice.
      Moreover, at two time points, the amounts of IL-6 were found to be higher in the
      brains of Pb-treated mice. Increases in IL-6 were detected in multiple areas of
      the brain, but Pb did not significantly enhance this level in any area. The
      observation of both IL-6 transcripts and protein in the brains of mice upon
      peripheral LPS administration is indicative of local de novo synthesis of IL-6 in
      the brain. IL-6 production in the brain may contribute to the centrally mediated
      effects of IL-6, since IL-6 in the brain is known to activate the hypothalamus
      pituitary-adrenal (HPA) axis. Upon LPS challenge, corticosterone levels peaked at
      the 2-h time point and stayed elevated for 6 h regardless of Pb exposure. The
      increases in brain IL-6 and its extended expression by Pb do not appear to have
      significantly altered the HPA axis on the basis of the corticosterone level, but
      brain IL-6 is known to affect multiple brain functions such as long-term
      potentiation.

PMID- 9515940
TI  - Effect of dietary chlorogenic acid on multiple immune functions and formation of
      aberrant crypt foci in rats.
AB  - Adult male Sprague-Dawley rats were fed 70 mg/kg body weight chlorogenic acid
      (CHA) for 7 wk. One CHA-fed group was also given 2 injections of the colon
      carcinogen azoxymethane (AZO) on d 2 and 9 of CHA treatment. Three major types of
      immune responses were assessed: antibody production, specific cell-mediated
      immunity, and nonspecific cell-mediated immunity. The formation of AZO-induced
      aberrant crypt foci (ACF) in the colon were observed, as was colonic cell
      proliferation. There were no significant effects of CHA treatment on any of the
      immune parameters examined or on formation of preneoplastic lesions or cell
      proliferation in the colon. The overall nonsignificant trends in immune function,
      colon cell proliferation, and ACF development were, however, more consistent with
      immunosuppression and enhanced preneoplasia.

PMID- 9515941
TI  - Inhibition of carboxylesterases in SH-SY5Y human and NB41A3 mouse neuroblastoma
      cells by organophosphorus esters.
AB  - Carboxylesterases (CbxE) can be inhibited by organophosphorus esters (OPs)
      without causing clinical evidence of toxicity. CbxE are thought to protect the
      critical enzyme acetylcholinesterase (AChE) from OP inhibition in animals. CbxE
      and AChE are both present in neuroblastoma cells, but, even though these cells
      have potential to be an in vitro model of OP toxicity, the effect of OPs on CbxE
      and the relationship of CbxE inhibition and AChE inhibition have not yet been
      examined in these cells. Therefore, this study examined concentration-related OP
      induced inhibition of CbxE in human SH-SY5Y and mouse NB41A3 neuroblastoma cells
      with 11 active esterase inhibitors: paraoxon, malaoxon, chlorpyrifos-oxon, tolyl
      saligenin phosphate (TSP), phenyl saligenin phosphate (PSP), diisopropyl
      phosphorofluoridate (DFP), mipafox, dichlorvos, trichlorfon, dibutyryl
      dichlorovinyl phosphate (DBVP), and dioctyl dichlorovinyl phosphate (DOVP). All
      could inhibit CbxE, although the enzyme was less likely to be inhibited than AChE
      following exposure to 9 of the test compounds in the human cell line and to all
      11 of the test compounds in the murine cell line. Species differences in
      concentration-related inhibitions of CbxE were evident. When cells were exposed
      first to an OP with a low IC50 toward CbxE (PSP), followed by an OP with high
      affinity for AChE (paraoxon or malaoxon), inhibitions of CbxE and AChE were
      additive. This indicated that CbxE did not protect AChE from OP-induced
      inhibition in this cell culture model.

PMID- 9515942
TI  - Acceleration of mammary tumorigenesis by exposure of 7,12
      dimethylbenz[a]anthracene-treated female rats in a 50-Hz, 100-microT magnetic
      field: replication study.
AB  - In view of the methodological problems of epidemiological studies on associations
      between residential and occupational exposures to 50/60-Hz magnetic fields (MF)
      and increased incidence of cancers, laboratory studies are necessary to determine
      if 50/60-Hz MF can affect cancer development or growth. Recently, it was reported
      that alternating (50-Hz) MF of low flux density (100 microT) increase tumor
      growth and progression in a model of breast cancer in female rats in which
      mammary tumors were induced by the chemical carcinogen 7,12
      dimethylbenz[a]anthracene (DMBA). The objective of the present study was to
      determine if a replicate experiment carried out in the same laboratory under the
      same experimental conditions yields a significant increase in tumor development
      and growth of similar magnitude. For the MF experiment, a group of 99 female
      Sprague-Dawley rats was exposed to a homogeneous horizontally polarized MF for 24
      h/d (minus time for weighing, tumor palpation, cage cleaning, cage rotation), 7
      d/wk; another group of 99 rats was sham exposed. DMBA was administered
      intragastrically at a dose of 5 mg/rat at the first day of exposure and at weekly
      intervals thereafter up to a total dose of 20 mg/rat. Duration of MF or sham
      exposure was 91 d. In both MF-exposed and sham-exposed rats, the first tumors
      could be recorded 6 wk after the initial DMBA application. At 9 wk after DMBA
      application, the group of MF-exposed rats exhibited significantly more animals
      with tumors than the sham-exposed group. This significant difference in the rate
      of tumor development was observed throughout the subsequent period of exposure.
      After autopsy, the incidence of macroscopically visible mammary tumors was 62% in
      controls, but 83% in MF-exposed rats, with the 35% difference between groups
      being statistically significant. Data substantiate that long-term exposure of
      DMBA-treated female Sprague-Dawley rats in an alternating MF of low flux density
      promotes the development and growth of mammary tumors, thus indicating that MF
      exposure exerts tumor-promoting and/or copromoting effects. Furthermore, the data
      show that the effects of MF exposure in the DMBA breast cancer model are
      reproducible if the same experiment is repeated in the same laboratory.

PMID- 9515943
TI  - Opportunity for depth in Chinese eugenics debate.

PMID- 9515944
TI  - Ice on the Moon boosts hopes for future lunar missions.

PMID- 9515945
TI  - French clone provides support for Dolly.

PMID- 9515946
TI  - Congressman launches plagiarism inquiry.

PMID- 9515947
TI  - NIH's way of setting priorities endorsed.

PMID- 9515948
TI  - Australia reviews medical research funding.

PMID- 9515949
TI  - Bid to block Yellowstone enzymes deal.

PMID- 9515950
TI  - Plan for $100m boost to Israeli biotech comes under threat.

PMID- 9515951
TI  - Glaxo cuts HIV drug cost for developing world.

PMID- 9515952
TI  - Addiction, the tobacco industry and Nature.

PMID- 9515953
TI  - Human pheromones. Communication through body odour.

PMID- 9515954
TI  - Cardiac development. Transcription and the broken heart.

PMID- 9515955
TI  - A cold break for photoreceptors.

PMID- 9515956
TI  - Meteoritics. Diamonds in the dust.

PMID- 9515957
TI  - Membrane sorting. Endosome marker is fat not fiction.

PMID- 9515958
TI  - GroE is vital for cell-wall synthesis.

PMID- 9515959
TI  - Alzheimer's peptide kills cells of retina in vivo.

PMID- 9515960
TI  - Are retrotransposons long-term hitchhikers?

PMID- 9515961
TI  - Regulation of ovulation by human pheromones.
AB  - Pheromones are airborne chemical signals that are released by an individual into
      the environment and which affect the physiology or behaviour of other members of
      the same species. The idea that humans produce pheromones has excited the
      imagination of scientists and the public, leading to widespread claims for their
      existence, which, however, has remained unproven. Here we investigate whether
      humans produce compounds that regulate a specific neuroendocrine mechanism in
      other people without being consciously detected as odours (thereby fulfilling the
      classic definition of a pheromone). We found that odourless compounds from the
      armpits of women in the late follicular phase of their menstrual cycles
      accelerated the preovulatory surge of luteinizing hormone of recipient women and
      shortened their menstrual cycles. Axillary (underarm) compounds from the same
      donors which were collected later in the menstrual cycle (at ovulation) had the
      opposite effect: they delayed the luteinizing-hormone surge of the recipients and
      lengthened their menstrual cycles. By showing in a fully controlled experiment
      that the timing of ovulation can be manipulated, this study provides definitive
      evidence of human pheromones.

PMID- 9515962
TI  - Motor role of human inferior parietal lobe revealed in unilateral neglect
      patients.
AB  - The exact role of the parietal lobe in spatial cognition is controversial. One
      influential hypothesis proposes that it subserves spatial perception, whereas
      other accounts suggest that its primary role is to direct spatial movement. For
      humans, it has been suggested that these functions may be divided between
      inferior and superior parietal lobes, respectively. In apparent support of a
      purely perceptual function for the inferior parietal lobe (IPL), patients with
      lesions to this structure, particularly in the right hemisphere, exhibit
      unilateral spatial neglect (deficient awareness for the side of space opposite to
      that of their lesion). Here we show that patients with right IPL lesions also
      have a specific difficulty in initiating leftward movements towards visual
      targets on the left side of space. This motor impairment was not found in neglect
      patients with frontal lesions, contrary to previous proposals that motor aspects
      of neglect are particularly associated with anterior damage. Our results suggest
      that the human IPL operates as a sensorimotor interface, rather than subserving
      only perceptual functions.

PMID- 9515963
TI  - Role of the NF-ATc transcription factor in morphogenesis of cardiac valves and
      septum.
AB  - In lymphocytes, the expression of early immune response genes is regulated by NF
      AT transcription factors which translocate to the nucleus after dephosphorylation
      by the Ca2+-dependent phosphatase, calcineurin. We report here that mice bearing
      a disruption in the NF-ATc gene fail to develop normal cardiac valves and septa
      and die of circulatory failure before day 14.5 of development. NF-ATc is first
      expressed in the heart at day 7.5, and is restricted to the endocardium, a
      specialized endothelium that gives rise to the valves and septum. Within the
      endocardium, specific inductive events appear to activate NF-ATc: it is localized
      to the nucleus only in endocardial cells that are adjacent to the interface with
      the cardiac jelly and myocardium, which are thought to give the inductive
      stimulus to the valve primordia. Treatment of wild-type embryos with FK506, a
      specific calcineurin inhibitor, prevents nuclear localization of NF-ATc. These
      data indicate that the Ca2+/calcineurin/NF-ATc signalling pathway is essential
      for normal cardiac valve and septum morphogenesis; hence, NF-ATc and its
      regulatory pathways are candidates for genetic defects underlying congenital
      human heart disease.

PMID- 9515964
TI  - The transcription factor NF-ATc is essential for cardiac valve formation.
AB  - Nuclear factor of activated T cells (NF-AT) is the name of a family of four
      related transcription factors that may be needed for cytokine gene expression in
      activated lymphocytes. Here we report that mice with a targeted disruption of the
      NF-ATc gene show an unexpected and dramatic defect in cardiac morphogenesis, with
      selective absence of the aortic and pulmonary valves, leading to death in utero
      from congestive heart failure at days 13.5-17.5 of gestation. In contrast,
      tricuspid and mitral valve morphogenesis is normal. NF-ATc is the first
      transcription factor known to be expressed only in the endothelial cells of the
      heart. As in T cells, nuclear translocation of NF-ATc in cardiac endothelial
      cells is controlled by the calcium-regulated phosphatase calcineurin: NF-ATc
      remains cytoplasmic in normal embryos cultured with cyclosporin A, an inhibitor
      of calcineurin. Abnormal development of the cardiac valves and septae is the most
      frequent form of birth defect, yet few molecular regulators of valve formation
      are known. Our results indicate that NF-ATc may play a critical role in signal
      transduction processes required for normal cardiac valve formation.

PMID- 9515965
TI  - A causal role for E-cadherin in the transition from adenoma to carcinoma.
AB  - Development of malignant tumours is in part characterized by the ability of a
      tumour cell to overcome cell-cell adhesion and to invade surrounding tissue. E
      cadherin is the main adhesion molecule of epithelia, and it has been implicated
      in carcinogenesis because it is frequently lost in human epithelial cancers. Re
      establishing the functional cadherin complex in tumour cell lines results in a
      reversion from an invasive to a benign epithelial phenotype. However, it remained
      unresolved whether the loss of E-cadherin-mediated cell adhesion was a cause or a
      consequence of tumour progression in vivo. Here we report that the loss of E
      cadherin expression coincides with the transition from well differentiated
      adenoma to invasive carcinoma in a transgenic mouse model of pancreatic beta-cell
      carcinogenesis (Rip1Tag2). Intercrossing Rip1Tag2 mice with transgenic mice that
      maintain E-cadherin expression in beta-tumour cells results in arrest of tumour
      development at the adenoma stage, whereas expression of a dominant-negative form
      of E-cadherin induces early invasion and metastasis. The results demonstrate that
      loss of E-cadherin-mediated cell adhesion is one rate-limiting step in the
      progression from adenoma to carcinoma.

PMID- 9515966
TI  - A lipid associated with the antiphospholipid syndrome regulates endosome
      structure and function.
AB  - Little is known about the structure and function of membrane domains in the
      vacuolar apparatus of animal cells. A unique feature of late endosomes, which are
      part of the pathway that leads to lysosomes, is that they contain a complex
      system of poorly characterized internal membranes in their lumen. These endosomes
      are therefore known as multivesicular or multilamellar organelles. Some proteins
      distribute preferentially within these internal membranes, whereas others are
      exclusively localized to the organelle's limiting membrane. The composition and
      function of this membrane system are poorly understood. Here we show that these
      internal membranes contain large amounts of a unique lipid, and thus form
      specialized domains within endosomes. These specialized domains are involved in
      sorting the multifunctional receptor for insulin-like growth factor 2 and ligands
      bearing mannose-6-phosphate, in particular lysosomal enzymes. We also show that
      this unique lipid is a specific antigen for human antibodies associated with the
      antiphospholipid syndrome. These antibodies may act intracellularly by altering
      the protein-sorting functions of endosomes.

PMID- 9515967
TI  - Translocation of calmodulin to the nucleus supports CREB phosphorylation in
      hippocampal neurons.
AB  - Activation of the transcription factor CREB is thought to be important in the
      formation of long-term memory in several animal species. The phosphorylation of a
      serine residue at position 133 of CREB is critical for activation of CREB. This
      phosphorylation is rapid when driven by brief synaptic activity in hippocampal
      neurons. It is initiated by a highly local, rise in calcium ion concentrations
      near the cell membrane, but culminates in the activation of a specific calmodulin
      dependent kinase known as CaMK IV, which is constitutively present in the
      neuronal nucleus. It is unclear how the signal is conveyed from the synapse to
      the nucleus. We show here that brief bursts of activity cause a swift
      (approximately 1 min) translocation of calmodulin from the cytoplasm to the
      nucleus, and that this translocation is important for the rapid phosphorylation
      of CREB. Certain Ca2+ entry systems (L-type Ca2+ channels and NMDA receptors) are
      able to cause mobilization of calmodulin, whereas others (N- and P/Q-type Ca2+
      channels) are not. This translocation of calmodulin provides a form of cellular
      communication that combines the specificity of local Ca2+ signalling with the
      ability to produce action at a distance.

PMID- 9515968
TI  - The hyperthermophile chromosomal protein Sac7d sharply kinks DNA.
AB  - The proteins Sac7d and Sso7d belong to a class of small chromosomal proteins from
      the hyperthermophilic archaeon Sulfolobus acidocaldarius and S. solfactaricus,
      respectively. These proteins are extremely stable to heat, acid and chemical
      agents. Sac7d binds to DNA without any particular sequence preference and thereby
      increases its melting temperature by approximately 40 degrees C. We have now
      solved and refined the crystal structure of Sac7d in complex with two DNA
      sequences to high resolution. The structures are examples of a nonspecific DNA
      binding protein bound to DNA, and reveal that Sac7d binds in the minor groove,
      causing a sharp kinking of the DNA helix that is more marked than that induced by
      any sequence-specific DNA-binding proteins. The kink results from the
      intercalation of specific hydrophobic side chains of Sac7d into the DNA
      structure, but without causing any significant distortion of the protein
      structure relative to the uncomplexed protein in solution.

PMID- 9515970
TI  - Are two antidepressant mechanisms better than one?

PMID- 9515969
TI  - Structure at 0.85 A resolution of an early protein photocycle intermediate.
AB  - Protein photosensors from all kingdoms of life use bound organic molecules, known
      as chromophores, to detect light. A specific double bond within each chromophore
      is isomerized by light, triggering slower changes in the protein as a whole. The
      initial movements of the chromophore, which can occur in femtoseconds, are
      tightly constrained by the surrounding protein, making it difficult to see how
      isomerization can occur, be recognized, and be appropriately converted into a
      protein-wide structural change and biological signal. Here we report how this
      dilemma is resolved in the photoactive yellow protein (PYP). We trapped a key
      early intermediate in the light cycle of PYP at temperatures below -100 degrees
      C, and determined its structure at better than 1 A resolution. The 4
      hydroxycinnamoyl chromophore isomerizes by flipping its thioester linkage with
      the protein, thus avoiding collisions resulting from large-scale movement of its
      aromatic ring during the initial light reaction. A protein-to-chromophore
      hydrogen bond that is present in both the preceding dark state and the subsequent
      signalling state of the photosensor breaks, forcing one of the hydrogen-bonding
      partners into a hydrophobic pocket. The isomerized bond is distorted into a
      conformation resembling that in the transition state. The resultant stored energy
      is used to drive the PYP light cycle. These results suggest a model for
      phototransduction, with implications for bacteriorhodopsin, photoactive proteins,
      PAS domains, and signalling proteins.

PMID- 9515971
TI  - A double-blind trial of fluoxetine in pathologic skin picking.
AB  - BACKGROUND: Our objective was to determine the efficacy of fluoxetine in the
      treatment of pathologic skin picking in a double-blind, placebo-controlled,
      parallel trial. METHOD: Twenty-one adults with chronic pathologic skin picking
      agreed to participate and received 10 weeks of placebo or fluoxetine with a
      flexible dosing schedule up to 80 mg/day. Three skin-picking measures were
      employed: the Clinical Global Impression-Improvement (CGI-I) scale, the Skin
      Picking Treatment Scale (SPTS), and a visual analog scale of self-rated change
      (VAS). In addition, depression, anxiety, and obsessions-compulsions were rated
      using the Hamilton Rating Scale for Depression (HAM-D), the Hamilton Rating Scale
      for Anxiety (HAM-A), the Spielberger State-Trait Anxiety Inventory (STAI), and
      the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) for the duration of the study.
      RESULTS: Seventeen subjects (6 treated with fluoxetine and 11 treated with
      placebo) completed the trial, at a mean fluoxetine dose of 55 mg/day. Fluoxetine
      was significantly superior to placebo in the treatment of skin picking according
      to two of the three measures for the completer analysis and to one of the three
      measures for the intent-to-treat analysis. Neither baseline level nor change in
      depression, anxiety, or obsessive-compulsive symptoms was significantly related
      to change in skin picking. CONCLUSION: This first controlled trial of the
      treatment of pathologic skin picking suggests that fluoxetine may be of
      therapeutic benefit. Larger controlled studies are warranted.

PMID- 9515973
TI  - Treatment of dementia with behavioral disturbance using divalproex or a
      combination of divalproex and a neuroleptic.
AB  - BACKGROUND: Neuroleptics have been used extensively to treat noncognitive
      behavioral disturbances in dementia, although their efficacy is only moderate and
      side effects are prominent. This study aims to determine the efficacy and
      tolerability of the non-neuroleptic divalproex sodium in patients with dementia
      and behavioral problems. METHOD: Charts of consecutive inpatients with dementia
      and behavioral problems according to DSM-IV were retrospectively reviewed.
      Patients treated with divalproex were analyzed for dosage, duration of divalproex
      treatment, levels, efficacy, side effects, and concurrent medications. Target
      behavioral symptoms were identified, and change was rated using a Clinical Global
      Impressions (CGI)-Severity of Illness scale. Patients who were much or very much
      improved were considered to be responders. RESULTS: Twenty-five patients (15 men
      and 10 women) with a mean+/-SD age of 77+/-7 years were identified. Fourteen
      (56%) of the 25 patients met our criteria for response after the addition of
      divalproex. Divalproex given alone was effective in 7 of 15 patients. Divalproex
      was added to an ongoing neuroleptic in 10 patients, and 7 patients responded.
      Patients received a mean final divalproex dose of 1650 mg/day with a mean blood
      level of 64 microg/mL. Divalproex was well tolerated in this population except
      for reversible sedation in 8 patients and transient worsening gait and confusion
      in 1 subject. CONCLUSION: Divalproex appeared to be as effective as previously
      reported rates for neuroleptics in the treatment of behavioral disturbances in
      dementia. The combination of divalproex and a neuroleptic was effective in
      patients who had failed either agent administered independently.

PMID- 9515972
TI  - Sleep changes after 4 consecutive days of venlafaxine administration in normal
      volunteers.
AB  - BACKGROUND: The purpose was to examine the effect of the antidepressant drug
      venlafaxine on sleep architecture and periodic leg movements of sleep (PLMS) in
      normal volunteers. METHOD: Eight normal volunteers were studied under laboratory
      sleep conditions as follows: 1 acclimatization night, 1 baseline night, and 4
      consecutive nights of venlafaxine p.o. administration (75 mg during the first 2
      nights and 150 mg the last 2 nights). RESULTS: Venlafaxine increased both wake
      time and sleep stage I. Sleep stages II and III were reduced. REM sleep time was
      reduced after the first venlafaxine dose, and, by the fourth night, REM sleep was
      completely suppressed in all volunteers. Six of the eight volunteers showed PLMS
      at a frequency above 25 per hour. CONCLUSION: Venlafaxine produces several sleep
      disturbances, which include abnormal leg movements.

PMID- 9515974
TI  - The effect of gender and age at onset of depression on mortality.
AB  - BACKGROUND: Depression has a marked negative impact on geriatric patient
      mortality and morbidity. The risk factors and exact reasons for these effects are
      not well understood. METHOD: Seeking to better define the factors, we
      retrospectively analyzed the effects of gender and age at onset of affective
      disorder in a naturalistic study of 192 geriatric patients consecutively admitted
      to a large midwestern tertiary care center between 1980 and 1987 for the
      treatment of unipolar depression. RESULTS: After controlling for age at index
      admission, patients with an onset of depression before age 40 suffered
      significantly (p < .05) less mortality in follow-up than those with onset after
      age 40. When effects of gender are examined, the effects of age at onset are most
      profound in women, with a threefold increase in the rate of death in the cohort
      with age at onset of depression after 70 years when compared to those with onset
      before age 40. CONCLUSION: These results and those of others suggest that
      depressed elderly women with no previous history of affective disorder are at a
      markedly increased risk compared with elderly women with a history of affective
      illness for morbidity and mortality and that a significant proportion of elderly
      depressed patients are admitted to a psychiatric hospital for a depression that
      is secondary to serious medical illness.

PMID- 9515975
TI  - Muscle dysmorphia.

PMID- 9515976
TI  - Antiepileptic drug augmentation for treatment-resistant depression.

PMID- 9515977
TI  - Cost-effectiveness of divalproex versus lithium.

PMID- 9515978
TI  - Clozapine use in two full-term pregnancies.

PMID- 9515979
TI  - Nefazodone and neurotoxicity.

PMID- 9515981
TI  - Implementing the FDA Modernization Act.

PMID- 9515980
TI  - Violent behavior during sleep.
AB  - BACKGROUND: Although the relative incidence of violent behavior during sleep
      (VBS) is presumed to be low, no epidemiologic data exist to evaluate the
      prevalence of the phenomenon or to begin to understand its precursors or
      subtypes. This study examined the frequency of violent or injurious behavior
      during sleep and associated psychiatric risk factors. METHOD: A representative
      United Kingdom sample of 2078 men and 2894 women between the ages of 15 to 100
      years (representing 79.6% of those contacted) participated in a telephone
      interview directed by the Sleep-EVAL expert system specially designed for
      conducting such diagnostic telephone surveys. RESULTS: Two percent (N = 106) of
      respondents reported currently experiencing VBS. The VBS group experienced more
      night terrors and daytime sleepiness than the non-VBS group. Sleep talking,
      bruxism, and hypnic jerks were more frequent within the VBS than the other group,
      as were hypnagogic hallucinations (especially the experience of being attacked),
      the incidence of smoking, and caffeine and bedtime alcohol intake. The VBS group
      also reported current features of anxiety and mood disorders significantly more
      frequently and reported being hospitalized more often during the previous 12
      months than the non-VBS group. Subjects with mood or anxiety disorders that co
      occurred with other nocturnal symptoms had a higher risk of reporting VBS than
      all other subjects. CONCLUSION: We have identified a number of sleep, mental
      disorder, and other general health factors that characterize those experiencing
      episodes of VBS. These findings suggest that specific factors, perhaps reflecting
      an interaction of lifestyle and hereditary contributions, may be responsible for
      the observed variability in this rare but potentially serious condition.

PMID- 9515983
TI  - From the Centers for Disease Control and Prevention. Public opinion about public
      health--California and the United States, 1996.

PMID- 9515982
TI  - Taking telemedicine to the top of the world.

PMID- 9515984
TI  - From the Centers for Disease Control and Prevention. State-specific prevalence of
      lapses in health-care-insurance coverage--United States, 1995.

PMID- 9515985
TI  - From the Centers for Disease Control and Prevention. Hyperthermia and dehydration
      related deaths associated with intentional rapid weight loss in three collegiate
      wrestlers--North Carolina, Wisconsin, and Michigan, November-December 1997.

PMID- 9515986
TI  - The public and the war on illicit drugs.
AB  - This article presents what Americans think about the policies subsumed under the
      label of the "War on Drugs." It is based on an analysis of 47 national surveys
      conducted between 1978 and 1997. The major results are that most Americans rely
      on the mass media for information about the scope of the drug abuse problem;
      Americans do not think that the Wars on Drugs have succeeded, but they do not
      want to quit on these efforts; weak support exists for increasing funding for
      drug treatment; support for preventive education has increased during the 1990s;
      criminal justice responses remain very popular; for many, illicit drug use is a
      moral rather than a public health issue; the public supports allowing physicians
      to prescribe marijuana for severe illness, but opposes the general legalization
      of marijuana and other illicit drugs; and needle exchange programs are supported
      by a bare majority, but only when they are told that the American Medical
      Association supports these programs.

PMID- 9515987
TI  - Controversies: the role of HIV specialists.

PMID- 9515988
TI  - Controversies: the role of HIV specialists.

PMID- 9515989
TI  - Controversies: the role of HIV specialists.

PMID- 9515990
TI  - Controversies: the role of HIV specialists.

PMID- 9515991
TI  - Controversies: the role of HIV specialists.

PMID- 9515992
TI  - Modern medicine and chaos theory.

PMID- 9515993
TI  - Modern medicine and chaos theory.

PMID- 9515994
TI  - Cost-effectiveness of the AHCPR guidelines for smoking.

PMID- 9515995
TI  - Cost-effectiveness of the AHCPR guidelines for smoking.

PMID- 9515996
TI  - Clinical crossroads: a young light-skinned woman with multiple moles.

PMID- 9515997
TI  - Clinical crossroads: a young light-skinned woman with multiple moles.

PMID- 9515998
TI  - Sodium reduction and weight loss in the treatment of hypertension in older
      persons: a randomized controlled trial of nonpharmacologic interventions in the
      elderly (TONE). TONE Collaborative Research Group.
AB  - CONTEXT: Nonpharmacologic interventions are frequently recommended for treatment
      of hypertension in the elderly, but there is a paucity of evidence from
      randomized controlled trials in support of this recommendation. OBJECTIVE: To
      determine whether weight loss or reduced sodium intake is effective in the
      treatment of older persons with hypertension. DESIGN: Randomized controlled
      trial. PARTICIPANTS: A total of 975 [corrected] men and women aged 60 to 80 years
      with systolic blood pressure lower than 145 mm Hg and diastolic blood pressure
      lower than 85 mm Hg while receiving treatment with a single antihypertensive
      medication. SETTING: Four academic health centers. INTERVENTION: The 585 obese
      participants were randomized to reduced sodium intake, weight loss, both, or
      usual care, and the 390 nonobese participants were randomized to reduced sodium
      intake or usual care. Withdrawal of antihypertensive medication was attempted
      after 3 months of intervention. MAIN OUTCOME MEASURE: Diagnosis of high blood
      pressure at 1 or more follow-up visits, or treatment with antihypertensive
      medication, or a cardiovascular event during follow-up (range, 15-36 months;
      median, 29 months). RESULTS: The combined outcome measure was less frequent among
      those assigned vs not assigned to reduced sodium intake (relative hazard ratio,
      0.69; 95% confidence interval [CI], 0.59-0.81; P<.001) and, in obese
      participants, among those assigned vs not assigned to weight loss (relative
      hazard ratio, 0.70; 95% CI, 0.57-0.87; P<.001). Relative to usual care, hazard
      ratios among the obese participants were 0.60 (95% CI, 0.45-0.80; P<.001) for
      reduced sodium intake alone, 0.64 (95% CI, 0.49-0.85; P=.002) for weight loss
      alone, and 0.47 (95% CI, 0.35-0.64; P<.001) for reduced sodium intake and weight
      loss combined. The frequency of cardiovascular events during follow-up was
      similar in each of the 6 treatment groups. CONCLUSION: Reduced sodium intake and
      weight loss constitute a feasible, effective, and safe nonpharmacologic therapy
      of hypertension in older persons.

PMID- 9515999
TI  - Early inpatient rehabilitation after elective hip and knee arthroplasty.
AB  - CONTEXT: Inpatient rehabilitation after elective hip and knee arthroplasty is
      often necessary for patients who cannot function at home soon after surgery, but
      how soon after surgery inpatient rehabilitation can be initiated has not been
      studied. OBJECTIVE: To test the hypothesis that high-risk patients undergoing
      elective hip and knee arthroplasty would incur less total cost and experience
      more rapid functional improvement if inpatient rehabilitation began on
      postoperative day 3 rather than day 7, without adverse consequences to the
      patients. DESIGN: Randomized controlled trial conducted from 1994 to 1996.
      SETTING: Tertiary care center. PARTICIPANTS: A total of 86 patients undergoing
      elective hip or knee arthroplasty and who met the following criteria for being
      high risk: 70 years of age or older and living alone, 70 years of age or older
      with 2 or more comorbid conditions, or any age with 3 or more comorbid
      conditions. Of the 86 patients, 71 completed the study. INTERVENTIONS: Random
      assignment to begin inpatient rehabilitation on postoperative day 3 vs
      postoperative day 7. MAIN OUTCOME MEASURES: Total length of stay and cost from
      orthopedic and rehabilitation hospital admissions, functional performance in
      hospitals using a subset of the functional independence measure, and 4-month
      follow-up assessment using the RAND 36-item health survey I and the functional
      status index. RESULTS: Patients who completed the study and began inpatient
      rehabilitation on postoperative day 3 exhibited shorter mean (+/-SD) total length
      of stay (11.7+/-2.3 days vs 14.5+/-1.9, P<.001), lower mean (+/-SD) total cost
      ($25891+/-$3648 vs $27762+/-$3626, P<.03), more rapid attainment of short-term
      functional milestones between days 6 and 10 (36.2+/-14.4 m ambulated vs 21.4+/
      13.3 m, P<.001; 4.8+/-0.8 mean transfer functional independence measure score vs
      4.3+/-0.7, P<.01), and equivalent functional outcome at 4-month follow-up.
      CONCLUSION: These data showed that high-risk individuals were able to tolerate
      early intensive rehabilitation, and this intervention yielded faster attainment
      of short-term functional milestones in fewer days using less total cost.

PMID- 9516000
TI  - Primary care physician compensation method in medical groups: does it influence
      the use and cost of health services for enrollees in managed care organizations?
AB  - CONTEXT: Growth of at-risk managed care contracts between health plans and
      medical groups has been well documented, but less is known about the nature of
      financial incentives within those medical groups or their effects on health care
      utilization. OBJECTIVE: To test whether utilization and cost of health services
      per enrollee were influenced independently by the compensation method of the
      enrollee's primary care physician. DESIGN: Survey of medical groups contracting
      with selected managed care health plans, linked to 1994 plan enrollment and
      utilization data for adult enrollees. SETTING: Medical groups, major managed care
      health plans, and their patients/enrollees in the state of Washington. STUDY
      PARTICIPANTS: Sixty medical groups in Washington, 865 primary care physicians
      (internal medicine, pediatrics, family practice, or general practice) from those
      groups and affiliated with 1 or more of 4 managed care health plans, and 200 931
      adult plan enrollees. INTERVENTION: The effect of method of primary care
      physician's compensation on the utilization and cost of health services was
      analyzed by weighted least squares and random effects regression. MAIN OUTCOME
      MEASURES: Total visits, hospital days, and per member per year estimated costs.
      RESULTS: Compensation method was not significantly (P>.30) related to utilization
      and cost in any multivariate analyses. Patient age (P<.001), female gender
      (P<.001), and plan benefit level (P<.001) were significantly positively related
      to visits, hospital days, and per member per year costs. The primary care
      physician's age was significantly negatively related (P<.001) to all 3 dependent
      measures. CONCLUSIONS: Compensation method was not significantly related to use
      and cost of health services per person. Enrollee, physician, and health plan
      benefit factors were the prime determinants of utilization and cost of health
      services.

PMID- 9516001
TI  - Wound botulism associated with black tar heroin among injecting drug users.
AB  - CONTEXT: Wound botulism (WB) is a potentially lethal, descending, flaccid,
      paralysis that results when spores of Clostridium botulinum germinate in a wound
      and elaborate neurotoxin. Since 1988, California has experienced a dramatic
      increase in WB associated with injecting "black tar" heroin (BTH), a dark, tarry
      form of the drug. OBJECTIVE: To identify risk factors for WB among injecting drug
      users (IDUs). DESIGN: Case-control study based on data from in-person and
      telephone interviews. PARTICIPANTS: Case patients (n=26) were IDUs who developed
      WB from January 1994 through February 1996. Controls (n=110) were IDUs newly
      enrolled in methadone detoxification programs in 4 counties. MAIN OUTCOME
      MEASURES: Factors associated with the development of WB. RESULTS: Among the 26
      patients, the median age was 41.5 years, 15 (58%) were women, 14 (54%) were non
      Hispanic white, 11 (42%) were Hispanic, and none were positive for the human
      immunodeficiency virus. Nearly all participants (96% of patients and 97% of
      controls) injected BTH, and the mean cumulative dose of BTH used per month was
      similar for patients and controls (27 g and 31 g, respectively; P=.6). Patients
      were more likely than controls to inject drugs subcutaneously or intramuscularly
      (92% vs 44%, P<.001) and used this route of drug administration more times per
      month (mean, 67 vs 24, P<.001), with a greater cumulative monthly dose of BTH
      (22.3 g vs 6.3 g, P<.001). A dose-response relationship was observed between the
      monthly cumulative dose of BTH injected subcutaneously or intramuscularly and the
      development of WB (chi2 for linear trend, 26.5; P<.001). In the final regression
      model, subcutaneous or intramuscular injection of BTH was the only behavior
      associated with WB among IDUs (odds ratio, 13.7; 95% confidence interval, 3.0
      63.0). The risk for development of WB was not affected by cleaning the skin,
      cleaning injection paraphernalia, or sharing needles. CONCLUSIONS: Injection of
      BTH intramuscularly or subcutaneously is the primary risk factor for the
      development of WB. Physicians in the western United States, where BTH is widely
      used, should be aware of the potential for WB to occur among IDUs.

PMID- 9516002
TI  - Tennessee's failed managed care program for mental health and substance abuse
      services.
AB  - In July 1996, Tennessee initiated a managed mental health and substance abuse
      program called TennCare Partners. This publicly funded "carve-out" experiment
      started chaotically and soon deteriorated into a crisis. Many patients did not
      receive care or lost continuity of care, and the traditional "safety net" mental
      health system nearly disintegrated. This qualitative case study sought to
      ascertain the impact of the TennCare Partners program. It points out that the
      program's difficulties stemmed directly from a flawed design that spread funds
      previously earmarked for severely mentally ill patients across the entire
      Medicaid population. States contemplating similar reforms should strive to
      protect vulnerable patients by risk-adjusting capitation payments and by focusing
      resources on care for severely mentally ill persons. States should also minimize
      program complexity and ensure the accountability of managed care networks for
      their patients' behavioral health care needs.

PMID- 9516003
TI  - Medical examiner and coroner systems: history and trends.
AB  - CONTEXT: Medical legal investigations in the United States (primarily unnatural
      or suspected unnatural deaths) are carried out by medical examiner or coroner
      systems. Medical examiners-usually physicians and generally with training in
      pathology, medicolegal death investigation, and performance of forensic autopsies
      generally have greater expertise in unnatural death investigations than do
      coroners. OBJECTIVE: To document the locations and implementation year for states
      and counties that have medical examiner systems that have replaced coroner
      systems or that are defined in statute and assist coroners in their
      investigations. DESIGN: Review of published information and national survey in
      1997. SETTING: United States. PARTICIPANTS: County medical examiners and state
      medical examiners or their administrators. MAIN OUTCOME MEASURES: The location of
      states and counties with medical examiner systems, the implementation year for
      each system, and the proportion of counties and population served by medical
      examiner systems. RESULTS: A total of 79 of 91 county medical examiners
      responded. A total of 36 states have at least 1 medical examiner system at the
      county, district, or state level in which there is no coroner involved in the
      death investigation process. Only 22 states have medical examiner death
      investigation systems in place and have no coroners in the state. Among 13 states
      in which some counties have coroner systems and some have medical examiner
      systems, medical examiner systems exist in 8% of counties and serve 43% of the
      population. Medical examiner systems that operate without coroner involvement
      serve about 48% of the population nationwide. Few state or county medical
      examiner systems have been implemented since 1990. CONCLUSIONS: In this century,
      medical examiner systems have gradually replaced coroner systems, but such change
      has slowed in recent years, with medical examiner systems now serving about 48%
      of the national population.

PMID- 9516004
TI  - Antibiotic prescribing for children with colds, upper respiratory tract
      infections, and bronchitis.
AB  - CONTEXT: The spread of antibiotic-resistant bacteria is associated with
      antibiotic use. Children receive a significant proportion of the antibiotics
      prescribed each year and represent an important target group for efforts aimed at
      reducing unnecessary antibiotic use. OBJECTIVE: To evaluate antibiotic
      prescribing practices for children younger than 18 years who had received a
      diagnosis of cold, upper respiratory tract infection (URI), or bronchitis in the
      United States. DESIGN: Representative national survey of practicing physicians
      participating in the National Ambulatory Medical Care Survey conducted in 1992
      with a response rate of 73%. SETTING: Office-based physician practices.
      PARTICIPANTS: Physicians completing patient record forms for patients younger
      than 18 years. MAIN OUTCOME MEASURES: Principal diagnoses and antibiotic
      prescriptions. RESULTS: A total of 531 pediatric office visits were recorded that
      included a principal diagnosis of cold, URI, or bronchitis. Antibiotics were
      prescribed to 44% of patients with common colds, 46% with URIs, and 75% with
      bronchitis. Extrapolating to the United States, 6.5 million prescriptions (12% of
      all prescriptions for children) were written for children diagnosed as having a
      URI or nasopharyngitis (common cold), and 4.7 million (9% of all prescriptions
      for children) were written for children diagnosed as having bronchitis. After
      controlling for confounding factors, antibiotics were prescribed more often for
      children aged 5 to 11 years than for younger children (odds ratio [OR], 1.94; 95%
      confidence interval [CI], 1.13-3.33) and rates were lower for pediatricians than
      for nonpediatricians (OR, 0.57; 95% CI, 0.35-0.92). Children aged 0 to 4 years
      received 53% of all antibiotic prescriptions, and otitis media was the most
      frequent diagnosis for which antibiotics were prescribed (30% of all
      prescriptions). CONCLUSIONS: Antibiotic prescribing for children diagnosed as
      having colds, URIs, and bronchitis, conditions that typically do not benefit from
      antibiotics, represents a substantial proportion of total antibiotic
      prescriptions to children in the United States each year.

PMID- 9516005
TI  - Setting the TONE for ending the hypertension epidemic.

PMID- 9516007
TI  - Why do physicians prescribe antibiotics for children with upper respiratory tract
      infections?

PMID- 9516006
TI  - Inpatient rehabilitation after total joint replacement.

PMID- 9516008
TI  - Airway inflammation and severe asthma: abstract and commentary.

PMID- 9516009
TI  - Fetal renal biopsies in obstructive uropathy: feasibility and clinical
      correlations--preliminary results.
AB  - Final assessment on the outcome of fetal obstructive uropathy is a challenging
      matter. Ultrasonography, fetal urine electrolytes, and beta 2 microglobulin are
      postulated as being useful in many cases. For cases in which renal function
      remains unclear, ultrasound-guided fetal kidney biopsy may be used in order to
      detect histologic features distinctive of renal dysplasia. We present preliminary
      results aimed at studying the feasibility and possible risks. Biopsies were
      initially performed in 11 severely malformed fetuses, three of them with
      associated renal abnormalities. The success rate in obtaining renal material was
      63.6 per cent with no maternal complications. In the next phase of this study,
      ten biopsies and urine collections were performed in fetuses with bilateral
      obstructive uropathy. The success rate was 50 per cent with no complications.
      Normal fetal renal histology was seen in 80 per cent of cases. In one case,
      although electrolytes were normal, a histologic diagnosis of renal dysplasia was
      made, showing a good correlation with outcome. In conclusion, fetal kidney
      biopsies for obstructive uropathy are feasible and further studies are needed to
      show their clinical relevance and risks.

PMID- 9516010
TI  - Exclusion of uniparental inheritance of chromosome 15 in a fetus with a familial
      dicentric (Y;15) translocation.
AB  - We present a prenatal case with a 45,X,dic(Y;15) (q11.23;p11.1) karyotype and
      describe the inheritance pattern of the chromosome 15s. Chromosome 15 has an
      imprinted region and inheritance of both chromosome 15 from one parent results in
      either Angelman syndrome (AS) (paternal inheritance) or Prader Willi syndrome
      (PWS) (maternal inheritance). Parental chromosome studies revealed that the
      father carried the same dicentric (Y;15) translocation. Since familial chromosome
      rearrangements can result in aberrant chromosomal segregation during meiosis, we
      wanted to exclude paternal uniparental inheritance of chromosome 15. By using DNA
      microsatellite markers at several 15q11q13 loci, we determined that the fetus had
      inherited his normal non-translocated chromosome 15 from his mother.

PMID- 9516011
TI  - Prenatal diagnosis of heterozygosity for biotinidase deficiency by enzymatic and
      molecular analyses.
AB  - Biotinidase deficiency is characterized by neurological and cutaneous
      abnormalities that can be prevented or ameliorated by oral biotin therapy. A
      child with biotinidase deficiency went undiagnosed for a long period and has
      irreversible neurological deficits despite biotin treatment. This child is
      homozygous for the most common mutation (G98:d7i3) found in symptomatic children
      with the disorder. The parents insisted on having prenatal diagnosis in a
      subsequent pregnancy to alleviate their anxiety about having another affected
      child. Mutation analysis of DNA obtained directly from amniotic fluid and from
      cultured amniocytes revealed that the fetus was heterozygous for the mutation.
      Maternal cell contamination of the amniocytes was excluded by genotype analysis.
      Biotinidase activity in extracts of cultured amniocytes revealed 40 per cent of
      mean normal activity. At birth, the infant was confirmed to be heterozygous by
      serum enzyme analysis. This is the first report of the use of molecular analysis
      for the prenatal diagnosis for biotinidase deficiency.

PMID- 9516012
TI  - Is maternal serum triple screening a better predictor of Down syndrome in female
      than in male fetuses?
AB  - Among euploid gestations, female fetuses have been reported to have significantly
      lower maternal serum alpha-fetoprotein (MSAFP) and higher human chorionic
      gonadotropin (hCG) levels than male fetuses. Since in maternal serum triple
      screening, low MSAFP and high hCG MOM independently confer greater risk of a Down
      syndrome fetus, we investigated the hypothesis that maternal serum triple
      screening is more efficacious at detecting female than male Down syndrome
      fetuses. A database containing all karyotypes from amniocentesis performed
      between August 1994 and August 1996 was accessed. All trisomy 21 cases were
      identified. The male-to-female ratio among trisomy 21 fetuses detected at
      amniocentesis after abnormal maternal serum triple screening was compared with
      that among trisomy 21 fetuses detected at amniocentesis for advanced maternal age
      (AMA), which served as the control group. Statistical analysis utilized chi
      square, Fisher's exact test, and Student's t-test. A P value of less than 0.05
      was considered statistically significant. Forty-nine trisomy 21 fetuses were
      detected in the women who underwent amniocentesis because of abnormal triple
      screening and 311 were detected in the control group. The proportion of male
      fetuses among the triple screening group was not significantly different from
      that of the AMA group (55 per cent vs. 57 per cent; P=0.9). Our study had a power
      of 80 per cent to detect a difference of 25 per cent in the male-to-female ratio
      (alpha=0.05, beta=0.20). The reported differences in MSAFP and hCG levels between
      male and female euploid fetuses do not appear to affect the sex ratio among Down
      syndrome fetuses detected because of an abnormal maternal serum triple screening.

PMID- 9516013
TI  - Ultrasonographic dimensions of the vertical span of the fetal iliac bone and
      relationship with some fetal parameters.
AB  - Using fetal ultrasonography, disorders of developmental delay and congenital
      malformations are promptly diagnosed. Skeletal abnormalities are relatively easy
      to notice once standards of growth are established. The iliac bone is frequently
      affected in skeletal problems, yet it has not been extensively studied. In this
      study, a total of 296 fetuses were evaluated and the vertical span of the iliac
      bone was measured in the oblique coronal plane. The size of the fetal iliac bone
      (in cm) was calculated according to the cubic regression formula y = -4.6891 +
      0.5757x (gestational age in weeks) - 0.0159x2 + 0.0001x3. Standards of normal
      vertical growth of the iliac bone were established and it was noted that the
      humerus/iliac bone and femur/iliac bone ratios were uniform with minimal
      variation after the 16th gestational week, with mean values (SD) of 1.82 (0.14)
      and 2.09 (0.15), respectively. The iliac wing may be unaltered and the vertical
      span may be changed considerably in some skeletal dysplasias. For complete
      evaluation of the skeletal system and to distinguish between different conditions
      with different prognoses and outcomes, measurement of the vertical span of the
      iliac bone as a complementary measurement is recommended.

PMID- 9516014
TI  - Evaluation of first-trimester screening by fetal nuchal translucency and maternal
      age.
AB  - The aim of this screening study was to evaluate first-trimester screening for
      chromosomal defects by fetal nuchal translucency thickness at 10-14 weeks of
      gestation in four Fetal Medicine Units in Greece. Estimates of the risk for
      trisomy 21 were calculated taking into account fetal nuchal translucency
      thickness and maternal age. There were 3550 cases; the median maternal age was 29
      years (range 16-48 years); and 277 (7.8 per cent) were over 37 years. The median
      crown rump length was 60 mm (range 38-85 mm) and the fetal nuchal translucency
      thickness increased with crown rump length and measurements were above the 95th
      centile in 101 (2.9 per cent) of the cases. The adjusted risk was 1 in 300 or
      more in 172 (4.9 per cent) of the cases and the high-risk group contained ten of
      the 11 (91 per cent) fetuses with trisomy 21 and all 11 fetuses with other
      chromosomal defects. The findings of this study provide further evidence for the
      high efficacy of screening for chromosomal abnormalities by fetal nuchal
      translucency and maternal age.

PMID- 9516015
TI  - Circulatory changes following intrauterine closure of the ductus arteriosus in
      the human fetus and newborn.
AB  - Prenatal detection of intrauterine closure of the ductus arteriosus unrelated to
      maternal administration of non-steroidal anti-inflammatory drugs or
      glucocorticoids made it possible to study the circulation in this condition in
      the human fetus and newborn by pre- and postnatal echocardiography and neonatal
      cardiac catheterization. At 38 weeks, the fetus presented intrauterine ductal
      closure associated with right ventricular dilatation and marked hypertrophy of
      the right ventricle and the interventricular septum, as well as severely
      diminished right ventricular fractional shortening and diminished pulmonary blood
      flow. Blood flow redistribution was characterized by reduced blood flow through
      the right heart and increased right-to-left shunting across the dilated foramen
      ovale. Pathological Doppler waveforms of the inferior vena cava and the ductus
      venosus were found, although the cardiotocogram was normal. Following
      unsuccessful induction of labour a Caesarean section was performed. Postnatal
      echocardiography confirmed the prenatal findings. Cardiac catheterization,
      performed because of persistent dependence on additional oxygen administration,
      revealed increased pulmonary vascular resistance, reduced pulmonary blood flow,
      and prolonged right-to-left shunt across the foramen ovale. Reduced peripheral
      pulmonary artery diameters were shown angiographically. Follow-up examinations
      revealed regression of right ventricular hypertrophy and recovery of right
      ventricular and pulmonary function. The findings confirm results from
      haemodynamic studies in animal experiments.

PMID- 9516016
TI  - Maternal serum levels of free beta-hCG and PAPP-A in the first trimester of
      pregnancy are not associated with subsequent fetal growth retardation or preterm
      delivery.
AB  - The purpose of this case-control study was to examine the association of first
      trimester concentrations of free beta-human chorionic gonadotropin (free beta
      hCG) and pregnancy-associated plasma protein A (PAPP-A) in maternal serum with
      subsequent preterm delivery or small-for-gestational age (SGA) fetuses. We
      collected all the blood samples before chorionic villus sampling in the first
      trimester. Concentrations of free beta-hCG and PAPP-A were expressed in multiples
      of the median (MOM) for gestational age. We compared the levels of both analytes
      in 73 SGA pregnancies (birth weight below the fifth percentile) with those in 292
      normal controls, who were matched for gestational age, maternal age, parity,
      maternal weight, and smoking habits. We also compared the levels in 87
      pregnancies with a preterm delivery (delivery before 37 completed weeks) with
      those in 348 matched controls. The median concentrations of PAPP-A and free beta
      hCG, expressed in MOMs, in the 73 SGA pregnancies were 0.83 and 0.95,
      respectively, compared with 0.98 and 1.01, respectively, in the 292 matched
      controls (P=0.08 and 0.19, respectively). In the 87 pregnancies with a preterm
      delivery, the median concentrations of PAPP-A and free beta-hCG were 0.98 and
      0.94, respectively, compared with 0.99 and 0.99, respectively, in the 348 matched
      controls (P=0.82 and 0.10, respectively). In contrast with the maternal serum
      analytes used in second-trimester screening--alpha-fetoprotein and human
      chorionic gonadotropin--this study showed that concentrations of PAPP-A and free
      beta-hCG in the first trimester were not associated with subsequent fetal growth
      retardation or preterm delivery.

PMID- 9516018
TI  - Prenatal diagnosis of Charcot-Marie-Tooth disease.

PMID- 9516017
TI  - On what grounds do women participate in prenatal screening?
AB  - Along with the rapid biomedical development of prenatal screening tests, target
      groups' attitudes and decision-making about, and the acceptance of, screening
      procedures have come into focus. To understand users' decision-making, it is
      essential to understand users' knowledge and perceptions of a procedure. The aim
      of this study was to examine Finnish women's knowledge and perceptions of, and
      stated reasons to participate in, two prenatal screening tests: serum screening
      and mid-trimester ultrasound screening. Subjects (n=1035) for the serum screening
      survey were catered for in the maternity care centres of two Finnish towns, where
      serum screening is available for all pregnant women. After one reminder, 88 per
      cent returned the questionnaire. Subjects (n=497) for the mid-trimester
      ultrasound screening survey were catered for in the obstetrical and
      gynaecological outpatient clinic of the city hospital of another town; the
      response rate was 85 per cent. Women's perceptions of the studied prenatal
      screening tests, serum screening and mid-trimester ultrasound screening, differed
      significantly, even though both are used to detect fetal malformations. Serum
      screening was far more often perceived to be connected with finding diseases or
      abnormalities than ultrasound screening. Another interesting finding was that the
      stated reasons for screening in general and the subjective reasons for
      participation were different. Reassurance was the personal reason most often
      mentioned in both the serum screening and the ultrasound group. Almost all women
      had the most superficial knowledge about serum screening; they knew whether it
      had been offered and that it is done to screen for Down syndrome. The greatest
      gaps in knowledge concerned the sensitivity of serum screening, its use in
      screening for congenital nephrosis, and diagnostic tests and their risks.
      Knowledge was poorer among women without a high school education. When
      counselling women about prenatal screening tests, more emphasis should be given
      to the sensitivity of serum screening, all of its screening uses, and the
      possible diagnostic tests and their risks. The fact that ultrasound screening can
      detect conditions which may lead to the possibility of a selective abortion
      should also be explained more fully.

PMID- 9516019
TI  - Case report: cerebellar hemi-hypoplasia.
AB  - Cerebellar hypoplasia is a prominent feature of fetal brain pathology. The lesion
      is rarely isolated or asymmetric. Various aetiological factors have been
      proposed. The frequency of cerebellar hypoplasia as a congenital defect in humans
      is unknown. A single case is described of unilateral cerebellar hypoplasia with
      intact vermis that was detected on prenatal ultrasound examination. Changes in
      the appearance of the abnormality over the course of the pregnancy raised the
      possibility of a disruptive vascular aetiology with destruction of normally
      formed structures. Prenatal ultrasound, post-delivery cranial ultrasound, and MRI
      images are presented to support the hypothesis.

PMID- 9516020
TI  - Familial supernumerary marker chromosome evolution through three generations.
AB  - A mosaic chromosome complement, 46,XY/47,XY,+r(15), was detected at prenatal
      diagnosis. Family studies showed the mother and one of her two children to have a
      bisatellited supernumerary marker chromosome (SMC) in all lymphocytes examined.
      The maternal grandfather also showed a bisatellited SMC, but in only 2 per cent
      of his lymphocytes. NOR, DA/DAPI, and chromosome 15 centromere and short arm
      specific probes confirmed the identify of the bisatellited SMC and of ring SMC as
      derived from chromosome 15. An apparently normal male was born at full term. At
      age 1 year, the baby continues to have normal growth and development. The
      bisatellited 15 likely originated by somatic mutation in the grandfather (2 per
      cent cells), was transmitted unchanged to the daughter and grandson (germline
      transmission, no mosaicism), and then evolved by excising the satellites and
      forming a ring SMC in the index case. Progressive changes in the frequency and
      subsequent changes in the structure of this SMC illustrate the unusual
      characteristics of chromosome 15.

PMID- 9516021
TI  - Intrauterine adenoviral infection associated with fetal non-immune hydrops.
AB  - A 27-week fetus with hydrops fetalis associated with fetal tachyarrhythmia and
      adenovirus infection was documented by viral polymerase chain reaction (PCR). The
      fetal tachyarrhythmia was converted to normal sinus rhythm by maternal
      pharmacological therapy with digoxin. Subsequently, resolution of the hydropic
      changes occurred and a viable normal-appearing preterm fetus at 29 weeks'
      gestation was delivered after preterm labour. This case demonstrates the first
      documented report of intrauterine adenovirus-associated fetal tachyarrhythmia and
      hydrops fetalis.

PMID- 9516022
TI  - Genetic amniocentesis following multifetal pregnancy reduction does not increase
      the risk of pregnancy loss.
AB  - A collaborative, retrospective study of patients who had undergone multifetal
      pregnancy reduction (MFPR) to twins and subsequent genetic amniocentesis was
      performed to determine if amniocentesis increased the risk of pregnancy loss.
      Seventy-nine patients from three centres underwent MFPR and subsequent
      amniocentesis. The pregnancy loss rate was 5.06 per cent in this group. In
      comparison, the loss rate from a control collaborative series of patients who
      underwent MFPR only was 11.19 per cent, which was not statistically different.
      Thus, it appears that amniocentesis following MFPR is unlikely to increase the
      pregnancy loss rate.

PMID- 9516023
TI  - Rapid assessment of amniotic fluid by primed in situ labelling (PRINS) for
      suspected fetal trisomy 18.

PMID- 9516024
TI  - Current awareness in prenatal diagnosis.

PMID- 9516025
TI  - Issues of method-specificity and -dependency of blood pressure data: lack of
      reporting of methodological specifications.

PMID- 9516026
TI  - European network for the case-population surveillance of rare diseases (Euronet).
      A prospective feasibility study.
AB  - OBJECTIVE: Euronet, a case-population surveillance scheme, aims to estimate the
      risk of certain rare conditions which are commonly iatrogenic, by comparing drug
      use amongst non-selective cases with overall drug use in the general population.
      METHODS: The method is based on three provisos: (1) all incident cases
      (irrespective of suspected aetiology) should be ascertained and studied; (2) a
      full drug history should be obtained from cases by direct interview; and (3) drug
      use data for the products of interest should be available for this population
      from which cases are chosen. The feasibility of this problem-oriented approach
      for the identification of new signals of adverse drug reactions and for risk
      estimation will be tested in relation to agranulocytosis, Stevens-Johnson
      syndrome and toxic epidermal necrolysis in four defined areas in Europe,
      totalling 19 x 10(6) inhabitants, with these latest two outcomes being studied in
      only three regions. The design, methods and main limitations of this case
      population surveillance approach are described.

PMID- 9516027
TI  - Analgesic efficacy of ibuprofen alone and in combination with codeine or caffeine
      in post-surgical pain: a meta-analysis.
AB  - OBJECTIVE: To estimate the analgesic effect of ibuprofen and to test whether
      codeine and caffeine enhance its effect on post-surgical pain. METHOD: Systematic
      overview of the literature and meta-analysis of published randomised, controlled
      trials. RESULTS: Ibuprofen is effective in dental pain, episiotomy pain and other
      post-operative pain. There is a dose response relationship over the range 50-400
      mg. The difference in total pain-relief score relative to placebo was 19-31%. On
      average, patients were over three times more likely to obtain moderate to
      excellent pain relief with ibuprofen than with placebo (response-rate ratio =
      3.45) and the number needed to treat was 2.44. Codeine 60 mg enhanced the
      analgesic effect of ibuprofen 400 mg by about 8% in the total pain-relief scale,
      but it also increased its adverse effects. The additive effect of caffeine was
      inconsistent. CONCLUSION: Ibuprofen is an effective analgesic in post-operative
      pain. Codeine 60 mg adds to the analgesic effect of ibuprofen 400 mg. Any
      additive caffeine effect requires validation.

PMID- 9516028
TI  - Rubber emboli.
AB  - OBJECTIVE: To investigate the potential for embolisation, due to the piercing of
      suspect rubber seals ('coring') of intravenous (IV)-solution bottles by the sharp
      (plastic, non-patient end) spike of commonly used infusion sets. METHODS: The
      suspect seals of 50 bottles were pierced with an infusion-set spike and the
      respective solutions were examined for visible particles, filtered and the
      filtrate examined both macroscopically and microscopically. As controls, 36 IV
      solution bottles of other brands with pierced seals and 10 units of the suspect
      brand with unpierced seals were examined in the same way. RESULTS: Macroscopic
      and microscopic particles (maximum longest axis > 1 mm), including fibrils, were
      invariably present in the solutions from bottles with pierced suspect seals, but
      no such debris was detected in the control solutions. CONCLUSIONS: The
      defectively packaged solutions (from B. Braun) have been used extensively in at
      least 21 different countries during the past decade and, unknown to clinicians,
      constituted a source of potential rubber emboli. The multinational manufacturer
      responsible has largely rectified the fault. Discovery of such defects requires
      prompt reporting to relevant government departments and the manufacturer, so that
      appropriate action may be taken nationally and internationally. Good
      manufacturing practice and drug regulatory surveillance should extend to the way
      in which the final packaged forms are used.

PMID- 9516029
TI  - Adrenocortical activity with repeated administration of one-daily inhaled
      fluticasone propionate and budesonide in asthmatic adults.
AB  - OBJECTIVE: The aim of this study was to evaluate the steady-state effects of once
      daily inhaled fluticasone propionate (FP) and budesonide (BUD) on adrenocortical
      activity in asthmatic patients. METHODS: Ten asthmatic patients with a mean age
      of 31.2 years, a mean forced expiratory volume in 1 s (FEV1) of 91% predicted and
      a forced mid-expiratory flow (FEF25-75) of 62.3% predicted were studied in a
      single-blind randomised crossover design comparing placebo (PL), FP (375 microg
      per day and 750 microg per day) and BUD (400 microg per day and 800 microg per
      day) all given once daily for 4 days at each dose via a pressurised metered dose
      inhaler (pMDI) at 0800 hours. After 4 days of treatment, plasma cortisol was
      measured at 0800 hours (24 h after the last dose) and a 10-h overnight urine
      collection was taken, 14 h after the last dose (2200-0800 hours) for analysis of
      cortisol and creatinine excretion. RESULTS: Plasma cortisol levels (nmol.l(-1),
      as geometric mean) at 0800 hours demonstrated a significant difference between
      the highest doses of FP and BUD (424.1 vs 510.3 nmol.l(-1), respectively) but not
      between the low doses (506.8 vs 514.9 nmol.l(-1); PL 532.2 nmol.l(-1)). For the
      highest dose FP (750 microg) this equated to 20% suppression of 0800 hours plasma
      cortisol. Likewise, for overnight urinary cortisol output (nmol.10 h(-1) as
      geometric mean), there was a significant difference at the high doses of FP and
      BUD (25.5 vs 38.2 nmol.10 h(-1)), but not at the low doses 31.3 vs 34.8 nmol.10
      h(-1); PL 32.0 nmol.10 h(-1). For the overnight urinary cortisol/creatinine ratio
      (nmol.mmol(-1), as geometric mean) there was a similar trend; 4.5 vs 6.1
      nmol.mmol(-1) for high dose and 5.6 vs 6.3 nmol.mmol(-1) for low dose; PL 5.9
      nmol.mmol(-1). CONCLUSION: Repeated doses of FP 750 microg once daily caused
      greater adrenal suppression than BUD 800 microg once daily, when comparing
      effects on plasma cortisol levels at 0800 hours, 24 h after the last dose, as
      well as effects on overnight urinary cortisol output. Neither FP 375 microg once
      daily nor BUD 400 microg once daily produced detectable adrenal suppression.

PMID- 9516030
TI  - Lack of acetaminophen ceiling effect on R-III nociceptive flexion reflex.
AB  - OBJECTIVE: The analgesic efficacy of intravenous doses of acetaminophen
      (paracetamol) 0.5 g, 1 g and 2 g (administered as propacetamol) was assessed in
      11 healthy subjects in a randomised, double-blind, placebo-controlled crossover
      study. The antinociceptive effect was assessed over 8 h by measurement of the
      nociceptive flexion reflex threshold (R-III) in response to selective
      transcutaneous electrical stimulations. RESULTS: After acetaminophen 0.5 g, R-III
      increased to a mean maximum of 23% over baseline values; after 1 g to 28%, and
      after 2 g to 40%. The AUC(0-8 h) of the analgesic effects and the AUC(0-8 h) of
      plasma concentrations closely correlated and were dose-dependent: rs = 0.37, for
      R-III and rs = 0.94, for the plasma concentrations. Intravenous acetaminophen
      exerted a dose-dependent central antinociceptive effect.

PMID- 9516031
TI  - Variability of morphine disposition during long-term subcutaneous infusion in
      terminally ill cancer patients.
AB  - OBJECTIVE: To study the plasma concentrations of morphine and its glucuronides to
      assess the intra- and interindividual variability of the disposition of morphine
      administered by subcutaneous infusion in cancer patients. METHODS: Blood samples
      were taken repeatedly in eight patients with severe cancer pain who were being
      treated with morphine (60-3000 mg per day) via chronic (8-160 days) subcutaneous
      infusion. Venous blood samples were collected at least weekly and, when possible,
      on 3 consecutive days after dose adaptation or any other major change in the
      patients' treatment. Concentrations of morphine and its glucuronides in plasma
      were measured after solid-phase extraction using a validated high-performance
      liquid chromatography assay. The stability of the morphine solutions was
      determined by repeated measurement of the concentrations of morphine and its
      degradation products in the solutions. RESULTS: The morphine concentration in the
      infusion solutions remained unchanged during storage and infusion. The plasma
      concentrations of morphine and its glucuronides were within the ranges reported
      in the literature. There was, as expected, a large interindividual variability:
      from patient to patient, the mean of the normalised plasma concentrations ranged
      from 0.3 ng.ml(-1).mg(-1) to 0.8 ng.ml(-1).mg(-1) for morphine, from 1.0 ng.ml(
      1).mg(-1) to 3.1 ng.ml(-1).mg(-1) for morphine-6-glucuronide and from 6.8 ng.ml(
      1).mg(-1) to 24.3 ng.ml(-1).mg(-1) for morphine-3-glucuronide. Intraindividual
      variability was also important. The residual standard deviation of the mean
      normalised plasma concentrations calculated for each patient ranged from 26% to
      56% for morphine, from 20% to 51% for morphine-6-glucuronide and from 20% to 49%
      for morphine-3-glucuronide. The normalised plasma concentrations of morphine and
      its glucuronides did not increase with dose or time, and no explanation for the
      pronounced pharmacokinetic intraindividual variability was found. CONCLUSION:
      During subcutaneous infusion of morphine, there is a large intra- and
      interindividual variability of the morphine disposition which could be of
      clinical relevance.

PMID- 9516032
TI  - Myocardial amiodarone concentrations after short- and long-term treatment in
      patients with end-stage heart failure.
AB  - BACKGROUND: Pharmacokinetics and tissue concentrations of amiodarone may vary
      considerably in end-stage heart failure, but may be crucial for treatment
      efficiency and antiarrhythmic drug therapy. OBJECTIVE: This study was undertaken
      to determine plasma amiodarone and desethylamiodarone concentrations and to
      determine whether they correlate with myocardial concentrations in explanted
      hearts from patients with end-stage heart failure. PATIENTS AND METHODS: Eight
      patients with idiopathic dilated cardiomyopathy and normal coronary arteries were
      included in the present study. Myocardial tissue samples (seven sites) and
      epicardial fat were taken from each explanted heart, and drug concentrations of
      amiodarone and desethylamiodarone were determined. In addition, plasma drug
      levels were measured and compared with the myocardial
      amiodarone/desethylamiodarone concentrations. RESULTS: The mean cumulative
      amiodarone dose was 91 g and the mean plasma concentrations of amiodarone and
      desethylamiodarone were 0.68 and 0.84 microg.ml(-1), respectively. The tissue
      concentrations of amiodarone amounted to 13.2 and 28.3 microg.g(-1),
      respectively, in the atria and to 13.0 and 40.8 microg.g(-1), respectively, in
      the ventricles. The distribution of the drug and its metabolite were similar in
      the right and left ventricles. There was a good correlation between myocardial
      concentration of amiodarone and desethylamiodarone and the cumulative ingested
      dose of amiodarone. Tissue drug concentrations correlated only poorly with plasma
      amiodarone or desethylamiodarone levels. The highest drug levels were measured in
      the epicardial fat tissue, where the ratio of amiodarone 105 microg.g(-1) to
      desethylamiodarone 32 microg.g(-1) was reversed (3.3 compared with 0.29 in the
      ventricles). Thus, amiodarone concentrations in epicardial fat were approximately
      10 times higher than myocardial and 150 times higher than plasma levels.
      CONCLUSIONS: Our data confirm the slow equilibrium of amiodarone and
      desethylamiodarone concentrations between plasma and myocardium. Myocardial
      tissue concentrations of desethylamiodarone and, to a lesser degree, amiodarone
      correlate with the cumulative ingested dose of amiodarone. Monitoring of the
      total cumulative dose may be more relevant clinically than monitoring plasma
      levels. These results support the clinical practice of reducing the maintenance
      dose of amiodarone in patients who are on long-term treatment.

PMID- 9516033
TI  - Determination of population pharmacokinetic parameters for amikacin in neonates
      using mixed-effect models.
AB  - OBJECTIVE: The population pharmacokinetics of amikacin, in neonates, was
      investigated using the nonlinear mixed effects model (NONMEM). METHODS: One
      hundred and six steady-state amikacin serum levels were obtained from 53 black
      neonates with a mean gestational age of 35.1 weeks and mean age at the start of
      treatment of 3.1 days. A one-compartment model was used to fit the data. RESULTS:
      The final models for clearance (CL) and volume of distribution (V) were: CL(l.h(
      1)) = 0.031WT(1.45) x P and V(l) = 0.316WT(1.44) where WT = birth weight (kg) and
      P = 1.28 for girls and 1.0 for boys. Inclusion of other fixed effect parameters
      in the model did not significantly improve the fit of the data. The inter
      individual variability for CL and V were 18% and 13%. respectively. Intra
      individual variability was 29%. Mean (95% CI) values of CL, V and half-life were
      0.048 (0.045, 0.051) l.h(-1).kg(-1), 0.434 (0.414, 0.453) l.kg(-1) and 6.4 (6.2,
      6.6) h respectively. CONCLUSION: Birth weight was an important determinant of
      both CL and V and, in this data set, gender was also found to influence CL. Mean
      population pharmacokinetic values were within the range of those previously
      derived for other neonatal populations using traditional methods.

PMID- 9516034
TI  - Changes in urinary 6beta-hydroxycortisol/cortisol ratio after birth in human
      neonates.
AB  - OBJECTIVE: Urinary 6beta-hydroxycortisol/cortisol (6beta-OHF/C) ratio was
      measured in human neonates to assess the CYP3A enzyme activity. METHODS: Urinary
      6beta-OHF/C ratio was determined on the day of birth in 94 neonates including
      those born prematurely. In addition, changes in the ratios after birth were also
      determined in 81 neonates. RESULTS: On the day of birth, a significant positive
      correlation was found between urinary 6beta-OHF/C ratios and gestational age (r =
      0.476) and birth weight (r = 0.283). There was no gender difference in the
      urinary 6beta-OHF/C ratios in human neonates. Furthermore, delivery modes such as
      cesarean section and vaginal delivery did not appear to affect the urinary 6beta
      OHF/C ratio. The mean ratio of urinary 6beta-OHF/C observed in 39 mature neonates
      (more than 37 weeks of gestational age) was higher than that observed in adults
      (16.5 vs 9.9). Within 5 days after birth, the ratio rapidly decreased to less
      than that in adults. In contrast, the mean ratio of urinary 6beta-OHF/C observed
      in 42 premature neonates (under 37 weeks of gestational age) was significantly
      lower than that observed in mature neonates (5.3 vs 16.5) and was virtually
      unchanged during the 14-days after birth. Therefore, no significant difference
      was observed in the mean ratio of urinary 6beta-OHF/C between mature and
      premature neonates at 5 days after birth. CONCLUSION: From these results, it was
      concluded that on the day of birth, mature neonates might possess a higher
      activity of CYP3A enzyme compared with premature neonates, and that the CYP3A
      enzyme activity in mature neonates might be promptly changed at an early stage
      after birth.

PMID- 9516035
TI  - Correlation between steady-state plasma concentrations of mianserin and trazodone
      in depressed patients.
AB  - OBJECTIVE: The correlations between steady-state plasma concentrations of
      mianserin and its active metabolite desmethylmianserin and those of trazodone and
      its active metabolite m-chlorophenylpiperazine (m-CPP) were examined in 19
      depressed patients. METHODS: Ten patients received first mianserin (30 mg per
      day) and second trazodone (150 mg per day), while 9 patients received these
      treatments in the opposite sequence, with at least 2-week intervals between the
      two phases. Blood was sampled at steady state, 1-3 weeks after initiation of each
      treatment. Plasma concentrations of mianserin, the separate enantiomers S(+)- and
      R(-)-mianserin, desmethylmianserin, trazodone and m-CPP were measured by means of
      high-performance liquid chromatography. RESULTS: There was a significant
      correlation between steady-state plasma concentrations of trazodone and total
      mianserin (r = 0.59) or S(+)-mianserin (r = 0.57), but not R(-)-mianserin (r =
      0.33). CONCLUSION: The present study thus suggests that the metabolic capacity of
      mianserin, especially the more active S(+)-enantiomer, and that of trazodone
      correlate to each other. This finding supports the previous suggestions that
      cytochrome P4502D6 is involved in the metabolism of mianserin and trazodone.

PMID- 9516036
TI  - The pharmacokinetics of oxybutynin is unaffected by gender and contraceptive
      steroids.
AB  - OBJECTIVE AND METHODS: The effect of gender and concomitant use of contraceptive
      steroids on the absorption and metabolism of oxybutynin was investigated in 49
      healthy volunteers, 24 females and 25 males. Serum concentrations of oxybutynin
      and its active metabolite, N-desethyloxybutynin, were measured for up to 48 h
      after ingestion of a single dose of 10 mg oxybutynin. RESULTS: Intake of oral
      contraceptive steroids had no significant effect on the pharmacokinetic
      parameters of oxybutynin or its metabolite. Both in males and females, the mean
      area under the curve (AUC0-t) of N-desethyloxybutynin was about 13 times higher
      and the peak concentration (Cmax) 15 to 19 times higher than the AUC0-t and Cmax
      of the parent oxybutynin, with no significant differences between males and
      females. CONCLUSIONS: The pharmacokinetics of orally administered oxybutynin
      shows a considerable interindividual variability, but is unaffected by gender and
      use of contraceptive steroids.

PMID- 9516037
TI  - Intraindividual variability of paracetamol absorption kinetics after a semi-solid
      meal in healthy volunteers.
AB  - OBJECTIVE: The absorption kinetics of paracetamol is dependent on gastric
      emptying and its measurement was proposed as a non-invasive method to estimate
      gastric emptying rate. The objective of this study was to evaluate the
      intraindividual variability of paracetamol absorption kinetics after a semi-solid
      meal. METHODS: The pharmacokinetics of paracetamol was studied on two occasions
      in 15 healthy volunteers without Helicobacter pylori antibodies. A 1-g dose of
      paracetamol was given as a solution together with a standardised semi-solid meal
      and the subjects stayed in the supine position. RESULTS: For most of the
      subjects, the time course of paracetamol concentrations was similar on the two
      occasions. The intraindividual variability was low, with coefficients of
      variation of 38.3%, 8.0% and 3.8% for time to maximum plasma concentration,
      maximum concentration and area under the plasma concentration - time curve until
      6 h, respectively. CONCLUSION: The assessment of paracetamol absorption kinetics
      is reproducible when the drug is given together with a semi-solid meal in
      Helicobacter pylori-negative healthy subjects.

PMID- 9516038
TI  - A distribution study of CYP1A2 phenotypes among smokers and non-smokers in a
      cohort of healthy Caucasian volunteers.
AB  - OBJECTIVE: To analyse distributions of a urinary ratio of caffeine metabolites
      (MRc) representative of cytochrome P450 (CYP) 1A2 activity in a cohort of
      Caucasian German healthy volunteers and to re-assess the effects of smoking and
      oral contraceptives on the range and type of MRc distribution. METHODS: A cohort
      of volunteers comprising 192 individuals (96 males, 96 females) was divided into
      subgroups according to smoking and/or use of oral contraceptives. The CYP1A2
      substrate caffeine was administered, and urine was collected for 6 h and analysed
      for representative caffeine metabolites. Distribution of a CYP1A2-dependent MRc
      was analysed using cumulative distribution (probit) plots and Rosin-Rammler
      Sperling-Weibull (RRSW) functions. RESULTS: Cumulative distribution curves for
      males, and females, without further subgrouping for smoking habits and/or oral
      contraceptive steroid (OCS) consumption, showed slightly higher MRc values, i.e.
      slightly higher CYP1A2 activities, in males. Significantly higher MRc values were
      found in smokers of both sexes than in non-smokers. The distributions among
      female non-smokers or smokers with and without OCS were nearly super-imposible,
      however. For the two male subgroups, the sum of two RRSW functions resulted in a
      better adjustment to the data than a unimodal skewed distribution. A weak
      correlation between MRc and the number of cigarettes smoked per day was found.
      CONCLUSION: The inducing effect of smoking on CYP1A2 activity was confirmed,
      whereas no significant inhibitory effect of oral contraceptives was observed. The
      finding that the data are compatible with bimodal distributions in non-smokers
      suggests a significant impact of genetic factors on MRc. Among smokers, data were
      also compatible with bimodal distributions, i.e. with the existence of a "non
      responder" phenotype concerning CYP1A2 induction by compounds present in tobacco
      smoke.

PMID- 9516039
TI  - Company observational post-marketing studies: drug risk assessment and drug
      research in special populations--a study-based analysis.
AB  - OBJECTIVES: Company observational post-marketing studies (COPS) claim to provide
      essential data about drug risks and effectiveness in special populations not
      admitted to pre-approval clinical trials. Since COPS are often mainly regarded as
      a marketing activity, this study-based analysis tries to evaluate the scientific
      contributions of COPS. MATERIAL AND METHODS: Thirty-five COPS were identified by
      hand-searching through medical journals, writing to pharmaceutical manufacturers
      and using MEDLINE. Fourteen COPS evaluated cardiovascular drugs, 9 evaluated
      NSAIDs and 12 evaluated various other indications. RESULTS: Thirty-five COPS
      listed effectiveness, 31 listed safety and 8 listed patient compliance as
      principal objectives. Not a single COPS included a control group. Seventeen of 21
      evaluable COPS mentioned extensive exclusion criteria similar to those in
      clinical trials. Median observation time was 8 weeks, too short for chronic
      diseases and for adverse drug reactions with longer latency periods. One new
      adverse event was regarded. Global assessments of the outcomes by physicians
      dominated and were not based on objective clinical findings. None of the studies
      specified any details concerning the standardisation of observations or quality
      control procedures. DISCUSSION AND CONCLUSION: The current COPS scheme does not
      contribute significantly to our knowledge of drug safety and the effects in
      special populations. Despite serious criticism over the past 20 years, the poor
      quality of COPS compared with dramatic improvements of pre-approval trials -
      implies a need for detailed guidelines for non-experimental phase IV research,
      similar to the Good Clinical Practice-Guideline of the European Community.

PMID- 9516040
TI  - Estimation of drug concentrations in plasma from urinary excretion data: an
      illustration based on salbutamol.

PMID- 9516041
TI  - Pharmacokinetic and bioequivalence evaluation of two generic formulations of oral
      artesunate.

PMID- 9516042
TI  - Alzheimer's beta-amyloid peptide: affinity for metal chelates.
AB  - Alzheimer's amyloid peptide, A beta(1-42) and its fragments, A beta(1-28) and A
      beta(1-16), were chromatographed on IDA-M(II) columns (M: Cu2+, Ni2+ and Zn2+).
      The retention of A beta(1-42) and its fragments on IDA-Cu(II) could not be
      reversed in decreasing a gradient of pH, from 7.0 to 4.0. All A beta peptides
      were recovered from IDA-Ni(II) columns in a decreasing pH gradient from 7.0 to
      4.0, within the pH range from 5.6 to 5.1. A beta(1-42) peptide was strongly
      retained on IDA-Zn(II) at pH 4.0, but its A beta(1-28) and A beta(1-16) were only
      transiently retained on IDA-Zn(II) columns when applied at pH 6.1. We submit that
      histidine clusters, residing both in the Alzheimer's beta-amyloid peptide and in
      most of the APP/APLP superfamily of proteins, constitute high-affinity binding
      sites for immobilized metal chelates.

PMID- 9516043
TI  - UV-difference and CD spectroscopy studies on juvenile hormone binding to its
      carrier protein.
AB  - Juvenile hormone binding protein (JHBP) from hemolymph of Galleria mellonella is
      a single-chain glycoprotein of molecular mass near 25,880 containing no Trp
      residues. The fourth derivative of the protein absorption spectrum shows the
      characteristic vibrational components of the phenylalanine spectrum within the
      range 240-270 nm. At longer wavelengths two main bands 0-0 and 0+800 cm(-1)
      appear, caused by vibrational levels of electronic transition, pi-->pi*, in the
      tyrosine residues, with maxima at 279 nm and 286 nm, respectively. Two
      intersection points of the second derivative absorption band with abscissa at
      about 288.8 nm and 283 nm were analysed for estimation of the environment
      polarity of Tyr residues in the JHBP molecule. The results obtained suggest that
      JHBP contains at least two classes of Tyr residues with very apolar environment,
      similar to that found in azurine. In the JHBP-JH complex only one class of Tyr
      residues located in a very apolar environment was found, and a small perturbation
      of disulphide bridges was deduced from the UV-difference spectrum. Ligand
      perturbation appears as a minimum at 243 nm of the UV-difference spectrum.
      Comparison of the circular dichroism (CD) spectra for free JHBP with the CD
      spectra for the JHBP-JH complex monitored in the far-UV (190-240 nm) region
      indicates rather small differences in the secondary structure of the protein.
      Although ligand binding induces distinct changes in the near-UV (250-300 nm)
      region of the CD spectrum of JHBP, it is apparent where both Tyr and Phe residues
      contribute.

PMID- 9516044
TI  - Interaction of alpha-helical peptides with phospholipid membrane: effects of
      chain length and hydrophobicity of peptides.
AB  - To investigate the interaction of amphiphilic alpha-helical peptides with
      phospholipid membranes, we synthesized Ac-(Leu-Ala-Arg-Leu)3-NHCH3 (4[3]) and
      three derivatives, in which the chain length and the size of the hydrophobic
      region of the peptides were different from each other. These peptides formed an
      alpha-helical structure in the presence of vesicles. In the membrane-perturbation
      measurement, only 43 showed a strong membrane-perturbation activity below phase
      transition temperature (25 degrees C), but above phase-transition temperature (50
      degrees C), most peptides showed similar strong activities. On the other hand, in
      membrane-fusion measurement the long peptides, e.g., Ac-(Leu-Ala-Arg-Leu)3-(Leu
      Arg-Ala-Leu)3-NHCH3, had strong activities at low peptide concentrations at 25
      degrees C. The present study indicated a parallel relationship did not always
      exist between membrane fusion and perturbation caused by peptides.

PMID- 9516045
TI  - Design, synthesis and CD4 binding studies of a fluorescent analogue of a peptide
      that enhances HIV-1 infectivity.
AB  - We previously demonstrated that a 23-amino-acid peptide derived from the V3 loop
      of the surface glycoprotein of human immunodeficiency virus (HIV-1) strain MN was
      able to bind soluble CD4 and to enhance HIV-1 infection. Further studies
      suggested that the peptide/CD4 interaction induces an increase in both CD4
      expression and CD4/gp120 binding affinity. To facilitate identification of the
      complementary binding site for the peptide on cellular CD4, we designed an
      analogue carrying a single fluorescein moiety. The synthesis of this modified
      analogue presented several problems because of the presence of several amino
      acids in the sequence carrying potentially reactive groups in their side-chains,
      and the necessity of introducing only one marker per molecule in a position that
      would not affect biological activity. The side-chain of Lys19 was selected
      because separate studies demonstrated that its substitution with an uncharged
      amino acid does not reduce the peptide's biological activity. We compared the
      merits of various synthetic protocols used to condense the fluorescent marker
      with the peptide. Biological assays indicated that the presence of the
      fluorescein moiety did not compromise peptide binding to CD4; furthermore,
      binding of the labeled analogue was not abolished by trypsin treatment,
      suggesting that the peptide may interact with both CD4 and additional trypsin
      resistant binding sites on the cell surface. Finally, we verified the
      preservation of HIV infection enhancing ability in the labeled peptide.

PMID- 9516046
TI  - Synthesis and conformational analysis of two 2-oxopiperazine-containing
      tetrapeptide analogues.
AB  - One unsubstituted and one stereoselectively prepared 3-(S)-substituted-2
      oxopiperazine have been used as dipeptide templates to generate tetrapeptide
      analogues. NMR analysis shows that these tetrapeptide analogues present an
      inverse gamma-turn conformation in chloroform.

PMID- 9516048
TI  - Investigation on the stability of the Dde protecting group used in peptide
      synthesis: migration to an unprotected lysine.
AB  - An investigation of the stability of the Dde protecting group for amines, used in
      solid-phase peptide synthesis, shows that an unprotected epsilon-NH2 group of
      lysine can acquire the Dde protection from another epsilon-NH2 group or from an
      alpha-NH2 group. An unprotected alpha-NH2, however, cannot remove Dde from an
      epsilon-NH2 function. This migration takes place during Fmoc removal from the
      epsilon-NH2 with piperidine and/or during the subsequent washing steps. The Dde
      migration is also possible in neat dimethylformamide by a direct nucleophilic
      attack of the free epsilon-NH2 group. Addition of piperidine to the reaction
      medium accelerates the side reaction, probably because of the formation of an
      unstable piperidine-Dde adduct. Dde migration can be prevented if the 9
      fluorenylmethyloxycarbonyl is cleaved with 1,8-diazabicyclo[5.4.0]undec-7-ene for
      a short reaction time (2%, 3 x 3 min). Finally, this rearrangement is shown to
      occur both as an intra- and intermolecular reaction between peptides on the same
      resin bead.

PMID- 9516049
TI  - New analogs of human growth hormone-releasing hormone (1-29) with high and
      prolonged antagonistic activity.
AB  - Based on our previous results, in conjunction with various structural
      considerations, 19 new analogs of the GHRH antagonist [PhAc-Tyr1,D
      Arg2,Phe(pCl)6,Abu15,Nle27,Agm29]++ +hGHRH(1-29) (MZ-5-156) were synthesized by
      the solid-phase method. These compounds were designed to develop further analogs
      of this class with increased receptor-binding affinity. All analogs had Abu15 and
      Nle27 modifications and were acylated with phenylacetic acid at the N-terminus.
      Most of the analogs had D-Arg2 and Phe(pCl)6 substituents and Agm29 or Arg29-NH2
      at the C-terminus. Additional single substitutions consisted of the incorporation
      of D- or L-Tic1, D-Tic2, Tic6 or Phe(pNO2)6 and Arg29-NH2. The Arg29-NH2 analog
      of MZ-5-156 (KT-48) was further modified by single substitutions using Pal1; D
      Tpi2; D- or L-Phe4; Phe(pX)6 X = F, Cl, I; Tyr7; Aib8; Tyr(Me)10 or Phe(pCl)10.
      Four peptides had multiple substitutions. All the analogs were evaluated for
      their ability to inhibit GH release induced by hGHRH(1-29)NH2 in vitro and some
      were also tested in vivo. Peptides [PhAc-Tyr1,D-Arg2,Phe(pI)6,Abu15,Nle27]hGHRH(1
      2 9)NH2 (KT-30), [PhAc-Tyr1,D-Arg2,Phe(pCl)6,Aib8,Abu15,Nle27] hGHRH(1-29)NH2 (KT
      50) and [PhAc-Tyr1,D-Arg2,Phe(pCl)6,Tyr(Me)10,Abu15,Nle27]h GHRH(1-29)NH2 (KT-40)
      with Phe(pI)6, Aib8 or Tyr(Me)10 modifications, respectively, showed high and
      prolonged inhibitory effect in superfused rat pituitary system. Analog KT-50 also
      exhibited a strong and long-term inhibitory activity in vivo in rats. Most of the
      new analogs showed high binding affinities to rat pituitary GHRH receptors.

PMID- 9516047
TI  - New antibiotic caerin 1 peptides from the skin secretion of the Australian tree
      frog Litoria chloris. Comparison of the activities of the caerin 1 peptides from
      the genus Litoria.
AB  - The skin glands of the tree frog Litoria chloris contain a variety of peptides
      including four antibacterial peptides of the caerin 1 family. Two of these,
      caerins 1.6 and 1.7, are also present in the related species Litoria xanthomera.
      The other two peptides, caerins 1.8 and 1.9, are new. Their sequences are:
      GLFKVLGSVAKHLLPHVVPVIAEKL-NH2 [Caerin 1.8] and GLFGVLGSIAKHVLPHVVPVIAEKL-NH2
      [Caerin 1.9]. Comparison of the skin peptide profiles of L. chloris and L.
      xanthomera confirms that these species are more closely related to each other
      than to any other species of the genus Litoria that we have studied. A comparison
      is made of the antibiotic activities of nine members of the caerin 1 family of
      peptides isolated from tree frogs of the genus Litoria.

PMID- 9516050
TI  - Biologically active analogues of arginine vasopressin containing conformationally
      restricted dipeptide fragments.
AB  - In this study we described the synthesis and pharmacological properties of five
      new analogues of arginine vasopressin (AVP). Four of these analogues contained
      ethylene-bridged dipeptide Phe-Phe in positions 2 and 3; one had two N-Me-Phe
      residues. All new peptides were tested for vasopressor and antidiuretic
      activities. We also estimated the uterotonic activities of these compounds in
      vitro. Three analogues were highly potent V1-antagonists. One of them, namely
      [Cpa1,(Phe-Phe)2,3,Val4]AVP, which seemed to not interact with either V2 and
      oxytocic receptors, was outstandingly selective. It is interesting that the high
      antipressor potency of our second peptide, [(N-Me-Phe)2,3]AVP, was achieved
      without modification of position 1. Our results open new possibilities for the
      design of very potent and selective V1-antagonists of AVP.

PMID- 9516052
TI  - Alpha-(Ac)AKRHRKV, a model of the histone H4 amino terminus, uses an unprotonated
      histidine in phosphate binding.
AB  - The 1H NMR spectrum of the title peptide at pH 3.3 in 90% H2O was assigned by
      HOHAHA and NOESY 2D methods. Titration studies in D2O at 300 MHz indicated a
      histidine side-chain pKa of 6.3. Peptide backbone NH resonances were studied in
      90% H2O at 500 MHz as a function of pH and added phosphate. In acidic solution
      the peptide was free from conventional secondary structural elements, but near
      neutrality the valine amide proton resonance remained a sharp doublet, which
      suggests that it may form a hydrogen bond with some backbone carbonyl group. The
      other amide resonances broadened and showed significant saturation transfer from
      the water signal indicating that they exchange with solvent although not all to
      the same extent. Marked changes in the chemical shift of the histidine aromatic
      protons in the presence of phosphate and a 70-fold increase in the 31P line width
      of inorganic phosphate in the presence of peptide only at pH values above the pKa
      (6.3) of the histidine imidazole side-chain implied that the unprotonated
      imidazole group is specifically involved in phosphate binding. The peptide binds
      inorganic phosphate with a dissociation constant of 1.6 x 10(-5) M(-1) at pH 7.4.

PMID- 9516051
TI  - Structural studies on endothelin receptor subtype B specific agonist IRL 1620
      [suc-[Glu9, Ala11,15]ET-1(8-21)] and its analogs with dipalmitoyl
      phosphatidylcholine vesicles by NMR spectroscopy.
AB  - IRL 1620 ?suc-[Glu9,Ala11,15]ET-1(8-21)? is a potent and specific agonist for the
      ET(B) receptor. Five analogs of IRL 1620 were synthesized in this study. These
      were all C-terminal linear peptides of endothelin 1 (ET-1) comprising 14 amino
      acid residues and exhibiting highly potent ET(B) receptor binding affinities. The
      peptides consisted of three pairs and each component of the pairs differed from
      its partner in only the 18th residue, i.e. Asp was replaced by Gly. The
      replacements resulted in more than a 10-fold increase in affinity to the ET(A)
      receptor. The structures of these peptides were investigated in the presence of
      phospholipid vesicles (dipalmitoyl phosphatidylcholine) by NMR spectroscopy. By
      the replacement of Asp by a less bulky Gly, the C-terminal tripeptide region
      folded back toward the helical region, making it shorter than the Asp-substituted
      peptide helical region. Such a folded conformational feature may explain the
      increased binding affinity to ET(A) receptor.

PMID- 9516053
TI  - To be lean or not to be lean. Is leptin the answer?
AB  - Leptin and the leptin receptor genes have been identified as the site of
      mutations in the peripheral adipocyte hormone pathway responsible for obesity in
      the ob/ob mouse (Zhang et al., 1994) and the db/db mouse (Chen et al., 1996). In
      obese humans, ob/ob like mutations in leptin are rare but confirm a role for
      leptin (Montague et al., 1997), and db/db like mutations in the leptin receptor
      have not been found (Considine et al., 1996a); however, the increased
      understanding of the molecular basis for obesity has generated tremendous
      interest among scientists and patients alike. The new knowledge could be the base
      for intelligent drugs for the treatment of obesity. Herein we will put in
      perspective a) the physiological background that led to the discovery of leptin,
      b) leptin biosynthesis, c) leptin action and d) the clinical issues related to
      leptin as a drug for the treatment of obesity.

PMID- 9516054
TI  - Heart disease in diabetes mellitus: a challenge for early diagnosis and
      intervention.
AB  - Most people with diabetes die from thrombotic complications superimposed to
      degenerative arterial vascular lesions, mostly myocardial infarction. Diabetes is
      a risk factor per se for such complications, but often clusters with
      dyslipoproteinemia, hypertension and obesity. In NIDDM (Type-II) patients this is
      referred to as "metabolic syndrome" and often operates on a genetically
      programmed susceptibility which accelerates the pathogenesis of coronary artery
      disease in front of a much wider diabetes specific cardiopathy. From a
      pathophysiological point of view none of these associated risk factors explains
      the pathogenetic series of events leading to the precipitation of an occlusive
      thrombus at sites of complicated coronary plaques. In patients with diabetes the
      coagulation system is switched towards a prethrombotic state, involving increased
      plasmatic coagulation, diminished fibrinolysis, decreased endothelial
      thromboresistance and predominantly platelet hyperreactivity ("diabetic
      thrombocytopathy"). Some of these factors are associated with an increased
      coronary risk (e.g. fibrinogen, PAI-1, platelets), but are also directly linked
      to the pathogenesis of "atherothrombosis". Altered cardiac remodelling together
      with adhesion and coagulation mechanisms appears suitable to explain decreased
      functional performance of infarcted organs, decreased success of acute (reduced
      fibrinolytic response, reperfusion injury) and longterm intervention strategies
      (PTCA, CABG) in diabetes. Glucose adjustment alone will not adequately neutralize
      these complex mechanisms. Particularly in diabetes a multidimensional
      interventional repertoire is required including antihypertensive,
      antidyslipoproteinemic and antithrombotic drugs, customized according to the
      individual patients needs as assessed by early diagnostic measures ("early
      secondary prevention").

PMID- 9516056
TI  - Prophylactic thyroidectomy, based on direct genetic testing, in patients at risk
      for the multiple endocrine neoplasia type 2 syndromes.
AB  - Since the discovery that germ-line mutations in the RET protooncogene are
      responsible for the multiple endocrine neoplasia (MEN) syndromes types 2A and 2B,
      prophylactic thyroidectomy has been recommended for MEN patients to prevent
      medullary thyroid carcinoma (MTC). In this report, we present the medium-term
      follow up results on the earliest group of 18 patients having prophylactic
      thyroidectomy for MEN 2A. There were no operative complications. Microscopic or
      grossly evident MTC was present in 14 (78%) of the resected patients. None of the
      patients had metastasis of their MTC to regional lymph nodes. At three years'
      follow up, there is no evidence of residual or recurrent MTC, based on
      biochemical testing. We conclude that prophylactic thyroidectomy, based on direct
      DNA testing for RET gene mutations, is an effective and safe way to manage MTC in
      patients with MEN 2A.

PMID- 9516055
TI  - Biological actions of glucagon-like peptide(GLP)-2 revealed--how pluripotential
      is the glucagon gene?
AB  - Recently published data from the group of Drucker indicate that glucagon-like
      peptide (GLP)-2 induces intestinal epithelial proliferation. This is the first
      biological effect assigned to this proglucagon-derived peptide (PGDP) and
      represents, perhaps, the most convincing evidence, so far, to support the
      existing hypothesis that PGDPs can act to promote intestinal epithelial growth
      and adaptation. Also, these findings prompt certain clinical considerations.
      Here, we summarise the reported effects of GLP-2 and highlight the important
      questions which need to be addressed with special reference to the clinical
      implications.

PMID- 9516057
TI  - Macrovascular disease of coronaries and cerebral arteries in streptozotocin
      induced diabetic rats. A controlled, comparative study.
AB  - The aim of this study was to demonstrate the macrovascular disease in
      streptozotocin-induced diabetic rats and assess any possible differences between
      the histopatholological changes of the coronaries and cerebral arteries. Hearts
      and brains were obtained after 4 weeks (short-term experimental diabetes, 10
      rats) and 12 weeks (long-term experimental diabetes, 10 rats) of streptozotocin
      injection. Sham injected, control rats were studied in parallel. Muscular-type
      arteries of 0.10-0.15 mm were examined and semiquantitatively classified either
      as normal, or slightly, or moderately, or severely thickened by light microscopy:
      While the arterial wall appeared normal in all sham-injected rats, a varying
      degree of hyperplasia of the muscular layer and deposition of fibrinoid material
      resulting in arterial stenosis was prominent in streptozotocin-injected rats. In
      the group of short-term diabetes there was a slight thickening of the cerebral
      arteries in the majority of the rats (8/10 rats), while thickening of the
      coronaries was moderate (9/10 rats). Further progression of arterial wall
      thickening in both cerebral and coronary arteries was observed in the long-term
      diabetic group. The mean severity of lesions was significantly higher in the
      coronaries than in cerebral arteries, both in the short-term (p < 0.0005) and
      long-term diabetes (p < 0.02). Moreover, by paired statistics within individual
      animals, we confirmed that wall thickening was significantly more severe in
      coronaries than cerebral arteries in both groups. These findings suggest an
      accelerated progress of macrovascular disease in the heart as compared to the
      brain in the streptozotocin-induced diabetic rat. Although histopathological
      changes in humans do not always mirror clinical severity, the differences in the
      macrovascular disease between heart and brain in experimental diabetes may be
      relevant to the higher relative risk of myocardial infarction compared to stroke
      for people with diabetes, as compared to people without diabetes.

PMID- 9516058
TI  - Concentrations of circulating P-selectin are increased in patients with newly
      diagnosed insulin-dependent diabetes mellitus.
AB  - Endothelial cell activations and/or dysregulations of the coagulation system are
      crucial parameters for the prognosis of disease in patients with IDDM. Recent
      data suggest that expression of the adhesion molecules E-selectin and P-selectin
      are markers of endothelial cell activation and/or platelet activation and might
      modify immunologic responses after shedding from cell membranes. In patients with
      newly diagnosed IDDM only limited data on circulating selectins are available.
      This has prompted us to measure levels of soluble (s) forms of P-selectin and E
      selectin in 18 patients with newly diagnosed IDDM and two years after the onset
      of insulin substitution therapy in comparison to 18 age-matched healthy control
      subjects. HbA1c and blood glucose levels were significantly higher in patients
      with new onset diabetes, compared to the same patients after two years of insulin
      therapy (HbA1c: 12 +/- 3% vs. 7.8 +/- 2%; p < 0.01; blood-glucose: 409 +/- 163
      mg/dl vs. 131 +/- 23 mg/dl; p < 0.01), but no correlation between these metabolic
      parameters and soluble forms of E- and P-selectins were noted. Levels of sP
      selectin decreased from 210 +/- 120 ng/ml in newly diagnosed IDDM patients to 127
      +/- 75 ng/ml after two years of therapy (p < 0.01) and were similar to those of
      the control subjects (110 +/- 31 ng/ml). Serum concentrations of circulating E
      selectin showed no differences in the three groups (newly diagnosed IDDM: 42 +/-
      17 ng/ml; two years later: 43 +/- 19 ng/ml; control subjects: 41 +/- 14 ng/ml;
      n.s.). Increased levels of sP-selectin together with normal levels of sE-selectin
      at the onset of IDDM suggest enhanced platelet activation during the initial
      phase of the autoimmune process and return to baseline levels within two years of
      the disease.

PMID- 9516059
TI  - Microcirculation in hyperglycemic patients with IDDM without diabetic
      complications--effect of low-dose angiotensin-converting enzyme inhibition.
AB  - In patients with insulin-dependent diabetes mellitus (IDDM) angiotensin
      converting enzyme inhibitors (ACEI) have been demonstrated to have beneficial
      effects in the secondary prevention of microvascular complications. There are
      only few data available regarding the effect of ACEI on microcirculation in
      patients with IDDM without any microvascular complications. In addition, there is
      little knowledge about ACEI action during acute hyperglycemia. In a pilot study
      nine patients with IDDM without any clinical signs of diabetic complications (5
      females, 4 males, aged 33.3 +/- 1.0 years, duration of diabetes 11.4 +/- 3.0
      years, HbA1 7.2 +/- 0.2% [normal range 4.8-7.4%], BMI 21.4 +/- 0.5 [kg/m2])
      received 1.25 mg of the ACEI ramipril (Delix, Hoechst Marion Roussel, Frankfurt)
      over 4 weeks. Nine healthy volunteers (4 females, 5 males, age 27.4 +/- 1.1
      years, HbA1 5.9 +/- 0.2% (p < 0.01 vs patients), BMI 22.2 +/- 0.9 [kg/m2]) served
      as controls. Using nailfold capillaroscopy we determined capillary blood cell
      velocity (CapiFlow, Lawrenz Electronics, Sulzbach, Germany) before and during
      post-occlusive hyperemia (200 mmHg for 3 minutes) as a provocative test. Before
      and after treatment patients were studied during hyperglycemia (blood glucose 250
      350 mg/dl). Treatment with low-dose ramipril resulted in a significant decrease
      in the time to peak capillary blood cell velocity during post-occlusive hyperemia
      (17.8 +/- 7.7 vs 57.4 +/- 12.8 s, p < 0.01) in hyperglycemic patients. This
      effect was absent in healthy volunteers. Hemodynamic and metabolic parameters
      remained unchanged throughout the study in both groups. These data demonstrate
      that low-dose therapy with the ACEI ramipril is able to improve microcirculation
      in hyperglycemic patients with type 1 diabetes mellitus also before microvascular
      complications are evident. Prospective studies are necessary to evaluate whether
      this effect might be clinically relevant in the primary prevention of diabetic
      microangiopathy.

PMID- 9516060
TI  - Longitudinal study of urinary hydroxy-pyridinium cross-links and growth in
      healthy infants: higher values with breastfeeding and after daytime sleep.
AB  - Urinary pyridinoline and deoxypyridinoline crosslinks (crosslink) are excreted
      when bone is resorbed. The aims of this study in healthy infants were to
      determine whether crosslinks a) could predict growth velocity, b) are variable
      due to circadian rhythm, and c) differ in infants who were either breast-fed or
      formula-fed. In 78 healthy infants (48 male; 30 female) urine samples were
      collected and anthropometric measurements were taken at 2, 3, 4, 5, 6, 8, 10 and
      12 months of age. In addition, a total of 25 samples were collected during the
      day (0700-2000) in 5 of the infants to determine circadian rhythm of crosslink
      excretion. Crosslink excretion decreased (p < 0.001) with age between 2 and 12
      months. Pyridinoline excretion showed a significant, but weak correlation (r > or
      = 0.21; p < 0.05) with linear growth velocity and weight velocity in the
      subsequent month until 6 months of age, and no correlation thereafter. Infants
      studied for circadian rhythm showed a 63% greater (p < 0.05) rate of pyridinoline
      excretion after a nap as compared to the 13-hour mean value. In a subset of
      infants whose energy intake was exclusively from breast milk (BF, n = 23) or
      formula (FF, n = 10), crosslink excretion was greater in BF infants at 3 months
      of age (p < 0.05). The correlations between crosslink excretion and growth
      parameters indicate that crosslinks may be useful as a marker of growth in infant
      populations. However sources of variation in crosslink excretion, such as
      circadian rhythm and diet may limit their utility to predict growth in an
      individual infant. These factors should be considered in future studies examining
      markers of bone turnover in infants.

PMID- 9516061
TI  - Effect of hypercortisolism and ACTH on the metabolism of cortisol.
AB  - The effects of hypercortisolemia and ACTH on the metabolism of cortisol in
      congenital adrenal hyperplasia, Cushing's syndrome, and exogenous ACTH and
      cortisol administration were investigated by analysis of the respective urinary
      tetrahydro-metabolites of cortisol (THF and aTHF) and cortisone (THE) by
      capillary gas chromatography. The results for the patients with congenital
      adrenal hyperplasia establish that ACTH hypersecretion in the absence of an
      associated marked elevation of plasma cortisol does not cause inhibition of the
      11beta-OHSD enzyme. In contrast elevated plasma cortisol levels (adrenal adenoma
      or intravenous cortisol administration) in the presence of suppressed ACTH
      secretion leads to significant inhibition of the peripheral conversion of
      cortisol to cortisone. The latter results are equivalent to the mode of cortisol
      metabolism noted during clinical states of ACTH hypersecretion and
      hypercortisolemia (Cushing's disease, ectopic ACTH syndrome and ACTH
      administration). The overall findings provide convincing evidence that ACTH
      hypersecretion is not associated with specific in vivo inhibition of 11beta-OHSD
      enzyme activity.

PMID- 9516062
TI  - Reassessment of the role of human placental lactogen in physiological non
      pregnant and pathological conditions.
AB  - The recent demonstration of ectopic production of human placental lactogen (PL)
      in the human testis and ovary prompted us to reassess its role under non-pregnant
      physiological and pathological conditions. Possible physiological hPL
      concentrations and potential age-related changes in the sera of healthy young and
      elderly individuals (n = 75) selected according to the SENIEUR-protocol were
      investigated by a highly sensitive (detection limit: 2 pg/ml) and specific (cross
      reactivity with prolactin and human growth hormone (hGH) of less than 0.001% and
      0.0001%, respectively) monoclonal antibody-based time-resolved fluoroimmunoassay
      (IFMA) established in our laboratory. All individuals, even the aged probands
      (mean age: 72 +/- 3a), had hPL-levels below 20 pg/ml, in contrast to glycoprotein
      hormones, such as luteinizing hormone or human chorionic gonadotropin (hCG). To
      determine the significance of hPL as a tumour marker, serum samples of 12
      testicular cancer patients with highly elevated levels of holo-hCG (mean: 42.490
      ng/ml) at diagnosis were followed over 6-12 months and analysed with the hPL
      IFMA. Elevation of hPL was seen in 10 patients, but the respective levels were 2
      3 orders of magnitude smaller than those of holo-hCG and returned earlier to
      undetectable values. These in vivo data were compared to the hPL secretion
      pattern of the choriocarcinoma cell lines JAR and BeWo in vitro. In tissue
      culture supernatants of the two cell lines hPL was detected only in JAR cells,
      whereas both cell lines secreted holo-hCG. In conclusion, the fact that hPL is
      not physiologically present in peripheral blood but is produced ectopically in
      the human testis and ovary suggest auto/paracrine functions of this molecule. The
      significance of hPL as a tumour marker for patients with testicular cancer is
      limited as it provides no additional information to holo-hCG.

PMID- 9516063
TI  - Growth hormone secretory response to intravenous galanin infusion in acromegalic
      patients.
AB  - Galanin is a 29-amino acid neuropeptide which stimulates the secretion of growth
      hormone (GH) in normal men. Although the diagnosis of acromegaly involves
      demonstrating hypersecretion of GH and/or abnormalities in GH secretory dynamics,
      sometimes it is difficult to establish the activity of the disease. The aim of
      our study was to assess the response to galanin infusion in acromegalic patients
      (active and cured). We studied 19 subjects: 5 healthy volunteers (group I), 9
      patients with active acromegaly (group II), and 5 with acromegaly cured after
      transsphenoidal surgery (group III). We performed a test of infusion with porcine
      galanin (8 microg/Kg/h) to study the secretory response of the GH. Galanin
      produced a marked increase in GH in the controls, group I (F9,36 = 5.34; p <
      0.01) and in the cured patients, group III (F9,36 = 7.35; p < 0.01). On the other
      hand, galanin did not significantly modify the secretion of GH in the patients
      with active disease, group II. The areas under the curve (AUC) were higher in
      groups I and III compared to group II (p < 0.01). Nevertheless, there were no
      statistically significant differences in the AUC of groups I and III. Our results
      indicate that the differences in the GH response to galanin in patients with
      active and cured acromegaly could be of value in the study of the disease.

PMID- 9516064
TI  - Zona fasciculata-like histotype and aldosterone response to upright posture are
      not related in aldosterone-producing adenomas.
AB  - Two distinct subtypes of patients with primary aldosteronism due to aldosterone
      producing adenomas (APA), based on different aldosterone responses to
      angiotensin, have been identified. We evaluated the relationship between adrenal
      zona fasciculata-like histotype and response of plasma aldosterone to upright
      posture in a series of patients with APA. Twenty-five patients were
      retrospectively divided in two groups according to aldosterone response to
      posture, i.e., a first group without postural change of aldosterone (n = 19) and
      a second group with at least 30% aldosterone increase after standing (n = 6). The
      percentage of zona fasciculata-like cells was calculated at histology in all
      adenoma tissues removed at adrenalectomy. The two groups of patients were similar
      in sex, age, systolic/diastolic blood pressure, supine/upright plasma renin
      activity, supine/upright aldosterone, tumor size. No differences between the two
      groups were observed as to zona fasciculata-like (84 +/- 3% vs 71 +/- 9%, P NS)
      and non-zona fasciculata-like cells percentage in adenoma tissues. No inverse
      correlation was found in either group between the percentage change from supine
      to upright aldosterone and the percentage of zona fasciculata-like cells.
      Aldosterone and cortisol responses to ACTH testing were similar in the two
      groups. Our results indicate that the two subtypes of primary aldosteronism based
      on different postural responses of aldosterone are not due to a different
      prevalence of zona fasciculata-like histotype in APA.

PMID- 9516065
TI  - Dysregulation of insulin-like growth factors in a case of generalized acquired
      lipoatrophic diabetes mellitus (Lawrence Syndrome) connected with autoantibodies
      against adipocyte membranes.
AB  - We report on a 33-year-old male patient with generalized acquired lipodystrophy,
      insulin resistant diabetes mellitus and acanthosis nigricans (Lawrence Syndrome).
      First probable symptoms of lipodystrophy (weight loss, shrinkage of subcutaneous
      fatty tissue, and loss of muscular strength) became evident three years ago, with
      the onset of diabetes mellitus occurring about six months later. The patient
      suffered from the following clinical symptoms: IDDM with increasing insulin
      requirement, extreme reduction of fatty tissue, fatty liver hepatitis with
      elevated liver enzymes, glomerulopathy, muscular and neuropathic pains, as well
      as hypertriglyceridaemia. A basal C-peptide concentration is rather high.
      Definitely, the endogenous insulin secretion is increased. In other words,
      insulin resistance is documented. In an effort to identify the pathogenetic
      mechanisms of lipoatrophic diabetes mellitus in this patient and to develop a
      therapeutic strategy, antibodies against different tissues and endocrinologic
      regulation were investigated. It was possible to demonstrate the presence of
      serum autoantibodies against lipocytes of the subcutis and other tissues, against
      hepatic stellate cells, together with autoantibodies against different endocrine
      organs. By studying the basis of diabetic abnormalities relating to the growth
      hormone (GH), the insulin-like growth factor (IGF) dynamics in this patient, i.e.
      reductions of GH, IGF-I, IGF-II, IGF-Binding protein (IGF-BP) 2 and IGF-BP 3,
      were detected. An immunosuppressive treatment strategy was not beneficial.

PMID- 9516066
TI  - Changes in the free (unbound) fraction of testosterone in serum in vitro as
      affected by pH and temperature.
AB  - Concomitant effects of temperature and pH on changes in the magnitude of the
      free, unbound fraction of testosterone in human serum were studied. Free fraction
      was determined by equilibrium dialysis of undiluted serum against buffer in
      microchambers at temperatures ranging from 36 to 39 degrees C and pH ranging from
      6.9 to 7.4. Free fraction increased with increasing temperature and decreasing
      pH, the two factors acting synergically. This is reflected by the fact that a
      rise in temperature from 36 to 39 degrees C causes only a slight increase in the
      free fraction at pH = 7.4 (about 7%), while at pH = 6.9 that increase is about
      35%. At 39 degrees C and pH = 6.9 the free fraction was about 1.5-fold higher
      than in standard conditions (37 degrees C, pH = 7.4). This implies that in vivo
      the free, biologically active fraction of testosterone may increase due to e.g.
      hyperthermia and acidosis at a constant total concentration of this hormone.

PMID- 9516067
TI  - Neuropeptides for neuroimmune, endocrine, developmental and pain control: new
      ligands, new receptors and the "knock out connection". 7th annual meeting of the
      European Neuropeptide Club (ENC), May 21-24, 1997, Marburg, Germany.

PMID- 9516068
TI  - Detection of cerebral aging, an absolute need: predictive value of cognitive
      status.
AB  - Cognitive performance is predictive of functional status, morbidity and mortality
      in the elderly. In the SYST-EUR study, the Vascular Dementia Project run on 3,111
      subjects 60 years old and over, with isolated systolic hypertension, has shown
      that the cognitive status as measured by the MMSE was inversely correlated with
      systolic blood pressure (p < 0.001) and age (p < 0.001) and positively correlated
      with the level of education (p < 0.001). It is significantly lower in patients
      with cardiovascular complications (p = 0.0001). Moderate alcohol consumption is
      linked to a higher MMSE score in women (p < 0.001) but not in men. In this study,
      the incidence of dementia is low and significantly related to the baseline value
      of the MMSE score and further analysis will show the influence of the treatment
      of systolic hypertension with calcium antagonists as first step on this
      incidence.

PMID- 9516069
TI  - Risk factors for cerebral degenerative changes and dementia.
AB  - It is concluded that the most important determinants for cerebral
      neurodegenerative changes and cognitive decline during aging are neuronal
      shrinkage and/or loss, which are accelerated by certain risk factors: e.g. TIAs,
      hypertension, heart disease, hyperlipidemia, smoking, heavy alcohol consumption,
      male gender, low educational status, family history of cerebrovascular disease
      and absence of estrogen replacement therapy among women. Some of these risk
      factors are remediable by therapeutic interventions, including prevention of TIAs
      and medications that control hypertension, heart disease, hyperlipidemia and
      estrogen replacement in postmenopausal women, as well as abstention from abuse of
      tobacco and alcohol. Cerebral neurodegenerative changes measured by neuroimaging
      appear to be premorbid markers for depleted neuronal and synaptic reserves which
      predispose to the onset of dementias of both VAD and DAT types. Normal subjects
      at risk for cognitive decline include those with TIAs, hypertension and heart
      disease since these risk factors measurably accelerate cerebral atrophy,
      ventricular enlargement, leukoaraiosis, and decline in cortical perfusion.

PMID- 9516070
TI  - Essential investigations of patients with suspected TIAs.
AB  - Transient ischemic attacks (TIAs) are warning episodes predicting that such
      patients are at high risk for stroke which potentially could be life-threatening
      or leave an individual with substantial disability. TIAs result from large or
      small vessel disease, cardiogenic embolic events and hematological abnormalities.
      The patient's past and current medical history provides necessary clues
      suggesting which investigational tests should be conducted. Every patient
      presenting with a TIA should have a total blood count, electrocardiogram, and a
      brain imaging study. Patients with anterior circulation symptoms should undergo
      noninvasive carotid testing, usually by carotid duplex ultrasonography, to
      determine if there is a surgically remediable carotid stenosis. Patients with
      posterior circulation TIAs should undergo magnetic resonance angiography (MRA) or
      a conventional arteriogram which, if positive, may be an indication for anti
      platelet or anticoagulation therapy. Other testing depends on the presumptive
      etiology of the TIA. In general, a TIA should be considered as a serious warning
      of impending stroke that requires rapid and efficient investigations to define
      and remedy the reasons for the cerebral ischemic events. TIAs by definition may
      last up to 24 h, but usually are self-terminating after a few minutes. They are a
      serious warning of possible future strokes that may result in substantial
      morbidity and mortality. Once TIAs are diagnosed, the major goal is to reduce the
      risk of future strokes. Patients with TIAs usually present in the Emergency Room
      or doctor's office. They may seek immediate medical care or relate the history of
      the TIA during a routine visit. As soon as a diagnosis of a TIA is considered, a
      careful past and current medical history should be taken to substantiate the
      diagnosis. Conditions which mimic TIAs need to enter into the differential
      diagnosis and, if necessary, be ruled out. For example, a Todd's transient
      paralysis can follow a partial focal seizure. Migraine auras may also mimic TIAs,
      particularly in the elderly. Any space-occupying lesions and arteriovenous
      malfunction may first present with a TIA-like complaint. Peripheral nerve disease
      must be recognized since it can cause transient weakness and/or numbness
      affecting one limb.

PMID- 9516071
TI  - A review of therapeutic potentials in ischemic stroke.
AB  - Stroke is one of the leading causes of death in the world. There are as yet no
      effective treatments for the ischemic cerebral lesion itself. Nevertheless, five
      potential therapeutic objectives can be identified. For cerebral infarction, the
      best treatment is prevention, including targeted preventive treatments for
      specific subsets of patients or individuals with different risk factors.
      Incidence rates and mortality rates of stroke have been successfully reduced in
      certain developed countries by adoption of a public health approach to the
      prevention and control of risk factors. To rescue the still viable but injured
      nerve cells, within the ischemic penumbra, effective therapy should be begun at
      the earliest possible time. Measures to halt or reverse programmed cell death, to
      enhance the intrinsic autoprotective and repair mechanisms, are under active
      study. The existence of down-regulated brain regions, where normal nerve cells
      have far less activities to perform due to interruption of information exchange
      with the infarct area, and the possibility to reactivate them are worthy of
      attention.

PMID- 9516072
TI  - Stroke and functional rehabilitation: the Chinese experience.
AB  - According to an epidemiological study of cerebrovascular disease carried out in
      China in 1986, the prevalence, incidence, and mortality rates were
      159.93/100,000, 115.61/100,000, and 31.33/100,000, respectively. These figures
      were high compared to available epidemiological data for the rest of the world.
      This highlights the fact that, as in other countries, functional rehabilitation
      after stroke is an important medical and social need in China. Clinical
      experience shows that within a few hours to a few months after a stroke, a large
      proportion of patients spontaneously experience partial, or on occasion, complete
      recovery from neurologic symptoms. However, functional rehabilitation in medical
      care units is required because it assists in and accelerates the recovery of
      impaired function. Almitrine-raubasine has been used to improve functional
      rehabilitation after stroke for some time in China. By enriching the oxygen
      content of arterial blood, it brings more oxygen to the cerebral tissues and
      therefore promotes cerebral aerobic metabolism during ischemia. In the acute
      phase of stroke, positron emission tomography showed, in man, that almitrine
      raubasine helps normalize the ischemic penumbra area, as shown by an improvement
      in the coupling between oxygenation and perfusion. Long after stroke, single
      photon emission computed tomography showed that almitrine-raubasine restores
      normal cerebral vasodilator response to acetazolamide. With a view to further
      documenting the clinical efficacy of almitrine-raubasine on the convalescent
      period of patients with cerebrovascular disease, a double-blind, placebo
      controlled study is planned. One hundred patients with ischemic cerebrovascular
      disease in the territory of the carotid artery will be included 4-6 weeks after
      the acute onset. Two tablets daily of almitrine-raubasine or placebo will be
      prescribed for 3-6 months. Before treatment, there will be a 2-week washout
      period for all other drugs, except for antihypertensive and antidiabetic drugs.
      In addition to complete clinical monthly examinations, neurological functional
      deficit scores, Barthel index, Hasagawa Dementia scales, and CT scan are
      scheduled. The study results should confirm those reported in the scientific
      literature: although untreated patients may show spontaneous improvement,
      almitrine-raubasine should accelerate patients' functional rehabilitation.

PMID- 9516073
TI  - Pharmacological features of an almitrine-raubasine combination. Activity at
      cerebral levels.
AB  - Treatment with the combination of almitrine-raubasine increases both arterial
      oxygen partial pressure and haemoglobin oxygen saturation, reflecting an actual
      increase in the oxygen content of arterial blood. Furthermore, at the trans
      cerebral carotid artery/internal jugular vein level, the treatment increases
      cerebral arterio-venous oxygen and glucose differences, suggesting an actual
      increase both in oxygen and glucose availability and uptake in cerebral tissues.
      The increased glucose transfer to the brain is supported also by enhancement of
      the 3H-deoxyglucose uptake induced by drug pre-treatment both in normoxia and
      hypoxia. Both almitrine and raubasine act at cerebral mitochondrial levels by
      decreasing the 'loss' of the 'biological' free energy for phosphorylation
      supported by the age-related drop in the cerebral enzyme activities, such as
      phosphofructokinase, pyruvate dehydrogenase and citrate synthase. Furthermore,
      the components interfere with the alterations induced by peroxidative stress
      acting at the level of cytochrome c, cytochrome c oxidase and succinate
      dehydrogenase. Treatment with the combination almitrine-raubasine increases the
      concentration of noradrenaline metabolites, while alteration of the dopaminergic
      system is less important. The interference with the noradrenergic system is
      possibly linked to the electroencephalographic changes induced by drug treatment:
      increasing alpha-rhythm distribution and reactivity, and increases in beta-rhythm
      amplitude. Pharmacological effects of almitrine-raubasine, obtained in
      experimental conditions, correlate with clinical therapeutic efficacy, e.g., in
      the treatment of cognitive disorders associated with ageing and other cerebral
      and neurosensory impairments. It is difficult to summarise, in a few pages, the
      large number of papers related to the cerebral pharmacometabolic and
      pharmacodynamic activities of the almitrine-raubasine combination. Thus, this
      review presents in sequential steps some of the interrelated research in humans
      and laboratory animals which describes in a critical way preclinical to clinical
      results.

PMID- 9516074
TI  - Clinical efficacy of almitrine-raubasine. An overview.
AB  - Different pharmacological properties of almitrine-raubasine show that this
      combination may be a good therapy for the treatment of age-related cerebral
      disorders and functional rehabilitation after stroke. Many clinical studies have
      been carried out in France and in the rest of Europe, confirming the value of
      this compound in such situations. Without discussing the complexity of clinical
      trials in both the areas of cognitive disorders and stroke, we shall present two
      studies demonstrating the beneficial effects of almitrine-raubasine against
      cognitive impairments. The first is a double-blind controlled study versus
      placebo with a 3-month follow-up period involving patients (aged between 60 and
      85) with memory loss, lack of concentration, impaired mental altertness, and
      emotional instability. The second is a controlled multicenter study of 155
      outpatients (age 70-85) presenting with cognitive decline (assessed by MMSE,
      SCAG). In both these studies, almitrine-raubasine significantly improved
      symptomatology and was superior to placebo, especially in the vascular cases.
      This confirms the validity of previous studies and justifies the indication of
      these compounds in the treatment of age-related cognitive disorders. Other
      studies also demonstrated the beneficial effect of this compound on neurosensory
      vascular disorders, with specific studies carried out on chorioretinal
      dysfunctions (visual symptomatology) and in vestibular disorders (vertigo
      associated with electronystagmographic modifications). The appropriate and usual
      dosage (2 tablets per day) and the good tolerance of the compound have been
      confirmed in a French multicentric study in 5,361 outpatients.

PMID- 9516075
TI  - The insulin-like growth factors and breast cancer--revisited.
AB  - In 1992, a special issue of Breast Cancer Research and Treatment was devoted to
      the insulin-like growth factors and breast cancer. In that issue, identification
      of the key components of the IGF system was reviewed and their potential role in
      breast cancer growth was described. In this issue, we revisit the IGF system with
      particular attention to data that further supports their role in the growth
      regulation of breast cancer. Several new facets of the IGF system are described,
      and several laboratories have more clearly defined how each individual component
      of the IGF system may influence breast cancer biology.

PMID- 9516076
TI  - Role of IGF-I in normal mammary development.
AB  - Growth hormone (GH) is now believed to be the pituitary factor that is
      responsible for mammary ductal morphogenesis. Mammary development at puberty
      occurs because of synergy between GH and estrogen on formation of terminal end
      buds (TEBs). TEBs extend into the substance of the mammary gland fat pad,
      resulting in ductal morphogenesis. Ultimately, the whole mammary fat pad
      accommodates a complex network of ducts. IGF-I or des(1-3) IGF-I mimic the
      actions of GH on TEB formation in hypophysectomized, gonadectomized rats. Since
      GH stimulates IGF-I mRNA within the mammary gland synergistically, we hypothesize
      that IGF-I partially mediates actions of GH in mammary gland development. Studies
      in transgenic mice overexpressing IGF-I, des(1-3) IGF-I, or IGFBP-3 show that IGF
      I causes ductal hypertrophy in the lactating mouse and prevention of post
      lactational mammary gland involution. One of the mechanisms for this effect
      involves apoptosis. The potential role of GH or IGF-I in mammary carcinogenesis,
      and the applicability of animal studies to humans, are discussed.

PMID- 9516077
TI  - Endocrine effects of IGF-I on normal and transformed breast epithelial cells:
      potential relevance to strategies for breast cancer treatment and prevention.
AB  - Insulin-like growth factors (IGFs) are mitogenic and anti-apoptotic peptides that
      influence the proliferative behavior of many cell types, including normal and
      transformed breast epithelial cells. IGF-I has properties of both a tissue growth
      factor and a systemic hormone: there is evidence that IGF bioactivity in tissues
      is influenced not only by local factors such as tissue expression of IGFs, IGF
      binding proteins (IGFBPs), and IGFBP proteases, but also by factors that regulate
      whole-body IGF physiology and circulating IGF-I levels. Experimental evidence
      that interventions that reduce circulating IGF-I levels reduce proliferation of
      breast neoplasms has raised interest in the possibility of developing novel
      endocrine therapies that target the growth hormone/IGF-I axis. Furthermore,
      influences of the growth hormone/IGF-I axis on normal breast epithelial cells may
      underlie recent epidemiological observations that suggest that premenopausal
      women with high circulating IGF-I level are at increased risk for breast cancer.
      These studies suggest that the growth hormone/IGF-I axis deserves investigation
      as a possible target for novel breast cancer prevention strategies.

PMID- 9516078
TI  - Paracrine/autocrine regulation of breast cancer by the insulin-like growth
      factors.
AB  - Local environmental signals regulate the growth and development of both normal
      and malignant breast epithelium. Members of the insulin-like growth factor (IGF)
      family likely influence both of these processes. The localization of IGF2 to
      stroma specifically surrounding malignant breast epithelium indicates that this
      growth factor may play a critical role in the genesis or maintenance of this
      transformed phenotype. Recent studies have sought to understand the mechanism by
      which IGF2 expressing fibroblasts are localized to the periphery of malignant
      breast cancer cells. In addition, the consequences of the expression of IGF
      signaling components likely expand beyond their direct effects on mitogenesis.
      Indirect effects predominantly associated with the IGF2 receptor could also
      influence the invasive potential of breast tumor cells.

PMID- 9516079
TI  - Structure and function of the insulin-like growth factor I receptor.
AB  - Insulin-like growth factors I and II (IGF-I, IGF-II) were originally identified
      as potent mitogens and as the mediators of growth hormone action. Besides being
      mitogenic, however, these polypeptide growth factors play a crucial role in cell
      survival, and contribute to transformation and to maintenance of the malignant
      phenotype. Here we will discuss signaling by the IGFs, focusing specifically on
      the structure and function of the IGF-I receptor and the domains of this receptor
      responsible for distinct IGF functions: mitogenesis, transformation, and
      protection from apoptosis. We will also compare the structural domains of the
      related but functionally distinct receptor for insulin.

PMID- 9516080
TI  - Type I insulin-like growth factor receptor function in breast cancer.
AB  - Experimental evidence suggests an important role of the type I IGF receptor (IGF
      IR) in breast cancer development. Breast tumors and breast cancer cell lines
      express the IGF-IR. IGF-IR levels are higher in cancer cells than in normal
      breast tissue or in benign mammary tumors. The ligands of the IGF-IR are potent
      mitogens promoting monolayer and anchorage-independent growth of breast cancer
      cells. Interference with IGF-IR activation, expression, or signaling inhibits
      growth and induces apoptosis in breast cancer cells. In addition, recent studies
      established the involvement of the IGF-IR in the regulation of breast cancer cell
      motility and adhesion. We have demonstrated that in MCF-7 cells, overexpression
      of the IGF-IR promotes E-cadherin-dependent cell aggregation, which is associated
      with enhanced cell proliferation and prolonged survival in three-dimensional
      culture. The expression or function of the IGF-IR in breast cancer cells is
      modulated by different humoral factors, such as estrogen, progesterone, IGF-II,
      and interleukin-1. The IGF-IR and the estrogen receptor (ER) are usually co
      expressed and the two signaling systems are engaged in a complex functional cross
      talk controlling cell proliferation. Despite the convincing experimental
      evidence, the role of the IGF-IR in breast cancer etiology, especially in
      metastatic progression, is still not clear. The view emerging from cellular and
      animal studies is that abnormally high levels of IGF-IRs may contribute to the
      increase of tumor mass and/or aid tumor recurrence, by promoting proliferation,
      cell survival, and cell-cell interactions. However, in breast cancer, except for
      the well established correlation with ER status, the associations of the IGF-IR
      with other prognostic parameters are still insufficiently documented.

PMID- 9516081
TI  - The mannose 6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2R), a
      putative breast tumor suppressor gene.
AB  - Loss of heterozygosity (LOH) at the mannose 6-phosphate/insulin-like growth
      factor 2 receptor gene locus (M6P/IGF2R) on 6q26-27 has recently been
      demonstrated in approximately 30% of both invasive and in situ breast cancers.
      LOH was coupled with somatic point mutations in the remaining allele in several
      instances, leading to the proposition that M6P/IGF2R is a tumor suppressor gene.
      Somatic mutations in M6P/IGF2R have also been described in hepatoma and
      gastrointestinal cancers with the replication error positive (RER+) phenotype.
      These data indicate that M6P/IGF2R loss of function mutations may be involved in
      the pathogenesis of a wide spectrum of malignancies. Extensive data on the normal
      function of the M6P/IGF2R suggest that loss of M6P/IGF2R activity may contribute
      to multiple aspects of tumor pathophysiology, including deregulated growth,
      apoptosis, angiogenesis and invasion.

PMID- 9516082
TI  - IGF-independent regulation of breast cancer growth by IGF binding proteins.
AB  - The human IGFBP family consists of at least seven proteins, designated as IGFBP
      1, -2, -3, -4, -5, -6, and-7. IGFBPs 1-6 bind IGF-I and IGF-II with high affinity
      whereas IGFBP-7, a newly identified IGFBP, binds IGFs with lower affinity and
      constitutes a low-affinity member of the IGFBP family. IGFBPs serve to transport
      the IGFs, prolong their half-lives, and modulate their biological action. At the
      cellular level, IGFBPs can either potentiate or inhibit the mitogenic effects of
      IGFs, depending upon cell types and IGFBP species (IGF-dependent action of
      IGFBPs). However, recent studies have indicated that IGFBPs, especially IGFBP-3,
      potently inhibit breast cancer cell growth in an IGF-independent manner. The IGF
      independent action of IGFBP-3 requires interaction with cell-surface association
      proteins, presumably putative IGFBP-3 specific receptors, and is responsible for
      growth inhibitory action of the known growth suppressing factors such as TGF
      beta, retinoic acid, and antiestrogens in breast cancer cells. Thus, IGFBP-3
      appears to be a major factor in a negative control system involved in regulating
      human breast cancer cell growth in vitro. IGFBP-7, representing a low affinity
      IGFBP, appears to function as an IGF-independent cell growth regulator in breast
      cancer cells. Overall structural similarity between IGFBP-7 and classical high
      affinity IGFBPs 1-6 suggests that the mechanisms of action and signaling pathways
      used by IGFBP-7 may provide insight into the IGF-independent actions of the high
      affinity IGFBPs. A fuller understanding of the IGF-independent action of IGFBPs
      will allow us to understand how the growth of neoplastic cells can be modulated
      by the IGF/IGFBP system, and how other growth factors or pharmacological agents
      can interface with this system.

PMID- 9516083
TI  - IGF system components as prognostic markers in breast cancer.
AB  - The insulin-like growth factor (IGF) family of ligands, receptors, and binding
      proteins can regulate breast cancer cell proliferation in vitro, and interruption
      of these pathways inhibits IGF-mediated cell proliferation. If the IGF family
      members are key regulators of breast cancer growth and progression in vivo, we
      would expect their expression to be an indicator of the prognosis of the disease.
      Thus, measurement of IGF expression may provide an indicator of the growth effect
      within a tumor, and provide new targets for treatment of the disease. In this
      review we will summarize the data generated thus far indicating that IGF family
      members are indicators of prognosis of breast cancer, and that measurement of the
      whole IGF family in concert may provide useful information for treatment
      strategies of breast cancer.

PMID- 9516084
TI  - Molecular genetic pathways to Wilms tumor.
AB  - Wilms tumor remains a fascinating model for understanding how genes important in
      normal human embryogenesis can also contribute, in their mutant form, to cancer
      development in childhood. The cloning of the first Wilms tumor gene, WT1, in
      1989, laid the framework for a model but also emphasized the underlying genetic
      complexity of this embryonal kidney cancer. Despite longstanding evidence for
      additional Wilms tumor gene loci, by 1997 very few of these have been cloned and
      none has yet been proven to be involved in Wilms tumorigenesis in man. However,
      the potential biological properties of these candidate genes suggest that
      disregulation of fetal mitogens, such as insulin-like growth factor 2, may be
      pivotal. Nephrogenesis is clearly sufficiently flexible to absorb many genetic
      errors. At present, it is unclear how often a simple two mutation model may
      account for Wilms tumor. Understanding how the various Wilms tumor genes
      interrelate, if indeed they do, awaits their identification. Piecing together
      these pathways may eventually lead to logical targets for therapeutic
      interventions.

PMID- 9516085
TI  - Regulation of estrogen receptor alpha function in breast cancer.
AB  - Estrogen receptor alpha (ER) plays a key role in the development and progression
      of breast cancer as well as the treatment and outcome of breast cancer patients.
      In normal mammary epithelial cells, the level of ER fluctuates during the
      menstrual cycle in response to cyclical changes in estrogen. However, in breast
      cancer normal control of ER gene expression and/or function is lost. Of
      particular interest, the absence of ER in mammary carcinomas is associated with a
      less-differentiated phenotype and resistance to endocrine therapies. This review
      focuses on our current understanding of the mechanisms that regulate ER alpha
      gene expression and function in breast cancer. These include alteration of the ER
      gene, loss of gene expression, alternative splicing of ER RNA, posttranslational
      modification of the protein, and interaction of ER with other proteins that can
      modify its function.

PMID- 9516086
TI  - Dietary flavonoid and cancer prevention: evidence and potential mechanism.
AB  - Dietary flavonoids represent a family of polyphenol compounds found in common
      food items derived from plants. Depending on structural features, flavonoids can
      be further subdivided into flavones, flavonols, isoflavones, flavanes, and
      flavanols. The biological activities of flavonoids are structure dependent and
      epidemiological studies support their role in human cancer prevention. Several
      flavonoids inhibit cancer development in animal models of chemical and UV
      carcinogenesis. However, at high dose some flavonoids themselves may also
      increase cancer incidence. Although flavonoids have been shown to inhibit cancer
      cell growth in vitro, the ability of flavonoids to limit cancer progression is
      limited in animal studies. A potential application is the possible
      synergisticaction of flavonoids with chemotherapy agents. Molecularly, flavonoids
      have antioxidant properties and can further enhance the antioxidant protein
      activities in cells and in animals. Isoflavones and some other flavonoids have
      weak affinity for the estrogen receptor. Neonatal exposure of animals to
      isoflavonoids affects the development of reproductive organs, an observation that
      opens the possibility of using isoflavonoids in the prevention of cancers of the
      reproductive system. Some growth-inhibiting flavonoids also bind to the low
      affinity type II estrogen binding sites, but the biochemical identity of type II
      sites is unknown.

PMID- 9516087
TI  - The insulin-like growth factor-I receptor signaling pathways are important for
      tumorigenesis and inhibition of apoptosis.
AB  - The biological actions of the insulin-like growth factors IGF-I and IGF-II are
      mediated by their activation of the IGF-IR, a transmembrane tyrosine kinase
      linked to the ras-raf-MAPK cascade. Functional IGF-IRs are required for the cell
      to progress through the cell cycle. Most importantly, cells lacking this receptor
      cannot be transformed by any of a number of dominant oncogenes, a finding that
      proves that the presence of the IGF-IR is important for the development of a
      malignant phenotype. Consistent with this role, the IGF-IR displays a potent
      antiapoptotic effect, both in vitro and in vivo. Because of its key role in the
      transformation process, the IGF-IR is actively studied as a potential therapeutic
      target in different types of neoplastic growth.

PMID- 9516088
TI  - Antisense oligonucleotide therapeutics for human leukemia.
AB  - The development of reliable gene disruption strategies, and their application in
      living cells, has proven to be an extraordinarily important advance for cell and
      molecular biologists. Using the various available approaches, the specific
      functions of any given gene may now be investigated directly in the relevant cell
      type. Application of similar experimental tools in a clinical setting might prove
      to be equally valuable and could well form the basis of a monumental advance in
      the practice of clinical medicine. This seems particularly true at the present
      time since much progress has been made in understanding the molecular
      pathogenesis of many diseases, including cancer. For these reasons a tremendous
      amount of interest has been generated in the use of oligodeoxynucleotides to
      modify gene expression. However, in spite of some notable successes which are
      detailed in this review, oligonucleotides have generated controversy in regards
      to their mechanism of action, reliability, and ultimate therapeutic utility.
      Nevertheless, the potential power of the "antisense" approach remains undisputed,
      and its ultimate therapeutic utility is far reaching. Accordingly, the problems
      associated with the use of these compounds are clearly worth solving. It remains
      the hope of many laboratories that the day will soon come when these techniques
      will make an important contribution to the management of CML and other neoplastic
      disorders.

PMID- 9516089
TI  - Early treatment with dornase alfa in cystic fibrosis: what are the issues?

PMID- 9516090
TI  - Effect of smaller droplet size of dornase alfa on lung function in mild cystic
      fibrosis. Dornase Alfa Nebulizer Group.
AB  - Aerosolized recombinant human DNase (dornase alfa) reduces mucus viscoelasticity
      in vitro and improves pulmonary function in patients with cystic fibrosis (CF).
      We postulated that if dornase alfa could be delivered more peripherally to small
      airways in the lung in the form of smaller aerosol droplets in patients with
      early airway obstruction, the increase in pulmonary function from baseline might
      be improved. CF patients (n = 749) with mild lung disease (baseline forced vital
      capacity > or = 70% predicted) were randomly assigned to receive dornase alfa 2.5
      mg daily for 2 weeks by one of two nebulizer systems: 1) the Medic-Aid Durable
      SideStream nebulizer powered by the MobilAire Compressor (SS/MA) producing a
      droplet size with a mass median aerodynamic diameter (MMAD) of 2.1 microm; or 2)
      the Hudson T Up-draft nebulizer with a DeVilbiss Pulmo-Aide compressor (HT/PA)
      with an MMAD of 4.9 microm. Spirometry was performed at baseline and following 14
      days of treatment. Dornase alfa delivered by both nebulizer systems produced
      small but statistically significant improvements in pulmonary function compared
      with baseline. There was a trend (P = 0.06) toward greater improvement in forced
      expiratory flow in 1 s in the SS/MA group (4.3%) compared with the HT/PA group
      (2.5%). These results indicate that the short-term spirometric response to
      dornase alfa is influenced in part by the physical characteristics of the aerosol
      in patients with mild lung disease. We speculate that this may be true for other
      therapeutic aerosols, and it appears that localization of disease in the lung
      plays a role in the response to inhaled agents.

PMID- 9516091
TI  - Placebo-controlled, double-blind, randomized study of aerosolized tobramycin for
      early treatment of Pseudomonas aeruginosa colonization in cystic fibrosis.
AB  - In chronic Pseudomonas aeruginosa pulmonary infection of patients with cystic
      fibrosis (CF), antibiotic therapy generally fails to eradicate the bacterial
      pathogen. The mucoid bacterial phenotype, high sputum production by the host, and
      low airway levels of antibiotics seem to be responsible for the observed decrease
      in antibiotic efficacy. We hypothesized that early antibiotic treatment by
      inhalation in CF patients may be able to prevent or at least delay airway
      infection. In a prospective placebo-controlled, double-blind, randomized
      multicenter study, 22 CF patients received either 80 mg b.i.d. of aerosolized
      tobramycin or placebo for a period of 12 months shortly after the onset of P.
      aeruginosa pulmonary colonization. Two patients in the tobramycin and six
      patients in the placebo group stopped inhalation before the 12 month treatment
      period. Using life table analysis, the time to conversion from a P. aeruginosa
      positive to a P. aeruginosa-negative respiratory culture was significantly
      shorter in the tobramycin-treated group than in the placebo group (P < 0.05, log
      rank test). Lung function parameters and markers of inflammation did not change
      in either group during treatment. The results of this study suggest that early
      tobramycin inhalation may prevent and/or delay P. aeruginosa pulmonary infection
      in CF patients.

PMID- 9516092
TI  - Left ventricular perfusion deficit in patients with cystic fibrosis.
AB  - Left ventricular failure is not considered an important feature in cystic
      fibrosis (CF), but abnormalities of left ventricular function have been reported.
      Except for a few cases of heart failure in neonates with CF, there is no evidence
      of a primary disorder of the myocardium in patients with CF. Since left
      ventricular perfusion disturbances can cause left ventricular dysfunction, we
      decided to investigate left ventricular perfusion during exercise using sestamibi
      Tc-99m-labeled macroaggregates. Eighteen CF patients with varying degrees of
      disease severity participated in the study. They underwent a thorough clinical
      evaluation, lung perfusion scan, pulmonary function testing, echocardiography,
      transcutaneous measurement of oxygen saturation at rest and during exercise, and
      an exercise test with injection of sestamibi-Tc-99m-labeled macroaggregates at
      peak exercise. Six patients (33%) showed abnormalities of the myocardial
      distribution of sestamibi-Tc-99m-labeled macroaggregates during exercise.
      Scanning abnormalities correlated with the clinical score, mean maximum
      expiratory flow at 50% of vital capacity (MEF50), and arterial oxygen
      desaturation during exercise. We conclude that deficits in left ventricular
      uptake of sestamibi-Tc-99m-labeled macroaggregates during exercise seem common in
      patients with severe CF lung disease. The cause of these deficits is not fully
      understood, but the occurrence seems to be associated with a poor prognosis.

PMID- 9516093
TI  - Nasal airway dimensions and lung function in awake, healthy neonates.
AB  - Possible relations between nasal airway dimensions and measures of lung function
      are not well established. It has been suggested that a major part of airway
      resistance is found in the nose. However, little is known about the shape of
      tidal flow volume (TFV) loops in relation to nasal caliber. We therefore
      investigated whether lung function assessed by tidal breathing in healthy newborn
      infants was affected by nasal airway dimensions. Nasal airway dimensions were
      measured in 17 healthy newborn babies (mean age, 2.7 days) by acoustic rhinometry
      before and immediately after lung function measurements. Lung function was
      evaluated by TFV loops and passive respiratory mechanics (single-breath occlusion
      technique), first with both nostrils open, and subsequently immediately after
      occlusion of the larger of the two nostrils, causing at least a 50% reduction in
      nasal minimum cross-sectional area (MCA). Neither the TFV expiratory ratios (time
      and volume to reach peak flow to total time and volume, respectively
      [t(PTEF)/t(E) and V(PTEF)/V(E), respectively]), nor resistance or compliance of
      the total respiratory system differed significantly regardless of whether one or
      both nostrils were open. With one nostril closed there were no significant
      effects on any of the measured lung function parameters. We conclude that in
      healthy awake neonates reducing the cross-sectional area of nasal dimensions by
      50% does not affect TFV loops or passive respiratory mechanics.

PMID- 9516094
TI  - Meconium aspiration induces a concentration-dependent pulmonary hypertensive
      response in newborn piglets.
AB  - To investigate the effects of aspirating different meconium concentrations on the
      pulmonary circulation in 10- to 12-day-old piglets, 30 catheterized animals were
      studied. The piglets received an intratracheal bolus of 3 ml/kg of a mixture of
      human meconium in saline with concentrations of 20 mg/ml (light, n = 7), 40 mg/ml
      (moderate, n = 6), or 65 mg/ml (thick, n = 10) meconium in saline. Control
      piglets (n = 7) received 3 ml/kg of intratracheal saline. Pulmonary and systemic
      pressures were measured and vascular resistances calculated at baseline and
      serially for 4 hours after instillation. Four of the piglets died early and were
      excluded from the study. In addition, 23 samples of human meconium-stained
      amniotic fluid were collected at delivery for determination of their meconium
      concentration. After an initial rise in pulmonary artery pressure and vascular
      resistance after meconium and saline instillation, pulmonary artery pressure and
      resistance increased progressively and concentration-dependently in the meconium
      groups, but returned to baseline in the control group. The saline and meconium
      induced initial increases, and the subsequent meconium-stimulated progressive
      rise in vascular resistance occurred mainly in the postarterial segment. There
      were no significant changes in systemic hemodynamics. Mean airway pressure
      increased and oxygenation deteriorated after meconium instillation. The
      impairment of oxygenation depended on the meconium concentration in the instilled
      bolus and persisted throughout the study after moderate and thick meconium
      instillation. Similarly, the intrapulmonary shunt fraction increased initially
      and remained elevated in the moderate and thick meconium groups. Meconium
      concentrations in the human amniotic fluid samples were in the same range as
      concentrations used in the present experimental study. These results indicate
      that aspirated meconium at concentrations found in light to moderate meconium
      stained human amniotic fluid has significant effects on pulmonary hemodynamic and
      oxygenation in newborn piglets.

PMID- 9516095
TI  - Effects of inhaled fluticasone propionate administered with metered dose inhaler
      and spacer in mild to moderate croup: a negative preliminary report.
AB  - Beneficial effects of treatment of viral croup with inhaled corticosteroids and
      administered with a jet-nebulizer have been reported in recent years. To
      facilitate such therapy at home and avoid hospitalization, the administration of
      inhaled corticosteroids with a metered dose inhaler (MDI) with a holding-chamber
      was studied as a potential alternative. In a hospital-based prospective, double
      blind, randomized study, 17 children admitted with croup were treated with either
      fluticasone propionate MDI (2,000 microg with the Babyhaler spacer) or placebo.
      The primary outcome variable was the croup symptom score recorded from 0 up to 24
      hours. Secondary outcome variables were the need for administration of nebulized
      corticosteroids with a nebulizer, the need for intubation, and the duration of
      hospitalization. The administration of the drug with an MDI and spacer was well
      tolerated in each child. In all children the clinical course was favorable,
      without any significant differences between the actively treated and placebo
      treated group. One child needed additional use of inhaled corticosteroids with a
      jet nebulizer, despite treatment with fluticasone. Mean duration of
      hospitalization was 2.6 (1-4) and 2.4 (1-4) days for treatment with fluticasone
      and placebo, respectively. No undesirable side effects of treatment were
      reported. In conclusion, this study did not demonstrate therapeutic benefits of
      fluticasone propionate when administered with an MDI and a spacer compared with
      placebo. We hypothesize that the lack of effect is probably due to the inadequate
      deposition of adequate inhaled corticosteroids in the upper airways.

PMID- 9516096
TI  - Evidence-based pediatric pulmonary medicine: how can it help?
AB  - Evidence-based medicine aims to identify, critically appraise, and apply the best
      available evidence in making decisions about the care of patients. These aims are
      similar to those conscientious clinicians have always sought to achieve, but an
      evidence-based approach applies a systematic and rigorous methodology to this
      process to ensure that the evidence applied is relevant and of high quality.
      Because of the volume of potentially relevant information that needs to be
      accessed from the medical literature, many clinicians rely on reviews of the
      evidence. Systematic reviews provide summaries of the results of evidence-based
      healthcare, which can be made available to clinicians, healthcare administrators,
      and patients. The use of explicit, systematic methods in reviews limits bias
      (systematic errors) and reduces random errors (simple mistakes), thus providing
      reliable results on which to draw conclusions and make decisions. Meta-analysis
      is the use of statistical methods to summarize the results of independent
      studies. When used appropriately, meta-analysis can provide more precise
      estimates of the effects of healthcare than those derived from the individual
      studies included in a review. Childhood respiratory diseases can be a challenging
      area in which to undertake clinical research. These challenges include diagnostic
      uncertainty, lack of objective endpoints, and aspects of generalizability of
      randomized controlled trials. Despite these difficulties, there are now many
      examples of systematic reviews and evidence-based approaches in pediatric
      pulmonology. If applied appropriately, they can ensure that management of
      patients is based on clinically useful diagnostic tests and treatments that have
      been shown to be effective and not harmful.

PMID- 9516097
TI  - Improved morbidity with the use of nasal continuous positive airway pressure in I
      cell disease.
AB  - Patients with I-cell disease (mucolipidosis II) present with progressive
      morbidity failure to thrive, cardiomegaly, and recurrent respiratory tract
      infections leading to progressive deterioration and early death. We evaluated use
      of nasal continuous positive airway pressure (NCPAP) for 6 months in a 2-year-old
      girl with I-cell disease, obstructive sleep apnea (OSA), and craniofacial
      anomalies. We observed a marked decrease in hospitalizations for respiratory
      problems and a marked improvement in arterial blood gases with the use of NCPAP.
      In patients with I-cell disease, anatomical defects with superimposed upper
      respiratory tract infections cause worsening of OSA, and OSA contributes
      significantly to morbidity. In such patients NCPAP can lessen morbidity and can
      improve the quality of life.

PMID- 9516098
TI  - Resolution of severe bronchiectasis after removal of long-standing retained
      foreign body.
AB  - Saccular bronchiectasis secondary to the presence of a long retained foreign body
      is considered irreversible and an indication for resection of the diseased
      segment or lobe. We describe a 3 1/2 year-old girl with a retained organic
      foreign body for 18 months, and who was treated conservatively after laser
      resection and extraction of the inflammatory mass from the bronchus intermedius
      followed by complete resolution of the bronchiectasis. We suggest that even
      severe bronchiectasis following prolonged retention of a foreign body may be
      reversible after removal of the obstruction and reestablishment of airway
      patency.

PMID- 9516099
TI  - Demonstration of tracheal bronchus associated with tracheal stenosis using direct
      coronal computed tomography.
AB  - A 2-year-old boy presented with chronic wheezes and was refractory to medical
      treatment. A high carina with bilateral bronchial stenosis was erroneously
      diagnosed by bronchoscopic examination. Serial direct coronal computed
      tomographic scans showed a displaced right upper lobe tracheal bronchus
      associated with tracheal stenosis below the abnormal bronchus. A direct coronal
      computed tomographic scan of the tracheobronchial tree is a useful imaging
      technique for the delineation of airway configuration when the bronchoscope fails
      to pass beyond a stenotic region. A coronal computed tomographic scan may make
      invasive tracheobronchography unnecessary.

PMID- 9516100
TI  - Idiopathic subglottic stenosis in a nine-year-old boy: diagnosis and management.

PMID- 9516102
TI  - Isolation of a benzene valence isomer with one-electron phosphorus-phosphorus
      bonds 
AB  - A tetraphosphabenzene analog of the postulated anti-tricyclohexylene, a singlet
      biradical valence isomer of benzene, has been isolated. The tricyclic derivative
      features one-electron phosphorus-phosphorus bonds, which result from the pi*-pi*
      interaction between two diphosphirenyl radicals. Such one-electron bonds may play
      a wider role in phosphorus chemistry.

PMID- 9516103
TI  - Superfluidity within a small helium-4 cluster: the microscopic andronikashvili
      experiment 
AB  - The infrared spectrum of single oxygen carbon sulfide (OCS) molecules was
      measured inside large superfluid pure helium-4 droplets and nonsuperfluid pure
      helium-3 droplets, both consisting of about 10(4) atoms. In the helium-4
      droplets, sharp rotational lines were observed, whereas in helium-3 only a broad
      peak was found. This difference is interpreted as evidence that the narrow
      rotational lines, which imply free rotations, are a microscopic manifestation of
      superfluidity. Upon addition of 60 helium-4 atoms to the pure helium-3 droplets,
      the same sharp rotational lines were found; it appears that 60 is the minimum
      number needed for superfluidity.

PMID- 9516101
TI  - Optical amplification of ligand-receptor binding using liquid crystals.
AB  - Liquid crystals (LCs) were used to amplify and transduce receptor-mediated
      binding of proteins at surfaces into optical outputs. Spontaneously organized
      surfaces were designed so that protein molecules, upon binding to ligands hosted
      on these surfaces, triggered changes in the orientations of 1- to 20-micrometer
      thick films of supported LCs, thus corresponding to a reorientation of
      approximately 10(5) to 10(6) mesogens per protein. Binding-induced changes in the
      intensity of light transmitted through the LC were easily seen with the naked eye
      and could be further amplified by using surfaces designed so that protein-ligand
      recognition causes twisted nematic LCs to untwist. This approach to the detection
      of ligand-receptor binding does not require labeling of the analyte, does not
      require the use of electroanalytical apparatus, provides a spatial resolution of
      micrometers, and is sufficiently simple that it may find use in biochemical
      assays and imaging of spatially resolved chemical libraries.

PMID- 9516104
TI  - Elevation change of the southern greenland ice sheet 
AB  - Seasat and Geosat satellite altimeter measurements for the Greenland ice sheet
      (south of 72 degreesN latitude) show that surface elevations above 2000 meters
      increased at an average rate of only 1. 5 +/- 0.5 centimeters per year from 1978
      to 1988. In contrast, elevation changes varied regionally from -15 to +18
      centimeters per year, seasonally by +/-15 centimeters, and interannually by +/-8
      centimeters. The average growth rate is too small to determine if the Greenland
      ice sheet is undergoing a long-term change due to a warmer polar climate.

PMID- 9516105
TI  - Earth's background free oscillations 
AB  - Earth's free oscillations were considered to be transient phenomena occurring
      after large earthquakes. An analysis of records of the IDA (International
      Deployment of Accelerometers) gravimeter network shows that Earth is freely
      oscillating at an observable level even in seismically inactive periods. The
      observed oscillations are the fundamental spheroidal modes at frequencies between
      2 and 7 millihertz. Numerical modeling indicates that these incessant excitations
      cannot be explained by stacked effects of a large number of small earthquakes.
      The observed "background" free oscillations represent some unknown dynamic
      process of Earth.

PMID- 9516106
TI  - Formation of a magmatic-hydrothermal ore deposit: insights with LA-ICP-MS
      analysis of fluid inclusions 
AB  - The physical and chemical mechanism of ore precipitation in the Yankee Lode tin
      deposit (Mole Granite, Australia) was quantified by direct trace-element
      microanalysis of fluid inclusions. Laser ablation-inductively coupled plasma-mass
      spectrometry (LA-ICP-MS) was used to measure element concentrations in a series
      of fluid inclusions representing the fluid before, during, and after the
      deposition of cassiterite (SnO2). Tin precipitation was driven by mixing of hot
      magmatic brine with cooler meteoric water. At the same time, a separate magmatic
      vapor phase selectively transported copper and boron into the liquid mixture.

PMID- 9516107
TI  - Siliceous tablets in the larval shells of apatitic discinid brachiopods 
AB  - The marine bivalved Brachiopoda are abundant throughout the geological record and
      have apatitic (CaPO4-rich) or calcitic (CaCO3-rich) shells. Vesicles covering the
      larval valves of living apatitic-shelled discinids contain tablets of silica. The
      tablets are cemented into close-packed mosaics by spherular apatite in
      glycosaminoglycans. They are usually lost as vesicles degrade but leave imprints
      on the underlying apatitic shell. Similar imprints ornament larval surfaces of
      some of the earliest Paleozoic apatitic-shelled brachiopods and may also be
      indicators of siliceous biomineralization.

PMID- 9516108
TI  - Anomalous strain accumulation in the yucca mountain area, nevada 
AB  - Global Positioning System (GPS) surveys from 1991 to 1997 near Yucca Mountain,
      Nevada, indicate west-northwest crustal elongation at a rate of 1.7 +/- 0.3
      millimeters per year (1final sigma) over 34 kilometers, or 50 +/- 9 nanostrain
      per year. Global Positioning System and trilateration surveys from 1983 to 1997
      on a 14-kilometer baseline across the proposed repository site for high-level
      radioactive waste indicate that the crust extended by 0.7 to 0.9 +/- 0.2
      millimeter per year (50 to 64 +/- 14 nanostrain per year), depending on the
      coseismic effect of the Ms 5.4 1992 Little Skull Mountain earthquake. These
      strain rates are at least an order of magnitude higher than would be predicted
      from the Quaternary volcanic and tectonic history of the area.

PMID- 9516109
TI  - Test of general relativity and measurement of the lense-thirring effect with two
      earth satellites 
AB  - The Lense-Thirring effect, a tiny perturbation of the orbit of a particle caused
      by the spin of the attracting body, was accurately measured with the use of the
      data of two laser-ranged satellites, LAGEOS and LAGEOS II, and the Earth
      gravitational model EGM-96. The parameter &mgr;, which measures the strength of
      the Lense-Thirring effect, was found to be 1.1 +/- 0.2; general relativity
      predicts &mgr; identical with 1. This result represents an accurate test and
      measurement of one of the fundamental predictions of general relativity, that the
      spin of a body changes the geometry of the universe by generating space-time
      curvature.

PMID- 9516110
TI  - Quantitation of HIV-1-specific cytotoxic T lymphocytes and plasma load of viral
      RNA.
AB  - Although cytotoxic T lymphocytes (CTLs) are thought to be involved in the control
      of human immunodeficiency virus-type 1 (HIV-1) infection, it has not been
      possible to demonstrate a direct relation between CTL activity and plasma RNA
      viral load. Human leukocyte antigen-peptide tetrameric complexes offer a specific
      means to directly quantitate circulating CTLs ex vivo. With the use of the
      tetrameric complexes, a significant inverse correlation was observed between HIV
      specific CTL frequency and plasma RNA viral load. In contrast, no significant
      association was detected between the clearance rate of productively infected
      cells and frequency of HIV-specific CTLs. These data are consistent with a
      significant role for HIV-specific CTLs in the control of HIV infection and
      suggest a considerable cytopathic effect of the virus in vivo.

PMID- 9516111
TI  - Biodiversity assessment and conservation strategies 
AB  - The efficient representation of all species in conservation planning is
      problematic. Often, species distribution is assessed by dividing the land into a
      grid; complementary sets of grids, in which each taxon is represented at least
      once, are then sought. To determine if this approach provides useful surrogate
      information, species and higher taxon data for South African plants and animals
      were analyzed. Complementary species sets did not coincide and overlapped little
      with higher taxon sets. Survey extent and taxonomic knowledge did not affect this
      overlap. Thus, the assumptions of surrogacy, on which so much conservation
      planning is based, are not supported.

PMID- 9516113
TI  - Transcriptional and posttranscriptional plant gene silencing in response to a
      pathogen 
AB  - Plants are able to respond to pathogen attack to restrain development of a
      systemic infection. The response of Brassica napus (oilseed rape) to systemic
      infection with the DNA virus cauliflower mosaic virus was shown to result in
      enhancement and subsequent suppression of viral gene expression in parallel with
      changes in symptom expression. Transgenes with homology to viral sequences were
      also affected. This phenomenon, which was shown to be mediated by both
      transcriptional and posttranscriptional mechanisms, might be related to
      regulation of highly expressed genetic elements.

PMID- 9516112
TI  - Competition in retinogeniculate patterning driven by spontaneous activity.
AB  - When contacts are first forming in the developing nervous system, many neurons
      generate spontaneous activity that has been hypothesized to shape appropriately
      patterned connections. In Mustela putorius furo, monocular intraocular blockade
      of spontaneous retinal waves of action potentials by cholinergic agents altered
      the subsequent eye-specific lamination pattern of the lateral geniculate nucleus
      (LGN). The projection from the active retina was greatly expanded into territory
      normally belonging to the other eye, and the projection from the inactive retina
      was substantially reduced. Thus, interocular competition driven by endogenous
      retinal activity determines the pattern of eye-specific connections from retina
      to LGN, demonstrating that spontaneous activity can produce highly stereotyped
      patterns of connections before the onset of visual experience.

PMID- 9516114
TI  - Contingency and determinism in replicated adaptive radiations of island lizards 
AB  - The vagaries of history lead to the prediction that repeated instances of
      evolutionary diversification will lead to disparate outcomes even if starting
      conditions are similar. We tested this proposition by examining the evolutionary
      radiation of Anolis lizards on the four islands of the Greater Antilles.
      Morphometric analyses indicate that the same set of habitat specialists, termed
      ecomorphs, occurs on all four islands. Although these similar assemblages could
      result from a single evolutionary origin of each ecomorph, followed by dispersal
      or vicariance, phylogenetic analysis indicates that the ecomorphs originated
      independently on each island. Thus, adaptive radiation in similar environments
      can overcome historical contingencies to produce strikingly similar evolutionary
      outcomes.

PMID- 9516115
TI  - Monoallelic expression of the interleukin-2 locus.
AB  - The lymphokine interleukin-2 (IL-2) is responsible for autocrine cell cycle
      progression and regulation of immune responses. Uncontrolled secretion of IL-2
      results in adverse reactions ranging from anergy, to aberrant T cell activation,
      to autoimmunity. With the use of fluorescent in situ hybridization and single
      cell polymerase chain reaction in cells with different IL-2 alleles, IL-2
      expression in mature thymocytes and T cells was found to be tightly controlled by
      monoallelic expression. Because IL-2 is encoded at a nonimprinted autosomal
      locus, this result represents an unusual regulatory mode for controlling the
      precise expression of a single gene.

PMID- 9516117
TI  - Species distributions, land values, and efficient conservation 
AB  - Efforts at species conservation in the United States have tended to be
      opportunistic and uncoordinated. Recently, however, ecologists and economists
      have begun to develop more systematic approaches. Here, the problem of
      efficiently allocating scarce conservation resources in the selection of sites
      for biological reserves is addressed. With the use of county-level data on land
      prices and the incidence of endangered species, it is shown that accounting for
      heterogeneity in land prices results in a substantial increase in efficiency in
      terms of either the cost of achieving a fixed coverage of species or the coverage
      attained from a fixed budget.

PMID- 9516116
TI  - Structure of nitric oxide synthase oxygenase dimer with pterin and substrate.
AB  - Crystal structures of the murine cytokine-inducible nitric oxide synthase
      oxygenase dimer with active-center water molecules, the substrate L-arginine (L
      Arg), or product analog thiocitrulline reveal how dimerization, cofactor
      tetrahydrobiopterin, and L-Arg binding complete the catalytic center for
      synthesis of the essential biological signal and cytotoxin nitric oxide. Pterin
      binding refolds the central interface region, recruits new structural elements,
      creates a 30 angstrom deep active-center channel, and causes a 35 degrees helical
      tilt to expose a heme edge and the adjacent residue tryptophan-366 for likely
      reductase domain interactions and caveolin inhibition. Heme propionate
      interactions with pterin and L-Arg suggest that pterin has electronic influences
      on heme-bound oxygen. L-Arginine binds to glutamic acid-371 and stacks with heme
      in an otherwise hydrophobic pocket to aid activation of heme-bound oxygen by
      direct proton donation and thereby differentiate the two chemical steps of nitric
      oxide synthesis.

PMID- 9516118
TI  - Hydrops fetalis caused by alpha-thalassemia: an emerging health care problem.

PMID- 9516119
TI  - Regulation of allergic inflammation and eosinophil recruitment in mice lacking
      the transcription factor NFAT1: role of interleukin-4 (IL-4) and IL-5.
AB  - Transcription factors of the NFAT (nuclear factor of activated T cells) family
      regulate the expression of many genes encoding immunoregulatory cytokines and
      cell surface proteins during the immune response. The NFAT protein NFAT1 (NFATp)
      is expressed and functional in T cells, B cells, mast cells, and natural killer
      cells. Here we report a detailed analysis of the enhanced eosinophil responses of
      NFAT1-deficient mice, observed in an in vivo model of allergic inflammation. In
      addition to the pleural eosinophilia described previously, NFAT1-/- mice that
      have been sensitized with antigen display a significant increase, relative to
      wild-type mice, in the numbers of eosinophils in bone marrow and peripheral
      blood. After restimulation with antigen in vitro, antigen-responsive T cells from
      the draining lymph nodes of NFAT1-/- mice show increased expression of mRNA
      encoding the Th2 cytokines interleukin-4 (IL-4), IL-5, and IL-13. Consistent with
      this finding, there is a pronounced increase in the levels of IL-5 and IL-13 in
      the pleural cavities of sensitized NFAT1-/- mice after allergen challenge in
      vivo. Furthermore, development of eosinophilia depends on overexpression of IL-4
      and IL-5, because it is strongly inhibited by administration of neutralizing
      antibodies to either of these cytokines. These results indicate that NFAT1
      deficient mice are prone to develop a classically allergic phenotype
      characterized by eosinophilia and increased production of Th2 cytokines. Thus,
      the presence of NFAT1 might inhibit the allergic response, perhaps by interfering
      with the development of Th2 immune responses, and the lack or dysfunction of
      NFAT1 could potentially underlie certain cases of atopic disease.

PMID- 9516120
TI  - Anti-VLA4/VCAM-1-induced mobilization requires cooperative signaling through the
      kit/mkit ligand pathway.
AB  - Although a large body of data on mobilization have yielded valuable clues, the
      mechanism(s) dictating egress of stem/progenitor cells during baseline
      hematopoiesis and after their mobilization are poorly understood. We have
      previously provided functional in vivo evidence that cytoadhesion molecules,
      specifically the beta1 integrins, are involved in mobilization; however, the
      mechanism by which this was achieved was unclear. To provide further insights
      into the anti-very late antigen 4 (VLA4)/anti-vascular cell adhesion molecule 1
      (VCAM-1)-induced mobilization, we used these antibodies to treat mutant mice with
      compromised growth factor receptor function. We found that mobilization by anti
      VLA4 does not depend on a functional granulocyte colony-stimulating factor,
      interleukin-7 (IL-7), or IL-3alpha receptor. By contrast, the functional kit
      receptor is required, because W/Wv mice responded minimally, whereas Steel-Dickie
      (Sl/Sld) responded normally. Both Wv and Sl/Sld mice did not respond to anti-VCAM
      1 treatment, in contrast to their +/+ littermates and despite normal levels of
      VCAM-1 expression in bone marrow cells. The defective response to anti-VCAM-1 in
      W/Wv mice was corrected after their transplantation with +/+ cells. mev/mev mice
      showed increased numbers of circulating progenitors before treatment and a
      heightened response after anti-VLA4 or anti-VCAM-1 treatment. Downmodulation of
      kit expression was detected in normal bone marrow cells after anti-VLA4
      treatment. On the strength of the above findings we conclude that (1) anti
      VLA4/VCAM-1-induced mobilization likely requires signaling for stimulation of
      cell migration; (2) this cooperative signaling involves the kit/kit ligand
      pathway, and provides a novel example of integrin/cytokine crosstalk; and (3)
      migration mediated through the kit/kit ligand pathway may be a common contributor
      to different mobilization stimuli. Dissection of the exact molecular pathways
      that lead to mobilization remains a future challenge.

PMID- 9516121
TI  - Eotaxin induces a rapid release of eosinophils and their progenitors from the
      bone marrow.
AB  - The CC-chemokine eotaxin is a potent eosinophil chemoattractant that stimulates
      recruitment of eosinophils from the blood to sites of allergic inflammation.
      Mobilization from the bone marrow is an important early step in eosinophil
      trafficking during the allergic inflammatory response. In this paper we examine
      the potential of eotaxin to mobilize eosinophils and their progenitors from bone
      marrow. Eotaxin stimulated selective, dose-dependent chemotaxis of guinea pig
      bone marrow eosinophils in vitro. Intravenous injection of eotaxin (1 nmol/kg)
      into guinea pigs in vivo stimulated a rapid blood eosinophilia (from 3.9 +/- 1.2
      to 28 +/- 9.9 x 10(4) eosinophils/mL at 30 minutes) and a corresponding decrease
      in the number of eosinophils retained in the femoral marrow (from 9.0 +/- 0. 8 to
      4.8 +/- 0.8 x 10(6) eosinophils per femur). To show a direct release of
      eosinophils from the bone marrow an in situ perfusion system of the guinea pig
      femoral bone marrow was developed. Infusion of eotaxin into the arterial supply
      of the perfused femoral marrow stimulated a rapid and selective release of
      eosinophils into the draining vein. In addition, eotaxin stimulated the release
      of colony-forming progenitor cells. The cytokine interleukin-5 was chemokinetic
      for bone marrow eosinophils and exhibited a marked synergism with eotaxin with
      respect to mobilization of mature eosinophils from the femoral marrow. Thus,
      eotaxin may be involved in both the mobilization of eosinophils and their
      progenitors from the bone marrow into the blood and in their subsequent
      recruitment into sites of allergic inflammation.

PMID- 9516122
TI  - A20 inhibits NF-kappaB activation in endothelial cells without sensitizing to
      tumor necrosis factor-mediated apoptosis.
AB  - Expression of the NF-kappaB-dependent gene A20 in endothelial cells (EC) inhibits
      tumor necrosis factor (TNF)-mediated apoptosis in the presence of cycloheximide
      and acts upstream of IkappaBalpha degradation to block activation of NF-kappaB.
      Although inhibition of NF-kappaB by IkappaBalpha renders cells susceptible to TNF
      induced apoptosis, we show that when A20 and IkappaBalpha are coexpressed, the
      effect of A20 predominates in that EC are rescued from TNF-mediated apoptosis.
      These findings place A20 in the category of "protective" genes that are induced
      in response to inflammatory stimuli to protect EC from unfettered activation and
      from undergoing apoptosis even when NF-kappaB is blocked. From a therapeutic
      perspective, genetic engineering of EC to express an NF-kappaB inhibitor such as
      A20 offers the mean of achieving an anti-inflammatory effect without sensitizing
      the cells to TNF-mediated apoptosis.

PMID- 9516123
TI  - Erythroid Kruppel-like factor is essential for beta-globin gene expression even
      in absence of gene competition, but is not sufficient to induce the switch from
      gamma-globin to beta-globin gene expression.
AB  - Different genes in the beta-like globin locus are expressed at specific times
      during development. This is controlled, in part, by competition between the genes
      for activation by the locus control region. In mice, gene inactivation of the
      erythroid Kruppel-like factor (EKLF) transcription factor results in a lethal
      anemia due to a specific and substantial decrease in expression of the
      fetal/adult-stage-specific beta-globin gene. In transgenic mice carrying the
      complete human beta-globin locus, EKLF ablation not only impairs human beta
      globin-gene expression but also results in increased expression of the human
      gamma-globin genes during the fetal/adult stages. Hence, it may appear that EKLF
      is a determining factor for the developmental switch from gamma-globin to beta
      globin transcription. However, we show here that the function of EKLF for beta
      globin-gene expression is necessary even in absence of gene competition.
      Moreover, EKLF is not developmental specific and is present and functional before
      the switch from gamma-globin to beta-globin-gene expression occurs. Thus, EKLF is
      not the primary factor that controls the switch. We suggest that autonomous
      repression of gamma-globin transcription that occurs during late fetal
      development is likely to be the initiating event that induces the switch.

PMID- 9516124
TI  - JAK2 and JAK1 constitutively associate with an interleukin-5 (IL-5) receptor
      alpha and betac subunit, respectively, and are activated upon IL-5 stimulation.
AB  - The human interleukin-5 receptor (hIL-5R) consists of a unique alpha subunit (hIL
      5Ralpha) and a common beta subunit (betac) that activate two Janus kinases (JAK1
      and JAK2) and a signal transducer and activator of transcription (STAT5). The
      precise stoichiometry of the hIL-5R subunits and the role of JAK kinases used in
      IL-5 signaling were investigated. We analyzed the interaction between hIL-5Ralpha
      and betac by immunoprecipitation using anti-hIL-5Ralpha and anti-betac monoclonal
      antibodies. The binding of JAK1 and JAK2 to each hIL-5R subunit was also
      evaluated in the hIL-5-responsive cell line, TF-h5Ralpha. It was observed that IL
      5 stimulation induced the recruitment of betac to hIL-5Ralpha, although in the
      absence of IL-5 the subunits remain independent. In the absence of IL-5, JAK2 and
      JAK1 were associated with hIL-5Ralpha and betac, respectively. IL-5 stimulation
      resulted in tyrosine phosphorylation of JAK2, JAK1, betac, and STAT5. Moreover,
      IL-5-induced dimerization of IL-5R subunits caused JAK2 activation and betac
      phosphorylation even in the absence of JAK1 activation. Furthermore, tyrosine
      phosphorylation of JAK1 was dependent on the activation of JAK2. Detailed study
      of the C-terminal truncated cytoplasmic domain of hIL-5Ralpha revealed that the
      cytoplasmic stretch at position 346-387, containing the proline-rich region, is
      necessary for JAK2 binding. These observations suggest that activation of hIL
      5Ralpha-associated JAK2 is indispensable for the IL-5 signaling event.

PMID- 9516125
TI  - Systemic overexpression of BCL-2 in the hematopoietic system protects transgenic
      mice from the consequences of lethal irradiation.
AB  - A new transgenic mouse has been generated in which the proto-oncogene BCL-2 is
      ubiquitously overexpressed. H2K-BCL-2 transgenic mice overexpress BCL-2 in all
      cells of the hematolymphoid system and have been used to assess the role of BCL-2
      in protecting cells of the hematolymphoid system from the consequences of
      ionizing radiation. We have expanded on previous studies that have demonstrated
      protection for specific (lymphoid) cell populations and show that systemic
      overexpression of BCL-2 can protect the hematopoietic system as a whole,
      including hematopoietic stem cells (HSC), thus increasing the radioresistance of
      the animal. The increase in radioresistance in H2K-BCL-2 transgenic mice has two
      components: an increase in the radioresistance of individual cells and, to a
      lesser extent, an increase in the size of certain critically important cell
      populations, such as HSC. Bone marrow transplantation experiments show that the
      increased radioresistance of the transgenic animals is provided by cells of the
      hematopoietic system. Protection against the consequences of irradiation is not
      limited to the increased expression levels of BCL-2 in transgenic mice; levels of
      endogenous BCL-2 are higher in lymphocyte populations that survive irradiation in
      wild-type mice. We show that ubiquitous overexpression of BCL-2 in the
      hematopoietic system can be used to increase the resistance of animals to lethal
      challenges such as irradiation.

PMID- 9516126
TI  - Natural killer and B-lymphoid potential in CD34+ cells derived from embryonic
      stem cells differentiated in the presence of vascular endothelial growth factor.
AB  - Differentiation of totipotent mouse embryonic stem (ES) cells to various
      lymphohematopoietic cells is an in vitro model of the hematopoietic cell
      development during embryogenesis. To understand this process at cellular levels,
      differentiation intermediates were investigated. ES cells generated progeny
      expressing CD34, which was significantly enhanced by vascular endothelial growth
      factor (VEGF). The isolated CD34+ cells were enriched for myeloid colony-forming
      cells but not significantly for erythroid colony-forming cells. When cultured on
      OP9 stroma cells in the presence of interleukin-2 and interleukin-7, the CD34+
      cells developed two types of B220+ CD34- lymphocytes: CD3- cytotoxic lymphocytes
      and CD19+ pre-B cells, and such lymphoid potential was highly enriched in the
      CD34+ population. Interestingly, the cytotoxic cells expressed the natural killer
      (NK) cell markers, such as NKR-P1, perforin, and granzymes, classified into two
      types, one of which showed target specificity of NK cells. Thus, ES cells have
      potential to generate NK-type cytotoxic lymphocytes in vitro in addition to
      erythro-myeloid cells and pre-B cells, and both myeloid and lymphoid cells seem
      to be derived from the CD34+ intermediate, on which VEGF may play an important
      role.

PMID- 9516127
TI  - Human T-cell leukemia virus type II directly acts on CD34+ hematopoietic
      precursors by increasing their survival potential. envelope-associated HLA class
      II molecules reverse this effect.
AB  - The role of human T-cell leukemia virus type II (HTLV-II) in human
      lymphoproliferative and hematopoietic abnormalities in which the retrovirus can
      be isolated is still elusive. Here we show that the C344 T-cell-derived
      lymphotropic HTLV-II type IIa Mo strain acts directly on CD34+ hematopoietic
      precursors by rescuing them from apoptosis induced by interleukin-3 (IL-3)
      deprivation. This effect is viral strain-specific, as it is not observed with the
      B-lymphotropic HTLV-II type IIb Gu strain, it does not require infection of the
      hematopoietic precursors, and, interestingly, it is strongly dependent on the
      infected cellular host from which the virus was derived. Indeed, growth
      adaptation of the Mo strain to the permissive B-cell line, BJAB, renders the
      virus no longer capable of mediating the antiapoptotic effect. However,
      pretreatment of the BJAB-adapted Mo strain with antibodies specific for HLA class
      II, but not class I, histocompatibility antigens restores the antiapoptotic
      potential of the virus. These results constitute the first evidence that HTLV-II
      retrovirus can directly influence the homeostasis of human progenitors, without
      infecting them, and that this crucial activity is strongly inhibited by the
      presence of host-derived envelope-associated HLA class II antigens.

PMID- 9516128
TI  - Vitronectin concentrates proteolytic activity on the cell surface and
      extracellular matrix by trapping soluble urokinase receptor-urokinase complexes.
AB  - Urokinase-type-plasminogen activator (uPA) and its receptor are localized in the
      vessel wall where they are involved in cellular activation and remodelling
      processes. Besides the cell surface glycolipid (GPI)-anchored urokinase receptor
      (uPAR), which binds uPA with high affinity, recent evidence points to the
      existence of soluble uPAR (suPAR), as well. In the present study, the origin,
      binding mechanism, and cellular effects of suPAR were examined. Under basal
      conditions human vascular smooth muscle cells (HVSMC), human umbilical vein
      endothelial cells (HUVEC), and monocytic cells released 0.1 to 2 ng/mL suPAR,
      which was increased twofold to fivefold after phorbol ester (PMA) stimulation, as
      measured by a function-dependent enzyme-linked immunosorbent assay (ELISA). suPAR
      alone did not bind to HVSMC or HUVEC, but reduced cellular uPA binding by 50% to
      70%. However, after removal of GPI-uPAR with phosphatidylinositol-specific
      phospholipase C, suPAR dose-dependently increased uPA binding by fourfold to
      fivefold. This increase in binding was completely inhibited by vitronectin (VN)
      and by a monoclonal antibody against VN, but not by other matrix proteins or
      antibodies. Thus, VN-mediated uPA binding to cells was regulated by the ratio of
      soluble to surface-associated uPAR. In a uPAR-deficient cell line (LM-TK-), suPAR
      increased uPA binding up to 10-fold, whereas the truncated receptor lacking the
      amino-terminal uPA-binding domain was ineffective. The formation of a ternary
      uPA/suPAR/VN-complex on the cell surface and the free extracellular matrix could
      be inhibited by a monoclonal antibody against VN, as well as by plasminogen
      activator inhibitor-1 (PAI-1). Moreover, VN-mediated binding of the uPA/suPAR
      complex led to a fivefold increase in plasminogen activator activity. Through
      this novel pathway, VN concentrates the uPA/suPAR-complex to cell surfaces and
      extracellular matrix sites, leading to the accumulation of plasminogen activator
      activity required for cell migration and tissue remodelling processes.

PMID- 9516129
TI  - Multivesicular bodies are an intermediate stage in the formation of platelet
      alpha-granules.
AB  - We have used ultrathin cryosectioning and immunogold cytochemistry to study the
      position of alpha-granules in the endocytic and biosynthetic pathways in
      megakaryocytes and platelets. Morphologically, we distinguished three types of
      granules; so-called multivesicular bodies type I (MVB I) with internal vesicles
      only, granules with internal vesicles and an electron dense matrix (MVB II), and
      the alpha-granules with mainly a dense content and often internal membrane
      vesicles at their periphery. The MVBs were prominent in cultured megakaryocytes
      and the megakaryoblastic cell line CHRF-288, but were less numerous in bone
      marrow megakaryocytes and platelets, whereas alpha-granules were most prominent
      in mature bone marrow megakaryocytes and in platelets. The internalization
      kinetics of bovine serum albumin-gold particles and of fibrinogen positioned the
      MVB subtypes and alpha-granules sequentially in the endocytic pathway. MVBs
      contained the secretory proteins von Willebrand factor (vWF) and beta
      thromboglobulin (beta-TG), the platelet-specific membrane protein P-selectin, and
      the lysosomal membrane protein CD63. Within the MVBs, endocytosed fibrinogen and
      endogenous beta-TG were restricted to the matrix, while vWF was predominantly
      associated with internal vesicles. CD63 was also observed in association with
      internal membrane vesicles in the alpha-granules. These observations, and the
      gradual morphologic transition from granules containing vesicles to granules
      containing predominantly dense material, suggest that MVBs represent a
      developmental stage in alpha-granule maturation.

PMID- 9516130
TI  - -245 bp of 5'-flanking region from the human platelet factor 4 gene is sufficient
      to drive megakaryocyte-specific expression in vivo.
AB  - Platelet factor 4 (PF4) serves as a lineage-specific marker of megakaryocyte
      development. We previously identified two positively acting sequences in the
      human platelet factor 4 (hPF4) gene promoter that synergized to drive high-level
      luciferase reporter gene expression in vitro. Using portions of the hPF4 5'
      flanking region linked to the lacZ reporter gene, we observed in this
      investigation that constructs with -245 bp of 5'-flanking region were more active
      than constructs with -2 kb of 5'-flanking region in vitro. We created two
      independent transgenic mouse lines with a -245-bp hPF4/lacZ construct. Cells from
      these mice were tested for beta-galactosidase (beta-gal) expression at the mRNA
      level by Northern blot and semiquantitative reverse transcription polymerase
      chain reaction (RT-PCR) and at the protein level by immunohistochemistry assay.
      Mice from one line showed beta-gal expression specifically in all megakaryocytes
      of all ploidy classes from bone marrow and in platelets. Expression level was
      comparable to that driven by the 1.1-kb rat PF4 promoter in other transgenic
      mouse lines. Those in the second line showed no beta-gal expression in
      megakaryocytes, platelets, or any of the eight organs tested. The -245-bp hPF4
      promoter is capable of driving reporter gene expression in a megakaryocyte
      specific manner in transgenic mice. The small size of this megakaryocyte-specific
      promoter is compatible with that required in some viral vectors and may provide a
      model for targeting gene expression to megakaryocytes.

PMID- 9516132
TI  - Rat neutrophils express alpha4 and beta1 integrins and bind to vascular cell
      adhesion molecule-1 (VCAM-1) and mucosal addressin cell adhesion molecule-1
      (MAdCAM-1).
AB  - The alpha4 integrins, which are constitutively expressed on all human leukocyte
      subtypes except neutrophils, interact with vascular cell adhesion molecule-1
      (VCAM-1) and mucosal addressin cell adhesion molecule (MAdCAM-1) on endothelium
      to mediate selective recruitment of leukocyte subpopulations, other than
      neutrophils, to sites of inflammation. However, here we report that a different
      paradigm of leukocyte recruitment may exist in the rat. Flow cytometric analysis
      of rat neutrophils using a panel of monoclonal antibodies which recognize rat
      alpha4 and beta1 integrins showed consistent, low levels of expression. Although
      alpha4 was expressed at lower levels on neutrophils than all other rat
      leukocytes, this level of expression was sufficient to mediate significant levels
      of alpha4- and beta1-dependent neutrophil adhesion to rat and human VCAM-1, and
      alpha4-dependent, but beta1-independent, adhesion to human MAdCAM-1. These data
      suggest that rat neutrophils, unlike other species, may use alpha4 integrins to
      traffic to sites of inflammation in vivo.

PMID- 9516131
TI  - GAS6 inhibits granulocyte adhesion to endothelial cells.
AB  - GAS6 is a ligand for the tyrosine kinase receptors Rse, Axl, and Mer, but its
      function is poorly understood. Previous studies reported that both GAS6 and Axl
      are expressed by vascular endothelial cells (EC), which play a key role in
      leukocyte extravasation into tissues during inflammation through adhesive
      interactions with these cells. The aim of this work was to evaluate the GAS6
      effect on the adhesive function of EC. Treatment of EC with GAS6 significantly
      inhibited adhesion of polymorphonuclear cells (PMN) induced by phorbol 12
      myristate 13-acetate (PMA), platelet-activating factor (PAF), thrombin,
      interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha), but not
      that induced by FMLP and IL-8. GAS6 did not affect adhesion to resting EC.
      Titration experiments showed that high concentrations of GAS6 were needed to
      inhibit PMN adhesion and that inhibition was dose-dependent at the concentration
      range of 0.1 to 1 microg/mL. One possibility was that high concentrations were
      needed to overwhelm the effect of endogenous GAS6 produced by EC. In line with
      this possibility, treatment of resting EC with soluble Axl significantly
      potentiated PMN adhesion. Analysis of localization of GAS6 by confocal microscopy
      and cytofluorimetric analysis showed that it is concentrated along the plasma
      membrane in resting EC and treatment with PAF induces depletion and/or
      redistribution of the molecule. These data suggest that GAS6 functions as a
      physiologic antiinflammatory agent produced by resting EC and depleted when
      proinflammatory stimuli turn on the proadhesive machinery of EC.

PMID- 9516133
TI  - A human alloantibody interferes with binding of factor IXa to the factor VIII
      light chain.
AB  - Inhibitory antibodies directed against factor VIII develop in a substantial
      number of patients with hemophilia A as a consequence of factor VIII replacement
      therapy. These antibodies usually recognize discrete epitopes within the A2
      and/or the C2 domains of factor VIII. Here, we have characterized the antibodies
      present in the plasma of a patient affected by severe hemophilia A. The
      antibodies reacted readily with the metabolically labeled factor VIII light chain
      and fragments thereof when analyzed by immunoprecipitation. The inhibitory
      activity could be neutralized by the complete light chain, whereas only slight
      neutralization occurred with a fragment comprising the isolated C2 domain.
      Binding of the majority of antibodies to in vitro synthesized factor VIII
      fragments was dependent on the presence of amino acid residues Gln1778-Met1823, a
      region known to contain a factor IXa binding site. Functional characterization
      showed that purified IgG from the patient's serum inhibited binding of factor IXa
      to immobilized factor VIII light chain in a dose-dependent manner. These data
      indicate that human alloantibodies may inhibit factor VIII activity by
      interfering with factor IXa-factor VIIIa complex assembly.

PMID- 9516134
TI  - A fifty percent reduction of platelet surface glycoprotein Ib does not affect
      platelet adhesion under flow conditions.
AB  - Glycoprotein (GP) Ib is an adhesion receptor on the platelet surface that binds
      to von Willebrand Factor (vWF). vWF becomes attached to collagens and other
      adhesive proteins that become exposed when the vessel wall is damaged. Several
      investigators have shown that during cardiopulmonary bypass (CPB) surgery and
      also during platelet activation in vitro by thrombin or thrombin receptor
      activating peptide (TRAP) GPIb disappears from the platelet surface. Such a
      disappearance is presumed to lead to a decreased adhesive capacity. In the
      present study, we show that a 65% decrease in platelet surface expression of
      GPIb, due to stimulation of platelets in Orgaran anticoagulated whole blood with
      15 micromol/L TRAP, had no effect on platelet adhesion to both collagen type III
      and the extracellular matrix (ECM) of human umbilical vein endothelial cells
      under flow conditions in a single-pass perfusion system. In contrast to adhesion,
      ristocetin-induced platelet agglutination was highly dependent on the presence of
      GPIb. Immunoelectron microscopic studies showed that GPIb almost immediately
      returned to the platelet surface once platelets had attached to collagen. In a
      subsequent series of experiments, we showed that when less than 50% of GPIb was
      blocked by an inhibitory monoclonal antibody against GPIb (6D1), platelet
      adhesion under flow conditions remained unaffected.

PMID- 9516135
TI  - Induction of Fas (Apo-1, CD95)-mediated apoptosis of activated lymphocytes by
      polyclonal antithymocyte globulins.
AB  - Polyclonal horse antilymphocyte and rabbit antithymocyte globulins (ATGs) are
      currently used in severe aplastic anemia and for the treatment of organ allograft
      acute rejection and graft-versus-host disease. ATG treatment induces a major
      depletion of peripheral blood lymphocytes, which contributes to its overall
      immunosuppressive effects. Several mechanisms that may account for lymphocyte
      lysis were investigated in vitro. At high concentrations (.1 to 1 mg/mL) ATGs
      activate the human classic complement pathway and induce lysis of both resting
      and phytohemagglutinin (PHA)-activated peripheral blood mononuclear cells. At
      low, submitogenic, concentration ATGs induce antibody-dependent cell cytotoxicity
      of PHA-activated cells, but not resting cells. They also trigger surface Fas (Apo
      1, CD95) expression in naive T cells and Fas-ligand gene and protein expression
      in both naive and primed T cells, resulting in Fas/Fas-L interaction-mediated
      cell death. ATG-induced apoptosis and Fas-L expression were not observed with an
      ATG preparation lacking CD2 and CD3 antibodies. Susceptibility to ATG-induced
      apoptosis was restricted to activated cells, dependent on IL-2, and prevented by
      Cyclosporin A, FK506, and rapamycin. The data suggest that low doses of ATGs
      could be clinically evaluated in treatments aiming at the selective deletion of
      in vivo activated T cells in order to avoid massive lymphocyte depletion and
      subsequent immunodeficiency.

PMID- 9516136
TI  - Expression of functional CD32 molecules on human NK cells is determined by an
      allelic polymorphism of the FcgammaRIIC gene.
AB  - Human natural killer (NK) cells were thought to express only FcgammaRIIIA (CD16),
      but recent reports have indicated that NK cells also express a second type of
      FcgammaR, ie, FcgammaRII (CD32). We have isolated, cloned, and sequenced full
      length cDNAs of FcgammaRII from NK cells derived from several normal individuals
      that may represent four different products of the FcgammaRIIC gene. One
      transcript (IIc1) is identical with the already described FcgammaRIIc form. The
      other three (IIc2-IIc4) appear to represent unique, alternatively spliced
      products of the same gene, and include a possible soluble form. Analyses of the
      full-length clones have revealed an allelic polymorphism in the first
      extracellular exon, resulting in either a functional open reading frame isoform
      or a null allele. Stable transfection experiments enabled us to determine a
      unique binding pattern of anti-CD32 monoclonal antibodies to FcgammaRIIc. Further
      analyses of NK-cell preparations revealed heterogeneity in CD32 expression,
      ranging from donors lacking CD32 expression to donors expressing high levels of
      CD32 that were capable of triggering cytotoxicity. Differences in expression were
      correlated with the presence or absence of null alleles. These data show that
      certain individuals express high levels of functional FcgammaRIIc isoforms on
      their NK cells.

PMID- 9516137
TI  - Mutation analysis of the rearranged immunoglobulin heavy chain genes of marginal
      zone cell lymphomas indicates an origin from different marginal zone B lymphocyte
      subsets.
AB  - Marginal zone cell lymphoma is a recently described entity among the non
      Hodgkin's lymphomas. It likely originates from the marginal zone B cells in the
      spleen and equivalent cells in the lymph node and extranodal tissues. Recent
      evidence indicates that marginal zone B cells are functionally heterogeneous and
      may differ with respect to the pattern of somatic hypermutation in their Ig
      variable genes. To test whether marginal zone lymphomas may originate from
      different subsets of marginal zone B cells, we performed a sequence and mutation
      analysis of the rearranged Ig heavy chain (IgH) variable genes (VH) of a series
      of 14 cases of marginal zone lymphoma, occurring in the spleen (4), the lymph
      node (4), the stomach (2), the orbit (2), the tongue (1), and the skin (1). Our
      data show that marginal zone cell lymphomas preferentially rearrange the VH4,
      VH3, and VH1 family genes, without preference for any particular VH gene. Somatic
      mutations are present in 13 cases; one case of marginal zone cell lymphoma of the
      skin showed a germline configuration of the rearranged VH gene. Mutation analysis
      shows evidence of antigen selection in three cases of marginal zone cell
      lymphoma, one of the spleen, stomach, and orbit, respectively. No evidence of
      antigen selection was present in the other cases. These data indicate that
      marginal zone cell lymphomas may arise from different subsets of marginal zone B
      cells. In addition, lymphomagenesis may not be triggered by antigen in all cases
      of marginal zone cell lymphoma.

PMID- 9516138
TI  - Chronic lymphocytic leukemic B cells but not normal B cells are rescued from
      apoptosis by contact with normal bone marrow stromal cells.
AB  - The leukemic B lymphocytes from chronic lymphocytic leukemic (CLL) patients have
      a long survival in vivo, although ex vivo they rapidly die by apoptosis. To
      further investigate the mechanism of this, we have studied the influence of bone
      marrow stromal cells from normal subjects on apoptosis of B-CLL cells and normal
      umbilical cord blood (UCB) B lymphocytes. After 48 hours of incubation in medium
      alone, leukemic and normal B cells showed, respectively, 22 +/- 3% and 31 +/- 5%
      of apoptosis. Cocultures with stromal cells reduced the percentage of leukemic
      cells undergoing apoptosis (8 +/- 2%, P < . 0005) and prevented the loss of bcl-2
      protein expression. In contrast, stromal cells slightly increased normal B-cell
      apoptosis (37 +/- 6%). Direct contact between leukemic cells and stromal cells
      was found to be essential for inhibition of leukemic cell apoptosis; indeed,
      separation of leukemic cells from stromal cells by microporous membrane increased
      spontaneous apoptosis, and comparable results were obtained with stromal cell
      conditioned medium. The difference in behavior observed between normal and
      leukemic B cells plated on stromal cells can be explained by the fact that only a
      few normal B cells adhere to stromal cells in comparison with B-CLL cells. B-CLL
      cell adhesion to stromal cells is mediated by beta1 and beta2 integrins acting
      simultaneously. Contact between B-CLL cells and bone marrow stromal cells seems
      to play a major role in the accumulation and survival of B-CLL cells in the bone
      marrow.

PMID- 9516139
TI  - c-kit is expressed in soft tissue sarcoma of neuroectodermic origin and its
      ligand prevents apoptosis of neoplastic cells.
AB  - During development, mice with mutations of stem cell factor (SCF) or its receptor
      c-kit exhibit defects in melanogenesis, as well as hematopoiesis and
      gonadogenesis. Consequently, accumulating evidence suggests that the c-kit/SCF
      system plays a crucial role in all of these processes and in tumors which derive
      from them. Especially in neuroblastoma (infant tumors of neuroectoderm crest
      derivation such as melanocytes) it would appear that an autocrine loop exists
      between c-kit and SCF, and that the functional block of the c-kit receptors with
      monoclonal antibodies (MoAbs) results in a significant decrease in cellular
      proliferation. We studied the expression and role of c-kit and SCF in cell lines
      of soft tissue sarcoma of neuroectodermic origin, such as Ewing's sarcoma (ES)
      and peripheral neuro-ectodermal tumors (PNET). Using flow cytometry with MoAb
      CD117 PE, c-kit expression was highlighted in all six of the cell lines examined.
      This receptor was specifically and functionally activated by SCF, as shown by the
      binding experiments and the intracellular phosphotyrosine and immunoprecipitation
      studies that were performed. Using reverse transcriptase polymerase chain
      reaction analysis, five of the six cellular lines expressed the mRNA of SCF. In
      the medium measured by using an enzyme- linked immunosorbent assay, low
      concentrations of SCF were found: only the TC32 cellular line produced
      significantly higher levels (32 pg) than control. In serum-free culture the
      addition of SCF reduced the percentage of apoptotic cells from 25% to 90% in five
      out of the six cellular lines. This observation was confirmed by (1) the
      functional block of c-kit with MoAb: after 7 days of culture more than 30% of the
      cells were apoptotic (range 31.5% to 100%) in five out of six cell lines and
      there was also a decrease in the percentage of cells in phase S, and (2) c-kit
      antisense oligonucleotides: in the cellular lines treated with oligonucleotides
      (in relation to the untreated lines) there was a notable reduction (P < .001)
      both in the absolute number of cells and the 3H-thymidine uptake. These results
      indicate that ES and PNET express c-kit and its ligand SCF and that SCF is
      capable of protecting the tumor cells against apoptosis. Furthermore, the reverse
      transcriptase-polymerase chain reaction performed on the biopsies revealed the
      presence of mRNA both of SCF and c-kit in practically all of the samples studied.
      Our in vitro data lead us to assume that SCF may also inhibit tumor cell
      apoptosis in vivo.

PMID- 9516140
TI  - High level engraftment of NOD/SCID mice by primitive normal and leukemic
      hematopoietic cells from patients with chronic myeloid leukemia in chronic phase.
AB  - We have previously shown that intravenously injected peripheral blood (PB) or
      bone marrow (BM) cells from newly diagnosed chronic myeloid leukemia (CML)
      patients can engraft the BM of sublethally irradiated severe combined
      immunodeficient (SCID) mice. We now report engraftment results for chronic phase
      CML cells in nonobese diabetic (NOD)/SCID recipients which show the superiority
      of this latter model. Transplantation of NOD/SCID mice with 7 to 10 x 10(7)
      patient PB or BM cells resulted in the continuing presence of human cells in the
      BM of the mice for up to 7 months, and primitive human CD34+ cells, including
      those detectable as colony-forming cells (CFC), as long-term culture-initiating
      cells, or by their coexpression of Thy-1, were found in a higher proportion of
      the NOD/SCID recipients analyzed, and at higher levels than were seen previously
      in SCID recipients. The human CFC and total human cells present in the BM of the
      NOD/SCID mice transplanted with CML cells also contained higher proportions of
      leukemic cells than were obtained in the SCID model, and NOD/SCID mice could be
      repopulated with transplants of enriched CD34+ cells from patients with CML.
      These results suggest that the NOD/SCID mouse may allow greater engraftment and
      amplification of both normal and leukemic (Ph+) cells sufficient for the
      quantitation and characterization of the normal and leukemic stem cells present
      in patients with CML. In addition, this model should make practical the
      investigation of mechanisms underlying progression of the disease and the
      development of more effective in vivo therapies.

PMID- 9516141
TI  - BCR-ABL delays apoptosis upstream of procaspase-3 activation.
AB  - The p210(bcr-abl) protein was shown to inhibit apoptosis induced by DNA damaging
      agents. Apoptotic DNA fragmentation is delayed in the bcr-abl+ K562 and KCL-22
      compared with the bcr-abl- U937 and HL-60 cell lines when treated with etoposide
      concentrations that induce similar DNA damage in the four cell lines. By the use
      of a cell-free system, we show that nuclei from untreated cells that express
      p210(bcr-abl) remain sensitive to apoptotic DNA fragmentation induced by triton
      soluble extracts from p210(bcr-abl-) cells treated with etoposide. In the four
      tested cell lines, apoptotic DNA fragmentation is associated with a decreased
      expression of procaspase-3 (CPP32/Yama/apopain) and its cleavage into a p17
      active fragment, whereas the long isoform of procaspase-2 (ICH-1L) remains
      unchanged and the poly(adenosine diphosphate-ribose)polymerase protein is
      cleaved. These events are delayed in bcr-abl+ compared with bcr-abl- cell lines.
      The role of p210(bcr-abl) in this delay is confirmed by comparing the effect of
      etoposide on the granulocyte-macrophage colony-stimulating factor (GM-CSF)
      dependent UT7 cells and the bcr-abl-transfected GM-CSF-independent UT7/9 clone.
      We conclude that the cytosolic pathway that leads to apoptotic DNA fragmentation
      in etoposide-treated leukemic cells is delayed upstream of procaspase-3-mediated
      events in bcr-abl+ cell lines.

PMID- 9516142
TI  - Evidence for the involvement of both retinoic acid receptor- and retinoic X
      receptor-dependent signaling pathways in the induction of tissue transglutaminase
      and apoptosis in the human myeloma cell line RPMI 8226.
AB  - In this study, we show that both all-trans-retinoic acid (atRA) and 9-cis
      retinoic acid (9-cis-RA) are potent inducers of tissue transglutaminase (TGase
      II), an enzyme involved in apoptosis, at the level of both enzyme activity and
      mRNA in the human myeloma cell line RPMI 8226. RPMI 8226 cells were shown to
      express mRNAs for all the retinoid receptors subtypes, ie, RARalpha, RARbeta,
      RARgamma, RXRalpha, RXRbeta, and RXRgamma. To identify which of these receptors
      are involved in regulating TGase II expression, several receptor-selective
      synthetic retinoids were used. Neither CD367, a very potent retinoid that
      selectively binds and activates receptors of the RAR family, nor CD2425, an RXR
      selective agonist, induced TGase II when used alone. However, combination of
      CD367 and CD2425 resulted in nearly full induction of the enzyme. Moreover, when
      used in combination with atRA, CD367 partially inhibited the atRA-dependent
      induction of TGase II, whereas CD2425 enhanced it. The effects of Am 580, CD417,
      and CD437, three synthetic retinoids selective for the RARs subtypes RARalpha,
      RARbeta, and RARgamma, respectively, were also investigated. None of these
      compounds was able to induce TGase II when used alone; however, the combination
      of each of them with CD2425 resulted in strong induction of the enzyme activity,
      reaching 30% to 50% of the values obtained in the presence of retinoic acid and
      suggesting functional redundancy between the RAR subtypes. Finally, treatment
      with atRA or the combination of CD367 and CD2425, but not with CD367 or CD2425
      alone, was also shown to trigger apoptosis in RPMI 8226 cells, with prominent
      accumulation of TGase II immunoreactivity in apoptotic cells. Taken together
      these data suggest that the induction of TGase II expression and apoptosis in the
      RPMI 8226 myeloma cell line required ligand-dependent activation of both the RAR
      and RXR receptors.

PMID- 9516144
TI  - Gene expression by single Reed-Sternberg cells: pathways of apoptosis and
      activation.
AB  - Although Hodgkin's disease is highly responsive to treatments that cause
      apoptosis, it remains resistant to the physiological mechanisms intended to cause
      cell death. Presumably, the Reed-Sternberg cell defies endogenous apoptosis,
      persists, accumulates, and manifests the malignant disorder seen clinically. The
      Reed-Sternberg cell expresses several members of the tumor necrosis factor
      receptor superfamily. This family of receptors is involved in both activation and
      proliferation of cells, as well as either protection from or initiation of
      apoptosis in cells expressing these surface proteins. Signals from these
      receptors affect transcription. We reasoned that the activation state and
      resistance to apoptosis of Reed-Sternberg cells might be attributable to
      dysregulation of genes controling these processes. To determine gene expression
      by Reed-Sternberg cells, we developed a method of micromanipulation, global
      reverse transcription, and the reverse transcription-polymerase chain reaction
      and applied it to 51 single Reed-Sternberg cells and their variants from six
      cases of Hodgkin's disease. This report analyzes the gene expression of bcl-xs,
      bcl-xl, bax-alpha, bax-beta, fadd, fas, fas ligand (fas L), ice, TNF-alpha, TNF
      beta, TNFR1, TNFR2, TRAF1, TRAF2, TRAF3, cIAP2, and tradd at the level of mRNA in
      the single Reed-Sternberg cells and their variants. The findings here suggest a
      molecular mechanism for the activated state and in vivo survival occurring in
      untreated Reed-Sternberg cells of Hodgkin's disease.

PMID- 9516143
TI  - Somatic hypermutation, clonal diversity, and preferential expression of the VH
      51p1/VL kv325 immunoglobulin gene combination in hepatitis C virus-associated
      immunocytomas.
AB  - A high prevalence of chronic hepatitis C virus (HCV) infection has recently been
      shown in a subset of B-cell non-Hodgkin's lymphomas, most of which belong to the
      lymphoplasmacytoid lymphoma/immunocytoma subtype and are characterized by the
      production of a monoclonal IgM cryoglobulin with rheumatoid factor activity. To
      better define the stage of differentiation of the malignant B cell and to
      investigate the role of chronic antigen stimulation in the pathogenesis of the
      HCV-associated immunocytomas, we analyzed the variable (V) region gene repertoire
      in 16 cases with this type of tumor. The lymphoma-derived V gene sequences were
      successfully determined in 8 cases; 5 of them expressed the 51p1 VH gene in
      combination with the kv325 VL gene. Moreover, a monoclonal 51p1-expressing B-cell
      population was detected in 4 of the remaining immunocytomas by an allele-specific
      Ig gene fingerprinting assay, indicating that HCV-associated immunocytomas
      represent clonal proliferations of a highly selected B-cell population. Somatic
      mutations and intraclonal diversity were observed in all of the lymphoma V genes,
      and clonally related IgM and IgG VH transcripts indicative of isotype switching
      were present in one case. These findings are consistent with an antigen-driven
      process and support a role for chronic antigen stimulation in the growth and
      clonal evolution of HCV-associated immunocytomas.

PMID- 9516145
TI  - Restoration of retinoid sensitivity by MDR1 ribozymes in retinoic acid-resistant
      myeloid leukemic cells.
AB  - Complete remission is achieved in a high proportion of patients with acute
      promyelocytic leukemia (APL) after all-trans retinoic acid (RA) treatment, but
      most patients relapse and develop RA-resistant APL. We have previously reported
      that both RA-resistant HL-60 (HL-60R) and APL cells express P-glycoprotein and
      MDR1 transcripts; and these cells differentiate to mature granulocytes after
      culture with RA and P-glycoprotein antagonist. Ribozymes have been shown to be
      able to intercept a target RNA by catalytic activity. To address the role of MDR1
      in overcoming RA-resistance in APL cells, we investigated the biologic effects of
      ribozymes against the MDR1 transcript in HL-60R cells. These ribozymes
      efficiently cleaved MDR1 mRNA at a specific site in vitro. The 196 MDR1 ribozyme
      was cloned into an expression vector, and stably transfected (HL-60R/196Rz) cells
      were obtained. Expression of MDR1 transcripts was decreased in HL-60R/196Rz cells
      compared with parental HL-60R and empty vector-transfected (HL-60R/neo) cells.
      Interestingly, RA inhibited cellular proliferation and induced differentiation of
      HL-60R/196Rz cells in a dose-dependent manner, suggesting reversal of drug
      resistance in HL-60R cells by the MDR1 ribozyme. These data are direct evidence
      that P-glycoprotein/MDR1 is responsible in part for acquired resistance to RA in
      myeloid leukemic cells. The MDR1 ribozyme may be a useful tool for investigating
      the biology of retinoid resistance and may have therapeutic potential for
      patients with RA-resistant APL.

PMID- 9516146
TI  - Idiotype immunization combined with granulocyte-macrophage colony-stimulating
      factor in myeloma patients induced type I, major histocompatibility complex
      restricted, CD8- and CD4-specific T-cell responses.
AB  - Idiotypic structures expressed on the myeloma Ig protein might be regarded as a
      tumor-specific antigen. Five patients with IgG myeloma were immunized with the
      purified serum M-component by repeated intradermal injections together with
      soluble granulocyte-macrophage colony-stimulating factor (GM-CSF). All patients
      developed an idiotype (Id)-specific T-cell immunity, defined as blood T cells
      predominantly secreting interferon-gamma (IFN-gamma) and interleukin-2 (IL-2)
      (type I cells). Id-specific DNA synthesis was induced in one patient. Delayed
      type hypersensitivity against the Id was not evoked. The specific IFN-gamma/IL-2
      T-cell response was inhibited (46% to 100%) by a major histocompatibility complex
      (MHC) class I monoclonal antibody (MoAb) in all five patients. A 5% to 37%
      inhibition by an MHC class II MoAb was seen in four patients. CD4+ as well as
      CD8+ T cells enriched by magnetic microbeads contained Id-specific cells. The T
      cells recognized peptides corresponding to the complementarity-determining
      regions 1, 2, and 3 of the heavy chain of the Id. There was a transient rise of B
      cells producing IgM anti-idiotypic antibodies in all patients. The results
      indicate that immunization of myeloma patients using the autologous M-component
      and soluble GM-CSF may evoke an Id-specific predominantly MHC class I-restricted
      type I T-cell response.

PMID- 9516147
TI  - Enhanced MDR1 gene expression in human T-cell leukemia virus-I-infected patients
      offers new prospects for therapy.
AB  - Overexpression of P-glycoprotein (P-gp), the protein product of the multidrug
      resistance gene (MDR1), confers a drug resistant phenotype on cells. This
      phenotype is reminiscent of human T-cell leukemia virus (HTLV)-transformed
      leukemic cells, for which no consistently effective chemotherapeutic regime has
      been found. The presence of an active multiple drug resistance (MDR) phenotype in
      freshly isolated peripheral blood mononuclear cells (PBMC) from HTLV-I-infected
      subjects was investigated. Significant P-gp-mediated efflux activity and enhanced
      MDR1 mRNA expression was observed in nine of 10 HTLV-infected subjects. The
      development of MDR phenotypes was found to be independent of disease type or
      status with significant MDR activities being observed in adult T-cell leukemia
      (ATL), HTLV-associated myelopathy (HAM)/tropical spastic paraparesis (TSP), and
      asymptomatic HTLV-infected individuals. P-gp-mediated drug efflux was also found
      to be restricted to CD3+ T-cell populations. Furthermore, we show the novel
      finding that the MDR1 gene promoter is transcriptionally activated by the HTLV-I
      tax protein, suggesting a molecular basis for the development of drug resistance
      in HTLV-I infections. These observations open up the possibility of new
      chemotherapeutic approaches to HTLV-associated diseases through the use of P-gp
      inhibitors.

PMID- 9516148
TI  - Mechanisms of growth control of Kaposi's sarcoma-associated herpes virus
      associated primary effusion lymphoma cells.
AB  - Primary effusion lymphoma (PEL) is a distinct clinicopathologic entity associated
      with Kaposi's sarcoma-associated herpes virus (KSHV). Several cytokines,
      including interleukin-6 (IL-6), basic fibroblast growth factor (bFGF), and
      platelet-derived growth factor (PDGF) may be important for survival of KS cells.
      However, little is known about the interaction of cytokines with KSHV-infected
      lymphocytes from PEL. Therefore, we investigated what cytokines were produced by
      KSHV-infected PEL cell lines (KS-1, BC-1, BC-2), what cytokine receptors were
      expressed by these cells, what response these cells had to selected cytokines,
      and what was the effect of IL-6 antisense phosphorothioated oligonucleotides.
      Reverse transcriptase-polymerase chain reaction (RT-PCR) and protein studies
      showed that these three cell lines produced IL-10, IL-6, and the receptors for IL
      6. The granulocyte macrophage colony-stimulating factor (GM-CSF), IL-1beta, IL-8,
      IL-12, bFGF, PDGF, and c-kit transcripts were not detected in the cell lines.
      High levels (0.7 to 5 ng/mL/10(6) cells/48 hours) of IL-6 protein were
      consistently detected in supernatants of the cell lines by enzyme-linked
      immunosorbent assay (ELISA) tests. In clonogenic assays, interferon-alpha (IFN
      alpha) and IFN-gamma suppressed the clonal growth of the PEL cells, but GM-CSF,
      IL-4, IL-6, IL-8, IL-10, and oncostatin M did not change it. We examined for
      several autocrine loops that have been suggested to occur in KS. Experiments
      using antisense oligonucleotides showed that the clonal growth of KS-1 and BC-1
      was nearly 100% inhibited by IL-6 antisense oligonucleotides (10 micromol/L), but
      not at all by either oligonucleotides (</=10 micromol/L) to IL-6 sense, IL-6
      scrambled, viral IL-6 (vIL-6) antisense, or IL-10 antisense. Furthermore, the IL
      6 antisense oligonucleotides had no effect on two B-cell lymphoma cell lines,
      which were not infected with KSHV. Addition of IL-6 antibody did not inhibit
      clonal growth of any of the cell lines. Taken together, we have defined the
      cytokines and their receptors expressed on PEL cells and have found that these
      cells synthesized IL-6 and IL-6 receptors; interruption of this pathway by IL-6
      antisense oligonucleotides specifically prevented the growth of these cells.
      These findings will offer potential new therapeutic strategies for PEL.

PMID- 9516149
TI  - Flavopiridol induces apoptosis of normal lymphoid cells, causes
      immunosuppression, and has potent antitumor activity In vivo against human
      leukemia and lymphoma xenografts.
AB  - Flavopiridol is a novel semisynthetic flavone derivative of the alkaloid
      rohitukine. Flavopiridol is known to inhibit potently the activity of multiple
      cyclin-dependent kinases. We have assessed its effects on normal and malignant
      cells in preclinical animal models of localized and disseminated human
      hematopoietic neoplasms. Flavopiridol, when administered as daily bolus
      intravenous (IV) injections, produced selective apoptosis of cells in the thymus,
      spleen, and lymph nodes, resulting in atrophy of these organs. With the exception
      of the intestinal crypts, apoptosis or tissue damage was absent in all other
      organs investigated (kidneys, liver, lungs, bone/bone marrow, muscle, and heart).
      Flavopiridol had a marked apoptotic effect documented by DNA nick-end labeling,
      or DNA agarose gels in xenografts of human hematopoietic tumors HL-60, SUDHL-4,
      and Nalm/6. After treatment with 7.5 mg/kg flavopiridol bolus IV or
      intraperitoneal on each of 5 consecutive days, 11 out of 12 advanced stage
      subcutaneous (s.c.) human HL-60 xenografts underwent complete regressions, and
      animals remained disease-free several months after one course of flavopiridol
      treatment. SUDHL-4 s.c. lymphomas treated with flavopiridol at 7.5 mg/kg bolus IV
      for 5 days underwent either major (two out of eight mice) or complete (four out
      of eight mice) regression, with two animals remaining disease-free for more than
      60 days. The overall growth delay was 73.2%. The acquired immunodeficiency
      syndrome-associated lymphoma AS283 showed no significant response when
      flavopiridol was used in advanced s.c. tumors, but when treatment was initiated
      in early stages, there was a complete regression of the early tumors, and a
      significant overall growth delay (>84%). When flavopiridol was used in severe
      combined immunodeficient mice bearing disseminated human acute lymphoblastic
      leukemia Nalm/6 cells, there was 15-day prolongation in survival (P = .0089). We
      conclude that flavopiridol greatly influences apoptosis in both normal and
      malignant hematopoietic tissues. This activity was manifested in our study as a
      potent antileukemia or antilymphoma effect in human tumor xenografts, which was
      dose and schedule dependent. These findings provide compelling evidence for the
      use of flavopiridol in human hematologic malignancies.

PMID- 9516150
TI  - Expression of the Epstein-Barr virus protein LMP1 mediates tumor regression in
      vivo.
AB  - By stimulating the expression of murine IP-10 and Mig, CXC chemokines that
      inhibit neovascularization and cause damage to established tumor vasculature,
      human B cells immortalized with Epstein-Barr virus (EBV) can promote an effective
      antitumor response in athymic mice. In the present study, we examined the
      potential role of EBV in the induction of this antitumor response. Using a panel
      of EBV+ and EBV- Burkitt lymphoma (BL) cell lines, a significant correlation was
      detected between the expression of the EBV latency gene LMP1 and the occurrence
      of spontaneous tumor regression in athymic mice. Inoculation of LMP1+ and LMP1-
      BL cells in the same subcutaneous site resulted in tumors that completely
      regressed in a manner indistinguishable from that induced by EBV-immortalized B
      cells. EBV-converted BL30 and BL41 sublines infected with B95-8 virus expressed
      LMP1, generated tumors that frequently regressed spontaneously, and promoted an
      effective antitumor response against progressively growing tumors. In contrast,
      the EBV- BL30 and BL41 cell lines and the EBV-converted BL30 and BL41 infected
      with P3HR-1 virus did not express LMP1 protein, and generated progressively
      growing tumors in nude mice. When transfected with the LMP1 gene, BL41 cells
      produced tumors that regressed spontaneously in most cases, and could induce the
      regression of tumors derived from BL41 cells transfected with vector alone.
      Tumors induced by LMP1-expressing cells expressed murine IP-10 and Mig and
      displayed histological evidence of extensive tumor tissue necrosis and vascular
      damage. We conclude that the EBV protein LMP1 is likely responsible for the
      antitumor response elicited by EBV-immortalized cells in athymic mice.

PMID- 9516151
TI  - Plasmablastic morphology--an independent prognostic factor with clinical and
      laboratory correlates: Eastern Cooperative Oncology Group (ECOG) myeloma trial
      E9486 report by the ECOG Myeloma Laboratory Group.
AB  - We studied the prognostic significance of plasmablastic (PB) multiple myeloma
      (MM) in Eastern Cooperative Oncology Group Phase III trial E9486. Two reviewers
      independently reviewed 453 cases. They agreed on 37 PB (8.2%) cases and 416 non
      PB cases, achieving an 85% concordance (P < .0001). These PB cases had
      significantly lower hemoglobin and serum albumin levels, higher calcium and beta
      2-microglobuin levels, and higher percentage BM plasma cells (PC) by
      immunofluorescence. They had higher bone marrow PC labeling indices, higher serum
      soluble interleukin-6 receptor (sIL-6R) levels, and a higher probability of ras
      mutations. Three treatment regimens were used: vincristine, bis-chloro-ethyl
      nitrosourea (BCNU) melphalan, cyclophosphamide, and prednisone (VBMCP) alone;
      VBMCP with added cyclophosphamide (HiCy); or recombinant interferon alpha 2
      (rIFNalpha2). Although the numbers are low, patients with PB had a significantly
      lower response rate versus non-PB MM when treated with VBMCP (treated, 47.1% v
      nontreated, 66.5% [P = .015]). Patients with nonresponding PB had a significantly
      higher progression rate than non-PB cases (30.6% v 11.8% [P < .0001]), especially
      with VBMCP alone (35.3% v 15.8% [P = .002]), and with added HiCy (37.5% v 9.8% [P
      < .0001]), but not with added rIFNalpha2. Event-free and overall survival of PB
      MM was shorter (median years, 1.1 v 2.7 and 1.9 v 3.7, respectively [P < .0001
      for both]). In multivariate analysis, PB classification was also highly
      prognostic. There is no survival difference between the patients who were
      classified as PB by both reviewers versus patients classified as PB by only one
      reviewer. We conclude that PB MM is a discrete entity associated with more
      aggressive disease and shortened survival. Tumor cell ras mutations and increased
      sIL-6R may contribute to a higher proliferation rate and reduced survival. There
      were significant improvements in response and progression with the addition of
      HiCy and rIFNalpha2 to VBMCP, but the numbers were small and improved survival
      could not be shown.

PMID- 9516152
TI  - Intracellular localization of interleukin-6 in eosinophils from atopic asthmatics
      and effects of interferon gamma.
AB  - Eosinophils, prominent cells in asthmatic inflammation, have been shown to
      synthesize, store, and release an array of up to 18 cytokines and growth factors,
      including interleukin-6 (IL-6). In this report, we show that IL-6
      immunofluorescence localizes to the matrix of the crystalloid granule in
      peripheral blood eosinophils from atopic asthmatics using confocal laser scanning
      microscopy (CLSM). Granule localization of IL-6 was confirmed using dot-blot
      analysis and enzyme-linked immunosorbent assay (ELISA) on subcellular fractions
      of highly purified eosinophils produced from density centrifugation across a 0%
      to 45% Nycodenz gradient. IL-6 was found to coelute with eosinophil crystalloid
      granule marker proteins, including eosinophil peroxidase (EPO), major basic
      protein (MBP), arylsulfatase B, and beta-hexosaminidase. Immunoreactivity to IL-6
      colocalized with granule-associated IL-2 and IL-5 in subfractionated eosinophils.
      We also made the novel and compelling observation that interferon gamma
      (IFNgamma), a Th1-type cytokine, stimulated an early elevation in eosinophil IL-6
      immunoreactivity. A 2.5-fold enhancement of IL-6 immunoreactivity in eosinophil
      granules was observed within 10 minutes of IFNgamma treatment (500 U/mL), as
      determined by subcellular fractionation and CLSM. These findings suggest that
      IFNgamma has short-term effects on human eosinophil function and imply that a
      physiologic role exists for Th1-type cytokine modulation of Th2-type responses in
      these cells.

PMID- 9516153
TI  - Isolation and characterization of the cDNA for mouse neutrophil collagenase:
      demonstration of shared negative regulatory pathways for neutrophil secondary
      granule protein gene expression.
AB  - A characteristic of normal neutrophil maturation is the induction of secondary
      granule protein (SGP) mRNA expression. Several leukemic human cell lines mimic
      normal morphologic neutrophil differentiation but fail to express SGPs, such as
      lactoferrin (LF) and neutrophil gelatinase (NG). In contrast, two murine cell
      lines (32D C13 and MPRO) are able to differentiate into neutrophils and induce
      expression of LF and NG. Therefore, to study the normal regulation and function
      of these genes, the corresponding murine homologs must be isolated. Using cDNA
      representational difference analysis (RDA) to compare a committed myeloid
      progenitor cell line (EPRO) with the multipotent stem cell line from which it was
      derived (EML), we isolated a fragment bearing homology to human neutrophil
      collagenase (hNC). Here, we describe the cloning and characterization of a full
      length ( approximately 2 kb) clone that exhibits nearly 65% nucleotide and 73%
      amino acid identity to hNC. Ribonuclease protection analysis (RPA) of the tissues
      and cell lines shows that mouse NC (mNC) is expressed only in cell lines
      exhibiting neutrophilic characteristics, further confirming its identity as the
      mouse homolog of hNC. Furthermore, we have demonstrated a shared negative
      regulatory pathway for this and other SGP genes. We have previously shown that
      CCAAT displacement protein (CDP/cut) binds to a specific region of the LF
      promoter, and overexpression of CDP blocks G-CSF-induced upregulation of LF gene
      expression in 32D C13 cells. We show here that in these cells, upregulation of
      both NC and NG is also blocked. CDP is thus the first identified transcription
      factor that is a candidate for mediating the shared regulation of neutrophil SGP
      protein genes.

PMID- 9516154
TI  - Granulocyte colony-stimulating factor worsens the outcome of experimental
      Klebsiella pneumoniae pneumonia through direct interaction with the bacteria.
AB  - Besides its well-established effects on granulocytopoiesis, granulocyte colony
      stimulating factor (G-CSF) has been shown to have direct effects on the
      recruitment and bactericidal ability of neutrophils, resulting in improved
      survival of experimentally infected animals. We studied the effect of G-CSF on
      the course of experimental pneumonia induced by Klebsiella pneumoniae, an
      important gram-negative bacillary pulmonary pathogen. Using a highly reproducible
      murine model, we here show the paradoxical finding that mortality from infection
      was significantly increased when animals received G-CSF before induction of
      pneumonia. Administration of G-CSF promoted replication of bacteria in the liver
      and spleen, thus indicating an impairment rather than an enhancement of
      antibacterial mechanisms. By contrast, a monoclonal antibody against Klebsiella
      K2 capsule significantly reduced bacterial multiplication in the lung, liver, and
      spleen, and abrogated the increased mortality caused by G-CSF. In vitro studies
      showed a direct effect of G-CSF on K pneumoniae resulting in increased capsular
      polysaccharide (CPS) production. When bacteria were coincubated with
      therapeutically achievable concentrations of G-CSF, phagocytic uptake and killing
      by neutrophils was impaired. Western blot analysis showed three binding sites of
      G-CSF to K pneumoniae. Binding of 125I-G-CSF to K pneumoniae was displaced by an
      excess of unlabeled G-CSF, whereas an unrelated cytokine, interleukin-1alpha, did
      not compete with G-CSF binding to the bacteria. Thus, in this model, the direct
      effect of G-CSF on a bacterial virulence factor, CPS production, outweighed any
      beneficial effect of G-CSF on recruitment and stimulation of leukocytes.

PMID- 9516155
TI  - Colony-stimulating factors signal for increased transport of vitamin C in human
      host defense cells.
AB  - Although serum concentrations of ascorbic acid seldom exceed 150 micromol/L,
      mature neutrophils and mononuclear phagocytes accumulate millimolar
      concentrations of vitamin C. Relatively little is known about the mechanisms
      regulating this process. The colony-stimulating factors (CSFs), which are central
      modulators of the production, maturation, and function of human granulocytes and
      mononuclear phagocytes, are known to stimulate increased glucose uptake in target
      cells. We show here that vitamin C uptake in neutrophils, monocytes, and a
      neutrophilic HL-60 cell line is enhanced by the CSFs. Hexose uptake studies and
      competition analyses showed that dehydroascorbic acid is taken up by these cells
      through facilitative glucose transporters. Human monocytes were found to have a
      greater capacity to take up dehydroascorbic acid than neutrophils, related to
      more facilitative glucose transporters on the monocyte cell membrane. Ascorbic
      acid was not transported by these myeloid cells, indicating that they do not
      express a sodium-ascorbate cotransporter. Granulocyte (G)- and granulocyte
      macrophage colony-stimulating factor (GM-CSF) stimulated increased uptake of
      vitamin C in human neutrophils, monocytes, and HL-60 neutrophils. In HL-60
      neutrophils, GM-CSF increased both the transport of dehydroascorbic acid and the
      intracellular accumulation of ascorbic acid. The increase in transport was
      related to a decrease in Km for transport of dehydroascorbic acid without a
      change in Vmax. Increased ascorbic acid accumulation was a secondary effect of
      increased transport. Triggering the neutrophils with the peptide fMetLeuPhe led
      to enhanced vitamin C uptake by increasing the oxidation of ascorbic acid to the
      transportable moiety dehydroascorbic acid, and this effect was increased by
      priming the cells with GM-CSF. Thus, the CSFs act at least at two distinct
      functional loci to increase cellular vitamin C uptake: conversion of ascorbic
      acid to dehydroascorbic acid by enhanced oxidation in the pericellular milieu and
      increased transport of DHA through the facilitative glucose transporters at the
      cell membrane. These results link the regulated uptake of vitamin C in human host
      defense cells to the action of CSFs.

PMID- 9516156
TI  - Analysis of signal transduction pathways in human eosinophils activated by
      chemoattractants and the T-helper 2-derived cytokines interleukin-4 and
      interleukin-5.
AB  - Activation and recruitment of eosinophils in allergic inflammation is in part
      mediated by chemoattractants and T-helper 2 (Th2)-derived cytokines. However,
      little is known concerning the signal transduction mechanisms by which this
      activation occurs. We have investigated tyrosine kinase-mediated activation of
      phosphatidylinositol 3-kinase (PI3K) and compared this with the activation of the
      p21ras-ERK signaling pathway in human eosinophils. The related cytokines
      interleukin-3 (IL-3), IL-5, and granulocyte-macrophage colony-stimulating factor
      (GM-CSF), all induced PI3K activity detected in antiphosphotyrosine
      immunoprecipitates. Furthermore, the chemoattractants platelet-activating factor
      (PAF), RANTES, and C5a were also able to induce phosphotyrosine-associated PI3K
      activity. Protein kinase B (PKB) is a downstream target of PI3K activation by
      growth factors. Induction of PKB phosphorylation in human eosinophils was
      transiently induced on activation with the cytokines IL-4 and IL-5, as well as
      the chemoattractants PAF, C5a, and RANTES showing a broad activation profile.
      Surprisingly, analysis of the activation of the mitogen-activated protein (MAP)
      kinases p44(ERK1) and p42(ERK2), showed that ERK2, but not ERK1, was transiently
      activated in human eosinophils after stimulation with IL-5 or PAF. Activation
      kinetics correlated with activation of p21ras by both cytokines and
      chemoattractants as measured by a novel assay for guanosine triphosphate (GTP)
      loading. Finally, using specific inhibitors of both the p21ras-ERK and PI3K
      signaling pathways, a role was demonstrated for PI3K, but not p21ras-ERK, in
      activation of the serum-treated zymosan (STZ)-mediated respiratory burst in IL-5
      and PAF-primed eosinophils. In summary, these data show that in human
      eosinophils, Th2-derived cytokines differentially activate both PI3K and MAP
      kinase signal transduction pathways with distinct functional consequences showing
      complex regulation of eosinophil effector functions.

PMID- 9516157
TI  - The Fcgamma receptor-mediated respiratory burst of rolling neutrophils to
      cytokine-activated, immune complex-bearing endothelial cells depends on L
      selectin but not on E-selectin.
AB  - Intracellular H2O2 generation, as a measure of the respiratory burst, was
      determined after stimulation of neutrophils by immune complex (IC)-bearing human
      umbilical vein endothelial cells. Under static conditions, neutrophils basically
      responded to the immune deposits on resting endothelial cells. The rotating shear
      forces of approximately 0.7 dynes/cm2, corresponding to the physiological flow in
      postcapillary venules, completely abolished this basal H2O2 generation. After
      activation of the IC-bearing endothelial layers with interleukin-1 (IL-1) or
      tumor necrosis factor (TNF), or both, for 4 hours, rolling adhesion of the
      neutrophils was induced, accompanied by considerable H2O2 production. The
      neutrophil respiratory burst was prominently inhibited by anti-FcgammaRIII MoAb
      3G8 (72.4%), and partially by MoAb 2E1 against FcgammaRII (38.5%). Both MoAbs
      together inhibited the Fc-mediated H2O2 generation by 93. 4%. The respiratory
      burst and rolling adhesion were markedly blocked by MoAb LAM1-3 against L
      selectin (91.3%), whereas the nonfunctional anti-L-selectin MoAb LAM1-14 was
      ineffective. F(ab)2' fragments of MoAb 7A9 against E-selectin inhibited
      neutrophil rolling by 98.6%, but not the respiratory burst. Moreover, rolling
      adhesion of neutrophils and the related oxidative burst were CD11b/CD18-
      independent. In summary, L-selectin has a unique auxiliary function in triggering
      the FcgammaR-mediated respiratory burst of rolling neutrophils to IC-bearing
      endothelial cells, thereby substituting CD11b/CD18 under conditions of flow.

PMID- 9516159
TI  - Decay-accelerating factor (CD55) and membrane inhibitor of reactive lysis (CD59)
      are released within exosomes during In vitro maturation of reticulocytes.
AB  - Exosomes are membrane vesicles released by reticulocytes during their maturation
      into erythrocytes. They have a clearing function because of their enrichment with
      some proteins known to decrease or disappear from the cell surface during
      maturation, eg, acetylcholinesterase (AChE) and transferrin receptor (TfR),
      respectively. To better understand the molecular events leading to protein
      sorting in exosomes, we analyzed the expression of glycosylphosphatidylinositol
      (GPI)-anchored proteins on the exosome surface through a technique involving bead
      coupling and flow cytometry immunodetection. The presence of AChE, decay
      accelerating factor (DAF), membrane inhibitor of reactive lysis (MIRL), and
      lymphocyte function-associated antigen 3 (LFA-3) on the surface of exosomes
      obtained from normal and paroxysmal nocturnal hemoglobinuria (PNH) reticulocytes,
      suggests that (1) the GPI anchor is efficiently sorted during exosome formation,
      (2) exosome release could account for the observed discrepancy in GPI-protein
      expression between reticulocytes and erythrocytes from PNH patients, and (3)
      exosomes could have another physiologic function related to controlling membrane
      attack complex formation.

PMID- 9516158
TI  - Response of monocyte iron regulatory protein activity to inflammation: abnormal
      behavior in genetic hemochromatosis.
AB  - In genetic hemochromatosis (GH), iron overload affects mainly parenchymal cells,
      whereas little iron is found in reticuloendothelial (RE) cells. We previously
      found that RE cells from GH patients had an inappropriately high activity of iron
      regulatory protein (IRP), the key regulator of intracellular iron homeostasis.
      Elevated IRP should reflect a reduction of the iron pool, possibly because of a
      failure to retain iron. A defect in iron handling by RE cells that results in a
      lack of feedback regulation of intestinal absorption might be the basic
      abnormality in GH. To further investigate the capacity of iron retention in RE
      cells of GH patients, we used inflammation as a model system as it is
      characterized by a block of iron release from macrophages. We analyzed the iron
      status of RE cells by assaying IRP activity and ferritin content after 4, 8, and
      24 hours of incubation with lipopolysaccharide (LPS) and interferon-gamma (IFN
      gamma). RNA-bandshift assays showed that in monocytes and macrophages from 16
      control subjects, IRP activity was transiently elevated 4 hours after treatment
      with LPS and IFN-gamma but remarkably downregulated thereafter. Treatment with NO
      donors produced the same effects whereas an inducible Nitric Oxide Synthase
      (iNOS) inhibitor prevented them, which suggests that the NO pathway was involved.
      Decreased IRP activity was also found in monocytes from eight patients with
      inflammation. Interestingly, no late decrease of IRP activity was detected in
      cytokine-treated RE cells from 12 GH patients. Ferritin content was increased 24
      hours after treatment in monocytes from normal subjects but not in monocytes from
      GH patients. The lack of downregulation of IRP activity under inflammatory
      conditions seems to confirm that the control of iron release from RE cells is
      defective in GH.

PMID- 9516160
TI  - Synergism between mycophenolate mofetil and cyclosporine in preventing graft
      versus-host disease among lethally irradiated dogs given DLA-nonidentical
      unrelated marrow grafts.
AB  - Mycophenolate mofetil (MMF) was evaluated either alone or combined with
      cyclosporine (CSP) for preventing graft-versus-host disease (GVHD) in dogs given
      9.2 Gy total body irradiation and DLA-nonidentical unrelated marrow grafts.
      Marrow autograft studies showed gut toxicity as limiting MMF side effects. Four
      groups were studied for GVHD prevention: six dogs in group 1 received MMF 10
      mg/kg twice daily subcutaneously (SC) on days 0 to 27. They died between 8 to 28
      days from infection or GVHD; survival was better than that of 72 controls given
      no immunosuppression (P = .04), but not different from 19 dogs given CSP. Four
      dogs in group 2 received MMF as described, along with CSP at 10 to 15 mg/kg twice
      daily on days 0 to 27. They died at 6 to 98 days from CSP-associated toxicity,
      weight loss, or infection. Nine dogs in group 3 received MMF SC twice daily 6
      mg/kg/d for 3 days, followed by 10 mg/kg twice daily until day 27, along with CSP
      as described; four died between 7 to 106 days with intussusception, infection, or
      GVHD, and five became long-term survivors. Six dogs in group 4 received shortened
      MMF (21 days) and reduced doses of CSP given through day 100. Three died with
      GVHD or infection between days 38 to 119, and three became long-term survivors.
      Results support the notion of synergism between MMF and CSP, as evidenced by
      stable graft-host tolerance in greater than 50% of dogs.

PMID- 9516161
TI  - Lymphoid reconstitution after autologous PBSC transplantation with FACS-sorted
      CD34+ hematopoietic progenitors.
AB  - T-cell and B-cell reconstitution was studied in nine patients who received
      fluorescence activated cell sorter (FACS)-sorted autologous CD34+ hematopoietic
      progenitor cells (HPC). The mean numbers of T cells (CD3+), B cells (CD19+) and
      CD34+ HPC administered to each patient were .004, .002, and 1.8 x 10(6) cells/kg,
      respectively. After high-dose myeloablative chemotherapy (busulfan,
      cyclophosphamide, etoposide) CD34+) HPC were infused and lymphoid reconstitution
      was monitored using flow cytometry and reverse transcriptase-polymerase chain
      reaction (RT-PCR) amplification of VDJ T-cell receptor (TcR) sequences.
      Restoration of normal numbers of peripheral blood T cells and B cells among
      recipients of FACS-sorted CD34+ HPC was delayed compared to recipients of non-T
      cell-depleted PBSC autografts. In both patient groups, the circulating T cells
      were primarily CD4-, CD8+, alphabeta TcR+, and CD45RO+, CD45RA- during the first
      2 months after transplant. Subsequent increases in the frequency of CD45RA+
      CD45RO- T cells occurred at 2 to 3 months after transplant, suggesting maturation
      of CD34+ hematopoietic progenitors to "naive" T cells. Analysis of the TcR
      repertoire after hematopoietic reconstitution demonstrated decreased diversity of
      Vbeta TcR expression associated with global decreases in the absolute number of
      total peripheral blood T cells and most Vbeta TcR+ subsets. Three of nine
      recipients of FACS-sorted CD34+ HPC demonstrated significant increases in the
      percentage of gammadelta+ peripheral T cells and CD5+ B cells at 3 to 9 weeks
      after transplantation, and all patients had transient oligoclonal expansions of T
      cells expressing specific Vbeta TcR. Transplantation with highly purified CD34+
      HPC results in reduced diversity of the peripheral T-cell repertoire during the
      early post-transplant period compared with patients receiving unmanipulated or
      MoAb-depleted transplants.

PMID- 9516163
TI  - Effect of disease stage on clinical outcome after syngeneic bone marrow
      transplantation for relapsing experimental autoimmune encephalomyelitis.
AB  - Relapsing experimental autoimmune encephalomyelitis (R-EAE) is an immune-mediated
      demyelinating central nervous system (CNS) disease. Myeloablation and syngeneic
      bone marrow transplantation (SBMT), when performed at the peak of acute disease
      (day 14), prevented glial scarring and ameliorated the disease severity. In
      contrast, when syngeneic BMT was performed late in chronic phase (day 78),
      significant glial scarring remained and the clinical severity did not differ
      significantly from that of the controls. After SBMT in either the acute or
      chronic phase of disease, the posttransplant immune system remained responsive to
      myelin epitopes as determined by in vitro proliferation and interferon-gamma (IFN
      gamma) production. However, in mice undergoing SBMT, in vivo delayed-type
      hypersensitivity (DTH) responses were significantly decreased while IFN-gamma RNA
      levels and inflammatory infiltrates within the CNS were slightly improved. We
      conclude that failure of SBMT to improve the clinical disease when performed in
      chronic phase may be due to preexisting glial scarring. We also conclude that in
      the absence of glial scarring and irreversible neuronal injury, in vivo DTH
      responses and histology are better predictors of clinical improvement than in
      vitro proliferation or IFN-gamma cytokine production.

PMID- 9516162
TI  - Hurler syndrome: II. Outcome of HLA-genotypically identical sibling and HLA
      haploidentical related donor bone marrow transplantation in fifty-four children.
      The Storage Disease Collaborative Study Group.
AB  - Untreated patients with Hurler syndrome (MPSIH) experience progressive neurologic
      deterioration and early death. Allogeneic bone marrow transplantation (BMT)
      ameliorates or halts this course. The Storage Disease Collaborative Study Group
      was formed to evaluate the effectiveness and toxicity of BMT. Effectiveness was
      defined as engrafted survival with continuing cognitive development. Fifty-four
      patients deficient in leukocyte alpha-L-iduronidase enzyme activity (median age,
      1.8 years; range, 0.4 to 7.9) received high-dose chemotherapy with or without
      irradiation and BMT from HLA-genotypically identical sibling (GIS) or HLA
      haploidentical related (HIR) donors between September 16, 1983 and July 14, 1995;
      all children were included in this report. Thirty-nine of 54 patients (72%)
      engrafted following the first BMT. The probability of grade II to IV acute graft
      versus-host disease (GVHD) at 100 days was 32% for GIS and 55% for HIR patients.
      The probability of extensive chronic GVHD was 0% for GIS and 24% for HIR
      patients. The actuarial probability of survival at 5 years was 64% for all
      patients, 75% for GIS patients, 53% for HIR patients, and 53% for patients with
      donor marrow engraftment. The baseline Mental Developmental Index (MDI) was
      examined both for children less than and greater than 24 months of age at BMT.
      Children transplanted before 24 months had a mean baseline MDI of 78, while those
      transplanted after 24 months had a mean baseline MDI of 63 (P = . 0002). Both
      baseline and post-BMT neuropsychologic data were available for 26 of 30 engrafted
      survivors. Of 14 patients transplanted before 24 months of age, nine demonstrated
      developmental trajectories that were normal or somewhat slower than normal. In
      contrast, of 12 patients transplanted after 24 months of age, only three showed
      developmental trajectories that were normal or somewhat slower than normal (P =
      .01). For children with a baseline MDI greater than 70, there was a significant
      correlation between the MDI at follow-up study and leukocyte alpha-L-iduronidase
      enzyme activity (P = .02). Children were more likely to maintain normal cognitive
      development if they were fully engrafted following BMT from a donor with
      homozygous normal leukocyte alpha-L-iduronidase enzyme activity. Children who
      developed acute GVHD of grade II or worse had significantly poorer cognitive
      outcomes (P < .009). No difference in the post-BMT MDI was observed between
      patients whose preparative therapies did (n = 10; radiation dose, 300 to 1,400
      cGy) or did not (n = 16) include radiation. We conclude that MPSIH patients,
      particularly those less than 24 months of age with a baseline MDI greater than
      70, can achieve a favorable long-term outcome with continuing cognitive
      development and prolonged survival after successful BMT from a related donor with
      homozygous normal enzyme activity.

PMID- 9516164
TI  - Treatment of chronic myeloid leukemia relapsing after allogeneic bone marrow
      transplantation: the case for giving interferon.

PMID- 9516165
TI  - Immune-mediated optic neuritis after unrelated allogeneic bone marrow
      transplantation.

PMID- 9516166
TI  - Hemochromatosis-related mutation detection.

PMID- 9516167
TI  - Fc-RII/CD23 receptor on circulating human eosinophils.

PMID- 9516168
TI  - Importance of T-cell receptor delta-chain gene analysis on CD7+ and CD56+
      myeloid/natural killer cell precursor acute leukemia.

PMID- 9516169
TI  - Intravenous anti-D treatment for immune thrombocytopenic purpura.

PMID- 9516170
TI  - AC133 hematopoietic stem cell antigen: human homologue of mouse kidney prominin
      or distinct member of a novel protein family?

PMID- 9516171
TI  - Chronic graft-versus-host disease and seizure.

PMID- 9516172
TI  - Invited editorial on "Gadolinium prevents high airway pressure-induced
      permeability increases in isolated rat lungs".

PMID- 9516173
TI  - Gadolinium prevents high airway pressure-induced permeability increases in
      isolated rat lungs.
AB  - To determine the initial signaling event in the vascular permeability increase
      after high airway pressure injury, we compared groups of lungs ventilated at
      different peak inflation pressures (PIPs) with (gadolinium group) and without
      (control group) infusion of 20 microM gadolinium chloride, an inhibitor of
      endothelial stretch-activated cation channels. Microvascular permeability was
      assessed by using the capillary filtration coefficient (Kfc), a measure of
      capillary hydraulic conductivity. Kfc was measured after ventilation for 30-min
      periods with 7, 20, and 30 cmH2O PIP with 3 cmH2O positive end-expiratory
      pressure and with 35 cmH2O PIP with 8 cmH2O positive end-expiratory pressure. In
      control lungs, Kfc increased significantly to 1.8 and 3.7 times baseline after 30
      and 35 cmH2O PIP, respectively. In the gadolinium group, Kfc was unchanged from
      baseline (0.060 +/- 0.010 ml . min-1 . cmH2O-1 . 100 g-1) after any PIP
      ventilation period. Pulmonary vascular resistance increased significantly from
      baseline in both groups before the last Kfc measurement but was not different
      between groups. These results suggest that microvascular permeability is actively
      modulated by a cellular response to mechanical injury and that stretch-activated
      cation channels may initiate this response through increases in intracellular
      calcium concentration.

PMID- 9516174
TI  - Pharmacokinetics, immunogenicity, and efficacy of dimeric TNFR binding proteins
      in healthy and bacteremic baboon.
AB  - Immunogenicity, pharmacokinetics, and therapeutic efficacy of three novel dimeric
      soluble tumor necrosis factor (TNF)-receptor I constructs [TNF-binding protein
      (bp)] were evaluated in 28 baboons, 12 of which were healthy and 16 were
      challenged with a lethal Escherichia coli bacteremia. The three constructs
      differed only in the number of extracellular domains of the TNF receptor I and
      were dimerized with polyethylene glycol. Although all three constructs had
      generally similar pharmacokinetics when administered to a naive animal, they
      differed quantitatively in their immunogenicity. Antibodies were detected more
      frequently, and titers were significantly higher (P < 0.05) in both healthy and
      septic baboons that received the 4.0-domain TNF-bp construct, compared with
      animals receiving the 2.6-domain construct. When the TNF-bp constructs were
      administered a second time (21 days later), the half-lives of the three
      constructs were significantly shorter in animals that had an antibody response
      after the first injection. In contrast, all three TNF-bp constructs were equally
      effective at improving outcome, blocking a systemic TNF-alpha response, and
      attenuating the cytokine responses when administered at a dose of 1.0 mg/kg body
      wt 1 h before a lethal E. coli infusion. The findings suggest that immunogenicity
      of TNF-bp constructs can be altered by changing the number of functional domains,
      without affecting their capacity to neutralize TNF-alpha and to abrogate TNF
      mediated pathology.

PMID- 9516175
TI  - Mechanisms of ventilatory inhibition by exogenous dopamine in cats.
AB  - Intravenous injection of dopamine (DA) has consistently been shown to depress
      minute ventilation (VE). Whereas at low dosage (</=10 microgram/kg) this effect
      may be accounted for by inhibition of the carotid sinus nerve chemosensory
      discharge (CSNCD), other mechanisms appear to be involved with large dosage
      (>/=50 microgram/kg). The purpose of this study was to elucidate the mechanisms
      of DA-induced VE depression. The effects of intravenous injection of DA doses
      ranging from 1 to 200 microgram/kg were studied in 18 anesthetized cats. DA was
      injected during air and O2 breathing, after alpha-adrenergic blockade by
      phenoxybenzamine and after baro- and chemodenervation. VE and CSNCD were also
      simultaneously recorded on four occasions. In contrast to that with use of low
      dose DA, VE depression induced by high-dose DA was dissociated from CSNCD,
      persisted during 100% O2 breathing, and was significantly correlated with the
      rise in arterial blood pressure. Although blunted, VE depression was still
      present after complete chemo- and barodenervation but was suppressed by blocking
      of the concomitant vasoconstriction with phenoxybenzamine. It is concluded that
      reflexes of circulatory origin contribute to the VE depression induced by large
      dose DA, in addition to its effects on arterial chemoreceptors. The contribution
      of baroreceptor stimulation and peripheral vasoconstriction is discussed.

PMID- 9516176
TI  - Inhibitory effect of inhaled wood smoke on the discharge of pulmonary stretch
      receptors in rats.
AB  - We investigated the inhibition of slowly adapting pulmonary stretch receptors
      (PSRs) by inhaled wood smoke. Impulses were recorded from PSRs in 68
      anesthetized, open-chest, and artificially ventilated rats. Eighty-one of one
      hundred five PSRs were inhibited within one or two breaths when 6 ml of wood
      smoke were delivered into the lungs. As a group (n = 105), PSR activity
      significantly decreased from a baseline of 19.0 +/- 1.3 (SE) to a lowest level of
      12.9 +/- 1.2 impulses/breath at the fourth or fifth breath after smoke delivery.
      This afferent inhibition usually persisted for 5-18 breaths. In contrast, smoke
      delivery did not affect transpulmonary pressure. Delivery of gas-phase smoke or a
      hypercapnic gas mixture containing CO2 at a concentration (15%) matching that in
      the smoke produced a nearly identical inhibition in the same PSRs (n = 10). This
      afferent inhibition was largely prevented by pretreatment with acetazolamide (an
      inhibitor of carbonic anhydrase; n = 10) but was not affected by pretreatment
      with the vehicle for acetazolamide (n = 8) or isoproterenol (a bronchodilator; n
      = 10). These results suggest that 1) an increase in H+ concentration resulting
      from hydration of CO2 in the smoke may be responsible for the inhibitory effect
      of wood smoke on the discharge of PSRs and 2) changes in lung mechanics are not
      the cause of this afferent inhibition.

PMID- 9516177
TI  - Functional magnetic stimulation of expiratory muscles: a noninvasive and new
      method for restoring cough.
AB  - The purpose of this study was to assess the effectiveness of functional magnetic
      stimulation (FMS) for producing expiratory function in normal human subjects.
      Twelve able-bodied normal subjects were recruited for this study. FMS of the
      expiratory muscles was performed by using a magnetic stimulator and placing the
      magnetic coil along the lower thoracic spine. Results showed that peak expired
      pressure, volume, and flow rate generated by FMS at the end of normal inspiration
      (102.5 +/- 13.62 cmH2O, 1.6 +/- 0.16 liters, and 4.8 +/- 0.35 l/s, respectively)
      were comparable to their voluntary maximal levels (P > 0.1). The optimal coil
      placement was between T7 and T11, and the optimal stimulation parameters were a
      frequency of 25 Hz and 70-80% of maximal intensity. We conclude that 1) FMS of
      the lower thoracic nerves in normal subjects resulted in a significant expiratory
      function comparable to their voluntary maximum; 2) FMS was noninvasive and was
      well tolerated by all subjects; and 3) FMS may be useful to produce cough in
      patients in critical care or perioperative settings, or in patients with
      neurological disorders.

PMID- 9516178
TI  - Catecholamine response during 12 days of high-altitude exposure (4, 300 m) in
      women.
AB  - We have previously demonstrated that acclimatization to high altitude elicits
      increased sympathetic nerve activity in men. The purpose of this investigation
      was to determine 1) whether women respond in a similar manner as found previously
      in men and 2) the extent to which menstrual cycle phase influences this response.
      Sixteen eumenorrheic women (age, 23.6 +/- 1.2 yr; weight, 56.2 +/- 4. 3 kg) were
      studied at sea level and during 12 days of high-altitude exposure (4,300 m) in
      either their follicular (F; n = 11) or luteal (L; n = 5) phase. Twenty-four-hour
      urine samples were collected at sea level and during each day at altitude.
      Catecholamines were determined by high-performance liquid chromatography with
      electrochemical detection. Compared with sea-level values, urinary norepinephrine
      excretion increased significantly during altitude exposure, peaking on days 4-6.
      Thereafter, levels remained constant throughout the duration of altitude
      exposure. The magnitude of this increase was similar between the F (138%) and L
      (93%) phase. Urinary epinephrine levels were elevated on day 2 of altitude
      exposure compared with sea-level values for both F and L subjects (93%).
      Thereafter, urinary epinephrine excretion returned to sea-level values, and no
      differences were found between F and L subjects. Plasma catecholamine content was
      consistent with urinary values and supports the concept of an elevation in
      sympathetic activity over time at altitude. Mean and diastolic blood pressure as
      well as heart rate adjustments to high altitude correlated significantly with
      urinary norepinephrine excretion rates. It was concluded that 1) urinary and
      plasma catecholamine responses to 12 days of high-altitude exposure in women are
      similar to those previously documented to occur for men; 2) whereas no
      differences in catecholamine levels were observed between F- and L-phase
      assignments, for a given urinary norepinephrine excretion rate, blood pressure
      and heart rates were lower for F vs. L subjects; and 3) several cardiovascular
      adaptations associated with high-altitude exposure correlated with 24-h urinary
      norepinephrine excretion rates and thus sympathetic nerve activity.

PMID- 9516179
TI  - Central interaction between carotid baroreceptors and skeletal muscle receptors
      inhibits sympathoexcitation.
AB  - To determine the potential of an inhibitory interaction between the carotid sinus
      baroreflex (CSB) and the exercise pressor reflex (EPR), both pathways were
      activated to produce sympathoexcitation. It was hypothesized that, under
      conditions when the baroreflex increased sympathetic outflow, the interaction
      between CSB and EPR would be inhibitory. Bilateral carotid occlusion (BCO),
      electrically induced muscle contraction (EMC), and passive muscle stretch (PMS)
      were used to evoke sympathoexcitation. BCO decreased sinus pressure 50 +/- 5
      mmHg, and the levels of muscle tension generated by EMC and PMS were 7 +/- 2 and
      8 +/- 1 kg, respectively. This resulted in significant increases in mean arterial
      pressure (MAP) of 55 +/- 9, 50 +/- 7, and 50 +/- 6 mmHg (P = not significant, BCO
      vs. EMC vs. PMS) and in heart rate (HR) of 7 +/- 2, 19 +/- 4, and 17 +/- 2
      beats/min (P < 0. 05, BCO vs. EMC and PMS). When BCO was combined with EMC or
      PMS, the reflex increase in MAP was augmented (80 +/- 8 and 79 +/- 10 mmHg;
      BCO+EMC and BCO+PMS, respectively; P < 0.05). However, summation of the
      individual MAP responses was greater than the response evoked during coactivation
      (106 +/- 11 and 103 +/- 12 mmHg, respectively, P < 0.05). Because summing the
      individual blood pressure responses exceeded the response during coactivation,
      the net effect was that the CSB and EPR interacted in an occlusive manner. In
      contrast, summation of the individual chronotropic responses was the same as the
      response evoked during coactivation. Moreover, there was no difference in
      summation of the individual MAP or HR responses when muscle afferents were
      activated by either EMC or PMS. In conclusion, the interaction between the CSB
      and the EPR in control of MAP was occlusive when both reflexes were stimulated to
      evoke sympathoexcitation. However, summation of the reflex changes in HR was
      simply additive.

PMID- 9516180
TI  - Absence of myofibrillar creatine kinase and diaphragm isometric function during
      repetitive activation.
AB  - Creatine kinase (CK) provides ATP buffering in skeletal muscle and is expressed
      as 1) cytosolic myofibrillar CK (M-CK) and 2) sarcomeric mitochondrial CK
      (ScCKmit) isoforms that differ in their subcellular localization. We compared the
      isometric contractile and fatigue properties of 1) control CK-sufficient (Ctl),
      2) M-CK-deficient (M-CK[-/-]), and 3) combined M-CK/ScCKmit-deficient null mutant
      (CK[-/-]) diaphragm (Dia) to determine the effect of the absence of M-CK activity
      on Dia performance in vitro. Baseline contractile properties were comparable
      across groups except for specific force, which was approximately 16% lower in CK[
      /-] Dia compared with M-CK[-/-] and Ctl Dia. During repetitive activation (40 Hz,
      (1)/(3) duty cycle), force declined in all three groups. This decline was
      significantly greater in CK[-/-] Dia compared with Ctl and M-CK[-/-] Dia. The
      pattern of force decline did not differ between M-CK[-/-] and Ctl Dia. We
      conclude that Dia isometric muscle function is not absolutely dependent on the
      presence of M-CK, whereas the complete absence of CK acutely impairs isometric
      force generation during repetitive activation.

PMID- 9516181
TI  - High-frequency oscillatory ventilation in neonatal RDS: initial volume
      optimization and respiratory mechanics.
AB  - To determine whether initial lung volume optimization influences respiratory
      mechanics, which could indicate the achievement of optimal volume, we studied 17
      premature infants with respiratory distress syndrome (RDS) assisted by high
      frequency oscillatory ventilation. The continuous distending pressure (CDP) was
      increased stepwise from 6-8 cmH2O up to optimal CDP (OCDP), i.e., that allowing
      good oxygenation with the lowest inspired O2 fraction. Respiratory system
      compliance (Crs) and resistance were concomitantly measured. Mean OCDP was 16.5
      +/- 1.2 cmH2O. Inspired O2 fraction could be reduced from an initial level of
      0.73 +/- 0.17 to 0.33 +/- 0.07. However, Crs (0.45 +/- 0.14 ml . cmH2O-1 . kg-1
      at starting CDP point) remained unchanged through lung volume optimization but
      appeared inversely related to OCDP. Similarly, respiratory system resistance was
      not affected. We conclude that there is a marked dissociation between oxygenation
      improvement and Crs profile during the initial phase of lung recruitment by early
      high-frequency oscillatory ventilation in infants with RDS. Thus optimal lung
      volume cannot be defined by serial Crs measurement. At the most, low initial Crs
      suggests that higher CDP will be needed.

PMID- 9516182
TI  - Effect of muscle glycogen content on exercise-induced changes in muscle T2 times.
AB  - Effects of gastrocnemius glycogen (Gly) concentration on changes in transverse
      relaxation time (T2; ms) were studied after 5-min plantar flexion at 25% of
      maximum voluntary contraction (MVC). Gastrocnemius Gly, phosphorus metabolites,
      and T2 were measured in seven subjects by using interleaved 13C/31P magnetic
      resonance spectroscopy (MRS) at 4.7 T and magnetic resonance imaging (MRI; 1.5
      T). After baseline MRS/MRI, subjects exercised for 5 min at 25% of MVC and were
      reexamined (MRS/MRI). Subjects then performed approximately 15 min of single-leg
      toe raises (50 +/- 2% of MVC), depleting gastrocnemius Gly by 43%. After a 1-h
      rest (for T2 return to baseline), subjects repeated the 5-min protocol, followed
      by a final MRI/MRS. After the initial 5-min protocol, T2 values increased by 5.9
      +/- 0.8 ms (29.9 +/- 0.4 to 35.8 +/- 0.6 ms), whereas Gly did not change
      significantly (70.5 +/- 6.8 to 67.6 +/- 7.4 mM). After 15 min of toe raises,
      gastrocnemius Gly was reduced to 40.4 +/- 5.3 mM (P </= 0. 01), recovering to
      45.8 +/- 5.3 mM (P </= 0.05) during a 1-h rest. After the second 5-min bout of
      plantar flexion (reduced Gly at 25% of MVC), T2 values increased by 5.0 +/- 0.8
      ms (30.4 to 35.4 ms), whereas muscle Gly rose to 57.6 +/- 5.3 mM. We conclude
      that muscle Gly concentration per se does not affect exercise-induced T2
      increases in the human gastrocnemius.

PMID- 9516183
TI  - Sustained submaximal exercise does not alter the integrity of the lung blood-gas
      barrier in elite athletes.
AB  - The extreme thinness of the pulmonary blood-gas barrier results in high
      mechanical stresses in the capillary wall when the capillary pressure rises
      during exercise. We have previously shown that, in elite cyclists, 6-8 min of
      maximal exercise increase blood-gas barrier permeability and result in higher
      concentrations of red blood cells, total protein, and leukotriene B4 in
      bronchoalveolar lavage (BAL) fluid compared with results in sedentary controls.
      To test the hypothesis that stress failure of the barrier only occurs at the
      highest level of exercise, we performed BAL in six healthy athletes after 1 h of
      exercise at 77% of maximal O2 consumption. Controls were eight normal nonathletes
      who did not exercise before BAL. In contrast with our previous study, we did not
      find higher concentrations of red blood cells, total protein, and leukotriene B4
      in the exercising athletes compared with control subjects. However, higher
      concentrations of surfactant apoprotein A and a higher surfactant apoprotein A-to
      phospholipid ratio were observed in the athletes performing prolonged exercise,
      compared with both the controls and the athletes from our previous study. These
      results suggest that, in elite athletes, the integrity of the blood-gas barrier
      is altered only at extreme levels of exercise.

PMID- 9516184
TI  - Exposing guinea pigs to ozone for 1 wk enhances responsiveness of rapidly
      adapting receptors.
AB  - Acute exposure to ozone causes changes in breathing pattern and lung function
      which may be caused in part by stimulation of rapidly adapting receptors (RARs).
      The consequences of repeated daily ozone exposure on RAR responsiveness are
      unknown, although ozone-induced changes in pulmonary function diminish with
      repeated exposure. Accordingly, we investigated whether repeated daily ozone
      exposure diminishes the general responsiveness of RARs. Guinea pigs (n = 30) were
      exposed to 0.5 parts/million ozone or filtered air (8 h/day for 7 days). The
      animals were then anesthetized, and RAR impulse activity, dynamic compliance
      (Cdyn), and lung resistance were recorded at baseline and in response to four
      stimuli: substance P, methacholine, hyperinflation, and removal of positive end
      expiratory pressure. Repeated daily ozone exposure exaggerated RAR responses to
      substance P, methacholine, and hyperinflation without causing physiologically
      relevant effects on baseline or substance P- and methacholine-induced changes in
      Cdyn and lung resistance. Because agonist-evoked changes in RAR activity preceded
      Cdyn changes, the data suggest that repeated daily ozone exposure enhances RAR
      responsiveness via a mechanism other than changes in Cdyn.

PMID- 9516185
TI  - Differential respiratory muscle recruitment induced by clonidine in awake goats.
AB  - The purpose of this study was to test the hypothesis that dysrhythmic breathing
      induced by the alpha2-agonist clonidine is accompanied by differential
      recruitment of respiratory muscles. In adult goats (n = 14) electromyographic
      (EMG) measurements were made from inspiratory muscles (diaphragm and parasternal
      intercostal) and expiratory muscles [triangularis sterni (TS) and transversus
      abdominis (Abd)]. EMG of the thyroarytenoid (TA) muscle was used as an index of
      upper airway (glottal) patency. Peak EMG activities of all spinal inspiratory and
      expiratory muscles were augmented by central and peripheral chemoreceptor
      stimuli. Phasic TA was apparent in the postinspiratory phase of the breathing
      cycle under normoxic conditions. During dysrhythmic breathing episodes induced by
      clonidine, TS and Abd activities were attenuated or abolished, whereas diaphragm
      and parasternal intercostal activities were unchanged. There was no tonic
      activation of TS or Abd EMG during apneas; however, TA activity became tonic
      throughout the apnea. We conclude that 1) alpha2-adrenoceptor stimulation results
      in differential recruitment of respiratory muscles during respiratory
      dysrhythmias and 2) apneas are accompanied by active glottic closure in the awake
      goat.

PMID- 9516186
TI  - Early cerebral metabolic and electrophysiological recovery during controlled
      hypoxemic resuscitation in piglets.
AB  - We tested the hypothesis that controlled hypoxemic resuscitation improves early
      cerebral metabolic and electrophysiological recovery in hypoxic newborn piglets.
      Severely hypoxic anesthetized piglets were randomly divided into three
      resuscitation groups: hypoxemic, 21% O2, and 100% O2 groups (8 in each group).
      The hypoxemic group was mechanically ventilated with 12-18% O2 adjusted to
      achieve a cerebral venous O2 saturation of 17-23% (baseline; 45 +/- 1%). Base
      excess (BE) reached -22 +/- 1 mM at the end of hypoxia. During a 2-h
      resuscitation period, no significant differences in time to recovery of
      electroencephalography (EEG), quality of EEG at recovery, or extracellular
      hypoxanthine concentrations in the cerebral cortex and striatum were found among
      the groups. BE and plasma hypoxanthine, however, normalized significantly more
      slowly during controlled hypoxemic resuscitation than during resuscitation with
      21 or 100% O2. We conclude that early brain recovery during controlled hypoxemic
      resuscitation was as efficient as, but not superior to, recovery during
      resuscitation with 21 or 100% O2. The systemic metabolic recovery from hypoxia,
      however, was delayed during controlled hypoxemic resuscitation.

PMID- 9516187
TI  - Production and absorption of nitric oxide gas in the nose.
AB  - Some nitric oxide gas (NO) produced in the sinuses and nasal cavity is absorbed
      before leaving the nose. To measure production and absorption, we introduced NO
      at different concentrations into one nostril while sampling the NO leaving the
      opposite nostril with the soft palate closed. The quantity of NO gas produced in
      six normal subjects (amount leaving plus the amount absorbed) averaged 352 nl/min
      and was the same at gas flows ranging from 8 to 347 ml/min and at 10 l/min. An
      absorption coefficient A was calculated by dividing the amount of NO absorbed by
      the concentration leaving the nose. A ranged from 17 ml/min at a nasal gas flow
      of 8 ml/min to an A of 24 ml/min at a nasal gas flow of 347 ml/min. The
      calculated rates of production and absorption did not change when gas flow rate
      was increased, suggesting diffusion equilibrium. The amount of uptake of NO in
      the nasal mucosa can be explained by its solubility coupled with tissue and blood
      reactivity.

PMID- 9516189
TI  - Time course of sympathovagal imbalance and left ventricular dysfunction in
      conscious dogs with heart failure.
AB  - To elucidate the time course of sympathovagal balance and its relationship to
      left ventricular function in heart failure, we serially evaluated left
      ventricular contractility and relaxation and autonomic tone in 11 conscious dogs
      with tachycardia-induced heart failure. We determined a dynamic map of
      sympathetic and parasympathetic modulation by power spectral analysis of heart
      rate variability. The left ventricular peak +dP/dt substantially fell from 3,364
      +/- 338 to 1,959 +/- 318 mmHg/s (P < 0.05) on the third day and declined
      gradually to 1,783 +/- 312 mmHg/s at 2 wk of rapid ventricular pacing. In
      contrast, the time constant of left ventricular pressure decay and end-diastolic
      pressure increased gradually from 25 +/- 4 to 47 +/- 5 ms (P < 0.05) and from 10
      +/- 2 to 21 +/- 3 mmHg (P < 0.05), respectively, at 2 wk of pacing. The high
      frequency component (0.15-1.0 Hz), a marker of parasympathetic modulation,
      decreased from 1,928 +/- 1,914 to 62 +/- 68 x 10(3) ms2 (P < 0.05) on the third
      day and further to 9 +/- 12 x 10(3) ms2 (P < 0.05) at 2 wk. Similar to the time
      course of left ventricular diastolic dysfunction, plasma norepinephrine levels
      and the ratio of low (0.05- to 0.15-Hz)- to high-frequency component increased
      progressively from 135 +/- 50 to 532 +/- 186 pg/ml (P < 0.05) and from 0.06 +/-
      0.06 to 1.12 +/- 1.01 (P < 0.05), respectively, at 2 wk of pacing. These cardiac
      and autonomic dysfunctions recovered gradually toward the normal values at 2 wk
      after cessation of pacing. Thus a parallel decline in left ventricular
      contractility with parasympathetic influence and a parallel progression in left
      ventricular diastolic dysfunction with sympathoexcitation suggest a close
      relationship between cardiac dysfunction and autonomic dysregulation during
      development of heart failure.

PMID- 9516188
TI  - Exercise training increases K+-channel contribution to regulation of coronary
      arterial tone.
AB  - The present study examined whether regulation of coronary tone in conduit
      arteries (>1.0 mm ID) is altered by exercise training. Yucatan miniature swine
      were treadmill trained for 16-20 wk (Ex) and compared with sedentary counterparts
      (Sed). Endothelium-denuded arterial rings were stretched to optimal length and
      allowed to equilibrate for 60 min. Inhibition of either Ca2+-activated channels
      [1 mM tetraethylammonium (TEA) or 10 nM iberiotoxin (IBTX)] or voltage-dependent
      K+ channels [1 mM 4-aminopyridine (4-AP)] significantly increased resting tension
      in both groups; however, the effect of all K+-channel blockers was greater in Ex.
      Addition of 1 mM sodium nitroprusside reduced resting tension in both groups,
      confirming the presence of active basal tone; however, sodium nitroprusside
      sensitive tone was increased approximately twofold in Ex compared with Sed group.
      Perforated patch-clamp experiments on isolated smooth muscle cells demonstrated
      no effect of exercise training on whole cell TEA-sensitive, 4-AP-sensitive, or
      basal K+ current. Similarly, whereas TEA, 4-AP, and IBTX all decreased resting
      membrane potential, there was no difference in depolarization between groups. The
      greater effect of TEA on resting tension in Ex could be mimicked in Sed by
      addition of the Ca2+-channel agonist BAY K 8644. In conclusion, the greater
      response to K+-channel blockers after exercise training is consistent with an
      increased contribution of K+ channels to regulation of basal tone in conduit
      coronary arteries. The lack of an effect of training on K+ current
      characteristics or membrane potential responses in isolated cells suggests that a
      requisite factor for enhanced K+-channel activation in arteries from Ex, possibly
      stretch, is absent in isolated cells.

PMID- 9516190
TI  - Polycythemic responses to hypoxia: molecular and genetic mechanisms of chronic
      mountain sickness.
AB  - We examined erythropoietin (EPO) gene expression and EPO production during
      hypoxia in two Sprague-Dawley rat strains with divergent polycythemic responses
      to hypoxia. Hilltop (H) rats develop severe polycythemia, severe hypoxemia, and
      pulmonary artery hypertension. The H rats often die from a syndrome
      indistinguishable from chronic mountain sickness (CMS) in humans. Madison (M)
      rats develop polycythemia and pulmonary artery hypertension that is modest and
      suffer no excess mortality. We tested the hypothesis that these rat strains have
      different stimulus-response characteristics governing EPO production. Rats of
      each strain were exposed to hypoxia (0.5 atm, 73 Torr inspired PO2), and renal
      tissue EPO mRNA and EPO levels, plasma EPO, ventilation, arterial and renal
      venous blood gases, and indexes of renal function were measured at fixed times
      during a 30-day hypoxic exposure. During extended hypoxic exposure, H rats had
      significantly elevated renal EPO mRNA, renal EPO, and plasma EPO levels compared
      with M rats. Ventilatory responses and indexes of renal function were similar in
      the strains during the hypoxic exposure. H rats had greater arterial hypoxemia
      from the onset of hypoxia and more severe renal tissue hypoxemia and greater
      polycythemia after 14 days of hypoxic exposure. When EPO responses were expressed
      as functions of renal venous PO2, the two strains appeared to lie on the same
      dose-response curves, but the responses of H rats were shifted along the curve
      toward more hypoxic values. We conclude that H rats have significantly greater
      polycythemia secondary to poorer renal tissue oxygenation, but the stimulus
      response characteristics governing EPO gene expression and EPO production do not
      seem to differ between M and H rats. Finally, the regulation of EPO levels during
      hypoxia occurs primarily at the transcriptional level.

PMID- 9516192
TI  - Isotonic contractile and fatigue properties of developing rat diaphragm muscle.
AB  - Postnatal transitions in myosin heavy chain (MHC) isoform expression were found
      to be associated with changes in both isometric and isotonic contractile
      properties of rat diaphragm muscle (Diam). Expression of MHCneo predominated in
      neonatal Diam fibers but was usually coexpressed with MHCslow or MHC2A isoforms.
      Expression of MHCneo disappeared by day 28. Expression of MHC2X and MHC2B emerged
      at day 14 and increased thereafter. Associated with these MHC transitions in the
      Diam, maximum isometric tetanic force (Po), maximum shortening velocity, and
      maximum power output progressively increased during early postnatal development.
      Maximum power output of the Diam occurred at approximately 40% Po at days 0 and 7
      and at approximately 30% Po in older animals. Susceptibility to isometric and
      isotonic fatigue, defined as a decline in force and power output during
      repetitive activation, respectively, increased with maturation. Isotonic
      endurance time, defined as the time for maximum power output to decline to zero,
      progressively decreased with maturation. In contrast, isometric endurance time,
      defined as the time for force to decline to 30-40% Po, remained > 300 s until
      after day 28. We speculate that with the postnatal transition to MHC2X and MHC2B
      expression energy requirements for contraction increase, especially during
      isotonic shortening, leading to a greater imbalance between energy supply and
      demand.

PMID- 9516191
TI  - Effects of mode and carbohydrate on the granulocyte and monocyte response to
      intensive, prolonged exercise.
AB  - The influence of exercise mode and 6% carbohydrate (C) vs. placebo (P) beverage
      ingestion on granulocyte and monocyte phagocytosis and oxidative burst activity
      (GMPOB) after prolonged and intensive exertion was measured in 10 triathletes.
      The triathletes acted as their own controls and ran or cycled for 2.5 h at
      approximately 75% maximal O2 uptake, ingesting C or P (4 total sessions, random
      order, with beverages administered in double-blind fashion). During the 2. 5-h
      exercise bouts, C or P (4 ml/kg) was ingested every 15 min. Five blood samples
      were collected (15 min before exercise, immediately after exercise, and 1.5, 3,
      and 6 h after exercise). The pattern of change over time for GMPOB was
      significantly different between C and P conditions (P </= 0.05), with
      postexercise values lower during the C trials. Little difference was measured
      between running and cycling modes. C relative to P ingestion (but not exercise
      mode) was associated with higher plasma levels of glucose and insulin, lower
      plasma levels of cortisol and growth hormone, and lower blood neutrophil and
      monocyte cell counts. These data indicate that C vs. P ingestion is associated
      with higher plasma glucose levels, an attenuated cortisol response, and lower
      GMPOB.

PMID- 9516193
TI  - HSP70 expression in the CNS in response to exercise and heat stress in rats.
AB  - We have previously documented the regional distribution of 70-kDa heat shock
      protein (HSP70) in brains of rats made hyperthermic by brief exposure to high
      powered microwaves (HPM; 2.06 GHz). We now compare HSP70 expression induced by
      HPM exposure to that induced by exertional and/or environmental heat stress. Rats
      were chronically implanted with a temperature probe guide in the hypothalamic
      region of the brain (Tbr). After recovery, the following treatment groups were
      examined: HPM; sham exposed; treadmill exercise at room temperature (24 degreesC;
      Ex-1); treadmill exercise in a warm environment (34 degreesC; Ex-2); and
      sedentary groups (Sed-1 and Sed-2), in which ambient temperature was adjusted so
      that the Tbr mimicked the Tbr in the corresponding exercise groups. Significant
      HSP70 expression occurred only in the hyperthermic (Ex-2, Sed-2, and HPM) groups.
      The pattern of HSP70 expression was similar among Ex-2 and Sed-2 rats but
      differed from that in HPM rats. We conclude that 1) the pattern of HSP70
      expression differs between HPM and nonmicrowave heating, and 2) exercise alone
      was not sufficient to induce central HSP70 expression.

PMID- 9516194
TI  - Pulmonary blood flow redistribution by increased gravitational force.
AB  - This study was undertaken to assess the influence of gravity on the distribution
      of pulmonary blood flow (PBF) using increased inertial force as a perturbation.
      PBF was studied in unanesthetized swine exposed to -Gx (dorsal-to-ventral
      direction, prone position), where G is the magnitude of the force of gravity at
      the surface of the Earth, on the Armstrong Laboratory Centrifuge at Brooks Air
      Force Base. PBF was measured using 15-micron fluorescent microspheres, a method
      with markedly enhanced spatial resolution. Each animal was exposed randomly to 
      1, -2, and -3 Gx. Pulmonary vascular pressures, cardiac output, heart rate,
      arterial blood gases, and PBF distribution were measured at each G level.
      Heterogeneity of PBF distribution as measured by the coefficient of variation of
      PBF distribution increased from 0.38 +/- 0.05 to 0.55 +/- 0.11 to 0.72 +/- 0.16
      at -1, -2, and -3 Gx, respectively. At -1 Gx, PBF was greatest in the ventral and
      cranial and lowest in the dorsal and caudal regions of the lung. With increased 
      Gx, this gradient was augmented in both directions. Extrapolation of these values
      to 0 G predicts a slight dorsal (nondependent) region dominance of PBF and a
      coefficient of variation of 0.22 in microgravity. Analysis of variance revealed
      that a fixed component (vascular structure) accounted for 81% and nonstructure
      components (including gravity) accounted for the remaining 19% of the PBF
      variance across the entire experiment (all 3 gravitational levels). The results
      are inconsistent with the predictions of the zone model.

PMID- 9516195
TI  - Systemic and myocardial hemodynamics during periodic obstructive apneas in
      sedated pigs.
AB  - The effects of periodic obstructive apneas on systemic and myocardial
      hemodynamics were studied in nine preinstrumented sedated pigs under four
      conditions: breathing room air (RA), breathing 100% O2, breathing RA after
      critical coronary stenosis (CS) of the left anterior descending coronary artery,
      and breathing RA after autonomic blockade with hexamethonium (Hex). Apneas with
      RA increased mean arterial pressure (MAP; from baseline 103.0 +/- 3.5 to late
      apnea 123.6 +/- 7.0 Torr, P < 0.001) and coronary blood flow (CBF; late apnea
      193.9 +/- 22.9% of baseline, P < 0.001) but decreased cardiac output (CO; from
      baseline 2.97 +/- 0.15 to late apnea 2.39 +/- 0.19 l/min, P < 0.001). Apneas with
      O2 increased MAP (from baseline 105.1 +/- 4.6 to late apnea 110.7 +/- 4.8 Torr, P
      < 0. 001). Apneas with CS produced similar increases in MAP as apneas with RA but
      greater decreases in CO (from baseline 3.03 +/- 0.19 to late apnea 2.1 +/- 0.15
      l/min, P < 0.001). In LAD-perfused myocardium, there was decreased segmental
      shortening (baseline 11.0 +/- 1.5 to late apnea 7.6 +/- 2.0%, P < 0.01) and
      regional intramyocardial pH (baseline 7.05 +/- 0.03 to late apnea 6.72 +/- 0. 11,
      P < 0.001) during apneas with CS but under no other conditions. Apneas with Hex
      increased to the same extent as apneas with RA. Myocardial O2 demand remained
      unchanged during apnea relative to baseline. We conclude that obstructive apnea
      induced changes in left ventricular afterload and CO are secondary to autonomic
      mediated responses to hypoxemia. Increased CBF during apneas is related to
      regional metabolic effects of hypoxia and not to autonomic factors. In the
      presence of limited coronary flow reserve, decreased O2 supply during apneas can
      lead to myocardial ischemia, which in turn adversely affects left ventricular
      function.

PMID- 9516196
TI  - Effects of HCl-pepsin laryngeal instillations on upper airway patency-maintaining
      mechanisms.
AB  - Gastroesophageal reflux has been indicated as an etiopathological factor in
      disorders of the upper airway. Upper airway collapsing pressure stimulates
      pressure-responsive laryngeal receptors that reflexly increase the activity of
      upper airway abductor muscles. We studied, in anesthetized dogs, the effects of
      repeated laryngeal instillations of HCl-pepsin (HCl-P; pH = 2) on the response of
      laryngeal afferent endings and the posterior cricoarytenoid muscle (PCA) to
      negative pressure. The effect of negative pressure on receptor discharge or PCA
      activity was evaluated by comparing their response to upper airway (UAO) and
      tracheal occlusions (TO). It is only during UAO, but not during TO, that the
      larynx is subjected to negative transmural pressure. HCl-P instillation decreased
      the rate of discharge during UAO of the 10 laryngeal receptors studied from 56.4
      +/- 10.9 (SE) to 38.2 +/- 9.2 impulses/s (P < 0.05). With UAO, the peak PCA
      moving time average, normalized by dividing it by the peak values of esophageal
      pressure, decreased after six HCl-P trials from 4.29 +/- 0.31 to 2.23 +/- 0.18 (n
      = 6; P < 0.05). The responses to TO of either receptors or PCA remained
      unaltered. We conclude that exposure of the laryngeal mucosa to HCl-P solutions,
      as it may occur with gastroesophageal reflux, impairs the patency-maintaining
      mechanisms provided by laryngeal sensory feedback. Inflammatory and necrotic
      alterations of the laryngeal mucosa are likely responsible for these effects.

PMID- 9516197
TI  - Aerobic exercise maintains regional bone mineral density during weight loss in
      postmenopausal women.
AB  - This study examines the effects of weight loss by caloric restriction (WL) and
      aerobic exercise plus weight loss (AEx+WL) on total and regional bone mineral
      density (BMD) in older women. Healthy, postmenopausal women [age 63 +/- 1 (SE)
      yr] not on hormone-replacement therapy underwent 6 mo of WL (n = 15) consisting
      of dietary counseling one time per week with a caloric deficit (250-350 kcal/day)
      or AEx+WL (n = 15) consisting of treadmill exercise three times per week in
      addition to the weight loss. Maximal aerobic capacity increased only in the
      AEx+WL group (P < 0. 001). Body weight, percent fat, and fat mass decreased
      similarly in both groups (P < 0.005), with no changes in fat-free mass. Total
      body BMD (by dual-energy X-ray absorptiometry) decreased in both groups (P <
      0.05). Femoral neck, Ward's triangle, and greater trochanter BMD decreased in the
      WL group (P </= 0.05) but were not significantly different after AEx+WL. L2-L4
      BMD did not significantly change in either group. Thus WL and AEx+WL both result
      in losses of total body BMD; however, AEx+WL appears to prevent the loss in
      regional BMD seen with WL alone in healthy, older women. This suggests that the
      addition of exercise to weight-loss programs may reduce the risk for bone loss.

PMID- 9516198
TI  - Diet-induced insulin resistance precedes other aspects of the metabolic syndrome.
AB  - This study was designed to examine the effects of a high-fat refined-sugar (HFS)
      or a low-fat complex-carbohydrate (LFCC) diet on insulin-stimulated skeletal
      muscle glucose transport, plasma insulin, blood pressure, plasma triglycerides,
      plasma glycerol, body weight, and body fat in female Fischer rats. Insulin
      stimulated glucose transport was significantly reduced in the HFS group at 2 wk,
      2 mo, and 2 yr, whereas serum insulin was significantly elevated at all time
      points. Blood pressure was not significantly elevated in the HFS group until 12
      mo, and all HFS animals were hypertensive by 18 mo. Glycerol, triglycerides, and
      abdominal fat cell size were not significantly different at 2 wk but were
      significantly elevated in the HFS rats at 2 and 6 mo. Body weight was similar in
      both groups until 20 wk on the diet, when the HFS rats started to gain more
      weight. These results demonstrate that insulin resistance and hyperinsulinemia
      occur before the other manifestations of the metabolic syndrome and that diet,
      not obesity, is the underlying cause.

PMID- 9516199
TI  - Surfactant replacement increases compliance in premature lamb lungs during
      partial liquid ventilation in situ.
AB  - Treatments available to improve compliance in surfactant-deficient states include
      exogenous surfactant (ES) and either partial (PLV) or total liquid ventilation
      (TLV) with perfluorochemical (PFC). Because of the additional air-lung and air
      PFC interfaces introduced during PLV compared with TLV, we hypothesized that
      compliance would be worse during PLV than during TLV. Because surfactant is able
      to reduce interfacial tension between air and lung as well as between PFC and
      lung, we further hypothesized that compliance would improve with surfactant
      treatment before PLV. In excised preterm lamb lungs, we used Survanta for
      surfactant replacement and perflubron as the PFC. Compliance during PLV was
      intermediate between TLV and gas inflation, both with and without surfactant.
      Surfactant improved compliance during PLV, compared with PLV alone. Because of
      the force-balance equation governing the behavior of immiscible droplets on
      liquid surfaces, we predict that PFC droplets spread during PLV to cover the
      alveolar surface in surfactant-deficient lungs during most of lung inflation and
      deflation but that the PFC would retract into droplets in surfactant-sufficient
      lungs, except at end inspiration.

PMID- 9516201
TI  - Energy metabolism in sedentary and active 49- to 70-yr-old women.
AB  - This study examined differences between long-term exercising (LE) and long-term
      nonexercising (LNE) women [n = 24; age 56.4 +/- 6.2 (SD) yr] for resting
      metabolic rate (RMR) and energy expenditure in the free-living state by using
      doubly labeled water (DLW). There was a statistically significant difference (P =
      0.0002) between the 12 LE (94.85 +/- 8.44 kJ . kg-1 . day-1) and 12 LNE (81.16 +/
      6.62 kJ . kg-1 . day-1) for RMR, but this difference was only marginally
      significant (P = 0.06) when the data (MJ/day) were subjected to an analysis of
      covariance with fat-free mass as the covariate. The DLW data indicated that the
      eight most active LE (12.99 +/- 3.58 MJ/day) expended significantly (P = 0.01)
      more energy than did the eight least active LNE (9.30 +/- 1.15 MJ/day). Energy
      expenditures ranged from 7.64 to 18.15 MJ/day, but there was no difference (P =
      0.96) between the LE and LNE in energy expenditure during activity that was not
      designed to either improve or maintain fitness. These cross-sectional data on 49-
      to 70-yr-old women therefore suggest that 1) aerobic-type training results in a
      greater RMR per unit of body mass and also when statistical control is exerted
      for the effect of the metabolically active fat-free mass, 2) there is a large
      range in the energy intake necessary to maintain energy balance, and 3) aerobic
      training does not result in a compensatory reduction in energy expenditure during
      the remainder of the day.

PMID- 9516200
TI  - Age alters the cardiovascular response to direct passive heating.
AB  - During direct passive heating in young men, a dramatic increase in skin blood
      flow is achieved by a rise in cardiac output (Qc) and redistribution of flow from
      the splanchnic and renal vascular beds. To examine the effect of age on these
      responses, seven young (Y; 23 +/- 1 yr) and seven older (O; 70 +/- 3 yr) men were
      passively heated with water-perfused suits to their individual limit of thermal
      tolerance. Measurements included heart rate (HR), Qc (by acetylene rebreathing),
      central venous pressure (via peripherally inserted central catheter), blood
      pressures (by brachial auscultation), skin blood flow (from increases in forearm
      blood flow by venous occlusion plethysmography), splanchnic blood flow (by
      indocyanine green clearance), renal blood flow (by p-aminohippurate clearance),
      and esophageal and mean skin temperatures. Qc was significantly lower in the
      older than in the young men (11.1 +/- 0.7 and 7.4 +/- 0.2 l/min in Y and O,
      respectively, at the limit of thermal tolerance; P < 0. 05), despite similar
      increases in esophageal and mean skin temperatures and time to reach the limit of
      thermal tolerance. A lower stroke volume (99 +/- 7 and 68 +/- 4 ml/beat in Y and
      O, respectively, P < 0.05), most likely due to an attenuated increase in
      inotropic function during heating, was the primary factor for the lower Qc
      observed in the older men. Increases in HR were similar in the young and older
      men; however, when expressed as a percentage of maximal HR, the older men relied
      on a greater proportion of their chronotropic reserve to obtain the same HR
      response (62 +/- 3 and 75 +/- 4% maximal HR in Y and O, respectively, P < 0.05).
      Furthermore, the older men redistributed less blood flow from the combined
      splanchnic and renal circulations at the limit of thermal tolerance (960 +/- 80
      and 720 +/- 100 ml/min in Y and O, respectively, P < 0. 05). As a result of these
      combined attenuated responses, the older men had a significantly lower increase
      in total blood flow directed to the skin.

PMID- 9516202
TI  - Changes in agonist-antagonist EMG, muscle CSA, and force during strength training
      in middle-aged and older people.
AB  - Effects of 6 mo of heavy-resistance training combined with explosive exercises on
      neural activation of the agonist and antagonist leg extensors, muscle cross
      sectional area (CSA) of the quadriceps femoris, as well as maximal and explosive
      strength were examined in 10 middle-aged men (M40; 42 +/- 2 yr), 11 middle-aged
      women (W40; 39 +/- 3 yr), 11 elderly men (M70; 72 +/- 3 yr) and 10 elderly women
      (W70; 67 +/- 3 yr). Maximal and explosive strength remained unaltered during a 1
      mo control period with no strength training. After the 6 mo of training, maximal
      isometric and dynamic leg-extension strength increased by 36 +/- 4 and 22 +/- 2%
      (P < 0. 001) in M40, by 36 +/- 3 and 21 +/- 3% (P < 0.001) in M70, by 66 +/- 9
      and 34 +/- 4% (P < 0.001) in W40, and by 57 +/- 10 and 30 +/- 3% (P < 0.001) in
      W70, respectively. All groups showed large increases (P < 0.05-0.001) in the
      maximum integrated EMGs (iEMGs) of the agonist vastus lateralis and medialis.
      Significant (P < 0.05-0.001) increases occurred in the maximal rate of isometric
      force production and in a squat jump that were accompanied with increased (P <
      0.05-0. 01) iEMGs of the leg extensors. The iEMG of the antagonist biceps femoris
      muscle during the maximal isometric leg extension decreased in both M70 (from 24
      +/- 6 to 21 +/- 6%; P < 0.05) and in W70 (from 31 +/- 9 to 24 +/- 4%; P < 0.05)
      to the same level as recorded for M40 and W40. The CSA of the quadriceps femoris
      increased in M40 by 5% (P < 0.05), in W40 by 9% (P < 0.01), in W70 by 6% (P <
      0.05), and in M70 by 2% (not significant). Great training-induced gains in
      maximal and explosive strength in both middle-aged and elderly subjects were
      accompanied by large increases in the voluntary activation of the agonists, with
      significant reductions in the antagonist coactivation in the elderly subjects.
      Because the enlargements in the muscle CSAs in both middle-aged and elderly
      subjects were much smaller in magnitude, neural adaptations seem to play a
      greater role in explaining strength and power gains during the present strength
      training protocol.

PMID- 9516203
TI  - Improved oxygenation with prostaglandin F2alpha with and without inhaled nitric
      oxide in dogs.
AB  - Dogs of mixed breed (n = 7) were anesthetized, right lung atelectasis was
      established, and the cyclooxygenase pathway was blocked with ibuprofen.
      Measurements of pulmonary gas exchange were performed (fractional concentration
      of inspired O2 = 0.95) after infusions of prostaglandin F2alpha (PGF2alpha; 2
      microg . kg-1 . min-1), ventilation with nitric oxide (NO; 40 ppm), or both
      (PGF2alpha + NO) in random order. The arterial PO2 (PaO2) under control
      conditions was 117 +/- 16 Torr (shunt = 33 +/- 2.5%), was unchanged with NO alone
      (PaO2 = 114 +/- 17 Torr; shunt = 35.7 +/- 3. 1%), but was significantly improved
      with PGF2alpha alone (PaO2 = 180 +/- 28 Torr; shunt = 23.2 +/- 2.8%) and with the
      combination of PGF2alpha + NO (PaO2 = 202 +/- 30 Torr; shunt = 20.9 +/- 2.5%).
      The addition of NO did not significantly enhance the effectiveness of the
      PGF2alpha on PaO2. Simulation of these data in a computer model, combining
      pulmonary gas exchange and pulmonary blood flow, reproduced the results on the
      basis that vasoconstriction with PGF2alpha was maximal under hypoxia in the
      atelectatic lung and reduced by hyperoxia in the ventilated lung, consistent with
      the hypothesis of O2 dependence of PGF2alpha vasoconstriction.

PMID- 9516204
TI  - Myogenin, MyoD, and myosin expression after pharmacologically and surgically
      induced hypertrophy.
AB  - The relationship between myogenin or MyoD expression and hypertrophy of the rat
      soleus produced either by clenbuterol and 3,3', 5-triiodo-L-thyronine (CT)
      treatment or by surgical overload was examined. Mature female rats were subjected
      to surgical overload of the right soleus with the left soleus serving as a
      control. Another group received the same surgical treatment but were administered
      CT. Soleus muscles were harvested 4 wk after surgical overload and weighed.
      Myosin heavy chain isoforms were separated by using polyacrylamide gel
      electrophoresis while myogenin and MyoD expression were evaluated by Northern
      analysis. CT and functional overload increased soleus muscle weight. CT treatment
      induced the appearance of the fast type IIX myosin heavy chain isoform, depressed
      myogenin expression, and induced MyoD expression. However, functional overload
      did not alter myogenin or MyoD expression in CT-treated or non-CT-treated rats.
      Thus pharmacologically and surgically induced hypertrophy have differing effects
      on myogenin and MyoD expression, because their levels were associated with
      changes in myosin heavy chain composition (especially type IIX) rather than
      changes in muscle mass.

PMID- 9516206
TI  - Apnea and periodic breathing in bed-sharing and solitary sleeping infants.
AB  - Mother-infant bed sharing, compared with the solitary sleeping condition, has
      recently been associated with several physiological and behavioral effects.
      Because the physiological effects of bed sharing may also include respiratory
      changes, we compared the incidence of central and obstructive apneas and periodic
      breathing in bed-sharing and solitary sleeping infants. Twenty routinely bed
      sharing mother-infant pairs and fifteen routinely solitary sleeping pairs slept
      for 3 nights in a sleep laboratory. After an initial adaptation night, each pair
      spent 1 night bed sharing and 1 night in solitary sleep in random order. Apnea
      and periodic breathing were scored from polysomnographic recordings. The
      frequency of central apnea was significantly increased on the bed-sharing night,
      compared with the solitary night, regardless of routine sleeping arrangement.
      There were significantly fewer obstructive apneas on the bed-sharing night than
      on the solitary night, but only in routinely solitary sleeping infants. In both
      groups, there was a significantly higher frequency of periodic breathing events
      on the bed-sharing night than on the solitary night. These findings demonstrate
      that the bed-sharing environment can have a significant impact on respiratory
      control in the infant. Evidence is also presented to suggest that routine bed
      sharing may result in subtle neurophysiological and/or developmental differences
      in infants.

PMID- 9516205
TI  - Effects of short-term inactivity on glucose tolerance, energy expenditure, and
      blood flow in trained subjects.
AB  - The purpose of this investigation was to examine the effects of 7-10 days of
      inactivity (IA) on glucose tolerance (GT), resting metabolic rate (RMR), thermic
      effect of a meal (TEM), and limb blood flow in endurance-trained men. Eight
      highly trained (peak O2 consumption 64 +/- 2 ml . kg-1 . min-1) endurance
      athletes participated in this study involving two identical test days, one
      approximately 24 h after a normal training bout (Tr) and the second after 7-10
      days of IA. The following tests were conducted at each visit: 75-g oral glucose
      tolerance test (OGTT), RMR, and TEM and measurements of calf and forearm blood
      flow (BF) by using venous occlusive plethysmography. Body weight remained
      unchanged during this short period of IA (Tr, 78.5 +/- 1 kg; IA, 78.7 +/- 1 kg).
      The area under the glucose and insulin curves increased 65% (Tr, 3,375 +/- 877
      vs. IA, 5,559.4 +/- 621 mg . dl-1 . 180 min-1) and 73% (Tr, 2,182.5 +/- 270 vs.
      IA, 3,793.1 +/- 739 microU . ml-1 . 180 min-1) after IA, respectively (P < 0.01).
      RMR decreased significantly (4%; 1.5 +/- 0. 02 vs. 1.44 +/- 0.02 kcal/min; P <
      0.05) and respiratory exchange ratio during the OGTT increased (4%, 0.812 +/-
      0.011 vs. 0.842 +/- 0. 009; P < 0.05) after IA, whereas TEM increased similarly
      in the Tr and IA states. In the Tr state, mean calf BF increased by 22% (3.17 +/-
      0.22 vs. 3.87 +/- 0.38 ml . 100 ml-1 . min-1; P < 0.05) during the OGTT but
      remained unchanged after IA, whereas no differences at rest or during OGTTs
      existed between the two conditions for forearm BF. Incremental insulin area above
      fasting during the OGTT was correlated with mean calf BF in the Tr (r = 0.76, P <
      0.05) and IA (r = 0.72, P < 0.05) states. In conclusion, 7-10 days of IA results
      in a deterioration in GT and a reduction in RMR. After glucose ingestion, calf BF
      was elevated compared with resting levels in the Tr state but was unchanged in
      the IA state; however, limb BF was not related to GT or RMR. Thus our findings
      raise questions regarding the relative contribution of BF in modulating glucose
      tolerance and energy expenditure in endurance athletes in their habitual Tr or IA
      state.

PMID- 9516207
TI  - Optical measurement of isolated canine lung filtration coefficients after alloxan
      infusion.
AB  - In this study, lung filtration coefficient (Kfc) was measured in eight isolated
      canine lung preparations by using three methods: standard gravimetric (Std),
      blood-corrected gravimetric (BC), and optical. The lungs were held in zone III
      conditions and were subjected to an average venous pressure increase of 8.79 +/-
      0.93 (mean +/- SD) cmH2O. The permeability of the lungs was increased with an
      infusion of alloxan (75 mg/kg). The resulting Kfc values (in milliliters . min-1
      . cmH2O-1 . 100 g dry lung weight-1) measured by using Std and BC gravimetric
      techniques before vs. after alloxan infusion were statistically different: Std,
      0.527 +/- 0.290 vs. 1. 966 +/- 0.283; BC, 0.313 +/- 0.290 vs. 1.384 +/- 0.290.
      However, the optical technique did not show any statistical difference between
      pre- and postinjury with alloxan, 0.280 +/- 0.305 vs. 0.483 +/- 0. 297,
      respectively. The alloxan injury, quantified by using multiple-indicator
      techniques, showed an increase in permeability and a corresponding decrease in
      reflection coefficient for albumin (sigmaf). Because the optical method measures
      the product of Kfc and sigmaf, this study shows that albumin should not be used
      as an intravascular optical filtration marker when permeability is elevated.
      However, the optical technique, along with another means of measuring Kfc (such
      as BC), can be used to calculate the sigmaf of a tracer (in this study, sigmaf of
      0.894 at baseline and 0.348 after injury). Another important finding of this
      study was that the ratio of baseline-to-injury Kfc values was not statistically
      different for Std and BC techniques, indicating that the percent contribution of
      slow blood-volume increases does not change because of injury.

PMID- 9516208
TI  - Effect on airway caliber of stimulation of the hypothalamic locomotor region.
AB  - Airway dilation is one of the many autonomic responses to exercise. Two neural
      mechanisms are believed to evoke these responses: central command and the muscle
      reflex. Previously, we found that activation of central command, evoked by
      electrical and chemical stimulation of the mesencephalic locomotor region,
      constricted the airways rather than dilated them. In the present study we
      examined in decerebrate paralyzed cats the role played by the hypothalamic
      locomotor region, the activation of which also evokes central command, in causing
      the airway dilator response to exercise. We found that activation of the
      hypothalamic locomotor region by electrical and chemical stimuli evoked fictive
      locomotion and, for the most part, airway constriction. Fictive locomotion also
      occurred spontaneously, and this too, for the most part, was accompanied by
      airway constriction. We conclude that central command plays a minor role in the
      airway dilator response to exercise.

PMID- 9516209
TI  - Role of extracellular [Ca2+] in fatigue of isolated mammalian skeletal muscle.
AB  - The possible role of altered extracellular Ca2+ concentration ([Ca2+]o) in
      skeletal muscle fatigue was tested on isolated slow-twitch soleus and fast-twitch
      extensor digitorum longus muscles of the mouse. The following findings were made.
      1) A change from the control solution (1.3 mM [Ca2+]o) to 10 mM [Ca2+]o, or to
      nominally Ca2+-free solutions, had little effect on tetanic force in nonfatigued
      muscle. 2) Almost complete restoration of tetanic force was induced by 10 mM
      [Ca2+]o in severely K+-depressed muscle (extracellular K+ concentration of 10-12
      mM). This effect was attributed to a 5-mV reversal of the K+-induced
      depolarization and subsequent restoration of ability to generate action
      potentials (inferred by using the twitch force-stimulation strength
      relationship). 3) Tetanic force depressed by lowered extracellular Na+
      concentration (40 mM) was further reduced with 10 mM [Ca2+]o. 4) Tetanic force
      loss at elevated extracellular K+ concentration (8 mM) and lowered extracellular
      Na+ concentration (100 mM) was partially reversed with 10 mM [Ca2+]o or markedly
      exacerbated with low [Ca2+]o. 5) Fatigue induced by using repeated tetani in
      soleus was attenuated at 10 mM [Ca2+]o (due to increased resting and evoked
      forces) and exacerbated at low [Ca2+]o. These combined results suggest, first,
      that raised [Ca2+]o protects against fatigue rather than inducing it and, second,
      that a considerable depletion of [Ca2+]o in the transverse tubules may contribute
      to fatigue.

PMID- 9516211
TI  - Effect of increased blood glucose availability on glucose kinetics during
      exercise.
AB  - This study examined the effect of increased blood glucose availability on glucose
      kinetics during exercise. Five trained men cycled for 40 min at 77 +/- 1% peak
      oxygen uptake on two occasions. During the second trial (Glu), glucose was
      infused at a rate equal to the average hepatic glucose production (HGP) measured
      during exercise in the control trial (Con). Glucose kinetics were measured by a
      primed continuous infusion of D-[3-3H]glucose. Plasma glucose increased during
      exercise in both trials and was significantly higher in Glu. HGP was similar at
      rest (Con, 11.4 +/- 1.2; Glu, 10.6 +/- 0.6 micromol . kg-1 . min-1). After 40 min
      of exercise, HGP reached a peak of 40.2 +/- 5.5 micromol . kg-1 . min-1 in Con;
      however, in Glu, there was complete inhibition of the increase in HGP during
      exercise that never rose above the preexercise level. The rate of glucose
      disappearance was greater (P < 0.05) during the last 15 min of exercise in Glu.
      These results indicate that an increase in glucose availability inhibits the rise
      in HGP during exercise, suggesting that metabolic feedback signals can override
      feed-forward activation of HGP during strenuous exercise.

PMID- 9516210
TI  - Maintenance of myonuclear domain size in rat soleus after overload and growth
      hormone/IGF-I treatment.
AB  - The purpose of this study was to determine the effects of functional overload
      (FO) combined with growth hormone/insulin-like growth factor I (GH/IGF-I)
      administration on myonuclear number and domain size in rat soleus muscle fibers.
      Adult female rats underwent bilateral ablation of the plantaris and gastrocnemius
      muscles and, after 7 days of recovery, were injected three times daily for 14
      days with GH/IGF-I (1 mg/kg each; FO + GH/IGF-I group) or saline vehicle (FO
      group). Intact rats receiving saline vehicle served as controls (Con group).
      Muscle wet weight was 32% greater in the FO than in the Con group: 162 +/- 8 vs.
      123 +/- 16 mg. Muscle weight in the FO + GH/IGF-I group (196 +/- 14 mg) was 59
      and 21% larger than in the Con and FO groups, respectively. Mean soleus fiber
      cross-sectional area of the FO + GH/IGF-I group (2,826 +/- 445 microm2) was
      increased compared with the Con (2,044 +/- 108 microm2) and FO (2,267 +/- 301
      microm2) groups. The difference in fiber size between the FO and Con groups was
      not significant. Mean myonuclear number increased in FO (187 +/- 15 myonuclei/mm)
      and FO + GH/IGF-I (217 +/- 23 myonuclei/mm) rats compared with Con (155 +/- 12
      myonuclei/mm) rats, although the difference between FO and FO + GH/IGF-I animals
      was not significant. The mean cytoplasmic volume per myonucleus (myonuclear
      domain) was similar across groups. These results demonstrate that the larger mean
      muscle weight and fiber cross-sectional area occurred when FO was combined with
      GH/IGF-I administration and that myonuclear number increased concomitantly with
      fiber volume. Thus there appears to be some mechanism(s) that maintains the
      myonuclear domain when a fiber hypertrophies.

PMID- 9516212
TI  - Free mobilization and low- to high-intensity exercise in immobilization-induced
      muscle atrophy.
AB  - After 3 wk of immobilization, the effects of free cage activity and low- and high
      intensity treadmill running (8 wk) on the morphology and histochemistry of the
      soleus and gastrocnemius muscles in male Sprague-Dawley rats were investigated.
      In both muscles, immobilization produced a significant (P < 0.001) increase in
      the mean percent area of intramuscular connective tissue (soleus: 18.9% in
      immobilized left hindlimb vs. 3.6% in nonimmobilized right hindlimb) and in the
      relative number of muscle fibers with pathological alterations (soleus: 66% in
      immobilized hindlimb vs. 6% in control), with a simultaneous significant (P <
      0.001) decrease in the intramuscular capillary density (soleus: mean capillary
      density in the immobilized hindlimb only 63% of that in the nonimmobilized
      hindlimb) and muscle fiber size (soleus type I fibers: mean fiber size in the
      immobilized hindlimb only 69% of that in the nonimmobilized hindlimb). Many of
      these changes could not be corrected by free remobilization, whereas low- and
      high-intensity treadmill running clearly restored the changes toward control
      levels, the effect being most complete in the high-intensity running group.
      Collectively, these findings indicate that immobilization-induced pathological
      structural and histochemical alterations in rat calf muscles are, to a great
      extent, reversible phenomena if remobilization is intensified by physical
      training. In this respect, high-intensity exercise seems more beneficial than low
      intensity exercise.

PMID- 9516213
TI  - Skeletal muscle afferent regulation of bioassayable growth hormone in the rat
      pituitary.
AB  - There are forms of growth hormone (GH) in the plasma and pituitary of the rat and
      in the plasma of humans that are undetected by presently available immunoassays
      (iGH) but can be measured by bioassay (bGH). Although the regulation of iGH
      release is well documented, the mechanism(s) of bGH release is unclear. On the
      basis of changes in bGH and iGH secretion in rats that had been exposed to
      microgravity conditions, we hypothesized that neural afferents play a role in
      regulating the release of these hormones. To examine whether bGH secretion can be
      modulated by afferent input from skeletal muscle, the proximal or distal ends of
      severed hindlimb fast muscle nerves were stimulated ( approximately 2 times
      threshold) in anesthetized rats. Plasma bGH increased approximately 250%, and
      pituitary bGH decreased approximately 60% after proximal nerve trunk stimulation.
      The bGH response was independent of muscle mass or whether the muscles were
      flexors or extensors. Distal nerve stimulation had little or no effect on plasma
      or pituitary bGH. Plasma iGH concentrations were unchanged after proximal nerve
      stimulation. Although there may be multiple regulatory mechanisms of bGH, the
      present results demonstrate that the activation of low-threshold afferents from
      fast skeletal muscles can play a regulatory role in the release of bGH, but not
      iGH, from the pituitary in anesthetized rats.

PMID- 9516214
TI  - Grain sorghum dust increases macromolecular efflux from the in situ nasal mucosa.
AB  - The purpose of this study was to determine whether an aqueous extract of grain
      sorghum dust increases macromolecular efflux from the nasal mucosa in vivo and,
      if so, whether this response is mediated, in part, by substance P. Suffusion of
      grain sorghum dust extract on the in situ nasal mucosa of anesthetized hamsters
      elicits a significant increase in clearance of fluorescein isothiocyanate-labeled
      dextran (FITC-dextran; mol mass, 70 kDa; P < 0.05). This response is
      significantly attenuated by CP-96345 and RP-67580, two selective, but
      structurally distinct, nonpeptide neurokinin 1 (substance P)-receptor
      antagonists, but not by CP-96344, the 2R,3R enantiomer of CP-96345 (P < 0.05). CP
      96345 has no significant effects on adenosine-induced increase in clearance of
      FITC-dextran from the in situ nasal mucosa. CP-96345 and RP-67580, but not CP
      96344, significantly attenuate substance P-induced increases in clearance of FITC
      dextran from the in situ nasal mucosa (P < 0.05). Collectively, these data
      suggest that grain sorghum dust elicits neurogenic plasma exudation from the in
      situ nasal mucosa.

PMID- 9516215
TI  - The Hering-Breuer reflex in anesthetized infants: end-inspiratory vs. end
      expiratory occlusion technique.
AB  - Both end-inspiratory (EIO) and end-expiratory (EEO) occlusions have been used to
      measure the strength of the Hering-Breuer inflation reflex (HBIR) in infants. The
      purpose of this study was to compare both techniques in anesthetized infants. In
      each infant, HBIR activity was calculated as the relative prolongation of
      expiratory and inspiratory time during EIO and EEO, respectively. Respiratory
      drive was assessed from the change in airway pressure during inspiratory effort
      against the occlusion, both at a fixed time interval of 100 ms (P0.1) and a fixed
      proportion (10%) of the occluded inspiratory time (P10%). Twenty-two infants [age
      14.3 +/- 6. 4 (SD) mo] were studied. No HBIR activity was present during EIO [
      11.8 +/- 15.9 (SD) %]. By contrast, there was significant, albeit weak, reflex
      activity during EEO [HBIR: 27.2 +/- 17.4%]. A strong HBIR (up to 310%) was
      elicited in six of seven infants in whom EIO was repeated after lung inflation.
      P0.1 was similar during both types of occlusions, whereas mean +/- SD P10% was
      lower during EEO than during EIO: 0.198 +/- 0.09 vs. 0.367 +/- 0.15 kPa,
      respectively (P < 0.01). These data suggest a difference in the central
      integration of stretch receptor activity in infants during anesthesia compared
      with during sleep.

PMID- 9516216
TI  - Airway mechanics, gas exchange, and blood flow in a nonlinear model of the normal
      human lung.
AB  - A model integrating airway/lung mechanics, pulmonary blood flow, and gas exchange
      for a normal human subject executing the forced vital capacity (FVC) maneuver is
      presented. It requires as input the intrapleural pressure measured during the
      maneuver. Selected model-generated output variables are compared against measured
      data (flow at the mouth, change in lung volume, and expired O2 and CO2
      concentrations at the mouth). A nonlinear parameter-estimation algorithm is
      employed to vary selected sensitive model parameters to obtain reasonable least
      squares fits to the data. This study indicates that 1) all three components of
      the respiratory model are necessary to characterize the FVC maneuver; 2) changes
      in pulmonary blood flow rate are associated with changes in alveolar and
      intrapleural pressures and affect gas exchange and the time course of expired gas
      concentrations; and 3) a collapsible midairway segment must be included to match
      airflow during a forced expiration. Model simulations suggest that the
      resistances to airflow offered by the collapsible segment and the small airways
      are significant throughout forced expiration; their combined effect is needed to
      adequately match the inspiratory and expiratory flow-volume loops. Despite the
      limitations of this lumped single-compartment model, a remarkable agreement with
      airflow and expired gas concentration measurements is obtained for normal
      subjects. Furthermore, the model provides insight into the important dynamic
      interactions between ventilation and perfusion during the FVC maneuver.

PMID- 9516217
TI  - Prolonged exposure to halothane and associated changes in carbohydrate metabolism
      in rat muscles in vivo.
AB  - Halothane, an anesthetic presently used in animal experimentation, is reported to
      stimulate glycogen breakdown in isolated preparations of rat skeletal muscles,
      suggesting that it may not be a suitable anesthetic for the study of glycogen
      metabolism in rats in vivo. The purpose of this study was to establish whether
      prolonged exposure to halothane in rats in vivo is associated with accelerated
      glycogenolysis. Exposure of rats to halothane for up to 1 h was not accompanied
      by either any change in the levels of glycogen or increase in activity ratios of
      glycogen phosphorylase in muscles, irrespective of their fiber compositions. In
      marked contrast, the levels of lactate, inorganic phosphate, glucose 1-phosphate,
      glucose 6-phosphate, fructose 1,6-bisphosphate, and fructose 2, 6-bisphosphate
      changed progressively during anesthesia. Accordingly, the interpretation of
      muscle metabolite levels must be performed with caution in experiments involving
      prolonged exposure to halothane. Overall, our findings indicate that the reported
      halothane-mediated stimulation of glycogen breakdown in vitro is likely to be an
      artifact and that halothane is a suitable anesthetic for experiments concerned
      with glycogen metabolism in rats.

PMID- 9516218
TI  - Body composition by air-displacement plethysmography by using predicted and
      measured thoracic gas volumes.
AB  - The BOD POD, a new air-displacement plethysmograph for measuring human body
      composition, utilizes the inverse relationship between pressure and volume
      (Boyle's law) to measure body volume directly. The quantity of air in the lungs
      during tidal breathing, the average thoracic gas volume (Vtg), is also measured
      by the BOD POD by using a standard plethysmographic technique. Alternatively, the
      BOD POD provides the use of a predicted Vtg (Vtgpred). The validity of using
      Vtgpred in place of measured Vtg (Vtgmeas) to determine the percentage of body
      fat (%BF) was evaluated in 50 subjects (36 women, 14 men; ages 18-56 yr). There
      was no significant difference between Vtgmeas and Vtgpred (mean difference +/-
      SE, 53.5 +/- 63.3 ml) nor in %BF by using Vtgmeas vs. Vtgpred (0.2 +/- 0.2 %BF).
      On an individual basis, %BF measured by using Vtgmeas vs. Vtgpred differed within
      +/-2.0% BF for 82% of the subjects; maximum differences were -2.9 to +3.0% BF.
      For comparison, data from 24 subjects who had undergone hydrostatic weighing were
      evaluated for the validity of using predicted vs. measured residual lung volume
      (VRpred vs. VRmeas, respectively). Differences between VRmeas and VRpred and in
      %BF calculated by using VRmeas vs. VRpred were significant (187 +/- 46 ml and 1.4
      +/- 0.3% BF, respectively; P < 0.001). On an individual basis, %BF determined by
      using VRmeas vs. VRpred differed within +/-2.0% BF for 46% of the subjects;
      maximum differences were -2.9 to +3.8% BF. With respect to %BF measured by air
      displacement, our findings support the use of Vtgpred for group mean comparisons
      and for purposes such as screening in young to middle-aged individuals. This
      contrasts with the use of VRpred in hydrostatic weighing, which leads to
      significant errors in the estimation of %BF. Furthermore, although the use of
      Vtgpred has some application, determining Vtgmeas is relatively simple in most
      cases. Therefore, we recommend that the use of Vtgmeas remain as standard
      experimental and clinical practice.

PMID- 9516219
TI  - Declining morbidity and mortality among patients with advanced human
      immunodeficiency virus infection. HIV Outpatient Study Investigators.
AB  - BACKGROUND AND METHODS: National surveillance data show recent, marked reductions
      in morbidity and mortality associated with the acquired immunodeficiency syndrome
      (AIDS). To evaluate these declines, we analyzed data on 1255 patients, each of
      whom had at least one CD4+ count below 100 cells per cubic millimeter, who were
      seen at nine clinics specializing in the treatment of human immunodeficiency
      virus (HIV) infection in eight U.S. cities from January 1994 through June 1997.
      RESULTS: Mortality among the patients declined from 29.4 per 100 person-years in
      the first quarter of 1995 to 8.8 per 100 in the second quarter of 1997. There
      were reductions in mortality regardless of sex, race, age, and risk factors for
      transmission of HIV. The incidence of any of three major opportunistic infections
      (Pneumocystis carinii pneumonia, Mycobacterium avium complex disease, and
      cytomegalovirus retinitis) declined from 21.9 per 100 person-years in 1994 to 3.7
      per 100 person-years by mid-1997. In a failure-rate model, increases in the
      intensity of antiretroviral therapy (classified as none, monotherapy, combination
      therapy without a protease inhibitor, and combination therapy with a protease
      inhibitor) were associated with stepwise reductions in morbidity and mortality.
      Combination antiretroviral therapy was associated with the most benefit; the
      inclusion of protease inhibitors in such regimens conferred additional benefit.
      Patients with private insurance were more often prescribed protease inhibitors
      and had lower mortality rates than those insured by Medicare or Medicaid.
      CONCLUSIONS: The recent declines in morbidity and mortality due to AIDS are
      attributable to the use of more intensive antiretroviral therapies.

PMID- 9516220
TI  - Effect of troglitazone in insulin-treated patients with type II diabetes
      mellitus. Troglitazone and Exogenous Insulin Study Group.
AB  - BACKGROUND: Troglitazone is a new oral antidiabetic drug that increases the
      sensitivity of peripheral tissues to insulin. It may therefore increase the
      efficacy of exogenous insulin in patients with insulin-resistant diabetes
      mellitus. METHODS: We studied the effect of troglitazone or placebo in 350
      patients with poorly controlled non-insulin-dependent (type 2) diabetes mellitus
      (glycosylated hemoglobin values, 8 to 12 percent; normal, 4.3 to 6.1 percent)
      despite therapy with at least 30 U of insulin daily. The patients were randomly
      assigned to receive 200 mg of troglitazone (116 patients), 600 mg of troglitazone
      (116 patients), or placebo (118 patients) daily for 26 weeks. Insulin doses were
      not increased and were reduced only to prevent hypoglycemia. Glycosylated
      hemoglobin, serum glucose while fasting, serum total cholesterol, high-density
      lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides
      were measured 5 times during an 8-week base-line period and 10 times during the
      26-week treatment period. Daily insulin doses were recorded during both periods.
      RESULTS: Ninety percent of the patients completed the study. The adjusted mean
      glycosylated hemoglobin values decreased by 0.8 and 1.4 percentage points,
      respectively, in the group given 200 mg of troglitazone and the group given 600
      mg of troglitazone, and fasting serum glucose concentrations decreased by 35 and
      49 mg per deciliter (1.9 and 2.7 mmol per liter), respectively, despite decreases
      in the insulin dose of 11 percent and 29 percent (P<0.001 for all comparisons
      with the placebo group). Serum total cholesterol, low-density lipoprotein
      cholesterol, and high-density lipoprotein cholesterol concentrations increased
      slightly and serum triglyceride concentrations decreased slightly in the
      troglitazone-treated patients. CONCLUSIONS: When given in conjunction with
      insulin, troglitazone improves glycemic control in patients with type 2 diabetes
      mellitus.

PMID- 9516221
TI  - Efficacy and metabolic effects of metformin and troglitazone in type II diabetes
      mellitus.
AB  - BACKGROUND: Combination therapy is logical for patients with non-insulin
      dependent (type 2) diabetes mellitus, because they often have poor responses to
      single-drug therapy. We studied the efficacy and physiologic effects of metformin
      and troglitazone alone and in combination in patients with type 2 diabetes.
      METHODS: We randomly assigned 29 patients to receive either metformin or
      troglitazone for three months, after which they were given both drugs for another
      three months. Plasma glucose concentrations during fasting and postprandially and
      glycosylated hemoglobin values were measured periodically during both treatments.
      Endogenous glucose production and peripheral glucose disposal were measured at
      base line and after three and six months. RESULTS: During metformin therapy,
      fasting and postprandial plasma glucose concentrations decreased by 20 percent
      (58 mg per deciliter [3.2 mmol per liter], P<0.001) and 25 percent (87 mg per
      deciliter [4.8 mmol per liter], P<0.001), respectively. The corresponding
      decreases during troglitazone therapy were 20 percent (54 mg per deciliter [2.9
      mmol per liter], P=0.01) and 25 percent (83 mg per deciliter [4.6 mmol per
      liter], P<0.001). Endogenous glucose production decreased during metformin
      therapy by a mean of 19 percent (P=0.001), whereas it was unchanged by
      troglitazone therapy (P=0.04 for the comparison between groups). The mean rate of
      glucose disposal increased by 54 percent during troglitazone therapy (P=0.006)
      and 13 percent during metformin therapy (P= 0.03 for the comparison within the
      group and between groups). In combination, metformin and troglitazone further
      lowered fasting and postprandial plasma glucose concentrations by 18 percent (41
      mg per deciliter [2.3 mmol per liter], P=0.001) and 21 percent (54 mg per
      deciliter [3.0 mmol per liter], P<0.001), respectively, and the mean glycosylated
      hemoglobin value decreased 1.2 percentage points. CONCLUSIONS: Metformin and
      troglitazone have equal and additive beneficial effects on glycemic control in
      patients with type 2 diabetes. Metformin acts primarily by decreasing endogenous
      glucose production, and troglitazone by increasing the rate of peripheral glucose
      disposal.

PMID- 9516223
TI  - CDKN2A mutations in multiple primary melanomas.
AB  - BACKGROUND: Germ-line mutations in the CDKN2A tumor-suppressor gene (also known
      as p16, p16INK4a, and MTS1) have been linked to the development of melanoma in
      some families with inherited melanoma. Whether mutations in CDKN2A confer a
      predisposition to sporadic (nonfamilial) melanoma is not known. In some patients
      with sporadic melanoma, one or more additional primary lesions develop,
      suggesting that some of these patients have an underlying genetic susceptibility
      to the cancer. We hypothesized that this predisposition might be due to germ-line
      CDKN2A mutations. METHODS: We used the polymerase chain reaction, single-strand
      conformation polymorphism analysis, and direct DNA sequencing to identify germ
      line mutations in the CDKN2A gene in patients with multiple primary melanomas who
      did not have family histories of the disease. A quantitative yeast two-hybrid
      assay was used to evaluate the functional importance of the CDKN2A variants.
      RESULTS: Of 33 patients with multiple primary melanomas, 5 (15 percent; 95
      percent confidence interval, 4 percent to 27 percent) had germ-line CDKN2A
      mutations. These included a 24-bp insertion at the 5' end of the coding sequence,
      three missense mutations (Arg24Pro, Met53Ile, and Ser56Ile), and a 2-bp deletion
      at position 307 to 308 (resulting in a truncated CDKN2A protein). In three
      families, CDKN2A mutations identical to those in the probands were found in other
      family members. In two families with mutations, we uncovered previously unknown
      evidence of family histories of melanoma. CONCLUSIONS: Some patients with
      multiple primary melanomas but without family histories of the disease have germ
      line mutations of the CDKN2A gene. The presence of multiple primary melanomas may
      signal a genetic susceptibility to melanoma not only in the index patient but
      also in family members, who may benefit from melanoma-surveillance programs.

PMID- 9516224
TI  - Images in clinical medicine. Molluscum contagiosum in a patient with the acquired
      immunodeficiency syndrome.

PMID- 9516222
TI  - Liver failure and death after exposure to microcystins at a hemodialysis center
      in Brazil.
AB  - BACKGROUND: Hemodialysis is a common but potentially hazardous procedure. From
      February 17 to 20, 1996, 116 of 130 patients (89 percent) at a dialysis center
      (dialysis center A) in Caruaru, Brazil, had visual disturbances, nausea, and
      vomiting associated with hemodialysis. By March 24, 26 of the patients had died
      of acute liver failure. METHODS: A case patient was defined as any patient
      undergoing dialysis at dialysis center A or Caruaru's other dialysis center
      (dialysis center B) during February 1996 who had acute liver failure. To
      determine the risk factors for and the source of the outbreak, we conducted a
      cohort study of the 130 patients at dialysis center A and the 47 patients at
      dialysis center B, reviewed the centers' water supplies, and collected water,
      patients' serum, and postmortem liver tissue for microcystin assays. RESULTS: One
      hundred one patients (all at dialysis center A) met the case definition, and 50
      died. Affected patients who died were older than those who survived (median age,
      47 vs. 35 years, P<0.001). Furthermore, all 17 patients undergoing dialysis on
      the Tuesday-, Thursday-, and Saturday-night schedule became ill, and 13 of them
      (76 percent) died. Both centers received water from a nearby reservoir. However,
      the water supplied to dialysis center B was treated, filtered, and chlorinated,
      whereas the water supplied to dialysis center A was not. Microcystins produced by
      cyanobacteria were detected in water from the reservoir and from dialysis center
      A and in serum and liver tissue of case patients. CONCLUSIONS: Water used for
      hemodialysis can contain toxic materials, and its quality should therefore be
      carefully monitored.

PMID- 9516225
TI  - Imaging the brain. Second of two parts.

PMID- 9516227
TI  - Should human cloning research be off limits?

PMID- 9516228
TI  - Progress and problems in the fight against AIDS.

PMID- 9516229
TI  - A novel antidiabetic drug, troglitazone--reason for hope and concern.

PMID- 9516230
TI  - The CDKN2A tumor-suppressor locus--a tale of two proteins.

PMID- 9516231
TI  - Truth or consequences.

PMID- 9516232
TI  - The role of anionic lipids in protein insertion and translocation in bacterial
      membranes.

PMID- 9516233
TI  - Large conductance Ca(2+)-activated K+ channels in the soma of rat motoneurones.
AB  - Properties of large conductance Ca(2+)-activated K+ channels were studied in the
      soma of motoneurones visually identified in thin slices of neonatal rat spinal
      cord. The channels had a conductance of 82 +/- 5 pS in external Ringer solution
      (5.6 mM Ko+/(/)155 mM Ki+) and 231 +/- 4 pS in external high-Ko solution (155 mM
      Ko+/(/)155 mM Ki+). The channels were activated by depolarization and by an
      increase in internal Ca2+ concentration. Potentials of half-maximum channel
      activation (E50) were -13, -34, -64 and -85 mV in the presence of 10(-6), 10(-5),
      10(-4) and 10(-3) M internal Ca2+, respectively. Using an internal solution
      containing 10(-4) M Ca2+, averaged KCa currents showed fast activation within 2-3
      msec after a voltage step to +50 mV. Averaged KCa currents did not inactivate
      during 400 msec voltage pulses. External TEA reduced the apparent single-channel
      amplitude with a 50% blocking concentration (IC50) of 0.17 +/- 0.02 mM. KCa
      channels were completely suppressed by externally applied 100 mM charybdotoxin.
      It is concluded that KCa channels activated by Ca2+ entry during the action
      potential play an important role in the excitability of motoneurones.

PMID- 9516234
TI  - Villus and crypt cell composition in the secreting mouse jejunum measured with x
      ray microanalysis.
AB  - The response of the villus and crypt cells of the mouse jejunum to secretagogues
      has been assessed through measurements of cellular composition with x-ray
      microanalysis. In nonstimulated tissues the Na concentration ([Na]c) of the crypt
      cells was significantly less, and the K ([K]c) and Cl ([Cl]c) concentrations were
      significantly greater, than that of the villus cells. There was also a decreasing
      gradient of [Na]c and increasing gradient of [K]c from the villus tip to crypt
      base due to a greater number of cells with a high [Na]c and low [K]c in the upper
      regions of the villi. Theophylline (10 mmol L-1) stimulated a sustained increase
      in bumetanide sensitive short circuit current (Isc) and significantly decreased
      the [Na]c of the villus cells. Similar, but smaller changes were seen in the
      crypt cells. Changes in villus cell [Na]c reflected a reduction in the number of
      cells with a high [Na]c. Inhibition of the apical Na/H exchanger (1 mmol L-1
      amiloride) had little effect on basal Isc and the subsequent addition of
      theophylline increased Isc to a comparable extent as seen without amiloride.
      However, after amiloride treatment the only change in cellular composition was a
      reduction in the [Cl]c of both crypt and villus cells, suggesting that both
      regions are involved in the secretory response. These data suggest that the
      dominant response of the jejunum to secretagogues is an inhibition of Na
      absorption via Na/H exchange in the villi and the secretory response is
      distributed throughout the crypt/villus axis.

PMID- 9516236
TI  - Activation by angiotensin II of Ca(2+)-dependent K+ and Cl- currents in zona
      fasciculata cells of bovine adrenal gland.
AB  - The effects of angiotensin II (100 nM) on the electrical membrane properties of
      zona fasciculata cells isolated from calf adrenal gland were studied using the
      whole cell patch recording method. In current-clamp condition, angiotension II
      induced a biphasic membrane response which began by a transient hyperpolarization
      followed by a depolarization more positive than the control resting potential.
      These effects were abolished by Losartan (10(-5) M), an antagonist of angiotensin
      receptors of type 1. The angiotensin II-induced transient hyperpolarization was
      characterized in voltage-clamp condition from a holding potential of -10 mV.
      Using either the perforated or the standard recording method, a transient outward
      current accompanied by an increase of the membrane conductance was observed in
      response to the hormonal stimulation. This outward current consisted of an
      initial fast peak followed by an oscillating or a slowly decaying plateau
      current. In Cl(-)-free solution, the outward current reversed at -78.5 mV, a
      value close to EK. It was blocked by external TEA (20 mM) and by apamin (50 nM).
      In K(+)-free solution, the transient outward current, sensitive to Cl- channel
      blocker DPC (400 microM), reversed at -52 mV, a more positive potential than ECl.
      Its magnitude changed in the same direction as the driving force for Cl-. The
      hormone-induced transient outward current was never observed when EGTA (5 mM) was
      added to the pipette solution. The plateau current was suppressed in nominally
      CA(2+)-free solution (47% of cells) and was reversibly blocked by Cd2+ (300
      microM) but not by nisoldipine (0.5-1 microM) which inhibited voltage-gated Ca2+
      currents identified in this cell type. The present experiments show that the
      transient hyperpolarization induced by angiotensin II is due to Ca(2+)-dependent
      K+ and Cl- currents. These two membrane currents are co-activated in response to
      an internal increase of [Ca2+]i originating from intra- and extracellular stores.

PMID- 9516235
TI  - Cytoplasmic pH responses to carbonic anhydrase inhibitors in cultured rabbit
      nonpigmented ciliary epithelium.
AB  - Carbonic anhydrase (CA) inhibitors lower the rate of aqueous humor (AH) secretion
      into the eye. Different CA isozymes might play different roles in the response.
      Here we have studied the effects of carbonic anhydrase inhibitors on cytoplasmic
      pH (pHi) regulation, using a dextran-bound CA inhibitor (DBI) to selectively
      inhibit membrane-associated CA in a cell line derived from rabbit NPE. pHi was
      measured using the fluorescent dye BCECF and the pHi responses to the cell
      permeable CA inhibitor acetazolamide (ACTZ) and DBI were compared. ACTZ markedly
      inhibited the rapid pHi changes elicited by bicarbonate/CO2 removal and
      readdition but DBI was ineffective in this respect, consistent with the inability
      of DBI to enter the cell and inhibit cytoplasmic CA isozymes. Added alone, ACTZ
      and DBI caused a similar reduction (0.2 pH units) of baseline pHi. We considered
      whether CA-IV might facilitate H+ extrusion via Na-H exchange. The Na-H exchanger
      inhibitor amiloride (1 mM) reduced pHi 0.52 +/- 0.10 pH units. In the presence of
      DBI, the magnitude of pHi reduction caused by amiloride was significantly (P <
      0.05) reduced to 0.26 +/- 0.09 pH units. ACTZ similarly reduced the magnitude of
      the pHi reduction. DBI also reduced by approximately 40% the rate of pHi recovery
      in cells acidified by an ammonium chloride (20 mM) prepulse; a reduction in pHi
      recovery rate was also caused by ACTZ and amiloride. DBI failed to alter the pHi
      alkalinization response caused by elevating external potassium concentration, a
      response insensitive to amiloride but sensitive to ACTZ. These observations are
      consistent with a reduction in Na-H exchanger activity in the presence of DBI or
      ACTZ. We suggest that the CA-IV isozyme might catalyze rapid equilibration of H+
      and HCO3- with CO2 in the unstirred layer outside the plasma membrane, preventing
      local accumulation of H+ which competes with sodium for the same external Na-H
      exchanger binding site. Inhibition of CA-IV could produce pHi changes that might
      alter the function of other ion transporters and channels in the NPE.

PMID- 9516237
TI  - Purification and characterization of a novel chemorepellent receptor from
      Tetrahymena thermophila.
AB  - Chemosensory transduction and adaptation are important aspects of signal
      transduction mechanisms in many cell types, ranging from prokaryotes to
      differentiated tissues such as neurons. The eukaryotic ciliated protozoan,
      Tetrahymena thermophila, is capable of responding to both chemoattractants
      (O'Neill et al., 1985; Leick, 1992; Kohidai, Karsa & Csaba, 1994, 1995) and
      chemorepellents (Francis & Hennessey, 1995; Kuruvilla, Kim & Hennessey, 1997). An
      example of a nontoxic, depolarizing chemorepellent in Tetrahymena is
      extracellular lysozyme (Francis & Hennessey, 1995; Hennessey, Kim & Satir, 1995).
      Lysozyme is an effective chemorepellent at micromolar concentrations, binds to a
      single class of externally facing membrane receptors and prolonged exposure (10
      min) produces specific chemosensory adaptation (Kuruvilla et al., 1997). We now
      show that this lysozyme response is initiated by a depolarizing chemoreceptor
      potential in Tetrahymena and we have purified the membrane lysozyme receptor by
      affinity chromatography of solubilized Tetrahymena membrane proteins. The
      solubilized, purified protein is 42 kD and it exhibits saturable, high affinity
      lysozyme binding. Polyclonal antibodies raised against this 42 kD receptor block
      the in vivo lysozyme chemoresponse. This is not only the first time that a
      chemoreceptor potential has been recorded from Tetrahymena but also the first
      time that a chemorepellent receptor has been purified from any unicellular
      eukaryote.

PMID- 9516238
TI  - Melatonin enhances tamoxifen's ability to prevent the reduction in microsomal
      membrane fluidity induced by lipid peroxidation.
AB  - The indoleamine melatonin and the synthetic antiestrogenic drug tamoxifen seem to
      have similar mechanisms in inhibiting the growth of estrogen receptor positive
      breast cancer cells. In this study, we compared the ability of these molecules,
      alone and in combination, in stabilizing microsomal membranes against free
      radical attack. Hepatic microsomes were obtained from male rats and incubated
      with or without tamoxifen (50-200 microM), melatonin (1 mM) or both; lipid
      peroxidation was induced by addition of FeCl3, NADPH and ADP. After oxidative
      damage, membrane fluidity, measured by fluorescence polarization techniques,
      decreased whereas malonaldehyde (MDA) and 4-hydroxyalkenals (4-HDA)
      concentrations increased. Incubation of the microsomes with tamoxifen prior to
      exposure to free radical generating processes inhibited, in a dose-dependent
      manner, the increase in membrane rigidity and the rise in MDA + 4-HDA levels.
      When melatonin was added, the efficacy of tamoxifen in preventing membrane
      rigidity was enhanced. Thus, the IC50s for preventing membrane rigidity and for
      inhibiting lipid peroxidation obtained for tamoxifen in the presence of melatonin
      were lower than those obtained with tamoxifen alone. Moreover, tamoxifen (50-200
      microM) in the presence of melatonin reduced basal membrane fluidity and MDA + 4
      HDA levels in microsomes. These synergistic effects of tamoxifen and melatonin in
      stabilizing biological membranes may be important in protecting membranes from
      free radical damage.

PMID- 9516239
TI  - Physiological characterization of the yeast plasma membrane outward rectifying K+
      channel, DUK1 (TOK1), in situ.
AB  - The major voltage-dependent ion channel in the plasma membrane of Saccharomyces
      cerevisiae, a conspicuous outwardly rectifying K+ channel, was first dubbed YPK1
      and later renamed according to its registered gene names (DUK1, TOK1). It has
      proven novel in both structure and function. Whole-cell patch-clamp studies of
      the channel directly on yeast protoplasts now extend our earlier description
      obtained from isolated patches of yeast membrane (Bertl & Slayman, 1992; Bertl et
      al., 1993), and provide new data both on the contributions of channel properties
      to yeast physiology and on possible contributions of molecular structure of
      channel properties. Three recording tactics produce completely equivalent results
      and thereby allow great flexibility in the design of experiments: whole-cell
      voltage clamp with sustained voltage steps (approximately 2.5 sec), whole-cell
      voltage clamp with slow voltage ramps (5 sec, -40 to +100 mV), and time-averaging
      of single-channel currents. Activation of Duk1 channels under steady-state
      conditions is dependent upon ATP in the cytoplasmic solution, and the absence of
      ATP results in channel "rundown"--decreasing numbers of activable channels--over
      periods of 10 min to 1 hr from the start of patch recording. Several putative
      serine- and threonine-phosphorylation sites, as well as a variant ATP-binding
      fold, exist in the molecule as potential mediators of the ATP effects. The
      channel runs down similarly following cytoplasmic acidification, but is almost
      completely insensitive to extracellular pH changes (8.0 to 5.5 tested). This
      remarkable asymmetry may depend on the protein's strongly asymmetric distribution
      of histidine residues, with 10 out of 12 predicted to lie close to the membrane
      cytoplasm interface. Further data confirm the well-recognized observation that
      changes of K+ concentration, intracellular or extracellular, can shift the gating
      voltage of Duk1p in the direction of EK. Among the other alkali-metal cations
      tested, extracellular Rb+ and Cs(+)--but not Na(+)--substitute almost completely
      for K+. Extracellular TEA+ inhibits whole-cell K+ currents through Duk1p with a
      KI of 2.8 mM, and does so probably by reducing the single-channel current.

PMID- 9516241
TI  - Guest Referees

PMID- 9516240
TI  - Nonselective block by La3+ of Arabidopsis ion channels involved in signal
      transduction.
AB  - Lanthanide ions such as La3+ are frequently used as blockers to test the
      involvement of calcium channels in plant and animal signal transduction pathways.
      For example, the large rise in cytoplasmic Ca2+ concentration triggered by cold
      shock in Arabidopsis seedlings is effectively blocked by 10 mM La3+ and we show
      here that the simultaneous large membrane depolarization is similarly blocked.
      However, a pharmacological tool is only as useful as it is selective and the
      specificity of La3+ for calcium channels was brought into question by our finding
      that it also blocked a blue light (BL)-induced depolarization that results from
      anion channel activation and believed not to involve calcium channels. This
      unexpected inhibitory effect of La3+ on the BL-induced depolarization is
      explained by our finding that 10 mM La3+ directly and completely blocked the BL
      activated anion channel when applied to excised patches. We have investigated the
      ability of La3+ to block noncalcium channels in Arabidopsis. In addition to the
      BL-activated anion channel, 10 mM La3+ blocked a cation channel and a stretch
      activated channel in patches of plasma membrane excised from hypocotyl cells. In
      root cells, 10 mM La3+ inhibited the activity of an outward-rectifying potassium
      channel at the whole cell and single-channel level by 47% and 58%, respectively.
      We conclude that La3+ is a nonspecific blocker of multiple ionic conductances in
      Arabidopsis and may disrupt signal transduction processes independently of any
      effect on Ca2+ channels.

PMID- 9516242
TI  - Walking the tightrope: a closer look at managed care.

PMID- 9516243
TI  - Dental insurance coverage for employees of small and large companies.

PMID- 9516244
TI  - Project Mouthguard.
AB  - The increasing incidence of injuries is a major health problem in the United
      States. Many of these injuries are orofacial trauma that result from sports
      activities. The dental profession can play an important role in preventing many
      of these injuries. Working together with athletic trainers, coaches, parents and
      teachers, dental health professionals can help develop effective sports dentistry
      programs in schools and colleges. Project Mouthguard is an example of such a
      coordinated approach to this health problem. By providing custom mouthguards to
      the state's high school athletes and promoting awareness among all Illinois youth
      of the benefits of wearing mouth protection during sports activities, this
      program hopes to significantly reduce the number of orofacial injuries in the
      state.

PMID- 9516245
TI  - Getting paid in the 90's--strategies that work for both practice and patient.

PMID- 9516246
TI  - Independent contractor or employee: beware.

PMID- 9516247
TI  - Public relations campaign to address managed care.

PMID- 9516248
TI  - Hiring dental hygienists in Illinois.

PMID- 9516249
TI  - Bell's palsy: can't whistle, can't spit.

PMID- 9516250
TI  - Rural & urban distribution of dentists, or is there still gold in them thar
      hills?

PMID- 9516251
TI  - Document imaging and the patient chart: envisioning the future for your practice.
AB  - This plan for computerizing the dental patient record is designed to be
      implemented in a stepwise fashion. It assumes a fully developed and well accepted
      practice management system is already present in the business office to ensure
      organizational readiness and a culture embracing technology and its accompanying
      changes. Electronic claims submission is implemented next to not only realize the
      competitive advantages of EDI in the dental office; but also, to introduce the
      process of multi-user communication. Electronic charting in the dental operatory
      is first implemented as a stand alone system. This allows users to understand the
      new workflow requirements and oral exam redesign when a computer is introduced in
      the treatment room. The dental team must understand that the ultimate goal of
      this plan is to network the entire system and enhance communication both within
      and external to the dental office. No specific time requirements were given for
      this plan because of the variability from office to office. People need time to
      develop awareness, prepare for, and become skilled in using new technology.
      Financial constraints may also limit the speed at which the plan can be
      implemented. Finally, individuals in the practice must work together as a team to
      assess the practice's level of acceptance and ability at each step in the
      process. Modification will be necessary along the way as technology is constantly
      changing. This is a significant paradigm shift, considering that many pieces of
      equipment purchased for the dental office can last the dentist's entire career.
      This plan allows for alteration, encourages team involvement and requires a long
      term strategic vision for information technology's role in the dental office.

PMID- 9516252
TI  - What assistants want in the workplace.

PMID- 9516253
TI  - Dental museums and collections in Illinois.

PMID- 9516254
TI  - Dental practices continue to enlarge: even in the state of Illinois.

PMID- 9516255
TI  - Dental technology and the "good-old-days" ethics.

PMID- 9516256
TI  - Future directions in periodontal regeneration therapy--a combined human collagen
      bone multifunctional implant.

PMID- 9516258
TI  - Intranasal conformers: a case report.
AB  - This case report describes the clinical and laboratory procedures in treating a
      patient that was referred to the dental clinic with the chief complaint of
      difficulty of breathing through his nose. Examination of the patient revealed
      constricted nostrils as a result of previous surgeries. It was decided that the
      patient would benefit from construction of intranasal conformers. The conformers
      were constructed from acrylic resin because of the material's durability, ease of
      cleaning, esthetics and ability to be hollowed-out to allow for nasal breathing.
      Alginate molds were used in this case, as this type of mold offers the advantage
      of being reusable. Although this procedure does not fall within the usual area of
      dentistry, members of the dental team may, on occasion, be asked for this
      service.

PMID- 9516257
TI  - ISDS parameters of care document--the dental emergency. Illinois State Dental
      Society.

PMID- 9516259
TI  - Basic techniques for photographing prostheses fabricated in the dental
      laboratory.
AB  - This article will help dental technicians who are amateur photographers choose
      the appropriate camera, lens, lighting, film and background for photographing
      prostheses. A step-by-step photography procedure also is included.

PMID- 9516260
TI  - Laser welding in the dental laboratory: an alternative to soldering.
AB  - Only recently has laser welding been applied to dental technology, primarily as
      an alternative to soldering. This article addresses how the laser is used for
      welding, the effect welding has on metals as the energy is converted into heat
      and reacts with the alloy's surface and the practicality of laser welding in the
      dental laboratory. A step-by-step procedure for accomplishing laser-welded
      connections in a fixed partial denture is included. A laser-welded clasp repair
      using wrought wire and the addition of custom cast parts welded to an existing
      removable partial denture framework on the master model are also shown.

PMID- 9516261
TI  - A spacer that facilitates construction of implant-supported prostheses
      frameworks.
AB  - This article describes a technique that uses polyvinlysiloxane (PVS) putty
      impression material to create adequate space between the tissue and inferior
      margin of a framework in pattern construction for implant supported hybrid
      dentures. This spacer is easily retrieved from the cast, so the dental technician
      can evaluate and adjust the spacer to a standardized thickness and shape it to
      form the framework's underside. Basic framework construction for implant hybrid
      dentures is also reviewed, including specific dimensions, acrylic retentive
      features and passive construction. PVS putty impression material is easy to
      obtain, maintains dimensions well and is easy to shape, making it an excellent
      choice for use as a spacer and a matrix to preserve the position of denture teeth
      during fabrication.

PMID- 9516262
TI  - An intraoral-extraoral combination appliance. A maxillofacial prosthetic device.
AB  - Reconstructing a cancer patient's head and neck region can be challenging for the
      restorative team because of the size of the defect and the tumorous condition of
      the remaining anatomical structures. This article presents a case that uses
      remaining healthy tissue, along with intraoral and extraoral devices, to deliver
      a sophisticated prosthetic device designed to restore physical function.

PMID- 9516263
TI  - An updated guide to characterizing injected dentures.
AB  - This article describes gingival characterization using an injection processing
      and curing technique. The wax-up procedure described in this article duplicates
      natural features such as gingival contours, freni, interdental papillae and
      stippling before investment of the case. The processing and finishing procedure,
      from deflasking to pumicing/polishing to delivery, are described.

PMID- 9516264
TI  - A survey to design the ideal complete denture laboratory prescription.
AB  - Dentists often do not supply the dental laboratory sufficient information to
      select and arrange maxillary denture prosthetic teeth. This article reports
      results from a 1995 survey that asked dental technicians certified in complete
      dentures what elements they would like to see on an ideal dental laboratory
      prescription. With regard to tooth selection, dental technicians rated most
      important on a prescription shade, lip length and shape of face; with regard to
      tooth arrangement, dental technicians rated very important the patient's sex and
      age.

PMID- 9516265
TI  - Maxillary definitive obturators: rationale of design.
AB  - Maxillary definitive obturators are usually fabricated for patients who have an
      acquired defect. The obturators help patients with speech, swallowing,
      mastication, esthetics and psychological well-being. The main goals in restoring
      a maxillary defect with a completely edentulous or partially dentate obturator
      are to provide adequate retention, increased stability and strong vertical
      support. This article addresses the step-by-step fabrication of a maxillary
      obturator that meets these goals.

PMID- 9516266
TI  - Adjustment-free delivery of an immediate, transitional prosthesis.
AB  - A well-designed and properly completed transitional prosthesis can maintain or
      improve function and significantly influence patient confidence and subsequent
      decisions to buy advanced treatment. This article describes the fabrication of an
      immediate, transitional prosthesis that is easily incorporated and functionally
      and esthetically fine-tuned.

PMID- 9516267
TI  - Determining laboratory value: Part 1.
AB  - This article will describe how to determine a fair market value for a dental
      laboratory. Part one addresses how to define fair market value, how value is
      perceived and how to prepare for laboratory evaluation. Part two, to be printed
      in April, will address how to apply an appropriate valuation methodology to
      determine worth.

PMID- 9516268
TI  - A study of solder investment setting and thermal contraction: Part 1.
AB  - In this study, which won the NBC Fellowship Project, the author measured
      expansion and contraction in two soldering and six casting investments to
      determine which are most accurate (defined as marginal gap less than 50
      micrometers and lack of movement with alternating finger pressure) under a number
      of manipulated parameters, including water/powder ratio, setting time, span
      length and burnout temperature. It was determined that all investments
      demonstrated slight expansion between initial and final set. Substantial
      contraction occurred in all investments when subjected to heat. Vestra, CB-30 and
      Cera-Fina demonstrated the greatest contraction at 1500 degrees F. Hi-Heat
      [corrected] (soldering), Quick Set, High Span, Vivest, and Hi-Temp (casting)
      demonstrated greatest contraction at 2000 degrees F. The purpose of the study and
      the methods and materials used are explained in part 1. The results and
      conclusions will be presented in part 2. An introduction to elevated fixturing
      and a verification of the study results will be presented in part 3.

PMID- 9516269
TI  - Metals used to fabricate removable partial denture frameworks.
AB  - This article will help the dental technician choose from among the many alloys
      available for fabricating dental prostheses. It will explain terminology and
      compare and explain inherent properties and characteristics of alloys. Although
      all of the materials discussed produce a clinically acceptable removable partial
      denture framework, the predominantly base alloys dominate the market because of
      the low cost of the metal, case of casting, high yield strength and modulus of
      elasticity.

PMID- 9516270
TI  - Determining laboratory value: Part 2.
AB  - This article describes how to determine a fair market value for a dental
      laboratory. Part one defined fair market value, addressed how value is perceived
      and how to prepare for laboratory evaluation. Part two addresses how to apply an
      appropriate valuation methodology to determine worth.

PMID- 9516271
TI  - Laboratory techniques to prevent screw loosening on dental implants.
AB  - Several factors contribute to the problems of screw loosening on implant
      supported restorations. This article covers specific techniques for processing
      castings made from plastic burnout patterns and gold abutments and copings to
      optimize the connection.

PMID- 9516272
TI  - A study of solder investment setting expansion and thermal contraction: Part 2.
AB  - In this study, which won the NBC Fellowship Project, the author measured
      expansion and contraction in two soldering and six casting investments to
      determine which are most accurate (defined as marginal gap less than 50
      micrometers and lack of movement with alternating finger pressure) under a number
      of manipulated parameters, including water/powder ratio, setting time, span
      length and burnout temperature. It was determined that all investments
      demonstrated slight expansion between initial and final set. Substantial
      contraction occurred in all investments when subjected to heat. Vestra, CB-30 and
      Cera-Fina demonstrated the greatest contraction at 1500 degrees F. Hi-Heat
      (soldering), Quick Set, High Span, Vivest, and Hi-Temp (casting) demonstrated
      greatest contraction at 2000 degrees F. The purpose of the study and the methods
      and materials used were explained in part one, published in March. The results
      and conclusions are presented here. An introduction to elevated fixturing and a
      verification of the study results will be presented in part three.

PMID- 9516273
TI  - A simplified system to develop precision master models.
AB  - Master model construction using a plexiglass base is a procedure used in many
      dental laboratories. The following technique uses the Compact System to create a
      precision master model. This system is functionally superior to pour and base
      techniques because of its improved precision, better placement and improved
      cleanliness of the holes that receive the dowel pins.

PMID- 9516274
TI  - Corrosion of implantable materials and aging of bone.
AB  - This article is a review of how metallic implant corrosion byproducts affect the
      long-term survival of the dental implant bone bed. Cell structure, bone loss,
      metal release and corrosion mechanisms are explained in relation to how they
      influence the metabolic factors that control bone remodeling.

PMID- 9516276
TI  - Dental technology education and professional relations. Interview by Gregory K.
      Boyajian.

PMID- 9516277
TI  - Custom devices for sleep apnea treatment.
AB  - Obstructive sleep apnea (OSA) is a potentially life-threatening sleep disorder
      that is estimated to affect 20 million Americans. OSA is characterized by
      repeated collapse of the upper airway during sleep, which produces breathing
      pauses and interruption of the sleep cycle. Symptoms include heavy snoring, many
      nighttime arousals, sleep deprivation, chronic fatigue and a variety of
      cardiovascular diseases. While many treatments are advocated for OSA, oral
      devices have been shown to be effective. Dental technicians and dentists may be
      involved in the construction of oral appliances for patients with OSA. In this
      article, a synopsis of various treatment modalities is presented, and the
      construction of two appliances is described and illustrated.

PMID- 9516275
TI  - Ergonomics: a case study in preventing repetitive motion injuries.
AB  - Dental Services Group has designed and implemented a system for its dental
      laboratories to mitigate cumulative trauma injuries, such as carpal tunnel
      syndrome and tendinitis. In the dental laboratory, these injuries result from
      repetitive motions such as waxing, sandblasting, grinding and polishing. This
      article describes purchasing guidelines for ergonomically designed laboratory
      equipment and offers resources for implementing workplace safety programs.

PMID- 9516278
TI  - Porcelain-fused-to-metal post and core: an esthetic alternative.
AB  - Custom cast metal post and cores used to retain all-ceramic restorations are
      indicated in endodontically treated teeth when little clinical crown remains. The
      metal cores of these post and core restorations block light transmission and
      create a graying effect when used in support of all-ceramic restorations. This
      article describes a technique to minimize this effect using custom cast porcelain
      fused-to-metal post and cores to achieve a more natural esthetic result.

PMID- 9516279
TI  - Provisionalization of a combination implant/natural abutment restoration.
AB  - This article describes a technique the dental technician can use to fabricate a
      long-term combination implant and natural tooth provisional prosthesis that will
      be used to evaluate esthetics and function. This provisional will act as an
      interim prosthesis while additional implants are healing.

PMID- 9516280
TI  - Eliminating undersized mandibular first premolars.
AB  - Patients are conscious of esthetics and demand natural-appearing dentures. If an
      undersized mandibular first premolar is used in the denture arrangement, the
      result may not be esthetically pleasing. This article will show the dental
      technician how denture arrangements for a Class II jaw relationship can become
      simplified, more predictable and less frustrating by positioning the mandibular
      first molar in a distal occlusion, relative to the maxillary first molar. This
      technique uses zero degree teeth.

PMID- 9516281
TI  - Internet outlook: changing the way laboratories do business.
AB  - This article explores how dental laboratories are taking advantage of the
      Internet's potential. It offers options for web site construction--including in
      house creation vs. using a professional designer--ways to attract new dentist
      clients and ideas for using e-mail to facilitate communication with them, thus
      improving restorations and reducing remakes. Hardware and software necessary for
      an Internet connection is discussed as well as service providers.

PMID- 9516282
TI  - The balancer: principles of design behind Hagman's vintage articulator.

PMID- 9516283
TI  - The enhancement of learning by teaching.

PMID- 9516284
TI  - Clinical informatics and the dental curriculum. A review of the impact of
      informatics in dental care, its implications for dental education.
AB  - The origins of informatics lie in the development of computers and data
      processing techniques since the 1950s. The subsequent application of these to the
      practice of healthcare continues to the present day, so that information
      technology now holds the potential to revolutionise healthcare through more rapid
      and efficient management of an ever increasing quantity of clinical information.
      In dentistry, no less than in medicine, electronic systems can make an extremely
      valuable contribution to clinical practice. For these systems to be clinically
      useful, however, they need to be properly understood by clinicians. This review
      paper outlines the scope of clinical informatics and argues that a grounding in
      clinical informatics is now essential for today's undergraduates to equip them to
      meet the challenge of practice in the 21st century.

PMID- 9516286
TI  - Spanish dental students knowledge of oral malignancy and premalignancy.
AB  - BACKGROUND: In view of the gradual rise in oral malignancy in Europe, there is an
      increased need for undergraduate dental students to have some appropriate
      training in the recognition of the signs and symptoms of oral Premalignancy and
      malignancy, and be aware of the appropriate early management of patients with
      such oral lesions. The present study outlines the results of a pilot study to
      determine the knowledge and awareness of a cohort of undergraduate dental
      students in Spain regarding the management of oral premalignancy and malignancy.
      METHOD: In March 1997 a self-administered questionnaire (SAQ) addressing
      student's knowledge, opinions, and related aspects of screening and detection of
      oral malignancy and premalignancy, was mailed to 200 undergraduate dental
      students in two Spanish Universities. The present report details the responses of
      this cohort of undergraduates. Statistical analysis of the data was performed
      using the chi(2) test and the results were considered significant when P < 0.05.
      RESULTS: 37.0% of the respondents were male and 63.0% female. Almost all of the
      respondents (99.0%) had attended general dental congresses and 81.5% had attended
      specific courses on oral malignancy and premalignancy. Only 20% of undergraduate
      students had witnessed at least one patient with oral malignancy. Squamous cell
      carcinoma (SCC) was the most frequently observed (94.4%) oral tumour. 79% of the
      respondents had examined or witnessed at least one patient with a potentially
      malignant lesion. Leukoplakias were the most commonly observed (80.0%)
      premalignant lesions. 5th year students were more likely to have performed a
      biopsy than 4th year students (P < 0.05), particularly male students (P < 0.005).
      40.0% of respondents believed that the lower lip was the most common site of an
      oral cancer; almost half realised that a tumour could have a speckled appearance.
      79% to 82% of the respondents indicated that tobacco and alcohol were the
      principal causes of oral SCC, but 34.6% suggested that HIV disease was a risk
      factor for oral SCC. Almost all respondents routinely recorded the tobacco or
      alcohol consumption of patients and would offer advice to patients regarding
      modification of these habits. 64.0% of undergraduates suggested that clinical
      screening at intervals of 6 to 12 months was an effective means of diagnosing
      oral premalignant and malignant lesions, and almost all considered oral health
      promotion to be an effective means of reducing oral cancer mortality.
      CONCLUSIONS: Undergraduate dental students in Spain have limited clinical
      experience or knowledge of related aspects of oral premalignant and malignant
      lesions, and they may fail to recognise appropriate signs and symptoms and
      aetiological factors of such disease.

PMID- 9516285
TI  - Stress levels and related variables among dental students in Jerusalem, Israel.
AB  - The aim of the study was to assess levels of stress and associated socio
      demographic variables among dental students in their clinical years in the School
      of Dental Medicine at the Hebrew University and Hadassah in Jerusalem, and
      compare the findings with those of a similar study undertaken 10 years
      previously. The study was carried out among the 4th, 5th and 6th year students
      because these years involve maximum clinical activity. 112 students out of a
      population of 120 participated. Students were asked to complete a 17-item
      anonymous questionnaire composed of items describing potential stressors in the
      learning environment. The quantitative requirement system per completion of
      dental procedures received the highest stress scores among all students (3.15 +/-
      0.82), followed by 'fear from staying behind peers without being able to catch
      up'. The lowest scores were given to 'learning new vocabulary as well as new
      concepts'. These findings were similar to those obtained 10 years ago, despite
      curriculum and social changes in the interim. Based on the median split of the
      population, it was found that among the high-stress group, significantly more
      students evaluated their achievements in school as below average, than did the
      low-stress group (gamma 2, P = 0.017). The % of students who were parents was
      significantly higher among the high-stress group, than the others (P = 0.021).
      Female students reported higher stress in the items comprising 'Clinical work'.
      The results were similar to those of the previous study, despite curricular
      changes introduced in the interim.

PMID- 9516288
TI  - Development, application and effectiveness of a novel logbook checklist
      assessment scheme in conservative dentistry.
AB  - In response to a lack of staff consistency in assessing clinical work, as
      identified by a student questionnaire, a checklist scheme of assessment was
      devised. This consisted of a series of questions covering the key stages of the
      majority of procedures in conservative dentistry to which a demonstrator
      indicates whether each aspect has been completed satisfactorily or not (yes/no)
      giving written comment to enhance the level of immediate feedback. Some 12 months
      following the introduction of the new logbook, a questionnaire was distributed to
      all 42 students who had experienced both this system and a previous ABC grading
      scale for completed work. This consisted of a series of 14 statements and sought
      to compare, for both systems, the clarity of assessment criteria, the relative
      level of staff consistency in applying these, effectiveness of feedback and
      overall meaningfulness of the grades awarded. In addition, in relation to self
      appraisal of performance, both the relevance of this to the practice of dentistry
      together with the degree the logbook facilitated this were assessed. The
      questionnaire return rate was 100%. Compared to the former grading system, the
      new logbook gave a significantly (P < 0.001) more meaningful measure of
      performance, indicated better what was being assessed (P < 0.001) and gave better
      feedback of those points requiring attention to improve performance. In addition,
      the consistency of staff applying the checklist had improved significantly (P <
      0.05) since the introduction of the logbook. It was thus concluded that the
      logbook was a versatile tool in assessment of the clinical skills in conservative
      dentistry.

PMID- 9516287
TI  - Assessment of dental students' ability to recognise precancerous lesions and
      conditions.
AB  - The role of dentists in both primary (promoting a healthier lifestyle) and
      secondary (early diagnosis) prevention of oral cancer is undeniable, and becomes
      particularly important as oral cancer is thought to be preceded by premalignant
      lesions or conditions in about one half of the cases. In these situations, there
      is the possibility for an early diagnosis which will definitively influence the
      survival rate. Thus, it is an undergraduate educational objective related to
      secondary prevention of oral cancer to increase the efficacy of screening of
      precancerous lesions/conditions. A questionnaire with 38 clinical cases including
      16 benign lesions, 9 malignant lesions and 13 precancerous lesions or conditions
      was applied voluntarily to 3rd, 4th and 5th year University of Santiago de
      Compostela dental students on April 1996. The participation rate was 90% of the
      3rd-year students, 60% in 4th-year class, and 50% of the 5th-year group. The
      agreement in the diagnosis with a panel of experts reached 81.45% for 5th-year
      students. Students of 3rd- and 4th-year scored lower percentages, probably due to
      the rarity of some of the conditions in our area. 5th-year students scored
      significantly higher values than 3rd- and 4th-year students.

PMID- 9516289
TI  - Teaching of all-ceramic restorations in central European dental schools: a
      survey.
AB  - The teaching of all-ceramic restorations in Central European dental schools in
      the mid 1990s has been surveyed. Based on a 65% response, the findings indicate
      that the majority of undergraduate (pre-doctoral) students receive instruction in
      all-ceramic restorations with >75% gaining clinical experience in the use of such
      restorations prior to graduation. When clinical experience was not received,
      formal instruction, either in the regular curriculum or in elective studies was
      generally available. All the schools, with one exception, anticipated that the
      importance of teaching all-ceramic restorations would increase or at least stay
      the same. In general, the findings were similar to those reported in studies of
      the teaching of all-ceramic restorations in North America, Scandinavia, and the
      UK and Ireland, especially in relation to luting systems, contraindications and
      finishing instrumentation. However, clinical requirements for all-ceramic
      restorations in Central European dental schools were more common than in dental
      schools in North America, Scandinavia and the UK and Ireland.

PMID- 9516290
TI  - Consideration of special populations in the drug treatment system of a large
      metropolitan area.
AB  - This article provides a descriptive overview of the characteristics of a large
      metropolitan drug treatment system in relation to special populations of
      substance abusers enrolled in the system and the services provided. The findings
      are based on self-report responses to a comprehensive survey of 294 drug
      treatment programs in Los Angeles County. The special populations are grouped by
      health status, ethnic background, language needs, and gender-related needs. The
      groups are not mutually exclusive. Survey results indicated a generally high
      proportion of programs capable of meeting the unique needs of a variety of
      special population clients and most programs having some mix of special
      population clients in their current caseload. The types of services offered
      varied by modality and by special populations being served. Implications for
      program planning and service delivery include consideration of whether or not to
      offer specialized programs for unique client types.

PMID- 9516292
TI  - Utilization management analysis for children's mental health services.
AB  - Efficient identification of high-cost child and adolescent consumers of public
      mental health services using existing utilization and cost data is illustrated,
      along with analyses that profile these high-cost consumers and demonstrate the
      effect on total service cost per client of providing case management. The results
      indicate that providing high levels of case management services is not correlated
      with reductions in total service costs and that there is a need in the service
      system for using high-cost case management review techniques to control service
      utilization and lower costs.

PMID- 9516293
TI  - Collaboration between a state alliance for the mentally ill and a state mental
      health authority in monitoring the consequences of downsizing.
AB  - As consumers are released from hospitalization as a result of the downsizing of
      inpatient psychiatric facilities, their ability to sustain themselves in the
      community becomes a concern to a number of constituencies. This article describes
      the development of a program for monitoring persons who were released from
      hospitals into the community as a result of the downsizing of state psychiatric
      hospitals. The program's uniqueness was the collaboration between the state
      mental health authority and the state Alliance for the Mentally Ill in developing
      and implementing the monitoring system.

PMID- 9516291
TI  - Benefits and costs of supported employment from three perspectives.
AB  - Administrators, consumers, and policy makers are increasingly interested in
      supported employment as a way of helping persons with severe mental illness get
      and keep competitive jobs. However, in an atmosphere of increased expectations
      for performance and declining public financing, administrators want to know the
      costs and benefits of different approaches before they reallocate scarce
      treatment or rehabilitative dollars. This article discusses the net benefits of
      two approaches to supported employment that were compared in a randomized trial:
      Individual Placement and Support (IPS) and Group Skills Training (GST). The
      authors analyze costs and benefits from societal, government, and consumer
      perspectives. Although a previous analysis showed that IPS participants were
      significantly more likely to find work, worked more hours, and had higher
      earnings, net benefits of the two programs were not significantly different. The
      authors also discuss some of the strengths and weaknesses of cost-benefit
      analysis in mental health care and suggest future directions for policy and
      research.

PMID- 9516294
TI  - Using client satisfaction surveys to evaluate and improve services in locked and
      unlocked adult inpatient facilities.
AB  - This article describes the implementation, in five inpatient subacute treatment
      facilities, of a satisfaction survey designed especially for adults with serious
      and persistent mental illnesses. The survey measures not only global satisfaction
      but also client perceptions about different treatment modalities and services,
      important treatment goals, and the philosophy of treatment. Data are presented
      from 770 completed surveys, illustrating patterns of satisfaction across
      facilities and services and patterns over time of stability and change in
      satisfaction. Data are also presented showing how the surveys were used to
      facilitate and measure improvements in clinical services. Finally, the
      implications for mental health services delivery are summarized.

PMID- 9516296
TI  - Services utilization before and after the prospective payment system by patients
      with somatization disorder.
AB  - This study analyzed services utilization before and after the implementation of
      Medicare's Prospective Payment System (PPS) in psychiatric patients with
      somatization disorder in two samples: one recruited before the PPS and the other
      after the PPS. Individuals with this psychiatric disorder present with multiple
      unexplained medical complaints and consume a great number of health resources.
      The results from this study indicated that Medicare PPS was associated with fewer
      hospital admissions and fewer hospital days, with a greater number of physician
      visits (for Medicare patients) and emergency room visits (for non-Medicare
      patients) and with lower overall health expenditures. However, there were no
      significant changes in the average length of stay after PPS. In contrast to
      previous studies, Medicare PPS was significantly associated with changes in
      service utilization by non-Medicare patients as well, a possible "spillover
      effect." This study confirms the results from other research indicating that
      higher levels of efficiency may be achieved for certain psychiatric disorders
      through prospective payment mechanisms.

PMID- 9516295
TI  - An ecological model for school-based mental health services for urban low-income
      aggressive children.
AB  - An ecological model for school-based mental health services that targets urban
      low-income aggressive children--a highly vulnerable and underserved population-
      is presented. The goals of the model are to increase children's and teachers'
      involvement in the delivery of services and to increase the integration of these
      services into existing school resources and activities. The model proposes that
      mental health service providers work in collaboration with teachers to deliver
      services that (1) can be managed by existing school resources and personnel, (2)
      are related to empirically based factors associated with reduced aggression and
      increased social functioning, and (3) are group administered to increase the
      number of children served and to reduce stigmatization associated with mental
      health services. The model is individualized and flexible by acknowledging that
      contexts for aggression differ across classrooms and children and by providing
      services specific to those contexts. Two studies are presented illustrating the
      application of this model to decrease aggression and increase academic engagement
      in low-income urban public schools.

PMID- 9516297
TI  - Mental health and substance abuse treatment services for dually diagnosed
      clients: results of a statewide survey of county administrators.
AB  - Finding are presented from a survey of administrators of county departments of
      mental health and alcohol and drug programs in California regarding services for
      individuals with co-occurring mental and substance abuse disorders. A total of 47
      counties responded (84% response rate). The survey findings indicate that
      collaboration across county mental health and alcohol and drug services primarily
      occurs through information sharing, coordination of services, and joint projects.
      Fewer than one-half of the counties responding provide integrated programs, and
      the most frequently provided services are outpatient counseling and case
      management. Administrators cited historical differences between the two service
      systems and societal stigma as the greatest barriers to service delivery. Two
      opposing strategies for state action were suggested, either establishing specific
      funding set-asides or blending funding for services. Counties varied widely in
      their ability to estimate unmet service needs. Implications for policy
      development related to the dually diagnosed are discussed.

PMID- 9516298
TI  - Oklahoma City: disaster challenges mental health and medical administrators.
AB  - Mental health and medical administrators responded to the Oklahoma City bombing
      with cooperative and overlapping efforts to meet community needs in the wake of
      terrorism. The major agencies assisted in the immediate rescue response,
      organized crisis hotlines, prepared mental health professionals to counsel
      bereaved families and victims, organized debriefing of rescuers, assessed mental
      health needs of local school children, planned for longer term treatment, and
      coordinated research efforts to learn from the disaster. Implications to mental
      health administrators responding to significant acts of terrorism are discussed.

PMID- 9516299
TI  - Developing an integrated information system for specialized addiction treatment
      agencies.
AB  - This article outlines the development of an integrated information system for
      specialized alcohol and drug treatment agencies in Ontario, Canada. The system is
      being developed following a strategic planning process involving provincial
      funding ministries and coalitions of service providers. An overview of the
      system's development is provided and the implementation of one subcomponent, a
      client-tracking system, is described. Some challenges to the implementation of
      this component are identified.

PMID- 9516302
TI  - Faith and healing. Making a place for spirituality.

PMID- 9516300
TI  - Geographic market areas for psychiatric and medical outpatient treatment.
AB  - The research objective was to measure the variation in the size of a facility's
      market areas across different diagnostic categories. Specifically, the market
      area radii for outpatient psychiatric services are compared to the radii for
      outpatient medical services. Data were collected from the outpatient clinics of
      the Little Rock Veterans Administration Medical Center. Visits were categorized
      into 100 diagnostic groups. The market radius for each diagnostic group was
      defined as the 75th quartile of the distribution of distances traveled. All
      psychiatric diagnostic groups had significantly (p < 0.05) smaller market area
      radii than the overall sample radius. The average market area radius across
      psychiatric illnesses was 62.2 miles, which was significantly (p < 0.05) smaller
      than the average radius across medical illnesses (90.6 miles). Results suggest
      that rural patients with mental illness may not receive adequate care and that
      specialized outreach programs may need to be developed to better serve this
      population.

PMID- 9516303
TI  - Nutrition. Deciphering the latest report on trans-fats.

PMID- 9516304
TI  - A cautious comeback for thalidomide.

PMID- 9516305
TI  - Exercise. Water workouts: a low-impact way to stay fit.

PMID- 9516306
TI  - Exercise helps those with heart failure.

PMID- 9516307
TI  - Stress and atherosclerosis.

PMID- 9516308
TI  - An exercise prescription for older people.

PMID- 9516309
TI  - Anti-inflammatory drugs and high blood pressure.

PMID- 9516310
TI  - Winter becoming less dangerous.

PMID- 9516311
TI  - Is wine better than beer for the heart?

PMID- 9516313
TI  - A new source for bypass grafts.

PMID- 9516312
TI  - Getting tough with cholesterol.

PMID- 9516314
TI  - Antidepressant drug helps smoking cessation.

PMID- 9516315
TI  - High altitudes: risky for older people?

PMID- 9516316
TI  - Shooting holes in the heart.

PMID- 9516317
TI  - 'Smart' estrogens emerging.

PMID- 9516318
TI  - Garlic: can it keep your blood vessels young?

PMID- 9516319
TI  - Heart line. Can a chicken be more like a fish?

PMID- 9516320
TI  - The natural history of benign prostatic hyperplasia.

PMID- 9516321
TI  - Margarine, trans-fatty acids, and the heart: a promise not kept.

PMID- 9516323
TI  - Coping with hearing loss.

PMID- 9516322
TI  - Worried sick.

PMID- 9516324
TI  - Shock therapy for depression.

PMID- 9516325
TI  - Having a safe hospital stay.

PMID- 9516326
TI  - AIDS cases and deaths decline.

PMID- 9516328
TI  - Taking care of frostbite.

PMID- 9516327
TI  - Small portions of olestra OK.

PMID- 9516330
TI  - Be wary of bats.

PMID- 9516329
TI  - Too much tick bite testing and treatment.

PMID- 9516331
TI  - Choosing an air cleaner for cigarette smoke.

PMID- 9516332
TI  - Monounsaturates may cut breast cancer risk.

PMID- 9516334
TI  - Physical effects of stress.

PMID- 9516333
TI  - Ladder falls.

PMID- 9516335
TI  - Preventing osteoporosis.

PMID- 9516337
TI  - Getting enough folate and B6?

PMID- 9516336
TI  - Calcium enhances HRT for bones.

PMID- 9516338
TI  - Using your medical family tree.

PMID- 9516339
TI  - BP and weight.

PMID- 9516340
TI  - Light therapy.

PMID- 9516341
TI  - Vegetarian diet pyramid.

PMID- 9516342
TI  - Many wouldn't trade time for better quality of life.

PMID- 9516343
TI  - Surgery for heartburn.

PMID- 9516344
TI  - Tension headaches.

PMID- 9516345
TI  - Extra caution urged for common pesticide.

PMID- 9516346
TI  - Side effects of prostate cancer treatment.

PMID- 9516348
TI  - Incontinence. Ways to help you stay dry.

PMID- 9516347
TI  - Tap water and miscarriage risk.

PMID- 9516349
TI  - Health tips. Removing ear wax.

PMID- 9516350
TI  - Benefits of ginkgo for Alzheimer's are still unclear.

PMID- 9516352
TI  - Healthy weight. Simple tests tell you what shape your shape is in.

PMID- 9516351
TI  - Study points out risks of smoking prior to surgery.

PMID- 9516353
TI  - Hoarse voice. Sometimes your voice is telling you something.

PMID- 9516354
TI  - Iron overload. Early diagnosis can prevent serious damage.

PMID- 9516355
TI  - A friend recommends that I take something called glucosamine for my arthritis.
      What do you know about it?

PMID- 9516356
TI  - My doctor says the small lump on the back of my neck is a lipoma. Should I be
      concerned about it?

PMID- 9516357
TI  - What is dry socket? I'm having my wisdom teeth pulled and was told this might be
      a complication.

PMID- 9516358
TI  - Rotator cuff injuries. When your shoulder throws you a curve.

PMID- 9516359
TI  - Health tips. Relieving dry eyes.

PMID- 9516360
TI  - More evidence that vitamin C may help prevent cataracts.

PMID- 9516361
TI  - Not enough people taking aspirin for heart benefits.

PMID- 9516362
TI  - Balance exercises. Staying steady on your feet.

PMID- 9516363
TI  - Hepatitis C. The surprise infectious disease of the decade.

PMID- 9516364
TI  - Laxatives and constipation. 'Regular' may not be as often as you think.

PMID- 9516365
TI  - I've heard that the nicotine skin patch is a new treatment for ulcerative
      colitis. Is this true?

PMID- 9516366
TI  - Since menopause I've been bothered by vaginal dryness. Is there something that
      can relieve the irritation and prevent discomfort during intercourse?

PMID- 9516367
TI  - Diverticulitis. A byproduct of our refined eating habits.

PMID- 9516368
TI  - Is 'normal' cholesterol OK? Studies say maybe not.

PMID- 9516369
TI  - New drug approved to help prevent osteoporosis.

PMID- 9516370
TI  - Health tips. Exercise adds up.

PMID- 9516371
TI  - Heart attack rehabilitation. Helping your heart heal.

PMID- 9516372
TI  - Bladder cancer. Early detection is critical.

PMID- 9516373
TI  - Dietary fiber. Bulking up your diet can be a healthful decision.

PMID- 9516374
TI  - I got a flu shot, so why did I still get the flu?

PMID- 9516375
TI  - I heard that the adhesive patch you can wear to prevent motion sickness is
      available again. Why was it taken off the market?

PMID- 9516376
TI  - Hematologically important mutations: Gaucher disease.

PMID- 9516377
TI  - Anagrelide for treatment of patients with chronic myelogenous leukemia and a high
      platelet count.
AB  - Chronic myelogenous leukemia (CML) is usually treated with hydroxyurea or
      interferon-alpha. In some patients high platelet counts develop although
      leukocyte counts are well controlled with these drugs. If in such a situation
      cytoreductive therapy has to be intensified by a increase of the dosage, anemia
      and leukocytopenia as well as adverse effects of the drugs are likely to occur.
      In twelve CML patients we have therefore combined the basic CML treatment with
      anagrelide. This drug which selectively reduces platelet counts has been shown to
      be efficacious in the control of thrombocytosis in essential thrombocythemia. The
      diagnosis had been confirmed in all CML patients by cytogenetic and/or molecular
      biological analysis. The median age of our group was 58 years. Five were women
      and seven men. All patients were on treatment with hydroxyurea, some of them had
      previously received treatment with interferon-alpha (alone or in combination with
      hydroxyurea), busulfan or melphalan. Prior to the initiation of anagrelide
      treatment the platelet count was between 970,000 and 3,600, 000/microl (median
      about 2,000,000/microl). Seven patients had thrombohemorrhagic complications. All
      twelve patients, experienced hematologic responses, since their platelet counts
      decreased to less than 600,000/microl. The median platelet count after reduction
      was 343,000/microl. The median dosage required to achieve these responses and to
      maintain them for a period of at least four weeks was 1.9 mg/day.
      Thrombohemorrhagic complications disappeared or did not recur in all symptomatic
      patients. Adverse effects were seen in 3/12 patients: headache (1), tachycardia
      (1), palpitation (1) and fluid retention (1). Whereas these symptoms were mild
      and transitory they caused one patient to request discontinuation of treatment.
      Currently five patients are still on treatment with anagrelide (median duration
      of treatment 11 months) while therapy had to be discontinued in the seven others
      because of bone marrow transplantation, development of osteomyelofibrosis, blast
      crisis or on patient request. In our experience anagrelide is a useful
      therapeutic adjunct when thrombocytosis in patients with CML cannot properly
      controlled alone with traditional drugs.

PMID- 9516378
TI  - Myeloid progenitor cell proliferation and mobilization effects of BB10010, a
      genetically engineered variant of human macrophage inflammatory protein-1alpha,
      in a phase I clinical trial in patients with relapsed/refractory breast cancer.
AB  - Macrophage Inflammatory Protein (MIP)-1alpha is myelosuppressive in vitro and in
      vivo for hematopoietic stem and immature subsets of myeloid progenitor cells,
      demonstrates some myeloprotective effects in mice treated with Ara-C and
      hydroxyurea, and has stem/progenitor cell mobilizing activity in mice. Based on
      these observations, BB10010, a genetic variant of MIP-1alpha, was assessed for
      effects on marrow and blood myeloid progenitor cells in patients with
      relapsed/refractory breast cancer. MIP-1alpha readily polymerizes, whereas
      BB10010 has a reduced tendency to form large polymers at physiological pH and
      ionic strength and retains biological activity. Patients were injected with 5,
      10, 30 or 100 microg/kg BB10010 s.c. daily for 3 days. BB10010 significantly
      reduced the cycling status of marrow myeloid progenitors from pretreatment levels
      of 39-58% to 0 - 11% one day after the third and last injection of BB10010. This
      was associated with significant decreases in frequency of marrow progenitors
      (number of colonies formed per number of cells plated) and percent biopsied
      marrow CD34+ cells. The suppressive effects were reversible in patients and the
      rapidity of this reversal demonstrated in mouse studies. BB10010 had no effect on
      nucleated cellularity or on the proliferation of nucleated cells as assessed in
      marrow biopsies from the patients. These latter effects may in part reflect the
      noted decreased apoptosis of nucleated cells by BB10010. BB10010 also
      demonstrated significant but modest myeloid progenitor cell mobilizing capacity.
      Blood progenitors were in a slow or non-cycling state prior to treatment and this
      did not change after administration of BB10010. The above effects of BB10010 were
      similar at the four different dosage levels assessed. These results demonstrate
      in humans the suppressive and mobilizing effects of MIP-1alpha and BB10010
      previously noted in vivo in mice.

PMID- 9516379
TI  - Molecular identification and expression of erythroid K:Cl cotransporter in human
      and mouse erythroleukemic cells.
AB  - A major pathway for K+ efflux in human reticulocytes and young RBCs is K:Cl
      cotransport (K:Cl-CT). The activity of K:Cl-CT is increased in pathologic RBCs
      containing hemoglobins S and C and may contribute to the abnormal dehydration
      state of these cells. Human K:Cl-CT (gene product KCC1) has been recently
      sequenced from human (hKCC1), rabbit and rat tissue by Gillen et al. (J Biol Chem
      271:16237, 1996). We report here the sequence of KCC1 from human and mouse
      erythroleukemic cells (K562 and MEL cells, respectively). The cDNA for human
      erythroid-KCC1 is 100% identical to hKCC1 and the cDNA for mouse erythroid-KCC1
      shares 89% identity with hKCC1, which translates to 96% identity at the amino
      acid level. Mammalian KCC1 is strongly conserved with >95% identity between
      human, rabbit, rat, and mouse KCC1 proteins. We did not detect any full-length
      mRNA transcripts of human erythroid-KCC1 in circulating reticulocytes. We
      detected two mRNA isoforms of human erythroid-KCC1 that resulted in C-terminal
      truncated proteins (73 amino acid and 17 amino acids, respectively). Human and
      mouse erythroidKCC1 differed at several consensus sites including a predicted PKC
      phosphorylation site at 108threonine and a predicted CK2 phosphorylation site at
      51serine, within the predicted cytoplasmic N-terminal, that are present in human
      but not mouse erythroid-KCC1. Expression of MEL-KCC1 mRNA increases substantially
      upon DMSO-induced differentiation opening the possibility that erythroid-KCC1
      plays a role in early erythroid maturation events. The molecular identification
      of erythroid-KCC1 is an important step towards understanding the physiologic role
      mediated by this protein in young and pathologic RBCs and during erythropoiesis,
      as well as providing a new tool for the elucidation of pathways and signals
      involved in RBC volume regulation.

PMID- 9516380
TI  - Erythroid 5-aminolevulinate synthase is required for erythroid differentiation in
      mouse embryonic stem cells.
AB  - We have examined the induction of the enzymes of the heme biosynthetic pathway
      during erythroid differentiation of mouse embryonic stem (ES) cells. Following
      transfer to appropriate medium all of the pathway enzymes are induced within
      three days. Unlike differentiating mouse erythroleukemia cells (Lake-Bullock, H.
      and Dailey, H.A. Mol Cell Biol 13:7122-7132, 1993), all of the enzymes appear to
      be induced simultaneously and not sequentially in differentiating ES cells. The
      role of erythroid 5-aminolevulinate synthase (ALAS-2) in this differentiation
      process was examined by disruption of the ALAS-2 gene. The targeting vector used
      for disruption replaced all of exons 4 to 6 with a selectable neomycin resistance
      gene. The resulting genetically modified (ALAS-2 knockout) cells, as well as
      normal ES cells were used to study induction of heme biosynthesis. Following 10
      days of culture in methylcellulose media significant morphological differences
      between the embryoid bodies (EBs) of the two cell lines were observed. ES cells
      exhibited morphology of typical EBs with a dark field (blood island) in the
      center, while ALAS-2 knockout ES cells developed very poorly both in size and
      shape. At 8 days of differentiation, only 3% of all EBs contained visible
      erythropoietic cells (i.e., stained positively for hemoglobin) in the ALAS-2
      knockout cell line, compared with 50% in ES cells. Most of the genes in the heme
      synthetic pathway were expressed to a stable level within 3 to 6 days after
      induction in normal ES cells, while the ALAS-2 knockout cell line failed to
      significantly increase the level of expression of these genes. Fetal beta-globin
      mRNA was not detectable in the differentiating ALAS-2 knockout cells, whereas
      mRNA for this gene was detected in normal ES cells within 3 days of
      differentiation. These results suggest that ALAS-2 is necessary for ES cell
      erythroid differentiation and that there is an interrelationship between heme and
      globin synthesis in differentiating ES cells.

PMID- 9516381
TI  - DNA inverted repeats and human disease.
AB  - Inverted repeats are important elements in the human genome. Because of their
      nature, inverted repeats can engage in intra- and intermolecular basepairing. The
      ability to adopt hairpin and cruciform secondary structures is associated with
      frameshift mutations. These sequences also can be utilized by the polymerase
      allowing both intra- and interstrand switching events. Such mechanisms can
      involve imperfect inverted repeats and lead to additional mutations. Several
      human genetic diseases illustrate inverted repeat mediated mutagenesis.

PMID- 9516382
TI  - Inflammation and intestinal metaplasia of the gastric cardia: the role of
      gastroesophageal reflux and H. pylori infection.
AB  - BACKGROUND & AIMS: Whether inflammation of the cardia indicates gastroesophageal
      reflux disease (GERD) and/or is a manifestation of pangastritis caused by
      Helicobacter pylori infection is unknown. The aim of this study was to evaluate
      the relationship between cardia inflammation, H. pylori infection, and cardia
      intestinal metaplasia in patients with and without GERD. METHODS: Patients with
      GERD were compared with controls undergoing endoscopy for a variety of other
      conditions. Endoscopic biopsy specimens from the distal esophagus and cardia,
      fundus, and antrum were evaluated for inflammation, H. pylori infection, and
      intestinal metaplasia. RESULTS: Neither the prevalence of H. pylori infection
      (controls, 48%; GERD, 41%) nor cardia inflammation (controls, 41%; GERD, 40%)
      differed between groups. All 11 controls and 22 of 23 patients with GERD (96%)
      and cardia inflammation had H. pylori infection. Esophagitis was more common
      among GERD patients (33%) than controls (7%; P = 0.01). Cardia intestinal
      metaplasia was more common among controls (22%) than GERD patients (3%; P =
      0.01); all had cardia inflammation, 7 had H. pylori infection, and 6 had
      metaplasia elsewhere in the stomach. CONCLUSIONS: The prevalence of cardia
      inflammation is similar in patients with and without GERD and is associated with
      H. pylori infection (P < 0.001). Cardia intestinal metaplasia is associated with
      H. pylori-related cardia inflammation (P = 0.01) and intestinal metaplasia
      elsewhere in the stomach, indicating that it is distinct from Barrett's
      esophagus.

PMID- 9516383
TI  - McBurney of McBurney's point.

PMID- 9516384
TI  - Release of mast cell mediators into the jejunum by cold pain stress in humans.
AB  - BACKGROUND & AIMS: The central nervous system regulates gut functions via complex
      interactions between the enteric nervous and immune systems. The aim of this
      study was to investigate whether mast cell mediators are released into the human
      jejunal lumen during stress. METHODS: A closed-segment perfusion technique was
      used to investigate jejunal release of tryptase, histamine, prostaglandin D2, and
      water flux in response to the cold pressor test in 8 healthy subjects and 9
      patients with food allergy. In 6 food-allergic patients, jejunal biochemical
      responses to cold pain stress were compared with those induced by food
      intraluminal challenge. RESULTS: Cold pain stress elevated heart rate and blood
      pressure and increased luminal release of mast cell mediators and jejunal water
      secretion in both groups. Stress-induced release of tryptase and histamine, but
      not of prostaglandin D2 and water flux, was greater in food-allergic patients
      than in healthy volunteers. In food-allergic patients, jejunal biochemical
      responses induced by cold pain stress were similar to those induced by antigen
      challenge. CONCLUSIONS: These results show the ability of the central nervous
      system to modulate intestinal mast cell activity and suggest that mast cells have
      a role in stress-related gut dysfunction.

PMID- 9516385
TI  - Major histocompatibility complex class II-dependent antigen presentation by human
      intestinal endothelial cells.
AB  - BACKGROUND & AIMS: In the normal gut, human intestinal microvascular endothelial
      cells (HIMECs) express major histocompatibility complex (MHC) class II molecules.
      Enhanced expression is found in chronic inflammation. We examined the cytokine
      regulation of MHC class II molecules and the associated invariant chain (Ii) in
      HIMECs and investigated whether such cells can process and present a complex
      protein antigen to T cells. METHODS: Enzyme-linked immunosorbent assay, flow
      cytometry, immunoelectron microscopy, as well as T-cell activation assay with
      HIMECs and HLA-DR-restricted T-cell clones were employed. RESULTS: In
      unstimulated HIMEC monolayers, HLA-DR, -DP, and -DQ and Ii were undetectable at
      the protein level, but interferon gamma (IFN-gamma) (100 U/mL) induced expression
      that peaked for DR after 2-3 days, for DP after 4-6 days, for DQ after 10-12
      days, and for Ii after 2-3 days. Tumor necrosis factor alpha had no effect alone
      but enhanced class II expression in combination with IFN-gamma, most notably for
      DQ and DP. HLA-DR3-restricted and Mycobacterium tuberculosis heat shock 65
      kilodalton-specific T-cell clones were activated to produce IFN-gamma in response
      to relevant antigen presented by IFN-gamma-treated HIMECs. This response was
      inhibited by blocking monoclonal antibody to HLA-DR and by chloroquine when
      compared to professional antigen-presenting cells, HIMECs activated T-cell clones
      quite efficiently. CONCLUSIONS: These data suggest that microvascular endothelial
      cells can present complex protein antigens in the human gut.

PMID- 9516386
TI  - Autocrine regulation of epithelial permeability by hypoxia: role for polarized
      release of tumor necrosis factor alpha.
AB  - BACKGROUND & AIMS: The intestinal mucosa is lined by a monolayer of protective
      epithelial cells. This barrier is regulated by immune-derived factors such as
      interferon gamma (IFN-gamma). Because of the high volume of blood flow, the
      intestine is a primary target for hypoxic damage. We hypothesize that epithelial
      cytokine responses are regulated by hypoxia. METHODS: T84 intestinal epithelial
      cells were used to assess alterations in permeability, major histocompatibility
      complex class II induction, cytokine receptor expression, and cytokine release in
      response to combinations of IFN-gamma and cellular hypoxia. RESULTS: Hypoxia
      potentiated the influence of IFN-gamma on epithelial barrier function. Such
      responses were conferrable in a >/=10-kilodalton conditioned media fraction from
      hypoxic epithelia. Subsequent experiments identified this factor as epithelium
      derived tumor necrosis factor alpha (TNF-alpha). Add-back of recombinant TNF
      alpha in combination with IFN-gamma to normoxic epithelia recapitulated hypoxia
      and identified basolaterally polarized TNF-alpha receptor types I and II on
      intestinal epithelia. A similar pattern of TNF-alpha-receptor expression was
      observed on native intestinal epithelia. Specific inhibition of TNF-alpha using
      neutralizing antibody or alpha-N-phthalimidoglutarimide (thalidomide) resulted in
      reversal of the hypoxia-evoked responses. CONCLUSIONS: These studies indicate
      that during hypoxia, epithelium-derived mediators such as TNF-alpha have the
      potential to regulate permeability through autocrine pathways.

PMID- 9516387
TI  - Family history as a risk factor for ulcerative colitis-associated colon cancer in
      cotton-top tamarin.
AB  - BACKGROUND & AIMS: Little is currently known about the relationship between
      family history of colon cancer and ulcerative colitis-associated colon cancer. A
      nested case-control study was performed to evaluate the association between
      family history of colon cancer and spontaneously occurring colon cancer in cotton
      top tamarins (Saguinus oedipus). METHODS: Subjects were chosen from a colony of
      cotton-top tamarins held in captivity between 1968 and 1995. The cancer status of
      parents and grandparents was compared for 48 animals with colon cancer and 58
      controls, all with histological confirmation of ulcerative colitis. Multivariate
      odds ratios were calculated using logistic regression. RESULTS: A parental
      history of colon cancer was positively associated with risk of colon cancer
      (multivariate odds ratio, 2.7; 95% confidence interval, 1.1-6.3). Risk also
      increased as an animal's total number of family members with colon cancer
      increased (multivariate odds ratio, 1.7 for each increase in the total number of
      family members with cancer; 95% confidence interval, 1.1-2.8). CONCLUSIONS: The
      results suggest that cotton-top tamarins with ulcerative colitis are at
      significant increased risk for developing colon cancer if they have a family
      history of colon cancer. Further investigation of this relationship in both
      tamarins and humans is warranted.

PMID- 9516388
TI  - Mice lacking secretory phospholipase A2 show altered apoptosis and
      differentiation with Helicobacter felis infection.
AB  - BACKGROUND & AIMS: Infection with Helicobacter pylori uniformly leads to a
      chronic superficial gastritis that may progress to atrophic gastritis, a
      premalignant process. A mouse model of Helicobacter felis infection was used to
      study possible genetic determinants of the response to infection. METHODS: Three
      inbred mouse strains with known secretory phospholipase A2 (sPLA2) genotypes
      [BALB/c (+/+), C3H/HeJ (+/+), and C57BL/6 (-/-)] were orally infected with H.
      felis and examined longitudinally using routine histology, immunocytochemistry,
      electron microscopy, proliferating cell nuclear antigen, terminal
      deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end
      labeling, and Northern and Western blot studies. RESULTS: Only the C57BL/6 strain
      showed increased gastric fundic proliferation and apoptosis in response to
      infection. In addition, the C57BL/6 mouse showed a marked loss of parietal and
      chief cells, along with a marked expansion of an aberrant gastric mucous cell
      lineage that stained positive for spasmolytic polypeptide. In contrast, no
      significant change in these cell types was observed in BALB/c and C3H/HeJ
      strains. Increased expression of sPLA2 was observed in BALB/c and C3H/HeJ after
      H. felis infection, whereas sPLA2 expression was absent in C57BL/6 mice.
      CONCLUSIONS: H. felis infection leads to increased apoptosis and altered cellular
      differentiation in the C57BL/6 mouse, a strain that lacks gastric sPLA2
      expression. Because sPLA2 has been identified recently as the MOM1 (modifier of
      MIN) locus that influences polyp formation in the colon, these studies suggest
      that sPLA2 may also influence the gastric epithelial response to Helicobacter
      infection.

PMID- 9516389
TI  - Molecular mimicry of ferret gastric epithelial blood group antigen A by
      Helicobacter mustelae.
AB  - BACKGROUND & AIMS: Molecular mimicry of Lewis blood group antigens by
      Helicobacter pylori may be involved in immune evasion by the bacteria and in the
      pathogenesis of chronic atrophic gastritis. Helicobacter mustelae infects ferrets
      naturally, causing gastritis, and may be involved in ulcerogenesis. The aim of
      this study was to determine if H. mustelae shows a similar form of molecular
      mimicry. METHODS: Antibodies raised against H. mustelae were used to stain ferret
      gastric tissue by immunoblotting, immunohistochemistry, and flow cytometry.
      Epitopes recognized by cross-reactivity were characterized by proteinase K and
      sodium metaperiodate treatment. RESULTS: H. mustelae antiserum reacted with H.
      mustelae and with ferret gastric tissue. Absorption of the antiserum with H.
      mustelae or ferret and rabbit gastric tissue removed the cross-reactive
      antibodies. Antibodies reacted with a blood group antigen A-like structure on
      ferret gastric epithelial cells and H. mustelae lipopolysaccharide. CONCLUSIONS:
      H. mustelae expresses a blood group-like antigen as part of its
      lipopolysaccharide that may be used as a method of immune evasion by mimicry of
      gastric epithelial cells. The cross-reactivity shown by H. mustelae-specific
      antibodies with gastric mucosa may suggest a role for autoantibodies in the
      pathogenesis of H. mustelae-induced gastritis in ferrets.

PMID- 9516390
TI  - Rapid mitogen-activated protein kinase activation by transforming growth factor
      alpha in wounded rat intestinal epithelial cells.
AB  - BACKGROUND & AIMS: To define signaling events initiating healing after intestinal
      epithelial injury, activation of mitogen-activated protein kinase (MAPK) pathways
      was assessed after wounding using an in vitro model. METHODS: Proteins isolated
      from wounded monolayers of nontransformed intestinal epithelial cells (IEC-6)
      were analyzed for tyrosine phosphorylation and MAPK expression by Western blot.
      Extracellular signal-regulated kinase (ERK) 1, ERK2, and Raf-1 activities were
      assessed by immune complex kinase assays. RESULTS: Tyrosine phosphorylation of
      several proteins including ERK1 was substantially increased 5 minutes after
      injury. Another MAPK, c-Jun-N-terminal protein kinase (JNK), was also activated
      after wounding. Conditioned medium from wounded but not intact IEC-6 monolayers
      resulted in increased activity of ERK1, ERK2, and Raf-1 kinase. Wound-conditioned
      medium stimulated proliferation of subconfluent IEC-6 cells compared with
      conditioned medium from intact IEC-6 cultures and contained higher amounts of
      transforming growth factor (TGF)-alpha than supernatants of confluent IEC-6
      cultures. Activation of ERK1 and ERK2 was partially inhibited by neutralizing
      anti-TGF-alpha. CONCLUSIONS: Wounding of intestinal epithelial cells results in
      activation of Raf-1, ERK1, ERK2, and JNK1 MAPKs and subsequent cell proliferation
      in vitro. Activation of ERK1 and ERK2 is mediated in part by TGF-alpha.

PMID- 9516391
TI  - Induction of mitogen-activated protein kinase signal transduction pathway during
      gastric ulcer healing in rats.
AB  - BACKGROUND & AIMS: Previous studies have shown that gastric ulceration stimulates
      epithelial cell proliferation and overexpression of epidermal growth factor (EGF)
      and EGF receptor (EGF-R) in the mucosa bordering necrosis. The aim of this study
      was to investigate whether extracellular signal-regulated kinase (ERK) cascade is
      involved in the healing of experimental gastric ulcers. METHODS: We studied EGF-R
      levels, EGF-R phosphorylation levels, and ERK1 and ERK2 activity in normal and
      ulcerated rat gastric mucosa. We also examined the effect of Tyrphostin A46
      (potent inhibitor of EGF-R and EGF-R kinase-dependent proliferation) on the above
      parameters. RESULTS: During the initial stages of healing (3 and 7 days),
      ulcerated mucosa showed significant increase (vs. controls) in protein tyrosine
      kinase activity, EGF-R levels (510% and 550%), EGF-R phosphorylation levels, ERK1
      activity (430% and 880%), and ERK2 activity (550% and 990%). Tyrphostin A46
      treatment significantly inhibited ulcer healing and reduced EGF-R levels, EGF-R
      phosphorylation, and ERK1 and ERK2 activity. CONCLUSIONS: These findings indicate
      that experimental gastric ulcer healing involves activation of EGF-R-ERK signal
      transduction pathway.

PMID- 9516392
TI  - Regulation of the PepT1 peptide transporter in the rat small intestine in
      response to 5-fluorouracil-induced injury.
AB  - BACKGROUND & AIMS: The oligopeptide transport system of the small intestine is
      resistant to mucosal injury. The mechanism of this resistance was investigated by
      examining the activity level and expression of the peptide transporter PepT1 in
      the intestine of rats treated with 5-fluorouracil. METHODS: The expression and
      localization of PepT1 were examined by immunoblot analysis of brush border
      membrane vesicles and immunohistochemical analysis of intestinal sections with
      PepT1-specific rabbit polyclonal antibodies. Also, Northern blot analysis was
      used for the expression of PepT1 messenger RNA (mRNA). RESULTS: Although the
      amounts of sucrase and an Na+-dependent glucose transporter protein in intestinal
      vesicles decreased markedly after 5-fluorouracil treatment, the amount of PepT1
      protein remained largely unaffected. Immunohistochemical analysis also showed
      that the PepT1 immunoreactivity level was preserved in the brush border membrane
      of the remaining villi of 5-fluorouracil-treated rats. Levels of amino acid,
      glucose, and phosphate transporter mRNAs were profoundly depressed in 5
      fluorouracil-treated animals, whereas the level of PepT1 mRNA conversely
      increased. CONCLUSIONS: The resistance of intestinal peptide transport to tissue
      injury may be attributable to increased synthesis of PepT1 rather than to a
      change in the kinetic properties of the residual absorbing cells.

PMID- 9516393
TI  - Interstitial cells of cajal direct normal propulsive contractile activity in the
      mouse small intestine.
AB  - BACKGROUND & AIMS: Interstitial cells of Cajal (ICC) have been linked to the
      generation of intestinal pacemaker activity, but their role in in vivo motor
      dysfunction is unclear. In this study, we investigated the hypothesis that ICC
      play a role in the generation of distention-induced peristalsis using W/Wv mice
      that lack ICC associated with Auerbach's plexus. METHODS: Radiological
      observations were made of the movement of contrast fluid through the proximal
      small intestine. Electrical activities were recorded in the external muscle
      layers. In addition, intraluminal pressure changes were recorded in isolated
      intestinal segments. RESULTS: In control mice, after gavage of 0.5 mL of barium
      sulfate in the stomach, the contrast fluid moved through the proximal small
      intestine in peristaltic waves at approximately 47 times a minute, propagating
      aborally at approximately 2 cm/s. Electrical slow waves and intraluminal pressure
      waves were synchronized at similar frequencies and propagation velocities. In
      W/Wv mice, such regular peristaltic waves were not observed. Action potentials
      and contractions appeared random, and contents moved back and forth in an
      irregular manner. The net propulsive effect of contractile activity in W/Wv
      mutant mice was much weaker than that in controls. CONCLUSIONS: Slow wave
      controlled peristalsis occurs in the normal proximal small intestine upon gastric
      emptying of a semiliquid. This motor pattern is absent in W/Wv mice that lack
      ICC.

PMID- 9516394
TI  - Short-chain fatty acids have polarized effects on sodium transport and
      intracellular pH in rabbit proximal colon.
AB  - BACKGROUND & AIMS: Short-chain fatty acids (SCFAs) stimulate colonic Na+
      absorption, presumably by acidification of colonocytes and activation of apical
      Na+/H+ exchangers. It is unclear whether this effect depends on SCFA gradients
      across the colonic epithelium, and, if so, why. The aim of this study was to
      determine (1) whether SCFAs added unilaterally to either the apical or
      basolateral border of the cell have similar effects on intracellular pH (pHi);
      (2) whether SCFA gradients alter Na+ transport and; (3) what regulatory factors
      are involved in gradient-induced Na+ transport. METHODS: pHi was measured in
      intact epithelial rabbit proximal colon using the pH-sensitive indicator 2',7'
      bis(carboxyethyl)-5-(6)-carboxyfluorescein, and Na+ transport was measured under
      short-circuit conditions. RESULTS: Apical and basolateral SCFAs had equivalent
      effects on decreasing pHi, but the recovery toward baseline was more vigorous
      after apical SCFAs. Gradients of both propionate and lactate (50 mmol/L
      [mucosal], 0 mmol/L [serosal]) stimulated electroneutral Na+ absorption, which
      was inhibited by bicarbonate, mucosal 4,4'-diisothiocyanostilbene-2, 2'
      disulfonic acid, and Cl- removal. However, it was not blocked by amiloride. The
      differential response to a series of pharmacological agents showed that gradient
      stimulated transport is distinct from epinephrine-stimulated electroneutral Na+
      absorption. CONCLUSIONS: A physiological gradient of SCFAs across the colonic
      epithelium elicits polarized effects on both pHi and Na+ absorption that may be
      important determinants of colonic fluid transport.

PMID- 9516395
TI  - Effect of motilin and erythromycin on calcium-activated potassium channels in
      rabbit colonic myocytes.
AB  - BACKGROUND & AIMS: Motilin and erythromycin are prokinetic agents that act on the
      same receptor in gastrointestinal smooth muscle to cause contraction. Both
      agonists may also cause an increase in outward current. The aim of this study was
      to determine whether motilin and erythromycin activate calcium-activated
      potassium (KCa) channels. METHODS: Freshly dispersed longitudinal smooth muscle
      cells of the rabbit colon were used to measure whole-cell outward current and
      single-channel activity using patch clamp recording methods. RESULTS:
      Erythromycin and motilin increased a calcium-dependent outward potassium current
      and increased the open probability of KCa channels of cell- attached patches.
      CONCLUSIONS: Erythromycin and motilin activate KCa channels via an intracellular
      second messenger system. This effect may modulate the increase in contractility
      caused by these agonists.

PMID- 9516396
TI  - Hepatic Helicobacter species identified in bile and gallbladder tissue from
      Chileans with chronic cholecystitis.
AB  - BACKGROUND & AIMS: Cancer of the gallbladder is the number one cause of cancer
      mortality in Chilean women. Incidence rates for this tumor vary widely on a
      worldwide basis, being approximately 30 times higher in high-risk than in low
      risk populations, suggesting that environmental factors such as infectious
      microorganisms, carcinogens, and nutrition play a role in its pathogenesis.
      Because several Helicobacter sp. colonize the livers of animals and induce
      hepatitis, the aim of this study was to determine whether Helicobacter infection
      was associated with cholecystitis in humans. METHODS: Bile or resected
      gallbladder tissue from 46 Chileans with chronic cholecystitis undergoing
      cholecystectomy were cultured for Helicobacter sp. and subjected to polymerase
      chain reaction (PCR) analysis using Helicobacter-specific 16S ribosomal RNA
      primers. RESULTS: Recovery of Helicobacter sp. from frozen specimens was
      unsuccessful. However, by PCR analysis, 13 of 23 bile samples and 9 of 23
      gallbladder tissues were positive for Helicobacter. Eight of the Helicobacter
      specific PCR amplicons were sequenced and subjected to phylogenetic analysis.
      Five sequences represented strains of H. bilis, two strains of "Flexispira
      rappini" (ATCC 49317), and one strain of H. pullorum. CONCLUSIONS: These data
      support an association of bile-resistant Helicobacter sp. with gallbladder
      disease. Further studies are needed to ascertain whether similar Helicobacter sp.
      play a causative role in the development of gallbladder cancer.

PMID- 9516397
TI  - Steatohepatitis-inducing drugs cause mitochondrial dysfunction and lipid
      peroxidation in rat hepatocytes.
AB  - BACKGROUND & AIMS: 4,4'-Diethylaminoethoxyhexestrol (DEAEH), amiodarone, and
      perhexiline cause steatohepatitis in humans. The mechanisms of these effects are
      unknown for DEAEH and have not been completely elucidated for amiodarone and
      perhexiline. The aim of this study was to determine these mechanisms. METHODS:
      Rat liver mitochondria, cultured rat hepatocytes, or rats were treated with these
      drugs, and the effects on mitochondrial respiration, beta-oxidation, reactive
      oxygen species formation, and lipid peroxidation were determined. RESULTS: DEAEH
      accumulated in mitochondria and inhibited carnitine palmitoyl transferase I and
      acyl-coenzyme A dehydrogenases; it decreased beta-oxidation and caused lipid
      deposits in hepatocytes. DEAEH also inhibited mitochondrial respiration and
      decreased adenosine triphosphate (ATP) levels in hepatocytes. DEAEH, amiodarone,
      and perhexiline augmented the mitochondrial formation of reactive oxygen species
      and caused lipid peroxidation in rats. CONCLUSIONS: Like amiodarone and
      perhexiline, DEAEH accumulates in mitochondria, where it inhibits both beta
      oxidation (causing steatosis) and respiration. Inhibition of respiration
      decreases ATP and also increases the mitochondrial formation of reactive oxygen
      species. The latter oxidize fat deposits, causing lipid peroxidation. We suggest
      that ATP depletion and lipid peroxidation may cause cell death and that lipid
      peroxidation products may account, in part, for other steatohepatitis lesions.

PMID- 9516399
TI  - Stimulation of cyclic guanosine monophosphate production by natriuretic peptide
      in human biliary cells.
AB  - BACKGROUND & AIMS: Guanosine 3',5'-cyclic monophosphate (cGMP), whose production
      is stimulated by the interaction of nitric oxide, natriuretic peptides, and
      guanylin with their respective guanylate cyclases, activates secretion through
      ion channels in several epithelia. Cl- channels have been identified in the
      apical membrane of biliary epithelial cells. The aim of this study was to
      investigate the production of cGMP and its effects on Cl- permeability in biliary
      epithelial cells. METHODS: Halide efflux measurement, whole-cell patch clamp
      recording, radioimmunoassay, and reverse-transcription polymerase chain reaction
      using two human biliary cell lines (H69 and Mz-ChA-1) were performed. RESULTS: In
      cells equilibrated with 125I, bromo-cGMP stimulated halide efflux by 22%. In
      whole-cell patch clamp recordings, the addition of cGMP intracellularly, or of
      atrial natriuretic peptide extracellularly, stimulated inward currents at
      negative membrane potentials, consistent with Cl- efflux through open channels.
      In H69 cells, atrial and C-type natriuretic peptides stimulated production of
      cGMP. Mz-ChA-1 responded only to atrial natriuretic peptide. Both cell lines
      expressed messenger RNA for the guanylate cyclase type A receptor and the
      guanylate cyclase free-clearance receptor. CONCLUSIONS: These data suggest that
      natriuretic peptide stimulates cGMP production in human biliary epithelial cells,
      which in turn may regulate ductular bile formation through the opening of Cl-
      channels.

PMID- 9516398
TI  - Hepatocyte growth factor stimulates DNA synthesis in rat preneoplastic
      hepatocytes but not in liver carcinoma cells.
AB  - BACKGROUND & AIMS: It is not well clarified whether hepatocyte growth factor
      (HGF) stimulates the growth of preneoplastic hepatocytes and liver carcinoma
      cells in vivo. The effect of HGF on in vivo DNA synthesis in these cells and also
      its effect on tyrosine phosphorylation of the HGF receptor protein (c-Met) in
      liver carcinoma were examined. METHODS: Lesions were induced in rats using 3'
      methyl-4-dimethylaminoazobenzene (3'-Me-DAB). The rats were given intravenous
      recombinant human HGF or vehicle, and DNA synthesis was assessed by the 5-bromo
      2'-deoxyuridine labeling index. Tyrosine phosphorylation of c-Met by HGF was
      analyzed by Western blot. RESULTS: The labeling indices were significantly higher
      in the HGF group than in the vehicle control group in altered foci and
      hyperplastic nodules (preneoplastic hepatic lesions). No significant differences
      in the labeling indices were observed between the two groups with carcinoma.
      Tyrosine phosphorylation of c-Met in carcinoma cells was unaffected by HGF
      administration. CONCLUSIONS: HGF promotes the growth of preneoplastic hepatocytes
      but does not affect the growth of liver carcinoma cells in 3'-Me-DAB-treated
      rats.

PMID- 9516400
TI  - Guanylin stimulates regulated secretion from human neuroendocrine pancreatic
      cells.
AB  - BACKGROUND & AIMS: Gastroenteropancreatic neuroendocrine cells secrete chemical
      messengers in a calcium-dependent fashion. So far, other second messenger systems
      involved in regulated secretion have gained little attention. The aim of this
      study was to characterize guanosine 3',5'-cyclic monophosphate (cGMP)-mediated
      vesicular secretion in pancreatic neuroendocrine cells. METHODS: In a human
      pancreatic cell line, BON, cyclic nucleotide levels and chromogranin A release
      were monitored with specific immunoassays. Uptake and release of gamma
      aminobutyric acid were measured. Intracellular Ca2+ concentration was monitored
      with fura-2. Guanylyl cyclase C was analyzed by reverse-transcription polymerase
      chain reaction. RESULTS: Guanylin increased cGMP concentrations in BON cells via
      guanylyl cyclase C. Stimulation of the cGMP pathway by guanylin or Escherichia
      coli heat-stable enterotoxin increased the release of chromogranin A and gamma
      aminobutyric acid from BON cells. This effect was mimicked by the cGMP analogue 8
      bromo-cGMP. CONCLUSIONS: Guanylin and STa stimulate the regulated secretion from
      BON cells via guanylyl cyclase C and cGMP. Our study yields novel information
      about secretory properties of guanylin, mediated via a signal transduction
      pathway, increasing cGMP and leading to regulated secretion of neuroendocrine
      cells.

PMID- 9516401
TI  - Suppression of fibroblast growth factor receptor signaling inhibits pancreatic
      cancer growth in vitro and in vivo.
AB  - BACKGROUND & AIMS: Fibroblast growth factors (FGFs) are mitogenic polypeptides
      that activate specific cell surface FGF receptors (FGFRs). Pancreatic cancers
      overexpress basic FGF (bFGF) and the type I FGF receptor (FGFR-1), and
      overexpression of bFGF has been correlated with decreased patient survival. The
      aim of this study was to examine the effects of abrogation of FGFR-1-dependent
      signaling on pancreatic cancer cell growth. METHODS: PANC-1 human pancreatic
      cancer cells were transfected with a truncated FGFR-1 complementary DNA
      (FGFR405), resulting in the expression of a kinase-deficient receptor. Activation
      of endogenous FGFR-1 was assessed in immunoblot studies with antiphosphotyrosine
      and anti-active mitogen-activated protein (MAP) kinase antibodies. Effects on
      cell growth were determined in vitro and in nude mice. RESULTS: PANC-1 clones
      expressing the truncated receptor showed attenuated receptor tyrosine
      phosphorylation and MAP kinase activation in response to bFGF, decreased basal
      cell growth, and a marked decrease in tumor-forming potential in vivo.
      Confirmatory experiments with MIA PaCa-2 pancreatic cancer cells indicated that
      FGFR405 also attenuated FGF-dependent MAP kinase activation in this cell line.
      CONCLUSIONS: The findings suggest that FGFR-dependent signaling is crucial for
      pancreatic cancer growth and raise the possibility that inhibition of FGFR
      signaling may ultimately prove useful as a therapeutic option in patients with
      pancreatic cancer.

PMID- 9516402
TI  - The pancreatitis-associated protein is induced by free radicals in AR4-2J cells
      and confers cell resistance to apoptosis.
AB  - BACKGROUND & AIMS: Free radicals are involved in the pathogenesis of acute
      pancreatitis, during which pancreatitis-associated protein (PAP)-I is
      overexpressed. We explored whether PAP-I expression could be induced by oxidative
      stress and whether it could affect apoptosis. METHODS: AR4-2J cells were exposed
      to H2O2 or menadione, and PAP-I messenger RNA (mRNA) expression was analyzed by
      Northern blotting. RESULTS: Maximal expression was observed with 0.1 mmol/L H2O2
      or with 0.05 mmol/L menadione. Induction was detectable after 12 hours, reached a
      climax at 18 hours, and then decreased. Pretreatment of the cells with
      pyrrolidine dithiocarbamate completely abolished PAP-I mRNA induction, suggesting
      involvement of NFkappaB in the signaling pathway. These findings were confirmed
      in transient transfection assays using a plasmid containing the PAP-I promoter
      linked to the chloramphenicol acetyltransferase reporter gene. Then the
      relationship between PAP-I induction and protection against cell damage during
      oxidative stress was considered. Constitutive PAP-I expression in AR4-2J cells
      after transfection with PAP-I complementary DNA conferred significant resistance
      to apoptosis induced by low doses of H2O2 but not to necrosis induced by high
      doses of H2O2. CONCLUSIONS: These results suggest that during oxidative stress,
      PAP-I might be part of a mechanism of pancreatic cell protection against
      apoptosis.

PMID- 9516403
TI  - Octreotide suppression test predicts beneficial outcome from antrectomy in a
      patient with gastric carcinoid tumor.
AB  - Multiple gastric carcinoids are a well-recognized complication of
      hypergastrinemia associated with chronic atrophic gastritis. However, the
      management of large tumors (>2 cm in diameter) remains uncertain, with the
      decision between antrectomy or total gastrectomy being empirical. This report
      describes the investigation of a patient with chronic atrophic gastritis and
      multiple large gastric carcinoid tumors. Before surgery, octreotide was infused
      for 72 hours to suppress enterochromaffin-like (ECL) cell and gastrin cell
      function. The infusion decreased plasma gastrin and gastrin synthesis; moreover,
      there were marked reductions in markers of ECL cell function, e.g., histidine
      decarboxylase and chromogranin A messenger RNA abundance, in carcinoid tumor
      tissue and macroscopically normal corpus mucosa. An antrectomy was performed,
      after which the patient made an uneventful recovery. Six months after surgery, a
      single residual polyp, enriched with smooth muscle cells but not ECL cells, was
      removed. One year after antrectomy, the remaining stomach was normal. The
      response of ECL cell markers in carcinoid tissue to octreotide suggested that
      these cells were under neuroendocrine control and, therefore, predicted a
      beneficial outcome for antrectomy. It is suggested that an octreotide supression
      test coupled with assay of histidine decarboxylase or chromogranin A gene
      expression is useful in the assessment of gastric carcinoid tumors.

PMID- 9516404
TI  - Neural emergency system in the stomach.
AB  - The maintenance of gastric mucosal integrity depends on the rapid alarm of
      protective mechanisms in the face of pending injury. Afferent neurons of
      extrinsic origin constitute an emergency system that is called into operation
      when the gastric mucosa is endangered by acid and other noxious chemicals. The
      function of these chemoceptive afferents can be manipulated selectively and
      explored with the excitotoxin capsaicin. Most of the homeostatic actions of
      capsaicin-sensitive afferents are brought about by peptides released from their
      peripheral endings in the gastric wall. When stimulated, chemoceptive afferents
      enhance gastric blood flow and activate hyperemia-dependent and hyperemia
      independent mechanisms of protection and repair. In the rodent stomach, these
      local regulatory roles of sensory neurons are mediated by calcitonin gene-related
      peptide acting via calcitonin gene-related peptide 1 receptors and neurokinin A
      acting via neurokinin 2 receptors, with both peptides using nitric oxide as their
      common messenger. In addition, capsaicin-sensitive neurons form the afferent arc
      of autonomic reflexes that control secretory and motor functions of the stomach.
      The pathophysiological potential of the neural emergency system is best portrayed
      by the gastric hyperemic response to acid backdiffusion, which is signaled by
      afferent nerve fibers. This mechanism limits damage to the surface of the mucosa
      and creates favorable conditions for rapid restitution and healing of the wounded
      mucosa.

PMID- 9516405
TI  - Organization of HIV-1 capsid proteins on a lipid monolayer.
AB  - In an in vitro system that mimics the assembly of immature human immunodeficiency
      virus (HIV) particles, ordered arrays of HIV-1 capsid (CA) proteins encoded by
      the viral gag gene have been obtained by incubation of histidine-tagged capsid
      proteins (His-HIVCA) beneath lipid monolayers containing the nickel-chelating
      lipid, 1,2-di-O-hexadecyl-sn-glycero-3-(1'-2"-R-hydroxy-3'-N-(5-amino-1-
      carboxypentyl)iminodiacetic acid)propyl ether. The membrane-bound His-HIVCA
      proteins formed small crystalline arrays of primitive (p1) unit cells with
      dimensions of a = 74.2 A, b = 126.2 A, gamma = 89.3 degrees. The image-analyzed
      two-dimensional projection of His-HIVCA assemblies shows a cage-like lattice,
      consisting of hexamer and trimer units, surrounding protein-free cage holes. The
      hexamer-coordinated cage holes of 26.3-A diameter are spaced at 74. 2-A
      intervals: these distances, and the hexamer-trimer arrangement, are consistent
      with previous, lower resolution studies on immature HIV-1 virus particles
      produced in vivo. Additionally, HIV-1 matrix protein trimer unit structures align
      to the His-HIVCA trimer units such that residues previously shown to interact
      with the HIV-1 gp120/gp41 envelope protein complex are oriented toward the
      hexamer cage holes. Our results form a bridge between results from conventional
      methods for the analysis of HIV particle structure.

PMID- 9516406
TI  - Regulation of the phosphorylation state of rhodopsin by dopamine.
AB  - G protein-coupled receptors (GPCRs) are regulated by kinases and phosphatases
      that control their phosphorylation state. Here, the possibility that the state of
      GPCR phosphorylation could be affected by paracrine input was explored. We show
      that dopamine increased the rate of dephosphorylation of rhodopsin, the light
      receptor, in intact frog retinas. Further, we found that rod outer segments from
      dopamine-treated retinas contained increased rhodopsin phosphatase activity,
      indicating that this effect of dopamine on rhodopsin was mediated by stimulation
      of rhodopsin phosphatase. Dopamine is a ubiquitous neuromodulator and, in the
      retina, is released from the inner cell layers. Thus, our results identify a
      pathway for feedback regulation of rhodopsin from the inner retina and illustrate
      the involvement of dopamine in paracrine regulation of the sensitivity of a GPCR.

PMID- 9516407
TI  - Inhibition of Alzheimer beta-fibrillogenesis by melatonin.
AB  - It is generally postulated that the amyloid beta protein (Abeta) plays a central
      role in the progressive neurodegeneration observed in Alzheimer's disease.
      Important pathologic properties of this protein, such as neurotoxicity and
      resistance to proteolytic degradation, depend on the ability of Abeta to form
      beta-sheet structures or amyloid fibrils. We report that melatonin, a hormone
      recently found to protect neurons against Abeta toxicity, interacts with Abeta1
      40 and Abeta1-42 and inhibits the progressive formation of beta-sheets and
      amyloid fibrils. These interactions between melatonin and the amyloid peptides
      were demonstrated by circular dichroism and electron microscopy for Abeta1-40 and
      Abeta1-42 and by nuclear magnetic resonance spectroscopy for Abeta1-40.
      Inhibition of beta-sheets and fibrils could not be accomplished in control
      experiments when a free radical scavenger or a melatonin analog were substituted
      for melatonin under otherwise identical conditions. In sharp contrast with
      conventional anti-oxidants and available anti-amyloidogenic compounds, melatonin
      crosses the blood-brain barrier, is relatively devoid of toxicity, and
      constitutes a potential new therapeutic agent in Alzheimer's disease.

PMID- 9516408
TI  - Cotranslational ubiquitination of cystic fibrosis transmembrane conductance
      regulator in vitro.
AB  - Ubiquitination is a covalent protein modification that can target proteins in
      eukaryotic cells for degradation by the 26 S proteasome. Substrates for this
      degradation pathway include abnormal proteins that arise from misfolding and/or
      mutation. How and when the ubiquitination machinery recognizes misfolded proteins
      and targets them for degradation remains largely unknown. We have previously
      shown that cystic fibrosis transmembrane conductance regulator (CFTR), is rapidly
      degraded in a ubiquitin-dependent fashion, without any detectable lag following
      its synthesis (Ward, C. L., and Kopito, R. R. (1994) J. Biol. Chem. 269, 25710
      25718), suggesting that ubiquitination and protein synthesis may be temporally
      linked. In the present study, we have investigated the timing of CFTR
      ubiquitination relative to its translation in reticulocyte lysates containing
      125I-ubiquitin. In synchronized, proteasome-inhibited lysates, translation of
      full-length CFTR chains was completed in approximately 30 min, whereas
      modification of CFTR with [125I]ubiquitin was evident by 20 min, indicating that
      ubiquitination precedes the completion of full-length polypeptide chains.
      Moreover, ubiquitin was also found to be transferred to nascent CFTR chains while
      attached to ribosomes. Together, these data establish that ubiquitination, which
      is widely assumed to be a post-translational event, can occur cotranslationally
      and suggest a role for ubiquitination early in protein biosynthesis.

PMID- 9516409
TI  - Protein components contribute to active site architecture for eukaryotic
      ribonuclease P.
AB  - In eukaryotes, ribonuclease P (RNase P) requires both RNA and protein components
      for catalytic activity. The eukaryotic RNase P RNA, unlike its bacterial
      counterparts, does not possess intrinsic catalytic activity in the absence of
      holoenzyme protein components. We have used a sensitive photoreactive cross
      linking assay to explore the substrate-binding environment for different
      eukaryotic RNase P holoenzymes. Protein components from the Tetrahymena
      thermophila and human RNase P holoenzymes form specific products in
      photoreactions containing [4-thio]-uridine-labeled pre-tRNAGln. The HeLa RNase P
      RNA in neither the presence nor the absence of holoenzyme protein components
      formed cross-link products to the pre-tRNAGln probe. Parallel photo-cross-linking
      experiments with the Escherichia coli RNase P holoenzyme revealed that only the
      bacterial RNase P RNA forms specific substrate photoadducts. A protein-rich
      active site for the eukaryotic RNase P represents one unique feature that
      distinguishes holoenzyme organization between bacteria and eukaryotes.

PMID- 9516410
TI  - Receptor docking sites for G-protein betagamma subunits. Implications for signal
      regulation.
AB  - We report the direct interaction of Gbetagamma with the third intracellular (i3)
      loop of the M2- and M3-muscarinic receptors (MR) and the importance of this
      interaction relative to effective phosphorylation of the receptor subdomain. The
      i3 loop of the M2- and the M3-MR were expressed in bacteria and purified as
      glutathione S-transferase fusion proteins for utilization as an affinity matrix
      and to generate substrate for receptor subdomain phosphorylation. In its inactive
      heterotrimeric state stabilized by GDP, brain G-protein did not associate with
      the i3 peptide affinity matrix. However, stimulation of subunit dissociation by
      GTPgammaS/Mg2+ resulted in the retention of Gbetagamma, but not the Galpha
      subunit, by the M2- and M3-MR i3 peptide resin. Purified Gbetagamma bound to the
      M3-MR i3 peptide with an apparent affinity similar to that observed for the
      Gbetagamma binding domain of the receptor kinase GRK2 and Bruton tyrosine kinase,
      whereas transducin betagamma was not recognized by the M3-MR i3 peptide.
      Effective phosphorylation of the M3-MR peptide by GRK2 required both Gbetagamma
      and lipid as is the case for the intact receptor. Incubation of purified GRK2
      with the i3 peptide in the presence of Gbetagamma resulted in the formation of a
      functional ternary complex in which Gbetagamma served as an adapter protein. Such
      a complex provides a mechanism for specific spatial translocation of GRK2 within
      the cell positioning the enzyme on its substrate, the activated receptor. The
      apparent ability of Gbetagamma to act as a docking protein may also serve to
      provide an interface for this class of membrane-bound receptors to an expanded
      array of signaling pathways.

PMID- 9516411
TI  - Insulin increases the association of Akt-2 with Glut4-containing vesicles.
AB  - Expression of a constitutively active, membrane-associated Akt-1 (PKB alpha)
      construct in 3T3L1 adipocytes was shown to induce glucose uptake in the absence
      of insulin by stimulating Glut4 translocation to the plasma membrane (Kohn, A.
      D., Summers, S. A., Birnbaum, M. J., and Roth, R. A. (1996) J. Biol. Chem. 271,
      31372-31378). However, in rat fat cell the vast majority of Akt-1 is cytosolic
      and shows no re-distribution to the plasma membrane in response to insulin. On
      the other hand, little work has been done with other Akt family members such as
      Akt-2 (PKB beta) or Akt-3 (PKB gamma). In this report, an analysis of the
      subcellular distribution of Akt-2 in rat adipocytes shows that Akt-2 is present
      in significant amounts in various membrane compartments, as well as in the
      cytosol, and the former include the light microsomes where Glut4 is present in
      the basal state. The distribution of Akt-2 in resting adipocytes was found to
      substantially overlap with that of Glut4 when light microsomes were
      subfractionated by a sucrose velocity gradient indicating possible co
      localization. We confirmed co-localization of Akt-2 and Glut4 in the basal state
      by immunopurification of Glut4 vesicles, which exhibited a 5.5-fold increase in
      Akt-2 in response to insulin relative to the amount of Glut4. These results are
      consistent with the possibility that Akt-2 may be involved in Glut4 vesicle
      translocation.

PMID- 9516412
TI  - Involvement of dihydropyridine-sensitive calcium channels in human dendritic cell
      function. Competition by HIV-1 Tat.
AB  - The entry of extracellular calcium in leukocytes mediates several cellular
      processes; however, unlike in excitable tissues, the underlying molecular
      mechanisms are poorly defined. In this paper we provide phenotypical and
      biochemical evidence that peripheral blood-derived human dendritic cells express
      dihydropyridine-sensitive calcium channels. Exposure to the dihydropyridine drug
      nifedipine, which binds L-type calcium channels blocking calcium influx, prevents
      two dendritic cell functions that are dependent on extracellular calcium entry:
      apoptotic body engulfment and interleukin-12 production induced by cross-linking
      of the surface lectin NKRP1A. It is known that exogenous human immunodeficiency
      virus, type 1 Tat affects several Ca2+-dependent immune cell responses. Here we
      demonstrate that Tat inhibits apoptotic body engulfment and interleukin-12
      production by blocking extracellular calcium influx. This inhibition is prevented
      by the calcium channel agonist dihydropyridine derivative Bay K 8644, suggesting
      the involvement of L-type calcium channels. This hypothesis is further supported
      by the observation that Tat and dihydropyridine drugs compete for binding to
      dendritic cells. Taken together, these findings indicate that exogenous Tat
      exerts its inhibitory effects on dendritic cells by blocking dihydropyridine
      sensitive L-type calcium channels.

PMID- 9516413
TI  - Dissection of the transactivation function of the transcription factor encoded by
      the eye developmental gene PAX6.
AB  - PAX6 is a transcription activator that regulates eye development in animals
      ranging from Drosophila to human. The C-terminal region of PAX6 is
      proline/serine/threonine-rich (PST) and functions as a potent transactivation
      domain when attached to a heterologous DNA-binding domain of the yeast
      transcription factor, GAL4. The PST region comprises 152 amino acids encoded by
      four exons. The transactivation function of the PST region has not been defined
      and characterized in detail by in vitro mutagenesis. We dissected the PST domain
      in two independent systems, a heterologous system using a GAL4 DNA-binding site
      and the native system of PAX6. Our data consistently showed that in both systems
      all four constituent exons of the PST domain are responsible for the
      transactivation function. The four exon fragments act synergistically to
      stimulate transcription, although none of them can function individually as an
      independent transactivation domain. Combinations of two or more exon fragments
      can reconstitute substantial transactivation activity when fused to the DNA
      binding domain of GAL4, but they surprisingly do not produce much activity in the
      context of native PAX6, although the mutant PAX6 proteins are stable and their
      DNA-binding function remains unaffected. Our data suggest that these mutants may
      antagonize the wild-type PAX6 activity by competing for target DNA-binding sites.
      We conclude that the PAX6 protein contains an unusually large transactivation
      domain that is evolutionarily conserved to a high degree and that its full
      transactivation activity relies on the synergistic action of the four exon
      fragments.

PMID- 9516414
TI  - Amino-terminal truncation of chemokines by CD26/dipeptidyl-peptidase IV.
      Conversion of RANTES into a potent inhibitor of monocyte chemotaxis and HIV-1
      infection.
AB  - Chemokines are key players in inflammation and infection. Natural forms of the C
      X-C chemokine granulocyte chemotactic protein-2 (GCP-2) and the C-C chemokine
      regulated on activation normal T cell expressed and secreted (RANTES), which miss
      two NH2-terminal residues, including a Pro in the penultimate position, have been
      isolated from leukocytes or tumor cells. In chemotaxis and intracellular calcium
      mobilization assays, the truncation caused a reduction in the specific activity
      of RANTES but not of GCP-2. The serine protease CD26/dipeptidyl-peptidase IV
      (CD26/DPP IV) could induce this observed NH2-terminal truncation of GCP-2 and
      RANTES but not that of the monocyte chemotactic proteins MCP-1, MCP-2 and MCP-3.
      No significant difference in neutrophil activation was detected between intact
      and CD26/DPP IV-truncated GCP-2. In contrast to intact natural RANTES(1-68),
      which still chemoattracts monocytes at 10 ng/ml, CD26/DPP IV-truncated RANTES(3
      68) was inactive at 300 ng/ml and behaved as a natural chemotaxis inhibitor.
      Compared with intact RANTES, only a 10-fold higher concentration of RANTES(3-68)
      induced a significant Ca2+ response. Furthermore, RANTES(3-68) inhibited
      infection of mononuclear cells by an M-tropic HIV-1 strain 5-fold more
      efficiently than intact RANTES. Thus, proteolytic processing of RANTES by
      CD26/DPP IV may constitute an important regulatory mechanism during anti
      inflammatory and antiviral responses.

PMID- 9516415
TI  - Stimulation of "stress-regulated" mitogen-activated protein kinases (stress
      activated protein kinases/c-Jun N-terminal kinases and p38-mitogen-activated
      protein kinases) in perfused rat hearts by oxidative and other stresses.
AB  - "Stress-regulated" mitogen-activated protein kinases (SR-MAPKs) comprise the
      stress-activated protein kinases (SAPKs)/c-Jun N-terminal kinases (JNKs) and the
      p38-MAPKs. In the perfused heart, ischemia/reperfusion activates SR-MAPKs.
      Although the agent(s) directly responsible is unclear, reactive oxygen species
      are generated during ischemia/reperfusion. We have assessed the ability of
      oxidative stress (as exemplified by H2O2) to activate SR-MAPKs in the perfused
      heart and compared it with the effect of ischemia/reperfusion. H2O2 activated
      both SAPKs/JNKs and p38-MAPK. Maximal activation by H2O2 in both cases was
      observed at 0.5 mM. Whereas activation of p38-MAPK by H2O2 was comparable to that
      of ischemia and ischemia/reperfusion, activation of the SAPKs/JNKs was less than
      that of ischemia/reperfusion. As with ischemia/reperfusion, there was minimal
      activation of the ERK MAPK subfamily by H2O2. MAPK-activated protein kinase 2
      (MAPKAPK2), a downstream substrate of p38-MAPKs, was activated by H2O2 to a
      similar extent as with ischemia or ischemia/reperfusion. In all instances,
      activation of MAPKAPK2 in perfused hearts was inhibited by SB203580, an inhibitor
      of p38-MAPKs. Perfusion of hearts at high aortic pressure (20 kilopascals) also
      activated the SR-MAPKs and MAPKAPK2. Free radical trapping agents (dimethyl
      sulfoxide and N-t-butyl-alpha-phenyl nitrone) inhibited the activation of SR
      MAPKs and MAPKAPK2 by ischemia/reperfusion. These data are consistent with a role
      for reactive oxygen species in the activation of SR-MAPKs during
      ischemia/reperfusion.

PMID- 9516416
TI  - Heat-induced elevation of ceramide in Saccharomyces cerevisiae via de novo
      synthesis.
AB  - Sphingolipid-related metabolites have been implicated as potential signaling
      molecules in many studies with mammalian cells as well as in some studies with
      yeast. Our previous work showed that sphingolipid-deficient strains of
      Saccharomyces cerevisiae are unable to resist a heat shock, indicating that
      sphingolipids are necessary for surviving heat stress. Recent evidence suggests
      that one role for the sphingolipid intermediate ceramide may be to act as a
      second messenger to signal accumulation of the thermoprotectant trehalose. We
      examine here the mechanism for generating the severalfold increase in ceramide
      observed during heat shock. As judged by compositional analysis and mass
      spectrometry, the major ceramides produced during heat shock are similar to those
      found in complex sphingolipids, a mixture of N-hydroxyhexacosanoyl C18 and C20
      phytosphingosines. Since the most studied mechanism for ceramide generation in
      animal cells is via a phospholipase C-type sphingomyelin hydrolysis, we examined
      S. cerevisiae for an analogous enzyme. Using [3H]phytosphingosine and
      [3H]inositol-labeled yeast sphingolipids, a novel membrane-associated
      phospholipase C-type activity that generated ceramide from inositol-P-ceramide,
      mannosylinositol-P-ceramide, and mannose(inositol-P)2-ceramide was demonstrated.
      The sphingolipid head groups were concomitantly liberated with the expected
      stoichiometry. However, other data demonstrate that the ceramide generated during
      heat shock is not likely to be derived by breakdown of complex sphingolipids. For
      example, the water-soluble fraction of heat-shocked cells showed no increase in
      any of the sphingolipid head groups, which is inconsistent with complex
      sphingolipid hydrolysis. Rather, we find that de novo ceramide synthesis
      involving ceramide synthase appears to be responsible for heat-induced ceramide
      elevation. In support of this hypothesis, we find that the potent ceramide
      synthase inhibitor, australifungin, completely inhibits both the heat-induced
      increase in incorporation of [3H]sphinganine into ceramide as well as the heat
      induced increase in ceramide as measured by mass. Thus, heat-induced ceramide
      most likely arises by temperature activation of the enzymes that generate
      ceramide precursors, activation of ceramide synthase itself, or both.

PMID- 9516417
TI  - Functional analysis of disulfide linkages clustered within the amino terminus of
      human apolipoprotein B.
AB  - We tested the involvement of N-terminal six disulfide bonds (Cys-1 through Cys
      12) of human apolipoprotein (apo) B in the assembly and secretion of lipoproteins
      using two C-terminal-truncated apoB variants, namely B50 and B18. In transfected
      rat hepatoma McA-RH7777 cells, B50 could assemble very low density lipoproteins
      (VLDL), and B18 was secreted as high density lipoproteins. When all 12 cysteine
      residues were substituted with alanines in B50, the mutant protein (B50C1-12)
      lost its ability to assemble lipid and was degraded intracellularly. However,
      mutation had no effect on B50C1-12 translation or translocation across the
      microsomal membrane. Post-translational degradation of B50C1-12 was partially
      inhibited by the proteasome inhibitor MG132. To determine which cysteines were
      critical in VLDL assembly and secretion, we prepared three additional mutant
      B50s, each containing four selected Cys-to-Ala substitutions in tandem (i.e. Cys
      1 to Cys-4, Cys-5 to Cys-8, and Cys-9 to Cys-12). Expression of these mutants
      showed that disruption of disulfide bond formation within Cys-5 to Cys-8
      diminished apoB secretion, whereas within Cys-1 to Cys-4 or Cys-9 to Cys-12 had
      lesser or no effect. In another two mutants in which only one disulfide bond
      (i.e. between Cys-5 and Cys-6 or between Cys-7 and Cys-8) was eliminated, only
      secretion of B50 with mutations at Cys-7 and Cys-8 was decreased. Thus, the
      disulfide bond involving Cys-7 and Cys-8 is most important for VLDL assembly and
      secretion. In addition, assembly and secretion of VLDL containing endogenous B100
      or B48 were impaired in cells transfected with B50s containing Cys-7 and Cys-8
      mutation. The Cys-to-Ala substitution abolished recognition of B50 by MB19, a
      conformational antibody with an epitope at the N terminus of human apoB. The Cys
      to-Ala substitution also attenuated secretion of B18, but the effect of the
      mutation on B18 secretion was less evident than on B50.

PMID- 9516418
TI  - A peptide derived from a conserved domain of Sendai virus fusion protein inhibits
      virus-cell fusion. A plausible mode of action.
AB  - SV-201, a peptide derived from a conserved and potentially amphipathic region
      (amino acids 201-229) in the Sendai virus ectodomain, specifically inhibited
      virus-mediated hemolysis only when added to virions prior to their attachment to
      red blood cells. Sendai virus-mediated hemagglutinin assay in the presence of SV
      201 demonstrated that the peptide does not disturb the binding of virions to the
      target red blood cells. A mutated peptide with 2 amino acids substitution,
      rendering the peptide neutral, was biologically inactive. A second mutant with 7
      amino acids randomized at the N terminus keeping the hydrophobicity of the
      peptide unaltered was only slightly active. A hydrophobic peptide corresponding
      to the fusion peptide domain was also inactive. SV-201, the two mutants, and the
      fusion peptide bind similarly with high affinity to both negatively charged
      phosphatidylserine/phosphatidylcholine and zwitterionic phosphatidylcholine lipid
      vesicles, suggesting that the inhibitory effect is not due merely to membrane
      modulation. Fluorescence studies with rhodamine-labeled peptides and SV-201
      induced inhibition assays, demonstrated that the SV-201 binding site is most
      probably located in the region corresponding to amino acids 201-229 of the Sendai
      virus fusion protein. The data presented here suggest that SV-201 disturbs a
      functional domain in the Sendai virus fusion protein, which is most probably
      associated with the assembly of the fusion protein and/or membrane apposition.
      The existence of homologous SV-201 regions in other viruses suggests that these
      regions may have a similar role, and their synthetic counterparts may act as
      inhibitors for the corresponding viruses.

PMID- 9516419
TI  - Cloning, expression in yeast, and functional characterization of CYP81B1, a plant
      cytochrome P450 that catalyzes in-chain hydroxylation of fatty acids.
AB  - Several omega and in-chain fatty acid hydroxylases have been characterized in
      higher plants. In microsomes from Helianthus tuberosus tuber the omega-2, omega
      3, and omega-4 hydroxylation of lauric acid is catalyzed by one or a few closely
      related aminopyrine- and MnCl2-inducible cytochrome P450(s). To isolate the cDNA
      and determine the sequences of the(se) enzyme(s), we used antibodies directed
      against a P450-enriched fraction purified from Mn2+-induced tissues. Screening of
      a cDNA expression library from aminopyrine-treated tubers led to the
      identification of a cDNA (CYP81B1) corresponding to a transcript induced by
      aminopyrine. CYP81B1 was expressed in yeast. A systematic exploration of its
      function revealed that it specifically catalyzes the hydroxylation of medium
      chain saturated fatty acids, capric (C10:0), lauric (C12:0), and myristic (C14:0)
      acids. The same metabolites were obtained with transgenic yeast and plant
      microsomes, a mixture of omega-1 to omega-5 monohydroxylated products. The three
      fatty acids were metabolized with high and similar efficiencies, the major
      position of attack depending on chain length. When lauric acid was the substrate,
      turnover was 30.7 +/- 1.4 min-1 and Km(app) 788 +/- 400 nM. No metabolism of long
      chain fatty acids, aromatic molecules, or herbicides was detected. This new fatty
      acid hydroxylase is typical from higher plants and differs from those already
      isolated from other living organisms.

PMID- 9516420
TI  - The biochemical and phenotypic characterization of Hho1p, the putative linker
      histone H1 of Saccharomyces cerevisiae.
AB  - There is currently no published report on the isolation and definitive
      identification of histone H1 in Saccharomyces cerevisiae. It was, however,
      recently shown that the yeast HHO1 gene codes for a predicted protein homologous
      to H1 of higher eukaryotes (Landsman, D. (1996) Trends Biochem. Sci. 21, 287-288;
      Ushinsky, S. C., Bussey, H. , Ahmed, A. A., Wang, Y., Friesen, J., Williams, B.
      A., and Storms, R. K. (1997) Yeast 13, 151-161), although there is no biochemical
      evidence that shows that Hho1p is, indeed, yeast histone H1. We showed that
      purified recombinant Hho1p (rHho1p) has electrophoretic and chromatographic
      properties similar to linker histones. The protein forms a stable ternary complex
      with a reconstituted core di-nucleosome in vitro at molar rHho1p:core ratios up
      to 1. Reconstitution of rHho1p with H1-stripped chromatin confers a kinetic pause
      at approximately 168 base pairs in the micrococcal nuclease digestion pattern of
      the chromatin. These results strongly suggest that Hho1p is a bona fide linker
      histone. We deleted the HHO1 gene and showed that the strain is viable and has no
      growth or mating defects. Hho1p is not required for telomeric silencing, basal
      transcriptional repression, or efficient sporulation. Unlike core histone
      mutations, a hho1Delta strain does not exhibit a Sin or Spt phenotype. The
      absence of Hho1p does not lead to a change in the nucleosome repeat length of
      bulk chromatin nor to differences in the in vivo micrococcal nuclease cleavage
      sites in individual genes as detected by primer extension mapping.

PMID- 9516421
TI  - Transcriptional analysis of the EhPgp1 promoter of Entamoeba histolytica
      multidrug-resistant mutant.
AB  - We present here the cloning and characterization of the EhPgp1 multidrug
      resistance gene promoter isolated from the Entamoeba histolytica drug-resistant
      mutant clone C2. The EhPgp1 promoter lacks the typical TATA box and the
      transcriptional initiation sequences described for other E. histolytica
      promoters. The major transcription initiation site of the EhPgp1 gene was located
      at the ATG start codon. The EhPgp1 core promoter located within the first 244
      base pairs showed a higher chloramphenicol acetyltransferase expression in the
      transfected trophozoites of clone C2 than in those of the sensitive clone A. Gel
      shift assays revealed three specific DNA-protein complexes (Ia, IIa, and IIIc)
      using nuclear extracts from clone C2, whereas three main complexes (If, IIf, and
      IIg) were limited to clone A. Competition assays suggested the presence of C/EBP
      like and OCT-like proteins in complexes Ia and IIa, respectively, probably
      involved in the expression of the EhPgp1 gene, whereas complex IIIc was competed
      by GATA-1, C/EBP, OCT, and HOX oligonucleotides. Thus, differential DNA-protein
      complexes may be formed by transcriptional factors involved in the regulation of
      the EhPgp1 gene expression.

PMID- 9516422
TI  - Transcriptional analysis of the EhPgp5 promoter of Entamoeba histolytica
      multidrug-resistant mutant.
AB  - We report here the cloning and transcriptional characterization of the EhPgp5
      multidrug resistance gene promoter isolated from the drug-resistant clone C2 of
      Entamoeba histolytica. The EhPgp5 promoter has the TATA-like motif at -31 base
      pairs; transcription initiates three nucleotides upstream from the ATG in
      trophozoites grown in 225 microM emetine (clone C2(225)), whereas in those grown
      without the drug (clone C2) a product with no open reading frame was detected.
      The promoter was active in transfected clone C2 trophozoites, its activity
      increased when trophozoites were cultured in 40 microM emetine, while it was
      turned off in the drug-sensitive clone A. The first -235 base pair kept full
      promoter activity, suggesting that it has important drug responsive elements. Gel
      shift assays detected the complex Ib in clone C2, which was augmented in clone
      C2(225). Competition experiments suggested that complex Ib may be constituted by
      HOX and AP-1 like factors in clone C2, whereas in clone C2(225), complex Ib was
      only competed by the HOX sequence. Complexes Ie, detected in clones A and C2 but
      not in C2(225), and Ia, present in all clones, were competed by the TATA box
      oligonucleotide. Our results suggest that proteins forming complexes Ib and Ie
      may be participating in the regulation of the EhPgp5 gene expression.

PMID- 9516423
TI  - Cloning and expression of mouse liver phosphatidylserine synthase-1 cDNA.
      Overexpression in rat hepatoma cells inhibits the CDP-ethanolamine pathway for
      phosphatidylethanolamine biosynthesis.
AB  - In eukaryotic cells, phosphatidylserine (PtdSer) is synthesized by two distinct
      synthases on the endoplasmic reticulum by a base-exchange reaction in which the
      polar head-group of an existing phospholipid is replaced with serine. We report
      the cloning and expression of a cDNA for mouse liver PtdSer synthase-1. The
      deduced protein sequence is >90% identical to that of PtdSer synthase-1 from
      Chinese hamster ovary cells and a sequence from a human myeloblast cell line.
      PtdSer synthase-1 cDNA was stably expressed in M.9.1.1 cells which are mutant
      Chinese hamster ovary cells defective in PtdSer synthase-1 activity, are
      ethanolamine auxotrophs, and have a reduced content of PtdSer and
      phosphatidylethanolamine (PtdEtn). The growth defect of M.9.1.1 cells was
      eliminated, and a normal phospholipid composition was restored in the absence of
      exogenous ethanolamine, implying that the cloned cDNA encoded PtdSer synthase.
      Mouse liver PtdSer synthase-1 was also expressed in McArdle 7777 rat hepatoma
      cells. In addition to a 3-fold higher in vitro serine-exchange activity, these
      cells also exhibited enhanced choline- and ethanolamine-exchange activities and
      incorporated more [3H]serine into PtdSer than did control cells. However, the
      levels of PtdSer and PtdEtn in cells overexpressing PtdSer synthase-1 activity
      were not increased. Excess PtdSer produced by the transfected cells was rapidly
      decarboxylated to PtdEtn and the degradation of PtdSer, and/or PtdEtn derived
      from PtdSer, was increased. Moreover, the CDP-ethanolamine pathway for PtdEtn
      biosynthesis was inhibited. These data suggest that (i) cellular levels of PtdSer
      and PtdEtn are tightly controlled, and (ii) the metabolism of PtdSer and PtdEtn
      is coordinately regulated to maintain phospholipid homeostasis.

PMID- 9516424
TI  - Interaction of heparan sulfate from mammary cells with acidic fibroblast growth
      factor (FGF) and basic FGF. Regulation of the activity of basic FGF by high and
      low affinity binding sites in heparan sulfate.
AB  - We have determined the relationship between the binding sites for acidic
      fibroblast growth factor (aFGF) and basic FGF (bFGF) in heparan sulfate (HS)
      prepared from a panel of mammary cell lines and the ability of the HS to activate
      aFGF and bFGF in DNA synthesis assays. The ka of the HS for aFGF fell into three
      groups, whereas the kd (0.0015-0.016 s-1) and the Kd (0.4-8.6 microM) formed a
      continuum. bFGF possessed a high affinity binding site (Kd 22-30 nM) with a fast
      ka (320,000-550,000 M-1 s-1), termed "fast/high," and a lower affinity site (Kd
      47-320 nM) with a slower ka (35,000-150,000 M-1 s-1), termed "slow/low." Most of
      the species of HS possessed the latter binding site, which was able to activate
      bFGF in HS-deficient fibroblasts. However, the HS from the culture medium of the
      mammary fibroblasts and the myoepithelial-like cells possessed both a fast/high
      and a slow/low binding site and could not activate bFGF, although it could
      potentiate the growth-stimulatory activity of aFGF. Treatment of the HS
      possessing two binding sites for bFGF with heparitinase 1 released
      oligosaccharides that were able to restore the activity of bFGF in HS-deficient
      fibroblasts.

PMID- 9516425
TI  - Interactions between fragments of trypsinized Na,K-ATPase detected by thermal
      inactivation of Rb+ occlusion and dissociation of the M5/M6 fragment.
AB  - This work provides evidence for interactions between fragments of "19-kDa
      membranes," a trypsinized preparation of Na,K-ATPase that retains cation
      occlusion and ouabain binding. Previously, we reported rapid thermal inactivation
      of Rb+ occlusion at 37 degreesC (Or, E., David, P., Shainskaya, A., Tal, D. M.,
      and Karlish, S. J. D. (1993) J. Biol. Chem. 268, 16929-16937). We describe here
      the detailed kinetics of thermal inactivation. In the range 25-35 degreesC, a two
      step model (N left and right arrow U --> I, where N is the native species, U is
      the reversibly unfolded intermediate, and I is the irreversibly denatured form)
      fits the data. Reversibility of inactivation has been observed at 25 degreesC,
      consistent with the model. At 37 degreesC and higher temperatures, the data can
      be fitted to the simple mechanism N --> I, i.e. U is not significant as an
      intermediate. Occluded cations (Na+, Rb+, K+, Tl+, NH4+, and Cs+) and ouabain
      protect strongly against thermal inactivation. Ca2+, Ba2+, and La3+ ions do not
      protect. Proteolysis experiments provide independent evidence that
      disorganization can occur in stages, first in transmembrane segments and then in
      extra-membrane segments of the fragments. Analysis of selective dissociation of
      the M5/M6 fragment at 37 degreesC (Lutsenko, S., and Kaplan, J. H. (1995) Proc.
      Natl. Acad. Sci. U. S. A. 92, 7936-7940), using a specific antibody, showed that
      inactivation of Rb+ occlusion precedes dissociation of the fragment, and only
      approximately 50% of the fragment is released when occlusion is fully
      inactivated. In the presence of Ca2+ ions, occlusion is inactivated, but the
      M5/M6 fragment is not released. The experiments demonstrate that occlusion is
      inactivated by disruption of interactions between fragments of 19-kDa membranes,
      and only then does the M5/M6 fragment dissociate. Interactions between the M5/M6
      and M7/M10 fragments seem to be essential for maintenance of Rb+ occlusion.

PMID- 9516426
TI  - Human protein MCM6 on HeLa cell chromatin.
AB  - Minichromosome maintenance (Mcm) proteins perform essential functions regulating
      the replication of chromatin. Human cells, like other eukaryotic cells, express
      at least six Mcm proteins conserved in the central region. We have earlier
      described the primary structures of five human Mcm proteins, but the primary
      structure of the sixth human Mcm protein, MCM6, was identified only recently. We
      now use antibodies, specific for the MCM6 protein, to assess its intranuclear
      distribution. We find that a fraction of MCM6 protein occurs in the nucleosol,
      forming multiprotein complexes with other Mcm proteins. More importantly, we use
      for the first time micrococcal nuclease as a tool to investigate the association
      of MCM6 protein with chromatin. After short digestion times, a considerable
      fraction of the MCM6 protein is released from chromatin as a multiprotein complex
      that includes other Mcm proteins as well. In addition, fractions of MCM3 and MCM6
      proteins are released by nuclease digestion as monomeric proteins indicating that
      at least these two Mcm proteins may also occur as single molecules on chromatin.
      The data also suggest that the chromatin regions with bound Mcm proteins are more
      vulnerable to nuclease attack than bulk chromatin and may therefore differ in the
      arrangement of nucleosomes.

PMID- 9516427
TI  - The chemorepulsive activity of the axonal guidance signal semaphorin D requires
      dimerization.
AB  - The axonal guidance signal semaphorin D is a member of a large family of proteins
      characterized by the presence of a highly conserved semaphorin domain of about
      500 amino acids. The vertebrate semaphorins can be divided into four different
      classes that contain both secreted and membrane-bound proteins. Here we show that
      class III (SemD) and class IV semaphorins (SemB) form homodimers linked by
      intermolecular disulfide bridges. In addition to the 95-kDa form of SemD
      (SemD(95k)), proteolytic processing of SemD creates a 65-kDa isoform (SemD(65k))
      that lacks the 33-kDa carboxyl-terminal domain. Although SemD(95k) formed dimers,
      the removal of the carboxyl-terminal domain resulted in the dissociation of SemD
      homodimers to monomeric SemD(65k). Mutation of cysteine 723, one of four
      conserved cysteine residues in the 33-kDa fragment, revealed its requirement both
      for the dimerization of SemD and its chemorepulsive activity. We suggest that
      dimerization is a general feature of sema- phorins which depends on class
      specific sequences and is important for their function.

PMID- 9516428
TI  - Pseudomonas aeruginosa exoenzyme S ADP-ribosylates Ras at multiple sites.
AB  - Pseudomonas aeruginosa exoenzyme S (ExoS) ADP-ribosylated Ras to a stoichiometry
      of approximately 2 molecules of ADP-ribose incorporated per molecule of Ras,
      which suggested that ExoS could ADP-ribosylate Ras at more than one arginine
      residue. SDS-polyacrylamide gel electrophoresis analysis showed that ADP
      ribosylated Ras possessed a slower mobility than non-ADP-ribosylated Ras.
      Analysis of the ADP-ribosylation of in vitro transcribed/translated Ras by ExoS
      identified two electrophoretically shifted forms of Ras, which was consistent
      with the ADP-ribosylation of Ras at two distinct arginine residues. Analysis of
      ADP-ribosylated in vitro transcribed/translated Ras mutants possessing individual
      Arg-to-Ala substitutions showed that Arg-41 was the preferred site of ADP
      ribosylation and that the second ADP-ribosylation event occurred at a slower rate
      than the ADP-ribosylation at Arg-41, but did not occur at a specific arginine
      residue. Analysis of bacterially expressed wild-type RasDeltaCAAX and
      RasDeltaCAAXR41K supported the conclusion that Arg-41 was the preferred site of
      ADP-ribosylation. Arg-41 is located adjacent to the switch 1 region of Ras, which
      is involved in effector interactions. Introduction of ExoS into eukaryotic cells
      inhibited Ras-mediated eukaryotic signal transduction since infection of PC-12
      cells with an ExoS-producing strain of P. aeruginosa inhibited nerve growth
      factor-stimulated neurite formation. This is the first demonstration that ExoS
      disrupts a Ras-mediated signal transduction pathway.

PMID- 9516430
TI  - Specific interaction of the recombinant disintegrin-like domain of MDC-15
      (metargidin, ADAM-15) with integrin alphavbeta3.
AB  - MDC-15 (ADAM-15, metargidin), a membrane-anchored
      metalloprotease/disintegrin/cysteine-rich protein, is expressed on the surface of
      a wide range of cells and has an RGD tripeptide in its disintegrin-like domain.
      MDC-15 is potentially involved in cell-cell interactions through its interaction
      with integrins. We expressed a recombinant MDC-15 disintegrin-like domain as a
      fusion protein with glutathione S-transferase (designated D-15) in bacteria and
      examined its binding function to integrins using mammalian cells expressing
      different recombinant integrins. We found that D-15 specifically interacts with
      alphavbeta3 but not with the other integrins tested (alpha2beta1, alpha3beta1,
      alpha4beta1, alpha5beta1, alpha6beta1, alpha6beta4, alphavbeta1, alphaIIbbeta3,
      and alphaLbeta2). Mutation of the tripeptide RGD to SGA totally blocked binding
      of D-15 to alphavbeta3, suggesting that D-15-alphavbeta3 interaction is RGD
      dependent. When the sequence RPTRGD is mutated to NWKRGD, D-15 is recognized by
      both alphaIIbbeta3 and alphavbeta3, suggesting that the receptor binding
      specificity is mediated by the sequence flanking the RGD tripeptide, as in snake
      venom disintegrins. These results indicate that the disintegrin-like domain of
      MDC-15 functions as an adhesion molecule and may be involved n alphavbeta3
      mediated cell-cell interactions.

PMID- 9516429
TI  - Substitutions of aspartate 378 in the phosphorylation domain of the yeast PMA1 H+
      ATPase disrupt protein folding and biogenesis.
AB  - There is strong evidence that Asp-378 of the yeast PMA1 ATPase plays an essential
      role in ATP hydrolysis by forming a covalent beta-aspartyl phosphate reaction
      intermediate. In this study, Asp-378 was replaced by Asn, Ser, and Glu, and the
      mutant ATPases were expressed in a temperature-sensitive secretion-deficient
      strain (sec6-4) that allowed their properties to be examined. Although all three
      mutant proteins were produced at nearly normal levels and remained stable for at
      least 2 h at 37 degrees C, they failed to travel to the vesicles that serve as
      immediate precursors of the plasma membrane; instead, they became arrested at an
      earlier step of the secretory pathway. A closer look at the mutant proteins
      revealed that they were firmly inserted into the bilayer and were not released by
      washing with high salt, urea, or sodium carbonate (pH 11), treatments commonly
      used to strip nonintegral proteins from membranes. However, all three mutant
      ATPases were extremely sensitive to digestion by trypsin, pointing to a marked
      abnormality in protein folding. Furthermore, in contrast to the wild-type enzyme,
      the mutant ATPases could not be protected against trypsinolysis by ligands such
      as MgATP, MgADP, or inorganic orthovanadate. Thus, Asp-378 functions in an
      unexpectedly complex way during the acquisition of a mature structure by the
      yeast PMA1 ATPase.

PMID- 9516431
TI  - Role of the GroEL chaperonin intermediate domain in coupling ATP hydrolysis to
      polypeptide release.
AB  - Modification of the Escherichia coli chaperonin GroEL with N-ethylmaleimide at
      residue Cys138 affects the structural and functional integrity of the complex.
      Nucleotide affinity and ATPase activity of the modified chaperonin are increased,
      whereas cooperativity of ATP hydrolysis and affinity for GroES are reduced. As a
      consequence, release and folding of substrate proteins are strongly impaired and
      uncoupled from ATP hydrolysis in a temperature-dependent manner. Folding of
      dihydrofolate reductase at 25 degrees C becomes dependent on GroES, whereas
      folding of typically GroES-dependent proteins is blocked completely. At 37
      degrees C, GroES binding is restored to normal levels, and the modified GroEL
      regains its chaperone activity to some extent. These results assign a central
      role to the intermediate GroEL domain for transmitting conformational changes
      between apical and central domains, and for coupling ATP hydrolysis to productive
      protein release.

PMID- 9516432
TI  - The role of DnaJ-like proteins in glucocorticoid receptor.hsp90 heterocomplex
      assembly by the reconstituted hsp90.p60.hsp70 foldosome complex.
AB  - The glucocorticoid receptor (GR) is recovered from hormone-free cells in a
      heterocomplex with the molecular chaperone hsp90, which is required to produce
      the proper folding state for steroid binding. GR.hsp90 heterocomplexes are formed
      by a multiprotein system that appears to exist in all eukaryotic cells. Recently,
      we have reconstituted a receptor.hsp90 heterocomplex assembly system with
      purified rabbit hsp90 and hsp70 and bacterially expressed human p23 and p60. We
      have shown that hsp90, p60, and hsp70 form an hsp90.p60. hsp70 complex that
      converts the GR from a non-steroid binding to a steroid binding form (Dittmar, K.
      D., and Pratt, W. B. (1997) J. Biol. Chem. 272, 13047-13054). The resulting
      GR.hsp90 heterocomplex rapidly disassembles unless p23 is present to bind to the
      ATP-dependent conformation of hsp90 and stabilize its association with the
      receptor (Dittmar, K. D., Demady, D. R., Stancato, L. F., Krishna, P., and Pratt,
      W. B. (1997) J. Biol. Chem. 272, 21213-21220). In the current work, we show that
      the purified rabbit hsp70 utilized in prior studies is contaminated with a small
      amount of the rabbit DnaJ homolog hsp40. Elimination of the hsp40 from the
      purified GR.hsp90 assembly system reduces assembly activity, and the activity is
      restored by addition of the purified yeast DnaJ homolog YDJ-1. hsp40 is a
      component of the hsp90.p60.hsp70 foldosome complex isolated from reticulocyte
      lysate with antibody against p60. Under conditions that promote binding of p23 to
      hsp90 (elevated temperature, ATP, Nonidet P-40, molybdate), a five-membered (p23.
      hsp90.p60.hsp70.hsp40) complex of chaperone proteins is formed in reticulocyte
      lysate or from purified proteins. The hsp40-free, purified assembly system has a
      modest level of assembly activity that is maximally potentiated by YDJ-1 when it
      is present at about one-twentieth the concentration of hsp70. Although hsp40 is
      not in the final GR.hsp90 heterocomplex isolated from L cell cytosol, it is in
      the GR.hsp90 heterocomplex assembled in reticulocyte lysate. We conclude that
      hsp40 is a component of the multiprotein hsp90-based chaperone system where it
      potentiates GR.hsp90 heterocomplex assembly.

PMID- 9516433
TI  - Tn5 in vitro transposition.
AB  - This communication reports the development of an efficient in vitro transposition
      system for Tn5. A key component of this system was the use of hyperactive mutant
      transposase. The inactivity of wild type transposase is likely to be related to
      the low frequency of in vivo transposition. The in vitro experiments demonstrate
      the following: the only required macromolecules for most of the steps in Tn5
      transposition are the transposase, the specific 19-bp Tn5 end sequences, and
      target DNA; transposase may not be able to self-dissociate from product DNAs; Tn5
      transposes by a conservative "cut and paste" mechanism; and Tn5 release from the
      donor backbone involves precise cleavage of both 3' and 5' strands at the ends of
      the specific end sequences.

PMID- 9516434
TI  - Molecular characterization of Xenopus embryo heparan sulfate. Differential
      structural requirements for the specific binding to basic fibroblast growth
      factor and follistatin.
AB  - Enzymatic elimination of heparan sulfate (HS) causes abnormal mesodermal and
      neural formation in Xenopus embryos, and HS plays an indispensable role in
      establishing the embryogenesis and tissue morphogenesis during early Xenopus
      development (Furuya, S., Sera, M., Tohno-oka, R., Sugahara, K., Shiokawa, K., and
      Hirabayashi, Y. (1995) Dev. Growth Differ. 37, 337-346). In this study, HS was
      purified from Xenopus embryos to investigate its disaccharide composition and
      binding ability to basic fibroblast growth factor (bFGF) and follistatin (FS),
      the latter being provided in two isoforms with core sequences of 315 and 288
      amino acids (designated FS-315 and FS-288) originating from alternative mRNA
      splicing. Disaccharide composition analysis of the purified Xenopus HS showed the
      preponderance of a disulfated disaccharide unit with uronic acid 2-O-sulfate and
      glucosamine 2-N-sulfate, which has been implicated in the interactions with bFGF.
      Specific binding of the HS to bFGF and FS-288, the COOH-terminal truncated form,
      was observed in the filter binding assay, whereas HS did not bind to FS-315,
      indicating that the acidic Glu-rich domain of FS-315 precluded the binding. The
      binding of the HS to bFGF or FS-288 was markedly inhibited by heparin (HP) and
      various HS preparations, but not by chondroitin sulfate, supporting the binding
      specificity of HS. The binding specificity was further investigated using FS-288
      and bovine intestinal [3H]HS. Competitive inhibition assays of the HS binding to
      FS-288 using size-defined HP oligosaccharides revealed that the minimum size
      required for significant inhibition was a dodecasaccharide, which is larger than
      the pentasaccharide required for bFGF binding. The binding affinity of FS to HS
      increased in the presence of activin, a growth/differentiation factor, which
      could be inactivated by direct binding to FS. These results, taken together,
      indicate that the structural requirement for binding of HS to bFGF and FS is
      different. HS may undergo dynamic changes in its structure during early Xenopus
      embryogenesis in response to the temporal and spatial expression of various
      growth/differentiation factors.

PMID- 9516435
TI  - Disruption of the DT diaphorase (NQO1) gene in mice leads to increased menadione
      toxicity.
AB  - NAD(P)H:quinone oxidoreductase 1 (NQO1) is a flavoenzyme that catalyzes two
      electron reductive metabolism and detoxification of quinones and their
      derivatives leading to protection of cells against redox cycling and oxidative
      stress. To examine the in vivo role of NQO1, a NQO1-null mouse was produced using
      targeted gene disruption. Mice lacking NQO1 gene expression showed no detectable
      phenotype and were indistinguishable from wild-type mice. However, NQO1-null mice
      exhibited increased toxicity when administered menadione compared with wild-type
      mice. These results establish a role for NQO1 in protection against quinone
      toxicity. The NQO1-null mice are a model for NQO1 deficiency in humans and can be
      used to determine the role of this enzyme in sensitivity to toxicity and
      carcinogenesis.

PMID- 9516436
TI  - Inhibition of the hepatitis C virus helicase-associated ATPase activity by the
      combination of ADP, NaF, MgCl2, and poly(rU). Two ADP binding sites on the enzyme
      nucleic acid complex.
AB  - Hepatitis C virus (HCV) helicase has an intrinsic ATPase activity and a nucleic
      acid (poly(rU))-stimulated ATPase activity. The poly(rU)-stimulated ATPase
      activity was inhibited by F- in a time-dependent manner during ATP hydrolysis.
      Inhibition was the result of trapping an enzyme-bound ADP-poly(rU) ternary
      complex generated during the catalytic cycle and was not the result of generating
      enzyme-free ADP that subsequently inhibited the enzyme. However, catalysis was
      not required for efficient inhibition by F-. The stimulated and the intrinsic
      ATPase activities were also inhibited by treatment of the enzyme with F-, ADP,
      and poly(rU). The inhibited enzyme slowly recovered (t1/2 = 23 min) ATPase
      activity after a 2000-fold dilution into assay buffer. The onset of inhibition by
      500 microM ADP and 15 mM F- in the absence of nucleic acid was very slow (t1/2 >
      40 min). However, the sequence of addition of poly(rU) to a diluted solution of
      ADP/NaF-treated enzyme had a profound effect on the extent of inhibition. If the
      ADP/NaF-treated enzyme was diluted into an assay that lacked poly(rU) and the
      assay was subsequently initiated with poly(rU), the treated enzyme was not
      inhibited. Alternatively, if the treated enzyme was diluted into an assay
      containing poly(rU), the enzyme was inhibited. ATP protected the enzyme from
      inhibition by ADP/NaF. The stoichiometry between ADP and enzyme monomer in the
      inhibited enzyme complex was 2, as determined from titration of the ATPase
      activity ([ADP]/[E] = 2.2) and from the number of radiolabeled ADP bound to the
      inhibited enzyme ([ADP]/[E] = 1.7) in the presence of excess NaF, MgCl2, and
      poly(rU). The Hill coefficient for titration of ATPase activity with F- (n = 2.8)
      or MgCl2 (n = 2.1) in the presence of excess ADP and poly(rU) suggested that
      multiple F- and Mg2+ were involved in forming the inhibited enzyme complex. The
      stoichiometry between (dU)18, a defined oligomeric nucleic acid substituting for
      poly(rU), and enzyme monomer in the inhibited enzyme complex was estimated to be
      1 ([(dU)18/[E] = 1.2) from titration of the ATPase activity in the presence of
      excess ADP, MgCl2, and NaF.

PMID- 9516437
TI  - Thermodynamics of fatty acid binding to engineered mutants of the adipocyte and
      intestinal fatty acid-binding proteins.
AB  - We constructed 18 single amino acid mutants of the adipocyte fatty acid-binding
      protein (A-FABP) and 17 of the intestinal fatty acid-binding protein (I-FABP), at
      locations in the fatty acid (FA) binding sites. For each mutant protein, we
      measured thermodynamic parameters that characterize FA binding. Binding
      affinities ranged from about 200-fold smaller to 30-fold larger than the wild
      type (WT) proteins. Thermodynamic parameters revealed that binding affinities
      often inaccurately reported changes in protein-FA interactions because changes in
      the binding entropy and enthalpy were usually compensatory and larger than the
      binding free energy. FA-FABP interactions were quite different for I-FABP and A
      FABP proteins. Binding affinities were larger and decreased to a greater degree
      with increasing FA solubility for most of the I-FABP as compared with the A-FABP
      proteins, consistent with a more hydrophobic binding site for the I-FABP
      proteins. In A-FABP, Ala substitutions for Arg106 and Arg126, which interact with
      the FA carboxylate, reduce affinities by about 100-fold, but in I-FABP, R106A
      increases affinities up to 30-fold. Moreover, in A-FABP, the thermodynamic
      parameters predict that the FA carboxylate location switches from the 126
      position in R106A to the 106 position in R126A. Finally, the A-FABP proteins, in
      contrast to the I-FABP proteins, reveal significant heat capacity changes
      (DeltaCp) upon FA binding, and substitutions at residues Arg106 and Arg126 reduce
      the magnitude of DeltaCp.

PMID- 9516438
TI  - Differential activation of two JNK activators, MKK7 and SEK1, by MKN28-derived
      nonreceptor serine/threonine kinase/mixed lineage kinase 2.
AB  - MKN28-derived nonreceptor type of serine/threonine kinase/mixed lineage kinase 2
      (MST/MLK2) directly phosphorylates and activates SEK1/MKK4/JNKK1/SKK1 in vitro,
      thereby acting as a mitogen-activated protein (MAP) kinase kinase kinase in the
      JNK/SAPK pathway (Hirai, S. -i., Katoh, M., Terada, M., Kyriakis, J. M., Zon, L.
      I., Rana, A., Avruch, J., and Ohno, S. (1997) J. Biol. Chem. 272, 15167-15173).
      The in vitro reconstitution system for the kinase cascade allowed us now to
      identify JNK/SAPK activators involved in the MST/MLK2-dependent activation of
      JNK/SAPK in vivo. We show that at least two distinct MST/MLK2-dependent JNK/SAPK
      activators are present in the fractionated COS-1 cell lysate, and that they
      appear to be SEK1/MKK4/JNKK1/SKK1 and MKK7/JNKK2/SKK4 by Western blot analysis.
      Notably, a majority of the MST/MLK2-dependent JNK/SAPK-activating activity is
      found in MKK7-containing fractions, whereas the MEKK1-dependent activity is
      comparably distributed in SEK1- and MKK7-containing fractions. Moreover, MST/MLK2
      activates recombinant MKK7 more effectively than recombinant SEK1, whereas MEKK1
      activates both to a similar extent. In addition, the deletion analysis on
      MST/MLK2 showed that the kinase domain is responsible for the determination of
      substrate specificity. These results provide a molecular aspect to the
      differential regulation of the two JNK activators by a variety of cellular
      stimuli.

PMID- 9516439
TI  - Specific inhibition of phorbol ester-stimulated phospholipase D by Clostridium
      sordellii lethal toxin and Clostridium difficile toxin B-1470 in HEK-293 cells.
      Restoration by Ral GTPases.
AB  - Activation of m3 muscarinic acetylcholine receptor (mAChR), stably expressed in
      human embryonic kidney (HEK)-293 cells, leads to phospholipase D (PLD)
      stimulation, a process apparently involving Rho GTPases, as shown by studies with
      Clostridium botulinum C3 exoenzyme and Clostridium difficile toxin B (TcdB).
      Direct activation of protein kinase C (PKC) by phorbol esters, such as phorbol 12
      myristate 13-acetate (PMA), also induces PLD stimulation, which is additive to
      the mAChR action and which is only poorly sensitive to inactivation of Rho
      proteins by TcdB. To study whether Ras-like GTPases are involved in PLD
      regulation, we studied the effects of the TcdB variant TcdB-1470 and Clostridium
      sordellii lethal toxin (TcsL), known to inactivate Rac and some members of the
      Ras protein family, on PLD activities. TcdB-1470 and TcsL did not affect basal
      PLD activity and PLD stimulation by mAChR or direct G protein activation. In
      contrast, PMA-induced PLD stimulation was inhibited by TcdB-1470 and TcsL in a
      time- and concentration-dependent manner, without alteration in immunologically
      detectable PKC isozyme levels. In membranes of HEK-293 cells pretreated with TcdB
      1470 or TcsL, basal and stable GTP analog-stimulated PLD activities measured with
      exogenous phosphatidylcholine, in the presence or absence of phosphatidylinositol
      4,5-bisphosphate, were not altered. In contrast, pretreatment with TcdB-1470 and
      TcsL, but not TcdB, strongly reduced PMA-stimulated PLD activity. The addition of
      recombinant Rac1, serving as glucosylation substrate for TcdB, TcsL, and TcdB
      1470, did not restore PLD stimulation by PMA. Furthermore, PMA-stimulated PLD
      activity, suppressed by prior treatment with TcdB-1470 or TcsL, was not rescued
      by the addition of recombinant Ras (RasG12V) or Rap proteins, acting as
      glucosylation substrates for TcsL only (Ras) or TcdB-1470 and TcsL (Rap). In
      contrast, the addition of recombinant Ral proteins (RalA and RalB), glucosylation
      substrates for TscL and TcdB-1470, but not for TcdB, to membranes of TcdB-1470-
      or TcsL-treated cells fully restored PLD stimulation by PMA without altering the
      strict MgATP dependence of PMA-induced PLD stimulation. RalA-mediated restoration
      of PMA-stimulated PLD activity in membranes of TcsL-treated cells was not
      enhanced by coaddition of RasG12V. In conclusion, the data presented indicate
      that TcdB-1470 and TcsL selectively interfere with phorbol ester stimulation of
      PLD and suggest an essential role of Ral proteins in PKC signaling to PLD in HEK
      293 cells.

PMID- 9516440
TI  - The role of the alpha3(VI) chain in collagen VI assembly. Expression of an
      alpha3(VI) chain lacking N-terminal modules N10-N7 restores collagen VI assembly,
      secretion, and matrix deposition in an alpha3(VI)-deficient cell line.
AB  - Collagen VI is a microfibrillar protein found in the extracellular matrix of
      virtually all connective tissues. Three genetically distinct subunits, the
      alpha1(VI), alpha2(VI), and alpha3(VI) chains, associate intracellularly to form
      triple-helical monomers, which then assemble into disulfide-bonded dimers and
      tetramers before secretion. Although sequence considerations suggest that
      collagen VI monomers composed of all three chains are the most stable isoform,
      the precise chain composition of collagen VI remains controversial and
      alternative assemblies containing only alpha1(VI) and alpha2(VI) chains have also
      been proposed. To address this question directly and study the role of the
      alpha3(VI) chain in assembly, we have characterized collagen VI biosynthesis and
      in vitro matrix formation by a human osteosarcoma cell line (SaOS-2) that is
      deficient in alpha3(VI) production. Northern analysis showed an abundance of
      alpha1(VI) and alpha2(VI) mRNAs, but no detectable alpha3(VI) mRNA was apparent
      in SaOS-2 cells. By day 30 of culture, however, small amounts of alpha3(VI) mRNA
      were detected, although the level of expression was still much less than
      alpha1(VI) and alpha2(VI). Collagen VI protein was not detected in SaOS-2 medium
      or cell layer samples until day 30 of culture, demonstrating that despite the
      abundant synthesis of alpha1(VI) and alpha2(VI), no stable collagen VI protein
      was produced without expression of alpha3(VI). The alpha1(VI) and alpha2(VI)
      chains produced in the absence of alpha3(VI) were non-helical and were largely
      retained intracellularly and degraded. The critical role of the alpha3(VI) chain
      in collagen VI assembly was directly demonstrated after stable transfection of
      SaOS-2 cells with an alpha3(VI) cDNA expression construct that lacked 4 of the 10
      N-terminal type A subdomains. The transfected alpha3(VI) N6-C5 chains associated
      with endogenous alpha1(VI) and alpha2(VI) and formed collagen VI dimers and
      tetramers, which were secreted and deposited into an extensive network in the
      extracellular matrix. These data demonstrated that alpha3(VI) is essential for
      the formation of stable collagen VI molecules and subdomains N10-N7 are not
      required for molecular assembly.

PMID- 9516441
TI  - Inducible expression of IkappaBalpha repressor mutants interferes with NF-kappaB
      activity and HIV-1 replication in Jurkat T cells.
AB  - Human immunodeficiency virus (HIV-1) utilizes the NF-kappaB/Rel proteins to
      regulate transcription through NF-kappaB binding sites in the HIV-1 long terminal
      repeat (LTR). Normally, NF-kappaB is retained in the cytoplasm by inhibitory
      IkappaB proteins; after stimulation by multiple activators including viruses,
      IkappaBalpha is phosphorylated and degraded, resulting in NF-kappaB release. In
      the present study, we examined the effect of tetracycline-inducible expression of
      transdominant repressors of IkappaBalpha (TD-IkappaBalpha) on HIV-1
      multiplication using stably selected Jurkat T cells. TD-IkappaBalpha was
      inducibly expressed as early as 3 h after doxycycline addition and dramatically
      reduced both NF-kappaB DNA binding activity and LTR-directed gene activity.
      Interestingly, induced TD-IkappaBalpha expression also decreased endogenous
      IkappaBalpha expression to undetectable levels by 24 h after induction,
      demonstrating that TD-IkappaBalpha repressed endogenous NF-kappaB-dependent gene
      transcription. TD-IkappaBalpha expression also sensitized Jurkat cells to tumor
      necrosis factor-induced apoptosis. De novo HIV-1 infection of Jurkat cells was
      dramatically altered by TD-IkappaBalpha induction, resulting in inhibition of HIV
      1 multiplication, as measured by p24 antigen, reverse transcriptase, and viral
      RNA. Given the multiple functions of the NF-kappaB/IkappaB pathway, TD
      IkappaBalpha expression may interfere with HIV-1 multiplication at several
      levels: LTR-mediated transcription, Rev-mediated export of viral RNA, inhibition
      of HIV-1-induced pro-inflammatory cytokines, and increased sensitivity of HIV-1
      infected cells to apoptosis.

PMID- 9516442
TI  - A novel rhodopsin kinase in octopus photoreceptor possesses a pleckstrin homology
      domain and is activated by G protein betagamma-subunits.
AB  - G protein-coupled receptor kinases (GRKs) play an important role in stimulus
      dependent receptor phosphorylation and desensitization of the receptors.
      Mammalian rhodopsin kinase (RK) and beta-adrenergic receptor kinase (betaARK) are
      the most studied members among known GRKs. In this work, we purified RK from
      octopus photoreceptors for the first time from invertebrate tissues. The
      molecular mass of the purified enzyme was 80 kDa as estimated by SDS
      polyacrylamide gel electrophoresis, and this was 17 kDa larger than that of the
      vertebrate enzymes. Unlike vertebrate RK, octopus RK (ORK) was directly activated
      by betagamma-subunits of a photoreceptor G protein. We examined the effects of
      various known activators and inhibitors of GRKs on the activity of the purified
      ORK and found that their effects were different from those on either bovine RK or
      betaARK. To analyze the primary structure of the enzyme, we cloned the cDNA
      encoding ORK from an octopus retinal cDNA library. The deduced amino acid
      sequence of the cDNA was highly homologous to betaARK over the entire molecule,
      including a pleckstrin homology domain located in the C-terminal region, and
      homology to RK was significantly lower. Furthermore, Western blot analysis of
      various octopus tissues with an antibody against the purified ORK showed that ORK
      is expressed solely in the retina, which confirmed the identity of the enzyme as
      rhodopsin kinase. Thus, ORK appears to represent a unique subgroup in the GRK
      family, which is distinguished from vertebrate RK.

PMID- 9516443
TI  - Evidence for at least two native forms of rabbit muscle adenylate kinase in
      equilibrium in aqueous solution.
AB  - The time course of 8-anilino-1-naphthalenesulfonic acid (ANS) binding to
      adenylate kinase (AK) is a biphasic process. The burst phase ends in the dead
      time of the stopped-flow apparatus (about 15 ms), whereas the slow phase
      completes in about 10 min. A Job's plot tests of the binding stoichiometry
      demonstrates that there is one ANS binding site on AK, but only about 70% of the
      enzyme can rapidly bind with ANS, indicating that the conformation of native AK
      molecules is not homogeneous. Further kinetic analysis shows that the effects of
      ANS and substrates concentration on the burst and slow phase fluorescence
      building agree well with the multiple native forms mechanism. One form (denoted
      N1) binds with ANS, whereas the other (denoted N2) does not. ANS binding to N1
      results in a burst phase fluorescence increase, followed by the interconversion
      of N2 to N1, to give the slow phase ANS binding. Under urea denaturation
      conditions, N2 is easily perturbed by urea and unfolds completely at low
      denaturant concentrations, whereas N1 is relatively resistant to denaturation and
      unfolds at higher denaturant concentrations. The existence of multiple native
      forms in solution may shed some light on the interpretation of the enzyme
      catalytic mechanism.

PMID- 9516444
TI  - Autoactivation of avian urokinase-type plasminogen activator (uPA). A novel mode
      of initiation of the uPA/plasmin cascade.
AB  - In contrast to mammalian urokinase-type plasminogen activator (uPA), which is
      produced and maintained in zymogen form, avian uPA is found in the active two
      chain form in cultures of normal and transformed chicken cells in the absence of
      plasmin, the putative natural activator of pro-uPA. Recombinant chicken uPA (ch
      uPAwt) synthesized in two distinct expression systems also presents in the active
      two-chain form. In addition, conversion to the active uPA in both natural and
      recombinant expression systems could be prevented by uPA-specific inhibitors
      including a monoclonal antibody that uniquely inhibits the catalytic activity of
      ch-uPA. Most significantly, an active site mutant of avian uPA (ch-uPAS353A) that
      lacks catalytic activity is produced and maintained in single-chain form.
      Furthermore, the single-chain ch-uPAS353A mutant can be converted to the two
      chain form by purified active ch-uPAwt. These results strongly indicate an
      autocatalytic mechanism of activation of ch-uPA. Autoactivation appears to be an
      intrinsic property of ch-uPA and may be the initiating molecular event in uPA
      mediated proteolytic cascades.

PMID- 9516445
TI  - The molybdenum cofactor of Escherichia coli nitrate reductase A (NarGHI). Effect
      of a mobAB mutation and interactions with [Fe-S] clusters.
AB  - We have studied the effect of a mobAB mutation and tungstate on molybdo
      molybdopterin-guanine dinucleotide (Mo-MGD) insertion into Escherichia coli
      nitrate reductase (NarGHI). Preparation of fluorescent oxidized derivatives of
      MGD (Form A and Form B) indicates that in a mobAB mutant there is essentially no
      detectable cofactor present in either the membrane-bound (NarGHI) or purified
      soluble (NarGH) forms of the enzyme. Electron paramagnetic resonance
      characterization of membrane-bound cofactor-deficient NarGHI suggests that it has
      altered electrochemistry with respect to the dithionite reducibility of the [Fe
      S] clusters of NarH. Potentiometric titrations of membrane-bound NarGHI indicate
      that the NarH [Fe-S] clusters have midpoint potentials at pH 8.0 (Em,8.0 values)
      of +180 mV ([3Fe-4S] cluster), +130, -55, and -420 mV ([4Fe-4S] clusters) in a
      wild-type background and +180, +80, -35, and -420 mV in a mobAB mutant
      background. These data support the following conclusions: (i) a model for Mo-MGD
      biosynthesis and assembly into NarGHI in which both metal chelation and
      nucleotide addition to molybdopterin precede cofactor insertion; and (ii) the
      absence of Mo-MGD significantly affects Em,8.0 of the highest potential [4Fe-4S]
      cluster.

PMID- 9516446
TI  - Comparative effects of GTPgammaS and insulin on the activation of Rho,
      phosphatidylinositol 3-kinase, and protein kinase N in rat adipocytes.
      Relationship to glucose transport.
AB  - Electroporation of rat adipocytes with guanosine 5'-3-O-(thio)triphosphate
      (GTPgammaS) elicited sizable insulin-like increases in glucose transport and
      GLUT4 translocation. Like insulin, GTPgammaS activated membrane
      phosphatidylinositol (PI) 3-kinase in rat adipocytes, but, unlike insulin, this
      activation was blocked by Clostridium botulinum C3 transferase, suggesting a
      requirement for the small G-protein, RhoA. Also suggesting that Rho may operate
      upstream of PI 3-kinase during GTPgammaS action, the stable overexpression of Rho
      in 3T3/L1 adipocytes provoked increases in membrane PI 3-kinase activity. As with
      insulin treatment, GTPgammaS stimulation of glucose transport in rat adipocytes
      was blocked by C3 transferase, wortmannin, LY294002, and RO 31-8220; accordingly,
      the activation of glucose transport by GTPgammaS, as well as insulin, appeared to
      require Rho, PI 3-kinase, and another downstream kinase, e.g. protein kinase C
      zeta (PKC-zeta) and/or protein kinase N (PKN). Whereas insulin activated both PKN
      and PKC-zeta, GTPgammaS activated PKN but not PKC-zeta. In transfection studies
      in 3T3/L1 cells, stable expression of wild-type Rho and PKN activated glucose
      transport, and dominant-negative forms of Rho and PKN inhibited insulin
      stimulated glucose transport. In transfection studies in rat adipocytes,
      transient expression of wild-type and constitutive Rho and wild-type PKN provoked
      increases in the translocation of hemagglutinin (HA)-tagged GLUT4 to the plasma
      membrane; in contrast, transient expression of dominant-negative forms of Rho and
      PKN inhibited the effects of both insulin and GTPgammaS on HA-GLUT4
      translocation. Our findings suggest that (a) GTPgammaS and insulin activate Rho,
      PI 3-kinase, and PKN, albeit by different mechanisms; (b) each of these signaling
      substances appears to be required for, and may contribute to, increases in
      glucose transport; and (c) PKC-zeta may contribute to increases in glucose
      transport during insulin, but not GTPgammaS, action.

PMID- 9516447
TI  - Mechanism of heparin activation of antithrombin. Role of individual residues of
      the pentasaccharide activating sequence in the recognition of native and
      activated states of antithrombin.
AB  - To determine the role of individual saccharide residues of a specific heparin
      pentasaccharide, denoted DEFGH, in the allosteric activation of the serpin,
      antithrombin, we studied the effect of deleting pentasaccharide residues on this
      activation. Binding, spectroscopic, and kinetic analyses demonstrated that
      deletion of reducing-end residues G and H or nonreducing-end residue D produced
      variable losses in pentasaccharide binding energy of approximately 15-75% but did
      not affect the oligosaccharide's ability to conformationally activate the serpin
      or to enhance the rate at which the serpin inhibited factor Xa. Rapid kinetic
      studies revealed that elimination of the reducing-end disaccharide marginally
      affected binding to the native low-heparin-affinity conformational state of
      antithrombin but greatly affected the conversion of the serpin to the activated
      high-heparin- affinity state, although the activated conformation was still
      favored. In contrast, removal of the nonreducing- end residue D drastically
      affected the initial low-heparin-affinity interaction so as to favor an
      alternative activation pathway wherein the oligosaccharide shifted a preexisiting
      equilibrium between native and activated serpin conformations in favor of the
      activated state. These results demonstrate that the nonreducing-end residues of
      the pentasaccharide function both to recognize the native low-heparin-affinity
      conformation of antithrombin and to induce and stabilize the activated high
      heparin-affinity conformation. Residues at the reducing-end, however, poorly
      recognize the native conformation and instead function primarily to bind and
      stabilize the activated antithrombin conformation. Together, these findings
      establish an important role of the heparin pentasaccharide sequence in
      preferential binding and stabilization of the activated conformational state of
      the serpin.

PMID- 9516448
TI  - Hetero-oligomerization-dependent binding of pig oocyte zona pellucida
      glycoproteins ZPB and ZPC to boar sperm membrane vesicles.
AB  - The zona pellucida surrounding the pig oocyte contains two Mr 55,000
      glycoproteins, pZPB and pZPC, which are orthologues of mouse zona proteins ZP1
      and ZP3, respectively. We previously reported that isolated boar sperm membrane
      vesicles possess high affinity binding sites for partially purified pZPB, but not
      pZPC. Interestingly, co-incubation experiments also implicated pZPB-pZPC
      complexes as potential ligands. We now report that when depleted of a minor pZPC
      contaminant by size exclusion chromatography, pZPB lacks independent binding
      activity. In solid phase binding assays employing immobilized boar sperm
      membranes, pZPB failed to compete with biotin-(pZPB+pZPC) probe, and biotin
      labeled pZPB yielded negligible binding. However, when co-incubated with pZPC
      prior to the binding assays, pZPB acted as a potent competitor, and biotin
      labeled pZPB exhibited high affinity, saturable binding. Binding activity was
      attributed to pZPB-pZPC heterocomplexes, which were detected in co-incubation
      mixtures by size exclusion chromatography and Western blot analysis. In the pig,
      therefore, sperm membranes possess a zona-binding protein with high affinity
      sites for pZPB-pZPC heterocomplexes, but not free glycoprotein subunits.
      Consequently, associative interactions between zona molecules can contribute
      toward both the assembly of the zona matrix and generation of ligands important
      for sperm-zona interactions.

PMID- 9516449
TI  - Up-regulation of transforming growth factor (TGF)-beta receptors by TGF-beta1 in
      COLO-357 cells.
AB  - In the present study we investigated the actions of transforming growth factor
      (TGF)-beta1 on gene induction and cyclin-dependent kinase inhibitors in relation
      to TGF-beta receptor modulation in COLO-357 pancreatic cancer cells. TGF-beta1
      inhibited the growth of COLO-357 cells in a time- and dose-dependent manner and
      caused a rapid but transient increase in plasminogen activator inhibitor-I and
      insulin-like growth factor binding protein-3 mRNA levels. TGF-beta1 caused a
      delayed but sustained increase in the protein levels of the cyclin-dependent
      kinase inhibitors p15(Ink4B), p21(Cip1), and p27(Kip1) and a sustained increase
      in type I and II TGF-beta receptors (TbetaRI and TbetaRII) mRNA and protein
      levels. The protein synthesis inhibitor cycloheximide (10 microg/ml) completely
      blocked the TGF-beta1-mediated increase in TbetaRI and TbetaRII expression.
      Furthermore, a nuclear runoff transcription assay revealed that the increase in
      receptor mRNA levels was due to newly transcribed RNA. There was a significant
      increase in TbetaRI and TbetaRII mRNA levels in confluent cells in comparison to
      subconfluent (</=80% confluent) controls, as well as in serum- starved cells when
      compared with cells incubated in medium containing 10% fetal bovine serum. COLO
      357 cells expressed a normal SMAD4 gene as determined by Northern blot analysis
      and sequencing. These results indicate that TGF-beta1 modulates a variety of
      functions in COLO-357 cells and up-regulates TGF-beta receptor expression via a
      transcriptional mechanism, which has the potential to maximize TGF-beta1
      dependent antiproliferative responses.

PMID- 9516450
TI  - Cloning and functional expression of a cDNA encoding a mammalian sodium-dependent
      vitamin transporter mediating the uptake of pantothenate, biotin, and lipoate.
AB  - Previous studies have shown that a Na+-dependent transport system is responsible
      for the transplacental transfer of the vitamins pantothenate and biotin and the
      essential metabolite lipoate. We now report the isolation of a rat placental cDNA
      encoding a transport protein responsible for this function. The cloned cDNA, when
      expressed in HeLa cells, induces Na+-dependent pantothenate and biotin transport
      activities. The transporter is specific for pantothenate, biotin, and lipoate.
      The Michaelis-Menten constant (Kt) for the transport of pantothenate and biotin
      in cDNA-transfected cells is 4.9 +/- 1.1 and 15.1 +/- 1.2 microM, respectively.
      The transport of both vitamins in cDNA-transfected cells is inhibited by lipoate
      with an inhibition constant (Ki) of approximately 5 microM. The nucleotide
      sequence of the cDNA (sodium-dependent multivitamin transporter (SMVT)) predicts
      a protein of 68.6 kDa with 634 amino acids and 12 potential transmembrane
      domains. Protein data base search indicates significant sequence similarity
      between SMVT and known members of the Na+-dependent glucose transporter family.
      Northern blot analysis shows that SMVT transcripts are present in all of the
      tissues that were tested. The size of the principal transcript is 3.2 kilobases.
      SMVT represents the first Na+-dependent vitamin transporter to be cloned from a
      mammalian tissue.

PMID- 9516451
TI  - Polyethylenimine but not cationic lipids promotes transgene delivery to the
      nucleus in mammalian cells.
AB  - The beta-galactosidase reporter gene, either free or complexed with various
      cationic vectors, was microinjected into mammalian cells. Cationic lipids but not
      polyethylenimine or polylysine prevent transgene expression when complexes are
      injected in the nucleus. Polyethylenimine and to a lesser extent polylysine, but
      not cationic lipids, enhance transgene expression when complexes are injected
      into the cytoplasm. This latter effect was independent of the polymer vector/cDNA
      ionic charge ratio, suggesting that nucleic acid compaction rather than surface
      charge was critical for efficient nuclear trafficking. Cell division was not
      required for nuclear entry. Finally, comparative transfection and microinjection
      experiments with various cell lines confirm that barriers to gene transfer vary
      with cell type. We conclude that polymers but not cationic lipids promote gene
      delivery from the cytoplasm to the nucleus and that transgene expression in the
      nucleus is prevented by complexation with cationic lipids but not with cationic
      polymers.

PMID- 9516453
TI  - Targeted disruption of heat shock transcription factor 1 abolishes
      thermotolerance and protection against heat-inducible apoptosis.
AB  - Heat shock transcription factor 1 (HSF1) is a member of the vertebrate HSF family
      that regulates stress-inducible synthesis of heat shock proteins (HSPs). Although
      the synthesis of the constitutively expressed and inducible members of the heat
      shock family of stress proteins correlates with increased cellular protection,
      their relative contributions in acquired cellular resistance or "thermotolerance"
      in mammalian cells is presently unknown. We report here that constitutive
      expression of multiple HSPs in cultured embryonic cells was unaffected by
      disruption of the murine HSF1 gene. In contrast, thermotolerance was not
      attainable in hsf1(-/-) cells, and this response was required for protection
      against heat-induced apoptosis. We conclude that 1) constitutive and inducibly
      expressed HSPs exhibit distinct physiological functions for cellular maintenance
      and adaptation, respectively, and 2) other mammalian HSFs or distinct
      evolutionarily conserved stress response pathways do not compensate for HSF1 in
      the physiological response to heat shock.

PMID- 9516452
TI  - The roles of individual gamma-carboxyglutamate residues in the solution structure
      and cation-dependent properties of conantokin-T.
AB  - The solution structure of the Ca2+-loaded conantokin-T (con-T), a gamma
      carboxyglutamate (Gla)-containing 21-residue peptide (NH2
      G1EgammagammaY5QKMLgamma10NLRgammaA15EVKKN20A-CONH2,gam ma = Gla), has been
      elucidated by use of distance geometry calculations with experimental distances
      derived from two-dimensional 1H NMR spectroscopy. An end-to-end alpha-helix was
      the dominant conformation in solution, similar to that of apo-con-T, except that
      reorientation of several side chains occurred in the Ca2+-coordinated complex.
      The most notable examples of this were those of Gla10 and Gla14, which were more
      optimally positioned for complexation with Ca2+. In addition to the stabilization
      offered to the alpha-helix by Ca2+ binding, hydrophobic clustering of the side
      chains of Tyr5, Met8, Leu9, and Leu12, and ionic interactions between Lys7 and
      Gla3/Gla10 and between Arg13 and Gla14, along with hydrogen bonding between Gln6
      and Gla10, were among the side chain interactions likely playing a significant
      role in maintenance of the alpha-helical conformation. Docking of Ca2+ in the con
      T structure was accomplished using genetic algorithm-molecular dynamics
      simulation approaches. The results showed that one Ca2+ ion is most likely
      coordinated by four side chain oxygen atoms, two each from Gla10 and Gla14.
      Another bound Ca2+ ion has as its donor sites three oxygen atoms, two from Gla3
      and one from Gln6. To examine the functional roles of the individual Gla
      residues, a series of variant peptides have been synthesized with Ala substituted
      for each Gla residue, and several properties of the resulting variants have been
      examined. The data obtained demonstrated the importance of Gla10 and Gla14 in
      stabilizing binding of the highest affinity Ca2+ site and in governing the
      conformational change induced by Ca2+. The critical nature of Gla3 and Gla4 in
      inhibition of the spermine-induced potentiation of the binding of MK-801 to open
      ion channels of the N-methyl-D-aspartate receptor was established, as well as the
      role of Gla4 in stabilizing the apo-con-T alpha-helical conformation.

PMID- 9516454
TI  - Insertions into the beta3-beta4 hairpin loop of HIV-1 reverse transcriptase
      reveal a role for fingers subdomain in processive polymerization.
AB  - Human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) displays a
      characteristic poor processivity during DNA polymerization. Structural elements
      of RT that determine processivity are poorly understood. The three-dimensional
      structure of HIV-1 RT, which assumes a hand-like structure, shows that the
      fingers, palm, and thumb subdomains form the template-binding cleft and may be
      involved in determining the degree of processivity. To assess the influence of
      fingers subdomain of HIV-1 RT in polymerase processivity, two insertions were
      engineered in the beta3-beta4 hairpin of HIV-1NL4-3 RT. The recombinant mutant
      RTs, named FE20 and FE103, displayed wild type or near wild type levels of RNA
      dependent DNA polymerase activity on all templates tested and wild type or near
      wild type-like sensitivities to dideoxy-NTPs. When polymerase activities were
      measured under conditions that allow a single cycle of DNA polymerization, both
      of the mutants displayed 25-30% greater processivity than wild type enzyme.
      Homology modeling the three-dimensional structures of wild type HIV-1NL4-3 RT and
      its finger insertion mutants revealed that the extended loop between the beta3
      and beta4 strands protrudes into the cleft, reducing the distance between the
      fingers and thumb subdomains to approximately 12 A. Analysis of the models for
      the mutants suggests an extensive interaction between the protein and template
      primer, which may reduce the degree of superstructure in the template-primer. Our
      data suggest that the beta3-beta4 hairpin of fingers subdomain is an important
      determinant of processive polymerization by HIV-1 RT.

PMID- 9516455
TI  - Differential muscle-type expression of the Drosophila troponin T gene. A 3-base
      pair microexon is involved in visceral and adult hypodermic muscle specification.
AB  - The complete genomic organization of the Drosophila troponin T (TnT) gene shows
      many interesting features, including the presence of a microexon of only 3
      nucleotides conserved among Drosophilidae. It is the smallest bona fide exon so
      far described, placing a new lower limit on the nucleotide number required for
      correct splicing. Four muscle-type specific transcripts are generated by
      developmentally regulated alternative splicing. Exons 3, 4, and 5 are absent in
      the transcript present in jump and flight muscles. A total of 11 exons are
      present in the adult hypodermic muscles transcript, whereas the microexon is
      absent in the larval hypodermic musculature. The two isoforms differ in a lysine
      residue. Post-translational regulation of the flight muscles/tergal depressor of
      the trochanter-specific isoform is involved in flight and/or jump function. The
      interaction domains of TnT in the tropomyosin-troponin complex are strongly
      conserved in the known vertebrate and invertebrate TnT sequences, whereas the
      terminal regions show an important variability. The COOH-terminal region shows
      important phylogenetic variations, whereas the NH2-terminal domain is associated
      with specific muscle types in a particular organism, a finding that discloses a
      selective value for these domains in the functionality of distinct muscles in
      different organisms.

PMID- 9516456
TI  - cAMP stimulates osteoblast-like differentiation of calcifying vascular cells.
      Potential signaling pathway for vascular calcification.
AB  - The role of the cAMP signaling pathway in vascular calcification was investigated
      using calcifying vascular cells (CVC) derived from primary aortic medial cell
      cultures. We previously showed that CVC have fibroblastic morphology and express
      several osteoblastic differentiation markers. After confluency, they aggregate
      into cellular condensations, which later mature into nodules where mineralization
      is localized. Here, we investigated the effects of cAMP on CVC differentiation
      because it plays a role in both osteoblastic differentiation and vascular
      disease. Dibutyryl-cAMP or forskolin treatment of CVC for 3 days induced
      osteoblast-like "cuboidal" morphology, inhibited proliferation, and enhanced
      alkaline phosphatase activity, all early markers of osteoblastic differentiation.
      Isobutylmethylxanthine and cholera toxin had the same effects. Treatment of CVC
      with pertussis toxin, however, did not induce the morphological change or
      increase alkaline phosphatase activity, although it inhibited CVC proliferation
      to a similar extent. cAMP also increased type I procollagen production and gene
      expression of matrix gamma-carboxyglutamic acid protein, recently shown to play a
      role in in vivo vascular calcification. cAMP inhibited the expression of
      osteopontin but did not affect the expression of osteocalcin and core binding
      factor. Prolonged cAMP treatment enhanced matrix calcium-mineral incorporation
      but inhibited the condensations resulting in diffuse mineralization throughout
      the monolayer of cells. Treatment of CVC with a protein kinase A-specific
      inhibitor, KT5720, inhibited alkaline phosphatase activity and mineralization
      during spontaneous CVC differentiation. These results suggest that the cAMP
      pathway promotes in vitro vascular calcification by enhancing osteoblast-like
      differentiation of CVC.

PMID- 9516457
TI  - Binding of basic fibroblast growth factor to fibrinogen and fibrin.
AB  - Fibrin is formed at sites of tissue injury and provides the temporary matrix
      needed to support the initial endothelial cell responses needed for vessel
      repair. Basic fibroblast growth factor (bFGF) also acts at sites of injury and
      stimulates similar vascular cell responses. We have, therefore, investigated
      whether there are specific interactions between bFGF and fibrinogen and fibrin
      that could play a role in coordinating these actions. Binding studies were
      performed using bFGF immobilized on Sepharose beads and soluble 125I-labeled
      fibrinogen and also using Sepharose-immobilized fibrinogen and soluble 125I-bFGF.
      Both systems demonstrated specific and saturable binding. Scatchard analysis
      indicated two classes of binding sites for each with Kd values of 1.3 and 260 nM
      using immobilized bFGF; and Kd values of 0.9 and 70 nM using immobilized
      fibrinogen. After conversion of Sepharose-immobilized fibrinogen to fibrin by
      treatment with thrombin, bFGF also demonstrated specific and saturable binding
      with two classes of binding sites having Kd values of 0.13 and 83 nM. Fibrin
      binding was also investigated by clotting a solution of bFGF and fibrinogen, and
      two classes of binding sites were demonstrated using this system with Kd values
      of 0.8 and 261 nM. The maximum molar binding ratios of bFGF to fibrinogen were
      between 2.0 and 4.0 with the four binding systems. We conclude that bFGF binds
      specifically and saturably to fibrinogen and fibrin with high affinity, and this
      may have implications regarding the localization of its effect at sites of tissue
      injury.

PMID- 9516458
TI  - CD95 (Fas/APO-1) induces ceramide formation and apoptosis in the absence of a
      functional acid sphingomyelinase.
AB  - CD95 is a potent inducer of apoptosis. It activates the caspase cascade, but also
      induces ceramide (Cer) production, reportedly involving acid sphingomyelinase
      (aSMase) activity. A role for Cer as a second messenger for apoptosis induction
      was proposed, based on the finding that synthetic Cer analogues can induce cell
      death. We have tested whether aSMase is required for 1) apoptosis induction and
      2) Cer production by CD95. For this purpose, we have used cultured Niemann-Pick
      disease (NPD) lymphoid cells with a defined mutation (R600H) in the aSMase
      protein. Despite their inherited deficiency of aSMase, we found that these cells
      readily undergo apoptosis upon CD95 stimulation. After retrovirus-mediated gene
      transfer of the aSMase cDNA, the transduced (i.e. "corrected") NPD cells showed
      neither increased levels of apoptosis nor altered kinetics of caspase-8 and
      caspase-3 activation and apoptosis induction as compared with empty vector
      transduced cells. The slow sustained elevation of Cer levels in response to CD95,
      which we have previously documented for Jurkat T cells (Tepper, A. D., Boesen-de
      Cock, J. G. R., de Vries, E., Borst, J., and van Blitterswijk, W. J. (1997) J.
      Biol. Chem. 272, 24308-24312), was similarly found in NPD cells. Moreover, the
      kinetics of Cer formation remained unaffected after aSMase transduction. These
      results indicate that this Cer does not result from aSMase activity. We conclude
      that aSMase is not required for and does not facilitate CD95-mediated apoptosis
      and that it is not responsible for the late Cer response.

PMID- 9516459
TI  - Tumor necrosis factor-alpha induces interleukin-6 production and integrin ligand
      expression by distinct transduction pathways.
AB  - Tumor necrosis factor-alpha (TNF-alpha) is a pleiotropic cytokine that elicits a
      large number of biological effects. However, the intracellular signaling
      mechanisms that are responsible for the TNF-alpha effects remain largely unknown.
      We have previously demonstrated that cultured mouse Sertoli cells, after TNF
      alpha treatment, increase the surface expression of adhesion molecules such as
      intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1
      (VCAM-1) and interleukin-6 (IL-6) production (Riccioli, A., Filippini, A., De
      Cesaris, P., Barbacci, E., Stefanini, M., Starace, G., and Ziparo, E. (1995)
      Proc. Natl. Acad. Sci. U.S.A. 92, 5808-5812). Here, we show that, in cultured
      Sertoli cells, TNF-alpha activates the mitogen-activated protein kinase pathway
      (p38, c-Jun N-terminal protein kinase/stress-activated protein kinase, and the
      p42/p44 mitogen-activated protein kinases) as revealed by an increased
      phosphorylation of p38, activating transcription factor-2, c-Jun, and Elk-1.
      Furthermore, our data indicate that the biological effects induced by TNF-alpha
      in Sertoli cells (enhancement of ICAM-1, VCAM-1, and IL-6 expression) depend on
      the activation of different signaling pathways. SB203580, a highly specific p38
      inhibitor, does not affect ICAM-1 and VCAM-1 expression, but strongly inhibits IL
      6 production. Moreover, interferon-gamma, which up-regulates adhesion molecule
      expression and reduces IL-6 production, does not induce phosphorylation of p38.
      Our data strongly support the hypothesis that, in response to TNF-alpha,
      activation of p38 leads to IL-6 production, whereas ICAM-1 and VCAM-1 expression
      could be induced by activation of the c-Jun N-terminal protein kinase/stress
      activated protein kinase pathway.

PMID- 9516460
TI  - Characterization of the hematopoietic transcription factor NF-E2 in primary
      murine megakaryocytes.
AB  - Biochemical analysis of megakaryocytes, the precursors of blood platelets, is
      limited by their rarity in vivo, and studies on lineage-specific gene expression
      have been conducted exclusively in cell lines with limited megakaryocytic
      potential. Mice lacking the transcription factor NF-E2 display arrested
      megakaryocyte differentiation and profound thrombocytopenia. To study the
      heterodimeric NF-E2 protein in primary cells, we cultured mouse fetal livers with
      the c-Mpl ligand, obtained highly enriched megakaryocyte populations, and readily
      detected NF-E2 activity in nuclear extracts. As in erythroid cells, p45 NF-E2 is
      the only large subunit in primary megakaryocytes that dimerizes with distinct
      small Maf proteins to constitute a heterogeneous NF-E2 complex. Whereas p18/MafK
      is the predominant small Maf protein in erythroid cells, the related polypeptides
      MafG and/or MafF predominate in megakaryocytes. Although this represents the
      first example of differential small Maf protein expression among closely related
      blood lineages, the DNA-binding specificity of NF-E2 is similar in both cell
      types. Although the megakaryocyte protein preferentially binds an asymmetric AP-1
      related motif, it also recognizes cAMP-responsive element-related sequences,
      albeit with lower affinity, and nucleotides outside the core sequence influence
      the DNA-protein interaction. These results demonstrate the feasibility of
      biochemical studies on primary murine megakaryocytes and provide a basis to
      dissect the critical functions of NF-E2 in megakaryocyte differentiation.

PMID- 9516461
TI  - Purification and characterization of a new eukaryotic protein translation factor.
      Eukaryotic initiation factor 4H.
AB  - A new protein with translational activity has been identified on the basis of its
      ability to stimulate translation in an in vitro globin synthesis assay deficient
      in eukaryotic initiation factor (eIF) 4B and eIF4F. This protein has been
      purified to greater than 80% homogeneity from rabbit reticulocyte lysate and has
      been given the name eIF4H. eIF4H was shown to stimulate the in vitro activities
      of eIF4B and eIF4F in globin synthesis, as well as the in vitro RNA-dependent
      ATPase activities of eIF4A, eIF4B, and eIF4F. Three tryptic fragments of eIF4H
      yielded amino acid sequences that were 100% identical to a human sequence found
      in the GeneBankTM that codes for a previously uncharacterized protein
      (HUMORFU_1). The calculated molecular weight of the protein encoded by this
      sequence, its predicted cyanogen bromide fragmentation, and calculated
      isoelectric point are all consistent with those determined experimentally for
      eIF4H. Also, the presence of an RNA recognition motif within HUMORFU_1 suggests
      that eIF4H may interact with mRNA. We conclude that this newly characterized
      protein, eIF4H, functions to stimulate the initiation of protein synthesis at the
      level of mRNA utilization, and is encoded by the gene for HUMORFU_1.

PMID- 9516462
TI  - Regulation of iron regulatory protein 1 during hypoxia and hypoxia/reoxygenation.
AB  - Given the important relationship between O2 and iron (Fenton chemistry) a study
      was undertaken to characterize the effects of hypoxia, as well as subsequent
      reoxygenation, on the iron-regulatory proteins 1 and 2 (IRP1 and IRP2) in a rat
      hepatoma cell line. IRP1 and IRP2 are cytosolic RNA-binding proteins that bind
      RNA stem-loops located in the 5'- or 3'-untranslated regions of specific mRNAs
      encoding proteins that are involved in iron homeostasis. In cells exposed to
      hypoxia, IRP1 RNA binding was decreased approximately 2. 8-fold after a 6-h
      exposure to 3% O2. Hypoxic inactivation of IRP1 was abolished when cells were
      pretreated with the iron chelator desferrioxamine, indicating a role for iron in
      inactivation. IRP1 inactivation was reversible since re-exposure of hypoxically
      treated cells to 21% O2 increased RNA binding activity approximately 7-fold after
      21 h with an increase in activity seen as early as 1-h post-reoxygenation. IRP1
      protein levels were unaffected during hypoxia as well as during reoxygenation.
      Whereas the protein synthesis inhibitor cycloheximide did not block IRP1
      inactivation during hypoxia, it completely blocked IRP1 reactivation during
      subsequent reoxygenation. Reactivation of IRP1 during reoxygenation was also
      partially blocked by the phosphatase inhibitor okadaic acid. Finally, reactivated
      IRP1 was found to be resistant to inactivation by exogenous iron known to down
      regulate its activity during normoxia. These data demonstrate that IRP1 RNA
      binding activity is post-translationally regulated during hypoxia and
      hypoxia/reoxygenation. Regulation of IRP1 by changing oxygen tension may provide
      a novel mechanism for post-transcriptionally regulating gene expression under
      these stresses.

PMID- 9516463
TI  - Protein kinase C-theta phosphorylation of moesin in the actin-binding sequence.
AB  - Moesin, a member of the ezrin-radixin-moesin (ERM) family of
      membrane/cytoskeletal linkage proteins, is known to be threonine-phosphorylated
      at Thr558 in activated platelets within its conserved putative actin-binding
      domain. The pathway leading to this phosphorylation step and its control have not
      been previously elucidated. We have detected and characterized reactions leading
      to moesin phosphorylation in human leukocyte extracts. In vitro phosphorylation
      of endogenous moesin, which was identified by peptide microsequencing, was
      dependent on phosphatidylglycerol (PG) or to a lesser extent,
      phosphatidylinositol (PI), but not phosphatidylserine (PS) and diacylglycerol
      (DAG). Analysis of charge shifts, phosphoamino acid analysis, and stoichiometry
      was consistent with a single phosphorylation site. By using mass spectroscopy and
      direct microsequencing of CNBr fragments of phospho-moesin, the phosphorylation
      site was identified as KYKT*LRQIR (where * indicates the phosphorylation site)
      (Thr558), which is conserved in the ERM family. Recombinant moesin demonstrated
      similar in vitro phospholipid-dependent phosphorylation compared with the
      endogenous protein. The phosphorylation site sequence of moesin displays a high
      degree of conservation with the pseudosubstrate sequences of the protein kinase C
      (PKC) family. We identified the kinase activity as PKC-theta on the basis of
      immunodepletion of the moesin kinase activity and copurification of PKC-theta
      with the enzymic activity. We further demonstrate that PKC-theta displays a
      preference for PG vesicles over PI or PS/DAG, with minimal activation by DAG, as
      well as specificity for moesin compared with myelin basic protein, histone H1, or
      other cellular proteins. Expression of a human His6-tagged PKC-theta in Jurkat
      cells and purification by Ni2+ chelate chromatography yield an active enzyme that
      phosphorylates moesin. PG vesicle binding experiments with expressed PKC-theta
      and moesin demonstrate that both bind to vesicles independently of one another.
      Thus, PKC-theta is identified as a major kinase within cells with specificity for
      moesin and with activation under non-classical PKC conditions. It appears likely
      that this activity corresponds to a specific intracellular pathway controlling
      the function of moesin as well as other ERM proteins.

PMID- 9516465
TI  - Characterization of the rat Star gene that encodes the predominant 3.5-kilobase
      pair mRNA. ACTH stimulation of adrenal steroids in vivo precedes elevation of
      Star mRNA and protein.
AB  - The steroidogenic acute regulatory protein (STAR) participates in steroidogenesis
      through the mitochondrial transfer of cholesterol to cytochrome P450scc. The rat
      adrenal Star gene is transcribed as a 3. 5-kilobase pair (kb) and 1.6-kb mRNA
      with the larger mRNA predominating ( approximately 85% of total) in vivo.
      Hypophysectomy (HPX) produced a 3-5-fold decrease in Star mRNA along with a loss
      of adrenal steroids, whereas P450scc mRNA decreased by less than 2-fold.
      Adrenocorticotropic hormone (ACTH) treatment of HPX rats maximally stimulated
      steroidogenesis rates within 5 min with over 10-fold elevation of steady state
      blood levels occurring within 10 min. For intact rats there was a 5-10-fold
      larger increase, paralleling previously observed elevations of cholesterol
      cytochrome P450scc association and metabolism in subsequently isolated adrenal
      mitochondria. ACTH did not increase either total STAR protein or a group of
      modified forms until at least 30 min after completion of acute stimulation,
      indicating that elevated translation of STAR protein cannot alone mediate this
      acute stimulation. Parallel slow changes in STAR protein and corticosterone
      formation after ACTH treatment are consistent with participation of STAR forms as
      co-regulators of these hormonal responses. ACTH stimulation of HPX rats increased
      Star mRNA by 2.5-fold within 20 min and by 4.5-fold after 1 h, thus preceding the
      rise in the STAR protein. A 3.5-kb Star cDNA clone isolated from a rat adrenal
      cDNA library exhibited a 0.9-kb open reading frame and a 2.5-kb 3'-untranslated
      region (3'-UTR). The open reading frame sequence differed at only 12 amino acids
      from that of the mouse Star. The rat Star gene seven exons with exon 7 encoding
      the entire 2.5 kb of 3'-UTR of the 3.5-kb mRNA. The 3'-UTR sequence suggests that
      1.6- and 3.5-kb mRNA are formed by an alternative usage of different
      polyadenylation signals. Multiple UUAUUUA(U/A)(U/A) motifs also suggest
      additional regulation through this extended 3'-UTR. Although elevation of STAR
      protein by ACTH does not cause the acute increase in adrenal cholesterol
      metabolism, changes in the turnover or distribution of an active STAR subfraction
      cannot be excluded.

PMID- 9516464
TI  - The intermediate filament protein, vimentin, in the lens is a target for cross
      linking by transglutaminase.
AB  - Mere addition of Ca2+ to a lens cortical homogenate (bovine) generates a series
      of products composed of a variety of high molecular weight vimentin species. The
      Ca2+-induced cross-linking of this cytoskeletal element seems to be mediated by
      the intrinsic transglutaminase of lens, because the reaction could be blocked at
      the monomeric state of vimentin by the inclusion of small synthetic substrates of
      the enzyme dansylcadaverine or dansyl-epsilon-aminocaproyl-Gln-Gln-Ile-Val. These
      compounds are known to compete against the Gln or Lys functionalities of proteins
      that would participate in forming the Nepsilon(gamma-glutamyl)lysine protein-to
      protein cross-links. The cytosolic transglutaminase-catalyzed reactions could be
      reproduced with purified bovine lens vimentin and also with recombinant human
      vimentin preparations. Employing the latter system, we have titrated the
      transglutaminase-reactive sites of vimentin and, by sequencing the dansyl-tracer
      labeled segments of the protein, we have shown that residues Gln453 and Gln460
      served as acceptor functionalities and Lys97, Lys104, Lys294, and Lys439 as
      electron donor functionalities in vimentin. The transglutaminase-dependent
      reaction of this intermediate filament protein might influence the shape and
      plasticity of the fiber cells, and the enzyme-catalyzed cross-linking of
      vimentin, in conjunction with other lens constituents, may contribute to the
      process of cataract formation.

PMID- 9516467
TI  - Regulation of high affinity iron uptake in the yeast Saccharomyces cerevisiae.
      Role of dioxygen and Fe.
AB  - High affinity iron uptake in Saccharomyces cerevisiae requires a metal reductase,
      a multicopper ferroxidase, and an iron permease. Fet3, the apparent ferroxidase,
      is proposed to facilitate iron uptake by catalyzing the oxidation of reductase
      generated Fe(II) to Fe(III) by O2; in this model, Fe(III) is the substrate for
      the iron permease, encoded by FTR1 (Kaplan, J., and O'Halloran, T. V. (1996)
      Science 271, 1510-1512). We show here that dioxygen also plays an essential role
      in the expression of these iron uptake activities. Cells grown anaerobically
      exhibited no Fe(III) reductase or high affinity iron uptake activity, even if
      assayed for these activities under air. Northern blot analysis showed that the
      amount of those mRNAs encoding proteins associated with this uptake was repressed
      in anaerobic cultures but was rapidly induced by exposure of the culture to
      dioxygen. The anaerobic repression was reduced in cells expressing an iron
      independent form of the trans-activator, Aft1, a protein that regulates the
      expression of these proteins. Thus, the effect of oxygenation on this expression
      appeared due at least in part to the state or distribution of iron in the cells.
      In support of this hypothesis, the membrane-permeant Fe(II) chelator, 2, 2'
      bipyridyl, in contrast to the impermeant chelator bathophenanthroline
      disulfonate, caused a strong and rapid induction of these transcripts under
      anaerobic conditions. An increase in the steady-state levels of iron-regulated
      transcripts upon oxygenation or 2,2'-bipyridyl addition occurred within 5 min,
      indicating that a relatively small, labile intracellular pool of Fe(II) regulates
      the expression of these activities. The strength of the anaerobic repression was
      dependent on the low affinity, Fe(II)-specific iron transporter, encoded by FET4,
      suggesting that this Fe(II) pool was linked in part to iron brought into the cell
      via Fet4 protein. The data suggest a model in which dioxygen directly or
      indirectly modulates the Fe(III)/Fe(II) ratio in an iron pool linked to Aft1
      protein while bipyridyl increases this ratio by chelating Fe(II). These results
      indicate that dioxygen both modulates the sensitivity to iron-dependent
      transcriptional regulation and acts as substrate for Fet3 in the ferroxidase
      reaction catalyzed by this ceruloplasmin homologue.

PMID- 9516466
TI  - Transcriptional roles of CCAAT/enhancer binding protein-beta, nuclear factor
      kappaB, and C-promoter binding factor 1 in interleukin (IL)-1beta-induced IL-6
      synthesis by human rheumatoid fibroblast-like synoviocytes.
AB  - The involvement of interleukin (IL)-6 in the pathogenesis of rheumatoid arthritis
      (RA) has been recently demonstrated. IL-1beta stimulated rheumatoid fibroblast
      like synoviocytes (FLSs) to produce IL-6 in a concentration- and time-dependent
      manner. In the present study we investigated how the IL-6 promoter is
      transcriptionally regulated in rheumatoid FLSs in response to a physiologically
      relevant mediator of inflammation, IL-1beta. Deletion analysis showed that the IL
      6 promoter is regulated by two positive elements (located at -159 to -142 base
      pairs (bp) and -77 to -59 bp). Electrophoretic mobility shift assays revealed
      that CCAAT/enhancer binding protein-beta (C/EBPbeta) binding to nucleotides -159
      to -142 bp was constitutively present. The probe corresponding to nucleotides -77
      to -59 bp gave three positive bands. The two slower migrating bands were induced
      by IL-1beta and comprised an nuclear factor (NF)-kappaB p50/p65 heterodimer and a
      p65/p65 homodimer. The faster migrating band was constitutively expressed and
      identified as Epstein-Barr virus C-promoter binding factor 1, CBF1. Site-specific
      mutagenesis analysis demonstrated that the NF-kappaB and CBF1 binding elements
      regulated inducible activity of the IL-6 promoter in response to IL-1beta
      stimulation, whereas the C/EBPbeta binding element mainly regulated basal
      activity. We also provide the first evidence that CBF1 functions as a positive
      regulator of human IL-6 gene transcription.

PMID- 9516468
TI  - Desensitization of beta2-adrenergic receptors with mutations of the proposed G
      protein-coupled receptor kinase phosphorylation sites.
AB  - Tentative identification of the G protein-coupled receptor kinase 2 and 5 (GRK2
      and GRK5) sites of phosphorylation of the beta2-adrenergic receptor (betaAR) was
      recently reported based on in vitro phosphorylation of recombinant receptor
      (Fredericks, Z. L., Pitcher, J. A., and Lefkowitz, R. J. (1996) J. Biol. Chem.
      271, 13796-13803). Phosphorylated residues identified for GRK2 were threonine 384
      and serines 396, 401, and 407. GRK5 phosphorylated these four residues as well as
      threonine 393 and serine 411. To determine if mutation of these sites altered
      desensitization, we have constructed betaARs in which the threonines and serines
      of the putative GRK2 and GRK5 sites were substituted with alanines. These
      constructs were further modified to eliminate the cAMP-dependent protein kinase
      (PKA) consensus sites. Mutants betaARs were transfected into HEK 293 cells, and
      standard kinetic parameters were measured following 10 microM epinephrine
      treatment of cells. The mutant and wild type (WT) receptors were all desensitized
      89-94% after 5 min of 10 microM epinephrine stimulation and 96-98% after a 30-min
      pretreatment. There were no significant changes observed for any of the mutant
      betaARs relative to the WT in the extent of 10 microM epinephrine-induced
      internalization (77-82% after 30 min). Epinephrine treatment for 1 min induced a
      rapid increase in the phosphorylation of the GRK5 and PKA- mutant betaARs as well
      as the WT. We conclude that sites other than the GRK2 and GRK5 sites identified
      by in vitro phosphorylation are involved in mediating the major effects of the in
      vivo GRK-dependent desensitization of the betaAR.

PMID- 9516469
TI  - Cloning of the multipartite promoter of the sodium-calcium exchanger gene NCX1
      and characterization of its activity in vascular smooth muscle cells.
AB  - The sodium-calcium exchange activity is mediated by proteins encoded in a small
      gene family, of which the gene NCX1 is ubiquitously expressed in mammalian
      tissues. In this study, the multipartite promoter of this gene was analyzed in
      the human and rat genomes by means of DNA cloning, reverse transcriptase
      polymerase chain reaction, and transient transfection of fusion constructs with
      the firefly luciferase gene into cultured rat aortic smooth muscle cells. The
      gene-proximal promoter, located 30 kilobase pairs (kb) away from the first coding
      exon 2, has features of a GC-rich housekeeping promoter and is apparently always
      active; in specific tissues, however, it is augmented by one or two additional
      promoters, located either within 1.5 kb upstream of it, or 35 kb upstream. The
      gene proximal promoter shows the highest activity in aortic smooth muscle cells.
      In mammalian species transcripts from all three promoters undergo splicing via an
      intermediate, containing two noncoding exons, of which the downstream one is
      normally not present in the terminal splicing product.

PMID- 9516470
TI  - The nucleolin binding activity of hepatitis delta antigen is associated with
      nucleolus targeting.
AB  - Hepatitis delta antigens (HDAgs) are important for the replication and assembly
      of hepatitis delta virus (HDV). To understand the association between HDAgs and
      cellular proteins and the mechanism of viral multiplication, we have studied the
      interaction between HDAgs and nucleolin, a major nucleolar phosphoprotein. The
      interaction between HDAgs and nucleolin was first demonstrated by
      immunofluorescence staining studies. HDAgs and endogenous nucleolin were
      colocalized in the nucleoli of cultured cells transfected with plasmids encoding
      the small and large HDAg. Coimmunoprecipitation results indicated that the NH2
      terminal domain of HDAg was essential for its binding to nucleolin. In vitro
      ligand binding assays revealed two nucleolin binding sites, NBS1 and NBS2. Each
      spanned amino acid residues 35-50 and 51-65, respectively, with a conserved core
      sequence K(K/R)XK. HDV replication was modulated by exogenous human nucleolin. In
      addition, a small HDAg mutant S-d65/75, which possesses both NBS1 and NBS2, was
      capable of transactivating HDV replication, whereas the small HDAg mutant S
      d50/75, which retained NBS1 but not NBS2, was unable to support the replication
      of HDV. Thus, the nucleolin binding activity of HDAg is critical for its
      nucleolar targeting and is involved in the modulation of HDV replication.

PMID- 9516471
TI  - Construction and binding kinetics of a soluble granulocyte-macrophage colony
      stimulating factor receptor alpha-chain-Fc fusion protein.
AB  - Granulocyte-macrophage colony-stimulating factor (GM-CSF) activity is mediated by
      a cellular receptor (GM-CSFR) that is comprised of an alpha-chain (GM-CSFRalpha),
      which specifically binds GM-CSF, and a beta-chain (betac), shared with the
      interleukin-3 and interleukin-5 receptors. GM-CSFRalpha exists in both a
      transmembrane (tmGM-CSFRalpha) and a soluble form (sGM-CSFRalpha). We designed an
      sGM-CSFRalpha-Fc fusion protein to study GM-CSF interactions with the GM
      CSFRalpha. The construct was prepared by fusing the coding region of the sGM
      CSFRalpha with the CH2-CH3 regions of murine IgG2a. Purified sGM-CSFRalpha-Fc ran
      as a monomer of 60 kDa on reducing SDS-polyacrylamide gel electrophoresis but
      formed a trimer of 160-200 kDa under nonreducing conditions. The sGM-CSFRalpha-Fc
      bound specifically to GM-CSF as demonstrated by standard and competitive
      immunoassays, as well as by radioligand assay with 125I-GM-CSF. The sGM-CSFRalpha
      Fc also inhibited GM-CSF-dependent cell growth and therein is a functional
      antagonist. Kinetics of sGM-CSFRalpha-Fc binding to GM-CSF were evaluated using
      an IAsys biosensor (Affinity Sensors, Paramus, NJ) with two assay systems. In the
      first, the sGM-CSFRalpha-Fc was bound to immobilized staphylococcal protein A on
      the biosensor surface, and binding kinetics of GM-CSF in solution were
      determined. This revealed a rapid koff of 2.43 x 10(-2)/s. A second set of
      experiments was performed with GM-CSF immobilized to the sensor surface and the
      sGM-CSFRalpha-Fc in solution. The dissociation rate constant (koff) for the sGM
      CSFRalpha-Fc trimer from GM-CSF was 1.57 x 10(-3)/s, attributable to the higher
      avidity of binding in this assay. These data indicate rapid dissociation of GM
      CSF from the sGM-CSFRalpha-Fc and suggest that in vivo, sGM-CSFRalpha may need to
      be present in the local environment of a responsive cell to exert its antagonist
      activity.

PMID- 9516472
TI  - A role for Sp and helix-loop-helix transcription factors in the regulation of the
      human Id4 gene promoter activity.
AB  - Id family helix-loop-helix (HLH) proteins are involved in the regulation of
      proliferation and differentiation of several cell types. To identify cis- and
      trans-acting factors that regulate Id4 gene expression, we have analyzed the
      promoter regulatory sequences of the human Id4 gene in transient transfections
      and gel mobility shift assays. We have identified two functional elements, both
      located downstream from the TATA motif, that control Id4 promoter activity. One
      element contains a consensus E-box, and we demonstrated that the protein complex
      binding to the E-box contains the bHLH-zip upstream stimulatory factor (USF)
      transcription factor. Enforced expression of USF1 leads to E-box-mediated
      stimulation of promoter activity. The E-box also mediated stimulatory effects of
      several bHLH transcription factors, and co-expression of Id4 blocked the
      stimulatory effect mediated by the bHLH factors. A second element is a GA motif,
      located downstream from the transcriptional start sites, mutation of which
      resulted in a 20-fold increase in transcriptional activity. Gel-shift analysis
      and transfections into Drosophila Schneider SL2 cells showed that the repressor
      element is recognized by both Sp1 and Sp3 factors. These data suggest that Id4
      transcription control is highly complex, involving both negative and positive
      regulatory elements, including a novel inhibitory function exerted by Sp1 and Sp3
      transcription factors.

PMID- 9516473
TI  - Genomic structure and promoter activity of the mouse polysialic acid synthase
      (mST8Sia IV/PST) gene.
AB  - The mouse gene encoding ST8Sia IV/PST, one of two polysialic acid synthases, was
      isolated and characterized. The mST8Sia IV/PST gene was found to comprise over 60
      kilobases and to be composed of five exons. Primer extension analysis revealed
      that transcription started from 333 nucleotides upstream of the translational
      initiation site. Transfection with nested deletion mutants of the 5'-flanking
      region fused to the luciferase reporter gene revealed that the promoter activity
      of the -107/+145 region was correlated with the gene expression of mST8Sia IV/PST
      in embryonal carcinoma P19 and neuroblastoma F11 cells. This proximal promoter
      region lacks an apparent TATA box but has putative binding sites for
      transcription factors Sp1 and NF-Y (CCAAT binding protein) at nucleotide
      positions -66/-57 and -47/-37, respectively. Individual deletions and mutations
      of the inverted Sp1 binding site or inverted NF-Y binding site caused significant
      reduction of the promoter activity, indicating that each binding site was
      involved in essential transcription control. Mobility shift assaying also
      revealed that Sp1 and NF-Y in a nuclear extract of P19 cells bind to the promoter
      region of the mST8Sia IV/PST gene. Deletion of the region from -60 to -40, which
      contains parts of both the Sp1 and NF-Y binding sites, completely abolished the
      promoter activity, suggesting that both Sp1 and NF-Y are synergetically involved
      in transcription regulation of the mST8Sia IV/PST gene in P19 and F11 cells.
      Although the overall structures of the two polysialic acid synthase genes (ST8Sia
      II/STX and IV/PST) are very similar, there is no extensive sequence homology
      between the 5'-flanking regions of the ST8Sia II/STX and IV/PST genes, suggesting
      that these two genes are expressed under different regulatory systems.

PMID- 9516474
TI  - Involvement of phosphatidate phosphohydrolase in arachidonic acid mobilization in
      human amnionic WISH cells.
AB  - Prostaglandins are known to play a central role in the initiation of labor in
      humans, and amnionic cells constitute a major source of these compounds.
      Prostaglandin synthesis and release by amnion cells in response to hormones and
      ligands takes place after a characteristic 4-5 h lag. However, we report herein
      that free arachidonic acid (AA), the metabolic precursor of prostaglandins, can
      be induced at much shorter times (1 h) in human amnionic WISH cells by phorbol 12
      myristate 13-acetate (PMA) through activation of protein kinase Calpha
      (PKCalpha). WISH cells were found to possess both cytosolic group IV
      phospholipase A2 (cPLA2) and Group VI Ca2+-independent phospholipase A2 (iPLA2).
      Of these, the cPLA2 was found to be the likely mediator of AA mobilization in PMA
      activated WISH cells. PMA also activates phospholipase D (PLD) in these cells and
      ethanol, a compound that inhibits PLD-mediated phosphatidic acid (PA) formation,
      blocked AA release. Moreover, prevention of PA dephosphorylation by the PA
      phosphohydrolase inhibitors propranolol and bromoenol lactone, resulted in
      inhibition of AA release by PMA-treated WISH cells. Collectively, these data
      suggest that activation of cPLA2 and attendant AA release by phorbol esters in
      WISH cells requires prior generation of DAG by phosphatidate phosphohydrolase.

PMID- 9516475
TI  - Gene expression in scrapie. Cloning of a new scrapie-responsive gene and the
      identification of increased levels of seven other mRNA transcripts.
AB  - To define genes associated with or responsible for the neurodegenerative changes
      observed in transmissible spongiform encephalopathies, we analyzed gene
      expression in scrapie-infected mouse brain using "mRNA differential display." The
      RNA transcripts of eight genes were increased 3-8-fold in the brains of scrapie
      infected animals. Five of these genes have not previously been reported to
      exhibit increased expression in this disease: cathepsin S, the C1q B-chain of
      complement, apolipoprotein D, and two previously unidentified genes denominated
      scrapie-responsive gene (ScRG)-1 and ScRG-2, which are preferentially expressed
      in brain tissue. Increased expression of the three remaining genes, beta2
      microglobulin, F4/80, and metallothionein II, has previously been reported to
      occur in experimental scrapie. Kinetic analysis revealed a concomitant increase
      in the levels of ScRG-1, cathepsin S, the C1q B-chain of complement, and beta2
      microglobulin mRNA as well as glial fibrillary acidic protein and F4/80
      transcripts, markers of astrocytosis and microglial activation, respectively. In
      contrast, the level of ScRG-2, apolipoprotein D, and metallothionein II mRNA was
      only increased at the terminal stage of the disease. ScRG-1 mRNA was found to be
      preferentially expressed in glial cells and to code for a short protein of 47
      amino acids with a strong hydrophobic N-terminal region.

PMID- 9516476
TI  - Fusicoccin effect on the in vitro interaction between plant 14-3-3 proteins and
      plasma membrane H+-ATPase.
AB  - A 17-amino acid peptide was selectively cleaved from the highly variant C
      terminus of the 33-kDa 14-3-3 isoform occurring in fusicoccin receptor
      preparations from maize and was sequenced. The determined C-terminal sequence was
      identical to that of the already known maize 14-3-3 homolog GF14-6, thus
      prompting the use of recombinant GF14-6 in an in vitro protein-protein
      interaction study. The cDNA of GF14-6 was expressed in Escherichia coli as a 32P
      phosphorylatable glutathione S-transferase fusion protein and was used as a probe
      in overlay experiments with H+-ATPase partially purified from maize roots. The
      results demonstrated that the recombinant protein specifically bound to H+
      ATPase. The binding was dependent on Mg2+ and was strongly increased by
      fusicoccin. Controlled trypsin digestion of H+-ATPase abolished the association
      with GF14-6, a finding that was suggestive of an interaction with the C terminus
      of the enzyme. To confirm this result, the C-terminal domain of H+-ATPase was
      expressed as a glutathione S-transferase fusion peptide and was used in overlay
      experiments. GF14-6 was also able to bind to the isolated C terminus, but only in
      the presence of fusicoccin.

PMID- 9516477
TI  - Angiotensin II-induced association of phospholipase Cgamma1 with the G-protein
      coupled AT1 receptor.
AB  - An early event in signaling by the G-protein-coupled angiotensin II (Ang II) AT1
      receptor in vascular smooth muscle cells is the tyrosine phosphorylation and
      activation of phospholipase Cgamma1 (PLCgamma1). In the present study, we show
      that stimulation of this event by Ang II in vascular smooth muscle cells is
      accompanied by binding of PLCgamma1 to the AT1 receptor in an Ang II- and
      tyrosine phophorylation-dependent manner. The PLCgamma1-AT1 receptor interaction
      appears to depend on phosphorylation of tyrosine 319 in a YIPP motif in the C
      terminal intracellular domain of the AT1 receptor and binding of the
      phosphorylated receptor by the most C-terminal of two Src homology 2 domains in
      PLCgamma1. PLCgamma1 thus binds to the same site in the receptor previously
      identified for binding by the SHP-2 phosphotyrosine phosphatase.JAK2 tyrosine
      kinase complex. A single site in the C-terminal tail of the AT1 receptor can,
      therefore, be bound in a ligand-dependent manner by two different downstream
      effector proteins. These data demonstrate that G-protein-coupled receptors can
      physically associate with intracellular proteins other than G proteins, creating
      membrane-delimited signal transduction complexes similar to those observed for
      classic growth factor receptors.

PMID- 9516478
TI  - Prolactin receptor regulates Stat5 tyrosine phosphorylation and nuclear
      translocation by two separate pathways.
AB  - The SH2 domain containing signal transducers and activators of transcription
      (Stat proteins) are effector molecules downstream of cytokine receptors.
      Ligand/receptor engagement triggers Stat proteins tyrosine phosphorylation,
      dimerization, and translocation to the nucleus where they regulate gene
      transcription. Stat5, originally identified as a mammary gland growth factor, is
      an essential mediator of prolactin (PRL)-induced milk protein gene activation.
      Prolactin receptor (PRLR) is a member of the cytokine/growth hormone/PRL receptor
      superfamily. The mechanism through which PRLR modulates Stat5 tyrosine
      phosphorylation, nuclear translocation, and DNA binding was analyzed in HC11
      cells, a mammary epithelial cell line, and 293-LA cells, a human kidney cell line
      stably overexpressing Jak2 kinase. We have found that in HC11 cells, Stat5 is
      specifically activated by PRL treatment, demonstrating that Stat5 is a
      physiological substrate downstream of PRLR. Furthermore, using different forms
      natural forms of the PRLR as well as receptor tyrosine to phenylalanine mutant
      forms, we determined that tyrosine phosphorylation of Stat5 is independent of
      PRLR phosphotyrosines. We established, however, that the C-terminal tyrosine of
      the PRLR Nb2 form, Tyr382, plays an essential positive role in PRLR-dependent
      Stat5 nuclear translocation and subsequently DNA binding. All together, our data
      propose a new model for activation of Stat5 through the PRLR, suggesting that
      Stat5 tyrosine phosphorylation and nuclear translocation are two separately
      regulated events.

PMID- 9516479
TI  - Analysis of Grb7 recruitment by heregulin-activated erbB receptors reveals a
      novel target selectivity for erbB3.
AB  - Heregulin-mediated activation of particular erbB receptor combinations was used
      as a model system to investigate the interaction of erbB3 and erbB4 with the
      adaptor protein growth factor receptor-bound (Grb)7. In human breast cancer cell
      lines, co-immunoprecipitation of Grb7 with both receptors was detected upon
      heregulin stimulation. This association was direct and mediated by the Grb7 Src
      homology (SH)2 domain. Co-expression of erbB2 with erbB3 point mutants was used
      to map Grb7 binding sites. This demonstrated that tyrosine 1180 and 1243
      represent the major and minor sites of Grb7 interaction, respectively. Although
      these recognition sequences possess an Asn residue at +2 relative to the
      phosphotyrosine and therefore represent potential Grb2 binding sites,
      phosphopeptide competition and "pull-down" experiments demonstrated that they
      interact preferentially with the Grb7 versus the Grb2 SH2 domain. Substitution
      analysis indicated that an Arg residue at +3 could act as a selectivity
      determinant, but the effect was context-dependent. Consequently, the Grb2 and
      Grb7 SH2 domains possess overlapping, but distinct, specificities. These studies
      therefore identify Grb7 as an in vivo target of erbB3 and erbB4 and provide an
      underlying mechanism for the ability of erbB3 to recruit Grb7 and not Grb2, a
      property unique among erbB receptors.

PMID- 9516480
TI  - The low molecular weight GTPase Rho regulates myofibril formation and
      organization in neonatal rat ventricular myocytes. Involvement of Rho kinase.
AB  - The assembly of contractile proteins into organized sarcomeric units is one of
      the most distinctive features of cardiac myocyte hypertrophy. In a well
      characterized in vitro model system using cultured neonatal rat ventricular
      myocytes, a subset of G protein-coupled receptor agonists has been shown to
      induce actin-myosin filament organization. Pretreatment of myocytes with C3
      exoenzyme ADP-ribosylated Rho and inhibited the characteristic alpha1-adrenergic
      receptor agonist-induced myofibrillar organization, suggesting involvement of the
      Rho GTPase in cardiac myofibrillogenesis. We used adenoviral mediated gene
      transfer to examine the effects of activated Rho and inhibitory mutants of one of
      its effectors, Rho kinase, in myocytes. Rho immunoreactivity was increased in the
      particulate fraction of myocytes infected with a recombinant adenovirus
      expressing constitutively activated Rho. Rho-infected cells demonstrated a
      striking increase in the assembly and organization of sarcomeric units and in the
      expression of the atrial natriuretic factor protein. These Rho-induced responses
      were markedly inhibited by co-infection with adenoviruses expressing putative
      dominant negative forms of Rho kinase. A parallel pathway involving Ras-induced
      myofibrillar organization and atrial natriuretic factor expression was only
      minimally affected. alpha1-Adrenergic receptor agonist-induced myofibrillogenesis
      was inhibited by some but not all of the Rho kinase mutants. Our data demonstrate
      that activated Rho has profound effects on myofibrillar organization in cardiac
      myocytes and suggest that Rho kinase mediates Rho-induced hypertrophic responses.

PMID- 9516481
TI  - A novel class II phosphoinositide 3-kinase predominantly expressed in the liver
      and its enhanced expression during liver regeneration.
AB  - We report herein the cloning and characterization of a novel class II
      phosphoinositide 3-kinase, termed PI3K-IIgamma, from the cDNA library of
      regenerating rat liver. This cDNA encodes a protein of 1505 amino acids with a
      calculated molecular mass of 170,972 Da. The amino acid sequence of PI3K-IIgamma
      is highly similar to those of class II PI 3-kinases, including murine Cpk-m/p170
      and human HsC2-PI3K. It contains a C2 domain at the C terminus but no
      recognizable protein motifs at its N terminus. PI3K-IIgamma displays a restricted
      substrate specificity for PtdIns and PtdIns 4-P, but not for PtdIns 4,5-P2. By
      epitope tag immunocytochemistry, the immunoreactivity for PI3K-IIgamma is
      localized in the juxtanuclear Golgi region at high levels and also in the plasma
      and nuclear membranes at low levels. By Northern blot analysis and in situ
      hybridization histochemistry, PI3K-IIgamma mRNA expression is confined to the
      liver throughout the development with much higher expression in adult liver than
      in fetal liver. In addition, its expression increases during liver regeneration
      after partial hepatectomy with maximal expression after the growth period,
      suggesting that PI3K-IIgamma may function mainly in highly differentiated hepatic
      cells.

PMID- 9516482
TI  - Interactions of the amino acid residue at position 31 of the c-Ha-Ras protein
      with Raf-1 and RalGDS.
AB  - The Ras and Rap1A proteins can bind to the Raf and RalGDS families. Ras and Rap1A
      have Glu and Lys, respectively, at position 31. In the present study, we analyzed
      the effects of mutating the Glu at position 31 of the c-Ha-Ras protein to Asp,
      Ala, Arg, and Lys on the interactions with Raf-1 and RalGDS. The Ras-binding
      domain (RBD) of Raf-1 binds the E31R and E31K Ras mutants less tightly than the
      wild-type, E31A, and E31D Ras proteins; the introduction of the positively
      charged Lys or Arg residue at position 31 specifically impairs the binding of Ras
      with the Raf-1 RBD. On the other hand, the ability of the oncogenic RasG12V
      protein to activate Raf-1 in HEK293 cells was only partially reduced by the E31R
      mutation but was drastically impaired by the E31K mutation. Correspondingly,
      RasG12V(E31K) as well as Rap1A, but not RasG12V(E31R), exhibited abnormally tight
      binding with the cysteine-rich domain of Raf-1. On the other hand, the E31A,
      E31R, and E31K mutations, but not the E31D mutation, enhanced the RalGDS RBD
      binding activity of Ras, indicating that the negative charge at position 31 of
      Ras is particularly unfavorable to the interaction with the RalGDS RBD.
      RasG12V(E31K), RasG12V(E31A), and Rap1A stimulate the RalGDS action more
      efficiently than the wild-type Ras in the liposome reconstitution assay. All of
      these results clearly show that the sharp contrast between the characteristics of
      Ras and Rap1A, with respect to the interactions with Raf-1 and RalGDS, depends on
      their residues at position 31.

PMID- 9516483
TI  - Kinase suppressor of Ras inhibits the activation of extracellular ligand
      regulated (ERK) mitogen-activated protein (MAP) kinase by growth factors,
      activated Ras, and Ras effectors.
AB  - Kinase suppressor of Ras (KSR) is a loss-of-function allele that suppresses the
      rough eye phenotype of activated Ras in Drosophila and the multivulval phenotype
      of activated Ras in Caenorhabditis elegans. Genetic and biochemical studies
      suggest that KSR is a positive regulator of Ras signaling that functions between
      Ras and Raf or in a pathway parallel to Raf. We examined the effect of mammalian
      KSR expression on the activation of extracellular ligand-regulated (ERK) mitogen
      activated protein (MAP) kinase in fibroblasts. Ectopic expression of KSR
      inhibited the activation of ERK MAP kinase by insulin, phorbol ester, or
      activated alleles of Ras, Raf, and mitogen and extracellular-regulated kinase.
      Expression of deletion mutants of KSR demonstrated that the KSR kinase domain was
      necessary and sufficient for the inhibitory effect of KSR on ERK MAP kinase
      activity. KSR inhibited cell transformation by activated RasVal-12 but had no
      effect on the ability of RasVal-12 to induce membrane ruffling. These data
      indicate that KSR is a potent modulator of a signaling pathway essential to
      normal and oncogenic cell growth and development.

PMID- 9516484
TI  - Regulation of transforming growth factor-beta type II receptor expression in
      human breast cancer MCF-7 cells by vitamin D3 and its analogues.
AB  - In view of the tumor suppressor role of the transforming growth factor-beta
      (TGFbeta) type II receptor (RII), the identification and characterization of
      agents that can induce the expression of this receptor are of potential
      importance to the development of chemoprevention approaches as well as treatment
      of cancer. To date, the identification of exogenous agents that control RII
      expression has been rare. We demonstrated that proliferation of MCF-7 early
      passage cells (MCF-7 E), which express RII and are sensitive to TGFbeta growth
      inhibition activity, was significantly inhibited by vitamin D3 and its analogue
      EB1089. In contrast, proliferation of MCF-7 late passage cells (MCF-7 L), which
      have lost cell surface RII and are resistant to TGFbeta, was not affected by
      these two compounds. TGFbeta-neutralizing antibody was able to block the
      inhibitory effect on MCF-7 E cells by these compounds, indicating that treatment
      induced autocrine-negative TGFbeta activity. An RNase protection assay showed
      approximately a 3-fold induction of the RII mRNA, while a receptor cross-linking
      assay revealed a 3-4-fold induction of the RII protein. In contrast, there was no
      change in either RII mRNA or protein in the MCF-7 L cells.

PMID- 9516485
TI  - Regulation of the neurofibromatosis type 2 tumor suppressor protein, merlin, by
      adhesion and growth arrest stimuli.
AB  - The neurofibromatosis type 2 tumor suppressor gene is inactivated in the
      development of familial and sporadic schwannomas and meningiomas. The encoded
      protein, Merlin, is closely related to the Ezrin, Radixin, and Moesin family of
      membrane/cytoskeletal linker proteins. Examination of Merlin in several cell
      lines revealed that the protein migrates as two distinct species near 70 kDa.
      Phosphatase treatment and orthophosphate labeling demonstrated that the species
      with decreased mobility is phosphorylated. Given Merlin's localization to
      cortical actin structures, we examined the effect of cell-cell contact or other
      forms of growth arrest on Merlin expression and post-translational modification.
      Under conditions of confluency or serum deprivation, the levels of phosphorylated
      and unphosphorylated Merlin species increased significantly. Cells arrested in G1
      by other methods or other phases of the cell cycle did not show changes in Merlin
      levels. Furthermore, loss of adhesion resulted in a nearly complete
      dephosphorylation of Merlin, which was reversed upon re-plating of cells,
      suggesting Merlin phosphorylation may be responsive to cell spreading or changes
      in cell shape. Thus, the tumor suppressor function of Merlin may involve the
      regulation of cellular responses to cues such as cell-cell contact, growth factor
      microenvironment, or changes in cell shape.

PMID- 9516486
TI  - Reduced fertility in female mice lacking copper-zinc superoxide dismutase.
AB  - Copper-zinc superoxide dismutase (CuZn-SOD) is believed to play a major role in
      the first line of antioxidant defense by catalyzing the dismutation of superoxide
      anion radicals to form hydrogen peroxide and molecular oxygen. Recent studies
      have shown that missense mutations in this gene contribute, evidently through a
      gain-of-function mechanism, to about 20% of familial amyotrophic lateral
      sclerosis. To define further the physiologic role of this enzyme, a model of mice
      deficient in this enzyme was generated using gene targeting technology. Mice
      lacking this enzyme were apparently healthy and displayed no increased
      sensitivity to hyperoxia. However, they exhibited a pronounced susceptibility to
      paraquat toxicity. Most surprisingly, female homozygous knock-out mice showed a
      markedly reduced fertility compared with that of wild-type and heterozygous knock
      out mice. Further studies revealed that although these mice ovulated and
      conceived normally, they exhibited a marked increase in embryonic lethality.
      These data, for the first time, suggest a role of oxygen free radicals in causing
      abnormality of female reproduction in mammals.

PMID- 9516487
TI  - The overexpression of Bax produces cell death upon induction of the mitochondrial
      permeability transition.
AB  - Stably transfected Jurkat T cells were produced in which Bax expression is
      inducible by muristerone A. The cell death resulting from induction of the
      overexpression of Bax was prevented by inhibition of the mitochondrial
      permeability transition (MPT) with cyclosporin A (CyA) in combination with the
      phospholipase A2 inhibitor aristolochic acid (ArA). The caspase-3 inhibitor Z-Asp
      Glu-Val aspartic acid fluoromethylketone (Z-DEVD-FMK) had no effect on the loss
      of viability. The MPT was measured as the CyA plus ArA-preventable loss of the
      mitochondrial membrane potential (DeltaPsim). The MPT was accompanied by the
      release of cytochrome c from the mitochondria, caspase-3 activation in the
      cytosol, cleavage of the nuclear enzyme poly(ADP-ribose)polymerase (PARP), and
      DNA fragmentation, all of which were inhibited by CyA plus ArA. Z-DEVD-FMK had no
      effect on the loss of DeltaPsim and the redistribution of cytochrome c but did
      prevent caspase-3 activation, PARP cleavage, and DNA fragmentation. It is
      concluded that Bax induces the MPT, a critical event in the loss of cell
      viability. In addition to the cell death, the MPT mediates other typical
      manifestations of apoptosis in this model, namely release of cytochrome c,
      caspase activation with PARP cleavage, and DNA fragmentation.

PMID- 9516488
TI  - Grb2 and its apoptotic isoform Grb3-3 associate with heterogeneous nuclear
      ribonucleoprotein C, and these interactions are modulated by poly(U) RNA.
AB  - Grb2 is an adaptor molecule comprising one Src homology (SH) 2 and two SH3
      domains. This protein has a natural isoform named Grb3-3 with a deletion within
      the SH2 domain. Numerous evidence points to a functional connection between SH2-
      and SH3-containing proteins and molecules implicated in RNA biogenesis. In this
      context, we have examined the binding of Grb2 and Grb3-3 to heterogeneous nuclear
      ribonucleoprotein (hnRNP) C. By the use of an in vivo genetic approach and
      through in vitro experiments, we furnish evidence that both Grb2 and Grb3-3
      interact with hnRNP C proteins. Subcellular fractionation studies clearly show
      that Grb2 is partially localized in the nucleus. In addition,
      coimmunoprecipitation experiments demonstrate that Grb2.hnRNP C complexes exist
      in intact hematopoietic cells. The carboxyl-terminal SH3 domains of Grb2 and Grb3
      3 are primarily responsible for the association with hnRNP C. However, although
      the proline-rich motif of hnRNP C is involved in the interaction with Grb2, it is
      not in the binding to Grb3-3. Furthermore, poly(U) RNA inhibits the association
      of Grb2 with hnRNP C, whereas it enhances the interaction between Grb3-3 and
      hnRNP C. These findings suggest that the Grb2/Grb3-3-hnRNP C interactions might
      fulfill different biological functions.

PMID- 9516496
TI  - Mesenteric border linear ulcer in Crohn disease: historical, radiologic, and
      pathologic perspectives.

PMID- 9516495
TI  - Adult Crohn disease: can ileoscopy replace small bowel radiology?
AB  - BACKGROUND: This study aimed to document the radiological features and
      distribution of small bowel Crohn disease (CD) in adults by using a barium follow
      through (BaFT) technique and to determine whether disease would be missed or its
      distribution underestimated if only colonoscopy with ileoscopy were performed.
      METHODS: The BaFT examinations of 121 adults with proven CD were reviewed
      retrospectively with respect to the stage and distribution of disease.
      Colonoscopy with attempted ileoscopy was performed in 37 of these subjects, and
      the results were compared with radiological findings. RESULTS: A normal villous
      pattern was visualized in 89 studies (74%). BaFT showed small bowel CD in 71
      (59%) of 121 patients studied. The terminal ileum (TI) was the most common site
      of disease, affecting 62 (87%) of patients with small bowel CD. Forty-six
      patients (65%) had more proximal small bowel disease, including nine (13%) with a
      normal TI. BaFT showed early mucosal changes of CD in 52 subjects (73%), which
      was the sole manifestation in 15 (21%). Ileoscopy was possible in the majority of
      patients colonoscoped but was not achieved in 14 (38%), nine of whom had CD on
      BaFT. Of the 23 patients in whom ileoscopy was performed, findings agreed with
      BaFT assessment of the TI in 22. CONCLUSION: BaFT adequately demonstrates the
      stage and extent of small bowel CD. The majority of patients with small bowel CD
      have disease proximal to the TI, which cannot be diagnosed by ileoscopy.

PMID- 9516498
TI  - CT of large small-bowel diverticulum.
AB  - The previous reports concerning the computed tomographic (CT) appearances of
      small bowel diverticulum are usually limited to those of diverticulitis. We
      present the CT findings of uncomplicated, large small bowel diverticulum in five
      patients. An interesting coexistence of large small bowel diverticulum and small
      bowel volvulus will be mentioned. Four patients had recurrent abdominal pain in
      the past 2 years.

PMID- 9516497
TI  - Jejunal arteriovenous malformation, diagnosed by angiography and treated by
      embolization and catheter-guided surgery: case report and review of literature.
AB  - A case of chronic gastrointestinal hemorrhage caused by a small jejunal
      arteriovenous malformation (AVM) is reported. Treatment by endovascular
      embolization was temporarily successful. Subsequently, the patient underwent
      laparoscopic resection, guided by intraoperative catheter localization with
      methylene blue. Histopathology confirmed a true AVM. Eighteen months after
      treatment, the patient is free of symptoms. Literature of jejunal AVMs is
      reviewed.

PMID- 9516499
TI  - Adenocarcinoma arising in colonic duplication cysts with calcification: CT
      findings of two cases.
AB  - We report the computed tomographic findings of mucinous adenocarcinoma with
      calcification arising from duplication cyst of the colon in two adult cases. In
      both cases, serum levels of carcinoembryonic antigen (CEA) were high.
      Differential diagnosis of intraperitoneal or retroperitoneal cystic tumors with
      mucinous density includes duplication cyst, and its malignant change should be
      considered when serum level of CEA is high.

PMID- 9516500
TI  - Utility of flexible sigmoidoscopy as an adjunct to double-contrast barium enema
      examination.
AB  - BACKGROUND: There is controversy regarding the most appropriate investigation for
      suspected colorectal carcinoma. We offered these patients same-day flexible
      sigmoidoscopy (FS) and double-contrast barium enema (DCBE). METHODS: We reviewed
      the results of 117 consecutive adult patients. All patients underwent FS followed
      by DCBE on the same day. The radiographs were reviewed by two of the authors who
      were blinded to the clinical information, flexible sigmoidoscopy reports, and the
      original DCBE report. RESULTS: One hundred seventeen patients made up the study
      population. Thirty-four of the 117 patients had polyps and/or carcinoma. Three
      malignant tumours were detected by DCBE; one of these was also seen on FS, and
      the other two cancers were out of FS range. Fifty-three polyps were found by FS;
      nine were removed by biopsy prior to the enema examination. Of the 44 remaining
      polyps, DCBE failed to detect 87% of the 0-9-mm group and 67% of the >9-mm group.
      Ten polyps were seen only on DCBE; seven of these 10 were beyond the range of the
      sigmoidoscope, and the three remaining polyps were less than 5 mm. CONCLUSION:
      DCBE is insensitive in the detection of rectosigmoid polyps. FS should continue
      to be used as a complementary examination to DCBE in the investigation of
      suspected colorectal carcinoma.

PMID- 9516501
TI  - Prospective evaluation of colonic obstruction with computed tomography.
AB  - BACKGROUND: To determine whether computed tomography (CT) can satisfactorily
      diagnose and evaluate patients with suspected colonic obstruction. METHODS:
      Seventy-five patients with suspected colonic obstruction were evaluated
      prospectively by CT and compared with the gold standards of surgery and/or
      endoscopy in 65 patients, clinical course in nine, and contrast enema (CE) in
      one. A limited comparison between CT and CE (26) patients was also made in those
      patients who had both studies. RESULTS: CT successfully diagnosed colonic
      obstruction in 45 of 47 patients (96% sensitivity). Pseudo-obstruction was
      correctly diagnosed in 26 of 28 patients (93% specificity). CT correctly
      localized the point of obstruction in 44 of 47 patients (94%). CE successfully
      diagnosed obstruction in only 20 of 25 patients (80% sensitivity). CONCLUSION: In
      this study, CT proved to be a satisfactory modality in evaluating patients with
      suspected colonic obstruction. CT may in certain circumstances be preferable to
      the traditional CE in evaluating these patients.

PMID- 9516502
TI  - Abdominal CT in familial Mediterranean fever: a case report.
AB  - In order to clarify abnormal findings at abdominal ultrasound (suspicion of late
      abscess subsequent to appendectomy) in a young male patient with known familial
      Mediterranean fever (FMF), a helical CT examination of the abdomen was performed.
      At CT, extensive serositis of the lower abdomen was detected. Findings at CT were
      verified 2 weeks later at laparoscopy.

PMID- 9516503
TI  - Lobar atrophy of the liver.
AB  - Lobar atrophy of the liver due to causes other than liver tumor or liver
      cirrhosis is a relatively rare pathological condition, and there are only a few
      reports in the literature. We report six such cases and try to evaluate the
      relationship between lobar atrophy and portal flow disturbance. The patients
      could be divided into two groups according to the site of the atrophy: those with
      atrophy of the left lobe (two cases) and those with atrophy of the right lobe
      (four cases). The two cases with atrophy of the right lobe had hepatholithiasis
      in the involved segments, but the cause was not determined in the remaining four
      cases. In all six cases, portal flow disturbance was noted, including
      invisibility of the portal vein in four cases, narrowing in one case, and portal
      thrombus in one case. Collateral circulation was not recognized in any of our
      cases. Of interest is the mode of lobar atrophy. Atrophy of the right lobe was
      always associated with marked enlargement of the left lobe, but that of the left
      lobe did not induce an enlargement of the right lobe.

PMID- 9516504
TI  - Hepatic involvement in hypereosinophilic syndrome: value of portal venous phase
      imaging.
AB  - US, portal venous phase CT, and MRI-CSE (MRI with conventional spin-echo
      sequence) findings in three cases of hepatic involvement in hypereosinophilic
      syndrome are presented. These showed varied imaging findings, but portal venous
      phase CT showed multiple, poorly marginated, and hypodense hepatic lesions in all
      three cases. The result suggested that portal venous phase CT is the optimal
      method for depicting hepatic involvement.

PMID- 9516505
TI  - Magnetic resonance imaging of an angiomyolipoma of the liver.
AB  - A case of hepatic angiomyolipoma and its imaging features are presented. Computed
      tomography of the liver showed a low-density mass without obvious fat. T1
      weighted magnetic resonance images revealed a low-signal-intensity mass
      containing some tiny high-signal-intensity foci. One of the high-signal-intensity
      foci was found by histology to represent the fat component of the tumor.

PMID- 9516506
TI  - Fluid-fluid levels within focal hepatic lesions: imaging appearance and etiology.
AB  - PURPOSE: To report our experience with fluid-fluid levels within focal hepatic
      lesions and determine if this finding indicates a specific diagnosis. MATERIALS
      AND METHODS: We reviewed our experience with eight patients with focal hepatic
      lesions that showed fluid-fluid level on cross-sectional imaging. Seven CT scans,
      four MR examinations, and four sonograms were reviewed. The hepatic lesions
      included metastases (four patients), biliary cystadenoma (two patients),
      cavernous hemangioma (one patient), and hematoma (one patient). A histologic
      diagnosis was made in all cases. RESULTS: Fluid-fluid levels were found in both
      malignant and benign focal hepatic lesions. Fluid-fluid levels were seen on six
      CT scans, four MR examinations and on none of the four sonograms. Radiologic
      pathologic correlation showed that fluid-fluid levels corresponded to internal
      hemorrhage in all but one case. In the case of cavernous hemangioma, a fluid
      fluid level was found to correspond to a sedimentation effect within a large
      vascular space. CONCLUSION: Fluid-fluid levels in focal hepatic lesions do not
      indicate a specific diagnosis but can be seen in both malignant and benign
      conditions affecting the liver.

PMID- 9516508
TI  - CT imaging of biliary enteric fistula.
AB  - BACKGROUND: To define the signs useful for differentiating between gallbladder
      enteric fistula (GB-EF) and common bile duct-enteric fistula (CBD-EF) on computed
      tomography (CT) because the prognosis and management of the two are different.
      METHODS: CT scans in 13 patients with pneumobilia, who had not had surgical
      biliary-enteric anastomosis and endoscopic sphincterotomy, were reviewed. The
      presence of fistula itself, the location of air in the biliary system, and the
      appearance of the gallbladder were assessed. RESULTS: The causes of pneumobilia
      were GB-EF in seven patients, CBD-EF in three patients, emphysematous
      cholecystitis (EC) in one patient, gallbladder cancer (GBC) in one patient, and
      incompetent sphincter of Oddi in one patient. In three of seven GB-EF patients
      (43%) and in none of the three CBD-EF patients (0%), the fistula itself was
      detected. Air was detected in the common bile duct in four of seven GB-EF (57%)
      and in all three CBD-EF (100%) patients, and GBC. In six of seven GB-EF (86%) and
      in one of three CBD-EF (33%) patients, the gallbladder was contracted. Thus, the
      location of air and the contraction of gallbladder were useful signs to
      differentiate GB-EF from CBD-EF. CONCLUSION: CT can distinguish between GB-EF and
      CBD-EF.

PMID- 9516507
TI  - Intrahepatic venous collaterals.
AB  - BACKGROUND: The aim of this study was to reevaluate the causes and sites of
      intrahepatic venous collaterals and to determine the role of color Doppler
      sonography in the diagnosis of this relatively rare vascular abnormality.
      METHODS: Real-time color Doppler sonography was used to study 21 patients with
      intrahepatic venous collaterals. The cause, distribution, and clinical
      manifestations of collaterals were determined, and Doppler waveforms obtained
      from the collaterals were also analyzed. RESULTS: First, the causes of
      intrahepatic venous collaterals were divided roughly into two groups according to
      the presence or absence of veno-occlusions. The former group included liver
      tumors (six cases), primary Budd-Chiari syndrome (five cases), and metastatic
      adrenal tumors invading the inferior vena cava (two cases). The latter group
      consisted of diaphragmatic hernia (three cases), Osler-Weber-Rendu disease (two
      cases), and congestive liver (one case). The cause was not determined in two
      cases. Second, venous collaterals were distributed throughout the entire liver in
      primary Budd-Chiari syndrome but localized in the other cases. Third, Doppler
      waveforms of the collaterals were divided into two patterns: flat flow and
      multiphasic flow. Flat flow pattern was seen in patients with veno-occlusive
      diseases, and multiphasic flow pattern was seen in patients without veno
      occlusive disease. CONCLUSION: The relationship between intrahepatic venous
      collaterals and veno-occlusive diseases has been emphasized in the literature,
      but the results of our series showed that they occurred under a wide variety of
      conditions, even without veno-occlusive diseases, including diaphragmatic hernia
      and Osler-Weber-Rendu disease. The analysis of the Doppler waveforms of the
      collaterals was useful in differentiating those due to veno-occlusive diseases
      and those not.

PMID- 9516510
TI  - Portal vein calcification and associated biliary stricture in idiopathic portal
      hypertension (Banti's syndrome).
AB  - We present a case of dense portal vein calcification with secondary extrahepatic
      biliary stricture and cholangitis in an adult patient diagnosed with idiopathic
      portal hypertension at age three. Biliary ductal dilation proximal to echogenic
      shadowing foci near the porta hepatis mimicked choledocholithiasis on sonographic
      examination. Portal vein calcification and biliary stricture from portal
      venopathy each represent rare findings. The obstruction was successfully managed
      with biliary stenting.

PMID- 9516509
TI  - Obstructive jaundice caused by lymphangitis carcinomatosa of bile duct wall from
      gastric carcinoma.
AB  - We report a case of advanced gastric carcinoma presenting with obstructive
      jaundice. Computed tomography showed marked lymphadenopathy in the hepatoduodenal
      ligament and concentric bile duct wall thickening. Histologically, extrahepatic
      bile duct wall was thickened due to submucosal lymphangitic spread of gastric
      carcinoma (lymphangitis carcinomatosa). Lymphangitis carcinomatosa may be
      considered when extrahepatic bile duct wall thickening is seen in patients with
      obstructive jaundice.

PMID- 9516511
TI  - CT diagnosis of perihepatic endometriosis complicated by malignant
      transformation.
AB  - Endometriosis is a condition in which endometrial tissue becomes implanted on
      extrauterine sites, most commonly within the pelvis. Malignant transformation of
      endometriotic foci is rare, but has been frequently reported. We describe a
      patient with a CT scan demonstrating pathologically proven perihepatic
      endometriosis, including malignant transformation. Endometrioses should be
      considered in the differential diagnosis of perihepatic masses.

PMID- 9516512
TI  - Lymphoepithelial cysts of the pancreas: CT and sonographic findings.
AB  - Two cases of rare lymphoepithelial cyst (LEC) of the pancreas are presented.
      Although the histogenesis of this lesion is not known, it can be histologically
      differentiated from other pancreatic and retropancreatic cysts. The importance of
      its recognition is in the distinction from cystic neoplasm of the pancreas.

PMID- 9516513
TI  - Primary carcinoid tumor of the pancreas.
AB  - Serotonin-secreting (carcinoid) tumors of the pancreas are very rare. There are
      only 13 cases reported since 1963. Liver metastases have not previously been
      described. We present two patients with primary carcinoid tumor of the pancreas,
      which metastasized to the liver. These patients differ in their clinical and
      radiological appearance. Carcinoid tumor should be considered in the differential
      diagnosis of a pancreatic mass in a patient with carcinoid syndrome, but lack of
      this syndrome does not exclude the diagnosis.

PMID- 9516514
TI  - Intrapancreatic accessory spleen: case report.
AB  - We report a rare case of intrapancreatic accessory spleen which radiologically
      mimicked a pancreatic hypervascular tumor. The diagnosis of an intrapancreatic
      accessory spleen should be considered when a pancreatic mass has the CT densities
      and/or MR signal intensities similar to those of the spleen, with and without
      contrast medium.

PMID- 9516516
TI  - Focal splenic lesions in patients with AIDS: sonographic findings.
AB  - BACKGROUND: The purpose of this study was to describe the sonographic features of
      the focal splenic lesions in patients with AIDS and to know the frequency and
      etiology of these features. METHODS: Sonographic exams of 278 AIDS patients were
      reviewed retrospectively. We recorded the clinical indications for sonograms and
      sonographic findings of those patients with focal splenic lesions. In addition,
      patients' histories were reviewed to determine the etiology of such lesions.
      Ultrasound exams were performed with a 3.5-MHz transducer. RESULTS: Sonography
      demonstrated focal splenic lesions in 22 patients (7.9%). Eighteen patients
      (81.8%) showed small, multiple, hypoechoic, rounded splenic lesions; one patient
      had a solitary defect with similar features. In these 19 patients (86.3%),
      splenic lesions were due to disseminated Mycobacterium tuberculosis infection.
      One case showed two large hypoechoic wedge-shaped lesions that were splenic
      infarctions secondary to acute bacterial endocarditis. In two patients (9%) with
      solitary and multiple small hypoechoic lesions, the cause of the lesions remained
      unknown. All patients had splenomegaly. Hepatomegaly with focal lesions,
      retroperitoneal lymphadenopathy, or ascites were also seen. CONCLUSION: In our
      area, the finding of splenomegaly with small, multiple, hypoechoic lesions in
      AIDS patients should make clinicians suspect splenic tuberculosis as a first
      possibility.

PMID- 9516515
TI  - Torsion of a wandering accessory spleen: CT findings.
AB  - Torsion of an accessory spleen is a rare entity that can have a variable clinical
      presentation. We report the computed tomographic (CT) findings of an acute
      torsion of an accessory spleen in a 13-year-old girl. CT disclosed a hypodense
      mesenteric mass with peripheral inflammatory changes.

PMID- 9516517
TI  - Peliosis of the spleen: splenic rupture with intraperitoneal hemorrhage.
AB  - Peliosis is a rare disease that is characterized by multiple blood-filled cystic
      spaces. We report the computed tomographic findings of splenic rupture secondary
      to splenic peliosis in a patient receiving anabolic steroids for aplastic anemia.

PMID- 9516518
TI  - Renal squamous cell carcinoma: CT findings and clinical significance.
AB  - BACKGROUND: To study the biological behavior of renal squamous cell carcinoma
      (RSCC). METHODS: Fifteen cases of RSCC were retrospectively studied. These cases
      were classified as central (eight cases) and peripheral (seven cases) types by
      the tumor location. The clinical data and computed tomographic findings were
      analyzed and compared. RESULTS: High incidence (87%) of urolithiasis was
      observed. The prognosis of RSCC was very poor, with a median survival time of 3.5
      months. The infectious symptoms, central location, and modified stage IV of the
      tumor were the poor prognostic factors of RSCC. Two types of RSCC were different
      in the presenting symptoms, lymph node metastasis, modified tumor staging, and
      survival time. CONCLUSION: The central and peripheral types of RSCC were
      different biologically. High index of suspicion should be maintained when
      identifying the subtle clues of malignancy in patients with urolithiasis.

PMID- 9516519
TI  - Percutaneous renal hydatid cyst treatment: long-term results.
AB  - BACKGROUND: To evaluate the effectiveness of percutaneous treatment of renal
      hydatid cysts. METHODS: Four male and one female (14-52 years old, mean = 37
      years) patients with five renal cysts were treated percutaneously. All five cysts
      from the patients were pure fluid collections, which were consistent with type I
      hydatid cysts according to Gharbi's classification. After entering the cystic
      cavity under sonographic guidance, cystic fluid was aspirated, and the cavity was
      filled with hypertonic saline (15% NaCl). In three patients with cysts larger
      than 6 cm in diameter, catheterization was performed under fluoroscopic guidance,
      and the cavity was filled with 95% absolute alcohol to sclerotize the cyst walls.
      In two patients with cysts smaller than 6 cm in diameter, the procedure was
      carried out by a technique in which the cyst was puncture aspirated, hypertonic
      saline solution was injected, and the cyst was reaspirated. The patients were
      followed by ultrasonography and computed tomography. Follow up was 5-62 months
      (mean = 33.8 months). RESULTS: Sonographic follow-up examinations indicated a
      gradual decrease in cyst size and volume. The size reduction was significant (p <
      0.05). The volume reduction rate was 55-95% (mean = 81%). During follow up, fluid
      components of all five cysts reduced gradually and finally disappeared, leaving a
      remnant that is called a "pseudotumor appearance." Neither mortality nor any
      dissemination was encountered during follow up. The only complication seen in
      this series was an abscess that was successfully treated with percutaneous
      drainage. CONCLUSION: According to the results of our study, percutaneous
      treatment of renal hydatid cysts avoids the morbidity of open surgery and
      preserves the residual function of the kidney.

PMID- 9516520
TI  - Uterine lipoleiomyoma: MRI appearances.
AB  - A case of uterine lipoleiomyoma demonstrated on computed tomography (CT) and
      magnetic resonance imaging (MRI) is described and usefulness of MRI is discussed
      in diagnosing this entity.

PMID- 9516521
TI  - Corkscrew esophagus: elongation?

PMID- 9516522
TI  - Development of colon length, musculature, and haustration after birth and
      associated malformations.

PMID- 9516523
TI  - Abstracts of selected papers from the current literature

PMID- 9516526
TI  - PROFILE: River Dolphins in Bangladesh: Conservation and the Effects of Water
      Development
AB  - / Ganges river dolphins (Platanista gangetica) are threatened in Bangladesh from
      the effects of dams, large embankment schemes, dredging, fisheries bycatch,
      directed hunting, and water pollution. Visual surveys of the section of the
      Jamuna River located between the divergence of the Old Brahmaputra River and the
      confluence of the Padma River and the section of the Kushiyara River located
      between the Bangladesh-India border and the confluence of the Korangi River
      recorded a sighting rate of 0.13 sightings/km (mean group size = 1.8 dolphins)
      and 0.08 sightings/km (mean group size = 3.8 dolphins), respectively. These
      sections of river were considered to be priority areas for investigation because
      several water development projects have already been constructed and more are
      planned for the areas. During the surveys we examined the remains of dolphins
      caught accidentally in plastic gillnets and observed fishermen catching the fish
      species Clupisoma garua using dolphin oil and body parts as a fish attractor.
      Additional studies are needed to assess the status of dolphins and effects of
      water development and fisheries bycatch. Feasibility studies should be conducted
      on designating dolphin/fish sanctuaries and creating artificial habitat or
      enhancing existing habitat in eddy countercurrent scour pools to mitigate
      deleterious impacts. The environmental requirements of river dolphins reflect the
      needs of productive and biotically diverse tropical rivers.KEY WORDS: Bangladesh;
      River dolphins; Water development; Platanista; Fisheries bycatch; Flood Action
      Plan; Dams; Embankments; Barrages

PMID- 9516527
TI  - Evaluating Management of Protected Areas: Integrating Planning and Evaluation
AB  - / An approach to evaluating the effectiveness of management of protected areas is
      proposed. This approach has been used in developing an evaluation strategy for
      the Fraser Island World Heritage Area in Australia. The main component of the
      strategy is built upon the desired outcomes specified in the management plan for
      the area and thus provides a basis for assessing the extent to which the plan's
      objectives are being achieved. A series of monitoring programs have been proposed
      to enable this assessment. Examples of monitoring programs developed as part of
      the evaluation strategy are presented. A second component of the strategy
      monitors the implementation of the management plan. A management information
      system has been developed to record and report on the extent to which the
      specific actions specified in the management plan have been implemented. The
      strategy is discussed in relation to seven objectives set for the evaluation
      program in its design phase.KEY WORDS: Planning; Evaluation; Monitoring;
      Management; Protected areas

PMID- 9516528
TI  - Environmental Values and Popular Conflict over Environmental Management: A
      Comparative Analysis of Public Comments on the Clinton Forest Plan
AB  - / Public participation in environmental management decisions has frequently led
      to conflict. This paper examines the role of environmental values in fueling
      these conflicts, based on a data base and sample content analysis of written
      public comments solicited in 1994 regarding the highly contentious Clinton Forest
      Plan (also known as Option 9) proposed for management of federal forests in the
      US Pacific Northwest. The analysis considered whether those respondents favoring
      more versus less environmental protection than was offered in Option 9 held
      entirely different values, identifying which antagonistic values appeared to be
      most fundamental and where (if at all) values consensus occurred. It also
      compared values emanating from respondents within and outside the affected
      region, although few major differences were detected in this regard. Results
      suggest that strong values differences did exist among those preferring greater
      versus less environmental protection, in particular as concerned the extent,
      form, and spatial and temporal scope of justification of their positions, their
      ideas of forests, and the appropriate role of people in forest management.
      Disagreement concerned far more than purely environmental values: a major point
      of difference involved human benefits and harms of the proposed forest plan.
      Indeed, both sides' positions were overridingly anthropocentric and
      consequentialist-a values orientation that almost inevitably spells conflict in
      light of the commonly differentiated social impacts of environmental management
      decisions. Although public involvement in environmental management thus cannot be
      expected to lead to a clear and consensual social directive, the Pacific
      Northwest case suggests that viable environmental management solutions that take
      this range of values into account can still be crafted.KEY WORDS: Environmental
      values; Public participation; Clinton Forest Plan; Pacific Northwest

PMID- 9516529
TI  - Socioeconomic and Institutional Dimensions of Dam Removals: The Wisconsin
      Experience
AB  - / There are tens of thousands of small dams in the United States; many of these
      aging structures are deteriorating. Governments and dam owners face decisions
      regarding repair or removal of these structures. Along with the many benefits
      society derives from dams and their impoundments, numerous recent ecological
      studies are revealing the extensive alteration and degradation of river
      ecosystems by dams. Dam removal-a principal restoration strategy-is an infrequent
      event. The major reasons for removal have been public safety and the high costs
      associated with repair; the goal of river ecosystem restoration now warrants
      greater attention. Substantial study is being given to the environmental aspects
      of dams and dam removals, but very little attention has been given to the
      socioeconomic and institutional dimensions associated with the removal of dams,
      although these factors play a significant role in the removal decision-making
      process. Based on a case study of dam removals in Wisconsin-where more than 30 of
      the state's 3600 small dams have been removed in the past few decades-legal,
      financial, and socioeconomic issues associated with dam removal are documented
      and assessed. Dam removal has been complex and contentious, with limited
      community-based support for removal and loss of the impounded waters. In cases
      examined here, the estimated costs of repairing a dam averaged more than three
      times the cost of removal. The availability of governmental financing has been a
      key determinant in removal decisions. Watershed-scale ecological considerations
      are not major factors for most local interests. As watershed management and
      restoration increasingly include dam removal options as part of an integrated
      strategy, more attention will need to be focused on socioeconomic factors and
      stakeholder perspectives-variables that strongly influence the viability of this
      management alternative.KEY WORDS: Dam removal; River restoration; Institutions;
      Stakeholders

PMID- 9516531
TI  - Regulation of Hillside Development in the United States
AB  - / This paper examines the range of issues concerning hillside development in the
      United States. Hillside development is regulated for a variety of reasons:
      aesthetics, public safety, and environmental quality. Sometimes these reasons
      conflict. In part this reflects differing views among the design and construction
      disciplines: architects, engineers, engineering geologists, landscape architects,
      and planners. This paper presents a history of hillside planning, lays out some
      of the differing points of view, and summarizes the contents of hillside plans
      and ordinances collected from 190 local governments throughout the United States.
      The documents reflected a variety of purposes. Thirty-four specific purposes were
      identified, and 43% of the documents identified five or more purposes. Most
      ordinances emphasize protection of scenic quality (75%) and natural phenomena
      (71%), with a significant number also promoting public safety (64%). The study
      also identified 31 specific implementation strategies to achieve those goals. On
      the one hand, this study shows a rich variety of goals, policies, and strategies
      for managing hillside development. It is possible, however, that many of them
      accept, without resolving, the conflicting professional views toward hillside
      development management.KEY WORDS: Land-use planning; Hillside development;
      Hillside regulation

PMID- 9516530
TI  - Contemporary Western Rural USA Economic Composition: Potential Implications for
      Environmental Policy and Research
AB  - / The rural West of the United States is considered strongly antienvironment. The
      traditional economic reliance of the area on natural resources has long explained
      this antienvironment stance. The region consistently elects federal officials who
      as a group consistently vote against environmental bills and seek to undo
      existing federal environmental regulation. These politicians defend their
      antienvironment actions based on their perception of the economic composition and
      interests of the region. Recent studies, however, have suggested that rural
      residents are increasingly concerned about environmental issues. These studies,
      however, lack a consistent theoretical basis. This article uses an alternative
      economic typing system to examine the economic composition of rural Idaho and
      suggests that the results found using the alternative typing system might provide
      a theoretical basis to explain why some studies are finding increased rural
      environmental support. The results show that rural Idaho is much more
      economically diverse using this alternative typing methodology compared to the
      outcomes of traditional USDA economic methodologies. The policy and research
      implications of these findings are examined.KEY WORDS: Rural; Environmental
      policy; Economic composition

PMID- 9516532
TI  - Processes in Pollution Management: An Australian Model
AB  - / This paper describes a model of the social and institutional processes involved
      in the solution of major pollution problems from the time they are first
      identified until they are resolved. The model is empirically demonstrated using
      four case studies of water and air pollution problems from Sydney, New South
      Wales, Australia. Each process of the model is quantified by the use of an
      indicator, e.g., number of articles in newspapers to measure the process
      "publicconcern," number of pages of text devoted to parliamentary debates to
      measure the process "political action." The case study data are presented on a
      time-line graph that shows the duration and magnitude of each process. The paper
      illustrates three aspects of the solution of major pollution problems: the long
      time frames involved, the importance of public opinion in initiating the solution
      process, and the partial nature of solutions-problems may be politically resolved
      but often a complete solution is not achieved. An understanding of social and
      institutional processes and time frames will enable planners and policy makers to
      communicate to the public and politicians the consequences of delay in acting to
      solve pollution and to direct attention to critical areas to expedite
      solutions.KEY WORDS: Pollution problems; Management process model; Performance
      indicators; Air pollution; Water pollution

PMID- 9516533
TI  - Effect and Control of Pollution in Catchment Area of Lake Sapanca, Turkey
AB  - / Land-based point and diffuse pollution sources in the catchment area of Lake
      Sapanca, Turkey, were investigated. The present and future distribution of
      pollution loads were evaluated in terms of nitrogen, phosphorus, biochemical
      oxygen demand, and pesticides. A methodology for the estimation of pollution
      loads was presented; most of which were based on "unit loads." Presently domestic
      and industrial point sources dominate over diffuse sources including fertilizers
      and pesticides from agricultural use, nutrient loads from forests and meadows,
      urban runoff, and leachates from unregulated dumps of solid wastes. For the
      future, the aim of the control action is to maintain the sustainability of the
      water quality of the lake, at least at the second class of European Community
      standards. Within this framework; urgent/short-term and medium/long-term control
      actions will be exercised. In the urgent/short-term stage, simpler and natural
      ways of treatment will be employed. In the medium/long-term stage an integrated
      collection and treatment system will be put on operation. After completion of a
      proposed collection system and treatment plants to handle point sources, the
      control of diffuse sources will be more significant. Control of diffuse sources
      for the abatement of further deterioration of water quality then becomes the key
      issue to be emphasized in the Lake Sapanca catchment area. Diffuse sources
      control will be achieved by dividing the catchment area into three major
      protection zones. Use of pesticides and fertilizers on agricultural land and all
      other activities within these protection zones will be accomplished according to
      control plans, which will be supervised by an institution established to be
      responsible of all the activities within the basin.KEY WORDS: Diffuse sources;
      Land-based pollution; Nutrients; Pesticides; Point sources; Protection zones

PMID- 9516534
TI  - RESEARCH: Physicochemical Characteristics and Pollution Indicators in the
      Intertidal Zone of Kuwait: Implications for Benthic Ecology
AB  - / The coastal environment of Kuwait has been under considerable stress since the
      onset of the oil era in the late 1950s and early 1960s. Oil, sewage, and
      industrial pollution were believed to be the main environmental problems in the
      coastal zone. The huge oil spill and destruction caused by the Gulf War further
      complicated those problems. In this article, the temperature, pH, salinity, and
      total dissolved sulfide (TDS) of the interstitial water in the intertidal zone
      and the water content and total organic carbon (TOC) of the intertidal sediment
      were investigated. The purpose of the study was to understand the effect of the
      physicochemical characteristics on the intertidal benthic ecology and to identify
      the level and sources of organic pollution in the intertidal zone. The study
      results indicated that the prevailing harsh environmental conditions, especially
      high temperature and salinity, restricted benthic fauna diversity and led to the
      development of a fragile intertidal ecosystem. The fauna inhabiting the
      intertidal zone was dominated by a few species probably living at their limit of
      tolerance. Organic pollution was evident mainly in Sulaibikhat Bay and to a
      lesser extent in Kuwait City waterfront and Shuaiba coast in the south. The
      pollution was attributed mainly to land-based sources such as the occasional
      discharge of raw sewage through stormwater outlets, the direct oil spillage, and
      industrial effluents from refineries, oil terminals, and petrochemical plants.
      Quantitative analysis was inconclusive in establishing a significant correlation
      between the chemistry and composition of the benthic fauna. However, close
      examination of sites with high TOC and TDS concentrations indicated that the
      benthic fauna in those sites was showing evidence of degradation. A number of
      strategies were recommended to ensure protection and sustainable management of
      the coastal environment.KEY WORDS: Intertidal environment; Pollution; Total
      organic carbon; Dissolved sulfide; Interstitial water; Benthic fauna

PMID- 9516535
TI  - Fish Community Structure as a Measure of Degradation and Rehabilitation of
      Riparian Systems in an Agricultural Drainage Basin
AB  - / Assessing the health of ecological components of agroecosystems may be
      accomplished by examining changes in the drainage basin, which serves as an
      integrator of the agroecosystem landscape. In this study we examined fish
      communities in terms of an array of indicators of structure and related these to
      changes in riparian vegetation and agricultural practice. Evidence suggests
      management practices designed to foster healthier environments by, for example,
      reestablishing riparian vegetation were associated with positive impacts on the
      integrity of the fish community. At the same time, continued intensification of
      agricultural practices in parts of the drainage basin in recent years likely has
      had an off-setting influence in overall improvements in agroecosystem health.
      Assessments of changes in the structure of the fish associations provide the
      balance sheet by which the counteracting influences can be aggregated and
      assessed.KEY WORDS: Fish community structure; Riparian system; Agricultural
      drainage basin

PMID- 9516536
TI  - Macroinvertebrate Community Structure Along the Longitudinal Gradient of an
      Agriculturally Impacted Stream
AB  - / Lapwai Creek, an agriculturally impacted stream in northern Idaho, was sampled
      seasonally over a two-year period to determine if macroinvertebrate community
      composition changed along the longitudinal gradient and if changes followed
      predictions of the river continuum concept. Possible relationships between
      changes in food resource availability and community structure were also examined.
      Benthic invertebrates were collected at eight locations along the longitudinal
      gradient of Lapwai Creek using a Hess sampler. Random skewer analysis suggested
      there was no longitudinal gradient for either number of individuals or functional
      feeding group composition. Cluster analysis revealed that all locations,
      excluding a site receiving outflow from a small, eutrophic reservoir, had a
      similar community structure, further suggesting that invertebrate community
      composition remained consistent along the longitudinal gradient of the stream.
      The community was dominated at all sites, excluding the site below the reservoir,
      by functionalgrazers. Shredders were rare throughout Lapwai Creek, even in areas
      where healthy riparian vegetation still remained. Studies of other streams within
      the drainage basin show that many species found in the upper reaches of these
      streams, where agricultural impacts are low, were absent throughout the length of
      Lapwai Creek. Data collected concurrently with macroinvertebrates indicated that
      the input, storage, and transport of particulate organic matter was low
      throughout the stream, whereas periphyton abundance was high. The absence of
      longitudinal changes, despite flowing through three distinct geomorphological
      regions, and the grouping of all sites except one by cluster analysis for both
      dominant taxa and functional feeding groups suggest that agricultural alteration
      has influenced community structure of Lapwai Creek, resulting in a relatively
      homogeneous assemblage of macroinvertebrates capable of tolerating agricultural
      nonpoint source pollution. Additional support for this hypothesis is the high
      abundance of one food source, periphyton, and the small quantities of
      terrestrially derived organic matter. The abundance of the former and the rarity
      of the latter can be attributed to alteration of the drainage basin resulting
      from agricultural activities through inputs of fertilizers that generated high
      nutrient concentrations and the removal of riparian vegetation to clear more land
      for agriculture and provide increase access to the stream.KEY WORDS: Agriculture;
      Longitudinal patterns; Macroinvertebrates; Nonpoint source; River continuum

PMID- 9516537
TI  - Evaluating the Role of Plantations as Carbon Sinks: An Example of an Integrative
      Approach from the Humid Tropics
AB  - / Despite their fast growth, tropical plantations are a small sink of atmospheric
      carbon because they occupy only a small area in relation to other land uses
      worldwide. Proper design and management of plantations can increase biomass
      accumulation rates, making them more effective C sinks. However, fast-growing
      plantations can extract large amounts of nutrients from the soil, and site
      fertility declines may limit sustained plantation forestry after a few rotations.
      We measured aboveground biomass accumulation, carbon sequestration, and soil
      chemistry in three young plantations of 12 indigenous tree species in pure and
      mixed designs in the humid lowlands of Costa Rica. Annual biomass increments for
      the three mixed plantations ranged from 10-13 Mg/ha. The mixtures of four species
      gave higher biomass per hectare than that obtained by the sum of one fourth
      hectare of each species in pure plots. At this early age of the plantations,
      estimated annual C sequestration values were comparable to other reports from
      young plantations of exotic species commonly grown in the tropics. Four years
      after planting, decreases in soil nutrients were apparent in pure plots of some
      of the fastest growing species, while beneficial effects on soils were noted
      under other species. The mixed plots showed intermediate values for the nutrients
      examined and, sometimes, improved soil conditions. A mixture of fast and slower
      growing species yields products at different times, with the slower growing
      species constituting a longer term sink for fixed carbon. Examination of the role
      of tropical plantations as C sinks necessitates integrative approaches that
      consider rates of C sequestration, potential deleterious effects on ecosystem
      nutrients, and economic, social, and environmental constraints.KEY WORDS: Native
      trees; Aboveground biomass; Stem increments; Rotation length; Soil nutrients;
      Economics

PMID- 9516538
TI  - Window Sensitivity Functions for Line Transect Sampling
AB  - / The estimation of animal or plant abundance by the line or belt transect
      sampling method has been investigated by many authors, including biologists,
      statisticians, biometricians, wildlife scientists, and fisheries and forestry
      specialists. The method has reached wide acceptance over the last 30 years, and
      the theoretical development has continued to expand, both from a parametric and a
      nonparametric point of view. This article examines the line transect sampling
      method from a slightly different perspective. If the line transect region is
      regarded as a rectangle with length L and width 2w, then by a selection of
      viewing window is meant a choice of w, with the intent being to search for
      optimal viewing windows, with the goal in mind of improving variances of
      estimators of population density, reducing sampling effort, while maintaining the
      property of unbiasedness. The notions of increasing window sensitivity (IWS) and
      decreasing window sensitivity (DWS) are introduced, and a method of deriving
      confidence intervals is discussed.KEY WORDS: Line transection sampling;
      Population estimation; Probability detection function; Window sensitivity
      function; Strip census.

PMID- 9516539
TI  - Evidence for arylamine N-acetyltransferase activity in the Escherichia coli.
AB  - N-Acetyltransferase activities with p-aminobenzoic acid and 2-aminofluorene as
      substrates were determined in isolates of the bacterium Escherichia coli. The N
      acetyltransferase activity was determined by an acetyl CoA recycling assay and
      high pressure liquid chromatography. The N-acetyltransferase activities from a
      number of E. coli isolates were found to be 0.67 +/- 0.04 nmole/min/mg protein
      for 2-aminofluorene, and 0.46 +/- 0.02 nmole/min/mg protein for p-aminobenzoic
      acid. The apparent Km and Vmax values obtained were 2. 85 +/- 0.65 mM and 7.51 +/
      0.86 nmol/min/mg protein, respectively, for 2-aminofluorene, and 2.35 +/- 0.39
      mM and 9.43 +/- 0.78 nmol/min/mg protein, respectively, for p-aminobenzoic acid.
      The optimal pH value for the enzyme activity was 7.0 for both substrates tested.
      The optimal temperature for enzyme activity was 37 degrees C for both substrates.
      The N-acetyltransferase activity was inhibited by iodoacetamide: at 0.25 mM
      iodoacetamide, activity was reduced 50%, and at 1.0 mM, more than 90%. Among a
      series of divalent cations and salts, Cu2+ and Zn2+ were demonstrated to be the
      most potent inhibitors. This report is the first demonstration of acetyl
      CoA:arylamine N-acetyltransferase activity in E. coli.

PMID- 9516540
TI  - Comparison of different methods of cell lysis and protein measurements in
      Clostridium perfringens: application to the cell volume determination.
AB  - Four cell lysis methods (NaOH-SDS solubilization, French press treatment,
      sonication, mutanolysin treatment) and three methods of protein assays (Lowry,
      Bradford, Pierce) were studied for their applicability to determination of cell
      volume in Clostridium perfringens NCTC 8798 cell suspensions. Protein contents
      were higher after a mechanical disruption of the cells than with the other
      techniques of lysis. The lowest concentrations of protein were obtained with the
      Bradford procedure. With each of the three protein assay methods, Clostridium
      perfringens NCTC 8798 protein cell contents were 45% to 58% of protein. Other
      factors possibly involved in variations of the intracellular volume measurements
      were examined. A control of the level of protein concentration in the test sample
      and the type of silicone oil used for the centrifugation were of prime importance
      during sample preparation. Under our conditions, an intracellular volume of 4
      microl/(mg of protein) was routinely found for Clostridium perfringens NCTC 8798.

PMID- 9516541
TI  - Microbial growth in a steady-state model of ethylene glycol-contaminated soil.
AB  - Biodegradation of ethylene glycol was tested in a laboratory-scale, steady-state
      infiltration system of two arid region soil types by monitoring indigenous
      microbial growth after the infiltration of three concentrations of ethylene
      glycol. Microorganisms in the soils were able to adapt to the ethylene glycol in
      several cases, resulting in higher numbers of microorganisms and lower pHs in the
      effluents. These microorganisms were identified and were able to use ethylene
      glycol as a sole carbon source. The adaptation was seen best with high-moisture
      content soils when the ethylene glycol concentrations were 1% or 10%. However,
      acclimation to 0.1% and 10% ethylene glycol did not occur in low-moisture-content
      clay soil, but did occur in low-moisture-content silt soil, indicating that soil
      type and moisture content are important factors. In all cases, microbial
      diversity decreased over time.

PMID- 9516542
TI  - Psychrotrophic bacteria isolated from a constantly warm tropical environment.
AB  - Psychrotrophic bacteria are known to occur in temperate, constantly cold, and
      artificially cooled environments. This is the first report of their occurrence in
      a constantly warm (ca. 24 degrees-35 degrees C) tropical environment. Soil
      samples taken from two sites along the southeastern coastal zone of Jamaica
      yielded growth of psychotrophic bacteria after 3-4 weeks of enrichment culture in
      1/30 strength tryptic soy broth, 20 mg L-1 cycloheximide at 2 degrees C. Growth
      of individual isolates at 2 degrees C was confirmed. Isolates include aerobic and
      fermentative Gram-negative rods and sporeforming (Bacillus sp.) and non
      sporeforming (Aureobacterium sp.) Gram-positive rods. We determined the effect of
      temperature on growth rate in four isolates. Strain Y1 has an unusually wide
      temperature range for growth, 2 degrees-44 degrees C, resembling that of Listeria
      monocytogenes. In strain R1 the optimum temperature for growth occurred unusually
      near the maximum temperature for growth. Strains R2 and Y2 displayed cardinal
      temperatures typical of known psychotrophs but appear to have evolved enhanced
      growth potential near the optimum temperature in response to a constantly warm
      environment.

PMID- 9516543
TI  - A sandwich enzyme-linked immunosorbent assay for the Bacillus sphaericus binary
      toxin.
AB  - Bacillus sphaericus (Bs) binary toxin was purified from recombinant E. coli
      DH5alpha harboring the recombinant plasmid pAR5, which carries a 3.6-kb DNA
      fragment of Bs 1593M encoding mosquito larvicidal activity. The binary toxin
      preparation, designated BsEcAg, contained mainly 51- and 42-kDa toxin proteins
      and was toxic to 50% of Culex quinquefasciatus larvae at a concentration of 9.22
      ng toxin protein/ml. This preparation was used to raise antibodies in sheep and
      mice. The sandwich ELISA used sheep antitoxin antibody as primary antibody
      (coating antibody), mouse antitoxin antibody as second antibody, and goat
      antimouse antibody as an alkaline phosphatase-conjugated detecting antibody. The
      assay sensitivity was 200 ng/ml for both BsEcAg and binary toxin antigen (BsAg)
      from Bs 2362 cells. There is a significant correlation between toxin level
      determined by ELISA and bioassay. This procedure has also been used to monitor
      toxin levels in batch fermentations of Bs 2362.

PMID- 9516544
TI  - Sequence analysis of a 34.7-kb DNA segment from the genome of Buchnera aphidicola
      (endosymbiont of aphids) containing groEL, dnaA, the atp operon, gidA, and rho.
AB  - Buchnera aphidicola is a prokaryotic endosymbiont of the aphid Schizaphis
      graminum. From past and present nucleotide sequence analyses of the B. aphidicola
      genome, we have assembled a 34. 7-kilobase (kb) DNA segment. This segment
      contains genes coding for 32 open reading frames (ORFs), which corresponded to
      89.9% of the DNA. All of these ORFs could be identified with homologous regions
      of the Escherichia coli genome. The order of the genes with established functions
      was groELS-trmE-rnpA-rpmH-dnaA-dnaN-gyrB-atpCDGAH FEB-gidA-fdx-hscA- hscB-nifS
      ilvDC-rep-trxA-rho. The order of genes in small DNA fragments was conserved in
      both B. aphidicola and E. coli. Most of these fragments were in approximately the
      same region of the E. coli genome. The latter organism, however, contained many
      additional inserted genes within and between the fragments. The results of the B.
      aphidicola genome analyses indicate that the endosymbiont has many properties of
      free-living bacteria.

PMID- 9516545
TI  - Flies and their bacterial loads in greyhound dog kennels in Kansas.
AB  - Breeders of greyhound dogs traditionally feed racing animals and nursing bitches
      raw meat, and that meat generally is obtained frozen from commercial renderers.
      Previous studies have shown that the rendered meat is frequently contaminated
      with enteric bacteria, including Salmonella spp., and that during thawing the
      rendered meat is exposed to filth flies common in dog kennels. Nursing greyhound
      pups tend to experience a high morbidity and mortality from intestinal
      infections, and we attempted to determine in this study whether enterics could be
      spread to pups through contaminated flies. At intervals during 1995 and 1996,
      flies were trapped or were net-collected from 10 dog breeding kennels in the
      region around Abilene, KS. Trapped flies were identified and counted to determine
      population numbers, and netted flies were cultured in tetrathionate broth and
      streaked to medium selecting for Salmonella sp. and other lactose-negative Gram (
      ) bacteria. The relative numbers of different fly species varied with the
      sampling method, but traps and sweep nets produced similar proportions of the
      different fly species. Blow flies were twice as likely to be contaminated with
      enteric bacteria as any other fly. The most common enteric bacteria found were
      Proteus spp., followed by Providencia spp., Pseudomonas spp., and Salmonella spp.
      The incidence of Salmonella and Proteus spp. seemed to correlate more with
      accessibility of flies to dog excrement than to rendered meat. The apparent high
      incidence of enteric contamination of filth flies clearly implicates them as
      vectors of enteric diseases in kennels.

PMID- 9516546
TI  - A new approach to separate the genus Photobacterium from Vibrio with RFLP
      patterns by HhaI digestion of PCR-amplified 16S rDNA.
AB  - A new approach to separate members of the genus Photobacterium from the genus
      Vibrio with RFLP (Restriction Fragment Length Polymorphism) patterns by HhaI
      digestion of PCR-amplified 16S rDNA was developed in the present study. It was
      clearly shown that these patterns of the genus Photobacterium were unique and
      distinguishable from Vibrio species. This method is very simple and does not need
      other supporting procedures, such as Southern transfer and probe hybridization.
      It can be applied not only to luminous species, but also to non-luminous
      Photobacterium spp. This result promises a rapid tool to distinguish the genus
      Photobacterium from Vibrio and should be useful in routine identification system.

PMID- 9516547
TI  - Susceptibility of the coffee leaf miner (Perileucoptera spp.) to bacillus
      thuringiensis delta-endotoxins: A model for transgenic perennial crops resistant
      to endocarpic insects 
AB  - Binding of several Bacillus thuringiensis delta-endotoxins was studied on
      histological midgut sections of larvae of coffee leaf miner Perileucoptera
      coffeella from Brazil and Perileucoptera sp from Madagascar. CryIA(a), CryIA(b),
      CryIA(c), CryIB, CryIE, and CryIIA were tested for binding, and only CryIA(c),
      CryIB, and CryIE yielded a positive response. The toxins bound to the whole
      midgut, and the result was identical on both insect populations. The same toxins,
      to the number of which CryIC was added, were tested on larvae of P. coffeella.
      CryIA(c) and CryIB were toxic with an LC50 of 1.47 &mgr;g/ml and 21.93 &mgr;g/ml,
      respectively. CryIE was not toxic to P. coffeella. CryIA(c) and CryIB were tested
      for synergistic activity and were shown to act by cumulative effect when
      delivered to the insect larvae as a mixture.

PMID- 9516549
TI  - Guidelines for laparoscopic surgery during pregnancy

PMID- 9516548
TI  - Guidelines for surgical treatment of gastroesophageal reflux disease (GERD)

PMID- 9516551
TI  - News and notices

PMID- 9516550
TI  - Guidelines for office endoscopic services

PMID- 9516552
TI  - Preface 
AB  - No Abstract Copyright

PMID- 9516553
TI  - Laparoscopic cholecystectomy.
AB  - Historically, cholelithiasis in children was thought to develop secondary to
      hemolytic disease. Within the past 20 years, however, its incidence in children
      without hemolysis is being diagnosed more frequently. Laparoscopic
      cholecystectomy has become the procedure of choice for gallbladder removal in
      children. Many of the principles for this technique in children are similar to
      those in the adult population. Because of the patient's smaller size and more
      pliable abdominal wall, however, several improvements in technique have been
      developed. In addition, special precautions are necessary in children because of
      other unique characteristics. At Children's Hospital, Vanderbilt University
      Medical Center, 80 infants and children have undergone laparoscopic
      cholecystectomy since June 1990 without intraoperative or postoperative
      complications. Modifications in the operative technique used in these patients
      are detailed.

PMID- 9516554
TI  - Primary laparoscopic endorectal pull-through for Hirschsprung's disease in
      infants and children.
AB  - Colon pull-through for Hirschsprung's disease has classically been performed in
      multiple stages. Open primary pull-through procedures offer the advantages of
      shorter overall hospital stay, decreased morbidity, and earlier intestinal
      continuity, and colostomy is avoided. This article describes the techniques used
      and results obtained in 24 consecutive patients who had a laparoscopic primary
      endorectal pull-through for Hirschsprung's disease. The patients ranged in age
      from a few days to 6 years. Operative times ranged from 1-(1/2) hours to 3-(1/2)
      hours. Perioperative complications were relatively minor. None of the patients
      had clinical enterocolitis after primary laparoscopic pull-through, and there
      were no anastomotic strictures. Average postoperative length of stay was 3-(1/2)
      days. Primary laparoscopic endorectal pull-through is a safe and effective
      alternative to open primary or multistage pull-through procedures.

PMID- 9516555
TI  - Laparoscopic appendectomy in children.
AB  - Laparoscopic appendectomy is a common surgery in most pediatric surgical centers.
      Many studies, mostly retrospective reviews in adults, show the advantages of the
      laparoscopic approach to be less wound infections, shortened postoperative
      recovery, and faster return to normal activities. In addition, less analgesic
      medication is required postoperatively. Potential disadvantages of laparoscopic
      appendectomy include an increased operative time, elevated costs when disposable
      instruments are used, and possibly more infectious complications when performed
      for complicated appendicitis. There are no prospective, randomized trials
      comparing laparoscopic versus open appendectomy in children. Until these studies
      are completed, questions will persist regarding the benefits of laparoscopic
      appendectomy in children.

PMID- 9516556
TI  - Laparoscopic splenectomy in children.
AB  - Splenectomy is frequently performed in children for various hematologic and
      autoimmune diseases. Advanced laparoscopic techniques have now been adapted to
      the pediatric patient making laparoscopic splenectomy an effective and desirable
      technique. This article reviews the indications for splenectomy, the selection
      criteria for the laparoscopic approach, and the technique of laparoscopic
      splenectomy in children. A review of surgical results is included.

PMID- 9516557
TI  - Laparoscopic fundoplication and gastrostomy.
AB  - Fundoplication and gastrostomy are among the more common operative procedures
      performed in infants and children. This article reviews the techniques, results,
      and complications of the surgical treatment of gastroesophageal reflux in 389
      consecutive pediatric patients over the last 5 years. Chronic unremitting
      vomiting, failure to thrive, and an array of pulmonary symptoms were the leading
      indications for fundoplication in these children. Children who eat by mouth were
      primarily treated by a Toupet fundoplication, whereas gastrostomy-fed children
      generally received a Nissen fundoplication. The time to perform fundoplication
      and gastrostomy in our patients averaged about 3 hours for the first 10 patients
      but required a little over 1 hour for the last 50 patients. Most patients were
      discharged by the second or third postoperative day. Recurrent symptoms have
      developed in about 5% of our patients. Five of the 201 children who received a
      Toupet fundoplication (partial wrap) have been converted to a complete wrap
      fundoplication. Two of the patients having a Nissen fundoplication have required
      reoperation for their symptoms. The primary complications were seven cases of
      transient dysphagia, one case of esophageal perforation, and one case of gastric
      perforation. Laparoscopic fundoplication seems to achieve results equivalent to
      open fundoplication and is associated with considerably less postoperative pain
      and morbidity as well as a more rapid recovery.

PMID- 9516558
TI  - Fetoscopy.
AB  - Fetoscopy involves the application of microlaparoscopic technology to fetal
      diagnosis and therapeutic intervention. Though fetoscopy presents many potential
      advantages over open fetal surgery, the primary one is that of decreased
      procedure-induced preterm labor and fetal loss from preterm delivery. The small
      uterine puncture sites required for fetoscopic surgery should, in theory, obviate
      the morbidity of a large hysterotomy. Fetoscopic instrumentation is small by
      design, but this has not limited the breadth of the interventional spectrum,
      because creative applications have been used for the treatment of twin-twin
      transfusion syndrome, twin reversed arterial perfusion sequence, hydronephrosis,
      congenital diaphragmatic hernia, fetal tumors, and myelomeningocele. This article
      examines the fetoscopic experience for these applications, involving over 150
      cases. The results for many procedures are auspicious and will improve as further
      operative experience and newer fetoscopic technologies become available. However,
      as with any novel technology, responsible application must involve careful
      experimentation and an analysis of potential maternal and fetal benefits.

PMID- 9516559
TI  - Laparoscopy for the nonpalpable testis.
AB  - Cryptorchidism represents one of the most common childhood disorders with the
      incidence of testicular maldescent being 0.8% by 1 year of age. Nonpalpable
      testis occurs in approximately 20% of patients with cryptorchidism. Laparoscopy
      for diagnosis and management of nonpalpable testis has shown to be highly
      effective with few complications. This article reviews some of the special
      considerations in performing laparoscopy in children with descriptions about the
      unique features of a child's anatomy and physiology. The role of laparoscopy in
      the evaluation and management of nonpalpable testis is discussed, along with some
      of the controversies about how laparoscopy may be changing our approach to a
      child with a nonpalpable testis.

PMID- 9516560
TI  - Laparoscopic nephrectomy in children.
AB  - Using the techniques for laparoscopic nephrectomy developed in adults, pediatric
      nephrectomy results in equivalent surgical outcomes compared with open surgery.
      To date, both transperitoneal and retroperitoneal laparoscopic approaches to
      nephrectomy for benign renal disease have been described. Controversy exists
      among pediatric urologists, however, regarding the advantages of laparoscopic
      nephrectomy in children because convalescence from an open nephrectomy is also
      rapid. This article reviews the current indications and techniques for
      laparoscopic nephrectomy in children as well as other surgical applications of
      laparoscopy with respect to the pediatric patient.

PMID- 9516561
TI  - Diagnostic laparoscopy for congenital inguinal hernia.
AB  - Repair of indirect inguinal hernias is the most common general surgical procedure
      in infants and children. The question of whether or not to explore the
      contralateral side, however, has been the source of much debate among pediatric
      surgeons. With the advent of laparoscopy and the development of miniature
      telescopes, diagnostic laparoscopy has been advocated to decide in which child
      the contralateral side should be explored and a patent processus vaginalis
      ligated. This article describes the historical perspective in which this
      technique developed, the technique itself, and a report of the author's
      experience.

PMID- 9516562
TI  - Anesthetic considerations for laparoscopy in children.
AB  - As experience, equipment, and techniques have improved, minimally invasive
      surgery is being applied to increasingly younger children. With the advent of
      this new surgical approach, there are also specific modifications necessary in
      anesthetic technique. When considering the anesthetic implications in these
      patients, one must consider both the patient's underlying health status as well
      as physiological derangements induced by the surgery. This article describes the
      specific anesthetic implications for laparoscopic procedures in neonates,
      infants, and children. This information includes the preoperative evaluation,
      intraoperative anesthetic care, and monitoring with a special emphasis on the
      physiological alterations induced by the endoscopic procedures.

PMID- 9516563
TI  - De novo hepatitis B infection after liver transplantation: source of disease,
      incidence, and impact.
AB  - New-onset hepatitis B (de novo B) after liver transplantation (OLTX) is an
      emerging concern. The goals of our study were to determine the incidence and
      pattern of this infection, to attempt determination of risk factors and the role
      of immunosuppression, and to review its morbidity/mortality. Over a 10-year
      period, 1078 OLTX were performed in 956 patients at our institution. Eight
      hundred twenty-six patients had proven negative hepatitis B surface antigen
      (HBsAg) before transplantation. Among these, 14 patients (1.7%), 8 women and 6
      men, ages 21-59 years (median, 42 years), developed positive HBsAg after
      transplantation and were defined as de novo B. In 10 of 14 patients (71%),
      positive HBsAg was revealed during routine annual visits, whereas 4 patients had
      titer verification prompted by illness. Blood product use (cryoprecipitate, fresh
      frozen plasma, platelets, and packed red blood cells) during the transplant
      hospitalization was similar between groups. Pretransplant hepatitis C infection
      was more prevalent among the 14 patients with de-novo B (7 of 14, 50% v 129 of
      812, 16%; P < or = 05). Hepatitis B vaccine had been given to 12 patients (86%)
      (but not given to 2) who developed de novo B. Incidence and severity of rejection
      were similar in both populations, although de novo B patients had more late
      rejections. Our use of immunosuppressive protocols was the same in both groups.
      Mean follow-up of the infected patients is 24 (5-51) months. Twelve of these 14
      de novo B patients were not clinically ill, with normal or near-normal
      transaminase levels. One of 14 has died from complications related to hepatic
      artery revascularization, and another is well after repeat OLTX for biliary
      strictures. Half of these de novo B patients remain free from viral antigens in
      their transplanted liver tissue. The high percentage of positive hepatitis C
      patients who acquire de novo B may indicate a link between these two viral
      infections and potential risk factor for de novo B. The origins of this infection
      are most likely multifactorial, needing further study. De novo B after liver
      transplantation is preliminarily associated with little clinical morbidity and
      mortality.

PMID- 9516564
TI  - Is vaccination against hepatitis B infection indicated in patients waiting for or
      after orthotopic liver transplantation?
AB  - It is a common practice to immunize patients against hepatitis B infection while
      they are waiting for liver transplantation, but the efficacy of this practice is
      unclear. This is a retrospective analysis of the antibody response to 20 microg
      of a recombinant hepatitis B vaccine in patients waiting for and after liver
      transplantation. The response to vaccination was measured 1-3 months after
      completion of the vaccination series. The risk of acquiring hepatitis B virus
      after liver transplant was determined by reviewing the results of tests for
      hepatitis B infection in 171 patients who underwent transplantation for non
      hepatitis B diseases and who had not been vaccinated. Fifty-seven patients
      awaiting transplantation were eligible for the study, and a response to
      vaccination was observed in only 9 (16%). Patients with cholestatic liver disease
      had a significantly higher response (6 of 14; 43%) compared with noncholestatic
      liver disease (3 of 43; 7%; P = .004). Forty-five liver transplant recipients
      were immunized against hepatitis B after transplantation, and only 3 (6.7%)
      developed an antibody response. The frequency of posttransplant hepatitis B
      infection in the 171 patients who were not immunized and who lacked any evidence
      of hepatitis B infection pretransplantation was 4 of 171 (2.3%). The response
      rate to immunization with a recombinant hepatitis B vaccine in patients with
      chronic liver disease who are waiting for a liver transplant and after
      transplantation is poor. Given the poor response to vaccination and the low risk
      of acquiring hepatitis B virus after transplantation, centers need to reconsider
      the routine use of the hepatitis B virus vaccine in patients awaiting liver
      transplantation.

PMID- 9516565
TI  - Vena cava vascular reconstruction during orthotopic liver transplantation: a
      comparative study.
AB  - The aim of this study was to evaluate the influence of preserving the recipient's
      inferior vena cava during orthotopic liver transplantation (OLT) on hemodynamic
      alterations, blood component requirements, postoperative liver and renal
      function, as well as vascular-related complications. A total of 122 OLTs was
      studied. In 35 OLTs, venovenous bypass (BP) was used; in 35 OLTs, bypass was not
      used (NBP); and in 52 OLTs, the recipient's inferior vena cava was preserved
      (PC). Preservation of the inferior vena cava means that venous return is not
      compromised at any time during transplantation. The time of hepatectomy was not
      different among the three groups (208 +/- 11, 188 +/- 13, and 194 +/- 6 minutes
      for BP, NBP, and PC, respectively); however, the total operating time was
      significantly lower in PC patients (492 +/- 24, 459 +/- 18, and 419 +/- 10
      minutes for BP, NBP, and PC, respectively; P = .004, ANOVA). Blood component
      requirements were significantly lower in patients with PC. For red blood cells,
      these were 15.2 +/- 2.6, 16 +/- 3.4, and 7.1 +/- 1.5 units for BP, NBP, and PC,
      respectively (P = .009, ANOVA), and for fresh-frozen plasma, these were 5.4 +/-
      .7, 5.8 +/- .9, and 3 +/- .4 L for BP, NBP, and PC, respectively (P = .005,
      ANOVA). Postoperative liver and renal function did not differ among the three
      groups. The incidence of surgical complications (bleeding and vascular) was
      similar. Preservation of the inferior vena cava of the recipient significantly
      reduces the magnitude of OLT.

PMID- 9516566
TI  - Changes in peripheral blood double-negative T-lymphocyte (CD3+ CD4- CD8-)
      populations associated with acute cellular rejection after liver transplantation.
AB  - Circulating CD3+ T lymphocytes that express neither the CD4 nor CD8 surface
      molecules (double-negative T lymphocytes) are phenotypically and functionally
      distinct from single-positive CD3+CD4+ and CD3+CD8+ lymphocytes and are thought
      to represent a distinct T-cell lineage. The presence of low numbers of double
      negative T cells in healthy individuals and the increase observed in association
      with lymphoproliferative disorders, graft-versus-host disease, and autoimmune
      diseases suggest a pathogenic or immunoregulatory role for this population of T
      lymphocytes. In this study, peripheral blood double-negative T cells were
      assessed quantitatively using three-color flow cytometry in 10 patients after
      liver transplantation during a 6-week period. During this time, 12 episodes of
      histologically proven acute cellular rejection occurred in 8 patients. The median
      postoperative baseline double-negative T-cell count expressed as a proportion of
      the CD3+ T cells was 2.4 +/- 1.2 (median +/- SD; n = 10), which was identical to
      a control group of healthy adults (2.5 +/- 2.4; n = 9). Circulating numbers of
      double-negative T cells were increased significantly during acute cellular
      rejection (6.8 +/- 6.7; P < .001; n = 12). After pulse corticosteroid therapy for
      rejection, there was a significant decrease in the double-negative T-cell
      population (3.5 +/- 5.0 v 6.8 +/- 6.7; P = .01). No significant changes occurred
      in the double-negative T-cell count in the absence of clinical events (2.4 +/-
      3.5; n = 73). These findings are consistent with a role for double-negative T
      cells in the initiation of acute cellular rejection or a possible regulatory role
      in the immunologic changes associated with rejection.

PMID- 9516567
TI  - Occurrence of gammopathies and lymphoproliferative disorders in liver transplant
      recipients randomized to tacrolimus (FK506)- or cyclosporine-based
      immunosuppression.
AB  - Lymphoproliferative disorders (LPDs) are a serious side effect of
      immunosuppression after liver transplantation, and the introduction on the market
      of a new immunosuppressive drug has been associated with an increased risk of
      these disorders. To compare the effect of cyclosporine A (CSA) and FK506 in a
      clinical setting, the incidence of monoclonal or oligoclonal gammopathies known
      to often precede the appearance of LPDs was evaluated. A total of 88 adult
      patients was analyzed, 46 were prospectively randomized to CSA and 42 to FK506
      for immunosuppression. None of these patients had gammopathy before
      transplantation. All the patients were tested for immunoglobulin abnormalities
      five to nine times during a period of 1 year and then two to four times per year
      thereafter from December 1990 until March 1997. The same incidence of serum
      immunoglobulin (Ig) abnormalities was observed in both groups (13%) with a mean
      delay of appearance of 11.1 +/- 5.9 versus 7.6 +/- 3.6 months for CSA and FK506,
      respectively (P > .05). In each group, the gammopathies were transient in 3
      patients and persisted in 2. The class of Ig involved was IgG, and a monoclonal
      component was documented in 2 patients treated with CSA and in 3 patients with
      FK506. One patient treated with FK506 developed an LPD localized to the lymph
      nodes 8 months after the occurrence of serum protein abnormalities. The
      lymphoproliferative lesions subsequently disappeared with the reduction of
      immunosuppression. In this study, an immunosuppressive regimen of FK506 has not
      shown an increased incidence of lymphoproliferation compared with CSA in adult
      liver transplant patients.

PMID- 9516568
TI  - Does N-acetylcysteine improve hemodynamics and graft function in liver
      transplantation?
AB  - The release of toxic oxidative free radicals induced by ischemia and reperfusion
      may jeopardize liver graft function. N-acetylcysteine (NAC) has shown protective
      effects on hypothermic and warm ischemia reperfusion liver injury in animals. NAC
      improves hemodynamics and survival rates in patients with fulminant hepatic
      failure. The aim of this study was to investigate whether intraoperative
      treatment with NAC would improve hemodynamics and postoperative graft function in
      liver transplantation. Sixty patients with chronic end-stage liver disease were
      included in a prospective randomized placebo-controlled study. NAC or the same
      volume of 5% glucose was started during the anhepatic phase. Hemodynamic data and
      calculated tissue oxygenation parameters were compared throughout the procedure.
      Postoperative graft function was assessed by measurements of aminotransferases,
      prothrombin time, and monoethylglycinexylidide test over the 3 first
      postoperative days. Patient demographics were similar before the infusion of NAC
      or glucose. Hemodynamic parameters, oxygen consumption, oxygen delivery, oxygen
      extraction ratio, and lactates were not different throughout the procedure. One
      hour after the revascularization of the hepatic artery, the oxygen extraction
      ratio by the liver was similar (17% +/- 7.6% v 17% +/- 6.2%) in both groups.
      Postoperative graft function was comparable within the 3 first postoperative
      days. This study failed to show any beneficial effect of the intraoperative
      administration of NAC on hemodynamics and graft function in liver transplantation
      in patients with chronic liver disease.

PMID- 9516569
TI  - Brain lactate by magnetic resonance spectroscopy during fulminant hepatic failure
      in the dog.
AB  - A noninvasive test is needed to assess the severity of encephalopathy during
      fulminant hepatic failure. This feasibility study was designed to compare a
      noninvasive test, brain lactate measurement by magnetic resonance spectroscopy,
      with intracranial pressure monitoring in a large animal model of fulminant
      hepatic failure. Five dogs received an intraventricular catheter for intracranial
      pressure measurement. Liver injury was induced by intravenous bolus of D
      galactosamine. Brain lactate concentrations were determined by magnetic resonance
      spectroscopy for up to 48 hours after D-galactosamine administration (t = 0
      hour). A dose of D-galactosamine exceeding 1.5 g/kg resulted in fulminant hepatic
      failure. Brain lactate levels increased to > 10 mmol/L in the two dogs that
      developed severe intracranial hypertension of > 50 mm Hg and sustained cerebral
      perfusion pressures of < 40 mm Hg. Both dogs experienced brain death, 42 and 48
      hours after the administration of D-galactosamine. Brain lactate concentrations
      determined by magnetic resonance spectroscopy were in agreement with brain tissue
      concentrations of lactate determined by high-performance liquid chromatography at
      necropsy. Plasma lactate concentrations were only mildly elevated (3.2 and 4.2
      mmol/L) at the time of brain death. Elevated levels of brain lactate are
      associated with intracranial hypertension and poor neurological outcome during
      fulminant hepatic failure.

PMID- 9516570
TI  - Small bowel bacterial overgrowth as a cause of chronic diarrhea after liver
      transplantation in children.
AB  - Children who have undergone liver transplantation may develop chronic diarrhea
      for a number of reasons. Three children who underwent liver transplantation for
      liver failure, all of whom had had previous biliary and intestinal surgeries and
      whose postoperative course was marked by signs and symptoms of intestinal
      malabsorption including chronic diarrhea, are described. Duodenal aspirates
      showed a panoply of bacterial species, and duodenal histology featured villus
      atrophy in two: one associated with luminal gram-positive cocci and another with
      acute and chronic duodenitis. Oral antibiotics cleared the symptoms. Small bowel
      bacterial overgrowth may need to be considered in children with chronic diarrhea
      after liver transplantation, especially when previous intestinal surgery has
      taken place. Long-term antibiotic therapy may be required to effectively
      eradicate the offending organisms to suppress symptoms.

PMID- 9516571
TI  - Predictors of the cost of liver transplantation.
AB  - BACKGROUND: Orthotopic liver transplantation (OLT) is a highly effective but
      costly therapy for end-stage liver disease. However, there are limited data on
      the demographic and clinical variables that affect cost. We undertook a
      preliminary study using multiple regression techniques to analyze factors that
      influence the cost of OLT. METHODS: Patient and demographic data, including
      laboratory values and charges for all liver transplantations performed between
      June 1992 and June 1993 were analyzed (n = 111). Linear regression with standard
      and log-transformed values was performed by using STATA software (Stata
      Corporation College Station, TX). Independent variables included in the analyses
      were age, sex, United Network for Organ Sharing (UNOS) status, primary versus
      retransplantation, liver-kidney transplantation, and laboratory parameters of
      both liver (aspartate aminotransferase, AST; alkaline phosphatase; bilirubin;
      albumin; and prothrombin time) and kidney (blood urea nitrogen, BUN; creatinine)
      function. An F-to-remove strategy was employed with a significance level set at P
      = .05. RESULTS: The full model with 12 variables explained 37% of the total
      variation in charges. When one excludes variables that did not have a significant
      impact on cost, the remaining significant variables were BUN and UNOS status 1.
      The final model was Charges (US$) = 3,407 x BUN + 74,474 x status 1 + 102,662.
      This model accounted for 29% of the total variability with BUN accounting for the
      vast majority (26%). CONCLUSIONS: Renal function is the most important predictor
      of cost of OLT (P < .001). UNOS status 1 further increases cost, but other
      hospitalized patients have similar costs when one controls for other clinical
      variables. The degree of liver impairment is less important in predicting cost.

PMID- 9516572
TI  - Severe pulmonary hypertension and amelioration of hepatopulmonary syndrome after
      liver transplantation.
AB  - A patient with end-stage liver disease as a result of alpha1-antitripsin
      deficiency presented for orthotopic liver transplantation. The liver cirrhosis
      was complicated by portal hypertension and hepatopulmonary syndrome resulting in
      varicosities and severe hypoxia (room air oxygen saturation 69%). After
      transplantation, the hepatopulmonary syndrome improved but, over the next 14
      months, the patient developed severe pulmonary hypertension. Six years
      posttransplantation, his room air oxygen saturation was 95% with pulmonary artery
      pressures of 109 mm Hg systolic and 26 mm Hg diastolic (mean 55 mm Hg) and a
      pulmonary vascular resistance 688 dynes x sec x cm.

PMID- 9516573
TI  - Progress in transgenic pigs for xenotransplantation.

PMID- 9516574
TI  - Editorial response: De novo HBV infections after liver transplantation.

PMID- 9516576
TI  - Call for Nominations Liver Transplantation and Surgery Editorship
AB  - No Abstract Copyright

PMID- 9516575
TI  - Vaccination of patients with liver disease: who, when, and how.

PMID- 9516577
TI  - Sphincter preservation in rectal cancer. Introduction.

PMID- 9516578
TI  - Sphincter preservation in rectal cancer. External-beam radiation therapy alone.
AB  - Surgery with or without adjuvant radiation therapy and chemotherapy is the
      standard treatment for patients with resectable rectal carcinoma. Many patients,
      however, are medically unfit or simply refuse surgery that could result in a
      colostomy. This article reviews the results of external-beam radiation therapy
      alone for selected patients with rectal carcinoma and its role in preserving
      anorectal function. For patients with mobile tumors, a 5-year survival and local
      relapse-free rate of 30% and 25%, respectively, can be expected after external
      beam radiation therapy alone, and 60% remain colostomy free. Results of radiation
      therapy alone in patients with fixed or unresectable tumors are poor. Although
      more than a third of patients remain colostomy-free, only 5% of patients survive
      5 years. In patients with mobile rectal carcinomas that are not amenable to
      sphincter-preserving surgery, who are unfit medically for radical surgery, or who
      refuse a colostomy, external-beam radiation therapy offers the reality of
      sphincter preservation and the possibility of long-term tumor control.

PMID- 9516579
TI  - Sphincter preservation in rectal cancer. Endocavitary radiation therapy.
AB  - Endocavitary radiation therapy (Endo RT) is performed mainly with a contact x-ray
      tube. Interstitial brachytherapy is a supplementary method to boost the tumor
      bed. Only strictly selected patients can be treated for cure by Endo RT. More
      than 1,000 patients have been treated in Europe and North America since 1950. In
      T1 N0 adenocarcinoma, the primary local control rate is close to 90%. The overall
      5-year survival is between 60% and 90% depending on patient selection. Careful
      follow-up is necessary because the majority of local failures can be salvaged,
      usually by radical surgery. The main advantages of Endo RT are a fully ambulatory
      and simple treatment that can be applied even in frail or elderly inoperable
      patients, a low risk of complications, and an inexpensive treatment. Results show
      it is possible to perform curative treatment in patients with more advanced
      rectal carcinoma. With the combination of external-beam radiation therapy and
      Endo RT in stage T2-3 N0-1 tumors, the primary local control rate is around 70%,
      and the incidence of severe radiation toxicity is less than 5%. Overall 5-year
      survival is between 50% and 70%. Endo RT can also be used as an adjuvant
      treatment after local excision, in the treatment of villous adenomas, and for
      palliation of advanced inoperable tumors.

PMID- 9516580
TI  - Sphincter preservation in rectal cancer. Local excision followed by postoperative
      radiation therapy.
AB  - The management of distal rectal cancer is in evolution. Although abdominoperineal
      resection has been long regarded as the definitive treatment of distal rectal
      cancer, it is associated with significant morbidity--loss of anorectal function
      with a permanent colostomy and a high incidence of sexual and genitourinary
      dysfunction. To overcome these limitations, innovative efforts are underway
      studying the feasibility and efficacy of a variety of sphincter-preserving
      operations, usually in combination with radiation therapy and chemotherapy. Local
      excision procedures with adjuvant therapy represent one such treatment strategy
      that attempts to optimize local control and survival with preservation of
      sphincter integrity. This article summarizes the current role of local excision
      and postoperative irradiation and chemotherapy for patients with carcinoma of the
      rectum.

PMID- 9516582
TI  - Sphincter preservation in rectal cancer. Preoperative radiation therapy followed
      by local excision.
AB  - Radiation therapy followed by local excision results in local control rates that
      appear comparable to those of local excision alone (in highly selected patients)
      or local excision followed by adjuvant radiation therapy. A significant drawback
      of this approach, however, is the potential loss of important histological
      information, such as risk of lymph node metastasis, depth of tumor penetration,
      and presence of lymphatic or vascular invasion. Radiation therapy followed by
      local excision may be an option for treatment of more advanced T3 rectal cancers
      in patients who either refuse radical surgery or are medically unfit. The
      available data in the literature do not support the routine use of local excision
      after radiation therapy in otherwise healthy patients with locally advanced
      rectal cancer.

PMID- 9516581
TI  - Sphincter preservation in rectal cancer. Preoperative radiation therapy followed
      by low anterior resection with coloanal anastomosis.
AB  - The advantage of preoperative therapy in patients with clinically resectable
      transmural rectal cancer is to increase sphincter preservation while obtaining a
      high likelihood of local control. In patients who undergo a prospective clinical
      assessment and are declared to require an abdominoperineal resection,
      preoperative radiation therapy, either alone or when combined with chemotherapy,
      allows approximately 80% of patients to undergo a low anterior resection with or
      without colo anal anastomosis. The majority have good-to-excellent sphincter
      function. This conservative approach may be an alternative to an abdominoperineal
      resection in selected patients.

PMID- 9516583
TI  - Sphincter preservation in rectal cancer. Surgical considerations for local
      excision.
AB  - The principles involved in selecting patients for local excision of rectal
      cancers, as well as the various techniques and principles for local resection,
      are detailed in this article. The assessment of the current role of this
      technique awaits further maturation of data from phase II clinical trials. The
      addition of chemotherapy and radiation therapy may allow treatment of more
      advanced rectal cancers by these techniques.

PMID- 9516584
TI  - Sphincter preservation in rectal cancer. Technical considerations for coloanal
      anastomosis and J-pouch.
AB  - Most patients with midrectal cancer undergo a sphincter-preserving operation
      using modern bowel stapling techniques. In patients with bulky tumors or
      unfavorable pelvic anatomy, however, abdominoperineal resection with permanent
      colostomy may be performed for technical reasons, not based on oncologic
      clearance needs. In addition, low-lying tumors treated initially with
      preoperative chemoradiation are often downstaged, increasing the opportunity for
      restorative procedures. Treatment by total proctectomy and peranal sutured
      coloanal reconstruction fulfills the need for adequate oncologic clearance and
      satisfactory bowel function. Sharp pelvic dissection with removal of the entire
      rectal mesentery, adequate mobilization of the left colon, and precise
      anastomotic technique are required for optimal results. Creation of a colon J
      pouch increases the capacity of the reconstructed rectum and greatly reduces the
      time required for functional adaptation in the postoperative period. Although
      irregular evacuation and other minor problems can persist, permanent colostomy is
      avoided, and patient satisfaction is high. For cancers of the middle and distal
      rectum, total proctectomy with coloanal reconstruction is an important treatment
      option that can improve quality of life without compromising cancer treatment.

PMID- 9516586
TI  - Introduction 
AB  - No Abstract Copyright

PMID- 9516585
TI  - Clinical and molecular prognostic factors in sphincter-preserving surgery for
      rectal cancer.
AB  - As many as a third of patients with rectal cancers may be candidates for
      sphincter preservation surgery. The goal of the conservative management of
      adenocarcinoma of the distal rectum is to preserve rectal sphincter function
      without sacrificing local tumor control. To achieve this goal, a combined
      modality approach is necessary because multimodality therapy for more advanced
      disease has improved both local control and survival. Candidates for local
      excision are those with adenocarcinomas with a maximal diameter of less than 4
      cm, mobile, and not poorly differentiated or mucinous and within 10 cm of the
      anal verge--usually within 6 cm. These criteria should be defined objectively by
      biopsy combined with state-of-the-art endorectal imaging. Newer molecular markers
      that are associated with prognosis and response to therapy may also be important
      for assessing prognosis, probability of local recurrence, and whether
      conservative treatment is appropriate. Patients with T0-3 N0 lesions meeting
      these standard clinicopathologic criteria have been treated successfully with
      wide local excision combined with chemotherapy and radiotherapy. Patients with
      larger or more advanced lesions may undergo low anterior resection with coloanal
      anastomosis. After resection, radiotherapy to at least 45 to 50 Gy is delivered
      to the pelvis and tumor bed often with concomitant chemotherapy. The overall rate
      of local failure in prospective single-institution trials in which local excision
      is performed with postoperative chemoradiotherapy has been 5% for T1 lesions, 7%
      for T2 lesions and 24% for T3 lesions. Although single-institution studies have
      supported the concept of conservative therapy, the safety and efficacy of this
      approach must still be confirmed in a multicenter, prospective trial, such as
      that underway in several of the cooperative oncology groups, before it may be
      considered a standard of practice.

PMID- 9516587
TI  - PSA for outcome prediction and posttreatment evaluation following radiation for
      prostate cancer: do we know how to use it?
AB  - Pretreatment prostate-specific antigen (PSA) has been shown to be a powerful
      predictor of expected outcome after radiation for prostate cancer. Additional
      measures such as recursive partitioning analysis and PSA Cancer Volume
      calculations are further refining this useful tool to provide the greatest degree
      of prognostic information. The post-treatment PSA level is also being used as a
      means to assess therapeutic efficacy rapidly and objectively. Although no single
      PSA value has been shown to equate to long-term clinical tumor control
      consistently, consensus has been reached regarding the value of a rising PSA
      level as an early surrogate for tumor recurrence. Since the first introduction of
      PSA as a tumor marker, we have become much more comfortable with what it means,
      the ways it can help us, and how to use it.

PMID- 9516588
TI  - Radiation therapy or prostatectomy: an old conflict revisited in the PSA era. A
      radiation oncologist's viewpoint.
AB  - A close examination of the outcomes for the radical treatment of prostate cancer
      in the prostate-specific antigen (PSA) era shows no clear advantage to radical
      prostatectomy over external-beam radiation. Both modalities are highly effective
      against small impalpable tumors of low Gleason grade and with PSA values less
      than 10 ng/mL. Both modalities struggle against all other stages of prostate
      cancer. Radiation and surgery are currently in states of rapid evolution, and the
      results emerging become quickly outdated. It is hoped that the newer, more
      aggressive approaches will help a significant number of patients, perhaps the
      majority, not currently being cured by radical therapy.

PMID- 9516589
TI  - Radiation therapy versus radical prostatectomy in the PSA era: a urologist's
      view.
AB  - In the absence of a randomized trial directly comparing outcomes in men with
      localized prostate cancer treated by radical prostatectomy with treatment by
      radiation therapy, only an approximate answer regarding the relative efficacies
      of these modalities can be achieved. However, retrospective studies which
      examined outcomes based on pretreatment parameters intrinsic to the tumors have
      demonstrated that when stratified by grade and prostate specific antigen (PSA),
      the rates of cancer control for these therapies are similar at 5 years
      posttreatment. These modalities differ in other important ways, including acute
      toxicity, patient satisfaction, posttreatment quality of life, and ease of
      salvage of treatment failures. A consideration of all of these factors is
      necessary to arrive at the appropriate choice of therapy for each patient.

PMID- 9516590
TI  - Androgen ablation in addition to radiation therapy for prostate cancer: is there
      true benefit?
AB  - Prostate cancer patients may now be identified as having a high risk of failing
      single-modality treatment based on pretreatment prostate specific antigen (PSA),
      Gleason score, and palpable stage. In particular, a PSA greater than 20 ng/mL
      portends a biochemical failure rate of 50% to 80% when radiation therapy,
      surgery, or androgen ablation is administered individually. A number of
      randomized trials as well as retrospective data show that failure rates are
      significantly reduced by combining androgen ablation and radiation. The improved
      results, however, are complicated by the ability to salvage radiation alone
      treated patients with androgen ablation and the possibility of less effective
      salvage (or no effective salvage in the case of permanent androgen ablation) for
      patients treated with androgen ablation plus radiation. Thus, survival, which is
      obscured by high rates of intercurrent deaths in this elderly population, is the
      most important end point in such studies. Two randomized trials, one from the
      Radiation Therapy Oncology Group (RTOG) and one from the European Organization
      for Research on Treatment for Cancer (EORTC), of radiation therapy plus adjuvant
      (as opposed to neoadjuvant) androgen ablation have reported survival gains over
      radiation therapy alone. In contrast, one neoadjuvant trial from the RTOG failed
      to show a survival benefit when androgen ablation was added to radiation therapy.
      In this study, however, androgen ablation was administered for only 4 to 5
      months, which may be insufficient. The weight of the evidence to date indicates a
      true benefit with androgen ablation plus radiation therapy over radiation therapy
      alone. There are clearly many unanswered questions concerning the optimal timing
      of androgen ablation and radiation therapy (neoadjuvant versus adjuvant), length
      of time that androgen ablation should be administered (6 months versus 3 years
      versus permanent), type of androgen ablation (total androgen ablation or not),
      and appropriate patient population (definition of high risk). The planned future
      clinical trials will address many of these issues; however, the full potential of
      this approach requires an understanding of the fundamental mechanisms involved.

PMID- 9516591
TI  - Three-dimensional conformal radiotherapy and dose escalation: where do we stand?
AB  - Three-dimensional conformal radiotherapy is an effective means of delivering high
      doses of radiation with enhanced precision. Several institutions have gained
      substantial experience using this modality for patients with clinically localized
      prostate cancer. Reports from these centers have demonstrated not only excellent
      tolerance despite the administration of higher radiation doses, but improved
      biochemical and local control outcomes as well. Meticulous attention to treatment
      technique and dose volume histogram analysis are critical for the safe
      implementation of these higher doses. The emergence of intensity-modulated
      treatment planning has provided the opportunity at our institution to further
      escalate the radiation dose to 86.4 Gy while still respecting the surrounding
      normal tissue tolerance. Phase I studies will need to continue to define more
      clearly the maximal dose of radiation that can be delivered safely with this
      modality. Current studies indicate a direct correlation between dose and prostate
      specific antigen (PSA) relapse-free survival response for patients with
      intermediate and high-risk prognostic features. These patients likely represent
      the ideal cohort for future studies designed to investigate the impact of dose on
      biochemical and disease-free survival outcome.

PMID- 9516592
TI  - Particle beam radiation therapy in prostate cancer: is there an advantage?
AB  - Hadron therapy uses heavy particles to deliver therapeutic ionizing energy. Each
      particle's inherent attributes determine the pattern of energy deposited by its
      beam, expressed in macro (conformability to a three-dimensional target volume)
      and micro (radiobiologic properties) distributions. Mass and charge regulate the
      inherent properties; beam energy provides a controllable, variable
      characteristic. Generally, heavy charged particles provide superior
      macrodosimetric properties; heavy particles (charged or not) have microdosimetric
      characteristics that produce high linear energy transfer (LET). Neutron
      macrodosimetry is similar to that of photons. Protons and helium ions possess
      superior macrodosimetric properties, plus microdosimetric characteristics
      resulting in low LET, yielding beam characteristics that approach the ideal for
      clinical radiotherapy. Hadron therapy for prostate cancer has been limited by the
      availability of appropriate treatment facilities. Nonetheless, encouraging
      results have been obtained. Neutron therapy demonstrated improved overall
      survival in a multi-institutional randomized trial, and improved local disease
      control in a subsequent trial. Proton radiation forms the boost component of
      several conformal dose-escalation studies. A Loma Linda University study
      demonstrated low treatment-related morbidity despite a prostate dose of 75 CGE;
      late-morbidity data were superior to published reports from multi-field,
      conformal photon therapy. A Phase III dose-escalation study of protons for early
      prostate cancer is proceeding.

PMID- 9516593
TI  - Radioisotopic implantation for carcinoma of the prostate: does it work better
      than it used to?
AB  - Transperineal interstitial permanent prostate brachytherapy is being selected as
      the treatment of choice for early-stage prostatic carcinoma with increasing
      frequency by both patients and medical practitioners. This trend is surprising to
      many who are aware of the disappointing results following the retropubic
      technique of a few decades ago. Others advocate that the newer techniques, which
      use technologically advanced imaging of the prostate and sophisticated treatment
      planning systems, allow highly conformal source placement within the gland,
      resulting in a dose distribution that is superior to that previously achieved.
      Does improved dose distribution correlate with a higher local control rates in
      prostate implant patients? This review compares the historical technique of open
      laparotomy and retropubic implantation as practiced at Memorial Sloan-Kettering
      Cancer Center in the 1970s to the contemporary technique of transperineal
      ultrasound-guided permanent seed placement of the 1990s. The results to date show
      that the present techniques are producing substantially better outcomes, probably
      resulting from better patient selection as well as improved dose delivery. This
      is a US government work. There are no restrictions on its use.

PMID- 9516594
TI  - Radiation therapy after prostatectomy: now or later?
AB  - Patients with pathological stage T3 or T4 prostate cancers who have undetectable
      prostate-specific antigen (PSA) levels after radical retropubic prostatectomy
      (RRP) have a substantial risk of recurrence. The first sign of recurrence is a
      rising PSA level, which precedes clinical evidence of failure by months to years.
      Adjuvant radiation therapy can significantly reduce the risk of failure in these
      patients. Patients with rising PSA levels after RRP can be salvaged with
      radiation therapy. Larger series report that between 30% and 54% of carefully
      staged patients can be salvaged with radiation therapy alone. It is possible that
      more patients may be salvaged in the future with the use of combined radiation
      therapy and hormonal therapy. Although one cannot be certain which approach
      adjuvant or salvage radiation therapy- is better, studies are being performed
      that will help clarify this clinical dilemma.

PMID- 9516595
TI  - Paclitaxel in Breast Cancer: Putting the Evidence into Practice. Proceedings from
      the Pan European Interactive Forum. Lisbon, Portugal, June 28, 1997.

PMID- 9516596
TI  - Paclitaxel plus doxorubicin in metastatic breast Ca: the Milan experience.
AB  - A pilot study conducted at the National Cancer Institute in Milan, Italy assessed
      the efficacy of six or eight cycles of paclitaxel (Taxol) 200 mg/m2 q3wks plus
      doxorubicin (Adriamycin) (60 mg/m2q3wks) in 49 women with metastatic breast
      cancer who had received no prior chemotherapy. This study suggested that
      paclitaxel and doxorubicin should be considered for previously untreated patients
      who have been initially diagnosed with metastatic breast cancer and have a good
      performance status. The probability of complete response in these patients can be
      enhanced by continuing treatment with single-agent paclitaxel, and the risk of
      cardiotoxicity can be minimized by keeping the cumulative dose of doxorubicin
      below 360 mg/m2. Based on the experience in Milan, this combination is one of the
      most effective regimens for the treatment of women with breast cancer. Indeed,
      the convenience, efficacy, and tolerability of the combination justify the large
      trials that are currently evaluating its effects in women with operable breast
      cancer.

PMID- 9516597
TI  - Dose-dense paclitaxel-containing adjuvant therapy for breast cancer.
AB  - The use of dose-dense therapy is one approach to overcoming the "resistance" of
      malignant cells to adjuvant therapy caused by inadequate drug exposure. In this
      approach, active drugs are delivered sequentially at their "ideal" dose level
      separated by short intertreatment intervals. Thus, dose intensification is
      achieved by means of rapidly recycled treatments rather than by dramatic dose
      escalation. To overcome absolute cellular resistance, the addition of new,
      active, non-cross-resistant drugs holds great promise and has specifically
      motivated the testing of the taxanes. This article describes the results of
      clinical trials of dose-dense therapy, with particular emphasis on attempts to
      incorporate one taxane, paclitaxel (Taxol), into the dose-dense regimen of
      sequential doxorubicin and cyclophosphamide--the so called A-->T-->C regimen, and
      into more conventional regimens.

PMID- 9516598
TI  - One-hour paclitaxel via weekly infusion: dose-density with enhanced therapeutic
      index.
AB  - A preliminary report of phase II trial of paclitaxel (Taxol) administered in a
      dose-dense manner as first- and second-line therapy for metastatic breast cancer
      is presented. Patients who had received one or two prior chemotherapy regimens
      for metastatic disease or in the adjuvant setting were eligible. Prior treatment
      with an anthracycline was permitted, but patients who had previously received
      taxanes were excluded. Initial dose was paclitaxel 100 mg/m2 infused over 1 hour
      weekly until disease progression or intolerable toxicity. To date, significant
      activity and a highly favorable toxicity profile have been observed with 1-hour
      paclitaxel < or = 100 mg/m2. Less myelosuppression occurred than would have been
      expected with a standard regimen (paclitaxel 175 mg/m2 given over 3 hours q3wks).
      Neurotoxicity became dose limiting at paclitaxel > 100 mg/m2/wk. The apparent
      safety and high therapeutic index of paclitaxel administered in a dose-dense
      fashion increases therapeutic options for patients with breast cancer, and
      further studies are warranted.

PMID- 9516599
TI  - Taxanes in adjuvant and neoadjuvant therapies for breast cancer.
AB  - Paclitaxel (Taxol) is a diterpene originally obtained from the bark of the
      Pacific Yew Tree, Taxus Brevifolia. Its mechanism of action is unique. It
      stabilizes microtubule polymerization, thus blocking cells in the G2/M phase of
      the cell cycle. In breast cancer, initial studies using paclitaxel demonstrated
      high activity. The first study was reported in 1991 by Holmes et al who gave
      paclitaxel as a 24-hour infusion at 250 mg/m2 to 25 patients with metastatic
      breast cancer following only one prior chemotherapy regimen--they achieved a 56%
      response rate. Since then, numerous studies have confirmed the effectiveness of
      paclitaxel in patients with metastatic disease. A second taxane, docetaxel
      (Taxotere), has also demonstrated excellent activity. Clinical research is now
      focused on integrating the taxanes into combination drug regimens and into
      neoadjuvant and adjuvant schedules for patients with early stage breast cancer,
      as well as looking at the biologic determinants of response and resistance to
      taxanes. This article will review developments in the use of taxanes in the
      adjuvant and neoadjuvant settings and it will review the information on possible
      molecular markers that may be useful in predicting tumor responsiveness to
      taxanes.

PMID- 9516600
TI  - Paclitaxel plus vinorelbine in metastatic breast Ca patients with
      contraindications to receive anthracyclines.
AB  - Thirty-three metastatic breast cancer patients with prior chemotherapy (adjuvant
      alone, 9 patients; chemotherapy for metastatic disease alone, 13 patients;
      chemotherapy for both, 11 patients) received paclitaxel (Taxol) 135 mg/m2 over 1
      h followed by vinorelbine (Navelbine) 30 mg/m2 over 10 minutes on day 1 every 3
      weeks. All patients had contraindications to receive anthracycline therapy
      (primary resistance, 10 patients; dose reaching the maximum recommended dose
      and/or myocardiopathy, 23 patients). Twenty-eight patients had previously
      received anthracyclines, and the remaining 5 had received prior CMF
      (cyclophosphamide, methotrexate, fluorouracil). The combination of paclitaxel
      plus vinorelbine was given as first-line chemotherapy for metastatic disease to 9
      patients and as second- or third-line to the remaining 24 patients. The mean
      number of metastatic sites was 2 (range 1-5). Twenty-two patients had visceral
      involvement. Overall, 3 complete and 13 partial responses were observed among the
      33 patients (objective response rate 48.5%, 95% confidence interval 31% to
      66.5%). The response rate in patients receiving the regimen as first-line
      chemotherapy was 67% (6/9 patients), compared to 42% (10/24) in those receiving
      the regimen as second- or third-line chemotherapy. Primary anthracycline
      resistant patients showed a response rate of 60% (6/10), whereas the remaining
      patients had a response rate of 43.5% (10/23). The main toxicities were grade 3
      alopecia (92%), grade 3-4 neutropenia (28%), neutropenic fever (16%), grade 1-2
      peripheral neuropathy (44%), arthralgias-myalgias (32%), and hypersensitivity
      reactions (8%). Phlebitis was a significant clinical problem in patients
      receiving the drugs through a peripheral vein.

PMID- 9516602
TI  - Metastatic breast cancer: experience with the combination paclitaxel plus
      epirubicin.
AB  - This study evaluated the safety and feasibility of the combination of paclitaxel
      (Taxol) and epirubicin, the 4'-epimer of doxorubicin, in women with metastatic
      breast cancer. A total of 85 patients with histologically proven metastatic
      breast cancer were treated in two cohorts; epirubicin 60 mg/m2 i.v. infused over
      1 hour, followed by paclitaxel 175 mg/m2 i.v. infused over 3 hours (group A), and
      epirubicin 90 mg/m2 i.v. via a 1-hour infusion, followed by paclitaxel 175 mg/m2
      i.v. via a 3-hour infusion (group B). Of the 85 patients, 68 were evaluable for
      response and toxicity (43 in group A and 25 in group B). The combination was
      generally well tolerated. The higher epirubicin dose induced more severe
      neutropenia and one case of cardiotoxicity. Nonhematologic toxicities were mild,
      with no severe mucositis or peripheral neuropathy reported. Overall, 68% of
      patients in group A and 68% of patients in group B responded. A phase III trial
      comparing paclitaxel, 175 mg/m2, plus epirubicin, 60 mg/m2, with the standard
      combination of epirubicin, 60 mg/m2, and cyclophosphamide (Cytoxan, Neosar), 600
      mg/m2, is currently in progress.

PMID- 9516601
TI  - Fluorouracil-based combinations in the treatment of metastatic breast cancer.
AB  - Although combination chemotherapy regimens may prolong survival for selected
      patients with metastatic breast cancer, few, if any, are cured. The standard
      regimens used in treatment, e.g., CMF (cyclophosphamide, methotrexate, and
      fluorouracil [5-FU]), FAC (5-FU, Adriamycin, and cyclophosphamide), and FEC (5
      FU, epirubicin, and cyclophosphamide), were developed over a decade ago. Current
      efforts to improve therapeutic efficacy have concentrated on decreasing drug
      toxicity and increasing drug doses (e.g., high-dose chemotherapy with peripheral
      stem-cell support). An important alternative approach to increasing therapeutic
      efficacy focuses on altering the administration schedules of well-known
      chemotherapeutic agents and introducing active new agents. One of the most
      frequently used cytotoxic drugs, fluorouracil (5-FU), has documented activity in
      a variety of malignancies, most notably, breast cancer and gastrointestinal tract
      cancers. However, despite broad clinical experience with 5-FU, our knowledge
      about the mechanisms of resistance to the various administration schedules used
      is limited. In vitro data and clinical experience show that resistance to one
      schedule of 5-FU can be overcome by using alternative schedules, in particular, a
      protracted infusion. This article discusses our clinical experience with weekly
      high-dose 24-hour infusions of 5-FU in combination with folinic acid (leucovorin)
      alone and together with paclitaxel (Taxol) for the treatment of advanced breast
      cancer.

PMID- 9516603
TI  - Paclitaxel plus epirubicin in advanced breast cancer.
AB  - This phase I-II study aimed to determine the maximum tolerated dose (MTD) of
      paclitaxel (Taxol), infused over 3 hours, when combined with a fixed dose (90
      mg/m2) of epirubicin. Other aims were to investigate the combination's plasma
      pharmacokinetics, toxicity, and activity in 50 patients with previously untreated
      metastatic breast cancer, as well as its ability to mobilize peripheral blood
      stem cells (PBSCs). The initial dose of paclitaxel, 135 mg/m2, was increased by
      20 mg/m2 in subsequent cohorts of six patients until dose-limiting toxicity (DLT)
      occurred. The DLT of the combination was febrile neutropenia in two of eight
      patients who received paclitaxel at 225 mg/m2. The concentration of epirubicinol,
      the major metabolite of epirubicin, decreased from 47.3 +/- 9.4 ng/mL at 175
      mg/m2 of paclitaxel to 37.9 +/- 7.5 ng/mL at the 225-mg/m2 dose. The most
      relevant toxicity was grade 4 neutropenia (61% of all the courses). Cardiac
      toxicity included three patients (6%) developing congestive heart failure
      responsive to therapy. Among 49 evaluable patients, 41 responses (84%) were
      observed (95% confidence interval [CI], 70% to 92%) and 9 (19%) of these were
      complete. In 21 patients, we evaluated the mobilization of PBSCs after this
      regimen plus a colony-stimulating factor. The median number of CD34+ cells was
      61.7/microL (range, 6.8 to 201/microL), and a median of 6.3 x 10(6)/kg of CD34+
      cells have been harvested with a single leukapheresis.

PMID- 9516604
TI  - Paclitaxel and carboplatin as first-line chemotherapy for advanced breast cancer.
AB  - In a phase II study, 66 patients with advanced breast cancer (median age 56
      years; range, 28 to 75 years) were treated with paclitaxel (Taxol), 175 mg/m2
      infused over 3 hours, and carboplatin (Paraplatin), dosed to attain an area under
      the concentration-time curve (AUC) of 6 mg x min/mL; treatment was repeated every
      3 weeks. A total of 38 (58%) patients had received prior adjuvant chemotherapy,
      21 with a regimen containing an anthracycline or mitoxantrone (Novantrone). As of
      May 1997, 295 cycles of paclitaxel-carboplatin have been administered, 248 (84%)
      at full dose. The relative dose intensity of paclitaxel is 0.9 (range, 0.5 to
      1.2). Of the 66 patients, 8 (12%) have achieved a complete response and 27 (41%)
      a partial response, for a total response rate of 53%. Grade 3 to 4 toxicities
      have included anemia (5%), leukopenia (25%), thrombocytopenia (5%),
      nausea/vomiting (7%), myalgias/arthralgias (4%), allergic reaction,
      neurotoxicity, and infection (2% each). Alopecia has been universal. Median time
      to progression is 8.9 months; median survival has not yet been reached. We
      conclude that the combination of paclitaxel and carboplatin has significant
      activity in advanced breast cancer and can easily be administered on an
      outpatient basis with manageable toxicity.

PMID- 9516605
TI  - Autocrine growth factors and neuroendocrine markers in the development of small
      cell lung cancer.
AB  - Two different clinical trials using biological agents directed against an
      autocrine growth factor and a surface marker of neuroendocrine differentiation
      have been used for patients with relapsed small-cell lung cancer. In a phase II
      trial, an antibody (2A11) directed against the autocrine growth factor gastrin
      releasing peptide has been used to treat patients with relapsed small-cell lung
      cancer. One of 12 evaluable patients treated with 2A11 250 mg/m2 three times
      weekly for 4 weeks achieved a complete response. An antibody directed against the
      neural cell adhesion molecule has been linked to a modified ricin molecule. This
      immunotoxin, N901-bR, has undergone phase I testing, and a recommended phase II
      dose of 30 micrograms/kg/day for 7 days by continuous infusion has been
      determined. In the phase I trial, one of 21 patients with relapsed or refractory
      small-cell lung cancer had a partial response to this treatment. Therefore, it
      appears that an antibody directed against an autocrine growth factor and an
      immunotoxin directed against a surface marker of neuroendocrine differentiation
      can inhibit the growth of small-cell lung cancer in vitro and in vivo; both
      produced some evidence of antitumor activity in patients. Further studies with
      agents directed against autocrine growth factors and surface markers of
      neuroendocrine differentiation appear warranted.

PMID- 9516606
TI  - Integrating thoracic radiotherapy in the treatment of limited small-cell lung
      cancer.
AB  - Although the need to combine thoracic radiotherapy with systemic chemotherapy in
      the curative treatment of limited small-cell lung cancer is now widely
      acknowledged, there is substantial disagreement on how best to do this. This
      paper reviews radiotherapeutic factors but also highlights the important
      interactions that occur with some classes of chemotherapeutics. Studies examining
      variables like dose and volume are clearly in order. Concurrent therapy given
      early has been adopted throughout most of the world, except Europe. The reasons
      for this are explored. Multiple studies are now showing excellent results with
      fewer total cycles of chemotherapy. Integration of newer drugs is another
      challenge for clinical investigators at the close of this century.

PMID- 9516607
TI  - Prophylactic cranial irradiation in small-cell lung cancer: is it ever indicated?
AB  - Prophylactic cranial irradiation (PCI) is being reintroduced into multimodality
      treatment protocols of patients with small-cell lung cancer (SCLC). The history
      of its use brings interesting insights into clinical evaluations of treatment
      strategies and design of relevant and informative trials. The critical issues of
      effectiveness and overall health gains of prophylactic cranial irradiation have
      been addressed in a series of recently completed clinical trials. These trials
      tested prophylactic cranial irradiation in small-cell lung cancer patients
      achieving good response to induction therapy and confirmed the ability of
      standard prophylactic cranial irradiation schedules to significantly reduce the
      lifetime risk of brain metastases. A subset of these trials evaluated
      neurotoxicity in a formal and prospective manner. No sustained or significant
      detriment in neuropsychometric function could be linked to the use of
      prophylactic cranial irradiation. In addition, all the large trials have shown a
      consistent survival advantage in favor of the prophylactic cranial irradiation
      arm. None of the individual sample sizes were large enough to statistically
      confirm this survival benefit, but a meta-analysis is in progress and will report
      on this aspect of evidence shortly. Issues that remain to be answered are the
      optimal dose and schedule of prophylactic cranial irradiation as well as the
      timing of this administration. These questions form the nucleus of the next
      generation of collaborative trials that are being designed.

PMID- 9516608
TI  - Small-cell lung cancer: is there a standard therapy?
AB  - For more than 25 years, chemotherapy has been the cornerstone of treatment for
      small-cell lung cancer. Many studies have tested a wide variety of drugs in
      different combinations, resulting in a number of standard combination
      chemotherapy options. Radiotherapy to the primary tumor, after having been out of
      favor for a time, is now considered an element of standard therapy for patients
      with limited disease, although a number of questions remain concerning its
      optimal use. Because the overall outcome of therapy for small-cell lung cancer is
      not at all satisfying, further research is needed to find a better use of old and
      new drugs. This article provides a historic overview of therapy for small-cell
      lung cancer, followed by examples of emerging concepts and current research in
      such areas as dose escalation, second-line therapy, and new drugs. Selection of
      optimal first-line therapy for the individual patients is also discussed, based
      on disease stage, performance status, and other considerations.

PMID- 9516609
TI  - Paclitaxel, carboplatin, and extended-schedule oral etoposide for small-cell lung
      cancer.
AB  - We evaluated the feasibility and efficacy of combination paclitaxel (Taxol) (via
      1-hour infusion), carboplatin (Paraplatin), and oral etoposide (VePesid) in the
      first-line treatment of patients with small-cell lung cancer. Between June 1993
      and July 1996, 117 patients with small-cell lung cancer. were treated in two
      sequential phase II studies. The first 38 patients received a lower-dose regimen:
      paclitaxel 135 mg/m2, via 1-hour infusion; carboplatin dosed to an area under the
      concentration-time curve (AUC) of 5.0, and oral etoposide 50 mg alternating with
      100 mg on days 1 through 10. Based on a very favorable toxicity profile, the
      paclitaxel and carboplatin doses were increased in the subsequent cohort of 79
      patients (paclitaxel 200 mg/m2 by 1-hour infusion; carboplatin target AUC
      increased to 6.0). Thoracic radiation therapy (1.8 Gy/day; total dose, 45 Gy) was
      administered concurrently with courses 3 and 4 of chemotherapy in patients with
      limited-stage small-cell lung cancer. The combination of paclitaxel 200 mg/m2,
      carboplatin to an AUC of 6.0, and extended-schedule oral etoposide 50 or 100 mg
      alternating days 1 through 10 is highly active and well tolerated in patients
      with small-cell lung cancer. The regimen can be administered concurrently with
      radiation therapy with no unusual side effects, although a minority of patients
      develop esophagitis. Median survival rates in patients with both extensive- and
      limited-stage disease compare favorably with other reported regimens.

PMID- 9516610
TI  - The role of carboplatin in the treatment of small-cell lung cancer.
AB  - Lung cancer is the leading cause of death due to cancer in the United States, and
      approximately 178,100 new cases were estimated to occur last year. Small-cell
      lung cancer (SCLC) accounts for approximately 17% to 25% of all lung cancers. Due
      to its aggressive nature and rapid proliferation rate, small-cell lung cancer is
      usually widespread at diagnosis. Therefore, chemotherapy is the cornerstone of
      therapy for this disease. Cisplatin (Platinol) is an active chemotherapeutic
      agent used to treat small-cell lung cancer, but its toxicity, including nausea
      and vomiting, nephrotoxicity, neurotoxicity, and ototoxicity, has led to the
      investigation of combination regimens with different toxicity profiles.
      Carboplatin (Paraplatin), a derivative of cisplatin, has far less nonhematologic
      toxicity, although myelosuppression may be slightly greater than that observed
      with cisplatin. The reduced toxicity and equivalent efficacy of carboplatin have
      resulted in the increased use of carboplatin-based regimens to treat small-cell
      lung cancer. Phase I and II trials of carboplatin as single-agent treatment for
      small-cell lung cancer resulted in overall response rates of approximately 60%
      for previously untreated patients and 17% for those who had received prior
      therapy. New combination chemotherapy regimens that include carboplatin may
      improve survival in patients with small-cell lung cancer and potentially cure
      those patients with limited disease. Further investigation of carboplatin and
      other new agents is warranted.

PMID- 9516612
TI  - Continuing controversies in staging NSCLC: an analysis of the revised 1997
      staging system.
AB  - The 1997 revision of the lung cancer staging system has added very little to
      disease staging, and many changes have been totally unnecessary. Before the next
      revision of the staging system, anticipated in the year 2007, a worldwide effort
      to collect accurate data bases and analyze a variety of T, N, and M prognostic
      factors as well as the newer biologic factors is required to define more
      accurately the clinical and pathologic stages of lung cancer according to
      prognosis. This approach would allow a more rational consideration of changes in
      TNM staging. As well, a single, universally accepted lymph node map is needed
      desperately to unify staging concepts worldwide.

PMID- 9516611
TI  - Small-cell lung cancer: a perspective on the past and a preview of the future.
AB  - Despite advances in the treatment of small-cell lung cancer during the 1970s,
      with the use of combination chemotherapy, and in the 1980s, with the combination
      of etoposide and cisplatin plus concurrent radiation therapy, treatment success
      seems to have reached a plateau in the current decade. Research should now be
      directed into three areas: (1) strategies to prevent the development of second
      cancers, one of the major causes of death in people "cured" of their first
      primary cancer; (2) introduction of new agents such as paclitaxel (Taxol) and
      other newer chemotherapeutic drugs into clinical trials, particularly in
      conjunction with radiation therapy in limited disease; and (3) development of new
      therapeutic approaches, such as the modulation of drug resistance, molecular
      biology interventions, and monoclonal antibody therapy, strategies that are based
      on increased understanding of small-cell lung cancer biology. Although it is
      doubtful that any single strategy will be curative, selective approaches that
      exploit new research findings in conjunction with moderately effective, more
      conventional treatments might allow us to raise remission and survival rates
      significantly.

PMID- 9516613
TI  - The role of prognostic factors and oncogenes in the detection and management of
      non-small-cell lung cancer.
AB  - Like other epithelial tumors, non-small-cell lung cancer (NSCLC) is a result of a
      series of genetic and epigenetic changes that eventually progress to invasive
      cancer. The order and timing of these changes, involving specific chromosomal
      locations, oncogenes, and tumor-suppressor genes, have become important areas of
      translational research. It is hoped that this research will lead to "very early"
      diagnosis and "very early" treatment of non-small-cell lung cancer, and to the
      identification of patients with poor prognostic tumor characteristics who may be
      helped by additional treatment. The recognition of persons with inherited
      predisposition to lung cancer is also on the horizon, and, together with the
      molecular characterization of lung cancer, brings with it a promise of improved
      treatment results.

PMID- 9516614
TI  - Issues in nonoperative management of locally advanced non-small-cell lung cancer.
AB  - The challenge for oncologists treating patients with stage III non-small-cell
      lung cancer (NSCLC) is to optimize a treatment strategy using nonsurgical
      therapies. The recognition that chemotherapy response rates for patients with
      previously untreated locally advanced NSCLC are higher than for those with
      metastatic tumors led to the testing of induction chemotherapy prior to thoracic
      radiotherapy. The regimen of induction vinblastine and cisplatin followed by
      standard thoracic radiotherapy is considered by many to be the optimal regimen
      against which future nonsurgical approaches should be tested. In a trial
      conducted by the European Organization for the Research and Treatment of Cancer,
      a significant survival advantage favored daily low-dose cisplatin/radiotherapy
      and weekly cisplatin/radiotherapy over radiotherapy alone. Presumably, the
      simultaneous delivery of low-dose cisplatin with radiotherapy enhanced local
      tumor response, and the use of higher drug doses in the induction regimens
      deterred the progression of micrometastatic disease. The principal disadvantage
      of concomitant therapy is the enhancement of normal tissue toxicity, both
      hematologic and esophageal, resulting in unnecessary patient morbidity and
      attenuation of radiotherapy and/or chemotherapy delivery. The current phase III
      Radiation Treatment Oncology Group trial seeks to determine the risk/benefit
      ratio of concurrent versus sequential delivery of chemoradiotherapy as well as
      the additional value of oral etoposide in this multimodality regimen. Accrual
      will be completed in 1998. There is also increasing interest in interdigitating
      systemic agents that have been established to be more active in metastatic NSCLC
      than cisplatin/etoposide with thoracic radiotherapy for stage III disease. Phase
      I/II trials using agents like carboplatin and paclitaxel with thoracic
      radiotherapy are summarized, as are plans for phase III testing.

PMID- 9516615
TI  - Recent advances with chemotherapy for NSCLC: the ECOG experience. Eastern
      Cooperative Oncology Group.
AB  - Management of disseminated non-small-cell lung cancer has changed over the past
      10 years. Newer agents, such as vinorelbine (Navelbine) and paclitaxel (Taxol),
      have been shown to modestly improve survival in patients with advanced disease
      when administered in conjunction with cisplatin (Platinol). Compared with older
      regimens consisting of cisplatin and a Vinca alkaloid or a podophyllotoxin, the
      newer regimens yield a 10- to 15-week improvement in median survival and an
      additional 10% to 15% in 1-year survival. Based on these results derived from
      randomized trials, it appears that metastatic non-small-cell lung cancer patients
      with good performance status should be treated with regimens containing either
      vinorelbine or paclitaxel in conjunction with cisplatin.

PMID- 9516616
TI  - One-hour paclitaxel plus carboplatin for advanced non-small-cell lung cancer.
AB  - We report here the preliminary results of a large phase II multicenter study done
      in the community setting, using paclitaxel (Taxol) (given by 1-hour infusion)
      plus carboplatin (Paraplatin) to treat patients with advanced non-small-cell lung
      cancer (NSCLC). In this study, 155 chemotherapy-naive patients with stage IIIB,
      stage IV, or recurrent metastatic non-small-cell lung cancer received the two
      drugs in 21-day cycles. Paclitaxel 225 mg/m2 was given by 1-hour intravenous
      infusion followed immediately by carboplatin at a targeted area under the
      concentration-time curve of 6.0 (calculated according to the Calvert formula).
      Colony-stimulating factors were not used routinely. Objective responses occurred
      in 53 of 155 patients (34%) (53 of 144 [36%] evaluable patients) including three
      complete responses and 50 partial responses. Fifty-two other patients had stable
      disease at initial reevaluation. The median survival among all 155 patients was 8
      months; the 1-year survival rate was 42%, and the 2-year survival rate was 20%.
      Leukopenia and cumulative peripheral neuropathy occurred consistently but rarely
      were severe or affected the course of therapy. One patient died due to sepsis.
      Other grade 3 and grade 4 toxicities were uncommon. This paclitaxel-carboplatin
      combination chemotherapy appears to be a relatively convenient, safe, and active
      regimen in advanced non-small-cell lung cancer.

PMID- 9516617
TI  - Paclitaxel/carboplatin in the treatment of non-small-cell lung cancer.
AB  - Chemotherapeutic intervention in advanced and metastatic non-small-cell lung
      cancer (NSCLC) has changed over the past 2 decades. The improvements offered by
      cisplatin (Platinol)-based regimens, though significant in terms of survival and
      quality of life, were modest at best. Carboplatin (Paraplatin), which possesses a
      toxicity profile favorable to that of its parent analogue cisplatin, yielded
      survival rates superior to that of the cisplatin-combination chemotherapy arms in
      a large randomized study of patients with metastatic non-small-cell lung cancer.
      With the introduction of taxanes in the early 1990s, paclitaxel (Taxol)
      demonstrated single-agent activity of 21% to 24%, with a 40% 1-year survival rate
      in metastatic disease. The next generation of phase I/II studies evaluated the
      efficacy of paclitaxel in combination with carboplatin. Results with this regimen
      have shown substantial promise, and 1-year survival rates as high as 54% have
      been reported. Full doses of both agents have been combined without any
      additional toxicity, and there appears to be a dose-response effect with
      paclitaxel. The combination of paclitaxel and carboplatin has been incorporated
      as the investigational arm of all the ongoing multicenter and cooperative group
      studies. While the results from these randomized studies are awaited, this
      combination has become the most widely used regimen in community practice for
      patients with non-small-cell lung cancer. It is also being evaluated for
      treatment at earlier disease stages, in the setting of minimal tumor burden, and
      in combined-modality regimens.

PMID- 9516618
TI  - Paclitaxel, carboplatin and radiation therapy for non-small-cell lung cancer.
AB  - Preclinically, the taxanes appear to potentiate radiation more effectively than
      do the platinum compounds. In our phase I trial (LUN-17) in patients with
      advanced non-small-cell lung cancer, we defined the maximum tolerated dose and
      toxicity profile of concomitant radiation and paclitaxel (Taxol). We then
      conducted a series of phase II clinical trials in patients with stage III A or
      stage III B non-small-cell lung cancer to explore the role of paclitaxel in a
      combined-modality approach; these trials were based on the very low paclitaxel
      concentrations needed to enhance radiation in the phase I trial and the
      relatively high response rate achieved. Our LUN-27 trial of weekly paclitaxel and
      concurrent radiation for 6 weeks with no adjuvant chemotherapy produced
      substantial response and survival rates with acceptable toxicity. LUN-56 added
      weekly carboplatin (Paraplatin) during the initial concurrent phase as well as
      two cycles of standard-dose paclitaxel and carboplatin. The ongoing LUN-63 phase
      II study delivers concurrent weekly paclitaxel and carboplatin with
      hyperfractionated radiation, followed by two cycles of adjuvant paclitaxel and
      carboplatin, to further improve local control and overall survival. We are
      currently extending the investigation of concurrent weekly paclitaxel plus
      radiation in a large-scale, three-arm, randomized phase II trial. To date,
      toxicity in all trials has been acceptable and compares favorably with other
      regimens. The major side effect, esophagitis, occurs predictably and is managed
      easily, abating shortly after therapy is completed. The rates of overall response
      and 1- and 2-year survival are very encouraging, and phase III evaluation is
      warranted.

PMID- 9516619
TI  - Overcoming drug resistance in lung cancer.
AB  - Anticancer drugs have been explored by means of random screening and demonstrated
      to be active against not only hematologic malignancies but also some solid
      tumors. Recent progress in the field of molecular biology has identified many new
      molecular targets for anticancer drugs. In this review, for example, signal
      transduction pathways, which are influenced by newer agents like the taxanes
      (paclitaxel [Taxol] and docetaxel [Taxotere]) and the protein kinase C activator
      gnidimacrin, are evaluated. Efforts under way to integrate these new compounds
      into clinical trials are discussed.

PMID- 9516620
TI  - Future directions in non-small-cell lung cancer: a continuing perspective.
AB  - Non-small-cell lung cancer (NSCLC) will increasingly come under better control as
      the current approaches to therapy are more broadly employed and as new therapies
      are deployed against recently elucidated molecular pathways. In the United
      States, real progress is finally being made in decreasing tobacco consumption and
      in lung cancer incidence. The traditional chemotherapeutic compounds that became
      available earlier this decade (paclitaxel [Taxol], docetaxel [Taxotere],
      gemcitabine [Gemzar], vinorelbine [Navelbine], irinotecan [Camptosar], topotecan
      [Hycamtin], and edatrexate) have all been tested as single agents and as doublets
      with cisplatin (Platinol) and carboplatin (Paraplatin). Paclitaxel with cisplatin
      or carboplatin and vinorelbine, docetaxel, or gemcitabine with cisplatin have all
      demonstrated significant activity that now appears clearly better than the prior
      standard therapy of etoposide (VePesid)/cisplatin. Phase III studies sorting out
      their benefit relative to each other should be completed in the next 1 to 2
      years. To date, no triplet therapy appears better than the corresponding doublet.
      Non-platinum-containing doublets are just completing their first round of
      assessments. Aside from new drugs and applications, the use of "small" molecules
      to inhibit either signal transduction pathways or gene activation is likely to
      accelerate. Most of the newer chemotherapeutic agents can be interdigitated with
      radiation and surgery, although evaluations into sequence and dose issues
      continue. The superior outcomes seen with the newer regimens should translate to
      the adjuvant and preoperative or preradiotherapy settings relatively quickly. It
      is now clear that NSCLC is as responsive to therapy as small-cell lung cancer
      (SCLC) and that outcomes are superior for NSCLC. The enthusiasm for treating SCLC
      displayed by nononcologists and nonthoracic medical oncologists should be shared
      for NSCLC.

PMID- 9516621
TI  - A prospective evaluation of pediatric emergency care during the 1996 Summer
      Olympic Games in Atlanta, Georgia.
AB  - OBJECTIVES: To explore the impact that a temporary influx of millions of people
      can make on the local pediatric emergent and urgent care systems. The spectrum of
      illness was also explored. DESIGN/METHODS: Prospective cohort of patients from
      outside the usual catchment area presenting at two children's emergency
      departments and their satellite urgent care centers during the 1996 Summer
      Olympics. A 13-point survey was completed on each which included general
      demographics, transportation, language, time in the area, chief complaint, past
      medical conditions, diagnosis, and medical complications or problems related to
      their visit. RESULTS: A total of 263 patients met criteria, mean age 6.7 years.
      Twenty-four percent were seen in the tertiary care centers and 76% in urgent
      care. Twenty-three countries with 15 primary languages were represented. Fifty
      one percent were in Atlanta for less than seven days, and 44% were uninsured.
      Most presented with common concerns including; fevers, rashes, respiratory
      difficulty, and minor trauma. Children were sicker than our typical emergency
      department patients, with hospital admission rates two times the usual for the
      tertiary care children's hospital (27% vs 13%) and the county children's hospital
      (7% vs 3%). Nineteen (7.2%) had unusual presentations or difficulty with care.
      Notably, five had language barriers; three had serious chronic conditions of
      unknown detail to the temporary caregiver; two did not bring vital medical
      supplies (ie, spare tracheotomy tube); one mislabeled medications, causing an
      overdose; one had leukemia, needed transfusion, but did not know of the regional
      centers; and one required helicopter transport secondary to traffic. CONCLUSION:
      A large influx of people resulted in a relatively minor impact on the emergent
      care system for children. Care could have been improved if those with chronic
      illnesses were better informed of regional health care centers, essential medical
      needs for travel, and if travel included a physician's medical summary. In
      addition, anticipation of the Olympic Games helped the pediatric emergency
      medicine community improve disaster preparedness, and enhance its working
      relationship with the adult emergency medicine community and the regional poison
      center. Ongoing efforts for disaster preparedness with periodic reevaluation have
      also been established.

PMID- 9516623
TI  - Parental perception of injury prevention practices in a multicultural
      metropolitan area.
AB  - INTRODUCTION: This study was conducted to survey parents of children seen in the
      emergency department regarding parent and child safety-related behaviors,
      parents' perceptions of their children's risks for injury, and educational needs.
      METHODS: The descriptive design involved three questionnaires with age-specific
      items related to children in groups 0-4 years, 5-12 years, and 13-15 years.
      Parents voluntarily completed the questionnaires in the emergency department
      waiting area. Data were analyzed by descriptive statistics, parametric tests, and
      content analysis. RESULTS: The culturally diverse sample included 81% minority
      group representation. Parents tended to underestimate their children's risks for
      injury from motor vehicle crashes. Less than one half of caretakers believed that
      most injuries can be prevented. Only one third of parents listed needs for future
      learning, although parents of younger children listed more needs. High response
      rates were received for knowing how to call 911, use of child car seats and seat
      belts, and smoke detectors in the home. DISCUSSION: Survey results provide
      evidence that parents have misconceptions about childhood injury. Through
      strategic planning, we have expanded our community education programs to focus on
      cardiopulmonary resuscitation and activating the emergency medical system, water
      safety, use of safety helmets, and injury prevention in the home.

PMID- 9516624
TI  - Comparison of wound care practices in pediatric and adult lacerations repaired in
      the emergency department.
AB  - OBJECTIVE: We compared emergency physician's wound care practices in young
      children (< or = 5 years) and adults (> or = 18 years) and the effect of these
      different practices on infection rate and cosmetic appearance. DESIGN: Cross
      sectional study. SETTING: University hospital emergency department that rarely
      uses conscious sedation. PARTICIPANTS: Consecutive patients who presented with
      lacerations over a four-year period. METHODS: Structured closed question data
      sheets that assessed 26 separate wound characteristics were prospectively
      completed at initial presentation and at suture removal. Infection and cosmetic
      appearance were assessed with previously validated scales. chi(2) tests were used
      for categorical variables, t tests for continuous variables. RESULTS: We
      evaluated 3624 patients: 853 children and 2771 adults. Wounds in children were
      more likely to be on the head (86 vs 38%, P < 0.01); linear (88 vs 77%, P <
      0.01); shorter (1.9 vs 3.0 cm, P < 0.01); less often contaminated (4 vs 11%, P <
      0.01); and more commonly caused by blunt injury (69 vs 37%, P < 0.01). With
      respect to treatment, lacerations in children were less likely to receive
      irrigation (53 vs 77%; P < 0.001) but slightly more likely to be scrubbed (50 vs
      45%, P = 0.01). The two groups received similar numbers of sutures per centimeter
      (2.6 vs 2.3). Using logistic regression, the differences in irrigation were not
      explained by the differences in laceration characteristics. Despite less frequent
      irrigation, children had lower wound infection rates (2.1 vs 4.1%; P = 0.004) and
      better cosmetic appearances (optimal score, 75 vs 64%, P = 0.0003). CONCLUSIONS:
      Emergency physicians at our institution are less likely to irrigate lacerations
      in children than adults; however, children had a lower infection rate and more
      favorable cosmetic outcome.

PMID- 9516622
TI  - Planning model of resource utilization in an academic pediatric emergency
      department.
AB  - This study describes a field observation study and use of simulation to quantify
      the effect of patient arrival rate and physician practices on physician idle time
      and patient wait time. The observation study measured actual service (diagnosis,
      therapy, and charting) times for 126 patients. Subsequently, a FORTRAN simulation
      model examined effects of physician practices and patient arrival rate on
      physician utilization and patient wait time. Observations were taken in the
      emergency department of an urban, university-affiliated pediatric teaching
      hospital. Although times for initial diagnostic evaluation (diagnosis), therapy,
      and charting averaged 13.3, 13.8, and 11.6 minutes, respectively, maximum patient
      visits approached six hours. The simulation model showed that, during times of
      frequent patient arrivals, maximum patient wait times increased greatly.
      Additionally, the model predicted that physician idle time persists even during
      periods of frequent patient arrivals and long maximum visit times. Emergency
      department (ED) senior staff (fellows and attendings) often begin treating new
      patients when current patients leave for tests external to the ED. This practice
      increases physician utilization and makes more physician capacity available, but
      it may lead to small additional patient waits if the physician is treating
      another patient when the first patient returns from the external test before
      their original physician becomes free. On the other hand, during periods of high
      patient arrivals, increased physician utilization and reduced idle time result in
      reduced average and expected maximum patient visit times. Unfortunately the
      variability in visit times increased. A very small percentage of patients wait
      longer, owing to additional waits incurred upon returning from external testing.
      Overall, most patients benefit from shorter visits. Finally, the study suggested
      maximum rather than average wait time be considered as a measure of emergency
      department capacity and quality of service provided. Although average wait times
      seemed reasonable, maximum wait times were at times quite long and could impact
      both physician's and patient's perceptions of service quality.

PMID- 9516625
TI  - Nonurgent use of the pediatric emergency department during the day.
AB  - OBJECTIVE: To evaluate the pattern and reasons for nonurgent use of the pediatric
      emergency department (PED) during regular office hours and why primary care
      physicians (PCP) approve such visits. DESIGN: Prospective, cross-sectional,
      observational study. SETTING: Free-standing, university-affiliated children's
      hospital emergency department. PATIENTS: Patients presenting to the PED and
      triaged as nonurgent between June and November 1994, Monday through Friday from
      6:30 am to 6:30 pm, and Saturday 6:30 am to 12:00 noon. MEASUREMENTS:
      Registration and triage information and all communication with the PCP. RESULTS:
      Of 1020 eligible patients, 364 patients and their PCP completed the study. Fifty
      two percent of the study patients were enrolled in a health maintenance
      organization (HMO). This is consistent with the penetration of managed care in
      this community. Most HMO (118 of 191, 62%) and non-HMO enrollees (147 of 173,
      86%) did not call their PCP prior to arrival in the PED. Comparing the reasons
      given by these patients (HMO enrollees versus non-HMO) for not calling, we found:
      convenience (HMO 17% vs non-HMO 4%, P < 0.01), "no identified PCP" (HMO 17% vs
      non-HMO 42%, P < 0.01), and "felt problem was an emergency" (HMO 19% vs non-HMO
      10%, P = 0.03) to be important differences. HMO enrollees received approval for
      the visit 79% of the time. These approvals were mostly after noon, whereas most
      denials occurred before noon. We found a pattern in the reason for approvals.
      Before 3:30 pm, the most common reason was that the PCP "considered the problem
      medically urgent" (48 out of 106). After 3:30 pm, without significant difference
      in the pattern of patient's chief complaints, there was a dramatic change to "a
      full office schedule" (25 out of 45) as the most common reason. CONCLUSION:
      Communication between the patient and PCP prior to the PED visit is poor in the
      study population. Convenience and physician workload appear to be important
      factors in the choice to use the PED for nonurgent problems.

PMID- 9516626
TI  - Spinal subdural abscess in a pediatric patient: a case report and review of the
      literature.

PMID- 9516627
TI  - A dangerous case of colic: anomalous left coronary artery presenting with
      paroxysms of irritability.
AB  - Anomalous left coronary artery originating from the pulmonary artery (ALCAPA) is
      a rare, but potentially lethal, cause for irritability in infancy. We present the
      case of a 12-week-old male infant who was managed as a colic patient for several
      weeks before the diagnosis of ALCAPA was established. A brief review of previous
      case reports demonstrated that paroxysms of irritability can be a presentation of
      this disorder. In the majority of cases the manifestations of ALCAPA can be
      differentiated from other diseases known to cause a infant to be colicky.

PMID- 9516628
TI  - Jaw mass in a pediatric patient.
AB  - The aneurysmal bone cyst is an unusual cause of a jaw mass in children. Left
      untreated, this relatively benign lesion can lead to deformity and destructive
      bone changes. We report a nine-year-old patient with a large untreated aneurysmal
      bone cyst, and briefly discuss the differential diagnosis of head and neck masses
      in children.

PMID- 9516629
TI  - Neurologic injuries associated with all-terrain vehicles and recommendations for
      protective measures for the pediatric population.
AB  - OBJECTIVE: To present data and case studies illustrating the danger, especially
      in the pediatric population, of all-terrain vehicle (ATV) use, and to provide
      recommendations for pediatricians on how to educate parents concerning ATVs.
      DESIGN: Retrospective review of 33 patients with neurologic injuries sustained in
      ATV accidents presenting to one institution over a 40-month period. SETTING:
      Emergency department and neurosurgery service at Arkansas Children's Hospital and
      two other hospitals that make up the University of Arkansas for Medical Sciences.
      PATIENTS: All patients (n = 33) who presented between January 1993 and April 1996
      at the emergency departments with neurologic injuries sustained in accidents
      involving either a three- or four-wheel ATV requiring hospitalization.
      INTERVENTIONS: Depending on the nature of the injury, various treatments, as
      described herein. MAIN OUTCOME MEASURES: Demographic measures, the mechanisms of
      injury, the types of injuries; the current data available regarding the number of
      injuries nationwide; and the precautionary measures parents should be advised to
      take. RESULTS: Ages ranged from four to 68 years (mean, 18; median, 14), 21 of
      the patients were < 16 years old. The predominant age range was 12 to 15 years;
      most common mechanisms of injury were being thrown to the ground, striking a
      tree, and flipping backward. Most injuries were cranial (21) or spinal (11).
      Nationwide, the proportionate number of injuries are decreasing, but the
      consequences remain severe. Using a helmet and restricting the use of these
      vehicles will reduce the number and magnitude of injuries. CONCLUSIONS: Although
      perceived as recreational toys, ATVs can be extremely unsafe, especially for
      children and adolescents; pediatricians should educate parents and patients on
      the dangers of riding these vehicles.

PMID- 9516630
TI  - Acute disseminated encephalomyelitis: an unusual cause of encephalitic syndrome
      in childhood.
AB  - Acute disseminated encephalomyelitis is a rare central nervous system
      demyelinating disease that occurs most frequently in children. It usually runs a
      monophasic course, beginning with fever, headache, and meningeal signs and
      rapidly progressing to coma when appropriate diagnosis and treatment are not
      provided. We report a case of a 14-year-old patient to alert emergency physicians
      to consider acute disseminated encephalomyelitis when presented with any child
      with encephalitic signs with nonspecific cerebrospinal fluid findings, failure to
      detect any causative agent, and only mild alterations on computerized tomography
      scan. The role of magnetic resonance imaging for the diagnosis is emphasized.

PMID- 9516631
TI  - Metoclopramide toxicity in an infant.
AB  - Metoclopramide (4-amino-5-chloro-N-2-methoxybenzamide) is a central and
      peripheral acting dopamine antagonist. It also stimulates motility in the upper
      gastrointestinal tract and increases lower esophageal sphincter pressure. In the
      pediatric population, it is used extensively as an antiemetic and in the
      treatment of gastroesophageal reflux disease. The case of a six-month-old infant
      who was accidentally overdosed with 24 mg (3 mg/kg) of metoclopramide within a
      nine-hour period is presented. The patient demonstrated toxic extrapyramidal
      effects. There have been multiple early reports in the European literature of
      acute extrapyramidal reactions in the pediatric population, but no reports of
      toxicity exist in the current emergency medicine literature.

PMID- 9516633
TI  - Emergency management of pediatric burn victims.
AB  - Pediatric burn injuries present a major challenge to the health care team, but an
      orderly, systematic approach can simplify the initial stabilization and
      management. A clear understanding of the pathology of burn injuries is essential
      in providing quality burn care in the prehospital setting and at the referring
      hospital. After the patient has been rescued from the offending agent, assessment
      of the burn victim begins with the primary survey and life-threatening injuries
      initially addressed first. This is followed by a secondary survey to document and
      treat other injuries or problems. Intravenous access may be established in
      concert with the local/regional medical control and appropriate fluid
      resuscitation begun. Burn wounds should be covered with clean, dry sheets, and
      the patient kept warm with blankets to prevent hypothermia. The patient should be
      transported to the local hospital ED in the most appropriate mode available. At
      the local hospital, it should be determined if the burn patient needs burn center
      care, using the ABA Guidelines. In preparing for and organizing the transfer of
      the burn victim, consideration must be given to the continued monitoring and
      management of the patient during transport. In transferring burn patients the
      same priorities developed for the prehospital management are still operative.
      During the initial assessment and treatment and throughout the transport, an
      adequate airway, breathing, circulation, fluid resuscitation, urine output, and
      pain control must be assured. Ideally, transport of burn victims will occur
      through and organized, protocol driven plan that includes specialized transport
      mechanisms and personnel. Successful transport of burn victims, whether in the
      pre-hospital phase or during inter-hospital transfer, requires careful attention
      to treatment priorities, protocols, and attention to detail.

PMID- 9516632
TI  - Pediatric emergencies in children with psychiatric conditions.
AB  - This article reviews special considerations for children with psychiatric
      conditions when they present with pediatric emergencies. The review spans a
      variety of scientific disciplines and attempts to integrate information that is
      not usually available to the emergency practitioner from a single source; the
      intent is not to be exhaustive on any particular topic but to organize what is
      most relevant to pediatric emergency care. Topics that are discussed include: 1)
      a brief review of true psychiatric emergencies, 2) side effects of psychotropic
      medications that have direct implications for emergency assessment and
      management, 3) neurologic disorders that present with psychiatric manifestations,
      and 4) psychiatric disorders that present with somatic manifestations.

PMID- 9516634
TI  - A wilderness medicine course for pediatric residents.
AB  - OBJECTIVE: To design a structured curriculum to teach pediatric residents about
      wilderness medicine. BACKGROUND: An increasing number of children are involved in
      more rigorous and potentially risky outdoor activities. Despite the breadth of
      exposure characteristic of most pediatric residences, we are aware of no
      formalized syllabus that prepares residents to both treat injuries sustained in
      outdoor pursuits, and help parents and children to prepare safely for such
      activities. METHODS: The first half of the course was designed to teach a broad
      range of topics in wilderness medicine through a series of readings, lectures,
      and field trips. The second half of the course involved a six-day course in
      wilderness skills. RESULTS: Over a three-week period, the major topics of
      wilderness medicine were thoroughly covered. The three residents involved in the
      planning and execution of the course felt that the course succeeded in filling an
      important gap in their pediatric residency training. CONCLUSIONS: The addition of
      a structured wilderness medicine elective to pediatric residencies, with or
      without a field component, may provide a valuable opportunity for pediatric
      residents to broaden their skills and knowledge base to include these
      increasingly important topics.

PMID- 9516635
TI  - Guidelines for pediatric equipment and supplies for emergency departments.
      Committee on Pediatric Equipment and Supplies for Emergency Departments, National
      Emergency Medical Services for Children Resource Alliance.
AB  - Appropriate care for ill and injured pediatric patients cannot be given if
      emergency departments (EDs) are not adequately equipped. Although guidelines for
      equipment and supplies for EDs have been published by national organizations in
      pediatric emergency textbooks and by state emergency medical services for
      children projects, until now there has been no consensus on what constitutes
      minimum equipment and supplies to care for pediatric patients in the ED setting.

PMID- 9516636
TI  - Possible sudden infant death syndrome.

PMID- 9516637
TI  - Resource utilization.

PMID- 9516638
TI  - Diabetes and transport: a potentially bittersweet combination.
AB  - These cases represent a portion of the spectrum of medical issues that may be
      seen in patients with a diagnosis of IDDM. As the first case suggests, knowledge
      of the disease process and an expanded differential diagnosis is imperative when
      acting as medical command for these patients. Interfacility transport does not
      only involve rapid and safe transport between institutions, but must also offer
      the highest level of expertise available for the referring physician and the
      patient. For this reason, we recommend the immediate availability of a senior
      level experienced pediatric physician for involvement in all but the most routine
      pediatric interfacility transports. Rapid recognition at the time of initial
      presentation or transport of the correct diagnosis in patient one may have
      altered potential outcome. Case 2 represents a potential untoward outcome which
      might be potentiated or exacerbated by the care given during transport. Although
      this patient's transport time was short, a similar patient may present who needs
      prolonged transport. The patient might also present to the transport service
      prior to neurologic deterioration. One must be prepared to intervene for all
      potential complications as they arise. Case 3 represents a patient whose physical
      examination suggested more intense therapy was needed than is offered by many DKA
      protocols. It is important to listen to what the patients are trying to tell us,
      rather than relying strictly on protocols or guidelines. While protocols or
      guidelines offer a menu of potential therapies, one must be prepared to vary from
      these guidelines if suggested by the patient's condition. Recognition of delayed
      capillary refill in patient 3 allowed for an increase in fluid administration and
      rapid patient improvement. While not evident with the presented short transports,
      the use of point of care testing in a transport vehicle can be useful for these
      types of patients. The opportunity to closely monitor blood chemistry evaluations
      and gasses can give insight about an ongoing process, suggest therapies, and help
      direct interventions that, in the past, often waited until the patient arrived at
      the receiving hospital. That additional information can be invaluable for the ill
      patient whose outcome may hinge on early recognition of subtle changes with
      subsequent appropriate interventions.

PMID- 9516639
TI  - Comparison of fluoride modified zirconia with ceramic hydroxyapatite for
      preparative scale purification of immunoglobulin from serum albumin.
AB  - The utility of 50 microns fluoride modified zirconia particles as an easily
      cleaned and steam sterilizable low pressure preparative scale stationary phase
      for immunoglobulin purification was investigated and its performance was compared
      with 40 microns ceramic hydroxyapatite type II (cHAp II) particles. The
      equilibrium batch binding capacity of both supports for bovine serum albumin
      decreases monotonically with increase in the adsorption pH, while that for bovine
      IgG is independent of pH, in the pH ranges studied. The dynamic binding capacity,
      as determined by breakthrough analysis, was 29 mg BSA/g zirconia for fluoride
      modified zirconia and 8.6 mg BSA/g cHAp II for cHAp II. Linear gradient
      conditions were developed for the separation of BSA and IgG on fluoride modified
      zirconia. The same separation could be accomplished in a shorter time and with
      better resolution on cHAp II.

PMID- 9516640
TI  - Expression of functional human recombinant interleukin-12 and development of a
      new reliable bioassay by interferon-gamma ELISPOT.
AB  - Interleukin-12 (IL-12) is one of the important cytokines for promoting the
      differentiation and maturation of type 1 T helper cells and facilitating the
      initiation of cell-mediated immune responses. Because of its multi-functional
      roles in anti-tumor and anti-viral immunity, IL-12 is considered a promising
      therapeutic cytokine in immunotherapy against cancer and infectious diseases. To
      evaluate the therapeutic efficacy, an easy and reliable quantitative assay for
      functional IL-12 is essential. Presently, IL-12 concentration is often determined
      by ELISA or RIA, which may or may not correlate with IL-12 biological function.
      Established IL-12 bioassays are based on a time-consuming lymphocyte
      proliferation assay and require freshly isolated peripheral blood lymphocytes.

PMID- 9516642
TI  - Isolation of parvalbumin isotypes by preparative HPLC techniques.
AB  - Parvalbumins are highly stable Ca2+ binding proteins, present in large quantities
      in the sarcoplasmic reticulum in the white muscle of most lower vertebrates and
      fish. The properties of these proteins make them promising antigens for the use
      as a specific biomarker for fish species identification. Parvalbumin isotypes
      were isolated, on a preparative scale level, by use of size exclusion
      chromatography (SEC) and anion exchange HPLC. The utility of this technique, with
      regard to maximizing purified isotypes, is discussed.

PMID- 9516641
TI  - Preparative chromatography of furosemide 1-O-acyl-glucuronide from urine using
      micronized amberiite XAD-2 and its application to other 1-O-acyl-glucuronides.
AB  - Furosemide 1-O-acyl glucuronide (Fgnd) was extracted from the urine following
      oral administration of furosemide. The crude Fgnd was applied to micronized
      Amberlite XAD-2 column (2.5 cm i.d. x 90 cm length, 75-500 microns particle
      size). The purified Fgnd was identified by mass spectrometry and beta
      glucuronidase treatment. This method was also applicable to the purification of
      glucuronide of tolmetin (nonsteroidal anti-inflammatory drug, NSAID), suggesting
      that it was applicable to the other NSAIDs, most of which were known to be
      metabolized to acyl-glucuronides.

PMID- 9516643
TI  - Organic solvent extraction associated with HPLC in the preparation of hemorphins
      from bovine hemoglobin peptic hydrolysate.
AB  - Hemorphins extraction by organic solvents from a hemoglobin peptic hydrolysate
      was investigated. About thirteen solvents were used and only the aliphatic
      alcohols displayed selectivity for hemorphins. The resulting extracted phases,
      analyzed by SE-HPLC, RP-HPLC, and mass spectrometry, proved 1-butanol and 2
      butanol to be the best extracting solvents towards hemorphins. The opioid
      activity test was carried out following each step of extraction and the obtained
      results were in agreement with a purification.

PMID- 9516645
TI  - Families and cancer.

PMID- 9516644
TI  - Semi-preparative separation and purification of taxol analogs by high-speed
      countercurrent chromatography.
AB  - High-speed countercurrent chromatography (HSCCC) was applied to the semi
      preparative separation of taxol and its analogs, such as cephalomannine and 7-epi
      10-deacetyltaxol from the extract of the bark of Taxus yunnannesis. The
      experiments were performed with a quaternary two-phase solvent system composed of
      n-hexane-thyl acetate-ethanol-water through two steps. In the first step, the
      four components were separated into two groups at a volume ratio of 1:1:1:1 and,
      in the second step, two components in each group were separated at different
      volume ratios of 3:3:2:3 or 4:4:3:4. The present method also allows consecutive
      injections with reproducible results. HPLC analysis showed that the purity of the
      four components obtained from a partially purified sample, containing taxol at
      10%, ranged from 85 to 99%. The results indicated that HSCCC can be effectively
      used for the semi-preparative separation and purification of taxol and its
      analogs.

PMID- 9516646
TI  - Cancer and caregiving: the impact on the caregiver's health.
AB  - A diagnosis of cancer affects not only the patient but also their significant
      others, especially when a lot of care tasks are involved. Some caregivers
      perceive the care as a burden, while others consider it a challenge. In this
      article, findings concerning the impact of cancer caregiving on informal
      caregivers will be described. No consistent results are reported, and little is
      known about patterns of caregiving changes in relation to the course of the
      patient's illness. Attention will be given to factors which have been identified
      as influencing the course and consequences of caregiving. These factors form the
      basis of a conceptual research model for caregivers of cancer patients. As cancer
      progresses, care tasks are generated, which can be perceived by the caregiver as
      either negative (i.e. burden) or positive. Furthermore, these caregiver
      experiences may lead to negative as well as positive effects on the caregiver's
      health and these relationships can be assumed to be bidirectional.

PMID- 9516647
TI  - Family grief therapy: a preliminary account of a new model to promote healthy
      family functioning during palliative care and bereavement.
AB  - The family is usually the primary provider of care for the terminally ill patient
      with cancer or other serious progressive illness. The way in which such a family
      functions is a major determinant of psychological well-being for its members.
      Through screening with the Family Relationships Index (FRI) (Moos and Moos,
      1981), dysfunctional families and those at risk can be identified, and then
      helped to achieve better family functioning, thus improving psychosocial outcome
      of their grief. In this paper, we describe the techniques and themes involved in
      the application of our empirically developed model of family grief therapy,
      designed as a preventive intervention for use in the setting of palliative care
      and bereavement.

PMID- 9516648
TI  - Gender differences in psychological adaptation and coping in parents of pediatric
      cancer patients.
AB  - This study investigated differences in psychological distress and coping styles
      between fathers and mothers of pediatric cancer patients, over a 1-year time
      period. Also examined were (dis)similarities in couples in distress and coping,
      and the relationship between (dis)similarities in coping and psychological
      functioning of both members of a couple. Parents (n = 124, 62 couples) were
      assessed at diagnosis, at 6 and 12 months. Fathers and mothers experienced higher
      levels of psychiatric symptomatology and psychological distress at diagnosis than
      men and women of a normgroup. Distress declined significantly with time. Although
      parents did not report more symptoms than the normgroup 12 months post-diagnosis,
      they still were psychologically out of balance. Contrary to findings in the
      general population, no differences were found between fathers and mothers in
      psychiatric symptoms or psychological distress on any of the measurements. Only a
      few gender differences in coping were found. Fathers used more active-problem
      focusing at diagnosis and a less palliative reaction pattern at 12 months than
      did mothers. Mothers used more social-support seeking on all measurements. A
      tendency for similarity in the use of the coping styles within couples was found.
      Discrepancies in coping in couples were positively related to distress in fathers
      at diagnosis. However, 12 months later, the more discrepant the couples were in
      their coping preferences the more distress the mothers indicated.

PMID- 9516649
TI  - Couples' adjustment to breast cancer and benign breast disease: a longitudinal
      analysis.
AB  - A comprehensive comparison of couples' adjustment to benign (n = 73 couples) and
      malignant breast disease (n = 58 couples) at the time of diagnosis and at two
      follow-up assessments at 60 days and 1 year is reported. Specific objectives were
      to: (a) compare the concurrent stress, resources, appraisal, and patterns of
      adjustment of couples in the benign and malignant groups; (b) compare the
      psychosocial responses of patients versus spouses; and (c) determine the amount
      of correspondence in levels of adjustment reported by patients and their husbands
      over time. Multiple instruments with reported reliability and validity were used
      to measure study variables: Smilkstein Stress Scale, Dyadic Adjustment Scale,
      Family APGAR, Social Support Questionnaire, Mishel Uncertainty in Illness Scale,
      Beck Hopelessness Scale, Brief Symptom Inventory, and Psychosocial Adjustment to
      Illness Scale. Mixed design analyses of covariance (ANCOVA) were used to assess
      differences between and among couples and examine changes in study variables over
      time. Significant differences were found in the resources, appraisal, and
      patterns of adjustment reported by couples in the benign and malignant groups.
      Couples facing breast cancer reported greater decreases in their marital and
      family functioning, more uncertain appraisals, and more adjustment problems
      associated with the illness. In addition, there was a high degree of
      correspondence between the levels of adjustment reported by women with breast
      cancer and their husbands over time. Couples who reported high distress or a high
      number of role problems at diagnosis were likely to remain highly distressed at
      60 days and 1 year. Study findings underscore the importance of assisting
      couples, not just patients, to manage the adjustment difficulties associated with
      breast cancer.

PMID- 9516650
TI  - Prospective study of cancer patients and their spouses: the weakness of marital
      strength.
AB  - In a prospective study, 133 married cancer patients and their spouses were
      interviewed within a month of diagnosis and administered three self-reports: The
      Brief Symptom Inventory (BSI) to assess psychological distress, the Impact of
      Events Scale (IES) to assess coping, and the Family Adaptability and Cohesion
      Scales (FACES III) to assess family relations. Patients and spouses were
      moderately distressed. The patient's psychological distress was explained by the
      level of intrusion, by the spouse's psychological distress and cohesion which had
      a protective effect (R2.41). The spouse's distress was explained by intrusion,
      gender and, to some extent, by the patient's distress (R2.41); but cohesion had
      no influence. Only half of the group (as couples) reached the last follow-up
      nearly 2 years later. A disassociation seems to have occurred; family relations,
      as well as partner's distress, did not have an influence on either the patient's
      or spouse's distress. The information gathered at the beginning of the study
      explained about 25% of the distress 2 years later of male patients and their
      wives, and that of female patients but not of their husbands.

PMID- 9516651
TI  - The role of blood platelets in coronary atherosclerosis and thrombosis.

PMID- 9516652
TI  - Randomized controlled smoking cessation study: transient increase in plasma high
      density lipoprotein but no change in lipoprotein oxidation resistance.
AB  - Low plasma levels of high density lipoprotein (HDL) and high levels of low
      density lipoprotein (LDL) as well as smoking are known risk factors in coronary
      heart disease. It has been suggested that oxidative modification renders LDL
      atherogenic. We investigated the influence of smoking cessation on plasma lipid
      and lipoprotein levels and on the ability of lipoproteins to resist oxidation in
      vitro (lag time). A total of 182 healthy smokers who smoked more than 15
      cigarettes per day were randomized to stop smoking (smoking cessation group, n =
      100) or to continue smoking for 4 weeks (control group, n = 82). The smoking
      cessation group was followed up after 26 weeks. After 4 weeks, the HDL level had
      increased from mean +/- SD 1.36 +/- 0.34 to 1.48 +/- 0.40 mmol l-1 (p < 0.001) in
      62 successful quitters, while levels were unchanged in the control group (72
      subjects in per-protocol analysis). However, after 26 weeks there was no change
      in HDL (1.34 +/- 0.36 vs. 1.36 +/- 0.35 mmol l-1) in 29 subjects from the smoking
      cessation group who fulfilled the study. Plasma levels of very low density
      lipoprotein (VLDL), LDL, total cholesterol, triglycerides and oxidation
      resistance of VLDL + LDL did not show significant changes any time during the
      study for either group. Thus, plasma levels of lipids and lipoproteins as well as
      oxidation resistance of lipoproteins seem unaffected by smoking cessation for 26
      weeks.

PMID- 9516653
TI  - The 13C-urea breath test as a predictor of intragastric bacterial load and
      severity of Helicobacter pylori gastritis.
AB  - BACKGROUND: The urea breath test (UBT) has been proposed as the most accurate
      test for diagnosing Helicobacter pylori infection. The aim of this work was to
      evaluate the accuracy of the UBT and to compare the results with histologic and
      endoscopic findings in H. pylori infected patients. METHODS: One-hundred-and
      seventy-two consecutive dyspeptic outpatients were studied by means of endoscopy
      (with histology and culture), UBT (75 mg 13C-urea), and serology. Gastritis was
      classified in accordance with the Sydney criteria. In H. pylori positive
      patients, the bacterial load was assessed semiquantitatively, the number of
      bacteria in histologic specimens being counted. UBT results were expressed either
      as percentage cumulative dose of 13CO2 excreted at 1 h (CD60) or delta over
      baseline at 30' (DOB30). RESULTS: Of 172 patients, 126 (73%) were H. pylori
      positive on histology or culture. Using a cut-off value of 3.3/1000 for DOB30,
      the sensitivity, specificity and accuracy of the UBT were 96%, 93.5%, and 95.3%,
      respectively. A significant correlation was observed between DOB30 values and
      intragastric bacterial load (r = 0.32). Moreover, a significant difference in
      DOB30 values was found between patients sorted by the depth of inflammation
      (chi(2) = 4.36, p = 0.036). No correlation was observed between DOB30 and
      endoscopic findings in H. pylori positive subjects. CONCLUSIONS: The UBT is an
      accurate non-invasive diagnostic tool and can be used to predict both the
      intragastric bacterial load and the severity of related gastritis.

PMID- 9516655
TI  - Terminological problems around "accuracy" and "uncertainty".
AB  - The consistent description and treatment of metrological data in laboratory
      medicine are hampered by the lack of a systematic, universally accepted
      nomenclature and by variations in the conceptual understanding of uncertainty.
      The differences between the classical approach to a result as consisting of a
      true value plus errors and the new approach of a measured corrected value with
      uncertainty based on a detailed uncertainty budget are discussed. The various
      definitions of some relevant concepts, including "accuracy", the new concept
      "trueness", and "precision", are contrasted, and proposed modification are
      presented.

PMID- 9516654
TI  - Elutriation of human alveolar macrophages: influence on cell surface receptor
      expression.
AB  - Centrifugal elutriation has turned out to be a quick and easy to handle method to
      separate alveolar macrophages with high purity in bronchoalveolar lavage fluid.
      However, less is known about the influence of elutriation on the expression of
      cell surface receptors and cell function. We investigated whether the elutriation
      procedure or different temperatures affect the expression of some surface
      receptors. These were selected to reflect different aspects of cell function such
      as phagocytosis (Fc gamma-receptor), antigen presentation (HLA-DR) and
      proliferation (transferrin receptor). We conclude that the centrifugal
      elutriation procedure has no influence on the expression of these functional
      receptors on resting alveolar macrophages. Heat stimulation, however, increased
      the expression of HLA-DR and the transferrin receptors. Summarizing, when working
      with alveolar cells at +4 degrees C elutriation is a quick method which yields a
      high purity of macrophages that are phenotypically unaltered.

PMID- 9516656
TI  - Skeletal muscle magnesium and potassium by gender and hypertensive status.
AB  - The relation between blood pressure and skeletal muscle magnesium and potassium,
      and the relation between these electrolytes and body mass index, blood lipids,
      blood glucose and plasma insulin concentrations were studied in 29 hypertensive
      and 21 normotensive men. In addition, a comparison was made between the
      normotensive men and 37 normotensive women regarding the concentrations of muscle
      potassium and magnesium. Mean skeletal muscle potassium concentration was lower
      and plasma insulin higher in hypertensive compared to normotensives. Systolic and
      diastolic blood pressures were inversely correlated to muscle potassium and
      positively correlated to insulin. Muscle magnesium was positively correlated to
      muscle potassium but not to blood pressure. Muscle magnesium was significantly
      higher in normotensive women, compared to normotensive men. Muscle potassium did
      not differ between the genders.

PMID- 9516657
TI  - Isoforms and levels of transferrin, antithrombin, alpha(1)-antitrypsin and
      thyroxine-binding globulin in 48 patients with carbohydrate-deficient
      glycoprotein syndrome type I.
AB  - Carbohydrate-deficient glycoprotein syndrome type I (CDGS I) is an autosomal
      recessive disease with multiple organ manifestations. The diagnostic biochemical
      marker has been typical carbohydrate-deficient isoforms of transferrin (Tf). Many
      other glycoproteins in blood may show similar defects, but have not been
      systematically studied before. Forty-eight CDGS I patients and 22 controls were
      examined for total concentrations and isoform distribution of Tf, antithrombin
      (AT), alpha(1)-antitrypsin (alpha(1)-AT) and thyroxine-binding globulin (TBG),
      and for the level of carbohydrate-deficient transferrin (CDT). The absolute
      values varied with age. The most frequent persistent quantitative changes were
      reduced levels of AT (97%) and elevated CDT values (100%). Isoforms lacking one
      to eight of four to eight possible sialic acid residues were found in AT, TBG and
      Tf in all cases, with variable intensity and frequency, and in all except one
      patient in alpha(1)-AT. The isoform changes were most constant and pronounced in
      Tf. The other three glycoproteins showed more abnormal heterogeneity in the
      youngest than in the older patients. The results indicated that the biochemical
      defect stabilizes with age, and suggested partial hypoglycosylation rather than
      non-glycosylation of these glycoproteins. Analysis of Tf isoforms is still the
      safest diagnostic marker of CDGS I from full-term birth and over the ages.

PMID- 9516658
TI  - Comparison of tissue oxygen-tension measurements by different devices. An
      experimental study in pigs.
AB  - The aim of this study was to evaluate measurements of subcutaneous oxygen tension
      (PscO2) generated by three different monitors and to compare measurements
      obtained with and without the tonometer technique in a standardized animal model.
      Seven domestic pigs weighing 20-28 kg were anaesthetized and mechanically
      ventilated. A pulmonary artery catheter was inserted for haemodynamic monitoring
      and temperature measuring. An external carotid artery was cannulated for blood
      pressure monitoring and blood sampling. A peripheral venous line was used for
      fluid and drug infusion. The animals were then subjected to hyperoxia and hypoxia
      by varying the inspiratory oxygen fractions (FiO2) between 0.1 and 0.8. Arterial
      and central venous blood gases were analysed at each step of FiO2. Cardiac output
      was determined using a thermodilution technique. Central, subcutaneous and skin
      surface temperatures were measured. Three different devices for subcutaneous
      tissue oxygen-tension (PscO2) measurements were compared: (1) Biogenesis, (2)
      Continucath and (3) Paratrend 7. Continucath was used both with and without
      tonometer simultaneously. Inter Class Coefficient of Correlation between PscO2
      values obtained by the two Continucath sensors was 76% and between Paratrend 7
      and Biogenesis 88%. Absolute values generated by Biogenesis and Paratrend 7 were
      not different. PscO2 values obtained with the Continucath devices were on average
      50% higher than those generated by Biogenesis and Paratrend 7 (p < 0.05).
      CONCLUSIONS: The new Paratrend 7 and the old Biogenesis sensors generate almost
      equal tissue oxygen-tension values in response to changes in arterial oxygen
      tension. The Continucath sensor generates almost 50% higher values compared with
      the Paratrend 7 and Biogenesis sensors, both with and without tonometer.

PMID- 9516659
TI  - Nitric oxide in septic and aseptic meningitis in children.
AB  - To investigate the involvement of nitric oxide (NO) in childhood meningitis, we
      measured the concentrations of NO2- (a stable metabolite of NO) in serial samples
      of cerebrospinal fluid (CSF) from 11 children with septic and 7 with aseptic
      meningitis and 26 control patients without meningitis. The mean concentration of
      NO2- in samples obtained during the early stages of septic meningitis, but not
      aseptic meningitis, was significantly higher than in control samples. Clinical
      and laboratory improvement following administration of antibiotics and
      dexamethasone was associated with a fall in CSF [NO2-] to normal levels in these
      patients. CSF [NO2-] remained almost consistently within the normal range in
      patients with aseptic meningitis. Our findings indicate that NO production is
      enhanced in the CSF compartment of children with septic meningitis and support
      the hypothesis that NO is involved in the pathophysiology of septic meningitis.

PMID- 9516660
TI  - Insulin treatment reduces the increased serum and lung angiotensin converting
      enzyme activity in streptozotocin-induced diabetic rats.
AB  - Serum and lung angiotensin-converting enzyme (ACE) activity is increased in the
      streptozotocin (STZ)-diabetic rat. In the present study, the effect of insulin
      treatment on this increased ACE activity in the STZ-diabetic rat was
      investigated. Serum and tissue ACE activity was determined by radiometric assay
      using [3H]-Hippuryl-glycyl-glycine as substrate. Fifteen days after onset of
      diabetes (n = 16), 8 rats received insulin daily (6-12 units/kg, s.c.) for 33
      days, 8 diabetes rats remained untreated. Control, non-diabetic, rats (n = 8)
      received saline. The baseline serum ACE activity in the control group was 595 +/-
      13 nmol/ml/min and did not change significantly throughout the study. However,
      serum ACE activity in the untreated diabetic rats increased significantly as of
      day 14 post-STZ (650 +/- 24 nmol/ml/min, p < 0.001) compared to the corresponding
      values of the control group and compared to baseline values. Insulin
      administration to diabetic rats starting on day 15 post-STZ caused a gradual
      reduction in serum ACE activity to basal values, being (527 +/- 22 nmol/ml/min)
      at day 47. ACE activity in lungs of untreated diabetic rats was increased by 46%,
      47 days post-STZ. Insulin treatment reduced lung ACE activity to values similar
      to those observed in non-diabetic rats. These changes were associated with
      reduced kidney weight and urine volume. In summary, insulin administration to
      hyperglycaemic rats resulted in a reduction in the enhanced serum and lung ACE
      activity to values seen in non-diabetic rats. Normalizing the activity of the
      renin-angiotensin system may slow or prevent the glomerular hypertension, a major
      factor in the development of diabetic nephropathy.

PMID- 9516661
TI  - A luminometric assay for determination of ethanol in microdialysates.
AB  - In microdialysis, samples from the extracellular fluid are analysed in the
      outgoing dialysate. By adding ethanol to the ingoing perfusate and following its
      exchange in the dialysate, an outflow/inflow ratio is obtained. This ratio has
      been shown to correlate with the tissue blood flow. An automatic luminometric
      ethanol assay that quantifies the light produced from three coupled enzyme
      reactions is described. Alcohol dehydrogenase catalyses the oxidation of ethanol
      with formation of NADH, which is monitored using NADH:FMN oxidoreductase and
      bacterial luciferase. Each assay can be individually calibrated by measuring the
      increased rate of NADH formation through the addition of a known amount of
      ethanol. The linear range of the assay was 0.05-10 mmol l-1 in microdialysate
      samples. The within-run imprecision was 1.4% CV in 10 mmol l-1 samples, and
      ethanol recovery was almost 100%. The assay was applied to microdialysates that
      were generated from probes implanted in the vastus lateralis muscle in fasting
      subjects (n = 12) and perfused with 5 mmol l-1 ethanol at 3 microliter min-1. An
      outflow/inflow steady-state ratio of 27% (range 19-47%) appeared after about 1 h,
      followed by a within-run variability of 4.7% CV (range 2.5-7.7% CV), as
      calculated from samples collected every 15 min up to 4 h after stabilization. In
      conclusion, a sensitive ethanol assay, suitable for studies of microcirculatory
      exchange of solute molecules over the dialysis probe is presented.

PMID- 9516662
TI  - A neuropsychological analysis of schizophrenic thought disorder.
AB  - We examined the relationship of schizophrenic thought disorder, as measured by
      the Thought Disorder Index (TDI), with (1) neuropsychological measures of verbal
      memory, abstraction, executive function, visual memory, and working memory; and
      (2) quantitative MRI measures of prefrontal and basal ganglia structures. TDI
      scores correlated strongly with tests of verbal memory, abstraction and executive
      functions, modestly with tests of working memory, but did not correlate with
      scores on tests of visual memory. Neither TDI scores nor their neuropsychological
      correlates were associated with frontal or basal ganglia magnetic resonance
      imaging (MRI) measures, with the exception of the measures of working memory that
      demonstrated a modest relationship with frontal and basal ganglia structures.
      These findings suggest that schizophrenic thought disorder may be strongly
      related to neuropsychological impairments in verbal memory, abstraction and
      executive functions, and modestly related to problems with working memory in this
      sample of patients.

PMID- 9516663
TI  - Neuropsychological correlates of positive vs. negative schizophrenic
      symptomatology.
AB  - This study attempts to further the validity of the subtype hypothesis in
      schizophrenia by testing the relationship of neuropsychological functions in
      schizophrenics with predominantly positive vs. negative symptoms. The Brief
      Psychiatric Rating Scale (BPRS) was used to parse schizophrenics into positive
      and negative symptom groups, while a neuropsychological test battery was
      administered to both types of patients. The results indicate that positive
      schizophrenic symptomatology is related to frontal executive tasks, whereas
      negative schizophrenic symptomatology is related to mental tracking tasks that
      require motoric and dexterous manipulation. However, the absence of non
      overlapping symptomatic and neuropsychological functioning groups raises the
      possibility that a three or more factor model may be more reasonable for
      reflecting the variety of symptom and neuropsychological patterns in patients,
      rather than the two-type positive vs. negative dichotomy. The results further the
      hypothesis that schizophrenia is not a single disease entity.

PMID- 9516665
TI  - Is early adulthood a critical developmental stage for psychosis proneness? A
      survey of delusional ideation in normal subjects.
AB  - It has been hypothesized that late adolescence and early adulthood might be a
      brain developmental stage favoring the clinical expression of psychotic symptoms
      in psychiatric or neurological diseases. The aim of the present survey was to
      examine the relationship between age and delusional ideation in a sample of
      subjects with no psychiatric disorder. The survey was carried out with the
      Aquitaine Sentinel Network of general practitioners. Consecutive practice
      attenders were invited to complete the PDI-21 (Peters Delusional Inventory 21
      items), a self-report questionnaire designed to measure delusional ideation in
      the normal population. The study concerned 444 patients who had no lifetime
      history of psychiatric disorder and who completed the PDI-21. A principal
      component analysis of the PDI-21 items was performed in order to identify
      delusional dimensions. An age-related decrease in the likelihood to report
      delusional ideas was found, younger subjects scoring higher on most dimensions of
      delusional ideation, such as 'persecution', 'thought disturbance', 'grandiosity'
      and 'paranormal beliefs'. 'Religiosity' was the only dimension positively
      associated with age. The results suggest that there may be a physiological
      neurodevelopmental stage favouring the expression of psychosis proneness in
      normal subjects, and support the hypothesis that the association between age and
      positive psychotic symptoms in functional and organic psychoses may be linked to
      the interaction between normal brain maturational processes and cerebral
      abnormalities involved in the aetiology of functional and organic psychoses.

PMID- 9516664
TI  - Abnormal visual scan paths: a psychophysiological marker of delusions in
      schizophrenia.
AB  - The role of the visual scan path as a psychophysiological marker of visual
      attention has been highlighted previously (Phillips and David, 1994). We
      investigated information processing in schizophrenic patients with severe
      delusions and again when the delusions were subsiding using visual scan path
      measurements. We aimed to demonstrate a specific deficit in processing human
      faces in deluded subjects by relating this to abnormal viewing strategies. Scan
      paths were measured in six deluded and five non-deluded schizophrenics (matched
      for medication and negative symptoms), and nine age-matched normal controls.
      Deluded subjects had abnormal scan paths in a recognition task, fixating non
      feature areas significantly more than controls, but were equally accurate. Re
      testing after improvement in delusional conviction revealed fewer group
      differences. The results suggest state-dependent abnormal information processing
      in schizophrenics when deluded, with reliance on less-salient visual information
      for decision-making.

PMID- 9516666
TI  - Schizophrenia among patients treated for rheumatoid arthritis and appendicitis.
AB  - The widely accepted negative association between schizophrenia and rheumatoid
      arthritis (RA) is based on the results of investigations which sought RA in large
      samples of schizophrenic patients. Using a discharge register, we examined the
      frequency of schizophrenia in a sample of 5626 RA patients. Appendicitis patients
      (n = 5330) were used as a comparison group. The cumulative incidence of hospital
      care with the diagnosis of schizophrenia during 8 years was higher in the RA
      group (0.64%) than in the appendicitis group (0.47%). Schizophrenia was
      significantly more common in the RA group than in the appendicitis group among
      the young. The age-adjusted prevalence of schizophrenia was 0.96% in the RA group
      and 0.51% in the appendicitis group. Because of this unexpected finding, we
      examined the incidence of RA and appendicitis among a birth cohort born in 1966.
      The frequencies of RA and appendicitis among schizophrenic cohort members (n =
      76), cohort members with psychiatric diagnosis other than schizophrenia (n =
      438), and members without psychiatric diagnosis (n = 10503) were similar. These
      findings do not support the negative association between schizophrenia and RA.
      Prolonged institutionalization per se may have been the protective factor against
      RA in the previous studies. The findings also raise the hypothesis that genes
      that predispose to schizophrenia provide protection from appendicitis,
      historically a common cause of mortality.

PMID- 9516667
TI  - Increased soluble interleukin 2 receptor levels in schizophrenia.
AB  - Immunological mechanisms have been implicated in schizophrenia, but laboratory
      results have been variable. We evaluated soluble interleukin 2 receptor (sIL2R
      alpha) levels in sera of Irish patients with schizophrenia. Twenty-seven
      patients, 12 females and 15 males, with schizophrenia or schizophreniform
      psychosis, were sampled, along with 32 controls. Diagnosis was made using the
      Structured Clinical Interview for DSM IIIR. All but one of the patient group were
      in the first fortnight of an acute hospital admission. Soluble IL2R alpha levels
      were measured by ELISA. Soluble IL2R alpha levels were significantly higher (two
      tailed p = 0.0019) in patients (median = 1010.4 pg/ml, range = 748.7-5673.3
      pg/ml) than in controls (median = 792.3 pg/ml, range = 399.6-1479.5 pg/ml). The
      elevated sIL2R alpha levels in an Irish population with schizophrenia are
      consistent with other reports and support the implication of immunological
      mechanisms in this disorder.

PMID- 9516669
TI  - Social skill as determinant of social networks and perceived social support in
      schizophrenia.
AB  - Factors influencing supportive social networks of people with schizophrenia are
      little understood. Data from 46 outpatients with schizophrenia were analysed
      using structural equation modelling to test plausible sets of inter-relationships
      between social skill, social networks, and social support. The data supported a
      tentative model about the causal relationships between variables. Paths showed
      that people with greater social skill had larger social networks, but did not
      necessarily perceive greater support from these networks. Negative symptoms
      accounted for some of the effect of social skill on social networks. Whereas
      groups of single-admission and multiple-admission participants did not differ in
      terms of social skill, social networks, or support, the age of the participants
      influenced their social skill and the size of their social networks. Younger
      participants had greater social skill and larger social networks. The results
      appear to suggest the importance of early intervention for young people with
      first-episode psychosis.

PMID- 9516668
TI  - Niacin skin flush in schizophrenia: a preliminary report.
AB  - The aim of this pilot study was to evaluate a potential skin test for
      schizophrenia based on the effect of aqueous methyl nicotinate (AMN) on the
      production of prostaglandin D2 (PGD2) from skin macrophages and the resultant
      cutaneous capillary vasodilatation. Four concentrations of AMN were applied
      topically to the forearm skin in patients and controls, and any resulting
      vasodilatation was rated as redness after 5 min. The test was carried out on 38
      patients with schizophrenia diagnosed according to DSM-III-R criteria, and 22
      normal control subjects. At all concentrations of AMN, the schizophrenics were
      highly significantly different from the controls. One concentration gave the
      greatest degree of differentiation: at this concentration at 5 min, 83% of
      schizophrenics but only 23% of controls had a zero or minimal response to AMN.
      The skin flushing seen after oral administration of nicotinic acid is due to the
      same reaction, and this has been normal in those with affective illness and
      neurosis; cyclo-oxygenase inhibitors, e.g., aspirin, give a false-positive result
      (failure of vasodilatation). This result is consistent with the concept of
      reduced membrane arachidonic acid levels in schizophrenia. This test may
      contribute to the reliable diagnosis of schizophrenia.

PMID- 9516671
TI  - Lack of association between schizophrenia and HLA DQB1 alleles in a Swedish
      sample.
AB  - Three studies have reported a negative genetic association between schizophrenia
      and HLA DQB1*0602, an allele of the human leucocyte antigen (HLA) DQB1*06 gene.
      In a sample of ethnic all homogeneous Caucasians living in Sweden, the frequency
      of HLA DQB1 alleles in patients with schizophrenia (n = 124) was compared with
      that in a control group (n = 85). No significant differences were found. Together
      with previous investigations, the present study indicates that the reported
      genetic association of DQB1*0602 with schizophrenia may be limited to non
      Caucasians.

PMID- 9516670
TI  - Inter-rater reliability of the neurological examination in schizophrenia.
AB  - Neurological Examination Abnormalities (NEA) are prevalent in schizophrenia, but
      the significance of this is obscured by methodological problems. The Neurological
      Evaluation Scale (NES), the most widely used structured neurological examination
      in schizophrenia research, has had limited study of its inter-rater reliability
      (IRR). An augmented version of the NES was jointly administered (one examiner
      rater and one observer-rater) by three pairs of psychiatrists to two populations
      of patients with idiopathic psychotic disorders. In addition to the ordinal and
      categorical data yielded by the original NES, continuous data were recorded in
      one of the series. Reliability analyses of our populations and a previously
      published study, reveal consistently adequate IRR in 12 of the 26 items assessed,
      and inconsistently adequate IRR in an additional 11. Consistent with studies
      using other NEA schedules, IRR was unacceptably low for some items that rely on
      subjective severity ratings. Certain rare abnormalities, which posed difficulties
      for the estimation of IRR, are probably not generally useful in the study of
      schizophrenia. Reliability estimates of continuous, ordinal and dichotomous data
      were comparable in most cases. We recommend that certain items from the NES be
      deleted, and that other studies of NEA in psychiatry follow similar procedures
      before undertaking further analyses.

PMID- 9516673
TI  - Porphyria and porphyrinology--the past fifteen years.
AB  - The porphyrias are diseases caused by defective biosynthesis of heme. Leavened by
      digressions on porphyria trivia, this article presents selected highlights from
      the last 15 years of research on the chemistry, diagnosis, and treatment of the
      porphyrias. Thanks largely to genetic analysis and new light shed on the magical
      chemistry of heme biosynthesis, this period has seen great advances in the
      understanding of porphyria. Sequence analyses of the genes for all of the enzymes
      required for heme biosynthesis have revealed the porphyrias as highly
      heterogeneous, with multiple mutations underlying each type. As a result of
      technical advances, clinical porphyrin analyses are easier and more detailed, but
      their misapplication to "multiple chemical sensitivity syndrome" or "intoxication
      porphyria" is unfortunate. The prospect of gene therapy shines ever brighter but
      is neither safe nor effective enough to be considered for porphyria. As practical
      spin-offs, porphyrins are in use increasingly for diagnosis and treatment of
      cancer and as herbicides and pesticides. Accounts of alleged porphyria in
      "Prominent People" in the popular press continue to appear, generating fanciful
      misconceptions, often at the expense of patients with these fascinating diseases.

PMID- 9516674
TI  - Acute intermittent porphyria.
AB  - Acute intermittent porphyria (AIP) is transmitted as an autosomal dominant
      disorder with incomplete penetrance. Recent population studies suggest that the
      prevalence of asymptomatic heterozygotes for a mutant AIP gene may be in the
      range of 1 in 2,000. Clinical manifestations include abdominal pain and
      neurological dysfunctions. These symptoms occur during acute attacks, which are
      often precipitated by drugs, alcohol, low caloric intake, or infections.
      Biochemical abnormalities are thought to result from primary defects of
      porphobilinogen deaminase (PBGD; also called hydroxymethyl bilane synthase), the
      third enzyme of the heme synthesis pathway, and consecutive hepatic
      overexpression of the first enzyme of the pathway, 5-aminolevulinate synthase. As
      a result of these enzymatic disturbances, heme precursors are synthesized in
      excess in the liver, and massive amounts of compounds upstream of the enzymatic
      block are excreted in urine. Although the pathophysiology of the disease has not
      yet been fully elucidated, a specific treatment of acute attacks with heme has
      improved the prognosis. The cDNAs and the gene encoding PBGD have been isolated,
      permitting identification of mutations that account for the corresponding
      enzymatic deficiencies. Consequently, DNA analysis improves the accuracy of
      detection of presymptomatic heterozygotes in AIP families, permitting better
      counseling.

PMID- 9516675
TI  - Hereditary coproporphyria.
AB  - Hereditary coproporphyria (HC) is a rare acute hepatic porphyria. Attacks may be
      precipitated by certain drugs, alcohol, infections, or low caloric intake. HC is
      caused by defects in the enzyme coproporphyrinogen III oxidase (copro-ox) which
      converts coproporphyrinogen III (coprogen) to protoporphyrinogen IX (protogen).
      Coprogen is made mainly in the liver and is excreted predominantly in the feces.
      The dramatic increase in coproporphyrin III (copro) excretion (10-200 times
      compared with the control value) with intensive red fluorescence under UV light
      is a specific and easily detectable marker for diagnosis of acute attacks of HC.
      HC is inherited as an autosomally dominant genetic defect. The cDNA and gene
      encoding copro-ox have been isolated recently and mutations have been identified,
      providing critical information concerning molecular heterogeneity and the
      potential for molecular diagnosis. In this review, we describe 10 mutations in
      the copro-ox gene which are spread along six exons. It is postulated that DNA
      analysis of gene carriers and the use of heme arginate for specific treatment
      will improve the care of HC patients dramatically.

PMID- 9516676
TI  - Variegate porphyria.
AB  - Variegate porphyria is an autosomal dominant inherited trait resulting in
      decreased activity of protoporphyrinogen oxidase. It is characterized clinically
      by photosensitive skin disease and a propensity to acute neurovisceral crises.
      The disease is found worldwide but has an exceptionally high frequency in South
      Africa. The gene for human protoporphyrinogen oxidase has been identified and
      sequenced, and several mutations in the protoporphyrinogen oxidase gene sequence
      have been identified. In South Africa, fewer patients now present with acute
      attacks, leaving a greater proportion with skin disease or asymptomatic disease.
      Acute attacks of variegate porphyria appear to be less easily provoked and to be
      milder than those associated with acute intermittent porphyria.

PMID- 9516678
TI  - Acute porphyria: treatment with heme.
AB  - The characterization of porphyrias as disorders of heme biosynthesis leading to
      hepatic heme deficiency and raised formation and secretion of heme precursors
      laid the basis for heme treatment. Although mild attacks sometimes respond to
      glucose administration, severe attacks or symptoms that are likely to progress
      should be treated with heme. The heme compounds used in treatment are hematin and
      heme arginate. In our opinion, heme arginate is preferable to hematin in the
      treatment of acute porphyrias because of its better stability, fewer side
      effects, and better documentation of its benefits.

PMID- 9516677
TI  - Acute porphyrias: pathogenesis of neurological manifestations.
AB  - Four types of hepatic porphyria (acute intermittent porphyria; hereditary
      coprophorphyria; variegate porphyria; delta-aminolevulinate dehydratase
      deficiency porphyria) present clinically with an identical neurological syndrome.
      Symptoms include severe abdominal pain, vomiting, constipation, hypertension,
      tachycardia, and bladder dysfunction. These symptoms have been ascribed to
      autonomic neuropathy. Other symptoms are motor weakness and sensory involvement,
      which correlate with peripheral axonal neuropathy, and mental symptoms occurring
      without clear morphological findings in the cerebrum. The pathogenetic mechanisms
      which lead to the neurological dysfunction have remained poorly understood,
      partly due to the lack of a suitable animal model of these rare disorders. Two
      hypotheses, the possible neurotoxicity of delta-aminolevulinate (ALA) and heme
      deficiency in nervous tissue are discussed and corresponding data from
      porphobilinogen-deaminase deficient mice are presented. The present evidence
      suggests that multiple mechanisms interact in causing the varied symptoms,
      including ALA interaction with GABA receptors, altered tryptophan metabolism, and
      possibly heme depletion in nerve cells.

PMID- 9516679
TI  - Diagnosis of porphyric syndromes: a practical approach in the era of molecular
      biology.
AB  - For cost-effective diagnosis of porphyric syndromes, a logical stepwise approach
      is best. If neurovisceral features suggest an acute porphyric syndrome, a rapid
      screening test for urinary porphobilinogen should be performed. If clinical
      features suggest a cutaneous porphyria, then for solar urticaria and acute
      photosensitivity (suggesting protoporphyria) screening tests for increased
      erythrocytic porphyrins should be done; for vesiculobullous formation (suggesting
      porphyria cutanea tarda, hereditary coproporphyria, or variegate porphyria) a
      screening test for urinary porphyrins should be done. Positive screening tests
      should be confirmed with targeted quantitative testing. Enzymatic assays and DNA
      based testing are not usually needed for rapid diagnosis or management of
      symptomatic subjects, but they are useful for kindred evaluation and genetic
      counseling.

PMID- 9516680
TI  - Porphyria cutanea tarda.
AB  - Porphyria cutanea tarda (PCT) is a skin disease that results from decreased
      activity of uroporphyrinogen decarboxylase (UROD). About 80% of patients have the
      sporadic (type I) form in which UROD deficiency is restricted to the liver.
      Others have familial (type II) PCT in which mutations in the UROD gene are
      inherited in an autosomal dominant pattern with low clinical penetrance. PCT may
      also follow exposure to porphyrogenic chemicals. Clinically overt PCT (types I
      and II) is provoked by liver cell injury, particularly when associated with
      alcohol abuse, hepatitis C infection, or estrogens. Hepatic iron overload is
      common, depletion of iron stores produces remission, and their replenishment
      leads to relapse. In PCT, hepatic UROD is inactivated by a process targeted at
      its catalytic site, which is iron-dependent, requires a heme precursor, and may
      be accelerated by induction of cytochrome P450s. Susceptibility to develop PCT in
      response to common causes of liver injury may be determined by co-inheritance of
      genes that regulate components of this inactivation process.

PMID- 9516681
TI  - Molecular genetics of congenital erythropoietic porphyria.
AB  - Congenital erythropoietic porphyria (CEP), an autosomal recessive inborn error of
      heme biosynthesis, results from the markedly deficient activity of the cytosolic
      enzyme, uroporphyrinogen III synthase (URO-synthase). The accumulation of the
      nonphysiological and pathogenic porphyrin isomers, uroporphyrin I and
      coproporphyrin I, leads to the clinical manifestations of CEP. Disease severity
      in unrelated patients is markedly heterogeneous, ranging from fetal demise or
      severe transfusion dependency throughout life to milder adult cases with only
      cutaneous photosensitivity. To date, 18 mutations causing CEP have been described
      in the URO-synthase gene, including single base substitutions, insertions and
      deletions, and splicing defects. Most mutations have been identified in one or a
      few unrelated families with the exception of C73R, L4F, and T228M which occurred
      in about 33%, 8%, and 7% of the mutant alleles studied, respectively. Prokaryotic
      expression of the mutant URO-synthase alleles identified those with significant
      residual activity, thereby permitting genotype/phenotype predictions for severe
      to milder phenotypes of this clinically heterogeneous disease. As successful bone
      marrow transplantation in severely affected patients has proven curative, current
      efforts are underway to develop hematopoietic stem cell gene therapy for CEP.

PMID- 9516683
TI  - ALAD porphyria.
AB  - ALAD porphyria is an autosomal recessive disorder resulting from a homozygous
      aminolevulinic acid dehydratase (ALAD) deficiency. Because of an almost complete
      lack of ALAD activity, patients excrete a large amount of ALA, but not PBG, into
      urine. The symptoms in this disease are similar to those seen in AIP, but ALAD
      porphyria can be differentiated from AIP by its autosomal recessive, rather than
      dominant, inheritance, by the lack of PBG overproduction, and by markedly
      decreased ALAD activity.

PMID- 9516682
TI  - Protoporphyria.
AB  - Human protoporphyria results from mutations in the ferrochelatase gene. Heritable
      deficiency of ferrochelatase causes overproduction of protoporphyrin IX,
      principally in the erythron. Photosensitivity is a universal feature of
      protoporphyria but hepatic clearance of the hydrophobic protoporphyrin molecule
      with excretion in bile may lead to precipitation within biliary pathways. Thus
      cholestatic injury and protoporphyrin gallstones occur. Minor hepatic
      abnormalities are frequent, but at least 30 patients have been reported with a
      progressive liver disease that requires transplantation. Fulminant hepatic
      disease appears to be recessively inherited in some pedigrees. Hazards of liver
      transplantation include tissue photolysis, hemolysis, and an unexplained
      neurological syndrome, but most of the 15 patients reported after transplantation
      have survived for several months to > 6 years. Aspects of protoporphyria, its
      pathogenesis and contemporary therapeutic strategies are considered, with
      emphasis on hepatic sequelae.

PMID- 9516685
TI  - Case of the season. Synovial sarcoma.

PMID- 9516686
TI  - Schistosomiasis.

PMID- 9516687
TI  - Radiological diagnosis of Chagas' disease (American trypanosomiasis).

PMID- 9516688
TI  - Filarial diseases.

PMID- 9516690
TI  - Malaria.

PMID- 9516689
TI  - The radiological and ultrasound evaluation of ascariasis of the gastrointestinal,
      biliary, and respiratory tracts.

PMID- 9516691
TI  - Toxoplasmosis.

PMID- 9516692
TI  - Sparganosis.

PMID- 9516693
TI  - Babesiosis.

PMID- 9516694
TI  - An immunohistochemical study of innervation of lumbar spinal dura and
      longitudinal ligaments.
AB  - STUDY DESIGN: An immunocytochemical study of nerve fibers in lumbar spinal dura
      and longitudinal ligaments was conducted in New Zealand white rabbits.
      OBJECTIVES: To demonstrate the presence of nerve fibers and to establish the
      presence of nociceptive and sympathetic nerve fibers in lumbar dura and
      longitudinal ligaments. SUMMARY OF BACKGROUND DATA: The role of dura as a source
      of low back pain is still unclear, and the data present a somewhat conflicting
      picture of the nature of nociceptive innervation in this tissue. METHODS: An
      immunocytochemical method was used to study dura and longitudinal ligaments from
      New Zealand White rabbits. RESULTS: Numerous fine nerve fibers and some small
      bundles were demonstrated in both the dura and the longitudinal ligaments. In
      dorsal dura, the fibers were seen at lateral margins running toward midline. In
      ventral dura and longitudinal ligaments, the fibers were seen throughout the
      substance of these tissues. A population of substance P, calcitonin gene-related
      peptide, and tyrosine hydroxylase-reactive nerve fibers were observed in all the
      tissues. In addition, fibers exhibiting nicotinamide adenine dinucleotide
      phosphate diaphorase activity were also observed, indicating the presence of
      nitric oxide in dura. CONCLUSIONS: The results clearly demonstrate an extensive
      distribution of nerve fibers in dura and longitudinal ligaments. The presence of
      a significant number of putative nociceptive fibers supports a possible role for
      these structures as a source of low back pain and radicular pain.

PMID- 9516695
TI  - Influence of muscle morphometry and moment arms on the moment-generating capacity
      of human neck muscles.
AB  - STUDY DESIGN: The function of neck muscles was quantified by incorporating
      experimentally measured morphometric parameters into a three-dimensional
      biomechanical model. OBJECTIVE: To analyze how muscle morphometry and moment arms
      influence moment-generating capacity of human neck muscles in physiologic ranges
      of motion. SUMMARY OF BACKGROUND DATA: Previous biomechanical analyses of the
      head-neck system have used simplified representations of the musculoskeletal
      anatomy. The force- and moment-generating properties of individual neck muscles
      have not been reported. METHODS: A computer graphics model was developed that
      incorporates detailed neck muscle morphometric data into a model of cervical
      musculoskeletal anatomy and intervertebral kinematics. Moment arms and force
      generating capacity of neck muscles were calculated for a range of head
      positions. RESULTS: With the head in the upright neutral position, the muscles
      with the largest moment arms and moment-generating capacities are
      sternocleidomastoid in flexion and lateral bending, semispinalis capitis and
      splenius capitis in extension, and trapezius in axial rotation. The moment arms
      of certain neck muscles (e.g., rectus capitis posterior major in axial rotation)
      change considerably in the physiologic range of motion. Most neck muscles
      maintain at least 80% of their peak force-generating capacity throughout the
      range of motion; however, the force-generating capacities of muscles with large
      moment arms and/or short fascicles (e.g., splenius capitis) vary substantially
      with head posture. CONCLUSION: These results quantify the contributions of
      individual neck muscles to moment-generating capacity and demonstrate that
      variations in force-generating capacity and moment arm throughout the range of
      motion can alter muscle moment-generating capacities.

PMID- 9516696
TI  - Effect of electromyogram-force relationships and method of gain estimation on the
      predictions of an electromyogram-driven model of spinal loading.
AB  - STUDY DESIGN: An experimental study of fatiguing isometric trunk extension was
      conducted to investigate the spinal loading estimated from an electromyogram
      assisted biomechanical model. OBJECTIVE: To evaluate the sensitivity of the model
      outputs to two crucial assumptions: electromyogram-force relationship and method
      of gain estimation. SUMMARY OF BACKGROUND DATA: In the proposed electromyogram
      assisted models of the trunk, the nature of the electromyogram-force relationship
      and the wide variation in reported muscle gains can result in a wide variation in
      estimates of spinal loading. Given the absence of any gold standard for
      validation of muscle forces, the delineation of confidence intervals for the
      estimated loads has become critical. METHODS: Ten subjects performed a fatiguing
      isometric trunk extension while the net muscular torque output and trunk muscular
      activity were measured. An electromyogram-assisted model was used to estimate the
      torque output and spinal loading. Linear and nonlinear erector spinae
      electromyogram-force relationships and three methods for gain estimation were
      investigated: constant gain determined from an initial maximum extension
      exertion, constant gain based on the fatiguing exertion, and a time-varying gain
      from the fatigue test. RESULTS: The predicted torque was not sensitive to the
      electromyogram-force relationship; the nonlinear model produced 10% lower
      estimates of peak spinal compression force and 14% higher estimates of peak
      anterior shear force. The gain determined from an initial calibration exertion
      underestimated the external torque and underpredicted the peak compression force
      by 20%, compared with gains calculated in the fatigue test. CONCLUSION: The
      nature of the electromyogram-force relationship and of the method for estimating
      the gain significantly affect the outcomes of an electromyogram-assisted model of
      spinal loading.

PMID- 9516697
TI  - A motion analysis of the cervical facet joint.
AB  - STUDY DESIGN: The stability of motion segments of human cervical spines was
      sequentially tested as portions of the vertebral anatomy were removed or cut.
      Isolated, individual facet joints were then similarly studied. OBJECTIVES: To
      define the laxity of isolated cervical facet joints and the relative contribution
      of the different components of the vertebral anatomy to the overall stability of
      the cervical spine. SUMMARY OF BACKGROUND DATA: Facet joints are known to be
      important in determining cervical stiffness and mobility. This is the first known
      study in which the biomechanical behavior of isolated cervical facet joints has
      been documented. METHODS: From five fresh frozen human cervical spines, three C3
      C4 and five C5-C6 motion segments were dissected and potted. Rotations and
      translations in response to 10 bending or twisting moments were recorded by
      tracking the motion of a testing plate fixed to the superior vertebrae using an
      articulated arm digitizer. Each motion segment was tested five times, with
      sequential dissections performed as follows: intact; after removal of the
      anterior longitudinal ligament intervertebral disc, and posterior longitudinal
      ligament; after cutting the interspinous ligament; after isolation of the left
      facet joint; and after isolation of the right facet joint. Each testing sequence
      involved applying low and high forces 10 cm from the center of the testing plate
      in each of 10 testing directions. After completion of rotational testing,
      landmarks on the superior vertebral body and facet joints were digitized to
      calculate vertebral translations. RESULTS: Isolated facet joints allowed up to 19
      degrees of flexion, 14 degrees of extension, 28 degrees of lateral bending, and
      17 degrees of rotation. Coupled motions were less in isolated facet joints
      compared with those in intact vertebral bodies. Isolated facet joints allowed up
      to 9 mm of translation between superior and inferior surfaces. CONCLUSIONS:
      Isolated cervical facet joints are highly mobile in comparison with their motions
      within the constraints of intact motion segments; gliding motions of the isolated
      facet to near dislocation is possible before the facet capsule constrains motion.
      Cervical coupled motions are a result of an intact vertebral ring and a
      combination of the two facet joints. The vertebral ring with facet joints and
      capsules all intact is necessary for lateral bending stability and rotational
      stability in the cervical spine.

PMID- 9516698
TI  - Spinal deformity and instability after multilevel cervical laminectomy for
      spondylotic myelopathy.
AB  - STUDY DESIGN: A retrospective radiographic and medical record analysis of 58
      patients. OBJECTIVES: To describe the incidence and consequences of cervical
      spinal deformity and instability after multilevel laminectomy in adult patients
      with myelopathy caused by cervical spondylosis and to determine the usefulness of
      preoperative dynamic roentgenographic films in the prevention of postoperative
      destabilization. SUMMARY OF BACKGROUND DATA: Extensive cervical laminectomy has
      been widely used in the treatment of progressive myelopathy secondary to stenotic
      conditions. Complications of this procedure, including spinal instability,
      accelerated spondylotic changes, postoperative spinal deformity, and constriction
      of the dura mater by formation of extradural scar tissue formation have been
      recognized. However, the frequency of these complications is probably
      overestimated, and their effect on clinical outcome remains unknown. METHODS:
      Fifty-eight patients older than 30 years who underwent a laminectomy at more than
      three levels without fusion for myelopathy secondary to cervical spondylosis were
      reviewed retrospectively with an average follow-up of 3.6 years. Functional
      results were evaluated according to the Japanese Orthopaedic Association's
      scoring system. Lateral views in neutral position, in flexion, and in extension
      of the preoperative cervical roentgenograms were analyzed in comparison with the
      last follow-up films to identify the changes in the curvature of the cervical
      column, in the range of motion of the neck, and in the intervertebral angular
      mobility and anteroposterior displacement of the vertebral bodies and finally to
      quantify the incidence of spinal instability. RESULTS: In 18 patients (31%),
      postoperative changes in the type of cervical spine curvature developed. Fifteen
      patients (25%) had destabilization at one or more levels. Deformities of the
      cervical spine occurring after surgery do not appear to cause symptoms or
      neurologic abnormalities. Destabilization required repeat surgery in 3 patients.
      All the levels appearing to be destabilized on the postoperative films were
      hypermobile on the preoperative dynamic radiographs. Preoperative olisthesis
      Without hypermobility is not a factor of risk in postoperative destabilization.
      CONCLUSIONS: The use of preoperative dynamic radiographs should improve the
      selection of patients undergoing laminectomy for the treatment of multilevel
      cervical cord compression. Dynamic radiographs may also reinforce the need for
      such adjunctive procedures as fusion and instrumentation, to prevent
      postoperative destabilization. Preoperative olisthesis with hypermobility in
      sagittal or horizontal planes must be fused and instrumented.

PMID- 9516699
TI  - Cervical spondylotic amyotrophy. Magnetic resonance imaging demonstration of
      intrinsic cord pathology.
AB  - STUDY DESIGN: Three case reports. OBJECTIVE: To elucidate the pathophysiology of
      cervical spondylotic amyotrophy. SUMMARY OF BACKGROUND DATA: Cervical spondylotic
      amyotrophy is the clinical syndrome in cervical spondylosis characterized by
      severe muscular atrophy in the upper extremities, with an absent or insignificant
      sensory deficit. Pathophysiology of this particular syndrome has not been well
      understood. METHODS: Three cases of cervical spondylotic amyotrophy are presented
      in which magnetic resonance imaging confirmed the intrinsic cord disease as the
      cause of the syndrome. RESULTS: The patients had segmental muscular atrophy of
      the proximal upper extremities, with an absent or insignificant sensory deficit.
      After initial disease progression, the symptoms stabilized for years. Sagittal T2
      weighted magnetic resonance images showed multi-segmental linear high-signal
      intensity within the compressed spinal cord. These high-signal intensity lesions
      appeared to be located at the anterior horns on axial images. The spinal cord
      compression was less severe in the neck-neutral position, but spinal canal
      stenosis increased when the neck was extended. CONCLUSIONS: The results suggest
      that one pathophysiology of this syndrome may be multisegmental damage to the
      anterior horns caused by dynamic cord compression, possibly through circulatory
      insufficiency.

PMID- 9516700
TI  - The value of lumbar spine magnetic resonance imaging in the demonstration of
      anular tears.
AB  - STUDY DESIGN: Retrospective review of magnetic resonance imaging and discography
      in patients investigated for low back pain before spinal fusion. OBJECTIVE: To
      determine the sensitivity of magnetic resonance imaging in the detection of
      painful anular tears manifested by the high-intensity zone. SUMMARY OF BACKGROUND
      DATA: Two studies have produced results showing that magnetic resonance imaging
      has a high specificity for the detection of painful anular tears manifested by a
      high-intensity zone. However, in a recent study, results showed no significant
      correlation between the high-intensity zone and pain reproduction. The
      sensitivity of magnetic resonance imaging in identifying anular tears in a
      symptomatic population has not been determined. METHODS: Anular tears were
      identified in magnetic resonance images by the presence of a high-intensity zone
      in the posterior anulus. The results were compared with the demonstration of
      painful anular tears on discogram, which has been considered the gold standard.
      RESULTS: The study group comprised 58 patients (31 men, 27 women; mean age 42,
      range 21-63 years). One hundred and fifty-two discs were injected and examined by
      discography, and 108 were considered degenerate. Of these, 86 had anular tears
      (54 posterior, 6 anterior, 26 both). Seventy anular tears were associated with
      concordant pain provocation. Twenty-seven high-intensity zones were identified in
      magnetic resonance imaging, of which 24 were associated with pain reproduction by
      discography. The sensitivity, specificity, positive predictive value, and
      negative predictive value of magnetic resonance imaging in the diagnosis of
      concordantly painful posterior anular tears are therefore 26.7%, 95.2%, 88.9%,
      and 47%, respectively. CONCLUSION: These results confirm that the high-intensity
      zone is a marker of a painful posterior anular tear. However, the usefulness of
      this sign is limited by low sensitivity.

PMID- 9516701
TI  - Lateral radiologic evaluation of lateral mass screw placement in the cervical
      spine.
AB  - STUDY DESIGN: Assessment of the value of lateral radiographs in evaluation of
      lateral mass screw placement in the cervical spine. OBJECTIVES: To assess the
      value of lateral radiographs in determining the safe or hazardous locations of
      the tips of screws used in lateral mass screw fixation. SUMMARY OF BACKGROUND
      DATA: Posterior plating with lateral mass screw fixation is frequently used to
      stabilize the cervical spine and improve fusion. Injury to the spinal nerves
      caused by screws that are too long must be identified quickly to minimize
      neurologic complication. No previous radiologic study in which lateral mass screw
      placement was evaluated using lateral radiographs has been reported. METHODS: Six
      cervical spines were removed from embalmed cadavers. Three screws using the Roy
      Camille technique and another three using Magerl technique were placed into the
      lateral mass at C3-C5 in each specimen. Four screw placements under direct
      visualization, including placement of the screw tip staying the ventral cortex
      and 2-mm, 4-mm, and 6-mm overpenetration of the ventral cortex, were performed
      separately on each specimen for each of the two techniques. After each placement,
      a lateral radiograph was taken. Each vertebral body was divided vertically into
      four equal zones with Zone I the most posterior. Another equal zone, posterior to
      the posterior border of the vertebral body was defined as pre-Zone I. The number
      of screw tips seen in each zone were quantified for each placement. RESULTS: In
      the screws placed using the Roy-Camille technique, 77.8% of screws placed without
      perforating the ventral cortex were found in Zone I; 72.2% placed with 2-mm
      overpenetration of the ventral cortex were noted in Zone II; and 61.1% of the
      screws with 4-mm overpenetration of ventral cortex and 77.8% with 6-mm
      overpenetration were located in Zone III. For the use of the Magerl technique,
      44.4% of the screws placed without perforating the ventral cortex were found in
      pre-Zone I; 72.2% of the screws placed with 2-mm overpenetration were located in
      Zone I; and 66.6% with 4-mm overpenetration and 89.7% with 6-mm overpenetration
      were noted in Zones I and II, respectively. CONCLUSIONS: Lateral radiographs may
      be valuable in evaluating lateral mass screw placement. Ideal screw tip positions
      on lateral radiograph for the Roy-Camille technique may be in Zone I, and for the
      Magerl technique may be in pre-Zone I.

PMID- 9516702
TI  - Back pain in primary care. Patient characteristics, content of initial visit, and
      short-term outcomes.
AB  - STUDY DESIGN: Prospective study of patients making primary care visits for back
      pain. OBJECTIVE: To examine the content of primary care visits for back pain in
      patients with little interference of pain with activities at the visit and 1
      month later; high interference of pain with activities at the visit but not 1
      month later; and high interference of pain with activities, both at the visit and
      1 month later. SUMMARY OF BACKGROUND DATA: Advice about resumption of activities
      may be therapeutic for patients with back pain, but little is known about the
      extent to which primary care providers assess and respond to limitation of
      activities in patients. METHODS: Audiotapes of primary care visits for back pain
      were coded for content. Patients indicated their goals for the visit and
      completed measures of pain and the pain's interference with activities, just
      before the visit and 1 month later. RESULTS: In most visits, providers did not
      assess functional limitations related to pain and did not discuss how to resume
      normal activities, although this was a highly rated goal for most patients.
      Providers did not appear to assess or respond to patients differently according
      to how much pain interfered with their activities. However, in patients with high
      interference of pain with activities, there was more discussion of limitation of
      activities and how to return to usual activities among those who improved than
      there was among those who did not improve during the next month. CONCLUSIONS:
      Although back pain frequently is associated with limitation of activity, pain's
      interference with activities is assessed inconsistently in primary care visits.

PMID- 9516703
TI  - The importance of radiating leg pain in assessing health outcomes among patients
      with low back pain. Results from the Veterans Health Study.
AB  - STUDY DESIGN: Cross-sectional data were analyzed from the Veterans Health Study,
      an observational study of patients receiving ambulatory care. OBJECTIVE: To
      develop a method of stratifying patients with low back pain by combining patient
      reports of radiating leg pain with the results of straight leg raising tests.
      SUMMARY AND BACKGROUND DATA: Four hundred thirty-four participants with low back
      pain were identified through patient reports of ever having had low back pain, of
      low back pain that began more than 3 months ago, and of a health-care visit for
      low back pain in the past year. Four hundred twenty-eight patients with low back
      pain were included in the current analysis. METHODS: Participants were mailed a
      health-related quality of life questionnaire and had an interview that included a
      low back pain questionnaire and a straight leg raising test. Patients' reports of
      radiating leg pain and results of the straight leg raising tests were combined
      into four hierarchical groups. This stratification was evaluated in relation to
      responses to the health-related quality of life questionnaire, localized low back
      pain, disability, and use of medical services. RESULTS: The intensity of
      localized low back pain and disability increased from Group 1 (low back pain
      alone) to Group 4 (pain below knee with positive straight leg raising test
      result), whereas health-related quality of life decreased. Group 4 patients were
      5.1 times more likely than were Group 1 patients to use medications for low back
      pain (95% confidence interval 1.2, 22.9), 6.8 times more likely to have a spinal
      magnetic resonance study (95% confidence interval, 2.7, 17.2), and 3.9 times more
      likely to have surgery (95% confidence interval, 1.3, 11.4). CONCLUSIONS: The
      method of measuring correlation performs well in identifying patients with
      different levels of localized low back pain intensity, health-related quality of
      life, and use of services. It may be useful in studies of health outcomes, in
      clinical trials, and in predicting demands on health care resources.

PMID- 9516704
TI  - The influence of desmopressin on blood loss during spinal fusion surgery in
      neuromuscular patients.
AB  - STUDY DESIGN: A double-blind study comparing the effects of desmopressin and a
      placebo (normal saline) on blood loss during spinal instrumentation for
      neuromuscular scoliosis. OBJECTIVE: To determine the effectiveness of
      desmopressin acetate (DDAVP) in reducing operative blood loss in hemostatically
      normal patients undergoing spinal fusion surgery for neuromuscular scoliosis.
      SUMMARY OF BACKGROUND DATA: Desmopressin acetate has been shown to improve
      bleeding times and to provide surgical hemostasis in patients with platelet
      disorders. Its effect in reducing bleeding times in normal patients has been the
      subject of debate in several surgical specialties. Recent observations that DDAVP
      seems to reduce bleeding times and blood loss in patients undergoing spinal
      surgery for neuromuscular scoliosis warranted a more focused analysis on its role
      in this surgical procedure. METHODS: Patients undergoing surgery for
      neuromuscular scoliosis were randomly assigned to receive DDAVP or placebo.
      Bleeding times and plasma clotting factors were measured before the
      administration of the DDAVP or placebo and 60 minutes after. Operative blood loss
      was carefully measured. RESULTS: Although the administration of DDAVP decreased
      overall blood loss by an average of 19% compared with blood loss in the placebo
      group and blood loss per vertebra fused by an average of 15%, these results were
      not statistically significant. CONCLUSIONS: Bleeding time and blood loss seem to
      respond better to DDAVP in some patients, in whom significant decreases were
      observed, than they do in others. The problem is in identifying those patients in
      whom a decrease in bleeding time will be elicited after administration of DDAVP.
      Preoperative administration of DDAVP to such patients should significantly
      decrease operative blood loss.

PMID- 9516705
TI  - Instrumented posterolateral lumbar fusion. Results and comparison with anterior
      interbody fusion.
AB  - STUDY DESIGN: Prospective case series. OBJECTIVES: To assess the results of
      instrumented posterolateral lumbar fusion, using recognized outcome assessment
      techniques, to evaluate the correlation between technical and clinical results
      and the effects of assessment techniques, and to compare the outcome with that of
      anterior lumbar fusion. SUMMARY OF BACKGROUND DATA: Assessments of lumbar spinal
      fusion results have frequently been published in forms that render direct
      comparison difficult and thus have not provided optimal assistance in the
      selection of a preferred method of treatment. METHODS: One hundred and thirty
      five patients with intractable back pain underwent instrumented posterolateral
      lumbar spinal fusion performed by a single surgeon. Review of results was
      undertaken by independent observers, using a recognized outcome assessment
      measure. RESULTS: A solid bony fusion was obtained in 82% of patients. The method
      of outcome assessment profoundly affected the results; whereas 65% of patients
      rated themselves significantly improved by the procedure, only 19% achieved a
      good or excellent result on the Low Back Outcome Score. Patients undergoing a
      second procedure did not do well, and "salvage" surgery is not recommended.
      Compensation status was a significant prognostic factor. Psychological distress
      at review had a profound effect on the disability score and on patient
      satisfaction ratings. Overall, the results were inferior to those in a similar
      series treated by anterior lumbar fusion. CONCLUSION: It is recommended that in
      future studies a recognized outcome score be used and that the analysis
      specifically include compensation status and psychological distress.

PMID- 9516707
TI  - Lumbar spinal root compression caused by Brucella granuloma.
AB  - STUDY DESIGN: A case report of rarely seen extradural brucellosis granuloma
      causing spinal root compression in the lumbar region. OBJECTIVE: To point out the
      possibility of extradural compression caused by brucellosis. SUMMARY OF
      BACKGROUND DATA: Many investigators have indicated that myelopathy or
      radiculopathy caused by irritation or compression by tiny abscess, disc
      herniation, or extradural granuloma may occur in brucellosis. Failure to make the
      correct diagnosis is possible because of the absence of such symptoms of
      brucellosis as fever, sweating, or fatigue and because findings of physical
      examination, radiography, and myelography indicate intervertebral disc
      herniation. METHODS: Review and discussion of the case history are presented.
      RESULTS: Brucella granuloma compressing the right L5 root and dural sac was
      diagnosed on computed tomographic scans and was excised subtotally after
      laminectomy and facetectomy. CONCLUSION: The possibility of extradural
      compression caused by brucellosis should be considered in endemic areas and must
      be differentiated from an intervertebral disc herniation by means of
      agglutination testing and bone scan.

PMID- 9516706
TI  - Spinal abscess and spondylitis due to actinomycosis.
AB  - STUDY DESIGN: Report of a rare case of spinal actinomycosis in a young
      immunocompetent woman. OBJECTIVE: To show the difficulties in diagnosing spinal
      actinomycosis. SUMMARY OF BACKGROUND DATA: Spinal actinomycosis is rare and
      usually occurs as a result of a contiguous (abdominal, pelvic, or thoracic)
      spread of the infection. This localization represents less than 5% of the
      infectious sites and was mainly, before the penicillin era, a postmortem
      discovery. METHODS: A case is reported of a 34-year-old Algerian woman who had
      fever, persistent cough, right-side thoracic pain, and progressive severe back
      pain. Radiographs, computed tomographic scan, and magnetic resonance imaging
      demonstrated lytic areas on the vertebral bodies of T11 and T12 and a
      paravertebral mass, without disk involvement. A surgical biopsy of T12 and the
      paravertebral abscess was performed. RESULTS: Presence of characteristic sulfur
      granules and gram-positive filamentous bacteria in surgical biopsy tissues and
      isolation of Actinobacillus actinomycetemcomitans in cultures led to the
      diagnosis of vertebral actinomycosis. The patient was virtually free of pain and
      fever after a 3-month regimen of ofloxacin and rifampicin (Rifadine, Marion
      Merell, France) and was without recurrence after 18 months of follow-up.
      CONCLUSIONS: Actinomycosis of the spine, caused by the spread of a paraspinal
      abscess, is extremely rare. The previously poor prognosis has been transformed by
      antibiotics.

PMID- 9516708
TI  - Primary amyloidoma of the spine. A case report and review of the literature.
AB  - STUDY DESIGN: A rare case is reported of primary or idiopathic amyloidoma of the
      spine derived from production of light chain immunoglobulins. The tumor was
      successfully treated by anterior decompression and fusion with a fibula strut
      allograft. OBJECTIVE: To describe a rare case of AL amyloidoma of the spine.
      SUMMARY OF BACKGROUND DATA: Radiographic characteristics of this benign deposit
      are similar to harmful aggressive conditions afflicting the spine. RESULTS: The
      patient returned to full function after the surgery with no evidence of systemic
      amyloidosis or development of multiple myeloma. METHODS: An isolated AL
      amyloidoma of the spine was resected and successfully reconstructed with a fibula
      strut allograft and internal fixation. CONCLUSIONS: Isolated deposits of amyloid
      in the spine occur very rarely. When no evidence of myeloproliferative disease or
      systemic amyloidosis is found, prognosis is excellent. The deposit, when it
      occurs in the spine has a predilection for the thoracic region and can cause
      neurologic compromise, pain, and deformity that is responsive to decompression
      and fusion. The diagnosis of primary amyloidoma requires histologic studies for
      confirmation.

PMID- 9516709
TI  - Lumbar spinal canal stenosis associated with progressive degenerative changes of
      the spine. A case report.
AB  - STUDY DESIGN: Case report. OBJECTIVES: To report a case of spinal canal stenosis
      associated with progressive degenerative changes of the lumbar spine. SUMMARY OF
      BACKGROUND DATA: As far as the authors are aware, there has been no similar case
      reported. METHODS: The clinical features of the case are reported, and the
      pathology is discussed. RESULTS: In a 40-year-old man, spinal canal stenosis
      developed, associated with progressive degenerative changes of the lumbar spine.
      The man underwent posterior decompression and fusion using pedicle screws. The
      surgical results were satisfactory at the time of writing this report.
      CONCLUSIONS: This case presented a peculiar clinical course, which could not be
      categorized under previously reported disorders. It may be a new disease entity
      of spinal canal stenosis. The surgical outcome was satisfactory 2 years, 6 months
      after surgery.

PMID- 9516710
TI  - Lumbar spine duplication presenting as adolescent scoliosis. A case report.
AB  - STUDY DESIGN: A report of a case of lumbar spine duplication with the clinical
      appearance of adolescent scoliosis. OBJECTIVE: To increase knowledge about the
      pathogenesis and treatment of lumbar spinal duplication. SUMMARY OF BACKGROUND
      DATA: Although there have been other reports of lumbar spine duplication of this
      magnitude, these malformations typically are associated with severe neurologic
      abnormalities (dicephalus, myelomeningocele) or gastrointestinal abnormalities
      (omphalocele, neurenteric fistulas). Several investigators have recommended early
      surgical intervention for this abnormality because of the perceived risk of
      progressive neurologic abnormality from tethering of the cord. METHODS: In a 13
      year-old girl who had truncal asymmetry, lumbar spine duplication was noted on
      plain radiographs. A magnetic resonance study was obtained, and the patient was
      observed with conservative treatment for 3 years. RESULTS: Although extensive
      abnormalities were noted on the magnetic resonance images, which were related to
      duplication of spinal cord and vertebral bodies, the patient was neurologically
      intact and remained so until skeletal maturity. CONCLUSIONS: This rare
      malformation typically has severe neurologic sequelae. Conservative management in
      the reported patient did not result in a progressive neurologic lesion at the
      time of skeletal maturity.

PMID- 9516711
TI  - Exercise for patients with low back pain.

PMID- 9516712
TI  - Case report: Complex regional pain syndrome type 2 (causalgia) after automated
      laser discectomy.

PMID- 9516713
TI  - Natural history and nonoperative treatment of lumbar disc herniation.

PMID- 9516714
TI  - Reaction of androst-5-en-17-one with hypobromous acid and its use for synthesis
      of 19-oxygenated 5-ene and 4-en-6-one steroids.
AB  - Reaction of androst-5-en-17-one (1) with hypobromous acid using a short reaction
      time (30 min) along with a careful isolation procedure gave, for the first time,
      the addition product, 5 alpha-bromo-6 beta-hydroxyandrostan-17-one (3), in 43%
      yield. This bromohydrin was much more reactive than 5 alpha-bromo-3 beta-acetoxy
      6 beta-hydroxyandrostan-17-one (4) towards KHCO3 and HClO4. The high reactivity
      of compound 3 was found to be a principal reason for the difficulty in isolating
      this compound by the addition reaction so far. 19-Hydroxyandrost-5-en-17-one (16)
      and androst-5-ene-17,19-dione (18), as well as 19-hydroxyandrost-4-ene-6,17-dione
      (28) and androst-4-ene-6,17,19-trione (29), were synthesized through hypoiodite
      reaction of the bromohydrin 3 as a key reaction.

PMID- 9516716
TI  - Steroidal 5-en-3-ones, intermediates of the transformation of steroidal 5-en-3
      beta-ols to steroidal 4-en-3,6-diones oxidized by pyridinium dichromate and
      pyridinium chlorochromate.
AB  - Oxidation of cholesterol (1a) or pregnenolone (1b) with pyridinium dichromate
      (PDC) in dimethylformamide (DMF) or in dichloromethane (DCM) and pyridinium
      chlorochromate (PCC) in DCM provided cholest-4-en-3,6-dione (2a) or pregn-4-en
      3,6,20-trione (2b). TLC monitoration of the reactions implied that cholest-5-en-3
      one (3a) or pregn-5-en-3,20-dione (3b) and cholest-4-en-3-one (4a) or pregn-4-en
      3,20-dione (4b) might be intermediates. Individual oxidation of 3a or 3b with PDC
      and PCC could give 2a or 2b, but 4a or 4b remained unchanged. Further
      investigation indicated that 4a or 4b was an isomerization product of 3a or 3b on
      silica gel TLC plate rather than really existence in the reaction mixture. These
      results shown steroidal 5-en-3-ones were intermediates of the transformation of
      steroidal 5-en-3 beta-ols to steroidal 4-en-3,6-diones oxidized by PDC and PCC.

PMID- 9516715
TI  - ACTH-mediated glucocorticoid and mineralocorticoid production is inhibited by an
      inositolphosphoglycan and a glycosylphosphatidylinositol-phospholipase C is
      activated by the hormone in mammalian adrenocortical cells.
AB  - In the present paper, we report that an inositolphosphoglycan (IPG), derived from
      a Trypanosoma cruzi glycoinositolphosphoceramide (LPPG), is able to inhibit ACTH
      mediated accumulation of a glucocorticoid, cortisol, in calf adrenocortical
      cells. This IPG is also able to inhibit the stimulation by ACTH of the production
      of the main glucocorticoid, corticosterone and the main mineralocorticoid,
      aldosterone, in rat adrenocortical cells. Nitrous acid deamination confirmed that
      IPG is responsible for this inhibition. In order to study the involvement of
      glycosylphosphatidylinositol (GPI) in ACTH response in rat adrenal cortex, the
      activation of a phospholipase that hydrolyzes GPI (GPI-PLC) was evaluated. It was
      found that the release of alkaline phosphatase, a GPI-anchored enzyme, to the
      extracellular medium is increased in rat adrenocortical cells by ACTH treatment.
      In addition, ACTH stimulates the release of ceramide from the
      glycoinositolphosphoceramide purified from T. cruzi. These data suggest that ACTH
      activates a GPI-PLC in rat adrenal cortex, which is in agreement with our
      previous data in calf adrenocortical cells; thus, the hydrolysis of GPI provoked
      by ACTH takes place in different mammals and the IPG released could inhibit ACTH
      mediated synthesis of aldosterone, corticosterone and cortisol.

PMID- 9516717
TI  - Oral administration of dehydroepiandrosterone to healthy men: alteration of the
      urinary androgen profile and consequences for the detection of abuse in sport by
      gas chromatography-mass spectrometry.
AB  - Dehydroepiandrosterone (DHEA) replacement therapy as compensation for high age
      related decline of DHEA and DHEA sulfate production is a matter of intense
      investigation, since many beneficial effects have been proven, or are suggested
      and expected. Therefore, DHEA abuse by athletes has been considered by the
      International Olympic Committee, which banned the substance recently. As DHEA for
      oral supplementation is easily available, we decided to investigate the effect on
      the urinary androgen profile of administration along this route of a single
      substitution dose of 50 mg. Quantitative analysis by gas chromatography-mass
      spectrometry with selected ion monitoring demonstrated that the drug was readily
      absorbed with 50 to 75% recovery of dosing after 24 h, and with glucuro- and
      sulfoconjugates of DHEA, androsterone, and etiocholanolone as the most abundant
      metabolites. In agreement with reported data found in blood, conversion of
      exogenous DHEA to the principal biologically active androgen, testosterone, was
      low but proven to be real by the administration of deuterium-labeled DHEA and the
      subsequent identification and quantification of deuterium-labeled testosterone. A
      concentration threshold of 300 micrograms/L of DHEA glucuronide is proposed for
      the screening of DHEA abuse in sport, but a single replacement dose can only be
      detected during 8 h. Such a short detection period is the consequence of
      considerable first-pass hepatic metabolism and also of the high interindividual
      variability of circulating and urinary DHEA and DHEA sulfate concentrations.

PMID- 9516718
TI  - Novel microbial hydroxylation of 13-ethyl-17 beta-hydroxy-18,19-dinor-17 alpha
      pregn-4-en-20-yn-3-one.
AB  - The microbial transformation of the dl and the d-enantiomer of 13-ethyl-17 beta
      hydroxy-18,19-dinor-17 alpha-pregn-4-en-20-yn-3-one (1) were investigated. Poor
      yields and poor resolutions were usually obtained for the hydroxylation
      reactions. Transformation of 1 by Cunninghamella blakesleeana gave 6 beta-, 7
      beta-, 10 beta-, 15 alpha-hydroxy derivatives 4, 5, 6, 7, and 6 beta,10 beta
      dihydroxy derivative 8; transformation of 1 by Cunninghamella echinulata afforded
      5, 6, and 8. Biotransformation of dl-1 by Cunninghamella species usually gave 10
      beta-hydroxy product with the low enanitomeric excess or as the racemic form.
      However, C. echinulata was able to efficiently differentiate the two enantiomers
      of 1 in the course of 6 beta,10 beta-dihydroxylation reactions. The d-enantiomer
      of the dl-1 was the better substrate for this type hydroxylation. The 7 beta and
      15 alpha-hydroxylations of 1 by microbial cultures was unusual for 19-nor type
      steroids, and these hydroxylation reactions were presumably due to the presence
      of 17 alpha-ethynyl group.

PMID- 9516720
TI  - Carbenoxolone does not cause a syndrome of mineralocorticoid excess in sheep.
AB  - These studies investigated whether treatment with carbenoxolone (CBX), an
      inhibitor of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD), resulted in an
      enhanced mineralocorticoid response to endogenous or infused cortisol. In
      conscious sodium replete sheep with a parotid fistula, infusion of CBX (40 mg/h
      for 10 days) did not increase mean arterial pressure, or change sodium and
      potassium status or plasma renin concentration, but significantly increased the
      half-life of 1,2[3H] cortisol from 18.6 +/- 4.0 to 38.8 +/- 3.9 min (p < 0.05)
      and reduced the blood clearance rate of cortisol (BCR) from 31 +/- 3 to 15 +/- 4
      L/h (p < 0.01). The reduction in cortisol BCR was associated with reduction in
      cortisol secretion rate from 433 +/- 116 to 181 +/- 79 nmol/h (p < 0.01).
      Cortisol (8 mg/h) for 5 days increased mean arterial pressure (from 83 +/- 2 to
      101 +/- 5 mmHg, p < 0.001) and caused natriuresis, hypokalaemia and
      hyperglycaemia. These responses were unaltered when cortisol was infused from the
      fifth to the tenth day of CBX infusion. These findings suggest that in sheep,
      carbenoxolone is either a less potent inhibitor of 11 beta-HSD2 than in other
      species or 11 beta-HSD2 may not be the only mechanism, which determines the
      specificity of the MR.

PMID- 9516719
TI  - Heck reactions of steroidal alkenyl iodides.
AB  - Heck reactions of some steroid derivatives possessing iodo-alkenyl moiety (17
      iodo-androst-16-ene, 1, 17-iodo-4-aza-4-methyl-androst-16-en-3-one, 2, 17-iodo-4
      aza-androst-16-en-3-one, 3) were carried out in the presence of palladium
      catalysts using various olefins (methyl acrylate, ethyl methacrylate, allyl
      alcohol and allyl acetate) as coupling partners. With methyl acrylate, a side
      reaction was observed: the coupling product underwent a Diels-Alder reaction with
      the excess of methyl acrylate resulting in a six-membered carbocyclic E-ring.
      Reaction conditions of the synthesis of the Heck-product were optimized. Although
      the coupling with allyl alcohol led to the formation of 21-formyl-16-pregnene
      derivatives, the synthesis of the corresponding steroidal unsaturated alcohol
      could be achieved only via hydrolysis of the coupling product of the alkenyl
      iodide with allyl acetate.

PMID- 9516721
TI  - Androgen metabolism in cultured rat renal inner medullary collecting duct (IMCD)
      cells.
AB  - Although the stimulations of renal hypertrophy and renal erythropoietin
      production have been well-known androgen effects in the kidney, recent
      investigative progresses are further providing good evidences for androgen
      regulated gene productions of key enzymes or local hormone substrates important
      to renal cell metabolisms and tubular functions in mouse or rat proximal tubules,
      respectively. It has been also reported that testosterone restores vasopressin
      receptors in medullary collecting ducts of the ageing rat and improves a urinary
      concentrating ability. Therefore in the present study we examined a metabolic
      pathway of androgens in cultured rat renal IMCD cells, which finally determine a
      urinary composition and volume. IMCD cells cultured from kidneys of male Wistar
      rats weighing about 200 g were incubated with serum-free culture media containing
      4 nM [3H] testosterone or [3H] androstenedione for 2-48 h. Radioactive compounds
      in incubation media were then separated by reverse-phase high-pressure liquid
      chromatography (HPLC) and identified mainly on the basis of comparison of
      retention times of standard materials on HPLC. The main metabolites identified in
      testosterone or androstenedione incubation experiment were 5 alpha
      dihydrotestosterone or 5 alpha-androstanedione, respectively. 5 alpha-Reductase
      inhibitor, MK 906, effectively inhibited the formations of these Ring A reduced
      metabolites. These results may suggest that rat renal IMCD cells possess 5 alpha
      reductase activity, thereby converting androgens into their biologically active
      forms in vivo.

PMID- 9516722
TI  - Characterization of high affinity progesterone-binding membrane proteins by anti
      peptide antiserum.
AB  - A chemically synthesized 15-mer oligopeptide derived from the N terminus of high
      affinity progesterone-binding membrane site(s) from porcine liver was used to
      generate site-specific antibodies. Western blotting experiments confirmed the
      specificity of the anti-peptide serum obtained. In further investigations this
      antiserum was used for the identification of the native progesterone-binding
      membrane protein complex that represents an oligomer with an apparent molecular
      mass of about 200 kDa. In temperature-induced Triton X-114 phase separation
      experiments combined with Western-blotting, the progesterone-binding site was
      identified as an hydrophobic (integral) membrane protein. In addition, in Western
      blotting analyses the antiserum reacted with the progesterone-binding or related
      proteins in membrane fractions from a wide array of different tissues in various
      species.

PMID- 9516723
TI  - Artificial neural networks and complex social systems. I. Theory.

PMID- 9516724
TI  - Some reflections on artificial neural networks and statistics: two ways of
      obtaining solutions by working with data.

PMID- 9516725
TI  - Back propagation neural networks.

PMID- 9516726
TI  - Learning vector quantization networks.

PMID- 9516727
TI  - Adaptive resonance theory.

PMID- 9516728
TI  - Fuzzy ArtMap classification network.

PMID- 9516729
TI  - Modular neural networks.

PMID- 9516730
TI  - Radial basis function neural network.

PMID- 9516731
TI  - The Probabilistic Neural Network.

PMID- 9516732
TI  - Logicon Projection Neural Network.

PMID- 9516733
TI  - Self-organizing maps.

PMID- 9516734
TI  - Recirculation neural networks.

PMID- 9516735
TI  - Constraint satisfaction neural networks.

PMID- 9516736
TI  - Self-reflexive networks.

PMID- 9516737
TI  - MetaNet: the theory of independent judges.

PMID- 9516738
TI  - Interactive activation and competition neural networks.

PMID- 9516739
TI  - Hopfield Neural Network.

PMID- 9516741
TI  - Self-recurrent neural network.

PMID- 9516740
TI  - The Boltzmann machine.

PMID- 9516742
TI  - Appendix 1: convergence aspects on back propagation neural networks.

PMID- 9516743
TI  - A convergence demonstration of the weights correction equation in self-reflexive
      networks.

PMID- 9516744
TI  - Convergence aspects of re-entry technique.

PMID- 9516746
TI  - Prenatal exposure to sex hormones: a case-control study.
AB  - The adverse effect of therapeutic use of sex hormones during pregnancy inducing
      pseudohermaphroditism in female offspring has been well known since the early
      1950s. Consequently there has been great concern about the potential effects on
      the offspring of women who use these agents during gestation. Some studies have
      reported an association, particularly of oral contraceptives used during
      pregnancy, with specific types of congenital defects, while this was not observed
      in other studies. Here we present the results of a large case-control study on
      the effect of prenatal exposure to each type of sex hormone. Cases were those
      malformed infants of unknown cause, that is, excluding syndromes and those cases
      with defects that have dominant or recessive inheritance, and those due to
      recognized teratogens. The controls were selected from the same population as the
      cases and are representative of those who, had they developed malformations,
      would have been selected as cases. The results, after controlling potential
      cofounder factors with different logistic regression analyses, do not support the
      hypothesis that prenatal exposure to sex hormones increases the risk of genital
      and nongenital malformations.

PMID- 9516745
TI  - Maternal illness, including fever and medication use as risk factors for neural
      tube defects.
AB  - We investigated if selected maternal illnesses or medications used during the
      periconceptional period increased risk of having neural tube defect (NTD)
      affected pregnancies. We used a population-based case-control study of fetuses
      and liveborn infants with NTDs among 1989-1991 California births. In-person
      interviews were conducted with mothers of 538 (88% of eligible) NTD cases and 539
      (88%) nonmalformed controls, usually within 5 months of delivery. A maternal
      fever or febrile illness episode in the first trimester was associated with an
      increased risk for having a NTD-affected pregnancy, odds ratio (OR) = 1.91 (95%
      confidence interval, 1.35-2.72) for fever and OR = 2.02 (1.20-3.43) for febrile
      illness. Risk estimates were not substantially altered after adjustment for
      maternal age, race/ethnicity, education, vitamin use, and body mass index. Other
      reported illnesses were generally not associated with risks of 1.5 or greater, or
      were too infrequent to adequately estimate risk. An OR of 1.5 or greater was
      observed for maternal use of guaifenesin, OR = 2.04 (0.79-5.28), and an OR of 0.5
      or less was observed for maternal use of calcium-containing medicines, OR = 0.38
      (0.14-1.03). Our findings are consistent with previous reports that suggested
      elevated NTD risks from maternal fever. We could not discriminate, however,
      whether the increased risks observed for maternal fever were indicative of a
      causal relation or due to reporting bias. Our findings suggest that many of the
      illnesses common to reproductive-aged women and the medications commonly used to
      treat them during pregnancy, except, perhaps, for those illnesses that are
      febrile-related, do not appear to substantially contribute to the occurrence of
      NTDs in the population.

PMID- 9516747
TI  - Description of the characteristics of cases with noncontiguous neural tube
      defects identified in a series of consecutive births.
AB  - Van Allen et al. [(1973) Am. J. Med. Genet. 47:723-743] provided evidence for
      multisite closure of the neural tube in humans. Reynolds et al. [(1995)
      Proceedings of the Greewood Genetic Center 14:70-71] and Seller [(1995) J. Med.
      Genet. 32:205-207] described 13 and seven cases of noncontiguous neural tube
      defects (NTDs) respectively and concluded that the presence of noncontiguous NTDs
      cannot be explained on the basis of the model of a single initiation site with
      bidirectional closure. Here we present a series of 14 consecutive infants with
      noncontiguous NTDs, describing their characteristics. These show that
      noncontiguous NTDs are clinically heterogeneous, may have differences in sex
      ratio, and could have causal heterogeneity. The different combinations of closure
      failure defects have shown proportions in our population that are different from
      those in the populations studied by Reynolds et al. and Seller.

PMID- 9516750
TI  - [Breast prosthesis education].

PMID- 9516749
TI  - [ECCO 8: Paris 30 October-2 November 1995 (European Conference on Clinical
      Oncology)].

PMID- 9516748
TI  - Neurulation abnormalities secondary to altered gene expression in neural tube
      defect susceptible Splotch embryos.
AB  - The murine mutant Splotch (Sp) is a well-established model for studying neural
      tube closure defects. In the current investigation, the progression through
      neural tube closure (NTC) as well as the expression patterns of 12
      developmentally regulated genes were examined in the neural tissue of wildtype
      (+/+), Splotch heterozygous (Sp/+), and Splotch homozygous (Sp/Sp) embryos during
      neurulation. The overall growth of the embryos, as measured by the number of
      somite pairs, did not differ significantly between the three genotypes at any of
      the collection time-points. There was, however, a significant delay in the
      progression through NTC for both the Sp/+ and Sp/Sp embryos. A univariate
      analysis on the expression of the 12 candidate genes (bcl-2, FBP-2, Hmx-2, Msx-3,
      N-cam, N-cad, noggin, p53, Pax-3, Shh, Wee-1, wnt-1) revealed that although 11
      were statistically altered, across time or by genotype, there were no significant
      interactions between gestation age and genotype for any of these genes during
      NTC. However, a multivariate statistical analysis on the simultaneous expression
      of these genes revealed interactions at both gestation day (GD) 8:12 (day:hour)
      and 9:00 among Pax-3, N-cam, N-cad, bcl-2, p53, and Wee-1 that could potentially
      explain the aberrant NTC. The data from these studies suggest that a disruption
      in the genes that govern the cell cycle or extracellular matrices of the
      developing neural tube might play a critical role in the occurrence of the NTDs
      observed in Splotch embryos.

PMID- 9516751
TI  - [Hormonal treatment of breast cancer. Implications for quality of life,
      communication and improved therapy].

PMID- 9516752
TI  - [Symposium: "Hereditary breast cancer in clinical practice"].

PMID- 9516753
TI  - [Looked at from both sides].

PMID- 9516754
TI  - [Helping children cope with death. Report of the 3rd International Conference on
      Children and Death in London, Canada].

PMID- 9516755
TI  - [Questions on nutrition].

PMID- 9516756
TI  - Self-management of asthma by adult patients.
AB  - Review of eighteen adult self-management education program evaluations comprising
      clinical trials showed significant achievement in five categories of outcome: (1)
      asthma knowledge; (2) patient perceptions and psychological status; (3) behavior
      related to medicine use, delivery devices and environmental triggers; (4)
      functioning and control of symptoms; and (5) health care use. Not every program
      achieved in all of these categories, probably because interventions of adequate
      power to elicit change in one category of outcome were not powerful enough to
      realize change in another category. An alternative explanation may be that in
      some studies assessment measures were inadequate. Asthma management by patients
      is influenced by their social environment and this aspect of control is least
      well understood. A small qualitative study suggested themes among adult patients
      that describe intra- and interpersonal factors enabling or hindering self
      management including: the ability to acquire information; self-regulation;
      relations with family, friends and coworkers; and, relationships with clinicians.
      Research is needed that provides greater understanding of social environments in
      asthma management, produces standardized measurement tools, and tests more robust
      and theory-based interventions.

PMID- 9516757
TI  - The asthma self-management plan system of care: what does it mean, how is it
      done, does it work, what models are available, what do patients want and who
      needs it?

PMID- 9516758
TI  - Are high generalised and asthma-specific self-efficacy predictive of adequate
      self-management behaviour among adult asthma patients?
AB  - In asthma self-management training, often self-treatment guidelines are included,
      because increased knowledge of asthma alone is not sufficient to change
      behaviour. One way to achieve behavioural changes is by increasing the patient's
      general and asthma-specific self-efficacy expectancies. This refers to beliefs in
      one's capabilities to execute the recommended course of action successfully. We
      wanted to assess whether high generalised and asthma-specific self-efficacy
      expectancies were predictive of adequate self-management and self-treatment
      behaviour. A questionnaire was sent to 4563 persons (18-65 years) who had used
      inhaled medication in 1993. Self-management and self-treatment behaviour were
      operationalised through a hypothetical scenario of a slow-onset asthma
      exacerbation. Of all 1262 asthmatic patients, 39.3% showed adequate self
      treatment behaviour (self-adjusting their inhaled or oral steroids when
      appropriate). Age, asthma-specific outcome expectancies and knowledge were
      predictive of adequate self-treatment. Adequate self-management behaviour (self
      treatment or seeking medical help) was observed in 56.4% of patients. Intentions
      towards self-management and asthma-specific knowledge were significant. Only
      knowledge has a relevant influence on both. Asthma-specific knowledge is the only
      factor that seems relevant for adequate self-management and self-treatment
      behaviour, which might be explained by the hypothetical nature of the scenario.
      When patients experience a real asthma exacerbation, self-efficacy expectancies
      will become more important. Only if knowledge of what to do is present will
      patients be able to show proper self-management and self-treatment behaviour. Our
      results suggest that self-treatment guidelines are only effective in combination
      with patient education, which is important for optimal control of their disease.

PMID- 9516759
TI  - How do patients' views about medication affect their self-management in asthma?
AB  - Successful management of asthma increasingly depends on decisions by patients
      about when and how to use inhalers and tablets prescribed for their asthma
      control. Patients with negative attitudes to asthma medication may not be willing
      to follow their management plan's advice to increase medication when their
      symptoms worsen. Patients do not always believe their doctors' reassurance about
      side effects. Although patient dislike of steroid medication is sometimes
      believed to be the main influence on reluctance to take medication, studies
      suggest that patients dislike taking any medication regularly. Evidence shows
      that patients are no more likely to use a combined inhaler regularly than
      separate steroid and relief inhalers. A proportion of patients with difficult to
      control asthma follow a chaotic self-management style. Attitudes among these
      patients may reflect personal styles, and be difficult to change. Among the
      majority of patients studies now show that patient self-management, and outcomes
      for patients can be improved by structured behavioural interventions. For most
      patients attitudes to medication will follow control of symptoms. The experience
      of successful control by medication, in the ways that patients think are
      important, are most likely to influence patients in positive attitudes to
      medication.

PMID- 9516760
TI  - The comprehensibility of asthma education materials.
AB  - Asthma information pamphlets, brochures and other media materials are produced by
      a range of organisations for a diverse range of educational purposes. It is
      important to understand the principles of preparing appropriate and intelligible
      written material, to increase the probability that they will be more likely to
      improve health outcomes. Asthma patient education material, like many other types
      of health education material, is often written at a reading age above the target
      audience, and is less likely to be comprehended. Attention should be paid to the
      principles of good written communication in the preparation of such material.
      Such material should ideally be used in conjunction with verbal advice, as part
      of a medical consultation or asthma education program. Other asthma education
      media, including public education and mass communications material, should be
      subject to formative evaluation to assess its suitability and relevance for the
      proposed target audience.

PMID- 9516761
TI  - Self-treatment by adults during slow-onset exacerbations of asthma.
AB  - Self-management plans are considered today an essential component of the
      management of asthma. The objective of the present study was (a) to explore
      patients' present practical knowledge of self-treatment of asthma, and (b) to
      provide an assessment of the effect of an educational program on this knowledge
      and self-treatment behaviour. Twenty four adults with asthma from the outpatient
      clinic of the Department of Pulmonary Medicine participated in a self-management
      program. They were provided with explanations on the symptoms and precipitating
      factors of their asthma, on its treatment with medication and their side-effects,
      and with personal written guidelines for self-adjustment of their medication.
      Prior to the program their practical knowledge of adequate self-treatment was
      investigated using a hypothetical scenario of a slow-onset asthma exacerbation.
      The effectiveness of the teaching and training program was evaluated by the
      change in knowledge prior to and 5 months after the program and self-reported
      behaviour of the participants at follow-up. (a) More than 60% of the patients
      lacked practical knowledge of self-treatment of a slow-onset exacerbation of
      asthma. (b) The educational program resulted in a significant increase (47%) of
      this knowledge. (c) Actual self-treatment behaviour, as recorded by the patients
      5 months after completing the educational program, was adequate in only two of
      ten patients, who experienced an exacerbation during the study period. Many
      adults with asthma are deficient in practical knowledge of self-treatment of a
      slow-onset exacerbation. This knowledge was significantly augmented by an
      educational program. Nevertheless actual self-treatment behaviour at follow-up
      was inadequate in the majority of patients.

PMID- 9516762
TI  - Individual versus group education: is one better?
AB  - Individual and small group approaches to delivering patient education have
      differing potential advantages, and various criteria can be used to determine
      which is "better". Individualization of education is possible in either delivery
      format, as is its absence. Limited evidence regarding the relative effectiveness
      and cost-effectiveness of different delivery modes is available from direct
      comparison and meta-analyses of studies comparing either of the approaches with
      no education or the patient's own pre-education status. This evidence supports
      the conclusions that: (1) both individual and group education can improve patient
      outcomes, (2) it is not possible to conclude that the two delivery formats are
      essentially equivalent in effectiveness, and there is some evidence that group
      education may more effective for some outcomes, and (3) wide variation in
      effectiveness exists among programs in both delivery formats. A model continuum
      of asthma education is presented that takes advantage of the respective strengths
      of individual and group delivery.

PMID- 9516763
TI  - Delivering asthma education to special high risk groups.
AB  - Patients at high risk from their asthma and therefore worthy of more focused
      asthma education are those at risk of fatal and near fatal asthma(NFA). In recent
      years the characteristics of these patients have been better defined. The most
      important risk factor appears to be a prior history of NFA. Other important
      features include prior emergency room visits or hospitalization for asthma.
      Excess use of beta-agonists, especially in the absence of inhaled
      corticosteroids, also confers increased risk. High risk groups also share similar
      psychosocial barriers as well as economic deprivation. The benefits of asthma
      education in these groups have been assessed in a number of studies. In general,
      asthma education has been shown to have an impact on these patients. Greater
      effects have been achieved where there has been consistent follow-up by the same
      physician. Patients require frequent reinforcement of their asthma management,
      especially regarding their response to acute exacerbations. A sub-group of
      patients with more severe asthma appear to have a problem perceiving dyspnoea and
      may therefore benefit from peak flow monitoring but the problem of compliance
      with this intervention is significant. Behaviour modification plays an important
      role as does ensuring the patient has adequate resources to purchase medications
      especially the more expensive anti-inflammatory therapy. Future studies should
      focus on optimizing the potential benefits of educating high risk patients as
      they are not only those at greatest risk of death but also consume a
      disproportionate amount of health care resources.

PMID- 9516764
TI  - Evaluation of the long-term effectiveness of three instruction modes for inhaling
      medicines.
AB  - Inhaled medication is important in the treatment of chronic obstructive pulmonary
      disease (COPD). In this paper a comparison of the long-term efficacy of three
      instruction-models is presented. A total of 152 COPD-patients were randomized
      into one of four groups: Personal-, video-, group-instruction and a control
      group. Inhalation technique was assessed by means of checklists, on which
      essential inhalation manoeuvres were identified. Up to 9 months later, 148
      patients returned for follow-up assessment. Prior to instruction 61% of patients
      in the control group had a perfect score on essential actions, compared to 62, 65
      and 53% for those receiving group-, personal- and video-instruction respectively.
      At follow-up these percentages were 49, 97, 75 and 76%. For group-(35%) and video
      instruction (24%) the increase from baseline was significant. Examining the
      different inhalers under investigation, it is striking, that only 24% of all
      patients with a Metered Dose Inhaler (MDI) performed all essential checklist
      items correctly, versus 96% for those using a Diskhaler. The fact that for the
      MDI this percentage improved to 90% post-instruction, shows that time spent on
      instruction, is time well spent. We conclude that group instruction seems
      superior to personal counselling, and equally effective or even better than video
      instruction. Personal instruction should not be dismissed and a combination with
      video instruction might prove to be effective as well.

PMID- 9516765
TI  - Is asthma self-management cost-effective?
AB  - Many clinical studies have shown that self-management and educational programs in
      asthma are effective. However, these programs are costly themselves and could
      also lead to higher drug costs due to higher rates of compliance. On the other
      hand, if better usage of available treatment leads to better asthma control, the
      patients' utilization of other health care resources and absence from work might
      be reduced. An interesting question is therefore whether the self-management and
      educational programs in asthma have been cost-effective. This study holds a
      review of the evidence of cost-effectiveness of self-management and educational
      programs in asthma. Several methodological flaws were detected (for example, a
      common effectiveness, variable is lacking in the literature) and suggestions of
      improvements were given. The overall picture is, however, that self-management
      and educational programs in asthma are cost-effective interventions, both for
      children and for adults. As would be expected, it also seems as if programs
      directed at high risk groups and patients with severe asthma are even more cost
      effective. Costs for absence from work were often excluded, which could lead to
      further societal savings. Also, some studies showed that the effect of the self
      management and educational programs had effects even after the initial year.
      Since most studies only covered the initial year of treatment, the cost
      effectiveness of self-management and educational programs in asthma is likely to
      be underestimated in the reported studies.

PMID- 9516766
TI  - Self management in COPD: one step beyond?
AB  - On the basis of the beneficial health effects of self-management in the treatment
      of other chronic diseases like asthma it might be expected that the active
      participation of COPD-patients in the management of their disease may reduce the
      burden of the disease. Self-management of COPD includes sufficient coping
      behaviour, compliance with inhaled medication, attention to changes in the
      severity of the disease, adequate inhalation technique, and self adjustment of
      the medication in case of exacerbations. The results of a pilot study on the
      effects of self-management in COPD suggest a reduction of morbidity due to COPD.
      The definite place of self-management in the treatment of COPD has to established
      by larger, prospective, controlled trials.

PMID- 9516767
TI  - Postnatal depression: making better use of health visitors and community
      psychiatric nurses.

PMID- 9516768
TI  - Monitoring children's growth: how are we doing?
AB  - This month the Chief Medical Officer's National Screening Committee held its
      first conference on systematic reviews of screening in child health. It was
      managed by the Child Growth Foundation, included an interim report on growth
      screening and posed the question whether children needed more of the same. Tam
      Fry, Honorary Chairman of the Foundation, believes that, as far as growth is
      concerned, they do despite the improvements that have been made since the "new"
      centile charts were introduced four years ago and reported in Professional Care
      of Mother & Child.

PMID- 9516770
TI  - A contribution to the discussion on fetal pain

PMID- 9516769
TI  - The rapid access paediatric clinic: a way to reduce inappropriate admissions to
      hospital.
AB  - With documented evidence of increased numbers of paediatric admissions to a
      reduced number of beds, it is important that children are admitted to hospital
      for appropriate reasons. Some hospitals have set up rapid access or emergency
      consultation clinics to try to avoid unnecessary paediatric admissions. This
      study examined the presenting problem of 451 patients referred by general
      practitioners (GPs) to the paediatric emergency clinic at Southampton General
      Hospital over a five month period, and the outcome for the children in terms of
      investigation, admission or follow-up. The most common presenting problems were
      gastrointestinal (26.8%), respiratory (22.8%) or infectious (19.1%). Cough or
      "chestiness" was the single most common presenting symptom. A total of 328
      investigations was performed. After the clinic visit, 35.3% of children were
      discharged, 18.8% were asked to return to the clinic for a follow-up visit and
      19.1% were admitted to the ward. 16.4% were given a future paediatric outpatient
      appointment, 7.3% were referred for specialist opinion in a different speciality,
      and 6.7% were advised to return to the GP for follow-up. The authors consider
      that the emergency paediatric clinic is appropriately used by GPs referring acute
      and sub-acute problems and believe that local satellite clinics run along similar
      lines would be welcomed by GPs, health visitors and parents. Although there is
      little documented evidence that rapid access paediatric clinics reduce admission,
      the authors consider that unnecessary admission was avoided for many of the
      children seen in the emergency clinic. Prospective studies are needed to confirm
      this.

PMID- 9516771
TI  - What is a milk-free diet and why is it needed?

PMID- 9516772
TI  - Does poor nutrition lead to poor immunity?

PMID- 9516774
TI  - Pulling together for health: 1. CPHVA annual professional conference 1997.

PMID- 9516773
TI  - Childhood migraine: a guide to diagnosis and care.

PMID- 9516776
TI  - [Comprehensive dental care--care of the teeth in homebound elderly is most often
      neglected].

PMID- 9516775
TI  - [Work environment--increasing work in spite of a lot of time pressure. Interview
      by Kirsten Bjornsson].

PMID- 9516777
TI  - [Violence--abuse of the elderly. Interview by Susanne Bloch Kjeldsen].

PMID- 9516778
TI  - [Dying--complete openness when death is near. Interview by Susanne Bloch
      Kjeldsen].

PMID- 9516779
TI  - [Psychiatry--patient diagnosis].

PMID- 9516780
TI  - [Research--only the best do it].

PMID- 9516781
TI  - [Research--seen from the sidelines. Interview by Grethe Kjaergaard].

PMID- 9516782
TI  - [Care of Ilizarov patients].

PMID- 9516783
TI  - [Cancer information--watch your step].

PMID- 9516784
TI  - [Research--ideas depot].

PMID- 9516785
TI  - [Expelled from the job].

PMID- 9516786
TI  - [Nurses' specific responsibility].

PMID- 9516787
TI  - [In the professional organization with leaders].

PMID- 9516788
TI  - [The right to examine documents in one's own case].

PMID- 9516789
TI  - [Pary in a malpractice case].

PMID- 9516790
TI  - [Extenuating circumstances].

PMID- 9516791
TI  - [Why still in such a hurry?].

PMID- 9516792
TI  - [Good experience with memory course].

PMID- 9516793
TI  - [Psychiatry--mental disease nurse].

PMID- 9516794
TI  - [History--a living museum. Interview by Grethe Kjaergaard].

PMID- 9516795
TI  - [Health- and nursing care meeting--stop thinking profession, think of caring
      instead].

PMID- 9516796
TI  - [Health- and nursing care meeting--we did not even have protective clothing].

PMID- 9516797
TI  - [Health- and nursing care meeting--nursing home cannot cope with hygiene].

PMID- 9516799
TI  - [Health- and nursing care meeting--seeing with the 'patient's eyes'].

PMID- 9516798
TI  - [Health- and nursing care meeting--"microscopes are not outdated"].

PMID- 9516800
TI  - [Will we learn from Southeast Asia? Enormous wage differences, censorship, strike
      prohibition, long waiting lists for health care...].

PMID- 9516801
TI  - [Think of good nursing care].

PMID- 9516802
TI  - [Care for the aged--the only human contact from the district nurse?].

PMID- 9516803
TI  - [Israel-Palestine--Zionism and democracy are two incompatible entities].

PMID- 9516804
TI  - [Israel-Palestine--groundless attacks against the state of Israel].

PMID- 9516805
TI  - [Unreasonable Swedish need for EU-adapted education].

PMID- 9516806
TI  - [Labor Tribunal not an end in itself].

PMID- 9516807
TI  - [Living situation of heart patients--long waiting list for revascularization
      increases uncertainty and fear].

PMID- 9516808
TI  - [Warning about dialysis accident].

PMID- 9516809
TI  - [Crying time: 5 hours 10 minutes. Crying infants with food colic easy to handle.
      Interview by Torbjorn Uhlin].

PMID- 9516810
TI  - [When health care changes nurses must exert pressure].

PMID- 9516811
TI  - [Nursing and informatics].

PMID- 9516812
TI  - [Tissue tolerance and the risk of decubitus].
AB  - Based on a review of the literature on prediction and prevention of pressure
      sores, a conceptual scheme is introduced. The three determinants--pressure,
      shearing force and tissue tolerance--are discussed.

PMID- 9516813
TI  - [Nurses' experiences with euthanasia in AIDS patients].
AB  - This article describes the experiences of nurses concerning the activities
      related to euthanasia of patients with aids. The nurses were employed in
      departments where relatively young, mature people wanted to arrange their own
      death. Our findings are based on six in-depth interviews with experienced nurses,
      that are part of a qualitative study into the experiences of nurses in taking
      leave of terminal patients with aids. The research strategy was based on the
      Grounded Theory. In order to analyse the experiences of the nurses, four phases
      were distinguished: set date and time unto application of lethal agent;
      application unto becoming unconscious; unconsciousness to death; death until
      transferring the body from the unit. Feelings that occur when taking leave of the
      patient, if not already taken care of at an earlier instant, play a major role in
      the phase from application to becoming unconscious. The fact that a deadly agent
      is being administered can generate feelings of guilt and anxiety. The period from
      unconsciousness to death is one of waiting. During this period nurses feel
      alienated and alone. The nurses indicated explicitly that an adequate
      preparation, evaluation and support are extremely important.

PMID- 9516814
TI  - [Work and worker reactions in homes for the aged].
AB  - This article describes an investigation of relationships between work
      characteristics and worker reactions in three elderly homes of a Dutch
      foundation. Moreover, main effects as well as moderating effects of some relevant
      individual variables were studied. Variables were measured by means of
      questionnaires; 144 subjects from the caring and household departments took part
      in the study. From the results it appeared that social support, growth
      opportunities and work pressure are related to work satisfaction, work motivation
      and health complaints. The individual variables need for autonomy and coping
      strategies showed main effects as well as moderating- (buffer-) effects. On the
      basis of the findings practical consequences for the management of personnel and
      work have been formulated.

PMID- 9516815
TI  - [Ranking and weighing of quality criteria. An application of criteria concerning
      nursing follow-up care of COPD patients].
AB  - The primary question in this survey was: Is it possible for a panel of experts,
      by means of existing measurement scales, to weigh and rank criteria in order to
      get a more refined judgement of quality. For this purpose 134 criteria were
      presented to a panel of experts using the Delphi-method. In two Delphi-rounds the
      panel selected 28 most important and 18 least important criteria by means of the
      VAS and the Coombsscale. This resulted in a selection of 34% of the original
      number of 134 criteria. The results proved it to be possible, to rank and weigh
      criteria by means of the VAS and Coombsscale in a Delphi-survey. If it is desired
      that a numerical value be attributed to criteria which differ little on a
      notional continuum, the Coombsscale appears to be most suitable. The VAS is not
      adequate in reaching 70% consensus in regarding least important criteria in a
      group of existing criteria.

PMID- 9516816
TI  - [Caregiving and/or nursing care?].

PMID- 9516817
TI  - [The concept scope of nursing].

PMID- 9516818
TI  - [Early recognition of prodromal symptoms in patients with schizophrenia. The
      exploration of an attention field for nurses].
AB  - The present article explores the significance of prodromal symptoms in the
      prevention of psychotic relapse in schizophrenic patients. Prodromal symptoms are
      changes in patient's subjective perception and observable behavior which may
      signal the onset of psychosis. The article first describes the process of
      psychotic decompensation and continues with the description of the most common
      prodromes, the situation in which they may be observed and who may observe them.
      The discussion also touches on the predictive value of prodromal symptoms, i.e.
      their ability to predict an impending psychosis correctly. Finally, the article
      discusses the various interventions available to nurses, focusing in particular
      on two aspects. The first aspect is the drafting of observation plans aimed at
      recognizing prodromal symptoms at an early stage. The second describes how such
      plans can be linked to the education and information provided to patients and to
      others in the patient's environment.

PMID- 9516819
TI  - [The Braden Scale--validity and reliability of a measuring tool for decubitus
      risk factors].
AB  - In this article the results of explorative research into the validity and
      reliability of a Dutch version of the Bradenscale are described. The Bradenscale
      is a risk assessment tool for measuring the risk of developing pressure sores.
      With a prospective longitudinal design the Bradenscale has been investigated in a
      hospital and a community setting in Belgium and the Netherlands. Results of the
      research in hospital indicate a fair to moderate agreement with respect to
      interraterreliability and a reasonable amount of predictive validity. In the
      community care setting interraterreliability indicates slight to fair agreement
      while predictive validity could not be established due to several reasons.
      Further research into the Bradenscale is recommended considering the limited
      research population in both studies and the results in community care.

PMID- 9516820
TI  - [Towards congruence in nursing information provision in The Netherlands].
AB  - Few reliable data are available about nursing care in the Netherlands, whereas
      pressure from society to support the contributions of the discipline of nursing
      to health care delivery increases. This paper presents an information model to
      support analytical access to nursing labour and services. This model, the nursing
      information reference model (Dutch acronym 'VIRM') focuses on the structure to
      achieve congruence between data from the primary process of nursing care and data
      derived from that process for clinical practice, management, research, and policy
      purposes. The model is based on the 'collect-once/use-often' principle of data
      collection and management, which emphasizes single collection and registration
      through the patient record for multiple subsequent uses and purposes. In this
      paper core elements of the VIRM are being discussed. Determination of data from
      the primary process of nursing care to be provided for certain aims is currently
      being conducted by the Dutch Nursing Minimum Data Set (VMDNS) initiative. The
      article at issue should be understood as a starting point in the discussion about
      the development of a Nursing Minimum Data Set in the Netherlands.

PMID- 9516821
TI  - [Nursing diagnosis--questions which remained unanswered].
AB  - This article concerns one of the research questions in the project on
      'Terminology in Dutch Nursing: Towards clarification, classification and
      standardization of nursing concepts', i.c. related to the conceptual definition
      of nursing diagnosis. On the one hand those parts are reported on which agreement
      was reached, by means of literature research and analysis of documents,
      interviews with key-informants and group discussions and through a Delphi
      research. On the other hand, those aspects of the proposed conceptual definition
      are elucidated on which discussions seem not to be closed yet or that are missing
      in the definition for lack of agreement. These discussion points are explored,
      thus following one of the recommendations of the research project on 'Terminology
      in Dutch Nursing', namely for further refinement of the proposed working
      definition of the concept nursing diagnosis. Finally some suggestions are made to
      realize this solicited refinement.

PMID- 9516822
TI  - [Methodological quality of qualitative studies--potential measures].
AB  - Methodological quality of scientific research is argumentative persuasiveness of
      the conclusions of the research. Aspects of methodological quality are:
      methodological objectivity (including reliability, validity, subjectivity and
      intersubjectivity), generalizability, and, regarding action-oriented research,
      action-rationality. Values, which are only partly of a methodological nature,
      are: transferability, utilization-value, implementary value and participatory
      value. Concerning each of these norms and values a variety of measures to promote
      methodological quality in qualitative inquiry are discussed.

PMID- 9516823
TI  - Evidence that the MYCN oncogene regulates MRP gene expression in neuroblastoma.
AB  - We have recently shown that expression of the multidrug resistance-associated
      protein (MRP) gene is a powerful prognostic indicator in childhood neuroblastoma
      and have suggested that the MYCN oncogene may regulate MRP gene expression. To
      address this hypothesis, we have examined the relationship between MYCN and MRP
      gene expression in neuroblastoma tumours and cell lines. MYCN and MRP gene
      expression were highly correlated in 60 primary untreated tumours both with (P =
      0.01) and without MYCN gene amplification (P < 0.0001). Like MRP, high MYCN gene
      expression was significantly associated with reduced survival, both in the
      overall study population and in older children without MYCN gene amplification
      (relative hazards = 13.33 and 19.61, respectively). Inhibition of MYCN, through
      the introduction of MYCN antisense RNA constructs into human neuroblastoma cells
      in vitro, resulted in decreased MRP gene expression, determined both by RNA-PCR
      and Western analysis. The data are consistent with MYCN influencing neuroblastoma
      outcome by regulating MRP gene expression.

PMID- 9516824
TI  - Loss of chromosome 1p may have a prognostic value in localised neuroblastoma:
      results of the French NBL 90 Study. Neuroblastoma Study Group of the Societe
      Francaise d'Oncologie Pediatrique (SFOP).
AB  - Between March 1990 and December 1994, 316 consecutive children with localised
      neuroblastoma were registered in the French NBL 90 study. In addition to the
      assessment of a new chemotherapy regimen in unresectable neuroblastoma, we
      evaluated the prognostic significance of MYCN amplification and loss of the short
      arm of chromosome 1 (LOH1p). MYCN was found in 22/225 children (10%) and
      associated with unfavourable clinical features such as age at diagnosis > 1 year
      and large and unresectable tumours. LOH1p was observed in 9/91 patients (10%), of
      whom some had favourable prognostic factors such as age at diagnosis < 1 year (n
      = 4), INSS stage 1 or 2 (n = 3) and no MYCN amplification (n = 4). Overall
      survival (OS) and event-free survival (EFS) were, respectively, 56% and 22%
      (median follow-up: 36 months) for children with LOH1p compared with 97% and 94%
      for those without (log-rank = 10(-8)). All except 1 of the 5 children with MYCN
      amplification and LOH1p relapsed and ultimately died of the disease. Among the 4
      with LOH1p and no MYCN amplification, recurrence occurred in 3 (2 local, 1
      metastatic), all alive in second remission after salvage therapy (12-19 months
      after the relapse). In multivariate analysis, LOH1p was the strongest prognostic
      indicator for subsequent relapse. LOH1p appears more discriminant than MYCN
      amplification for predicting the risk of recurrence in children with localised
      neuroblastoma. However, its analysis was possible in only 30% of our patients and
      its final impact on survival should be confirmed in larger, prospective studies
      in order to stratify subsequent treatment.

PMID- 9516825
TI  - Molecular genetic analysis of familial neuroblastoma.
AB  - Neuroblastoma has several clinical and molecular genetic parallels with the other
      paediatric embryonal tumours, such as retinoblastoma, including a hereditary form
      of the disease. We hypothesised that neuroblastoma susceptibility is due to
      germline mutations in a tumour suppressor gene and that this predisposition gene
      may be involved in sporadic neuroblastoma tumorigenesis as well. We therefore
      aimed to localise the familial neuroblastoma predisposition gene by linkage
      analysis in neuroblastoma kindreds. Eighteen families segregating for
      neuroblastoma were ascertained for candidate locus linkage analysis. Although
      many of the 49 affected individuals in these families were diagnosed as infants
      with multifocal primary tumours, there was marked clinical heterogeneity. We
      originally hypothesised that familial neuroblastoma predisposition would map to
      the telomeric portion of chromosome band 1p36, a genomic region likely to contain
      a sporadic neuroblastoma suppressor gene. However, neuroblastoma predisposition
      did not map to any of eight polymorphic markers spanning 1p36.2-.3 in three large
      kindreds. In addition, there was strong evidence against linkage to two
      Hirschsprung disease susceptibility genes (RET and EDNRB), a condition that can
      cosegregate with neuroblastoma as in one of the kindreds tested here. We conclude
      that the neuroblastoma susceptibility gene is distinct from the 1p36
      neuroblastoma suppressor and two of the currently identified Hirschsprung disease
      susceptibility genes.

PMID- 9516826
TI  - Telomerase expression in primary neuroblastomas.
AB  - Maintenance of chromosomal telomeres is necessary for continued cell growth, and
      this is carried out in germline tissues by telomerase. In contrast to most
      somatic tissues, many tumours have telomerase activity. The RNA component of
      human telomerase (hTR) was measured by Northern analyses of 150 primary untreated
      neuroblastomas and compared with clinical stage at diagnosis. hTR expression > 33
      (relative to cell line control = 100) was seen in 41% of all tumours and the
      frequency of hTR > 33 increased with stage of disease. Expression of hTR may be
      involved in progression of neuroblastoma.

PMID- 9516827
TI  - Telomerase activity in neuroblastoma: is it a prognostic indicator of clinical
      behaviour?
AB  - Neuroblastomas show remarkable biological heterogeneity, resulting in favourable
      prognosis or unfavourable prognosis due to aggressive growth despite multimodal
      therapy. Recently, we proposed that aggressive tumours express telomerase at a
      high level while the favourable tumours lack or have low telomerase expression.
      To evaluate the correlation between telomerase activity and other biological
      characteristics reported as prognostic markers (MYCN gene amplification, loss of
      heterogeneity (LOH) in the short arm of chromosome 1, trk-A expression, Ha-ras
      p21 expression, and DNA ploidy), we investigated these biological features in 105
      untreated neuroblastomas. In these cases, 23 showed high telomerase activity, 78
      showed low activity, and telomerase activity was undetectable in 4 cases. Most
      tumours with genetic alterations (MYCN amplification or 1p32 LOH) showed high
      telomerase activity. Most tumours with low or undetectable activity were
      aneuploid, and showed trk-A and Ha-ras expression. Three of the four tumours with
      undetectable telomerase activity regressed. In 2 of the tumours with low
      telomerase activity, the residual tumours maturated and showed repression of
      telomerase activity. Thus, the level of telomerase activity correlated with other
      genetic alterations and/or gene expression and may be a useful prognostic
      indicator in neuroblastoma.

PMID- 9516828
TI  - Expression of a 260 kDa neuroblastoma surface antigen, the target of cytotoxic
      natural human IgM: correlation to MYCN amplification and effects of retinoic
      acid.
AB  - Human neuroblastoma cells contain a 260 kDa surface-associated antigen (NB-p260)
      that is recognised by natural cytotoxic IgM antibodies. In this study we
      demonstrate that NB-p260 is expressed in vivo in a neuroblastoma tumour specimen
      but not in normal human tissues of neuronal origin. Since MYCN amplification is a
      clinical marker of neuroblastoma disease progression, we analysed the expression
      of NB-p260 in human neuroblastoma cell lines with different MYCN amplification
      status. However, both amplified and non-amplified neuroblastoma cell lines
      exhibited comparable NB-p260 expression. Treatment of neuroblastoma cells with
      the differentiation-inducing agent retinoic acid (RA) also had no effect on the
      expression of NB-p260. Collectively, the data suggest that expression of NB-p260
      on human neuroblastoma cells is independent of malignancy and differentiation
      status of neuroblastoma.

PMID- 9516829
TI  - Mechanisms of in vivo anti-neuroblastoma activity of human natural IgM.
AB  - Normal human sera of healthy adults contain natural IgM antibodies which are
      cytotoxic for human neuroblastoma cells. In this study, we evaluated the anti
      neuroblastoma activity of these natural IgM antibodies in nude rats bearing solid
      human neuroblastoma tumours. A single intravenous (i.v.) injection of purified
      cytotoxic IgM led to uptake of IgM in the tumours with massive perivascular
      complement activation and accumulation of neutrophil granulocytes after 24 h.
      Five consecutive i.v. injections of purified cytotoxic IgM into neuroblastoma
      bearing animals resulted in complete growth arrest of even large established
      solid tumours which lasted for several weeks after discontinuation of the
      injections, whereas tumours of control animals continued to grow exponentially
      during the observation period. These studies suggest that natural anti
      neuroblastoma IgM may have a potential as a novel therapeutic modality in the
      treatment of human neuroblastoma.

PMID- 9516830
TI  - Restriction fragment length polymorphism analysis reveals different allele
      frequency and a linkage disequilibrium at locus D1S94 in neuroblastoma patients.
AB  - Deletion of chromosome 1p and MYCN amplification have been reported as frequent
      abnormalities in human neuroblastoma. We studied loss of heterozygosity (LOH) in
      50 (48 informative) Italian neuroblastoma patients by restriction fragment length
      polymorphisms (RFLPs) analysis using anonymous and hypervariable region (HVR)
      sequences. Twelve cases (25%) showed LOH at one or more loci. Locus D1S94 was the
      most frequently involved in LOH events (8/12) of deleted cases (66.6%). MYCN
      amplification was observed in 20% of patients which showed a significantly lower
      event-free survival probability (EFSp) (P = 0.004). We also studied the allelic
      distribution in the constitutional DNA of neuroblastoma patients (n = 44) and a
      matched group of healthy Italian subjects (n = 79) for loci D1S112 and D1S94. A
      significantly (P = 0.01) different allele frequency was detected for the two
      groups at locus D1S94, but not at D1S112. Moreover, the neuroblastoma population
      did not confirm the Hardy-Weinberg expectations at the former locus. This
      observation suggests the existence of an allelotype associated with neuroblastoma
      susceptibility.

PMID- 9516831
TI  - Loss of heterozygosity for chromosome 1p in familial neuroblastoma.
AB  - Loss of heterozygosity (LOH) and deletion of chromosome 1p are very often found
      in sporadic neuroblastoma. Nevertheless, very few data are available concerning
      1p LOH in familial neuroblastoma. Families with recurrent neuroblastoma are rare
      and analysis of chromosome 1p in these families might give useful information for
      identifying the putative neuroblastoma suppressor gene. We used combined
      cytogenetic and molecular techniques to study 1p LOH in two neuroblastoma
      families. Family M has 2 out of 3 children with neuroblastoma and family C has 2
      children, 1 of whom has neuroblastoma and type 1 neurofibromatosis (NF1). All
      patients of both families showed tumour cells with chromosome 1p deletion
      (1pdel), but only the patient from family C also had MYCN gene amplification. In
      all cases the deleted chromosome 1 was of maternal origin.

PMID- 9516832
TI  - Molecular analysis of the region of distal 1p commonly deleted in neuroblastoma.
AB  - Cellular, cytogenetic, and molecular evidence indicates that chromosome band 1p36
      is often deleted in neuroblastoma cell lines and tumours, suggesting the presence
      of one or more tumour suppressor genes in this region. We used a multifaceted
      approach to analyse the commonly deleted region, 28 distal 1p-specific
      polymorphic loci were used to detect loss of heterozygosity (LOH) in a panel of
      primary neuroblastoma tumours. Thirty-two of 122 tumours (26%) demonstrated LOH
      at three or more loci. In addition, a patient with a constitutional deletion of
      1p36.2-.3 and two neuroblastoma cell lines with 1p36 abnormalities were
      characterised by FISH. When combined with the LOH data, a single consensus region
      of deletion was defined proximally by PLOD and distally by D1S80, a region
      spanning approximately five megabases. Several proposed candidate tumour
      suppressor genes, including ID3, CDC2L1, DAN, PAX7, E2F2, TNFR2 and TCEB3, map
      outside of this region; however, the transcription factor HKR3 cannot be
      excluded. LOH for 1p is correlated with adverse clinical and biological features
      and a poor prognosis, but 1p LOH is not an independent predictor of overall
      survival. To identify additional candidate genes, an integrated physical map of
      1p35-36 is being constructed. The current map includes 445 polymerase chain
      reaction (PCR)-formatted markers and 608 YACs. This map will help identify region
      specific transcripts by direct selection and sequencing.

PMID- 9516833
TI  - Alterations of the tumour suppressor gene DCC in neuroblastoma.
AB  - The deleted in colorectal carcinoma (DCC) gene, a candidate tumour suppressor,
      might be inactivated in a number of human cancers. In order to evaluate the
      possible role of DCC alterations in the pathogenesis of neuroblastoma, we
      examined 25 neuroblastoma cell lines and 16 primary tumours, including 6 samples
      with loss of heterozygosity (LOH) at the DCC locus for DCC mRNA expression, by
      using the reverse transcriptase-polymerase chain reaction (RT-PCR) technique. The
      level of DCC expression was significantly reduced or undetectable in 12 of 25
      (48%) cell lines and 7 of 16 (44%) primary tumours, suggesting that inactivation
      of the DCC gene is involved in the development of neuroblastoma. Three of the 6
      tumours with LOH at the DCC locus revealed reduced DCC mRNA expression,
      indicating that LOH at the DCC locus might have affected the levels of DCC mRNA.
      We also screened for mutations in 4 exons of the DCC gene in 12 cell lines by
      using PCR-single strand conformation polymorphism (PCR-SSCP) analysis. Point
      mutations were not found except a polymorphic change at codon 201. The mechanism
      for inactivation of the DCC gene will be further investigated.

PMID- 9516834
TI  - Representational difference analysis and loss of heterozygosity studies detect 3p
      deletions in neuroblastoma.
AB  - In an attempt to identify genes involved in neuroblastoma, we scanned
      neuroblastoma tumour DNAs for homozygous deletions by representational difference
      analysis (RDA). The RDA produced several difference products, nine of which
      represented hemizygous deletions located on chromosome 1 or 3. In order to detect
      deletions, a genomewide loss of heterozygosity (LOH) screening with polymorphic
      markers was performed. Allelic losses on a number of different chromosomes were
      detected, mainly in favourable neuroblastomas (stage 1, 2 and 4S). The most
      frequently deleted region, apart from 1p, was chromosomal region 3p. A more
      detailed study was made in this region, which showed that 9 out of 58 (16%)
      tested neuroblastoma tumours showed allelic loss in the same region on chromosome
      3p, i.e. 3pter-14.2. Thus, both RDA and LOH studies showed chromosome region 3p
      as being frequently involved in deletions and/or rearrangements in neuroblastoma
      tumours. Therefore, it is possible that one or more of the 3p genes implicated in
      the development of other cancers also play a role in neuroblastoma development
      and/or progression.

PMID- 9516835
TI  - Loss of heterozygosity in neuroblastomas--an overview.
AB  - Although previous studies have demonstrated a relatively high incidence of loss
      of heterozygosity (LOH) on chromosomes 1p, 11q and 14q in neuroblastoma, it is
      unclear whether LOH occurs specifically on these chromosomes or not. It might be
      due to the lack of allelotyping of neuroblastoma. When we assessed all 22
      autosomes and chromosome X for LOH in 81 cases of neuroblastoma using 43
      polymorphic DNA markers, a high incidence of LOH (> 30%) was observed on three
      chromosomal arms, 2q (30%), 9p (36%) and 18q (31%). Moreover, 9p LOH in the
      tumours showed statistically significant association with advanced stage of the
      disease and poor prognosis. Therefore, tumour suppressor genes on chromosomes 2q,
      9p and 18q could be involved in the genesis and/or progression of neuroblastoma.
      Particularly, the gene on chromosome 9p may be associated with progression of
      neuroblastoma.

PMID- 9516836
TI  - Analysis of 1;17 translocation breakpoints in neuroblastoma: implications for
      mapping of neuroblastoma genes.
AB  - Deletions and translocations resulting in loss of distal 1p-material are known to
      occur frequently in advanced neuroblastomas. Fluorescence in situ hybridisation
      (FISH) showed that 17q was most frequently involved in chromosome 1p
      translocations. A review of the literature shows that 10 of 27 cell lines carry
      1;17 translocations. Similar translocations were also observed in primary
      tumours. Together with the occurrence of a constitutional 1;17 translocation in a
      neuroblastoma patient, these observations suggest a particular role for these
      chromosome re-arrangements in the development of neuroblastoma. Apart from the
      loss of distal 1p-material, these translocations invariably lead to extra copies
      of 17q. This also suggested a possible role for genes on 17q in neuroblastoma
      tumorigenesis. Further support for this hypothesis comes from the observation
      that in those cell lines without 1;17 translocations, other chromosome 17q
      translocations were present. These too lead to extra chromosome 17q material.
      Molecular analysis of 1;17 translocation breakpoints revealed breakpoint
      heterogeneity both on 1p and 17q, which suggests the involvement of more than 2
      single genes on 1p and 17q. The localisation of the different 1p-breakpoints
      occurring in 1;17 translocations in neuroblastoma are discussed with respect to
      the recently identified candidate tumor suppressor regions and genes on 1p. In
      this study, we focused on the molecular analysis of the 17q breakpoints in 1;17
      translocations. Detailed physical mapping of the constitutional 17q breakpoint
      allowed for the construction of a YAC contig covering the breakpoint.
      Furthermore, a refined position was determined for a number of 17q breakpoints of
      1;17 translocations found in neuroblastoma cell lines. The most distal 17q
      breakpoint was identified in cell line UHG-NP and mapped telomeric to cosmid
      cCI17-1049 (17q21). This suggests that genes involved in a dosage-dependent
      manner in the development of neuroblastoma map in the distal segment 17q22-qter.
      Future studies aim at the molecular cloning of 1;17 translocation breakpoints and
      at deciphering the mechanisms leading to 1;17 translocations and possibly to the
      identification of neuroblastoma genes at or in the vicinity of these breakpoints.

PMID- 9516837
TI  - Sensitive and reliable detection of genomic imbalances in human neuroblastomas
      using comparative genomic hybridisation analysis.
AB  - Deletions of the short arm of chromosome 1, extra copies of chromosome 17q and
      MYCN amplification are the most frequently encountered genetic changes in
      neuroblastomas. Standard techniques for detection of one or more of these genetic
      changes are karyotyping, FISH analysis and LOH analysis by Southern blot or PCR.
      Each of these techniques has its own particular limitations. More recently,
      comparative genomic hybridisation (CGH) was introduced for detection of genomic
      imbalances including deletions, duplications and gene amplification. We evaluated
      the sensitivity and reliability of CGH for detection of the most frequently
      encountered genetic changes in neuroblastoma. For this purpose a panel of well
      characterised neuroblastoma cell lines as well as a series of 11 primary
      neuroblastomas was analysed. Our results show that CGH is a valuable tool for the
      genetic characterisation of neuroblastomas, both for the detection of frequently
      occurring genomic imbalances and for the identification of previously unnoticed
      genetic changes.

PMID- 9516838
TI  - Prognostic relevance of genetic alterations in the p32 region of chromosome 1 in
      neuroblastoma.
AB  - Thirty-six neuroblastomas were analysed for chromosome 1p alterations and their
      prognostic relevance. In 72% (26/36) of the patients, 1p alterations were
      identified in the tumours using 24 polymorphic loci ranging 1p22-1p36.3. LOH was
      identified in 25 children, and in 10 additional allelic imbalance was identified.
      In 1 child allelic imbalance was the sole alteration. Imbalance was termed as
      gain in intensity of one allele with or without reduction of the second allele (<
      50%). The imbalance was identified in adjacent regions to the LOH. Two distinct
      regions of LOH were identified: 1p36.1-p36.3 and 1p31-p32. The common imbalance
      regions overlapped the common LOH regions. The children with LOH and imbalance
      had improved survival (100%) compared to the children with LOH only (26%) after
      48 months of follow-up. The imbalance had an advantageous effect that is
      reflected by the improved outcome in children with other unfavourable clinical
      features.

PMID- 9516839
TI  - A product of DAN, a novel candidate tumour suppressor gene, is secreted into
      culture medium and suppresses DNA synthesis.
AB  - Our previous studies have shown that the DAN gene product possesses an ability to
      revert phenotypes of transformed rat fibroblasts and represents a candidate
      tumour suppressor gene for neuroblastoma. In the present study, characterisation
      of DAN was carried out using rat fibroblast 3Y1 cells and their DAN-overexpressor
      counterparts (S-9). The N-terminal region of DAN (amino acids 1-24) was highly
      hydrophobic and DAN protein was found to be secreted into the culture medium.
      When DAN was treated with PNGase F, a enzyme that cleaves most N-linked
      carbohydrate residues, the mobility of both cytoplasmic and secreted DAN was
      increased in SDS-polyacrylamide gel electrophoresis, suggesting DAN is N
      glycosylated, irrespective of its localisation. When partially purified, DAN was
      able, when added to the culture, to suppress DNA synthesis of Rous sarcoma virus
      transformed 3Y1 cells, which lack the expression of DAN.

PMID- 9516840
TI  - Human Kruppel-related 3 (HKR3): a candidate for the 1p36 neuroblastoma tumour
      suppressor gene?
AB  - Human Kruppel-related 3 (HKR3) is a zinc finger gene that maps within chromosome
      subbands 1p36.2-.3, a region postulated to contain a tumour suppressor gene
      associated with advanced neuroblastomas. Genomic clones of HKR3 were isolated
      from a P1 library and physically mapped to within 40 kb of D1S214 at 1p36.3. The
      gene is ubiquitously expressed in human tissues, but especially high levels are
      present in human fetal and adult nervous tissues. Hemizygous deletion of HKR3 in
      a lymphoblastoid cell line derived from a neuroblastoma patient with a
      constitutional 1p36 interstitial deletion and in the neuroblastoma cell line SK-N
      AS, which also has a small interstitial 1p36 deletion, has been observed. Allelic
      loss at D1S214 in 15/15 informative primary neuroblastoma specimens with 1p36
      deletions has also been observed. In a panel of 16 neuroblastoma cell lines, no
      gross genomic DNA rearrangements were noted, the gene was always expressed
      (albeit at variable levels) and there was no evidence for truncating mutations.
      Furthermore, there were no mutations detected in the zinc finger coding region in
      four neuroblastoma cell lines with 1p deletions analysed by direct sequence
      analysis. We conclude that HKR3 is a novel zinc finger gene that maps to a region
      of the genome commonly rearranged or deleted in neuroblastoma and other human
      cancers.

PMID- 9516841
TI  - Delimitation of a critical tumour suppressor region at distal 1p in neuroblastoma
      tumours.
AB  - We analysed DNA from 68 neuroblastoma tumours for loss of heterozygosity (LOH) on
      the distal chromosome 1p (1p-LOH) using PCR-based DNA polymorphisms. Fifteen
      tumours (22%) displayed 1p-LOH. The shortest region of overlap (SRO) for the
      deletions was defined proximally by marker D1S244 and distally by marker D1S80.
      The CDC2L1 locus, located on chromosome 1p36, has been put forward as a
      neuroblastoma tumour suppressor. We analysed coding regions of the CDC2L1 gene in
      a subset of aggressive neuroblastoma tumours with known allelic loss for
      different 1p-markers. Single-stranded conformation polymorphism, heteroduplex and
      sequencing analysis of tumour DNA did not reveal any significant changes in the
      coding region. Using a DNA sequence polymorphism, we showed, in a primary tumour
      with an interstitial allelic deletion, that this tumour had both alleles of the
      CDC2L1 locus retained in the tumour. Thus, we showed that the neuroblastoma
      tumour suppressor critical region on 1p in our material is defined by loci D1S244
      and D1S80 and that the CDC2L1 locus is distal to the critical region.

PMID- 9516842
TI  - Drug resistance in human neuroblastoma cell lines correlates with clinical
      therapy.
AB  - To determine if neuroblastoma acquires a sustained drug-resistant phenotype from
      patient exposure to therapy, we studied neuroblastoma cell lines established at
      different points of therapy: at diagnosis prior to therapy, at progressive
      disease after induction therapy and at relapse after intensive chemoradiotherapy
      and bone marrow transplantation (post-BMT). Melphalan, cisplatin, carboplatin,
      doxorubicin, and etoposide cytotoxicities were determined by DIMSCAN assay. Drug
      resistance progressively increased with therapy and 3/5 post-BMT lines showed
      high resistance to most drugs. IC 90s 37, 78, 719 and 256 times higher than
      clinically achievable drug levels were obtained in post-BMT cell lines for
      melphalan, cisplatin, doxorubicin and etoposide, respectively. Resistance
      correlated with the therapies patients received: considerable etoposide and
      doxorubicin resistance (> 1000-fold resistance) was seen in cell lines obtained
      from patients treated with these drugs. These cell lines indicate that
      neuroblastoma acquires resistance to cytotoxic drugs that is probably due to
      stable genetic alterations occurring during therapy.

PMID- 9516843
TI  - Betulinic acid induces apoptosis in human neuroblastoma cell lines.
AB  - Neuroblastoma has long been recognized to show spontaneous regression during
      fetal development and in the majority of stage 4s infants < 1 year of age with
      disseminated disease. Stage 4s disease regresses with no chemotherapy in 50% of
      the patients. The mechanism by which this occurs is not understood but may be
      programmed cell death or apoptosis. Betulinic acid (BA) has been reported to
      induce apoptosis in human melanoma with in vitro and in vivo model systems.
      Melanoma, like neuroblastoma, is derived from the neural crest cell. We
      hypothesised that neuroblastoma cells have the machinery for programmed cell
      death and that apoptosis could be induced by betulinic acid. Nine human
      neuroblastoma cell lines were treated in vitro with BA at concentrations of 0-20
      micrograms/ml for 0-6 days. Profound morphological changes were noted within 3
      days. Cells withdrew their axonic-like extensions, became non-adherent and
      condensed into irregular dense spheroids typical of apoptotic cell death (ED50 =
      14-17 micrograms/ml). DNA fragmentation analysis showed ladder formation in the
      100-1200 bp region in 3/3 neuroblastoma cell lines treated with BA for 24-72 h.
      Thus, apparently BA does induce AP in neuroblastoma in vitro. This model will be
      utilised to investigate the role of apoptosis-related genes in neuroblastoma
      proliferation and to determine the therapeutic efficacy of BA in neuroblastoma in
      vivo.

PMID- 9516844
TI  - DNA-topoisomerase I, a new target for the treatment of neuroblastoma.
AB  - DNA-topoisomerase I is the nuclear target of new anticancer drugs, namely
      camptothecin and its derivatives. In order to establish the rational basis for
      their clinical development in paediatric oncology, the antitumour activity of
      irinotecan (CPT-11) and topotecan, two camptothecin water-soluble derivatives,
      was studied in nude mice bearing neuroblastoma xenografts. The panel was composed
      of 4 previously established subcutaneous xenograft lines (IGR-N835, IGR-N91, IGR
      NB3, IGR-NB8) that exhibited the common biological markers of poor prognosis in
      children (MYCN amplification, 1p deletion, paradiploidy and/or MDR1
      overexpression). Irinotecan and topotecan were administered i.v. or i.p. over 5
      consecutive days in animals bearing tumours. Irinotecan (40 mg/kg/day) induced 20
      100% complete regressions with tumour growth delays ranging from 20 to 46 days.
      Two out of 10 IGR-N91 bearing animals were tumour free more than 120 days after
      treatment with the top dose (50 mg/kg/day). Topotecan (2.7 mg/kg/day) induced 0
      67% complete regressions with tumour growth delays ranging from 23 to 50 days.
      One out of 8 IGR-NB3 bearing mice was tumour free at the end of the experiment.
      The antitumour activity of both drugs was clearly sustained at a lower dose
      level. Topoisomerase I activity was assayed in 15 neuroblastomas, 3
      ganglioneuroblastomas and 2 normal adrenal glands, using a DNA relaxation assay.
      Topoisomerase I activity ranged from 69 to 1304 arbitrary units/mg of protein,
      and was significantly higher in immature neuroblastomas than in
      ganglioneuroblastomas and adrenal glands. In conclusion, irinotecan and topotecan
      are active against neuroblastoma xenografts. Their target is expressed in
      patients' tumour samples. Clinical development of topoisomerase I inhibitors in
      children with neuroblastoma is warranted.

PMID- 9516845
TI  - Buthionine sulphoximine alone and in combination with melphalan (L-PAM) is highly
      cytotoxic for human neuroblastoma cell lines.
AB  - Buthionine sulphoximine (BSO) selectively inhibits glutathione (GSH) synthesis
      and may enhance the antineuroblastoma activity of melphalan (L-PAM). We
      determined the cytotoxicity of BSO (dose range 0-1000 microM) alone and in
      combination with L-PAM (dose range 0-0 microM) in a panel of 18 human
      neuroblastoma cell lines. BSO alone was highly cytotoxic with 16/18 neuroblastoma
      cell lines having IC90 values (range 2.1- > 1000 microM) below the clinically
      achievable steady-state plasma level of 500 microM BSO. Maximal cell killing
      correlated with GSH levels decreased to less than 10% baseline, and was partially
      reversed by the addition of exogenous anti-oxidants (GSH, vitamin E and
      ascorbate). Fluorocytometric analysis of DNA fragments by the Tunnel method
      detected 92% of a BSO sensitive cell line in apoptosis after a 48 h exposure to
      500 microM BSO. The combination of L-PAM and BSO synergistically enhanced the
      cell killing of L-PAM alone by > 1-3 logs (combination index < 1). We conclude
      that BSO has significant single-agent cytotoxicity against neuroblastoma and
      enhances cell killing when combined with L-PAM.

PMID- 9516846
TI  - Angiostatic treatment of neuroblastoma.
AB  - The growth of solid tumours has been shown to be dependent on new blood vessel
      formation, i.e. angiogenesis. Several steps in the metastatic process have also
      been found to be angiogenesis dependent. The mediators of tumour angiogenesis are
      now being elucidated, and angiostatic agents have been developed. Some of these
      agents are currently undergoing clinical trials. In addition to inhibition of
      angiogenesis, two other clinical applications of angiogenetic research in tumour
      diseases are monitoring of disease activity by analyses of circulating angiogenic
      peptides and prediction of a poor outcome by tumour microvascular counts.
      Neuroblastomas grow quickly, are highly vascularised and metastasise early and
      hence inhibition of angiogenesis--angiostatic therapy--may be indicated in this
      disease. The effects of treatment with the angiostatic agent TNP-470 in an
      experimental model results in a significant reduction of the tumour growth rate,
      reduced microvascular counts and a reduced fraction of viable tumour cells
      compared to controls. TNP-470 as single therapy has an objective tumoristatic
      effect in our neuroblastoma model. Angiostatic treatment of neuroblastoma is a
      new and theoretically promising treatment modality that merits clinical
      investigations. The feasibility of assessing disease activity by repeated
      determinations of the levels of circulating angiogenic peptides should also be
      determined, as well as the use of microvascular counts to predict a poor outcome.

PMID- 9516847
TI  - Detection of neuroblastoma cells in CD34+ selected peripheral stem cells using a
      combination of tyrosine hydroxylase nested RT-PCR and anti-ganglioside GD2
      immunocytochemistry.
AB  - A sensitive assay was developed for the detection of neuroblastoma cell
      contamination in CD34+ selected and unseparated peripheral blood stem cells
      (PBSC) used for autologous transplantation in stage 4 neuroblastoma patients.
      Specifically, we established a non-radioactive nested cDNA-PCR (nPCR) for
      detection of tyrosine hydroxylase (TH) gene expression combined with anti
      disialoganglioside GD2 immunocytochemistry with the murine monoclonal antibody
      (MAb) 14G2a. Sensitivities of TH nPCR determined with a number of neuroblastoma
      cell lines and PBSCs correlated to cell line dependent basal TH gene expression
      levels and ranged from 1:10(4) to 1:10(6). The sensitivity obtained by
      immunocytochemistry was 1:10(5). We observed the highest PBSC contamination rate
      of 47% (18/38) among 38 PBSC specimens exclusively obtained from stage 4
      neuroblastoma patients by using TH nPCR and GD2 immunocytochemistry in
      combination. Furthermore, a clinically applied purging method, CD34+ selection by
      immunoabsorption (CD34+ purity 42.4%), was used on 16 PBSCs. 10/16 (63%)
      preparations were contaminated prior to CD34+ selection and 56% (9/16) remained
      contaminated. A significant reduction of neuroblastoma cell contamination by
      CD34+ selection was not detectable, but the absolute amount of re-infused tumour
      cells was decreased due to 100-fold smaller cell counts of CD34+ selected grafts
      used for transplantation. 22 PBSC preparations were used for transplantation. A
      Kaplan-Meier analysis showed an event-free survival probability of 0.56 +/- 0.22
      (n = 9) in the group with contaminated PBSCs versus 0.88 +/- 0.12 (n = 8) with no
      detectable neuroblastoma-cell contamination. Our data suggest that the combined
      use of TH nPCR and GD2 immunocytochemistry is optimal to detect contamination and
      monitor purging strategies.

PMID- 9516848
TI  - The prognostic value of MDR1 gene expression in primary untreated neuroblastoma.
AB  - The contribution of MDR1 gene expression to the biology of childhood
      neuroblastoma is unclear. To clarify the role of MDR1 in this malignancy, we
      examined the relationship between MDR1 expression and patient outcome in subsets
      of 60 primary untreated neuroblastomas for which MYCN gene copy number and
      expression of the multidrug resistance-associated-protein (MRP) gene had been
      previously characterised. In contrast to MRP gene expression, MDR1 expression was
      lower in tumours with MYCN gene amplification compared with those without
      amplification. Strong correlations between MDR1 and MRP gene expression, and
      between MDR1 and MYCN gene expression, were observed in tumours lacking MYCN gene
      amplification (P < 0.0005). In these single-copy tumours, very high MDR1 gene
      expression was significantly associated with poor outcome (P < 0.05). Very high
      MDR1 expression was also strongly predictive of poor outcome in older children (P
      < 0.0001), but not in infants. These findings suggest a clinical role for the
      MDR1 gene in specific subgroups of primary neuroblastoma.

PMID- 9516849
TI  - Analysis of candidate gene co-amplification with MYCN in neuroblastoma.
AB  - Previous studies have revealed that the MYCN gene spans approximately 7kb, while
      the amplicon has been estimated to be 100 kb to 1 Mb long [1-3]. This implies
      that several other genes may be present on the MYCN amplicon. Such co-amplified
      genes could contribute to the malignant phenotype and might provide an
      explanation for why not all patients with MYCN amplification have a poor outcome.
      We investigated 7 neuroblastoma cell lines and 167 primary tumours for the co
      amplification of candidate genes known to be present near the MYCN locus:
      ornithine decarboxylase, ribonucleotide reductase, syndecan-1 and a DEAD box
      protein gene, DDX1. We also investigated further the pG21 expressed sequence
      previously reported to be co-amplified with MYCN. No co-amplification with the
      first 3 genes was found in any of the cell lines or tumour samples. DDX1 was
      found to be amplified along with MYCN in 4/6 (67%) cell lines and 18/38 (47%) of
      the MYCN amplified tumours. No amplification of DDX1, ODC1, RRM2 or syndecan-1
      was found in the absence of MYCN amplification. DDX1 co-amplification was
      observed to occur mainly in stage 4 or 4S patients. With the exclusion of those
      with 4S disease, patients with DDX1 co-amplification had a significantly shorter
      mean (+/- SE) disease-free interval (4.1 +/- 1.4, n = 8 months) compared with
      patients with MYCN amplification alone (19.6 +/- 4.5, n = 17) (P = 0.04, Welch's
      unpaired t-test). The pG21 sequence was identical to part of the DDX1 gene. These
      observations indicate that there is at least 1 other gene co-amplified with MYCN
      in a proportion of cases and that those patients with DDX1 co-amplification tend
      to relapse more quickly. It also implies that the MYCN amplicon is of varied size
      and/or position relative to the MYCN gene.

PMID- 9516850
TI  - Neuroblastoma cells can actively eliminate supernumerary MYCN gene copies by
      micronucleus formation--sign of tumour cell revertance?
AB  - Human neuroblastoma cell lines frequently exhibit MYCN amplification and many are
      characterised by the presence of morphologically distinct cell types. The
      neuronal cells (N-cells) and the so-called flat cells (F-cells) are thought to
      represent manifestations of different neural crest cell lineages and are
      considered to be the consequence of neuroblastoma cell pluripotency. In this
      study, various neuroblastoma cell lines were examined for micronuclei. In F-cells
      of neuroblastoma cell lines with extrachromosomally amplified MYCN, we observed
      the frequent occurrence of micronuclei. Using fluorescence in situ hybridisation
      (FISH) with a MYCN specific probe, we demonstrated that these micronuclei were
      packed with MYCN hybridisation signals. In addition, in a minor percentage of
      cells, MYCN signals occurred in clusters, adhered to the nuclear membrane and
      aggregated in nuclear protrusions. In F-cells, a substantial reduction or lack of
      amplified MYCN copies was observed. These observations let us conclude that
      extrachromosomally amplified genes can be actively eliminated from the nucleus
      resulting in a dramatic loss of amplified sequences in the F-cells. Moreover,
      reduction or loss of amplified sequences in F-cells was shown to be accompanied
      by downregulation of MYCN expression, by a decrease in proliferative activity and
      by upregulation of molecules of the major histocompatibility complex class I (MHC
      I). Interestingly, F-cells are not restricted to neuroblastoma cell cultures, but
      also occur in cell lines of other tissue origin. All F-cells share important
      biological features, interpreted as cell revertance, i.e. loss of the malignant
      phenotype and properties. This fact, together with the demonstration that
      neuroblastoma cells do not differentiate into Schwann cells in vivo [1] Ambros et
      al. NEJM 1996, 334, 1505-1511, do not support the hypothesis that F-cells
      represent Schwannian/glial differentiation in vitro. We therefore postulate that
      the elimination of amplified MYCN gene copies in cultivated neuroblastoma cells
      is in line with the phenomenon of tumour cell revertance.

PMID- 9516851
TI  - Role of neurotrophins and their receptors in human neuroblastomas: a primary
      culture study.
AB  - Expression of trk family genes are prognostic indicators of neuroblastoma.
      However, the functional role of neurotrophins and their receptors in
      neuroblastomas in vivo is still unclear. We studied the expression of
      neurotrophin receptors (trk-A, trk-B, trk-C) and their responsiveness to
      neurotrophins (NGF, BDNF, NT-3) in 25 human neuroblastomas using a primary
      culture system. The tumours in early stages and stage 4s responded to both NGF
      and NT-3, but not to BDNF, by surviving and differentiating terminally and the
      responsiveness was correlated with high levels of trk-A, especially the neuronal
      isoform. However, in many advanced stage tumours, the expression of trk-A was
      down-regulated and the response pattern to neurotrophins was diverse, without
      showing terminal differentiation. Interestingly, a stage 4 tumour with MYCN
      amplification which expressed high level of neuronal trk-A was dependent on nerve
      growth factor (NGF) for both survival and differentiation in primary culture. The
      results suggest that the NGF/trk-A signalling may be the main regulatory pathway
      for differentiation and survival of neuroblastoma in vivo and that trk-A
      overexpression may overcome aggressiveness, even of the tumour with MYCN
      amplification.

PMID- 9516852
TI  - Expression and function of Trk-C in favourable human neuroblastomas.
AB  - Human neuroblastomas express the neurotrophin receptors trk-A and trk-B.
      Favourable outcome is associated with expression of trk-A, while unfavourable,
      MYCN amplified tumours express trk-B. In this study we examined the expression of
      trk-C in primary neuroblastoma tumour-derived cell lines. We found by Northern
      blot analysis that trk-C mRNA is expressed in 14 of 55 (25%) primary tumours. Trk
      C was expressed in significantly more lower stage tumours (stage 1, 2, 4S) than
      higher stage tumours (stage 3, 4, P < 0.04). The expression of trk-C was
      correlated positively with survival and negatively correlated with MYCN
      amplification. We also studied the function of trk-C in transfected cell lines
      and found that NT-3 promotes both cell survival and differentiation. Our results
      suggest that trk-C is involved in the biology of favourable neuroblastomas.

PMID- 9516853
TI  - Activity of a 40 kDa RNA-binding protein correlates with MYCN and c-fos mRNA
      stability in human neuroblastoma.
AB  - Subclones of neuroblastic (N) and substrate adherent (S) cells have been
      established from neuroblastoma tumours cultured in vitro which differ in growth
      characteristics and MYCN expression. N cells derived from the NBL-W cell line (W
      N) express 5-fold higher levels of MYCN mRNA and 10-fold higher levels of MYCN
      protein than S cells (W-S), despite having the same MYCN copy number. In an
      effort to identify the molecular mechanisms responsible for the disparity in
      steady-state MYCN levels, the rate of MYCN mRNA degradation was measured in the
      two subclones. The half-life of MYCN mRNA in the W-N cells was approximately 45
      min compared to approximately 6 min in the W-S cells. Similarly, the half-life of
      another labile mRNA, c-fos, differed in W-N and W-S cells (30 min versus 15 min,
      respectively). The turnover of labile mRNAs is thought to be mediated by the
      interactions of trans-acting factors with AU-rich elements within the 3'
      untranslated region. RNA UV cross-linking assays using W-N cell lysate
      demonstrated abundant quantities of a protein, 40 kDa in size (p40), that bound
      specifically to AU-rich elements within the MYCN and c-fos 3' untranslated
      region. However, p40 was barely detectable in W-S cells. Our studies suggest that
      p40 may play a role in determining neuroblastoma phenotype by regulating MYCN and
      c-fos mRNA turnover.

PMID- 9516854
TI  - Activation of trk-A but not trk-B signal transduction pathway inhibits growth of
      neuroblastoma cells.
AB  - In neuroblastoma tumours, the expression of high levels of trk-A mRNA, which
      encodes the high-affinity nerve growth factor (NGF) receptor, is associated with
      good prognosis. Constitutive expression of brain-derived neurotrophic factor
      (BDNF) and variable expression of its receptor trk-B are frequently detected in
      tumours from patients with a poor prognosis. To evaluate the biological
      consequences of activation of the trk-A or trk-B signal transduction pathways in
      neuroblastoma cells, the trk-A or trk-B gene was transfected into the trk
      negative 15N neuroblastoma cell line. Clones expressing trk-A or trk-B were
      treated with specific ligands and evaluated for growth and differentiation. Both
      ligands induced neurite extension. Treatment of the 15N-trk-A clones with NGF
      inhibited proliferation (80-90% decrease), while treatment of the 15N-trk-B clone
      with BDNF had no effect (< 10% decrease). NGF-induced growth inhibition was
      concentration dependent. Such studies indicate that differential trk expression
      may affect the biology of neuroblastoma tumours and contribute to differences in
      the clinical course of patients.

PMID- 9516856
TI  - Retinoids in neuroblastoma therapy: distinct biological properties of 9-cis- and
      all-trans-retinoic acid.
AB  - We investigated the potential for 9-cis-retinoic acid in the differentiation
      therapy of neuroblastoma using an N-type neuroblastoma cell line, SH SY 5Y, as an
      experimental model. In these cells, 9-cis-retinoic acid is more effective than
      other isomers at inducing the expression of RAR-beta. An RAR-alpha-specific
      antagonist inhibited the induction of RAR-beta in response to all-trans-but not
      to 9-cis-retinoic acid. This indicates that the mechanism of gene induction by 9
      cis-retinoic acid differs markedly from all-trans-retinoic acid. 9-cis-retinoic
      acid is also better than all-trans at producing sustained morphological
      differentiation and inhibition of proliferation of SH SY 5Y cells. Although N
      type neuroblastoma cells are not thought to undergo apoptosis in response to all
      trans-retinoic acid, we observed a significant degree of apoptosis in SH SY 5Y
      cells treated with 9-cis-retinoic acid for 5 days and then cultured in the
      absence of retinoid, an effect not observed in cells treated with the all-trans
      isomer. These results suggest that 9-cis- and all-trans-retinoic acid have
      distinct biological properties and that 9-cis retinoic acid may be clinically
      effective in neuroblastoma by inducing both differentiation and apoptosis under
      an appropriate treatment regimen.

PMID- 9516857
TI  - Interleukin-1 beta converting enzyme (ICE) is preferentially expressed in
      neuroblastomas with favourable prognosis.
AB  - To determine whether interleukin-1 beta converting enzyme (ICE) plays a role in
      the programmed cell death of neuroblastoma, we studied ICE expression in primary
      tumours. In patients in stages I, II and IVS, ICE mRNA was detected in 22 of 32
      (69%) tumours, while only 5 of 26 (19%) tumours expressed ICE in stages III and
      IV (P < 0.001). ICE mRNA was expressed in 27 of 47 (57%) tumours without MYCN
      amplification, but it was not detected in any tumours with MYCN amplification (P
      < 0.01). Immunohistochemically, the cytoplasm was stained in all 15
      neuroblastomas examined. The nuclei were stained in 12 neuroblastomas without
      MYCN amplification, whereas only 1 of 3 tumours with MYCN amplification had
      positive staining in the nuclei. In ganglioneuromas, high levels of ICE mRNA were
      expressed, but immunostaining showed that the protease expression was confined to
      the cytoplasm. These observations suggest that ICE may be associated with the
      spontaneous regression often seen in favourable neuroblastomas and that
      localisation of ICE protease in the cell may be important for the cell death
      pathway. Double staining for ICE and TUNEL showed that they were co-localised in
      some nuclei, but the distribution of ICE protease expression was not necessarily
      the same as that of DNA fragmentation, suggesting that the protease expression
      probably preceded DNA fragmentation during the apoptotic process. ICE may play an
      important role in regulating the apoptotic process of neuroblastoma.

PMID- 9516855
TI  - HuD, a neuronal-specific RNA-binding protein, is a potential regulator of MYCN
      expression in human neuroblastoma cells.
AB  - HuD is one of a family of neural antigens recognised by the sera of patients with
      antibody-associated paraneoplastic encephalomyelitis. Localised exclusively to
      neurons, these proteins are among the earliest markers of the developing nervous
      system. Sequence analysis suggests that HuD is an RNA-binding protein. Hu protein
      levels were determined for the three cell types characterising human
      neuroblastoma cell lines: sympathoadrenal neuroblasts (N), substrate-adherent
      Schwann/glial/melanoblastic precursors (S) and stem cells (I) which can give rise
      to both N and S cells. Western blot analysis showed similar levels of protein in
      three N-type cell lines; S cells have no detectable Hu protein. Northern blot
      analysis indicated that N cells express all three Hu genes, HuD, HuC and Hel-N1.
      N cells, mostly from MYCN-amplified cell lines, have consistently higher steady
      state levels of MYCN mRNA than S cell counterparts. Nuclear run-on and mRNA half
      life experiments revealed no differences in transcription rate or mRNA stability
      between N and S cells from the LA-N-1 cell line, implicating differences in post
      transcriptional regulation. HuD is postulated to be instrumental in
      splicing/processing and/or stabilisation of mRNAs involved in cell growth and
      neuronal differentiation. As determined by gel-mobility shift assays, HuD fusion
      protein binds to the 3'UTR of human MYCN mRNA. Analysis of HuD deletion mutants
      has demonstrated that the first and second RNA-recognition motifs (RRMs) are
      required for binding. Whether HuD regulates MYCN expression and thereby
      influences tumour aggressiveness is of major interest.

PMID- 9516858
TI  - Somatostatin in neuroblastoma and ganglioneuroma.
AB  - Neuroblastoma, a childhood tumour of the sympathetic nervous system, may in some
      cases differentiate to a benign ganglioneuroma or regress due to apoptosis.
      Somatostatin may inhibit neuroblastoma growth and induce apoptosis in vitro and
      was therefore investigated. Using a radioimmunoassay, we found that all
      ganglioneuromas contained high somatostatin concentrations (> 16 pmol/g),
      significantly higher than neuroblastomas (n = 117, median 2.8 pmol/g), healthy
      adrenals, Wilms' tumours, phaeochromocytomas and other neuroendocrine tumours (P
      < 0.001). Neuroblastomas contained more somatostatin than control tumours (P <
      0.001-0.05). Neuroblastomas amplified for the MYCN oncogene contained less
      somatostatin than non-amplified tumours (1.2 pmol/g versus 4.0 pmol/g,
      respectively; P = 0.026). In a clinically unfavourable neuroblastoma subset (age
      > 12 months, stage 3 or 4) 16 children with high concentrations of somatostatin
      in primary tumours had a better prognosis than 23 with low somatostatin (46.7%
      versus 0% survival at 5 years, P < 0.005). Scintigraphy using 111In-pentetreotide
      identified tumours expressing high-affinity somatostatin receptors in vivo.
      However, no significant correlation was found between somatostatin receptor
      expression and peptide content in 15 tumours. Similarly, human SH-SY5Y
      neuroblastoma xenografts grown in nude rats showed low somatostatin
      concentrations, but were positive for somatostatin receptor scintigraphy.
      Treatment of these rats with the somatostatin analogue octreotide seemed to
      upregulate in vivo receptor expression of somatostatin and vasoactive intestinal
      peptide more effectively than 13-cis retinoic acid. In conclusion, somatostatin
      in neuroblastoma is associated with differentiation to benign ganglioneuromas in
      vivo and favourable outcome in advanced tumours. Furthermore, somatostatin
      receptor scintigraphy may identify tumours with high-affinity receptors in
      children that might benefit from targeted therapy using synthetic somatostatin
      analogues.

PMID- 9516859
TI  - Monoclonal antibody to human Trk-A: diagnostic and therapeutic potential in
      neuroblastoma.
AB  - 5C3 is a murine IgG1 antibody specific for the nerve growth factor (NGF) docking
      site of the human p140 trk-A receptor, with no cross-reactivity with human trk-B.
      In vitro, 5C3 and its Fab mimic the effects of NGF, a neurotrophin mediating
      growth and differentiation of neural crest-derived cells. When labelled with
      radioisotope, 5C3 images human trk-A positive tumours in vivo. More importantly,
      5C3 induces regression of human trk-A positive tumours in rodents. We therefore
      investigated the value of 5C3 in detecting trk-A expression in human
      neuroblastoma by immunohistochemistry. 5C3 reactivity was detected in 73 of 113
      neuroblastoma specimens and correlated strongly with localised/4s disease (55/60)
      with either a homogeneous or mixed pattern. Among stage 4 neuroblastoma, only
      18/53 had homogeneous or mixed trk-A expression. 5C3 did not react with 46/48
      other human malignancies, but was positive in 1 melanoma and 1 Wilms' tumour
      specimen. The prognostic, imaging and NGF-mimetic properties of antibody 5C3 and
      its derivatives may offer alternatives for the diagnosis and treatment of
      neuroblastoma.

PMID- 9516860
TI  - The current contribution of molecular factors to risk estimation in neuroblastoma
      patients.
AB  - The association of molecular characteristics with prognosis has been reported,
      but not their relationship with each other and their impact in the context of
      known clinical risk factors. In this study, data of 1249 consecutive intent-to
      treat-neuroblastoma patients with more than 1 year follow-up were examined by
      multivariate analysis using loglinear and Cox proportional hazard regression
      models on a stage-related basis (stages 1-3: 600, 4S: 116, 4: 533). In a first
      step, risk factors were identified from 18 selected clinical variables, and risk
      groups defined. The second step investigated whether molecular characteristics
      (MYCN, LOH 1p, del 1p, CD44, N-ras, NGF-R, bcl-2, APO-1 (CD95)) contributed
      additional prognostic information to the model. The loglinear model demonstrated
      several interactions between clinical factors. By the Cox regression model, seven
      independent clinical risk factors were found for stages 1-3, seven for stage 4
      and two for stage 4S. By subsequent introduction of all molecular variables, MYCN
      amplification only added significant prognostic information to the clinical
      factors in localised and stage 4 neuroblastoma. The models allowed the definition
      of risk groups for stages 1-3 patients by age (e beta = 5.09) and MYCN (e beta =
      4.26), for stage 4 by MYCN (e beta = 2.78) and number of symptoms (e beta = 2.44)
      and for stage 4S by platelet count (e beta = 3.91) and general condition (e beta
      = 2.99). Molecular factors and in particular MYCN contribute significantly to
      risk estimation. In conjunction with clinical factors, they are powerful tools to
      define risk groups in neuroblastoma.

PMID- 9516861
TI  - Correlation of MYCN amplification, Trk-A and CD44 expression with clinical stage
      in 250 patients with neuroblastoma.
AB  - In contrast to MYCN amplification, expression of either trk-A or CD44 in
      neuroblastoma is a favourable prognostic factor and were therefore investigated
      in tumours from 250 patients. One hundred and eleven localised/4s (Group 1) and
      139 stage 4 (Group 2) tumours were analysed. MYCN copy number was obtained by
      Southern blotting or PCR amplification and was detected in 28 stage 4 tumours.
      Trk-A and CD44 expression was detected by immunoperoxidase staining using murine
      monoclonal antibodies 5C3 and L178, respectively. Expression was scored as
      positive (homogeneous), mixed (heterogeneous) or non-reactive (negative). Trk-A
      expression was found in 95% of Group 1 tumours and 49% of Group 2 tumours. CD44
      expression was found in 100% of Group 1 tumours, the majority of which had a
      strong homogeneous expression. Lack of CD44 expression occurred in 25% of
      tumours, all stage 4 neuroblastoma. Of the 28 MYCN amplified tumours, 27/28 (96%)
      were trk-A negative, and 13/28 (46%) CD44 negative. We conclude that (1) a
      significant percentage of stage 4 neuroblastoma express either or both trk-A and
      CD44, (2) the absence of CD44 expression is highly restricted to stage 4
      neuroblastoma and is associated with the lack of trk-A expression, (3) trk-A
      negativity among CD44-positive tumours is associated with stage 4 neuroblastoma
      and (4) the absence of trk-A expression is highly correlated with MYCN
      amplification.

PMID- 9516862
TI  - Clinical relevance of CD44 cell surface expression and MYCN gene amplification in
      neuroblastoma.
AB  - This multicentric analysis of tumours obtained from 140 patients with
      neuroblastoma confirms that the lack of CD44 expression is a highly significant
      factor of poor prognosis and, as previously published in multivariate analysis of
      the four factors, i.e. MYCN amplification, CD44 expression, age and tumour stage,
      CD44 expression and tumour stage were the only independent prognostic factors of
      event-free survival (Combaret et al., J Clin Oncol 1996, 14, 25-34). Furthermore,
      CD44 analysis affords significant prognostic discrimination in subgroups of
      patients with or without MYCN amplified tumours, both in low-stage neuroblastomas
      and high-grade neuroblastomas. In the subgroup of patients with low-stage
      neuroblastoma and the stage 4 subgroup, CD44 was the only independent prognostic
      factor for the prediction of event-free survival in a multivariate analysis. In
      conclusion, CD44 is one of the most powerful factors for predicting clinical
      outcome in neuroblastoma at the time of initial staging.

PMID- 9516863
TI  - Screening for neuroblastoma is ineffective in reducing the incidence of
      unfavourable advanced stage disease in older children.
AB  - Neuroblastoma exhibits many characteristics which would suggest that preclinical
      detection may improve outcome. The Quebec Neuroblastoma Screening Project was
      initiated to determine whether mass screening could reduce mortality in a large
      cohort of infants. All 476,603 children born in the province of Quebec during a 5
      year period of time (1 May 1989 to 30 April 1994) were eligible for
      determinations of urinary catecholamine metabolites at 3 weeks and 6 months of
      age. Children with positive screening were referred to one of four paediatric
      cancer centres in Quebec for uniform evaluation and treatment. Standardised
      incidence ratios (SIRs) were calculated for neuroblastoma in Quebec and two
      comparable population-based controls during the same period of time using similar
      ascertainment procedures. Compliance with screening in Quebec was 91% at 3 weeks
      (n = 425,816) and 74% at 6 months (n = 349,706). Up to 31 July 1995 with a follow
      up of the birth cohort of 15-75 months, 118 cases of neuroblastoma were
      diagnosed, 43 detected preclinically by screening, 20 detected clinically prior
      to screening at 3 weeks of age and 55 detected clinically after 3 weeks of age
      having normal screens (n = 52) or never screened (n = 3). Based on data from
      concurrent control populations, 54.5 cases of neuroblastoma would have been
      expected in Quebec during the study period for an SIR of 2.17 (95% CI 1.79-2.57,
      P < 0.0001). For the two control groups, the overall SIR was 1.00 (NS). SIRs for
      Quebec by age at diagnosis in yearly intervals show a marked increased incidence
      under 1 year of age (SIR = 2.85, 95% CI 2.26-3.50), with no reduction in
      incidence in subsequent years. We conclude that screening for neuroblastoma
      markedly increases the incidence in infants without decreasing the incidence of
      unfavourable advanced stage disease in older children. It is unlikely that
      screening for neuroblastoma in infants will reduce the mortality of this disease.

PMID- 9516865
TI  - Survival from non-stage 4 neuroblastoma without cytotoxic therapy: an analysis of
      clinical and biological markers.
AB  - The clinical characteristics of 43 patients (pts) and the biological features of
      their non-stage 4 neuroblastoma (11, 3, 15, 7 and 7 with stages 1, 2A, 2B, 3 and
      4S, respectively) all managed initially without cytotoxic therapy at Memorial
      Sloan-Kettering Cancer Center are summarised. We staged patients by the
      International Neuroblastoma Staging System and measured their urine and serum
      tumour markers. Tumour MYCN copy number, chromosomal ploidy, chromosome 1p
      deletion, Shimada histopathology, trk-A and CD44 expression were analysed. Among
      patients with localised tumour (n = 36), 13 had residual disease after initial
      surgery, 19 had regional lymph node invasion and 6 had epidural involvement (2 of
      6 being paraplegic). All 7 stage 4S patients had liver tumours, 3 had bone marrow
      involvement and 3 had lymph node involvement. The most common adverse biological
      markers were unfavourable histopathology (9/40 evaluable tumours) and diploidy
      (7/39 tumours tested). At a median follow-up of 50+ months, 42 patients are alive
      and well (5 with evidence of disease), and 1 patient in remission died of
      encephalopathy. Progressive/recurrent disease occurred in 12 patients, 1 stage
      2A, 2 stage 2B, 4 stage 3 and 5 stage 4S. Chemotherapy was eventually used in 4
      patients: a 3-year-old stage 2B patient who developed stage 4; a 2-year-old whose
      recurrent tumour had poor-risk biological markers; a 1-year-old whose recurrent
      stage 3 disease infiltrated a vertebral body and a stage 4S infant with
      respiratory impairment from progressive hepatomegaly. Three of the treated
      patients had diploid tumours. We conclude that non-stage 4 is of itself a strong
      predictor of a favourable outcome. Diploidy, unfavourable histopathology and
      unresectable tumours were associated with disease progression. However, evolution
      of local-regional tumour into distant metastatic stage 4 disease is not typical
      of neuroblastoma.

PMID- 9516864
TI  - The International Neuroblastoma Risk Groups (INRG): a preliminary report.

PMID- 9516866
TI  - Event-free survival of children with biologically favourable neuroblastoma based
      on the degree of initial tumour resection: results from the Pediatric Oncology
      Group.
AB  - We analysed the 2-year event-free survival (EFS) of 49 patients 1 year of age and
      older, with stage 2B or 3 neuroblastoma, treated on Pediatric Oncology Group
      protocols 8742 and 9244, with respect to the degree of tumour resection at
      diagnosis. The 2-year EFS rate for 21 children whose tumours were completely
      resected at diagnosis was 85% (SE = 10%) compared with an EFS rate of 70% (SE =
      9%) for the 28 children whose tumours were incompletely resected at diagnosis.
      Despite the observed trend in favour of complete resection, these EFS curves were
      not statistically significantly different (P = 0.259). Patients with favourable
      Shimada histology tumours had an EFS rate of 92% (SE = 7%) compared with a rate
      of 58% (SE = 15%) for patients with unfavourable histology tumours. EFS curves
      for the two histologic groups were significantly different (P = 0.009). The
      impact of aggressive surgery and adjuvant chemotherapy on the outcome of patients
      with biologically favourable regional neuroblastoma is still unclear.

PMID- 9516867
TI  - Stage IV neuroblastoma in patients over 1 year of age at diagnosis: consolidation
      of poor responders with combined busulfan, cyclophosphamide and melphalan
      followed by in vitro mafosfamide-purged autologous bone marrow transplantation.
AB  - In an attempt to improve the poor prognosis of poor responders with stage IV
      neuroblastoma, a new combined high-dose chemotherapy conditioning regimen was
      tested. Event-free and overall survival, as well as the incidence of
      complications, were analysed. Twenty-five children aged 12-146 months at
      diagnosis entered this study. All were in complete remission (CR) at the time of
      high-dose chemotherapy. Two or three different protocols had been necessary for
      them to achieve a CR. High-dose chemotherapy consisted of a combination of
      busulfan (600 mg/m2), cyclophosphamide (4400 mg/m2) and melphalan (140 mg/m2). It
      was followed by autologous bone marrow transplantation (ABMT). The bone marrow
      graft was purged in vitro with mafosfamide. The probability of event-free
      survival (EFS) at 5 years post-ABMT was 34%, compared to < 8% in a historical
      series. Toxicity was severe but manageable and 2 complication-related deaths were
      observed. Veno-occlusive disease was the most frequent extrahaematopoietic
      complication encountered, but its outcome was always favourable. By using a very
      intensive conditioning regimen consisting of a combination of three alkylating
      agents, the EFS of poor responders with metastatic neuroblastoma was improved and
      similar to that of good responders. When compared with a previously published
      similar series of patients, the improvement in survival appears probably related
      to intensification of the conditioning regimen.

PMID- 9516868
TI  - 1070 myeloablative megatherapy procedures followed by stem cell rescue for
      neuroblastoma: 17 years of European experience and conclusions. European Group
      for Blood and Marrow Transplant Registry Solid Tumour Working Party.
AB  - 1070 myeloablative procedures followed by stem cell rescue for neuroblastoma are
      reviewed. These 1070 procedures are part of the European Group for Blood and
      Marrow Transplant (EBMTG) registry from the last 17 years (in 4536 patients). In
      1070 neuroblastoma patients, survival at 2 years was 49%, at 5 years, 33% and
      relapses were observed as late as 7 years post-BMT (bone marrow transplant).
      However, 5-year survivors after megatherapy with BMT for stage 4 disease do have
      an 80% chance of becoming a long-term survivor. When BMT had been used in first
      complete response (CR1) no salvage was possible, whereas 15% survivors may be
      seen if BMT is used for the first time at relapse. Infants with stage 4
      neuroblastoma had a 17% toxic death rate and indication in this group is
      exceptional and not recommended. In a matched cohort (17 allogeneic and 34
      autologous), autologous stem cell rescue (SCR) was shown to be at least equal to
      allogeneic SCR. Multivariate analysis of clinical prognostic factors in children
      with stage 4 disease over 1 year showed that event-free survival was mainly
      influenced by two adverse factors before the megatherapy procedure: persisting
      skeleton lesions (99Tc and/or mIBG scan positive) as well as persisting bone
      marrow (BM) involvement.

PMID- 9516869
TI  - Liver stem cells: when the going gets tough they get going.
AB  - The ability of the liver to regenerate is widely acknowledged, and this is
      usually accomplished by the entry of normally proliferatively quiescent
      hepatocytes into the cell cycle. However, when hepatocyte regeneration is
      impaired, small bile ducts proliferate and invade into the adjacent hepatocyte
      parenchyma. In humans and experimental animals these ductal cells are referred to
      as oval cells, and their association with defective regeneration has led to the
      belief that they are the progeny of facultative stem cells. Oval cells are of
      great biological interest since they may represent a target population for
      hepatic carcinogens, and they may also be useful vehicles for ex vivo gene
      therapy for the correction of inborn errors of metabolism. The ability of oval
      cells to differentiate into hepatocytes has been demonstrated unequivocally.
      However, this process only occurs when the regenerative capacity of hepatocytes
      is overwhelmed, and thus, unlike the intestinal epithelium, the liver is not
      behaving as a classical continually renewing stem cell-fed lineage.

PMID- 9516871
TI  - Influence of treatment with immunosuppressive drugs in mice chronically infected
      with Trypanosoma cruzi.
AB  - Latent Trypanosoma cruzi infection may be reactivated in immunosuppressed
      individuals, with unusual clinical patterns, such as meningoencephalitis, pseudo
      neoplastic lesions in the central nervous system, and myocarditis with numerous
      parasites in the heart muscle. To investigate this problem 68 Swiss mice
      chronically infected with different strains of T. cruzi were treated with
      different combinations of immunosuppressive drugs (azathioprine, cyclosporine and
      betamethasone), in such a way as to imitate the situation during post
      transplantation treatment. Mortality varied from 6 to 25% in treated mice. There
      were no deaths in untreated controls. Normal mice have been submitted to the same
      schedules of immunosuppression as controls of treatment and no deaths were
      registered during treatment. Chronically infected mice showed significant
      elevation of total number of leukocytes and lymphocytes in comparison with intact
      controls; a significant decrease in blood leukocytes and lymphocytes occurred
      post-treatment in two of the treated experimental groups. Exacerbation of
      myocarditis and myositis and a high incidence of brain lesions, with focal
      necrosis, granulomatous lesions and glial proliferation even in the absence of
      parasites were present in immunosuppressed mice but not in infected controls.
      Although differing in some aspects from Chagas' disease in immunosuppressed
      humans, the murine model did show some features that resembled it, especially the
      peculiar pattern of central nervous system involvement.

PMID- 9516870
TI  - Effect of maternal cholestasis on the kinetics of bile acid transport across the
      canalicular membrane of infant rat livers.
AB  - A reversible impairment in the ability of the liver to secrete cholephilic
      compounds has been reported to exist in infant rats born from mothers with
      surgically induced complete cholestasis during the last third of the pregnancy.
      Canalicular plasma membranes (CPM) were purified from livers obtained from 4 and
      8 week-old offspring of healthy or cholestatic rats. Using radiolabelled
      glycocholic acid (GC) and a rapid filtration technique, bile acid transport by
      CPM vesicles in the presence of 3 mM ATP plus an ATP-regenerating system was
      measured at varying substrate concentrations. Kinetic parameters were calculated
      by nonlinear regression analysis. Similar values for the apparent affinity
      constant (Kt) were found in all experimental groups (approximately 350 microM).
      The value of the maximal velocity of the transport (Vmax) was similar for CPM
      obtained from control animals at 4 or 8 weeks of age (approximately 1.5 nmol/20
      s/mg protein). In the offspring of cholestatic mothers the Vmax value was not
      different from that found in control animals as far as 4 week-old rats were
      concerned. However, Vmax in the 8 week-old group from cholestatic mothers was two
      fold higher than that found in the rest of the experimental groups. Thus, the
      efficiency of transport, defined as Vmax/Kt, was very similar in all experimental
      groups, except in the group of 8 week-old offspring of cholestatic mothers, where
      this value was 60% higher. Isolated livers obtained from this group were able to
      secrete a tracer dose of radiolabelled GC (11.25 nmol) into bile significantly
      faster than isolated livers obtained from control animals of the same age (8
      weeks). In sum, these results indicate that, in young infant rats (4 week-old),
      in which the maximal secretion rate for bile acids was reduced by maternal
      cholestasis during pregnancy, the kinetics of ATP-dependent bile acid transport
      across the canalicular membrane were not affected. By contrast, in older infant
      rats (8 week-old), in which the overall ability of the liver to secrete bile
      acids seems to be restored to normality, the efficiency of the canalicular
      transport system was actually enhanced. This suggests the existence of
      compensation at the level of the canalicular membrane transfer and thus that
      there is another hitherto unidentified mechanism involved in bile acid secretion.

PMID- 9516872
TI  - Experimental myelitis caused by herpes simplex virus type 2 in C57BL/6N and
      BALB/cN mice.
AB  - Intraperitoneal and intracranial inoculation of herpes simplex virus type 2 (HSV
      2) into BALB/cN and C57BL/6N mice was carried out to induce experimental
      myelitis. The myelitis was clearly observed in C57BL/6N mice following
      intraperitoneal inoculation. Within 24 hours before death, the mice showed
      urinary and rectal incontinence and paraplegia of the hind legs. Randomly
      distributed, severe necrosis was demonstrated in the spinal cord, mainly at the
      lower cord. In BALB/cN mice the clinical symptoms were not clearly observed, as
      the mice died shortly after their onset. Although spinal cord necrosis was more
      prominent in C57BL/6N mice than BALB/cN mice, brain necrosis was only found in
      the latter, and not in the former. Both strains of mouse showed marked nuclear
      pyknosis of the nerve cells and slight nuclear pyknosis of the astrocytes in the
      brain where HSV 2 antigen was demonstrated immunohistochemically. The antigen was
      also detected in the necrotic spinal cord. In contrast, intracranial inoculation
      of the virus into both strains did not cause myelitis. Spinal cord necrosis was
      not demonstrated and virus DNA was not detected, by PCR, in spinal cord samples.
      In the brain, however, the virus was demonstrated by both PCR and
      immunohistochemistry.

PMID- 9516873
TI  - Effect of methylprednisolone on the ulceration, matrix metalloproteinase
      distribution and eicosanoid production in a model of colitis in the rabbit.
AB  - This study has examined the response of a rabbit model of inflammatory bowel
      disease to methylprednisolone. Colitis was induced in the colon of rabbits with
      40 mg trinitrobenzenesulphonic acid in 25% ethanol (TNBS). The effect of
      methylprednisolone (0.5 mg/kg/day) on the development of colitis was determined
      at one week, by examining the colon's macroscopic and microscopic appearance, the
      distribution of matrix metalloproteinases (MMPs) and by measuring eicosanoid
      production. Although there was no difference in the area of ulcerated colonic
      tissue in the treated and untreated TNBS animals, the increase in
      polymorphonuclear leucocytes was significantly reduced in TNBS rabbits given
      methylprednisolone. The only difference in the distribution of MMPs was a
      reduction in the number of polymorphonuclear leucocytes containing gelatinase B.
      The release of immunoreactive PGE2 and LTB4, but not 6-keto PGF1 alpha, was
      increased in the TNBS animals and was unchanged by methylprednisolone. These
      results show that methylprednisolone does not modify the injury produced by TNBS
      in this model despite reducing the infiltration of polymorphonuclear leucocytes.
      Hence it suggests that these cells do not contribute to the injury observed, are
      not the source of the eicosanoids and that gelatinase B is not required in the
      healing process in this model.

PMID- 9516874
TI  - Impaired human coronary artery distensibility by atherosclerotic lesions: a
      mechanical and histological investigation.
AB  - The objective of this study was to evaluate the relationship between human
      coronary artery distensibility and vessel wall morphology assessed by
      histomorphometry. Coronary artery pressure-cross-sectional area relations and
      distensibility were studied in excised autopsy hearts by means of a balloon-based
      impedance planimetric technique 2 cm from the aortic orifice of the arteries.
      Later the hearts were perfusion fixed at 100 mm Hg and cross-sectioned 17, 20 and
      23 mm distal to the aortic orifice. The areas of lumen, intima and media were
      measured. Nineteen left anterior descending coronary arteries (LAD) and 15 right
      coronary arteries (RCA) from 25 hearts (12 women and 13 men) were investigated.
      The age of the subjects was 48-97 years (mean 73.8 years). Non-linear relations
      were found between balloon pressure and coronary cross-sectional area (according
      with the function y = a + bx0.5) and between balloon pressure and coronary
      distensibility, but there were no differences in these relations between the LAD
      and RCA. Subjects' age was positively correlated with wall thickness (r = 0.44, P
      < 0.05), intima area (r = 0.46, P < 0.01) and media area (r = 0.44, P < 0.05) of
      the coronary arteries. Additionally, the distensibility at low pressures was
      inversely correlated with arterial wall thickness (r = -0.37, P < 0.05). When
      focusing only on arteries with concentric atherosclerotic lesions, distensibility
      at low pressures was inversely correlated with arterial wall thickness (r = 
      0.57, P = 0.01) and intima area (r = -0.53, P < 0.05). Arteries with concentric
      lesions were less distensible at low pressures compared with arteries having
      eccentric lesions (5.4 +/- 0.8.10(-2) vs. 3.6 +/- 0.7.10(-2) kPa-1, P < 0.05) but
      this difference was absent at higher pressures. No difference in coronary artery
      distensibility was found between men and women. Age and distensibility were not
      correlated. These findings may have in vivo implications for complications to
      angioplasty procedures such as recoil and restenosis.

PMID- 9516875
TI  - Antiphospholipid syndrome.

PMID- 9516876
TI  - Neurological paraneoplastic syndromes.
AB  - Paraneoplastic neurological syndromes are uncommon, however, their diagnosis is
      of major practical importance. The identification of antibodies in the serum or
      cerebrospinal fluid in central nervous system paraneoplastic syndromes confirms
      the clinical diagnosis of a paraneoplastic syndrome and allows early
      identification of an underlying tumour at a stage when it is localised and more
      amenable to treatment. The failure to identify antibodies in patients with
      characteristic presentations of underlying neurological paraneoplastic syndromes
      does not exclude an underlying cancer. Necrotising myelopathy, dermatomyositis,
      and chronic inflammatory demyelinating polyneuropathy all occur more frequently
      than expected in patients with cancer but autoantibodies have not yet been
      identified. Although significant advances have been made in diagnosis, further
      research is needed in the detection of autoantibodies and the elucidation of
      their role in the aetiology of neurological disease.

PMID- 9516877
TI  - Pulmonary alveolar proteinosis: diagnosis using routinely processed smears of
      bronchoalveolar lavage fluid.
AB  - AIMS: For the diagnosis of pulmonary alveolar proteinosis from bronchoalveolar
      lavage specimens it is normally necessary to make an ultrastructural examination.
      However, this is thought to be impractical for bronchoalveolar lavage specimens
      that have been routinely fixed in ethanol. In the present study, bronchoalveolar
      lavage cytology smears on slide glasses were examined directly ultrastructurally
      to make a diagnosis of pulmonary alveolar proteinosis. METHODS: Bronchoalveolar
      lavage smears from three pulmonary alveolar proteinosis patients were stained
      with Papanicolaou and periodic acid-Schiff (PAS) for identification of amorphous
      globular structures. Subsequently, they were refixed with glutaraldehyde and
      osmium tetroxide, and embedded in epoxy resin. Ultrathin sections were cut and
      examined ultrastructurally. RESULTS: Papanicolaou stained specimens from
      pulmonary alveolar proteinosis patients contained scattered amorphous or granular
      globules, 20-50 microns in diameter, which were PAS positive. Ultrastructural
      examination of the globules revealed multilamellated structures, characteristic
      of pulmonary alveolar proteinosis, in all cases. CONCLUSIONS: In general, it is
      thought that the morphological diagnosis of pulmonary alveolar proteinosis from
      bronchoalveolar lavage specimens requires both cytological and ultrastructural
      examination. However, the amorphous globules evident on cytology smears proved to
      contain multilamellated structures so that they can themselves be used as
      diagnostic evidence.

PMID- 9516878
TI  - A review of 50 consecutive cytology cell block preparations in a large general
      hospital.
AB  - AIMS: To review consecutive cell block preparations of cytological specimens in a
      large general hospital. METHODS: 50 cell blocks were made over an 18 month period
      in which about 1900 fine needle aspirations (FNAs) were performed. The aspirator
      was a cytologist or, for image guided FNAs, a radiologist with a cytologist at
      hand to collect the specimen. Forty eight cell blocks were from FNAs and two were
      from serous fluids. RESULTS: The cellularity of the cell blocks was inadequate in
      only four preparations. The main motive for making cell blocks was to obtain
      tissue for immunohistochemistry. This was performed on 28 cases and a total of
      107 immunostained sections were produced. The most common diagnostic dilemma was
      between carcinoma and melanoma, and the second most common between carcinoma and
      lymphoma. Consequently cytokeratin, S-100, and LCA were the most frequently used
      antibodies. At least one of these three antibodies was positive in 17 cases. Five
      cases were immunostained only for prognostic breast markers. CONCLUSIONS: The use
      of cell block immunohistochemistry is a reliable and technically unsophisticated
      aid in the cytological examination of tumours other than lymphomas. Success
      depends on having highly experienced aspirators that reliably obtain sufficiently
      cellular material.

PMID- 9516879
TI  - Intestinal immune cells in Strongyloides stercoralis infection.
AB  - BACKGROUND: Strongyloides stercoralis can cause a wide spectrum of disease in
      man, ranging from a chronic asymptomatic infection to a hyperinfective, often
      fatal syndrome. In rodents, spontaneous expulsion of Strongyloides spp occurs
      after experimental infection. Mast cells, goblet cells, and eosinophils have been
      identified as possible effectors of this expulsion. AIMS: To investigate
      intestinal histopathology and mucosal immunity in immunocompetent patients with
      chronic S stercoralis infection. METHODS: Jejunal biopsies were performed in 19
      immunocompetent patients with a positive stool examination for S stercoralis and
      few or no symptoms, and in seven healthy controls. Specimens were processed for
      histopathological analysis and stained by the immunoperoxidase technique, using
      the following monoclonal antibodies: CD2, CD3, CD4, CD8, anti-T cell receptor
      (TcR) gamma/delta, RFD1 and RFD7 (two different macrophage markers), Ki67+
      (proliferating) cells, antihuman leucocyte antigen (HLA)-DR, and anticollagen IV.
      In addition, CD25+ cells, mast cells, IgE expressing cells, calprotectin
      containing cells, and neutrophil elastase positive cells were stained by the
      alkaline phosphatase method. RESULTS: Jejunal morphology and the numbers of
      different T cell subsets, mast cells, IgE expressing cells, eosinophils, and
      goblet cells were unaffected by S stercoralis infection. Conversely, the numbers
      of mature macrophages and dividing enterocytes in the crypts were reduced
      significantly. Crypt enterocytes did not express HLA-DR in both groups. The
      expression of HLA-DR by villus enterocytes was also comparable in patients and
      controls. There were no activated (CD25+) cells in the mucosa of either patients
      or controls. CONCLUSIONS: Compared with seven healthy uninfected volunteers, a
      group of 19 Brazilians with clinically mild strongyloides infection showed no
      abnormality of mucosal structure and no increase in non-specific inflammatory
      cells. Likewise, there was no increase in mucosal T cells or macrophages.

PMID- 9516880
TI  - Evaluation of a new enzyme immunoassay for Clostridium difficile toxin A.
AB  - AIM: To evaluate a new enzyme immunoassay (EIA) method for detection of
      Clostridium difficile toxin by comparing it to cytotoxicity assay. To investigate
      the nature of false negative and false positive EIA results by evaluating
      clinical and therapeutic parameters. METHODS: 737 consecutive diarrhoeal
      specimens collected from patients clinically suspected of having C difficile
      colitis were tested for the presence of C difficile toxin by EIA for toxin A and
      by cytotoxicity assay. Clinical data were evaluated in all cases positive by
      either method. RESULTS: With the cytotoxicity assay as a gold standard, the
      specificity of EIA for toxin detection was 99.3% and the sensitivity was 62.2%.
      No false negative EIA specimens were obtained from patients already being treated
      for C difficile colitis. Among patients with cytotoxicity positive specimens,
      those with EIA positive samples had no clinical features distinguishing them from
      patients with EIA negative samples. CONCLUSIONS: Although specific, the new EIA
      method directed against toxin A lacks sensitivity compared to cytotoxicity. False
      negative EIA tests are not associated with concurrent treatment for C difficile
      colitis nor with any specific clinical features examined in our study.

PMID- 9516881
TI  - Abnormal pancreolauryl tests in coeliac disease: lack of correlation with the
      degree of intestinal mucosal damage.
AB  - AIMS: To determine the frequency of abnormal pancreolauryl tests in untreated and
      treated adults with coeliac disease and to see whether abnormalities in treated
      coeliac patients correlate with the degree of recovery of intestinal morphology
      or brush border enzyme activity. METHODS: Pancreolauryl tests were performed in a
      study population of 57 adult coeliac patients (25 on gluten containing diets and
      32 on gluten free diets), 59 symptomatic controls, and eight patients with
      pancreatic disease. Brush border enzyme activity and morphological assessment
      were performed on small intestinal biopsies in 27 of the treated coeliac
      patients. RESULTS: Forty per cent of untreated coeliac patients and 18% of
      treated coeliac patients had abnormal tests. In treated coeliac patients, no
      significant correlation was detected between the pancreolauryl test result and
      either brush border enzyme activity or morphological parameters. CONCLUSION:
      Abnormal pancreolauryl test results are common in untreated and treated adult
      coeliac disease patients. Abnormalities in treated coeliac patients do not
      correlate with the degree of recovery of small intestinal morphology or brush
      border enzymes.

PMID- 9516882
TI  - Correlation of fine needle aspiration cytology and frozen section biopsies in the
      diagnosis of thyroid nodules.
AB  - AIMS: To evaluate the correlation of fine needle aspiration (FNA) cytology and
      frozen section biopsy in the diagnosis of thyroid nodules. METHODS: The medical
      records of 662 patients who underwent FNA cytology of the thyroid and thyroid
      surgery were analysed. Frozen section biopsies were taken from 586 of the 662
      patients. The diagnostic correlations of FNA cytology, frozen section, and both
      FNA cytology and frozen section with definitive histological assessment were
      evaluated. RESULTS: Among the 662 patients who received FNA cytology, there were
      356 cases (53.8%) diagnosed as benign, 114 cases (17.2%) as malignant, 148 cases
      (22.4%) as indeterminate, and 44 cases (6.6%) as unsatisfactory. The positive
      predictive value for the detection of malignancy by FNA cytology was 92.1% and
      the negative predictive value was 95.2%. The incidence of malignancy in the
      indeterminate cytological diagnosis was 23%. The diagnosis from frozen sections
      was benign in 445 cases (75.9%), malignant in 134 cases (22.9%), and deferred in
      7 cases (1.2%). By frozen section, the positive and negative predictive values
      were 97% and 95.5%, respectively. Diagnostic accuracy up to 98% was achieved when
      FNA cytology and frozen section diagnoses were in agreement. No false positives
      were observed when FNA cytology and frozen sections were both positive for
      malignancy. When FNA cytology and frozen section diagnoses were discordant,
      frozen section showed a higher accuracy (78.9%) than FNA cytology (21.1%). In the
      face of an indeterminate or unsatisfactory cytological diagnosis, the diagnostic
      accuracy of frozen sections reached 92.6%. CONCLUSIONS: The results confirm that
      FNA cytology is a useful tool in the initial evaluation of thyroid nodules.
      Intraoperative frozen section is a valuable procedure to confirm the cytological
      diagnosis and identify malignancy in patients with indeterminate or
      unsatisfactory cytological diagnosis. With reliance on frozen sections as an
      intraoperative guide of thyroid surgery, the possibility of unnecessary extensive
      surgery and the need for the second operation are considerably lower.

PMID- 9516883
TI  - The impact of blood culture reporting and clinical liaison on the empiric
      treatment of bacteraemia.
AB  - AIMS: To assess the impact of blood culture results and early clinical liaison on
      the treatment of patients with bacteraemia. METHODS: 123 patients with
      significant positive blood cultures were followed over a nine month period in a
      620 bed teaching hospital. The impact of early blood culture reporting and
      clinical liaison on the cost and appropriateness of treatment was assessed.
      RESULTS: Empiric treatment was started before the Gram stain result in 107 (87%)
      patients. Treatment was altered on the basis of the Gram stain result in 39 (36%)
      of these patients, and on culture and sensitivity results in 53 (50%). The
      spectrum of antibiotic treatment was narrowed in 58 (54%) of these; 20 (19%) on
      Gram stain result alone. This resulted in a 42% reduction in daily antibiotic
      costs in patients who had received empiric treatment. Empiric treatment did not
      follow the hospital antibiotic policy in 49 (46%) of the patients treated. In
      patients where empiric treatment was not in accordance with hospital policy, 21
      (44%) had an isolate resistant to the empiric treatment used; while in patients
      who received agents in accordance with hospital policy only one (1.7%) had a
      resistant isolate (p < 0.05). Patients who died (11 (9%)) were less likely to
      have received empiric treatment in accordance with the antibiotic policy,
      although this did not reach statistical significance (p = 0.1). CONCLUSION: Early
      reporting of Gram stain results from blood cultures, combined with early clinical
      liaison, results in more rational and cost effective treatment.

PMID- 9516884
TI  - Ulceration of the ileum in Crohn's disease: correlation with vascular anatomy.
AB  - BACKGROUND: Ileal ulcers in Crohn's disease tend to lie along the same side of
      the bowel wall as the mesenteric attachment; the mesenteric and antimesenteric
      borders are supplied by short and long arteries, respectively. AIM: To examine
      the localisation of ileal Crohn's ulcers and to test the hypothesis that
      predilection of Crohn's ulcers for the ileal mesenteric margin is explained by
      the existence of end arteries that supply the mesenteric margin. METHODS: The
      localisation of ulcers in the bowel wall was examined in eight resection
      specimens of Crohn's disease of the terminal ileum. The vascular anatomy of
      normal terminal ileum (n = 8) and proximal jejunum (n = 8) postmortem specimens
      was studied; isolated long and short vessels were ligated before perfusion in
      four of these specimens. RESULTS: All eight specimens of Crohn's disease of the
      terminal ileum showed longitudinal ulceration along the mesenteric margin. In the
      postmortem study, the submucosal vascular plexus derived from ileal, but not
      jejunal short vessels, comprised end arteries with little or no communication
      with the submucosal plexus arising from long vessels. Prior ligation of ileal,
      but not jejunal, short vessels resulted in a filling defect of the submucosal
      plexus along the mesenteric margin in three of the four specimens. Ligation of
      ileal and jejunal long vessels did not affect carbon ink perfusion of the bowel
      wall. CONCLUSIONS: In the human terminal ileum, the short vessels supplying the
      mesenteric margin are end arteries, and their pathological occlusion might cause
      ischaemia of this region. These findings support a vascular hypothesis for
      Crohn's disease and may explain, in part, both the ileal and mesenteric
      distribution of Crohn's disease ulcers.

PMID- 9516886
TI  - Continuing medical education for pathologists: an evaluation of the Royal College
      of Pathologists' Wessex pilot scheme.
AB  - AIM: To discover the attitudes to continuing medical education (CME) of the
      Wessex pathologists who participated in the Wessex CME pilot scheme and to
      identify their preferences and difficulties in pursuing CME activities. METHOD:
      The views of pathologists in the scheme were collected during a period of one
      year using workshops and discussions. A confidential, anonymous postal
      questionnaire based on these issues was sent to the 103 pathologists in Wessex
      who participated in the pilot scheme. RESULTS: A 64% response rate was obtained.
      The respondents identified lack of time and funded study leave as major barriers
      to CME and highlighted the gap between CME activity and its recognition and
      funding by employers. They wanted a wide variety of locally based CME activities
      to be recognised, and they valued local activities that linked theory with
      practice. They believed that the college scheme tended to favour academic
      activities over more practical and locally based ones. They found the paired peer
      review process time consuming but valuable for identifying their learning needs
      in some cases, but demonstrated that they have mixed preferences about the way
      they do their CME. CONCLUSIONS: The Wessex pathologists believe that CME is
      important and have positive attitudes to it. Their attitudes to CME echo the
      current literature about what makes CME effective. Unless individuals'
      preferences and difficulties are taken into account, CME programmes in which they
      participate are not likely to succeed.

PMID- 9516885
TI  - Prevalence of six types of human papillomavirus in inverted papilloma and
      papillary transitional cell carcinoma of the bladder: an evaluation by polymerase
      chain reaction.
AB  - AIMS: To study the prevalence of high risk oncogenic human papillomaviruses (HPV)
      in inverted papilloma and papillary transitional cell carcinoma of the bladder.
      METHODS: Ten cases of inverted papilloma and 20 cases of papillary transitional
      cell carcinoma of the bladder from Chinese patients in Hong Kong were examined
      for the presence of HPV type 6, 11, 16, 18, 31, and 33 genomes using the
      polymerase chain reaction and HPV type specific primer probe combinations on
      paraffin wax embedded biopsy specimens. RESULTS: Of the 10 cases of inverted
      papilloma, cases 1 and 6 showed the presence of HPV types 16 and 18,
      respectively. Six of the 20 papillary transitional cell carcinomas were positive
      for HPV type 18. The other HPV types were not detected. CONCLUSIONS: HPV type 18
      was found in 60% and 30% of cases of inverted papilloma and papillary
      transitional cell carcinoma of the bladder, respectively. These tumours were
      rarely associated with HPV types 6, 11, 16, 31, and 33. The role of HPV type 18
      in oncogenesis of inverted papilloma and transitional cell carcinoma of the
      bladder requires further studies.

PMID- 9516887
TI  - Resistance to ciprofloxacin in pathogenic Enterobacteriaceae in England and Wales
      in 1996.
AB  - In 1996, 6% of Escherichia coli from extraintestinal infections were resistant to
      ciprofloxacin with minimum inhibitory concentrations (MICs) > or = 2 mg/l (high
      level resistance). Low level resistance (MIC 0.125-1 mg/l) was also identified in
      7% of Salmonella typhi, 4% of S paratyphi A, and 4% of non-typhoidal salmonellas.
      However, resistance to ciprofloxacin was rarely identified in shigellas. For E
      coli, physicians should be aware that treatment failures may occur when patients
      with invasive illness are treated with ciprofloxacin before the results of
      laboratory sensitivity tests are available. For salmonellas an increasing number
      of treatment failures have been recorded for patients infected with strains with
      low level resistance. Because of the increasing incidence of Enterobacteriaceae
      with low level resistance to ciprofloxacin, it is recommended that for this group
      of organisms a breakpoint of 0.125 mg/l should be included in laboratory
      sensitivity tests.

PMID- 9516888
TI  - Primary epithelioid haemangioendothelioma of the liver: case report and review of
      the literature.
AB  - A 31 year old female patient presented with a one and a half year history of pain
      in the upper abdomen. The pain was mild, constant, dull aching, and increased
      with change in posture or sudden movements. There was no definite relation to
      meals. She also had a lump in the right upper quadrant, which had been gradually
      increasing in size over three months. She had mild anorexia and reported a 5 kg
      weight loss over one year. She had no history of intake of oral contraceptive
      drugs, exposure to vinyl chloride, thorotrast or any other industrial toxin.
      Ultrasonography of the abdomen revealed multiple space occupying lesions of
      altered echotexture in both lobes of the liver. The portal venous system and
      hepatic vascular system were normal. Computed tomography of the abdomen confirmed
      the ultrasound findings. Histopathology was diagnostic for primary epithelioid
      haemangioendothelioma; the first such case reported from India. The patient has
      been put on a waiting list for a liver transplant.

PMID- 9516889
TI  - Cytokeratin 14 as a marker of squamous differentiation in transitional cell
      carcinomas.
AB  - The presence of squamous differentiation in transitional cell carcinomas has been
      variably related to prognosis and response to radiotherapy. This study sought to
      establish whether cytokeratin (CK) 14, normally expressed in the basal cells of
      squamous epithelium, could be used as a reliable marker of the emergence of a
      squamous phenotype in transitional cell carcinomas. In a series of 42 tumours,
      CK14 was expressed in areas of squamous morphology, whereas CK20 identified
      continuing urothelial differentiation. Furthermore, focal positivity for CK14 was
      present in a proportion of tumours with no morphological evidence of squamous
      differentiation, suggesting that it is a more sensitive marker of phenotypic
      switch. Investigation of CK subtypes may be more powerful than morphology alone
      in clinical studies of transitional cell carcinomas as CK expression profiles
      have been related to treatment response in other tumour types.

PMID- 9516890
TI  - A solitary benign lymphoid polyp of the rectum in a 51 year old woman.
AB  - A 51 year old woman presented with rectal bleeding from a mass lying just above
      the dentate line. Multiple biopsies were taken before the diagnosis of a benign
      lymphoid polyp was made. This is a rare condition that more commonly presents in
      children and poses a diagnostic challenge.

PMID- 9516891
TI  - Platelet activating factor revisited.

PMID- 9516892
TI  - Tobacco: the epidemic we could all avoid.

PMID- 9516893
TI  - Enhancement of leukotriene B4 release in stimulated asthmatic neutrophils by
      platelet activating factor.
AB  - BACKGROUND: The role of platelet activating factor (PAF) in asthma remains
      controversial. The priming effect of PAF on leukotriene B4 (LTB4) release, 5
      lipoxygenase activity, and intracellular calcium levels in asthmatic neutrophils
      was examined. METHODS: LTB4 and other lipoxygenase metabolites in neutrophils
      obtained from 17 asthmatic patients and 15 control subjects were measured by
      reverse phase-high performance liquid chromatography (RP-HPLC). Intracellular
      calcium levels were monitored using the fluorescent probe fura-2. RESULTS: The
      mean (SD) basal LTB4, release from neutrophils was not significantly different
      between the two groups (0.05 (0.01) vs 0.03 (0.02) ng/10(6) cells); however, when
      stimulated with calcium ionophore A23187 (2.5 microM), neutrophils from asthma
      patients released more LTB4 than cells from control subjects (15.7 (1.2) vs 9.9
      (1.6) ng/10(6) cells). Although PAF alone did not alter LTB4 release, it enhanced
      the response to subsequent A23187 stimulation. This effect was observed following
      treatment for five minutes with PAF at concentrations > 1.0 microM. The maximal
      effect was seen with 5.0 microM PAF + 2.5 microM A23187 (62.7 (2.2) vs 18.6 (2.3)
      ng/10(6) cells). Pretreatment with PAF also increased 5-lipoxygenase activity and
      intracellular calcium levels in neutrophils from asthmatic patients to a greater
      extent than in those from non-asthmatic patients. CONCLUSIONS: These findings
      indicate that, in neutrophils from asthmatic patients, PAF enhances LTB4 release
      and increases 5-lipoxygenase activity and intracellular calcium to a greater
      extent than in neutrophils from non-asthmatic patients.

PMID- 9516894
TI  - Increased urinary excretion of LTE4 after exercise and attenuation of exercise
      induced bronchospasm by montelukast, a cysteinyl leukotriene receptor antagonist.
AB  - BACKGROUND: A study was undertaken to determine whether montelukast, a new potent
      cysteinyl leukotriene receptor antagonist, attenuates exercise-induced
      bronchoconstriction. The relationship between the urinary excretion of LTE4 and
      exercise-induced bronchoconstriction was also investigated. METHODS: Nineteen non
      smoking asthmatic patients with a forced expiratory volume in one second (FEV1)
      of > or = 65% of the predicted value and a reproducible fall in FEV1 after
      exercise of at least 20% were enrolled. Subjects received placebo and montelukast
      100 mg once daily in the evening or 50 mg twice daily, each for two days, in a
      three-period, randomised, double blind, crossover design. In the evening,
      approximately 20-24 hours after the once daily dose or 12 hours after the twice
      daily dose, a standardised exercise challenge was performed. Data from 14
      patients were available for complete analysis. RESULTS: The mean (SD) maximal
      percentage decrease in FEV1 after exercise was 29.6 (16.0), 17.1 (8.2), and 14.0
      (9.4) for placebo, once daily, and twice daily regimens, respectively. The mean
      (95% CI) percentage protection was 37 (15 to 59) for the group who received 50 mg
      twice daily and 50 (31 to 69) for those who received 100 mg once daily. Active
      treatments were not different from each other. The mean (SD) plasma
      concentrations of montelukast were higher after the twice daily regimen (1.27
      (0.81) microgram/ml) than after the once daily regimen (0.12 (0.09)
      microgram/ml); there was no correlation between the percentage protection against
      exercise-induced bronchoconstriction and plasma concentrations. After exercise
      urinary excretion of LTE4 increased significantly during placebo treatment (from
      34.3 to 73.7 pg/mg creatinine; p < 0.05) but did not correlate with the extent of
      exercise-induced bronchoconstriction. CONCLUSIONS: Montelukast protects similarly
      against exercise-induced bronchoconstriction between plasma concentrations of
      0.12 and 1.27 micrograms/ml. The increase in the urinary excretion of LTE4 after
      exercise and the protection from exercise-induced bronchoconstriction with a
      cysteinyl leukotriene receptor antagonist provide further evidence of the role of
      leukotrienes in the pathogenesis of exercise-induced bronchoconstriction.

PMID- 9516895
TI  - Effects of airway calibre on lung delivery of nebulised salbutamol.
AB  - BACKGROUND: A study was undertaken to test the hypothesis that airway calibre may
      alter lung deposition and therefore lung bioavailability of inhaled drugs as a
      result of narrowed airways reducing peripheral drug delivery. This was evaluated
      using the early lung absorption profile of salbutamol over the first 30 minutes
      after inhalation. METHODS: Three groups were compared: (1) 10 normal subjects
      with mean forced expiratory volume in one second (FEV1) 109.5% predicted and mid
      forced expiratory flow (FEF25-75) 103.0%, (2) 10 mild asthmatic patients with
      FEV1 102.0% and FEF25-75 82.6%, and (3) 10 severe asthmatic patients with FEV1
      49.2% and FEF25-75 27.5% predicted. Each subject had one study visit where a
      single dose of nebulised salbutamol was given (40 micrograms/kg) via a Ventstream
      nebuliser with mouthpiece followed by mouth rinsing. Plasma salbutamol levels
      were measured at five, 10, 20, and 30 minutes after the end of nebulisation with
      calculation of maximal (Cmax) and average (Cav) concentration over 0-30 minutes.
      Systemic beta 2 responses (plasma potassium, tremor and heart rate) and airway
      responses (FEV1, FEF25-75) were measured before and 30 minutes after
      nebulisation. RESULTS: For Cav over 0-30 minutes the severe asthmatic patients
      had a lower plasma salbutamol concentration (1.31 ng/ml) than either the normal
      subjects (2.40 ng/ml) or those with mild asthma (2.45 ng/ml): normal subjects
      versus severe asthmatics 95% CI 0.30 to 1.88, mild versus severe asthmatics 95%
      CI 0.07 to 2.21. Airway responses as delta FEF25-75 were lower in the severe
      asthmatic subjects (0.30 l/s) than in either the normal subjects (0.69 l/s) or
      those with mild asthma (0.74 l/s): normal subjects versus severe asthmatic
      subjects 95% CI 0.09 to 0.88, mild versus severe asthmatics 95% CI 0.04 to 0.93.
      Values for delta log tremor also showed attenuated responses in those with severe
      asthma (1.22 mg2/s) compared with normal subjects (2.00 mg2/s) or those with mild
      asthma (2.02 mg2/s): normal subjects versus those with severe asthma 95% CI -0.02
      to 3.30, mild versus severe asthmatics 95% CI 0.02 to 3.30. CONCLUSIONS: These
      results show that baseline airway calibre significantly alters the early lung
      absorption profile of salbutamol in patients with severe asthma. This may have
      implications in terms of optimising dose and delivery of inhaled beta 2 agonists
      in these patients.

PMID- 9516896
TI  - Respiratory effects of air pollution in chronic obstructive pulmonary disease: a
      three month prospective study.
AB  - BACKGROUND: A study was undertaken to investigate the relationship between air
      pollution levels and respiratory symptoms and peak expiratory flow rate (PEFR) in
      subjects with chronic obstructive pulmonary disease (COPD) living in
      Christchurch, New Zealand. METHODS: Forty subjects aged over 55 years with COPD
      completed twice daily diaries for three months during the winter of 1994.
      Subjects recorded respiratory symptoms, PEFR, outdoor activity, visits to doctor
      or hospital, and medication use. All were resident within a 5 km radius of the
      regional council's air pollution monitoring site. Daily and hourly mean pollutant
      levels (particulates (PM10, nitrogen dioxide (NO2), sulphur dioxide (SO2) and
      carbon monoxide (CO)) were measured at the monitoring site. RESULTS: Pollution
      levels were generally low relative to those recorded in previous years. The New
      Zealand Ministry for the Environment guidelines for PM10 were exceeded on five
      occasions, and for CO six times. No association was found between PEFR and any of
      the pollution variables. A rise in the PM10 concentration equivalent to the
      interquartile range was associated with an increase in night time chest symptoms
      (relative risk 1.38, 95% CI 1.07 to 1.78). A rise in NO2 concentrations
      equivalent to the interquartile range was associated with increased reliever
      inhaler use (relative risk 1.42, 95% CI 1.13 to 1.79) and for 24 hour lag
      analysis with increased nebuliser use (relative risk 2.81, 95% CI 1.81 to 4.39).
      There was no increase in the relative risk of other symptoms in relation to
      pollution levels. CONCLUSIONS: These effects, demonstrated in a small susceptible
      group of subjects with COPD, indicate that adverse outcomes can be measured in
      response to pollution levels that are within current guidelines.

PMID- 9516897
TI  - Relationship of serum elastin peptide level to single breath transfer factor for
      carbon monoxide in French coal miners.
AB  - BACKGROUND: Clinical and epidemiological studies have given discordant results on
      the usefulness of the level of circulating elastin peptide (EP), a potential
      marker of both elastin destruction (a key phenomenon in pulmonary emphysema) and
      neosynthesis, for assessing structural changes in the lung extracellular matrix.
      The aim of the present study was to explore the relationship between levels of EP
      and forced expiratory volume in one second (FEV1) and single breath transfer
      factor for carbon monoxide (TLCO and KCO) in coal miners. METHODS: The study
      population comprised 227 working coal miners aged 34-50 years consisting of 75
      miners heavily exposed to underground coal dust with pulmonary radiographs
      classified as 0/1 or 1/0 by the International Labour Office classification, 75
      exposed miners with radiographs classified as normal (0/0), and 77 miners
      slightly exposed to coal dust with normal radiographs. The subjects answered a
      standardised questionnaire and performed spirometric tests and a carbon monoxide
      (CO) transfer test. RESULTS: No association was observed between EP levels and %
      predicted FEV1 (or FEV1/FVC). The level of EP increased significantly with
      decreased % predicted TLCO (r = -0.20). Miners in the lowest % predicted KCO
      quintile had higher EP levels than the rest (3.28 (1.37) vs 2.47 (1.16)). A
      significantly lower EP level was observed in miners with radiographs classified
      as 1/0 or 0/1, especially in those with round opacities, compared with miners
      with a normal radiograph, and in current smokers compared with the rest.
      CONCLUSIONS: The results of this study suggest that the level of EP may reflect
      some remodelling activity in emphysema and lung fibrosis.

PMID- 9516898
TI  - Decreased nitric oxide in the exhaled air of patients with systemic sclerosis
      with pulmonary hypertension.
AB  - BACKGROUND: Systemic sclerosis (SSc) may be complicated by pulmonary hypertension
      (PHT), which can occur both in the setting of fibrosing alveolitis or as lone
      pulmonary vascular disease. Nitric oxide (NO) is a powerful vasodilator and is
      produced by various cells in the respiratory tract including pulmonary vascular
      endothelial cells and can be measured in expired air. A study was undertaken to
      test the hypothesis that exhaled NO levels would be decreased in patients with
      SSc with PHT and to assess the utility of this measurement in discriminating
      between patients with and without PHT, regardless of concurrent fibrosing
      alveolitis. METHODS: Exhaled NO was measured with a chemiluminescence analyser in
      23 patients with SSc (six with PHT, 17 subjects without) and in 67 normal
      individuals. Doppler echocardiography was used to assess pulmonary artery
      pressure in subjects with SSc, and lung function tests were performed at the same
      visit as NO measurements. Thin section CT scans were analysed for the presence of
      abnormality consistent with fibrosing alveolitis. RESULTS: Patients with SSc with
      PHT had a greater reduction in arterial oxygen tension (PaO2) and carbon monoxide
      gas transfer (TLCO) than patients with SSc without PHT. Exhaled NO was
      significantly higher in patients with SSc without PHT than in normal individuals,
      and was significantly decreased in patients with SSc with PHT (mean (SD) 20 (6)
      ppb) compared with 149 (19) ppb in those with SSc without PHT (mean difference
      129 (95% CI 112 to 146) ppb) and 80 (7) ppb in normal individuals (mean
      difference 60 (95% CI 54 to 66) ppb). CONCLUSION: Exhaled NO is decreased in
      patients with SSc with PHT compared with both normal individuals and patients
      with SSc without PHT.

PMID- 9516899
TI  - Role of heat shock proteins in the pathogenesis of cystic fibrosis arthritis.
AB  - BACKGROUND: Arthritis is a well recognised complication of cystic fibrosis. The
      cause of this arthritis is not yet clear but it is likely to be an immunological
      reaction to one of the many bacterial antigens to which the lungs are exposed.
      One such group, the heat shock proteins, (hsp), was investigated. These are
      immunodominant antigens of a wide variety of infectious microorganisms and have
      varying amino acid chain sequences, some of which are similar to those found in
      human tissues. METHODS: Antibodies to human hsp 27 and hsp 90 in the serum of
      patients with cystic fibrosis, with and without arthritis, and in normal age and
      sex matched healthy controls were measured. The severity of the cystic fibrosis
      was assessed by lung function tests and chest radiographs. The nature of the
      organisms colonising the lungs was determined by bacteriological examination of
      sputum. RESULTS: Higher mean titres of serum IgG anti-human hsp 27 and hsp 90
      antibodies were found in 50 patients with cystic fibrosis than in healthy
      controls (hsp 27, 0.25 (95% CI 0.19 to 0.33) versus 0.05 (95% CI 0.04 to 0.07);
      hsp 90, 0.27 (95% CI 0.22 to 0.32) versus 0.11 (95% CI 0.08 to 0.14)). These
      antibodies were higher in patients in whom the lungs were colonised with
      Pseudomonas aeruginosa than in those without infection (hsp 27, 0.41 (95% CI 0.17
      to 0.63) versus 0.18 (95% CI 0.10 to 0.27); hsp 90, 0.37 (95% CI 0.18 to 0.57)
      versus 0.22 (95% CI 0.16 to 0.29)). The eight patients with cystic fibrosis with
      arthritis had higher anti-hsp 27 antibodies (0.48 (95% CI 0.13 to 0.92)) than the
      42 patients without arthritis (0.22 (95% CI 0.17 to 0.30)). CONCLUSIONS: These
      findings suggest that the arthritis associated with cystic fibrosis, despite
      being seronegative for rheumatoid factor, was associated with more severe lung
      disease and with a greater inflammatory response to heat shock proteins.

PMID- 9516900
TI  - Tuberculosis in England and Wales in 1993: results of a national survey. Public
      Health Laboratory Service/British Thoracic Society/Department of Health
      Collaborative Group.
AB  - BACKGROUND: A national survey of tuberculosis notifications in England and Wales
      was carried out in 1993 to determine the notification rate of tuberculosis and
      the trends in the occurrence of disease by ethnic group in comparison with the
      findings of similar surveys in 1978/79, 1983, and 1988. The prevalence of HIV
      infection in adults notified with tuberculosis in the survey period was also
      estimated. METHODS: Clinical, bacteriological, and sociodemographic information
      was obtained on all newly notified cases of tuberculosis in England and Wales
      during the six months from 2 January to 2 July 1993. The prevalence of HIV
      infection in 16-54 year old patients with tuberculosis notified throughout 1993
      was assessed using "unlinked anonymous" testing supplemented by matching of the
      register of patients with tuberculosis with that of patients with AIDS reported
      to the PHLS AIDS centre. Annual notification rates were calculated using
      population estimates from the 1993 Labour Force Survey. RESULTS: A total of 2706
      newly notified patients was eligible for inclusion in the survey of whom 2458
      were previously untreated the comparable figures for 1988 were 2408 and 2163. The
      number of patients of white ethnic origin decreased from 1142 (53%) in 1988 to
      1088 (44%) in 1993 whereas those of patients of Indian, Pakistani, or Bangladeshi
      (Indian subcontinent (ISC)) ethnic origin increased from 843 (39%) in 1988 to
      1014 (41%) and those of "other" (non-white, non-ISC) ethnic origins increased
      from 178 (8%) to 356 (14%). The largest increase was seen in the black African
      ethnic group from 37 in 1988 to 171 in 1993. Forty nine per cent of patients had
      been born abroad and the highest rates were seen in those who had recently
      arrived in this country. The overall annual notification rate for previously
      untreated tuberculosis in England and Wales increased between 1988 and 1993 from
      8.4 to 9.2 per 100,000 population. The rate declined in the white, Indian, and
      black Caribbean ethnic groups and increased in all other groups. In the white
      group the rate of decline has slowed since the last survey: in several age groups
      the rates were higher in 1993 than 1988 but the numbers in these groups were
      small. Thirty six (4.1%) of the 882 previously untreated respiratory cases were
      resistant to isoniazid and three (0.3%) to isoniazid and rifampicin. Sixty two
      (2.3%) adults aged 16-54 years were estimated to be HIV-infected. Evidence of
      under-reporting of HIV positive tuberculosis patients was found. CONCLUSIONS: The
      number of cases and annual notification rate for previously untreated
      tuberculosis increased between 1988 and 1993. Although the decline in rates in
      the white population has continued, the rate of decline has slowed. The high
      rates in the ISC ethnic group population have continued to decline since 1988
      whereas rates in the black African group have increased. An increased proportion
      of cases were found among people born abroad, particularly those recently arrived
      in this country. In previously untreated cases the level of drug resistance
      remains low and multi-drug resistance is rare. A small proportion of adults with
      tuberculosis were infected with HIV but there may be selective undernotification
      of tuberculosis in these patients.

PMID- 9516901
TI  - Use of home sleep studies for diagnosis of the sleep apnoea/hypopnoea syndrome.
AB  - BACKGROUND: A study was undertaken to test the hypothesis that unsupervised
      domiciliary limited sleep studies do not impair the accuracy of diagnosis when
      used to investigate the sleep apnoea/hypopnoea syndrome (SAHS) and can be cheaper
      than laboratory polysomnography. METHODS: For validation, 23 subjects with
      suspected SAHS underwent laboratory polysomnography and a home study (EdenTec
      3711) on successive nights. All subjects with > 15 apnoeas + hypopnoeas (A +
      H)/hour on polysomnography showed > 30 A + H/hour on their home study.
      Thereafter, in a prospective trial 150 subjects had a home study as the initial
      investigation and studies showing > 30 events/hour were regarded as diagnostic of
      SAHS. Those showing fewer events were investigated with polysomnography if
      necessary. Time to treatment, outcome, and costs of this protocol were compared
      with those of 75 patients investigated initially with polysomnography. RESULTS:
      Of the prospective trial subjects, 29% had > 30 A + H/hour and proceeded directly
      from home study to treatment; 15% without daytime sleepiness were not
      investigated further. Polysomnography was undertaken to establish a diagnosis in
      56% of cases, including 18% whose home studies were unsuccessful. Compared with
      the 75 control patients, this protocol gave a diagnosis faster (median 18 (range
      0-221) versus 47 (0-227) days, p < 0.001) and more cheaply (mean (SD) 164 pounds
      (104) versus 210 pounds (0), p < 0.001). The proportions offered CPAP (61% versus
      67%) and subsequent objective CPAP usage (mean 4.7 (2.4) versus 5.0 (2.4)
      hours/night) were not different. CONCLUSIONS: Use of home sleep studies has
      benefits in time and cost. For diagnostic reliability a further sleep study was
      required in 56% of cases.

PMID- 9516902
TI  - Effect of a novel 5-lipoxygenase activating protein inhibitor, BAYx 1005, on
      asthma induced by cold dry air.
AB  - BACKGROUND: Leukotrienes have been implicated in the mediation of airway
      obstruction induced by hyperventilation of cold dry air in asthmatic subjects.
      The effect of a novel inhibitor of 5-lipoxygenase activating protein, BAYx 1005,
      on the bronchospastic response to cold dry air hyperventilation was investigated
      in asthmatic patients. METHODS: After a screening cold dry air hyperventilation
      challenge to document cold air responsiveness, 16 asthmatic subjects (baseline
      forced expiratory volume in one second (FEV1) > 60% of predicted) underwent cold
      air challenge three hours after receiving 750 mg of BAYx 1005 or placebo using a
      randomised, double blind, crossover design. Leukotriene synthesis inhibition was
      estimated by measuring the concentration of leukotriene B4 in whole blood
      stimulated with calcium ionophore A21387. RESULTS: Treatment with BAYx 1005
      produced a 34% (95% CI 11 to 63) increase in the amount of cold air minute
      ventilation required for a 10% decrease in FEV1 (PD10VE) compared with placebo
      (mean (SE) 37.6 (1.12) 1/min compared with 28.0 (1.13) 1/min, p < 0.006). The
      PD20VE increased 19% (95% CI 8 to 31) after treatment with BAYx 1005 compared
      with placebo (57.3(1.10)1/min versus 48.1 (1.10) 1/min, p < 0.002). Treatment
      with BAYx 1005 produced a 15.4% decrease in ionophore-stimulated LTB4 production,
      while treatment with placebo produced a 7.1% increase in ex vivo LTB4 (p < 0.02).
      CONCLUSIONS: Treatment with BAYx 1005, a novel inhibitor of leukotriene
      synthesis, produced a significant blunting of cold dry air responsiveness
      consistent with the hypothesis that leukotrienes mediate part of the
      bronchoconstriction induced by hyperventilation of cold dry air.

PMID- 9516903
TI  - Lymphocyte dynamics: caution in interpreting BAL numbers.
AB  - In various allergic and inflammatory lung diseases the number and subset
      composition of lymphocytes in the bronchoalveolar lavage (BAL) fluid are taken as
      indicators of the state of the disease. The number of lymphocytes in the BAL
      fluid depends on three main parameters: (1) entry into the bronchoalveolar space
      from the different compartments of the lung, (2) persistence in the
      bronchoalveolar space which is modified by the rate of local proliferation and
      apoptosis, and (3) exit into the draining bronchial lymph node via the lymphatic
      system. In healthy individuals lymphocytes in the BAL fluid seem to be a stable
      pool: each day there is hardly any entry, local cell division or cell death and
      few lymphocytes emigrate from this compartment. In contrast, during inflammatory,
      toxic and allergic reactions all parameters can increase rapidly with more
      lymphocytes entering, proliferating and/or undergoing apoptosis locally. Very
      little is known about factors such as cytokines and chemokines which may regulate
      these parameters. When interpreting data on lymphocyte numbers in patients,
      lymphocyte dynamics in the bronchoalveolar space have to be considered, and in
      the future it may be possible to manipulate these lymphocyte fluxes for
      therapeutic purposes.

PMID- 9516904
TI  - Health effects of passive smoking. 3. Parental smoking and prevalence of
      respiratory symptoms and asthma in school age children.
AB  - BACKGROUND: A systematic quantitative review of the evidence relating parental
      smoking to the prevalence of asthma and respiratory symptoms was conducted
      amongst school age children. METHODS: Sixty relevant studies were identified
      after consideration of 1593 articles selected by electronic search of the Embase
      and Medline databases using keywords relevant to passive smoking in children. The
      search was completed in April 1997 and identified 25 studies of asthma, 41 of
      wheeze, 34 of chronic cough, seven of chronic phlegm and six of breathlessness
      which were included in a quantitative overview. RESULTS: The pooled odds ratios
      for either parent smoking were 1.21 (95% CI 1.10 to 1.34) for asthma, 1.24 (95%
      CI 1.17 to 1.31) for wheeze, 1.40 (95% CI 1.27 to 1.53) for cough, 1.35 (95% CI
      1.13 to 1.62) for phlegm, and 1.31 (95% CI 1.08 to 1.59) for breathlessness.
      Adjustment for confounding had little effect. Evidence of heterogeneity between
      studies appeared largely explicable by publication bias with a superfluity of
      small studies with large odds ratios. However, excluding these had little effect
      on the pooled odds ratios. The prevalence of all symptoms increased with the
      number of parents who smoked. While maternal smoking had a greater effect than
      paternal smoking, the effect of father only was clearly significant. CONCLUSIONS:
      The relationship between parental smoking and respiratory symptoms seems very
      likely to be causal given statistical significance, robustness to adjustment for
      confounding factors, consistency of the findings in different countries, and
      evidence of dose response. The raised risk in households where the father, but
      not the mother, smoked argues for a postnatal effect.

PMID- 9516905
TI  - Recurrent post-partum pulmonary eosinophilia.
AB  - In 1980 a 23 year old woman developed idiopathic eosinophilic pneumonia which was
      successfully treated with corticosteroids. She subsequently developed two
      identical relapses in the post-partum period.

PMID- 9516906
TI  - Pericardial effusion associated with asbestos exposure.
AB  - The case history is presented of a 60 year old man who developed a pericardial
      effusion. Chest radiography showed pleural thickening and calcification.
      Pericardiotomy was performed and revealed nonspecific inflammatory lesions.
      Occupational exposure to asbestos and exclusion of other causes led to the
      diagnosis of benign asbestos pericardial effusion.

PMID- 9516907
TI  - Montelukast (MK-0476)

PMID- 9516908
TI  - Treatment of pleural empyema.

PMID- 9516909
TI  - Endothelial cell vehicles for delivery of cytotoxic genes as a gene therapy
      approach for carcinoma of the ovary.
AB  - Human umbilical vein endothelial cells (HUVECs) were evaluated for utility as a
      vector to achieve a bystander effect and killing of ovarian carcinoma cell lines.
      After demonstrating that HUVECs could be transduced with the reporter gene LacZ
      encoded by an adenoviral vector, appropriate cell killing of the AdCMVHSV-TK
      transduced HUVECs was exhibited after treatment with 20 microM ganciclovir.
      Mixing experiments were then performed to determine whether the transduced HUVECs
      would demonstrate a bystander effect with the ovarian cancer cell lines. When 50%
      AdCMVHSV-TK-transduced HUVECs were mixed with untransduced ovarian cancer cells,
      > 70% of all cells were killed. Finally, s.c. and i.p. injections of herpes
      simplex-thymidine kinase-expressing HUVECs and SKOV3ip1 tumor cells were
      performed to evaluate the effects of HUVECs in in vivo models. These studies
      showed a decrease in tumor growth s.c. as well as a statistically significant
      survival prolongation (P < 0.05) in the i.p. model. These findings suggest that
      endothelial cells may be used as a vehicle for the delivery of cytotoxicity
      (bystander effect) in molecular chemotherapy.

PMID- 9516910
TI  - A prospective study of K-ras mutations in the plasma of pancreatic cancer
      patients.
AB  - K-ras mutations are frequently found in primary pancreatic adenocarcinomas. In
      this prospective study, we looked for K-ras mutations in the plasma of patients
      with pancreatic cancer. We isolated plasma DNA from 21 pancreatic cancer patients
      using a simple and rapid extraction technique and detected K-ras alterations with
      a PCR assay and subsequent product sequencing. Patients were followed up to
      determine their clinical outcome. We found K-ras mutations in the plasma of 17
      patients (81%). In cases in which both plasma and pancreatic tissue were
      available, DNA mutations were similar in corresponding plasma and tissue samples.
      Plasma DNA alterations were found 5-14 months before clinical diagnosis in four
      patients. Mutant DNA was not found in the plasma of two patients with chronic
      pancreatitis or in five healthy controls. Our results indicate that K-ras
      mutations are often found in DNA isolated from the plasma of pancreatic cancer
      patients and that a noninvasive plasma-based assay may provide qualitative
      diagnostic information to clinicians in the future. Larger studies are required
      to further assess the relevance of our findings to clinical practice.

PMID- 9516911
TI  - Pharmacodynamics of doxorubicin in human prostate tumors.
AB  - The pharmacodynamics of doxorubicin in human prostate tumors were studied using
      histocultures of radical prostatectomy specimens. Drug treatment lasted 96 h. The
      antiproliferative effect was measured by the inhibition of DNA precursor
      ([3H]thymidine) incorporation, and the cytotoxic effect was measured by
      monitoring cells with fragmented DNA, as indicated by the terminal
      deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay. The average
      [3H]thymidine labeling index in 17 tumors was 39% (range, 20-56%). The
      antiproliferative and cytotoxic effects were concentration dependent and reached
      100% at 6 and 17 microM doxorubicin. The cytotoxic concentrations were
      significantly higher than the antiproliferative concentrations, indicating that
      prostate tumors were more sensitive to the antiproliferative effect than they
      were to the cytotoxic effect of doxorubicin. The antiproliferative effect was
      inversely correlated with patient's age (P < 0.02) and weakly correlated with LI
      and Gleason grade (P = 0.07 and 0.06, respectively), but it was not correlated
      with clinical stage, prostate-specific antigen secretion, or race of patients (P
      > 0.12). In contrast, the cytotoxic effect was positively correlated with Gleason
      grade (P < 0.05) and weakly correlated with stage (P < 0.08), but it was not
      correlated with the other parameters (P > 0.18). The opposite correlations
      between the two effects with tumor grade suggest that the two effects are not
      coupled. A comparison of the drug concentrations required to produce 50%
      antiproliferative (0.06 microM) and cytotoxic (2 microM) effects and the
      literature data on plasma drug concentrations derived from systemic treatment
      suggest that there are minimal drug effects at the clinically achievable drug
      concentrations and that regional delivery of doxorubicin to the prostate may be
      necessary to provide adequate concentrations to produce antiproliferative and
      cytotoxic effects.

PMID- 9516912
TI  - Phase II trial of sequential radiation and interleukin 2 in the treatment of
      patients with metastatic renal cell carcinoma.
AB  - We have previously demonstrated that local tumor irradiation effectively enhanced
      the therapeutic effect of interleukin 2 (IL-2) therapy in an experimental murine
      renal adenocarcinoma model. Based on these preclinical studies, we have designed
      and initiated a Phase II trial of irradiation combined with IL-2 for the
      treatment of metastatic renal cell carcinoma. Patients received 800 cGy to the
      primary or metastatic lesions on days 1 and 15 followed by IL-2 (600,000 IU/kg
      i.v.) every 8 h on days 4-8 and 18-22. Sixteen patients were entered; all
      completed treatment and are therefore evaluable for toxicity and response. Two
      partial remissions were seen for a response rate of 12.5% (95% confidence
      interval, 0-28.7). There was no increase in toxicity over that which is
      anticipated from IL-2 alone. The antitumor activity seen in this trial is
      consistent with what would be expected from high-dose IL-2 alone.

PMID- 9516915
TI  - Phase I dose de-escalation trial of alpha-difluoromethylornithine in patients
      with grade 3 cervical intraepithelial neoplasia.
AB  - alpha-Difluoromethylornithine (DFMO) is a suicide inhibitor of ornithine
      decarboxylase and potent antiproliferative chemopreventive agent. We conducted a
      dose de-escalation Phase I trial of DFMO in patients with grade 3 cervical
      intraepithelial neoplasia to determine an optimal dose of DFMO using ornithine
      decarboxylase activity and polyamine modulation as surrogate biomarkers and to
      evaluate its toxicity. Thirty patients with biopsy-confirmed grade 3 cervical
      intraepithelial neoplasia were assigned sequentially to one of five DFMO doses
      (1.000, 0.500, 0.250, 0.125, or 0.060 g/m2) given daily for 31 days. One patient
      was excluded from analysis for protocol violation. Polyamine levels were assessed
      in cervical tissue, plasma, and RBCs. Tissue and blood samples were obtained
      before and after treatment with DFMO. All patients underwent loop excision of the
      cervix at the end of the study for complete histological evaluation and
      definitive treatment of the premalignant condition. No major clinical toxicity
      was observed at any DFMO dose. A reduction in tissue spermidine to spermine
      (SPD:SPM) ratio and an increase in plasma arginine levels were observed among
      patients receiving 1.000 g/m2/day (P < 0.05). A nonsignificant reduction in
      SPD:SPM ratio was also observed in the 0.500 g/m2/day dose group, and a
      nonsignificant increase in plasma arginine level was observed down to the 0.125
      g/m2/day dose level. There was no evidence of modulation of other polyamines or
      precursors. Fifteen patients experienced a complete (5 patients) or partial (10
      patients) histological response. In conclusion, DFMO was well tolerated and
      significantly modulated tissue SPD:SPM ratio and plasma arginine level at the
      dose of 1.000 g/m2/day. To clarify whether DFMO has activity at lower doses,
      these results will be tested in a three-armed double-blinded Phase II study using
      placebo and DFMO doses of 0.500 and 0.125 g/m2/day.

PMID- 9516914
TI  - Expression of potential target antigens for immunotherapy on primary and
      metastatic prostate cancers.
AB  - Defining the expression of tumor-associated antigens on primary and metastatic
      prostate cancer is the crucial first step in selecting appropriate targets for
      immune attack. In this study, the distribution of the tumor-associated antigens
      GM2, Tn, sTn, Thompson-Friedenreich antigen (TF), Globo H, Le(y), MUC1, MUC2,
      MUC3, MUC4, MUC5AC, MUC5B, MUC7, carcinoembryonic antigen, beta chain of human
      chorionic gonadotropin (hCG beta), HER2/neu, PSMA, and KSA on primary and
      metastatic prostate cancer and 16 types of normal tissues was compared by
      immunohistochemistry, using a panel of well-characterized monoclonal antibodies.
      Our results show that GM2, KSA, and MUC2 were strongly expressed on 8 or 9 of 9
      metastatic prostate cancer biopsy specimens and, with PSMA, hCG beta, TF, Tn, and
      sTn, on 8 or more of 11 primary prostate cancer specimens. Tn, MUC1, and PSMA
      were expressed on 4-6 of 9 metastatic specimens. The remaining antigens were
      expressed on no more than three of nine metastatic specimens. Normal tissues were
      also tested with all antibodies. With regard to the eight antigens most widely
      expressed on prostate cancers, PSMA was not expressed significantly on any of the
      normal tissues except prostate epithelium. Tn, sTn, hCG beta, and MUC2 were
      detected on up to 3 of 10 types of normal epithelia. GM2, TF, MUC1, and KSA were
      more broadly distributed on normal epithelia, all primarily at the secretory
      borders. STn, KSA, and hCG beta were also detected in the testis, and GM2 was
      expressed on gray matter of brain. From the 30 antigens that we have screened,
      this study provides the basis for selecting GM2, TF, Tn, sTn, hCG beta, MUC1,
      MUC2, KSA, and PSMA as target antigens for specific immunotherapy of prostate
      cancer.

PMID- 9516913
TI  - RET/PTC oncogene activation defines a subset of papillary thyroid carcinomas
      lacking evidence of progression to poorly differentiated or undifferentiated
      tumor phenotypes.
AB  - Malignant tumors of the thyroid gland vary considerably in aggressiveness,
      ranging from a well-differentiated, clinically indolent, to an undifferentiated,
      often lethal phenotype. Undifferentiated (anaplastic) thyroid tumors are supposed
      to be derived, through a process of progression, from previously differentiated
      neoplasms. A common genetic alteration in thyroid tumors is the rearrangement of
      the tyrosine kinase-encoding RET proto-oncogene, leading to the generation of
      chimeric RET/PTC oncogenes. To define the characteristics of the thyroid tumor
      subset with RET rearrangements, we have investigated its activation by a combined
      immunohistochemistry and reverse transcription-PCR approach in a series of 316
      well-characterized thyroid tumors representative of the main diagnostic groups.
      RET activation was detected in 81 of 201 (40.3%) papillary carcinomas. It
      correlated with tumors exhibiting the "classic" morphological features of
      papillary cancer or with the microcarcinoma subtype (P = 0.017). RET activation
      in papillary carcinoma was not associated with clinical markers (such as large
      tumor size, extrathyroidal extension, or metastases) of increased morbidity.
      Follicular-type neoplasms (61 adenomas and 22 carcinomas), as well as the
      aggressive poorly differentiated (15 cases) or undifferentiated (anaplastic)
      carcinomas (17 cases), were negative. This study demonstrates that all thyroid
      carcinomas harboring activating RET rearrangements exhibit a well-differentiated
      phenotype, that of papillary carcinoma, and indicates that the subset of RET/PTC
      positive papillary carcinomas do not progress to more aggressive, less
      differentiated tumor phenotypes.

PMID- 9516916
TI  - Factors affecting mobilization of peripheral blood progenitor cells in patients
      with lymphoma.
AB  - The objective of this study was to identify factors associated with poor
      mobilization of peripheral blood progenitor cells (PBPCs) or delayed platelet
      engraftment after high-dose therapy and autologous stem cell transplantation in
      patients with lymphoma. Fifty-eight patients with Hodgkin's disease or non
      Hodgkin's lymphoma underwent PBPC transplantation as the "best available therapy"
      at Memorial Sloan-Kettering Cancer Center (New York, NY) between 1993 and 1995.
      PBPCs were mobilized with either granulocyte colony-stimulating factor (G-CSF)
      alone (n = 19) or G-CSF following combination chemotherapy (n = 39). Forty-eight
      of these patients underwent a PBPC transplant, receiving a conditioning regimen
      containing cyclophosphamide, etoposide, and either total body irradiation, total
      lymphoid irradiation, or carmustine. A median number of 4.6 x 10(6) CD34+
      cells/kg were obtained with a median of three leukapheresis procedures.
      Mobilization of PBPCs using chemotherapy plus G-CSF was superior to G-CSF alone
      (6.7 x 10(6) versus 1.5 x 10(6) CD34+ cells/kg; P = 0.0002). Poorer mobilization
      of progenitor cells was observed in patients who had previously received stem
      cell-toxic chemotherapy, including (a) nitrogen mustard, procarbazine, melphalan,
      carmustine or > 7.5 g of cytarabine chemotherapy premobilization (2.0 x 10(6)
      versus 6.0 x 10(6) CD34+ cells/kg; P = 0.005), or (b) > or = 11 cycles of any
      previous chemotherapy (2.6 x 10(6) versus 6.7 x 10(6) CD34+ cells/kg; P = 0.02).
      Platelet recovery to > 20,000/microliter was delayed in patients who received <
      2.0 x 10(6) CD34+ cells (median, 13 versus 22 days; P = 0.06). Patients who
      received > or = 11 cycles of chemotherapy prior to PBPC mobilization tended to
      have delayed platelet recovery to > 20,000/microliter and to require more
      platelet transfusions than less extensively pretreated patients (median, 13.5
      versus 23.5 days; P = 0.15; median number of platelet transfusion episodes, 13
      versus 9; P = 0.17). These data suggest that current strategies to mobilize PBPCs
      may be suboptimal in patients who have received either stem cell-toxic
      chemotherapy or > or = 11 cycles of chemotherapy prior to PBPC mobilization.
      Alternative approaches, such as ex vivo expansion or the use of other growth
      factors in addition to G-CSF, may improve mobilization of progenitor cells for
      PBPC transplantation.

PMID- 9516917
TI  - Phase I trial of the colloidal dispersion formulation of 9-amino-20(S)
      camptothecin administered as a 72-hour continuous intravenous infusion.
AB  - The camptothecins are a class of potent cytotoxic anticancer agents that interact
      with the nuclear enzyme topoisomerase I to produce lethal DNA strand cleavages. 9
      Amino-20(S)-camptothecin (9AC) was introduced into Phase I clinical trials in
      dimethylacetamide and polyethylene glycol 400 in a 10 mM phosphoric acid vehicle
      for i.v. solubility. A lyophilized colloidal dispersion (CD) of 9AC for
      reconstitution with 20% dextrose in normal saline was developed as an alternative
      formulation. Patients (ages 25-75 years) with normal liver and kidney function,
      Eastern Cooperative Oncology Group performance status < or = 2, and up to two
      prior chemotherapy regimens were treated. The initial infusion rate was 37.5
      micrograms/m2/h as a 72-h continuous infusion (2.7 mg/m2 total dose). Patient
      cohorts were treated with escalating infusion rates until grade 4 hematological
      or other grade 3 toxicity developed. Pharmacokinetic sampling was performed on
      all patients, and 9AC lactone concentrations in plasma were determined by a high
      performance liquid chromatographic assay. Twenty-five patients received a total
      of 65 courses of 9AC CD at doses from 2.70 to 4.65 mg/m2. The dose-limiting
      toxicity was neutropenia, with little nonhematological toxicity. Nonlinear
      regression analysis of pooled patient data yielded a total plasma clearance of
      30.3 +/- 4.5 liters/h/m2, a half-life of 22.5 +/- 8.5 h, a mean residence time of
      9.7 +/- 3.5 h, and a steady-state volume of distribution of 325 +/- 145
      liters/m2. Although no objective responses were seen, 9 of 25 patients exhibited
      stable disease for 2-6 months. The plasma pharmacokinetics of 9AC lactone in
      cancer patients were comparable between the 9AC CD and soluble formulations. The
      dosing regimen recommended for Phase II trials of the 9AC CD formulation is 54.2
      micrograms/m2/h, given as a 72-h continuous i.v. infusion every 3 weeks.

PMID- 9516918
TI  - Decreased dihydropyrimidine dehydrogenase activity in a population of patients
      with breast cancer: implication for 5-fluorouracil-based chemotherapy.
AB  - Dihydropyrimidine dehydrogenase (DPD) is the initial, rate-limiting enzyme in the
      catabolism of 5-fluorouracil (5-FU), one of the most widely used chemotherapeutic
      agents in the treatment of breast cancer. The objective of this study was to
      determine the population characteristics of DPD activity in patients with breast
      cancer as well as the frequency of DPD deficiency in this population. DPD
      activity in peripheral blood mononuclear cells (PBM-DPD) was determined in 360
      patients with breast cancer, with the mean PBM-DPD (0.26 +/- 0.01 nmol/min/mg
      protein) being significantly lower than that observed in female controls (0.44 +/
      0.02 nmol/min/mg protein; P < 0.01). ANOVA analysis examining the significance
      of differences in DPD activity among various groups indicated that only disease
      difference (breast cancer versus normal subjects) was significant after
      adjustments for race and age. In the present study, 21 (5.8%) patients were
      considered to be DPD deficient, indicating that this pharmacogenetic syndrome may
      be more common than anticipated (no DPD-deficient individual was found in the
      controls). Significantly lower DPD activity in patients with breast cancer may
      predispose to 5-FU-associated toxicity. These results provide further rationale
      for individualizing the 5-FU dose, thus reducing the risk of toxicity and/or
      improving therapeutic efficacy in patients with breast cancer.

PMID- 9516919
TI  - Influence of amifostine on the pharmacokinetics of cisplatin in cancer patients.
AB  - The pharmacokinetics of cisplatin was investigated in 13 patients receiving 18
      courses of cisplatin alone or in combination with amifostine to investigate the
      influence of amifostine (WR 2721; Ethyol) on the pharmacokinetics of cisplatin.
      Cisplatin was administered as a 1-h i.v. infusion, whereas amifostine was given
      i.v. over 15 min just before the cisplatin infusion. An increase in the final
      half-life of ultrafilterable platinum was observed after treatment with cisplatin
      and amifostine (t1/2, 0.77 +/- 0.10 h; n = 8), compared to cisplatin alone (t1/2,
      0.57 +/- 0.15 h; n = 8). This might be caused by an influence of amifostine on
      the kidney function, because an increase in the serum creatinine levels was also
      observed 24 h after treatment with cisplatin and amifostine (13.8 +/- 12.6%; n =
      9), which was not observed after treatment with cisplatin alone (-0.1 +/- 6.8%; n
      = 9). Surprisingly, the final half-life of unchanged cisplatin did not increase,
      but even showed a slight decrease after treatment with amifostine. In vitro data
      would suggest that this might be due to a chemical interaction between cisplatin
      and amifostine. Because the AUC values of ultrafilterable platinum and unchanged
      cisplatin did not change significantly and no change in Pt-DNA adduct (Pt-GG)
      levels in leukocytes was observed upon addition of amifostine in the treatment
      schedule, the change in the pharmacokinetics of cisplatin is most probably of
      minor importance and has no significant impact on the efficacy of cisplatin, as
      already confirmed by clinical studies.

PMID- 9516920
TI  - Quantitation of DNA from exfoliated colonocytes isolated from human stool surface
      as a novel noninvasive screening test for colorectal cancer.
AB  - The only widely used screening test for early detection of colorectal cancer, the
      fecal occult blood test, lacks both sensitivity and specificity because it relies
      upon incidental bleeding rather than the neoplastic process. With the purpose of
      developing a new noninvasive diagnostic approach, we quantified DNA extracted
      from cells isolated from the surface of human stools by a novel procedure. Stools
      collected from 28 healthy individuals, 17 colorectal cancer patients, and 11
      colorectal polyp patients were analyzed. A stool DNA index (SDNAI), expressed as
      DNA amount in nanograms per gram of stool, had a remarkable 4.5-fold difference
      in mean values between colorectal cancer patients and healthy people of
      comparable age. SDNAI was 2133 +/- 407 in the cancer group versus 469 +/- 65 in
      healthy people of the older (> 50 years) age group (P = 0.0005). The difference
      was independent of tumor location and size. If 700 ng of DNA/g of stool was taken
      as a cutoff SDNAI value in discrimination between older healthy people and cancer
      patients, sensitivity and specificity values reached 1.00 and 0.81, respectively.
      Age dependence of SDNAI was demonstrated by substantially lower SDNAI values
      (mean, 227 +/- 41) in younger healthy individuals. Polyp patients sometimes
      displayed elevated SDNAI values, but considerable variation was observed (mean,
      1215 +/- 548). These preliminary findings indicate that SDNAI provides a novel,
      simple, and powerful noninvasive test for colorectal cancer early detection and
      screening. The fundamental advantage of the SDNAI is that it directly
      characterizes colonic epithelium involved in carcinogenesis.

PMID- 9516921
TI  - Dissemination of tumor cells in patients undergoing surgery for colorectal
      cancer.
AB  - The majority of patients with colorectal cancer present at a stage when the
      primary cancer can be resected with curative intent. However, despite the high
      resectability rate, about 30-50% of these patients subsequently develop
      metastatic disease. In these patients, neoplastic cells were disseminated either
      before or during surgery of the primary cancer. Due to the lack of appropriate
      detection systems, the extent of pre- and intraoperative hematogenic tumor cell
      dissemination has not yet been determined. Using a reverse transcription-PCR
      assay to amplify cytokeratin 20 transcripts, we were able to detect 10 colorectal
      cancer cells in 10 ml of blood. Blood samples were taken from 65 patients
      undergoing resection of primary colorectal cancer or liver metastasis of
      colorectal cancer pre-, intra-, and postoperatively. Circulating tumor cells were
      detected in 24 of 58 patients with colorectal resections in correlation to the
      tumor stage and in 6 of 7 patients who underwent hemihepatectomy for liver
      metastasis. In 8 of 58 patients with colorectal resection and in 5 of 7 patients
      with hemihepatectomy, tumor cells could only be detected during or during and
      after surgery. These results demonstrate that hematogenic tumor cell
      dissemination is a frequent and early event in colorectal cancer. Surgery
      enhances the release of tumor cells into the circulation. The long-term follow-up
      of our patient cohort will provide data on the prognostic relevance of
      circulating tumor cells and might lead to new therapeutic concepts for
      perioperative prophylaxis of tumor cell implantation or postoperative adjuvant
      therapy regimens.

PMID- 9516922
TI  - Sequence-dependent hematological toxicity associated with the 3-hour
      paclitaxel/cyclophosphamide doublet.
AB  - Paclitaxel is active in metastatic breast cancer. Combination studies have
      demonstrated complex interactions between paclitaxel and other cytotoxic agents,
      including sequence-dependent cytotoxic, toxicological, and pharmacological
      effects. The principal objectives of this study were to determine the maximum
      tolerated doses of paclitaxel (3-h infusion) and cyclophosphamide (1-h infusion)
      administered every 3 weeks with granulocyte colony-stimulating factor
      (Filgrastim) and to determine if the sequence-dependent toxicological effects
      that have previously been observed with this combination when paclitaxel was
      administered over 24 h were evident when paclitaxel was administered over 3 h.
      Fifteen women with metastatic breast cancer were treated. Starting doses were 200
      mg/m2 paclitaxel and 1600 mg/m2 cyclophosphamide, with granulocyte colony
      stimulating factor (5 micrograms/kg/day) given s.c. beginning 24 h after
      chemotherapy. Doses of both drugs were escalated in cohorts of at least four
      patients. The sequence of drug administration was alternated with each
      consecutive patient and with each subsequent course of therapy in each individual
      patient, enabling the evaluation of sequence-dependent toxicological and
      pharmacological effects. Severe myelosuppression was the principal dose-limiting
      toxicity for this regimen, precluding dose escalation above 200 mg/m2 paclitaxel
      and 1600 mg/m2 cyclophosphamide, the maximum tolerated dose for this combination
      on this schedule. As has been previously demonstrated with this combination, when
      paclitaxel is administered over 24 h, the hematopoietic toxicity was sequence
      dependent. Paired analysis of toxicity data using each patient as her own control
      indicated more severe hematological toxicity in courses in which paclitaxel was
      administered first. There was no evidence of sequence-dependent effects on the
      pharmacokinetics of these drugs that might account for this phenomenon. The
      impact of drug sequencing on toxicity should be considered in the further
      development of combination therapy containing alkylating agents and paclitaxel,
      when the latter is administered over 3 h.

PMID- 9516924
TI  - Frequent detection of ras and p53 mutations in brush cytology samples from lung
      cancer patients by a restriction fragment length polymorphism-based "enriched
      PCR" technique.
AB  - RFLP-mediated PCR has been successfully applied as a reliable tool in the
      detection of ras mutations in many cancers and provides a basis for "mutant
      enriched PCR" protocols. We have, therefore, modified this technique to the
      sensitive detection of K-ras codon 12 and also p53 "hot spot" mutations, which,
      frequently in lung cancer, affect codons at the positions 157, 175, 245, 248,
      249, and 273. With a high sensitivity of 1 mutant allele in 10(4) normal alleles,
      our enrichment assay allows the detection of oncogene alleles when only a few
      tumor cells are present within a normal cell population. Brush cytology material
      obtained from the tumor site of 20 patients with endoscopically apparent
      bronchial carcinoma was compared to macroscopically normal mucosa taken from the
      contralateral bronchus ("control" cytology). We found K-ras codon 12 mutations in
      5 cases (25%) and p53 mutations in 13 cases (65%) in the tumor-derived cell
      material but, with the exception of two cases, not in cell material taken from
      the control cytology. Seventy-five % of the samples analyzed showed that at least
      one of the two oncogenes was affected. In several cases, two p53 lesions were
      detected concomitantly. The majority of the mutations could be reconfirmed by an
      alternative approach exploiting changes in the genomic RFLP pattern induced by
      these mutations and were also demonstrated in separate diagnostic biopsies taken.
      Thus, we conclude that the established enriched PCR protocol ensures a high
      sensitivity and preserved specificity for the diagnosis of oncogene lesions
      associated with lung cancer. Because conventional techniques normally yield a
      lower incidence of corresponding ras and p53 mutations, we think that both the
      high rate and the heterogeneity of p53 mutations found in some cases are, indeed,
      related to the increased sensitivity of this new enriched PCR technique.

PMID- 9516923
TI  - Phase II trial of topotecan administered as 72-hour continuous infusion in
      children with refractory solid tumors: a collaborative Pediatric Branch, National
      Cancer Institute, and Children's Cancer Group Study.
AB  - The antitumor activity of topotecan administered as a 72-h continuous i.v.
      infusion was evaluated in children with refractory neuroblastoma and sarcomas of
      soft tissue and bone. We also attempted to increase the dose intensity of
      topotecan by including an intrapatient dose escalation in the trial design.
      Ninety-three children (85 eligible and evaluable for response) with recurrent or
      refractory neuroblastoma, osteosarcoma, Ewing's sarcoma/peripheral
      neuroectodermal tumor, rhabdomyosarcoma, or other soft-tissue sarcomas received
      topotecan administered as a 72-h i.v. infusion every 21 days. The initial dose
      was 1.0 mg/m2/day, with subsequent intrapatient dose escalation to 1.3 mg/m2/day
      for those patients who did not experience dose-limiting toxicity after their
      first cycle of topotecan. There was one complete response in a patient with
      neuroblastoma (n = 26) and one partial response in a patient with Ewing's
      sarcoma/peripheral neuroectodermal tumor (n = 25). No complete or partial
      responses were observed in 17 patients with osteosarcoma, 15 patients with
      rhabdomyosarcoma, or 2 patients with other soft-tissue sarcomas; however, 8
      patients had prolonged (15-48 weeks) stable disease while receiving topotecan.
      Topotecan was well tolerated. The most commonly observed toxicities were
      myelosuppression (dose-limiting) and nausea and vomiting. Intrapatient dose
      escalations were performed in 68% of the patients who received more than one
      cycle of topotecan, and 1.3 mg/m2/day was tolerated by 79% of the patients who
      received the higher dose and were evaluable for hematological toxicity. In
      conclusion, topotecan administered as a 72-h continuous infusion every 21 days is
      inactive (objective response rate, < 20%) in children with refractory or
      recurrent neuroblastoma and sarcomas of soft tissue or bone.

PMID- 9516925
TI  - The relationship between concentrations of circulating soluble E-selectin and
      clinical, pathological, and biological features in patients with breast cancer.
AB  - Increasing evidence suggests that E-selectin contributes to tumor growth and
      metastasis. E-selectin may increase tumoral angiogenesis and the adhesion of
      tumoral cells to endothelial cells at distant sites. The aim of this study was to
      assess the relationship between concentrations of circulating soluble E-selectin
      (sE-selectin) and clinical, pathological, and biological features in patients
      with breast cancer (BC). Concentrations of sE-selectin were analyzed by an ELISA
      method in sera from 113 patients with metastatic BC, 30 patients with primary
      inflammatory BC, 105 patients with primary noninflammatory BC, and 42 healthy
      controls. These concentrations were analyzed in terms of the clinical and
      pathological features of the tumors as well as in terms of the concentrations of
      serum inflammatory parameters (erythrocyte sedimentation rate, C reactive
      protein, interleukin 1 beta, and tumor necrosis factor alpha), the response to
      chemotherapy or hormone therapy, and the survival duration. Tumoral angiogenesis
      was also assessed in 68 patients with primary noninflammatory BC who had had
      primary surgery. The mean concentration of sE-selectin in the metastatic BC group
      was significantly higher than the mean concentration found in the healthy control
      group (33.5 versus 21.8 ng/ml; P < 0.01). In metastatic BC, the mean
      concentration of sE-selectin was significantly higher in patients with liver
      metastasis than in patients without liver metastasis (55.3 versus 26.0 ng/ml; P <
      10(-5). The univariate analysis showed that high concentrations of sE-selectin
      were associated with reduced overall survival (P < 0.05), but this probably
      reflected the association between high concentrations of sE-selectin and liver
      metastasis. In patients with primary noninflammatory BC, a negative correlation
      was found between sE-selectin concentrations and the tumoral microvessel count (r
      = -0.47; P = 10(-4). In patients with primary inflammatory or noninflammatory BC,
      no correlation was found between concentrations of sE-selectin and tumor size,
      lymph node involvement, response to chemotherapy or hormone therapy, and
      survival. No correlation was found between the concentrations of sE-selectin and
      serum inflammatory parameters in any of the patient groups. This study suggests
      that in patients with metastatic BC, levels of sE-selectin are higher in the
      presence of liver metastasis. In patients with primary BC, high concentrations
      seem to be associated with reduced tumoral angiogenesis. Although several studies
      have previously demonstrated that the expression of cell surface E-selectin
      enhances the metastatic process, the shedding of sE-selectin in circulation may
      be considered a mechanism of inhibition of tumor progression.

PMID- 9516926
TI  - Reduced expression of interleukin 6 in undifferentiated thyroid carcinoma: in
      vitro and in vivo studies.
AB  - Cytokines appear to play an important role in the development and progression of
      epithelial tumors. Cultured normal human thyroid follicular cells constitutively
      release high levels of interleukin-6 (IL-6) and IL-8, together with low to
      moderate levels of transforming growth factor-alpha (TGF-alpha) and TGF-beta. IL
      6 appears to play multiple functions in thyroid physiology and disease. Because
      certain data indicate an inverse relationship between IL-6 production and
      epithelial tumor aggressiveness, we used both tissue culture methods and
      histochemical techniques to search for possible alterations of cytokine
      expression in thyroid carcinomas. As compared to cultures from normal tissue and
      well-differentiated carcinoma, production of IL-6 was strongly down-regulated in
      cultures derived from undifferentiated carcinoma. In contrast, levels of IL-8,
      TGF-alpha, and TGF-beta produced by neoplastic TFC were similar to those produced
      by normal cells. Actually, production of TGF-alpha was slightly enhanced in
      cultures from well-differentiated carcinoma. Immunoassay results were confirmed
      by reverse transcriptase-PCR analysis. Immunohistochemistry of human thyroid
      carcinomas (n = 99) and normal thyroid tissue (n = 85) showed that immunoreactive
      IL-6 was strongly diminished in undifferentiated forms (n = 34) and slightly
      reduced in well-differentiated carcinoma (n = 65). In agreement with the in vitro
      results, TGF-alpha expression was significantly increased in neoplastic
      thyrocytes, as compared to their normal counterpart. The results indicate that,
      as in the mammary and salivary glands, down-regulation of IL-6 expression may
      represent a marker of undifferentiated thyroid carcinoma.

PMID- 9516927
TI  - Levels of multidrug resistance (MDR1) P-glycoprotein expression by human breast
      cancer correlate with in vitro resistance to taxol and doxorubicin.
AB  - To determine whether multidrug resistance (MDR1) P-glycoprotein (Pgp) expression
      correlated with clinical MDR1-related drug resistance, we established a protocol
      for quantitative measurement of Pgp expression and in vitro drug resistance in
      doxorubicin resistant MCF7 breast cancer cell lines and 359 freshly resected
      specimens of breast carcinoma. Pgp expression was detected with 4E3, UIC2, and
      JSB-1 monoclonal antibodies using flow cytometry and immunohistochemistry (IHC).
      Pgp function was determined using PSC833 in a drug resistance-reversal assay and
      with a three-dimensional agarose-based extreme drug resistance assay. MCF7
      calibrator cell lines expressed Pgp, which was functional and in proportion to
      the degree of drug resistance. Flow cytometry, UIC2 shift assays, IHC scores, and
      determination of absorbance products by image analysis were all highly correlated
      (r > 0.9). Overall Pgp expression increased from 11% in untreated patients to 30%
      in patients who had previously received chemotherapy. Compared with Pgp-negative
      tumors, a significant increase in doxorubicin and Taxol resistance was seen for
      breast cancers that expressed Pgp, regardless of prior treatment. A strong
      correlation between the degree of Pgp expression and in vitro resistance to Taxol
      and doxorubicin (but not to 5-fluorouracil) was found when either IHC scores or
      image analysis-based methods were used to quantify Pgp expression (n = 185, P <
      0.0001). The degree of Pgp expression strongly correlated with the degree of drug
      resistance in the clinical specimens studied. These data suggest that (a) Pgp
      contributes to clinical MDR1-related drug resistance, and (b) both intrinsic and
      acquired expression of Pgp in breast cancer may contribute in part to therapeutic
      failure and relapse.

PMID- 9516928
TI  - Quantitative differences in telomerase activity among malignant, premalignant,
      and benign ovarian lesions.
AB  - Telomerase activation has been demonstrated in both cancers and some noncancerous
      lesions. However, few studies have determined levels of telomerase activity in
      these lesions. In the present study, using a recently developed stretch PCR
      assay, telomerase activity was quantitatively determined in a variety of ovarian
      lesions including 36 ovarian cancers, 5 ovarian low potential malignancy (LPM)
      lesions, 10 ovarian cysts, and 12 normal ovaries. Telomerase activity was
      normalized to control activity (100 units) in C33A cell line and given in
      relative units. Telomerase activity in ovarian cancer (51 +/- 7 units, mean +/-
      SE) was significantly higher than that in LPM lesions, ovarian cysts, and normal
      ovaries (7 +/- 3, 10 +/- 2, and 10 +/- 2 units, respectively; P < 0.001).
      Interestingly, all LPMs, ovarian cysts, and normal ovaries exhibited low
      telomerase activity less than 30 units, and no significant difference in level of
      telomerase activity was found among them. We also found a significant correlation
      between the level of telomerase activity and the clinical stage of ovarian
      cancer. Our quantitative telomerase assay thus clearly distinguished telomerase
      activity in ovarian cancers from that in LPM lesions and ovarian cysts.
      Significant levels of telomerase activation frequently occurred in cancer but
      rarely occurred in premalignant and benign lesions, suggesting that telomerase
      activation is a critical step in cancer development.

PMID- 9516929
TI  - Prognostic value of alpha 6 beta 4 integrin expression in breast carcinomas is
      affected by laminin production from tumor cells.
AB  - Immunocytochemical analysis of breast carcinoma specimens for alpha 6 beta 4
      integrin expression and other different pathobiological markers revealed beta 4
      integrin subunit expression in 36 of 80 cases analyzed and a significant
      association only with alpha 6 integrin subunit expression (P < 0.01) and laminin
      production (P = 0.01) by tumor cells. Survival analysis indicated that beta 4 and
      alpha 6 expression are associated with poor prognosis (P = 0.02), whereas laminin
      production showed only borderline association (P = 0.06). However, analysis of
      disease outcome in relation to expression of both alpha 6 beta 4 and laminin
      indicated best outcomes for patients with tumors producing laminin but not
      expressing alpha 6 beta 4 integrin, whereas worst outcomes were observed for
      alpha 6 beta 4- and laminin-positive tumors, indicating that alpha 6 beta 4
      expression was associated with prognosis, mainly in the laminin-producing tumor
      subset. These data indicate that the prognostic value of alpha 6 beta 4 integrin
      expression is affected by laminin production from tumor cells and suggest that
      interaction between these two molecules mediates distinct signals that are
      important for tumor progression.

PMID- 9516930
TI  - Assessment of messenger RNA of beta 1-->4-N-acetylgalactosaminyl-transferase as a
      molecular marker for metastatic melanoma.
AB  - Gangliosides GM2 [GalNAc beta 1-4(NeuAc alpha 2-3)Gal beta 1-4Glc beta 1-1Cer]
      and GD2 [GalNAc beta 1-4(NeuAc alpha 2-8NeuAc alpha 2-3)Gal beta 1-4Glc beta 1
      1Cer] are cell surface tumor-associated antigens and have been demonstrated to be
      important markers of human malignant melanoma progression. Expression of these
      glycolipid antigens on melanoma tissues can be assessed by immunohistochemistry
      or biochemical analysis. These methodologies, however, are not logistically
      practical or sensitive for testing metastatic melanoma cells in blood or in
      tissue biopsies. In the present study, we hypothesized that the enzyme involved
      in GM2 and GD2 synthesis, beta 1-->4-N-acetylgalactosaminyltransferase (beta 1-
      >4GalNac-T), can be a useful marker for detection of occult metastatic melanoma.
      A reverse transcription PCR and Southern blot assay to detect beta 1-->4GalNac-T
      mRNA expression was developed. Beta 1-->4GalNac-T mRNA was detected in all 13
      melanoma cell lines tested. Metastatic melanoma of lymph nodes and different
      organ sites expressed beta 1-->4GalNac-T mRNA at various levels. Detection
      sensitivity of the reverse transcription PCR assay was 1 ng of total RNA
      extracted from tumor specimens and approximately 5 melanoma cells in 20 million
      normal donor peripheral blood lymphocytes. In assessment of blood from 126
      melanoma patients, beta 1-->4GalNac-T mRNA was more frequently found in advanced
      stage melanomas and in patients showing more aggressive tumor progression. Normal
      donor blood samples (n = 37) were all negative for beta 1-->4GalNac-T mRNA
      expression. These results suggest that beta 1-->4GalNac-T mRNA is a promising
      molecular marker for detecting melanoma cells, characterizing antigen expression,
      and monitoring tumor progression.

PMID- 9516931
TI  - Prognostic significance of peripheral blood and bone marrow tyrosinase messenger
      RNA in malignant melanoma.
AB  - The objectives of this study were to evaluate the prognostic significance of
      reverse transcription PCR (RT-PCR) detection of tyrosinase mRNA in the peripheral
      blood (PB) and bone marrow (BM) of patients with stage II-IV malignant melanoma
      (MM). Seventy-three PB samples and 109 BM aspirates from 123 assessable patients
      with stage II-IV MM were analyzed for tyrosinase mRNA using nested RT-PCR. Twenty
      five controls without MM were also evaluated. The RT-PCR results were correlated
      with overall survival (OS) and clinical stage. Overall, 23 of the 123 patients
      with MM (19%) had tyrosinase mRNA in their blood and/or BM. RT-PCR positivity was
      present in the PB of 9 of 73 patients (12%), whereas 18 of 109 (16.5%) had
      tyrosinase mRNA in their BM. All controls were tyrosinase PCR negative. There was
      no correlation between RT-PCR results and clinical stage. Within stage II, BM PCR
      positive patients had a shorter median survival (24 months) than BM PCR-negative
      individuals (median not reached), with a P approaching significance (P = 0.06).
      There was a statistically significant correlation between blood PCR positivity
      and decreased overall survival (P = 0.03) in all patients. Blood PCR positivity
      was associated with a significantly decreased OS in stage II and III (P = 0.01
      and 0.02, respectively) and was not a predictor of OS in stage IV. In
      multivariate analysis, blood RT-PCR for tyrosinase mRNA was found to be an
      independent predictor of survival (P = 0.03; risk ratio, 2.87). RT-PCR can
      specifically detect tyrosinase mRNA in the PB and BM of patients with MM. Blood
      RT-PCR is an independent predictor of overall survival in stage II-III MM.
      Additional studies are needed to define the potential role of this assay in the
      management of patients with advanced melanoma.

PMID- 9516933
TI  - Careful histological confirmation and microdissection reveal telomerase activity
      in otherwise telomerase-negative breast cancers.
AB  - Studies of invasive breast cancers consistently identify a subset of tumors
      without telomerase activity, compromising its utility as a tumor marker.
      Telomerase-negative tumors may represent a biologically different subset, or the
      result could be attributed to assay imperfections. To resolve this issue, we
      tested 105 invasive breast cancers for telomerase activity and found that 23
      (22%) tumors were telomerase negative. Careful histological confirmation of an
      adjacent cryosection and/or microdissection of pure tumor cells reduced this
      number to 5 (5%). Thus, truly telomerase-negative invasive breast cancers are
      rare, making this enzyme a potentially very useful tumor marker in breast cancer.

PMID- 9516932
TI  - Significance of platelet-derived endothelial cell growth factor in the
      angiogenesis of human gastric cancer.
AB  - We have previously shown that platelet-derived endothelial cell growth factor (PD
      ECGF) is associated with angiogenesis of human colon cancer; this factor is
      expressed at high levels in vascular tumors that express low levels of vascular
      endothelial growth factor (VEGF). In these colon cancers, the major source of PD
      ECGF is the infiltrating cells. In this study, we examined the role of PD-ECGF in
      the angiogenesis of human gastric cancer. Immunostaining for PD-ECGF was done on
      93 gastric cancers previously stained for VEGF, basic fibroblast growth factor,
      and factor VIII-related antigen (specific for endothelial cells). To determine
      the cell type expressing PD-ECGF, double staining was done using antibodies to
      both PD-ECGF and CD68 (specific for macrophages). PD-ECGF was expressed more
      frequently in infiltrating cells (positive CD68 staining; 53.8%) than in tumor
      epithelium (9.7%; P < 0.0001). Infiltrating cells simultaneously stained positive
      for both PD-ECGF and CD68. An association between PD-ECGF expression in
      infiltrating cells, VEGF expression in tumor epithelium, and vessel count was
      observed in intestinal-type gastric cancer but not in diffuse-type gastric
      cancer. Vessel count was greater in tumors with high expression of both PD-ECGF
      and VEGF than in those with high expression of either factor alone (P = 0.002).
      Multiple angiogenic factors expressed by both tumor cells and infiltrating cells
      may play a role in the regulation of angiogenesis in intestinal-type gastric
      cancer.

PMID- 9516934
TI  - A comparison between microsatellite and quantitative PCR analyses to detect
      frequent p16 copy number changes in primary bladder tumors.
AB  - We tested 70 primary bladder tumors for altered copy number of p16 (D9S1752) by
      microsatellite analysis and by a quantitative PCR (QPCR) assay. These two
      approaches were fully concordant for 53 tumors, including all 39 tumors in which
      microsatellite analysis detected loss. In addition, the QPCR method detected
      useful anomalies in 17 additional cases, including those in which D9S1752 was
      uninformative. QPCR was abnormal in 56 of 70 (80%) cases, whereas microsatellite
      analysis was abnormal in 39 of 70 (56%) cases. Although QPCR uses more DNA than
      microsatellite analysis, it represents a rapid, informative technique that can
      readily detect both chromosome 9p21 deletions and amplifications in primary
      bladder tumors without the need for electrophoretic separation.

PMID- 9516935
TI  - Sequential treatment of human chronic lymphocytic leukemia with bryostatin 1
      followed by 2-chlorodeoxyadenosine: preclinical studies.
AB  - We have previously reported that bryostation 1 (Bryo 1) induces differentiation
      of chronic lymphocytic leukemia (CLL) in vitro to a hairy cell (HC) stage. This
      study tests the hypothesis that Bryo 1-differentiated CLL cells are more
      susceptible to 2-chlorodeoxyadenosine (2-CdA) than parent CLL cells. A recently
      established EBV-negative CLL line (WSU-CLL) from a patient resistant to
      chemotherapy including fludarabine was used to test this hypothesis. Both Bryo 1
      (10-1000 nM) and 2-CdA (5.6-22.4 microM) exhibited a dose-dependent growth
      inhibitory effect on the WSU-CLL cell line. In vitro, the sequential exposure to
      Bryo 1 (100 nM for 72 h) followed by 2-CdA (11.2 microM) resulted in
      significantly higher rates of growth inhibition than either agent alone. Changes
      in immunophenotype, enzymes, lipids, proteins, and the DNA of WSU-CLL cells were
      studied before and after Bryo 1 treatment. Bryo 1 induced a positive tartrate
      resistant acid phosphatase reaction and two important markers, CD11c and CD25,
      after 72 h of culture, confirming the differentiation of CLL to HC. The Fourier
      transformation infrared spectroscopic analysis showed that the amount of membrane
      lipids significantly increased in Bryo 1-treated cells compared to controls after
      24 h, whereas the protein content, as well as the DNA content, decreased. This
      finding supports the change of CLL to HC. To evaluate the in vivo efficacy of
      Bryo 1 and 2-CdA, we used a xenograft model of CLL in WSU-CLL-bearing mice with
      severe combined immune deficiency. s.c. tumors were developed by injection of
      10(7) WSU-CLL cells, and fragments were then transplanted into a new batch of
      severe combined immunodeficient mice. Bryo 1 and 2-CdA at the maximum tolerated
      doses (75 micrograms/kg i.p. and 30 mg/kg s.c., respectively) were administered
      to the mice at different combinations and schedules. The survival in days, the
      tumor growth inhibition ratio, the tumor growth delay, and the log10 kill of the
      mice treated with Bryo 1 followed by 2-CdA were significantly better than the
      control and other groups. We conclude that the sequential treatment with Bryo 1
      followed by 2-CdA resulted in higher antitumor activity and improved animal
      survival.

PMID- 9516936
TI  - Altered irinotecan and SN-38 disposition after intravenous and oral
      administration of irinotecan in mice bearing human neuroblastoma xenografts.
AB  - The antitumor activity of irinotecan in vitro primarily results from its
      hydrolysis by carboxylesterase to the active metabolite SN-38. The present study
      was conducted to evaluate the effect of human neuroblastoma xenografts on
      irinotecan and SN-38 disposition after i.v. and oral irinotecan administration.
      Non-tumor-bearing mice and mice bearing three different human neuroblastoma
      xenograft lines (NB1691, NB1643, and NBEB) were given irinotecan (10 mg/kg) by
      short i.v. injection into the tail vein or by oral gavage. Serial plasma samples
      were obtained, processed to isolate irinotecan and SN-38 lactone, and assayed
      with a sensitive and specific high-performance liquid chromatography assay.
      Noncompartmental and compartmental pharmacokinetic analyses were performed. A
      four-compartment model was used for analysis of irinotecan and SN-38
      concentration-time data after i.v. administration. The presence of tumor
      increased irinotecan systemic exposure (1.2-3.8-fold; P < 0.05) after i.v. and
      oral administration in mice bearing neuroblastoma xenografts compared to non
      tumor-bearing mice. Moreover, SN-38 systemic exposures were higher (1.3-3.8-fold;
      P < 0.05) in mice bearing human neuroblastoma xenografts as compared to non-tumor
      bearing mice, with the greatest effect observed after oral administration of
      irinotecan. A schematic model is presented to provide a mechanistic basis for our
      observations. These results emphasize the need to perform preclinical
      pharmacokinetic studies to evaluate the influence of tumor on drug disposition.

PMID- 9516937
TI  - Activity of fotemustine in medulloblastoma and malignant glioma xenografts in
      relation to O6-alkylguanine-DNA alkyltransferase and alkylpurine-DNA N
      glycosylase activity.
AB  - Fotemustine is a chloroethylnitrosourea with antitumor activity in disseminated
      melanoma and adult primary brain tumors. Because new drugs are required for the
      treatment of medulloblastoma in children, we evaluated the preclinical antitumor
      activity of fotemustine in four s.c. medulloblastoma xenografts, in comparison
      with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). Both drugs were administered as
      a single i.p. injection to nude mice bearing advanced-stage tumor. Fotemustine
      displayed significant antitumor activity in three of four medulloblastoma
      xenografts; two, IGRM34 and IGRM57, were highly sensitive, with 37 and 100% tumor
      free survivors, respectively, more than 120 days after treatment at the highest
      nontoxic dose (50 mg/kg). Fotemustine was also highly active in a malignant
      glioma xenograft (IGRG88; five of six tumor-free survivors on day 177).
      Fotemustine proved to be significantly more active than BCNU in IGRM34 and the
      glioma xenograft IGRG88. The DNA repair protein O6-alkylguanine-DNA
      alkyltransferase (ATase) was detected in all tumor xenografts, ranging in
      activity from 6 to 892 fmol/mg protein. The high in vivo sensitivity to
      fotemustine and BCNU observed in three xenografts was clearly associated with a
      low ATase activity (> 20 fmol/mg), whereas the two poorly sensitive or refractory
      medulloblastoma xenografts showed high ATase activity (> 500 fmol/mg).
      Alkylpurine-DNA N-glycosylase activity was detected in all tumor xenografts but
      at levels ranging only from 513 to 1105 fmol/mg/h; no consistent relationship was
      found between alkylpurine-DNA N-glycosylase activity and the in vivo sensitivity
      to the two chloroethylnitrosoureas. The improved activity and tolerance of
      fotemustine in comparison with BCNU in pediatric medulloblastoma xenografts
      strongly support the clinical development of this agent in children with brain
      tumors, in which ATase should be examined as a potential prognostic indicator.

PMID- 9516939
TI  - Heterogeneity of O6-alkylguanine-DNA-alkyltransferase measured by flow cytometric
      analysis in blood and bone marrow mononuclear cells.
AB  - Alkyltransferase (AGT) repairs alkylation at O6-guanine in DNA and is a major
      determinant of susceptibility to alkylating chemotherapeutic agents and
      carcinogens. Using a newly developed flow cytometry assay with the monoclonal
      anti-AGT antibody, mT3.1, we compared AGT expression in single-cell suspensions
      with standard biochemical and Western blot assays to validate the fluorescence
      activated cell sorting (FACS) method and develop potential applications. From
      Chinese hamster ovary cells (CHO) transfected with human O6-methylguanine-DNA
      methyl-transferase cDNA, 6 CHO-O6-methylguanine-DNA methyl-transferase clones
      were isolated that expressed 0.3 to 64 fmol/microgram DNA (by biochemical assay)
      of human AGT. FACS yielded a linear relationship between mean fluorescence
      intensity and both AGT activity by biochemical assay and AGT protein by Western
      blot. Using this standard curve, FACS-analyzed AGT protein content in human
      peripheral blood mononuclear cells (PBMCs) from normal donors ranged from 6.1 to
      12.8 fmol/microgram DNA, similar to those obtained by biochemical assay and
      Western blot. This suggests that the level of immunoreactive protein appears to
      be an accurate predictor of AGT activity in the steady state. FACS-AGT in PBMCs
      from normal donors had a low index of heterogeneity within the sample. In
      contrast, by FACS-AGT analysis of human bone marrow samples and granulocyte
      colony-stimulating factor-mobilized PBMCs, AGT was lower and had an 8-fold higher
      index of heterogeneity than observed in PBMCs from normal donors. After treatment
      with O6-benzylguanine (O6-bG), Western and FACS-AGT detected significant levels
      of AGT protein for up to 24 h, whereas biochemical assay showed AGT activity less
      than 5% of the basal level. Because only the biochemical assay accurately
      measures net AGT activity, the AGT-FACS assay will not be useful in clinical
      trials to assess the efficacy of O6-bG or other AGT inhibitors. Thus, AGT-FACS
      can rapidly assess the heterogeneity of steady-state AGT in single-cell
      suspensions and may be useful for assay in lymphocytes, bone marrow cells,
      leukemic myeloma plasma cells, or cells transfected with the AGT gene; Western
      blot analysis is better for small samples such as tumor biopsies, whereas
      biochemical assay is best able to measure enzyme activity and its inactivation by
      O6-bG or other agents.

PMID- 9516938
TI  - Pretreatment of colon carcinoma cells with Tomudex enhances 5-fluorouracil
      cytotoxicity.
AB  - The cytotoxic effect of sequence and dose of Tomudex (TX) and 5-fluorouracil
      (FUra) on an HCT-8 colon carcinoma cell line using a clonogenic assay was
      evaluated. Synergistic cell kill was obtained with 24 h of exposure to TX
      followed by 4 h of exposure to FUra. Marginal synergy was obtained with the same
      sequence but with a 5-day exposure to FUra. The reverse sequence, FUra (either 4
      h or 5 days), followed by TX (24 h), resulted in less-than-additive cell kill.
      The synergistic effect was not due to augmented inhibition of thymidylate
      synthase, as determined by the measurement of thymidylate synthase activity by
      tritium release from [5-3H]2'-deoxyuridine. Surprisingly, an increase in
      intracellular levels of phosphoribosylpyrophosphate was observed after 24 h of
      exposure to TX, suggesting the possibility of an indirect effect of TX and/or its
      polyglutamates on purine biosynthesis. Moreover, we observed an increased
      formation of FUra nucleotides in the cells preexposed to TX, likely due to the
      increased intracellular levels of phosphoribosylpyrophosphate, that as a
      consequence led to an enhanced incorporation of FUra into RNA and increased cell
      killing.

PMID- 9516940
TI  - Acute in vivo resistance in high-dose therapy.
AB  - In the design of sequential high-dose chemotherapy regimens, the selection of
      antitumor alkylating agents to be included in each intensification and the
      interval between the intensifications are critical to the design of the therapy.
      The tumor cell survival assay and tumor growth delay assay using the murine EMT-6
      mammary carcinoma were used as a solid tumor model in which to address these
      issues. Tumor-bearing mice were treated with high-dose melphalan or
      cyclophosphamide followed 7 or 12 days later by melphalan, cyclophosphamide,
      thiotepa, or carboplatin. After treatment with melphalan both 7 and 12 days
      later, the tumor was resistant to each of the four drugs studied. After treatment
      with cyclophosphamide both 7 and 12 days later, the tumor was resistant to
      melphalan and thiotepa but was not resistant to cyclophosphamide or carboplatin.
      To extend the interval between high-dose treatments to 14 and 21 days, after the
      first intensification the tumor was transferred to second hosts that were either
      drug-treated or not drug treated. When high-dose melphalan-treated tumors were
      treated with a second high dose of melphalan, the tumors were very resistant with
      the 14-day interval and less resistant with the 21-day interval. This small
      effect was evident in the bone marrow colony-forming unit, granulocyte-macrophage
      (CFU-GM), except in the hosts pretreated with melphalan. When high-dose
      cyclophosphamide-treated tumors were treated with a second high dose of
      cyclophosphamide, drug resistance was observed both with the 14-day and 21-day
      interval if the host was non-pretreated or was pretreated with melphalan, but not
      if the host was pretreated with cyclophosphamide. The same was true in the bone
      marrow CFU-GM. Tumor growth delay studies supported these findings in that
      treatment with high-dose cyclophosphamide, melphalan, thiotepa, and carboplatin
      resulted in less than additive tumor growth delay, whereas treatment with high
      dose cyclophosphamide prior to treatment with high-dose melphalan,
      cyclophosphamide, thiotepa, or carboplatin resulted in additivity to greater-than
      additive tumor growth delay. High-dose combination regimens required dose
      reduction of the drugs, which resulted in decreased tumor growth delays.

PMID- 9516941
TI  - High susceptibility of human cancer xenografts with higher levels of cytidine
      deaminase to a 2'-deoxycytidine antimetabolite, 2'-deoxy-2'-methylidenecytidine.
AB  - 2'-Deoxy-2'-methylidenecytidine (DMDC) is a new 2'-deoxycytidine (dCyd)
      antimetabolite. The present study compared its antitumor activities with those of
      2',2'-difluorodeoxy-cytidine (gemcitabine) in 15 human cancer xenograft models.
      DMDC was highly resistant to cytidine (Cyd) deaminase, which deaminates the dCyd
      analogues to inactive molecules, whereas gemcitabine was susceptible to the
      enzyme. Given p.o., high antitumor activity with therapeutic index of more than
      10 was found with DMDC in 7 of 15 xenograft lines. In contrast, gemcitabine given
      i.v. or p.o. was highly effective in 4 of 15 human cancer xenograft lines. The
      antitumor spectrum of these compounds was quite different, although their
      molecular targets are reported to be similar. DMDC was highly effective in tumors
      with higher levels of Cyd deaminase activity, whereas it showed only slight
      activity in those with lower levels of Cyd deaminase. In contrast, gemcitabine
      appeared to be less effective in tumors with high levels of Cyd deaminase. We
      also investigated the correlation with the susceptibility to the two dCyd
      antimetabolites and dCyd kinase activity in tumors, but none was observed. Cyd
      deaminase activity was found to be high in tumor tissues from various types of
      human cancers thus far tested, such as colorectal cancer and non-small cell lung
      cancer. Such cancer types or individual patients who have tumors with high
      activity of the enzyme may be targets for DMDC therapy.

PMID- 9516942
TI  - Comparative study of the antitumor activity of free doxorubicin and polyethylene
      glycol-coated liposomal doxorubicin in a mouse lymphoma model.
AB  - Here, we investigate various factors affecting the therapeutic efficacy of free
      doxorubicin (Free-Dox) and polyethylene glycol (PEG)-coated (PEGylated) liposomal
      doxorubicin (referred to as Doxil) in the ascitic J6456 lymphoma model of BALB/c
      mice. Free drug and liposomal drug were affected differently by the tumor burden
      and route of treatment administration. A delay in start of treatment from day 1
      to day 5 almost completely abolished the efficacy of Free-Dox, whereas that of
      Doxil was only minimally reduced. Contrasting effects on the therapeutic efficacy
      of Free-Dox and Doxil were obtained by changing treatment administration from the
      i.v. to the i.p. route; the efficacy of free drug was relatively enhanced,
      whereas that of liposomal drug was relatively diminished. Overall, Doxil given by
      the systemic i.v. route was the most effective treatment in prolonging median
      survival and obtaining cures. Variations in the dose-schedule treatment regime
      confirm the superior therapeutic profile and reduced dependence on tumor burden
      of the PEGylated liposomal formulation over free drug. In addition, these
      experiments indicate that, at equal dose intensity, the dose level is more
      important than the frequency of administration for therapeutic activity.

PMID- 9516943
TI  - Phagocytosis of cross-linked gelatin matrix by human breast carcinoma cells
      correlates with their invasive capacity.
AB  - During invasion and metastasis, cancer cells interact closely with the
      extracellular matrix molecules by attachment, degradation, and migration. We
      demonstrated previously the local degradation of fluorescently labeled gelatin
      matrix by cancer cells at invasive membrane protrusions, called invadopodia.
      Using the newly developed quantitative fluorescence-activated cell sorting
      phagocytosis assay and image analysis of localized degradation of fluorescently
      labeled matrix, we document here that degradation and site-specific removal of
      cross-linked gelatin matrix is correlated with the extent of phagocytosis in
      human breast cancer cells. A higher phagocytic capacity is generally associated
      with increasing invasiveness, documented in other invasion and motility assays as
      well. Gelatin phagocytosis is time and cell density dependent, and it is mediated
      by the actin cytoskeleton. Most of the intracellular gelatin is routed to
      actively acidified vesicles, as demonstrated by the fluorescent colocalization of
      gelatin with acidic vesicles, indicating the intracellular degradation of the
      phagocytosed matrix in lysosomes. We show here that normal intracellular routing
      is blocked after treatment with acidification inhibitors. In addition, the need
      for partial proteolytic degradation of the matrix prior to phagocytosis is
      demonstrated by the inhibition of gelatin phagocytosis with different serine and
      metalloproteinase inhibitors and its stimulation by conditioned medium containing
      the matrix metalloproteinases MMP-2 and MMP-9. Our results demonstrate that
      phagocytosis of extracellular matrix is an inherent feature of breast tumor cells
      that correlates with and may even directly contribute to their invasive capacity.
      This assay is useful for screening and evaluating potential anti-invasive agents
      because it is fast, reproducible, and versatile.

PMID- 9516944
TI  - bcl-2, bax, bcl-XL, and bcl-XS expression in normal and neoplastic ovarian
      tissues.
AB  - The bcl-2 family of proteins includes some important regulators of apoptosis.
      Among these, bcl-2 and bcl-xL prevent cells from entering apoptosis, whereas bax
      and bcl-xS can induce cell death. Alterations in the control of this process can
      lead to a decrease in cell death, thus contributing to neoplastic growth.
      Diminished susceptibility to chemotherapy has also been attributed, in in vitro
      systems, to alterations in the levels of bcl-2, bax, or bcl-x. We analyzed the
      expression of bcl-2, bax, bcl-xL, and bcl-xS in normal and neoplastic ovarian
      tissues by reverse transcriptase-PCR and Western blotting. The RNA and protein
      levels were significantly correlated for all genes. Interestingly, the levels of
      these genes in normal and neoplastic tissues were significantly different: bcl-2
      was higher in normal tissue (P < 0.002), whereas bax and bcl-xL were higher in
      carcinoma (P < 0.018 and P < 0.030, respectively). bcl-xS was present at low
      levels in 83% of neoplastic samples and was undetectable in normal tissue.
      Reverse transcriptase-PCR analysis of 74 tumors showed no major correlation with
      clinicopathological parameters or with response to chemotherapy. Only bax and bcl
      xL were correlated with progesterone receptor levels (n = 29, r = +0.44, P <
      0.0189, and r = -0.40, P < 0.035, respectively). No correlation was found with
      estrogen receptor levels or with p53 immunostaining. Our data indicate that the
      regulation of the bcl-2 family of proteins differs between normal and neoplastic
      ovarian tissues. Moreover, the modulation of these genes in ovarian carcinoma is
      different compared to other tissues; therefore, tissue specificity is very
      important in regulation of the bcl-2 family of proteins.

PMID- 9516945
TI  - The role of DNA mismatch repair in drug resistance.
AB  - Loss of DNA mismatch repair (MMR) has been observed in a variety of human
      cancers. In addition to predisposing to oncogenesis, loss of MMR activity is of
      concern with respect to the use of chemotherapeutic agents to treat established
      tumors. Loss of MMR results in drug resistance directly by impairing the ability
      of the cell to detect DNA damage and activate apoptosis and indirectly by
      increasing the mutation rate throughout the genome. The MMR proteins are involved
      in mediating the activation of cell cycle checkpoints and apoptosis in response
      to DNA damage. MMR-deficient cells have been reported to be resistant to the
      methylating agents procarbazine and temozolomide, the alkylating agent busulfan,
      the platinum-containing drugs cisplatin and carboplatin, the antimetabolite 6
      thioguanine, and the topoisomerase II inhibitors etoposide and doxorubicin. In
      the case of cisplatin, busulfan, temozolomide, and procarbazine, the degree of
      resistance has been shown to be sufficient to produce a large difference in
      clinical responsiveness in vivo in tumor model systems. The available preclinical
      data suggest that tumors that contain a significant fraction of cells deficient
      in MMR will demonstrate reduced responsiveness to specific drugs. The challenge
      now is to assess the clinical significance of the presence of deficient cells in
      tumors and to discover drugs that retain activity against MMR-deficient cells.

PMID- 9516946
TI  - HER-2 expression and response to tamoxifen in estrogen receptor-positive breast
      cancer: a Southwest Oncology Group Study.
AB  - HER-2/neu is a growth factor receptor, the expression of which has been
      associated with a more aggressive breast tumor biology and resistance to some
      types of chemotherapy. Preliminary laboratory and clinical data have led to
      claims that HER-2/neu expression is also associated with resistance to tamoxifen.
      Therefore, to test the hypothesis that HER-2/neu expression is associated with a
      poorer response to tamoxifen, a shorter time to treatment failure (TTF), and
      worse survival in estrogen receptor (ER)-positive metastatic breast cancer, we
      examined 205 paraffin-embedded blocks of tumors from patients enrolled on
      Southwest Oncology Group 8228 for HER-2/neu expression. Tumors were ER positive
      (ER level > 3 fmol/mg cytosolic protein in either primary tumors or metastases),
      and patients had not received any prior therapy for metastatic disease. All
      patients were treated with daily tamoxifen. The study began in 1982, and median
      follow-up of patients who are still alive is now 9 years. Membrane staining for
      HER-2/neu was evaluated by immunohistochemistry using antibody TAB 250 and was
      scored according to the proportion of cells staining positive; tumors were deemed
      positive if > 1% of the cells stained for HER-2/neu. HER-2/neu positivity was
      associated with lower ER values (P = 0.04) and low bcl-2 (P = 0.01). HER-2/neu
      positivity was not significantly associated with response rate (negative versus
      positive, 57 versus 54%; P = 0.67), TTF (median, 8 versus 6 months; P = 0.15), or
      survival (median, 31 versus 29 months; P = 0.36). There was also no significant
      evidence of a progressive relationship between an increasing proportion of cells
      expressing HER-2/neu and a shorter TTF or survival. HER-2/neu expression in ER
      positive metastatic breast cancer is not significantly associated with a poorer
      response to tamoxifen or a more aggressive clinical course. Earlier suggestions
      to the contrary may have been due to failure to rigorously exclude ER-negative
      tumors, which are much less likely to respond to tamoxifen and more likely to
      have high HER-2/neu levels.

PMID- 9516947
TI  - Asynchronous modulation of transforming growth factor alpha and epidermal growth
      factor receptor protein expression in progression of premalignant lesions to head
      and neck squamous cell carcinoma.
AB  - The development of head and neck squamous cell carcinoma occurs as a result of
      the accumulation of genotypic and phenotypic alterations in the upper
      aerodigestive tract mucosa. Up-regulation of epidermal growth factor receptor
      (EGFR) and its ligand, transforming growth factor alpha (TGF-alpha), have been
      identified previously as early events in head and neck carcinogenesis. To
      determine the timing of increased TGF-alpha and EGFR protein expression in the
      development of head and neck cancer, we examined progressive mucosal dysplasias
      from three distinct and complimentary patient groups: (a) samples from patients
      with lesions demonstrating different degrees of dysplasia (n = 22) compared with
      mucosa samples from gender and age-matched controls (n = 8); (b) patients with
      lesions demonstrating different degrees of dysplasia at a single time point (n =
      3); and (c) patients who progressed over several years to invasive cancer at the
      site of dysplasia (n = 7). Immunohistochemical analysis with monoclonal
      antibodies specific for TGF-alpha and EGFR were used to detect protein expression
      in all specimens. Protein levels were further quantitated using a computerized
      image analysis system. In all three groups, we found that TGF-alpha protein
      levels were elevated in mild dysplasia compared with control normal mucosa and
      were not further modulated with increasing degrees of dysplasia. In contrast,
      EGFR levels were relatively low in mild dysplasia and increased with higher
      degrees of dysplasia. These findings indicate that up-regulation of TGF-alpha and
      EGFR are distinct events both chronologically and, possibly, mechanistically in
      the pathogenesis of head and neck squamous cell carcinoma.

PMID- 9516948
TI  - CD44 expression in the stromal matrix of colorectal cancer: association with
      prognosis.
AB  - CD44, a cell hyaluronate receptor, is implicated in the metastatic behavior of
      some cancer cells. This study analyzed CD44 expression in topographic tissue
      sites of colorectal cancers to determine its association with patient survival
      and clinicopathological characteristics. Immunohistochemical localization of the
      core CD44 and the v6 splice variant domains was examined by use of paraffin-fixed
      sections from 133 stage II or III colorectal cancers that previously had been
      evaluated for other diagnostic markers. Expression in malignant epithelium,
      stromal matrix, and stromal cells was compared to patient survival by univariate,
      multivariate, and bootstrap (reproducibility) analysis. Core CD44 staining was
      present in the malignant epithelium of 85% of tumors, the stromal matrix of 90%,
      and the stromal cells of 98%. The v6 splice variant domain was present in the
      epithelium of 77% of tumors but was less frequent in the stromal matrix (12%; P <
      0.001) and stromal cells (17%; P < 0.001). Absence of core CD44 immunoreactivity
      in the stromal matrix was associated with increased death rate (hazard ratio,
      2.4; 95% confidence interval, 1.2-4.8; P = 0.02), making this one of the most
      significant adverse prognostic variables, along with an age of 60 years or older,
      poor differentiation of the cancer, extramural venous invasion, chromosome 18q
      allelic loss, and nonwhite race. This study shows that core CD44 and v6 splice
      variant antigens are differentially expressed in the epithelium and stroma of
      colorectal cancers. A model that includes core CD44 immunoreactivity in stromal
      matrix along with other prognostic factors may improve identification of high
      risk and low-risk patients.

PMID- 9516949
TI  - Expression of intercellular adhesion molecule-1 in invasive breast cancer
      reflects low growth potential, negative lymph node involvement, and good
      prognosis.
AB  - To understand the role of intercellular adhesion molecule-1 (ICAM-1) in tumor
      progression in the host, we examined ICAM-1 expression in breast cancer by
      immunohistochemistry. This study included 274 female patients with invasive
      breast cancer, with a median follow-up of 98 months. The molecule was identified
      in formalin-fixed, paraffin-embedded primary tumors, and the relationship to
      clinicopathological factors and prognosis was analyzed. ICAM-1 expression
      occurred in 50.3% of patients. ICAM-1 expression had negative correlation to
      tumor size (P = 0.003), lymph node metastasis (P < 0.0001), tumor infiltration (P
      = 0.003), nuclear pleomorphism (P = 0.004), and nuclear grade (P = 0.042).
      Patients with ICAM-1-positive tumors had better relapse-free and overall survival
      than those with negative tumors (P < 0.0001 and P = 0.0003, respectively). These
      results suggest that expression of ICAM-1 on cancer cells might have a role as a
      suppressor of tumor progression under the host immune surveillance system.

PMID- 9516950
TI  - Phase II study of suramin plus aminoglutethimide in two cohorts of patients with
      androgen-independent prostate cancer: simultaneous antiandrogen withdrawal and
      prior antiandrogen withdrawal.
AB  - Management of prostate cancer progression after failure of initial hormonal
      therapy is controversial. Recently, the activity of the simple discontinuation of
      antiandrogen therapy has been established by several groups, as well as the
      enhanced activity when combined with adrenal suppression (i.e., aminoglutethimide
      and hydrocortisone). Furthermore, suramin has generated considerable interest
      following reports of response rates ranging from 17 to 70%. More recently,
      suramin response rates of 18 and 22% have been reported when the potential
      confounding variables of flutamide withdrawal and hydrocortisone were
      prospectively controlled. On the basis of the activity of combining
      aminoglutethimide with flutamide withdrawal, we designed a protocol in which
      suramin was combined with aminoglutethimide in two cohorts of patients (those
      with simultaneous antiandrogen withdrawal compared to those who had previously
      discontinued antiandrogen therapy). Eighty-one evaluable patients were enrolled
      in this study between June 1992 and November 1994. Patients were a priori divided
      into two cohorts, those receiving prior antiandrogen withdrawal (n = 56) and
      those receiving simultaneous antiandrogen withdrawal (n = 25) at the time the
      patients were enrolled into the trial. For the group that discontinued
      antiandrogen prior to enrolling in therapy, the partial response rate (> 50%
      decline in PSA for > 4 weeks) was 14.2%, whereas the partial response was 44% for
      those patients who discontinued their antiandrogen at the time of starting
      suramin and aminoglutethimide. The median time to progression was 3.9 months in
      patients failing prior antiandrogen withdrawal and 5.5 months in those patients
      having concomitant antiandrogen withdrawal (P = 0.36 for the overall difference).
      The progression-free survival estimate at 1 year for patients having prior
      antiandrogen withdrawal was 19.8% [95% confidence interval (CI), 11-32.9%]. For
      those patients who experienced antiandrogen withdrawal simultaneous with the
      treatment, the progression-free survival estimates at 1 and 2 years were 27.1
      (95% CI, 13.2-47.6%) and 4.5% (95% CI, 0.8-21.6%). The median survival time for
      those patients having prior antiandrogen withdrawal was 14.2 months, whereas the
      median survival was 21.9 months for those having concomitant antiandrogen
      withdrawal (P = 0.029 for the overall difference). In conclusion, the partial
      response rate of 44% for those who had concomitant flutamide withdrawal with
      adrenal suppression was consistent with that of other reports using a similar
      maneuver. Although this study was not randomized and thus we should not over
      interpret the results, flutamide withdrawal plus adrenal suppression appears to
      have greater activity than flutamide withdrawal alone. Furthermore, these data
      suggest that suramin adds little to the response rate observed for other adrenal
      suppressive agents in the presence of antiandrogen withdrawal. This
      interpretation is in agreement with those studies controlling for adrenal
      suppression and flutamide withdrawal prior to suramin administration, which noted
      modest activity of short duration. Given that antiandrogen withdrawal is now
      accepted as an active maneuver for a subset of patients progressing after maximum
      androgen blockade, we propose that future trials attempting to maximize response
      rates incorporate this maneuver whenever possible into prospectively designed
      regimens.

PMID- 9516951
TI  - Pharmacokinetic and pharmacodynamic studies of fludarabine and cytosine
      arabinoside administered as loading boluses followed by continuous infusions
      after a phase I/II study in pediatric patients with relapsed leukemias. The
      Children's Cancer Group.
AB  - The sequential administration of fludarabine followed by cytosine arabinoside
      (ara-C) has demonstrated significant synergistic effects against the CEM human
      leukemic cell line. This in vitro synergism was investigated in a Phase I trial
      in pediatric patients with relapsed acute leukemia. The optimum concentrations of
      9-beta-D-arabinofuranosyl 2-fluoroadenine and ara-C necessary to achieve
      significant drug synergism from in vitro studies were between 10 and 20 microM.
      Fludarabine was infused at a dose to attain a target plasma concentration of 10
      microM for 48 h, followed by a continuous infusion of escalated ara-C doses to
      maintain plasma ara-C concentrations of 10, 12.5, 15, or 17.5 microM for 72 h.
      Thirteen patients with acute lymphocytic leukemia and 18 with acute myelocytic
      leukemia were entered into the study, 30 of whom were clinically evaluable for
      toxicity. Pharmacokinetic and pharmacodynamic studies were performed on specimens
      from 20 patients. The optimal 9-beta-D-arabinofuranosyl 2-fluoroadenine and ara-C
      concentrations in plasma were easily achieved after continuous infusion regimens
      of both drugs. Cellular ara-CTP is augmented 5-8-fold in leukemic cells from
      patients receiving fludarabine phosphate treatment followed by ara-C. The maximum
      tolerated plasma concentrations for this combination regimen was 10 microM
      fludarabine for 48 h followed by 72 h of 15 microM ara-C, which were achieved at
      dose level 3. A significant number of responses were also seen. Nine of 18
      evaluable patients (50%) with acute myelocytic leukemia achieved complete or
      partial responses, and 3 of 9 evaluable patients with acute lymphocytic leukemia
      achieved complete or partial responses. Fludarabine and ara-C successfully
      eradicated bone marrow disease in 16 of 27 patients (59%), 23 patients of which
      had been treated previously with high-dose ara-C. These results verified the
      synergistic effect fludarabine exhibited in augmenting ara-CTP concentrations in
      patients' leukemic blasts, thus improving the clinical response in relapsed
      pediatric leukemias.

PMID- 9516952
TI  - A phase I and pharmacokinetic study of tallimustine [PNU 152241 (FCE 24517)] in
      patients with advanced cancer.
AB  - Tallimustine [PNU 152241 (FCE 24517)] is a synthetic derivative of the DNA minor
      groove binder distamycin A, in which the NH2-terminal formyl group is substituted
      by benzoyl mustard. In this Phase I clinical trial, patients with advanced solid
      tumors received i.v. bolus injections of tallimustine daily for 3 consecutive
      days. Patients were treated at six dosage levels of 33.3 micrograms/m2/day to 250
      micrograms/m2/day for 3 consecutive days, with courses of therapy repeated every
      28 days. Detailed pharmacokinetic blood sampling was performed during the first 3
      days of the first course of tallimustine. The plasma samples were analyzed by
      high-performance liquid chromatography with UV detection. Forty-eight eligible
      patients were treated at all six dosage levels. The dominant dose-related
      toxicity of tallimustine was neutropenia, becoming dose limiting at 250
      micrograms/m2/day. At this dosage level, one patient experienced febrile
      neutropenia, and a second patient died on study of indeterminate cause.
      Thrombocytopenia was not observed, and only 10 patients developed anemia < 8.0
      gm/dl. Sporadic elevation of liver enzymes or bilirubin was observed but was not
      dose related. Pharmacokinetic analysis gave reliable results for 33 patients. For
      most patients, analysis of the data best fit a three-exponential model. Dose
      related increases in areas under the concentration-time curve and end-of-infusion
      concentrations were observed. There was no significant plasma accumulation of
      tallimustine over the 3 days of administration. The terminal half-life of
      tallimustine in individual patients ranged from 6.83 to 39.02 h following the
      last dose. In summary, the recommended Phase II dosage for tallimustine is 200
      micrograms/m2/day for 3 consecutive days every 28 days. Neutropenia is the
      principal toxicity of this agent at this dosage and schedule.

PMID- 9516953
TI  - Treatment of metastatic bone pain with tin-117m Stannic
      diethylenetriaminepentaacetic acid: a phase I/II clinical study.
AB  - The physical characteristics of Sn-117m combined with the biodistribution of the
      compound tin-117m (Stannic, 4+) diethylenetriaminepentaacetic acid (Sn-117m DTPA)
      suggest that it should be an excellent agent for the palliation of pain from bony
      metastases. Prior work has established the dosimetry and the safety for the
      material in human beings. The presence of low-energy conversion electrons should
      result in the relative sparing of the bone marrow while delivering a high
      radiation dose to sites of bony metastatic disease. Forty-seven patients with
      painful bone metastases from various malignancies were treated with Sn-117m DTPA.
      The patients were assigned to five different dose levels ranging from 2.64 to
      10.58 MBq (71-286 microCi) per kg of body weight. Follow-up included review of
      pain diaries, performance scores, analgesic requirements, blood chemistries, and
      hematological assessment. Three patients received a second treatment. There was
      an overall response rate for relief of pain of 75% (range, 60-83%) in the 40
      treatments that could be evaluated. No correlation was apparent in this limited
      series between response rate and the five dose levels used. The relief was
      complete in 12 patients (30%). The time to onset of pain relief was 19 +/- 15
      days with doses < or = 5.29 MBq/kg and 5 +/- 3 days with doses > or = 6.61
      MBq/kg. Myelotoxicity was minimal, with only one patient having a marginal grade
      3 WBC toxicity. On the basis of our data, Sn-117m DTPA should be an effective and
      safe radiopharmaceutical for palliation of painful bony metastases. A large-scale
      trial is warranted to evaluate it in comparison to other similar agents.

PMID- 9516954
TI  - Cranial irradiation and permeability of blood-brain barrier to cytosine
      arabinoside in children with acute leukemia.
AB  - Cranial irradiation (CI) is an effective way to prevent central nervous system
      (CNS) leukemia in children with acute leukemia (AL). However, it is still unclear
      whether the antileukemic effect of CI is mediated by alteration of blood-brain
      barrier (BBB) permeability and consequent increased levels of systemically
      administered drugs or whether it simply results from a direct cytolytic effect on
      leukemic cells in the meninges at diagnosis. We evaluated the influence of CI on
      BBB permeability to 1-beta-D-arabinofuranosylcytosine (ara-C) in 23 children with
      AL undergoing CI for CNS leukemia prophylaxis. CI was administered at 18 Gy (16
      patients) and 24 Gy (7 patients). ara-C levels were measured in cerebrospinal
      fluid (CSF) and plasma before, during, and after CI. Two doses were evaluated: 75
      mg/m2/day (12 patients) and 480 mg/m2/day (11 patients). CSF and plasma ara-C
      levels were measured when steady state was achieved. CSF:plasma ratios, obtained
      before, during, and after CI, were compared by an ANOVA model for repeated
      measures and by Tukey's test. At the 75-mg/m2/day dose, the mean values of ara-C
      CSF:plasma ratios before, during, and after CI were 0.20, 0.27, and 0.27,
      respectively. At the 480-mg/m2/day dose, the mean CSF:plasma ratios before,
      during, and after CI were 0.09, 0.12, and 0.13, respectively. No significant
      differences were observed when CSF:plasma ratios were compared before and during,
      during and after, and before and after CI. Our results indicate that CI at the
      doses used for CNS prophylaxis in AL does not significantly alter the BBB as far
      as ara-C is concerned.

PMID- 9516955
TI  - Pilot study of subcutaneous recombinant human interleukin 12 in metastatic
      melanoma.
AB  - The aim of this study was to evaluate the safety profile of s.c. administered
      recombinant human interleukin 12 (rHuIL-12). Pharmacokinetics and
      pharmacodynamics of rHuIL-12 and any evidence of antitumor effect were also
      considered. Ten pretreated patients with progressive metastatic melanoma were
      enrolled in this pilot study. Patients received a fixed dose of rHuIL-12 (0.5
      microgram/kg) for two identical 28-day cycles, with injections given on days 1,
      8, and 15 of each cycle. In case of any evidence of response or disease
      stabilization, the treatment was continued for two further 28-day cycles.
      Toxicity mainly consisted of a flu-like syndrome. Transient increases in
      transaminasemia (6 of 10 patients) and triglyceridemia (8 of 10 patients) were
      observed. Peak serum IL-12 levels were reached 8-12 h after the first injection
      in all patients; no serum IL-12 was detectable in 6 of 9 evaluable patients after
      the last injection of the second cycle. No antibody response to rHuIL-12 could be
      detected in any of the patients. A marked, transient reduction in circulating
      CD8+ and CD16+ lymphocytes and neutrophils was observed after the first
      administration and high levels of serum IFN-gamma and IL-10 were detected in all
      patients within 24-48 h. Tumor shrinkage, not reaching partial or complete
      remission, involved the regression of s.c. nodules (2 of 3 patients), superficial
      adenopathies (1 of 3 patients), and hepatic metastases (1 of 3 patients);
      regressions were detected after the first cycle of treatment and were maintained
      in spite of progression at different sites. s.c. rHuIL-12 treatment was well
      tolerated and had marked effects on immune parameters and potential antitumor
      activity.

PMID- 9516956
TI  - Apoptotic tumor cell death induced by estramustine in patients with malignant
      glioma.
AB  - Estramustine phosphate (EMP), a cytotoxic drug used in the treatment of prostatic
      carcinoma, is metabolized and exerts specific cytotoxic effects in malignant
      glioma in vitro and in vivo. In the present study, we have evaluated the
      cytotoxic effect of EMP in the clinical situation with regard to appearance of
      DNA damage and its correlation to the uptake of estramustine (EaM) in human
      malignant astrocytoma tissue. Ten patients were given 280 mg of EMP p.o. 12 h
      before surgery. Specimens from brain tumor tissue were collected during surgery
      and used for detection of fragmented DNA, a hallmark of apoptosis, with in situ
      end labeling (ISEL) and agarose gel techniques. The main metabolite of EMP in
      glioma tissue, EaM, was analyzed with gas chromatography. It was demonstrated
      that EMP induced clusters of ISEL-positive tumor cells and fragmentation of DNA
      on agarose gels in patients treated with EMP. In the same patients, a significant
      uptake of EaM in tumor tissue was demonstrated. In control patients, who were not
      treated with EMP, and in two EMP-treated patients with no uptake of EaM, no signs
      of fragmented DNA and only a few scattered ISEL-positive cells were seen in the
      tumor tissue. Signs of apoptosis were also seen in two different experimental
      models, i.e., in vitro cell cultures of rat glioma cells and an in vivo rat
      glioma model. It is suggested that EaM can induce apoptosis by a direct effect on
      a subpopulation of glioma cells in human brain tumors in the clinical situation.

PMID- 9516957
TI  - Detection of germ cell tumor cells in apheresis products using polymerase chain
      reaction.
AB  - The contamination of apheresis products with tumor cells was evaluated in
      patients undergoing autologous peripheral blood stem cell transplantation for
      germ cell tumors. A blinded, retrospective analysis was performed on 63 apheresis
      products from 28 patients using the PCR and primers for beta human chorionic
      gonadotropin (beta-HCG). Of the 20 patients with beta-HCG-secreting tumors, 8
      apheresis products from 7 patients were PCR positive. PCR was negative in the 8
      patients whose tumors did not secrete beta-HCG. Twenty-two apheresis products
      from patients with lymphoma and breast cancer were negative for beta-HCG
      expression. Evaluating the 20 patients with beta-HCG-secreting tumors, 100% of
      PCR-positive patients had elevated serum beta-HCG at the time of apheresis
      compared to 46.2% of PCR-negative patients (P = 0.04). A positive PCR was also
      associated with a higher serum beta-HCG at diagnosis (P = 0.03). Patients
      receiving a PCR-positive product had a higher relapse rate (85.7 versus 61.5%)
      and were more likely to have visceral metastasis (100 versus 61.5%), although the
      numbers did not reach statistical significance (P = 0.35 and 0.11, respectively).
      The finding of beta-HCG mRNA in apheresis products strongly suggests the presence
      of circulating tumor cells in a significant number of germ cell patients
      undergoing autologous transplantation. This assay may be useful in monitoring
      attempts at tumor cell depletion and in developing improved prognostic models for
      assessing risk of relapse after transplantation.

PMID- 9516958
TI  - Preclinical evaluation of 5-iodo-2-pyrimidinone-2'-deoxyribose as a prodrug for 5
      iodo-2'-deoxyuridine-mediated radiosensitization in mouse and human tissues.
AB  - We reported previously that p.o. administered 5-iodo-2-pyrimidinone-2'
      deoxyribose (IPdR) was efficiently converted to 5-iodo-2'-deoxyuridine (IUdR) in
      athymic mice (T. J. Kinsella et al., Cancer Res., 54: 2695-2700, 1994). Here, we
      further evaluate IPdR metabolism, systemic toxicity, and percentage DNA
      incorporation in athymic mouse normal tissues and a human colon cancer xenograft
      (HT29) using higher p.o. doses of IPdR. These data are compared to results using
      a continuous infusion of IUdR at the maximum tolerable dose. We also evaluate
      IPdR metabolism in cytosolic extracts from normal human liver, normal human
      intestine, and human colorectal cancer specimens. Athymic mice tolerated a daily
      p.o. bolus of up to 2 g/kg IPdR for 6 days with minimal host toxicity (< or = 10%
      body weight loss). There was rapid conversion of IPdR to IUdR, with peak plasma
      levels of IUdR of 40-75 microM at 10 min following a p.o. IPdR bolus of 250-1500
      mg/kg. The percentage IUdR-DNA in the HT29 s.c. human tumor xenografts increased
      1.5 times (2.3-3.6%) with IPdR doses above 1 g/kg/day for 6 days, whereas the
      percentage IUdR-DNA incorporation in two proliferating normal tissues (4-4.5% in
      intestine; 1.6-2.2% in bone marrow) and a quiescent normal tissue (< or = 1% in
      liver) showed < 1.5-fold increases with the IPdR dose escalation between 1-2
      g/kg/day for 6 days. In contrast, using a continuous infusion of IUdR at 100
      mg/kg/day, significant systemic toxicity (> 20% body weight loss) was found by
      day 6 of the infusion. Steady-state plasma IUdR levels were 1.0-1.2 microM during
      the 6-day infusion, and percentage IUdR-DNA incorporations of 2.3, 8, 6, and 1%
      were measured in s.c. tumors, normal intestine, normal bone marrow, and normal
      liver, respectively, following the 6-day infusion. Thus, the p.o. IPdR schedule
      has an improved therapeutic index, based on percentage IUdR-DNA incorporation in
      normal and tumor tissues, compared to continuous infusion IUdR at the maximum
      tolerable dose in athymic mice with this human tumor xenograft. Additionally, a
      tumor regrowth assay to assess the radiation response of HT29 s.c. xenografts
      showed a 1.5-fold enhancement (time to regrow to 300% initial tumor volume) with
      IPdR (1000 mg/kg/day for 6 days) plus fractionated irradiation (XRT; 2 Gy/day for
      4 days), compared to XRT (2 Gy/day for 4 days) alone. No enhancement in the
      radiation response of HT29 s.c. xenografts was found with continuous infusion
      IUdR (100 mg/kg/day for 6 days) plus XRT (2 Gy/day for 4 days), compared to XRT
      alone. Using cytosolic extracts from normal human liver specimens, we found a
      rapid (15-min) conversion of IPdR to IUdR. Coincubation of liver cytosol with
      IPdR and allopurinol, an inhibitor of xanthine oxidase, had no inhibitory effect
      on IPdR metabolism, whereas coincubation with IPdR and isovanillin or menadione,
      analogue substrates for aldehyde oxidase, effectively reduced the amount of IPdR
      oxidized to IUdR. Significantly less metabolism of IPdR to IUdR was seen in
      cytosolic extracts from normal human intestine specimens, and no metabolism of
      IPdR was found in cytosolic extracts from colorectal liver metastases in two
      patients and from the HT29 human colon cancer xenografts in athymic mice. These
      additional data indicate that IPdR has the potential for clinical use as a p.o.
      prodrug for IUdR-mediated radiosensitization of resistant human cancers.

PMID- 9516959
TI  - Doxorubicin entrapped in sterically stabilized liposomes: effects on bacterial
      blood clearance capacity of the mononuclear phagocyte system.
AB  - The introduction of long-circulating liposomes sterically stabilized by surface
      coating with polyethylene glycol has expanded the potential for drug targeting to
      tumors. In recent clinical studies, evidence of significant antitumor activity
      has been obtained with the industrially prepared formulation of long-circulating
      polyethylene glycol-coated liposomes containing doxorubicin, referred to as
      DOXIL. Previous studies performed in rats showed that doxorubicin-containing
      liposomes can exert major toxic effects on the liver macrophage population for a
      considerable period of time; a strong impairment of phagocytic function and even
      a substantial depletion of the liver macrophage populations were observed. In the
      present study, the phagocytic function of the mononuclear phagocyte system (MPS)
      after administration of DOXIL at a clinically relevant dosage schedule was
      evaluated in rats. Phagocytic function of the MPS was assessed by determining
      bacterial blood clearance capacity. The observations reported herein show that
      DOXIL is fairly well tolerated regarding bacterial blood clearance capacity of
      the MPS when administered in a regimen that resembles the clinical setting
      closely. This outcome has important implications with regard to the clinical
      utility of the liposomal drug, especially in the restricted context of
      immunocompromised cancer patients who easily develop systemic infections and
      should not be confronted with a therapy-induced reduction of the bacterial blood
      clearance capacity of the MPS.

PMID- 9516960
TI  - 6-Aminonicotinamide sensitizes human tumor cell lines to cisplatin.
AB  - The nicotinamide analogue 6-aminonicotinamide (6AN) is presently undergoing
      evaluation as a potential modulator of the action of various antineoplastic
      treatments. Most previous studies of this agent have focused on a three-drug
      regimen of chemical modulators that includes 6AN. In the present study, the
      effect of single-agent 6AN on the efficacy of selected antineoplastic drugs was
      assessed in vitro. Colony-forming assays using human tumor cell lines
      demonstrated that pretreatment with 30-250 microM 6AN for 18 h resulted in
      increased sensitivity to the DNA cross-linking agent cisplatin, with 6-, 11-, and
      17-fold decreases in the cisplatin dose that diminishes colony formation by 90%
      being observed in K562 leukemia cells, A549 non-small cell lung cancer cells, and
      T98G glioblastoma cells, respectively. Morphological examination revealed
      increased numbers of apoptotic cells after treatment with 6AN and cisplatin
      compared to cisplatin alone. 6AN also sensitized cells to melphalan and nitrogen
      mustard but not to chlorambucil, 4-hydroperoxycyclophosphamide, etoposide, or
      daunorubicin. In additional studies undertaken to elucidate the mechanism
      underlying the sensitization to cisplatin, atomic absorption spectroscopy
      revealed that 6AN had no effect on the rate of removal of platinum (Pt) adducts
      from DNA. Instead, 6AN treatment was accompanied by an increase in Pt-DNA adducts
      that paralleled the degree of sensitization. This effect was not attributable to
      6AN-induced decreases in glutathione or NAD+, because other agents that depleted
      these detoxification cofactors (buthionine sulfoximine and 3-acetylpyridine,
      respectively) did not increase Pt-DNA adducts. On the contrary, 6AN treatment
      increased cellular accumulation of cisplatin. Further experiments revealed that
      6AN was metabolized to 6-aminonicotinamide adenine dinucleotide (6ANAD+).
      Concurrent administration of nicotinamide and 6AN had minimal effect on cellular
      6AN accumulation but abolished the formation of 6ANAD+, the increase in Pt-DNA
      adducts, and the sensitizing effect of 6AN in clonogenic assays. These
      observations identify 6AN as a potential modulator of cisplatin sensitivity and
      suggest that the 6AN metabolite 6ANAD+ exerts this effect by increasing cisplatin
      accumulation and subsequent formation of Pt-DNA adducts.

PMID- 9516961
TI  - Characterization of 5-oxo-L-prolinase in normal and tumor tissues of humans and
      rats: a potential new target for biochemical modulation of glutathione.
AB  - 5-Oxo-L-prolinase (5-OPase) is an enzyme of the gamma-glutamyl cycle involved in
      the synthesis and metabolism of glutathione (GSH), which is known to protect
      cells from the cytotoxic effects of chemotherapy and radiation. Previous studies
      on rats have shown that administration of the cysteine prodrug L-2
      oxothiazolidine-4-carboxylate, a 5-oxo-L-proline analogue that is metabolized by
      5-OPase, preferentially increases the GSH content of normal tissues while
      paradoxically decreasing it in the tumor and results in an enhanced in vivo tumor
      response to the anticancer drug melphalan. These observations initiated the
      present study of 5-OPase in experimental models and clinical specimens to
      investigate the potential role of this enzyme in the selective modulation of GSH
      in normal and tumor tissues. First, 5-OPase activity was measured in tissues of
      tumor-bearing rats, in the peripheral mononuclear cells of normal human subjects,
      and in surgically resected tumor and the adjacent normal tissues from patients.
      We found that the activity of 5-OPase in human kidney, liver, and lung is
      significantly lower than that found in rats. Second, we have raised a polyclonal
      IgG anti-5-OPase antibody by immunizing rabbits with purified 5-OPase from rat
      kidney. This antibody has very high affinity (shown by immunoprecipitation) and
      specificity (shown by Western blot) and cross-reacts with human 5-OPase (shown by
      Western blot and immunohistochemistry). It was then used to examine the
      distribution of 5-OPase in paired normal and neoplastic human specimens using
      Western blot and immunohistochemistry. Examination of paired normal and
      neoplastic tissues of stomach and lung revealed a significantly lower level of 5
      OPase in tumor tissues than in the paired normal tissues. In colon tissues, there
      is no significant difference in 5-OPase level between the normal and tumor
      tissues. These findings could have implications for both carcinogenesis and
      therapy.

PMID- 9516962
TI  - Bladder tissue uptake of mitomycin C during intravesical therapy is linear with
      drug concentration in urine.
AB  - The design of an ongoing Phase III study of intravesical mitomycin C therapy to
      treat bladder cancer is partly based on the assumption that drug penetration into
      bladder tissue is linearly related to drug concentration. The present study was
      designed to (a) test this assumption and (b) to compare drug concentrations in
      tumor and adjacent normal tissues in human bladders. We previously reported the
      uptake kinetics of a 20-mg dose in dog and human bladders (M. G. Wientjes et al.,
      Cancer Res., 51: 4347-4354, 1991, and Cancer Res., 53: 3314-3320, 1993). The
      present study used a 40 mg/20 ml dose. Serial blood and urine samples were taken
      from dogs during the 120-min instillation. Bladder tissues were harvested from
      dogs and patients at the end of instillation. A comparison of the results of the
      present and previous studies indicates identical tissue penetration kinetic
      parameters in dogs for the two doses, i.e., a approximately 30-fold concentration
      drop across the urothelium and a half-width of approximately 500 microns. In
      addition, the average tissue concentration in dog and human bladders attained
      with the 40-mg dose (8.77 micrograms/g in dogs and 7.55 micrograms/g in humans)
      was about twice that achieved with the 20-mg dose (4.33 micrograms/g in dogs and
      3.91 micrograms/g in humans). In dogs, the plasma concentration of MMC reached a
      steady state within 10 min; the mean maximal plasma concentration was 8.5 ng/ml.
      This plasma concentration is indistinguishable from the concentration derived
      from the 20-mg dose and indicates a minimal systemic exposure even at the higher
      dose. The average MMC concentration in tumor-bearing tissues was about 40% higher
      than the concentration in adjacent normal tissues (P = 0.01). In conclusion, the
      linear relationship between drug uptake in bladder tissues and drug concentration
      in urine supports the assumption used in the design of the ongoing Phase III
      clinical trial.

PMID- 9516964
TI  - Modulation of cancer chemotherapy by green tea.
AB  - Biochemical modulation has played an important role in the development of cancer
      chemotherapy. We have directed our attention to the intake of common beverages
      and investigated the effects of green tea and tea components on the antitumor
      activity of doxorubicin. We carried out the combined treatment of toxorubicin and
      green tea on Ehrlich ascites carcinoma tumor-bearing mice. The oral
      administration of green tea enhanced 2.5-fold the inhibitory effects of
      doxorubicin on tumor growth. The Doxorubicin concentration in the tumor was
      increased by the combination of green tea with doxorubicin. In contrast, the
      increase in doxorubicin concentration was not observed in normal tissues after
      green tea combination. Furthermore, the enhancement of antitumor activity of
      doxorubicin induced by green tea was observed in M5076 ovarian sarcoma, which has
      low sensitivity to doxorubicin. These results suggest that drinking green tea can
      encourage cancer chemotherapy and may improve the quality of life of clinical
      patients.

PMID- 9516963
TI  - Selective sensitization to DNA-damaging agents in a human rhabdomyosarcoma cell
      line with inducible wild-type p53 overexpression.
AB  - Drug-induced cytotoxicity or apoptosis may be influenced by the expression of the
      p53 tumor suppressor gene and by the specific oncogene expressed, which may
      dictate the threshold at which a cytotoxic response may by induced. The objective
      of the study was to elucidate how DNA-damaging agents with different mechanisms
      of action were sensitized in the context of expression of the Pax3/FKHR fusion
      protein, a transformation event unique to alveolar rhabdomyosarcomas (ARMSs), and
      wild-type p53 (wtp53). A wtp53 cDNA was subcloned into the pGRE5-2/EBV vector
      with dexamethasone-inducible overexpression and transfected into Rh30 ARMS cells
      that express Pax3/FKHR and a mutant p53 phenotype. Following dexamethasone
      induction of wtp53 overexpression in a derived clone (Cl.#27), growth was slowed,
      and cells accumulated in G1. Functional wtp53 activity was demonstrated by
      selective transactivation of p50-2, a wtp53 chloramphenicol acetyltransferase
      reporter construct, and by up-regulated expression of endogenous p21Waf1. Data
      demonstrated p53-dependent sensitization (> or = 4-fold) to bleomycin,
      actinomycin D, and 5-fluorouracil and considerably less p53-dependence (< or = 2
      fold) for doxorubicin, topotecan, etoposide, and cisplatin in Cl.#27 compared to
      an equivalent clone containing the pGRE5-EBV vector alone (VC#3). Data
      demonstrate that ARMS cells show a selective sensitization to DNA-damaging agents
      when wtp53 is overexpressed. The cytotoxic activity of agents that are not
      potentiated substantially must, therefore, depend upon p53-independent factors
      that relate to the mechanism of drug action.

PMID- 9516965
TI  - A sensitive and specific radioimmunoassay for LY309887, a potent inhibitor of
      glycinamide ribonucleotide formyltransferase.
AB  - LY309887, a reduced analogue of folic acid, is a potent inhibitor of glycinamide
      ribonucleotide formyltransferase and possesses a broad spectrum of antitumor
      activity. During preclinical studies using supplementation with oral folic acid,
      this second-generation inhibitor displayed both the desired safety profile and
      the pharmacology to warrant clinical investigation. A sensitive analytical method
      was needed to assess the pharmacokinetics of LY309887 due to the low doses
      planned for Phase I studies and the potential for low concentrations in plasma
      long after i.v. administration. We therefore undertook the development of a
      competitive RIA. A highly specific antiserum was raised in rabbits following
      immunization with LY309887 coupled to BSA. A RIA tracer was prepared by
      radioiodination of compound 389753, the adduct of LY309887 with p-tyramine. We
      developed a competitive-binding RIA procedure and used superparamagnetic
      particles coated with goat antirabbit IgG as a method for separating the bound
      and free forms of LY309887. The RIA is sensitive (0.5 ng/ml in serum and 25 ng/ml
      in urine), specific (negligible interference from endogenous folates), and
      reproducible (interassay coefficients of variation ranging from 8.1 to 15.4% and
      7.6 to 8.3% for serum and urine controls, respectively). We used the RIA to
      assess the i.v. pharmacokinetics of LY309887 in both patients with metastatic
      cancer and dogs. The sensitivity of the RIA permitted the demonstration that
      serum concentrations of LY309887 decline in a multiexponential manner with a
      prolonged terminal elimination phase. We conclude that the RIA is a valid method
      for quantifying LY309887 in biological fluids.

PMID- 9516966
TI  - In vivo toxicity and pharmacokinetic features of B43 (anti-CD19)-genistein
      immunoconjugate in nonhuman primates.
AB  - B43 (anti-CD19)-genistein immunoconjugate targets genistein, a naturally
      occurring protein tyrosine kinase-inhibitory isoflavone to the membrane
      associated antiapoptotic CD19-LYN complexes and triggers apoptotic cell death. In
      this preclinical study, the toxicity profiles of B43-genistein as well as
      unconjugated genistein were evaluated in cynomolgus monkeys. B43-genistein and
      genistein were administered either as single bolus injections or daily injections
      for 5-10 consecutive days via the i.v. route to monkeys. Neither genistein nor
      B43-genistein was toxic to cynomolgus monkeys, and no test article-related
      histopathological lesions were found in any of the two genistein-treated or five
      B43-genistein-treated cynomolgus monkeys. B43-genistein showed a favorable
      pharmacokinetics in monkeys, with a plasma half-life of 10-23 h. Plasma samples
      from B43-genistein-treated monkeys elicited potent and CD19 antigenspecific
      antileukemic activity against human CD19+ leukemia cells in vitro. To our
      knowledge, this is the first preclinical toxicity and pharmacokinetic study of a
      tyrosine kinase inhibitor-containing immunoconjugate in nonhuman primates.

PMID- 9516967
TI  - Antitumor activity of actinonin in vitro and in vivo.
AB  - Actinonin, an antibiotic and CD13/aminopeptidase N (APN) inhibitor, has been
      shown to be cytotoxic to tumor cell lines in vitro. We investigated the
      antiproliferative effects of actinonin on human and murine leukemia and lymphoma
      cells. Actinonin inhibited growth of NB4 and HL60 human cell lines and AKR mouse
      leukemia cells in vitro with an IC50 of about 2-5 micrograms/ml. The inhibitory
      effect on CD13-positive cells was not blocked by pretreatment with the anti
      CD13/APN monoclonal antibody F23, which binds with high affinity to the active
      site of CD13/APN and blocks its enzymatic activity. Moreover, F23 alone was not
      inhibitory to CD13-positive cells. Furthermore, a similar inhibitory IC50 of
      actinonin was seen in the CD13-negative cell lines RAJI and DAUDI human lymphoma.
      These data suggest that the inhibitory effect of actinonin is not mediated by
      inhibition of CD13/APN. Cell cycle analysis showed that actinonin induces a G1
      arrest in HL60 and NB4 cells; apoptosis was observed in 20-35% of the cells as
      measured by intracellular flow cytometry. To assess whether these effects could
      be seen in vivo, the effect of actinonin on the syngeneic AKR mouse leukemia
      model was evaluated. Actinonin showed dose-dependent antitumor effects on AKR
      leukemia in vivo, resulting in a survival advantage. In conclusion, apoptosis,
      growth inhibition, and therapeutic effects in vivo are induced by actinonin and
      are not likely to be mediated by CD13/APN.

PMID- 9516968
TI  - Prognostic impact of urokinase-type plasminogen activator (PA), PA inhibitor type
      1, and tissue-type PA antigen levels in node-negative breast cancer: a
      prospective study on multicenter basis.
AB  - Urokinase-type plasminogen activator (u-PA) is a key protease in cancer invasion
      and metastasis. Recent studies demonstrated that u-PA, plasminogen activator
      inhibitor type-1 (PAI-1), and tissue-type plasminogen activator (t-PA) are
      prognostic factors in breast cancer. However, there have been no prospective
      studies of node-negative breast cancer on a multicenter basis. On the other hand,
      some patients, even those with node-negative breast cancer, developed recurrence,
      and only tumor size is available as a predicting factor in this group. Therefore,
      it is necessary to find other prognostic factors in node-negative breast cancer
      to determine suitable adjuvant therapies. Tissue samples in this prospective
      study were obtained from 130 patients with node-negative invasive breast cancer
      who underwent radical operation at four hospitals. The median follow-up was 52.6
      months. u-PA, PAI-1, and t-PA antigen levels were assayed by ELISA kits using the
      cytosolic fractions of tumors. Patients with high u-PA, high PAI-1, or low t-PA
      had significantly higher relapse rates than did those with low u-PA, low PAI-1,
      or high t-PA, respectively, by the Kaplan-Meier method (P = 0.006, 0.032, and
      0.028, respectively). Analyses of the combinations of both u-PA and PAI-1 or both
      u-PA and t-PA showed that the differences in relapse rate between the high- and
      low-risk groups were statistically very significant. In the univariate analysis,
      u-PA, PAI-1, t-PA, progesterone receptor, and tumor size (T3 versus T1) were
      significantly correlated with relapse. However, the multivariate analysis
      revealed that only u-PA (P = 0.023) was an independent prognostic factor. This
      study showed that u-PA was a new significant independent prognostic factor in
      node-negative breast cancer.

PMID- 9516969
TI  - Translocations involving chromosome 12p11-13, methotrexate metabolism, and
      outcome in childhood B-progenitor cell acute lymphoblastic leukemia: a Pediatric
      Oncology Group study.
AB  - Children with B-progenitor cell acute lymphoblastic leukemia whose lymphoblasts
      at diagnosis accumulate high levels of methotrexate (MTX) and MTX polyglutamates
      (MTXPGs) appear to have a good prognosis. This has been attributed to increased
      sensitivity of their blast cells to MTX. However, the proportion of children who
      are cured of B-progenitor cell acute lymphoblastic leukemia exceeds the number
      whose lymphoblasts accumulate high MTXPG levels. We report that lymphoblasts from
      patients with < 50 chromosomes who have translocations that involve the short arm
      of chromosome 12 accumulate low levels of MTXPGs. These patients appear to have
      an excellent survival because none of 14 patients with translocations affecting
      12p has relapsed, 26-79 months following diagnosis.

PMID- 9516970
TI  - Prognostic value of p53 and urokinase-type plasminogen activator in node-negative
      human breast cancers.
AB  - We measured the levels of p53 and urokinase-type plasminogen activator (uPA) in
      634 tumor tissues from 634 different node-negative primary breast cancer patients
      who underwent locoregional surgery in the Center Oscar Lambret between July 1989
      and September 1994. p53 and uPA were assayed using commercially available kits in
      cytosols prepared for estradiol receptor (ER) and progesterone receptor (PgR)
      assays. The optimum clinical thresholds were chosen for prognostic studies: 4
      ng/ml for p53 and 0.5 ng/ml for uPA. p53 was elevated in 13.7% of the tumors, and
      uPA was elevated in 27.5% of the tumors; they were negatively related (chi 2
      test) to ER and PgR and positively related to histoprognostic grading (HPG) and
      tumor diameter. uPA was negatively correlated to ER and PgR, and p53 and uPA were
      positively correlated to each other (P = 0.0001; Spearman test). In the
      prognostic studies, the 316 patients who did not receive adjuvant chemotherapy
      were included to avoid treatment interference; this number corresponds to all of
      the patients operated on between 1989 and 1992. The mean duration of follow-up of
      living patients was 4 years. In overall survival studies, Cox univariate analyses
      demonstrated a prognostic value of p53 (P = 0.011; risk ratio, 1.59), uPA (P =
      0.038; risk ratio, 2.32), PgR, HPG, and tumor diameter. In Cox multivariate
      analyses, only HPG had a statistically significant prognostic value. In relapse
      free survival studies, univariate analyses demonstrated prognostic values of uPA
      (P = 0.0011) and of age, and both parameters retained their prognostic value in
      multivariate analyses (uPA: P = 0.0004). This study demonstrates not only that
      p53 and uPA have prognostic value but also that these two parameters are linked
      to other classical clinical, histological, or biological prognostic parameters,
      as well as to each other. Moreover, because uPA is of prognostic value in
      multivariate relapse-free survival studies, uPA is an important prognostic factor
      in node-negative breast cancer patients.

PMID- 9516971
TI  - Genetic changes and telomerase activity in human renal cell carcinoma.
AB  - Using the sensitive telomeric repeat amplification protocol assay, we detected
      telomerase activity in 26 of 35 (74.3%) renal cell carcinomas analyzed.
      Subdivision of the tumors according to telomerase activity did not reveal an
      obvious association between the presence of telomerase activity and
      histomorphological stage, grade, tumor size, or DNA ploidy. Furthermore, no
      association was found between telomerase activity and a distinct chromosomal
      aberration pattern; namely, loss of genetic material on the short arm of
      chromosome 3. Telomerase activity was also detected in 6 of 35 (17.1%) normal
      corresponding renal tissue samples, which seems interesting in light of the
      supposed biological role of telomerase expression in carcinogenesis.
      Interestingly, telomerase activity was detected in three of the four (75%)
      kidneys bearing non-clear cell tumor types, whereas of the 31 kidneys with clear
      cell carcinomas, telomerase activity was found in only 3 (9.7%) normal tissue
      samples. In addition, the two renal angiomyolipomas and one of the two analyzed
      transitional cell carcinomas of the renal pelvis were telomerase negative.

PMID- 9516972
TI  - TP53 and long-term prognosis in colorectal cancer: mutations in the L3 zinc
      binding domain predict poor survival.
AB  - In a consecutive series of 222 colorectal carcinomas from patients with a median
      follow-up time of 56.8 months (range, 0.5-92.2) treated with surgery, the TP53
      gene was screened for mutations. Exons 5-8 were analyzed using constant
      denaturant gel electrophoresis followed by sequencing, and mutations were found
      in 102 cases (45.9%). Mutations were found more frequently in rectal tumors
      versus other locations (P = 0.029) and in aneuploid compared to diploid tumors (P
      < 0.001). Presence of a TP53 mutation was also significantly associated with
      absence of microsatellite instability (P = 0.028), as well as with loss of
      heterozygosity at 17p13 (P < 0.001). The TP53 mutations in the left-sided and
      rectal tumors were more often transversions than transitions, indicating a
      different etiology in the development of these tumors. The tendency for shorter
      cancer-related survival among patients with mutations in their tumors was only
      statistically significant for patients with left-sided tumors (P = 0.003). All
      patients with mutations affecting the L3 domain of the protein involved in zinc
      binding had a significantly shorter cancer-related survival (P = 0.036),
      indicating that mutations affecting this domain have biological relevance in
      terms of colorectal cancer disease course. These results suggest that knowledge
      of a patient's TP53 status, with respect to both the presence and the
      localization of the mutation, may be important in prognosis evaluation,
      particularly when selecting patients for more aggressive postoperative
      therapeutic intervention.

PMID- 9516973
TI  - Genetic abnormalities in parathyroid nodules of uremic patients.
AB  - The molecular pathway of autonomous growth of the parathyroid glands in uremic
      patients is poorly understood. We have analyzed 71 parathyroid lesions from 24
      patients with refractory hyperparathyroidism for allelic loss at chromosomes 1,
      3, 6, 9, 11, 12, 13, 15, and 17 and at the X chromosome. Microsatellite analysis
      was performed using 24 highly polymorphic markers. Deletions at chromosomes 1, 3,
      6, 11, 12, and 13 and at the X chromosome were detected in only 10 of 67 nodules
      (15%). No allelic loss of the p16 and p53 tumor suppressor genes or the
      extracellular calcium receptor gene was found. The X-chromosome inactivation
      assay revealed a monoclonal pattern in 58% of hyperplastic nodules in females.
      Our results indicate monoclonal growth in the majority of hyperplastic nodules
      and suggest that some of these lesions might be considered precursors for adenoma
      development.

PMID- 9516974
TI  - Gene amplification as a prognostic factor in primary brain tumors.
AB  - The most reliable prognostic factors for patients with primary malignant brain
      tumors remain histology, age, and functional status. Management of these
      individuals might be improved by quantifying pertinent molecular markers. We have
      measured the gene dosage of the epidermal growth factor receptor (EGFR), mouse
      double minute 2 (MDM2), and cyclin-dependent kinase 4 (CDK4) genes in a series of
      brain tumor specimens and correlated their amplification status with standard
      prognostic factors and survival. Individual tumor DNA was successively hybridized
      with probes for EGFR, MDM2, and CDK4. The signal was quantified by densitometry,
      and amplification was defined as gene signal > or = 2 times normal. Survival,
      age, Karnofsky performance status, and histology were correlated with gene
      amplification. Nineteen astrocytomas, 20 anaplastic astrocytomas, and 70
      glioblastomas had complete data available. Median survival with and without any
      form of gene amplification was 70.7 and 88.6 weeks, respectively (P = 0.0369).
      For the EGFR gene alone, those with and without amplification had a median
      survival of 58.9 and 88.6 weeks, respectively (P = 0.0104). By Cox analysis, only
      tumor histology (P = 0.04) and Karnofsky performance status (P = 0.0157) were
      significant independent predictors of survival. Gene amplification by itself was
      not predictive of survival, even for glioblastomas (P = 0.8249). The lack of
      correlation between gene amplification and survival for patients with primary
      malignant brain tumors may be because EGFR, MDM2, and CDK4 are only portions of
      larger signaling systems. Therefore, the lack of a direct correlation between a
      single gene and outcome is not entirely unexpected.

PMID- 9516975
TI  - RET/NTRK1 rearrangements in thyroid gland tumors of the papillary carcinoma
      family: correlation with clinicopathological features.
AB  - The papillary carcinoma family (PCF) of thyroid tumors includes a wide variety of
      neoplastic entities regarded as well-differentiated, poorly differentiated, and
      undifferentiated papillary thyroid carcinomas. Recent studies have established
      the presence of alternative oncogenic rearrangements of the RET and NTRK1 genes
      in a consistent fraction (< or = 50%) of papillary thyroid tumors. RET oncogenic
      rearrangements are also very frequent (approximately 60%) in Chernobyl radiation
      associated papillary thyroid neoplasias, which show an increased aggressiveness
      in terms of pathological stage at disease onset. These observations prompted us
      to study the relationship between the presence or absence of RET and NTRK1
      oncogenes and the clinicopathological features (age, sex, histopathology, and
      pTNMC2 staging) of 76 consecutive, non-radiation-related tumors of the PCF. As
      previously reported, statistical univariate analysis revealed a correlation
      between the combination of RET and NTRK1 (RET/NTRK1) positivity and young age of
      patients at diagnosis. In addition, a significant association was found between
      RET/NTRK1 positivity and locally advanced stage of disease at presentation (pT4:
      P < 0.015). The multivariate analysis confirmed that RET/NTRK1 activation
      parallels an unfavorable disease presentation, which may correlate with a less
      favorable disease outcome. Furthermore, within the PCF, the frequency of
      RET/NTRK1 positivity was not influenced by the different neoplastic subtypes or
      the tumor versus degree of differentiation.

PMID- 9516976
TI  - Telomerase enzyme activity and RNA expression during the multistage pathogenesis
      of breast carcinoma.
AB  - Telomerase, an RNA-containing enzyme, is associated with cellular immortality and
      malignancy. We investigated the role of telomerase during the multistage
      pathogenesis of breast cancer. We used the semiquantitative, PCR-based telomeric
      repeat amplification protocol assay for enzyme activity (42 specimens from 42
      patients) and a radioactive in situ assay for expression of its RNA component
      (human telomerase RNA; hTR) for the identification of telomerase-positive cells
      in archival resection samples (n = 67 from 39 patients). Low telomerase activity
      was detected in 1 (14%) of 7 samples of benign breast disease, in 4 (67%) of 6
      fibroadenomas, in 11 (92%) of 12 carcinoma in situ (CIS) lesions, and in 16 (94%)
      of 17 invasive breast cancers. There was a progressive increase in the mean
      telomerase levels with progressive increase in severity of histopathological
      change (P < 0.05). Almost all of 67 resection samples expressed hTR, irrespective
      of histology. Expression was low to moderate in some samples of normal epithelium
      and nonproliferative fibrocystic changes. hTR expression was limited to
      epithelial cells; expression in stromal cells, including those in fibroadenomas,
      was negative. Increased hTR expression was observed in some foci of apocrine
      metaplasia and atypical hyperplasia. Increased hTR expression was also observed
      in all CIS and invasive lesions, although considerable heterogeneity was noted.
      Focal up-regulation was frequently noted in CIS lesions in the vicinity of
      invasive tumors. Thus, up-regulation of hTR may be a predictive marker for
      invasive tumor development.

PMID- 9516977
TI  - Clinical features of ovarian cancer in Japanese women with germ-line mutations of
      BRCA1.
AB  - We analyzed the clinical features of 25 ovarian cancer patients who were
      associated with germ-line mutations of BRCA1 from four site-specific ovarian
      cancer families and seven breast-ovarian cancer families in Japan. The average
      age at diagnosis was 51.1 years (range, 38-77 years). Histological examination
      revealed 24 serous cyst adenocarcinomas in 25 patients. In 23 patients with clear
      clinical records, 3 patients had stage I disease, 17 had stage III disease, and 3
      had stage IV disease. Thirteen patients with stage III disease who were treated
      with cisplatin-containing chemotherapy following tumor reduction surgery showed
      more favorable outcomes in both the survival rate and disease-free intervals,
      compared with age- and treatment course-matched controls (5-year survival rate,
      0.786 versus 0.303; median disease-free interval, 91.43 versus 40.92 months; P <
      0.05 for both, by logarithmic rank test). Our statistical model for the
      inheritance of susceptibility to ovarian cancer was derived from the analysis of
      26 patients and 19 healthy carriers of 12 families. The expected lifetime risk of
      ovarian cancer is about 80% for women with mutations of BRCA1. These results
      suggest that the clinical outcome of ovarian cancer with germ-line mutations of
      BRCA1 appears to be more favorable than that with sporadic cases and that the
      disease penetrance among pedigrees with germ-line mutations of the BRCA1 gene is
      substantially high.

PMID- 9516978
TI  - Evaluation of epidermal growth factor-related growth factors and receptors and of
      neoangiogenesis in completely resected stage I-IIIA non-small-cell lung cancer:
      amphiregulin and microvessel count are independent prognostic indicators of
      survival.
AB  - We have determined the expression of transforming growth factor alpha (TGF
      alpha), amphiregulin (AR), CRIPTO, the epidermal growth factor receptor (EGFR),
      erbB-2, erbB-3, and tumor angiogenesis in a series of 195 patients with stage I
      IIIA non-small cell lung cancer (NSCLC) treated with radical surgery to define
      their usefulness as prognostic indicators of survival. A variable degree of
      specific staining in cancer cells was observed for the three growth factors and
      for the three growth factor receptors in the majority of NSCLC patients. A
      statistically significant association between overexpression of TGF alpha, AR,
      and CRIPTO was observed. Enhanced expression of AR was significantly correlated
      with enhanced expression of erbB-2 and advanced T-stage. A direct association was
      also detected for overexpression of TGF alpha and of erbB-2 or erbB-3,
      respectively. Sex, tumor size, nodal status, stage, microvessel count, as a
      measure of neovascularization, and AR overexpression significantly correlated
      with overall survival at univariate analysis. In a Cox multivariate analysis, the
      only characteristics with an independent prognostic effect on OAS were
      microvessel count [relative hazard (RH), 6.61; P < 0.00001), nodal status (RH,
      1.59; P = 0.0013), and AR overexpression (RH, 1.72; P = 0.02). These results
      suggest that evaluation of neoangiogenesis and of certain growth factors, such as
      AR, can be useful in addition to conventional pathological staging to select high
      risk NSCLC patients who may benefit from post-surgical systemic therapies.

PMID- 9516979
TI  - Bypass of abnormal MDM2 inhibition of p53-dependent growth suppression.
AB  - Oncoprotein MDM2 inhibits p53-dependent cell cycle arrest and apoptosis. MDM2
      overexpressing human cancer cell lines (n = 3) were found to be resistant to
      growth inhibition after infection by p53-expressing adenovirus (Ad-p53), as
      compared to low MDM2-expressing tumors (n = 3), in vitro. The growth of MDM2
      overexpressing tumors, however, was inhibited by p21-expressing adenovirus (Ad
      p21) infection, and the cyclin-dependent kinase-inhibitory region of p21 was
      sufficient to bypass the MDM2-p53 feedback loop. The phosphorylation state of Rb
      correlated with the response to either p53 or p21 gene therapy. MDM2
      overexpressing cancer cells infected by Ad-p21 also developed a quiescent large
      cell morphology. The results suggest that MDM2-mediated resistance to p53 may be
      bypassed by p21 and that the Rb phosphorylation state may predict the effects on
      growth after Ad-p53 or Ad-p21 infection.

PMID- 9516980
TI  - Correspondence Re: C. Caserini et al., Apoptosis as a determinant of tumor
      sensitivity to topotecan in human ovarian tumors: preclinical in vitro/in vivo
      studies. Clin. Cancer Res., 3: 955-961, 1997.

PMID- 9516981
TI  - Iron toxicity in yeast.
AB  - It has been found that yeast cells are sensitive to iron overload only when grown
      on glucose as a carbon source. Effective concentration of ferrous iron is much
      higher than that found in natural environments. Effects of ferrous iron are
      strictly oxygen dependent, what suggest that the formation of hydroxyl radicals
      in the Fenton reaction is a cause of the toxicity. Respiratory deficiency and
      pretreatment of cells with antimycin A prevent toxic effects in the late
      exponential phase of growth, whereas uncouplers and 2mM magnesium salts
      completely protect even the most vulnerable exponential cells. Generally, toxic
      effects correlate with the ability of cells to take up this metal. The results
      presented suggest that during ferrous iron overload iron is transported through
      the unspecific divalent cation uptake system which is known in fungi. The data
      suggest that recently described high and low affinity systems of iron uptake in
      yeast are the only source of iron in natural environments.

PMID- 9516982
TI  - The influence of iron occurring in the growth medium of Staphylococcus aureus on
      the bacterial adhesion to collagen.
AB  - The aim of this study was to investigate the influence of iron present in the
      growth medium of Staphylococcus aureus on the bacterial adhesion to collagen. The
      experiments were extended to determinate the siderophore production and to
      examine the S. aureus isolates surface hydrophobicity. The addition of iron to
      metal deficient defined medium causes the change in hydrophobicity of the
      examined S. aureus strains surfaces from hydrophilic to hydrophobic. The presence
      of iron in staphylococcal growth medium alters also the adhesion to the surface
      covered with collagen. Four out of six S. aureus strains adhere to collagen
      weaker when cells come from iron-rich medium. Majority of tested strains produce
      markedly less of siderophores in media containing the excess of iron (1 and 10
      microM Fe) and there is no staphylococcal siderophore activity in the growth
      medium with a very high concentration of this compound (120 microM Fe). The
      obtained results indicate that the iron-stressed conditions influence the
      staphylococcal adhesion to collagen.

PMID- 9516983
TI  - beta-Amylase production by some Bacillus cereus, Bacillus megaterium and Bacillus
      polymyxa [correction of polymaxa] strains.
AB  - The production of extracellular beta-amylase by some Bacillus cereus, Bacillus
      megaterium and Bacillus polymyxa [corrected] strains was investigated, and the
      maximal yields of the enzyme were 3.6; 9.3 and 20.4 U/mL of the culture fluid,
      respectively (U, 1 mumol of maltose equivalent per min at 30 degrees C). Several
      cultivation media were used for beta-amylase production. Bacillus cereus and some
      strains of Bacillus megaterium gave good yields of beta-amylase only in medium
      with the addition of nutrient broth. However, beta-amylase produced during growth
      in protein rich medium (nutrient broth) was highly unstable, probably due to
      inactivation by proteolytic enzymes co-existing in the culture fluid. Bacillus
      polymyxa [corrected] strains can produce good yields of beta-amylase on a semi
      synthetic medium consisting of inorganic salts, potato starch and inexpensive
      soybean extract instead of costly peptone and meat extract. The most potential
      beta-amylase producer was the strain Bacillus polymyxa [corrected] NCIB 8524. The
      tested Bacillus megaterium and Bacillus polymyxa [corrected] strains were
      apparently differentiated by temperature cultivation (30 and 37 degrees C)
      suitable for beta-amylase amylase yield.

PMID- 9516984
TI  - Haemolytic activity of Mycobacterium spp.
AB  - Haemolytic activity of clinical isolates of Mycobacterium bacilli (98) was
      determined by the method of King et al., 1993. During 3-h incubation, all M.
      tuberculosis (MTB) isolates (28) and one out of 38 M. avium-intracellulare (MAI)
      strains, produced a strong contact-dependent haemolysin (CDH). Six MAI strains
      expressed a weak CDH. One MAI isolate produced a strong and five other MAI
      strains a weak contact-independent haemolysin (CIH). Two M. bovis BCG strains and
      7 M. vaccae strains did not demonstrate haemolytic activity. The persistence of
      chosen Mycobacterium strains differing by haemolytic activity, in the spleens of
      infected C57BL/6 mice was examined. Mycobacteria producing a strong CDH (MTB
      H37Rv, MTB 101/92, MAI 83/93) or CIH (MAI 475/93) survived in the spleens of
      nonimmunized or M. bovis BCG-immunized mice for longer time than MAI strains
      expressing weak haemolytic activity or M. bovis BCG vaccine strain.

PMID- 9516985
TI  - Construction of mobilizable cloning vectors derived from pBGS18 and their
      application for analysis of replicator region of a pTAV202 mini-derivative of
      Paracoccus versutus pTAV1 plasmid.
AB  - Two mobilizable cloning vectors, designated pABW1 and pAWB2, were constructed
      basing on the E. coli vector pBGS18 and oriT originating from RK2. In pABW2 the
      kanamycin resistance gene was replaced by a novel tetracycline resistance
      cassette derived from Tn1721. Both vectors, specific for E. coli, allow to
      perform the cloning steps in E. coli and then to efficiently transfer the
      constructs by conjugation to the host of choice. A vector which cannot propagate
      in the given host can be applied for identification of the host specific plasmid
      replicator regions. With the use of pABW2 we defined the minimal replicator
      region of pTAV202-a mini-derivative of the large pTAV1 plasmid of P. versutus. We
      also proved that RepC' encoded on this fragment is the principal initiator
      replication protein and that oriV is located along its coding sequence.

PMID- 9516986
TI  - Escherichia coli defects caused by DnaK and DnaJ proteins overproduction.
AB  - Escherichia coli defects caused by the overproduction of DnaK and DnaJ proteins
      are presented. Induced overproduction of DnaK and DnaJ was determined by SDS-PAGE
      electrophoresis and immunoblots analysis. Elevated levels of both proteins are
      not deleterious for such cellular functions as growth, survival and cell
      morphology. However, instability of pJW14 plasmid (derivative of pACYC184) was
      observed as the result of dnaKdnaJ operon overexpression.

PMID- 9516987
TI  - The resistance to betalactam antibiotics of lactose-positive and lactose-negative
      strains of Escherichia coli.
AB  - Two groups of Escherichia coli (lactose-positive and lactose-negative strains)
      were assayed to evaluate the resistance to betalactam antibiotics using disk
      diffusion technique. 57.66% lactose-positive and 80.82% lactose-negative strains
      showed the resistance to ampicillin. In lactose-positive E. coli strains 5.00%
      and in lactose-negative 18.64% strains respectively were resistant to
      amoxicillin/clavulanic acid.

PMID- 9516988
TI  - Application of polymerase chain reaction for the detection of herpes simplex
      virus DNA.
AB  - Cerebrospinal fluids from 11 patients with encephalitis were studied for the
      presence of HSV specific DNA sequences. Also, the applicability of the PCR
      technique for HSV DNA detection in brain tissue of experimental animals infected
      with HSV-1 was tested. Our results indicated that PCR is effective, rapid and
      sensitive method to detect of HSV DNA in a variety of specimens. Obtained
      sensitivity was 4 copies of infectious HSV genome.

PMID- 9516989
TI  - Campylobacter jejuni in coccoid form does not reverse into spiral form in chicken
      guts.
AB  - The incubation of Campylobacter jejuni suspension in aerobic conditions results
      in the conversion of spiral cells into coccoid form. The present paper shows that
      such forms introduced into the alimentary tract of two-day-old chicks are not
      able to convert back into cultivable, infectious spiral forms, as has been
      suggested by some authors. Technical problems connected with this type of
      experiment are also discussed.

PMID- 9516990
TI  - Anoplocephalid cestodes of veterinary and medical significance: a review.
AB  - Cestodes of the family Anoplocephalidae Cholodkovsky, 1902, in their adult form,
      parasitize a variety of hosts, including reptiles, birds and mammals. To complete
      their life cycle, an intermediate host is required. This study gives a critical
      review of the life cycles of genera principally important to veterinary medicine
      (but sporadically infecting man): Anoplocephalinae (Anoplocephala,
      Anoplocephaloides, Bertiella and Moniezia) and Thysanosomatinae (Avitellina,
      Stilesia, Thysaniezia and Thysanosoma), using data reported by others and our own
      observations. The accepted paradigm on the biology of the anoplocephalid cestodes
      is that oribatid mites (Acarina) serve as intermediate hosts. However, as regards
      the genera Avitellina, Thysaniezia and Thysanosoma, it is still unclear whether
      oribatid mites are indeed the intermediate hosts, as larval forms (cysticercoids)
      have also been found in collembolans and psocids. Using the controversial
      biological cycle of Thysanosoma actinioides (Diesing, 1834), a theoretical
      methodological research proposal for parasitology was constructed which attempts
      to define a conceptional mark enabling us to predict and explain the parasite
      hosts' related phenomenon. Aspects of this proposal are discussed using the
      biology of the cestodes of family Anoplocephalidae, as examples.

PMID- 9516991
TI  - Lectins and tick-pathogen interactions: a minireview.
AB  - Lectins and their glycosylated receptors in a system of the tick-transmitted
      pathogen are the addressed topics which the minireview is dealing with. They
      participate in the reciprocal protein-saccharide interactions in the transmission
      of the causative agents of the tick-borne encephalitis and Lyme borreliosis by
      the ticks. Functional significance of the tick tissue specific lectins as well
      the lectins/aggulutinis of the transmitted pathogens in molecular ecology of the
      tick borne diseases has been shown.

PMID- 9516992
TI  - Vexillifera expectata sp. n. and other non-encysting amoebae isolated from organs
      of freshwater fish.
AB  - Four strains of non-encysting amoebae were isolated from organs of freshwater
      fishes and characterized using light and electron microscope. Morphology of three
      clonal strains was consistent with amoebae which had already been described from
      water habitats. Two strains, one isolated from kidney tissue of common goldfish,
      Carassius auratus (Linnaeus, 1758), and the second one from brain of chub,
      Leuciscus cephalus Linnaeus, 1758, were identified with Vannella platypodia
      (Glaser, 1912) Page, 1976. Both strains were identical, except for the length of
      glycostyles. The strain isolated from the liver of perch, Perca fluviatilis
      (Linnaeus, 1758), was assigned to the genus Vexillifera Schaeffer, 1926 as
      Vexillifera expectata sp. n. The taxonomic position of the fourth non-encysting
      strain could not be safely established, although it shares some trophic cell
      structures with protostelids (Protostelia, Eumycetozoea). We present its detailed
      description here also to demonstrate that amoeba stages of this type of organisms
      are capable to infect fishes.

PMID- 9516993
TI  - Scolex morphology of Proteocephalus tapeworms (Cestoda: Proteocephalidae),
      parasites of freshwater fish in the Palaearctic Region.
AB  - The morphology of the scoleces of 11 Proteocephalus species, parasites of
      freshwater fish in the Palaearctic Region, was compared using light and scanning
      electron microscopy. The following taxa were evaluated: Proteocephalus ambiguus
      (Dujardin, 1845); P. cernuae (Gmelin, 1790); P. exiguus La Rue, 1911; P.
      filicollis (Rudolphi, 1802); P. macrocephalus (Creplin, 1825); P. osculatus
      (Goeze, 1782); P. percae (Muller, 1780); P. pollanicola Gresson, 1952; P.
      sagittus (Grimm, 1872); P. thymalli (Annenkova-Chlopina, 1923); and P. torulosus
      (Batsch, 1786). Some features as overall shape of the scolex, its size, shape and
      size of an apical sucker were found to be fairly stable and species-specific. The
      taxa more easily distinguishable from congeners on the basis of their scolex
      morphology were P. cernuae, P. macrocephalus, P. osculatus, P. percae and P.
      torulosus. The taxonomic importance of the scolex is discussed.

PMID- 9516994
TI  - Redescription of the type-species of the cestode genus Deltokeras
      (Cyclophyllidea: Paruterinoidea).
AB  - The syntypes of Deltokeras ornitheios Meggitt, 1927 (the type-species of
      Deltokeras Meggitt, 1927), a parasite of Urocissa erythrorhyncha (Passeriformes,
      Corvidae) in South Asia, are redescribed. Deltokeras is considered a monotypic
      genus. An amended generic diagnosis is presented.

PMID- 9516995
TI  - Histopathological reactions of the blue shark, Prionace glauca, to postlarvae of
      Hepatoxylon trichiuri (Cestoda: Trypanorhyncha: Hepatoxylidae) in relationship to
      scolex morphology.
AB  - Postlarvae of the cestode Hepatoxylon trichiuri (Holten, 1802) were found
      attached to the surface of viscera of Prionace glauca (Linnaeus, 1758) taken from
      Atlantic coastal waters off the south coast of Massachusetts, USA. Gross anatomy
      of the attachment site shows a quadripartite rim surrounding a deep pit with
      holes corresponding to the penetration site of each tentacle. Hyperplasia of the
      liver capsule into outgrowths at the attachment site conform to the attachment of
      the bothridia. The cuboidal epithelium of the liver capsule became columnar
      forming papillary outgrowths, with a dense fibrotic reaction beneath the
      attachment site and infiltration by leukocytes and pigment containing
      granulocytic cells. Blood sinusoids beneath the attachment site are greatly
      enlarged. Postlarvae attached to the surface of the epigonal organs of three blue
      sharks were not accompanied by reactions. SEM examination of the scolex of H.
      trichiuri postlarvae revealed fused pairs of bothridia within infolded muscular
      lateral rims, porose tegument devoid of microtriches and a bilateral plane of
      symmetry in the tentacular armature.

PMID- 9516996
TI  - Lucionema balatonense gen. et sp. n., a new nematode of a new family
      Lucionematidae fam. n. (Dracunculoidea) from the swimbladder of the European
      pikeperch, Stizostedion lucioperca (Pisces).
AB  - A new nematode genus and species, Lucionema balatonense gen. et sp. n., is
      described from the swimbladder of the European pikeperch, Stizostedion lucioperca
      (L.), from Lake Balaton in Hungary; a new dracunculoid family Lucionematidae fam.
      n. is established to accommodate it. The hitherto monotypic family Lucionematidae
      shows affinities with the families Skrjabillanidae and Daniconematidae, differing
      from them mainly in having simple oesophagus without external oesophageal glands
      and the vulva situated near the middle of body; from the first family also in the
      absence of the buccal capsule and the bursa-like caudal alae in the male. The
      genus Lucionema gen. n. is characterized mainly by the presence of 8 cephalic
      papillae in two circlets, absence of spicules, presence of the copulatory plate,
      only 2 pairs of postanal papillae in the male, and by the distal part of the
      monodelphic uterus forming a posteriorly directed coil. The body length of L.
      balatonense females is 1074-1782 microns, that of the only available male 770
      microns. A key to the families of the Dracunculoidea is presented.

PMID- 9516997
TI  - Investigation of haematophagous arthropods for borreliae--summarized data, 1988
      1996.
AB  - Blood-sucking arthropods, collected in South Moravia, Czech Republic, were
      examined by darkfield microscopy for borreliae from 1988 to 1996. Among host
      seeking ixodid ticks (8481 Ixodes ricinus (L.), 372 Dermacentor reticulatus
      (Fabr.), 167 Haemaphysalis concinna Koch), borreliae were only observed in adult
      (23.2%), nymphal (17.2%) and larval (6.3%) I. ricinus. The prevalence of
      borreliae in I. ricinus did not vary considerably among habitats except for lower
      values in agroecosystems, xerothermic oak woods and grasslands. The frequency of
      intensity of spirochaetal infection (log10 counts of borreliae per tick) in I.
      ricinus approximated the negative binomial distribution. The proportions of host
      seeking female and nymphal ticks containing > 100 borreliae were 5.0% and 1.7%,
      respectively. Among preimaginal ticks (749 I. ricinus, 222 D. reticulatus, 82 H.
      concinna) parasitizing free-living forest birds and small mammals, borreliae were
      detected in 6.1% of larval and 10.3% of nymphal I. ricinus, and in one larval H.
      concinna; 3.2% of the birds and 19.4% of the mammals carried infected ticks.
      Among 3464 female mosquitoes (Culicidae) of 6 species, 4.1% contained
      spirochaetes: 1.4% of Aedes vexans Meig., 1.3% of A. cantans (Meig.), 2.2% of A.
      sticticus (Meig.), 2.2% of Culex pipiens pipiens L. and 5.9% of C. p. molestus
      Forskal. Borreliae were also detected in 8.4% of 142 fleas (Siphonaptera, largely
      Ctenophthalmus agyrtes Heller and Hystrichopsylla talpae Curtis) collected from
      small mammals. Twelve isolates of B. burgdorferi sensu lato have been identified
      to genospecies: 6 strains from I. ricinus (4 Borrelia garinii Baranton et al., 1
      B. afzelii Canica et al. and 1 B. lusitaniae Le Fleche et al.), 1 strain from A.
      vexans (B. afzelii), 2 strains from C. agyrtes (B. afzelii), and 3 strains from
      host rodents (B. afzelii).

PMID- 9516998
TI  - Borrelia garinii in Ixodes ricinus ticks from southern Poland.

PMID- 9517000
TI  - Characterization of storage proteins in Daucus carota L.: two novel proteins
      display zygotic embryo specificity.
AB  - Although maturation-related proteins are well known in the endosperm of
      albuminous seeds, an important question is whether the zygotic embryo possesses
      its own maturation proteins. We report on the isolation and partial
      characterization of storage proteins of carrot (Daucus carota L. var Nandor) dry
      achenes and isolated zygotic embryos, using one- and two-dimensional
      electrophoresis techniques, HPLC and amino acid sequencing. The presence of a
      series of abundant polypeptides showing charge heterogeneity, that are rapidly
      degraded upon germination, was revealed in the endosperm. These proteins
      consisted of glycoproteins, the most abundant of which displayed a molecular mass
      (M(r)) of 58,000, albumins of M(r) 42,000 comprising at least one beta-1,3
      glucanase, and two globulins of M(r) 90,000 and 50,000-55,000 respectively, the
      second being an oligomer composed of three subunits of M(r) 13,000, 20,000 and
      30,000. None of these storage proteins identified in the endosperm were detected
      in zygotic embryos. In contrast, two novel proteins were isolated from zygotic
      embryos, namely a globulin family of M(r) 50,000 and pI 6.3-6.8, which was named
      "daucin", and a late embryogenesis abundant (LEA) protein family of M(r) 25,000
      and pI 6.3-6.6, named "RAB25". Since the latter proteins are apparently absent of
      the endosperm, these results suggest that the maturation of carrot zygotic
      embryos requires its own specific set of storage and LEA proteins.

PMID- 9516999
TI  - Molecular characterization and physiological role of a glyoxysome-bound ascorbate
      peroxidase from spinach.
AB  - cDNAs encoding two cytosolic and two chloroplastic ascorbate peroxidase (AsAP)
      isozymes from spinach have been cloned recently [Ishikawa et al. (1995) FEBS
      Lett. 367: 28, (1996) FEBS Lett. 384: 289]. We herein report the cloning of the
      fifth cDNA of an AsAP isozyme which localizes in spinach glyoxysomes (gAsAP). The
      open reading frame of the 858-base pair cDNA encoded 286 amino acid residues with
      a calculated molecular mass of 31,507 Da. By determination of the latency of AsAP
      activity in intact glyoxysomes, the enzyme, as well as monodehydroascorbate
      (MDAsA) reductase, was found to be located on the external side of the
      organelles. The cDNA was overexpressed in Escherichia coli (E. coli). The
      enzymatic properties of the partially purified recombinant gAsAP were consistent
      with those of the native enzyme from intact glyoxysomes. The recombinant enzyme
      utilized ascorbate (AsA) as its most effective natural electron donor;
      glutathione (GSH) and NAD(P)H could not substitute for AsA. The substrate
      velocity curves with the recombinant enzyme showed Michaelis-Menten type kinetics
      with AsA and hydrogen peroxide (H2O2); the apparent Km values for AsA and H2O2
      were 1.89 +/- 0.05 mM and 74 +/- 4.0 microM, respectively. When the recombinant
      enzyme was diluted with AsA-depleted medium, the activity was stable over 180
      min. We discuss the H2O2-scavenging system maintained by AsAP and the
      regeneration system of AsA in spinach glyoxysome.

PMID- 9517001
TI  - Enhanced expression of an antimicrobial peptide sarcotoxin IA by GUS fusion in
      transgenic tobacco plants.
AB  - To enhance the disease resistance of plants expressing a foreign peptide, the
      gene for sarcotoxin IA, which is an antimicrobial peptide from an insect
      consisting of 39 amino acid residues, was introduced into tobacco (Nicotiana
      tabacum) under the control of a high expression promotor via Agrobacterium
      mediated transformation. In transgenic plants, sarcotoxin IA mRNA accumulated to
      detectable levels, however, the amount of the peptide produced was so small that
      we could scarcely detect it by protein gel blot analysis, probably because of the
      instability of short peptides in plant cells. To improve the expression
      efficiency, genes for four types of amino-terminal and carboxyl-terminal
      translational fusions of sarcotoxin IA together with the GUS gene were introduced
      into tobacco. In all four types of transgenic tobacco plants, high level
      transcripts similar to that in the direct expression sarcotoxin IA construct were
      found. Protein gel blot analysis with both anti-sarcotoxin IA and GUS antibodies
      showed production of high levels of fusion protein in all transgenic plants.
      Among them, three types had abnormal membranes and phenotypes, although no such
      abnormalities were found in transgenic plants in which only sarcotoxin IA was
      expressed in a secretable form. All together, these results indicated that, for
      stable and effective expression of a foreign short peptide in transgenic plants,
      expression as a fusion protein is useful and that secretion of sarcotoxin IA
      outside of cells is necessary for generation of useful antimicrobial transgenic
      plants.

PMID- 9517002
TI  - Isolation and characterization of a water stress-specific genomic gene, pwsi 18,
      from rice.
AB  - One of the water stress-specific cDNA clones of rice characterised previously,
      wsi18, was selected for further study. The wsi18 gene can be induced by water
      stress conditions such as mannitol, NaCl, and dryness, but not by ABA, cold, or
      heat. A genomic clone for wsi18, pwsi18, contained about 1.7 kbp of the 5'
      upstream sequence, two introns, and the full coding sequence. The 5'-upstream
      sequence of pwsi18 contained putative cis-acting elements, namely an ABA
      responsive element (ABRE), three G-boxes, three E-boxes, a MEF-2 sequence, four
      direct and two inverted repeats, and four sequences similar to DRE, which is
      involved in the dehydration response of Arabidopsis genes. The gusA reporter gene
      under the control of the pwsi18 promoter showed transient expression in response
      to water stress. Deletion of the downstream DRE-like sequence between the distal
      G-boxes-2 and -3 resulted in rather low GUS expression.

PMID- 9517003
TI  - Molecular cloning of plant spermidine synthases.
AB  - Four cDNAs for spermidine synthase (SPDS), which converts the diamine putrescine
      to the higher polyamine spermidine using decarboxylated S-adenosylmethionine as
      the co-factor, were isolated from Nicotiana sylvestris, Hyoscyamus niger, and
      Arabidopsis thaliana. When the N.sylvestris SPDS cDNA was expressed in a SPDS
      deficient E. coli mutant, the recombinant protein showed high SPDS activity, but
      did not have any spermine synthase activity. The plant SPDSs have molecular
      masses of about 34 kDa, possess the co-factor binding motifs which have been
      proposed for S-adenosylmethionine, and are more homologous in amino acid sequence
      to tobacco putrescine N-methyltransferase (PMT) than to SPDSs from mammals and E.
      coli. The SPDS gene is expressed in root, stem, and leaf in N.sylvestris, whereas
      the PMT gene is expressed only in root. The potential evolution of plant SPDS and
      PMT, and their evolutionary relationships with animal SPDS are discussed.

PMID- 9517005
TI  - Vacuolar membrane lesions induced by a freeze-thaw cycle in protoplasts isolated
      from deacclimated tubers of Jerusalem artichoke (Helianthus tuberosus L.).
AB  - The processes of freezing injury in Jerusalem artichoke (Helianthus tuberosus L.)
      tubers were studied using protoplasts isolated from cold-acclimated and
      deacclimated tubers. Prior to freezing, protoplasts were preloaded with 10 microM
      fluorescein diacetate (FDA) in an isotonic sorbitol solution. After freeze
      thawing at various temperatures, cell viability was evaluated under a
      fluorescence microscope. In cold-acclimated tubers, more than 80% of protoplasts
      survived freezing to -20 degrees C. By contrast, in deacclimated tubers, the cell
      survival abruptly declined after freezing to temperatures below -5 degrees C.
      Thus, freezing tolerance differed significantly between protoplasts isolated from
      cold-acclimated and deacclimated tubers. Two distinct types of cell injury, which
      were caused by either damage to plasma membrane (cell-lysis type) or by damage to
      the vacuolar membrane (abnormal-staining type), were observed, depending on the
      cold hardiness and freezing temperature. In the cells of the abnormal-staining
      type, shrinkage of the central vacuolar space and simultaneous acidification of
      the cytoplasmic space were characteristically observed immediately before
      complete cell-rehydration during thawing. The decrease in freezing tolerance of
      protoplasts after deacclimation was suggested to be due mainly to destabilization
      of the vacuolar membrane by freeze-induced dehydration stress.

PMID- 9517004
TI  - Dynamic organization of microtubules in guard cells of Vicia faba L. with diurnal
      cycle.
AB  - Stomatal movement is regulated by changes in the volume of guard cells, thought
      to be mainly controlled by an osmo-regulatory system. In the present study, we
      examined the additional involvement of cytoskeletal events in the regulation of
      stomatal movement. Microtubules (MTs) in guard cells of Vicia faba L., grown
      under sunlight, were observed during the day and night by immunofluorescence
      microscopy. Cortical MTs began to be organized in a radial array at dawn and
      increased in numbers in the morning following the increase in the stomatal
      aperture size. Thereafter, MTs became localized near the nucleus and began to be
      destroyed from the evening to midnight, following the decrease in stomatal
      aperture size. These diurnal changes in MT organization were observed even two
      days after transfer from natural light condition to total darkness, and were
      accompanied by corresponding changes in stomatal aperture. The increase in
      stomatal aperture size in the early morning was inhibited by 50 microM
      propyzamide, which destroys cortical MTs in guard cells, whereas the decrease in
      aperture size in the evening was suppressed by 10 microM taxol, which stabilizes
      cortical MTs. These results suggest that radially-organized cortical MTs of guard
      cells may control diurnal stomatal movement.

PMID- 9517006
TI  - Evidence for the cell wall involvement in temporal changes in freezing tolerance
      of Jerusalem artichoke (Helianthus tuberosus L.) tubers during cold acclimation.
AB  - We studied the mechanism of cold acclimation of Jerusalem artichoke (Helianthus
      tuberosus L.) tubers with special reference to the role of the cell wall. During
      the cold-acclimation process from September to January, the freezing tolerance of
      tubers increased from -2.8 degrees C to -8.4 degrees C (LT50). By contrast, the
      isolated protoplasts constitutively showed a consistent high level of freezing
      tolerance (LT50; below -25 degrees C) throughout the period. In tuber tissues,
      freezing injury was effectively protected by the external addition of isotonic
      solutions. Cryomicroscopic observations revealed that tissue cells mounted in
      isotonic solutions plasmolyzed upon freezing; tissue cells mounted in water
      collapsed with a tight attachment of plasma membrane to the cell wall. Upon
      freezing of intact tissues in water to temperatures below the critical range, the
      cytoplasm was irreversibly acidified as revealed by a fluorescence pH-ratiometry,
      suggesting that occurrence of detrimental cellular events leading to permanent
      cell injury. The freeze-induced acidification of cytoplasm was also effectively
      prevented by the external addition of isotonic solutions. These results suggest
      that the tight attachment of the plasma membrane to the cell wall during freezing
      may have a harmful effect on cells, in particular on the plasma membrane,
      possibly due to mechanical or some sort of chemical/ physico-chemical interaction
      with the cell wall.

PMID- 9517008
TI  - The influences of two plant nuclear matrix attachment regions (MARs) on gene
      expression in transgenic plants.
AB  - Nuclear matrix attachment regions (MARs) are thought to influence gene expression
      by anchoring active chromatin to the proteinaceous nuclear matrix. In this study,
      two plant DNA fragments with strong MAR activity were selected and tested for
      their effects on expression of a linked reporter gene in transgenic tobacco. One
      MAR was isolated from the 5' flanking region of a pea vicilin gene previously
      reported to be expressed in a copy number-dependent manner in transgenic tobacco.
      A second MAR was isolated from the genome of Arabidopsis thaliana by preselection
      for autonomously replicating sequence (ARS) activity in yeast. Flanking copies of
      the A. thaliana MAR stimulated median reporter gene expression in transgenic
      plants by five to ten fold. Neither MAR significantly reduced the variation in
      transgene expression between individual transformants, or conferred copy number
      dependence in gene expression.

PMID- 9517007
TI  - Purification of a novel type of SDS-dependent protease in maize using a
      monoclonal antibody.
AB  - A protease which was activated by SDS was purified to homogeneity from maize
      leaves. On the basis of its proteolytic activity towards ribulose-1,5
      bisphosphate carboxylase/ oxygenase (Rubisco) or a synthesized peptide, the
      purification was carried out using immunoaffinity chromatography with a
      monoclonal antibody raised against a partially purified enzyme by native gradient
      PAGE. The purified protease showed three bands at 40, 15, and 13 kDa on SDS-PAGE,
      indicating that it was composed of heterogeneous subunits. The protease was
      specifically activated by SDS (optimum = 0.4% for Rubisco proteolysis), but not
      by poly-L-lysine, fatty acids, or ATP. The protease had a pH optimum around 4.9.
      beta-Mercaptoethanol stimulated the activity only in the presence of SDS. The
      proteolytic activity was sensitive to E-64 and leupeptin but was resistant to
      EDTA, suggesting that the enzyme was an SH-protease. Thus, this enzyme is a novel
      type of SDS-dependent protease which differs from proteasome, matrix
      metalloproteinase, and other proteases reported in many organisms.

PMID- 9517009
TI  - An evaluation of structural descriptors and clustering methods for use in
      diversity selection.
AB  - An evaluation of the suitability of a number of structural descriptors and
      clustering methods for use in diversity selection is presented. The methods are
      compared by their success in simulated biological activity predictions. The
      results suggest that simple 2D structural descriptors are particularly effective
      and that hierarchical clustering methods are superior to the non-hierarchical
      methods traditionally used for diversity related tasks. Results are presented
      which suggest that the difference in the utility of the descriptors can be
      accounted for by the different extent to which each encodes information relevant
      to the forces of ligand-receptor binding.

PMID- 9517010
TI  - Computer-assisted design of new drugs based on retrometabolic concepts.
AB  - Retrometabolic drug design approaches incorporate metabolic and toxicological
      considerations into the drug design process and represent a novel, systematic
      methodology for the design of safe compounds. Two major design concepts aimed to
      increase the therapeutic index (the activity/toxicity ratio) of drugs were
      developed. Chemical delivery systems (CDS) are primarily used to allow targeting
      of the active biological molecules to specific target sites or organs based on
      predictable enzymatic activation. Soft drug approaches are used to design new
      drugs by building in the molecule, in addition to the activity, the most desired
      way in which the molecule is to be deactivated and detoxified subsequent to
      exerting its biological effects. Special computer programs were developed that
      starting from a lead compound generate complete libraries of possible soft
      analogs and then help ranking these candidates based on isosteric-isoelectronic
      comparisons, predicted solubility/partition properties, and estimated metabolic
      rates. The novel field of large peptide-CDSs imposes special challenges, but a
      new, remarkably simple model was developed to estimate partition properties for a
      wide range of compounds, including quite large peptide derivatives. A suggested
      change of about five order of magnitudes in the distribution coefficient can
      explain the "lock in" mechanism of brain-targeting delivery systems.

PMID- 9517011
TI  - Application of Kohonen Neural Networks in classification of biologically active
      compounds.
AB  - Automated data classification is an indispensable tool in Drug Design. It allows
      to select homogeneous training sets or to distinguish compounds with required
      biological properties. The Kohonen Neural Networks (KNN) suggest new means for
      classification of biologically interesting compounds. In this paper, first,
      capabilities of KNN in data dimensionality reduction are presented as compared
      with the capabilities of Principal Component Analysis (PCA) and Hierarchical
      Cluster Analysis (HCA). The advantages of KNN become evident with increasing data
      dimensionality and size of the training set. Then, new methods are suggested to
      evaluate the quality of KNN models. Finally, a case study on chemical and
      biological data is presented. The database studied includes more than 2000
      organophosphorous potent pesticides. The Kohonen maps were obtained which allow
      to distinguish compounds with different biological behavior.

PMID- 9517012
TI  - Nonlinear neural mapping analysis of the adverse effects of drugs.
AB  - Numerous drugs have been identified as presenting adverse effects towards the
      driving of vehicles. A large set of these drugs was compiled and classified into
      ten categories. Nonlinear neural mapping (N2M) was used to derive a typology of
      these molecules and also to link their adverse effects to therapeutic categories
      and structural information.

PMID- 9517013
TI  - Pharmacophores in drug design and discovery.
AB  - Compounds containing a specific pharmacophore--the minimum structural features
      necessary for enzyme binding--can be retrieved from a database such as the
      National Cancer Institute repository by means of three-dimensional (3D)
      searching, which allows the retrieval of all compounds possessing a specified set
      of atoms with a given 3D geometry. The ways in which pharmacophores can be found
      and characterized and the details of the 3D searching methods are described.
      Elaboration of compounds found in such searches and their subsequent development
      as lead drugs is also discussed.

PMID- 9517014
TI  - Enhancing the flexibility and adaptability of the DARC structural representation
      for computer-aided drug design.
AB  - Noticeable progress has been achieved in the determination of dynamic
      topochromatic variables for the structural representation of compounds and their
      situation in a given population. These independent structural variables can be
      further combined into more complex variables. Their contributions to the
      evolution of an associated property can therefore be evaluated with certainty.
      The risk of having correlated variables is avoided while the structural
      description remains exhaustive. In order to enhance the interpretative ability of
      the QSAR model, one or several physicochemical properties can be taken with these
      structural parameters as explanatory variables. Typically, partition
      coefficients, 3-D and quantum mechanical data are used for this purpose. The
      structural aspects not taken into account by the physicochemical parameters are
      reflected in the remaining topochromatic variables. The use of these new concepts
      is presented in a study of carbazole mutagenicity. The model explains 99% of the
      total variance with one external property and four additional topochromatic
      variables. The modulation of the heat of formation of an intermediate by two
      topochromatic variables suggests a much more precise interpretation than a simple
      combination of the usual external variables.

PMID- 9517015
TI  - Internal axis molecular parameters, torsional energies and matrix elements of
      methyl mercaptan-D1.
AB  - In this paper an internal axis method Hamiltonian model has been applied to
      evaluate the torsional-rotational molecular parameters of asymmetrically
      substituted methyl mercaptan (CH2DSH) using previously observed microwave
      transitions. The torsional barrier potential barrier functions V1, V2 and V3 have
      been refined. The observed microwave transition frequencies have also been fitted
      to an energy expansion model, which allowed accurate predictions of yet
      unobserved transition frequencies with microwave accuracy. These values are
      independent of the Hamiltonian model used and will prove valuable for
      astrophysical detection. The matrix elements between various torsional sub-levels
      upto the fourth excited torsional state in the ground vibrational state.

PMID- 9517016
TI  - Second order Coriolis resonance between the C-O stretch and the CH3 rock levels
      of methanol involving excited torsional state.
AB  - In this paper, it is shown that the interaction responsible for making the series
      of 'forbidden' transitions from the state (n tau K) = (110) in the ground
      vibrational (v = 0) state of the levels of (122+) in the CH3-rocking vibrational
      state (v = r) of methanol is 'Coriolis' resonance and not 'Fermi' resonance as
      proposed in a recent publication. This has been established from the J-dependence
      of the observed perturbed energy spacings between the two interacting pairs from
      high resolution spectroscopic analysis. The J-dependence clearly follows the
      classic 'Coriolis' interaction matrix elements for delta K = 2, which would not
      occur if the interaction were due to 'Fermi' resonance.

PMID- 9517017
TI  - beta-Lactam antibiotics. Spectroscopy and molecular orbital (MO) calculations.
      Part I: IR studies of complexation in penicillin-transition metal ion systems and
      semi-empirical PM3 calculations on simple model compounds.
AB  - IR studies were preformed to determine possible transition metal ion binding
      sites of penicillin, the observed changes in spectral position and shape of
      characteristic IR bands of cloxacillin in the presence of transition metal ions
      (both in solutions and in the solid state) indicate formation of M-L complexes
      with engagement of -COO- and/or -CONH- functional groups. The small shift of vC=O
      towards higher frequencies rules out direct M-L interaction via beta-lactam
      carbonyl. PM3 calculations on simple model compounds (substituted formamide,
      cyclic ketones, lactams and substituted monocyclic beta-lactams) have been
      performed. All structures were fully optimized and the calculated bond lengths,
      angles, heats of formation and C=O stretching frequencies were discussed to
      determine the beta-lactam binding sites and to explain its susceptibility towards
      nucleophilic attack (hydrolysis in vitro) and biological activity. The relative
      changes of calculated values were critically compared with available experimental
      data and same correlation between structural parameters and in vivo activity was
      shown.

PMID- 9517019
TI  - [Biomechanical evaluation laboratories for medical products].

PMID- 9517018
TI  - Fluorescence quenching of ethidium ion by porphyrin cations and quaternary
      ammonium surfactants in the presence of DNA.
AB  - Fluorescence quenching of free and DNA-bound ethidium bromide (EB) by a number of
      quaternary ammonium and other compounds was studied. For free EB or bound EB at
      lower DNA concentration the fluorescence quenching follows the Stern-Volmer
      equation and at higher DNA concentration follows an exponential model. At least
      at low quencher concentrations the quenching efficiency varies with DNA or NaCl
      concentrations and is about 100 times greater for bound than free EB. The
      quenching pathways may involve energy transfer and conformational loosening or
      distortion of the DNA helix in addition to possible electron transfer.

PMID- 9517020
TI  - [The European monitoring system for medical products (vigilance system)].

PMID- 9517022
TI  - [Optimal process control in dialysis therapy].

PMID- 9517021
TI  - [Quality control of shunt systems--status of automated testing of cerebrospinal
      fluid drainage systems].

PMID- 9517023
TI  - [Individual surgical planning as a method of quality management in
      oromaxillofacial surgery].

PMID- 9517024
TI  - [Quality assurance in medicine. Use of technical information methods and tools].

PMID- 9517025
TI  - [Computer-assisted calculation of sectional forces of the femur].

PMID- 9517026
TI  - [Analysis of implant component stability of new materials in axis adjusted knee
      joint prostheses using finite element analysis].

PMID- 9517027
TI  - [Biomechanics of the prosthetically managed femur--effect of prosthesis shaft
      coating].

PMID- 9517028
TI  - [Simulation of elasto-mechanical behavior of the human mandible using individual
      finite element modeling].

PMID- 9517029
TI  - [Complex adaptive estimation algorithms in biosignal processing].

PMID- 9517030
TI  - [TEMPLAS online spike detection with Windows NT in epilepsy monitoring].

PMID- 9517031
TI  - [Adaptive methods in description and comparison of the distribution of biological
      signals].

PMID- 9517032
TI  - [Development and realization of an EEG simulator].

PMID- 9517033
TI  - [Conformational radiotherapy].

PMID- 9517034
TI  - [Boron neutron capture therapy (BNCT)].

PMID- 9517036
TI  - [Readout of lutetium oxyorthosilicate crystals with avalanche photodiodes for
      high resolution positron emission tomography].

PMID- 9517035
TI  - [Measuring cerebral blood flow using electron beam computerized tomography].

PMID- 9517037
TI  - [Modifying magnetic susceptibility of ceramic implant materials].

PMID- 9517038
TI  - [Simultaneous imaging of the structure and function of clinically relevant hollow
      organs].

PMID- 9517039
TI  - [Atomic force study of solid body-induced blood coagulation in relation to
      electronic surface properties].

PMID- 9517040
TI  - [Methods for determining hardness of nanostructures by combination of atomic
      force microscopy and ultrasound excitation].

PMID- 9517041
TI  - [Mechanical fatigue behavior of glass and ceramics].

PMID- 9517042
TI  - [Nondestructive hard tissue histotomography by confocal laser scanning microscopy
      as a prerequisite for prospective in vitro test series exemplified by tooth
      enamel demileralization].

PMID- 9517043
TI  - [Changes in the properties of polyhydroxybutyric acid due to sterilization].

PMID- 9517044
TI  - [Complement activation and liberation of cytokines from monocytes as indicators
      of biocompatibility of polyhydroxybutyric acid].

PMID- 9517045
TI  - [R-spike detection for rhythm monitoring in real time with a fuzzy logic
      detector].

PMID- 9517047
TI  - [Fetal heart rate variability in pregnancy. Spectral analysis based on
      magnetocardiography].

PMID- 9517046
TI  - [Analysis of the complexity of fetal heart rate. Determining the dimension].

PMID- 9517048
TI  - [Variability of the heart rate and QRS conformation of cardiograms in healthy
      probands and arrhythmia patients].

PMID- 9517049
TI  - [A flexible ECG compression algorithm based on wavelet transformation for use in
      transmission systems].

PMID- 9517050
TI  - [Cardiac telemonitoring by joining near telemetry and internet transmission].

PMID- 9517051
TI  - [Optimizing electrode geometry and pulse configuration for stimulation of the
      atrium with floating electrode rings].

PMID- 9517053
TI  - [A new high temperature soldering method for manufacturing electrical pacemaker
      housing designs].

PMID- 9517052
TI  - [Controlled frequency-adapted stimulation of the heart based on mathematical
      identification of the cardiovascular system].

PMID- 9517054
TI  - [Are there sex-specific differences in pacemaker selection].

PMID- 9517055
TI  - [Measuring muscle force with nuclear magnetic resonance spectroscopy].

PMID- 9517056
TI  - [Simple bilateral gait analysis].

PMID- 9517057
TI  - [Training device for fixation of osteosynthesis screws].

PMID- 9517058
TI  - [Ultrasound measurements for evaluating pin fixation in external fixator
      devices].

PMID- 9517060
TI  - [Biomechanics of external fixation devices and optimal tactics for treating long
      bone fractures].

PMID- 9517059
TI  - [Estimating the elastic anisotropy of bone by V(z) measurements].

PMID- 9517061
TI  - [Objective assessment of equilibrium function in patients with polyneuropathies
      and cerebellar diseases].

PMID- 9517062
TI  - [Computer-assisted acoustic speech analysis in therapy follow-up of patients with
      cleft lip-jaw-palate].

PMID- 9517063
TI  - [Online monitoring of change points].

PMID- 9517064
TI  - [Use of modern time series analysis in detection and quantification of autonomic
      dysfunctions].

PMID- 9517065
TI  - [Improvement of site resolution and dynamics in ultrasound imaging by depth
      dependent mismatched filter pulse compression].

PMID- 9517066
TI  - [Methods for the analysis of intracranial pressure signals].

PMID- 9517067
TI  - [Current status of risk discussion of low frequency electric and magnetic fields
      and high frequency electromagnetic radiation].

PMID- 9517068
TI  - [Exposure facilities for study of the effect of high frequency electromagnetic
      fields on biological systems].

PMID- 9517069
TI  - [How risky is the relative risk in epidemiologic studies?].

PMID- 9517070
TI  - [Modification of technical medical equipment by cellular telephones].

PMID- 9517072
TI  - [Development of a bipolar clamp forceps for minimal invasive surgery].

PMID- 9517071
TI  - [Magnetic resonance tomography and thermal hot spots caused by high frequency
      electromagnetic fields].

PMID- 9517073
TI  - [Development of a suturing device for minimal invasive surgery].

PMID- 9517074
TI  - [Modeling the transport properties of Si,C-resistors for electronic implants
      based on microscopic material analysis].

PMID- 9517075
TI  - [Chemical surface polishing of laser constructed tantalum tubes for use as
      coronary stents].

PMID- 9517076
TI  - [Development of a replication technique for the preparation of smooth solid body
      surfaces as substrate material for AFM/STM microscopy].

PMID- 9517077
TI  - [Immobilized heparin as an incrustation-resistant layer on urologic implants].

PMID- 9517078
TI  - [Exposure of the bioresorbable polymer poly(beta-hydroxybutyric acid) to various
      laser systems].

PMID- 9517079
TI  - [Perception of electrical alternating currents by thermal effects].

PMID- 9517080
TI  - [3-D localization of electrodes in multichannel ECG recording using analysis of
      stereo color images].

PMID- 9517081
TI  - A simple computer model to simulate ECG based on ionic channels.
AB  - The presented computer model reconstructs the ECG with 500 myocardium cells based
      on seven ionic channels. The low hardware-requirement and the exact demonstration
      of physiological and pathophysiological coherence make this simulation model very
      useful for medical scientific education.

PMID- 9517082
TI  - [Methods of pattern recognition for detection of neurohumoral information in
      monophasic action potentials].

PMID- 9517083
TI  - [Analysis of ventricular evoked action potential for the detection of
      chronotropic status].

PMID- 9517084
TI  - [Modeling the inotropic effect on the intracardiac impedance signal as the basic
      principle of regulated frequency adjustment by the cardiac pacemaker].

PMID- 9517086
TI  - [Noninvasive measurement of brain movement].

PMID- 9517085
TI  - [Modeling myocardial Ca regulation mechanisms for the development of anti
      tachycardic stimulation methods].

PMID- 9517087
TI  - [Studies of by transthoracic defibrillation-induced electrical field distribution
      in detailed finite element models of the human body].

PMID- 9517088
TI  - [Generation and refinement of detailed finite element models of the human body].

PMID- 9517089
TI  - [Decimation of triangle meshes for describing limited surfaces in detailed finite
      element models of the human body].

PMID- 9517090
TI  - [Finite element method simulation of the effect of an administration of laser
      energy in the tooth root canal].

PMID- 9517091
TI  - [Analysis of load studies of the spine].

PMID- 9517092
TI  - [Methods for noninvasive measurement of the compliance of arteries].

PMID- 9517093
TI  - [Tissue diagnosis by autofluorescence].

PMID- 9517094
TI  - [Technical control realization of an implantable measuring system for impedance
      spectroscopy for diagnosis of rejection].

PMID- 9517095
TI  - [Diagnosis of rejection after kidney transplantation by impedance spectroscopy
      with an implantable measuring system].

PMID- 9517096
TI  - [Noninvasive monitoring of anti-arrhythmia sotalol therapy by analysis of
      intracardiac signals].

PMID- 9517097
TI  - [Effect of ischemia on signal morphology of monophasic action potentials and
      evoked stimulus responses].

PMID- 9517098
TI  - [Lasers in medical diagnosis and therapy].

PMID- 9517100
TI  - [Confocal laser scanning microscopy (CLSM) of cortical bone--comparative imaging
      with conventional microscopy].

PMID- 9517099
TI  - [Optical dual canal measuring system for the detection of disorders of
      mitochondrial metabolism in situ].

PMID- 9517101
TI  - [Light application to photosensitized tissues. Dosimetry and laser safety in
      photodynamic therapy].

PMID- 9517102
TI  - [Laser-assisted, intraoperative diagnosis of tumor fluorescence with disulfonated
      aluminum-phthalocyanine as an aid in the microsurgical removal of brain tumors.
      Animal experiment studies].

PMID- 9517103
TI  - [Realization of a cost-effective system for simultaneous registration of EEG/MEG
      and video signals].

PMID- 9517104
TI  - [Effect of discrete analysis of boundary elements on forward calculation and the
      inverse problem in EEG and MEG].

PMID- 9517105
TI  - [Reproducing system-related MEG coordinates on a 3D reconstructed MRI data
      display].

PMID- 9517106
TI  - Benign rolandic epilepsy investigated by magnetoencephalography.

PMID- 9517107
TI  - Combined study of ischemic brain conditions using magnetencephalography and
      proton magnetic resonance spectroscopy imaging.

PMID- 9517108
TI  - [Weighted averaging of weak neuronal magnetic fields with reference to covariance
      of strong noise components].

PMID- 9517109
TI  - [Detection of DC related biomagnetic fields in muscle injury currents in vivo].

PMID- 9517110
TI  - [Modeling of impulse transmission in the heart exemplified by the Visible Man
      dataset].

PMID- 9517111
TI  - [Determining the impulse transmission phenomenon in locally limited ventricular
      tissue based on modeling and measuring transmitted action potentials].

PMID- 9517112
TI  - [Calculating stationary electrical fields in detailed models of the human heart
      using finite element analysis].

PMID- 9517113
TI  - [Blood flow studies with stents].

PMID- 9517114
TI  - [Experimental evaluation of lumen patency control by balloon expandable coronary
      stents].

PMID- 9517115
TI  - [Quantifying the recoil of coronary stents: an in vitro study with the coronary
      stenosis model using high resolution roentgen technique].

PMID- 9517116
TI  - [Blood flow measurements with the laser Doppler anemometer in the highly stenosed
      carotid bifurcation].

PMID- 9517117
TI  - [Using ultrasound biomicroscopy in the mouth cavity for in vivo diagnosis of
      mucous membrane diseases].

PMID- 9517118
TI  - [Diagnostic possibilities of 3-dimensional imaging of ultrasound image data in
      mouth-, jaw- and facial surgery].

PMID- 9517120
TI  - [Phase-sensitive modulation thermography as a new method for non-contact in vitro
      measurement of the human tooth].

PMID- 9517119
TI  - [Determining local lung ventilation by functional electrical impedance tomography
      under clinical circumstances].

PMID- 9517121
TI  - [Noninvasive detection of blood spectra by time resolved in vivo spectroscopy].

PMID- 9517122
TI  - [Diagnostic method for determining the penetration behavior of cosmetics and
      drugs into the skin].

PMID- 9517123
TI  - [Thermostatically controlled coagulation probe for laser-induced interstitial
      thermotherapy].

PMID- 9517125
TI  - [Therapy of peri-implant inflammation with the CO2 swift laser system. An in
      vitro and in vivo study].

PMID- 9517124
TI  - [Use of the neodymium YAG laser 1064 in endoscopic thoracic surgery in the
      newborn infant and child].

PMID- 9517126
TI  - [Measuring optical tissue data using pulsed photoacoustic spectroscopy (PPAS)].

PMID- 9517127
TI  - [Holmium:YAG laser as an ablation device. Tissue changes in the rabbit brain
      after laser irradiation].

PMID- 9517128
TI  - [The Er:YAG laser--a new versatile instrument for (micro-) surgical
      applications].

PMID- 9517129
TI  - [Patient screening for MRI with SQUID biomagnetometers].

PMID- 9517130
TI  - [Noise signal suppression using frequency-dependent gradiometer factors
      exemplified by magnetocardiograms].

PMID- 9517131
TI  - [Current wave reconstruction with a physical thoracic phantom using magnetic
      field and body surface potential mapping].

PMID- 9517132
TI  - [Determining the magnetic heart vector].

PMID- 9517133
TI  - [Bicycle ergometric stress in healthy probands: differences between
      magnetocardiography (2-plane measurement) and electrocardiography].

PMID- 9517134
TI  - [De-magnetization procedures within the scope of biomagnetic diagnosis].

PMID- 9517135
TI  - [Magnetic measurement of local transit time in the small intestine].

PMID- 9517136
TI  - [Quantification of brain shift effects in MRI images].

PMID- 9517137
TI  - [Dissipative image data reduction of digital coronary angiograms: comparison of
      image quality by an objective parameter].

PMID- 9517138
TI  - [Quantitative analysis of the vascular diameter in coronary artery imaging using
      electron beam tomography: phantom studies and comparison with coronary
      angiography].

PMID- 9517139
TI  - [Simulation of a displacement current in the operating room].

PMID- 9517140
TI  - [Comparison of pulsed duplex ultrasound and high resolution laser Doppler
      anemometry for measuring intermittent flow fields].

PMID- 9517141
TI  - [Simulation of blood flow for validation of international reference values].

PMID- 9517142
TI  - [An improved thermo-provocation method for diagnosis of acral circulatory
      disorders].

PMID- 9517143
TI  - [Multiple sensor systems for online analysis of cellular signals: the
      PhysioControl microsystem].

PMID- 9517145
TI  - [Principles and special problems in calibration of fetal pulse oximetry].

PMID- 9517144
TI  - [Evaluation of hemodynamic sensors for implantable defibrillators].

PMID- 9517146
TI  - [Effect of electrode size on stimulus threshold in pacemaker stimulation].

PMID- 9517148
TI  - [Validation of control circuit behavior in frequency-adapted stimulation by
      interference responses].

PMID- 9517147
TI  - [Correlations of heart rate and AV time to degree of performance: significance
      for the dromotropic pacemaker concept].

PMID- 9517149
TI  - [Stimulation early after-depolarization-induced reentry mechanisms for developing
      anti-tachycardic therapy algorithms].

PMID- 9517150
TI  - [Methods for studying wear and parameters influencing wear characteristics of
      material combinations for hip endoprostheses].

PMID- 9517151
TI  - [Wear characteristics of knee joint axes].

PMID- 9517153
TI  - [Development of a simulator for evaluation of artificial hip joints].

PMID- 9517154
TI  - [Development of control strategies for standing up with a neuroprosthesis].

PMID- 9517152
TI  - [Computer-assisted test bench marking control of gait simulators].

PMID- 9517155
TI  - [Concepts for diagnostic support in quiet breathing spirometry in infants].

PMID- 9517156
TI  - [Noninvasive determination of tracheal pressure in ventilated children--a model
      study].

PMID- 9517157
TI  - [Interference suppression in biomedical signals, illustrated with the example of
      diaphragmatic electromyography].

PMID- 9517158
TI  - [Early detection of obstructive sleep apnea by statistical analysis of phase
      angle changes in respiratory tract impedance].

PMID- 9517159
TI  - [Analysis of discontinuous lung sounds by wavelet transformation and illustration
      of rare continuous oscillations].

PMID- 9517160
TI  - [Determination of mass inertia of the respiratory system--a model study].

PMID- 9517161
TI  - [Objective measurement of work of breathing with CPAP and BiLEVEL ventilation].

PMID- 9517162
TI  - [Surgery planning and implementation in computer-assisted surgery].

PMID- 9517163
TI  - [Current status of the development of a coronary vessel model for comparative
      studies of PTCA catheters].

PMID- 9517165
TI  - [3D finite element model of the cochlear amplifier].

PMID- 9517164
TI  - [In vitro comparison of various single and multi-ligators for treatment of
      esophagogastric varices].

PMID- 9517166
TI  - [On the way to an automatic heart-lung machine: a control system for oxygen
      tension in the oxygenator].

PMID- 9517167
TI  - [Absorption spectroscopy method for measuring 13C/12C isotope relations].

PMID- 9517169
TI  - [New pathways in tissue diagnosis].

PMID- 9517168
TI  - [Developing an optical calibrator for commercial pulse oximetry].

PMID- 9517171
TI  - Synchronous-detection reflection fluorometer for measurement of porphyrin
      concentration in biological tissues.

PMID- 9517170
TI  - [Improvement of an electromagnetic articulograph for registering tongue and lip
      movements].

PMID- 9517172
TI  - [Parameter extraction from intravenous ultrasound echo data for tissue
      identification].

PMID- 9517173
TI  - [Microsurgical erbium YAG system for use in ophthalmology].

PMID- 9517174
TI  - [Laser lithotripsy of complicated gallstones with a rhodamine 6G dye laser and
      automatic optical calculus-tissue detection system--results of 60 patients].

PMID- 9517175
TI  - [Frequency-doubled double pulse Nd:YAG laser (FREDDY) for gallstone lithotripsy-
      preclinical and initial clinical results].

PMID- 9517177
TI  - [Applicator development and irradiation planning in laser-induced thermotherapy
      (LITT)].

PMID- 9517176
TI  - [Basic studies of a piezo-acoustic stone-tissue recognition system for laser
      lithotripsy of gallstones].

PMID- 9517178
TI  - [EASIE-Erlangen Education Simulation Model for Interventional Endoscopy--a new
      bio-training model for surgical endoscopy].

PMID- 9517179
TI  - [Effects of the substructure of trabecula on failure of spongiosa bones].

PMID- 9517180
TI  - [Numerical and experimental analysis of initial tooth mobility].

PMID- 9517181
TI  - [Numerical simulation of orthodontic tooth movements using the finite element
      method (FEM)].

PMID- 9517182
TI  - [Visualization of medical data using the Dresden Autostereoscopic Display].

PMID- 9517183
TI  - Evaluation of programs for 3D-visualization of serial sections monitored by non
      invasive optical tomography.

PMID- 9517184
TI  - [Analysis of gaze orientation in an integrated signal for monitoring
      hemodynamics].

PMID- 9517185
TI  - [Flight orientation trainer--possibilities and planned application in the air
      force].

PMID- 9517186
TI  - [Accuracy of stereolithographic models for surgery planning].

PMID- 9517187
TI  - [Mask technique of the BrainLab Company. Noninvasive fixation in stereotaxic
      radiotherapy].

PMID- 9517188
TI  - [Aerosol beam coagulator--a new device for contact-free soft coagulation].

PMID- 9517189
TI  - [Measuring breath alcohol concentration during artificial ventilation. Model
      studies of the effect of temperature and humidity on the reproducibility of
      measurements of various sampling systems].

PMID- 9517190
TI  - [How can customized modifications of medical products for research purposes be
      legally manufactured in compliance with the Medical Products Regulation?].

PMID- 9517191
TI  - [New materials in tumor endoprosthetics].

PMID- 9517192
TI  - [Possibilities and indications for carbon fiber reinforced synthetic materials
      for designing individual implants for reconstruction of the facial bones and
      skull].

PMID- 9517193
TI  - [The mini-screw spindle pump: development of an implantable nonpulsatile blood
      pump for assisted circulation].

PMID- 9517194
TI  - [Effect of titanium surfaces of various roughness on cell proliferation, cell
      differentiation and protein synthesis of human fetal osteoblasts (hFOB 1.19)].

PMID- 9517195
TI  - [Biological and physical evaluation of the functional materials glass and silicon
      for micromechanical effectors].

PMID- 9517196
TI  - [Viscoelastic properties of human capsular sac contents].

PMID- 9517197
TI  - [Wavelet analysis of acoustically evoked potentials during repeated propofol
      sedation].

PMID- 9517198
TI  - [Field theoretical calculation of the monophasic action potential for optimizing
      implantable electrodes].

PMID- 9517199
TI  - [3D visual evoked potential detection with circular T2 statistics].

PMID- 9517200
TI  - [Visual evoked potential bispectral analysis using robust distribution
      classification].

PMID- 9517201
TI  - [Determined signal responses in visually evoked stimulus responses].

PMID- 9517202
TI  - [Hyperthermic treatment of tumor tissue using iron(II,III)-oxide].

PMID- 9517203
TI  - [Simulation of hyperthermia based on voxel-based volume models].

PMID- 9517204
TI  - [Intracavitary high frequency thermotherapy--first trials in the cattle liver
      model].

PMID- 9517205
TI  - [Stomach involvement in systemic scleroderma--prospective electrogastrographic
      and ultrasound study].

PMID- 9517206
TI  - [Nanoscope and application examples for the study of biological structures].

PMID- 9517207
TI  - [Evaluation of regional and global heart function and heart metabolism in
      hemoperfused swine hearts].

PMID- 9517208
TI  - [An application program for determining stroke volume in the catheter
      laboratory].

PMID- 9517209
TI  - Application of branched electrodes for stable, selective recording single motor
      unit discharges in humans.

PMID- 9517211
TI  - [Eye-hand interactions in elderly research probands and in Parkinson patients].

PMID- 9517210
TI  - [Construction and modeling of a physical thoracic phantom for magnetic field and
      body surface potential mapping].

PMID- 9517212
TI  - [Evaluation system for collecting diagnostic information from signals and data of
      medical sensor systems].

PMID- 9517213
TI  - [Bioactive ceramics substance for reconstruction of bone tissue].

PMID- 9517214
TI  - [Biomechanical, biological and technological principles in treatment of bone
      fractures].

PMID- 9517215
TI  - [Bispectral analysis of neonatal EEG patterns].

PMID- 9517216
TI  - [Burst detection in EEG monitoring of intensive care patients].

PMID- 9517217
TI  - [Computer-assisted orthodontic treatment planning and analysis of treatment
      situations].

PMID- 9517218
TI  - [Computer modelling of the rigidity of external fixators].

PMID- 9517219
TI  - [Presentation of three-dimensional echocardiography with the Dresden
      autostereoscopic display].

PMID- 9517220
TI  - [Effect of angiographic projection of blood vessel and calibration catheter on
      accuracy of quantitative coronary angiography].

PMID- 9517221
TI  - [Use of the Hilbert operator for determining absorption differences between
      retinal blood vessels and their surroundings].

PMID- 9517222
TI  - [Effective forces during walking on the human hip acetabulum].

PMID- 9517224
TI  - [Three-dimensional image analysis for the study of spastic movement disorders].

PMID- 9517223
TI  - [Impedance spectroscopy, a method for monitoring cellular vitality
      (biosensoring)].

PMID- 9517225
TI  - [Real time analysis of arm rotation during walking with the 3D Optotrak System].

PMID- 9517226
TI  - [EEG/MEG source localization in local stimulation of the retina].

PMID- 9517227
TI  - [A fuzzy evaluation program for the PTCA catheter].

PMID- 9517228
TI  - [A modular multichannel stimulator for producing stimulus pulses of selected wave
      form for experimental and clinical use].

PMID- 9517229
TI  - [Effect of molecular weight and protein coating of surface properties of
      poly(beta-hydroxybutyric acid) and the effect on polymer-cell interaction].

PMID- 9517230
TI  - Experiences with local photodynamic therapy with TPPS4 and non-coherent light.

PMID- 9517231
TI  - [Flexible multichannel microelectrodes with integrated leads for use in
      neuroprosthetics].

PMID- 9517232
TI  - [Vascular segmentation with fuzzy and standard methods].

PMID- 9517233
TI  - [Accuracy and precision of analytical calibration in quantitative coronary
      angiography].

PMID- 9517234
TI  - [Equilibrium studies--a comparison of measuring results of a force measuring
      plate and ultrasound movement analysis system].

PMID- 9517235
TI  - [Identification of diencephalic structures using computer-assisted signal
      analysis of intracerebral potential registration].

PMID- 9517236
TI  - [Conception and development of flexible stimulator structures within a retinal
      implant system].

PMID- 9517237
TI  - [Conception and realization of a sensory system for detection of accidental
      falls].

PMID- 9517238
TI  - [Measuring electromagnetic fields at work sites].

PMID- 9517239
TI  - [Model developments for calculating force systems for orthodontic treatment
      elements].

PMID- 9517240
TI  - [Model studies of impulse oscillometry in newborn infants].

PMID- 9517241
TI  - [Possible values for characterization of pulse generation in the peripheral
      vascular circulation of the human].

PMID- 9517242
TI  - [New methods for improving the image quality of functional electric impedance
      tomography].

PMID- 9517243
TI  - [Noninvasive blood pressure measurement in external counterpulsation].

PMID- 9517244
TI  - [Optimizing MRI sequences for measuring temperature in extremity muscles].

PMID- 9517245
TI  - Peripheral nerve stimulation in vitro using excentrical coils with improved
      spatial resolution.

PMID- 9517246
TI  - Quantitative assessment of phase entrainment between discrete and cyclic motor
      actions.

PMID- 9517248
TI  - [Assessment of catheter drive and measurement collection in a coronary vessel
      model for the PTCA catheter].

PMID- 9517247
TI  - [Scanning probe microscopy as a test procedure for coated hydrophilic silicone
      biomaterials].

PMID- 9517249
TI  - [Development of an improve reciprocal walking orthosis for children with spina
      bifida].

PMID- 9517250
TI  - [Reconstruction of marker positions with redundant markers in gait analysis with
      the 3D Optotrak System].

PMID- 9517251
TI  - [Rapid proton radiography with the proton-gantry of the Paul Scherrer Institute].

PMID- 9517252
TI  - [Selective activation of the bladder with quasi-trapezoidal pulses in sacral
      anterior root stimulation in the dog].

PMID- 9517253
TI  - [Spectral transmission and absorption behavior of living standard cells in the
      area of visual and near infrared light].

PMID- 9517254
TI  - [Speed band multi-ligature of esophagogastric varices--results of 159 acute and
      elective treatments in 60 patients].

PMID- 9517255
TI  - [Stimulation-induced brain electrical oscillations in healthy probands].

PMID- 9517256
TI  - [Dead space-free ventilation measurement in artificial respiration of newborn
      infants].

PMID- 9517257
TI  - [Structure-phase status and mechanical properties of bioinert layers on titanium
      alloys].

PMID- 9517258
TI  - [Changes in dynamic flow resistance in single pulse conditions of the peripheral
      vascular system in the human].

PMID- 9517259
TI  - [Using a matrix as the basis for a series of data].

PMID- 9517260
TI  - [Fully automatic vascular segmentation with morphological filter, skeletal
      structure and region growing exemplified by photographs of chick embryos].

PMID- 9517261
TI  - [Preparation of hydroxyapatite powder for coating biomechanical surfaces by
      plasma spraying].

PMID- 9517263
TI  - [Innovations for health: contribution of biomedical techniques].

PMID- 9517262
TI  - [Embolism detection in transcranial Doppler ultrasound--most recent technical
      developments].

PMID- 9517264
TI  - [The role of synergetics in biofluid mechanics: added theoretical foundation for
      explaining central aspects of biology, athermoma development and thrombosis].

PMID- 9517265
TI  - [Time-dependent mechanical stimulation of enchondral fracture healing in the
      sheep].

PMID- 9517266
TI  - [Digital radiography].

PMID- 9517267
TI  - [Radionuclide therapy].

PMID- 9517268
TI  - [Circadian fluctuations of the signal-averaged electrocardiography].
AB  - Circadian periodicity for the time of onset of acute myocardial infarction has
      been shown; the early morning peak of infarction coincides with the onset of
      other related phenomena, including sudden cardiac death, ventricular arrhythmias,
      thrombotic stroke, etc. Late potentials detected by the signal-averaged ECG are
      considered to be independent markers of vulnerability to ventricular arrhythmias.
      The signal-averaged ECG enables the amplifying and recording of small bioelectric
      signals of cardiac origin, while eliminating extraneous electrical "noise." To
      determine whether late potentials are themselves subject to circadian influence,
      31 patients (age range 41-79) who had had an old or recent myocardial infarction
      underwent late potential assessment by the signal-averaged ECG. 4 indices were
      studied: duration of late LPD potentials (LPD), total QRS duration (TQRS), and
      root mean square voltage of the last 40 msec, and of the last 50 msec (RMS 40 and
      RMS 50). These indices were assessed 3 times, during the early morning hours, at
      noon and during the evening. Morning LPD differed significantly from noon and
      evening LPD and the morning RMS 40 similarly differed from noon and evening
      values. TQRS and RMS 50, even though remaining in the normal range, also showed a
      tendency to abnormal values during morning hours. These findings could possibly
      be related to the early morning incidence peaks of severe ventricular arrhythmia
      and sudden cardiac death, since abnormal late potentials constitute the
      physiopathological basis for certain ventricular arrhythmias.

PMID- 9517269
TI  - [Progression of diabetic retinopathy after cataract extraction].
AB  - A prospective study of the effect of cataract extraction with intraocular lens
      implantation on the course of diabetic retinopathy (DR) in 44 patients (59 eyes)
      was carried out. It showed that in the 1-3 years following surgery, there was
      progression of DR (including development of newly formed retinopathy) in 35% of
      the patients (28.8% of eyes). Progression was more marked in patients with pre
      operative bilateral DR compared to those without bilateral DR (77% and 16%
      respectively). Insulin dependence did not play a role in progression. Final
      visual acuity was better in patients without pre-operative DR, as well as in eyes
      without progressive retinopathy.

PMID- 9517270
TI  - [Continuous quality improvement in anesthesia].
AB  - Slow continuous quality improvement (SCQI) in anesthesia is a process that allows
      identification of problems and their causes. Implementing measures to correct
      them and continuous monitoring to ensure that the problems have been eliminated
      are necessary. The basic assumption of CQI is that the employees of an
      organization are competent and working to the best of their abilities. If
      problems occur they are the consequences of inadequacies in the process rather
      that in the individual. The CQI program is a dynamic but gradual system that
      invokes a slower rate of response in comparison with other quality methods, like
      quality assurance. Spectacular results following a system change are not to be
      expected an the ideal is slow and continuous improvement. A SCQI program was
      adapted by our department in May 1994, according to the recommendations of the
      American Society of Anesthesiologists. Problem identification was based on 65
      clinical indicators, reflecting negative events related to anesthesia. Data were
      collected using a specially designed computer database. 4 events were identified
      as crossing previously established thresholds (hypertension, hypotension, hypoxia
      and inadequate nerve block). Statistical process control was used to establish
      stability of the system and whether negative events were influenced only by the
      common causes. The causes responsible for these negative events were identified
      using specific SCQI tools, such as control-charts, cause-effect diagrams and
      Pareto diagrams. Hypertension and inadequate nerve block were successfully
      managed. The implementation of corrective measures for the other events that
      cross the threshold is still in evolution. This program requires considerable
      dedication on the part of the staff, and it is hoped that it will improve our
      clinical performance.

PMID- 9517271
TI  - [Gentamycin distribution volume in a mechanically ventilated patient--
      pharmacokinetic and clinical aspects].
AB  - Mechanical ventilation (MV) of more than 32 hours may alter the gentamycin
      pharmacokinetic profile by increasing its volume of distribution (VD). As a
      result, the standard garamycin dosage regime has to be adjusted in order to
      obtain an adequate peak serum concentration, which is well correlated with the
      efficacy of garamycin therapy. Garamycin is a water-soluble drug with negligible
      binding to plasma albumin, so its VD approximates the volume of extra-cellular
      fluid, which may be expanded by MV. MV-related fluid retention is mediated via
      various homeostatic compensatory systems. They are activated to combat the
      decrease in cardiac output and central blood volume caused by MV, due to the
      increase in airway and intrathoracic pressure. These phenomena are more prominent
      during prolonged ventilation, PEEP or C-PAP ventilation, and in previously
      hypovolemic patients. Patients requiring MV for more than 32 hours had an average
      garamycin VD of 0.36 L/Kg compared with the mean VD of 0.25 L/Kg in normal
      adults. In the patient presented, a similar change in garamycin VD was seen,
      while conventional doses given during MV failed to reach suitable clinical peak
      levels.

PMID- 9517272
TI  - [Incidence, antimicrobial resistance and mortality in bloodstream infections in
      the critically ill].
AB  - Bloodstream infections (BSI) are 7-fold more common in patients admitted to the
      intensive care unit (ICU) rather than to other hospital wards. The epidemiology
      of BSI in critically ill patients in Israel has not been systematically
      addressed. We examined the annual trends in BSI in patients in a general ICU of
      evolving patterns of antimicrobial resistance and associated mortality rates for
      the years 1994-1996. The presence of the systemic inflammatory response syndrome
      (SIRS) when the first positive blood cultures are taken was a prerequisite for
      its definition as clinically significant. The unit site, staff, practice
      guidelines, and type of patient were unchanged during the study period. Blood
      cultures were positive in 220.7-332.0 patients per 1000 ICU admissions, 18-22
      fold more common than in regular ward patients. SIRS was a universal finding in
      these ICU patients. There was multi-drug resistance for the majority of species
      cultured, reaching 100% in some cases. Crude hospital mortality of ICU patients,
      with and without positive blood cultures, was 31-54% and 5-14%, respectively. The
      introduction of a new blood culture system (Bactec 9240) in 1996 was associated
      with a 61% increase in the rate of patients with positive blood cultures,
      accounted for mostly by increased isolation of coagulase-negative staphylococci.
      However the mortality rate for the latter decreased by 59%, suggesting the
      possibility of a selective increase in detection of contaminated cultures.
      Although highly prevalent in the study population and generally defining a
      patient group with high mortality risk, the specificity of SIRS-associated
      positive blood cultures may be species and culture-system dependent. These
      findings re-emphasize the need for both improved control measures for the
      epidemic proportions of BSI and multi-drug antimicrobial resistance, as well as
      more specific indicators of the clinical relevance of positive blood cultures in
      critically ill patients.

PMID- 9517273
TI  - [Percutaneous ablation of malignant kidney tumors in rabbits by low frequency
      radio energy].
AB  - Radio-frequency (RF) current has been used successfully to ablate normal human
      tissue. To investigate further the clinical application of this modality in
      tumors, we studied the potential of using RF percutaneously to destroy
      experimental kidney tumors. 35 outbred albino rabbits underwent direct
      implantation of renal VX2 tumor during open surgery. After 21 days,
      ultrasonography was performed to show tumor presence and size. A shielded RF
      needle was designed to be inserted percutaneously through an introduction needle.
      An electrical insulation shield covering the RF needle was retractable,
      controlling the length of exposure of the RF needle inside the tissue. 22 days
      after tumor implantation, RF was applied via this special needle using a ZoMed
      International RF generator. In one group of rabbits the procedure was performed
      under direct vision during open surgery, while in another group treatment was
      percutaneous, the needle guided by palpation of the tumor. Rabbits were killed 3
      days later and revealed 4-25 mm intra-tumoral RF-induced lesions. A direct
      relation was found between lesion size and the power and duration of RF applied
      (at 7.5 W, R = 0.48, and P = 0.32). Based on our preliminary results we can
      conclude that RF may have clinical applications in the near future for
      percutaneous local tumor control in parenchymal organs.

PMID- 9517274
TI  - [Conservative approach in children with central line infection].
AB  - In 1994-1995, central venous lines were placed in 47 children. All except 1 were
      of the Broviac type, with subcutaneous tunneling via the internal or external
      jugular vein. Ages were between 7 days and 16 years. Indications for central
      venous cannulation were chemotherapy (35 cases), TPN (5), prolonged parenteral
      antibiotics (4), and repeated blood transfusions (3). The catheter was the source
      of infection in 13 children (28%), 11 of whom were immunocompromised. The
      commonly identified bacteria were Staphylococcus aureus (4 cases), Pseudomonas
      aeruginosa (4), coagulase-negative Staphylococcus (2), and various gram-negative
      rods (3). All cases were treated with antibiotics through the catheter. The most
      commonly used were oxacillin (4), ceftazidime (4), and amikacin (4). In 10,
      treatment succeeded without having to remove the line. In 2 others, tunnel
      infection developed and the catheter had to be removed. 1 child forcefully
      removed his catheter before treatment could be started. There were no further
      complications in the group treated conservatively, except for a case of superior
      vena cava thrombosis in a girl with recurrent infection of the tunnel. In 7 out
      of 13 treatment was continued and completed at home. This saved 65 days of
      hospitalization out of 210. We conclude that the conservative approach to
      treatment is feasible in most cases of infection when the source is the central
      venous catheter itself. However, when the tunnel is infected, conservative
      treatment may be ineffective. Treatment can be carried out in the home, with
      economy in cost and in use of hospital beds, and is preferred by patients and
      their parents.

PMID- 9517275
TI  - [Fungus-ball in a preterm infant successfully treated with fluconazole].
AB  - Very-low-birth-weight premature infants are at high risk for invasive
      candidiasis. The most commonly involved organ is the kidney. Renal candidiasis
      may present as fungus-ball obstructive uropathy. We describe unilateral renal
      obstruction secondary to fungus-ball in a premature infant. Noninvasive, systemic
      antibiotic treatment, including amphotericin B and fluconazole, resulted in
      disappearance of the finding.

PMID- 9517276
TI  - [Onchocerca volvulus--a rare cause of a mass in children].
AB  - The parasite Onchocerca volvulus is well-known in its endemic areas in South and
      Central America and West Africa. It is transmitted to man by simulium flies and
      causes systemic infection with skin, lymphatic and ophthalmic manifestations and
      can cause blindness (river blindness). Treatment with Ivermectin is effective but
      sometimes there is need for surgical intervention to prevent or treat
      complications. We describe an 11-year-old girl, a new immigrant from Ethiopia,
      who had a firm mass in her left thigh, caused by Onchocerca volvulus. It was
      completely excised. This is a very rare condition in Israel, which must be
      considered in patients coming from endemic areas.

PMID- 9517277
TI  - [Local treatment of purulent chronic otitis media with ciprofloxacin].
AB  - We evaluated the efficacy of ciprofloxacin eardrops compared to tobramycin and to
      a placebo in the treatment of chronic suppurative otitis media. 60 ears were
      randomly assigned to treatment for 3 weeks with ciprofloxacin, tobramycin or
      placebo eardrops. The organism most commonly isolated from the ear discharge was
      Pseudomonas aeruginosa. The clinical responses were 78.9% and 72.2%,
      respectively, in the ciprofloxacin and tobramycin groups, while it was only 41.2%
      in the placebo group. Treatment with ciprofloxacin eardrops seemed to be at least
      as efficient as treatment with tobramycin. Considering the lack of ototoxicity of
      ciprofloxacin, this treatment may be best for chronic otitis media.

PMID- 9517278
TI  - [Verapamil-associated liver injury].
AB  - Hepatotoxicity due to verapamil is very rare and to the best of our knowledge
      only 10 cases have been reported. A 54-year-old woman developed cholestatic liver
      injury and pruritus following treatment with sustained-release verapamil (240
      mg/day) for arterial hypertension. The pruritus and all hepatic biochemical
      abnormalities completely resolved after withdrawal of the drug. Similar to
      previously reported cases, the pathogenic mechanism of verapamil-associated liver
      injury in our patient was, most probably, idiosyncratic. These cases emphasize
      the need for awareness of the possibility that verapamil may occasionally induce
      liver injury, sometimes severe and potentially fatal.

PMID- 9517279
TI  - [The internet and anesthesia].

PMID- 9517280
TI  - [Obstructive sleep apnea and hypertension].

PMID- 9517281
TI  - [Persistent pulmonary hypertension of the newborn--new modes of therapy].

PMID- 9517282
TI  - [Chronic urticaria--update].

PMID- 9517283
TI  - [Hypotension-hypertension laboratory].

PMID- 9517284
TI  - [Cultural aspects of eating disorders].

PMID- 9517285
TI  - [The first 75 years of the Hadassah-Rothschild-Bnei-Zion Hospital, Haifa].

PMID- 9517286
TI  - [Their finest hour: Jewish physicians and health workers in Eretz Israel during
      the First World War].

PMID- 9517287
TI  - [Patients' opinions of the role of primary care physicians and the organization
      of health care services].
AB  - Patients' opinions of the role of the primary care physician were studied. The
      study population consisted of Hebrew-speaking members of the Clalit Sick Fund,
      aged 18+, who visited primary care and specialty clinics. Interviews took place
      during January-March 1995 in the Emek and Jerusalem, and during August-October
      1995 in Beer Sheba. A total of 2,734 interviews were conducted, and the response
      rate was 88%. 64% of the respondents preferred the primary care physician as the
      first address for most problems occurring during the day. Multivariate analysis
      revealed that the variables predicting this reference were: being over age 45,
      having completed less than 12 years of schooling, being satisfied with the
      physician, and when a child's illness was involved. Whether the physician was a
      specialist had only a marginal effect. The findings also show that among those
      who did go directly to a specialist for the current visit, 49% would still prefer
      the primary care physician to be the first address for most problems. However,
      half of the respondents initiated the current visit to the specialty clinic
      themselves. The findings also showed that a preference for the primary care
      physician to be the first address had an independent and statistically
      significant effect on the following aspects of service consumption: taking the
      initiative to go to a specialist, the intention to return to the primary care
      physician or to the specialist for continuing care, and the patient's belief that
      referral to a specialist was needed. The findings of the study may be of
      assistance to policy-makers on the national level and to sick funds in planning
      the role of the primary care physician, so that it corresponds, on the one hand,
      to the needs of the sick funds and the economic constraints in the health system,
      and on the other, to the preferences of the patient.

PMID- 9517288
TI  - [Accessibility of information and informed consent: experiences of breast cancer
      patients].
AB  - We studied the social and cultural frameworks that impact on breast cancer
      patients in the medical system. The subjects were 98 Jewish women who had
      undergone mastectomy or lumpectomy for cancer 6 months to 3 years prior to the
      interview. They emanated from a variety of socioeconomic and ethnic backgrounds,
      and reflected the age range of women with breast cancer in the general Jewish
      population of Israel. Patients were asked about each stage of the medical process
      they had experienced: diagnosis, surgery, oncological care, and follow-up care.
      The interview revealed a general perception of having received insufficient
      information regarding their medical condition and treatment. The problem tended
      to be most severe during the diagnostic stage, when women had not yet been
      officially included as patients within the system. The problem was relatively
      severe during follow-up care, when they often did not have an address for their
      questions. Few women received a schedule of follow-up care that allowed them to
      carry on with the many necessary tests in an orderly and comprehensive manner.
      Most important, systematic absence of informed consent also characterized the
      decision-making process regarding surgery and oncological treatment. Few women
      felt they had been informed about treatment options, side-effects, or long-term
      implications of the treatment offered. We found no indication of inequitable
      medical treatment that would suggest a manifest pattern of discrimination, but we
      did find some social variables related to a feeling of insufficient personal care
      and information. In particular, older women said they received less attention,
      support, and information from the medical staff relative to the younger women.

PMID- 9517289
TI  - [Mixed uterine mesodermal sarcoma in the population of southern Israel in the
      years 1996-1971--clinical and pathological characteristics].
AB  - During 1971-1996, 17 patients with mixed mesodermal uterine tumors were treated.
      Average age at diagnosis was 67.3 years, 12/17 were of European and 5/17 of Afro
      Asian extraction. The overall 5-year survival was 21%. 10/17 patients had mixed
      mesodermal tumors with a heterologous mesenchymal element, and 7/17 had a
      homologous mesenchymal element (carcinosarcoma). 6/17 had another primary
      malignancy, including breast cancer (3/17), bilateral metachronous breast tumor
      (2/17), and malignant lymphoma of the neck region (2/17). All 3 with breast
      cancer had previously been treated with tamoxifen. I had simultaneous mesodermal
      tumor and ovarian thecoma. Simultaneous autoimmune manifestations occurred in
      2/17, including thrombocytopenic purpura in 1, and myasthenia gravis in another.
      Mesodermal tumor of the uterus is a relatively rare malignancy with aggressive
      behavior and poor prognosis. It also had unusual associations with other primary
      tumors, hormonal treatment, and autoimmune manifestations.

PMID- 9517290
TI  - [Are testes in oligo/azoospermia homogenous or heterogenous?].
AB  - We determined whether a single testicular specimen is sufficient to represent
      qualitatively the spermatogenic process within the testes of azoospermic or
      severely oligospermic infertile men. In 191 testes of azoospermic patients and in
      26 of those with severe oligospermia, fine needle aspirations at 3 different
      sites of each testis were performed. Aspirated material from each puncture was
      stained and in each smear all spermatogenic cells, as well as Sertoli cells, were
      identified. Testes were classified according to the most mature spermatogenic
      cell type present, or the presence of only Sertoli cells. The homogeneity of the
      testicular spermatogenic process was then evaluated. There was an overall
      intratesticular difference between aspirates in 14.1% of azoospermic testes and
      in 26.9% of severely oligospermic testes with regard to the most mature
      spermatogenic cell type. When spermatozoa were the most mature cell type, they
      were detected in all of the 3 aspirates in 71.4% of the testes. In 18.4% or 10.2%
      of this group of testes they were retrieved in only 1 or 2 of the aspirates,
      respectively. In testes in which spermatids or spermatocytes were the most mature
      spermatogenic stage, these cell types were detected in all 3 aspirates in only
      36.4% and 68.0%, respectively. In azoospermic patients with full testicular
      spermatogenesis, the likelihood of retrieving spermatozoa from the testes was
      84.3%, 92.7% and 100% in 1, 2 and 3 specimens, respectively. The following
      conclusions were drawn: There is a wide range of testicular heterogeneity in
      azoospermia or very severe oligospermia for diagnosing the testicular
      spermatogenic pattern. In azoospermia, specimens from several testicular sites
      are required. It is strongly recommended that no assisted fertilization be
      offered to azoospermic patients unless prior evaluation of the spermatogenic
      pattern in the seminiferous tubules is determined.

PMID- 9517291
TI  - [First year's experience of the Post-Operative Cardiac Care Unit, Schneider
      Children's Medical Center].
AB  - In the past 10 years there has been a growing preference for early, complete
      correction of congenital heart disease. The first year of operation of this
      cardiac unit is described. 216 operations were performed: 15% in the neonatal age
      group and 35% in the newborn to 1-year-old groups; 2% were palliative procedures.
      Mortality was 4.9%. Average stay in the ICU was 3.2 days, with a median of 2.25.
      Average length of ventilation was 35 hours, with a median of 17.5. Complications
      were: diaphragm paralysis in 13 (6%), 2/3 of which were recurrent operations; in
      2 patients (0.9%) we had to plicate the diaphragm. There was severe neurological
      damage in 2 which deteriorated to brain death in 1. There was peripheral,
      reversible neurological damage in 4 (1.8%), and acute renal failure in 3%, with
      half of them requiring dialysis. 75% of these children died and there was
      superficial infection in 4.1%, deep wound infection in 1.3%, bacteremia in 4.1%,
      superior vena cava syndrome in 3 (1.3%) and chylothorax in 2 of them (0.9%). 1
      patient (0.45%) required a ventricle-peritoneal shunt after acute viral
      meningitis. We are encouraged by our results to offer early complete correction
      to all children with congenital heart disease.

PMID- 9517292
TI  - [Closed intramedullary nailing of forearm fractures in young patients].
AB  - Forearm bone fractures are commonly the result of falling on the outstretched
      hand or of direct injury. The preferred treatment is debated. The possible
      modalities are: application of a cast, often necessitating repeated
      manipulations; open reposition and fixation by plates and screws; or closed
      manipulation and closed intramedullary nailing. We present our favorable results
      in treating these fractures in young patients by closed intramedullary nailing,
      and compare them with the unfavorable results of this method in mature adults.

PMID- 9517294
TI  - [Telemedicine--possibilities, impediments and forecast].

PMID- 9517293
TI  - [Six cases of acute rheumatic fever in one year].
AB  - During 1995, 6 cases of acute rheumatic fever were diagnosed here. Taking into
      account differences in total admissions, this appears to represent an increase
      over 1994. Most of the cases were males, with average age at diagnosis 19.5
      years. All were of low socioeconomic status. 50% had cardiac involvement, and 1
      needed treatment with corticosteroids. Most had pharyngeal symptoms prior to the
      acute attack, and 1 patient had 2 prior episodes of rheumatic fever. A thorough
      epidemiological study should be done in the Nazareth area to assess the real
      incidence of acute rheumatic fever, and to determine whether there is a true
      increase in incidence.

PMID- 9517295
TI  - [Munchausen's syndrome--the present situation].

PMID- 9517296
TI  - [A new hepatitis virus; will the letters of the alphabet suffice?].

PMID- 9517297
TI  - [The role of calcium in brain ischemia and trauma--1997].

PMID- 9517298
TI  - [Sialography in the diagnosis of salivary gland lesions].

PMID- 9517299
TI  - [Rectal diazepam for treatment and prevention of seizures in children].

PMID- 9517300
TI  - [Noncardiac use of radiopharmaceuticals in oncology].

PMID- 9517301
TI  - [Traumatic pancreatic injuries].

PMID- 9517302
TI  - [Prostaglandins and termination of second trimester pregnancy].

PMID- 9517303
TI  - [Tuberculosis during pregnancy].

PMID- 9517304
TI  - [Clock-drawing test in dementia due to Alzheimer's disease].

PMID- 9517305
TI  - [Janusz Korczak in the eve of his life, his work in the shadow of terror and
      death].

PMID- 9517306
TI  - [Genetic information: whose property?].

PMID- 9517307
TI  - [A rare cause of urinary frequency].

PMID- 9517308
TI  - The influence of traditional values of education of Greek students' real and
      ideal self-concepts.
AB  - Students' real and ideal self-concepts were studied with respect to their
      acceptance or rejection of the traditional values of Greek education. The
      relationship between the real and the ideal components of self-concept was also
      examined. A sample of Athenian students who answered a questionnaire accepted
      most of the traditional values of education. The students' internalization of
      such values predicted their moderately satisfied real self-concepts and their
      extremely developed ideal self-concepts, which symbolized their hopes and
      ambitions for academic achievement. The factor-analyzed items of self-concept
      revealed a disparity between the real and the ideal components of the
      participants' self-concepts.

PMID- 9517309
TI  - Acceptance of disability and its correlates.
AB  - In a sample of 1,266 U.S. adults with disabilities, relationships were examined
      between acceptance of disability and (a) demographic characteristics (age,
      gender, race, education, marital status, and income); (b) disability conditions
      (disability onset, multiple disabilities, and chronic pain); and (c) other
      psychosocial factors (self-esteem, emotional support, perceived discrimination,
      and hostility). Self-esteem and emotional support from family and friends played
      important roles in the participants' adjustment to disability. Furthermore,
      perceived social discrimination against people with disabilities had a
      significant impact on acceptance of disability. Disability conditions such as
      acquired disability, multiple disabilities, and chronic pain were also important
      variables related to disability acceptance.

PMID- 9517311
TI  - Racial identity of children in integrated, predominantly white, and black
      schools.
AB  - Fourth-grade children in three school settings (integrated, Black, and White)
      were assessed by 3 methods: the Draw-A-Person test, the spontaneous self-concept
      test, and the picture test. The effect of school's population on a child's racial
      identity was studied. The children in the integrated school setting mentioned
      race and ethnicity significantly more often than did children in either of the
      other two settings. The children from both the integrated and the predominantly
      White schools also chose more friends from the outgroup than did the children in
      the predominantly Black school. The children in the non-integrated schools
      disliked other races more. All groups chose their own race when asked to indicate
      which child looked most like them. Contrary to the research hypothesis, the
      children in the predominantly White school produced drawings that depicted their
      race more obviously than did children from either of the other schools.

PMID- 9517310
TI  - Sex differences in marital and social adjustment.
AB  - A sample of 67 married Japanese men and 79 married Japanese women, ranging in age
      from 25 through 85 years, were interviewed to clarify the relationship between
      marital adjustment and social adjustment. For the whole sample, the total score
      of the Short Marital Adjustment Test (SMAT; Locke & Wallace, 1959) and its
      subcategories, dyadic consensus and satisfaction, was significantly correlated
      with 5 subcategory scores of the Social Adjustment Scale-II (SAS-II; Weissman,
      1978): household adjustment (except the spouse), external family adjustment, work
      adjustment, social leisure adjustment, and general adjustment. These correlations
      were present also for the women; for the men, they were present only for social
      leisure adjustment and general adjustment. Among men, the dyadic consensus scores
      of the SMAT had stronger correlations with the social adjustment scores; among
      women, correlations with the marital satisfaction scores of the SMAT were
      stronger. Thus, marital adjustment may be a part of social adjustment for women,
      but the two may be discrete for men.

PMID- 9517312
TI  - Gender differences in romantic jealousy.
AB  - Findings of studies of gender differences in jealousy are contradictory. In the
      present study, conflicting literature was addressed by distinguishing 5
      dimensions of jealousy: level, trigger, experience, focus, and responses. In 4
      studies, 3 in the U.S. and 1 in Israel, gender differences were explored in these
      5 dimensions of romantic jealousy. Although there were no gender differences in
      the likelihood, frequency, duration, or intensity of jealousy, there were
      differences in the responses to certain jealousy-producing occasions as well as
      in the focus, experience, and expression of jealousy.

PMID- 9517313
TI  - Perceptions of well-being among the older metropolitan and nonmetropolitan
      populations in the United States.
AB  - The relationships were examined between selected sociodemographic variables and
      perceptions of well-being among residents 60 years and older of metropolitan and
      nonmetropolitan areas in the United States. Multiple regression models were used
      in analyzing data from the 1982-1991 NORC General Social Survey. Such
      sociodemographic variables as gender, race, marital status, education, financial
      status, place of residence, religious membership, and religious attendance were
      independent variables. A composite score of perceptions of well-being was the
      dependent variable. Race, marital status, education, financial status, religious
      attendance, and place of residence were important to well-being; gender and
      religious membership were not significant. The effects of nonmetropolitan living
      also significantly enhanced perceptions of well-being. Other facets of mental
      health in metropolitan and nonmetropolitan areas were also examined.

PMID- 9517314
TI  - Personal need for structure and attitudes toward homosexuality.
AB  - The need of a sample of U.S. students to cognitively structure reality as
      measured by the Personal Need for Structure (PNS) Scale was examined as a
      predictor of attitudes toward homosexuality measured by the Attitudes Toward
      Lesbians and Gay Men (ATLG) Scale. Significant relationships between the two
      constructs and strong gender differences on the ATLG were found.

PMID- 9517315
TI  - The impact of perceptions and stereotypes on the managerial mobility of African
      Americans.
AB  - Although African Americans have made progress in reaching middle and upper
      management positions, a disproportionate number are stalled in lower levels of
      management where their remuneration often lags behind that of Whites in
      comparable positions. Further penetration into executive ranks may depend largely
      on the perceptions and attitudes of employers. Negative stereotypes held by top
      managers may have a deleterious effect on African American opportunities. Among a
      sample of White middle managers, Schein's (1973, 1975) descriptive index revealed
      a significant resemblance between ratings of Whites and ratings of managers (r' =
      .54), whereas the resemblance between ratings of Blacks and ratings of managers
      was nonsignificant (r' = .17). Managers were perceived to possess characteristics
      more commonly ascribed to Whites than to African Americans.

PMID- 9517316
TI  - Age, relationship, and touch initiation.
AB  - Gender asymmetry in touch in U.S. populations is related to the age of the
      participants in some studies and to the relationships between the participants in
      others. In the present study, researchers observed dyads in public settings in
      the United States frequented by couples and recorded the occurrence of touch, the
      touch initiator, and the body areas touched. The researchers then approached the
      couples and asked them to complete questionnaires indicating their ages, their
      relationship, and their level of agreement on major issues. Age and relationship
      were predictive of the gender of touch initiators. Although levels of agreement
      were less predictive of touch initiation, the women indicated higher levels of
      agreement than the men did. The results were generally consistent with a model of
      sex differences in reproductive strategies.

PMID- 9517317
TI  - Gender, social context, and backchannel responses.

PMID- 9517318
TI  - Self and others' perceptions of "crass materialism".

PMID- 9517319
TI  - Dimensionality of the Job-Related Tension Index: factor stability between two
      samples of women in the U.S. public sector.

PMID- 9517320
TI  - Inorganic aerosols and their role in catalyzing sulfuric acid production in
      furnaces.
AB  - Submicrometer ash and sulfur oxides are important pollutants formed during
      pulverized coal combustion. The submicrometer ash contains known catalysts for
      sulfur dioxide oxidation as well as alkaline species that will react with sulfur
      oxides. This work was an investigation to determine if submicrometer ash-sulfur
      oxide interactions can have a significant impact on the fate of sulfur. The
      submicrometer-ash-sulfur oxide interaction studies were carried out using
      submicrometer ash of controlled composition generated from the combustion of
      synthetic chars. The submicrometer ash was either exposed to SO2 in the
      combustion chamber or immobilized on a quartz-fiber filter for later exposure to
      SO2. Submicrometer-ash catalysis of SO2 oxidation was found to contribute
      significantly to the SO3 formed in the convective passes of a utility boiler,
      depending on the coal, combustion conditions, and temperature profile in the
      convective section. The calcium within the freshly formed submicrometer ash
      appears to sulfate more rapidly than would be predicted from rates published in
      the literature and is expected to sulfate completely in the convective section of
      a utility boiler.

PMID- 9517321
TI  - Control of toxic metal emissions from combustors using sorbents: a review.
AB  - This paper constitutes a review of the control of toxic metal emissions using
      sorbents. The objective of sorbent-injection methods is to effectively capture
      the metal species (preferably transform it to an environmentally benign form) and
      to suppress the fraction in the submicrometer mode. The design of an effective
      sorbent-injection methodology thus requires an understanding of the fate of the
      metallic species and its transformation pathways (transfer to the gas phase,
      subsequent chemistry at high temperatures, and aerosol formation and growth
      dynamics) in the combustor. Several different sorbent methodologies used for
      metals capture are discussed, and a mechanistic description is provided. The need
      for further experimentation and pilot scale testing is also emphasized.

PMID- 9517322
TI  - Revised hydrolysis constants for thallium(I) and thallium(III) and the
      environmental implications.
AB  - The hydrolysis constants for Tl(I) and Tl(III) have been determined by combining
      potentiometric measurement with the PKAS computer program. The log hydrolysis
      constants (Khi) for Tl(I)(OH)i-1i + H2O<==>Tl(I) (OH)i1-i + H+ have been
      determined to be -11.7, and those for Tl(III)(OH)i-1(4-i) + H2O<==>Tl(III)(OH)i3
      i + H+ are -2.69, -6.36, -7.42, and -8.78, respectively. The corresponding
      stepwise association constant for monovalent thallium is 10(2.3) for Tl(OH)aq,
      and those for trivalent thallium are 10(11.31) for Tl(OH)2+, 10(7.64) for
      Tl(OH)2+, 10(6.58) for Tl(OH)3aq, and 10(5.22) for Tl(OH)4-. The solubility
      product (Ksp) for solid Tl(OH)3,Solid has been redetermined to be 10(-45.2),
      implying that it is one of the least soluble among metal hydroxides. Revised
      fields of predominance of Tl(I) and Tl(III) hydroxides in aquatic environment are
      described, and the importance of Tl(III)/Tl(I) redox couple in the cycling of
      thallium is discussed.

PMID- 9517323
TI  - Health impact of polychlorinated dibenzo-p-dioxins: a critical review.
AB  - Polychlorinated dibenzo-p-dioxins (PCDDs), commonly known as dioxins, form as
      unwanted impurities in the manufacturing of chlorophenol and its derivatives-
      pulp and paper--and in the combustion of municipal, sewage-sludge, hospital, and
      hazardous waste. Combustion, in presence of a chlorine donor, seems to be a major
      source of these compounds. High levels of dioxins are also emitted from
      metallurgical industries including copper smelters, electric furnaces in steel
      mills, and wire reclamation incinerators. Trace levels are detectable in
      emissions from motor vehicles using leaded gasoline or diesel fuel, in forest
      fires, and in residential wood burning. Extremely persistent and widely
      distributed in the environment, PCDDs have been detected in all three primary and
      many secondary media. Releases into the air occur mainly from combustor
      emissions. Atmospheric dispersion, deposition, and subsequent accumulation in the
      food chain seem to be the major pathways of exposure to the general population.
      Residues of these chemicals have been detected in soil, sediment, fish, meat,
      cow's milk, human adipose tissue, and mothers' milk. In general, these chemicals
      have high lipophilicity. The elimination half-life of 2,3,7,8-tetrachlorodibenzo
      p-dioxin (TCDD) in humans is approximately 7-11 years. Very little human toxicity
      data from exposure to PCDDs are available. Health-effect data obtained from
      occupational settings in humans are based on exposure to chemicals contaminated
      with TCDD. It produces a spectrum of toxic effects in animals and is one of the
      most toxic chemicals known. Most of the toxicity data available on TCDD are from
      high-dose oral exposures to animals. Very few percutaneous and no inhalation
      exposure data are available in the literature. There is a wide range of
      difference in sensitivity to PCDD lethality in animals. The signs and symptoms of
      poisoning with chemicals contaminated with TCDD in humans are analogous to those
      observed in animals. Dioxin exposures to humans are associated with increased
      risk of severe skin lesions such as chloracne and hyperpigmentation, altered
      liver function and lipid metabolism, general weakness associated with drastic
      weight loss, changes in activities of various liver enzymes, depression of the
      immune system, and endocrine- and nervous-system abnormalities. It is a potent
      teratogenic and fetotoxic chemical in animals. A very potent promoter in rat
      liver carcinogenesis, TCDD also causes cancers of the liver and other organs in
      animals. Populations occupationally or accidentally exposed to chemicals
      contaminated with dioxin have increased incidences of soft-tissue sarcoma and non
      Hodgkin's lymphoma. No comprehensive studies have been conducted to determine any
      health impact to the general population from environmental exposure to PCDDs.
      This paper presents a brief review of relevant animal and human data for
      projecting any possible health effects from environmental exposures to PCDDs.

PMID- 9517324
TI  - Demand: shortage of dental hygiene services: an estimate of need.

PMID- 9517325
TI  - The new patient experience using intraoral video imaging.

PMID- 9517326
TI  - The art of crown preparation: a review of principles.
AB  - The following paper consists of a literature review related specifically to the
      biomechanical principles that determine the design and preparation of teeth:
      Retention and Resistance form. Magnitude of forces, geometry of tooth
      preparation, taper, stress concentration, the influence of luting agents and the
      clinical implication of these factors upon retention and resistance are presented
      and discussed from the point of view of several authors from the early 1900s
      until the present.

PMID- 9517327
TI  - Acute fluoride ingestion: recognition and management.
AB  - Occasionally, the Oral Health Division of the Indiana State Department of Health
      receives inquiries regarding diagnosis and treatment of acute fluoride ingestion.
      Because a wide variety of fluoride preparations are available in the dental
      setting and over the counter, excessive ingestion of fluoride can occur if these
      products are not used properly. The following article is meant to be a quick and
      easy guide in the recognition and management of instances of acute fluoride
      ingestion.

PMID- 9517328
TI  - Implant site preparation: a key to prosthetic success.
AB  - Implant site preparation allows the surgeon to place implant fixtures in the
      optimum position that is dictated by the final restoration. Armed with procedures
      to augment implant sites, the surgeon can enhance prosthetic success.

PMID- 9517329
TI  - Practical implant dentistry--the mandibular removable overdenture prosthesis.
AB  - The fully edentulous mandible presents functional, esthetic, and psychological
      challenges for the patient and the dentist. The mandibular overdenture supported
      by endosseous implants can provide a superior treatment modality, overcoming many
      of the difficulties inherent in the conventional denture. Advantages cited are
      increased denture retention, improved chewing efficiency, maintenance of bone
      height, replacement of lost anatomy, increased denture stability, reduction of
      soft tissue coverage and extension of the prosthesis, and easy access for hygiene
      maintenance. The major disadvantage rests with the patient's intolerance of a
      removable prosthetic design.

PMID- 9517330
TI  - Maintenance and treatment of the ailing and failing implant.
AB  - Due to the pathologic nature of oral bacteria, the partially edentulous implant
      patient is at a greater risk than the fully edentulous. Peri-implantitis and/or
      retrograde peri-implantitis can result in ultimate loss of the implant fixture.
      It is important that the implant dentist understand the difference between the
      ailing implant, the failing implant, and the failed implant. This article
      discusses the pathologic diseases that affect dental implants and how to treat
      the "infected" implant (degranulation and detoxification) for titanium and
      hydroxylapatite-coated implants. Implant maintenance, including hand or motorized
      brushes, flosses, and oral rinses (chlorhexidine, 0.2%) will also be presented.

PMID- 9517331
TI  - Embezzlement steals more than money.

PMID- 9517332
TI  - Safeguards help avoid embezzlement.

PMID- 9517334
TI  - Dental Health Center 2000.
AB  - The Dental Health Center concept is proposed as a method to maintain control of
      the dental delivery system while delegating the dentist's managerial and
      supervisory responsibilities to well-trained business executives. The Center
      would be a uniquely designed facility that operates 12 hours per day, 6 days a
      week for 50 weeks of the year. The participating dentists relocate their
      practices to the facility at a practice purchase price determined by the dentist,
      paid half in cash and half in center stock. In return, the dentists agree to
      produce that practice purchase price annually; in turn, they receive 45 percent
      of their monthly collected dental service fees and have access to all the
      services of the Center.

PMID- 9517333
TI  - Diagnosis and treatment planning for implant dentistry.
AB  - Dental implants are well-established in dentistry and allow the restorative
      dentist to offer patients the best that dentistry has to offer. Through
      examination, radiographs, and study models, the restorative dentist and implant
      surgeon can develop a treatment plan. Comprehensive diagnosis and treatment
      planning involve much more than a clinical exam--they require an investigation
      involving past, present and future dental therapy.

PMID- 9517335
TI  - 1995 Financial Survey--what does it mean to me?

PMID- 9517336
TI  - Practitioner and student latex exposure and allergy.
AB  - Greater application of universal precautions has increased practitioner exposure
      to chemicals present in personal protective equipment. Of prime concern is the
      latex present in examination and surgical gloves. A survey concerning latex
      exposure, allergies, and handwashing was administered to three advanced classes
      of dental students and was sent to 300 private practitioners in Central Indiana.
      Results indicate that adverse skin reactions to latex start while in dental
      school. Problems due to latex gloves were reported by 18.6 percent of the
      students. Student handwashing materials and methods were adequate, except for
      inadequate washing time. Adverse skin reactions were reported by 24.1 percent of
      practitioners wearing latex gloves. Two handwashing problems were noted-
      inadequate washing time and the common use of water instead of an antimicrobial
      soap after glove removal. Both students and practitioners reported relatively
      high levels of personal and family histories of allergy to a variety of sources.

PMID- 9517337
TI  - The use of sealants by Indiana dentists.

PMID- 9517338
TI  - Clinical comparison of magnetic resonance imaging and nuclear emission imaging in
      cervical-facial trauma patients.
AB  - This retrospective study examined 20 consecutively treated trauma patients who
      reported a chief complaint of earache or trauma preauricular pain. These
      individuals were examined with magnetic resonance imaging (MRI), emission study
      using single photon emission, computerized tomography, and joints auscultation
      using Doppler sound magnification. There are no statistically significant
      correlations between clinical findings and imaging studies in trauma patients
      with complaints of earaches and preauricular pain.

PMID- 9517339
TI  - Sterilization of slide sheath anesthetic injection systems placed within sharps
      containers.
AB  - The purpose of this study was to evaluate the effect that two steam autoclaves
      and an unsaturated chemical vapor sterilizer had on killing bacterial endospores
      present on commercial spore strips or applied to sterile anesthetic injection
      systems placed within sharps containers. Three types of sterilizers were used: a
      gravity steam autoclave, a high vacuum steam autoclave and an unsaturated
      chemical vapor sterilizer. The microbial challenge for the sterilizers were
      Bacillus stearothermophilus spores present on commercial spore strips or drawn
      into and applied onto sliding sheath anesthetic injection systems with anesthetic
      carpules attached. Spore-soiled items were placed into the middle of sharps
      containers three-quarters-filled with representative clinical waste and
      sterilized. If, after culturing, sterilization of all test items in a group was
      not achieved, additional sterilization time was applied. Spore strips were killed
      within a single cycle of each sterilizer. Spore-soiled injection systems and
      carpules could not be routinely sterilized in the gravity steam autoclave or
      unsaturated chemical vapor sterilizers, even after three consecutive
      sterilization cycles. These items, however, were sterilized by exposure to a
      single-treatment cycle in a high-vacuum steam autoclave. Results indicate that
      routine sterilization of spore contaminated anesthetic carpules or injection
      systems could not be accomplished in a reasonable amount of time using
      sterilizers commonly found in dental offices.

PMID- 9517341
TI  - Preliminary steps to computerization.
AB  - Selecting a computer system for a dental office is a complicated process and the
      author recommends that this be preceded by a careful practice analysis. Examples
      of the practicality of computerization are typified in several examples and many
      common pre-purchase suggestions and guidelines are provided. The need for staff
      involvement and adequate product review prior to purchase is discussed.

PMID- 9517340
TI  - Awareness of child abuse: a dental responsibility.
AB  - Although Indiana dentists are generally knowledgeable on the topic of child abuse
      and neglect, they need to be aware of their responsibilities as health care
      providers to identify and report child abuse and neglect. This is especially true
      when the abuse and neglect are identified in their patients. This article gives
      information on the types of abuse and neglect that are most commonly seen by
      dentists, indicators that should be "red flags" that abuse could be occurring and
      most importantly, how to report abuse.

PMID- 9517342
TI  - Computer software selection.
AB  - For many dental offices, good practice management software can offer significant
      benefits. A knowledge of available features, practice needs, and proper vendor
      selection are vital to initial and extended product satisfaction. This article
      discusses many available software features, their practicality, and proposes
      vendor demonstration and support obligations. Current legal issues, hidden costs,
      and data backup are presented as they pertain to the software selection process.

PMID- 9517343
TI  - Computer hardware selection.
AB  - After a suitable practice management software package has been selected, computer
      hardware will need to be purchased. Selection of the system hardware is dependent
      upon the requirements of the software to be used. The major hardware options as
      they pertain to practical use are addressed. Measures to improve reliability and
      service considerations are also discussed.

PMID- 9517344
TI  - Wastewater management: amalgam and silver--a critical issue.

PMID- 9517345
TI  - The prevalence of periodontal abscess.
AB  - The records of 5,467 periodontal patients in a military practice were reviewed
      for ADA case type 3 or 4, resulting in 203 patients (3.71 percent) in the two
      categories. These records were then examined for 1) sex of the patient; 2)
      occurrence of a periodontal abscess; 3) whether or not the patient was in active
      periodontal treatment at the time of the abscess; and 4) which tooth or teeth
      were involved. Periodontal treatment was shown to greatly reduce the incidence of
      periodontal abscesses among case type 3 patients. ADA case type 4 patients were
      much more likely to develop an abscess than case type 3 patients, and treatment
      had no effect on the rate of abscess formation in these patients. In those
      patients who developed an abscess while undergoing periodontal treatment, women
      showed a greater tendency toward abscess formation. Maxillary incisors and first
      premolars had the lowest rates of involvement.

PMID- 9517346
TI  - Tuberculosis: Indiana's status and implications for dental health care workers.

PMID- 9517348
TI  - Philosophical basis of outreach.

PMID- 9517347
TI  - Striving for professionalism: moral courage in dentistry. Senior essay, class of
      1994 Indiana University School of Dentistry.

PMID- 9517349
TI  - Dentistry's outreach to the needy. Who is responsible?

PMID- 9517350
TI  - Outreach in Indiana communities: more than meets the eye.

PMID- 9517351
TI  - Outreach at Indiana University School of Dentistry: giving back to the community.
AB  - This article describes the development, scope, and nature of numerous outreach
      programs initiated at I.U.S.D. It also addresses their intended impact at local,
      state, and national levels.

PMID- 9517352
TI  - Competency-based education at the Indiana University School of Dentistry.
AB  - This article discusses competency-based education at Indiana University School of
      Dentistry (IUSD). Competency-based education is not a new concept in health
      education, but is relatively new to dental education. The authors hope that this
      article will help Indiana dentists understand a process that will radically alter
      the way we teach dentistry at IUSD.

PMID- 9517354
TI  - Topical application of stannous fluoride inside of cavity preparations: a review
      of the literature.
AB  - A literature review concerning the topical application of fluorides inside of
      cavity preparations is presented. Several aspects, such as the type of compound
      to use, the time of application, and the advantages of the most recommended and
      used techniques, are discussed.

PMID- 9517353
TI  - Indiana dentists surveyed for effectiveness of biological testing of heat
      sterilization units.
AB  - The Indiana State Department of Health, Oral Health Services, randomly selected
      Indiana dentists to ascertain their compliance toward biological testing of heat
      sterilization units. Slightly more than 85 percent of the dentists surveyed were
      in compliance with the law regulating biological testing of heat sterilization
      units.

PMID- 9517355
TI  - Capturing the value of your practice on retirement.

PMID- 9517356
TI  - Abusing and neglecting kids.

PMID- 9517357
TI  - Child abuse--a dentist's responsibility?

PMID- 9517358
TI  - Child abuse: why should I report it?
AB  - In Indiana, dental professionals are mandated by law to report suspected child
      abuse and neglect to Child Protective Services (CPS) or the law enforcement
      agency in their county. The penalty for non-reporting is fine and/or jail. This
      article will give dental professionals information on child abuse injuries that
      can be identified in the dental office, how to talk to the child and family
      members regarding suspicions, and how to report those suspicions to your local
      CPS or law enforcement agency. Dental professionals will receive reassurance and
      encouragement from this article to report suspected cases of child abuse to CPS
      or law enforcement. The report is not meant to be punitive, but is intended to
      get the family connected to services to assist them, the child, and any other
      children they have or may have in the future, to avoid further abuse, and to
      attempt to break the cycle of abuse. To report suspicions of child abuse in
      Indiana, dial: 1-800-800-5556.

PMID- 9517359
TI  - A report on Indiana PANDA. Prevention of Abuse and Neglect through Dental
      Awareness.
AB  - Since originally surveying Indiana dentists' knowledge of child abuse and neglect
      in 1990, numerous efforts have been made to help dental professionals improve
      their ability to identify and report instances of abuse. This article explains
      the purpose for the 1995 follow-up survey and why dental professionals'
      assistance is needed to complete the surveys. A second survey is scheduled for
      distribution six months after the Prevention of Abuse and Neglect through Dental
      Awareness (PANDA) efforts have been implemented to determine if those efforts are
      far having an effect throughout Indiana.

PMID- 9517360
TI  - Clinical orthodontics in predoctoral education. Six years of experience at
      Indiana University.
AB  - Since 1990, clinical achievement in orthodontics has been a graduation
      requirement at Indiana University. To be certified for graduation, all dental
      students must treat at least one limited orthodontic problem and observe the
      retention of at least one previously treated, limited orthodontics patient.
      Although clinical orthodontics for adults appears to be a very successful
      addition to the predoctoral curriculum, the specific accreditation requirements
      that mandated it have been rescinded. However, the positive response of the
      students, apparent acceptance by the orthodontic community, and the national
      acclaim afforded the program indicate that a hands-on clinical experience in
      orthodontics is a positive addition to the predoctoral curriculum.

PMID- 9517361
TI  - Osteoporosis risk factors in female dental patients. A preliminary report.
AB  - Osteoporosis (OP) is a systemic condition that has dental implications. The
      purpose of this study was to compare OP risk among various dental specialty
      subpopulations at Indiana University School of Dentistry (IUSD). A survey was
      administered to 220 adult female dental patients assessing menstrual status and
      risk behaviors associated with low bone mass. The subjects' mean age was 48.2 +/-
      1.1 years (mean +/- SEM). Overall, 38% of the surveyed patients exhibited high
      risk for OP. The orthodontic subpopulation (a dentate group with routine
      developmental malocclusions) was the youngest group and contained the lowest
      percentage at high-risk (6%). Conversely, the complete denture subpopulation was
      the oldest and contained the highest percentage of patients at high risk (53%).
      Postmenopausal women who had inadequate hormone replacement therapy exhibited a
      strong negative correlation for number of teeth retained with increasing years
      postmenopause (r = 0.6). Patients in the implant therapy group (many of which had
      adjunctive orthodontic care) had a mean age similar to the complete denture
      group, but a much lower risk for OP. This appears to be due to the extensive
      counseling these patients receive prior to treatment. It is concluded that risk
      factor analysis and patient counseling may be effective measures for reducing the
      osteoporosis risk of dental patients.

PMID- 9517362
TI  - Adjunctive orthodontic therapy in adults over 50 years of age. Clinical
      management of compensated, partially edentulous malocclusion.
AB  - Increasing numbers of adults, with a wide range of compensated partially
      edentulous (CPE) malocclusions, could benefit from adjunctive orthodontic
      therapy. Because loss of teeth is a risk factor for osteoporosis (OP) and
      restoration of occlusion depends on a positive bone response, all subjects in a
      prospective clinical trial were screened for OP risk factors and other bone
      related metabolic problems. The sample consisted of 16 potential orthodontic
      patients (3 males, 13 females) over the age of 50. Based on risk factor analysis,
      six (44%, 1 male and 6 females) were referred for medical evaluation including
      bone mineral density (BMD) measurement. Ultimately, five osteopenic/osteoporotic
      patients, along with four patients reporting no significant osteoporotic risk
      factors, completed multidisciplinary treatment including adjunctive orthodontics.
      All were successfully treated to what was considered to be optimal esthetics and
      function with no substantial complications. It was concluded that patients over
      50 years of age of both sexes can be effectively treated orthodontically if they
      have a healthy periodontium, retain an adequate residual dentition, can be
      controlled medically, and are compliant with treatment recommendations. Overall,
      orthodontics was a readily accepted, cost-effective aspect of treatment that
      substantially improved the esthetics and function of patients with moderate to
      severe CPE malocclusion.

PMID- 9517363
TI  - Multidisciplinary management of congenital and acquired compensated
      malocclusions: diagnosis, etiology and treatment planning.
AB  - Restoration of optimal occlusal function, consistent with desirable esthetics and
      a favorable long-term prognosis, is the clinical goal for management of
      compensated malocclusions in partially edentulous patients. An appropriate
      diagnostic work-up includes a careful assessment of etiology, relative to both
      genetic and environmental factors. Esthetic and cost-effective restoration of
      occlusal function often requires adjunctive orthodontic therapy, integrated into
      a comprehensive treatment plan. Alignment of abutments, management of edentulous
      space and enhancement of soft tissue contours are important preprosthetic
      objectives. Osseointegrated dental implants provide occlusal stops to open the
      vertical dimension of occlusion and serve as rigid anchorage for three
      dimensional orthodontic alignment of the residual dentition. Carefully
      coordinated preprosthetic treatment to establish bilateral posterior occlusion
      (molars and/or implants) is an important goal for achieving a biomechanically
      optimized restoration of occlusion. Fundamental diagnostic and treatment planning
      procedures are reviewed for the multidisciplinary management of partially
      edentulous, compensated malocclusions. Determining the probable etiology of a
      malocclusion is an important prerequisite for formulating a treatment plan with a
      reasonable probability of success. Diagnostic considerations are presented and
      clinical examples of specific orthodontic methods are illustrated. To demonstrate
      the application of fundamental principles at the clinical level, a case report is
      presented with a diagnosis and treatment plan for a malocclusion with both
      genetic and functional implications.

PMID- 9517364
TI  - Health technology assessment--the role of the pharmaceutical panel.

PMID- 9517365
TI  - Antiretroviral therapy for patients with HIV disease.

PMID- 9517366
TI  - Characteristics of indirect pharmacodynamic models and applications to clinical
      drug responses.
AB  - This review describes four basic physiologic indirect pharmacodynamic response
      (IDR) models which have been proposed to characterize the pharmacodynamics of
      drugs that act by indirect mechanisms such as inhibition or stimulation of the
      production or dissipation of factors controlling the measured effect. The
      principles underlying IDR models and their response patterns are described. The
      applicability of these basic IDR models to characterize pharmacodynamic responses
      of diverse drugs such as inhibition of gastric acid secretion by nizatidine and
      stimulation of MX protein synthesis by interferon alpha-2a is demonstrated. A
      list of other uses of these models is provided. These models can be readily
      extended to accommodate additional complexities such as nonstationary or
      circadian baselines, equilibration delay, depletion or accumulation of a
      precursor pool, sigmoidicity, or other mechanisms. Indirect response models which
      have a logical mechanistic basis account for time-delays in many responses and
      are widely applicable in clinical pharmacology.

PMID- 9517367
TI  - A limited sampling method for the estimation of AUC and Cmax of carbamazepine and
      carbamazepine epoxide following a single and multiple dose of a sustained-release
      product.
AB  - AIMS: The objectives of this study are to develop a model to predict area under
      the curve (AUC) and maximum plasma concentration (Cmax) of carbamazepine (CBZ)
      and its active metabolite carbamazepine epoxide (CBZE) following single and
      multiple dose of CBZ using one or two samples in volunteers. METHODS: Limited
      sampling models (LSM) were developed for CBZ and CBZE following 200-800 mg single
      oral dose and 400-800 mg twice daily dose for 14 days of a sustained-release
      product (CBZ-SR) to estimate AUC and Cmax. The LSM was developed from a training
      data set of 15 subjects using one blood sample taken at 48 h following a single
      dose. The model was validated on 60 subjects who received different doses of CBZ.
      Following multiple dosing, the LSM was developed from a training data set of 10
      subjects using the steady state Cmin (plasma concentration obtained 5 min before
      the last CBZ-SR dose). RESULTS: The model provided good estimates of AUC and Cmax
      for CBZ and CBZE. The bias and the precision of the predicted AUC and Cmax for
      CBZ and CBZE were less than 10% and 15%, respectively. Similar results were
      obtained when CBZ was given as multiple dose. CONCLUSIONS: The method described
      here may be used to estimate AUC and Cmax for CBZ and CBZE without detailed
      pharmacokinetic studies following single or multiple dose of CBZ.

PMID- 9517368
TI  - Gut wall metabolism of verapamil in older people: effects of rifampicin-mediated
      enzyme induction.
AB  - AIMS: To investigate prehepatic metabolism of verapamil and its inducibility by
      rifampicin in older subjects. METHODS: Eight older subjects (67.1 +/- 1.2 years
      mean +/- s.d.) received racemic, unlabelled verapamil orally for 16 days (120 mg
      twice daily). Rifampicin (600 mg daily) was coadministered from day 5 to 16.
      Using stable isotope technology (i.e. intravenous coadministration of 10 mg
      deuterated verapamil) during verapamil steady-state without (day 4) and with
      rifampicin (day 16) bioavailability, prehepatic and hepatic extraction of
      verapamil were determined. The effects of verapamil on AV-conduction were
      measured by the maximum PR interval prolongation (%). RESULTS: Bioavailability of
      the cardiovascularly more active S-verapamil decreased from 14.2 +/- 4.3% on day
      4 to 0.6 +/- 0.5% on day 16 (P < 0.001). As a consequence, effects of orally
      administered verapamil on the AV-conduction were nearly abolished (14.4 +/- 9.4%
      vs 2.7 +/- 2.6%, P < 0.01). This could be attributed to a considerable increase
      of prehepatic extraction during treatment with rifampicin (41.7 +/- 22.1% vs 91.6
      +/- 6.6%, P < 0.01) and to a minor extent to induction of hepatic metabolism
      (73.7 +/- 9.4% vs 91.6 +/- 5.3%, P < 0.01). CONCLUSIONS: Prehepatic metabolism of
      verapamil occurred in the group of older people investigated. Induction of gut
      wall metabolism most likely was the major reason for the loss of verapamil effect
      during treatment with rifampicin in this group of older subjects.

PMID- 9517369
TI  - Non-linear fluvoxamine disposition.
AB  - AIMS: To study the pharmacokinetics of fluvoxamine when given in increasing doses
      to healthy volunteers. METHODS: Ten healthy, non-smoking men were given
      maintenance treatment with fluvoxamine for 4 weeks. Eight subjects were CYP2D6
      extensive metabolisers (EMs) and two were CYP2D6 poor metabolisers (PMs). As a
      measure of the CYP1A2 phenotype, the paraxanthine/caffeine ratio in saliva after
      intake of caffeine was studied. The fluvoxamine doses given were 25 mg day(-1)
      the first week, 50 mg day(-1) the second week, 100 mg day(-1) the third week and
      200 mg day(-1) the fourth week, divided in two daily doses. On the seventh day
      every week, serum concentrations of fluvoxamine were followed for a dose interval
      of 12 h. After discontinuation of treatment, fluvoxamine concentrations were
      followed for 1 week. RESULTS: For each of the three two-fold increases in given
      dose, the mean AUC increased 3.25-fold, 3.17-fold and 3.14-fold, respectively (P
      < 0.0001), indicating a decrease in oral clearance with increasing dose. The
      elimination half-life based upon the serum concentrations 12-48 h after
      discontinuation of fluvoxamine was 32.1 +/- 11.0 h whereas the half-life based
      upon the concentrations 3-7 days after discontinuation was significantly shorter,
      15.8 +/- 4.2h (means +/- s.d.; P < 0.001). There were no significant correlations
      between the CYP1A2 phenotype and fluvoxamine AUCs at different doses (r = -0.56;
      P = 0.095 for the correlation between the paraxanthine/caffeine ratio in saliva
      and fluvoxamine AUC at a dose of 50 mg day[-1]). The two CYP2D6 PMs had AUC
      values in the same range as the EMs. CONCLUSIONS: The present study conclusively
      demonstrates that fluvoxamine exhibits non-linear kinetics within the therapeutic
      dose interval. The reason for non-linearity is not Michaelis-Menten saturation
      kinetics of a single metabolic pathway, but rather a complex involvement of
      multiple parallel pathways.

PMID- 9517370
TI  - Lipoprotein composition and oxidative modification during therapy with
      gemfibrozil and lovastatin in patients with combined hyperlipidaemia.
AB  - AIM: To evaluate the resistance to oxidation of human lipoproteins after
      hypolipidaemic therapy. METHODS: VLDL and LDL samples were obtained from patients
      with Familial Combined Hyperlipidaemia included in a randomized, double-blind,
      cross-over study, with 8 weeks of active treatment (gemfibrozil, 600 mg twice
      daily, or lovastatin, 40 mg daily) and a 4-week wash-out period. Oxidation
      related analytes after Cu-induced oxidation of VLDL and LDL have been
      investigated. Further, in order to relate possible changes in oxidative behaviour
      to lipoprotein composition, the proportion of the lipid species transported by
      lipoproteins (triglycerides, phospholipids, and cholesteryl esters), the molar
      composition of fatty acids for each lipoprotein lipid, and the content of
      antioxidant vitamins in plasma (vitamin C) and lipoproteins (vitamin E) have been
      studied. RESULTS: Both drugs reduced the plasma concentration of apo-B
      lipoproteins (-23% gemfibrozil, -26% lovastatin), but whereas lovastatin affected
      mainly LDL-cholesterol (-30%), gemfibrozil reduced triglycerides (-49%) and VLDL
      cholesterol (-48%). Lovastatin treatment had no effect on the lipid and protein
      composition, the fatty acid profile, or the vitamin E content of either VLDL or
      LDL; likewise, lipoprotein oxidation markers (Cu-induced conjugated dienes,
      thiobarbituric acid reactive substances formation, and lysine residues) were
      similar before and after lovastatin treatment. Gemfibrozil therapy also had no
      effect on lipoprotein oxidation; nevertheless, it consistently: a) decreased the
      proportion of LDL-triglycerides (-32%), and b) increased the proportion (molar%)
      of 18:3 n-6 in VLDL triglycerides (+140%), phospholipids (+363%) and cholesteryl
      esters (+53%). CONCLUSIONS: Based on these results, lovastatin and gemfibrozil do
      not adversely affect lipoprotein oxidation in patients with mixed dyslipidaemia.
      In the case of gemfibrozil, this occurs in spite of an increased proportion of
      some polyunsaturated fatty acids in VLDL. In the context of a fixed dietary
      intake, such modifications suggest that the drug influences liver enzyme
      activities involved in fatty acid chain synthesis (elongases and desaturases).

PMID- 9517371
TI  - Comparison of the effects of nadolol and bisoprolol on noradrenaline-evoked
      venoconstriction in man in vivo.
AB  - AIMS: In an attempt to explore the possible involvement of venodilator beta
      adrenoceptors in the constrictor response of the human dorsal hand vein to
      noradrenaline, we examined the ability of nadolol, a non-selective beta1/beta2
      adrenoceptor antagonist, and bisoprolol a selective beta1-adrenoceptor
      antagonist, to potentiate the response. METHODS: Twelve healthy male volunteers
      participated in three weekly sessions. In each session nadolol (40 mg),
      bisoprolol (5 mg) or placebo was ingested, and (-) noradrenaline acid tartrate
      (0.33-33.33 ng min ) was infused locally into the dorsal hand vein 2 h after the
      ingestion of the drugs. Changes in vein diameter were monitored with the dorsal
      hand vein compliance technique. Subjects were allocated to treatments and
      sessions according to a double-blind balanced cross-over design. Systolic and
      diastolic blood pressure, and heart rate were also measured. RESULTS:
      Noradrenaline produced dose-dependent venoconstriction which was antagonized by
      bisoprolol but remained unaffected by nadolol (ANOVA with repeated measures:
      F(2,22) = 5.07, P < 0.025; Dunnett's test: placebo vs nadolol; t = 0.35, df = 22,
      k = 3, NS; placebo vs bisoprolol; t = 2.83, df = 22, k = 3, P < 0.01). Mean (+/-
      s.e. mean) logED50s (ng min[-1]) were 0.44 +/- 0.15 (placebo), 0.73 +/- 0.11
      (bisoprolol) and 0.50 +/- 0.21 (nadolol); mean (95% CI) differences were 0.29 (
      0.005, 0.58) for placebo vs bisoprolol and 0.06 (-0.35, 0.46) for placebo vs
      nadolol. Both active drugs significantly (compared with placebo, P < 0.05)
      decreased (mean change from pretreatment +/- s.e. mean) heart rate (bisoprolol 
      16.08 +/- 2.01; nadolol -11.67 +/- 2.06) and systolic blood pressure (bisoprolol 
      15.0 +/- 0.80; nadolol -9.47 +/- 0.18). CONCLUSIONS: The failure of nadolol and
      bisoprolol to potentiate noradrenaline-evoked venoconstriction argues against the
      involvement of masked venodilator beta-adrenoceptors in the response. The
      mechanism underlying the antagonism of noradrenaline-evoked venoconstriction by
      bisoprolol remains to be elucidated.

PMID- 9517373
TI  - The reproducibility of symptoms during a submaximal exercise test in chronic
      heart failure.
AB  - AIMS: The aim of this study was to evaluate the use of a submaximal test with a
      symptom limited endpoint and to measure the reproducibility of symptoms in
      patients with CHF. METHODS: Ten patients with chronic heart failure were studied.
      Based on two maximal treadmill tests an individual protocol using a constant work
      rate at a submaximal intensity was derived. The projected maximum treadmill time
      for the constant workrate was between 8 and 17 min. Tests were carried out 1, 2,
      4 and 6 weeks after the maximum tests. Every 2.5 min during the submaximal test
      patients recorded their symptoms of breathlessness and fatigue using computer
      automated visual analogue (VAS) and Borg CR10 scales. The measure of
      reproducibility used was the proportion of total variability explained by the
      between subject variability. RESULTS: Using the VAS scale, general fatigue was
      reasonably reproducible ranging from 77-86%. For VAS breathlessness
      reproducibility ranged from 66% to 83%. Reproducibility for breathlessness and
      fatigue for the Borg CR10 scale was much lower than the VAS scale.
      Reproducibility for the treadmill times was 51% but increased to 76% if one test
      of one subject was excluded. CONCLUSIONS: The use of the VAS during submaximal
      exercise offers a useful means of evaluating symptoms in CHF and potentially
      their response to treatment. These findings show that individual submaximal
      protocols can be easily prescribed for CHF patients. Using such an approach,
      clinically desirable tests lasting around 12 min can be developed. These tests
      are reasonably reproducible and may provide a useful means of assessing patient
      disability and the impact of treatment.

PMID- 9517372
TI  - The dose-response effects of terbutaline on the variability, approximate entropy
      and fractal dimension of heart rate and blood pressure.
AB  - AIMS: To study the dose-response effects of intravenous terbutaline on the
      cardiovascular and respiratory autonomic nervous regulation. METHODS: The study
      followed a randomized, placebo-controlled crossover design in six healthy adult
      volunteers. The terbutaline dose ranged from 10 to 30 microg min(-1) We
      continuously measured electrocardiogram, finger systolic arterial pressure (SAP)
      and flow-volume spirometry in supine and upright positions at baseline and during
      3 h drug infusion. The periodic variability components of R-R intervals (time
      between successive heart beats) and SAP in relation to respiration were assessed
      using spectral analysis techniques. The regularity of the time series was
      assessed by approximate entropy (ApEn) and the convolutedness by fractal
      dimension (FD). RESULTS: Terbutaline dose-dependently decreased total variability
      of R-R intervals, low frequency (LF) variability of R-R intervals (10 s waves),
      high frequency (HF) variability of R-R intervals (respiratory variability), total
      variability of SAP, HF variability of SAP, baroreflex sensitivity, plasma
      potassium concentration, approximate entropy of R-R interval and of SAP as well
      as fractal dimension of R-R interval. Terbutaline dose-dependently increased
      heart rate, LF/HF ratios of R-R intervals and of SAP, LF variability of SAP,
      minute ventilation and plasma terbutaline concentration. CONCLUSIONS: Terbutaline
      infusion decreases parasympathetic cardiovascular reactivity, baroreflex
      sensitivity, dimensionality of heart rate and plasma potassium concentration; it
      increases sympathetic dominance in cardiovascular autonomic balance, minute
      ventilation, and the regularity of heart rate and blood pressure time series.

PMID- 9517374
TI  - Molecular effects of sulphonylurea agents in circulating lymphocytes of patients
      with non-insulin-dependent diabetes mellitus.
AB  - AIMS: In circulating lymphocytes of NIDDM patients pyruvate dehydrogenase (PDH),
      the major determinant in glucose consumption through oxidative pathways, is
      poorly active. The aim of this study is to examine whether sulphonylurea drug
      treatment revives PDH activity in circulating lymphocytes from NIDDM patients.
      METHODS: Twenty normal-weight individuals with NIDDM were enrolled in this study.
      They had maintained their glycaemic levels close to normal by means of a
      restricted diet that had no longer been successful in the proceeding 2 months.
      The treatment protocol consisted in 160 mg gliclazide daily for 5 weeks. Twenty
      healthy subjects, matched for age, body mass index and gender, were enrolled as a
      control group. Patients, before and after treatment, as well as controls were
      tested for PDH activity in their circulating lymphocytes. Nine other untreated
      patients and nine healthy subjects, with the above mentioned characteristics,
      were recruited for the assay of PDH activity in their circulating lymphocytes
      before and after exposure, in vitro, to gliclazide, to insulin, and to gliclazide
      and insulin in combination. RESULTS: In gliclazide-treated NIDDM patients, PDH
      activity in circulating lymphocytes recovered. In vitro, in circulating
      lymphocytes of untreated patients and controls insulin at 5 microU ml(-1) was
      ineffective and highly effective, respectively, in raising enzyme activity;
      gliclazide at 10 ng ml(-1) was ineffective on PDH in both groups, but in
      combination with insulin at 5 microU ml(-1) in both groups PDH was as active as
      in cells of controls exposed to insulin only. In cells of controls, gliclazide
      alone at 25-50 ng ml(-1) caused enzyme activation, whereas above 50 ng ml(-1) it
      caused inhibition; in cells of patients below 50 ng ml(-1) it had no effects, but
      at 50 ng ml(-1) and above raised enzyme activity to the basal level of controls.
      CONCLUSIONS: This study suggests that free gliclazide concentrations determine
      recovery of PDH activity in circulating lymphocytes of treated patients through
      drug-mediated enhanced insulin control over PDH or through the drug alone.

PMID- 9517376
TI  - The inhibitory effect of propranolol on ATP-sensitive potassium channels in
      neonatal rat heart.
AB  - 1. Whole cell and single channel recordings of ATP-sensitive K+ current
      (I(K,ATP)) were carried out in ventricular myocytes isolated from neonatal rat
      hearts. 2. (+/-)-Propranolol, a commonly used beta-blocker, inhibited the whole
      cell I(K,ATP) in a concentration-dependent manner with a half-maximal
      concentration (IC50) of 6.7 +/- 1.4 microM, whereas it blocked the inward
      rectifier K+ current (I(K,I)) only at much higher concentrations (IC50 = 102.4 +/
      20.2 microM). The inhibition was time- and voltage-independent. 3. In the
      outside-out patch configuration, (+/-)-propranolol inhibited I(K,ATP) (IC50 = 9.8
      +/- 2.9 microM) by decreasing the open probability of the channel without
      inducing additional noise in the open-channel current or a decrease of single
      channel conductance. The single channel current of I(K,I) was also blocked by (+/
      )-propranolol in the same way as I(K,ATP). 4. (+)-Propranolol, an optic isomer
      having no beta-blocking effect, inhibited I(K,ATP) (IC50 = 5.8 +/- 1.0 microM),
      whilst atenolol, a selective beta1-blocker had no effect. Neither GDPbetaS (1 mM)
      nor GTPgammaS (200 microM) included in the pipette solution modulated the
      inhibitory effect of (+/-)-propranolol. 5. We concluded that the inhibitory
      effect of (+/-)-propranolol was not via the beta-adrenergic signal transduction
      pathway, but by direct inhibition of I(K,ATP) channels.

PMID- 9517377
TI  - Ipriflavone as an inhibitor of human cytochrome P450 enzymes.
AB  - 1. Reduction of theophylline metabolism and elimination were observed in a
      theophylline-treated patient during ipriflavone administration. After withdrawal
      of ipriflavone, the serum theophylline level decreased to an extent similar to
      that found before administration of ipriflavone. The effects of ipriflavone and
      its major metabolites 7-hydroxy-isoflavone and 7-(1-carboxy-ethoxy)-isoflavone on
      cytochrome P450 activities were studied in vitro in human liver microsomes from
      three donors. 2. Ipriflavone and 7-hydroxy-isoflavone competitively inhibited
      phenacetin O-deethylase and tolbutamide hydroxylase activity. The parent compound
      and its dealkylated metabolite were strong inhibitors exhibiting Ki values around
      10-20 microM, while 7-(1-carboxy-ethoxy)-isoflavone had no effect on the
      cytochrome P450 activities investigated. 7-Hydroxy-isoflavone is the only one
      that influenced nifedipine oxidase activity. It competitively inhibited this
      activity with a Ki value of 129.5 microM. 3. The steady state concentrations of
      ipriflavone and 7-hydroxy-isoflavone in plasma of patients receiving 3 x 200 mg
      daily doses of ipriflavone for 48 weeks were found to be 0.33 +/- 0.32 microM and
      1.44 +/- 0.77 microM, respectively. 4. The results indicate that the decrease in
      theophylline metabolism observed in a patient treated with ipriflavone may be due
      to a competitive interaction of ipriflavone or its metabolite, 7-hydroxy
      isoflavone with CYP1A2. On the other hand, our in vitro findings predict some
      more interaction with CYP2C9.

PMID- 9517375
TI  - Frequency and cost of serious adverse drug reactions in a department of general
      medicine.
AB  - AIMS: To assess the frequency and cost of drug reactions causing or prolonging
      hospitalization. METHODS: All patients admitted to an internal medicine ward over
      6 months were evaluated to identify serious adverse reactions. The number of drug
      classes on admission or at the time of the adverse drug reaction (ADR) was
      counted. Excess ADR-related hospital stay was computed using a) raw excess
      duration of hospital stay, b) correction of duration of hospital stay by age,
      sex, and number of drug classes, and c) estimation by investigator of excess
      hospital stay. RESULTS: Three hundred and twenty-nine patients were evaluated:
      212 male, 117 female, mean age 57.2 (males: 52.2, females: 66.2 (P < 0.05)),
      range 17-95 years. They stayed a total of 3720 hospital days (mean stay 11.3
      days). 298 had no ADR (mean age 55.8, taking a mean of 2.7 drug classes, 10.7
      days hospital stay); 31 had ADRs: in 10, the ADR caused admission in patients
      with a mean age of 84 (P < 0.01 vs the two other groups), taking 6.3 drug
      classes, who stayed a mean of 15.1 days; 21 occurred in hospital in patients with
      a mean age of 63.6, taking 4.2 drug classes (P < 0.01), who stayed a mean of 19.2
      days (P < 0.01 vs patients without ADRs). In four the ADR was fatal (13% of ADRs,
      40% of deaths). Raw ADR-related excess hospital stay was 318 days (8.6% of all
      hospital days), after multivariate correction 282 days (7.6% of all hospital
      days), and with investigator estimation 197 days (5.3% of all hospital days).
      Point prevalence of ADRs at admission was 3%, incidence rate in hospital was
      5.6/1000 patient-days. CONCLUSIONS: 3% of the admissions were related to ADRs. In
      addition, 6.6% of hospitalized patients had significant ADRs. Between 5 and 9% of
      hospital costs were related to ADRs. In 24 of the 31 patients with ADRs (77%),
      these were related to the pharmacological properties of the involved drugs, and
      may possibly have been avoidable.

PMID- 9517378
TI  - Effect of trimetazidine and verapamil on the cardiomyopathic hamster myosin
      phenotype.
AB  - 1. In this study we investigated whether long-term trimetazidine (anti-ischaemic
      drug) therapy alters the ventricular myosin heavy chain (MHC) isoform composition
      in a model of cardiomyopathy. 2. MHC isoforms were analysed in the native state
      by electrophoresis in a pyrophosphate buffer. Myosin isoform patterns were
      studied in cardiac muscle from cardiomyopathic hamsters (CMH) of the BIO 14:6
      strain during the time course of the disease and compared with those of healthy
      golden hamsters (F1B). The correlation between myosin profile and Ca2+-activated
      ATPase activity was determined from 220 days. 3. At the stage of insufficiency
      (350 days), CMH presented the most abnormal phenotype with 53% V1-24% V3 compared
      to 79% V1-7% V3 (P<0.001), in F1B. Trimetazidine was administered to
      cardiomyopathic hamsters from the early stage of active disease (30 days) to the
      congestive stages (220-350 days). Within 65 days, trimetazidine treatment, in CMH
      and F1B, reduced V1 to a low level (53% and 62%, respectively), which remained
      constant throughout the treatment. This level was similar to that in 220 and 350
      days-old untreated-CMH. In sharp contrast, a standard calcium blocker, verapamil,
      administered to CMH in the same conditions resulted in a higher V1 (about 70%)
      and higher global myosin ATPase activity from 220 days. 4. Previous results in
      terms of hypertrophy and survival, compared to these results, suggest that
      verapamil and trimetazidine treatments reveal a dissociation between ventricular
      hypertrophy and isomyosin distribution. In addition, the shift in favour of V3
      may not necessarily be an aggravating factor of the disease but an adaptative
      compensatory event.

PMID- 9517379
TI  - Mediators and mechanisms of relaxation in rabbit urethral smooth muscle.
AB  - 1. Electrophysiological and mechanical experiments were performed to investigate
      whether the nitric oxide (NO)-mediated relaxation of rabbit urethral smooth
      muscle is associated with a hyperpolarization of the membrane potential. In
      addition, a possible role for vasoactive intestinal peptide (VIP) and carbon
      monoxide (CO) as relaxant agents in rabbit urethra was investigated. 2.
      Immunohistochemical experiments were performed to characterize the NO-synthase
      (NOS) and VIP innervation. Possible target cells for NO were studied by using
      antisera against cyclic GMP. The cyclic GMP-immunoreactivity was investigated on
      tissues pretreated with 1 mM IBMX, 0.1 mM zaprinast and 1 mM sodium
      nitroprusside. 3. Intracellular recordings of the membrane potential in the
      circular smooth muscle layer revealed two types of spontaneous depolarizations,
      slow waves with a duration of 3-4 s and an amplitude of 30-40 mV, and faster (0.5
      1 s), more irregular depolarizations with an amplitude of 5-15 mV. The resting
      membrane potential was 39 +/- 1 mV (n = 12). Application of NO (30 microM), CO
      (30 microM) or VIP (1 microM) did not change the resting membrane potential. 4.
      Both NO (1-100 microM) and VIP (1 nM-1 microM) produced concentration-dependent
      relaxations amounting to 87 +/- 4% and 97 +/- 2% (n = 6), respectively. The
      relaxant effect of CO (1-30 microM) amounted to 27 +/- 4% (n = 5) at the highest
      concentration used. 5. Immunohistochemical experiments revealed a rich supply of
      NOS-immunoreactive nerve fibres in the smooth muscle layers. Numerous spinous
      cyclic GMP-immunoreactive cells were found interspersed between the smooth muscle
      bundles, mainly localized in the outer layer. These cells had long processes
      forming a network surrounding the smooth muscle bundles. VIP-immunoreactivity was
      sparse in comparison to NOS-immunoreactive nerves. 6. The rich supply of NOS
      immunoreactive nerve fibres supports the view that NO is an important NANC
      mediator in the rabbit urethra. In contrast to several other tissues, the
      relaxant effect of NO in the rabbit urethra does not seem to be mediated by
      hyperpolarization. The network of cyclic GMP-immunoreactive cells may constitute
      target cells for NO, but their function remains to be established.

PMID- 9517381
TI  - Effects of rolipram on cyclic AMP levels in alveolar macrophages and
      lipopolysaccharide-induced inflammation in mouse lung.
AB  - 1. Our previous work demonstrated that bacterial lipopolysaccharide (LPS),
      administered by aerosol, induced tumour necrosis factor (TNF-alpha) synthesis
      leading to the infiltration of neutrophils into mice lungs. The treatment of
      animals with prostaglandin E2 or dibutyryl cyclic AMP impaired both processes. In
      this study, the target cell for LPS and the modulation by cyclic AMP of TNF-alpha
      production and neutrophil recruitment were investigated. 2. One hour after
      inhalation of 2 ml of 0.3 mg ml(-1) LPS, TNF-alpha levels measured by an ELISA
      method increased in the bronchoalveolar lavage fluid (BALF) of BALB/c mice,
      reaching a maximal level 3 h after inhalation. The immunocytochemistry assay
      demonstrated that 1 h after inhalation, 21.2% of alveolar macrophages collected
      in the BALF were immunopositive for TNF-alpha. 3. When mice were pretreated,
      i.p., with 20 mg kg(-1) rolipram, a selective inhibitor of phosphodiesterase type
      4, TNF-alpha levels in the BALF were significantly reduced and only 7.3% of
      alveolar macrophages were immunopositive for TNF-alpha. 4. Alveolar macrophages
      from rolipram-treated mice collected 30 min after inhalation of LPS had a
      significant increase in the intracellular concentrations of cyclic AMP. This was
      accompanied by a marked reduction of TNF-alpha levels in the BALF that were
      associated with a suppression of TNF-alpha mRNA expression. 5. Systemic treatment
      with 20 mg kg(-1) rolipram almost completely inhibited the LPS-induced neutrophil
      recruitment, whereas it did not significantly reduce the recruitment induced by
      rmTNF-alpha. 6. Our results indicate that alveolar macrophages may be the target
      cells for both the induction and control of the lung inflammatory response to
      LPS. They also suggest that systemic treatment with cyclic AMP-elevating agents
      may be useful to control local inflammation resulting from inhalation of
      bacterial endotoxin.

PMID- 9517380
TI  - Blockade of the development of morphine tolerance by U-50,488, an AVP antagonist
      or MK-801 in the rat hippocampal slice.
AB  - 1. In this study, we investigated the effects of different drugs (a kappa-opioid
      receptor agonist U-50,488, a vasopressin receptor antagonist dPTyr(Me)AVP or an N
      methyl-D-aspartate (NMDA) receptor antagonist MK-801) on the development of
      morphine tolerance in rat hippocampal slices. 2. Hippocampal slices (450 microm)
      of Sprague-Dawley rats (250-300 g) were used. Slices were continuously superfused
      with artificial CSF or drugs at 1 ml min(-1). Nichrome wire electrodes were
      placed in the Schaffer-collateral pathway and used to deliver biphasic 0.2 ms
      pulses of 5-30 V (0.033 Hz). A glass microelectrode was placed in the CA1 area to
      record population spikes. 3. When the slices were superfused with 10 microM
      morphine, the amplitude of population spikes increased 2-3 fold in 30-40 min.
      However, this effect of morphine decreased, i.e. tolerance developed after
      continuous superfusion of morphine for 2-6 h. 4. When either U-50,488 (200 nM) or
      dPTyr(Me) AVP (500 pM) or MK-801 (500 pM) was co-superfused with morphine (10
      microM), it significantly blocked the development of morphine tolerance. Nor-BNI
      (a kappa-opioid receptor antagonist, 200 nM) significantly reversed the
      inhibitory effect of U-50,488 but not those of dPTyr(Me)AVP or MK-801 on the
      development of morphine tolerance. 5. These data indicate that kappa-opioid
      receptors, AVP receptors and NMDA receptors are all involved in the development
      of morphine tolerance. The suppression of kappa-opioid receptor activity after
      chronic morphine may occur before the activation of AVP receptors or NMDA
      receptors during the development of morphine tolerance.

PMID- 9517383
TI  - Modulation of transcription factor NF-kappaB by enantiomers of the nonsteroidal
      drug ibuprofen.
AB  - 1. The nonsteroidal drug ibuprofen exists as an R(-)- and S(+)-enantiomer. Only
      the S(+)-enantiomer is an effective cyclo-oxygenase inhibitor, while the R(-)
      enantiomer is inactive in this respect. Thus the molecular mechanism by which R(
      )-ibuprofen exerts its anti-inflammatory and antinociceptive effects remains
      unknown. 2. In this study the effects of the enantiomers of ibuprofen on
      modulation of transcription factors have been examined with electrophoretic
      mobility-shift assay (EMSA), transient transfection experiments, confocal
      immunofluorescence and nuclear import experiments, to determine their selectivity
      and potency as inhibitors of the activation of transcription factor nuclear
      factor-kappaB (NF-kappaB). 3. R(-)-ibuprofen (IC50: 121.8 microM) as well as the
      S(+)-enantiomer (IC50: 61.7 microM) inhibited the activation of NF-kappaB in
      response to T-cell stimulation. The effect of ibuprofen was specific because, at
      concentrations up to 10 mM, ibuprofen did not affect the heat shock transcription
      factor (HSF) and the activation of NF-kappaB by prostaglandin E2 (PGE2). Very
      high concentrations of ibuprofen (20 mM) did not prevent NF-kappaB binding to DNA
      in vitro. Immunofluorescence and nuclear import experiments indicate that the
      site of ibuprofen action appeared to be upstream of the dissociation of the NF
      kappaB-IkappaB-complex. 4. Our data raise the possibility that R(-)-ibuprofen
      exerts some of its effects by inhibition of NF-kappaB activation.

PMID- 9517382
TI  - Mechanisms of acute vasodilator response to bacterial lipopolysaccharide in the
      rat coronary microcirculation.
AB  - 1. In this study the mechanisms of the acute vasodilator action of bacterial
      lipopolysaccharide (LPS) were investigated in the rat Langendorff perfused heart.
      2. Infusion of LPS (5 microg ml(-1)) caused a rapid and sustained fall in
      coronary perfusion pressure (PP) of 59 +/- 4 mmHg (n = 12) and a biphasic
      increase in NO levels determined in the coronary effluent by chemiluminescent
      detection. Both the fall in PP and the increase in NO release were completely
      abolished (n = 3) by pretreatment of hearts with the NO synthase inhibitor L-NAME
      (50 microM). 3. LPS-induced vasodilatation was markedly attenuated to 5 +/- 4
      mmHg (n 3) by pretreatment of hearts with the B2 kinin receptor antagonist Hoe
      140 (100 nM). 4. Vasodilator responses to LPS were also blocked by brief
      pretreatment with mepacrine (0.5 microM, n = 3) or nordihydroguaiaretic acid (0.1
      microM, n = 4) and markedly attenuated by WEB 2086 (3 microM, n = 4). 5. Thirty
      minutes pretreatment of hearts with dexamethasone (1 nM), but not progesterone (1
      microM), significantly modified responses to LPS. The action of dexamethasone was
      time-dependent, having no effect when applied either simultaneously with or pre
      perfused for 5 min before the administration of LPS but inhibiting the response
      to LPS by 91 +/- 1% (n = 4) when pre-perfused for 15 min. The inhibition caused
      by dexamethasone was blocked by 15 min pretreatment with the glucocorticoid
      receptor antagonist RU-486 (100 nM) or by 2 min pre-perfusion of a 1:200 dilution
      of LCPS1, a selective antilipocortin 1 (LC1) neutralizing antibody. 6. Treatment
      with the protein synthesis inhibitor, cycloheximide (10 microM, for 15 min)
      selectively blunted LPS-induced vasodilatation, reducing the latter to 3 +/- 5
      mmHg (n = 3), while having no effect on vasodilator responses to either
      bradykinin or sodium nitroprusside. 7. These results indicate that LPS-induced
      vasodilatation in the rat heart is dependent on activation of kinin B2 receptors
      and synthesis of NO. In addition, phospholipase A2 (PLA2) is activated by LPS
      resulting in the release of platelet-activating factor (PAF) and lipoxygenase but
      not cyclo-oxygenase products. These effects are dependent on de novo synthesis of
      an intermediate protein which remains to be identified.

PMID- 9517384
TI  - Functional and morphological damage of endothelium in rabbit ear artery following
      irradiation with cobalt60.
AB  - 1. The relaxant actions of acetylcholine and A23187 were examined in the rabbit
      central ear artery at different intervals following exposure to different doses
      of radiation with a cobalt60 unit. The artery was irradiated with a dose of 10
      Gy, 20 Gy and 45 Gy. Radiation caused dose- and time-dependent impairment of the
      endothelium-dependent relaxations. The impaired endothelium-dependent relaxations
      occurred as early as 1 week postirradiation and persisted throughout the
      experimental period (10 weeks). 2. The endothelium-independent response to sodium
      nitroprusside was well preserved up to 6 weeks after irradiation. The contractile
      response to noradrenaline was unaltered by irradiation throughout the
      experimental period, but in contrast to control vessels, an increase in the
      sensitivity to noradrenaline in the presence of the nitric oxide synthase (NOS)
      inhibitor N(G)-nitro-L-arginine was not observed in the irradiated vessels. 3.
      The impaired endothelium-dependent relaxations in the irradiated vessels were not
      improved by pretreatment with the NOS substrate L-arginine, the cyclo-oxygenase
      inhibitor indomethacin or the free radical scavengers superoxide dismutase and
      catalase. 4. Scanning electron microscopy indicated morphologically intact
      endothelial cells within the first 4 weeks after irradiation. 5. Western blot
      analysis showed a significant decrease in the expression of endothelial NOS
      (eNOS) in the irradiated vessels. 6. These data indicate that endothelial cell
      function is specifically impaired in the irradiated vessels before morphological
      endothelial cell damage can be detected. This impairment may be related to
      diminished eNOS expression.

PMID- 9517385
TI  - Different efficacy of specific agonists at 5-HT3 receptor splice variants: the
      role of the extra six amino acid segment.
AB  - 1. Whole cell voltage clamp electrophysiology and radioligand binding were used
      to examine the agonist characteristics of the two splice variants of the 5-HT3
      receptor which have been cloned from neuronal cell lines. Homo-oligomeric 5-HT3
      receptors were examined in HEK 293 cells stably transfected with either long (5
      HT3-L) or short (5-HT3-S) receptor subunit DNAs. 2. Functional homo-oligomeric
      receptors were formed from both subunits, and responses to 5-HT3 receptor
      agonists (5-hydroxytryptamine (5-HT), 2-methyl 5-HT and m-chlorophenylbiguanide)
      were qualitatively similar. 3. Maximum currents (Rmax) elicited by the 5-HT3
      receptor agonists m-chlorophenylbiguanide (mCPBG) and 2-methyl-5-HT (2-Me-5-HT),
      as compared to 5-HT, differed in the two splice variants: Rmax mCPBG/Rmax 5-HT
      values were 0.68+/-0.04 and 0.91+/-0.01 in 5-HT3-L and 5-HT3-S receptors,
      respectively. Comparable values for 2-Me-5-HT were 0.30+/-0.02 and 0.23+/-0.02.
      4. Radioligand binding data showed no difference in affinity of agonist or
      antagonist binding sites; thus the six amino acid deletion appears to cause
      differences in agonist efficacy. 5. The role of the 6 amino acid insertion was
      further investigated by use of site-directed mutagenesis to create two mutant
      receptors, one where serine 286 was replaced with alanine, and the second where
      all 6 amino acids were replaced with alanines. 6. Examination of the mutant
      receptors when stably expressed in HEK 293 cells revealed agonist properties
      resembling long and not short 5-HT3 receptors. Thus specific amino acids in this
      region are not responsible for the observed differences. 7. The data show
      intracellular structure can have significant effects on ligand-gated ion channel
      function, and suggest that minor changes in structure may be responsible for
      differences in function observed when ligand-gated ion channel proteins are
      modulated intracellularly.

PMID- 9517387
TI  - Inhibitory action of insulin-sensitizing agents on calcium channels in smooth
      muscle cells from resistance arteries of guinea-pig.
AB  - 1. The actions of troglitazone, pioglitazone, metformin and bezafibrate, agents
      that improve insulin-resistance, on voltage-dependent Ca2+ channels in arterial
      smooth muscle cells were examined by use of the conventional and nystatin
      perforated whole-cell clamp methods. Single cells were freshly isolated from
      resistance mesenteric arteries of guinea-pigs. The actions of these agents on 77
      mM K+-induced contraction of the isolated arteries were also examined with the
      use of isometric tension recording. 2. The thiazolidinedione derivatives,
      troglitazone and pioglitazone, inhibited whole-cell Ca2+ currents in a dose
      dependent manner with dissociation constants of 3.0 microM and 44.9 microM and
      Hill coefficients of 0.61 and 0.68, respectively. These two agents inhibited the
      77 mM K+-induced contraction with similar potencies as those inhibiting the Ca2+
      currents. Metformin and bezafibrate had no apparent effects on the Ca2+ current
      or high K+-induced contraction. 3. The inhibitory action of troglitazone on Ca2+
      currents was not affected by the command potential, the holding potential, or the
      stimulation frequency, suggesting that its mode of the action differs from that
      of known organic Ca2+ channel antagonists. 4. The inhibitory action of
      troglitazone on Ca2+ currents was not affected by the addition of insulin to, or
      the removal of glucose from, the solutions. 5. In conclusion, the
      thiazolidinedione derivatives directly inhibited the voltage-dependent Ca2+
      channels in a different manner from that of organic Ca2+ channel antagonists.
      This inhibitory action on Ca2+ channels was not a common feature of insulin
      sensitizing agents.

PMID- 9517386
TI  - Metabotropic glutamate receptors depress glutamate-mediated synaptic input to rat
      midbrain dopamine neurones in vitro.
AB  - 1. Glutamate (AMPA receptor-mediated) excitatory postsynaptic potentials
      (e.p.s.ps.), evoked by electrical stimulation rostral to the recording site, were
      examined by intracellular microelectrode recording from dopamine neurones in
      parasagittal slices of rat ventral midbrain. 2. The e.p.s.p. was depressed by the
      group III metabotropic glutamate (mGlu) receptor agonist L-2-amino-4
      phosphonobutyric acid (L-AP4; 0.01-30 microM) by up to 60% with an EC50 of 0.82
      microM. The depression induced by L-AP4 (3 microM) was reversed by the group III
      preferring mGlu receptor antagonist, alpha-methyl-4-phosphonophenylglycine (MPPG;
      250 microM). 3. The group I and II mGlu agonist, 1S,3R
      aminocyclopentanedicarboxylic acid (ACPD; 3-30 microM) also depressed the
      e.p.s.p. in a concentration-dependent manner. The effect of ACPD (10 microM) was
      reversed by (+)-alpha-methyl-4-carboxyphenylglycine (MCPG; 1 mM; 4 cells). This
      effect of ACPD was also partially antagonized (by 50.3+/-15.7%, 4 cells) by MPPG
      (250 microM). 4. The selective agonist at group I mGlu receptors,
      dihydroxyphenylglycine (DHPG; 100 microM), decreased e.p.s.p. amplitude by 27.1+/
      8.2% (7 cells), as did the group II mGlu receptor-selective agonist
      (1S,1R,2'R,3'R)-2-(2,3-dicarboxycyclopropyl)glycine (DCG-IV; 1 microM) by 26.7+/
      4.3% (5 cells). 5. DHPG (10-100 microM) caused a depolarization of the recorded
      cell, as did ACPD (3-30 microM), whereas no such postsynaptic effect of either L
      AP4 or DCG-IV was observed. 6. These results provide evidence for the presence of
      presynaptic inhibitory metabotropic glutamate autoreceptors from the mGlu
      receptor groups II and III on descending glutamatergic inputs to midbrain
      dopamine neurones. Group I mGlu receptors mediate a postsynaptic depolarization,
      and can also depress glutamatergic transmission, but may not necessarily be
      localized presynaptically. These sites represent novel drug targets for treatment
      of schizophrenia and movement disorders of basal ganglia origin.

PMID- 9517388
TI  - Structural basis for specificity and potency of xanthine derivatives as
      activators of the CFTR chloride channel.
AB  - 1. On the basis of their structure, we compared the ability of 35 xanthine
      derivatives to activate the cystic fibrosis transmembrane conductance regulator
      (CFTR) chloride channel stably expressed in chinese hamster ovary (CHO) cells
      using the cell-attached patch clamp and iodide efflux techniques. 2. Activation
      of CFTR channels was obtained with 3-mono, 1,3-di or 1,3,7-tri-substituted alkyl
      xanthine derivatives (enprofylline, theophylline, aminophylline, IBMX, DPMX and
      pentoxifylline). By contrast, xanthine derivatives substituted at the C8- or N9
      position failed to open CFTR channels. 3. The CFTR chloride channel activity was
      blocked by glibenclamide (100 microM) but not by DIDS (100 microM). 4. Activation
      of CFTR by xanthines was not mimicked by the calcium ionophore A23187, adenosine,
      UTP, ATP or the specific phosphodiesterase inhibitors rolipram, Ro 20-1724 and
      milrinone. In addition, we found no correlation between the effect of xanthines
      on CFTR and on the cellular cyclic AMP or ATP levels. 5. We then synthesized a
      series of 3,7-dimethyl-1-alkyl xanthine derivatives; among them, 3,7-dimethyl-1
      propyl xanthine and 3,7-dimethyl-1-isobutyl xanthine both activated CFTR channels
      without increasing the intracellular cyclic AMP level, while the structurally
      related 3,7-dimethyl-1-(2-propenyl) xanthine and 3,7-dimethyl-1-(oxiranyl methyl)
      xanthine were inactive. 6. Our findings delineate a novel function for xanthine
      compounds and identify the molecular features that enable xanthine activation of
      CFTR. These results may be useful in the development of new molecules for
      studying the pharmacology of chloride channels.

PMID- 9517389
TI  - The relevance of resting tension to responsiveness and inherent tone of human
      bronchial smooth muscle.
AB  - 1. In the present study the effects of resting tension on isometric responses of
      human airway smooth muscle to contractile and relaxant stimuli were investigated.
      Also, its effects on inherent smooth muscle tone were examined, in an effort to
      determine a pre-defined resting tension which can be considered optimal for in
      vitro studies. 2. Bronchial ring preparations (2-4 mm internal diameter) were
      suspended in tissue baths at a range of levels of resting tension (200-1600 mg).
      The responses to electrical field stimulation (EFS, 30 V, 0.2 ms, 8-30 Hz),
      carbachol (3 microM), isoprenaline (1 microM) and the 5-lipoxygenase inhibitor,
      zileuton (10 microM) were investigated along with the ability of the preparations
      to recover stable resting tension after 60 min of washing post challenge. 3. EFS
      induced monophasic contractions at low stimulation frequency (8 Hz). However,
      with increasing frequency and tension (15 and 30 Hz; > 400 mg) contractile
      responses were accompanied by a relaxant component. The magnitude of contractile
      responses increased with increasing resting tension to a plateau at between 500
      and 700 mg. Relaxant responses when present, increased in magnitude with
      increasing resting tension. 4. The level of resting tension did not significantly
      alter responses to carbachol, but tissues at tensions > or = 1000 mg showed poor
      tension recovery after washing. Isoprenaline-induced relaxations increased with
      increasing resting tension (P<0.05) and tension recovery after washing was
      complete. The 5-lipoxygenase sensitive portion of the tension (33+/-4%) was not
      altered by the level of resting tension. 5 These results suggest that in human
      bronchial ring preparations of 2-4 mm internal diameter, resting tensions within
      the range 400-1000 mg could be considered optimal for isometric tension
      recordings of protocols involving both contraction and relaxation procedures.

PMID- 9517390
TI  - Salmeterol-induced desensitization, internalization and phosphorylation of the
      human beta2-adrenoceptor.
AB  - 1. Partial agonists of the beta2-adrenoceptor which activate adenylyl cyclase are
      widely used as bronchodilators for the relief of bronchoconstriction accompanying
      many disease conditions, including bronchial asthma. The bronchodilator
      salmeterol has both a prolonged duration of action in bronchial tissue and the
      ability to reassert this activity following the temporary blockade of human beta2
      adrenoceptors with antagonist. 2. We have compared the activation and
      desensitization of human beta2-adrenoceptor stimulation of adenylyl cyclase
      induced by salmeterol, adrenaline and salbutamol in a human lung epithelial line,
      BEAS-2B, expressing beta2-adrenoceptor levels of 40-70 fmol mg(-1), and in human
      embryonic kidney (HEK) 293 cell lines expressing 2-10 pmol mg(-1). The efficacy
      observed for the stimulation of adenylyl cyclase by salmeterol was only
      approximately 10% of that observed for adrenaline in BEAS-2B cells expressing low
      levels of beta2-adrenoceptor, but similar to adrenaline in HEK 293 cells
      expressing very high levels of receptors. Salmeterol pretreatment of these cells
      induced a rapid and stable activation of adenylyl cyclase activity which resisted
      extensive washing and beta2-adrenoceptor antagonist blockade, consistent with
      binding to a receptor exosite and/or to partitioning into membrane lipid. 3. The
      desensitization and internalization of beta2-adrenoceptors induced by the partial
      agonists salmeterol and salbutamol were considerably reduced relative to the
      action of adrenaline. Consistent with these observations, the initial rate of
      phosphorylation of the receptor induced by salmeterol and salbutamol was much
      reduced in comparison to adrenaline. 4. Our data suggest that the reduction in
      the rapid phase of desensitization of beta2-adrenoceptors after treatment with
      salmeterol or salbutamol is caused by a decrease in the rate of beta2
      adrenoceptor kinase (betaARK) phosphorylation and internalization. In contrast,
      the rate of cyclic AMP-dependent protein kinase (PKA)-mediated phosphorylation by
      these partial agonists appears to be similar to adrenaline.

PMID- 9517391
TI  - Transition of functional innervation in the developing porcine airway from
      nitrergic to catecholaminergic.
AB  - 1. We determined the distribution and chemical nature of the inhibitory
      neurotransmitter(s) to the airway smooth muscle (ASM) before and after birth. 2.
      Relaxation responses to electrical field stimulation (EFS) were studied in
      isovolumic bronchial segments from foetal (approximately 100/115 days gestation)
      and adult (25 kg) pigs, and in isovolumic tracheal segments from the foetus, and
      tracheal smooth muscle strips from the adult pig. Preparations were conditioned
      in low doses of atropine (10(-7) M) to reduce the effects of excitatory
      neurotransmission and then exposed to carbachol to produce submaximal muscle
      tone. Some studies were also carried out on bronchial segments from 4 week old
      pigs. 3. EFS (65 V, 2 ms, 5-20 Hz for 5 s) produced a TTX-sensitive relaxation in
      epithelium-intact and epithelium-denuded preparations. In foetal bronchial and
      tracheal preparations, EFS-induced relaxation was strongly inhibited by N(G)
      nitro-L-arginine (L-NOARG, 10(-6) to 10(-4) M; P<0.01-0.001). However, in the
      adult, only relaxations of the trachea were inhibited by L-NOARG; bronchi were
      resistant to L-NOARG and also to N-nitro-L-arginine methyl ester (L-NAME, 10(-4)
      M). The inhibitory actions of L-NOARG (10(-6) to 10(-4) M) were substantially
      reversed by 10(-2) M L-arginine. Experiments with bronchial segments from 4 week
      old pigs showed partial inhibition of relaxations by L-NOARG. 4. The L-NOARG
      insensitive relaxations recorded in the adult bronchus were blocked by
      propranolol (10(-6) M). 5. The onset of relaxation to EFS was more prompt and the
      rate of relaxation more rapid in foetal bronchi than in adult bronchi (P<0.0005).
      Maximum relaxation and recovery times were the same. 6. Foetal and adult bronchi
      were relaxed by sodium nitroprusside (SNP) with similar sensitivity and maximum
      effect. The rate of relaxation to SNP was not different in the two ages. 7. In
      the absence of atropine and carbachol, excitatory cholinergic responses to EFS
      (65 V, 2 ms, 5 Hz for 20 s) were not altered by L-NOARG (10(-4) M) or L-NAME (10(
      4) M) in the adult bronchus but were modestly increased by L-NOARG in the foetal
      bronchus (P<0.01). 8. The tracheobronchial tree appears functionally innervated
      by nitrergic input to the smooth muscle before birth. However, at or after 4
      weeks of age the inhibitory neural input to the bronchi is catecholaminergic, but
      it remains nitrergic in the trachea. There is also a weak nitrergic pre- or
      postsynaptic inhibition of the effects of cholinergic neurotransmission in the
      foetal bronchus but not in the adult.

PMID- 9517392
TI  - P2U-receptor mediated endothelium-dependent but nitric oxide-independent vascular
      relaxation.
AB  - 1. The dilator effect of extracellular adenosine triphosphate (ATP) has mainly
      been characterized as a direct effect on smooth muscle or as an endothelium
      dependent effect mediated by nitric oxide (NO) or prostaglandins. We tested the
      hypothesis that endothelium-derived hyperpolarizing factor (EDHF) may also be
      involved. Dilator effects were studied in vitro by continuous recording of
      isomeric tension in cylindrical segments of rat blood vessels precontracted by
      noradrenaline (NA), in the presence of indomethacin (10 microM). 2. By screening
      different blood vessels in the rat we found that both acetylcholine (ACh) and ATP
      dilate mesenteric arteries with a resting tone of 1 mN by an endothelium
      dependent non-NO mechanism. With an increased resting tone (4 mN) the dilatation
      was mediated by NO. Thus by varying the resting tension the different dilator
      mechanisms could be examined. However, in the carotid artery the dilatation was
      solely mediated by an endothelium-dependent NO mechanism, even at different
      resting tones (1 and 4 mN). 3. The N-nitro-L-arginine methyl ester (L-NAME)
      resistant dilatation to ACh and ATP was further inhibited by the NO-scavenger 2
      phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (PTIO), indicating L-NAME
      insensitive NO-synthesis. 4. In carotid arteries and mesenteric arteries at high
      resting tones (4 mN) the ATP-dilatation was totally inhibited by endothelium
      removal or L-NAME (10(-3) M). In mesenteric arteries at low resting tone (1 mN)
      the ATP, UTP (uridine-triphosphate) and 2-MeSATP (2methylthioATP)-dilatation was
      totally inhibited by endothelium removal. However, L-NAME in combination with
      indomethacin attenuated only 5% of the UTP dilatation, 70% of the ATP dilatation
      but all of the 2-MeSATP-dilatation. The inhibitors of Ca2+-activated K+ channels
      charybdotoxin (0.5 x 10(-7) M) together with apamin (10(-6) M), and the
      cytochrome P450 inhibitor, SKF 525A (10(-4) M), each in combination with
      indomethacin. L-NAME and PTIO (0.5 x 10(-3) M) totally abolished the remaining
      ATP and UTP-dilatation. This indicates a dilatation mediated by an endothelium
      dependent non-NO factor, probably EDHF. 5. Agonist potency (UTP>ATP>>2-MeSATP),
      indicates that the EDHF-mediated dilatation was stimulated by a P2U-receptor,
      possibly by a selective pyrimidine-receptor. In contrast, a P2Y-receptor
      stimulated NO-mediated dilatation (2-MeSATP=ATP>UTP). 6. In conclusion, the
      dilator effects of ATP and especially UTP can be mediated by an endothelium
      dependent non-NO-mediated mechanism, probably EDHF, mediated by a P2U-receptor,
      possibly a selective pyrimidine-receptor, while NO-mediated dilatation is
      stimulated mainly by a P2Y1-receptor. Furthermore, the EDHF-dilatation is
      dependent on the resting tone of the blood vessel.

PMID- 9517393
TI  - Pharmacological evidence for the presence of a peripheral postjunctional D2-like
      dopamine receptor in rabbit splenic artery.
AB  - 1. This study was designed to investigate the involvement of postjunctional D2
      like receptors in a rabbit vasculature model used to evaluate the D1-like agonist
      activity. Dopamine, epinine and (-)-DP-5,6-ADTN, three mixed D1/D2-like agonists,
      fenoldopam and SKF 82958, two selective D1-like agonists and SKF 89124, a
      selective D2-like agonist, were administered cumulatively in precontracted and
      alpha/beta-blocked rabbit splenic artery rings in order to evaluate their D1-like
      mediated vasorelaxant activity before and after pretreatment with the selective
      D2-like antagonist YM 09151-2 (1 nM). 2. Dopamine (pD2=6.35+/-0.09), epinine
      (pD2=6.73+/-0.13), (-)-DP-5,6-ADTN (pD2=7.56+/-0.09) and SKF 82958 (pD2=8.55+/
      0.10) reversed completely the U46619-induced contracture whereas SKF 89124 was
      inactive up to 10 microM and fenoldopam acted like a partial agonist (pD2=8.31+/
      0.09, alpha=0.62). The selective D2-like dopamine receptor antagonist YM 09151-2
      (1 nM) significantly (P<0.05) potentiated the vasorelaxant activity of dopamine
      (pD2=7.01+/-0.07), epinine (pD2=7.14+/-0.08), (-)-DP-5,6-ADTN (pD2=8.19+/-0.09)
      and SKF 89124 (40% relaxation at 10 microM), whereas it did not alter the effects
      of fenoldopam (pD2=8.40+/-0.09, alpha=0.68) and SKF 82958 (pD2=8.58+/-0.08). 3.
      The D2-like antagonist YM 09151-2 induced the same degree of effect with all the
      substances tested in both endothelium-denuded and endothelium-intact
      preparations. 4. The selective D2-like dopamine receptor agonist SKF 89124 did
      not produce any intrinsic effect on the splenic artery, but was able to produce a
      rightward shift of the forskolin-induced relaxation. 5. The results of these
      experiments support the existence of a non-endothelial postjunctional D2-like
      dopamine receptor counteracting the D1-like-mediated vasodilatation in rabbit
      splenic artery, probably by the inhibition of adenylate cyclase.

PMID- 9517394
TI  - Mechanism of antidiuresis caused by bendroflumethiazide in conscious rats with
      diabetes insipidus.
AB  - 1. The mechanism underlying the antidiuretic effect of thiazide diuretics in
      diabetes insipidus (DI) is unknown. This study addressed two specific questions:
      is the reduction in urine flow rate (V) related to a decrease in the delivery of
      fluid from the pars recta of the proximal tubules ('distal delivery'), and are
      there any changes in the expression and/or intracellular distribution of
      vasopressin stimulated water channels (AQP2) in the collecting ducts, during
      chronic thiazide-induced antidiuresis? 2. Nine Brattleboro rats with vasopressin
      deficient DI were treated for 5 days with bendroflumethiazide (BFTZ), 9 mg kg(-1)
      day(-1) orally, and 9 Brattleboro rats were left untreated. BFTZ-treated DI rats
      showed a fall in V from approximately 200 to approximately 75 ml day(-1) and an
      increase in urine osmolality from approximately 130 to approximately 400 mosmol
      kg(-1). 3. BFTZ-induced antidiuresis was associated with a persistent loss of
      sodium, but not of potassium. After 5 days of treatment, clearance studies in
      conscious rats showed a tendency towards decreases in effective renal plasma flow
      (-7%), GFR (-12%) and lithium clearance (C(Li); used as marker for distal
      delivery) (-25%), compared with untreated controls, but none of these changes
      were statistically significant. There was no apparent relationship between C(Li)
      and V in BFTZ-treated or untreated DI rats. 4. BFTZ treatment did not change the
      expression of AQP2 in homogenates of cortex, outer or inner medulla from DI rats,
      or from normal Long Evans rats. Light and electron microscopic
      immunocytochemistry revealed no changes in intracellular distribution of AQP2 in
      principal cells from inner medullary collecting ducts of BFTZ-treated DI rats. 5.
      We concluded, (i) that although the antidiuretic effect of BFTZ in rats with DI
      is associated with a net loss of Na, the decrease in V shows no association with
      changes in distal delivery, as estimated by C(Li). (ii) Antidiuretic treatment
      with BFTZ does not alter the expression of subcellular distribution of AQP2 water
      channels in the collecting ducts. The mechanism underlying the chronic
      antidiuresis caused by thiazide diuretics in DI remains elusive.

PMID- 9517395
TI  - Influence of excitatory amino acids on basal and sensory stimuli-induced release
      of 5-HT in the locus coeruleus.
AB  - 1. The interactions between 5-hydroxytryptaminergic neurones and excitatory amino
      acid utilizing neurones were studied in the locus coeruleus of conscious, freely
      moving rats. The locus coeruleus was superfused with artificial cerebrospinal
      fluid through a push-pull cannula and 5-hydroxytryptamine (5-HT) was determined
      in the superfusate that was continuously collected in time periods of 10 min. 2.
      Superfusion of the locus coeruleus with the NMDA receptor antagonist AP5 (10
      microM), kynurenic acid (1 mM), or the AMPA/kainate receptor antagonist DNQX (10
      microM) reduced the 5-HT release in the locus coeruleus. 3. Superfusion with the
      agonists NMDA (50 microM), kainic acid (50 microM) or AMPA (10 microM) enhanced
      the release rate of 5-HT. AP5 (10 microM) blocked the stimulant effect of NMDA,
      while tetrodotoxin (1 microM) failed to influence the NMDA-induced release of 5
      HT. In the presence of 10 microM DNQX, the releasing effect of 50 microM kainic
      acid was abolished. 4. Pain elicited by tail pinch, as well as noise-induced
      stress, increased the release of 5-HT. Superfusion of the locus coeruleus with 10
      microM AP5 reduced the tail pinch-induced 5-HT release. AP5 (10 microM) did not
      affect the noise-induced release of 5-HT which was reduced, when the locus
      coeruleus was superfused simultaneously with this concentration of AP5 and 1
      microM kynurenic acid. DNQX (10 mM) failed to influence the release of 5-HT
      induced by tail pinch or noise. 5. The findings suggest that 5
      hydroxytryptaminergic neurones of the locus coeruleus are tonically modulated by
      excitatory amino acids via NMDA and AMPA/kainate receptors. The release of 5-HT
      elicited by tail pinch and noise is mediated to a considerable extent through
      endogenous excitatory amino acids acting on NMDA receptors, while AMPA/kainate
      receptors are not involved in this process.

PMID- 9517396
TI  - Relaxant effects of NKH477, a new water-soluble forskolin derivative, on guinea
      pig tracheal smooth muscle: the role of Ca2+-activated K+ channels.
AB  - 1. Mechanisms underlying the bronchorelaxant action of NKH477, a newly developed
      water-soluble forskolin derivative, were investigated in guinea-pig isolated
      tracheal smooth muscle. 2. In muscles precontracted with 3 microM histamine,
      NKH477 (1 nM-1 microM) caused a concentration-dependent decrease of isometric
      tension, resulting in a complete relaxation at 300 nM. The EC550 for the
      relaxation was 32.6+/-4.3 nM (n=6). 3. In the presence of 30 or 90 nM iberiotoxin
      (IbTX), a selective blocker of the large-conductance Ca2+-activated K+ (BK(Ca))
      channel, the relaxing action of NKH477 on the histamine-induced contraction was
      inhibited, giving rise to a parallel shift of the concentration-response curves;
      the EC50 of NKH477 was increased to 131.4+/-20.4 nM at 30 nM IbTX (n=4), and
      125.3+/-12.2 nM at 90 nM IbTX (n=4). 4. Pretreatment of muscles with 30 mM
      tetraethylammonium (TEA) caused a similar rightward shift of the concentration
      response curve to NKH477 with an increase of the EC50 to 139.8+/-18.4 nM (n=5).
      In contrast, the relaxing action of NKH477 was unaffected by 10 microM
      glibenclamide, an ATP-sensitive K channel blocker, or by 100 nM apamin, a blocker
      of small conductance Ca2+-activated K+ channels. 5. In muscles pretreated with 1
      microM nifedipine, a blocker of the voltage-dependent Ca2+ channel (VDC), 30-90
      nM IbTX did not affect the relaxant effects of NKH477 on the histamine-induced
      contraction. 6. In muscles precontracted by a K+-rich (40 mM) solution, NKH477
      caused only minimal relaxation (19.8+/-1.7%, n=4) even at the highest
      concentration (1 microM). 7. In experiments to measure the ratio of fura-2
      fluorescence signals (R(340/380)) as an index of the intracellular Ca2+
      concentration ([Ca2+]i), the application of 100 nM NKH477 or 200 nM isoprenaline
      to the preparation precontracted by 3 microM histamine resulted in a decrease in
      [Ca2+]i in association with a decrease in tension. The reduction of [Ca2+]i and
      tension by NKH477 was 47.0+/-5.6% and 62.8+/-7.0%, respectively (n=5), and that
      with isoprenaline 60.6+/-7.4% and 67.4+/-6.4%, respectively (n=5). These effects
      of NKH477 and isoprenaline on [Ca2+]i and tension were inhibited by 30 nM IbTX.
      The inhibitory action of IbTX was abolished in the presence of 1 microM
      nifedipine. 8. These results suggest that the bronchorelaxant action of NKH477
      may result, at least in part, from activation of BK(Ca) channels, which may cause
      a hyperpolarization of smooth muscle cell membranes and a secondary decrease in
      Ca2+ influx through VDCs, leading to a decrease in [Ca2+]i.

PMID- 9517397
TI  - Comparison of relaxin receptors in rat isolated atria and uterus by use of
      synthetic and native relaxin analogues.
AB  - 1. The receptors for relaxin in the rat atria and uterus were investigated and
      compared by use of a series of synthetic and native relaxin analogues. The assays
      used were the positive chronotropic and inotropic effects in rat spontaneously
      beating, isolated right atrium and electrically driven left atrium and the
      relaxation of K+ precontracted uterine smooth muscle. 2. Relaxin analogues with
      an intact A- and B-chain were active in producing powerful chronotropic and
      inotropic effects in the rat isolated atria at nanomolar concentrations. Single
      chain analogues and structural homologues of relaxin such as human insulin and
      sheep insulin-like growth factor I had no agonist action and did not antagonize
      the effect of the B29 form of human gene 2 relaxin. 3. Shortening the B-chain
      carboxyl terminal of human gene 1 (B2-29) relaxin to B2-26 reduced the activity
      of the peptide and removal of another 2 amino acid residues (B2-24) abolished the
      activity. This suggests that the B-chain length may be important for
      determination of the activity of relaxin. More detailed studies are needed to
      determine the effect of progressive amino acid removal on the structure and the
      bioactivity of relaxin. 4. Porcine prorelaxin was as active as porcine relaxin on
      a molar basis, suggesting that the presence of the intact C-peptide did not
      affect the binding of the prorelaxin to the receptor to produce functional
      responses. 5. Relaxin caused relaxation of uterine longitudinal and circular
      smooth muscle precontracted with 40 mM K+. The pEC50 values for human gene 2 and
      porcine relaxins were lower than those in the atrial assay, but rat relaxin had
      similar pEC50 values in both atrial and uterine assays. Rat relaxin was
      significantly less potent than either human gene 2 or porcine relaxin in the
      atrial assay, but in the uterine assay they were equipotent. The results suggest
      that the relaxin receptor or the signalling pathway in rat atria may differ from
      that in the uterus.

PMID- 9517398
TI  - Potentiation by DL-alpha-aminopimelate of the inhibitory action of a novel mGluR
      agonist (L-F2CCG-I) on monosynaptic excitation in the rat spinal cord.
AB  - 1. Neuropharmacological actions of all the possible stereoisomers of 3',3'
      difluoro-2-(carboxycyclopropyl)glycine (3',3'-difluoro-CCG) were compared with
      those of the corresponding 2-(carboxycyclopropyl)glycine (CCG) isomers in the
      isolated spinal cord of newborn rats. (2S,1'S,2'S)- and (2S,1'R,2'S)-2-(2-carboxy
      3,3-difluorocyclopropyl)glycine (L-F2CCG-I and L-F2CCG-IV) were the most potent
      in causing depolarization, their threshold concentrations being approximately 1
      microM. 2. The depolarization evoked by L-F2CCG-I (30 microM) was depressed by
      (+)-alpha-methyl-4-carboxyphenylglycine (MCPG, 1 mM (n=4)) to 17+/-3% of the
      control: this depolarizing action was not decreased by 6-cyano-7-nitroquinoxaline
      2,3-dione (CNQX, 100 microM), and only slightly decreased by high concentrations
      of D-2-amino-5-phosphonopentanoic acid (D-AP5, 100 microM), suggesting that L
      F2CCG-I activates mainly metabotropic glutamate receptors. 3. L-F2CCG-I
      preferentially depressed the monosynaptic component of the spinal reflex
      approximately 3 times more effectively than (2S,1'S,2'S)-2
      (carboxycyclopropyl)glycine (L-CCG-I). The depressant action of L-F2CCG-I (0.2
      microM-0.7 microM) on monosynaptic excitation was antagonized by (2S,1'S,2'S)-2
      methyl-2-(carboxycyclopropyl)glycine (MCCG, 0.3 mM-1 mM) and (S)-2-amino-2-methyl
      4-phosphonobutanoic acid (MAP4, 0.3 mM). 4. DL-alpha-aminopimelate (10 and 100
      microM) selectively potentiated the depression of monosynaptic excitation caused
      by L-CCG-I (0.2 microM) and L-F2CCG-I (0.1 microM). The actions of
      (2S,1'R,2'R,3'R)-2-(2,3-dicarboxycyclopropyl)glycine (DCG-IV) (50 nM-0.2 microM),
      L-2-amino-4-phosphonobutanoic acid (L-AP4) (0.3-1 microM), (1S,3R)-1
      aminocyclopentane-1,3-dicarboxylic acid ((1S,3R)-ACPD) (1-7 microM) and baclofen
      (0.1-0.7 microM) were unaffected by DL-alpha-aminopimelate. The threshold
      concentration for the potentiating actions of DL-alpha-aminopimelate was 3
      microM. 5. The depolarization induced by quisqualate (3 microM, 10 s application)
      was increased to 115+/-2% and 137+/-5% of the control values during combined
      application of quisqualate with either 30 microM or 100 microM DL-alpha
      aminopimelate, respectively. 6. Following the application and subsequent washout
      of L-F2CCG-I, DL-alpha-aminopimelate (3-100 microM) decreased the amplitude of
      the monosynaptic component of spinal reflexes in a concentration-dependent
      manner, indicating a 'priming' effect of L-F2CCG-I.

PMID- 9517399
TI  - The role of glutamate in physical dependence on opioids.
AB  - The present review will evaluate the interactions between kappa-opioid receptors
      and glutamate within the locus coeruleus (LC) during the development of opioid
      dependence and on expression of withdrawal from dependence on opioids.
      Hyperactivity of noradrenergic neurons in the LC has been proposed to play a
      critical role in the physiological and behavioral responses that comprise opioid
      withdrawal. Several studies indicate that the excitatory amino acid system, in
      particular, glutamate and its receptors, participate in both the withdrawal
      associated increase in LC neuronal activity and the expression of opioid
      withdrawal behaviors. Most studies on opioid dependence have focused on the
      prototypical opioid morphine, which produces its physical dependence through
      agonist actions at the mu-opioid receptor. Butorphanol (Stadol), which exhibits a
      markedly different profile of opioid receptor activity than does morphine,
      produces its physical dependence primarily through actions at the kappa-opioid
      receptor. Studies from our laboratories using a rodent model in which butorphanol
      administration induces dependence indicate further that the kappa-opioid receptor
      is an important regulator of glutamate release within the LC. Glutamate exerts
      actions within the LC that mediate expression of behavioral symptoms of
      butorphanol withdrawal.

PMID- 9517400
TI  - Involvement of spinal substance P and excitatory amino acids in inflammatory
      hyperalgesia in rats.
AB  - To reveal possible involvement of NK-1 substance P receptors and N-methyl-D
      aspartate (NMDA) and non-NMDA glutamate receptors in the production of
      inflammatory hyperalgesia, we examined the effects of intrathecal injections of
      antagonists at those receptors on the nociceptive threshold of inflammatory
      hyperalgesic rats in the paw-pressure test. Intrathecal injections of the NK-1
      antagonist CP-96,345 (0.3-3 nmol/rat), the NMDA antagonist D-2-amino-5
      phosphonovaleric acid (D-APV, 1-10 nmol/rat), and the non-NMDA antagonist 6-cyano
      7-nitroquinoxaline-2,3-dione (CNQX, 1-10 nmol/rat) dose-dependently suppressed
      adjuvant- and carrageenin-induced hyperalgesia, without effect on the nociceptive
      threshold of non-inflamed paws. Furthermore, to estimate whether inflammatory
      hyperalgesia is accompanied with an alteration of the responsiveness to substance
      P and excitatory amino acids, we examined the effects of injections of complete
      Freund's adjuvant (intradermal) and carrageenin (subcutaneous) on the aversive
      responses to intrathecal substance P and excitatory amino acid agonists. Both
      injections significantly potentiated the aversive behaviors elicited by
      intrathecal injections of excitatory amino acid agonists, NMDA (1 nmol/rat), a
      amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA, 1 nmol/rat) and kainate (1
      nmol/rat), but not those by substance P. The present results suggest that the
      enhancement of synaptic transmission mediated by substance P and excitatory amino
      acids in the spinal dorsal horn is at least partly involved in the production of
      inflammatory hyperalgesia, and that such a hyperalgesia is accompanied with the
      enhanced responsiveness to excitatory amino acids through NMDA and non-NMDA
      receptors, but not with changes in responsiveness to substance P.

PMID- 9517401
TI  - Protective effect of GTS-21, a novel nicotinic receptor agonist, on delayed
      neuronal death induced by ischemia in gerbils.
AB  - The neuroprotective effects of GTS-21 [3-(2,4-dimethoxybenzylidene)-anabaseine
      dihydrochloride] were studied and compared with those of nicotine, 9-amino
      1,2,3,4-tetrahydroacridine hydrochloride hydrate (THA) and pentobarbital-Na (PB)
      using a cerebral ischemia model in Mongolian gerbils. The learning performance
      and memory retention were elucidated by a step-through passive avoidance task at
      2 and 3 days after ischemia-reperfusion. In this task, the ischemia-operated
      gerbils showed impairment of learning performance and memory retention. Neuronal
      cell death in the hippocampal CA1 area was observed at 7 days after ischemia.
      When administered i.p. 30 min before ischemia, GTS-21 (5 mg/kg), (-)-nicotine
      (1.5 mg/kg), THA (5 mg/kg) and PB (50 mg/kg) significantly attenuated the
      impairment of passive avoidance performance and the neuronal cell death induced
      by the ischemia. When administered orally twice daily for 2 weeks prior to the
      ischemia, GTS-21 (10 mg/kg) significantly suppressed both amnesia and neuronal
      cell death, while (-)-nicotine (10 mg/kg) and THA (10 mg/kg) suppressed only the
      amnesia. These results suggest that GTS-21 exerts a protective activity on not
      only impairment of learning and memory but also delayed neuronal death and that
      the underlying mechanism of GTS-21 differs from that of nicotine or THA.

PMID- 9517402
TI  - Inhibition of delayed rectifier K+ current by dofetilide and E-4031
      differentially affects electrical cardiac responses to vagus stimulation in
      anesthetized dogs.
AB  - Vagal activation influences various cardiac functions as well as occurrence of
      arrhythmias. Inhibition of a rapid type of delayed rectifier K+ current (I[Kr])
      has been reported to be effective for the treatment of both ventricular and
      supraventricular arrhythmias. However, it is unknown how I[Kr] inhibition
      modulates the cardiac responses to vagal activation in situ. We analyzed the
      effects of I[Kr] inhibitors, dofetilide and E-4031, and a class I antiarrhythmic
      agent, disopyramide, on electrical cardiac responses to vagus stimulation in
      anesthetized dogs. Dofetilide (0.003-0.3 micromol/kg, i.v.), E-4031 (0.01-1
      micromol/kg, i.v.) and disopyramide (2.9-29 micromol/kg, i.v.) prolonged sinus
      cycle length (SCL), right atrial effective refractory period (AERP) and
      ventricular effective refractory period (VERP) dose-dependently. During cervical
      vagus stimulation-induced prolongation of SCL, atrio-His (AH) interval and VERP
      and shortening of AERP, dofetilide and E-4031 inhibited the prolongation of SCL
      but potentiated the shortening of AERP. Dofetilide and E-4031 did not affect
      prolongations of AH interval and VERP. On the other hand, disopyramide inhibited
      all electrical cardiac responses to vagus stimulation. These results suggest that
      I(Kr) inhibition differentially modulate cardiac responses to vagus activation
      probably due to a different role of I(Kr) in each cardiac function in the heart
      in situ.

PMID- 9517403
TI  - Renal endothelin in FK506-induced nephrotoxicity in spontaneously hypertensive
      rats.
AB  - FK506, a major immunosuppressive agent, often causes nephrotoxicity accompanied
      by renal vasoconstriction. It is recognized that endothelin (ET) plays a role in
      the cyclosporin A-induced nephrotoxicity, but the involvement of ET in the FK506
      induced renal dysfunction is still poorly understood. We elicited nephrotoxicity
      by daily administration of FK506 in spontaneously hypertensive rats, and we
      examined the renal gene expression of ET and its receptors and the effects of an
      ET receptor antagonist on FK506-induced renal dysfunction. FK506 administration
      (4 mg/kg/day, i.m.) for 14 days induced nephrotoxicity, including a renal
      vasoconstriction and a decrease in glomerular filtration rate. The renal
      dysfunction was accompanied by an increase in ET-1 mRNA levels, while ET(B)
      receptor mRNA was unaffected. Continuous administration of an ET(A)/ET(B)
      antagonist, TAK-044 (3 mg/day, s.c.), which effectively blocked systemic and
      renal vascular responses to exogenously administered ET-1, partially attenuated
      the FK506-induced renal vasoconstriction. However the reduced glomerular
      filtration rate were not affected by TAK-044. Thus, although enhanced gene
      expression of ET-1 in the kidney is involved in the renal vasoconstriction, ET
      does not play a major role in the FK506-induced renal dysfunction.

PMID- 9517404
TI  - Pulmonary edema induced by angiotensin I in rats.
AB  - This study was performed to demonstrate an experimental procedure of pulmonary
      edema induced by angiotensin I (AT I) in rats and to elucidate the mechanism of
      hemodynamic pulmonary edema. In the previous pilot study, 20 microg/kg of AT I
      was found to be an adequate dose for inducing pulmonary edema. To elucidate the
      mechanism of AT I pulmonary edema and protective measures against it, we observed
      the effects of captopril (CAP, 5 and 10 mg/kg), an angiotensin converting enzyme
      inhibitor; losartan (LOS, 10 mg/kg), an angiotensin II (AT II)-receptor
      antagonist; and phentolamine (PHE, 10 mg/kg), an alpha-adrenergic receptor
      blocker, on AT I-induced pulmonary edema in rats. Similarly, we also observed the
      effects of CAP (10 and 20 mg/kg) on pulmonary edema induced by 25 microg/kg of
      adrenaline (ADR) in rats. The development of AT I-induced pulmonary edema was
      significantly suppressed by CAP and LOS, but was unaffected by PHE. In contrast,
      the development of ADR-induced pulmonary edema was not suppressed by CAP. These
      results suggest that AT I-induced pulmonary edema is developed via the AT II and
      a specific AT II-receptor, without the indirect action of adrenaline.

PMID- 9517405
TI  - Cicletanine-induced decreases in cytosolic Ca2+ level and contraction in vascular
      smooth muscle.
AB  - The mechanism by which cicletanine (3-(4-chlorophenyl)-1,3-dihydro-7-hydroxy-6
      methylfuro-[3,4-c]pyri dine) induces vasodilatation was examined in isolated
      vascular smooth muscle. Cicletanine inhibited the contraction induced by high K+,
      norepinephrine (NE) and prostaglandin F2alpha in a concentration-dependent manner
      in rat aorta. High K+ (15.8-72.7 mM) elicited elevation of cytosolic Ca2+ level
      ([Ca2+]i) and contraction in a concentration-dependent manner. Cicletanine (300
      microM) inhibited the high K+-induced contractions without changing the
      [Ca2+]i/tension relationship. NE (3-300 nM) elicited greater contractions than
      high K+ at a given [Ca2+]i, suggesting that NE increased Ca2+ sensitivity of the
      contractile elements. Cicletanine inhibited the NE-induced contractions without
      changing the slope of the [Ca2+]i/tension relationship. Cicletanine inhibited the
      transient increases in both [Ca2+]i and muscle tension elicited by NE but not the
      transient increase in [Ca2+]i elicited by caffeine in Ca2+-free solution.
      Cicletanine did not inhibit contraction induced by Ca2+ in the permeabilized
      rabbit mesenteric artery with alpha-toxin. These results suggest that cicletanine
      inhibits vascular smooth muscle contraction by multiple mechanisms: 1) inhibition
      of Ca2+ influx via voltage-dependent Ca2+ channel and 2) inhibition of Ca2+
      release mediated by the alpha-adrenoceptors, but not by caffeine.

PMID- 9517406
TI  - Cardioprotective effects of KR-30450, a novel K+(ATP) opener, and its major
      metabolite KR-30818 on isolated rat hearts.
AB  - The cardiac effects of KR-30450 ((-)-(2R)-2-([1,3]-dioxolan-2-yl)-2-methyl-4-(2
      oxopyrrolidin++ +-1-yl)-6-nitro-2H-1-benzopyran), a newly synthesized potassium
      channel activator, and its major metabolite KR-30818 ((-)-(2R)-2-hydroxymethyl-2
      methyl-4-(2-oxopyrrolidin-1-yl)-6-nitr o-2H-1-benzopyran) were compared with
      those of lemakalim, a prototype of this class, in isolated globally ischemic rat
      hearts. KR-30450 and KR-30818 significantly improved reperfusion cardiac function
      (LVDP, left ventricular developed pressure; double product, LVDP x heart
      rate/1000), their potency being 5.2-fold and 0.7-fold greater than lemakalim
      (ED50 for recovering predrug double product: 0.10, 0.80 and 0.54 microM,
      respectively). KR-30450 and KR-30818 significantly attenuated reperfusion
      contracture and lactate dehydrogenase release with potency greater than and equal
      to lemakalim, respectively. They significantly increased time to contracture
      (TTC) during ischemia in a dose-dependent manner with a greater potency than
      lemakalim (EC25 for increasing TTC: 1.2, 2.1 and 3.2 microM, respectively). The
      protective effects of three compounds on the measured parameters were reversed by
      glyburide, a selective K+(ATP) blocker. In non-ischemic hearts, KR-30450 and
      lemakalim exerted weak negative inotropism at high concentrations and KR-30818
      had no effects, whereas the three compounds significantly increased coronary flow
      at doses studied. Glyburide completely reversed preischemic cardiodepressant
      effects of these compounds but not their effects on coronary flow. In conclusion,
      KR-30450, a recently developed K+(ATP) opener, exerted more potent
      cardioprotective effects than lemakalim, and its major metabolite KR-30818 may
      play a significant role in its action in vivo.

PMID- 9517408
TI  - Protection against glutamate neurotoxicity in retinal cultures by acidic
      conditions.
AB  - We evaluated the effects of extracellular acidic conditions on glutamate-induced
      death in cultured retinal neurons. Primary retinal cultures, obtained from 3- to
      5-day-old Wistar rats, were estimated to be consisted of mainly amacrine cells
      (90%) together with a small population of horizontal (8%) and ganglion cells
      (2%). We examined the effects of acidic pH (pH 6.0 to 7.0) on glutamate
      neurotoxicity by monitoring the delayed death of retinal neurons induced by brief
      (10 min) exposure to 1 mM glutamate followed by a 24-hr incubation. The glutamate
      induced delayed death of cultured retinal neurons was attenuated with an acidic
      pH between 6.0 and 7.0. Furthermore, whole-cell patch-clamp recordings were taken
      from retinal neurons to examine the effects of acidic pH on N-methyl-D-aspartate
      (NMDA) or kainate receptor-mediated currents. NMDA- and kainate-induced currents
      were suppressed at pH 6.0 to 7.0 and pH 6.0 to 6.5, respectively. The acidity of
      the medium protected the retinal neurons from glutamate-induced delayed death,
      probably by inhibiting NMDA and/or kainate receptor activation.

PMID- 9517407
TI  - Anti-inflammatory, analgesic and anti-pyretic effects of d-2-[4-(3-methyl-2
      thienyl)phenyl]propionic acid (M-5011), a new non-steroidal anti-inflammatory
      drug, in rats and guinea pigs.
AB  - Anti-inflammatory, analgesic and anti-pyretic effects of d-2-[4-(3-methyl-2
      thienyl)phenyl]propionic acid (M-5011), a new non-steroidal anti-inflammatory
      drug (NSAID), were compared with those of indomethacin, diclofenac sodium and
      ketoprofen in rats and guinea pigs. Anti-inflammatory effect of M-5011 on
      ultraviolet-induced erythema in guinea pigs was 11.7 and 1.8 times more potent
      than that of indomethacin and ketoprofen, respectively. Inhibitory effect of M
      5011 on carrageenin-induced paw edema was 2 and 1.5 times more potent than that
      of indomethacin and diclofenac sodium, respectively. Analgesic effect of M-5011
      on dry yeast-induced hyperalgesia or adjuvant-induced arthritic pain was
      equipotent to that of indomethacin, diclofenac sodium or ketoprofen. Anti-pyretic
      effect of M-5011 on yeast-induced pyrexia in rats was 4.2 and 4.6 times more
      potent than that of indomethacin and ketoprofen, respectively. Inhibitory effect
      of M-5011 on prostaglandin E2 production in the exudate of air-pouch inflammation
      induced by carrageenin was 1.75 times more potent than that in the non-inflamed
      site (stomach). As a result, gastric ulcerogenic activity of M-5011 was half that
      of indomethacin in rat. These results suggest that M-5011 shows more potent anti
      inflammatory and anti-pyretic effects and equipotent analgesic effect with low
      gastro-ulcerogenic activity compared with classical NSAIDs.

PMID- 9517409
TI  - Induction of tumor necrosis factor-alpha mRNA in the kidney of the mouse chronic
      hepatitis model.
AB  - Previously we reported the induction of tumor necrosis factor (TNF)-alpha mRNA in
      the liver of interferon (IFN)-gamma transgenic mouse, which might be the result
      of IFN-gamma gene expression. In the present study, IFN-gamma mRNA was induced in
      the liver, kidney and lung. TNF-alpha mRNA was, however, induced in the liver and
      kidney, but not in the lung. Induction of interleukin (IL)-2 and IL-1beta mRNA
      was lacking in any of these organs. The present result showed the induction of
      TNF-alpha mRNA expression in the kidney of transgenic mouse.

PMID- 9517411
TI  - The AMPA-receptor antagonist YM90K reduces AMPA receptor-mediated excitotoxicity
      in rat hippocampal cultures.
AB  - The effects of YM90K on alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid
      (AMPA) receptor-mediated excitotoxicity were investigated using kainate, AMPA and
      cyclothiazide in rat hippocampal cultures. YM90K had neuroprotective actions
      against both kainate toxicity and cyclothiazide-enhanced AMPA toxicity. YM90K
      induced a parallel and rightward shift of both kainate and AMPA dose-response
      curves. The application of YM90K even 3 hr after the start of kainate exposure
      significantly reduced kainate toxicity. These results indicate that YM90K
      protects neurons against AMPA receptor-mediated toxicity at an agonist site on
      the AMPA receptor and that YM90K protects against AMPA receptor-mediated toxicity
      even if applied after neurotoxic insult.

PMID- 9517410
TI  - Diverse relaxation responses of canine large and small conductive coronary
      arteries to glyceryl trinitrate and nitric oxide on the one hand and to 8
      bromoguanosine 3':5' cyclic monophosphate on the other.
AB  - Glyceryl trinitrate (GTN) and nitric oxide (NO) preferentially relaxed the large
      (2 mm in diameter) conductive coronary artery (CCA) of the dog, while 8
      bromoguanosine 3':5' cyclic monophosphate preferentially relaxed the small one
      (0.6 mm in diameter). Neither L-cysteine nor L-acetylcysteine affected GTN
      induced relaxation in small- and large-CCA. These results indicate that not
      different biotransformation of GTN to NO, but a process or processes operative
      between activation of guanylate cyclase and that of cyclic GMP-dependent protein
      kinase seems to be responsible for the preferential dilatation of large-CCA.

PMID- 9517412
TI  - Effect of muscarinic agonist on overflow incontinence induced by bilateral pelvic
      nerve transection in rats.
AB  - The effect of bethanechol, a muscarinic agonist, was studied by cystometrography
      in conscious rats with bilateral pelvic nerve (PN) lesions. In sham-operated
      rats, the transvesical infusion of saline elicited regularly micturition. The
      micturition was abolished by the bilateral PN transection, resulting in overflow
      incontinence. Bethanechol (30 mg/kg), administered orally to denervated rats,
      significantly increased the micturition frequency. Therefore, the micturition
      seems to be largely dependent upon muscarinic receptors of the bladder, and the
      finding supports the clinical effect of bethanechol. Moreover, this animal model
      may be useful for studying the overflow incontinence from detrusor failure of
      neuropathic origin.

PMID- 9517413
TI  - The powerful stimulatory action of 6-O-acetyl-9-methyl-7-bromoeudistomin D on the
      contractile protein system of rabbit skeletal muscle.
AB  - 6-O-Acetyl-9-methyl-7-bromoeudistomin D (AMBED) (> 10[-6] M), a derivative of
      eudistomin D, markedly enhanced the superprecipitation and the ATPase activity of
      skeletal muscle myosin B. In both the superprecipitation and ATPase activity of
      myosin B, the concentration-response curve for Ca2+ was shifted upwards by AMBED.
      AMBED did not affect the Ca2+-, K+-EDTA- or Mg2+-ATPase of myosin or the ATPase
      of actomyosin reconstituted from actin and myosin. These results suggest that
      AMBED causes an increase in the actomyosin ATPase activity mediated through the
      elevation of the maximum response to Ca2+, resulting in enhancement of the
      superprecipitation of skeletal muscle myosin B.

PMID- 9517414
TI  - Two distinct effects of 12S-hydroxyeicosatetraenoic acid on platelet aggregation
      by zooxanthellatoxin-A and ionomycin.
AB  - The marine toxin zooxanthellatoxin-A (ZT-A) and the Ca2+ ionophore ionomycin
      caused aggregation in rabbit platelets. While ZT-A-induced platelet aggregation
      was inhibited by indomethacin, ionomycin-induced aggregation was potentiated by
      the drug. In contrast, both ZT-A- and ionomycin-induced accumulations of
      thromboxane B2 (TXB2), a stable metabolite of thromboxane A2 (TXA2), were
      completely inhibited by indomethacin. 12S-Hydroxyeicosatetraenoic acid (12-HETE),
      which could be accumulated in the presence of indomethacin, inhibited ZT-A
      induced aggregation, but it potentiated the ionomycin-induced one. These results
      suggest that the different effects of indomethacin may be attributed to the
      distinct effects of 12-HETE on ZT-A- and ionomycin-induced platelet aggregations.

PMID- 9517415
TI  - Effect of growth factor on GTPase-activating protein (Ras GAP) in Chinese hamster
      ovary cells.
AB  - GTPase-activating proteins (GAPs) stimulate the hydrolysis of GTP bound to small
      G-proteins and regulate the signal transduction pathway. Changes in the
      expression of p21-Ras p120-GAP induced by growth factor treatment were examined
      in cultured Chinese hamster ovary (CHO) and human choriocarcinoma (BeWo) cells.
      Expression of p120-GAP and GAP activity were measured. Fetal bovine serum induced
      a significant increased level of GAP in CHO cells, but did not increase GAP in
      BeWo cells. The results suggest that growth factors affect Ras GAP expression in
      CHO cells, while they do not in other cells such as BeWo cells.

PMID- 9517416
TI  - Relationship between hippocampal theta-wave frequency and emotional behaviors in
      rabbits produced with stresses or psychotropic drugs.
AB  - The hippocampal EEG power spectra of rabbits were analyzed to clarify the
      relationship between the theta-wave and emotionality. The relative power of T2
      (6.0-7.9 Hz)/T1 (4.0-5.9 Hz) represented the index of theta-wave change.
      Emotional excitement (produced with novelty stress or methamphetamine) or
      suppression (produced with restraint stress or reserpine) increased or decreased
      T2/T1 ratios within around +/- 1 Hz changes. Furthermore, the imaging patterns of
      the peak feature make possible detailed characterization of emotional states.
      These results suggest that the hippocampus finely adjusts the theta-wave on a +/-
      1 Hz level, with a fine balance of voltage, in response to the emotional
      activity.

PMID- 9517417
TI  - The synaptic activation of the GluR5 subtype of kainate receptor in area CA3 of
      the rat hippocampus.
AB  - Two new compounds (LY293558 and LY294486), that antagonize homomeric human GluR5
      receptors, were examined against responses mediated by kainate receptors in the
      CA3 region of rat hippocampal slices. Both compounds (applied at a concentration
      of 10 microM) antagonized reversibly currents induced by 200 nM kainate. They
      also antagonized reversibly the synaptic activation of kainate receptors, evoked
      by high-frequency stimulation of mossy fibres, in the presence of NMDA and AMPA
      receptor antagonists. These results show that GluR5 subunits are likely to
      contribute to a kainate receptor on CA3 neurones that mediates responses to both
      kainate and synaptically-released L-glutamate.

PMID- 9517418
TI  - A novel kainate receptor ligand [3H]-(2S,4R)-4-methylglutamate: pharmacological
      characterization in rabbit brain membranes.
AB  - Since kainate evokes large non-desensitizing currents at alpha-amino-3-hydroxy-5
      methyl-4-isoxazolepropionic acid (AMPA) receptors, kainate is of limited use in
      discriminating between AMPA and kainate receptors. Following recent reports that
      (2S,4R)-4-methylglutamate is a kainate receptor-selective agonist, we have
      radiolabelled and subsequently characterized the binding of [3H]-(2S,4R)-4
      methylglutamate to rabbit whole-brain membranes. [3H]-(2S,4R)-4-methylglutamate
      binding was rapid, reversible and labelled two sites (KD1 = 3.67+/-0.50 nM/Bmax1
      = 0.54+/-0.03 pmol/mg protein and KD2 = 281.66+/-12.33 nM/ Bmax2 = 1.77+/-0.09
      pmol/mg protein). [3H]-(2S,4R)-4-methylglutamate binding was displaced by several
      non-NMDA receptor ligands: domoate > kainate >> L-quisqualate > or = L-glutamate
      > 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) >> (S)-AMPA = (S)-5
      fluorowillardiine > NMDA. Neither the metabotropic glutamate receptor agonists
      (1S,3R)-ACPD or L-AP4, together with the L-glutamate uptake inhibitor L-trans-2,4
      PDC, influenced binding when tested at 100 microM. We conclude that [3H]-(2S,4R)
      4-methylglutamate is a useful radioligand for labelling kainate receptors. It
      possesses high selectivity, and possesses a pharmacology similar to that for rat
      cloned low-affinity (Glu5 and 6) kainate receptor subunits.

PMID- 9517419
TI  - Pharmacological differentiation between neuronal and recombinant glutamate
      receptor channels expressed in Xenopus oocytes.
AB  - To determine the molecular components of neuronal glutamate receptors, it is
      important to identify pharmacological tools that allow differentiation between
      different glutamate receptor types. Here, we utilized the naphthalene derivative
      Evans Blue (EB) and a collection of other subtype-specific compounds (polyamine
      toxins, concanavalin A, cyclothiazide) to compare the pharmacological profile of
      neuronal and recombinant glutamate receptors GluR1-GluR6 expressed in Xenopus
      oocytes. Submicromolar concentrations of EB selectively reduced the activity of
      homomeric glutamate receptors GluR1, GluR2(Q) and GluR4. Applied at
      concentrations above 100 microM, EB potentiated kainate responses of receptors
      GluR1, GluR3 and GluR4, while receptors GluR2(Q) and GluR6(Q) were completely
      blocked. Similar experiments were performed on identified neurones in brain
      slices and after injection of rat brain RNA in Xenopus oocytes. Neuronal kainate
      responses were (i) potentiated by 100 microM cyclothiazide, (ii) slightly blocked
      after preincubation in 10 microM concanavalin A, and (iii) not significantly
      affected by either low (< 1 microM) or high (> 100 microM) concentrations of EB.
      Their pharmacological properties were markedly different from those of
      recombinant glutamate receptor channels GluR1-GluR6 investigated in heterologous
      expression systems.

PMID- 9517420
TI  - AMPA- and kainate-receptors differentially mediate excitatory amino acid-induced
      dopamine and acetylcholine release from rat striatal slices.
AB  - Rat striatal slices, preincubated with [3H]dopamine (DA) and [14C]choline, were
      superfused continuously. Detection of radioactivity was used to monitor the
      release of the neurotransmitters DA and acetylcholine (ACh). 6-Cyano-7
      nitroquinoxaline-2,3-dione (CNQX) and 2,3-dihydroxy-6-nitro-7
      sulfamoylbenzo(f)quinoxaline (NBQX) caused a concentration-dependent decrease in
      100 microM alpha-amino-3-hydroxy-5-methylisoxazol-4-propionate (AMPA)-, 100
      microM kainate- or 100 mM glutamate-induced release of DA and ACh. The IC50 of
      NBQX is 3-fold higher (for ACh release) and is 2-fold lower (for DA release) than
      that of CNQX. This is in agreement with the IC50 ratio of NBQX and CNQX on
      kainate- and AMPA-receptor binding. These two antagonists, at doses that produce
      an equivalent blockade of kainate-receptor binding (5 microM for NBQX and 1.56
      microM for CNQX), caused an approximately equal decrease in ACh- but not DA
      release induced by 100 microM kainate or AMPA. At doses that produce an
      equivalent blockade of AMPA-receptor binding (5 microM for NBQX and 10 microM for
      CNQX), they caused an approximately equal decrease in DA but not ACh release
      induced by 100 microM AMPA or kainate. Moreover, concanavalin A (0.3 and 0.5
      mg/ml), which selectively potentiates kainate-receptor responses, markedly
      enhanced 100 microM kainate-induced release of ACh but not DA. Cyclothiazide (10
      microM), which selectively potentiates AMPA-receptor responses, significantly
      increased 100 microM AMPA- or kainate-induced release of DA but not ACh. In
      summary, these results indicate that AMPA-and kainate-receptor activation,
      respectively, are predominantly involved in excitatory amino acid (EAA)-induced
      DA and ACh release in the striatum.

PMID- 9517421
TI  - LY354740: a metabotropic glutamate receptor agonist which ameliorates symptoms of
      nicotine withdrawal in rats.
AB  - LY354740 is a conformationally constrained analog of glutamate with high
      selectivity and nanomolar agonist activity at Group II metabotropic glutamate
      receptors (mGluRs). This orally active compound is a new drug candidate which is
      being developed for the treatment of anxiety. In this study, LY354740 was
      investigated in a model of nicotine withdrawal using the acoustic startle reflex
      (sensorimotor reactivity) in rats. Nicotine (6 mg/kg/day) was administered for 12
      days subcutaneously by osmotic minipumps. After 12 days the pumps were removed
      and the animals were allowed to go through spontaneous withdrawal. Cessation of
      chronic nicotine exposure led to increased startle responding for 4 days
      following withdrawal. Treatment with LY354740 (0.0001-0.1 mg/kg, i.p.; 0.03-3
      mg/kg, oral) produced a dose-dependent attenuation of the enhanced auditory
      startle responding following withdrawal of nicotine with intraperitoneal and oral
      ED50 values of 0.003 mg/kg and 0.7 mg/kg, respectively. These effects were
      stereoselective since the (-)-enantiomer of LY354740, LY366563, was without
      effect in this model. LY354740 produced no changes in the sensorimotor reactivity
      of rats not exposed to nicotine at oral doses up to 10 mg/kg. These data support
      the functional role of mGluR agonists in nicotine withdrawal and indicate that
      LY354740 may be efficacious in reducing the symptoms associated with nicotine
      withdrawal during smoking cessation in humans.

PMID- 9517422
TI  - The group I mGlu receptor agonist DHPG induces a novel form of LTD in the CA1
      region of the hippocampus.
AB  - The group I specific metabotropic glutamate (mGlu) receptor agonist (RS)-3,5
      dihydroxyphenylglycine (DHPG) (100 microM, 10 min) induced long-term depression
      (LTD) of synaptic transmission in the CA1 region of adult rat hippocampal slices,
      measured using a grease-gap recording technique. In "normal" (1 mM Mg2+
      containing) medium, LTD (measured 30 min after washout of DHPG) was small (13+/
      3%), but LTD was enhanced if DHPG was applied when the tissue was made
      hyperexcitable, either by omitting Mg2+ from the perfusate (35+/-3%) or by adding
      the GABA(A) receptor antagonist picrotoxin (29+/-2%). The N-methyl-D-aspartate
      (NMDA) receptor antagonist AP5 (100 microM) substantially reduced the generation
      of DHPG-induced LTD in Mg2+-free medium, but had little effect on LTD induced in
      the presence of picrotoxin. In Mg2+-free medium, the threshold concentration of
      DHPG required to induce LTD was between 1 and 3 microM. Neither agonists specific
      for group II (100 nM DCG-IV or 1 microM LY354740) or group III (10 microM L-AP4)
      mGlu receptors or a combined group I and II agonist (30-100 microM (1S,3R)-ACPD)
      induced LTD. However, an agonist (1 mM CHPG) which activates mGlu5 but not mGlu1
      receptors did induce LTD. Surprisingly, DHPG-induced LTD was reversed by mGlu
      receptor antagonists, applied hours after washout of DHPG. DHPG-induced LTD did
      not occlude with LTD induced by synaptic activation (1200 stimuli delivered at 2
      Hz), in Mg2+-free medium. These data show that activation of group I mGlu
      receptors (probably mGlu5) can induce LTD and that this mGlu receptor-mediated
      LTD may, or may not, require activation of NMDA receptors, depending on the
      experimental conditions.

PMID- 9517423
TI  - Group 1 metabotropic glutamate receptors contribute to slow-onset potentiation in
      the rat CA1 region in vivo.
AB  - It has been demonstrated in the CA1 region of the hippocampus in vitro, and in
      the dentate gyrus and CA1 region in vivo, that application of the metabotropic
      glutamate receptor (mGluR) agonist, 1S, 3R-amino cyclopentane 2,3-dicarboxylic
      acid triggers a slow-onset potentiation of synaptic transmission in the
      hippocampus. This study examined the involvement of group 1 and 2 mGluRs in this
      phenomenon in the CA1 region of freely moving rats. Drugs were applied via the
      lateral cerebral ventricle, and measurements were obtained from the CA1 region
      via permanently implanted electrodes. The group 1 mGluR agonists, 3,5
      dihydroxyphenylglycine (DHPG, 20-100 nmol/5 microl) and trans-azetidine-2,4
      dicarboxylic acid (ADA, 100 nmol-1 micromol/5 microl) induced a dose-dependent
      potentiation of basal synaptic transmission. The mGluR antagonist R,S-alpha
      methyl-carboxyphenylglycine (MCPG, 1 micromol), and the group 1 mGluR antagonist,
      S-4-carboxyphenylglycine (4CPG, 100 nmol) completely inhibited the effects of
      both DHPG and ADA. The group 2 mGluR agonist, (S)-4-carboxy-3-hydroxy
      phenylglycine (4C3H-PG, 50-200 nmol/5 microl) induced a dose-dependent decrease
      of basal synaptic transmission. These results suggest that in the CA1 region in
      vivo, slow-onset potentiation may be mediated by group 1 mGluRs.

PMID- 9517424
TI  - Long-term increase of hippocampal excitability by histamine and cyclic AMP.
AB  - The action of histamine (HA) on rat hippocampal CA1 pyramidal cells in vitro was
      investigated in slices perfused with solution containing 0.2 mM Ca2+/4.0 mM Mg2+.
      Extracellular recordings of the spontaneous discharges occurring under these
      conditions revealed that HA caused a long-lasting increase in cell firing. The HA
      effects were dose-dependent, in that low concentrations of HA (0.1-0.5 microM)
      exhibited an initial transient depression of cell firing and practically no long
      lasting action, whereas higher concentrations of HA (1-10 microM) exerted strong,
      non-declining increases. The H1-receptor antagonist mepyramine (1 microM) blocked
      the initial depression of firing and attenuated the long-lasting HA-mediated
      excitation. Pure H1-receptor activation, tested with the H1-receptor agonist 2-(3
      fluorphenyl)histamine (1-10 microM) depressed cell firing, similar to the low
      dose effects of HA. HA-induced excitations were prevented by the H2-receptor
      antagonist cimetidine (10-50 microM), and mimicked by the very potent H2-receptor
      agonist impromidine (1 or 3 microM) which was, however, less effective compared
      to equal concentrations of HA. H3-receptor activation by R-alpha-methylhistamine
      had no significant effect on cell firing. Thus, histamine H1 and H2 receptors
      seem to cooperate in producing this long-lasting augmentation of excitability. 8
      Bromo-cyclic AMP monophosphate (8-Br-cAMP, 50-100 microM) mimicked the long-term
      excitation, whereas the adenylyl-cyclase inhibitor 9-tetrahydro-2-furyladenine
      (THFA, 100-500 microM) or the PKA-inhibitor Rp-adenosine-3'5'-cyclic
      monophosphate (Rp-cAMPS, 10 microM) blocked it, indicating that the HA-mediated
      increase of excitability in the hippocampus is dependent on the adenylate
      cyclase/PKA-signal transduction cascade. DL-2-Amino-5-phosphonopentanoic acid
      (APV, 50 microM) significantly attenuated the magnitude of the HA-induced
      enhancement, indicating an NMDA receptor-dependent component. Other biogenic
      amines, acting through receptors positively coupled to adenylyl cyclase, elicited
      similar responses as HA, indicating common mechanisms by which these substances
      modulate excitability in CA1 pyramidal cells.

PMID- 9517425
TI  - Altered long-term potentiation in the young and old Ts65Dn mouse, a model for
      Down Syndrome.
AB  - We investigated the phenomenon of long-term potentiation (LTP) in a genetic model
      of Down Syndrome, the segmental trisomy mouse (Ts65Dn). Ts65Dn mice survive to
      adulthood and have an extra chromosome that contains a segment of chromosome 16
      homologous to human chromosome 21. In this study, field excitatory postsynaptic
      potentials (fEPSP) were recorded from the CA1 area of in vitro hippocampal slices
      from diploid and Ts65Dn mice, and LTP was induced by a single tetanizing pulse
      train (1 sec in duration) at 100 Hz. The hippocampus from both young (2 months)
      and older (9 months) Ts65Dn mice had a reduced LTP over a period of 60 min
      compared with LTP in age-matched controls. This finding may explain the reported
      behavioral and learning impairments in Ts65Dn mice; it suggests that this mouse
      model can be used to study the role of altered synaptic plasticity in mental
      retardation of Down Syndrome.

PMID- 9517426
TI  - High potency of the orally-active NMDA-receptor antagonist CGP 40 116 in
      inhibiting excitatory postsynaptic potentials of rat basolateral amygdala
      neurones in vitro.
AB  - Conventional intracellular recordings were used to monitor postsynaptic
      potentials of basolateral amygdala neurones (BLA) in brain slices comprising the
      BLA, the entorhinal cortex (EC) and the hippocampus, in which the EC-BLA
      connections were preserved. Stimulation of the BLA with a bipolar electrode
      elicited complex postsynaptic potentials consisting of alpha-amino-3-hydroxy-5
      methyl-isoxazoleproprionic acid (AMPA) receptor-mediated fast excitatory
      postsynaptic potentials (fast EPSPs), gamma-amino-butyric acid [GABA(A)] receptor
      mediated fast inhibitory postsynaptic potentials (fast IPSPs) and GABAB receptor
      mediated slow IPSPs. Bath application of 10 microM of the AMPA receptor
      antagonist 6-cyano-7-nitroquinoxaline-2,3-dione and of 10 microM of the GABA(A)
      receptor antagonist bicuculline methiodide (BMI) revealed a N-methyl-D-aspartate
      (NMDA) receptor-mediated slow EPSPs, which was occasionally followed by a GABAB
      receptor-mediated slow IPSPs. Under these conditions, the log concentration
      response curve for D-(E)-2-amino-4-methyl-5-phosphono-3-pentanoic acid (CGP 40
      116), a newly developed drug with proposed NMDA-receptor antagonist properties,
      was compared to that obtained with the 'classic' antagonist D(-)-2-amino-5
      phosphonopentanoic acid (D-AP5) in inhibiting the NMDA-mediated postsynaptic
      potentials. CGP 40 116 (IC50: 130 nM) was over 30 times more potent than D-AP5
      (IC50: 4100 nM) in reducing NMDA-mediated slow EPSP. In conclusion, the present
      study indicates that CGP 40 116, a new orally-active NMDA antagonist, shows a
      very high potency on NMDA receptors in the amygdala and may therefore be a
      valuable tool for studying the behavioural effect of NMDA-receptor mediated
      transmission in this structure.

PMID- 9517428
TI  - Endogenous nitric oxide facilitates striatal dopamine and glutamate efflux in
      vivo: role of ionotropic glutamate receptor-dependent mechanisms.
AB  - We have investigated the influence of the nitric oxide synthase (NOS) substrate,
      NG-hydroxy-L-arginine (H-ARG) on dopamine (DA) and glutamate (GLU) efflux in vivo
      using concentric microdialysis probes implanted in the anterior-medial striatum
      of chloral hydrate-anesthetized rats. Intrastriatal infusion of H-ARG (100
      microM, 200 microM, or 1 mM for 120 min) increased DA efflux in a dose-dependent
      fashion. The facilitatory effect of H-ARG (1 mM) on DA efflux was abolished
      following pretreatment (80 min) with the constitutive NOS inhibitor 7
      nitroindazole (7-NI, 10 microM) but unaffected by L-NG(1-iminoethyl) lysine (100
      microM) infusion. As both H-ARG (1 mM) and the NO-generator (+/-)-S-nitroso-N
      acetylpenicillamine (1 mM) were observed to increase GLU efflux concurrently with
      the effect on DA efflux, we evaluated the potential intermediary role of GLU in
      NO-facilitated DA efflux using ionotropic GLU receptor antagonists. Local
      infusion of dizocilpine maleate (10 microM) or (+/-)-2-amino-3-[3
      (carboxymethoxy)-5-methyl-isoxazol-4-yl] propionic acid (100 microM), attenuated
      the H-ARG (1 mM)-induced elevation of extracellular DA levels. Conversely,
      similar treatment with the kainate receptor antagonist d-gamma-glutamyl
      aminomethanesulfonic acid did not alter H-ARG-induced DA efflux. To evaluate the
      regulatory influence of striatal NO on NMDA receptor activation, NMDA (100
      microM) was co-perfused with either H-ARG (2 mM) or 7-NI (10 microM). While co
      perfusion with 7-NI potentiated NMDA-induced DA efflux, similar treatment with H
      ARG (2 mM) abolished the effect. These results demonstrate that endogenous NO
      production, stimulated via H-ARG-dependent activation of type 1 NOS, enhances
      striatal DA efflux via an increase in glutamatergic tone on ionotropic GLU
      receptors. At higher levels of NOS activation (following H-ARG (2 mM) or NMDA
      infusion), NO may block glutamatergic neurotransmission via inhibition of NMDA
      receptor function.

PMID- 9517427
TI  - Pharmacological characterization of N-methyl-D-aspartate receptors in spinal cord
      of rats with a chronic peripheral mononeuropathy.
AB  - N-Methyl-D-aspartate (NMDA) receptor antagonists, acting in the spinal cord, are
      analgesic. However, the clinical utility of these antagonists is diminished by
      their adverse effects on cognition and behavior. To facilitate the development of
      spinal cord-selective NMDA receptor antagonists, we characterized ligand
      interactions at NMDA receptors in spinal cord of normal rats and rats with a
      chronic peripheral neuropathy. NMDA receptors in spinal cord were distinguished
      from those in cerebral cortex on the basis of differences in the potencies of
      competitive and noncompetitive antagonists and on the basis of differences in
      their response to spermidine. D(-)-2-Amino-5-phosphonopentanoic acid (AP-5) and
      (+)-(1-hydroxy-3-aminopyrrolidine-2-one) (HA-966) were more potent in inhibiting
      NMDA-dependent [3H]TCP binding in spinal cord while, conversely, MK-801 was more
      potent in inhibiting [3H]TCP binding to NMDA receptors in cerebral cortex.
      Spermidine increased [3H]TCP binding to NMDA receptors in cerebral cortex (39+/
      8%) but not spinal cord (2+/-1%). Based on these properties, NMDA receptors in
      spinal cord more closely resembled those in cerebellum than those in cerebral
      cortex. Generation of a chronic neuropathy had no effect on the density of NMDA
      receptors in lumbar spinal cord. There were also no major changes in the
      potencies of competitive antagonists or channel blocking ligands, although there
      was a trend for kynurenic acid and D-CPP to be more potent in the spinal cords of
      neuropathic animals. These findings indicate that, in both normal and neuropathic
      pain states, NMDA receptors in spinal cord can be distinguished pharmacologically
      from those in cerebral cortex. These findings underscore the feasibility of
      developing spinal cord-selective NMDA receptor antagonists as novel analgesics.

PMID- 9517429
TI  - The role of nitric oxide in passive avoidance learning.
AB  - The role of nitric oxide on passive avoidance learning was studied by
      administering L-arginine or D-arginine to male rats in a passive avoidance
      paradigm. L-Arginine administered into the lateral brain ventricle at a dose of
      1.25 microg showed a tendency to increase the passive avoidance latency, and 2.5
      microg exerted almost maximal action, but the action gradually increased still
      further up to 20 microg tested. D-Arginine had no action. Peripheral
      administration (intraperitoneal) of L-arginine facilitated the consolidation of
      passive avoidance learning in a dose-dependent manner. A significant increase in
      passive avoidance response was obtained following an injection of 100 mg/kg L
      arginine. When L-arginine was given i.c.v. with a selected dose of 5 microg, 30
      min prior to a learning trial, the latency of the passive avoidance response was
      likewise lengthened. However, when L-arginine was given 30 min before the 24-hr
      testing (retrieval), it was ineffective. It was also ineffective when given 6 hr
      after the training trial. However, when L-arginine was administered immediately
      following the training trial, the action in improving the consolidation could be
      detected 6 hr after the training trial. Nitro-L-arginine, which blocks nitric
      oxide synthase, can also block the facilitation of consolidation caused by the
      nitric oxide donor L-arginine. The nitric oxide synthase inhibitor per se in
      different doses had no action on the learning of a passive avoidance task. The
      results indicate that nitric oxide is able to facilitate the learning and
      consolidation of memory in a passive avoidance paradigm, but it is ineffective in
      retrieval processes. The results also suggest that, under the experimental
      circumstances used, nitric oxide is involved only in the facilitated learning and
      memory processes caused by pharmacological effect of L-arginine, and not involved
      in normal learning processes.

PMID- 9517430
TI  - Dynamic changes in NADPH-diaphorase staining reflect activity of nitric oxide
      synthase: evidence for a dopaminergic regulation of striatal nitric oxide
      release.
AB  - In fixed tissue, neuronal NADPH-diaphorase staining results from nitric oxide
      synthase (NOS) activity. Neuronal NOS only synthesizes nitric oxide once
      activated by the binding of Ca2+/calmodulin. We show here that neuronal NADPH
      diaphorase staining is also dependent on Ca2+/calmodulin, implying that only
      activated NOS is detected. In addition, in bovine pulmonary endothelial cells,
      carbachol and bradykinin dramatically and rapidly increase the intensity of NADPH
      diaphorase staining. Furthermore, administration of MK801, an NMDA antagonist,
      decreases neuronal NADPH-diaphorase staining. This suggests that the intensity of
      the NADPH-diaphorase staining is related to the level of enzyme activation at the
      moment of tissue fixation. The potential of exploiting this observation to detect
      cellular activation of NOS is illustrated by the observations that the intensity
      of NADPH-diaphorase staining in rat striatal neurones is decreased following
      systemic treatment with the D1-like dopamine receptor antagonist SCH23390, and
      increased by the D2-like antagonist eticlopride. These results therefore provide
      strong evidence that the NADPH-diaphorase reaction can be used to monitor NOS
      activity at a cellular level of resolution, and reveal a dopaminergic regulation
      of NOS activity in the striatum mediated by D1-like and D2-like dopamine
      receptors.

PMID- 9517431
TI  - Functional properties of recombinant GABA(A) receptors composed of single or
      multiple beta subunit subtypes.
AB  - GABA(A) receptor (GABAR) isoforms in the central nervous system are composed of
      combinations of alpha(1-6), beta(1-4), gamma(1-4), delta(1) and epsilon(1)
      subunit subtypes arranged in a pentamer. Many regions of the brain express high
      levels of mRNA encoding several different subunits and even multiple subunit
      subtypes. The stoichiometry of GABAR isoforms is unclear, and the number and
      identity of individual subunit subtypes that are coassembled remain uncertain. To
      examine the role of beta subunit subtypes in the functional properties of GABARS
      and to determine whether multiple beta subtypes can be coassembled in functional
      GABARs, plasmids containing cDNAs encoding rat beta1 and/or beta3, alpha5 and
      gamma2L subtypes were cotransfected into L929 fibroblasts. The properties of the
      expressed receptor populations were determined using whole-cell and single
      channel recording techniques. The alpha5beta1gamma2L isoform was less sensitive
      to GABA than the alpha5beta3gamma2L isoform. alpha5beta1gamma2L isoform currents
      were also insensitive to the allosteric modulator loreclezole, while
      alpha5beta3gamma2L isoform currents were strongly potentiated by loreclezole.
      Fibroblasts transfected with plasmids containing cDNAs for both beta1 and beta3
      subtypes along with alpha5 and gamma2L subtypes produced a receptor population
      with an intermediate sensitivity to GABA which was insensitive to loreclezole.
      These results suggest that functional GABARs can be formed that contain two
      different beta1 subunit subtypes with properties different from receptors that
      contain only a single beta1 subtype and that the beta1 subunit subtypes influence
      the response of GABARs to GABA and to the allosteric modulator loreclezole.

PMID- 9517432
TI  - The role of the GABA(A) receptor alpha1 subunit N-terminal extracellular domain
      in propofol potentiation of chloride current.
AB  - Propofol (2,6-diisopropylphenol), an intravenous general anesthetic in active
      clinical use today, potentiates the action of gamma-aminobutyric acid (GABA) at
      the type-A receptor and also directly induces current in the absence of GABA. We
      expressed different combinations of murine GABA(A) receptor alpha1, beta3 and
      gamma2 subunits in Xenopus oocytes to investigate the subunit dependence of
      propofol potentiation of pentobarbital-induced current. Pentobarbital induces
      current in all beta3-subunit-containing receptors, whereas current gating by GABA
      requires the presence of both alpha1 and beta3 subunits. Therefore, pentobarbital
      rather than GABA was used to induce current in order to separate the subunit
      dependence of current gating from the subunit dependence of potentiating action
      of propofol. alpha1beta3gamma2, alpha1beta3, beta3gamma2, or beta3 subunit
      combinations all responded to pentobarbital in a dose-dependent manner. True
      potentiation was defined as the current magnitude to simultaneous application of
      pentobarbital and propofol exceeding the additive responses to individual drug
      applications. A dose-dependent propofol potentiation of pentobarbital-induced
      current was observed in oocytes injected with alpha1beta3 or alpha1beta3gamma2
      but not in beta3gamma2 or beta3 subunits, suggesting that the alpha1 subunit was
      necessary for this modulatory action of propofol. Further examination of the
      propofol potentiation in chimeras between the alpha1 and beta3 subunits showed
      that the extracellular amino-terminal half of the alpha1 subunit was sufficient
      to support propofol potentiation. The different requirements of the receptor
      structure for the agonistic (gating) and the potentiating actions suggest that
      these two actions of propofol are distinct processes mediated through its action
      at distinct sites.

PMID- 9517433
TI  - The role of G proteins in the activity and mercury modulation of GABA-induced
      currents in rat neurons.
AB  - The role of G proteins in the functional modulation and potentiation by mercury
      chloride of the GABA(A) receptor-channel complex in rat dorsal root ganglion
      neurons was studied by using the whole-cell patch clamp technique. Stimulation of
      Gs proteins by application of GTP-gamma-S in the patch pipette or by incubation
      of neurons with cholera toxin reduced GABA-induced currents, suggesting
      modulation of GABA-induced currents via a Gs-protein-coupled pathway. GDP-beta-S
      in the pipette solution or pretreatment of dorsal root ganglion neurons with
      pertussis toxin suppressed GABA-induced currents, suggesting that basal Gi/Go
      protein activity positively modulates the GABA(A) receptor-channel complex.
      Mercury chloride potentiation of GABA-activated currents was blocked by
      application of GTP-gamma-S in the patch pipette or by incubation of neurons with
      cholera toxin. Mercury chloride potentiation of GABA-activated currents was
      blocked by application of GDP-beta-S in the patch pipette or by incubation of
      neurons with pertussis toxin. G proteins, probably Gi/Go proteins, underlie the
      mercury chloride potentiation of GABA-induced currents.

PMID- 9517434
TI  - The role of phosphorylation in the activity and mercury modulation of GABA
      induced currents in rat neurons.
AB  - The role of protein kinase A (PKA) and protein kinase C (PKC) in the function and
      modulation by mercury chloride of the GABA(A) receptor-chloride channel complex
      was studied with rat dorsal root ganglion cells using the whole-cell patch clamp
      technique. When added to the internal pipette solutions, both KT 5720, a
      selective PKA inhibitor, and calphostin C, a selective PKC inhibitor, increased
      the maximal current and shifted the EC50 for GABA in the direction of higher GABA
      concentrations. GABA-activated currents were decreased by the addition of 5 mM
      cAMP to the internal pipette solution, and by external perfusion of 100 nM
      phorbol 13-myristate 13-acetate. Mercury chloride potentiation of GABA-activated
      currents was blocked by internal application of 5 mM cAMP. PKA in the recording
      pipette abolished the mercury chloride potentiation of GABA-activated currents.
      In contrast, 0.56 microM KT 5720, but not calphostin C, in the internal pipette
      solution enhanced the effect of mercury chloride. In conclusion, both PKA and PKC
      negatively regulate the activity of the GABA(A) receptor-channel complex probably
      through phosphorylation of the receptor, and the PKA system underlies the
      mechanism of mercury chloride potentiation of GABA-activated currents.

PMID- 9517435
TI  - Action of zolpidem on responses to GABA in relation to mRNAs for GABA(A) receptor
      alpha subunits within single cells: evidence for multiple functional GABA(A)
      isoreceptors on individual neurons.
AB  - The relationship between zolpidem sensitivity and GABA(A) receptor alpha subunits
      was studied in individual dissociated neurons from rat brain. Using whole-cell
      recording, similar EC50 values were demonstrated for the effect of gamma
      aminobutyric acid (GABA) on gated-chloride currents from substantia nigra
      reticulata (SNR) and lateral septal neurons. Subsequently, many neurons from both
      the SNR or lateral septum were found to exhibit enhanced GABA-gated chloride
      currents across concentrations of zolpidem ranging from 10 to 300 nM. Some
      neurons exhibited a greater than 20% increase in responsiveness to GABA at 30 nM
      of zolpidem without further increase at higher concentrations of zolpidem.
      Conversely, zolpidem enhancement of GABA from another group of neurons was not
      observed at 30 nM zolpidem, but between 100 and 300 nM the response to GABA
      increased greater than 20%. Finally, a third group of neurons reached both of
      these criteria for zolpidem enhancement of GABA. This latter spectrum of
      responses to GABA after varying concentrations of zolpidem was consistent with
      the presence of either two GABA(A) receptors or a single receptor with differing
      affinities for zolpidem on an individual neuron. Following determination of the
      sensitivity of neurons from SNR or lateral septum to zolpidem, cytoplasm was
      extracted from some individual cells to allow identification of cellular mRNAs
      for the alpha1, alpha2 and alpha3 GABA(A) receptor subunits with RT-PCR. Those
      neurons that responded to the 30 nM zolpidem concentration invariably expressed
      the alpha1-GABA(A) receptor subunit. This result is consistent with the GABA(A)
      alpha1-receptor subunit being an integral part of a functional high-affinity
      zolpidem type 1-BZD receptor complex on neurons in brain. Those neurons which
      showed enhancement of GABA from 100 to 300 nM zolpidem contained mRNAs for the
      alpha2 and/or the alpha3 receptor subunits, a finding consistent with these alpha
      subunits forming type 2-BZD receptors. Some individual dissociated SNR neurons
      were sensitive to both low and high concentrations of zolpidem and contained
      mRNAs for all three alpha-receptor subunits. These latter individual neurons are
      proposed to have at least two functional GABA(A) receptor subtypes. Thus, the
      present investigation emphasizes the importance of characterizing the
      relationship between endogenous GABA(A) receptor function and the presence of
      specific structural components forming GABA(A) receptor subtypes on neurons.

PMID- 9517436
TI  - Evidence for a non-GABAergic action of quaternary salts of bicuculline on
      dopaminergic neurones.
AB  - Intracellular recordings were made from neurones, presumed to be dopaminergic, in
      the rat midbrain slice preparation. Bicuculline methiodide (BMI) and
      methochloride (BMC) reversibly blocked the slow, apamin-sensitive component of
      the afterhyperpolarization in these cells. The IC50 for this effect was about 26
      microM. In comparison, BMC antagonized the input resistance decrease evoked by
      muscimol (3 microM) with an IC50 of 7 microM. The base of bicuculline was less
      potent in blocking the slow afterhyperpolarization. SR95531 (2-[carboxy-3'
      propyl]-3-amino-6-paramethoxy-phenyl-pyridaziniu m bromide), another competitive
      GABA(A) antagonist, and picrotoxin, a non-competitive GABA(A) antagonist, also
      blocked the action of muscimol (IC50s: 2 and 12 microM respectively), but had no
      effect on the afterhyperpolarization at a concentration of up to 100 microM.
      Moreover, 100 microM SR95531 did not affect the blockade of the
      afterhyperpolarization by BMC. This blockade persisted in the presence of
      tetrodotoxin and was apparently not due to a reduction of calcium entry,
      suggesting that it involved a direct action on the channels which mediate this
      afterhyperpolarization. These results strongly suggest that quaternary salts of
      bicuculline act on more than one target in the central nervous system. Thus, the
      involvement of GABA(A) receptors in a given effect cannot be proven solely on the
      basis of its blockade by these agents.

PMID- 9517437
TI  - Mechanisms underlying the antidopaminergic effect of clonazepam and melatonin in
      striatum.
AB  - Intrastriatal injection of the GABA(A) antagonist, bicuculline, caused about a
      75% decrease in the inhibitory effect of the central-type benzodiazepine (BZ)
      agonist, clonazepam or the indoleamine hormone, melatonin, on apomorphine-induced
      rotation in a 6-hydroxydopamine model of dopaminergic supersensitivity.
      Pretreatment with the peripheral-type BZ antagonist, PK 11195 (intrastriatally or
      intraperitoneally), also attenuated the antidopaminergic effect of these drugs
      but with much less potency than bicuculline. However, the combination of both
      bicuculline and PK 11195, injected directly into the striatum, completely blocked
      the antidopaminergic action of clonazepam or melatonin. These results indicate
      that the antidopaminergic action of clonazepam and melatonin in the striatum
      involves two distinct mechanisms: (1) a predominant GABAergic activation via the
      BZ/GABA(A) receptor complex, and (2) a secondary mechanism linked to a PK 11195
      sensitive BZ receptor pathway. Recent studies indicate that PK 11195 blocks BZ
      induced inhibition of the adenylyl cyclase-cyclic AMP pathway in the striatum.
      Since cyclic AMP has been implicated in the rotational behaviour of 6
      hydroxydopamine-lesioned animals, it is possible that the antidopaminergic action
      of clonazepam and melatonin also involves suppression of this second messenger.

PMID- 9517438
TI  - Normalization of cytochrome-c oxidase activity in the rat brain by neuroleptics
      after chronic treatment with PCP or methamphetamine.
AB  - Previous studies, primarily involving the use of positron emission tomography
      (PET), have contributed to the hypothesis that a state of hypometabolism may
      underlie schizophrenia. The chronic use of methamphetamine (MAP) or phencyclidine
      (PCP), both of which have been shown to enhance dopaminergic function in the
      brain, leads to a psychotic state in man which has prompted the suggestion that
      these compounds may have utility as models of schizophrenia. In the present
      study, regional alterations in energy metabolism were examined in the rat brain
      using cytochrome-c oxidase (COX) and succinate dehydrogenase (SDH) histochemistry
      following chronic treatment with PCP and MAP. PCP and MAP were administered alone
      or in the presence of fluphenazine or clozapine to animals for 28 days, after
      which mitochondrial enzyme activities were estimated. Both PCP and MAP produced
      profoundly similar decreases in COX activity in a broad spectrum of regions. Most
      prominent in this regard were the caudate-putamen, nucleus accumbens and septum.
      No changes were noted in sections stained for SDH activity, suggesting that
      results were dependent upon neither a generalized mitochondrial dysfunction nor
      mitochondrial loss. Cell counts and TUNEL histochemistry also failed to reveal
      any significant differences between control and treated animals, implying that
      reductions were not a result of cell loss. Both clozapine and fluphenazine
      offered varying degrees of protection from the effects of PCP and MAP. The
      results provide evidence which implicates dopaminergic hyperactivity in the
      finding of reduced energy metabolism in the brains of schizophrenics.

PMID- 9517439
TI  - The effects of CCK-4 on dopamine D1 agonist-induced grooming are blocked by a
      CCK(A) receptor antagonist: evidence for a novel CCK receptor subtype?
AB  - The neuropeptide cholecystokinin (CCK) has been shown to interact with dopamine
      in various ways, including attenuation of dopamine D1 receptor-mediated vacuous
      chewing and grooming. While we have demonstrated a clear role for the CCK(A)
      receptor in the attenuation of dopamine D1 agonist-induced vacuous chewing,
      studies of grooming yielded anomalous results. We examined the effects of
      selective CCK receptor antagonists on the attenuation of SKF 38393-induced
      grooming by the CCKB agonist CCK-4. Administration of SKF 38393 (5 mg/kg s.c.) to
      male Sprague-Dawley rats resulted in a significant increase in grooming which was
      reduced to control levels by CCK-4 (20 mg/kg i.p.). Pretreatment with either the
      CCKA receptor antagonist devazepide or the CCK(B) receptor antagonist L-365,260
      significantly attenuated this effect over a range of doses (20, 100, 500
      microg/kg i.p.). The suppression of dopamine D1 agonist-induced grooming by CCK-4
      does not appear to reflect a non-specific effect of anxiogenesis, as it was
      unaffected by the anxiolytic diazepam. The CCK receptor antagonists alone were
      without behavioural effect. Taken together with previous studies in models of
      anxiety and analgesia, our findings lend further support to the hypothesis that
      CCK-4 may act at a novel receptor subtype.

PMID- 9517440
TI  - Antipsychotic regulation of dopamine D1, D2 and D3 receptor mRNA.
AB  - A range of antipsychotic drugs, both "typical" and "atypical", was administered
      to rats over a time course and at several different dosages. The mRNA levels of
      dopamine D1, D2 and D3 receptor were measured in either whole brain or dissected
      brain regions. D3 receptor mRNA was up-regulated in whole brain by clozapine (10
      and 30 but not 3 mg/kg/day), sulpiride (50 and 100 but not 20 mg/kg/day).
      haloperidol (3 but not 1 or 0.3 mg/kg/day), flupenthixol (3 but not 1 or 0.3
      mg/kg/day), pimozide (4.5 but not 1.5 or 0.5 mg/kg/day) and loxapine (1.2 and 4
      mg/kg/day but not 0.4 mg/kg/day). Sulpiride (100 mg/kg/day), clozapine (30 mg/kg/
      day) and haloperidol (3 mg/kg/day) all up-regulated the D3 receptor mRNA in
      nucleus accumbens and olfactory tubercles but not striatum. D1 and D2 receptor
      mRNA was up-regulated in whole brain by haloperidol and loxapine only, and in the
      case of haloperidol this was localized to striatum and prefrontal cortex.
      Haloperidol, clozapine and sulpiride all down-regulated D1 mRNA in hippocampus
      and additionally haloperidol and sulpiride down-regulated it in the cerebellum.
      This work shows that all the drugs tested up-regulated D3 receptor, but effects
      on D1 and D2 receptors were less general.

PMID- 9517441
TI  - Acute effects of 3,4-methylenedioxymethamphetamine (MDMA) on 5-HT cell firing and
      release: comparison between dorsal and median raphe 5-HT systems.
AB  - It is proposed that 3,4-methylenedioxymethamphetamine (MDMA; Ecstasy) is more
      toxic to 5-HT neurones projecting from the dorsal raphe nucleus (DRN) than to
      those from the median raphe nucleus (MRN). Since increased 5-HT release has been
      associated with MDMA-induced neurotoxicity, MDMA may have a DRN-selective 5-HT
      releasing effect. Here we have compared the effects of acute MDMA on DRN and MRN
      5-HT pathways using in vivo electrophysiological and neurochemical techniques.
      MDMA inhibited the firing of 5-HT neurones in both the DRN and the MRN, and did
      so with similar potency (ED50 values, 0.589 +/- 0.151 (8) and 0.588 +/- 0.207 (6)
      mg/kg i.v., respectively). In both nuclei this inhibitory effect was reversed by
      the selective 5-HT1A receptor antagonist, WAY 100635 (0.1 mg/kg i.v.).
      Microdialysis measurements were made in the frontal cortex and dorsal
      hippocampus, regions which receive a DRN- and an MRN-selective 5-HT innervation,
      respectively. A dose of 1 mg/kg i.v. MDMA increased extracellular 5-HT 3-fold in
      both the frontal cortex and dorsal hippocampus. A higher dose (3 mg/kg i.v.)
      increased 5-HT levels 8-fold in both regions. Overall, our data suggest that MDMA
      releases 5-HT from the cell body and terminal regions of both DRN and MRN 5-HT
      pathways, and does so in a qualitatively and quantitatively similar fashion. We
      conclude that any DRN-selectivity in the neurotoxic effects of MDMA is not due to
      a DRN-selective, acute 5-HT releasing action of the drug.

PMID- 9517442
TI  - Serotonin inhibits epileptiform discharge by activation of 5-HT1A receptors in
      CA1 pyramidal neurons.
AB  - The anti-epileptiform effect of serotonin was characterized in cellular models of
      epilepsy using electrophysiological recording techniques. In the bicuculline
      model, both serotonin (20 microM) and its 5-HT1A agonist, 8-hydroxy-2-(di-n
      propylamino)tetralin (8-OH-DPAT, 10 microM) completely blocked the epileptiform
      discharge and caused membrane hyperpolarization and reduction in input
      resistance. These effects were completely antagonized by the 5-HT1A receptor
      antagonist N-t-butyl-3(4-[2-methoxyphenyl]piperazin-1-yl)-2-phenyl-propanamid
      e(WAY 100135) (10 microM). Epileptiform discharge induced by positive current
      injection was also blocked by serotonin. The presence of WAY 100135 renders
      serotonin ineffective in the same model. In the bicuculline model, epileptiform
      discharge blocked by serotonin reappeared and was also intensified when BaCl2 was
      added to the medium. To rule out the possibility of serotonin-induced
      hyperpolarization strengthening the inhibitory effect of endogenous Mg2+ on
      glutamate N-methyl-D-aspartic acid (NMDA) receptor we studied the antiepileptic
      effect of serotonin in the 0 Mg2+ model. Spontaneous activity and evoked bursts
      seen with the 0 Mg2+ model were completely blocked by serotonin. WAY 100135
      completely antagonized serotonin effects in this model as well. This study
      provides evidence suggesting that in rat CA1 pyramidal neurons, serotonin can
      inhibit epileptiform activity in a variety of accepted epilepsy cellular models
      and that inhibition of epileptiform bursts by serotonin may be mediated by
      activation of the 5-HT1A receptor subtype.

PMID- 9517443
TI  - 5-HT autoreceptors in the regulation of 5-HT release from guinea pig raphe
      nucleus and hypothalamus.
AB  - 5-HT autoreceptors involved in the regulation of 5-HT release in the guinea pig
      dorsal raphe nucleus have been studied in comparison with those in the
      hypothalamus. In vitro release was measured in slices of raphe and hypothalamus
      prelabelled with [3H]5-HT, superfused with Krebs solution and depolarized
      electrically. The non-selective 5-HT receptor agonist, 5-carboxamidotryptamine (5
      CT) (0.1-10 nM for raphe: 1-100 nM for hypothalamus) and antagonist, methiothepin
      (10-1000nM), decreased and increased, respectively, the release of [3H]5-HT
      evoked by electrical stimulation in either of these regions when given alone. The
      selective 5-HT1B/D receptor antagonist, GR127935 (100-1000 nM), and the 5-HT1D
      receptor antagonist, ketanserin (300-1000 nM), had no significant effect on this
      release in either of these regions. Methiothepin and GR127935 (100-1000 nM)
      shifted to the right the concentration-effect curve of 5-CT in both the raphe and
      the hypothalamus. At 300 nM, ketanserin shifted to the right the concentration
      effect curve of 5-CT in the raphe but did not modify the 5-CT curve in the
      hypothalamus. In microdialysis experiments ketanserin, applied locally at 10
      microM, increased the extracellular levels of 5-HT in the dorsal raphe nucleus of
      the freely moving guinea pig, whereas 5-HT levels were unchanged in the
      hypothalamus. Ketanserin at 1 microM did not affect the decrease in 5-HT output
      induced by the selective 5-HT1B/D receptor agonist, naratriptan (used at 10
      microM in raphe and 0.1 microM in hypothalamus), in the raphe or the
      hypothalamus. In the raphe, WAY100635, a 5-HT1A receptor antagonist, at 1 microM,
      did not prevent naratriptan (10 microM) from reducing the extracellular levels of
      5-HT. These results suggest that, in the conditions used in this study, the
      release of 5-HT in the dorsal raphe nucleus is possibly modulated in part by 5
      HT1B receptors but essentially the control is through 5-HT receptors whose
      subtype is still to be determined. In the hypothalamus, however, it is clear that
      only 5-HT1B receptors are involved in the modulation of 5-HT neurotransmission.

PMID- 9517444
TI  - A single pretreatment with 8-OH-DPAT reduces behavioral indices of serotonin 1A
      receptor activation in ovariectomized rats.
AB  - The effects of prior treatment with 8-OH-DPAT on 8-OH-DPAT-induced eating
      behavior, hypothermia, flat body posture and forepaw treading were examined in
      ovariectomized rats. Twenty-four hours after a single pretreatment with 0.25
      mg/kg of the drug, the eating behavior and flat body posture induced by 8-OH-DPAT
      were reduced relative to that seen following the first treatment with the drug.
      In contrast, within 24 hr of the prior drug treatment, the drug's effects on
      forepaw treading and rectal temperature were unchanged. However, 7 days after
      prior treatment with 8-OH-DPAT, eating behavior, flat body posture and
      hypothermia induced by the drug were suppressed. Only forepaw treading remained
      unchanged. These findings are discussed in reference to similar studies of 5-HT1A
      receptor agonist-induced modulation of behaviors in male rats.

PMID- 9517445
TI  - MKC-242, a novel 5-HT1A receptor agonist, facilitates cortical acetylcholine
      release by a mechanism different from that of 8-OH-DPAT in awake rats.
AB  - We have previously reported that 5-?3-[((2S)-1,4-benzodioxan-2
      ylmethyl)amino]propoxy?-1,3-be nzodioxole (MKC-242), a potent and selective
      serotonin (5-HT)1A receptor agonist, exerts anxiolytic- and antidepressant-like
      effects in animal models and that the antidepressant-like effect may be mediated
      by postsynaptic 5-HT1A receptors. The present study, using a microdialysis
      technique, was undertaken to characterize in vivo the effect of MKC-242 on
      cholinergic neurons. Subcutaneous injection of MKC-242 (0.5-1.0 mg/kg), like the
      typical 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH
      DPAT), increased extracellular acetylcholine (ACh) levels in the rat cerebral
      cortex. The increase in ACh release by MKC-242 was also observed in the
      hippocampus. The effect of MKC-242 on cortical ACh release was attenuated by
      pretreatment with the 5-HT1A receptor antagonists (10 mg/kg, s.c.) propranolol
      and N-tert-butyl-3-(4-(2-methoxyphenyl)piperazin-1-yl)-2-phenylpropana mide. The
      increase in cortical ACh release by MKC-242 was blocked by lesion of serotonergic
      neurons with 5,7-dihydroxytryptamine, whereas that by 8-OH-DPAT was not. Lesion
      of noradrenergic neurons with N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine did
      not affect the MKC-242-induced increase in ACh release. These results suggest
      that systemic injection of MKC-242 facilitates in vivo ACh release via an
      activation of somadendritic 5-HT1A autoreceptors, and that MKC-242 and 8-OH-DPAT
      affect cholinergic neurons in the rat cerebral cortex via different mechanisms.

PMID- 9517446
TI  - Selectivity of hemicholinium mustard, an affinity ligand, for the high-affinity
      choline transport system.
AB  - The selectivity of the irreversible inhibition of high-affinity choline uptake
      (HACU) by hemicholinium mustard (HCM; 2,2'-(4,4'-biphenylene)bis[2-hydroxy-4-(2
      bromoethyl)-morpholine] hydrochloride) with respect to other cholinergic proteins
      and other sodium-dependent transport systems was examined. Preincubation of rat
      forebrain membranes with HCM, followed by washing and measurement of [3H]
      hemicholinium-3 binding to the high-affinity choline transporter, was shown to
      decrease binding capacity (Bmax) by 70% without affecting the apparent affinity
      of the ligand. However, a similar preincubation, wash and binding experiment
      using [3H]-NMS as a ligand for muscarinic receptors showed no HCM effect on
      binding parameters. To measure the effects of HCM on choline acetyltransferase
      (ChAT), synaptosomes were incubated in HCM, then washed. The synaptosomes were
      lysed and ChAT activity was measured. Treatment with 50 microM HCM, a
      concentration that inhibits 100% of synaptosomal HACU, results in a 24% decrease
      in ChAT activity. HCM demonstrates little residual inhibition of other sodium
      dependent neurotransmitter transporter transporters: preincubation with 50 microM
      HCM results in a decrease of 12% in transport of [3H]-dopamine and a decrease of
      6% in the transport of [3H]-GABA. The binding of HCM, like that of hemicholinium
      3 is sodium-dependent. HCM preincubation in the presence of sodium results in
      inhibition of HACU to 32% of control; in the absence of sodium HACU is 65% of
      control. This represents a loss of 51% of the observed irreversible inhibition
      produced by HCM. Irreversible inhibition by HCM can also be prevented by co
      incubation with hemicholinium-3. Co-incubation with hemicholinium-3 results in
      residual HACU inhibition that decreases from 51% (HCM alone) to 28% (HCM +
      hemicholinium-3). When atropine instead of hemicholinium-3 is co-incubated with
      HCM, HCM still inhibits 40% of transport, demonstrating the pharmacological
      specificity of the protective effect of hemicholinium-3. Experiments in the
      guinea-pig myenteric plexus preparation demonstrate a gradual recovery from the
      residual effects of HCM. Evoked ACh release decreases to 24% immediately
      following treatment with 1 microM HCM. After 2 hr of recovery, tissues have
      recovered to about 50% of control levels, after which recovery continues at a
      slower rate.

PMID- 9517448
TI  - Comparative effects of FK-506, rapamycin and cyclosporin A, on the in vitro
      differentiation of dorsal root ganglia explants and septal cholinergic neurons.
AB  - There is increasing evidence that immunophilins play a role in neural development
      and differentiation. We have studied the neurotrophic effects of FK-506,
      rapamycin and cyclosporin A (CsA) on dorsal root ganglia (DRG) taken from
      different segmental levels (cervical, thoracic and lumbar/sacral), and on rat
      embryonic septal cholinergic neurons in culture. At a low concentration (1 nM),
      FK-506 significantly increased (+83%) the number of neurites of thoracic DRG
      explants. At a higher concentration (100 nM), it also enhanced the neuritogenesis
      of thoracic (+100%) and lumbar/sacral (+57%) DRG, but not cervical DRG explants.
      Rapamycin displayed a converse effect, reducing the development of DRG explants
      from cervical and thoracic segments (-78% at 1 nM in thoracic DRG). CsA (from 1
      to 100 nM) was without effect on DRG neuritogenesis. In contrast to nerve growth
      factor (NGF), which increased neurite length (+116% at 3 ng/ml), neither FK-506
      nor rapamycin affected this parameter.

PMID- 9517447
TI  - Inhibition of M-current in cultured rat superior cervical ganglia by linopirdine:
      mechanism of action studies.
AB  - The mechanism involved in the blockade of M-current by linopirdine was studied in
      cultured rat superior cervical sympathetic ganglia using whole-cell patch clamp
      recording. The effects of modulators of intracellular signal transduction
      pathways on muscarine- or linopirdine-induced inhibition of M-current were
      compared. Intracellular addition of GDP-beta-S (500 microM) attenuated M-current
      block by muscarine (1 microM) but not that of linopirdine (10 microM).
      Intracellular dialysis of GTP-gamma)-S (100 microM) enhanced and prolonged
      muscarine-induced inhibition of M-current but had no effect on the activity of
      linopirdine. Intracellular BAPTA (20 mM) also inhibited the effects of muscarine
      without affecting those of linopirdine. Intracellular application of linopirdine
      had no effect on either basal M-current amplitude or the ability of linopirdine
      to block M-current when administered extracellularly. These results indicate that
      M-current inhibition by linopirdine is unlikely to be either G-protein-mediated
      or calcium-mediated or to involve an intracellular site of action and are,
      therefore, consistent with a direct block of the M-channel from its extracellular
      side.

PMID- 9517449
TI  - Modulation by calcium/calmodulin-dependent protein kinase II of functional
      response of delta opioid receptor in neuroblastoma x glioma hybrid (NG108-15)
      cells.
AB  - The potential modulation of opioid receptor signaling by calcium/calmodulin
      dependent protein kinase II (CaMKII) has been investigated in NG108-15 cells.
      Both CaMKII specific inhibitors used, KN62 and KN93, time- and dose-dependently
      blocked inhibition of cAMP accumulation by [D-Pen2, D-Pen5]enkephalin (DPDPE),
      with an IC50 of about 1.2 microM and 0.8 microM, respectively. In the presence of
      1 microM KN62 or KN93, the DPDPE dose-response curve shifted to the right (IC50
      from 0.7 to 20 nM for KN62 and from 0.65 to 10 nM for KN93, respectively), and
      the maximal response was also significantly reduced. KN92, an inactive analogue
      of KN93, showed no significant impact, while ionomycin, an activator of CaMKII,
      greatly potentiated the opioid receptor response, suggesting that the effects of
      KN62, KN93 and ionomycin were likely mediated through CaMKII. In addition, KN62
      did not affect ligand binding, receptor/Gi coupling, or basal and forskolin
      stimulated adenylyl cyclase activity, suggesting its possible interference in the
      Gi/adenylyl cyclase interaction. Furthermore, a CaMKII inhibitor potently blocked
      the functional responses of other Gi-coupled receptors (m4 muscarinic and alpha2
      adrenergic receptors) tested, but not that of Gs-coupled receptors (prostaglandin
      E1 and adenosine receptors). Our results clearly demonstrate that CaMKII
      modulates the signaling of opioid receptor and other Gi-coupled receptors.

PMID- 9517450
TI  - The natural beta-carbolines facilitate inositol phosphate accumulation by
      activating small G-proteins in human neuroblastoma cells (SH-SY5Y).
AB  - The naturally occurring beta-carbolines exert psychotropic actions in humans and
      have numerous behavioral effects in animals. The known in vitro activities of
      these substances do not provide a satisfactory explanation for their in vivo
      effects. The present study was undertaken to explore the possibility of a
      specific signal transduction pathway. The human neuroblastoma cell line SH-SY5Y
      was used as a model system. High-affinity binding sites for [3H]norharman
      (synonymous: beta-carboline) were detected. Pharmacological characterization
      revealed displacement of the ligand by beta-carbolines, to a weaker extent by
      indoleamines, but not by opioids, muscarinic receptor agonists, metabotropic
      glutamate receptor agonists or several peptide neurotransmitters. Inositol
      phosphate accumulation was only slightly affected by the beta-carbolines.
      However, the action of carbachol was clearly facilitated in a dose-dependent and
      pertussis toxin-insensitive manner. Pretreatment of the cells with Clostridium
      difficile toxin B blocked the facilitating effect of the beta-carbolines by
      concentrations which did not affect the action of carbachol alone. This suggests
      that low molecular weight GTP-binding proteins are involved in the facilitating
      action of the beta-carbolines. This mechanism was further supported by
      experiments measuring the concentrations of phosphatidylinositol phosphates after
      various activating compounds. In conclusion, the facilitating effect of beta
      carbolines on inositol phosphate accumulation could play a part in the actions of
      beta-carbolines and may be produced by stimulating the generation of
      phosphatidylinositol-4,5-bisphosphate (PtdIns-4,5-P2), the key component in the
      activation of phosphoinositide-phospholipase C.

PMID- 9517451
TI  - Effects of anesthetics on Fos protein expression in autonomic brain nuclei
      related to cardiovascular regulation.
AB  - We tested the influence of urethane, chloral hydrate and a mixture of
      ketamine/xylazine on Fos protein expression in autonomic brain regions related to
      blood pressure. We conclude that ketamine/xylazine is a suitable anesthetic to be
      used in studies looking at c-fos expression in neural circuits serving
      cardiovascular regulation.

PMID- 9517452
TI  - Short term effect of steroids on catecholamine secretion from bovine adrenal
      medulla chromaffin cells.
AB  - Bovine chromaffin cells were used to examine neuronal modulation, as their
      function is similar to sympathetic post-ganglionic neurons. The effect of
      steroids on evoked catecholamine secretion from primary culture of bovine adrenal
      medullary cells was investigated. A wide range of progestins, androgens and
      estrogens was found to have a significant effect on catecholamine secretion
      induced by the natural neurotransmitter acetylcholine (ACh). The androgens
      (especially androstandione and androsterone), as a class were the most effective
      in inhibition of stimulated secretion, while the estrogens had little, to no,
      effect. Among all steroids tested, progesterone had the most significant effect,
      other progestins were less potent. Progesterone inhibited catecholamine secretion
      evoked by ACh, nicotine and oxotremorine-M in a dose-dependent manner with
      similar IC50 values in the microM range. It also blocked the secretion evoked by
      high potassium concentration (59 nM) or veratradine (100 microM), but no effect
      was seen on the secretion evoked by the calcium ionophore A-23187 (10 microM).
      Progesterone inhibition of ACh or oxotremorine-M stimulation was immediate and
      sustained. These results suggest that progesterone and other steroids might have
      a membrane effect probably acting through blockade of calcium influx necessary
      for the secretory response.

PMID- 9517453
TI  - Calcium-dependent release specificities of various cell lines loaded with
      different transmitters.
AB  - By loading cells in culture with acetylcholine (ACh) we have characterized a
      calcium-dependent release mechanism and shown that it was expressed independently
      of synthesis or storage of ACh. (Israel et al., 1994, Neurochemistry
      International 37, 1475-1483; Falk-Vairant et al., 1996a, Proc. Natl. Acad. Sci.
      U.S.A. 93, 5203-5207; Falk-Vairant et al., 1996b, Neuroscience 75, 353-360; Falk
      Vairant et al., 1996c, Journal of Neuroscience Research 45, 195-201). The
      transmitter loading procedure was applied to two other transmitters, gamma
      aminobutyric acid (GABA) and glutamate (Glu). We could then study the specificity
      of the release mechanism for the three transmitters in a variety of cell lines,
      including neural-derived cells. Four different calcium-dependent release
      phenotypes were identified: two were specific for ACh or GABA, and two co
      released two transmitters ACh and GABA but not Glu, or ACh and Glu but not GABA.
      We conclude that release mechanisms having different specificities are expressed
      by the cell lines studied, they become functional after loading the cells with
      the relevant transmitters. These observations will help the identification of
      proteins controlling the specificity of release, and provide an interesting model
      for pharmacological studies.

PMID- 9517454
TI  - Inhibition of human N-type voltage-gated Ca2+ channels by the neuroprotective
      agent BW619C89.
AB  - Human N-type Ca2+ channels were rapidly and reversibly inhibited by 5-100 microM
      BW619C89 (IC50 = 16.4 microM at Vtest = + 10 mV and Vhold = - 90 mV). In the
      presence of 20 microM BW619C89, activation kinetics were significantly faster.
      The degree of inhibition observed was affected by both test and holding
      potential, indicating state-dependent interactions with the N-type Ca2+ channel.

PMID- 9517455
TI  - Sustained neurotransmitter release: new molecular clues.
AB  - Chemical synapses convey impulses at high frequency by exocytosis of synaptic
      vesicles. To avoid failure of synaptic transmission, rapid replenishment of
      synaptic vesicles must occur. Recent molecular perturbation studies have
      confirmed that the recycling of synaptic vesicles involves clathrin-mediated
      endocytosis. The rate of exocytosis would thus be limited by the capacity of the
      synaptic clathrin machinery unless vesicles could be drawn from existing pools.
      The mobilization of vesicles from the pool clustered at the release sites appears
      to provide a mechanism by which the rate of exocytosis can intermittently exceed
      the rate of recycling. Perturbation of synapsins causes disruption of vesicle
      clusters and impairment of synaptic transmission at high but not at low
      frequencies. Both clathrin-mediated recycling and mobilization of vesicles from
      the reserve pool are thus important in the replenishment of synaptic vesicles.
      The efficacy of each mechanism appears to differ between synapses which operate
      with different patterns of activity.

PMID- 9517456
TI  - Cloning, chromosomal localization and functional expression of the gene encoding
      the alpha-subunit of the cGMP-gated channel in human cone photoreceptors.
AB  - Cyclic nucleotide-gated (CNG) ion channels serve as final targets of signal
      transduction in vertebrate photoreceptors. While the basic mechanisms of
      phototransduction are similar in rod and cone photoreceptors, both cell types
      express distinct sets of components of the transduction pathway. We report here
      the cloning of the cDNA encoding the alpha-subunit of the cGMP-gated channel of
      human cone photoreceptors. The open reading frame predicts a polypeptide of 694
      amino acid residues with conserved functional parts and amino acid positions
      typical for the alpha-subunit of CNG-channels. Heterologous expression of the
      cDNA in Xenopus oocytes gave rise to cGMP-gated channel activity. Antiserum
      directed against the C-terminus of the bovine cone CNG channel alpha-subunit
      crossreacted specifically with the heterologously expressed polypeptide and
      stained cone photoreceptors and weakly also the outer plexiform layer in human
      retinal sections. Northern blot analysis detected a prominent mRNA species of
      approximately 3.8 kb in human retina. The entire gene spans approximately 30 kb
      of genomic sequence and is located on the pericentric band q11.2 of human
      chromosome 2. The gene is composed of seven exons, with introns located at
      positions which are preserved with respect to the human rod gene, indicating a
      common ancestral gene structure. RT-PCR analysis gave no evidence for
      alternatively spliced transcripts.

PMID- 9517457
TI  - Neurotransmitter modulation of gap junctional communication in the rat
      hippocampus.
AB  - Increasing experimental evidence indicates that gap junctions can be modulated by
      neurotransmitters, in particular dopamine. To examine possible modulation of gap
      junctional communication in the rat hippocampus by neurotransmitters, we studied
      dye coupling and electrotonic transmission in the CA1 area in the presence of
      carbachol, a cholinergic agonist, and dopamine agonists. Carbachol markedly
      reduced dye coupling and the frequency of electrotonic potentials (spikelets).
      Spikelet amplitudes were decreased in the presence of carbachol. These effects
      were reversed by the cholinergic antagonist atropine, suggesting a muscarinic
      action of carbachol on gap junctional function. The non-specific dopamine agonist
      apomorphine, and the specific D1 receptor agonist SKF 38393, reduced dye coupling
      between pyramidal cells. Spikelet frequency was also decreased in the presence of
      dopamine agonists, but less than with carbachol. The specific D1 receptor
      antagonist, SCH 23390, reversed the effects of both dopamine agonists. These
      observations indicate that cholinergic and dopaminergic transmission can affect
      electrical and chemical (dye coupling) communication through gap junctions, and
      could therefore alter properties of neuronal assemblies, in addition to their
      effects on intrinsic membrane properties.

PMID- 9517458
TI  - Autoinhibition of supraoptic nucleus vasopressin neurons in vivo: a combined
      retrodialysis/electrophysiological study in rats.
AB  - To examine the role of endogenous vasopressin on the electrical activity of
      vasopressin neurons within the supraoptic nucleus of the rat brain in vivo, we
      have developed a novel technical approach for administering neuroactive drugs
      directly into the extracellular environment of the neuronal dendrites. A
      microdialysis probe was used for controlled local drug administration into the
      dendritic area of the nucleus during extracellular recording of single neurons in
      vivo. Vasopressin or selective V1 receptor antagonists were administered for
      between 10 and 30 min via a U-shaped microdialysis probe placed flat on the
      surface of the supraoptic nucleus after transpharyngeal exposure of the nucleus
      in urethane-anaesthetized rats. Microdialysis administration (retrodialysis) of
      vasopressin inhibited vasopressin neurons by reducing their firing rate,
      sometimes to total inactivity. Retrodialysis of V1-receptor antagonists partially
      reversed the effect of vasopressin, and a subsequent vasopressin administration
      was not effective in reducing the activity of these neurons, suggesting a
      receptor-mediated action of endogenous vasopressin. In addition, the duration of
      the periods of activity and the mean frequency during the active phase were
      increased in vasopressin neurons after retrodialysis of V1-receptor antagonist,
      indicating a physiological role of endogenous vasopressin. Neither vasopressin
      nor the antagonists altered the activity of continuously firing oxytocin neurons.
      Thus, vasopressin released within the supraoptic nucleus may act via V1 receptors
      located specifically on vasopressin neurons to regulate their phasic activity by
      an auto-inhibitory action. Since vasopressin release from the dendrites of
      vasopressin neurons is increased and prolonged after various forms of
      stimulation, it is proposed that this mechanism will act to limit excitation of
      vasopressin neurons, and hence secretion from the neurohypophysis. In addition,
      combined in vivo retrodialysis/ single cell recording allows controlled
      introduction of neuroactive substances into the extracellular fluid in the
      immediate vicinity of recorded neurons. This is shown to provide a novel approach
      to study neurotransmitter actions on supraoptic neurons in vivo.

PMID- 9517459
TI  - In vivo amygdala dopamine levels modulate cocaine self-administration behaviour
      in the rat: D1 dopamine receptor involvement.
AB  - Nucleus accumbens dopamine is often hypothesized as the critical factor for
      modulating cocaine self-administration. In the current study we examined the
      extent to which dopamine in the amygdala could contribute to cocaine intake
      behaviour and modify nucleus accumbens dopamine levels. Rats were trained to self
      administer intravenous cocaine (1.5 mg/kg/injection) under a fixed-ratio
      reinforcement schedule in daily 3 h operant training sessions. In the first in
      vivo microdialysis experiment, extracellular dopamine levels were found to be
      increased 200% of baseline in the amygdala and by 400% in the nucleus accumbens.
      Although cocaine induced similar profiles of dopamine overflow in the two
      mesolimbic areas, in the nucleus accumbens the latency of the dopaminergic
      response was shorter (three- to four-fold) during both initiation and termination
      of the cocaine self-administration session than in the amygdala. Despite
      achieving a stable self-regulated pattern of cocaine intake and high dopamine
      concentrations in the nucleus accumbens, a unilateral injection of the D1
      receptor antagonist SCH 23390 (0.5 or 1.5 microg) into the amygdala was still
      able to increase the rate of cocaine intake. This behavioural effect was
      accompanied by a dose-dependent increase in nucleus accumbens dopamine levels; at
      the highest SCH 23390 concentration cocaine intake was increased by 400% and
      dopamine levels were potentiated by an additional 400%. In vivo autoradiography
      using [3H]SCH 23390 showed that D1 receptor sites contributing to the behavioural
      and subsequent neurochemical effects were predominantly localized to the amygdala
      and not the nucleus accumbens. Altogether these results point to a significant
      contribution of in vivo amygdala D1 dopamine transmission to cocaine self
      administration behaviour.

PMID- 9517460
TI  - VEGF mRNA induction correlates with changes in the vascular architecture upon
      spinal cord damage in the rat.
AB  - The multiple cellular and molecular processes induced by injury to the central
      nervous system (CNS) are still poorly understood. In the present study, we
      investigated the response of the vasculature and the expression of mRNA for the
      angiogenic vascular endothelial growth factor (VEGF) following X-irradiation of
      the spinal cord in the newborn and following traumatic spinal cord injury in the
      adult rat. Both lesion models induced changes in the density and the distribution
      pattern of blood vessels: while X-irradiation led to a permanent local increase
      in vascular density in the fibre tracts of the exposed segments, a transient
      local sprouting of vessels was induced upon traumatic spinal cord injury. In situ
      hybridization showed that an increase of VEGF mRNA anticipated and overlapped
      with the vascular responses in both lesion models. In addition to the temporal
      correlation of VEGF expression and vascular sprouting, there was a clear
      correlation in the spatial distribution patterns. Following X-irradiation, the
      expression of VEGF mRNA was restricted to the fibre tracts, precisely the areas
      where the changes in the vasculature were observed later on. Upon transection in
      the adult animal, VEGF was mainly detectable at the border of the lesion area,
      where the transient increase in vascular density could be observed.
      Interestingly, according to the type of lesion applied, astrocytes (X
      irradiation) or inflammatory cells (presumably microglial cells or macrophages;
      traumatic lesion) are the cellular sources of VEGF mRNA. Our results strongly
      indicate that VEGF is crucially involved in mediating vascular changes following
      different types of injury in the CNS.

PMID- 9517461
TI  - Neurotrophins stimulate chemotaxis of embryonic cortical neurons.
AB  - During mammalian cortical development, neuronal precursors proliferate within
      ventricular regions then migrate to their target destinations in the cortical
      plate, where they organize into layers. In the rat, most cortical neuronal
      migration occurs during the final week of gestation (Bayer et al, 1991; Jacobson,
      1991). At this time (E15-E21), reverse transcriptase-polymerase chain reaction
      demonstrated that cortical homogenates contain mRNA encoding brain derived
      neurotrophic factor (BDNF) and the catalytic form of its high-affinity receptor,
      TrkB. Immunocytochemistry and in situ hybridization of sections revealed that the
      catalytic TrkB receptors predominantly localize to regions containing migratory
      cells. Many TrkB+ cells exhibited the classic morphology of migrating neurons,
      suggesting that TrkB ligands play a role in cortical neuronal migration. We
      analysed whether TrkB ligands influence the motility of embryonic cortical cells
      (from E15-E21) using a quantitative in vitro chemotaxis assay. High-affinity TrkB
      ligands (BDNF and NT4/5) stimulated chemotaxis (directed migration) of embryonic
      neurons at concentrations ranging from 1 to 100 ng/ml. NT-3, a low-affinity TrkB
      ligand, only stimulated significant migration at high concentrations (> or =100
      ng/ml). Peak migration to BDNF was observed at gestational day 18 (E18). BDNF
      induced chemotaxis was blocked by either tyrosine kinase inhibitor, K252a, or the
      Ca2+-chelator, BAPTA-AM, suggesting that BDNF-induces motility via
      autophosphorylation of TrkB receptor proteins and involves Ca2+-dependent
      mechanisms. BDNF-stimulation of increased cytosolic Ca2+ was confirmed with
      optical recordings of E18 cortical cells loaded with Ca2+ indicator dye. Thus,
      signal transduction through the TrkB receptor complex directs neuronal migration,
      suggesting that, in vivo, BDNF exerts chemotropic effects that are critical to
      morphogenesis of the cortex.

PMID- 9517462
TI  - Phenotype specification of cortical neurons during a period of molecular
      plasticity.
AB  - The transient expression of neuropeptide transmitters is a common feature of the
      developing cortex. We have now analysed the role of cortical afferents in shaping
      the neurochemical architecture of rat visual cortex using organotypic cultures.
      Deafferented cortex monocultures prepared from newborn rats reveal a constant NPY
      mRNA expression in 6-8% of all cortical neurons up to 90 days in vitro (DIV). In
      contrast, afferent thalamocortical and corticocortical axonal innervation elicits
      a progressive reduction in the percentage of NPY mRNA expressing neurons from
      initially 6-8% in 30DIV cocultures to 2-3% and 3-4% respectively in 60DIV
      cocultures, which is maintained for up to 90DIV. This phenotype restriction is
      not observed in only efferently connected corticocollicular cocultures. Further,
      axonal innervation does not change the percentage of GAD mRNA-expressing neurons,
      which remains at 13% in mono- and cocultures. When feeding thalamocortical
      cocultures with monoculture-conditioned medium between 3-20DIV followed by normal
      medium up to 60DIV, the phenotype restriction fails to occur in the cocultured
      cortex. We conclude that cortex-derived factors secreted into the medium by a
      monoculture suppress the phenotype-restricting capacity of the afferents, but
      only when present within the first 14DIV during the period of formation of axonal
      connections. To elucidate the nature of the cortex-derived factors, brain-derived
      neurotrophic factor was applied to the medium. When applied for the first 14DIV,
      it does not prevent the phenotype restriction from occurring. This suggests that
      epigenetic factors such as axonal innervation and cortex-derived factors other
      than brain-derived neurotrophic factor govern a phenotype decision in neocortical
      neurons during a period of molecular plasticity.

PMID- 9517463
TI  - Learning deficit in BDNF mutant mice.
AB  - Brain-derived neurotrophic factor (BDNF) has been implicated in the regulation of
      high-frequency synaptic transmission and long-term potentiation in the
      hippocampus, processes that are also thought to be involved in the learning of
      spatial tasks such as the Morris water maze. In order to determine whether BDNF
      is required for normal spatial learning, mice carrying a deletion in one copy of
      the BDNF gene were subjected to the Morris water maze task. Young adult BDNF
      mutant mice were significantly impaired compared with wild-type mice, requiring
      twice the number of days to reach full performance. Aged wild-type mice performed
      significantly worse than young wild-type mice and the effect was even more
      pronounced in the BDNF mutant mice, which did not learn at all. Although there
      was no difference in mean swimming speed between BDNF mutant and wild-type mice,
      we cannot exclude the possibility that developmental or peripheral deficits also
      contribute to the learning deficits in these mice. In situ hybridization and
      RNase protection analysis revealed that BDNF mRNA expression was indeed decreased
      in BDNF mutant mice. Furthermore, a pronounced effect of age on BDNF mRNA
      expression was seen, displayed as both a reduced level of mRNA expression and a
      reduced or entirely absent layer-specific expression pattern in the cerebral
      cortex of aged animals. Thus, our data suggest that BDNF expression may be linked
      to learning.

PMID- 9517464
TI  - Plateau potentials in cat neocortical association cells in vivo: synaptic control
      of dendritic excitability.
AB  - The dendrites of neocortical pyramidal cells are bombarded by myriads of synaptic
      inputs and express active conductances generating prominent plateau potentials.
      We have examined in vivo the possibility that spontaneous synaptic inputs trigger
      or terminate plateau potentials after blockage of K+ currents. Under barbiturate
      anaesthesia, pairs of cortical cells were intracellularly recorded with sharp
      electrodes from the cat's association cortex (areas 5-7). In one pyramidal cell,
      K+ channels were blocked with intracellular Cs+, while in the simultaneously
      impaled pyramidal cell the K+ conductances were left intact to act as a control;
      this second cell allowed recognition of spontaneous spindle-related synaptic
      activity. Depolarizing current pulses elicited single, all-or-none plateau
      potentials (60-70 mV, 0.1-0.4 s). Plateau potentials slowly repolarized towards a
      break point of fast repolarization around -20 mV. Thalamic-evoked inhibitory
      postsynaptic potentials consistently shut off the plateaus. Synchronized
      spontaneous activity, as occurring during thalamic-generated spindle
      oscillations, either triggered or blocked the plateaus. These results suggest
      that spontaneously occurring synaptic activation during synchronized oscillatory
      states, such as those that occur during sleep spindles in vivo, may exert a
      strong control over the dendritic excitability in neocortical pyramidal cells.

PMID- 9517465
TI  - HERG- and IRK-like inward rectifier currents are sequentially expressed during
      neuronal development of neural crest cells and their derivatives.
AB  - Quail neural crest cells were cultured in a differentiative medium to study the
      inward K+ channel profile in neuronal precursors at various stages of maturation.
      Between 12 and 24 h of culture, neural crest-derived neurons displayed, in
      addition to the previously described outward depolarization-activated K+
      currents, an inward current enhanced in high K+ medium. A biophysical and
      pharmacological analysis led us to conclude that this inward K+ current is
      identical to that previously demonstrated in mouse and human neuroblastoma cell
      lines (I[IR]). This current (quail I[IR] or ql[IR]), which is active at membrane
      potentials positive to -35 mV, was blocked by Cs+ and by class III antiarrhythmic
      drugs, thus resembling the K+ current encoded by the human ether-a-go-go-related
      gene (HERG). At later stages of incubation (>48 h), neural crest-derived neurons
      underwent morphological and biochemical differentiation and expressed fast Na+
      currents. At this stage the cells lost qI[IR], displaying instead a classical
      inward rectifier K+ (IRK) current (quail I[IRK] = qI[IRK]). This substitution was
      reflected in the resting potential (VREST), which became hyperpolarized by >20 mV
      compared with the 24 h cells. Neurons were also harvested from peripheral ganglia
      and other derivatives originating from the migration of neural crest cells, viz.
      ciliary ganglia, dorsal root ganglia, adrenal medulla and sympathetic chain
      ganglia. After brief culture following harvesting from young embryos, ganglionic
      neurons always expressed qI(IR). On the other hand, when ganglia were explanted
      from older embryos (7-12 days), briefly cultured neurons displayed the IRK-like
      current. Again, in all the above derivatives the qI(IR) substitution by qI(IRK)
      was accompanied by a 20 mV hyperpolarization of VREST. Together, these data
      indicate that the VREST of normal neuronal precursors is sequentially regulated
      by HERG- and IRK-like currents, suggesting that HERG-like channels mark an
      immature and transient stage of neuronal differentiation, probably the same stage
      frozen in neuroblastomas by neoplastic transformation.

PMID- 9517466
TI  - The oxytocin-induced inward current in vagal neurons of the rat is mediated by G
      protein activation but not by an increase in the intracellular calcium
      concentration.
AB  - The neuropeptide oxytocin can depolarize parasympathetic preganglionic neurons in
      the dorsal motor nucleus of the vagus nerve of the rat by generating a sustained
      inward current, which is sodium-dependent and tetrodotoxin-insensitive. The
      second messenger activated by oxytocin receptor binding is, however, not yet
      known. In the present study, we attempted to characterize it by using the whole
      cell recording technique and brainstem slices. When loaded with GTP-gamma-S, a
      non-hydrolysable analogue of GTP, vagal neurons generated a persistent inward
      current in the absence of agonist and the oxytocin effect was suppressed,
      suggesting that the peptide-evoked current was mediated by G-protein activation.
      Loading vagal neurons with the calcium chelator 1,2-bis(2-aminophenoxy)ethane
      N,N,N',N',-tetraacetic acid (BAPTA) suppressed a calcium-dependent, slowly
      decaying potassium aftercurrent but did not affect the oxytocin response,
      suggesting that the latter was not mediated by an agonist-induced increase in the
      intracellular calcium concentration. Protein kinase C (PKC) activation was
      probably not involved, since the peptide-evoked current was not modified by
      loading neurons with the PKC inhibitor H7. Thus, the oxytocin-evoked current in
      vagal neurons was probably not mediated by phospholipase C-beta (PLC-beta)
      activation. Loading neurons with 8-Br-cAMP or with an adenylyl cyclase activator
      (forskolin) reduced the oxytocin-evoked current by about half. SQ 22536, an
      adenylyl cyclase inhibitor, reduced this current by a similar amount. However,
      the peptide-evoked current was unaffected by Rp-cAMPS and Sp-cAMPS, an inhibitor
      and an activator, respectively, of cAMP-dependent protein kinase (PKA). We
      suggest that oxytocin activates two distinct signalling pathways in vagal
      neurons: one which is cAMP-dependent, but PKA-independent, and one, unidentified,
      which is PLC-beta-and cAMP-independent. Each pathway accounts for about half of
      the peptide effect and both appear to involve G-protein activation.

PMID- 9517467
TI  - Evidence from confocal fluorescence microscopy for a dense, reciprocal
      innervation between AVP-, somatostatin-, VIP/PHI-, GRP-, and VIP/PHI/GRP
      immunoreactive neurons in the rat suprachiasmatic nucleus.
AB  - The rat suprachiasmatic nucleus (SCN) consists of several classes of neurons
      which can be identified by their transmitter content. Knowledge of putative
      interaction between these different cell types is essential in order to
      understand the possibilities of information processing within the SCN. The aim of
      the present study was therefore to obtain more information about the mutual
      innervation between the main cell classes in the rat SCN, viz. those containing
      the neuropeptides arginine vasopressin (AVP), vasoactive intestinal peptide
      (VIP), peptide histidine isoleucine (PHI), gastrin-releasing peptide (GRP) and
      somatostatin respectively. For this purpose, vibratome sections were double
      immunolabelled for seven different peptide combinations and subsequently analysed
      by high-resolution confocal laser scanning fluorescence microscopy. Attention was
      focused on axosomatic appositions, the occurrence and frequency of which were
      quantitatively estimated. Our analysis of double-immunolabelled sections
      demonstrated that some of the VIP- and some of the GRP-immunoreactive nerve cells
      and endings showed colocalization. Assuming, on the basis of literature data,
      that VIP and PHI are always colocalized at the cellular level, the five main cell
      classes in the SCN appeared to be interconnected, at least axosomatically, in the
      following reciprocal way: AVP <--> VIP/PHI, AVP <--> GRP, AVP <--> somatostatin,
      somatostatin <--> VIP/PHI, somatostatin <--> GRP, VIP/PHI <--> GRP, VIP/PHI/GRP <
      -> GRP, VIP/PHI/GRP <--> VIP/ PHI. In addition to this heterologous axosomatic
      innervation, these cell groups also showed substantial homologous innervation.
      Supported by electron microscope data from the literature showing the existence
      of axodendritic synapses for some of these peptide combinations, our findings
      strongly suggest that the rat SCN comprises a complex synaptic network with
      strong interactive capabilities, which is probably a requisite for its biological
      clock function.

PMID- 9517468
TI  - Pronase acutely modifies high voltage-activated calcium currents and cell
      properties of Lymnaea neurons.
AB  - Pronase E ('pronase') is one of the proteolytic enzymes that are used in
      preparative procedures such as cell isolation and to soften the sheath of
      invertebrate ganglia. Although several effects of proteolytic enzymes on the
      physiology of non-neuronal tissues have been described, the effects of these
      enzymes on central neurons have received little attention. We examined the
      effects of bath-applied pronase on neurons in the Lymnaea central nervous system
      and in vitro. Pronase caused action potential broadening in neurons that exhibit
      a shoulder on the repolarization phase of their action potentials. This effect of
      pronase was accompanied by, although unrelated to, a depolarization and decrease
      in action potential interval. Some, but not all, effects of pronase in the
      central nervous system were reversible. For example, the decreases in membrane
      potential and action potential interval were both reversed after approximately 1
      h of washing with saline. However, the effect of pronase on the action potential
      duration was not reversed after a period of 90 min. The modulation of action
      potential width prompted us to examine Ca2+ currents. Exposure to pronase
      resulted in an increase in both peak and late high voltage-activated Ca2+
      currents in isolated neurons. Pronase neither changed the inactivation rate nor
      caused a shift in the current-voltage relationship of the current. The changes in
      action potential duration could be prevented by application of 0.1 mM Cd2+,
      indicating that the action potential broadening caused by pronase depends on Ca2+
      influx. This is the first systematic study of the acute and direct actions of
      pronase on Ca2+ currents and cell properties both in the CNS and in vitro.

PMID- 9517469
TI  - Olivocerebellar axon regeneration and target reinnervation following dissociated
      Schwann cell grafts in surgically injured cerebella of adult rats.
AB  - The ability of Schwann cells to induce the regeneration of severed
      olivocerebellar and Purkinje cell axons across an injury up to their deafferented
      targets was tested by transplanting freshly dissociated cells from newborn rat
      sciatic nerves into surgically lesioned adult cerebella. The grafted glial cells
      consistently filled the lesion gap and migrated into the host parenchyma.
      Transected olivocerebellar axons vigorously regenerated into the graft, where
      their growth pattern and direction followed the arrangement of Schwann cell
      bundles. Although some of these axons terminated within the transplant, many of
      them rejoined the cerebellar parenchyma beyond the lesion. Here, their fate
      depended on the territory encountered. No growth occurred in the white matter.
      Numerous fibres penetrated into the granular layer and formed terminal branches
      that remained confined within this layer. A few of them, however, regenerated up
      to the molecular layer and formed climbing fibres on Purkinje cell dendrites. By
      contrast, the growth of transected Purkinje cell axons into the grafts was very
      poor. These results underscore the different intrinsic responsiveness of Purkinje
      cell and olivocerebellar axons to the growth-promoting action of Schwann cells,
      and show that the development and outcome of the regenerative phenomena is
      strongly conditioned by the spatial organization and specific features of the
      environmental cues encountered by the outgrowing axons along the course they
      follow. However, Schwann cells effectively bridge the lesion gap, induce the
      regeneration of olivocerebellar axons, and direct their growth up to the
      deafferented host cortex, where some of them succeed in reinnervating their
      natural targets.

PMID- 9517470
TI  - The role of the mouse macrophage scavenger receptor in myelin phagocytosis.
AB  - Myelin phagocytosis during Wallerian degeneration and immune-mediated
      demyelination depends on the action of mononuclear cells of the
      monocyte/macrophage system. The present study investigated the role of the
      macrophage scavenger receptor, a trimeric membrane glycoprotein, in myelin uptake
      by macrophages. Two in vitro models of myelin phagocytosis were used: an organ
      culture model of mouse peripheral nerves exposed to cocultured macrophages and a
      quantitative flow cytometric assay. Different concentrations of the monoclonal
      rat anti-mouse scavenger receptor antibody (2F8) were applied to these systems to
      selectively block the macrophage scavenger receptor. Concentration-dependent
      effects on macrophage migration and myelin uptake were seen when the macrophage
      scavenger receptor was blocked by the antibody 2F8. Low concentrations reduced
      myelin phagocytosis by the invading macrophages; higher concentrations completely
      abolished macrophage invasion of the nerves. Using a quantitative flow cytometric
      assay it was also shown that the 2F8 antibody inhibits phagocytosis of myelin in
      a dose-dependent manner. These data indicate that the macrophage scavenger
      receptor is involved in myelin phagocytosis by macrophages.

PMID- 9517471
TI  - NOS expression in nigral cells after excitotoxic and non-excitotoxic lesion of
      the pedunculopontine tegmental nucleus.
AB  - The substantia nigra (SN) receives afferents from cholinergic neurons of the
      pedunculopontine tegmental nucleus (PPTg), a neuronal population that shows high
      levels of nitric oxide synthase (NOS), the enzyme responsible for the synthesis
      of nitric oxide. We have investigated the effects of the injection in PPTg of two
      neurotoxins, kainic acid (an excitotoxic neurotoxin), and ethylcholine mustard
      azirinium ion (AF64A, a non-excitotoxic neurotoxin), upon the SN cells of the
      rat, by using choline acetyltransferase (ChAT) immunohistochemistry as a marker
      of cholinergic neurons, and nicotinamide adenine dinucleotide phosphate
      diaphorase (NADPHd) histochemistry and NOS immunohistochemistry as markers of
      nitric oxide-producing neurons. Our results show that in normal rats, the SN
      contains two populations of NOS-positive neurons: large cholinergic neurons of
      PPTg that invade the caudal region of the SN, and small elongated neurons lying
      in the SN pars compacta. After ipsilateral PPTg lesion, another population of
      nigral cells, constituted by medium sized neurons, became NADPHd/NOS-positive.
      This was much more evident in AF64A-injected rats, in which many medium sized
      neurons showed enzymatic activity and normal morphological features, at least
      during the 90 days after injection. Kainic acid-injected rats, in contrast,
      showed nigral cell degeneration, an effect not found in AF64A material, and only
      a few NOS-positive neurons. NADPHd/NOS activity was never present in degenerating
      neurons. These findings suggest that induction of NOS activity is not involved in
      nigral cell degeneration, and that nitric oxide could have a protective rather
      than a neurotoxic role. The possible role of nitric oxide in the pathogenesis of
      Parkinson's disease is discussed.

PMID- 9517472
TI  - NMDA receptor modulation by a conditioned medium derived from rat cerebellar
      granule cells.
AB  - Our previous studies have shown that the response to the excitotoxic action of
      glutamate by cultured cerebellar granule cells depends upon the cell density or
      the volume of medium in which they have been grown: the higher the cell density
      or the lower the volume, the higher the response to glutamate. We have
      hypothesized that this variable response is due to the formation in culture of a
      glutamate-sensitizing activity GSA more abundantly in conditioned medium derived
      from high-density or low-volume cultures than that present in low-density or high
      volume cultures and capable of restoring sensitivity in previously resistant
      granule cells. In order to elucidate the mechanism of action of glutamate
      sensitizing activity, we measured the extent and function of NMDA receptors in
      low- and high-volume cultures and assessed the effect of glutamate-sensitizing
      activity on the same receptors. We found that under high-volume conditions the
      extent of MK-801 binding, the amount of NMDA receptor type 1, the currents evoked
      in whole cells after an NMDA pulse and the response of cultured cells to this
      ligand were markedly reduced compared with low-volume cultures. Addition of
      glutamate-sensitizing activity to high-volume cultures increased their glutamate
      sensitivity, the NMDA-evoked currents, the extent of MK-801 binding and the
      amount of NMDA receptor type 1 protein present. The corresponding mRNA
      transcripts, on the contrary, were unchanged in high-volume, low-volume and high
      volume GSA-treated cultures.

PMID- 9517473
TI  - Localization of putative receptors for tetanus toxin and botulinum neurotoxin
      type A in rat central nervous system.
AB  - Clostridial neurotoxins (tetanus and botulinum toxins) are potent blockers of
      neurotransmitter release. These toxins act specifically on the nervous system by
      interacting with still non-identified protein receptors together with
      gangliosides. Whereas many biochemical data are available on their binding
      properties to neuronal membranes in vitro, there is poor morphological evidence
      of their binding to mammalian central nervous system. In the present study, the
      binding of tetanus and botulinum neurotoxin type A to rat brain sections is
      reported. Both toxins bound to nerve terminals with a broad distribution in
      brain. Tetanus toxin additionally bound to nerve fibres. The staining patterns
      were clearly shown to be due to the interaction of the heavy chains, which
      contain the binding moiety, with the tissue. In an attempt to investigate the
      nature of the acceptors present in the tissue, some sections were pre-incubated
      with periodic acid. This treatment resulted in the additional binding of
      botulinum neurotoxin type A to nerve fibres. Since the extended staining of nerve
      terminals was not modified by this pretreatment, it is suggested that protein
      receptors of clostridial neurotoxins are located at the nerve terminals, which
      may be common constituents of the synapses.

PMID- 9517474
TI  - The expression pattern of the orphan nuclear receptor RORbeta in the developing
      and adult rat nervous system suggests a role in the processing of sensory
      information and in circadian rhythm.
AB  - RORbeta is an orphan nuclear receptor related to retinoid and thyroid hormone
      receptors and is exclusively expressed in the central nervous system (CNS). Here
      we present an in situ hybridization analysis of the distribution of RORbeta mRNA
      in the developing and adult rat CNS. The receptor localizes to areas involved in
      the processing of sensory information. In the cerebral cortex, RORbeta mRNA was
      exclusively detected in non-pyramidal neurons of layer IV and, less so, layer V.
      The highest expression was found in primary sensory cortices. In the thalamus
      highest RORbeta expression was found in the sensory relay nuclei projecting to
      the respective cortical areas. In contrast, sensory projection neurons in the
      periphery, for example retinal ganglion cells and neurons of the sensory ganglia
      showed only little RORbeta expression. RORbeta is also expressed in areas
      involved in the generation and maintenance of circadian rhythms - the
      suprachiasmatic nucleus, the pineal gland and the retina. In the latter two
      tissues, RORbeta mRNA abundance oscillates with circadian rhythmicity peaking
      during the hours of darkness. RORbeta mRNA could not be detected in striatum,
      hippocampus, cerebellum, the motor nuclei of the cranial nerves or the ventral
      part of the spinal cord. During development, RORbeta is expressed in many areas
      as early as embryonic day (E) 15, anticipating the distribution pattern in the
      adult. Our data suggest that RORbeta regulates genes whose products play
      essential roles in the context of sensory input integration as well as in the
      context of circadian timing system.

PMID- 9517475
TI  - NMDA receptor activation triggers voltage oscillations, plateau potentials and
      bursting in neonatal rat lumbar motoneurons in vitro.
AB  - Whole-cell recordings of lumbar motoneurons in the intact neonatal rat spinal
      cord in vitro were undertaken to examine the effects of N-methyl-D-aspartate
      (NMDA) receptor activation on membrane behaviour. Bath application of NMDA
      induced rhythmic voltage oscillations of 5.9+/-2.1 mV (SD) at a frequency of
      4.4+/-1.5 Hz. Amplitude, but not frequency, of the voltage oscillations was
      membrane potential-dependent. Voltage oscillations could recruit action
      potentials and/or plateau potentials with or without superimposed bursting.
      Blockade of synaptic transmission with tetrodotoxin (TTX) sometimes resulted in a
      loss of oscillatory activity which could then be restored by increasing the NMDA
      concentration. After application of TTX, the trajectory of NMDA-induced
      oscillations was similar to the trajectory induced in the presence of intact
      synaptic networks, although the mean oscillation duration was longer and the
      oscillation frequency was slower (1.8+/-1.1 Hz). Current ramps delivered after
      bath application of NMDA demonstrated bistable membrane properties which may
      underlie the plateau potentials. Injection of intracellular current pulses could
      initiate, entrain and terminate individual plateau potentials. The results
      suggest that membrane depolarization produced by oscillations may activate other
      intrinsic conductances which generate plateau potentials, thereby providing the
      neuron with enhanced voltage sensitivity, compared to that produced by NMDA
      receptor activation alone. These oscillatory events may have a role in the
      regulation of motor output in a variety of rhythmic behaviours including
      locomotion.

PMID- 9517476
TI  - Phosphorylation-dependent effects of synapsin IIa on actin polymerization and
      network formation.
AB  - The synapsins are a family of synaptic vesicle phosphoproteins which play a key
      role in the regulation of neurotransmitter release and synapse formation. In the
      case of synapsin I, these biological properties have been attributed to its
      ability to interact with both synaptic vesicles and the actin-based cytoskeleton.
      Although synapsin II shares some of the biological properties of synapsin I, much
      less is known of its molecular properties. We have investigated the interactions
      of recombinant rat synapsin Ila with monomeric and filamentous actin and the
      sensitivity of those interactions to phosphorylation, and found that: i)
      dephosphorylated synapsin II stimulates actin polymerization by binding to actin
      monomers and forming actively elongating nuclei and by facilitating the
      spontaneous nucleation/elongation processes; ii) dephosphorylated synapsin II
      induces the formation of thick and ordered bundles of actin filaments with
      greater potency than synapsin I; iii) phosphorylation by protein kinase A
      markedly inhibits the ability of synapsin II to interact with both actin monomers
      and filaments. The results indicate that the interactions of synapsin II with
      actin are similar but not identical to those of synapsin I and suggest that
      synapsin II may play a major structural role in mature and developing nerve
      terminals, which is only partially overlapping with the role played by synapsin
      I.

PMID- 9517477
TI  - Developmentally regulated alternative splicing of mRNAs encoding N-terminal tau
      variants in the rat hippocampus: structural and functional implications.
AB  - Tau protein variants are axonal microtubule-associated phosphoproteins whose
      expression correlates with developmentally regulated neurite outgrowth. A single
      gene encodes multiple tau transcripts via complex alternative splicing. We
      studied the expression of the mRNAs encoding N-terminal variants of tau, and we
      showed distinct alternative splicing of exons 2 and 3 in nervous tissues of the
      adult rat, including the inner ear, hippocampus, cortex, striatum, brainstem,
      cerebellum, olfactory bulb and retina. Using the reverse transcriptase-coupled
      polymerase chain reaction and in situ hybridization, we then focused our
      developmental study on hippocampal neurons, both in vivo and in vitro, to address
      the developmental and spatial expression of the alternatively spliced mRNAs
      encoding N-terminal variants of tau. Tau mRNAs devoid of exons 2 and 3 were
      present throughout development, although their levels decreased in adults. Those
      containing exon 2 but not exon 3 were already present in the hippocampus of
      newborn rats and their levels increased during the first postnatal week, mainly
      in the pyramidal cell layer. Tau RNAs containing exons 2 and 3 appeared at the
      end of this period in the pyramidal cell layer and in the dentate granule cells.
      Exon 2-containing mRNAs seemed to be associated with cells undergoing axonal
      sprouting, while exon 3-containing RNAs were expressed in mature neurons that had
      established their connections. The timing and pattern of tau alternative splicing
      were maintained in cultured hippocampal neurons, suggesting that splicing
      processes are independent of the organized connectivity and of the environmental
      cues provided in vivo. Secondary structure predictions of tau variants revealed
      that the insertion of the exon 3-encoded domain substantially modifies the
      secondary structure of the N-terminal region of tau. This N-terminal
      heterogeneity may confer distinct regulatory roles on the tau variants during
      ontogeny and may contribute to plasticity in the adult rat brain.

PMID- 9517478
TI  - Choline is a selective agonist of alpha7 nicotinic acetylcholine receptors in the
      rat brain neurons.
AB  - In the present study, we demonstrate that choline, a precursor of acetylcholine
      (ACh) and a product of acetylcholine hydrolysis by acetylcholinesterase (AChE),
      acts as an efficient and relatively selective agonist of alpha7-containing
      nicotinic acetylcholine receptors (nAChR) in neurons cultured from the rat
      hippocampus, olfactory bulb and thalamus as well as in PC12 cells. Choline was
      able to activate postsynaptic and presynaptic alpha7 nAChRs, with the latter
      action resulting in the release of other neurotransmitters. Although choline was
      approximately one order of magnitude less potent than ACh (EC50 of 1.6 mM for
      choline and 0.13 mM for ACh), it acted as a full agonist at alpha7 nAChRs. In
      contrast, choline did not activate alpha4beta2 agonist-bearing nAChRs on
      hippocampal neurons, and acted as a partial agonist at alpha3beta4-containing
      nAChRs on PC12 cells. The ethyl alcohol moiety of choline is required for the
      selective action on alpha7 nAChR. Exposure of cultured hippocampal neurons for 10
      min to choline (10-100 microM) resulted in desensitization of the native alpha7
      nAChRs. Moreover, chronic exposure (10 days) of the cultured hippocampal neurons
      to a desensitizing concentration of choline (approximately 30 microM) decreased
      their responsiveness to ACh. The selective action of choline on native alpha7
      nAChRs suggests that this naturally occurring compound may act in vivo as an
      endogenous ligand for these receptors. Putative physiological actions of choline
      include retrograde messenger activity during the development of the mammalian
      central nervous system and during periods of elevated synaptic activity that
      leads to long-term potentiation.

PMID- 9517479
TI  - Developmental changes in neuronal responsiveness to the CNS myelin-associated
      neurite growth inhibitor NI-35/250.
AB  - The extent of fibre regeneration in the adult injured vertebrate nervous system
      appears to be primarily determined by the local environment. Thus, the failure of
      axon regrowth in the central nervous system (CNS) is crucially influenced by the
      presence of the myelin-associated neurite growth inhibitor NI-35/250 and possibly
      also by molecules such as the myelin-associated glycoprotein and the
      proteoglycans. Developmental time course studies have shown that the capacity for
      regeneration declines sharply with the appearance of mature oligodendrocytes and
      myelin, which indicates a role of NI-35/250 in restricting CNS regeneration and
      plasticity. However, recent in vitro and in vivo studies showed that embryonic
      neurons are capable of extending fibres on and in adult CNS tissue apparently
      unaffected by myelinated areas. A possible explanation is that very immature
      neurons have yet to express the appropriate receptors and response mechanisms for
      factors that normally induce growth inhibition at a later stage of development.
      Here we report that embryonic rat dorsal root ganglion and chick retinal ganglion
      cells display different sensitivity to bovine NI-35/250 compared with mature
      neurons. In older neurons NI-35/250 could evoke long-lasting collapse responses
      accompanied by a large increase in the intracellular calcium level, persisting
      for several minutes. In contrast, their embryonic counterparts collapsed only
      transiently when exposed to NI-35/250, and increases in intracellular calcium
      concentration were small and transient. Calcium influx induced experimentally by
      the calcium ionophore A23187 revealed that it was not the maximal size of the
      calcium increase but rather the duration of elevated calcium concentration that
      was the most important determinant for subsequent morphological alterations of
      the growth cone. Our data further suggest that developing neurons acquire their
      complete sensitivity for NI-35/250 around the time of myelination.

PMID- 9517480
TI  - Rat mature sympathetic neurones derive neurotrophin 3 from peripheral effector
      tissues.
AB  - In a previous study we have demonstrated that endogenous neurotrophin 3 (NT3) is
      required for the survival of most sympathetic neurones in postnatal rats.
      However, the mechanisms underlying the action of NT3 on sympathetic neurones is
      not known. Neither is it understood whether NT3 is retrogradely transported from
      peripheral tissues or acts locally in an autocrine fashion. In the present study,
      NT3-mRNA was quantified in sympathetic effector tissues and NT3 protein was
      localized in intact and lesioned sympathetic nerves in rats. NT3-mRNA is
      expressed and developmentally regulated in many effector tissues including
      mesenteric arteries, salivary gland, heart and kidney but hardly detectable in
      the superior cervical ganglia of adult animals. The majority of sympathetic
      neurones express immunoreactivity for TrkA and TrkC in both neonatal and adult
      rats. Sympathetic somata are normally immunoreactive for NT3, but the
      immunoreactivity is abolished by systemic administration of NT3 antibodies or
      axotomy of postganglionic neurones, suggesting an accumulation of NT3 from
      extraneuronal sources. Furthermore, the detection of NT3-immunoreactivity in the
      internal carotid nerve as early as 3 h following a compression and only on the
      distal side indicates endogenous NT3 is retrogradely transported by sympathetic
      neurones. These studies provide evidence indicating that NT3, like nerve growth
      factor, is an effector tissue-derived neurotrophic factor for sympathetic
      neurones both during development and in the adult animal. Thus, we have provided
      a clear example that one type of neurone derives, through a retrograde transport
      mechanism, two neurotrophic factors simultaneously from its peripheral effector
      tissues.

PMID- 9517481
TI  - Activation of gp130 by IL-6/soluble IL-6 receptor induces neuronal
      differentiation.
AB  - Interleukin-6 (IL-6) on target cells binds to the specific IL-6 receptor (IL-6R)
      and subsequently induces homodimerization of the signal-transducing protein
      gp130. Cells which express gp130 but no IL-6R and which therefore do not respond
      to IL-6 can be stimulated by the complex of IL-6 and soluble IL-6R (slL-6R). Here
      we show that on rat pheochromocytoma cells (PC12), the combination of IL-6 and
      slL-6R but not IL-6 alone induces expression of c-fos, GAP-43 and neuron-specific
      enolase followed by neuron-specific differentiation and formation of a neuronal
      network. The differentiation was dose-and time-dependent and followed the same
      kinetics as nerve-growth factor (NGF)-induced differentiation. The responses of
      PC12 cells to IL-6/sIL-6R and NGF were additive, suggesting independent signaling
      pathways. We demonstrate that activation of gp130 generates a neuronal
      differentiation signal that is equivalent to and independent of trk/NGF receptor
      tyrosine kinase. Interestingly, the failure of IL-6 to induce differentiation of
      PC12 cells is not due to lack of surface expression of IL-6R as IL-6 alone
      triggered expression of GAP-43 mRNA and protein. We hypothesize that PC12 cells
      express more gp130 than IL-6R and that the extent of activated gp130 molecules
      determines the quality of the response.

PMID- 9517482
TI  - Effects of neurotransplants and BDNF on the survival and regeneration of injured
      adult spinal motoneurons.
AB  - We compared the effects of peripheral nerve grafts, embryonic spinal cord
      transplants and brain-derived neurotrophic factor (BDNF) on the survival and axon
      regeneration of adult rat spinal motor neurons undergoing retrograde degeneration
      after ventral root avulsion. Following implantation into the dorsolateral
      funiculus of the injured spinal cord segment, neither a peripheral nerve graft
      nor a combination of peripheral nerve graft with embryonic spinal cord transplant
      could prevent the retrograde motor neuron degeneration induced by ventral root
      avulsion. However, intrathecal infusion of BDNF promoted long-term survival of
      the lesioned motor neurons and induced abundant motor axon regeneration from the
      avulsion zone along the spinal cord surface towards the BDNF source. A
      combination of ventral root reconstitution and BDNF treatment might therefore be
      a promising means for the support of both motor neuron survival and guided motor
      axon regeneration after ventral root lesions.

PMID- 9517483
TI  - Peripheral noxious stimulation induces CREM expression in dorsal horn:
      involvement of glutamate.
AB  - Peripheral noxious stimulation is known to trigger signalling cascades in neurons
      of the spinal cord. The response to pain and stress at the level of gene
      expression involves transcriptional activation of several cyclic AMP responsive
      genes. Here, we show induction of the CREM (cyclic-AMP responsive element
      modulator) gene in distinct subpopulations of spinal cord neurons upon thermal
      noxious stimulation. The addition of forskolin or glutamate to cultured spinal
      cord neurons results in the induction of the CREM isoform, ICER (Inducible cyclic
      AMP Early Repressor), a powerful repressor of cAMP-induced transcription.
      Overexpression of ICER in cultured spinal cord neurons results in the repression
      of the c-fos and c-jun promoters induced by forskolin and glutamate. On this
      basis, we postulate that early activation of ICER in spinal cord participates in
      the attenuation of early gene induction following noxious stimulation.

PMID- 9517484
TI  - Changes in fatty acid composition of lipids from birds, rodents, and preschool
      children exposed to lead.
AB  - Chronic treatment with inorganic lead (Pb) has been shown to increase the
      proportion of arachidonic acid (ArA), as well as the arachidonate/linoleate
      (ArA/LA) ratio, in the fatty acids of lipids from a variety of avian tissues.
      Changes in two fatty acid-mediated phenomena, peroxidation of membrane lipids and
      synthesis of eicosanoid cytokines, are associated with this enhanced ArA content.
      The authors are not aware of any reports in the literature in which these effects
      of Pb have been described for any animals other than birds. In the current study,
      the authors investigated the effect of Pb on lipid metabolism in three species:
      avian, rodent, and human. The group of children identified as suffering
      environmental Pb exposure were from a Pb-surveillance program and had blood Pb
      concentrations (PbB) averaging 23 microg/dL. Turkey poults fed 100 ppm dietary Pb
      as Pb acetate-trihydrate for 19 d had a PbB of 46 microg/dL. Gastric intubation
      of rats with 80 mg Pb/kg/d for 10 d resulted in a PbB of 74 microg/dL. We
      analyzed fatty acid composition of whole blood from children, poults, and virgin
      rats. Low-dose (nongrowth inhibitory) Pb exposure resulted in significantly
      increased ArA concentration and ArA/LA ratio in blood from all species. Also
      analyzed were plasma and liver of poults, virgin rats, and pregnant rats and
      their fetuses. In plasma and liver from Pb-treated poults and virgin rats, ArA
      and the ArA/LA ratio were again enhanced. Pb intoxication also affected omega3
      composition, increasing the concentrations of all long-chain omega3 fatty acids
      of fetuses from Pb-treated pregnant dams. The authors propose that altered fatty
      acid metabolism may be responsible for some indications of Pb poisoning. Possible
      consequences mediated through lipid peroxidation and production of ArA-derivative
      eicosanoids are considered.

PMID- 9517485
TI  - The relative effectiveness of human plasma glutathione peroxidase as a catalyst
      for the reduction of hydroperoxides by glutathione.
AB  - To reveal clues to the function of human plasma glutathione peroxidase (GPx), we
      investigated its catalytic effectiveness with a variety of hydroperoxides.
      Comparisons of hydroperoxides as substrates for plasma GPx based on the ratio of
      Vmax/Km were blocked by the limited solubility of the organic hydroperoxides,
      which prevented kinetic saturation of the enzyme at the chosen glutathione
      concentration. Therefore, we compared the hydroperoxides by the fold increase in
      the apparent first-order rate constants of their reactions with glutathione owing
      to catalysis by plasma GPx. The reductions of aromatic and small hydrophobic
      hydroperoxides (cumene hydroperoxide, t-amyl hydroperoxide, t-butyl
      hydroperoxide, paramenthane hydroperoxide) were better catalyzed by plasma GPx
      than were reductions of the more "physiological" substrates (linoleic acid
      hydroperoxide, hydrogen peroxide, peroxidized plasma lipids, and oxidized
      cholesterol).

PMID- 9517486
TI  - High fructose intake significantly reduces kidney copper concentrations in
      diabetic, islet transplanted rats.
AB  - Trace element status is known to be altered in the diabetic state, although the
      factors affecting trace element homeostasis in this condition are not well
      understood. The authors examined the effects of a high fructose diet (40% wt:wt)
      vs a control diet on the copper (Cu), zinc (Zn), and iron (Fe) concentrations in
      the kidney, plasma, and red blood cells of islet transplanted (TX) and sham
      operated (SHAM) rats. Male, Wistar Furth rats made diabetic by streptozotocin
      injection (55 mg/kg, iv) were given an intraportal islet transplant (1000
      islets); control animals were sham-injected, sham-operated (SHAM). Rats within TX
      and SHAM groups were assigned to either a high fructose diet (40% fructose, 25%
      cornstarch, FR) or a purified control diet (33% cornstarch, 33% dextrose, CNTL)
      containing identical amounts of mineral mixture for a period of 6 wk. Kidney Cu
      concentration was significantly elevated among hyperglycemic TX-CNTL rats (224+/
      25 nmol/g wet wt), but was markedly reduced in hyperglycemic TX-FR rats (109+/-14
      nmol/g) relative to normoglycemic controls. This occurred in spite of similar
      levels of glucose, insulin (fed and fasted), insulin secretory capacity, body
      weight, and food intake in the TX-CNTL and TX-FR groups. Among the subgroup of
      rats with normal glucose levels post-TX, kidney Cu levels normalized and were
      unaffected by dietary treatment (normoglycemic TX-CNTL = 60+/-5 nmol/g;
      normoglycemic TX-FR = 40+/-2 nmol/g). Kidney Cu concentrations also were
      unaffected by fructose feeding in SHAM animals (CNTL, 60+/-4 nmol/g and FR, 51+/
      5 nmol/g). Kidney Zn and Fe concentrations were similar among the treatment
      groups. Plasma and red blood cell (RBC) Cu, Zn, and Fe concentrations were also
      similar among the groups. Since fructose feeding led to a substantial reduction
      of kidney Cu concentrations in the presence of hyperglycemia, the authors suggest
      that this model can be useful in examining effects of altered kidney Cu
      accumulation in the diabetic animal.

PMID- 9517487
TI  - Study of the age and sex dependence of trace elements in hair by correspondence
      analysis.
AB  - The aim of the study was to examine the potential of multidimensional analysis,
      and in particular of correspondence analysis (CA), in bringing to light the
      influence of sex and age on trace element (TE) concentrations in hair from an
      unselected French population. Sixteen elements (S, Hg, Se, Zn, Pb, Cd, Ni, Co,
      Mn, Fe, Cr, Mg, Al, Ca, Cu, Ag) were assayed by inductively coupled argon plasma
      (ICAP) emission spectroscopy in the scalp hair of 135 men and 346 women. In spite
      of the high background noise, CA was able to reveal the differing patterns in
      males and females. For instance, in this population, higher relative levels of
      the essential elements, Ca, Mg, Zn, and Cu, but also of Ag, characterized women's
      hair, whereas higher relative levels of the heavy metals, Fe and Pb, were
      associated with men's hair. Al and Ag were unexplainedly high in the hair of the
      youngest members of the population. The Cu and Co of youth seemed to give way to
      a predominance of Zn in maturity. The hair of individuals in their forties tended
      to be richest in Ca and Mg, but these elements decreased with advancing age.
      Heavy metals (Hg, Pb, Fe) accumulated with age, whereas Se, Mn, and Cr seemed
      independent of age. CA is manifestly a very useful tool for revealing underlying
      dimensions in complex dynamic systems and unsuspected relationships among
      variables. Clearly, the significance of the high Al and Ag contents in the hair
      of certain members of the population, especially of the very young, needs to be
      investigated from both physiological and toxicological aspects.

PMID- 9517488
TI  - Comparison between levels of trace elements in normal and cancer inoculated mice
      by XRF and PIXE.
AB  - Determination of Rb, Br, Se, Zn, Cu, Fe, and Br/Rb ratio in tissues of mice
      inoculated with colon and melanoma cancer cells is described. A group of 19
      Balb/c mice inoculated with C26 colon carcinoma, 4 C57B1/6 mice inoculated with
      B16 melanoma, and 13 control mice of both kinds were under investigation. The
      study was conducted on samples of blood, liver, kidneys, colon, and skin, and the
      trace element levels in normal and inoculated mice were compared. The inoculation
      was by subcutaneous injection either at the back or intrafootpad. The blood
      samples were taken 1, 2, and 3 wk after inoculation, and after 4 wk all the
      animals were sacrificed. Two nondestructive, complementary analytical methods
      were used: a modified X-ray fluorescence (XRF) for solid tissue and particle
      induced X-ray emission (PIXE) for blood samples. The detection limit (DL) in the
      PIXE method was 0.35 microg/g dry wt in 600 s counting time and in XRF, 1
      microg/g dry sample for Rb, Br, Se and Zn and 2 microg/g for Cu and Fe in 200 s
      counting time. In all the cases studied, cancerous tissue developed at the site
      of the injection, and a significant difference in the trace element levels was
      observed between tissue samples obtained from normal and inoculated mice. The
      most pronounced effect was an increase in Rb level in the tumor by a factor
      ranging between 4 and 10 relative to normal tissue, with a corresponding decrease
      in the Br/Rb ratio (p < 0.05). Smaller changes were found in the Br, Se, Zn, and
      K levels. The changes in trace element levels in the inner organs were much
      smaller and seem to be influenced by the site of injection.

PMID- 9517489
TI  - The competition between transferrins labeled with 59Fe, 65Zn, and 54Mn for the
      binding sites on lactating mouse mammary gland cells.
AB  - Using a homologous competition of 54Mn-transferrin with Mn-transferrin and 65Zn
      transferrin with Zn-transferrin, it was found that on the plasma membrane of
      lactating mouse mammary gland cells there are receptor binding Mn-transferrin and
      Zn-transferrin. The heterologous competition between labeled and nonlabeled Fe
      transferrin, Mn-transferrin and Zn-transferrin, as well as almost equal affinity
      constants of cellular receptors toward the three metals by competition of Fe
      transferrin suggests that one and the same receptor accepts all three metals from
      the transferrin molecule. The cell receptors therefore possess a polymetal
      binding function. A model and a mechanism for regulation of the transport metal
      flow toward the mammary gland cell acting like "automated switching over" are
      proposed.

PMID- 9517490
TI  - Lipid peroxidation in liver of mice administrated with nickel chloride: with
      special reference to trace elements and antioxidants.
AB  - The relationship between Ni-induced hepatic lipid peroxidation (LPO) and the
      concentrations of Ni and trace elements was investigated in male ICR mice. The
      protective effects of antioxidants were also examined. Hepatic LPO and the
      concentrations of Ni, Fe, Cu, and Zn in the liver were enhanced after an ip
      injection of nickel chloride (NiCl2). Dose-response studies were conducted on
      male mice with different groups being injected with 50, 85, and 170 micromol
      Ni/kg. LPO increased significantly in a dose-dependent manner. In time-course
      studies, mice were administrated NiCl2 (170 micromol Ni/kg) and killed at
      intervals of 6, 12, 24, and 48 h after injection. Both LPO and the accumulation
      of Ni, Fe, Cu, and Zn in the liver showed a significantly positive time-course
      relationship after NiCl2 injection. At 1 h and 24 h after a single ip injection
      of 170 micromol Ni/kg, the mice were given an ip injection of ascorbic acid (vit
      C), glutathione (GSH), and selenium (Se). Vit C and GSH significantly decreased
      both the level of hepatic LPO and the concentration of Ni in the liver, but did
      not decrease the accumulation of Fe, Cu, and Zn. However, LPO in the experimental
      group of mice was different significantly from that in the control group. In
      conclusion, the results suggest that Ni-induced hepatic LPO may result from
      increasing the amounts of Ni, Fe, and Cu, since these elements are involved in
      the generation of hydroxyl radical by inducing the Fenton reaction, thus
      instigating the Ni-mediated hepatic LPO. The protective effects of vit C and GSH
      in hepatic LPO result not only from removing the oxygen reactive species, but
      also from decreasing the Ni concentration.

PMID- 9517491
TI  - Effect of aluminum on iron-induced lipid peroxidation and protein oxidative
      modification of mouse brain homogenate.
AB  - In the present study the authors report on the enhancing effect of aluminum(III)
      (Al[III]) on iron(II)(Fe[II])-induced lipid peroxidation (LPO) of mice brain
      homogenate, which occurs in a concentration- and time-dependent manner. No
      evidence of LPO caused by Al alone was found. Both Al(III) and Fe(II) ions
      induced protein oxidative modifications in mice brain homogenate, in a time- and
      concentration-dependent manner. Aluminum enhances Fe(II)-induced protein
      oxidative modification at a concentration of 2:1 and 1:1 Al:Fe molar ratios.
      However, Al suppress Fe(II)-induced protein oxidative modification at a
      concentration of 0.5:1 Al:Fe molar ratio. Addition of ethylenediaminetetraacetic
      acid (EDTA) inhibits both LPO and protein oxidative modifications induced by
      Al(III) and Fe(II) ions. Addition of mannitol and of superoxide dismutase (SOD)
      did not show such effects. It is concluded that in mice brain homogenate, Al
      accelerates Fe(II)-induced LPO. Protein oxidative modifications caused by Fe(II)
      and/or Al ions are enhanced at high, but suppressed at low concentrations of Al
      ions. The latter observation suggests a possible biological role of Al as an
      antioxidant.

PMID- 9517492
TI  - Age-related changes of mineral contents in the human aorta and internal thoracic
      artery.
AB  - To elucidate accumulations of minerals in the human aorta and internal thoracic
      artery, their relative contents (RCs) of minerals were analyzed by inductively
      coupled plasma atomic emission spectrometry. Aortas from 47 men and 24 women
      subjects were examined. The ages of these subjects ranged from newborn to 99 yr.
      After the age of 40 yr, RCs of calcium and phosphorus began to increase, and
      thereafter increased stepwise in the 50s and 70s. In the 70s, their accumulations
      were markedly increased. Internal thoracic arteries from 16 men and 7 women
      subjects were examined. These subjects ranged in age from 65-93 yr. It was found
      that all the RCs of calcium were low, <5.0 mg/g dry wt, and there was no age
      dependent increase of calcium contents in internal thoracic arteries.

PMID- 9517493
TI  - Fermentation of soybean meal with Aspergillus usamii improves zinc availability
      in rats.
AB  - Soybean meal was fermented with Aspergillus usamii to improve zinc availability
      through the degradation of phytic acid. Rats fed a diet containing fermented
      soybean meal showed greater femoral zinc than did animals fed a diet containing
      regular soybean meal. Zinc solubility in the small intestine was higher in the
      rats fed fermented soybean meal than in the rats fed regular soybean meal. These
      results suggested that fermentation with Aspergillus usamii improved zinc
      availability in dietary soybean meal, which was induced by the increase of zinc
      solubility in the small intestine. Adding the same amount of phytate that was
      contained in the regular soybean meal-based diet did not affect the amount of
      zinc present in rats fed a fermented soybean meal-based diet with sodium phytate.
      Phytase activity was found in fermented soybean meal, and this activity may
      degrade added phytate in fermented soybean meal-based diet.

PMID- 9517494
TI  - High dose therapy and autologous stem cell transplantation in follicular non
      Hodgkin's lymphoma.
AB  - Indolent follicular lymphomas are diseases which are generally incurable with
      conventional therapy. Although patients can survive for prolonged periods, the
      median duration of first remissions is about 2.5 years, and subsequent remissions
      progressively shorten with time. High dose therapy with hematopoietic stem cell
      support leads to prolonged disease-free and overall survival in a subset of
      patients with aggressive non-Hodgkin's lymphoma. Mounting evidence suggests
      similar findings for selected patients with indolent follicular non-Hodgkin's
      lymphoma. Presently it remains unclear as to when this approach should be used,
      however inferior results have been seen in heavily pretreated patients. In
      contrast, encouraging results are being reported in patients undergoing such
      treatment early in the course of their disease. Despite these data, many patients
      continue to relapse and future investigations now focus on eradication of minimal
      residual disease.

PMID- 9517495
TI  - The diagnostic and prognostic value of bone marrow immunostaining in
      myelodysplastic syndromes.
AB  - Immunohistochemistry has been introduced as a means of increasing the diagnostic
      accuracy of bone marrow biopsy (BMB) in myelodysplastic syndromes (MDS); more
      recently the possibility of coupling immunostaining with other investigational
      techniques has broadened the spectrum of applications to the biology and
      physiopathology of MDS. Using panels of monoclonal antibodies (MoAbs), various
      histological classifications of MDS have been proposed as an alternative to the
      FAB criteria. The use of lineage-specific MoAbs has allowed a deeper insight into
      the dysplastic features of early hematopoietic precursors. The study of various
      gene products involved in the regulation of cell growth, proliferation and
      sensitivity to antineoplastic drugs, has revealed significant differences between
      MDS and morphologically-related disorders, particularly acute myelogenous
      leukemias (AML); these can be considered markers of a biological difference
      between the two groups of disorders and deserve consideration when designing
      therapeutic strategies for MDS. Both an increase in the percentage of cell
      positivity for the CD34 glycoprotein and a tendency of positive cells towards
      forming aggregates have been shown to be reliable predictors of leukemic
      transformation and survival, irrespective of the FAB subtype; furthermore, CD34
      positivity has also proved to be a better prognostic factor than the presence of
      the abnormal localization of immature precursors (ALIP) on BMB. Finally, the
      simultaneous occurrence of "large" and CD34 positive aggregates can be proposed
      as a means of recognizing MDS patients with an exceedingly unfavourable
      prognosis, and who are therefore suitable for early aggressive therapy.

PMID- 9517496
TI  - The effect of interferon-alpha on beta-1 integrin mediated adhesion and growth
      regulation in chronic myelogenous leukemia.
AB  - There is considerable interest in understanding the mechanisms by which
      interferon-alpha can induce hematological and cytogenetic remissions and prolong
      survival in patients with chronic myelogenous leukemia (CML). There is evidence
      that the selective expansion and growth advantage of malignant hematopoietic
      progenitors in CML may be related, at least in part, to their deficient
      responsiveness to normal negative regulation by the marrow stromal
      microenvironment and that interferon-alpha may restore normal hematopoiesis in
      CML by restoring normal microenvironmental regulation of malignant CML progenitor
      proliferation. In normal hematopoiesis, beta1 integrin receptors mediate
      progenitor adhesion to stroma. Stimulation of beta1 integrin receptors on normal
      progenitors results in transmission of proliferation inhibitory signals. CML
      progenitors demonstrate defective beta1 integrin receptor-mediated adhesion and
      regulation of proliferation. We have shown that interferon-alpha can restore both
      beta1 integrin mediated adhesion as well as integrin-mediated proliferation
      inhibition of CML progenitors. Interferon-alpha enhances CML integrin function
      through direct effects on CML progenitors as well as indirect effects on stroma.
      Restored beta1 integrin-mediated regulation of malignant CML progenitor
      proliferation may result in restoration of normal hematopoiesis in CML patients
      treated with interferon-alpha. There is evidence that abnormal integrin mediated
      signaling in CML progenitors may result from abnormalities in integrin
      cytoskeletal interactions induced by the p210BCR/ABL tyrosine kinase. Although
      the exact mechanisms by which interferon-alpha restores normal integrin signaling
      in CML are not known, preliminary studies indicate that this may at least partly
      be related to the restoration of normal integrin-cytoskeletal interactions. The
      above studies offer some insights into the mechanisms of abnormal hematopoietic
      regulation in CML and the mechanisms by which interferon-alpha may restore normal
      hematopoiesis, in this disease.

PMID- 9517497
TI  - Human herpesvirus 8 (HHV-8) in the pathogenesis of Kaposi's sarcoma and other
      diseases.
AB  - The discovery of Kaposi's Sarcoma-associated herpesvirus/human herpesvirus-8
      (KSHV/ HHV-8) and subsequent studies of this virus have provided a body of
      evidence that support the concept that this is an etiologic agent for Kaposi's
      sarcoma (KS). Several studies have indicated that this virus may also be a causal
      agent for primary effusion lymphoma (PEL) and Castleman's disease as well. First
      generation serologic assays for HHV-8 have now been developed. The preponderance
      of data suggest that the incidence of HHV-8 infection is highest in populations
      at risk for KS: male homosexuals, immunosuppressed patients, and those who live
      in endemic regions. HHV-8 encodes for functional homologs of human proteins that
      may play a role in the development of disease. As we learn more about the steps
      by which this virus can lead to KS and/or other diseases, rational therapies and
      preventative strategies may be possible.

PMID- 9517498
TI  - The granulocyte colony-stimulating factor receptor and its role in disorders of
      granulopoiesis.
AB  - The granulocyte colony-stimulating factor receptor (G-CSFR) critically regulates
      granulopoiesis. Defects in G-CSFR expression due to targeted disruption of the G
      CSFR gene or the genes for the transcription factors C/EBPalpha and PU.1 result
      in decreases in hematopoietic progenitor cell numbers and neutropenia. Mutations
      in the G-CSFR gene disrupt its normal signaling functions and appear to
      contribute to leukemogenesis. Acquired mutations in the G-CSFR resulting in
      truncation of the distal cytoplasmic region that mediates maturation and growth
      arrest signaling have been reported in patients with severe congenital
      neutropenia (SCN) and acute myelogenous leukemia (AML). A role for G-CSFR
      mutations in the pathogenesis of other disorders is speculated. This review will
      summarize the current state of knowledge of the G-CSFR and its role in disorders
      of granulopoiesis.

PMID- 9517499
TI  - Expression of the retinoblastoma tumor suppressor gene (RB-1) in acute leukemia.
AB  - In this report we review current studies concerning the RB-1 gene expression in
      acute leukemias. The RB-1 gene was analyzed in several studies by protein-, RNA
      and DNA-techniques in acute lymphoblastic leukemia (ALL) as well as in acute
      myelogenous leukemia (AML). The frequency of RB-1 inactivation in ALL-patients
      ranged between 30% and 64% in several studies. Structural abnormalities of the RB
      1 gene were reported in 18% of ALL-patients and in 27% of Philadelphia chromosome
      positive ALL, respectively. The proportion of AML-patients with absent RB-1
      protein expression ranged between 19% and 55%. Structural RB-1-abnormalities in
      AML were predominantly reported in leukemias with monocytic differentiation.
      Furthermore, the prognostic value of an abnormal RB-1 gene expression was also
      estimated in some studies. In childhood ALL RB-1 inactivation was reported to
      have prognostic significance while in contrast, in another study on adults no
      prognostic value of RB-1 was found. In 4 out of 5 documented studies AML-patients
      with RB-1 inactivation generally had a poorer prognosis. In conclusion, RB-1
      inactivation is frequently observed in acute leukemia. The prognostic value of
      low RB-1 expression is controversial but the majority of published studies found
      low RB-1 expression to be a negative prognostic predictor, in acute leukemia.

PMID- 9517500
TI  - The pathologic significance of the immunoglobulins expressed by chronic
      lymphocytic leukemia B-cells in the development of autoimmune hemolytic anemia.
AB  - The increased number of CD5+ B-cells in some human autoimmune diseases, the
      frequent commitment of CD5+ B-cells to the production of natural autoantibodies,
      and the apparent involvement of these cells in the pathogenesis of the autoimmune
      hemolytic anemia (AIHA) in certain mouse models suggests a causal relationship
      between the CD5+ chronic lymphocytic leukemia (CLL) B-cell and the AIHA which
      frequently develops in this malignant disorder. In support of this conclusion is
      our recent finding that the VH region gene repertoire of the leukemic B-cells
      from CLL patients with AIHA is rather biased and characterised by the over
      representation of the 51p1 VH gene. On the other hand, it appears relatively
      certain that the pathogenic anti-erythrocyte antibodies in CLL patients with AIHA
      are produced by remnant normal B-cells, and that the antibodies expressed by the
      leukemic CD5+ B-cells do not directly bind red blood cells (RBC). Of interest,
      the antibodies produced by the leukemic B-cells from CLL patients with AIHA might
      have in common rheumatoid factor (RF) activity. These data indicate that the
      antibodies produced by the leukemic B-cells from CLL patients with AIHA are not
      directly involved in red blood cell destruction, but may be involved in the
      induction or amplification of a polyclonal anti-RBC response. Finally, we discuss
      the possible clinical implications of our finding that CLL patients with leukemic
      cells expressing the 51p1 VH gene may be at a higher risk to develop autoimmune
      hemolytic anemia.

PMID- 9517501
TI  - Use of the international prognostic index and the tumor score to detect poor-risk
      patients with primary mediastinal large B-cell lymphoma: a study of 37 previously
      untreated patients.
AB  - We tested two prognostic models devised for intermediate-grade lymphomas, the age
      adjusted international prognostic index and the tumor score, in 37 consecutive
      untreated patients treated for a diagnosis of primary mediastinal large B-cell
      lymphoma (PMLCL). Neither model selected for a group of patients with
      statistically significant differences in rates of complete response, failure-free
      survival (FFS) and overall survival (OS). Because the level of beta microglobulin
      (beta2m) is consistently low in the serum of patients with PMLCL despite bulky
      disease, we tested the median value of this continuous variable in the 37
      patients and found it to be statistically significant for predicting FFS. A
      hypothetical tumor score model using the adjusted value for beta2m improved the
      prognostic accuracy for achievement of complete response (93% vs. 60%; P = 0.02),
      FFS (73% vs. 35%; P = 0.02), and OS (80% vs. 55%; P = 0.05). This hypothetical
      model merits further testing in a larger population of patients with PMLCL.

PMID- 9517503
TI  - Intensified induction chemotherapy with high dose cytarabine and etoposide for
      acute myeloid leukemia: a review and updated results of the Australian Leukemia
      Study Group.
AB  - Induction therapy of acute myeloid leukemia (AML) with standard dose chemotherapy
      will result in approximately 55-75% of patients achieving a complete remission
      (CR). Intensification of induction treatment with etoposide and high dose
      cytarabine does not alter the CR rate but appears to significantly improve the
      subsequent outcome. Updated results of the comparison of high dose cytarabine
      with daunorubicin and etoposide in induction (HIDAC-3-7) versus a standard dose
      combination (7-3-7) demonstrated a highly significant increase in relapse free
      survival, (RFS) on the high dose arm (p = 0.007) with RFS of 48% at 5 years with
      HIDAC-3-7 and 25% on 7-3-7. The high dose arm had a more modest survival
      advantage at 5 years of 33% compared with 25% on standard treatment, possibly
      because of a higher initial death rate with HIDAC-3-7. The improvement seen in
      patients with CR after high dose induction appear to parallel results obtained
      with post-remission therapies intensified with high dose cytarabine. These
      studies provide clinical evidence that a dose-response effect is present for
      cytarabine in AML. Intensified treatment is more toxic, gives more profound
      myelosuppression post-remission and has been shown to benefit younger patients
      only. Issues of patient selection and the optimal placement of intensification in
      the treatment sequence require further study. In the future, it is likely that
      remission duration may be a useful clinical tool to study the influence of new
      induction therapies on residual resistant leukemia.

PMID- 9517502
TI  - A phase I trial of high dose ProMACE-CytaBOM with granulocyte colony stimulating
      factor for patients with non-Hodgkin's lymphoma.
AB  - We hypothesized that the conventional ProMACE-CytaBOM regimen could be improved
      by administering all drugs on d1 with the S-phase agents first in the sequence,
      prednisone d2-6 only, increasing doxorubicin to 50 mg/m2, and adding G-CSF d2-13
      to ameliorate neutropenia. This regimen was tested in a Phase I study of 20
      patients (pt) with non-Hodgkin's lymphoma (NHL). The median age was 61 yrs
      (range, 29-79). Four pt had low grade and 16 intermediate/high NHL. The
      International Prognostic Index was low in 6 cases, low-intermediate in 12, and
      high-intermediate in 2. Twelve pt received > or =6 cycles; 4 had 5 cycles, 3 had
      4 cycles, and 1 received only 1 cycle. Sixteen pt received subsequent cycles
      without delay. The response rate was 95% (19/20) with 12 CR and 7 PR; one pt
      progressed during treatment. After a median follow-up of 30 months, 85% (17/20)
      remain alive. This higher dose ProMACECytaBOM regimen can be given to older adult
      patients in an outpatient setting. Phase III studies would be required to
      determine if it produces a superior overall survival compared to other regimens.

PMID- 9517504
TI  - PreB1 (CD10-) acute lymphoblastic leukemia: immunophenotypic and genomic
      characteristics, clinical features and outcome in 38 adults and 26 children. The
      Groupe dEtude Immunologique des Leucemies.
AB  - The less differentiated stage (CD10-) of B-lineage acute lymphoblastic leukaemia
      (ALL) described as preB1-ALL in the GEIL nomenclature, accounts for less than 10%
      of ALL. It is classically considered to be associated with translocation
      (4;11)(q21;q23), and to have a poor prognosis. We report an extensive
      immunophenotypic, genomic and clinical study of a series of 64 preB-1 ALL
      patients, representing 6.3% of a cohort of consecutive ALLs. The engagement of
      preB1-ALL cells in the B-lineage was confirmed by their B-lineage score, equal to
      or higher than 2. In addition, more than 90% of the cases tested showed
      rearranged IGH genes. Translocation (4;11) was the most frequent karyotypic
      anomaly seen, but only accounted for 24% of the preB1-ALL cases tested.
      Expression of the myeloid associated antigen CD15 was also found with high
      incidence in this subset. Clinical and biological features at presentation showed
      more significant differences between preB1- and T-ALL than between preB1- and
      preB2-ALL (CD10+). However, outcome characteristics of the 22 children with preB1
      ALL confirmed the worse prognosis of this entity.

PMID- 9517505
TI  - Influence of malignant cell clonogenic capacities and position along the
      maturation pathway on their susceptibility to lymphokine-activated killer cell
      cytotoxicity.
AB  - In order to investigate the sensitivity of malignant target cells to lysis by LAK
      cells according to their clonogenic capacities and their position along the
      maturation pathway, we compared clonogenic and chromium release cytotoxicity
      assays performed on human hematopoietic cell lines using Effector: Target ratios
      of 1:1, 3:1, 6:1, 12:1, 24:1, 48:1 and 96:1, and studied the sensitivity of HL-60
      and U937 human cell lines after exposure to different factors including GM-CSF,
      SCF, IFN, Retinoic acid (RA), DMSO, and TPA which are able to recruit cells into
      the cell cycle or to induce cell differentiation. There was a good correlation
      between the lysis of the target cells using 51Cr release and the growth
      inhibition in semisolid medium. The degree of inhibition was significantly higher
      using the colony growth assay (p = 0.006). Regarding the effects of culturing
      cell lines with proliferating and differentiating agents on the sensitivity of
      these cell lines to LAK cytolysis, a correlation was noted between the
      proliferative response of the U937 cell line and susceptibility to LAK cell lysis
      (p = 0.01), while results appeared close to significance with HL-60. The most
      significant effects were a decreased sensitivity of HL-60 to LAK lysis with RA (p
      < 0.001) and TPA (p < 0.001), and an increased susceptibility of U937 to LAK
      lysis with GM-CSF (p < 0.0001). In studies planned to investigate whether
      susceptibility of treated cells to LAK activity was a consequence of a
      downregulation of adhesion molecules expressed on target cell surface, the
      proportion of cells expressing adhesion molecules was not significantly changed,
      except for CD54 expression on HL-60 cells which showed a higher expression, after
      cells were treated with RA or DMSO. We conclude that clonogenic cells are more
      sensitive to LAK cell lysis and that cell line sensitivity to LAK cytolysis can
      be modulated by a variety of agents of potential therapeutic use. The poor
      correlation between adhesion molecules expression and sensitivity to LAK lysis
      suggests that molecules other than CD54, CD56, CD58, and CD106 may possibly be
      more central to the processes involved.

PMID- 9517506
TI  - Elevated Bcl-2/Bax are a consistent feature of apoptosis resistance in B-cell
      chronic lymphocytic leukaemia and are correlated with in vivo chemoresistance.
AB  - We investigated the relationship between drug resistance and Bcl-2/Bax in B-cell
      chronic lymphocytic leukaemia (B-CLL). Apoptosis was induced in vitro with
      chlorambucil and cell death was monitored by dual-labelled FACS analysis using
      Annexin V and propidium iodide. Bcl-2 and Bax protein expression was quantified
      using FACS and a correlation between drug-induced apoptosis and Bcl-2/Bax was
      established. Cells were then sorted into viable and nonviable populations
      according to their forward and side-scatter characteristics and re-analysed for
      Bcl-2/Bax. The most resistant cells had elevated Bcl-2 levels and low Bax
      expression. Furthermore, those cells which were undergoing apoptosis showed only
      a marginal reduction in Bcl-2 expression, but significantly elevated Bax
      expression following exposure to chlorambucil. The Bcl-2/Bax was significantly
      greater in the cell fractions resistant to chlorambucil-induced apoptosis. This
      observation further supports the suggestion that Bax is the pivotal protein in
      determining the fate of cells following apoptotic signals.

PMID- 9517507
TI  - Cytogenetic and molecular biology for acute leukemias at diagnosis: a
      cost/effectiveness comparison.
AB  - This article presents a cost-effectiveness study comparing cytogenetic and
      molecular analyses for detection of chromosomal abnormalities which are
      prognostic factors in acute leukemia. The aim of the study was to determine how
      these two techniques could substitute or complement one another. The study sample
      consisted of 107 adult patients with de novo myeloid or lymphoid acute leukemias,
      tested by both techniques in 1994 and 1995, for identification of translocations
      t(9;22), t(8;21), t(15;17), t(4;11), t(1;19), the inversion of chromosome 16 and
      for monosomy 5 or 7 (or deletion of their long arms) and trisomy 8. The criterion
      for diagnostic effectiveness of these strategies was the rate of detection of
      true positive anomalies which are clinically relevant, according to the current
      state of knowledge. On the basis of these observations six alternative strategies
      at diagnosis were compared (each technique alone or different combinations of the
      two techniques). The study shows that:-for ALL, PCR alone appears the most cost
      effective strategy;-for AML, cytogenetic analysis alone is the best strategy;
      sequential strategies are more cost effective than simultaneous use of both
      techniques for minimising risk of false negatives.

PMID- 9517508
TI  - CECA-cyclophosphamide, etoposide, carboplatin and cytosine arabinoside--a new
      salvage regimen for relapsed or refractory acute myelogenous leukemia.
AB  - In an effort to develop more effective therapy for patients with refractory or
      relapsed acute myelogenous leukemia (R-AML) we combined three drugs with proven
      activity in AML, that are not typically used in induction regimens, with cytosine
      arabinoside (ara-C). Twenty-five patients (3 primary refractory, 22 relapsed)
      were treated. Patients received 3 days of "CECA" therapy as follows:
      cyclophosphamide (CTX) 1 g/m2 i.v. over 2 hrs., etoposide (VP-16) 200 mg/m2 i.v.
      over 3 hr, carboplatin (CBP) 150 mg/m2 i.v. over 24 hours and ara-C 1 g/m2 over 2
      hr. Peripheral circulating blasts cleared in 24 cases (96%), and marrow aplasia
      was achieved in 19 (76%). There were 3 complete remissions (CR), 1 patient died
      before day 14, 5 died aplastic 14 or more days from the start of therapy, 5 had
      primary resistant disease, and 10 had secondary resistance i.e., leukemia
      reappearing after developing aplasia and 1 was lost to follow up 6 weeks into
      therapy. Two of the patients achieving CR received allogeneic BMT in CR (at 18
      and 22 weeks): one died of fungal infection on day 50 and the other, who had CNS
      involvement at relapse, is alive 24 months post transplant. Toxicity was
      tolerable: one patient each developed grade III diarrhea and mucositis, another
      had grade III cardiac toxicity, a fourth developed a grade IV bilirubin
      elevation. Single, 2, and 3 or more infectious episodes occurred in 10, 5 and 4
      patients respectively. This regimen showed definite anti-leukemic activity: the 3
      patients achieving CR were among 23 patients with a 1%, 10% or 20% expectation
      for second CR attainment. The CECA regimen should be investigated in better
      prognosis salvage groups.

PMID- 9517509
TI  - Interleukin-4 and tumour necrosis factor-alpha produce non isotype specific
      partial differentiation of peripheral blood B-cells in myeloma.
AB  - In a previous study, culture of peripheral blood mononuclear cells (PBMC) from
      myeloma patients with interleukin(IL)-4 and tumour necrosis factor(TNF)-alpha
      resulted in the appearance of clonal plasma cells, thus suggesting the presence
      of circulating myeloma cell precursors in the peripheral blood. Using the same
      cytokine combination, we cultured PBMC and purified peripheral blood B-cells from
      myeloma patients. In nearly all cases, partial differentiation of B-cells
      occurred but, similarly to results for normal controls, both kappa and lambda
      light chain (L.C.) cytoplasmic positive lymphoid and lymphoplasmacytoid cells
      were detected rather than clonal plasma cells. These results suggest that IL-4
      and TNF-alpha cause partial differentiation of residual normal polyclonal B-cells
      rather than of circulating myeloma cell precursors in the peripheral blood of
      myeloma patients.

PMID- 9517510
TI  - Clinicopathological analysis of follicular lymphoma with a polyploid karyotype.
AB  - The prognostic significance of specific cytogenetic abnormalities in follicular
      lymphoma (FL) is an area of ongoing research. A small percentage of FL are
      characterized by a polyploid karyotype. Several studies have analyzed ploidy
      level to determine its role as an independent prognostic factor in non-Hodgkins
      lymphoma, with equivocal results, mostly using DNA flow cytometry to ascertain
      ploidy status. We have performed cytogenetic analyses on 180 cases of FL with a
      t(14;18) diagnosed between 1980 and 1995. Cases were divided into a polyploid
      group (20 cases) and a non-polyploid group (160 cases), polyploidy defined as a
      modal chromosome number of 58 or greater. Each group included examples of the 3
      subtypes of FL, [Working Formulation]: 1) follicular small cleaved cell (FSC), 2)
      follicular mixed, small and large cell (FM), and 3) follicular large cell (FLC).
      The median follow-up time was 38.5 months. The histological subclassification of
      the polyploid group revealed much less FSC (30% vs 66%, p < 0.004) and much more
      FLC (25% vs 4%, p < 0.003) than the non-polyploid group, implying histological
      progression may occur in parallel with the development of polyploidy. Recognized
      clinical prognostic factors were evenly distributed between the two groups and no
      survival difference was detected. We show that polyploidy as determined by
      classical cytogenetics is present in different frequencies across the subtypes of
      FL with a t(14;18), but is not an independent prognostic factor for survival in
      FL.

PMID- 9517511
TI  - Soluble L-selectin increases in the cerebrospinal fluid prior to meningeal
      involvement in children with acute lymphoblastic leukemia.
AB  - Soluble L-selectin was determined in the CSF samples of 20 children with CNS
      leukemia at the time they had blasts in CSF and/or clinical findings of CNS
      involvement; 17 CSF fluid samples were obtained from 17 of these 20 children, 29
      91 days before the appearance of CSF cytological and/or clinical findings of CNS
      involvement; while 15 CSF samples were withdrawn from among the same group of
      children, after treatment of meningeal leukemia. In addition, CSF sL-selectin was
      also assayed in 17 children with ALL, who remained in complete remission at least
      for a year and, as controls, in 12 children without malignant or meningeal
      disorders. There was no significant difference in CSF sL-selectin levels between
      the children with ALL without evidence of meningeal involvement and the controls
      (1.34 +/- 0.21 ng/ml, 1.46 +/- 0.18 ng/ml respectively, p > 0.05). However, in
      children with CNS leukemia, not only at the time CNS involvement was diagnosed,
      but also 29-91 days before the diagnosis of CNS leukemia, the concentrations of
      the CSF sL-selectin (12.41 +/- 2.14 ng/ml, 7.70 +/- 1.60 ng/ml respectively) were
      significantly higher than those in controls (p < 0.001 and p < 0.01
      respectively). After treatment and disappearance of the blasts in CSF, sL
      selectin was found to be decreased and even normalized in the majority of
      children who had meningeal involvement (2.87 +/- 2.14 ng/ml). In 5 children, the
      CSF sL-selectin remained high, after the blasts in CSF had disappeared and CNS
      leukemia recurred within 3 months in 4 of these 5 children. In conclusion, assay
      of sL-selectin in CSF seems to be a good diagnostic tool in the detection of CNS
      involvement in children with ALL. This method may also be used as an indicator,
      in prediction of the CNS leukemia, which is going to develop.

PMID- 9517512
TI  - L-selectin expression in CD34 positive cells in chronic myeloid leukemia.
AB  - L-selectin is a cell adhesion molecule, expressed on leukocytes and involved in
      the regulation of leukocyte traffic. This adhesion receptor is implicated in
      hematopoiesis by the interaction of hematopoietic stem cells and progenitors to
      stroma in the bone marrow microenvironment. We found that L-selectin expression
      on CD34++ cells from patients with chronic myelogenous leukemia (CML) is
      decreased or deficient, reflecting one of the features of malignant CML
      progenitors. In this review, we briefly describe the structure and function of L
      selectin, and its role in hematopoiesis and its expression in leukemia and
      lymphoma. Finally, we discuss the abnormal adhesiveness of CML progenitor cells,
      and the role of L-selectin in this defect.

PMID- 9517513
TI  - Subclinical alterations in coagulation and fibrinolysis in patients undergoing
      autologous peripheral blood stem cell transplantation.
AB  - We monitored 30 laboratory hemostatic parameters in an attempt to better
      comprehend alterations in coagulation and fibrinolysis in 10 patients with
      hematological malignancies subjected to autologous peripheral blood stem cell
      transplantation (APBSCT). These parameters were assessed before and just after
      high-dose conditioning chemotherapy, on days 1, 7, 14 and 28. Although, clinical
      manifestations associated with fibrino-coagulation disorders never occurred,
      including veno-occlusive disease, a statistically significant increase was seen
      in 7 of 30 parameters, compared to values seen before conditioning chemotherapy.
      These were subdivided into early and late phase parameters. The early phase
      parameters, which increased during the first day after the conditioning
      chemotherapy was given, then returned to baseline values, included protein C,
      plasma tissue factor and tissue-plasminogen activator. The late phase parameters,
      which increased over baseline values during days 7 to 28, included free-protein
      S, fibrinogen, plasmin-alpha2-plasmin inhibitor complex and soluble
      thrombomodulin. The increase of early phase parameters, as produced by the liver
      and by endothelial cells, may reflect tissue damage by conditioning chemotherapy.
      Late phase parameters increased in parallel with C-reactive protein, which
      suggests a correlation with the degree of inflammation, such as the presence of
      infective disease during neutropenia. These subclinical alterations in
      coagulation and fibrinolysis which take on a biphasic pattern during the course
      of APBSCT should be kept in mind by the attending physicians during therapy.

PMID- 9517514
TI  - t(2;5) positive lymphoma with peripheral blood involvement.
AB  - We report two cases of CD30 and t(2;5) positive lymphomas with peripheral blood
      (PB) involvement. Case one demonstrated the histological appearance of a diffuse
      large cell lymphoma with disease in the bone marrow (BM) and PB. Immunoperoxidase
      stains of the BM for CD30 proved to be of value in detecting disease. RT-PCR for
      the t(2;5) translocation product was positive in the PB, BM and lymph node. Case
      two had a typical anaplastic large cell lymphoma (ALCL) morphology, with a
      suboptimal BM biopsy, but abnormal circulating cells in the PB showing the
      presence of the NPM/ALK fusion product demonstrated by RT-PCR. The first case
      demonstrates that not all CD30 positive and t(2;5)-associated lymphomas have an
      anaplastic appearance. Routine staining for CD30 and EMA in BM biopsies is useful
      for pathological staging. The significance of the t(2;5) in defining a specific
      histological subtype is unclear. RT-PCR for the t(2;5) is a more sensitive test
      to detect disease in PB and BM as compared with light microscopy. The clinical
      significance of molecular staging for patients with ALCL using RT-PCR needs to be
      evaluated.

PMID- 9517515
TI  - Development of essential thrombocythemia in a patient treated with interferon
      alfa and pentostatin for hairy cell leukemia.
AB  - A patient is reported who developed essential thrombocythemia after successful
      treatment for hairy cell leukemia. He was initially treated with interferon alfa
      and subsequently relapsed within one year of treatment. His diagnosis was
      reconfirmed and then treated with Pentostatin. Six years after treatment he had a
      progressive increase in the platelet count and was diagnosed as essential
      thrombocythemia. Second cancers including various types of hematological
      malignancy have been reported in patients with hairy cell leukemia treated with
      chemotherapy or interferon alfa. These malignancies may represent either a new
      clonal disorder or a complication of drug treatment. This is the first report of
      a chronic myeloproliferative disorder following successful treatment of hairy
      cell leukemia.

PMID- 9517516
TI  - Fibrillary glomerulonephritis in Castleman's disease.
AB  - Castleman's disease is an uncommon lymph node disorder which can be associated
      with renal disease. In this report we describe a patient with fever, weight loss,
      anorexia, increase in inflammatory proteins, anemia and nephrotic syndrome.
      Castleman's disease, plasma cell type, was diagnosed by histologic analysis after
      surgical excision of a pelvic lymph node. The disease was considered localized,
      since further investigations did not show any other pathologic mass. After
      resection of the pelvic lymphoid mass, clinical remission of systemic symptoms
      and laboratory abnormalities was observed, with the exception of the nephrotic
      syndrome. Renal biopsy was performed and showed a pattern compatible with
      fibrillary glomerulonephritis. Progressive decline in renal function was
      observed, despite immunosuppressive therapy.

PMID- 9517517
TI  - Testicular plasmacytoma following chemical orchiectomy: potential role of
      hypogonadism in myeloma proliferation.
AB  - We present a case of a 55 year old man with multiple myeloma who underwent
      autologous stem cell transplantation and subsequently developed testicular
      myeloma. Testicular enlargement was observed only after treatment of an
      incidental prostatic adenocarcinoma with chemical orchidectomy at a time when
      myeloma was controlled systemically. A subsequent bilateral surgical orchiectomy
      revealed plasmacytoma in both testis. Enhanced production of B-lymphocytes after
      castration has been reported and implicates testosterone as a possible negative
      regulator of B-cell production. We propose that the androgen deficient state may
      have contributed to the development of plasmacytoma of the testes in our patient.
      The regulatory role of sex steroids in B-cell development is discussed.

PMID- 9517518
TI  - Hepatobiliary changes in patients with ulcerative colitis, with special reference
      to the effect of proctocolectomy.

PMID- 9517519
TI  - Different effects of white and red wine on lower esophageal sphincter pressure
      and gastroesophageal reflux.
AB  - BACKGROUND: White wine and beer induce gastroesophageal reflux (GER). We
      investigated the effects of white and red wine on lower esophageal sphincter
      pressure (LESP) and GER. METHODS: Twenty healthy volunteers received 300 ml white
      wine, red wine, or water together with a standardized meal. The LESP was
      continuously monitored with a Dent sleeve the 1st h postprandially, and the
      esophageal pH measured with a glass pH electrode. RESULTS: The LESP was decreased
      after intake of white wine (median, 14.9 mmHg; range, 5.6-19.5 mmHg) compared
      with red wine (20.4 mmHg; 13.1-22.3 mmHg; P < 0.05) and tap water (19.5 mmHg;
      16.2-29.1 mmHg; P < 0.01). The fraction time esophageal pH <4 was increased after
      both alcoholic beverages compared with tap water (0.9%; 0.2-5.8%; P < 0.01 versus
      white wine, P < 0.05 versus red wine) with a greater fraction time after white
      wine (13.2; 0.3-58.1 ) than after red wine (2.3; 0.7-24.4; P < 0.05). The
      decreased sphincter pressure after white wine was accompanied by a change in the
      reflux pattern with increased 'stress reflux' and the occurrence of 'free
      reflux'. CONCLUSION: White wine and red wine exert different effects on LESP and
      GER.

PMID- 9517521
TI  - The symptomatic effect of cisapride in patients with irritable bowel syndrome and
      constipation.
AB  - BACKGROUND: Cisapride improves symptoms in patients with idiopathic constipation.
      This trial compares the effect of cisapride with that of placebo in patients with
      irritable bowel syndrome (IBS) and constipation. METHODS: Seventy patients were
      randomized to 12 weeks' treatment with 5 mg cisapride three times daily or
      placebo in a double-blind trial. The dose could be doubled after 4 weeks in
      patients without satisfactory improvement. The patients scored their symptoms on
      a 100-mm visual analogue scale (VAS) (0 = best, 100 = worst), and the
      investigators evaluated the symptomatic effect. RESULTS: The dose was doubled in
      17 and 23 patients in the cisapride and placebo groups, respectively, after 4
      weeks. The patients' mean VAS score for global evaluation of IBS symptoms in the
      cisapride and placebo groups was 73 and 71 mm, respectively, at the start of
      treatment and 47 and 41 mm at the end. The difference between cisapride and
      placebo at the end was 6 mm in favour of placebo (95% confidence interval (CI), 
      6, 18) (NS). The investigators evaluated the effect as good or excellent in 39.2%
      and 58.8% in the cisapride and placebo groups, respectively. The difference in
      favour of placebo was 19.5% (95% CI, -5, 44) (NS). Nor were any statistically
      significant differences seen between cisapride and placebo in the other effect
      factors. CONCLUSIONS: The trial seems to exclude a clinically significant effect
      of 15-30 mg cisapride daily in patients with IBS and constipation during a 12
      week treatment period.

PMID- 9517520
TI  - Effect of mental stress and cisapride on autonomic nerve functions in functional
      dyspepsia.
AB  - BACKGROUND: Disordered autonomic nerve function is frequently present in patients
      with functional dyspepsia (FD). In this study we investigated whether the
      prokinetic cisapride, which acts via acetylcholine receptors, and stress may
      modulate these abnormalities. METHODS: Nineteen patients (6 men, 13 women) with
      FD and 10 healthy subjects (3 men, 7 women) were studied after 3 days' treatment
      with 10 mg cisapride three times daily and placebo in a crossover design. Mental
      stress was induced with a videogame. Sympathetic and vagal nerve functions were
      assessed noninvasively by skin conductance and respiratory sinus arrhythmia,
      respectively. RESULTS: Vagal tone was significantly lower in FD patients than in
      controls both before and after mental stress (P < 0.001). Sympathetic tone was
      higher in patients with FD than in controls (P < 0.03). Generally, stress scores
      were increased by mental stress in both groups (P < 0.001). In FD patients, but
      not in controls, cisapride significantly increased the sympathetic tone both
      before (P < 0.05) and after stress (P < 0.05). CONCLUSIONS: Patients with FD have
      lower vagal tone and higher sympathetic tone than healthy controls. Treatment
      with cisapride increased sympathetic tone in the patient group but had no effect
      on vagal tone.

PMID- 9517522
TI  - Failure to confirm association of vac A gene mosaicism with duodenal ulcer
      disease.
AB  - BACKGROUND: Mosaicism of the Helicobacter pylori vac A gene comprises two
      families of allelic variations of the signal sequence region (s1, s2) and of the
      mid-region (m1, m2). Initial studies suggested that peptic ulcer disease
      correlated with the s1 subtype of vac A. We compared the prevalence of various
      vac A genotypes of H. pylori isolates obtained from duodenal ulcer (DU) patients
      and subjects with simple gastritis. Those isolates with s1 type were further
      examined to determine whether the specific vac A s1 (s1a versus s1b) genotype
      enabled prediction of gastroduodenal disease. METHODS: H. pylori isolates were
      obtained from 38 patients with endoscopically documented DU and 39 individuals
      with asymptomatic H. pylori gastritis from Houston, Texas. The vac A genotype of
      each isolate was determined by polymerase chain reaction (PCR) amplification of
      genomic DNA for specific regions of the vac A gene. Those isolates with s1 vac A
      subtype were further examined to determine whether they had s1a or s1b mosaicism.
      RESULTS: There was no difference in frequency of the s1 genotype of isolates
      obtained from patients with duodenal ulcer or asymptomatic H. pylori gastritis in
      this sample (84% versus 79%, respectively; P = 0.77). The s1/m1 vac A genotype
      was detected in isolates from 16 duodenal ulcer patients versus 15 with H. pylori
      gastritis (P = 0.82). Detailed analysis of the s1 region failed to show a
      correlation of either s1a or s1b with duodenal ulcer. Both s1a and s1b genotypes
      were detected in 24 strains, and both m1 and m2 mid-gene PCR amplicons were seen
      in 16 strains. CONCLUSIONS: We were unable to use H. pylori vac A genotyping to
      predict type of gastroduodenal disease in our patient sample. This failure to
      confirm an association of vac A genotype and duodenal ulcer disease differs from
      samples from other regions. This most likely represents an example of differences
      in H. pylori strains infecting host populations in different geographic regions.
      This study confirms the importance of establishing statistical associations with
      isolates from widely separate geographic regions before concluding that disease
      related associations exist.

PMID- 9517523
TI  - Differing patterns of Helicobacter pylori gastritis in patients with duodenal,
      prepyloric, and gastric ulcer disease.
AB  - BACKGROUND: We investigated the risk relationship between histotopographic
      patterns of Helicobacter pylori gastritis and peptic ulcer site. METHODS: Three
      hundred and eighty-three infected patients were classified as having duodenal
      ulcer (n = 79), prepyloric ulcer (n = 39), gastric (angular) ulcer (n = 28), and
      no ulcer (n = 237). Antral and corpus biopsy specimens were taken. Sydney system
      based scores for bacterial density and activity and degree of gastritis were
      added to antral and corpus sum scores (SS) (range, 0-9). These were used to
      categorize the phenotype of gastritis. In addition, the presence or absence of
      mucosal atrophy was taken into account. The relative risk for ulcer association
      with these conditions was calculated. RESULTS: High-grade antral (SS > 5)
      associated with mild to moderate corpus (SS > 5) gastritis increased duodenal (RR
      = 4.9; confidence interval (CI), 2.8-8.5) and prepyloric ulcer risk (RR = 2.99;
      CI, 1.4-6.2). High-grade gastritis in the antrum (SS > 5) and corpus (SS > 5)
      increased gastric ulcer risk (RR = 3.7; CI, 1.6-8.3). Antral atrophy and/or
      intestinal metaplasia is associated with an increased gastric ulcer risk (RR =
      3.3; CI, 1.4-7.8). CONCLUSION: The pattern of H. pylori gastritis may define a
      risk for peptic ulcer at various sites, but additional factors, not reflected in
      histology, also contribute to this risk.

PMID- 9517525
TI  - Intestinal adaptation after massive proximal small-bowel resection in the pig.
AB  - BACKGROUND: Small-intestinal adaptation to resection has been extensively studied
      in rats. The present study investigates morphology, crypt cell proliferation, and
      disaccharidase activities of the remaining small intestine and colon after 75%
      proximal resection of porcine small intestine. METHODS: Specimens were obtained
      from the proximal jejunum, middle and distal ileum, and proximal colon
      preoperatively (n = 5) and 14 weeks after small-bowel transection (n = 5) or
      resection (n = 5). Proliferation was analyzed immunohistochemically with the Ki
      67 antigen MIB-1. Disaccharidase activities were determined in accordance with
      the method of Dahlqvist. RESULTS: In addition to macroscopic enlargement,
      resection markedly increased the villi and crypts of the remaining small bowel.
      Crypt cell proliferation decreased with advancing age after transection but
      remained at the preoperative level after resection. Specific, but not total,
      activities of maltase and sucrase in the mid-ileum decreased after resection.
      CONCLUSION: Small-intestinal adaptation in the pig involves macroscopic
      enlargement and a prompt increase in villus size, which is associated with high
      crypt cell proliferation.

PMID- 9517524
TI  - Epidermal growth factor and transforming growth factor alpha in duodenal ulcer
      and non-ulcer dyspepsia patients before and after Helicobacter pylori
      eradication.
AB  - BACKGROUND: Epidermal growth (EGF) and transforming growth factor alpha
      (TGFalpha) are potent gastric secretory inhibitors, mitogens, and mucosal
      protectors, but the impact of Helicobacter pylori infection on their mucosal
      expression and luminal release has not been clarified. METHODS: In this study,
      gene and immunoreactive and immunohistochemical expressions of EGF and TGFalpha
      were assessed in the gastric mucosa of 15 H. pylori-negative healthy normals, in
      22 H. pylori-positive duodenal ulcer patients (DU) and in 24 H. pylori-positive
      non-ulcer dyspepsia patients (NUD). All studies in DU and NUD patients were
      repeated after 2 weeks of triple therapy (amoxicillin + clarithromycin +
      omeprazole) and 4 weeks and 2 years later. RESULTS: Immunohistochemical
      expression of EGF and TGFalpha in H. pylori-positive DU and NUD was significantly
      higher than in H. pylori-negative normals, and this increase persisted at 2 and 4
      weeks after therapy but normalized 2 years later. EGF mRNA was detected in the
      gastric mucosa of H. pylori-positive DU before and at 2 and 4 weeks after H.
      pylori eradication, but it was not found 2 years after the eradication of H.
      pylori or in gastric mucosa of H. pylori-negative control subjects. TGFalpha mRNA
      was detected in the gastric mucosa independently of H. pylori status, with the
      stronger expression observed in the gastric mucosa of H. pylori-positive DU and
      NUD before eradication than after this procedure. Plasma gastrin, which was
      significantly increased in H. pylori-positive DU, normalized already after 2
      weeks of triple therapy. The eradication rate as determined by histology after
      triple therapy reached 86.3% in DU patients and 90.5% in NUD patients. Two years
      after the eradication the H. pylori reinfection rate was 4.5% among DU patients
      and 4.2% among NUD. Treatment of DU patients with triple therapy resulted in
      complete ulcer healing. CONCLUSIONS: 1) Chronic H. pylori infection and resulting
      antral gastritis are associated with increased plasma gastrin and increased
      mucosal cell proliferation, probably due to enhanced expression of EGF and
      TGFalpha, and 2) the H. pylori eradication results in a decrease in plasma
      gastrin, but the increase in gastric TGFalpha and EGF content is sustained,
      suggesting that they may be involved in ulcer healing.

PMID- 9517526
TI  - Efficacy of oral hyposmolar glucose-based and rice-based oral rehydration salt
      solutions in the treatment of cholera in adults.
AB  - BACKGROUND: Recent animal experiments and clinical trials have shown that both
      osmolarity and rice as the organic components are important factors for net
      intestinal absorption of an oral rehydration salt solution. METHODS: In a
      controlled clinical trial 123 male adult patients with severe cholera, after
      initial rehydration with intravenous Ringer's lactate solution, were randomly
      assigned to receive one of the four oral rehydration salt solutions: WHO ORS, ORS
      containing 70 mmol/l Na+ and 16.2 g/l glucose, rice ORS containing 50 g/l rice
      and 90 mmol/l Na+, and rice ORS containing 50 g/l rice and 70 mmol/l Na+. All
      patients received 300 mg of doxycycline as a single dose. RESULTS: Patients who
      received rice-low-sodium ORS subsequently had lower (P < 0.05) stool output, ORS
      consumption, and diarrhoea duration than the other three ORS groups. CONCLUSIONS:
      We conclude that rice-based low-sodium ORS is superior for treating adult
      cholera.

PMID- 9517527
TI  - Increased luminal nitric oxide in inflammatory bowel disease as shown with a
      novel minimally invasive method.
AB  - BACKGROUND: The production of nitric oxide (NO) is increased in ulcerative
      colitis, as shown by bioassays of NO synthase activity in mucosal biopsy
      specimens. We wanted to develop a less invasive method for measurement of NO
      directly in the rectum in patients with inflammatory bowel disease (IBD).
      METHODS: We studied 10 patients with active ulcerative colitis, 6 with active
      Crohn's disease, 6 with non-active ulcerative colitis, and 24 controls without
      inflammation A tonometer balloon catheter was inserted in the rectum and inflated
      with 5 ml of NO-free air. After 15 min of incubation the sample was extracted,
      and the NO concentration was immediately analysed with a chemiluminescence
      technique. RESULTS: Patients with active disease had greatly increased
      concentrations of NO in the rectum as compared with controls and patients with
      non-active disease. CONCLUSIONS: During inflammation in the large intestine
      increased amounts of NO are released from the mucosa. Measurements of NO directly
      in the rectum could be of help in further understanding the role of this gas in
      IBD. Moreover, it is tempting to speculate that this minimally invasive method
      could be clinically useful as a diagnostic tool and in monitoring the effect of
      therapy.

PMID- 9517528
TI  - Long-term observation of the perinuclear anti-neutrophil cytoplasmic antibody
      status in ulcerative colitis patients.
AB  - BACKGROUND: Perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA) have been
      regarded as a possible immunogenetic marker of ulcerative colitis. If this were
      true, the p-ANCA status of a given patient should be constant over time; however,
      little information is available on this issue. METHODS: One hundred and forty
      five sera collected from 40 ulcerative colitis patients during a mean follow-up
      period of 50.6 months were tested for p-ANCA reactivity by indirect
      immunofluorescence. RESULTS: At base line 24 patients (60%) were p-ANCA-positive,
      with no relationship to gender distribution, age at diagnosis, disease activity,
      or extension. During follow-up, changes in p-ANCA status occurred in 10 patients
      (25%). P-ANCA positivity during follow-up was associated with more aggressive
      forms of disease, whereas p-ANCA negativity was associated with stable remission.
      CONCLUSIONS: Changes in the p-ANCA status over time occur in some ulcerative
      colitis patients. P-ANCA behaviour is associated with different clinical patterns
      of disease.

PMID- 9517529
TI  - Oxazolone-induced colitis in rats: effects of budesonide, cyclosporin A, and 5
      aminosalicylic acid.
AB  - BACKGROUND: The intention of the present study was to develop a new hapten-based
      inflammatory bowel disease model in the rat, useful for pharmacologic screening
      of new substances with anti-inflammatory properties and immunomodulating
      capacities. It was considered important to avoid the use of an irritating barrier
      breaker, such as ethanol. METHODS: Dark Agouti rats were skin-sensitized with
      oxazolone and further challenged intra-rectally with oxazolone dissolved in
      carmellose sodium (Orabase)/peanut oil. The effects of treatment with budesonide,
      prednisolone, cyclosporin A, and 5-aminosalicylic acid (5-ASA) were studied.
      RESULTS: The intra-rectal challenge with oxazolone in sensitized rats induced an
      inflammation with an increased colon wet weight, pronounced myeloperoxidase (MPO)
      activity, and hyperemia/ulcerations in the epithelial lining. Improvement was
      achieved by treatment with budesonide, prednisolone, and cyclosporin A but not
      with 5-ASA. CONCLUSIONS: The model fulfills the criteria for a fast, reproducible
      animal model for human colon inflammation, suitable for pharmacologic screening
      and studies of an immune-driven colon inflammation.

PMID- 9517530
TI  - Insulin-like growth factor-I partially attenuates colonic damage in rats with
      experimental colitis induced by oral dextran sulphate sodium.
AB  - BACKGROUND: Administration of insulin-like growth factor-I (IGF-I) results in
      selective growth of the gastrointestinal tract. We investigated the effects of
      IGF-I on the colonic damage induced by oral dextran sulphate sodium (DSS) in the
      rat. METHODS: Rats consumed 2% DSS in the drinking water for 10 days to induce
      colitis. Pumps were implanted on day 3 to deliver IGF-I for 7 days. Colonic
      histopathology and immunolocalization of transforming growth factor-beta1 (TGF
      beta1) were assessed on day 10. RESULTS: Compared with the colon of vehicle
      treated rats consuming DSS, IGF-I increased the numbers of goblet cells by 76%,
      reduced the proportion of lamina propria cells expressing TGF-beta1, and reduced
      the thickness of submucosal and muscularis externa layers by 26% and 20%,
      respectively. CONCLUSIONS: We conclude that the effects of IGF-I treatment on the
      colonic epithelium may be mediated directly, whereas the reduced inflammation in
      the mucosa and submucosa may be mediated by a mechanism other than up-regulation
      of TGF-beta1-mediated immunosuppression.

PMID- 9517531
TI  - Comparison of nuclear matrix protein composition in colon cancer and dysplasia.
AB  - BACKGROUND: Abnormal nuclear morphology associated with cancer may reflect
      changes in the proteins of the nuclear matrix. METHODS: Nuclear matrix (NM)
      proteins were isolated from colonic tissue and analyzed by two-dimensional gel
      electrophoresis. RESULTS: Several matrix proteins that were found in ulcerative
      colitis (UC) dysplasia (n = 5) and/or UC cancer (n = 4) were not identified in
      normal colonic tissue. UC dysplasia tissue showed three specific NM proteins with
      molecular masses of 49.2 kDa, 20.0 kDa, and 19.0 kDa, whereas 29.0-kDa and 32.0
      kDa proteins were specific to UC cancer. Three proteins with 59.5-kDa (pI 6.3 and
      6.6) and 33.75-kDa (pI 7.5) masses were common to both dysplasia and cancer
      tissue. CONCLUSIONS: These data suggest that NM proteins may have a role in the
      transition of tissue towards the malignant phenotype.

PMID- 9517532
TI  - The effect of treatment with alpha-interferon on hepatitis G/GBV-C viraemia. The
      CONSTRUCT Group.
AB  - BACKGROUND: Hepatitis G virus (HGV) or GBV-C is frequently detected in patients
      co-infected with hepatitis C virus (HCV). This study investigated host and
      virologic factors influencing the response to HGV/GBV-C to alpha-interferon
      treatment. METHODS: HGV/GBV-C was detected and quantified by nested polymerase
      chain reaction. The influence of variables such as liver biopsy appearance, liver
      function abnormalities, and response of HCV to interferon treatment was
      monitored. RESULTS: Fourteen of the 25 HGV/GBV-C-infected patients treated with
      interferon (3-6 MIU three times a week for 6 months) became non-viraemic during
      treatment, although all relapsed after treatment withdrawal at 6 months, with no
      net change in virus load between 0 and 12 months. CONCLUSIONS: Predictive factors
      for clearance of HGV/GBV-C viraemia by interferon were pre-treatment severity of
      liver disease (median Knodell score of 4, compared with 7 for non-responders; P =
      0.030) and alanine aminotransferase levels (median, 114, 182 for non-responders;
      P = 0.039). Clearance was associated with the treatment response of HCV. Nine of
      13 who cleared HGV/GBV-C also cleared HCV, compared with 3 of 11 HGV/GBV-C non
      responders; P = 0.05). The shared susceptibility of HGV/GBV-C and HCV to
      interferon treatment suggests a link between the mechanism of clearance of the
      two viruses.

PMID- 9517533
TI  - Large intravenous bilirubin loads increase the cytotoxicity of bile and lower the
      resistance of the canalicular membrane to cytotoxic injury and cause cholestasis
      in pigs.
AB  - BACKGROUND: Large intravenous bilirubin loads cause loss of hepatic canalicular
      membrane microvilli and cholestasis. This study examines whether these untoward
      effects might be due to canalicular membrane injury from cytotoxic bile. METHODS:
      The cytotoxicity of bile was assayed against pig erythrocytes before and
      throughout 4.5-h intravenous infusion of 170 microg kg(-1) body weight of
      bilirubin in anaesthetized pigs. The capacity to generate canalicular bile flow
      was tested before and after bilirubin infusion by means of short-term intraportal
      cholic acid infusion. RESULTS: Bilirubin infusion increased the cytotoxicity of
      hepatic bile, reduced biliary phospholipid secretion by 90%, and caused
      cholestasis. Cholic acid infusion before bilirubin also increased the
      cytotoxicity of bile but increased bile flow and doubled biliary phospholipid
      output. CONCLUSION: Large intravenous bilirubin infusions increase the
      cytotoxicity of bile, suppress biliary phospholipid secretion, and render hepatic
      canalicular membrane microvilli susceptible to injury from cytotoxic bile so that
      cholestasis occurs.

PMID- 9517534
TI  - A scoring system for early differentiation of the etiology of acute pancreatitis.
AB  - BACKGROUND: The purpose of this study was to find a new scoring system for early
      differentiation between the two commonest etiologies of acute pancreatitis
      (biliary and alcoholic), because biliary pancreatitis can be treated early by
      endoscopic sphincterotomy, whereas such treatment is unnecessary in alcoholics.
      METHODS: One hundred and forty-five patients satisfied the requirements for
      participation in the study and were divided into groups A (alcoholic
      pancreatitis) and B (biliary pancreatitis). Seven variables (serum and urine
      amylase, aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT),
      alkaline phosphatase (ALP), lipase/amylase (L/A) ratio, and erythrocyte mean
      corpuscular volume (MCV)) that differed in a statistically significant manner
      between patients of the two groups were included in the scoring system. Each
      parameter was counted as 0 or 1 on the basis of its values, so the patients
      reached scores from 0 to 7. RESULTS: Scores > or =4 (P < 0.0001) were
      consistently present in biliary pancreatitis, whereas alcoholics scored <4, with
      a sensitivity of 92.04% and a specificity of 93.75%. CONCLUSIONS: Our new scoring
      system could be important in the early diagnosis of the etiology of acute
      pancreatitis in a manner that is non-invasive, easy to calculate, inexpensive,
      and readily available.

PMID- 9517535
TI  - Human immunodeficiency virus-related abdominal pain in South Africa. Aetiology,
      diagnosis and survival.
AB  - BACKGROUND: Abdominal pain in acquired immunodeficiency syndrome (AIDS) patients
      is often a marker of an underlying opportunistic pathologic condition. There are
      no data on HIV-related abdominal pain in Africa. METHODS: Forty-four consecutive
      Cape Town patients with advanced human immunodeficiency virus (HIV) infection
      (CD4 < 200) and abdominal pain were studied prospectively to determine aetiology
      and survival. RESULTS: A probable cause of pain was identified in 37 (84%):
      disseminated Mycobacterium tuberculosis infection in 11, cryptosporidiosis in 6,
      cytomegalovirus infection in 6, and atypical mycobacterial infection in 2.
      Gastrointestinal lymphoma and pancreatitis were not seen. Fever, hepatomegaly,
      respiratory symptoms, abnormal chest radiograph, and adenopathy, ascites, or
      abscesses on ultrasound had predictive diagnostic value for disseminated M.
      tuberculosis. Fifty-one per cent of abdominal pain patients survived 6 months,
      compared with 73% of all AIDS patients (P < 0.001). CONCLUSIONS: The aetiology of
      HIV-related abdominal pain in Cape Town reflects the high local prevalence of
      tuberculosis. Clinical and ultrasound features facilitate diagnosis. Abdominal
      pain is associated with poor survival.

PMID- 9517536
TI  - Metachronous small-bowel adenocarcinoma in coeliac disease: gluten-free diet is
      not protective.
AB  - Coeliac disease is associated with an increased risk of certain gastrointestinal
      malignancies, especially of the small bowel. Metachronous malignancies are well
      established in the colon, where adenocarcinoma is common, but are exceptional in
      the small intestine. We describe a young woman with a long history of
      malabsorption who was shown to have coeliac disease complicated by a small-bowel
      adenocarcinoma. The cancer was resected, and the coeliac disease went into
      complete remission on a strict gluten-free diet. Fifteen years later she
      developed iron deficiency anaemia. Investigations showed a metachronous small
      bowel adenocarcinoma but continuing remission of the coeliac disease. The case
      provides strong evidence against a causative role for the enteropathy of active
      coeliac disease in small-bowel adenocarcinoma and against a protective effect of
      a gluten-free diet in tumour development. Predisposition to adenocarcinoma in
      coeliac disease is probably genetic.

PMID- 9517537
TI  - Multiple time step diffusive Langevin dynamics for proteins.
AB  - We present an algorithm for simulating the long time scale dynamics of proteins
      and other macromolecules. Our method applies the concept of multiple time step
      integration to the diffusive Langevin equation, in which short time scale
      dynamics are replaced by friction and noise. The macromolecular force field is
      represented at atomic resolution. Slow motions are modeled by constrained
      Langevin dynamics with very large time steps, while faster degrees of freedom are
      kept in local thermal equilibrium. In the limit of a sufficiently large molecule,
      our algorithm is shown to reduce the CPU time required by two orders of
      magnitude. We test the algorithm on two systems, alanine dipeptide and bovine
      pancreatic trypsin inhibitor (BPTI), and find that it accurately calculates a
      variety of equilibrium and dynamical properties. In the case of BPTI, the CPU
      time required is reduced by nearly a factor of 60 compared to a conventional,
      unconstrained Langevin simulation using the same force field.

PMID- 9517538
TI  - Structural diversity of sequentially identical subsequences of proteins:
      identical octapeptides can have different conformations.
AB  - One of the most important questions in the protein folding problem is whether
      secondary structures are formed entirely by local interactions. One way to answer
      this question is to compare identical subsequences of proteins to see if they
      have identical structures. Such an exercise would also reveal a lower limit on
      the number of amino acids needed to form unique secondary structures. In this
      context, we have searched the April 1996 release of the Protein Data Bank for
      sequentially identical subsequences of proteins and compared their structures. We
      find that identical octamers can have different conformations. In addition, there
      are several examples of identical heptamers with different conformations, and the
      number of identical hexamers with different conformations has increased since the
      previous PDB releases. These observations imply that secondary structure can be
      formed entirely by non-local interactions and that an identical match of up to
      eight amino acids may not imply structural similarity. In addition to the larger
      context of the protein folding problem, these observations have implications for
      protein structure prediction methods.

PMID- 9517539
TI  - Full-matrix least-squares refinement of lysozymes and analysis of anisotropic
      thermal motion.
AB  - Crystal structures of turkey egg lysozyme (TEL) and human lysozyme (HL) were
      refined by full-matrix least-squares method using anisotropic temperature
      factors. The refinement converged at the conventional R-values of 0.104 (TEL) and
      0.115 (HL) for reflections with Fo > 0 to the resolution of 1.12 A and 1.15 A,
      respectively. The estimated r.m.s. coordinate errors for protein atoms were 0.031
      A (TEL) and 0.034 A (HL). The introduction of anisotropic temperature factors
      markedly reduced the R-value but did not significantly affect the main chain
      coordinates. The degree of anisotropy of atomic thermal motion has strong
      positive correlation with the square of distance from the molecular centroid. The
      ratio of the radial component of thermal ellipsoid to the r.m.s. magnitude of
      three principal components has negative correlation with the distance from the
      molecular centroid, suggesting the domination of libration rather than breathing
      motion. The TLS model was applied to elucidate the characteristics of the rigid
      body motion. The TLS tensors were determined by the least-squares fit to observed
      temperature factors. The profile of the magnitude of reproduced temperature
      factors by the TLS method well fitted to that of observed B(eqv). However,
      considerable disagreement was observed in the shape and orientation of thermal
      ellipsoid for atoms with large temperature factors, indicating the large
      contribution of local motion. The upper estimate of the external motion, 67%
      (TEL) and 61% (HL) of B(eqv), was deduced from the plot of the magnitude of TLS
      tensors determined for main chain atoms which were grouped into shells according
      to the distance from the center of libration. In the external motion, the
      translational portion is predominant and the contribution of libration and screw
      motion is relatively small. The internal motion, estimated by subtracting the
      upper estimate of the external motion from the observed temperature factor, is
      very similar between TEL and HL in spite of the difference in 54 of 130 amino
      acid residues and in crystal packing, being suggested to reflect the intrinsic
      internal motion of chicken-type lysozymes.

PMID- 9517540
TI  - Interaction potentials for protein folding.
AB  - We outline a general strategy for determining the effective coarse-grained
      interactions between the amino acids of a protein from the experimentally derived
      native-state structures. The method is, in principle, free from any adjustable or
      empirically determined parameters, and it is tested on simple models and compared
      with other existing approaches.

PMID- 9517541
TI  - Structural modeling of the complex between an acetylcholine receptor-mimicking
      antibody and its snake toxin antigen.
AB  - The antibody M alpha2-3 neutralizes the functional, acetylcholine receptor
      binding activity of its antigen, neurotoxin alpha, and exhibits several other
      properties in common with the receptor itself. We present here the results of
      calculations examining the three-dimensional structure of the toxin alpha:M
      alpha2-3 complex. The antigen structure, determined by nuclear magnetic resonance
      spectroscopy, was docked to models of the variable fragment of the antibody
      combining site by using a method based on surface complementarity and
      maximization of buried surface area while taking into account the possibility of
      conformational change on complexation. Extensive experimental information on the
      location of the functional epitope was incorporated into the analysis and used to
      screen candidate geometries of the complex resulting from the modeling. Eight
      plausible structures that are in accord with the experimental data were derived.
      Common structural features of the models are discussed, and residues of the
      antibody-combining site that are expected to play important roles in complexation
      are identified. In particular, three epitope residues that, according to
      mutagenesis experiments, make particularly strong contributions to the binding,
      interact excentrically and do not make contact with the central loops of the
      combining site, L3 and H3.

PMID- 9517542
TI  - Mapping the active site of factor Xa by selective inhibitors: an NMR and MD
      study.
AB  - The structure of two selective inhibitors, Ac-Tyr-Ile-Arg-Ile-Pro-NH2 and Ac-(4
      Amino-Phe)-(Cyclohexyl-Gly)-Arg-NH2, in the active site of the blood clotting
      enzyme factor Xa was determined by using transferred nuclear Overhauser effect
      nuclear magnetic resonance (NMR) spectroscopy. They represent a family of
      peptidic inhibitors obtained by the screening of a vast combinatorial library.
      Each structure was first calculated by using standard computational procedures
      (distance geometry, simulated annealing, energy minimization) and then further
      refined by systematic search of the conformation of the inhibitor docked in the
      active site and repeating the simulated annealing and energy minimization. The
      final structure was optimized by molecular dynamics simulations of the inhibitor
      complex in water. The NMR restraints were kept throughout the refinement. The
      inhibitors assume a compact, very well defined conformation, embedded into the
      substrate binding site not in the same way as a substrate, blocking thus the
      catalysis. The model allows to explain the mode of action, affinity, and
      specificity of the peptides and to map the active site.

PMID- 9517544
TI  - Tertiary structure prediction of the KIX domain of CBP using Monte Carlo
      simulations driven by restraints derived from multiple sequence alignments.
AB  - Using a recently developed protein folding algorithm, a prediction of the
      tertiary structure of the KIX domain of the CREB binding protein is described.
      The method incorporates predicted secondary and tertiary restraints derived from
      multiple sequence alignments in a reduced protein model whose conformational
      space is explored by Monte Carlo dynamics. Secondary structure restraints are
      provided by the PHD secondary structure prediction algorithm that was modified
      for the presence of predicted U-turns, i.e., regions where the chain reverses
      global direction. Tertiary restraints are obtained via a two-step process: First,
      seed side-chain contacts are identified from a correlated mutation analysis, and
      then, a threading-based algorithm expands the number of these seed contacts.
      Blind predictions indicate that the KIX domain is a putative three-helix bundle,
      although the chirality of the bundle could not be uniquely determined. The
      expected root-mean-square deviation for the correct chirality of the KIX domain
      is between 5.0 and 6.2 A. This is to be compared with the estimate of 12.9 A that
      would be expected by a random prediction, using the model of F. Cohen and M.
      Sternberg (J. Mol. Biol. 138:321-333, 1980).

PMID- 9517543
TI  - A model for the nucleotide-binding domains of ABC transporters based on the large
      domain of aspartate aminotransferase.
AB  - ABC transporters are a large superfamily of integral membrane proteins involved
      inATP-dependent transport across biological membranes. Members of this
      superfamily play roles in a number of phenomena of biomedical interest, including
      cystic fibrosis (CFTR) and multidrug resistance (P-glycoprotein, MRP). Most ABC
      transporters are predicted to consist of four domains, two membrane-spanning
      domains and two cytoplasmic domains. The latter contain conserved nucleotide
      binding motifs. Attempts to determine the structure of ABC transporters and of
      their separate domains are in progress but have not yet been successful. To aid
      structure determination and possibly learn more about the domain boundaries, we
      set out to model nucleotide-binding domains (NBDs) of ABC transporters based on a
      known structure. Previous attempts to predict the 3D structure of NBDs were based
      solely on sequence similarity with known nucleotide-binding folds. We have
      analyzed the sequences of a number of nucleotide-binding domains with the
      algorithm THREADER, developed by D.T. Jones, and a possible fold was found in the
      structure of aspartate aminotransferase. We present a model for the N-terminal
      NBD of CFTR, based on the large domain of the A chain of aspartate
      aminotransferase. The model is refined using multiple sequence alignment,
      secondary structure prediction, and 3D-1D profiles. Our model seems to be in good
      agreement with known properties of nucleotide-binding domains and has some
      appealing characteristics compared with the previous models.

PMID- 9517545
TI  - Two structural subdomains of barstar detected by rapid mixing NMR measurement of
      amide hydrogen exchange.
AB  - Equilibrium amide hydrogen exchange studies of barstar have been carried out at
      pH 6.7, 32 degrees C using one- and two-dimensional nuclear magnetic resonance.
      An unusually large fraction of the backbone amide hydrogens of barstar exchange
      too fast to be measured, and the exchange rates of only fifteen slow-exchanging
      amide sites including indole amides of two tryptophans could be measured in the
      presence of 0 to 1.8 M guanidine hydrochloride (GdnHCl). Measurement of exchange
      occurring in tens of seconds in the unfolding transition region was possible by
      the use of a fast stopped-flow mixing method. The observed exchange rates have
      been simulated in the EX2 limit according to a two-process model that
      incorporates two exchange-competent states: a transiently unfolded state (U*) in
      which many amide hydrogens are completely accessible to solvent-exchange, and a
      near-native locally unfolded state (N*), in which only one or a few amide
      hydrogens are completely accessible to solvent-exchange. The two-process model
      appears to account for the observed exchange behavior over the entire range of
      GdnHCl concentrations studied. For several measurable slow-exchanging amide
      hydrogens, the free energies of production of exchange-competent states from the
      exchange-incompetent native state are significantly higher than the free-energy
      of production of the equilibrium unfolded state from the native state, when the
      latter is determined from circular dichroism- or fluorescence-monitored
      equilibrium unfolding curves. The result implies that U*, which forms transiently
      in the strongly native-like conditions used for the hydrogen exchange studies, is
      higher in energy than the equilibrium-unfolded state. The higher energy of this
      transiently unfolded exchange-competent state can be attributed to either proline
      isomerization or to the presence of residual structure. On the basis of the free
      energies of production of exchange-competent states, the measured amide sites of
      barstar appear to define two structural subdomains--a three-helix unit and a two
      beta-strand unit in the core of the protein.

PMID- 9517546
TI  - Conformation of the sebacyl beta1Lys82-beta2Lys82 crosslink in T-state human
      hemoglobin.
AB  - The crystal structure of human T state hemoglobin crosslinked with bis(3,5
      dibromo-salicyl) sebacate has been determined at 1.9 A resolution. The final
      crystallographic R factor is 0.168 with root-mean-square deviations (RMSD) from
      ideal bond distance of 0.018 A. The 10-carbon sebacyl residue found in the beta
      cleft covalently links the two betaLys82 residues. The sebacyl residue assumes a
      zigzag conformation with cis amide bonds formed by the NZ atoms of betaLys82's
      and the sebacyl carbonyl oxygens. The atoms of the crosslink have an occupancy
      factor of 1.0 with an average temperature factor for all atoms of 34 A2. An RMSD
      of 0.27 for all CA's of the tetramer is observed when the crosslinked
      deoxyhemoglobin is compared with deoxyhemoglobin refined by using a similar
      protocol, 2HHD [Fronticelli et al. J. Biol. Chem. 269: 23965-23969, 1994]. Thus,
      no significant perturbations in the tertiary or quaternary structure are
      introduced by the presence of the sebacyl residue. However, the sebacyl residue
      does displace seven water molecules in the beta cleft and the conformations of
      the beta1Lys82 and beta2Lys82 are altered because of the crosslinking. The
      carbonyl oxygen that is part of the amide bond formed with the NZ of beta2Lys82
      forms a hydrogen bond with side chain of beta2Asn139 that is in turn hydrogen
      bonded to the side chain of beta2Arg104. A comparison of the observed
      conformation with that modeled [Bucci et al. Biochemistry 35:3418-3425, 1996]
      shows significant differences. The differences in the structures can be
      rationalized in terms of compensating changes in the estimated free-energy
      balance, based on differences in exposed surface areas and the observed shift in
      the side-chain hydrogen-bonding pattern involving beta2Arg104, beta2Asn139, and
      the associated sebacyl carbonyl group.

PMID- 9517547
TI  - Characterization of receptors with a new negative image: use in molecular docking
      and lead optimization.
AB  - The characterization of receptor binding sites is an important aspect of
      molecular docking, molecular recognition, and the structure-based design process.
      This characterization can take several forms: the receptor surface itself can be
      delineated or described, the space adjacent to the surface can be chemically
      mapped, or a negative image of the protein binding region can be generated. In
      this report, we describe a new method of constructing a negative image through
      generation of a set of spheres. These spheres lie along the receptor surface, and
      their centers represent possible ligand atom positions. By the method in which
      they are constructed, these spheres carry a limited amount of energetic and
      chemical information in addition to their primary geometric information. We test
      the accuracy of the image by comparing sphere positions to the positions of bound
      ligand atoms and propose a figure of merit for such tests. Then, we use the
      spheres to orient ligands in enzyme active sites and show how they can be used to
      generate low scoring configurations more efficiently than other approaches that
      search orientation space. In addition, two novel applications of these spheres
      are described: they are used to help identify structural differences among
      families of enzymes and to suggest points for ligand modification in analog
      design.

PMID- 9517548
TI  - Amplitudes, durations, and timings of apically directed left ventricular
      myocardial velocities: I. Their normal pattern and coupling to ventricular
      filling and ejection.
AB  - BACKGROUND: The left ventricular (LV) major axis shortening is an important
      determinant of its global function. But unlike the LV minor axis dynamics, the
      long-axis dynamics have not been well characterized. We investigated the
      amplitudes, durations, and timings of LV long-axis myocardial velocities and
      related them to LV filling and ejection in normal healthy volunteers. METHODS AND
      RESULTS: Myocardial velocities from the basal, mid, and distal portions of the
      four LV walls were recorded from the apical window with spectral Doppler tissue
      imaging in 20 normal individuals. The timings, amplitudes, and durations were
      measured and compared both longitudinally and circumferentially. These were also
      related to mitral inflow and LV ejection. Analysis of the recordings indicated
      that there were three principal myocardial velocities: apically directed systolic
      velocity and atrially directed early and late diastolic velocities. The LV
      posterior wall had the highest shortening velocity and the amount of shortening.
      The lateral wall had the greatest amplitude of early diastolic lengthening
      velocity, amount of lengthening, and early to late lengthening velocity and
      integral ratios, probably indicating most favorable early diastolic properties.
      There was a striking synchrony in the myocardial velocities circumferentially.
      The myocardial velocities dropped progressively as the sampling site was moved
      distally and the LV apex was practically stationary. Although the onsets of the
      velocity profiles were simultaneous in the meridional orientation, their
      durations were shorter distally. All myocardial velocities preceded the
      corresponding blood flow velocities. They also ended before the corresponding
      blood flow velocities, this being more pronounced in the distal myocardial
      segments, indicating the presence of inertial factors responsible for the
      terminal portions of mitral and aortic flows. CONCLUSIONS: Recording of apically
      directed myocardial velocities gives valuable insights into the regional
      myocardial function. These velocities show significant regional variations in
      healthy normal individuals. It is speculated that analysis of regional myocardial
      velocities may have a role in the diagnosis of early myocardial disease.

PMID- 9517549
TI  - Amplitudes, durations, and timings of apically directed left ventricular
      myocardial velocities: II. Systolic and diastolic asynchrony in patients with
      left ventricular hypertrophy.
AB  - BACKGROUND: Regional myocardial dysfunction may be the earliest manifestation of
      myocardial disease and can occur in the absence of abnormalities of global left
      ventricular (LV) function. The LV long-axis function, which is mainly due to
      subendocardial muscle fibers, may become abnormal in the presence of normal short
      axis function. This study investigates the temporal and spatial characteristics
      of the LV long-axis function in patients with secondary LV hypertrophy in the
      presence of normal systolic function. METHODS AND RESULTS: LV long-axis
      myocardial velocities were recorded in 18 patients with LV hypertrophy and
      preserved regional and global systolic function with Doppler tissue imaging.
      Apically directed myocardial velocities were recorded from the basal, mid, and
      apical segments of the four LV walls, and their amplitudes, timings, and
      durations were measured. The abnormalities uncovered by the analysis of regional
      myocardial velocities included (1) asynchrony in the onset of myocardial
      contraction circumferentially, (2) presence of postejection LV shortening, (3)
      asynchrony in the onset of early myocardial lengthening circumferentially, (4)
      reduced early myocardial lengthening velocity, (5) reduced early to late
      myocardial lengthening velocity and extents circumferentially, and (6) lack of
      variation in the basal myocardial velocities circumferentially in contrast to
      normal individuals. CONCLUSIONS: Patients with secondary LV hypertrophy with
      preserved regional and global systolic performance have distinct abnormalities in
      the timings and amplitudes of apically directed myocardial velocities. These
      abnormalities may explain some of the changes in LV global diastolic behavior and
      may also serve as markers of early regional myocardial dysfunction.

PMID- 9517550
TI  - Early diastolic intraventricular filling pattern in acute myocardial infarction
      by color M-mode Doppler echocardiography.
AB  - The aim of the present study was to investigate whether slowing of mitral-to
      apical filling is present in patients with acute myocardial infarction (AMI).
      Twenty-eight patients with their first AMI were examined by color M-mode Doppler
      echocardiography. Twenty-eight age- and sex-matched healthy individuals served as
      control subjects. From the color M-mode Doppler images, we measured the time
      difference (TD) between occurrence of peak flow velocity at the mitral tip and in
      the apical region by a blinded analysis. The TD was increased in the AMI group
      compared with the control subjects (70 +/- 60 versus 40 +/- 30 msec, p = 0.02)
      and correlated with peak SGOT (r = 0.46, p = 0.02) and age (r = 0.57, p < 0.01).
      In the 15 patients with anterior AMI, the correlation between TD and SGOT was
      better (r = 0.68, p < 0.01). This study demonstrated slowing of early diastolic
      mitral-to-apical flow propagation in patients with AMI. Infarction size and age
      appear to be of importance for the retardation of mitral-to-apical flow
      propagation.

PMID- 9517553
TI  - Rapid estimation of regurgitant volume by the proximal isovelocity surface area
      method in mitral regurgitation: Can continuous-wave Doppler echocardiography be
      omitted?
AB  - The proximal isovelocity surface area (PISA) method is accurate for quantitating
      mitral regurgitation but requires recording both mitral maximal and integrated
      jet velocities using the same continuous-wave Doppler jet signal. In 272
      consecutive patients with isolated mitral regurgitation, the mean ratio of
      maximal to integral of velocity had a narrow range of variation (mean +/- SD,
      3.25 +/- 0.47). The estimated regurgitant volume, calculated as regurgitant
      flow/3.25, showed an excellent correlation with reference regurgitant volumes (r
      = 0.96 and r = 0.97; standard error of the estimate, 11 ml; both p < 0.0001),
      with limited overestimation and high sensitivity and specificity for severe
      mitral regurgitation. The estimated regurgitant volume is a useful measurement in
      patients in whom the continuous-wave Doppler signal of mitral regurgitation
      cannot be obtained.

PMID- 9517551
TI  - Accurate noninvasive estimation of left ventricular end-diastolic pressure:
      comparison with catheterization.
AB  - We evaluated the accuracy of a new Doppler-based method using the mitral
      regurgitant velocity at the time of aortic valve opening for the noninvasive
      estimation of left ventricular end-diastolic pressure. Sixty unselected patients
      were studied immediately before routine catheterization. Invasive left
      ventricular end-diastolic pressure was obtained using a fluid-filled pig-tail
      catheter. Noninvasive estimation of left ventricular pressure at aortic valve
      opening was taken as systemic diastolic pressure using an automated cuff.
      Noninvasive left ventricular end-diastolic pressure was calculated as diastolic
      blood pressure--4 x (mitral regurgitant velocity at aortic opening)2. Those
      making noninvasive determinations were blinded to catheterization results. An
      adequate mitral regurgitant Doppler recording was obtained in 24 patients (40%).
      In patients with a left ventricular end-diastolic pressure greater than 15 mm Hg
      the yield was 65%. Left ventricular end-diastolic pressures ranged from 4 mm Hg
      to 30 mm Hg. Bland and Altman analysis revealed no systematic bias and close
      agreement was found, with individual discrepancies not exceeding 5 mm Hg.

PMID- 9517552
TI  - Pulmonary venous flow Doppler velocities in children.
AB  - We report the results of a prospective study of pulmonary venous (PV) flow
      Doppler velocities in 68 normal children. We sought to establish the normal PV
      flow velocities in the broad pediatric population, compare these velocities to
      heart rate and age. In normal children, there is a wide range of PV flow
      velocities, most of which correlate with age and heart rate. However, the PV flow
      velocities and their durations do not distinguish the age groups. The peak
      velocity of systolic forward flow and atrial reversal flow in the pulmonary vein
      were independent of heart rate. The PV flow peak systolic velocity showed a weak
      correlation with the velocity of the mitral inflow early wave. However, the
      velocity of atrial reversal flow showed no correlation with the mitral inflow A
      velocity (late wave), which is generated by the same force of atrial contraction.

PMID- 9517554
TI  - Echocardiographic quantitation of mitral regurgitation: a new Doppler technique.
AB  - Our objective is to develop a new transthoracic Doppler echocardiographic
      technique to determine mitral regurgitant fraction. The standard color Doppler
      method for assessment of mitral regurgitation is semiquantitative and dependent
      on instrument gain. By using the mitral and aortic valve continuous wave Doppler
      velocities, one can determine regurgitant fraction. This technique takes into
      account the flow dependence of the mitral valve area. Two constants, A and B,
      which represent the flow dependence of the mitral valve area and the ratio of the
      mitral valve area to aortic valve area at zero flow, respectively, were
      determined by regression in 36 patients without valvular disease (r = .89).
      Thirty patients with isolated mitral regurgitation were then studied. The mitral
      regurgitant fraction was calculated from the following: Regurgitant fraction = 1 
      TVIav/Bf[Vmv/(1 - AVmv)]dt, where TVIav is the time velocity integral across the
      aortic valve, Vmv is the continuous wave velocity across the mitral valve, and A
      and B are constants. The regurgitant fraction was then compared with color
      Doppler assessment of mitral regurgitation assessed by independent observers. In
      patients with mitral regurgitation, there was a strong correlation between
      standard visual assessment and our new Doppler method (Kendall's tau b rank
      correlation = 0.65; p < .001). The new Doppler method was able to correctly
      categorize 90% of patients with mild mitral regurgitation and 88% of patients
      with severe mitral regurgitation; however, there was poorer agreement with the
      color Doppler assessment of moderate mitral regurgitation. Mitral regurgitant
      fraction can be calculated with our new Doppler method. This method is
      quantitative, objective, nongain dependent, and separates mild from severe mitral
      regurgitation well.

PMID- 9517555
TI  - Methods for quantifying ultrasound backscatter and two-dimensional video
      intensity: implications for contrast-enhanced sonography.
AB  - Quantification of acoustic backscatter energy is believed to be useful for
      assessing "tissue character" and for quantifying the regional concentration of
      echo contrast. Measurement of ultrasonic video intensity has been the traditional
      means of quantifying backscatter energy, with "integrated backscatter" considered
      the gold standard. The purpose of this work is to review the commonly used
      methods for quantifying ultrasonic backscatter and to describe the difference
      between detected backscatter energy and the intrinsic tissue backscatter
      coefficient. Many of the quantification pitfalls that can lead to erroneous
      conclusions will also be discussed. A set of eight rubber phantoms with
      backscatter coefficient from -6 dB to +15 dB relative to liver were imaged at
      2.5, 3.5, and 5.0 MHz. Methods for calculating the acoustic backscatter intensity
      from calibrated video intensity measurements and for calculating the tissue
      backscatter coefficient are described and tested using equipment from two
      different manufacturers. A commercially available automatic "acoustic
      densitometry" system with on-board quantitative integrated backscatter is also
      evaluated. Ultrasound attenuation and ultrasound system factors were found to
      strongly influence the detected backscatter intensity using either calibrated
      video intensity or on-board integrated backscatter. Special system transfer
      functions and attenuation correction were found to be useful in converting video
      intensity and integrated backscatter to a measure of the intrinsic tissue
      backscatter coefficient. With these correction factors, the correlation between
      the measured tissue backscatter coefficient and the phantom backscatter
      coefficient was excellent (r = 0.99, intercept 0.0, regression slope essentially
      1.0) at all three imaging frequencies with traditional video intensity or on
      board integrated backscatter. Uncalibrated video intensity and on-board
      integrated backscatter have limitations when used in isolation for tissue
      characterization. Rigorous attention to the imaging parameters and the use of
      calibration functions are necessary before video intensity measurement or
      integrated backscatter can be used reliably to measure the tissue backscatter
      coefficient.

PMID- 9517556
TI  - Detection of perfusion defects during coronary occlusion and myocardial
      reperfusion after thrombolysis by intravenous administration of the echo
      enhancing agent BR1.
AB  - The purpose of this study was to detect myocardial perfusion defects as a result
      of coronary occlusion and myocardial reperfusion after thrombolysis with
      intravenous (i.v.) administration of the echo contrast agent BR1 (Bracco
      Research, Switzerland), which consists of microbubbles (median diameter 2.5
      microm) containing sulfur exafluoride in a phospholipidic shell. To generate a
      coronary thrombosis, a copper coil was advanced into the left circumflex coronary
      artery in eight anesthetized dogs with opened chest cavities. Coronary occlusion
      occurred 18 +/- 10 minutes after the insertion of the coil and was documented
      both by an electromagnetic flow meter (as zero blood flow) and by radiolabeled
      microspheres (as myocardial perfusion defect). After 2 hours of occlusion,
      streptokinase was infused i.v.; reperfusion was documented by both the flow-meter
      and microspheres. Left ventricular cavity enhancement was apparent after all
      contrast injections. Peak cavity intensity did not increase with dose and was not
      affected by signal processing (suggesting signal saturation), whereas the
      duration of contrast effect significantly increased with the dose (from 26 +/- 16
      to 147 +/- 74 seconds). Myocardial contrast intensity also increased after
      contrast (from 15 +/- 12 to 21 +/- 18 gray level/pixel, p < 0.001). Contrast echo
      detected myocardial perfusion defects (corresponding to 17% +/- 11% of LV cross
      sectional area) in all the injections performed during coronary occlusion and
      detected myocardial reperfusion with a sensitivity of 50% versus microspheres.
      The extent of perfusion defects by contrast echo showed a good correlation with
      microspheres (r = 0.73). Myocardial reperfusion was not detected by changes in
      heart rate, aortic pressure, pulmonary arterial pressure, cardiac output, left
      ventricular fractional area change, or wall-motion score index. Hemodynamic
      parameters were not affected by contrast injections. Thus, the i.v.
      administration of BR1 allows us to accurately detect myocardial perfusion defects
      during coronary occlusion and, to a lesser extent, myocardial reperfusion after
      thrombolysis.

PMID- 9517558
TI  - Three-dimensional measurement of the mitral annulus by multiplane transesophageal
      echocardiography: in vitro validation and in vivo demonstration.
AB  - Ten phantoms were scanned with a multiplane transesophageal echocardiographic
      probe in a water bath to assess a new method for three-dimensional modeling of
      the mitral annulus. The annulus was reconstructed from manually outlined borders
      with Fourier series in each of the three spatial coordinates. Comparisons with
      direct measurements by least-squares linear regression gave coefficients of
      determination of 0.99 for annular height, area, and circumference. Expressed as a
      percentage of their true values, the mean +/- SD of the errors were -0.1% +/-
      3.0% for annular height, -2.8% +/- 3.1% for area, and -0.2% +/- 1.7% for
      circumference. The mean residual error length for phantoms was 0.64 mm compared
      with 1.21 mm in nine patients studied during general anesthesia. This method
      gives accurate and precise measurements of the mitral annulus in vitro and should
      be valuable for studying its morphology and dynamics in vivo.

PMID- 9517557
TI  - Does dobutamine stress echocardiography induce damage during viability diagnosis
      of patients with chronic regional dysfunction after myocardial infarction?
AB  - Experimental hibernating-model investigations of animals have shown that
      myocardial necrosis can be induced by longer-term intracoronary dobutamine
      infusion. This study was designed to determine whether myocardial infarction
      could be ascertained in patients with chronic regional wall motion abnormalities
      and greater than 75% stenosis in the supplying coronary artery through dobutamine
      stress echocardiography. Twenty patients with coronary artery disease and
      regional resting wall motion abnormalities were examined with a standard
      dobutamine protocol (5 to 50 microg/kg/min). Exclusion criteria were an acute
      coronary syndrome, severe heart failure, and severe hypertension. Creatine kinase
      (CK, CKMB), myoglobin, and troponine-I were measured before and at each of the
      first 7 hours after beginning of infusion. Fourteen of these 20 patients
      exhibited viable myocardium. The serum markers CK, CKMB, myoglobin, and troponin
      I demonstrated no increase beyond the reference range, suggesting that with this
      protocol, no myocardial necrosis was induced.

PMID- 9517560
TI  - Membranous subaortic stenosis presenting decades after surgical correction for
      tetralogy of Fallot.
AB  - Subaortic stenosis is rare in the middle-aged adult. Its association with
      tetralogy of Fallot is extremely rare. We report two middle-aged patients,
      presenting three decades after surgical repair of tetralogy of Fallot, with the
      rare association of subaortic stenosis. The clinical presentation in each patient
      mimicked residual pulmonary stenosis and insufficiency, but echocardiography
      revealed subaortic stenosis with associated valvular aortic regurgitation.

PMID- 9517559
TI  - Transesophageal ultrasonographic imaging in rat hearts: visualization of aortic
      valve vegetations in non-bacterial thrombotic endocarditis.
AB  - The aim of this study was to test the feasibility of transesophageal
      ultrasonography in rats by using an intravascular ultrasound system for
      visualization of vegetations at the aortic valve in the animal model of
      experimental endocarditis. After anesthesia and preparation of the right carotid
      artery, a polyethylene catheter was advanced across the aortic valve into the
      left ventricle in 91 rats. For transesophageal ultrasonography an intravascular
      ultrasound catheter (3.5 French; 30 MHz) linked to an imaging system was
      introduced into the esophagus. Sonographic investigations were performed every 24
      hours until death. The presence, size, and echogenicity of vegetations were
      evaluated. Presence and size were compared to autopsy findings. No complications
      occurred as a result of the sonographic investigation. Left-sided valvular
      structures were imaged regularly. For detection of vegetations, sensitivity and
      specificity were 93% and 88%, respectively. Comparing the measurements of the
      vegetation size the following regression equation was obtained: y = 0.74x + 0.04
      (r = 0.89; standard error of estimate = 0.02 cm). Inter- and intraobserver
      variabilities for sonographic measurements were 8.3% and 6.2%, respectively.
      Transesophageal ultrasonography permits reliable detection and repetitive
      accurate quantification of vegetations in the rat model of endocarditis. The
      technique enhances longitudinal studies of the dynamic process of the growth of
      vegetations under defined microbial conditions.

PMID- 9517561
TI  - Spontaneous resolution of pulmonary venous thrombosis after lung transplantation.
AB  - Thrombus formation at the pulmonary venous anastomotic site after lung
      transplantation may have catastrophic consequences, including allograft failure
      and stroke. However, treatment with systemic anticoagulation may facilitate
      bleeding in the early postoperative period. In the present report, we describe
      the clinical and transesophageal echocardiographic findings of pulmonary venous
      thrombosis in two patients in the immediate postoperative period after lung
      transplantation. Treatment with systemic anticoagulation was not feasible because
      of extensive postoperative thoracic bleeding in each instance. A conservative
      approach was taken on the basis of the small size of each thrombus and lack of
      accelerated flow velocity at the site of the thrombus. Each thrombus resolved
      spontaneously without clinical sequelae. These two cases suggest that thrombus
      size and flow velocity at the anastomotic site may be used to guide the clinical
      management of pulmonary venous thrombosis after lung transplantation.

PMID- 9517562
TI  - Large pulmonary vein varix diagnosed by transesophageal echocardiography: an
      unusual site for thrombus in atrial fibrillation.
AB  - An elderly man with pulmonary vein varix and atrial fibrillation is described.
      The diagnosis of pulmonary varix, a localized dilatation of pulmonary vein, was
      made by transesophageal echocardiography. The patient had chronic atrial
      fibrillation, and transesophageal echocardiography demonstrated thrombus in the
      pulmonary varix. In patients with atrial fibrillation, pulmonary varix may be an
      unusual site for thrombus formation.

PMID- 9517563
TI  - Primary mycotic aneurysm of the ascending aorta diagnosed by transesophageal
      echocardiography.
AB  - Primary mycotic aneurysms are rare, and they can be difficult to diagnose before
      rupture. Early diagnosis is the cornerstone to effective management. Preoperative
      diagnosis has traditionally involved angiography and computed tomography. We
      report a case of Staphylococcus aureus aortitis with an aortic wall abscess and
      posterior pseudoaneurysm formation involving the ascending aorta in which
      transesophageal echocardiography was fundamental in diagnosis and patient
      management.

PMID- 9517564
TI  - Supporting cell proliferation in the olfactory epithelium decreases postnatally.
AB  - It is well known that progenitor cells in the basal layer of olfactory epithelium
      proliferate continuously throughout life; the offspring of these dividing cells
      produce replacements for receptor neurons. In the rat the number of proliferating
      basal cells/mm length of epithelium (proliferation density) decreases with
      postnatal age while the area of the olfactory sheet increases. The supporting
      cells, which act as the glia of the olfactory epithelium, also divide. We
      examined in detail some aspects of the dynamics of olfactory supporting cell
      proliferation to determine whether their rate of proliferation changes with age,
      and how it compares with the rate in basal progenitor cells. Using BrdU to label
      dividing cells, we determined the proliferation density of supporting cells and
      basal cells in 10 microm coronal sections from six different anterior-posterior
      regions in rats ranging in age from birth (P1) until P333. We observed a dramatic
      decrease in supporting cell proliferation density from P1 (80 cells/mm) to P11
      (32 cells/mm) to P21 (12 cells/mm); the density decreases continuously to P333
      (0.4 cells/mm). This reduction was even more dramatic than that in the basal cell
      population (Weiler and Farbman, 1997). Analysis of the data for correlation
      between basal and supporting cell proliferation revealed a weak correlation in
      neonates but no correlation in older animals. This suggests that the mechanisms
      that regulate proliferation of the two cell types are different. Our data also
      indicate that the proliferation of supporting cells is related only to growth in
      surface area of the epithelium. No turnover seems to occur in the supporting
      cells as it does in the olfactory neurons, where proliferation of basal cells is
      necessary for both growth and replacement.

PMID- 9517565
TI  - Specific pattern of nitric oxide synthase expression in glial cells after
      hippocampal injury.
AB  - In the central nervous system (CNS), nitric oxide (NO) is thought to be involved
      in a variety of functions including synaptic plasticity, long term potentiation,
      and neurotoxicity. The aim of the present study was to investigate the expression
      of nitric oxide synthase (NOS) in the mouse CNS, following surgical injury to the
      hippocampus. NOS expression was assessed by histochemical detection of
      nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-diaphorase)
      activity and immunohistochemistry of the inducible NOS (iNOS). Two days after
      injury to the CA1 hippocampal field, NADPH-diaphorase activity was detected in
      pyramidal and granular neurons and also in glial cells in the hippocampus, in
      contrast to the non-injured one where NADPH-diaphorase staining was observed only
      in a few interneurons. NADPH-diaphorase histochemistry combined with
      immunolabelling for GFAP and F4/80 demonstrated that these glial cells were
      astrocytes and microglia. This pattern of NOS expression is induced specifically
      after a hippocampal injury since lesion to the prefrontal or cerebellar cortex
      leads to NOS activity only in monocytes/macrophages like cells. Despite the large
      expression of NOS detected by NADPH-diaphorase histochemistry after lesioning the
      hippocampus, immunostaining for iNOS was confined to microglia. The fact that
      induction of high levels of NOS activity are detected in glial cells after a
      lesion to the hippocampus could be accounted for by the sensitivity of this
      structure to a high release of glutamate.

PMID- 9517566
TI  - Enhanced GFAP expression in astrocytes of transgenic mice expressing the human
      brain-specific trypsinogen IV.
AB  - We recently identified a cDNA encoding a human brain specific trypsinogen
      (trypsinogen IV). In order to test whether trypsinogen IV is involved in CNS
      diseases of, or injury response in, mammalian brain, a mouse model was developed
      in which the human trypsinogen IV was expressed specifically in neurons.
      Immunocytochemical analysis of the brains of transgenic mice revealed a striking
      enhancement of glial fibrillar acidic protein (GFAP) expression in astrocytes.
      This remarkable astrocytic reaction was detected in the brains of mice as young
      as 2 months and did not diminish in the older animals we tested. However, we did
      not find gross evidence for neurodegeneration, nor for reactive microglial cells.
      The long-term survival of these animals should provide a model with which to
      study the mechanism of nerve-astroglia interactions. In addition, the possible
      participation of trypsin IV in the metabolism of the Alzheimer precursor protein
      (APP) was investigated by immunostaining brains from transgenic mice with beta
      amyloid (betaA4) antibodies. Immunocytochemical staining of brains from one year
      old transgenic mice revealed an intense intracellular betaA4-like signal in
      neurons.

PMID- 9517567
TI  - Mouse resident microglia: isolation and characterization of immunoregulatory
      properties with naive CD4+ and CD8+ T-cells.
AB  - We describe a non-enzymatic procedure designed to isolate in high purity resident
      microglia from the brains of normal mice. This procedure allowed for the
      characterization of the cells without concern that their surface features had
      been enzymatically altered during tissue processing. A cell population was
      obtained and judged to consist primarily of microglia because essentially all the
      cells were Mac-1+, Mac-3+, F4/80+, CD44+, CD54+, and CD86+, and they expressed
      CD45 with a mean fluorescence intensity value of about one-half that of tissue
      macrophages. The cells also expressed marginal levels of MHC class I, CD14, CD40,
      and CD80, but lacked detectable MHC class II, CD4, CD8, CD45R, and CD102
      molecules. Molecular phenotyping revealed that the purified microglial population
      contained mRNA transcripts encoding the receptor for colony stimulating factor-1
      (CSF-1), the macrophage growth factor, and contained few, if any, transcripts for
      glial fibrillary acidic protein, an astrocyte-specific marker. Ex vivo, the
      microglia constitutively stimulated, in the mixed leukocyte reaction, the
      proliferation of naive allogeneic CD8+, but not CD4+ T-cells. However, they
      failed to present a protein antigen to naive antigen-specific CD4+ T-cells unless
      pretreated with interferon-gamma, a response that was inhibited by antibodies to
      CD86. Agar-cloning experiments confirmed that normal mouse brain contains a CSF-1
      responsive cell that gave rise to cells with identical immunophenotypic
      characteristics as freshly isolated resident microglia. Moreover, the microglial
      progenitor cell located in a density fraction that was different from that
      containing the mature resident microglia.

PMID- 9517568
TI  - ATP-induced arachidonic acid release in cultured astrocytes is mediated by Gi
      protein coupled P2Y1 and P2Y2 receptors.
AB  - ATP-induced arachidonic acid (AA) release was studied in [3H]AA-prelabeled
      cultured astrocytes. To characterize the P2 purinoceptor-mediated effect of ATP,
      the subtype-specific agonists 2-methylthio ATP (2-MeSATP) and UTP were compared.
      ATP, UTP, or 2-MeSATP induced a dose-dependent increase of [3H]AA release, with
      EC50 values of 22.7 microM, 29.4 microM, and 1.68 microM, respectively;
      alpha,beta-methyleneATP and adenosine had no effect. The order of potency was ATP
      = UTP > or = 2-MeSATP, indicating that ATP interacted with both P2Y1 and P2Y2
      receptors to mediate AA release in astrocytes. The effect of ATP, UTP, or 2
      MeSATP was markedly inhibited by pretreatment of cells with pertussis toxin. Ca2+
      ionophore-A23187 and PKC activator-TPA mimicked the effects of these three
      agonists to stimulate AA release. ATP, UTP, and 2-MeSATP induced a rapidly
      initial rise of [Ca2+]i and a sustained [Ca2+]i increase. The AA release was
      blocked in the external Ca2+ free in condition the sustained [Ca2+]i increase was
      abolished. Both A23187- and TPA-induced AA release were also blocked in this
      condition. Furthermore, inorganic Ca2+ channel blocker Co2+ inhibited ATP, UTP,
      or 2-MeSATP induced AA release as well. Long-term (24 h) treatment of cells with
      TPA resulted in an attenuation of three agonists, TPA or A23187 response.
      Similarly, ATP or TPA promoted AA release was inhibited by the mitogen-activated
      protein kinase (MAPK) cascade inhibitor PD 98059. ATP, TPA, or A23187 induced an
      increase in the activity and tyrosine phosphorylation of p42 MAPK, as well as a
      molecular weight shift, consistent with phosphorylation, of cytosolic
      phospholipase A2 (cPLA2). ATP- and TPA-stimulated activation of p42 MAPK activity
      and tyrosine phosphorylation were inhibited by long-term TPA treatment, while
      A23187-stimulated effects were completely blocked. Furthermore, tyrosine
      phosphorylation and activation of p42 MAPK and mobility shift of cPLA2 induced by
      A23187 were reversed in the absence of external Ca2+, suggesting the involvement
      of PKCalpha in MAPK activation and mobility shift of cPLA2. Taken together, ATP
      stimulated AA release was secondary to the activation of P2Y1 and P2Y2
      receptors/PLC pathway. Ca2+ and PKC interact to regulate this response. Elevation
      of intracellular Ca2+, the mechanism involving extracellular Ca2+ influx, might
      act partly through PKCalpha activation and in turn MAPK might be activated,
      leading to cPLA2 phosphorylation and AA release.

PMID- 9517569
TI  - Peroxide-scavenging deficit underlies oligodendrocyte susceptibility to oxidative
      stress.
AB  - Previous work showed that the susceptibility of oligodendroglial progenitors to
      oxidative stress is related to their low reduced-glutathione (GSH) and high iron
      contents. This suggests that these cells have a poor ability to scavenge
      peroxides. All peroxides are scavenged by glutathione peroxidase. Glutathione
      peroxidase activity requires GSH as an electron donor resulting in the formation
      of oxidized-glutathione. Cellular GSH content is dependent upon synthesis as well
      as reduction of oxidized-glutathione. The objectives of the present study were to
      compare several parameters important in the ability to scavenge peroxides between
      astrocytes and oligodendroglia. Three stages of oligodendroglial differentiation
      were examined: the proliferative oligodendrocyte progenitor, the proliferative
      oligodendroblast, and the post-mitotic oligodendrocyte. We demonstrate that
      oligodendroglia at all stages of differentiation have less than one-half the
      content of GSH compared to astrocytes. This low level of GSH is due in part to a
      lower rate of GSH synthesis in oligodendroglia compared to astrocytes and in part
      to their having only one-half of the glutathione reductase activity of
      astrocytes. Glutathione peroxidase activity of oligodendroglia is less than 15%
      of that found in astrocytes. The low GSH and concomitant low glutathione
      peroxidase activity would tend to maintain peroxides at levels that are
      dangerously high if iron is released from iron stores. Oligodendroglia have high
      iron stores, and thus these findings emphasize how vulnerable the
      oligodendroglial lineage is to perturbations that result in oxidative stress.

PMID- 9517570
TI  - Homotypic cell contact-dependent inhibition of astrocyte proliferation.
AB  - The normal adult vertebrate nervous system is a relative quiescent tissue in
      terms of cell proliferation. However, astrocytes in many regions of the central
      nervous system (CNS) retain the capacity to undergo cell division. To examine the
      mechanisms that regulate the proliferation of astrocytes in the CNS we have
      utilized an in vitro assay in which astrocyte density and cellular environment
      could be regulated. We demonstrate that type 1 astrocytes derived from the
      cerebral cortex of developing rats exhibit a profound density-dependent
      inhibition of proliferation. This inhibition of proliferation was cell type
      specific, but not restricted to type 1 astrocytes. NIH 3T3 cells but not smooth
      muscle cells inhibited astrocyte proliferation, while contact-inhibited
      astrocytes did not inhibit oligodendrocyte proliferation. Co-culture of type 1
      astrocytes with neurons from a variety of sources resulted in induction of a
      process-bearing astrocyte morphology and promoted glial cell proliferation. Thus,
      induction of a process-bearing astrocyte morphology does not lead to a cessation
      of proliferation. The inhibition of astrocyte proliferation did not appear to be
      mediated through the release or sequestration of soluble factors but rather could
      be induced by membrane-associated factors.

PMID- 9517572
TI  - NF-kappaB modulates lipopolysaccharide-induced microglial nerve growth factor
      expression.
AB  - Microglia/brain macrophages activated in response to injury, infection, or
      inflammation of the central nervous system (CNS) mediate both neurotoxic and
      neurotrophic activities. Although the cytotoxic effects of microglia have been
      analyzed in detail, little is known about the signaling pathways involved in
      microglial neurotrophin expression. Using purified rat microglial cell cultures,
      the effects of inflammatory agents such as lipopolysaccharide (LPS) on microglial
      nerve growth factor (NGF) expression were studied. Application of LPS (0.1-100
      ng/ml) induced a rapid (2-4 h), dose-dependent increase in NGF mRNA expression
      followed by enhanced release of NGF protein within 24 h. To determine whether the
      transcription factor NF-kappaB, known to be stimulated in activated microglia, is
      involved in inflammatory mediator-induced NGF expression, we used the NF-kappaB
      inhibitor pyrrolidine dithiocarbamate (PDTC). Addition of PDTC (100 microM) to
      microglia completely abolished LPS-induced NGF synthesis, suggesting a key role
      for NF-kappaB in microglial NGF expression by inflammatory mediators. In
      conclusion, NF-kappaB-controlled NGF expression by activated microglia appears to
      contribute to the cross-talk between the immune and nervous systems during
      inflammation in the CNS.

PMID- 9517573
TI  - Distribution of mitochondrial manganese superoxide dismutase among rat glial
      cells in culture.
AB  - Enzymatic antioxidant defense systems, like superoxide dismutase (SOD), may
      protect neuronal and glial cells from reactive oxygen species (ROS) damage.
      Beside the cytosolic constitutive CuZn SOD, mitochondrial manganese SOD (Mn SOD)
      represents a ROS inducible enzyme which should allow the adaptation of brain
      cells to variation in ROS concentrations resulting from their oxidative
      metabolism. Using immunocytochemistry, the distribution of Mn SOD among the
      various representatives of the rat brain glial population (astroglia and
      microglia in primary culture as well as oligodendroglia in secondary culture) has
      been examined. Among astroglial cells, only a population of flat polygonal-shaped
      astrocytes, highly immunostained for glial fibrillary acid protein (GFAP) express
      Mn SOD immunoreactivity. Microglial cells defined by their shape and OX-42
      immunoreactivity also express an intense Mn SOD signal. Exposure of the primary
      culture to reactive oxygen species generated by a xanthine/xanthine oxidase
      mixture (X/XO) accentuates the Mn SOD signal in astroglial and microglial cells.
      On the contrary, oligodendroglial cells grown in secondary culture in a serum
      free chemically defined or a serum-containing medium and well characterized by
      their 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) immunoreactivity
      never express any immunostaining for Mn SOD, even in response to an extracellular
      reactive oxygen species generating source like X/XO. Likewise, a population of
      A2B5-positive glial cells which may represent bipotential O-2A progenitor
      precursors does not express Mn SOD immunostaining. These results point out that
      in addition to the well known ability of microglial and astroglial cells to
      secrete ROS, they also express a high mitochondrial oxygen superoxide
      decomposition potential. On the contrary, the absence of any observable Mn SOD
      signal in precursors and in more differentiated oligodendroglial cells could be
      related to their great sensitivity to ROS damage and could therefore play an
      important role in the development of various dysmyelinating disorders.

PMID- 9517571
TI  - Impaired induction of blood-brain barrier properties in aortic endothelial cells
      by astrocytes from GFAP-deficient mice.
AB  - Cell culture models have been extensively used for studies of blood-brain barrier
      (BBB) function. However, most in vitro models fail to reproduce the peculiar
      physiological and morphological properties of in situ brain microvascular
      endothelial cells. A recently developed, tridimensional and dynamic model of the
      BBB has permitted studies of glial-endothelial interactions in hollow fibers
      exposed to intraluminal flow. We have taken advantage of this technique and have
      investigated the ability of glial fibrillary acidic protein (GFAP)-deficient
      (GFAP-/-) astrocytes to induce BBB properties in aortic endothelial cells (BAEC)
      cultured in vitro. BAEC exposed to flow were seeded intraluminally in hollow
      fibers and co-cultured with extraluminally seeded mouse astrocytes. Under these
      conditions, astrocytes have been shown to induce blood-brain barrier properties
      in non-brain endothelial cells. We followed induction of a BBB phenotype by
      measuring the transendothelial resistance, as well as endothelial permeability to
      potassium, theophylline, 8-sulphophenyl-theophylline (8-SPT), sucrose, and Evans
      blue. Wild-type mouse astrocytes induced BBB properties in aortic endothelial
      cells following 3-4 weeks of co-culturing. Thus, these endothelial cells
      restricted passage of K+ ions into the extracapillary space and selectively
      excluded hydrophilic molecules, such as 8-SPT and 14C-sucrose. GFAP-/- astrocytes
      failed to induce a significant restriction to the passage of potassium and
      hydrophilic drugs (sucrose, 8-SPT), failed to induce transendothelial resistance
      values comparable to control co-cultures, but were capable of inducing exclusion
      of Evans blue by endothelial cells. These results suggest that GFAP (and
      intermediate filaments) may play a role in the induction of BBB properties in non
      BBB endothelial cells.

PMID- 9517574
TI  - Absence of polyomavirus JC in glial brain tumors and glioma-derived cell lines.
AB  - The human neurotropic papovavirus JC, a close relative of simian virus 40, has
      been associated with the formation of brain tumors in humans because of its
      ability to induce such tumors in other primates under experimental conditions.
      Here we have analyzed 30 brain tumors classified as either oligodendroglioma or
      astrocytoma and 22 cell lines derived from human gliomas for the presence of JC
      viral sequences using polymerase chain reaction with two different sets of
      primers. None of the tumors or cell lines contained JC viral sequences.
      Similarly, we failed to detect expression of JC T antigen in any of 26 human
      glioma lines analyzed in this study. We conclude that JC virus is not a major
      cause of human brain tumors.

PMID- 9517575
TI  - Inhaled glucocorticoids and acute asthma: therapeutic breakthrough or nonspecific
      effect?

PMID- 9517576
TI  - The host immune response to tuberculosis.

PMID- 9517577
TI  - Investigative use of bronchoscopy in asthma.
AB  - The incorporation of bronchoscopy and bronchoscopic procedures into the
      investigation of asthma mechanisms, treatment, and in particular, the role of
      airway inflammation has contributed significantly to the enhanced understanding
      of this disease. Carefully drafted guidelines have allowed the gradual inclusion
      of subjects with more severe disease in studies utilizing bronchoscopic
      investigative tools. Many more questions remained unanswered, including the
      importance of persistence of airway inflammation in asymptomatic asthma, the
      specific antiinflammatory effects of new (and old) asthma therapies, the
      contribution of airway structural changes (subepithelial fibrosis) to
      nonreversible obstruction, the role of antiinflammatory versus proinflammatory
      cytokines in the pathogenesis of airway inflammation and the heterogeneity of
      disease expression in various groups of subjects. We are confident that current
      and future meticulously designed and executed research studies utilizing
      bronchoscopic techniques will significantly add to our knowledge of disease
      mechanisms and lead us to new and improved treatments for asthma.

PMID- 9517578
TI  - Inhaled flunisolide for acute severe asthma.
AB  - This randomized, double-blind trial was designed to determine the benefit of high
      and cumulative doses of flunisolide added to salbutamol in patients with acute
      asthma in the emergency room (ER). Ninety-four patients who presented to an ER
      for treatment of an acute exacerbation of asthma were assigned in a randomized,
      double-blind fashion to receive salbutamol and placebo (n = 47) or salbutamol
      combined with flunisolide (n = 47). Both drugs were administered successively
      through a metered-dose inhaler and spacer at 10-min intervals for 3 h (400 microg
      of salbutamol and 1 mg of flunisolide every 10 min). In both groups, FEV1 and
      peak expiratory flow rate (PEFR) improved significantly over baseline values (p <
      0.01). Results in the flunisolide group were significantly different from those
      in the placebo group at 90, 120, 150, and 180 min. Data analyzed separately in
      accord with the duration of the attack before presenting at the ER (< 24 or > or
      = 24 h) showed that the placebo > or = 24 h group produced a significantly lower
      FEV1 at 120, 150, and 180 min (p = 0.041) than did the remaining groups. Our data
      support the theory that high and cumulative doses of inhaled flunisolide
      administered by metered-dose inhaler with spacer and added to salbutamol are an
      effective therapy for patients with acute asthma and a prolonged duration of
      symptoms before ER presentation.

PMID- 9517579
TI  - Association between corticosteroid use and vertebral fractures in older men with
      chronic obstructive pulmonary disease.
AB  - Osteoporosis is a major complication of long-term corticosteroid administration,
      but the magnitude of the effect in patients with chronic obstructive pulmonary
      disease (COPD) is not well defined. In a cross-sectional study, we evaluated the
      association between steroid use and vertebral fractures in 312 men, 50 yr of age
      or older, with COPD. Subjects were evaluated according to their corticosteroid
      use: Never Steroid Users (NSU) (n = 117), Inhaled Steroid Users (ISU) (n = 70),
      and Systemic Steroid Users (SSU) (n = 125). The prevalence of one or more
      vertebral fractures was 48.7% in the NSU group, 57.1% in the ISU group, and 63.3%
      in the SSU group. Compared with NSU, SSU were two times as likely to have one or
      more vertebral fractures: age-adjusted odds ratio (OR) = 1.80; 95% CI, 1.08 to
      3.07. This relationship was primarily due to a strong association between
      continuous systemic steroid use and vertebral fractures: age-adjusted OR = 2.36;
      95% CI, 1.26 to 4.38. In addition, fractures in SSU were more likely to be
      multiple and more severe. A weaker relationship existed between inhaled steroid
      use and vertebral fractures: age-adjusted OR = 1.35; 95% CI, 0.77 to 2.56
      compared with NSU. These data indicate that vertebral fractures are common in
      older men with COPD; the likelihood of these fractures is greatest in those men
      using continuous systemic steroids.

PMID- 9517580
TI  - Improved clearability of cystic fibrosis sputum with dextran treatment in vitro.
AB  - Most patients with cystic fibrosis (CF) are infected by Pseudomonas aeruginosa.
      Dextran exhibits anti-adhesive effects in preventing attachment of P. aeruginosa
      to epithelial cells (1). The initial purpose of this study was to evaluate the
      potential of dextran to alter the rheology and ciliary transportability of CF
      sputum prior to initiation of a clinical trial in patients with CF. Sputum
      samples were collected from 25 patients with CF not receiving rhDNase therapy for
      use in in vitro testing. Aliquots of CF sputum were treated with 10% vol.
      Ringer's or the same volume of Dextran 4000 to give a final concentration of 0.4%
      (4 mg/ml) or 4% (40 mg/ml) dextran in the sputum. Dog mucus samples were
      collected from seven healthy, anesthetized dogs from the endotracheal tube cuff.
      Aliquots of dog mucus were subjected to the same concentrations of dextran as the
      CF sputum. All treated samples were incubated for 30 min at 37 degrees C, and
      their rheologic properties (viscoelasticity) were evaluated by magnetic
      microrheometry. For 17 of the sputum samples, frog palate mucociliary
      transportability was determined from sputum movement on the ciliated, mucus
      depleted frog palate, relative to native frog mucus control. Spinnability
      (cohesiveness) was evaluated by the filancemeter technique for eight sputum
      samples. Overall, whether for CF sputum or healthy dog mucus, Dextran 4000
      treatment significantly reduced viscoelasticity and increased predicted
      mucociliary and cough clearability. Direct measurements of sputum mucociliary
      clearability on frog palate increased significantly with 0.4% dextran and 4%
      dextran compared with saline control. Sputum spinnability (cohesiveness)
      decreased significantly with both dextran concentrations, too. The effects on
      viscoelasticity and spinnability were greater at 4% than at 0.4%. There was a
      significant positive correlation between spinnability and viscoelasticity, and
      negative relationships between spinnability and both forms of clearability as
      predicted from viscoelastic measurements. This study suggests that treatment with
      Dextran 4000 can reduce the crosslink density and cohesiveness of CF and improve
      mucociliary and cough clearability. Dextran 4000 is an inexpensive and nontoxic
      agent that may be of benefit in patients with CF lung disease and perhaps in
      other respiratory disease where mucus retention is an important feature.

PMID- 9517581
TI  - Lung volume reduction surgery and airflow limitation.
AB  - Interest has recently been renewed in lung volume reduction surgery (LVRS) for
      end-stage emphysema. However, numerous questions about its role in the treatment
      of emphysema remain, including the clinical characteristics of optimal candidates
      and its mechanism of improvement in pulmonary function. In this report, we
      develop a mathematical analysis and graphic depiction of the mechanism of
      improvement in expiratory airflow and vital capacity. This analysis is based on
      consideration of the interaction between lung function and respiratory muscle
      function. We also reexamine previously published pulmonary mechanics in patients
      with alpha1-antitrypsin deficiency, chronic obstructive pulmonary disease, and
      asthma. We find a major determinant of airflow limitation common to these
      diseases is the ratio of residual volume to total lung capacity (RV/TLC).
      Moreover, RV/TLC is found to be the single most important determinant of the
      improvement in pulmonary function after LVRS. Regardless of the specific
      underlying lung disease, the impairment of airflow is due primarily to mismatch
      between the sizes of the lung and the chest wall, and the effects of LVRS are
      almost exclusively due to improvement of that match. This analysis can be used to
      develop testable hypotheses to guide patient selection for this procedure.

PMID- 9517582
TI  - The chemotactic activity of sputum from patients with bronchiectasis.
AB  - Persistent polymorphonuclear neutrophil (PMN) recruitment to airway is thought to
      be an important component of continuing inflammation and progression of chronic
      destructive lung diseases. Although chemoattractants are required for the PMN to
      migrate, the nature of the chemoattractants in the airways has not yet been
      clarified. We therefore investigated the contribution of interleukin-8 (IL-8) and
      leukotriene-B4 (LTB4) to the chemotactic activity of lung secretions by
      inhibiting their activity using a monoclonal antibody to IL-8 and an LTB4
      receptor antagonist (LY293111 sodium). Fifty-nine sputum samples obtained from 19
      patients with bronchiectasis were studied. In preliminary studies the chemotactic
      responses to IL-8 and LTB4 were found to be additive, and we were able to remove
      their contribution independently with the appropriate antibody and antagonist.
      The chemotactic activity of the secretions was related to the macroscopic
      appearance (mucoid, mucopurulent, and purulent), and this appeared to be related
      to an increase in IL-8 contribution. Chemotactic activity was reduced by
      antibiotic therapy and again that seemed to relate to a reduction in the IL-8
      contribution. The contributions of LTB4 were similar among the three types of
      sputum in varying clinical states. These data suggest that LTB4 and IL-8 are
      important chemotactic factors in lung secretions from such patients, although IL
      8 appears to play a more important role during acute exacerbations. These results
      may be useful in determining therapeutic strategies for chronic destructive lung
      diseases in the future.

PMID- 9517583
TI  - Local immune responses correlate with presentation and outcome in tuberculosis.
AB  - Local cellular immune responses may affect presentation and outcome in
      tuberculosis (TB). To investigate this hypothesis, we performed bronchoalveolar
      lavage (BAL) on 30 patients with untreated pulmonary tuberculosis and assessed
      the type of cellular inflammatory response and cytokine production. We then
      correlated BAL findings and cytokine production with clinical findings. We also
      performed BAL on a subset of patients to examine changes in cytokine production
      by BAL cells over time. We found that at presentation patients with less
      clinically and radiographically advanced TB (smear-negative, noncavitary disease)
      had a local immune response characterized by a predominance of lymphocytes.
      Furthermore, BAL cells from these patients secreted interferon (IFNgamma), and
      not Interleukin-4, suggesting a Th 1-type lymphocytic response. In patients with
      smear-positive and/or cavitary disease, macrophages or polymorphonuclear
      leukocytes were the predominant BAL cell type, but with treatment and clinical
      improvement these patients went on to recruit IFNgamma producing cells to the
      lung. We conclude that the type of cellular immune response that occurs locally
      in the lung may affect presentation and outcome in pulmonary TB, and an
      understanding of the development of this response may lead to insights into
      pathogenesis and novel therapies for TB.

PMID- 9517584
TI  - Delayed diaphragm injury and diaphragm force production.
AB  - The present study was designed to examine the effect of delayed diaphragm injury
      produced by inspiratory resistive loading (IRL) on diaphragm force production. On
      Day 1, three groups of anesthetized and intubated NZW rabbits (n = 7 in each
      group) were subjected to moderate IRL (Pao approximately 30 cm H2O), high IRL
      (Pao approximately 45 cm H2O), or no load for 1.5 h. On Day 3, the baseline
      twitch transdiaphragmatic pressure (Pdi) and Pdi at 10 to 80 Hz were measured
      during bilateral phrenic stimulation and these measurements were repeated after
      another IRL (high level) in all three groups. Diaphragm injury was assessed by
      the point-counting technique. Marked diaphragm injury was observed in the high
      IRL group (p < 0.01), but no significant diaphragm injury was observed in the
      moderate-IRL or control groups. The baseline twitch Pdi was maintained in both
      IRL groups, whereas the baseline Pdi-frequency values in the high-IRL group were
      significantly reduced at most frequencies (p < 0.05). The decreases in twitch and
      Pdi at different frequencies were more pronounced after the IRL on Day 3 in the
      high-IRL group compared with controls. Moderate IRL did not decrease diaphragm
      force either before or after the high IRL on Day 3. We conclude that the
      diaphragm injury induced by high IRL has a significant impact on diaphragm force
      production and the attendant force loss produced by IRL is dependent on the
      intensity of inspiratory loading.

PMID- 9517585
TI  - Exposure to commonly prescribed drugs and the etiology of cryptogenic fibrosing
      alveolitis: a case-control study.
AB  - Cryptogenic fibrosing alveolitis is an interstitial lung disease of unknown
      etiology. Since pulmonary fibrosis is a recognized, if rare, complication of
      certain drug exposures, including antidepressants, betablockers, antibiotics,
      anticonvulsants, and nonsteroidal antiinflammatory drugs (NSAIDs), we tested the
      hypothesis that exposure to these drugs might contribute to the etiology of
      cryptogenic fibrosing alveolitis. Lifetime drug exposure data were collected from
      general practitioner records for 141 cases of cryptogenic fibrosing alveolitis
      and 246 age-, sex-, and community-matched control subjects from the Trent region
      of England. Additional data on lifetime smoking habits were obtained by postal
      questionnaire. The odds of disease in relation to ever exposure to
      antidepressants, betablockers, antibiotics, anticonvulsants, and NSAIDs were
      calculated by conditional logistic regression. For drug groups significantly
      associated with cryptogenic fibrosing alveolitis, subset analyses were performed
      to investigate the effects of individual drugs. Cryptogenic fibrosing alveolitis
      was associated with exposure to antidepressants (odds ratio [OR] 1.79 [95% CI
      1.09-2.95], p = 0.022) and specifically to imipramine (OR 4.79 [1.50-15.3], p =
      0.01), dothiepin (OR 2.37 [0.99-5.69], p = 0.05), and mianserin (OR 3.27 [1.11
      9.61], p = 0.03). The magnitude of the overall effect of antidepressants was not
      changed by excluding all drug exposures within the 5 yr preceding the diagnosis
      of cryptogenic fibrosing alveolitis (OR 1.62 [0.94-2.77], p = 0.081), nor were
      the strong individual effects of imipramine (OR 5.72 [1.54-21.2], p = 0.009) and
      dothiepin (OR 5.58 [1.12-27.8], p = 0.036). These estimates were not appreciably
      affected by controlling for smoking history. The attributable risk for
      antidepressant exposure was in the region of 9-14%. No significant association
      was noted between cryptogenic fibrosing alveolitis and the four other drug groups
      in the primary hypothesis. The results of this study suggest that some
      antidepressant drugs can cause cryptogenic fibrosing alveolitis.

PMID- 9517586
TI  - Association of cigarette smoking and asbestos exposure with location and
      histology of lung cancer.
AB  - Prior studies have suggested that lung cancers that arise in association with
      cigarette smoking favor an upper-lobe location while those associated with
      asbestos exposure favor a lower-lobe location. An excess of adenocarcinomas has
      also been reported among cases not exposed to cigarette smoke as well as among
      those exposed to asbestos. However, these studies typically have not adjusted
      adequately for potential confounders such as the patient's age, sex, race, or
      family history of cancer. To better examine the effects of cigarette smoking and
      asbestos exposure on location and histology of lung cancer, we analyzed data from
      a large case-control study that included 456 patients with stage I or II lung
      cancer. Patients with upper-lobe tumors tended to have had more exposure to
      tobacco as assessed by pack-years smoked (54.7 versus 46.2, p = 0.07) and less
      time since quitting smoking (3.0 versus 5.5 yr, p = 0.05). In contrast to some
      prior reports, asbestos exposure was also associated with an upper-lobe location
      of tumor. Among those with upper-lobe tumors, 14.6% had a history of significant
      asbestos exposure compared with 5.4% of those with lower-lobe tumors (p < 0.01).
      The relationship between asbestos exposure and upper-lobe location of tumor was
      also statistically significant whether stratified by smoking or analyzed by
      multivariable logistic regression modeling. Adenocarcinomas were more likely
      among those with less exposure to cigarette smoke based on fewer pack-years
      smoked (41.5 versus 61.8, p = 0.0001) and more time since quitting smoking (5.0
      versus 3.0 yr, p = 0.02). The proportion of patients with significant exposure to
      asbestos was lower among those with adenocarcinomas but was not statistically
      significant (9.5 versus 15.3%, p = 0.09). In multivariable logistic regression
      analysis, longer time since smoking exposure remained a significant predictor of
      adenocarcinomas (p < 0.02), but history of asbestos exposure did not predict
      tumor histology. Thus, in patients with lung cancer, both cigarette smoking and
      asbestos exposure histories favor an upper-lobe location of tumor. Longer time
      since smoking exposure favors adenocarcinomas, but the history of asbestos
      exposure does not appear to influence the tumor histology.

PMID- 9517587
TI  - Neutrophil adhesion molecule surface expression and responsiveness in cystic
      fibrosis.
AB  - The neutrophil-dominated inflammation of the lung in cystic fibrosis (CF) has
      traditionally been seen as a physiological response to continuous opportunistic
      infection. Recent studies suggest, however, that regulation of the inflammatory
      response itself may be altered in CF. Neutrophil migration from the bloodstream
      involves alterations in surface expression of the adhesion molecules L-selectin
      and Mac-1 (CD11b/CD18). The aim of this study was to assess neutrophil adhesion
      molecule expression and responsiveness in CF. Neutrophils from chronic (n = 16)
      and acutely infected (n = 13) CF patients and 15 normal control subjects were
      directly assessed by Fluorescence-activated cell sorter (FACS) analysis for
      surface expression of L-selectin and CD11b before and after stimulation with
      interleukin 8 (IL-8) or f-Met-Leu-Phe (fMLP). Neutrophils from stable (n = 5) and
      acutely infected (n = 5) non-CF bronchiectasis patients were also assessed.
      Surface upregulation of CD11b was similar in all groups. Basal levels of L
      selectin were also comparable among all groups, however, when stimulated,
      neutrophils from both stable and acutely infected CF patients shed significantly
      less L-selectin than those from control subjects (p < 0.05 and p < 0.01,
      respectively). This decreased responsiveness was not observed in either stable or
      acutely infected non-CF bronchiectasis patients. These results add to the
      accumulating evidence suggestive of a defective inflammatory response in CF.

PMID- 9517588
TI  - Serum level of interleukin 8 is elevated in idiopathic pulmonary fibrosis and
      indicates disease activity.
AB  - It has been shown that interleukin 8 (IL-8) is increased in bronchoalveolar
      lavage fluid (BALF) of patients with idiopathic pulmonary fibrosis (IPF) and
      there is increasing evidence that it is involved in the pathogenesis of this
      disease. To date, no data are available as to whether IL-8 is elevated in sera of
      IPF patients. We obtained sera from 42 patients with IPF and 20 healthy controls
      at time of BAL. From 20 of 42 patients with IPF and 12 of 20 controls BALF was
      available, enabling us to measure IL-8 in serum and BALF of the same time point.
      IL-8 was significantly elevated in serum (54.7 +/- 7.5 pg/ml, p < 0.0001) and
      BALF (715.7 +/- 112.4 pg/ml, p < 0.0001) of patients with IPF compared with
      controls (IL-8 in serum, 5.2 +/- 0.8 pg/ml; IL-8 in BALF, 67.3 +/- 9.7 pg/ml). We
      observed a significant positive correlation between IL-8 levels in BALF and
      percentage of BALF neutrophils (p < 0.001) and between serum IL-8 and BALF IL-8
      levels (p < 0.005) in patients with IPF. Consequently, the serum IL-8 level
      correlated positively with the percentage of BAL neutrophils (p < 0.01),
      indicating that it may reflect the degree of neutrophilic alveolitis in IPF.
      Furthermore, the serum IL-8 level showed a negative correlation with important
      indicators of impairment of lung function (DL(CO), TLC, VC) and PaO2. In
      conclusion, we were able to demonstrate that the degree of neutrophilic
      alveolitis in IPF is reflected by increased serum levels of IL-8 and we suggest
      that the serological assessment of IL-8 may provide a useful parameter for
      clinicians in monitoring patients with IPF.

PMID- 9517589
TI  - Expired nitric oxide after bronchoprovocation and repeated spirometry in patients
      with asthma.
AB  - Compared with normal individuals, subjects with asthma have elevated levels of
      expired nitric oxide (NO). These levels are hypothesized to reflect the degree of
      airway inflammation. Expired NO levels rise during the late phase of allergen
      challenge and decrease in asthmatics after steroid treatment. Isocapnic cold air
      hyperventilation (ISH) is believed to cause airway narrowing through
      noninflammatory mechanisms. We measured mixed expired NO in 10 individuals with
      atopic asthma who underwent both ISH challenge and allergen challenge, and
      compared these measurements with the change in expired NO that occurred after
      serial spirometry alone. We found that ambient NO levels affected mixed expired
      NO. Controlling for inspired NO, we found that repeated spirometry alone produced
      a significant fall in mixed expired NO (p < 0.01) that was maximal after 30 min
      (36.6 +/- 8.5% fall). After allergen and ISH challenges, expired NO was elevated
      relative to levels after repeated spirometry (p < 0.01 and p = 0.065,
      respectively). In addition, we found that prechallenge expired NO levels were
      significantly correlated with the magnitude of the late fall in FEV1 following
      allergen challenge (r = 0.80, p < 0.01). These data demonstrate that repeated
      spirometry results in reduced mixed expired NO and suggest that both ISH and
      allergen-induced bronchoconstriction share pathobiologic mechanisms that produce
      increases in mixed expired NO.

PMID- 9517590
TI  - Elevated circulating E-selectin, intercellular adhesion molecule 1, and von
      Willebrand factor in patients with severe infection.
AB  - To investigate interactions between the endothelium and leukocytes in patients
      with sepsis, we measured soluble adhesion molecules (sE-selectin and sICAM-1),
      von Willebrand factor antigen (vWf:Ag), myeloperoxidase (MPO), and lactoferrin
      (Lacto-f) as plasma markers of endothelial and neutrophil activation. We tested
      whether the five proteins were predictors of clinical severity, which was
      evaluated by simplified acute physiological score (SAPS), number of organ
      failures (MOF), acute lung injury (ALI), and subsequent final outcome. Levels of
      the five plasma markers were higher in patients with severe infection (n = 25)
      than in patients without sepsis (n = 7) and healthy volunteers (n = 9). In the
      study population, levels of sE-selectin, sICAM-1, and vWf:Ag were higher for
      nonsurvivors as well as for patients with septic shock or with bacteremia, and
      they were correlated with SAPS and MOF. Survival outcome was predicted with high
      sensitivity and specificity by initial plasma levels of sICAM-1 and vWf:Ag. The
      initial sICAM-1 level appeared to be an independent prognostic variable, based on
      a logistic regression analysis. Unlike sE-selectin, sICAM-1 remained at high
      levels indefinitely in nonsurvivors. We conclude that, unlike neutrophil
      activation markers, levels of endothelium-derived soluble adhesion molecules and
      vWf:Ag in severe sepsis syndrome are correlated with the severity of illness and
      may be considered as predictors of survival outcome.

PMID- 9517591
TI  - Comparison of discriminative properties among disease-specific questionnaires for
      measuring health-related quality of life in patients with chronic obstructive
      pulmonary disease.
AB  - Three disease-specific, health-related quality of life (HRQL) questionnaires have
      been introduced to assess patients with chronic obstructive pulmonary disease
      (COPD): the St. George's Respiratory Questionnaire (SGRQ), the Breathing Problems
      Questionnaire (BPQ), and the Chronic Respiratory Disease Questionnaire (CRQ). The
      purpose of the present study was to make comparisons between the SGRQ, the BPQ,
      and the CRQ in their discriminative properties, and to clarify the
      characteristics of each questionnaire. One hundred forty-three patients with mild
      to severe COPD completed pulmonary function tests, progressive cycle ergometer
      testing for exercise capacity, assessment of dyspnea, anxiety, and depression,
      and assessment of HRQL. The frequency distributions of the questionnaire scores
      showed that the SGRQ and the CRQ were normally distributed and that the BPQ was
      skewed toward low scores. Relationships between all dimensions of the three
      questionnaires were significant (correlation coefficients [Rs] = 0.74 to 0.86).
      The three questionnaires had significant but weak correlations (Rs = -0.24 to 
      0.36) with some physiologic variables (VC, FEV1, and DL(CO)/VA) and mild to
      moderate correlations with exercise capacity and assessment of dyspnea, anxiety,
      and depression. Stepwise multiple regression analyses revealed that the Baseline
      Dyspnea Index (BDI) score, anxiety by the Hospital Anxiety Depression Scale
      (HAD), and maximal oxygen uptake (VO2max) accounted for 61% of the variance in
      the SGRQ and that the BDI and anxiety of the HAD accounted for 53 and 49% of the
      variance in the BPQ and the CRQ, respectively. Dyspnea and psychologic status
      impacted the HRQL in patients with COPD. Although no substantial differences
      between the SGRQ, the BPQ, and the CRQ were evident in the correlations with
      physiologic parameters and the influential factors, the BPQ was found to be less
      discriminatory than the SGRQ and the CRQ in evaluating HRQL cross-sectionally.

PMID- 9517592
TI  - Air contamination with nitric oxide: effect on exhaled nitric oxide response.
AB  - This study examines the response of exhaled nitric oxide (NO) concentration
      (ECNO) and quantity of exhaled NO over time (EVNO) in 10 healthy subjects
      breathing into five polyethylene bags, one in which synthetic air was free of NO
      and four in which NO was diluted to concentrations of 20 +/- 0.6, 49 +/- 0.8, 98
      +/- 2, and 148 +/- 2 ppb, respectively. Each subject was connected to each bag
      for 10 min at random. Minute ventilation and ECNO were measured continuously, and
      EVNO was calculated continuously. ECNO and EVNO values were significantly higher
      for an inhaled NO concentration of 20 ppb than for NO-free air. Above 20 ppb,
      ECNO and EVNO increased linearly with inhaled NO concentration. It is reasonable
      to assume that a share of the quantity of inspired NO over time (InspVNO) because
      of air contamination by pollution is rejected by the ventilatory pathway. Insofar
      as InspVNO does not affect endogenous production or the metabolic fate of NO in
      the airway, this share may be estimated as being approximately one third of
      InspVNO, the remainder being taken by the endogenous pathway. Thus, air
      contamination by the NO resulting from pollution greatly increases the NO
      response in exhaled air.

PMID- 9517593
TI  - Oxygen supply dependence of urea production in the isolated perfused rat liver.
AB  - To determine whether hepatic urea production is limited at low hepatic O2
      delivery (DO2) by O2 itself or by the availability of substrate for urea
      synthesis, we isolated livers from normal rats and perfused them with Krebs
      Henseleit bicarbonate (KHB) buffer, KHB + 5 mM NH4Cl, or KHB + 5 mM glutamine
      (Gln) as an NH3 donor. The pump flow was lowered in stages, and we determined at
      each flow rate inflow and outflow O2 content and urea levels in the outflow
      perfusate. Urea production in Gln-perfused livers remained constant at high DO2
      and declined in direct proportion to DO2 below a critical oxygen delivery
      (DO2crit, the point below which the hepatic O2 consumption [VO2] becomes limited
      by the hepatic DO2). The DO2crit calculated from the urea release-DO2
      relationship (147 +/- 32 microl/min/dry g) was similar to the DO2crit calculated
      from the VO2-DO2 relationship (158 +/- 26 microl/min/dry g). When Gln
      concentration and flow rate were maintained constant while decreasing PO2 in the
      inflow perfusate (as well as hepatic DO2), urea production declined below the
      DO2crit. Furthermore, when Gln concentration in the perfusate was gradually
      reduced while keeping hepatic DO2 constant, urea production decreased
      proportionally with Gln concentrations in the perfusate. Consequently, urea
      production is dependent on Gln and O2 availability and becomes limited at the
      same DO2crit determined by the VO2-DO2 relationship.

PMID- 9517594
TI  - Albuterol does not antagonize the inhibitory effect of dexamethasone on monocyte
      cytokine release.
AB  - Beta2-adrenoceptor agonists given by the inhaled route are the most effective
      bronchodilators known, yet high doses of these drugs may be associated with an
      increase in asthma mortality and morbidity. One theory for this paradox is that
      chronic use of beta2-adrenoceptor agonists compromises the anti-inflammatory
      action of glucocorticosteroids. This hypothesis derives from the ability of
      albuterol and fenoterol to inhibit the interaction of the glucocorticosteroid
      receptor (GR) with proinflammatory transcriptional activators acting on the
      promoter region of certain target genes that encode cytokines such as tumor
      necrosis factor-alpha (TNF alpha) and granulocyte/macrophage colony-stimulating
      factor (GM-CSF). However, the functional relevance of these results has not been
      formally investigated. We have tested the hypothesis that albuterol reduces the
      ability of dexamethasone to inhibit the generation of TNF alpha and GM-CSF from
      lipopolysaccharide (LPS)-stimulated human monocytes. Pretreatment of human
      monocytes with albuterol (1 and 100 microM) for 5 and for 180 min inhibited
      maximally TNF alpha generation by approximately 25%. However, regardless of the
      concentration of albuterol, or the time of preincubation, the inhibitory effect
      of dexamethasone was not significantly affected with respect to the EC50 or the
      maximal effect produced. Qualitatively identical data were obtained when GM-CSF
      release was used as an index of monocyte activation. We conclude that high
      concentrations of albuterol do not compromise the ability of dexamethasone to
      suppress the generation of TNF alpha and GM-CSF from LPS-stimulated human
      monocytes.

PMID- 9517595
TI  - Endogenous surfactant turnover in preterm infants measured with stable isotopes.
AB  - We studied surfactant synthesis and turnover in vivo in preterm infants using the
      stable isotope [U-13C]glucose, as a precursor for the synthesis of palmitic acid
      in surfactant phosphatidylcholine (PC). Six preterm infants (birth weight, 916 +/
      244 g; gestational age, 27.7 +/- 1.7 wk) received a 24-h [U-13C]glucose infusion
      on the first day of life. The 13C-enrichment of palmitic acid in surfactant PC,
      obtained from tracheal aspirates, was measured by gas chromatography-combustion
      interface-isotope ratio mass spectrometry. We observed a significant
      incorporation of carbon-13 from glucose into surfactant PC palmitate. PC
      palmitate became enriched after 19.4 +/- 2.3 (16.5 to 22.3) h and reached maximum
      enrichment at 70 +/- 18 (48 to 96) h after the start of the label infusion. The
      fractional synthesis rate (FSR) of surfactant PC palmitate from glucose was 2.7
      +/- 1.3%/d. We calculated the absolute production rate of surfactant PC to be 4.2
      mg/kg/d, and the half-life to be 113 +/- 25 (87 to 144) h. Data on endogenous
      surfactant production and turnover were obtained for the first time in human
      infants with the use of stable isotopes. This novel and safe method could be
      applied to address many important issues concerning surfactant metabolism in
      preterm infants, children, and adults.

PMID- 9517596
TI  - Hypercapnia enhances the development of coughing during continuous infusion of
      water into the pharynx.
AB  - We investigated the effects of increasing CO2 ventilatory drive on the
      coordination of respiration and reflex swallowing elicited by continuous infusion
      of distilled water into the pharynx (2.5 ml/min) in 11 normal subjects.
      Ventilation was monitored using a pneumotachograph and swallowing was recorded by
      submental electromyogram. The CO2 ventilatory drive was increased by addition of
      external dead space, while ventilation, the frequency of swallows, and the timing
      of swallows in relation to the phases of the respiratory cycle were measured at
      steady-state conditions. We found that the CO2 ventilatory response is not
      influenced by continuous reflex swallowing but that hypercapnia influences the
      timing and frequency of these swallows. Signs of aspiration were never observed
      during continuous infusion of water at eucapnia, but seven of 11 subjects showed
      laryngeal irritation and/or pending aspiration during hypercapnia, and the
      incidence of laryngeal irritation was higher the greater the PCO2. Detailed
      analysis of laryngeal irritations consisting of single coughs in seven subjects
      revealed that the majority of laryngeal irritations occurred when swallows
      coincided with expiratory-inspiratory transition or when swallows coincided with
      inspiration, whereas laryngeal irritation after an expiratory swallow was never
      observed. These results suggest that the automatic respiratory control system is
      not influenced by continuous swallowing but that the coordination of swallowing
      and respiration may be compromised during hypercapnia.

PMID- 9517597
TI  - CD8+ T-lymphocytes in peripheral airways of smokers with chronic obstructive
      pulmonary disease.
AB  - To investigate whether the inflammatory process in peripheral airways is
      different in smokers who develop symptoms of chronic bronchitis and chronic
      airflow limitation and in asymptomatic smokers who do not develop chronic airflow
      limitation, we examined surgical specimens obtained from 16 smokers undergoing
      lung resection for localized pulmonary lesions. Nine had symptoms of chronic
      bronchitis and chronic airflow limitation and seven were asymptomatic with normal
      lung function. In peripheral airways, immunohistochemical methods were performed
      to identify neutrophils, macrophages, CD4+ and CD8+ T-lymphocytes infiltrating
      the airway wall, and morphometric methods were used to measure the internal
      perimeter, the airway wall area, and the smooth muscle area. The number of CD8+ T
      lymphocytes and the smooth muscle area were increased in smokers with symptoms of
      chronic bronchitis and chronic airflow limitation as compared with asymptomatic
      smokers with normal lung function, while the number of neutrophils, macrophages,
      and CD4+ T-lymphocytes were similar in the two groups of subjects examined. We
      concluded that smokers who develop symptoms of chronic bronchitis and chronic
      airflow limitation have an increased number of CD8+ T-lymphocytes and an
      increased smooth muscle area in the peripheral airways as compared with
      asymptomatic smokers with normal lung function, supporting the important role of
      CD8+ T-lymphocytes and airway remodeling in the pathogenesis of chronic
      obstructive pulmonary disease.

PMID- 9517598
TI  - Safety and efficacy of fluticasone and beclomethasone in moderate to severe
      asthma. Belgian Multicenter Study Group.
AB  - There are still some concerns about the safety of high doses of inhaled
      glucocorticosteroids (ICS). We compared the safety and efficacy of fluticasone
      propionate (FP) and beclomethasone dipropionate (BDP) in 306 patients with
      moderate to severe asthma in a double-blind, multicenter, cross-over study of 12
      mo duration. During the 1-mo run-in period, bronchodilators were replaced by
      salmeterol 50 microg twice daily, increasing morning peak expiratory flow rate
      (PEFR) by 28 L/min (p < 0.001) and FEV1 by 6.2% predicted (p < 0.001). At
      randomization the current ICS was replaced by 500 microg BDP or 250 microg FP in
      accordance with previously taken 500 microg BDP or 400 microg budesonide (BUD).
      No significant differences between the two treatments regarding morning plasma
      cortisol, urinary excretion of calcium and hydroxyproline, FEV1, and PEFR were
      observed at any time point during the study. Osteocalcin and bone mineral density
      (BMD) were improved over baseline in the FP group, resulting in higher serum
      osteocalcin levels (mean difference 0.28 ng/ml; p < 0.001) and higher BMD in the
      spine (1.0%; p = 0.05), femoral neck (1.6; p < 0.01), and Ward's triangle (3.6%;
      p = 0.01) as compared with BDP. We conclude that chronic treatment with FP, at
      half the dose of BDP, results in a similar antiasthma effect but a more favorable
      safety profile with respect to bone metabolism and mineral density.

PMID- 9517599
TI  - Low load inspiratory muscle training increases diaphragmatic fiber dimensions in
      rats.
AB  - The effects of 8 wk of inspiratory resistive loading (30 min/d, 3 x/wk) on
      diaphragm mass, contractile properties, fatigue, and fiber dimensions were
      studied in 10 male Wistar rats. They were conditioned to breathe through a Hans
      Rudolph device. Half of them had to overcome a moderate inspiratory resistance
      (MR; n = 5), whereas the others only had to overcome the small resistance (SR; n
      = 5) of the inspiratory valve of the device. Results were compared with control
      rats (C; n = 5) moving and breathing freely. At the end of training, animals
      submitted to MR and SR generated mean inspiratory pressures of -2.5 +/- 1.1 and 
      0.2 +/- 0.05 cm H2O, respectively. TI/Ttot was 0.60 +/- 0.06 and 0.57 +/- 0.05,
      respectively. Body and diaphragm weight were unaffected by loading. Little or no
      change in in vitro diaphragmatic twitch kinetics, force generation, and
      fatigability was found between the three groups. Nevertheless, cross-sectional
      area of all fiber types increased in the two loaded groups compared with control
      animals. This increase reached statistical significance for type I fibers in the
      MR group (846 +/- 74 microm2) compared with the C and SR groups (589 +/- 32 and
      683 +/- 96 microm2, respectively, p < 0.05). For IIa fibers both training groups
      were significantly different from the control group (SR: 768 +/- 99 and MR: 790
      +/- 108 versus C: 592 +/- 37 microm2, p < 0.05). A hypertrophy of type IIx/b
      fibers was seen in MR compared with control animals (C: 1,555 +/- 136, SR: 1,845
      +/- 338, MR: 2,053 +/- 326 microm2, p < 0.05). No differences were present in
      fiber type proportions between the three groups. We conclude that in our training
      setup, 8 wk of intermittent long-term inspiratory loading stressed the diaphragm
      already with a small resistance resulting in hypertrophy of predominantly type
      IIa fibers. A higher resistance resulted in hypertrophy of all fiber types.

PMID- 9517601
TI  - A comparative study of elastic properties of rat and guinea pig parenchymal
      strips.
AB  - Constricted guinea pig (GP) airways are much less sensitive to changes in
      transpulmonary pressure (Ptp) than are those of the rat. The object of this study
      was to investigate whether differences in the mechanical behavior of the lung
      parenchyma could explain differences between the two species in the
      interdependence of the airway and parenchyma. Subpleural lung strips from guinea
      pigs and rats were excised and suspended in an organ bath. One end of each strip
      was attached to a force transducer and the other to a servo-controlled lever arm
      that effected length (L) changes in the strip. Sinusoidal oscillations at varying
      frequencies and amplitudes were applied at different resting tensions.
      Measurements of L and resting tension (T) were recorded during baseline
      conditions and after acetylcholine (ACh) challenge. Elastance (E) and resistance
      (R) were calculated by fitting changes in T and L to the equation of motion.
      During sinusoidal oscillations, E and R in the two species were different in both
      the unconstricted and constricted states. The effect of T on E was significantly
      different in rats and GPs; E was less dependent on T in GPs. Insofar as E is a
      measure of the load against which airway smooth muscle (ASM) contracts, this
      difference may represent a potential mechanism to explain why constricted GP
      airways are less sensitive to changes in Ptp.

PMID- 9517600
TI  - Genetic and environmental risk factors for asthma: a cotwin-control study.
AB  - In complex diseases of genetic etiology such as asthma and atopy, it is difficult
      to differentiate causes of disease from consequences, and quantitate the
      importance of such causative factors. We examined possible risk factors for the
      development of wheezing and bronchial hyperresponsiveness in a cotwin-control
      study nested within a larger community-based twin-family study. In 62 monozygotic
      (MZ) twin pairs discordant for a history of wheezing, skin prick test to house
      dust extract was the most important discriminator, followed by sensitization to
      cat and cockroach allergens. In contrast, 62 dizygotic (DZ) discordant twin pairs
      differed additionally in sensitization to grass pollens and fungi. Markers such
      as serum haptoglobin, serum magnesium, and alpha-1-antitrypsin levels did not
      differ significantly between discordant twins. This MZ/DZ difference suggests
      that pollen allergy in asthmatics is more an epiphenomenon due to a genetic
      correlation between asthma and the allergic diathesis, whereas indoor allergens
      are likely to be direct environmental causes of asthma.

PMID- 9517602
TI  - Therapeutic effect of erythromycin on influenza virus-induced lung injury in
      mice.
AB  - Erythromycin (EM) is an antibiotic with potent antiinflammatory effects that is
      used for treating chronic lower respiratory tract infections. It has been shown
      that free radicals, such as the superoxide anion and nitric oxide (NO), are
      pathogenic molecules in viral disease. Much attention has been given to a
      critical role of NO in the pathologic events of various inflammatory diseases. In
      the present study, we evaluated the effects of EM on influenza-virus-induced
      pneumonia in mice infected with a lethal dose of influenza virus A/Kumamoto/Y5/67
      (H2N2). The administration of EM at a dose of 3.3 mg/kg/d (intraperitoneally,
      from Days 1 to 6 after infection), significantly improved the survival rate of
      mice infected with influenza virus, and the survival rate of the virus-infected
      mice at Day 20 after infection increased in a dose-dependent fashion with EM
      administered to the animals, from 14% among controls to 42% among animals given
      EM at 1.0 mg/kg/d and 57% among those given EM at 3.3 mg/kg/d. The induction of
      interferon-gamma (IFN-gamma) in the mouse lung was inhibited by EM treatment on
      Day 6 after infection. Simultaneously, the number of inflammatory cells recovered
      in lung lavage fluid 6 d after virus infection was significantly reduced by the
      treatment with EM. The EM treatment resulted in a dose-dependent decrease in the
      level of nitrite/nitrate (metabolites of NO) in the serum and the NO synthase
      (NOS)-inducting potential in the lungs of the virus-infected mice. These results
      indicate that EM may have substantial therapeutic value for various acute
      inflammatory disorders such as influenza-virus-induced pneumonia, by inhibiting
      inflammatory-cell responses and suppressing NO overproduction in the lung.

PMID- 9517603
TI  - Improvement of mild sleep-disordered breathing with CPAP compared with
      conservative therapy.
AB  - The aim of this randomized controlled trial was to assess the effects of
      treatment with continuous positive airway pressure versus conservative therapy
      (CT) on well-being, mood, and functional status in subjects with mild sleep
      disordered breathing (SDB). One hundred and eleven subjects, aged 25 to 65 yr,
      with a respiratory disturbance index (RDI) of 5 to 30 and without subjective
      pathologic sleepiness, were randomized to nasal CPAP or to CT. Ninety-seven
      subjects were followed-up after 8 wk. Treatment response was assessed from
      changes between baseline and follow-up measures of mood, energy/fatigue, and
      functional status/general health. Of the 51 subjects randomized to CPAP, 25 (49%)
      experienced an improved outcome, as compared with 12 of 46 of subjects (26%)
      randomized to CT (p < 0.05). The odds of experiencing a treatment response in the
      CPAP as compared with the CT group were 2.72 (OR: 1.18 to 6.58, 95% CI). A
      beneficial effect of CPAP over CT was most evident among individuals without
      sinus problems and among subjects with hypertension or diabetes. Differential
      treatment responses were not related to degree of baseline sleepiness or SDB.
      This suggests that middle-aged snorers with relatively low levels of SDB (RDI <
      30) may benefit more from nasal CPAP than from less specific therapy directed at
      improving breathing during sleep. CPAP therapy may be beneficial to a broader
      group of subjects than previously appreciated.

PMID- 9517604
TI  - Effect of weight gain on pulmonary function after smoking cessation in the Lung
      Health Study.
AB  - The objective of this study was to determine if the weight gain that accompanies
      smoking cessation is independently associated with reductions in FEV1 and FVC,
      using a multicenter randomized intervention trial of smoking cessation in 10
      communities in the United States and Canada. Enrollees were currently smoking
      women and men 35 to 60 yr of age with mild-to-moderate airway obstruction.
      Participants were randomized to one of three study groups: an intensive smoking
      cessation program with an inhaled bronchodilator (or a placebo), and usual care.
      Changes in absolute and percent predicted FEV1 and FVC between baseline and fifth
      annual follow-up visit were monitored in relation to changes in body weight
      during the interval. At the baseline examination, percent predicted FEV1 was
      maximal at 90 to 100% ideal body weight (IBW) and was lower as body weight
      deviated from this range. The FVC decreased linearly when IBW exceeded 100%.
      Weight gain was greatest during the first 12 mo after smoking cessation. Weight
      gain was associated with lower fifth-year FEV1 and FVC in all smoking categories:
      continuous smokers, intermittent smokers, and sustained quitters. The FVC was
      affected by weight gain more than was the FEV1, and the FEV1 was affected by
      smoking cessation more than FVC. Men showed more impairment of FVC with weight
      gain than did women, possibly because of differential patterns of fat deposition.
      In sustained quitters, after adjustment for baseline factors, the estimated
      reduction of FVC was 17.4 ml/kg weight gain for men and 10.6 ml/kg for women. The
      estimated loss of FEV1 was 11.1 ml/kg weight gain for men and 5.6 ml/kg for
      women. Lung function after smoking cessation is significantly influenced by
      weight gain and affects men more than women. The deleterious effects of weight
      gain are small, however, in comparison with the beneficial effects of smoking
      cessation.

PMID- 9517605
TI  - RANTES induces nasal mucosal inflammation rich in eosinophils, basophils, and
      lymphocytes in vivo.
AB  - RANTES is a CC chemokine that causes chemotaxis of eosinophils, basophils, and
      lymphocytes in vitro. The objective of this study was to investigate the effect
      of RANTES on the influx of inflammatory cells into the nasal mucosa of 12
      allergic patients. In the first phase, each patient was challenged with RANTES or
      diluent on two subsequent days. RANTES caused a significant (p < 0.05) influx of
      eosinophils as compared with the diluent. The number of eosinophils were 5,548 +/
      1,532/ml and 462 +/- 206/ml after RANTES and diluent challenge, respectively, at
      the peak of the response at 2 h. There was also a significant influx of
      metachromatic cells and lymphocytes, but not monocytes, neutrophils, or
      epithelial cells after RANTES challenge. In the second phase, the patients were
      first challenged with an allergen and 24 h later, challenged with RANTES or
      diluent. In the allergen-primed mucosa RANTES induced a significantly higher
      influx of eosinophils, basophils, and lymphocytes. Further, RANTES caused
      migration of monocytes and neutrophils, and shedding of epithelial cells. The
      influx of the inflammatory cells was associated with symptoms of rhinitis. We
      conclude that RANTES induces a clinically symptomatic inflammatory response in
      vivo by causing chemotaxis of eosinophils, basophils, and mononuclear cells.

PMID- 9517606
TI  - Short-term treatment with budesonide does not improve hyperresponsiveness to
      adenosine 5'-monophosphate in COPD.
AB  - The role of inhaled corticosteroids in the treatment of chronic obstructive
      pulmonary disease (COPD) is unclear. We investigated the effects of budesonide on
      airway hyperresponsiveness (AHR) to methacholine (MCh) and adenosine 5'
      monophosphate (AMP), to which we hypothesized the existence of greater
      sensitivity. Additionally, we studied the effects of budesonide on terfenadine
      and ipratropium bromide and on serum levels of interleukin-8 (IL-8) and
      histamine. Forty-four hyperresponsive smokers with moderate to severe COPD
      participated in the study. MCh and AMP challenges were given on three study days,
      after pretreatment with single doses of ipratropium bromide, terfenadine, or
      placebo. Thereafter, subjects were randomized to 6 wk treatment with either 1,600
      microg budesonide or placebo, and the same three study days were repeated.
      Budesonide, as compared with placebo, did not significantly change PC20AMP,
      PC20MCh, or FEV1 after placebo pretreatment. Budesonide increased PC20MCh after
      ipratropium bromide pretreatment, from 5.05 to 10.20 mg/ml (p = 0.036).
      Budesonide decreased serum IL-8 from 9.2 +/- 3.7 to 6.2 +/- 2.1 pg/ml (p <
      0.001). We conclude that AMP did not elicit greater sensitivity than MCh in
      assessing short-term effects of budesonide on AHR in smokers with COPD. We
      suggest that long-term treatment with inhaled corticosteroids might be
      beneficial, by reducing neutrophil load in the airways and improving the action
      of anticholinergic drugs.

PMID- 9517607
TI  - Inhibition of antigen-induced airway hyperresponsiveness by ultralow molecular
      weight heparin.
AB  - Unfractionated heparin (UF-heparin) has been shown to prevent antigen-induced
      airway hyperresponsiveness (AHR), but it is ineffective when administered after
      the antigen challenge. We hypothesized that the failure of UF-heparin to modify
      postantigen AHR might depend on molecular weight. We therefore studied the
      effects of UF-heparin and three low-molecular-weight heparin fractions (medium
      molecular-weight heparin [MMWH]; low-molecular-weight heparin [LMWH]; and
      ultralow-molecular-weight heparin [ULMWH]) on antigen-induced AHR and histamine
      release in bronchoalveolar lavage fluid (BALF). Specific lung resistance (SRL)
      was measured in 20 allergic sheep before, immediately after, and up to 2 h after
      challenge with Ascaris suum antigen. Airway responsiveness was expressed as the
      cumulative provocative dose of carbachol, in breath units, that increased SRL by
      400% (PD400). PD400 was determined before and 2 h after antigen, both without and
      after treatment with aerosolized UF-heparin (1,000 U/kg) and various heparin
      fractions (0.04 mg/kg to 5 mg/kg) administered after the antigen challenge.
      Inhaled UF-heparin (n = 4), MMWH (n = 4), and LMWH (n = 6) failed to modify
      postantigen AHR when administered after the challenge. Only ULMWH (n = 6)
      inhibited postantigen AHR in a dose-dependent manner (percent protection ranged
      from 31% to 139%). In eight additional sheep, histamine in BALF was measured with
      a radioimmunoassay (RIA) before and after the segmental antigen challenge,
      without and after pretreatment with inhaled UF-heparin, LMWH, or ULMWH. Inhaled
      UF-heparin and LMWH inhibited antigen-induced histamine release as measured in
      BALF by 81% and 75%, respectively; whereas ULMWH was ineffective in this respect.
      We conclude that: (1) modification of antigen-induced AHR by fractionated
      heparins is molecular-weight dependent; and (2) only ULMWH attenuates AHR when
      administered after antigen challenge, via an unknown mast-cell-independent
      action.

PMID- 9517608
TI  - Exhaled nitric oxide correlates with airway hyperresponsiveness in steroid-naive
      patients with mild asthma.
AB  - Endogenously released nitric oxide (NO) has been detected in the exhaled air of
      humans. Exhaled NO (NOexh) levels have been significantly increased in patients
      with inflammatory airways disorders such as asthma, and NOexh has been suggested
      to be a usable marker of airway inflammation. In the present study, NOexh levels
      were measured both in steroid-treated and untreated subjects with mild asthma,
      and were correlated with the degree of airway hyperresponsiveness (AHR), measured
      as the dose of histamine that produced a 20% decrease in FEV1 (PC20histamine).
      NOexh levels, which were significantly increased in steroid-naive patients (Group
      A1: NOexh = 21 +/- 11 ppb; n = 56) in comparison with levels in control subjects
      (Group B: NOexh = 10 +/- 2 ppb; n = 20; p < 0.001), correlated significantly with
      the PC20histamine (r = -0.65; p < 0.0001). The NOexh level was significantly
      lower in patients with chronic cough of other causes than bronchial asthma (Group
      A2: NOexh = 11 +/- 3 ppb; n = 18) when compared with the level in subjects with
      mild asthma (Group A1: p < 0.001). Therefore, the noninvasive measurement of
      NOexh allowed us to discriminate, among patients with respiratory complaints,
      between those with and without AHR. In asthmatic subjects treated with inhaled
      steroids, the NOexh levels were significantly lower (Group A3: NOexh = 13 +/- 5
      ppb; n = 25) than in untreated subjects (Group A1; p < 0.01), and there was no
      relationship with the PC20histamine (r = -0.18, p = NS). These findings confirm
      that NOexh reflects AHR in patients with mild asthma who have not already been
      treated with inhaled steroids. Patients treated with inhaled steroids had an
      NOexh level comparable to levels in control subjects, although AHR could still be
      demonstrated.

PMID- 9517609
TI  - Intranasal beclomethasone reduces allergen-induced symptoms and superficial
      mucosal eosinophilia without affecting submucosal inflammation.
AB  - Previous investigations have suggested that nasal secretions, obtained by lavage
      or scraping, and the nasal submucosa, sampled by biopsy, are two distinct
      compartments. We investigated the effect of intranasal corticosteroids on antigen
      induced eosinophil influx into both compartments. We performed a double-blind,
      placebo-controlled study in 15 patients with seasonal allergic rhinitis.
      Beclomethasone dipropionate, 84 microg twice a day, was delivered to one nostril
      while the other nostril received placebo for 1 wk. Subjects were then challenged
      with grass or ragweed extracts on each inferior turbinate. Nasal scrapings from
      both inferior turbinates were obtained before and 24 h after challenge, and
      bilateral inferior turbinate biopsies were obtained 24 h after challenge, with
      the subjects still receiving treatment. Intranasal steroids led to a significant
      reduction in sneezes and eosinophil influx in nasal secretions without affecting
      the number of eosinophils in the submucosa. Furthermore, intranasal steroids had
      no effect on the numbers of submucosal EG2+ (activated eosinophils) or CD25+ (IL
      2-receptor-bearing) cells, nor did they decrease the endothelial expression of
      vascular cell adhesion molecule-1 (VCAM-1). These data show that pretreatment
      with intranasal steroids successfully inhibited the clinical response to allergen
      and reduced eosinophils in the superficial compartment of the nasal mucosa, but
      it had no effect on inflammation in the deeper compartment. This might be related
      to a different distribution of the active medication and antigen into the nasal
      mucosa or to a specific effect of the active medication on the epithelium
      resulting in inhibited migration of eosinophils across this layer.

PMID- 9517610
TI  - Pulmonary hypertension in POEMS syndrome: a new feature mediated by cytokines.
AB  - POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and
      skin changes) syndrome is a rare variant of plasma cell dyscrasia with multiple
      systemic manifestations. We followed the progress of 20 patients with POEMS
      syndrome in our institution over a 10-yr period. Pulmonary hypertension (PH) was
      observed in five patients. All patients suffered dyspnea on exertion, which
      always appeared during an exacerbation of POEMS syndrome. The typical
      echocardiographic signs of PH were observed in all of these patients, and the
      median pulmonary-artery systolic pressure was 57 mm Hg (range, 50 to 65 mm Hg).
      Mean pulmonary-artery pressure during right side heart catheterization in two
      patients was 32 mm Hg. No other explanation for the PH could be found.
      Overproduction of cytokines was found in all cases, with high serum
      concentrations of interleukin-1beta, interleukin-6, tumor necrosis factor-alpha,
      and vascular endothelial growth factor. We suggest that PH should be added to the
      list of symptoms of POEMS syndrome. Cytokines may mediate POEMS syndrome
      associated PH, as proposed for the other systemic manifestations of this
      disorder.

PMID- 9517612
TI  - Diazepam suppresses sleep apneas in rats.
AB  - To test the respiratory effects of benzodiazepines in an established animal model
      of central apnea, we administered nonhypnotic and hypnotic doses of diazepam to
      nine adult male Sprague-Dawley rats chronically instrumented for sleep staging.
      In random order on separate days, rats were recorded following intraperitoneal
      injection of: (1) saline; (2) 0.05 mg/kg diazepam; or (3) 5 mg/kg diazepam.
      Normalized inspiratory minute ventilation increased significantly during
      wakefulness and non-rapid eye movement (non-REM) sleep following each dose of
      diazepam (p < 0.003 in each case) and following the highest dose during rapid eye
      movement (REM) sleep (p = 0.01). In accord with this respiratory stimulation, non
      REM-related spontaneous and post-sigh apnea expression decreased following each
      dose of diazepam (p = 0.006 to 0.04), but REM-related apnea expression was
      unaffected despite significant respiratory stimulation. The durations of non-REM
      and REM sleep were unaffected by the low dose, but following 5 mg/kg of diazepam
      non-REM sleep was increased (p = 0.03) and REM sleep was decreased (p = 0.009).
      We conclude that both hypnotic and non-hypnotic doses of benzodiazepines may be
      associated with suppression of sleep-related central apnea. We further conclude
      that non-REM and REM-related apneas arise from at least partially distinct
      mechanisms.

PMID- 9517611
TI  - Recurrent Pseudomonas aeruginosa pneumonia in ventilated patients: relapse or
      reinfection?
AB  - A prospective observational study was performed to determine whether recurrent
      episodes of pneumonia caused by Pseudomonas aeruginosa in ventilated patients
      were due to a relapse of the previous clone or to reinfection with a new one.
      Diagnosis was based on quantitative cultures of secretions obtained by
      bronchoscopy. Comparison of strains was made by chromosomal fingerprinting based
      on pulsed field gel electrophoresis (PFGE). Thirty-three (89.1%) of 37 patients
      survived the initial week after pneumonia diagnosis; six survivors (18.1%) had
      multiple episodes caused by the same species. Presence of adult respiratory
      distress syndrome (83.3% versus 22.2%, p = 0.02) was the only factor
      significantly associated with clinical recurrences. The 16 isolates from five
      patients (nine recurrences) were analyzed by PFGE. All new isolates from
      recurrent episodes, excepting one, were considered as relapses. These data
      suggest that most recurrent episodes of P. aeruginosa pneumonia in ventilated
      patients occur due to persistence of strains present in a prior infection.

PMID- 9517613
TI  - Lung growth and maturation after tracheal occlusion in diaphragmatic hernia.
AB  - Tracheal occlusion (TO) was performed at 120 d of gestation by noninvasive
      endoscopic technique using a releasable latex balloon, in fetal lambs with
      diaphragmatic hernia (DH) established at 85 d. The lungs were studied at 139 d in
      five fetuses with DH + TO, five fetuses with DH only, and six control fetuses.
      Fluid retention consecutive to TO allowed fetal lungs to grow. Histological
      pulmonary structure was more mature in DH + TO than in DH alone. The growth
      inducing effect of TO was however incomplete, with an increased protein/DNA
      ratio. Tissue phospholipids were increased, but this was not reflected in the
      surfactant compartment. The major surfactant component, disaturated
      phosphatidylcholine, was reduced to 58% of its control value in DH, and further
      reduced to 17.5% of its control value in DH + TO. The proportion of surfactant
      protein B immunoreactive cells, assumed to represent the proportion of type II
      cells, was increased in DH (27% of all parenchymal cells), and reduced in DH + TO
      (7.8%) as compared with control fetuses (15%). In conclusion, although
      noninvasive tracheal occlusion in utero is feasible and may partly compensate the
      adverse effects of DH on lung organogenesis, it reduces the number of type II
      cells and induces a dramatic surfactant deficit. Using this technique in human
      fetuses requires careful consideration until further evaluation of lung
      functional characteristics has been achieved in this experimental model.

PMID- 9517614
TI  - Airway inflammation in young marijuana and tobacco smokers.
AB  - Forty healthy young subjects, ages 20 to 49 yr, underwent videobronchoscopy,
      mucosal biopsy, and bronchial lavage to evaluate the airway inflammation produced
      by habitual smoking of marijuana and/or tobacco. Videotapes were graded in a
      blinded manner for central airway erythema, edema, and airway secretions using a
      modified visual bronchitis index. The bronchitis index scores were significantly
      higher in marijuana smokers (MS), tobacco smokers (TS), and in combined
      marijuana/tobacco smokers (MTS), than in nonsmokers (NS). As a pathologic
      correlate, mucosal biopsies were evaluated for the presence of vascular
      hyperplasia, submucosal edema, inflammatory cell infiltrates, and goblet cell
      hyperplasia. Biopsies were positive for two of these criteria in 97% of all
      smokers and for three criteria in 72%. By contrast, none of the biopsies from NS
      exhibited greater than one positive finding. Finally, as a measure of distal
      airway inflammation, neutrophil counts and interleukin-8 (IL-8) concentrations
      were determined in bronchial lavage fluid. The percentage of neutrophils
      correlated with IL-8 levels and exceeded 20% in 0 of 10 NS, 1 of 9 MS, 2 of 9 TS,
      and 5 of 10 MTS. We conclude that regular smoking of marijuana by young adults is
      associated with significant airway inflammation that is similar in frequency,
      type, and magnitude to that observed in the lungs of tobacco smokers.

PMID- 9517615
TI  - Antibody to E- and L-selectin does not prevent lung injury or mortality in septic
      baboons.
AB  - Recruitment of polymorphonuclear leukocytes (PMN) through upregulation of
      cellular adhesion molecules is a proposed mechanism of injury in sepsis and acute
      respiratory distress syndrome (ARDS). We hypothesized that pretreatment of
      baboons with a monoclonal antibody to human E- and L-selectin (EL-246) during
      sepsis would decrease PMN influx into tissues and result in less organ injury
      during gram-negative sepsis. We studied 14 anesthetized, ventilated adult
      baboons; six animals received 1 mg/kg of EL-246 before infusion of an LD100 of
      live Escherichia coli and six received the E. coli infusion without antibody
      therapy. Two other animals received 1 mg/kg of EL-246 intravenously without an
      infusion of bacteria. Intermittent measurements were made of circulatory
      pressures, cardiac output, urine output, arterial blood gases,
      ventilation:perfusion ratio (VA/Q), and hematologic status. The experiments were
      ended at 48 h or at the time of death. Tissues were harvested for pathology and
      biochemical measurements. The E. coli infusions were associated with a
      hyperdynamic state, pulmonary hypertension, systemic hypotension, decreased urine
      output (UOP), and metabolic acidosis. The antibody partly blocked PMN migration,
      but there were few significant physiologic or biochemical differences between the
      EL-246-treated and untreated animals. In the antibody-treated animals, UOP was
      decreased, metabolic acidosis was worsened, and median survival time was
      decreased significantly. We conclude that treatment with an antibody to E- and L
      selectin in gram-negative sepsis does not improve gas exchange or protect against
      lung injury, and is associated with decreased survival time in primates.

PMID- 9517617
TI  - Vitamin D binding protein variants and the risk of COPD.
AB  - Although the development of chronic obstructive pulmonary disease (COPD) in
      smokers shows genetic susceptibility, only alpha1-antitrypsin deficiency has been
      identified as a definite genetic risk factor. There have been three previous
      studies in which associations between Gc-globulin phenotypes and COPD have been
      investigated. Although some data suggest an association, the results were
      inconclusive. Because smoking is the major risk factor for COPD, it may have been
      a confounding factor in previous studies. We have investigated Gc-globulin
      genotypic frequencies among 75 COPD patients and 64 nonobstructed controls. Both
      groups had significant smoking histories: pack-years (mean +/- SD) of 52 +/- 30
      and 48 +/- 27, respectively. The results show that homozygosity for the Gc2
      allele is protective against COPD (OR = 0.17, 95% CI = 0.03 to 0.83). There were
      no differences between genotypes for lung elastic recoil values or for the level
      of upstream airway resistance. Gc-globulin can enhance complement (C5a)-mediated
      neutrophil chemotaxis. Because neutrophils play a role in parenchymal destruction
      and airway inflammation, we examined whether Gc-globulin's ability to enhance
      neutrophil chemotaxis varied with genotype. We found no difference among
      genotypes with respect to neutrophil chemotaxis suggesting that the protective
      effect of the Gc2 allele is mediated through a different mechanism.

PMID- 9517616
TI  - Haemophilus influenzae in lung explants of patients with end-stage pulmonary
      disease.
AB  - In order to determine the presence and distribution of Haemophilus influenzae in
      lung tissue sections, we obtained lung explants from 49 lung transplant
      recipients with cystic fibrosis (CF) (n = 16), chronic obstructive pulmonary
      disease (COPD) including emphysema (n = 16), bronchiectasis (n = 5), pulmonary
      hypertension (n = 9), Langerhans cell histiocytosis (n = 1), and idiopathic
      pulmonary fibrosis (n = 2). Analysis was done by selective culturing,
      immunoperoxidase (IP) staining, and by polymerase chain reaction (PCR). H.
      influenzae was cultured from specimens of the lung explants from one CF and one
      COPD patient. IP staining of tissue sections was positive in 24 patients (10 CF
      patients, eight COPD patients, two bronchiectasis patients, and four patients
      with noninfectious pulmonary diseases). IP-positive tissue sections were PCR
      positive, and IP-negative sections were PCR-negative. H. influenzae was more
      frequently detected in tissue sections of lung explants from CF and COPD patients
      than from patients with bronchiectasis or noninfectious pulmonary diseases. H.
      influenzae was diffusely present in the epithelium, the submucosa of the bronchi,
      the bronchioles, the interstitium, and the alveolar epithelium. H. influenzae was
      localized extracellularly alone and in bacterial clusters, and was also
      associated with macrophages in CF patients. The results of this study demonstrate
      that H. influenzae is often present in the lungs of patients with end-stage
      pulmonary disease, especially CF and COPD patients. H. influenzae is diffusely
      present in the respiratory epithelium and subepithelial layers of the lungs of
      these patients.

PMID- 9517618
TI  - Clara cell protein (CC16) in pleural fluids: a marker of leakage through the
      visceral pleura.
AB  - Pleural fluid (PF) proteins either derive from serum by diffusion or are locally
      secreted within the pleural space. Another hypothetical origin is a leakage of
      lung secretory proteins across the visceral pleura. To test this hypothesis, we
      investigated the occurrence, sources, and determinants in PF of CC16, a small
      size and readily diffusible protein of 16 kDa secreted by bronchiolar Clara
      cells. CC16 concentration was determined by a sensitive latex immunoassay in
      serum and PF of 117 subjects (86 exudates and 31 transudates) and, for purpose of
      comparison, in ascites samples from another group of 38 subjects (7 exudates and
      31 transudates). CC16 was also studied in serum and PF of normal rats and in rats
      with pleural exudate induced by alpha-naphthyl-thiourea (ANTU). The levels of
      CC16 in PF and ascites were highly correlated with that in serum, suggesting a
      diffusional exchange across the pleural/blood and peritoneal/blood barriers.
      Whereas CC16 occurs at similar levels in ascites and serum, the protein was found
      to be more concentrated in PF than in serum in both humans (geometric mean in
      microg/L, 26.2 versus 14.6, p < 0.0001) and rats (213 versus 16.2, p < 0.001). A
      local synthesis of CC16 appeared unlikely in view of the lack of CC16
      immunostaining in pleura of both species. The only plausible explanation for
      these findings is that CC16 in PF originates from two sources: diffusion from
      plasma and a leakage from the lung into the pleural space across the
      semipermeable visceral pleura. This interpretation is supported by a markedly
      increased leakage of CC16 in experimental exudates induced by ANTU and the
      finding of high CC16 concentrations in human transudates associated with
      congestive heart failure, two conditions wherein PF has been shown to arise from
      the interstitial spaces of the lung.

PMID- 9517619
TI  - Proliferation of airway epithelium after ozone exposure: effect of apocynin and
      dexamethasone.
AB  - Ozone is an environmental pollutant with potent oxidizing properties. We
      investigated whether exposure to ozone-induced cell proliferation in the lungs of
      rats, and determined the effect of an antioxidant and of a glucocorticosteroid in
      Brown-Norway (BN) rats. Following single ozone exposure (0.5, 1.0, or 3.0 ppm for
      6 h), proliferating cell nuclear antigen (PCNA) expression, as determined with
      immunohistochemistry, was significantly increased in the bronchial epithelium and
      alveolar epithelium as compared with controls exposed to filtered air with a
      maximal effect at 24 to 48 h (p < 0.001). Apocynin (5 mg/kg, orally), a reduced
      nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor, reduced
      the PCNA index in bronchial epithelium induced by ozone (3 ppm, 6 h) from 11.5 +/
      1.3% (percent of nuclear cells expressing PCNA) to 4.4 +/- 1.3% (mean +/- SEM; p
      < 0.05). Dexamethasone (3 mg/kg, intraperitoneally) also reduced the PCNA index
      in bronchial epithelium, from 19.2 +/- 2.3% to 10.9 +/- 2.6% (p < 0.05).
      Dexamethasone but not apocynin inhibited ozone-induced neutrophil influx. Rats
      exposed repeatedly to ozone (3.0 ppm, 3 h, on three occasions 48 h apart)
      expressed a lower PCNA index in bronchial epithelium than did rats exposed only
      once at 1.9 +/- 0.7% versus 6.0 +/- 0.9%, respectively (p < 0.05). The
      proliferative epithelial response following a single exposure to ozone is
      modulated through oxidative and inflammatory mechanisms probably involving
      neutrophils.

PMID- 9517620
TI  - Risks and routes for ventilator-associated pneumonia with Pseudomonas aeruginosa.
AB  - In a prospective study, we screened specimens from 190 mechanically ventilated
      patients hospitalized in a surgical intensive care unit, and from the environment
      to assess risks and routes of colonization/infection. Specimens from various
      sites were collected on admission and once a week throughout each patient's stay.
      All P. aeruginosa isolates were typed by determination of DNA patterns. Data were
      collected from patients to identify risk factors. In vitro production of
      exoenzymes of different strains were compared. Forty-four patients were colonized
      with P. aeruginosa on the bronchopulmonary tract and 13 suffered from pneumonia.
      The 7-d and 14-d Kaplan-Meier rates of colonization were 2.21 and 7.03%. Twenty
      one patterns of bronchopulmonary tract isolates were isolated from single
      patients and 10 from several patients. The lower airway was often the first site
      of colonization. The contribution of environment to patient colonization appeared
      to be small. The length of hospitalization, the previous use of third-generation
      cephalosporins less effective against P. aeruginosa, and chronic obstructive
      pulmonary disease were the most significant predictors of colonization/infection.
      The in vitro exoprotein production was not correlated with the presence of
      pneumonia. Our study may be useful in identifying which patients in the
      mechanically ventilated population are at greater risk of P. aeruginosa
      pneumonia.

PMID- 9517621
TI  - Pulmonary manifestations of Gaucher disease: an increased risk for L444P
      homozygotes?
AB  - Pulmonary disease is a complication of Gaucher disease (GD), a lysosomal disorder
      due to the deficiency of glucocerebrosidase. Lung involvement was investigated
      through chest radiography, high-resolution computed tomography of the chest,
      pulmonary function tests (PFT), and oxygen saturation (SaO2) at 21% FI(O2) in 13
      Italian GD patients, six homoallelic for the L444P mutation (Group A), seven with
      various genotypes (Group B). Echocardiography and transcutaneous oxygen tension
      measurement at room air and after breathing 100% oxygen were performed to exclude
      pulmonary hypertension and/or intrapulmonary shunts. A score index (SI) including
      lung involvement evaluated the severity of GD. In three Group A patients with
      respiratory symptoms and in an asymptomatic male interstitial involvement was
      demonstrated; one child died of aspiration pneumonia. Group B patients had no
      signs of lung damage; PFT were normal in all cases but one. SaO2 was normal in
      both groups. Pulmonary vascular disease was ruled out in three cases with
      respiratory symptoms. In Groups A and B the median SI were 22 and 13,
      respectively (p < 0.01). L444P homozygotes appear at major risk for developing
      pulmonary disease, even at earlier ages. A comprehensive evaluation of lung
      involvement is recommended primarily in these subjects.

PMID- 9517622
TI  - Variability of peripheral blood lymphocyte beta-2-adrenergic receptor density in
      humans.
AB  - Beta2-adrenergic receptor (betaAR) density on peripheral blood lymphocytes has
      been used as an index to reflect the betaAR state of the body. Lymphocytes
      betaARs are unequally distributed among lymphocyte subpopulations, with the
      highest density on CD8+ cells and the lowest on CD4+ cells. Thus, the measurement
      of peripheral blood lymphocyte betaAR density could vary with changes in CD4+ and
      CD8+ cell concentrations. We examined the individual and intersubject variance of
      betaAR density and lymphocyte subpopulations over time in 10 normal subjects,
      studied on 3 to 5 different d always at approximately 9:00 A.M. over a 4- to 12
      wk period. Peripheral blood lymphocytes were isolated and beta2-adrenergic
      receptor density was determined by specific binding of [125I]-(-)iodopindolol,
      and lymphocyte subpopulations were measured by flow cytometry. Average receptors
      per lymphocyte were 776 +/- 183. Whereas the absolute values of CD4+% and CD8+%
      cell concentrations varied little in individual subjects (coefficient of
      variation 9.5% and 11.1%, respectively), the individual betaAR variance was
      greater (coefficient of variation 22.4%). However there was a significant
      correlation between betaAR and CD4+% and CD8+% cell concentration (correlation
      coefficients: -0.58, p < 0.001; +0.51, p < 0.001, respectively). This information
      is relevant to interpretations of changes in peripheral betaAR in humans.

PMID- 9517623
TI  - Measurement of endogenous nitric oxide in the lungs of patients with the acute
      respiratory distress syndrome.
AB  - Elevated levels of nitric oxide (NO) are detectable in the exhaled breath of
      patients suffering from a number of inflammatory lung diseases. We hypothesized
      that NO would be detectable in the exhaled air of patients with the acute
      respiratory distress syndrome (ARDS) undergoing mechanical ventilation and that
      the concentration would be greater than that from a control group of ventilated
      subjects. The concentration of NO in the lower airways of 13 patients with ARDS
      and 18 patients anesthetized and ventilated prior to cardiac surgery was measured
      by chemiluminescence. The NO concentration was 1.13 +/- 0.36 (mean +/- SEM) parts
      per billion (ppb) in the ARDS group and 5.5 +/- 0.8 ppb in the control group (2 p
      < 0.0001). NO is detectable in the exhaled air of patients with ARDS and is at a
      lower concentration than in control subjects.

PMID- 9517624
TI  - Exhaled nitric oxide in chronic obstructive pulmonary disease.
AB  - Chronic obstructive pulmonary disease (COPD) is characterized by progressive
      airflow obstruction and a neutrophilic inflammation. Exhaled nitric oxide (NO)
      may be a marker of disease activity in a variety of lung diseases. We measured
      exhaled NO in patients with documented COPD and investigated whether the
      concentration of exhaled NO is related to the severity of disease as defined by
      lung function. We also investigated whether concentration of exhaled NO was
      different in COPD patients who received inhaled steroids compared with steroid
      naive patients. We studied 13 current smokers with COPD, eight exsmokers with
      COPD, 12 patients with unstable COPD (exacerbation or severe disease), and 10
      smokers with chronic bronchitis without airflow limitation. Exhaled NO levels
      were significantly higher in patients with unstable COPD (12.7 +/- 1.5 ppb) than
      in other groups (p < 0.01). Exhaled NO levels were significantly higher in
      smokers with COPD than in smokers with chronic bronchitis (4.3 +/- 0.5 versus 2.5
      +/- 0.5 ppb, p < 0.05), and were even higher in patients with COPD who had
      stopped smoking (6.3 +/- 0.6 ppb, p < 0.01). Exhaled NO levels showed a
      significant negative correlation with their lung function assessed by % predicted
      FEV1 values (r = -0.6, p < 0.001). Exhaled NO levels in patients treated with
      inhaled steroids were significantly higher compared with steroid-naive patients
      (8.2 +/- 1.2 ppb versus 5 +/- 0.4 ppb, p < 0.05), but the first group included
      more severe patients as assessed by lung function. We conclude that exhaled NO
      could serve as a useful, practical marker for monitoring disease activity in
      COPD.

PMID- 9517625
TI  - Mental stress and peptic ulcers: an earthshaking association.

PMID- 9517626
TI  - How to treat the cytomegalovirus troll.

PMID- 9517627
TI  - Immunological tests to monitor inflammatory bowel disease--have they delivered
      yet?

PMID- 9517628
TI  - Past is prologue.

PMID- 9517629
TI  - Helicobacter pylori--more light, less heat.
AB  - Several areas of broad agreement exist concerning the management of specific
      patient groups with clear-cut complications of H. pylori-colonization. Other
      aspects of this infection remain less well defined. These include the mode of
      transmission and pathogenesis of H. pylori, the clinical management of patients
      who do not have ulcer disease, and the approach to populations at risk of the
      clinical consequences of this bacterium. This review focuses on the unresolved
      issues of H. pylori infection that are of concern to the clinical
      gastroenterologist.

PMID- 9517630
TI  - Peptic ulcers after the Hanshin-Awaji earthquake: increased incidence of bleeding
      gastric ulcers.
AB  - OBJECTIVE: Although physical stresses are known to induce peptic ulcers in the
      upper gastrointestinal tract, it remains controversial whether emotional stress
      can cause peptic ulcers. Therefore, we examined retrospectively the influence of
      the Hanshin-Awaji earthquake that occurred in Japan in January 1995 on the
      occurrence of peptic ulcer disease among noninjured residents. METHODS: Sixty-one
      hospitals, covering 70% of all endoscopy examinations performed in this area,
      joined the study and were divided into three areas according to the severity of
      the damage. A comparison was made between a group of 10,831 patients who
      underwent upper gastrointestinal endoscopy within 2 months after the earthquake
      and 16,100 who did so in the same hospitals during the corresponding period in
      1994. RESULTS: In the most devastated area, in spite of a dramatic decrease in
      the total number of endoscopies (50.0%), patients with gastric ulcer (GU) were
      increased in 1995, whereas those with duodenal ulcer were decreased, resulting in
      a higher ratio of gastric to duodenal ulcers than in 1994 (3.07 vs 1.88). In
      particular, there was a marked increase in bleeding GU. The mean age of patients
      with GU was significantly higher in 1995 than in 1994. CONCLUSION: The Hanshin
      Awaji earthquake-induced life event stress not only triggered but also
      exacerbated GU, particularly in the elderly.

PMID- 9517632
TI  - The circulating common gamma chain (CD132) in inflammatory bowel disease.
AB  - OBJECTIVE: Inflammatory bowel disease (IBD) is characterized by T cell
      activation. Activated T cells shed interleukin-2 receptors (IL-2R) in a soluble
      form. A positive correlation between sIL-2Ralpha (CD25) and disease activity is
      well documented in IBD, whereas IL-2Rgamma (CD132) has not been investigated in
      this respect. Sera from 42 patients with ulcerative colitis (UC), 34 with Crohn's
      disease (CD), 31 healthy volunteers, and 12 patients with infectious
      enterocolitis were obtained. METHODS: Disease activity was scored according to a
      semiquantitative score for UC and CD. sIL-2R alpha chain and gamma chain were
      assessed by sandwich ELISA techniques using monoclonal antibodies specific for
      CD25 and CD132, respectively. RESULTS: The concentration of IL-2Ralpha chain
      (CD25) was found to be median 3.8 ng/ml in healthy volunteers versus 7.0 ng/ml in
      UC patients (p < 0.001), and 9.6 ng/ml in CD patients (p < 0.001). With respect
      to IL-2Rgamma (CD132), significantly higher amounts were found in CD patients:
      6.6 ng/ml as compared with healthy controls <1.0 ng/ml (p < 0.004). A Kruskal
      Wallis test revealed a significant correlation between alpha chain and disease
      activity in CD (p < 0.001), and further significantly higher gamma chain levels
      were found in active CD (p = 0.03). For UC patients, a statistically significant
      increase of the alpha chain with increasing disease activity (p < 0.01) was
      observed, whereas no significant changes of the gamma chain levels were found (p
      > 0.05). A difference of gamma chain levels were found between CD and UC in
      moderate and severe disease activity (p < 0.05). Further analyses revealed that
      mesalazine did not influence the IL-2Ralpha or -gamma concentration either in UC
      or in CD patients. CONCLUSION: An increased circulating level of the soluble
      common gamma chain (CD132) seems to be found in CD, and an overlap exists between
      CD and UC.

PMID- 9517631
TI  - Treatment of cytomegalovirus esophagitis in patients with acquired immune
      deficiency syndrome: a randomized controlled study of foscarnet versus
      ganciclovir. The Italian Cytomegalovirus Study Group.
AB  - OBJECTIVE: Although several uncontrolled studies have shown that the response
      rate to ganciclovir and foscarnet for all forms of cytomegalovirus (CMV)
      infection in immunocompromised patients is almost similar, to date, no controlled
      clinical trial has been specifically designed to compare these two agents in the
      treatment of CMV esophagitis. The aim of this study was, therefore, to compare
      the efficacy and safety of these two drugs in the induction therapy of CMV
      esophagitis in patients with acquired immunodeficiency syndrome (AIDS). METHODS:
      Thirty-nine of 211 (18%) consecutive AIDS patients undergoing endoscopy for
      esophageal symptoms had macroscopic esophagitis that proved to be sustained by
      CMV based on the documentation of typical intranuclear inclusions at histology;
      23 were considered eligible for this study and were randomized to receive
      foscarnet 90 mg/kg b.i.d. or ganciclovir 5 mg/kg b.i.d. for 21 days. Twelve
      patients received foscarnet, whereas 11 were treated with ganciclovir. Clinical
      and laboratory evaluation was performed weekly, and endoscopy was repeated at the
      end of therapy. The two treatment groups were well balanced as to the following
      characteristics at entry: age, sex, absolute number of CD4 cells, duration of
      AIDS, Karnofsky score, frequency of concomitant Candida esophagitis (grade I or
      II), and severity of esophageal symptoms. RESULTS: Marked endoscopic improvement
      (complete disappearance of macroscopic lesions or significant reduction of the
      endoscopic score) was observed in eight of 11 (73%) of foscarnet and seven of 10
      (70%) of ganciclovir-treated patients, and inclusion bodies disappeared from
      follow-up biopsies in 55% and 50% of patients, respectively. The symptomatic
      response was also similar for both treatments: 82% of patients who received
      foscarnet and 80% of those treated with ganciclovir had a complete or at least a
      good clinical response. Frequency of adverse events was comparable with both
      drugs: only one patient in each group suspended treatment because of severe side
      effects. CONCLUSIONS: Foscarnet and ganciclovir appear to be similarly effective
      and safe in the induction therapy of AIDS-related CMV esophagitis. Consequently,
      the choice of the anti-CMV agent should be tailored to the individual patient
      according to the different toxicity profiles of the two drugs.

PMID- 9517633
TI  - The impact of health care reform on gastroenterology fellows: are training
      programs preparing them for the future? American College of Gastroenterology
      Educational Affairs Subcommittee on Training.
AB  - OBJECTIVE: Health care reform is dramatically changing the practice and delivery
      of medical care. The goal of this investigation was to examine gastroenterology
      trainees' outlook on the impact of health care reform on training programs.
      METHODS: A 24-question survey was mailed in February 1996 to 780 GI fellows
      obtained from the comprehensive American College of Gastroenterology (ACG)
      database. RESULTS: A total of 362 fellows responded (46%): 85% were male, 57%
      Caucasian, 75% married, and 86% were university-based. Ninety-six percent of
      fellows believed that health care reform is adversely affecting the quality of
      health care and 94.1% felt that it was adversely affecting fellowship training.
      Eighty-eight percent expressed concern over the impact of health care reform on
      practice opportunities. Only 9% of fellows reported that their training program
      had established a specific educational program addressing health care reform,
      whereas 83% of fellows felt that their program should do so. CONCLUSION:
      Gastroenterology fellows are concerned about the impact of health care reform on
      the quality of care and the quality of their fellowship training. Trainees
      believe that programs are not providing sufficient education to help them respond
      to the changes in health care.

PMID- 9517634
TI  - Squamous islands in Barrett's esophagus: what lies underneath?
AB  - OBJECTIVE: Squamous islands are frequently visualized at the time of upper
      endoscopy in patients with Barrett's esophagus, especially those on proton pump
      inhibitor therapy (PPI). The significance of these islands is not clearly
      understood. The aim of this study was to systematically biopsy macroscopic
      squamous islands and to examine their histologic characteristics. METHODS:
      Patients with Barrett's esophagus undergoing surveillance had squamous islands
      documented and biopsied at the time of endoscopy. Barrett's esophagus was defined
      as the presence of a columnar lined esophagus on endoscopy with intestinal
      metaplasia on biopsy. All biopsies were obtained by a single senior endoscopist
      and were stained with alcian blue at pH 2.5. Biopsy samples with inadequate
      tissue quantity were not included in the study. RESULTS: A total of 39 biopsies
      were obtained from 22 patients. Twenty of the 22 patients were male, with a mean
      age of 65.4 yr (range 47-80 yr). The mean length of Barrett's mucosa was 5.6 cm
      (range 1-11 cm). Eleven of 22 patients were on omeprazole (mean dose 29.1
      mg/day), whereas seven patients were on lansoprazole (60 mg/day). The mean
      duration of PPI therapy was 2.3 yr (range 9-71 months) at the time of biopsy of
      the squamous islands. Three patients were on H2-blocker therapy whereas the
      remaining patient had not been started on acid suppression therapy. On histology,
      24 biopsy specimens (61.5%) revealed only squamous epithelium, whereas 15 (38.5%)
      showed the presence of intestinal metaplasia underlying the squamous epithelium.
      There was no significant difference between the patients with and without
      underlying intestinal metaplasia in regard to age, Barrett's length, dose, and
      duration of PPI therapy. CONCLUSION: In more than one-third of biopsies of
      macroscopic squamous islands within Barrett's esophagus, microscopic intestinal
      metaplasia is detected. The presence of squamous islands should not be equated
      with regression of Barrett's esophagus or with decreased cancer risk.

PMID- 9517635
TI  - Early indicators of prognosis in upper gastrointestinal hemorrhage.
AB  - OBJECTIVE: Endoscopy allows accurate risk stratification of patients presenting
      with gastrointestinal bleeding; frequently, however, it is not immediately
      available. Initial management and triage of patients thus depends on
      nonendoscopic information. We sought to risk stratify patients with upper
      gastrointestinal bleeding using variables available on initial presentation (ie.,
      before endoscopy). METHODS: A retrospective observational study was performed
      using data from 335 admissions with an initial diagnosis of upper
      gastrointestinal hemorrhage. All patients underwent endoscopy and were evaluated
      for an adverse outcome during their hospitalization. An adverse outcome was
      defined as death, the need for any operation, recurrent hematemesis, recurrent
      melena after initial clearing, or a hematocrit falling despite transfusion.
      RESULTS: Univariate analysis identified 17 distinct variables associated (p <
      0.05) with an adverse outcome. A stepwise logistic regression identified five
      variables as independent predictors (p < 0.05) of an adverse outcome: an initial
      hematocrit <30%, initial systolic blood pressure < 100 mm Hg, red blood in the
      nasogastric lavage, history of cirrhosis or ascites on exam, and a history of
      vomiting red blood. We derived a decision rule based on patients having 0-5 of
      these independent predictors. This decision rule allowed identification of a
      large patient population with a <10% chance of an adverse outcome. CONCLUSION:
      Risk stratification is possible from information available at the time of initial
      presentation. If confirmed in other populations, these predictors can be used to
      identify patients who require a less intensive level of care.

PMID- 9517637
TI  - Hepatic iron concentration in hereditary hemochromatosis does not saturate or
      accurately predict phlebotomy requirements.
AB  - OBJECTIVE: Biochemical measurement of the hepatic iron concentration (HIC) is
      essential for the diagnosis of hereditary hemochromatosis (HH). The aim of this
      study was to determine whether the HIC at the time of diagnosis could predict the
      subsequent phlebotomy requirements and to determine whether saturation of HIC
      occurred in HH. METHODS: Fifty-four patients (32 male, 22 female) with homozygous
      HH were evaluated, and HIC was measured in liver biopsies. Patients were
      subjected to weekly phlebotomy (500 ml) until the transferrin saturation was <50%
      and/or the serum ferritin concentration was <50 microg/L. The relationship
      between HIC and total body iron stores (as measured by phlebotomy requirements)
      was determined using both linear and nonlinear (sigmoidal model) least squares
      regression. RESULTS: The HIC ranged from 3,742 to 41,040 microg/g dry wt. A
      linear relationship between HIC and total body iron stores (iron removed, IR, g)
      best described the data both in male (HIC = 1986 IR - 3494; r = 0.83; p < 0.001)
      and female HH patients (HIC = 1251 IR + 2690; r = 0.75; p < 0.001). Men required
      eight more phlebotomies (2 g iron) on average, compared with women, to reach
      normal iron stores. There was no evidence of saturation of hepatic iron levels at
      higher total body iron stores. However, accurate prediction of individual
      phlebotomy requirements based on the HIC or serum ferritin concentration at the
      time of diagnosis was not possible. CONCLUSION: The phlebotomy requirement for
      treatment of HH cannot be accurately predicted from the initial HIC or serum
      ferritin level. Within the range examined, hepatic iron deposition did not
      saturate in HH.

PMID- 9517636
TI  - Association of esophageal dysfunction and pulmonary function impairment in
      systemic sclerosis.
AB  - OBJECTIVE: The aim of this study was to investigate the relationship between
      esophageal dysfunction and pulmonary involvement in patients with systemic
      sclerosis (SSc). METHODS: Pulmonary function parameters were compared between
      groups of patients with and without manometric evidence for SSc-induced
      esophageal dysmotility. RESULTS: Twenty-six of 43 patients (60.5%) exhibited a
      marked hypo- or aperistalsis of the smooth muscle portion of the esophagus. Total
      lung capacity, inspiratory vital capacity, and forced vital capacity were
      significantly lower in patients with esophageal dysfunction compared with those
      with normal esophageal peristalsis (p < 0.001). Patients with the diffuse form of
      SSc (n = 20) had significantly lower values for total lung capacity and
      inspiratory vital capacity compared with patients with the limited type of SSc (n
      = 23; p < 0.05). CONCLUSION: There is a significant association of esophageal
      dysmotility with reduced lung volumes in SSc. Possible explanations for these
      findings are pulmonary damage due to increased gastroesophageal reflux and, more
      likely, simultaneous involvement of the lungs and the esophagus in the disease
      process.

PMID- 9517638
TI  - Laparoscopic antireflux surgery in the elderly.
AB  - OBJECTIVE: Laparoscopic antireflux surgery is indicated in young patients with
      medication-dependent gastroesophageal reflux disease (GERD), both because of
      their need for lifelong medical treatment and the need to prevent the
      complications of GERD. Many elderly patients with GERD have similar concerns. We
      compared the safety and efficacy of laparoscopic antireflux surgery in the
      elderly with the results achieved in patients <65 yr. METHODS: A total of 359
      patients have had laparoscopic antireflux surgery in our hospital, 42 of whom
      were > or = 65 yr of age. Symptoms were scored from 0 (none) to 4 (severe) before
      and after surgery. Ambulatory pH monitoring was also performed before and after
      surgery. Results were compared between age groups with the Mann-Whitney U test.
      RESULTS: Elderly patients had significantly higher preoperative American Society
      of Anesthesiologists (ASA) scores (mean 2.4 vs 2.0) (p = 0.0024), but otherwise
      there were no significant differences in preoperative symptom scores or pH
      results. Both groups demonstrated equivalent postoperative improvement in
      symptoms and 24-h pH study. There was no mortality in either group, and there was
      no significant difference in morbidity or hospital stay between the two groups.
      CONCLUSION: Laparoscopic antireflux surgery is a safe and effective treatment of
      GERD in the elderly and should not be refused solely on the basis of age.

PMID- 9517640
TI  - Bilirubinate granules: main pathologic bile component in patients with idiopathic
      acute pancreatitis.
AB  - OBJECTIVE: The aim of this study was to evaluate the main pathologic component of
      bile obtained by biliary drainage in patients with acute idiopathic pancreatitis
      and therapeutic implications. METHOD: Eighteen patients diagnosed with idiopathic
      acute pancreatitis underwent biliary drainage. Microscopic evaluation of bile was
      performed and pathologic components were classified in cholesterol microcrystals,
      bilirubinate granules, and calcium microspherolites. RESULTS: Five patients
      showed no abnormalities. In 11 patients, bilirubinate granules were found,
      cholesterol microcrystals in two, and Giardia lamblia in two. CONCLUSION:
      Bilirubinate granules are the main pathologic component of bile in patients with
      acute idiopathic pancreatitis. Cholecystectomy is the preferred therapeutic
      approach.

PMID- 9517639
TI  - Clinical and virological course of chronic hepatitis B virus infection with
      hepatitis C and D virus markers.
AB  - OBJECTIVE: Hepatitis B, C, and delta virus (HBV, HCV, HDV) share similar
      transmission routes; thus, dual or triple infections may occur and even persist
      in the same patient. However, little is known about the presentations and course
      of chronic HBV infection with HCV and HDV markers, which this study examined.
      METHODS: Antibodies against HCV (anti-HCV) and HDV (anti-HDV) were assayed as
      appropriate in patients with HBV infection. The clinical, pathological, and
      virological presentations as well as the course of the disease in patients with
      HBV/HDV/HCV triple infection markers were then reviewed. RESULTS: A total of 60
      patients, 51 men and nine women, age 19-67 yr (mean 45.9+/-1.6 yr) were
      identified. Of these 60 patients, five (8.3%) were HBeAg positive and 10 (16.7%)
      cirrhotic at entry, 30 (50%) presented with acute superinfection (HCV or HDV, or
      both) and the remaining 30 presented with chronic liver disease. On presentation,
      16 (53.3%) of the 30 patients with acute superinfection showed hepatic
      decompensation and eight (26.7%) died. In contrast, only one of the patients with
      "chronic liver disease" presented with hepatic decompensation. Of the 42 patients
      followed up for 1-15 (mean, 4.7+/-0.6) yr, 45.2% showed remission and 19% showed
      HBsAg seroclearance, whereas 12.5% of the 32 noncirrhotics developed cirrhosis
      and three of the nine cirrhotics became decompensated. At the end of follow-up,
      29 patients (69.9%) were still seropositive for HCV-RNA but only nine (22.5%)
      were seropositive for HDV-RNA and five (12.5%) were seropositive for HBV-DNA.
      CONCLUSIONS: These results suggest that infection with HBV, HCV, and HDV triple
      markers is a severe disease in acute superinfection stage but that the course is
      relatively benign, slowly progressive, and usually dominated by HCV.

PMID- 9517641
TI  - LDH to AST ratio in biliary pancreatitis--a possible indicator of pancreatic
      necrosis: preliminary results.
AB  - OBJECTIVE: Lactate dehydrogenase (LDH) has been reported to be a sensitive
      indicator of pancreatic necrosis (PN). In patients with biliary pancreatitis
      (BP), however, liver enzymes are generally elevated early in the course of the
      disease because of acute inflammatory liver cell injury caused by ampullary
      stones impacted during their transpapillary passage. Accordingly, the
      identification of PN using the initial high LDH activity as an indicator of PN in
      BP may not be accurate. In patients with ongoing PN, LDH would be expected to
      increase thereafter. We hypothesized that an elevation of the ratio of LDH to
      aspartate aminotransferase (AST) (LDH/AST) would better reflect PN in BP.
      METHODS: The plasma concentrations of the LDH/AST ratio over a 3-wk postadmission
      period were evaluated and compared with serial computed tomograpy (CT) scans of
      the abdomen in two groups of patients with BP, consisting of 5 PN patients and 17
      non-PN patients. A group of 50 healthy adults served as controls for the LDH/AST
      ratio measurement. RESULTS: On postadmission days 1 and 2, the LDH/AST ratios in
      both groups of patients were low, with no significant difference. In the PN
      patients, the LDH/AST ratio increased thereafter, reached peak values, and
      decreased. In the non-PN patients, the LDH/AST ratio increased gradually, but
      remained within the control range. In the PN patients, the LDH/AST ratios on
      postadmission days 3, 5, and 7 were significantly higher than those of the non-PN
      patients. The CT scans of the abdomen of the PN patients showed an initial
      edematous pancreas with the development of late PN. The peak values of the
      LDH/AST ratio correlated well with the extent of PN. CONCLUSION: An elevated
      LDH/AST ratio identifies patients who develop PN. The LDH/AST ratio could be used
      as an indicator of PN in BP patients.

PMID- 9517642
TI  - Placebo-controlled trial of cisapride and nizatidine in unselected patients with
      functional dyspepsia.
AB  - OBJECTIVE: Patients in most trials of pharmacotherapy for nonorganic dyspepsia
      have been groups referred selectively for endoscopy, which could have led to a
      selection bias of nonresponders, explaining the negative outcome of most
      controlled treatment trials in nonorganic dyspepsia. The aim of this study was to
      evaluate the effects of cisapride and nizatidine in patients with nonorganic
      dyspepsia who were recruited directly from primary care settings, and to evaluate
      the therapeutic implications of dyspepsia subgrouping. METHODS: A consecutive
      series of patients who consulted their general practitioner with dyspepsia were
      invited to an interview and endoscopy. Before endoscopy, symptoms were classified
      as reflux-like, dysmotility-like, ulcer-like, or unclassifiable. A total of 330
      patients with either minor or no abnormalities at endoscopy were randomized to
      double blind treatment with cisapride 10 mg t.i.d., nizatidine 300 mg at night,
      or placebo for 2 wk. RESULTS: A symptomatic response was found in 62% of patients
      on cisapride (therapeutic gain cisapride vs placebo: 0.1% [95% confidence
      interval -14% to 14%]) and in 54% of patients on nizatidine (therapeutic gain
      nizatidine vs placebo: -8% [95% confidence interval -22% to 7%]). Response to
      treatment was independent of symptom classification. CONCLUSIONS: The effects of
      a 2-wk course of cisapride or nizatidine in unselected patients with dyspepsia
      recruited from primary care were not superior to those of placebo. Symptom
      subgrouping was not predictive of response to therapy.

PMID- 9517643
TI  - Atrophic gastritis and intestinal metaplasia in Helicobacter pylori infection:
      the role of CagA status.
AB  - OBJECTIVE: Helicobacter pylori (H. pylori) is a major factor in determining the
      risk for development of gastric adenocarcinoma through the intermediate steps of
      atrophic gastritis and intestinal metaplasia. Because H. pylori infection is
      highly prevalent in asymptomatic populations and only a few people develop
      cancer, additional factors may influence the risk for development of cancer, once
      infection is established. Some factors may pertain to differences among bacterial
      strains. Because infection by H. pylori strains possessing cagA (cytotoxin
      associated gene A), a gene encoding a high-molecular-weight immunodominant
      antigen (CagA), is associated with enhanced induction of gastritis, the aim of
      our study was to evaluate potential differences in the prevalence and intensity
      of atrophy and intestinal metaplasia between CagA-positive and CagA-negative H.
      pylori-infected patients. METHODS: Eighty H. pylori-infected patients among 120
      consecutive dyspeptic patients referred for upper gastrointestinal endoscopy were
      studied. Six bioptic specimens were taken from the gastric antrum: five for
      histological examination, and one for urease test. The H. pylori status was
      determined by histology, CLO test, and serology (in a standardized ELISA) for
      serum IgG and IgA directed to H. pylori. The CagA status was determined by
      Western blotting to detect serum IgG antibodies to CagA. Gastritis was classified
      according to the Sydney System. A score from 0 to 3 was assigned to each of the
      following morphological variables: atrophy, intestinal metaplasia, and
      mononuclear and neutrophilic cell infiltration. The association between CagA
      status and histological features was assessed by means of the chi2 test for
      trend. RESULTS: Among the 80 H. pylori-infected patients 53 (66%) were CagA
      seropositive and 27 (34%) were CagA seronegative. The mean age of the two groups
      was similar. CagA-positive patients had significantly higher scores for atrophy
      (p = 0.006), intestinal metaplasia (p = 0.01), and mononuclear (p < 0.001) and
      polymorphonuclear (p = 0.002) cell infiltration than did CagA-negative patients.
      No differences in contrast, were found for H. pylori density. CONCLUSION:
      Infection with CagA-positive H. pylori strains is associated with an increased
      prevalence and intensity of antral atrophy and intestinal metaplasia, in addition
      to higher degrees of gastritis. Our results seem to suggest that the CagA status
      could be a helpful parameter to define a subgroup of H. pylori-infected patients
      at increased risk of developing gastric adenocarcinoma.

PMID- 9517644
TI  - Ranitidine bismuth citrate with clarithromycin given twice daily effectively
      eradicates Helicobacter pylori and heals duodenal ulcers.
AB  - OBJECTIVE: Ranitidine bismuth citrate (RBC) b.i.d. with clarithromycin q.i.d.
      eradicates Helicobacter pylori (H. pylori) in 82-94% of patients, and heals
      duodenal ulcers in 88-90% of patients. This double blind, placebo-controlled
      study examines the efficacy of a simpler b.i.d. treatment regimen, and examines
      the potential benefit of including a second antibiotic, metronidazole, to the
      b.i.d. treatment regimen. METHODS: A total of 648 patients with active duodenal
      ulcer received RBC 400 mg b.i.d. for 4 wk, coprescribed with clarithromycin 250
      mg q.i.d., clarithromycin 500 mg b.i.d., or clarithromycin 500 mg b.i.d. with
      metronidazole 400 mg b.i.d. for the first 2 wk of treatment. Endoscopies were
      performed prestudy, after 4 wk of treatment, and at least 4 wk posttreatment. H.
      pylori status was assessed by CLOtest, 13C-urea breath test (UBT), and histology
      prestudy, and by UBT and histology at least 4 wk posttreatment. Adverse events
      were recorded at each visit. RESULTS: All three regimens were highly effective
      and well tolerated. H. pylori eradication rates were 84-94% and duodenal ulcer
      healing rates were 92-96% (observed data). Highest H. pylori eradication and
      ulcer healing rates were achieved with RBC 400 mg b.i.d. with clarithromycin 500
      mg b.i.d. CONCLUSION: Ranitidine bismuth citrate with clarithromycin 500 mg
      b.i.d. provides an effective, simple and well tolerated regimen for the
      eradication of H. pylori and healing of duodenal ulcers.

PMID- 9517645
TI  - Primary and acquired Helicobacter pylori resistance to clarithromycin,
      metronidazole, and amoxicillin--influence on treatment outcome.
AB  - OBJECTIVE: The aim of this study was to evaluate the primary and acquired
      resistance of H. pylori against clarithromycin, metronidazole, and amoxicillin,
      and to elucidate the consequential influence on H. pylori eradication. METHODS: A
      total of 195 patients with positive H. pylori status were consecutively included.
      In 172 patients, H. pylori could be cultured for evaluation of primary antibiotic
      resistance. Fifty patients received a 2-wk dual therapy with an acid inhibitor
      and amoxicillin 2,000 mg daily (A), the other 122 patients a 1-wk modified triple
      therapy with the acid inhibitor clarithromycin 500-1,000 mg daily, and
      metronidazole 1,000-1,500 mg daily (B: n = 78), or amoxicillin 2,000 mg daily and
      metronidazole 1,000 mg daily (C: n = 44), respectively. Acid inhibition was
      conducted with pantoprazole 40 mg b.i.d. (n = 62), omeprazole 20 mg b.i.d. (n =
      50), lansoprazole 30 mg b.i.d. (n = 10), or ranitidine 150 mg t.i.d. (n = 50).
      After therapy, 36 patients remained H. pylori-positive, 20 after dual therapy (A)
      and 16 after modified triple therapy (B: n = 7, C: n = 9). In 32 of these
      patients, H. pylori could be recultured for evaluation of acquired resistance (A:
      n = 18, B: n = 7, C: n = 7). RESULTS: Primary H. pylori resistance to
      metronidazole was observed in 36 of 172 patients (21%) and to clarithromycin in
      three of 172 (2%). Acquired resistance was found in six of 14 (43%) and in two of
      seven (29%), respectively, whereas neither primary nor acquired H. pylori
      resistance to amoxicillin was noted. Patients infected with metronidazole
      resistant H. pylori strains were successfully treated in combination with
      clarithromycin (eight of nine vs 63 of 67 with sensitive strains, NS), but not
      with amoxicillin (one of eight vs 32 of 34 with sensitive strains, p < 0.0001).
      In two patients with acquired combined clarithromycin and metronidazole
      resistance, modified triple therapy failed. CONCLUSION: The value of modified
      triple therapy with amoxicillin and metronidazole is significantly limited by
      metronidazole resistance. However, metronidazole resistance does not negatively
      influence treatment outcome in modified triple therapy including clarithromycin.
      H. pylori resistance to amoxicillin still is not present.

PMID- 9517647
TI  - Helicobacter pylori infection, reflux esophagitis, and atrophic gastritis: an
      unexplored triangle.
AB  - OBJECTIVE: H. pylori causes chronic gastritis, which may progress to peptic
      ulcer, gastric atrophy, or gastric cancer. However, little is known about the
      role of H. pylori infection in reflux esophagitis and the relationship between
      reflux esophagitis and atrophic gastritis needs to be clarified. We sought to
      identify the possible interrelationships among Helicobacter pylori infection,
      reflux esophagitis, and atrophic gastritis, to signal areas in which researchers
      should consider focusing their attention. METHODS: A broad-based Medline search
      was performed to identify all related publications addressing H. pylori
      infection, atrophic gastritis, gastroesophageal reflux disease (GERD), secretion
      of gastric acid, and gastric motility published between 1966 and July 1997.
      RESULTS: Whereas some studies have shown no significant association between H.
      pylori infection and reflux esophagitis, others have observed that the prevalence
      of H. pylori infection was lower in patients with GERD, implying a protective
      role. Eradication of H. pylori leads to occurrence of reflux esophagitis in some
      cases, but the mechanisms inducing posteradication reflux esophagitis are
      unknown. H. pylori infection may lead to atrophic gastritis (and hence
      hypochlorhydia) through both bacterial and host factors, although gastric atrophy
      and subsequent intestinal metaplasia are hostile to H. pylori because of
      hypochlorhydria. Although it has been reported that long-term proton pump
      inhibitor therapy for refractory reflux esophagitis may induce or enhance the
      development of gastric atrophy in H. pylori-infected patients, this relationship
      has been disputed. CONCLUSIONS: H. pylori infection may be negatively associated
      with reflux esophagitis, but this requires confirmation. Research then needs to
      focus on whether this is explained through motility- or acid-related mechanisms.
      The potential costs of maintenance antireflux therapy may need to be taken into
      account when evaluating the cost effectiveness of anti-H. pylori therapy.

PMID- 9517648
TI  - Ascitic fluid to serum bilirubin concentration ratio for the classification of
      transudates or exudates.
AB  - OBJECTIVE: We compared the ascitic fluid to serum bilirubin ratio with three
      other ways of classifying ascitic fluid to the categories of exudate or
      transudate: the serum-ascites albumin gradient, the total protein concentration
      of the fluid, and the adaptation of Light's criteria for the detection of pleural
      fluid exudate, i.e., fluid to serum protein or LDH ratio or fluid LDH
      concentration. (Recently it has been reported that the pleural fluid to serum
      bilirubin ratio is statistically equivalent to Light's criteria.) Also, we
      evaluated whether the addition of the bilirubin ratio to the other criteria
      increases their diagnostic accuracy. METHODS: Eighty-one specimens of ascitic
      fluid from 81 different patients were obtained. They were analyzed prospectively
      by SMA12, whereas the category of the fluid was determined according to the
      clinical diagnosis. The diagnostic accuracy of each criterion alone and in
      combination with the bilirubin ratio, with reference to the contended etiology,
      were evaluated. RESULTS: The best criterion is the albumin gradient (overall
      accuracy = 0.84). The bilirubin and LDH ratio criteria had equivalent overall
      accuracy (0.815 and 0.802, respectively). The addition of the bilirubin ratio to
      any criterion did not improve its predictive or overall accuracy. CONCLUSIONS:
      Ascitic fluid to serum bilirubin ratio is an additional marker for the
      distinction of transudate from exudate. A ratio > 0.6 has a statistically
      significant association with exudate.

PMID- 9517646
TI  - A four-day low dose triple therapy regimen for the treatment of Helicobacter
      pylori infection.
AB  - OBJECTIVE: The current guidelines recommend 1-wk triple therapy regimens for
      eradicating H. pylori infection. Until now, shorter regimens have scarcely been
      investigated. Azithromycin is a new generation macrolide antibiotic with unusual
      and favorable pharmacokinetics, and seems to be a very promising agent for
      innovative anti-H. pylori regimens. We assessed the efficacy and tolerability of
      a new 4-day low dose triple therapy in comparison with a well established 1-wk
      triple therapy in the treatment of Helicobacter pylori infection. METHODS: One
      hundred-sixty consecutive patients with biopsy-proven H. pylori infection were
      randomized to receive lansoprazole 30 mg b.i.d. on days 1-4, azithromycin 500 mg
      u.i.d. on days 2-4, and tinidazole 2000 mg u.i.d. on day 3 (LAT group), or 7 days
      of triple therapy of omeprazole 20 mg u.i.d., clarithromycin 250 mg b.i.d., and
      tinidazole 500 mg b.i.d. (OCT group). Patients with gastric or duodenal active
      ulcer received proton pump inhibitors for an additional 4 wk. H. pylori
      eradication was defined as negative of both rapid urease test and histology on
      biopsies taken from the gastric body and antrum at least 1 month after the end of
      treatment. RESULTS: Seven patients in the LAT group and four in the OCT group
      were lost to follow-up. No significant difference in either efficacy or
      tolerability was observed between the two regimens. Active ulcers healed in 97.8%
      of cases with LAT and in 100% of cases with OCT. The eradication rate was 80.8%
      in the LAT group and 85.5% in the OCT group, considering the per-protocol
      results, and 73.3% and 81.2%, respectively, considering the intention-to-treat
      results. Side effects occurred in one LAzT patient and in two OCT patients; they
      were mild and did not interfere with compliance. CONCLUSION: The new proposed
      ultrashort triple therapy, including lansoprazole, low dose azithromycin for 3
      days, and a single dose of tinidazole, appears to be a very effective anti-H.
      pylori regimen, a simpler, cheaper, well-tolerated, and equally effective
      alternative to 1-wk triple therapy.

PMID- 9517649
TI  - Direct determination of colonic nitric oxide level--a sensitive marker of disease
      activity in ulcerative colitis.
AB  - OBJECTIVE: In active ulcerative colitis, colonic nitric oxide (NO) generation is
      enhanced and probably has an important role in its pathogenesis. We tested the
      reliability of an NO electrode in monitoring colonic NO levels in ulcerative
      colitis patients and control subjects and its possible usage as a marker of
      disease activity. METHODS: Colonic NO level was determined by the NO detection
      system model NO-501 (InterMedical, Nagoya, Japan). The working electrode was
      inserted into a 7-mm diameter polyvinyl tube and introduced at a distance 6 cm
      from the anus. In each subject sigmoidoscopy was performed and mucosal biopsies
      were obtained. NO synthase (NOS) activity was determined by monitoring the
      conversion of 3H-arginine to citrulline. RESULTS: Colonic NO level is
      significantly increased in patients with active ulcerative or Crohn's colitis-
      more than 2-fold higher than in control subjects. There was good correlation
      between colonic NO level and NOS activity and the clinical and endoscopic indices
      of disease activity. CONCLUSION: Direct determination of colonic NO level is
      convenient, and reliable, and may help to monitor disease activity in ulcerative
      colitis.

PMID- 9517650
TI  - Randomized prospective trial of early versus delayed feeding after percutaneous
      endoscopic gastrostomy placement.
AB  - OBJECTIVE: By convention, most clinicians delay feeding through the gastrostomy
      tube until 24 h after placement. However, evidence is lacking to support the
      rationale for such a delay in PEG use. This randomized, prospective study was
      designed to assess the safety of early feeding after PEG placement. METHODS: One
      hundred-twelve patients referred for PEG were randomized to begin tube feedings
      at 4 h (group A) or at 24 h (group B) after placement. All patients received
      prophylactic antibiotics. Full-strength Isocal was administered with the
      following schedule: day 1, 100 ml every 4 h for six feedings; day 2, 200 ml every
      4 h for six feedings. Immediately before each scheduled feeding, gastric residual
      volume was recorded and the next feeding was withheld if the residual volume was
      > 50 percent (gastric retention). Patients were evaluated on day 1, day 2, day 7,
      and day 30 for major and minor complications. RESULTS: The two groups were
      similar with regard to age, gender, baseline nutritional status, and indications
      for PEG placement. On the first day of feeding, 14 of 57 patients (25%) in group
      A, but only five of 55 patients (9%) in group B, had evidence of gastric
      retention, p = 0.029. The proportion of patients with high gastric residual
      volumes was not significantly different on day two. In group B, one death
      occurred because of aspiration of gastric contents on day 2. All other
      complications were minor and did not differ significantly between the two groups.
      CONCLUSIONS: Early initiation of PEG feedings is safe, well tolerated, and
      reduces cost by decreasing hospital stay.

PMID- 9517651
TI  - A retrospective analysis of 1570 appendiceal carcinoids.
AB  - OBJECTIVE: Information about the management and outcome of appendiceal carcinoids
      is sparse, because few series comprise more than 100 cases. In this study we have
      analyzed the epidemiology of 1570 appendiceal carcinoids, to compare outcome with
      other gastrointestinal carcinoid tumors. METHODS: We evaluated 1570 appendiceal
      carcinoids in a series of 8305 carcinoid tumors from the SEER, the End Results
      Group, and the Third National Cancer Survey programs of the National Cancer
      Institute over the time period 1950-1991. RESULTS: Appendiceal carcinoids
      comprised 18.9% of all carcinoid tumors and exhibited a marked female
      predominance (M/F ratio: 0.47). Age-adjusted incidence rates were 1.7-fold higher
      in women compared to men. Appendiceal carcinoids present earlier (average age:
      42.2 yr) than other gastrointestinal carcinoids (62.9 yr) or noncarcinoid
      appendiceal tumors (61.9 yr). At the time of diagnosis 35.4% were nonlocalized.
      The overall 5-yr survival for localized lesions was 94%, for regional invasion
      84.6%, and for distant metastases 33.7%. The 5-yr survival of appendiceal
      carcinoids (85.9%) was the highest among all types of carcinoid tumors. In 14.6%
      noncarcinoid tumors at other sites were also evident. CONCLUSION: The high
      relative incidence of carcinoid tumors in the appendix is still poorly
      understood. The good overall 5-yr survival rates of appendiceal carcinoids as
      opposed to other carcinoids represents either a different biological behavior,
      earlier diagnosis, or expeditious management (appendectomy). However, the
      increased likelihood of coexisting neoplasms and the not uncommon presentation of
      metastatic disease should warrant careful evaluation and postoperative follow-up
      of such lesions.

PMID- 9517652
TI  - Beneficial hemodynamic effects of dipyridamole on portal circulation in
      cirrhosis.
AB  - OBJECTIVE: Dipyridamole is a vasodilator that inhibits the cellular uptake of
      adenosine, which physiologically reduces the resistance to hepatic arterial flow
      inside the liver. This study aims at assessing the acute effect of dipyridamole
      on functional liver plasma flow (measured as the extrarenal sorbitol clearance)
      and on the Doppler US Congestion Index of the portal vein (the ratio between the
      cross-sectional area of this vein and the mean velocity of portal flow), which
      correlates with the severity of portal hypertension. METHODS: We have determined
      the extrarenal sorbitol clearance (14 cases) and the Congestion Index (seven
      cases) before and at 30, 60, and 90 min after the oral administration of 25 mg
      dipyridamole in patients with liver cirrhosis. We also measured the effect of
      dipyridamole on functional liver plasma flow in six healthy subjects. RESULTS:
      Dipyridamole increased the extrarenal sorbitol clearance in controls (+17%, p <
      0.01) and in cirrhotic patients (+15%, p < 0.01). The drug decreased the portal
      Congestion Index in all patients, averaging -24% (p < 0.05) 90 min after its oral
      administration. CONCLUSIONS: This result was due both to a mean decrease of the
      portal sectional area and to a mean increase in portal flow velocity. In
      conclusion, these data suggest that dipyridamole should decrease the vascular
      resistance to portal flow in cirrhosis; this effect may be mediated by an
      adenosine-dependent vasodilation in the intrahepatic site or along the
      portosystemic collaterals.

PMID- 9517653
TI  - Abnormal duodenal bile composition in patients with acalculous chronic
      cholecystitis.
AB  - OBJECTIVE: Our goal was to characterize biliary lipid composition in patients
      with the syndrome of chronic biliary pain, absence of gallstones, and
      inflammation of the gallbladder mucosa (acalculous chronic cholecystitis).
      METHODS: Duodenal bile, obtained from 27 patients with a history of right upper
      quadrant pain and with negative imaging studies of the biliary tract, was
      analyzed enzymatically for bile acids, phospholipids, and cholesterol. Fifteen
      patients were found to have inflammation and/or fibrosis of the gallbladder at
      cholecystectomy. RESULTS: The 15 patients with abnormal gallbladder histology had
      more dilute duodenal bile, as indicated by a low bile acid concentration and a
      lower proportion of phospholipids (p < 0.01) when values were compared with those
      of duodenal bile samples from postmenopausal women without gallbladder disease or
      from radiolucent gallstone subjects participating in the National Cooperative
      Gallstone Study. Cholecystectomy relieved pain in 9 of 14 patients. CONCLUSIONS:
      Some patients with acalculous chronic cholecystitis have duodenal bile samples
      characterized by a decreased bile acid concentration and a decreased proportion
      of biliary phospholipids. The low biliary bile acid concentration may result from
      impaired gallbladder contraction and/or secretion by the biliary tract
      epithelium. The low proportion of phospholipid may result from posthepatic
      hydrolysis of luminal phosphatidylcholine followed by absorption of the
      hydrolysis products. The latter process could be caused by and/or contribute to
      mucosal inflammation and would also elevate the cholesterol saturation of bile,
      increasing the risk for cholesterol gallstone formation.

PMID- 9517655
TI  - Carcinoma of the stomach with hyperkeratosis palmaris et plantaris and acanthosis
      of the esophagus.
AB  - A 59-yr-old man with carcinoma of the stomach, concurrent acquired hyperkeratosis
      (tylosis) of the palms and soles, and acanthosis of the esophageal mucosa is
      reported. He presented the tylosis and esophageal lesions when the carcinoma was
      evident. Resection of the stomach resulted in diminution of the skin and
      esophageal lesions. The association of sporadic tylosis and carcinoma of the
      stomach is extremely rare. This is the first case report documenting the
      association of gastric cancer, tylosis, and acanthosis of the esophageal mucosa.

PMID- 9517654
TI  - Clinical outcome following treatment of refractory inflammatory and fistulizing
      Crohn's disease with intravenous cyclosporine.
AB  - OBJECTIVE: To determine outcome following treatment of refractory Crohn's disease
      with intravenous (i.v.) cyclosporine (CYA). METHODS: The medical records of 18
      patients with refractory Crohn's disease treated with i.v. CYA were reviewed.
      Nine patients had refractory inflammatory Crohn's disease and nine patients had
      complex fistulizing Crohn's disease. All patients were initially treated with
      i.v. CYA (4 mg/kg/day). Patients who responded were converted to standard oral
      CYA. Patient outcomes were classified as complete response, partial response, or
      nonresponse. RESULTS: Four of nine patients with severe inflammatory Crohn's
      disease and seven of nine patients with fistulizing Crohn's disease had a partial
      response to i.v. CYA. Four of four responding patients in the inflammatory group
      and four of six responding patients in the fistulizing group (plus one initial
      nonresponder) maintained or improved their response during oral CYA therapy.
      After discontinuing oral CYA, all four patients in the inflammatory group and
      five of seven patients in the fistulizing group relapsed despite 1-17 wk of
      concomitant treatment with azathioprine or 6-mercaptopurine (AZA/6MP). Two
      patients who received overlapping CYA and AZA/6MP for 17 and 23 wk maintained
      long-term responses. CYA toxicity was minimal: reversible nephrotoxicity (n = 2),
      headache (n = 2), oral candidiasis (n = 1), paresthesia (n = 2). CONCLUSIONS:
      I.v. CYA appears to benefit both refractory inflammatory and fistulizing Crohn's
      disease. Most patients who respond to i.v. CYA will maintain their response
      during oral CYA therapy. However, the majority of these patients relapse when
      oral CYA is discontinued, probably because of inadequate duration of overlap with
      the slow acting maintenance drugs, AZA/6MP.

PMID- 9517656
TI  - Acute ileal diverticulitis.
AB  - Four cases of acute ileal diverticulitis are presented wherein early diagnosis
      helped avoid emergent surgery. All patients did well initially with conservative
      medical management. Acute ileal diverticulitis, although uncommon, should be
      suspected when the clinical presentation indicates an inflammatory condition of
      the lower right abdomen. Surgery, when required for recurrent disease, can be
      reserved for the interval between acute episodes.

PMID- 9517657
TI  - Transjugular intrahepatic portosystemic shunt: a successful treatment for
      hepatopulmonary syndrome.
AB  - Hepatopulmonary syndrome is a well described complication of chronic liver
      disease. Though uncommon, it carries a high morbidity and mortality. The
      pathogenesis of the syndrome has not been clearly defined. Portal hypertension
      seems to play a crucial role in the pathogenesis of the syndrome, probably by
      enhancing nitric oxide production. As yet, no pharmacological therapy has been
      proven effective. Many reports of successful reversal of the syndrome after liver
      transplantation have been published. We report a patient with hepatopulmonary
      syndrome who showed a significant and durable (4 months') improvement in his
      symptoms, arterial oxygenation, and intrapulmonary shunts, as calculated by
      radionuclide studies after transjugular intrahepatic portosystemic shunt
      placement. Transjugular intrahepatic portosystemic shunt may represent a durable
      treatment option for patients with hepatopulmonary syndrome.

PMID- 9517658
TI  - Terbinafine hepatotoxicity: case report and review of the literature.
AB  - We report a patient who developed significant liver dysfunction following therapy
      with terbinafine. At the end of a 3 1/2-wk course of terbinafine, he developed
      progressive jaundice and pruritus. His serum bilirubin peaked at 30.9 mg/dl 3 wk
      after discontinuing terbinafine. A liver biopsy revealed mild to moderate mixed
      cellular infiltrate in the portal tracts, and hepatocellular and canicular
      cholestasis. His liver tests normalized 100 days after stopping terbinafine.

PMID- 9517659
TI  - Sialadenoma papilliferum of the esophagus.
AB  - Sialadenoma papilliferum is an extremely rare benign tumor of the esophagus. We
      report a 70-yr-old woman who was first thought to have adenocarcinoma in the
      distal esophagus. Transhiatal esophagectomy and left colon interposition were
      performed. The pathological diagnosis of sialadenoma papilliferum of the
      esophagus arising in the submucosal gland ducts was confirmed after surgery.

PMID- 9517660
TI  - Cutaneous necrosis associated with interferon alpha-2b.
AB  - Cutaneous necrosis may occur as a complication of treatment with interferon. Here
      we report the first case of cutaneous necrosis developing in a patient receiving
      interferon alpha-2b for the treatment of chronic hepatitis C viral infection. The
      patient developed two necrotic lesions while receiving high doses of interferon.
      We suggest that discontinuation of treatment may be necessary to permit healing
      of such lesions. Although the exact mechanism involved in cutaneous necrosis
      remains unknown, our observations support earlier findings suggesting that
      intraarterial injection may be a factor.

PMID- 9517661
TI  - Esophagopericardial fistula arising from Barrett's esophagus.
AB  - Esophagopericardial fistula is a rare complication of numerous benign, malignant,
      and traumatic conditions of the esophagus. Approximately 100 cases of fistulae
      between the esophagus and heart have been reported. We describe the second
      reported case of an esophagopericardial fistula secondary to a benign esophageal
      ulcer within Barrett's mucosa without prior surgery. The radiologic, endoscopic,
      and surgical management of this case are discussed.

PMID- 9517662
TI  - Hepatitis-associated aplastic anemia and acute parvovirus B19 infection: a report
      of two cases and a review of the literature.
AB  - Hepatitis-associated aplastic anemia is rare in general, but occurs in up to 28%
      of patients receiving liver transplantation for fulminant non-A, non-B hepatitis.
      Cases are commonly young men with mild hepatitis but severe aplastic anemia.
      Although cases have been reported in association with hepatitis A, B, and C, most
      appear to be due to a non-A-B-C virus. We report two cases of acute hepatitis
      subsequently complicated by marrow hypoplasia in patients with acute parvovirus
      B19 infection. Hepatic manifestations of parvovirus B19 infection range from
      liver chemistry abnormalities to fulminant hepatic failure and aplastic anemia.
      Our cases demonstrate a less severe form of hepatitis-associated aplastic anemia,
      and together with other data, suggest that parvovirus B19 is at least one cause
      of hepatitis-associated aplastic anemia, and may be a heretofore underrecognized
      hepatotrophic virus.

PMID- 9517663
TI  - Severe symptomatic sinus bradycardia associated with mesalamine use.
AB  - A 29-yr-old white woman was hospitalized with bloody diarrhea secondary to
      ulcerative colitis. Within 24 h of receiving intravenous steroids, loperamide,
      and mesalamine, she developed symptomatic hypotension, severe sinus bradycardia,
      sinus pauses, and junctional escape beats. The hypotension and sinus bradycardia
      resolved after discontinuing mesalamine. She had a family history of conduction
      tissue disease but her exercise ECG and Holter studies were normal. She was
      rehospitalized 6 wk later with an exacerbation of ulcerative colitis and, within
      8 h of receiving mesalamine, developed hypotension and severe sinus bradycardia,
      which resolved after stopping mesalamine. Thus mesalamine should be used with
      caution, especially in patients predisposed to cardiac conduction tissue disease.

PMID- 9517664
TI  - Liver failure caused by hepatic angiodysplasia in hereditary hemorrhagic
      telangiectasia.
AB  - Hereditary hemorrhagic telangiectasia is a systemic vascular disease with
      autosomal dominant inheritance that results in telangiectasia, arteriovenous
      malformations, and hemangiomas. The liver is one of the organs commonly affected
      in hereditary hemorrhagic telangiectasia, and hepatic lesions consist of
      angiodysplasia and fibrosis. A patient with hereditary hemorrhagic telangiectasia
      and significant impairment of synthetic liver function is reported. Dynamic
      computed tomography revealed marked enlargement of the common hepatic and
      intrahepatic arteries, heterogeneous parenchymography, and early opacification of
      the hepatic veins consistent with telangiectasias and arteriovenous shunting.
      Overall, the liver was predominantly occupied by vascular structures and scarce
      residual hepatic parenchyma. Other causes of liver dysfunction, such as viral
      hepatitis and alcohol abuse, were excluded. In general, hepatic fibrovascular
      dysplasia seen in hereditary hemorrhagic telangiectasia usually results in only
      mild liver dysfunction; however, this case shows that hepatic involvement may
      rarely result in hepatic failure.

PMID- 9517665
TI  - Extensive hepatic infarction caused by thrombosis of right portal vein branches
      and arterial vasospasm in HELLP syndrome associated with homozygous factor V
      Leiden.

PMID- 9517666
TI  - American Cancer Society guidelines--are we truly improving all aspects of
      effectiveness?

PMID- 9517667
TI  - Early ERCP in biliary pancreatitis: a macho mistake?

PMID- 9517668
TI  - Achalasia management: difficult no matter how you slice it!

PMID- 9517669
TI  - Acarbose-induced acute hepatitis.

PMID- 9517670
TI  - Idiopathic ulcerative colitis in patients with primary sclerosing colitis
      undergoing orthotopic liver transplantation (OLT)

PMID- 9517671
TI  - The vacA genotypes in 167 isolates from Japanese patients with either peptic
      ulcers or non-ulcer dyspepsia.

PMID- 9517672
TI  - Effect of transjugular intrahepatic portosystemic shunt (TIPS) on glycemic
      control in cirrhotic patients with diabetes mellitus.

PMID- 9517673
TI  - Pseudomonas aeruginosa cholangitis in a HIV patient.

PMID- 9517674
TI  - Research and the Internet.

PMID- 9517675
TI  - Esophageal metastases of renal carcinoma.

PMID- 9517676
TI  - Re: testing for Helicobacter pylori infection after antibiotic treatment.

PMID- 9517677
TI  - Re: management of post-cholecystectomy biliary leaks during the laparoscopic era.

PMID- 9517679
TI  - Re: Intrahepatic metastasis in hepatocellular carcinoma: evidence for spread via
      the portal vein as an efferent vessel.

PMID- 9517678
TI  - Tuberculous pancreatic abscess presenting as acute pancreatitis in a renal
      transplant recipient.

PMID- 9517680
TI  - Response of serum indicators of myocardial infarction following exercise-induced
      muscle injury.
AB  - The purpose of this investigation was to determine the response of three
      parameters used in the assessment of acute myocardial infarction (AMI) after a
      single bout of eccentric exercise designed to elicit skeletal muscle injury.
      Total creatine kinase (CK), CK-MB isoenzyme (CK-MB), and the leukocyte
      differential were determined after a 20-minute bench-stepping exercise in 21 men
      ranging in age from 30 to 45 years. Comparison of several criteria showed that
      the use of CK-MB or the relative lymphocyte percentage alone resulted in 11% and
      1.8%, respectively, of data collection points exceeding cutoff values suggestive
      of AMI. However, the use of both parameters in combination completely eliminated
      false-positive results with no data collection points meeting the criterion. It
      is thus suggested that CK-MB activity in conjunction with the relative lymphocyte
      percentage may not only provide incremental value in the detection of AMI but
      also reduce the incidence of misdiagnosis associated with exercise.

PMID- 9517681
TI  - Prehospital gastrointestinal decontamination of toxic ingestions: a missed
      opportunity.
AB  - The purpose of this study was to determine if emergency medical services (EMS)
      providers routinely initiate field gastrointestinal decontamination of adult drug
      overdose patients transported to the emergency department (ED). A retrospective
      prehospital chart review was performed on adult patients identified as drug
      overdose who were transported by EMS. ED charts on patients transported to a
      university hospital were reviewed for follow-up data. Prehospital care records
      showed that gastrointestinal decontamination was initiated in only 6 of 361 (2%)
      patients, all of whom received ipecac. No patient received activated charcoal.
      The median transport time was 25 minutes (range, 5 to 66 minutes). Follow-up data
      on patients transported to the university hospital revealed that 30 of 43 (70%)
      patients who might have been suitable candidates for prehospital activated
      charcoal actually received activated charcoal in the ED. Median time to activated
      charcoal in the ED was 82 minutes (range, 32 to 329 min). Use of activated
      charcoal in the field appears to be deferred despite its known loss of efficacy
      over time. The failure to start activated charcoal in the field contributes to
      the delay in initiating activated charcoal therapy.

PMID- 9517682
TI  - Effect of temperature and pH adjustment of bupivacaine for intradermal
      anesthesia.
AB  - To determine the effects of warming and buffering of 0.5% bupivacaine on the pain
      associated with intradermal injection and the time of onset of anesthesia, 40
      adult volunteers were entered into a randomized, double-blind study conducted at
      a community teaching hospital. The three-part study compared room temperature (20
      degrees) bupivacaine buffered to a pH of 7.1 with the following solutions:
      buffered bupivacaine warmed to 37 degrees C, unbuffered bupivacaine at room
      temperature, and unbuffered bupivacaine warmed to 37 degrees C. The same
      crossover protocol was followed for each part of the study. Subjects received 0.5
      mL intradermal injections through 27-gauge needles over 30 seconds, one study
      solution in each forearm. Immediately after each injection, pain was assessed
      using a 100-mm visual analog pain scale. The time of onset of anesthesia (loss of
      intradermal sensation to pinprick) was measured by stopwatch. The mean perceived
      pain score for the warm buffered bupivacaine (51 mm) was significantly lower than
      for the room temperature buffered solution (63 mm, P = .003). Similarly, there
      was a statistical difference between the room temperature buffered and unbuffered
      solutions (65 v 78 mm, P < .001). The differences in mean pain scores for the
      room temperature buffered bupivacaine, compared with the other three solutions,
      suggest that warming and buffering have an additive effect. In this model, the
      latency of action of bupivacaine was not affected by alkalinization. However,
      warming bupivacaine to 37 degrees C reduced the time of onset to intradermal
      anesthesia by 12.1 seconds (95% confidence interval, 0.6 to 23.6). These results
      suggest that warming is more effective than buffering to reduce the pain of
      infiltration of bupivacaine and the time of onset of intradermal anesthesia.

PMID- 9517683
TI  - Prilocaine-phenylephrine and bupivacaine-phenylephrine topical anesthetics
      compared with tetracaine-adrenaline-cocaine during repair of lacerations.
AB  - The effectiveness of two new topical anesthetics that do not contain cocaine
      (prilocaine-phenylephrine and bupivacaine-phenylephrine) was compared with that
      of tetracaine-adrenaline-cocaine (TAC) during laceration repair in children. This
      study was a prospective, randomized, double-blind trial conducted in the
      emergency department of a large children's hospital. Participants were 180
      children 1 year of age or older with a laceration 5 cm or less in length that
      required suturing. Pain felt during suturing was scored by suture technicians,
      research assistants, parents, and patients 5 years of age and older using a
      visual analogue scale (VAS). There was no statistical difference demonstrated
      between the effectiveness of prilocaine-phenylephrine and that of TAC for any of
      the observer groups. A statistically significant difference was seen among
      anesthetics when comparing VAS scores of research assistants (P = .002), suture
      technicians (P = .006), and parents (P = .03), but not when comparing VAS ratings
      of patients (P = .07). Based on Tukey's post hoc test, these statistically
      significant differences were between TAC and bupivacaine-phenylephrine. When
      power analyses were performed using alpha = 0.05 and beta = 0.20, it was possible
      to detect a difference of 1.3 VAS units for each rater group. In conclusion, this
      study demonstrated the effectiveness and safety of prilocaine-phenylephrine and
      bupivacaine-phenylephrine. Prilocaine-phenylephrine statistically outperformed
      bupivacaine-phenylephrine and offers an effective alternative to TAC during
      laceration repair in children.

PMID- 9517684
TI  - Intubation success rates improve for an air medical program after implementing
      the use of neuromuscular blocking agents.
AB  - To determine whether the success rate for endotracheal intubation improves after
      implementing the use of neuromuscular blocking (NMB) agents in an air medical
      program, this retrospective study analyzed all patients requiring endotracheal
      intubation at two air medical programs (nurse/paramedic crews) over a 5-year
      period. Air medical program A, the control group, had employed NMB agents
      throughout the entire study period. Air medical program B, which did not use NMB
      agents from July 1, 1989 through June 30, 1992, implemented their use starting
      July 1, 1992. For program A, the overall intubation success rate was 93.5% (202
      successful intubations in 216 patients) and the successful intubations/total
      attempts ratio was 0.67 (202 of 301). For program B, the overall intubation
      success rate improved from 66.7% (46 successful intubations in 69 patients)
      before NMB agent use to 90.5% (57 in 63) after NMB agent use (P = .001). The
      successful intubations/total attempts ratio increased from 0.36 (51 of 141) prior
      to NMB agent use to 0.48 (63 of 132) after NMB agent use (P = NS). In comparing
      the 92 patients who did not receive NMB agents to the 40 patients who did, the
      intubation success rate increased from 69.6% (64 of 92) to 97.5% (39 of 40) (P <
      .001) and the successful intubation/total attempts ratio increased from 0.36 (73
      of 202) to 0.58 (41 of 71) (P = .007). With the use of NMB agents, program B's
      overall intubation success rate increased significantly, matching the results of
      program A.

PMID- 9517685
TI  - Nonbattering presentations to the ED of women in physically abusive
      relationships.
AB  - To determine which diagnoses in the emergency department (ED), apart from
      battering injuries, were more common among women who were living in physically
      abusive relationships than among women who were not, a study was conducted in 10
      hospital-based EDs in two cities serving inner city, urban, and suburban
      populations. A total of 9,057 women between the ages of 19 and 65 years
      presenting to the EDs were eligible for the study. Medical records were reviewed,
      and a written questionnaire was used. The questionnaire was completed by 4,501
      (73% of those asked, 59% of those eligible, and 50% of those presenting). Two
      hundred sixty-six (5.9%) were currently in a physically abusive relationship but
      not in the ED for battering injuries, and 3,969 (88.2%) were not currently in a
      physically abusive relationship. An additional 266 (5.9%) were positive,
      probable, or suggestive for battering injuries and excluded from diagnosis
      comparisons. Women in physically abusive relationships were more likely to be
      diagnosed with urinary tract infections, neck pain, vaginitis, foot wound,
      suicide attempt, and finger fracture. However, these represented only 19.8% of
      diagnoses in this group. The use of this knowledge alone to predict the presence
      of intimate violence in individual patients in the ED will not identify the
      majority of women at risk. These results suggest the use of routine inquiry for
      abuse in all women.

PMID- 9517686
TI  - Comparative study of methods of measuring acute pain intensity in an ED.
AB  - The best one-dimensional method for routine self-assessment of acute pain
      intensity in a hospital emergency department is unknown. In this study, an 11
      point numerical rating scale (NRS), a simple verbal rating scale describing five
      pain states (VRS), and a visual analogue scale (VAS) were presented successively
      on admission to 290 patients with acute pain (200 with and 90 without trauma).
      VAS and NRS were closely correlated for both traumatic (r = .795) and
      nontraumatic pain (r = .911). The VAS could not be used with 19.5% of patients
      with trauma and the VRS with 11% of patients without trauma, whereas the NRS
      could be used with 96% of all patients. The NRS proved more reliable for patients
      with trauma, giving equivalent results to those with the VAS for patients without
      trauma. These two scales showed better discriminant power for all patients. Thus,
      the NRS would appear to be the means for self-evaluation of acute pain intensity
      in an emergency department.

PMID- 9517687
TI  - Disease surveillance in the ED: factors leading to the underreporting of
      gonorrhea.
AB  - Emergency departments (EDs) are potentially important surveillance sites. This
      study assessed reporting completeness for gonorrhea by hospital and gender and
      explored reasons for underreporting. A retrospective review was conducted of ED
      charts from three hospitals for 2 months. Potential gonorrhea cases were
      identified by history, physical examination, testing, treatment, and diagnostic
      practices. Cases were divided into those tested only, those treated with or
      without testing, and those with positive tests. Reporting completeness was
      assessed for each. Of 936 cases included, 29.0% were tested without treatment and
      71% received treatment. One third of treated patients were not tested, and none
      of these were reported. Two EDs reported cases themselves and reported 75.9% of
      confirmed cases. There were significant differences in testing and reporting
      between hospitals and genders. Underreporting of suspected and confirmed
      gonorrhea cases was common from these EDs. A major cause was physicians treating
      without testing for confirmation.

PMID- 9517688
TI  - Repeated ambulance use by patients with acute alcohol intoxication, seizure
      disorder, and respiratory illness.
AB  - Three chronic conditions were examined--acute alcohol intoxication, seizure
      disorder, and respiratory illness--to quantify the extent of repetitive emergency
      medical services (EMS) use in a defined population. Urban EMS system ambulance
      data from 1992 to 1994 were analyzed for the three designated conditions with
      respect to transports by condition and individual patient. Analysis by chi2 was
      used for comparing proportions. Analysis of variance after square root
      transformation was used to evaluate differences among means. The total number of
      transports analyzed was 15,541: 7,488 for acute alcohol intoxication, 4,670 for
      respiratory illness, and 3,383 for seizure disorder. These transports involved
      8,692 patients who were transported at least once for one of the three designated
      conditions. The mean number of transports for alcohol was 1.96 (95% confidence
      intervals [CI]: 1.92, 2.01), seizure 1.32 (95% CI: 1.27, 1.36), and respiratory
      1.18 (95% CI: 1.15, 1.21). Of 369 patients transported five or more times during
      the study period, 260 (70.5%) were for alcohol, 56 (15.2%) for seizure, and 53
      (14.4%) for respiratory complaints. This group comprised only 4.3% of patients,
      but 28.4% of all transports. Acute alcohol intoxication resulted in more
      repetitive ambulance transports than either seizure disorder or respiratory
      illness. A small number of patients were responsible for a large number of
      transports. Focused intervention for patients with high ambulance transport
      deserves further study.

PMID- 9517690
TI  - Significance of the initial spun hematocrit in trauma patients.
AB  - This study was designed to determine whether the initial spun hematocrit (HCT)
      value correlated with blood loss requiring operative intervention (OR). A spun
      HCT was performed on the first available blood sample from 524 admitted patients
      12 years of age or older with traumatic injuries (86% blunt, 14% penetrating).
      Patients in the OR (n = 66) group had a lower mean HCT (35 v 41, P < .001) when
      compared with the non-OR group. The 81 patients with an HCT of < or = 35 required
      OR more frequently (41% v 7%, P < .001). An HCT of < or = 35 had a sensitivity of
      50%, specificity of 90%, positive predictive value of 41%, and negative
      predictive value of 93% for identifying the OR group. The effect of hemodilution
      from intravenous fluid is difficult to assess in a retrospective clinical study.

PMID- 9517689
TI  - Injuries distracting from intraabdominal injuries after blunt trauma.
AB  - While most conscious patients with severe intraabdominal injuries (IAI) will
      usually present with either abdominal pain or tenderness, there is a small group
      of awake and alert patients in whom the physical examination will be falsely
      negative because of the presence of associated extraabdominal ("distracting")
      injuries. We sought to define the types of extraabdominal injuries that could
      lead to a false negative physical examination for potentially severe IAI in adult
      victims of blunt trauma. This study was prospectively performed on consecutive
      blunt trauma patients over a 14-month period in our level I trauma center.
      Inclusion criteria were as follows: (1) Glasgow Coma Scale score of 15; (2) age
      18 years or older; and (3) computed tomography (CT) of the abdomen or diagnostic
      peritoneal lavage (DPL) performed regardless of initial physical examination
      findings. Patients were questioned specifically about the presence of abdominal
      pain and the initial abdominal examination was documented in addition to other
      extraabdominal injuries. Abdominal injuries were considered to be present based
      upon either abdominal CT findings or a positive DPL. Patients with and without
      abdominal pain or tenderness were compared for the presence of IAI. A total of
      350 patients were enrolled. There were 142 patients with neither abdominal pain
      nor tenderness (group 1) and 208 patients with either or both (group 2). Ten of
      the 142 patients (7.0%) in group 1 had IAI compared with 44 of the 208 patients
      (21.2%) in group 2 (P = .0003). Presence of pain and/or tenderness had a
      sensitivity of 82%, a specificity of 45%, a positive predictive value of 21%, and
      negative predictive value of 93%. All 10 patients in group 1, and 36 of the 44
      group 2 patients, had associated extraabdominal injuries. Although the presence
      of abdominal pain or tenderness was associated with a significantly higher
      incidence of IAI, the lack of these findings did not preclude IAI.

PMID- 9517691
TI  - Axillary artery injuries after proximal fracture of the humerus.
AB  - Although axillary artery injury occurs frequently with dislocations of the
      shoulder and fractures of the clavicle, it is rarely associated with fractures of
      the proximal humerus. If the axillary artery is damaged, prompt recognition and
      treatment are necessary to salvage the involved extremity.

PMID- 9517692
TI  - Diagnosis and follow-up of Chlamydia trachomatis infections in the ED.
AB  - The purpose of this study was to determine the impact on patient care and the
      cost effectiveness of testing for chlamydial infection in the emergency
      department. All patients tested for chlamydial infection in three emergency
      departments between October 1, 1993 and January 31, 1994 were retrospectively
      reviewed for charges and adequacy of therapy. In one hospital, the effectiveness
      of a call-back system to enhance proper therapy of inadequately treated patients
      was evaluated. Of 2,416 test results, 249 were positive, and 197 of these charts
      were available for review. All 16 male patients were treated appropriately at the
      initial visit; 105 of 181 female patients were inadequately treated at the
      initial visit. The charge to identify each patient inadequately treated was
      $981.22 ($103,000 for 105). Of the 28 inadequately treated patients receiving a
      follow-up call, 20 sought treatment. The high cost of testing patients cannot be
      justified without an adequate surveillance system to enhance proper follow-up
      treatment.

PMID- 9517693
TI  - Reduction of "callbacks" to the ED due to discrepancies in plain radiograph
      interpretation.
AB  - Retrospective and prospective chart review was conducted to study patient
      callbacks to the emergency department (ED) based on plain radiograph
      interpretation discrepancies between radiologists and emergency physicians before
      and after a continuous quality improvement (CQI) intervention. Patients who were
      called back to the ED because of radiograph interpretation discrepancies were
      retrospectively studied. These results were reviewed by a CQI team, which
      recommended greater communication and consultation. A prospective study was then
      performed. Before quality intervention, 0.7% of the patients were recalled; 0.4%
      required recall after quality assurance, a reduction of 42.9% (P = .0001).
      Emergency physicians in this study had a low percentage of patient recall due to
      discrepancies in radiologic interpretation. CQI further reduced this percentage.
      The proficiency of emergency physicians interpreting radiographs validates the
      current practice of emergency physicians rendering treatment based on their
      interpretations and supports the notion of emergency physicians billing for this
      service.

PMID- 9517694
TI  - Emergency department presentation of an unusual pleural effusion.
AB  - Pleural effusion as a manifestation of malignancy is commonly encountered in
      clinical practice; most are transudates or exudates of endogenous body fluids. We
      report a case of pleural effusion that is directly related to the inadvertent
      infusion of chemotherapeutic agents into the hemithorax of a patient with ovarian
      carcinoma. With the increasingly common use of outpatient intravenous therapy,
      emergency department presentations of unusual pleural effusions should be
      considered.

PMID- 9517695
TI  - Bilateral emphysematous pyelonephritis.
AB  - In any diabetic patient being diagnosed or treated for pyelonephritis, it is
      important to exclude the diagnosis of emphysematous pyelonephritis, which carries
      a high mortality rate. The authors present an illustrative case of emphysematous
      pyelonephritis treated with antibiotics and emergency nephrectomy. The signs,
      symptoms, pathophysiology, diagnosis, and treatment of emphysematous
      pyelonephritis are discussed.

PMID- 9517696
TI  - Endotracheal flumazenil: a new route of administration for benzodiazepine
      antagonism.
AB  - The purpose of this study was to determine if flumazenil is absorbed from broncho
      pulmonary tissue after intratracheal administration and whether therapeutically
      significant plasma concentrations can be obtained. Six elective surgical patients
      received a dose of 1.0 mg flumazenil in 10 mL saline intratracheally during
      general anesthesia. Blood samples were drawn for 6 hours after administration and
      plasma concentrations were determined by gas chromatography-mass spectrometry (GC
      MS). An average peak plasma flumazenil concentration of 65.9 +/- 43.1 ng/mL was
      attained within 1 minute after administration. No patients reported chest
      discomfort or dyspnea upon awakening and there were no other side effects noted.
      Administration of flumazenil via an endotracheal tube results in rapid attainment
      of therapeutic blood levels.

PMID- 9517697
TI  - Diagnosis of hip fracture by the auscultatory percussion technique.
AB  - Traumatic hip pain is a commonly encountered complaint in the emergency
      department. Occasionally, initial radiographs fail to show a fracture. A delayed
      diagnosis can result in significant patient morbidity. Diagnostic algorithms have
      been formulated to evaluate the patient with hip pain and negative initial
      radiographs. The auscultatory percussion technique can alert the physician of the
      presence or absence of an occult hip fracture. Consequently, the physician may
      order a more sophisticated imaging technique.

PMID- 9517698
TI  - Xiphodynia masking acute myocardial infarction: a diagnostic cul-de-sac.
AB  - A 52-year-old hypertensive woman is described in whom a clinically evident
      diagnosis of xiphodynia, the painful xiphoid process, complicated the diagnosis
      of impending myocardial infarction. The authors suggest that xiphodynia be
      considered a second-line assumption after more dangerous conditions have been
      thoroughly ruled out.

PMID- 9517699
TI  - Traumatic internal carotid artery dissections caused by blunt softball injuries.
AB  - This report describes recently treated patients with carotid artery dissection
      caused by blunt softball injuries, as well as the results of a study of carotid
      artery trauma in a community. Data obtained through the medical records linkage
      system used for epidemiologic studies in Olmsted County, MN were used to identify
      all cases of traumatic internal carotid artery dissection diagnosed from 1987
      through 1994. Four patients with traumatic internal carotid artery dissections
      were identified during the 8-year period under study. In two patients (50%) the
      carotid dissection was a result of the direct impact of a softball. A 39-year-old
      man, who developed transient cerebral ischemic symptoms, and a 35-year-old woman,
      who developed a painful Horner's syndrome, were struck by a softball on the
      anterolateral aspect of the neck. Both patients had a low carotid bifurcation.
      These data suggest that internal carotid artery dissections may be
      underrecognized sequelae of direct softball injuries to the anterolateral neck. A
      low carotid bifurcation may be a risk factor for such injuries.

PMID- 9517700
TI  - Colposcopy in evaluation of the adult sexual assault victim.
AB  - The purpose of this study was to determine if the colposcope improves detection
      of genital trauma in adult women who are victims of sexual assault compared with
      gross visual examination alone. A prospective, 1-month pilot study was conducted
      of 17 women patients who presented consecutively to Charity Hospital New Orleans
      during April 1994 requesting sexual assault examinations. Use of the colposcope
      allowed documentation of trauma in 9 of the 17 sexual assault victims (53%),
      compared with 1 of 17 (6%) by gross visualization alone (statistically
      significant: chi2 = 0.64, P = .0114). The colposcope improved detection of
      genital trauma in adult female sexual assault victims as compared with gross
      visual examination alone at a statistically significant level.

PMID- 9517701
TI  - Takayasu arteritis presenting as amaurosis fugax in a man.

PMID- 9517702
TI  - Preexcitation in infancy and childhood.

PMID- 9517703
TI  - Cases in electrocardiography.

PMID- 9517704
TI  - A revised decision analysis of strategies in the management of febrile children
      at risk for occult bacteremia.
AB  - Two decision analysis reports published in 1991 concluded that the strategy of
      routine blood culture and empiric antibiotics was the superior strategy for
      febrile children at risk for occult bacteremia. This report describes a decision
      analysis of treatment strategies for these children considering the following
      changes that have occurred since then: (1) Hemophilus influenzae B incidence is
      low because of widespread vaccine use; (2) the emergence of resistant
      Streptococcus pneumoniae may affect the clinical effectiveness of empiric
      antibiotics in the future; and (3) the negative consequences of unnecessary
      antibiotic treatment have yet to be well defined. A decision analysis approach,
      modifying the original assumptions, was carried out. Sensitivity analyses were
      conducted on all assumption variables. Strategies employing empiric antibiotics
      were found to have the best outcomes, assuming low negative treatment
      consequences. If a high level of negative treatment consequences is assumed,
      strategies using a white blood cell count (WBC) are superior. If a very high
      level of negative treatment consequences is assumed, the strategy of no tests and
      no empiric antibiotic treatment is usually superior, unless the frequency of
      bacteremia is 10% or higher and empiric antibiotic efficacy is high, in which
      case a WBC strategy is superior. This information can be used to select a
      treatment strategy based largely on the estimation of the negative consequences
      of treatment.

PMID- 9517705
TI  - Research and barbaric medicine.

PMID- 9517706
TI  - Characteristics of prehospital cardiac arrest patients in Japan and determinant
      factors for survival.
AB  - Two hundred forty-seven consecutive patients who had prehospital cardiac arrest
      and were transferred to a municipal hospital were studied to elucidate the
      characteristics of these patients and to investigate factors for improving the
      survival rate among prehospital cardiac arrest patients. Detailed information on
      130 patients with cardiac etiology was analyzed: 110 were confirmed dead in the
      emergency department (group A); 14 survived less than 1 week (group B); 6
      survived longer than 1 week (group C). Only one patient received cardiopulmonary
      resuscitation (CPR) from a bystander, and none received electrical defibrillation
      before arriving at hospital because, at the time, emergency personnel were not
      allowed to perform advanced life support (ALS) in Japan. The three
      characteristics for better prognosis after prehospital cardiac arrest were found
      to be as follows: being witnessed on collapse, receiving prompt ALS, and
      ventricular fibrillation on arrival at hospital. The survival rate would have
      been higher if more lay people could have performed CPR and if emergency unit
      personnel had been allowed to perform ALS.

PMID- 9517707
TI  - Acute blindness after severe quinine poisoning.

PMID- 9517709
TI  - Tophaceous lumbar gout mimicking an epidural abscess.

PMID- 9517708
TI  - Heliox in the treatment of obstructive hypoventilation.

PMID- 9517710
TI  - Charity begins at home...

PMID- 9517711
TI  - Orthodontic Centers of America.

PMID- 9517712
TI  - Treatment planning.

PMID- 9517713
TI  - Predicting functional appliance treatment outcome in Class II malocclusion.

PMID- 9517714
TI  - Perioral forces and dental changes resulting from mandibular lip bumper
      treatment.
AB  - This prospective study compares pretreatment and posttreatment forces produced by
      a lip bumper on the mandibular first molars and determines the dental effects of
      this appliance after 1 year of treatment. Twenty-five patients, ages 10 to 17
      years, received fixed 0.045-inch passive stainless steel lip bumpers positioned
      at the level of the gingival margin, 2 mm from the labial surface of the teeth as
      the only form of treatment in the mandibular arch. At the end of 1 year,
      cephalometric radiographs and dental casts were taken, and lower lip forces
      remeasured during rest, speech, and swallowing. Lip force measurements were
      performed using specially designed strain gauges mounted bilaterally in the lip
      bumper tubes. Measurements of lip forces made before and after treatment were
      compared to explore the changes, if any, due to muscle adaptation to the
      appliance. Dental changes were measured from casts and cephalometric radiographs.
      Correlation analyses were performed to determine whether a relationship existed
      between initial force levels and resulting tooth movement. Pretreatment and
      posttreatment forces did not demonstrate a statistically significant difference.
      On the other hand, measurement of the dental casts revealed a significant
      increase in arch length caused by incisor proclination and protrusion, combined
      with molar distalization. The arch width significantly increased at the canines,
      first and second premolars, and first molars. The amount of force exerted by the
      lower lip on the molars was not correlated to the degree of tooth movement
      recorded in this sample.

PMID- 9517715
TI  - The effect of second-order couple on the application of torque.
AB  - Complex combinations of linear forces, moments, and couples are developed by the
      arch wire during orthodontic treatment. For instance, application of torque to a
      canine during distal driving may create force interactions if the tooth tips
      distally toward the extraction site. This investigation studied the effect of
      second-order couples and bracket angulations on the application of torque to a
      single tooth. By using a test apparatus to simulate application of torque to a
      single tooth, 0.016 x 0.022 inch stainless steel wires were tested in
      longitudinal torsion simultaneous to fixed amounts of second-order couples or
      fixed degrees of second-order bracket angulation. Application of a second-order
      couple through a bracket to a longitudinally twisted arch wire produces a third
      order couple, since the bracket slot walls exert forces on the wire, tending to
      detwist it. This third-order couple will usually be small as the distance between
      the two couple members is short. Nevertheless, it may have a restraining effect
      on the third-order wire-bracket interaction. The results show that application of
      second-order couples or bracket angulations lead to an increase in exerted torque
      for angles of twist below 22 degrees. Because of torsional play, a wire twisted
      18 degrees in a 0.018-inch bracket slot did not exert any torque unless it was
      subjected to a second-order couple. Thus, in an in vivo situation where forces
      interact, the actual torsional play may be substantially less than predicted from
      theoretical models only regarding third-order mechanics. The restraining effect
      of second-order couples tapered when the torque created by longitudinal twisting
      became much larger than the torque exerted by the second-order couple. Second
      order couples of biologically acceptable magnitudes had little effect on the
      level of torque after the third-order clearance had been eliminated.

PMID- 9517716
TI  - The validity of two methods of mandibular superimposition: a comparison with
      tantalum implants.
AB  - The aim of this investigation was to examine and compare the validity of Bjork's
      and Ricketts' methods for the superimposition of serial cephalometric radiographs
      of the mandible for the analysis of changes over the duration of routine
      orthodontic treatment in growing subjects (approximately 2 years). Pre- and
      posttreatment lateral cephalometric radiographs of 23 children, with tantalum
      markers implanted in the mandible, were studied. The differences in position of
      six dental and skeletal landmarks between superimposition on Bjork's structures
      and on Ricketts' corpus axis were compared with those on the basis of the
      implants. A rotational effect was found for corpus axis resulting from
      differential movement of Xi point with growth, whereas Bjork's method yielded
      results essentially similar to those of the implant-based superimposition. This
      resulted in statistically significant median differences between the two methods
      for all landmarks except pogonion and menton. The magnitude of the differences
      increased with distance from the central core of the mandible and were generally
      greater horizontally than vertically. Although most differences were less than 2
      mm, approximately 10% of the subjects showed differences greater than 4 mm for
      molar and incisor landmarks. These findings suggest that, for growing subjects,
      Bjork's method should be preferred Ricketts', which cannot be relied on to
      indicate the true (intramandibular) changes during orthodontic treatment in
      growing subjects.

PMID- 9517717
TI  - An in vivo comparison between a visible light-cured bonding system and a
      chemically cured bonding system.
AB  - Direct bonding of brackets has become a routine procedure in clinical
      orthodontics. Many techniques and materials are currently advocated and used, the
      most recent being light-cured composites. Advantages of the light-cured systems
      are their relative ease of use, improved bracket placement, and more rapid set of
      the composite. For a new system to be clinically viable, it must possess
      properties that are at least as reliable as existing systems. The purpose of this
      longitudinal clinical study was to evaluate and compare the rate of success
      and/or failure between a visible light-cured bonding material (Sequence) and a
      chemically cured bonding material (System 1+), using both systems in every
      patient. Contralateral quadrants were bonded with each system respectively. A
      total of 32 patients were followed for a mean period of 11 months (range of 3 to
      21 months), with a total of 531 brackets bonded, 265 with visible light-cured and
      266 with chemically cured resins. Failures for each system were recorded and
      failure rates calculated. The failure rate of the visible light-cured composite
      was 11.3% and that of the chemically cured composite was 12%. A Chi-squared
      (chi2) test did not reveal any statistically significant differences between the
      failure rates of the two systems, (chi2 = 0.014, df-1, P > 0.9).

PMID- 9517718
TI  - The relationship between bond strength and orthodontic bracket base surface area
      with conventional and microetched foil-mesh bases.
AB  - The aim of this study was to test the effects on the shear bond strength by
      sandblasting bracket base surfaces, reducing base surface area, and etching
      enamel with various acid types. Four different base sizes, used as either
      standard (untreated), sandblasted or microetched were bonded with Phase II resin
      (Reliance Orthodontic Products, Inc.) in four groups of 12 bovine enamel
      specimens after enamel etching with phosphoric acid gel (37%), 37% phosphoric
      acid aqueous solution, 10% maleic acid gel, or 10% maleic acid aqueous solution.
      Storage of samples was for 7 days in distilled water at room temperature before
      shear bond testing with an Instron universal testing machine with a crosshead
      speed of 0.5 mm/min. Statistical analyses included the analysis of variance, the
      Student t test, and the Chi-square test at p < 0.05. An increase in shear bond
      strength was associated with sandblasting and microetching of foil-mesh bases for
      all base sizes (p < 0.05). No statistically significant difference in shear bond
      strength existed between the three larger base sizes, which indicated that shear
      bond strength is independent of surface area between 6.82 and 12.35 mm2. A
      reduction in bond strength was associated with the reduction of base surface area
      from 6.82 to 2.38 mm2 (p < 0.05). There appears to be no need to increase base
      surface area beyond 6.82 mm2. Aqueous maleic acid (10%) etching of the enamel was
      associated with the highest shear bond strength, with no statistically
      significant difference between the other three acids used.

PMID- 9517719
TI  - Metal strength of direct bonding brackets.
AB  - Because the strength of direct bonding brackets is both important and difficult
      to measure, a related property, microhardness, has been investigated. Twelve
      popular U.S. brands of direct bonding brackets have been tested with a Vickers
      Hanemann microhardness apparatus. The tests have shown a consistently wide
      difference in hardness between brands, the highest values being exhibited by
      those using the precipitation hardened steel known as PH 17-4, and the lowest by
      those using the austenitic 316L. As the first steel proved to be significantly
      less corrosion resistant than the last one, it seems that today there are too few
      attachments that are both strong and chemically resistant.

PMID- 9517720
TI  - Validity of using fixation screws/wires as alternative landmarks for
      cephalometric evaluation after LeFort I osteotomy.
AB  - The most widely used method to measure postoperative stability of a surgically
      repositioned bony segment is based on skeletal landmarks. Unfortunately,
      orthognathic surgery may alter the skeletal landmarks and bony configurations
      that are commonly used for cephalometric analysis. Intraosseous wires, plates,
      and screws are routinely used in orthognathic surgery, and postoperatively they
      are easier to identify than skeletal landmarks. Cephalometric radiographs from 25
      adult patients, who had undergone LeFort I one piece osteotomy, were used to
      analyze the validity of fixation wires/screws used as landmarks to evaluate
      postoperative stability of the maxilla. The positional changes of maxillary
      skeletal landmarks (A point and anterior and posterior nasal spines) and
      intraosseous fixation wires/screws were measured relative to the cranial base.
      The fixation screws/wires were also measured relative to the invariant maxillary
      trabecular patterns and palatal plane from 1 to 6 weeks (T1-T2) and 6 weeks to 1
      year postoperatively. The reproducibility of fixation wires/screws was found to
      be higher than that of skeletal landmarks. The fixation wires/screws remained
      stable in the maxilla; their postoperative positional changes were not
      significantly different from those of the skeletal landmarks. When the skeletal
      landmarks are altered or no longer exist after LeFort I osteotomy, fixation
      wires/screws could be used as alternative landmarks to measure the maxillary
      postoperative stability.

PMID- 9517721
TI  - Mixed dentition analysis for Asian-Americans.
AB  - One of the important aspects of diagnosis in the mixed dentition is the
      determination of the tooth size-arch length relationship. Such a determination is
      often made before eruption of the permanent canines and first and second
      premolars. The most commonly used prediction method of Tanaka and Johnston is
      based on data from a sample of children of Northern European descent. The
      accuracy of this method when applied to a different ethnic population is
      questionable. In this study, 201 dental plaster casts of Asia-Pacific-American
      subjects, all of whom were under the age of 21 years, were used. The actual
      measurements were compared with the predicted values derived from the Tanaka and
      Johnston equations and significant differences were found. The data illustrate
      the limitations of the Tanaka and Johnston method when applied to a sample
      population of other than European descent. From this data, two linear regression
      equations were developed for tooth size prediction in Asian-American children.

PMID- 9517722
TI  - Evaluation of orthodontic relapse using the cubic spline function.
AB  - A sample of 72 orthodontically treated patients was reexamined many years out of
      retention. They had been treated either by the extraction of four premolars or
      without extractions. The average number of years between the end of treatment and
      the taking of follow-up records was 20, with a range of 12 to 35 years. Some
      conventional measurements were studied such as intertooth widths, arch perimeter,
      and incisor irregularity. In addition, a new method for comparison of arch form
      at different stages of treatment, which uses the cubic spline function, was used.
      Cases were grouped into extraction and nonextraction, and statistics were used to
      test the differences between the two groups. Correlations between the spline
      variables and conventional variables were computed, and multiple regression
      analysis was carried out using the spline variables as dependent variables. Some
      treatment and relapse changes were independent of whether the case was treated
      with extractions or not, whereas other trends were unique to one treatment group.
      The correlation analysis revealed strong relationships between variables that
      measured changes during the same treatment stage. There were also moderate
      correlations between some of the spline variables and the traditional
      measurements. Multiple regression analysis was used to account for changes in
      some spline variables, however, the usefulness of the model as a predictor is
      limited.

PMID- 9517723
TI  - Analysis of change in arch form with premolar expansion.
AB  - The arch forms of 38 cases (53 nonextraction and 23 extraction arches) in which
      expansion, while maintaining arch form, was the objective of the practitioner,
      were analyzed before treatment, after treatment, and an average of 6 to 8 years
      after retention. The cubic spline was used to fit a curve representing arch form.
      By superimposing the spline curves, changes in arch form were analyzed with the
      variables rebound change (RC), rebound index (RI), rebound number (RN), and
      stability number (SN). Traditional linear intraarch dimensions were also
      analyzed. Analysis of variance was used to determine differences between the
      maxillary and mandibular arches and between the extraction and nonextraction
      cases. Pearson correlation coefficients between spline variables and arch width
      variables were also computed. There was significantly more expansion in the
      maxillary arch than the mandibular arch during treatment, irrespective of
      extraction or nonextraction strategies. In the nonextraction cases, a greater
      amount of net expansion was achieved for all dimensions for the maxillary arch as
      compared with the mandibular arch. Overall, a relatively high stability in arch
      form was found. The findings suggest that stability may not be related to the
      amount of change produced during treatment. Significant expansion can be gained
      throughout the premolar regions and may be expected to be stable. The order of
      greatest net arch width gained was for the second premolars followed by first
      premolars, molars, and then the canines. The intercanine widths for both arches
      decreased toward pretreatment values, but were more stable in the maxillary arch
      in nonextraction cases. The cubic spline permits measurement of change in arch
      form both during treatment and retention periods.

PMID- 9517724
TI  - Effects of different vectors of forces applied by combined headgear.
AB  - The effects of various directed forces applied by combined headgear were
      evaluated in this study. The study material consisted of 30 patients with Class
      II dental relationships and steep mandibular plane angles. Three groups of 10
      patients each were formed. In the first treatment group, forces of 150 gm per
      side were used for the high-pull component and the cervical component. In the
      second treatment group, forces of 200 gm per side for the high-pull component and
      100 gm per side for the cervical component were applied. In the third treatment
      group, forces of 100 gm per side were applied for the high-pull component and 200
      gm per side for the cervical component. Distal tipping of upper molar was
      greatest in the third treatment group. Intrusion of the upper molar in the second
      treatment group and extrusion of the upper molar in the third treatment group
      were statistically significant. Changes in occlusal and mandibular plane angles
      showed significant differences between the groups.

PMID- 9517725
TI  - International comparisons of professional assessments in orthodontics: Part 2-
      treatment outcome.
AB  - The opinion of 97 orthodontists in 9 countries has been surveyed with respect to
      the judgment of treatment outcome. Ninety-eight pretreatment and posttreatment
      study casts were examined by each orthodontist who gave a judgment of the degree
      of improvement and whether they thought the result was acceptable. It was found
      that there was at least 80% agreement on the acceptability of the outcome for
      only 45.5% of the sample. Logistic regression was used to identify predictive
      indicators for the judgment of acceptance. It was found that the posttreatment
      scores for dental esthetics, crossbite, buccal segment sagittal relation, lower
      arch crowding, centerline, and left and right buccal segment vertical
      relationship were most important predictor variables. These six traits correctly
      assigned the decision with 70% accuracy. The judgment of outcome did not seem to
      take account of the treatment complexity as judged by the practitioners. It was
      also found that judgments are significantly affected by the country and payment
      methods, practice environment, and experience of the practitioner. The occlusal
      traits identified can be usefully incorporated into a index for assessing both
      treatment need and outcome, and may serve the purposes for audit and research in
      orthodontics.

PMID- 9517726
TI  - Posttreatment assessment of surgically exposed and orthodontically aligned
      impacted maxillary canines.
AB  - The records of 96 consecutively treated patients, with a total of 110 exposed
      maxillary canines, were reviewed after orthodontic alignment of the exposed
      teeth. In view of the high degree of clinical and patient satisfaction with the
      results, a random sample of 25 patients, with a total of 30 exposed canines, were
      critically assessed. The assessment involved scoring for clinical impression,
      mobility, gingival condition and pocketing, oral hygiene, vitality, and
      radiographic appearances. The results indicate that the technique of surgical
      exposure and orthodontic alignment of ectopic maxillary canines provides a
      satisfactory method of treatment.

PMID- 9517727
TI  - Skeletal effects of early treatment of Class III malocclusion with maxillary
      expansion and face-mask therapy.
AB  - The effectiveness of maxillary expansion and face-mask therapy in children with
      Class III malocclusion was studied in a sample of 46 subjects in mixed dentition
      and compared with a control sample of 32 subjects with untreated Class III
      malocclusion. Treated and untreated samples were divided into early and late
      mixed-dentition groups to aid identification of the optimum timing of the
      orthopedic treatment of the underlying skeletal disharmony. Cephalometric
      analysis was based on a stable basicranial reference system, appropriate for
      longitudinal studies started in the early developmental ages. The level of
      significance for intergroup comparisons was set at a p value of 0.01. Significant
      forward displacement of the maxillary complex was found in the early-treatment
      group. The region of the pterygomaxillary suture, in particular, showed
      significant changes in the subjects treated during early mixed dentition. No
      significant maxillary modifications were recorded in the late-treatment group.
      Both early and late groups exhibited smaller increments in mandibular protrusion
      and larger increments in the intermaxillary vertical relationship compared with
      their respective Class III control groups. Only children treated at an early age,
      however, showed a significant upward and forward direction of condylar growth,
      leading to smaller increments in total mandibular length. These results indicate
      that the combination of a bonded maxillary expander and face-mask therapy is more
      effective in early mixed dentition than in late mixed dentition, especially with
      regard to the magnitude of the protraction effects on maxillary structures.

PMID- 9517728
TI  - The nature of arch width difference and palatal depth of the anterior open bite.
AB  - Measurements were made of study casts of patients with anterior open bite to
      compare the width of maxillary and mandibular arches and the depth of the palate.
      This study was designed to (1) explore the nature of the arch width difference
      for patients with anterior open bite, whether dental or skeletal in nature, and
      (2) clarify the general impression of "high" palatal vaults for anterior open
      bite cases, to make sure if there are "absolutely high" or "relatively high"
      palatal vaults. Measurements in male and female patients with open bite
      malocclusions were analyzed and compared with those in male and female patients
      with normal occlusions. Similar trends were found for both sexes. Skeletally
      narrowed maxillary posterior width and dentally widened mandibular posterior
      widths were found. Palatal depth was in the normal range in the patients with
      anterior open bite. Orthopedic widening of the maxillae and inclining of the
      mandibular posterior teeth lingually are recommended when orthodontic treatment
      is to be rendered to patients with anterior open bite.

PMID- 9517729
TI  - Use of nickel titanium closed-coil springs to align unerupted teeth: a case
      report.
AB  - We describe a case in which a patient with a class II division I incisor
      relationship on a skeletal II base was transferred midway through a treatment
      that consisted of aligning the upper and lower arches with fixed appliance
      orthodontics in preparation for a mandibular advancement osteotomy. The lower
      second molars had previously been extracted; the lower third molars were left
      unerupted and some distance from the lower first molars. To provide a good
      occlusion at the end of treatment, it was decided to expose and approximate the
      lower third molars to the distal aspect of the lower first molars with the use of
      nickel titanium closed-coil springs; this was to be done before the osteotomy.

PMID- 9517730
TI  - Video-imaging and treatment presentation: medico-legal implications and patient
      perception.

PMID- 9517731
TI  - Orthodontics as a spectator sport: does bystander liability attach? [corrected].

PMID- 9517732
TI  - Simeon Hayden Guilford (1841-1919).

PMID- 9517733
TI  - Pyogenic liver abscesses in patients with malignant disease: a report of 52 cases
      treated at a single institution.
AB  - BACKGROUND: Prognosis of pyogenic liver abscesses in patients with malignant
      disease is generally considered poor. The discrepancy between the outcomes of
      liver abscesses caused by hepatopancreatobiliary malignant disease and those
      caused by other malignant diseases, however, to our knowledge has never been
      investigated. OBJECTIVES: To clarify the clinical course of pyogenic liver
      abscess in patients with different types of cancer, and to compare outcomes in
      abscesses caused by hepatopancreatobiliary malignant disease and other malignant
      disease. DESIGN: Retrospective review of case series in our experience from 1980
      through 1993. SETTING: Tertiary care university teaching hospital. PATIENTS:
      Fifty-two patients with pyogenic liver abscess related to the underlying cancer
      were divided into 2 groups. Group 1 (n=32) was composed of patients with cancer
      originating from the hepatic parenchyma, bile duct, and pancreas; group 2 (n=20)
      was composed of patients with cancer originating from other sites. INTERVENTIONS:
      Parenteral antibiotics, percutaneous drainage, surgical drainage, or hepatectomy,
      in combinations, were employed. MAIN OUTCOME MEASURES: Patient characteristics,
      symptoms, laboratory data, abscess characteristics, microbiological study,
      management, and outcome of the 2 groups were analyzed. RESULTS: Thirteen patients
      (41%) in group 1 and 16 patients (80%) in group 2 had undergone prior anticancer
      treatment. Jaundice was encountered more often in group 1 than in group 2 (29
      patients [91%] vs 6 patients [30%], respectively, P=.001), whereas nausea and
      vomiting were more frequently seen in group 2 than in group 1 (17 patients [52%]
      vs 6 patients[31%], respectively, P=.04). Leukocytosis, hypoalbuminemia,
      hyperbilirubinemia, and reversed albumin-globulin ratio were more pronounced in
      group 1 than in group 2 (P=.001, .02, .003, and .03, respectively). Abscesses
      communicating with the intrahepatic biliary tree were more frequently encountered
      in group 1 than in group 2 (11 patients [34%] vs 2 patients [10%], respectively,
      P=.03). Escherichia coli and Klebsiella pneumoniae predominated in group 1, while
      the bacteria species in group 2 were more diverse. The hospital mortality rates
      of group 1 and group 2 were 28% (9 of 32 patients) vs 10% (2 of 20 patients)
      (P=.04), respectively. Twenty-three patients (72%) of group 1 died of
      uncontrolled biliary sepsis or progressive cancer or both within 6 months after
      the diagnosis, while 17 patients (85%) of group 2 survived longer than 1 year
      without relapse of the abscess and continued with anticancer treatment.
      CONCLUSIONS: Pyogenic liver abscess could be a presentation of
      hepatopancreatobiliary malignant disease at the preterminal stage, and carries a
      grave prognosis. Pyogenic liver abscess in patients with
      nonhepatopancreatobiliary malignant disease has a better chance of favorable
      outcome.

PMID- 9517734
TI  - Response of normal aorta to endovascular grafting: a serial histopathological
      study.
AB  - OBJECTIVE: To examine the histological changes caused by the presence of the
      endovascular stented graft in the native aorta. DESIGN AND INTERVENTION: Case
      series. Twenty Western crossbred adult male sheep underwent endovascular
      placement of an infrarenal aortic stented graft, using the Bard aortic aneurysm
      repair device catheter delivery system (Bard Vascular Systems, Dovermill, Mass).
      Six self-expanding wire hooks at the proximal anchor allow fixation to the aorta.
      After 1 month (n=6), 3 months (n=6), and 6 months (n=8), the animals underwent
      repeated angiography and intravascular ultrasonography to study the aorta and the
      graft. The aorta was explanted en bloc with the left renal artery, pressure
      perfused with a formalin gluteraldehyde solution, and then underwent histological
      examination with hematoxylin-eosin, trichrome, and elastic tissue staining. MAIN
      OUTCOME MEASURES: Description of histological changes at various intervals after
      endovascular stented graft placement. RESULTS: Significant histological findings
      include (1) complete incorporation of the grafts into the aortic wall, with a
      pseudointima of smooth muscle cells and collagen; (2) a foreign-body reaction
      around the graft; (3) an organized blood clot noted between the graft and the
      aortic wall, without evidence of recent blood flow through the perigraft space or
      the lumbar vessels; and (4) focal replacement by collagen of the inner one third
      to one half of the media at the proximal anchor sites. CONCLUSION: There was good
      incorporation of the graft without evidence of pressure necrosis, bleeding around
      the graft, or flow in the occluded lumbar vessels.

PMID- 9517736
TI  - Increased systemic inflammation after laparotomy vs laparoscopy in an animal
      model of peritonitis.
AB  - OBJECTIVE: To study the influence of laparotomy and laparoscopy on local and
      systemic inflammation in a rat model of peritonitis. DESIGN: Bacteremia,
      peripheral leukocyte subpopulations, tumor necrosis factor alpha (TNF-alpha)
      plasma levels, and ex vivo secretion of peripheral blood mononuclear cells were
      investigated after laparotomy and laparoscopy in a prospective randomized
      experimental study. SETTING: Surgical department of a university hospital.
      ANIMALS: 60 male inbred Wistar rats. INTERVENTIONS: Standardized fecal inoculum
      was injected intraperitoneally and rats underwent laparotomy (n=20), laparoscopy
      (n=20), or no further manipulation (control group, n=20). Blood samples were
      obtained during the perioperative course to determine bacteremia, leukocytic
      subpopulations, TNF-alpha plasma levels, and ex vivo secretion. The number of
      intraperitoneal abscesses was determined in each animal after 1 week. MAIN
      OUTCOME MEASURE: The hypothesis of the experiment was that laparoscopy with
      carbon dioxide leads to an increase of local and systemic inflammation in
      comparison with the laparotomy and control groups. RESULTS: One hour after
      intervention, bacteremia was significantly higher in the laparotomy and
      laparoscopy groups compared with the control group (P=.01). Fecal inoculum caused
      significant monocytopenia and lymphocytopenia in all groups within 1 hour after
      intervention (P<.05), with complete recovery on day 2 only in the laparoscopy and
      control groups. Laparotomy caused a significant increase in TNF-alpha plasma
      levels and decrease of ex vivo production of TNF-alpha compared with the other 2
      groups (P<.05). CONCLUSIONS: Laparotomy and laparoscopy increased the incidence
      of bacteremia and systemic inflammation in this peritonitis model. The
      inflammatory response was significantly higher in the laparotomy group compared
      with the laparoscopy group.

PMID- 9517735
TI  - Effects of sucralfate vs antacids on gastric pathogens: results of a double-blind
      clinical trial.
AB  - BACKGROUND: Unblinded studies suggested that sucralfate prophylaxis for stress
      ulcers is associated with a lower rate of nosocomial pneumonia than acid-reducing
      approaches. We performed a randomized, double-blind, double-sham clinical trial
      comparing the exact microbial effects of each treatment. METHODS: One hundred
      forty patients entered this study before major elective surgery, allowing
      baseline cultures of gastric and pulmonary secretions to be obtained
      intraoperatively. Postoperatively, the patients were treated with standard doses
      of either sucralfate or antacids, plus a sham of the other drug. Cultures were
      repeated twice daily for 3 days. Molecular epidemiological typing was used to
      track the appearance of specific microbes and their transmission from site to
      site, and clinical end points were compared. The number of patients chosen was
      for sufficient statistical power to detect differences in the microbial measures,
      as detecting differences in clinical measures would have required increasing the
      sample size by an order of magnitude. RESULTS: Gastric pH was affected by the
      form of stress ulcer prophylaxis throughout the study, and this pH effect
      affected the number of new gastric organisms appearing in the 2 different groups.
      Colonization of the airway with new gastric organisms occurred more frequently in
      the antacid than in the sucralfate group, and colonization of the airway with
      organisms of gastric origin was associated with occurrence of postoperative
      pneumonia. CONCLUSIONS: Both sucralfate and antacids offered safe and effective
      stress ulcer prophylaxis in this double-blind clinical trial of postoperative
      patients in an intensive care unit. In association with the drug's effects on
      gastric pH, more new pathogens appeared in the gastric contents of antacid
      treated than sucralfate-treated patients.

PMID- 9517737
TI  - Intraoperative pancreatoscopy with the ultrathin pancreatoscope for mucin
      producing tumors of the pancreas.
AB  - OBJECTIVE: To evaluate the diagnostic accuracy of intraoperative pancreatoscopy
      with the ultrathin pancreatoscope for the main pancreatic lesions of mucin
      producing tumors of the pancreas (MPT). DESIGN: Prospective diagnostic test study
      with a criterion standard of pathologic examination and masked comparison.
      SETTING: A university hospital. PATIENTS: Twenty-four consecutive patients with
      MPT referred for surgery in whom endoscopic retrograde pancreatography,
      endoscopic ultrasonography, and computed tomography had been performed as a
      diagnostic examination. All patients underwent surgery and the diagnosis was
      confirmed by pathologic examination. INTERVENTION: Intraoperative pancreatoscopy
      was performed with the ultrathin pancreatoscope. MAIN OUTCOME MEASURES: Findings
      of intraoperative pancreatoscopy, endoscopic retrograde pancreatography, and
      endoscopic ultrasonography were confirmed by pathologic examination of resected
      specimens. The diagnostic accuracy of these 3 modalities in detection of MPT
      lesions in the main pancreatic duct was compared. RESULTS: The diagnostic
      criterion of MPT lesions in the main pancreatic duct by intraoperative
      pancreatoscopy was a granular and papillary mural nodule. An MPT lesion in the
      main pancreatic duct was found in 17 of 24 cases. Intraoperative pancreatoscopy
      detected 10 cases of intraductal MPT lesions that could not be detected by
      endoscopic ultrasonography or endoscopic retrograde pancreatography. Five of 10
      cases were intraductal multicentric lesions. In 3 of these 5, additional
      pancreatic resection was performed. For diagnosis of MPT lesions, the
      sensitivity, specificity, and overall accuracy of intraoperative pancreatoscopy
      were all 100%; respective values were 43.8%, 100%, and 60.9% for endoscopic
      retrograde pancreatography and 47%, 100%, and 62.5% for endoscopic
      ultrasonography. CONCLUSIONS: Intraoperative pancreatoscopy is safe and effective
      in diagnosing the intrapancreatic duct extension and multicentric lesions of MPT.
      It provides important information for operative strategy and contributes to
      successful pancreatic surgery.

PMID- 9517738
TI  - Long-term evaluation of modified lateral anorectal myomectomy for low-segment
      Hirschsprung disease.
AB  - OBJECTIVES: To provide a simple myomectomy technique for low-segment Hirschsprung
      disease and evaluate the efficacy of the new modification. DESIGN: Case series of
      19 patients followed up for 12 to 56 months (mean, 39.1 months). SETTING: Tanta
      University Hospital, Tanta, Egypt. PARTICIPANTS: Nineteen patients aged 4 months
      to 10 years complaining of chronic constipation, with radiological and clinical
      data suggestive of low-segment Hirschsprung disease proven by histological
      examination. INTERVENTION: Modified lateral anorectal myomectomy. MAIN OUTCOME
      MEASURES: Clinical and radiological improvement measured by postoperative barium
      enema, bowel habits, and patient's relief of symptoms. RESULTS: Seventeen of 19
      patients improved clinically and 13 showed radiological improvement 3 years
      postoperatively. There was poor response in 2 patients, who were subjected to
      further Soave procedures. CONCLUSION: Modified lateral anorectal myomectomy is an
      effective and technically simple procedure in patients suspected of having low
      segment Hirschsprung disease.

PMID- 9517739
TI  - Extraperitoneal laparoscopically assisted ilioinguinal lymphadenectomy for
      treatment of malignant melanoma.
AB  - BACKGROUND: Current treatment of malignant melanoma of the leg includes
      ilioinguinal lymphadenectomy (IIL). Standard open IIL (open IIL) includes
      sectioning of the inguinal ligament to gain access to the iliac nodes.
      Extraperitoneal laparoscopic IIL (lap IIL) is a feasible, less aggressive
      approach. It can be combined with standard superficial lymphadenectomy for
      treatment of malignant melanoma. DESIGN: Comparative, prospective, nonrandomized
      series. SETTING: Tertiary care center. PATIENTS: Twelve consecutive, unselected
      patients with malignant melanoma treated with lap IIL (group 1) were compared
      with 10 consecutive, unselected patients with malignant melanoma on whom open IIL
      was performed (group 2). INTERVENTIONS: Standard open IIL and laparoscopic
      extraperitoneal iliac lymphadenectomy (lap IIL) plus superficial groin
      lymphadenectomy. MAIN OUTCOME MEASURES: Operative time, intraoperative
      complications, requirements of analgesia, total volume of lymphatic drainage,
      number of lymph nodes retrieved, immediate morbidity, hospital stay, and long
      term morbidity were evaluated. RESULTS: Operative time was significantly longer
      for the lap IIL group (group 1) than for the open IIL group (group 2) (177+/-44
      vs 140+/-18 minutes, respectively; P<.05), but no patients in group 1 needed
      conversion to open surgery or developed related complications. Overall lymphatic
      drainage was significantly lower in group 1 than in group 2 (615+/-518 mL vs
      1393+/-793 mL, repectively; P<.01). The number of doses of analgesics (13+/-8 vs
      31+/-22, P<.03) and length of postoperative stay (7.3+/-3.3 vs 13+/-5 days,
      P<.006) were also significantly lower in the laparoscopic group. The overall
      number of lymph nodes retrieved was similar in both groups (10.2+/-4.6 vs 10+/-3,
      P=.9). One patient developed a groin hernia of 6 m after open IIL. CONCLUSIONS:
      Laparoscopically assisted IIL offers a less aggressive approach than open IIL and
      entails less pain and a shorter hospital stay, as we observed in 2 groups with
      similar oncological results (mainly, a similar number of lymph nodes retrieved)
      who were treated with one procedure or the other. Further research should be done
      to confirm these preliminary advantages in a prospective randomized trial with
      long-term follow-up.

PMID- 9517740
TI  - Papillary thyroid carcinoma: modified radical neck dissection improves prognosis.
AB  - OBJECTIVE: To ascertain whether modified radical neck dissection offers a
      survival advantage for some subsets of patients with papillary cancer of the
      thyroid. DESIGN: A retrospective cohort study of 2966 patients curatively treated
      at the Noguchi Thyroid Clinic and Hospital Foundation, Oita, Japan, between 1946
      and 1991. SETTING: A center for the treatment of thyroid disease, where about
      1400 thyroid operations are performed per year. PATIENTS: Between 1946 and 1991,
      patients with papillary cancer whose primary tumor was 1 cm or larger and who
      were curatively treated were studied. Of the 2859 patients, 72.1% underwent
      modified radical neck dissection, 8.5% underwent partial node excision, and 19.4%
      underwent no node excision. RESULTS: A univariate analysis revealed a subset of
      patients who benefited from modified radical neck dissection. A multivariate
      analysis revealed that sex (P<.001), age at the time of the operation (P<.001),
      size of the primary tumor (P<.001), extrathyroidal invasion (P<.001), and the
      presence of nodal metastasis (P<.01) are significant risk factors. CONCLUSION:
      Patients with nodal metastasis, patients in whom the primary tumor invades beyond
      the thyroid capsule, and women older than 60 years can benefit from modified
      radical neck dissection.

PMID- 9517741
TI  - Open pelvic fracture and fecal diversion.
AB  - BACKGROUND: Mandatory fecal diversion has been advocated as an appropriate
      measure to prevent infection in the clinical setting of an open pelvic fracture.
      However, the efficacy of this practice has not been verified by prospective
      investigation and has received only inconsistent support from retrospective
      analyses. OBJECTIVE: To determine whether fecal diversion is associated with a
      substantially lower incidence of abdominopelvic infectious complications in
      patients with open pelvic fractures. DESIGN: Case-control study. SETTING:
      University-based tertiary care, level I trauma center. METHODS: The current study
      reviews our experience with 60 cases admitted from 1987 to 1993 to Harborview
      Medical Center, a regional level I trauma center. Data collected on each patient
      included age, sex, Injury Severity Score, Glasgow Coma Scale, initial heart rate
      and systolic blood pressure, location and severity of wound, fracture pattern,
      pelvic stability, time to open reduction internal fixation or external fixation,
      mortality, use of fecal diversion, and incidence and location of infection.
      Review of the literature produced an additional 186 patients amenable to
      analysis. RESULTS: Fecal diversion was performed in 19 patients, 5 (26%) of whom
      experienced subsequent abdominopelvic infectious morbidity. Of the remaining 41
      patients, 7 patients (17%) experienced infectious complications. The 2 groups
      (diversion vs no diversion) were comparable with regard to relevant demographic
      and clinical characteristics of injury severity. Combining the present series
      with those reported by others gave a composite series of 246 patients. For the
      composite series, diversion was performed in 70% of patients. Infection developed
      in 27% of patients who underwent diversion vs 29% in patients who did not. In the
      present series, only mechanical instability was determined by stepwise logistic
      regression to be significantly associated with pelvic infection. This association
      was not altered by diversion status. CONCLUSIONS: Diversion of the fecal stream
      to protect open pelvic fractures is not associated with a lower incidence of
      abdominopelvic infectious complications. Diversion may offer protection to a
      select group of patients with extensive soft tissue injury or posterior wounds.
      Mechanical instability was independently associated with infection.

PMID- 9517742
TI  - Sentinel lymphadenectomy in thyroid malignant neoplasms.
AB  - BACKGROUND: Lymph node metastases for well-differentiated thyroid cancer are
      associated with high recurrence rates. Surgical options consist of blind nodal
      sampling, "berry-picking" procedures, and modified radical neck dissections.
      Sentinel lymph node dissection (SLND) has been described by our institution for
      melanoma and breast cancer. We have investigated the feasibility of SLND for
      thyroid cancer. DESIGN: From August 1994 to October 1996 we investigated the
      technique of intraoperative lymphatic mapping and SLND in 17 patients undergoing
      surgical management of a suspicious thyroid nodule not accompanied by palpable
      cervical adenopathy. SETTING: Patients were referred from endocrinologists in
      community and academic practices. Procedures were performed in a community
      hospital. PATIENTS: There were 14 women and 3 men, ranging in age from 22 to 69
      years (median, 48 years). INTERVENTIONS: At surgery, we exposed the thyroid lobe
      and used a tuberculin syringe to inject 0.1 to 0.8 mL of 1.0% isosulfan blue dye
      (mean, 0.5 mL) directly into the thyroid mass. Within seconds the blue dye passed
      along the lymphatics to the sentinel lymph node, which was then excised. Nodes
      were examined by routine processing and keratin immunohistochemical analysis to
      detect micrometastasis. MAIN OUTCOME MEASURES: The feasibility of lymphatic
      mapping in determining primary drainage of suspicious thyroid nodules. RESULTS:
      Lymphatic mapping and SLND was followed by total thyroidectomy, except in 1
      patient who underwent lobectomy for benign disease. Of the 17 nodules, 12 were
      ultimately diagnosed as thyroid carcinoma, 3 were follicular adenomas, and 2 were
      colloid nodules. Tumor sizes ranged from 0.8 to 4.0 cm. Lymphatic mapping was
      unsuccessful in 2 patients, whose lymphatics mapped to the retrosternum. All of
      the sentinel lymph nodes were paratracheal except in 2 women who also had jugular
      nodes that stained blue. Five (42%) of the 12 tumor nodules were associated with
      positive sentinel lymph nodes. Central neck dissections were performed in 5
      patients; in 2 instances (17%), the sentinel node was the only tumor-bearing
      lymph node. CONCLUSIONS: This is the first report of SLND for thyroid carcinoma.
      Our preliminary findings indicate that SLND can detect nonpalpable nodal
      metastasis with the same ease as in melanoma and breast cancer. The clinical
      significance of this technique in thyroid cancer remains to be determined.

PMID- 9517743
TI  - Endoscopic retrograde cholangiopancreatography and endoscopic endoprosthesis
      insertion in patients with Klatskin tumors.
AB  - OBJECTIVE: To assess the value and the associated morbidity of endoscopic
      retrograde cholangiopancreatography (ERCP) and endoscopic endoprosthesis
      insertion in the treatment of patients with Klatskin tumors. DESIGN:
      Retrospective study. SETTING: A tertiary referral center. PATIENTS: Fifty-five
      consecutive patients with Klatskin tumors diagnosed through typical
      cholangiographic and computed tomographic findings. INTERVENTION: Standard ERCP
      with endoscopic stenting technique was employed. Once the diagnosis of Klatskin
      tumor was confirmed on cholangiogram, endoscopic stenting was performed to bypass
      the stricture. Multiple stents were inserted if necessary to ensure adequate
      biliary drainage. MAIN OUTCOME MEASURES: The success rate of ERCP and endoscopic
      endoprosthesis insertion, successful drainage rate, early complications of
      endoscopic procedure, procedure-related mortality, and long-term outcome of
      endoprosthesis. RESULTS: Of the 55 patients, cholangiography was performed in 53
      (96%). In the 49 patients in whom endoscopic stenting was attempted, the
      procedure was successful in 28 patients (57%) at the first attempt and 8 patients
      (16%) at the second attempt, resulting in a cumulative success rate of 73%. Only
      20 of these patients had satisfactory biliary drainage, resulting in an overall
      successful drainage rate of 41%. Early complications, including acute
      cholangitis, acute pancreatitis, and postpapillotomy bleeding occurred in 14
      patients (25%). Three patients (5%) died of procedure-related complications. The
      median patency of the first endoprosthesis inserted was 1 week (range, 0-8 wk).
      The 30-day mortality rate was 18%. CONCLUSIONS: In patients with Klatskin tumors,
      ERCP and endoscopic endoprosthesis insertion have a low successful drainage rate,
      are associated with high morbidity and procedure-related mortality, and have a
      limited effect on long-term palliation. Endoscopic retrograde
      cholangiopancreatography and endoscopic endoprosthesis insertion have a limited
      value in the management of patients with Klatskin tumors.

PMID- 9517744
TI  - Embryologic bases of extended radical resection in pancreatic cancer.
AB  - OBJECTIVE: To analyze whether an embryologic "rationale" exists to the clinical
      and anatomicopathological data that suggest the execution of extended resections
      in patients with pancreatic cancer. METHODS: Reconstruction of serial
      histological sections of 18 human embryos and fetuses regarding the pancreatic
      region; anatomical microdissections of two 9-month fetuses. RESULTS: The ventral
      and dorsal pancreatic buds can be identified until the eighth week of
      development. A close developmental relationship between the dorsal pancreas and
      the lymphatic and nervous structures in the dorsal mesogastrium is observed.
      Other lymphatic stations are exclusively related to the ventral pancreas. The
      posterior fusion of the dorsal mesogastrium is a late event in embryologic
      development. CONCLUSIONS: The complete fusion of the 2 pancreatic buds occurs
      later than previously reported in the literature. The close embryologic relations
      of these buds with the lymphatic and nervous peripancreatic structures may
      support the need for extended resections in patients with pancreatic cancer.

PMID- 9517745
TI  - Risk factors for hyperamylasemia after hepatectomy using the Pringle maneuver:
      randomized analysis of surgical parameters.
AB  - OBJECTIVES: To determine whether the increased portal venous pressure caused by
      use of the Pringle maneuver contributes to inducing posthepatectomy
      hyperamylasemia and, subsequently, to evaluate risk factors for its development.
      DESIGN: Randomized study. SETTING: University hospital. PATIENTS: Forty patients
      who were going to undergo hepatectomy were assigned prospectively to either a
      superior mesenteric artery clamp (n=20) or a nonclamp (n=20) group by the random
      block method. INTERVENTIONS: The Pringle maneuver was used during hepatectomy,
      and in the superior mesenteric artery clamp group the superior mesenteric
      arteries were clamped simultaneously. MAIN OUTCOME MEASURES: Amylase activity,
      isozyme, and creatinine levels in the blood and urine samples were measured
      before and after surgery, and the amylase creatinine clearance ratio was
      estimated. RESULTS: The serum amylase activity levels of the superior mesenteric
      artery clamp and nonclamp groups did not differ significantly during the 7
      postoperative days. The serum amylase activity levels exceeded 250 U/L in 14
      patients (group 1) and remained below this level in 26 (group 2). The salivary
      type isozyme levels of group 1 increased significantly compared with those of
      group 2, and the levels of group 2 remained normal. The total amount of amylase
      excreted in the urine samples of group 1 patients also increased significantly,
      with the salivary-type isozyme predominating. All the mean amylase creatinine
      clearance ratios before and after surgery remained normal. The mode chi2 of the
      logistic model including the indocyanine green retention rate at 15 minutes and
      the ratio of the resected liver weight to the whole liver volume showed a
      significantly increased risk (P=.01). CONCLUSION: It is not the increased portal
      venous pressure caused by use of the Pringle maneuver but the liver function and
      the extent of liver resection that are considered risk factors for inducing
      posthepatectomy salivary-type hyperamylasemia.

PMID- 9517746
TI  - Prophylactic abdominal drainage after elective colonic resection and
      suprapromontory anastomosis: a multicenter study controlled by randomization.
      French Associations for Surgical Research.
AB  - BACKGROUND: Only 4 controlled trials have investigated whether prophylactic
      abdominal drainage was of value after colonic resection. None have been able to
      find any statistically significant difference, but the number of patients was
      small and the beta error risk was high. OBJECTIVES: To compare patients who
      underwent abdominal drainage with those who did not for the rate and severity of
      complications after elective colonic resection followed immediately by
      anastomosis of the suprapromontory colon and to compare suction drains with
      nonsuction drains. PATIENTS: Between September 1990 and June 1995, 319 patients
      (135 men and 184 women), whose mean age was 67 years (range, 22-95 years), with
      carcinoma, benign tumors, or colitis, located anywhere between the ascending and
      sigmoid colons, were included in the study. Patients were comparable for
      demographic characteristics, except that there were more patients with ascites in
      the group that did not undergo abdominal drainage (P<.02). INTERVENTIONS: After 2
      protocol violations, 156 patients were randomized to the abdominal drainage group
      and 161 to the no abdominal drainage group. All 317 anastomoses were tested for
      airtightness intraoperatively and repaired if leakage was found (n=71), and all
      patients with anastomoses received a routine diatrizoate sodium enema to detect
      infraclinical leakage. MAIN OUTCOME MEASURES: The postoperative complications
      possibly influenced by drainage included (1) deep complications for which
      drainage can lead to early diagnosis, such as generalized or localized
      peritonitis, intraabdominal hemorrhage, or hematoma; (2) complications believed
      to be enhanced by drainage, such as an operative wound (an abscess, disruption,
      or incisional hernia) or pulmonary (microatelectasis) and intestinal
      obstructions; and (3) complications directly due to the drains, such as
      ulcerations leading to fistulae, hemorrhages, drainage tract infections,
      difficulty in removal, intra-abdominal retention, and incisional disruptions.
      Subsidiary end points were the severity of these complications as assessed by the
      number of related subsequent operations and deaths. RESULTS: Twenty-six patients
      overall (8%) had postoperative complications possibly influenced by drainage (9%
      in the group that underwent abdominal drainage and 8% in the group that did not).
      This difference was not statistically significant (P<.90). One patient had a
      fistula directly imputable to drainage. There was no difference between suction
      and nonsuction drainage (P<.90). CONCLUSIONS: Routine abdominal drainage after
      colonic resection and immediate anastomosis decreases neither the rate nor the
      severity of anastomotic leakage. It can, occasionally, be detrimental.

PMID- 9517747
TI  - Quality of life in patients with cancer of the esophagus and gastric cardia: a
      case for palliative resection.
AB  - OBJECTIVE: To evaluate quality-of-life (QOL) parameters in patients undergoing
      esophagectomy, curative or palliative, for carcinoma. DESIGN: Nonconsecutive case
      series. PATIENTS: Eighty-eight patients who underwent esophagectomy for cancer
      (curative, n=49 [56%]; palliative, n=39 [44%]) provided QOL assessments over an
      18-month period. SETTING: Procedures for referral care were performed by a single
      team of clinicians in a tertiary referral center. Evaluations of QOL were made by
      1 independent trained investigator. OUTCOME MEASURES: Data were documented by
      questionnaire at interview and parameters evaluated included an esophageal module
      for the type and quantity of food intake, severity of related symptoms on eating,
      Eastern Cooperative Oncology Groups (ECOG) performance status, sleep, pain,
      leisure activity, working capacity, outlook on life, general well-being, and
      support from family and friends. A summation of selected parameters was used to
      calculate a total score. RESULTS: Significant improvements were recorded in both
      the curative and palliative groups for at least 1 year following surgery in the
      type (P<.03) and quantity (P<.03) of food intake and severity of diet-related
      symptoms (P<.02), when compared with preoperative considerations. Findings were
      comparable between the groups with regard to dietary intake. Pain status and
      total scores were worse in the palliative group at 9 months postoperatively but
      no significant differences between the groups were evident at any time for sleep,
      leisure activity, and ECOG performance status. CONCLUSIONS: To our knowledge,
      there are no previous data regarding a comparison of QOL considerations in
      patients who have undergone either potentially curative or palliative
      esophagectomy for malignant disease. Data analysis revealed that palliative
      esophagectomy provided enhanced QOL with marked symptomatic benefits and
      enjoyment of daily living comparable to that observed following curative
      resection.

PMID- 9517748
TI  - Surgery in Sweden.
AB  - Sweden has 9 university and regional hospitals and about 75 county hospitals.
      These hospitals are funded by counties that directly tax their inhabitants. In
      addition, the university hospitals use state money for education and research.
      The private sector performing major surgical procedures is small but slowly
      increasing. Reorganizations and closings of smaller hospitals are continually
      occurring, and various organizational models are being tested. Surgical care for
      inpatients is free for Swedish citizens; however, there is a small fee for
      outpatient care (US $10-$20 per visit). Education in surgery is changing rapidly
      with the introduction of new methods. Clinical research closely connected to
      basic sciences will be of profound importance for future development. The present
      article is confined mainly to general surgery in Sweden, but it also covers some
      general aspects of medicine in Sweden.

PMID- 9517749
TI  - Middle segment pancreatectomy: a novel technique for conserving pancreatic
      tissue.
AB  - Pancreatoduodenectomy and extended distal pancreatectomy for benign tumors in the
      pancreatic neck and body incur a notable waste of normal tissue and unnecessary
      risk of both diabetes mellitus and splenic loss. We describe the technique of a
      limited resection of the middle portion of the pancreas, termed middle segment
      pancreatectomy, and report our results in 12 patients. Middle segment
      pancreatectomy was used in 12 consecutive patients with pancreatic tumors of the
      neck or body. The transected pancreatic head was sutured with duct ligation, and
      a Roux-en-Y loop of jejunum was anastomosed to the tail using mucosa-to-mucosa
      duct approximation and a 5F catheter for duct stenting and drainage. In 12
      patients, 7 with cystic tumors (5 patients with serous cystadenoma; 2 patients
      with mucinous cystic neoplasms), 3 with islet cell adenomas, 1 with islet cell
      carcinoma, and 1 with intraductal papillary mucinous tumor, the tumor was
      resected by a middle segment pancreatectomy. In each case, the tumor, measuring
      0.9 to 5.2 cm, lay in the neck or body of the pancreas and could not be safely
      enucleated without compromising the pancreatic duct. Each tumor was resected with
      clear margins. Two patients had a temporary pancreatic fistula; 1 patient had
      delayed gastric emptying. Median postoperative length of stay was 8 days. No
      patient became diabetic or required oral pancreatic enzyme supplements. No local
      recurrences occurred after a mean follow-up of 18 months. Middle segment
      pancreatectomy is a safe and effective technique for resecting selected
      pancreatic tumors in the neck and body of the pancreas while preserving
      pancreatic endocrine and exocrine function and the spleen.

PMID- 9517750
TI  - Systemic inflammatory response syndrome and magic bullets: finding the target and
      improving the aim.

PMID- 9517751
TI  - Gastric tonometry is easy and valuable.

PMID- 9517752
TI  - Adenoviral vector infection of the pancreas.

PMID- 9517753
TI  - George Tiemann and the American surgical instrument trade in the preantiseptic
      era.

PMID- 9517754
TI  - Single photon emission computed tomography scanning in neuropsychiatric systemic
      lupus erythematosus.

PMID- 9517755
TI  - Methotrexate induced lymphoma?

PMID- 9517756
TI  - Trends in antirheumatic medication use among patients with rheumatoid arthritis,
      1981-1996.
AB  - OBJECTIVE: To describe changes in antirheumatic medication use by patients with
      rheumatoid arthritis (RA) over the 15 years 1981 to 1996. METHODS: Medication use
      was ascertained every 6 months by mailed Health Assessment Questionnaire in a
      cohort of patients recruited from the local community (n = 305; mean duration of
      RA at study entry 14.2 yrs). Patients were treated by 53 rheumatologists and over
      200 other physicians during the study. The proportions of patients treated with
      nonsteroidal antiinflammatory drugs (NSAID), disease modifying antirheumatic
      drugs (DMARD), prednisone, intraarticular corticosteroids, and analgesics were
      determined in serial cross sectional analyses, and trends in medication use over
      time were analyzed using linear regression. RESULTS: From 1981 to 1996, the
      proportion of patients treated with DMARD increased from 32 to 47% (average
      increase 1.06% each year; p < 0.0001), while the proportion treated with NSAID
      decreased from 86 to 76% (average decrease 0.57% each year; p < 0.0001). The
      proportion of patients treated with prednisone remained between 30 and 40%, with
      a trend toward increasing use over time (average increase 0.2% each year; p =
      0.05). In contrast, the proportion treated with intraarticular corticosteroids
      decreased from 14.4 to 6.7% (average decrease 0.46% each year; p < 0.0001). In
      1996, the most prevalent patterns of medication use were the use of NSAID alone
      (24.4%), use of an NSAID and DMARD (16.3%), and use of an NSAID, DMARD, and
      prednisone (12.2%). Use of an NSAID as the only antirheumatic medication
      decreased over time, and the use of DMARD in combination with other medications
      increased. CONCLUSION: The proportion of patients with RA treated with DMARD
      increased substantially from 1981 to 1996. This change in practice occurred
      during the time in which the concept of inverting the traditional therapeutic
      pyramid became popular, and may reflect a translation among clinicians of the
      philosophy of "early DMARD use" to "consistent DMARD use," even among patients
      with RA of moderate or longstanding duration.

PMID- 9517757
TI  - Patterns of radiological progression in early rheumatoid arthritis: results of an
      8 year prospective study.
AB  - OBJECTIVE: To describe the course of radiological progression in a cohort of 126
      patients presenting with early nonerosive rheumatoid arthritis (RA). METHODS:
      Criteria for recruitment to the study were fulfillment of the 1958 American
      Rheumatism Association criteria, absence of erosive disease at presentation and
      duration of symptoms less than 3 years. Radiographs of hands and feet at 0, 1, 2,
      5, and 8 years were available on 114 patients and were scored by Sharp's method
      for erosion (ERO) and joint space narrowing (JSN). Eighty-six patients were typed
      for the RA susceptibility shared HLA-DR epitope. RESULTS: The feet showed
      greatest initial radiological progression, but tended to reach an earlier and
      lower plateau. ERO progressed more rapidly than JSN in the first 2 years, but in
      parallel thereafter. The relative proportion of ERO:JSN varied, 1:1 for the
      wrists, 4:1 for the proximal interphalangeal joints. Thirty-eight percent of
      joints were eroded at 2 years, 63% at 8 years. Four patterns of radiological
      progression were identified: flat or nonerosive disease in 29 patients, linear in
      51, lag in 13, and plateau in 19 (irregular in 2). Changes in the rate of
      radiological progression were reflected by the time-integrated C-reactive protein
      over the same period. Rheumatoid factor titer was higher in the progressive
      groups compared to the flat group (p = 0.01). The RA susceptibility shared HLA-DR
      epitope was more frequent in the linear compared to the flat group (p = 0.03).
      CONCLUSION: A large proportion of joints become eroded in the first 2 years of
      early RA. The subsequent course of radiological progression is highly variable
      and cannot be easily explained by any single model.

PMID- 9517758
TI  - Time lag between active joint inflammation and radiological progression in
      patients with early rheumatoid arthritis.
AB  - OBJECTIVE: To determine clinical variables useful in predicting the prognosis of
      patients with early rheumatoid arthritis (RA) by investigating the relationship
      between clinical variables and radiological progression. METHODS: One hundred
      eighteen patients with early RA whose symptoms developed within the previous year
      were enrolled in a prospective study. Data from the 98 patients who completed the
      2 year study were analyzed, using the number of erosive joints and Larsen's score
      as the outcome of RA. RESULTS: Increases in the number of erosive joints at 12
      months after entry into the study were significantly correlated with the number
      of swollen joints (r = 0.510), erythrocyte sedimentation rate (ESR) (r = 0.404),
      and C-reactive protein (CRP) (r = 0.487) at 6 months. The same results were seen
      using Larsen's score as the measure of outcome. The average number of erosive
      joints or mean Larsen's score at 12 months was higher in patients whose levels of
      CRP were high at 6 months and suppressed by 12 months, but increased much less in
      patients whose levels of CRP were successfully suppressed by 6 months. More joint
      erosions were noted in patients with positive rheumatoid factor (RF) than in RF
      negative patients. CONCLUSION: Joint erosions appeared with a certain time lag
      after active synovitis. Earlier introduction of effective treatment is
      recommended for the prevention of RA joint damage. The presence of RF, number of
      swollen joints, ESR, and levels of CRP at 6 months after starting therapy are the
      most useful variables to predict radiological progression in patients with early
      RA.

PMID- 9517759
TI  - Methotrexate and cyclooxygenase metabolism in cultured human rheumatoid
      synoviocytes.
AB  - OBJECTIVE: Our objective was to characterize the effect of methotrexate (MTX) on
      prostaglandin E2 (PGE2) synthesis in cultured human rheumatoid synovial cells.
      Prostaglandins (PG) are important mediators of inflammation and joint destruction
      in rheumatoid arthritis (RA). Two isoforms of cyclooxygenase (COX), the key
      enzyme in PG synthesis, have been characterized: a constitutively expressed form,
      COX-1, and an inducible form, COX-2. The mechanisms of action of low dose MTX in
      RA treatment are still poorly understood. As the clinical effects are often first
      noticed within a month of starting MTX therapy, an antiinflammatory action has
      been proposed. METHODS: Adherent synovial cells were obtained by collagenase
      digestion of rheumatoid synovium, isolated from patients with RA undergoing
      synovectomy. Between passages 3 and 6, cultured synovial cells were incubated
      with or without MTX for 54 h, at various concentrations. Interleukin (IL)-1beta
      (1 ng/ml) was added or not for the last 6 h of incubation. Supernatants were
      harvested and assayed for PGE2 by enzyme immunoassay (EIA). Exogenous [1
      14C]arachidonic acid metabolism of synoviocytes was analyzed by reverse phase
      high performance liquid chromatography (RP-HPLC). COX-1 and COX-2 mRNA expression
      was determined by total RNA extraction and reverse transcription polymerase chain
      reaction. RESULTS: Cellular viability was not affected by MTX. EIA showed that
      MTX decreased IL-1beta induced PGE2 production by synoviocytes in a dose
      dependent manner. RP-HPLC analysis confirmed the inhibition of PGE2 and (12S)-12
      hydroxy-5,8,10-heptadecatrienoic acid production. COX-1 and IL-1beta induced COX
      2 mRNA expression were not inhibited by MTX. CONCLUSION: MTX has an inhibitory
      effect on IL-1beta stimulated production of PGE2 by cultured human rheumatoid
      synoviocytes, without affecting either COX mRNA expression. Among various
      biochemical and immunologic events, MTX could have an antiinflammatory action by
      decreasing PGE2 release.

PMID- 9517760
TI  - Folic acid supplementation prevents deficient blood folate levels and
      hyperhomocysteinemia during longterm, low dose methotrexate therapy for
      rheumatoid arthritis: implications for cardiovascular disease prevention.
AB  - OBJECTIVE: To determine the effect of longterm methotrexate (MTX) therapy and
      folic acid supplementation on folate nutriture and homocysteine levels in
      patients with rheumatoid arthritis. METHODS: A double blind, placebo controlled
      trial lasting one year was conducted at one academic medical center. A total of
      79 patients taking low dose MTX were followed up to one year. The patients were
      randomized to receive placebo or 5 or 27.5 mg folic acid supplementation per
      week. RESULTS: Plasma and erythrocyte folate levels and plasma homocysteine
      levels were determined. The folate nutriture of patients taking low dose MTX
      declined without folic acid supplementation. Plasma homocysteine levels increased
      significantly over a one year period in the placebo group. Low folate nutriture
      and hyperhomocysteinemia occurred with greater frequency in the placebo group
      than in the folic acid supplemented groups. CONCLUSION: For longterm, low dose
      MTX therapy, there are now at least 3 reasons to consider supplementation with
      folic acid (a low cost prescription): (1) to prevent MTX toxicity, (2) to prevent
      or treat folate deficiency, and (3) to prevent hyperhomocysteinemia, considered
      by many investigators to be a risk factor for cardiovascular disease.

PMID- 9517761
TI  - Dispersion of ventricular repolarization: a new marker of ventricular arrhythmias
      in patients with rheumatoid arthritis.
AB  - OBJECTIVE: To determine the value of dispersion of ventricular repolarization as
      a diagnostic tool to assess the risk for ventricular arrhythmias in patients with
      rheumatoid arthritis (RA). METHODS: We examined 42 patients with RA (age 44+/-4.8
      yrs; 32 women and 10 men) and 42 age matched healthy subjects as the control
      group. Repolarization dispersion variables were calculated based on the
      difference between maximal and minimal values of QT, QTc, JT, and JTc (QTd, QTc
      d, JTd, and JTc-d, respectively) from 12 lead electrocardiographic (ECG)
      recording at 50 mm/s. The frequency of ventricular arrhythmias by means of 24 h
      ambulatory ECG monitoring was investigated. A grade of > 3 ventricular
      arrhythmias according to modified Lown and Wolf classification was accepted as
      complex arrhythmias. RESULTS: We found QT and QTc intervals 392+/-20 and 409+/-38
      ms in patients; values in controls were 387+/-22 and 400+/-14 ms, respectively; p
      > 0.05. QTd, QTc-d, JTd, and JTc-d intervals were 61.6+/-1.6, 77.6+/-1.1, 72.5+/
      1.8, and 93.3+/-1.5 ms in patients and 40.3+/-0.9, 55+/-1.2, 42.6+/-0.4, and
      52.9+/-0.8 ms in controls, respectively; p < 0.001. Thirty-two of the patients
      had complex premature ventricular complexes during 24 h ECG and the prevalence of
      premature ventricular complexes was found to be higher than in controls (p <
      0.001). No correlation was found between complex premature ventricular complexes
      and QT, but there was a correlation between complex premature ventricular
      complexes and dispersion variables in patients with RA. CONCLUSION: Striking
      increases in QT dispersion indicating regional inhomogeneity of ventricular
      repolarization were noted in patients with RA. QT dispersion might be a useful
      marker of cardiovascular morbidity and mortality due to complex ventricular
      arrhythmias in patients with RA.

PMID- 9517762
TI  - Total wrist arthroplasty: a quantitative review of the last 30 years.
AB  - OBJECTIVE: To investigate the suitability of design of 3 generations of wrist
      prostheses. METHODS: A comparative review was performed on the Swanson, Volz,
      Meuli, Trispherical, Biaxial, and MWP III total wrist prostheses. RESULTS: The
      review revealed a sharp rise in fracture and revision rates for the Swanson
      prosthesis after 55 months followup, with the most likely site for fracture at
      the junction of the distal stem and barrel. The Volz prosthesis had initial
      problems with a postoperative resting stance of ulnar deviation, due to the
      radial shift of the axis of the prosthesis to that of the normal wrist. A
      modified prosthesis corrected the problem of ulnar deviation; however, problems
      with bone resorption under the collar of the radial component and metacarpal
      loosening were seen. The majority of complications occurred in patients with post
      traumatic degenerative joint disease. The remaining prostheses have had only a
      few clinical studies, and are presented to illustrate the different design
      concepts adopted. CONCLUSION: Total wrist arthroplasty has less satisfactory
      clinical outcomes compared to hip and knee arthroplasty. The changes in design
      from the first to the third generation, with closer approximation to the wrist
      joint's center of rotation, have led to encouraging results. The comparison of
      the clinical outcome of different prostheses has been difficult due to the lack
      of uniformity of outcome measures used.

PMID- 9517763
TI  - Destruction and reconstruction of hand joints in rheumatoid arthritis. A 20 year
      followup study.
AB  - OBJECTIVE: To examine the radiographic endpoint changes and performed joint
      fusions and arthroplasties in hand joints in rheumatoid arthritis (RA) occurring
      over a 20 year period. METHODS: In 83 patients with recent (< 6 months)
      rheumatoid factor positive RA, radiographs were taken at 15 and 20 years from
      entry. The Larsen grades for 12 hand joints were evaluated, as well as the
      preoperative grades for reconstructed joints. Data of the performed hand joint
      fusions and arthroplasties were obtained. RESULTS: At 15 year followup the mean
      Larsen grade of wrist joints was 2.5, metacarpophalangeal (MCP) I-V 1.0-1.8, and
      interphalangeal I and proximal interphalangeal (PIP) II-V 0.7-0.9. At the
      endpoint the mean grades were: wrist joint 2.7, MCP I 1.1, MCP II 2.2, MCP III
      1.9, MCP IV 1.3, MCP V 1.5, IP I and PIP II-V 0.7-1.0. Modified Larsen grade for
      carpometacarpal I was 1.6 and 2.0 at 15 year followup and endpoint, respectively.
      Reconstructive surgery was performed in 33/83 patients. The number of operations
      was 83, and 38 of them were wrist fusions. CONCLUSION: In this inception cohort,
      wrist joints had the highest destruction and the need for reconstructive surgery;
      the grade of destruction was lower in MCP and PIP joints, in this order.
      Possibilities of reconstructive surgery are discussed.

PMID- 9517764
TI  - Antiendothelial cell antibodies in scleroderma correlate with severe digital
      ischemia and pulmonary arterial hypertension.
AB  - OBJECTIVE: To determine the prevalence of IgG antiendothelial cell antibodies
      (AECA) in patients with scleroderma (systemic sclerosis, SSc) and to correlate it
      with clinical spectrum and autoantibody profile. METHODS: Seventy-six patients
      with SSc and 50 matched healthy controls were studied. Immunological variables
      were antinuclear antibody (ANA), rheumatoid factor (RF), and Scl-70. IgG-AECA was
      measured by cellular ELISA. RESULTS: The prevalence of IgG-AECA was 27.6% in
      patients with SSc compared to 6% in controls (p < 0.01). Forty percent of
      patients with diffuse disease had this antibody, versus 13.5% of those with
      limited cutaneous involvement (p < 0.05). Patients with AECA had significantly
      higher incidence of digital infarcts and gangrene (p < 0.01) and pulmonary
      arterial hypertension (p < 0.001) than those without. In the AECA positive group,
      mean IgG-AECA levels (measured by absorbance values) were significantly higher in
      patients with digital infarcts (0.91+/-0.31 vs 0.60+/-0.05; p < 0.01) and
      pulmonary arterial hypertension (1.14+/-0.37 vs 0.68+/-0.13; p < 0.001) compared
      to those without these features. CONCLUSION: IgG-AECA appears to be an important
      marker for disease severity in scleroderma.

PMID- 9517765
TI  - Acute transverse myelopathy in systemic lupus erythematosus: clinical
      presentation, treatment, and outcome.
AB  - OBJECTIVE: Acute transverse myelopathy (ATM) is a rare manifestation of systemic
      lupus erythematosus (SLE). The pathogenesis is unclear and the optimal management
      strategy is uncertain because of the lack of controlled trials. In this study,
      the clinical presentation, autoantibody profile, treatment, and outcome of cases
      of ATM in our local SLE population were retrospectively analyzed and compared
      with SLE controls. RESULTS: Ten cases of ATM were identified among 315 patients
      with SLE studied, giving a prevalence of 3.2%. In 5 of the patients, ATM was the
      initial manifestation of SLE. The cervical cord was the most common site of
      involvement (50%). Cerebrospinal fluid abnormalities were present in 63% of the
      patients, while magnetic resonance imaging (MRI) of the spinal cord revealed
      abnormal T2 signals in 56%. Only one patient had lupus nephritis. ATM was not
      associated with antiribosomal P or anti-extractable nuclear antigen (anti-ENA)
      antibodies. Positive dsDNA antibody was present in 40% of the ATM cases, which
      was significantly lower than that of patients with active SLE without spinal cord
      disease (75%; p = 0.04). No significant differences in the prevalence of
      anticardiolipin antibodies and lupus anticoagulant between the ATM and the non
      ATM group were observed. Only 3 patients with ATM showed hypocomplementemia or
      disease activity in other organs at the time of diagnosis. All the patients with
      ATM received corticosteroids, while 9 were given cytotoxic agents in addition.
      The response to treatment was variable -- 40% of patients had complete motor and
      sphincter recovery and 30% had mild residual spasticity of the lower limbs.
      CONCLUSION: In our SLE population, ATM was not associated with antiribosomal P,
      anti-ENA, or antiphospholipid antibodies. Systemic complement activation was not
      evident in most patients during the acute phase of myelitis. Early aggressive
      therapy using a combination of corticosteroid and cytotoxic agents is associated
      with a satisfactory outcome. Further prospective study is needed to delineate the
      best treatment and its efficacy in the prevention of relapses.

PMID- 9517766
TI  - Epitope mapping of human centromere autoantigen centromere protein C (CENP-C);
      heterogeneity of anti-CENP-C response in rheumatic diseases.
AB  - OBJECTIVE: To analyze the autoantigenic epitopes of centromere protein C (CENP-C)
      recognized by anti-centromere antibodies (ACA). METHODS: A series of truncated
      peptides of human CENP-C were expressed in Escherichia coli and immunoblotting
      analysis was performed with 45 ACA positive sera obtained from patients with
      different types of autoimmune diseases. RESULTS: Although 9 epitopes were
      scattered over the entire molecule, the N terminus was immunodominant for IgG and
      IgM classes and the C terminus was dominant for IgG class. Both epitopes were
      separately located within the instability and centromere targeting domains in
      vivo, or the oligomerization-accessible and homodimerization domains in vitro,
      respectively. In contrast, minor epitopes were clustered at the internal DNA
      binding domain. A number of patterns of immunoreactivities against 3
      representative antigenic sites by IgG or IgM class antibodies were found.
      CONCLUSION: The results indicated the existence of different anti-CENP-C
      responses in rheumatic diseases and a possible correlation between antigenic
      regions and functional sites in the CENP-C antigen.

PMID- 9517767
TI  - The role of the clinical rheumatologist in the establishment of a large sibling
      pair resource for systemic lupus erythematosus.
AB  - OBJECTIVE: To recruit a large cohort of sibling pairs with systemic lupus
      erythematosus (SLE) as a clinical and biologic resource for genetic studies in
      SLE. METHODS: Complementary approaches were used to identify suitable families.
      The study was advertised in the newsletters of the Lupus Foundation of America
      and the Arthritis Foundation. Fliers were mailed to 250 clinical rheumatologists
      across the US, as well as to the local branches of the Lupus Foundation. All
      advertisements displayed a toll-free telephone number for interested patients to
      contact our group. Patients were then screened in a telephone interview by a
      university rheumatologist and their diagnosis was subsequently verified by
      telephone with the treating physician. Retrospective review of medical records
      was used to confirm the accuracy of the clinical data obtained by telephone
      interview. RESULTS: About 1400 subjects were screened by telephone over a 3 year
      period. After interviews with subjects and their physicians, 179 families were
      recruited in which at least 2 siblings have definite SLE. Based on the telephone
      interviews, a detailed clinical, demographic, and family history database was
      established for all patients in the study. Over 80% of the study subjects receive
      their SLE care from rheumatologists in clinical practice. CONCLUSION: We found
      that rheumatologists were reliable in confirming or excluding the diagnosis of
      SLE by telephone. Targeted patient advertising followed by physician-to-physician
      interviews is a time efficient and accurate method for recruiting patients with
      SLE for large genetic studies and may be applicable to the study of other
      rheumatologic conditions.

PMID- 9517768
TI  - Prevalence of symptoms of dry mouth and their relationship to saliva production
      in community dwelling elderly: the SEE project. Salisbury Eye Evaluation.
AB  - OBJECTIVE: To estimate the prevalence of dry mouth symptoms and their correlation
      with saliva production in a population based sample of elderly people in the
      United States. METHODS: Two dry mouth questions were administered to and a
      modified Saxon test was performed in participants in a population based
      prevalence survey conducted among 2520 noninstitutionalized community dwelling
      residents of Salisbury, Maryland, aged 65-84 years. RESULTS: Seventeen percent
      reported having either dryness of mouth or waking at night feeling dryness in the
      mouth and needing to drink fluids often or all the time; 10.7% noted the former
      and 11.5% the latter. The prevalence of dry mouth symptoms increased with
      increasing age, was greater in women than men, and was greater in whites than
      blacks. The mean (SD) amount of saliva production was 2.38 (1.00) g/min; mean
      saliva production decreased with increasing age and was lower in women than men;
      no difference was noted by race. Persons with dry mouth symptom either often or
      all the time had significantly lower salivary production, even after adjustment
      for age and sex. CONCLUSION: Symptoms of dry mouth are common in the community
      dwelling elderly population, especially in white women, and correlate with
      decreased salivary production.

PMID- 9517769
TI  - Induction of remission in Wegener's granulomatosis with low dose methotrexate.
AB  - OBJECTIVE: To study the efficacy of methotrexate (MTX) plus low dose
      corticosteroids for induction of remission in generalized Wegener's
      granulomatosis (WG) and to possibly identify predictive factors for the outcome
      under this therapy. METHODS: We conducted a prospective, open label study,
      including 17 patients with not immediately life threatening, generalized WG.
      Treatment consisted of intravenous MTX 0.3 mg/kg once weekly plus daily oral low
      dose prednisone for initial diagnosis of WG in 11 and for a generalized relapse
      of WG in 6 patients. Interdisciplinary, standardized assessments of disease
      activity and extent were done 3-monthly. RESULTS: Within a median treatment
      period of 24.5 months remission could be achieved in 10/17 patients (59%), their
      median corticosteroid dose during that time was 1.75 mg/day. Seven patients with
      a median concomitant prednisone dose of 7.5 mg/day did not respond, among them 4
      patients who were treated for a relapse of WG. Signs of de novo
      glomerulonephritis occurred in 5 of the 7 nonresponders. Significant side
      effects, including opportunistic infections, did not occur. CONCLUSION: Weekly
      low dose MTX in combination with low dose corticosteroids leads to an acceptable
      remission rate of almost 60% without significant side effects. Patients treated
      for a relapse of WG and patients with a need for a higher concomitant prednisone
      dose seem to be at risk for nonresponse, with a high likelihood of developing de
      novo glomerulonephritis.

PMID- 9517770
TI  - Factor V Leiden mutation in patients with Behcet's disease.
AB  - OBJECTIVE: To determine the relation between factor V Leiden and Behcet's disease
      (BD), which is described as chronic relapsing vasculitis with pathogenetic
      mechanisms that seem to be related to anticoagulant pathways. METHODS: Using
      polymerase chain reaction, the factor V Leiden mutation was investigated in 44
      patients with BD, of which 5 had thrombotic histories. RESULTS: Ten patients were
      found to have the factor V Leiden mutation. This frequency (22.7%) was higher
      than that of our general population (7.1 %) (p < 0.05). Of the 5 patients with BD
      with thrombotic histories, 3 (60%) had factor V Leiden mutation (one homozygote,
      2 heterozygote), while 7 of 39 (17.9%) patients with no thrombotic history had
      the factor V Leiden mutation (2 homozygotes, 5 heterozygotes). There is no
      statistical difference in the frequency of the factor V mutation between patients
      with BD with no thrombosis and the control group. The frequency of thrombosis in
      BD with and without factor V Leiden mutation was (3/10) 30% and (2/34) 5.9%,
      respectively. CONCLUSION: These findings suggest that homozygosity or
      heterozygosity for factor V Leiden is not always associated with occurrence of
      venous thrombosis in BD, but it may be a contributing risk factor for venous
      thromboembolic events in these patients.

PMID- 9517771
TI  - Intercellular adhesion molecule-1 expression in adjuvant arthritis in rats:
      inhibition by kappa-opioid agonist but not by NSAID.
AB  - OBJECTIVE: To quantify intercellular adhesion molecule-1 (ICAM-1) expression in
      normal and adjuvant arthritic rats and to determine the extent to which ICAM-1
      expression in arthritic animals is altered by treatment with a prototype
      nonsteroidal antiinflammatory drug (NSAID) and a kappa-opioid agonist. METHODS:
      Unilateral hind paw inflammation was induced by intradermal injection of Freund's
      complete adjuvant (FCA) into the right hind paw of female Lewis rats.
      Polyarthritis was induced by intradermal injection of FCA into the base of the
      tail of female dark Agouti rats. The NSAID naproxen [5 mg/kg intraperitoneally
      (ip)] or the kappa-opioid PD117302 (15 mg/kg ip) was administered twice daily
      throughout the experiment (21 days). ICAM-1 expression was quantified using
      monoclonal antibodies against rat ICAM-1 that bind to the endothelium in
      proportion to the degree of adhesion molecule expression. RESULTS: ICAM-1
      expression was significantly upregulated in the joints of affected limbs of
      animals with both unilateral hind paw inflammation and polyarthritis. In animals
      treated with PD 117302 and naproxen there was a significant attenuation of
      arthritis; however, only treatment with PD117302 was able to significantly
      inhibit the upregulation of ICAM-1 expression in arthritic joints. CONCLUSION:
      ICAM-1 expression is upregulated in experimental arthritis. It appears that the
      kappa-opioid PD117302, but not the NSAID naproxen, inhibits the upregulation of
      ICAM-1 in arthritic joints, suggesting these agents act via different mechanisms.
      The ability of the kappa-agonist, PD117302, to inhibit both the inflammation and
      upregulation of ICAM-1 in arthritic joints emphasizes the potential of kappa
      agonists as antiarthritic agents.

PMID- 9517772
TI  - Relative increase of biglycan and decorin and altered chondroitin sulfate
      epitopes in the degenerating human intervertebral disc.
AB  - OBJECTIVE: Proteoglycans are major components of the extracellular matrix of the
      intervertebral disc. They are vital for the biomechanical properties of the
      tissue, and are subject to changes in disc degeneration. We aimed to further
      define these changes and their relationship to normal aging. METHODS: Normal
      discs (age 13-53 years, n = 6) were analyzed from 5 different sites across the
      sagittal anterior-posterior direction. Degenerated anterior annulus fibrosus was
      collected from 7 patients aged 39-46 years. Extracted proteoglycans were
      separated using agarose and polyacrylamide gel electrophoresis and detected with
      toluidine blue staining and Western blotting. RESULTS: The center of the disc
      showed the highest level of total proteoglycans, but lowest levels of decorin and
      biglycan. Western blots displayed reduced signal for both glycanated and
      nonglycanated biglycan and decorin after adolescence, while an increased signal
      of biglycan was observed in degenerated annuli. The 7D4(-) and 3B3(-) epitopes on
      native chondroitin sulfate chains were present in the large proteoglycans of
      intervertebral discs, but their signal intensity had no correlation to
      degeneration. Chondroitinase ABC digestion of the blots brought up 7D4(+) signal
      in the small proteoglycans of degenerated, but not in healthy tissue. Decrease or
      total loss of 2B6(+) epitope (indicating 4-sulfated stubs of chondroitin sulfate
      chains) were found in the large proteoglycans of all degenerated annuli.
      CONCLUSION: Human intervertebral disc degeneration involves the accumulation of
      decorin and biglycan relative to other uronic acid containing proteoglycans, the
      disappearance of 4-sulfated core region in aggrecan-like large proteoglycans, and
      the emergence of a core structure in the chains of small proteoglycans reacting
      with the 7D4 antibody; these findings indicate a fundamental alteration in matrix
      properties that may contribute to the pathogenesis of the disease.

PMID- 9517773
TI  - Beneficial effects of intermittent fluid pressure of low physiological magnitude
      on cartilage and inflammation in osteoarthritis. An in vitro study.
AB  - OBJECTIVE: To investigate the in vitro effects of low physiological levels of
      intermittent fluid pressure (0-13 kPa; 0.33 Hz), in the absence of mechanical
      stress, on articular cartilage, inflammatory cells, and on the combination of
      these components, present in the osteoarthritic (OA) joint. METHODS: Normal and
      OA cartilage was obtained at autopsy. Mononuclear cells (MNC) were isolated from
      synovial fluid of patients with osteoarthritis (OA-SF) or peripheral blood from
      healthy donors (PB). Cartilage and MNC were cultured alone and in co-culture;
      cultures were carried out with and without exposure to intermittent fluid
      pressure. Levels of intermittent fluid pressure varied from 0 to 13 kPa (0.33
      Hz), comparable with levels present during joint distraction in treatment of OA.
      Changes in cartilage proteoglycan metabolism and MNC cytokine production were
      analyzed. RESULTS: Cartilage matrix synthesis was stimulated by intermittent
      fluid pressure in OA cartilage, while normal cartilage was not affected. No
      effects on proteoglycan release were detected. Inhibition of cartilage
      proteoglycan synthesis, induced by OA synovial fluid MNC (OA-SF-MNC) in co
      culture, was reduced when cultures had been exposed to intermittent fluid
      pressure. Analysis of conditioned media of OA-SF-MNC revealed that the beneficial
      effect of intermittent fluid pressure was accompanied by a decrease in production
      of the catabolic cytokines interleukin 1 and tumor necrosis factor-alpha. Similar
      effects were observed for MNC isolated from PB. CONCLUSION: Low levels of
      intermittent fluid pressure, as occur in vivo during joint distraction, have
      beneficial effects on joint tissue in OA, indicating that this factor could be
      useful in treatment of OA.

PMID- 9517774
TI  - Regional differences in the rise in blood levels of antigenic keratan sulfate and
      hyaluronan after chymopapain induced knee joint injury.
AB  - OBJECTIVE: Results from several recent studies suggest that the levels of
      antigenic keratan sulfate (agKS) and hyaluronan (HA) in serum provide useful
      information about changes taking place in injured or diseased synovial joints. To
      improve our understanding of the significance of such changes, we investigated
      the points of entry of these molecules into the blood circulation and their
      subsequent clearance after experimentally induced injury to rabbit knee joint.
      METHODS: Chymopapain was injected into knee joints of 8 young adult rabbits to
      induce aggrecan degradation in articular cartilage within the injected joint.
      Levels of agKS and HA in serum from various blood vessels were measured before
      and 5 h after the injury. The statistical significance of injury related changes
      and differences among the different vessels were evaluated. RESULTS: After the
      injury, the level of agKS rose most significantly in the popliteal vein draining
      the injected knee joint and dropped rapidly by the time the blood reached the
      femoral vein. The level of agKS was similar, although lower, in other blood
      vessels but, in each case, it was significantly higher than before the injection.
      The level of HA showed a different pattern of changes after injection. While
      highest in the popliteal vein draining the injected knee, HA was markedly
      elevated in the cranial vena cava, close to the entry of lymph into the
      circulation, and was 50% lower in the hepatic than in the portal vein.
      CONCLUSION: (1) Measurement of agKS and HA in a blood vessel draining or close to
      an injured/diseased knee joint may provide more specific information about
      degradative changes taking place in that joint than measurement of levels of
      these markers in other blood vessels; (2) some HA molecules but no measurable
      amounts of agKS enter the blood circulation via the lymphatic system: and (3) HA
      but not agKS is very rapidly cleared from the blood by the liver.

PMID- 9517775
TI  - Synovial fluid cartilage metabolism marker concentrations in osteonecrosis of the
      femoral head compared with osteoarthrosis of the hip.
AB  - OBJECTIVE: Biochemical aspects of the etiology of articular cartilage
      degeneration in osteonecrosis of the femoral head have not been investigated
      extensively. We analyzed biochemical conditions in the hip joint cavity,
      regarding articular cartilage turnover in osteonecrosis of the femoral head
      (ONFH). METHODS: Cartilage metabolism markers in synovial fluid were measured.
      Synovial fluid (SF) samples were collected from 19 ONFH cases and 17 control hips
      with osteoarthrosis (OA). Concentrations of carboxy-terminal type II procollagen
      peptide (pCOL-II-C), matrix metalloproteinase-3 (MMP-3), and tissue inhibitor of
      metalloproteinase-1 (TIMP-1) were measured. In addition, concentrations of
      unsaturated disaccharides of hyaluronic acid (delta di-HA), chondroitin 4-sulfate
      (delta di-4S), and chondroitin 6-sulfate (delta di-6S) in SF were measured by
      high performance liquid chromatography. RESULTS: The mean SF concentration of
      pCOL-II-C was higher on ONFH than in OA. The mean SF MMP-3 level was higher in
      ONFH than in OA, while the mean SF TIMP-1 level was the same in the 2 groups. The
      SF concentration of delta di-HA and the delta di-6S/delta di-4S ratio were higher
      in ONFH than in OA. CONCLUSION: Higher concentrations of cartilage metabolism
      markers in ONFH compared with OA SF suggest elevated cartilage turnover in the
      former disease.

PMID- 9517776
TI  - Oral administration of doxycycline reduces collagenase and gelatinase activities
      in extracts of human osteoarthritic cartilage.
AB  - OBJECTIVE: To determine whether oral administration of doxycycline in clinically
      relevant doses will suppress activities of collagenase and gelatinase in extracts
      of human osteoarthritic (OA) cartilage. METHODS: Femoral heads were obtained from
      21 patients undergoing arthroplasty for endstage hip OA. Activities of
      collagenase and gelatinase were measured in extracts of the OA cartilage from
      patients who received doxycycline, 100 mg bid or qam for 5 days before surgery (n
      = 5 and n = 6, respectively), 200 mg as a single dose 3 days before surgery (n =
      4); or no doxycycline (n = 6). RESULTS: Five days of doxycycline treatment, in a
      dose of either 100 mg bid or 100 mg qam, inhibited gelatinase activity in the
      cartilage extracts (p = 0.003, 0.008, respectively). The bid dose also inhibited
      collagenase activity (p = 0.002), but inhibition of collagenase with 100 mg qam
      did not quite reach statistical significance (p = 0.055), in comparison with the
      values for the untreated OA controls. The single 200 mg dose, given 3 days before
      procurement of the cartilage, was ineffective in inhibiting metalloproteinase
      activity. CONCLUSION: Oral administration of doxycycline significantly inhibited
      collagenase and gelatinase activity in human OA cartilage. The effective dose is
      likely to be well tolerated during chronic administration, e.g., in a clinical
      trial to assess the potential of the drug to modify cartilage breakdown in OA.

PMID- 9517777
TI  - Influence of antirheumatic drugs on nitric oxide and interleukin 8 production in
      human articular chondrocytes.
AB  - OBJECTIVE: To determine whether antirheumatic drugs can inhibit chondrocyte
      nitric oxide and interleukin 8 (IL-8) production. METHODS: IL-1beta stimulated
      human chondrocytes were incubated with indomethacin, methotrexate, sulfasalazine,
      dexamethasone, and methylprednisolone. Nitric oxide was detected as nitrite; IL-8
      was detected by a radioimmunoassay method. RESULTS: Nitric oxide production was
      partly (< or = 50%) inhibited and IL-8 almost completely suppressed (> 80%) by
      dexamethasone and methylprednisolone. Sulfasalazine in pharmacological
      concentration and indomethacin slightly increased IL-8. No effect of methotrexate
      on nitric oxide or IL-8 production was found. CONCLUSION: Dexamethasone and
      methylprednisolone are inhibitors of human chondrocyte nitric oxide production,
      although to a lesser extent than for IL-8 production. Indomethacin,
      sulfasalazine, and methotrexate had no major influence on these mediators.

PMID- 9517778
TI  - Upregulation of CD44 in the inflamed mouse air pouch injected with synthetic
      lipid A.
AB  - OBJECTIVE: To investigate aspects of the inflammatory process of the mouse
      subcutaneous air pouch -- a facsimile synovial cavity -- induced by injection of
      lipid A, and to determine the expression and upregulation of CD44 in the lining
      cell layer of the inflamed air pouch. METHODS: Histological changes of inner
      walls in the mouse air pouch were evaluated 1, 3, and 7 days after injection of
      lipid A. RESULTS: Polymorphonuclear cell infiltration in the lining layer reached
      the maximum one day after injection of 10 microg of lipid A (10/10 mice in Grade
      3; p < 0.01), while mononuclear cell infiltration and lining cell hyperplasia
      reached the maximum 3 days after injection (5/10 mice in Grade 2; 5/10 in Grade
      3; p < 0.05; 39+/-11 layers, p < 0.05, respectively). The number of cell depth of
      CD44 positive lining layers and interleukin 1alpha (IL-1alpha) positive lining
      layers reached the maximum 3 days after injection (39+/-7 layers, p < 0.01; 35+/
      12 layers, p < 0.05, respectively). CONCLUSION: These findings suggest that CD44
      may have some connection with the proinflammatory cytokine IL-1alpha and induce
      inflammatory responses in the air pouch injected with lipid A.

PMID- 9517779
TI  - What use are fibromyalgia control points?
AB  - OBJECTIVE: To investigate the relationship between control points and symptom and
      distress severity in fibromyalgia (FM). METHODS: Eighty-four new patients with FM
      seen at an outpatient rheumatology center from December 1994 through August 1996
      underwent tender point and dolorimetry examinations at 18 active and 4 control
      sites. All completed the assessment scales for fatigue, sleep disturbance,
      anxiety, depression, global severity, pain, and functional disability, and a
      composite measure of distress constructed from scores of sleep disturbance,
      fatigue, anxiety, depression, and global severity -- the Rheumatology Distress
      Index (RDI). RESULTS: Control point positivity was common in FM (63.1%) and was
      associated with somewhat more severe FM symptoms and general distress, yielding
      an increase in the RDI of 9.2 units or 0.55 standard deviation units. There was
      no evidence of particularly worse disease in patients with high counts of control
      tender points, and increasing numbers of tender points beyond the first positive
      control point were generally not associated with, or were only weakly associated
      with, increasing symptom severity. Many patients with positive control points had
      only mild levels of symptom severity. Finally, we found no clusters of patients
      with very severe symptoms associated with control points, or with dolorimetry
      scores, or with ratios of dolorimetry scores from different body regions of
      varying pain thresholds. CONCLUSION: Positive control points are a common feature
      (63%) in FM, and appear to be a marker for a generally low pain threshold rather
      than a disproportionate increase in severe symptoms or distress. Control point
      positivity should not be used to disqualify a diagnosis of FM. Control point
      measurements do not add much to FM diagnosis or assessment and, perhaps, should
      be abandoned. At the least, they should be designated "high threshold" points
      rather than control points. Dolorimetry is considerably less useful in FM
      assessment than the manual tender point examination.

PMID- 9517780
TI  - Normal melatonin levels in patients with fibromyalgia syndrome.
AB  - OBJECTIVE: To assess urine levels of melatonin measured by 6-sulphatoxymelatonin
      (aMT6s) in patients with fibromyalgia (FM). METHODS: Nocturnal aMT6s urine levels
      were measured by ELISA, in a sample of urine collected from 10 PM to 7 AM from 39
      female patients with FM and 39 age matched healthy female controls. All subjects
      were interviewed and assessed for nonarticular tenderness, FM symptoms, quality
      of life, and physical functioning. RESULTS: Nocturnal aMT6s levels of patients
      with FM were not statistically different from those of controls: 16.7+/-9.2 vs
      16.0+/-11.3 microg, respectively. No association was observed between aMT6s
      levels of patients with FM and disease duration, reproductive status, sleep and
      mood disturbances. CONCLUSION: Nocturnal urine aMT6s levels were similar in
      patients with FM and controls. Studies are needed to elucidate the possible role
      of melatonin in FM and should include larger samples of newly diagnosed untreated
      patients with FM.

PMID- 9517781
TI  - Use of dynamic magnetic resonance imaging to detect sacroiliitis in HLA-B27
      positive and negative children with juvenile arthritides.
AB  - OBJECTIVE: Involvement of the sacroiliac (SI) joints is a hallmark of the
      spondyloarthropathies (SpA), especially, in early and later stages of ankylosing
      spondylitis in adults. The significance of sacroiliitis in juvenile SpA is less
      clear and the diagnosis of juvenile SpA is difficult due to the mostly
      nonspecific or absent history of back pain in children and the time delay
      associated with the diagnosis of sacroiliitis by conventional radiographs. Our
      aim was to evaluate dynamic magnetic resonance imaging (MRI) of the SI joints in
      children and to assess the frequency and the determinants of SI joint involvement
      in juvenile SpA and other juvenile arthritides. METHODS: Clinical examinations
      and dynamic MRI were performed in 130 children < 16 years of age with joint
      complaints, 100 with probable SpA, and 30 controls. The degree of back pain was
      assessed by a visual analog scale (VAS) (0 = no pain, 10 = very severe pain). The
      following groups were defined before MRI investigation according to modified
      European Spondylarthropathy Study Group (ESSG) criteria for SpA: Group 1:
      undifferentiated SpA (uSpA, n = 41, 88% B27+); Group 2: differentiated SpA (n =
      29, 97% B27+), comprising reactive arthritis (n = 16), ankylosing spondylitis (n
      = 9), psoriatic arthritis (n = 3), and arthritis in inflammatory bowel disease (n
      = 1); Group 3: patients with no signs of SpA other than oligoarthritis, here
      named juvenile chronic arthritis (JCA) II (n = 30, 93% B27+); Group 4: HLA-B27+
      controls without arthritis (n = 12); and Group 5: HLA-B27-controls with various
      other non-SpA diagnoses (n = 18). MRI was evaluated according to published
      criteria allowing for differentiation between acute and chronic changes in SI
      joints. RESULTS: Acute sacroiliitis without chronic changes could only be
      detected by dynamic MRI: in 17 patients (11 in Group 1, 3 in Group 2, 3 in Group
      3) together in 14/70 (20%) patients with SpA. All these 17 patients had normal
      pelvic radiographs. Using MRI acute and/or chronic sacroiliitis were found in 35
      patients: 17/41 in Group 1 (41%), 15/29 in Group 2 (52%), and 3/30 (10%) patients
      in Group 3, but in no patients in Groups 4 and 5. Chronic SI joint changes >
      grade 1 were detected by MRI in 18/70 patients with SpA (25.7%). In comparison,
      radiographic changes > grade 1 were less often detected in 14/70 patients with
      SpA (20%) or 23/210 SI joints examined (11 %), compared to 29/210 SI joints found
      in the MRI examinations (14%) (p = 0.05). Among the 70 patients with SpA, those
      with MRI diagnosis of acute sacroiliitis had a significantly longer disease
      duration (62+/-34 vs 28+/-16 months; p = 0.01) and higher C-reactive protein
      (12+/-12 vs 9+/-14; p = 0.01), and also reported more back pain on VAS (4.3+/-3.6
      vs 1.2+/-2.2; p = 0.001) than those without sacroiliitis. CONCLUSION: Dynamic MRI
      and MRI are useful to detect acute and chronic sacroiliitis in children. The main
      advantages in comparison with conventional radiographs are the ability to detect
      acute changes in the SI joints, the higher sensitivity to detect chronic changes,
      and clearly, the lack of radiation exposure; while the disadvantages are the high
      costs and the duration of the procedure. Sacroiliitis is fairly common in
      juvenile SpA and seems to be associated with disease intensity and duration.

PMID- 9517782
TI  - Adjustment in patients with rheumatoid arthritis and their children.
AB  - OBJECTIVE: To assess everyday life stress and emotional adjustment in patients
      with rheumatoid arthritis (RA) and their children. METHODS: We conducted a 6
      month study of 14 patients with RA with children aged 4-16 years (25 children)
      and 24 control families (53 children). Life event stress and functional capacity
      were assessed at the beginning and end of the study, and minor stressors
      (hassles), positive events (uplifts), and salivary cortisol were recorded weekly.
      Emotional adjustment was measured monthly in adults by self-report, and bimonthly
      in children using the Child Behavior Checklist (completed by parents). Social
      support and psychological coping responses were also measured. RESULTS: Patients
      with RA experienced fewer positive events than did controls, and they tended to
      have smaller support networks. Daily hassle levels correlated with severity of
      disability, and differences in psychological coping were also observed. Children
      from RA families reported nearly 50% more hassles per week than did controls, and
      their social networks were significantly smaller. They were rated as having
      greater problems of social adjustment than controls. Cortisol concentration was
      greater among children who experienced more life event stress over the study
      period, but did not differ between groups. CONCLUSION: The patients with RA in
      this study showed good adaptation, but experienced less pleasure in their daily
      lives. The children of patients with RA may have heightened vulnerability to
      stress related problems, with fewer social resources and difficulties in
      behavioral adjustment.

PMID- 9517783
TI  - Methotrexate therapy in refractory pediatric onset systemic lupus erythematosus.
AB  - OBJECTIVE: To evaluate the efficacy, safety, and corticosteroid sparing potential
      of methotrexate (MTX) in patients with pediatric onset systemic lupus
      erythematosus (SLE). METHODS: The medical records of 11 patients with SLE with
      onset before age 16 years were reviewed. Details of clinical features, previous
      therapy, indications for MTX, efficacy, toxicity, and corticosteroid reduction
      during MTX therapy were recorded. RESULTS: At the start of MTX treatment, 7
      patients had nephritis, 3 malar rash, 3 arthritis, 2 skin vasculitis, and 2
      thrombocytopenia. All patients were given MTX (12.5-17.0 mg/m2/week) as the sole
      drug therapy along with prednisone. Although many patients showed initial
      improvement and/or were able to reduce the prednisone dose, after 7 to 23 months
      8 patients had a flare of SLE requiring increased doses of prednisone, one
      patient had unchanged SLE activity, and 2 patients were permanently discontinued
      from MTX because of toxicity. Side effects were observed in 8 (73%) patients, but
      only 2 (18%) discontinued MTX due to toxicity. CONCLUSION: MTX given as the sole
      drug therapy along with prednisone did not show a major corticosteroid sparing
      potential in our patients with pediatric onset SLE.

PMID- 9517784
TI  - Single photon emission computed tomography scanning in childhood systemic lupus
      erythematosus.
AB  - OBJECTIVE: To determine the role of central nervous system (CNS) perfusion
      scanning in detecting CNS disease in childhood onset systemic lupus erythematosus
      (SLE) and serial single photon emission computed tomography (SPECT) scans in
      monitoring CNS disease activity in childhood. METHODS: The charts of 108 patients
      with a confirmed or suspected diagnosis of SLE during the period February 1987 to
      June 1992 were reviewed. Twenty patients with a diagnosis of CNS SLE and 10
      patients without CNS involvement had at least one SPECT scan. Patients were
      divided into (a) focal CNS SLE, when there were clinical manifestations that
      could be attributed to localized lesions of the CNS (6 patients); and (b) diffuse
      CNS SLE, when there was a global defect in CNS function including organic brain
      syndrome, psychosis, and depression (14 patients). If a patient had both diffuse
      and focal CNS disease that patient was designated as having diffuse disease.
      Forty-three patients with a diagnosis other than SLE comprised our non-SLE
      control group. RESULTS: SPECT scans were performed in 20 patients with acute CNS
      involvement. In patients with acute diffuse CNS disease, diffuse patchy areas of
      hypoperfusion were seen in 86% of patients at presentation of the CNS event. In
      the focal CNS disease subgroup, 33% of patients had an abnormal scan at CNS
      presentation. In these patients focal rather than diffuse abnormalities were
      seen. Eight patients with diffuse CNS SLE had at least one followup study at
      intervals ranging from 1 month to 3 years after initial scan. In 50% of these
      patients with diffuse CNS involvement, improvement in their abnormal scan
      correlated with clinical improvement, while in the other 50% clinical improvement
      was not associated with SPECT scan improvement. The most common abnormal SPECT
      scan pattern in patients with CNS SLE was one of widespread multiple small areas
      of decreased uptake at multiple sites, suggestive of generalized patchy
      hypoperfusion. Although SPECT scans were sensitive to the presence of CNS
      disease, the diffuse hypoperfusion was not specific for clinically detectable CNS
      involvement. In patients with SLE, a diffusely abnormal scan had a specificity of
      69% and a likelihood ratio of 2.2 to correctly detect overt diffuse CNS disease.
      CONCLUSION: Although we found that SPECT scanning was a highly sensitive method,
      it was not a specific method in correctly diagnosing diffuse CNS SLE in children.
      However, the presence of an abnormal SPECT scan in SLE patients with no history
      of overt CNS SLE may suggest that subclinical CNS disease may be more common in
      children than previously suggested.

PMID- 9517785
TI  - Regional cerebral blood flow in juvenile systemic lupus erythematosus: a
      prospective SPECT study. Single photon emission computed tomography.
AB  - OBJECTIVE: Using single photon emission computed tomography (SPECT) we evaluated
      the presence and evolution of changes in brain perfusion in juvenile systemic
      lupus erythematosus (JSLE). METHODS: SPECT was performed in 14 patients with
      active JSLE divided in 2 groups: the first included 7 patients without central
      nervous system (CNS) involvement and the second 7 patients with minor
      neuropsychiatric symptoms (headache, reactive depression, cognitive impairment,
      mood swing). SPECT findings were compared to seroimmunological and magnetic
      resonance imaging (MRI) data. After 6 month followup, a second SPECT scan was
      performed in 12 of 14 patients. RESULTS: At baseline, SPECT showed perfusion
      defects in 2 patients without neuropsychiatric symptoms and in 5 patients with
      CNS involvement. In one of the 7 patients with altered SPECT, MRI showed focal
      hyperintensities. MRI alterations were observed in another patient who had a
      normal SPECT scan. Cortical atrophy was present in 5 of 14 patients. Correlation
      between neuropsychiatric manifestations and SPECT findings was not clearly
      evident because the major part of JSLE patients with CNS involvement and with
      SPECT alterations had multiple symptoms, but showed focal hypoperfusion on SPECT
      imaging. No significant association was found between seroimmunological data and
      SPECT findings. At followup, improvement of perfusion alterations was observed in
      6 of 7 patients with altered SPECT and, in 3 of them, findings might be
      attributed to changes in steroid treatment. CONCLUSION: Perfusion abnormalities
      in SLE may represent reversible lesions or subclinical CNS involvement. Moreover,
      SPECT imaging appears to be useful in detecting and monitoring CNS involvement in
      SLE.

PMID- 9517786
TI  - Sudden sensorineural hearing loss in patients with systemic lupus erythematosus
      or lupus-like syndromes and antiphospholipid antibodies.
AB  - Although the pathogenesis of sudden sensorineural hearing loss (SNHL) in patients
      with systemic lupus erythematosus (SLE) is not clear, several reports suggest an
      association with the antiphospholipid antibody (aPL). We describe 6 patients with
      SLE or a lupus-like syndrome, who had sudden SNHL and had elevated levels of
      anticardiolipin antibodies (aCL) or the lupus anticoagulant. In a literature
      search, of 5 additional reported cases, 2 were not tested for aPL; the remaining
      3 had elevated aCL levels. Thus, acute SNHL in patients with SLE who have aPL may
      be a manifestation of the antiphospholipid syndrome. We recommend anticoagulation
      treatment of these patients.

PMID- 9517787
TI  - Uveitis and central nervous system vasculitis.
AB  - Vasculitis confined to the central nervous system (CNS) is a rare disease usually
      characterized by headache and focal neurologic symptoms. Patients with primary
      vasculitis of the CNS may have symptoms and laboratory findings of systemic
      disease such as fatigue and elevated erythrocyte sedimentation rate, but by
      definition, focal inflammation should not be present outside the CNS. We describe
      3 patients with uveitis in association with this diagnosis. The recognition of
      this association adds to the complex differential diagnosis of uveitis in
      association with CNS disease, and indicates that "isolated" angiitis of the CNS
      may display clinical features outside the brain and spinal cord.

PMID- 9517789
TI  - Back to the future: the pyramids of rheumatoid arthritis.

PMID- 9517788
TI  - Olecranon bursitis caused by infection with Candida lusitaniae.
AB  - We describe a 59-year-old woman with diabetes and chronic asthma treated with
      prednisone and methotrexate who developed chronic olecranon bursitis caused by
      Candida lusitaniae. Infection, especially with unusual microbial pathogens,
      should be considered in cases of chronic bursitis in patients taking
      immunosuppressive medicine, even if the classic signs of septic bursitis are
      absent. Infection with C. lusitaniae, a component of the normal mycoflora, may be
      a marker of serious immunosuppression, as this patient ultimately died of a
      Pneumocystis carinii infection.

PMID- 9517790
TI  - Acute phase and function in rheumatoid arthritis.

PMID- 9517791
TI  - Routine measurement of IgM, IgG, IgA rheumatoid factors.

PMID- 9517792
TI  - Aseptic avascular osteonecrosis mimicking arthritis in HIV infection.

PMID- 9517793
TI  - Association between osteoarthritis of the hand and hip.

PMID- 9517794
TI  - Treatment of eosinophilic fasciitis with methotrexate.

PMID- 9517795
TI  - Computerized cardiotocography following vibroacoustic stimulation of premature
      fetuses.
AB  - OBJECTIVE: The purpose of this study was to examine the effect of vibroacoustic
      stimulation (VAS) on the fetal heart rates (FHRs) in a group of premature
      fetuses. STUDY DESIGN: The FHRs were analyzed using the Oxford Sonicaid Computer
      System 8000, 30 min preceding and then 3 times following VAS. RESULTS: The
      changes of the mean FHR after VAS in the premature group and the control group of
      term fetuses occurred in the first 10 min after VAS. The greatest increase in the
      number of accelerations occurred in both groups during the 11-20 min following
      VAS. The long-term variability increased significantly in all 3 study periods in
      premature fetuses and only in the periods of 0-10 and 11-20 min in the control
      group. The increase in short-term variability was similar in both groups and it
      was greatest in the period of 11-20 min. CONCLUSION: Most of the heart rate
      changes of premature fetuses occur between 11 and 20 min following VAS.

PMID- 9517796
TI  - Antepartum risks of shoulder dystocia and brachial plexus injury for infants
      weighing 4,200 g or more.
AB  - A cohort of 236 vaginally delivered neonates weighing > or = 4,200 g was
      evaluated. Shoulder dystocia was encountered in 27 deliveries (11.4%) and
      brachial plexus injury was diagnosed in 3 infants (1.3%). The 'traditional'
      antepartum risk factors could not be associated with shoulder dystocia. In this
      cohort, primiparity was significantly more frequent among the dystocia cases (OR
      = 8.58, 99% CI = 1.35-54.35, p = 0.021). Shoulder dystocia could not be
      attributed to a particular difference between the current and the previous
      heaviest birth weight. A policy of cesarean section for all infants weighing > or
      = 4,200 g would result in at least 5- to 6-fold increase in cesarean rate in this
      group of patients. Our data reconfirm that shoulder dystocia and brachial plexus
      injury are unpredictable, even in macrosomic infants. It is a matter of policy
      whether to accept the expected 1:9 and 1:79 respective risks associated with
      vaginal births.

PMID- 9517797
TI  - Antiphospholipid antibodies in eclamptic women.
AB  - Our purpose was to determine the prevalence of antiphospholipid antibodies (APA)
      in eclamptic women as well as the rates of intrauterine growth retardation (IUGR)
      and fetal death in APA-positive and -negative eclamptic women. Thirty-six
      eclamptic and 30 healthy pregnant women were enrolled in this study. APA in those
      groups were determined. The prevalences of IUGR and fetal death were determined
      in APA-positive and -negative eclamptic women. In the eclamptic group, APA were
      positive in 9 out of 36 patients (25%), where as only 2 out of 30 controls (6.7%)
      were positive (p < 0.05). Fetal death was encountered in 4 out of 9 (44.4%) APA
      positive eclamptic women; this was a significantly larger proportion than that
      for APA-negative eclamptic women (1/27; p < 0.01). The rates of IUGR in APA
      positive and -negative eclamptic women were not significantly different (p >
      0.05). Similar conclusions about our results could also be made, when weakly
      positive anticardiolipin antibodies were regarded as negative in our study group
      and controls. Our study suggests that positive levels of APA in eclamptic women
      increase the risk for intrauterine fetal death.

PMID- 9517798
TI  - Postpartum uterine-artery velocity waveforms in women with sickle cell disease.
AB  - OBJECTIVE: To investigate the changes in uterine Doppler velocimetry during the
      postpartum period in women with homozygous sickle cell (SS) disease and to
      correlate these findings with values in the third trimester and with neonatal
      outcomes. METHODS: We studied the postpartum changes in uterine Doppler
      velocimetry in 16 women with SS disease in relation to third-trimester
      systolic/diastolic (S/D) ratios and neonatal outcome. All patients had repeated
      measures of uterine S/D ratios biweekly in the third trimester from 28 weeks of
      pregnancy until delivery, and at 24 h, and 3 and 6 weeks postpartum. RESULTS:
      Overall the mean S/D ratio in the first 24 h for these 16 women was 2.72 +/- 0.72
      and increased progressively to a mean S/D ratio of 6.88 +/- 0.96 at 6 weeks
      postpartum, with the reappearance of a diastolic notch by the 3rd postpartum
      week. Twelve women who had normal (< or = 2.6) uterine S/D ratios during
      pregnancy delivered appropriate-for-gestational-age (AGA) infants. The remaining
      4 women had abnormal uterine S/D ratios, and in 3 of these pregnancies, small-for
      gestational-age (SGA) infants were delivered. The mean S/D ratios for the
      subgroups with abnormal value at each of the three postpartum periods were
      significantly higher than for the 12 SS patients with normal third-trimester
      values. Postpartum S/D ratios for the 3 women with SGA births were also
      significantly higher at 24 h and 6 weeks postpartum when compared to SS patients
      with AGA infants. CONCLUSION: We concluded that postpartum S/D ratios are higher
      in women with SS disease that have abnormal values in the third trimester and
      that they are associated with SGA births. In SS patients the nonpregnant pattern
      of uterine artery velocity waveforms which reappears postpartum may reflect an
      increase in the uteroplacental circulatory impedence due to reversal of the
      alterations in the spiral arteries induced by trophoblastic invasion during
      pregnancy or subinvolution of the placental bed. Additional studies are needed to
      further elucidate these important hemodynamic changes in women with
      hemoglobinopathies and to identify patterns predictive of neonatal outcomes in
      these high-risk patients.

PMID- 9517799
TI  - Changes in plasma elastase during pregnancy and sub partu.
AB  - Elastase is produced and released by polymorphonuclear leukocytes (PNMs) during
      inflammatory processes. Thus, elastase is assumed to be a sensitive marker of
      infections similar to the well-established C-reactive protein (CRP). It is
      deactivated predominantly in tissues by alpha1-proteinase inhibitor which forms
      stable complexes with the elastase molecule (EAPI) that can be detected for
      several hours. Premature rupture of membranes is often correlated with an early
      increase in elastase, occurring earlier than the increase in leukocyte count or
      CRP. Elastase might be a sensitive marker of beginning amnion infection syndrome
      after premature rupture of membranes. For the present study, plasma EAPI levels
      of 335 healthy pregnant women as well as 47 healthy nonpregnant pre- and
      postmenopausal women were analyzed. No significant differences were found in the
      latter group or in pregnant women until the beginning of labor. Women at the
      beginning of labor but without rupture of membranes showed a significant increase
      in plasma EAPI from 97.7 to 338.3 ng/ml (p < 0.001). With opening of the os uteri
      to more than 2 cm, elastase concentrations decreased to values comparable to
      those before the beginning of labor (p < 0.001). The use of elastase as a marker
      for a rupture of membranes or beginning amnion infection syndrome as suggested by
      a number of studies might need some restriction. As a consequence, serial
      monitoring of plasma elastase to detect a persisting increase might give more
      reliable results. The increase in plasma elastase during beginning of labor may
      be explained by the role of PMNs in the physiology of delivery. However, serial
      monitoring to detect a persisting increase in plasma EAPI may be more helpful.

PMID- 9517800
TI  - Side effects of tamoxifen in oophorectomized rats.
AB  - OBJECTIVE: Our objective was to evaluate the direct effect of tamoxifen citrate
      (TAM) on the endometrium, liver, breast tissue and the lipid profile in
      oophorectomized (OX) rats. STUDY DESIGN: An experimental animal study. MATERIAL
      AND METHODS: Forty-one mature rats (33 OX) were randomly divided into four groups
      and received either TAM (0.4 or 0.8 mg/kg p.o.) therapy or placebo over 60 days
      as follows: (1) sham; (2) OX + TAM (0.4 mg/kg); (3) OX + TAM (0.8 mg/kg); (4) OX.
      All histological changes in the endometrium, liver and breast tissue were
      evaluated under the light microscope by comparing the TAM-treated groups with the
      OX and sham-operated groups. Blood total cholesterol and low-density lipoprotein
      cholesterol levels were also analyzed. RESULTS: TAM-treated rats showed a
      significant reduction in body weight, blood cholesterol and low-density
      lipoprotein cholesterol levels, but the wet uterine weight was not affected.
      Estrogenic effects of TAM were not detected with either dosage on the
      endometrium. TAM-treated groups showed atrophic breast tissue. No
      histopathological changes were detected in the liver with TAM treatment.
      CONCLUSION: The data suggests that TAM may not act as an estrogen receptor
      agonist with the given dosage on the endometrium in OX rats. Two different doses
      of TAM do not cause histological changes in liver over 60 days of treatment.

PMID- 9517801
TI  - Elevation in plasma alkaline phosphatase level during rhG-CSF administration.
      Granulocytopenic patients with gynecologic cancers treated with cancer
      chemotherapy.
AB  - Neutropenic patients suffering from gynecologic cancers treated with cancer
      chemotherapy were evaluated to investigate changes in levels of plasma alkaline
      phosphatase (ALP) during recombinant human granulocyte colony stimulating factor
      (rhG-CSF) administration, and to discern its causes. Plasma ALP, ALP isozymes,
      neutrophil alkaline phosphatase (NAP) activity, and morphological maturation of
      neutrophils were measured prior to, during, and after rhG-CSF administration.
      Plasma ALP values were significantly elevated (p < 0.05) during administration of
      rhG-CSF. ALP-3, the dominant alkaline phosphatase fraction of NAP, was the
      dominant isozyme that showed an increase in the plasma. Moreover, the elevation
      of plasma ALP-3 significantly correlated with the elevation of NAP activity (r =
      0.939, p < 0.0001), and neutrophils in which NAP activity was induced were not
      limited to morphologically mature neutrophils. These results showed that rhG-CSF
      acts to stimulate neutrophils at all stages of maturation and causes an elevation
      of plasma ALP(ALP-3) concentrations in plasma.

PMID- 9517802
TI  - Symptoms of defective emptying and raised residual urine may arise from
      ligamentous laxity in the posterior vaginal fornix.
AB  - OBJECTIVES: To prospectively test the hypothesis that laxity in the posterior
      ligaments of the vagina may cause raised residual urine and abnormal emptying
      symptoms. METHODS: Eighteen patients, 16 multiparous, and 2 nulliparous, were
      referred with symptoms of abnormal bladder emptying. All were assessed with
      standard cystometry and standing resting and straining lateral X-ray films, with
      the bladder containing a Foley balloon catheter containing 10 ml of radio-opaque
      dye. Three patients were also assessed with videocystourethrograms, and these
      were compared to 4 normal controls. A posterior fornix repair was performed. A
      full thickness horizontal vaginal incision was made using a scalpel. The incision
      was stretched antero-posteriorly, and the utero-sacral and cardinal ligaments
      tightened by suturing them side to side. RESULTS: Specific symptoms of defective
      opening were reduced from a total of 43 pre-operatively to 9 post-operatively.
      Mean residual urine was reduced from 98.7 to 31.7 ml (p < OR = 0.028). Peak flow
      increased from 29.7 to 34.2 ml/s, p < OR = 0.08. Mean flow pre-operative was 8.18
      ml/s, and post-operative flow 8.6 ml/s (p < OR = 0.88). Mean emptying time
      decreased from 65.3 to 60.4 s. CONCLUSIONS: Reference to radiographs in normal
      patients demonstrates that bladder funnelling is associated with a powerful
      downward force transmitted to the coccyx via the utero-sacral ligaments.
      Correction of laxity in the utero-sacral ligaments, the effective insertion
      points of the downward force, improved bladder emptying. This appears to sustain
      the hypothesis that abnormal bladder emptying in the female may be at least
      partly caused by ineffectiveness of the opening muscles, because of laxity in
      their insertion points.

PMID- 9517803
TI  - Detection of herpes simplex virus (HSV) in aborted material using the polymerase
      chain reaction technique.
AB  - OBJECTIVE: To investigate the contribution of HSV to the aetiopathogenesis of
      spontaneous abortion. DESIGN: A hospital-based, case-control study. SETTING:
      Department of Obstetrics and Gynecology, University Hospital and Laboratory of
      Clinical Virology, Medical School, University of Crete, Heraklion, Crete, Greece.
      POPULATION AND METHODS: Abortion material from 102 cases of women with
      spontaneous abortion was analysed for the presence of HSV DNA applying the PCR
      technique. Serological assays were used for the detection of specific IgM and IgG
      antibodies in the maternal sera of 90 pregnant women with successful outcome of
      their pregnancy while 70 non-pregnant women at reproductive age were also
      examined as control. RESULTS: The HSV genome was detected by PCR amplification in
      3 cases of spontaneous abortion, 2 of them exhibited serological markers of virus
      reactivation while the 3rd showed a past infection. There were no obvious
      clinical manifestations indicating a current herpes infection. Both groups of
      pregnant women, either with spontaneous abortion or with a successful outcome of
      pregnancy, displayed serological markers of HSV reactivation at higher rates
      compared with non-pregnant women (chi2, p < 0.05). CONCLUSIONS: Using the PCR
      technique we were able to detect the HSV genome in gestational tissues of
      spontaneous abortions, even in cases without any clinical symptoms or
      seropositivity for a primary infection. Serological assays were not very useful
      for the elucidation of the role of HSV in inducing spontaneous abortions,
      although they indicate that the state of pregnancy predisposes to HSV
      reactivation. However, the detection of HSV in 3 out of a total number of 102
      cases does not support HSV infection as a major abortion-related factor.

PMID- 9517804
TI  - Cervical dilatation: induction by antigestagens via adhesion molecules. An in
      vitro examination in endothelial cell cultures.
AB  - Cervical ripening at term resembles an inflammatory reaction with invasion of
      activated granulocytes into the cervical stroma. Our objective was to investigate
      the influence of the antigestagen onapristone alone and in combination with other
      substances associated with cervical ripening on the expression of the
      inflammation-associated adhesion molecules ELAM-1, ICAM-1 and VCAM-1. Human
      endothelial cell cultures were stimulated with onapristone (200 ng/ml), TNF-alpha
      (100 U/ml), IL-8 (20 ng/ml) and PGE2 (3 ng/ml) separately and in combination (n =
      6). The expression of adhesion molecules was determined qualitatively and
      quantitatively by immunofluorescence staining and flow cytometry with statistical
      evaluation by Kolmogorov-Smirnov analysis. Onapristone upregulated slightly the
      expression of ELAM-1 (19%). The costimulation of onapristone and TNF-alpha
      provoked an additive expression of VCAM-1 (64%) beyond the effect of TNF-alpha
      alone, while the costimulation of onapristone and PGE2 as well as the combination
      with IL-8 did not result in an additional stimulatory effect. All results were
      statistically significant (p < 0.001). This result supports our hypothesis that
      onapristone may lead to an increased adhesion of granulocytes to the capillary
      endothelium thereby initiating cervical ripening.

PMID- 9517805
TI  - Endometrium-to-myometrium relative echogenicity coefficient. A new sonographic
      approach for the quantitative assessment of endometrial echogenicity.
AB  - A computer program was developed to assess the endometrial echogenicity relative
      to the myometrial one, based on the gray-level processing of the midsagittal
      uterine image. The endometrial region of interest was specified within the upper
      part of the uterine cavity. The adjacent area of the myometrium was used to
      determine the reference brightness. The endometrial region of interest was
      analyzed along the anteroposterior uterine axis, as a set of thin strips directed
      parallelly to the midcavitary line. The endometrial/myometrial relative
      echogenicity coefficient (E/M REC) was computed for each strip and displayed
      graphically as a function of the distance from the midcavitary line. The area
      under the E/M REC curve within the limits of the total endometrial width was
      defined as total area (TA) and was used as a measure of the endometrial
      echogenicity. This parameter was assessed in 9 patients during their normal
      ovulatory cycles and in 29 IVF-treated patients with mechanical infertility. TA
      has a significant linear increase during the days of the ovulatory cycles. TA was
      found in high correlation with log(estradiol). TA can be used reliably for
      sonographic endometrial dating in ovulatory cycles.

PMID- 9517806
TI  - Estrogen and progesterone receptors of adenomyosis in postmenopausal breast
      cancer patients treated with tamoxifen.
AB  - Adenomyosis is an ectopic endometrial tissue located in the myometrium. It has
      been reported to develop at a higher rate among postmenopausal breast cancer
      patients on tamoxifen (TAM) treatment than in untreated patients. It has also
      been reported to be stimulated by estrogen. Assessing receptor levels in
      adenomyotic tissue may indicate the adenomyotic cell's potential to interact with
      TAM. In the present study the estrogen receptor (ER) and progesterone receptor
      (PR) were analyzed by an immunohistochemical technique in adenomyotic and the
      corresponding endometrial tissues of 14 postmenopausal breast cancer patients
      treated with TAM and in 15 healthy postmenopausal patients who served as
      controls. All TAM-treated patients had normal postmenopausal serum estradiol
      levels. Overall the ER and PR contents in adenomyotic tissue (42.9 and 71.4%) and
      in the endometriotic tissue (64.3 and 78.6%) obtained from the study patients
      were similar to those obtained from the control group (adenomyosis, ER and PR =
      46.7 and 86.7%; endometrium, ER and PR = 40 and 73.3%; p = NS). In the study
      group, the ER content was lower in the adenomyotic (42.9%) than in the
      endometriotic tissue (64.3%). No correlation was found between the duration of
      TAM therapy, the TAM dosage level or the ER or PR content in the adenomyotic or
      endometrial tissues. The finding of a relatively low ER content in the
      adenomyotic tissue than in the endometriotic tissue in postmenopausal TAM-treated
      patients without endogenous estrogens, similar to that observed in healthy
      premenopausal women, may be attributed to the estrogen-like effect of TAM.

PMID- 9517807
TI  - Management of malignant ovarian tumors in young women. 21 nulliparous cases.
AB  - To evaluate the management of malignant ovarian tumors in young women who wish to
      maintain fertility, we retrospectively reviewed ovarian malignancies in 21 young
      women who were both nulliparous and under 40 years of age. With stage 1a disease,
      all 9 patients were treated with conservative surgical therapies, and all of them
      are still alive, irrespective of histological type. With stage 1c disease, 5
      (83%) of 6 patients were treated with conservative surgical therapies. Among
      them, 2 patients with epithelial tumors, who were treated with conservative
      surgical therapies and potent cis-diamminedichloroplatinum (CDDP)-based combined
      chemotherapies, are still alive. Furthermore, one of them had a successful
      pregnancy. On the other hand, 3 out of 4 patients with nonepithelial tumors were
      treated with conservative surgical therapies. However, 2 (67%) out of 3 died;
      both of them were treated with non-CDDP-based chemotherapy. In 6 patients with
      disease beyond stage 2, 4 (67%) were treated with radical surgical therapies, but
      2 (33%) were treated with conservative surgery and CDDP-based combined
      chemotherapy, one of which was followed by a successful pregnancy in spite of
      nonepithelial tumor. As above, we could obtain some successful pregnancies in
      cases beyond stage 1c after conservative surgery by adding definite CDDP-based
      combined chemotherapy. However, we must carefully select the patients with
      nonepithelial tumors for conservative therapy by adding definite CDDP-based
      combined chemotherapy and inform them of the risks of therapy.

PMID- 9517808
TI  - Complications of radical hysterectomy: clinical experience of 115 early stage
      cervical cancers.
AB  - We evaluated the clinical experience of 115 women with early stage cervical
      cancer who had been operated in our Gynecologic Oncology Clinic. Of these, 85
      were in stage I, and 30 in stage II. Intraoperative complications occurred in 16
      patients including 3 cases concerning bladder, 1 ureter, 1 aorta, 5 v.cava
      inferior, 1 internal iliac a., 3 internal iliac v., 1 obturator nerve and 1
      rectovaginal septum hematoma formation. Postoperative complications were observed
      in 38 patients. These were 14 bladder dysfunctions, 10 lymphocyst formations, 6
      urinary infections, 12 wound infections, 3 pelvic infections, 2 eviscerations and
      1 incisional hernia. However, no death occurred due to intraoperative or
      postoperative complications. Pelvic lymph node metastases were observed in 32
      patients of whom 17 had only unilateral involvement, most often in the obturator
      region. Para-aortic lymph node metastases were diagnosed in 4 patients, all of
      whom were in stage II.

PMID- 9517810
TI  - Ovulation induction and breast cancer.

PMID- 9517809
TI  - Paraneoplastic cerebellar degeneration with anti-Purkinje cell antibody
      associated with primary tubal cancer.
AB  - In patients with paraneoplastic cerebellar degeneration (PCD) due to gynecologic
      malignancies, a high titer of anti-Purkinje cell antibody (anti-Yo) has been
      found. Most patients, however, have limited oncologic disease at the time of
      onset of neurologic symptoms. We describe 2 cases of PCD due to tubal cancer with
      anti-Yo antibody. The onset of PCD occurred 4 and 14 months before the detection
      of cancer, respectively, and the presence of anti-Yo antibody facilitated early
      laparotomy in both cases. These patients, whose neurologic symptoms have not
      progressed, have survived without evidence of disease for 81 and 30 months since
      surgery, respectively. The presence of the anti-Yo antibody in patients with PCD
      warrants an aggressive approach to diagnosis and treatment of the underlying
      gynecologic cancer.

PMID- 9517811
TI  - A reexamination of the concurrent discrimination learning task: the importance of
      anterior inferotemporal cortex, area TE.
AB  - For 30 years, the concurrent discrimination learning task has figured prominently
      in studies used to determine the effects of medial temporal lobe damage in
      monkeys. However, the findings from these studies have been contradictory. We
      explored the contribution to concurrent discrimination performance of inadvertent
      damage to area TE by reexamining the behavioral data and histological material
      from monkeys with medial temporal lobe lesions previously tested in our
      laboratory. The amount of inadvertent damage to area TE was more predictive of
      impaired performance on the concurrent discrimination learning task than was the
      amount of damage to any medial temporal lobe structure, including the perirhinal
      cortex. These findings resolve earlier inconsistent findings regarding the
      concurrent discrimination learning task by demonstrating that performance on this
      task depends on area TE and not on perirhinal cortex or other medial temporal
      lobe structures.

PMID- 9517812
TI  - Learning and transfer of object-reward associations and the role of the
      perirhinal cortex.
AB  - Perirhinal cortex ablation has previously been shown only to impair new
      postoperative object discrimination learning with large stimulus set sizes (> or
      = 40 problems). In this study, 3 cynomolgus monkeys (Macaca fascicularis) with
      bilateral perirhinal cortex ablations were impaired relative to 3 normal controls
      on concurrent discrimination learning tasks with only 10 problems with the
      objects presented in different orientations in each trial to increase the demands
      placed on object identification. This supports the hypothesis that perirhinal
      cortex damage impairs the ability to identify multiple individual objects. Fewer
      errors were made to digitized images of objects than toward real objects. Both
      groups subsequently transferred specific object-reward associations from real
      objects to digitized images of the respective objects and vice versa, providing
      evidence that cynomolgus monkeys can recognize photographic representations of
      objects with experience.

PMID- 9517813
TI  - Relationships between dishabituation, sensitization, and inhibition of the gill-
      and siphon-withdrawal reflex in Aplysia californica: effects of response measure,
      test time, and training stimulus.
AB  - Previous studies have raised questions about the relationships between
      habituation, dishabituation, sensitization, and inhibition of reflex responses.
      To explore this issue further, a systematic study of these simple forms of
      learning was carried out in unrestrained Aplysia in which the amplitude as well
      as the duration of both the gill- and siphon-withdrawal reflexes were measured
      after either tailshock or mantle shock. The results suggest that transient reflex
      inhibition is not an invariant effect of noxious stimulation but depends instead
      on the response measure, test time, and type of noxious stimulus. Furthermore,
      the results suggest that dishabituation and sensitization may not involve
      different processes at the behavioral level; rather the observed differences
      between them may be due largely to an interaction between habituation and
      inhibition.

PMID- 9517814
TI  - Effects of thalamic and olfactory cortical lesions on continuous olfactory
      delayed nonmatching-to-sample and olfactory discrimination in rats (Rattus
      norvegicus).
AB  - We conducted 2 studies to determine the importance of several brain systems for
      remembering odorants in a go/no-go delayed nonmatching-to-sample (DNMTS) task. In
      Experiment 1, impairments were observed for lesions of pyriform cortex or (to a
      lesser extent) the lateral internal medullary lamina of thalamus. Lesions of the
      entorhinal cortex or the mediodorsal (MDn) or the paracentral and centrolateral
      (PC-CL) thalamic nuclei did not affect DNMTS. In Experiment 2, an impairment
      comparable to the pyriform lesion was observed for a lesion of the intralaminar
      nuclei (PC-CL plus the central medial nucleus) but not for a larger lesion of
      MDn. None of the lesions in either study affected the ability to learn a 2-choice
      odor discrimination using go/no-go procedures comparable with the DNMTS task.

PMID- 9517815
TI  - Thalamic amnesia reconsidered: excitotoxic lesions of the intralaminar nuclei,
      but not the mediodorsal nucleus, disrupt place delayed matching-to-sample
      performance in rats (Rattus norvegicus).
AB  - Rats with large thalamic lesions affecting the mediodorsal (MDn) and intralaminar
      (ILn) nuclei are impaired performing delayed matching to sample tasks (DMTS). To
      determine the neurological basis of this deficit, we trained rats to perform a
      place DMTS task and then compared the effects of excitotoxic lesions of the MDn,
      the ILn, and the lateral internal medullary lamina (L-IML). The MDn lesion had
      little effect. The ILn group was significantly impaired throughout 8 months of
      training. The L-IML group exhibited an intermediate level of impairment. Varying
      the sample response requirement, retention intervals, and trial-to-trial
      congruence in the side reinforced, had predicted effects, as did variations in
      response latency. However, none of these factors interacted with the treatment
      effects. These findings indicate that DMTS performance is disrupted by lesions of
      the ILn but not the MDn.

PMID- 9517816
TI  - Effects of hippocampal and parietal cortex lesions on the processing of multiple
      object scenes.
AB  - Rats were taught 1 of 3 types of multiple-object scene discrimination.
      Manipulations included either replacing (object based), displacing (space based),
      or replacing and displacing (object/space based) 1 object in the scene. Once
      trained, rats received hippocampal, parietal cortex, or cortical control lesions
      and then were retested. Parietal cortex- and hippocampal-lesioned rats displayed
      deficits on both the space and object/space tasks but not the object task. The
      hippocampal-lesioned group's deficit on the object/space task was only transient,
      whereas the impairments of the parietal cortex-lesioned rats were stable for both
      tasks. The parietal cortex-lesioned rats sustained difficulty with the
      object/space task may indicate an inability to switch cognitive strategies.

PMID- 9517818
TI  - Prefrontal cortex and caudate nucleus in conditional associative learning:
      dissociated effects of selective brain lesions in rats.
AB  - Rats with lesions to prefrontal cortex (PFC) or caudate nucleus (CN) were
      compared on tests of conditional associative learning (CAL) that placed varying
      demands on conditional rule learning and working-with-memory operations that are
      essential for response selection. Damage to either structure impaired
      performance, but the respective deficits resulted from disruption of different
      processes. CN lesions produced a consistent learning deficit that was thought to
      reflect a basic impairment in forming stimulus-response (S-R) associations. The
      behavior of PFC rats was more variable and depended on task requirements. When S
      R learning or response selection was relatively easy, the PFC was not critical.
      However, when either component was made more difficult, thus requiring the
      contribution of strategic processes, PFC damage produced profound impairments. In
      addition to clarifying the roles of the PFC and CN in CAL, the results provide
      further evidence that multiple brain regions participate in relatively simple
      behavioral tasks and that their respective contributions can be dissociated.

PMID- 9517819
TI  - Bilateral 6-hydroxydopamine lesion in the dopaminergic A8 cell group produces
      long-lasting deficits in motor programming of cats.
AB  - The effects of a small 6-hydroxydopamine lesion in the A8 cell group were studied
      in cats (N = 8) trained to walk on a treadmill. This setup allows the assessment
      of subtle changes in motor programming. The lesion produced long-lasting effects:
      (a) a decreased ability to switch arbitrarily motor patterns; (b) an increased
      ability to switch motor patterns with the help of stimuli provided by the
      apparatus; (c) alterations in the sequential patterning of motor behavior and in
      the kinetic melody of movements. It is suggested that the lesion produced a
      hypofunction of A9 cells that is compensated by a hyperfunction of A10 cells. It
      is concluded that subtle lesions in the A8 cell group produce long-lasting
      deficits in motor programming, implying that degeneration of this dopaminergic
      cell group may contribute to symptoms seen in Parkinson's disease.

PMID- 9517817
TI  - Lateralized changes in tympanic membrane temperature in relation to different
      cognitive tasks in chimpanzees (Pan troglodytes).
AB  - Lateralized changes in tympanic membrane (TM) temperature were assessed in
      chimpanzees. Subjects were engaged in 1 of 3 different cognitive tasks, including
      matching-to-sample, visual-spatial discrimination, and a motor task. During
      execution of each task, TM temperatures were taken from each ear over a 20-min
      time period. The TM temperatures at each time interval were subtracted from a
      baseline measure to assess relative change in blood flow. For the matching-to
      sample and visual-spatial discrimination tasks, significant lateralized changes
      in TM temperature were found, with left-ear temperature increasing and right-ear
      temperature decreasing. No laterality effects were found for the motor or control
      tasks. These data provide the first evidence of laterality in physiological
      functioning in chimpanzees and suggest that transient asymmetries in cognitive
      functions are associated with changes in cerebral blood flow as assessed by TM
      temperature change.

PMID- 9517820
TI  - Adult rats stressed as neonates show exaggerated behavioral responses to both
      pharmacological and environmental challenges.
AB  - Adult rats that were isolated from the mother and nest for 1 hr per day from
      Postnatal Day 2 to 9 were studied. Controls consisted of handled littermates as
      well as separate litters that were never handled. As adults, animals were given
      either a pharmacological challenge (1.0 or 2.0 mg/kg amphetamine) or an
      environmental challenge (restraint). Previously isolated animals demonstrated
      increased activity compared to controls at both drug doses. Similarly, isolated
      animals manifested exaggerated inhibition of activity after restraint. Previously
      isolated animals usually did not show differences compared to controls under
      baseline conditions (saline injection or no restraint). The neuroplastic changes
      that result from the neonatal experience are long lasting and appear when the
      system is challenged.

PMID- 9517821
TI  - A sensory-enhanced context facilitates learning and multiple measures of
      unconditioned stimulus processing in the preweanling rat.
AB  - This study tested the hypothesis that increased processing or efficacy of the
      unconditioned stimulus (US) contributes to the facilitation of trace conditioning
      that occurs when preweanling rats are conditioned in a novel sensory-rich
      context. Experiment 1 extended previous findings (D. L. McKinzie & N. E. Spear,
      1995) of facilitated acoustic trace conditioning in the 17-day-old rat in a
      sensory-enhanced versus a home odor context. In the enhanced or more familiar
      context, Experiment 2 tested rats of this age for degree of spontaneous locomotor
      activity and ultrasonic vocalizations, activity and ultrasounding in response to
      shock, and the acoustic startle reflex. The enhanced context resulted in a
      greater overall activity response to shock, increased ultrasounding to discrete
      shocks, and a sensitized latency to startle. The results suggest that enhanced US
      processing in a sensory-rich context is a likely contributor to its facilitative
      effect on infant learning.

PMID- 9517822
TI  - Sex differences in the effects of frontal cortex injury: role of differential
      hormonal experience in early development.
AB  - The extent to which sex differences in the behavioral effects of frontal injury
      in the adult rat can be attributed to differential exposure to testosterone (T)
      during development was investigated. The effects of these factors on brain weight
      and relative brain size were also examined. At birth, males were gonadectomized
      (GDX) or not and females were given T or oil injections. In adulthood, all
      animals were GDX or sham-operated and received either bilateral aspiration
      lesions of the medial frontal cortex or a sham operation. Rats were tested on the
      Morris water maze task, the radial arm maze (RAM), and the landmark water task.
      The effects of frontal injury on performance of the Morris water maze task were
      greater in rats not exposed to T at birth, there was no effect of neonatal T
      exposure on performance on the RAM, and on the landmark water task there was a
      complicated interaction of sex and neonatal T exposure in rats with frontal
      injury.

PMID- 9517823
TI  - Estrogen and sequential movement.
AB  - Normal movement depends in part on the brain's ability to produce and use
      dopamine, which regulates basal ganglia function. Behavioral, neuroanatomical,
      and neurophysiological data suggest that the basal ganglia are critical for the
      performance of sequential movement. Dopaminergic function is modulated by
      estrogen in animals and in humans. To test the hypothesis that estrogen modulates
      sequential movement, this study measured the reaction time (RT) and movement time
      (MT) of 15 women and 10 men in a choice RT task with sequential responses. Higher
      levels of estradiol in women's blood were associated with faster total movement
      time (RT plus MT). Testosterone levels in women's blood were not associated with
      keypressing performance. Hormone levels in men's blood were unrelated to
      keypressing performance. These results suggest that women's motor performance was
      affected by hormone levels, and that estrogen may interact with dopaminergic
      function in women.

PMID- 9517824
TI  - Ibotenic acid lesions of the parabrachial nucleus and conditioned taste aversion:
      further evidence for an associative deficit in rats.
AB  - Rats with extensive ibotenic acid lesions centered in the gustatory zone of the
      pontine parabrachial nucleus (PBN) failed to acquire a conditioned taste aversion
      (CTA) induced by lithium chloride (LiCl) toxicosis (Experiments 1 and 4). This
      deficit cannot be explained as an inability to either perceive or process
      gustatory information because lesioned rats that failed to acquire a CTA readily
      acquired a conditioned flavor preference (Experiment 2). Similarly, the CTA
      deficit cannot be attributed to an inability to experience or process visceral
      input because PBN-lesioned rats that failed to acquire a CTA successfully learned
      an aversion to a trigeminal stimulus, capsaicin, when paired with LiCl-induced
      illness (Experiment 3). This pattern of results supports the view that cell
      bodies within the PBN are essential for the associative processes that govern CTA
      learning.

PMID- 9517826
TI  - Benzodiazepine-induced amnesia in rats: reinstatement of conditioned performance
      by noxious stimulation on test.
AB  - A benzodiazepine (midazolam), injected either systemically or directly into the
      basolateral amygdala (BLA), differentially affected the acquisition of fear
      responses to a shocked context: Administration of the drug before conditioning
      impaired subsequent freezing to the context but spared analgesic responses in
      rats tested there for sensitivity to formalin pain. Moreover, the pain test not
      only revealed evidence for analgesic responses but also served to reinstate
      conditioned freezing that was otherwise absent in rats conditioned under
      midazolam. The results were interpreted as showing that the presence of noxious
      stimulation on test serves either (a) to assist in retrieval of the context-shock
      association whose storage had been modified by midazolam's action in the BLA, or
      (b) to enable performance of the context-shock association whose affective
      properties had been blocked by midazolam's action in the BLA.

PMID- 9517825
TI  - Long-term memory retrieval deficits of learned taste aversions are ameliorated by
      cortical fetal brain implants.
AB  - In this study, the effects that fetal brain implants have on the ability to
      retrieve the memory for a previously acquired conditioned taste aversion (CTA) in
      insular cortex (IC) lesioned rats were tested. Several groups of rats were
      trained for a CTA, were lesioned in the IC 4 days later, were implanted with
      different fetal cortical tissues, were treated or untreated with nerve growth
      factor (NGF), and then were tested for recall either 15 or 45 days later. Rats
      were then retrained and tested with a different taste and in the inhibitory
      avoidance (IA) task. All implanted animals recovered the retrieval of CTAs
      learned before IC lesions; however, only the homotopic IC implants at 45 days or
      NGF supplemented at 15 days induced recovery of the ability to learn CTA. The
      latter effect was also true for IA learning. The results suggest that the brain
      mechanisms for recovery of memory functions are different from those of learning
      abilities.

PMID- 9517827
TI  - Learned tolerance to ethanol-induced c-Fos expression in rats.
AB  - With c-Fos immunoreactivity as a marker for neural activity, we examined whether
      environmental cues associated with ethanol injection influence the expression of
      tolerance to ethanol-induced c-Fos activation. Over 24 training days, male Long
      Evans rats received ethanol injection (2.5 g/kg) in one environment and saline
      injection in a different environment. Relative to rats that received ethanol for
      the first time, ethanol-induced c-Fos expression in the paraventricular nucleus
      of the hypothalamus (PVN) and the locus coeruleus (LC) was significantly reduced
      in rats that had received multiple prior ethanol administrations. However,
      tolerance was partially reversed when ethanol was given in the saline-paired,
      rather than the ethanol-paired, environment. Results suggest that tolerance to
      ethanol, as indexed by c-Fos expression in the PVN and the LC, is mediated in
      part by Pavlovian conditioned responses to cues that predict ethanol
      administration.

PMID- 9517828
TI  - Role of frontal cortex in social odor discrimination and scent-marking in female
      golden hamsters (Mesocricetus auratus).
AB  - Orbital/agranular insular (ORB/AI) cortex has been implicated in traditional
      olfactory learning tasks and social behavior but its precise role in
      discriminating-learning social odors is not known. Female golden hamsters
      received aspiration lesions of ORB/AI or dorsomedial (DM) frontal cortex and were
      tested for their ability to (a) discriminate between odors of individual males in
      a habituation-discrimination task, (b) show preferences for male over female
      odors, and (c) scent-mark in response to male odors. Lesioned females readily
      discriminated between scents of individual males. Neither lesion altered female
      preferences for male odors. Females with DM lesions showed increased levels of
      scent marking to male odors, but those with ORB/AI cortex lesions did not differ
      from controls. Thus, ORB/AI cortex does not appear to be critical for
      discrimination of odors of individuals or sex or for scent-marking responses
      based on these discriminations.

PMID- 9517829
TI  - Habituation of oral responding in adult rats.
AB  - The effects of repeated oral stimulation on ingestive responding were
      investigated in adult rats. A series of brief intraoral infusions of flavored
      diet was delivered to female rats once every minute through an oral cannula. When
      the flavor of the infused diet remained constant, significant decreases in
      mouthing behavior were observed by the end of testing, whereas switching the
      flavor of the diet during testing resulted in enhanced responding and infusions
      delivered through gastric cannulas produced minimal effects. Patterns of oral
      responding were also similar in food-restricted rats. These patterns of
      responding suggest that adult rats habituate to oral stimulation. Finally, oral
      habituation led to decreased ingestion, whereas gastric infusions had minimal
      effects. Thus, oral habituation may represent a mechanism influencing intake in
      rats at all ages.

PMID- 9517830
TI  - Treadmill performance of mice with cerebellar lesions: 1. Purkinje cell
      degeneration mutant mice.
AB  - The purpose of this study was to evaluate the sensorimotor skills of a
      spontaneous mouse mutant, Purkinje cell degeneration (PCD), marked by selective
      cerebellar cortical atrophy on a treadmill activated at 1 of 2 speeds and at 1 of
      3 slopes, requiring forward movements to avoid footshocks. There was no
      difference in latencies before falling from the belt between PCD mutants and
      controls during acquisition. However, PCD mutants were impaired on the fast
      treadmill during retention, implicating the cerebellum in the memory of a motor
      skill. During acquisition of the slow treadmill task at the 2 lowest slopes of
      inclination, PCD mutants spent more time walking than controls, an indication of
      a decreased ability of coordinating whole body movements. The same pattern of
      higher walking time on the slow treadmill in PCD mutants was evident during
      retention. These results indicate that the cerebellar cortex is involved in the
      acquisition and the retention of a task requiring equilibrium.

PMID- 9517831
TI  - Systemic and intracerebroventricular injections of vasotocin inhibit appetitive
      and consummatory components of male sexual behavior in Japanese quail.
AB  - The authors investigated the behavioral actions of vasotocin (VT) in castrated
      testosterone-treated male Japanese quail. The appetitive and consummatory
      components of sexual behavior as well as the occurrence frequency of crows were
      inhibited, in a dose-dependent manner, by injections of VT. The authors observed
      opposite effects after injection of the V1 receptor antagonist, dPTyr(Me)AVP.
      Lower doses of VT were more active after central than after systemic injection,
      and effects of systemic injections of VT were blocked by a central injection of
      dPTyr(Me)AVP. The behavioral inhibition was associated with a modified diuresis
      after systemic but not central injection. These results provide direct evidence
      that VT affects male sexual behavior in quail by a direct action on the brain
      independent of its peripheral action on diuresis.

PMID- 9517832
TI  - Individual differences in freezing and cortisol in infant and mother rhesus
      monkeys.
AB  - Freezing is an adaptive defensive behavior that is expressed in response to an
      imminent threat. In prior studies with rhesus monkeys, stable individual
      differences in animals' propensities to freeze have been demonstrated. To
      understand the factors associated with these individual differences, freezing
      behavior was examined in infant rhesus monkeys and their mothers, in conjunction
      with levels of the stress-related hormone cortisol. In both mothers and infants,
      basal cortisol levels were positively correlated with freezing duration.
      Additionally, the number of offspring a mother had was negatively correlated with
      her infant's cortisol level. These findings suggest a link between basal cortisol
      levels and an animal's propensity to freeze, as well as a mechanism by which
      maternal experience may affect infants' cortisol levels.

PMID- 9517833
TI  - Neurotoxic hippocampal lesions fail to impair reinstatement of an appetitively
      conditioned response.
AB  - Rats with ibotenate lesions of the hippocampus (HPC) and nonlesioned rats were
      trained with a Pavlovian appetitive conditioning procedure in which a visual
      conditioned stimulus (CS) was first paired with a food unconditioned stimulus
      (US) and then repeatedly presented in the absence of the food US. After
      extinction of the conditioned response (CR), half of the rats received
      presentations of the food US and half did not. On a final test of responding to
      the visual CS, rats that received the postextinction US presentations showed
      higher levels of conditioned responding than the rats that did not. This
      reinstatement of CRs was not affected by the HPC lesions, which nevertheless
      impaired performance on a water maze task known to be sensitive to HPC damage.
      These data are in contrast to those of A. Wilson, D. C. Brooks, and M. E. Bouton
      (1995), who found that lesions of the fornix abolished reinstatement of
      aversively conditioned behavior.

PMID- 9517834
TI  - Differential expression of the metabotropic glutamate receptor mGluR1alpha by
      neurons and axons in the cochlear nucleus: in situ hybridization and
      immunohistochemistry.
AB  - mGluR1alpha is a metabotropic glutamate receptor involved in synaptic
      modifiability. A differential expression in specific neuronal types could reflect
      their different connections and response properties in central auditory
      processing. Using in situ hybridization and immunohistochemistry, we studied
      mGluR1alpha receptor expression throughout the cochlear nucleus. Robust labeling
      occurred in the dorsal cochlear nucleus and small cell shell, with less in the
      ventral cochlear nucleus. Among the most intensely labeled were the granule cells
      of the small cell shell. In the dorsal cochlear nucleus, most cell types
      expressed message and receptor protein, except granule cells. High levels of
      receptor were expressed by corn cells and cartwheel cells. The terminal dendrites
      and synaptic spines of cartwheel and fusiform cells contained receptor protein in
      the molecular layer, where they could synapse with parallel fibers. Fusiform
      dendrites also expressed mRNA for mGluR1alpha. The basal dendrites of fusiform
      cells contained receptor protein in the region where they receive cochlear nerve
      synapses. Immunostaining of terminal axons was prominent in the molecular layer
      and the small cell shell, where they were associated with synaptic nests,
      structures thought to provide long-term changes in excitability. Differential
      expression levels may reflect different functional requirements of specific cell
      types, including inhibitory interneurons, like corn cells and cartwheel cells,
      and excitatory interneurons, like granule cells in the small cell shell, which
      may participate in local circuits involved in modulatory or gating functions,
      such as stimulus enhancement or suppression. In presynaptic axons, mGluR1alpha
      may relate to the long-term signaling requirements of their modulatory functions.

PMID- 9517835
TI  - Synapse-specific accumulation of lithium in intracellular microdomains: a model
      for uncoupling coincidence detection in the brain.
AB  - Lithium's therapeutic specificity for the treatment of bipolar disorder may be
      attributable in part to an ability to target sites where there are high levels of
      synaptic activity. We show that glutamate receptors expressed in oocytes are
      highly permeable to lithium. Mathematical simulations of Li+ diffusion in mature
      dendritic spines suggest that in the presence of 1 mM extracellular lithium one
      synaptic current can increase Li+ concentration in the spine head by 4 mM with a
      decay time constant of about 15-20 ms. Two or more current spikes will produce
      oscillations between 6 and 8 mM or potentially higher. These results predict that
      the local intracellular lithium in dendritic spines can rise to high enough
      levels to uncouple second messenger mechanisms of coincidence detection.

PMID- 9517836
TI  - Effects of the substituted (S)-3-phenylpiperidine (-)-OSU6162 on PET measurements
      in subhuman primates: evidence for tone-dependent normalization of striatal
      dopaminergic activity.
AB  - (-)-OSU6162 is a substituted (S)-3-phenylpiperidine derivative which exhibits
      some affinity to the dopamine D2 receptor family. In vivo, the compound displays
      a unique normalizing profile on psychomotor activity by an intriguing mixture of
      stimulatory and inhibitory properties. In the present investigation, some of the
      effects of (-)-OSU6162 on central dopaminergic function were studied by positron
      emission tomography (PET) and L-[11C]DOPA in anaesthetized female rhesus monkeys.
      (-)-OSU6162 displayed a dopaminergic tone-dependent effect with a reduction in
      the striatal L-[11C]DOPA influx rate in monkeys with high baseline values and an
      increased striatal L-[11C]DOPA influx rate in animals with low baseline values.
      Infusion of (-)-OSU6162 for a whole day resulted in a stable effect with no
      evidence of tolerance. (-)-OSU6162 also stabilized dopaminergic function by
      attenuating the upregulation of the striatal L-[11C]DOPA influx rate which has
      previously been shown to occur following 6R-BH4 or 6R-BH4 + L-tyrosine infusions.
      This "Protean" effect of (-)-OSU6162 on the striatal dopaminergic function
      corresponds to previous behavioral observations in intact animals and
      demonstrates a true functional correlation to the measures obtained with L
      [11C]DOPA and PET. The normalizing and stabilizing profile of (-)-OSU6162 should
      be of value in treating a variety of disorders where an underlying dysregulation
      or disruption of dopaminergic function can be assumed.

PMID- 9517837
TI  - Preserved induction of long-term potentiation in the stratum radiatum in the CA1
      field of hippocampal slices from transgenic mice overexpressing ornithine
      decarboxylase and overproducing putrescine.
AB  - The role of putrescine in synaptic neurotransmission and plasticity was studied
      using transgenic mice overexpressing ornithine decarboxylase (ODC), a polyamine
      synthesizing enzyme. Transgenic mice were produced using the standard
      microinjection technique leading to elevated levels of putrescine in the
      periphery and in the brain. The experiments investigated whether or not ODC mice
      with elevated levels of putrescine show alterations in synaptic transmission and
      induction of long-term potentiation in the CA1 field of the hippocampus in vitro.
      Our results indicated that (1) putrescine levels in brain slices of the
      transgenic mice were more than ten times higher than those in fresh slices of
      control mice, although the absolute levels of putrescine and spermine decreased
      (by 15 and 40%, respectively) after 3-6 h incubation in vitro, while the levels
      of spermidine slightly increased (by 10%), (2) the excitatory synaptic response
      waveforms were wider (an increased half-width), and paired-pulse facilitation was
      somewhat reduced in ODC mice as compared to controls, and (3) potentiation of
      excitatory synaptic responses (measured 30-45 min after theta burst stimulation)
      did not differ between ODC and control mice. These results indicate that synaptic
      transmission is affected, but synaptic plasticity in the field CA1 assessed in
      vitro is not changed by elevated levels of intracellular putrescine.

PMID- 9517838
TI  - Differential modulation of hippocampal signal transfer by tuberomammillary
      nucleus stimulation in freely moving rats dependent on behavioral state.
AB  - Tuberomammillary histamine neurons (TM) in the posterior hypothalamus project to
      extensive parts of the brain, including the hippocampal formation. The purpose of
      the present experiments was to investigate whether activation of the TM modulates
      signal transfer from the perforant pathway (PP) or ventral hippocampal commissure
      (VHC) to the dentate gyrus (DG) in freely moving rats. Paired pulses of
      electrical stimulation were delivered to PP or VHC, and evoked field potentials
      (fEPSPs and pop spikes) were recorded in the DG. Before activating PP or VHC, the
      TM was triggered by electrical stimulation. Experimentation was performed during
      four behavioral conditions: exploration, grooming, awake immobility, and slow
      wave sleep. Electrical activation of the TM was found to modify dentate fEPSPs
      evoked by PP or VHC stimulation without generating a field potential by itself.
      Train stimulation of the TM (100 Hz, 500 ms) preceding paired pulses on the
      hippocampus by 50 ms decreased dentate fEPSPs in dependence of the ongoing
      behavior and the pathway stimulated. During exploration but not consummatory
      behavior, the PP signal was reduced when preceded by TM stimulation; during
      consummatory behavior but not exploration, the VHC signal was reduced. In
      contrast to other hippocampal afferents which increase pop spikes but leave
      fEPSPs unchanged, TM stimulation decreased dentate fEPSPs without affecting pop
      spike activity. Thus, the TM-histaminergic system seems to modulate signal
      processing in the dentate gyrus in a specific way, exerting an inhibitory action
      on the entorhinal input only during learning-related exploratory behavior.

PMID- 9517839
TI  - Effects of risperidone and haloperidol on tachykinin and opioid precursor peptide
      mRNA levels in the caudate-putamen and nucleus accumbens of the rat.
AB  - We investigated whether the two output pathways of the striatum are differently
      affected by the novel atypical drug risperidone and the conventional typical
      antipsychotic drug haloperidol. To this end, changes in mRNA levels of
      preproenkephalin-A, preproenkephalin-B, and preprotachykinin were determined in
      the rat striatum following chronic drug treatment for 14 days, using quantitative
      in situ hybridization. Furthermore, we studied the contribution of the dopamine
      D2 and serotonin 5-HT2A antagonist components of risperidone in establishing its
      effects on neuropeptide mRNA levels in the striatum. The results showed that both
      risperidone and haloperidol had major effects on the preproenkephalin-A mRNA and
      thus on the indirect striatal output route, whereas they had minor effects on
      preproenkephalin-B and preprotachykinin mRNA, contained by the direct output
      route. When both drugs were administered in the same dose, preproenkephalin-A
      mRNA was much more elevated by haloperidol than by risperidone. However, when
      doses of risperidone and haloperidol were modified to attain comparable dopamine
      D2 receptor occupancy, the drugs had comparable effects on preproenkephalin-A
      mRNA levels. It was further found that 5-HT2A/C receptor blockade with ritanserin
      had only modest effects on preproenkephalin-B and preprotachykinin mRNA levels
      and did not affect preproenkephalin-A mRNA levels. We conclude that risperidone
      and haloperidol, administered in the same dose, differently affect the striatal
      output routes. Furthermore, the results suggest that the effects of risperidone
      on neuropeptide mRNA levels are fully accounted for by its D2 antagonism and that
      no indication exists for a role of 5-HT2A receptor blockade in this action.

PMID- 9517840
TI  - Basal and stimulated extracellular serotonin concentration in the brain of rats
      with altered serotonin uptake.
AB  - We examined the relationship between the density of serotonergic (5
      hydroxytryptamine [5-HT]) uptake sites and extracellular 5-HT concentration in
      the rat brain using microdialysis with two different models, lesions with 5,7
      dihydroxytryptamine (50 microg in the dorsal raphe nucleus (DRN) 15 days before)
      and sublines of rats genetically selected displaying extreme values of platelet 5
      HT uptake. Compared to controls, lesioned rats had a reduced cortical
      concentration of 5-hydroxyindoles (45%), unchanged basal extracellular 5-HT in
      the DRN and ventral hippocampus (VHPC), and reduced basal 5-hydroxyindoleacetic
      acid (5-HIAA) concentrations (46%, DRN; 22%, VHPC). Yet the perfusion of 100
      mmol/L KCl or 1 micromol/L citalopram elevated dialysate 5-HT significantly more
      in the DRN and VHPC of controls. In genetically selected rats, platelet 5-HT
      content and uptake were highly correlated (r2 = 0.9145). Baseline dialysate 5-HT
      (VHPC) was not different between high and low 5-HT rats and from normal Wistar
      rats. However, KCl or citalopram perfusion increased dialysate 5-HT significantly
      more in high 5-HT than in low 5-HT rats, and the former displayed a greater in
      vivo tissue 5-HT recovery. Significant but small differences in the same
      direction were noted in [3H]citalopram binding in several brain areas, as
      measured autoradiographically. Thus, basal extracellular 5-HT (but not 5-HIAA)
      concentrations are largely independent on the density of serotonergic innervation
      and associated changes in uptake sites. However, marked differences emerge during
      axonal depolarization or reuptake blockade. The significance of these findings
      for the treatment of mood disorders in patients with neurological disorders is
      discussed.

PMID- 9517841
TI  - Studies of the biogenic amine transporters. VII. Characterization of a novel
      cocaine binding site identified with [125I]RTI-55 in membranes prepared from
      human, monkey and guinea pig caudate.
AB  - [125I]RTI-55 is a cocaine analog with high affinity for dopamine (DA) and
      serotonin (5-HT) transporters. Quantitative ligand binding studies revealed a
      novel high affinity [125I]RTI-55 binding site assayed under 5-HT transporter
      (SERT) conditions which has low affinity for almost all classic biogenic amine
      transporter ligands, including high affinity 5-HT transporter inhibitors such as
      paroxetine, but which retains high affinity for cocaine analogs. This site,
      termed SERT(site2) for its detection under 5-HT transporter conditions (not for
      an association with the SERT) occurs in monkey caudate, human caudate, and guinea
      pig caudate membranes, but not in rat caudate membranes. SERT(site2) is
      distinguished from the DA transporter (DAT) and SERT by several criteria,
      including a distinct ligand-selectivity profile, the inability to detect
      SERT(site2) in cells stably expressing the cloned human DAT, and insensitivity to
      irreversible ligands which inhibit [125I]RTI-55 binding to the DAT and SERT.
      Perhaps the most striking finding about SERT(site2) is that a wide range of
      representative antidepressant agents have very low affinity for SERT(site2). The
      affinity of cocaine for this site is not very different from the concentration
      cocaine achieves in the brain at pharmacological doses. Viewed collectively with
      the observation that ligands with high affinity for SERT(site2) are mostly
      cocaine analogs, these data lead us to speculate that actions of cocaine which
      differ from those of classic biogenic amine uptake inhibitors may be mediated in
      part via SERT(site2).

PMID- 9517842
TI  - Combined phentermine/fenfluramine administration and central serotonin neurons.

PMID- 9517843
TI  - Circumanal glands of the dog: a new classification and cell degeneration.
AB  - BACKGROUND: The circumanal glands of the dog are thought to be a glandular
      tissue, but there is some controversy as to whether they should be classified as
      exocrine or endocrine. In this study, we examined the nature of the circumanal
      glands to determine whether they should be described as exocrine, endocrine, or
      something else altogether. In addition, we investigated the cell degeneration in
      lobules of the circumanal glands in relation to the apocrine glands. METHODS:
      Light microscopic observations were made of paraffin sections stained with
      hematoxylin and eosin, and after immunohistochemical staining with antibodies
      against alpha-smooth muscle actin, keratin, filaggrin, and 3beta-hydroxysteroid
      dehydrogenase/isomerase (3beta-HSD). Samples were also examined by electron
      microscopy after fixation by aldehyde perfusion. RESULTS: The lobules of
      circumanal glands could be divided into two types on the basis of the presence or
      absence of cysts. Four layers (I-IV) were detected in the lobules with cysts. The
      outermost layer (layer I or the basal layer) consisted of flattened cells that
      contained bundles of tonofilaments and were stained immunohistochemically with
      the antibody against keratin. Layer II (the polyhedral or "spinous" layer)
      consisted of polyhedral cells that contained bundles of tonofilaments. These
      cells were connected to adjacent cells by desmosomes, interdigitations, and gap
      junctions, and they were immunopositive for keratin. A small number of polyhedral
      cells were immunopositive for 3beta-HSD. Layer III (the granular layer) was
      composed of flattened cells that contained hematoxylin-stainable granules and
      were moderately immunopositive for filaggrin. The innermost layer (layer IV or
      the horny layer) consisted of keratin. Lobules without cysts consisted only of
      layer I (the basal layer) and layer II (the polyhedral layer). Lobules of the
      circumanal glands were not directly connected to apocrine glands. Polyhedral
      cells degenerated and were phagocytosed by basal cells at a periphery of lobules.
      Then, basal cells phagocytosing degenerated polyhedral cells escaped from
      lobules, moved into the walls of apocrine glands, and, finally, dropped into the
      lumen of apocrine glands. CONCLUSIONS: Lobules of the circumanal glands have many
      characteristics of epidermis (a basal layer, a polyhedral or "spinous layer," a
      granular layer, and a horny layer) and they should not be classified as glandular
      tissue. The cysts in lobules can be interpreted as "closed hair canals." We
      suggest that steroid metabolism might occur in the polyhedral cells of the
      lobules.

PMID- 9517844
TI  - Crown morphology, enamel distribution, and enamel structure in mouse molars.
AB  - BACKGROUND: Biomolecular research and genetic manipulations have stressed the
      importance of thorough knowledge of normal organ morphology. Mouse molar teeth
      are convenient models for studying basic interactions in organ development and
      morphogenesis. The aim of the present study was to provide basic information on
      their morphology. METHODS: Intact and sectioned/ground molars of mice of various
      ages were observed with SEM. RESULTS: Enamel-free areas (EFA) were present on
      cusp tips at time of eruption. The dominating structural configuration in enamel
      was prism decussation in inner enamel and parallel prisms in outer enamel. Prism
      decussation tended to be absent at cusp ridges and in the bottom of grooves. In
      the former location, the distinction between prisms and interprism was often
      obscured in the middle enamel zone due to decreased difference in orientation of
      their crystals. A thin layer of enamel, often aprismatic, covered the distal
      aspect of cusps in maxillary molars and the mesial aspect of cusps in mandibular
      molars. The enamel abutting on EFA was often aprismatic. Aprismatic enamel
      exhibited incremental lines with a periodicity of about 1 microm and was often
      traversed by cracks. The enamel surface was porous in the bottom of grooves.
      Parts of mouse molar enamel were incompletely mineralized at the time of
      eruption. CONCLUSIONS: SEM is a convenient method for combined studies of crown
      morphology and enamel structure. Based on morphological criteria, a modification
      of the cusp nomenclature is proposed. Enamel thickness and structure in mouse
      molars show regional variations. Fundamental similarities exist between mouse
      molar cusps and mouse incisors. Mouse molar enamel undergoes posteruptive
      maturation.

PMID- 9517845
TI  - Distribution of collagens and glycosaminoglycans in the joint capsule of the
      proximal interphalangeal joint of the human finger.
AB  - BACKGROUND: The capsule of the proximal interphalangeal joint consists of the
      central slip of the extensor tendon dorsally, the collateral ligaments at the
      sides and the palmar ligament ventrally. Fibrocartilaginous menisci have been
      reported extending into the joint cavity and the central slip has a sesamoid
      fibrocartilage articulating with the proximal phalanx. This study relates ECM
      composition in the joint capsule to function. METHODS: Each part of the capsule
      from 24 fingers amputated because of trauma, carcinoma, isthaemia, fixed-flexion
      deformities or Dupuytren's contracture, was dissected out. Sections were prepared
      for routine histology or immunolabelled with a panel of monoclonal and polyclonal
      antibodies against collagens and glycosaminoglycans using the
      avidin/biotin/peroxidase procedure. RESULTS: All parts of the capsule
      consistently labelled for types I, III and VI collagens and for dermatan and
      keratan sulphate, though labelling was more pericellular in fibrocartilaginous
      regions. In contrast, only certain regions of the capsule in some fingers
      labelled for type II collagen, chondroitin 4 or 6 sulphate. The sesamoid
      fibrocartilage in the central slip showed the greatest degree of fibrocartilage
      differentiation, especially in fixed-flexion deformity fingers, and the palmar
      ligament the least. CONCLUSIONS: The immunolabelling patterns suggest that there
      is an ordered sequence of matrix changes accompanying fibrocartilage
      differentiation. Chondroitin sulphate-containing proteoglycans accumulate first,
      and type II collagen appears later. The presence or absence of type II collagen
      probably relates to different levels of compressive loading. No
      fibrocartilaginous menisci were found in normal joints and those described
      previously are regarded as synovial folds.

PMID- 9517846
TI  - Intestinal dimensions of mice divergently selected for body weight.
AB  - BACKGROUND: Selection for body weight provides important animal models for
      studying mechanisms of growth regulation. This study evaluated growth responses
      of the gastrointestinal tract (GIT) to long-term selection of mice for high (H
      line) or low (L line) 8-week body weight as compared with random-bred controls (C
      line). METHODS: Weights and dimensions of the various parts of the GIT were
      recorded from 8-month-old mice. For light microscopic stereological analyses,
      samples were taken from eight equidistant locations covering the whole
      jejunum/ileum. Vertical sections were used for estimation of fractional volumes
      of mucosa, submucosa, and muscularis and of villous surface area density and for
      measurement of villus length. RESULTS: Differences between groups in weights and
      dimensions of the various parts of the GIT were more pronounced in the proximal
      than in the distal segments, with greatest values in H, followed by C and L mice.
      Relative to body weight, intestinal growth was similar in the three lines, except
      for significantly (P < 0.001) increased relative weights of jejunum/ ileum,
      caecum, and colon in L mice. The fractional volume of mucosa and villus length
      decreased, whereas the fractional volumes of submucosa and muscularis increased
      from the proximal to the distal locations. The absolute volume of mucosa was
      greatest in H mice, followed by C and L mice. Relative to body weight, the volume
      of mucosa was significantly (P < 0.01) greater in L mice than in the two other
      lines. The mean total villous surface area of jejunum/ileum was significantly (P
      < 0.01) different among the three lines (L line: 144 cm2; C line: 227 cm2; H
      line: 304 cm2) but proportionate to differences in metabolic body weight.
      CONCLUSIONS: Selection for body weight affected various parts of the GIT to a
      different extent. The parameters investigated changed markedly along the small
      intestine, demonstrating the need for systematic sampling. Vertical section
      stereology provides unbiased estimates of total villous surface area, which is a
      parameter of major biological significance.

PMID- 9517847
TI  - Site specificity of surfactant protein expression in airways of baboons during
      gestation.
AB  - BACKGROUND: There are disparate reports concerning the presence of surfactant
      proteins in the airways of lung. The recent finding of SP-A in tracheobronchial
      epithelium and submucosal glands in lungs from second trimester humans has
      renewed interest in potential new functions of surfactant in lung biology.
      METHODS: In situ hybridization studies were done to determine the distribution of
      SP-A, SP-B, and SP-C in baboon lung specimens from 60, 90, 120, 140, 160, and 180
      (term) days of gestation and adults. Lungs from gestation controls were obtained
      at the time of hysterotomy and adult lungs at necropsy. Riboprobes used for in
      situ hybridization contained the entire coding regions for human SP-A, SP-B, and
      SP-C. RESULTS: At 60 days, SP-C mRNA expression was evident in focal portions of
      primitive tubular epithelium but not bronchi. This distal pattern of SP-C mRNA
      expression persisted and was present in some epithelial cells of respiratory
      bronchioles at term. At 90 days, SP-A mRNA expression was present in the
      epithelium of trachea and large bronchi. SP-B mRNA expression was found in small
      bronchi, bronchioles, and distal tubular epithelium at 120 days of gestation. SP
      A mRNA bronchiolar localization became evident at 140 days of gestation and
      alveolar type 2 cellular expression at 160 days of gestation. Abrupt transitions
      of surfactant protein expression were identified (e.g., SP-A mRNA-positive cells
      in the epithelium of large bronchi with adjoining SP-B mRNA expression in small
      bronchi and bronchioles). CONCLUSIONS: Findings in the baboon indicate that there
      are well-delineated sites of surfactant protein mRNA expression in bronchial and
      bronchiolar epithelia. mRNA expressions of SP-A and SP-B are present in both
      bronchial and bronchiolar epithelium but at different sites, whereas SP-C
      expression is seen in loci of epithelial cells in respiratory bronchioles.

PMID- 9517848
TI  - Diastolic shape of the right ventricle of the heart.
AB  - BACKGROUND: Knowledge of right ventricular (RV) shape is important to the
      understanding of RV mechanical function and for the improvement of clinically
      important RV volume estimation techniques. Refinements to the simplest
      conceptions of RV shape are presented statistically here, based on a quantitative
      analysis of three-dimensional magnetic resonance (MR) images of excised lamb
      hearts. METHODS: The passive shape of the heart in six freshly excised lamb
      hearts was studied with MR imaging with independent passive pressurization of
      both ventricles. Global features of shape were assessed, including measurement of
      short-axis, cross-sectional shape parameters associated with the pinched-arc
      model. RESULTS: The slice-area x apex-base length was found to be highly
      correlated with the volume of the RV, with little sensitivity to the degree of
      filling of the ventricle or to the exact slice chosen (r = 0.987; n = 22 from
      five hearts). The RV was shown to follow a clockwise helical path around the left
      ventricle of 47 +/- 17 degrees, below the outflow tract, as seen from the apical
      view, progressing from the apex to the base. Based on the pinched-arc model, the
      anterior arc is shallower than the posterior arc, with a larger radius of
      curvature and a smaller angle between the arc and the septal axis. As the RV is
      passively filled, opposite changes in shape occur between the anterior and
      posterior regions tending to equalize their shapes. CONCLUSIONS: A high degree of
      regularity of shape does exist in the RV and, thus, can be characterized
      effectively in terms of a representative cross-sectional shape and in terms of
      the changes in that shape proceeding from the base to the apex.

PMID- 9517849
TI  - Development of the murine pulmonary vein and its relationship to the embryonic
      venous sinus.
AB  - BACKGROUND: Arguments concerning the development of the pulmonary vein, and its
      relationship to the embryonic venous sinus (sinus venosus) have continued for
      well over a century. Recently, attention has again been focused on the origin of
      the pulmonary vein. It has been suggested that, whereas the pulmonary vein
      originates from the left atrium in humans, in all other vertebrates it originates
      from the venous sinus, with subsequent transfer to the left atrium. The nature of
      this transfer has not, however, been elucidated, although there is speculation
      that the pulmonary vein is "pinched off" from the left side of the embryonic
      venous sinus. METHODS: We studied closely staged hearts of normal mouse embryos
      from a C57BL/6 x CBAcross days 10 and 11 of gestation (plug day = day 1). Two
      series of embryos were collected and fixed in 2% glutaraldehyde, 1% formaldehyde,
      buffered with 0.05 M sodium cacodylate pH 7.4 (adjusted to 330 mOsm with NaCl).
      One series was wax embedded, serially sectioned, and stained with Masson's
      trichrome. The second series was subject to microdissection and scanning electron
      microscopy. RESULTS: The atrial component of the heart tube is attached to the
      body of the embryo by reflections of the atrial myocardial wall. The attachment
      can be considered, from the outset, as the heart stalk, with the myocardial
      mesodermal connections forming a horseshoe of tissue that projects ventrally into
      the lumen of the atrium, surrounding a single evagination in the midline of the
      embryo. This heart stalk is cranial to the connections of the tributaries of the
      embryonic venous sinus and ventral to the foregut. When traced through its
      developmental stages, the evagination in the centre of the stalk, which we
      describe as the pulmonary pit, is seen to become the portal of entry for the
      developing pulmonary vein. CONCLUSIONS: The heart stalk, representing the area
      used by the pulmonary vein to gain access to the heart, and analogous to the
      dorsal mesocardium, is, from the outset, discrete from the area occupied by the
      orifices of the horns of the embryonic venous sinus. The pulmonary vein does not,
      in the mouse, develop from the tissues that form the walls of the tributaries of
      the systemic venous sinus. Comparisons with other studies suggest that early
      events in the development of the pulmonary vein are likely to be the same in all
      mammals, including humans.

PMID- 9517851
TI  - Class III beta-tubulin isotype (beta III) in the adrenal medulla: II.
      Localization in primary human pheochromocytomas.
AB  - BACKGROUND: The Class III beta-tubulin isotype (beta III) is expressed
      specifically in central and peripheral nervous system neurons at various stages
      of neuronal differentiation. We have shown previously that beta III is expressed
      in a differentiation-dependent manner in human neuroblastomas arising in the
      adrenal medulla and sympathetic chains (Katsetos et al., Clin Neuropathol 13:241
      255, 1994). The neuronal distribution of beta III in the developing and mature
      human adrenal medullae is detailed in the companion article (Katsetos et al.,
      1998A). METHODS: We have compared the localization of the neuronal beta III to S
      100 protein, a sustentacular cell marker, in 14 formalin-fixed, paraffin-embedded
      primary human pheochromocytomas of the adrenal medulla and 14 adrenocortical
      tumors (adenomas and carcinomas). RESULTS: In pheochromocytomas, beta III
      staining was present in all tumors, but the number of stained cells varied in the
      two neural neoplastic phenotypes. Although the majority of chromaffin-like cells
      were beta III-positive, there was a lack of beta III in one-third of the tumor
      cells. Compared to chromaffin-like phenotypes, neuronal (ganglion-like cells)
      were invariably beta III-positive. Stromal sustentacular cells, stromal
      fibroblasts, and tumor blood vessels were beta III-negative. Sustentacular cells
      in pheochromocytomas were S-100 protein-positive, but beta III-negative. Primary
      adrenocortical tumors were beta III-negative with the exception of rare beta III
      positive cells demonstrated in one case. CONCLUSIONS: The distribution of beta
      III in human pheochromocytomas of the adrenal gland is differentiation-dependent,
      closely recapitulating chromaffin cell and neuronal phenotypes of the normal
      adrenal medulla. Our findings indicate that beta III may be used as one of the
      adjuvant neural markers in the differential diagnosis of adrenal tumors, i.e.,
      pheochromocytoma versus adrenocortical carcinoma. The occurrence of rare beta III
      positive cells in cortical carcinomas is exceptional and probably represents the
      acquisition of a divergent neuroendocrine phenotype. The significance of the
      latter is unclear, although it may constitute a marker for malignancy.

PMID- 9517850
TI  - Class III beta-tubulin isotype (beta III) in the adrenal medulla: I. Localization
      in the developing human adrenal medulla.
AB  - BACKGROUND: The class III beta-tubulin isotype (beta III) is present in neurons
      of the central and peripheral nervous systems at the earliest stages of
      morphological differentiation (Easter et al., J Neurosci 13:285-299, 1993;
      Katsetos et al., J Neuropathol Exp Neurol 52:655-666, 1993). The localization of
      this protein by immunohistochemistry in the different cell types of the
      developing human adrenal medulla is described. METHODS: A mouse monoclonal
      antibody, TuJ1, was used to localize beta III in formalin-fixed, paraffin
      embedded sections from 18 human fetal and adult adrenal glands. Tissue sections
      were also studied with rabbit antisera recognizing either S-100 protein or glial
      fibrillary acidic protein (GFAP). RESULTS: In the developing human adrenal
      medulla, beta III immunoreactivity was maximal in migrating sympathoadrenal
      neuroblasts/immature neurons through the end of the second trimester. Clusters of
      beta III-positive migrating cells, focally forming Homer Wright rosettes, could
      be identified in a gradient of adrenocortical invasion, i.e., through the
      permanent cortex and within sinusoids of the fetal cortex en route to the
      medulla. Outside the adrenal gland, strong beta III staining was observed in
      peripheral nerve bundles, sympathetic ganglia, and paraganglia at various
      developmental stages. In adrenal glands from 23 weeks of gestation on, and
      throughout adult life, all ganglion cells were beta III immunoreactive. In
      contrast, not all chromaffin cells exhibited beta III staining, but when present,
      the staining was finely granular. Sustentacular and satellite cells,
      adrenocortical cells and other mesenchymal elements were betaIII-negative. In
      sections of fetal and adult adrenal glands, S-100 protein had a sustentacular
      localization. No GFAP staining was present in sustentacular cells from either
      fetal or adult adrenals. CONCLUSIONS: In the developing human adrenal medulla,
      there is a peak of beta III expression during the active wave of migration of
      sympathetic neuroblasts. In the mature medulla, beta III is invariably present in
      adrenergic neurons. However, not all chromaffin-like cells express beta III,
      suggesting that the presence or absence of this protein identifies two
      subpopulations of chromaffin cells.

PMID- 9517852
TI  - Class III beta-tubulin isotype (beta III) in the adrenal medulla: III.
      Differential expression of neuronal and glial antigens identifies two distinct
      populations of neuronal and glial-like (sustentacular) cells in the PC12 rat
      pheochromocytoma cell line maintained in a Gelfoam matrix system.
AB  - BACKGROUND: The rat PC12 pheochromocytoma cell line provides an established
      system for the study of neuronal differentiation. To our knowledge, glial
      differentiation has not been reported in this cell line. METHODS: We have
      studied, by immunohistochemistry and immunoblotting, the presence of neuronal
      cytoskeletal antigens [class III beta-tubulin isotype (beta III), microtubule
      associated proteins MAP2, MAP1B and tau, and different neurofilament (NF) protein
      components], and synaptophysin in comparison with the glial fibrillary acidic
      protein (GFAP) and S-100 protein in the PC12 cell line. In three different
      experiments, PC12 cells were maintained in a three-dimensional gelatin foam
      (Gelfoam) matrix system for up to 34 days with and without treatment with 1 mM
      dibutyryl cyclic (dc)AMP. Immunohistochemistry was performed on explants ranging
      from 2 to 32 days-in vitro, which were fixed in either Bouin's solution, 70%
      ethanol, or 10% neutral-buffered formalin and embedded in paraffin.
      Immunoblotting was performed on Gelfoam explants with a panel of antibodies
      against all aforementioned neuronal and glial markers. Additional immunoblot
      experiments using anti-GFAP and anti-beta III monoclonal antibodies in cell
      suspensions and homogenates from PC12 monolayer cultures were carried out to
      compare growth conditions in relation to the expression of these proteins.
      RESULTS: Beta III and MAP2 were demonstrated by immunohistochemistry and
      immunoblotting of PC12 explants maintained for up to 32 days in Gelfoam matrices
      with and without treatment with dcAMP. Intense filamentous and granular beta III
      staining of PC12 cells was observed in dcAMP-treated cultures concomitant with
      neuronal morphologic alterations (neuritogenesis and ganglionic phenotype). In
      untreated cultures, beta III staining was present in less differentiated cells,
      as well in cells undergoing neuritic development. The neuronal phenotype of PC12
      cells was confirmed by staining for MAP2, tau, and NF proteins, as well as for
      synaptophysin. The presence of beta III, MAP2, MAP1B, tau, and NF proteins was
      confirmed by immunoblotting. Clusters of GFAP-positive and S-100 protein-positive
      spindle cells, phenotypically distinct from the chromaffin-like or neuronal
      cells, were demonstrated in Gelfoam explants at 5-30 days in vitro. In 30-day-old
      cultures treated with dcAMP, there was strong filamentous GFAP and diffuse S-100
      protein staining in an increased number of sustentacular-like PC12 cells. GFAP
      staining was corroborated by immunoblotting of explants maintained under
      identical conditions in vitro. In contrast, immunoblots performed on homogenates
      from PC12 suspension and monolayer cultures were GFAP-negative. CONCLUSIONS:
      Neuronal and glial-like, presumed sustentacular, phenotypes were demonstrated in
      PC12 cells grown in Gelfoam matrices with and without treatment with dcAMP for up
      to 34 days. To our knowledge, the occurrence of glial differentiation in the PC12
      line is a hitherto unreported finding. Adult rat medullary sustentacular cells
      are known to express S-100 and GFA proteins (Suzuki and Kachi, Kaibogaku Zasshi
      Anat 70(2): 130-139, 1995), and the organ culture system employed in our study
      may well have favored this direction of differentiation.

PMID- 9517853
TI  - Lost caps in histological counting methods.
AB  - BACKGROUND: In methods with the goal of counting objects in a sectioned tissue
      volume by examining their profiles or segments in the sections, lost caps, i.e.,
      small object fragments unnoticed or missing at the section surfaces, are an
      unavoidable issue. METHODS AND RESULTS: The problem of lost caps is examined as
      it applies to four methods for counting in histological sections, the method
      usually referred to as the Abercrombie correction, the empirical method, the
      optical disector, and the physical disector. CONCLUSIONS: Lost caps are an
      insoluble problem in the Abercrombie method; the lost caps error correction
      factor should be incorporated into the Abercrombie equation. Lost caps cancel out
      in the optical disector. The empirical method logically requires, to avoid lost
      caps error, either a preliminary blind identification of object segments in the
      serial sections or identification of segments with reference to adjacent sections
      in the counting sections. Similarly, the physical disector method requires either
      a preliminary blind identification of object segments in both look-up and
      sampling sections, or use of three sections rather than two.

PMID- 9517854
TI  - What was wrong with the Abercrombie and empirical cell counting methods? A
      review.
AB  - When a tissue volume is sectioned, cells or other objects are cut into segments
      by the sectioning process. The Abercrombie and empirical methods count object
      segments in histological sections and then apply a correction formula to convert
      the segment count to object number. There has been considerable recent
      controversy over whether these methods should be abandoned (in favor of the
      disector). Although both methods appear unbiased as thought experiments on paper,
      regardless of variation in object size, shape, or orientation, in practice two
      problems are inherent in the segment-counting approach: the practical problem of
      lost caps and a conceptual flaw that becomes apparent only when a need for
      unbiased estimation of certain factors in the correction formulae is seriously
      addressed. The Abercrombie method is inevitably biased by lost caps, whereas in
      the empirical method, this potential bias can be avoided. In the Abercrombie
      formula, the relevant factor to be estimated (aside from section thickness) is H,
      mean object height in the axis perpendicular to the section plane, and in the
      empirical method, it is the ratio of segment number to object number. In both
      methods, the factor in question should be estimated from an unbiased sample of
      the total population of objects. But unbiased selection of a statistically
      adequate number of objects for this estimation constitutes an unbiased,
      statistically adequate count. Once this is done, there is no reason to complete
      the steps for estimation of the factor; the count in this specimen is finished.
      It is shown that the empirical method's serial section procedure can be used to
      estimate H. This estimate is more sensitive to lost caps than the Abercrombie
      equation, but, when the formula for H is substituted into the Abercrombie
      equation, the lost caps error disappears. However, this approach is useless, as
      making this substitution transforms the Abercrombie equation into the empirical
      method equation.

PMID- 9517855
TI  - N30 somatosensory evoked potentials in patients with unilateral Parkinson's
      disease.
AB  - The N30 component of the somatosensory evoked responses (SEP) was reported as
      absent or abnormally low in various basal ganglia disorders, including
      Parkinson's disease (PD), but its relationship to the more affected side in
      asymmetric disease has not been assessed systematically. In 14 patients with
      unilateral PD and 10 controls, SEP were performed by stimulating each upper limb
      and recording from the parietal and frontal contralateral cortex. N30 was
      symmetric in 4 patients and 4 controls; it was asymmetric in 2 controls and in 8
      patients (in 4 the responses were of lower amplitude over the affected
      hemisphere); no response was elicited in 2 patients and 4 controls. In all
      patients SEP were recorded off medication; in 9 of them the test was repeated
      following administration of L-dopa and did not show any significant changes. In
      conclusion, the N30 was asymmetric in a similar proportion of PD patients and
      controls. No correlation was found between the affected side and N30 latencies or
      amplitudes; no change was seen following L-dopa administration as well. The motor
      deficits and SEP abnormalities in PD probably reflect pathologies in different
      anatomical structures or functional circuits.

PMID- 9517856
TI  - Cortisol is higher in parkinsonism and associated with gait deficit.
AB  - INTRODUCTION: We propose an active pathogenic mechanism, involving circulating
      cortisol, in parkinsonism. MATERIALS AND METHODS: Serum cortisol was measured in
      96 subjects with idiopathic parkinsonism, 170 without, and in 17 spouses and 36
      siblings of elderly sufferers with double the number of controls, all obeying
      inclusion/exclusion criteria. RESULTS: Cortisol, adjusted for sampling time, was
      greater (17%, on average, P<0.001) in parkinsonians, but not in relatives. The
      central cortisol lowering effect of anti-muscarinics was seen (P=0.025).
      Selegiline may attenuate the disease, and parkinsonism is less frequent in
      tobacco smokers. Selegiline was associated with a lower cortisol (P=0.03):
      chronic smoking appeared (P=0.08) to be, irrespective of parkinsonism. Bowel
      stasis has been implicated in the pathogenesis: cortisol was higher in
      parkinsonians requiring laxatives (P=0.05). In controls, cortisol was lower, the
      longer the stride (P=0.02): in parkinsonians, this relationship was numerically
      reversed. A similar (P=0.01) group performance interaction was seen for
      deterioration, over 4 years, in gait. CONCLUSION: Cortisol is doing harm or
      mirroring something which is. A common pathway for neuronal protection/rescue
      emerges.

PMID- 9517857
TI  - Heart rate variability in multiple sclerosis during a stable phase.
AB  - OBJECTIVES: Multiple sclerosis (MS) frequently causes disturbances of autonomic
      functions. Cardiovascular dysautonomia has been studied by classic autonomic
      tests and, recently, by heart rate variability analysis in some isolated periods.
      Multiple authors recommended performing heart rate variability analysis with a 24
      h ECG recording to increase its sensitivity. MATERIAL AND METHODS: We analyzed
      the heart rate variability in time and frequency domains in 34 MS patients and 24
      age and sex-matched healthy control subjects, in order to evaluate the effects of
      MS on sympathetic and parasympathetic cardiovascular regulatory functions
      measured from 24-h electrocardiogram. RESULTS: Low frequency power (0.01) and low
      frequency/high frequency power (0.01) were significantly higher in multiple
      sclerosis patients independently, all together or in subgroups. Very low
      frequency (0.01) and high frequency (0.001) power were higher in less affected
      multiple sclerosis patients. Variability in time domain (0.05) were lower in most
      affected multiple sclerosis patients. CONCLUSIONS: These results suggest that
      multiple sclerosis causes cardiovascular autonomic dysregulation manifesting as
      impaired heart rate variability. This illness seems to cause an increase in
      sympathetic cardiovascular tone; the parasympathetic tone is most variable and
      depends on clinical and paraclinical findings, but the illness progression seems
      to provoke a decrease in it.

PMID- 9517858
TI  - Sensorimotor stroke; clinical features, MRI findings, and cardiac and vascular
      concomitants in 32 patients.
AB  - BACKGROUND AND PURPOSE: Sensorimotor stroke (SMS) is often included among the
      lacunar syndromes, although the underlying cause of this stroke-subtype is less
      well documented. To this end we analysed 32 patients presenting with a
      sensorimotor syndrome. METHODS: The study protocol included vascular risk
      factors, echocardiography, Doppler sonography of carotid arteries, CT scan and
      MRI of the brain. RESULTS: There were 23 men and 9 women, mean age 65.7 years.
      Hypertension was present in 28% and diabetes in 19%. In all, 63% had sensorimotor
      deficit of faciobrachiocrural areas and 37% had faciobrachial or brachiocrural
      deficits. MRI disclosed a presumably relevant infarct in 26 patients (81%); 20
      patients (62%) localized to the territory of small perforating arteries, 3
      patients (9.5%) in the internal borderzone, and 3 patients (9.5%) in cortical
      territories. Eight of 20 deep infarcts were larger than 15 mm. No hemorrhage or
      non-vascular lesion was found. A potential cardioembolic source was present in 5
      patients (16%), whereas 2 patients (6%) had an ipsilateral carotid stenosis >50%.
      CONCLUSIONS: Small vessel disease was the most likely cause in 69% of our
      patients with SMS, whereas 31% had a potential cardioembolic source, large artery
      disease or infarcts not compatible with perforating artery disease.

PMID- 9517859
TI  - Clinical changes and EEG patterns preceding the onset of periodic sharp wave
      complexes in Creutzfeldt-Jakob disease.
AB  - The conversion of EEG findings and the evolution of clinical signs was
      investigated in 7 CJD patients who underwent serial EEG recordings along the
      course. At the onset of PSWC (mean 8.7 weeks), 5 patients had already progressed
      to akinetic mutism (characterized by loss of verbal contact and directed
      responses); and a CJD-typical-movement disorder (myoclonia, exaggerated startle
      reaction or focal dyskinesia) had started in 5 patients. When akinetic mutism
      commenced (on average at 7.5 weeks), runs of frontal intermittent non-peaked
      rhythmical delta activity (FIRDA) were found in all cases. These were later
      replaced by PSWC in 6 patients (interval 1 to 3 weeks). Occurrence of PSWC was
      often negatively related to external stimuli (2 of 6 cases), and sedative
      medication (all patients tested). We conclude that the selection of EEG recording
      dates to detect PSWC in CJD-candidates should be guided by detailed information
      about movement disorders and conscious level. Regarding the short survival time
      after their onset (average 8 weeks), PSWC usually mark the terminal stage of CJD.
      To detect PSWC, especially, EEG registrations in advanced stages are often
      necessary. In earlier disease stages, FIRDA-like EEG activities should be
      regarded as compatible with this diagnosis, and encourage further EEG studies for
      the demonstration of PSWC in a more advanced stage of CJD.

PMID- 9517860
TI  - EEG findings in diabetic patients with and without retinopathy.
AB  - OBJECTIVES: We showed previously that temporal low-voltage irregular delta waves
      (TLID) on EEG are indicative of cerebrovascular dysfunction in its early stages.
      The present study was designed to determine whether the incidence of this finding
      is elevated in diabetics as compared to normal controls. METHODS: EEGs of 50
      diabetics and 50 normal controls were examined. Relationships of blood sugar
      levels, levels of HbA1C and stages of diabetic retinopathy to TLID were also
      examined. RESULTS: TLID was found in 56% of EEGs of the diabetics and in 14% of
      EEGs of the controls (P < 0.0001). The occurrence of TLID was also associated
      with the presence of diabetic retinopathy. CONCLUSIONS: Our results suggest that
      the incidence of cerebrovascular dysfunction is elevated in diabetics. Since TLID
      was associated with diabetic retinopathy, it seems possible that the TLID
      detected in diabetics might reflect certain functional changes induced by
      microangiopathy of the brain.

PMID- 9517861
TI  - Microembolic signals and intraoperative stroke in carotid endarterectomy.
AB  - OBJECTIVES: Microembolic signals (high-intensity transient signals, HITS)
      detected by means of transcranial Doppler sonography (TCD) may be relevant for
      intraoperative strokes in carotid endarterectomy (CEA). MATERIAL AND METHODS: An
      intraoperative HITS detection study was performed on 77 patients (63 men, 14
      women, mean age+/-SD, 64+/-8 years) with a total of 81 CEAs. Using the
      Scandinavian Stroke Scale the patients were clinically examined by a neurologist
      preoperatively and postoperatively within 6 h. A deterioration of the
      Scandinavian Stroke Scale was considered an intraoperative stroke if persisting
      longer than 24 h. Cranial computed tomography (CT scan) was performed
      preoperatively and 3 to 5 days postoperatively. By means of TCD total HITS count
      and mean blood velocity changes, for shunting, were recorded sufficiently in the
      middle cerebral artery in 79 CEAs. RESULTS: HITS were significantly more frequent
      in symptomatic [n = 53; HITS: median, 15 (range 1-159)] than in asymptomatic
      stenoses [n = 26; HITS: 6.5 (0-41); P < 0.001]. An intraoperative stroke in the
      hemisphere ipsilateral to the operation occurred in eight of the 81 CEAs. On
      postoperative CT scans, five of the eight strokes showed new corresponding
      territorial infarctions. In the three strokes without new CT lesions, the mean
      blood velocity changes after clamping indicated normal cerebral perfusion. Total
      HITS count was significantly higher in procedures with intraoperative strokes [n
      = 8; HITS: 33 (11-159)] than in the uncomplicated [n = 71; HITS: 10 (0-62); P =
      0.002]. No stroke occurred in 37 CEAs with 10 or less HITS, but eight in 42 CEAs
      with 11 or more HITS [P = 0.006; relative risk 1.23 (95% confidence interval:
      1.06 to 1.43)]. CONCLUSION: Microembolism seems clinically relevant in carotid
      endarterectomy. Asymptomatic patients may run a lower risk of intraoperative
      embolization.

PMID- 9517862
TI  - Does NO regulate the cerebral blood flow response in hypoxia?
AB  - OBJECTIVES: To study whether nitric oxide (NO) affects the CBF response to
      hypoxic and carbon monoxide (CO) hypoxia. MATERIAL AND METHODS: We incrementally
      reduced arterial oxygen content in rats, by decreasing the concentration of
      inspired oxygen (20 rats) or by repeated CO inhalation (20 rats), and measured
      local CBF using the hydrogen clearance method. Ten animals of each group received
      80 mg/kg NO synthase (NOS) inhibitor N-monomethyl-L-arginine intravenously prior
      to hypoxia, while 10 rats served as controls. RESULTS: Inhibition of NOS
      decreased mean CBF by 30% and increased cerebrovascular resistance by 70%. Under
      hypoxic hypoxia, mean oxygen reactivity of CBF (relative change of CBF to a
      change of arterial oxygen content) was 7.8%/vol% in control animals and 3.3%/vol%
      after NOS inhibition (P < 0.02). Under CO hypoxia, mean oxygen reactivity was
      7.3%/vol% in control animals and 5.1%/vol% after NOS inhibition (P < 0.05).
      Inhibition of NOS diminished significantly the cerebral vasodilatory response
      during hypoxic hypoxia (P < 0.05) but only to a lesser extent during CO hypoxia.
      CONCLUSION: These observations suggest that NO is involved in cerebral oxygen
      vasoreactivity, particularly in severe hypoxia.

PMID- 9517863
TI  - Extracorporeal membrane differential filtration--a new and safe method to
      optimize hemorheology in acute ischemic stroke.
AB  - OBJECTIVE: Can extracorporeal membrane differential filtration be used on
      patients with acute stroke to optimize their hemorheology without reducing the
      number of oxygen carriers (erythrocytes) - and is this form of treatment safe?
      SUBJECTS AND METHODS: In a prospective pilot study, 10 patients (67+/-4 years)
      suffering severe middle cerebral artery (MCA) stroke were treated with membrane
      differential filtration, which was first performed within 12 h following the
      onset of symptoms and repeated three times at intervals of 24 h. Hemorheological
      parameters were measured before and after each treatment session. RESULTS:
      Extracorporeal membrane differential filtration treatment immediately led to a
      significant and sustained drop in all hemorheological parameters (fibrinogen by
      54%, alpha2-macroglobulin by 76%, total cholesterol by 65%, LDL by 82%, and HDL
      by 38%). Plasma viscosity dropped from 1.3 to 1.1 mPa s, erythrocyte aggregation
      by 57%. By contrast, hematocrit and the erythrocyte count remained constant.
      Treatment had no side-effects. CONCLUSIONS: Extracorporeal membrane differential
      filtration is a safe method to optimize hemorheology in patients with acute
      ischemic stroke.

PMID- 9517865
TI  - Primary cerebellar nocardiosis and alveolar proteinosis.
AB  - We report a patient with known asymptomatic pulmonary alveolar proteinosis (PAP)
      who developed a cerebellar gait disorder and dysarthria caused by an isolated
      cerebellar nocardial abscess. To our knowledge only 1 patient with PAP and
      isolated central nervous system nocardia infection has previously been reported.
      In this early report, diagnosis was established at autopsy. In our patient the
      clinical and MRI examinations of this cerebellar abscess are described and
      specific features leading to earlier diagnosis and successful treatment are
      presented.

PMID- 9517864
TI  - Implicit and explicit learning in an auditory serial reaction time task.
AB  - OBJECTIVE: To explore the role of the motor cortex during implicit and explicit
      learning. MATERIALS AND METHODS: EEG signals were recorded from 30 channels by
      measuring task-related desynchronization (TRD) when 10 right-handed naive
      volunteers performed a variation of the serial reaction task. Stimuli, consisting
      of 4 pure tones of 500, 1000, 1500, and 2000 HZ, lasting 200 ms, were presented
      binaurally through a pair of tubephones at 60 dB with a 2-s constant
      interstimulus interval. A series of 10 repetitive tones represented the test
      sequence; the random sequence was the control. RESULTS: All subjects developed
      implicit and explicit knowledge reflected by decreased response time, increased
      accuracy, and the ability to generate the sequence. Six of 10 subjects
      demonstrated implicit learning without explicit learning during the first 3
      blocks. When subjects acquired full explicit learning, 10 Hz TRD at C3 reached a
      peak amplitude, declining thereafter. CONCLUSIONS: Properties of the sensorimotor
      cortex change during learning and these changes are independent of stimulus
      modality.

PMID- 9517866
TI  - Buspirone in primary headaches.

PMID- 9517867
TI  - Trends in mortality from major diseases in Europe, 1980-1993.
AB  - Trends in age-standardized death certification rates from all causes, coronary
      heart disease (CHD), cerebrovascular diseases, all neoplasms and lung cancer were
      analysed over the period 1980-1993 in 20 major European countries. There were
      steady and substantial declines of overall mortality in all western European
      countries for both sexes, although appreciable geographic differences persisted.
      These favourable trends reflect a decline in CHD mortality in most western
      countries, besides a persisting fall in cerebrovascular disease, and a
      substantial stability (with some decline in a few northern and central European
      countries) in cancer mortality. In contrast, in eastern European countries
      appreciable rises were registered in mortality from major causes of death
      considered for males. For females, only moderate declines were observed in
      Eastern Europe. In the early 1990s, overall mortality was 30 to 100% higher for
      males and 20 to 100% higher for females as compared to Western Europe. As
      indicated by the trends in lung cancer death rates, this reflects a major impact
      of the tobacco-related disease epidemic in subsequent cohorts, as well as more
      unfavourable lifestyle factors (i.e. aspects of diet, other environmental
      factors), and a delayed control of hypertension in Eastern Europe, together with
      a substantial excess of suicides, (road) accidents, homicides and alcohol-related
      diseases, and the delayed introduction of rational treatment for some conditions.
      An indication of reversal of mortality trends was evident in the early 1990s only
      in Poland. In conclusion, there is ample scope for intervention on avoidable
      mortality in eastern European countries.

PMID- 9517869
TI  - A mathematical model for the determination of the optimum value of the treatment
      threshold for a continuous risk factor.
AB  - Hypercholesterolemia or hypertension are continuous risk factors for coronary
      heart disease. When a preventive action is carried out against such a risk
      factor, it is necessary to specify a risk factor level value, named the treatment
      threshold, above which a subject should be treated. But a non-arbitrary
      determination of this threshold value is impossible from the epidemiological
      data. A method for the non-arbitrary determination of the treatment threshold
      value is presented, based upon mathematical modelling of the clinical and
      economics consequences of the prevention policy in the whole population. In a
      cost-effectiveness approach, the model was used to estimate the cost per coronary
      event prevented according to the threshold value for blood cholesterol. It was
      found that a minimum in this outcome proposed as the optimum treatment threshold.
      It is possible, from a public health point of view, to determine an optimum, non
      arbitrary treatment threshold value in the prevention of coronary heart disease
      with cholesterol-lowering interventions. The model proposed here could be useful
      in decision making processes.

PMID- 9517870
TI  - Prevalence, awareness, treatment, and control of hypertension in a Spanish
      population.
AB  - A cross-sectional population survey using a random, stratified sample into phases
      was conducted in order to assess the prevalence, awareness, treatment, and
      control of hypertension in Albacete (a south-eastern province in Spain) with
      248000 inhabitants over 18 years of age. The sample size was of 1322 people. Both
      systolic and diastolic BP were higher in men than in women and showed an
      increasing trend with age independently of gender. Assuming a cut-off for
      hypertension of <140/90 mm Hg and <160/95 mm Hg, we found a prevalence of
      hypertension of 32.7% and 23.1%, respectively. Overall, 56.5% of hypertensive
      subjects were aware of their condition. The degree of this awareness was
      significantly higher in women and in the elderly. The percentage of patients who
      were receiving antihypertensive treatment was 49.1%. This proportion was also
      higher among women, elderly people, and subjects living in urban areas. High BP
      was successfully controlled in 10.9% of the total hypertensive population which
      accounted for 24.4% of the treated patients. The corresponding figures for the
      <160/95 mm Hg cut-off were 38.5% and 60.6%, respectively. In the logistic
      regression model, male gender and size of the local community were significantly
      associated with a better pharmacological control of hypertension. We found a high
      prevalence of hypertension with low degree of awareness and control, despite the
      general progress made in the diagnosis and treatment of hypertension in Spain.
      Specific intervention programs are necessary to increase the extent of control of
      hypertension in our country.

PMID- 9517871
TI  - Occurrence of serologically verified Mycoplasma pneumoniae infections in Poland
      in 1970-1995.
AB  - This study analyses the numbers of serologically verified Mycoplasma pneumoniae
      infections in Poland in 1970-1995. The investigations were performed using the
      complement fixation test (CFT) with sonicated antigen in National Institute of
      Hygiene in Warsaw and since 1985 in 33 laboratories throughout the country. The
      result was accepted as positive when antibody titre was 60 or higher, or at least
      a four-fold increase in titre occurred during the illness. During these studies
      five epidemics of mycoplasmosis were noted in Poland. They occurred regularly
      every 5 years during the autumn-winter season in 1970/1971, 1975/1976, 1980/1981
      and 1985/1986. The last epidemic, which started in 1991 and culminated in 1992
      1993, seems to have inaugurated a change from epidemic to endemic occurrence of
      M. pneumoniae infection in Poland. At the peak of the epidemic, depending on the
      region of country, in 20-38% of patients with respiratory tract infection
      serological confirmation of mycoplasmosis was obtained.

PMID- 9517872
TI  - Frequency and determinants of use of antiretroviral and prophylactic therapies
      against Pneumocystis carinii Pneumonia (PCP) before AIDS diagnosis in Italy.
AB  - To determine the frequency and the determinants of use of antiretroviral drugs
      and prophylaxis for Pneumocystis carinii Pneumonia (PCP) among HIV-infected
      individuals before AIDS diagnosis, a questionnaire was sent to all physicians
      reporting at least one AIDS case during the first six months of 1994 to the
      Italian National AIDS Registry. Information on cases diagnosed between 1 January
      and 31 March 1995 was collected. Information was obtained for 878 (66.4%) of the
      1323 persons with AIDS: 447 (50.9%) had received antiretroviral drugs and 343
      (39.1%) PCP prophylaxis, whereas 303 cases (34.5%) had received both. Individuals
      who became aware of being HIV-positive shortly before AIDS diagnosis were less
      likely to have started antiretroviral therapy (adjusted odds ratio (AOR): 0.05,
      95% CI: 0.03-0.09). Homosexual men and heterosexuals were more likely to begin
      therapy (AOR: 1.40, 95% CI: 0.83-2.37 and AOR: 1.79, 95% CI: 1.05-3.05,
      respectively) compared to injecting drug users. Individuals living in Southern
      Italy and foreigners were less likely to start therapy (AOR: 0.75, 95% CI: 0.49
      1.16 and AOR: 0.40, 95% CI: 0.15-1.09, respectively) compared to those living in
      Northern Italy. Results were similar for PCP prophylaxis. Lack of awareness of
      HIV infection, HIV exposure category, and geographical area were the most
      important factors associated with treatment before AIDS diagnosis.

PMID- 9517868
TI  - A review on ethnic differences in plasma triglycerides and high-density
      lipoprotein cholesterol: is the lipid pattern the key factor for the low coronary
      heart disease rate in people of African origin?
AB  - Black people in the UK, in the Caribbean, and to a lesser extent in the USA,
      experience coronary heart disease events at different rates than white people.
      Despite having higher prevalence of hypertension, cigarette smoking and diabetes,
      black males have significantly lower coronary heart disease rates than white
      males, whereas no significant differences have been detected in females. The only
      known risk factor differences that could account for the difference in CHD rates
      are higher HDL cholesterol and lower triglycerides that are seen in blacks
      compared with whites. Obesity and, in particular abdominal obesity, seems to
      determine TG and HDL cholesterol levels: black males are less centrally obese
      than whites, while total adiposity and central distribution of fat is more
      predominant in black females compared with white females. We propose that the
      less degree of abdominal adiposity observed in black males is related with an
      increased anti-lipolytic effect of insulin, which could account for low
      triglycerides and high HDL cholesterol levels, and consequently explain the
      higher protection from coronary heart disease experienced by black males compared
      with whites and black females.

PMID- 9517873
TI  - Crohns disease in Slovakia: prevalence, socioeconomic and psychological analysis.
AB  - The need for a basic epidemiological study, according to international standards,
      of the prevalence of IBD in Slovakia was increased by the dissolution of
      Czechoslovakia. This paper presents the results of CD prevalence to 30 April 1994
      in Slovakia. To evaluate the statistical data of the prevalence of the disease
      according to age, sex, regions and districts, the authors employed the multi
      dimensional Kruskal-Wallis test and cluster analysis and determined that the
      prevalence of CD in Slovakia is 6.75/100.000 inhabitants. The distribution
      differences indicate the need for further investigations of environmental
      differences. The socio-economic and psychological evaluation of the patients
      examined revealed some interesting associations. The psychological reaction to
      the disease is neurotic and depressive and a higher occurrence of affective
      symptomatology was observed in patients with permanent partnership and with
      children. On the other hand, the educational level and knowledge concerning the
      disease on the part of the patient had a positive influence on the reaction to
      the disease.

PMID- 9517874
TI  - Prevalence of intestinal parasitosis within three population groups in La Plata,
      Argentina.
AB  - The prevalence of intestinal parasites was studied as a function of socioeconomic
      conditions within La Plata, Argentina. Age, sex, and environmental factors were
      considered. Thus, from each of three areas within the city - the first a
      'marginal' zone, the second a lower-income suburb, the third a middle-income
      urban district - 100,101, and 91 children up to 14 years old, respectively, were
      examined for intestinal parasites. Giardia lamblia was the most frequent species
      found. The respective prevalences of intestinal parasites overall (73, 54.4, and
      35.1%), of polyparasitism (61.6, 27.2, and 12.5%), and of helminthic infection
      (32, 10.9, and 0.0%) were the highest within the population group having
      significantly inferior sanitary and environmental conditions. A positive
      statistical association between the prevalence of intestinal parasitosis and age
      was observed in all three of the neighborhoods. We also noted a correspondence
      between the frequency of such infections and school attendance in the two
      suburban districts. Management practices in accordance with the specific
      characteristics of an urban environmental and sociocultural ecosystem are thus
      important for the control of intestinal-parasite infection within municipal
      populations.

PMID- 9517875
TI  - Methodological aspects of physical activity assessment in epidemiological
      studies.
AB  - A range of epidemiological studies conducted over the past decades has produced
      strong support for the view that lack of physical activity is associated with
      increased risks of several chronic diseases, such as cardiovascular disease,
      diabetes mellitus, cancer, etc. Much is still unknown about the type and degree
      of activity that is required to influence the risk of specific diseases.
      Furthermore, physical activity can act as a confounder in relationships between
      other exposure variables (e.g. diet) and disease. Thus, the measurement of
      physical activity in epidemiological studies is of great importance. The
      questionnaire is the most frequently used method in epidemiological research.
      Before using a questionnaire on a large scale, validity and reproducibility
      should be assessed in a representative population. Some practical and
      methodological aspects of physical activity validation studies are described,
      together with the possible implications of the results.

PMID- 9517876
TI  - Asymmetry correction equations for hand volume, grip and pinch strengths in
      healthy working people.
AB  - Assessments of oedema and decrease in hand strength are useful for patients with
      a hand lesion. This study examined the asymmetry of the arms and determined the
      estimates of the unknown prior to lesion values for hand volume, grip strengths
      assessed with a Jamar dynamometer (GS[J]) and a Collins dynamometer (GS[C]), and
      pinch strength with a Jamar pinch gauge (PS) in 100 healthy working people. Hand
      volume, GS(J), GS(C) and PS of the dominant hand were respectively 3.6 +/- 4.1%,
      6.6 +/- 9.2%, 11.7 +/- 11.2%, and 8.0 +/- 13.2% higher than those of the non
      dominant hand (p < 0.001). Very good estimates were obtained with the values of
      the contralateral arm for all the indices studied. The correlation coefficient
      equalled 0.95 for hand volume, 0.91 for GS(J), 0.83 for GS(C), and 0.72 for PS.
      These estimates allow us to evaluate the evolution of oedema and hand strengths
      in patients with hand injury, especially to determine whether they could return
      to work as they are mostly manual workers with demanding jobs.

PMID- 9517877
TI  - Socioeconomic variation in back and joint pain in Finland.
AB  - Differences in the prevalence of back and joint pain by occupational class and
      education were studied in surveys representative of adult Finns. The effects of
      lifestyle factors and mental distress on these differences were also analysed.
      The material comprised 3915 women and 3629 men, all occupationally active.
      Occupational class and level of education were associated with back and joint
      pain; the associations were more obvious in men than in women. Among men, the age
      adjusted odds ratio of joint pain in farmers was 3.2 (95% CI: 2.1-5.0), in manual
      workers 2.6 (1.9-3.6), in entrepreneurs 2.4 (1.5-3.7) and in lower white-collar
      workers 1.7 (1.1-2.4) as compared with upper white-collar employees. Similar odds
      ratios of back pain were 2.1 (1.6-2.9) in farmers, 1.8 (1.5-2.3) in manual
      workers, 1.7 (1.2-2.4) in entrepreneurs and 1.4 (1.1-1.7) in lower white-collar
      workers. Most of the associations persisted in multivariate analyses, in which
      height, marital status, lifestyle (smoking, leisure-time physical activity and
      body mass index (BMI)) and mental distress were considered; in these models,
      mental distress was consistently associated with pain. Back pain was associated
      with smoking in men and with BMI in women; BMI was also associated with joint
      pain in both sexes. In women, height showed an association with back pain for
      which a doctor had been consulted. Marital status, alcohol consumption, leisure
      time physical activity and the urbanization level of the community were not
      important as determinants of pain. CONCLUSION: Obvious differences occurred in
      back and joint pain by indicators of social class that were not due to
      socioeconomic differences in lifestyle, height or mental distress.

PMID- 9517878
TI  - Familial pattern of infection with hepatitis B virus among immigrating Ethiopian
      Jews in Israel.
AB  - Seventy-eight families (506 members) of recently immigrating Ethiopian Jews to
      Israel, were tested for the presence of HBV serological markers to evaluate the
      intrafamilial horizontal transmission of the virus. Eighty-four members (16.6%)
      were carriers and 20.2% were HBeAg positive, the overall infection rate was
      67.8%. In 40 families (51.3%) at least one family member was HBsAG positive, and
      in 19 families (24.4%) two or more family members were HBsAg positive. Thirty-six
      carriers (42.8%) were children under the age of 10, by one year of age 30% have
      contracted the virus, and by the age of 5 and 10 years 43.5% and 57.1% have had
      serological markers for past HBV infection, respectively. Our data correlate with
      other studies regarding the importance of horizontal spread of HBV among Sub
      Saharan Africans.

PMID- 9517879
TI  - Agreement between reported fish consumption obtained by two interviews and its
      impact on the results in a reproduction study.
AB  - In an ongoing study of the hypothesised association between consumption of fish
      contaminated with persistent organochlorine compounds and low birth weight, a
      relevant measure of exposure is the accumulated fish consumption over long time
      periods. An issue of concern in this study is the quality of the retrospective
      exposure assessments. The present investigation was undertaken to determine the
      agreement between reported fish consumption in two interviews with approximately
      one year in between. in order to evaluate its impact on the effect estimates. The
      agreement decreased with increasing retrospective time interval between interview
      and focused time period of fish consumption. Furthermore, the exposure
      assessments based on the two interviews led to considerably different effect
      estimates.

PMID- 9517881
TI  - Pica behavior associated with buprenorphine administration in the rat.

PMID- 9517880
TI  - An outbreak of Salmonella hadar associated with food consumption at a building
      site canteen.
AB  - A biphasic outbreak of gastroenteritis caused by Salmonella hadar affected
      canteen employees and workers at a construction site in central Italy in
      September 1994. There were 448 symptomatic cases, from 61 of whom group C
      Salmonella was isolated. Six cases were canteen employees. Twenty-two other
      individuals were asymptomatic excreters. There were 10 secondary cases. Working
      as a food handler at the canteen constituted an increased risk of infection,
      independently of ingestion of the food (odds ratio: 62.1; 95% confidence interval
      (CI): 9.5-406.6). Having eaten at the canteen on the 19th and 20th September was
      identified as risk factor for subjects symptomatic within 72 hours (relative risk
      (RR): 17.0, 95% CI: 2.3-124.3), and cooled meat salad was identified as the
      vehicle of infection (RR: 36.6, 95% CI: 14.3-93.8). The use of portable toilets
      was another possible route of transmission of infection for all cases (RR: 1.3,
      95% CI: 1.0-1.6). The index case was a cook who had symptoms five days before the
      peak of the outbreak. From 27 individuals both symptomatic and asymptomatic
      excreters group B, group D and not-typed Salmonellas were isolated. This study
      underlines the problem of improper food handling in salmonellosis outbreaks and
      emphasizes the role of several vehicles in the transmission of salmonellosis in a
      community.

PMID- 9517882
TI  - Mouse hepatitis virus: a durable foe.

PMID- 9517883
TI  - Animal models of muscular dystrophies.
AB  - Recent advances in molecular biology have indicated that many mutant animal
      models of muscular dystrophy share common genetic and protein abnormalities
      similar to those of the human disease. The best example is a model of Duchenne
      muscular dystrophy (DMD), the mdx mouse. Similar to dystrophic muscle in DMD
      patients, dystrophin protein is not expressed along the surface membrane, even
      though the mdx mouse has no apparent signs of muscular dysfunction. Because
      clinical and pathologic findings in the dystrophic (mxd) dog are similar to those
      in DMD patients, it also has been regarded as a good model for therapeutic
      trials. The best known and most extensively studied dy+dy+ mouse lacks merosin
      (laminin alpha2), which is one subunit of a basement membrane protein, laminin.
      Because approximately half of all patients with the classical form of congenital
      muscular dystrophy also lack merosin, availability of this animal has revived
      interest in the study of the pathologic mechanism of fiber necrosis resulting
      from this membrane defect. The dystrophic hamster is a model of limb-girdle
      muscular dystrophy with sarcoglycan deficiency in which one of the dystrophin
      associated glycoproteins, delta-sarcoglycan, is defective. Because these animal
      models have common protein and genetic defects similar to those seen in people
      with muscular dystrophies, they have been widely used to examine the
      effectiveness of gene therapy and the administration of pharmacologic and trophic
      factors.

PMID- 9517884
TI  - Clinical disease associated with simian agent 8 infection in the baboon.
AB  - Simian agent 8 (SA8) is an alphaherpesvirus that was first reported as a
      spontaneous natural infection in a captive baboon colony in 1988. It was first
      isolated from an African vervet monkey in 1958 and was classified as a simian
      agent. Simian agent 8 was later isolated from a baboon rectal swab specimen in
      1969 and from an oral lesion in a vervet monkey in 1972. Restriction endonuclease
      analysis was used to identify the virus as SA8. In a 1-year period, 70 baboons
      housed in two outside 6-acre breeding corrals developed lesions principally on
      the genitalia and oral cavity. The incidence was the same for males and females,
      with recurrence rate, severity of the lesions, and duration for the lesions to
      resolve being greater in the female baboons. Lesions involving the mouth, tongue,
      and lips were most commonly observed in the juvenile population. The lesions
      tended to start as small multiple papules or vesicles, which advanced to large
      pustular or ulcerative areas. Using an every-other-day treatment regimen
      consisting of Nolvasan cleaning and procaine penicillin G injections, it took an
      average of 14 to 21 days for the lesions to resolve totally. Thirty-seven percent
      of the baboons with herpetic lesions experienced another episode of SA8
      infection, usually within 1 year of development of the primary lesion. Several
      complications have been documented to be associated with SA8 infections. Partial
      or total vaginal obstruction is most common, leading to impaired breeding
      performance and pyelonephritis. A vaginal corrective surgical procedure has been
      developed to allow these females to return to productive breeding status within
      the colony. Penile urethral obstruction, also causing pyelonephritis, was
      observed in the male baboons. A case of sciatic neuritis was reported in a baboon
      that presented with self mutilation of the foot; viral isolation revealed the
      etiologic agent to be SA8. Four female baboons with chronic SA8 infections went
      on to develop perineal neoplasms. This is an economically important disease
      entity in captive baboons because it causes severe morbidity, decreased
      reproductive performance, and ultimately death in 1% of the baboon colony each
      year. The baboon is a promising animal model in which to study genital herpes as
      it relates to disease in human beings.

PMID- 9517885
TI  - Shedding and transmission of baboon Herpesvirus papio 2 (HVP2) in a breeding
      colony.
AB  - Baboons in a captive breeding colony were monitored twice a year, and new
      additions were screened on arrival for shedding of Herpesvirus papio 2 (HVP2) and
      serologic reactivity to the agent. For 128 individual animals tested over a
      period of 1.5 years, shedding of infective virus was detected in 13 of 342 swab
      specimens (3.8%), each of these incidents representing shedding by a different
      animal. Among long-term colony animals, infective virus was recovered on only two
      occasions (5 of 236 swab specimens from five individuals). In all but one
      instance, animals shedding virus were infants, not adults, and all animals were
      shedding virus in the oral cavity. One of these five instances was an isolated
      case, but four (three infants and one adult) were clustered within a single
      breeding group. Molecular analyses of the HVP2 isolates from this cluster
      indicated that they likely arose from a single common source, probably the mother
      of one of the infants. None of 31 wild-caught baboons added to the colony during
      this period were found to be shedding infective virus, despite 93.5% of them
      being seropositive for HVP2. In contrast, 6 of 18 adult baboons (all
      seropositive) transferred into the colony from another breeding colony were found
      to be shedding HVP2 either orally (3 of 6) or genitally (3 of 6). In addition, 2
      of 8 juvenile baboons in this shipment were found to be shedding virus in the
      oropharynx. Overall, 10 of 13 instances of HVP2 isolation were from the
      oropharynx rather than the genital tract, and 6 of 13 baboons shedding virus were
      infants or juveniles rather than adults. These results suggest that, although
      venereal transmission of HVP2 occurs among adult animals, oral infection of
      young, sexually immature baboons is not uncommon.

PMID- 9517886
TI  - Epizootic of group B Streptococcus agalactiae serotype V in DBA/2 mice.
AB  - Beta-hemolytic Streptococcus agalactiae serotype V was identified as the cause of
      an infection in laboratory mice. Principally, the organism induced fatal
      septicemia in DBA/2 breeding-age mice. The syndrome appeared to originate as an
      ascending pyelonephritis, which progressed to septicemia. Microscopic lesions
      were found in the heart, kidneys, spleen, and liver, and less commonly in the
      uterus, thoracic cavity, lymph nodes, and lungs. The epizootic was controlled by
      eradication of the breeding colonies, disinfection of the barrier, and
      autoclaving of all equipment. The new replacement colonies have remained free of
      the organism.

PMID- 9517887
TI  - Neuropathologic findings associated with seizures in FVB mice.
AB  - The FVB mouse is used extensively in transgenic research because of its defined
      inbred background, superior reproductive performance, and prominent pronuclei,
      which facilitate microinjection of genomic material. Seizures associated with a
      known mutation and seizure-susceptible inbred strains are well documented in
      mice; however, to the authors' knowledge, seizures in the FVB strain have not
      been evaluated. Affected nonmanipulated FVB/N (n = 5) and transgenic FVB/N mice
      generated, using eight unrelated transgenic constructs (n = 63), were submitted
      for pathologic examination. Most cases were detected during routine observations
      in animal rooms; however, seizure induction by tail tattooing, fur clipping, and
      fire alarms has been observed. The majority of mice were female (62 of 68), with
      mean age of 5.8 months (range, 2 to 16 months). Observations made during seizure
      presentation in 12 of 68 mice included facial grimace, chewing automatism,
      ptyalism with matting of the fur of the ventral aspect of the neck and/or
      forelimbs, and clonic convulsions that frequently progressed to tonic convulsions
      and death. Four mice were dead at presentation, with matting of the fur of the
      neck and forelimbs. The remainder of the mice had nonspecific signs of disease,
      such as lethargy, moribundity, or matting of the fur. Vendor and in-house animal
      health surveillance reports indicated that mice were seronegative to all murine
      pathogens. Results of gross pathologic examination were unremarkable. Microscopic
      findings were limited to the brain and liver. In all mice, neuronal necrosis was
      present in the cerebral cortex, hippocampus, and thalamus. Concurrent astrocyte
      hypertrophy, as evidenced by an increase in glial fibrillary acidic protein
      staining, was detected. Acute coagulative necrosis of centrilobular hepatocytes
      was present in the liver of some cases (19 of 68). Infective agents were not
      detected in selected brain specimens submitted for electron microscopy or in
      brain and liver specimens evaluated by use of special stains. Cytopathologic
      effect was not observed in 3T3, Vero, and BHK-21 cell lines inoculated with brain
      and liver specimens. The ischemic neuronal necrosis observed in these mice is
      consistent with lesions associated with status epilepticus in humans. The
      hepatocellular changes are interpreted to be agonal and associated with terminal
      hypoxia in seizuring animals. These results provide evidence of a previously
      unrecognized, often lethal epileptic syndrome in FVB mice that may have a major
      impact on transgenic research and other disciplines using this mouse strain.

PMID- 9517888
TI  - Pathogenicity of Mycoplasma volis in mice and rats.
AB  - A new species of Mycoplasma, M. volis, was isolated from the respiratory tract of
      clinically normal field-trapped prairie voles (Microtus ochrogaster) that were to
      be housed in close proximity to other rodents. To determine the pathogenic
      potential of the new mycoplasmal isolate, three groups of rodents (Sprague Dawley
      rats, BALB/c mice, and severe combined immunodeficient [SCID] mice) were
      intranasally inoculated with 2 x 10(8) color-changing units (CCU) of M. volis and
      were observed for 4 to 6 weeks. Experimental animals did not manifest clinical
      signs of disease; however, one experimental SCID mouse was euthanized 5 days
      after inoculation because of a severe circling disorder. Lung lesions in
      experimental SD rats ranged from mild to severe bronchial-associated lymphoid
      tissue (BALT) hyperplasia. Lung lesions in BALB/c and SCID mice ranged from no
      lesions to mild pneumonia. We were able to isolate M. volis from some control
      mice, none of which had lung lesions. All mice were seronegative for Sendai
      virus, mouse hepatitis virus, and M. pulmonis. All immunocompetent experimental
      animals (BALB/c mice and Sprague Dawley rats) were seropositive for M. volis. All
      immunocompetent control animals and SCID mice were seronegative for M. volis. Our
      data suggest that M. volis is capable of causing microscopic lesions and
      seroconversion in rats and mice, and therefore these rodents should not be housed
      in close proximity to voles.

PMID- 9517889
TI  - Rapid diagnosis of simian varicella using the polymerase chain reaction.
AB  - Simian varicella virus (SVV) causes sporadic epizootics of a varicella-like
      disease in nonhuman primates. Rapid diagnosis of simian varicella is critical in
      controlling epizootics. A polymerase chain reaction (PCR)-based diagnostic assay
      for detection of SVV DNA in cell culture and clinical samples from SVV-infected
      monkeys was developed. The assay is rapid, specific, and highly sensitive. The
      SVV DNA is readily detected in skin rash specimens and in peripheral blood
      lymphocytes of infected monkeys during the early stages of clinical varicella. In
      addition to providing an important diagnostic tool, the SVV PCR assay is also
      useful for investigating the epidemiology and pathogenesis of simian varicella.

PMID- 9517890
TI  - Prevalence of enterotropic and polytropic mouse hepatitis virus in enzootically
      infected mouse colonies.
AB  - Mouse hepatitis virus (MHV) causes the most prevalent viral infection in
      contemporary laboratory mouse colonies. According to their primary replication
      site, different strains of MHV segregate into two overlapping biotypes,
      enterotropic and polytropic. These two groups vary greatly in disease pattern,
      pathogenicity, immune response, and duration of infection. Historically, the
      polytropic MHV strains represent the extensively studied prototype strains that
      have minimal enterotropism, whereas enterotropic MHV strains have been less
      characterized. Anecdotal reports suggest that most MHV strains encountered today
      belong to the enterotropic biotype. We have identified 15 isolates of MHV from 19
      independent enzootically infected mouse colonies. Sequencing of a variable region
      of the nucleoprotein (N) gene of each isolate confirmed that all were independent
      genetic variants. The principal tissue tropism of the new isolates was determined
      by experimental inoculation of infant mice and examination of intestine, liver,
      spleen, and brain for lesions. Nine isolates infected only intestine; four
      isolates infected intestine and liver; one isolate infected intestine, liver, and
      brain; and one isolate infected liver. These results confirm that the
      enterotropic MHV biotype is predominant in contemporary laboratory mouse
      colonies. The MHV biotype features need to be taken into consideration when
      dealing with MHV infections.

PMID- 9517891
TI  - Improved guinea pig model of cardiac tachyarrhythmias.
AB  - Guinea pigs are frequently used as models for ventricular tachyarrhythmias,
      including polymorphic ventricular tachycardia (VT) and ventricular fibrillation.
      However, applications of the model for short-term therapies are limited because
      the arrhythmias are transient, typically lasting <5 sec. Thus, spontaneous
      termination cannot be easily distinguished from effective short-term therapy in
      standard models. Results of this study confirmed an improved induction method
      that consistently extends the arrhythmias to 30 sec or longer. In 10 (400- to
      1200-g) male guinea pigs, a pacing electrode was advanced in the esophagus. The
      anode for pacing was a wire advanced through a 20-gauge needle across the
      diaphragm toward the ventricular apex. Two 12-mm-diameter electrodes were placed
      on the skin on opposing aspects of the thorax for T-wave stimulation. The blood
      pressure in the carotid artery was continuously monitored. Two traditional
      methods were used to induce VT: 2 sec of a 50-Hz square wave, and a single 200
      V/5 ms transthoracic stimulus at the peak of the T-wave after pacing at 80% of
      the intrinsic R-R interval. A third novel method also was used: a single 200 V/5
      ms transthoracic stimulus at the peak of the T-wave after a rapid pacing
      sequence. The rapid pacing sequence was a 25-stimulus sequence, which accelerated
      to end with 15 beats at the shortest pacing interval for which all pacing stimuli
      captured. A tachyarrhythmia was defined as any abnormally rapid surface
      electrocardiographic waveform lasting at least 2 sec after termination of the
      initiating stimulus. Between 5 and 23 attempts were made to induce
      tachyarrhythmias in each animal. In four additional animals (>800 g), the
      efficacy of an established short-term therapy for tachyarrhythmias was measured,
      using the proposed rapid pacing model. All arrhythmias induced by use of the
      three induction methods were polymorphic VT accompanied by complete hemodynamic
      collapse. In hearts weighing >2.5 g (body mass >800 g), 100% of arrhythmia
      episodes were sustained for 30 sec or longer when initiated after rapid pacing,
      as opposed to only 55% sustained by use of other induction methods (P < 0.01).
      The efficacy results for the established short-term therapy matched those
      previously reported for 100-kg calves. A brief period of rapid pacing facilitates
      initiation of consistent, sustained ventricular tachyarrhythmias in large guinea
      pigs, eliminating spontaneous termination as a confounding factor in the study of
      short-term therapies.

PMID- 9517892
TI  - Pulmonary eosinophilia and inflammation in allergic mice.

PMID- 9517893
TI  - Animal model of uterine adenomyosis: induction of the lesion in rats by ectopic
      pituitary isografting.
AB  - Adenomyosis is a benign pathologic disorder of the uterine endometrial tissues
      whereby endometrial components, such as glands and stroma, invade the myometrium.
      Transplantation of a single anterior pituitary gland into the uterine lumen
      induced adenomyosis in six of eight Wistar rats 12 months after the grafting.
      Adenomyotic changes were not observed in six sham-operated control rats. Electron
      microscopic observations indicated that cells of the inner layer of the
      myometrium were reduced in size and irregularly shaped in the areas bearing
      adenomyotic changes. In pituitary-grafted rats, healthy corpora lutea remained in
      the ovaries, whereas control rats had degenerating ovaries. These findings are
      consistent with the results of pituitary-grafted mice reported previously and
      support our assertion that a hormonal milieu induced by pituitary grafting is
      favorable for development of uterine adenomyosis.

PMID- 9517894
TI  - Relationship between inspiratory pressure and tidal volume in the anesthetized
      canine.
AB  - Hounds undergoing prolonged or complicated surgical procedures are often
      underventilated, as indicated by blood gas and end-tidal CO2 (CO2) values when
      using published ventilatory guidelines. We investigated the relationship between
      body weight, tidal volume, and inspiratory pressure delivered by the ventilator
      (lung inflation pressure) in 59 anesthetized hounds (19 to 33 kg). Animals were
      ventilated under positive pressure control and noninvasively instrumented to
      monitor blood pressure, ECG, oxygen saturation, CO2, and tidal volume. Weight,
      sex, and thorax measurements were recorded. All dogs were monitored at lung
      inflation pressures of 10, 14, and 18 cm H2O, with measurements recorded once CO2
      stabilized. Veterinary guidelines recommend tidal volumes of 10 to 15 ml/kg of
      body weight and lung inflation pressures of 15 to 25 cm H2O. When inflation
      pressure was below guidelines (10), tidal volume was "normal" (10 to 15 ml/kg),
      but the animals were underventilated. When inflation pressure was "normal" (14 or
      18 cm H2O), tidal volume was above guidelines. Physiologic variables were normal
      only when inflation pressure was 14 cm H2O. Weight and thorax depth accounted for
      32 and 6%, respectively, of tidal volume variability, and tidal volume varied by
      +/- 250 ml at any given body weight and inflation pressure. None of the measured
      physical variables accurately predicted tidal volume. These data suggest that the
      inconsistency in tidal volume is due to a previously undescribed variability in
      respiratory compliance in the anesthetized hound and that the guidelines for
      ventilation during surgery need further investigation.

PMID- 9517896
TI  - Effects of feeding a liquid diet for one year to New Zealand White rabbits.
AB  - We compared the long-term effects of a newly designed liquid diet with a
      commercially available dry diet in New Zealand White rabbits. Body weight gain,
      feed consumption, and plasma lipid concentrations were measured periodically
      throughout the 1-year study. In addition, specific hepatic enzyme activities in
      serum were quantified to examine the effects of liquid diet on the liver over the
      1-year feeding trial. At 52 weeks, body weight gains between the liquid- and dry
      fed groups were similar. Regardless of sex, plasma phospholipid concentrations
      were higher in the control group than in the liquid-fed group. Plasma
      triglyceride concentrations were increased in liquid-fed female rabbits, compared
      with either male group or control-fed females. A somewhat similar effect was
      observed in plasma cholesterol concentration, which was higher in female rabbits
      regardless of diet type. After the 52-week trial, the rabbits had no clinical
      biochemical signs of liver damage. Results of this study indicate that a liquid
      diet can be fed to New Zealand White rabbits for a long period, and may provide
      an alternative route (food source) for future pathophysiologic studies.

PMID- 9517895
TI  - Effect of in vivo administration of all trans-retinoic acid on the hemopoietic
      cell populations of the spleen and bone marrow: profound strain differences
      between A/J and C57BL/6J mice.
AB  - All trans-retinoic acid (ATRA) is currently the subject of much interest as a
      possible anti-tumor therapeutic agent, especially for leukemias. One postulated
      mechanism for its ameliorative action on tumor growth is via stimulating cells of
      the immune system and its accessory cells. Mice of the A/J strain have an
      unusually high frequency of leukemia, whereas C57BL/6J mice rarely develop
      leukemia, and moreover, unlike A/J mice, have strong resistance to a variety of
      pathogens. The purpose of the study reported here was twofold: to investigate
      whether A/J mice have quantitative deficiencies in their specific and nonspecific
      disease defense mechanisms (lymphoid, granuloid, and monocytoid cells) relative
      to those of C57BL/6J mice, and if so, whether in vivo administration of an ATRA
      could quantitatively augment these cells in the major organs housing them: the
      spleen and the bone marrow. Furthermore, for the lymphoid and granuloid lineages,
      absolute numbers of precursors and of differentiated (mature) cells also were
      enumerated. The results indicate that A/J mice have significantly lower numbers
      of lymphoid, granuloid, and monocytoid--but not erythroid--cells in the spleen
      and/or bone marrow than do C57BL/6J mice. Also, sensitivity to ATRA was generally
      more profound in A/J mice than in C57BL/6 mice with respect to several
      hemopoietic cell lineages. These observations collectively suggest a need for
      considerable prudence in selection of inbred strains of mice, not only because of
      the possibility of wide interstrain variations in hemopoietic and immune cell
      mediated functions, but also because of potential differences in the responses of
      various strains of common laboratory mice to pharmacologic agents.

PMID- 9517898
TI  - Diagnostic exercise: vascular endothelial lesions in athymic nu/nu mice.

PMID- 9517897
TI  - Comparison of four diagnostic methods for detection of Helicobacter species in
      laboratory mice.
AB  - Four species of Helicobacter--H. muridarum, "H. rappini," H. hepaticus, and H.
      bilis--have been identified in the gastrointestinal tract of rodents. The
      association of Helicobacter species with chronic gastrointestinal diseases in
      mice has raised concern about their impact on research results. In this study,
      different methods for detection of Helicobacter species in the mouse intestinal
      tract were compared: polymerase chain reaction (PCR) amplification of 16S rRNA
      gene sequences, bacterial culture, electron microscopy, and histologic
      examination (Steiner stain). The PCR method was more sensitive in detecting
      murine Helicobacter species than was culture, electron microscopy, or histologic
      examination. Of the cecal specimens identified as Helicobacter species-positive
      by PCR, approximately 60% were identified as positive by each of the other
      methods. An 87.5% concordance was obtained by PCR screening of DNA from fecal and
      cecal specimens. Differentiation among murine Helicobacter species by colony
      morphologic or histologic features was not possible. Scanning electron microscopy
      and histologic examination indicated greater numbers of helical microorganisms,
      specifically H. hepaticus, in the cecum than in the colon. These results indicate
      that the PCR assays used can be performed on feces as a noninvasive means for
      rapidly screening large numbers of colony mice for murine Helicobacter species.

PMID- 9517899
TI  - Progressive necrosing dermatitis of the pinna in outbred mice: an institutional
      survey.

PMID- 9517900
TI  - Detection and typing of lactate dehydrogenase-elevating virus RNA from
      transplantable tumors, mouse liver tissues, and cell lines, using polymerase
      chain reaction.

PMID- 9517901
TI  - New method for genotyping the mouse Lep(ob) mutation, using a polymerase chain
      reaction assay.

PMID- 9517902
TI  - The long-term course of autistic disorders: update on follow-up studies.
AB  - The majority of children with autism show deviance and socially or
      psychiatrically handicapping conditions throughout life. Only a small proportion
      of those with classical childhood autism lead independent adult lives. Others,
      particularly those with 'high-functioning' autism and so-called Asperger syndrome
      will improve enough to live an independent adult life. The level of mental
      retardation and other comorbid conditions (such as medical syndromes and other
      neuropsychiatric disorders, including epilepsy) is important in predicting
      outcome. An IQ below 50 around school age predicts severe restriction of social
      and adaptive functioning in adult life. The absence of communicative speech at 5
      6 years of age is indicative of a poorer long-term overall outcome. There is a
      clear co-variation between IQ and level of communication, but probably there is
      some prognostic factor in language development apart from this. Measures of
      flexibility and cognitive shifting abilities tend to be good predictors of social
      outcome in a few studies. There is a continued need for prospective, longitudinal
      studies of children with autism spectrum disorders, particularly in Asperger
      syndrome. The role of interventions of various kinds needs to be addressed in
      such studies.

PMID- 9517903
TI  - Non-verbal behaviour deficits in schizophrenia: an ethological study of drug-free
      patients.
AB  - The aims of this study were (i) to define the dimensions of non-verbal behaviour
      which distinguish between schizophrenic patients and control subjects and (ii) to
      examine the relationship between patients' non-verbal behaviour and clinical
      symptoms. The non-verbal behaviour of 28 drug-free patients with schizophrenia
      according to Research Diagnostic Criteria (RDC) and 25 control subjects was
      videotaped during interviews and scored according to an ethological scoring
      system. Patients' symptoms were rated on the Scale for the Assessment of Negative
      Symptoms, the Scale for the Assessment of Positive Symptoms and the Brief
      Psychiatric Rating Scale. As a group, schizophrenic patients showed a global
      restriction of non-verbal expressiveness, as indicated by their lower scores on
      prosocial behaviour, gesture and conflict. However, some patients had normal
      ethological profiles. Non-verbal behaviour was largely independent of negative
      and positive symptoms. Deficits in non-verbal behaviour may play a role in
      determining or aggravating dysfunctional patterns of relating in schizophrenia.
      Ethological analysis provides further support for the model that conceptualizes
      positive symptoms, negative symptoms and disorders of social relationships as
      three separate dimensions of the schizophrenic syndrome.

PMID- 9517904
TI  - Social adjustment in schizophrenia: factors predictive of short-term social
      adjustment in a sample of schizophrenic patients.
AB  - A sample of 60 Spanish schizophrenic patients was studied in order to ascertain
      the relationship between their relatives' expressed emotion (EE) and social
      adjustment after 2 years of follow-up. The average extent of the disability did
      not increase over time, and differences in dysfunction rates between the various
      specific social roles were identified. No differences in social outcome were
      detected between patients with high EE and low EE families. Three factors which
      predict social adjustment outcome were obtained using logistic regression
      analysis, namely clinical conditions, baseline social adjustment and the
      occurrence of a psychotic relapse during the follow-up period.

PMID- 9517905
TI  - Age at onset of delusional disorder is dependent on the delusional theme.
AB  - The main aim of this study was to investigate whether or not subtypes of
      delusional disorder diagnosed by DSM-III-R show differences in age at onset and
      sex distribution. All out-patients first seen at the psychiatry clinic between
      1989 and 1994 were diagnosed by DSM-III-R. Of 4144 out-patients, 51 patients
      (1.2%) were selected as having delusional disorder, and the demographic data and
      clinical profiles for these subjects were evaluated prospectively by the
      psychiatrists. Females outnumbered males by a ratio of 3:1. The type of
      delusional disorder most frequently encountered was the persecutory type,
      followed by the somatic type, jealous type and unspecified type. The age at onset
      differed significantly according to the type of delusional disorder, the oldest
      age at onset being associated with the persecutory type, and the youngest with
      the somatic type.

PMID- 9517906
TI  - Onset of acute psychotic states in India: a study of sociodemographic, seasonal
      and biological factors.
AB  - This is a comparative study of patients with acute-onset, non-affective, non
      organic, remitting psychoses and with non-remitting or schizophrenic psychoses in
      India. Two groups of patients with acute remitting and non-remitting or
      schizophrenic psychoses were compared with regard to the following variables:
      month of onset of psychosis; presence of stress, particularly fever, within 4
      weeks preceding the onset of psychosis; childbirth within 12 weeks preceding the
      onset of psychosis; gender differences. It was found that the acute remitting
      psychoses showed an overrepresentation of females, a higher frequency of
      associated stress preceding the onset of psychosis, more often had onset during
      the summer months, i.e. between May and September, and had fever and childbirth
      preceding the onset of psychosis in a significantly higher proportion of
      patients, compared to acute non-remitting psychoses or schizophrenia. The
      implications of the findings which point towards biological factors in the
      aetiology of acute remitting psychoses are discussed.

PMID- 9517907
TI  - Early neuropsychological impairment in HIV-seropositive intravenous drug users:
      evidence from the Italian Multicentre Neuropsychological HIV Study.
AB  - The aim of the Italian Multicentre Neuropsychological HIV Study is to assess the
      prevalence and natural history of cognitive deficit in intravenous drug users
      (i.v.DUs) during the asymptomatic phase of HIV infection. The study is currently
      being conducted in four centres (Napoli, Benevento, Verona and Pavia) whose
      catchment areas are characterized by different levels of prevalence of HIV
      infection. Cognitive evaluation is being performed by means of a standardized
      neuropsychological test battery. A total of 251 subjects (167 males and 84
      females) have been recruited in the cross-sectional phase of the study, including
      75 asymptomatic HIV-seropositive i.v.DUs (HIV+/i.v.DUs), 97 HIV-seronegative
      i.v.DUs (HIV-/i.v.DUs) and 79 non-i.v.DU seronegative controls matched to i.v.DUs
      with regard to sex, age and educational level. The prevalence of global cognitive
      impairment (performance at least 1.5 standard deviations worse than the average
      of the control group, on at least two out of five tests) was significantly higher
      in HIV+/i.v.DUs than in either HIV-/i.v.DUs (22.7% vs. 8.2%; P < 0.01) or healthy
      controls (22.7% vs. 2.5%; P < 0.001). The difference between HIV-/i.v.DUs and
      healthy controls was not statistically significant (8.2% vs. 2.5%; P = 0.19). The
      results of this study lend further support to the 'cerebral reserve' model. The
      cerebral reserve could indeed be reduced in i.v.DUs as a consequence of chronic
      exposure to the substance of abuse, so that these subjects become more vulnerable
      to direct and indirect neurotoxic effects of HIV.

PMID- 9517908
TI  - Mitral valve prolapse and autonomic function in panic disorder.
AB  - We investigated the significance of mitral valve prolapse (MVP) and autonomic
      function in 121 patients diagnosed with panic disorder (PD). The incidence of MVP
      was higher in these patients (32.2%) than in the healthy controls (16.7%), but
      the difference was not significant. In the group with PD accompanied by
      depression, the MVP rate was 58.1%, significantly higher than the value of 25.7%
      observed in the PD patients without depression. The severity of MVP was mild;
      nearly all of the cases were silent, without cardiac murmur, and there was no
      problem with the left ventricular function. The coefficient of variation for R-R
      intervals on electrocardiograms (CV R-R) was smaller in patients with PD than in
      healthy controls. The CV R-R of PD patients was significantly lower in the group
      with MVP than in the group without MVP, suggesting a strong association with the
      parasympathetic nervous system. Since the CV R-R tended to decrease in the
      presence of depression, involvement of the parasympathetic nervous system was
      inferred.

PMID- 9517909
TI  - Suicidality and aggressive behaviour.
AB  - Psychiatrists have always maintained that there is a relationship between
      aggressive behaviour and suicide in depressed patients. However, this
      relationship is based on inconsistent and undocumented hypotheses, not on
      reliable clinical experimental data. The present study was designed to
      investigate the relationship between aggressive behaviour assessed by means of
      the Buss and Durkee Hostility Inventory (BDHI), and suicide in a sample of 134
      depressed out-patients. The group with a higher level of suicidal behaviour was
      of younger age. The association between depressive subtypes (major depression,
      recurrent; major depression, single episode; bipolar disorder, depressive
      episode; dysthymia) and suicidality was found to be statistically significant. In
      contrast, there was no correlation between depressive subtypes and aggressive
      behaviour. The relationship between suicide and guilt as measured by the BDHI
      suggests that, in depression, suicidal behaviour becomes part of a symptom
      pattern in which aggression does not appear to be the main component. The suicide
      dimension arises when the cognitive sphere is involved. In fact, in depression,
      suicide is included among the cognitive disturbances, together with guilt,
      paranoid and obsessive-compulsive symptoms, depersonalization/derealization and
      agitation.

PMID- 9517910
TI  - Interaction of affective and cognitive impairments in the suicidal state: a brief
      elaboration.
AB  - This report examines the comorbidity among three key symptoms associated with
      suicidal intent, namely hopelessness, depression and unusual thinking. A total of
      97 out-patients with suicidal thoughts were assessed using the Beck Hopelessness
      Scale, the anxious depression and unusual thinking factor scales of the Derogatis
      Symptom Checklist-90, and the Beck Scale for Suicide Ideation. It was found that,
      in considering the interaction between key presenting symptoms, the combination
      of hopelessness and unusual thinking (which consisted of symptoms such as
      'trouble concentrating' and 'mind going blank') was the strongest predictor of
      the seriousness of current suicidal inclinations.

PMID- 9517911
TI  - A cross-sectional audit of benzodiazepine use among general practice patients.
AB  - In order to assess how many general practice patients take benzodiazepines for
      long periods, a cross-sectional audit of clinical practice was conducted. During
      a 3-day census period, 26 general practitioners in the area of Bergamo, Italy,
      entered into the study every patient who was taking benzodiazepines. The
      prevalence of use of this class of drugs was 14.0% (CI 12.5-15.7), while the
      prevalence of daily use for 12 months or more was 4.7% (CI 3.8-5.8). Finally, the
      prevalence of very long-term use of benzodiazepines, i.e. those taking these
      drugs for more than 10 years, was 0.65% (CI 0.34-1.14). Compared to non-long-term
      users, long-term users were older (OR 2.38, CI 1.39-4.08) and had a lower level
      of education (OR 2.40, CI 1.04-5.54). In addition, insomnia was associated with
      long-term use of this class of drugs (OR 1.82, CI 1.02-3.24). These findings
      provide evidence that the long-term use of benzodiazepines is an important issue
      in everyday general practice and that this calls for precise management tactics.

PMID- 9517912
TI  - Double-blind study of the efficacy and safety of milnacipran and imipramine in
      elderly patients with major depressive episode.
AB  - The novel antidepressant agent milnacipran is a dual and equipotent serotonin and
      noradrenaline reuptake inhibitor. The aim of this double-blind study was to
      compare the efficacy and safety of milnacipran (50 mg twice daily) with that of
      imipramine (50 mg twice daily) in elderly patients with major depressive episode.
      A total of 219 patients were randomly assigned to 8 weeks of double-blind
      treatment with either milnacipran or imipramine; 72 patients withdrew from the
      study. At the end of treatment no significant differences were found between
      milnacipran and imipramine in antidepressant efficacy. A significantly greater
      number of side-effects, particularly anticholinergic effects, was observed in the
      imipramine group. Milnacipran may be preferable to imipramine in elderly
      depressed patients, as it provides the same antidepressant activity as imipramine
      with a lower incidence of side-effects, and does not impair cognitive ability.

PMID- 9517914
TI  - Case report: akathisia abolished by passive movement.
AB  - Akathisia is a common and poorly understood complication of treatment with
      psychotropic medication. A patient is described whose severe akathisia was
      abolished by passive motion when travelling as a car passenger. The case reported
      here highlights the importance of sensory input in akathisia.

PMID- 9517913
TI  - Time to initial medical presentation in a first-admission group with depression.
AB  - This paper examines the interval between the onset of depressive illness and
      subsequent medical presentation in a group of patients undergoing their first
      psychiatric admission with moderate to severe depression. The average
      preconsultation interval was 76 days, compared with an average time from
      consultation to the commencement of adequate treatment of 40 days. The time to
      initial consultation was found to correlate significantly with neuroticism, but
      not with sociodemographic factors. This study suggests that neuroticism may act
      as a predictor of poor outcome in depressive illness through its impact on help
      seeking behaviour.

PMID- 9517915
TI  - Structural organization of cornified cell envelopes and alterations in inherited
      skin disorders.
AB  - The cornified cell envelope is a highly insoluble and extremely tough structure
      formed beneath the cell membrane during terminal differentiation of
      keratinocytes. Its main function is to provide human skin with a protective
      barrier against the environment. Sequential cross-linking of several integral
      components catalyzed by transglutaminases leads to a gradual increase in the
      thickness of the envelope and underscores its rigidity. Key structural players in
      this cross-linking process include involucrin, loricrin, SPRRs, elafin, cystatin
      A, S100 family proteins, and some desmosomal proteins. The recent identification
      of genetic skin diseases with mutations in the genes encoding some of these
      proteins, including transglutaminase 1 and loricrin, has disclosed that abnormal
      cornified cell envelope synthesis is significantly involved in the
      pathophysiology of certain inherited keratodermas and reflects perturbations in
      the complex, yet highly orderly process of cornified cell envelope formation in
      normal skin biology.

PMID- 9517916
TI  - Not all chronic urticaria is "idiopathic"!
AB  - The aetiology of chronic urticaria in the majority of patients is elusive. The
      cause of physical urticarias (dermographism, delayed pressure urticaria, cold
      urticaria) is unknown. We have identified a subset of chronic "idiopathic"
      urticaria patients, representing approximately 30% of the total in which the
      disease is caused by the presence of IgG autoantibodies against the high affinity
      IgE receptor (FcepsilonRIalpha). This functional autoantibody stimulates normal
      (albeit vicarious) activation of mast cells and basophils via FcepsilonRI,
      causing whealing and angioedema. Anti-FcepsilonRI-positive patients are
      recognized by a combination of autologous serum skin testing and evoked histamine
      release from basophils of normal human donors. Autoantibody-positive and 
      negative patients are clinically indistinguishable and are treated routinely by
      combinations of H1 and occasionally H2-antihistamines in both cases. However,
      severely affected patients who are anti-FcepsilonRI-positive can also be treated
      by non-specific immunotherapy (plasma pheresis, intravenous immunoglobulin,
      cyclosporin.

PMID- 9517917
TI  - Increased activity of cathepsin B in fibroblasts isolated from primary melanoma
      in comparison to fibroblasts from normal skin.
AB  - We determined activity of cathepsin B in early-passage fibroblasts isolated from
      primary melanoma and in fibroblasts from normal skin. Our results show an up to 5
      fold increase in activity of cathepsin B in the tumor-derived fibroblasts in
      comparison to the fibroblasts from normal skin. We conclude that fibroblasts
      isolated from melanoma tissue are altered with regard to their specific activity
      of cathepsin B and preserve this elevated activity in early-passage cell culture.
      The data support the idea that stromal cells are not passive elements of the
      peritumoral environment but actively participate in the production of proteolytic
      enzymes.

PMID- 9517918
TI  - Skin2--an in vitro human skin model: the correlation between in vivo and in vitro
      testing of surfactants.
AB  - The availability of an in vitro test system to replace animal testing of
      potential irritants is becoming more and more urgent especially in Europe as a
      consequence of the European Community Cosmetics Directive. To evaluate the
      ability of Advanced Tissue Sciences' (ATS) ZK1301 skin model to predict the skin
      irritation potential of surfactants, we performed a pilot validation study
      utilizing four different laboratories. The in vitro protocol was designed as a
      quantitative pre-screen for the clinical patch studies. Sixteen substances,
      representing various surfactant categories and ranges of irritation potential,
      were tested. The 3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide
      (MTT) assay was used to quantitate viability in vitro. We documented the
      viability of tissues exposed to unknown substances for specific periods. The in
      vitro results were calculated as percent distilled water controls (DWC). The time
      required to reduce the viability of each tissue to 50% of the distilled water
      controls (T50) was compared to mean erythema and edema scores from the clinical
      studies by Pearson's correlation. The individual laboratories demonstrated
      coefficients of 0.72. The results indicated that the 30 min percent untreated
      control values best predicted the 24 h clinical patch scores. No statistically
      significant interlab variability was found. Only one false negative was seen when
      non/mild and moderate/severe irritant categories were assigned according to the
      in vitro scores. These results demonstrate that the skin2 in vitro test system
      may serve as a good screening method prior to clinical patch studies.

PMID- 9517919
TI  - In vitro metabolism by human skin and fibroblasts of retinol, retinal and
      retinoic acid.
AB  - The metabolism of radio-labelled retinol, retinal and retinoic acid by fresh
      human skin as well as by human dermal fibroblasts have been investigated in
      vitro. Surgically removed human skin biopsies were placed at the air liquid
      interface, and treated topically for 24 h with retinoids. At the end of the
      treatment period, epidermis and dermis were separated by heat. Epidermis, dermis
      and medium were subsequently extracted and resulting fractions were analysed by
      HPLC. Dermal fibroblast cultures were treated and analysed in a comparable
      manner. Topical application of retinoids resulted in gradient concentrations
      within the skin. For each fraction, metabolites and unchanged product proportions
      were determined by HPLC. After treatment with retinol and retinal, low but
      significant amounts of retinoic acid were detected in the epidermis, as well as
      in the dermis (30 pmol to 90 pmol). In comparison, treatments with retinoic acid
      itself, led to higher level of retinoic acid in the epidermis and in the dermis
      (respectively 2050 and 420 pmol). Cultured human dermal fibroblasts, treated with
      retinol and retinal, formed retinoic acid as well as several other metabolites
      (retinol esters, reduction of retinal to retinol...). Taken together, our results
      are consistent with an action of retinol or retinal on the skin via a retinoic
      acid formation and a metabolic function of the dermis.

PMID- 9517920
TI  - TNF-alpha, RANTES, and MCP-1 are major chemoattractants of murine Langerhans
      cells to the regional lymph nodes.
AB  - We have previously reported that lymph node cells generated chemotactic factors
      for Langerhans cells (LCs) in the induction phase of contact dermatitis. In order
      to clarify the chemotactic factors involved in migration to the regional lymph
      nodes, we investigated the migratory activity of murine LCs toward several
      cytokines and chemokines in vitro. One-day cultured LC-enriched epidermal cells
      were added to the upper compartment of a modified Boyden chamber and cytokines
      were added to the lower compartment. We counted dendritic cells migrated to the
      lower chamber as LCs under phase contrast microscopy. About 99% of migrated
      dendritic cells were positively reacted with anti-Ia(d) and NLDC145 antibodies
      and considered to be LCs. We could detect LC migration more accurately by this
      direct examination than by counting the migrated cells in the filter membrane of
      a Boyden chamber. In our system, migration of murine epidermal LCs was stimulated
      by TNF-alpha, RANTES and MCP-1, but not by GM-CSF, IL-1beta, IL-4, and IL-6. TNF
      alpha induced LC migration at concentrations from 4 x 10(3) U/ml to 5 x 10(4)
      U/ml. RANTES at concentrations from 10 to 100 ng/ml and MCP-1 at a concentration
      of 100 ng/ml induced LC migration in a dose-dependent manner. These data
      confirmed that TNF-alpha, RANTES, and MCP-1 induced LC migration from epidermis
      during contact sensitization.

PMID- 9517921
TI  - Inhibition of acute-, latent-, and chronic-phase human immunodeficiency virus
      type 1 (HIV-1) replication by a bistriazoloacridone analog that selectively
      inhibits HIV-1 transcription.
AB  - Nanomolar concentrations of temacrazine (1,4-bis[3-(6-oxo-6H-v-triazolo[4,5,1
      de]acridin-5-yl)amino-propyl ]piperazine) were discovered to inhibit acute human
      immunodeficiency virus type 1 (HIV-1) infections and suppress the production of
      virus from chronically and latently infected cells containing integrated proviral
      DNA. This bistriazoloacridone derivative exerted its mechanism of antiviral
      action through selective inhibition of HIV-1 transcription during the
      postintegrative phase of virus replication. Mechanistic studies revealed that
      temacrazine blocked HIV-1 RNA formation without interference with the
      transcription of cellular genes or with events associated with the HIV-1 Tat and
      Rev regulatory proteins. Although temacrazine inhibited the in vitro 3'
      processing and strand transfer activities of HIV-1 integrase, with a 50%
      inhibitory concentration of approximately 50 nM, no evidence of an inhibitory
      effect on the intracellular integration of proviral DNA into the cellular genome
      during the early phase of infection could be detected. Furthermore, temacrazine
      did not interfere with virus attachment or fusion to host cells or the enzymatic
      activities of HIV-1 reverse transcriptase or protease, and the compound was not
      directly virucidal. Demonstration of in vivo anti-HIV-1 activity by temacrazine
      identifies bistriazoloacridones as a new class of pharmaceuticals that
      selectively blocks HIV-1 transcription.

PMID- 9517922
TI  - In vitro activities of cefminox against anaerobic bacteria compared with those of
      nine other compounds.
AB  - The agar dilution MIC method was used to test the activity of cefminox, a beta
      lactamase-stable cephamycin, compared with those of cefoxitin, cefotetan,
      moxalactam, ceftizoxime, cefotiam, cefamandole, cefoperazone, clindamycin, and
      metronidazole against 357 anaerobes. Overall, cefminox was the most active beta
      lactam, with an MIC at which 50% of isolates are inhibited (MIC50) of 1.0
      microg/ml and an MIC90 of 16.0 microg/ml. Other beta-lactams were less active,
      with respective MIC50s and MIC90s of 2.0 and 64.0 microg/ml for cefoxitin, 2.0
      and 128.0 microg/ml for cefotetan, 2.0 and 64.0 microg/ml for moxalactam, 4.0 and
      > 128.0 microg/ml for ceftizoxime, 16.0 and > 128.0 microg/ml for cefotiam, 8.0
      and >128.0 microg/ml for cefamandole, and 4.0 and 128.0 microg/ml for
      cefoperazone. The clindamycin MIC50 and MIC90 were 0.5 and 8.0 microg/ml,
      respectively, and the metronidazole MIC50 and MIC90 were 1.0 and 4.0 microg/ml,
      respectively. Cefminox was especially active against Bacteroides fragilis (MIC90,
      2.0 microg/ml), Bacteroides thetaiotaomicron (MIC90, 4.0 microg/ml), fusobacteria
      (MIC90, 1.0 microg/ml), peptostreptococci (MIC90, 2.0 microg/ml), and clostridia,
      including Clostridium difficile (MIC90, 2.0 microg/ml). Time-kill studies
      performed with six representative anaerobic species revealed that at the MIC all
      compounds except ceftizoxime were bactericidal (99.9% killing) against all
      strains after 48 h. At 24 h, only cefminox and cefoxitin at 4x the MIC and
      cefoperazone at 8x the MIC were bactericidal against all strains. After 12 h, at
      the MIC all compounds except moxalactam, ceftizoxime, cefotiam, cefamandole,
      clindamycin, and metronidazole gave 90% killing of all strains. After 3 h,
      cefminox at 2 x the MIC produced the most rapid effect, with 90% killing of all
      strains.

PMID- 9517923
TI  - Diversity of VanA glycopeptide resistance elements in enterococci from humans and
      nonhuman sources.
AB  - Elements mediating VanA glycopeptide resistance in 106 diverse enterococci from
      humans and nonhuman sources were compared with the prototype VanA transposon,
      Tn1546, in Enterococcus faecium BM4147. The isolates included 64 from individual
      patients at 15 hospitals in the United Kingdom (isolated between 1987 and 1996)
      and 42 from nonhuman sources in the United Kingdom (27 from raw meat, 7 from
      animal feces, and 8 from sewage). VanA elements were assigned to 24 groups
      (designated groups A to X) with primers that amplified 10 overlapping fragments
      of Tn1546. Ten groups of elements were found only in human enterococci, eight
      groups of elements were unique to nonhuman strains, and six groups of elements
      were common in enterococci from all sources. Elements indistinguishable from
      Tn1546 (group A) were observed more frequently in enterococci from nonhuman
      sources (34 versus 9%) but were identified in enterococci that caused outbreaks
      in hospital patients between 1987 and 1995. The most common group found in human
      enterococci (group H; 33%) was rarely observed in enterococci from other sources
      (5%). Group H elements differed from Tn1546 in three regions and included a novel
      insertion sequence, designated IS1542, between orf2 and vanR. The VanA elements
      of 14 other groups had a similar insertion at this position and/or distinct
      insertions at other positions. We conclude that VanA elements in enterococci are
      heterogeneous, although all show regions of homology with Tn1546. Furthermore,
      the elements most common among the human and nonhuman enterococci studied were
      different. This approach may be useful for monitoring the evolution of VanA
      resistance and may also be applicable in local "snapshot" epidemiological
      studies. However, as transposition events involving insertion sequences accounted
      for the differences observed between several groups, the stability of the
      elements must be assessed before their true epidemiological significance can be
      determined.

PMID- 9517924
TI  - Inhibition of RNA synthesis as a therapeutic strategy against Aspergillus and
      Fusarium: demonstration of in vitro synergy between rifabutin and amphotericin B.
AB  - We investigated the in vitro antifungal activity of amphotericin B, alone and in
      combination with rifabutin, an inhibitor of bacterial RNA polymerase, against 26
      clinical isolates of Aspergillus and 25 clinical isolates of Fusarium. Synergy or
      additivism between these drugs was demonstrated against all isolates tested.
      Amphotericin B MICs were reduced upon combination with rifabutin from a mean of
      0.65 microg/ml to a mean of 0.16 microg/ml against Aspergillus, and from a mean
      of 0.97 microg/ml to a mean of 0.39 microLg/ml against Fusarium (P < 0.000001 for
      both). Similarly, the MICs of rifabutin were reduced upon combination with
      amphotericin B from a mean of >32 microg/ml to a mean of 1.1 microg/ml against
      both fungi (P < 0.000001 for both). These positive interactions were corroborated
      by a colony count study with two Fusarium isolates, for which treatment with the
      combination of subinhibitory concentrations of amphotericin B (at concentrations
      2- and 4-fold less than the MIC) and rifabutin (at concentrations ranging from 4-
      to 64-fold less than the MIC) resulted in 3.2-log reductions in colony counts
      compared to those after treatment with either drug alone. Inhibition of RNA
      synthesis was shown to be the mechanism of antifungal activity. These results
      suggest that inhibition of fungal RNA synthesis might be a potential target for
      antifungal therapy.

PMID- 9517927
TI  - Amphotericin B colloidal dispersion combined with flucytosine with or without
      fluconazole for treatment of murine cryptococcal meningitis.
AB  - Studies with animals and in vitro studies have demonstrated that flucytosine plus
      amphotericin B or fluconazole has significantly improved mycologic activity
      against meningitis caused by Cryptococcus neoformans compared to the activity of
      amphotericin B or fluconazole used alone. However, few doses have been tested in
      combination. This study evaluated the antifungal efficacy of amphotericin B
      colloidal dispersion (ABCD) combined with flucytosine with and without
      fluconazole in a murine model of cryptococcal meningitis. The following dosages
      were tested: ABCD at 0 to 12.5 mg/kg of body weight given intravenously 3
      days/week, flucytosine at 0 to 110 mg/kg/day, and fluconazole at 0 to 50
      mg/kg/day. Meningitis was established in male BALB/c mice by intracerebral
      injection of C. neoformans. Treatment with flucytosine with or without
      fluconazole dissolved in the sole source of drinking water was started on day 2;
      animals were sacrificed at 16 days, and the numbers of fungal colonies in the
      brain were quantified. A survival rate of 100% was achieved with ABCD plus
      flucytosine without fluconazole; however, the addition of fluconazole was
      required to prevent weight loss (P < 0.00001) and to achieve the maximum
      antifungal effect (P < 0.00001). The only region of dose combinations for which
      the 99% confidence intervals were less than 100 CFU/g of brain was defined by
      ABCD at 5.0 to 7.5 mg/kg combined with flucytosine at 20 to 60 mg/kg/day and
      fluconazole at 30 to 40 mg/kg/day. The triple combination of ABCD plus
      flucytosine and fluconazole was necessary to achieve the greatest antifungal
      activity.

PMID- 9517926
TI  - Pharmacodynamic evaluation of factors associated with the development of
      bacterial resistance in acutely ill patients during therapy.
AB  - The selection of bacterial resistance was examined in relationship to antibiotic
      pharmacokinetics (PK) and organism MICs in the patients from four nosocomial
      lower respiratory tract infection clinical trials. The evaluable database
      included 107 acutely ill patients, 128 pathogens, and five antimicrobial
      regimens. Antimicrobial pharmacokinetics were characterized by using serum
      concentrations, and culture and sensitivity tests were performed daily on
      tracheal aspirates to examine resistance. Pharmacodynamic (PD) models were
      developed to identify factors associated with the probability of developing
      bacterial resistance. Overall, in 32 of 128 (25%) initially susceptible cases
      resistance developed during therapy. An initial univariate screen and a
      classification and regression tree analysis identified the ratio of the area
      under the concentration-time curve from 0 to 24 h to the MIC (AUC[0-24]/MIC) as a
      significant predictor of the development of resistance (P < 0.001). The final
      PK/PD model, a variant of the Hill equation, demonstrated that the probability of
      developing resistance during therapy increased significantly when antimicrobial
      exposure was at an AUC[0-24]/MIC ratio of less than 100. This relationship was
      observed across all treatments and within all organism groupings, with the
      exception of beta-lactamase-producing gram-negative organisms (consistent with
      type I beta-lactamase producers) treated with beta-lactam monotherapy.
      Combination therapy resulted in much lower rates of resistance than monotherapy,
      probably because all of the combination regimens examined had an AUC[0-24]/MIC
      ratio in excess of 100. In summary, the selection of antimicrobial resistance
      appears to be strongly associated with suboptimal antimicrobial exposure, defined
      as an AUC[0-24]MIC ratio of less than 100.

PMID- 9517925
TI  - Ceftazidime-resistant Enterobacteriaceae isolates from three Polish hospitals:
      identification of three novel TEM- and SHV-5-type extended-spectrum beta
      lactamases.
AB  - Twelve ceftazidime-resistant isolates of the family Enterobacteriaceae (11
      Klebsiella pneumoniae isolates and 1 Escherichia coli isolate) were collected in
      1995 from three Polish hospitals located in different cities. All were identified
      as producers of extended-spectrum beta-lactamases (ESBLs). Detailed analysis of
      their beta-lactamase contents revealed that six of them expressed SHV-5-like
      ESBLs. The remaining six were found to produce three different TEM enzymes, each
      characterized by a pI value of 6.0 and specified by new combinations of amino
      acid substitutions. The amino acid substitutions compared to the TEM-1 beta
      lactamase sequence were Gly238Ser, Glu240Lys, and Thr265Met for TEM-47; Leu21Phe,
      Gly238Ser, Glu240Lys, and Thr265Met for TEM-48; and Leu21Phe, Gly238Ser,
      Glu240Lys, Thr265Met, and Ser268Gly for TEM-49. The new TEM beta-lactamases, TEM
      47, TEM-48, and TEM-49, belong to a subfamily of TEM-2-related enzymes. Genes
      coding for TEM-47 and TEM-49 could have originated from the TEM-48-encoding
      sequence by various single genetic events. The new TEM derivatives probably
      document the already advanced microevolution of ESBLs ongoing in Polish
      hospitals, in a majority of which no monitoring of ESBL producers was performed
      before 1996.

PMID- 9517928
TI  - The gene encoding the low-affinity penicillin-binding protein 3r in Enterococcus
      hirae S185R is borne on a plasmid carrying other antibiotic resistance
      determinants.
AB  - Two plasmid-derived NcoI DNA fragments of 14 and 4.5 kb, respectively, have been
      isolated from the multidrug-resistant strain Enterococcus hirae S185R and
      analyzed. The 14-kb fragment contains two inverted (L and R) IS1216 insertion
      modules of the ISS1 family. These modules define a Tn5466 transposon-like
      structure that contains one copy of the methylase-encoding ermAM conferring
      erythromycin resistance and one copy of the adenylyl-transferase-encoding aadE
      conferring streptomycin resistance. Immediately on the left side of IS1216L there
      occurs a copy of pbp3r encoding the low-affinity penicillin-binding protein (PBP)
      PBP3r, itself preceded by a psr-like gene (psr3r) that controls the synthesis of
      PBP3r. ermAM, aadE, and the transposase gene (tnp) of IS1216R have the same
      polarities, and these are opposite those of psr3r, pbp3r, and the tnp gene of
      IS1216L. The 4.5-kb fragment is a copy of the 4.5-kb sequence at the 5' end of
      the 14-kb fragment, although it is not a restriction product of the 14-kb
      fragment. It contains three genes with the same polarity: psr3r, pbp3r, and tnp
      in an IS1216 element. Because of the very high degree of identity (99%) with the
      chromosomal psrfm and pbp5fm genes of Enterococcus faecium D63R, it is proposed
      that both the psr3r and pbp3r genes were transferred from an E.faecium strain and
      inserted in a plasmid of E. hirae. E. hirae is the first known bacterial species
      in which a low-affinity PBP-encoding gene has been found to be plasmid borne.

PMID- 9517929
TI  - In vitro antimalarial activity of a new organometallic analog, ferrocene
      chloroquine.
AB  - The in vitro activities of new organometallic chloroquine analogs, based on 4
      amino-quinoleine compounds bound to a molecule of ferrocene, were evaluated
      against chloroquine-susceptible, chloroquine-intermediate, and chloroquine
      resistant, culture-adapted Plasmodium falciparum lineages by a proliferation
      test. One of the ferrocene analogs totally restored the activity of chloroquine
      against chloroquine-resistant parasites. This compound, associated with tartaric
      acid for better solubility, was highly effective. The role of the ferrocene in
      reversing chloroquine resistance is discussed, as is its potential use for human
      therapy.

PMID- 9517930
TI  - Prophylactic anti-infective activity of poly-[1-6]-beta-D-glucopyranosyl-[1-3]
      beta-D-glucopryanose glucan in a guinea pig model of staphylococcal wound
      infection.
AB  - The judicious use of perioperative antibiotic prophylaxis reduces the infectious
      complications of surgery. However, increased bacterial resistance within
      hospitals may make antibiotic prophylaxis less effective in the future and
      alternative strategies are needed. New immunomodulatory agents might prevent
      wound infections by stimulation of the host immune system. To test this
      hypothesis, we administered poly-[1-6]-beta-D-glucopyranosyl- [1-3] -beta-D
      glucopyranose glucan (PGG glucan), which enhances neutrophil microbicidal
      activity, intravenously to guinea pigs in doses ranging from 0.015 to 4 mg/kg of
      body weight on the day before, on the day of, and on the day after intermuscular
      inoculation with methicillin-resistant strains of Staphylococcus aureus and
      Staphylococcus epidermidis. Abscesses were identified at 72 h, and median
      infective doses (ID50) and statistical significance were determined by logistic
      regression. Guinea pigs receiving PGG glucan and inoculated with methicillin
      resistant S. aureus and S. epidermidis exhibited ID50 of as much as 2.5- and 60
      fold higher, respectively, than those of control guinea pigs not receiving PGG
      glucan. Maximal protection was observed with a dose of 1 mg of PGG glucan per kg,
      and efficacy was reduced at higher as well as at lower PGG glucan doses.
      Furthermore, a single dose of PGG glucan given 24 h following bacterial
      inoculation was found to be effective in preventing infection. We conclude that
      PGG glucan reduces the risk of staphylococcal abscess formation. Neutrophil
      activating agents are a novel means of prophylaxis against surgical infection and
      may be less likely than antibiotics to be affected adversely by the increasing
      antibiotic resistance of nosocomial pathogens.

PMID- 9517931
TI  - Rifampin increases cytokine-induced expression of the CD1b molecule in human
      peripheral blood monocytes.
AB  - In recent years, it has been shown that a nonclassical, major histocompatibility
      complex-independent system (i.e., CD1-restricted T-cell responses) is involved in
      T-cell immunity against nonpeptide antigens. The CD1 system appears to function
      by presenting microbial lipid antigens to specific T cells, and the antigens so
      far identified include several known constituents of mycobacterial cell walls.
      Among the four known human CD1 isoforms, the CD1b protein is the best
      characterized with regard to its antigen-presenting function. Expression of CD1b
      is upregulated on human blood monocytes upon exposure to granulocyte/macrophage
      colony stimulating factor, alone or in combination with interleukin-4 (IL-4) (S.
      A. Porcelli, Adv. Immunol. 59:1-98, 1995). Rifampin (RFP) and its derivatives are
      widely used for chemoprophylaxis or chemotherapy against Mycobacterium
      tuberculosis. However, this agent was found to reduce the mitogen responsiveness
      of human B and T lymphocytes, chemotaxis, and delayed-type hypersensitivity. The
      present study extends the immunopharmacological profile of RFP by examining its
      effects on CD1b expression by human peripheral blood monocytes exposed to GM-CSF
      plus IL-4. The results showed that clinically attainable concentrations (i.e., 2
      or 10 microg/ml for 24 h) of the agent produced a marked increase in CD1b
      expression on the plasma membrane, as evaluated by fluorescence-activated cell
      sorter analysis, whereas it had no effect on cytosolic fractions, as indicated by
      Western blot analysis. This was found to be the result of increased CD1b gene
      expression, as shown by Northern blot analysis of CD1b mRNA. These results
      suggest that RFP could be of potential value in augmenting the CD1b-restricted
      antigen recognition system, thereby enhancing protective cellular immunity to M.
      tuberculosis.

PMID- 9517932
TI  - In vitro and in vivo antibacterial activities of CS-834, a new oral carbapenem.
AB  - CS-834 is a prodrug of the carbapenem R-95867, developed by Sankyo Co., Ltd.,
      Tokyo, Japan. To investigate the possibility that CS-834 may be the first
      carbapenem usable in an oral dosage form, its in vitro antibacterial activity (as
      R-95867) and in vivo antibacterial activity were compared with those of
      cefpodoxime proxetil, cefditoren pivoxil, cefdinir, ofloxacin, imipenem, and
      amoxicillin. R-95867 had high levels of activity against methicillin-susceptible
      staphylococci and streptococci, including penicillin-resistant Streptococcus
      pneumoniae, as well as Neisseria gonorrhoeae, Moraxella catarrhalis, the members
      of the family Enterobacteriaceae (with the exception of Serratia marcescens),
      Haemophilus influenzae, and Bordetella pertussis; for all these strains, the MICs
      at which 90% of tested strains are inhibited (MIC90s) were 1.0 microg/ml or less.
      Against methicillin-resistant staphylococci, enterococci, Serratia marcescens,
      Burkholderia cepacia, Stenotrophomonas maltophilia, and Acinetobacter
      calcoaceticus, R-95867 showed activity comparable to or slightly less than that
      of imipenem, with MIC90s ranging from 2 to >128 microg/ml. The in vivo efficacy
      of oral CS-834 against experimental mouse septicemia caused by gram-positive and
      gram-negative bacteria was better than that of comparative drugs. In murine
      respiratory infection models, the efficacy of CS-834 reflected not only its
      potent in vitro activity but also the high levels present in the lungs.

PMID- 9517933
TI  - Introduction of the mec element (methicillin resistance) into Staphylococcus
      aureus alters in vitro functional activities of fibrinogen and fibronectin
      adhesins.
AB  - Some methicillin-resistant strains of Staphylococcus aureus are defective in the
      production of major surface components such as protein A, clumping factor, or
      other important adhesins to extracellular matrix components which may play a role
      in bacterial colonization and infection. To evaluate the impact of methicillin
      resistance (mec) determinants on bacterial adhesion mediated by fibrinogen or
      fibronectin adhesins, we compared the in vitro attachment of two genetically
      distinct susceptible strains (NCTC8325 and Newman) to protein-coated surfaces
      with that of isogenic methicillin-resistant derivatives. All strains containing
      an intact mec element in their chromosomes were found to be defective in adhesion
      to fibrinogen and fibronectin immobilized on polymethylmethacrylate coverslips,
      regardless of the presence or absence of additional mutations in the femA, femB,
      or femC gene, known to decrease expression of methicillin resistance in S.
      aureus. Western ligand affinity blotting or immunoblotting of cell wall
      associated adhesins revealed similar contents of fibrinogen- or fibronectin
      binding proteins in methicillin-resistant strains compared to those of their
      methicillin-susceptible counterparts. In contrast to methicillin-resistant
      strains carrying a mec element in their genomes, methicillin-resistant strains
      constructed in vitro, by introducing the mecA gene on a plasmid, retained their
      adhesion phenotypes. In conclusion, the chromosomal insertion of the mec element
      into genetically defined strains of S. aureus impairs the in vitro functional
      activities of fibrinogen or fibronectin adhesins without altering their
      production. This effect is unrelated to the activity of the mecA gene.

PMID- 9517934
TI  - Effects of bicyclomycin on RNA- and ATP-binding activities of transcription
      termination factor Rho.
AB  - Bicyclomycin is a commercially important antibiotic that has been shown to be
      effective against many gram-negative bacteria. Genetic and biochemical evidence
      indicates that the antibiotic interferes with RNA metabolism in Escherichia coli
      by inhibiting the activity of transcription termination factor Rho. However, the
      precise mechanism of inhibition is not completely known. In this study we have
      used in vitro transcription assays to analyze the effects of bicyclomycin on the
      termination step of transcription. The Rho-dependent transcription termination
      region located within the hisG cistron of Salmonella typhimurium has been used as
      an experimental system. The possible interference of the antibiotic with the
      various functions of factor Rho, such as RNA binding at the primary site, ATP
      binding, and hexamer formation, has been investigated by RNA gel mobility shift,
      photochemical cross-linking, and gel filtration experiments. The results of these
      studies demonstrate that bicyclomycin does not interfere with the binding of Rho
      to the loading site on nascent RNA. Binding of the factor to ATP is not impeded,
      on the contrary, the antibiotic appears to decrease the apparent equilibrium
      dissociation constant for ATP in photochemical cross-linking experiments. The
      available evidence suggests that this decrease might be due to an interference
      with the correct positioning of ATP within the nucleotide-binding pocket leading
      b an inherent block of ATP hydrolysis. Possibly, as a consequence of this
      interference, the antibiotic also prevents ATP-dependent stabilization of Rho
      hexamers.

PMID- 9517935
TI  - Reduced clinical efficacy of pazufloxacin against gonorrhea due to high
      prevalence of quinolone-resistant isolates with the GyrA mutation. The
      Pazufloxacin STD Group.
AB  - Forty-two men with gonococcal urethritis were treated with an oral dosage of 200
      mg of pazufloxacin, a new fluoroquinolone, three times daily for 3 days. Only 28
      of the 42 men (66.7%) had negative culture results for Neisseria gonorrhoeae
      during follow-up. Of the 42 isolates, 41 could be recultured for antibiotic
      susceptibility testing and DNA sequencing. In 26 of the 41 isolates (63.4%), GyrA
      mutations with or without ParC mutations were identified. Among the 26 isolates,
      23 contained a single GyrA mutation, 1 contained two GyrA mutations, and 2
      contained three mutations including double GyrA and single ParC mutations. A
      single Ser-91-to-Phe mutation, which was detected in 14 of the 26 isolates, was
      the most common GyrA mutation, followed by an Ala-75 to Ser mutation and an Asp
      95 to Asn or Gly mutation in GyrA. All three isolates with two or three mutations
      contained the Ser-91-to-Phe GyrA mutation. Eleven of the 14 isolates with the
      single Ser-91-to-Phe mutation within GyrA and all 3 isolates with two or three
      mutations persisted after pazufloxacin treatment. On the other hand, all 15 wild
      type and 9 mutant isolates with a substitution at codon Ala-75 or Asp-95 were
      eradicated. The mean MIC of pazufloxacin for mutants with the single Ser-91-to
      Phe mutation in GyrA was 66-fold higher than that for the wild type. The results
      obtained in this study suggest that a high prevalence of fluoroquinolone
      resistant gonococcal isolates with the Ser-91-to-Phe mutation in GyrA reduced the
      efficacy of pazufloxacin as treatment for gonococcal urethritis.

PMID- 9517936
TI  - Covalent polymyxin B conjugate with human immunoglobulin G as an antiendotoxin
      reagent.
AB  - Polymyxin B (PMB) is a cyclic decapeptide antibiotic which also binds and
      neutralizes endotoxin. Unfortunately, PMB can be considerably nephrotoxic at
      clinically utilized doses, thereby limiting its utility as a therapeutic
      antiendotoxin reagent. We sought to change the pharmacokinetics and toxicity
      profile of PMB by covalently linking it to a human immunoglobulin G (IgG)
      carrier. Conjugates of PMB with IgG were prepared by EDAC [1-ethyl-3-(3
      dimethylaminopropyl) carbodiimide]-mediated amide formation. Analysis by dot
      enzyme-linked immunosorbent assay with an anti-PMB monoclonal antibody showed
      that the purified conjugate contained bound PMB. The IgG-PMB conjugate reacted
      with lipid A and J5 lipopolysaccharide in Western blot assays in a manner
      comparable to that of whole antiserum with anti-lipid A reactivity; unconjugated
      IgG had no reactivity. The PMB bound in the conjugate retained its endotoxin
      neutralizing activity compared to that of unbound PMB as evidenced by its dose
      dependent inhibition of tumor necrosis factor release by endotoxin-stimulated
      human monocytes in vitro; unconjugated IgG had no activity. By this assay, the
      PMB-IgG conjugate was determined to have approximately 3.0 microg of bound
      functional PMB per 100 microg of total protein of conjugate (five molecules of
      PMB per IgG molecule). The PMB-IgG conjugate was also bactericidal against
      clinical strains of Escherichia coli, Pseudomonas aeruginosa, and Klebsiella
      pneumoniae relative to unconjugated IgG with MBCs of <4 microg of conjugate per
      ml for each of the tested strains. The conjugate appeared to be nontoxic at the
      highest doses deliverable and provided statistically significant protection from
      death to galactosamine-sensitized, lipopolysaccharide-challenged mice in a dose
      dependent fashion when administered prophylactically 2 h before challenge.
      However, neither free PMB nor the PMB-IgG conjugate could protect mice challenged
      with endotoxin 2 h after administration. This suggests that these reagents can
      play a role in prophylaxis but not in therapy of sepsis. These experiments
      demonstrated that the PMB-IgG conjugate retains bound yet functional PMB as
      evidenced by its endotoxin-neutralizing activity both in vitro and in vivo.
      Further work is required to define the role that this or related conjugate
      compounds may play in the prophylaxis of endotoxin-mediated disease.

PMID- 9517937
TI  - Prevalence of antimicrobial-resistant pathogens in middle ear fluid:
      multinational study of 917 children with acute otitis media.
AB  - The management of acute otitis media is complicated by the emergence of
      resistance to beta-lactam and other antibiotics among common pathogens. We
      conducted a large, international study of infants and children with acute otitis
      media to identify pathogens and susceptibility patterns. During the winter of
      1994 to 1995, middle ear fluid samples were collected from 917 patients with
      acute otitis media in Bulgaria, the Czech Republic, Hungary, Romania, Slovakia,
      Israel, and the United States. A single reference laboratory performed in vitro
      susceptibility testing. Pathogens were isolated from 62% of the patients. For
      Streptococcus pneumoniae (30% of the patients), untypeable Haemophilus influenzae
      (17%), and Moraxella catarrhalis (4%), there was significant variation among
      geographic regions (P < 0.001). The composite susceptibilities of these three
      organisms to amoxicillin ranged from 62% in the United States to 89% in Eastern
      and Central Europe; the corresponding susceptibilities to amoxicillin-clavulanate
      ranged from 90% in Israel to 95% in Eastern and Central Europe. beta-Lactamase
      was produced by 31 and 100% of the isolates of H. influenzae and M. catarrhalis,
      respectively. More isolates of S. pneumoniae were susceptible to amoxicillin
      (90%) or amoxicillin-clavulanate (90%) than to penicillin (70%; P = 0.002). The
      prevalence of resistant S. pneumoniae was highest in patients less than 12 months
      of age. S. pneumoniae, H. influenzae, and M. catarrhalis remain the most
      important bacterial pathogens in patients with acute otitis media; however, their
      prevalence is variable and resistance patterns are changing.

PMID- 9517938
TI  - Plasmid-mediated resistance to expanded-spectrum cephalosporins among
      Enterobacter aerogenes strains.
AB  - Resistance to expanded-spectrum cephalosporins commonly develops in Enterobacter
      aerogenes during therapy due to selection of mutants producing high levels of the
      chromosomal Bush group 1 beta-lactamase. Recently, resistant strains producing
      plasmid-mediated extended-spectrum beta-lactamases (ESBLs) have been isolated as
      well. A study was designed to investigate ESBL production among 31 clinical
      isolates of E. aerogenes from Richmond, Va., with decreased susceptibility to
      expanded-spectrum cephalosporins and a positive double-disk potentiation test.
      Antibiotic susceptibility was determined by standard disk diffusion and agar
      dilution procedures. Beta-lactamases were investigated by an isoelectric focusing
      overlay technique which simultaneously determined isoelectric points (pIs) and
      substrate or inhibitor profiles. Decreased susceptibility to cefotaxime,
      ceftazidime, and aztreonam (MIC range, 1 to 64 microg/ml) was detected and
      associated with resistance to gentamicin and trimethoprim-sulfamethoxazole. All
      strains produced an inducible Bush group 1 beta-lactamase (pI 83). Twenty-nine of
      the 31 isolates also produced an enzyme similar to SHV-4 (pI 7.8), while 1
      isolate each produced an enzyme similar to SHV-3 (pI 6.9) and to SHV-5 (pI 8.2).
      The three different SHV-derived ESBLs were transferred by transconjugation to
      Escherichia coli C600N and amplified by PCR. Plasmid profiles of the clinical
      isolates showed a variety of different large plasmids. Because of the linkage of
      resistance to aminoglycosides and trimethoprim-sulfamethoxazole with ESBL
      production, it is possible that the usage of these drugs was responsible for
      selecting plasmid-mediated resistance to extended-spectrum cephalosporins in E.
      aerogenes. Furthermore, it is important that strains such as these be recognized,
      because they can be responsible for institutional spread of resistance genes.

PMID- 9517939
TI  - Oxfendazole treatment for cystic hydatid disease in naturally infected animals.
AB  - Few chemotherapeutic agents are available for the medical management of hydatid
      disease caused by the parasite Echinococcus granulosus. In order to test the
      potential of oxfendazole for the treatment of infection with this parasite, nine
      infected goats and four sheep were given oxfendazole twice weekly at a dose of 30
      mg/kg of body weight for 4 weeks and monitored by ultrasound for an additional 4
      weeks. Efficacy was finally evaluated by postmortem examination, including
      determination of protoscolex viability and cyst wall histology. In treated
      animals, protoscolices were dead or absent in 97% of cysts from oxfendazole
      treated animals compared to 28% of cysts from untreated control animals. On
      postmortem examination, 53% of cysts from treated animals were found to be
      grossly degenerate. A sample of those cysts that appeared potentially viable all
      demonstrated evidence of severe damage to the cyst wall. By light microscopy,
      cysts showed severe disorganization of the adventitial layer with invasion of
      inflammatory cells and in some cases frank necrosis with no apparent adventitial
      layer. The follow-up period for assessment of the drug's ability to cause
      complete degeneration and resorption of cysts was relatively short. This study,
      however, indicates that oxfendazole is at least as effective as and is easier to
      administer than albendazole for the treatment of hydatid disease.

PMID- 9517941
TI  - Anti-human immunodeficiency virus activity and cellular metabolism of a potential
      prodrug of the acyclic nucleoside phosphonate 9-R-(2
      phosphonomethoxypropyl)adenine (PMPA), Bis(isopropyloxymethylcarbonyl)PMPA.
AB  - Bis(isopropyloxymethylcarbonyl) 9-R-(2-phosphonomethoxypropyl)adenine
      [bis(POC)PMPA] has been identified as a novel prodrug of PMPA. The anti-human
      immunodeficiency virus activity of bis(POC)PMPA was >100-fold greater than that
      of PMPA in both an established T-cell line and primary peripheral blood
      lymphocytes. This improved efficacy was shown to be due to a rapid intracellular
      uptake of the prodrug resulting in an increased intracellular accumulation of
      PMPA diphosphate (PMPApp), the pharmacologically active metabolite. PMPApp levels
      in bis(POC)PMPA-treated cells exceeded by >1,000-fold the levels seen in cells
      treated with unmodified PMPA in both resting and activated peripheral blood
      lymphocytes. Significant differences in the intracellular catabolism of PMPA
      metabolites were noted between the resting and activated lymphocytes. The half
      life for the disappearance of PMPApp, derived from either bis(POC)PMPA or PMPA,
      was 12 to 15 h in the activated lymphocytes and 33 to 50 h in the resting
      lymphocytes. This long persistence of PMPApp, particularly in resting
      lymphocytes, may be unique to the nucleoside phosphonate analogs and indicates
      that effective levels of the active metabolite can be achieved and maintained
      with relatively infrequent administration of the parent drug.

PMID- 9517940
TI  - Treatment of invasive fungal infections in renally impaired patients with
      amphotericin B colloidal dispersion.
AB  - Amphotericin B colloidal dispersion (ABCD) is a new formulation of conventional
      amphotericin B designed to minimize drug distribution in the kidney and reduce
      nephrotoxicity. We studied the safety and efficacy of ABCD in 133 renally
      compromised patients with invasive fungal infections. Patients had either
      nephrotoxicity from amphotericin B or preexisting renal disease. Intravenous
      treatment with ABCD (4 mg/kg of body weight daily) was administered for up to 6
      weeks. Evaluations included clinical response to treatment and adverse events,
      with emphasis on changes in serum creatinine levels. ABCD did not appear to have
      an adverse effect on renal function: mean serum creatinine level tended to
      decrease slightly with days on therapy, and increases were not dose related.
      Complete or partial response to treatment was reported for 50% of the 133 intent
      to-treat patients and 67% of the 58 evaluable patients.

PMID- 9517942
TI  - 1,1,3-Trioxo-2H,4H-thieno[3,4-e][1,2,4]thiadiazine (TTD) derivatives: a new class
      of nonnucleoside human immunodeficiency virus type 1 (HIV-1) reverse
      transcriptase inhibitors with anti-HIV-1 activity.
AB  - We report the development of a new group of nonnucleoside reverse transcriptase
      inhibitors (NNRTIs). One of the most active congeners of this series of 1,1,3
      trioxo-2H,4H-thieno[3,4-e] [1,2,4]thiadiazine (TTD) derivatives, i.e., 2-(3
      fluorobenzyl)-4-cyanomethylen-l,1,3-trioxo-2H,4H- thieno [3,4-e] [1,2,4]
      thiadiazine) (QM96639) was found to inhibit human immunodeficiency virus (HIV)
      type 1 [HIV-1 (IIIB)] replication in MT-4 cells at a concentration of 0.09
      microM. This compound was toxic for the host cells only at a 1,400-fold higher
      concentration. The TTD derivatives proved effective against a variety of HIV-1
      strains, including those that are resistant to 3'-azido-3'-deoxythymidine (AZT),
      but not against HIV-2 (ROD) or simian immunodeficiency virus (SIV/ MAC251). HIV-1
      strains containing the L100I, K103N, V106A, E138K, Y181C, or Y188H mutations in
      their reverse transcriptase (RT) displayed reduced sensitivity to the compounds.
      Their cross-resistance patterns correlated with that of nevirapine. 2-Benzyl-4
      cyanomethylen-1,1,3-trioxo-2H,4H-thieno[3,4-e] [1,2,4]thiadiazine (QM96521)
      enhanced the anti-HIV-1 activity of AZT and didanosine in a subsynergistic
      manner. HIV-1-resistant virus containing the V179D mutation in the RT was
      selected after approximately six passages of HIV-1 (IIIB) in CEM cells in the
      presence of different concentrations of QM96521. From structure-activity
      relationship analysis of a wide variety of TTD derivatives, a number of
      restrictions appeared as to the chemical modifications that were compatible with
      anti-HIV activity. Modelling studies suggest that in contrast to most other
      NNRTIs, but akin to nevirapine, QM96521 does not act as a hydrogen bond donor in
      the RT-drug complex.

PMID- 9517943
TI  - Susceptibilities of penicillin- and erythromycin-susceptible and -resistant
      pneumococci to HMR 3647 (RU 66647), a new ketolide, compared with
      susceptibilities to 17 other agents.
AB  - Susceptibility of 230 penicillin- and erythromycin-susceptible and -resistant
      pneumococci to HMR 3647 (RU 66647), a new ketolide, was tested by agar dilution,
      and results were compared with those of erythromycin, azithromycin,
      clarithromycin, roxithromycin, rokitamycin, clindamycin, pristinamycin,
      ciprofloxacin, sparfloxacin, trimethoprim-sulfamethoxazole, doxycycline,
      chloramphenicol, cefuroxime, ceftriaxone, imipenem, and vancomycin. HMR 3647 was
      very active against all strains tested, with MICs at which 90% of the strains
      were inhibited (MIC90s) of 0.03 microg/ml for erythromycin-susceptible strains
      (MICs, < or =0.25 microg/ml) and 0.25 microg/ml for erythromycin-resistant
      strains (MICs, > or =1.0 microg/ml). All other macrolides yielded MIC90s of 0.03
      to 0.25 and >64.0 microg/ml for erythromycin-susceptible and -resistant strains,
      respectively. The MICs of clindamycin for 51 of 100 (51%) erythromycin-resistant
      strains were < or =0.125 microg/ml. The MICs of pristinamycin for all strains
      were < or =1.0 microg/ml. The MIC90s of ciprofloxacin and sparfloxacin were 4.0
      and 0.5 microg/ml, respectively, and were unaffected by penicillin or
      erythromycin susceptibility. Vancomycin and imipenem inhibited all strains at <
      or =1.0 microg/ml. The MICs of cefuroxime and cefotaxime rose with those of
      penicillin G. The MICs of trimethoprim-sulfamethoxazole, doxycycline, and
      chloramphenicol were variable but were generally higher in penicillin- and
      erythromycin-resistant strains. HMR 3647 had the best kill kinetics of all
      macrolides tested against 11 erythromycin-susceptible and -resistant strains,
      with uniform bactericidal activity (99.9% killing) after 24 h at two times the
      MIC and 99% killing of all strains at two times the MIC after 12 h for all
      strains. Pristinamycin showed more rapid killing at 2 to 6 h, with 99.9% killing
      of 10 of 11 strains after 24 h at two times the MIC. Other macrolides showed
      significant activity, relative to the MIC, against erythromycin-susceptible
      strains only.

PMID- 9517944
TI  - Tolerance and pharmacokinetic interactions of rifabutin and clarithromycin in
      human immunodeficiency virus-infected volunteers.
AB  - This study evaluated the tolerance and potential pharmacokinetic interactions
      between clarithromycin (500 mg every 12 h) and rifabutin (300 mg daily) in
      clinically stable human immunodeficiency virus-infected volunteers with CD4
      counts of <200 cells/mm3. Thirty-four subjects were randomized equally to either
      regimen A or regimen B. On days 1 to 14, subjects assigned to regimen A received
      clarithromycin and subjects assigned to regimen B received rifabutin, and then
      both groups received both drugs on days 15 to 42. Of the 14 regimen A and the 15
      regimen B subjects who started combination therapy, 1 subject in each group
      prematurely discontinued therapy due to toxicity, but 19 of 29 subjects reported
      nausea, vomiting, and/or diarrhea. Pharmacokinetic analysis included data for 11
      regimen A and 14 regimen B subjects. Steady-state pharmacokinetic parameters for
      single-agent therapy (day 14) and combination therapy (day 42) were compared.
      Regimen A resulted in a mean decrease of 44% (P = 0.003) in the clarithromycin
      area under the plasma concentration-time curve (AUC), while there was a mean
      increase of 57% (P = 0.004) in the AUC of the clarithromycin metabolite 14-OH
      clarithromycin. Regimen B resulted in a mean increase of 99% (P = 0.001) in the
      rifabutin AUC and a mean increase of 375% (P < 0.001) in the AUC of the rifabutin
      metabolite 25-O-desacetyl-rifabutin. The usefulness of this combination for
      prophylaxis of Mycobacterium avium infections is limited by frequent
      gastrointestinal adverse events. Coadministration of clarithromycin and rifabutin
      results in significant bidirectional pharmacokinetic interactions. The resulting
      increase in rifabutin levels may explain the increased frequency of uveitis
      observed with concomitant use of these drugs.

PMID- 9517945
TI  - Oral administration of a prodrug of the influenza virus neuraminidase inhibitor
      GS 4071 protects mice and ferrets against influenza infection.
AB  - We have recently described GS 4071, a carbocyclic transition-state analog
      inhibitor of the influenza virus neuraminidase, which has potent inhibitory
      activity comparable to that of 4-guanidino-Neu5Ac2en (GG167; zanamivir) when
      tested against influenza A virus replication and neuraminidase activity in vitro.
      We now report that GS 4071 is active against several strains of influenza A and B
      viruses in vitro and that oral GS 4104, an ethyl ester prodrug which is converted
      to GS 4071 in vivo, is active in the mouse and ferret models of influenza virus
      infection. Oral administration of 10 mg of GS 4104 per kg of body weight per day
      caused a 100-fold reduction in lung homogenate viral titers and enhanced survival
      in mice infected with influenza A or B viruses. In ferrets, a 25-mg/kg dose of GS
      4104 given twice daily reduced peak viral titers in nasal washings and eliminated
      constitutional responses to influenza virus infection including fever, increased
      nasal signs (sneezing, nasal discharge, mouth breathing), and decreased activity.
      Consistent with our demonstration that the parent compound is highly specific for
      influenza virus neuraminidases, no significant drug-related toxicity was observed
      after the administration of oral dosages of GS 4104 of up to 800 mg/kg/day for 14
      days in nonclinical toxicology studies with rats. These results indicate that GS
      4104 is a novel, orally active antiviral agent with the potential to be used for
      the prophylaxis and treatment of influenza A and B virus infections.

PMID- 9517946
TI  - Identification of GS 4104 as an orally bioavailable prodrug of the influenza
      virus neuraminidase inhibitor GS 4071.
AB  - GS 4071 is a potent carbocyclic transition-state analog inhibitor of influenza
      virus neuraminidase with activity against both influenza A and B viruses in
      vitro. GS 4116, the guanidino analog of GS 4071, is a 10-fold more potent
      inhibitor of influenza virus replication in tissue culture than GS 4071. In this
      study we determined the oral bioavailabilities of GS 4071, GS 4116, and their
      respective ethyl ester prodrugs in rats. Both parent compounds and the prodrug of
      the guanidino analog exhibited poor oral bioavailability (2 to 4%) and low peak
      concentrations in plasma (Cmaxs; Cmax <0.06 microg/ml). In contrast, GS 4104, the
      ethyl ester prodrug of GS 4071, exhibited good oral bioavailability (35%) as GS
      4071 and high Cmaxs of GS 4071 (Cmax = 0.47 microg/ml) which are 150 times the
      concentration necessary to inhibit influenza virus neuraminidase activity by 90%.
      The bioavailability of GS 4104 as GS 4071 was also determined in mice (30%),
      ferrets (11%), and dogs (73%). The plasma of all four species exhibited high,
      sustained concentrations of GS 4071 such that at 12 h postdosing the
      concentrations of GS 4071 in plasma exceeded those necessary to inhibit influenza
      virus neuraminidase activity by 90%. These results demonstrate that GS 4104 is an
      orally bioavailable prodrug of GS 4071 in animals and that it has the potential
      to be an oral agent for the prevention and treatment of influenza A and B virus
      infections in humans.

PMID- 9517947
TI  - Short- and long-term efficacy of hexadecylphosphocholine against established
      Leishmania infantum infection in BALB/c mice.
AB  - In the immunocompetent host, visceral leishmaniasis (VL) is a fatal disease if
      untreated. In immunosuppressed patients, VL is an opportunistic infection for
      which there is no effective treatment for relapses. Here we report on the long
      term activity of orally administered hexadecylphosphocholine (HDPC) against
      established Leishmania infantum infection in BALB/c mice. HDPC is a synthetic
      phospholipid with antiproliferative properties that has been extensively studied
      for its cancerostatic activity. Its short-term leishmanicidal effects in mice
      recently infected with viscerotropic Leishmania species have been previously
      reported. First, we show that 5 days of oral therapy with HDPC (20 mg/kg of body
      weight/day) led to amastigote suppression in the liver and the spleen of 94 and
      78%, respectively (versus 85 and 55% suppression by meglumine antimonate in the
      liver and spleen, respectively), in mice infected 6 weeks before treatment and
      examined 3 days after the end of treatment. These results demonstrate the short
      term efficacy of HDPC against an established Leishmania infection. Next, the long
      term efficacy of HDPC was examined. In HDPC-treated mice both the hepatic and
      splenic amastigote loads were significantly reduced (at least 89%) 10, 31, and 52
      days after the end of the treatment. In the treated mice, the increase of the
      splenic load was significantly slower than that in the untreated mice,
      demonstrating that the HDPC-exerted inhibition of Leishmania growth persisted for
      at least 7 to 8 weeks. Orally administered HDPC--the safe doses and side effects
      of which are at least partially known--appears to be a promising candidate for
      the treatment of VL.

PMID- 9517948
TI  - Inter- and intraquinolone predictors of antimicrobial effect in an in vitro
      dynamic model: new insight into a widely used concept.
AB  - Earlier efforts to search for pharmacokinetic and bacteriological predictors of
      fluoroquinolone antimicrobial effects (AMEs) have resulted in conflicting
      findings. To elucidate whether these conflicts are real or apparent, several
      predictors of the AMEs of two pharmacokinetically different antibiotics,
      trovafloxacin (TRO) and ciprofloxacin (CIP), as well as different dosing regimens
      of CIP were examined. The AMEs of TRO given once daily (q.d.) and CIP given q.d.
      and twice daily (b.i.d.) against Escherichia coli, Pseudomonas aeruginosa, and
      Klebsiella pneumoniae were studied in an in vitro dynamic model. Different
      monoexponential pharmacokinetic profiles were simulated with a TRO half-life of
      9.2 h and a CIP half-life of 4.0 h to provide similar eightfold ranges of the
      area under the concentration-time curve (AUC)-to-MIC ratios, from 54 to 432 and
      from 59 to 473 (microg x h/ml)/(microg/ml), respectively. In each case the
      observation periods were designed to incorporate full-term regrowth phases in the
      time-kill curves, and the AME was expressed by its intensity (IE; the area
      between the control growth and time-kill and regrowth curves up to the point at
      which the viable counts of regrowing bacteria are close to the maximum values
      observed without drug). Species-independent linear relationships were established
      between IE and log AUC/MIC, log AUC above MIC (log AUCeff), and time above the
      MIC (Teff). Specific and nonsuperimposed IE versus log AUC/MIC or log AUCeff
      relationships were inherent in each of the treatments: TRO given q.d. (r2 = 0.97
      and 0.96), CIP given q.d. (r2 = 0.98 and 0.96), and CIP given b.i.d. (r2 = 0.95
      and 0.93). This suggests that in order to combine data sets obtained with
      individual quinolones to examine potential predictors, one must be sure that
      these sets may be combined. Unlike AUC/MIC and AUCeff, the IE-Teff relationships
      plotted for the different quinolones and dosing regimens were nonspecific and
      virtually superimposed (r2 = 0.95). Hence, AUC/MIC, AUCeff and Teff were equally
      good predictors of the AME of each of the quinolones and each dosing regimen
      taken separately, whereas Teff was also a good predictor of the AMEs of the
      quinolones and their regimens taken together. However, neither the quinolones nor
      the dosing regimens could be distinguished solely on the basis of Teff whereas
      they could be distinguished on the basis of AUC/MIC or AUCeff. Thus, two types of
      predictors of the quinolone AME may be identified: intraquinolone and/or
      intraregimen predictors (AUC/MIC, AUCeff and Teff) and an interquinolone and
      interregimen predictor (Teff). Teff may be able to accurately predict the AME of
      one quinolone on the basis of the data obtained for another quinolone.

PMID- 9517950
TI  - Antibiotic treatment of experimental pneumonic plague in mice.
AB  - A mouse model was developed to evaluate the efficacy of antibiotic treatment of
      pneumonic plague; streptomycin was compared to antibiotics with which there is
      little or no clinical experience. Infection was induced by inhalation of
      aerosolized Yersinia pestis organisms. Antibiotics were administered by
      intraperitoneal injection every 6 hours for 5 days, at doses that produced levels
      of drug in serum comparable to those observed in humans treated for other serious
      infections. These studies compared in vitro to in vivo activity and evaluated the
      efficacy of antibiotics started at different times after exposure. Early
      treatment (started 24 h after challenge, when 0 of 10 mice tested had positive
      blood cultures) with netilmicin, ciprofloxacin, ofloxacin, ceftriaxone,
      ceftazidime, aztreonam, ampicillin, and rifampin (but not cefazolin, cefotetan,
      or ceftizoxime) demonstrated efficacy comparable to streptomycin. Late treatment
      (started 42 h after exposure, when five of five mice tested had positive blood
      cultures) with netilmicin, ciprofloxacin, ofloxacin, and a high dose (20 mg/kg of
      body weight every 6 h) of gentamicin produced survival rates comparable to that
      with streptomycin, while all of the beta-lactam antibiotics (cefazolin,
      cefotetan, ceftriaxone, ceftazidime, aztreonam, and ampicillin) and rifampin were
      significantly inferior to streptomycin. In fact, all groups of mice treated late
      with beta-lactam antibiotics experienced accelerated mortality rates compared to
      normal-saline-treated control mice. These studies indicate that netilmicin,
      gentamicin, ciprofloxacin, and ofloxacin may be alternatives for the treatment of
      pneumonic plague in humans. However, the beta-lactam antibiotics are not
      recommended, based upon poor efficacy in this mouse model of pneumonic plague,
      particularly when pneumonic plague may be associated with bacteremia.

PMID- 9517949
TI  - Anti-Pneumocystis activities of aromatic diamidoxime prodrugs.
AB  - Aromatic dicationic compounds, such as pentamidine, have potent antimicrobial
      activities. Clinical use of these compounds has been restricted, however, by
      their toxicity and limited oral activity. A novel approach, using amidoxime
      derivatives as prodrugs, has recently been proposed to overcome these
      limitations. Although results were presented for amidoxime derivatives of only
      one diamidine, pentamidine, the authors in the original proposal claimed that
      amidoxime derivatives would work as effective prodrugs for all pharmacologically
      active diamidines. Nine novel amidoxime derivatives were synthesized and tested
      in the present study for activity against Pneumocystis carinii in corticosteroid
      suppressed rats. Only three of the nine compounds had significant oral anti
      Pneumocystis activity. The bisbenzamidoxime derivatives of three direct
      pentamidine analogs had excellent oral and intravenous activities and reduced
      acute host toxicity. These compounds are not likely candidates for future drug
      development, however, because they have chronic toxic effects and the active
      amidine compounds have multiple sites susceptible to oxidative metabolism, which
      complicates their pharmacology and toxicology. Novel diamidoximes from three
      other structural classes, containing different groups linking the cationic
      moieties, lacked significant oral or intravenous anti-Pneumocystis activity, even
      though the corresponding diamidines were very active intravenously. Both active
      and inactive amidoximes were readily metabolized to the corresponding amidines by
      cell-free liver homogenates. Thus, the amidoxime prodrug approach may provide a
      strategy to exploit the potent antimicrobial and other pharmacological activities
      of selected, but certainly not all, aromatic diamidines.

PMID- 9517952
TI  - Pharmacokinetics and bioavailability of the anti-human immunodeficiency virus
      nucleotide analog 9-[(R)-2-(phosphonomethoxy)propyl]adenine (PMPA) in dogs.
AB  - The pharmacokinetics, bioavailability, and metabolism of the anti-human
      immunodeficiency virus nucleotide analog 9[(R)-2-(phosphonomethoxy)propyl]adenine
      (PMPA) were determined in beagle dogs following intravenous, intraperitoneal, and
      oral administration. Fasted male beagle dogs (n = 5) were pretreated with
      pentagastrin and received PMPA (10 mg/kg of body weight) by the intravenous and
      oral routes with a washout period of 1 week between doses. A further group of
      male dogs received PMPA as a single dose via the intravenous (1 mg/kg; n = 5) and
      the intraperitoneal (10 mg/kg; n = 3) routes, with 1-week washout period between
      doses. The concentrations of PMPA in plasma and urine were determined over 48 h
      postdosing by fluorescence derivatization and high-performance liquid
      chromatography (HPLC). The potential for metabolism or biliary excretion of PMPA
      was evaluated in a dog with a chronic indwelling bile cannula. Urine, feces, and
      bile were collected at intervals over 48 h following the intravenous
      administration of [14C]PMPA (10 mg/kg; 55 microCi/kg). The concentrations of PMPA
      in plasma after intravenous injection were best described by an open two
      compartment model with a terminal half-life of approximately 10 h. PMPA was
      excreted unchanged in urine (70%); recovery in feces (0.42%) or bile (0.26%) was
      negligible. The plasma clearance of PMPA (0.28+/-0.05 liter/h/kg) was
      substantially greater than the glomerular filtration rate in this species,
      suggesting active tubular secretion of PMPA. No metabolites of [14C]PMPA were
      observed in urine, feces, or bile on the basis of HPLC with radioactive flow
      detection. The remainder of the dose was probably excreted unchanged in urine
      beyond 48 h postdosing. The mean+/-standard deviation observed bioavailabilities
      of PMPA following oral and intraperitoneal administration at 10 mg/kg were
      17.1%+/-1.88% and 73.5%+/-10.5%, respectively.

PMID- 9517951
TI  - Relationship between antimalarial drug activity, accumulation, and inhibition of
      heme polymerization in Plasmodium falciparum in vitro.
AB  - We have investigated the contribution of drug accumulation and inhibition of heme
      polymerization to the in vitro activities of a series of antimalarial drugs. Only
      those compounds exhibiting structural relatedness to the quinolines inhibited
      heme polymerization. We could find no direct correlation between in vitro
      activity against chloroquine-susceptible or chloroquine-resistant isolates and
      either inhibition of heme polymerization or cellular drug accumulation for the
      drugs studied. However, in vitro activity against a chloroquine-susceptible
      isolate but not a chloroquine-resistant isolate showed a significant correlation
      with inhibition of heme polymerization when the activity was normalized for the
      extent of drug accumulation. The importance of these observations to the rational
      design of new quinoline-type drugs and the level of agreement of these
      conclusions with current views on quinoline drug action and resistance are
      discussed.

PMID- 9517953
TI  - Neurotoxicodynamics of the interaction between ciprofloxacin and foscarnet in
      mice.
AB  - The potential for convulsions induced by the coadministration of ciprofloxacin
      (CPFX) and foscarnet (PFA) may be due not to a change in the distribution of CPFX
      to the brain but to a potential CPFX-induced inhibition of gamma-aminobutyric
      acid (GABA)-GABA(A) receptor binding in the presence of PFA.

PMID- 9517955
TI  - In vitro activities of quinupristin-dalfopristin and the streptogramin RPR 106972
      against Mycoplasma pneumoniae.
AB  - The in vitro activities of quinupristin-dalfopristin and streptogramin RPR 106972
      were determined with 44 strains of Mycoplasma pneumoniae and compared to those of
      macrolides, minocycline, and quinolones. All isolates tested were highly
      susceptible to macrolides and to quinupristin-dalfopristin (MIC at which 90% of
      the isolates are inhibited [MIC90], 0.0625 microg/ml), followed by RPR 106972
      (MIC90, 0.5 microg/ml), quinolones, and minocycline.

PMID- 9517954
TI  - Effect of terbinafine on theophylline pharmacokinetics in healthy volunteers.
AB  - Twelve healthy volunteers were enrolled in an open-label, randomized, crossover
      study. Subjects received single doses of theophylline (5 mg/kg) with and without
      multiple-dose terbinafine, and 11 blood samples were collected over 24 h. The
      study phases were separated by a 4-week washout period. Theophylline serum data
      were modeled via noncompartmental analysis. When the control phase (i.e., no
      terbinafine) was compared to the treatment phase (terbinafine), theophylline
      exposure (the area under the serum concentration-time curve from time zero to
      infinity) increased by 16% (P = 0.03), oral clearance decreased by 14% (P =
      0.04), and half-life increased by 24% (P = 0.002). No significant changes in
      other theophylline pharmacokinetic parameters were evident.

PMID- 9517956
TI  - Antimicrobial activity of novel furanonaphthoquinone analogs.
AB  - Analogs of furanonaphthoquinone (FNQ) from Tecoma ipe Mart had MICs ranging from
      1.56 to 25 microg/ml against gram-positive bacteria. FNQ showed significantly
      lower MICs against methicillin-resistant Staphylococcus aureus than against
      methicillin-sensitive S. aureus. FNQ inhibited Helicobacter pylori with an MIC of
      0.1 microg/ml. Fungi, including pathogenic species, were sensitive to FNQ with
      MICs similar to those of amphotericin B.

PMID- 9517957
TI  - In vitro activity of BAY 12-8039, a new fluoroquinolone against mycoplasmas.
AB  - The in vitro activity of the fluoroquinolone BAY 12-8039 against 66 strains of
      different mycoplasma species and 30 strains of Ureaplasma urealyticum was
      compared with those of three other antimicrobial agents. BAY 12-8039 at 0.5
      microg/ml inhibited 100% of all the mycoplasmal and ureaplasmal strains tested.
      The minimal bactericidal concentrations of BAY 12-8039 increased only two- to
      eightfold compared to the MICs. Furthermore, they were comparable to those of
      sparfloxacin and lower than those of doxycycline and clarithromycin.

PMID- 9517959
TI  - Role of superoxide in catalase-peroxidase-mediated isoniazid action against
      mycobacteria.
AB  - Isoniazid (INH) activation in vitro is associated with reduction of the
      mycobacterial ferric KatG catalase-peroxidase by hydrazine and reaction with O2
      to form an oxyferrous enzyme complex. Since this complex could also form directly
      via reaction of ferric KatG with superoxide, intracellular activation might be
      responsive to superoxide concentration. When Mycobacterium smegmatis carrying the
      M. bovis katG gene was treated with nontoxic levels of plumbagin, a generator of
      superoxide, the bacteriostatic activity of INH increased unless a plasmid-borne
      superoxide dismutase gene was also present. Thus, endogenous superoxide probably
      contributes to intracellular activation of INH.

PMID- 9517958
TI  - Antimicrobial resistance in enterococci isolated from Turkey flocks fed
      virginiamycin.
AB  - From 125 separate cloacal cultures from three turkey flocks fed virginiamycin,
      104 Enterococcus faecium and 186 Enterococcus faecalis isolates were obtained. As
      the turkeys aged, there was a higher percentage of quinupristin-dalfopristin
      resistant E. faecium isolates, with isolates from the oldest flock being 100%
      resistant. There were no vancomycin-resistant enterococci. Results of pulsed
      field gel electrophoresis (PFGE) indicated there were 11 PFGE types of E.
      faecalis and 7 PFGE types of E. faecium that were in more than one group of flock
      cultures.

PMID- 9517960
TI  - Activities of isoniazid alone and in combination with other drugs against
      Mycobacterium avium infection in beige mice.
AB  - Monotherapy with isoniazid or amikacin or clarithromycin or combinations of two
      of these drugs showed nil to modest therapeutic activity in beige mice infected
      with Mycobacterium avium. However, the combination of all three, isoniazid
      amikacin-clarithromycin, markedly reduced CFUs in both spleens and lungs after 91
      days of infection.

PMID- 9517961
TI  - The antibiotic micrococcin is a potent inhibitor of growth and protein synthesis
      in the malaria parasite.
AB  - The antibiotic micrococcin is a potent growth inhibitor of the human malaria
      parasite Plasmodium falciparum, with a 50% inhibitory concentration of 35 nM.
      This is comparable to or less than the corresponding levels of commonly used
      antimalarial drugs. Micrococcin, like thiostrepton, putatively targets protein
      synthesis in the plastid-like organelle of the parasite.

PMID- 9517962
TI  - Analysis of diversity of mutations in the mecI gene and mecA promoter/operator
      region of methicillin-resistant Staphylococcus aureus and Staphylococcus
      epidermidis.
AB  - Genomic diversity of mutation in the mecI gene or mecA promoter/operator region
      was analyzed for clinical isolates of methicillin-resistant Staphylococcus aureus
      (MRSA) and Staphylococcus epidermidis (MRSE). In most MRSA strains, a single base
      substitution was detected in either the mecI (three different positions) or the
      mecA promoter (two different positions), while a 28-base deletion in mecI was
      found in one strain. In contrast, no mutation was detected in these gene
      sequences of MRSE strains.

PMID- 9517963
TI  - Comparative in vitro activities and postantibiotic effects of the oxazolidinone
      compounds eperezolid (PNU-100592) and linezolid (PNU-100766) versus vancomycin
      against Staphylococcus aureus, coagulase-negative staphylococci, Enterococcus
      faecalis, and Enterococcus faecium.
AB  - The activities of the oxazolidinone antibacterial agents eperezolid (PNU-100592)
      and linezolid (PNU-100766) were compared with that of vancomycin against clinical
      isolates of methicillin-susceptible and -resistant Staphylococcus aureus (n =
      200), coagulase-negative staphylococci (n = 100), and vancomycin-susceptible and 
      resistant Enterococcus faecalis and Enterococcus faecium (n = 50). Eperezolid and
      linezolid demonstrated good in vitro inhibitory activity, regardless of
      methicillin susceptibility for staphylococci (MIC at which 90% of the isolates
      are inhibited [MIC90] range, 1 to 4 microg/ml) or vancomycin susceptibility for
      enterococci (MIC90 range, 1 to 4 microg/ml). In time-kill studies, eperezolid and
      linezolid were bacteriostatic in action. A postantibiotic effect of 0.8+/-0.5 h
      was demonstrated for both eperezolid and linezolid against S. aureus, S.
      epidermidis, E. faecalis, and E. faecium.

PMID- 9517964
TI  - Morphological effects of miconazole on Helicobacter pylori.

PMID- 9517965
TI  - Selection of fluoroquinolone-resistant methicillin-resistant Staphylococcus
      aureus with ciprofloxacin and trovafloxacin.

PMID- 9517966
TI  - [The current aspects of the clinical picture, diagnosis and therapy of
      inflammatory diseases of the oral cavity, oropharynx and salivary glands].

PMID- 9517967
TI  - [The current status of the care for lymph drainage in malignant head-neck
      tumors].

PMID- 9517968
TI  - [Therapeutic decisions in advanced malignomas of the oropharynx].

PMID- 9517969
TI  - [The use of modern audiological procedures in the fitting of hearing aids].

PMID- 9517970
TI  - [The latest developments in ultrasonic diagnosis. I: New technical developments;
      ultrasonic study of the soft-tissue structures of the neck].

PMID- 9517971
TI  - [The latest developments in ultrasonic diagnosis. II. Sonographic study for
      assessing tumors with possible vascular involvement, of facial soft tissues and
      of the bony structures of the face].

PMID- 9517972
TI  - [The use of botulinum toxin in otorhinolaryngology--experiences and outlook].

PMID- 9517973
TI  - [Central nervous system evoked potentials in peripheral antidromic stimulation of
      the n. facialis].

PMID- 9517974
TI  - [Septoplasty].

PMID- 9517975
TI  - [Surgery of rhinophyma and osteotomies--new developments in rhinoplastic
      surgery].

PMID- 9517976
TI  - [Reconstruction of the pronounced saddle nose].

PMID- 9517977
TI  - [The closure of septal defects].

PMID- 9517978
TI  - [Surgery of the tip of the nose].

PMID- 9517979
TI  - [Principles of cleft nose correction].
AB  - BACKGROUND: Cleft lips are very common malformation and all patients present a
      typical feature of the nose. The correction of a cleft nose is the most important
      step in secondary rehabilitation of CLP patients. Adequate correction of the
      septum is a must for the functional as well as the aesthetic result. In many
      cases it will become necessary to take out the whole septum, to build up a
      straight septum plate and to replant it. To keep the replanted septum in the
      midline it is necessary to bring the dislocated anterior nasal spine into the
      correct position. After closure of the lip, the deformity of the nasal tip and
      the nostrils preserve the stigma of the CLP patient. To achieve symmetry of the
      cartilagenous structures and the deformed soft tissue, a triple swing flap
      technique is recommended, which we have up to now used in 261 patients.

PMID- 9517980
TI  - [The development and present-day status of plastic and reconstructive surgery in
      the ENT field in Germany].

PMID- 9517981
TI  - [The prospects for operations in inner-ear hearing disorder].

PMID- 9517982
TI  - [The latest developments in intraoperative 3D navigation in the ENT area].

PMID- 9517983
TI  - [The current status of broncho-esophagoscopy in otorhinolaryngology].
AB  - Most bronchoscopies and esophagoscopies are currently performed with flexible
      instruments by the respective specialist. Thus the field of bronchoesophagology
      is in danger of being fragmented; neither the pneumologist nor the
      gastroenterologist have the complete overview of the upper respiratory and
      digestive tract. This review shows that number of pathologic conditions in the
      ENT area and the mediastinum involve the upper respiratory as well as the
      digestive tract, and thus underscore the need for combined tracheobronchial and
      esophageal endoscopy. Mastering of rigid and flexible endoscopy is mandatory to
      be efficient in diagnostic and therapeutic broncho-esophagoscopy. The ENT
      specialist is in the best position to maintain an overview of this whole field.
      New developments in broncho-esophagoscopy are presented and discussed in terms of
      cost effectiveness.

PMID- 9517984
TI  - [New developments in endoscopy].
AB  - Beside the developments of new imaging modalities in endoscopy, efforts have been
      made to improve therapeutical possibilities of endoscopic interventions. In
      addition to the improvement or even development of new instruments for flexible
      and rigid endoscopy, the potentials of the new technique of argon-plasma
      coagulation in ENT are only hardly discovered. This innovative method is based on
      high-frequency (HF) electric current for non contact tissue coagulation via
      ionized argon gas. It leads to a homogeneous coagulation and desiccation zone
      with a limited and controlled tissue penetration. In addition a multifunctional
      instrument is presented for the resection of tumors in the upper aero-digestive
      tract which is able to cut and coagulate tissue on an HF basis and is provided
      with a channel for suction and irrigation. Additional instruments are offered for
      the laser surgical resection of tumors through the microlaryngoscope. These
      instruments are equipped with a cable connection for HF current and are helpful
      for controlling and managing large bleeding tumor masses. The increasing
      significance of the flexible endoscopy in ENT surgery is being taken into
      consideration by the development of additional instruments to remove all kind of
      foreign bodies in the esophagus or tracheo bronchial system. Through the creation
      of new materials it is also possible to perform an endoscopic dilatation of
      esophageal or hypopharyngeal stenoses with a reduced risk of perforations.

PMID- 9517985
TI  - Neuroimaging of the AIDS dementia complex.

PMID- 9517986
TI  - HIV p17 enhances lymphocyte proliferation and HIV-1 replication after binding to
      a human serum factor.
AB  - OBJECTIVE: To analyse the role of recombinant HIV-1 protein p17 in the modulation
      of cell activity. METHODS: Peripheral blood mononuclear cells (PBMC) obtained
      from healthy donors were cultured in the presence or absence of p17 with mitogens
      such as phytohaemagglutinin or interleukin-2 and their response assayed by cell
      proliferation. Cross-linking experiments were employed to investigate the
      presence of a binding between p17 and factor(s) present in human serum. An
      immunoenzymatic assay for p24 antigen detection was used to analyse the effect of
      the addition of exogenous p17 to cultures of PBMC infected with HIV-1 in vitro.
      RESULTS: Purified recombinant p17 protein at a concentration of 0.25 microg/ml
      significantly increased the proliferation of preactivated PBMC obtained from
      healthy donors. This effect was obtained by binding p17 to factor(s) present in
      human serum and observed on both CD4+ and CD8+ T cells. Recombinant p17 also
      induced an increased rate of HIV-1 replication, probably due to enhanced T-cell
      proliferation. The activity of p17 protein was inhibited by anti-p17 antibodies
      generated by injecting recombinant p17 in rabbits, but not by human antibodies
      generated during the natural course of HIV infection. CONCLUSION:
      Characterization of the human factor(s) and identification of the interacting p17
      epitope(s) will improve our understanding of the mechanisms used by HIV to
      efficiently replicate in our organisms.

PMID- 9517987
TI  - Hematopoietic transcription factor GATA-2 activates transcription from HIV-1 long
      terminal repeat.
AB  - OBJECTIVES: To study the role of the hematopoietic transcription factor GATA-2 in
      long terminal repeat (LTR)-directed transcriptional activation of HIV-1 in
      hematopoietic progenitor cells, and to investigate possible GATA-2 binding sites
      in HIV-1 LTR. DESIGN AND METHODS: Wild-type HIV-1 LTR, or mutants, ligated to a
      luciferase reporter gene with or without a GATA-2 expression vector, were
      transfected into COS cells, and standardized luciferase activity was examined.
      The binding activity of GATA-2 to these sites was examined by electrophoretic
      mobility shift assay. These wild-type or mutant reporter genes were also
      transfected into the murine hematopoietic progenitor cells, BAF3, in which GATA-2
      was the predominantly expressed transcription factor of the GATA family, to assay
      LTR-directed transcription in intact hematopoietic machinery. Using a Tat
      expression plasmid for cotransfection, the influence of Tat protein on GATA-2
      induced transactivation was determined. RESULTS: In COS cells, LTR-dependent
      transactivation was highly enhanced by the coexpression of GATA-2. Experiments
      with mutant LTR suggested the presence of multiple GATA-2 binding sites, of which
      the major sites were identified. Cotransfection of Tat with GATA-2 indicated that
      GATA-2 and Tat synergistically enhanced the transcriptional activity.
      Transfection experiments in BAF3 cells showed that the disruption of these GATA
      sites diminished LTR-driven activity to 40% of the wild-type. CONCLUSIONS: GATA-2
      may be a key host cell regulator of HIV-1 expression in hematopoietic stem cells.
      Manipulating this transactivation may represent a valuable approach to
      controlling virus production in infected hematopoietic progenitors. To elucidate
      the possible interaction between GATA-2 and Tat protein in vivo might give new
      insights to the mechanism of impaired hematopoiesis in AIDS patients.

PMID- 9517988
TI  - Monocyte-derived dendritic cells and monocytes migrate to HIV-Tat RGD and basic
      peptides.
AB  - OBJECTIVE AND DESIGN: Extracellular Tat released from HIV-1-infected cells is a
      mitogenic and motogenic factor for endothelial and Kaposi's sarcoma (KS)-derived
      cells and is angiogenic in vivo. Here we show for the first time that Tat induces
      migration of human dendritic cells in a concentration-dependent manner and that
      the Arg-Gly-Asp (RGD) and basic Tat peptides contribute to dendritic and monocyte
      cell migration. In vivo, Tat stimulates invasion of macrophages into a matrigel
      sponge. METHODS: Monocyte and dendritic cell chemotaxis was assessed using the
      Boyden chamber assay. RESULTS: Tat induced migration of monocyte-derived
      dendritic cells at the same levels as the N-formyl-Met-Leu-Phe peptide, and of
      monocytes at levels comparable to RANTES. Peptide mapping of the chemotactic
      activity of Tat showed that the RGD domain, which has been shown to support
      integrin-mediated cell migration, and the basic domain which binds and activates
      the tyrosine kinase receptor KDR on endothelial cells, both had activity.
      Antibody-blocking experiments indicate that responses to the RGD domain was
      inhibited by beta1 and alpha vbeta3 integrin blocking antibodies. Combination of
      the Tat RGD and basic peptides did not show additive effects; however, Tat co
      operated with macrophage-chemotactic protein or RANTES in inducing monocyte
      migration. CONCLUSIONS: Our results show that Tat can act as a chemoattractant
      for dendritic cells, and that both the RGD and basic domains are involved in this
      response. These same domains attract monocytes. The alpha vbeta3 and beta1
      integrins are equally involved in Tat-induced monocyte migration, while the alpha
      vbeta3 integrin largely mediates the dendritic cell response to Tat.

PMID- 9517989
TI  - A randomized, placebo-controlled trial of the safety and efficacy of oral
      ganciclovir for prophylaxis of cytomegalovirus disease in HIV-infected
      individuals. Terry Beirn Community Programs for Clinical Research on AIDS.
AB  - OBJECTIVE: Evaluate safety and efficacy of oral ganciclovir (GCV) for preventing
      cytomegalovirus (CMV) disease in HIV-infected persons at high risk for CMV
      disease. DESIGN: Double-blind, placebo-controlled, randomized clinical trial in
      primary care clinics and private practice offices specializing in the care of
      people with HIV. Interventions were oral GCV (1000 mg three times/day) or
      placebo. Protocol amendment allowed switch to open-label oral GCV. Main outcome
      measures were confirmed CMV retinal or gastrointestinal mucosal disease, and
      death. The study enrolled 994 people co-infected with CMV and HIV, with at least
      one CD4 count recorded < 100 x 10(6) cells/l. RESULTS: At study completion (15
      months median follow-up), CMV event rates in the oral GCV and control groups were
      13.1 and 14.6 per 100 person years, respectively, a hazard ratio (HR) of 0.92
      [95% confidence interval (CI), 0.65-1.27; P = 0.6]. At protocol amendment event
      rates were 12.7 and 15.0, respectively (HR, 0.85; 95% CI, 0.56-1.30; P = 0.45).
      At study completion, event rates for death were 26.6 and 32.0 (HR, 0.84; P =
      0.09), and at protocol amendment were 18.9 and 19.6 (HR, 0.95; P = 0.78),
      respectively. At protocol amendment for the CMV endpoint, the oral GCV treatment
      effect was associated with baseline use of didanosine (ddI). For patients taking
      ddI at randomization, HR was 7.48 (P = 0.02). For patients not taking ddI, HR was
      0.62 (P = 0.04). These HR were statistically different (P = 0.0006). CONCLUSIONS:
      In our study, 3 g/day oral GCV did not significantly reduce CMV disease
      incidence, but there was a suggestion of a death-rate reduction. Furthermore,
      results suggest that oral GVC decreased risk of CMV disease in patients not
      prescribed ddI, and increased risk in those prescribed ddI. For the CMV endpoint,
      our study differs markedly from the only similar study, although for the death
      endpoint, a combined analysis of studies indicated significant reduction in death
      rate.

PMID- 9517990
TI  - Antiviral effect of double and triple drug combinations amongst HIV-infected
      adults: lessons from the implementation of viral load-driven antiretroviral
      therapy.
AB  - OBJECTIVE: To study the antiviral effect and predictors of response to two- and
      three-drug regimens amongst antiretroviral-naive individuals using an intent-to
      treat analysis. MAIN OUTCOME MEASURE: Suppression of plasma viral load to < 500
      copies/ml. PATIENTS: A total of 420 (264 double drug, 156 triple drug)
      individuals in a province-wide treatment programme were studied. RESULTS: A
      decrease in plasma viral load to < 500 copies/ml was documented in 197 (47%)
      subjects. This was independently associated with a lower baseline plasma viral
      load (odds ratio, 3.67; 95% confidence interval, 2.13-6.30) and initiation onto a
      three-drug regimen (odds ratio, 3.86; 95% confidence interval, 2.24-6.66). Median
      plasma viral load failed to reach < 500 copies/ml and in fact rebounded in the
      two-drug group. In contrast, 91 (58%) subjects receiving three drugs reached <
      500 copies/ml during the study period. CONCLUSION: These results support the use
      of powerful triple drug regimens as initial therapy in HIV-infected individuals.

PMID- 9517991
TI  - Molecular epidemiological analysis of HIV in sexual networks in Uganda.
AB  - OBJECTIVE: To investigate the suitability of HIV sequence analysis, based on the
      p17 region of the gag gene, to characterize the sexual networks in and around a
      trading town in south-west Uganda. METHODS: Blood samples were obtained from 54
      HIV-seropositive members of three distinct sexual networks and phylogenetic
      analysis carried out on proviral DNA sequences obtained from the p17 region of
      gag from 53 individuals. RESULTS: Despite documented evidence of very little
      sexual mixing between residents of the trading town, fishing village and
      surrounding rural area, there was no evidence of clustering of sequences
      associated with place of residence. More strikingly, known sexual partners failed
      to show significantly related sequences, and the two pairs of sequences that did
      show significant similarity came from individuals who had no known social or
      sexual contact. CONCLUSIONS: Sequence analyses such as those described here have
      proved effective in confirming or identifying epidemiological links not only
      following single transmission events but also within risk groups. However, the
      results from Uganda contrast markedly with those from Europe and the United
      States. The length of time that the community has been infected, the number of
      occasions when the virus has been introduced and the high degree of partner
      change may contribute to the lack of supportive evidence for sociological studies
      of sexual networks in Uganda.

PMID- 9517992
TI  - Genetic subtypes of HIV-1 in the Philippines.
AB  - OBJECTIVES: To determine the genetic variability of HIV-1 amongst infected
      Filipinos and to analyze phylogenetic relationships, temporal introductions and
      transmission dynamics of identified variants. METHODS: Polymerase chain reaction
      amplification and direct sequencing of a 204 base-pair fragment of the env C2-V3
      region from uncultured peripheral blood mononuclear cells obtained from 51 HIV-1
      positive Filipinos infected from 1987 to mid-1996. Evolutionary distance and
      phylogenetic relationships among the DNA sequences were estimated. RESULTS: The
      51 Philippine strains were classified into five env V3 subtypes, namely subtype B
      (n = 37), subtype E (n = 8), subtype A (n = 3), subtype C (n = 2) and subtype D
      (n = 1). The overall env nucleotide divergence ranged from 11.7 to 32.2%. The
      nucleotide variation appeared to be random and no temporal ordering was observed.
      The variation of the sequences at the tip of the V3 loop was very broad. Subtypes
      B and C isolates did not show close genetic relationship to other Asian variants.
      Only three of the subtype E strains had close affinity to known Asian sequences.
      The majority (94%) of the subjects acquired the infection by sexual transmission.
      About two-thirds were presumably infected outside the Philippines, whereas the
      remaining were infected indigenously. Information was limited to allow
      segregation of the identified subtypes by mode of transmission or risk groups.
      CONCLUSION: Our findings demonstrate the presence of multiple genetic subtypes of
      HIV-1 in the Philippines. The apparent geographic range of previously reported
      genotypes in South and South-east Asia was extended and has obvious implications
      for env-based antiviral interventions.

PMID- 9517993
TI  - Impact of zidovudine use on risk and risk factors for perinatal transmission of
      HIV. Perinatal AIDS Collaborative Transmission Studies.
AB  - OBJECTIVES: To evaluate the impact of perinatal zidovudine use on the risk of
      perinatal transmission of HIV and to determine risk factors for transmission
      among women using perinatal zidovudine. DESIGN: Prospective cohort study of 1533
      children born to HIV-infected women between 1985 and 1995 in four US cities.
      METHODS: The association of potential risk factors with perinatal HIV
      transmission was assessed with univariate and multivariate statistics. RESULTS:
      The overall transmission risk was 18% [95% confidence interval (CI), 16-21].
      Factors associated with transmission included membrane rupture > 4 h before
      delivery [relative risk (RR), 2.1; 95% CI, 1.6-2.7], gestational age < 37 weeks
      (RR, 1.8; 95% CI, 1.4-2.2), maternal CD4+ lymphocyte count < 500 x 10(6) cells/l
      (RR, 1.7; 95% CI, 1.3-2.2), birthweight < 2500 g (RR, 1.7; 95% CI, 1.3-2.1), and
      antenatal and neonatal zidovudine use (RR, 0.6; 95% CI, 0.4-0.9). For infants
      exposed to zidovudine antenatally and neonatally, the transmission risk was 13%
      overall but was significantly lower following shorter duration of membrane
      rupture (7%) and term delivery (9%). The transmission risk declined from 22%
      before 1992 to 11% in 1995 (P < 0.001) in association with increasing zidovudine
      use and changes in other risk factors. CONCLUSIONS: Perinatal HIV transmission
      risk has declined with increasing perinatal zidovudine use and changes in other
      factors. Further reduction in transmission for women taking zidovudine may be
      possible by reducing the incidence of other potentially modifiable risk factors,
      such as long duration of membrane rupture and prematurity.

PMID- 9517994
TI  - Profile of central nervous system pathology in patients with AIDS: an autopsy
      study from India.
AB  - OBJECTIVE: To study the spectrum of neuropathological brain lesions in HIV/AIDS
      cases. DESIGN: Retrospective autopsy study between 1988 and mid-1996 at a
      tertiary level public hospital. METHODS: Eighty-five adult brains, with at least
      21 sections from each, were examined using routine and special stains. RESULTS:
      Risk factors in 64 men (75%) and 21 women (25%) included heterosexual contact
      with multiple sexual partners (83 cases, 98%), homosexual behaviour (one case,
      1%) and blood transfusion (one case, 1%). Central nervous system (CNS) lesions
      were observed in 67 cases (79%). Opportunistic infections were present in 33
      cases (39%), which included toxoplasmosis (11 cases, 13%), tuberculosis (10
      cases, 12%), cryptococcosis (seven cases, 8%), and cytomegalovirus infection (six
      cases, 7%). Multifocal myelin loss was observed in 18 cases (21%), microglial
      nodules in 15 cases (18%), and angiocentric pallor in five cases (6%).
      Infarcts/haemorrhages were present in 13 cases (15%), choroid plexitis in 21
      cases (25%), lymphocytic meningitis without opportunistic infection in 21 cases
      (25%), and calcification in four cases (5%). A dual infectious pathology was
      observed in one case (1%). Multinucleated giant cells and primary CNS lymphoma
      were not found in any of our cases. CONCLUSIONS: Patient profile and risk factors
      for AIDS in India differ from those reported in industrialized countries.
      Although not reported from India in the pre-AIDS era, toxoplasmosis was the most
      frequently observed CNS opportunistic infection in our study. CNS tuberculosis is
      frequently observed in Indian AIDS cases compared with reports from
      industrialized countries where its occurrence is uncommon. Death due to systemic
      opportunistic infections may punctuate the course of HIV encephalitis and prevent
      its full-blown morphological expression.

PMID- 9517995
TI  - Age- and sex-specific HIV-1 prevalence in the urban community setting of Addis
      Ababa, Ethiopia.
AB  - OBJECTIVE: To estimate the age and sex-specific prevalence of HIV infection in
      the population of Addis Ababa, Ethiopia. DESIGN: Two-stage cluster sampling of
      the population aged 0-49 years of Addis Ababa, using kebeles (urban dwelling
      associations) as clusters. METHODS: The sera used for this study were collected
      in an earlier study (1994) on the rate of acquisition of antibodies against
      measles, rubella, and hepatitis B. After separate approvals were obtained from
      the institutional ethics committees, sera were tested by enzyme-linked
      immunosorbent assay confirmed by Western blot. Age- and sex-specific HIV
      prevalence rates were estimated. The prevalence of HIV in men and women over 15
      years of age was compared by calculating age-standardized HIV prevalence, using
      the age distribution of the census population as the standard. A time-dependent
      catalytic model was used to obtain crude estimates of HIV incidence from age
      prevalence data. RESULTS: A total of 3853 sera were available for analysis. The
      prevalence of HIV in adults was 6.0% [95% confidence interval (CI), 4.5-7.4%] for
      men and 6.9% (95% CI, 5.3-8.5%) for women, with peak prevalence in the 25-29 year
      age group of 16.3 and 11.8%, respectively. After standardization for age using
      the direct method, the HIV prevalence ratio comparing adult men with women was
      0.97:1 (95% CI, 0.70:1 - 1.35:1). Three children aged less than 5 years were HIV
      positive. The prevalence of HIV among adults ranged from 0-21.3% in different
      clusters, indicating the heterogeneity of the spread of HIV in the city. HIV
      prevalence estimates among the antenatal clinic patients of Addis Ababa in 1996
      far exceeded the estimates obtained during the community survey, particularly in
      the youngest age group (15-24 years). Estimates of HIV incidence (per susceptible
      person per annum) for the age group 16-22 years ranged from 1.3-2.25% for men and
      from 2.1-2.4% for women. CONCLUSION: By 1994, a substantial proportion of the
      adult population of Addis Ababa was infected with HIV. Promotion of behavioural
      changes and the control of sexually transmitted diseases should be strongly
      supported to limit the spread of the HIV epidemic in Ethiopia.

PMID- 9517996
TI  - Longer survival after HIV infection for injecting drug users than for homosexual
      men?

PMID- 9517997
TI  - Ritonavir pharmacokinetics alone and in combination with saquinavir in HIV
      infected patients.

PMID- 9517998
TI  - Long-term testosterone therapy in HIV-positive men: side-effects and maintenance
      of clinical benefit.

PMID- 9517999
TI  - Indinavir-related alopecia.

PMID- 9518001
TI  - HIV infection among women of reproductive age.

PMID- 9518000
TI  - A subunit vaccine consisting of gp130 oligomers but not of gp130 monomers
      protects rhesus macaques against productive infection with SIVmac32H.

PMID- 9518002
TI  - Maternal serum lactoferrin and vertical transmission of HIV.

PMID- 9518003
TI  - Seminal viral load.

PMID- 9518005
TI  - Improved survival by home total parenteral nutrition in AIDS patients: follow-up
      of a controlled randomized prospective trial.

PMID- 9518004
TI  - Effects of thalidomide therapy in symptomatic simian immunodeficiency virus
      infected cynomolgus monkeys.

PMID- 9518006
TI  - In bacterial reaction centers, a key residue suppresses mutational blockage of
      two different proton transfer steps.
AB  - In reaction centers of Rhodobacter (Rb.) capsulatus, the M43Asn --> Asp
      substitution is capable of restoring rapid rates for delivery of the second
      proton to QB in a mutant that lacks L212Glu. Flash-induced absorbance
      spectroscopy was used to show a nearly native rate for transfer of the second
      proton to QB (approximately 700 s-1) in the L212Gln+M43Asp double-mutant reaction
      center; this rate was shown to decrease more than 1000-fold in the
      photoincompetent L212Glu --> Gln mutant [Miksovska, J., Kalman, L., Maroti, P.,
      Schiffer, M., Sebban, P., and Hanson, D.K. (1997) Biochemistry 36, 12216-12226].
      In Rb. sphaeroides, the equivalent M44Asn --> Asp mutation was reported to
      restore the rate of transfer of the first proton to a wild-type level when it is
      added to the L213Asp --> Asn photoincompetent mutant [Rongey, S.H., Paddock,
      M.L., Feher, G., and Okamura, M.Y. (1993) Proc. Natl. Acad. Sci. U.S.A. 90, 1325
      1329]. It is remarkable that the same second-site mutation can compensate for
      both of these mutations which severely impair reaction center function by
      blocking two different proton-transfer reactions. We suggest that residue M43Asp
      is situated in a key position which can link pathways for delivery of both the
      first and second protons (involving structured water molecules) to QB.

PMID- 9518007
TI  - Purification and in vitro reconstitution of the essential protein components of
      an aromatic polyketide synthase.
AB  - A minimal set of proteins which catalyze the synthesis of aromatic polketides
      from malonyl CoA has been purified and partially characterized. Plasmid-encoded
      actinorhodin (act) ketosynthase/chain-length factor (KS/CLF) complex was purified
      from Streptomyces coelicolor CH999/pSEK38, and assayed with purified aromatic PKS
      holo-ACPs which were overproduced and purified from Escherichia coli and
      phosphopantetheinylated in vitro using purified E. coli holo-ACP synthase. When
      highly purified preparations of KS/CLF, and holo-ACP failed to catalyze
      polyketide biosynthesis, a fourth protein was sought and purified from the S.
      coelicolor CH999 host on the basis of its ability to complement KS, CLF, and holo
      ACP in polyketide synthesis. N-terminal sequencing identified this protein as the
      fatty acid synthase (fabD) malonyl CoA:ACP transacylase (MAT), recruited from
      primary metabolism. A alpha2/beta2 structure was shown for the act KS/CLF
      complex, and three malonyl-enzyme biosynthetic intermediates were identified,
      defining an escorted path followed by malonyl groups en route from CoA to
      polyketide.

PMID- 9518008
TI  - Pneumococcal vaccination and HIV infection.

PMID- 9518009
TI  - Clinical predictors of azole resistance, outcome and survival from oesophageal
      candidiasis in AIDS patients.
AB  - A retrospective review of AIDS-related oesophageal candidiasis was undertaken to
      identify clinical features helpful in predicting response to azole therapy and
      patient survival. Patients who had received daily azole prophylaxis against
      candidiasis were significantly less likely to respond to azole therapy than those
      who had not (P < 0.001). Patients who had lost > 5% of their body weight in the 2
      months before oesophageal candidiasis were less likely to respond to azoles than
      the others (P < 0.001). Amongst those who had not received daily azoles, patients
      with a CD4+ cell count < 25/mm3 were less likely to respond to azole treatment (P
      = 0.05). The median survival beyond oesophageal candidiasis was 18 months.
      Survival from oesophageal candidiasis was significantly poorer for patients who
      did not respond to azole therapy but AIDS survival did not differ between azole
      responders and non-responders. Non-responders who had been taking daily azole
      prophylaxis had the poorest survival (median = 4 months).

PMID- 9518011
TI  - A lasting public health response to an outbreak of HIV infection in a Scottish
      prison?
AB  - Between April and June 1993, 8 cases of acute clinical hepatitis B infection and
      2 seroconversions to HIV infection were detected among drug injecting inmates of
      HM Prison Glenochil in Scotland. To prevent the further spread of infection, an
      initiative which involved counselling and voluntary attributable HIV testing was
      conducted over a 10-day period commencing at the end of June. A team of 18
      counsellors and phlebotomists was brought together rapidly as part of a unique
      organizational exercise in the field of public health. Fourteen cases of HIV
      infection were identified of which 13 were almost certainly infected in
      Glenochil. Following the exercise, a range of harm reduction measures for
      injecting prisoners was introduced; these included the availability of hepatitis
      B vaccine, provision of bleach tablets which could be used to clean injecting
      equipment, a methadone detoxification programme, increased training for prison
      officers and improved access to drug and harm minimization counselling for
      inmates. By mid-1996 all these measures had been sustained and several could be
      found in many other prisons throughout Scotland. Follow-up investigations showed
      no evidence of epidemic spread of HIV during the 12 months after the initiative.
      While the frequency of injecting and needle/syringe sharing may have decreased
      over the last 3 years, these activities are still being reported and it is highly
      likely that transmissions of bloodborne infections, in particular hepatitis C,
      continue to occur. The surveillance and prevention of infections associated with
      injecting drug use in the prison setting remain a high public health priority.

PMID- 9518010
TI  - Detection of male genital infection with Chlamydia trachomatis and Neisseria
      gonorrhoeae using an automated multiplex PCR system (Cobas Amplicor).
AB  - We evaluated Cobas Amplicor, a highly automated polymerase chain reaction (PCR)
      system, to test first-void urine (FVU) and urethral swab specimens for Chlamydia
      trachomatis and Neisseria gonorrhoeae in men attending a sexually transmitted
      infection (STI) clinic. Results were compared against an in-house radioimmune dot
      blot (DB) test for C. trachomatis and selective culture for N. gonorrhoeae. Three
      hundred and ninety sets of specimens were obtained from 378 consecutive new and
      returned-new patients. Gonorrhoea prevalence was 9.49%, with no significant
      difference in sensitivity or specificity between culture and PCR. Chlamydia
      prevalence was 15.4%, with sensitivities of: DB 55%, PCR of FVU 86.7%, urethral
      swab PCR 90%. The specificity of PCR on FVU and urethral swabs was 100%. We have
      shown that Cobas Amplicor PCR is highly sensitive and specific in the diagnosis
      of chlamydia and gonorrhoea in men attending an STI clinic. Further economic and
      scientific studies are needed to determine the cost-effectiveness of this
      technique for screening in primary care settings.

PMID- 9518013
TI  - Anal cytological abnormalities in HIV-infected homosexual men.
AB  - This study aimed to examine the prevalence of anal cytological abnormalities in
      groups of HIV-infected and non-infected homosexual men, and to monitor changes
      with time. Dyskaryosis suggestive of anal intraepithelial neoplasia (AIN) was
      noted in 24 (30%) of the 80 satisfactory anal smears from 66 HIV-seropositive
      homosexual men; such changes were found in only 7 (4.7%) of the 149 satisfactory
      smears from 181 HIV-seronegative homosexual men (P < 0.005), and in none of 34
      satisfactory preparations from 51 HIV-seronegative heterosexual men. In the
      follow-up of 20 HIV-seropositive men, the severity of the cytological
      abnormalities found in 2 men increased, with the most recent smear showing
      changes suggestive of AIN III; one of these men subsequently developed anal
      cancer. Smears from 4 men showed apparent regression in the degree of
      dyskaryosis. Although the numbers of patients studied were small, there appeared
      to be a trend towards a more severe degree of dyskaryosis in those men with
      increasing immunodeficiency. There was no significant difference in the detection
      of human papillomavirus types 6b, 11, 16 and 18 between HIV-infected and non
      infected men.

PMID- 9518012
TI  - Seroprevalence of four sexually transmitted diseases in a semi-urban population
      of Gabon.
AB  - Using the cluster-sampling method, the authors estimated the seroprevalence of 4
      sexually transmitted diseases (STDs) among the sexually active general population
      in a city of 30,000 inhabitants in the east of Gabon. The seroprevalences were 2%
      for HIV-1, 13.8% for hepatitis B, 8.6% for Treponema pallidum and 59.6% for
      Chlamydia trachomatis. The seroprevalences of hepatitis B and chlamydia were
      stable over time and similar to those registered in other countries of central
      Africa. On the other hand, the seroprevalence of T. pallidum is notably low in
      comparison with these countries and seems to be decreasing. The seroprevalence of
      HIV-1 is also low but has doubled in 8 years in the city. Immigrant women from
      west Africa were a high-risk group for STDs but more generally, cohabiting was a
      risk factor for women.

PMID- 9518014
TI  - Testosterone therapy for clinical symptoms of hypogonadism in eugonadal men with
      AIDS.
AB  - We conducted a small exploratory study to assess whether testosterone therapy is
      an effective treatment for clinical symptoms characteristic of hypogonadism in
      eugonadal men with AIDS. Treatment consisted of 12 weeks of bi-weekly
      intramuscular injections of testosterone cypionate. Twenty-three men enrolled in
      the study; mean age was 37 and 44% were ethnic minorities. All had an AIDS
      diagnosis and the mean CD4 cell count was 150 cells/mm3. All baseline serum
      testosterone levels were within the laboratory reference range and above 500
      ng/dl. Diminished libido was an inclusion criterion, plus each patient had at
      least one additional symptom (low mood, low energy, loss of appetite and/or
      weight). Nineteen men completed the trial and a majority of patients responded
      with regard to libido (89%), mood (67%), energy (71%), and appetite (67%) as
      rated by the Clinical Global Impressions Scale. With the exception of appetite,
      self and clinician rated measures showed significant improvement in all symptom
      domains. Among the 14 study completers with significant weight loss, the average
      weight gain was 2.3 kg, with a 1.8 kg increase in body cell mass and no change in
      body fat. These results suggest that testosterone is as effective in treating
      these symptoms in eugonadal men with AIDS as we have found in our research with
      hypogonadal HIV+men.

PMID- 9518015
TI  - Low HIV and high STD among commercial sex workers in a brothel in Bangladesh:
      scope for prevention of larger epidemic.
AB  - The present study documents the first systematic assessment of a brothel in
      Bangladesh in terms of sexually transmitted disease (STD) and human
      immunodeficiency virus (HIV). A cross sectional study was undertaken on brothel
      based commercial sex workers (CSWs) selected systematic random sampling to assess
      the prevalence of STDs and HIV among CSWs in a brothel setting. Two hundred and
      ninety-six CSWs were selected from a brothel with a population of 593 women.
      Following informed consent, endocervical and blood samples were obtained for the
      diagnosis of genital chlamydia, gonorrhoea, HIV and syphilis respectively. In
      addition, another 170 consecutive blood samples were collected from the total CSW
      population for HIV tests. All blood samples for HIV testing were made anonymous
      by removing patient identifiers before testing. Endocervical specimens were
      tested by polymerase chain reaction (PCR) for the diagnosis of genital chlamydia
      and gonorrhoea. Syphilis and HIV infections were diagnosed by serology. One
      hundred and sixty-nine (57.1%) of the women were Treponema pallidum
      haemagglutination (TPHA)-positive, 20 (6.8%) of the women were Venereal Disease
      Research Laboratory (VDRL)-positive at a greater than 1:8 dilution. Eighty-two
      (28%) of the women were found to be infected either by gonorrhoea or chlamydia.
      No HIV antibody was found in any of the 466 blood samples. A high prevalence of
      STDs and low prevalence of HIV in the CSWs in Bangladesh suggest potential for
      the rapid spread of HIV once it is introduced in this high-risk population. The
      opportunity to control STD and HIV infection in this population should not be
      missed, in order to prevent a large epidemic in the future.

PMID- 9518017
TI  - Sexual exposure to HIV infection: is there a role for emergency prophylaxis?

PMID- 9518016
TI  - An audit of emergency contraception: a look at patient characteristics and the
      effects of a consultation proforma.
AB  - The aim of this study was to examine the characteristics of patients requesting
      emergency postcoital contraception at a genitourinary medicine (GUM) clinic. We
      also compared the quality of information obtained during the consultation, before
      and after a proforma was introduced. A retrospective review of all clinical notes
      of patients who attended for postcoital contraception between January and
      December 1994 and April to June 1995 was performed. Eighty-three per cent of
      patients were aged 17-29 years, 68.8% were in relationship, 41.3% were not using
      regular contraception, 33.8% accepted a sexual health screen and of these, 14.8%
      had a concurrent sexually transmitted disease (STD). The introduction of a
      consultation proforma significantly improved certain areas of the consultation.
      The results suggest that sexual health screens should be encouraged in women
      attending GUM clinics for postcoital contraception and that the use of a proforma
      improves the quality of information obtained.

PMID- 9518018
TI  - Indinavir-associated hepatitis in patients with advanced HIV infection.

PMID- 9518019
TI  - Larva migrans as a cause of fever in an HIV-positive man.

PMID- 9518020
TI  - Mycobacterium avium-intracellulare complex causing penile ulceration in an
      immunocompetent man.

PMID- 9518021
TI  - Knowledge and attitudes about HIV/AIDS among health care professionals serving
      Tibetan refugees in northern India.

PMID- 9518022
TI  - Cyclospora cayetanensis and HIV-related diarrhoea.

PMID- 9518023
TI  - Gonorrhoea and chlamydia coinfection in gay men.

PMID- 9518024
TI  - Donovanosis: treatment with azithromycin.

PMID- 9518025
TI  - Outcomes in genitourinary medicine: whose priority?
AB  - The primary role of genitourinary medicine (GUM) services in the UK is the
      treatment and control of sexually transmitted diseases (STDs). The origins of the
      service lie in its public health function, yet measuring outcomes locally and
      nationally is not straightforward. Difficulties arise from the complex
      interactions between sexual behaviour, the biology of STDs and the role of
      clinical services; from the potential consequences of the National Health Service
      (NHS) internal market on national STD control; and from the limitations of
      information and surveillance systems. This paper considers each of these areas in
      turn and concludes with some proposals for measuring GUM outcomes locally and
      nationally which might potentially satisfy the concerns of commissioners and
      providers.

PMID- 9518026
TI  - Orientation tuning curves: empirical description and estimation of parameters.
AB  - This paper compares the ability of some simple model functions to describe
      orientation tuning curves obtained in extracellular single-unit recordings from
      area 17 of the cat visual cortex. It also investigates the relationships between
      three methods currently used to estimate preferred orientation from tuning curve
      data: (a) least-squares curve fitting, (b) the vector sum method and (c) the
      Fourier transform method (Worgotter and Eysel 1987). The results show that the
      best fitting model function for single-unit orientation tuning curves is a von
      Mises circular function with a variable degree of skewness. However, other
      functions, such as a wrapped Gaussian, fit the data nearly as well. A cosine
      function provides a poor description of tuning curves in almost all instances. It
      is demonstrated that the vector sum and Fourier methods of determining preferred
      orientation are equivalent, and identical to calculating a least-square fit of a
      cosine function to the data. Least-squares fitting of a better model function,
      such as a von Mises function or a wrapped Gaussian, is therefore likely to be a
      better method for estimating preferred orientation. Monte-Carlo simulations
      confirmed this, although for broad orientation tuning curves sampled at 45 degree
      intervals, as is typical in optical recording experiments, all the methods gave
      similarly accurate estimates of preferred orientation. The sampling interval, the
      estimated error in the response measurements and the probable shape of the
      underlying response function all need to be taken into account in deciding on the
      best method of estimating referred orientation from physiological measurements of
      orientation tuning data.

PMID- 9518027
TI  - [Alcohol withdrawal syndrome: ancient but still thankless].

PMID- 9518029
TI  - [Analysis of experience in an integrated program of hospital rheumatological
      service and primary care].
AB  - BACKGROUND: In order to improve the health quality at the Primary care level, the
      Catalonian Health Authority (Servei Catala de la Salut) has begun a reform of the
      medical and surgical specialties. In this reform process the Hospital del Mar,
      Barcelona, Spain, has taken part in the incorporation of several medical and
      surgical hospital specialists to primary care within its influence area. In this
      study, we describe the results of the collaboration between Hospital health care
      and Primary care on rheumatic complaints during one year. METHODS: We carried out
      a descriptive study of some clinical and epidemiological variables of the
      population visited during one year (1995), at the Primary care level by the
      Rheumatologist. Our area has a population of 90,612 people, and its located in
      Barcelona City, Ciutat Vella Variables of study were collected during the period
      of time between January and December 1995. The following variables were recorded:
      age, gender, referral cause, rheumatologic diagnosis, intra-articular and peri
      articular corticosteroid injections perform, techniques used for the diagnosis of
      rheumatic disease, follow-up level Data were statistically analyzed. RESULTS:
      Visits performed were 2,668 on 1,384 patients. Fifty-two percent were first
      visits, 48% were follow-up visits (Ratio first visits Nolfow-up visits: 0.57).
      Fifty-one percent of the patients were > 65 years old. Unspecific
      polyarthralgias, chronic low back pain, gonalgia and pathology of the shoulder
      were the most frequent complaints (> 50%). Osteoarthritis and soft-tissue
      diseases were the most frequent diagnosis with a percentage of 41% and 30.7%,
      respectively. Connective tissue diseases and spondyloarthropathies had account
      for 3.8% of global diagnosis. X-ray film has been the commonest technique used
      for the diagnosis of rheumatic diseases (80.5%). The waiting list for first visit
      initially has been 5 weeks, and at the end of study it has been 3 weeks. Ten
      percent of patients had been referred to the Hospital. CONCLUSIONS: Collaboration
      between Hospital care rheumatology and Primary care, improves the diagnostic
      quality, as well as it decreases the waiting list and allows the patients'
      control at the most appropriate care level.

PMID- 9518028
TI  - [Study of tuberculosis in Huelva prison].
AB  - OBJECTIVES: Knowing about the rate of tuberculous infection and disease in prison
      population and workers in Huelva prison, and the association of tuberculosis with
      the sociosanitary risk factors. EQUIPMENT AND METHODS: Descriptive research for a
      year in 141 male prisoners at the age of 20 to 52 years old, from the 1sT of
      February in 1994 to the 1sT in 1995. RESULTS: The prevalence on tuberculous
      infection is 46.4% (accumulative incidence); and tuberculous disease 3.5%
      (accumulative incidence 1.4%) on the prisoners and the prevalence on tuberculous
      infection on the prison officers is 18.8% (there wasn't incidence) and the was no
      disease. CONCLUSIONS: It's perceived a high rate of tuberculous disease on the
      prisoners at the expense of people with infection by HIV and drugs addicts by
      parenteral way. The socio-cultural variables affect the tuberculous infection and
      disease tuberculous.

PMID- 9518030
TI  - [Leisure-time physical activity of first-year students in 3 health science
      departments].
AB  - BACKGROUND: Physical inactivity is a well-known risk factor for many chronic
      diseases which have high prevalence in developed countries. The aims of this
      study are to describe leisure-time physical activity levels and to identify
      preferences for its practice among first grade students in three Health Sciences
      Faculties at the University of Barcelona. METHODS: During the year 1994-95, a
      total of 887 first grade students of three Faculties, Pharmacy (n = 573),
      Medicine (n = 222) and Dentistry (n = 92), were interviewed using a recall of
      their leisure time physical activity over last 8 months. Physical activity level
      was classified into four categories: non-active, low, medium and high, based on
      the number of hours per week. Statistical methods consisted in the estimation of
      rates, comparisons using the chi-square test, and computing the odds ratio.
      RESULTS: Women were 75% of students. Fifty per cent of men and 71.5% of women
      referred to be non-active or having low physical activity level (chi 2 = 36.8; DF
      = 3; p < 0.0001), being no evidence of association with current smoking or
      overweight (Body Mass Index > or = 25). Among the rest of students, men's most
      frequently reported activities were football, swimming and tennis, and those of
      women's were swimming, aerobic and tennis. CONCLUSIONS: Physical activity level
      among first grade health sciences university students is poorly exemplary. More
      physical activity promotion is needed, particularly to female students, as an
      important primary preventive measure among this group.

PMID- 9518031
TI  - [Spontaneous splenic rupture: surgical or conservative treatment?].
AB  - A case of Splenic Spontaneous Rupture (SSR) due to Infectious Mononucleosis is
      presented, occurring after a slight clinical course without significative
      abdominal pain. The SSR was recognized by ultrasonography and CT, with free
      intraperitoneal liquid. The evolution was successful with non operative
      management. The Medical literature concerning SSR is comment, enhancing the
      possibility of non operative management of SSR associated to infectious
      mononucleosis.

PMID- 9518033
TI  - [Favorable response to corticoid therapy in a patient with transverse myelitis in
      systemic lupus erythematosus].
AB  - Transverse myelitis is one of the most unusual neurologic complications of
      systemic lupus erythematosus. Its pathogenetic mechanisms are controversial.
      Several therapeutic regimens have been attempted with contradictory results.
      Corticotherapy appears to improve prognosis, although some authors question its
      beneficial effects. The case of a patient with systemic lupus erythematosus and
      transverse myelitis, who presented a favourable clinical course following early
      treatment with high-dose corticoids, is reported.

PMID- 9518032
TI  - [Massive tumorous pulmonary embolism in hepatocarcinoma].
AB  - Tumoral pulmonary embolism is among the causes of acute dyspnea in patients with
      neoplasia. This phenomenon, different to thrombotic embolism, occurs frequently
      in patients with lung, gastrointestinal, liver, breast and uterus neoplasia. It
      is usually asymptomatic and usually constitutes an autopsy finding in these
      patients. More rarely it manifests as a cor pulmonale which evolves subacutely.
      Exceptionally large tumoral emboli spread from a primary tumoral mass, and
      obstruct main pulmonary arterial vessels, causing a clinical picture
      indistinguishable from massive pulmonary thromboembolism. We present case of
      massive tumoral pulmonary embolism by an hepatocarcinoma. In spite of an early
      thrombolytic treatment the patient died from acute pulmonary hypertension.

PMID- 9518034
TI  - [Superior vena cava syndrome as initial manifestation of acute aortic dissection:
      a case report and review of the literature].
AB  - Aortic dissection usually presents with chest pain, abnormal pulses and a widened
      mediastinum on chest radiograph. It is rarely associated with the superior vena
      cava syndrome as the first manifestation. This paper presents a patient who had a
      superior vena cava syndrome as a result of a painless aortic dissection and
      compared with other previously reported cases.

PMID- 9518035
TI  - [Venous occlusion after catheterization of both subclavian veins for
      hemodialysis].

PMID- 9518036
TI  - [Pulmonary infiltrates and fever after intravesical instillation of BCG].

PMID- 9518037
TI  - [Multicentric plasma cell angiofollicular hyperplasia in a HIV-positive patient].

PMID- 9518038
TI  - [Toxic epidermal necrolysis and corticosteroid therapy].

PMID- 9518039
TI  - [Bilateral livedo reticularis and hemoptysis as a form of presentation of a case
      of disease caused by multiple cholesterol embolisms].

PMID- 9518040
TI  - [Fournier's gangrene. A case report].

PMID- 9518041
TI  - The importance of antibody specificity in measuring cross-linked fibrin
      degradation products by ELISA.
AB  - We and others have previously shown that plasma concentrations of XL-FDPs are
      accurately characterized with an enzyme-linked immunosorbent assay (ELISA) based
      on the monoclonal antibody DD-3B6/22, which is specific for D-dimer, and a pan
      specific tag antibody (DD-4D2/182) in patients with thrombotic disorders.
      However, in patients treated with fibrinolytic agents, increases in non-cross
      linked fibrin(ogen) degradation products are detected by the pan-specific tag
      antibody due to formation of complexes between non-cross-linked derivatives and
      XL-FDPs. Assays based on the use of fibrin degradation product-specific tag
      antibodies appear to be more specific, but whether they would be clinically more
      informative is unclear. Accordingly, in the current study we measured
      concentrations of XL-FDPs with two ELISAs; one based on the pan-specific tag
      antibody (DD-4D2/182) and another based on a fibrin degradation product-specific
      tag antibody (DD-1D2/48) in patients treated with three well-characterized
      thrombolytic regimens: one associated with minimal fibrinogenolysis (100 mg
      tissue-type plasminogen activator [t-PA]) over 3 h), moderate fibrinogenolysis
      (100 mg t-PA over 90 min), and one with marked fibrinogenolysis (1.5 MU
      streptokinase [SK]). In patients treated with t-PA, increases in XL-FDPs were
      closely correlated with fibrinogenolysis, as characterized by increases in the
      concentration of the Bbeta1-42 peptide, when measured with the pan-specific tag
      ELISA (r = 0.7), but not when measured with the fibrin degradation product
      specific tag assay (r = 0.2). In patients treated with SK, concentrations of XL
      FDPs were significantly higher (> 2000 ng/ml) with the pan-specific tag ELISA
      compared with the fibrin degradation product-specific tag ELISA (< 1000 ng/ml) 1,
      2 and 8 h after start of the infusion (P < 0.01). Concentrations of XL-FDPs were
      also higher in patients treated with SK compared with t-PA when measured with the
      pan-specific tag ELISA, but lower with SK with the fibrin-specific ELISA (P <
      0.01). The value of measurement of XL-FDPs in patients treated with fibrinolytic
      agents will need to be reappraised with the use of fibrin degradation product
      specific assays, which appear to provide more accurate information on the
      kinetics of cross-linked fibrin lysis in patients treated with t-PA or SK.

PMID- 9518042
TI  - Absence of cross-reactivity of SR90107A/ORG31540 pentasaccharide with antibodies
      to heparin-PF4 complexes developed in heparin-induced thrombocytopenia.
AB  - New carbohydrate-based anticoagulants devoid of the side effects of
      unfractionated heparin are currently under development and show a major potential
      for patients with heparin-induced thrombocytopenia (HIT) who still require
      efficient antithrombotic therapy. As HIT is usually associated with antibodies to
      heparin-platelet factor 4 (H-PF4) complexes, cross-reactivity of the heparin
      pentasaccharide SR90107A/ORG31540 was tested in the presence of PF4 with the
      plasma from 49 patients with HIT. No cross-reactivity was observed whatever the
      pentasaccharide concentrations. Although more extensive studies are required for
      excluding its total absence of immunogenicity and pathogenicity, this
      pentasaccharide is a candidate for use in emergency situations in patients with
      HIT.

PMID- 9518043
TI  - Resistance to activated protein C and low levels of protein S activity in nine
      thrombophilic families: a correct diagnosis.
AB  - In order to define the thrombophilic conditions related to activated protein C
      resistance (APC-R) and protein S (PS) deficiency and to detect the possible
      combination of these defects, we studied nine unrelated patients selected because
      of low anticoagulant response to APC and reduced PS activity with at least one
      first degree relative having the same coagulation feature. The mean APC ratio was
      0.64 (normal values > 0.80) and range 0.35-0.80. Three of the patients were
      heterozygous and two were homozygous for the Leiden mutation (FVR506Q); in the
      remaining four there was no mutation. The mean PS activity was 41.6% and range 32
      54 (normal 65-150%). Five of the patients had low PS activity despite normal
      total and free antigenic levels, and normal activity when measured at higher
      plasma dilution; these were carrying at least one gene for the Leiden mutation.
      In the remaining four patients the crossed-immunoelectrophoresis and the Western
      blotting analysis showed a type I PS deficiency confirmed by the familial
      restriction fragment length polymorphism analysis. Thus, four families were
      diagnosed with the type I PS defect and five with congenital APC-R. No combined
      PS/FV Leiden or type II PS defect was found. The only defect found was in the
      anticoagulant PC pathway. We therefore designed a procedure to diagnose
      thrombophilic conditions related to this pathway. This study indicates that a
      specific methodological approach must be used to accurately characterize APC-R
      and PS deficiency and that care is necessary to avoid the possibility of
      misdiagnosis.

PMID- 9518044
TI  - The interaction of recombinant tissue type plasminogen activator and recombinant
      plasminogen activator (r-PA/BM 06.022) with human endothelial cells.
AB  - The Escherichia coli-expressed recombinant plasminogen activator (r-PA)
      comprising the kringle 2 and protease domains of human tissue-type plasminogen
      activator (t-PA) has a four-fold longer half-life time in the circulation than t
      PA, possibly resulting in an increased opportunity for r-PA to interact with the
      endothelial lining. In the present study we investigated the interaction of r-PA
      and t-PA with human umbilical vein endothelial cells (HUVEC). Specific binding of
      125I-t-PA and 125I-r-PA were similar at 4 degrees C (Kd 6 nmol/l; Bmax about 120
      fmol/mg cell protein). About half of the specific binding sites were shared by t
      PA and r-PA, because unlabeled t-PA and r-PA competed equally with 125I-labeled t
      PA and r-PA for binding to HUVEC. The low affinity interaction of 125I-t-PA was
      several-fold higher than that of 125I-r-PA. When PA binding was studied at 37
      degrees C, HUVEC bound more t-PA than r-PA to both specific and non-specific
      binding sites. Both t-PA and r-PA were internalized and degraded, but t-PA
      internalization proceeded more efficiently than that of r-PA. In the presence of
      100 microM chloroquine, the degradation of t-PA and r-PA was inhibited by 75% and
      40%, respectively, indicating lysosomal degradation. When the active sites of t
      PA and r-PA were blocked by PPACK, part of the cell association and most of the
      degradation of both t-PA and r-PA were inhibited. This points to plasminogen
      activator inhibitor-1 (PAI-1) as one of the specific binding sites. A possible
      role of LDL-receptor related protein (LRP) or related members of this receptor
      family was investigated by using the 39 kD receptor associated protein (RAP)
      which prevents interaction of ligands with these receptors. RAP reduced the
      association of 125I-t-PA by 25% and the degradation of 125I-t-PA and 125I-r-PA by
      65% and 50%, respectively. Our data show that both t-PA and r-PA bind to HUVEC
      and can subsequently be internalized and degraded. However, r-PA interacts less
      effectively with HUVEC than t-PA. This indicates that binding to the endothelium
      does not prevent the clearance of r-PA and is not the cause of its long half
      life.

PMID- 9518045
TI  - A murine model of factor XI deficiency.
AB  - To facilitate investigations into the physiologic and pathologic roles of factor
      XI, we have developed a murine model of severe factor XI deficiency using the
      technique of homologous recombination in embryonic stem cells. The factor XI gene
      was disrupted by introducing a neomycin phosphotransferase gene into the fifth
      exon. The activated partial thromboplastin times of homozygous null mice were
      prolonged (158- > 200 s) compared with wild type (25-34 s) and heterozygous null
      (40-61 s) litter mates. Factor XI activity was absent from the plasma of mice
      homozygous for the null mutation and factor XI mRNA was undetectable by Northern
      blot and reverse transcription/PCR in the livers of homozygous null animals. The
      genotypes of progeny from matings of mice heterozygous for the factor XI null
      allele followed the expected Mendelian ratio (1:2:1, wild type 26%, heterozygote
      null 54%, homozygous null 20%), indicating that severe factor XI deficiency did
      not result in increased intrauterine death. Results of a tail transection
      bleeding time assay were similar for wild type and homozygous null animals with,
      at most, a tendency for slightly prolonged bleeding in the homozygous null
      animals. The factor XI deficient mice are a unique tool for evaluating the role
      of factor XI in normal hemostasis and pathologic coagulation.

PMID- 9518046
TI  - Five antithrombin variants, four associated with thrombosis.
AB  - We have identified five mutations in antithrombin by direct sequencing of exons
      amplified using polymerase chain reaction. Four of these mutations are associated
      with thrombosis, three cause type I antithrombin deficiency and one has features
      of a type II deficiency. The fifth variant appears to have no functional
      consequences. The type I mutations are in exon 2, exon 3b and exon 4. The first
      of these is a nonsense mutation causing substitution of a Tyr-->stop at position 
      16 within the secretion signal sequence. The second is a missense mutation
      resulting in the substitution Cys-->Ser at position 247. This disrupts the
      disulphide bond with Cys 430 leaving a free cysteine residue and the C-terminus
      unconstrained. The third type I mutation is an in-frame deletion resulting in the
      loss of Ile 186. This is a highly conserved residue in the serpin superfamily and
      will predictably result in the disruption of the F-helix. The fourth mutation, in
      exon 3a, results in the substitution of Ser 162 by Asn. This residue is sited in
      the E-helix and the replacement of the buried side chain of serine by the larger
      asparagine side chain will predictably cause structural perturbation. The last
      example, Val 415-->Asp, was an incidental finding as a follow up investigation of
      a nephrotic patient. Although one other member of the family also had the
      mutation there was no linked history of thrombotic disease.

PMID- 9518047
TI  - Acute stroke in a young female with anti-human beta2-glycoprotein I antibodies.
AB  - We report the case of a woman who, at the age of 27, developed a cerebral
      arterial occlusion. The laboratory investigations showed an anti-human beta2
      glycoprotein I antibody, but no other biological sign of antiphospholipid
      antibody syndrome or autoimmune disorders. The patient otherwise presented with
      diabetes and moderate obesity. The species specificity of anti-beta2-glycoprotein
      I antibodies probably explains the discrepancy between false negative results for
      antiphospholipid antibodies assayed by clotting and ELISA studies and positivity
      for anti-human beta2-glycoprotein I. Further studies will be important to
      evaluate the frequency of such antibodies, as well as their value as a risk
      factor for venous and arterial thrombosis, and their signification within the
      antiphospholipid antibody syndrome.

PMID- 9518048
TI  - Acquired APC resistance related to oral contraceptives and pregnancy and its
      possible implications for clinical practice.

PMID- 9518049
TI  - Cancer procoagulant: a factor X activator, tumor marker and growth factor from
      malignant tissue.
AB  - Hemostatic abnormalities associated with malignant disease led to the search for
      and discovery of a proteolytic enzyme that activated factor X in the blood
      coagulation cascade. It was named cancer procoagulant (CP). CP is a cysteine
      proteinase that is found in malignant and fetal (human amnion-chorion) tissue; it
      has not been found in normally differentiated tissue. It is a calcium-dependent,
      Mn2+ stimulated enzyme that has enhanced activity and inhibition in a reduced
      environment. This review presents a complete compilation and discussion of the
      known chemical and enzymatic characteristics of CP as well as many purification
      and assay procedures. Several unique properties of these procedures are
      described. Some problems and controversies are highlighted in each of the
      sections. An immunoassay for CP as a tumor marker and some of its potential
      applications in the diagnosis and monitoring of cancer are reviewed. Some
      therapeutic implications of CP are noted in light of the observation that
      antibodies to CP block the metastatic seeding of lung colonies in vivo and
      diminish the viability of tumor cells in vitro. Finally, comments about the
      relationship between tissue factor and CP in the malignant cells are provided.

PMID- 9518050
TI  - Partial identification of the epitope on D-dimer for monoclonal antibody, DD
      3B6/22.
AB  - This study provides new information about the recognition site on fibrin for DD
      3B6/22, a monoclonal antibody used in the diagnosis of thrombotic disease and
      proposed as a delivery agent for radioisotopes to visualize thrombi in situ.
      Preliminary chemical modification and proteolytic digestion of D-dimer revealed
      key residues in the interaction of D-dimer with its diagnostic antibody DD
      3B6/22. Following the initial survey, thermolysin was used to produce digestion
      fragments for more specific sequence analysis. The gamma-polypeptide chain of D
      dimer was confirmed as a recognition site for the antibody, with the residues
      S86RK88 being implicated in binding, and a second, novel site of antibody
      interaction was identified on the alpha-polypeptide as D105NTYNR110. Based on
      evidence from this study and from a previous investigation of the DD-3B6/22
      binding site on D-dimer (Devine and Greenberg), a model for the DD-3B6/22 binding
      site is proposed to comprise regions from parts, at or near the N-terminus, of at
      least two different subunits: one region on the alpha-polypeptide chain of one D
      monomer and another region on the gamma-polypeptide chain of an adjacent D
      monomer. The model is discussed in the context of the predicted secondary and
      tertiary structure of D-dimer.

PMID- 9518051
TI  - Factor XIIa activation of plasminogen is enhanced by contact activating surfaces
      and Zn2+.
AB  - The native form of plasminogen is Glu-plasminogen, which by plasmin cleavage
      gives Lys-plasminogen. Lys-plasminogen is a considerably better substrate
      compared with Glu-plasminogen for plasminogenolytic enzymes. The contact
      activation of the intrinsic pathway of coagulation consisting of factor XII,
      prekallikrein and high Mr kininogen has been implicated to play a role in the
      intrinsic fibrinolysis. Here activation of Glu- and Lys-plasminogen by factor
      XIIa in the absence of prekallikrein/kallikrein and high Mr kininogen was studied
      in a purified system by the generation of amidolytic activity towards pyroGlu-Phe
      Lys-pNA (S-2403), a chromogenic substrate of plasmin. A slow activation rate of
      both Glu- and Lys-plasminogen by factor XIIa was enhanced approximately 60-fold
      in the presence of Zn2+ and a negatively charged surface. 6-Aminohexanoic acid
      further enhanced the activation of Glu-plasminogen but inhibited the activation
      of Lys-plasminogen. The presence of a specific factor XIIa inhibitor completely
      prevented the generation of plasmin amidolytic activity indicating that
      activation was mediated by proteolytical cleavage, although this could not be
      proven by Western-blotting. Physiological concentration of factor XIIa was as
      more efficient than soluble u-PA to lyse fibrin as a result of activation of Glu
      plasminogen. This did not require the presence of Zn2+ or sulfatide.

PMID- 9518052
TI  - High resolution transmission electron microscopic study of some low-dimensional
      nanostructures.
AB  - High-resolution transmission electron microscopy (HRTEM) study of some low
      dimensional nanostructures, such as carbon nanotubules and silicon-based blue
      light emitting beta-SiC nanoparticles will be reported. We have shown that nested
      hollow tubules formed by successive cylindrical graphite sheets are found,
      frequently, to be polyhedral or elliptical in cross-section, which are
      perpendicular to the tube-axis. Varied spacing between adjacent tube sheets is
      observed and edge-type dislocations can be distinguished in some tubules. These
      abnormal structural features are related to accommodations of various strains
      taking place simultaneously in tube sheets. Blue-light emitting porous beta-SiC
      formed by C+ implantation of a single crystal silicon wafer have also been
      investigated. Buried layer structures with different beta-SiC concentration were
      formed in the implanted silicon substrate. These beta-SiC nano-particles are 2-8
      nm in size and formed epitaxially from the upper and lower damaged layers,
      respectively, but randomly in the middle layer. The structural characteristics of
      the layered structure may be responsible for the blue-light emitting effect of
      the porous beta-SiC material.

PMID- 9518053
TI  - High resolution electron microscopy investigations of interface and other
      structure defects in some ceramics.
AB  - Interface, grain boundary, and other structure defects are the most important
      structural factors to affect the properties of ceramics materials. The present
      paper shows the relationship between the properties and those structure features
      such as grain boundaries, phase boundaries, interfaces, twins, intergrowths,
      dislocations, point defect aggregates, order-disorder, and other structure
      defects in different kinds of ceramics materials. At present this research
      covers: C60, sialon-based ceramics (alpha-sialon/SiC(w) composite, Y-alpha
      sialon/beta-sialon composite), high Tc superconductors (YBa2Cu3O7, YBa2Cu4O8,
      Bi2Sr2CaCu2O8, Bi2Sr2Ca2Cu3O10), and bioceramics (hydroxyapatite, chlorapatite)
      and so on. The structure features mentioned above were characterized by high
      resolution electron microscopy; so the structure details are at an atomic level
      and the related physical, chemical, engineering, even biological phenomena can be
      understood at an atomic and molecular level.

PMID- 9518054
TI  - (110) HREM of interfacial structures in semiconductor hetero-structures.
AB  - We have established a (110) cross-sectional high-resolution transmission electron
      microscopy (HREM) method to observe atomic structures of semiconductor hetero
      interfaces. We show theoretically that the semiconductors in a hetero-structure
      exhibit strong contrast for an EM specimen thickness near their extinction
      distances, allowing atomic-scale observations of the interfacial structures
      between them. Furthermore, to obtain a clear HREM image, an EM specimen
      preparation technique is developed in which chemical etching is used to remove
      ion milling artifacts. This HREM method allows edge-on imaging of interfaces
      formed along the (110) direction; observations of atomic steps at AlAs/GaAs
      interfaces and a chemically ordered structure at Si/Ge interfaces are
      demonstrated.

PMID- 9518056
TI  - [The differential gene expression of the Six family during limb regeneration and
      development in amphibians].
AB  - Differential expression of homeobox genes of the Six family, homologues of
      Drosophila gene sine oculis, was revealed during limb regeneration of ribbed newt
      Pleurodeles waltlii and common frog Rana temporaria. Expression of these genes
      correlated to regeneration capacity in the studied animals. The primary structure
      of the most conservative region in the identified genes has been determined. We
      assessed the differences in the primary structure of Six family genes obtained
      from regenerating limbs of the newt and frog (86 and 94.9% similarity at the
      nucleotide and amino acid levels, respectively). Comparison of the obtained and
      published sequences of Six family genes has demonstrated that they are most
      similar to mouse gene Six1 (84.2 and 82.8% nucleotide sequence similarity in the
      frog and newt, respectively, and 99.2 and 94.1% amino acid sequence similarity in
      the frog and newt, respectively.

PMID- 9518057
TI  - [The taxonomy of the musk deer (Artiodactyla, Mammalia)].
AB  - The results of multiyear studies (1976-1996) of musk deer taxonomy and the
      published data were generalized. Two groups of subspecies were isolated on the
      basis of statistical analysis of 13 linear measurements and six indices in 388
      skulls from different parts of the range. Group "sibirica" includes four
      subspecies: Siberian Moschus moschiferus moschiferus F., Verkhoyansk M.
      moschiferus articticus F., Far-Eastern M. moschiferus turowi Zal., and Sakhalin
      M. moschiferus sachalinensis F. Group "himalaica" contains three subspecies:
      Korean M. moschiferus parvipes Hol., Chinese M. moschiferus chrysogaster H., and
      Himalayan Moschus moschiferus leucogaster H.

PMID- 9518055
TI  - High resolution transmission electron microscopy studies of metal/ceramics
      interfaces.
AB  - When single crystals of two different materials are in contact at a sharp
      interface, the orientation relationship between them is said to be epitaxial and
      the configuration of the atoms at the two sides of the interface is such that the
      lattice mismatch between them is accommodated in the least energetic way. Among
      other factors, this depends on the bonding between the atoms on the two sides of
      the interface. In this paper, the relaxation of strain in thin films grown
      epitaxially on dissimilar substrates is first discussed theoretically for cases
      of small and large lattice mismatch. In a following section, two metal-ceramics
      heteroepitaxial systems are investigated in detail by various techniques of
      transmission electron microscopy. One case, vanadium on MgO, corresponds to a
      small-mismatched system and the interface changes from coherent to semicoherent
      above a critical thickness; this turns out to be much larger than the expected
      value. In the other case-vanadium on the basal and rhombohedral (R) planes of
      sapphire-the lattice mismatch is large and misfit dislocations exist from the
      very initial stages of deposition. It is argued that although misfit dislocations
      in small and large lattice-mismatched systems are geometrically similar, their
      physical nature is different.

PMID- 9518058
TI  - [History of the study of and the current data on the geographic range of the
      greater gerbil (Rhombomys opimus Licht., 1823) in Mongolia].
AB  - The history of studies of the great gerbil range was analyzed and position of the
      range boundaries was made more precise on the basis of the published data, museum
      collections, various natural maps, and authors' field observations. A scheme of
      the range regionalization is presented, in which three regional complexes of
      autonomous population groups are distinguished: Djungarian, Central Gobi, and
      East Gobi-Alashan'. Five autonomous population groups have also been isolated,
      which are located to the north of the main range: Shargin Gobi (?), Beger-nur,
      Orok-nur, Bulgan, and Bayan-dov. Regions with most favorable conditions for the
      great gerbil colonies were also shown.

PMID- 9518059
TI  - [The action of epidermal growth factor on the migration of A-431 cells].
AB  - It has been demonstrated that the epidermal growth factor (EGF) stimulates
      migration of A-431 cells into the wound created in a monolayer in the absence of
      any significant effect on the incorporation of labeled thymidine into cells. The
      effect of EGF on migration is stimulated by the simultaneous addition of insulin.
      Cell treatment with mitomycin C completely eliminates the stimulating effect of
      EGF, without, however, affecting baseline level of cell migration, which is
      independent on growth stimulants. These results lead to the conclusion that the
      effect of EGF on cell migration and cell proliferation in A-431 culture can be
      partially separated.

PMID- 9518060
TI  - [The destruction of microscopic organisms by their irradiation with a special
      form of UHF electromagnetic signals].
AB  - Electromagnetic signals of special form produced by an ultra-high frequency
      generator were used to destroy various microorganisms: baker's yeast; blue-green
      alga Nostoc muscorum; mold fungus; and two flagellates, plant flagellate Euglena
      gracilis and an animal flagellate parasitizing on humans. The control samples
      before irradiation and experimental samples damaged and destroyed by irradiation
      were examined on a microscope with a computer system of image analysis. The
      results are presented as computer graph images.

PMID- 9518061
TI  - [The formation of the human epiphysis and its dynamic development at the stage of
      early embryonic differentiation].
AB  - We studied the epiphysis of human embryos at stages from 18 to 63 mm of occipital
      sacral length (OSL). We found that the epiphysis is formed by migration of cells
      from the roof of the diencephalon in the dorso-caudal direction. At this time,
      the epiphysis undergoes active vascularization, initially through pinealocytes
      filling the space between capillaries, and then by the ingrowth of the bundle of
      nerves and vessels into the epiphysis. The nerve entering the epiphysis, together
      with vessels, subsequently becomes a source of innervation for the epiphysis of
      the adult human. Analysis of qualitative correlations between epiphysis
      development and linear growth of the embryo has demonstrated that the rate of the
      increase of epiphyseal volume is significantly higher than the rate of the
      increase of the embryo's occipital-sacral length. Asynchrony in the rate of
      growth of epiphysis and embryo is highly individual, since increase in volume per
      1 mm of length may differ at different stages by a factor of two or even more.

PMID- 9518062
TI  - A kinetic and ESR investigation of iron(II) oxalate oxidation by hydrogen
      peroxide and dioxygen as a source of hydroxyl radicals.
AB  - The reaction of Fe(II) oxalate with hydrogen peroxide and dioxygen was studied
      for oxalate concentrations up to 20 mM and pH 2-5, under which conditions mono-
      and bis-oxalate complexes (Fe[II](ox) and Fe[II](ox)2[2-]) and uncomplexed Fe2+
      must be considered. The reaction of Fe(II) oxalate with hydrogen peroxide (Fe2+ +
      H2O2 --> Fe3+ + .OH + OH-) was monitored in continuous flow by ESR with t-butanol
      as a radical trap. The reaction is much faster than for uncomplexed Fe2+ and a
      rate constant, k = 1 x 10(4) M(-1) s(-1) is deduced for Fe(II)(ox). The reaction
      of Fe(II) oxalate with dioxygen is strongly pH dependent in a manner which
      indicates that the reactive species is Fe(II)(ox)2(2-), for which an apparent
      second order rate constant, k = 3.6 M(-1) s(-1), is deduced. Taken together,
      these results provide a mechanism for hydroxyl radical production in aqueous
      systems containing Fe(II) complexed by oxalate. Further ESR studies with DMPO as
      spin trap reveal that reaction of Fe(II) oxalate with hydrogen peroxide can also
      lead to formation of the carboxylate radical anion (CO2-), an assignment
      confirmed by photolysis of Fe(II) oxalate in the presence of DMPO.

PMID- 9518063
TI  - Factors affecting events during oxidation of low density lipoprotein: correlation
      of multiple parameters of oxidation.
AB  - The present study shows that copper oxidation of LDL is a tightly-ordered process
      which can be finely controlled by appropriate selection of duration of oxidation
      and of concentrations of LDL and copper. Oxidation of LDL (0.1-2.0 mg LDL
      protein/ml) was carried out by copper catalysis (in the ratio of 2.5 microM Cu2+
      to 0.1 mg LDL protein/ml) in phosphate-buffered saline, and was monitored by
      agarose gel electro-phoresis, gas chromatography (GC), anion exchange fast
      protein liquid chromatography (FPLC), fluorescence spectroscopy and dynamic light
      scattering. Analysis of the data showed strong cross correlations between many of
      the parameters of oxidation. Oxidation was more rapid for lower concentrations
      than for higher concentrations of LDL, despite the same ratio of copper to LDL
      being employed. Chemical kinetics analysis of the GC data suggested that 7beta
      hydroxycholesterol formation occurred as a first order (or pseudo first order)
      consecutive reaction to the oxidation of linoleate. The first order rate
      constants for decomposition of linoleate and production of 7beta
      hydroxycholesterol correlated closely with the theoretically-calculated times
      between collision of LDL particles. LDL particle diameter, measured by dynamic
      light scattering, increased by ca. 50% over 24 h oxidation, suggesting unfolding
      of apo B-100. Prolonged oxidation of LDL at low concentration suggested that the
      radical chain reaction was able to propagate, albeit slowly, on cholesterol after
      all the polyunsaturated fatty acid was consumed. For higher concentrations of
      LDL, prolonged oxidation resulted in partial aggregation. These findings are
      applicable to preparing oxidised LDL with different degrees of oxidation, under
      controlled conditions, for studying its biological properties.

PMID- 9518064
TI  - Erucic acid and erucic acid anilide-induced oxidative burst in human
      polymorphonuclear leukocytes.
AB  - Human polymorphonuclear leukocytes (PMNL) were exposed to erucic acid or erucic
      acid anilide to explore their effects on the production of reactive oxygen
      species (ROS) and the levels of free intracellular calcium. The compounds did not
      change the levels of intracellular calcium, but both dose-dependently induced
      respiratory burst in PMNL. Maximal production of ROS by erucic acid exceeded that
      induced by its anilide 13-fold. A protein kinase C inhibitor, Ro 31-8220,
      completely inhibited erucic acid and erucic acid anilide-induced production of
      ROS. Neither erucic acid nor erucic acid anilide modified FMLP-induced production
      of ROS. However, erucic acid (500 microM) amplified 5 nM PMA-induced ROS
      production 1.8-fold, but did not have this effect at a lower PMA concentration.
      On the contrary, erucic acid anilide inhibited PMA-induced oxidative burst, and
      shifted the peak ROS production induced by PMA to a later time-point. The present
      results show that aniline moiety modifies the effects of erucic acid on the
      activation of PMNL, and suggest that both erucic acid and erucic acid anilide may
      activate PMNL through a protein kinase C-dependent mechanism.

PMID- 9518065
TI  - On the cytoprotective role of ferritin in macrophages and its ability to enhance
      lysosomal stability.
AB  - Macrophages have a great capacity to take up (e.g. by endocytosis and
      phagocytosis) exogenous sources of iron which could potentially become cytotoxic,
      particularly following the intralysosomal formation of low-molecular weight,
      redox active iron, and under conditions of oxidative stress. Following
      autophagocytosis of endogenous ferritin/apoferritin, these compounds may serve as
      chelators of such lysosomal iron and counteract the occurrence of iron-mediated
      intralysosomal oxidative reactions. Such redox-reactions have been shown to lead
      to destabilisation of lysosomal membranes and result in leakage of damaging
      lysosomal contents to the cytosol. In this study we have shown: (i) human
      monocyte-derived macrophages to accumulate ferritin in response to iron exposure;
      (ii) iron to destabilise macrophage secondary lysosomes when the cells are
      exposed to H2O2; and (iii) endocytosed apoferritin to act as a stabiliser of the
      acidic vacuolar compartment of iron-loaded macrophages. While the endogenous
      ferritin accumulation which was induced by iron exposure was not sufficient to
      protect cells from the damaging effects of H2O2, exogenously added apoferritin,
      as well as the potent iron chelator desferrioxamine, afforded significant
      protection. It is suggested that intralysosomal formation of haemosiderin, from
      partially degraded ferritin, is a protective strategy to suppress intralysosomal
      iron-catalysed redox reactions. However, under conditions of severe macrophage
      lysosomal iron-overload, induction of ferritin synthesis is not enough to
      completely prevent the enhanced cytotoxic effects of H2O2.

PMID- 9518066
TI  - A peroxidase-catalyzed sulfoxidation of promethazine.
AB  - Lactoperoxidase, when incubated with increasing amounts of promethazine (P) and
      promethazine sulfoxide (PO) catalyzes the formation of promethazine sulfoxide
      accompanied by oxygen consumption. An intermediate radical of PO can be detected
      by electron spin resonance (ESR). Catalase or superoxide dismutase do not inhibit
      the reaction while dopamine does. The lactoperoxidase-catalyzed formation of
      dopaminochrome in the presence of hydrogen peroxide is inhibited by P. Both P and
      PO inhibit acetyl- and butyrylcholinesterase. Purified enzymes were used
      throughout the study and horseradish peroxidase but not myeloperoxidase had an
      activity similar to that of lactoperoxidase.

PMID- 9518067
TI  - Appearance of electron spin resonance signals in the interaction of
      dithiocarbamate-Fe(II) with nitrogen dioxide and nitrite.
AB  - Whether dithiocarbamate-Fe(II) complexes used in the electron spin resonance
      (ESR) studies are specific for the detection of NO was investigated. It was found
      that the typical ESR signals of dithiocarbamate-Fe(II)-NO spin adducts appeared
      in the interaction of N-methyl-D-glucaminedithiocarbamate (MGD)-,
      bis(hydroxyethyl) dithiocarbamate (HED)- and diethyldithiocarbamate (DED)-Fe(II)
      complexes with the NO-derived nitrogen oxides, nitrogen dioxide (NO2) and nitrite
      ion (NO2-) in a prolonged incubation. Under the conditions of prolonged
      incubation, appearance of the ESR signals of the dithiocarbamate-Fe(II)-NO spin
      adducts may indicate the presence of not only NO but NO2 and NO2-.

PMID- 9518068
TI  - Will the 'good fairies' please prove to us that vitamin E lessens human
      degenerative disease?
AB  - Recent research about the role of free radical derivatives of oxygen and nitrogen
      in biological systems has highlighted the possibility that antioxidants, such as
      vitamin E, that prevent these processes in vitro may be capable of carrying out a
      similar function in living organisms in vivo. There is increasing evidence that
      free radical reactions are involved in the early stages, or sometimes later on,
      in the development of human diseases, and it is therefore of particular interest
      to inquire whether vitamin E and other antioxidants, which are found in the human
      diets, may be capable of lowering the incidence of these diseases. Put simply,
      the proposition is that by improving human diets by increasing the quantity in
      them of antioxidants, it might be possible to reduce the incidence of a number of
      degenerative diseases. Of particular significance to these considerations is the
      likely role of the primary fat-soluble dietary antioxidant vitamin E in the
      prevention of degenerative diseases such as arteriosclerosis, which is frequently
      the cause of consequent heart attacks or stroke, and prevention of certain forms
      of cancer, as well as several other diseases. Substantial evidence for this
      proposition now exists, and this review is an attempt to give a brief account of
      the present position. Two kinds of evidence exist; on the one hand there is very
      substantial basic science evidence which indicates an involvement of free radical
      events, and a preventive role for vitamin E, in the development of human disease
      processes. On the other hand, there is also a large body of human epidemiological
      evidence which suggests that incidence of these diseases is lowered in
      populations having a high level of antioxidants, such as vitamin E, in their
      diet, or who have taken steps to enhance their level of intake of the vitamin by
      taking dietary supplements. There is also some evidence which suggests that
      intervention with dietary supplements of vitamin E can result in a lowered risk
      of disease, in particular of cardiovascular disease, which is a major killer
      disease among the developed nations of the world. The intense interest in this
      subject recently has as its objective the possibility that, by making some simple
      alterations to dietary lifestyle, or by enhancing the intake of vitamin E by
      fortification of foods, or by dietary supplements, it may be possible to reduce
      substantially the risk of a large amount of common, highly disabling human
      disease. By this simple means, therefore it may be possible to improve
      substantially the quality of human life, in particular for people of advancing
      years.

PMID- 9518069
TI  - Ex vivo assessment of lymphocyte antioxidant status using the comet assay.
AB  - Lymphocytes were isolated from volunteers before and after receiving a single
      supplement of vitamin C, vitamin E or beta-carotene. The lymphocytes were treated
      with H2O2, and DNA strand breaks were measured by single cell gel electrophoresis
      (the comet assay). Significant protection against oxidative DNA damage was
      evident 2-4 h after vitamin C intake, and 18-24 h after consumption of the other
      antioxidants. Lymphocytes from smokers were more sensitive to DNA damage than
      those from non-smokers, and they showed at least as great a protective effect
      with antioxidants.

PMID- 9518071
TI  - Proceedings of the 2nd International Symposium on the Etiology and Pathobiology
      of Transplant Vascular Sclerosis. Bermuda, March 1997.

PMID- 9518070
TI  - Auditing audit: the cost of the emperor's new clothes.

PMID- 9518072
TI  - Gene therapy and arthritis.

PMID- 9518073
TI  - Murmurs from the heart (or why the stethoscope is not an economic tool)

PMID- 9518074
TI  - [Microsurgical methods of restoration of finger flexor tendon functions with the
      cicatricial transformation of surrounding tissues using complex flaps].
AB  - Experience of treatment of 115 patients with late consequences of the fingers
      flexors tendons traumatic damage, complicated by cicatricial transformation of
      soft tissues was reflected. Results of application of methods using microsurgical
      autotransplantation of complex flaps to replace the cicatricial and necrotic
      purulent defects of soft tissues with subsequent autotendoplasty were analyzed.
      Method of treatment providing the tendons isolation from the cicatricial tissues
      for the functional results improvement, elaborated in the department of
      microsurgery and plastic surgery, is presented.

PMID- 9518075
TI  - [A case of pancreatic teratoma].

PMID- 9518076
TI  - [Oberling's retroperitoneal xanthogranuloma].

PMID- 9518077
TI  - [A case of umbilical endometriosis].

PMID- 9518078
TI  - [Difficulties in diagnosis of phagodenic hard canker].

PMID- 9518079
TI  - [A case of duodenal ileus, caused by pseudotumor].

PMID- 9518080
TI  - [A rare complication of umbilical cord hernia].

PMID- 9518081
TI  - [The use of laser correlational spectroscopy in differential diagnosis of acute
      cholecystitis and viral hepatitis].

PMID- 9518082
TI  - [Minimal access cholecystectomy].

PMID- 9518083
TI  - [Co-occurrence of double aortic arch with mucopolysaccharidosis in an infant].

PMID- 9518084
TI  - [Acute retrocecal appendicitis after nephrectomy].

PMID- 9518085
TI  - [Leukocyte chemoluminescence of the whole blood in patients with open angle
      glaucoma].

PMID- 9518086
TI  - [In memory of Professor Boris Efimovich Frankenberg (100th anniversary of his
      birthday)].

PMID- 9518087
TI  - [The administration of peflocine (pefloxacin) in the treatment and prevention of
      surgical infections].
AB  - The results of treatment of 23 patients with pefloxacin, administered because of
      the infectional complications in surgery development (1 group), and of 11
      patients --for the infection development prophylaxis (2 group) were discussed. In
      the first group the recovery was noted in 83.3%, and significant improvement of
      condition--in 16.7% of patients. In the second group the infectional
      complications in postoperative period were absent.

PMID- 9518088
TI  - [Effect of ultrasonic treatment on the purulent inflammatory process].

PMID- 9518089
TI  - [Peritoneostomy treatment of postop suppurative wounds in patients with
      peritonitis].
AB  - In 60 patients with severe form of peritonitis, treated with peritoneostomy
      application, were studied up the peculiarities of the abdominal wall
      postoperative wounds suppuration concerning its clinical course and treatment.
      For the local treatment of purulent wounds the electrochemically activated
      potassium chloride solution anolyte fraction (EHAR-anolyte) was applied.

PMID- 9518090
TI  - [Relaparotomy in the surgical treatment of early acute postoperative ileus].
AB  - The experience of 71,588 patients surgical treatment was summarized, of whon in
      1049 (1.47%) the relaparotomy conduction necessity have occurred, and in 411
      (0.57%)--in connection with acute early postoperative ileus (AEPOI) development.
      The timely diagnosis of developing AEPOI, adequate conduction of reoperation,
      expedient conduction of intensive therapy permitted to reduce the post-operative
      mortality for last 5 years from 29.4 to 14.3%.

PMID- 9518091
TI  - [Experience with muff-life esophagojejunal anastomosis].
AB  - The experience of 25-year period of gastrectomy conduction making a sleeve-like
      oesophago-jejunoanastomosis in 1778 patients was summarized. The anastomosis
      incompetence occurred in 16 (0.9%) patients. Refluxoesophagitis was revealed in
      6.3% of patients. High efficacy of the anastomosis was noted, providing
      antireflux defence and the portional chyme entering into jejunum.

PMID- 9518092
TI  - [Administration of sorbent blood in patients with acute gastrointestinal
      hemorrhage].
AB  - The treatment efficacy of sorbentic blood (SB) for the blood loss compensation in
      patients with an acute gastrointestinal hemorrhage (AGIH) was studied up. High
      efficacy of the SB transfusion in restoration of hematological and volumetric
      indexes and the acid-base state, providing clinical effect and lowering of the
      postoperative complications occurrence, was determined.

PMID- 9518093
TI  - [The prevention of postoperative adhesive pleuritis in patients with lung cancer
      as one of the approaches in clinical rehabilitation].
AB  - The method of postoperative pleural adhesions prophylaxis, using
      polymethylsiloxane-400 (PMS-400), was proposed and introduced in clinical
      practice. The method was applied in 42 patients with pulmonary cancer after
      explorative thoracotomies conduction and in 75 patients after radical operations.
      Complete effect (absent pleural adhesions) was achieved in 23% of patients,
      partial--in 48%. Reduce of protein losses with the exudate, more rapid
      restoration of the external respiration function and ability to work of radically
      operated patients was promoted by PMS-400 application.

PMID- 9518094
TI  - [Remote dynamic radiation thermography in the diagnosis of acute inflammatory
      diseases of the pancreatico-hepato-biliary tract].
AB  - The method of the remote radiation dynamic thermometry was elaborated usid
      information--diagnostic complex "Thermodyn". Among the examined patients there
      were 55 with cholecystitis, 20--with pancreatitis, 15--with
      cholecystopancreatitis, 65--healthy people. In chronic calculous cholecystitis in
      the remission stage the thermal stream density deviation from the mean for the
      abdominal cavity constituted 2.3%, in an acute stage--5.8%, in an acute
      cholecystitis--9.1%. In the patients with edematous form of acute pancreatitis
      the thermal stream density deviation in the pancreas projection was 10.2% of the
      median for the abdominal cavity, in pancreonecrosis--18.4%.
      Cholecystopancreatitis is characterized by the thermal stream density increase in
      epigastric region, both subcostal regions and in the pancreas projection.

PMID- 9518095
TI  - [The specifics of the diagnosis of hepatic trauma in a closed combined injury].
AB  - Examination was done to 196 injured persons with the closed abdominal trauma and
      hepatic injury. Reverse dependence between the trauma severity and frequency of
      abdominal symptoms exposure was established. Importance of rational use of
      instrumental diagnostical methods to reveal the hepatic injury timely was
      stressed.

PMID- 9518096
TI  - [Revascularization in the skin loss with skull fornix bone exposure].
AB  - Experience of 69 patients treatment, suffering the soft tissues death with
      uncovering or partial necrosis of the skull vault bones, occurring after burns
      and mechanical injuries was summarized. Multiple milling (4 patients) of the
      uncovered bones is dangerous, lacks efficacy, leads to osteomyelitis and the
      skull vault defects development. The skull bones revascularization with cutaneo
      subcutaneous, complex-composite flaps bringing nutrition from outside was
      proposed and accomplished. Revascularization methods are depicted, their results
      are presented in 65 patients. The revascularization conduction in term to 40 days
      after the injury occurrence permits to reduce the time of treatment, to avert the
      skull vault bones necroses, to gain good functional results.

PMID- 9518097
TI  - [Clinical-immunological research in chronic inflammatory diseases of the biliary
      tract].
AB  - Complex investigation of the immune state of 123 patients with chronic
      inflammatory diseases of biliary system (CDBS) was conducted. The reduce of T
      lymphocytes quantity and functional activity, their subpopulations, level of
      complement, the blood serum lysozyme, the increase of B-lymphocytes content,
      serumal IgG, IgM, circulating immune complexes (CIC), the antibodies titer to the
      gallbladder tissue, liver, pancreas, and level of the lymphocytes sensibilization
      to these antigens in the acute period of the disease. Presence of calculi in
      gallbladder, coexistence of cholecystitis with reactive hepatitis or pancreatitis
      caused more significant changes in immune system.

PMID- 9518098
TI  - [Ultrasonography for acute cholecystitis at a specialized surgical center].
AB  - Of 132 patients with the assumed acute cholecystitis diagnose 94 were operated
      on. Application of ultrasonic investigation and other noninvasive methods permits
      to determine for sure the acute cholecystitis diagnose, the form of gallbladder
      inflammation and stipulates the choice of treatment tactics and method of
      operation procedure.

PMID- 9518099
TI  - [Ways of improvement of surgical results for umbilical hernia in elderly and old
      patients].
AB  - The surgical treatment results of umbilical hernia in 116 patients aged from 60
      to 82 years was presented. Operation was done according to Mayo procedure while
      small hernia presented and middle size (22 patients) with the thinning zone width
      of aponeurosis up to 2 cm. The original hernioplasty procedure, with duplicature
      forming of the preliminary doubled aponeurosis edes in the hernia gates, was
      conducted in 48 patients with middle-size hernia and in 25 with large hernia
      while the thinning zone of aponeurosis constituted from 2 to 4 cm. While
      treatment of large and giant hernias with the aponeurosis thinned width over 4 cm
      was conducted the combined plasty usid autologous tissue (aponeurosis) and the
      implant (of polyurethane), placed into the duplicature of the hernial sac and
      fixated to aponeurosis from the abdominal cavity side. Hernia recidive was
      revealed in 2 (2.8%) of 72 patients followed up in term from 1 year to 5 years.
      The recurrence was not noted after the combined plasty conduction.

PMID- 9518100
TI  - [The basis of surgical treatment for extensive postoperative abdominal hernia].
AB  - The hernioplasty method was elaborated by the authors. The method stipulates the
      prosthesis of polyurethane placement in the duplicature from the hernial sac and
      parietal peritoneum and is sewn under the hernial defect edge, which are then
      sewn contactly. With the application of method elaborated 36 patients were
      operated on, suffering from large abdominal hernia. In 2 patients the
      lymphorhagia was observed in postoperative period during 9 days, in 1 the wound
      have suppurated and the prosthesis was removed. The late follow-up results were
      observed from 3 months till 3 years, the hernia recurrence was not revealed.

PMID- 9518101
TI  - [The choice of timing and methods in the surgical treatment of thoracic bone
      injuries in combined closed thoracic injuries during acute and early periods of
      traumatic disease].
AB  - Clinico-statistical analysis of the treatment results of 624 injured persons for
      the period from 1990 till 1995 year was conducted. In 509 (81.6%) of them the
      combined closed thoracic trauma was revealed, in 15 (18.4%)--the isolated closed
      affection of the skull, thorax, abdomen and extremities have occurred. The
      anatomic-functional model of the injury severity and prognosis outcome estimation
      was elaborated, an optimal timing and surgical treatment methods of the thoracic
      cage bones injury was substantiated, what have promoted to lower lethality from
      50%--in injured persons, operated on without taking into account the trauma
      severity and prognosis outcome, to 31.6%--in operated on in the postponed order.

PMID- 9518102
TI  - [The burn-resistant anti-autotoxic anti-immunocomplex serum].
AB  - On the ground of studying of autotoxin and the organism autointoxication in burn
      the antiburn antiautotoxic antiimmunocomplexes serum was elaborated. The serum
      application provides all of the experimental animals survival while the thermal
      burn, mortal for the control.

PMID- 9518103
TI  - [The role of antibacterial dissolving suture materials in the prevention of post
      resection syndromes].
AB  - Comparative clinical, endoscopic and bacteriological analysis of nonabsorbable
      and antibacterial absorbable suture materials application, which are used for
      gastroenteroanastomosis conduction after the stomach resection performance, was
      made. Application of antibacterial absorbable suture material is mandatory for
      postresection syndromes prophylaxis.

PMID- 9518104
TI  - [Current principles in the treatment of intestinal invagination in children].
AB  - Experience of treatment of 1345 children with invagination is summarized. On the
      ground of 271 patients examination data the reserves of the treatment improvement
      of this pathology were analyzed.

PMID- 9518105
TI  - [Surgical treatment of pulmonary hypoplasia in children].
AB  - The results of surgical treatment of 205 patients with pulmonary hypoplasia (PH)
      were analyzed. Indications for the intervention conduction were determined.
      Typical anatomic resection of the affected pulmonary zones was conducted in 143
      patients, combined resection--in 49, economical operation--in 13, bilateral
      pulmonary resection --in 3, reoperation--in 8.

PMID- 9518106
TI  - [Classification of burns based on depth of damage].
AB  - Now existing classifications of the burn wounds are studied up. An original
      variant of classification is proposed: I degree of the burn--epidermal; II degree
      -superficial dermal; III degree--deep dermal; IV degree--of deeply located soft
      tissues; V degree--of the bones and joints.

PMID- 9518107
TI  - [Clinical-morphological aspects of the adhesive disease progress in children].
AB  - The results of treatment of 60 children with complete adhesive ileus (CAI),
      occurring from 6 mo till 10 yrs after appendectomy conduction, were analyzed.
      Complex biochemical and immunological examination was conducted in 30 patients.
      There were 10 biopsies of parietal peritoneum examined. The obtained clinical,
      biochemical, immunological and morphological features may be applied for reliable
      prognostication of the CAI occurrence, complications course and outcome. Long
      observation and rehabilitational measures conduction is indicated in the patients
      with high risk of the peritoneal adhesive disease occurrence.

PMID- 9518108
TI  - [Functional diagnosis of chronic colostasis in children].
AB  - The functional methods of colon investigation in children are presented. Basing
      on the results of 313 patients examination the discernation of cologenic and
      terminal chronic colostases was proposed. The proposed methods application
      permitted to exclude entirely the X-rays exposition on the patient. The methods
      are simple and do not need special expenses.

PMID- 9518109
TI  - [Surgical treatment of lymphadenopathy in children].
AB  - Clinical observations of 1365 children with the lymph nodes affection were
      summarized. The diagnosis verification was conducted using the broad arsenal of
      general clinical and special methods of investigation. In complicated situations
      the histochemical and immunogenetic methods were applied for the diagnosis. The
      structure and dynamics of children's morbidity with lymphadenopathies (LAP) was
      studied up, the age, sexual and seasonal peculiarities were systematized, the
      analysis of primary localizations and clinico-morphological comparisons was
      conducted. The basic thesises of the standardized approach were elaborated on the
      ground of the diagnostical and tactical mistakes results analysis.

PMID- 9518110
TI  - [Specific strategies in the treatment of young and middle-age patients with
      spontaneous intracerebral hemorrhage].
AB  - The paper is based on the analysis of 235 young and middle-age patients with non
      traumatic cerebral hemorrhage. Tactics of treatment is determined for each group
      depending on bleeding localization in accordance with World Health Organization's
      classification (1981). Operative treatment is recommended for lateral site of
      hematomas of 25 cm3 and more signs of media structures dislocation of 5 mm and
      more. With the development of hypertension-hydrocephal syndrome surgical
      intervention is directed at its elimination and where possible at hematoma's
      ablation. The amount of operative interventions is limited in case of medial and
      mixed variants of hemorrhages especially when bleedings affect mesencephal
      structures. In conditions of a neurosurgical clinic a pharmacotherapy is used as
      an independent one, as a preparation for surgical treatment as well as during
      operation and in postoperative period.

PMID- 9518111
TI  - [The specifics of diagnosis and surgical treatment of traumatic pneumocephalus].
AB  - Traumatic pneumocefalus (TPC)--complication of severe craniocerebral injury-
      occurs, as a rule, in fractures, line of which is coming across the air
      containing sinuses of the skull base. Depending on the air localization
      subarachnoidal, subdural, epidural, ventricular, clinically asymptomatic and
      strained forms of TPC are discerned. TPC diagnosis is based on taking into
      account the clinico-neurological and radiological examination peculiarities. In
      the acute craniocerebral injury period surgical treatment for parabasal injuries
      is directed on the skull cavity hermetization and for TPC--the valve mechanism
      abolition, liquorous fistula closure, the air tumor emptying and intracranial
      space hermetization. Presence of strained progressing TPC constitutes the life
      perilous indication for surgical intervention.

PMID- 9518112
TI  - [Late complications of the upper cervical vertebral column trauma].
AB  - Two different types of myelopathy course were discerned: myelopathy due to
      instability, occurring early after trauma, rapidly progressing and myelopathy due
      to the long lasting ventral compression of spinal cord at the craniocervical
      level, occurring in several years after trauma, slowly progressing. The
      conduction of occipitocervical spondilodesis using metal loop with the vertebral
      arches fixation in myelopathy due to instability and odontoidectomy in the spinal
      cord ventral compression on craniocervical level constitutes the method of choice
      for the late complications in craniocervical junction trauma.

PMID- 9518113
TI  - [The status of systemic hemodynamics, brain metabolism and blood oxygen transport
      after brain tumor resection under clopheline++ and phentanyl anesthesia].
AB  - The trials were performed on 43 patients at the age from 18 to 73 years, operated
      in connection to brain tumors. The clophelinum--fentanil anesthesia was revealed
      as preventing cerebral metabolism and blood circulatory disorders, brain edema
      development both at the operation and at the early postoperative periods.

PMID- 9518114
TI  - [The use of magnetic resonance tomography in the diagnosis of aneurysm of the
      abdominal aorta].
AB  - The age anatomy of the abdominal aorta (AA) was studied up using magnetic
      resonance tomography (MRT) in 60 patients aging 55-75 years old with diseases of
      vertebral column and spinal cord. The method advantages were established in
      diagnosis of the AA aneurysm in 32 patients, aging 55-74 years, for the thrombi
      detection in aneurysm, for estimation of renal, upper mesenterial and iliac
      arteries, truncus coeliacus state.

PMID- 9518115
TI  - [Reconstructive surgery in atherosclerosis of the femoral-popliteal- tibial
      segment].
AB  - Results of surgical treatment of 368 patients with atherosclerotic occlusions of
      popliteal-tibial segment are analyzed. The operation method choice was based on
      classification, discerning five types of lesion: I type--isolated a. femoris
      superficialis (AFS) occlusion; II type--AFS occlusion, a. femoris profunda
      stenosis; III type--extended occlusions of superficial, popliteal, deep arteries
      and shin arteries; IV type--the lesion of distal part of a. femoris communis and
      a. poplitea; V type--the popliteal artery occlusion with the process transient on
      shin arteries.

PMID- 9518116
TI  - [Ways of decreasing lethality in various forms of bradyarrhythmia].
AB  - Hospital mortality analysis in patients with different kinds of bradyarrhythmias
      after electrocardiopacemaker implantation operation performance was conducted.
      Significant haemodynamics improvement did not occur, if the patients had the
      pronounced coronary atherosclerosis. It was concluded that combined surgical
      correction of this pathology is needed.

PMID- 9518117
TI  - [The ultrasonographic confirmation of the role of external carotid artery in
      blood supply of ischemic lesion in the big cerebral hemisphere].
AB  - Using intraoperative monitoring of the blood flow linear speed in a. cerebralis
      media while total a. carotis interna occlusion in 10 patients the authors have
      concluded, that the degree of blood flow compensation in a. cerebralis media
      depends not only on collateral compensation possibilities by the contralateral
      side and rate of it inclusion, but largely-on a. carotis externa possibility on
      the lesion side.

PMID- 9518118
TI  - [Regional blood circulation and microcirculation in the occlusion of the
      abdominal aorta, iliac and femoral arteries].
AB  - Data on complex examination and surgical treatment of 415 patients with
      occlusions of abdominal aorta, iliac and femoral arteries are adduced. According
      to the stage of ischemia of the extremity tissue three groups of patients were
      determined while making examination-middle degree (II stage of the disease),
      severe (III stage) and extremely severe (IY stage). Positive immediate results of
      treatment were obtained in 402 (96.87%) of patients due to the differential
      approach application in patients examination, taking into account the regional
      blood flow and microcirculation indexes.

PMID- 9518119
TI  - [Humoral immunity in patients with diabetes mellitus and diabetic foot].
AB  - The humoral immunity peculiarities were studied in 40 patients with diabetic foot
      syndrome. Immunoglobulin spectrum changes were analyzed in different types of
      diabetes mellitus.

PMID- 9518121
TI  - [Late postoperative complications of coarctation of aorta].
AB  - Main complications of the remote 2-35 years period after coarctation of the aorta
      repair are studied up. Of 2746 patients 2464 (89.7%) were operated upon at the
      age of 2-25 years old. In 841 (30.61%) of patients were determined coexistent
      heart diseases, more often aortic valve lesion. End-to-end anastomosis was
      fulfilled in 44.6% of operations and patch repair was done in 43.6%. The most
      frequent complication of the remote period was the aortic aneurysm-in 61 (2.2%)
      of cases. It occurred seven times more frequently after the patch repair (4.1%)
      then after anastomosis end-to-end conduction (0.6%). Late postoperative mortality
      equaled 1.5%. The main reasons of it were aneurysms at the site of repair--in 12
      patients, aneurysms of the ascending aorta--in 4 and progressing of the
      coexisting heart diseases--in 10.

PMID- 9518120
TI  - [Surgical treatment of congenital angiodysplasia of the limb].
AB  - Experience of treatment of 189 patients with congenital angiodysplasias of
      extremities is summarized. Following methods of examination have permitted to
      verify the diagnosis: the tissues and venous blood saturation with oxygen
      determination, ultrasonic diagnosis and contrast angiography. Method of choice
      for congenital angiodysplasias treatment is surgical intervention conduction. The
      microsurgical technique application permits to excise angiodysplasias radically
      with simultaneous replacement of the soft tissues defects using the flaps
      autotransplantation on microsurgical anastomoses.

PMID- 9518122
TI  - [Anatomical basis of optimal suturing on the cross-striated skeletal muscle].
AB  - Surgical procedure of the transversely cut skeletal muscle joining, taking into
      account the location of stump and the motor nerve stumps on the cut off, was
      proposed, based on the microsurgical anatomy of the motor nerves fragments of
      skeletal muscles data and on personal experience of the upper extremity large
      segments replantation and musculocutaneous flaps transplantation. The useful
      restoration of the muscle motor activity, estimated clinically and
      instrumentally, was obtained in more than 83% of observations.

PMID- 9518123
TI  - [Ischemic heart disease with the anterior branches of the right coronal artery].
AB  - The coronary arteries shunting was performed in four elderly men with severe
      coronary heart disease, complicated by stagnant heart insufficiency and right
      ventriculus insufficiency (RVI). One patient could not be disconnected from the
      artificial blood circulation (ABC) apparatus till the venous shunting (VS) to
      atherosclerotically strictured right ventriculus anterior branch of right
      coronary artery was not accomplished. Other three patients, to whom VS to this
      branch was already conducted, were disconnected from the ABC without
      complications. In three patients echocardiography trusted RV disorders existence
      before this branch shunting conduction with improvement after shunting. While
      coronary arteries shunting conduction the anastomosis ought to be done to
      anterior branches of RVI when they are affected.

PMID- 9518124
TI  - [The influence of Chernobyl nuclear power station disaster on the erythropoietic
      cells in the microenvironment of the liver].
AB  - Erythropoesis activation, realizing by microenvironmental cells, was noted in
      hepar of the tailless amphibians R. Lessonae and R. Ridibunda, living in the
      Chernobyl AES alienation zone. Destructive changes, and the ribosome-protein
      complexes, fibrillar structures synthesis intensification was revealed in
      hepatocytes. Ribosome-protein complexes and fibrillar-granular material of
      hepatocytes enter the blood stream, where they incorporate into the erythroblasts
      cytoplasm. Focal hyperplasia and macrophages hypertrophy were revealed.
      Macrophages, transporting the hepatocytes cytoplasm components into erythroblasts
      and supplementing them with their cytoplasm synthesis products, take an active
      part in supply of differentiating red blood cells with different materials.

PMID- 9518126
TI  - [Current treatment of postoperative peritonitis].

PMID- 9518125
TI  - [The effectiveness of polymethylsiloxane as a hemosorbent in experiments on
      obstructive jaundice].
AB  - It was established in experiment that the sorption properties of siliconorganic
      sorbent polymethylsiloxan (PMS) dominate significantly over the same of
      haemosorbent SKN-1K concerning common bilirubin level. It is possible to use PMS
      for haemosorption in obturating jaundice, viral hepatitis and in haemoperfusion
      as well.

PMID- 9518127
TI  - [Intracavitary laser therapy in peritonitis].

PMID- 9518128
TI  - [The method of organ-salvaging surgery on the peritoneum for the traumatic
      splenic injury].

PMID- 9518129
TI  - [The laser correlational spectroscopy: a method for the differential diagnosis of
      viral hepatitis and tumoral jaundice].

PMID- 9518130
TI  - [The efficacy of magnetic fields application by internal sorption for the
      treatment of purulent inflammatory diseases in patients with diabetes mellitus].

PMID- 9518131
TI  - [Diagnosis and treatment of chronic colostasis in children].

PMID- 9518132
TI  - [A rare combination of complications of acute necrotizing pancreatitis].

PMID- 9518133
TI  - [Surgical treatment of oblique inguinal hernia].

PMID- 9518134
TI  - [Splenic tumors in children].

PMID- 9518135
TI  - [Perforative duodenal ulcer in children].

PMID- 9518136
TI  - [Surgical treatment of hemolytic hepatitis].

PMID- 9518137
TI  - [Gestational Diabetes. Paris, France, 6 December 1996. Proceedings].

PMID- 9518138
TI  - Maturation of the tract after percutaneous cholecystostomy with regard to the
      access route.
AB  - PURPOSE: To assess the shortest time for catheter removal with regard to the
      transhepatic or transperitoneal approach in patients undergoing percutaneous
      cholecystostomy (PC). METHODS: In this prospective study, 40 consecutive high
      risk patients with acute cholecystitis (calculous, n = 22; acalculous, n = 18)
      underwent PC by means of a transhepatic (n = 20) or transperitoneal (n = 20)
      access route. In 28 patients (70%) computed tomography was used for puncture
      guidance, while in the remaining 12 (30%) the procedures were formed under
      ultrasound control. A fistulography was performed on the 14th postprocedural day
      in al patients and was repeated weekly if the tract was found to be immature. The
      catheter was removed only if a mature tract without evidence of leakage was
      delineated. RESULTS: In 36 of 40 patients the procedure was technically
      successful (90%). Three of the unsuccessful punctures were attempted
      transperitoneally and one transhepatically. Thirty-five of 36 patients showed
      rapid improvement within the first 48 hr following the procedure (96%). Three of
      them died of their severe underlying disease (7.5%) and in another three the
      catheter was accidentally removed prior to the first fistulography (7.5%) A total
      of 30 patients could be fully evaluated after the procedure: 15 with a
      transhepatic, and 15 with a transperitoneal PC. Whereas 14 of 15 patients (93%)
      with transhepatic gallbladder access developed a mature tract after 14 days and
      the remaining patient after 3 weeks, only 2 of 15 patients (13%) with a
      transperitoneal route presented a mature tract after 2 weeks (p < 0.0001; chi2
      test with Yates' correction). Eleven patients (73%) with transperitoneal access
      required 3 weeks and two patients (13%) 4 weeks for complete tract formation.
      CONCLUSION: A period of 2 weeks suffices for the majority of patients to develop
      a mature tract when the transhepatic access route is used; when using the
      transperitoneal route at least 3 weeks are required. We suggest that the
      transhepatic route is preferable since it allows earlier removal of the catheter
      and reduces the incidence of complications and discomfort for the patients.

PMID- 9518139
TI  - Effect of pasteurization and storage on some components of pooled human milk.
AB  - Pooled human milk was subjected to Holder pasteurization and storage at -20
      degrees C up to 90 days and examined for its content of fat and L-lactate and for
      lipid composition. This treatment reduced fats by 6% and L-lactate by at least
      7%. In addition, pasteurization and storage induced triglyceride hydrolysis. The
      absolute amount of free fatty acids (FFAs) which was 0.5% after collection,
      doubled after pasteurization and rose even more after storage. Different FFA
      compositions were found by several authors using the same analytical method even
      for milk samples subjected to the same treatment. More detailed information on
      procedures must be given to explain the different results.

PMID- 9518140
TI  - Simultaneous determination of anabolic and catabolic steroid hormones in meat by
      gas chromatography-mass spectrometry.
AB  - A rapid and economical method for the determination in meat of androgens,
      estrogens, progestogens and corticoids, including some precursors and
      metabolites, has been developed. The extracted steroids are separated in a polar,
      a neutral, and a phenolic fraction by C8-SPE followed by a liquid-liquid
      extraction of the phenolates. Each fraction is separately purified by normal
      phase SPE. The different steroid fractions can be analysed either together to
      obtain a comprehensive hormone pattern in one step or separately to enhance
      detection selectivity and sensitivity. Using a universally applicable silylation
      of the hydroxyl and keto groups, detection limits of 0.02-0.1 microg/kg are
      reached by GC-MS (EI) in the selected ion monitoring mode.

PMID- 9518141
TI  - Characteristics of mass spectrometric analyses coupled to gas chromatography and
      liquid chromatography for 22-oxacalcitriol, a vitamin D3 analog, and related
      compounds.
AB  - The characteristics of the mass spectra of vitamin D3 related compounds were
      investigated by GC-MS and LC-MS using 22-oxacalcitriol (OCT), an analog of 1,25
      dihydroxyvitamin D3, and related compounds. Fragmentation during GC-MS (electron
      impact ionization) of TMS-derivatives of OCT and the postulated metabolites gave
      useful structural information concerning the vitamin D3-skeleton and its side
      chain, especially with respect to the oxidation positions of metabolites. In
      contrast, few fragment ions were observed in LC-MS (atmospheric pressure chemical
      ionization), showing that LC-MS gave poor structural information, except for
      molecular mass. However, when comparing the signal-to-noise ratio (S/N) observed
      during GC-MS and LC-MS analysis for OCT in plasma extracts, the S/N in LC-MS was
      over ten-times greater than in GC-MS, possibly due to the low recovery on
      derivatization and thermal-isomerization in GC-MS. Furthermore, both the GC-MS
      and the LC-MS allowed the analysis of many postulated metabolites in a single
      injection without any prior isolation of target metabolites from biological
      fluids by LC. These results suggest that GC-MS and LC-MS analysis for vitamin D3
      related compounds such as OCT each have unique and distinct advantages.
      Therefore, the complementary use of both techniques enables the rapid and
      detailed characterization of vitamin D3 related compounds.

PMID- 9518142
TI  - Biotransformation of 17-alkyl steroids in the equine: high-performance liquid
      chromatography-mass spectrometric and gas chromatography-mass spectrometric
      analysis of fluoxymesterone metabolites in urine samples.
AB  - In this study the equine metabolism of fluoxymesterone (9alpha-fluoro-11beta
      17beta-dihydroxy-17alpha-meth ylandrost-4-ene-3-one) given orally has been
      investigated. The parent material was not detected, but two major 16-hydroxy
      metabolites which corresponded to a mono- and a di-hydroxylation product were
      evident. One of the hydroxylation positions was identified as C-16. Phase II
      metabolism in the form of glucuronide formation was also common. These steroids
      will provide target compounds for confirming abuse of this drug in the horse.

PMID- 9518143
TI  - Determination of butorphanol in horse race urine by immunoassay and gas
      chromatography-mass spectrometry.
AB  - An analytical procedure to screen butorphanol in horse race urine using ELISA
      kits and its confirmation by GC-MS is described. Urine samples (5 ml) were
      subjected to enzymatic hydrolysis and extracted by solid-phase extraction. The
      residues were then evaporated, derivatized and injected into the GC-MS system.
      The ELISA test (20 microl of sample) was able to detect butorphanol up to 104 h
      after the intramuscular administration of 8 mg of Torbugesic, and the GC-MS
      method detected the drug up to 24 h in FULL SCAN or 31 h in the SIM mode.
      Validation of the GC-MS method in the SIM mode using nalbuphine as internal
      standard included linearity studies (10-250 ng/ml), recovery (+/-100%), intra
      assay (4.1-14.9%) and inter-assay (9.3-45.1%) precision, stability (10 days),
      limit of detection (10 ng/ml) and limit of quantitation (20 ng/ml).

PMID- 9518144
TI  - Determination of N-methylsuccinimide and 2-hydroxy-N-methylsuccinimide in human
      urine and plasma.
AB  - A method for determination of N-methylsuccinimide (MSI) and 2-hydroxy-N
      methylsuccinimide (2-HMSI) in human urine and of MSI in human plasma was
      developed. MSI and 2-HMSI are metabolites of the widely used organic solvent N
      methyl-2-pyrrolidone (NMP). MSI and 2-HMSI were purified from urine and plasma by
      C8 solid-phase extraction and analysed by gas chromatography-mass spectrometry in
      the negative-ion chemical ionisation mode. The intra-day precisions in urine were
      2-6% for MSI (50 and 400 ng/ml) and 3-5% for 2-HMSI (1000 and 8000 ng/ml). For
      MSI in plasma it was 2% (60 and 1200 ng/ml). The between-day precisions in urine
      were 3-4% for MSI (100 and 1000 ng/ml) and 2-4% for 2-HMSI (10,000 and 18,000
      ng/ml) and 3-4% for MSI in plasma (100 and 900 ng/ml). The recoveries from urine
      were 109-117% for MSI (50 and 400 ng/ml) and 81-89% for 2-HMSI (1000 and 8000
      ng/ml). The recovery of MSI from plasma was 91-101% (50 and 500 ng/ml). The
      detection limits for MSI were 3 ng/ml in urine and 1 ng/ml in plasma and that of
      2-HMSI in urine was 200 ng/ml. The method is applicable for analysis of urine and
      plasma samples from workers exposed to NMP.

PMID- 9518145
TI  - Assay of S-ethyl-N-acetyl-l-cysteine in urine by high-performance liquid
      chromatography using post-column reaction detection.
AB  - The assay of the ethyl chloride metabolite S-ethyl-N-acetyl-L-cysteine in human
      urine by HPLC is described. The compound is enriched by adsorption on a non-polar
      adsorbent of graphitized non-porous carbon, and then stripped from positively
      charged compounds by application onto a strong acid cation-exchanger.
      Subsequently, an enzymatic deacetylation is carried out and the acylase is
      removed by centrifugal ultrafiltration. Separation of the sample is performed by
      cation-exchange chromatography applying an eluent of a very low elution strength
      (diluted formic acid). In the column effluent S-ethyl-L-cysteine is derivatized
      by o-phthaldialdehyde and the reaction product is detected by fluorescence
      measurement. In human urine a detection limit in the low ppb range is achieved.

PMID- 9518146
TI  - Determination of gacyclidine enantiomers in human plasma by gas chromatography
      mass spectrometry using selected-ion monitoring.
AB  - A sensitive gas chromatographic assay using mass selective-detection has been
      developed for the simultaneous quantitation of the enantiomers of (+/-)
      gacyclidine (a non competitive N-methyl-D-aspartate antagonist) in human plasma.
      Gacyclidine enantiomers and phencyclidine (PCP), the internal standard, were
      extracted using a single-step liquid-liquid extraction with hexane at pH 8.0.
      Each enantiomer was separated on a chiral gas chromatography capillary column and
      specifically detected by mass spectrometry (MS) in selected-ion monitoring (SIM)
      mode. Gacyclidine enantiomers and PCP were monitored using the fragment ions at
      m/z 206 and 200, respectively. No interference was observed from endogenous
      components. The limit of quantitation (LOQ) for each enantiomer of gacyclidine
      was 300 pg/ml by using plasma samples of 500 microl. The calibration curves were
      linear (r2=0.998) over a range of 0.3125 to 20 ng/ml. The extraction efficiency
      was higher than 95% for both enantiomers. Intra- and inter-day bias were less
      than 10% at every standard curve concentration. Intra-day precision was less than
      19% for (-)-gacyclidine and 15% for (+)-gacyclidine. Inter-day precision was
      below 15% for both enantiomers. The assay was validated for an enantioselective
      pharmacokinetic study in healthy male volunteers.

PMID- 9518148
TI  - Specific gas chromatographic analysis of diethylcarbamazine in human plasma using
      solid-phase extraction.
AB  - Diethylcarbamazine (DEC, 1-diethylcarbamyl-4-methylpiperazine) is an
      antiparasitic piperazine derivative used in the treatment of lymphatic
      filariasis. DEC-N-oxide is a major metabolite in humans which has antifilarial
      activity. Gas chromatographic analysis of DEC in plasma can be complicated by the
      presence of the metabolite, since the thermally unstable DEC-N-oxide is converted
      to a material which coelutes with DEC under the conditions of the analysis. We
      now report a method to separate DEC-N-oxide from DEC in plasma using solid-phase
      extraction with subsequent gas chromatographic analysis using a nitrogen specific
      detector. 1-Diethylcarbamyl-4-ethylpiperazine (E-DEC) was the internal standard.
      The standard curve of DEC is linear in the range of 10 to 200 ng/ml. The limit of
      detection is 4 ng/ml. Reproducibility at 10, 100 and 200 ng/ml concentration
      points of the standard curve gives coefficients of variation of 6.1%, 7.8% and
      1.6%, respectively. Recovery following solid-phase extraction is 99.3% for DEC
      and 94.8% for the internal standard. This sensitive and specific analytical
      method is suitable for pharmacokinetic studies of DEC.

PMID- 9518147
TI  - Rapid, sensitive procedure to determine buspirone levels in rat brains using gas
      chromatography with nitrogen-phosphorus detection.
AB  - Reported here is a rapid, sensitive and relatively inexpensive procedure using
      gas chromatography with nitrogen-phosphorus detection (GC-NPD) to quantify
      buspirone levels in brains of rats. The analyte was directly extracted from brain
      homogenate with toluene after basification and then subjected to GC-NPD analysis
      using a capillary column. The calibration curves were linear over the range of 10
      to 320 ng per 2 ml of brain homogenate, with typical r2 values >0.99. The assay
      was highly reproducible and gave peaks with excellent chromatographic properties.

PMID- 9518149
TI  - Identification of adenine nucleotide-containing metabolites of bisphosphonate
      drugs using ion-pair liquid chromatography-electrospray mass spectrometry.
AB  - Bisphosphonates are synthetic pyrophosphate analogues, which are used as
      therapeutic drugs for the treatment of metabolic bone disorders. Some of these
      bisphosphonates can be metabolised in cells into non-hydrolysable nucleotide
      analogues. In this paper, we describe an ion-pairing high-performance liquid
      chromatography method that is compatible with negative ion electrospray mass
      spectrometry for the separation of these metabolites. Tandem mass spectrometry
      and collision-induced dissociation (CID) were used for identification of the
      metabolites. The CID mass spectra of bisphosphonate-adenine nucleotide adducts
      are very informative, because major fragment ions are formed by cleavage of the
      bisphosphonate moiety from the conjugate. The method was used for detection of
      the nucleotide metabolites of clodronate, tiludronate and etidronate in extracts
      from mammalian cells after treatment with bisphosphonates.

PMID- 9518150
TI  - Sensitive high-performance liquid chromatographic method with fluorometric
      detection for the determination of heparin and heparan sulfate in biological
      samples: application to human urinary heparan sulfate.
AB  - A sensitive high-performance liquid chromatographic method for the determination
      of unsaturated disaccharides produced from heparin and heparan sulfate is
      described. Heparan sulfate was depolymerized using a combination of heparin lyase
      I (EC 4.2.2.7), heparin lyase II and heparin lyase III (EC 4.2.2.8). Seven
      unsaturated disaccharides were separated under isocratic conditions within 25 min
      using acetonitrile-H2O-0.2 M sodium phosphate buffer (pH 7.0)-3.0 M ammonium
      chloride (32:10:1:1) and were monitored by fluorescence detection using 2
      cyanoacetamide as a post-column derivatizing reagent. As little as 2 pmol of a
      disaccharide could be detected with excitation at 346 nm and emission at 410 nm.
      This method was applied to the analysis of normal human urine. It was revealed
      that the concentration of normal human urinary heparan sulfate is 1.53+/-0.36
      mg/mg creatinine (n=4).

PMID- 9518151
TI  - Study of the metabolism of spiramycin in pig liver.
AB  - A major metabolic pathway of spiramycins in pig liver is described. This
      biochemical reaction involves L-cysteine--a common amino acid present in most
      animal tissues--which reacts with the aldehyde function of the antibiotic forming
      a thiazolidine ring. This transformation of spiramycin derivatives drastically
      increased their polarity. A preliminary HPLC method enabling the quantitation of
      each metabolite in the range 0.5 microg/g of liver tissue is proposed. Spiramycin
      S is used as an internal standard while extraction procedures take into account
      the physico-chemical properties of the thiazolidine moieties. By comparison,
      previous HPLC methods underestimated the exact amount of antibiotic residues
      because these metabolites were not extracted from the studied tissues.

PMID- 9518153
TI  - Sensitive chiral high-performance liquid chromatographic assay for labetalol in
      biological fluids.
AB  - The four stereoisomers of the combined alpha- and beta-adrenoceptor antagonist
      labetalol were separated and quantified at therapeutic concentrations by normal
      phase high-pressure liquid chromatography using a chiral stationary phase and
      fluorescence detection. Drug in plasma or urine was recovered by solid-phase
      extraction with 83+/-5% efficiency. Limits of detection from biological samples
      (3 ml) were between 1.5-1.8 ng ml(-1). Intra-day and inter-day variation at 25 ng
      ml(-1) were < or = 2.7% and < or = 5.80% respectively for all stereoisomers. The
      assay was applied to an examination of the disposition of labetalol stereoisomers
      after a single oral dose of racemate to a human volunteer. Labetalol appears to
      undergo enantioselective metabolism leading to relatively low plasma
      concentrations of the pharmacologically active enantiomers.

PMID- 9518152
TI  - Disposition of human drug preparations in the horse. VI. Tiaprofenic acid.
AB  - Urinary and plasma concentrations of the nonsteroidal anti-inflammatory drug
      tiaprofenic acid were determined following oral and intramuscular administration
      of a dose of 1 g to five fasted horses. Quantitation was performed by high
      performance liquid chromatography (HPLC). The limit of quantitation (LOQ) was 0.1
      microg/ml and 0.5 microg/ml in 2 ml plasma and 1 ml urine, respectively. Assay
      precision and extraction recovery were between acceptable values. Tiaprofenic
      acid pharmacokinetics were described by non-compartment analysis of the data.
      Absorption was faster after oral administration as maximum plasma concentrations
      (oral: 6.0+/-3.3 microg/ml; intramuscular: 6.6+/-2.5 microg/ml) were obtained
      after 1 h (oral) compared to 1.6+/-0.4 h (intramuscular) post dosage. Plasma
      binding (66+/-3%) was lower than measured in other species. Tiaprofenic acid was
      detected in urine for at least 24 h. The percentage of the parent drug excreted
      in the first 12 h after oral and intramuscular administration was 38+/-6% and
      34+/-5%, respectively.

PMID- 9518154
TI  - Automated and sensitive method for the determination of formoterol in human
      plasma by high-performance liquid chromatography and electrochemical detection.
AB  - An automated high-performance liquid chromatography (HPLC) method for the
      determination of formoterol in human plasma with improved sensitivity has been
      developed and validated. Formoterol and CGP 47086, the internal standard, were
      extracted from plasma (1 ml) using a cation-exchange solid-phase extraction (SPE)
      cartridge. The compounds were eluted with pH 6 buffer solution-methanol (70:30,
      v/v) and the eluate was further diluted with water. An aliquot of the extract
      solution was injected and analyzed by HPLC. The extraction, dilution, injection
      and chromatographic analysis were combined and automated using the automate
      (ASPEC) system. The chromatographic separations were achieved on a 5 microm,
      Hypersil ODS analytical column (200 mm x 3 mm I.D.), using (pH 6 phosphate
      buffer, 0.035 M + 20 mg/l EDTA)-MeOH-CH3CN (70:25:5, v/v/v) as the mobile phase
      at a flow-rate of 0.4 ml/min. The analytes were detected with electrochemical
      detection at an operating potential of +0.63 V. Intra-day accuracy and precision
      were assessed from the relative recoveries of calibration/quality control plasma
      samples in the concentration range of 7.14 to 238 pmol/l of formoterol base. The
      accuracy over the entire concentration range varied from 81 to 105%, and the
      precision (C.V.) ranged from 3 to 14%. Inter-day accuracy and precision were
      assessed in the concentration range of 11.9 to 238 pmol/l of formoterol base in
      plasma. The accuracy over the entire concentration range varied from 98 to 109%,
      and precision ranged from 8 to 19%. At the limit of quantitation (LOQ) of 11.9
      pmol/l for inter-day measurements, the recovery value was 109% and C.V. was 19%.
      As shown from intra-day accuracy and precision results, favorable conditions (a
      newly used column, a newly washed detector cell and moderate residual cell
      current level) allowed us to reach a LOQ of 7.14 pmol/l of formoterol base (3
      pg/ml of formoterol fumarate dihydrate). Improvement of the limit of detection by
      a factor of about 10 was reached as compared to the previously described methods.
      The method has been applied for quantifying formoterol in plasma after 120 microg
      drug inhalation to volunteers. Formoterol was still measurable at 24 h post
      dosing in most subjects and a slow elimination of formoterol from plasma beyond 6
      8 h after inhalation was demonstrated for the first time thanks to the
      sensitivity of the method.

PMID- 9518155
TI  - Determination of Ro 48-3656 in rat plasma by reversed-phase high-performance
      liquid chromatography. Comparison of 1.5-microm nonporous silica to 3.5-microm
      porous silica analytical columns.
AB  - We describe a method for measuring Ro 48-3656 in EDTA rat plasma by neutral pH,
      reversed-phase high-performance liquid chromatography using a 1.5-microm
      nonporous silica, C18 analytical column and UV absorbance detection to support
      pharmacokinetic studies. We also describe a comparison of the 1.5-microm
      nonporous silica C18 column versus 3.5-microm porous silica C18 columns. The
      final method using the 1.5-microm nonporous silica column demonstrated good
      precision (of both quantification and retention time), accuracy and recovery,
      linearity of dilution and limit of quantification (40 ng/ml Ro 48-3656 using a 20
      microl injection). Samples of neat EDTA rat plasma were prepared by
      ultrafiltration followed by direct injection onto the HPLC column.

PMID- 9518156
TI  - Radioimmunoassay for a novel lignan-related hypocholesterolemic agent, S-8921, in
      human plasma after high-performance liquid chromatography purification and in
      human urine after immunoaffinity extraction.
AB  - The novel compound methyl-1-(3,4-dimethoxyphenyl)-3-(3-ethylvaleryl)-4-hydroxy
      6,7,8- trimethoxy-2-naphthoate (S-8921) has hypocholesterolemic activity in
      animals and is expected to exhibit a similar activity in human. Reversed-phase
      high-performance liquid chromatography (HPLC) separation followed by
      radioimmunoassay (RIA) for human plasma samples (HPLC-RIA) and immunoaffinity
      extraction (IAE) followed by RIA for human urine samples (IAE-RIA) were developed
      for investigation of S-8921 behavior in clinical studies. For the RIA, antisera
      from rabbit and a radioiodine-labelled S-8921 were prepared by immunizing a
      conjugate of S-8921 with bovine serum albumin and by the Bolton and Hunter
      method, respectively. HPLC-RIA using a semi-micro column was very sensitive, that
      is a 0.05 ng/ml limit of quantitation in human plasma, and specific for unchanged
      form of S-8921. IAE-RIA using a centrifugal filtration tube completely eliminated
      the matrix effect of human urine, and was very feasible. The limit of
      quantitation was 0.10 ng/ml. RIA detection following HPLC or IAE proved to be
      very useful for the pharmaceutical analysis of extremely low drug concentrations
      in body fluids.

PMID- 9518158
TI  - Simple high-performance liquid chromatographic column-switching technique for the
      on-line immunoaffinity extraction and analysis of flunitrazepam and its main
      metabolites in urine.
AB  - A sensitive, simple and rapid method without sample pretreatment is presented for
      the simultaneous determination of flunitrazepam and its main metabolites
      (norflunitrazepam, 7-amino- and 7-acetamidoflunitrazepam) in urine. The single
      step procedure is based on a column-switching technique which uses an immobilized
      antibody in an extraction column following concentration on a precolumn and
      separation on an analytical column. UV detection was performed at 254 nm. The
      reusability of the antibody exceeds 88 runs and a complete analysis was performed
      in less than 40 min. The method shows coefficients of variation below 9.9% and
      rates of recovery greater than 92% tested at the level of 50 ng/ml urine. The
      limit of detection was below 2 ng/ml urine for the four compounds.

PMID- 9518157
TI  - Rapid purification and properties of human glycodelin (endometrial alpha2
      globulin).
AB  - The method presented can easily produce milligram amounts of glycodelin from
      pregnancy endometrium, with a 19% yield. It involves anion-exchange
      chromatography, gel permeation and chromatofocusing; it results in one stainable
      band at Mr 28,000 after sodium dodecyl sulphate-polyacrylamide electrophoresis,
      as well as after immunoblot analysis, performed using an affinity-purified IgG
      fraction from an antiserum against glycodelin. In spite of this, the
      corresponding gel isoelectric focusing pattern gives four stainable bands with pI
      values between 4.55 and 5.2. Western immunoblot analysis of tissue extracts
      indicates the presence of glycodelin epitopes associated with materials heavier
      than the native protein. Circular dichroism spectra of the highly purified
      protein in water solutions indicate a large amount of beta-sheet conformation,
      whereas those obtained with different proportions of 2-propanol in water, show an
      increased proportion of alpha-helix conformation.

PMID- 9518159
TI  - Quantification of fluoxetine and norfluoxetine serum levels by reversed-phase
      high-performance liquid chromatography with ultraviolet detection.
AB  - A rapid and sensitive high-performance liquid chromatography assay method was
      developed to determine serum fluoxetine and norfluoxetine levels by single
      extraction of 0.1 ml of serum with sodium hydroxide. The mobile phase (55%
      acetonitrile-45% distilled water containing 10 mM aqueous triethylamine) was used
      to separate fluoxetine and norfluoxetine (25-1000 ng/ml, using clomipramine as
      the internal standard) by ultraviolet detection at 226 nm. The inter- and intra
      day variabilities of fluoxetine and norfluoxetine were 13-18%, and the recoveries
      of both drugs exceeded 89%. This assay method was applied to a pharmacokinetic
      disposition study of fluoxetine in mice.

PMID- 9518160
TI  - Simultaneous determination of methylene violet, halogenated methylene violet and
      their photoproducts in the presence of DNA by high-performance liquid
      chromatography using an internal surface reversed-phase column.
AB  - A simple and rapid isocratic high-performance liquid chromatographic method for
      the analysis of methylene violet, a neutral phenothiazine dye, in the presence of
      DNA has been developed. These chromatographic conditions are also applicable to
      its N-demethylated, bromo and iodo analogs. The method utilizes an internal
      surface reversed-phase column and a mobile phase consisting of 20% acetonitrile
      in 50 mM phosphate buffer (pH 7.0) and detection at 280 nm. Under these
      conditions all five dyes are well resolved from one another and from the faster
      migrating DNA. The effects of organic modifiers, ionic strength and pH of the
      buffer on the capacity factors of the dyes have been investigated. The method has
      successfully been applied to detect the photoproducts of methylene violet and its
      bromo analog in the presence of DNA without removing the biopolymer from the
      reaction mixture.

PMID- 9518161
TI  - Stability-indicating high-performance liquid chromatographic assay of busulfan in
      aqueous and plasma samples.
AB  - A sensitive, specific and stability-indicating high-performance liquid
      chromatographic (HPLC) assay, involving pre-column derivatization and solid-phase
      extraction (SPE), was developed and validated for the quantitation of busulfan
      (BU) in aqueous and plasma samples. The linearity of the assay was in the
      concentration ranges of 0.15-10 microg/ml and 0.15-3 microg/ml for aqueous and
      plasma samples, respectively. The within-day and between-day variations were 2.90
      and 3.31%, respectively, for the aqueous samples, and 9.24 and 14.56%,
      respectively, for the plasma samples. The overall recovery, derivatization yield
      and SPE efficiency of BU from plasma samples were 82.03, 108.01 and 86.69%,
      respectively. Forced degraded samples, either in highly acidic, neutral or basic
      medium, produced no interfering peaks in the chromatogram. The reported assay
      requires only 0.2 ml of plasma for the analysis, and its sensitivity is 150 ng/ml
      by monitoring samples at a wavelength of 254 nm, sufficient to study the plasma
      pharmacokinetics of BU in rats after a clinically relevant oral dose. Moreover,
      the sensitivity of the assay can be significantly increased to 30 ng/ml by
      monitoring samples at a wavelength of 278 nm. The applications of the assay were
      demonstrated with BU solubility measurements in two aqueous systems and with
      plasma samples from a Sprague-Dawley rat for an in vivo pharmacokinetic study. In
      addition, the assay has been employed in the development of a patented
      intravenous formulation, and in evaluations of stability, preclinical
      pharmacokinetics in rats and dogs, and clinical phase I trial of the formulation.
      The assay is readily adaptable to clinical therapeutic drug monitoring.

PMID- 9518162
TI  - Simultaneous determination of O6-benzylguanine and 8-oxo-O6-benzylguanine in
      human plasma by reversed-phase high-performance liquid chromatography.
AB  - A high-performance liquid chromatographic assay for the quantification of O6
      benzylguanine (O6BG) in human plasma was modified to include the metabolite, O6
      benzyl-8-oxo-guanine (8-oxo-O6BG). O6-(p-Chlorobenzyl)guanine was used as the
      internal standard. Plasma samples were extracted with ethyl acetate and
      chromatographed on a C18 base-deactivated reversed-phase column. Separation was
      accomplished by gradient elution with mobile phases consisting of acetonitrile
      and phosphate buffer, pH 3.60. Eluted compounds were observed with diode array
      detection at 288 nm (O6BG) and 292 nm (8-oxo-O6BG). Standard curves were linear
      from 12.5 ng/ml to 1000 ng/ml, with an average regression coefficient of 0.999
      (n=5) for both compounds. The lowest limit of quantitation was 25 ng/ml, with a
      signal-to-noise ratio of 8:1. The within-day relative standard deviations for
      O6BG quality control samples (n=18) with concentrations of 735 ng/ml, 305 ng/ml
      and 38 ng/ml were 2.4%, 4.2% and 5.3%, respectively. The within-day relative
      standard deviations for 8-oxo-O6BG quality control samples (n=18) at
      concentrations of 735 ng/ml, 420 ng/ml and 42 ng/ml were 2.2%, 4.0% and 7.1%,
      respectively. The day-to-day relative standard deviations for the same control
      specimens were 3.1%, 4.8% and 7.1% for O6BG, respectively, and 2.3%, 4.7% and
      11.0% for 8-oxo-O6BG, respectively. This method was applied to plasma samples
      obtained from patients in a clinical trial of O6-benzylguanine. O6-Benzyl-8-oxo
      guanine was identified in patient plasma specimens by liquid chromatography
      electrospray mass spectrometry by comparison with spectral data acquired from
      reference material.

PMID- 9518163
TI  - Determination of naringin and naringenin in human urine by high-performance
      liquid chromatography utilizing solid-phase extraction.
AB  - An HPLC method for determining a flavonoid naringin and its metabolite,
      naringenin, in human urine is presented for application to the pharmacokinetic
      study of naringin. Isocratic reversed-phase HPLC was employed for the
      quantitative analysis by using hesperidin for naringin or hesperetin for
      naringenin as internal standard and solid-phase extraction using a strong anion
      exchanger, Sep-Pak Accell QMA cartridge. The HPLC assay was carried out using an
      Inertsil ODS-2 column (250 x 4.6 mm I.D., 5 microm particle size). The mobile
      phases were acetonitrile-0.1 M ammonium acetate-acetic acid (18:81:1, v/v; pH
      4.7) for naringin and acetonitrile-0.1 M ammonium acetate-triethylamine
      (25:75:0.05; v/v; pH 8.0) for naringenin. The flow-rate was 1.0 ml min(-1). The
      analyses were performed by monitoring the wavelength of maximum UV absorbance at
      282 nm for naringin and at 324 nm for naringenin. The lower limits of
      quantification were ca. 25 ng/ml for naringin and naringenin with R.S.D. less
      than 10%. The lower limits of detection (defined as a signal-to-noise ratio of
      about 3) were approximately 5 ng for naringin and 1 ng for naringenin. A
      preliminary experiment to investigate the urinary excretion of naringin,
      naringenin and naringenin glucuronides after oral administration of 500 mg of
      naringin to a healthy volunteer demonstrated that the present method was suitable
      for determining naringin and naringenin in human urine.

PMID- 9518164
TI  - Determination of ritonavir, a new HIV protease inhibitor, in biological samples
      using reversed-phase high-performance liquid chromatography.
AB  - A simple, accurate and precise high-performance liquid chromatographic method has
      been developed for measurement of ritonavir concentrations in human plasma.
      Ritonavir was partitioned from the plasma using liquid-liquid extraction with a
      mixture of ethyl acetate and hexane at neutral pH, with an average recovery >80%.
      Following two sequential washings of the reconstituted sample with hexane,
      chromatographic separation was accomplished on a C18 analytical column with a
      mobile phase containing acetonitrile, methanol and 0.01 M tetramethylammonium
      perchlorate in 0.1% aqueous trifluoroacetic acid (40:5:55, v/v) with low
      wavelength UV detection at 205 nm. Standard curves were linear (r2>0.9998) over
      the concentration range 0.01-15 microg/ml with both inter- and intra-day
      coefficients of variation typically less than 5%. The stability of ritonavir in
      plasma was excellent, with no evidence of degradation after 5 days at room
      temperature or after 6 months in a freezer. Decontamination procedures for HIV
      positive plasma samples showed 5.6 and 10.2% degradation following heating to 60
      degrees C for 30 or 60 min, respectively.

PMID- 9518165
TI  - Simultaneous analysis of 2-methoxyphenylmetyrapone and its seven potential
      metabolites by high-performance liquid chromatography.
AB  - A sensitive and specific high-performance liquid chromatographic (HPLC) assay has
      been developed for the quantification of 2-methoxyphenylmetyrapone (2-MPMP) and
      its seven potential metabolites in rat urine and whole blood. 2-MPMP, 2
      hydroxyphenylmetyrapone and their N-oxides, together with 2
      methoxyphenylmetyrapol, 2-hydroxyphenylmetyrapol and their N-oxides were
      separated on an Isco Spherisorb ODS-2 reversed-phase column (250 x 4.6 mm, I.D.,
      5 microm), with an Isco Spherisorb ODS-2 guard cartridge (10 x 4.6 mm I.D.). A
      gradient elution was employed using solvent system A (acetonitrile-water
      triethylamine-acetic acid, 27.3:69.1:0.9:2.7%, v/v) and solvent system B
      (methanol), the gradient program being as follows: initial 0-4 min A:B=74:26; 4
      10 min linear change to A:B=50:50; 10-16 min maintain A:B=50:50; 16 min return to
      initial conditions (A:B=74:26). Flow-rate was maintained at 1.25 ml/min, and the
      eluent monitored using a diode array multiple wavelength UV detector set at 260
      nm. Most of the analytes were baseline resolved, and analysis of samples
      recovered from blood or urine (pH 12, 3 x 5 ml of dichloromethane, recovery
      approximately 20-95%) revealed no interference from any co-extracted endogenous
      compounds in the biological matrices, except for 2-hydroxyphenylmetyrapol N-oxide
      (2-OHPMPOL-NO) at low concentrations. The calibrations (n=6) were linear (r > or
      = 0.996) for all analytes (approximately 0.5-100 microg/ml), with acceptable
      inter- and intra-day variability. Subsequent validation of the assay revealed
      acceptable precision, as measured by coefficient of variation (C.V.) at the low
      (0.5 mg/ml), medium (50 microg/ml) and high (100 microg/ml) concentrations. The
      limits of detection for 2-MPMP and their available potential metabolites, except
      2-OHPMPOL-NO, in rat urine and blood were both 0.5 microg/ml, respectively.

PMID- 9518166
TI  - High-performance liquid chromatographic determination of seratrodast and its
      metabolites in human serum and urine.
AB  - A high-performance liquid chromatographic (HPLC) method was developed for the
      simultaneous determination of seratrodast, a new antiasthmatic drug, and its
      metabolites (M-I to M-III) in human serum and urine. The method for serum and
      urine with and without enzymatic hydrolysis using beta-glucuronidase involved
      liquid-liquid extraction and chemical oxidation with iron(III) chloride. The
      compounds in the extract were analyzed using HPLC with UV detection at 266 nm.
      The detection limits of seratrodast, M-I, M-II and M-III in serum and urine were
      5-10 and 5-20 ng/ml, respectively, and those of deconjugated compounds in urine
      were 10-50 ng/ml. The method was applicable for human serum and urine from
      clinical trials.

PMID- 9518167
TI  - Development of a capillary electrophoretic method for the separation of the
      macrolide antibiotics, erythromycin, josamycin and oleandomycin.
AB  - Capillary electrophoresis (CE) provides high separation efficiency and thus is
      suitable for the analysis of complex mixtures of structurally similar compounds.
      The versatile nature of CE can be realised by controlling the chemistry of the
      inner capillary wall, by modifying the electrolyte composition and by altering
      the physicochemical properties of the analyte. A CE method has been developed for
      the separation of three macrolide antibiotics, erythromycin, oleandomycin and
      josamycin. A systematic approach was used to maximise analyte differential
      electrophoretic mobility by manipulating electrolyte pH, molarity and
      composition. In addition, some instrumental parameters such as capillary length
      and diameter and applied voltage were varied. The effect of the sample solvent
      and on-capillary concentrating techniques such as field amplified sample
      injection were investigated. Also, the influence of the injection of a water plug
      on the quantity of sample injected was demonstrated. The macrolides were
      completely resolved in less than 30 min in a 100 cm x 75 microm I.D. fused-silica
      uncoated capillary with a Z-shaped flow cell of path-length 3 mm. The analysis
      was performed in a 75 mM phosphate buffer (pH 7.5) with 50% (v/v) methanol and an
      applied voltage of 25 kV was selected to effect the separation.

PMID- 9518168
TI  - Determination of erythromycin and related substances by capillary
      electrophoresis.
AB  - Current compendial methods of assay for the analysis of erythromycin and its
      related substances involve the use of microbiological techniques. These
      techniques are non-selective and tedious, thus there is a need for the
      development of highly specific, quantitative analytical methods. Erythromycin was
      analysed in a 50 mM phosphate buffer (pH 7.5) and run at an applied voltage of 20
      kV. Detection sensitivity was enhanced by using a wavelength of 200 nm and
      selecting an injection solvent of lower conductivity than the electrolyte:
      acetonitrile-water (20:80, v/v). In order to facilitate the separation of
      erythromycin and its related substances, the organic solvent ethanol (35%, v/v)
      was incorporated into a modified 150 mM phosphate buffer (pH 7.5) and run at an
      applied voltage of 30 kV. Resolution of all the compounds was achieved in
      approximately 45 min. The methods described are accurate and precise and thus
      suitable for the quantitative determination of erythromycin and the related
      substances, erythromycin C, anhydroerythromycin and N-demethylerythromycin A.

PMID- 9518169
TI  - Comparative analysis of conjugated bile acids in human serum using high
      performance liquid chromatography and capillary electrophoresis.
AB  - This paper describes the analysis of conjugated bile acids in human serum using
      reversed-phase high-performance liquid chromatography (HPLC) and micellar
      electrokinetic capillary electrophoresis (CE). Samples of healthy subjects and
      patients with different hepatic diseases were pretreated with a simple
      preparation procedure using a solid-phase extraction technique. The optimal
      analytical conditions of both chromatographic methods were investigated for the
      convenience and reliability for routine analysis. Both HPLC and CE methods were
      found to be reliable and compatible. The recoveries of nine bile acid conjugates
      using both methods were generally >85% and reproducibility >90%. The day-to-day
      variation of retention time was <5% for HPLC, while the variation of migration
      time for CE was <3%. Although the detection limit of the HPLC method (1 nmol/ml)
      was five times more sensitive than that of the CE method, the CE method was
      considered to be more time and cost effective.

PMID- 9518170
TI  - Determination of serotonin, catecholamines and their metabolites by direct
      injection of supernatants from chicken brain tissue homogenate using liquid
      chromatography with electrochemical detection.
AB  - An isocratic liquid chromatographic method with electrochemical detection for the
      determination of L-3,4-dihydroxyphenylalanine, dopamine, norepinephrine,
      epinephrine, serotonin, and their major metabolites, 3,4-dihydroxyphenylacetic
      acid, 4-hydroxy-3-methoxyphenylacetic acid and 5-hydroxyindole-3-acetic acid in
      chicken brain tissue is described. Chickens were killed at different ages, the
      brains were quickly frozen and 300-microm cryostat sections were made. From these
      sections, two to six tissue micropunches (1 mm in diameter) were punched out from
      20 different areas of the hypothalamus and homogenated in 100 microl 0.1 M
      perchloric acid which included 0.01% cysteine as antioxidant. Fifty-microl
      supernatants were injected directly onto the LC system, separated on a 3-microm
      Phase II ODS column (100 x 3.2 mm I.D.) and detected by an electrochemical
      detector at a potential of +0.75 V. Standard curves, recoveries, analytical
      precision and detection limits were investigated for each monoamine
      neurotransmitter and its metabolites. The method was applied to study the
      influence of food restriction on the concentration of monoamine neurotransmitters
      in different brain areas, known to be involved in feeding and reproductive
      behaviour of female broiler chickens. Over 1000 micropunched tissue samples from
      ad libitum fed and food-restricted female broiler chickens were analyzed. Our
      results provide a possible role for catecholamines and indolamines in the altered
      feeding and reproductive behaviour of the broiler chicken.

PMID- 9518171
TI  - Rapid determination of p-aminohippuric acid in serum and urine by high
      performance liquid chromatography.
AB  - We report a simple and rapid HPLC procedure for measuring p-aminohippuric acid in
      serum and urine. After deproteinization with acetonitrile and addition of p
      aminobenzoic acid as an internal standard, the chromatographic run is performed
      on a C18 column with the absorbance detector set at 275 nm. The separation is
      carried out in 10 min at a flow-rate of 1.0 ml/min with a mobile phase composed
      of 7 mmol/l 1-decanesulfonic acid, pH 3.70, and acetonitrile (82:18, v/v). The
      relationship between p-aminohippuric acid concentration and the p-aminohippuric
      acid/internal standard peak area is linear up to 100 microg/ml. Within-run
      precision measured at three different p-aminohippuric acid concentrations ranges
      from 1.73 to 1.98% in serum and from 0.72 to 1.32% in urine. Between-run
      precision varies from 1.80 to 4.06% in serum and from 1.05 to 2.66% in urine.
      Analytical recovery is between 98.26 and 99.44% in serum and from 99.57 to
      100.45% in urine. The method is very simple, sensitive, and requires small
      volumes of sample for the assay (100 microl). Therefore, it could be a useful
      tool for the analysis of p-aminohippuric acid in the evaluation of renal plasma
      flow.

PMID- 9518172
TI  - Headspace gas chromatography with capillary column for urine alcohol
      determination.
AB  - A headspace gas chromatographic method using a fused-silica capillary column
      Poraplot Q has been developed and validated for the detection and quantification
      of ethanol in urine. Under optimized conditions, ethanol was properly separated
      from acetaldehyde, acetone, isopropanol, methanol and n-propanol. Limits of
      detection (LODs) and quantification (LOQs) were 0.008 and 0.010 g/l,
      respectively. The precision studies within-run and between-run, using spiked
      urine samples (0.08, 0.8 and 2.0 g/l) showed maximum coefficients of variation
      5.9 and 6.5%, respectively. Results of ethanol recovery varied from 91.6+/-0.8 to
      103.3+/-1.8% over the concentration range from 0.01 to 3.20 g/l. The method was
      appropriate for the detection of ethanol in urine samples. This matrix can be
      used for monitoring alcohol abuse in the workplace and used in alcohol
      rehabilitation programs.

PMID- 9518174
TI  - Simple high-performance liquid chromatographic method for determination of
      losartan and E-3174 metabolite in human plasma, urine and dialysate.
AB  - A simple high-performance liquid chromatographic (HPLC) method was developed for
      the determination of losartan and its E-3174 metabolite in human plasma, urine
      and dialysate. For plasma, a gradient mobile phase consisting of 25 mM potassium
      phosphate and acetonitrile pH 2.2 was used with a phenyl analytical column and
      fluorescence detection. For urine and dialysate, an isocratic mobile phase
      consisting of 25 mM potassium phosphate and acetonitrile (60:40, v/v) pH 2.2 was
      used. The method demonstrated linearity from 10 to 1000 ng/ml with a detection
      limit of 1 ng/ml for losartan and E-3174 using 10 microl of prepared plasma,
      urine or dialysate. The method was utilized in a study evaluating the
      pharmacokinetic and pharmacodynamic effects of losartan in patients with kidney
      failure undergoing continuous ambulatory peritoneal dialysis (CAPD).

PMID- 9518173
TI  - Application of high-performance thin-layer chromatography for the detection of
      organophosphorus insecticides in human serum after acute poisoning.
AB  - We developed a rapid and simple method for identifying 25 commonly used
      organophosphorus insecticides in human serum using high-performance thin-layer
      chromatography (HPTLC). These organophosphates were separated on plates with
      three different developing systems within 6-18 min and detected by means of
      ultraviolet radiation and coloring reactions with 4-(4-nitrobenzyl)pyridine
      tetraethylenepentamine reagent (NT reagent) or palladium chloride reagent (PdCl2
      reagent). Each organophosphate was accurately identified by means of the R(F) x
      100 value and the spot color in three systems. The detection limits of
      dichlorvos, fenitrothion, malathion, methidathion, parathion and trichlorfon in
      serum by the liquid-liquid extraction method were 1.1, 0.12, 0.12, 0.05, 0.6 and
      0.1 microg/ml, respectively. These sensitivities may be sufficient to detect
      those organophosphates in patient serum after acute poisoning.

PMID- 9518175
TI  - Simple method for the quantitation of mycophenolic acid in human plasma.
AB  - A simple and rapid isocratic reversed-phase high-performance liquid
      chromatographic method using UV detection was developed for the quantitation of
      mycophenolic acid (MPA) in human plasma. The assay was sufficiently robust to
      allow the analysis of up to 100 samples in a single analytical run.

PMID- 9518176
TI  - Monitoring of met-enkephalin in vivo with 5-min temporal resolution using
      microdialysis sampling and capillary liquid chromatography with electrochemical
      detection.
AB  - A method based on microdialysis sampling and capillary liquid chromatography with
      electrochemical detection that allows in vivo monitoring of met-enkephalin with 5
      min temporal resolution is described. Sampling was achieved using a concentric
      microdialysis probe made from polycarbonate membrane material with a 20 kDa cut
      off. This probe had an in vitro relative recovery for met-enkephalin of 63% at a
      dialysis flow-rate of 0.6 microl/min. Separations were performed using 7 cm x 25
      microm I.D. fused-silica capillary columns packed with 5 microm Alltima C18
      particles. A carbon fiber microelectrode was used as the detector electrode. The
      mass detection limit for met-enkephalin with this system was 40 amol. With on
      column preconcentration, up to 2 microl of sample could be loaded onto the column
      resulting in concentration detection limits as low as 20 pM for met-enkephalin.
      Direct injection of dialysate, collected at 5-min intervals, allowed
      determination of met-enkephalin concentrations in the rat globus pallidus under
      basal and K+-induced depolarization conditions.

PMID- 9518177
TI  - Evaluation of liquid chromatographic behavior of restricted-access media
      precolumns in the course of direct injection of large volumes of plasma samples
      in column-switching systems.
AB  - The chromatographic behavior of an alkyl-diol silica (ADS, 25 x 4 mm I.D.) and a
      semipermeable surface (SPS, 10 x 10 mm I.D.) supports two types of restricted
      access media (RAM), which served as precolumns in column-switching systems for
      direct injection of large volumes of plasma samples (500 microl), was studied
      with regard to peak performance, retention and column back pressure. The
      adsorption of matrix proteins both on sealings (porous frits and sieves) and
      packings was also examined. Columns of ADS and SPS were unchanged after the
      injection of 10-20 ml human plasma under normal working conditions. Even when
      changes occurred on the precolumns (>50 ml of plasma in total), it was still
      possible to regenerate the column performance by replacing the column sieves, or
      by washing and removing columns from the system for a period, since the changes
      were more related to the blockage of sealings and/or the adsorption of proteins
      on the hydrophilic surfaces. Proteins could eventually be unspecifically adsorbed
      on the hydrophobic ligand of the support. It was found on one ADS column that the
      retention decreased by 20% and the pressure increased 30 bar after an intensive
      loading of 75 ml plasma (injection volume, 500 microl) without reconditioning
      procedure. Studies showed that the column sealings played the most important role
      for the lifetime of RAM columns. For ADS columns, using sieves without
      polytetrafluoroethylene (PTFE) nets were the best. No significant difference in
      column life span between SPS and ADS was found.

PMID- 9518178
TI  - Separation of paraproteins from human plasma by membrane chromatography.
AB  - Membrane chromatography using a commercially available blotting membrane was
      performed in a dead-end filtration mode to separate paraproteins from plasma of
      patients suffering from paraproteinemia. The affinity membrane was found to
      display distinct specificity to monoclonal IgG1. A dissociation constant (Kd) of
      3.2 microM and a maximum binding capacity of 1.43 mg/cm2 IgG1 paraprotein were
      obtained from the adsorption isotherm of the affinity membrane. The membrane was
      found to absorb immunoglobulins species-dependently because no binding of
      immunoglobulins from mouse, rat and rabbit could be observed.

PMID- 9518179
TI  - Isolation and purification of two major serum amyloid A isotypes SAA1 and SAA2
      from the acute phase plasma of mice.
AB  - A new procedure was developed for isolation of two major serum amyloid A (SAA)
      isotypes SAA1 and SAA2 from acute-phase plasma of mice. The procedure included
      preparation of high-density lipoproteins (HDLs) and their separation by sodium
      dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). The SAA proteins
      (Mr 12,000) were electroeluted and afterwards purified from SDS by gel permeation
      chromatography on a Fractogel TSK-40F column in aqueous 50% acetonitrile-0.1%
      TFA. Finally, the SAA proteins free from SDS were fractionated by high
      performance liquid chromatography on a Vydac 214TP54 column (250 x 4.6 mm I.D.,
      particle size 5 microm), yielding two major fractions with k=5.2 and k=5.5. The N
      and C-terminal sequence analyses and mass spectrometry demonstrated the purity
      of these two major fractions and their identity with apo SAA1 (k=5.2) and apo
      SAA2 (k=5.5). The developed procedure is applicable to small amounts of pooled
      murine plasma (6-7 ml) and could be readily modified from small to large scale
      preparations.

PMID- 9518180
TI  - Simple and rapid method for determining nicotinamide adenine dinucleotide
      synthetase activity by high-performance liquid chromatography.
AB  - A method is described for the determination of nicotinamide adenine dinucleotide
      synthetase (NADS) activity in human blood. Using high-performance liquid
      chromatography (HPLC), the formed NAD is separated from the substrates and the
      other blood components in less than 13 min. The activity of NADS determined by
      HPLC is closely correlated with that determined by the conventional
      spectrophotometric method, which requires two steps of enzyme reaction. The
      present method is simple and reliable and facilitates the routine analysis of
      NADS activity.

PMID- 9518181
TI  - Simultaneous determination of cysteine sulfinic acid and hypotaurine in rat
      tissues by column-switching high-performance liquid chromatography with
      electrochemical detection.
AB  - Cysteine sulfinic acid (CSA) and hypotaurine (HT) were determined by
      electrochemical detection with a glassy carbon electrode at 0.95 V vs. Ag/AgCl.
      The separation of CSA and HT was accomplished by coupled-column liquid
      chromatography, consisting of an anion-exchange column and a cation-exchange
      column. For the determination of CSA and HT in rat tissues, a column-switching
      system was introduced to remove interferences from late-eluting endogenous
      substances. The limits of determination were 0.05 microM for both sulfinic acids.
      The average precisions (C.V.) over the concentration range of 0.05 to 5 microM
      were 4.3% for CSA and 4.2% for HT.

PMID- 9518182
TI  - Simultaneous measurement of allantoin, uric acid, xanthine and hypoxanthine in
      blood by high-performance liquid chromatography.
AB  - A high-performance liquid chromatographic method for determining catabolism
      products of nucleic acids and purines, such as oxypurines (i.e. uric acid,
      xanthine and hypoxanthine) and allantoin in the blood plasma of ruminants was
      developed. The plasma was deproteinized with 10% trichloroacetic acid. The method
      enabled determination of oxypurines without derivatization. Allantoin was
      determined after conversion with 2,4-dinitrophenylhydrazine to a hydrazone (GLX
      DNPH). Separation of converted allantoin, uric acid, xanthine and hypoxanthine
      derivatives was carried out using two reversed-phase C18 columns. The combination
      of pre-column derivatization and gradient elution with monitoring of the effluent
      at 205, 254 and 360 nm provides a simple and selective analytical tool for
      studying oxypurines and allantoin in plasma. The total run time of the HPLC
      analysis was 60 min. The recovery of the purine derivatives (i.e. oxypurines and
      allantoin) added to the plasma was between 95 and 106%. Purine derivatives were
      stable when the processed samples were stored for 7 days at -10 degrees C. The
      low values of the intra-assay coefficient of variations (2.5-4.6%) and the low
      values of the detection limits (0.187-0.004 nmol) point to the satisfactory
      precision and sensitivity of the method.

PMID- 9518183
TI  - Alteration of acidic lipids in human sera during the course of pregnancy:
      characteristic increase in the concentration of cholesterol sulfate.
AB  - In this study, we determined the concentrations of acidic lipids, including
      cholesterol sulfate (CS), sulfatide and GM3 ganglioside, in human sera of non
      pregnant state and during the course of pregnancy. In human sera of non-pregnant
      women, GM3 was present at a concentration of 8 nmol/ml and the concentrations of
      CS and sulfatides were less than 20% of that of GM3. The concentration of
      sulfatides in sera at the second trimester of gestation was decreased, but CS
      gradually increased from the first to the third trimester of gestation with a
      correlation coefficient of 0.66, and a correlation between the concentration of
      CS and weeks of gestation (p<0.01). CS was also contained in the placental villi,
      and its concentration increased from the first to the third trimester of
      gestation, suggesting that placental CS is one of the source of CS in the blood
      by shedding.

PMID- 9518184
TI  - C3 mesangial proliferative glomerulonephritis--an evaluation of acute
      poststreptococcal glomerulonephritis?

PMID- 9518185
TI  - [The continuing education seminars of the Professional Society of German
      Surgeons, Inc. as preparation for the specialist test. Surgery and its main
      fields].

PMID- 9518186
TI  - [Changes due to the 2nd reorganization law. What has changed for contract
      physicians since 1 July 1997?].

PMID- 9518188
TI  - [The notice of treatment contracts with insurance plan hospitals. Legal
      protection, strategies, consequences, experiences].

PMID- 9518187
TI  - [The physician on the Internet].

PMID- 9518189
TI  - [The consequences of drug budgeting].

PMID- 9518190
TI  - [The inclusion of data documentation in the endoprosthesis registry. An effective
      instrument for quality assurance in endoprosthetics].

PMID- 9518191
TI  - [5000 Germans catch hepatitis C annually. The Robert Koch Institute points to an
      alarming medical and health politics problem].

PMID- 9518192
TI  - [The covered medical treatment of privately insured self-payers].

PMID- 9518193
TI  - [The epidemiology of multiple trauma].
AB  - Trauma is the leading cause of death for people up to 40 years of age in Germany.
      Most of the patients were injured in traffic accidents where special injury
      patterns could be detected: head injuries in bicycle and pedestrian accidents,
      lower extremity injuries in motorcycle accidents, and chest and pelvis injuries
      in car accidents. After falls from a height, the most common injuries were
      fractures of the thoracic and lumbar spine. The treatment of polytrauma patients
      requires high health care resources and demands sophisticated medical support. It
      is estimated that every trauma patient costs daily approximately DM 4,700. It is
      not only the acute medical care that burdens our social system, but also the long
      period of rehabilitation and reintegration. The number of preventable trauma
      deaths can be significantly reduced in special trauma centers, and the high costs
      could be damaging for smaller hospitals. A plea is made for more preventive
      measures and legislative changes to reduce the number of traffic accidents. The
      medical care of trauma patients should be in special trauma centers.

PMID- 9518194
TI  - [The classification of the severely and multiply injured--what has been
      established?].
AB  - Among the numerous scores available for the quantitative evaluation of injury
      severity, only few have proved themselves effective in clinical practice. The
      "Revised Trauma Score"--based on physiological variables--is the most widespread
      in preclinical use. The "Injury Severity Score"--based on anatomical data--is the
      most accepted for defined indices. However, a combination of the two, known as
      the "Trauma and Injury Severity Score (TRISS)", represents an international
      standard for quality control. Recent experience with TRISS in central Europe has
      shown that an increasing number of patients cannot be registered due to missing
      data. One reason for this is the intense preclinical treatment and its influence
      on physiological variables. The practicability of this method for quality control
      -combined with additional efforts--must be questioned in Germany. A score system
      based, for example, on the obligatory score of the "International Classification
      of Diseases", might be a good alternative with less effort required for each
      patient. Further investigations are necessary, however, before any final
      decisions are made.

PMID- 9518195
TI  - [Immunology in the severely injured].
AB  - Immunological complications frequently occur during the clinical course in
      patients with multiple injuries. The increased release of pro-inflammatory
      mediators during the immunological response to trauma may lead to the systemic
      inflammatory response syndrome (SIRS) and furthermore, to multisystem organ
      failure (MOF), which is associated with a mortality of up to 80%. The development
      of multiple organ failure following major trauma is associated with remote organ
      failure, the dysfunction of organs which were not initially affected by the
      trauma. This manuscript reviews recent data in experimental trauma research and
      offers a more detailed evaluation of the immunological findings in trauma
      patients. In particular, the role of pro- and anti-inflammatory cytokines in the
      development or SIRS, MOF and ROF is discussed. Despite the enormous progress in
      clinical immunology and the available data on trauma-induced immune dysfunction,
      a large number of questions still remain to be answered before the immunological
      alterations following severe trauma can be beneficially influenced by
      immunomodulatory therapeutic efforts.

PMID- 9518196
TI  - [New diagnostic strategies in multiple injury].
AB  - The diagnostic strategies in multiple trauma aim at rapid identification of life
      threatening injuries, recognition of serious organ lesions, and evaluation of the
      systemic trauma impact, as well as the resulting host reaction. Besides
      improvements in the structure and organization, major innovations in imaging
      techniques have significantly improved and accelerated evaluation of the patient
      with multiple injuries in the emergency room. Systematic diagnostic work-up,
      integrated multidisciplinary approach, and defined algorithms for traumatic key
      symptoms represent the hallmarks of successful emergency room management. In
      particular, diagnostic work-up of injured body cavities using sonography and
      helical computed tomography are evaluated.

PMID- 9518197
TI  - [Minimally invasive ventral spondylodesis in injuries to the thoracic and lumbar
      spine].
AB  - Thirty-eight patients with 40 fractures of the thoracic spine and the
      thoracolumbar junction were treated by a minimally invasive procedure, which
      includes partial corporectomy, the interposition of a tricortical bone graft and
      anterior stabilization by plate spondylodesis under thoracoscopic control. For 36
      patients the operation was successfully performed in a complete thoracoscopic
      way; in 2 patients conversion to an open technique was necessary. Two
      postoperative complications such as a reversible lesion of the thoracodorsalis
      nerve and a transient irritation of nerve root L1 on the approach side were
      encountered. Postoperative control by X-ray and CT scan showed correct
      positioning of the bone graft, as well as the fixation device in all patients.
      Our experience with this minimally invasive stabilizing procedure for injuries of
      the thoracic spine and the thoracolumbar junction demonstrated the feasibility of
      the method. Compared to the open method the benefit of minimally invasive surgery
      included postoperative pain reduction, shorter hospitalization, early recovery of
      function and reduced morbidity of the operative approach.

PMID- 9518198
TI  - [Arthroscopic surgical measures in the shoulder joint].
AB  - Arthroscopic and open surgery have to be combined for successful surgical therapy
      of the shoulder joint. A surgeon performing open surgery alone or just using
      arthroscopic measures cannot cover the full spectrum of modern shoulder surgery.
      Isolated diagnostic arthroscopy is rarely indicated. Far more common, diagnostic
      arthroscopy is combined with an operative procedure both to confirm preoperative
      assessment of pathology and to uncover associated lesions. The results of
      arthroscopic stabilization of chronic anterior post-traumatic dislocations fail
      to compare with the high success rates of open procedures. Better patient
      selection will probably be the key to improving results. In cases of acute
      traumatic first-time dislocation in young, highly athletic people, arthroscopic
      repair of the isolated Bankart-Perthes lesion offers the attractive advantage of
      anatomic reconstruction with minimal soft-tissue dissection. Further indications
      for arthroscopic measurements of pathologies of the glenohumeral joint are
      synovectomy in rheumatoid arthritis, capsulotomy in frozen shoulder and tenodesis
      for lesions of the long head of the biceps. Arthroscopic subacromial
      decompression according to Ellman is the procedure performed most often and most
      successfully in the shoulder joint and has overcome the classic Neer open
      acromioplasty. For smaller tears of the supraspinatus tendon, arthroscopic
      acromioplasty can be combined with an all arthroscopic suture repair or with mini
      open repair. Larger tears of the rotator cuff are still the domain for open
      reconstructive procedures. In associated or isolated AC joint arthritis, an
      arthroscopic Mumford procedure can be performed. For chronic calcific tendinitis,
      isolated arthroscopic excision of the calcium deposit is of great value.
      Additionally, acromioplasty is needed for true mechanical obstruction of the
      subacromial space.

PMID- 9518199
TI  - [The potentials of minimally invasive surgical measures in the knee joint].
AB  - The treatment of knee joint injuries has seen marked development in the last few
      years. The surgical trauma of intra-articular fracture reconstruction has been
      reduced significantly. Retrograde nailing, percutaneous plating and specific
      exposures to distal femur and proximal tibia fractures have been established.
      Percutaneous osteosynthesis controlled by arthroscopy or fluoroscopy is widely
      used for B-fractures of the tibial plateau. Injectable bone mineral cement adds
      to reduced trauma of surgical treatment of these fractures. In all knee ligament
      procedures, arthroscopy is obligatory for diagnosing and conducting meniscus
      surgery. Ligament reconstruction should be performed either arthroscopically or
      by a limited arthrotomy, the results being comparable at present.

PMID- 9518200
TI  - [The differential indication for "open" or "endoscopic" carpal tunnel release].
AB  - Carpal tunnel syndrome is one of the most common nerve compression syndromes.
      Nocturnal paresthesia and pain are early symptoms, and hypesthesia and thenar
      atrophy are late symptoms. These days endoscopic and open operation techniques
      are available. Minimal trauma after endoscopic release allows early return to
      work. The endoscopic technique should be performed by experienced surgeons to
      avoid severe complications.

PMID- 9518201
TI  - [Phospholipase A2--from basic research to clinical reality].
AB  - Phospholipase A2 (PLA2) is a group of secretory as well as intracellular enzymes
      that release phospholipids as an early step in inflammation and play a
      physiologic role in digestion. In humans, the group of secretory, low-molecular
      weight PLA2 (sPLA2) is differentiated from the cytosolic, high-molecular-weight
      PLA2 (cPLA2). The two known cPLA2 mediate the intracellular response to
      inflammation by releasing arachidonic acid from membrane phospholipids. Secretory
      pancreatic PLA2 (sPLA2-I) is a digestive zymogen secreted from pancreatic acinar
      cells in its inactive form. Activated by trypsin in the duodenum, it is an
      important digestive enzyme. In acute pancreatitis, circulating sPLA2-I indicates
      pancreatic injury but is mostly inactive. Synovial-type secretory PLA2 (sPLA2
      II), first isolated from synovial fluid of arthritis patients, is increased in
      inflammation, after surgery or trauma, and in various inflammatory diseases.
      Unlike sPLA2-I, its catalytic activity is held responsible for mediating the
      systemic inflammatory reaction and its complications by regulating the synthesis
      of prostaglandins, leukotrienes and platelet activating factor. Clinically, sPLA2
      II offers new possibilities as an early marker for severe inflammation and
      predicting systemic complications in severely ill patients.

PMID- 9518202
TI  - [Carbon-fiber implants for knee ligament reconstruction. 10-year results].
AB  - The retrospective results of carbon prostheses for knee ligament reconstruction
      in 120 patients, as established by questionnaire, are reported at 10 +/- 2 years
      follow-up. Eighty patients could also be reviewed clinically. Some 60% of the
      patients showed good subjective function at reduced activity level. Complications
      were seen in 72.5% of the patients with rupture of the carbon prosthesis and in
      68% of those with synovitis. X-ray showed osteoarthritis in up to 59% of the
      patients. Carbon prostheses for collateral ligament reconstruction (85% medial,
      5.8% lateral) were successful in 75% of cases. Activity and time seem to be less
      responsible for failure of the carbon prostheses than the features of growing in.
      Destruction of the knee joint over time is due to reactive synovitis and
      catabolic enzyme reaction and correlates with joint effusion and pain. If these
      problems appear, (arthroscopic) resection of the synovia is indicated to
      interrupt the circulus vitiosus.

PMID- 9518203
TI  - [Functional fracture treatment of the forearm. The indications and results].
AB  - In a retrospective study from 1986 to 1995, 64 forearm fractures were treated
      with brace. Clinical and roentgenographic follow-up data were available for 49
      patients (76.6%). There were 49.0% ulna shaft, 38.9% radius and 12.2% forearm
      fractures. The average time to healing was 10.2 weeks. Functional results were
      excellent in 57.1%, good in 34.7% and poor in 8.2% of cases. Two (4.1%) fractures
      (radius, forearm shaft) were not considered as healed and were re-operated with
      plate osteosynthesis. The ideal indication for fracture bracing is ulna shaft
      fracture. Radius and forearm shaft fractures can also be treated, but patients
      must be informed about the long time to healing and operative alternatives.

PMID- 9518204
TI  - [The conservative and surgical therapy of traumatic humeral shaft fractures].
AB  - Sixty-three patients with humeral shaft fractures were evaluated clinically and
      radiographically 18 months after injury; 27 patients were treated surgically
      (group A) and 36 patients conservatively (group B). Analysis of the results
      according to a score by Kwasny revealed 6.2 points in group A and 2.2 points in
      group B (P < 0.0001; F = 46.9). The results of these two comparable groups
      suggest that conservative treatment of humeral shaft fractures is superior
      regarding mobility of the shoulder and elbow, strength, the incidence of
      neurological complications, pain, subjective rating and cosmesis. There were no
      differences on roentgenograms between the two groups (P = 0.48).

PMID- 9518205
TI  - [The prospects for Kirschner-wire osteosynthesis in the dorsally unstable distal
      radius fracture (Colles' type)].
AB  - The following experimental study was conducted to develop biocompatible methods
      of osteosynthesis in fractures of the distal radius and to evaluate their
      stability. A model of dorsal wedge osteotomy in the distal radial metaphysis was
      used to develop the surgical technique and to test the stability of the
      alternative methods of osteosynthesis. The concept for this model was based on
      commercially available materials which were either biodegradable or
      osteoconductive. Four different forms of biocompatible osteosynthesis were
      compared to combined Kirschner wire osteosynthesis (KWO), our preferred method of
      treatment of unstable Colles fracture. Biocompatible osteosynthesis was achieved
      with an invasivity and stability comparable to that of KWO. In conclusion,
      injection osteosynthesis exceeded the other biocompatible methods of
      osteosynthesis in all respects. Regarding the recent developments in injectable
      materials for osteosynthesis it offers the best perspective for clinical
      application.

PMID- 9518206
TI  - [Ligamentization as an explanation for the stability of periosteal flap repair in
      the replacement of the fibular ligament system].
AB  - The gold standard in the operative treatment of chronic insufficiency of the
      lateral ligaments of the ankle joint is replacement with a tendon (tenodesis).
      The disadvantage of this method is limitation of movement. The results of the
      replacement of ligaments with a periosteal flap are similar to the results after
      tenodesis, but the rate of complications is significant lower. We investigated
      the histological changes in periosteal flaps in patients. We saw an alignment of
      the collagenous fibers in the periosteal flap 8-12 weeks after the operation. The
      results are statistically significant. The conclusion is that the periosteal flap
      in the replacement of ligaments changes into a ligament-like structure.

PMID- 9518207
TI  - [3-dimensional sonography in the diagnosis of meniscal lesions. An experimental
      and clinical study].
AB  - There is no consensus regarding the clinical significance of conventional two
      dimensional ultrasound in the diagnosis of meniscal tears of the knee. Three
      dimensional ultrasound spatially reconstructs a transparent image of subsequent
      ultrasound scans. In an experimental study of 96 menisci, radial and oblique
      tears were detected more often by three-dimensional ultrasound. In a clinical
      study of 60 menisci the two- and three-dimensional ultrasound reached a
      sensitivity of 92% and 100%, a specificity of 83% and 88%, a positive predictive
      value of 58% and 67%, and a negative predictive value of 98% and 100%,
      respectively. Altogether, there was no statistically significant difference
      between both methods. The high negative predictive value, however, shows that the
      three-dimensional ultrasound may be a clinically relevant examination for special
      questions in the diagnostics of meniscal tears.

PMID- 9518209
TI  - [Infection prophylaxis in complex limb trauma through immediate definitive
      reconstruction via a free tissue transfer].
AB  - The concept of emergency free tissue transfer for severe extremity injuries
      represents a cutting-edge technology. We discuss our very positive results with
      this technique. The conceptual reasons for these favorable results, compared with
      conventional approaches, are also discussed. An initial, radical debridement is
      the most important part of the operation. This is then followed by
      osteosynthesis. The correct type of free tissue transfer is chosen according to
      the requirements of the soft tissue defect. Qualitatively better results with
      earlier definitive rehabilitation were achieved with free tissue transfer
      performed during the acute stage of limb wound treatment. The follow-up period
      ranged from 3 months to 8 years. We experienced neither flap loss, osteomyelitis,
      nor severe wound infection. Using the modern concept of emergency free tissue
      transfer, we reduced the rate of flap loss and associated morbidity while
      achieving a functionally improved reconstruction.

PMID- 9518208
TI  - [The determinants of the quality of life after a type-III open tibial fracture.
      The results of a multicenter study].
AB  - This study investigated to what extent quality of life four years or more after
      the fracture is determined by initial staging (Gustilo subclassification, time
      from injury to arrival at hospital), by the therapeutic course (length of
      hospital stay, number of operations), by complications (amputation, infection)
      and by demographic factors (gender, age). A total of 197 patients after type III
      open tibial shaft fractures (type IIIA 70, type IIIB 85, type IIIC 42) from nine
      centers volunteered to participate in this study. During patients' follow-up
      appointments (mean duration of follow-up 50 months), therapeutic course, pre
      surgical staging and demographic data were recorded by the surgeon. Patients were
      asked to rate quality of life on the Nottingham Health Profile and on a visual
      analogue scale. Multiple regression analysis (stepwise) identified two predictors
      for reducing overall quality of life (F-test: P = 0.007): number of operations
      (adjusted beta: -0.21) and age (adjusted beta: -0.17). Other factors showed no
      significant relationship with overall quality of life or with subscales of the
      Nottingham Health Profile. These findings indicate a dilemma between two
      therapeutic goals: good functional outcome, which often requires repeated
      operations, and quality of life, which suffers under prolonged surgical
      treatment.

PMID- 9518210
TI  - [The distally pedicled suralis flap for the defect coverage of posttraumatic and
      chronic soft-tissue lesions in the "critical" lower leg].
AB  - Vascular diseases and/or sequelae of various systemic diseases are frequently
      associated with therapy-resistant soft tissue lesions in the lower extremity.
      Neurovascular pedicled island flaps without the need for the sacrifice of major
      vessels offer the possibility to save the lower limb from amputation. The long
      pedicle allows for a wide, tension-free arc of rotation. Major studies of
      clinical applications at the critical lower extremity have not been reported yet.
      14 patients with chronic ulcerations in problematic areas (e.g. ankle, tibia)
      underwent definitive reconstruction using this flap. Complications were mostly
      observed at the donor site. In one patient major amputation was necessary due to
      the development of sepsis. In all other cases adequate coverage and limb salvage
      was achieved. Excellent padding, variable size and the modest nature of the flap
      enlarges the variety of plastic-reconstructive procedures in the lower extremity.

PMID- 9518211
TI  - [The osteosynthesis implant and early postoperative infection: healing with or
      without removal of the material?].
AB  - This prospective study served as a quality control of a revision concept for case
      of post-traumatic infection following open reduction and internal fixation in
      fracture treatment. It is based on clinical and microbiological criteria and has
      two aims: (1) eradication of the infection and avoidance of development of
      chronic osteitis; (2) maintenance of internal fixation, if possible. Thirty-four
      patients were recruited in this study. Surgical revisions were performed
      according to a consistent concept (debridement, irrigation, local chemotherapy,
      drainage) in defined time intervals (2 days). The operation site had to be
      bacteriologically clean after four revisions. Otherwise, the implant had to be
      removed. Both aims were reached in 11 cases: management of infection with
      maintenance of internal fixation. In 23 cases the implant material had to be
      removed. Nevertheless the infection was eliminated in all these patients without
      exception. The following risk factors for mandatory implant removal were
      evaluated: diabetes, arteriosclerosis, alcoholism, nicotine. This revision
      concept helps in the management of acute postoperative osteitis following ORIF in
      fracture treatment and in avoiding the development of chronic osteitis.

PMID- 9518213
TI  - [Scaphocapitate dislocation-fracture of the wrist joint in the setting of
      multiple injury].
AB  - Scaphocapitate fracture syndrome (SCFS) as part of perilunar distortion injuries
      (PL, PLF) in the human wrist is still remarkably rare. The diagnosis is
      determined by careful physical and radiological examinations, including
      conventional radiographs. Computed tomography can be helpful in detecting such
      lesions. In our opinion, the high risk of post-traumatic arthrosis because of
      carpal instability in a osteoligamental injury requires operative reconstruction
      in nearly all cases. We report the possibility of operative treatment in a case
      of scaphocapitate fracture syndrome (Fenton) by implantation of 2-mm mini-bone
      screws, while the use of K-wires or Herbert bone screws has been described in
      former articles.

PMID- 9518212
TI  - [The value of leukocyte scintigraphy in suspected implant infection in patients
      with chronic polyarthritis].
AB  - When infection of implants is suspected, optimal management requires accurate
      confirmation or exclusion of infection. However, in spite of demonstrative
      clinical signs cultures of smears or chemical parameters of inflammation
      frequently are ambiguous. Scintigraphy with indium-labeled white blood cells
      (WBC) has been reported to be sensitive and specific in the diagnosis of low
      grade sepsis of the musculoskeletal system. Twenty-eight patients with possible
      infection were prospectively studied. Infection was suspected in 19 cases with
      total hip joint prosthesis, 14 cases with knee joint prosthesis and 1 case with
      shoulder joint prosthesis. All of them underwent scanning with indium-111-labeled
      WBC and subsequently underwent surgery. At surgery infections were determined by
      means of culture or histologic results. When correlated with culture and
      histologic results sensitivity of 111-indium-WBC imaging was 89% with a
      specificity of 67% and a predictive accuracy of 77%. In patients with rheumatoid
      arthritis, however, predictive accuracy of 111-indium-labeled WBC imaging was
      higher than with standard diagnostic methods. The difference was statistically
      significant (P < 0.05, chi(2)-test). In the patients examined as a whole,
      predictive accuracy of 111-indium-labeled WBC imaging does not differ from that
      of standard diagnostic methods. That is why expensive and time-consuming 111
      indium-WBC imaging is not justified generally in diagnosis of infection of
      implants. 111-Indium-WBC imaging is well suited to supplement standard diagnostic
      methods in patients with rheumatoid arthritis.

PMID- 9518214
TI  - [Tendovaginitis stenosans of the thumb in small children (pollex flexus
      congenitus). The authors' results and review of the literature].
AB  - Our personal treatment concept for trigger thumb in children is presented. The
      guiding symptoms are fixed flexion deformity, (painful) restriction of motion
      (with a click phenomenon) or persistent extension deformity. Although it is a
      simple pathology, careful diagnosis is mandatory to rule out other reasons with
      the same symptoms as trigger thumb, as some of these will lead to severe
      aesthetic and functional impairment. In 26 patients with persistent symptoms, the
      A1 ring ligament of the thumb was cut. Free active and passive joint motion was
      comparable to the opposite side in 92.7% of patients. In 2 cases a secondary
      operation was necessary because of incomplete A1 ring ligament release. If it is
      diagnosed and operated on early with a careful operative technique, nowadays no
      aesthetic or functional impairment should occur in children because of trigger
      thumb.

PMID- 9518216
TI  - [The short bowel syndrome].

PMID- 9518215
TI  - [A comparison of a fluoroscopy-free mechanical targeting system and a free-hand
      technic for the placement of distal interlocking screws of tibial nails].
AB  - Recently, radiation-independent aiming devices for the tibia which compensate for
      insertion-related implant deformation have been developed, but the benefits of
      such systems have not been determined. This study prospectively evaluated the
      duration of the nailing procedure, the length of radiation time, and the accuracy
      of interlocking screw placement with a radiation-independent distal aiming system
      and the free-hand technique. In an oblique cadaveric tibial fracture, a surgeon
      inexperienced with either technique performed a statically locked intramedullary
      nailing. For the aiming system and free-hand technique respectively, the total
      operation time was 25.4 +/- 11.3 vs 30.9 +/- 14.3 min (P = 0.029), the distal
      locking time was 16.7 +/- 8.6 vs 21.9 +/- 10.5 min (P = 0.004), the total
      fluoroscopy time was 9 +/- 5 vs 93 +/- 34 s (P < 0.0001), the distal locking
      fluoroscopy time was 0 versus 88 +/- 33 s (P < 0.0001), and the screw destruction
      was -0.7 +/- 5.2 vs 26.8 +/- 31.6 microns (P = 0.001). The failure rate was 1.6%
      (1 of 60 screws) in both groups. These results suggest that aiming devices can
      eliminate the need for radiation during distal interlocking screw placement.

PMID- 9518217
TI  - [Ambulatory laparoscopic cholecystectomy].

PMID- 9518218
TI  - [The diagnosis and therapy of ligament injuries of the foot].

PMID- 9518219
TI  - Imaging of the pituitary in children with growth disorders.
AB  - Magnetic resonance imaging reveals the anatomy of the pituitary and hypothalamus
      with unique detail. The clinical and biochemical investigation of short stature
      in childhood may be difficult and complex; magnetic resonance imaging of the
      pituitary is a non-invasive technique which can help to clarify the diagnosis of
      growth hormone insufficiency and to determine its cause. Most cases of growth
      hormone insufficiency have previously been considered to be idiopathic; in about
      60% of these children, magnetic resonance imaging shows a characteristic
      structural abnormality which has been termed pituitary stalk interruption
      syndrome. The most important role of magnetic resonance imaging is in the
      diagnosis of destructive lesions of the hypothalamic-pituitary axis which may
      initially present with growth failure.

PMID- 9518220
TI  - Advances in paediatric CNS ultrasound.
AB  - Advanced paediatric ultrasound of the central nervous system (CNS) requires 7 MHz
      sector and linear transducers, equipment which is highly sensitive to flow
      velocity (Power Doppler) and additional transcranial axial, coronal and sagittal
      imaging. New diagnostic possibilities include recognition of subarachnoid
      hemorrhage (imaging of cisterns and/or CSF-flow); differentiation between
      subarachnoid and subdural fluid collections (colour flow imaging of traversing
      veins); additional criteria suggestive of spinal cord tethering (spinal cord
      pulsations); and grey-white matter differentiation in newborn infants. A
      meticulous examination technique is mandatory when investigating suspected brain
      death, sinus venous thrombosis, diffuse early ischemia or viral (herpes)
      encephalitis. Anatomical areas such as the cerebral aqueduct, tentorium, Foramina
      of Luschka or circle of Willis which are not usually regarded as accessible to
      cerebral echography can be visualized by advanced transcranial imaging technique.
      Indications for transcranial scanning; shortcomings of cerebral ultrasound;
      measures to overcome limitations; and requirements for present and future
      ultrasound equipment are given and discussed in tables.

PMID- 9518221
TI  - Neurofibromatosis type 1 in children: MR imaging and follow-up studies of central
      nervous system findings.
AB  - PURPOSE: To determine the frequency, evolution and diagnostic impact of
      characteristic central nervous system MR imaging lesions in children with
      neurofibromatosis type 1 (NF1). SUBJECTS: We reviewed 89 children with
      established or clinically suspected disease. A final diagnosis of NF1 was made in
      72 (age range, 10 months to 14 years). RESULTS: Hyperintense lesions on long TR
      images were detected in 78% of patients, principally involving the basal ganglia,
      cerebellum and brain stem. In 30% of the globus pallidus lesions, hyperintensity
      was seen on short TR images, being usually isointense on IR T1 weighted images.
      Globus pallidus lesions did not enhance. Eight patients presented atypical
      unenhanced lesions showing either edema, mass effect or hypointensity on short TR
      images; 2 of them were considered symptomatic brain stem gliomas. Six other
      children showed one or more growing enhanced cerebral lesions classified as
      tumors. Other child developed a growing enhanced lesion that markedly decreased
      in the follow-up studies. Twenty patients (28%) had optic gliomas. In two
      children, under 6 years old, this tumor appeared de novo. Forty-five children had
      several follow-up MR imaging studies (mean interval, 3 years). Regression of the
      basal ganglia lesions, both in size and/or intensity was noticed in 42% of cases,
      enlargement or new appearance of lesions in 24.5%, mixed increased/decreased in
      7%, and stability in 26.5%. White matter lesions of the cerebellum and brain stem
      decreased in size in 40%, grew in 15.5%, showed a mixed increased/decreased
      pattern in 11%, and remained unchanged in 33.5% of cases. An involutional
      tendency of these lesions occurred in children older than 10 years, while
      progression was more frequent in younger children (P<0.05). CONCLUSIONS:
      Hyperintense lesions are highly prevalent and characteristic in patients with
      NF1. MR imaging contributed to a definitive diagnosis of NF1 in 53% of suspected
      cases. Follow-up studies are necessary in the evaluation of suspected NF1, even
      if the first examination is negative.

PMID- 9518222
TI  - B mode ultrasonography--spectrum of paediatric ocular disease.
AB  - BACKGROUND: Despite having appropriate sonographic equipment available many
      radiologists remain unfamiliar with B mode sonography of the eye. OBJECTIVE: This
      article reviews the advantages and disadvantages of B mode sonography of the
      paediatric eye. We illustrate the spectrum of eye abnormalities occurring in
      paediatric practice and the sonographic appearance of clinical entities for which
      sonography is appropriate. MATERIALS AND METHOD: We reviewed our experience of
      eye sonography within a paediatric radiology department over 8 years. A total of
      212 sonographic examinations were performed on 206 eyes in 103 children, aged
      from 3 days to 16 years (mean 4.6 years). RESULTS: Sonography was well tolerated
      by the children, was a very useful imaging modality and was the only diagnostic
      imaging modality required in 94%. Supplementary computed tomography (CT) was
      performed in ten of 206 eyes (5%) and magnetic resonance imaging (MR) was
      performed in two of 206 eyes (1%). CONCLUSIONS: B mode sonography is a very
      useful imaging modality for suspected ocular or orbital pathology in children and
      is often the appropriate first line investigation following clinical evaluation.
      Radiologists familiar with sonography of the eye can provide valuable support to
      their ophthalmology colleagues.

PMID- 9518223
TI  - Birth asphyxia.
AB  - The term Birth asphyxia covers a number of clinical and physiological
      definitions. Birth asphyxia is a relatively common clinical event. In the
      majority of cases the outcome in terms of brain damage and future development of
      the child is excellent. However, a small number of children go on to develop
      patterns of brain damage which are then associated with disability. The article
      seeks to provide a basic understanding of the various mechanisms involved in
      producing injury.

PMID- 9518224
TI  - Magnetic resonance--its current and future role in paediatric cardiac radiology.
AB  - Cardiac magnetic resonance (MR) has developed rapidly providing a method of both
      imaging congenital heart disease and assessing function using a variety of
      techniques. The aim of this review is to identify indications for MR and its
      relative strengths and weaknesses in comparison to other methods of cardiac
      imaging. A potential future role for MR is also discussed.

PMID- 9518225
TI  - Children's sports injuries.
AB  - Sports injuries in children are common. They range from very serious and even,
      occasionally, fatal accidents, to trivial sprains and bruises. Sports medicine is
      a burgeoning field. Parallel with this there has been an increased understanding
      of the radiology of these lesions. Lesions in the immature skeleton differ
      greatly to those in the mature skeleton. This review describes the most frequent
      sports injuries in children.

PMID- 9518226
TI  - Bone density in children: a review of the available techniques and indications.
AB  - The recent development of methods for measuring bone mineral content in children
      has markedly improved our ability to determine changes in bone mass during
      growth. Currently, the three most generally accepted techniques for measuring the
      bones of children are dual-energy X-ray absorbtiometry (DXA), quantitative
      computed tomography (QCT) and quantitative ultrasound (QUS). These techniques
      vary considerably in their acquisition of data and comparisons between them are
      difficult and, more often than not, judgment regarding their value has been, at
      least partially, subjective. DXA is, by far, the most widely used technique for
      bone measurements. It is low in cost, accessible, easy to use, and provides an
      accurate and precise quantitation of bone mass in adults. Unfortunately, DXA is
      unable to account for the large changes in body and skeletal size that occur
      during growth, limiting its use in longitudinal studies in children. QCT can
      asses both the volume and the density of bone in the axial and appendicular
      skeletons, without influence from body or skeletal size, giving it a major
      advantage over other modalities for bone measurements in children. The cost and
      inaccessibility of CT scanners, however, has significantly limited its use for
      bone measurements. Measuring the bones of children by QUS is appealing because
      ultrasound is low in cost, portable, easy to use and does not emit radiation. In
      adults, this technique is able to predict fracture risk independent of bone mass
      determinations in patients with osteoporosis and, therefore, its measurements
      must be related to certain aspects of bone strength. However, ultrasound values
      are dependent on so many structural properties not yet fully understood, that it
      is difficult to use the information meaningfully in children.

PMID- 9518227
TI  - The acute paediatric scrotum: the role of colour doppler ultrasound.
AB  - Combined grey scale ultrasound and colour Doppler imaging of the acute paediatric
      scrotum provides a non-invasive means of assessing the structure and perfusion of
      the testis. Colour flow ultrasound is a sensitive and specific diagnostic tool
      for differentiating ischaemic pathology (in which blood flow rate is reduced)
      from inflammatory disease in which it is commonly increased. Using this technique
      the number of unnecessary surgical explorations of the scrotum can be reduced.
      The differential diagnosis of acute testicular pathology and the imaging
      characteristics of each disorder are described. Close collaboration between
      paediatric surgeons and radiologists is required to determine the optimal
      clinical and investigational strategy for each child.

PMID- 9518228
TI  - The role of radiology in children with anorectal anomalies; with particular
      emphasis on MRI.
AB  - Anorectal anomalies have a reported incidence of between 1 per 1000 and 1 per
      9630 live births. The international classification subdivides anorectal
      malformations into high, intermediate, low and miscellaneous deformities with
      emphasis on the sex of the child. The classification is based on where the rectum
      terminates in relation to the levator ani muscles above the levator is termed a
      high (supralevator) lesion, at the level of the levator intermediate, and below
      is a low or translevator anomaly. A modified classification has recently been
      proposed by Pena based on his anatomic observations during posterior sagittal
      anorectoplasty-the terms high, intermediate and low lesions continue to be used
      but with slightly different connotations. Approximately 50% of all patients with
      anorectal anomalies have associated other congenital lesions. These lesions
      necessitate a variety of radiological investigations which will be outlined
      briefly. The pertinent muscular anatomy of the pelvic floor and recent advances
      in surgical techniques will be discussed. The particular role of MRI in the
      evaluation of the pre-operative newborn or infant prior to definitive pull
      through repair surgery and the post-operative, older, paediatric patient with
      continuing problems will be reviewed. Reference to the other radiological
      options, and their usefulness, in the evaluation of anorectal malformations will
      be made throughout the text.

PMID- 9518229
TI  - Bilateral adrenal ganglioneuroblastomas in a teenage boy.

PMID- 9518230
TI  - Acute torsion of a wandering spleen in a child: preoperative diagnosis by
      ultrasonography and computed tomography.

PMID- 9518231
TI  - Aneurysms of the portal venous system: ultrasonography and CT findings.
AB  - OBJECTIVE: The retrospective study of aneurysms of the portal venous system and
      their possible aetiology, using different imaging methods. MATERIAL AND METHODS:
      Between 1992 and 1995 we collected 13 cases of portal vein aneurysm from 11
      patients, eight of whom suffered portal hypertension (PH) secondary to hepatic
      cirrhosis. All were diagnosed by means of ultrasonography (155) and/or computed
      tomography (CT). The aneurysms were defined as fusiform expansions when in the
      main portal vein and its branches or as cystic lesions with internal flow when in
      the intrahepatic branches. RESULTS: Ten of the aneurysms (76.9%) were in the
      extrahepatic portal venous system and three (23.1%) in intrahepatic branches. Of
      the extrahepatic aneurysms, the two most common locations were the main portal
      vein and the confluence of superior mesenteric and splenic veins (30.7% each
      site). The largest were generally those at the confluence (37.6+/-9.7 mm maximum
      diameter). CONCLUSION: Aneurysms in the portal system can be congenital or
      acquired. Although their aetiology is uncertain, we found a clear relation to PH
      syndrome; of 13 aneurysms in the study, eight were related to this disease. PH
      should be suspected in the evaluation of portal aneurysms.

PMID- 9518232
TI  - The association between primary biliary cirrhosis and coeliac disease: a study of
      relative prevalences.
AB  - BACKGROUND: Coexistent primary biliary cirrhosis (PBC) and coeliac disease has
      been recorded but the association has not been systematically studied. AIMS: To
      determine relative prevalences of PBC and coeliac disease in a defined population
      over a 12 year period. PATIENTS AND METHODS: All patients with PBC or coeliac
      disease in a stable population of 250,000 in South Wales were identified from a
      clinical register and laboratory records. RESULTS: Sixty seven patients with PBC
      and 143 patients with coeliac disease have been diagnosed and followed over a
      median of 86 (4-135) months; point prevalences in 1996 were 20 per 100,000 for
      PBC and 54 per 100,000 for coeliac disease. PBC in patients with coeliac disease
      was sought by investigating abnormal liver function tests. Ten (7%) had
      persistent abnormalities and three had PBC. Coeliac disease in patients with PBC
      was sought by investigating malabsorption, haematinic deficiency, positive
      antigliadin antibody, or coeliac disease family history. Eleven patients
      underwent duodenal biopsy revealing one further coeliac disease case. Four
      patients (three women have both conditions giving a point prevalence for patients
      with both conditions of 1.6 per 100,000 (95% confidence limits 0.44 to 4.1 per
      100,000). Prevalence of PBC in patients with coeliac disease was 3% and of
      coeliac disease in patients with PBC was 6%. CONCLUSION: A 12 year study of a
      stable 250,000 population revealed a relative prevalence of PBC in 3% of 143
      patients with coeliac disease and of coeliac disease in 6% of 67 patients with
      PBC. PBC and coeliac disease are therefore associated. Screening for PBC in
      patients with coeliac disease using antimitochondrial antibody testing and
      screening for coeliac disease in patients with PBC with antigliadin antibody
      testing or duodenal biopsy are recommended.

PMID- 9518233
TI  - Abnormal mucus in cap polyposis.
AB  - BACKGROUND: Cap polyposis is a rare disease characterised by mucoid and bloody
      diarrhoea, with polyps covered by a cap of mucoid and fibrinopurulent exudate.
      The pathogenesis is not known. AIMS: To pour some light on cap polyposis
      pathogenesis, by examining the mucus of patients and analysing the expression of
      five mucin genes, MUC2, MUC3, MUC4, MUC5AC, and MUC5B. PATIENT AND METHODS: The
      study was performed on biopsy specimens taken from a patient with recurrent cap
      polyposis. Histochemical examination, electron microscopy, and mRNA in situ
      hybridisation were used. RESULTS: The mucus of cap polyposis differed in three
      respects from that of normal adult colon: abnormal ultrastructure of the mucus in
      the goblet cells, predominance of non-sulphated mucins, abnormal expression of
      the MUC4, MUC3, and MUC5AC genes. CONCLUSIONS: Most of these abnormalities have
      been reported for other pathological situations, suggesting that the
      abnormalities observed in the mucus of this patient with cap polyposis are
      probably secondary phenomena rather than primary. However, the mucin
      abnormalities detected, which reflect deregulation of the expression of three
      apomucin genes, abnormal glycosylation, and abnormalities of the secretion
      process, are also probably involved in the clinical manifestations of cap
      polyposis.

PMID- 9518234
TI  - Reducing risks in gastroenterological practice.
AB  - Eighty five malpractice claims against gastroenterologists have been analysed.
      Thirty seven (44%) arose from adverse events as a result of endoscopy and 48
      (56%) from clinical practice. In 31 (84%) of the endoscopy cases (including all
      13 endoscopic retrograde cholangiopancreatographies) there seemed to be
      significant fault. In nine cases the procedure was not clearly indicated and in
      10 recognition and treatment of the adverse event was delayed. In no case had the
      patient given adequate informed consent. Diagnostic error was responsible for
      most of the claims related to clinical practice (31 of 48) of which 13 were
      indefensible. Failure to obtain an adequate history (17 cases) and insufficient
      awareness of disorders of the small intense (12 cases) were major factors. In 26
      cases a key investigation was not performed. Seventeen claims were related to
      management or treatment but only one of these cases was difficult to defend.
      Overall, there was evidence of serious fault in 50% of claims. Greater care in
      selecting patients for endoscopic procedures and in providing postprocedural care
      would have eliminated the basis of more than half the claims arising from
      endoscopy. There would have been few claims if properly informed consent had been
      obtained. Over-ready acceptance of the diagnosis of a functional disorder (for
      example, irritable bowel, dyspepsia) was the usual cause of delays in diagnosis.

PMID- 9518235
TI  - Transcription Factors in Immunology. Proceedings of a conference. Muenchen,
      Germany, November 20-23, 1996.

PMID- 9518236
TI  - Advances in Andrology. Proceedings of a meeting. Freiburg, Germany, 20-22 March
      1997.

PMID- 9518237
TI  - Neoral in Psoriasis. Proceedings from a roundtable meeting. Phoenix, Arizona,
      USA. January 21-22, 1997.

PMID- 9518238
TI  - [Epidural lipomatosis as a complication of glucocorticoid treatment].
AB  - Epidural lipomatosis can be induced by systemic glucocorticoid treatment and may
      cause severe neurologic deficits. So far, 41 patients have been reported in the
      literature. Early recognition of this rare, relatively unknown, but extremely
      important side effect of exogenously administered glucocorticoids can help avoid
      persistent neurological sequelae.

PMID- 9518239
TI  - [Allergies and pseudoallergic reactions to anesthetics. The clinical symptoms,
      risk factors and the diagnostic possibilities].
AB  - Nearly all drugs currently used during the course of general anaesthesia may lead
      to hypersensitivity reactions of various types. There may be an acute type I
      allergic reactions or to a more or less severe pseudo-allergic reactions, in rare
      cases with lethal outcome. Routine preoperative testing appears of little
      predictive value, in spite of the high frequency of so-called risk factors
      (atopy, other kind of allergy) among the evaluated group of patients. Careful
      allergological testing should be performed 4 to 6 weeks after any incidents of
      suspected drug intolerance, in order to discover the underlying causative agent.
      Skin testing is of diagnostic value for neuromuscular blockers and intravenous
      narcotics. RAST- and RIA-tests and/or mediator releasing tests may also used
      additionally. Together with all other administered drugs, all the routinely used
      neuromuscular blockers (suxamethonium, vecuronium, pancuronium, alcuronium,
      atracurium, mivacurium) should be tested, since they often represent the cause
      for such reactions. For other classes of drugs (for example, volatile anesthetics
      and opioids) the clinical relevance of skin testing still remains uncertain. For
      less severe incidents seen during general anaesthesia such as pruritus, or
      exanthema, skin testing seems to be less relevant.

PMID- 9518240
TI  - [The Clark-Howel-Evans-McConnell syndrome. Observations in one family over 5
      generations].
AB  - The Clarke-Howel-Evans-McConnell syndrome is a rare hereditary disease
      characterized by palmoplantar keratoses, squamous cell carcinoma of the esophagus
      and oral leukoplakia. According to a new classification recently proposed by
      Stevens and colleagues, the syndrome can also be classified as palmoplantar
      ectodermal dysplasia type III. We report a family from the Black Forest region of
      Germany afflicted with the syndrome. The family was traced through five
      generation. 27 of 46 family members showed tylotic skin changes. In addition, 8
      patients showed oral leukoplakia and 5 died from squamous cell carcinoma of the
      esophagus. Using screening examinations, early changes of the esophageal mucosa
      could be detected. The responsible gene has been mapped in the family. It is
      located at 17q23-qter, telomeric to the keratin II gene cluster. Therefore a
      defect in one of the well known keratin genes can be excluded as a cause of the
      syndrome.

PMID- 9518241
TI  - [The effect of compression therapy on the microcirculation of the skin in
      patients with chronic venous insufficiency (CVI)].
AB  - Compression therapy was employed for 4 weeks 20 patients with chronic venous
      insufficiency stage CVI I and CVI II according to Widmer's classification.
      Compression bandaging for 2 weeks was followed by compression stockings for 2
      more weeks. The cutaneous microcirculation was evaluated before therapy, after 2
      weeks and after finishing compression therapy after 4 weeks. Marked improvement
      in symptoms such as pain and itching was observed after 4 weeks, along with a
      significant reduction in lower limb volume. Video capillary microscopy revealed
      an increase in capillary density associated with a decrease in capillary diameter
      and pericapillary halo diameter. Compression treatment achieves at least part of
      its effect by improving the function of the skin microcirculation. The efficacy
      of bandaging and stockings was similar.

PMID- 9518242
TI  - [Epicutaneous testing with gold salts. 2 multicenter studies of the German
      Contact Allergy Group].
AB  - Between 1992 and 1994 two multicentre studies were performed in order to
      determine the frequency of sensitization to gold salts. In the first study (1992
      1993), 872 patients were tested with gold sodium thiosulfate (NTS) 0.25% in
      Vaseline (V), 0.5% V. and with potassium dicyanoaurate (KDC) 0.002% aqueous
      solution. 44 patients (5.1%) had a positive patch test reaction to gold salts: 40
      (4.6%) to NTS 0.5% V., 20 (2.3%) to NTS 0.25% V. and 5 (0.6%) to KDC. A higher
      number of positive patch tests to gold salts was noted in patients also
      sensitized to another metal salt (8.5%) as compared to those who showed no other
      sensitivities (3.6%). In a second multicentre study (1993-1994), 135 patients
      with associated sensitization to metal salts or intolerance to costume
      [correction of custom] jewelry were tested with the same test series as in the
      first study and with gold sodium thiomalate (ATM) 0.25% V.17 patients (12.6%) had
      a positive patch test reaction to gold salts: 16 (11.8%) to NTS 0.5% V., 10
      (7.4%) to NTS 0.25% V. and 5 (3.7%) to ATM. The clinical relevance of the patch
      test reactions was considered as being "probable" in 5 cases; 1 in the first and
      4 in the second study. Considering these results, NTS 0.5% V. seems to be the
      most reliable allergen for detecting gold allergy. However, a high proportion of
      probably false-positive reactions may occur. Further studies are therefore needed
      to analyze if the high frequency of positive patch tests to NTS 0.5% V. are due
      to irritant reactions or to a weak sensitization to gold without clinical
      symptoms.

PMID- 9518243
TI  - [Subcutaneous sweat gland suction curettage in tumescent local anesthesia in
      hyperhidrosis axillaris].
AB  - We surgically treated twenty patients with axillary hyperhidrosis by liposuction
      using tumescent regional anesthesia. After a description of the surgical
      technique results are presented. Except for trivial hematomas, no complications
      were seen. Every patient noted a significant reduction of sweat gland activity in
      the follow up period. Long-term results remain to be seen.

PMID- 9518244
TI  - [The successful monotherapy of hypereosinophilic dermatitis with PUVA-bath
      photochemotherapy].
AB  - A 70-year-old woman with long-standing hypereosinophilic dermatitis improved
      strikingly with PUVA-bath photochemotherapy. The single UVA doses ranged from 0.3
      to 3.3 J/cm2. After 19 treatment sessions pruritus disappeared, and after 32
      treatments the erythematous maculae completely cleared. Under continuous
      treatment three times a week, no relapse has occurred to date. PUVA-bath
      photochemotherapy seems to be a promising new treatment modality without systemic
      side effects for patients with hypereosinophilic dermatitis.

PMID- 9518246
TI  - [Persistent facial swelling of unclear etiology. The differential diagnostic
      considerations].
AB  - A 54-year-old, obese woman suffered from massive symmetrical swelling of the
      face, especially of the upper and lower eyelids. Initially the swelling occurred
      intermittently, but after 2 years it was permanent and progressive markedly
      limiting her visual fields. Neither laboratory findings nor imaging procedures
      provided any firm evidence of an underlying cardiac, renal or endocrinological
      disease. There was no suggestion of a storage disease. Skin biopsy showed foam
      cells and granulomatous inflammation, so the patient was tentatively diagnosed as
      having a monosymptomatic Melkersson-Rosenthal Syndrome. Eyelid surgery was
      performed to improve her visual fields. Treatment with clofazimine 100 mg daily
      was initiated. Regular follow-up visits over 7 months revealed no evidence of
      recurrence. The patient died a sudden cardiac death a few months later. The
      relatives refused an autopsy. The definite cause of her facial swelling remains
      unclear as we discuss the differential diagnostic possibilities.

PMID- 9518245
TI  - [PUVA-bath photochemotherapy in Hallopeau's acrodermatitis continua suppurativa].
AB  - A 73-year-old man presented with severe, relapsing acrodermatitis continua of
      Hallopeau, which had been resistant to prior local and systemic therapy for eight
      years. The patient was treated with selective hand PUVA-bath photochemotherapy.
      The cumulative dose of UVA used over 10 weeks of treatment was 54.6 J/cm2 on the
      palms and 26.8 J/cm2 on the dorsum of the hands. The single UVA doses ranged from
      0.5 to 2.5 J/cm2 on the palms and 0.2 to 1.4 J/cm2 on the dorsum of the hands.
      After 16 treatment sessions, the acrodermatitis continua started to improve, and
      after 24 treatments, had cleared completely. In the four months following the
      PUVA therapy, there was no relapse. PUVA-bath photochemotherapy is an efficient
      therapeutic alternative in the treatment of acrodermatitis continua due to its
      clinical effectiveness and lack of any systemic side effects. It also possesses
      the advantage of allowing selective photosensitization of certain areas of the
      skin such as the hands.

PMID- 9518247
TI  - [Bullous pemphigoid as a paraneoplastic syndrome. A case report in renal-cell
      carcinoma].
AB  - Paraneoplastic markers in tumor patients may occur at various stages of the
      disease. While some disorders almost invariably herald an underlying malignancy
      (obligative marker), most only occasionally do so (facultative marker). The
      association of bullous pemphigoid with malignancy is controversial. There are
      only a few reports of bullous pemphigoid associated with a renal cell carcinoma.
      We diagnosed a renal cell carcinoma in a 74 year old female patient, admitted to
      the hospital because of bullous pemphigoid. Multiple metastases were found in her
      lymph nodes, liver, lung and skeleton. The patient died eleven weeks after the
      first symptoms of bullous pemphigoid appeared.

PMID- 9518248
TI  - [The differential diagnosis of nevus/melanoma].

PMID- 9518249
TI  - [The Union of Southwest German Dermatologists--the light and shadow of a regional
      society].

PMID- 9518250
TI  - [PUVA-turban therapy].

PMID- 9518251
TI  - [The 1996 annual meeting of the German STD Society in Rostock-Warnemunde].

PMID- 9518252
TI  - [The 2nd Bad Homburg Expert Colloquium on malignant melanoma and other skin
      tumors].

PMID- 9518253
TI  - [Low-molecular-weight heparins. The prevention and therapy of thromboembolic
      diseases].

PMID- 9518254
TI  - ["Directed activities for securing our position"].

PMID- 9518255
TI  - [Clarification within the framework of medical activities].

PMID- 9518256
TI  - Inhibitors of in vitro mineralization from rabbit aorta and their role in
      biomineralization.
AB  - Mineralization of aorta is known to occur late in life and appears to be a
      pathological phenomenon. In vitro studies revealed that the matrix prepared from
      the thoracic aorta pieces after their extraction with 3% Na2HPO4 and 0.1 mM CaCl2
      were mineralized under physiological conditions of temperature, pH, and ionic
      strength of the media to form matrix-bound mineral phase resembling
      hydroxyapatite in nature. However, the matrix identically prepared from the
      unextracted rabbits aortae failed to mineralize under identical assay conditions.
      The addition of the aorta extract in the assay system inhibited the above
      mineralization process. Standard biochemical techniques, e.g., dialysis, ion
      exchange, and molecular sieve chromatography, sodium dodecyl sulfate
      polyacrylamide gel electrophoresis, and amino acid analysis by high-performance
      liquid chromatography were employed to isolate, purify, and characterize the
      potent inhibitory biomolecules from the aorta extract. The inhibitory activity of
      the aorta extract was found to be primarily due to the presence of three
      biomolecules having molecular weights of 66, 45, and 27-29 kDa. The above
      inhibitory biomolecules loosely associated with aorta may be involved in the
      control of calcification associated with arteriosclerosis.

PMID- 9518257
TI  - Glucocorticoids repress induction by thiazolidinediones, fibrates, and fatty
      acids of phosphoenolpyruvate carboxykinase gene expression in adipocytes.
AB  - Phosphoenolpyruvate carboxykinase (PEPCK) exerts a glyceroneogenic function in
      adipocytes in which transcription of its gene is increased by unsaturated fatty
      acids and fibrates. We used cultured rat adipose tissue fragments and 3T3-F442A
      adipocytes to show that the antidiabetic thiazolidinedione BRL 49653, a ligand
      and an activator of the gamma isoform of peroxisome proliferator activated
      receptors (PPARgamma), is a potent inducer of PEPCK mRNA. In 3T3-F442A
      adipocytes, the effect of BRL 49653 is rapid and concentration dependent, with a
      maximum reached at 1 microM and a half-maximum at 10-100 nM. PEPCK mRNA is
      similarly induced by the natural ligand of PPARgamma, the 15-deoxy-delta(12-14)
      prostaglandin J2. These observations strongly suggest that PPARgamma is a primary
      regulator of PEPCK gene expression in adipocytes. Dexamethasone at 10 nM repress
      induction of PEPCK mRNA by 1 microM BRL 49653, 0.32 mM oleate, or 1 mM
      clofibrate, in a cycloheximide-independent manner. The antiglucocorticoid RU
      38486 prevents dexamethasone action, demonstrating involvement of the
      glucocorticoid receptor. Stable transfectants of 3T3-F442A adipocytes bearing 
      2100 to +69 base pairs of the PEPCK gene promoter fused to the chloramphenicol
      acetyltransferase (CAT) gene respond to 1 microM BRL 49653 or 1 mM clofibrate by
      a large increase in CAT activity, which is prevented by the simultaneous addition
      of 10 nM dexamethasone. Hence, in adipocytes, glucocorticoids act directly
      through the 5'-flanking region of the PEPCK gene to repress, in a dominant
      fashion, the stimulation of PEPCK gene transcription by thiazolidinediones and
      fibrates.

PMID- 9518258
TI  - Oct-1 enhances the in vitro replication of a mammalian autonomously replicating
      DNA sequence.
AB  - A 186-base pair fragment of ors8, a mammalian autonomously replicating DNA
      sequence isolated by extrusion of nascent monkey DNA in early S phase, has
      previously been identified as the minimal sequence required for replication
      function in vitro and in vivo. This 186-base pair fragment contains, among other
      sequence characteristics, an imperfect consensus binding site for the ubiquitous
      transcription factor Oct-1. We have investigated the role of Oct-1 protein in the
      in vitro replication of this mammalian origin. Depletion of the endogenous Oct-1
      protein, by inclusion of an oligonucleotide comprising the Oct-1 binding
      site,inhibited the in vitro replication of p186 to approximately 15-20% of the
      control, whereas a mutated Oct-1 and a nonspecific oligonucleotide had no effect.
      Furthermore, immunodepletion of the Oct-1 protein from the HeLa cell extracts by
      addition of an anti-POU antibody to the in vitro replication reactioninhibited
      p186 replication to 25% of control levels. This inhibition of replication could
      be partially reversed to 50-65% of control levels, a two- to threefold increase,
      upon the addition of exogenous Oct-1 POU domain protein. Site-directed
      mutagenesis of the octamer binding site in p186 resulted in a mutant clone, p186
      MutOct, which abolished Oct-1 binding but was still able to replicate as
      efficiently as the wild-type p186. The results suggest that Oct-1 protein is an
      enhancing component in the in vitro replication of p186 but that its effect on
      replication is not caused through direct binding to the octamer motif.

PMID- 9518259
TI  - Heparin-binding EGF-like growth factor in the human prostate: synthesis
      predominantly by interstitial and vascular smooth muscle cells and action as a
      carcinoma cell mitogen.
AB  - Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is an
      activating ligand for the EGF receptor (HER1/ErbB1) and the high-affinity
      receptor for diphtheria toxin (DT) in its transmembrane form (proHB-EGF). HB-EGF
      was immunolocalized within human benign and malignant prostatic tissues, using
      monospecific antibodies directed against the mature protein and against the
      cytoplasmic domain of proHB-EGF. Prostate carcinoma cells, normal glandular
      epithelial cells, undifferentiated fibroblasts, and inflammatory cells were not
      decorated by the anti-HB-EGF antibodies; however, interstitial and vascular
      smooth muscle cells were highly reactive, indicating that the smooth muscle
      compartments are the major sites of synthesis and localization of HB-EGF within
      the prostate. In marked contrast to prostatic epithelium, proHB-EGF was
      immunolocalized to seminal vesicle epithelium, indicating differential regulation
      of HB-EGF synthesis within various epithelia of the reproductive tract. HB-EGF
      was not overexpressed in this series of cancer tissues, in comparison to the
      benign tissues. In experiments with LNCaP human prostate carcinoma cells, HB-EGF
      was similar in potency to epidermal growth factor (EGF) in stimulating cell
      growth. Exogenous HB-EGF and EGF each activated HER1 and HER3 receptor tyrosine
      kinases and induced tyrosine phosphorylation of cellular proteins to a similar
      extent. LNCaP cells expressed detectable but low levels of HB-EGF mRNA; however,
      proHB-EGF was detected at the cell surface indirectly by demonstration of
      specific sensitivity to DT. HB-EGF is the first HER1 ligand to be identified
      predominantly as a smooth muscle cell product in the human prostate. Further, the
      observation that HB-EGF is similar to EGF in mitogenic potency for human prostate
      carcinoma cells suggests that it may be one of the hypothesized stromal mediators
      of prostate cancer growth.

PMID- 9518260
TI  - Thiol redox modulation of tumor necrosis factor-alpha responsiveness in cultured
      AIDS-related Kaposi's sarcoma cells.
AB  - Both clinical and experimental evidence indicates that AIDS-related Kaposi's
      sarcoma (AIDS-KS) has a multifactorial pathogenesis with factors such as HIV
      viral load, latent virus induction, and opportunistic infections contributing to
      disease progression. However, a consistent feature that unites these apparently
      diverse putative etiologic agents is sustained serum elevations of pro
      inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha). While
      virtually every cell responds to TNF-alpha with gene activation, the extent of
      TNF-alpha-mediated cellular signaling is regulated by a delicate balance between
      signal activation and signal arresting events. Reactive oxygen intermediates
      (ROI), which are generated as a consequence of TNF-alpha membrane interaction,
      are part of this TNF-alpha-initiated cellular activation cascade. Previous
      studies in our laboratory have shown that AIDS-KS cells possess impaired oxygen
      intermediate scavenging capacities, thereby establishing conditions permissive
      for the intracellular retention of ROI. In this study, we used cellular capacity
      to upregulate the cytoprotective enzyme superoxide dismutase (SOD) to address the
      extent of cellular response to TNF-alpha. Concurrent with the SOD analyses,
      nucleotide profiles were obtained to assess cellular bioenergetic responses
      during TNF-alpha challenge. Proliferative growth levels of mitochondrial (Mn)SOD
      activities showed an activity spectrum ranging from lowest activity in AIDS-KS
      cells, to intermediate levels in matched, nonlesional cells from the AIDS-KS
      donors, to highest activities in HIV normal fibroblasts. In contrast, following
      TNF-alpha challenge, the AIDS-KS and KS donor nonlesional cells showed a 11.89-
      and 5.86-fold respective increase in MnSOD activity, while the normal fibroblasts
      demonstrated a 1.35-fold decrease. Subsequent thiol redox modulation studies
      showed that only the normal fibroblast cultures showed a potentiation of TNF
      alpha-mediated MnSOD upregulation following GSH depletion. In addition, provision
      of the GSH precursor, N-acetylcysteine during TNF-alpha challenge only diminished
      MnSOD activity and mitochondrial compartmentalization in the AIDS-KS cells, a
      finding that likely reflects the lower levels of reduced thiols in this cellular
      population. Our data, which show that a perturbation in their cellular thiol
      redox status accentuates AIDS-KS cellular responsiveness to TNF-alpha, suggest a
      biochemical rationale for the recognized TNF-alpha AIDS-KS clinical correlation.

PMID- 9518261
TI  - Analysis of differential gene expression in rat tibia after an osteogenic
      stimulus in vivo: mechanical loading regulates osteopontin and myeloperoxidase.
AB  - The skeleton has the ability to alter its mass, geometry, and strength in
      response to mechanical stress. In order to elucidate the molecular mechanisms
      underlying this phenomenon, differential display reverse transcriptase-polymerase
      chain reaction (DDRT-PCR) was used to analyze gene expression in endocortical
      bone of mature female rats. Female Sprague-Dawley rats, approximately 8 months
      old, received either a sham or bending load using a four-point loading apparatus
      on the right tibia. RNA was collected at 1 h and 24 h after load was applied,
      reverse-transcribed into cDNA, and used in DDRT-PCR. Parallel display of samples
      from sham and loaded bones on a sequencing gel showed several regulated bands.
      Further analysis of seven of these bands allowed us to isolate two genes that are
      regulated in response to a loading stimulus. Nucleotide analysis showed that one
      of the differentially expressed bands shares 99% sequence identity with rat
      osteopontin (OPN), a noncollagenous bone matrix protein. Northern blot analysis
      confirms that OPN mRNA expression is increased by nearly 4-fold, at 6 h and 24 h
      after loading. The second band shares 90% homology with mouse myeloperoxidase
      (MPO), a bactericidal enzyme found primarily in neutrophils and monocytes.
      Semiquantitative PCR confirms that MPO expression is decreased 4- to 10-fold, at
      1 h and 24 h after loading. Tissue distribution analysis confirmed MPO expression
      in bone but not in other tissues examined. In vitro analysis showed that MPO
      expression was not detectable in total RNA from UMR 106 osteoblastic cells or in
      confluent primary cultures of osteoblasts derived from either rat primary
      spongiosa or diaphyseal marrow. Database analysis suggests that MPO is expressed
      by osteocytes. These findings reinforce the association of OPN expression to bone
      turnover and describes for the first time, decreased expression of MPO during
      load-induced bone formation. These results suggest a role for both OPN and MPO
      expression in bone cell function.

PMID- 9518262
TI  - Overexpression of membrane glycoprotein PC-1 can influence insulin action at a
      post-receptor site.
AB  - An elevated content of membrane glycoprotein PC-1 has been observed in cells and
      tissues of insulin resistant patients. In addition, in vitro overexpression of PC
      1 in cultured cells induces insulin resistance associated with diminished insulin
      receptor tyrosine kinase activity. We now find that PC-1 overexpression also
      influences insulin receptor signaling at a step downstream of insulin receptor
      tyrosine kinase, independent of insulin receptor tyrosine kinase. In the present
      studies, we employed Chinese hamster ovary cells that overexpress the human
      insulin receptor (CHO IR cells; approximately 10(6) receptors per cell), and
      transfected them with human PC-1 c-DNA (CHO IR PC-1). In CHO IR PC-1 cells,
      insulin receptor tyrosine kinase activity was unchanged, following insulin
      treatment of cells. However, several biological effects of insulin, including
      glucose and amino acid uptake, were decreased. In CHO IR PC-1 cells, insulin
      stimulation of mitogen-activated protein (MAP) kinase activity was normal,
      suggesting that PC-1 overexpression did not affect insulin receptor activation of
      Ras, which is upstream of MAP kinase. Also, insulin-stimulated
      phosphatidylinositol (PI)-3-kinase activity was normal, suggesting that PC-1
      overexpression did not interfere with the activation of this enzyme by insulin
      receptor substrate-1. In these cells, however, insulin stimulation of p70
      ribosomal S6 kinase activity was diminished. These studies suggest, therefore,
      that, in addition to blocking insulin receptor tyrosine kinase activation, PC-1
      can also block insulin receptor signaling at a post-receptor site.

PMID- 9518263
TI  - Effects of conformationally restricted synthetic retinoids on ovarian tumor cell
      growth.
AB  - We have used conformationally restricted retinoids to investigate the role of
      individual RAR subtypes and RXR in mediating the growth response of ovarian tumor
      cells to retinoids. Our results show that treatment of all-trans-RA-sensitive
      CAOV-3 cells with retinoids that bind and activate a single RAR or RXR led to a
      partial inhibition of growth. Treatment of all-trans-RA- resistant SKOV-3 cells
      did not alter growth. Maximum inhibition of growth, comparable to that observed
      following treatment with natural retinoids such as all-trans-RA and 9-cis-RA, was
      obtained only following treatment with a combination of an RAR-selective compound
      and an RXR-selective one. These results suggest that activation of both RAR and
      RXR classes is required in order to obtain maximum inhibition of ovarian tumor
      cell growth by retinoids. In addition, one compound, AHPN, was found to inhibit
      both RA-sensitive CAOV-3 and RA-resistant SKOV-3 cells. Further study of the
      effects of this retinoid showed that AHPN acts through an apoptotic pathway.
      Taken together, our results suggest that retinoids may serve as effective anti
      proliferative agents in the treatment of ovarian cancer.

PMID- 9518265
TI  - JCU in the on-line era.

PMID- 9518264
TI  - Fluorescent analogues of myosin II for tracking the behavior of different myosin
      isoforms in living cells.
AB  - Fluorescently labeled smooth muscle myosin II is often used to study myosin II
      dynamics in non-muscle cells. In order to provide more specific tools for
      tracking non-muscle myosin II in living cytoplasm, fluorescent analogues of non
      muscle myosin IIA and IIB were prepared and characterized. In addition, smooth
      and non-muscle myosin II were labeled with both cy5 and rhodamine so that
      comparative, dynamic studies may be performed. Non-muscle myosin IIA was purified
      from bovine platelets, non-muscle myosin IIB from bovine brain, and smooth muscle
      myosin II from turkey gizzards. After being fluorescently labeled with
      tetramethylrhodamine-5-iodoacetamide or with a succinimidyl ester of cy5, they
      retained the following properties: (1) reversible assembly into thick filaments,
      (2) actin-activatable MgATPase, (3) phosphorylation by myosin light chain kinase,
      (4) increased MgATPase upon light-chain phosphorylation, (5) interconversion
      between 6S and 10S conformations, and (6) distribution into endogenous myosin II
      containing structures when microinjected into cultured cells. These fluorescent
      analogues can be used to visualize isoform-specific dynamics of myosin II in
      living cells.

PMID- 9518266
TI  - Identification and connections of inspiratory premotor neurons in songbirds and
      budgerigar.
AB  - Recordings of extracellular unit activity in the ventrolateral medulla and of
      electromyographic activity in either the M. scalenus, a principal inspiratory
      muscle, or the abdominal expiratory muscles, were used to identify inspiratory
      related (IR) neurons. IR neurons extended from levels caudal to the obex through
      the caudal level of the descending vestibular nucleus. This distribution was
      found to correspond to that of a subset of cells retrogradely labeled from
      injections of neuronal tracers into the upper thoracic spinal cord, where
      motoneurons innervating the M. scalenus were located by retrograde transport.
      Injections of biotinylated dextran amine at the recording sites resulted in
      projections to the spinal cord and brainstem. Bulbospinal axons traveled in the
      lateral funiculus, predominantly contralaterally, and terminated in relation to
      the dendrites and cell bodies of motoneurons innervating the M. scalenus.
      Brainstem nuclei receiving projections from injections at IR loci included the
      retroambigualis, tracheosyringeal motor nucleus, ventrolateral nucleus of the
      rostral medulla, infraolivaris superior, ventrolateral parabrachial nucleus, and
      the dorsomedial nucleus of the intercollicular complex. In the finches, there
      were also bilateral projections to nucleus uvaeformis of the posterior thalamus.
      The spinal and brainstem projections are similar to those found in pigeon (Reinke
      and Wild, [1997] J. Comp. Neurol. 379:347-362), and probably mediate the
      intricate coordination of the vocal (syringeal) and respiratory systems for the
      control of vocalization. The distribution of IR neurons in birds is similar to
      that of the rostral ventral respiratory group (rVRG) in mammals.

PMID- 9518267
TI  - Cat intraamygdaloid inhibitory network: ultrastructural organization of
      parvalbumin-immunoreactive elements.
AB  - Projection neurons of the basolateral (BL) amygdaloid complex are regulated by an
      intrinsic inhibitory network. To improve our understanding of this inhibitory
      circuit, we studied the synaptology of parvalbumin-immunopositive (PV+) elements
      as this calcium-binding protein is localized in a subpopulation of gamma
      aminobutyric acid (GABA)-ergic interneurons. Two populations of PV+ cells were
      identified on the basis of soma shape (ovoid, type A vs. polygonal, type B). In
      the lateral and BL nuclei, the majority of boutons in contact with PV+ cells
      formed asymmetric synapses (types 1-3; 94%), whereas a minority (type 4, 6%)
      established symmetric synaptic contacts and resembled GABAergic terminals. In
      both nuclei, type B PV+ perikarya were more densely innervated than were type A
      neurons. However, the pattern of synaptic innervation of type B PV+ neurons
      differed in the two nuclei: in the lateral nucleus, they were almost exclusively
      innervated by a population of small, presumed excitatory terminals (type 1),
      whereas the four categories of terminals contributed more equally to their
      innervation in the BL nucleus. PV+ boutons belonged to a single category of
      terminals that was enriched with GABA and formed symmetric synapses mostly with
      the proximal part of PV neurons. The proportion of axosomatic synapses was
      significantly higher in the lateral nucleus than in the BL nucleus (33% vs. 18%).
      The reverse was true for the contacts with proximal dendrites (33% in the lateral
      nucleus vs. 46% in the BL nucleus). The remaining terminals formed synapses with
      distal dendrites (23-28%) and spines (8-12%). These results indicate that PV+
      interneurons receive massive excitatory inputs and that PV+ terminals are
      strategically located to exert a powerful inhibitory control of amygdala neurons.

PMID- 9518268
TI  - Projection and innervation patterns of individual thalamic reticular axons in the
      thalamus of the adult rat: a three-dimensional, graphic, and morphometric
      analysis.
AB  - The gamma-aminobutyric acid-ergic thalamic reticular nucleus (Rt), which carries
      matching topographical maps of both the thalamus and cortex and in which
      constituent cells can synaptically communicate between each other, is the major
      extrinsic source of thalamic inhibitions and disinhibitions. Whether all the Rt
      axonal projections into the thalamus are similarly organized and have common
      projection and innervation patterns are questions of great interest to further
      our knowledge of the functioning of the Rt. The present study provides
      architectural and morphometric data of individual, anterogradely labeled axonal
      arbors that arose from distinct parts of the Rt. One hundred twenty-seven Rt
      neurons from all regions of Rt were marked juxtacellularly with biocytin or
      Neurobiotin in urethane-anesthetized adult rats. Eighteen two-dimensional and 14
      three-dimensional reconstructions of single tracer-filled Rt neurons were made
      from serial, frontal, horizontal, or sagittal sections. Both the somatodendritic
      and axonal fields of tracer-filled Rt cells were mapped in three dimensions and
      illustrated to provide a complementary stereotaxic reference for future studies.
      Most marked units projected to a single nucleus of the anterior, dorsal,
      intralaminar, posterior, or ventral thalamus. Axons emerging from cells in
      distinct sectors of the Rt projected to distinct nuclei. Within a sector, neurons
      with separate dendritic fields innervated separate regions either in a single
      nucleus or into different but functionally related thalamic nuclei. Neurons with
      an overlap of their dendritic fields gave rise either to overlapping axonal
      arborizations or, more rarely, to distinct axonal arbors within two different
      thalamic nuclei implicated in the same function. In rare instances, an Rt axon
      could project within these two nuclei. Thalamic reticular axons commonly
      displayed a single well-circumscribed arbor containing a total of about 4,000 +/-
      1,000 boutons. Every arbor was composed of a dense central core, which
      encompassed a thalamic volume of 5-63 x 10(6) microm3 and was made up of patches
      of maximal innervation density (10 +/- 4 boutons/tissue cube of 25 microm each
      side), surrounded by a sparse component. The metric relationships between the Rt
      axonal arbors and the dendrites of their target thalamocortical neurons were
      determined. Both the size and maximal innervation density of the axonal patches
      were found to fit in with the somatodendritic architecture of the target cells.
      The Rt axonal projections of adult rats are thus characterized by their (1) well
      focused terminal field with a patchy distribution of boutons and (2) parallel
      organization with a certain degree of divergence. The role of the Rt-mediated
      thalamic inhibition and disinhibition may be to contrast significant with
      nonrelevant ongoing thalamocortical information.

PMID- 9518269
TI  - Retinoid X receptor gamma gene transcripts are expressed by a subset of early
      generated retinal cells and eventually restricted to photoreceptors.
AB  - We have examined the distribution of the retinoid X receptor gamma (RXRgamma) in
      the developing chicken retina by using in situ hybridization and RNase protection
      assays. We detected RXRgamma transcripts as early as 4 days of embryonic
      development (d4) in central regions of the retina, spreading to more peripheral
      regions by d8. The first few RXRgamma-positive cells were scattered within the
      depth of the retinal neuroepithelium, but as they increased in number they became
      localized predominantly to the apical (outer, ventricular) layer. The identity of
      the RXRgamma-positive cells at these stages is unknown, due to the lack of cell
      type-specific markers. By d10, when photoreceptors and ganglion cells have been
      generated and begun to establish their definitive layers, RXRgamma-positive cells
      were virtually restricted to the photoreceptor layer, and maintained this
      distribution to posthatch stages. RNase protection assays were performed on whole
      retinae to verify the temporal pattern of in situ hybridization results and
      showed that between d5 and d16 there was a significant increase in the mRNA
      levels of the RXRgamma2 isoform. Between d16 and early posthatch stages the level
      of RXRgamma2 mRNA did not change significantly. Consistent with previous studies,
      mRNA levels of the RXRgamma1 isoform were substantially lower than mRNA levels of
      the RXRgamma2 isoform at all time points examined. These results demonstrate that
      RXRgamma mRNA is expressed in photoreceptors in the developing chicken retina and
      implicate RXRgamma as the earliest marker of photoreceptor differentiation
      documented to date.

PMID- 9518270
TI  - Anatomical relationships between aromatase and tyrosine hydroxylase in the quail
      brain: double-label immunocytochemical studies.
AB  - The activation of male sexual behavior in Japanese quail (Coturnix japonica)
      requires the transformation of testosterone to 17beta-estradiol by the enzyme
      aromatase (estrogen synthetase). There are prominent sex differences in aromatase
      activity that may be regulated in part by sex differences in catecholaminergic
      activity. In this study, we investigate, with double-label immunocytochemistry
      methods, the anatomical relationship between the catecholamine synthesizing
      enzyme, tyrosine hydroxylase (TH) and aromatase (ARO) in the quail brain. The
      immunoreactivity observed for each antigen generally matched the previously
      described distribution. One exception is the observation that cells weakly
      labeled for aromatase were found widely distributed throughout the telencephalon.
      The presence of telencephalic aromatase was confirmed independently by
      radioenzymatic assays. There was an extensive overlap between the distribution of
      the two antigens in many brain areas. In all densely labeled aromatase
      immunoreactive (ARO-ir) cell groups, including the preoptic medial nucleus,
      nucleus of the stria terminalis, mediobasal hypothalamus, and paleostriatum
      ventrale, ARO-ir cells were found in close association with TH-ir fibers. These
      TH-ir fibers often converged on an ARO-ir cell, and one or more TH-ir punctate
      structure(s) were found in close contact with nearly every densely labeled ARO-ir
      cell. In the telencephalon (mostly the neostriatum), all TH-ir fibers were found
      to be part of fiber groups that surrounded weakly immunoreactive aromatase cells.
      The few cells exhibiting an intracellular colocalization were detected in the
      anteroventral periventricular nucleus. These results are consistent with the
      hypothesis that catecholaminergic inputs regulate brain aromatase.

PMID- 9518271
TI  - Immunolocalization of aromatic L-amino acid decarboxylase, tyrosine hydroxylase,
      dopamine, and serotonin in the forebrain of Ambystoma mexicanum.
AB  - To improve basic knowledge about the neurochemical organization of the urodele
      brain, and to study discrepancies in the localization of monoaminergic markers,
      we immunohistochemically charted the distribution of four such markers (tyrosine
      hydroxylase, aromatic L-amino acid decarboxylase, dopamine, and serotonin) in the
      axolotl (Ambystoma mexicanum) forebrain. Catecholaminergic and serotoninergic
      systems were found in similar locations to those seen in other Urodela. As seen
      in other vertebrates, the localization of the different monoaminergic markers
      reveals some inconsistencies. Cells that are exclusively tyrosine hydroxylase
      immunoreactive are observed in the olfactory bulb, anterior olfactory
      nucleus/nucleus accumbens region, the epichiasmatic portion of the preoptic
      nucleus, and in the pars intercalaris thalami, whereas cells that are only
      labelled by aromatic L-amino acid decarboxylase are seen in the anterior
      olfactory nucleus/nucleus accumbens region, the bed nuclei of the anterior
      commissure, the posterior portion of the preoptic nucleus, the ventral
      hypothalamus, and the pars intercalaris thalami. The presence of cells solely
      serotonin (5-HT)-immunoreactive is suggested for the nucleus infundibularis
      dorsalis. Conversely, there were no areas that appeared to be exclusively
      immunoreactive for dopamine. Double-labelling for aromatic L-amino acid
      decarboxylase/tyrosine hydroxylase and aromatic L-amino acid
      decarboxylase/serotonin, together with cell counting, confirmed the existence of
      neurons that express only one monoaminergic marker in amphibian, supporting the
      hypothesis that these cells are universally present in the central nervous system
      of vertebrates.

PMID- 9518272
TI  - Few cholinergic neurons in the rat basal forebrain coexpress galanin messenger
      RNA.
AB  - The concept that galanin (GAL) is cosecreted with acetylcholine (ACh) into the
      ventral hippocampus is a major component of the current model delineating GAL
      regulation of the cholinergic memory pathways in the rat. Although GAL
      immunoreactivity coexists in 50-70% of cholinergic neurons in the basal forebrain
      (BF) of colchicine-treated rats, the actual coexistence of these
      neurotransmitters in the basal state may be lower, because colchicine treatment
      was recently shown to both induce GAL gene expression and inhibit choline
      acetyltransferase (ChAT) gene expression in this brain region. We have used
      single and double in situ hybridization histochemistry to examine the
      distribution and coexistence of GAL and ChAT mRNAs in the BF of male and female
      rats. Compared with other forebrain regions, few GAL mRNA-expressing neurons are
      present within the cholinergic fields of the BF. The greatest number of GAL mRNA
      expressing cells in this region are located within the nucleus of the horizontal
      limb of the diagonal band; but, even in this region, they represent only a small
      percentage (<20%) of ChAT mRNA-expressing cells. Our results indicate that few
      cholinergic neurons in the rat BF coexpress GAL mRNA and suggest that, in the
      basal state, GAL is not widely cosecreted with ACh into hippocampal memory
      centers.

PMID- 9518274
TI  - Proceedings of the Academy of Prosthodontics Halifax Symposium--Towards Optimized
      Management of the Edentulous Predicament. June 1997.

PMID- 9518275
TI  - Recent advances in gestational trophoblastic disease.

PMID- 9518276
TI  - Early medical social service at Mayo.

PMID- 9518273
TI  - Differential effects of autologous peripheral nerve grafts to the corpus striatum
      of adult rats on the regeneration of axons of striatal and nigral neurons and on
      the expression of GAP-43 and the cell adhesion molecules N-CAM and L1.
AB  - A segment of tibial nerve was autografted to the right corpus striatum of deeply
      anesthetized adult rats; the distal graft was left beneath the scalp. Horseradish
      peroxidase (HRP) conjugates were injected into the distal graft after 2-30 weeks,
      and the animals were killed 2-3 days later. Small numbers of neostriatal
      perikarya were HRP labeled at all survival times; most were large (ca. 20 microm
      in diameter), and many contained acetycholine esterase (AChE). Many more neurons
      were labelled in the substantia nigra pars compacta (SNpc) 4 weeks or more after
      grafting. When the graft encroached on the globus pallidus, numerous pallidal
      neurons, most of them AChE positive, were also labeled. Nigrostriatal neurons, a
      population of pallidal cholinergic neurons, and a subclass (or classes) of
      neostriatal neurons, including cholinergic interneurons, thus can be classified
      as central nervous system (CNS) neurons with a relatively strong regenerative
      response. In a second experimental series, animals were killed 1-4 weeks after
      grafting, and sections were probed for the expression of mRNAs encoding growth
      associated protein 43 (GAP-43) and the cell adhesion molecules N-CAM and L1.
      Subpopulations of mostly large neurons scattered throughout the neostriatum gave
      moderate signals for GAP-43 and N-CAM mRNAs and a stronger signal for L1 mRNAs.
      Most SNpc neurons were strongly labeled with all three probes. Neostriatal grafts
      had no apparent effect on the expression of any of the mRNAs in the SNpc or on L1
      and N-CAM mRNAs in the striatum. However, GAP-43 mRNA levels were increased in a
      few, mainly large neostriatal neurons around the graft tip, resembling the HRP
      labeled cells. In contrast, previous work has shown upregulation (from an
      undetectable level) of GAP-43 and L1 mRNAs in neurons regenerating axons into
      grafts placed in the thalamus and cerebellum. Thus, GAP-43 and L1 mRNA
      expression, but not necessarily marked upregulation, may correlate with, and be
      intrinsic determinants of, the ability of CNS neurons to regenerate their axons.

PMID- 9518277
TI  - Tetanus among injecting-drug users--California, 1997.
AB  - During 1997, 47 cases of tetanus were provisionally reported in the United
      States; 11 of these were reported from California. Of these 11, six (55%)
      occurred among injecting-drug users (IDUs). The substantial proportion of cases
      among IDUs prompted a review of reported tetanus cases in California. This report
      summarizes reported cases of tetanus in IDUs in California during 1987-1997 and
      presents two case reports for 1997.

PMID- 9518278
TI  - Administration of zidovudine during late pregnancy and delivery to prevent
      perinatal HIV transmission--Thailand, 1996-1998.
AB  - Worldwide, approximately 500,000 infants are perinatally infected with human
      immunodeficiency virus (HIV) each year, most of whom are born in developing
      countries. In 1994, a clinical trial in the United States and France demonstrated
      that zidovudine (ZDV) administered orally five times a day to HIV-infected
      pregnant women starting at 14-34 weeks' gestation, intravenously during labor,
      and orally to their newborns for 6 weeks reduced the risk for perinatal HIV
      transmission by two thirds. In 1994, this regimen was recommended as standard
      care in the United States; however, because of its complexity and cost, this
      regimen has not been implemented in most developing countries, and no other
      intervention had been efficacious in reducing perinatal HIV transmission. In
      1996, the Ministry of Public Health of Thailand and Mahidol University, in
      collaboration with CDC, initiated a randomized, placebo-controlled trial of a
      simpler and less expensive regimen of ZDV to prevent perinatal HIV transmission.
      This report describes preliminary trial results, which indicate that a short-term
      antenatal regimen of ZDV reduced the risk for perinatal HIV transmission by
      approximately half.

PMID- 9518279
TI  - HIV/AIDS among American Indians and Alaskan Natives--United States, 1981-1997.
AB  - A total of 641,086 cases of acquired immunodeficiency syndrome (AIDS) had been
      reported to CDC through December 1997. Of these, 1783 (0.3%) occurred in American
      Indians and Alaskan Natives (AI/ANs). AI/ANs represent <1% of the total U.S.
      population (272 million persons) and are characteristically diverse, comprising
      many tribes-of which 557 are federally recognized. Each tribe has its own
      traditions and culture. This report 1) describes characteristics of AI/ANs with
      AIDS reported to CDC through 1997; 2) summarizes trends in AIDS incidence among
      AI/ANs from 1986 to 1996; and 3) for the 25 states in which surveillance was
      conducted during 1994-1997 for human immunodeficiency virus (HIV) and AIDS,
      compares the characteristics of AI/ANs who had reported HIV infection (without
      AIDS) with those of AI/ANs who had AIDS. These findings, which highlight the
      characteristics of AI/ANs for whom HIV or AIDS had been diagnosed, can assist in
      the development of targeted prevention strategies.

PMID- 9518280
TI  - Mortality among children with sickle cell disease identified by newborn screening
      during 1990-1994--California, Illinois, and New York.
AB  - Sickle cell disease (SCD) is an autosomal recessive disorder characterized by
      production of abnormal (sickle) hemoglobin, resulting in anemia, susceptibility
      to pneumococcal and other infections, pain, stroke, and multiple organ
      dysfunctions. The most common types include hemoglobin SS (homozygous) disease,
      sickle cell-hemoglobin C disease, and the sickle beta-thalassemia syndromes. A
      randomized controlled trial published in 1986 indicated that daily oral
      penicillin prophylaxis reduced the incidence of serious infection in young
      children with SCD and led to widespread adoption of newborn screening programs
      for SCD. To study the effectiveness and utilization of prevention programs among
      large populations of infants with SCD, several newborn screening programs in the
      United States are now attempting to determine rates of complications and actual
      use of early medical interventions (e.g., penicillin prophylaxis and pneumococcal
      vaccination). This report focuses on recent mortality in California, Illinois,
      and New York. In California and Illinois, mortality from all causes among black
      children born during 1990-1994 with SCD was slightly less than overall mortality
      for all black children born in the same time period.

PMID- 9518282
TI  - Self-assessed health status and selected behavioral risk factors among persons
      with and without health-care coverage--United States, 1994-1995.
AB  - Persons without health-care coverage are more likely to have poor health and be
      at greater risk for chronic disease outcomes than persons who have health-care
      coverage. In the United States, the number of persons and the proportion of the
      population without health-care coverage has increased each year since 1987. State
      specific surveillance of health-care coverage can be used to identify subgroups
      of the population who lack such coverage and may be at increased risk for poor
      health. To determine state-specific estimates of the prevalence of self-assessed
      health status and risk factors for chronic disease by health-care coverage status
      among adults aged 18-64 years, CDC analyzed data from the 1994 and 1995
      Behavioral Risk Factor Surveillance System (BRFSS). This report summarizes the
      results of that analysis and indicates that adults without health-care coverage
      were more likely than those with health-care coverage to have poor health status,
      to be current smokers, and to be less physically active.

PMID- 9518281
TI  - Human exposure to Brucella abortus strain RB51--Kansas, 1997.
AB  - On May 26-27, 1997, nine persons (a farmer, four veterinary clinicians, and four
      veterinary students) in Manhattan, Kansas, participated in an attempted vaginal
      delivery, a cesarean delivery, and a necropsy on a stillborn calf that died
      because of Brucella abortus infection. The infection was confirmed by isolation
      of B. abortus from placental and fetal lung tissue cultures. The National Animal
      Disease Center, U.S. Department of Agriculture (USDA), identified the B. abortus
      isolate from the calf as the RB51 vaccine strain. RB51 is a live, attenuated
      strain that was licensed conditionally by the Veterinary Services, Animal and
      Plant Health Inspection Service, USDA, on February 23, 1996, for vaccination of
      cattle in the United States. Before 1996, vaccine was made by using the S19
      strain. This report describes occupational exposure to animals infected with the
      RB51 strain and emphasizes the need for surveillance of unintentional exposure of
      humans to RB51 to assess outcomes of such exposures.

PMID- 9518283
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 10-1998. A 46-year-old man with chest pain and coronary ostial
      stenosis.

PMID- 9518284
TI  - Hepatic dysfunction associated with troglitazone.

PMID- 9518285
TI  - Dietary fat intake and the risk of coronary heart disease in women.

PMID- 9518286
TI  - Dietary fat intake and the risk of coronary heart disease in women.

PMID- 9518287
TI  - Dietary fat intake and the risk of coronary heart disease in women.

PMID- 9518288
TI  - Cardiovascular medicine at the turn of the millennium.

PMID- 9518289
TI  - Cardiovascular medicine at the turn of the millennium.

PMID- 9518290
TI  - Recombinant hirudin compared with low-molecular-weight heparin to prevent
      thromboembolic complications after total hip replacement.

PMID- 9518291
TI  - Human papillomaviruses and anogenital cancer.

PMID- 9518292
TI  - Cutaneous melanoma metastases.

PMID- 9518293
TI  - Diarrhea associated with mesalamine in a patient with chronic nongranulomatous
      enterocolitis.

PMID- 9518294
TI  - Case 33-1997: a 75-year-old man with chest pain, hemoptysis, and a pulmonary
      lesion.

PMID- 9518295
TI  - Case 33-1997: a 75-year-old man with chest pain, hemoptysis, and a pulmonary
      lesion.

PMID- 9518296
TI  - Special issue dedicated to Dr. William T. Norton.

PMID- 9518297
TI  - Neurobehavioral Screening Methods. A report of the International Programme on
      Chemical Safety's Collaborative Study on Neurobehavioral Screening Methods.

PMID- 9518298
TI  - [Damage to the genome, p53 and cell polyploidization in ontogeny].
AB  - The protein p53 is a universal tumor suppressor in humans and negative regulator
      of cell proliferation, which is induced in cells in response to the damage of DNA
      and controls arrest of the cell cycle at specific checkpoints. A recently
      discovered function of gene p53 is the maintenance of the diploid state of the
      genome and a block of the formation of the population of cycling polyploids. This
      review examines models of disturbed control of the cell cycle due to loss,
      inactivation, or hyperexpression of gene p53 or its effector gene p21 in
      transgenic animals, i.e., homozygous mutant mice (p53-/-), (ERCC-1-/-), as well
      as in genetically defective cell lines in vitro. We discuss mechanisms
      responsible for the transition from the diploid to the polyploid state owing to
      the disturbed control of cell cycle by p53 and arising during the ontogenetic
      polyploidization of cells in normal animals.

PMID- 9518299
TI  - [The creation of genetic cryobanks and the use of the methods of developmental
      biology as a means for preserving rare animal species. III. The outlook, problems
      and limits: selection, modifications and mutations].
AB  - A review of our own and literature data about perspectives, problems and
      limitations in the use of cryoconservation techniques and methods of
      developmental biology for the conservation of genetic resources is presented. It
      is demonstrated that the use of these methods may result in the selection and
      possibly leads to modifications and mutations in germ cells and embryos and in
      this way may change the genetic structure of restored populations as compared
      with the original ones. The need to improve current techniques of
      cryoconservation and accompanying biotechnological procedures in order to abolish
      these undesirable genetic effects is emphasized.

PMID- 9518300
TI  - [A new class of small RNP (alpha-RNP) containing antisense RNA in K-562 cells.
      IV. The coordinated regulation of the expression of Alu-containing mRNA and alpha
      RNA during differentiation].
AB  - Small alpha-RNP of K-562 cells contain a small RNA as an RNA component, this RNA
      is homologous to Alu-repeating sequences of human DNA. When cells are exposed to
      dimethylsulfoxide, an agent inducing cell differentiation along the erythroid
      pathway, the content of both high-molecular-weight (heterogeneous nuclear and
      messenger) RNA enriched with Alu repeats and low-molecular-weight specific RNA,
      small Alu-homologous alpha-RNA undergoes a coordinated decrease. Using the
      technique of northern blot hybridization, we have demonstrated nonuniform
      distribution of Alu repeats both in the fraction of total low-molecular-weight
      RNA of the cytoplasm as well as in the fraction of messenger RNA. It is proposed
      that alpha-RNA (alpha-RNP) participates in the control of expression of non
      linked Alu-containing genes.

PMID- 9518301
TI  - [The nuclear scaffold structures and plasmid DNA replication in the cells of
      higher eukaryotes].
AB  - Incubation of purified plasmid DNA with nuclear matrix extracts enhances efficacy
      of DNA replication in Xenopus egg extracts. This enhancement correlates with the
      accelerated rate of pseudo-nuclei formation.

PMID- 9518302
TI  - [The organizational characteristics of the nucleolar region in the diploid and
      polyploid nuclei of neoplastic hepatocytes during dipin-induced carcinogenesis].
AB  - The use of the number of nucleoli as a criterion allowed us to identify
      significant differences in the organization of nucleoli in newly formed
      hepatocytes under the conditions of dipine-induced carcinogenesis 8-10 weeks
      after its initiation, as compared with normal liver cells of adult mice. The
      number of nucleoli in tetraploid new hepatocytes was equal to that in the diploid
      nuclei of normal liver (on average 3.5 and 3.6, respectively) and the number in
      the new octaploid nuclei was equal to that in tetraploid (6.2 and 6.4,
      respectively). A higher extent of association of nucleolar organizers under the
      conditions of endoreproduction or the association of homologous chromosomes in G1
      period of the cell cycle is discussed as a possible mechanism responsible for the
      decrease in the number of nucleoli.

PMID- 9518303
TI  - [NO synthetase in the cells of different tissues and organs of the mouse].
AB  - Cellular NO synthase was assayed in bone marrow, spleen, thymus, lymph nodes,
      epidermis, hypodermic connective tissue, small gut, peritoneal exudate, liver,
      kidney, and heart by cytochemical and immunofluorescent methods. As a rule the
      enzymatic activity was found in differentiated cells that finished proliferation
      (mature hemopoietic cells, epithelium of gut villi, etc.). The enzyme activity
      was undetectable in actively reproducing low-differentiated cells (basal layer of
      the epidermis, crypt cells of the small gut, or blast hemopoietic forms). NO is
      proposed to participate in regulation of tissue-specific terminal differentiation
      (maturation) of the cells.

PMID- 9518305
TI  - [The 30th anniversary of the Institute of Developmental Biology and the 80th of
      the Institute of Experimental Biology].

PMID- 9518306
TI  - [How was Polish phoniatrics born? (Part III. Jan Siestrzynski, Jozef Frank)].
AB  - The last years of Jan Siestrzynski (1788-1824), the first Polish phoniatrist, as
      a military physician at Konskie are presented. Siestrzynski was the author of a
      book of "Teorya i mechanizm mowy..." ("Theory and Mechanism of Speech..."),
      published in 1820. This book was the fundamental work of his life. The
      publications by Trompeo (1820), Borthwick (1836) and Bruck (1856) dealing with
      similar problems dated later made Siestrzynski one of the first pioneers of
      European phoniatrists. Siestrzynski's book "O litografii" ("On litography" is
      briefly presented. The achievements of Jozef Frank (1771-1842), who was a
      professor of Vilnius University, in popularization of the knowledge about speech
      disorders (especially in his book "Praxeos medicae universae praecepta" were
      pointed out).

PMID- 9518304
TI  - [The effect of 5-bromo-2'-deoxyuridine on the lifespan and behavior of Drosophila
      melanogaster].
AB  - In this study, we have examined the effect of 5-bromo-2'-deoxyuridine
      incorporated into DNA of Drosophila nerve cells after incubation of larvae in the
      analog-containing medium on the duration of lifespan and behavior (photoactivity)
      of adult flies. 5-Bromo-2'-deoxyuridine incorporated into DNA decreases the
      lifespan of adult animals. In contrast to the control, the curves describing the
      probability of death become bimodal at higher doses of the analog (above 35
      (g/ml). As the dose of 5-bromo-2'-deoxyuridine decreases, photoactivity of the
      flies diminishes, and the distribution into fractions with different activity
      becomes broader. The data obtained provide evidence that the modification of DNA
      with 5-bromo-2'-deoxyuridine drastically changes the expression of tissue
      specific genes in nerve ganglia of Drosophila and at the same time diminishes the
      duration of insects lifespan. These observations suggest that genome of the nerve
      cells appears to be a probable initial substrate of Drosophila aging.

PMID- 9518307
TI  - [Salvage surgery after unsuccessful radiotherapy of laryngeal cancer].

PMID- 9518308
TI  - [Sensorineural hearing loss and atheromatosis. Risk factors].

PMID- 9518309
TI  - [Efficiency of surgical treatment in patients with laryngeal cancer depending on
      age].
AB  - In the group of 578 patients with larynx cancer that underwent surgical treatment
      in four clinics of Medical Academies between 1986-87 a comparable analysis of the
      efficiency of surgical treatment depending on age of the operated patients was
      carried out. It was found that the difference between age average and the general
      state of patients was statistically highly important: Statistically significant
      was also the dependence between the patients' age and the postoperative
      complications; close to importance was also the dependence between the age and
      the survival period of patients. 68% of operated patients up to 65 year of age
      had five-year survival period without any symptoms; but in the group of patients
      over 65 years of age the analogical survival value was 51%.

PMID- 9518311
TI  - [Endoscopic sinus surgery: surgical technique].

PMID- 9518310
TI  - [The role of radiotherapy in the management of benign lymphoepithelial lesions].
AB  - Benign lymphoepithelial lesion (BLL) is observed as a diffuse or nodular
      enlargement of major salivary gland. In 80% it appears in woman in the sixth and
      seventh decade. The histopathologic appearance consist of a triad of
      parenchymatous atrophy, interstitial lymphocytic infiltration and
      epimyoepithelial islands. This disease co-exists in 50% of cases with connective
      tissue disorders. In patients with BLL the risk of the development of a malignant
      lymphoma may be as high as 40:1 in comparison to the control group. From 1960 to
      1991 ten women with BLL in salivary glands were treated in Oncology Centre in
      Krakow. The disease was localized in parotid glands (8 pts), in submandibular
      glands (1 pt) and in parotid and submandibular gland (1 pt). In this group 3
      patients were treated for the rheumatoid arthritis and in 1 women presented
      symptoms of Sjogren' syndrome. Exclusive surgical treatment was performed in 2
      patients, 7 patients were treated with irradiation, and 1 patient received
      combined therapy: surgery and radiotherapy. The doses of irradiation were from 12
      to 36 Gy given in 6 to 18 fractions. Complete remission was observed in 2
      patients who received only surgical treatment. In group of 8 patients treated
      with irradiation and surgery and irradiation we have observed local control in
      six women after 1 series and in two women after 2 series of irradiation. During
      the observation malignancies developed in 4 patients between 11 to 39 months
      after radiotherapy. One patient developed cancer of salivary gland. In remaining
      3 patients it was observed malignant lymphomas. Our results of therapy of BLL in
      salivary gland are similar to presented by the other authors and indicate the
      efficiency of local (surgical or irradiation) treatment.

PMID- 9518313
TI  - [The prognostic significance of impaired vocal cord motility in patients with
      stage II glottic cancer treated with radiotherapy].
AB  - Eighty-five patients with stage II glottic laryngeal cancer were treated with
      radiotherapy in Center of Oncology in Krakow between 1973 and 1989. Fifty-five
      patients were irradiated with 60Co unit, 30 with mixed photon--electron beam. The
      5-year survival rates without evidence of disease after the radiotherapy only
      were 65.9%, after the radiotherapy and surgery for recurrences--76.5%. The sex,
      age, local extension of primay tumour and vocal cord mobility were evaluated in a
      uni- and multivariate analysis of prognostic factors. For the end-point of 5-year
      survival without evidence of disease no statistically significant relationship
      was found between results and analysis variables, especially between survival and
      impaired cord mobility.

PMID- 9518312
TI  - [Microsurgical treatment of laryngeal papillomatosis].
AB  - Authors present distant results of treatment in 15 patients with laryngeal
      papillomatosis between 11 and 21 years of age treated from 1975 to 1994 in Warsaw
      ENT Clinic for Children by microsurgery m. Kleinsasser. The course of disease,
      methods of treatment, ending treatment age present voice function plus other
      conditions of larynx was analysed. The current therapy and advantages of
      microsurgical treatment used in our Clinic in patient with laryngeal
      papillomatosis (papillomatosis juvenile) has been showed. In the estimate group
      at 11 patients good function of fonation was as follow up confirmed. It was
      confirmed that this treatment is successful. The long term fonations results
      after microsurgery m. Kleinsasser appear in our opinion better then after laser
      therapy. It appear in future the best therapy should be a pharmacological
      treatment.

PMID- 9518314
TI  - [The influence of the duration of a break in the course of postoperative
      radiotherapy on the results of treatment of patients with total laryngectomy due
      to cancer].
AB  - The analysis of survival of 311 patients after total laryngectomy due to cancer
      and conventional postoperative radiotherapy was performed. During irradiation in
      a part of patients were introduced interruptions in treatment and no related
      diseases. The gap in treatment was taken in account and for this factor all
      patients were divided into 3 groups; without gap in treatment (A), with short gap
      -below 7 days (B) and with long gap--over 7 days (C). All groups were comparable.
      It was concluded that the long gaps increase the failure in treatment for about
      30%.

PMID- 9518315
TI  - [Modified method of pharyngeal occlusion after laryngectomy using lingual flap].

PMID- 9518316
TI  - [Rhinitis medicamentosa: an increasing therapeutical problem].
AB  - The most common upper respiratory illness is rhinitis. The majority of ENT
      specialists and general practitioners prescribe topical decongestants as first
      line therapy in rhinitis, independently of causes and kind of rhinitis. Long term
      use of topical vasoconstrictors for the nose may result in rhinitis
      medicamentosa, the rebound swelling of the nasal mucosa. The swelling probably is
      due to vasodilatation, but it may be also due to interstitial oedema. The
      prolonged use of decongestants may destroy the nasal cilia and mitochondria of
      epithelial cells, disturbing their function. Rhinitis medicamentosa from topical
      vasoconstrictor abuse results in nasal obstruction which can be life-threatening
      in neonates. Rhinitis medicamentosa is a increasing therapeutical problem that is
      best managed by prevention.

PMID- 9518317
TI  - [The evaluation of certain psychological indices concerning cognitive and
      emotional behaviors in patients after radical neck dissection].
AB  - Every disease and especially neoplasmatic disease is a source of deep mental
      experiences. The aim of this study was the establishment of some psychological
      behavioural parameters in 55 patients who underwent radical neck dissection and
      in 32 patients operated for other, non-neoplasmatic laryngologic diseases. In
      order to evaluate psychological state of the patients the following of States and
      Personality Traits (TISCO), 2. Feeling of Safety Question Sheet (KPB), 3. Profile
      of Mood States (POMS), 4. Scale of Hopelessness (HS-8). It was stated, that
      patients after radical neck dissection have deviations concerning indexes of
      cognitive and emotional behaviour and that there are differences between patients
      operated as the reason of neoplastic processes and other patients. These
      differences appear also among persons examined in the period shorter than 1 year
      from their surgery as opposed to patients operated earlier than 1 year before
      examinations. The fact of laryngectomy did not appear to have significant
      influence upon most of the evaluated indexes of cognitive and emotional
      behaviours.

PMID- 9518318
TI  - [The evaluation of the phase angle in the tympanometric examination of the middle
      ear in a healthy population].
AB  - The results of phase angle estimations in 62 middle ears in healthy peoples were
      presented. Examinations were performed using multifrequency middle ear analyser
      with probe tone frequency from 250 to 2000 Hz. Own laboratory norms were
      estimated for the peak value and phase angle value in resonance frequency of
      middle ears. Obtained results were compared with other authors examinations. No
      significant statistical corellations between peak value of phase angles and probe
      tone frequency of impedancemeter were found.

PMID- 9518319
TI  - [Vestibular evoked potentials in people].
AB  - In the article had been presented the structure and functioning of a prototype
      system for stimulation and registration vestibular evoked potentials, and the
      first recording of evoked vestibular potentials (VsEPs) in human beings. This
      system consist of a original stimulator accelerated for the stimulation of
      vestibular organ, modul registratory VsEPs as well as string elements and
      synchronizing stimulation with recording. IMB PC 486 is quickly process of
      investigation with help of standard interface and a original computer programme.
      Vestibular organ had been evoked by 200 to 500 cyclicly repealed angular
      decelerations of 4000 degrees/s2. During investigation white noise was used for
      masking to avoid the evoking of auditory potentials. Seven of the examined
      healthy persons (including one deaf person whose vestibular organ was not
      damaged) had registered a response consisting of several waves with vertex
      positive peaks. The first two waves P1 and P2 with the mean value 2.02 ms and 5.6
      ms are most often during in the 10 ms. The registered deaf persons response does
      not differ from the record of healthy persons.

PMID- 9518320
TI  - [Congenital nystagmus with sensory disorder: reaction to the caloric and
      optokinetic stimulation].
AB  - The purpose of this study was to estimate the response on vestibular caloric and
      optokinetic stimulation in patients with congenital nystagmus and serious
      congenital anomalies of visual system. 58 patients, aged 11-20 (21 female, 37
      male) underwent this stimulation with ENG registration. The patients had visual
      acuity from 0.04 to 0.4, caused by visual system diseases e.g. congenital
      cataract, optic atrophy, hypoplasia maculae, high refractive error, albinism ect.
      The correct response was observed with 15.5% of the patients on vestibular
      caloric stimulation. There was no statistically significant relationship between
      visual acuity or visual system disease and the correct response. 28% of the
      patients responded correctly on optokinetic stimulation. There was statistically
      significant relationship between visual system anomaly and correct OKN: 80% of
      this reaction was in the group of optic atrophy, 54% in the group of high
      refractive error. Statistically significant relationship was no observed between
      visual acuiy and correct OKN. High level of the incorrect response on the caloric
      and optokinetic stimulation in the persons with congenital nystagmus and
      congenital disorder of visual system limits using of this tests for diagnostic
      purpose.

PMID- 9518321
TI  - [Isotopic studies on the regeneration of stapedial bone in otosclerosis].
AB  - The aim of the study was determining the bone rebuilding activity in stapes and
      otosclerotic focus and comparison the relation between bone rebuilding activity
      with some clinical features such as the patient's sex and age, duration of the
      disease and the degree of hearing impairment. The study covered 98 patients aged
      from 18 to 68 years (X = 37 years) in whom, due to otosclerosis, stapedectomy was
      performed at the Clinic of Otolaryngology--PAM in Szczecin. The rebuilding
      activity was estimated in bone fragments having been removed during the
      operation, i.e. in 98 specimens of canal wall bone, 97 specimens of stapedial
      crura, 88 fragments from posterior and 18 fragments from anterior parts of
      footplate as well as in 15 otosclerotic foci, using isotopic method implementing
      a complex of pyrophosphate labelled with technetium Tc-99m. The degree of bone
      rebuilding activity was defined by the amount of absorbed isotopic index. The
      "control group" was made up of 9 cases, in which stapedectomy was carried out for
      therapeutical purpose in consequence of other ailments, namely: in 3 cases of
      congenital stapedial ankylosis, 5 cases of stapedial tympanosclerosis, and 1 case
      of Menier's disease. It has been disclosed that otosclerosis is an active
      pathological process, involving the bone of the entire stapes with the strongest
      manifestation in the disease focus. An essential fact was linked with the very
      low bone rebuilding activity in the stapedial footplate and crura in the "control
      group". The bone rebuilding activity in otosclerotic foci and footplate of stapes
      was somewhat higher in males than in females. It was the highest in patients
      whose disease duration was the longest. In general the bone rebuilding activity
      didn't influence the degree of hearing impairment.

PMID- 9518322
TI  - [Actinobacteriosis of paranasal sinuses].
AB  - On the base the review of literature and own case the authors presents diagnostic
      difficulties and therapy of paranasal sinuses actinobacteriosis.
      Actinobacteriosis of sinuses is very rare case and diagnostic analysis based on
      mycologic and histopathologic investigations. In our case sinuses
      actinobacteriosis orbital abscess complication has been noted. Antibiotic therapy
      and surgical treatment have been used in this case.

PMID- 9518323
TI  - [Clinical investigations and cytological examinations of the nose in subject
      exposed to cement dust].
AB  - Mucous membranes of the nose of 90 persons exposed to cement dust were
      investigated clinically and cytologically. We found atrophic changes in 37.8%
      persons and hypertrophic changes in 13.3%. In a halt of the investigated persons
      abnormality in epithelium forms in cytological examination was demonstrated. The
      connection of inflammatory changes and pathological forms of the epithelium has
      been documented. The correlation between presentation of cement deposits and
      inflammatory infiltrations and atrophic and hypertrophic changes was confirmed.

PMID- 9518324
TI  - [Is gender a prognostic factor in early stages of laryngeal cancer treated by
      radiotherapy?].
AB  - Six hundred and thirty patients with stage I and II glottic and supraglottic
      laryngeal cancer were treated with radiotherapy in Center of Oncology in Krakow
      between 1973 and 1989. The 5-year NED survival rates after the radiotherapy only
      were 79%, after the radiotherapy and surgery for reccurrences--87.1%. Gender is
      not a prognostic factor in early stage laryngeal cancer treated with
      radiotherapy.

PMID- 9518325
TI  - [Prognostic factors in patients with early stages of supraglottic cancer treated
      by radiotherapy].
AB  - Three hundred patients with early stage supraglottic cancer were treated with
      radiotherapy in Center of Oncology in Krakow between 1973 and 1989. The 5-year
      NED survival rates after the radiotherapy only were 82.9% in stage I, and 70%in
      stage II cancer, after the radiotherapy and surgery for recurrences--90% and 75%
      respectively. The stage and tumor site were an important prognostic factors in
      the treated group of patients.

PMID- 9518326
TI  - [Influence of the anatomical structure of the uncinate process on bone patency of
      the maxillary sinus: a radiological and clinical evaluation].
AB  - The group of 185 patients with chronic and acute recurrent rhinosinusitis was
      analyzed radiologically with CT scans. The anatomical structure of the uncinate
      in its upper part, configuration and position of its low margin were evaluated.
      The results have been compared to the normal CT scans of paranasal sinuses of 50
      persons without any sinus disease. The significant correlation was found between
      the shape and the development of pneumatization of the turbinate and the
      configuration of the uncinate process as well as to its type. The degree of the
      pneumatization and configuration or hypertrophy of the turbinate correlate also
      to the maxillary sinus disease.

PMID- 9518327
TI  - [The results of treatment of esophageal burns admitted to the 2nd ENT clinic in
      Zabrze].
AB  - The authors presented a 4 cases of esophageal scar tissue stenosis due to burns.
      The results of treatment in 3 patients were successful. One patient needs
      periodical dilatation. Therapeutic problems were discussed.

PMID- 9518328
TI  - [The incidence of peculiar IgE in response to inhalant allergens in relation to
      the age of the patient].
AB  - 208 patients between the age of 1 month to 56 years, with symptoms of respiratory
      tract allergy were investigated. In all cases serum titre of sIgE to birch,
      thymoty, rye, mugwort pollen, Alternaria Alternata, dog, cat fur,
      Dermatophagoides pteronyssinus and farinae was determined with the use of Quidel
      immunoenzymatic method. We have found sIgE to Alternaria Alternata in 8 (38%),
      birch pollen in 5 (23.8%) dog fur in 5 (23.8%) and thymoty and rye pollen in 3
      (14.3%) even among one years-old infants. In the second and third years of life
      allergy to dog fur, Alternaria Alternata and pollen of birch, thymoty and rye
      increases while the age of 4 and 5 is less significant, later (6-10 years old
      patients) increases again. Among teenagers pollinosis gets decreases and adults
      have development constant level of the disease.

PMID- 9518329
TI  - [Ocular and orbital symptoms of Wegener's disease].
AB  - Wegener's granuloma occurs most commonly in upper respiratory tract, in lungs and
      in kidneys. In many cases ocular and orbital disturbances may be accompanied by
      changes in the nose and sinuses. These disturbances occur as: superior orbital
      fissure syndrome, orbital apex syndrome or ocular fascicle atrophy. The authors
      present the symptoms of these disturbances in 3 patients treated at
      Otolaryngological Clinic, Medical University of Gdansk. On the bases of clinical
      symptoms and radiological results (CT and MRI) the assessment of pathogenesis of
      ocular and orbital symptoms was made in each of these cases, with special regard
      to the mode and result of the treatment.

PMID- 9518330
TI  - [Changes in vascularization of sternocleidomastoid myocutaneous flaps].
AB  - Studies of variation in the vascularisation of the sternocleidomastoid
      myocutaneous flap. An investigation of vascularisation of the sternocleidomastoid
      myocutaneous flaps was conducted. The research was performed on human cadavers
      and after injection of arteries 40 myocutaneous flaps of sternocleidomastoid
      muscle were isolated. The experiment was performed to investigate the origin of
      the arteries vascularising the muscle and the area of skin, which were used to
      make the myocutaneous flaps. Changes are characteristic in the lower 2/3 parts of
      the muscle. These variables may exert an important influence of the outcome of
      reconstruction treatment in the case of the flaps used from the lower attachment
      of the muscle.

PMID- 9518331
TI  - [Content of fluoride and calcium in stapedial bone in otosclerosis].
AB  - The study dealing with the content of fluoride and calcium in stapedial bone and
      canal wall bone in otosclerosis was performed in 69 subjects (48 females and 21
      males) out of the patients, in whom bone rebuilding activity had earlier been
      studied isotopically. The control group comprised 20 normal stapedies taken
      during autopsies. Fluoride content was determined by means of fluoride ions
      meter, the content of calcium was assessed by resorting to atomic absorptiometer.
      The content of studied elements was compared with the bone rebuilding activity
      and some clinical features such as the patient's age and duration of the disease.
      High fluoride content in otosclerotic stapes was revealed, being several times
      greater than in the bone of normal stapes. Concurrently the stapedial bone in
      otosclerosis contained less calcium as compared with the bone of normal stapes.
      In principle, that referred to otosclerotic focus and next to stapedial crura.
      The bones of stapedial footplates and otosclerotic foci with rebuilding activity
      lover han the means value had statistically significant, higher content of
      fluoride and calcium than the bones with greater rebuilding activity. Fluoride
      content in stapedial bone during otosclerosis dramatically increased with the
      patient's age and the length of the disease duration period, however, the calcium
      content had the tendency to decrease.

PMID- 9518332
TI  - [Voice pathology in patients with allergic rhinitis].
AB  - The aim of work was evaluation of voice pathology in patients with allergic
      rhinitis. Larynx organic pathology were found in 75% patients with coexisting
      allergic rhinitis in the form of Reinke's oedema, chronic hypertrophic
      laryngitis, larynx polyp and vocal nodules. It caused serious voice pathology
      (dysphonia) which was confirmed by an objective spectrographic method. Larynx
      organic pathology was not in 15% patients. In these cases rhinophonia was found
      in consequence of resonance nasal defect.

PMID- 9518333
TI  - [Effect of surgical treatment of otitis media with effusion on children. Personal
      experience].
AB  - The authors present their observations upon surgically treated children with
      otitis media with effusion. The results are indicative of usefulness of
      ventilation tubes, myringotomy and adenoidectomy in the treatment of the otitis
      media with effusion in children. The efficiency of the treatment is based on the
      hearing examination and tympanometry, and the lack of recurrence of inflammation
      of the middle ear. 67.6% of cases revealed normal hearing.

PMID- 9518334
TI  - [Psychophysical and objective investigation of hearing in presbyacusis].
AB  - In 30 individuals aged 50 to 82 the following audiologic examinations were
      performed: tonal audiometry (air/bone conduction), impedance audiometry
      (tympanometry and registration of stapedius reflex to pure tone of 0.5-4 kHz and
      noises) and ERA tests after acoustic stimulation from different levels of the
      hearing pathway (BERA, MLR and SP). The assessment of the results showed:--1. the
      threshold values in the objective methods are proportional to those obtained in
      tonal audiometry;--2. in ERA an interpersonal lability of latencies at different
      levels of the hearing pathway was observed including shortening, elongation and
      normal values;--3. in 70% of the examined aged 50-82 SRT were below 70 dB SL and
      loudness sumation below 25 dB;--4. shortening of the SP latencies was in 100%
      correlated to the low values of the loudness summation and recruitment found in
      psychophysical examinations.

PMID- 9518335
TI  - [Class I HLA antigens in patients with sensorineural hearing loss: preliminary
      report].
AB  - The frequency of class I HLA antigens of 36 sensorineal hearing loss patients
      with bilateral, progressive and sudden deafness were analyzed. It was found that
      HLA-B41 and HLA-Cw7 were more frequent than in 1152 control population (Chi2=
      1656 and 14.45 respectively). The differences were highly significant (p < 0.001)
      The homozygosity of HLA-Cw/Cw7 in examined patients was also statistically
      different in comparison with 616 healthy individuals (p < 0.025). Determination
      of soluble form class I HLA antigens (s-HLA-I) in semiquantitative method
      according to Tait et al. (1981) and McLean et al. (1983) was performed. In 24 of
      sera SNHL patients and in 126 healthy persons the level of sHLA-Cw7 was examined.
      The preliminary results show that distribution of soluble Cw7 antigen in patients
      sera and healthy controls were significantly decreased in cases of SNHL (Ch2 =
      28.23; p < 0.0001). The authors suggest an existing relationship between SNHL and
      sHLA-Cw7, Further study may resolve this relation and possibilities of monitoring
      sHLA-Cw7 during therapy and course of this disease.

PMID- 9518336
TI  - [The auditory brainstem response recordings in small children at night].
AB  - Authors compare two methods of hearing assessment using ABR recordings in
      children at the age of 1 to 6 years. Following are the applied methods: 1) ABR
      recording in natural sleep at night and 2) ABR recording in pharmacologically
      induced sleep. Advantages and disadvantages of the methods are presented and
      parameters such as: time of examination, number of averages, number of artefacts
      and percentage of successful recordings have been evaluated.

PMID- 9518338
TI  - [Chemodectoma of the nasal cavity and paranasal sinuses].
AB  - A rare case of chemodectoma of the nasal cavity and paranasal sinuses is
      presented. Chemodectoma are unusual tumours arising in specialized tissue
      probably of neural cres origin. The patient underwent surgery with total removal
      of the tumour. The presence of such a tumour raises questions as to the origin of
      such specialized tissue within the nose and paranasal sinuses.

PMID- 9518337
TI  - [The case of myoepithelioma of the parotid gland].
AB  - Myoepithelioma of the parotid gland occurs relatively rarely. In the literature
      was described only 33 cases of this tumors. It's growth's slow and distension.
      Basing upon the case of 48-year old woman, the authors discuss the difficulties
      of diagnostic, treatment and the course of the disease.

PMID- 9518339
TI  - [A case of lymphoepithelioma of the larynx].
AB  - The very rare case of lymphoepithelioma of the larynx was presented. The opinions
      on the histogenesis of such tumors as well as histopathologic terminology were
      shown. The patient was successfully treated by radiotherapy.

PMID- 9518340
TI  - How to evaluate a dental provider contract.

PMID- 9518341
TI  - Europace '97. Athens, Greece, June 8-11, 1997. Proceedings.

PMID- 9518342
TI  - Nurses manage recombinant interleukin-2 side effects in elderly patients with
      leukemia.

PMID- 9518344
TI  - Measurement tool documents clinical workload of advanced practice nurses in
      cancer care.

PMID- 9518343
TI  - Facility raises awareness of ambulatory and hospitalized patients' pain reports.

PMID- 9518345
TI  - Rural oncology outreach program requires special nursing education.

PMID- 9518346
TI  - Ab initio protein folding simulations with genetic algorithms: simulations on the
      complete sequence of small proteins.
AB  - Ab-initio folding simulations have been performed on three small proteins using a
      genetic algorithm- (GA-) based search method which operates on an all atom
      representation. Simulations were also performed on a number of small peptides
      expected to be independent folding units. The present genetic algorithm
      incorporates the results of developments made to the method first tested in
      CASP1. Additional operators have been introduced into the search in order to
      allow the simulation of longer sequences and to avoid the simulation of longer
      sequences and to avoid premature free energy convergence. Secondary structure
      information derived from a consensus of eight methods and Monte Carlo simulations
      on sets of homologous sequences has been used to bias the starting populations
      used in the GA simulations. For the fragment simulations, the results generally
      have approximately correct local structure, but tend to be too compact, leading
      to poor RMS error values. One of the three small protein structures has the
      topology and most of the general organization correct, although many of the
      details are incorrect.

PMID- 9518347
TI  - Treatment of psychosis with prochlorperazine in the ICU setting.

PMID- 9518348
TI  - [Genome science--aiming for new life science (discussion)].

PMID- 9518350
TI  - The environmental syndrome--psychosomatic disease experience induced by
      environmental factors. Proceedings of the XII Signe and Ane Gyllenberg Symposium.
      Espoo, Finland, September 28-29, 1995.

PMID- 9518349
TI  - Measuring attentional demand in continuous dual-task performance.
AB  - Despite its intuitive appeal, the commonly held assumption that there is some
      general limitation on dual-task performance has been shown to be seriously flawed
      (Allport 1980; Navon 1984). Central to this has been the inability to measure the
      attentional demands of tasks, without which there is no way to determine whether
      their joint demands exceed the hypothetical general limit. In the absence of such
      a measure, dual-task interference can always be explained by the alternative
      possibility that specific interference has occurred. A method is described in
      which the attentional demands of tasks can be measured and cross-validated by the
      use of two scales. Two experiments are described in which a general attentional
      limit is found; the measurement of attentional demand is consistent across scales
      and can be made at a level of precision approximating that of an interval scale.

PMID- 9518351
TI  - Bison study principal investigator.

PMID- 9518352
TI  - Privatization of a journal.

PMID- 9518353
TI  - Privatization of a journal.

PMID- 9518354
TI  - Privatization of a journal.

PMID- 9518355
TI  - On the antibiotic frontier.

PMID- 9518356
TI  - Clinton backs broad genetic safeguards.

PMID- 9518357
TI  - Global initiative takes shape slowly.

PMID- 9518358
TI  - Is an old virus up to new tricks?

PMID- 9518359
TI  - Yeast protein acting alone triggers prion-like process.

PMID- 9518360
TI  - Comet origin of oceans all wet?

PMID- 9518361
TI  - Hijacking a cell's chemical paths to make new antibiotics.

PMID- 9518362
TI  - Water on the sun: molecules everywhere.

PMID- 9518363
TI  - GAP into the breach.

PMID- 9518364
TI  - How does the brain organize memories?

PMID- 9518365
TI  - Antigen presentation: a balanced diet.

PMID- 9518366
TI  - Genetic complexity and Parkinson's disease. Deane Laboratory Parkinson Disease
      Research Group.

PMID- 9518367
TI  - Genetic complexity and Parkinson's disease.

PMID- 9518368
TI  - Experiments in a Parkinson's rat model.

PMID- 9518369
TI  - After the genome database.

PMID- 9518370
TI  - NMR availability.

PMID- 9518371
TI  - Early education of the deaf.

PMID- 9518372
TI  - Lawsuit targets Yellowstone bug deal.

PMID- 9518373
TI  - Celebrated virus hunters set up shop in France.

PMID- 9518374
TI  - New role for estrogen in cancer?

PMID- 9518375
TI  - Did the first complex cell eat hydrogen?

PMID- 9518376
TI  - Mapping the sensory mosaic.

PMID- 9518377
TI  - A bridge to control.

PMID- 9518378
TI  - Risk factors for human immunodeficiency virus infection and unprotected anal
      intercourse among young men who have sex with men.
AB  - BACKGROUND AND OBJECTIVES: Few studies concerning human immunodeficiency virus
      (HIV) and its risk behaviors have been conducted among young men who have sex
      with men (YMSM). These are important because YMSM will have profound influence on
      the HIV/acquired immunodeficiency syndrome epidemic. GOALS: To estimate the
      prevalence of and risk factors associated with HIV infection and recent
      unprotected anal intercourse (UAI) among YMSM in California. METHODS: Between
      March and October, 1994, 836 men, 17 to 25 years of age, were surveyed at four
      California sites. The survey consisted of an interview from a standardized
      questionnaire and a blood draw for HIV antibody testing. RESULTS: Almost 9.0%
      tested positive for HIV antibodies, whereas about 36.0% reported recent UAI.
      Several factors were associated both univariately and multivariately with HIV
      infection, as well as for recent UAI. CONCLUSIONS: Young men who have sex with
      men in California continue to engage in behaviors risky for HIV infection.
      Efforts helping YMSM reduce them should target subgroups having a high HIV
      seroprevalence or recent UAI prevalence.

PMID- 9518379
TI  - Screening women for chlamydia trachomatis in family planning clinics: the cost
      effectiveness of DNA amplification assays.
AB  - BACKGROUND: Highly sensitive and specific DNA amplification assays are available
      for use on cervical and urine specimens. These new tests have the potential to
      identify more chlamydial infections than the commonly used enzyme immunoassay and
      DNA probe tests, yet they are more expensive. This study sought to assess the
      cost effectiveness of cell culture, enzyme immunoassay (EIA), DNA probe (Pace 2),
      polymerase chain reaction (PCR) of cervical and urine specimens, and ligase chain
      reaction (LCR) of cervical and urine specimens as screening tools for Chlamydia
      trachomatis in asymptomatic women younger than 30 years of age attending family
      planning clinics. STUDY DESIGN: Program costs; medical cost savings of prevented
      sequelae in women, male sex partners, and infant; and number of prevented cases
      of pelvic inflammatory disease (PID), neonatal infections, and male sex partner
      urethritis and epididymitis were modeled in a decision analysis conducted from a
      health care system perspective. Results are expressed for a cohort of 18,000
      women. RESULTS: If no screening for C. trachomatis were conducted in Maryland,
      497 cases of PID would develop, costing $2.2 million in future medical costs. Use
      of EIA to detect chlamydial infection would prevent 240 cases of PID and save
      $887,000 over no screening. Alternatively, use of DNA amplification assays on
      urine specimens would prevent up to an additional 66 cases and save $287,100 over
      EIA. Use of LCR on cervical specimens would prevent at least 13 additional cases
      of PID over the urine-based assays, but would cost $3,005 for each additional
      case prevented. In women receiving routine pelvic examinations, LCR of cervical
      specimens would prevent the most disease and provide the highest cost savings. In
      women not receiving routine pelvic examinations, use of LCR on cervical specimens
      would prevent the most disease but would cost approximately $28,000 per
      additional case of PID prevented over DNA amplification of urine. CONCLUSIONS:
      Compared with EIA screening, the strategy with the lowest program costs, a
      screening strategy that combines use of DNA amplification on cervical specimens
      in women receiving pelvic examinations, and DNA amplification of urine in women
      with no medical indications necessitating a pelvic examination, prevents the most
      cases of PID and provides the highest cost savings. With enhanced sensitivity
      over the other diagnostic assays and with the use of noninvasive specimen
      collection, DNA amplification assays should be implemented as cost-effective
      components of a screening program for C. trachomatis.

PMID- 9518380
TI  - Raising the consciousness for identifying and controlling viral STDs: fears and
      frustrations--Thomas Parran Award Lecture.

PMID- 9518381
TI  - The relationship of cocaine use and human immunodeficiency virus serostatus to
      incident sexually transmitted diseases among women.
AB  - BACKGROUND AND OBJECTIVES: To assess the incidence of sexually transmitted
      diseases (STD) in a group of heterosexual women as a function of human
      immunodeficiency virus (HIV) serostatus and to ascertain the effect of crack
      cocaine use on these relationships. STUDY DESIGN: At baseline, 445 HIV type 1
      (HIV-1) seronegative and 232 seropositive women were provided interviews
      ascertaining demographic and behavioral risk factors. All participants were
      tested for Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas
      vaginalis at baseline and at 6-month intervals. RESULTS: HIV serostatus was not
      related to STD incidence. Although HIV-positive women reported more condom use
      than did HIV-negative women (P < .01), only 65% reported using them consistently.
      Increases in the frequency of crack cocaine use, measured on a 4-point scale,
      were positively associated with rates of new STDs (relative risk [RR] = 1.23, P <
      .01). Crack cocaine use was also associated with greater numbers of sexual
      partners and less consistent condom use. The relationship between HIV status and
      the probability of acquiring an STD was not influenced by frequency of crack use.
      CONCLUSION: Women infected with HIV or who use crack cocaine are at risk for
      transmitting HIV and acquiring other STDs. Whether women are infected with or at
      risk for HIV, programs are needed to prevent and treat crack addiction.
      Interventions should target high-risk sexual practices among both female crack
      users and women living with HIV.

PMID- 9518382
TI  - Attitudes about human immunodeficiency virus immunization: the influence of
      health beliefs and vaccine characteristics.
AB  - BACKGROUND AND OBJECTIVES: The development of a vaccine to prevent human
      immunodeficiency virus (HIV) infection is a highly desirable goal. However, there
      may be a number of psychosocial barriers to HIV vaccine acceptance. The purpose
      of this study was to begin to examine some factors that might influence attitudes
      about HIV immunization. GOAL: To evaluate the relationship of health beliefs and
      vaccine characteristics to acceptability of hypothetical HIV immunization. STUDY
      DESIGN: The subjects were 222 college students who completed self-administered
      questionnaires that addressed health beliefs, vaccine characteristics, and
      acceptability of hypothetical HIV vaccines. RESULTS: Health beliefs independently
      predictive of HIV vaccine acceptability included perceived susceptibility to HIV,
      perceived nonmembership in a traditionally defined acquired immune deficiency
      syndrome (AIDS) risk group, and fear of the vaccine causing AIDS. Of the vaccine
      characteristics, efficacy influenced vaccine acceptability most strongly,
      followed by type of vaccine. CONCLUSION: These results suggest that universal HIV
      vaccine acceptance cannot be assumed and that vaccine characteristics and
      individuals' health beliefs are likely to influence decisions regarding HIV
      immunization.

PMID- 9518383
TI  - Sexually transmitted infections in female sex workers: reduced by condom use but
      not by a limited periodic examination program.
AB  - BACKGROUND AND OBJECTIVES: The sexually transmitted diseases (STD) control
      program for female sex workers (FSW) in Lima, Peru, provided periodic serological
      tests for syphilis and cervical smears for gonococci, but not medication for STD
      or condoms. GOAL OF THIS STUDY: To assess program effectiveness. STUDY DESIGN: We
      assessed prevalence of current STD and serum antibody to STD pathogens in FSW in
      relation to program participation and to condom use. RESULTS: Program
      participation was not associated with significantly reduced rates of current
      gonococcal or chlamydial infections or Venereal Disease Research Laboratory
      (VDRL) titers > or =4 with reactive fluorescent treponemal antibody absorption
      (FTA-ABS). However, regardless of control program participation, consistent
      condom use was associated with reduced prevalence of gonorrhea, and with
      significantly reduced seroreactivity for FTA-ABS, C. trachomatis, anti-hepatitis
      B core (HBc), and anti-human T-lymphotropic virus type I. Anti-HBc was associated
      with years of receiving penicillin injections for syphilis prophylaxis.
      CONCLUSION: The scope, quality, and efficacy of STD control programs must be
      technically appropriate, well managed, and adequately financed. The safety of
      marginal programs warrants scrutiny.

PMID- 9518385
TI  - [A morphometric study of the silver-stained nucleoli in mononuclear and binuclear
      rat hepatocytes].
AB  - Investigation of silver-stained nucleoli has been made in mono- and binuclear rat
      hepatocytes of different ploidy. Morphometric parameters of nucleoli and cell
      ploidy (after silver removing and Feulgen staining) were measured by image
      analyzer "Videotest". It has been shown that the total area and total volume of
      nucleoli correlate with cell ploidy, but the found dependence deviates from the
      proportional one. Possible reasons of such a deviation have been discussed.
      Marked correlation of total area or total volume of nucleoli was detected between
      pairs of nuclei of binuclear hepatocytes, whereas between accidental pairs of
      mononuclear hepatocytes such correlation is practically lacking.

PMID- 9518384
TI  - Interrelationships among douching practices, risky sexual practices, and history
      of self-reported sexually transmitted diseases in an urban population.
AB  - GOALS: To describe the interrelationships of douching, sex during menses, dry
      sex, and anal intercourse and their associations with self-reported history of
      sexually transmitted diseases (STD). STUDY DESIGN: The authors interviewed by
      telephone 422 white Americans (WA) and 44 African Americans (AA) selected using
      random-digit dialing, and 135 AA selected from a listed sample of census tracks
      having a population of at least 40% AA. RESULTS: After adjusting for lifetime
      numbers of vaginal sex partners, sex during menses was associated with self
      reported history of chlamydial infection among women (WA: odds ratio [OR] = 3.9;
      confidence interval [CI]: 1.1, 14.0; AA: OR = 1.6; CI: 0.6, 4.2). Anal sex was
      associated with self-reported history of genital warts, genital herpes,
      hepatitis, and gonorrhea; douching with a twofold increase in self-reported
      pelvic inflammatory disease. Anal sex was most common in women with a history of
      same- and opposite-sex partners. CONCLUSIONS: These data confirm the association
      of douching and anal sex with various STD and suggest that sex during menses is
      associated with chlamydial infection.

PMID- 9518386
TI  - [The developmental characteristics of the embryonic anlagen of rat neocortex and
      spinal cord when transplanted into the distal end of the dissected sciatic nerve
      of adult animals].
AB  - The spinal cord and cerebral cortex of 14 day old embryos of Wistar rats were
      transplanted into the distal stump of the adult rat cut sciatic nerve in order to
      study dynamics of the development of the transplanted cell elements, and to
      elucidate relations of neuronal elements in the central and peripheral nervous
      systems. By means of light and electron microscopy it has been stated that the
      transplanted nerve cells of the cortex and spinal cord could survive for 60 days
      and differentiate from neuroepithelial cells and neuroblasts up to young and
      mature neurons. In the transplants a neuropil is seen to form with both
      unmyelinated and myelinated axons and synaptic contacts. In the cortex
      transplants cavities appear paved with ependyma-like cells having cilia and
      microvilli. It has been found that axons of the transplanted spinal cord neurons
      may leave transplants to be myelinated by the recipient's Schwann cells of the
      peripheral nerve.

PMID- 9518388
TI  - [Nicotinamide decreases DNA destabilization in K562 cells treated with AlF(-4)].
AB  - Using trypan blue exclusion test it has been shown that a 18 hour incubation of
      human erythromyeloleukosis cell line K562 together with AlF(-4) (10 mM NaF + 20
      mkM AlCl3) reduced cell proliferation and survival. However, the latter parameter
      did not change during 4 hours of incubation. Nevertheless, AlF(-4) increased
      fragmentation of 3H-thymidine-labelled DNA by 2-4 times. This effect may be
      suppressed by cultivation of cells with 20 mkM nicotinamide (inhibitor of
      poly(ADP-ribose)polymerase enzyme). We found that incubation of K562 and YAC-1
      cells with 10 mM nicotinamide for 24 hours much reduced their susceptibility to
      non-MHC-restricted lysis by rat spleen cells. This effect may be induced by a
      share of intracellular NAD+ and NADH from destroyed K562 cells; their
      concentration in cells increased under the influence of nicotinamide by 3 times,
      but this effect should be the least because in these conditions nicotinamide does
      not influence the survival of K562 cells. The effect of nicotinamide in both
      cases may be explained by suppression of poly(ADP-ribose)polymerase activity and,
      thus, the rate of DNA reparation. Analysis of AlF(-4) and nicotinamide effects on
      the K562 cells enables us to suppose that suppression of the K562 proliferation
      by tetrafluoroaluminate results in accumulation of reversed damages of DNA.

PMID- 9518387
TI  - [The isolation and analysis of lymphoblastoid cell lines from patients with
      xeroderma pigmentosum and progeria].
AB  - Lymphoblastoid cell lines from patients with xeroderma pigmentosum (2 forms) and
      progeria (unusual form) were established using transformation of peripheral blood
      lymphocytes by Epstein--Barr virus. The influence of different UV doses on cell
      vitality, proliferation and cell cycle progression was studied by means of flow
      cytometry. The cell vitality was determined after incubation of cells with
      etidium bromide and FDA. We used cytograms with two logarithmic signals (log
      green/log red) to discriminate the cell cycle status. Cell cultures were used
      with density of 500,000 cells per 1 ml, previously synchronized at G-phase by the
      incubation in a medium with low serum content. The effect of UV irradiation was
      followed during 72 h. Among four analysed cell lines only line XP2SP demonstrated
      enhanced UV sensitivity, expressed by decreasing of the amount of living cells
      after the UV dose of 2.5 J/m2 and higher. The cell cycle studies showed that
      cells were blocked in S-phase and simultaneously the amount of apoptotic cells
      with both reduced DNA content and ability to bind FDA was seen increased. Similar
      events were observed in the control line only after the dose of 20 J/m2 and
      higher.

PMID- 9518389
TI  - [A comparative analysis of the intracellular potassium content for the
      cardiomyocyte in papillary muscle tissue and in a primary heart culture].
AB  - This work was aimed to examine potassium contents in heart myocytes. The
      intracellular concentration of this element was measured with electron probe
      microanalysis (EPMA). The cardiomyocyte was studied in samples of the papillary
      muscle tissue and in heart primary culture. The low temperature fixation was
      applied to the sample preparation. As a result, cells of the primary heart
      culture were shown to be separated into three kinds of myocytes, defined by their
      different shape, size and cellular potassium content. The rod cardial cell, to be
      used for electrophysiological assays, has potassium and sodium concentrations
      close to those of the papillary muscle. The difference in potassium
      concentrations is to be explained presumably by the injury of cell membrane
      during the primary culture preparation. Healing over the membrane is likely to
      parallel with the membrane damage resulting from a continuous destruction of the
      cellular assembly in primary culture.

PMID- 9518390
TI  - [The characteristics of protein p66--a substrate of the epidermal growth factor
      receptor].
AB  - The p66-kDa protein--a substrate of EGF receptor, is characterized. It is shown
      that the molecule of p66 is recognized by antibodies to phospholipase C gamma 1,
      includes conservative SH2--SH3 domains and lacks N-terminal part of PLC gamma 1.
      Protein p66 is associated to the EGF-R molecule on 992 tyrosine. Protein p66
      binds to both membrane and internalized EGF-Rs and is redistributed with the
      receptors during receptor-mediated endocytosis. It is supposed that p66 may play
      a regulatory role in signal transduction.

PMID- 9518391
TI  - [The possibility of performing artificial selection in vivo for a change in the
      mutability level in populations of mouse bone marrow stem cells].
AB  - Bone marrow cells of CBA males were transplanted to irradiated syngeneic females
      and after 13 days the mean frequency of blood erythrocytes with micronuclei,
      cloning efficiency of haemopoietic stem cells (HSC), and variability range of
      frequency of cells with micronuclei in spleen colonies were studied in 44 primary
      recipients. A wide range of variability has been shown for the indicators of
      mutability and cloning efficiency (0.1-1.8% for frequency of erythrocytes with
      micronuclei, 200-300-1500 for cloning efficiency, 0.1-0.5% for frequency of cells
      with micronuclei in spleen colonies of individual transplants). A weak negative
      correlation between the frequency of erythrocytes with micronuclei and the
      cloning efficiency was observed. We conclude that the difference in frequency of
      erythrocytes with micronuclei between HSC subpopulations is sufficiently high to
      carry out an artificial selection for high and low mutability in the course of
      transplantations. The cloning efficiency can be increased when spleen colonies
      are studied by micronuclear analysis. Data on the importance of such a selection
      in studying the behavior of "mutability" and "cloning efficiency" characters,
      immortalization, "aging", and death of HSC populations of CBA mice have been
      reported.

PMID- 9518392
TI  - [The effect of nocodazole on the redistribution of phosphoinositide-specific
      phospholipase C gamma 1 during mitogenic signal transduction in A-431 cells].
AB  - Phosphoinositide-specific phospholipase C gamma 1 is associated with EGF receptor
      in A-431 cells after EGF treatment. It is shown that phospholipase C gamma 1 is
      co-localized with internalized receptors as well as with membrane ones during
      receptor-mediated endocytosis. Nocodazole is known as an inhibitor of microtubule
      assembly, thus leading to a complete disappearance of microtubule network.
      Nocodazole had no effect on phospholipase C gamma 1--EGF receptor association and
      co-localization, but the intracellular distribution of both the proteins differed
      dramatically. Phospholipase C gamma 1 and EGF receptor were localized in
      endosomes in the periphery of the cell. Besides, pretreatment of A-431 cells with
      nocodazole resulted in decreasing tyrosine phosphorylation of some proteins.
      These data suggest that the internalized receptor may serve as an additional
      starting point for triggering cell signalling.

PMID- 9518393
TI  - Re: Misrepresentation of publications by applicants for radiology fellowships: is
      it a problem?

PMID- 9518394
TI  - 7th Annual Spring Clinical Nephrology Meetings. March 26-29, 1998. Abstracts.

PMID- 9518395
TI  - Effect of intensive therapy on residual beta-cell function in patients with type
      1 diabetes in the diabetes control and complications trial. A randomized,
      controlled trial. The Diabetes Control and Complications Trial Research Group.
AB  - BACKGROUND: Although insulin secretion is severely decreased in most patients
      with type 1 diabetes, levels of residual insulin secretion often vary early in
      the disease. The significance of residual insulin secretion with regard to
      metabolic control and to long-term complications and ways to preserve such
      secretion are not well understood. OBJECTIVE: To compare the effects of intensive
      and conventional therapy on residual insulin secretion in Diabetes Control and
      Complications Trial (DCCT) participants. DESIGN: Multicenter, randomized,
      controlled clinical trial. SETTING: 29 DCCT clinical centers. PATIENTS: 855 of
      the 1441 DCCT participants had had type 1 diabetes for 1 to 5 years at baseline.
      Of these 855 patients, 303 were C-peptide responders (C-peptide level, 0.20 to
      0.50 pmol/mL after ingestion of a standardized, mixed meal); 138 of these
      patients were randomly assigned to intensive therapy, and 165 were assigned to
      conventional therapy. Five hundred fifty-two patients were nonresponders
      (stimulated C-peptide level < 0.2 pmol/mL); 274 of these patients were assigned
      to intensive therapy, and 278 were assigned to conventional therapy.
      INTERVENTIONS: 1) Intensive therapy with 3 or more insulin injections daily or
      continuous subcutaneous infusion of insulin, guided by 4 or more glucose tests
      per day or 2) conventional therapy with 1 or 2 insulin injections daily.
      MEASUREMENTS: Stimulated C-peptide level was measured annually in responders.
      Development of retinopathy and microalbuminuria was assessed annually, hemoglobin
      A1c levels were measured quarterly, and episodes of hypoglycemia were ascertained
      quarterly. RESULTS: Responders receiving intensive therapy maintained a higher
      stimulated C-peptide level and a lower likelihood of becoming nonresponders than
      did responders receiving conventional therapy (risk reduction, 57% [95% CI, 39%
      to 71%]; P < 0.001). As in the entire DCCT cohort, intensively treated responders
      had a reduced risk for retinopathy progression and development of
      microalbuminuria and a higher risk for severe hypoglycemia compared with
      conventionally treated responders. Among intensively treated patients, responders
      had a lower hemoglobin A1c value (P < 0.01), a 50% (95% CI, 12% to 72%) reduced
      risk for retinopathy progression, and a lower risk for severe hypoglycemia (risk
      reduction, 65% [CI, 53% to 74%]; P < 0.001) compared with nonresponders.
      CONCLUSIONS: Intensive therapy for type 1 diabetes helps sustain endogenous
      insulin secretion, which, in turn, is associated with better metabolic control
      and lower risk for hypoglycemia and chronic complications. These observations
      underscore the importance of initiating intensive diabetic management as early as
      safely possible after type 1 diabetes is diagnosed.

PMID- 9518396
TI  - Metabolic risk factors worsen continuously across the spectrum of nondiabetic
      glucose tolerance. The Framingham Offspring Study.
AB  - BACKGROUND: Categorical definitions for glucose intolerance imply that risk
      thresholds exist, but metabolic risk for type 2 diabetes mellitus or
      cardiovascular disease may increase continuously as glucose intolerance
      increases. OBJECTIVE: To examine the distributions of the following metabolic
      risk factors across the spectrum of glucose tolerance: overall and central
      obesity, hypertension, low levels of high-density lipoprotein cholesterol, and
      increased triglyceride and insulin levels. DESIGN: Cross-sectional analysis.
      SETTING: The community-based Framingham Offspring Study. PARTICIPANTS: 2583
      adults without previously diagnosed diabetes. MEASUREMENTS: Clinical data;
      fasting glucose, insulin, and lipid levels; and glucose and insulin levels taken
      2 hours after oral challenge were collected from 1991 to 1993. Glucose tolerance
      was determined by 1980 World Health Organization criteria. Patients with normal
      glucose tolerance were categorized into quintiles of fasting glucose. The
      distributions of each metabolic risk factor and the metabolic sum of the six risk
      factors were assessed across seven categories from the lowest quintile of normal
      fasting glucose level through impaired glucose tolerance and previously
      undiagnosed diabetes. RESULTS: The mean age of patients was 54 years (range, 26
      to 82 years); 52.7% of patients were women. Glucose tolerance testing found that
      12.7% of patients had impaired glucose tolerance and 4.8% had previously
      undiagnosed diabetes. Multivariable-adjusted mean measures of risk factors and
      odds ratios for obesity, elevated waist-to-hip ratio, hypertension, low levels of
      high-density lipoprotein cholesterol, elevated triglyceride levels, and
      hyperinsulinemia showed continuous increases across the spectrum of nondiabetic
      glucose tolerance. Although a threshold effect near the upper range of
      nondiabetic glucose tolerance could not be ruled out for triglyceride levels in
      men and for insulin levels 2 hours after oral challenge in men and women, no
      other metabolic risk factors showed clear evidence of thresholds for increased
      risk. CONCLUSIONS: Metabolic risk factors for type 2 diabetes mellitus and for
      cardiovascular disease worsen continuously across the spectrum of glucose
      tolerance categories, beginning in the lowest quintiles of normal fasting glucose
      level.

PMID- 9518397
TI  - Beverage use and risk for kidney stones in women.
AB  - BACKGROUND: An increase in fluid intake is routinely recommended for patients who
      have had kidney stones to decrease the likelihood of recurrence. However, data on
      the effect of particular beverages on stone formation in women are limited.
      OBJECTIVE: To examine the association between the intake of 17 beverages and risk
      for kidney stones in women. DESIGN: Prospective cohort study with 8 years of
      follow-up. SETTING: United States. PARTICIPANTS: 81093 women in the Nurses'
      Health Study who were 40 to 65 years of age in 1986 and had no history of kidney
      stones. MEASUREMENTS: Beverage use and diet were assessed in 1986 and 1990 with a
      validated, self-administered food-frequency questionnaire. The main outcome
      measure was incident symptomatic kidney stones. RESULTS: During 553 081 person
      years of follow-up over an 8-year period, 719 cases of kidney stones were
      documented. After risk factors other than fluid intake were controlled for, the
      relative risk for stone formation for women in the highest quintile of total
      fluid intake compared with women in the lowest quintile was 0.62 (95% CI, 0.48 to
      0.80). Inclusion of consumption of specific beverages in the multivariate model
      significantly added to prediction of risk for kidney stones (P < 0.001). In a
      multivariate model that adjusted simultaneously for the 17 beverages and other
      possible risk factors, risk for stone formation decreased by the following amount
      for each 240-mL (8-oz) serving consumed daily: 10% (CI, 5% to 15%) for
      caffeinated coffee, 9% (CI, 2% to 15%) for decaffeinated coffee, 8% (CI, 1% to
      15%) for tea, and 59% (CI, 32% to 75%) for wine. In contrast, a 44% (CI, 9% to
      92%) increase in risk was seen for each 240-mL serving of grapefruit juice
      consumed daily. CONCLUSIONS: An increase in total fluid intake can reduce risk
      for kidney stones, and the choice of beverage may be meaningful.

PMID- 9518398
TI  - Thrombotic thrombocytopenic purpura associated with ticlopidine. A review of 60
      cases.
AB  - BACKGROUND: Thrombotic thrombocytopenic purpura, a life-threatening multisystem
      disease, has been infrequently associated with use of ticlopidine, a platelet
      anti-aggregating agent. PURPOSE: To review 60 cases of ticlopidine-associated
      thrombotic thrombocytopenic purpura. DATA SOURCES: Medical records, published
      case reports, and case reports submitted to the U.S. Food and Drug
      Administration. STUDY SELECTION: Instances of ticlopidine-associated thrombotic
      thrombocytopenic purpura were identified. DATA SYNTHESIS: Ticlopidine had been
      prescribed for less than 1 month in 80% of the patients, and normal platelet
      counts had been found within 2 weeks of the onset of thrombotic thrombocytopenic
      purpura in most patients. Mortality rates were higher among patients who were not
      treated with plasmapheresis than among those who underwent plasmapheresis (50%
      compared with 24%; P < 0.05). CONCLUSIONS: Ticlopidine use may be associated with
      the development of thrombotic thrombocytopenic purpura, usually within 1 month of
      initiation of therapy. The onset of ticlopidine-associated thrombotic
      thrombocytopenic purpura is difficult to predict, despite close monitoring of
      platelet counts.

PMID- 9518399
TI  - Update in hematology.

PMID- 9518400
TI  - The debate over physician-assisted suicide: empirical data and convergent views.

PMID- 9518401
TI  - Voluntary death: a comparison of terminal dehydration and physician-assisted
      suicide.

PMID- 9518402
TI  - Remembering the real questions.

PMID- 9518403
TI  - Care of the dying: clinical and financial lessons from the Oregon experience.

PMID- 9518404
TI  - Doctors and ethics, morals and manuals.

PMID- 9518405
TI  - Medicine and commerce. 2: the gift.

PMID- 9518406
TI  - Ethics manual. Fourth edition. American College of Physicians.

PMID- 9518407
TI  - The genie in the bottle.

PMID- 9518409
TI  - Patient care after percutaneous coronary artery interventions.

PMID- 9518408
TI  - Patient care after percutaneous coronary artery interventions.

PMID- 9518410
TI  - Patient care after percutaneous coronary artery interventions.

PMID- 9518411
TI  - Patient care after percutaneous coronary artery interventions.

PMID- 9518412
TI  - Catheter-related bacteremia in patients undergoing hemodialysis.

PMID- 9518413
TI  - Ultrasonographic screening for deep venous thrombosis after arthroplasty.

PMID- 9518414
TI  - Ultrasonographic screening for deep venous thrombosis after arthroplasty.

PMID- 9518415
TI  - Positive-pressure ventilation in amyotrophic lateral sclerosis.

PMID- 9518416
TI  - Hepatitis C virus genotype distribution in B-cell non-Hodgkin lymphoma.

PMID- 9518417
TI  - Anemia secondary to vitamin D intoxication.

PMID- 9518418
TI  - The toxic shock syndrome and Staphylococcus lugdunensis bacteremia.

PMID- 9518420
TI  - AL amyloidosis combined with acquired factor V deficiency.

PMID- 9518419
TI  - Clarithromycin and digoxin toxicity.

PMID- 9518421
TI  - Cardiac rupture during dobutamine stress test.

PMID- 9518423
TI  - Encouraging physical activity.

PMID- 9518422
TI  - Encouraging physical activity.

PMID- 9518424
TI  - What's wrong with this medical student today? Dysfluency on inpatient rounds.

PMID- 9518425
TI  - [Glycopeptide antibiotics resistance mechanism as the basis for novel derivatives
      development capable to overcome resistance].
AB  - The data on the genetic and biochemical bases of bacterial resistance to
      antibiotics of the vancomycin-ristocetin group are summarized. Special emphasis
      is placed on the mechanism of resistance associated with target modification and
      on molecular interactions occurring upon contact of glycopeptides with normal and
      modified targets. The prospects for developing new derivatives active against
      resistant bacteria are discussed. The most rational approach to the chemical
      transformation of glycopeptides involves the modification of the internal
      "binding pocket" and the peripheral regions of the molecule that participate in
      the stabilization of the antibiotic-target complex. Novel semisynthetic drugs of
      this group active against glycopeptide-resistant enterococci are described.

PMID- 9518427
TI  - [Detection of nucleic amino acid enantiomers by HPLC with preliminary
      modification by o-phthalic aldehyde].
AB  - The use of reversed-phase HPLC with UV detection at 254 nm for the separation of
      stereoisomers of nucleoamino acids, namely, pyrimidyl and purinyl derivatives of
      alanine, after premodification with o-phthalic aldehyde and N-acetyl-L-cysteine
      was studied. The use of 0.01 M phosphate buffer (pH 7.0) containing 5%
      acetonitrile as a mobile phase resulted in satisfactory separation. The range of
      the detectable amounts of nucleoamino acids was 0.08-1.0 nmol. This method was
      used for monitoring the formation of stereoisomers in the hydrolysis of N
      phenylacetylcytosinylalanine.

PMID- 9518426
TI  - [Affinity sorbents with tripeptide morpholine ligands for isolation of
      proteases].
AB  - New affine sorbents were synthesized involving tripeptide morpholides H-Ala-Ala
      Leu-Mrp and H-D-Ala-Leu-Arg-Mrp as ligands that mimic substrates of subtilisin
      like proteases and kallikrein, respectively. These were used for the isolation
      and purification of several proteases: trypsin, pepsin, alpha-chymotrypsin,
      thrombin, kallikrein, and termitase and were also efficient in the isolation of
      proteolytic enzymes from complex mixtures, such as the urine of children
      suffering from glomerulonephritis, hepatopancreas of Kamchatka crab, and
      dandelion roots. The ligands are competitive inhibitors of a number of proteases,
      and therefore, they were supposed to interact with the substrate binding sites in
      these enzymes.

PMID- 9518428
TI  - [In vitro cloning of DNA fragments by one polymerase chain reaction].
AB  - An improved version of the in vitro DNA cloning method described earlier is
      proposed. The method allows amplification by polymerase chain reaction (PCR) of
      individual DNA molecules of an unknown primary structure followed by sequencing.
      The modifications described here provide for in vitro cloning by means of a 40-45
      cycle PCR (the original protocol required two consecutive amplifications). In
      addition, the in vitro cloning is suggested to be carried out in special 96-well
      plates in the presence of ethidium bromide; upon UV irradiation, the wells
      containing amplified DNA fluoresce to make the analysis of all 96 wells
      unnecessary. The improved protocol makes the preparation of individual in vitro
      clones more straightforward and less expensive.

PMID- 9518429
TI  - [Relation between the level of E. coli gene expression and the structure of
      translation initiation region (TIR). III. Sites of complementary interaction of
      TIR with 16S rRNA].
AB  - Potential sites of the complementary interaction of the translation initiation
      region (TIR) with 16S rRNA are revealed, and the role of these sites in the gene
      expression level is studied. The high expression level of a gene depends not only
      on the complementary interaction of TIR with 16S rRNA in sites proximal to the
      start codon [anti-Shine-Dalgarno (ASD) (delta G > -8 to -10 kcal/mol) and
      downstream box (DB)] and located at the -15 to +20 mRNA region but also on
      complementary interactions in distal sites of the untranslated branch of TIR
      (mTIR). Among them, the UB (upsteam box) 1 site, complementarily interacting with
      the exposed 452-490 segment of the 440-490 loop of 16S rRNA, may be located in
      the -15 to -50 mTIR segment. In the -50 to -70 mTIR segment may be located UB2
      and UB3 sites, which interact with the exposed segment 478-488 of the 440-490
      loop and segment 520-532 of the 520-540 loop of 16S rRNA, the UB3 site being much
      more efficacious. The high expression level requires that the total free energy
      of complementary interactions of UB1, UB2, and UB3 sites with 16S rRNA exceeds 
      20 kcal/mol.

PMID- 9518430
TI  - [Interaction of short nucleotide derivatives with nucleic acids. IV. Modification
      of DNA by an alkylating tetranucleotide reagents in the presence of effectors in
      perfect and imperfect complexes].
AB  - It was demonstrated that any mismatches in a complex formed by an ssDNA target
      and a tetranucleotide at 25 or 37 degrees C can be discriminated by alkylating
      the DNA with a tetranucleotide carrying a 4-[N-methyl-N-(2
      chloroethyl)]aminobenzylethylamine residue at the 5'-terminal phosphate in the
      presence of a pair of flanking effectors, octanucleotide di-N-(2-hydroxyethyl)
      phenazinium derivatives. The discrimination factor (ratio of the extent of the
      target modification in the perfect and mismatch-containing complexes) for a
      single mismatch in the tetranucleotide binding site at 25 degrees C varied
      between 4 and 500 depending on the type of mismatch and its location in the
      complex and exceeded 400 at 37 degrees C for all the investigated mismatches. The
      DNA target modification by the alkylating derivative of the 3'-estrone ester of
      tetranucleotide pCAGX (mean = C, T, A or G) was selective in the presence of a
      pair of hydrophobic effectors, octanucleotide 5'-cholesteryl-3'-phenazinium
      derivatives. The discrimination factors for 3'-terminal mismatches T.G, A.G, and
      G.G were 1,8,400, and 400, respectively.

PMID- 9518431
TI  - [Synthesis and antiherpes activity of acyclovir phosphoesters].
AB  - 9-(Hydroxyethyloxymethyl)guanine (acyclovir) phosphite and fluorophosphate were
      synthesized by the reactions of acyclovir with phosphorus trichloride in triethyl
      phosphate and with fluorophosphoric acid in the presence of 2,4,6
      triisopropylbenzenesulfonyl chloride, respectively, and characterized by the data
      of 1H and 31P NMR and mass spectra. These products selectively inhibit
      reproduction of the herpes simplex virus type 1 in the Vero cell culture, the
      phosphite being also substantially active against a herpes virus strain resistant
      to acyclovir.

PMID- 9518432
TI  - [Study of sialated neoglycoconjugates by surface enhanced Raman scattering
      spectroscopy].
AB  - Neoglycoconjugates based on polyacrylamide and sialic acid with N
      acetylneuraminic acid or sialooligosaccharides as side chains were studied by
      surface-enhanced Raman scattering (SERS) spectroscopy. It had previously been
      found that these polymers can effectively inhibit influenza virus adhesion. This
      study revealed the possibility to evaluate, based on the intensity of SERS
      signals, the overall availability for interaction and the conformational freedom
      of sialic acid residues in glycoconjugates. The dependence of these two factors
      on the structure and density of sialylated side chains was studied. The
      uniformity of distribution of sialylated side chains in conjugates was shown.
      Comparison of the results of the SERS spectroscopic study of the conjugates and
      the data on their inhibitory effect on the adhesion of specific strains of
      influenza virus allowed the identification of the conjugates for which the
      availability and conformational freedom of sialic acid are the main factors
      determining their inhibitory properties. A conclusion was also reached about the
      predominance of one of the mechanisms (competitive inhibition or steric
      stabilization) in the inhibitory properties of the specific conjugates.

PMID- 9518433
TI  - Health effects of indoor fluoride pollution from coal burning in China.
AB  - The combustion of high fluoride-content coal as an energy resource for heating,
      cooking, and food drying is a major exhaust emission source of suspended
      particulate matter and fluoride. High concentrations of these pollutants have
      been observed in indoor air of coal-burning families in some rural areas in
      China. Because airborne fluoride has serious toxicological properties, fluoride
      pollution in indoor air and the prevalence of fluorosis have been analyzed in a
      fluorosis area and a healthy nonfluorosis area in China and in a rural area in
      Japan. For human health, fluoride in indoor air has not only been directly
      inhaled by residents but also has been absorbed in stored food such as corn,
      chilies, and potatoes. In the fluorosis area in China, concentrations of urinary
      fluoride in the residents have been much higher than in the nonfluorosis area in
      China and in the rural area in Japan. In the fluorosis area, almost all
      elementary and junior high school students 10-15 years of age had dental
      fluorosis. Osteosclerosis in the skeletal fluorosis patients was very serious.
      Urinary deoxypyridinoline in rural residents in China was much higher than in
      rural residents in Japan. Data suggest that bone resorption was extremely
      stimulated in the residents in China and that fluoride may stimulate both bone
      resorption and bone formation. Because indoor fluoride from combustion of coal is
      easily absorbed in stored food and because food consumption is a main source of
      fluoride exposure, it is necessary to reduce airborne fluoride and food
      contamination to prevent serious fluorosis in China.

PMID- 9518434
TI  - Otolaryngology in the information age: enabling technologies for the future of
      surgery. Enabling technologies for the future of surgery.
AB  - Enabling technologies for the future, whether exemplified by endoscopic,
      minimally invasive, or microdexterity systems or surgical and nonsurgical image
      guided procedures, continue with an evolution so rapid that before one change has
      been accepted and perfected, another even more dramatic change promises to
      replace it. These information-based surgical and procedural interventions are
      just now becoming accepted standards of surgical, radiologic, and medical
      practice, and yet the promise of more advanced technologies blurs even these new
      boundaries, constantly redefining the concept of "surgery." It is essential that
      otolaryngologists, as part of the broader spectrum of physicians, understand
      these changes and prepare to adapt and improve each and every one of their
      technical and cognitive skills.

PMID- 9518435
TI  - Otolaryngology and the Internet. E-mail and the World Wide Web.
AB  - Computer technology and Internet-based communications are evolving at a
      tremendous rate. At present, most physicians either have or can easily obtain
      online access. E-mail represents a new method of interpersonal communication,
      with many useful applications in the field of clinical medicine. The World Wide
      Web has developed over the past few years into a vast information resource, with
      global reach and the ability to provide users with text and audio and video
      materials on every conceivable topic. These modalities are discussed in detail,
      stressing controversial aspects such as e-mail security, validation of content,
      professional liability as it relates to online comments, and the academic status
      of Web publishing.

PMID- 9518436
TI  - Searching the medical literature.
AB  - The widespread use of computers and the Internet have made searching the medical
      literature easier and more accessible to most physicians. The National Library of
      Medicine (NLM) maintains MEDLINE, a comprehensive, cross-referenced database of
      citations to the medical literature covering 1966 to the present. The NLM
      maintains several other literature databases that are also available online. In
      1996, the NLM began providing free, unlimited access to MEDLINE to all Americans
      over the World Wide Web. This article discusses how to perform effective and
      efficient literature searches using MEDLINE and other databases.

PMID- 9518437
TI  - The computerized patient record.
AB  - Interest in electronic medical records and computerized patient records began
      with a desire to efficiently retrieve data for outcomes research. One of the best
      ways to improve medical care is through good clinical outcomes research, which
      requires accurate, detailed clinical information. In investigating different
      systems for recording and codifying the information, the authors found that no
      real systems existed. The detailed information collected for outcomes research
      could be used for a variety of other processes in the business of health care and
      is thus worthy of being efficiently recorded.

PMID- 9518438
TI  - Computer-based physician education.
AB  - Physicians are turning to computers with increasing frequency to access patients'
      records and laboratory values, to communicate with colleagues, and to keep
      current with the developments in their field. This article reviews the impact of
      the computers on the education of medical students and on continuing education
      for residents and practicing physicians. Furthermore, it emphasizes the
      importance and need for educating physicians about computers and the basic
      principles behind their development.

PMID- 9518439
TI  - Computer-based patient education.
AB  - The computer can be a powerful ally in clinicians efforts to empower their
      patients to make the right individual decisions. The Internet, in particular, is
      an extremely valuable resource that enables patients to quickly obtain the latest
      information on support groups, therapeutic modalities, late-breaking research,
      and individual coping strategies. The technology is now mature enough that every
      provider should consider incorporating some type of computer-based patient
      education into his or her practice.

PMID- 9518440
TI  - Telemedicine in otolaryngology.
AB  - Telemedicine or the electronic transmission of medical data has become an even
      more important part of medical practice with developing technology. How to best
      use this technology to enhance and empower both physician and patient is the
      challenge. What is there, what is coming, and thoughts regarding how
      otolaryngologists may benefit by incorporating "teleotolaryngology" in their
      practice is the thrust of this article.

PMID- 9518441
TI  - Computer-augmented endoscopic sinus surgery.
AB  - Review of current literature on computer-augmented endoscopic sinus surgery
      reflects a sustained interest in developing a role for available frameless
      stereotactic technologies to provide image guidance for the surgeon. The interest
      is motivated by the prospect of increased intraoperative patient safety in that
      image guidance assists the surgeon in navigating through diseased or surgically
      revised complex anatomy. The authors feel that in time the technique will enable
      a new level of efficiency in endoscopic sinus surgery.

PMID- 9518443
TI  - Advanced surgical technologies for plastic and reconstructive surgery.
AB  - Virtual reality creates a simulated world in which the surgeon can practice and
      plan complex surgical procedures. This simulated world can be especially valuable
      in head and neck surgery, including congenital craniofacial surgery, facial
      trauma, and resection and reconstruction of head and neck tumors, whereby the
      complexity of the anatomy and the difficulty of the problems test the surgeon's
      abilities. The author presents a brief history of simulations and surgery, a
      background to plastic surgery simulators, and discuss the problem of limited
      human body models in past systems. Computer-aided surgery and virtual reality
      technologies are also reviewed.

PMID- 9518442
TI  - Using advanced simulation technology for cranial base tumor evaluation.
AB  - Skull base tumors are considered one of the most difficult pathologic entities to
      diagnose and treat. The physician is heavily dependent on imaging studies to
      determine the best form of treatment. As imaging technology becomes more
      advanced, the physician will need to be able to intuitively explore the complex
      data. Such intuitive exploration requires the use of high performance computer
      hardware and software. Issues related to this concept and a summary of current
      work in this area are presented.

PMID- 9518444
TI  - Virtual environments. Surgical simulation in otolaryngology.
AB  - Advanced technology in the form of computer-generated surgical simulation has
      tremendous potential as an adjunctive training aid to residents in training and
      experienced surgeons. This article explores the state-of-the-art in surgical
      simulation for otolaryngologists and future directions in this area.

PMID- 9518445
TI  - Virtual otoscopy.
AB  - Imaging techniques assist the surgeon in diagnosis of disease, surgical planning,
      and providing image guidance during surgery. Endoscopy has the drawback of being
      a minimally invasive procedure and limiting visualization to the inner surface of
      the lumen. Ultrasound, CT, and MR imaging show volumes of tissue beyond the lumen
      wall; however, their planar, two-dimensional representations require mental
      reconstruction of anatomic structures, which often proves difficult with the
      small, complex structures within the temporal bone. To improve three-dimensional
      visualization of the inner ear, we successfully completed a virtual model that
      can be displayed as a contiguous, three-dimensional luminal view, known as
      virtual otoscopy, which emulates traditional endoscopy. A concomitant global view
      and a view of the related CT slice adds a distinct advantage in the presentation
      and study of this complex organ. Advances in computer and software technology may
      overcome the time and cost factors that, at present, limit widespread use of
      virtual otoscopy. Overall, virtual otoscopy stands as a promising new
      visualization technique for elucidation of the middle ear, inner ear, and
      temporal bone structures.

PMID- 9518454
TI  - Expression of human monocyte chemoattractant protein-1 in the yeast Pichia
      pastoris.
AB  - The human monocyte chemoattractant protein-1 (MCP-1) was expressed at high levels
      in Pichia pastoris with the alcohol oxidase promoter. It was secreted from the
      yeast when either its natural signal sequence or the Saccharomyces cerevisiae
      alpha-factor signal peptide was used. SDS-PAGE and Western blot revealed two
      immunoreactive MCP-1 species at 15 and 8.5 kDa designated MCP-1H and MCP-1L,
      respectively; both were purified by cation-exchange chromatography. MCP-1H could
      be converted to MCP-1L by treatment with peptide N-glycosidase F, showing that
      the former is an N-glycosylated form of the latter. Laser desorption mass
      spectrometry showed that MCP-1L actually consisted of a mixture of three
      polypeptides of 8449, 8614, and 8780 Da and MCP-1H showed a broad peak at 11,134
      Da. N-terminal peptide sequencing indicated that nearly half of MCP-1L lacked the
      two N-terminal amino acids found in the native protein. Both MCP-1H and MCP-1L
      could induce monocyte migration and calcium influx in THP-1 monocytic leukemia
      cells, although these activities were about 10- to 100-fold lower than those of
      MCP-1 produced in insect cells.

PMID- 9518455
TI  - Recombinant production of cyanovirin-N, a potent human immunodeficiency virus
      inactivating protein derived from a cultured cyanobacterium.
AB  - Here we describe the recombinant production and purification of a novel anti
      human immunodeficiency virus (HIV) protein, cyanovirin-N (CV-N), in Escherichia
      coli. Initial attempts to express CV-N using a vector containing an ompA signal
      peptide sequence resulted in production of an intractable mixture of the full
      length (101 amino acid residue) protein and a truncated form lacking the first
      two N-terminal amino acids. The truncated protein was observed regardless of the
      host cell line, culture conditions, or induction time. These observations
      suggested that an as yet unidentified protease or peptidase was responsible for
      proteolytic cleavage between the second and third N-terminal amino acids of CV-N
      when presented as an ompA-CV-N fusion protein. When the ompA signal peptide
      sequence was replaced by a pelB signal peptide sequence, CV-N was produced in
      high yield as a single, homogeneous protein. This was confirmed by electrospray
      ionization mass spectrometry and N-terminal sequencing. This expression system
      provides a basis for large-scale production of clinical grade CV-N for further
      research and development as an anti-HIV microbicide.

PMID- 9518457
TI  - Stabilization of recombinant Drosophila acetylcholinesterase.
AB  - The uses of pure and stable acetylcholinesterase can range from simple basic
      research to applications in environment quality assessment. In order to satisfy
      some of these needs its recombinant expression is routinely performed. Affinity
      purified recombinant Drosophila melanogaster acetylcholinesterase proved to be
      instable; an apparent cause of this seemed to be the presence of contaminants
      with protease activity as evidenced by SDS-PAGE. The elimination of these
      accompanying products was achieved by anion-exchange, hydrophobic interaction,
      and cibacron blue affinity chromatography applied downstream from procainamide
      affinity chromatography. The utilization of a parallel affinity acting via an
      engineered histidine tail permitted the elimination of the copurified proteases
      as well. Despite the elimination of the contaminants, the apparently pure
      extracts were still unstable. It is shown that such instability can be
      counterbalanced by provoking protein-protein interactions, either between enzyme
      molecules or with other molecules such as bovine serum albumin. Another way to
      reduce instability is the addition of a reversible inhibitor or polyethylene
      glycol 3350.

PMID- 9518456
TI  - Expression of eukaryotic proteins in soluble form in Escherichia coli.
AB  - At the optimum temperature for its growth (37 degrees C), Escherichia coli tends
      to accumulate heterologous proteins in insoluble form. Fusion protein technology
      has been used to increase the solubility of overexpressed proteins in this
      organism, but with variable degrees of success. Fusion to a mutant form of DsbA
      (DsbAmut) confers higher levels of solubility to heterologous proteins in a
      reproducible way, even when E. coli is grown at 37 degrees C. We have shown this
      to be true with a diverse sample of eukaryotic proteins: IGF-I, IGFBP-3, 3C
      proteinase, TGF beta-2, sTGF beta-RII, BDNF, GDNF, mEGFBP, leptin, and GFP. In
      addition, we have investigated the effects of charge average and proline content
      on the solubility of DsbAmut fusions. Coexpression of a protein prolyl isomerase
      [cyclophilin (L-)] and modification of selected asparagine residues to aspartic
      acid appear to have beneficial effects on the accumulation of soluble
      heterologous proteins.

PMID- 9518458
TI  - Cloning, overexpression, and purification of cytosine deaminase from
      Saccharomyces cerevisiae.
AB  - Cytosine deaminase is an enzyme which has been investigated for cancer
      chemotherapy as a result of its ability to convert the relatively nontoxic
      prodrug 5-fluorocytosine into the anticancer drug 5-fluorouracil. To facilitate
      investigations of the utility of cytosine deaminase for cancer chemotherapy, we
      have cloned and expressed the enzyme from Saccharomyces cerevisiae. The DNA
      sequence translates into a protein of 158 amino acids in length, with a predicted
      molecular weight of 17,563 kilodaltons. Alignment of the cytosine deaminase
      protein sequence from yeast with a variety of proteins defines a novel sequence
      motif of cytosine or cytidine binding enzymes. Recombinant expression cassettes
      encoding cytosine deaminase were transfected into monkey kidney COS cells, which
      lack endogenous cytosine deaminase, to test for production of a functional
      protein. Cell extracts from these transfectants contained detectable levels of
      enzyme activity capable of converting 5-fluorocytosine to 5-fluorouracil.
      Cytosine deaminase was expressed in yeast from a cDNA cassette under the control
      of an inducible promoter, increasing expression 250- to 300-fold relative to wild
      type strains. A purification protocol has been developed which permits recovery
      of 60% of cytosine deaminase in active form from induced cell lysates after two
      purification steps. This protocol will be useful for isolating large quantities
      of pure enzyme which are required for the preclinical evaluation of monoclonal
      antibody-cytosine deaminase conjugates in combination with 5-fluorocytosine.

PMID- 9518459
TI  - Codon optimization of the gene encoding a domain from human type 1 neurofibromin
      protein results in a threefold improvement in expression level in Escherichia
      coli.
AB  - An internal domain from the human type 1 neurofibromin has previously been
      expressed in Escherichia coli as a fusion with gluthathione S-transferase (GST).
      The expression level of this protein was lower than expected and so a gene was
      constructed using the distribution of codons found in highly expressed E. coli
      proteins. Codons were assigned using a Microsoft Visual Basic computer program to
      give a distribution similar to those found in genes which are highly expressed in
      E. coli. The optimized gene was then cloned back into the same GST fusion plasmid
      and it was found that the expression of soluble protein had increased threefold.

PMID- 9518460
TI  - Human keratinocyte growth factor recombinantly expressed in Chinese hamster ovary
      cells: isolation of isoforms and characterization of post-translational
      modifications.
AB  - Keratinocyte growth factor (KGF) is a member of the fibroblast growth factor
      family that acts specifically on epithelial cells in a paracrine mode. We
      employed a mammalian expression system to synthesize recombinant human KGF and
      isolated two preparations, KGF-a and KGF-b, from medium conditioned by Chinese
      hamster ovary cells. On an SDS-PAGE gel, KGF-a migrates as two bands near 25-29
      kDa and contains both N- and O-linked sugar moieties attached near the N
      terminus. Detailed structural characterization confirms that KGF-a contains a
      single amino acid sequence predicted from cDNA sequence and the molecule has two
      intramolecular disulfide bridges, Cys1-Cys15 and Cys102-Cys106. An additional Cys
      at position 40 is free and resides in a solvent-inaccessible environment. Mass
      spectrometric analyses of KGF-a peptides verify the occurrence of several post
      translational modifications in the molecule, including partial oxidation at
      Met28, partial sulfation at Tyr27, and glycosylation at Asn14 and Thr22. The Asn
      linked carbohydrate structures are heterogeneous, which include biantennary,
      triantennary, and tetraantennary structures with none or up to four sialic acids
      attached to various structures, while the Thr-linked carbohydrates contain
      typical mucin-type structures. KGF-b is an N-terminally truncated form of KGF-a
      posttranslationally processed at Arg23 and is not glycosylated. Both KGF-a and
      KGF-b forms are capable of stimulating DNA synthesis in quiescent Balb/MK mouse
      epidermal keratinocytes.

PMID- 9518461
TI  - Expression of recombinant human soluble type II transforming growth factor-beta
      receptor in Pichia pastoris and Escherichia coli: two powerful systems to express
      a potent inhibitor of transforming growth factor-beta.
AB  - Transforming growth factor-beta (TGF-beta) is a potent regulator of cell
      metabolism, proliferation, and differentiation. To study the role of endogenous
      TGF-beta in processes such as tissue repair and inflammation, potent and specific
      inhibitors are required. Because the type II TGF-beta receptor (TGF beta RII) has
      a high affinity for TGF-beta, the extracellular domain of TGF beta RII (TGF-beta
      sRII) was expressed in Pichia pastoris and Escherichia coli. Expression of the
      soluble TGF beta sRII using P. pastoris resulted in a soluble, heterogeneously
      glycosylated protein which was secreted into the medium. Although expression of
      TGF beta sRII in E. coli resulted in the formation of insoluble inclusion bodies,
      solubilization and refolding resulted in a biologically active protein. Because
      in both systems a C-terminal 6x His coding sequence was inserted behind the
      coding sequence for the extracellular domain of TGF beta RII the recombinant
      proteins could be purified by a powerful, single-step procedure using a Ni-NTA
      agarose. The purified proteins appeared to be potent inhibitors of TGF-beta 1 and
      TGF-beta 3. In contrast, TGF beta sRII was less effective in neutralization of
      TGF-beta 2. In conclusion, biologically active TGF beta sRII can be produced
      using P. pastoris and E. coli expression systems. The ease of these expression
      systems, the powerful single step purification and low costs makes it possible to
      produce TGF beta s RII in large amounts to further elucidate the role of TGF-beta
      1 and TGF-beta 3 in physiological processes like tissue repair and inflammation.

PMID- 9518462
TI  - Expression of human interleukin-17 in Pichia pastoris: purification and
      characterization.
AB  - A Pichia pastoris expression clone has been developed to produce the human
      cytokine interleukin-17 (hIL-17). Characterization of purified recombinant hIL-17
      made with this clone demonstrated that it shared many characteristics with hIL-17
      produced in mammalian cells. The hIL-17 produced in Pichia had the correct N
      terminus of natural mature hIL-17 and a glycosylation pattern similar to hIL-17
      produced in mammalian cells; both Pichia and human cells add approximately 5 kDa
      of sugars via N-linked glycosylation and both express a mixture of the
      glycosylated and nonglycosylated forms. Gel filtration provides evidence that the
      Pichia produced hIL-17 exists as a dimer in solution. A combination of cation
      exchange and gel-filtration chromatography yielded 3.5 mg of highly purified and
      biologically active hIL-17 from a 10-liter fermentation. These results show that
      P. pastoris is a useful system to produce recombinant hIL-17 in
      structure/function studies of this molecule.

PMID- 9518463
TI  - Purification and characterization of recombinant forms of TCL-1 and MTCP-1
      proteins.
AB  - The TCL-1 gene which is located on chromosome 14 plays a major role in human
      hematopoeitic malignancies and encodes a 14-kDa protein whose function has not
      been determined. The TCL-1 gene is expressed in pre-B cells, in immature
      thymocytes, and at low levels in activated T cells but not in peripheral mature B
      cells and in normal cells. The TCL-1 protein is similar in its primary structure
      to a protein encoded by the mature T cell proliferation gene (MTCP-1). The MTCP-1
      gene is located on the X chromosome and has been shown to be involved in rare
      chromosomal translocations in T cell proliferative diseases. The TCL-1 and MTCP-1
      genes appear to be members of a family of genes involved in lymphoid
      proliferation and T cell malignancies. Our laboratory has undertaken the study of
      the TCL-1 and MTCP-1 proteins to determine the structure and the function of
      these related proteins. In the present report, we have produced, using a
      bacterial expression system, both purified TCL-1 and MTCP-1 proteins in forms
      with and without a six His tag sequence. The recombinant proteins were purified
      by chromatography on a Ni-NTA resin followed by reverse-phase FPLC using a buffer
      system at pH 7.9 and a polymeric-based reverse-phase column. The MTCP-1
      recombinant proteins display greater solubility, do not form disulfide linked
      dimers or oligomers, and elute at a lower isopropanol concentration than the
      corresponding TCL-1 proteins. The purified recombinant TCL-1 and MTCP-1 proteins
      have been characterized by N-terminal sequence analysis, time of flight mass
      spectrometry, and circular dichroism spectroscopy. Initial results have indicated
      that the MTCP-1 protein with the His tag removed is suitable for both NMR and X
      ray crystallographic methods of structure determination.

PMID- 9518464
TI  - Reverse-phase chromatography isolation and MALDI mass spectrometry of the
      acetylcholine receptor subunits.
AB  - A procedure for purifying the Torpedo californica nicotinic acetylcholine
      receptor subunits is proposed which involves preparative SDS-PAGE followed by
      reverse-phase HPLC on a C4 column in an acetonitrile-isopropanol system. By this
      method, the alpha-subunit can be completely separated from the 43-kDa protein
      which migrates very close to it on SDS-PAGE, and the delta-subunit can be
      isolated free from the beta-subunit of Na+, K(+)-ATPase comigrating with it on
      SDS-PAGE. The purity of all acetylcholine receptor subunits thus obtained was
      verified by Edman degradation and MALDI mass-spectrometric analysis which could
      be performed quite easily on the HPLC-purified samples. In general, we observed a
      good correlation between the experimentally determined molecular masses and those
      calculated from the amino acid sequences and when known, posttranslational
      modifications (glycosylation and phosphorylation) of individual receptor
      subunits. Transfer of the isolated receptor subunits into 1% octyl-beta-D
      glucopyranoside generates samples suitable for functional studies and enzymatic
      proteolysis or deglycosylation.

PMID- 9518465
TI  - Overproduction and purification of glutaryl 7-amino cephalosporanic acid acylase.
AB  - The gene encoding glutaryl 7-amino cephalosporanic acid acylase (GL-7ACA acylase)
      from Pseudomonas sp. 130 has been cloned and expressed in Escherichia coli using
      a high-level expression system. The specific activity of the acylase in the crude
      extract of cells in this system is approximately 10 times that in the previous
      one. The overproduced enzyme can be easily isolated within 3 days to a purity of
      over 90% by a simple and inexpensive two-step preparative chromatographic method
      with an overall yield of nearly 50%. The deletion of the signal peptide and
      mutation in the alpha-subunit of the acylase have little influence on its
      posttranslational processing and its kinetic parameters.

PMID- 9518466
TI  - Expression, purification, and characterization of recombinant human interleukin
      13 from NS-O cells.
AB  - Interleukin-13 is a cytokine which is secreted by activated T lymphocytes and
      primarily impacts monocytes, macrophages, and B cells. A synthetic gene coding
      for human interleukin-13 has been prepared and cloned into expression vector
      pEE12. The construct was transfected into NS-O cells, which showed stable
      expression of the recombinant protein. A four-step purification procedure
      consisting of S-Sepharose, Q-Sepharose, hydroxyapatite, and Sephacryl-100
      chromatographies yielded bioactive interleukin-13 of > 98% purity. The purified
      protein was structurally characterized. The extinction coefficient at 280 nm was
      determined to be 5678 M-1 cm-1. Amino acid sequencing confirmed that the N
      terminus of the purified protein was intact. Electrospray mass spectrometric
      analysis, size-exclusion chromatography, and SDS-PAGE revealed that the
      biologically active protein is monomeric and unglycosylated. Mass spectrometry
      and a chemical assay for free sulfhydryls indicated that the four cysteine
      residues of interleukin-13 are involved in two intramolecular disulfide bonds.
      The circular dichroism spectrum confirms that interleukin-13 belongs to the alpha
      helical family of cytokines. A biologically inactive covalent trimer also forms
      in the cell culture, but can be separated from the monomer by the hydroxyapatite
      and size-exclusion chromatographies. These data indicate that human interleukin
      13 retains many structural similarities to human interleukin-4, from which it
      arose by a gene duplication event.

PMID- 9518467
TI  - Efficient secretion of biologically active recombinant OB protein (leptin) in
      Escherichia coli, purification from the periplasm and characterization.
AB  - The genes encoding the mature forms of mouse (mOB) and human OB (hOB) protein
      (also called leptin) were fused to the secretion signal coding sequence of the
      Escherichia coli outer membrane protein A (sOMP A). The hybrid genes were
      preceded by a ribosome binding site (RBS) and were expressed under
      transcriptional control of both the lipoprotein promoter (Plpp) and the lac
      promoter-operator (POlac). The recombinant fusion proteins were efficiently
      expressed and exported into the periplasmic compartment of E. coli cells from
      where they were recovered by osmotic shock as soluble mature polypeptides with
      the sOMP A precisely removed. Recombinant mOB and hOB proteins were also produced
      in Sf9 insect cells using the baculovirus expression system. Milligram quantities
      of both proteins were purified to homogeneity using ion-exchange, hydrophobic
      interaction chromatography and gel filtration and were found to be biologically
      active and to have antiobesity effects upon testing in genetically obese ob/ob
      mice.

PMID- 9518468
TI  - Mass spectrometric characterization and glycosylation profile of bovine
      pancreatic bile salt-activated lipase.
AB  - We developed a procedure for the large scale isolation of bovine bile salt
      activated lipase (BAL) for its crystallization [Wang, X., et al. (1997) Structure
      5, 1209-1218] and also carried out a study on the molecule's glycosylation
      profile for a better deduction of the structure of the enzyme. Mass spectrometric
      analysis of the CNBr-generated peptides indicated that only one (Asn-361) of the
      two potential N-glycosylation sites (Asn-187 and Asn-361) with NXT motif is
      glycosylated. The analysis of the isolated CNBr peptide containing Asn-361 showed
      that it existed in three glycoforms in a ratio of 1.0:2.8:1.0, with
      oligosaccharide moieties weighing 1900.1, 2045.2, and 2336.4 Da, respectively.
      The major oligosaccharide chain contained mannose: galactose:N
      acetylglucosamine:fucose:sialic acid in a molar ratio of 2:2:4:2:1. It was also
      determined that the potential O-glycosylated peptide (CB13) is not O-glycosylated
      and, in addition, it was found that there was microheterogeneity in the C
      terminus of the isolated bovine BAL. The results obtained from this mass
      spectrometric study combined with the X-ray crystallographic studies provide more
      precise structural information on BAL. The procedure described here for the mass
      spectrometric analysis of CNBr-generated peptides also has general applicability
      for analysis of the glycosylation profile of glycoproteins and the C-terminal
      peptide structure of proteins.

PMID- 9518469
TI  - Human and porcine aminoacylase I overproduced in a baculovirus expression vector
      system: evidence for structural and functional identity with enzymes isolated
      from kidney.
AB  - Aminoacylase I (EC 3.5.1.14) is one of the most abundant enzymes in the cortical
      region of mammalian kidney. Both the porcine and the human enzyme were
      overexpressed using baculovirus expression vector systems and purified by
      hydrophobic interaction chromatography and anion-exchange chromatography. The
      resulting preparations were analyzed for structural and functional identity with
      the corresponding enzymes isolated from kidney. The dansyl method as well as mass
      spectroscopy confirmed N-terminal blocking. For the porcine enzyme, atomic
      absorption spectroscopy yielded the correct metal content (one zinc per subunit).
      Kinetic analyses showed identical Km values for the expression products and the
      enzymes isolated from kidney. By contrast, the porcine enzyme when overexpressed
      in Escherichia coli had a much lower specific activity. Comparative substrate
      specificity studies with natural and recombinant human aminoacylase and 16
      different N-acetyl-L-amino acids showed that, among the derivatives of
      proteinogenic amino acids, N-acetyl-L-methionine was the best substrate, followed
      by acetylated glutamate, leucine, alanine, and valine. These amino acids are also
      the most abundant residues at the N-termini of acetylated proteins. This suggests
      that kidney aminoacylase may be involved in the salvage of amino acids by
      hydrolyzing acetyl amino acids released from proteins.

PMID- 9518470
TI  - Rapid one-step isolation of mouse liver catalase by immobilized metal ion
      affinity chromatography.
AB  - A novel and rapid procedure for the isolation of catalase from mouse liver, after
      prior treatment with the peroxisome proliferator perfluorooctanoic acid was
      developed using immobilized metal ion affinity chromatography involving chelation
      with zinc ions. The purification developed is simple, rapid (requiring 3 hours
      from cytosol or peroxisomal matrix to homogeneous proteins), reproducible, and
      yields virtually complete overall recovery of catalase activity. This procedure
      makes catalase from a variety of tissues and physiological and environmental
      conditions more readily available for study.

PMID- 9518471
TI  - Expression and purification of epidermal cell differentiation inhibitor (EDIN)
      from Bacillus subtilis.
AB  - The expression of staphylococcal epidermal cell differentiation inhibitor (EDIN),
      an ADP-ribosyltransferase targeting the small GTP-binding protein rho p21, was
      examined using Bacillus subtilis. A recombinant plasmid, containing B.
      licheniformis alpha-amylase promoter flanking either a beta-glucanase or a B.
      cereus sphingomyelinase signal sequence, and a DNA fragment corresponding to
      mature EDIN were constructed and used to transform B. subtilis KN2. Transformants
      were designated ED7 and ED8, respectively. ED7 extracellularly produced
      recombinant protein, which was purified to homogeneity through column
      chromatography using SP-Toyopearl 650 cation-exchange gel and the HA1000
      hydroxyapatite HPLC column. ED8 did not grow in broth culture. Biochemical and
      biological studies of purified protein revealed that ED7 produced a correctly
      processed recombinant EDIN, indistinguishable from natural EDIN.

PMID- 9518472
TI  - Affinity purification of recombinant trypsinogen using immobilized ecotin.
AB  - Affinity purification of inactive precursors (zymogens) of serine proteases on
      protease inhibitor columns is not feasible, due to the weak interaction between
      canonical protease inhibitors and protease zymogens. In this study we demonstrate
      that immobilized ecotin, a unique protease inhibitor from Escherichia coli,
      provides a superior affinity matrix for the purification of trypsinogen and
      possibly other serine protease zymogens as well.

PMID- 9518474
TI  - Public health implications of 1990 air toxics concentrations across the United
      States.
AB  - Occupational and toxicological studies have demonstrated adverse health effects
      from exposure to toxic air contaminants. Data on outdoor levels of toxic air
      contaminants have not been available for most communities in the United States,
      making it difficult to assess the potential for adverse human health effects from
      general population exposures. Emissions data from stationary and mobile sources
      are used in an atmospheric dispersion model to estimate outdoor concentrations of
      148 toxic air contaminants for each of the 60,803 census tracts in the contiguous
      United States for 1990. Outdoor concentrations of air toxics were compared to
      previously defined benchmark concentrations for cancer and noncancer health
      effects. Benchmark concentrations are based on standard toxicological references
      and represent air toxic levels above which health risks may occur. The number of
      benchmark concentrations exceeded by modeled concentrations ranged from 8 to 32
      per census tract, with a mean of 14. Estimated concentrations of benzene,
      formaldehyde, and 1,3-butadiene were greater than cancer benchmark concentrations
      in over 90% of the census tracts. Approximately 10% of all census tracts had
      estimated concentrations of one or more carcinogenic HAPs greater than a 1-in
      10,000 risk level. Twenty-two pollutants with chronic toxicity benchmark
      concentrations had modeled concentrations in excess of these benchmarks, and
      approximately 200 census tracts had a modeled concentration 100 times the
      benchmark for at least one of these pollutants. This comprehensive assessment of
      air toxics concentrations across the United States indicates hazardous air
      pollutants may pose a potential public health problem.

PMID- 9518475
TI  - Impact of organochlorine contamination on levels of sex hormones and external
      morphology of common snapping turtles (Chelydra serpentina serpentina) in
      Ontario, Canada.
AB  - Recent research has suggested that contaminants in the environment may influence
      sex differentiation and reproductive endocrine function in wildlife.
      Concentrations of organochlorine contaminants (total polychlorinated biphenyls,
      pesticides) were higher in the blood plasma of snapping turtles from contaminated
      sites than in those from reference sites. The ratio of the precloacal length to
      the posterior lobe of the plastron (PPR) is sexually dimorphic in snapping
      turtles. There were significant reductions in the PPR at three contaminated sites
      versus two reference sites. The magnitude of the response was such that a
      significantly higher proportion of PPRs of males from a contaminated site (Cootes
      Paradise) overlapped with those of females than PPRs of males from a reference
      site (Lake Sasajewun). Observers can incorrectly identify the sex of turtles at
      the contaminated site based on secondary sexual characteristics alone. Unlike the
      changes to the morphology, there were few changes in 17 beta-estradiol or
      testosterone levels, and where differences occurred, there was more variation
      among reference sites than between the reference and contaminated sites. Our
      results suggest that environmental contaminants may affect sexually dimorphic
      morphology in snapping turtles without affecting circulating testosterone or
      estrogen levels in the adults.

PMID- 9518476
TI  - The protein splicing domain of the homing endonuclease PI-sceI is responsible for
      specific DNA binding.
AB  - The homing endonuclease PI- Sce I consists of a protein splicing domain (I) and
      an endonucleolytic domain (II). To characterize the two domains with respect to
      their contribution to DNA recognition we cloned, purified and characterized the
      isolated domains. Both domains have no detectable endonucleolytic activity.
      Domain I binds specifically to the PI- Sce I recognition sequence, whereas domain
      II displays only weak non-specific DNA binding. In the specific complex with
      domain I the DNA is bent to a similar extent as observed with the initial complex
      formed between PI- Sce I and DNA. Our results indicate that protein splicing
      domain I is also involved in recognition of the DNA substrate.

PMID- 9518477
TI  - Inhibition of DNA polymerase reactions by pyrimidine nucleotide analogues lacking
      the 2-keto group.
AB  - To investigate the influence of the pyrimidine 2-keto group on selection of
      nucleotides for incorporation into DNA by polymerases, we have prepared two C
      nucleoside triphosphates that are analogues of dCTP and dTTP, namely 2-amino-5
      (2'-deoxy-beta-d-ribofuranosyl)pyridine-5'-triphosphate (d*CTP) and 5-(2'-deoxy-
      beta-d-ribofuranosyl)-3-methyl-2-pyridone-5'-triphosphate (d*TTP) respectively.
      Both proved strongly inhibitory to PCR catalysed by Taq polymerase; d*TTP rather
      more so than d*CTP. In primer extension experiments conducted with either Taq
      polymerase or the Klenow fragment of Escherichia coli DNA polymerase I, both
      nucleotides failed to substitute for their natural pyrimidine counterparts.
      Neither derivative was incorporated as a chain terminator. Their capacity to
      inhibit DNA polymerase activity may well result from incompatibility with the
      correctly folded form of the polymerase enzyme needed to stabilize the transition
      state and catalyse phosphodiester bond formation.

PMID- 9518478
TI  - Inhibition of polyadenylation by stable RNA secondary structure.
AB  - The presence of a polyadenylation signal in the repeat (R) region of the HIV-1
      genome, which is located at both the 5' and 3' ends of the viral transcripts,
      requires differential regulation of polyadenylation. The HIV-1 poly(A) site can
      fold in a stable stem-loop structure that is well-conserved among different human
      and simian immunodeficiency viruses. In this study, we tested the effect of this
      hairpin on polyadenylation by introducing mutations that either stabilize or
      destabilize the RNA structure. The HIV-1 sequences were inserted into the pSV2CAT
      reporter plasmid upstream of the SV40 early poly(A) site. These constructs were
      transfected into COS cells and transcripts were analyzed for the usage of the HIV
      1 versus SV40 poly(A) site. The wild-type HIV-1 poly(A) site was used efficiently
      in this context and destabilization of the poly(A) hairpin did not affect the
      polyadenylation efficiency. In contrast, further stabilization of the hairpin
      severely inhibited HIV-1 polyadenylation. Additional mutations that repair the
      thermodynamic stability of this mutant hairpin restored the polyadenylation
      activity. These results indicate that the mechanism of polyadenylation can be
      repressed by stable RNA structure encompassing the poly(A) signal. Experiments
      performed at reduced temperatures also suggest an inverse correlation between the
      stability of the RNA structure and the efficiency of polyadenylation.

PMID- 9518479
TI  - In vitro and in vivo self-cleavage of a viroid RNA with a mutation in the
      hammerhead catalytic pocket.
AB  - Peach latent mosaic viroid (PLMVd) can adopt hammerhead structures in both
      polarity strands. In the course of a study on the variability of this viroid a
      natural sequence variant has been characterized in which the hammerhead structure
      of the plus polarity strand has the sequence CCGA instead of the conserved
      uridine turn motif CUGA present in the catalytic pocket of all natural hammerhead
      structures. The viroid RNA containing this mutant hammerhead structure, but not
      those with the two other possible substitutions, U-->A and U-->G, in the same
      position of the catalytic pocket, showed significant self-cleavage activity
      during in vitro transcription. Moreover, the corresponding full-length PLMVd cDNA
      was infectious and the mutation was retained in a fraction of the viroid progeny.
      These results indicate that the sequence flexibility of the hammerhead structure,
      acting in vitro and in vivo , is higher than anticipated and provide relevant
      data for a deeper insight into the catalytic mechanism of this class of ribozymes
      and into the structure of the uridine turn motif.

PMID- 9518480
TI  - The elongation factor 1 A-2 isoform from rabbit: cloning of the cDNA and
      characterization of the protein.
AB  - Eukaryotic elongation factor 1 A (eEF1A, formerly elongation factor-1 alpha) is
      an important component of the protein synthesis apparatus. Here we report the
      isolation and characterization of the cDNA sequence encoding rabbit eEF1A-2, an
      isoform of eEF1A, as well as a structural and functional comparison of the two
      rabbit isoforms. Northern analysis of the expression pattern of eEF1A-2 showed
      that this isoform is expressed in skeletal muscle, heart, brain and aorta, while
      transcripts are not detected in liver, kidney, spleen and lung. In contrast, the
      previously characterized eEF1A-1 isoform is expressed in all tissues examined
      except skeletal muscle. We have recently purified eEF1A-2 from rabbit skeletal
      muscle. By partial amino acid sequencing and determination of the post
      translational modifications of eEF1A-2 we found that both of the
      glycerylphosphorylethanolamine modifications observed in eEF1A-1 appear to be
      present in eEF1A-2. However, two of the residues found dimethylated in eEF1A-1
      appeared to be trimethylated in eEF1A-2. A comparison of the enzymatic activity
      showed that eEF1A-1 and eEF1A-2 have indistinguishable activity in an in vitro
      translation system. In contrast, the GDP dissociation rate constant is
      approximately 7 times higher for eEF1A-1 than for eEF1A-2. The nucleotide
      preference ratio (GDP/GTP) for eEF1A-1 was 0.82, while the preference ratio for
      eEF1A-2 was 1.50.

PMID- 9518481
TI  - Functional association of poly(ADP-ribose) polymerase with DNA polymerase alpha
      primase complex: a link between DNA strand break detection and DNA replication.
AB  - Poly(ADP-ribose) polymerase (PARP) is an element of the DNA damage surveillance
      network evolved by eukaryotic cells to cope with numerous environmental and
      endogenous genotoxic agents. PARP has been found to be involved in vivo in both
      cell proliferation and base excision repair of DNA. In this study the interaction
      between PARP and the DNA polymerase alpha-primase tetramer has been examined. We
      provide evidence that in proliferating cells: (i) PARP is physically associated
      with the catalytic subunit of the DNA polymerase alpha-primase tetramer, an
      association confirmed by confocal microscopy, demonstrating that both enzymes are
      co-localized at the nuclear periphery of HeLa cells; (ii) this interaction
      requires the integrity of the second zinc finger of PARP and is maximal during
      the S and G2/M phases of the cell cycle; (iii) PARP-deficient cells derived from
      PARP knock-out mice exhibited reduced DNA polymerase activity, compared with the
      parental cells, a reduction accentuated following exposure to sublethal doses of
      methylmethanesulfonate. Altogether, the present results strongly suggest that
      PARP participates in a DNA damage survey mechanism implying its nick-sensor
      function as part of the control of replication fork progression when breaks are
      present in the template.

PMID- 9518482
TI  - DNA fragments with specific nucleotide sequences in their single-stranded termini
      exhibit unusual electrophoretic mobilities.
AB  - DNA restriction fragments, 120-650 base pairs (bp) in length, with 5'-GCGC-3', 5'
      GGCC-3' or 3'-GCGC-5' single-stranded overhanging termini, give rise to diffuse
      bands of unusual electrophoretic mobility in non-denaturing polyacrylamide gels.
      This shift in electrophoretic mobility can be observed at 4-12 degreesC, not at
      higher temperatures, but is stabilized by 5-10 mM Mg2+, even at 37 degreesC. The
      nucleotide sequence in the abutting double-stranded part of the fragment does not
      affect this phenomenon, which is not caused by dimerization. The altered mobility
      may be due to the unusual terminal DNA structure, which is dependent on co
      operative interactions among more than two neighboring G and C residues. The
      structure is stabilized by cytidine methylation. The biological role of such
      fragment structures in DNA repair and recombination is presently unknown.

PMID- 9518484
TI  - Simple and efficient generation in vitro of nested deletions and inversions: Tn5
      intramolecular transposition.
AB  - We have exploited the intramolecular transposition preference of the Tn 5 in
      vitro transposition system to test its effectiveness as a tool for generation of
      nested families of deletions and inversions. A synthetic transposon was
      constructed containing an ori, an ampicillin resistance (Ampr) gene, a multi
      cloning site (MCS) and two hyperactive end sequences. The donor DNA that adjoins
      the transposon contains a kanamycin resistance (Kanr) gene. Any Amprreplicating
      plasmid that has undergone a transposition event (Kans) will be targeted
      primarily to any insert in the MCS. Two different size targets were tested in the
      in vitro system. Synthetic transposon plasmids containing either target were
      incubated in the presence of purified transposase (Tnp) protein and transformed.
      Transposition frequencies (Ampr/Kans) for both targets were found to be 30-50%,
      of which >95% occur within the target sequence, in an apparently random manner.
      By a conservative estimate 10(5) or more deletions/inversions within a given
      segment of DNA can be expected from a single one-step 20 microl transposition
      reaction. These nested deletions can be used for structure-function analysis of
      proteins and for sequence analysis. The inversions provide nested sequencing
      templates of the opposite strand from the deletions.

PMID- 9518483
TI  - DNA bending: the prevalence of kinkiness and the virtues of normality.
AB  - DNA bending in 86 complexes with sequence-specific proteins has been examined
      using normal vector plots, matrices of normal vector angles between all base
      pairs in the helix, and one-digit roll/slide/twist tables. FREEHELIX, a new
      program especially designed to analyze severely bent and kinked duplexes,
      generates the foregoing quantities plus local roll, tilt, twist, slide, shift and
      rise parameters that are completely free of any assumptions about an overall
      helix axis. In nearly every case, bending results from positive roll at
      pyrimidine-purine base pair steps: C-A (= T-G), T-A, or less frequently C-G, in a
      direction that compresses the major groove. Normal vector plots reveal three well
      defined types of bending among the 86 examples: (i) localized kinks produced by
      positive roll at one or two discrete base pairs steps, (ii) three-dimensional
      writhe resulting from positive roll at a series of adjacent base pairs steps, or
      (iii) continuous curvature produced by alternations of positive and negative roll
      every 5 bp, with side-to-side zig-zag roll at intermediate position. In no case
      is tilt a significant component of the bending process. In sequences with two
      localized kinks, such as CAP and IHF, the dihedral angle formed by the three
      helix segments is a linear function of the number of base pair steps between
      kinks: dihedral angle = 36 degrees x kink separation. Twenty-eight of the 86
      examples can be described as major bends, and significant elements in the
      recognition of a given base sequence by protein. But even the minor bends play a
      role in fine-tuning protein/DNA interactions. Sequence-dependent helix
      deformability is an important component of protein/DNA recognition, alongside the
      more generally recognized patterns of hydrogen bonding. The combination of
      FREEHELIX, normal vector plots, full vector angle matrices, and one-digit
      roll/slide/twist tables affords a rapid and convenient method for assessing
      bending in DNA.

PMID- 9518485
TI  - Additive antisense effects of different PNAs on the in vitro translation of the
      PML/RARalpha gene.
AB  - The potential use of peptide nucleic acid (PNA) as a sequence-specific inhibitor
      of RNA translation is investigated in this report. Three different regions of the
      PML/RARalpha oncogene, including two AUG potential start codons, were studied as
      targets of translation inhibition by antisense PNA in a cell-free system. A PNA
      targeted to the second AUG start codon, which was shown previously to be able to
      suppress in vitro translation from that site completely, was used alone or in
      combination with another PNA directed to the first AUG, and a third PNA within
      the 5'-untranslated region (5'-UTR) of mRNA. When used alone, no PNA was able to
      completely block the synthesis of the PML/RARalpha protein. The 5'-UTR PNA was
      the most potent translation inhibitor when used as single agent. However, a near
      complete (>/=90%) specific inhibition of the PML/RARalpha gene was obtained when
      the three PNAs were used in combination, thus obtaining an additive antisense
      effect.

PMID- 9518486
TI  - Essential dynamics of DNA containing a cis.syn cyclobutane thymine dimer lesion.
AB  - Conformational properties of a UV-damaged DNA decamer containing a cis.syn
      cyclobutane thymine dimer (PD) have been investigated by molecular dynamics (MD)
      simulations. Results from MD simulations of the damaged decamer DNA show a kink
      of approximately 21.7 degrees at the PD damaged site and a disruption of H
      bonding between the 5'-thymine of the PD and its complementary adenine. However,
      no extra-helical flipping of the 3'-adenine complementary to the PD was observed.
      Comparison to two undamaged DNA decamers, one with the same sequence and the
      other with an AT replacing the TT sequence, indicates that these properties are
      specific to the damaged DNA. Essential dynamics (ED) derived from the MD
      trajectories of the three DNAs show that the backbone phosphate between the two
      adenines complementary to the PD of the damaged DNA has considerably larger
      mobility than the rest of the molecule and occurs only in the damaged DNA. As
      observed in the crystal structure of T4 endonuclease V in a complex with the
      damaged DNA, the interaction of the enzyme with the damaged DNA can lead to
      bending along the flexible joint and to induction of adenine flipping into an
      extra-helical position. Such motions may play an important role in damage
      recognition by repair enzymes.

PMID- 9518487
TI  - Efficient directional cloning of recombinant adenovirus vectors using DNA-protein
      complex.
AB  - We describe an efficient cloning system utilizing adenoviral DNA-protein
      complexes which allows the directional cloning of genes into adenoviral
      expression vectors in a single step. DNA-protein complexes derived from a
      recombinant adenovirus (AVC2.null) were isolated by sequential use of CsCl step
      gradients followed by isopycnic centrifugation in a mixture of CsCl and guanidine
      HCl. AVC2.null is an adenoviral expression vector containing unique restriction
      sites between the human CMV-IE promoter and the SV40 intron/polyadenylation site.
      Transgenes were prepared for cloning into this vector by introduction of
      compatible restriction sites by PCR. A vector expressing rat granulocyte
      macrophage colony-stimulating factor (GM-CSF) was constructed using DNA-protein
      complex as well as by traditional recombination techniques. The efficacy of our
      adenoviral cloning system utilizing DNA-protein complex was two logs higher than
      that seen using homologous recombination. All viruses generated by directional
      ligation of the insert into the vector DNA-protein complexes contained the
      desired transgene in the correct orientation. This technique greatly simplifies
      and accelerates the generation of recombinant adenoviral vectors.

PMID- 9518488
TI  - Characterization of a polypurine/polypyrimidine sequence upstream of the mouse
      metallothionein-I gene.
AB  - A 128 base pair long homopurine/homopyrimidine (R/Y) element is located
      approximately 1.2 kb upstream of the transcription start point of the mouse
      metallothionein-I ( MT-I ) gene. We present a detailed in vitro structural
      characterization of the MT-I R/Y sequence as determined by enzymatic and chemical
      probes. An approximately 190 bp fragment containing the MT-I R/Y sequence was
      subcloned into a recombinant vector. Low resolution analysis with S1 nuclease
      indicates that DNA in this region was unpaired in supercoiled plasmids treated at
      low pH. High resolution mapping with chemical probes selective for non-B DNA
      structures provides evidence that the MT-I R/Y sequence adopts one or more H-DNA
      structures. We also investigated this sequence to determine if it can influence
      transcriptional regulation. Promoter/reporter constructs were prepared in which
      the MT-I R/Y sequence was positioned in either orientation upstream of either the
      MT-I or HSV-TK promoters. Promoter/reporter activities were evaluated by
      transient transfection assays using mouse NIH3T3 cells. The MT-I R/Y sequence
      displayed no detectable activity as a cis -acting transcriptional regulatory
      element. These results demonstrate that although the MT-I R/Y sequence is able to
      adopt a non-B DNA structure under certain in vitro conditions, there is no
      evidence that this sequence plays a significant role in transcriptional
      regulation.

PMID- 9518489
TI  - The -104G nucleotide of the human CYP21 gene is important for CYP21 transcription
      activity and protein interaction.
AB  - CYP21 gene encodes the steroid 21-hydroxylase (P450c21) that is involved in
      steroidogenesis in the adrenal cortex. Mutations occurring on CYP21 which convert
      it to the neighboring pseudogene, CYP21P, are found in patients with congenital
      adrenal hyperplasia (CAH), an autosomal recessive disease. We previously reported
      that the CYP21P pseudogene had lower transcription activity when compared with
      the active CYP21 gene. The sequences determining the basal transcription activity
      of the human CYP21 gene are located within the 166 bp region upstream from the
      transcriptional start site. Within this region, only 4 nucleotides are different
      between the active CYP21 and the CYP21P pseudogene; they are located at the -117,
      -104, -101 and -94 positions from the start site of the gene. Here, we report
      that the CYP21 gene-specific G nucleotide sequence at the -104 position is
      required for its basal transcription activity driven by the native TATA box of
      the human CYP21 gene. When this single nucleotide is changed to the CYP21P
      sequence, the basal transcription activity decreases by approximately 80% in
      transient transfection assay. In addition, our data from gel retardation assay
      show that this sequence is also critical for interaction with nuclear proteins
      from adrenal cells. These results therefore suggest that the single G sequence of
      the human CYP21 gene is crucial for the expression of its basal transcription
      activity, and this may be influenced by the interaction with specific nuclear
      proteins from the adrenal gland.

PMID- 9518491
TI  - The use of sequence comparison to detect 'identities' in tRNA genes.
AB  - We have developed a computational method that detects 'identities' in tRNA genes
      by using principal component analysis to classify the sequences of bases in tRNA
      genes into groups of similar sequences and then comparing the distribution of
      sequences of bases, in order to extract characteristic bases that are conserved
      within a group but differ between groups. These classification and comparison
      procedures are applied recursively to classify the sequences into hierarchical
      groups, so that multiple levels of characteristic sites can be detected. By using
      this computational method, we were able to detect many characteristic sites in
      the T and D domains of tRNAs, as well as the characteristic sites that had
      already been detected experimentally. This suggests that bases not only in the
      contact regions but also in the elbow regions, which determine the structure and
      dynamics of the whole tRNA molecule, are important to the tRNA-aminoacyl tRNA
      synthetase recognition.

PMID- 9518492
TI  - Mismatched nucleotides may facilitate expansion of trinucleotide repeats in
      genetic diseases.
AB  - We have studied the contribution of mismatch sequences to the trinucleotide
      repeat expansion that causes hereditary diseases. Using an oligonucleotide
      duplex, (CAG)5/(CTG)5, as a template-primer, DNA synthesis was carried out using
      either Escherichia coli DNA polymerase I (Klenow fragment) or human
      immunodeficiency virus type I reverse transcriptase (HIV-RT). Both enzymes
      expanded the repeat sequence longer than 27 nucleotides (nt), beyond the maximum
      length expected from the template size. The expansion was observed under
      conditions in which extension occurs either in both strands or in one strand. In
      contrast, with another template-primer that contains a non-repetitive flanking
      sequence 5'-upstream of the repetitive sequence, the reaction products were not
      extended beyond the template size (45 nt) by these DNA polymerases. We then used
      mismatched template-primers, in which either 1, 2 or 6 non-complementary
      nucleotides were introduced to the repeat sequence that is flanked by a non
      repetitive sequence. In this case, primers were efficiently expanded over the
      expected length of 45 nt, in a mismatch-dependent manner. One of the primers with
      six mismatches extended as long as 72 nt. These results imply that the
      misincorporation of non-complementary deoxyribonucleoside monophosphates (dNMPs)
      into the repeat sequence makes double-stranded DNA unstable and triggers the
      slippage and expansion of trinucleotide repeats by forming loops or hairpin
      structures during DNA synthesis.

PMID- 9518490
TI  - Molecular and biochemical characterisation of DNA-dependent protein kinase
      defective rodent mutant irs-20.
AB  - The catalytic subunit of the DNA-dependent protein kinase (DNA-PKcs) is a member
      of a sub-family of phosphatidylinositol (PI) 3-kinases termed PIK-related
      kinases. A distinguishing feature of this sub-family is the presence of a
      conserved C-terminal region downstream of a PI 3-kinase domain. Mutants defective
      in DNA-PKcs are sensitive to ionising radiation and are unable to carry out V(D)J
      recombination. Irs-20 is a DNA-PKcs-defective cell line with milder gamma-ray
      sensitivity than two previously characterised mutants, V-3 and mouse scid cells.
      Here we show that the DNA-PKcs protein from irs-20 cells can bind to DNA but is
      unable to function as a protein kinase. To verify the defect in irs-20 cells and
      provide insight into the function and expression of DNA-PKcs in double-strand
      break repair and V(D)J recombination we introduced YACs encoding human and mouse
      DNA-PKcs into defective mutants and achieved complementation of the defective
      phenotypes. Furthermore, in irs-20 we identified a mutation in DNA-PKcs that
      causes substitution of a lysine for a glutamic acid in the fourth residue from
      the C-terminus. This represents a strong candidate for the inactivating mutation
      and provides supportive evidence that the extreme C-terminal motif is important
      for protein kinase activity.

PMID- 9518493
TI  - A trypanosome metacyclic VSG gene promoter with two functionally distinct, life
      cycle stage-specific activities.
AB  - In the mammalian bloodstream, African trypanosomes express the variant surface
      glycoprotein (VSG), continual switching of which allows evasion of the host
      immune response. Bloodstream VSG genes are transcribed from polycistronic
      bloodstream expression sites with promoters which are located 45-60 kb upstream.
      These promoters are not exclusively stage-regulated, being active in the insect
      midgut stage where VSG is not expressed. However, the metacyclic VSG (M-VSG)
      genes, a small subset activated when VSG synthesis begins in the metacyclic stage
      in the tsetse fly salivary glands, are transcriptionally activated specifically
      in that stage from promoters <3 kb upstream. Using deletion mapping and transient
      transfection, we show that the entire 1.22 M-VSG gene promoter region (171 bp) is
      required for full activity in metacyclic-derived trypanosomes. However, a
      subsidiary, bloodstream stage-specific activity is present in its 5' half which
      directs transcription initiation very close to the initiation site used in
      metacyclic-derived trypanosomes. Our results imply that the M-VSG gene promoter
      is longer and more complex than other VSG gene promoters.

PMID- 9518495
TI  - A high throughput method to investigate oligodeoxyribonucleotide hybridization
      kinetics and thermodynamics.
AB  - We describe a high throughput microtiter-based assay to measure binding of
      oligodeoxyribonucleotides to nucleic acid targets. The assay utilizes
      oligodeoxyribonucleotide probes labeled with a highly chemiluminescent acridinium
      ester (AE). Reaction of AE with sodium sulfite renders it non-chemiluminescent.
      When an AE-labeled probe hybridizes to a target nucleic acid AE is protected from
      reaction with sodium sulfite and thus remains chemiluminescent. In contrast,
      unhybridized probe readily reacts with sodium sulfite and is rendered non
      chemiluminescent. Hybridization of an AE-labeled probe to a target nucleic acid
      can therefore be detected without physical separation of unhybridized probe by
      treatment of the hybridization reaction with sodium sulfite and measurement of
      the remaining chemiluminescence. Using this method we measured hybridization rate
      constants and thermodynamic affinities of oligodeoxyribonucleotide probes binding
      to simple synthetic targets as well as large complex biological targets. The
      kinetic and thermodynamic parameters were measured with a high degree of accuracy
      and were in excellent agreement with values measured by other established
      techniques.

PMID- 9518494
TI  - NMR evidence for a base triple in the HIV-2 TAR C-G.C+ mutant-argininamide
      complex.
AB  - Formation of a specific complex between the HIV Tat protein and the small RNA
      element TAR is critical for activation of viral transcription. A model complex
      for this interaction composed of HIV-2 TAR and the amide derivative of arginine
      has been developed to study how Tat and TAR interact specifically. We have
      previously determined a high resolution NMR structure of the HIV-2 TAR
      argininamide complex. The argininamide guanidium group hydrogen bonds to the
      major groove face of G26 and is stacked between U23 and A22, forming an arginine
      sandwich. This structure also provided evidence for formation of a U38-A27.U38
      base triple, as U23 is positioned in the major groove within hydrogen bonding
      distance to A27. However, the expected U23 imino proton was not observed,
      preventing unambiguous identification of the base triple. Previous work on an
      isomorphic C38-G27.C23+ base triple mutant of the three base bulge HIV-1 TAR
      argininamide complex demonstrated that the base triple is required for specific
      argininamide binding. Here we investigate the same C38-G27.C23+ base triple
      mutant in the context of two base bulge HIV-2 TAR. The improved NMR spectral
      properties of HIV-2 TAR allowed observation of the C23 amino and imino protons
      for the first time, providing direct evidence that a hydrogen bonding interaction
      is occurring. The NOEs observed correspond to those observed in the high
      resolution structure of the HIV-2 TAR-argininamide complex, confirming that a
      base triple is an important feature of the TAR-argininamide interaction.

PMID- 9518496
TI  - Up-regulation of base excision repair correlates with enhanced protection against
      a DNA damaging agent in mouse cell lines.
AB  - DNA polymerase beta is required in mammalian cells for the predominant pathway of
      base excision repair involving single nucleotide gap filling DNA synthesis. Here
      we examine the relationship between oxidative stress, cellular levels of DNA
      polymerase beta and base excision repair capacity in vitro , using mouse
      monocytes and either wild-type mouse fibroblasts or those deleted of the DNA
      polymerase beta gene. Treatment with an oxidative stress-inducing agent such as
      hydrogen peroxide, 3-morpholinosydnonimine, xanthine/xanthine oxidase or
      lipopolysaccharide was found to increase the level of DNA polymerase beta in both
      monocytes and fibroblasts. Base excision repair capacity in vitro , as measured
      in crude cell extracts, was also increased by lipopolysaccharide treatment in
      both cell types. In monocytes lipopolysaccharide-mediated up-regulation of the
      base excision repair system correlated with increased resistance to the
      monofunctional DNA alkylating agent methyl methanesulfonate. By making use of a
      quantitative PCR assay to detect lesions in genomic DNA we show that
      lipopolysaccharide treatment of fibroblast cells reduces the incidence of
      spontaneous DNA lesions. This effect may be due to the enhanced DNA polymerase
      beta-dependent base excision repair capacity of the cells, because a similar
      decrease in DNA lesions was not observed in cells deficient in base excision
      repair by virtue of DNA polymerase beta gene deletion. Similarly, fibroblasts
      treated with lipopolysaccharide were more resistant to methyl methanesulfonate
      than untreated cells. This effect was not observed in cells deleted of the DNA
      polymerase beta gene. These results suggest that the DNA polymerase beta
      dependent base excision repair pathway can be up-regulated by oxidative stress
      inducing agents in mouse cell lines.

PMID- 9518497
TI  - Skipper, an LTR retrotransposon of Dictyostelium.
AB  - The complete sequence of a retrotransposon from Dictyostelium discoideum , named
      skipper , was obtained from cDNA and genomic clones. The sequence of a nearly
      full-length skipper cDNA was similar to that of three other partially sequenced
      cDNAs. The corresponding retrotransposon is represented in approximately 15-20
      copies and is abundantly transcribed. Skipper contains three open reading frames
      (ORFs) with an unusual sequence organization, aspects of which resemble certain
      mammalian retroviruses. ORFs 1 and 3 correspond to gag and pol genes; the second
      ORF, pro, corresponding to protease, was separated from gag by a single stop
      codon followed shortly thereafter by a potential pseudoknot. ORF3 (pol) was
      separated from pro by a +1 frameshift. ORFs 2 and 3 overlapped by 32 bp. The
      computed amino acid sequences of the skipper ORFs contain regions resembling
      retrotransposon polyprotein domains, including a nucleic acid binding protein,
      aspartyl protease, reverse transcriptase and integrase. Skipper is the first
      example of a retrotransposon with a separate pro gene. Skipper is also novel in
      that it appears to use stop codon suppression rather than frameshifting to
      modulate pro expression. Finally, skipper and its components may provide useful
      tools for the genetic characterization of Dictyostelium.

PMID- 9518498
TI  - Phosphorothioate oligodeoxyribonucleotides dissociate from cationic lipids before
      entering the nucleus.
AB  - Antisense oligonucleotides complementary to specific mRNA sequences are widely
      used inhibitors of gene expression in vitro and in vivo . In vitro cationic
      lipids have been demonstrated to increase the pharmacological activity of
      antisense oligonucleotides by increasing cellular uptake and facilitating nuclear
      accumulation. We have investigated the intracellular fate of
      oligonucleotide/cationic lipid complexes using fluorescently labeled lipids and
      oligonucleotides targeted to protein kinase C-alpha. After addition to cells the
      lipids initially co-localized with the oligonucleotide on the cell surface and in
      fine punctate structures within the cytoplasm. At later times the oligonucleotide
      began to accumulate in the nucleus as well as the cytoplasm. In contrast, the
      cationic lipid remained localized to the cell surface and the cytoplasm and was
      never found in the nucleus. Expression of protein kinase C-alpha mRNA did not
      begin to decline until after oligonucleotide was seen in the nucleus. This was
      also coincident with the transient appearance of a smaller mRNA transcript
      believed to result from RNase H cleavage of protein kinase C-alpha mRNA. These
      data suggest that although cationic lipids facilitate uptake of oligonucleotides,
      the complex must disassociate before the oligonucleotide can gain access to the
      nucleus and induce degradation of targeted mRNA.

PMID- 9518500
TI  - Multiple isoform recovery (MIR)-PCR: a simple method for the isolation of related
      mRNA isoforms.
AB  - We present a rapid and efficient method for the detection of related transcripts
      with different expression levels. This approach combines the rapid amplification
      of cDNA ends (RACE) method with a cDNA subtractive technique. The strategy is
      based on successive subtractions of prevalent isoforms resulting in enrichment of
      less expressed transcripts. For each subtraction, a biotinylated primer specific
      for the prevalent isoform is hybridized on the total cDNA and the hybrid is
      retained on a streptavidin affinity column. The unbound cDNA serves as a template
      for subsequent isoform identification. To illustrate its application we describe
      the isolation of three new actin cDNA isoforms in the freshwater planarian
      Dugesia (S) polychroa.

PMID- 9518501
TI  - Detection of programmed cell death using fluorescence energy transfer.
AB  - Fluorescence energy transfer (FRET) can be generated when green fluorescent
      protein (GFP) and blue fluorescent protein (BFP) are covalently linked together
      by a short peptide. Cleavage of this linkage by protease completely eliminates
      FRET effect. Caspase-3 (CPP32) is an important cellular protease activated during
      programmed cell death. An 18 amino acid peptide containing CPP32 recognition
      sequence, DEVD, was used to link GFP and BFP together. CPP32 activation can be
      monitored by FRET assay during the apoptosis process.

PMID- 9518499
TI  - Cr(III)-mediated crosslinks of glutathione or amino acids to the DNA phosphate
      backbone are mutagenic in human cells.
AB  - Carcinogenic Cr(VI) compounds were previously found to induce amino
      acid/glutathione-Cr(III)-DNA crosslinks with the site of adduction on the
      phosphate backbone. Utilizing the pSP189 shuttle vector plasmid we found that
      these ternary DNA adducts were mutagenic in human fibroblasts. The Cr(III)
      glutathione adduct was the most potent in this assay, followed by Cr(III)-His and
      Cr(III)-Cys adducts. Binary Cr(III)-DNA complexes were only weakly mutagenic,
      inducing a significant response only at a 10 times higher number of adducts
      compared with Cr(III)-glutathione. Single base substitutions at the G:C base
      pairs were the predominant type of mutations for all Cr(III) adducts. Cr(III),
      Cr(III)-Cys and Cr(III)-His adducts induced G:C-->A:T transitions and G:C-->T:A
      transversions with almost equal frequency, whereas the Cr(III)-glutathione
      mutational spectrum was dominated by G:C-->T:A transversions. Adduct-induced
      mutations were targeted toward G:C base pairs with either A or G in the 3'
      position to the mutated G, while spontaneous mutations occurred mostly at G:C
      base pairs with a 3' A. No correlation was found between the sites of DNA
      adduction and positions of base substitution, as adducts were formed randomly on
      DNA with no base specificity. The observed mutagenicity of Cr(III)-induced
      phosphotriesters demonstrates the importance of a Cr(III)-dependent pathway in
      Cr(VI) carcinogenicity.

PMID- 9518502
TI  - The effect of ionic strength on the kinetics of rigor development in skinned fast
      twitch skeletal muscle fibres.
AB  - Recent atomic 3-D reconstructions of the acto-myosin interface suggest that
      electrostatic interactions are important in the initial phase of cross-bridge
      formation. Earlier biochemical studies had also given strong evidence for the
      ionic strength dependence of this step in the cross-bridge cycle. We have probed
      these interactions by altering the ionic strength (Gamma/2) of the medium mainly
      with K+, imidazole+ and EGTA2- to vary charge shielding. We examined the effect
      of ionic strength on the kinetics of rigor development at low Ca2+ (experimental
      temperature 18-22 degrees C) in chemically skinned single fast-twitch fibres of
      mouse extensor digitorum longus (EDL) muscle. On average the delay before rigor
      onset was 10 times longer, the maximum rate of rigor tension development was 10
      times slower, the steady-state rigor tension was 3 times lower and the in-phase
      stiffness was 2 times lower at high (230 mM) compared to low (60 mM) ionic
      strength. These results were modelled by calculating ATP depletion in the fibre
      due to diffusional loss of ATP and acto-myosin Mg.ATPase activity. The difference
      in delay before rigor onset at low and high ionic strength could be explained in
      our model by assuming a 15 times higher Mg.ATPase activity and a threefold
      increase in Km in relaxing conditions at low ionic strength. Activation by Ca2+
      induced at different time points before and during onset of rigor confirmed the
      calculated time course of ATP depletion. We have also investigated ionic strength
      effects on rigor development with the activated troponin/tropomyosin complex. ATP
      withdrawal at maximum activation by Ca2+ induced force transients which led into
      a "high rigor" state. The peak forces of these force transients were very similar
      at low and high ionic strength. The subsequent decrease in tension was only 10%
      slower and steady-state "high rigor" tension was reduced by only 27% at high
      compared to low ionic strength. Addition of 10 mM phosphate to lower cross-bridge
      attachment strongly suppressed the transient increases in force at high ionic
      strength and reduced the steady-state rigor tension by 17%. A qualitatively
      similar but smaller effect of phosphate was observed at low ionic strength where
      steady-state rigor force was reduced by 10%. The data presented in this study
      show a very strong effect of ionic strength on rigor development in relaxed
      fibres whereas the ionic strength dependence of rigor development after thin
      filament activation was much less. The data confirm the importance of
      electrostatic interactions in cross-bridge attachment and cross-bridge-attachment
      induced activation of thin filaments.

PMID- 9518503
TI  - Decreasing diffusion limitation on exercise in lower-graded interstitial lung
      disease.
AB  - In this study we investigated the contribution of diffusion limitation to the
      exercise-induced hypoxaemia in interstitial lung disease (ILD). We applied
      isotopic analysis to the composition of the stable isotopic oxygen molecules 16O2
      and 16O18O in expiratory gas mixtures obtained from six ILD patients and six
      healthy subjects at rest and during ergometer work (60 W). The changes in the
      16O18O/16O2 ratios were interpreted by using the overall fractionation factor of
      respiration (alpha O) which would be increased towards 1.03 on increasing
      diffusion limitation. In addition, the O2 partial pressures of alveolar gas and
      arterial blood (PAO2, PaO2) were determined. In the patients, alpha O was
      significantly reduced from 1.0066 +/- 0.0004 (mean +/- SD) at rest to 1.0035 +/-
      0.0004 during exercise and in the healthy subjects from 1.0072 +/- 0.0008 to
      1.0044 +/- 0.0004. Furthermore, the exercise-induced reduction of PaO2 (from 77
      to 69 mmHg) was due to a drop of alveolar PO2 found in each patient, whereas in
      each healthy subject PaO2 was increased on exercise. On the basis of a resistance
      model we conclude that the patients' data were inconsistent with increasing
      diffusion limitation but showed an increasing impairment of O2 transport by
      ventilation.

PMID- 9518505
TI  - A regulated environmental perfusion system for the study of anoxic or hypoxic
      cultured neurons using microfluorescence imaging and electrophysiology.
AB  - We describe the design and performance of a newly developed regulated
      environmental perfusion system (REPS). This system allows study of the effects of
      anoxia or hypoxia in cultured cells at physiological temperature, without the use
      of oxygen-scavenging compounds or metabolic inhibitors. The REPS incorporates a
      "canoe-shaped" flow-through chamber with access from above to allow positioning
      of pipettes for patch-clamp, microinjection, rapid-application perfusion, or
      microprobes for monitoring physical parameters. The combination of laminar flow
      and complete washout of perfusate within the chamber, and the use of a gas-tight
      perfusate delivery system and pressurized reservoirs containing media with pre
      stabilized oxygen tensions (pO2 values) allow rapid production of accurate
      perfusate pO2 within the chamber. Perfusate pO2 in the chamber declined
      monoexponentially with time constants of </= 20 s to stable, pre-determined
      levels of 0 or 2 kPa (15 Torr). Shielding the gas/liquid interface of the chamber
      with an argon curtain only minimally decreased time constants at flow rates >/= 2
      ml/min. The perfusion chamber of the REPS is easily mounted on the stage of an
      inverted microscope, for use with fluorescence imaging or electrophysiological
      studies of cultured cells. In tests with cultured rat cortical neurons,
      intracellular calcium concentration increased exponentially to values exceeding 1
      microM during 10 min of anoxic insult, and returned to baseline values within 1
      min after restoring normoxia.

PMID- 9518504
TI  - The effect of exhaustive exercise on the antioxidant enzyme system in skeletal
      muscle from calcium-deficient rats.
AB  - The aim of the current study was to elucidate the synergism of dietary calcium
      restriction and exhaustive exercise in the antioxidant enzyme system of rat
      soleus muscle, and to investigate the involvement of neutrophils in exercise
      induced muscle damage. Forty-eight male Wistar rats were assigned to the
      following groups: control (C) or calcium-restricted [1 month (1 M) or 3 months (3
      M)]. Each group was subdivided into acutely exercised or non-exercised groups.
      Soleus muscle from each rat was analysed to determine the levels of antioxidant
      enzymes [Mn-superoxide dismutase (SOD), Cu, Zn-SOD, glutathione peroxidase (GPX),
      and catalase (CAT)]. Dietary calcium restriction resulted in calcium deficiency
      and upregulated the antioxidant enzymes examined except GPX. Conversely,
      exhaustive exercise significantly decreased GPX and CAT, but not SODs activities
      in the calcium-restricted (1 M and/or 3 M) rats. Contents of immunoreactive Mn
      SOD and Cu,Zn-SOD were only increased in the 3 M rats. During calcium
      restriction, the mRNA expression of both forms of SOD showed initial
      upregulation, followed by downregulation. Exhaustive exercise significantly
      increased the mRNA expressions only in the 3 M rats. Moreover, exhaustive
      exercise markedly increased myeloperoxidase activity in soleus muscles from the 1
      M and 3 M rats compared with the C rats, and significantly enhanced the ability
      of neutrophils to generate superoxide in the 3 M rats. The results demonstrate
      that dietary calcium restriction upregulates certain antioxidant enzyme
      activities in rat soleus muscle, indicating an enhanced resistance to potential
      increases in intracellular reactive oxygen species. The results also suggest that
      exhaustive exercise may cause oxidative damage in soleus muscle of calcium
      deficient rats through the activation of neutrophils.

PMID- 9518506
TI  - Calcium channel current facilitation in porcine adrenal chromaffin cells.
AB  - The mechanisms of depolarizing-prepulse-induced facilitation of Ca2+ channel
      current were investigated in a study of porcine chromaffin cells. The Ba2+
      current evoked by a pulse to 0 mV was increased by a strong depolarizing prepulse
      (conditioning pulse), termed "facilitation". This facilitation increased with an
      increase in either the duration or the voltage of the conditioning pulse, and
      decreased with an increase in the interpulse interval. For example, the Ba2+
      current was increased to 1.14 times the control (facilitation ratio) by a 150-ms
      conditioning pulse to +100 mV followed by a 10-ms interpulse interval. Forskolin,
      8-bromo-adenosine 3',5'-cyclic monophosphate (8-bromo-cAMP) and Rp-adenosine
      3',5'-cyclic monophosphothioate (Rp-cAMPS) did not affect the facilitation of the
      Ba2+ current, suggesting that a cAMP-dependent mechanism is not involved.
      Intracellular guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) decreased the
      Ba2+ current to 0.59 times the control and GDP beta S increased it to 1.19.
      However, neither GTP gamma S nor guanosine 5'-O-(2-thiodiphosphate) (GDP beta S)
      changed the amplitude of the Ba2+ current that was facilitated by the
      conditioning pulse. Thus, GTP gamma S increased the facilitation ratio to 2.05
      and GDP beta S decreased it to 1.05. Furthermore, the facilitation of the Ba2+
      current was abolished by omega-conotoxin GVIA but not by either omega-agatoxin
      IVA or nifedipine. These results suggest that, in porcine chromaffin cells, there
      is a omega-conotoxin GVIA-sensitive N-type Ca2+ channel that is under the
      inhibitory control of a G protein, which can be relieved by a conditioning pulse.

PMID- 9518507
TI  - Influence of postnatal changes in action potential duration on Na-Ca exchange in
      rabbit ventricular myocytes.
AB  - Cardiac Na-Ca exchanger (NCX) expression and current density are significantly
      greater in newborn rabbit hearts compared with adults. However, the relatively
      short action potential (AP) at birth may limit the impact of increased NCX
      expression by diminishing Ca2+ entry via Na-Ca exchange current (INaCa). To
      address the interdependence of AP duration and NCX activity, we voltage-clamped
      newborn (NB, 1-5 day), juvenile (JV, 10-14 day) and adult (AD) rabbit myocytes
      with a series of APs of progressively increasing duration (APD90: 108-378 ms)
      under nominally chloride-free conditions. In each age group we quantified an
      increase in outward (QExout) and inward (QExin) Ni2+-sensitive charge movement in
      response to AP prolongation. QExout and QExin measured during age-appropriate APs
      declined postnatally [QEXout: NB (2 day) 0.19 +/- 0.02, JV (10 day) 0.10 +/-
      0.01, AD 0.04 +/- 0.002; QEXin: NB -0. 2 +/- 0.01, JV -0.11 +/- 0.02; AD -0.04 +/
      0.003 pC/pF] despite the significantly shorter APD90 of newborn myocytes (NB 122
      +/- 10; AD 268 +/- 22 ms). When Ca2+ fluxes by other transport pathways were
      blocked with nifedipine, ryanodine and thapsigargin, age-appropriate APs elicited
      contractions in NB and JV but not AD myocytes (NB 4.8 +/- 0.5, JV 1.2 +/- 0.3%
      resting length). These data demonstrate that a shorter AP does not negate the
      impact of increased NCX expression at birth.

PMID- 9518508
TI  - Calcium-activated chloride conductance in a pancreatic adenocarcinoma cell line
      of ductal origin (HPAF) and in freshly isolated human pancreatic duct cells.
AB  - Using the whole-cell patch-clamp technique, a calcium-activated chloride
      conductance (CACC) could be elicited in HPAF cells by addition of 1 microM
      ionomycin to the bath solution (66 +/- 22 pA/pF;Vm + 60 mV) or by addition of 1
      microM calcium to the pipette solution (136 +/- 17 pA/pF; Vm + 60 mV). Both
      conductances had similar biophysical characteristics, including time-dependent
      inactivation at hyperpolarising potentials and a linear/slightly outwardly
      rectifying current/voltage (I/V) curve with a reversal potential (Erev) close to
      the calculated chloride equilibrium potential. The anion permeability sequence
      obtained from shifts in Erev was I > Br >/= Cl. 4,4'-Diisothiocyanatostilbene
      disulphonic acid (DIDS, 500 microM) caused a 13% inhibition of the current (Vm +
      60 mV) while 100 microM glibenclamide, 30 nM TS-TM-calix[4]arene and 10 microM
      tamoxifen, all chloride channel blockers, had no marked effects (8%, -6% and -2%
      inhibition respectively). Niflumic acid (100 microM) caused a voltage-dependent
      inhibition of the current of 48% and 17% (Vm +/- 60 mV, respectively). In freshly
      isolated human pancreatic duct cells (PDCs) a CACC was elicited with 1 microM
      calcium in the pipette solution (260 +/- 62 pA/pF; Vm + 60 mV). The presence of
      this CACC in human PDCs could provide a possible therapeutic pathway for
      treatment of pancreatic insufficiency of the human pancreas in cystic fibrosis.

PMID- 9518509
TI  - Striated muscle calcium-stimulated cysteine protease (calpain-like) activity
      promotes myeloperoxidase activity with exercise.
AB  - An inflammatory response triggered by neutrophil accumulation into muscle tissue
      is thought to occur with exercise-induced muscle damage. To investigate the
      relationship between Ca2+-stimulated proteolysis (calpain-like activity) and
      neutrophil accumulation [myeloperoxidase (MPO) activity], cardiac and plantaris
      muscles from rats (n = 10) completing 1 h exercise (25 m/min) were investigated.
      Exercise promoted increases (P<0.05) in both calpain-like and MPO activities;
      ranging from 2.79 to 58.9 U/g wet weight (ww) and 0.03 to 4.88 U/g ww
      respectively. Pearson's correlational analysis (r) on calpain-like and MPO
      activities for cardiac and plantaris muscle data were 0.97 (P<0.001) and 0.68
      (P<0.05) respectively, with a combined r of 0.83 (P<0.001) for both muscles
      across all conditions. To investigate further the extent to which calpain-like
      activity may promote neutrophil accumulation, another exercise group (n = 5) was
      pre-injected with the cysteine protease inhibitor, E64c, 1 h before exercise.
      Administration of E64c lowered calpain-like and MPO activities by 66% and 56%
      respectively (average from both muscles). From these results it is concluded that
      a relationship exists between Ca2+-stimulated proteolysis and neutrophil
      accumulation into striated muscle with exercise, and that the calpain system is
      involved in localizing the neutrophilic response with exercise.

PMID- 9518510
TI  - The in vivo relationship between blood flow, contractions, pH and metabolites in
      the rat uterus.
AB  - Little is known about the relationship between smooth muscle contractile activity
      and its blood supply. We have therefore investigated this in the rat uterus,
      using laser-Doppler flow measurement and intra-uterine pressure recordings. We
      found an inverse linear relationship between flow and contractile activity. There
      was no evidence for a critical level of flow, above which function is maintained
      and below which it declines; even small reductions in blood flow decreased
      uterine force. Force was rapidly restored upon reperfusion. Reactive hyperaemia
      was absent from all but 6 of the 41 preparations studied. We used 31P nuclear
      magnetic resonance (NMR) spectroscopy to measure concentrations of adenosine
      triphosphate (ATP), phosphocreatine (PCr), inorganic phosphate (Pi) and
      intracellular pH (pHi) simultaneously with force and flow. Reductions in flow
      were associated with significant reductions in [ATP], [PCr] and pHi, and an
      increase in [Pi]. These changes were related to flow significantly and linearly
      and their effects on force may be additive. These data show that uterine smooth
      muscle is closely dependent upon its blood supply for maintaining both normal
      force production and metabolite levels. Consequently, even small decrements in
      flow may have deleterious functional effects.

PMID- 9518511
TI  - Weakening of ion-channel interactions of Na+ and Li+ in acetylcholine-receptor
      channels of frog skeletal muscle with an increase in agonist concentration.
AB  - The possibility that increases in agonist concentration beyond threshold levels
      may force changes in the character of high-conductance open states of skeletal
      muscle nicotinic acetylcholine receptor channels (nAChR) was examined by seeing
      whether differences in several critical ionic properties of nAChR currents could
      be detected with changes in agonist level. Single- and bi-ionic whole-cell
      currents of Na+ and Li+ in voltage-clamped frog (Rana pipiens) muscle fibers were
      measured during local superfusion of endplates with carbamylcholine (carb) at
      concentrations of 54 microm (low-carb) and 270 microM (high-carb). Three ionic
      properties that would be affected by changes in the open-state configuration of
      channel subunits were tested. First, ion-saturation characteristics. Peak Na+ and
      Li+ currents in low-carb trials showed sublinear dependence on ion concentrations
      from 0 to 60 mM with Km values of 78 (Na+) and 49 (Li+) mM and a power function
      slope of 0. 75 on double-log plot. In contrast, the concentration dependence of
      Na+ and Li+ currents in high-carb tests was linear through the origin with a
      power function slope of 1.02. Second, Na+/Li+ selectivity. The ratio of peak Na+
      and Li+ currents in low-carb tests varied from 1.86 to 2.28 for ion
      concentrations of from 20 to 60 mM [mean = 2.02 +/- 0.06 (SEM)] whereas the ratio
      for high-carb trials ranged from only 1.29 to 1.52 [mean = 1.42 +/- 0.40 (SEM)].
      Third, competitive interactions of Na+ and Li+ currents. Equimolar mixtures of
      Na+ and Li+ in low-carb tests produced bi-ionic inward currents which were never
      larger than the single-ion Na+ current alone, but bi-ionic currents at the high
      carb level were always greater than the single-ion Na+ current, approximating the
      sum of the single-ion Na+ and Li+ currents in most cases. The results are
      consistent with a decrease in ion-channel binding at the high-carb level and
      support the possibility of agonist-induced changes in the high-conductance open
      state configuration of nAChR subunits which result in a weakening of constraints
      on cation movements through the channel.

PMID- 9518512
TI  - Kinetics of rhodopsin regeneration in situ and in the excised median eye of
      Limulus polyphemus measured using electrophysiological methods.
AB  - The reactivation of rhodopsin after photoregeneration from metarhodopsin in the
      UV-sensitive cells of the median eye of Limulus was examined by means of
      extracellular electroretinogram (ERG) measurements. Absorbed photons convert the
      transducing rhodopsin (Rt) to metarhodopsin, which is thermostable and can be
      reconverted by another photon to non-transducing rhodopsin (Rn). The amplitude of
      the ERG is assumed to correlate linearly with the amount of Rt under otherwise
      constant conditions. The results demonstrate that the reactivation of Rn recorded
      in vivo in the intact animal is much faster than that in the excised eye [half
      period: 4 min (in vivo), 24 min (excised eye)]. In the excised eye the ERG
      amplitudes recover over a sigmoidal time course; however, in vivo the kinetics
      often appear to be exponential. The in vivo kinetics were measured by several
      defined molar ratios of Rn to rhodopsin plus metarhodopsin [Rn/(R + M)]. These
      were adjusted by different durations of pre-illumination with UV light, which is
      preferentially absorbed by rhodopsin. The in vivo kinetics were fitted by a
      single exponential function. At very high molar ratios of Rn (> 90%) the kinetics
      become sigmoidal even in the in vivo experiments. The half-life of the in vivo
      kinetics depends linearly on the initial molar Rn/(R + M) ratio [half-life: 4-12
      min with a rise of 0.1 min/% inactivated metarhodopsin (Mn), 20 degrees C]. The
      results are consistent with the assumption of multiple-step dephosphorylation
      being the rate-limiting step in regeneration of rhodopsin in the dark.

PMID- 9518514
TI  - In situ characterization of oxalate transport across the basolateral membrane of
      the proximal tubule.
AB  - Oxalate transport across the contraluminal membrane of the proximal tubule was
      studied in vivo using the "capillary stopped flow microperfusion method"
      (Pflugers Arch 400:250-256, 1984). Cellular uptake of oxalate was characteristic
      of a carrier-mediated transport process (Jmax = 1.6 +/- 0.6 pmol/s per cm
      proximal tubular length, Km = 2.03 +/- 0.77 mmol/l). Sulphate inhibited oxalate
      transport in a dose-dependent manner (Ki-value = 1.53 +/- 0.38 mmol/l). Sulphate
      transport across the basolateral membrane was also characteristic of a carrier-
      mediated transport process (Jmax = 1.83 +/- 0.56 pmol/s per cm proximal tubular
      length, Km = 1.37 +/- 0.57 mmol/l). Oxalate inhibited the sulphate transport in a
      dose-dependent manner (Ki = 2. 06 +/- 0.82 mmol/l). No significant differences
      were found between the Ki values and the Km values of the two substances,
      indicating that oxalate and sulphate are transported by the same carrier across
      the basolateral membrane of the proximal tubule. Oxalate transport was not
      dependent on the extracellular sodium or potassium concentration. Bicarbonate
      competitively inhibited the oxalate transport. Chloride significantly inhibited
      the oxalate transport, but not dose dependently. It is, therefore, suggested that
      oxalate is transported into the cell of the proximal tubule in exchange for
      sulphate or bicarbonate. The dose-independent inhibition by chloride is suggested
      to be mediated by the coupling of the sulphate (bicarbonate)/oxalate exchanger
      with the chloride/bicarbonate exchanger at the basolateral membrane of the
      proximal tubule. This, furthermore, suggests that the transport of oxalate or
      sulphate across the basolateral membrane might be indirectly coupled with the
      reabsorption of chloride at this membrane side.

PMID- 9518513
TI  - Dexamethasone's influence on tyrosine hydroxylase activity in the chemoreflex
      pathway and on the hypoxic ventilatory response.
AB  - Catecholamines have been implicated in neuromodulation of peripheral
      chemosensitivity and central respiratory mechanisms. Because glucocorticoids can
      affect catecholamine metabolism in the carotid body and brainstem, this study
      explored the possibility that, in rats, dexamethasone or adrenalectomy affects
      catecholamine biosynthesis in carotid body chemoreceptors and the medullary areas
      (A2C2, A5, A6, A7) involved in the chemoreflex pathway and the hypoxic
      ventilatory response (HVR). One dexamethasone injection (1 mg/kg body wt.)
      stimulated tyrosine hydroxylase activity in the carotid body and had no effect in
      brainstem catecholamine areas, while HVR was reduced. Chronic dexamethasone (1
      mg/kg body wt. daily for 10 days) had a stimulatory influence on tyrosine
      hydroxylase activity in the carotid body and an inhibitory effect on A2C2, A5 and
      A7 cell groups. Breathing pattern, but not HVR, was altered. Adrenalectomy
      elicited an increase in tyrosine hydroxylase activity in A2C2, which was
      accompanied by a decreased respiratory frequency in hypoxia. The data show that
      glucocorticoids have differential effects on catecholamine biosynthesis in
      peripheral and central structures involved in the chemoreflex pathway. Depending
      on the treatment, the neurochemical changes were accompanied by alterations of
      HVR or the breathing pattern, which are consistent with a neuromodulating
      influence of catecholamines on peripheral chemosensory inputs or the central
      respiratory network.

PMID- 9518515
TI  - Myogenin mRNA is elevated during rapid, slow, and maintenance phases of stretch
      induced hypertrophy in chicken slow-tonic muscle.
AB  - Biochemical changes that are associated with the growth phase of stretch-induced
      skeletal muscle hypertrophy are better understood than events that maintain the
      increased muscle mass. One purpose of this study was to determine whether changes
      that occur during the period of rapid muscle hypertrophy persist during periods
      when muscle growth plateaus or the rate of enlargement slows. Serum response
      factor (SRF), myogenin, MyoD, and actin mRNA expression patterns were examined.
      SRF protein interactions with serum response element-1 (SRE1) of the chicken
      skeletal alpha-actin gene were also characterized. Anterior latissimus dorsi
      (ALD) wet weight (132% and 122%) and total RNA concentration (29% and 19%)
      increased after 2 and 3 weeks of stretch overload, respectively. Myogenin mRNA
      per microgram RNA increased after 3 (775%), 6 (1073%), 14 (227%), and 21 days
      (133%) of stretch overload. At 6 days, myogenin mRNA levels were increased in the
      distal, middle and proximal regions of the ALD. Serum response factor (SRF) mRNA
      per microgram total RNA was not increased after 2 or 3 weeks of stretch overload.
      MyoD and skeletal alpha-actin mRNAs per microgram total RNA were also unchanged
      after 2 and 3 weeks of stretch. Gel mobility shift assays demonstrated that SRF
      bound to SRE1 from 14-day-stretched ALD nuclear extracts had an increased
      mobility compared to control, and this difference in mobility was maintained in
      nuclear extracts from ALD muscle whose mass was declining. These results indicate
      that the expression of myogenin mRNA and total RNA remains elevated during either
      slow or maintenance periods of stretch-induced increases in ALD mass, when SRF
      mRNA has returned to control levels. Additionally, stretch-induced alterations in
      SRF binding to SRE1, from the skeletal alpha-actin promoter, occur regardless of
      the rate of stretch-induced growth.

PMID- 9518516
TI  - Involvement of Ca2+-induced Ca2+ release in the biphasic Ca2+ response evoked by
      readdition of Ca2+ to the medium after UTP-induced store depletion in A431 cells.
AB  - We have recently shown that the Ca2+ response in endothelial cells evoked by
      readdition of Ca2+ to the medium after store depletion caused by a submaximal
      concentration of agonist can involve Ca2+ release from Ca2+ stores sensitive to
      both inositol 1,4, 5-trisphosphate and ryanodine. The present experiments were
      performed to determine whether this mechanism might also exist in other types of
      cell. For this purpose, we used the human carcinoma cell line A431, which has a
      varied resting [Ca2+]i. We found that the amplitude of the Ca2+ response evoked
      by Ca2+ readdition did not correlate with the amplitude of the preceding UTP
      evoked Ca2+ release, but did positively correlate with the initial [Ca2+]i. An
      inspection of the two patterns of response seen in this study (the large biphasic
      and small plateau-shaped Ca2+ responses) revealed that there is an accelerating
      rise in [Ca2+]i during the biphasic response. Application of ryanodine during the
      plateau-shaped Ca2+ response reversibly transformed it into the biphasic type.
      Unlike ryanodine, caffeine did not itself evoke Ca2+ release, but it caused a
      further [Ca2+]i rise when [Ca2+]i had already been elevated by thapsigargin.
      These data suggest that in A431 cells, as in endothelial cells, the readdition of
      Ca2+ after agonist-evoked store depletion can evoke Ca2+-induced Ca2+ release.
      This indicates that Ca2+ entry may be overestimated by this widely used protocol.

PMID- 9518517
TI  - Expression of beta subunit modulates surface potential sensing by calcium
      channels.
AB  - We have expressed the alpha 1 A calcium channel subunit alone, and in combination
      with different beta subunits, and investigated the effect of the external Ba2+
      concentration on the voltage dependence of activation. Increasing the external
      Ba2+ concentration from 2.5 to 40 mM induced in all cases a depolarising shift of
      the potential for half-activation. The magnitude of this shift however, was
      different depending on whether the alpha 1 A subunit was expressed alone or with
      a beta subunit. Consistently, calculated external surface-charge density and
      potential were larger when a beta subunit was expressed. These results suggest
      that expression of an auxiliary subunit can influence calcium channel gating by
      modifying the sensitivity of the voltage sensor to the membrane potential
      profile.

PMID- 9518518
TI  - Interleukin-10 expression is induced by increase of intracellular calcium levels
      in the monocytic cell line U937.
AB  - The regulation of interleukin-10 (IL-10) expression after treatment with a high,
      exponential, electric pulse was investigated in the monocytic cell line U937.
      Recently, we showed IL-10 protein production in the monocytic cell lines U937 and
      THP-1 after exposure to a single, high exponential electric pulse [Lehmann MH,
      Hoffken K, Berg H (1996) Bioelectrochem. Bioenerg. 41: 227-229]. In the present
      study, the specificity of this process was proven by semiquantitative reverse
      transcriptase polymerase chain reaction. It was found that the presence of
      calcium in the culture medium during the pulse is essential for IL-10 protein
      production. Only a small amount of IL-10 protein was produced in calcium free
      medium. The calcium specific chelator EGTA prevented IL-10 protein production
      induced by the electric pulse in a dose-dependent manner. Additionally, IL-10
      mRNA transcription could be induced in U937 cells without pulse application by
      means of the calcium ionophore ionomycin. No IL-10 protein could be detected by
      ELISA. However, down-regulation of TNF-alpha mRNA levels after ionomycin
      stimulation provided an indirect proof that IL-10 protein production occurred.

PMID- 9518519
TI  - Nervous network in larvae of the ascidian Ciona intestinalis.
AB  - With the use of the monoclonal antibody UA301, which specifically recognizes the
      nervous system in ascidian larvae, the neuronal connections of the peripheral and
      central nervous systems in the ascidian Ciona intestinalis were observed. Three
      types of peripheral nervous system neurons were found: two located in the larval
      trunk and the other in the larval tail. These neurons were epidermal and their
      axons extended to the central nervous system and connected with the visceral
      ganglion directly or indirectly. The most rostral system (rostral trunk epidermal
      neurons, RTEN) was distributed bilateral-symmetrically. In addition, presumptive
      papillar neurons in palps were found which might be related to the RTEN. Another
      neuron group (apical trunk epidermal neurons, ATEN) was located in the apical
      part of the trunk. The caudal peripheral nervous system (caudal epidermal
      neurons, CEN) was located at the dorsal and ventral midline of the caudal
      epidermis. In the larval central nervous system, two major axon bundles were
      observed: one was of a photoreceptor complex and the other was connected with
      RTEN. These axon bundles joined in the posterior sensory vesicle, ran posteriorly
      through the visceral ganglion and branched into two caudal nerves which ran along
      the lateral walls of the caudal nerve tube. In addition, some immunopositive
      cells existed in the most proximal part of the caudal nerve tube and may be
      motoneurons.

PMID- 9518520
TI  - Involvement of blood-group-B-active trisaccharides in Ca2+-dependent cell-cell
      adhesion in the Xenopus blastula.
AB  - Despite their wide distribution in various organisms, no physiological roles have
      been proposed for the human blood-group-ABO (ABH)-active trisaccharides. Here we
      show that monoclonal antibodies against human blood-group-B-active trisaccharides
      (B-substance) completely block the Ca2+-dependent cell-cell adhesion system of
      frog (Xenopus laevis) embryonic cells. Synthetic B-substance or B-active
      glycopeptides also disrupt the Ca2+ -dependent cell-cell adhesion. These results
      suggest that blood-group-B-active substances play a role in cell-cell adhesion.
      Blood-group-B-active substances were found as glycoproteins and as
      glycosphingolipids. In order to identify B-active glycoproteins active in cell
      cell adhesion, we purified B-active membrane glycoproteins by two-dimensional
      electrophoresis and found that they are 45- to 58-kDa proteins with pI(s) ranging
      from 4.0 to 5.3. They are glycosylphosphatidyl inositol (GPI) anchored. Amino
      acid sequence analysis showed that the purified B-active GPI-anchored proteins
      are homologues of soluble Xenopus cortical granule lectins (CGL). The results
      suggest that the B-active membrane glycoproteins are GPI-anchored forms of the
      lectin and are directly involved in frog Ca 2+-dependent cell-cell adhesion.

PMID- 9518522
TI  - Gangliogenesis in leech: morphogenetic processes leading to segmentation in the
      central nervous system.
AB  - Using intracellular lineage tracers to study the main neurogenic lineage (N
      lineage) of the glossiphoniid leech embryo, we have characterized events leading
      from continuous columns of segmental founder cells (nf and ns primary blast
      cells) to discrete, segmentally iterated ganglia. The separation between
      prospective ganglia was first evident as a fissure between the posterior boundary
      of nf- and the anterior boundary of ns-derived progeny. We also identified the
      sublineages of nf-derived cells that contribute parallel stripes of cells to each
      segment. These stripes of cells project ventrolaterally from the dorsolateral
      margin of each nascent ganglion to the ventral body wall. The position and
      orientation of the stripes suggests that they play a role in forming the
      posterior segmental nerve; they are not coincident with the ganglionic boundary,
      and they form well after the separation of ganglionic primordia. Previous work
      has shown that cells in the anterior stripe express the leech engrailed-class
      gene. Thus, in contrast to the role of cells expressing engrailed in Drosophila,
      the stripes of N-derived cells expressing an engrailed-class gene in leech do not
      seem to play a direct role in segmentation or segment polarity.

PMID- 9518521
TI  - The activity of Drosophila Hairless is required in pupae but not in embryos to
      inhibit Notch signal transduction.
AB  - Drosophila Hairless (H) encodes a negative regulator of Notch signalling. H
      activity antagonizes Notch (N) signalling during bristle development at the pupal
      stage. We show here by clonal analysis that H acts by inhibiting signal
      transduction rather than by promoting signal production, during both selection of
      microchaete precursors in the notum and vein cell differentiation in the wing.
      Allele-specific interactions further suggest that H inhibits Notch signal
      transduction by interacting directly with Suppressor of Hairless. Unexpectedly,
      this regulatory function of H appears to be essential only during imaginal
      development. Using a null allele of H that corresponds to a deletion of the H
      coding sequence, we show that embryos devoid of both maternal and zygotic gene
      products develop similarly to wild-type embryos. Thus, H activity is not strictly
      required to regulate N-mediated cell fate choices in the embryo.

PMID- 9518523
TI  - The wingless gene is required for embryonic brain development in Drosophila.
AB  - We have studied the role of the wingless gene in embryonic brain development of
      Drosophila. wingless is expressed in a large domain in the anlage of the
      protocerebrum and also transiently in smaller domains in the anlagen of the
      deutocerebrum and tritocerebrum. Elimination of the wingless gene in null mutants
      has dramatic effects on the developing protocerebrum; although initially
      generated, approximately one half of the protocerebrum is deleted in wingless
      null mutants by apoptotic cell death at late embryonic stages. Using temperature
      sensitive mutants, a rescue of the mutant phenotype can be achieved by stage
      specific expression of functional wingless protein during embryonic stages 9-10.
      This time period correlates with that of neuroblast specification but preceeds
      the generation and subsequent loss of protocerebral neurons. Ectopic wingless
      over-expression in gain-of-function mutants results in dramatically oversized
      CNS. We conclude that wingless is required for the development of the anterior
      protocerebral brain region in Drosophila. We propose that an important role of
      wingless in this part of the developing brain is the determination of neural cell
      fate.

PMID- 9518524
TI  - Cytological evidence of spontaneous androgenesis in the freshwater clam Corbicula
      leana Prime.
AB  - Cytological observations and DNA microfluorometry of the hermaphrodite freshwater
      triploid clam Corbicula leana revealed unusual androgenetic development as
      follows: (1) the maternal genome of zygotes was extruded as two polar bodies just
      after karyokinesis of the first meiosis, (2) only chromosomes derived from one
      male pronucleus constituted the metaphase of the first cleavage of zygotes, (3)
      DNA content of 7-day-old veliger larvae was identical to the somatic cells of the
      parent. This spontaneous androgenetic process in C. leana zygotes is the first
      case in the phylum Mollusca and may be related to the specialized mode of
      reproduction; i.e. hermaphroditism and self-fertilization.

PMID- 9518525
TI  - Lox6, a leech Dfd ortholog, is expressed in the central nervous system and in
      peripheral sensory structures.
AB  - Sequence analysis of a newly isolated Hirudo medicinalis cDNA containing an
      Antennapedia (Antp)-class homeobox suggests that the corresponding gene, Lox6, is
      an ortholog of the Drosophila Deformed (Dfd) gene. In situ hybridization of whole
      mounted preparations shows that the major sites of Lox6 expression during
      embryogenesis are the central nervous system (CNS) and the peripheral sensory
      system. Lox6 mRNA can be detected in a subset of neurons in each ganglion from
      the subesophageal ganglion (RG2) to the most posterior ganglion, with the highest
      level of expression seen in RG3. Peripherally, Lox6 is expressed principally in
      the primordia of the sensillae and in the eyes. This pattern of expression of
      Lox6 suggests that one of its functions may be to contribute to the
      diversification of neuronal phenotypes.

PMID- 9518526
TI  - The carp homeobox gene Ovx1 shows early expression during gastrulation and
      subsequently in the vagal lobe, the facial lobe and the ventral telencephalon.
AB  - The homeobox gene Carp-Ovx1 shows similarity to vertebrate and invertebrate Ovx
      genes and to Drosophila unplugged. Its expression pattern was studied by in situ
      hybridization in carp embryos and juveniles. During segmentation, expression
      becomes gradually limited to the neural tube. In juveniles up to 9 weeks old,
      cells in the ventral telencephalon, the facial lobe and the vagal lobe show Ovx1
      expression, confining expression to parts with chemosensory projections.

PMID- 9518527
TI  - Alteration of the neurofilament sidearm and its relation to neurofilament
      compaction occurring with traumatic axonal injury.
AB  - Traumatic injury evokes two characteristic forms of focal axonal injury, one of
      which involves focal perturbation of axolemmal permeability associated with rapid
      compaction of the underlying axonal neurofilament lattice and microtubular loss.
      In this process, the neurofilament sidearms have been the subject of intense
      scrutiny in relation to their role in this NF compaction, with the suggestion
      that the sidearms, thought to maintain interfilament distance, are
      proteolytically cleaved and degraded at the time of injury. The current
      communication addresses the fate of the NF sidearms in such injured axons. Adult
      cats were subjected to moderate/severe fluid percussion brain injury after
      intrathecal administration of horseradish peroxidase (HRP). This tracer, excluded
      by the intact axolemma of uninjured axons, was used to recognize injured axons
      via HRP intra-axonal uptake/flooding with HRP. Animals were perfused and
      processed for light microscopic and electron microscopic study of both HRP
      containing and non-HRP-containing axons from the same field. HRP-containing axons
      consistently displayed evidence of traumatically-induced (NF) cytoskeletal
      collapse. Electron micrographs of HRP-containing axons as well as uninjured, non
      HRP-containing axons from the same fields were videographically captured,
      digitized, enlarged and analysed for NF sidearm length and NF density. HRP
      containing axons were found to have increased NF density. Surprisingly, this
      increased NF density occurred despite the retention of the NF sidearms, which
      now, however, were reduced in height in comparison to the non-HRP-containing
      uninjured axons. These observations are not consistent with previously published
      reports suggesting that overt proteolytic degradation of sidearms was responsible
      for NF compaction. Based on our findings, we suggest that the NF compaction
      associated with traumatically-induced axolemmal permeability changes may have its
      genesis in more subtle sidearm modification, perhaps involving a change in
      phosphorylation state.

PMID- 9518528
TI  - Protein-water-ion interactions in a model of the pore domain of a potassium
      channel: a simulation study.
AB  - A model of the selectivity filter of a voltage-gated K+ (Kv) channel formed by an
      eight-stranded beta-barrel is compared with physiological properties of the
      channel. Continuum electrostatic calculations suggest that only two of the eight
      Asp sidechains at the extracellular mouth of the pore will ionise. A ring of four
      Tyr sidechains forms the narrowest region of the pore. Molecular dynamic
      simulations of the potential energy of a K+ ion as translated along the model
      pore indicate that the two ionised Asp sidechains and the hydroxyl groups of the
      Tyr sidechains stabilise the partially desolvated ion as it passes through the
      narrowest region.

PMID- 9518529
TI  - Fatty acid binding to rat liver fatty acid-binding protein is modulated by early
      glycolytic intermediates.
AB  - Fatty acid binding to rat liver fatty acid binding protein in the presence of
      glycolytic metabolites and at different pH (optimal 7.2) and ionic strength was
      studied. Binding decreased logarithmically with ionic strength. Glucose and
      glucose-6-phosphate increased fatty acid binding significantly with K0.5 within
      physiological ranges while glucose-1-phosphate and phosphate ion caused no
      effect.

PMID- 9518530
TI  - Regional localization of agmatine in the rat brain: an immunocytochemical study.
AB  - The distribution of agmatine (decarboxylated arginine) was mapped in the central
      nervous system (CNS) in the rat. Agmatine-like immunoreactivity was identified by
      light microscopy, exclusively in the cytoplasm of neuronal perikarya.
      Immunoreactive neurons were present in the cerebral cortex, predominantly within
      laminae VI and V and, to a lesser extent, III and mainly in retrosplenial,
      cingulate, primary somatosensory and auditory cortices, and the subiculum. In the
      lower brainstem, immunoreactivity was selectively localized to visceral relay
      nuclei: the nucleus tractus solitarii and pontine parabrachial complex, and
      periventricular areas including the laterodorsal nucleus, locus coeruleus and
      dorsal raphe. In the midbrain, immunolabeled cells were concentrated in the
      ventral tegmental area and periaqueductal gray. In the forebrain, subcortical
      neurons were labeled predominantly in the preoptic area, amygdala, septum, bed
      nucleus of the stria terminalis, midline thalamus, and the hypothalamus.
      Ultrastructural analysis of layer V of the somatosensory cortex demonstrated
      agmatine-immunoreactivity in neurons, primarily in large dense-core vesicles
      located in the cytoplasm. Agmatine immunoreactivity was also affiliated with
      endoplasmic reticulum and the plasmalemma. Cortical neurons and the subiculum
      were labeled in animals not administered the axonal transport inhibitor,
      colchicine; thus, may normally contain higher concentrations of the amine than
      other brain regions. The central distribution of agmatine is consistent with the
      hypothesis that the amine may be a novel neurotransmitter of neurons involved in
      behavioral and visceral control.

PMID- 9518532
TI  - Dopamine D2 receptor bands in normal human temporal cortex are absent in
      Alzheimer's disease.
AB  - A modular organization of bands enriched in high concentrations of D2 receptors
      are observed throughout the rostral to caudal aspects of the temporal cortex of
      the normal human at postmortem, but are most frequently observed in the inferior
      and superior temporal cortices [S. Goldsmith, J.N. Joyce, Dopamine D2 receptors
      are organized in bands in normal human temporal cortex, Neuroscience 74 (1996)
      435-451]. In the tissue derived at postmortem from Alzheimer's disease cases
      (AD), these D2 receptor-enriched modules were found to be largely absent at
      rostral and mid-levels of the temporal cortex. Regions exhibiting this loss of
      receptor binding also showed a marked reduction in the number of pyramidal
      neurons stained for D2 mRNA. In addition, the AD material exhibited numerous
      thioflavin-positive plaques and tangle-filled extraneuronal (ghost) pyramidal
      neurons that were D2 mRNA-negative. Regions that are the earliest affected and
      most susceptible to classical AD pathology are also most sensitive to the loss of
      D2 receptors. These results, along with our previous data [J.N. Joyce, C. Kaeger,
      H. Ryoo, S. Goldsmith, Dopamine D2 receptors in the hippocampus and amygdala in
      Alzheimer's disease, Neurosci. Lett. 154 (1993) 171-174; H. Ryoo, J. N. Joyce,
      The loss of dopamine D2 receptors varies along the rostrocaudal axis of the
      hippocampal complex in Alzheimer's disease, J. Comp. Neurol. 348 (1994) 94-110],
      indicate that specific pathways enriched with D2 receptors, including that within
      modules of higher order association cortices of the temporal lobe and continued
      through segregated pathways within the parahippocampus and hippocampus, are
      particularly susceptible to the loss in AD. These dopamine D2 receptor-enriched
      modules may play an important role in the reciprocal activity of large groups of
      neurons in these high-order association cortical regions. Hence, the loss of the
      D2 receptor-enriched modules in Alzheimer's disease contributes to disturbances
      in information processing in these high-order association cortices, and may
      promote the cognitive and non-cognitive impairments observed in Alzheimer's
      disease.

PMID- 9518531
TI  - cDNA cloning of a 8-lipoxygenase and a novel epidermis-type lipoxygenase from
      phorbol ester-treated mouse skin.
AB  - Using a combination of PCR cloning and conventional screening procedures, we
      isolated from phorbol ester-treated mouse epidermis two full length cDNA clones
      encoding novel lipoxygenases. One of the cDNAs turned out to be identical to the
      recently cloned 8-lipoxygenase [Jisaka et al., J. Biol. Chem. 272 (1997) 24 410
      24 416], the open reading frame of the second one corresponded to a protein of
      701 amino acids with a calculated molecular mass of 80.6 kDa. The amino acid
      sequence showed 50.8% identity to human 15-lipoxygenase 2, approximately 40% to 5
      lipoxygenase and 35% to 12- and 15-lipoxygenases. A unique structural feature is
      the insertion of 31 amino acid residues in the amino-terminal part of the
      molecule. Based on these data, we conclude that this epidermis-derived cDNA
      encodes a novel lipoxygenase isoform termed provisionally epidermis-type
      lipoxygenase 2 (e-LOX 2).

PMID- 9518533
TI  - Ion channels involved in insulin release are activated by osmotic swelling of
      pancreatic B-cells.
AB  - Measurements of the membrane potential showed that osmotic swelling (-80
      mosmol/l) of pancreatic B-cells led to a transient hyperpolarization followed by
      a more sustained depolarization of the cell membrane. Cell swelling triggers a
      transient activation of the K+ATP current and of an inward current, carried by Cl
      . This current was inhibited by DIDS, D600, and by omission of extracellular
      Ca2+. The depolarization opens voltage dependent L-type Ca2+ channels, thereby
      increasing the intracellular Ca2+ activity ([Ca2+]i). This effect was blunted by
      D600 or abolished by omission of Ca2+. Moreover, osmotic swelling transiently
      increased the amplitude of the Ca2+ currents. Replacement of NaCl by d-mannitol
      proved that the observed effects are due to an increase in cell volume and not to
      a reduction of extracellular Na+ or Cl-. Our results suggest that regulatory
      volume decrease is achieved by activation of K+ and Cl- currents. The Cl- current
      is responsible for the previously described depolarization and increase in
      insulin release induced by osmotic cell swelling.

PMID- 9518535
TI  - Advanced lipid peroxidation end-products in Alexander's disease.
AB  - Rosenthal fibers (RF), intra-astrocytic hyaline inclusions, accumulate in various
      pathological conditions and are the histological hallmark of Alexander's disease.
      While the major protein components of RF have been identified, the factors
      accounting for their pathogenesis, accumulation, and insolubility are largely
      unknown. In this study, we immunohistochemically examined three cases of
      Alexander's disease using antibodies to a lysine-derived pyrrole modification
      arising from 4-hydroxy-2-nonenal, a highly cytotoxic reactive aldehyde produced
      by lipid peroxidation. In all the cases of Alexander's disease examined, strong
      immunolabeling of RF by the antibodies to 4-hydroxy-2-nonenal pyrrole adducts
      were noted. By contrast, age-matched control cases showed no immunoreactivity.
      These results indicate that modification of protein by lipid peroxidation adducts
      may play an important role in the formation of RF as well as in the pathogenesis
      of Alexander's disease. Furthermore, taken together with our previous data
      indicating advanced Maillard reaction end products in RF, it seems that post
      translational modification of RF, initiated by oxidative stress, is critical for
      both the accumulation and the insolubility of RF, and therefore, by inference, in
      the pathogenesis of Alexander's disease.

PMID- 9518534
TI  - Lysophosphatidylcholine increases apolipoprotein B secretion by enhancing lipid
      synthesis and decreasing its intracellular degradation in HepG2 cells.
AB  - Free fatty acids and lysophosphatidylcholine (lysoPC) are the major lipids bound
      to human plasma albumin. The effects of fatty acids on the hepatic production of
      Apolipoprotein B (apo B) have been studied but those of lysoPC have not. In HepG2
      cells, lysoPC increased apo B secretion in different experiments by 50-120%, but
      did not affect the flotation properties of secreted lipoproteins. LysoPC affected
      neither the cellular protein levels nor apo A-I secretion suggesting that its
      effect was specific to apo B. Apo B secretion was maximum after incubating cells
      for 6 h with 0.2 mM lysoPC as equimolar fatty acid free bovine serum albumin
      (BSA) complexes. LysoPC was metabolized by cells and its fatty acids were used
      for the synthesis of phosphatidylcholine and triglycerides (TG). Experiments were
      performed to understand the mechanism of lysoPC action. LysoPC increased the
      incorporation of 3H-glycerol into newly synthesized cellular (3-fold) and
      secreted (4-fold) triglycerides, and increased the synthesis (40%) and secretion
      (4-fold) of phospholipids. LysoPC did not affect apo B synthesis, but inhibited
      the intracellular degradation of apo B and increased its secretion. Triacsin C (5
      microM), an inhibitor of long chain acyl-CoA synthase, completely inhibited the
      induction of lipid synthesis and abolished the effect of lysoPC on apo B
      secretion. These studies indicated that lysoPC increased apo B secretion by
      inducing lipid synthesis; newly synthesized lipids probably protected apo B from
      intracellular degradation and enhanced secretion. These studies are consistent
      with the hypothesis that physiologic concentrations of lysoPC can be an important
      modulator for hepatic apo B secretion.

PMID- 9518536
TI  - Probing DNA-cationic lipid interactions with the fluorophore trimethylammonium
      diphenyl-hexatriene (TMADPH).
AB  - The aim of this study is to get a better understanding of DNA-cationic lipid
      complex formation and its characterization through the properties of the lipid
      assembly, using fluorescent probes known to have different locations in the
      vesicle bilayer, 1,6-diphenylhexa-1,3,5-triene (DPH) and 1-(4
      trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene (TMADPH). The location of
      these two fluorescent probes in the membrane differs; the positive charge of
      TMADPH is localized close to the water/lipid interface and its fluorophore is
      present in the upper part of the acyl chain region while DPH (lacking polar
      group) is embedded deeper in the hydrophobic part of the bilayer. Unilamellar
      vesicles ( approximately 100 nm size) composed of N-(1-(2, 3-dioleoyloxy)-propyl)
      N,N,N-trimethylammonium chloride (DOTAP) and 1,2-dioleoyl-sn-glycero-3
      phosphoethanolamine (DOPE) as a helper lipid (at 1 : 1 mole ratio) were used as a
      model of cationic liposomes. Both linear and circular DNA gave almost identical
      results. DNA-/L+ (mole charge ratio of DNA negatively-charged phosphate to
      positively-charged lipid) ratios have large effects on the measured parameters.
      The effects monitored through TMADPH are much more striking than those obtained
      through the use of DPH, suggesting that the major DNA-lipid interaction occurs at
      the lipid/water interface. The fact that DNA induced much larger changes in
      TMADPH fluorescence intensity in H2O than in D2O suggests that the changes in the
      exposure of TMADPH to water and solvent relaxation effects are involved in the
      interaction. At DNA-/L+>/=1, fluorescence intensity increased concomitantly with
      a small increase in TMADPH fluorescence anisotropy without much affect in the
      size of the complex. At DNA-/L+<0.6, fluorescence quenching proportional to DNA
      /L+ occurred, as well as a large increase in TMADPH fluorescence anisotropy and
      in complex size. These results suggest that at low DNA-/L+, negatively-charged
      DNA condenses positively-charged lipid headgroups, thereby inducing formation of
      lipid-ordered domains. This phase separation results in membrane defects at the
      lipid/water interface and increased exposure of the hydrophobic upper parts of
      the acyl chains to water, as indicated by the quenching of TMADPH. This leads to
      instability and aggregation/fusion of the DNA-lipid complexes. On the other hand,
      at DNA-/L+>/=1, the condensing effect is smaller, involving homogeneous lateral
      condensation of all the lipids, leading to a reduction in water content near the
      probe, and the DNA-lipid complexes are relatively small and stable.

PMID- 9518537
TI  - Cerebro-protective effects of ENA713, a novel acetylcholinesterase inhibitor, in
      closed head injury in the rat.
AB  - Focal ischemic brain damage and diffuse brain swelling occur in severe cases of
      traumatic head injury. Ischemia decreases brain acetylcholine (ACh) levels and
      head trauma upregulates acetylcholinesterase (AChE) in experimental animal
      models. The present study determined whether a brain-selective AChE inhibitor,
      ENA713, given once, up to 2 h after closed head injury (CHI) could reduce the
      vasogenic edema and accelerate recovery from neurological deficits induced by the
      injury in rats. ENA713 1-5 mg/kg produced a dose-related inhibition of AChE
      ranging from 40-85% in the cortex and hippocampus. Doses of 1, 2 and 5 mg/kg,
      significantly reduced the motor and neurological deficits and speeded recovery,
      as indicated by measurements made 7 and 14 days after injury. The two larger
      doses were still effective when injected 1 or 2 h after CHI. The acceleration by
      ENA713 of recovery of motor function was independent of its reduction in body
      temperature and was prevented by the simultaneous injection of mecamylamine (2.5
      mg/kg), but not by scopolamine (0.2 or 1 mg/kg). Edema in the contused hemisphere
      (24 h after injury) and disruption of the blood brain barrier (4 h after injury)
      were significantly reduced (about 50%) by doses of 2 and 5 mg/kg, but not by 1
      mg/kg. The data support the hypothesis that ENA713 exerts a neuroprotective
      effect in brain injury by preventing the decrease in cholinergic activity in
      cerebral vessels and in neurones.

PMID- 9518538
TI  - GABA receptor-mediated post-synaptic potentials in the retrohippocampal cortices:
      regional, laminar and cellular comparisons.
AB  - Inhibitory post-synaptic potentials (IPSPs) were studied in neurons of
      presubiculum, parasubiculum and medial entorhinal cortex in horizontal slices
      from rat brains. Isolated IPSPs were evoked by extracellular electrical stimuli
      in the presence of glutamate receptor antagonists. Cellular morphology was
      identified using Neurobiotin labeling. IPSPs were compared: (a) across
      morphological cell types, (b) across laminae within regions, and (c) across
      regions. IPSPs were visible in stellate and pyramidal cells from layers II, III,
      and V of all retrohippocampal areas during bath application of glutamate
      antagonists. Qualitative and quantitative differences in IPSPs were only found
      when comparing responses by superficial layer II, III cells to responses by deep
      layer V cells. Responses by stellate and pyramidal cells within the same or
      adjacent layers did not differ, nor did responses differ from region to region.
      All cell types exhibited an early hyperpolarizing response. The majority (85%) of
      superficial layer cells in all regions, regardless of cell shape, exhibited a
      second hyperpolarizing component. Fewer (50%) deep layer cells exhibited the late
      peak with similar long latencies. IPSPs were typically larger in superficial
      layer cells. IPSPs were comprised of GABAA and GABAB (gamma-aminobutyric acid)
      receptor-mediated components. With repetitive stimulation, the peak amplitude of
      the GABAA receptor-mediated component decreased with successive stimuli, but
      stabilized during the first five or fewer stimuli to a level that did not vary
      with stimulation frequency. The GABAB receptor-mediated component also
      stabilized, but the final amplitude appeared to decrease as the stimulation
      frequency increased. With high-frequency repetitive stimulation, both components
      of the IPSP showed summation. We conclude that the most meaningful distinction
      for IPSPs among retrohippocampal neurons is a laminar distinction, between
      superficial and deep layer neurons, and not one across cell shape or
      retrohippocampal subregion. These laminar differences can contribute to
      synchronous activity by deep layer neurons and restrict the activity of
      superficial layer neurons.

PMID- 9518539
TI  - Trolox and 6,7-dinitroquinoxaline-2,3-dione prevent necrosis but not apoptosis in
      cultured neurons subjected to oxygen deprivation.
AB  - There is a growing body of evidence suggesting that apoptosis is involved in
      ischemic brain injury. Recent studies suggest that a rapid necrosis masked a more
      subtle apoptotic death in neurons subjected to oxygen deprivation in culture. To
      test this hypothesis, we treated cultured neurons with potential antinecrotic
      drugs during and after oxygen deprivation. The results show that 6, 7
      dinitroquinoxaline-2,3-dione (DNQX) and 6-hydroxy-2,5,7, 8-tetramethylchroman-2
      carboxylic acid (Trolox), which interfered with kainate receptor activation and
      lipid peroxidation respectively, prevented necrosis but allowed neurons to
      undergo apoptosis. Flow cytometric analysis of DNA degradation and hydrogen
      peroxide generation, as well as fluorescent microscopy of nuclear fragmentation
      revealed that apoptotic activity was higher in 6, 7-dinitroquinoxaline-2,3-dione
      treated cells than in Trolox-treated cells. This difference in occurrence of
      apoptosis may be due to the difference in oxidative stress generated from these
      two different agents.

PMID- 9518540
TI  - Acetyl-CoA carboxylase control of fatty acid oxidation in hearts from hibernating
      Richardson's ground squirrels.
AB  - Although mammalian hibernators rely on stored body fat as a source of energy,
      direct measurement of energy substrate preference in heart tissue during
      hibernation, as well as potential mechanisms controlling fatty acid oxidation has
      not been examined. In order to determine whether an increase in fatty acid
      utilization occurs during hibernation, glucose and palmitate oxidation were
      measured in isolated working hearts from hibernating and non-hibernating
      Richardson's ground Squirrels. Hearts were perfused at either 37 degrees or 5
      degrees C with perfusate containing 11 mM [U-14C]glucose and 1.2 mM [9,10
      3H]palmitate, which allowed for direct measurement of both glucose oxidation
      (14CO2 production) and fatty acid oxidation (3H2O production). The contribution
      of fatty acid oxidation as a source of citric acid cycle acetyl-CoA was
      significantly greater in hearts from hibernating animals, compared to hearts from
      non-hibernating animals. Since acetyl-CoA carboxylase (ACC) regulates cardiac
      fatty acid oxidation (producing malonyl-CoA, a potent inhibitor of mitochondrial
      fatty acid uptake), we measured the activity and expression of ACC in these
      hearts. ACC activity was significantly decreased in hibernating ground squirrels,
      regardless of whether ACC was assayed at 37 degrees or 5 degrees C. This decrease
      in activity could not be explained by a change in the activity of 5'AMP-activated
      protein kinase, which can phosphorylate and inhibit ACC. Rather, the expression
      of the 280 kDa isoform of ACC (which predominates in cardiac muscle) was
      decreased in hearts from hibernating squirrel hearts. This suggests that a down
      regulation of ACC expression occurs as an adaptation for the increased
      utilization of fatty acid in hearts of hibernating ground squirrels.

PMID- 9518541
TI  - Comparison of the interaction of doxorubicin, daunorubicin, idarubicin and
      idarubicinol with large unilamellar vesicles. Circular dichroism study.
AB  - Doxorubicin, daunorubicin and other anthracycline antibiotics constitute one of
      the most important groups of drugs used today in cancer chemotherapy. The details
      of the drug interactions with membranes are of particular importance in the
      understanding of their kinetics of passive diffusion through the membrane which
      is itself basic in the context of multidrug resistance (MDR) of cancer cells.
      Anthracyclines are amphiphilic molecules possessing dihydroxyanthraquinone ring
      system which is neutral under the physiological conditions. Their lipophilicity
      depends on the substituents. The amino sugar moiety bears the positive
      electrostatic charge localised at the protonated amino nitrogen. The four
      anthracyclines used in this study doxorubicin, daunorubicin, idarubicin and
      idarubicinol (an idarubicin metabolite readily formed inside the cells) have the
      same amino sugar moiety, daunosamine, with pKa of 8.4. Thus, all drugs studied
      will exhibit very similar electrostatic interactions with membranes, while the
      major differences in overall drug-membrane behaviour will result from their
      hydrophobic features. Circular dichroism (CD) spectroscopy was used to understand
      more precisely the conformational aspects of the drug-membrane systems. Large
      unilamellar vesicles (LUV) consisting of phosphatidylcholine, phosphatidic acid
      (PA) and cholesterol, were used. The anthracycline-LUV interactions depend on the
      molar ratio of phospholipids per drug. At low molar ratios drug:PA, these
      interactions depend also on the anthracycline lipophilicity. Thus, both
      doxorubicin and daunorubicin bind to membranes as monomers and their CD signal in
      the visible is positive. However, doxorubicin with its very low lipophilicity
      binds to the LUV through electrostatic interactions, with the
      dihydroxyanthraquinone moiety being in the aqueous phase, while daunorubicin,
      which is more lipophilic is unable to bind only through electrostatic
      interactions and actually the hydrophobic interactions are the only detected. The
      highly hydrophobic idarubicin, forms within the bilayer a rather complex entity
      involving 2-3 molecules of idarubicin associated in the right-handed
      conformation, one cholesterol molecule and also molecule(s) of phosphatidic acid,
      as this special oligomeric species is not detected in the absence of negatively
      charged phospholipids. Idarubicinol differs from idarubicin with CH(13)-OH
      instead of C(13)=O and its interactions with LUV are distinctly different. Its CD
      signal in the visible becomes negative and no self associations of the molecule
      within the bilayer could be detected. The variation of the sign of the Cotton
      effect (positive to negative) may derive from the changes in the C(6a)-C(7)-O(7)
      C(1') dihedral angle. It is noteworthy that C(13)-OH group, which strongly
      favours formation of the dimeric species in aqueous solutions when compared to
      idarubicin prevent association inside the LUV bilayer. At high ratios of
      phospholipids per drug all of them are embedded within the bilayer as monomer.

PMID- 9518542
TI  - Chronic treatment with lithium and pretreatment with excess inositol reduce
      inositol pool size in astrocytes by different mechanisms.
AB  - Chronic treatment with a lithium salt is the classical treatment for manic
      depressive disorder. It is hypothesized that the therapeutic action of lithium is
      caused by its inhibition of inositol phosphatases which leads to a relative
      deficiency of inositol and, therefore, an impairment of inositol recycling and
      production of precursor for the second messengers inositol triphosphate (IP3) and
      diacylglycerol (DAG). However, peculiarly enough, treatment with high doses of
      inositol also has an antidepressant effect. In the present work, we have studied
      the acute and chronic effects of lithium and of excess inositol, in separation or
      together, on accumulation of 50 microM [3H]inositol (a physiologically relevant
      concentration) into primary cultures of mouse astrocytes. Two parameters were
      investigated: (1) rate of unidirectional uptake across the cell membrane
      (measured during short-term exposure to the radioisotope), and (2) magnitude of
      the intracellular pool of inositol, equilibrating with extracellular inositol
      (measured during long-term exposure to the radioisotope). Inositol uptake was
      highly concentrative and occurred with a Km of approximately 500 microM and a
      Vmax of 1.5 nmol/min/mg protein. The uptake rate was not affected by either acute
      or chronic treatment with LiCl (or both), but it was substantially reduced ('down
      regulated') after pretreatment with a high concentration of inositol. The
      inositol pool size was decreased to a similar extent as the uptake rate by
      previous exposure to excess inositol. In spite of the fact that inositol uptake
      rate was unaffected by lithium, the magnitude of the inositol pool was
      significantly decreased by chronic treatment with a pharmacologically relevant
      concentration of LiCl (1 mM), but not by treatment with lower concentrations.
      This decrease is likely to reflect a reduction in either inositol synthesis or
      replenishment of inositol from IP3, due to the inhibition of inositol
      phosphatases by the lithium ion. In agreement with the different mechanisms by
      which lithium and pretreatment with excess inositol appear to reduce the pool
      size of inositol, the effects of pretreatment with excess inositol and of LiCl
      were additive. It is noteworthy that both effects could be observed in
      astrocytes, suggesting that there might be a significant astrocytic target during
      clinical treatment.

PMID- 9518543
TI  - Production of the Fos protein after contextual fear conditioning of C57BL/6N
      mice.
AB  - Male C57BL/6N mice were chosen to determine Fos production during acquisition of
      context-dependent fear and after re-exposure to the conditioning context. Fear
      conditioning was induced by a single exposure of mice to a context followed by an
      electric shock. Control groups consisted of mice exposed to context only (Context
      group) or to an immediate electric shock. When contextual retention was measured
      24 h after conditioning (retention test 1), significant contextual generalization
      was observed. However, when animals were exposed to a different context from days
      2-5 after conditioning and then tested for retention on day 6 (retention test 2),
      generalization was markedly reduced. After the training, the fear-conditioned
      mice produced higher Fos levels than mice exposed to an immediate shock in the
      hippocampus, medial amygdaloid nucleus and parietal somatosensory cortex. Both
      shock groups produced significantly more Fos than the Context group in the
      central nucleus of the amygdala. After retention test 1, fear-conditioned mice
      generated more Fos in the hippocampus and central amygdaloid nucleus than the two
      control groups. However, all groups exhibited similarly low Fos production after
      retention test 2. The results demonstrated that simultaneous Fos production in
      the hippocampus, central and medial nuclei of amygdala and somatosensory parietal
      cortex closely paralleled the ability of mice to acquire conditioned fear. In
      contrast, Fos production after the retention tests did not correlate with the
      expression of conditioned fear.

PMID- 9518544
TI  - Regulation of prostaglandin H2 synthase-2 expression in primary human amnion
      cells by tyrosine kinase dependent mechanisms.
AB  - Prostaglandin H2 synthase (PGHS)-1 and PGHS-2 expression was examined in primary
      cultures of human amnion cells, an in vitro model of amnion tissue. Epidermal
      growth factor (EGF), the protein kinase C (PKC) activating phorbol ester TPA, and
      the protein phosphatase inhibitor, okadaic acid (OA), stimulated PGHS activity
      and the level of PGHS-2 mRNA, but did not affect the level of PGHS-1 mRNA. In
      situ hybridization suggested that the same population of cells responded to EGF,
      TPA and OA. Okadaic acid promoted PGHS activity independently of PKC. EGF
      stimulated the activity of extracellular signal-regulated protein kinase (Erk)
      and N-terminal c-Jun kinase (Jnk). OA increased Jnk activity but had no effect on
      Erk activity, while TPA had no influence on either Erk or Jnk activity. PD098059,
      a selective inhibitor of the Erk-activating kinase MEK, blocked the stimulation
      of PGHS expression by EGF, but did not decrease stimulation in response to OA.
      Herbimycin A, a tyrosine kinase inhibitor, suppressed the stimulation of PGHS
      activity and PGHS-2 mRNA abundance by all three stimulants, and blocked
      signalling via the Erk and Jnk mitogen-activated protein kinase pathways. Thus,
      growth factor stimulation, PKC activation and protein phosphatase inhibition
      induced the expression of PGHS-2 in primary amnion cells by distinct regulatory
      mechanisms involving tyrosine kinase(s). Tyrosine kinase inhibitors may
      constitute a new category of PGHS-2 inhibitors that act by blocking the
      expression of the enzyme.

PMID- 9518545
TI  - Growth-associated protein-43 (GAP-43) in the regenerating periodontal Ruffini
      endings of the rat incisor following injury to the inferior alveolar nerve.
AB  - Alterations in the levels of growth-associated protein 43 (GAP-43)-like
      immunoreactivity (-LI) were examined in the lingual periodontal ligament of the
      rat incisor following two types of injury (resection and crush) to the inferior
      alveolar nerve (IAN). In normal animals, GAP-43-like immunoreactive (IR)
      structures were observed as tree-like ramifications in the alveolar half of the
      lingual periodontal ligament of incisors. Under immunoelectron microscopy, GAP-43
      LI appeared in the Schwann sheaths associated with periodontal Ruffini endings;
      neither cell bodies of the terminal Schwann cells nor axonal profiles showed GAP
      43-LI. During regeneration of the periodontal Ruffini endings following resection
      of the IAN, GAP-43-LI appeared in the cytoplasm of the terminal Schwann cell
      bodies and axoplasm of the terminals. The distribution of GAP-43-LI in the
      Ruffini endings returned to almost normal levels on days 28 and 56 following the
      injury. The changes in the distribution of GAP-43-LI following the crush injury
      were similar to those following resection; however, expression of GAP-43-LI was
      slightly higher for the entire experimental period compared with the resection.
      The transient expression of GAP-43 in the terminal Schwann cells and axonal
      profiles of the periodontal Ruffini endings following nerve injury suggests that
      GAP-43 is closely associated with axon-Schwann cells interactions during
      regeneration.

PMID- 9518547
TI  - Intracerebroventricular prostaglandin administration increases the neural damage
      evoked by global hemispheric hypoxic ischemia.
AB  - This study was designed to determine if central (intracerebroventricular, i.c.v.)
      administration of prostaglandin E2 (PGE2, mediator of core temperature elevation
      following exogenous or endogenous pyrogen administration) worsens the neural
      damage of anesthetized rats to global hemispheric hypoxic-ischemia (GHHI) from
      damage seen in normothermic, i.c.v. saline control groups. The first study (no
      GHHI) showed that 10 or 50 ng PGE2 given i.c.v. to groups of anesthetized Long
      Evans rats evoked dose-related increases in colonic (systemic core) temperature
      but no neural damage. In the second study anesthetized rats were given an i.c.v.
      injection of sterile saline or PGE2 plus GHHI (ligation of the right common
      carotid artery plus 35 min of 12% O2) at the peak of the temperature response.
      Thermal response indices (TRI, degrees C x min), determined from brain
      (temporalis muscle, ipsilateral and contralateral to ligation) and core (colonic)
      temperatures, showed significant increases in the 50-ng PGE2 group compared to
      the TRIs of the 10-ng PGE2 or saline control group. The 50-ng PGE2, GHHI group
      had a higher mortality rate and showed greater ipsilateral hemispheric neural
      damage than the saline-treated group given the same insult, especially due to
      increased damage to the cortex. The results show that i.c.v. PGE2 administration
      significantly increases the neural damage caused by GHHI, possibly due to the
      associated rise in core temperature.

PMID- 9518546
TI  - Relative magnitudes of the rate constants associated with monensin-mediated H+,
      Na+ and K+ translocations across phospholipid vesicular membranes.
AB  - Monensin (Mon)-mediated decay of the pH difference (DeltapH) across soyabean
      phospholipid vesicular membrane has been studied as a function of K+ and Na+ ion
      concentrations. In these experiments, the DeltapH was created using temperature
      jump, and ionic strength was regulated at 0.3 using CsCl. Rate constants
      associated with the translocation of Mon-H, Mon-K and Mon-Na have been estimated
      (without making any assumptions) from an analysis of the DeltapH decay data.
      These estimates contradict the claim made in the literature (E. Nachliel, Y.
      Finkelstein, M. Gutman, Biochim. Biophys. Acta, 1285 (1996) 131-145) that the
      translocation rate constants of the three above-mentioned species are
      significantly different. Our observations on the changes in DeltapH decay rate on
      adding carbonyl cyanide m-chlorophenylhydrazone (CCCP) also suggest that the
      dominant barrier to the DeltapH decay process is not the 'polar region' of the
      membrane. Therefore, the differences in the electric dipole moments of Mon-H, Mon
      K and Mon-Na are unlikely to cause large differences in their translocation rate
      constants.

PMID- 9518548
TI  - Sympathetic neurite outgrowth is greater on plaque-poor vs. plaque-rich regions
      of Alzheimer's disease cryostat sections.
AB  - Senile plaques are a characteristic histopathological feature of Alzheimer's
      disease (AD) and are associated with altered neuritic morphology. Numerous
      individual plaque components, most notably beta-amyloid, have been studied for
      their possible effects on neurite outgrowth in culture. However, the effect of
      senile plaques on neuronal morphology and function is difficult to assess. In the
      present study, the effect of senile plaques on neurite outgrowth was studied by
      culturing embryonic chick sympathetic neuronal explants on Alzheimer's tissue
      sections. Explants were cultured for 3 days on amygdala tissue sections from AD
      as well as non-AD patients in serum-free medium. Neurite outgrowth on plaque-rich
      regions was compared with outgrowth on plaque-poor regions of the same tissue
      section, and with outgrowth on non-AD tissue, through colocalization of the
      living explants and the underlying plaques. Explants growing on plaque-rich
      regions showed significantly less neurite outgrowth compared with those on plaque
      poor regions in the same section or on control brain tissue. These results
      suggest that plaques are poor substrates for neurite outgrowth as compared with
      non-plaque areas of the same tissue sections, and support the hypothesis that
      components of the senile plaques may inhibit neurite outgrowth.

PMID- 9518549
TI  - Characterization of Mg2+ transport in brush border membrane vesicles of rabbit
      ileum studied with mag-fura-2.
AB  - Mg2+ transport in rabbit ileal brush border membrane vesicles (BBMV) was
      characterized by means of a modified mag-fura-2 technique. In the presence of an
      i>o Na+ gradient, BBMV showed a saturable Mg2+ uptake with a Km of 1.64 mmol l-1.
      There was no evidence of an overshoot. K+, Li+, and choline+ were as effective as
      Na+ in stimulating Mg2+ transport. In contrast, only a small amount of Mg2+
      transport was observed in the presence either of an o>i Na+ gradient, or in an
      Na+ equilibrium or in the absence of Na+. Moreover, the findings that Na+ efflux
      was not stimulated but inhibited by outside Mg2+ and that the nonfluorescent
      amiloride-analogues DMA and EIPA did not affect Mg2+ transport do not favour the
      idea of an Mg2+/Na+ antiport system. At Cl- equilibrium, independent of the Na+
      gradient, the rate of Mg2+ transport was markedly suppressed compared with the
      transport rate noted in the presence of an i>o Cl- gradient. The stimulating
      effect of inside anions could be enhanced by SCN- and decreased by SO2-4.
      Furthermore, nonfluorescent anion transport antagonist H2-DIDS stimulated Mg2+
      transport. These findings indicate that Mg2+ transport can be modulated by inside
      anions. Mg2+ transport appeared to be electroneutral because it was not dependent
      on membrane potential. Mg2+ transport was neither stimulated by Bay K8644, a Ca2+
      channel agonist, nor inhibited by verapamil, diltiazem, nifedipine and
      imipramine, the Ca2+ channel antagonists. It, therefore, seems unlikely that Mg2+
      uses the Ca2+ transport system.

PMID- 9518550
TI  - Two distinct phosphatidylinositol-specific phospholipase Cs from Streptomyces
      antibioticus.
AB  - Two phosphatidylinositol-specific phospholipase C (PI-PLC) genes from
      Streptomyces antibioticus were cloned by a shotgun method using Streptomyces
      lividans TK24 as a host. The genes of the two PI-PLCs (named as PLC1 and PLC2)
      were adjoined and opposite in the direction of transcription/translation. Both of
      them were confirmed to be expressed in S. antibioticus. The two enzymes were
      different in the following properties. (i) PLC2 had considerable sequence
      similarity to other bacterial PI-PLCs, while PLC1 had a short stretch that was
      similar to PI-PLCs of eukaryotes rather than the other bacterial enzymes. (ii)
      PLC1 was Ca2+-dependent, whereas PLC2 was not. (iii) PLC1 generated myo-inositol
      1-phosphate and myo-inositol-1:2-cyclic phosphate simultaneously from PI, but
      PLC2 showed sequential formation of them. (iv) PLC2 has GPI-anchor-degrading
      activity while PLC1 does not have. Both enzymes did not hydrolyze
      phosphatidylcholine, phosphatidylinositol-4-monophosphate and
      phosphatidylinositol-4,5-bisphosphate. Both PLC1 and PLC2 contained two histidine
      residues that might be catalytic residues. PLC1 has residues that possibly form a
      Ca2+-binding site. Then it was suggested that both PLC1 and PLC2 act according to
      the catalytic mechanism using the two histidine residues as proposed in both
      eukaryotic and prokaryotic enzymes, but that PLC1 has a more 'eukaryotic'
      mechanism in which Ca2+ participates than that of the Ca2+-independent bacterial
      enzymes. Thus, we propose that PLC2 is a conventional 'bacteria-type' enzyme,
      while PLC1 is more closely related to the eukaryotic enzymes rather than the
      bacterial enzymes.

PMID- 9518551
TI  - Agonist-induced desensitization of adenylyl cyclase activity mediated by 5
      hydroxytryptamine7 receptors in rat frontocortical astrocytes.
AB  - Our previous study has demonstrated that astrocytes derived from the rat frontal
      cortex contain 5-hydroxytryptamine (5-HT)7 receptors positively coupled to
      adenylyl cyclase. In this study, we observed a desensitization of 5-HT7 receptors
      induced by a treatment with agonists (0.1, 1, and 10 muM, 0.5 to 3.5 h). Maximum
      responses, but not the EC50 values, in the concentration-response curve of 5-HT
      induced cyclic AMP formation were decreased after pretreatment with 5-HT.
      Pretreatment with 5-carboxamidotryptamine (5-CT) elicited a potent
      desensitization of 5-HT-induced cyclic AMP formation. Neither 2-methyl-5-HT nor
      alpha-methyl-5-HT caused the desensitization. When the astrocytes were treated
      with isoproterenol, N-ethylcarboxamidoadenosine, and dibutyryl cyclic AMP (all of
      which increase intracellular cyclic AMP levels), 5-HT-induced cyclic AMP
      responses were not affected. Conversely, adenylyl cyclase activity mediated by
      either isoproterenol or N-ethylcarboxamidoadenosine was attenuated by
      pretreatment with each of these agonists, but not 5-HT. In addition, our study
      showed that the administration of 5-HT, 5-CT, and 8-hydroxy-2-(di-n
      propylamino)tetralin to the astrocytes stimulated cyclic AMP formation both in
      the presence and absence of forskolin, whereas in neuron-rich cultures of the
      frontal cortex, these agonists did not change basal cyclic AMP levels and
      decreased forskolin-stimulated cyclic AMP formation. Neurons may predominantly
      contain 5-HT1A receptors that are negatively coupled to adenylyl cyclase. These
      results suggest that 5-HT7 receptors are highly expressed in astrocytes but not
      in neuronal cells, and that pretreatment with their agonists results in a
      homologous desensitization of the receptors.

PMID- 9518552
TI  - Intracerebroventricular norepinephrine potentiation of the perforant path-evoked
      potential in dentate gyrus of anesthetized and awake rats: A role for both alpha-
      and beta-adrenoceptor activation.
AB  - Norepinephrine (NE) applied iontophoretically to the dentate gyrus in vivo, and
      bath applied to hippocampal slices in vitro, produces potentiation of the
      perforant path-evoked potential. beta-receptors mediate exogenous NE potentiation
      in vitro, while alpha-receptors are implicated in exogenous effects in vivo. The
      present study uses intracerebroventricular (i.c.v.) NE to mimic in vitro bath
      conditions in vivo. Short-term NE potentiation was reliably seen with 10 microg
      [+/-] NE in 2 microl of 0.9% saline i.c.v. Long-term potentiation occurred with
      higher doses of NE. The beta-agonist isoproterenol and the alpha-agonist
      phenylephrine also produced potentiation. Long-term effects were common with
      isoproterenol. The beta-antagonist metoprolol and the alpha-antagonist
      phentolamine attenuated NE potentiation. The results suggest that both alpha- and
      beta-receptors could play a role in NE potentiation in dentate gyrus in vivo. In
      awake animals, 10 microg NE i.c.v. reproduced the potentiation pattern seen in
      anesthetized rats. NE potentiation in awake rats was independent of behavioral
      variation.

PMID- 9518553
TI  - The effects of strychnine, bicuculline, and ketamine on 'immersion-inhibited'
      dorsal horn convergent neurons in intact and spinalized rats.
AB  - In both intact and spinalized rats, this study examined the effects of strychnine
      (a glycine antagonist), bicuculline (a GABAA antagonist), and ketamine (a non
      competitive NMDA receptor antagonist) on one particular class of lumbar dorsal
      horn convergent neurons. This group of convergent neurons are inhibited when a
      rat's entire ipsilateral hindpaw is immersed in 50 degrees C water and has a
      strong afterdischarge as soon as the paw is removed from the water. Strychnine (2
      mg/kg, iv) increased ongoing activity and blocked the 'inhibition phase' in both
      intact and spinalized rats demonstrating that a spinal-related glycine mechanism
      was involved in the inhibition. However, only in intact rats did the firing rate
      of the 'afterdischarge phase' increase significantly from pre-drug levels,
      suggesting that supraspinal sites may be involved in modulating this phase.
      Ketamine (15 mg/kg, iv) depressed ongoing activity and the firing rate in the
      afterdischarge phase of these neurons. Additionally, ketamine reversed the
      strychnine-induced increase in ongoing activity. Bicuculline (2 mg/kg, iv) had no
      effect on the activity of this cell class. As shown previously, and replicated
      here, these 'immersion-inhibited' neurons invariably have both inhibitory and
      excitatory mechano-receptive fields on the ipsilateral hindpaw. Thus, the
      response of this class of convergent neurons to noxious stimulation may be a
      function of relative inputs of glycine and EAA's, each possibly triggered by the
      stimulation of different receptive fields/regions on the same paw. Furthermore,
      when both fields are co-stimulated during noxious immersion of the entire paw,
      glycine has a stronger influence on activity than does the EAA's.

PMID- 9518554
TI  - Phase structures of binary lipid bilayers as revealed by permeability of small
      molecules.
AB  - The effects of changes in bilayer phase structure on the permeability of acetic
      acid and trimethylacetic acid were studied in large unilamellar vesicles (LUVs)
      composed of dipalmitoylphosphatidylcholine (DPPC)/cholesterol (CHOL),
      dihexadecylphosphatidylcholine (DHPC)/CHOL, or
      DPPC/dimyristoylphosphatidylcholine (DMPC) using an NMR line-broadening method.
      Phase transitions were induced by changes in temperature and lipid composition
      (i.e., XCHOL was varied from 0.0 to 0.5 and XDMPC from 0.0 to 1.0). In DPPC/CHOL
      and DHPC/CHOL bilayers, the addition of CHOL induces only a modest change in the
      permeability coefficient (Pm) of acetic acid in the gel-phase (Pbeta') but
      significantly reduces Pm in ordered and disordered liquid-crystalline phases (Lo
      and Lalpha). Abrupt changes in slopes in semi-logarithmic plots of Pm vs. XCHOL
      occur at specific values of XCHOL and temperature corresponding to the boundaries
      between Pbeta' and Lo or between Lalpha and Lo phases. In most respects, phase
      diagrams generated from the break points in plots of Pm vs. XCHOL obtained at
      various temperatures in DHPC/CHOL and DPPC/CHOL bilayers closely resemble those
      constructed previously for DPPC/CHOL bilayers using NMR and DSC methods. Above
      Tm, the phase diagrams generated from permeability data reveal the presence of
      both the disordered (Lalpha) and the ordered (Lo) liquid-crystalline phases, as
      well as the two-phase coexistence region. In DPPC/DMPC bilayers, the addition of
      DMPC increases Pm dramatically in the gel phase but only slightly in the liquid
      crystalline phase. Abrupt changes in slopes in semi-logarithmic plots of Pm vs.
      XDMPC also occur at specific values of XDMPC and temperature, from which a phase
      diagram can be constructed which closely resembles diagrams obtained previously
      by other methods. These correlations indicate that trans-bilayer permeability
      measurements can be used to construct lipid bilayer phase diagrams. Positive
      deviations of Pm from predicted values based on the phase lever rule are observed
      in the two-phase coexistence regions with the degree of the deviation depending
      on bilayer chemical composition and temperature. These results may reflect a
      specific contribution of the interfacial region between two phases to higher
      solute permeability or may be due to the higher lateral compressibility of lipid
      bilayers in the two-phase coexistence region.

PMID- 9518555
TI  - Conformation of apolipoprotein AI in reconstituted lipoprotein particles and
      particle-membrane interaction: effect of cholesterol.
AB  - Discoidal recombinant high density lipoproteins (rHDL) of apolipoprotein AI
      (apoAI) and palmitoyloleoylphosphatidylcholine (POPC), with or without
      cholesterol, were prepared by cholate dialysis. By gel filtration, rHDL
      containing 2-4 (Lp2, Lp3 and Lp4) apoAI molecules/particle were obtained. The
      ApoAI conformation in these rHDL was investigated by tryptophan fluorescence,
      denaturation with guanidine HCl, and immunoreactivity with two monoclonal
      antibodies recognizing epitopes in the N-terminal and central domains. Data show
      that apoAI conformation is highly dependent on particle size as well as on
      cholesterol. The ability of rHDL to interact with lipid bilayer was studied by
      measuring leakage induction on POPC and POPC/cholesterol vesicles loaded with
      terbium/dipicolinic acid. Among the cholesterol-free rHDL, the most efficient
      ones were the smallest Lp2. Leakage induction on POPC vesicles is dramatically
      decreased by the presence of cholesterol in Lp2 and Lp3. All the rHDL, but
      specially those containing cholesterol, induced more leakage on the
      POPC/cholesterol than on the POPC vesicles. These results suggest that in small
      cholesterol-poor particles, apoAI could have a conformation determining a high
      affinity for membranes, which could facilitate cholesterol efflux. After
      cholesterol enrichment, a conformational change in apoAI could decrease the
      affinity for membranes allowing the lipoprotein release.

PMID- 9518556
TI  - Effect of allopurinol on NMDA receptor modification following recurrent asphyxia
      in newborn piglets.
AB  - The present study tests the hypothesis that repeated episodes of asphyxia will
      lead to alterations in the characteristics of the N-methyl-d-aspartate (NMDA)
      receptor in the brain cell membrane of newborn piglets and that pre-treatment
      with allopurinol, a xanthine oxidase inhibitor, will prevent these modifications.
      Eighteen newborn piglets were studied. Six untreated and six allopurinol treated
      animals were subjected to eight asphyxial episodes and compared to six normoxic,
      normocapneic controls. Brain cell membrane Na+,K+-ATPase activity was determined
      to assess membrane function. Na+,K+-ATPase activity was decreased from control
      following asphyxia in both the untreated and treated animals (47.7+/-3.2 vs.
      43.0+/-2.2 and 41.0+/-5.3 micromol Pi/mg protein/h, p<0.05, respectively). 3H-MK
      801 binding studies were performed to measure NMDA receptor binding
      characteristics. The receptor density (Bmax) in the untreated asphyxia group was
      decreased compared to control animals (0.80+/-0.11 vs. 1.13+/-0.33, p<0.05);
      furthermore, the dissociation constant (Kd) was also decreased (3.8+/-0.7 vs.
      9.2+/-2.2, p<0.05), indicating an increase in receptor affinity. In contrast,
      Bmax in the allopurinol treated asphyxia group was similar to control (1. 06+/
      0.37); and Kd was higher (lower affinity) than in the untreated group (6.5+/-1.4,
      p<0.05). The data indicate that recurrent asphyxial episodes lead to alterations
      in NMDA receptor characteristics; and that despite cell membrane dysfunction as
      seen by a decrease in Na+,K+-ATPase activity, allopurinol prevents modification
      of NMDA receptor-ion channel binding characteristics induced by repeated episodes
      of asphyxia.

PMID- 9518558
TI  - Topological study of Vibrio alginolyticus NhaB Na+/H+ antiporter using gene
      fusions in Escherichia coli cells.
AB  - NhaB, an Na+/H+ antiporter, of Vibrio alginolyticus is a 528-amino-acid protein.
      Hydropathy profile-based computer analysis predicted that the NhaB might contain
      up to 13 membrane-spanning domains. To examine this hypothesis, we applied the
      phoA fusion method to the cloned nhaB gene. Eighteen plasmid-borne nhaB-phoA
      fusion genes were constructed in Escherichia coli cells and the alkaline
      phosphatase activity and expression level of the fusion proteins analyzed. These
      results and the results obtained with additional constructs indicated that V.
      alginolyticus NhaB has a unique topology consisting of nine transmembrane
      segments with the N-terminus in the cytoplasm and the C-terminus in the
      periplasm.

PMID- 9518557
TI  - Analysis of c-Fos and glial fibrillary acidic protein (GFAP) expression following
      topical application of potassium chloride (KCl) to the brain surface.
AB  - Application of high K+ concentrations to a limited area of the brain surface is
      known to trigger spreading depression. We used this model to observe the response
      of cortical areas, distant to the exposed site, at the cellular level.
      Immunostaining of glial fibrillary acidic protein (GFAP) and of the proto
      oncogene c-Fos was analyzed in brain sections at different times after K+
      application. Piriform and parietal cortices, as observed in coronal sections
      located 3 mm rostrally from the center of the stimulated area and ipsilateral to
      it, showed a dramatic increase in immunostaining for both markers. However, the
      time course for such increments was different. c-Fos protein(s) expression was
      high at 1.5 h and decreased at 24 h after K+ exposure and c-fos mRNA expression
      correlated with the immunohistochemical results. At these initial times GFAP
      immunoreactivity was still low but began to rise between 2 and 7 days after
      treatment in exactly the same areas where c-Fos expression had been up-regulated.
      No significant effect, for either marker, was evident in the contralateral
      piriform or parietal cortices. In addition, we studied the effects of the NMDA
      antagonist MK-801 (4 mg/kg i.p.) on the expression of mRNA for GFAP and c-fos and
      demonstrated a marked reduction in the upregulation of these genes.

PMID- 9518559
TI  - In vivo studies with low doses of levocabastine and diphenhydramine, but not
      pyrilamine, antagonize neurotensin-mediated antinociception.
AB  - The present study describes in vivo experiments in the rat addressing the role of
      levocabastine, and two other specific histamine H1 antagonists, diphenhydramine
      and pyrilamine, at neurotensin (NT)-mediated hypothermia and antinociception
      (hotplate). Levocabastine given i.p. or microinjected directly into the
      periaqueductal gray (PAG) did not cause antinociception or hypothermia. This
      indicates that despite the results with the recently-cloned levocabastine
      sensitive NT receptors (NTR) in the rat (NTR-2) and mouse (NTRL), levocabastine
      by itself does not mediate either hypothermia or antinociception at NT receptors.
      However, pretreatment with 5 or 50 microg/kg of levocabastine or 5 microg/kg
      diphenhydramine all caused over a three-fold reduction in NT-mediated
      antinociception. Higher doses (500 or 5000 microg/kg) of levocabastine did not
      cause any antagonism of NT-mediated antinociception. All three antihistamines did
      not affect NT-mediated hypothermia. In addition, histamine H1 pathways are not
      involved in NT-mediated antinociception, as pretreatment with the much more
      potent histamine H1 antagonist pyrilamine did not affect antinociception mediated
      by NT. Therefore, these data may suggest the presence of yet unidentified NTR
      subtypes responsible for NT-mediated hypothermia and antinociception.

PMID- 9518560
TI  - A novel sulfonic-acid analogue of ceramide is the major extractable lipid of the
      gram-negative marine bacterium Cyclobacterium marinus WH.
AB  - The extractable lipids of the gram-negative, sea-water bacterium Cyclobacterium
      marinus strain WH contain about 94% of polar components which consist of two
      phospholipids, phosphatidylethanolamine (29% of the total lipids) and
      phosphatidylcholine (7%), and two phosphorus-free lipids. One of the latter has
      been shown to be a novel sulfonic-acid analogue of ceramide, 2-D-(2'-D-hydroxy
      13'-methyltetradecanoyl) amino-3-D-hydroxy-15-methylhexadec-4 (E)-en-1-sulfonic
      acid (48%), and other is a lipodipeptide, N-[3-d-(13'-methyltetradecanoyloxy)-15
      methylhexadecanoyl] glycyl-L-serine (11%), which has so far been found only in a
      Flavobacterium sp. strain. The dominant fatty acid residues of the phospholipids
      are iso-15:0, n-16:0, 16:1 and 18:1, the acyl residues linked to the sn-1 carbon
      of the glycerol moiety being somewhat more saturated as compared with those
      located at the sn-2 position. A new procedure for determination of the absolute
      configuration of 2- and 3-hydroxy fatty acids is briefly described.

PMID- 9518561
TI  - Role of glutathione in protection against noise-induced hearing loss.
AB  - A potential mechanism of hearing loss due to acoustic overstimulation is the
      generation of reactive oxygen species (ROS). ROS not removed by antioxidant
      defenses could be expected to cause significant damage to the sensory cells of
      the cochlea. We studied the influence of the antioxidant glutathione (GSH) on
      noise-induced hearing loss by using l-buthionine-[S,R]-sulfoximine (BSO), an
      inhibitor of GSH synthesis, and 2-oxothiazolidine-4-carboxylate (OTC), a cysteine
      prodrug, which promotes rapid restoration of GSH when GSH is acutely depleted.
      Pigmented female guinea pigs were exposed to broadband noise (102 dB SPL, 3
      h/day, 5 days) while receiving daily injections of BSO, OTC, or saline. By weeks
      2 and 3 after noise exposure, BSO-treated animals showed significantly greater
      threshold shifts above 12 kHz than saline-treated subjects, whereas OTC-treated
      animals showed significantly smaller threshold shifts at 12 kHz than controls.
      Histologically assessed noise-induced damage to the organ of Corti, predominantly
      basal turn row 1 outer hair cells, was most pronounced in BSO-treated animals.
      High performance liquid chromatographic analysis showed that OTC significantly
      increased cysteine levels, but not GSH levels, in the cochlea. These findings
      show that GSH inhibition increases the susceptibility of the cochlea to noise
      induced damage and that replenishing GSH, presumably by enhancing availability of
      cysteine, attenuates noise-induced cochlear damage.

PMID- 9518562
TI  - Genetic selection of mouse lines differing in sensitivity to a benzodiazepine
      receptor inverse agonist.
AB  - Mice were selectively bred according to their sensitivity or their resistance to
      the convulsive effects of a 4-mg/kg dose of methyl beta-carboline-3-carboxylate
      (beta-CCM), a benzodiazepine (BZ) receptor inverse agonist. The selection proved
      to be easy, with a clear separation of the two lines, convulsing with short
      latencies or resistant, already at the first generation of selection. Selection
      of a third line of animals convulsing with long latencies did not succeed. 3H-Ro
      15-1788 binding analysis provided evidence for a strong decrease in Bmax in the
      resistant line.

PMID- 9518563
TI  - Interactions of arbutin with dry and hydrated bilayers.
AB  - The glycosylated hydroquinone arbutin (4-hydroxyphenyl-beta-D-glucopyranoside) is
      abundant in certain resurrection plants, which can survive almost complete
      dehydration for prolonged periods. Little is known about the role of arbutin in
      vivo, but it is thought to contribute toward survival of the plants in the dry
      state. We have investigated the interactions of arbutin with model membranes
      under conditions of high and low hydration, as well as the possible participation
      of arbutin in carbohydrate glasses formed at low water contents. Retention of a
      trapped soluble marker inside large unilamellar vesicles and fusion of vesicles
      was monitored by fluorescence spectroscopy. Effects of arbutin on glass
      transition temperatures and hydrated membrane phase-transition temperatures were
      measured by differential scanning calorimetry. The possible insertion of arbutin
      into membrane bilayers was estimated by following arbutin auto-fluorescence.
      Evidence is presented that arbutin does not change the glass-transition
      temperature of a sucrose/trehalose glass, but that arbutin does interact with
      hydrated membranes by insertion of the phenol moiety into the lipid bilayer. This
      interaction causes increased membrane leakage during air-drying by a mechanism
      other than vesicle-vesicle fusion. Implications of these effects on the
      dehydrated plant cells, as well as possible methods of obviating the damage, are
      discussed.

PMID- 9518564
TI  - Attenuation of Fos expression to airpuff startle stimuli following tympanic
      membrane rupture.
AB  - The airpuff startle stimulus consists of two modalities, tactile and acoustic.
      Tympanic membrane rupture (TMR) effectively deafens a rat, thus preventing it
      from perceiving the acoustic component of the airpuff and permitting study of the
      tactile component in isolation. Previous studies have shown that the tactile
      modality is sufficient to drive the cardiovascular response to the airpuff, but
      cannot elicit the full behavioral startle response. In the present study Fos
      protein was used as a marker of neuronal activation to identify brain regions
      activated by the airpuff in both intact and TMR rats. Results show an attenuation
      of Fos expression following TMR in the dorsal and ventral cochlear nuclei,
      ventral nucleus of the lateral lemniscus and medial geniculate nucleus. In
      contrast, Fos expression following TMR was unchanged in the locus coeruleus, the
      laterodorsal tegmental nucleus, the supramammilary nucleus, and the ventromedial
      hypothalamic nucleus. Analysis of behavioral data confirmed that the startle
      response to the airpuff was diminished following TMR. These data are the first of
      which we know to employ an immediate early gene approach to discriminate between
      brain regions activated by the tactile and acoustic startle stimulus modalities.
      The results are discussed in terms of the classical acoustic startle circuit, and
      the central autonomic pathways activated by the tactile component of the airpuff.

PMID- 9518566
TI  - Modulation of cell signalling by ceramides.

PMID- 9518565
TI  - Effects of intracerebroventricular dizocilpine (MK801) on dehydration-induced
      dipsogenic responses, plasma vasopressin and c-fos expression in the rat
      forebrain.
AB  - This study determines the interaction between glutamate receptors and dehydration
      induced drinking, vasopressin (AVP) release, plasma osmolality and c-fos
      expression in the brain of conscious rats. The NMDA receptor antagonist
      dizocilpine (100 nmol infused into the cerebral ventricles) suppressed drinking
      following either 22 h water deprivation or intragastric injection of hypertonic
      saline (1.5 M), attenuated the increased plasma vasopressin induced by
      dehydration, but had no effects on peripheral hyperosmolality caused by either
      water deprivation or injections of hypertonic saline. Dizocilpine had no
      inhibitory effects on feeding after 24 h food deprivation. Dizocilpine also
      suppressed c-fos expression induced by dehydration in the median preoptic nucleus
      (MPN), the supraoptic and paraventricular nuclei (SON and PVN), but did not
      influence c-fos expression in the subfornical organ (SFO). The non-NMDA receptor
      antagonists CNQX (400 nmol) or DNQX (60 nmol) affected neither the animals'
      drinking nor c-fos expression induced by dehydration. Double staining showed that
      suppression of c-fos expression following dizocilpine occurred in the NMDA R1
      receptor containing neurons in the hypothalamus. These results suggest that the
      NMDA-type glutamate receptors may be involved in dehydration induced dipsogenic
      and neuroendocrinological responses. They complement our earlier findings that
      dizocilpine also attenuates drinking and c-fos expression following
      intraventricular infusions of angiotensin II.

PMID- 9518568
TI  - Effects of RPR 100893, a potent NK1 antagonist, on the jaw-opening reflex in the
      guinea pig.
AB  - RPR 100893 appears as a new potent NK1 selective non-peptide antagonist both in
      vitro and in vivo, and exhibits high affinity for guinea pig and human NK1
      receptor [M. Tabart, J.-F. Peyronel, Synthesis of RPR 100893, prototype of a new
      series of potent and selective non-peptide NK1 antagonists: the
      triarylperhydroisoindolols, Bioorg. Med. Chem. Lett., 4 (1994) 673-676.]. Intra
      oral administration of RPR 100893 (3, 15, 10, 30 mg/kg) was performed in freely
      moving guinea pigs during recording of the short- (6-10 ms) and long-latency (18
      26 ms) jaw-opening reflex (JOR) elicited by electrical stimulation (0.5 Hz) of
      the lower incisor tooth pulp. RPR 100893 induced a noticeable and dose-dependent
      increase of the long-latency reflex thresholds (P<0. 001) but was ineffective on
      the short-latency responses (P=0.14). The results suggest that, in guinea pigs,
      the long-latency JOR requires activation of NK1 receptors, while the earlier
      reflex component, elicited by activation of periodontal afferents, does not.
      These NK1 receptors could be located either on JOR interneurons activated by
      tooth pulp afferents or on digastric motoneurons, receiving the tooth pulp input
      through a polysynaptic pathway.

PMID- 9518569
TI  - The patterns of retinal ganglion cell death in hypertensive eyes.
AB  - We have recently described a rat model of hypertensive eye in which cauterizing
      limbal derived episcleral veins leads to increase in the intraocular pressure
      [S.R. Shareef, E. Garcia-Valenzuela, A. Salierno, J. Walsh, S.C. Sharma, Chronic
      ocular hypertension following episcleral venous occlusion in rats, Exp. Eye Res.
      61 (1995) 379-382.]. We have further documented that retinal ganglion cell death
      is apoptotic [E. Garcia-Valenzuela, S. Shareef, J. Walsh, S.C. Sharma, Programmed
      cell death of retinal ganglion cells during experimental glaucoma, Exp. Eye Res.
      61 (1995) 33-44.]. Here, we describe the total loss of retinal ganglion cells at
      various time intervals following increased IOP. At early time points death of
      ganglion cells in the central, peripheral retina occurred with similar
      frequencies. Between 4-6 weeks after intraocular elevation, ganglion cells in the
      peripheral retina were more susceptible than the central retina. Percentage of
      total ganglion cell death over the 10 week period was presumably linear and was
      about 4% per week.

PMID- 9518567
TI  - The substrate recognition domain in the Na+/dicarboxylate and Na+/sulfate
      cotransporters is located in the carboxy-terminal portion of the protein.
AB  - The Na+/dicarboxylate cotransporter, NaDC-1, and the Na+/sulfate cotransporter,
      NaSi-1, share 43% sequence identity, but they exhibit no overlap in substrate
      specificity. A functional chimera, SiDC-4, was prepared from NaDC-1 and NaSi-1 by
      homologous recombination and expressed in Xenopus oocytes. SiDC-4 contains
      putative transmembrane domains 1-4 of NaSi-1 (amino acids 1-139) and putative
      transmembrane domains 5-11 of NaDC-1 (amino acids 141-593). SiDC-4 retains the
      substrate specificity of NaDC-1, which suggests that the substrate recognition
      domain is found in the carboxy-terminal portion of the protein, past amino acid
      141. However, residues that affect substrate affinity and inhibition by
      furosemide and flufenamate are found in the amino terminal third of the protein.
      The cation binding properties of SiDC-4, including a stimulation of transport by
      lithium, differed from both parental transporters, suggesting that cation binding
      is determined by interactions between the amino- and carboxy-terminal portions of
      the protein. We conclude that the substrate recognition site of NaDC-1 and NaSi-1
      is found in the carboxy-terminal portion of the protein, past amino acid 141, but
      residues in the amino terminus can affect substrate affinity, inhibitor
      sensitivity, and cation selectivity.

PMID- 9518570
TI  - The dopamine D-1 receptor antagonist SCH 23390 injected into the dorsolateral bed
      nucleus of the stria terminalis decreased cocaine reinforcement in the rat.
AB  - The effects of bilateral intracranial injections of the D-1 dopamine receptor
      antagonist SCH 23390 HCl (0, 0.8, 1.6, 3.2, and 6.4 microgram total bilateral
      dose) administered into the dorsolateral bed nucleus of the stria terminalis
      (dlBNST) immediately prior to a 3 h intravenous cocaine self-administration
      session were examined. In addition, anatomical control injections of the most
      effective dose of SCH 23390 HCl (6.4 micogram) were made either 1.5 mm dorsal to
      the dlBNST or into the lateral ventricle. Injections directly into the dlBNST,
      but not those dorsal to the dlBNST or into the lateral ventricle, significantly
      increased the rate of cocaine self-administration within the first 20 min of the
      self-administration session, consistent with a partial attenuation of the
      reinforcing effects of cocaine under a fixed-ratio schedule of reinforcement
      (0.25 mg cocaine iv; fixed-ratio 5, timeout 20 s). Injections into all three
      sites increased cocaine self-administration across the entire 3 h session. These
      results suggest a role for D-1 dopamine receptors in the dlBNST in the
      reinforcing properties of self-administered cocaine, and also support the
      hypothesis that D-1 dopamine receptors in the 'extended amygdala' may play a
      significant role in cocaine self-administration.

PMID- 9518571
TI  - Bromothymol blue as a probe for structural changes of model membranes induced by
      hemoglobin.
AB  - The effect of methemoglobin on the structure of model membranes composed of
      phosphatidylcholine and diphosphatidylglycerol (18 : 1, mol : mol) was studied
      with the help of pH-indicator dye bromothymol blue. The partition coefficients
      characterizing the dye binding to methemoglobin or model membranes were derived
      from the pKaalpha dependences on the protein or phospholipid concentration. The
      observed character of the dye partitioning in the lipid or lipid-protein systems
      is interpreted in terms of the traditional electrostatic approach and some modern
      theories of membrane electrostatics. It is assumed that methemoglobin affects the
      structural and physicochemical parameters of lipid-water interface.

PMID- 9518573
TI  - Cytoskeletal regulation of the signal transduction of prostaglandin EP4 receptor.
AB  - Prostaglandin (PG) EP4 receptor is coupled to Gs, stimulating adenylate cyclase.
      We tested whether cytoskeleton modulates the signal transduction of the EP4
      receptor. A microtubule depolymerizing agent, colcemid, enhanced the PGE2-induced
      cAMP formation in the cloned EP4 receptor-expressing Chinese hamster ovary cells,
      but enhanced neither NaF plus AlCl3 nor forskolin-induced cAMP formation. Other
      microtubule depolymerizing agents, including colchicine, also induced the
      enhancement. These effects stemmed from the action of the agents on microtubules,
      because beta-lumicolchicine, an inactive isomer of colchicine, had no effect. In
      contrast, the microfilament depolymerizing agents did not affect the PGE2-induced
      cAMP formation but potentiated the enhancing effect of colcemid. This enhancement
      by colcemid was not due to the suppression of the desensitization of the EP4
      receptor. The enhancing effect of colcemid was also observed in another Gs
      coupled PGE receptor subtype, EP2 receptor. These results demonstrate that the
      state of microtubule assembly modulates the signal transduction of the EP4
      receptor in concert with microfilament.

PMID- 9518572
TI  - Hypoxia/reoxygenation induces apoptosis through biphasic induction of protein
      synthesis in cultured rat brain neurons.
AB  - To investigate biochemical events accounting for the outcome of central neurons
      following hypoxia/reoxygenation, cultured neurons from fetal rat forebrain were
      exposed to hypoxia (95% N2/5% CO2) for 6 h, and then reoxygenated for up to 96 h.
      Time-dependent changes in macromolecular biosynthesis were analysed by
      incorporation of [3H]uridine and [3H]leucine and were coupled to cell viability
      and lactate dehydrogenase leakage. Morphological features of necrosis and
      apoptosis were scored following nuclear incorporation of the fluorescent dye 4,6
      diamidino-2-phenylindole. Hypoxia led to a 36% reduction of cell viability at the
      end of the reoxygenation period, while 23% of the neurons exhibited apoptosis. A
      biphasic increase in the rates of protein synthesis was measured 1 h after the
      onset of hypoxia (77% above controls) and by 48-h postreoxygenation (72%). The
      presence of cycloheximide during hypoxia inhibited both peaks of synthesis and
      prevented the development of apoptosis. Protein electrophoresis outlined specific
      alterations in constitutive proteins, and immunohistochemistry revealed an
      overexpression of the pro-apoptotic gene products Bax and ICE. Therefore, hypoxia
      followed by reoxygenation would trigger sequential changes in synthesis of
      specific proteins, leading to delayed and mainly apoptotic neuronal death.

PMID- 9518575
TI  - Nitric oxide mediates brain mitochondrial damage during perinatal anoxia.
AB  - The possible role of nitric oxide (.NO) in brain energy metabolism during
      perinatal asphyxia in the rat was studied. Exposure of early neonates to 5 min of
      anoxia significantly inhibited brain mitochondrial complex II-III activity by
      25%, without affecting complex I, complex IV or citrate synthase activities. This
      insult was accompanied by ATP depletion (54%) and increased concentration of
      nitrites plus nitrates (1.4-fold), suggesting enhanced .NO synthesis.
      Administration of Nomega-nitro-L-arginine monomethyl ester (L-NAME) to the
      mothers inhibited neonatal brain .NO synthase activity, as reflected by the
      decreased (23%) cyclic GMP concentration. These L-NAME-treated neonates showed
      complete resistance to anoxic-mediated brain mitochondrial complex II-III damage.
      Our results suggest that brain mitochondrial dysfunction leading to energy
      deficiency during perinatal asphyxia is a .NO-mediated process.

PMID- 9518574
TI  - Locus coeruleus modulates thalamic nociceptive responses via adrenoceptors.
AB  - This study investigated the parafascicular (PF) neuronal nociceptive responses
      and their modulation following electrical stimulation of the locus coeruleus (LC)
      and intrathecal (i.t.) or intracerebroventricular (i.c.v.) administration of two
      alpha-adrenoceptor antagonists, the alpha2-antagonist, yohimbine, and the alpha1
      antagonist, prazosin. The main results were as follows: (1) the nociceptive
      evoked discharges in PF neurons were suppressed by preceding stimulation of LC;
      (2) the suppressive effect of LC stimulation on PF neurons was replaced by a
      facilitatory effect following pretreatment of i.t. yohimbine in 14 units tested,
      while i.t. prazosin failed to alter the LC-induced suppression, even when the
      prazosin dose was doubled; (3) i.c.v. pretreatment with prazosin strengthened the
      suppressive effect of LC stimulation on PF neurons; (4) i.c.v. norepinephrine
      (NE) administration induced, in PF neurons, a biphasic response to noxious
      stimulation; an early, brief (about 10 min) inhibitory effect followed by a late,
      long-lasting facilitatory effect; and (5) i.c.v. pretreatment of yohimbine or
      prazosin prevented the inhibitory or facilitatory responses released by NE,
      respectively. These results provide evidence that: (1) the LC-descending
      projections exhibit a suppressive effect on nociceptive transmission at the
      spinal level through alpha2-receptors; and (2) the LC-ascending projections
      exhibit dual effects, facilitatory and inhibitory, at the medial thalamus (PF)
      level through alpha1- and alpha2-receptors, respectively.

PMID- 9518576
TI  - Fe2+-induced inhibition of gerbil forebrain microsomal Ca2+-ATPase: effect of
      stobadine, glutathione and combination of both antioxidants.
AB  - The incubation of the gerbil forebrain microsomes in the presence of ferrous
      sulphate and EDTA for either 30 min or for 60 min at a temperature of 37 degrees
      C led to the inhibition of Ca2+-ATPase in both a concentration- and time
      dependent manner. The concentrations of Fe2+ which led to the inhibition of 50%
      of the Ca2+-ATPase activity (IC50-value) at these times were 0.59 mM and 0.07 mM,
      respectively. The preincubation of microsomes with 0.1 mM of stobadine prevented
      the inhibition of Ca2+-ATPase, however, the effectivity of prevention was
      dependent on the Fe2+ concentration. The net effect of stobadine was an increase
      in IC50-value to 0.76 mM. Unlike stobadine, reduced glutathione is a naturally
      occurring water soluble antioxidant. Glutathione at the concentration of 0.1 mM
      had no significant protective effect on the inhibition of Ca2+-ATPase. The
      protective effect of a stobadine-glutathione mixture was also investigated; 0.1
      mM of stobadine in combination with 0.1 mM of glutathione was more potent in
      prevention of Fe2+-induced inhibition of Ca2+-ATPase than stobadine alone
      (IC50=1. 31 mM). In addition, we have investigated the effect of various
      stobadine-glutathione molar ratios (the total concentration of both antioxidants
      being 0.2 mM) on Fe2+-induced inhibition of Ca2+-ATPase. The results indicated
      that the best stobadine-glutathione ratio was close to 1 : 1. The effect of 0.04
      mM stobadine in combination with 0.16 mM glutathione was comparable to the effect
      of 0.2 mM of stobadine alone, whereas 0.2 mM glutathione was almost ineffective.
      These results may suggest a possible role of membrane in Fe2+-induced inhibition
      of Ca2+-ATPase.

PMID- 9518577
TI  - Inhibition by soman of NMDA-stimulated [3H]norepinephrine release from rat
      cortical slices, studies of non-cholinergic effect.
AB  - Effects of soman, an irreversible cholinesterase (ChE) inhibitor, on
      [3H]norepinephrine (NE) release evoked by N-methyl-d-aspartate (NMDA) were
      studied in rat brain cortical slices. Soman inhibited NMDA-stimulated [3H]NE
      release in a concentration-dependent manner. This effect was neither reversed by
      atropine, an antagonist of the muscarinic receptor, nor by d-tubocurarine, an
      antagonist of the nicotinic receptor. Incubation of the slices with NMDA
      antagonists, AP5, MK-801, ketamine or magnesium, resulted in inhibitory effects
      on NMDA-stimulated [3H]NE release. Soman significantly shifted the inhibition
      curves downward and significant interactions between these chemicals and soman
      were observed. Glycine potentiated the release of [3H]NE stimulated by NMDA, and
      soman did not alter this effect of glycine. Soman also inhibited the release of
      [3H]NE evoked by K+ in a concentration-dependent manner. NMDA-stimulated [3H]NE
      release was inhibited by tetrodotoxin (TTX), an antagonist of voltage-dependent
      sodium channels, and a significant interaction between soman and TTX was
      observed. The [3H]NE release induced by NMDA was dependent on extracellular
      calcium concentrations and was inhibited by nifedipine, a selective blocker of
      the L-type voltage-dependent calcium channels (VDCC), or cadmium, a non-specific
      blocker of VDCC. However, no significant interaction between the effects of soman
      and calcium, nifedipine, or cadmium was observed. Taken together, the results
      suggested that: (1) soman has a direct action at non-cholinergic sites; (2) soman
      may interfere with some of the regulatory sites of the NMDA receptor-ion channel
      complex; and (3) the voltage-dependent sodium channel, but not VDCC, may be a
      site of action for soman.

PMID- 9518578
TI  - Light and electron microscopic evidence for topographic and monosynaptic
      projections from neurons in the ventral medulla to noradrenergic dendrites in the
      rat locus coeruleus.
AB  - Physiological studies have shown that afferents from the nucleus
      paragigantocellularis (PGi) in the rostral ventral medulla underlie the
      modulation of locus coeruleus (LC) activity by a variety of stimuli. However,
      there have been no anatomical demonstrations of a monosynaptic projection from
      neurons in the PGi to the LC. Thus, biotinylated dextran amine (BDA) was
      iontophoretically injected into the ventral medulla and single-tissue sections
      were processed for peroxidase localization of BDA and gold-silver labeling of
      tyrosine hydroxylase (TH). Discrete microinjections of BDA were placed into
      either the medial or lateral aspects of the ventral medulla. For medially placed
      injections, a medio-dorsal pathway to the LC was observed. This trajectory
      resulted in a predominant innervation of the ventral LC. Lateral injection
      placements yielded a fiber pathway that coursed more laterally within the medullo
      pontine reticular formation and primarily innervated the dorsolateral LC. These
      light microscopic data suggested that neurons in the PGi use distinct pathways to
      innervate the LC and are topographically organized within this structure.
      Electron microscopic analyses of the LC region indicated that axon terminals
      originating from either subregion were equally likely to contact noradrenergic
      neurons in the LC. Approximately 57% and 62% of BDA-labeled terminals originating
      from the medial (n=150) or lateral (n=150) aspects of the ventral medulla,
      respectively, formed heterogeneous synaptic contacts (i.e., inhibitory- and
      excitatory-type) with dendrites containing TH. It is well known that the PGi is a
      functionally diverse region that is involved in sensory integration, autonomic
      regulation and pain modulation. It is also known that LC efferents are spatially
      organized with respect to their postsynaptic targets. Taken together, our
      findings that subdivisions of the ventral medulla topographically and
      monosynaptically innervate the LC suggest that regionally specific PGi neurons
      target subsets of LC neurons with efferent targets that may possess analogous
      functional correlates.

PMID- 9518579
TI  - Surface behavior of myelin monolayers.
AB  - Myelin can be spread as a stable monomolecular layer, with reproducible
      properties, at the air-water interface. The major lipids and proteins of myelin
      are represented in this monolayer in molar ratios similar to those in the
      original membrane. A well-defined collapse point of the myelin monolayer occurs
      at ca. 46 mN/m. At a surface pressure of ca. 20 mN/m, the surface pressure
      molecular area isotherm of the myelin monolayer shows a change in its
      compressibility, exhibited as a diffuse but reproducible inflection with a
      clearly marked change of the surface compressional modulus; the surface potential
      area curve shows a change of slope at the same surface pressure. The myelin
      monolayer shows considerable hysteresis during the first compression
      decompression cycle; no detectable protein unfolding under expansion; and
      decreased hysteresis after the first cycle. The average molecular areas, the
      inflection at 20 mN/m, the variation of the surface potential per unit of
      molecular surface density, and the hysteresis properties of the myelin monolayer
      indicate that this membrane undergoes changes of intermolecular organization
      mostly ascribed to the protein fraction, above a lateral surface pressure of ca.
      20 mN/m. The behavior is consistent with a surface pressure-dependent relocation
      of protein components in the film. This has marked effects on the stability,
      molecular packing, and dipolar organization of the myelin interface.

PMID- 9518580
TI  - Crocin antagonizes ethanol inhibition of NMDA receptor-mediated responses in rat
      hippocampal neurons.
AB  - We have previously found that crocin (crocetin di-gentiobiose ester) antagonizes
      the inhibitory effect of ethanol on long-term potentiation in the rat hippocampus
      in vivo and in vitro. To explore mechanisms underlying the antagonism of crocin
      against ethanol, we investigated the effects of ethanol and crocin on synaptic
      potentials mediated by N-methyl-d-aspartate (NMDA) receptors in the dentate gyrus
      of rat hippocampal slices. Synaptic potential mediated by non-NMDA receptors was
      recorded in normal medium (1.3 mM Mg2+), while NMDA receptor-mediated synaptic
      potential was isolated in low (0.13 mM) Mg2+ medium containing the non-NMDA
      receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (10 microM). Crocin (10
      microM) alone did not affect synaptic potentials mediated by non-NMDA nor NMDA
      receptors. Non-NMDA response was slightly inhibited by 100 mM ethanol, while NMDA
      response was selectively inhibited by lower concentrations (10-50 mM) of ethanol.
      Crocin (10 microM) did not affect the inhibition of non-NMDA response by 100 mM
      ethanol, but significantly blocked the inhibition of NMDA response by 10-50 mM
      ethanol. In addition, we performed whole-cell patch recording with primary
      cultured rat hippocampal neurons, and confirmed that crocin blocked ethanol
      inhibition of inward currents evoked by application of NMDA. These results
      suggest that crocin specifically antagonizes the inhibitory effect of ethanol on
      NMDA receptor-mediated responses in hippocampal neurons.

PMID- 9518582
TI  - Method of purification affects some interfacial properties of pulmonary
      surfactant proteins B and C and their mixtures with
      dipalmitoylphosphatidylcholine.
AB  - Two methods were employed for preparation of lipid extracts from porcine lung
      surfactant. Pulmonary surfactant proteins SP-B and SP-C were isolated from the
      extracts using gel-exclusion chromatography on LH-60 with chloroform:methanol
      acidified with hydrochloric acid. Monolayers of pure SP-B or SP-C isolated from
      butanol lipid extracts spread at the air-water interface showed larger molecular
      areas than those determined in films of SP-B or SP-C isolated from chloroform
      surfactant extracts. Aqueous dispersions of dipalmitoylphosphatidylcholine (DPPC)
      supplemented with 2.5 and 5.0 wt% of SP-B or SP-C obtained from butanol extracts
      adsorbed faster to the air-water interface than their counterparts reconstituted
      with proteins isolated from chloroform extracts. Surface pressure-area
      characteristics of spread monolayers of DPPC plus SP-B or SP-C did not depend on
      the method of isolation of the proteins. The diagrams of the mean molecular areas
      vs. composition for the monolayers of DPPC plus SP-B or SP-C showed positive
      deviations from the additivity rule, independently of the procedure used for
      preparation of lipid extract surfactant. Matrix-assisted laser
      desorption/ionization spectrometry of the proteins isolated from different
      extraction solvents was consistent with some differences in the chemical
      compositions of SP-Bs. Butylation of SP-B during extraction of surfactant pellet
      with butanol may account for the differences observed in the molecular masses of
      SP-Bs isolated by the two different extraction protocols. The study suggests that
      the method of purification of SP-B and SP-C may modify their ability to enhance
      the adsorption rates of DPPC/protein mixtures, and this may be relevant to the
      formulation of protein-supplemented lipids for exogenous treatment of pulmonary
      surfactant insufficiency.

PMID- 9518581
TI  - Microinjection of GABA-A agonist muscimol into the dorsal but not the ventral
      hippocampus impairs non-mnemonic measures of delayed non-matching-to-position
      performance in rats.
AB  - Anatomical studies of afferent and efferent connections suggest that the
      hippocampus may have more than one information processing role that varies along
      the septo-hippocampal axis. The present study was conducted to test whether a
      distinct functional specialization for the dorsal versus ventral extents of the
      hippocampus could be detected. The effects of a GABA-A receptor agonist,
      muscimol, microinjected into either the dorsal or ventral hippocampus on an
      operant, spatial delayed non-matching-to-position (DNMTP) task were measured. A
      decrease in the number of trials completed per session and disruption of several
      DNMTP discrimination parameters were produced by muscimol microinjection into the
      dorsal hippocampus but not into the ventral hippocampus. Muscimol injected into
      either site did not impair the measure of working memory, delayed choice
      accuracy. These results are consistent with the view that hippocampal function
      varies along the septo-temporal axis, and that the dorsal hippocampus is
      relatively more critical to visual discrimination performance than the ventral
      hippocampus.

PMID- 9518583
TI  - Production of interleukin-12 and expression of its receptors by murine microglia.
AB  - Production of interleukin-12 (IL-12) by cultured murine microglia and astrocytes
      was examined, by means of ELISA to detect heterodimeric p70 and RT-PCR to analyze
      the expression of mRNA encoding p35 and p40. Microglia, but not astrocytes,
      produced IL-12 p70 in response to lipopolysaccharide and interferon-gamma. The
      microglial cell line, Ra2, produced only p40, but not p35, upon above
      stimulation. Thus, it is possible that some population of microglia induce helper
      1 type T cell response via producing IL-12 in the CNS. Microglia were induced to
      express mRNA encoding IL-12 receptors which were exclusively expressed in
      activated T and NK cells.

PMID- 9518584
TI  - Electrolytic lesion of globus pallidus ameliorates the behavioral and
      neurodegenerative effects of quinolinic acid lesion of the striatum: a potential
      novel treatment in a rat model of Huntington's disease.
AB  - Bilateral electrolytic pallidal lesion ameliorated the deleterious effects of
      bilateral quinolinic acid (QA) lesion to the striatum on post-surgery weight,
      activity level, and performance in a water maze task, and reduced the extent of
      striatal damage. Given that the neurodegenerative and behavioral effects of QA
      striatal lesion are thought to mimic those seen in Huntington's disease, these
      results may point to a potential novel treatment for this disease.

PMID- 9518585
TI  - Effects of repeated administration of l-DOPA and apomorphine on circling behavior
      and striatal dopamine formation.
AB  - We tested the circling response to l-DOPA and apomorphine administration in rats
      with unilateral 6-hydroxydopamine (6-OHDA) lesions of the substantia nigra. Rats
      demonstrated a progressively diminished circling response when l-DOPA-carbidopa
      was repeatedly administered at 120 min intervals. This decreasing response was
      not present when apomorphine was administered under the same conditions. We also
      perfused l-DOPA directly into the striatum in vivo of rats with an ipsilateral 6
      OHDA nigrotomy at 60 min intervals and monitored striatal dopamine levels with
      the technique of brain microdialysis. Dopamine formation increased from the first
      to the fifth trial. This may be secondary to the decrease in uptake sites which
      accompanies the loss of striatal dopamine nerve terminals. We postulate that the
      continued presence of dopamine at striatal receptor sites conditions a short-term
      loss of dopamine receptor sensitivity and a consequent decreased circling
      response. The observation that desensitization (as measured by decreasing
      circling) was not present following repeated apomorphine administration may be
      attributable to its shorter duration of action. We also perfused l-DOPA into the
      striatum of normal rats and noted a progressive decrease in striatal dopamine
      levels from the first to the fifth trial. Since this occurred following direct
      administration of l-DOPA into the striatum, the decrease could not be accounted
      for by peripheral pharmacodynamics or bioavailability of l-DOPA in the striatum.
      Since this decrease in dopamine formation was seen only in the normal striatum,
      its relevance to the diminished behavioral response is unclear.

PMID- 9518586
TI  - Cortical facilitation of cutaneous reflexes in leg muscles during human gait.
AB  - During human gait, cortical convergence on sural nerve reflex pathways was
      investigated by means of transcranial magnetic stimulation (TMS) of the cortex in
      five phases of the step cycle during human walking on a treadmill. Muscular
      responses to paired electrical and magnetic stimulation were compared with the
      linear summation of the individual stimuli. For both the tibialis anterior (TA)
      and biceps femoris (BF) muscles, the averaged data of four subjects showed a
      significant facilitation mainly in the swing phase of the step cycle. It is
      suggested that facilitation of corticospinal input onto cutaneous reflex pathways
      is enhanced specifically in these periods of the step cycle.

PMID- 9518587
TI  - Morphological observations on liposomes bearing covalently bound protein: studies
      with freeze-fracture and cryo electron microscopy and small angle X-ray
      scattering techniques.
AB  - The appearance of protein bound to the surface of intact and microfluidized
      liposomes and its possible influence on their morphology was examined by freeze
      fracture electron microscopy, cryo electron microscopy and small angle X-ray
      scattering (SAXS) techniques. Results obtained by the two microscopy techniques
      were in agreement with one another in terms of vesicle size and localization of
      protein (tetanus toxoid or immunoglobulin G) on the surface of vesicles. Surface
      bound protein was observed as particles (10-12 nm diameter) by freeze-fracture
      electron microscopy and was confirmed by immunogold cryo microscopy. SAXS was
      shown to be a suitable means to further characterize liposomes with, or without
      bound protein.

PMID- 9518588
TI  - Painful mononeuropathy in C57BL/Wld mice with delayed wallerian degeneration:
      differential effects of cytokine production and nerve regeneration on thermal and
      mechanical hypersensitivity.
AB  - Wallerian degeneration with macrophage influx and production of proinflammatory
      cytokines is a critical factor in the development of hyperalgesia in animal
      models of neuropathic pain. We hypothesized that in the mouse strain with delayed
      Wallerian degeneration, the C57BL/Wld mouse, the temporal course of mechanical
      allodynia and thermal hyperalgesia as well as the temporal profile of cytokine
      expression after nerve injury would differ from normal mice. Here we used the
      model of chronic constriction injury of the sciatic nerve (CCI) to study the
      correlation of pain related behavior with peripheral nerve de- and regeneration
      and concomitant cytokine production. Indeed, after CCI, C57BL/Wld mice showed
      markedly reduced thermal hyperalgesia compared to normal C57BL/6 mice, temporally
      related to the delayed recruitment of hematogeneous macrophages to the injured
      nerve. Endoneurial tumor necrosis factor-alpha (TNF)-like immunoreactivity
      increased rapidly in normal mice but did so with a delayed time course in
      C57BL/Wld mice. In addition, the duration of mechanical allodynia was
      significantly prolonged in C57BL/Wld mice as compared to C57BL/6 mice, in
      accordance with the delay in regeneration of sensory nerve fibers in these mice.
      These results suggest that macrophage invasion and production of TNF may
      influence the development of thermal hyperalgesia and that regenerative activity
      is linked to mechanical allodynia in peripheral mononeuropathy.

PMID- 9518589
TI  - Effects of dopamine hydrochloride (Inovan(R)) on ouabain-sensitive, K+-dependent,
      p-nitrophenylphosphatase activity of choroid plexus in guinea pigs.
AB  - Dopamine hydrochloride (Inovan(R)) is used for the treatment of acute circulatory
      insufficiency. In the present study, the Na-K ATPase activity of the choroid
      plexus was determined normal and after repeated injections of dopamine
      hydrochloride using cerium-based cytochemistry. In the normal guinea pigs, the
      reaction product was detected on the microvilli of the choroidal epithelium, but
      was almost undetectable after seven repeated injections of dopamine
      hydrochloride. These findings suggested that high doses of dopamine hydrochloride
      decreased the choroidal Na-K ATPase activity.

PMID- 9518590
TI  - Effects of L-DOPA on neuronal activity of the globus pallidus externalis (GPe)
      and globus pallidus internalis (GPi) in the MPTP-treated monkey.
AB  - We studied the effects of L-DOPA on the firing patterns of pallidal neurons in
      experimental parkinsonism. After a unilateral injection of MPTP, we observed a
      decrease in the firing rate of GPe neurons, and a slight increase in their
      bursting activity. In the GPi, there was a considerable augmentation of both
      neuronal firing frequency and the number of bursting cells. During l-DOPA
      treatment (10 mg/kg), GPe neurons.pattern is almost unmodified. The firing
      frequency of GPi neurons, on the contrary, decreased even lower than the control
      level. A slight reduction was observed in bursting activity. These unexpected
      results would show that the normalizing effect of L-DOPA on GPi output is
      limited.

PMID- 9518591
TI  - Formalin-induced release of excitatory amino acids in the skin of the rat
      hindpaw.
AB  - Application of glutamate to skin evokes pain-related behaviors [S.M. Carlton,
      G.L. Hargett, R.E. Coggeshall, Localization and activation of glutamate receptors
      in unmyelinated axons of rat glabrous skin, Neurosci. Lett., 197 (1995) 25-28;
      D.L. Jackson, C.B. Graff, J.D. Richardson, K.M. Hargreaves, Glutamate
      participates in the peripheral modulation of thermal hyperalgesia in rats, Eur.
      J. Pharmacol., 284 (1995) 321-325.] and peripherally-administered glutamate
      antagonists can prevent the nociception produced by inflammation [E.M. Davidson,
      R.E. Coggeshall, S.M. Carlton, Peripheral NMDA and non-NMDA glutamate receptors
      contribute to nociceptive behaviors in the rat formalin test, NeuroReport, 8
      (1997) 941-946; Jackson et al., 1995.] In this study, the concentrations of
      glutamate and aspartate in the plantar of the rat hindpaws were measured before
      and after the subcutaneous administration of formalin. Increases in glutamate and
      aspartate concentrations were observed on the ipsilateral side, but not on the
      contralateral side, to the injection. This shows that nociception and
      inflammation caused by formalin injection induces the release of peripheral
      glutamate and aspartate, which would contribute to nociception and inflammatory
      pain.

PMID- 9518593
TI  - Expression of heparin-binding epidermal growth factor-like growth factor in rat
      brain.
AB  - According to a recent report, messenger RNA coding for a member of the epidermal
      growth factor (EGF) family, heparin-binding EGF-like growth factor (HB-EGF), is
      expressed in the central nervous system (CNS). To obtain information about the
      role of HB-EGF in the brain, we carried out Northern analysis, in situ
      hybridization, and immunohistochemical studies evaluating the distribution and
      amounts of the growth factor using cDNA HB-EGF probes and an antibody raised
      against synthetic HB-EGF propeptide. Northern analysis revealed transcripts for
      HB-EGF in all regions of normal rat brain. Immunohistochemically, HB-EGF was
      demonstrated extensively in neurons at levels varying according to location. HB
      EGF mRNA also was detected in neurons, suggesting that the growth factor is
      produced in these cells. HB-EGF mRNA and immunoreactivity were also demonstrated
      in interfascicular oligodendrocytes. These findings suggest that HB-EGF is a
      physiologic ligand for brain EGF receptors, and is likely to be important in
      neural function.

PMID- 9518592
TI  - Purification by ceftibuten-affinity chromatography and the functional
      reconstitution of oligopeptide transporter(s) in rat intestinal brush-border
      membrane.
AB  - The transport activity of ceftibuten, a dianionic peptide-like compound, was
      extracted from rat intestinal brush-border membrane by n-octylglucoside and
      reconstituted into asolectin liposomes by dialysis. The proteoliposomes prepared
      from the membrane extract showed an inward H+-gradient-dependent uptake of
      ceftibuten and glycylsarcosine. Ceftibuten-immobilized affinity chromatography of
      the membrane extract permitted the isolation of two polypeptides (apparent
      molecular mass of 117 and 127 kDa) that can recognize the dianionic peptide
      structure of ceftibuten. Proteoliposomes prepared from reconstituting the
      isolated proteins into asolectin vesicles showed an overshooting uptake of
      ceftibuten in the presence of an inwardly directed H+ gradient, and this uptake
      could be inhibited by L-valyl-L-proline. N-glycanase digestion of the isolated
      proteins, 117 and 127 kDa, trimmed them into 78 and 120 kDa products,
      respectively. The protein core size of the smaller protein was in agreement with
      the calculated molecular mass of approximately 79 kDa for the rat PepT1
      transporter obtained by other investigators.

PMID- 9518594
TI  - Pharmacological manipulation of hippocampal nitric oxide synthesis affects the
      power of theta recorded from the dorsal hippocampus of urethane-anesthetized rat.

PMID- 9518595
TI  - Cu2+ reveals different binding sites of amiloride and CDPC on the apical Na
      channel of frog skin.
AB  - The effect of Cu2+ ions, present in the mucosal bathing solution, on the
      transepithelial short-circuit current (Isc) and conductance (Gt) and on the
      blocker-induced noise of apical Na channels, was studied on the isolated ventral
      skin of the frog Rana temporaria. Cu2+ effects were concentration-dependent, the
      full effect being reached at 50 micromol/l. Cu2+ increased Isc and Gt; this
      effect was eliminated by high concentrations of amiloride (30 micromol/l) and of
      CDPC (150 micromol/l). Cu2+ markedly reduced the corner frequency (fc) of the Na
      channel noise, while having virtually no effect on the fc of CDPC-induced noise.
      Cu2+ reduces the association rate constant of amiloride to the Na channel to one
      third; this effect is interpreted as indicating competition between Cu2+ and
      amiloride for the same (negatively charged) binding site on the channel, while
      CDPC appears to bind on a different site.

PMID- 9518597
TI  - Proline at position 14 of alamethicin is essential for hemolytic activity,
      catecholamine secretion from chromaffin cells and enhanced metabolic activity in
      endothelial cells.
AB  - Alamethicin is known to lyse different biological cells and to induce voltage
      dependent ion channels in lipid bilayers. A set of analogs with proline shifted
      from position 14 in the native peptide towards the N- and C-terminus was used to
      investigate the role of proline in: (i) alamethicin induced hemolysis of human
      red blood cells, (ii) stimulation of catecholamine secretion from bovine adrenal
      chromaffin cells and (iii) induction of metabolic activity in bovine aortic
      endothelial cells. Half maximal hemolytic activity was found at 30 microM
      alamethicin concentration, complete lysis occurred at 100 microM. The stimulation
      of catecholamine secretion in the presence of extracellular Ca2+ was
      concentration dependent up to 50 microM alamethicin. At this high concentration
      mild secretion was also found in the absence of Ca2+ indicating cell membrane
      damage. Alamethicin transiently stimulated the metabolic rate of endothelial
      cells in a concentration dependent mode up to 20 microM while the inhibition of
      metabolism at higher concentrations pointed to a toxic effect. The alamethicin
      analogs were completely inactive in all the biological assays. The effects
      correlated with a loss of dye release inducing activities on phosphatidylcholine
      vesicles and reduction of channel forming properties in lipid bilayers and were
      associated with modifications of membrane affinity rather than conformational
      changes of the peptides. The results indicate that proline at position 14 of the
      native peptide is essential for the interaction with different membrane systems.

PMID- 9518596
TI  - Acute sodium depletion modifies septo-preoptic neuron sensitivities to
      neurohormones.
AB  - Sodium (Na+) depletion induces sodium appetite to replenish Na+ loss. It appears
      to be a consequence of enhanced levels of aldosterone (Aldo) and angiotensin II
      (AII) in the plasma as well as in the brain. Mineralocorticoid pretreatment
      modifies the sensitivity of septo-preoptic neurons to locally applied AII and
      Aldo. Therefore, we investigated septo-preoptic neuronal sensitivities to AII and
      Aldo, as well as to the specific AII type-1 receptor (AT-1) non-peptide
      antagonist losartan (Los) and to the specific AII type-2 receptor (AT-2) non
      peptide antagonist PD123319 after one Na+ depletion without repletion. We found
      that one Na+ depletion induced increases in the proportion of neurons inhibited
      by iontophoretic application of AII (20.5% vs. 7.8%, p=0.004) whereas, the
      proportion of neurons excited by Aldo was increased, (23.7% vs. 5%, p=0.001).
      Moreover, the proportion of neurons changing sensitivity to AII after one
      application of Aldo was increased in the furosemide group (44.2% vs. 20.4%,
      p=0.0123). The proportion of neurons inhibited by application of losartan was
      enhanced, (26.4% vs. 9.3%, p=0.03). No significant changes were found in response
      to PD123319 by itself. Moreover, there were more neurons which co-localized
      responses to both Los and PD123319 in the furosemide group than in the control
      group (29.7% vs. 8.6%, p=0.027). It is known that multidepletions induce an
      increased need-free sodium appetite and our present findings could well form part
      of the neuronal basis of this behavior.

PMID- 9518598
TI  - Electron transfer in the heliobacterial reaction center: evidence against a
      quinone-type electron acceptor functioning analogous to A1 in photosystem I.
AB  - Membrane fragments from Heliobacillus mobilis were characterized using time
      resolved optical spectroscopy and photovoltage measurements in order to detect a
      possible participation of menaquinone (MQ), functioning analogous to the
      phylloquinone A1 in photosystem I, as intermediate in electron transfer from the
      primary acceptor A0 to the iron-sulfur cluster FX in the photosynthetic reaction
      center. The spectroscopic data obtained exclude that electron transfer from a
      semiquinone anion MQ- to FX occurred in the time window from 2 ns to 4 micros,
      where it would be expected in analogy to photosystem I. In the case of a
      prereduction of FX, only the primary pair P798+A0- was formed. The photovoltage
      data yielded a single kinetic phase with a time constant of 700 ps for the
      transmembrane electron transfer beyond A0; the relative amplitude of this phase
      suggests that it reflects electron transfer from A0- to FX.

PMID- 9518599
TI  - Serotoninergic innervation of stapedial and tensor tympani motoneurons.
AB  - Retrograde tracing and neurotransmitter immunohistochemistry were combined to
      determine whether serotonin neurons innervated stapedial and tensor tympani
      motoneurons. With high-power light microscopy, putative axo-somatic and axo
      dendritic contacts were observed between serotonin-positive endings and both
      stapedial and tensor tympani motoneurons, indicating that serotonin neurons
      terminate on brainstem motoneurons innervating the middle-ear muscles. With this
      connection, the serotonin system may directly modulate middle-ear muscle
      activity.

PMID- 9518600
TI  - Modulatory and direct effects of propofol on recombinant GABAA receptors
      expressed in xenopus oocytes: influence of alpha- and gamma2-subunits.
AB  - Propofol (2,6-diisopropylphenol) is an intravenous general anaesthetic which can
      directly activate and positively modulate the GABAA receptor. The effects of
      propofol on human recombinant GABAA receptors were studied in Xenopus oocytes
      expressing either alpha1beta2, alpha1beta2gamma2L, or alpha2beta2gamma2L receptor
      isoforms. In all receptor isoforms tested, propofol was able to potentiate the
      GABA-activated currents in a concentration-dependent manner. Although propofol
      potentiated both alpha1beta2 and alpha1beta2gamma2L receptor isoforms with equal
      affinity, the efficacy of propofol potentiation was markedly greater in the
      alpha1beta2 receptor isoform. In contrast, potentiation of the alpha2beta2gamma2L
      receptor isoform by propofol occurred with higher affinity and lower efficacy
      than in the alpha1beta2gamma2L receptor isoform. Propofol directly activated all
      three receptor isoforms in a concentration dependent manner. Addition of the
      gamma2L subunit subtype to the alpha1beta2 receptor isoform decreased receptor
      sensitivity to direct activation by propofol. Replacement of the alpha1-subunit
      subtype with the alpha2-subunit subtype increased receptor sensitivity to
      propofol's direct effects. These results suggest that the alpha-and gamma2L
      subunit subtypes each have the ability to influence both the direct and
      modulatory actions of propofol on GABAA receptor function.

PMID- 9518602
TI  - Light-induced structural changes in photosynthetic reaction centres studied by
      ESEEM of spin-correlated D+QA- radical pairs.
AB  - Zn-substituted Rhodobacter sphaeroides R26 reaction centres (RCs) frozen in the
      dark and under illumination exhibit quite different recombination kinetics of the
      D+QA- radical pairs [Kleinfeld et al., Biochemistry, 23 (1984) 5780]. We have
      applied electron spin echo envelope modulation (ESEEM) of the spin-correlated
      D+QA- radical pairs to assess a possible light-induced change in the distance
      between the D and QA cofactors. The recombination kinetics and the field-swept
      spin-polarized EPR signal for the two preparations have been monitored by time
      resolved EPR spectroscopy. For the samples frozen under illumination, a slight
      increase in the distance, 0.4+/-0.2 A, has been detected.

PMID- 9518601
TI  - Metabolic mapping of the rat brain after subanesthetic doses of ketamine:
      potential relevance to schizophrenia.
AB  - Subanesthetic doses of ketamine have been shown to exacerbate symptoms in
      schizophrenia and to induce positive, negative, and cognitive schizophrenic-like
      symptoms in normal subjects. The present investigation sought to define brain
      regions affected by subanesthetic doses of ketamine, using high resolution
      autoradiographic analysis of 14C-2-deoxyglucose (2-DG) uptake and
      immunocytochemical staining for Fos-like immunoreactivity (Fos-LI). Both
      functional mapping approaches were used because distinct and complementary
      information is often obtained with these two mapping methods. Ketamine, at a
      subanesthetic dose of 35 mg/kg, substantially increased 2-DG uptake in certain
      limbic cortical regions, including medial prefrontal, ventrolateral orbital,
      cingulate, and retrosplenial cortices. In the hippocampal formation, the
      subanesthetic dose of ketamine induced prominent increases in 2-DG uptake in the
      dentate gyrus, CA-3 stratum radiatum, stratum lacunosum moleculare, and
      presubiculum. Increased 2-DG uptake in response to 35 mg/kg ketamine was also
      observed in select thalamic nuclei and basolateral amygdala. Ketamine induced Fos
      LI in the same limbic cortical regions that exhibited increased 2-DG uptake in
      response to the subanesthetic dose of the drug. However, no Fos was induced in
      some brain regions that showed increased 2-DG uptake, such as the hippocampal
      formation, anterioventral thalamic nucleus, and basolateral amygdala. Conversely,
      ketamine induced Fos in the paraventricular nucleus of the hypothalamus and
      central amygdala, although no effect of the drug on 2-DG uptake was apparent in
      these regions. In contrast to the increase in 2-DG uptake observed in select
      brain regions after the subanesthetic dose, an anesthetic dose of ketamine (100
      mg/kg) produced a global suppression of 2-DG uptake. By contrast, a robust
      induction of Fos-LI was observed after the anesthetic dose of ketamine that was
      neuroanatomically identical to that produced by the subanesthetic dose. Results
      of the present investigation show that anesthetic and subanesthetic doses of
      ketamine have pronounced effects on regional brain 2-DG uptake and induction of
      Fos-LI. The alterations in regional brain metabolism induced by the subanesthetic
      dose may be relevant to effects of ketamine to induce schizophrenic-like
      symptoms.

PMID- 9518604
TI  - Response of a cell-surface NADH oxidase to the antitumor sulfonylurea N-(4
      methylphenylsulfonyl)-N'-(4-chlorophenylurea) (LY181984) modulated by redox.
AB  - In previous reports, our laboratory has described a drug-responsive NADH oxidase
      activity of the external surface of the plasma membrane of HeLa and other cancer
      cells, but not from normal cells, that was shed into media conditioned by the
      growth of cancer cells such as HeLa and also into sera of cancer patients. The
      sulfonylurea-altered activity was found in sera of a wide variety of cancer
      patients but the activity was either inhibited or stimulated by 1 microM
      LY181984. In this report, we demonstrate that one basis for whether or not the
      activity was stimulated or inhibited may be the redox environment of the protein.
      If plasma membrane vesicles from HeLa cells were first treated with
      dithiothreitol (DTT) or with reduced glutathione (GSH) and then assayed for NADH
      oxidase activity, the sulfonylurea inhibited the activity in a concentration
      dependent manner. In contrast, if the plasma membrane vesicles were first treated
      with diluted hydrogen peroxide or oxidized glutathione (GSSG) and then assayed
      for NADH oxidase activity, the antitumor sulfonylurea stimulated the activity.
      Growth experiments were conducted in parallel. LY181984 administered to HeLa
      cells in the presence of GSH was approximately 2 log orders more effective than
      LY181984 administered to HeLa cells in the presence of GSSG. Similar results were
      found in the sera of cancer patients. With sera from normal individuals or with
      plasma membranes of rat liver, the oxidizing or reducing conditions were without
      effect. The findings suggest that the response of the cell surface NADH oxidase
      of HeLa cells to the antitumor sulfonylurea LY181984 is influenced by the redox
      environment which may determine whether the drug will stimulate or inhibit the
      activity and that the degree of response may be reflected in the ability of
      LY181984 to inhibit HeLa cell growth.

PMID- 9518605
TI  - Bilateral projections of the pontine micturition center to the sacral
      parasympathetic nucleus in the rat.
AB  - Previous work has revealed that pontine micturition center (PMC) neurons send
      projections to the sacral parasympathetic nucleus (SPN) of the intermediolateral
      (IML) regions of L6-S1 spinal cord segments in rats. Although unilateral SPN
      injections will retrogradely label PMC neurons bilaterally, it is not known
      whether single PMC neurons project bilaterally to the SPN. There may be two
      different populations of PMC neurons on each side of the brainstem, with both
      groups independently connecting to the SPNs on opposite sides of the spinal cord.
      To verify one of these alternatives, a small injection of either rhodamine
      labeled latex microspheres or a red fluorescent emulsion was made into the SPN on
      one side of the cord; a similar injection of either fluorescein-tagged
      microspheres or a green fluorescent emulsion was made into the other. After at
      least seven days, the rats were perfused. Inspection of 40 micron cord sections
      confirmed the similar placement of these injections along the rostrocaudal axis
      of the cord and that no tracer had spread across midline. Thirty-micron brain
      sections were examined for filled neurons. Red, green and double labeled neurons
      were found bilaterally in the PMC, subcoeruleus, and A5 regions. Although some
      red nucleus cells were also filled, they were only singly labeled and always
      located contralateral to the injection. Finally, immunohistochemical staining of
      dopamine-beta-hydroxylase (DBH) containing cells confirmed that some labeled
      cells were also noradrenergic. We therefore conclude that some PMC, subcoeruleus,
      and A5 neurons send axons to the SPN on both sides of the lumbosacral cord.

PMID- 9518607
TI  - Determination of distances from tyrosine D to QA and chlorophyllZ in photosystem
      II studied by '2+1' pulsed EPR 
AB  - A '2+1' pulse sequence electron spin echo (ESE) method was applied to measure the
      dipole interactions between the tyrosine YD+ and QA- in Photosystem II (PS II).
      In a CN--treated PS II, QA- EPR signal was observed at g=2.0045 position, because
      the non-heme Fe(II) was converted into a low-spin (S=0) state. The radical pair
      of YD+QA- was trapped by illumination for 8 min at 273 K, followed by dark
      adaptation for 3 min and freezing into 77 K. By using a proton matrix ENDOR,
      these trapped radicals were confirmed to be YD+ and QA-, respectively. The
      distance between the radical pair was estimated from the dipole interaction
      constant fitted to the observed '2+1' ESE time profile. The distance of YD+-QA-
      is determined to be 38.8+/-1.1 A. The magnetic dipole interaction between YD+ and
      ChlZ+ was determined in a Tris-treated PS II in which ChlZ+ was generated by
      illumination at 200 K for 10 min. The YD+-ChlZ+ distance was estimated to be
      29.4+/-0.5 A. Copyright 1998 Elsevier Science B.V.

PMID- 9518606
TI  - Evidence for physiologically active axonal adenosine receptors in the rat corpus
      callosum.
AB  - Several neurotransmitter receptors have been identified on axons, and emerging
      evidence suggests that central axonal conduction may be modulated by
      neurotransmitters. We have recently demonstrated the presence of extra-synaptic
      adenosine Al receptors along rat hippocampal axons. We now present
      immunocytochemical evidence for Al receptors on rat corpus callosum axons and
      show that these receptors actively modulate axon physiology. Using rat brain
      coronal slices, we stimulated the corpus callosum and recorded the evoked
      extracellular compound action potential. The lipid-soluble, Al-specific adenosine
      receptor agonist cyclopentyladenosine, dose-dependently decreased the compound
      action potential amplitude, an effect reversed by the specific Al antagonist 8
      cyclopentyl-1, 3-dipropylxanthine. These data provide the first direct evidence
      that axonal Al adenosine receptors modulate axon physiology in the adult
      mammalian brain. Influencing axonal transmission is a potentially powerful
      mechanism of altering information processing in the nervous system.

PMID- 9518608
TI  - The retinal ganglion cells that drive the pupilloconstrictor response in rats.
AB  - It is well established that the pupillary light reflex (PLR) in rats is mediated
      by a direct retinal projection to the olivary pretectal nucleus (OPN). Although
      several authors have commented on the specific subpopulation of retinal ganglion
      cells (RGC) that project to the rat pretectum, much of this evidence is
      circumstantial, and depends mostly upon electrophysiological data (e.g.,
      conduction velocity). Here, we have used microinjections of Fluoro-Gold into the
      OPN (pretectum and superior colliculus as controls) to retrogradely label RGCs
      projecting to this region. The retinae were whole-mounted, viewed under
      fluorescence, and the regional distribution pattern, laterality of projection,
      and cell soma sizes determined. The results show OPN injections label a small
      subpopulation of RGCs. In the contralateral retinae, labeled RGCs were most
      numerous and widespread, with 97% projecting to the contralateral pretectum. The
      highest density of cells in the contralateral retinae was found in the inferior
      and nasal retinal quadrants. In the ipsilateral retinae, the small number of
      labeled cells were concentrated in the periphery of the inferior and nasal
      retinal quadrants. A striking feature of both ipsilateral and contralateral
      retinae was the paucity of labeled cells found in the dorsal hemiretina (lower
      visual field). Cell size measurements indicate 90-95% of labeled RGCs had
      diameters of 9-13 microm, while most of the remaining cells had diameters of 20
      25 microm. This would suggest class III cells may be the predominant RGC type
      mediating pupilloconstriction, although a smaller population of larger cells
      (e.g., class I and/or II) may also contribute to this pathway. The recent reports
      utilizing the PLR as an assay for the efficacy of intraretinal grafts has
      highlighted the significance of the regional distribution results. The extremely
      low number of labeled cells in the dorsal hemiretina would argue for the
      placement of such grafts in the ventral hemiretina.

PMID- 9518609
TI  - On the effect of 2-deuterium- and 2-methyl-eicosapentaenoic acid derivatives on
      triglycerides, peroxisomal beta-oxidation and platelet aggregation in rats.
AB  - A series of 2-substituted eicosapentaenoic acid (EPA) derivatives (as ethyl
      esters) have been synthesized and evaluated as hypolipidemic and antithrombotic
      agents in feeding experiments in rats. Repeated administration of purified 2
      methyl-eicosapentaenoic acid and its deuterium analogues (all as ethyl esters) to
      rats resulted in a decrease in plasma triglycerides and high density lipoprotein
      cholesterol. The 2-methyl-EPA analogues were, apparently, four times more potent
      than EPA in inducing the triglyceride lowering effect. The 2-deuterium-2-methyl
      EPA decreased plasma cholesterol level to approximately 40%. A moderate
      enlargement of the liver was observed in 2-methyl-EPA treated rats. This was
      accompanied with an acute reduction in the liver content of triglycerides and a
      stimulation of peroxisomal beta-oxidation and fatty acyl-CoA oxidase activity.
      The results suggest that the triglyceride-lowering effect of 2-methyl-EPA may be
      due to a reduced supply of fatty acids for hepatic triglyceride biosynthesis
      because of increased fatty acid oxidation. Platelet aggregation with ADP and
      A23187 was performed ex vivo in platelet-rich plasma, after administration of
      different doses of the EPA-derivatives for five days. EPA and 2,2-dideuterium EPA
      had no effect on ADP-induced aggregation, while 2-deuterium-, 2-methyl- and 2
      deuterium-2-methyl EPA produced a biphasic effect, i.e. potentiation and
      inhibition at low (250 mg/day kg body weight) and higher doses (600-1300 mg/day
      kg body weight), respectively. A23187-induced platelet aggregation was affected
      in a similar way by feeding the 2-substituted EPA derivatives, except that 2
      deuterium-2-methyl EPA had no effect relative to EPA itself and that the
      inhibition was far greater than that for ADP-induced aggregation (approximately
      100% inhibition with 600 mg 2-methyl-EPA/day kg body weight). The ranking order
      of the EPA-derivatives to affect platelet aggregation and to cause hypolipidemia
      was different, suggesting different mechanisms. Our observations suggest that the
      effects of the EPA derivatives on platelet aggregation could be related to the
      degree of bulkiness around C2 and that an asymmetric substitution at C2 caused
      inhibition of platelet aggregation while a symmetric substitution did not. It is
      suggested that the bulky, asymmetric derivatives inhibit platelet aggregation by
      altering platelet membrane phospholipid packing.

PMID- 9518610
TI  - Amyloid-beta peptide activates cultured astrocytes: morphological alterations,
      cytokine induction and nitric oxide release.
AB  - A common feature of many neurodegenerative disorders is an abundance of activated
      glial cells (astrocytes and microglia). In Alzheimer's disease (AD), activated
      astrocytes are in close apposition to and surrounding the amyloid plaques. The
      mechanisms by which the astrocytes become activated in AD and the consequences of
      reactive astrocytosis to disease progression are not known. We examined the
      possibility that the amyloid-beta (Abeta) peptide, a major constituent of the
      amyloid plaque, could act as a stimulus leading to activation. We found that
      treatment of rat cortical astrocyte cultures with aggregated Abeta 1-42 peptide
      induces activation, as assessed by reactive morphological changes and
      upregulation of selective glial mRNA and proteins, such as the inflammatory
      cytokine interleukin-1beta. Abeta also stimulates inducible nitric oxide synthase
      (iNOS) mRNA levels and nitric oxide (NO) release. Abeta 1-42, a major form of
      amyloid associated with neurotoxicity, activated astrocytes in a time- and dose
      dependent manner, whereas a scrambled Abeta 1-42 sequence or Abeta 17-42 had
      little or no effect. We also determined that the Abeta activity can be found in a
      supernatant fraction containing soluble Abeta oligomers. Our data suggest that
      Abeta plays a role in the reactive astrocytosis of AD and that the inflammatory
      response induced upon glial activation is a critical component of the
      neurodegenerative process.

PMID- 9518611
TI  - The cortico-related zones of the rabbit claustrum-study of the claustrocortical
      connections based on the retrograde axonal transport of fluorescent tracers.
AB  - The claustrocortical connections in the rabbit were assessed for the first time
      by the method of axonal retrograde transport of two fluorescent tracers (Fast
      Blue and Diamidino Yellow). The material consisted of 23 adult New Zealand
      rabbits. Projection zones of spindle-like form, connected with the precentral,
      postcentral, temporal and occipital cortices have been delineated. They are
      organized topographically both in the anteroposterior and ventrodorsal direction.
      The precentral (motor) projection zone is localized in the anterodorsal part of
      the claustrum. It may be divided into two separate parts that project to the
      medial and lateral part of the precentral cortex. The large postcentral
      (somatosensory) zone occupies mainly the central part, whereas the temporal
      (auditory) and occipital (visual) zones are situated in the posteroventral part
      of the claustrum. The overlap of various claustral projection zones is
      differentiated, the largest being that of the somatosensory zones. In comparison
      to the results of study of claustral projection zones performed on other species,
      presumably on the rat and cat, its seems plausible to conclude that the extension
      of claustral projection zones and degree of their overlap in the rabbit represent
      an intermediate character.

PMID- 9518612
TI  - Redox properties of an H-subunit-depleted photosynthetic reaction center from
      Rhodopseudomonas viridis.
AB  - Recently, we reported that a H-subunit-depleted photosynthetic reaction center
      (RC-H) was purified from purple nonsulfer photosynthetic bacterium
      Rhodopseudomonas viridis (Rps. viridis) using a strong detergent sodium alkyl
      ether sulfate. We compared the redox properties of a native photosynthetic
      reaction center (RC) and RC-H of Rps. viridis. In RC-H prepared by our method,
      secondary quinone (QB) was removed while primary quinone (QA) was retained.
      Absorption spectrum of RC-H was similar to that of RC. After reconstitution of
      ubiquinone 10 into QB sites, RC-H showed electron transfer activity that was the
      same as that for native RC. This is the first report about the redox properties
      of RC-H of Rps. viridis.

PMID- 9518613
TI  - Experimentally induced muscle pain induces hypoalgesia in heterotopic deep
      tissues, but not in homotopic deep tissues.
AB  - The ability of muscle pain to generate somatosensory sensibility changes is
      controversial. Thus, in the present study, tonic infusion of hypertonic saline
      (5%, 7.1 ml administered over 15 min) into the tibialis anterior (TA) muscle was
      used as an experimental model to induce local and referred pain. The sensibility
      to high-intensity pressure stimuli applied to the local pain area, referred pain
      area and an arm was assessed in 14 healthy volunteers. Infusion of isotonic
      (0.9%) saline into the other leg served as control. The subject continuously
      scored the pain intensity on an electronic visual analogue scale (VAS). Pressure
      pain threshold (PPT) was determined on the TA muscle (2 cm and 10 cm from the
      infusion site), at the frontal aspect of the ankle (area of referred pain) and on
      the arm. To minimise the skin component of the PPT, the skin covering the
      assessment sites was anaesthetised with an anaesthetic creme. The PPTs were
      obtained before and after cutaneous analgesia, 1 min and 10 min after infusion
      start and 10 min after the pain had disappeared. Infusion of hypertonic saline
      caused significantly (P<0. 05) higher VAS scores than infusion of isotonic
      saline. A significant (P<0.04) increase of the PPT (i.e., decreased sensibility)
      was found at the ankle and on the arm during muscle pain compared to the control
      condition. No significant differences in PPTs on the TA muscle were found during
      saline-induced muscle pain compared to the infusion of isotonic saline. The
      decrease in deep sensibility at the heterotopic sites (referred pain area and
      arm), but not at homotopic sites (TA muscle), probably reflected the phenomenon
      of diffuse noxious inhibitory control (DNIC). The inhibitory mechanism during
      muscle pain was shown to be effective for the deep tissue sensibility in healthy
      subjects. Thus, a pathologically disturbed inhibitory mechanism may result in
      widespread deep hyperalgesia in muscle pain patients.

PMID- 9518614
TI  - Chronopotentiometric studies of electroporation of bilayer lipid membranes.
AB  - The constant-intensity current chronopotentiometric measurements of egg yolk
      phosphatidylcholine bilayer membranes (BLM) are presented. It is demonstrated
      that a constant-intensity current flowing through the bilayer membranes generates
      the pores in their structures. For the current intensity from 0.1 to 2.0 nA, the
      generated pores open and close cyclically. The frequency of oscillations depends
      on the current intensity: the higher current intensity, the higher frequency of
      pore oscillations. It is suggested that the presented method may allow to create
      one pore in BLM and to observe its dynamical behaviour. Based on
      chronopotentiometric curves, a method of pore conductance calculations is
      presented. It is demonstrated that the value of obtained conductance can be
      applied for pore diameter estimation. The hypothetical application of constant
      current method as a biotechnological tool for selective and controlled
      incorporation of molecules into microorganisms is discussed.

PMID- 9518615
TI  - The expression of P- and E-selectins in three models of middle cerebral artery
      occlusion.
AB  - The expression and localization of P- and E-selectins in rat brain (n=126) were
      examined using immunohistochemical techniques at various time points after
      induction of middle cerebral artery (MCA) occlusion in the suture, thrombotic and
      embolic models of stroke. Expression of P- or E-selectin was not observed in
      brain tissue of sham operated control rats (n=9). P-selectin immunoreactivity was
      detected as early as 15 min and decreased to control level at 1 h after the onset
      of the MCA occlusion in all three models. P-selectin then slightly increased at 2
      h and peaked at 6 h after MCA occlusion. E-selectin immunoreactivity was first
      observed at 2 h and peaked at 6 h and 12 h of after MCA occlusion in all three
      models. P- and E-selectin immunoreactivity was colocalized with von Willebrand
      factor immunoreactive microvessels. 90.4+/-2.0% of all vessels expressing P
      selectin immunoreactivity were 7.5 to 30.0 micron in diameter; 3.6+/-1.4% were
      contained in vessels smaller than 7.5 micron, and 6.0+/-1.8% were localized in
      vessels greater than 30.0 micron in diameter. The percent distribution of E
      selectin immunoreactive vessels were 75.9+/-2.1% in vessels 7.5 to 30.0 micron in
      diameter; 23.6+/-2.2% were in vessels smaller than 7.5 micron, and 0.6+/-0.4%
      were localized in vessels greater than 30.0 micron in diameter. These findings
      indicate that the temporal profiles of P- and E-selectin expression are
      independent of these models of MCA occlusion and are consistent with the time
      course of selectin mediated leukocyte infiltration after focal cerebral ischemia
      in the rat.

PMID- 9518616
TI  - Cerebral vessels express interleukin 1beta after focal cerebral ischemia.
AB  - Rapid and marked increased levels of expression of interleukin 1beta (IL-1beta)
      mRNA have been detected in animal models of cerebral ischemia. However, the
      protein production of IL-1beta and the cellular sources of IL-1beta are largely
      undefined after cerebral ischemia. In the present study, we have measured the
      cellular localization of IL-1beta protein in brain tissue from non-ischemic and
      ischemic mice using immunohistochemistry. Male C57B/6J (n=45) mice were subjected
      to middle cerebral artery (MCA) occlusion by a clot or a suture. The mice were
      sacrificed at time points spanning the period from 15 min to 24 h after onset of
      the MCA occlusion. Non-operated and sham-operated mice were used as control
      groups. A monoclonal anti-IL-1beta antibody was used to detect IL-1beta. In the
      non-operated and sham-operated mice, a few IL-1beta immunoreactive cells were
      detected scattered throughout both hemispheres. IL-1beta immunoreactive cells
      increased in the ischemic lesion as early as 15 min and peaked at 1 h to 2 h
      after MCA occlusion. IL-1beta immunoreactivity was detected in the cortex of the
      contralateral hemisphere 1 h after ischemia. By 24 h after onset of ischemia, IL
      1beta immunoreactivity was mainly present adjacent to the ischemic lesion and in
      the non-ischemic cortex. IL-1beta immunoreactivity was found on endothelial cells
      and microglia. This study demonstrates an early bilateral expression of IL-1beta
      on endothelium after MCA occlusion in mice.

PMID- 9518617
TI  - Periodate-oxidized ATP stimulates the permeability transition of rat liver
      mitochondria.
AB  - Periodate-oxidized ADP (oADP)2 and periodate-oxidized ATP (oATP) stimulate the
      permeability transition in energized rat liver mitochondria measured as the Ca2+
      efflux induced by Ca2+ and Pi. In the presence of Mg2+ and Pi, mitochondria lose
      intramitochondrial adenine nucleotides at a slow rate. oATP induces a strong
      decrease of the matrix adenine nucleotides which is inhibited by
      carboxyatractyloside. Under these conditions, Mg2+ prevents the opening of the
      permeability transition pore. EGTA prevents the Pi-induced slow efflux of adenine
      nucleotides, but is without effect on the oATP-induced strong decrease of adenine
      nucleotides. This oATP-induced strong adenine nucleotide efflux is inhibited by
      ADP. oATP reduces the increase of matrix adenine nucleotides occurring when the
      mitochondria are incubated with Mg2+ and ATP. This effect of oATP is also
      prevented by carboxyatractyloside. oATP is not taken up by the mitochondria. It
      is suggested that oATP induces a strong efflux of matrix adenine nucleotides by
      the interaction with the ADP/ATP carrier from the cytosolic side. The induction
      of the mitochondrial permeability transition by oADP and oATP is attributed to
      two mechanisms-a strong decrease in the intramitochondrial adenine nucleotide
      content, especially that of ADP, and a stabilization of the c-conformation of the
      ADP/ATP carrier.

PMID- 9518618
TI  - The levels of adenosine and its metabolites in the guinea pig and rat brain
      during complete ischemia-in vivo study.
AB  - Changes in levels of adenosine, inosine, hypoxanthine and ATP during complete
      ischemia after decapitation were determined in various areas of the guinea pig
      and rat brain using an HPLC method. These results were compared with levels in
      brains fixed by microwave irradiation. The levels of adenosine during 60 min of
      complete ischemia were extremely high and unevenly distributed while levels in
      the microwaved brains were very low and evenly distributed. The ratios of inosine
      plus hypoxanthine levels to adenosine which indicate the rate of metabolic
      degradation from adenosine into inosine and hypoxanthine, were also unevenly
      distributed during complete ischemia in the cerebellum, superior colliculus,
      cerebral cortex and hippocampus of the guinea pig and rat, and the highest ratio
      was observed in the cerebellum of the guinea pig and the superior colliculus of
      the rat. The activities of adenosine deaminase (ADA), one of the enzymes involved
      in adenosine metabolism, were measured in the four regions of the guinea pig. The
      ADA activities were unevenly distributed and the highest ADA activity was found
      in the cerebellum. These regional differences in ADA activities are in good
      agreement with the regional differences in the ratio of inosine plus hypoxanthine
      levels to adenosine during complete ischemia. Furthermore, the administration of
      EHNA [erythro-9-(2-hydroxy-3-nonyl)adenine hydrochloride] (10 mg/kg, i.p.), an
      ADA inhibitor, caused a significant increase of adenosine and decrease of inosine
      formation in all four regions and a drastic effect on the cerebellum with high
      ADA activity compared with the other regions in the guinea pig brain. These
      results indicate that the changes in concentrations of adenosine and its
      metabolites (inosine and hypoxanthine) during complete ischemia depend on ADA
      activity in each brain region.

PMID- 9518619
TI  - A new Na+/H+ antiporter, NhaD, of Vibrio parahaemolyticus.
AB  - A gene encoding an Na+/H+ antiporter was cloned from chromosomal DNA of Vibrio
      parahaemolyticus, a slightly halophilic bacterium, and expressed in Escherichia
      coli cells. The gene enabled mutant E. coli cells, which were unable to grow in
      the presence of 10 mM LiCl (or 0.2 M NaCl) because of the lack of major
      Na+(Li+)/H+ antiporters, to grow under such conditions. We detected Na+/H+
      antiport activity due to the gene in membrane vesicles prepared from E. coli
      cells that harbored the plasmid carrying the gene. Li+ was also a substrate for
      this antiporter. Activity of this antiporter was pH-dependent with highest
      activity at pH 8.5 to 9 and no activity at 7.0 to 7.5. Restriction mapping and a
      Southern blot analysis revealed that the cloned gene was different from the nhaA
      and the nhaB of V. parahaemolyticus. We designated the gene nhaD. The gene was
      sequenced, and the amino acid sequence of the NhaD protein was deduced. The NhaD
      is a unique Na+/H+ antiporter with respect to the primary structure compared with
      known Na+/H+ antiporters.

PMID- 9518620
TI  - Immunocytochemical distribution of angiotensin I-converting enzyme-like
      immunoreactivity in the brain and testis of insects.
AB  - Angiotensin converting enzyme (ACE) is Zn2+ metallopeptidase which plays an
      important role in blood pressure homeostasis in mammals and other vertebrates.
      Homologues of ACE involved in the biosynthesis of mammalian peptide hormones have
      also been identified in the insects, Musca domestica, Drosophila melanogaster and
      Haematobia irritans exigua. In the pursuit of the biological role of insect ACE,
      this work focused on the tissue and cellular distribution of ACE in several
      insect species. The localisation of ACE in the central nervous system and
      reproductive tissues from a number of insect species suggests that ACE is of
      physiological importance in these tissues. By means of an antiserum to housefly
      ACE, we found that ACE-like immunoreactivity was abundantly present in the
      neuropil areas of the brain of all insects investigated, suggesting a role for
      ACE in the metabolic inactivation of peptide neurotransmitters. Especially in the
      fleshfly, Neobellieria bullata neuropile staining is abundant. In the cockroach
      Leucophaea maderae, immunoreactive staining was abundant in the neuronal
      perikarya as well as in the neuropilar regions. Staining in neurosecretory cells
      was also observed in the brains of the lepidopteran species, Bombyx mori and
      Mamestra brassica. The localisation of ACE in neurosecretory cells is consistent
      with the role as a processing hormone, involved in the generation of active
      peptide hormones. ACE was found to be co-localised with peptides of the
      FXPRLamide family in M. brassica and in B. mori, suggesting a role for the
      biosynthesis of these hormones. Finally, we found ACE-like immunoreactivity in
      the testis of Locusta migratoria, N. bullata and Leptinotarsa decemlineata,
      providing additional evidence for its important role in insect reproduction.

PMID- 9518621
TI  - Glutamate residues at positions 219 and 252 in the a-subunit of the Escherichia
      coli ATP synthase are not functionally equivalent.
AB  - The role of glutamate-219 in the a-subunit of the Escherichia coli F0F1-ATPase
      was examined using site-directed mutagenesis. The replacement of Glu-219 by
      lysine, alanine or glycine resulted in a partially functional F0F1-ATPase.
      Combining any of these mutations with the substitution of glutamate for Gln-252
      did not result in any increase in function. These findings rule out a proposal
      that glutamate at position 252 can functionally replace glutamate at position 219
      [S.B. Vik, B.J. Antonio, J. Biol. Chem. 269 (1994) 30364-30369]. All the single
      and double mutants grew better at 25 degrees C than at 37 degrees C, suggesting a
      role for Glu-219 in maintaining the structure of the F0.

PMID- 9518622
TI  - Acetylcholine release from the frontal cortex during exploratory activity.
AB  - The activation of the cortical cholinergic system was investigated in 3- and 25
      month-old male Wistar rats, by measuring by transversal microdialysis the changes
      in cortical extracellular acetylcholine (ACh) levels during the performance of
      simple spontaneous tasks involving exploratory activity and working memory. Two
      days after implantation of the microdialysis probe in the frontal cortex, object
      recognition was investigated by either moving the rats from the home cage to the
      arena containing the objects or keeping the rats in the arena and introducing the
      objects. Spontaneous alternation was investigated in a Y runway. Young rats
      discriminated between familiar and novel objects and alternated in the Y runway,
      while aged rats were unable to discriminate. Whenever rats were moved from the
      home cage to the arena, ACh release increased (+70-80%) during the exploratory
      activity. Handling per se had no effect on extracellular ACh levels. When young
      rats were left in the arena, introduction of the objects caused some exploratory
      activity and object recognition but no increase in ACh release. ACh release
      increased by about 300% during spontaneous alternation. In aging rats basal
      extracellular ACh levels and their increase after placement in the arena were
      less than half that in young rats. Our work demonstrates that a novel environment
      activates the cortical cholinergic system, which presumably is associated with
      arousal mechanisms and selective attentional functions. It also demonstrates that
      in aging rats the cortical cholinergic hypofunction is associated with a loss of
      non-spatial working memory.

PMID- 9518625
TI  - Fiber-type-related differences in the enzymes of a proposed substrate cycle.
AB  - A substrate cycle between citric acid cycle (CAC) intermediates isocitrate and 2
      oxoglutarate, involving NAD+- and NADP+-linked isocitrate dehydrogenase (NAD-IDH
      and NADP-IDH, respectively) and mitochondrial transhydrogenase (H+-Thase), has
      recently been proposed. This cycle has been hypothesized to enhance mitochondrial
      respiratory control by increasing the sensitivity of NAD-IDH to its modulators
      and allowing for enhanced increases in flux through this step of the CAC during
      periods of increased ATP demand. The activities of the enzymes comprising the
      substrate cycle: NAD-IDH, forward and reverse NADP-IDH, and forward and reverse
      H+-Thase, along with the activity of a marker of mitochondrial content, citrate
      synthase (CS) were measured in mitochondria isolated from rabbit Type I and Type
      IIb muscles and in whole muscle homogenates, representing the various fiber
      types, from rats. In isolated rabbit muscle mitochondria, NAD-IDH had
      significantly higher (1.6 x ) activity in white muscle while forward NADP-IDH,
      forward and reverse H+-Thase, and CS all had significantly higher (1.2-1.6 x )
      activities in red muscle. There was no difference in reverse NADP-IDH between
      fiber types. Similarly, in rat whole muscle enzyme activities normalized to CS,
      NAD-IDH had significantly higher activity in fast-twitch glycolytic (FG) fibers,
      while forward NADP-IDH and forward H+-Thase had significantly higher activities
      in slow-twitch oxidative (SO) fibers. These results suggest that differences in
      the activities of the substrate cycle enzymes between skeletal muscle fiber types
      could contribute to differences in respiratory control due to differential
      cycling rates and/or loci of control.

PMID- 9518623
TI  - The effects of simulated ischemia on the levels of adenosine and its metabolites
      in slices of cerebellum, superior colliculus and hippocampus in the guinea pig-in
      vitro study.
AB  - The purpose of this present study is to clarify adenosine (ADO) metabolism in
      guinea pig brain slices during simulated ischemia. In slice preparations after
      decapitation, ADO levels were lowest in slices of the cerebellum (1.2 nmol/mg
      protein), followed by the superior colliculus (3.4) and highest in the
      hippocampus (6.4), and the combined concentrations of inosine (Ino) and
      hypoxanthine (HX) were highest in the cerebellum (5.5), followed by the superior
      colliculus (3.5) and the hippocampus (1.5). After preincubation with standard
      medium with oxygen and glucose for 30 min, total ADO levels (tissue ADO plus ADO
      lost into medium during incubation) decreased to 0.3 in the cerebellum, to 1.3 in
      the superior colliculus and to 2. 9 in the hippocampus. On the other hand, levels
      of total Ino and HX increased to 21.1 in the cerebellum, to 14.3 in the
      hippocampus and to 12.0 in the superior colliculus. To investigate the effect of
      simulated ischemia on ADO metabolism, preincubated slices were exposed for 10 min
      in medium deprived of oxygen and glucose. The increases of ADO content after 10
      min ischemia were 0.2 in the cerebellum, 1.0 in the superior colliculus and 1.3
      in the hippocampus. In contrast, the increases of both Ino and HX concentrations
      were 2.9 in the cerebellum, 2.2 in the superior colliculus and 1.4 in the
      hippocampus. The total amount of the increase in ADO, Ino and HX was
      approximately 3 in all three regions. These results indicate that there are
      significant differences in the metabolic rate to degrade ADO into Ino and HX in
      various areas of brain possibly due to differences in adenosine deaminase
      activity in those areas.

PMID- 9518624
TI  - The interaction of lung annexin I with phospholipid monolayers at the air/water
      interface.
AB  - Lung annexin I (LAI), a calcium-ion-dependent phospholipid-binding protein, has
      been shown earlier to cause aggregation and fusion of bilayered vesicles
      containing phospholipids found in lung surfactant, and to be a very likely factor
      in the assembly of lung surfactant into the lamellar bodies stored in the Type II
      cell. In this study, we have measured the accumulation of LAI into spread
      monolayers of some major lipid components of lung surfactant, dipalmitoyl
      phosphatidylcholine (DPPC), dipalmitoyl-phosphatidylglycerol (DPPG), palmitoyl
      oleyoyl-phosphatidylglycerol (POPG), and selected mixtures, as a function of
      calcium-ion concentration and surface concentration (degree of packing) of the
      phospholipid monolayer. The ability of LAI to significantly penetrate such
      monolayers was calcium-ion-dependent and only occurred in the presence of DPPG or
      POPG. The relative extent of penetration into DPPG and POPG was directly related
      to the available free area in the monolayer, penetration being greater with POPG.
      Fluorescence microscopy measurements revealed that DPPC mixed with either DPPG or
      POPG caused a change in surface phase behavior in a manner believed to be related
      to certain types of bilayer fusion. A chemical breakdown product of LAI, LAI-bp,
      previously found not to cause aggregation and fusion of bilayers, did not exhibit
      comparable monolayer penetration or surface phase separation to LAI.

PMID- 9518626
TI  - Metabolic mapping of the brain in pregnant, parturient and lactating rats using
      fos immunohistochemistry.
AB  - The present study was designed to investigate Fos-positive neurons of the female
      rat brain at various reproductive states in order to analyze the metabolic map
      connected with pregnancy, parturition and lactation. The number of Fos-positive
      neurons in each brain nucleus was analyzed with a quantitative
      immunohistochemical method in virgin, pregnant, parturient, lactating and
      arrested lactating rats. In parturient rats, a significant number of Fos-positive
      neurons was observed as compared to virgin or pregnant females in the following
      brain regions; the bed nucleus of the stria terminalis (BST), lateral septal
      nucleus (LS), medial preoptic area (MPA), periventricular hypothalamic nucleus
      (Pe), parvocellular paraventricular hypothalamic nucleus (PaPVN), magnocellular
      paraventricular hypothalamic nucleus (MaPVN), supraoptic nucleus (SON),
      paraventricular thalamic nucleus (PV), anterior hypothalamic area (AHA), lateral
      hypothalamic area (LH), amygdaloid nucleus (AM), supramammillary nucleus (SuM),
      substantia nigra (SN), central grey (CG), microcellular tegmental nucleus (MiTg),
      subparafascicular thalamic nucleus (SPF), posterior hypothalamic area (PH),
      dorsal raphe nucleus (DR), locus coeruleus (LC), dorsal parabrachial nucleus
      (DPB), nucleus of solitary tract (Sol), and ventrolateral medulla (VLM).
      Significant differences were found in the number of Fos-positive neurons between
      parturient and lactating females, although localization of Fos-positive neurons
      in lactating females was quite similar to parturient ones. Between parturient and
      lactating rats: (1) In the MPA, PaPVN, AHA, arcuate hypothalamic nucleus (Arc),
      ventromedial hypothalamic nucleus (VMH), MLT, and Ge, the number of Fos-positive
      neurons of lactating females were significantly higher than those of parturient
      ones; (2) In the LS, Pe, PV, LH, AM, SuM, CG, MiTg, SPF, PH, DR, LC, and VLM,
      there was no significant differences in the number of Fos-positive neurons; (3)
      In the BST, MaPVN, SON, SN, DPB and Sol, the number of Fos-positive neurons of
      lactating rats were significantly lower than those of parturient ones. These
      different patterns of Fos expression among many brain regions may be owing to the
      functional differences in each region. Fos expression in lactating rats was
      apparently induced by suckling stimulation because the removal of their litters
      immediately after parturition completely eliminated expression of Fos protein in
      each nucleus. These results suggest that the localization of Fos-positive neurons
      in a number of neural populations throughout the brain may be revealing the
      neural circuits in response to parturition or lactation.

PMID- 9518627
TI  - The distribution of neurons in the substantia nigra pars reticulata with input
      from the motor, premotor and prefrontal areas of the cerebral cortex in monkeys.
AB  - We investigated the distribution of neurons in the substantia nigra pars
      reticulata (SNr) which received cortical input. The activities of single SNr
      neurons were studied extracellulary in awake monkeys. SNr neurons showed
      excitatory and/or inhibitory responses to cortical stimulation. These responses
      were considered to be mediated by the subthalamic nucleus and striatum,
      respectively. The neurons receiving inhibitory input from the motor, premotor and
      supplementary motor areas (Motor-related cortical areas) were located in the
      lateral part of the SNr, whereas those with input from the medial, dorsal and
      orbital areas of the prefrontal cortex (PFmdo) were frequently found in the
      rostro-medial part of this nucleus. SNr neurons with inhibitory input from the
      ventral periprincipal area (PSv) were mainly distributed in the intermedio
      lateral portion, with some degree of overlap with input from other cortical
      areas. The distribution of the excitatory input was almost similar to that of
      inhibitory one, but the excitatory input from the PSv was much stronger than that
      from the PFmdo. Some SNr neurons receiving cortical input were proved to project
      to the thalamus. Our results support the existence of several parallel
      organization of the cortico-basal ganglia loop circuits [G.E. Alexander, M.R.
      DeLong, P.L. Strick, Parallel organization of functionally segregated circuits
      linking basal ganglia and cortex, Ann. Rev. Neurosci., 9, 1986, pp. 357-381.],
      but interaction between the loops can not be ignored.

PMID- 9518628
TI  - Suppression of glomus cell K+ conductance by 4-aminopyridine is not related to
      [Ca2+]i, dopamine release and chemosensory discharge from carotid body.
AB  - The hypothesis that suppression of O2-sensitive K+ current is the initial event
      in hypoxic chemotransduction in the carotid body glomus cells was tested by using
      4-aminopyridine (4-AP), a known suppressant of K+ current, on intracellular
      [Ca2+]i, dopamine secretion and chemosensory discharge in cat carotid body (CB).
      In vitro experiments were performed with superfused-perfused cat CBs, measuring
      chemosensory discharge, monitoring dopamine release by microsensors without and
      with 4-AP (0.2, 1.0 and 2.0 mM in CO2-HCO3- buffer) and recording [Ca2+]i by
      ratio fluorometry in isolated cat and rat glomus cells. 4-AP decreased the
      chemosensory activities in normoxia but remained the same in hypoxia and in flow
      interruption. It decreased the tissue dopamine release in normoxia, and showed an
      additional inhibition with hypoxia. Also, 4-AP did not evoke any rise in [Ca2+]i
      in glomus cells either during normoxia and hypoxia, although hypoxia stimulated
      it. Thus, the lack of stimulatory effect on chemosensory discharge, inhibition of
      dopamine release and unaltered [Ca2+]i by 4-AP are not consistent with the
      implied meaning of the suppressant effect on K+ current of glomus cells.

PMID- 9518629
TI  - pH dependence of the function of sodium ion extrusion systems in Escherichia
      coli.
AB  - Escherichia coli has three systems for sodium ion extrusion, NhaA, NhaB and ChaA.
      In this study, we examined the effect of pH on the function of these transporters
      using mutants having one of them, and found that (1) a mutant having NhaB
      excreted sodium ions at pH 7.5 but not at pH 8.5, (2) the efflux of sodium ions
      from mutant cells having ChaA was observed at both pH 7.5 and 8.5, but the
      activity was lower at pH 7.5, and (3) sodium ions were excreted from mutant cells
      having NhaA at pH 6.5 to 8.5. The extrusion activity of cells having NhaA was
      higher than that of cells having NhaB or ChaA. These results indicate that NhaB
      functions at a pH below 8, and ChaA extrudes sodium ions mainly at an alkaline pH
      above 8. It was also suggested that the activity of NhaB and ChaA is not enough
      to maintain a low level of internal sodium ions when the external concentration
      of sodium ions is high, and NhaA is induced within a wide range of medium pH
      under such conditions.

PMID- 9518630
TI  - Complete inhibition of Na+, K+, Cl- cotransport in Madin-Darby canine kidney
      cells by PMA-sensitive protein kinase.
AB  - This study examines the involvement of hormones and neuromediators in the
      regulation of Na+, K+, Cl- cotransport in renal epithelial cells using Madin
      Darby canine kidney cells with low transepithelial electrical resistance (194+/
      47 Omega/cm2). In this cell line, Na+, K+, Cl- cotransport measured as bumetanide
      sensitive 86Rb influx was inhibited up to 50-60% with agonists of P2
      purinoceptors (ATP approximately ADP>UTP>AMP), slightly (15-30%) increased by
      activators of cAMP signaling (forskolin, 8-Br-cAMP) and was insensitive to
      activators of cGMP signaling (8-Br-cGMP, nitroprusside), EGF, angiotensin II,
      bradykinin, methacholine, propranolol, vasopressin, adenosine, dopamine and
      histamine. Thirty min of preincubation of MDCK cells with 0.1 microM PMA
      completely blocked the activity of Na+, K+, Cl- cotransport whereas down
      regulation of this enzyme by 24 h of preincubation with 1 microM PMA activated
      Na+, K+, Cl- cotransport by 60% and abolished the effect of short-term treatment
      with PMA. Regulation of Na+, K+, Cl- cotransport by ATP was insensitive to down
      regulation of PMA-sensitive isoforms of protein kinase C. In addition, an
      inhibitor of protein kinase activity, staurosporine, abolished the effect of 0.1
      microM PMA but did not change inhibition of this carrier by ATP. Thus, these
      results show for the first time that P2-purinoceptors and PMA-sensitive isoforms
      of protein kinase C play a key role in the regulation of Na+, K+, Cl- cotransport
      in MDCK cells. These results also show that neither PMA- nor staurosporine
      sensitive forms of protein kinase are involved in the inhibition of Na+, K+, Cl-
      cotransport by activators of P2-purinoceptors.

PMID- 9518631
TI  - Water version of the radial-arm maze: learning in three inbred strains of mice.
AB  - The conventional land radial-arm maze has several disadvantages, including
      requiring a complicated automated apparatus, the elimination of odors as cues,
      and the use of food deprivation. We have created a water version of the maze,
      based on the principles of the land version, which maintains the advantages and
      excludes some of the disadvantages. In our maze, BXSB and C57BL/6 mice
      significantly reduced the number of working and reference memory errors committed
      over sessions, while NZB mice did not. For each strain, as the working memory
      'load' increased during a session, the number of errors increased. However, with
      practice the BXSB and C57BL/6 strains were able to handle this memory load more
      effectively. Mice were able to learn the maze without extensive adaptation,
      training, or testing and they did not exhibit 'chaining'. This maze can also be
      considered to be an example of a water win-shift task that mice can easily learn.
      Therefore, the water version of the radial-arm maze can be a simple and useful
      tool for studying rodent learning and memory.

PMID- 9518632
TI  - Maximal densities of mu, delta, and kappa receptors are differentially altered by
      focal cerebral ischaemia in the mouse.
AB  - Though opioids are known to have neuroprotective properties, little information
      is available on the functional state of opioidergic receptors following focal
      cerebral ischaemia. The present study investigated the evolution of the Bmax and
      Kd for [3H]DAMGO, [3H]DADLE, and [3H]U69,593, respectively, for the mu, delta,
      and kappa opioidergic receptors after permanent focal cerebral ischaemia in mice.
      While the various Kd were unchanged, mu and delta Bmax values were precociously
      decreased in frontoparietal cortices, earlier than kappa receptors, reflecting
      infarct extension with time. The Bmax values for mu and delta receptors were also
      altered in non-infarcted tissues, such as tissues at risk (e.g., temporal
      auditory cortex) and exofocal (e.g., contralateral and non-infarcted) cortices.
      These results suggest that, in non-infarcted areas, the observed changes reflect
      functional modifications to focal ischaemia.

PMID- 9518633
TI  - Infarct tolerance against temporary focal ischemia following spreading depression
      in rat brain.
AB  - A rat model of ischemic tolerance is useful for studying the intrinsic cellular
      mechanism of resistance to cerebral ischemia. Many types of preconditioning in
      the brain have been reported to induce ischemic tolerance; however, evaluation of
      their neuroprotective effect is primarily limited to differences in counts of
      surviving cells. A lesser but still large number of neurons die in the neocortex
      after global ischemia following ischemic tolerance. This study addressed the
      issue of whether any type of preconditioning could elicit a tolerance that
      limited the size of cerebral infarct against temporary focal ischemia. Cortical
      spreading depression was induced for a prolonged period and, after various
      intervals, the stress of temporary focal ischemia was evaluated in rats. Ten
      groups of male rats (n=8 each) were studied. In the first group, temporary focal
      ischemia was induced by occlusion of three vessels (bilateral carotid arteries
      and left middle cerebral artery, MCA) for 2 h (control). In the second to seventh
      groups, cortical spreading depression was generated by continuously infusing 4 M
      potassium chloride (KCl)(1.0 microliter l/h for 2 days) into the left neocortex
      via an osmotic pump. On days 6, 9, 12, 15, 21 and 24 (day 0=day of pump removal),
      temporary focal ischemia was induced in one of these groups. In the other three
      groups, saline was infused instead of KCl, and on day 6, 12 or 21, temporary
      focal ischemia was induced. All rats were sacrificed 2 days after the ischemia
      and the infarct volume was analyzed using TTC staining of brain slices. In a
      separate group of animals, regional cerebral blood flow (rCBF) at the periinfarct
      area (penumbra) was monitored before and during the ischemia with a laser-Doppler
      flowmetry (LDF) system on day 12 following saline (n=5) or KCl infusion (n=5) for
      48 h. To obtain the absolute rCBF value before ischemia following saline (n=5) or
      KCl infusion (n=5), hydrogen clearance was examined in the same cortex under the
      same anesthesia. The cerebral infarct volume was gradually reduced as the
      interval between the induction of the spreading depression and the induction of
      temporary focal ischemia was extended. There was a significant reduction in
      infarct size between the control and the groups in which ischemia was induced on
      day 12 or 15. There was no significant difference in the preischemic or
      intraischemic rCBF between the saline and KCl-infused groups. The preconditioning
      method was demonstrated to limit the size of cerebral infarct after temporary
      focal cerebral ischemia; tolerance for cerebral infarct developed after an
      extended interval following a long period of spreading depression.

PMID- 9518634
TI  - Membrane dynamics in the intact PM2 phage and its host cells as monitored by
      T1rho(H).
AB  - Temperature dependence of the spin-lattice relaxation time of proton in the
      rotating frame (T1rho(H)) was examined for the membranes of the intact PM2 phage,
      its host bacterial cells, and the phospholipids extracted from the cells. The
      relevant motions of the phospholipid molecules in all lipid membranes were found
      in the fast-motional regime (tauc < 1.7 x 10(-6) s) in the temperature range from
      0 to 34 degrees C. The motions responsible for the relaxation in the intact
      biomembranes are more suppressed than those of the extracted phospholipid
      bilayers, suggesting that the lipid-protein interactions induce slow motions of
      the phospholipids in the membrane. Especially, the membrane of the intact PM2
      phage showed a cooperative change in the motional state, being consistent with
      the reported change in the phosphorus chemical shift anisotropies of DNA and
      phospholipids of the phage particle.

PMID- 9518635
TI  - Cyclic AMP antagonizes adenosine-induced inhibition of ganglionic transmission.
AB  - The mechanism of adenosine-induced inhibition of ganglionic transmission was
      investigated in the isolated superior cervical ganglion (SCG) of the rat. The
      inhibitory effect of adenosine on the postganglionic compound action potential
      (CAP) was antagonized by pretreatment of ganglia with forskolin, isoproterenol
      (IPNE), arginine vasopressin (AVP), or papaverine, all of which are known to
      increase tissue cAMP level by different mechanisms. Furthermore, pretreatment of
      ganglia with the adenylate cyclase inhibitor SQ 22, 536, or the phosphodiesterase
      activator imidazole reversed the effects of IPNE and forskolin. Pretreatment with
      8-bromo-cAMP, resulted in a marked antagonism of the adenosine-induced
      inhibition. By themselves, none of these drugs had any significant effect on the
      CAP. Adenosine slightly but significantly decreased the basal level of cAMP in
      untreated ganglia. Formation of cAMP induced by IPNE was markedly reduced by
      adenosine. This was largely reversed in the presence of the adenosine A1 receptor
      antagonist 8-cyclopentyl-1, 3-dipropylxanthine (DPCPX) but not the A2 receptor
      antagonist 3, 7-dimethyl-1-propargylxanthine (DPMX). We conclude that the
      inhibition of ganglionic transmission by adenosine involves reduction of cAMP
      formation through activation of A1 receptors.

PMID- 9518636
TI  - Overexpression of a minor component of myelin basic protein isoform (17.2 kDa)
      can restore myelinogenesis in transgenic shiverer mice.
AB  - Shiverer (shi) mice, which are neurologically mutant, lack a large portion of the
      gene for the myelin basic proteins (MBPs), have virtually no myelin in their
      central nervous system (CNS), and shiver, undergo seizures, and die early. At
      least five types of MBPs (21.5, 18.5, 17.3, 17.2 and 14.0 kDa) are known to be
      generated through alternative splicing from a single MBP gene. We have produced
      transgenic shi mice carrying a cDNA encoding mouse 14-kDa MBP isoform, the most
      abundant form of MBPs, under control of a mouse MBP gene promoter, and showed
      that expression of the 14-kDa MBP can restore CNS myelination. To test whether
      the 17.2-kDa MBP isoform, one of the minor components of MBPs, can also elicit
      myelination in homozygous shi mutants, we produced seven independent transgenic
      shi mice carrying cDNA encoding the mouse 17.2-kDa MBP isoform, and the
      transcription of which was driven by a mouse MBP gene promoter. The axons in the
      cerebellum of one transgenic line, which exhibited the highest expression of
      transgene-derived mRNA ( approximately 50% of the level of total MBP mRNA in the
      normal mouse brain), were myelinated. This mouse exhibited nearly normal
      behavior. These findings indicate that the 17.2-kDa MBP isoform, even when the
      only 17.2-kDa MBP isoform is present, has the ability to elicit CNS myelination
      in transgenic shi mice. This transgenic strategy will be useful for elucidating
      the role of each type of MBP isoform in CNS myelinogenesis.

PMID- 9518637
TI  - Ontogeny of basolateral membrane sodium-hydrogen exchange (NHE) activity and mRNA
      expression of NHE-1 and NHE-4 in rat kidney and jejunum.
AB  - Na+/H+ exchange (NHE) activity varies with ontogenic state in rat intestinal
      basolateral membrane vesicles (BLMV). The current investigation sought to
      determine if these observations are due to differential expression of BLM NHE
      isoforms, NHE-1 and NHE-4. In rat kidney, BLMV sodium uptake levels were similar
      in 2, 3 and 6 week rats (13.28+/-0.68, 14.03+/-0.84, and 11.71+/-0.66 nmol Na+/mg
      protein/30 s, respectively), and lower in adults (5.53+/-0.24) (n=4; p<0.001
      between 2 week rats and adults, and between 3 week rats and adults; p<0.01
      between 6 week rats and adults). In rat jejunum, BLMV uptake was highest in
      adults (13.07+/-0.86 nmol Na+/mg protein/30 s), and decreased in 6, 3, and 2 week
      rats (4.48+/-0.75, 2.94+/-0.68, and 1.59+/-0.58, respectively) (n=4; p<0.001
      between all groups and adults). Control immunoblot experiments with NHE-3
      antiserum showed that BLMV preps were not contaminated with significant amounts
      of this brush-border membrane specific protein. Northern blots with isoform
      specific probes showed highest renal NHE-1 hybridization intensities in 2 and 3
      week rats (11.00+/-0.25 and 12.07+/-0.16 phosphorimage units, respectively), and
      lower intensities in 6 week and adult animals (4.30+/-0.95, and 4.40+/-1.40,
      respectively) (n=4; p<0.01 between 2 week animals and 6 week and adult animals,
      and between 3 week animals and 6 week and adult animals). NHE-1 probes in the
      intestine showed no hybridization intensity differences between groups: 2 week
      7.09+/-1.10, 3 week-5.39+/-0.56, 6 week-8. 24+/-1.57, and adult-8.99+/-2.20
      (n=3). NHE-4 specific probes in the kidney showed hybridization intensity levels
      of 9.22+/-0.35 in 2 week animals, 12.12+/-1.26 in 3 week animals, 5.63+/-0.81 in
      6 week animals, and 3.52+/-0.57 in adults (n=4; p<0.05 between 2 week and adults;
      p<0.01 between 3 week and 6 week animals, and between 3 week and adults). No NHE
      4 message was detected in rat jejunum by Northern blot analysis or by reverse
      transcriptase-PCR. These results suggest that ontogenic NHE activity at the
      jejunal BLM is not related to differential expression of NHE-1, while NHE
      activity at the renal BLM may in part be related to differential ontogenic
      expression of NHE-1 and NHE-4.

PMID- 9518638
TI  - Developmental expression of acetyl- and butyrylcholinesterase in the rat: enzyme
      and mRNA levels in embryonic dorsal root ganglia.
AB  - Dorsal root ganglia (DRG) in the adult rat contain acetylcholinesterase (AChE)
      and butyrylcholinesterase (BChE), enzymes implicated in neural morphogenesis. We
      used quantitative histochemistry, reverse transcription-PCR (RT-PCR), and in situ
      hybridization histochemistry to study cholinesterase expression during
      embryogenesis. Longitudinal sections of rat embryos, embryonic day 9 (E9), E11
      E17, and E19, were studied by video microscopy of the stained enzyme reaction
      products. Both enzymes were detectable in the early DRG (E11-E12), with BChE
      being most prominent. There was a spatiotemporal change in expression of each
      cholinesterase within the DRG. From E13 on, AChE expression predominated,
      especially in the neuronal cell bodies, while BChE was more highly expressed in
      the surrounding neuropil and the ganglionic roots. This distribution resembled
      the pattern in adult DRG. AChE mRNA levels, as determined by RT-PCR from DRG
      collected at days E12-E17, and E19, varied in parallel with the intensity of
      enzyme stain in the DRG. Overall, these results demonstrate temporally regulated
      ganglionic expression of cholinesterases, which may be important in the
      development of the sensory nervous system.

PMID- 9518639
TI  - Induction of infarct tolerance by platelet-derived growth factor against
      reversible focal ischemia.
AB  - Nerve growth factor, brain-derived neurotrophic factor, and other neurotrophic
      factors have been reported to have neuroprotective effects against global
      ischemia. To investigate whether the homodimer of platelet-derived growth factor
      B-chain (PDGF-BB) can protect neurons against focal temporary ischemia, PDGF-BB
      was administered to the rat brain for a prolonged period prior to, during, and
      after ischemia, since PDGF-BB protected rat neurons from global ischemia in our
      previous study. A total of 82 male Sprague-Dawley rats were used. Recombinant
      PDGF-BB, or saline was administered into the left neocortex via an implanted
      osmotic pump for 3 days (1.2 microg in total), 7 days (2 microgram or 4 microgram
      in total), or 14 days (4 microgram in total) pre-ischemia and 2 days post
      ischemia. In an additional group, PDGF-BB (4 microgram in total) was administered
      for 14 days by osmotic pump and focal ischemia was induced after an additional 7
      day interval following removal of the pump. Focal temporary ischemia was induced
      in the left MCA territory by bilateral CCA and MCA occlusion for 2 h. All rats
      were sacrificed 2 days after ischemia and the volume of cerebral infarct was
      analyzed using TTC staining. In a separate set of animals, regional cerebral
      blood flow (rCBF) was monitored by the hydrogen clearance method and laser
      Doppler flowmetry (LDF) of the neocortex after 14 days of intracerebral
      administration of PDGF-BB or saline. In the group receiving PDGF-BB (4 microgram
      in total) for 7 or 14 days pre-ischemia, there was a significant reduction of
      neocortical infarction compared to that in the control or saline-infused group.
      The size of cerebral infarct was smallest in the group that received PDGF-BB for
      14 days, when ischemia was induced 7 days after removal of the pump. Regarding
      rCBF measurement, there were no significant differences in groups receiving PDGF
      BB or saline infusion for 14 days. The potent neuroprotective effect of PDGF-BB
      on global ischemia was also demonstrated in the focal ischemia model. However,
      prolonged intracerebral infusion for 7 to 14 days was necessary to achieve a
      significant reduction of infarct volume. Neuroprotection was not due to increased
      collateral flow during ischemia.

PMID- 9518640
TI  - ETA and ETB receptor antagonists synergistically increase extracellular
      endothelin-1 levels in primary rat astrocyte cultures.
AB  - Astrocytes produce and bind endothelins (ETs), suggesting that these cells have
      ET autoregulatory and eliminatory functions. To further investigate these
      functions in primary rat astrocytes, ET-1 levels in the cell culture media
      (RIA/HPLC) and intracellular content of ET-1 mRNA (RT PCR) were measured under
      basal and stimulated (thrombin, 2.2 U/ml) conditions in the presence and absence
      of ETA and ETB selective antagonists (BQ123 or LU135252, and BQ788,
      respectively). Neither basal nor stimulated ET-1 levels in astrocyte media were
      influenced by ETA or ETB antagonists alone, but were significantly increased by a
      combination of both. ir ET-3 levels were not affected by antagonist treatment.
      Exogenous ET-1, added to the cultures, was rapidly cleared from the supernatant;
      this clearance was markedly inhibited by a combination of BQ123 and BQ788. ET-1
      mRNA levels were not altered by any treatment. To conclude, in primary rat
      astrocyte cultures, extracellular ET-1 is cleared by binding to ET-receptors,
      apparently involving both, ETA and ETB sites. Thus, a blockade of the astrocytic
      ET eliminatory function as a consequence of the in vivo application of non
      selective ET receptor antagonists may lead to increased extracellular ET levels
      in the brain.

PMID- 9518642
TI  - Levels of trkA and BDNF mRNA, but not NGF mRNA, fluctuate across the estrous
      cycle and increase in response to acute hormone replacement.
AB  - Recent studies suggest that hormone replacement therapy can help to reduce the
      risk and severity of Alzheimer's-related dementia in postmenopausal women. We
      have hypothesized that these effects are due, in part, to the ability for
      estrogen and progesterone to enhance hippocampal function, as well as the
      functional status of cholinergic projections to the hippocampus and cortex, by
      influencing the expression of specific neurotrophins and neurotrophin receptors.
      In the present study, quantitative in situ hybridization techniques were used to
      determine whether the levels of trkA mRNA in the basal forebrain, and nerve
      growth factor (NGF) mRNA and brain-derived neurotrophic factor (BDNF) mRNA in the
      hippocampus, are significantly affected by physiological changes in circulating
      gonadal steroids. Gonadally intact animals were sacrificed at different stages of
      the estrous cycle and ovariectomized animals were sacrificed at different times
      following the administration of either estrogen or estrogen plus progesterone. In
      gonadally intact animals, significant fluctuations in the levels of trkA mRNA in
      the medial septum (MS), and BDNF mRNA in regions CA1 and CA3/4 of the
      hippocampus, were detected across the estrous cycle. In animals that received
      hormone replacement, a significant increase (30.4%) in trkA mRNA was detected in
      the MS of animals sacrificed 24 h following estrogen administration. Levels of
      trkA mRNA in the MS declined to control levels over the next 48 h; however, a
      single injection of progesterone administered 48 h after estradiol appeared to
      prevent any further decline in trkA mRNA over the next 24 h. In addition,
      significant increases in BDNF mRNA were detected in the dentate granule cell
      layer (73.4%), region CA1 (28. 1%), and region CA3/4 (76.9%) of animals
      sacrificed 53 h after receiving estrogen and 5 h after receiving progesterone. No
      significant changes in trkA mRNA were detected in the nucleus basalis
      magnocellularis, and no significant changes in NGF mRNA were detected in the
      hippocampus. These data demonstrate that levels of trkA mRNA in the MS, and BDNF
      mRNA in the hippocampus, are affected by physiological changes in the levels of
      circulating gonadal steroids and are elevated in response to acute hormone
      replacement. The relevance of these effects to the ability for estrogen
      replacement to enhance cholinergic activity and hippocampal function, and thereby
      reduce the risk and severity of Alzheimer's-related dementia in postmenopausal
      women, is discussed.

PMID- 9518641
TI  - The novel benzodiazepine inverse agonist RO19-4603 antagonizes ethanol motivated
      behaviors: neuropharmacological studies.
AB  - The novel imidazothienodiazepine inverse agonist RO19-4603 has been reported to
      attenuate EtOH intake in home cage drinking tests for at least 24 h post-drug
      administration after systemic administration. In the present study, selectively
      bred alcohol-preferring (P) rats were trained under a concurrent (FR4-FR4)
      operant schedule to press one lever for EtOH (10% v/v) and another lever for
      saccharin (0.05% or 0.75% g/v), then dose-response and timecourse effects of RO19
      4603 were evaluated. Systemic RO19-4603 injections (0.0045-0.3 mg/kg; i.p.)
      profoundly reduced EtOH responding by as much as 97% of vehicle control on day 1.
      No effects were seen on saccharin responding except with the highest dose level
      (0.3 mg/kg). In a second experiment, microinjections of RO19-4603 (2-100 ng)
      directly into the nucleus accumbens (NA) suppressed EtOH responding on day 1 by
      as much as 53% of control: Control injections dorsal to the NA or ventral
      tegmental area did not significantly alter EtOH or saccharin responding. On day
      2, rats in both experiments received no RO19-4603 treatments; however, all 7 of
      the i.p. doses, and all 3 of the intra-NA infusions continued to significantly
      suppress EtOH responding by 43-85% of vehicle control levels. In addition, i.p.
      injections of RO19-4603 produced a dose-dependent decrease in the slope of the
      cumulative record for EtOH responding, while concomitantly producing a dose
      dependent increase in the slope for saccharin responding. RO19-4603's actions
      appear to be mediated via recognition sites at GABAA-BDZ receptors which regulate
      EtOH reinforcement, and not via mechanisms regulating ingestive behaviors. Based
      on recent in situ hybridization studies in our laboratory, we hypothesize that
      occupation of alpha4 containing GABAA diazepam insensitive (DI) receptors in the
      NA, may mediate in part, the RO19-4603 suppression of EtOH responding in EtOH
      seeking P rats.

PMID- 9518643
TI  - Lateral diffusion of the total polar lipids from Thermoplasma acidophilum in
      multilamellar liposomes.
AB  - 31P NMR lineshapes of multilamellar liposomes composed mostly of a bilayer
      spanning tetraether lipid are consistent with rapid axially symmetric motion
      about the bilayer normal. The residual chemical shift anisotropy of 36 ppm is
      comparable to that seen for diacylphosphatidylglycerol systems and suggests
      comparable headgroup motion. The lateral diffusion rates for Thermoplasma
      acidophilum total polar lipids in mutilamellar liposomes was measured by two
      dimensional exchange NMR as a function of temperature. At 55 degrees C, near the
      growth temperature, the rate of lateral diffusion, DL, is comparable to that of
      diester phospholipids in the Lalpha liquid crystalline phase, having a value of 2
      x 10(-8) cm2/s. DL decreases with temperature reaching a value of 8-6 x 10(-9)
      cm2/s at 30 degrees C. The activation energy Ea for lateral diffusion is
      estimated to be 10 kcal/mol (approximately 42 kJ/mol). The lateral diffusion
      rates indicate that the tetraether liposomes have a membrane viscosity at 30
      degrees C which is considerably higher than that of diester phospholipids in the
      liquid crystalline phase.

PMID- 9518645
TI  - Peptide-liposome association. A critical examination with mastoparan-X.
AB  - Mastoparan-X, a wasp venom factor, is a membrane active peptide whose binding to
      lipid vesicles is of basic interest towards an analysis of its functions.
      Titration of aqueous peptide solutions with liposomes allows the determination of
      the association isotherm, i.e. a plot of bound peptide per lipid versus the free
      peptide concentration. We have scrutinised the various steps in the evaluation
      procedure, considering circular dichroism as well as fluorescence intensity as
      possible signals for the binding process. First of all the measured data had to
      be corrected for light scattering effects which may otherwise appreciably falsify
      the final results. Uncertainties due to inherent difficulties regarding the
      reproducibility of lipid preparations and inevitable titration errors have to be
      considered. The consequences of these errors for the quantitative analysis of the
      titration curves were investigated. The plotted curves can be reasonably well
      fitted by a functional relationship derived from a Gouy-Chapman model approach
      that assumes a partitioning of monomeric peptide. The two relevant parameters,
      partition coefficient and effective charge number, and their error ranges have
      been determined for mastoparan-X and a series of phosphatidylcholine vesicle
      sizes and various ionic strengths. These findings show that the applied analysis
      implies a sufficient basis for calculations of the amount of lipid bound peptide
      in practice. However, the possible existence of peptide aggregates cannot
      generally be excluded from a formal monomer associated curve fit as indicated by
      computer simulations.

PMID- 9518646
TI  - Viscerosomatic interactions in the thalamic ventral posterolateral nucleus (VPL)
      of the squirrel monkey.
AB  - In anesthetized squirrel monkeys single cell recordings were performed using
      tungsten microelectrodes. The responses of 29 viscerosomatoceptive and
      somatoceptive VPL neurons to noxious distension of the urinary bladder, the lower
      esophagus and the distal colon and to innocuous and noxious somatic stimuli were
      assessed when these stimuli were presented separately or together. Neuronal
      responses were defined as additive or interactive depending on the relative
      changes in responses to individual somatic or visceral stimuli, and on their
      responses during conditioning (somatic and visceral stimuli applied
      concurrently). In 13 neurons interactions between the somatosensory and visceral
      inputs could be demonstrated. The dominant interactive effect was inhibition,
      although facilitatory effects were seen as well (2 of 13). The magnitude or
      direction of the interactions seemed independent of the location of the somatic
      and visceral receptive fields. The mean population response of the neurons
      showing interactions was 4.66 spikes/s to somatic stimulation, and 0.07 spikes/s
      to visceral stimulation. During conditioning the mean interactive effect was -62%
      of the calculated additive effect. This implies that overall the somatic
      responses are halved during a coincident visceral stimulus. In a subgroup of the
      VPL neurons, which were classified as pure somatic responsive (n=14) due to their
      unresponsiveness during visceral stimulation alone, a third (n=5) still exhibited
      visceral convergence during conditioning. The latter neurons, therefore, receive
      visceral inputs, which function in a purely interactive (modulatory) manner. It
      is concluded that part of the described effects is due to competition (cross
      modality suppression) between the visceral and somatic inputs. We further
      conclude that the suppression of somatic information by noxious visceral stimuli
      may contribute to a more effective processing of the discriminatory aspects of
      nociceptive visceral information previously demonstrated in VPL.

PMID- 9518644
TI  - Expression of c-fos and hsp70 mRNA in neonatal rat cerebrocortical slices during
      NMDA-induced necrosis and apoptosis.
AB  - Respiring neonatal rat cerebrocortical slices were exposed for 30 min to toxic
      concentrations of N-methyl-D-aspartate (NMDA; 100 microM, 500 microM and 1000
      microM). In situ hybridization was used to study c-fos and hsp70 mRNA before,
      during, and for 8 h after NMDA exposure. Cell swelling and nuclear morphology
      were assessed using Cresyl violet (Nissl) staining. Possible evidence for
      apoptosis was examined using in situ terminal transferase d-UTP nick-end labeling
      (TUNEL) staining and agarose-gel electrophoresis of extracted slice DNA. After
      NMDA administration c-fos and hsp70 mRNA expression increased, with maxima
      occurring, respectively, at 1 h and 4 h after NMDA exposure. When treatment with
      dizocilpine (MK-801; 10 microM), a non-competitive NMDA antagonist, was started
      before NMDA exposures, expression of both c-fos and hsp70 mRNA was decreased to
      values near control, indicating that activation of NMDA receptors induces both
      genes. Only a minority of induced cells expressed FOS protein and no HSP70
      protein expression was seen. These apparent failures of translation might be
      related to the stress response. Histologically, 1000 microM NMDA produced
      substantial necrosis, with no evidence of apoptosis. Evidence for apoptosis was
      found at the two lower NMDA concentrations, which produced TUNEL-positive
      fragmented nuclei and faint ladder patterns in DNA electrophoresis. Dizocilpine
      pre-treatment blocked NMDA-induced necrosis and attenuated TUNEL-positive
      staining in slice parenchyma. TUNEL-positive staining with a different morphology
      was found in the injury layer, a region 50-micron thick where mechanical trauma
      was inflicted when slices were cut from brain. When slices received dizocilpine
      immediately after decapitation, TUNEL-positive staining no longer occurred in the
      injury layer, in agreement with previous cell culture studies that implicated
      NMDA receptor activation after mechanical trauma to neurons. We conclude that at
      the toxic doses studied, NMDA receptor activation results primarily in necrosis.
      However, data at low NMDA concentrations are consistent with a small amount of
      apoptosis.

PMID- 9518647
TI  - Expression, induction and regulation of the cytochrome P450 monooxygenase system
      in the rat glioma C6 cell line.
AB  - The cytochrome P450 monooxygenase system consists of NADPH-cytochrome P450
      reductase (P450 reductase) and cytochromes P450, which can catalyze the oxidation
      of a wide variety of endogenous and exogenous compounds. P450 reductase transfers
      reducing equivalents from NADPH to P450, which in turn catalyzes metabolic
      reactions. In previous studies, we have used the rat glioma C6 cell line as an in
      vitro model system and identified the presence of P450 reductase and of
      cytochrome P450 1A1, 1A2, 2A1, 2B1/2, 2C7, 2D1-5 and 2E1 by reverse transcription
      followed by polymerase chain reaction (RT-PCR). In C6 cells, the induction of
      P450 1A1 and 2B1/2 at mRNA level after BA (benzo(a)anthracene) or PB
      (phenobarbital) treatments was detected. In this study, analysis of microsomal
      preparations of glioma C6 cells was utilized to demonstrate the presence of P450
      2B and P450 reductase at the protein level. ELISAs showed that PB induced P450 2B
      proteins 12-fold. These experiments further establish that the rat glioma C6 cell
      line contains an active cytochrome P450 monooxygenase system that can be induced
      by P450 inducers. We also found that the mRNAs of P450 1A1 and 2B1/2 from glioma
      C6 cells do not bind to the oligo(dT)-based separation techniques efficiently,
      suggesting that they may have very short poly(A) tails. The half-lives of P450
      1A1 and 2B1/2 mRNA in glioma C6 cells are 1/10 and 1/3 of that in liver,
      respectively. This may partly contribute to the low expression level of P450s in
      glial cells. The induction of P450s by BA or PB did not change their mRNA half
      lives, indicating the induction may be due to transcriptional regulation. In
      summary of this study, we believe the presence of the cytochrome P450
      monooxygenase system in glial cells of the brain may be important in chemotherapy
      and carcinogenesis of brain tumors.

PMID- 9518648
TI  - Protection against blood-brain barrier disruption in focal cerebral ischemia by
      the type IV phosphodiesterase inhibitor BBB022: a quantitative study.
AB  - We examined the effect of BBB022, a type IV phosphodiesterase inhibitor, on blood
      brain barrier (BBB) integrity after transient middle cerebral artery occlusion
      (MCAo) in rats. Male Sprague-Dawley rats were anesthetized with halothane and
      subjected to 120 min of temporary MCAo by retrograde intraluminal insertion of a
      nylon suture coated with poly-L-lysine. The drug (BBB022 in saline, 1 mg kg-1 h
      1, i.v.) or vehicle (0.9% saline, 1-2 ml kg-1 h-1) was administered by infusion
      after the onset of MCAo. Four animal groups were studied: Groups A and B were
      treated by infusion of vehicle or drug over 5 h, and groups C and D over 48 h.
      Damage to the BBB was judged by extravasation of Evans blue (EB) dye, which was
      administered i.v. at 3 h after the onset of MCAo in groups A and B; and at 46 h
      in groups C and D. Fluorometric quantitation of EB was performed 1 or 2 h later
      in six brain regions. In the 5-h infusion series (group B), BBB022 decreased dye
      extravasation in the ipsilateral cortex, striatum and hemisphere (hemisphere
      mean+/-S.E.M. : 41.2+/-5.4 vs. 82.4+/-9.2 microg/g, p=0.005) compared to the
      vehicle-treated group (A). The 48-h infusion of BBB022 (group D) also decreased
      dye extravasation in the ipsilateral cortex (7.4+/-2. 5 vs. 29.0+/-8.3 microg/g,
      p=0.05), striatum (17.2+/-2.2 vs. 50. 8+/-12.1 microg/g, p=0.03) and hemisphere
      (30.7+/-4.0 vs. 93.2+/-18 microg/g, p=0.01) compared to the vehicle-treated group
      (C). BBB022 also significantly improved the neurological score at 3 and 5 h after
      MCAo (in the 5-h infusion group) and at 60 min, 24 h and 48 h (in the 48-h
      infusion group) compared to the vehicle groups. These data indicate that BBB022
      prevents ischemic damage to the BBB after focal cerebral ischemia in rats.

PMID- 9518649
TI  - The specificity and affinity of immunoliposome targeting to oral bacteria.
AB  - Immunoliposomes have been prepared using antibodies raised to an antigenic
      determinant on the cell surface of the oral bacterium Streptococcus oralis (S.
      oralis) in an investigation of their potential to reduce dental plaque. The N
      succinimidyl-S-acetylthioacetate (SATA) derivative of the antibodies were
      conjugated through the reactive m-maleimidobenzoyl-N-hydroxysuccinimide (MBS)
      derivative of dipalmitoyl-phosphatidylethanolamine (DPPE) incorporated into
      liposomes. The degree of antibody conjugation to the liposomes was controlled by
      the percentage of DPPEMBS incorporated into the liposomes. The chemical
      modification of the antibodies did not affect the ability of the antibodies to
      bind to a S. oralis biofilm. However, the affinity of the immunoliposomes for S.
      oralis was much lower than that of the free antibody. The anti-oralis antibodies
      were highly specific for S. oralis. The anti-oralis immunoliposomes showed the
      greatest affinity for S. oralis, when targeted to a range of different oral
      bacterial biofilms. The immunoliposome targeting affinity for S. oralis was
      largely unaffected by the number of antibodies conjugated to the liposomal
      surface or by the net charge of the liposomal lipid bilayer. The immunoliposomes
      showed a greater affinity for S. oralis than 'naked' (bearing no antibody)
      liposomes. However, positively charged liposomes, incorporating stearylamine,
      adsorbed to S. oralis with greater affinities than the immunoliposomes. The
      immunoliposomes appeared to be physically stable over a period of 18 months, as
      judged by particle-size measurements.

PMID- 9518650
TI  - Ischemic injury and extracellular amino acid accumulation in hippocampal area CA1
      are not dependent upon an intact septo-hippocampal pathway.
AB  - The septo-hippocampal pathway contains a major gamma-aminobutyric acid (GABA)
      projection to dendritic fields within the hippocampus. To determine the
      importance of the septo-hippocampal pathway in ischemia-induced accumulation of
      GABA and subsequent cell death in area CA1 of hippocampus, septo-hippocampal
      deafferentation of adult gerbils was performed. Electrolytic lesions were
      produced in the medial or medial plus lateral septal regions in gerbils 7 days
      prior to being subjected to 5 min forebrain ischemia. The extent of
      deafferentation of the dorsal hippocampus was determined histochemically by
      acetylcholinesterase staining. Both the medial and medial plus lateral septal
      lesions produced nearly complete loss of acetylcholinesterase staining in the
      dorsal hippocampus indicating relatively complete deafferentation. During and
      following ischemia, in vivo microdialysis was used to measure extracellular GABA
      accumulation, which reached concentrations up to 1060 +/- 143% of basal. Septo
      hippocampal deafferentation in both groups of lesioned animals failed to prevent
      the accumulation of GABA (and glutamate) induced by ischemia, indicating that
      ischemia-induced GABA accumulation in area CA1 arises principally from intrinsic
      GABAergic interneurons. Ischemic animals with medial septal lesions did not
      demonstrate neuroprotection or increased damage in the stratum pyramidale 7 days
      after reperfusion. Since the septo-hippocampal pathway provides the source of
      GABAergic disinhibition within the hippocampus, neither disinhibition nor the
      septo-hippocampal input appear to play an important role in the development of
      ischemia-induced neuronal death in the hippocampus.

PMID- 9518651
TI  - Chronic administration of aluminum-fluoride or sodium-fluoride to rats in
      drinking water: alterations in neuronal and cerebrovascular integrity.
AB  - This study describes alterations in the nervous system resulting from chronic
      administration of the fluoroaluminum complex (AlF3) or equivalent levels of
      fluoride (F) in the form of sodium-fluoride (NaF). Twenty seven adult male Long
      Evans rats were administered one of three treatments for 52 weeks: the control
      group was administered double distilled deionized drinking water (ddw). The
      aluminum-treated group received ddw with 0.5 ppm AlF3 and the NaF group received
      ddw with 2.1 ppm NaF containing the equivalent amount of F as in the AlF3 ddw.
      Tissue aluminum (Al) levels of brain, liver and kidney were assessed with the
      Direct Current Plasma (DCP) technique and its distribution assessed with Morin
      histochemistry. Histological sections of brain were stained with hematoxylin &
      eosin (H&E), Cresyl violet, Bielschowsky silver stain, or immunohistochemically
      for beta-amyloid, amyloid A, and IgM. No differences were found between the body
      weights of rats in the different treatment groups although more rats died in the
      AlF3 group than in the control group. The Al levels in samples of brain and
      kidney were higher in both the AlF3 and NaF groups relative to controls. The
      effects of the two treatments on cerebrovascular and neuronal integrity were
      qualitatively and quantitatively different. These alterations were greater in
      animals in the AlF3 group than in the NaF group and greater in the NaF group than
      in controls.

PMID- 9518652
TI  - Specific group II metabotropic glutamate receptor activation inhibits the
      development of kindled epilepsy in rats.
AB  - The effects of intracerebral administration of the group II metabotropic
      glutamate receptor agonist, 2R,4R-APDC, were tested on both the development of
      amygdaloid kindling and on fully developed stage 5 amygdala kindled seizures. The
      development of amygdaloid kindling was significantly retarded in 2R,4R-APDC (10
      nmol in 0.5 microl) treated animals compared to control animals over a period of
      8 days. At a low dose, 2R,4R-APDC (0.1 nmol) caused a 42.5+/-26.6% increase of
      the generalised seizure threshold in fully kindled animals. As higher doses were
      administered, however, the changes in generalised seizure threshold were less
      marked, and even a small decrease in the threshold was seen (-19.6+/-5.36% at 10
      nmol). The agonist 2R,4R-APDC inhibited depolarization-induced release of [3H]d
      aspartate from cortical synaptosomes with an IC50 value of 0. 29 microM. This
      effect was maximal at 1 microM, and decreased with dose thereafter. These
      findings suggest that the selective activation of the group II metabotropic
      glutamate receptors by agonists such as 2R,4R-APDC may be of therapeutic
      potential in the treatment of seizure disorders.

PMID- 9518653
TI  - Relationship between polypeptide transcytosis and lymphoid tissue in the rabbit
      nasal mucosa.
AB  - It has been suggested that the specific transcytosis of polypeptides,
      demonstrated in rabbit nasal mucosa (upper concha), is involved in antigen
      sampling at the airway entry. To test this hypothesis, unidirectional
      transepithelial fluxes of carbocalcitonin (CCT Mw = 3362) from the mucosal to the
      submucosal side, and vice versa, were measured by radioimmunoassay every 30 min
      for 120 min and, from the difference, net absorption was determined in the upper
      concha and septum mucosae. The exposed mucosae were examined by quantitative
      histology; isolated scattered lymphoid cells/mm2 and volumes of lymphoid
      infiltrates and aggregates were quantified. CCT absorption was observed in the
      mucosae of the upper concha and septum provided that aggregates were present,
      being proportional to aggregate volume. No relationship was noted with isolated
      scattered lymphoid cells and infiltrates. Passive permeability was unaffected by
      lymphoid tissue. On this basis, the antigen sampling hypothesis seems to be at
      least partially substantiated.

PMID- 9518654
TI  - Impaired expression of long-term potentiation in hippocampal slices 4 and 48 h
      following mild fluid-percussion brain injury in vivo.
AB  - The effect of fluid percussion brain injury on hippocampal long-term potentiation
      (LTP) was investigated in hippocampal slices in vitro. Mild to moderate (1.7-2.1
      atm) lateral fluid percussion head injury or sham operation was produced in rats
      4 or 48 h prior to harvesting brain slices from the ipsilateral hippocampus.
      Field excitatory post-synaptic potentials (fEPSPs) were recorded in stratum
      radiatum of hippocampal subfield CA1 in response to electrical stimulation of the
      Schaffer collaterals. The initial slope of fEPSPs was used to investigate changes
      in synaptic strength prior to and following 100 or 200 Hz (1 s) tetanic
      stimulation. TBI significantly inhibited expression of LTP in hippocampal slices
      in vitro. Post-tetanus fEPSP slopes increased more than 100% in hippocampal
      slices from sham-operated animals but less than 50% in slices from rats following
      TBI. The data suggest that changes in functional synaptic plasticity in the
      hippocampus may contribute to cognitive disorders associated with TBI (traumatic
      brain injury). The data also indicate that TBI-induced effects on hippocampal LTP
      are robust and may be investigated in the hippocampal slice preparation in vitro.

PMID- 9518655
TI  - In cortical cultures of trisomy 16 mouse brain the upregulated metallothionein
      I/II fails to respond to H2O2 exposure or glutamate receptor stimulation.
AB  - To assess whether a defective oxidative defense may contribute to Down's
      syndrome, we studied the regulation of the metallothionein(MT)-I/II isoforms in
      primary cultures of cerebral cortex from fetal trisomy 16 mice and their euploid
      littermates. Western blot analysis showed that MT-I/II was upregulated and the
      protein carbonyl content was higher in trisomy 16 compared with euploid cultures.
      Addition of N-acetyl-l-cysteine to the culture medium reduced the increment of MT
      I/II in trisomy 16 cortical cells. In euploid, but not trisomic cortical
      cultures, kainic acid, trans-(+/-)-ACPD, or H2O2 exposure elicited a dose
      dependent increase of the MT-I/II immunoblots. In trisomic cells, the MT-I/II
      immunoblot densities were not increased beyond their elevated basal levels. In
      contrast, 25 microM Pb induced MT-I/II, to a similar extent, in cortical cultures
      from euploid and trisomy 16 mice. This suggests that the antioxidant-but not the
      metal-response element of the MT-I/II promoter was altered by increased oxidative
      stress. Our data suggest that, in the trisomy 16 mouse, the effects of increased
      production of reactive oxygen species, due to the increased SOD-1, GluR5, or
      amyloid precursor protein gene dosage, is exacerbated by an insufficient or
      missing antioxidant response.

PMID- 9518656
TI  - Comparison of the myogenic response in rat cerebral arteries of different
      calibers.
AB  - The myogenic response, the characteristic of blood vessels to contract with
      increasing pressure, was studied at three different locations along the middle
      cerebral artery (MCA) vascular tree. We hypothesized that smaller caliber vessels
      would have a more pronounced myogenic response at lower pressures than larger
      diameter arteries, corresponding to pressures normally experienced in vivo.
      Cerebral vessels (MCAs, branches of the MCA, and penetrating arterioles) were
      isolated from male rats, cannulated with glass micropipettes, and pressurized.
      Changes in diameter were measured as the transmural pressure was increased from
      20-100 mmHg. The MCAs, which had a resting diameter of 202 +/- 10 micron (n = 9)
      at 50 mmHg, showed its greatest myogenic response between 60-100 mmHg (8+/-2%
      constriction, n = 9, p < 0.001). The penetrating arterioles [58 +/- 4 micron (n =
      8) at 50 mmHg], on the other hand, showed its greatest myogenic response between
      20-60 mmHg (10 +/- 4% constriction, n = 8, p < 0.05). Branches of the MCA [118 +/
      14 micron (n = 8) at 50 mmHg] showed a slight constriction over the entire
      pressure range (5 +/- 9% constriction between 20-100 mmHg, p=ns). Our results
      suggest that the myogenic response appears to be best developed in the range of
      pressures found during physiological conditions for a given vessel in the MCA
      territory. This characteristic is fundamental in the overall control of
      cerebrovascular resistance.

PMID- 9518657
TI  - The effect of ATP-depletion on the inhibition of glucose exits from human red
      cells.
AB  - The effect of ATP-depletion or its consequence, by metabolic inhibition, on the
      inhibition of glucose transport by various inhibitors was studied in human red
      cells. In cells depleted of ATP, glucose exit times were longer than in normal
      cells and the times increased with the duration of depletion. The Km for external
      glucose was higher in ATP-depleted cells than in normal undepleted cells (3.0 mM
      c.f. 2.5 mM at 30 degrees C). In contrast, the apparent Ki for cytochalasin B
      decreased from 0.85 microM in the normal cells to 0.5 microM after ATP-depletion.
      Half-maximal rates of glucose exit in the absence, and in the presence of 2
      microM cytochalasin B were found at ATP concentrations of 0.43 and 0.68 microM,
      respectively. Although glucose exits from ATP-depleted cells exposed to the
      irreversible inhibitor of glucose transport, 1-fluoro-2,4-dinitrobenzene (FDNB)
      were slower than in normal cells, the relative degrees of inhibition were not
      significantly different. However, normal and ATP-depleted cells responded
      differently to treatment with 1,2-cyclohexanedione, a modifier of arginine
      residues which inhibits glucose exit. While normal cells were markedly inhibited,
      depleted cells were much less affected and the inhibitory effect of cytochalasin
      B seen in normal cells was reduced. These findings demonstrate that the glucose
      transport system of human red cells is affected by intracellular ATP and that ATP
      alters the affinity of the transporter for certain inhibitors. The implications
      of these findings are discussed.

PMID- 9518658
TI  - Increased calpain expression in experimental demyelinating optic neuritis: an
      immunocytochemical study.
AB  - Since calcium activated neutral proteinase (calpain) is present in the central
      nervous system (CNS) and degrades myelin proteins, this endopeptidase has been
      suggested to play a role in myelin destruction in demyelinating diseases such as
      multiple sclerosis (MS). In the present study, calpain immunocytochemical
      expression was examined in Lewis rats with acute experimental allergic
      encephalomyelitis (EAE), an animal model for MS and optic neuritis. To identify
      cells expressing calpain, we labeled rat optic nerve sections for calpain with a
      polyclonal myelin calpain antibody and with monoclonal antibodies for glial
      (GFAP, OX42) and inflammatory (CD2, ED2, ED1, IFN-gamma) cell-specific markers.
      The results showed increased calpain expression in microglia (OX42) and
      infiltrating macrophages (ED1,2) in EAE compared to normal controls. Astrocytes
      constitutively expressed calpain in controls and acute EAE. Reactive astrocytes
      in EAE located in or near inflammatory foci, exhibited markedly increased calpain
      expression. Most T cells in acute EAE showed low level calpain expression while
      activated IFN-gamma-producing lymphocytes in inflammatory foci exhibited elevated
      levels of calpain expression. Thus, our results demonstrate increased calpain
      expression (at transcriptional and/or translational levels) in a rat model of
      optic neuritis. A role for calpain in myelin destruction during optic neuritis
      may be relevant to the pathogenesis of this disorder.

PMID- 9518659
TI  - Tolerance to catalepsy following chronic haloperidol is not associated with
      changes in GABA release in the globus pallidus.
AB  - In vivo microdialysis was used to investigate the relationship between
      extracellular GABA levels in rat globus pallidus following acute (1st injection)
      and chronic (29th injection) haloperidol (Hal) (0.25 mg kg-1 day-1, s.c.) with
      the presence and absence of catalepsy, respectively. There was no difference in
      basal pallidal GABA levels in the drug naive and chronically treated rats.
      Furthermore, pallidal GABA release was not affected following injection with Hal
      in either group although there was a prolonged catalepsy in the drug naive group
      and a tolerance to catalepsy in the chronically treated group. A previous
      microdialysis study employing similar experiment protocol showed that Hal
      increases striatal GABA release in drug naive rats and increases basal striatal
      GABA levels following chronic treatment. The results of the current study
      demonstrate that these effects are not reflected in the globus pallidus and
      suggest that striatal GABA interneurons and/or GABA projection neurons to
      extrapallidal nuclei such as the substantia nigra pars reticulata may be involved
      in initiating catalepsy following acute Hal and mediating the tolerance to
      catalepsy observed following chronic Hal.

PMID- 9518661
TI  - Thalamic paraventricular nucleus neurons collateralize to innervate the
      prefrontal cortex and nucleus accumbens.
AB  - The prefrontal cortex and nucleus accumbens are primary recipients of medial
      thalamic inputs, prominently including projections from the thalamic
      paraventricular nucleus. It is not known if paraventricular neurons collateralize
      to innervate both the prefrontal cortex and nucleus accumbens. We used dual
      retrograde tract tracing methods to examine this question. A small population of
      paraventricular neurons was found to innervate the prefrontal cortex and medial
      nucleus accumbens. These data suggest that the thalamic paraventricular nucleus
      may coordinately influence activity in the prefrontal cortex and ventral
      striatum.

PMID- 9518660
TI  - Activation of mitogen-activated protein kinases is not required for the extension
      of neurites from PC12D cells triggered by nerve growth factor.
AB  - Numerous studies with PC12 cells have suggested that the mitogen-activated
      protein (MAP) kinase pathway might play a major role in the neuronal
      differentiation that is induced by nerve growth factor (NGF). Cells of the PC12D
      subline extend neurites within several hours in response to NGF in the presence
      of inhibitors of the synthesis of RNA and protein. We examined the effects of a
      specific inhibitor 2-(2'-amino-3'-methoxyphenyl)-oxanaphthalen-4-one (PD98059) of
      the MAP kinase kinase (MEK)/MAP kinase pathway on the NGF-induced outgrowth of
      neurites in PC12D cells. The increase in MAP kinase activity in response to NGF
      was reduced by 80% upon treatment of PC12D cells with 50 microM PD98059, whereas
      the NGF-dependent formation of ruffles and the subsequent outgrowth of neurites
      were not blocked by PD98059 at this concentration. The outgrowth of neurites from
      conventional PC12 cells by NGF was suppressed by the addition of 50 microM
      PD98059 as reported by Pang et al. [L. Pang, T. Sawada, J. Stuart,S.J. Decker,
      A.R. Saltiel, Inhibition of MAP kinase kinase blocks the differentiation of PC12
      cells induced by nerve growth factor, J. Biol. Chem. 270 (1995) 13585-13588]. In
      contrast, the rapid regeneration of neurites from PC12 cells primed with NGF, was
      not altered in the presence of the same dose of the inhibitor of MEK. It
      appeared, therefore, that the activation of the MAP kinase pathway was not
      necessarily required for the NGF-dependent extension of neurites. When PC12D
      cells were transfected with the dominant inhibitory Ha-ras Asn-17 gene, the
      induction of the mutant Ras protein led the suppression of the rapid outgrowth of
      neurites in response to NGF but not to dibutyryl cyclic AMP (dbcAMP). The result
      implies a direct involvement of Ras protein in the NGF-induced signal
      transduction that lead to the formation of neurites in PC12D cells. We can
      conclude that the activation of MAP kinase and selective gene expression are
      required for the differentiation of conventional PC12 cells to sympathetic neuron
      like cells and that activation of Ras protein and, subsequently, of a MAP kinase
      independent pathway might be involved in the extension of neurites from PC12D
      cells or in the regeneration of neurites from primed PC12 cells in response to
      NGF.

PMID- 9518662
TI  - Solubilization of planar bilayers with detergent.
AB  - The interaction of the nonionic detergent Triton X-100 with supported
      phosphatidylcholine planar lipid bilayers has been investigated by optically
      monitoring changes in the bilayer, using the technique of optical waveguide
      lightmode spectroscopy (OWLS). This technique has several advantages over the
      methods applied to the problem hitherto, including: high sensitivity; measurement
      in situ with good time resolution; the fact that the free detergent concentration
      is well-defined, and the lipid concentration in solution is zero; ease of
      studying the reversibility of the interaction; and the readiness with which
      absolute rather than effective amounts of detergent incorporated into the lipid
      can be determined. The main finding is that as the free Triton concentration
      increases, the detergent is first incorporated reversibly into the bilayer, then
      partly but never completely removes lipid, and finally (at or above the cmc)
      completely solubilizes the bilayer. The behaviour of the lanar supported lipid
      bilayers is thus similar to that previously reported for lipid vesicles.

PMID- 9518663
TI  - Effect of injection of antisense oligodeoxynucleotides of GAD isozymes into rat
      ventromedial hypothalamus on food intake and locomotor activity.
AB  - In the ventromedial hypothalamus (VMH), gamma-aminobutyric acid (GABA) plays a
      role in regulating feeding and running behaviors. The GABA synthetic enzyme,
      glutamic acid decarboxylase (GAD), consists of two isozymes, GAD65 and GAD67. In
      the present study, the phosphorothioated antisense oligodeoxynucleotides (ODNs)
      of each GAD isozyme were injected bilaterally into the VMH of male rats, and food
      intake, body weight and locomotor activity were monitored. ODNs were incorporated
      in the water-absorbent polymer (WAP, 0.2 nmol/microliter) so that ODNs were
      retained at the injection site. Each antisense ODN of GAD65 or GAD67 tended to
      reduce food intake on day 1 (day of injection=day 0) though not significantly. An
      injection combining both antisense ODNs significantly decreased food intake only
      on day 1, but body weight remained significantly lower than the control for 5
      days. This suppression of body weight gain could be attributed to a significant
      increase in locomotor activity between days 3 and 5. Individual treatment with
      either ODNs did not change locomotor activity. The increase in daily locomotor
      activity in the group receiving the combined antisense ODNs occurred mainly
      during the light phase. Neither vehicle (WAP) nor control ODN affected food
      intake, body weight and locomotor activity. Histological studies indicated that
      antisense ODN distributed within 800 micron from the edge of the area where WAP
      was located 24 h after the injection gradually disappeared within days, but still
      remained within 300 micron m distance even 7 days after the injection. Antisense
      ODN was effectively incorporated by all the cell types examined, i.e., neurons,
      astrocytes and microglias. Further, HPLC analysis revealed that antisense ODNs of
      GAD isozymes, either alone or combined, decreased the content of GABA by 50% in
      VMH 24 h after the injection. These results indicate that suppression of GABA
      synthesis by either of the GAD isozymes is synergistically involved in
      suppressing food intake and enhancing locomotor activity in rat VMH.

PMID- 9518664
TI  - Muscimol suppression of the dorsal cochlear nucleus modifies frequency tuning in
      rats.
AB  - The cochlear nucleus is composed of three sub-nuclei: the dorsal (DCN),
      anteroventral (AVCN) and posteroventral cochlear nucleus (PVCN). Intrinsic
      connections from the DCN to the AVCN are inhibitory and organised tonotopically.
      In this investigation, this pathway and its possible role in frequency tuning was
      examined using in vivo extracellular recordings. Extracellular recordings were
      made from 191 units in the AVCN, 69 of which were recorded after suppression of
      DCN by application of the GABA agonist Muscimol (15 ng, 0.26 mM). Tuning curves
      were plotted and characteristic frequency (CF) and response threshold (measured
      in dB SPL) were determined for each unit. Units recorded post-Muscimol showed
      significantly broader tuning characteristics and lower thresholds. Primary-like
      and transient chopper neurons contributed to this decrease in threshold
      suggesting that they receive 'on' CF inhibitory drive from the DCN. Sustained
      chopper units did not show a significant decrease in response threshold after
      Muscimol; however, there was a tendency for broader tuning and a significant
      increase in CF tone evoked maximum discharge rate and chopping frequency
      suggesting that the DCN may play a role in regulating the temporal firing of
      these units in addition to providing lateral inhibition. These results suggest
      that the DCN to AVCN pathway may aid in fine tuning frequency information.

PMID- 9518665
TI  - Alamethicin-like behaviour of new 18-residue peptaibols, trichorzins PA. Role of
      the C-terminal amino-alcohol in the ion channel forming activity.
AB  - The influences of peptide length, absence of a Glx (Gln/Glu) residue and the C
      terminal amino alcohol on liposome permeabilization and ion-channel
      characteristics in planar lipid bilayers were examined with two 18-residue
      peptaibols, PA V and PA IX. As compared to the 20-residue alamethicin, both
      peptides belonging to the newly isolated trichorzin family, lack a proline in the
      N-terminal part and one of the two Gln/Glu residues in the C-terminal part of the
      sequence. The two analogues studied here differ among themselves in their C
      terminal amino alcohol (tryptophanol for PA V and phenylalaninol for PA IX).
      These alpha-helical peptaibols modify to a similar extent the permeability of
      liposomes, as measured by leakage of a previously entrapped fluorescent probe.
      Monitoring tryptophanol fluorescence, a greater embedment of the peptide PA V is
      observed in cholesterol-free bilayers. Macroscopic conductance studies for PA V
      and PA IX display alamethicin-like current-voltage curves, with a similar voltage
      dependence, but a smaller mean number of monomers per conducting aggregate is
      estimated for the tryptophanol analogue, PA V. Single-channel recordings indicate
      faster current fluctuations for PA IX, while amplitude histograms show lower
      conductance levels for PA V. Apart from underlining the role of the mismatch
      between helix length and bilayer hydrophobic thickness, these results stress that
      the C-terminal tryptophanol favours a stabilization of the conducting aggregates.

PMID- 9518666
TI  - Evidence for reduced nitric oxide synthase (NOS) activity in the ipsilateral
      medial vestibular nucleus and bilateral prepositus hypoglossi following
      unilateral vestibular deafferentation in the guinea pig.
AB  - The aim of the present study was to examine, using a radioenzymatic assay
      technique, nitric oxide synthase (NOS) activity in the bilateral medial
      vestibular nuclei (MVN) and prepositus hypoglossi (PH), during the development of
      vestibular compensation for unilateral vestibular deafferentation (UVD) in the
      guinea pig. In the MVN ipsilateral to the UVD, and bilaterally in PH, NOS
      activity decreased following UVD compared to sham controls and did not recover
      significantly up to 50 h later, when a substantial degree of behavioural
      vestibular compensation had occurred. These results suggest that UVD causes a
      decrease in NOS activity in the ipsilateral MVN and the bilateral PH, and that a
      consequent decrease in NO may be responsible for some of the ocular motor and
      postural symptoms of UVD.

PMID- 9518667
TI  - Arachidonic acid inhibits both K+ and Ca2+ currents in isolated type I cells of
      the rat carotid body.
AB  - Whole-cell patch-clamp recordings were used to investigate the effects of
      arachidonic acid (AA) on K+ and Ca2+ channels in isolated rat type I carotid body
      cells. AA (2-20 microM) produced a concentration-dependent inhibition of both K+
      currents and Ca2+ channel currents. The effects of AA on K+ currents were
      unaffected by indomethacin (5 microM), phenidone (5 microM) or 1
      aminobenzotriazole (3 mM), suggesting that AA did not exert its effects via cyclo
      oxygenase, lipoxygenase or cytochrome P-450 (cP-450) metabolism. Our results
      suggest that AA directly and non-selectively inhibits ionic currents in rat type
      I carotid body cells.

PMID- 9518668
TI  - Effect of preceding in vivo sublethal ischemia on the evoked potentials during
      secondary in vitro hypoxia evaluated with gerbil hippocampal slices.
AB  - We investigated the mechanism of 'ischemic tolerance phenomenon' by
      characterizing the physiological events, modified by preceding sublethal
      ischemia, during secondary hypoxia. Slices from brains after pretreatment of
      sublethal forebrain ischemia were subjected to a 70% reduction of PO2 (threshold
      hypoxia). Although evoked potentials disappeared completely in five of eight
      slices from sham-operated brain, they were sustained in 28/32 slices from
      pretreated brains. This study indicates that the maintenance of membrane function
      might be the mechanism of ischemic tolerance.

PMID- 9518669
TI  - Brain ANG II and prostaglandins mediate the pressor response after central
      blockade of nitric oxide synthase.
AB  - Central inhibition of nitric oxide synthase (NOS) by intracerebroventricular
      (i.c.v.) administration of NG-nitro-l-arginine methyl ester (L-NAME; 150 microg/5
      microl) to conscious rats produced a biphasic pressor response characterized by
      an initial transient increase within 5 min, and a delayed response starting
      between 60-90 min. The effect was stereospecific, as D-NAME (250 microg/5 microl)
      did not modify the resting arterial blood pressure, nor did L-arginine (323
      microg/5 microl, i.c.v.), indicating the substrate for NOS is not rate-limiting.
      Intracerebroventricular pretreatment with losartan (25 microg/5 microl), a non
      peptide antagonist of the angiotensin II AT1 receptor subtype, or indomethacin
      (100 microg/5 microl), a blocker of cyclooxygenase, however, prevented the
      initial increase in blood pressure without affecting the delayed pressor
      response. In contrast, neither intravenous losartan (10 mg/kg b.wt) nor prazosin,
      an alpha1 adrenergic receptor antagonist, at doses of 5 microg/5 microl (i.c.v.)
      or 0.3 mg/kg b.wt (i.v.) were effective in altering the pressor responses. These
      results indicate that centrally produced NO maintains the resting arterial blood
      pressure at least partially through modulation of the brain angiotensin system
      and prostaglandins.

PMID- 9518670
TI  - Phosphate-enhanced transfection of cationic lipid-complexed mRNA and plasmid DNA.
AB  - Cationic lipid-mediated gene transfer has been shown to be a competent albeit
      inefficient mechanism of promoting cellular gene transfer. One way to improve the
      efficacy of cationic lipid-mediated transgene expression is to optimize
      conditions for complex formation between the lipids and nucleic acids. In this
      report we describe the beneficial effects of using phosphate buffer to
      precondition lipofectin (a 1:1 (w/w) mixture of N-[1-(2,3-dioleyloxy)propyl]-n,n,
      n-trimethylammonium chloride (DOTMA), and dioleoyl phosphatidylethanolamine
      (DOPE)) prior to complexing with plasmid DNA or mRNA. Under such optimized
      conditions we studied the kinetics of DNA- and RNA-mediated transgene expression
      in a human osteosarcoma cell line (HOS). Preincubation of lipofectin in phosphate
      buffer resulted in up to 26- and 56-fold increases in luciferase expression from
      plasmid DNA and mRNA, respectively. Addition of chloroquine (50 microM), which
      enhanced plasmid-mediated gene delivery 3-fold, was synergistic with phosphate
      resulting in an additional 46-fold increase in luciferase expression. The
      preincubation with phosphate shortened both the time required for cellular uptake
      and the time to achieve maximal transgene expression. Optimal transfection was
      achieved in the presence of 30-80 mM phosphate, at pH 5.6-6.8 under which the
      phosphate anion is divalent. The effect of phosphate anion was specific in that
      monovalent Cl- and acetate anions were not stimulatory. These results demonstrate
      that divalent phosphate anion plays a stimulatory role during complex formation
      and transfection when cationic lipids come in contact with negatively charged
      nucleic acids and cell membranes. These findings delineate specific conditions
      which dramatically enhance transfection efficiency for both DNA and mRNA, and
      provide an effective procedure for gene transfection studies.

PMID- 9518671
TI  - Effects of gender and estradiol treatment on focal brain ischemia.
AB  - The present studies were undertaken to investigate the effects of gender and
      estrogen treatment on focal cerebral ischemia in male and female rats. Focal
      ischemia was created by inserting a 3-0 surgical suture through the left cervical
      internal carotid artery to obstruct the blood flow into the middle cerebral
      artery (MCA). The MCA was reperfused by removing the suture in 40 min. All rats
      were sacrificed for measurement of infarct area after 24 h. In the first study,
      mortalities from MAC occlusion were 12.5% (2/16) each for intact male rats and
      intact female rats, and 23.5% (4/17) for ovariectomized (OVX) female rats. The
      coronal infarct area (mean+/-S. E.M.) was 9.5+/-1.0% for intact female rats,
      16.6+/-1.6% for intact male rats (p=0.0001 vs. intact female rats), and 16.0+/
      1.4% for OVX female rats (p=0.0002 vs. intact female rats). In a second
      experiment, OVX-female rats were administrated either 17beta-estradiol (E2) or
      its vehicle, hydroxypropyl-beta-cyclodextrin (HPCD), at 40 min after the onset of
      MCA occlusion. Mortalities were 40% (4/10) for vehicle treated OVX rats and 0%
      for E2 treated OVX rats. The coronal infarct area (mean+/-S.E.M.) was 19.3+/-1.8%
      for vehicle treated rats vs. 8.0+/-1. 2% for E2 treated rats (p<0.01). Serum
      estrogen levels for vehicle treated OVX rats were 14.5+/-1.2% pg/ml vs. 142.7+/
      23.6 pg/ml for E2 treated OVX rats (p<0.01). These results strongly suggest that
      the level of circulating estrogens play an important role in protecting brain
      tissues against ischemia induced by MCA occlusion.

PMID- 9518672
TI  - Effect of adrenalectomy on cocaine facilitation of medial prefrontal cortex self
      stimulation.
AB  - Adrenalectomy (ADX) is known to block the acquisition of intravenous cocaine self
      administration. A previous study therefore examined whether ADX decreases
      sensitivity of the 'brain reward system' in general, or its response to cocaine
      in particular, by measuring thresholds for intracranial self-stimulation with and
      without concurrent cocaine administration. ADX had no effect on thresholds for
      lateral hypothalamic self-stimulation (LHSS) and did not alter the cocaine dose
      response curve for lowering the LHSS threshold. This result suggested that ADX
      does not affect sensitivity of the brain reward system. However, medial
      prefrontal cortex (MPFC) appears to be an important site in the mediation of
      cocaine reinforcing effects, and MPFC self-stimulation (MPFCSS) is mediated by a
      neural substrate that is largely independent of that which mediates LHSS. The
      present study therefore assessed whether ADX diminishes cocaine facilitation of
      MPFCSS. It was found that the threshold-lowering effect of cocaine (5.0, 10.0 and
      20.0 mg/kg, i.p. ) did not differ between ADX rats maintained on 0.7% saline, ADX
      rats maintained on corticosterone (50 microg/ml) in 0.7% saline, and sham
      operated controls. However, there was a trend toward desensitization of MPFCSS,
      itself, following ADX in the group that did not receive corticosterone
      supplementation. Based on this observation, and the similar responses of MPFCSS
      and cocaine self-administration to noncontingent priming stimulation, stress, and
      NMDA receptor antagonism, it is speculated that acquisition of MPFCSS and cocaine
      self-administration may be dependent upon a common sensitization process that is
      regulated by corticosterone.

PMID- 9518673
TI  - Reduced MK801 binding in neocortical neurons after AAV-mediated transfections
      with NMDA-R1 antisense cDNA.
AB  - Two adeno-associated virus (AAV)-derived plasmids were constructed with portions
      of the N-methyl-d-aspartic acid-R1 (NMDA-R1) receptor subunit downstream from the
      AAV p40-(pJDT95dlk-aR1) or cytomegalovirus (CMV) promoter (pTRUF3-aR1) in an
      antisense orientation. Each plasmid drove expression of antisense NMDA-R1 in
      primary rat neocortical neuronal cultures 4 days after transfection as detected
      by reverse transcriptase-polymerase chain reaction (RT-PCR). Transfection with
      pTRUF3-aR1 (2x4 microgram) but not with pJDT95dlk-aR1 decreased neuronal [3H]MK
      801 binding in a dose-dependent manner.

PMID- 9518674
TI  - Norepinephrine transmitter metabolite generates free radicals and activates
      mitochondrial permeability transition: a mechanism for DOPEGAL-induced apoptosis.
AB  - 3,4-Dihydroxyphenylglycolaldehyde (DOPEGAL) is the monoamine oxidase A metabolite
      of norepinephrine (NE) and epinephrine. DOPEGAL, but neither NE nor its other
      metabolites induces apoptosis in differentiated PC-12 cells by an unknown
      mechanism. To study the mechanism of DOPEGAL-induced apoptosis, we tested DOPEGAL
      and NE for their capacity to generate free radicals and to induce mitochondrial
      permeability transition (PT). Results show that DOPEGAL but not NE forms reactive
      free radical intermediates under oxidative stress and enhances Ca2+-mediated
      induction of the mitochondrial PT. Linkage of these events to apoptosis is
      described. Implications for degenerative diseases are discussed.

PMID- 9518675
TI  - Local connections between the columns of the periaqueductal gray matter: a case
      for intrinsic neuromodulation.
AB  - Chemical stimulation of the lateral or ventrolateral columns of the midbrain
      periaqueductal gray matter (PAG) in conscious animals produces opposite responses
      (viz., defensive behavior and pressor responses from the lateral column vs.
      quiescence and depressor responses from the ventrolateral column), raising the
      possibility that the two columns are interconnected. To test this hypothesis, two
      types of anatomical experiments were performed in rats. First, the anterograde
      axonal marker Phaseolus vulgaris leuco-agglutinin (PHA-L) was injected into
      individual PAG columns or adjoining regions which included the Edinger-Westphal,
      dorsal raphe, and precommissural nuclei. The results shows that each column
      projects bilaterally to all of the other PAG columns, and also provides local
      connections within its own column. Furthermore, the Edinger-Westphal and
      precommissural nuclei project to all four PAG columns, while the dorsal raphe
      nucleus projects only to the ventrolateral and lateral columns. In a second
      experiment, we found that cardiovascular-related PAG projection neurons of both
      the lateral and ventrolateral columns receive an input from the reciprocal PAG
      column. This was demonstrated by a double tracer neuroanatomical study in which
      PHA-L was first iontophoretically ejected into either the lateral or
      ventrolateral PAG columns and then, several days later the retrograde
      transneuronal viral tracer, pseudorabies virus, was injected into the stellate
      sympathetic ganglion. Intra-PAG circuits were visualized by a dual
      immunohistochemical procedure. These results suggest that during the fight-or
      flight response when the 'fight' program is activated, inhibition of the 'flight'
      PAG network may occur and the converse situation may occur during the flight
      response.

PMID- 9518676
TI  - Substance P immunoreactive nerve terminals in the dorsolateral nucleus of the
      tractus solitarius: roles in the baroreceptor reflex.
AB  - Physiological and light microscopic evidence suggest that substance P (SP) may be
      a neurotransmitter contained in first-order sensory baroreceptor afferents;
      however, ultrastructural support for this hypothesis is lacking. We have traced
      the central projections of the carotid sinus nerve (CSN) in the cat by utilizing
      the transganglionic transport of horseradish peroxidase (HRP). The dorsolateral
      subnucleus of the nucleus tractus solitarius (dlNTS) was processed for the
      histochemical visualization of transganglionically labeled CSN afferents and for
      the immunocytochemical visualization of SP by dual labeling light and electron
      microscopic methods. Either HRP or SP was readily identified in single-labeled
      unmyelinated axons, myelinated axons, and nerve terminals in the dlNTS. SP
      immunoreactivity was also identified in unmyelinated axons, myelinated axons, and
      nerve terminals in the dlNTS, which were simultaneously identified as CSN primary
      afferents. However, only 15% of CSN terminals in the dlNTS were immunoreactive
      for SP. Therefore, while the ultrastructural data support the hypothesis that SP
      immunoreactive first-order neurons are involved in the origination of the
      baroreceptor reflex, they suggest that only a modest part of the total sensory
      input conveyed from the carotid sinus baroreceptors to the dlNTS is mediated by
      SP immunoreactive CSN terminals. Five types of axo-axonic synapses were observed
      in the dlNTS. SP immunoreactive CSN afferents were very rarely involved in these
      synapses. Furthermore, SP terminals were never observed to form the presynaptic
      element in an axo-axonic synapse with a CSN afferent. Therefore, SP does not
      appear to be involved in the modulation of the baroreceptor reflex in the dlNTS.

PMID- 9518678
TI  - Bacterial endotoxin alters kinetics of BK channels in rat cerebrovascular smooth
      muscle cells.
AB  - Patch-clamp recordings were used to study the effects of Escherichia coli
      bacterial endotoxin (lipopolysaccharide, LPS) on the properties of large
      conductance, Ca2+-dependent K+ channels (BK channels) in the membrane of
      enzymatically dispersed rat cerebrovascular smooth muscle cells (CVSMCs). LPS had
      negligible effects on the kinetic and conductance properties of BK channels when
      applied to the extracellular domain of these channels. However, acute application
      of LPS (10-100 microg/ml) to inside-out patches of CVSMC membrane isolated in a
      cell-free environment rapidly and reversibly increased the open probability of BK
      channels, leaving the conductance of these channels unaltered. The magnitude of
      this effect decreased as the concentration of free Ca2+ at the cytoplasmic
      membrane face was lowered, but was little affected by changes in membrane
      potential. Kinetic analysis showed that LPS accelerated reopening of BK channels
      while having little effect on mean channel open time. Detoxified E. coli LPS,
      from which the fatty acid chains of Lipid A were partially removed, showed
      slightly reduced activity when compared to the parent endotoxin molecule. A
      purified E. coli Lipid A had negligible effects on BK channel function. These
      results indicate that LPS activates BK channels in cerebrovascular smooth muscle
      cells when present at the cytoplasmic membrane face. This novel mechanism may
      provide insights into the regulation of BK channels by intracellular, membrane
      associated elements.

PMID- 9518679
TI  - Perivascular localization of nitric oxide synthase in the rat adenohypophysis:
      potential implications for function and cell-cell interaction.
AB  - The possible localization of nitric oxide (NO) synthase (NOS) in proximity to the
      microvasculature was examined in the rat adenohypophysis using
      immunohistochemistry and nicotinamide adenine dinucleotide phosphate diaphorase
      histochemistry. A population of NOS-positive cells was localized in very close
      contact with the sinusoidal capillaries. The pattern of this perivascular
      localization was either unicellular, bicellular or multicellular. These
      observations suggest that, at least, some actions of NO in the adenohypophysis
      can be accounted for by a local regulation of the glandular microvasculature.

PMID- 9518677
TI  - Effect of chronic amitriptyline administration on serotonergic receptors in rats
      with methylazoxymethanol-induced microencephaly.
AB  - Methylazoxymethanol (MAM)-induced cortical hypoplasia resulted in a 20% decrease
      in the Bmax of 5-HT2A receptors in the frontal cortex with no change in the Bmax
      of 5-HT1A receptors. Chronic treatment with amitriptyline did not further
      decrease the Bmax of 5-HT2A receptors in the MAM-lesioned cortex, suggesting that
      the persistent down-regulation of cortical 5-HT2A receptors in MAM-lesioned rats
      was induced by serotonergic hyperinnervation.

PMID- 9518680
TI  - A newly synthesized neurotropic pyrimidine compound, MS-818, may activate
      migratory schwann cells in peripheral nerve regeneration.
AB  - Following transection of a peripheral nerve in mice, a newly synthesized
      neurotropic pyrimidine compound, MS-818 was administered intraperitoneally at a
      dose of 1 mg kg-1 b.wt. day-1. The film model experiments for analyzing the early
      growth of axonal regeneration suggested that MS-818 activated Schwann cells which
      migrate from the proximal stump, inducing axonal elongation in vivo.

PMID- 9518682
TI  - The cellular distribution of GAP-43 immunoreactivity in human neocortical areas
      using immunofluorescence and confocal microscopy: post-ischemic influence.
AB  - The distribution of growth associated protein-43 (GAP-43) immunoreactive (IR)
      neurons were studied in human neocortical areas, using immunofluorescence and
      confocal microscopy. The GAP-43-IR cells were generally localised close to blood
      vessels, and contained fewer lipofuscin granules than GAP-43 negative cells.
      Quantification of the relative number of GAP-43-IR cells in control cases showed
      that the highest number of GAP-43-IR cells were present in layers III and V in
      the motor and visual cortices, fewer in the temporal cortex, and the lowest
      number in the frontal cortex. After general ischemia, GAP-43-IR cells were
      significantly reduced at various survival times, with the counts being lowest in
      the 1 week surviving case, and higher, but still subcontrol, in the 1 year post
      ischemic case.

PMID- 9518681
TI  - Divergent corticostriatal projections from a single cortical column in the
      somatosensory cortex of rats.
AB  - We injected biotinylated dextran amine (BDA) into single vibrissal 'barrels' of
      primary somatosensory (SI) cortex and reconstructed the topography of labelled
      varicosities in the dorsolateral caudate-putamen. Plots of labelled varicosities
      revealed densely-packed clusters of corticostriatal arborizations along the
      dorsolateral edge of the caudate-putamen and sparsely-packed arborizations more
      medially. The medial and lateral clusters of labelled terminals were separated by
      regions of unlabelled neuropil and lead us to conclude that a single cortical
      column sends divergent projections to multiple regions of the caudate-putamen.

PMID- 9518683
TI  - Deprenyl decreases an endogenous parkinsonism-inducing compound, 1-benzyl-1,2,3,4
      tetrahydroisoquinoline in mice: in vivo and in vitro studies.
AB  - We examined the effect of deprenyl, a promising drug for the therapy of
      Parkinson's disease on the formation of a parkinsonism-inducing compound, 1
      benzyl-1,2,3,4-tetrahydroisoquinoline (1BnTIQ). The 1BnTIQ content was
      significantly decreased in the brain of deprenyl-treated mouse in vivo, and
      deprenyl also inhibited 1BnTIQ formation from phenethylamine by a mouse brain
      homogenate supernatant in vitro. In vivo, the content of a parkinsonism
      preventing compound, 1-methyl-1,2,3, 4-tetrahydroisoquinoline (1MeTIQ) was
      slightly increased in mice injected with deprenyl. The marked decrease of the
      ratio of 1BnTIQ to 1MeTIQ might play a role in the clinical effect of deprenyl.

PMID- 9518684
TI  - Muscarinic acetylcholine receptor subtypes in the human iris.
AB  - Employing subtype-specific antisera, we measured the relative immunoreactivity of
      five muscarinic acetylcholine receptor (mAChR) subtype proteins (m1-m5) in the
      human iris. The most intensive FITC immunofluorescence was detected by the anti
      m3 antibody, followed by anti-m1 and -m5 antisera, in the iris sphincter muscle
      cells. Only very weak fluorescence was obtained by anti-m2 and -m4 antibodies. In
      dilator muscle cells, weak but not consistent immunoreactivity was found by anti
      m1 and -m5 antibodies. The results suggest that the m3 muscarinic receptor is the
      predominant subtype in sphincter muscle cells of the human iris.

PMID- 9518685
TI  - Effect of melittin on PD, resistance and short-circuit current in the frog
      gastric mucosa.
AB  - In an in-vitro preparation of gastric mucosae of Rana pipiens, the effect of
      adding melittin to a concentration of 5x10-6 M in the secretory solution on the
      transepithelial potential difference (PD), resistance (R) and short-circuit
      current (Isc) was studied. In 20 min, melittin decreased the PD by 9.3 mV and R
      by 148 ohm cm2. These changes can be explained by a decrease in the resistance,
      RP, of the paracellular pathway. To determine whether specific-ion pathways were
      responsible for the decrease in R, the effect of melittin on the partial
      conductances of Cl-, K+ and Na+ was also studied using the ion substitution
      method. Melittin decreased the PD response to changes in nutrient Na+, K+ and Cl-
      and the PD response to changes in secretory Cl-, but did not affect PD responses
      to changes in secretory Na+ or K+. Therefore, melittin decreased the nutrient
      membrane partial conductances of Cl-, K+ and Na+ and secretory membrane partial
      conductance of Cl-, without affecting the secretory partial conductances of Na+
      or K+. Initially, melittin increased Isc in regular and Cl--free but not in Na+
      free solutions. There was a delayed decrease in Isc. The results indicate that
      melittin decreases RP, increases the Na+ conductance of the secretory membrane
      and inhibits, eventually, the Na+/K+-ATPase pump.

PMID- 9518686
TI  - Rapid increase in basal acetylcholine release in the hippocampus of freely moving
      rats induced by withdrawal from long-term ethanol intoxication.
AB  - The effect of ethanol withdrawal on hippocampal acetylcholine (ACh) release was
      investigated by brain microdialysis in rats rendered ethanol dependent by
      repeated forced administration of a 20% ethanol solution for 7 days. The
      behavioral signs of ethanol withdrawal were accompanied by an increase in
      hippocampal ACh output that was significantly 6 h after the last ethanol
      administration, reached a maximum (fourfold) at 12 h, and persisted for >72 h.
      Administration of diazepam (5 mg/kg, i.p.) or gamma-hydroxybutyrate (1 g/kg,
      intragastric) 12 h after the last ethanol administration completely antagonized,
      within 30 min, the increase in ACh output induced by ethanol withdrawal. Thus,
      the rapid and marked increase in ACh output might contribute to the changes in
      cognitive function associated with ethanol withdrawal, and the septohippocampal
      cholinergic system may play a major role in the response to withdrawal of
      addictive drugs.

PMID- 9518687
TI  - Quinpirole attenuates the striatal fos expression induced by escape behavior.
AB  - Several studies have shown that the D2-like dopamine receptor agonist quinpirole
      is able to markedly potentiate the striatal Fos expression induced by D1
      agonists. The present study examined the effects of quinpirole on the striatal
      Fos-like immunoreactivity (FLI) induced by escape behavior. Male rats were
      pretreated with either saline or quinpirole (0.156, 0.625, 1.25 or 2.5 mg/kg) and
      30 min later, placed in a shuttle box and required to crossover every 30 s in
      order to escape mild footshock. Animals were sacrificed 30 min following the
      completion of a 1-h block of escape trials and sections through the striatum were
      processed for FLI. Pretreatment with quinpirole produced a marked, dose
      dependent, attenuation of escape-induced FLI in the striatum. These findings
      demonstrate that quinpirole affects the striatal Fos expression induced by
      shuttling in a very different fashion than it does that induced by D1 agonists,
      and further support the view that dopaminergic mechanisms play an important role
      in behaviorally induced striatal Fos expression.

PMID- 9518688
TI  - Acute ammonia treatment in vitro and in vivo inhibits the synthesis of a
      neuroprotectant kynurenic acid in rat cerebral cortical slices.
AB  - The synthesis of kynurenic acid (KYNA) from kynurenine was measured in the
      cerebral cortical slices. In vitro, ammonium acetate at the subtoxic to toxic
      concentration range from 1 mM to 10 mM dose-dependently inhibited KYNA synthesis
      (IC50=2.99 mM). Ammonia treatment in vivo decreased KYNA synthesis by 30%. These
      results suggest that impaired neuroprotection exerted by KYNA might be a
      potential contributor to the glutamate receptor-mediated aspect of acute ammonia
      neurotoxicity.

PMID- 9518689
TI  - Widespread neuronal degeneration in rats following oral administration of
      methylmercury during the postnatal developing phase: a model of fetal-type
      minamata disease.
AB  - The neurotoxicity of methylmercury (MeHg) treatment during the postnatal
      developing phase in rats was studied. Rats on postnatal day 1 were orally
      administered 5 mg/kg/day methylmercury chloride (MMC) for more than 30
      consecutive days. Body weight loss began 26 days after MMC was administered, and
      severe paralysis of the hind-limbs and unsteadiness appeared subsequently.
      Histopathologically, the widespread neuronal degeneration was observed in the
      cerebral neocortex, neostriatum, red nucleus, brainstem, cerebellum and spinal
      dorsal root ganglia on day 32. The widespread distribution of the lesions was
      quite similar to that in fetal cases of MeHg intoxication in Minamata, Japan.
      These findings suggest that MMC treatment during the postnatal development phase
      in rats produce a good model of fetal-type Minamata disease.

PMID- 9518690
TI  - Dorsal root ganglion nerve cells transiently express increased immunoreactivity
      of the calcium-binding protein S-100beta after sciatic nerve transection.
AB  - Transiently increased immunoreactivity of the calcium binding protein S-100beta
      was demonstrated in spinal ganglion nerve cells after sciatic nerve transection.
      Neuropeptide Y (NPY), normally not seen in these nerve cells, appeared
      concomitantly. The transiently elevated co-expression of S-100beta and NPY is
      proposed to reflect an increased demand of neurotrophic and neuroprotective
      compounds in reactive neurons, tentatively regulating calcium ions.

PMID- 9518691
TI  - The development of nuchal atonia associated with active (REM) sleep in fetal
      sheep: presence of recurrent fractal organization.
AB  - The behavioral state of active or rapid eye movement sleep (REMS) is dominant
      during fetal life and may play an important role in brain development. One marker
      of this state in fetal sheep is neck nuchal muscle atonia (NA). We observed burst
      within burst NA patterns suggestive of recurrent fractal organization in
      continuous 13 day in utero recordings of NA during the third trimester.
      Consistent with fractal renewal processes, the cumulative mean and standard
      deviation (SD) diverged over this time and the tail of NA distributions fit a
      stable Levy law with exponents that remained invariant over the periods of
      development examined. The Hurst exponent, a measure of self-affine fractals,
      indicated that long-range correlations among NA intervals were present throughout
      development. A conserved complex fractal structure is apparent in NA which may
      help elucidate ambiguities in defining fetal states as well as some unique
      properties of fetal REMS.

PMID- 9518692
TI  - Novel role for the pontine micturition center, Barrington's nucleus: evidence for
      coordination of colonic and forebrain activity.
AB  - This report provides evidence for a novel role of Barrington's nucleus,
      considered the pontine micturition center, in regulation of colonic function.
      Barrington's activation elicited increases in colonic intraluminal pressure that
      were eliminated by scopolamine and intrathecal lidocaine, suggesting an impact of
      Barrington's neurons on colonic activity via projections to lumbosacral
      parasympathetic neurons. Consistent with this, Barrington's neurons were
      transsynaptically labeled from the distal colon by pseudorabies virus and several
      of these were also retrogradely labeled from the locus coeruleus, which projects
      extensively to the forebrain. Thus, Barrington's nucleus is strategically
      positioned to coordinate colonic and forebrain activity. Dysfunctions within this
      divergent system may underlie the frequent comorbidity of colonic and psychiatric
      symptoms.

PMID- 9518694
TI  - Selective dopamine neurotoxicity by an industrial chemical: an environmental
      cause of Parkinson's disease? 1.

PMID- 9518693
TI  - Effects of pentylenetetrazol kindling on glutamate receptor genes expression in
      the rat hippocampus.
AB  - It has been hypothesized that changes in the excitatory amino acid receptor
      biosynthesis may be involved in the mechanism of kindling-an animal model of
      epileptogenesis. In order to test this hypothesis, we investigated the effects of
      pentylenetetrazol kindling on the expression of genes coding for NMDAR1 and GluR2
      in the rat hippocampal formation. Pentylenetetrazol kindling decreased the
      hippocampal NMDAR1 mRNA level after 3 and 24 h; lowered the GluR2 flip level and
      elevated the flop mRNA one in the CA1 field and dentate gyrus after 3 and 24 h,
      respectively. A receptor autoradiography showed an increase in the [3H]MK-801
      binding density in the hippocampus following both acute and repeated
      pentylenetetrazol administration. We conclude that an early occurrence of
      downregulation of the glutamate receptor gene expression may be an adaptive
      response of glutamate receptors to an oversupply of excitatory amino acids during
      repeated seizures.

PMID- 9518695
TI  - Modulation of reconstituted ATP-sensitive K(+)-channels by GTP-binding proteins
      in a mammalian cell line.
AB  - 1. The action of GTP-binding proteins on ATP-sensitive potassium (KATP) channels
      was investigated. KATP channels were expressed in a mammalian cell line (COS-1
      cells) by cotransfecting vectors carrying the sulphonylurea receptor (SUR1) and
      BIR (Kir6.2), a member of the inward rectifier K+ channel family. G proteins were
      also tested on KATP channels composed of an isoform of SUR1, SUR2A, in
      combination with Kir6.2. 2. The alpha and beta gamma subunits of the GTP binding
      protein G1 were tested separately in inside-out patches under continuous
      recording. G alpha-11 increases the activity of SUR1-Kir6.2 and SUR2A-Kir6.2
      channels by 200 and by 30%, respectively. 3. G alpha-12 does not increase the
      activity of SUR1-Kir6.2 channels, but increase the activity of SUR2A-Kir6.2
      channels by 30%. 4. Control experiments showed that GTP gamma S, a specific
      activator of G proteins, and heat-inactivated G alpha-11 do not increase the
      single channel activity. 5. No effects of the other subunits (beta gamma) from
      either G11 or G12 on the single channel activity were observed. 6. The protein
      kinase C inhibitors H7 and an inhibitory peptide (FARKGALRQKNV) had no effect on
      the modulatory action of G alpha-11 on SUR1-Kir6.2 channels. 7. We conclude that
      both types of reconstituted KATP channels are modulated by G proteins.

PMID- 9518696
TI  - Role of receptor kinase in short-term desensitization of cardiac muscarinic K+
      channels expressed in Chinese hamster ovary cells.
AB  - 1. The cardiac muscarinic receptor-K+ channel system was reconstructed in Chinese
      hamster ovary (CHO) cells by transfecting the cells with the various components
      of the system. The activity of the muscarinic K+ channel was measured with the
      cell-attached configuration of the patch clamp technique. 2. In CHO cells
      transfected with the channel (Kir3.1/Kir3.4), receptor (hm2) and receptor kinase
      (GRK2), on exposure to agonist, there was a decline in channel activity as a
      result of desensitization, similar to that in atrial cells. 3. Whereas the
      desensitization was almost abolished by not transfecting with the receptor kinase
      or by transfecting with a mutant receptor lacking phosphorylation sites, it was
      only reduced (by approximately 39%) by transfecting with a mutant receptor kinase
      with little/kinase activity. 4. These results suggest that the receptor kinase is
      responsible for desensitization of the muscarinic K+ channel and that this
      involves phosphorylation-dependent and -independent mechanisms.

PMID- 9518697
TI  - Alcohols potentiate the function of 5-HT3 receptor-channels on NCB-20
      neuroblastoma cells by favouring and stabilizing the open channel state.
AB  - 1. 5-HT3 receptor-mediated ion current was recorded from NCB-20 neuroblastoma
      cells using the whole-cell patch-clamp technique. Rapid drug superfusion was used
      to study the mechanism of alcohol potentiation of 5-HT3 receptor function and to
      analyse effects of alcohols on receptor-channel kinetics in detail. 2.
      Trichloroethanol (TCEt) increased in a dose-dependent way the initial slope, 20
      80% rise time and measured desensitization rate of the current induced by low
      concentrations (1-2 microM) of 5-HT. Ethanol (EtOH) and butanol (ButOH) had
      similar effects on the 5-HT3 receptor-induced current. 3. TCEt and ButOH
      decreased the measured desensitization rate of current induced by 10 microM 5-HT,
      a maximally effective concentration of agonist. These alcohols also increased the
      relative amplitude of steady state to peak current induced by 2 or 10 microM 5
      HT, indicating a possible decrease in the intrinsic rate of desensitization. 4.
      TCEt also decreased the deactivation rate of the current activated by 2 microM 5
      HT after a short pulse of agonist application. 5. Current sweeps generated by 1
      microM 5-HT in the presence or absence of 10 mM TCEt or 100 mM EtOH were well
      fitted using a modified standard kinetic model derived from the nicotinic
      acetylcholine receptor. This analysis indicated that potentiation by alcohols
      could be accounted for by increases in the association rate constant coupled with
      decreases in the dissociation and desensitization rate constants. 6. This study
      suggests that alcohols potentiate 5-HT3 receptor-mediated current by both
      increasing the rate of channel activation and stabilizing the open state by
      decreasing the rates of channel deactivation and desensitization.

PMID- 9518698
TI  - Two mechanisms for inward rectification of current flow through the purinoceptor
      P2X2 class of ATP-gated channels.
AB  - 1. The ATP receptor subunit P2X2 was expressed in Xenopus oocytes and human
      embryonic kidney (HEK) 293 cells. ATP-activated currents were studied with two
      electrode voltage clamp recordings from oocytes, whole-cell recordings from HEK
      293 cells, and outside-out patch clamp recordings from both cell types. The
      steady-state current-voltage (I-V) relation showed profound inward rectification
      in all recording configurations. 2. Recordings from outside-out patches
      demonstrated that inward rectification does not require intracellular Mg2+ or
      polyamines, and that inward rectification was present when the same solution was
      used on both sides of the patch. 3. Voltage jump experiments were performed to
      evaluate the voltage dependence of channel gating. After fast voltage jumps,
      instantaneous current jumps were followed by substantial relaxations to the
      steady state. The time course of the current relaxations could be fitted by
      single exponential functions. The instantaneous I-V relation was less inwardly
      rectifying than the steady-state I-V relation; however, it was not linear. 4.
      Single channel recordings indicated that the single channel conductance became
      smaller when the membrane potential became more positive. This decrease could
      quantitatively account for inward rectification of the instantaneous I-V
      relation. 5. We conclude that inward rectification of P2X2 is due to two
      mechanisms: voltage-dependent gating and voltage dependence of the single channel
      conductance.

PMID- 9518699
TI  - Near-visible ultraviolet light induces a novel ubiquitous calcium-permeable
      cation current in mammalian cell lines.
AB  - 1. We studied the immediate and short-term effects of UV light in the near
      visible range at the cellular and membrane level using the whole-cell patch-clamp
      technique in combination with digital fluorescence imaging. 2. Illumination with
      monochromatic UVA light (340-380 nm) induced a sustained non-saturable increase
      in membrane conductance dependent on wavelength and light intensity in several
      different mammalian cell types including RBL, mast, HEK, PC12 and 3T3 cells. 3.
      The current was non-selective for cations and permeable to Ca2+, but was
      inhibited by trivalent cations and was not due to the activation of an endogenous
      ion channel. We termed this novel current ILiNC for light-induced non-selective
      cation current. 4. A similar current was evoked by chemical peroxidants such as
      hydrogen peroxide and tertbutylhydroperoxide, but not by cytosolic oxidized
      glutathione. 5. The free-radical scavengers tocopherol (vitamin E) and ascorbic
      acid (vitamin C) significantly reduced the UV light effect. 6. The generation of
      the current was membrane delimited since it could be induced by the same UVA
      treatment in cell-free membrane patches showing a similar wavelength dependence.
      7. These results suggest that ILiNC is activated by UVA light-induced generation
      of free radicals acting through lipid or protein peroxidation, and may represent
      a ubiquitous mechanism by which Na+ and Ca2+ can enter cells after phototoxic or
      free radical-induced membrane damage.

PMID- 9518700
TI  - Cytosolic and mitochondrial Ca2+ signals in patch clamped mammalian ventricular
      myocytes.
AB  - 1. Ventricular myocytes isolated from ferret or cat were loaded with the
      acetoxymethyl ester form of indo-1 (indo-1 AM) such that approximately 75% of
      cellular indo-1 was mitochondrial. The intramitochondrial indo-1 concentration
      was 0.5-2 mM. 2. Myocytes were also voltage clamped (membrane capacitance, Cm =
      100 pF) and a typical wash-out time constant of cytosolic indo-1 by a patch
      pipette was found to be approximately 300 s. Depolarizations to +110 mV produced
      graded and progressive cellular Ca2+ load via Na(+)-Ca2+ exchange. 3. During
      these relatively slow Ca2+ transients, cell contraction (delta L) paralleled
      fluorescence ratio signals (R) such that delta L could be used as a bioassay of
      cytosolic [Ca2+] ([Ca2+]c), where [Ca2+]CL is the inferred signal which is
      delayed by approximately 200 ms from true [Ca2+]c. 4. In myocytes without Mn2+
      quench, the kinetics of the total cellular indo-1 signal, delta R (including
      cytosolic and mitochondrial components), match delta L during stimulations at low
      basal [Ca2+]i. However, after progressive Ca2+ loading, delta R kinetics deviate
      from delta L dramatically. The deviation can be completely blocked by a potent
      mitochondrial Ca2+ uniport blocker, Ru360. 5. When cytosolic indo-1 is quenched
      by Mn2+, initial moderate stimulation triggers contractions (delta L), but no
      change in indo-1 signal, indicating both the absence of cytosolic Ca(2+)
      sensitive indo-1 and unchanged mitochondrial [Ca2+] (delta [Ca2+]m). Subsequent
      stronger stimulation evoked larger delta L and also delta R. The threshold
      [Ca2+]c for mitochondrial Ca2+ uptake was 300-500 nM, similar to that without
      Mn2+ quench. 6. At high Ca2+ loads where delta [Ca2+]m is detected, the time
      course of [Ca2+]m was different from that of [Ca2+]c. Peak [Ca2+]m after
      stimulation has an approximately 1 s latency with respect to [Ca2+]c, and [Ca2+]m
      decline is extremely slow. 7. Upon a Ca2+ influx which increased [Ca2+]c by 0.4
      microM and [Ca2+]m by 0.2 microM, total mitochondrial Ca2+ uptake was
      approximately 13 mumol (1 mitochondria)-1. 8. With Mn2+ quench of cytosolic indo
      1, there was no mitochondrial uptake of Mn2+ until the point at which
      mitochondrial Ca2+ uptake became apparent. However, after mitochondrial Ca2+
      uptake starts, mitochondria continually take up Mn2+ even during relaxation, when
      [Ca2+]c is low. 9. It is concluded that mitochondria in intact myocytes do not
      take up detectable amounts of Ca2+ during individual contractions, unless resting
      [Ca2+]c exceeds 300-500 nM. At high cell Ca2+ loads and [Ca2+]c, mitochondrial
      Ca2+ transients occur during the twitch, but with much slower kinetics than those
      of [Ca2+]c.

PMID- 9518701
TI  - Cyclic ADP-ribose and calcium-induced calcium release regulate neurotransmitter
      release at a cholinergic synapse of Aplysia.
AB  - 1. Presynaptic injection of cyclic ADP-ribose (cADPR), a modulator of the
      ryanodine receptor, increased the postsynaptic response evoked by a presynaptic
      spike at an identified cholinergic synapse in the buccal ganglion of Aplysia
      californica. 2. The statistical analysis of long duration postsynaptic responses
      evoked by square depolarizations of the voltage-clamped presynaptic neurone
      showed that the number of evoked acetylcholine (ACh) quanta released was
      increased following cADPR injection. 3. Overloading the presynaptic neurone with
      cADPR led to a transient increase of ACh release followed by a depression. 4.
      cADPR injections did not modify the presynaptic Ca2+ current triggering ACh
      release. 5. Ca2+ imaging with the fluorescent dye rhod-2 showed that cADPR
      injection rapidly increased the free intracellular Ca2+ concentration indicating
      that the effects of cADPR on ACh release might be related to Ca2+ release from
      intracellular stores. 6. Ryanodine and 8-amino-cADPR, a specific antagonist of
      cADPR, decreased ACh release. 7. ADP-ribosyl cyclase, which cyclizes NAD+ into
      cADPR, was present in the presynaptic neurone as shown by reverse transcriptase
      polymerase chain reaction experiments. 8. Application of NAD+, the substrate of
      ADP-ribosyl cyclase, increased ACh release and this effect was prevented by both
      ryanodine and 8-amino-cADPR. 9. These results support the view that Ca(2+)
      induced Ca2+ release might be involved in the build-up of the Ca2+ concentration
      which triggers ACh release, and thus that cADPR might have a role in transmitter
      release modulation.

PMID- 9518702
TI  - Extracellular K+ activates a K(+)- and H(+)-permeable conductance in frog taste
      receptor cells.
AB  - 1. The effect of extracellular K+ on membrane currents of bull frog (Rana
      catesbeiana) taste receptor cells (TRCs) was investigated by the patch clamp and
      fast perfusion techniques. Extracellular K+ (2.5-90 mM) increased a TRC resting
      conductance and enhanced both inward and outward whole-cell currents. 2. To
      isolate the inward current activated by external potassium (PA current), TRCs
      were dialysed with 110 mM NMGCl while extracellular NaCl was replaced with NMGCl.
      Under these conditions, the PA current displayed an S-shaped current-voltage (I
      V) curve in the -100 to 100 mV range. Extracellular Rb+ and NH4+, but not Li+,
      Na+ or Cs+, evoked similar currents. 3. The PA current reversal potential (Vr)
      did not follow the equilibrium K+ potential under experimental conditions.
      Therefore, K+ ions were not the only current carriers. The influence of other
      ions on the PA current Vr indicated that the channels involved are permeable to
      K+ and H+ and much less so to Na+, Ca2+ and Mg2+. Relative permeabilities were
      estimated on the basis of the Goldman-Hodgkin-Katz equation as follows: PH:PK:PNa
      = 4000:1:0.04. 4. All I-V curves of the PA current were nearly linear at low
      negative potentials. The slope conductance at these voltages was used to
      characterize the dependence of the PA current on external K+ and H+. The slope
      conductance versus K+ concentration was fitted by the Hill equation. The data
      yielded a half-maximal concentration, K1/2 = 19 +/- 3 mM and a Hill coefficient,
      nH = 1.53 +/- 0.36 (means +/- S.E.M.). 5. The dependence of the mean PA current
      and the current variance on the K+ concentration indicated a rise in the open
      probability of the corresponding channels as extracellular K+ was increased. With
      110 mM KCl in the bath, the single channel conductance was estimated at about 6
      pS. Taken together, the data suggest that extracellular K+ may serve as a ligand
      to activate specific small-conductance cation channels (PA channels). The mean
      number of the PA channels per TRC was estimated as at least 2000. 6.
      Extracellular Ba2+, Cd2+, Co2+, Ni2+ and Cs+ blocked the PA current in a
      potential-dependent manner. The PA current was blocked by Cs+ as quickly as the
      blocker could be applied (approximately 15 ms). The time course of the divalent
      cation block was well fitted by a single exponential function. The time constants
      were estimated at 26.5 +/- 1.9, 41.7 +/- 3.1, 56.1 +/- 4.2 and 370 +/- 18 ms at 1
      mM Cd2+, Co2+, Ni2+ and Ba2+, respectively. The blocker efficiency at negative
      voltages followed the sequence: Cs+ > Cd2+ > Ba2+ > Ni2+ > Co2+. 7. The data
      indicate that protons and divalent blockers act within the PA channel pore and
      that H+ and the divalent ions probably act via similar mechanisms to affect the
      PA current. These observations and the strong pH dependence of the PA current Vr
      suggest that H+ occupation of the PA channel pore leading to interruption of K+
      flux is the main mechanism of the pH dependence of the PA current. 8.
      Extracellular K+ enhanced the sensitivity of isolated TRCs to bath solution
      acidification due to activation of the PA channels. With 10 mM K+ in the bath,
      half-maximal depolarization of the TRCs was observed at pH values of 6.4-6.8. The
      possible role of the PA channels in sour transduction is discussed.

PMID- 9518703
TI  - Non-specificity of chloride channel blockers in rat cerebral arteries: block of
      the L-type calcium channel.
AB  - 1. The effects of chloride channel blockers on pressure-induced constriction,
      K(+)-induced force, and whole-cell calcium channel currents were tested in rat
      cerebral arteries using isobaric and isometric myography, and patch clamp. 2.
      Under isobaric conditions at 75 mmHg, 5-nitro-2-(3-phenylpropylamino)benzoic acid
      (NPPB), a chloride channel blocker, reversibly depressed the myogenic
      constriction with an IC50 of 32.8 +/- 0.52 microM (mean +/- S.E.M., n = 5).
      Blockers of Ca(2+)-activated chloride channels, flufenamic acid (100 microM) and
      9-anthracene chloride (9-AC; 1 mM), and the cystic fibrosis transmembrane
      conductance regulator (CFTR) Cl- channel blocker, glibenclamide (100 microM),
      were without effect in this tissue (n = 3). 3. Under isobaric conditions at 20
      mmHg, 37 degrees C, raising [K+]o to 45 mM induced a constriction which was
      unaffected by 100 microM NPPB (n = 4). In contrast, at 75 mmHg and 18-21 degrees
      C, 100 microM NPPB completely and reversibly blocked a 45 mM K(+)-induced
      constriction (n = 3). 4. Under isometric conditions, NPPB reversibly depressed a
      45 mM K(+)-induced force with an IC50 of 10.0 +/- 0.76 microM (mean +/- S.E.M., n
      = 5). Indanyloxyacetic acid 94 (IAA-94), another chloride channel blocker,
      depressed the K(+)-induced force with an IC50 of 17.0 +/- 1.2 microM (mean +/-
      S.E.M., n = 4). 5. Using whole-cell patch clamp, 100 microM NPPB or 200 microM
      IAA-94 blocked calcium channel currents carried by 10 mM Ba2+ by 79.1 +/- 1.7 and
      39.8 +/- 7.0%, respectively (mean +/- S.E.M., n = 6). 6. In summary, chloride
      channel blockers depress calcium channel currents in rat cerebral arteries, which
      could contribute to a reduction in myogenic contraction.

PMID- 9518704
TI  - Factors determining the efficacy of distal excitatory synapses in rat hippocampal
      CA1 pyramidal neurones.
AB  - 1. A new preparation of the in vitro rat hippocampal slice has been developed in
      which the synaptic input to the distal apical dendrites of CA1 pyramidal neurones
      is isolated. This has been used to investigate the properties of distally evoked
      synaptic potentials. 2. Distal paired-pulse stimulation (0.1 Hz) evoked a
      dendritic response consisting of a pair of EPSPs, which showed facilitation. The
      first EPSP had a rise time (10-90%) of 2.2 +/- 0.05 ms and a half-width of 9.1 +/
      0.13 ms. The EPSPs were greatly reduced by CNQX (10 microM) and the remaining
      component could be enhanced in Mg(2+)-free Ringer solution and blocked by AP5 (50
      microM). In 70% of the dendrites, the EPSPs were followed by a prolonged after
      hyperpolarization (AHP) which could be blocked by a selective and potent GABAB
      antagonist, CGP55845A (2 microM). These results indicate that the EPSPs are
      primarily mediated by non-NMDA receptors with a small contribution from NMDA
      receptors, whereas the AHP is a GABAB receptor-mediated slow IPSP. 3. With
      intrasomatic recordings, the rise time of proximally generated EPSPs (3.4 +/- 0.1
      ms) was half that of distally generated EPSPs (6.7 +/- 0.5 ms), whereas the half
      widths were similar (19.6 +/- 0.8 ms and 23.8 +/- 1 ms, respectively). These
      results indicate that propagation through the proximal apical dendrites slows the
      time-to-peak of distally generated EPSPs. 4. Distal stimulation evoked spikes in
      60% of pyramidal neurones. At threshold, the distally evoked spike always
      appeared on the decaying phase of the dendritic EPSP, indicating that the spike
      is initiated at some distance proximal to the dendritic recording site.
      Furthermore, distally and proximally generated threshold spikes had a similar
      voltage dependency. These results therefore suggest that distally generated
      threshold spikes are primarily initiated at the initial segment. 5. At threshold,
      spikes generated by stimulation of distal synapses arose from the decaying phase
      of the dendritic EPSPs with a latency determined by the time course of the EPSP
      at the spike initiation zone. With maximal stimulation, however, the spikes arose
      directly from the peak of the EPSPs with a time-to-spike similar to the time-to
      peak of subthreshold dendritic EPSPs. Functionally, this means that the effect of
      dendritic propagation can be overcome by recruiting more synapses, thereby
      ensuring a faster response time to distal synaptic inputs. 6. In 42% of the
      neurones in which distal EPSPs evoked spikes, the relationship between EPSP
      amplitude and spike latency could be accounted for by a constant dendritic
      modulation of the EPSP. In the remaining 58%, the change in latency was greater
      than can be accounted for by a constant dendritic influence. This additional
      change in latency is best explained by a sudden shift in the spike initiation
      zone to the proximal dendrites. This would explain the delay observed between the
      action of somatic application of TTX (10 microM) on antidromically evoked spikes
      and distally evoked suprathreshold spikes. 7. The present results indicate that
      full compensation for the electrotonic properties of the main proximal dendrites
      is not achieved despite the presence of Na+ and Ca2+ currents. Nevertheless,
      distal excitatory synapses are capable of initiating spiking in most pyramidal
      neurones, and changes in EPSP amplitude can modulate the spike latency.
      Furthermore, even though the primary spike initiation zone is in the initial
      segment, the results suggest that it can move into the proximal apical dendrites
      under physiological conditions, which has the effect of further shortening the
      response time to distal excitatory synaptic inputs.

PMID- 9518705
TI  - Properties and glial origin of osmotic-dependent release of taurine from the rat
      supraoptic nucleus.
AB  - 1. Taurine, prominently concentrated in glial cells in the supraoptic nucleus
      (SON), is probably involved in the inhibition of SON vasopressin neurones by
      peripheral hypotonic stimulus, via activation of neuronal glycine receptors. We
      report here the properties and origin of the osmolarity-dependent release of
      preloaded [3H]taurine from isolated whole SO nuclei. 2. Hyposmotic medium induced
      a rapid, reversible and dose-dependent increase in taurine release. Release
      showed a high sensitivity to osmotic change, with a significant enhancement with
      less than a 5% decrease in osmolarity. Hyperosmotic stimulus decreased basal
      release. 3. Evoked release was independent of extracellular Ca2+ and Na+, and was
      blocked by the Cl- channel blockers DIDS (4,4'-diisothiocyanatostilbene-2,2'
      disulphonic acid) and DPC (N-phenylanthranilic acid), suggesting a diffusion
      process through volume-sensitive Cl- channels. 4. Evoked release was transient
      for large osmotic reductions (> or = 15%), probably reflecting regulatory volume
      decrease (RVD). However, it was sustained for smaller changes, suggesting that
      taurine release induced by physiological variations in osmolarity is not linked
      to RVD. 5. Basal and evoked release were strongly inhibited by an incubation of
      the tissue with the glia-specific toxin fluorocitrate, but were unaffected by a
      neurotoxic-treatment with NMDA, demonstrating the glial origin of the release of
      taurine in the SON. 6. The high osmosensitivity of taurine release suggests an
      important role in the osmoregulation of the SON function. These results
      strengthen the notion of an implication of taurine and glial cells in the
      regulation of the whole-body fluid balance through the modulation of vasopressin
      release.

PMID- 9518707
TI  - Type I and II models of diabetes produce different modifications of K+ currents
      in rat heart: role of insulin.
AB  - 1. Several K+ currents were measured and compared in enzymatically dispersed
      ventricular myocytes from control and diabetic rats. 2. Diabetic conditions were
      established either with a single intravenous injection of streptozotocin (STZ,
      100 mg kg-1; 6-14 days duration) or by feeding with a fructose-enriched diet for
      4-10 weeks. Both groups became hyperglycaemic, with the former having decreased
      and the latter having elevated levels of plasma insulin. These conditions
      therefore mimic type I (insulin-dependent) and type II (non-insulin-dependent)
      diabetes mellitus, respectively. 3. As reported previously, a Ca(2+)-independent
      transient outward K+ current, I(t), was attenuated in the type I model. This was
      not observed in the type II model. The two models differed greatly in the changes
      observed in a quasi-steady-state K+ current denoted Iss. In the STZ model Iss was
      substantially attenuated, whereas in the fructose-fed model it was augmented. In
      both models, the background inwardly rectifying current, IK1, was unchanged.
      Concomitantly, there was a substantial prolongation of the action potential in
      the STZ model but not in the fructose-fed model. 4. Incubation of control
      myocytes with insulin (100 nM) for 5-9 h caused a significant augmentation of
      Iss, with no effect on I(t) or on IK1. Incubation of myocytes from STZ-diabetic
      rats with insulin reversed the attenuation of I(t), but not of Iss. 5. The effect
      of insulin was not blocked by wortmannin, an inhibitor of phosphatidylinositol 3
      kinase. However, inhibition of the mitogen-activated protein kinase pathway with
      PD98059 prevented restoration of I(t). Insulin action on I(t) may therefore
      involve changes in transcription or expression of channel proteins, rather than
      changes in cellular metabolism.

PMID- 9518706
TI  - Glycine and GABAA receptor-mediated synaptic transmission in rat substantia
      gelatinosa: inhibition by mu-opioid and GABAB agonists.
AB  - 1. Bicuculline-sensitive and strychnine-sensitive inhibitory postsynaptic
      currents (IPSCs) could be evoked in neurones of the rat substantia gelatinosa of
      the spinal trigeminal nucleus pars caudalis. 2. Spontaneous tetrodotoxin (TTX)
      insensitive-mediated miniature IPSCs (mIPSCs) blocked by strychnine or
      bicuculline were also present in many neurones. The decay of the glycine receptor
      mediated mIPSCs was fitted by a single exponential, whereas the decay of the
      GABAA receptor-mediated mIPSCs could in some instances be fitted by a single
      exponential, but in other instances required two exponentials. 3. An increase in
      baseline current noise developed during the course of the recording. This noise
      was abolished by strychnine (1 microM) but was insensitive to bicuculline (10
      microM), TTX (0.5 microM), [D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (DAMGO, 1
      microM) or baclofen (30 microM). The single-channel conductance underlying the
      noise was estimated to be 21 pS. 4. The mu-opioid agonist DAMGO (1-10 microM)
      reduced the amplitude of the evoked glycine receptor-mediated IPSC and the evoked
      GABAA receptor-mediated IPSC. The mu-opioid antagonist D-Phe-Cys-Tyr-D-Trp-Arg
      Thr-Pen-Thr-NH2 (CTAP, 1 microM) reversed the DAMGO inhibition. 5. The GABAB
      agonist baclofen (30 microM) reduced the amplitude of the evoked glycine receptor
      mediated IPSC and the GABAA receptor-mediated IPSC. The inhibition was reversed
      by the selective GABAB antagonist 3-N[1-(S)-(3,4-dichlorophenyl)ethyl]amino- 2
      (S)-hydroxypropyl-P-benzyl-phosphinic acid (CGP 55845A, 1 microM). 6. Both DAMGO
      and baclofen reduced the frequency of glycine and GABAA receptor-mediated mIPSCs
      without affecting average amplitude, and increased the percentage of failures of
      the evoked glycine and GABAA receptor-mediated IPSCs, suggesting a presynaptic
      site of action.

PMID- 9518708
TI  - Age-dependent changes in myosin composition correlate with enhanced economy of
      contraction in guinea-pig hearts.
AB  - 1. The composition of myosin heavy chains (MHCs) was investigated in young (1- to
      8-week-old) and mature (9- to 26-week-old) guinea-pigs using two monoclonal
      antibodies directed specifically against alpha-MHC and beta-MHC. In addition,
      maximum force and the rate of ATP consumption during isometric contraction were
      measured in chemically skinned trabeculae taken from the same hearts. 2. An age
      dependent shift in the MHC composition was found. The alpha-MHC fraction
      decreased from 0.17 +/- 0.02 (mean +/- S.E.M.; n = 24) in young to 0.04 +/- 0.01
      (n = 43) in mature hearts. This shift was correlated with a decrease in tension
      cost (i.e. ATP consumption per second per trabecula volume/force per cross
      sectional area) from 4.1 +/- 0.2 mmol kN-1 m-1 s-1 (n = 23) in young to 2.5 +/-
      0.1 mmol kN-1 m-1 s-1 (n = 57) in mature hearts. 3. From the results it follows
      that the slow beta-MHC isoform, which predominates in hearts of mature guinea
      pigs, is about 5 times more economical than the fast alpha-MHC isoform. Calcium
      sensitivity of force and ATP consumption decreased with age, but stabilized
      within a few weeks after birth. The pronounced dependence of cardiac energetics
      on MHC composition should be taken into account in long-term studies of cardiac
      overload.

PMID- 9518709
TI  - Changes in the maximum speed of shortening of frog muscle fibres early in a
      tetanic contraction and during relaxation.
AB  - 1. Isotonic shortening velocities at very light loads were examined in single
      fibres of the anterior tibialis muscle of the frog, Rana temporaria, using load
      clamp recording and slack tests (temperature, 1-3 degrees C; initial sarcomere
      length, 2.25 microns). 2. Shortening velocities at very light loads (force-clamp
      recording) were found to be higher early in the rise of a tetanic contraction
      than during the plateau of the contraction. The upper limit of the load at which
      there was elevated shortening velocity early in the contraction was 1.5-5.4% of
      the maximum tetanic tension (Fo) depending on the particular fibre. 3. The
      maximum shortening velocity determined using the slack test method (Vo) was as
      much as 30% greater early in a contraction than at the tetanic plateau. Vo was
      elevated above the plateau level up to about 30 ms after the end of the latent
      period, which is equivalent to the time required for the force in an isometric
      contraction to rise to about 30% of Fo. Vo is depressed below the plateau value
      during relaxation at the cessation of stimulation. 4. Stimulation studies show
      that the cross-bridge model of Huxley (1957) predicts the maximum shortening
      velocity to be greater early in a contraction, when new actin binding sites are
      becoming activated and new cross-bridge connections are being formed rapidly,
      than during steady-state contraction. The elevated shortening velocity in the
      model is a consequence of new cross-bridges being formed in the pulling
      configuration, and there being a delay before the newly added bridges are dragged
      beyond their equilibrium position so they begin to retard shortening. The model
      also predicts that maximum shortening velocity should be depressed below the
      plateau level during early relaxation as cross-bridge binding sites are rapidly
      removed from the active population.

PMID- 9518710
TI  - Na(+)-K+ pump cycle during beta-adrenergic stimulation of adult rat cardiac
      myocytes.
AB  - 1. The mechanisms underlying the increase in Na(+)-K+ pump current (Ip) caused by
      adrenergic stimulation were investigated in cultured adult rat cardiac myocytes
      using the whole-cell patch-clamp technique at 31-33 degrees C. 2. In myocytes
      perfused internally with 50 mM Na+ (0 K+i, 20 nM Ca2+, caesium aspartate
      solution) and externally with 5.4 mM K+o, noradrenaline (NA) and isoprenaline
      (Iso) (1-50 microM) stimulated Ip by 40-45%. 3. Na(+)-dependent transient Ip
      measurements with 0 mM K+i and 0 mM K+o revealed no change in the total charge
      transferred by the Na(+)-K+ pump during the conformational change, suggesting
      that the pump site density was not changed by adrenergic stimulation (2630 +/-
      370 pumps micron-2 in control and 2540 +/- 190 pumps micron-2 in the presence of
      10 microM NA). 4. With saturating Na+i or K+o (150 and 15-20 mM, respectively),
      Ip was still stimulated by NA and Iso. Thus, there was no indication that
      adrenergic activation of the Na(+)-K+ pump was mediated by accumulation of Na+i
      and K+o or changes in the Na(+)-K+ pump affinity for Na+i and K+o. 5. Both Ip and
      its increase under adrenergic stimulation were found to depend on [K+]i. While
      steady-state Ip decreased from 2.2 +/- 0.1 to 1.2 +/- 0.1 pA pF-1 (P < 0.05), the
      stimulation of Ip by 10 microM Iso increased from 0.38 +/- 0.04 to 0.67 +/- 0.06
      pA pF-1 (P < 0.05) with an increase in [K+]i from 0 to 100 mM. 6. Under
      conditions that cause the Ip-Vm (membrane potential) relationship to express a
      positive slope ([Na+]o, 150 mM; [K+]o, 5.4 mM) or a negative slope ([Na+]o, 0;
      [K+]o, 0.3 mM) Iso stimulated Ip with no change in the shape of Ip-Vm curves.
      Thus, adrenergic stimulation of the Na(+)-K+ pump was not due to an alteration of
      voltage-dependent steps of the pump cycle. 7. Simulation of these data with a six
      step model of the Na(+)-K+ pump cycle suggested that in rat ventricular myocytes
      a signal from adrenergic receptors increased the Na(+)-K+ pump rate by modulating
      the rate of K+ de-occlusion and release by the pump.

PMID- 9518711
TI  - Arachidonic acid increases cerebral microvascular permeability by free radicals
      in single pial microvessels of the anaesthetized rat.
AB  - 1. We have investigated the permeability-increasing effect of arachidonic acid on
      pial venular capillaries in vivo using the single microvessel occlusion
      technique. 2. Permeability to Lucifer Yellow dye (476 Da) increased dose
      dependently when arachidonic acid was applied focally to the abluminal surface of
      the vessels. This was completely reversible at all but the highest dose. The
      permeability increase was 1.65 x 10(-6) +/- 0.247 x 10(-6) cm s-1 (mean +/-
      S.E.M.) at 0.25 mM, 3.53 x 10(-6) +/- 0.872 x 10(-6) cm s-1 at 0.5 mM, 12.61 x
      10(-6) +/- 3.44 x 10(-6) cm s-1 at 1 mM and 18.46 x 10(-6) +/- 5.90 x 10(-6) cm s
      1 at 2 mM arachidonic acid. There was a similar reversible dose-dependent
      permeability increase to eicosapentaenoic acid. 3. These permeability increases
      could be prevented by co-application of a mixture of the antioxidants superoxide
      dismutase and catalase (30 and 100 U ml-1), or by the iron chelator
      desferrioxamine (100 microM). 4. The permeability increases were also prevented
      by the cyclooxygenase and 5-lipoxygenase blockers indomethacin (100 microM) and
      nordihydroguariaretic acid (100 microM), respectively, when applied together, but
      not singly. 5. It was concluded that the permeability response to arachidonic
      acid depends on the formation of free radicals and subsequent lipid peroxidation.

PMID- 9518713
TI  - Localization of cAMP- and aldosterone-induced K+ secretion in rat distal colon by
      conductance scanning.
AB  - 1. Aldosterone- and adrenaline-induced K+ secretion were investigated in rat late
      distal colon using conductance scanning and Ussing chamber techniques. K+
      secretion was unmasked by the K+ channel blocker tetraethylammonium (TEA).
      Electrogenic Na+ absorption was inhibited by amiloride. Rb+ net fluxes
      consistently measured about 80% of K+ secretion estimated using change in short
      circuit current (delta ISC) measurements. 2. Partial block of K+ absorption by
      mucosal ouabain did not change TEA-sensitive K+ secretion. Thus, K+ absorption
      and K+ secretion are not coupled. 3. Additivity of Rb+ fluxes as well as delta
      ISC caused by 3 nM aldosterone (6 h in vitro incubation) and, subsequently,
      adrenaline suggested additivity of aldosterone-induced and cAMP-mediated K+
      secretion in the presence of amiloride. 4. Conductance scanning under control
      conditions revealed a small TEA-sensitive K+ conductivity in surface epithelium
      (0.3 +/- 0.2 mS cm-2) but not in crypts, as well as a small basal K+ secretion in
      surface epithelium (delta ISC = 0.3 mumol h-1 cm-2), which increased during sham
      incubation. 5. Aldosterone (3 nM, 6 h in vitro incubation) resulted, after
      correction for the basal K+ secretion, in a K+ secretion of delta ISC = 0.9 mumol
      h-1 cm-2. Aldosterone induced a TEA-sensitive conductivity of 1.1 +/- 0.3 mS cm-2
      in surface epithelium, but not in crypts. 6. Adrenaline (5 microM) caused, in
      fresh tissue, a K+ secretion of delta ISC = 1.2 mumol h-1 cm-2 and equal
      conductivity changes in crypts (0.7 +/- 0.2 mS cm-2) and surface epithelium (0.7
      +/- 0.1 mS cm-2). 7. We conclude that K+ secretion induced by aldosterone in
      physiological concentration is restricted to surface epithelium, whereas cAMP
      mediated K+ secretion is located equally in crypts and surface epithelium.

PMID- 9518712
TI  - Extrinsic neural control of nitric oxide synthase expression in the myenteric
      plexus of rat jejunum.
AB  - 1. The role of extrinsic innervation in the expression of nitric oxide synthase
      (NOS) in the myenteric plexus remains unknown. In this study, we investigated the
      effect of extrinsic denervation on NOS expression in rat jejunum. 2. NG-nitro-L
      arginine methyl ester (L-NAME)-sensitive non-adrenergic, non-cholinergic (NANC)
      relaxations induced by transmural nerve stimulation were significantly increased
      in muscle strips obtained from rats treated with splanchnic ganglionectomy or 6
      hydroxydopamine (6-OH-dopamine). Truncal vagotomy or treatment of the coeliac
      ganglia with capsaicin did not significantly affect NANC relaxations. 3. The
      number of NOS-immunopositive cells in the myenteric plexus was significantly
      increased in tissues obtained from rats treated with splanchnic ganglionectomy or
      6-OH-dopamine. 4. Western blot analysis and Northern blot analysis showed a
      significant increase in the density of the immunoreactive NOS band and the NOS
      mRNA band, respectively, of the tissues obtained from rats treated with
      splanchnic ganglionectomy or 6-OH-dopamine. 5. Truncal vagotomy or treatment of
      the coeliac ganglia with capsaicin did not significantly affect the density of
      NOS band or NOS mRNA band. 6. It is concluded that neuronal NOS expression in the
      myenteric plexus is independent of vagus nerve and is negatively regulated by the
      splanchnic nerves in the rat small intestine.

PMID- 9518714
TI  - The hypoxic response of neurones within the in vitro mammalian respiratory
      network.
AB  - 1. The transverse brainstem slice preparation containing the pre-Botzinger
      complex (PBC) was used in mice to study developmental changes of the response of
      the in vitro respiratory network to hypoxia. This preparation generates at
      different postnatal stages (postnatal days (P) 0-22) spontaneous rhythmic
      activity in hypoglossal (XII) rootlets that occur in synchrony with periodic
      bursts of neurones in the PBC. 2. In slices from P0-4 mice, hypoxia did not
      significantly affect the amplitude of rhythmic synaptic drive potentials in four
      of five inspiratory neurones. Hypoxia reduced, but did not suppress, the
      amplitude of synaptic drive potentials in only one inspiratory neurone. Spike
      discharge and phasic 'inspiratory' hyperpolarizations of six expiratory neurones
      were suppressed during hypoxia revealing a phasic 'inspiratory' depolarization.
      3. The coupling between rhythmic activity in PBC neurones and XII bursts occurred
      under control conditions in preparations from P0-4 mice in a 1:1 manner (n = 11)
      and from mice older than P5 in a 3:1 manner (n = 9). During hypoxia, PBC and XII
      activity were linked in a 1:1 manner in all slices. 4. In six of fourteen
      inspiratory PBC neurones, the amplitude of synaptic drive potentials of slices
      from mice older than P8 was increased during the period of augmentation, reduced
      during the period of depression and suppressed during a hypoxic response which we
      refer to as central apnoea. Augmentation led to a weak-to-moderate membrane
      depolarization which on average was 4.8 +/- 3.7 mV. This depolarization was
      followed by a hyperpolarization of 6.2 +/- 4.1 mV only in four inspiratory
      neurones. In the majority of neurones (n = 9), however, membrane depolarization
      remained stable and was not followed by hyperpolarization. In expiratory neurones
      (n = 12) from this age group hypoxia suppressed phasic hyperpolarizations that
      occurred in synchrony with XII bursts. As similarly seen in inspiratory neurones,
      membrane potentials were depolarized by 5.1 +/- 4.1 mV during the period of
      hypoxic augmentation. 5. The hypoxic response of respiratory neurones within the
      pre-Botzinger complex resembles the response of neurones that were previously
      described under in vivo conditions. Thus we conclude that the 'transverse
      rhythmic slice' is a good model for studying the hypoxic response of the
      respiratory network under in vitro conditions.

PMID- 9518715
TI  - Shortening-induced force depression in human adductor pollicis muscle.
AB  - 1. The effects of single isovelocity shortening contractions on force production
      of the electrically stimulated human adductor pollicis muscle were investigated
      in seven healthy male subjects. 2. Redeveloped isometric force immediately
      following isovelocity shortening was always depressed compared with the isometric
      force recorded at the same muscle length but without preceding shortening. The
      maximal isometric force deficit (FD) was (mean +/- S.E.M.) 37 +/- 2% after 38 deg
      of shortening at 6.1 deg s-1. 3. The FD was positively correlated with angular
      displacement (r2 > 0.98) and decreased with increasing velocity of the shortening
      step. Stimulation at 20 Hz instead of 50 Hz reduced absolute force levels during
      the contractions to about 73% and the FD was decreased to a similar extent.
      Eighty-nine per cent of the velocity-related variation in the FD could be
      explained by the absolute force levels during shortening. 4. FD was largely
      abolished by allowing the muscle to relax briefly (approximately 200 ms), a time
      probably too short for significant metabolic recovery. 5. At all but the highest
      velocities there was a linear decline in force during the latter part of the
      isovelocity shortening phase, suggesting that the mechanisms underlying FD were
      active during shortening. 6. Our results show that shortening-induced force
      deficit is a significant feature of human muscle working in situ and is
      proportional to the work done by the muscle-tendon complex. This finding has
      important implications for experimental studies of force-velocity relationships
      in the intact human.

PMID- 9518716
TI  - Energy metabolism of the gastrocnemius and soleus muscles during isometric
      voluntary and electrically induced contractions in man.
AB  - 1. Phosphocreatine (PCr) and intracellular pH detected by 31P NMR in the
      gastrocnemius and soleus muscles were evaluated in order to compare the anaerobic
      ATP costs of voluntary and electrically induced exercise. Continuous isometric
      contraction at 40% of maximum force and repeated isometric contractions at
      approximately 75% of maximum force (contraction plus relaxation period of 0.5 s
      plus 2 s) were studied. 2. Anaerobic ATP turnover in soleus and gastrocnemius
      muscles was slower during continuous voluntary contraction than during continuous
      electrically induced contraction (0.36 +/- 0.04 versus 0.63 +/- 0.05 mmol (kg wet
      wt)-1 s-1, P < 0.05, in soleus; 0.19 +/- 0.03 versus 1.04 +/- 0.04 mmol (kg wet
      wt)-1 s-1, P < 0.001, in gastrocnemius). 3. There was no significant difference
      in anaerobic ATP turnover between voluntary and electrically induced exercise
      when repeated brief contractions were performed (0.22 +/- 0.05 and 0.30 +/- 0.04
      mmol (kg wet wt)-1 s-1, respectively, for the soleus muscle and 0.57 +/- 0.03 and
      0.66 +/- 0.07 mmol (kg wet wt)-1 s-1, respectively, for the gastrocnemius
      muscle). 4. During continuous voluntary contraction, in contrast to continuous
      stimulated contraction, anaerobic ATP turnover was slower (P < 0.05) in the
      gastrocnemius than in the soleus muscle, which also showed a higher
      electromyogram amplitude (41.1 +/- 1.1% of maximum) than the medial gastrocnemius
      muscle (21.4 +/- 3.6% of maximum, P < 0.001). 5. Anaerobic ATP turnover was
      faster (P < 0.05) in the gastrocnemius than in the soleus muscle during brief
      voluntary and brief electrically induced contractions. 6. The results show that
      the anaerobic ATP costs were higher for electrically induced exercise than for
      voluntary exercise when continuous submaximal contraction was performed but not
      when brief high-intensity contractions were performed. The gastrocnemius muscle
      contributes to total force production relatively less than the soleus muscle
      during continuous voluntary plantar flexion at 40% of the maximum voluntary
      contraction.

PMID- 9518717
TI  - Vasodilator component in sympathetic nerve activity destined for the skin of the
      dorsal foot of mildly heated humans.
AB  - 1. Skin sympathetic nerve activity (SSNA) was recorded in seven male subjects
      from the peroneal nerve by microneurography, and the temporal correspondence of
      spontaneously occurring SSNA bursts with vasodilatation and sweating responses on
      the dorsal foot was studied during a mild body heating at rest. 2. Some SSNA
      bursts were followed by a sweat expulsion with a latency of 2.4 +/- 0.4 s, and
      some bursts by a transient vasodilatation with a latency of 2.2 +/- 0.4 s (means
      +/- S.D.). SSNA bursts followed both by a sweat expulsion and by a vasodilatation
      response (Type 1), those followed only by a sweat expulsion (Type 2) and those
      followed only by a vasodilatation, response (Type 3) were 70%, 10% and 1% of the
      total bursts examined, respectively. 3. For Type 1 bursts, there was a
      significant, but weak linear relationship among the burst amplitude, the
      amplitude of the corresponding vasodilatation and the amplitude of the
      corresponding sweat expulsion. 4. It was concluded that SSNA contains
      vasodilatory activity which is synchronous with sudomotor nerve activity. The
      results suggest that such vasodilatory activity contributes to sustaining the
      sweat gland function by supplying sufficient blood.

PMID- 9518718
TI  - Human calf precapillary resistance decreases in response to small cumulative
      increases in venous congestion pressure.
AB  - 1. We studied human lower limbs to test the hypothesis that the application of
      small cumulative venous congestion pressure steps is associated with a reduction
      in precapillary resistance. 2. Strain gauge plethysmography was performed on
      twenty-one young subjects (22.7 +/- 0.6 years). At each of the small cumulative
      pressure steps, limb blood flow was estimated from the initial slope of the
      volume response to transient (10 s duration) elevations of venous congestion
      pressure to 90 mmHg, after which the congestion pressure was returned to the
      previous value. The blood flow at each pressure was also expressed as a
      percentage of the initial control value. Peak tibial arterial blood flux was
      assessed, in four of the subjects, using colour duplex ultrasonography and the
      same congestion pressure protocol. 3. We used Darcy's Law to predict the limb
      arterial blood flow and blood flux at each venous congestion pressure, assuming
      that both mean arterial blood pressure and precapillary resistance remained
      constant. 4. The mean +/- S.E.M. control arterial blood flow at the lowest venous
      congestion pressure, 4.8 +/- 0.1 mmHg, was 2.77 +/- 0.18 ml min-1 (100 ml)-1. At
      the highest venous congestion pressure, 59.2 +/- 0.2 mmHg, arterial blood flow
      was 2.45 +/- 0.35 ml min-1 (100 ml)-1 (121.6 +/- 16.9% of the initial value).
      This did not differ significantly from the initial control value, but was
      significantly greater than the predicted value of 0.77 +/- 0.13 ml min-1 (100 ml)
      1 (28.6 +/- 2.1% of the initial value) calculated assuming constant resistance
      and sustained mean arterial pressure. The tibial arterial peak blood flux at 58.3
      mmHg venous congestion pressure was 102.2 +/- 2.3% of the control value, which
      was significantly greater than the predicted 17.2 +/- 1.3% of control, calculated
      for this pressure, assuming constant resistance and sustained mean arterial
      pressure. 5. Our data show that lower limb arterial blood flow is sustained when
      venous congestion pressure is raised using small cumulative steps, even at
      congestion pressures approaching mean arterial blood pressure. These data support
      the notion that precapillary resistance is influenced by signals generated at the
      microvascular and post microvascular levels and transmitted via the endothelium.

PMID- 9518719
TI  - Exercise-induced arterial hypoxaemia in healthy young women.
AB  - 1. We questioned whether exercise-induced arterial hypoxaemia (EIAH) occurs in
      healthy active women, who have smaller lungs, reduced lung diffusion, and lower
      maximal O2 consumption rate (VO2,max) than age- and height-matched men. 2. Twenty
      nine healthy young women with widely varying fitness levels (VO2,max, 57 +/- 6 ml
      kg-1 min-1; range, 35-70 ml kg-1 min-1; or 148 +/- 5%; range, 93-188% predicted)
      and normal resting lung function underwent an incremental treadmill test to
      VO2,max during the follicular phase of their menstrual cycle. Arterial blood
      samples were taken at rest and near the end of each workload. 3. Arterial PO2
      (Pa,O2) decreased > 10 mmHg below rest in twenty-two of twenty-nine subjects at
      VO2,max (Pa,O2, 77.5 +/- 0.9 mmHg; range, 67-88 mmHg; arterial O2 saturation
      (Sa,O2), 92.3 +/- 0.2%; range, 87-94%). The remaining seven subjects maintained
      Pa,O2 within 10 mmHg of rest. Pa,O2 at VO2,max was inversely related to the
      alveolar to arterial O2 difference (A-aDO2) (r = -0.93; 35-52 mmHg) and to
      arterial PCO2 (Pa,CO2) (r = -0.62; 26-39 mmHg). 4. EIAH was inversely related to
      VO2,max (r = -0.49); however, there were many exceptions. Almost half of the
      women with significant EIAH had VO2,max within 15% of predicted normal values
      (VO2,max, 40-55 ml kg-1 min-1); among subjects with very high VO2,max (55-70 ml
      kg-1 min-1), the degree of excessive A-aDO2 and EIAH varied markedly (e.g. A
      aDO2, 30-50 mmHg; Pa,O2, 68-91 mmHg). 5. In the women with EIAH at VO2,max, many
      began to experience an excessive widening of their A-aDO2 during moderate
      intensity exercise, which when combined with a weak ventilatory response, led to
      a progressive hypoxaemia. Inactive, less fit subjects had no EIAH and narrower A
      aDO2 when compared with active, fitter subjects at the same VO2 (40-50 ml kg-1
      min-1). 6. These data demonstrate that many active healthy young women experience
      significant EIAH, and at a VO2,max that is substantially less than those in their
      active male contemporaries. The onset of EIAH during submaximal exercise, and/or
      its occurrence at a relatively low VO2,max, implies that lung structure/function
      subserving alveolar to arterial O2 transport is abnormally compromised in many of
      these habitually active subjects.

PMID- 9518720
TI  - Ca2+-induced Ca2+ release: physiological experiments on a new level.

PMID- 9518721
TI  - Synchronization of somato-sympathetic outflows during exercise: role for a spinal
      rhythm generator.

PMID- 9518723
TI  - Non-genomic inhibition of human P2X7 purinoceptor by 17beta-oestradiol.
AB  - 1. Effects of oestrogen on the current evoked by ATP and benzoylbenzoyl ATP
      (BzATP) in CV-1 monkey kidney cells transformed by SV 40 (COS cells) expressing
      the human P2X7 (hP2X7) purinoceptor were studied using standard patch-clamp
      techniques. 2. 17beta-Oestradiol rapidly and reversibly inhibited the whole-cell
      hP2X7 receptor cation current. This inhibitory action resulted in a rightward
      shift of the dose-response curve to ATP and BzATP in the presence of
      physiological as well as low divalent cation concentrations. 3. The inhibitory
      effect of 17beta-oestradiol on the BzATP- or ATP-induced cation current was
      concentration dependent. The half-maximal inhibition was obtained with 3 microM
      17beta-oestradiol. Progesterone and 17alpha-oestradiol had almost no effect on
      the hP2X7 receptor cation current. 4. The inhibition of the hP2X7 receptor cation
      current by 17beta-oestradiol did not depend on the membrane potential. 17beta
      Oestradiol added to the extracellular side of outside-out patches inhibited BzATP
      activated single-channel currents. 5. Activation of the hP2X7 receptor in both
      COS and U937 (human macrophage) cells did not induce the formation of large non
      specific pores. 6. Since COS cells do not express endogenous nuclear oestrogen
      receptor, this study shows that, at pharmacological concentrations, 17beta
      oestradiol inhibited the hP2X7 receptor cation channel in a non-genomic manner.

PMID- 9518722
TI  - Structure and function of voltage-gated sodium channels.
AB  - 1. Sodium channels mediate fast depolarization and conduct electrical impulses
      throughout nerve, muscle and heart. This paper reviews the links between sodium
      channel structure and function. 2. Sodium channels have a modular architecture,
      with distinct regions for the pore and the gates. The separation is far from
      absolute, however, with extensive interaction among the various parts of the
      channel. 3. At a molecular level, sodium channels are not static: they move
      extensively in the course of gating and ion translocation. 4. Sodium channels
      bind local anaesthetics and various toxins. In some cases, the relevant sites
      have been partially identified. 5. Sodium channels are subject to regulation at
      the levels of transcription, subunit interaction and post-translational
      modification (notably glycosylation and phosphorylation).

PMID- 9518724
TI  - Four novel myosin heavy chain transcripts define a molecular basis for muscle
      fibre types in Rana pipiens.
AB  - 1. Differential expression of myosin heavy chain (MHC) isoforms dramatically
      affects mechanical and energetic properties of skeletal muscle fibre types. As
      many as five different fibre types, each with different mechanical properties,
      have been reported in frog hindlimb muscles. However, only two frog MHC isoforms
      have previously been detected by SDS-PAGE and only one adult hindlimb MHC isoform
      has been cloned. 2. In the present study, four different fibre types (type 1,
      type 2, type 3 and tonic) were initially identified in adult Rana pipiens
      anterior tibialis muscle based on myosin ATPase histochemistry, size and
      location. Each fibre type exhibited unique reactivity to a panel of MHC
      monoclonal antibodies. Single fibre analysis using SDS-PAGE revealed that MHCs
      from immunohistochemically defined type 1, type 2 and type 3 fibres ran as three
      distinct isoform bands, while MHC of tonic fibres co-migrated with type 1 MHC.
      The combined data from immunohistochemistry and SDS-PAGE suggests that Rana fibre
      types are composed of four different MHCs. 3. Four novel MHC cDNAs were cloned
      and expression of the corresponding transcripts was measured in single immuno
      identified fibres using specific polymerase chain reaction (PCR) primer pairs.
      Each of the four transcripts was found to be primarily expressed in a different
      one of the four fibre types. 4. Coexpression of MHC isoforms was observed only
      between types 1/2 and types 2/3 at both the protein and mRNA level. 5. These data
      provide a molecular basis for differentiation between frog fibre types and permit
      future molecular studies of MHC structure/function and gene regulation in this
      classic physiological system. 6. Comparison of sequence homology among amphibian,
      avian and mammalian MHC families supports the concept of independent evolution of
      fast MHC genes within vertebrate classes subsequent to the
      amphibian/avian/mammalian radiation.

PMID- 9518725
TI  - Protein kinases modulate two glycine currents in salamander retinal ganglion
      cells.
AB  - 1. Protein kinase modulation of glycine-activated currents was examined in
      acutely dissociated ganglion cells from tiger salamander retina using whole-cell
      voltage-clamp techniques. 2. Glycine (100 microM) induced an outward chloride
      current in cells clamped at 0 mV. Co-application of 50 microM forskolin made the
      glycine-induced current more transient. The combination of forskolin and glycine
      reduced the later portion of current response without changing the initial peak
      amplitude. 3. 3-Isobutyl-1-methylxanthine (IBMX) or 8-bromoadenosine 3',5'-cyclic
      monophosphate (8-Br-cAMP) produced effects similar to those of forskolin. H-89, a
      protein kinase A (PKA) inhibitor, blocked the effect of forskolin. 4. A protein
      kinase C (PKC) activator, OAG (1-oleoyl-2-acetyl-sn-glycerol), also made the
      glycine response more transient. Unlike PKA analogues, OAG enhanced the glycine
      peak response without changing the glycine late response. OAG effects were
      blocked by 1 microM GF-109203X, a PKC inhibitor. 5. Nanomolar concentrations of
      strychnine selectively blocked the fast phase of the glycine current and reversed
      the effect of OAG, but not that of forskolin. Conversely, forskolin occluded the
      effect of 5,7-dichlorokynurenic acid, which selectively suppresses the late phase
      of the glycine current. The action of OAG was not blocked by 5,7
      dichlorokynurenic acid. 6. Thus, through a differential modulation, both protein
      kinase A and C shorten the decay time of the glycine current. PKA suppresses the
      slow component, while PKC potentiates the fast component.

PMID- 9518726
TI  - ATP and glutamate are released from separate neurones in the rat medial habenula
      nucleus: frequency dependence and adenosine-mediated inhibition of release.
AB  - 1. ATP and glutamatergic synaptic currents were compared in slices of rat medial
      habenula nucleus using whole-cell patch-clamp techniques. 2. In most cells low
      voltage stimulation resulted in glutamatergic responses and not purinergic
      responses. In five cells where ATP currents could be stimulated with low
      voltages, wash out of glutamate antagonists did not reveal evoked glutamate
      currents. Spontaneous glutamate currents confirmed washout of antagonist. 3.
      Modulation of release probability of glutamate and ATP, assessed by changes in
      failure rate of synaptic currents, was compared under conditions of different
      stimulation frequencies and in the presence of adenosine agonists and
      antagonists. 4. ATP release, but not glutamate release, was shown to be modulated
      by increased stimulation frequency which resulted in inhibition of ATP release
      via A2-like adenosine receptors. A1 receptors caused inhibition of both ATP and
      glutamate release. 5. Endogenous adenosine inhibited glutamate release via A1
      receptors but only inhibited ATP release via A2-like receptors. 6. Attempts to
      inhibit the degradation of ATP to adenosine did not alter the frequency
      dependence of the failure rate. 7. We conclude, from the direct demonstration and
      from the differences in pharmacology and frequency dependence of the modulation
      of release, that ATP and glutamate responses are due to release from separate
      neurones.

PMID- 9518727
TI  - Extracellular ATP directly gates a cation-selective channel in rabbit airway
      ciliated epithelial cells.
AB  - 1. A membrane conductance activated by extracellular ATP was identified and
      characterized in freshly dissociated rabbit airway ciliated cells using the whole
      cell and outside-out patch configurations of the patch-clamp technique. 2. In
      solutions designed to maximize currents through voltage-gated calcium channels,
      there were no indications of voltage-gated Ba2+ currents. 3. Extracellular ATP
      (but not UTP or ADP) activated a membrane conductance which remained activated
      for several minutes in the presence of ATP. The conductance was permeable to
      monovalent and divalent cations with approximate relative permeabilities (P) for
      PBa : PCs : PTEA of 4 : 1 : 0.1. Permeability to Cl- was negligible. 4. Including
      GDP-beta-S in the intracellular solution did not inhibit the effects of ATP, nor
      did GTP-gamma-S irreversibly activate the conductance. 5. In outside-out membrane
      patches, with GDP-beta-S in the pipette solution, ATP activated ion channels
      which had a chord conductance of approximately 6 pS in symmetrical 150 mM CsCl
      solutions at -120 mV. 6. Suramin (100 microM) inhibited the whole-cell currents
      activated by ATP (200 microM) by 93 +/- 3 %. Similar effects of suramin were
      observed on ATP-activated channels in outside-out membrane patches. 7.
      Extracellular ATP had a priming action on the response to subsequent exposure to
      ATP. At -40 mV, the time to half-maximal current activation (t1/2) was 46 +/- 9 s
      during the first exposure to 200 microM ATP and decreased to 5 +/- 3 s during a
      second exposure to the same concentration of ATP. The priming action of ATP was
      not inhibited by including GDP-beta-S in the intracellular solution. 8. The
      initial rate of activation increased with the concentration of ATP, and was
      voltage sensitive. During the first exposure to 200 microM ATP, t1/2 at +40 mV
      was 4-fold longer than t1/2 at -40 mV. 9. Half-maximal activation of the
      conductance shifted from 210 +/- 30 to 14 +/- 4 microM added ATP when CaCl2 in
      the extracellular solution was reduced from 1.58 to 0. 01 mM. The Hill
      coefficient for ATP was 1.2 in both solutions.10. These observations suggest that
      a form of ATP uncomplexed with divalent cations directly gates an ion channel
      (P2X receptor) in rabbit airway ciliated cells, which serves as a pathway for
      Ca2+ influx. This purinoceptor may contribute to sustained ciliary activation
      during prolonged exposures to ATP.

PMID- 9518728
TI  - Ca2+-dependent inactivation of large conductance Ca2+-activated K+ (BK) channels
      in rat hippocampal neurones produced by pore block from an associated particle.
AB  - 1. Recordings of the activity of the large conductance Ca2+-activated K+ (BK)
      channel from over 90 % of inside-out patches excised from acutely dissociated
      hippocampal CA1 neurones revealed an inactivation process dependent upon the
      presence of at least 1 microM intracellular Ca2+. Inactivation was characterized
      by a sudden switch from sustained high open probability (Po) long open time
      behaviour to extremely low Po, short open time channel activity. The low Po state
      (mean Po, 0.001) consisted of very short openings (time constant (tau),
      approximately 0.14 ms) and rare longer duration openings (tau, approximately 3.0
      ms). 2. Channel inactivation occurred with a highly variable time course being
      observed either prior to or immediately upon patch excision, or after up to 2 min
      of inside-out recording. Inactivation persisted whilst recording conditions were
      constant. 3. Inactivation was reversed by membrane hyperpolarization, the rate of
      recovery increasing with further hyperpolarization and higher extracellular K+.
      Inactivation was also reversed when the intracellular Ca2+ concentration was
      lowered to 100 nM and was permanently removed by application of trypsin to the
      inner patch surface. In addition, inactivation was perturbed by application of
      either tetraethylammonium ions or the Shaker (Sh)B peptide to the inner membrane
      face. 4. During inactivation, channel Po was greater at hyperpolarized rather
      than depolarized potentials, which was partly the result of a greater number of
      longer duration openings. Depolarizing voltage steps (-40 to +40 mV) applied
      during longer duration openings produced only short duration events at the
      depolarized potential, yielding a transient ensemble average current with a rapid
      decay (tau, approximately 3.8 ms). 5. These data suggest that hippocampal BK
      channels exhibit a Ca2+-dependent inactivation that is proposed to result from
      block of the channel by an associated particle. The findings that inactivation
      was removed by trypsin and prolonged by decreasing extracellular potassium
      suggest that the blocking particle may act at the intracellular side of the
      channel.

PMID- 9518729
TI  - Calcium current activated by potassium ions in voltage-clamped rat hippocampal
      pyramidal neurones.
AB  - 1. Neuronal activity results in local elevation of extracellular K+ concentration
      ([K+]o). 2. Using the patch-clamp technique in the whole-cell configuration, we
      investigated whether extracellular K+ activates non-voltage-operated Ca2+
      channels in pyramidal cells cultured from rat embryonic hippocampi. 3. K+ (12 mM)
      reversibly activated a sustained inward current at a holding potential of -100
      mV. Membrane conductance and variance of noise were significantly increased by
      K+. This current could be observed at membrane potentials negative to +60 mV. 4.
      Inhibitors of inward rectifier K+ channels and hyperpolarization-induced cation
      current reduced the current only at potentials negative to -50 mV. 5. The K+
      induced current was activated in Na+-free but not in Ca2+-free medium, did not
      depend on cytosolic [Cl-], and was blocked by Cd2+ but not by organic channel
      inhibitors. 6. Half-maximal activation of the current (at -100 mV) was attained
      at [K+]o approximately 20 mM. 7. The current is similar to Igl, a K+-induced Ca2+
      current described in glomerulosa cells. It was also present in pyramidal cells
      from prefrontal cortex but not in hippocampal bipolar and glial cells. 8.
      Activation of K+-induced Ca2+ current may elevate cytoplasmic [Ca2+] at [K+]o
      levels which are insufficent to activate voltage-dependent Ca2+ channels.

PMID- 9518730
TI  - Dorsal medullary 5-HT3 receptors and sympathetic premotor neurones in the rat.
AB  - 1. Our aim was to determine whether the cardiovascular neurones in the rostro
      ventrolateral medulla (CV-RVLM neurones) were involved in the sympathoexcitation
      induced by stimulation of 5-HT3 receptors in the region of the nucleus tractus
      solitarii (NTS). Experiments were performed in pentobarbitone-anaesthetized rats,
      artificially ventilated and paralysed with pancuronium bromide. 2. Using
      extracellular recordings, different types of RVLM neurones were characterized:
      cardiovascular (CV), ventilation-related and baroreflex-insensitive
      (unidentified) neurones. The CV-RVLM cells were further subdivided into three
      populations according to their axonal conduction velocities: A (1.2 +/- 0.1 m s
      1), B (2.5 +/- 0.2 m s-1) and C (6.8 +/- 1.1 m s-1). 3. Only the CV-RVLM neurones
      of the A and B categories were partially inhibited (-30 %) by a hypotensive dose
      (2.5 microg kg-1 i.v.) of clonidine. 4. Microinjections into the region of the
      commissural NTS of 1-(m-chlorophenyl)-biguanide (CPBG, 2 nmol), a selective 5-HT3
      receptor agonist, elicited an increase in both lumbar sympathetic nerve discharge
      (SND) and arterial pressure. In addition, this treatment produced a marked
      excitation of CV-RVLM neurones of the A and B categories, without affecting those
      of the C type, as well as ventilation-related and unidentified RVLM cells. 5. The
      activity of the CV neurones in the caudo-ventrolateral part of the medulla
      oblongata (CV-CVLM) was not modified by 5-HT3 receptor stimulation in the NTS. 6.
      Prior intra-NTS microinjections of ondansetron (300 pmol, a selective 5-HT3
      receptor antagonist) into the region of the commissural NTS prevented the
      excitation of A and B CV-RVLM neurones induced by CPBG. 7. Intracarotid
      administration of saline saturated with CO2 (chemoreceptor activation) elicited
      both an increase in the SND and an excitation of the clonidine-insensitive CV
      RVLM neurones of the C type, without affecting A and B neurones. 8. In
      conclusion, the sympathoexcitation elicited following 5-HT3 receptor stimulation
      in the region of the commissural NTS of pentobarbitone-anaesthetized rats seems
      to result from the excitation of two different pools of clonidine-sensitive CV
      RVLM neurones. These neurones are apparently not involved in the sympathetic
      component of the chemoreceptor reflex.

PMID- 9518731
TI  - The ion selectivity of a membrane conductance inactivated by extracellular
      calcium in Xenopus oocytes.
AB  - 1. The ion selectivity of a membrane ion conductance that is inactivated by
      extracellular calcium (Ca2+o) in Xenopus oocytes has been studied using the
      voltage-clamp technique. 2. The reversal potential of the Ca2+o-sensitive current
      (Ic) was measured using voltage ramps (-80 to +40 mV) as a function of the
      external concentration (12-240 mM) of NaCl or KCl. The direction and amplitude of
      the shifts in reversal potentials are consistent with permeability ratios of
      1:0.99:0.24 for K+:Na+:Cl-. 3. Current-voltage (I-V ) relations of Ic, determined
      during either voltage ramps of 0.5 s duration or at steady state, displayed
      pronounced rectification at both hyperpolarized and depolarized potentials.
      However, instantaneous I-V relations showed less rectification and could be
      fitted by the constant field equation assuming the above K+:Na+:Cl- permeability
      ratios. 4. Ion substitution experiments indicated that relatively large organic
      monovalent cations and anions are permeant through Ic channels with the
      permeability ratios K+:NMDG+:TEA+:TPA+:TBA+:Gluc- = 1:0.45:0. 35:0.2:0.2:0.2. 5.
      External amiloride (200 microM), gentamicin (220 microM), flufenamic acid (40
      microM), niflumic acid (100 microM), Gd3+ (0.3 microM) or Ca2+ (200 microM)
      caused reversible block of Ic without changing its reversal potential. 6.
      Preinjection of oocytes with antisense oligonucleotide against connexin 38, the
      Xenopus hemi-gap-junctional protein, inhibited Ic by 80 % without affecting its
      ion selectivity, thus confirming and extending the recent suggestion of Ebihara
      that Ic represents current carried through hemi-gap-junctional channels. 7. In
      vitro and in vivo maturation of oocytes resulted in a significant decrease in Ic
      conductance to 7 % and 2 % of control values, respectively. This developmental
      downregulation of Ic minimizes any toxic effect Ic activation would have when the
      mature egg is released into Ca2+o-free pond water. 8. The results of this study
      are discussed in relation to other Ca2+o-inactivated conductances seen in a wide
      variety of cell types and which have previously been interpreted as arising
      either from Ca2+o-masked channels or from changes in the ion selectivity of
      voltage-gated Ca2+ or K+ channels.

PMID- 9518733
TI  - Streptomycin inhibition of myogenic tone, K+-induced force and block of L-type
      calcium current in rat cerebral arteries.
AB  - 1. Streptomycin has been demonstrated to inhibit mechanosensitive conductances in
      a wide variety of cell types, including muscle. The action of streptomycin on rat
      cerebral arteries that exhibit pressure-induced myogenic response was
      investigated. 2. Pressure-induced tone, measured using isobaric myography, in
      isolated pressurized cerebral arteries was reversibly and concentration
      dependently inhibited by streptomycin with an IC50 of 2.6 mM. 3. Isometric K+
      induced force, measured using isometric myography, is supported by voltage-gated
      Ca2+ entry. Streptomycin reversibly and concentration-dependently inhibited
      isometric force with an IC50 of 1.71 mM. 4. Voltage-gated macroscopic inward Ca2+
      channel currents were recorded from freshly isolated rat basilar myocytes. These
      were reversibly and concentration-dependently inhibited by streptomycin with an
      IC50 of 1.79 and 0.47 mM when 10 and 1.8 mM CaCl2, respectively, was used as the
      charge carrier. 5. These data suggest that streptomycin inhibits myogenic tone
      and K+-induced isometric force largely by blockade of L-type, dihydropyridine
      sensitive Ca2+ channels. In conclusion, streptomycin is not useful in the
      investigation of stretch-activated channels which may underlie the myogenic
      response of rat small cerebral arteries.

PMID- 9518732
TI  - Cytochrome P450: a novel system modulating Ca2+ channels and contraction in
      mammalian heart cells.
AB  - 1. Cytochrome P450 (P450) is a ubiquitous enzyme system that catalyses oxidative
      reactions of numerous endogenous and exogenous compounds. The modulatory effects
      of P450 on the L-type Ca2+ current (ICa), intracellular free Ca2+ signals and
      cell shortening were assessed in adult rat single ventricular myocytes. 2. Bath
      administration of the imidazole antimycotics, clotrimazole, econazole and
      miconazole, which are potent P450 inhibitors, significantly suppressed cardiac
      ICa. While the Ca2+ channel antagonist nifedipine blocked ICa within 30 s,
      clotrimazole-induced suppression of ICa required 5.1 +/- 0.4 min (n = 14) to
      reach a steady low level. The suppression of ICa was dose dependent and recovered
      after washout of clotrimazole. Intracellular dialysis with the P450 antibody anti
      rat CYP1A2 also significantly reduced cardiac ICa. 3. Additional administration
      of the beta-adrenergic agonist isoprenaline (1 microM) or the membrane-permeable
      8-bromo-cAMP (2 mM) completely reversed the suppressant effects of clotrimazole
      and NaCN on ICa. In addition, intracellular dialysis with 2 mM cAMP abolished the
      P450 inhibitor-induced suppression of ICa. Phosphorylation of the channel with
      hydrolysis-resistant ATPgammaS prevented the suppressant effect of clotrimazole
      on ICa. Furthermore, dephosphorylation of the Ca2+ channel with intracellular
      dialysis with phosphatase types I and II reduced ICa by 85 +/- 3 % and abolished
      clotrimazole-induced suppression of ICa. 4. Extracellular administration of the
      phospholipase A2 inhibitors mepacrine and 4-bromophenacyl bromide significantly
      suppressed ICa. 5. Clotrimazole, econazole, miconazole and CN- also significantly
      inhibited intracellular free Ca2+ signals and cell shortening in rat single
      ventricular myocytes. 6. Intracellular cAMP content was significantly reduced in
      isolated ventricular myocytes incubated with clotrimazole or CN-. Extracellular
      administration of 11, 12-epoxyeicosatrienoic acid, one of the P450-mediated
      metabolites of arachidonic acid, enhanced ICa and intracellular cAMP content. The
      epoxyeicosatrienoic acid also restored the amplitude of the reduced ICa in P450
      antibody-dialysed myocytes. 7. The present data suggest that cytochrome P450
      modulates cardiac ICa and cell contraction, and the modulation may result from
      changes in intracellular levels of cAMP by P450- mediated metabolites of
      arachidonic acid.

PMID- 9518734
TI  - Fundamental calcium release events revealed by two-photon excitation photolysis
      of caged calcium in Guinea-pig cardiac myocytes.
AB  - 1. In cardiac muscle, 'Ca2+ sparks' have been proposed to underlie Ca2+-induced
      Ca2+ release (CICR), and to result from openings of clusters of Ca2+ channels
      (ryanodine receptors; RyRs) located in the sarcoplasmic reticulum membrane. 2. To
      investigate the elementary nature of these Ca2+ signals directly, a diffraction
      limited point source of Ca2+ was created in single cardiac myocytes by two-photon
      excitation photolysis of caged Ca2+. Simultaneously, concentration profiles of
      released Ca2+ were imaged at high temporal and spatial resolution with a laser
      scanning confocal microscope. 3. This approach enabled us to generate and detect
      photolytic Ca2+ signals that closely resembled the Ca2+ sparks occurring
      naturally, not only in amplitude and size, but also in their ability to trigger
      additional Ca2+ sparks or Ca2+ waves. 4. Surprisingly, at low photolytic power
      minuscule events with estimated Ca2+ release fluxes 20-40 times smaller than
      those calculated for a typical Ca2+ spark were directly resolved. These events
      appeared to arise from the opening of a more limited number of RyRs (possibly
      one) or from RyRs exhibiting a different gating mode and may correspond to the
      elusive 'Ca2+ quark'. 5. The Ca2+ quark represents the fundamental Ca2+ release
      event of excitable cells implementing hierarchical Ca2+ signalling systems with
      Ca2+ release events of various but distinct amplitude levels (i.e. Ca2+ quarks,
      Ca2+ sparks and full cellular Ca2+ transients). 6. A graded recruitment of
      nanoscopic Ca2+ release domains (i.e. Ca2+ quarks) exhibiting variable degrees of
      spatial coherence and coupling may then build up intermediate Ca2+ signalling
      events (i.e. Ca2+ sparks). This mechanism suggests the existence of Ca2+ sparks
      caused by gating of a variable fraction of RyRs from within an individual
      cluster. Additional mobilization of a variable number of these Ca2+ sparks
      enables cardiac cells to show graded cellular Ca2+ transients. Similar
      recruitment processes may underlie regulation of Ca2+ signalling on the cellular
      level in general.

PMID- 9518735
TI  - Repolarizing K+ currents in rabbit heart Purkinje cells.
AB  - 1. Electrophysiological experiments on single myocytes obtained from Purkinje
      fibres and ventricular tissue of adult rabbit hearts were done to compare the
      contributions of three potassium (K+) currents to the action potentials in these
      two tissues. 2. In Purkinje cells reductions in extracellular potassium, [K+]o,
      from normal (5.4 mM) to 2.0 mM resulted in a large hyperpolarization and marked
      lengthening of the action potential. In ventricular myocytes, these changes were
      much less pronounced. Voltage clamp measurements demonstrated that these
      differences were mainly due to a much smaller inward rectifier K+ current, IK1,
      in Purkinje cells than in ventricular myocytes. 3. Application of 4-aminopyridine
      (4-AP, 2 mM) showed that all Purkinje cells exhibited a very substantial Ca2+
      independent transient K+ outward current, It. 4-AP significantly broadened the
      early, rapid repolarization phase of the action potential. 4. Selective
      inhibitors of the fast component, IK, r (MK-499, 200 nM) and the slow component
      IK,s (L-735821 (propenamide), 20 nM) of the delayed rectifier K+ currents both
      significantly lengthened the action potential, suggesting that these conductances
      are present, but very small (< 20 pA) in Purkinje cells. Attempts to identify
      time- and voltage-dependent delayed rectifier K+ current(s) in Purkinje cells
      failed, although a slow delayed rectifier was observed in ventricular myocytes.
      5. These results demonstrate significant differences in action potential
      waveform, and underlying K+ currents in rabbit Purkinje and ventricular myocytes.
      Purkinje cells express a much smaller IK1, and a larger It than ventricular
      myocytes. These differences in current densities can explain some of the most
      important electrophysiological properties of these two tissues.

PMID- 9518736
TI  - Cl- transport by cystic fibrosis transmembrane conductance regulator (CFTR)
      contributes to the inhibition of epithelial Na+ channels (ENaCs) in Xenopus
      oocytes co-expressing CFTR and ENaC.
AB  - 1. Epithelial Na+ channels (ENaCs) are inhibited by the cystic fibrosis
      transmembrane conductance regulator (CFTR) when CFTR is activated by protein
      kinase A. Since cAMP-dependent activation of CFTR Cl- conductance is defective in
      cystic fibrosis (CF), ENaC currents are not inhibited by CFTR. This could explain
      the enhanced Na+ conductance found in CF. In the present study, we examined
      possible mechanisms of interaction between CFTR and ENaC co-expressed in Xenopus
      oocytes. 2. The magnitude of CFTR Cl- currents activated by 3-isobutyl-1
      methylxanthine (IBMX) in oocytes co-expressing either wild-type or mutant CFTR
      and ENaC determined the degree of downregulation of ENaC currents. 3. The ability
      of CFTR to inhibit ENaC currents was significantly reduced either when
      extracellular Cl- was replaced by poorly conductive anions, e.g. SCN- or
      gluconate, or when CFTR was inhibited by diphenylamine-carboxylate (DPC, 1 mmol l
      1). 4. Downregulation of ENaC was more pronounced at positive when compared with
      negative clamp voltages. This suggests that outward currents, i.e. influx of Cl-
      through activated CFTR most effectively downregulated ENaC. 5. Activation of
      endogenous Ca2+-activated Cl- currents by 1 micromol l-1 ionomycin did not
      inhibit ENaC current. This suggests that inhibition of ENaC mediated by Cl-
      currents may be specific to CFTR. 6. The present findings indicate that
      downregulation of ENaC by CFTR is correlated to the ability of CFTR to conduct Cl
      . The data have implications for how epithelia switch from NaCl absorption to
      NaCl secretion when CFTR is activated by secretagogues.

PMID- 9518737
TI  - Transport mechanisms for iron and other transition metals in rat and rabbit
      erythroid cells.
AB  - 1. Earlier studies have shown that Fe2+ transport into erythroid cells is
      inhibited by several transition metals (Mn2+, Zn2+, Co2+, Ni2+) and that Fe2+
      transport can occur by two saturable mechanisms, one of high affinity and the
      other of low affinity. Also, the transport of Zn2+ and Cd2+ into erythroid cells
      is stimulated by NaHCO3 and NaSCN. The aim of the present investigation was to
      determine whether all of these transition metals can be transported by the
      processes described for Fe2+, Zn2+ and Cd2+ and to determine the properties of
      the transport processes. 2. Rabbit reticulocytes and mature erythrocytes and
      reticulocytes from homozygous and heterozygous Belgrade rats were incubated with
      radiolabelled samples of the metals under conditions known to be optimal for high
      and low-affinity Fe2+ transport and for the processes mediated by NaHCO3 and
      NaSCN. 3. All of the metals were transported by the high- and low-affinity Fe2+
      transport processes and could compete with each other for transport. The Km and
      Vmax values and the effects of incubation temperature and metabolic inhibitors
      were similar for all the metals. NaHCO3 and NaSCN increased the uptake of Zn2+
      and Cd2+ but not the other metals. 4. The uptake of all of the metals by the high
      affinity process was much lower in reticulocytes from homozygous Belgrade rats
      than in those from heterozygous animals, but there was no difference with respect
      to low-affinity transport. 5. It is concluded that the high- and low-affinity
      'iron' transport mechanisms can also transport several other transition metals
      and should therefore be considered as general transition metal carriers.

PMID- 9518738
TI  - The role of GABAergic inputs for coincidence detection in the neurones of nucleus
      laminaris of the chick.
AB  - 1. Synaptic inputs to nucleus laminaris (NL) neurones were studied in a brainstem
      slice preparation of chick embryos (E15-20) using the whole-cell patch clamp
      technique. NL neurones are third order auditory neurones and are proposed to
      behave as coincidence detectors concerned with interaural timing discrimination.
      2. Under voltage clamp conditions, electrical stimuli applied to either ventral
      or dorsal dendritic layers evoked EPSCs. These fast currents decayed with a time
      constant of 1.1 ms near the resting potential, reversed close to 0 mV, and were
      blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 20 microM) or 6, 7-dinitro
      quinoxaline-2,3-dione (DNQX, 20 microM). Coincident or near coincident
      stimulation of the ventral and the dorsal dendritic layers increased the
      probability of action potential generation (response probability). 3. In the
      presence of CNQX (40 microM) other postsynaptic currents (PSCs) were observed,
      which reversed close to the equilibrium potential for chloride (ECl), and were
      reversibly blocked by bicuculline (20 microM) and, therefore, were mediated by
      GABAA receptors. Spontaneous GABAergic PSCs were inward going near the resting
      membrane potential immediately after starting whole-cell recording with a low Cl-
      (5 mM, ECl = -90 mV) pipette medium, but became outward-going with time. This
      indicates that GABAergic inputs may generate depolarizing potentials in intact NL
      neurones. 4. Local GABA (10 microM) application reduced both the EPSP and EPSC
      amplitude and shortened the EPSP decay time constant (from 5.3 to 2. 1 ms), while
      the EPSC decay time constant was not affected (from 1.3 to 1.2 ms). These GABA
      effects were mostly due to the shunting conductance of the postsynaptic GABAA
      receptors. 5. Depolarizing current injections combined with electrical stimuli to
      a unilateral axon bundle simulated bilateral synaptic inputs. Response
      probability increased with decreased interstimulus intervals, while local GABA
      (10 microM) application to the soma narrowed the time dependence of the response
      probability. 6. These results suggest that GABAergic inputs to NL neurones may
      serve to improve coincidence detection of the bilateral excitatory inputs through
      an increase in membrane conductance.

PMID- 9518739
TI  - Possible involvement of the novel CPI-17 protein in protein kinase C signal
      transduction of rabbit arterial smooth muscle.
AB  - 1. CPI-17 has recently been identified as a novel protein in vascular smooth
      muscle. In vitro , its phosphorylation and thiophosphorylation by protein kinase
      C (PKC) specifically inhibits the type 1 class of protein phosphatases, including
      myosin light chain (MLC) phosphatase. 2. Both of the phosphorylated CPI-17 states
      dose-dependently potentiated submaximal contractions at constant [Ca2+] in beta
      escin-permeabilized and Triton X-100-demembranated arterial smooth muscle, but
      produced no effect in intact and less intensely permeabilized (alpha-toxin)
      tissue. Thiophosphorylated CPI-17 (tp-CPI) induced large contractions even under
      Ca2+-free conditions and decreased Ca2+ EC50 by more than an order of magnitude.
      Unphosphorylated CPI-17 produced minimal but significant effects. 3. tp-CPI
      substantially increased the steady-state MLC phosphorylation to Ca2+ ratios in
      beta-escin preparations. 4. tp-CPI affected the kinetics of contraction and
      relaxation and of MLC phosphorylation and dephosphorylation in such a manner that
      indicates its major physiological effect is to inhibit MLC phosphatase. 5.
      Results from use of specific inhibitors in concurrence with tp-CPI repudiate the
      involvement of general G proteins, rho A or PKC itself in the Ca2+ sensitization
      by tp-CPI. 6. Our results indicate that phosphorylation of CPI-17 by PKC
      stimulates binding of CPI-17 to and subsequent inhibition of MLC phosphatase.
      This implies that CPI-17 accounts largely for the heretofore unknown signalling
      pathway between PKC and inhibited MLC phosphatase.

PMID- 9518741
TI  - Coupling of sympathetic and somatic motor outflows from the spinal cord in a
      perfused preparation of adult mouse in vitro.
AB  - 1. The relationship between sympathetic and somatic motor outflows from thoraco
      lumbar spinal cord was investigated in a novel arterially perfused trunk
      hindquarters preparation of adult mouse. 2. Ongoing activity was present in both
      somatic motor (obturator, sciatic or femoral nerves) and sympathetic outflows
      (either renal nerve or abdominal sympathetic chain). Sympathetic activity was
      rhythmic with bursts frequencies of 0.6-2.2 Hz. No obvious rhythmic activity was
      found in the somatic motor outflow. There were periods during which sympathetic
      and somatic motor activity were correlated. 3. Addition of NMDA (20-80 microM) to
      the perfusate elicited repetitive burst discharges in the somatic motor outflow
      which were sometimes rhythmic. The frequency of these burst discharges/rhythmic
      activity varied between preparations but in all cases increased with increasing
      NMDA concentration. 4. NMDA induced burst discharges in the sympathetic outflow.
      This bursting activity was of the same frequency as the somatic motor outflow and
      the two were coupled as revealed by correlation analysis. Periods of coupling
      persisted for up to 3 min. 5. Administration of hexamethonium (300 microM), to
      block sympathetic ganglionic transmission, had no effect on the somatic motor
      activity but severely attenuated sympathetic nerve discharge. 6. The thoraco
      sacral cord therefore has the neuronal machinery necessary for generating and
      coupling activity in somatic motor and sympathetic outflows. Our findings
      indicate a dynamic control over the degree of coupling. We discuss that the
      synchronization of these neural outflows reflects either coupling between two
      independent mechanisms or the presence of a common synaptic driver impinging on
      both somatic motor and sympathetic neurones.

PMID- 9518740
TI  - Endogenous pacemaker activity of rat tumour somatotrophs.
AB  - 1. Cells derived from a rat pituitary tumour (GC cell line) that continuously
      release growth hormone behave as endogenous pacemakers. In simultaneous patch
      clamp recordings and cytosolic Ca2+ concentration ([Ca2+]i) imaging, they
      displayed rhythmic action potentials (44.7 +/- 2.7 mV, 178 +/- 40 ms, 0.30 +/-
      0.04 Hz) and concomitant [Ca2+]i transients (374 +/- 57 nM, 1.0 +/- 0.2 s, 0.27
      +/- 0.03 Hz). 2. Action potentials and [Ca2+]i transients were reversibly blocked
      by removal of external Ca2+, addition of nifedipine (1 microM) or Ni2+ (40
      microM), but were insensitive to TTX (1 microM). An L-type Ca2+ current activated
      at -33.6 +/- 0.4 mV (holding potential (Vh), -40 mV), peaked at -1.8 +/- 1.3 mV,
      was reduced by nifedipine and enhanced by S-(+)-SDZ 202 791. A T/R-type Ca2+
      current activated at -41.7 +/- 2.7 mV (Vh, -80 or -60 mV), peaked at -9.2 +/- 3.0
      mV, was reduced by low concentrations of Ni2+ (40 microM) or Cd2+ (10 microM) and
      was toxin resistant. Parallel experiments revealed the expression of the class E
      calcium channel alpha1-subunit mRNA. 3. The K+ channel blockers TEA (25 mM) and
      charybdotoxin (10-100 nM) enhanced spike amplitude and/or duration. Apamin (100
      nM) also strongly reduced the after-spike hyperpolarization. The outward K+ tail
      current evoked by a depolarizing step that mimicked an action potential reversed
      at -69. 8 +/- 0.3 mV, presented two components, lasted 2-3 s and was totally
      blocked by Cd2+ (400 microM). 4. The slow pacemaker depolarization (3.5 +/- 0.4
      s) that separated consecutive spikes corresponded to a 2- to 3-fold increase in
      membrane resistance, was strongly Na+ sensitive but TTX insensitive. 5. Computer
      simulations showed that pacemaker activity can be reproduced by a minimum of six
      currents: an L-type Ca2+ current underlies the rising phase of action potentials
      that are repolarized by a delayed rectifier and Ca2+-activated K+ currents. In
      between spikes, the decay of Ca2+-activated K+ currents and a persistent inward
      cationic current depolarize the membrane, activate the T/R-type Ca2+ current and
      initiate a new cycle.

PMID- 9518742
TI  - The canine phrenic-to-intercostal reflex.
AB  - 1. Paralysis of the diaphragm in the dog causes a non-vagal, non-chemical
      increase in the activity of the inspiratory intercostal muscles. In the present
      studies, the hypothesis was tested that phrenic afferent fibres may elicit a
      reflex inhibition of inspiratory intercostal activity. 2. The electrical activity
      of the three groups of inspiratory intercostal muscles (parasternal intercostals,
      external intercostals, levator costae) was recorded in twenty vagotomized,
      spontaneously breathing dogs, and the proximal end of one or both C5 phrenic
      nerve roots was stimulated during inspiration. 3. Stimulation of the ipsilateral
      and contralateral C5 phrenic roots caused an immediate reduction in inspiratory
      intercostal activity. This reduction was abolished when phrenic stimulation was
      repeated after section of the C5 dorsal roots. 4. The reduction in external
      intercostal and levator costae activity during bilateral C5 afferent stimulation
      appeared when the stimulus strength was 3 times the motor threshold and it
      increased in magnitude when stimulus intensity was increased further. In
      contrast, the reduction in parasternal intercostal activity occurred only when
      the stimulus strength was 12 times the motor threshold. 5. These observations
      confirm the hypothesis that diaphragmatic receptors may reflexly inhibit efferent
      activity to the inspiratory intercostal muscles, in particular the external
      intercostals and levator costae. This inhibition appears to be primarily mediated
      by small myelinated fibres.

PMID- 9518743
TI  - Osmotic hypertonicity of the renal medulla during changes in renal perfusion
      pressure in the rat.
AB  - 1. The relationship between renal perfusion pressure (RPP) and ion concentration
      in renal medulla was studied in anaesthetized rats. RPP was changed in steps
      within the pressure range 130-80 mmHg, while tissue electrical admittance (Y,
      index of interstitial ion concentration) and medullary and cortical blood flow
      (MBF and CBF; laser Doppler flowmetry) were measured, along with glomerular
      filtration rate (C in) and renal excretion. 2. With a RPP reduction from 130 to
      120 mmHg, tissue Y remained stable; at 100 and 80 mmHg, Y was 5 and 17 % lower,
      respectively, than at 120 mmHg. 3. CBF fell less than RPP (partial
      autoregulation) in the range 130-100 mmHg only. MBF was autoregulated within 120
      100 mmHg, but not above or below this range. 4. Each step of RPP reduction was
      followed by a decrease in sodium and water excretion (UNaV and V). The osmolality
      of excised inner medulla fragments was similar at 120 and 105 mmHg (586 +/- 45
      and 618 +/- 35 mosmol (kg H2O)-1, respectively) but lower at 80 mmHg (434 +/- 31
      mosmol (kg H2O)-1, P < 0.01); the ion concentration changed in parallel. 5. The
      data show that medullary hypertonicity was well preserved during RPP fluctuations
      within 130-100 mmHg, but not below this range. RPP-dependent changes of UNaV and
      V were not clearly associated with changes in solute concentration in medullary
      tissue.

PMID- 9518744
TI  - Developmental regulation of glucogenesis in the sheep fetus during late
      gestation.
AB  - 1. Using tracer methodology, endogenous glucose production was measured in twenty
      six chronically catheterized sheep fetuses during normal fed conditions and in
      response to a 48 h period of maternal fasting at different gestational ages
      during the last 10-15 days of gestation (term, 145 +/- 2 days). 2. In normal fed
      conditions, the rate of fetal glucose production was negligible until 143-145
      days when it rose significantly to account for 50 % of the glucose used by the
      fetus. The rise in fetal glucogenesis towards term closely parallelled the normal
      prepartum rise in fetal plasma cortisol and catecholamines. 3. Maternal fasting
      for 48 h induced endogenous glucose production in fetuses at 139-141 days but not
      at 133-135 days of gestation. Maternal fasting also induced increases in the
      plasma cortisol and noradrenaline levels in all the fetuses studied. Fetal plasma
      cortisol levels at the end of the fast and the increment in fetal plasma cortisol
      during maternal fasting were significantly greater in the older groups of fasted
      animals. 4. When the data from all the fetuses were combined, partial correlation
      analysis of fetal glucose production and the log plasma concentrations of
      cortisol and total catecholamines showed that plasma cortisol was the predominant
      regulator of fetal glucogenesis during late gestation. However, once plasma
      cortisol levels exceeded 17.5 ng ml-1, plasma catecholamines were a major
      influence on fetal glucogenesis. 5. The results show that glucogenesis occurs in
      fetal sheep during late gestation in conditions in which the fetal plasma
      concentrations of cortisol and catecholamines are elevated. They also suggest
      that cortisol enhances the capacity for glucogenesis in utero, while
      catecholamines actually activate glucose production in sheep fetuses close to
      term.

PMID- 9518745
TI  - Evidence that interleukin-6 is produced in human skeletal muscle during prolonged
      running.
AB  - 1. This study was performed to test the hypothesis that inflammatory cytokines
      are produced in skeletal muscle in response to prolonged intense exercise. Muscle
      biopsies and blood samples were collected from runners before, immediately after,
      and 2 h after a marathon race. 2. The concentration of interleukin (IL)-6 protein
      in plasma increased from 1.5 +/- 0.7 to 94.4 +/- 12.6 pg ml-1 immediately post
      exercise and to 22.1 +/- 3.8 pg ml-1 2 h post-exercise. IL-1 receptor antagonist
      (IL-1ra) protein in plasma increased from 123 +/- 23 to 2795 +/- 551 pg ml-1, and
      increased further to 4119 +/- 527 pg ml-1 2 h post-exercise. 3. The comparative
      polymerase chain reaction technique was used to evaluate mRNA for IL-6, IL-1ra,
      IL-1beta and tumour necrosis factor (TNF)-alpha in skeletal muscle and blood
      mononuclear cells (BMNC) (n = 8). Before exercise, mRNA for IL-6 could not be
      detected either in muscle or in BMNC, and was only detectable in muscle biopsies
      (5 out of 8) after exercise. Increased amounts of mRNA for IL-1ra were found in
      two muscle biopsies and five BMNC samples, and increased amounts of IL-1beta mRNA
      were found in one muscle and four BMNC samples after exercise. TNF-alpha mRNA was
      not detected in any samples. 4. This study suggests that exercise-induced
      destruction of muscle fibres in skeletal muscles may trigger local production of
      IL-6, which stimulates the production of IL-1ra from circulating BMNC.

PMID- 9518747
TI  - Utilization of advanced hygienist skills in the private practice.
AB  - PURPOSE: The purpose of this study was to survey dental hygiene graduates to
      determine utilization in the private practice setting of expanded functions
      taught in school. METHOD: A questionnaire was sent to 90 dental hygiene graduates
      from the classes of 1990-1994, of Indiana University-Purdue University, Fort
      Wayne. Analysis was done on utilization of specific expanded functions taught in
      school. Frequency tabulations of procedures performed and adequacy of preparation
      were done using the SAS software. The results were graphically represented in
      tables. RESULTS: Equal response from each class resulted in the total response
      rate of 74%. The expanded functions most frequently performed by dental
      hygienists were placing sealants followed by making cast impressions. Placing
      temporary and amalgam restorations were rarely performed. The majority of
      graduates felt adequately trained to perform these skills. CONCLUSION: Skills
      being required and taught in school are not being delegated in private practice.
      This survey shows the need for curriculum revisions and discrepancies between
      educational requirements and utilization.

PMID- 9518746
TI  - The oral health of Indiana's independent, disabled adults.
AB  - This epidemiological study was conducted to measure the oral health and related
      variables of one of Indiana's special population groups: adults who are
      developmentally disabled, work in sheltered workshops and do not live in staffed
      residential facilities. Fifteen sheltered workshops in ten Indiana counties
      cooperated with this study in which 393 individuals were interviewed and received
      oral screening. Information was gathered regarding oral health status, history of
      utilization of dental services, availability of dental insurance or Medicaid and
      use of tobacco products. This study was conducted by the Indiana Foundation of
      Dentistry for the Handicapped and was funded by the Indiana State Department of
      Health.

PMID- 9518749
TI  - Effectiveness of the dental instrument cassette in the practice setting.

PMID- 9518750
TI  - Valuation brings all parts of dental practice into focus.

PMID- 9518748
TI  - Direct temporary-provisional crown fabrication mends tooth in timely manner.

PMID- 9518751
TI  - Successation or cessation: planning your practice transition.

PMID- 9518752
TI  - Managed dental care: it is here to stay.

PMID- 9518753
TI  - Kaiser Permanente Dental Care Program: focused on managing care, not managed
      care.

PMID- 9518754
TI  - Managed care: a poor prescription for an ailing practice.

PMID- 9518755
TI  - Why me?

PMID- 9518756
TI  - Dental claims review: risk management in a fee-for-service environment.

PMID- 9518757
TI  - Managed care: oral health care for the future. American Dental Hygienists'
      Association.

PMID- 9518758
TI  - A journey from capitation to loss.

PMID- 9518759
TI  - Why I abandoned capitation--empty chair is not a reason to participate.

PMID- 9518760
TI  - United Concordia's rapid growth includes administration of the Tricare--Active
      Duty Family Member Dental Plan.

PMID- 9518761
TI  - Dentistry in the age of DNA.

PMID- 9518762
TI  - Dental practice efficiency & the role of the dental team.

PMID- 9518763
TI  - Kentucky dental practice survey.

PMID- 9518764
TI  - Hepatitis B vaccination: time for a booster?

PMID- 9518765
TI  - Periodontal Screening & Recording.

PMID- 9518766
TI  - Cosmetic oral and maxillofacial surgery.

PMID- 9518767
TI  - Haven't we 'eased' floss into our oral hygiene instruction long enough?
AB  - We have tried to 'ease' the procedure of dental flossing into the job of cleaning
      the teeth long enough. Almost all our clients know about the benefits of flossing
      and that they are supposed to floss. What we have not been successful in teaching
      is that it is not an option; it is an integral part of complete plaque removal.
      Developing and utilizing new methods of instruction to increase the overall
      effectiveness of our dental hygiene education, with the objective of decreasing
      the occurrence of periodontal disease, is then, our challenge.

PMID- 9518768
TI  - Quality assessment in continuing education: an example of an instrument
      sharpening workshop for dental hygienists.

PMID- 9518769
TI  - Meeting the needs of under-serviced communities: one university's externship
      experiment.
AB  - Increasingly, the ability to respond to society's needs is becoming a guiding
      principle for educational institutions. This concept will, in difficult financial
      times, take on even greater significance when all programs will have to justify
      their survival by preparing graduates that can work in areas where there is a
      demonstrable need. The implications of this approach are far-reaching and require
      years of planning to adjust the current focus of a program to meet the new goals.
      In this article, a dental program that set out to broaden the scope of its
      curriculum in order to respond to societal needs will be reviewed.

PMID- 9518770
TI  - The problem-oriented dental record: a key to dental hygiene treatment planning
      and the problem-solving model for dental hygiene practice.
AB  - The problem-solving model for dental hygiene practice requires careful
      assessment, planning, implementation and evaluation to provide quality dental
      hygiene care. To facilitate this problem-solving approach, a method of recording
      information in an organized and highly communicative manner must be established.
      This paper describes the components of a problem-oriented dental record used by
      students at the Vancouver Community College and discusses the benefits of using
      this tool in clinical practice.

PMID- 9518771
TI  - A literature review: oral irrigation therapy. The adjunctive roles for home and
      professional use.
AB  - It is now recognized that there are several different types of periodontal
      infections. As we learn more about the cause of these diseases, it becomes
      obvious that we have treatment options. A successful choice of procedures for
      each individual depends on an accurate diagnosis based on comprehensive data
      collection of clinical and microbiological findings. Treatment choices include a
      non-surgical phase which consists of plaque removal, plaque control, scaling,
      root planing, and the use of chemical agents. For complete debridement of deep
      pockets, furcations or areas with root surface irregularities, surgical access
      may be necessary. When considering drug therapy, it must be noted that systemic
      antibiotics may be necessary to suppress those subgingival periodontal pathogens
      which have the ability to invade the tissue and resist other methods of
      eradication. Removal or alteration of pathogenic flora is mandatory to improve a
      patient's periodontal health. The extensive use of supragingival irrigation as an
      adjunct for treating gingivitis has led to the interest in subgingival irrigation
      as a possible adjunct for treatment of periodontal diseases. Targeted lavage and
      subgingival delivery of effective antimicrobial agents show potential as
      supplemental office procedures or as a component of a home oral hygiene regime.
      Additional research is needed to develop more efficacious chemotherapeutic
      substances than are currently available and to further define the optimum
      application of each. Substantive medicaments that react specifically against
      periodontopathic organisms are essential. Exact frequency and duration of
      professionally-applied and self-administered subgingival irrigation need to be
      determined for maximum results. Further investigation is required to establish
      the potential role of adjunctive irrigation and antimicrobial therapy in the
      treatment of periodontitis. Yet, another important application of irrigation has
      been recognized. Recently, the American Heart Association revised its guidelines
      for the prevention of bacterial endocarditis. The amendments to the dentistry
      sections have been approved by the Council on Dental Therapeutics of the American
      Dental Association. Included in this text is the recommendation that as an
      adjunct to antibiotic prophylaxis, sulcular irrigation with chlorhexidine may be
      useful for those patients considered high risk and/or have poor oral hygiene.
      Irrigation therapy is undergoing extensive scrutiny in the scientific research
      community. Presently, considerable conclusive evidence exists to suggest that
      adjunctive irrigation may play an important role in controlling gingivitis and
      periodontitis. The overwhelming challenge for any and all successful periodontal
      therapy will always remain dependent on patient compliance to regular
      professional and home care.

PMID- 9518773
TI  - A new dental health initiative in British Columbia.

PMID- 9518772
TI  - The impact of demographic, economic and social trends on oral health care.
AB  - Concurrent with the new technologies in oral disease prevention, diagnosis, and
      treatment are the changing global perspectives on health which impact
      significantly on who will actually receive the new technologies and services.
      Issues of access to care, the rapidly changing social, political, and economic
      environments and the growing recognition of the disparities and barriers to oral
      health are stimulating new strategies for positive change and enhancement.
      Governments, in partnership with professional associations, private sector
      concerns and consumer interests in Canada and the United States, have recently
      reviewed current oral health status and identified needs and inequities. A few
      bold new multisectoral initiatives have evolved but not enough to address all the
      trends. The challenges not adequately addressed by current policies and practices
      have been identified. Goals for oral health have been established both nationally
      and internationally to address the trends and the challenges. Critical areas for
      taking action have been also been identified and include research in
      epidemiology, behavioural and social sciences, health services, and evaluation.
      This type of research considers the social and environmental context of where and
      how oral services are provided. Ultimately this is the kind of research that can
      radically change the role of the dental hygienist in the delivery of oral health
      care.

PMID- 9518774
TI  - The efficacy of electric-powered toothbrushes: a literature review.

PMID- 9518775
TI  - Surgical intervention for hyperplastic gingival tissue.

PMID- 9518776
TI  - The dental hygienist's role in screening for oral cancer.

PMID- 9518777
TI  - Guided bone regeneration.

PMID- 9518778
TI  - The collaborative development of: Going to the Dentist: a kit for integrating
      dental information and language skill.

PMID- 9518779
TI  - Immediate dental implants.

PMID- 9518780
TI  - Is dental hygiene a profession? A literature review.
AB  - From a literature review of theories of professionalism, the historical
      development of the attributes of a profession are discussed. This paper then
      discusses various theories of professionalism and specifically examines the
      extent to which the criteria developed by Greenwood are fulfilled by dental
      hygiene. Greenwood's model, which discusses certain attributes that a profession
      should possess, is selected to provide a broader model to analyze the current
      professional status of dental hygiene. Greenwood's model states that a profession
      has acquired: 1) systemic theory, 2) authority, 3) community sanction, 4) ethical
      codes, and 5) a culture. The author will conclude by suggesting possible steps
      the dental hygiene profession could continue to take to acquire these attributes
      and thereby recognition as a profession by other professions, governments and the
      public.

PMID- 9518781
TI  - Use of tetracycline fibre to treat localized unstable periodontitis.
AB  - Tetracycline fibre cords will be introduced in Canada in January 1996. Presently
      it is used in the United States and the placement of the fibres is included
      within the dental hygienists's scope of practice in many states. Dental
      Hygienists in each province may want to request that this procedure be added to
      the list of duties they may perform within their scope of practice. (Although
      tetracycline cords are not yet available in Canada, some offices have been
      permitted to use these products on a trial basis. Presuming they will soon be
      available in Canada, the author suggests they would be a valuable adjunct in
      periodontal therapy.

PMID- 9518782
TI  - What do people want from dentistry? An action research approach.
AB  - Issues surrounding access to dentistry will be presented from information
      gathered during an action research project targeting three population groups.
      This project was conducted by students in the Dental Hygiene Degree Completion
      Program at the University of British Columbia and by the dental hygiene diploma
      students at Camosun College. In contrast to typical empirical dental studies
      which are validated by statistical presentation, action research uses an
      interview process and qualitative analysis to identify what people really think,
      believe and do. College students, independent-living seniors, and low-income
      families were interviewed to determine how they accessed dental care, how they
      liked their dental visits, and how they preferred to receive dental health
      information. Cost, convenience and fear of pain were significant factors which
      influenced whether people attended the dental office. Caring dental health
      providers, comfort and pleasant physical surroundings were important features of
      a dental office visit. Dental health practices, such as brushing and flossing,
      were predominantly learned from the dental profession at the dental office,
      through school programs, or from parents at home. This data challenged our
      previous assumptions about these groups. As the goal of this type of research is
      "action", the information gathered will lead to action plans at the community and
      professional level.

PMID- 9518783
TI  - Dentin hypersensitivity.

PMID- 9518784
TI  - Factors determining the outcome of scaling and root planing.
AB  - Scaling and root planing are the predominant and recognized forms of periodontal
      therapy. They have been known for centuries, and have been investigated with
      increasing intensity since the turn of the century. Scaling and root planing aim
      at therapeutic changes of the "hard tissue lesion" at the root surface, in order
      to render it biologically acceptable to cells capable of attaching to it. Two
      major components of these root surface alterations are calculus and cementum
      alterations. Numerous studies have shown that scaling and root planing
      effectively removes subgingival deposits, and that this removal is seldom
      complete in deeper pockets. Even though beneficial clinical effects of scaling
      and root planing have been shown, it is unlikely that the full potential of
      healing is utilized today due to technical shortcomings. Several studies have
      shown that the design and dimensions of curets as used today are not optimal.
      These instruments are for many situations too big, subject to rapid dulling, and
      produce a smear layer. Chemical agents have been used to remove this layer with
      limited success. The therapist is a virtually unknown factor in the system of
      delivering scaling and root planing. A recent study showed that scaling and root
      planing forces used by different therapists on similar root surfaces varied by
      factors greater than 10. In addition, higher forces were shown to remove
      significantly more root substance. Apparently there is a large subjective
      component included in the delivery of scaling and root planing therapy. Even
      though scaling and root planing have been shown to be effective therapeutic
      procedures, many aspects require more research.

PMID- 9518785
TI  - Dental management of the patient with ESRD.

PMID- 9518786
TI  - Notes on the supply and demand for dental hygienists.

PMID- 9518787
TI  - Back to the future: appropriating our traditions.

PMID- 9518788
TI  - Self-regulation in Alberta, Canada: the achievement of a goal.

PMID- 9518789
TI  - Collaboration of health care professionals: the dental hygienists' role.
AB  - Dental hygienists are primary health care professionals concerned with oral
      health and general well-being of the public. This paper discusses collaboration
      amongst the health professions to further the wellness of Canadians.

PMID- 9518790
TI  - Osseointegrated implants. A part of our future here and now.

PMID- 9518791
TI  - Key elements of the Ontario Regulated Health Professions Act.

PMID- 9518792
TI  - Response of dental community to family violence issues.

PMID- 9518793
TI  - Development of a preventive dental programme in the Baltic states.

PMID- 9518794
TI  - Economic study of a two chair hygiene system.
AB  - Dental hygiene services play a major role in the economics of a dental practice.
      To survive the financial challenges of the '90s, an office goal should be to
      improve and increase hygiene productivity. The purpose of this study is to
      determine the economic value of a "Two Chair Hygiene System" in a dental office.
      The study was conducted in two separate, three month periods. In one three month
      period, data was collected for one hygienist working one chair. This was called
      the "One Chair Hygiene System". During the second three month period, data was
      collected for one hygienist working two chairs with an assistant; called the "Two
      Chair Hygiene System". The results demonstrate that a "Two Chair Hygiene System"
      is of economic benefit to a dental practice. The findings show an increase in the
      hourly hygiene production, the hourly hygiene salary and in the number of
      patients treated per hour. There was a decrease in the amount of hygienist time
      required per appointment due to efficient delegation to the assistant. The total
      office salary cost remained constant. The results of the study suggest a "Two
      Chair Hygiene System" is an efficient method of delivering hygiene services.

PMID- 9518795
TI  - A workshop approach to enhancing the quality of dental hygiene care. Presented at
      the 12th International Symposium on Dental Hygiene, The Hague, Netherlands, July
      2, 1992.

PMID- 9518796
TI  - Percutaneous injuries and the concern of HIV transmission.

PMID- 9518797
TI  - Family violence: a problem with relevance for the dental hygienist.
AB  - Family violence is a societal reality that affects us all. Dental hygienists
      should be aware that the primary victims of abuse are women, children and older
      adults. The hygienist has a role to play in recognizing the clinical
      manifestations of abuse because the majority of physical injuries sustained
      involve the head and neck. Upon recognition and after clear and concise
      documentation in the chart, dental hygienists should ACT. The law clearly states
      that reporting child abuse is mandatory for persons in positions of authority
      such as teachers, police officers and health care professionals, consequently, it
      is the legal responsibility of all hygienists. There is also moral responsibility
      to victims of abuse. The dental hygienist can initiate discussion on this topic
      at work and be instrumental in establishing office protocol to deal with
      recognized victims of abuse. Although efforts on the part of dental hygienists
      may not stop abuse within families, they truly can make a difference!

PMID- 9518798
TI  - The role of the dental hygienist in a multicultural society. Review of literature
      1988-1993.
AB  - As Canada's population becomes increasingly more diverse, dental hygienists must
      face the challenge of providing culturally sensitive health care. This literature
      review provides a sample of cultural and professional beliefs/values, traditional
      oral hygiene practices and psycho-social determinants that can affect the
      delivery of dental health services. The paper concludes by addressing some of the
      personal, professional and research implications of multicultural diversity for
      the dental hygiene profession.

PMID- 9518799
TI  - Qualitative research, education, and dental hygiene.

PMID- 9518800
TI  - An extended care facility--Mouthcare Project--CFDE report.

PMID- 9518801
TI  - Restorative dental services and Manitoba dental hygienists.
AB  - The purpose of this paper was to discover the attitudes and level of restorative
      dental services provided by dental hygienists in Manitoba. Part one included six
      confidential interviews; three with dentists who had dental hygienists providing
      restorative dental services in their offices on some basis, and three with
      dentists who had dental hygienists practising in their traditional periodontal
      roles only. The second part was a survey designed to determine how many dental
      hygienists provide restorative dental services and what are their attitudes
      towards these services. Also investigated was the attitude of those dental
      hygienists who do not provide these services. Surveys were mailed to two hundred
      randomly selected, licensed, Manitoba dental hygienists, including a survey for
      their employing dentists. Confidential interviews were structured from the
      formatted survey which had yet to be distributed to the participants. The dental
      hygiene surveys were statistically analyzed for demographics and types of
      restorative dental services provided. Open-ended questions in the survey were
      categorized and tabulated. There was a fifty percent completed survey response
      rate from dental hygienists. Fifty-two dentists completed the survey. Thirty-nine
      percent of the surveyed dental hygienists never provide restorative dental
      services, while ten percent provide restorative dental services on a daily basis.
      From the dentists surveyed fifty-six percent of respondents had at some point
      worked in a practice where a dental hygienist provided restorative dental
      services. In conclusion, the authors determined that there is greater utilization
      of restorative services provided by dental hygienists than perceived. Also, most
      dental hygienists felt that their knowledge of dental materials and restorative
      skills enhanced their overall client care.

PMID- 9518802
TI  - Bloodborne pathogens in the health care setting: risk for transmission.

PMID- 9518803
TI  - Report on seniors' dental care. Past experience and future challenges.
AB  - After attending the CDHA North American Research Conference held in Niagara Falls
      last October, Ms. Bowes says she found a significant amount of interest in the
      area of geriatric care being expressed by those in attendance. Consequently, when
      she returned home, she decided to offer CDHA members an opportunity to gain some
      insight on this topic from her own experiences. Although no 'formal' report
      summarizing the findings noted here was ever forwarded to the facilities
      involved, Ms. Bowes says that "some of the information gathered has been used in
      documents and reports that were forwarded to the Ministry of Health and the local
      Board of Health for Simcoe County." The purpose of this report is to alert dental
      professionals to the future dental needs of our rapidly aging population and to
      perhaps assist those who are considering the provision of the elderly by
      outlining my personal experience.

PMID- 9518804
TI  - The communication imperative: a critical thinking paradigm.
AB  - The communication imperative is a recognition of the fact that the interpersonal
      relationship between the health care provider and the client is as fundamental to
      building and maintaining a practice as is clinical skill. At the University of
      Alberta we have introduced a Critical Thinking Module in an attempt to focus on
      this relationship and to encourage students to examine their beliefs and
      attitudes in a new way. This article will examine some of the background to this
      decision as well as look at the course itself.

PMID- 9518805
TI  - The importance of communication to dental hygiene practitioners: skills in
      empathy and understanding of the client.

PMID- 9518806
TI  - Do the eating habits of anorexics and bulimics have an effect on their oral
      health?

PMID- 9518807
TI  - Subepithelial connective tissue grafts.

PMID- 9518808
TI  - National certification: a vital component of quality assurance.

PMID- 9518809
TI  - Dental hygienists are not immune: wife assault as a workplace issue in dental
      practice.

PMID- 9518810
TI  - Guided tissue regeneration.

PMID- 9518811
TI  - Diagnostic considerations in oral papillomatous lesions--case reports of focal
      epithelial hyperplasia.

PMID- 9518812
TI  - Keys to successful handpiece maintenance.
AB  - The purpose of this paper is to assist those individuals involved in maintaining
      dental handpiece systems. Proper preparation and handling of the instruments both
      before and after sterilization is critical to their longevity and performance.
      Asepsis guidelines and protocols are presented as well as references to the major
      handpiece manufacturers. Sterilization systems are discussed to assist in making
      decisions regarding the use of sterilizers best suited to dental handpieces.

PMID- 9518813
TI  - Nursing caries and fluoride varnish.

PMID- 9518814
TI  - A membrane and graft technique for ridge maintenance using high-density
      polytetrafluoroethylene membrane (n-PTFE) and hydroxylapatite: report of four
      cases.

PMID- 9518815
TI  - Overtreatment or appropriate treatment?

PMID- 9518816
TI  - A survey: Texas dental hygienists' demographic and salary data.

PMID- 9518817
TI  - Dental clinical examining board dilemma.

PMID- 9518818
TI  - Managed care: impact on younger dental practitioners in Texas.

PMID- 9518819
TI  - "Is it cancer"?

PMID- 9518820
TI  - Provision of free and discounted dental services to selected populations: a
      survey of attitudes and practices of dentists attending the 1996 Dallas Midwinter
      Meeting.
AB  - An attitudes and practices survey of dentists attending the Dallas Midwinter
      Meeting in January 1996 in Dallas was conducted as a collaborative effort between
      the Dallas County Dental Society and the Baylor College of Dentistry. The survey
      was developed to help determine participating dentists' attitudes and practices
      in the area of provision of dental services on a discounted or free basis to
      disadvantaged patient groups. A total of 225 dentists responded to the survey. Of
      these surveyed dentists, 213 (94.6%) were in private practice and 199 (88.4%)
      described themselves as general dentists. A considerable amount of charitable
      dental services, discounted and free, was reported to be provided by the group of
      respondent dentists. A total of 152 (67.6%) of the dentists surveyed reported
      providing discounted or free care to elderly patients with low income, 125
      (55.6%) provided such care to low-income patients without age restriction, and
      137 (60.9%) cared for patients of record with temporary financial hardship. In
      other patient categories, 79 (35.1%) of the dentists provided free/discounted
      services to handicapped persons and 47 (20.9%) provided care to homebound
      patients. These findings concerning charitable practices by dentists were similar
      to those found in a comparable survey conducted by the American Dental
      Association in 1994. Dentists were fairly evenly split as to their preference
      where to volunteer services. Of the total respondents, 84 (40.6%) preferred
      providing services in their own office and 91 (44.0%) preferred to do so at a
      community health clinic that hosted volunteers.

PMID- 9518821
TI  - Submargination of a resin luting cement--a clinical case report.
AB  - The purpose of this case report was to examine the marginal integrity of an
      indirect inlay and an onlay luted with resin luting cement over a four year
      period. A technique to seal the occlusal margins of the inlay restoration was
      reported. Over time, the occlusal margins of the inlay were noticeably
      submarginated due to wear degradation of the resin inlay cement. The onlay
      margins were less affected by wear. Clinical techniques to overcome
      submargination problems were discussed.

PMID- 9518822
TI  - Soft tissue management: is it a help or hindrance in modern esthetic and
      regenerative periodontics?

PMID- 9518823
TI  - An overview of the new Dental Practice Act.

PMID- 9518824
TI  - Clinical requirements and the dental school blues.

PMID- 9518825
TI  - Pilocarpine, an old drug; a new formulation.
AB  - This article is intended to familiarize dental practitioners with a new drug
      preparation, Salagen, which is specifically indicated for treatment of dry mouth.
      Salagen, an oral form of the drug pilocarpine, is a parasympathetic agonist which
      causes widespread effects on many vital tissues and organs, including the heart,
      blood vessels, smooth muscle, and exocrine glands. The safety and efficacy of
      pilocarpine relies greatly on the accurate diagnosis of the underlying cause of
      dry mouth and an understanding of its mechanism of action. The purpose of this
      article is to provide dental practitioners with a brief review of the physiology
      of salivary secretion and the pharmacology of pilocarpine, including its
      mechanism of action. It is hoped that this information will provide a better
      understanding of the appropriate use of this medication.

PMID- 9518826
TI  - New drugs and drug products from 1995.

PMID- 9518828
TI  - Ethical practice--the role of organized dentistry.

PMID- 9518827
TI  - "Bad news bearers".

PMID- 9518829
TI  - Reconstruction of an atrophic edentulous maxilla with unilateral cleft lip and
      palate (UCLP) using sub-antral augmentation and osseointegrated implants: case
      report and 3-year follow-up.
AB  - With the current sophisticated, multidisciplinary approach to the treatment of
      cleft palate, it is anticipated that most patients with this deformity will enjoy
      good dental health and function. However, due to the number of older adults who
      were not treated with primary bone grafting and orthodontic therapy, there
      remains a significant number of potential candidates who may benefit from dental
      implants and implant-supported prostheses. Although it was not necessary in this
      case, a pharyngeal extension may be added to the maxillary denture to further
      improve speech and deglutition. This case report presents a three-year follow-up
      of a complex reconstruction of a highly compromised, edentulous patient. Stable
      fixation of the maxillary prosthesis results in a complete return to function in
      an individual for whom traditional dental prosthetics had resulted in ten years
      of failure and frustration. Combining the disciplines of reconstructive surgery
      and implant prosthetics enables the clinician to achieve a predictable result
      (Figures 12 and 13). While this case represents an extreme example, there are
      millions of patients for whom implant dentistry can provide life-changing
      benefits.

PMID- 9518830
TI  - Antitrust and managed care ... the safety zones.

PMID- 9518831
TI  - Confidentiality for an eating disorders patient?

PMID- 9518832
TI  - Texas dentistry: the legacy ... the horizon.

PMID- 9518833
TI  - The TDA Mentorship Program: imparting the heritage to secure the horizon. Texas
      Dental Association.

PMID- 9518834
TI  - Professional ethics and the profession: yesterday, today and tomorrow.

PMID- 9518835
TI  - Texas dental hygienists benefits and satisfaction survey.
AB  - The purpose of this study was to determine the satisfaction and fringe benefits
      of Texas dental hygienists and compare the data to a recent national study. A
      blind survey was forwarded to 5,294 active, licensed dental hygienists to obtain
      data for Texas. Responses were received from 2,172 dental hygienists, a 41
      percent response rate. The greatest number of responses came from the larger
      cities in Texas: Dallas, Houston, Austin, and San Antonio. Fifty-eight percent of
      Texas hygienists receive paid vacation, 25 percent medical insurance, 37 percent
      sick pay, and 26 percent receive some type of retirement. Nationally, the figures
      are higher. The survey also sought to determine satisfaction levels. Most dental
      hygienists are satisfied with their salary (65%), their career (85%), and feel
      secure in their employment (92%), while only 46 percent are satisfied with
      benefits. The survey results are inconclusive for hygienists' in the state of
      Texas based on the 41 percent response rate. Practical information may assist
      employers in recruitment and retention of a dental hygienist into the practice.

PMID- 9518836
TI  - The Texas Dental Association--one hundred and twenty-five years of history.

PMID- 9518837
TI  - The presidents of the Texas Dental Association since 1970.

PMID- 9518838
TI  - The Texas Dental Journal: America's oldest dental periodical.

PMID- 9518839
TI  - Dentistry on the frontier of Texas: from the Spanish explorers to an organized
      profession.

PMID- 9518840
TI  - "You're the doc, I trust you ... just do it"!

PMID- 9518841
TI  - The Dental Oncology Education Program.

PMID- 9518842
TI  - Biopsy--a life saving measure.

PMID- 9518843
TI  - Prevention and management of oral complications associated with cancer therapies:
      radiotherapy/chemotherapy.

PMID- 9518844
TI  - Non-melanoma skin cancer for dentists.

PMID- 9518845
TI  - Nutrition--the primary risk factor that nobody talks about.

PMID- 9518846
TI  - Oral complications in the cancer patient.

PMID- 9518847
TI  - Weighing the risks and benefits of an oral cancer screening.

PMID- 9518848
TI  - Oral malignancies diagnosed in an HIV-dedicated dental clinic.

PMID- 9518849
TI  - "Headache/orofacial pain diagnostic dilemma".

PMID- 9518850
TI  - Precision attachment removable partial dentures.
AB  - Although added preparations and skill are required to provide precision
      attachment removable partial dentures, more favorable esthetics and load
      distribution may outweigh the disadvantages. Basic design principles, categories
      (intracoronal, extracoronal, stud, bar and plunger) and selection of precision
      attachments are reviewed.

PMID- 9518851
TI  - Treatment and management of temporomandibular joint dysfunction (TMJ) with a
      modified removable partial denture.

PMID- 9518852
TI  - Trends in continuing dental education: what's happening in the northeast region?
AB  - Historically, dentists have assumed the individual responsibility for staying
      abreast of innovations in the profession. Prior to 1985, only twelve U.S. dental
      licensing boards regulated or monitored the continuing education activities of
      dentists. Today, however, this number has more than doubled. This article
      examines continuing education regulations that are mandated by the state
      licensing boards which participate in the Northeast Regional Dental Board.
      Continuing dental education standards for dentists are examined with respect to
      minimum credit requirements, qualifying sources of credit, and methods of
      reporting and monitoring continuing education activity.

PMID- 9518853
TI  - What practicing dentists should know about EPSDT. Early and Periodic, Screening,
      Diagnosis and Treatment.
AB  - Dr. Al-Tannir was formerly working as a student intern in the West Virginia
      Bureau of Public Health Division of Dental Health. He is currently the Dental
      Public Health Resident for the Department of Veterans Affairs, VA Medical Center,
      Perry Point, Maryland and Clinical Instructor at the University of Maryland at
      Baltimore Dental School, Department of Oral Health Care Delivery. The purpose of
      this paper is to provide practicing dentists in West Virginia with an overview,
      understanding and appraisal of the Early and Periodic, Screening, Diagnosis, and
      Treatment (EPSDT) dental program. EPSDT is one of the least understood and least
      publicized programs in the Department of Health and Human Resources and is the
      children's preventive health component of Medicaid. West Virginia can meet the
      oral health needs for its children by making dental services, both curative and
      preventive, more available through the EPSDT program. This program can be a
      principal means, if sufficiently utilized, of meeting the oral health care needs
      of West Virginia Children by minimizing financial and attitudinal barriers.

PMID- 9518855
TI  - Tasks and stages of professional growth.
AB  - This paper combines data from two surveys, one in 1986 and one in 1992, which
      used the same instrument. Practice problems, and responses to the problems, were
      found to differ according to the number of years in practice, validating a stage
      explanation of professional growth.

PMID- 9518854
TI  - Cephalosporin vs penicillin.
AB  - The correlation between late infection of an orthopedic prosthesis and a dental
      bacteremia remains controversial. Transient bacteremia does occur after dental
      treatment, usually involving streptococcal bacteria, but many orthopedic surgeons
      choose an anti-staphylococcal agent as their prophylactic antibiotic of choice.
      This article reports the results of a recent survey designed to determine, from
      orthopedic surgeons, antibiotic premedication coverage and, specifically, the
      rationale for a chosen regimen for patients having dental surgery. The responses
      showed no common agreement for the choice of a specific antibiotic and little
      rationale regarding the need for prophylaxis.

PMID- 9518857
TI  - Basic dental-anxiety management.

PMID- 9518856
TI  - A conservative, aesthetic, restorative treatment of a worn dentition.

PMID- 9518858
TI  - Guided tissue regeneration: a seven year post surgical case report.

PMID- 9518859
TI  - Impactions: observe or treat?
AB  - In the modern population, few third molars erupt normally and have a good long
      term prognosis. This paper reviews the etiology and potential pathology of
      impacted teeth, and discusses indications and contraindications for extraction.

PMID- 9518860
TI  - Infection control in dental radiology.
AB  - Although exposure to blood is rare in oral and maxillofacial radiology, contact
      with saliva occurs. Thus the spread of infectious diseases is possible through
      cross-contamination, and specific infection control protocols and unit dosing of
      items are needed. This article outlines rationale for implementing state-of-the
      art infection control procedures; and explains federal standards and guidelines
      with an impact on infection control and occupational safety in dental radiology
      procedures.

PMID- 9518861
TI  - A new information base: integrated and networked computers.

PMID- 9518863
TI  - Protocol for treating the avulsed tooth.
AB  - Avulsion of a tooth requires decisive action by the dental practitioner.
      Replantation of the tooth at the earliest possible time, along with the avoidance
      of further periodontal damage, is paramount to achieving a successful result. The
      accident site, time the tooth is out of the socket, storage media and endodontic
      protocol influence the prognosis. Appropriate endodontic management and tooth
      restoration will ensure long-term success.

PMID- 9518862
TI  - Examination of the dentally traumatized patient.
AB  - A thorough examination of the dentally traumatized patient is the first step in
      arriving at the correct diagnosis and subsequent treatment plan. A medical
      history and evaluation is part of the initial examination along with an oral exam
      during which detailed information is recorded.

PMID- 9518864
TI  - Temporomandibular dysfunction, chronic orofacial pain and oral motor disorders in
      the 21st century.
AB  - This article describes the various sensory and motor disorders which afflict the
      orofacial region. Such information is essential to the modern dentist who wishes
      to be proficient in the diagnosis of patients with these problems. These
      abnormalities are broadly separated into three groups of pathologic conditions:
      Temporomandibular disorders; chronic orofacial pain disorders; and oral motor
      disorders. Although much more can be said about each reviewed condition, this
      article focuses on the diagnostic features of each specific disorder within each
      of these 3 groups. It suggests alternate nomenclature for each disorder, where
      appropriate. Due to space limitations the article does not cover the procedures
      for management of each disorder, however, the reader is referred to appropriate
      references in this regard. The overall intent of the article is to help the
      dental practitioner recognize and differentiate the above conditions.

PMID- 9518865
TI  - Creating a hygiene profit center.

PMID- 9518866
TI  - Structural bases of vasopressin/oxytocin receptor function.

PMID- 9518867
TI  - Calcium blood level modulates endogenous nitric oxide action: effects of
      parathroidectomy in patients with hyperparathyroidism.
AB  - Platelet cyclic guanosine monophosphate (cGMP) is produced by soluble guanylate
      cyclase (sGC), the activity of which is modulated by the activity of nitric oxide
      (NO) constitutive synthase (cNOS) which, in turn, is activated by a
      calcium/calmodulin complex. In primary hyperparathyroidism (H-PTH) an increase in
      platelet free calcium levels is present. In this study we evaluate the platelet
      cGMP levels, as an expression of NO production, in the presence of 3-isobutyl-1
      methylxanthine (IBMX) alone (IBMXcGMP) and after stimulation by ionomycine (IONO;
      IONOcGMP) and sodium nitroprusside (SNP; SNPcGMP), in eight subjects affected by
      H-PTH before and after removal of adenoma. Platelet cGMP levels were also
      measured in seven normal subjects. IBMXcGMP and IONOcGMP were elevated in H-PTH
      patients compared with normal subjects (1.9 +/- 0.3 vs 0.8 +/- 0.2 fmol/10(6)
      platelets and 2.7 +/- 0.4 vs 1.4 +/- 0.3; P < 0.02 and P < 0.05 respectively) but
      SNPcGMP was unaffected (3.9 +/- 0.6 vs 2.5 +/- 0.5). After parathyroidectomy,
      blood levels of intact parathyroid hormone (i-PTH), total calcium (t-Ca),
      IBMXcGMP and IONOcGMP all decreased (177.5 +/- 23.9 vs 45.0 +/- 8.8 pg/ml, P <
      0.005; 6.5 +/- 0.5 vs 4.6 +/- 0.1 mEq/1, P < 0.005; 1.9 +/- 0.3 vs 0.8 +/- 0.2, P
      < 0.005; 2.7 +/- 0.4 vs 1.8 +/ 0.3, P < 0.05 respectively), while SNPcGMP was not
      modified (3.9 +/- 0.6 vs 4.3 +/- 0.9). t-Ca and i-PTH were directly correlated
      with IBMXcGMP (P < 0.02, rs = 0.613; P < 0.02, rs = 0.576 respectively) and i-PTH
      was also correlated with t-Ca (P < 0.001), rs = 0.840). IN CONCLUSION: (1) levels
      of IBMXcGMP and IONOcGMP are high in subjects with H-PTH; (2) after surgery both
      IBMXcGMP and IONOcGMP decrease to normal values. As IBMXcGMP expresses basal cGMP
      and IONOcGMP expresses the cGMP after cNOS stimulation, it can be speculated that
      the increase in NO production could be a mechanism to downregulate the
      vasoconstriction which may be caused by the high calcium levels in smooth muscle
      cells. After surgery, together with the normalization of calcium levels, NO
      production also returned to normal values.

PMID- 9518868
TI  - Gastric inhibitory polypeptide and effects of glycation on glucose transport and
      metabolism in isolated mouse abdominal muscle.
AB  - This study investigates the effects of gastric inhibitory polypeptide (GIP) and
      glycated GIP (glucitol adduct of GIP) on glucose uptake and metabolism in muscle.
      Glycated GIP (molecular mass 5147.2 Da) was purified by HPLC following in vitro
      incubation under hyperglycaemic reducing conditions (24 h at pH 7.4). GIP (10(
      10)-10(-8) mol/l) significantly stimulated (1.4- to 1.5-fold, P < 0.001) 2-deoxy
      D-[1-3H]glucose uptake in abdominal muscle pieces from 3- to 5-week-old lean mice
      compared with control incubations (without GIP). This stimulatory effect on
      glucose uptake at 10(-10)-10(-9) mol/l was decreased by 13-20% following
      glycation of the peptide (P < 0.05). GIP (10(-9) and 10(-8) mol/l) induced a
      stepwise 1.4- to 1.7-fold increase (P < 0.01, P < 0.001 respectively) in
      [14C]glucose oxidation compared with controls. This effect on glucose oxidation
      was diminished by 32% with 10(-8) mol/l glycated GIP (P < 0.05). GIP (10(-9) and
      10(-8) mol/l) induced a 1.4- to 1.8-fold increase in [14C]glucose incorporation
      into muscle glycogen (glycogenesis) compared with controls. Glycated GIP (10(-8)
      mol/l) exhibited a 41% decrease in glycogenic activity (P < 0.01). GIP (10(-10)
      10(-8) mol/l) stimulated lactate production in isolated abdominal muscle (1.2- to
      1.3-fold, P < 0.05); however glycated GIP did not exert a significant effect.
      This study demonstrates for the first time that GIP promotes glucose uptake,
      glucose oxidation and glycogenesis in muscle tissue. Furthermore, modification of
      GIP through glycation diminishes its biological effectiveness.

PMID- 9518869
TI  - Serotonin depletion does not alter lipopolysaccharide-induced activation of the
      rat paraventricular nucleus.
AB  - We have investigated the effects of serotonin depletion on immune-mediated
      activation of the hypothalamo-pituitary-adrenal (HPA) axis. Corticotrophin
      releasing factor (CRF) mRNA, c-fos mRNA and Fos peptide responses in the
      paraventricular nucleus (PVN) together with circulating levels of corticosterone
      were assessed in response to i.p. injections of three doses of lipopolysaccharide
      (LPS) both in control animals and animals pretreated with p-chlorophenylalanine
      (PCPA). Conscious animals received either an i.p. injection of 0.5 ml saline or
      200 mg/kg PCPA in 0.5 ml saline on 2 consecutive days. This treatment resulted in
      a 93% depletion of serotonin on the fourth day. On day 4, animals received i.p.
      injections of LPS (2.5 mg/0.5 ml saline, 250 micrograms/0.5 ml or 50
      micrograms/0.5 ml; E. coli 055:B5), or saline injections as controls.
      Pretreatment with PCPA had no effect on the basal levels of corticosterone, or on
      the elevated levels induced by the three doses, of LPS. Fos peptide and c-fos
      mRNA were undetectable in control animals, and Fos-like immunoreactivity
      increased in a dose-dependent manner following i.p. LPS in both control and PCPA
      pretreated animals. C-fos mRNA expression induced by LPS was unaffected by
      serotonin depletion. Following the lowest dose of LPS, CRF mRNA did not change
      above control levels, however, the medium and high doses of LPS produced a
      significant (P < 0.05) increase in CRF mRNA levels in both depleted and intact
      animals. To confirm the temporal effects of serotonin depletion on activation of
      the HPA axis we collected plasma at 30 min, 1, 2, 3, 4, 5, and 6 h after LPS in
      both intact and serotonin-depleted animals. No significant differences in plasma
      corticosterone levels were found at any of the time points between intact and
      depleted animals. It appears that, at least under these experimental conditions,
      serotonergic inputs do not seem to play a major role in mediating the effects of
      LPS on changes in mRNA levels in the PVN or on the subsequent activation of the
      HPA axis.

PMID- 9518870
TI  - Participation of intraluteal progesterone and prostaglandin F2 alpha in LH
      induced luteolysis in pregnant rat.
AB  - We examined the participation of the intraluteal levels of progesterone (P4) and
      prostaglandin F2 alpha (PGF2 alpha) in the induction of luteolysis by LH and its
      relationship with the induction of the 20 alpha-hydroxysteroid dehydrogenase
      activity (20 alpha-HSD). Subcutaneous administration of four doses of 10
      microgram ovine LH (oLH) at 0800, 0900, 1000 and 1100 h on day 19 of pregnancy
      induced a decrease in the activity of the enzyme 3 beta-HSD 24 and 48 h after
      treatment and an increase in luteal 20 alpha-HSD activity 48 h after oLH
      treatment when compared with control rats. Intraluteal and serum P4 levels were
      lower than control values 24 and 48 h after oLH treatment, with a significant
      increase in luteal PGF2 alpha content and a decrease in corpus luteum (CL) weight
      48 h after oLH treatment. Intrabursal ovarian (i.b.) treatment with an inhibitor
      of PG's biosynthesis (diclofenac) (70 microgram/ovary) or P4 (3 microgram/ovary)
      on day 20 of pregnancy, prevented the increase in 20 alpha-HSD activity observed
      48 h after oLH treatment, without any effect on 3 beta-HSD activity. The i.b.
      administration of P4 prevented the increase in intraluteal PGF2 alpha content
      induced by oLH treatment and the increases in 20 alpha-HSD activity and
      intraluteal PGF2 alpha content observed in control animals on day 21 of
      pregnancy. The inhibition of PG biosynthesis also prevents the decrease in
      intraluteal and serum P4 level induced by oLH. These results provide good
      evidence of the important participation of intraluteal P4 and PGF2 alpha on the
      oLH-induced luteolysis in pregnant rats. We also found the P4 produced by the CL
      is involved, in part, in the regulation of luteal PG synthesis. Thus, the early
      decline in 3 beta-HSD activity and the consequent fall in intraluteal P4 content,
      may trigger the synthesis of PGs and thereafter the increase in luteal 20 alpha
      HSD activity to establish luteolysis.

PMID- 9518871
TI  - Melatonin receptors in the human fetal kidney: 2-[125I]iodomelatonin binding
      sites correlated with expression of Mel1a and Mel1b receptor genes.
AB  - Melatonin receptors in the human fetal kidney were identified and characterized
      by quantitative in vitro autoradiography using the melatonin agonist, 2
      [125I]iodomelatonin. Specific binding was localized to cells in the nephrogenic
      region at the outer perimeter of the developing kidney and was time-dependent,
      saturable and inhibited in the presence of guanosine 5'-0-(3-thiotriphosphate)
      indicative of a G protein-coupled receptor. Expression of the Mel1a and Mel1b
      melatonin receptors in human fetal kidney was determined using RT-PCR. In situ
      hybridization confirmed the localization of the Mel1a mRNA transcripts. A role
      for melatonin in development of the human fetal kidney is postulated.

PMID- 9518872
TI  - Activin-A stimulates hypothalamic gonadotropin-releasing hormone release by the
      explanted male rat hypothalamus: interaction with inhibin and androgens.
AB  - The presence of activins in those hypothalamic regions containing gonadotropin
      releasing hormone (GnRH)-secreting neurons suggests that these peptides may
      regulate the reproductive function modulating not only pituitary FSH release and
      biosynthesis, but also hypothalamic GnRH release. The purpose of this study was
      to evaluate the effects of activin-A, a homodimer of inhibin beta A subunit, on
      hypothalamic GnRH release in vitro and, because of their well known antithetical
      effects, to evaluate its interaction with inhibin. In addition, since androgens
      modulate the release of GnRH from male rat hypothalami, we thought it of interest
      to study the possible interplay between these steroids and activin on GnRH
      release. To accomplish this, we employed a hypothalamic organ culture system
      which enabled us to evaluate GnRH release from individually incubated hemi
      hypothalami explanted from male rats. Activin-A stimulated GnRH release in a
      biphasic manner. The maximal effect was reached at a concentration of 10 ng/ml
      which increased GnRH output by about 75%. Inhibin abolished the stimulatory
      effect of a maximally effective concentration of activin-A in a dose-dependent
      manner, whereas alone it had no effect on GnRH output. As previously shown,
      testosterone (1 nmol/l) and dihydrotestosterone (DHT, 0.1 nmol/l) suppressed
      basal GnRH release, but only testosterone was able to inhibit the release of GnRH
      stimulated by activin-A. Since DHT is a non-aromatizable androgen, we evaluated
      whether the inhibitory effect of testosterone was due to its in vitro conversion
      into 17 beta-estradiol. The addition of 4-hydroxyandrostenedione, a steroidal
      aromatase inhibitor, did not influence the suppressive effect of testosterone on
      GnRH release stimulated by activin-A. In conclusion, activin-A stimulated
      hypothalamic GnRH release in vitro and this effect was abolished by inhibin and
      was blunted by testosterone. These findings suggest that activins may participate
      in the regulation of the hypothalamic-pituitary-gonadal axis by modulating GnRH
      release. The ability of testosterone to suppress the release of GnRH stimulated
      by activin-A indicates that this steroid has a potent negative feedback influence
      on GnRH release.

PMID- 9518873
TI  - Development, validation and application of an ultra-sensitive two-site enzyme
      immunoassay for human follistatin.
AB  - Recent studies have found follistatin to be an important regulator of activin
      bioactivity. Whilst a number of assay formats have been described, all are of
      limited sensitivity and require the use of isotopes. Many use polyclonal
      antibodies. Furthermore, a wide range of follistatin preparations have been used
      as standards, complicating inter-laboratory comparison. We now describe an ultra
      sensitive two-site enzyme immunoassay using a pair of mouse monoclonal antibodies
      raised against follistatin 288. The presence of sodium deoxycholate and Tween 20
      in the diluent gave results for total (free and activin-dissociated) follistatin.
      The assay had a detection limit of <19 pg/ml and recovery of spiked follistatin
      288 from amniotic fluid, serum seminal plasma, human follicular fluid and
      granulosa cell conditioned medium averaged 100.7 +/- 7.5%, 89.1 +/- 5.5%, 98 +/-
      4.9%, 96 +/- 7.2% and 123.9 +/- 11% respectively. The intra- and interplate
      coefficients of variation were < 5%. An excess of activin-A (50 ng/ml) prior to
      assay did not affect follistatin recovery. Inhibin-A, inhibin-B, activin-A,
      activin-B and activin-AB had minimal cross-reactivity (<0.3%). However,
      follistatin 315 had a significant cross-reaction (9.9%). Serially diluted human
      samples gave dose-response curves parallel to the standard. Pooled human
      follicular fluid contained high concentrations of follistatin (approximately 242
      ng/ml). Follistatin was also found in maternal serum during pregnancy (first
      trimester approximately 0.8 ng/ml, third trimester approximately 2.8 ng/ml),
      normal male serum (approximately 0.45 ng/ml), amniotic fluid (sixteen week
      approximately 3.63 ng/ml, term approximately 0.89 ng/ml), seminal plasma (2.4-30
      ng/ml) and human granulosa cell conditioned media (approximately 0.44 ng/ml).
      Serial serum samples taken throughout the menstrual cycle of ten women showed
      fluctuating follistatin concentrations (approximately 0.62 ng/ml) with no
      apparent relationship to the stage of the cycle. Interestingly, pooled serum from
      postmenopausal women appeared to have higher follistatin levels than any of the
      normal women (approximately 1.4 ng/ml). The possible presence in certain samples
      of mixtures of follistatin isoforms with different immunoreactivities poses major
      problems of interpretation in this and all other current follistatin
      immunoassays. Further work is needed to identify the major immunoreactive forms
      in different tissues and fluids. Nevertheless, the new assay has a number of
      advantages over previous assays and should prove a useful tool for various
      clinical and physiological studies.

PMID- 9518874
TI  - DNA synthesis by ovine mammary alveolar epithelial cells: effects of heparin,
      epidermal growth factor-related peptides and interaction with stage of pregnancy.
AB  - Amphiregulin is a heparin-binding member of the epidermal growth factor (EGF)
      family, which we have recently shown to be expressed in sheep mammary gland.
      Uniquely among known EGF-like growth factors, its mitogenic activity is inhibited
      by soluble heparin, but heparin-like molecules on the cell surface and/or in
      extracellular matrix appear to be necessary for amphiregulin to exert its
      biological effect. In primary cultures of sheep mammary alveolar epithelial
      cells, heparin (1-20 mg/l) inhibited DNA synthesis in a dose-dependent manner.
      The extent of the inhibition was influenced by physiological state, being greater
      (P < 0.05) in mammary cell cultures derived from 5- to 10-week pregnant sheep
      (63.1 +/- 8.2%, mean +/- S.E.M., n = 8) than in cultures derived from sheep which
      were non-pregnant (35.8 +/- 8.3% inhibition, n = 6) or late, 20-week, pregnant
      (39.8 +/- 5.6%, n = 6). Both EGF and transforming growth factor-alpha (TGF-alpha)
      significantly (P < 0.001) increased DNA synthesis in the presence of heparin. The
      effect of TGF-alpha was dose-related, wholly reversing the inhibitory effect of
      heparin in cell cultures from non-pregnant and 20-week pregnant sheep. DNA
      synthesis was stimulated by amphiregulin and TGF-alpha increased the maximum
      response. The heparin antagonist, hexadimethrine, inhibited DNA synthesis, but,
      in the presence of amphiregulin, approximately equivalent concentrations of
      heparin overcame this inhibitory effect. In the presence of heparin, TGF-alpha
      showed synergistic interactions with insulin or IGF-I. The results indicate
      interactive effects of EGF and IGF growth factor families in sheep mammary
      growth.

PMID- 9518875
TI  - Expression of the crustacean hyperglycaemic hormones and the gonad-inhibiting
      hormone during the reproductive cycle of the female American lobster Homarus
      americanus.
AB  - Crustacean reproduction is regulated by a complex chain of hormonal interactions
      in which the crustacean hyperglycaemic hormones A and B (CHH-A and CHH-B) and the
      gonad-inhibiting hormone (GIH) play a primary role. These neurohormones are
      produced in the same neuroendocrine cells of the X-organ sinus gland complex,
      situated in the eyestalks of the American lobster, Homarus americanus. In order
      to obtain more information on the synthesis, storage, release and function of
      these three neuropeptides during the reproductive cycle, we studied the levels of
      their mRNAs in the X-organ, their peptide storage in the sinus gland and their
      concentration in the haemolymph at different stages of the female reproductive
      cycle. A high CHH-A mRNA level was found only in the previtellogenic stage, while
      elevated mRNA levels were determined for CHH-B in the mature as well as the
      previtellogenic stage. High CHH storage levels in the sinus gland were found
      during previtellogenesis. The total amount of CHH (CHH-A plus -B) in the
      haemolymph was significantly higher during maturation. A low level of GIH mRNA in
      the X-organ and a low amount of the GIH I isoform in the sinus gland were found
      only in the immature stage. In contrast, GIH haemolymph levels were high during
      the immature and previtellogenic stages. We conclude that CHH-A and -B are
      involved in triggering the onset of vitellogenesis and that CHH-B in particular
      is responsible for stimulating oocyte maturation before spawning, while GIH
      prevents the start of vitellogenesis in the ovary. Moreover, our results show
      that the balance between the haemolymph levels of the CHHs and GIH may tune the
      synchronization of reproduction and molting during the biannual reproductive
      cycle of the American lobster.

PMID- 9518876
TI  - Effects of food restriction on the responses of the mammary gland and adipose
      tissue to prolactin and growth hormone in the lactating rat.
AB  - Exogenous GH is used extensively in the USA to stimulate milk production in dairy
      cattle but its effectiveness is reduced in undernourished animals. It has been
      proposed that GH increases milk yield by stimulating IGF-I secretion and that
      this IGF-I-response is nutritionally sensitive and thus acts as a 'sensor' of
      energy balance. To investigate this possibility, we placed lactating rats on
      three planes of nutrition, ad libitum, 50% or 25% of ad libitum for 48 h.
      Subgroups of these animals were treated for 48 h with bromocriptine, to suppress
      prolactin secretion, and anti-rat GH, to neutralize GH action. From 24 to 48 h
      some of the treated animals were assessed for their milk yield response to
      prolactin or GH. Food restriction reduced milk yield in control rats by
      approximately 50% and was accompanied by a catabolic state, as judged by lipid
      mobilization from adipose tissue and by low concentrations of serum insulin, IGF
      I, triiodothyronine and thyroxine, and increased serum nonesterified fatty acid
      concentrations. In animals fed ad libitum, anti-rat GH plus bromocriptine
      treatment produced an 80% decrease in milk yield and a dramatic fall in the
      activity of acetyl-CoA carboxylase in mammary tissue. GH was able to stimulate
      milk yield when given from 24 to 48 h; however, its effectiveness decreased
      progressively as food intake was reduced. The milk yield response to GH was
      accompanied by an increase in serum IGF-I concentrations and this response also
      decreased progressively with reduction of food intake, consistent with the
      hypothesis that IGF-I determines the milk yield response to GH and thus regulates
      GH action on the mammary gland in a nutritionally dependent fashion. However, the
      milk yield response to prolactin and the milk yield of control rats decreased in
      line with food intake without any changes in serum IGF-I concentrations. This
      clearly indicates that factors other than IGF-I are responsible for restricting
      milk yield. In order to assess other possible candidates for this role, we
      monitored serum glucose, non-esterified fatty acids, insulin triiodothyronine and
      thyroxine concentrations, but found no evidence for any simple relationship
      between these parameters and the milk yield response to prolactin and GH.
      Surprisingly we found that the ability of GH or prolactin to prevent epithelial
      cell loss in in the mammary gland was completely insensitive to nutrient intake,
      despite the fact that IGF-I is considered to be an important survival factor for
      mammary epithelial cells. Finally, we also demonstrated that, at least during
      short-term food restriction, the lactating rat is capable of mobilizing
      significant amounts of lipid from adipose tissue, such that it could provide the
      total output of triglyceride in milk, which is much greater than has previously
      been proposed.

PMID- 9518877
TI  - Influence of maternal dexamethasone administration on thermoregulation in lambs
      delivered by caesarean section.
AB  - We have previously shown that lambs delivered by caesarean section 1 week
      prematurely become hypothermic due to reduced brown adipose tissue function in
      conjunction with low plasma concentrations of cortisol and thyroid hormones. The
      present study therefore aimed to determine whether maternal dexamethasone (a
      synthetic corticosteroid) administration could improve thermoregulation in
      premature lambs to the extent that they become similar to term lambs. Lambs were
      either delivered by caesarean section into a warm (30 degrees C; WD) or cool (15
      degrees C; CD) ambient temperature at 140 days of gestation, 2 days after
      maternal dexamethasone treatment, or at 146 days for controls. During the first
      30 min of life the decline in colonic temperature was greater in dexamethasone
      treated lambs compared with controls delivered into the same ambient temperature.
      All lambs then restored colonic temperature although this adaptation took longest
      in dexamethasone treated lambs CD but these subsequently attained highest plateau
      colonic temperatures. Oxygen consumption, breathing frequency and plasma free
      fatty acid concentrations were highest in dexamethasone treated lambs CD. There
      were no differences in plasma thyroid hormones between groups, but cortisol
      concentrations were lower in dexamethasone treated lambs irrespective of delivery
      temperature. Analysis of brown adipose tissue samples at 6 h of life demonstrated
      that dexamethasone treated lambs WD had more uncoupling protein and, in both
      dexamethasone treated and control lambs, uncoupling protein content was higher in
      lambs CD compared with those WD. An effect of ambient temperature on thermogenic
      activity was only observed in the dexamethasone treated group. It is concluded
      that maternal dexamethasone treatment can significantly improve thermoregulation
      after birth following premature delivery by caesarean section. As a consequence,
      dexamethasone treated lambs delivered 1 week prematurely do not remain
      hypothermic and have higher or similar colonic temperatures compared with
      untreated lambs born 1-2 days before term.

PMID- 9518878
TI  - H2O2 induces apoptosis of pig thyrocytes in culture.
AB  - Apoptosis might be involved in the reduction of the thyroid cell population in
      physiopathological situations such as goitre involution and autoimmune
      deleterious processes. Up to now, little attention has been paid to the apoptotic
      phenomenon in the normal thyroid gland the specialized metabolism of which is
      expected to generate reactive oxygen species. Indeed, thyroid cells have the
      capacity to synthesize H2O2. In this study, we have analyzed the capacity of H2O2
      to trigger apoptosis of pig thyrocytes in culture to try to determine whether
      thyrocytes exhibit a particular resistance to apoptosis induced by an oxidative
      stress. We show that exposure of thyrocytes cultured as monolayers to exogenous
      H2O2 induced cell death with characteristics of apoptosis. The effect of H2O2 was
      concentration-dependent; apoptotic cells were already observed after exposure to
      50 micro M H2O2. At high concentrations (millimolar range), H2O2 exerted toxic
      effects leading to rapid cell disruption. Within the first hour after the onset
      of exposure to 50-300 micro M H2O2, early signs of apoptosis, i.e. DNA
      fragmentation, appeared in a low (0.1-1%) but definite fraction of thyrocytes.
      The proportion of adherent cells exhibiting DNA fragmentation remained fairly
      constant after 6, 15 and 24 h. During the 24-h period, an increasing number of
      cells detached from the culture dish and up to 30-40% of cells in suspension
      displayed apoptotic features. The fraction of cells that lost contact with the
      culture dish amounted to up to 25% 24 h after addition of 300 micro M H2O2. In
      conclusion, as reported for other cell types, low H2O2 concentrations are capable
      of triggering apoptosis in thyrocytes cultured as monolayers. Thyrocytes that
      undergo apoptosis secondarily lose contact with neighbour cells and the
      substratum; cell detachment from the monolayer probably happens within 1-2 h
      after initiation of DNA fragmentation. Our data show that the apoptotic
      commitment can take place many hours after initiation of the oxidative stress.

PMID- 9518879
TI  - Autoregulation of central and peripheral growth hormone receptor mRNA in domestic
      fowl.
AB  - Growth hormone (GH) regulates numerous cellular functions in many different
      tissues. A common receptor is believed to mediate these tissue-specific effects,
      suggesting that post-receptor signalling molecules or tissue sensitivity to GH
      may differ between tissues. Tissue sensitivity depends upon the abundance of GH
      receptors (GHRs), thus tissue-specific GHR regulation could enable tissue
      specific GH actions. The comparative autoregulation of GHR gene transcription in
      central (whole brain or hypothalami) and peripheral (liver, bursa, spleen and
      thymus) tissues was therefore examined in domestic fowl. In all tissues, a 4.4 kb
      GHR gene transcript that encodes the full-length GHR was identified. The
      abundance of this transcript was inversely related to endogenous GH status; it
      was lower in males with high circulating concentrations of GH and higher in
      females with lower basal concentrations of plasma GH. The abundance of this
      transcript was also rapidly downregulated in response to a bolus systemic
      injection of recombinant chicken GH, designed to mimic an episodic burst of
      endogenous GH release. This autoregulatory response was observed within 2 h of GH
      administration and was of greater magnitude in the brain than in peripheral
      tissues. Intracerebroventricular injections of GH also downregulated GHR gene
      expression in the brain, although hepatic GHR transcripts were unaffected 24 h
      after central administration of GH. In contrast, the induction of
      hyposomatotropism by passive GH immunoneutralization increased the abundance of
      the GHR transcript in the thymus, but not in other central (brain) or peripheral
      (bursa, liver) tissues. GH is not the sole regulator of GHR abundance, however;
      hypersomatropism induced by hypothyroidism was associated with an increase in GHR
      mRNA. The expression of the GHR gene in the domestic fowl would thus appear to be
      autoregulated by GH in a tissue-specific way.

PMID- 9518880
TI  - Androstenedione treatment reduces loss of cancellous bone volume in
      ovariectomised rats in a dose-responsive manner and the effect is not mediated by
      oestrogen.
AB  - We have tested the hypothesis that androstenedione (administered as 21-day, slow
      release pellets) is converted to active sex steroids and reduces bone turnover in
      the ovariectomised rat model. We found that ovariectomy resulted in a minor but
      significant reduction in plasma concentrations of androstenedione and
      testosterone and a more significant reduction in oestrone (E1) and oestradiol
      (E2). This was associated with the expected substantial loss of metaphyseal
      cancellous bone volume. Androstenedione (1.5-100 mg) pellets increased the plasma
      concentrations of androstenedione and testosterone above those in the
      ovariectomised (ovx) rats in a dose-responsive manner, whereas E2 plasma
      concentrations were increased to a minor but significant degree above those in
      the ovx animals. Androstenedione reduced loss of cancellous bone volume in a dose
      dependent fashion by reducing bone turnover. The 1.5, 5 and 100 mg
      androstenedione-induced effect on bone turnover was not abrogated by simultaneous
      treatment with Arimidex, an aromatase inhibitor. This implies that the skeletal
      protective effect of androstenedione was not oestrogen-mediated.

PMID- 9518881
TI  - Growth hormone responses to growth hormone-releasing hormone and hexarelin in fed
      and fasted dogs: effect of somatostatin infusion or pretreatment with
      pirenzepine.
AB  - Using unanesthetized young male and female beagle dogs, before and after a 2-day
      fast, we studied the effect of an i.v. infusion of 0.9% saline (5 ml/h),
      somatostatin (SS, 4 or 8 micrograms/kg/h), or pretreatment with pirenzepine (PZ,
      0.6 mg/kg i.v.), a muscarinic cholinergic antagonist which allegedly releases SS,
      on the GH release evoked by acute administration of GHRH (2 micrograms/kg i.v.),
      hexarelin (HEXA), a member of the GH-releasing peptide family (250 micrograms/kg
      i.v.) or GHRH plus HEXA. In fasted dogs, GHRH delivered during saline infusion
      induced a clear-cut rise in plasma GH levels, significantly higher than that
      which it induced in fed dogs. In contrast, HEXA, although very effective in
      causing the release of GH, only slightly increased GH secretion in fasted dogs
      over that which it induced in fed dogs. Co-administration of GHRH plus HEXA into
      fed dogs induced a synergic GH response that further increased with fasting. The
      action of GHRH in fed dogs was abolished by the lower dose of SS, whereas SS at
      either dose was ineffective in suppressing the GH-releasing effect during
      fasting. Infusion of the lower dose of SS failed to counter the action of HEXA,
      either before or during fasting, whilst the higher SS dose partially reduced it
      in both conditions. In contrast to SS, PZ reduced the GH-releasing effect of GHRH
      and HEXA, both in the fed state and, though to a lesser extent, during fasting.
      Pirenzepine only slightly reduced the robust GH rise elicited by GHRH plus HEXA
      in fed dogs. The suppressive effect of PZ on the GH response to combined
      administration of the peptides was lowest in fasted dogs. These data show that:
      (1) fasting augmented the GH response to GHRH and (to a lesser degree) to HEXA;
      (2) SS inhibited the GH response to GHRH in the fed state, but not in the fasted
      state; (3) only the higher dose of SS partially reduced the GH stimulation by
      HEXA in either the fed or the fasted state; (4) PZ lowered the GH response to
      GHRH and to HEXA in both the fed and (to a lesser degree) the fasted state; (5)
      PZ did not modify the GH release due to the combined administration of GHRH and
      HEXA. It is suggested that: (1) during fasting the greatly enhanced GH response
      to GHRH alone or GHRH plus HEXA probably reflects an augmented GHRH secretion;
      (2) somatotrope refractoriness to SS may contribute to the enhanced GH secretion
      in states of calorie deprivation; (3) in contrast to a general belief, muscarinic
      cholinergic antagonists, e.g. PZ, do not act exclusively via release of SS, but
      probably also through inhibition of GHRH function.

PMID- 9518882
TI  - Inhibitory effects of 1,25-dihydroxyvitamin D3 and 9-cis-retinoic acid on
      parathyroid hormone-related protein expression by oral cancer cells (HSC-3).
AB  - We investigated the effects of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and 9-cis
      retinoic acid (9cRA) on parathyroid hormone-related protein (PTHrP) production
      and its mRNA expression by the human oral squamous carcinoma cell line (HSC-3).
      The major transcript of PTHrP was 1.5 kb in human HSC-3 cells. In the presence
      and absence of serum, 1,25(OH)2D3 produced dose-dependent inhibition of PTHrP
      gene expression and secretion. Significant inhibition by 1,25(OH)2D3 in the
      presence of serum was observed at 10(-10) M for mRNA expression and 10(-8) M for
      secretion, whereas under serum-free conditions, 1,25(OH)2D3 significantly
      suppressed PTHrP mRNA expression at 10(-10) M and secretion at 10(-9) M. Thus the
      remainder of the experiments were performed under serum-free conditions. After 24
      h of incubation, 9cRA decreased dose-dependently PTHrP mRNA expression and PTHrP
      secretion. Addition of 10(-7) M 1,25(OH)2D3 or 10(-7) M 9cRA to HSC-3 cells
      significantly suppressed PTHrp transcription within 1 h and the PTHrP secretion
      within 12 h. Maximal suppression of mRNA expression was maintained for 12-48 h.
      9cRA caused a continuous decrease in PTHrP secretion for up to 48 h, whereas the
      inhibition of secretion by 1,25(OH)2D3 was transient and abolished by 48 h.
      Neither 1,25(OH)2D3 nor 9cRA altered the stability of PTHrP mRNA. The inhibitory
      effect of 1,25(OH)2D3 and 9cRA on PTHrP mRNA expression was additive, whereas no
      additive effect was observed with regard to PTHrP secretion. These results
      indicate that 1,25(OH)2D3 and 9cRA suppressed PTHrP production and mRNA
      expression in oral squamous cancer cells, and suggest that transcriptional
      suppression may act through binding of the heterodimer (vitamin D receptor
      retinoid X receptor) to negatively responsive elements of the PTHrP gene.

PMID- 9518883
TI  - Effects of corticotropin-releasing factor on feeding and pancreatic polypeptide
      response in the dog.
AB  - We have previously reported that corticotropin-releasing factor (CRF) is a potent
      stimulator of adrenocorticotropic hormone and cortisol secretion in the dog.
      Therefore, in the present study, we investigated the extrahypophysiotropic
      actions of CRF in this species. When CRF was injected into the third cerebral
      ventricle, it failed to inhibit food intake significantly at doses of 1.19, 3.57,
      and 11.9 nmol. This is in sharp contrast with the results in rodents. At the 3.57
      and 11.9 nmol doses, CRF markedly stimulated the secretion of pancreatic
      polypeptide (PP), a hormone under vagal control, and at the highest dose CRF
      increased plasma glucose levels. These results suggest species differences in the
      feeding response to CRF and activation of the parasympathetic nervous system in
      the dog.

PMID- 9518885
TI  - Levels of messenger RNA encoding ovarian receptors for FSH and LH in cattle
      during superovulation with equine chorionic gonadotrophin versus FSH.
AB  - This study tested the hypothesis that luteal LH receptor (LHr) and follicular LHr
      and FSH receptor (FSHr) steady-state mRNA levels are greater during
      superovulation with equine chorionic gonadotrophin (eCG) compared with that with
      FSH. Heifers were stimulated with eCG (n = 10) or FSH (n = 10), and ovaries were
      recovered the day before and at 12 and 24 h after luteolysis was induced with
      prostaglandin F2 alpha (PGF2 alpha). Total RNA was purified from individual
      follicles and corpora lutea. Steady-state levels of LHr and FSHr mRNA were
      assessed by slot blot analysis employing homologous cDNA probes. There were no
      differences in luteal LHr between FSH- and eCG-stimulated animals before
      luteolysis, and hybridization signals were detected in only one of six animals by
      12 h after injection of PGF2 alpha. After PGF2 alpha injection, steady-state
      levels of follicular LHr were 4-fold lower (P < 0.05) and follicular FSHr mRNA
      levels were 2.4-fold lower (P < 0.05) in eCG- compared with FSH-treated cattle.
      In eCG-treated animals, induction of luteolysis led to a significant increase in
      follicular LHr mRNA levels (P < 0.01) and a significant decrease in follicular
      FSHr mRNA levels (P < 0.01). There was no such effect of luteolysis in FSH
      treated animals. We conclude that superovulation with eCG, compared with FSH,
      results in lower follicular levels of LHr and FSHr mRNA but does not affect
      luteal LHr mRNA levels.

PMID- 9518884
TI  - Periovulatory changes in hypothalamic and pituitary monoamines following GnRH
      analogue treatment in the catfish Heteropneustes fossilis: a study correlating
      changes in plasma hormone profiles.
AB  - In Heteropneustes fossilis, administration of a single dose (0.15 micrograms/g
      body weight, i.p.) of [D-Ala6,Gly10]-gonadotrophin-releasing hormone analogue
      (GnRHa) induced ovulation (in 35 of 35 fish) when mild-stripped at 16 h. Plasma
      gonadotrophin II (GTH II) levels showed a highly significant increase at 2, 4, 8,
      12 and 16 h with the peak at 8 h. Plasma cortisol, progesterone and testosterone
      showed significant elevations at 2, 4, 8 and 12 h with peaks at 8 h (cortisol and
      testosterone) and 4 h (progesterone). The levels declined to control values at 16
      and 48 h except that of testosterone which decreased even further. In contrast,
      plasma levels of oestradiol-17 beta decreased significantly at 2, 4, 8 and 12 h,
      with the lowest value at 8 h, but increased at 16 and 18 h. The contents of
      hypothalamic and pituitary serotonin and noradrenaline increased at 8 h,
      coinciding with the peak GTH II rise, and decreased at 16 h. In contrast,
      dopamine content declined at 8 h in both the hypothalamus and pituitary, but
      increased at 16 h only in the hypothalamus. The hypothalamic adrenaline level
      decreased at 8 h but increased significantly at 16 h. Hypothalamic levels of
      monoamine oxidase, catechol O-methyltransferase and dopamine beta-hydroxylase
      were elevated significantly at 8 h; the dopamine beta-hydroxylase activity
      decreased at 16 h. Phenylethanolamine N-methyltransferase activity was elevated
      only at 16 h, coinciding with the rise in adrenaline content. It is inferred that
      the preovulatory decrease in dopamine content concomitant with rises in serotonin
      and noradrenaline levels, triggered by the low titre of oestradiol, might have
      potentiated the GnRHa/GnRH (endogenous)-induced release of GTH II for a prolonged
      period.

PMID- 9518886
TI  - In vivo stimulation of the beta(2)-adrenergic pathway increases expression of the
      Gi proteins and the alpha(2)A-adrenergic receptor genes in the pregnant rat
      myometrium.
AB  - Cross-regulations between Gs and Gi mediated pathways controlling the adenylyl
      cyclase activity have been clearly demonstrated in vitro. To elucidate whether
      activation of the beta-adrenergic pathway in the pregnant myometrium might affect
      Gi proteins and alpha(2)-adrenergic receptors (ARs), we treated late pregnant
      rats from day 18 to day 21 with twice-daily administration of isoproterenol (8
      mg/kg). This treatment increased myometrial cAMP levels and led after 76 h to a
      significant and maximal rise in the immunoreactive amount of myometrial Gi alpha
      2 and Gi alpha 3 proteins (1.4- and 1.7-fold respectively) associated with a
      parallel increase of the steady-state levels of both Gi alpha 2 and Gi alpha 3
      mRNA (1.6- and 1.9-fold respectively). Propranolol antagonized this response
      indicating the implication of the beta-adrenergic pathway. Nuclear run-on assays
      demonstrated that isoproterenol enhanced respectively by 1.3- and 1.2-fold the
      transcription rate of the Gi alpha 2 and Gi alpha 3 genes. Quantification of
      myometrial alpha(2)-ARs by [3H]rauwolscine binding revealed that the total number
      of receptors was also increased at 76 h by 1.7-fold when compared with controls,
      with no change in the affinity of the alpha(2)-ARs for the ligand. This effect
      was antagonized by propranolol. Quantification of both alpha(2A)- and alpha(2B)
      subtypes by Northern blotting analysis demonstrated that this elevation was due
      to a selective increase of the alpha(2A)-subtype mRNAs. The present results
      indicate that in vivo stimulation of the beta-adrenergic pathway by isoproterenol
      increases both Gi alpha 2/Gi alpha 3 and alpha(2A)-AR expression in the pregnant
      rat myometrium. The possible contribution of such a mechanism in pregnancy
      related changes of both entities is discussed.

PMID- 9518887
TI  - Characterisation of kinin receptors on the human isolated umbilical artery.
AB  - The aim of this study was to determine the kinin responses on human umbilical
      artery (HUA) and to characterise the kinin receptors present on this tissue. The
      HUA was found to constrict in response to both the B2 receptor agonist,
      bradykinin (BK), and the B1 receptor agonist, des-Arg9-BK. The presence of
      indomethacin (2.79 microM) was found to have no significant effect on the
      responses to BK and des-Arg9-BK. The presence of the B2 receptor antagonist, HOE
      140 (+2.79 microM indomethacin), resulted in a concentration-related rightward
      displacement of the concentration-effect curves to BK. The antagonism of the
      constrictor responses to BK by HOE-140 was found to be competitive (pA2 = 7.5).
      The responses to BK were not significantly affected by the B1 receptor antagonist
      des-Arg9(leu8)BK. The presence of des-Arg9(leu8)BK (+2.79 microM indomethacin)
      resulted in a concentration-related rightward displacement of the concentration
      effect curve to des-Arg9-BK. The antagonism of the response to des-Arg9-BK by des
      Arg9(leu8)BK was found to be competitive (pA2 = 5.9). The responses to des-Arg9
      BK were not significantly affected by HOE-140. The results of the present study
      suggest that the products of the cyclooxygenase pathway are not involved in the
      kinin constrictor response on HUA and indicate the presence of B1 and B2
      receptors on this tissue.

PMID- 9518888
TI  - Hypersecretion of corticotrophin-releasing hormone and arginine vasopressin in
      hypothyroid male rats as estimated with push-pull perfusion.
AB  - The relationship between hypothyroidism and disturbance of the hypothalamo
      hypophysial-adrenal axis was investigated using adult male rats. Hypothyroidism
      was produced by administration of 4-methyl-2-thiouracil (thiouracil) in the
      drinking water for 2 weeks. Hypothyroidism decreased adrenal weights to 57% of
      controls and plasma concentrations of corticosterone to 48% of controls. The
      changes in the weight of adrenals recovered to control levels by administration
      of thyroxine. The pituitary responsiveness to corticotrophin-releasing hormone
      (CRH) and arginine vasopressin (AVP) for ACTH release markedly increased in
      hypothyroid rats as compared with euthyroid rats. In vivo release of CRH and AVP
      in median eminence significantly increased in hypothyroid rats as compared with
      euthyroid rats. There were no significant differences in hypothalamic
      concentrations of CRH and AVP. These results indicate that hypothyroidism causes
      adrenal dysfunction directly and results in hypersecretion of ACTH mediated by
      increases in synthesis of CRH and AVP in the hypothalamus.

PMID- 9518889
TI  - Expression of oestrogen receptor alpha and beta in rat heart: role of local
      oestrogen synthesis.
AB  - The role of cardiac oestrogen receptor expression and local oestrogen synthesis
      in the pathogenesis of cardiovascular disease is poorly understood. Therefore we
      studied the effects of the oestrogen precursors androstendione and testosterone
      on the expression of cyp450 aromatase, oestrogen receptor alpha and beta, and
      inducible NO synthase (iNOS) in neonatal rat cardiac myocytes. Here, we show that
      cyp450 aromatase is expressed in cardiac myocytes and incubation of cardiac
      myocytes with oestrogen precursors leads to sexual dimorphic transactivation of
      an oestrogen-responsive reporter plasmid. Furthermore, incubation with oestrogen
      precursors stimulated expression of oestrogen receptor alpha and beta, and iNOS
      in a gender-specific fashion. These data suggest that local oestrogen
      biosynthesis of the heart is effective to activate oestrogen receptor alpha and
      beta, and downstream target genes in a gender-based fashion and may therefore
      contribute to the beneficial effects of oestrogen in the pathogenesis of
      cardiovascular disease.

PMID- 9518890
TI  - Early identification of variant Creutzfeldt-Jakob disease.

PMID- 9518891
TI  - Medically unexplained neurological symptoms.

PMID- 9518892
TI  - Not one academy but two.

PMID- 9518893
TI  - At last--maternity statistics for England.

PMID- 9518894
TI  - Drug treatment in heart failure.

PMID- 9518895
TI  - Rewarding healthcare teams.

PMID- 9518897
TI  - British patients can sue tobacco companies.

PMID- 9518896
TI  - Meeting the challenge of genetic advance.

PMID- 9518898
TI  - Asian finance crisis threatens vaccinations.

PMID- 9518899
TI  - Dutch face disclosure of medical records.

PMID- 9518900
TI  - Cervical screening laboratories should be accredited.

PMID- 9518901
TI  - Dolly the sheep was a clone, Edinburgh scientist maintains.

PMID- 9518902
TI  - Very low fat diets may harm some people.

PMID- 9518903
TI  - Canadians win award over breast implants.

PMID- 9518905
TI  - Cancer is main cause of death in Britain.

PMID- 9518906
TI  - Office surgery in Florida to be reviewed.

PMID- 9518907
TI  - Diagnosis of Creutzfeldt-Jakob disease by measurement of S100 protein in serum:
      prospective case-control study.
AB  - OBJECTIVE: To analyse serum concentrations of brain specific S100 protein in
      patients with Creutzfeldt-Jakob disease and in controls. DESIGN: Prospective case
      control study. SETTING: National Creutzfeldt-Jakob disease surveillance unit.
      SUBJECTS: 224 patients referred to the surveillance unit with suspected
      Creutzfeldt-Jakob disease and 35 control patients without dementia. MAIN OUTCOME
      MEASURE: Serum concentration of S100 protein in patients with Creutzfeldt-Jakob
      disease, in patients with other diseases causing dementia, and in the control
      group. RESULTS: Of the 224 patients with suspected Creutzfeldt-Jakob disease, 65
      were classed as definitely having the disease after neuropathological
      verification, an additional 6 were classed as definitely having the disease as a
      result of a genetic mutation, 43 as probably having the disease, 36 as possibly
      having the disease, and 74 patients were classed as having other disease. In the
      108 patients classed as definitely or probably having Creutzfeldt-Jakob disease
      the median serum concentration of S100 was 395 pg/ml (SD 387 pg/ml). This was
      significantly higher than concentrations found in the 74 patients classed as
      having other diseases (median 109 pg/ml; SD 177 pg/ml; P = 0.0001). At a cut off
      point of 213 pg/ml sensitivity for the diagnosis of the disease was 77.8% (95%
      confidence interval 68.8% to 85.2%) and specificity was 81.1% (70.3% to 89.3%).
      There was a significant difference in survival at different concentrations of
      S100 in Kaplan-Meier curves (P = 0.023). CONCLUSION: Measurement of serum
      concentrations of S100 is a valuable tool which can be used more easily than
      tests on cerebrospinal fluid in the differential diagnosis of Creutzfeldt-Jakob
      disease. More studies are needed to determine whether serial testing of serum
      S100 improves diagnostic accuracy.

PMID- 9518908
TI  - Slater revisited: 6 year follow up study of patients with medically unexplained
      motor symptoms.
AB  - OBJECTIVE: To investigate psychiatric and neurological morbidity, diagnostic
      stability, and indicators of prognosis in patients previously identified as
      having medically unexplained motor symptoms. DESIGN: Follow up study. SETTING:
      National Hospital for Neurology and Neurosurgery, London--a secondary and
      tertiary referral hospital for neurological disorders. SUBJECTS: 73 patients with
      medically unexplained motor symptoms admitted consecutively in 1989-91. 35 (48%)
      patients had absence of motor function (for example, hemiplegia) and 38 (52%) had
      abnormal motor activity (for example, tremor, dystonia, or ataxia). MAIN OUTCOME
      MEASURES: Neurological clinical diagnosis at face to face reassessment by a
      neurologist and a psychiatric diagnosis after a standardised assessment interview
      -the schedule for affective disorders and schizophrenia--conducted by a
      psychiatrist. RESULTS: Good follow up data were available for 64 subjects (88%).
      Only three subjects had new organic neurological disorders at follow up that
      fully or partly explained their previous symptoms. 44/59 (75%) subjects had had
      psychiatric disorders; in 33 (75%) patients, the psychiatric diagnosis coincided
      with their unexplained motor symptoms. 31/59 (45%) patients had a personality
      disorder. Three subjects had developed new psychiatric illnesses at follow up,
      but in only one did the diagnosis account for the previous motor symptoms.
      Resolution of physical symptoms was associated with short length of symptoms,
      comorbid psychiatric disorder, and a change in marital status during follow up.
      CONCLUSIONS: Unlike Slater's study of 1965, a low incidence of physical or
      psychiatric diagnoses which explained these patients' symptoms or disability was
      found. However, a high level of psychiatric comorbidity existed.

PMID- 9518909
TI  - Effect of temazepam on oxygen saturation and sleep quality at high altitude:
      randomised placebo controlled crossover trial.
AB  - OBJECTIVE: To determine the effects of temazepam on the quality of sleep and on
      oxygen saturation during sleep in subjects at high altitude. DESIGN: Randomised,
      blinded, crossover, placebo controlled trial. SETTING: Base camp at Mount Everest
      (altitude 5300 m). SUBJECTS: 11 members of British Mount Everest Medical
      Expedition recently arrived at base camp. INTERVENTION: Participants were
      randomly allocated to receive either temazepam 10 mg or placebo on their first
      night at base camp and the other treatment on the second night. MAIN OUTCOME
      MEASURES: Quality of sleep (assessed subjectively), mean arterial oxygen
      saturation value, and changes in saturation values (as measure of periodic
      breathing) while participants taking temazepam or placebo. RESULTS: All
      participants noted subjective improvements in sleep. Mean saturation value
      remained unchanged when temazepam was compared with placebo (74.65% v 75.70%, P =
      0.5437). There were fewer changes in oxygen saturation when participants took
      temazepam and when measured as decreases > 4% below the mean value of saturation
      each hour (P = 0.0036, paired Student's t test (two tailed)). CONCLUSIONS:
      Participants taking temazepam at 5300 m showed no significant drop in mean oxygen
      saturation values during sleep. Both the number and severity of changes in
      saturation during sleep decreased and the quality of sleep improved. This may be
      a result of a reduction in the number of awakenings and might lead to greater
      respiratory stability and fewer episodes of periodic breathing. This has the
      effect of improving the quality of sleep and reducing the number of periods of
      desaturation during sleep.

PMID- 9518910
TI  - Case-control study of risk of cerebral sinus thrombosis in oral contraceptive
      users and in [correction of who are] carriers of hereditary prothrombotic
      conditions. The Cerebral Venous Sinus Thrombosis Study Group.
AB  - OBJECTIVE: To investigate whether users of oral contraceptives and in [corrected]
      carriers of a hereditary prothrombotic condition (factor V Leiden mutation,
      protein C, S, or antithrombin deficiency) have an increased risk of cerebral
      sinus thrombosis. DESIGN: Comparison of a prospective series of cases of cerebral
      sinus thrombosis with population data. SETTING: Neurological teaching hospitals
      from different regions in the Netherlands (cases) and a representative sample of
      the non-institutionalised Dutch population (controls). SUBJECTS: 40 women aged 18
      54 years with cerebral sinus thrombosis (cases) and 2248 women aged 18-49 years
      (controls). MAIN OUTCOME MEASURE: Current use of oral contraceptives at the time
      of the thrombosis (cases) or at the time of the questionnaire (controls).
      Prevalences of a hereditary prothrombotic condition in patients and in the
      population with odds ratios. RESULTS: 34 of 40 (85%) women with cerebral sinus
      thrombosis used oral contraceptives, versus 1007 of 2248 (45%) of the control
      women; the age adjusted odds ratio was 13 (95% confidence interval 5 to 37).
      Seven of 36 patients (19%) had a prothrombotic deficiency, versus 7% expected in
      the population; this corresponds to a threefold to fourfold increase in risk. In
      women who used oral contraceptives and also carried a prothrombotic defect, the
      odds ratio for cerebral sinus thrombosis was about 30 relative to women who had
      neither risk factor. CONCLUSION: The use of oral contraceptives and being a
      carrier of a hereditary prothrombotic condition increase the risk of and interact
      in a multiplicative way in the development of cerebral sinus thrombosis.

PMID- 9518911
TI  - Single photon emission computed tomography in the identification of new variant
      Creutzfeldt-Jakob disease: case reports.

PMID- 9518912
TI  - Social alcohol consumption and low Lp(a) lipoprotein concentrations in middle
      aged Finnish men: population based study.

PMID- 9518913
TI  - Postural hypotension induced by paroxetine.

PMID- 9518914
TI  - Development and evaluation of a community based, multiagency course for medical
      students: descriptive survey.
AB  - OBJECTIVE: To develop and evaluate an effective, community based, multiagency
      course (involving doctors, nurses, non-health statutory workers, and voluntary
      organisations) for all Leicester medical students, in response to the General
      Medical Council's recommendation of preparing the doctors of tomorrow to handle
      society's medical problems. DESIGN: Survey evaluating a task oriented, problem
      solving course, designed by medical students in partnership with the University
      of Leicester and the local community. The students, staff, and participating
      agencies and patients all helped in the evaluation of the first course. The
      students' performance on the course was also individually assessed. SETTING:
      Inner city housing estate with Jarman index 64.1 in Leicester. SUBJECTS: All
      third year medical students at Leicester University. MAIN OUTCOME MEASURES:
      Results of the student assignments and students' responses to a questionnaire.
      Results of feedback questionnaires distributed to the patients and agency
      representatives. RESULTS: In a two month period, 168 students completed the first
      course. 163 students passed the criterion referenced assignment, 50 of whom
      achieved an "excellent" grade. 166 completed the questionnaire, with 159 wishing
      to see the course continue in the present format and 149 saying that the course
      linked theoretical teaching with the practical experiences gained in the
      community. CONCLUSIONS: The University of Leicester has a viable mechanism for
      providing a community based, multiagency course for all its medical students.
      Many of the principles applied in the development and implementation of the
      course could be transferred to other medical schools.

PMID- 9518915
TI  - Recent advances. Immunology.

PMID- 9518916
TI  - Central venous air embolism causing pulmonary oedema mimicking left ventricular
      failure.

PMID- 9518917
TI  - What is Zelen's design?

PMID- 9518918
TI  - ABC of allergies. The epidemiology of allergic disease.

PMID- 9518919
TI  - Why do we need randomised controlled trials to assess behavioural interventions?

PMID- 9518921
TI  - The new genetics in clinical practice.

PMID- 9518922
TI  - Quality issues in continuing medical education.

PMID- 9518920
TI  - Hypertension treatment and control in sub-Saharan Africa: the epidemiological
      basis for policy.

PMID- 9518923
TI  - One fifth of samples of unpasteurised milk are contaminated with bacteria.

PMID- 9518925
TI  - Ethics and international research. Comparison of short and long zidovudine
      regimens is appropriate.

PMID- 9518924
TI  - Ethics and international research. Placebo trials are unethical for established,
      untested treatments.

PMID- 9518926
TI  - Ethics and international research. Zidovudine is too expensive for developing
      countries.

PMID- 9518927
TI  - Ethics and international research. Kenyan statutory body was unaware of study.

PMID- 9518928
TI  - Ethics and international research. Potential enticement of placebo trials needs
      to be debated.

PMID- 9518929
TI  - Ethics and international research. Obtaining informed consent for trials in
      Africa is possible.

PMID- 9518930
TI  - Serum samples in clinical study were manipulated.

PMID- 9518931
TI  - Rebound sodium and water retention occurs when diuretic treatment is stopped.

PMID- 9518932
TI  - Should stroke medicine be a separate subspecialty? Perhaps units should focus on
      clinical problems rather than diseases.

PMID- 9518933
TI  - Should stroke medicine be a separate subspecialty? Stroke services should be
      coordinated by physicians who are expert and interested.

PMID- 9518934
TI  - Should stroke medicine be a separate subspecialty? Future consultants in stroke
      medicine should also rotate through psychiatry.

PMID- 9518935
TI  - Where is scientific evidence supporting EU policy on BSE and pharmaceuticals?

PMID- 9518936
TI  - CJD was not diagnosed until eight months after organ donor's death.

PMID- 9518937
TI  - Acute otitis media in children. Reappraisal of management of acute otitis media
      is required.

PMID- 9518938
TI  - SSRIs may well be best treatment for elderly depressed subjects.

PMID- 9518939
TI  - Writing to authors of systematic reviews elicited further data in 17% of cases.

PMID- 9518940
TI  - Trial of prescribing strategies for sore throat. Complications of sore throat are
      not rare.

PMID- 9518941
TI  - Nutrition and health.

PMID- 9518942
TI  - Ten commandments for the care of terminally ill patients.

PMID- 9518943
TI  - Stable coronary artery disease.

PMID- 9518944
TI  - Primary mediastinal germ cell tumor in HIV infection.

PMID- 9518945
TI  - Famciclovir and valacyclovir.

PMID- 9518946
TI  - Benefits of screening for colorectal cancer.

PMID- 9518947
TI  - SSRIs and St.John's Wort: possible toxicity?

PMID- 9518948
TI  - Pitfalls in the radiologic evaluation of extremity trauma: Part I. The upper
      extremity.
AB  - Family physicians often are required to evaluate patients who present with acute
      skeletal trauma. The first of this two-part series discusses the features and
      evaluation of some commonly missed fractures and dislocations of the upper limb,
      excluding the hand. Dislocations of the sternoclavicular joint are infrequent and
      often missed. Clavicular fractures in adults usually are not hard to diagnose.
      Acromioclavicular joint dislocations represent about 10 percent of all
      dislocation injuries to the shoulder girdle. Forty percent of all dislocations
      occur at the glenohumeral joint. Scapular fractures are often a result of
      significant force. Multiple views should be obtained in adults with a suspected
      fracture of the elbow. Complications in fractures of the wrist are strongly
      related to the location of the fracture.

PMID- 9518949
TI  - Managing the patient with hard-to-control hypertension.
AB  - Less than 25 percent of patients with hypertension in the United States have
      their blood pressure under control, mainly because of inadequate or inappropriate
      therapy and noncompliance. Approximately one half of these treatment failures are
      related to factors such as cost and adverse effects of medication, complex drug
      regimens, failure of clinicians to fully realize the benefits of antihypertensive
      therapy and lack of patient education. Other major causes of unresponsiveness to
      antihypertensive therapy include "white coat" hypertension, pseudohypertension,
      obesity, volume overload, excess alcohol intake and sleep apnea, as well as
      inappropriate antihypertensive drugs and drug combinations, and unfavorable
      interactions with prescription and other drugs. In many patients, these factors
      must be dealt with before blood pressure can be controlled.

PMID- 9518951
TI  - Examination of the placenta.
AB  - A one-minute examination of the placenta performed in the delivery room provides
      information that may be important to the care of both mother and infant. The
      findings of this assessment should be documented in the delivery records. During
      the examination, the size, shape, consistency and completeness of the placenta
      should be determined, and the presence of accessory lobes, placental infarcts,
      hemorrhage, tumors and nodules should be noted. The umbilical cord should be
      assessed for length, insertion, number of vessels, thromboses, knots and the
      presence of Wharton's jelly. The color, luster and odor of the fetal membranes
      should be evaluated, and the membranes should be examined for the presence of
      large (velamentous) vessels. Tissue may be retained because of abnormal lobation
      of the placenta or because of placenta accreta, placenta increta or placenta
      percreta. Numerous common and uncommon findings of the placenta, umbilical cord
      and membranes are associated with abnormal fetal development and perinatal
      morbidity. The placenta should be submitted for pathologic evaluation if an
      abnormality is detected or certain indications are present.

PMID- 9518952
TI  - Medical care for immigrants and refugees.
AB  - Refugees and other immigrants often present with clinical problems that are as
      varied as their previous experiences. Clinical presentations may range from
      unusual infectious diseases to problems with transition. This article describes
      medical conditions associated with immigrants, as well as specific screening
      recommendations, including history, physical examination and laboratory tests,
      and some of the challenges encountered by family physicians caring for refugees.

PMID- 9518950
TI  - Detecting celiac disease in your patients.
AB  - Celiac disease is a genetic, immunologically mediated small bowel enteropathy
      that causes malabsorption. The immune inflammatory response to gluten frequently
      causes damage to many other tissues of the body. The condition is frequently
      underdiagnosed because of its protean presentations. New prevalence data indicate
      that symptomatic and latent celiac disease is present in one of 300 people of
      European descent. Age of onset ranges from infancy to old age. Symptomatic
      presentations include general ill-health, as well as dermatologic, hematologic,
      musculoskeletal, mucosal, dental, psychologic and neurologic diseases. Celiac
      disease has a 95 percent genetic predisposition and, thus, it is frequently
      associated with autoimmune conditions such as diabetes mellitus type 1 and
      thyroid disease. Untreated patients have an increased incidence of osteoporosis
      and intestinal lymphoma. Excellent diagnostic screening tests are now available,
      including those that detect antigliadin and antiendomysial antibodies. Therapy
      with a gluten-free diet is effective, resulting in complete resolution of
      symptoms and secondary complications in almost all patients. Local and national
      celiac-sprue associations facilitate care of patients with celiac disease and
      support dietary compliance.

PMID- 9518955
TI  - Photo quiz. Common lesions on the floor of the mouth.

PMID- 9518953
TI  - Antiviral drugs in healthy children.
AB  - Several antiviral agents are available to treat viral illnesses in healthy
      children. In some children, treatment with acyclovir is an alternative to
      vaccination for the treatment and prevention of chickenpox. Acyclovir also can be
      useful in the treatment or prevention of herpes simplex infections in neonates.
      Ribavirin, once recommended as routine therapy for high-risk infants with
      respiratory syncytial virus disease, is now reserved for use in selected
      children. Amantadine and rimantidine are effective against influenza type A and
      can be used to protect children from influenza, as well as to lessen the duration
      and severity of illness in those who are already ill.

PMID- 9518954
TI  - Management of hospitalized patients with type 2 diabetes mellitus.
AB  - Subopitmal glycemic control in hospitalized patients with type 2 (non-insulin
      dependent) diabetes mellitus can have adverse consequences, including increased
      neurologic ischemia, delayed wound healing and an increased infection rate. Poor
      glycemic control can also affect the outcome of the primary illness. If possible,
      hospitalized diabetic patients should continue their previous antihyperglycemic
      treatment regimen. Decreased physical activity and the stress of illness often
      lead to hyperglycemia in hospitalized patients with type 2 diabetes. When
      indicated, insulin is given either as a supplement to usual therapy or as a
      temporary substitute. The overall benefit of the traditional sliding-scale
      insulin regimen has been questioned. Insulin supplementation given according to
      an algorithm may be a logical alternative. Any antihyperglycemic regimen should
      be administered and monitored in a manner coincident with the intake of food or
      other sources of calories. Factors that can alter glycemic control acutely,
      including specific medical conditions and medications, should be identified and
      anticipated.

PMID- 9518956
TI  - ACOG issues report on sexual assault. American College of Obstetricians and
      Gynecologists.

PMID- 9518957
TI  - IOM recommends increased calcium intakes. Institute of Medicine.

PMID- 9518958
TI  - Whatever happened to politicians' concerns about the nation's uninsured?

PMID- 9518959
TI  - Serving the medically underserved.

PMID- 9518960
TI  - Continuity of insurance coverage--a precondition for continuity of primary care.

PMID- 9518961
TI  - NORA--more than a name.

PMID- 9518962
TI  - Topics for our times: public health--community or commodity? Reflections on
      healthy communities.

PMID- 9518963
TI  - The National Occupational Research Agenda: a model of broad stakeholder input
      into priority setting.
AB  - OBJECTIVES: No single organization has the resources necessary to conduct
      occupational safety and health research to adequately serve the needs of workers
      in the United States. The National Institute for Occupational Safety and Health
      (NIOSH) undertook the task of setting research priorities in response to a
      broadly perceived need to systematically address those topics most pressing and
      most likely to yield gains to workers and to the nation. METHODS: NIOSH and its
      public and private partners used a consensus-building process to set priorities
      for the next decade for occupational safety and health research--the National
      Occupational Research Agenda. RESULTS: The process resulted in the identification
      of 21 research priorities grouped into 3 categories: disease and injury, work
      environment and workforce, and research tools and approaches. CONCLUSIONS:
      Although the field of occupational safety and health is often contentious and
      adversarial, these research priorities reflect a remarkable degree of concurrence
      among a broad range of stakeholders who provided input into a clearly defined and
      open process.

PMID- 9518964
TI  - State funding of comprehensive primary medical care service programs for
      medically underserved populations.
AB  - OBJECTIVES: This study examined the availability of state funding for
      comprehensive primary care programs and the need for primary care subsidies for
      medically underserved communities. METHODS: A brief questionnaire was used to ask
      health agencies in all 50 states whether their state funded a program that met
      our definition of comprehensive primary medical care practice programs. An in
      depth written survey instrument was then administered to the states with
      programs. RESULTS: Almost half of all states provide some funds for the
      development and/or operation of comprehensive primary medical care practices.
      Expenditures in most states were found to be relatively modest in comparison with
      both federal funding and the total level of unmet need for primary care. States
      that subsidize primary care practices tend to follow the model established under
      the federal health centers program. CONCLUSIONS: The findings suggest the
      continued viability of the health center model of care, as well as the presence
      of some state support for such a program. However, in light of limited state
      resources for the development and operation of comprehensive practices, a
      continued and significant federal effort is imperative.

PMID- 9518965
TI  - Insurance or a regular physician: which is the most powerful predictor of health
      care?
AB  - OBJECTIVES: This study compared the relative effects on access to health care of
      relationship with a regular physician and insurance status. METHODS: The subjects
      were 1952 nonretired, non-Medicare patients aged 18 to 64 years who presented
      with 1 of 6 chief complaints to 5 academic hospital emergency departments in
      Boston and Cambridge, Mass, during a 1-month study period in 1995. Access to care
      was evaluated by 3 measures: delay in seeking care for the current complaint, no
      physician visit in the previous year, and no emergency department visit in the
      previous year. RESULTS: After clinical and socioeconomic characteristics were
      controlled, lacking a regular physician was a stronger, more consistent predictor
      than insurance status of delay in seeking care (odds ratio [OR] = 1.6, 95%
      confidence interval [CI] = 1.2, 2.1), no physician visit [OR] = 4.5%, 95% CI =
      3.3, 6.1), and no emergency department visit (OR = 1.8, 95% CI = 1.4, 2.4). For
      patients with a regular physician, access was no different between the uninsured
      and the privately insured. For privately insured patients, those with no regular
      physician had worse access than those with a regular physician. CONCLUSIONS:
      Among patients presenting to emergency departments, relationship with a regular
      physician is a stronger predictor than insurance status of access to care.

PMID- 9518966
TI  - The effects of Florida's Medicaid eligibility expansion for pregnant women.
AB  - OBJECTIVES: This is a study of the effects on prenatal care and birth outcomes of
      Florida's July 1989 expansion in the Medicaid income eligibility threshold for
      pregnant women. METHODS: Concurrent and longitudinal comparisons were performed
      with matched birth and death certificates, hospital discharge data, Medicaid
      eligibility records, and records from county health departments for women giving
      birth from July 1988 to June 1989 (n = 56,101) or in calendar year 1991 (n =
      78,421). Measures included amount and timing of prenatal care and rates of low
      birthweight and infant deaths. RESULTS: The Medicaid expansion led to greater
      access and improved birth outcomes. For example, the rate of low-birthweight
      infants among low-income women without private insurance fell from 67.9 to 61.8
      per 1000, while it remained unchanged for low-income women with private
      insurance. Women in the expansion group who used county health departments had
      fewer low-birthweight infants than those using other delivery systems.
      CONCLUSIONS: The benefits from the Florida expansion appear to be greater than
      those reported for other states. The role of the public health delivery system
      may account for some of Florida's success.

PMID- 9518967
TI  - Hospital- and patient-related characteristics determining maternity length of
      stay: a hierarchical linear model approach.
AB  - OBJECTIVES: The purpose of this study was to identify factors related to
      pregnancy and childbirth that might be predictive of a patient's length of stay
      after delivery and to model variations in length of stay. METHODS: California
      hospital discharge data on maternity patients (n = 499,912) were analyzed.
      Hierarchical linear modeling was used to adjust for patient case mix and hospital
      characteristics and to account for the dependence of outcome variables within
      hospitals. RESULTS: Substantial variation in length of stay among patients was
      observed. The variation was mainly attributed to delivery type (vaginal or
      cesarean section), the patient's clinical risk factors, and severity of
      complications (if any). Furthermore, hospitals differed significantly in
      maternity lengths of stay even after adjustment for patient case mix.
      CONCLUSIONS: Developing risk-adjusted models for length of stay is a complex
      process but is essential for understanding variation. The hierarchical linear
      model approach described here represents a more efficient and appropriate way of
      studying interhospital variations than the traditional regression approach.

PMID- 9518968
TI  - Decision latitude, job strain, and myocardial infarction: a study of working men
      in Stockholm. The SHEEP Study Group. Stockholm Heart epidemiology Program.
AB  - OBJECTIVES: This study examined the role of decision latitude and job strain in
      the etiology of a first myocardial infarction. METHODS: Eligible case patients
      were all full-time working men 45 to 64 years of age who suffered a first
      myocardial infarction during the period January 1992 to January 1993 in the
      greater Stockholm region. Referents were selected from the general population.
      Participation rates were 82% (case patients) and 75% (referents). RESULTS: Both
      inferred and self-reported low decision latitude were associated with increased
      risk of a first myocardial infarction, although this association was weakened
      after adjustment for social class. A decrease in inferred decision latitude
      during the 10 years preceding the myocardial infarction was associated with
      increased risk after all adjustments, including chest pain and social class. The
      combination of high self-reported demands and low self-reported decision latitude
      was an independent predictor of risk after all adjustments. CONCLUSIONS: Both
      negative change in inferred decision latitude and self-reported job strain are
      important risk indicators in men less than 55 years of age and in blue-collar
      workers.

PMID- 9518969
TI  - Does low socioeconomic status potentiate the effects of heightened cardiovascular
      responses to stress on the progression of carotid atherosclerosis?
AB  - OBJECTIVES: This study examined whether heightened cardiovascular reactivity and
      low socioeconomic status had synergistic effects on the progression of carotid
      atherosclerosis in a population of eastern Finnish men. METHODS: Data from the
      Kuopio Ischemic Heart Disease Risk Factor Study were used to measure 4-year
      progression of intima-media thickness in 882 men according to cardiovascular
      reactivity and socioeconomic status. Associations were examined in relation to
      risk factors and were stratified by baseline levels of atherosclerosis and
      prevalent ischemic heart disease. RESULTS: The effect of reactivity on
      atherosclerotic progression depended on socioeconomic status. Men who had
      heightened cardiovascular responsiveness to stress and were born into poor
      families, received little education, or had low incomes had the greatest
      atherosclerotic progression. CONCLUSIONS: An understanding of associations
      between individual risk factors and disease should be based on etiologic
      hypotheses that are conceived at the population level and involve fundamental
      social and economic causes of disease. This study demonstrates how examining the
      interaction of an individual biological predisposition will low socioeconomic
      status over the life course is etiologically informative for understanding the
      progression of atherosclerotic vascular disease.

PMID- 9518971
TI  - Risk of ectopic pregnancy and previous induced abortion.
AB  - OBJECTIVES: This study investigated the role of prior history of induced abortion
      in subsequent ectopic pregnancies. METHODS: Data from two French case-control
      studies were used to examine the effect of induced abortion on ectopic pregnancy
      risk. Case patients (n = 570) were women admitted for ectopic pregnancy during
      the study period; controls (n = 1385) were women who delivered in the same
      center. RESULTS: The analysis among women with no previous ectopic pregnancy
      showed that, after control for the main ectopic pregnancy risk factors, prior
      induced abortion was associated with an increased risk of ectopic pregnancy (odds
      ratio [OR] = 1.5, 95% confidence interval [CI] = 1.0, 2.0); there was a
      significant trend between number of previous induced abortions and ectopic
      pregnancy risk (ORs = 1.4 for 1 previous induced abortion and 1.9 for 2 or more).
      CONCLUSIONS: This study suggests that induced abortion may be a risk factor for
      ectopic pregnancy for women with no previous ectopic pregnancy, particularly in
      the case of women who have had several induced abortions.

PMID- 9518970
TI  - Atrial fibrillation as a risk factor for stroke: a retrospective cohort study of
      hospitalized Medicare beneficiaries.
AB  - OBJECTIVES: This study examined the relationship between atrial fibrillation and
      (1) stroke and (2) all-cause mortality. METHODS: All eligible Medicare patients
      older than 65 years of age hospitalized in 1985 were followed up for 4 years.
      Kaplan-Meier and Cox proportional hazards models were used for assessment of risk
      of stroke and mortality. RESULTS: A total of 4,282,607 eligible Medicare patients
      were hospitalized in 1985. The mean age was 76.1 (+/- 7.7) years; 58.7% were
      female; 7.2% were Black; and 8.4% had a diagnosis of atrial fibrillation. During
      the follow-up period, 66,063 patients (32.6/1000 person-years) developed
      nonembolic stroke and 7285 (3.6/1000 person-years) developed embolic stroke.
      After adjustment for age, race, sex, and comorbid conditions, atrial fibrillation
      remained a significant risk factor for both nonembolic stroke (relative risk [RR]
      = 1.56) and embolic stroke (RR = 5.80) and for mortality (RR = 1.31).
      Approximately 4.5% of nonembolic and 28.7% of embolic strokes among hospitalized
      Medicare patients aged 65 years and older were attributable to atrial
      fibrillation. CONCLUSIONS: This study demonstrates that atrial fibrillation is
      associated with an appreciable increase in the risk of stroke (both embolic and
      nonembolic) and in the risk of mortality from all causes.

PMID- 9518972
TI  - Correcting for bias in relative risk estimates due to exposure measurement error:
      a case study of occupational exposure to antineoplastics in pharmacists.
AB  - OBJECTIVES: This paper describes 2 statistical methods designed to correct for
      bias from exposure measurement error in point and interval estimates of relative
      risk. METHODS: The first method takes the usual point and interval estimates of
      the log relative risk obtained from logistic regression and corrects them for
      nondifferential measurement error using an exposure measurement error model
      estimated from validation data. The second, likelihood-based method fits an
      arbitrary measurement error model suitable for the data at hand and then derives
      the model for the outcome of interest. RESULTS: Data from Valanis and colleagues'
      study of the health effects of antineoplastics exposure among hospital
      pharmacists were used to estimate the prevalence ratio of fever in the previous 3
      months from this exposure. For an interdecile increase in weekly number of drugs
      mixed, the prevalence ratio, adjusted for confounding, changed from 1.06 to 1.17
      (95% confidence interval [CI] = 1.04, 1.26) after correction for exposure
      measurement error. CONCLUSIONS: Exposure measurement error is often an important
      source of bias in public health research. Methods are available to correct such
      biases.

PMID- 9518973
TI  - How safe are our schools?
AB  - OBJECTIVES: The goal of this study was to provide national estimates of the
      frequency and cost of school injuries. METHODS: Six years of National Health
      Interview Survey data were used to estimate nonfatal injury incidence rates,
      multiple sources were used to estimate fatalities, and national highway crash
      data were used to estimate school bus injury incidence. RESULTS: Each year, 3.7
      million children suffer a substantial injury at school, resulting in an estimated
      $3.2 billion in medical spending and $115 billion in good health lost. Nonschool
      fatalities greatly exceed school fatalities; from an incidence per hour
      perspective, however, school hours are no safer than nonschool hours despite
      greater formal supervision. School bus injuries account for half of school injury
      deaths but less than 1% of total school injury costs. CONCLUSIONS: Nonfatal
      injury is a problem in schools. The concentration of injury at secondary schools
      suggests that interventions there may be most cost-effective. Data on school
      injury causes are greatly needed.

PMID- 9518974
TI  - Food insufficiency exists in the United States: results from the third National
      Health and Nutrition Examination Survey (NHANES III).
AB  - OBJECTIVES: The purpose of this study was to estimate the prevalence of food
      insufficiency in the United States and to examine sociodemographic
      characteristics related to food insufficiency. METHODS: Data were analyzed from
      the third National Health and Nutrition Examination Survey, a cross-sectional
      representative sample of the civilian noninstitutionalized population living in
      households. Individuals were classified as "food insufficient" if a family
      respondent reported that the family sometimes or often did not get enough food to
      eat. RESULTS: From 1988 through 1994, the overall prevalence of food
      insufficiency was 4.1% and was primarily related to poverty status. In the low
      income population, food insufficiency was positively associated with being
      Mexican American, being under the age of 60, having a family head who had not
      completed high school, participating in the Food Stamp Program, and not having
      health insurance. It was not related to family type or employment status of the
      family head. Over half of food-insufficient individuals lived in employed
      families. CONCLUSIONS: Food insufficiency is not limited to very low-income
      persons, specific racial/ethnic groups, family types, or the unemployed.
      Understanding food insufficiency is critical to formulating nutrition programs
      and policies.

PMID- 9518975
TI  - Promoting the selection of low-fat milk in elementary school cafeterias in an
      inner-city Latino community: evaluation of an intervention.
AB  - OBJECTIVES: This study examined the effects of a school-based intervention
      designed to promote the consumption of low-fat white milk at lunchtime in 6
      elementary schools in an inner-city, primarily Latino neighborhood. METHODS: A
      multifaceted intervention based on social marketing techniques was delivered at 3
      randomly selected schools. The school was the unit of assignment and analysis;
      6902 children were involved in the study. Milk selection and consumption were
      measured by sampling discarded milk and/or tallying milk carton disappearance at
      baseline, immediately postintervention, and at 3 to 4 months follow-up. RESULTS:
      Immediately postintervention, the mean proportion of sampled milk cartons that
      contained low-fat milk increased in the intervention schools, from 25% to 57%,
      but remained constant at 28% in the control schools. Differences between
      intervention and control schools remained significant at 3 to 4 months follow-up.
      The intervention was not associated with a decrease in overall milk consumption.
      CONCLUSIONS: A school-based intervention can lead to significant increases in
      student consumption of low-fat milk.

PMID- 9518977
TI  - Voting with their feet: public hospitals, health reform, and patient choices.
AB  - OBJECTIVES: This study identified public hospital patients' preferences under
      managed care and health reform. METHODS: A cross-sectional survey of 348
      ambulatory public hospital patients was conducted. RESULTS: Patients reported a
      high degree of loyalty to the public hospital given several hypothetical reform
      scenarios. Those patients who stated they would remain at the hospital increased
      (from 74.2% to 85.5%) when care elsewhere required copayment for medications and
      physician visits. CONCLUSIONS: Patients at one public hospital reported a high
      likelihood of remaining in the public system, and this likelihood increased when
      copayment for services was required elsewhere.

PMID- 9518976
TI  - Metropolitan governance, residential segregation, and mortality among African
      Americans.
AB  - OBJECTIVES: This study tested the hypothesis that the degree to which local
      government is metropolitanized is associated with mortality rates for African
      Americans and with residential segregation, which has itself previously been
      shown to be positively associated with mortality among African Americans.
      METHODS: One hundred fourteen US standard metropolitan statistical areas were
      examined. The primary dependent variable was the age-adjusted, race- and sex
      specific all-cause mortality rate, averaged for 1990 and 1991. The 2 primary
      independent variables were residential segregation, as measured by the index of
      dissimilarity, and metropolitanization of government, as measured by the central
      city's elasticity score. RESULTS: Mortality rates for male and female African
      Americans were lower in metropolitan statistical areas with more metropolitanized
      local governments and lower levels of residential segregation. Mortality for male
      and female Whites was not associated in either direction with residential
      segregation. White male mortality showed no association with level of
      metropolitanization, but lower White female mortality rates were associated with
      less metropolitanization. CONCLUSIONS: This study suggests the need for further
      research into whether policy changes in areas not traditionally thought of as
      "health policy" areas can improve the health of urban minorities.

PMID- 9518978
TI  - The influence of program acceptability on the effectiveness of public health
      policy: a study of directly observed therapy for tuberculosis.
AB  - OBJECTIVES: This study examined how patient acceptability influences the
      effectiveness of directly observed therapy for tuberculosis. METHODS: Decision
      and sensitivity analyses were used in assessing influences. RESULTS: If mandatory
      directly observed therapy discourages 6% of initial tuberculosis patients (range:
      4% to 10%) from seeking care, then such therapy will be less effective than self
      administered therapy. Directly observed therapy is more effective than repeated
      self-administered therapy for patients failing to complete initial treatment
      unless 32% (range: 27% to 38%) of patients avoid seeking care. CONCLUSIONS:
      Patient acceptability must be taken into consideration before selecting public
      health strategies.

PMID- 9518979
TI  - The demographic characteristics of Medicaid-eligible uninsured children.
AB  - OBJECTIVES: This study estimated the number of uninsured children in 1993 who
      were eligible for Medicaid. METHODS: Data from the March 1990 and 1994 Current
      Population Surveys were analyzed. RESULTS: At least 2.3 million Medicaid-eligible
      children were uninsured in 1993. These children were more likely to have a
      working parent than children on Medicaid. Higher proportions of uninsured
      children less than 6 years of age, children who lived in female-headed single
      parent families, and African-American and Hispanic children were eligible for
      Medicaid. CONCLUSIONS: Many eligible children do not enroll in Medicaid, and they
      differ in specific ways from enrolled children.

PMID- 9518980
TI  - The use of state and general hospitals for inpatient psychiatric care.
AB  - OBJECTIVES: This paper explores the relationship of state hospital and general
      hospital psychiatric caseloads in a statewide system of care. METHODS:
      Probabilistic population estimation was applied to general hospital and state
      hospital data sets. RESULTS: General hospitals provide inpatient psychiatric
      services to more people than do state hospitals, and a significant number are
      served in both sectors. There were notable differences in use patterns related to
      patient gender and age. CONCLUSIONS: These results demonstrate that probabilistic
      methodologies can significantly enhance the value of existing databases for
      epidemiological research.

PMID- 9518981
TI  - Health insurance coverage among Chinese Americans in Los Angeles County.
AB  - OBJECTIVES: This paper examines the factors associated with health insurance
      coverage among Chinese Americans in Los Angeles County. METHODS: Data were
      obtained through interviews conducted in 1993 and 1994 with Chinese Americans
      (aged 18 through 65 years) residing in Los Angeles County. A multistage
      probability sample was used to select respondents. RESULTS: The final sample
      consisted of 1747 respondents, which represented an 82% response rate. Thirty
      nine percent of the respondents in the survey were without health insurance at
      the time of the survey. CONCLUSIONS: Logistic regression analysis showed that
      marital status, length of residence in the United States, education, employment,
      and household income were associated with health insurance coverage among Chinese
      Americans.

PMID- 9518982
TI  - Hospital volume differences and five-year survival from breast cancer.
AB  - OBJECTIVES: The purpose of this study was to determine the effect of hospital
      volume on long-term survival for women with breast cancer. METHODS: Survival
      analysis and proportional-hazard modeling were used to assess 5-year survival and
      risk of death, adjusting for clinical and sociodemographic variables. RESULTS: At
      5 years, patients from very low-volume hospitals had a 60% greater risk of all
      cause mortality than patients from high-volume hospitals. CONCLUSIONS: Hospital
      volume of breast cancer surgical cases has a strong positive effect on 5-year
      survival. Research is needed to identify whether processes of care, especially
      postsurgical adjuvant treatments, contribute to survival differences.

PMID- 9518984
TI  - The racial segregation of hospital care revisited: Medicare discharge patterns
      and their implications.
AB  - OBJECTIVES: This paper measures current patterns of hospital segregation among
      Medicare beneficiaries. METHODS: Data from the fiscal year 1993 Medicare Provider
      Analysis and Review (MEDPAR) file, the index of dissimilarity, and a linear
      regression model are used to test the effects of standard metropolitan area
      characteristics on hospital segregation. RESULTS: The overall hospital
      segregation index was 0.529, ranging by state from 0.154 to 0.746. Hospital
      segregation in 126 standard metropolitan areas was positively related to
      population size, hospital density, and residential segregation and negatively
      related to income inequities and location in the South. CONCLUSIONS: Racial
      segregation remains high and may produce both reporting biases and unequal
      effects of public policy.

PMID- 9518983
TI  - Geographic variations in breast cancer mortality: do higher rates imply elevated
      incidence or poorer survival?
AB  - OBJECTIVES: Mortality rates from breast cancer are approximately 25% higher for
      women in the northeastern United States than for women in the South or West. This
      study examined the hypothesis that the elevation is due to decreased survival
      rather than increased incidence. METHODS: Data on breast cancer incidence,
      treatment, and mortality were reviewed. RESULTS: The elevated mortality in the
      Northeast is apparent only in older women. For women aged 65 years and older,
      breast cancer mortality is 26% higher in New England than in the South, while
      incidence is only 3% higher. Breast cancer mortality for older women by state
      correlates poorly with incidence (r = 0.28). CONCLUSIONS: Those seeking to
      explain the excess breast cancer mortality in the Northeast should assess
      survival and should examine differences in cancer control practices that affect
      survival.

PMID- 9518985
TI  - Can Medicaid managed care provide continuity of care to new Medicaid enrollees?
      An analysis of tenure on Medicaid.
AB  - OBJECTIVES: The purpose of this study was to analyze duration of coverage among
      new Medicaid enrollees. METHODS: The 1991 Survey of Income and Program
      Participation was used to examined the duration of coverage for individuals who
      did not have Medicaid in January 1991 and obtained coverage by May 1993. RESULTS:
      Of new Medicaid enrollees, 38% (90% confidence interval [CI] = 34%, 42%) remained
      covered 1 year later; 26% (90% CI = 21%, 31%) remained covered at 28 months. Of
      those older than 65 years, 54% (90% CI = 31%, 77%) retained Medicaid for 28
      months, vs 20% (90% CI = 14%, 26%) of children. Of people who lost Medicaid, 54%
      (90% CI = 31%, 77%) had no insurance the following month. CONCLUSIONS: Almost two
      thirds of new Medicaid recipients lose coverage within 12 months. It is unlikely
      that Medicaid managed care will enhance continuity of care for new recipients.

PMID- 9518986
TI  - Problem gamblers, problem substance users, and dual-problem individuals: an
      epidemiological study.
AB  - OBJECTIVES: This study compared problem gamblers, problem substance users, dual
      problem individuals, and persons without these problems in the general
      population. METHODS: On the basis of computer-assisted telephone interviews of a
      random sample of Texas adults (n = 6308) standard instruments were used to gauge
      substance use and gambling problems in the general population. RESULTS: Compared
      with those having a substance use or gambling problem only, dual-problem
      individuals were more likely to be young, never-married men, without conventional
      religious affiliations. There was more dysfunctionality (as evidenced by
      treatment-seeking and problems with the law) among dual-problem respondents than
      among those troubled exclusively by gambling or substance use problems.
      CONCLUSIONS: Screening and treatment for gambling problems should be offered in
      drug treatment and criminal justice arenas.

PMID- 9518987
TI  - Inequalities in mortality by social class measured at 3 stages of the lifecourse.
AB  - OBJECTIVES: This study examined how social class, measured at 3 staged of life,
      contributes to mortality risk. METHODS: A cohort of employed Scottish men (n =
      5567) provided their fathers' occupation and their own first and current
      occupations, from which social class in childhood, at labor-market entry, and at
      screening (1970 to 1973) was determined. Relative rates of mortality and relative
      indices of inequality were calculated from 21 years of follow-up. RESULTS:
      Mortality risk was similar at each stage of life, with men in the higher social
      classes having the lowest risk. Social class at screening produced the greatest
      relative indices of inequality. CONCLUSIONS: The widening of inequalities in
      mortality in adulthood suggests the importance of the accumulation of poor
      socioeconomic circumstances throughout life.

PMID- 9518988
TI  - Quality of reviews in epidemiology.
AB  - OBJECTIVES: This study examined the quality of recent reviews in epidemiology.
      METHODS: All 1995 issues of 7 widely read epidemiology journals were searched to
      identify reviews. RESULTS: Twenty-nine reviews were identified. Methodology was
      not specified or incomplete for literature searches in 79% of reviews; the same
      was true for inclusion criteria in 83% and for combining studies in 62%. More
      than 60% of the reviews were not methodologically systematic. CONCLUSIONS: There
      is a need to improve the quality of review papers in epidemiology. If systematic
      methodology were followed more frequently, epidemiologic science and its
      application could be improved.

PMID- 9518989
TI  - Trends in pulmonary embolism mortality in the US elderly population: 1984 through
      1991.
AB  - OBJECTIVES: This study determined race-, age- and sex-specific trends in 30-day
      pulmonary embolism mortality rates. METHODS: Medicare beneficiaries with a
      primary or secondary discharge diagnosis of pulmonary embolism from 1984 to 1991
      (n = 391,991) were examined. RESULTS: For a primary diagnosis of pulmonary
      embolism, mortality rates declined by 15.2% and 16.0%, respectively, for White
      male patients 65 to 74 years old and 75 years or older. There was a corresponding
      decline in mortality rates for White women. For a secondary diagnosis of
      pulmonary embolism, mortality rates declined by 14.7% and 9.8%, respectively, for
      White male patients 65 to 74 years old and 75 years or older. CONCLUSIONS: The
      White mortality rate declines revealed in this study did not translate, in all
      cases, to Black patient groups.

PMID- 9518992
TI  - European Journal of Vascular and Endovascular Surgery--a high quality journal.

PMID- 9518990
TI  - The effect of lead exposure on behavior problems in preschool children.
AB  - OBJECTIVES: Interpreting associations between lead exposure and child behavior
      problems is difficult because studies have not controlled for sociodemographic
      confounders or have used shed teeth to mark exposure. This study explored
      associations between blood lead and preschool behavior. METHODS: Children from a
      smelter town and a non-lead-exposed town in Yugoslavia were followed up
      prospectively from pregnancy through age 3. The Child Behavior Checklist was used
      to assess behavior problems in 379 3-year-olds, controlling for sociodemographic
      factors and difficult infant temperament. RESULTS: Multiple regression revealed
      the expected significant associations between checklist subscales and
      sociodemographic factors, which explained 7% to 18% of the variance on the
      subscales. Concurrent blood lead explained a significant 1% to 4% of the variance
      on the Destructive and Withdrawn subscales. Earlier difficult temperament
      explained an additional 2% to 5% of the checklist variance. Scores on the
      Destructive subscale were consistently associated with blood lead. As blood lead
      increased from 10 to 20 micrograms/dL, subscale scores increased by approximately
      0.5 points. CONCLUSIONS: Lead/behavior associations are significant but small
      compared with the effects of social factors.

PMID- 9518991
TI  - A regression analysis estimating the number of drug-using arrestees in 185 US
      cities.
AB  - OBJECTIVES: This study sought to provide population-based estimates of drug-using
      arrestees in the 185 largest US cities. METHODS: A prevalence model for drug
      using arrestees was developed by relating selected social indicators (from 1990
      census data) and drug use rates (from Drug Use Forecasting program data) via
      logistic regression analysis. RESULTS: It was estimated that in 1990, across the
      185 cities, about 925,000 arrestees used cocaine, 317,000 used opiates, 213,000
      used amphetamines, 389,000 were drug injectors, and 1,296,000 used an illicit
      drug. CONCLUSIONS: This approach represents a cost-efficient method for
      prevalence estimation based on empirically demonstrable relationships between
      social indicators and drug use rates.

PMID- 9518993
TI  - An introduction to quality of life analysis: the new outcome measure in vascular
      surgery.

PMID- 9518995
TI  - Venous duplex scanning for unilateral symptoms: when do we need a contralateral
      evaluation?
AB  - OBJECTIVES: Determine the need for bilateral duplex scanning (DS) in patients
      with unilateral symptoms of acute DVT of the leg. DESIGN: Prospective study.
      MATERIALS: One thousand, one hundred and sixty-one consecutive patients with
      recent unilateral symptoms of pain or swelling. METHODS: Bilateral DS were
      performed and demographic data including risk factors for DVT were entered into a
      computerised database. RESULTS: Of the 250 cases (22%) of acute DVT, thrombus was
      confined to the symptomatic limb in 80% (200/250) and to the asymptomatic limb
      (AL) in 5% (12/250), while bilateral DVT was found in 15% (38/250). The
      management was not altered by the contralateral DS findings in any patient with
      bilateral thrombus. Ten of the 12 cases of DVT confined to the AL were localised
      to the infrapopliteal level; advanced malignancy, recent joint surgery or
      hypercoagulability were noted in nine patients, including all those requiring
      treatment. CONCLUSIONS: In the presence of unilateral symptoms of DVT, we
      recommend DS of the symptomatic extremity only; bilateral examination should be
      confined to patients with normal duplex findings in the symptomatic limb
      following recent joint surgery, or in the presence of advanced malignancy or
      hypercoagulability. Bilateral DS would therefore be required in approximately 11%
      of cases with unilateral symptoms of DVT.

PMID- 9518994
TI  - The evidence for exercise-induced inflammation in intermittent claudication:
      should we encourage patients to stop walking?
AB  - OBJECTIVES: To review clinical and experimental evidence that exercise to the
      onset of calf pain in patients with intermittent claudication results in an
      inflammatory response, and to consider whether repeated inflammatory events
      induced by therapeutic exercise training may lead to progression of
      atherosclerosis. METHODS: A literature search was performed to identify studies
      measuring biochemical markers of exercise-induced ischaemia-reperfusion injury in
      patients with intermittent claudication. Current theories of atherogenesis were
      reviewed and the use of acute-phase proteins as potential markers of vascular
      disease explored. RESULTS: Exercise to the onset of calf pain results in an
      inflammatory response with free radical formation, neutrophil activation and
      systemic vascular endothelial damage. Acute-phase proteins such as C-reactive
      protein and serum amyloid A protein have exciting potential use as stable
      biochemical markers of disease in claudication. CONCLUSIONS: Further studies are
      needed to determine the effect of long-term exercise training on exercise-induced
      inflammation in claudication. Early work suggests, in fact, that exercise
      attenuates this inflammatory response. If this were confirmed then it would
      support the clinical impression that exercise training is beneficial in terms of
      symptomatic improvement and cardiovascular health in patients with intermittent
      claudication.

PMID- 9518997
TI  - A combined approach to the treatment of proximal arterial occlusions of the upper
      limb with endovascular stents.
AB  - BACKGROUND: The traditional transfemoral approach to endovascular stenting is not
      ideal for proximal arterial lesions of the upper limb. The distance of the lesion
      from the femoral puncture site, flexibility and unsupported length of guide
      wires/delivery systems and often acutely angled origins of the great vessels
      combine to make crossing the lesions and accurate deployment of the device
      difficult or impossible. Deployment of the stent via a brachial arteriotomy
      should obviate these problems. AIM: The authors report a series of patients with
      proximal arterial occlusions of the upper limb treated by endoluminal stenting
      using a combined surgical/radiological approach. PATIENTS AND METHODS: Using the
      combined approach we have attempted to treat 18 proximal upper limb occlusions
      (eight brachiocephalic origin, six subclavian origin, two subclavian artery and
      two axillary artery). Where possible, occlusions were treated by primary stent
      deployment. All patients received perioperative i.v. heparin followed by long
      term aspirin. RESULTS: Revascularisation was successful in 15 of 18 proximal
      occlusions with complete resolution of symptoms. All stented vessels remain
      patent up to 36 months after the procedure and there have been no complications
      arising from the brachial arteriotomy sites. CONCLUSIONS: Primary stenting is the
      treatment of choice for proximal occlusions of the upper limb vessels. A combined
      surgical/radiological approach via a brachial arteriotomy can be used in these
      cases and is now the method of choice for the treatment of such lesions in this
      unit.

PMID- 9518998
TI  - Exercise therapy for intermittent claudication: a review of the quality of
      randomised clinical trials and evaluation of predictive factors.
AB  - OBJECTIVE: To establish the effect of exercise therapy in patients with
      intermittent claudication and to identify outcome predictors for exercise
      training. DESIGN: A methodological study of randomised clinical trials. METHODS:
      A quality assessment of all eligible studies was performed, using a list of
      methodological criteria. A weighing scale for the criteria was developed, based
      on four main categories: study population, intervention, outcome variables and
      data presentation/analysis. RESULTS: Ten studies were included in the analysis.
      Seven randomised clinical trials had a methodological score of 60 or more points
      (maximum 100), and were considered to be of good quality. The mean of the
      methodological score was 62.5 (S.D. 8.5). Improvement in pain-free/maximum
      walking distance/time ranged from 28-210% (mean 105, S.D. 55.8). Only one study
      evaluated outcome predictors for exercise therapy. CONCLUSIONS: All studies
      reported a positive effect of exercise therapy on walking distance in patients
      with intermittent claudication, but no predictive factors were clearly
      identified. Future research efforts should focus on improving the quality of
      clinical research for patients with intermittent claudication and developing
      optimal rehabilitation programs.

PMID- 9518996
TI  - The use of tonometry to predict mortality in patients undergoing abdominal aortic
      aneurysm repair.
AB  - OBJECTIVE: To assess the reliability of intramucosal pH (pHi) of the sigmoid
      colon, IL-6 concentration and the APACHE II score in predicting outcome in
      patients undergoing elective abdominal aortic aneurysm repair. DESIGN:
      Prospective study. METHODS: In 42 patients, measurements were made of the sigmoid
      pHi with the silicone tonometer and plasma IL-6 by enzyme linked immuno-sorbent
      assay (ELISA). The daily postoperative APACHE II scores were also calculated. In
      29 patients a preoperative left ventricular ejection fraction was determined by
      gated radionuclide angiography. RESULTS: Four out of 42 patients who were studied
      died. The lowest perioperative pHi, the peak postoperative IL-6 concentration and
      APACHE II scores were significantly different in the survivors in comparison to
      the non-survivors. In the non-survivors, the fall in pHi preceded the time of
      patient's demise by at least 4 days. Significant correlations were observed
      between changes in pHi, IL-6 and APACHE II. Using receiver operating
      characteristic curves, pHi was shown to be the most predictive of mortality
      compared to the other variables. The simplicity, speed and practicality of using
      the tonometer adds to its superiority over the latter measurements. No
      relationship was found between ventricular ejection fraction, pHi and outcome.
      CONCLUSION: Although the number of patients is small, these results support pHi
      as a valuable predictor of outcome and also suggest a role for the gut in
      initiating the IL-6 and physiological responses.

PMID- 9519000
TI  - Early results of percutaneous transluminal angioplasty (PTA) of failing below
      knee bypass grafts.
AB  - OBJECTIVES: An audit of treating femoro-crural bypass stenosis in the first
      instance by PTA. DESIGN: Prospective clinical pilot study in consecutive
      patients. MATERIALS: Prior to vascular bypass grafting all patients had critical
      ischaemia. Sixty-four PTA procedures in 50 grafts in 49 patients were carried
      out. Thirteen were in situ saphenous grafts, 16 were combined venous segments, 18
      were combined PTFE and vein and three were PTFE only. METHODS: Conventional cross
      over or antegrade PTA, eventually combined with local thrombolytic therapy.
      RESULTS: The nine-month assisted patency using PTA was 72%, following surgical
      repair in five cases after failed PTA the secondary patency was 86%. The
      amputation free survival rate was 88%. In 11 cases thrombosis was treated
      successfully with local thrombolysis. In two cases the balloon ruptured the
      native artery wall below the distal anastomosis with pseudoaneurysm formation.
      Six limbs were amputated during follow-up. The frequency of stenosis in combined
      grafts was significantly higher than in in situ vein grafts. CONCLUSION: Our
      results are comparable with surgery. About 600 hospital beds/days were saved.
      This shortened the time from the diagnosis of stenosis to therapy and shortened
      the waiting list for vascular surgery.

PMID- 9518999
TI  - A comparison between colour duplex ultrasonography and arteriography for imaging
      infrapopliteal arterial lesions.
AB  - OBJECTIVE: To investigate the agreement between colour duplex ultrasonography and
      digital subtraction arteriography of the infrapopliteal arteries. DESIGN:
      Retrospective, blinded study. SETTING: Vascular laboratory and Radiology
      Department, University Hospital. METHODS: The infrapopliteal vasculature was
      examined in a total of 51 limbs by both colour duplex ultrasound and digital
      subtraction angiography. By examining all arteries from the distal popliteal to
      the pedal arteries, a total of 204 individual arterial segments were available
      for analysis. Each segment was graded as 0-49%, 50-99% diameter reduced or
      occluded by both modalities. Using ultrasound, classification of stenoses was
      achieved by observing peak systolic velocity ratios; a doubling of peak systolic
      velocity indicating a > or = 50% diameter reducing stenosis. Where no Doppler
      signal could be obtained, the vessel was assumed to be occluded. From
      angiographic studies, two radiologists separately and blindly assessed the extent
      of disease for each infrapopliteal artery noting areas of > or = 50% diameter
      reduction and occlusion. The Kappa statistic was used to examine the level of
      agreement between angiography and ultrasound as well as between both
      radiologists. RESULTS: The Kappa level (95% confidence interval) of agreement
      between ultrasound and angiographic assessments for distinguishing patent from
      occluded segments was 0.61 (0.49-0.74) for all segments. The equivalent agreement
      between radiologists was 0.80 (0.70-0.89). Poorest agreement was observed from
      ultrasound assessments of the peroneal and tibioperoneal trunk arterial segments.
      CONCLUSION: Since agreement between colour duplex scanning and angiography never
      fell significantly below levels achieved between two radiologists, we conclude
      that colour duplex ultrasound can be used to assess infrapopliteal artery
      patency.

PMID- 9519001
TI  - Discrepancy between stent deployment and balloon size used assessed by
      intravascular ultrasound.
AB  - OBJECTIVES: This study was designed to assess the discrepancy in stent deployment
      seen on intravascular ultrasound and its relation to the balloon size selected
      for stent delivery. DESIGN: Prospective study. MATERIALS AND METHODS: The study
      group comprised 27 patients treated using a stent (n = 18) or stent-graft
      combination (n = 9). Following angiographically optimal stent deployment (< 10%
      residual stenosis) intravascular ultrasound was used to compare the smallest
      intra-stent lumen area with measurements at both stent edges and the lumen area
      of the proximal and distal reference sites. RESULTS: In 14 of the 27 stents the
      intra-stent dimension was the same as the dimension of the stent edge (difference
      < or = +/- 10%). Of the remaining stents the intra-stent dimension was smaller
      (difference > 10%) than the proximal stent edge in seven stents (range 11-39%),
      smaller than the distal stent edge in three stents (range 11-20%) and smaller
      than both stent edges in three stents (range 12-37%). Both in patients treated
      with a stent or stent-graft combination, the resulting smallest intra-stent lumen
      area was smaller than the balloon size used (mean difference 32% and 42%,
      respectively) and smaller than the mean lumen area of the reference sites (mean
      difference 25% and 23%, respectively). CONCLUSION: This intravascular ultrasound
      study shows a discrepancy between intra-stent lumen area, the area of the stent
      edges and the balloon size used.

PMID- 9519002
TI  - Ruptured abdominal aortic aneurysms: factors influencing postoperative mortality
      and long-term survival.
AB  - OBJECTIVE: To update mortality rates and long-term survival of patients admitted
      to the hospital with ruptured abdominal aortic aneurysm (AAA) and to study
      prognostic factors associated with mortality. DESIGN: Retrospective follow-up.
      MATERIALS: 309 patients (274 men, 35 women, average age 71) admitted to the
      hospital between January 1980 and January 1994 who were surgically treated for
      ruptured AAA were studied. METHODS: To identify the preoperative (9),
      intraoperative (23) and postoperative (49) variables associated with mortality
      logistic regression analysis (mortality within 48 h) and Cox regression analysis
      (mortality between 48 h and 30 days) were performed. RESULTS: Hospital mortality
      improved from 1980 to 1994. Compared with the normal population adjusted for age
      and sex the long-term mortality rate was increased (standardised mortality ratio
      2.1; 95% confidence interval 1.7-2.5). Increased age, peroperative hypotension
      and need for a bifurcated graft were associated with significantly increased
      mortality. Co-morbidity was not a predictive variable. Overall hospital mortality
      was 25%. CONCLUSION: Surgical repair of ruptured AAA should be considered even in
      patients with co-morbidity. Elderly patients with severe preoperative hypotension
      have a very high mortality rate and surgery may not be justified in these cases.
      Long-term survival is also worse in older patients.

PMID- 9519004
TI  - Continuous monitoring of intrathecal pO2, pCO2 and pH during surgical replacement
      of type II thoracoabdominal aortic aneurysm.

PMID- 9519003
TI  - Early haemodynamic changes in the ophthalmic artery, siphon and intracranial
      arteries after carotid endarterectomy estimated by transcranial Doppler and
      duplex scanning.
AB  - OBJECTIVES: To study early haemodynamic changes in connection with carotid
      endarterectomy (CE). METHODS: Sixty-three consecutive patients, average age 64,
      with symptomatic stenosis in the internal carotid artery (ICA) > or = 70% were
      examined clinically and by transcranial Doppler (TCD) 1 day before and within 48
      h after CE. Duplex scanning of extracranial vessels was performed within 1 week
      after CE. RESULTS: After CE, all retrograde systolic velocities (SV) in the
      ophthalmic artery (OA) and 9/10 retrograde mean velocities (MV) in the siphon
      changed to antegrade. Antegrade SV in the OA increased significantly (p < 0.001)
      only on the operated side. SV in the OA on the operated side correlated (p <
      0.05) with MV in the siphon, and pulsatility index (PI) in the middle cerebral
      artery (MCA, p < 0.001). MV in the MCA increased from 46 +/- 12 cm/s to 59 +/- 21
      cm/s after CE and in the ACA with normal flow from 54 +/- 19 cm/s to 62 +/- 28
      cm/s (p < 0.001 and < 0.05, respectively) only on the operated side. Stump
      pressure correlated (p < 0.01) with SV in the OA and PI in the MCA and was higher
      (59 +/- 16 mmHg, p < 0.01) in the group with antegrade flow in the OA compared to
      the group with retrograde flow in the OA (43 +/- 15 mmHg). CONCLUSION: TCD and
      duplex gives important early information about patency of the ICA and
      haemodynamic intracranial changes after CE.

PMID- 9519005
TI  - A simple technique to assist in the repair of thoracoabdominal aneurysms.

PMID- 9519006
TI  - Aortovenous fistula to the inferior mesenteric vein in a ruptured abdominal
      aortic aneurysm.

PMID- 9519007
TI  - Widespread arterial thrombosis in association with metastatic carcinoma--a case
      report.

PMID- 9519008
TI  - Helping patients quit smoking.

PMID- 9519009
TI  - Amiodarone and mortality in CHF and post-MI.

PMID- 9519010
TI  - Information leaflet for lower respiratory illness.

PMID- 9519011
TI  - Anesthesia and neonatal circumcision.

PMID- 9519012
TI  - PPIs vs H2RAs for erosive reflux esophagitis.

PMID- 9519013
TI  - Evaluation of chest pain using cardiac troponins T and I.

PMID- 9519014
TI  - Gowning and patient satisfaction.

PMID- 9519015
TI  - Speed of anticoagulation in DVT.

PMID- 9519016
TI  - The AAFP research initiative.

PMID- 9519017
TI  - From blame to understanding: moving diabetes care forward.

PMID- 9519018
TI  - How patients adapt diabetes self-care recommendations in everyday life.
AB  - BACKGROUND: Our study explored behavioral factors affecting what patients with
      type 2 diabetes do for self-care and why they do it. The findings were used to
      develop clinical recommendations to improve intervention strategies. METHODS:
      Interviewers, using open-ended questions, explored patients' own perceptions and
      assessments of self-care behaviors. The fifty-one subjects were self-identified
      Mexican Americans who had type 2 diabetes for at least 6 months, and had no major
      impairment as a result of this diabetes. Texts of patient interviews were
      analyzed by building and refining matrixes to display and compare central themes
      regarding treatment strategies and their contexts. RESULTS: All patients were
      trying to control their diabetes, but none of them followed recommendations
      completely. Instead, they adapted self-care behaviors to the exigencies of
      everyday life. Key factors influencing patients' treatment choices were: (1) the
      belief in the power of modern medicine; (2) the desire to act and feel "normal";
      (3) the desire to avoid physical symptoms; and (4) limited economic resources.
      CONCLUSIONS: As patients apply treatment recommendations in the context of their
      everyday lives, they continually must make many small decisions affecting self
      care behavior. The specific contexts of patients' lives, including their
      economic, educational, and cultural circumstances, determine how the generalized
      principles of type 2 diabetes management are implemented. Clinical strategies
      must be responsive to these circumstances in order to enable patients to make
      appropriate decisions when adapting their self-care behaviors to their own
      situations.

PMID- 9519019
TI  - Consumer experiences and provider perceptions of the quality of primary care:
      implications for managed care.
AB  - BACKGROUND: The purpose of this study was to determine the extent to which
      consumer and provider reports of primary care differ according to particular
      characteristics of the primary care setting. METHODS: A random sample of
      consumers was surveyed by telephone in a defined geographic area of Washington,
      DC, to determine their experiences with care provided to a randomly chosen child.
      The primary care provider of each respondent was sent a parallel survey. Scores
      were obtained for each of two subdomains in the four cardinal primary care
      domains (first contact, longitudinality, comprehensiveness, and coordination) and
      for three related domains (family centeredness, community orientation, and
      cultural competence). Differences between settings that did or did not impose
      limitations on autonomy for referrals and between fee-for-service and capitated
      settings were ascertained. RESULTS: Both consumers and their providers in
      settings characterized by high degrees of limitation on physician autonomy or by
      capitation reported better first-contact accessibility and a greater range of
      services available than did consumers in settings with low degrees of limitation,
      or by fee-for-service reimbursements to physicians. Consumers but not providers
      reported better family centeredness in these settings. Most other differences
      favored these settings as well, but these were not consistently statistically
      significant for both providers and consumers in both types of settings.
      CONCLUSIONS: The quality of primary care services in different settings can be
      ascertained by using an instrument with demonstrated reliability and convergent
      validity. Although certain types of settings, in the particular geographic area
      studied, appear to perform better in several key aspects of the primary care,
      replication of the study in other areas would be useful judging the performance
      of the newer types of settings to be superior to more conventional care for
      general populations.

PMID- 9519020
TI  - How concerned are elderly patients without coronary heart disease about
      hypercholesterolemia and heart disease? An UPRNet study. Upper Peninsula Research
      Network.
AB  - BACKGROUND: There has been much controversy in the medical literature regarding
      the benefit of treating elevated cholesterol levels in asymptomatic elderly
      people (65 years of age and older) to prevent coronary heart disease (CHD).
      Little has been published about the attitudes and beliefs of elderly patients
      regarding the importance of cholesterol levels to their health. This study seeks
      to describe the importance that elderly persons place on cholesterol in regard to
      heart disease, how worried they are about it, and what behavior changes they are
      making to control their own cholesterol levels. METHODS: We used a cross
      sectional questionnaire to study elderly primary care patients in a rural setting
      with no personal history of coronary heart disease. RESULTS: Six hundred eighty
      patient questionnaires were analyzed. Ninety-six percent of respondents believed
      high cholesterol to be at least moderately important for heart disease; 67%
      believed it to be very important. Fifty-nine percent were at least slightly
      worried about their own cholesterol level. Seventy-four percent said they had had
      their cholesterol checked within the past 2 years, and 66% had discussed their
      cholesterol level with their physician within the past 2 years. Sixty-six percent
      were trying to keep their cholesterol level down by dieting (42%), exercising
      (39%), or taking prescription medicine (15%). CONCLUSIONS: Elderly patients who
      responded to this questionnaire are aware that hypercholesterolemia is a risk
      factor for CHD, and many eat a low-fat diet, exercise, or take prescription
      medication to lower their cholesterol. Physicians should be aware that many
      elderly patients without an established diagnosis of CHD are concerned about
      their cholesterol level. Physicians should be prepared to discuss with their
      elderly patients the potential advantages and disadvantages of the treatment of
      asymptomatic hypercholesterolemia.

PMID- 9519021
TI  - The determination and interpretation of reference intervals for multichannel
      serum chemistry tests.
AB  - BACKGROUND: When interpreting the results of clinical chemistry tests, physicians
      rely heavily on the reference intervals provided by the laboratory. It is assumed
      that these reference intervals are calculated from the results of tests done on
      healthy individuals, and, except when noted, apply to people of both genders and
      any age, race, or body build. While analyzing data from a large screening
      project, we had reason to question these assumptions. METHODS: The results of 20
      serum chemistry tests performed on 8818 members of a state health insurance plan
      were analyzed. Subgroups were defined according to age, race, sex, and body mass
      index. A very healthy subgroup (n = 270) was also defined using a written
      questionnaire and the Duke Health Profile. Reference intervals for the results of
      each test calculated from the entire group and each subgroup were compared with
      those recommended by the laboratory that performed the tests and with each other.
      Telephone calls were made to four different clinical laboratories to determine
      how reference intervals are set, and standard recommendations and the relevant
      literature were reviewed. RESULTS: The results from our study population differed
      significantly from laboratory recommendations on 29 of the 39 reference limits
      examined, at least seven of which appeared to be clinically important. In the
      subpopulation comparisons, "healthy" compared with everyone else, old (> or = 75
      years) compared with young, high (> or = 27.1) compared with low body mass index
      (BMI), and white compared with nonwhite, 2, 11, 10, and 0 limits differed,
      respectively. None of the contacted laboratories were following published
      recommendations for setting reference intervals for clinical chemistries. The
      methods used by the laboratories included acceptance of the intervals recommended
      by manufacturers of test equipment, analyses of all test results from the
      laboratory over time, and testing of employee volunteers. CONCLUSIONS: Physicians
      should recognize when interpreting serum chemistry test results that the
      reference intervals provided may not have been determined properly. Clinical
      laboratories should more closely follow standard guidelines when setting
      reference intervals and provide more information to physicians regarding the
      population used to set them. Efforts should be made to provide appropriate
      intervals for patients of different body mass index and age.

PMID- 9519023
TI  - Traumatic arteriovenous fistula of the leg. An easily missed diagnosis.
AB  - An arteriovenous fistula is an abnormal communication between the arterial and
      venous systems. It may be an incidental finding in an asymptomatic patient or it
      may manifest clinically with pain, edema, varicosities, and even heart failure.
      It is important for clinicians to be aware of this disorder because early
      diagnosis and treatment can prevent its long-term sequelae. This report presents
      a patient with a posttraumatic arteriovenous fistula.

PMID- 9519022
TI  - Ineffectiveness of topical benzocaine spray during colposcopy.
AB  - BACKGROUND: Colposcopic evaluation can cause patients to experience pain and
      anxiety. This study investigated the use of benzocaine spray, a topical
      anesthetic, and its effects on pain and anxiety associated with colposcopy and
      colposcopic biopsy. METHODS: The study was a double-blind, placebo-controlled
      trial of the effectiveness of benzocaine spray applied to the cervix immediately
      before colposcopic examination, cervical biopsy, or endocervical curettage in
      patients of a family practice center. Prior to the gynecologic procedure the
      patient's cervix was sprayed with either benzocaine spray or matching placebo
      spray. After waiting at least 30 seconds the clinician started the procedure.
      Pain and anxiety, measured on 10-cm visual analog scales, were determined at the
      following times: (1) before the start of the gynecologic examination; (2)
      immediately before using the spray; (3) immediately after using the spray; and,
      (4) after the procedure was completed. RESULTS: Of 58 consecutive patients who
      underwent colposcopy, 36 patients were eligible for the trial and were evaluated.
      Participants were similar to patients not participating with regard to race,
      gravidity, and parity. Statistical analysis found significant differences in both
      pain and anxiety scores over time (repeated measures multivariate ANOVA, P <
      .0001), but no difference between the use of active drug and placebo. Pain scores
      increased significantly after application of either benzocaine or placebo spray
      before the start of the procedure (average increase 1.3 cm, P < .0001).
      CONCLUSIONS: Benzocaine, in a spray vehicle, confers no benefit when used to
      decrease pain and anxiety in women undergoing colposcopic procedures.

PMID- 9519024
TI  - Legal implications of birth videos.
AB  - There is little information available in the peer-reviewed literature on the
      medical and legal aspects of videotaping obstetric procedures. To manage legal
      risks, some large medical centers do not allow families to videotape the birth.
      One liability insurer is now attempting to limit video cameras in labor and
      delivery suites throughout its state. These policies can have significant
      implications for physicians and their patients. In an effort to examine
      approaches to the problem, we gathered the experiences of physician and attorney
      members of the American College of Legal Medicine through letters and telephone
      conversations, and we performed a review of the available medical and legal
      literature. Based on this research and review, we present the benefits and risks
      of permitting families to videotape the birth process, and we make
      recommendations for reducing potential liability.

PMID- 9519025
TI  - The benefits of gatekeeping.

PMID- 9519026
TI  - Office BP measurements.

PMID- 9519027
TI  - Alternative pharmacotherapy.

PMID- 9519028
TI  - MedWatch: FDA's Medical Products Reporting Program.

PMID- 9519029
TI  - When the face tells the tale. Course facial features caused by phenytoin use.

PMID- 9519030
TI  - Asthma management. The case for aiming at control rather than merely relief.
AB  - Asthma is a common and eminently treatable disease. Most asthma patients are
      initially seen by primary care physicians, who are likely to have a significant
      part in management. Research has provided physicians with a better understanding
      of the pathophysiologic basis of asthma and new antiasthma agents. Guidelines
      have been published to disseminate asthma management information. On the basis of
      these advances, there appears to be no reason that informed physicians cannot
      play an important role in reversing recent trends of rising asthma morbidity and
      mortality.

PMID- 9519031
TI  - Coronary artery disease in women. How customary expectations can interfere with
      interpretation of test results.
AB  - Although one in three women in the United States will die of heart disease,
      traditionally coronary artery disease (CAD) in women has received less
      recognition as a public health problem than has the disease in men. To assist
      practicing physicians in recognizing CAD in women, this article reviews sex
      differences in risk factors and manifestations of CAD as well as strengths and
      weaknesses of various diagnostic tests in women.

PMID- 9519032
TI  - Streptokinase therapy. Recognizing and treating allergic reactions.
AB  - Streptokinase is an important component in the treatment strategy for acute
      myocardial infarction. However, physicians need to be aware that some patients
      may experience allergic reactions to this drug. Prompt recognition and
      appropriate management of symptoms usually result in recovery from the allergic
      event without further complication.

PMID- 9519033
TI  - Bacterial meningitis in children and adults. Changes in community-acquired
      disease may affect patient care.
AB  - Despite improved understanding of how bacterial meningitis develops, the
      infection remains a potentially life-threatening emergency capable of causing
      significant morbidity and mortality. Since the introduction and widespread use of
      H influenzae type b vaccine in infancy and childhood in North America, the
      epidemiology of community-acquired bacterial meningitis has changed. S pneumoniae
      is now the most common cause in children and adults overall, although N
      meningitidis causes most disease in patients between ages 2 and 18 years. Broad
      spectrum cephalosporins (eg, ceftriaxone, cefotaxime) are considered the agents
      of choice for empirical treatment of bacterial meningitis. However, use of these
      agents will have to be reconsidered if the incidence of invasive infection from
      drug-resistant S pneumoniae continues to increase. The role of adjunctive
      corticosteroid therapy needs to be better defined. Improved conjugate
      pneumococcal and meningococcal vaccines may soon make bacterial meningitis a
      preventable disease.

PMID- 9519034
TI  - Encephalitis. Identifying the specific cause is key to effective management.
AB  - Acute viral encephalitis and postinfectious encephalomyelitis affect both
      children and adults. Enteroviruses, HSV types 1 and 2, and arboviruses are the
      most common causes of encephalitis in the United States; however, the
      differential diagnosis is broad. History taking and physical examination can
      provide clues to the cause, but the diagnosis is usually established on the basis
      of CSF analysis, viral culture, MRI, and serologic testing, when indicated. In
      the future, PCR techniques may enhance rapidity of diagnosis. Until the specific
      cause is identified, empirical therapy should be given. Because complications can
      be severe, all patients with encephalitis should be monitored in a facility
      capable of providing supportive intensive care. Long-term follow-up is important
      to detect sequelae, particularly in patients with eastern equine or HSV
      encephalitis.

PMID- 9519035
TI  - Neurologic manifestations of HIV infection. Using imaging studies and antiviral
      therapy effectively.
AB  - Patients with HIV infection are at risk for neurologic complications that can
      arise through various means. Nervous system disorders sometimes occur as a direct
      consequence of the HIV infection itself. Or, as immunodeficiency progresses,
      patients can become susceptible to numerous opportunistic infections and other
      conditions that have neurologic involvement. Even the antiviral drugs used to
      treat HIV infection can induce neurologic manifestations. Dr Rachlis discusses
      several of these manifestations and their management.

PMID- 9519037
TI  - Biopsy of the skin. Thoughtful selection of technique improves yield.
AB  - Skin biopsy can serve both diagnostic and therapeutic purposes. Site selection is
      not of major importance in the many types of lesions suggestive of malignancy but
      is crucial with diffuse eruptions. The shave technique is appropriate for many
      neoplastic lesions, while punch or incisional/excisional biopsy is necessary for
      more deeply invasive lesions. A variety of anesthetics are available to aid in
      patient comfort, as are a number of techniques for accomplishing the procedure to
      achieve the best cosmetic result.

PMID- 9519036
TI  - Depression in community-dwelling elders. Overcoming treatment obstacles with new
      antidepressants.
AB  - Although depression is the most common psychiatric disorder among older adults,
      it continues to be misdiagnosed and undertreated in this population for a variety
      of reasons. The authors present an overview of the efficacy and side effects of
      antidepressant medications, pointing out advantages of new drugs that are
      especially important in older patients.

PMID- 9519038
TI  - Otitis media in children. Diagnosis, Treatment, and Prevention. Institute for
      Clinical Systems Integration.

PMID- 9519039
TI  - Monitoring blood levels of selected drugs. Remember to factor in the many
      confounding variables.
AB  - Appropriate use of various pharmacologic agents involves not only awareness of
      therapeutic indications and side effects but also familiarity with clinical use
      and timing of blood level monitoring. The effective as well as the toxic level of
      antiepileptic drugs varies widely among patients, so the patient's response is
      more important than the serum drug level. These agents may interact with other
      disease states, other drugs, and even other antiepileptic agents. Because of
      digoxin's long half-life and the effect of physical exercise on serum
      concentration, the timing of serum collection is important. The usefulness of
      measuring amiodarone serum concentrations is controversial, but findings may help
      identify patients at risk for side effects related to the drug. Procainamide has
      a very short half-life and concentrations change over a short period, so blood
      levels of this agent should be measured before administration of a dose. The dose
      of levothyroxine required to restore a normal thyroid hormone level varies with
      age, coexistent conditions, and use of other medications. After the appropriate
      dose is determined, follow-up monitoring yearly is necessary (more often in the
      elderly). Efficacy and toxicity of theophylline are directly related to serum
      concentrations, and a reduced target level of 5 to 15 micrograms/mL has recently
      been suggested. Proper monitoring is important, because metabolic changes and
      drug interactions can cause either subtherapeutic or toxic levels.

PMID- 9519040
TI  - Helicobacter pylori and peptic ulcer disease. Bridging the gap between knowledge
      and treatment.
AB  - Eradication of H pylori and cure of peptic ulcer disease are possible if
      effective regimens are used correctly. Treatment markedly improves clinical
      outcomes and significantly decreases cost of care. As primary care physicians
      take a larger role in management of these infections, they need to understand the
      importance of identifying and treating patients with H pylori-associated peptic
      ulcer disease. Successful treatment of this infection depends on the appropriate
      antimicrobial therapy and patient compliance with the chosen regimen.

PMID- 9519041
TI  - Comprehensive geriatric assessment. Helping your elderly patients maintain
      functional well-being.
AB  - In this article, three geriatricians describe an approach to comprehensive
      geriatric assessment that takes into account the multiple social and medical
      problems that affect the functional well-being of frail elderly patients. With a
      45- to 90-minute time investment, physicians can obtain an inventory of the
      factors that threaten an elderly patient's independence and gain a fuller
      understanding of the patient's complex needs.

PMID- 9519042
TI  - [Chronic recurrent multifocal osteomyelitis (CRMO)].
AB  - Chronic recurrent multifocal osteomyelitis (CRMO) is an unusual clinical entity.
      More than 200 cases are described in the literature and it is presented here with
      special reference to its radiological aspects. It is an acquired disease of the
      skeleton which occurs predominantly during childhood and adolescence. About ten
      per cent of cases begin in early or, rarely, in later adult life. This variant is
      described here for the first time and is discussed as "adult CRMO". The
      underlying pathology is a bland, predominantly lympho-plasma cellular
      osteomyelitis which is self-limiting and leads to bone sclerosis (Garre). It
      probably involves an abnormal immune process which follows an infection but
      remains clinically latent and remains aseptic and sterile. In a quarter of cases
      there is an association with pustulosis palmo-plantaris and its relationship with
      psoriatic arthropathy is discussed. The clinical, histopathological and imaging
      features (radiological and particularly MRT) and the bone changes are described.
      This provides a spectrum of symptoms; the radiological differential diagnosis and
      the relationship with hyperostotic spondyloarthroses during adult life are
      discussed. The relationship between CRMO, the SAPHO syndrome and acquired
      hyperostosis syndrome are analysed.

PMID- 9519043
TI  - [Osteoclastic finger arthrosis--a subtype of hand polyarthrosis].
AB  - AIM: Description of a subtype of arthrosis deformans of the hand which is
      characterised as osteoclastic arthrosis. PATIENTS AND METHODS: Retrospective
      analysis of radiographs of the hands of 150 women and 100 men with radiological
      findings of arthrosis deformans. RESULTS: 5% of women and 2% of men showed at
      least one digital joint with subchondral osteolysis of one or both articulating
      bones involving at least a third of the phalanx. This subchondral osteolysis far
      exceeds the cysts which are situated in the epiphyseal part of the articular
      region. It may develop within a year. CONCLUSION: Osteoclastic arthrosis of the
      finger is a subtype of polyarthrosis of the hand. Serial observations suggest
      that an osteoclast stimulating substance is produced by the cysts or arises
      directly from the synovial fluid; this enters the subchondral part of the bone
      through clefts which may or may not be visible radiologically and that this
      produces osteoclastic activity. The most important differential diagnoses are
      chronic tophaceous gout and a benign tumor.

PMID- 9519044
TI  - [A new specimen radiography device with a maximum 20-fold magnification for
      breast diagnosis].
AB  - PURPOSE: A radiography system specially developed for specimen radiography and
      allowing maximal 20-fold magnification is presented. The efficiency of the system
      was tested and compared with that of conventional magnification mammography
      systems. METHODS: 23 surgical and 90 core biopsies of the breast were examined
      for detection of microcalcifications. As criteria the number of identifiable
      calcifications, their shape and configuration as well as tissue contrast were
      chosen. RESULTS: The new technique detected about 400% more microcalcifications,
      200% more core and 50% more surgical biopsies containing calcifications. Thus, in
      a few cases, additional core biopsies were unnecessary. Moreover, this new system
      yielded additional information for the pathologist and surgeon concerning the
      exact localisation of suspicious lesions that facilitated working up specimens,
      or indicated additional surgical removal in special cases. CONCLUSIONS: By
      identification of malignant lesions not detectable with conventional
      magnification radiography systems, as well as a more exact localisation of
      suspicious lesions, false negative results may be reduced.

PMID- 9519045
TI  - [Window width as a dosage-relevant factor in high-contrast structures in CT].
AB  - PURPOSE: To establish the relationship between window width and dose to be
      applied in low-dose high-resolution (HR) computed tomography (CT). MATERIAL AND
      METHODS: Low-dose HR CT-scans of the petrous bone displayed with different window
      values were analyzed for identification of osseous details. For two homogeneous
      phantoms, standard deviation of CT-numbers were measured in order to calculate
      the fraction of pixels not displayed within the correct grey level. RESULTS: The
      broadest window used (4000 HU) allowed the best distinction of osseous
      structures. Standard deviation of CT-numbers in the phantoms varied between 28.5
      and 43.2 (mean = 33.6) HU. Thus, only 26.6% of all pixels are displayed in the
      correct grey level for a 1000 HU-window, but 82.3% for a 4000 HU-window.
      CONCLUSION: When using low doses and HR-reconstruction algorithms, large window
      widths allow for an optimal assessment of high-contrast structures. Under these
      conditions, even high standard deviations of the CT-numbers will not compromise
      image evaluation. Due to the restricted number of grey-levels that can be
      distinguished by the human eye, image noise is compressed into a smaller number
      of discernable grey-levels. Because of the inverse square root function between
      dose to be applied and window width used (derived in the article), an even minor
      enlargement of window permits considerable reductions of patient exposure while
      the discernable image noise remains constant.

PMID- 9519046
TI  - [The assessment of the morphological changes after ventral diskectomy by thin
      section computed tomography].
AB  - PURPOSE: We examined the changes of the intervertebral body space, the morphology
      of bone cement interponates and vertebrae after cervical discectomy and ventral
      fusion with high resolution CT. MATERIALS AND METHODS: CT scans were performed on
      25 patients preoperatively, one week and six months after cervical discectomy and
      ventral fusion. RESULTS: There was no change in the size of the interponates.
      During follow-up new ossifications were found in 18 of the patients, two of them
      with neurological deficits. While directly after surgery the sagittal spinal
      canal diameter was enlarged, six months later particularly the lateral width was
      found to be reduced. After surgery soft tissue already narrowed the spinal canal
      in similar shape as the former prolapse. CONCLUSION: We conclude that
      postoperative neurologic deficits can only be partially explained by the
      described structural changes, because similar findings were made in uncomplicated
      postoperative courses as well as in patients with deficits.

PMID- 9519047
TI  - [The diagnostic accuracy and therapeutic relevance of CT arthrography and MR
      arthrography of the shoulder].
AB  - PURPOSE: In glenohumeral instability, CT arthrography and MR arthrography of the
      shoulder joint were compared to assess accuracy in diagnosis of labral lesions
      and other internal derangements of the joint, and to evaluate relevance of both
      imaging methods for therapy. METHODS: 38 patients with symptoms of shoulder
      instability were examined clinically, arthrographically with CT and MRI, and
      arthroscopically. Arthrography with CT and MRI was performed in a double-contrast
      technique after single puncture and simultaneous injection of the contrast agents
      for both imaging methods. Type and extent of lesions on arthrographic imaging
      were criteria for planning therapy to a conservative, sole arthroscopic, or open
      surgical approach. RESULTS: Sensitivity in diagnosis of labral lesion (26
      defects) was 85% in CT, 88% in MRI and 100% if both methods were used. Full
      thickness tears of the rotator cuff were visualised in CT in 73%, and in MRI in
      100%. Diagnostic accuracy increased from partial to complete to total defects. An
      open surgical approach was correctly predicted on MRI in 90% and on CT in 71%. A
      sole arthroscopic therapy was correctly foreseen on both arthrographic techniques
      in only 38% due to difficulties to assess glenohumeral ligaments. CONCLUSIONS: CT
      arthrography and MR arthrography were excellent for diagnosing labral lesions.
      MRI is superior to CT in the imaging of all joint structures. Surgical approach
      can be accurately predicted with both imaging methods but special surgical
      techniques cannot be effectively planned to replace diagnostic arthroscopy in all
      cases.

PMID- 9519049
TI  - [The staging of renal-cell carcinomas in MRT and CT--a prospective histologically
      controlled study].
AB  - PURPOSE: To evaluate the accuracy of computed tomography (CT) and magnetic
      resonance imaging (MRI) in staging renal carcinoma. MATERIAL AND METHODS: 33
      renal carcinomas were preoperatively examined for tumour staging by CT and MR
      imaging and correlated with histopathological staging. CT imaging was performed
      at first as a non-contrast scan. Finally incremental images (10 mm) after
      intravenous contrast injection were obtained. In MR imaging we performed a
      transversal T1-weighted GE sequence (112/5) with and without GDTPA, a transversal
      fat-suppressed double-echo sequence (3900/22/90), a coronal T1-weighted GE
      sequence with and without GDTPA and a coronal T2-weighted TSE sequence
      (2800/128). In addition, dynamic T1-weighted GE imaging after GDTPA injection as
      well as TOF angiography in coronal direction were performed. Finally CT and MRI
      findings were correlated with surgical and histopathological staging results.
      RESULTS: CT and MRI staging was correct in 27 and 28 of 33 tumours. Sensitivity
      and specificity for tumour stage T3b to T4 was for MRI and CT 88.9% and 95.8%.
      With MRI 4 out of 7 thrombi were correctly diagnosed with high accuracy, but via
      CT none. CONCLUSION: In early stage renal carcinoma CT and MR imaging yielded
      similar staging accuracies. In advanced renal carcinoma MRI was superior to CT
      imaging, especially in diagnosing tumour thrombus. Consequently the extent of
      tumour thrombus may be assessed by MRI which may therefore replace conventional
      cavography.

PMID- 9519048
TI  - [Spiral CT and MRT of the operated Stanford-type-A aortic dissection: its course
      and complications].
AB  - PURPOSE: To demonstrate normal postoperative spiral CT and MRI findings and
      typical complications in patients with aortic repair after Stanford type A aortic
      dissection. METHODS: 24 patients with aortic repair after Stanford type A aortic
      dissection were followed up by spiral CT and MRI (0.5 Tesla). Presence of
      persistent dissection, progressive or new dissection, proximal and distal
      anastomosis, periprosthetic space, supraaortic vessels, thrombosis and dilatation
      of the true and false lumen were evaluated. RESULTS: The following postoperative
      complications were seen: three pseudoaneurysms which developed at the proximal
      anastomoses of the Dacron prosthesis in two cases and at the insertion site of
      the reimplanted left coronary artery after implantation of a composite graft
      (Bentall procedure) in one case; one re-dissection; one perforation of the false
      lumen; periprosthetic flow in one patient after surgical repair of type A
      dissection by the graft inclusion technique; progressive dilatation of the false
      lumen in 4 cases; dilatation of the aortic root in a Marfan patient after
      replacement of the ascending aorta. CONCLUSION: Precise knowledge of the surgical
      technique performed is crucial to accurate postoperative imaging evaluation. MRI
      is the method of choice in the postoperative follow-up of clinically stable
      patients with aortic dissections.

PMID- 9519050
TI  - [Embolization with gelatin-impregnated microspheres].
AB  - PURPOSE: This paper presents a new, easy to handle material for embolisation
      which comes up with sharply defined particle size and spherical shape, very
      suitable for peripheral embolisation in the small end arteries. METHODS: In 13
      superselective embolisations with coaxial catheters the gelatine coated
      microspheres-sized 300-500, 500-700, 700-900 microns--were injected in the region
      of bronchial arteries (n = 7), vertebral bodies (n = 4) and pudendal arteries (n
      = 2). RESULTS: In all cases complete occlusion of the desired vessels was
      achieved. With the exception of one transient dysesthesia in the relevant
      dermatome during embolisation of the third lumbal vertebra, no adverse effects
      were noted. The microspheres were suspended in contrast medium and could be
      easily located by indirect methods, and hence the embolisation procedure was well
      controlled. DISCUSSION: Compared with other embolisation materials the ready-for
      use gelatine coated microspheres due to their physical properties are an
      excellent alternative to superselective embolisation materials of end arteries.

PMID- 9519051
TI  - [The possibilities and risks of outpatient PTA in patients with peripheral
      arterial obstructive disease].
AB  - PURPOSE: To evaluate risk and feasibility of outpatient PTA in patients with
      iliac-femoral artery disease we conducted a prospective study. MATERIAL AND
      METHOD: Out of a total group of 263 patients we selected 100 p. (38%) according
      to pre-defined criteria. The following criteria and others excluded the patients
      from outpatient procedures: insulin-dependent diabetes, poorly controlled
      hypertension, cardiac failure grade III and IV, chronic haemodialysis, severe
      overweight, elective stent implants. RESULTS: 90 of 100 patients for whom we had
      planned an outpatient procedure, could leave the day-clinic after a maximum of 10
      hours of observation. For 10 patients we changed the procedure to an inpatient
      stay because of prolonged heparinisation, sudden elevation of arterial pressure,
      secondary stent implants and the need for local fibrinolysis therapy.
      Complications showed a trend to be lower in the outpatient group than in the
      inpatient group (2.0% vs 4.3%). CONCLUSIONS: Performing iliac-femoral PTA on an
      outpatient basis demands strict selection criteria and a close tie-up to a day
      clinic. In 2/3 of our patients we preferred to perform PTA on an inpatient basis.
      A higher incidence of risks was seen in the inpatient group.

PMID- 9519052
TI  - [Spiral CT in arytenoid cartilage dislocation: the optimization of the study
      parameters with a cadaver phantom and its clinical evaluation].
AB  - PURPOSE: To evaluate an optimal scan protocol in a cadaver phantom and its
      clinical assessment in 40 patients. MATERIALS AND METHODS: In a cadaver larynx
      phantom helical CT (HiSpeed Advantage; GE, Milwaukee, Wis) was performed with
      increasing collimation (1-10 mm) and pitch (1.0-3.0). 40 patients with an
      immobile vocal cord were randomly assigned to undergo CT with a certain protocol.
      RESULTS: Best resolution was obtained with a collimation of 1 mm and pitch 1. The
      pitch could be increased up to 2 without losing information. With a collimation
      of 3 mm and higher, anatomical details were missed. In the patient studies a
      combination of 1 mm collimation with a pitch of 2.0 showed less motion artifacts
      than a pitch of 1.0. CONCLUSION: The quality of CT imaging of the arytenoid
      cartilage depends greatly on the scanning parameters, the compliance of the
      patients and the mineralisation of the cartilage. For clinical assessment a
      collimation of 1 mm with a pitch of 2 is recommended. The increase pitch has the
      advantage of shorter acquisition times and decreased radiation exposure.

PMID- 9519053
TI  - [Magnetization transfer contrast: experimental sequence optimization for study of
      the cerebral substantia alba].
AB  - PURPOSE: A new application for magnetization transfer (MT) MR imaging is the
      investigation of cerebral white matter. For that a pure MT effect is desirable.
      Our purpose was the optimization and testing of an MT sequence for investigations
      of cerebral white matter. MATERIAL AND METHODS: Experimental investigations were
      performed in phantom material and in 5 wistar rats using various frequency
      offsets (FO) (200 Hz-30,000 Hz). Relative signal suppression (rSS) for the
      phantom material and for callosal white matter of the rat was calculated. The
      optimized sequence was tested in 25 healthy volunteers. RESULTS: A relatively
      pure MT effect was achieved with FO > 4000 Hz. rSS for cerebral white matter
      structures was generally higher than rSS fur cerebral gray matter structures. rSS
      for cerebral white matter structures ranged from 45-50%. CONCLUSION: We present a
      fast MT sequence with high rSS for cerebral white matter and a relatively pure MT
      effect. Owing to the high rSS-values we expect that this sequence improves
      differentiation of cerebral white matter lesions. Because of the confusing
      variety of MT sequence currently described in the literature we believe that
      standard parameters should be defined to make published results comparable.

PMID- 9519054
TI  - [Suction pump-supported aspiration thrombectomy: an in-vitro comparison with a
      thrombus fragmentation procedure].
AB  - PURPOSE: To compare the efficacy of vacuum pump controlled aspiration
      thrombectomy (VPCAT) with the Amplatz thrombectomy device (ATD) for treatment of
      thrombotic occlusions. MATERIALS AND METHODS: In a flow-model a superficial
      femoral artery is simulated. VPCAT provides the connection either of an
      aspiration catheter (AC, 8 F) or a multipurpose catheter (MPC, 8 F) with a vacuum
      pump (-110 mbar underpressure). 7 day old porcine blood (n = 30; 7.4 g +/- 0.1g)
      was treated with AC and MPC (VPCAT technique) and with the ATD. RESULTS: Complete
      thrombectomy was achieved with all techniques. Thrombectomy time was short for
      ATD (8.8 +/- 0.94 s; p < 0.01). MPC caused the least overall weight of emboli
      related to thrombus weight (5.14 0/100; p < 0.01). ATD caused the least embolisms
      at 1000 microns (3.27 mg; p < 0.05), and the most embolisms at 100 microns and at
      10 microns (26.5 mg and 26.9 mg; p < 0.01). The aspirated volume of the MPC (33
      +/- 17 ml) was half the volume of the AC (65 +/- 25 ml). CONCLUSIONS: In-vitro,
      VPCAT proves to be an alternative procedure to ATD. The use of a wide lumen
      multipurpose catheter is advantageous. In vitro, embolism rates of all methods
      are sufficiently low.

PMID- 9519055
TI  - [Precise MR-guided preoperative marking of breast lesions with an embolization
      coil using a standard MR coil].
AB  - PURPOSE: To develop and test a new technique for MR-guided localisation of breast
      lesions. MATERIALS AND METHODS: The examinations were performed on a 1.0 T imager
      in prone position, using a sagittally oriented oval spine coil. The localization
      device consisted of a perforated lateral plate which can be angulated. The plate
      contained an "M" shaped tube filled with oil. This enabled exact localization of
      the lesion in relation to the bore holes on the MR images. After needle placement
      through a sterile bushing, the 5 mm marking coil was placed through the needle
      adjacent to the lesion. Then a suspension of charcoal, Gd-DTPA, and water was
      injected. Suspicious lesions that could be visualised only by MR were localised
      preoperatively and marked in 6 patients. RESULTS: The lesion size ranged from 0.5
      to 3.5 cm (median 1.2 cm). Three benign lesions (intraductal hyperplasia twice,
      radial scar once) and three malignant lesions (ductal invasive cancer twice, DCIS
      once) were found. Angulation of the plate was beneficial in three cases.
      CONCLUSION: With the new marking technique, exact MR-guided localization of
      breast lesions using an add-on device is feasible. Construction of an additional
      MR coil is not necessary. Excision of the lesion is proven by the concomitant
      excision of the marking coil.

PMID- 9519056
TI  - [A rare complication after cardiopulmonary resuscitation with a fatal outcome].

PMID- 9519058
TI  - [Intracranial plasma-cell granuloma].

PMID- 9519057
TI  - [An epidermoid of the sphenoid bone and a ruptured intracranial dermoid--a case
      report].

PMID- 9519059
TI  - [New algorithms for the diagnosis of pulmonary embolism without perfusion
      SPECT?].

PMID- 9519060
TI  - Mental health and ethnicity: an Irish dimension.

PMID- 9519061
TI  - Which atypical antipsychotic.

PMID- 9519062
TI  - Brain abnormality in schizophrenia. A systematic and quantitative review of
      volumetric magnetic resonance imaging studies.
AB  - BACKGROUND: Numerous in vivo brain imaging studies suggest that cerebral
      structure is abnormal in schizophrenia, but implicate different regions to
      varying extents. METHOD: We identified published MRI studies in schizophrenia
      with searches of the computerised literature and key journals. Reports giving the
      volumes of cortical structures in people with schizophrenia and controls were
      included. The percentage differences in volumes were calculated and the median
      taken as a summary measure for each brain region. RESULTS: Forty relevant studies
      were identified. The median percentage volume differences revealed overall
      reductions in the whole brain (3%), temporal lobe (6% left, 9.5% right), and the
      amygdala/ hippocampal complex (6.5%, 5.5%); and increases in the lateral
      ventricles (44%, 36%), that were greatest in the body and occipital horns.
      Segmentation studies suggest that grey matter is reduced but that white matter
      volumes may actually be increased. In men, substantial reductions were also
      evident in the amygdala and hippocampus, as well as the largest reductions of all
      in the parahippocampus (14%, 9%). Few studies gave figures for women alone.
      CONCLUSIONS: Several brain structures in schizophrenia are affected to a greater
      extent than expected from overall reductions in brain volume. Further studies are
      required in affected women, and to try to identify clinical and aetiological
      associations of these findings.

PMID- 9519063
TI  - Protocol for assessing services for people with severe mental illness.
AB  - BACKGROUND: The Clinical Standards Advisory Group was asked by UK health
      ministers to advise on the standards of clinical care being achieved for people
      with schizophrenia. A subcommittee commissioned a review of standards, followed
      by research into how far these were reflected in contracts and met by providers.
      METHOD: No comprehensive but practical set of standards was found. A protocol of
      143 items of good service practice was constructed, and applied by teams visiting
      services in II UK districts. The team appraisals were summarised in 20 key
      points, each scored 0 (absent) to 4 (excellent performance). Seven points were
      used to assess standards of commissioning and 13 for standards of service
      provision. RESULTS: When placed into rank order, the mean key point scores for
      commissioners and providers in the same district tended to be very similar. Total
      district scores were then used to assign districts to one of three groups. Four
      performed reasonably well, five were moderate and two were poor. CONCLUSIONS: One
      of the key elements associated with these differences was the local level of
      morale. After wide consultation, a revised protocol of 26 key points for direct
      rating was drawn up and has since been further tested.

PMID- 9519064
TI  - Linguistic performance in children who develop schizophrenia in adult life.
      Evidence for normal syntactic ability.
AB  - BACKGROUND: Less syntactically complex speech in patients with schizophrenia has
      been thought to represent a premorbid dysfunction, of possible prognostic value
      and indicative of a neurodevelopmental origin for schizophrenia. METHOD:
      Narratives written at age 11 by children who then developed psychiatric disorders
      in adult life (using PSE CATEGO diagnoses), especially schizophrenia, were
      compared with matched controls on syntactic complexity, syntactic maturity,
      grammatical deviance and spelling ability. RESULTS: Children who later developed
      either schizophrenia, affective psychosis or a neurotic type of disorder in
      adulthood did not differ from normal controls on any of the measures of syntactic
      production, grammatical errors or spelling. CONCLUSIONS: It is probable that
      previous reports of reduced syntactic complexity in schizophrenic speech are a
      consequence of being in a psychotic state and do not represent a premorbid
      deficit.

PMID- 9519065
TI  - 'Cloze' procedure refined and modified. 'Modified Cloze', 'reverse Cloze' and the
      use of predictability as a measure of communication problems in psychosis.
AB  - BACKGROUND: 'Cloze' procedure assesses the predictability of text by deleting
      words at set intervals and having a panel of raters fill the blanks. Two
      refinements to the procedure are described: 'modified Cloze' and 'reverse Cloze',
      the latter examining the subject's ability to interpret a partial transcript.
      METHOD: Samples of speech were obtained from patients with schizophrenia, manic
      depression and orthopaedic disorders using a standard prompt, and the output
      analysed using modified Cloze. In addition, subjects completed a reverse Cloze
      passage. RESULTS: Both modified Cloze and reverse Cloze discriminated the
      performance of patient groups, with patients with schizophrenia performing worst.
      CONCLUSIONS: These techniques extend earlier findings suggesting reduced
      predictability in psychotic speech, particularly for patients with schizophrenia.
      The reverse Cloze procedure suggests a 'mirror-image' deficit and is a potential
      objective index of psychopathology that is much simpler to apply than traditional
      Cloze.

PMID- 9519066
TI  - Lateralised semantic and indirect semantic priming effects in people with
      schizophrenia.
AB  - BACKGROUND: In schizophrenia, disturbances in the development of physiological
      hemisphere asymmetry are assumed to play a pathogenetic role. The most striking
      difference between hemispheres is in language processing. The left hemisphere is
      superior in the use of syntactic or semantic information, whereas the right
      hemisphere uses contextual information more effectively. METHOD: Using
      psycholinguistic experimental techniques, semantic associations were examined in
      38 control subjects, 24 non-thought-disordered and 16 thought-disordered people
      with schizophrenia, for both hemispheres separately. RESULTS: Direct semantic
      priming did not differ between the hemispheres in any of the groups. Only thought
      disordered people showed significant indirect semantic priming in the left
      hemisphere. CONCLUSIONS: The results support: (a) a prominent role of the right
      hemisphere for remote associations; (b) enhanced spreading of semantic
      associations in thought-disordered subjects; and (c) disorganisation of the
      functional asymmetry of semantic processing in thought-disordered subjects.

PMID- 9519067
TI  - First episodes of psychosis in Afro-Caribbean and White people. An 18-year follow
      up population-based study.
AB  - BACKGROUND: There have been few prospective studies of the long-term outcome of
      psychosis in people of Afro-Caribbean origin in the UK. METHOD: We followed-up a
      population-based, consecutive series of 34 Afro-Caribbean and 54 White people
      with psychosis who had been extensively investigated during their first admission
      in 1973/74. Diagnoses were made by direct interview using the Present State
      Examination at both first admission and follow-up. RESULTS: Ninety-seven percent
      of the original sample were traced. A slightly greater proportion of the Afro
      Caribbean people were assigned to the S+ Catego class (schizophrenia), both on
      first assessment and at follow-up. No difference was found between the two groups
      in the consistency of diagnosis over the 18 years or in the proportion of
      patients considered psychotic but Afro-Caribbean people tended to have fewer
      negative symptoms at follow-up. There were striking differences between the two
      groups in their experience of psychiatric care; Afro-Caribbean people were more
      likely to have been readmitted, to have experienced longer hospitalisations, and
      to have undergone more involuntary admissions than their White counterparts.
      CONCLUSIONS: Afro-Caribbean people who met clinical and research criteria for
      schizophrenia had a less satisfactory experience of, and response to, psychiatric
      care over 18 years than their White counterparts.

PMID- 9519068
TI  - Longitudinal study of interpersonal dependency in female twins.
AB  - BACKGROUND: Interpersonal dependence is thought to be important in a number of
      physical and psychological disorders. There are several developmental theories
      that suggest environmental influences in childhood are important. METHOD: A twin
      study methodology was used to look at the genetic and environmental influences on
      interpersonal dependence as measured by a sub-scale of the Interpersonal
      Dependency Inventory with a population-based sample of 2230 twins. RESULTS:
      Psychometric analysis revealed that this was a stable measure and that there was
      a substantial degree of construct validity. Both univariate and longitudinal twin
      analysis suggested that there was a modest genetic influence and a large,
      specific environment influence on interpersonal dependency as measured by this
      scale. The longitudinal analysis revealed that the genetic influence was stable
      over the time-scale sampled and the environmental influence was moderately
      stable. CONCLUSIONS: This finding is at odds with theories that suggest shared
      environment is important in the aetiology of interpersonal dependency.

PMID- 9519069
TI  - Disability pensions in severely disturbed in-patient adolescents. Twenty-year
      prospective study.
AB  - BACKGROUND: Knowledge of working capacity from adolescence until adulthood among
      severely disturbed in-patients is scarce. METHOD: In a follow-up study of 61
      adolescent in-patients, we studied associations between being on a disability
      pension 20 years after hospitalisation, and the patients' psychopathology and
      treatment-related factors during the hospitalisation and seven-year follow-up.
      RESULTS: Of the former in-patients, 27% had not been on a disability pension, 20%
      had short-term pension periods, and 53% were pensioned. Subjects whose overall
      psychosocial functioning had improved and who had not utilised in-patient
      services until the seven-year follow-up, had a better prognosis in terms of
      working capacity. Half of the subjects who had not been on pension during the
      follow-up had received a diagnosis of conduct disorder at discharge, and half of
      those pensioned had a psychotic disorder. CONCLUSIONS: The patients' level of
      psychosocial functioning and capability to work in young adulthood were
      associated with long-term prognosis in terms of working capacity. Adolescence
      seems to be the critical time for intensive psychiatric care combined with
      vocational rehabilitation programmes.

PMID- 9519070
TI  - Epidemiology of recurrent major and minor depression with a seasonal pattern. The
      National Comorbidity Survey.
AB  - BACKGROUND: Previous estimates of the prevalence of seasonal affective disorder
      (SAD) in community samples have been in the range 2-10%, using methods not
      derived from DSM algorithms. We report the first community-based study to
      estimate major and minor depression with a seasonal pattern in a community-based
      sample using a diagnostic instrument derived from DSM-III-R. METHOD: A modified
      version of the Composite International Diagnostic Interview was administered to
      8098 subjects in the 48 coterminous states of the USA (the National Comorbidity
      Survey) to assess the prevalence of major and minor depression with a seasonal
      pattern. RESULTS: The lifetime prevalence of major depression with a seasonal
      pattern was 0.4%, and the prevalence of major or minor depression with a seasonal
      pattern was 1.0%. Among respondents with major depression, male gender and older
      age were associated with a higher prevalence with a seasonal pattern.
      CONCLUSIONS: Prevalence estimates of major and minor depression with a seasonal
      pattern are much lower than those found in previous studies of SAD in the
      community, probably due to the approach to diagnosis used in the present study,
      which more accurately represents DSM-III-R criteria for major depression with a
      seasonal pattern. The distribution of the disorder is similar to that found in
      previous studies except for the higher prevalence among males.

PMID- 9519071
TI  - Alcohol use disorders among the Yami aborigines in Taiwan. An inter-ethnic
      comparison.
AB  - BACKGROUND: Alcohol use disorders (AUDs) among the Yami aborigines in Taiwan were
      investigated and compared with four other taiwanese aboriginal groups. METHOD: A
      sample survey was conducted using a semi-structured clinical interview for AUDs
      among 252 subjects, aged 15 and above, from two Yami villages on Orchid Island.
      RESULTS: The prevalences of DSM-III-R and DSM-IV alcohol use disorders were 13.1%
      and 10.3% by one year, and 17.5% and 15.2% by lifetime, respectively, with a male
      excess. The risk for AUDs in Yami men was significantly associated with a lower
      educational level, a non-married status, and the length of stay in mainland
      Taiwan. A protective effect of Christian belief was evident for lifetime risk for
      AUDs. CONCLUSIONS: The lower prevalences of AUDs in Yami than in other aboriginal
      groups in Taiwan might be explained by social isolation of the former, and
      differences in drinking tradition, availability of alcohol, biological
      vulnerability, and the extent of acculturation between these groups.

PMID- 9519072
TI  - Fluoxetine in breast-milk and developmental outcome of breast-fed infants.
AB  - BACKGROUND: Selective serotonin reuptake inhibitors are currently the most widely
      prescribed antidepressant drugs. There are only four published studies of breast
      feeding mothers and their infants in which the mothers were taking fluoxetine.
      METHOD: Four mothers who took fluoxetine and their breast-fed infants were
      studied. Samples of plasma, breast-milk and urine were taken from the mothers and
      of plasma and urine from infants for assays of drug and metabolite
      concentrations. Bayley Scales of Infant Development were repeatedly used to
      assess cognitive and psychomotor development of the infants. RESULTS: Fluoxetine
      and norfluoxetine were detected in all samples of maternal plasma (range of total
      concentration 138-427 ng/ml) and in breast-milk (range 39-177 ng/ml). Amounts of
      both fluoxetine and norfluoxetine in infants' plasma and urine were below the
      lower limit of detection. All infants were observed to be developing normally and
      showed no abnormal findings on neurological examination. CONCLUSIONS: Much larger
      databases are needed but these four cases do not provide any evidence to suggest
      that women who are maintained on therapeutic doses of fluoxetine should
      discontinue breast-feeding their infants if they wish to breast-feed.

PMID- 9519073
TI  - Chromosome 22qII deletions. An under-recognised cause of idiopathic learning
      disability.
AB  - BACKGROUND: Velo-cardio-facial syndrome (VCFS), a syndrome of multiple congenital
      abnormalities including characteristic dysmorphology, congenital heart defects
      and learning disability, is associated with small interstitial deletions of
      chromosome 22qII. We tested the hypothesis that VCFS may be significantly under
      diagnosed by screening a learning disabled population for chromosome 22qII
      deletions. METHOD: Two hundred and sixty-five people with learning disability
      residing in two learning disability hospitals in South Wales were reviewed. They
      were selected for inclusion in the study if they fulfilled any of the following
      criteria: psychotic disorder (schizophrenia or affective disorder), family
      history of psychotic disorder, cleft palate and/or lip, congenital heart disease,
      broadly defined facial dysmorphism or a history of hypocalcaemia. Fluorescence in
      situ hybridisation studies were performed on 74 selected individuals. RESULTS:
      Cytogenetic analysis revealed that two people demonstrated a previously
      undetected chromosome 22qII deletion. A third person demonstrated a previously
      undetected cytogenetically visible deletion on chromosome 15. CONCLUSIONS: VCFS
      appears to be aetiologically significant in a proportion of individuals with
      idiopathic learning disability, especially in those where psychosis is associated
      with mild learning disability. We suggest that clinicians should consider a
      chromosome 22qII deletion in people who meet selection criteria.

PMID- 9519074
TI  - Polydactyly and psychosis. Five cases of co-occurrence.
AB  - BACKGROUND: Abnormalities presumed to occur during foetal life have been
      associated with schizophrenia. Polydactyly is a developmental abnormality but no
      previous association has been reported between polydactyly and functional
      psychotic illness. METHOD: Individuals with both polydactyly and a functional
      psychosis were ascertained during a study of familial schizophrenia. RESULTS:
      Five such individuals were ascertained in the course of assessing 234 individuals
      with familial psychosis, giving a rate of polydactyly in the sample of around 10
      times the general population rate. CONCLUSIONS: This study provides preliminary
      evidence that polydactyly is over-represented in individuals with familial
      schizophrenia and related psychotic illnesses.

PMID- 9519075
TI  - Marked improvement in tardive dyskinesia following treatment with olanzapine in
      an elderly subject.

PMID- 9519076
TI  - Increased prolactin responses to d-fenfluramine in obsessive-compulsive disorder.

PMID- 9519077
TI  - Variability in cognitive deterioration in schizophrenia.

PMID- 9519078
TI  - Obsessional personality and outcome of panic disorder.

PMID- 9519079
TI  - Structural neuroimaging in learning disability.

PMID- 9519080
TI  - Closing the gap between research and practice.

PMID- 9519081
TI  - Doctor's dress.

PMID- 9519082
TI  - Doctor's dress.

PMID- 9519083
TI  - Anorexia and the overvalued idea.

PMID- 9519084
TI  - Reports on psychotherapy commissioned by the National Health Service Executive.

PMID- 9519085
TI  - Liver transplantation for alcoholic liver disease.

PMID- 9519086
TI  - Eugeria, longevity and normal ageing.

PMID- 9519087
TI  - Excess mortality of schizophrenia. A meta-analysis.
AB  - BACKGROUND: This paper presents a structured review of the published information
      on the mortality of schizophrenia. METHOD: A meta-analysis of the literature.
      RESULTS: Schizophrenia has a significantly increased mortality from natural and
      unnatural causes. Twenty-eight percent of the excess mortality is attributable to
      suicide and 12% to accidents. The rest of the excess mortality is from the same
      broad range of conditions which cause deaths in the general population. Further
      interpretation is hampered by confounding variables, wide confidence intervals
      and reservations about generalising from individual cohorts. CONCLUSIONS: The
      available evidence suggests that schizophrenia is associated with a large
      increased mortality from suicide and a moderate increased mortality from natural
      causes. A number of possible interventions have been identified, but we do not
      yet have reliable means of detecting any changes in mortality which might result.

PMID- 9519088
TI  - Costs of schizophrenia.
AB  - BACKGROUND: Schizophrenia is a common and burdensome illness, with implications
      not only for the health service but for a host of other care agencies--public and
      private--as well as for patients, families and the wider society. METHOD: The
      paper reviews available UK evidence on the cost of schizophrenia (broadly
      defined) and on the cost-effectiveness of treatment options and alternative care
      arrangements. New evidence potentially alters our view of the costs of this
      illness. RESULTS: Aggregating the identifiable direct and indirect costs of
      schizophrenia for England suggests an annual cost of 2.6 billion pounds, but even
      this sum omits some indirect impacts which cannot currently be costed. Just over
      half the identified total is accounted for by the direct costs falling to the
      NHS, local authorities, charities and the criminal justice system. In helping to
      tackle this cost burden, there is now a body of evidence on cost-effective
      community care arrangements, antipsychotic drugs and psychological interventions.
      CONCLUSIONS: Although the costs of schizophrenia are considerable, there are
      treatments and care arrangements which can reduce this aggregate burden while
      maintaining or improving effectiveness.

PMID- 9519089
TI  - Minor psychiatric disorder in NHS trust staff: occupational and gender
      differences.
AB  - BACKGROUND: It is widely suggested that many National Health Service (NHS)
      workers experience high levels of minor psychiatric disorder. However,
      inadequacies of sampling and measurement in studies to date have not allowed this
      suggestion to be properly evaluated. METHOD: The present study was designed to
      overcome these methodological weaknesses by using a sample of over 11,000
      employees from 19 NHS trusts and a well-established measure of minor psychiatric
      disorder for which there are comparative data. RESULTS: The findings show that
      26.8% of the health service workers reported significant levels of minor
      psychiatric disorder, compared with 17.8% of people in the general population.
      Psychiatric morbidity was highest among managers, doctors, nurses and professions
      allied to medicine, with each of these groups recording higher rates than their
      professional counterparts outside the health service. It was lower among those in
      support occupations, such as administrative and ancillary staff. A feature of the
      findings was that female doctors and managers showed a much higher prevalence of
      minor psychiatric disorder than their male colleagues. CONCLUSION: Studies are
      required to establish the organisational, occupational and individual
      determinants of minor psychiatric disorder among NHS employees.

PMID- 9519090
TI  - Brazilian multicentric study of psychiatric morbidity. Methodological features
      and prevalence estimates.
AB  - BACKGROUND: Psychiatric morbidity studies in developing countries have used
      diagnostic procedures of low reliability, without a clinical definition of
      caseness, producing descriptive data with limited application for mental health
      planning. METHOD: A two-stage cross-sectional design (with a sample size of 6476)
      was conducted to estimate the prevalence of DSM-III psychiatric diagnoses in
      three metropolitan areas of Brazil (Brasilia, Sao Paulo and Porto Alegre). All
      subjects were screened for the presence of psychopathology with a 44-item
      instrument (the QMPA) and a subsample was selected for a psychiatric interview.
      RESULTS: Age-adjusted prevalence of cases potentially in need of care ranged from
      19% (Sao Paulo) to 34% (Brasilia and Porto Alegre). Anxiety disorders comprised
      the highest prevalences (up to 18%). Alcoholism yielded the most consistent
      prevalence levels, around 8% in all sites. Depression showed great variation
      between areas: from less than 3% (Sao Paulo and Brasilia) to 10% (Porto Alegre).
      CONCLUSIONS: Overall prevalences were high in comparison with previous studies
      conducted in Brazil. A female excess of non-psychotic disorders (anxiety,
      phobias, somatisation and depression) and a male excess for alcoholism were
      consistently found.

PMID- 9519091
TI  - Urban environment and mental health. A longitudinal study.
AB  - BACKGROUND: In a follow-up survey from Oslo, 503 persons were re-interviewed
      using the same questionnaire after 10 years. METHOD: The questionnaire includes
      questions about social support, social characteristics of the neighbourhood and
      mental health. Information about the neighbourhood was also gathered from key
      informants. RESULTS: Of the five types of neighbourhoods surveyed, only one
      showed marked change over time with respect to social characteristics. This was
      an initially poorly functioning neighbourhood with poor mental health among the
      residents, where substantial improvements took place as part of the further
      development of the area. Parallel with the improvement in social environment
      there was a significant improvement in mental health among those who continued to
      live in the same area, as opposed to those who continued to live in the other
      areas. Selective migration could not explain this finding. CONCLUSIONS: The
      findings support the environment stress hypothesis, implying that the quality of
      a neighbourhood has an impact on mental health. The implications for psychiatric
      prevention are discussed.

PMID- 9519093
TI  - Prevalence and significance of weight and shape concerns in girls aged 11-16
      years.
AB  - BACKGROUND: The prevalence of the core ideational component of eating disorders
      among the at-risk population (11-to 16-year-old girls) is not known. METHOD: A
      community survey of 11- to 16-year-old girls was conducted to establish the
      prevalence of significant concerns about body weight and shape characteristics of
      eating disorders. A total of 1068 girls were screened and 368 interviewed using
      standardised measures. RESULTS: Significant weight and/or shape concerns were
      estimated to be present in 14.5% of the 11-to 12-year-olds, 14.9% of the 13-to 14
      year-olds and 18.9% of the 15-to 16-year-olds. Only among those aged 15 to 16 was
      the presence of such concerns associated with a significant level of concurrent
      behavioural and ideational disturbance. CONCLUSIONS: Significant concerns about
      weight or shape are present in almost one in five 15-to 16-year-old girls, many
      of whom evidence high levels of ancillary disturbance.

PMID- 9519092
TI  - Determinants of general practitioner recognition of psychological problems in a
      multi-ethnic inner-city health district.
AB  - BACKGROUND: With few exceptions, evaluation of the capacity of general
      practitioners (GPs) to recognise psychiatric disorder in their patients has
      failed to consider the role of ethnic diversity in the consultation process and
      whether such knowledge can improve understanding of the degree to which
      psychiatric morbidity is recognised within GP settings. METHODS: This research
      was completed in five general practices representative of all those within an
      inner-city health district. Psychiatric morbidity in patients consecutively
      attending the practices was then assessed using the General Health Questionnaire;
      in addition, GPs were asked to complete a checklist of current problems
      identified during each consultation. RESULTS: Analysis suggested that Asian and
      Black patients were less likely than White patients to have psychological
      problems identified; that social problems and a psychiatric history facilitated
      recognition; and that current physical illness hindered recognition. CONCLUSIONS:
      GP recognition of psychological problems varies according to patient ethnicity
      but can be substantially masked by both the physical and social circumstances of
      patients at consultation.

PMID- 9519094
TI  - Family functioning and life events in the outcome of adolescent anorexia nervosa.
AB  - BACKGROUND: This study investigates the outcome of anorexia nervosa in
      adolescents in relation to precipitating life events and changes in family
      functioning over time. METHOD: Thirty-five adolescents with anorexia nervosa and
      their mothers were administered measures of life events and family functioning at
      initial assessment and 1 and 2 year follow-up, when outcome was also assessed.
      RESULTS: Fifty-five per cent of patients had a good outcome. Patients from
      initially well-functioning families or those with precipitating life events
      improved more in the first year, than those with dysfunctional families or
      without events. Subjects perceived a deterioration in family functioning at 1
      year follow-up but an improvement at 2 years. Mothers reported no changes.
      CONCLUSIONS: Approximately half of a series of early onset cases of anorexia
      nervosa can be expected to recover by 2 years. Healthy family functioning and
      presence of a precipitating life event predict good short-term outcome. The
      relationships between subjects' perceptions of family functioning and their
      recovery from anorexia nervosa is discussed.

PMID- 9519095
TI  - Postnatal depression and elation among mothers and their partners: prevalence and
      predictors.
AB  - BACKGROUND: Correlates and predictors of mood disturbances at 3 days and 6 weeks
      postpartum were assessed in Irish mothers and their partners. METHOD: The
      Edinburgh Postnatal Depression Scale (EPDS) and the Highs Scale were used to
      assess 370 mothers and their partners. Socio-demographic, clinical and obstetric
      data were collected at patients' first antenatal visit. Factors associated with
      EPDS scores of > or = 13 and Highs score of > or = 8 were examined. RESULTS: On
      the EPDS 11.4% of mothers scored > or = 13 at 3 days postpartum and 11% at 6
      weeks, while 18.3% of mothers scored > or = 8 on the Highs Scale at 3 days and 9%
      at 6 weeks. Scores on the EPDS and Highs Scale were interrelated. Factors
      associated with EPDS scores of > or = 13 at 6 weeks were single status,
      unemployment, unplanned pregnancy, public status and bottlefeeding. The best
      predictors of EPDS > or = 13 at 6 weeks were mothers' scores on the EPDS and the
      Highs Scale at 3 days. Three per cent of partners scored > or = 13 on the EPDS at
      3 days postpartum and 1.2% at 6 weeks. CONCLUSIONS: Factors associated with
      mothers' mood disturbance were readily identifiable and collected routinely at
      antenatal intake. Mothers' mood within 3 days of delivery was the best predictor
      of later postnatal depression. Paternal mood disturbance was rare. Certain women
      may be at increased risk for postnatal mood disturbance and may be amenable to
      early identification and intervention.

PMID- 9519096
TI  - Trends in deliberate self-harm in Oxford, 1985-1995. Implications for clinical
      services and the prevention of suicide.
AB  - BACKGROUND: Deliberate self-harm (DSH) has been a major health problem in the UK
      for nearly three decades. Any changes in rates of DSH or the demographic
      characteristics of the patient population are likely to have important
      implications for clinical services and suicide prevention. METHOD: Data collected
      by the Oxford Monitoring System for Attempted Suicide were used to review trends
      in DSH between 1985-1995. RESULTS: There was a substantial increase in DSH rates
      during the 11-year study period, with a 62.1% increase in males and a 42.2%
      increase in females. The largest rise was in 15-24-year-old males (+ 194.1%).
      Changes in DSH rates correlated with changes in national suicide rates in both
      males and females in this age group. Rates of repetition of DSH increase in both
      genders during the study period. Paracetamol self-poisoning has continued to
      increase, half of all overdoses in 1995 involving paracetamol, and antidepressant
      overdoses have become more common. CONCLUSIONS: The increase in DSH, especially
      in young males, has important implications for general hospital DSH and medical
      services. It may herald a reversal of recent progress towards achievement of
      national suicide targets.

PMID- 9519097
TI  - Suicide among psychiatric in-patients in a changing clinical scene. Suicidal
      ideation as a paramount index of short-term risk.
AB  - BACKGROUND: Rapid changes in styles of clinical practice mean that we should
      carefully monitor the way suicides occur among psychiatric patients both in
      hospital and in the wider community. METHOD: Patients who had died through
      suicide either while receiving in-patient care or within 2 months of discharge
      from hospital were compared with a similar series reported 10 years previously.
      Clinicians' perceptions of patients' behaviour were compared with concurrent
      controls. RESULTS: Patients in the more recent study were younger, more often
      male, and a greater proportion had been discharged from in-patient status.
      Hazards which complicated risk assessment included short-lasting misleading
      clinical improvements, variability in degree of distress, and a reluctance to
      discuss suicidal ideas. Over a range of perceived behaviours it was not possible
      to distinguish suicides from controls. CONCLUSIONS: In assessing suicide risk
      paramount importance should be attached to monitoring suicidal ideation and
      addressing the several hazards which might complicate this procedure.

PMID- 9519098
TI  - One-year, low-dose neuroleptic study of in-patients with chronic schizophrenia
      characterised by persistent negative symptoms. Amisulpride v. haloperidol.
AB  - BACKGROUND: Amisulpride is a potent substituted benzamide antipsychotic drug
      claimed to improve the negative symptoms of schizophrenia, particularly at low
      dosage. METHOD: Sixty long-term in-patients with schizophrenia and selected for
      predominant negative symptoms were randomised to receive either haloperidol or
      amisulpride. Over a year there was systematic dose reduction, as symptoms
      allowed. RESULTS: There were no significant differences between the treatment
      groups in the proportion receiving low-dose treatment, the control of positive
      symptoms, or ratings of social behaviour, side-effects or tardive dyskinesia. For
      negative symptoms, there were consistent but non-significant trends in favour of
      amisulpride. The amisulpride patients required significantly less anticholinergic
      medication. CONCLUSIONS: In chronically-hospitalised in-patients with
      schizophrenia characterised by persistent negative symptoms, amisulpride was a
      well-tolerated maintenance antipsychotic medication. The drug had only a limited
      effect in reducing negative symptoms, which were relatively stable, enduring
      phenomena in this sample, despite dosage reduction.

PMID- 9519099
TI  - Sulpiride augmentation in people with schizophrenia partially responsive to
      clozapine. A double-blind, placebo-controlled study.
AB  - BACKGROUND: We hypothesised that a combined regimen of clozapine, a relatively
      weak D2-dopaminergic antagonist, and sulpiride, a selective D2 blocker, would
      demonstrate a greater antipsychotic efficacy by enhancing the D2 blockade of
      clozapine. METHOD: Twenty-eight people with schizophrenia, previously
      unresponsive to typical antipsychotics and only partially responsive to current
      treatment with clozapine, received, double-blind, 600 mg/day sulpiride or
      placebo, in addition to an ongoing clozapine treatment. The clinical status was
      evaluated before, during, and at the end of 10 weeks of sulpiride addition using
      the Brief Psychiatric Rating Scale (BPRS), Scale for the Assessment of Positive
      Symptoms (SAPS), Scale for the Assessment of Negative Symptoms, and Hamilton
      Rating Scale for Depression. RESULTS: The clozapine-sulpiride group exhibited
      substantially greater and significant improvements in positive and negative
      psychotic symptoms. About half of them, characterised by a younger age and lower
      baseline SAPS scores, had a mean reduction of 42.4 and 50.4% in their BPRS and
      SAPS scores, respectively. CONCLUSIONS: A subgroup of patients with chronic
      schizophrenia may substantially benefit from sulpiride addition to clozapine.

PMID- 9519100
TI  - Altered dopaminergic function and negative symptoms in drug-free patients with
      schizophrenia. [123I]-iodobenzamide SPECT study.
AB  - BACKGROUND: Previous in vivo studies of schizophrenia with dopamine D2 receptor
      radioligands have yielded contradictory results. No prior study has used multiple
      scans to examine within-subject clinical change. METHOD: Twenty-one patients were
      studied with [123I]-iodobenzamide single photon emission computed tomography
      about two weeks after neuroleptic withdrawal. Thirteen of the 21 completed a
      second scan about four weeks after neuroleptic withdrawal. Sixteen controls were
      scanned for comparison. RESULTS: There was no significant difference between
      groups in [123I]-iodobenzamide uptake at either scanning session. No significant
      correlations with demographic variables (age, illness duration, drug-free
      period), or clinical ratings (positive and negative symptoms, movement disorder)
      were observed at either scanning session. There was a significant correlation
      between change in [123I]-iodobenzamide uptake and change in negative symptom
      ratings for the subjects who underwent two scans (r = 0.72, P < 0.05).
      CONCLUSIONS: Worsening of negative symptoms may be associated with increased
      availability of striatal D2 receptors, perhaps because of decreased
      concentrations of endogenous dopamine.

PMID- 9519101
TI  - Test of Xq26.3-28 linkage in bipolar and unipolar affective disorder in families
      selected for absence of male to male transmission.
AB  - BACKGROUND: There have been several reports of linkage between genetic markers on
      the X chromosome at Xq26.3-28 and bipolar affective disorder in family samples
      obtained from distinct ethnic and geographical origins. As part of a genome
      search in a series of 23 UK and Icelandic families, specifically selected for
      their large size and power to resolve the issue of linkage heterogeneity, we have
      tested the hypothesis that there is a locus for a genetic subtype of bipolar
      affective disorder which is linked to this region. METHOD: In families selected
      on the basis of absent male to male transmission for affective disorder, we
      performed two-point and FASTMAP multipoint linkage analyses with markers spanning
      the region between the genetic loci DXS102 and F8. RESULTS: We found negative lod
      scores for several models of affection status in families selected under
      stringent and relaxed criteria for the absence of male to male transmission.
      CONCLUSIONS: In the family sample we have obtained, our study provides no support
      for the presence of a locus increasing genetic susceptibility to bipolar
      affective disorder in this region of the X chromosome. It is likely that our
      finding reflects heterogeneity of linkage for bipolar and genetically related
      unipolar disorder that exists in specific ethnic populations. Alternatively the X
      linked subtype of the disorder may have been present only in a few of our small
      families resulting in loss of power to detect the Xq26.3-28 linked subtype.

PMID- 9519102
TI  - Prejudice against providers of psychiatric services for black people.

PMID- 9519103
TI  - Psychological debriefing for victims of acute burn trauma.

PMID- 9519104
TI  - Psychological debriefing for victims of acute burn trauma.

PMID- 9519105
TI  - Psychological debriefing for victims of acute burn trauma.

PMID- 9519106
TI  - Cost-effectiveness of clozapine.

PMID- 9519107
TI  - Cannabis and schizophrenia.

PMID- 9519108
TI  - Depressive delusions and general election.

PMID- 9519109
TI  - Role of GPs in service provision for people with schizophrenia.

PMID- 9519110
TI  - Lethal lithium poisoning with sustained-release preparations.

PMID- 9519111
TI  - Tardive dyskinesia in CYP2D6 polymorphism in Chinese.

PMID- 9519112
TI  - Evidence-based psychiatry.

PMID- 9519113
TI  - Clinical trials: severe mental illness and substance misuse.

PMID- 9519114
TI  - Subjective quality of life and drug treatment for schizophrenia.

PMID- 9519115
TI  - Phonological acquisition of Turkish children: implications for phonological
      disorders.
AB  - The study reported describes the phonological rules typical of normal development
      of Turkish-speaking children. The processes identified include: reduplication,
      syllable deletion, consonant deletion, assimilation, cluster reduction, liquid
      deviation, stopping, fronting, affrication, and backing. From a crosslinguistic
      perspective, the phonological process patterns exhibited coincide broadly with
      universal tendencies, although some language specific patterns were also evident.
      In contrast, a case study of a phonologically disordered child indicated that her
      system was characterised by the use of idiosyncratic phonological rules as well
      as delayed acquisition of some aspects of the system. This atypical pattern
      reflects reports of phonologically disordered children learning other languages.
      The findings indicate that the deficit underlying this type of phonological
      disorder leads to similar phonological behavior irrespective of the language
      being acquired.

PMID- 9519116
TI  - Variability in upper motor neurone-type dysarthria: an examination of five cases
      with dysarthria following cerebrovascular accident.
AB  - The degree of diversity in the nature and extent of the physiological deficits
      which occur in subjects with dysarthria with similar neurological damage is
      demonstrated through the individual assessment profiles of five subjects with
      dysarthria following upper motor neurone (UMN) damage. The perceptual profiles of
      each subject were compiled using perceptual ratings of deviant speech parameters,
      intelligibility ratings from the Assessment of Intelligibility of Dysarthric
      Speech (ASSIDS), and perceptual judgements of subsystem function determined from
      the Frenchay Dysarthria Assessment (FDA). For each individual, the perceptual
      profile of their speech impairments was compared and contrasted with the
      objective results of spirometric and kinematic assessments of respiratory
      function aerodynamic and electroglottographic evaluations of laryngeal function,
      pressure and strain gauge evaluations of articulatory function, and nasal
      accelerometric assessments of nasality. The outcomes of the individual perceptual
      and physiological profiles are discussed with respect to the presence of
      differential subsystem impairments both within each subject and between subjects
      with similar underlying pathophysiological deficits. The importance of
      interpreting the instrumental findings with respect to the interdependency of
      each of the motor speech subsystems, the limitations of perceptual assessments,
      and the advantages of utilising both perceptual and physiological analyses in the
      process of identifying treatment goals is discussed.

PMID- 9519119
TI  - A comparison of three approaches to delivering a speech and language therapy
      service to people with learning disabilities.
AB  - This research aimed to compare three different approaches to delivering a speech
      and language therapy service to people with learning disabilities, in order to
      make recommendations for future service delivery. The three approaches all
      involved working with key communication partners in the environment. They were:
      (i) working directly on a one-to-one basis with the person and partner; (ii)
      working indirectly by providing teaching for partners; and (iii) a combination of
      these two approaches. A teaching course called 'Talkabout' was used. Talkabout
      aims for staff to reach a recognised level of knowledge and competence in
      communication skills, thus facilitating the communication skills of their service
      users. The results indicated that whilst communication changed in all three
      approaches, overall changes were greater in the combination approach. Only the
      combination approach demonstrated statistically significant differences following
      intervention, in terms of staff initiations, service user responses, and their
      use of additional modalities.

PMID- 9519118
TI  - Measurements of temperament in the identification of children who stutter.
AB  - As an empirical check on widely held stereotypes and some assumed temperament
      proclivities of children at risk for stuttering, parents of at-risk children and
      a gender- and age-matched control group completed the 'Parent Childhood
      Temperament Questionnaire for 3-7-Year-Olds'. A discriminant analysis on the nine
      temperament dimensions revealed four dimensions which combined to discriminate
      significantly between the two groups, resulting in correct classification of
      86.36% of the 22 children. The t-tests of difference on the four discriminating
      dimensions revealed that 'Mood', 'Adaptability', and 'Rhythmicity' were
      statistically significant in the direction of more positive temperament for at
      risk children than for the control group. Results are discussed with respect to
      aetiology, stereotype, and the need for clinicians to focus parents on concrete
      behaviours when reporting on the emotional and behavioural style of their child.

PMID- 9519117
TI  - Intelligibility of oesophageal and tracheo-oesophageal speech: preliminary
      observations.
AB  - The purpose of this study was to compare the intelligibility of two types of
      alaryngeal speech commonly used after total laryngectomy. Four male oesophageal
      speakers and four male tracheo-oesophageal speakers read a series of monosyllabic
      words, multisyllabic words and sentences. The monosyllabic word list consisted of
      several minimal pairs for each of eight phonetic contrasts; multisyllabic words
      and sentences were not selected on specific phonetic grounds. Audio recordings of
      all subjects' readings were presented to eight naive adult listeners who
      completed both an item identification task and a scaling procedure. The item
      identification task revealed higher intelligibility fpr tracheo-oesophageal
      speakers than for oesophageal speakers during the monosyllabic word condition.
      Results from the scaling procedure indicated that listeners' subjective
      intelligibility ratings were also higher for the tracheo-oesophageal speakers
      than for the oesophageal speakers. Moreover, a high positive correlation was
      found between the speakers' intelligibility scores obtained from the word
      identification task and the scaling procedure.

PMID- 9519120
TI  - Evaluation of the budget method for screening food additive intakes.
AB  - The Budget Method, originally developed for determining food additive use limits,
      has been proposed as a tool for screening food additive intakes to establish
      monitoring priorities. Theoretical Maximum Daily Intake (TMDI) estimates derived
      using the Budget Method rely on assumptions regarding physiological requirements
      for energy and liquid and on the energy density of food rather than on food
      consumption survey data. This report summarizes work performed to determine the
      validity of Budget Method assumptions and to assess the potential for error in
      assigning monitoring priority based on Budget Method results. Budget Method
      assumptions regarding energy and liquid intake were compared with data from UK,
      German and US nationwide food consumption surveys. It was found that the Budget
      Method assumptions of energy intake and liquid intake are higher than mean
      intakes reported in surveys. The Budget Method assumption regarding energy
      density of foods also was found to be a slight overestimate. Budget Method TMDIs
      for case study additives were in each case larger than survey-based 95th
      percentile per capita additive intake estimates. Based on these results, the
      Budget Method appears to be a suitably conservative screen for establishing
      additive monitoring priorities based on potential lifetime average intakes.

PMID- 9519121
TI  - Residual nitrite and nitrate levels of frankfurters along with their shelf-life.
AB  - Nitrite and nitrate levels of vacuum-packaged frankfurters from four commercial
      brands were tested over 145 days' storage at 3 degrees C. The use of both curing
      salts, KNO3 and NaNO2, was indicated by only two manufacturers on the label.
      However, nitrate levels from 36 to 88 mg KNO3/kg were also found in those where
      only nitrite was mentioned among the ingredients. A good correlation between
      nitrite and nitrate levels and storage time was shown by multiple linear
      regression analysis. The results obtained were compared with those from
      frankfurters prepared in a pilot plant with different concentrations of NaNO2,
      alone or combined with 200 mg KNO3/kg.

PMID- 9519122
TI  - Measurement of bromate in bread by high performance liquid chromatography with
      post-column flow reactor detection.
AB  - An analytical procedure was developed to measure bromate residues in baked goods
      using a sequence of clean-up procedures followed by high performance liquid
      chromatography (HPLC) with a post-column reaction for oxidants. Deionized water
      was used to extract bromate from bread samples. The extract was treated with a C
      18 solid phase extraction column to remove lipids, a cation exchange column with
      the silver cation to remove chloride, and an ultrafiltration membrane to remove
      proteins. Further treatment of the extract with the sodium form of a
      propylsulphonic acid ion exchange column was necessary to remove the silver that
      leached from the silver column. The method had a detection limit of 3 ng/g in
      baked goods. Recoveries of bromate from breads ranged from 73 to 86% at a
      fortified bromate level of 5-100 ng/g. Pullman-type white bread, produced by a
      sponge and dough method, was prepared in our laboratory for measurement of
      residual bromate. The dough was scaled in three different weights at different
      specific volumes (3.8, 4.1, 4.3), and samples of each of the three weights were
      baked for six different baking times ranging from 24 to 34 min. When bromate at a
      level of 25 mg/kg was added to flour, no residual bromate was detected in any of
      the samples, regardless of weight and baking time.

PMID- 9519123
TI  - Which book? A comparative review of 25 introductory epidemiology textbooks.

PMID- 9519124
TI  - Cochrane Lecture 1997. What evidence do we need for evidence based medicine?
AB  - As presently understood, evidence based medicine aims to advance practice from
      its traditional unverifiable mix of art and science to rational use of measurable
      inputs and outputs. In practice, however, its advocates accept uncritically a
      desocialised definition of science, assume that major clinical decisions are
      taken at the level of secondary specialist rather than primary generalist care,
      and ignore the multiple nature of most clinical problems, as well as the
      complexity of social problems within which clinical problems arise and have to be
      solved. These reductionist assumptions derive from the use of evidence based
      medicine as a tool for managed care in a transactional model for consultations.
      If these assumptions persist, they will strengthen reification of disease and
      promote the episodic output of process regardless of health outcome. We need to
      work within a different paradigm based on development of patients as co-producers
      rather than consumers, promoting continuing output of health gain through shared
      decisions using all relevant evidence, within a broader, socialised definition of
      science. Adoption of this model would require a major social and cultural shift
      for health professionals. This shift has already begun, promoted by changes in
      public attitudes to professional authority, changes in the relation of
      professionals to managers, and pressures for improved effectiveness and
      efficiency which, contrary to received wisdom, seem more likely to endorse
      cooperative than transactional clinical production. Progress on these lines is
      resisted by rapidly growing and extremely powerful economic and political
      interests. Health professionals and strategists have yet to recognise and admit
      the existence of this choice.

PMID- 9519125
TI  - Mortality from venous thromboembolism among young women in Europe: no evidence
      for any effect of third generation oral contraceptives.
AB  - STUDY OBJECTIVE: To investigate whether there has been an increase of venous
      thromboembolism (VTE) mortality in European countries, concurrent with the
      replacement of second generation by third generation combined oral contraceptives
      (COCs). Such an increase has been predicted, and reportedly detected, because
      published studies have detected an increased incidence of VTE associated with
      third generation rather than second generation COC use. DESIGN: Data were
      collected on population and annual VTE mortality in women 15-34 and 35-49 years
      old, and on second and third generation COC sales, from 1981 to 1994 in 13
      European countries. Data from the seven most populous countries were analysed by
      linear regression of annual VTE mortality, in the 15-34 and 15-49 age groups,
      with respect to calculated total and third generation COC use rates, and the
      regression coefficients used to estimate mortality differences between second
      generation users and non-users and between third and second generation users,
      respectively. MAIN RESULTS: The estimated mortality differences in all seven
      countries had confidence intervals wide enough to contain both zero and the
      excess mortalities expected from the results of published studies. This was true
      both for the mortality difference between third and second generation COC users
      and for that between second generation users and COC non-users. CONCLUSIONS:
      Mortality differences of the size expected from the published studies cannot be
      measured using annual national VTE mortality and COC sales data alone, because of
      residual interannual variation in VTE mortality, and possibly confounding between
      rising third generation market share and total COC use.

PMID- 9519127
TI  - Early increases in ischaemic heart disease mortality dissociated from and later
      changes associated with respiratory mortality after cold weather in south east
      England.
AB  - STUDY OBJECTIVE: To identify the time courses and magnitude of ischaemic heart
      (IHD), respiratory (RES), and all cause mortality associated with common 20-30
      day patterns of cold weather in order to assess links between cold exposure and
      mortality. DESIGN: Daily temperatures and daily mortality on successive days
      before and after a reference day were regressed on the temperature of the
      reference day using high pass filtered data in which changes with a cycle length
      < 80 days were unaffected (< 2%), but slower cyclical changes and trends were
      partly or completely suppressed. This provided the short term patterns of both
      temperature and mortality associated with a one day displacement of temperature.
      The results were compared with simple regressions of unfiltered mortality on
      temperature at successive delays. STUDY POPULATION AND SETTING: Population of
      south east England, including London, over 50 years of age from 1976-92. MAIN
      RESULTS: Colder than average days in the linear range 15 to 0 degrees C were
      associated with a "run up" of cold weather for 10-15 days beforehand and a "run
      down" for 10-15 days afterwards. The increases in deaths were maximal at 3 days
      after the peak in cold for IHD, at 12 days for RES, and at 3 days for all cause
      mortality. The increase lasted approximately 40 days after the peak in cold. RES
      deaths were significantly delayed compared with IHD deaths. Excess deaths per
      million associated with these short term temperature displacements were 7.3 for
      IHD, 5.8 for RES, and 24.7 for all cause, per one day fall of 1 degree C. These
      were greater by 52% for IHD, 17% for RES, and 37% for all cause mortality than
      the overall increases in daily mortality per degree C fall, at optimal delays,
      indicated by regressions using unfiltered data. Similar analyses of data at 0 to 
      6.7 degrees C showed an immediate rise in IHD mortality after cold, followed by a
      fall in both IHD and RES mortality rates which peaked 17 and 20 days respectively
      after a peak in cold. CONCLUSION: Twenty to 30 day patterns of cold weather below
      15 degrees C were followed:(1) rapidly by IHD deaths, consistent with known
      thrombogenic and reflex consequences of personal cold exposure; and (2) by
      delayed increases in RES and associated IHD deaths in the range 0 to 15 degrees
      C, which were reversed for a few degrees below 0 degree C, and were probably
      multifactorial in cause. These patterns provide evidence that personal exposure
      to cold has a large role in the excess mortality of winter.

PMID- 9519126
TI  - Low levels of cardiovascular risk factors and coronary heart disease in a UK
      Chinese population.
AB  - OBJECTIVE: To compare the prevalence of cardiovascular risk factors and coronary
      heart disease in Chinese and Europid adults. DESIGN: Population based, cross
      sectional survey. SETTING: Newcastle upon Tyne, UK, 1991-93. SUBJECTS: Altogether
      380 Chinese and 625 Europid adults, aged 25-64 years. MAIN OUTCOME MEASURES:
      Fasting lipid levels, blood pressure, body mass index (BMI), the proportions who
      smoked, and the prevalence of coronary heart disease based on the Rose angina
      questionnaire and major electrocardiographic abnormalities on resting 12 lead
      electrocardiogram (Minnesota codes 1.1-1.2). All figures were age adjusted to the
      1991 England and Wales population. RESULTS: Altogether 183 and 197 Chinese, and
      310 and 315 Europid men and women respectively were seen. Compared with Europid
      men, Chinese men had a lower mean total cholesterol concentration (5.1 versus 5.6
      mmol/l, p < 0.001) and LDL cholesterol (3.2 versus 3.6 mmol/l, p < 0.001); lower
      BMI values (23.8 versus 26.1 kg/m-2, p < 0.001); and smoked less (23% versus 35%,
      p < 0.01)). Compared with Europid women, Chinese women also had lower mean lipid
      levels (total cholesterol: 4.9 versus 5.4 mmol/l p < 0.001, LDL cholesterol: 2.8
      versus 3.1 mmol/l p < 0.001); BMI values (23.5 versus 26.1 kg/m-2, p < 0.001);
      and far fewer were smokers (1.4% versus 33%, p < 0.001). Chinese women, however,
      had higher mean systolic (121 versus 117 mmHg, p > 0.05) and diastolic (75 versus
      68 mmHg, p < 0.001) blood pressures. The prevalence of coronary heart disease was
      significantly lower in Chinese than Europid men (4.9% versus 16.6%, p < 0.001)
      but not significantly different in women (7.3% versus 11.1%, p = 0.16).
      CONCLUSION: Strategies for UK Chinese are needed to maintain this favourable risk
      factor profile and prevent any potential increase in the risk of coronary heart
      disease associated with increasing acculturation.

PMID- 9519128
TI  - Life expectancy in England: variations and trends by gender, health authority,
      and level of deprivation.
AB  - STUDY OBJECTIVES: To investigate variations and trends in life expectancy in
      English district health authorities in relation to gender and Jarman deprivation
      level. DESIGN: Mortality data for English health authorities from 1984-94,
      compiled by the Office for National Statistics, were assessed conventionally and
      using life table techniques. SETTING: District health authorities in England.
      MAIN OUTCOME MEASURES: Life expectancies in the 105 DHAs in relation to rank, to
      gender, and to deprivation category based on the census based Jarman score.
      CONCLUSIONS: Differences in life expectancy had widened over the decade and
      prosperous areas with greatest longevity had seen the largest gains. In most
      deprived areas improvements in life expectancy were negligible. The greatest
      gender differences in life expectancy were also seen in deprived areas.

PMID- 9519130
TI  - Socioeconomic deprivation and health in Glasgow and the west of Scotland--a study
      of cancer incidence among male residents of hostels for the single homeless.
AB  - STUDY OBJECTIVE: To determine the incidence of cancer among homeless men in
      Glasgow. DESIGN: Descriptive study of cancer incidence in a defined, though
      individually unidentifiable, population cohort. SETTING: Glasgow and the West of
      Scotland Region. PARTICIPANTS: Male residents of 10 hostels for the single
      homeless in Glasgow, open for all or part of the period 1975-93. Estimated total
      man-years of risk 21,820. MAIN RESULTS: After adjusting for age and socioeconomic
      deprivation, the proportional incidence ratio (PIR) of tumours of the oral cavity
      and pharynx in hostel residents was over twice what would be expected in the male
      population as a whole (PIR 2.37, 95% CI 1.41, 4.00). Cancers of the oesophagus
      and larynx were also overrepresented (PIR 1.63 and 1.74 respectively). Estimated
      age standardised incidence ratios were greater than would be expected for the
      most socioeconomically deprived areas of the west of Scotland for tumours of the
      oral cavity and pharynx, larynx, oesophagus, and lung (2.39, 1.87, 1.61, and 1.23
      respectively). CONCLUSIONS: The incidence of many cancers is known to be higher
      in lower socioeconomic groups. Within the lowest deprivation category, there is
      evidence from this study for a further excess risk among homeless men for cancers
      of the oral cavity and pharynx, oesophagus, larynx, and lung. Improvements in
      general health care are urgently needed for this particularly vulnerable section
      of the population.

PMID- 9519129
TI  - Widening social inequalities in mortality: the case of Barcelona, a southern
      European city.
AB  - OBJECTIVE: To analyse trends in mortality inequalities in Barcelona between 1983
      and 1994 by comparing rates in those electoral wards with a low socioeconomic
      level and rates in the remaining wards. DESIGN: Mortality trends study. SETTING:
      The city of Barcelona (Spain). SUBJECTS: The study included all deaths among
      residents of the two groups of city wards. Details were obtained from death
      certificates. MAIN OUTCOME MEASURES: Age standardised mortality rates, age
      standardised rates of years of potential life lost, and age specific mortality
      rates in relation to cause of death, sex, and year were computed as well as the
      comparative mortality figure and the ratio of standardised rates of years of
      potential life lost. RESULTS: Rates of premature mortality increased from 5691.2
      years of potential life lost per 100,000 inhabitants aged 1 to 70 years in 1983
      to 7606.2 in 1994 in the low socioeconomic level wards, and from 3731.2 to 4236.9
      in the other wards, showing an increase in inequalities over the 12 years, mostly
      due to AIDS and drug overdose as causes of death. Conversely, cerebrovascular
      disease showed a reduction in inequality over the same period. Overall mortality
      in the 15-44 age group widened the gap between both groups of wards. CONCLUSION:
      AIDS and drug overdose are emerging as the causes of death that are contributing
      to a substantial increase in social inequality in terms of premature mortality,
      an unreported observation in European urban areas.

PMID- 9519131
TI  - Emotional health problems are the most important cause of disability in adults of
      working age: a study in the four counties of the old Oxford region.
AB  - OBJECTIVE: To assess the contribution of emotional health problems to the burden
      of disability affecting people of working age. DESIGN: Analysis of data collected
      in a postal questionnaire survey of a random sample of people aged 18-64 years.
      SETTING: The four counties of the old Oxford region in 1991. SUBJECTS: 9332
      people who responded to a questionnaire survey mailed to 14,000 people randomly
      selected from the Family Health Service Authority registers of the four counties
      of Berkshire, Buckinghamshire, Oxfordshire, and Northamptonshire. OUTCOMES
      MEASURES: Interference with work or other regular daily activity as reported in
      questions 4 and 5 of the health status measure SF-36. RESULTS: In this population
      the prevalence of disability attributable to emotional health problems was
      greater than that attributable to all physical health problems combined. People
      reporting that their work or other regular daily activity was affected by their
      emotional health were much less likely to report a long-standing illness,
      consultation with a GP or consultation with a hospital doctor than people
      reporting a physical health problem. CONCLUSIONS: Emotional health problems are a
      more important cause of disability in adults of working age than all physical
      health problems put together. Their importance is underestimated in health needs
      assessment exercises, which are based on NHS consultation rates or reporting of
      chronic illness. Research into the causes, prevention, and management of
      emotional health problems should be a national priority for the health service.

PMID- 9519132
TI  - Do disease specific characteristics add to the explanation of mobility
      limitations in patients with different chronic diseases? A study in The
      Netherlands.
AB  - STUDY OBJECTIVES: To determine whether disease specific characteristics,
      reflecting clinical disease severity, add to the explanation of mobility
      limitations in patients with specific chronic diseases. DESIGN AND SETTING: Cross
      sectional study of survey data from community dwelling elderly people, aged 55-85
      years, in the Netherlands. PARTICIPANTS AND METHODS: The additional explanation
      of mobility limitations by disease specific characteristics was examined by
      logistic regression analyses on data from 2830 community dwelling elderly people.
      MAIN RESULTS: In the total sample, chronic non-specific lung disease, cardiac
      disease, peripheral atherosclerosis, diabetes mellitus, stroke, arthritis and
      cancer (the index diseases), were all independently associated with mobility
      limitations. Adjusted for age, sex, comorbidity, and medical treatment disease
      specific characteristics that explain the association between disease and
      mobility mostly reflect decreased endurance capacity (shortness of breath and
      disturbed night rest in chronic non-specific lung disease, angina pectoris and
      congestive heart failure in cardiac disease), or are directly related to mobility
      function (stiffness and lower body complaints in arthritis). For atherosclerosis
      and diabetes mellitus, disease specific characteristics did not add to the
      explanation of mobility limitations. CONCLUSIONS: The results provide evidence
      that, to obtain more detailed information about the differential impact of
      chronic diseases on mobility, disease specific characteristics are important to
      take into account.

PMID- 9519133
TI  - Campylobacteriosis in New Zealand: results of a case-control study.
AB  - STUDY OBJECTIVE: To identify and assess the contributions of major risk factors
      for campylobacteriosis in New Zealand. DESIGN: Case-control study. Home
      interviews were conducted over nine months using a standardised questionnaire to
      assess recent food consumption and other exposures. SETTING: Four centres in New
      Zealand with high notification rates of campylobacter infections--Auckland,
      Hamilton, Wellington, and Christchurch. PARTICIPANTS: Case patients were 621
      people notified between 1 June 1994 and 28 February 1995 as having campylobacter
      infection. Control subjects were selected randomly from telephone directories,
      and were matched 1:1 with case patients in relation to sex, age group, and home
      telephone prefix. RESULTS: Risk of campylobacteriosis was strongly associated
      with recent consumption of raw or undercooked chicken (matched odds ratio 4.52,
      95% confidence interval 2.88, 7.10). There was also an increased risk with
      chicken eaten in restaurants (matched odds ratio 3.85; 2.52, 5.88). Recent
      consumption of baked or roasted chicken seemed to be protective.
      Campylobacteriosis was also associated with recent overseas travel, rainwater as
      a source of water at home, consumption of raw dairy products, and contact with
      puppies and cattle, particularly calves. CONCLUSIONS: Improperly cooked chicken
      seems to be associated with a large proportion of campylobacteriosis in New
      Zealand. Thorough cooking of chicken in homes and restaurants could reduce
      considerably the incidence of this disease.

PMID- 9519134
TI  - Epidemiology of hepatitis C virus infection among injecting drug users in
      Australia.
AB  - STUDY OBJECTIVE: To review the epidemiology of hepatitis C virus (HCV) infection
      among injecting drug users (IDUs) in Australia, and consider needs for further
      research and prevention policies and programmes. DESIGN: (1) Review of the
      results of surveillance for HCV; (2) review of published literature on
      prevalence, incidence, and risk factors for HCV among IDUs; and (3)
      reconstruction of incidence rates from prevalence studies of HCV in IDUs. SETTING
      AND PARTICIPANTS: Field and clinic based studies of IDUs in Australia. MAIN
      RESULTS: HCV has been present at high prevalences (of the order of 60-70%) in
      populations of Australian IDUs since at least 1971. Duration of injecting and
      main drug injected were the main predictors of seropositivity, the latter
      possibly a surrogate for frequency of injecting and both together as surrogate
      for cumulative numbers of times injected. Risk of infection begins with first
      injection and continues as long as injecting does. Current incidence is
      approximately 15 per 100 person years, and up to 40 per 100 person years in some
      subpopulations. Incidence may have decreased through the 1980s as a result of
      behaviour change in relation to HIV, as it has for hepatitis B, but not
      significantly so. CONCLUSIONS: Control of HCV infection in Australia will depend
      on effectiveness of measures to control HCV spread among IDUs. This will be a
      greater challenge than the control of HIV in this population has been. Needs
      identified include improved surveillance, especially for recently acquired
      infection, better understanding of exact transmission modes, and urgent
      improvement in prevention strategies.

PMID- 9519135
TI  - Public awareness of malignant melanoma risk factors in Germany.
AB  - STUDY OBJECTIVE: To evaluate the effects of a German public education campaign
      which aimed to improve knowledge on risk factors for malignant melanoma. DESIGN:
      Comparison of data from two successive cross sectional surveys conducted before
      (spring 1993) and after (autumn 1994) the campaign. SETTING: All 56 nursery
      schools in Gottingen, the capital of southern Lower Saxony, Germany.
      PARTICIPANTS: Parents of children attending the nursery schools. Altogether 1341
      questionnaires from parents were included in the first survey (response rate
      64.9%) and 1150 questionnaires in the second survey (response rate 61.4%). MAIN
      RESULTS: The respondents in the second survey were much better at distinguishing
      true melanoma risk factors from false ones. The distribution of scores measuring
      the degree of accurate knowledge about melanoma risks indicated that this had
      improved significantly (p < 0.001). The most pronounced change with regard to
      knowledge of single risk factors could be observed for "sunburn during
      childhood," which was correctly identified by 63.1% in the first survey and by
      85.6% in the second. Substantial improvement in accurate knowledge about the
      influence of constitutional skin factors--number of naevi, skin type etc--was
      also found. CONCLUSIONS: Notwithstanding the methodological problems in this
      analysis (non-randomised design, only before and after comparison, no control
      group, number of non-respondents), it is concluded that this campaign improved
      understanding of the risks of melanoma. Continuing public education activities
      should be implemented to sustain and improve further knowledge on prevention of
      malignant melanoma.

PMID- 9519136
TI  - Conservatively managed tibial shaft fractures in Nottingham, UK: are pain,
      osteoarthritis, and disability long-term complications?
AB  - OBJECTIVES: To investigate longterm pain and disability subsequent to a tibial
      shaft fracture treated conservatively. DESIGN AND SETTING: Subjects who had
      sustained a tibial shaft fracture more than 27 years ago were compared with those
      who had not. SUBJECTS: 572 fracture patients (identified from the records of the
      plaster room) aged over 16 at the time of injury were contracted and were
      compared with 2285 randomly selected subjects matched for age, sex, and general
      practice. MAIN OUTCOME MEASURES: Self reported knee pain; self reported GP's
      diagnosis of osteoarthritis; ability to climb stairs, walk 100 yards, to bend,
      kneel, or stoop; and SF-36 physical functioning score. RESULTS: Subjects were
      reviewed between 27 and 41 years after tibial shaft fracture (mean 35 years).
      Fracture patients were more likely to suffer chronic knee pain (odds ratio 1.23;
      95% confidence interval (CI) 1.00, 1.51) and report being given a diagnosis of
      osteoarthritis by their GP (odds ratio 1.46; 95% CI 1.08, 1.97). The ability to
      climb stairs, walk 100 yards, and bend, kneel, or stoop was less in the fracture
      group than the other subjects. The SF-36 physical function score was
      significantly lower in the fracture group. CONCLUSIONS: More than 27 years after
      a tibial shaft fracture, subjects have more knee pain than the rest of the
      population. They also have greater difficulty performing everyday physical
      activities. The excess morbidity may be due to injury factors or treatment
      factors, and further research is needed to investigate this important association
      further.

PMID- 9519137
TI  - Distressed or relieved? Psychological side effects of breast cancer screening in
      The Netherlands.
AB  - STUDY OBJECTIVES: To assess the psychological impact of mammographic screening on
      women with non-malignant outcomes after attending the Netherlands' National
      Breast Cancer Screening Programme. DESIGN: During one year all women with false
      positive test results (95) in a screening area were invited for the study. Each
      false positive was matched with two women with normal mammograms with respect to
      age and municipality. A random reference group of 400 was drawn from the female
      population in an area not yet included in the screening programme. Experiences
      with screening and psychological status of subjects were assessed 8-10 weeks
      after screening (T1) and again after six months (T2), by interviews as well as
      questionnaires. References completed two questionnaires with a six months'
      interval. PARTICIPANTS: 74 (78%) women with false positive outcomes and 113 (59%)
      women with negative outcomes participated at T1, of these 65 (88%) and 105 (93%)
      at T2, respectively; 238 references returned questionnaires at T1 (59%), of these
      143 (60%) at T2. MAIN RESULTS: At 8-10 weeks after the screening, the women who
      received false positive test results scored higher on most of the variables
      indicating psychological disfunctioning than women with normal mammograms, but
      did not notably differ on the same variables from the non-screened reference
      group. Women with normal mammograms had the lowest scores on all the variables in
      the study at both assessments. The same situation was observed six months later.
      Although 61% of the women who received false positive mammograms reported that
      they had experienced the "false alarm" as a stressful event, this experience had
      apparently no adverse effects on their psychological functioning, as assessed 8
      10 weeks after screening. CONCLUSIONS: Overall, breast screening is not likely to
      generate adverse psychological effects in "healthy" women, even if the outcome is
      false positive. Differences in psychological functioning between false positives
      and negatives are more likely ascribable to feelings of relief in the negative
      group than to raised anxiety and distress in the false positive group.

PMID- 9519138
TI  - Pure tone audiometry and impedance screening of school entrant children by
      nurses: evaluation in a practical setting.
AB  - BACKGROUND: Screening for hearing loss in English children at entry to school
      (age 5-6 years) is usually by pure tone audiometry sweep undertaken by school
      nurses. This study aimed to compare the validity and screening rates of pure tone
      audiometry with impedance screening in these children. METHODS: Two stage pure
      tone audiometry and impedance methods of screening were compared in 610 school
      entry children from 19 infant schools in north east England. Both procedures were
      completed by school nurses. The results of screening were validated against
      subsequent clinical assessment, including otological examination and actions
      taken by an independent assessor. RESULTS: Both methods produced broadly similar
      validation indices after two stages of screening: sensitivity was 74.4% for both
      methods; specificity was 92.1% and 90.0%; and predicted values of a positive test
      43.2% and 37.6% respectively for pure tone audiometry and impedance methods.
      Single stage screening in both methods produced higher sensitivity but lower
      specificity and predictive values of a positive test than two stage screening.
      Screening rates were appreciably higher with impedance methods than with pure
      tone audiometry. CONCLUSIONS: In choosing the method to be used, it must be borne
      in mind that the impedance method is technically more efficient but takes longer
      than pure tone audiometry screening. However, the latter method allows
      opportunity for other health inquiries in these children.

PMID- 9519139
TI  - Behavioural dynamics of a clinical trial of sunscreens for reducing solar
      keratoses in Victoria, Australia.
AB  - OBJECTIVE: To determine whether the behaviour of participants based on perception
      of treatment group in a randomised trial contributed to clinical outcome. DESIGN:
      A double blind randomised controlled trial of the effect of daily application of
      SPF 17 broad spectrum sunscreen cream (or placebo) on solar keratoses. SETTING: A
      rural city in Victoria, Australia. Residents aged 40 years or over were invited
      by letter to attend for a skin cancer screening check. Of these, 588 people with
      between one and 30 solar keratoses enrolled in the trial and 431 completed the
      trial, which extended over a six month period that included summer. Participants'
      perceptions of their treatment allocation, adherence with the treatment regimen,
      adoption of other sun protection behaviours, side effects, and perceptions of
      change in condition were measured at two monthly intervals. RESULTS: There were
      no significant differences between those who completed the study and those that
      did not for sex, age, treatment group, skin type, number of solar keratoses or
      correct perception of treatment group. Thirty per cent of those completing the
      study correctly guessed their treatment allocation, and people were just as
      likely to be right as to be wrong when they stated their opinion about their
      treatment allocation (z = 1.04; p = 0.15). Study group, skin type, amount of time
      spent outdoors, presence of side effects, perceptions of change in skin condition
      did not significantly predict correct perception of treatment allocation.
      Multivariate analysis of variance indicated that adoption of other sun protection
      and adherence with cream use were not significantly affected by actual treatment
      allocation, correct perception of treatment allocation nor by their interaction.
      Poisson regression analysis showed a significantly lower difference ratio of
      solar keratoses in the sunscreen group compared with the placebo base cream group
      (OR 0.55; CI = 0.46, 0.64), and for women compared with men (OR = 0.76; CI =
      0.63, 0.93) but no independent effect of any of the indices of other sun
      protection or adherence. CONCLUSIONS: A sufficient level of commitment to study
      procedures was achieved, so that trial participants did not adopt other
      behaviours that affected treatment outcomes. It is recommended that the potential
      threat to validity posed by the behaviour of participants be recognised at an
      early stage in planning of clinical trials, so that strategies to deal with this
      can be integrated into study protocols.

PMID- 9519140
TI  - Population predictors of community health and social service use in Northern
      Ireland.
AB  - STUDY OBJECTIVE: To investigate the characteristics of elderly populations
      associated with variations in their use of community health and personal social
      services and to test the hypotheses that the variations are related to: (a) the
      age structure of an elderly population; (b) the population's socioeconomic
      composition, including the level of deprivation; and (c) household or living
      arrangements. DESIGN: A common file of 1991 population census and 1994 NHS
      community trust operational variables was constructed for 67 postcode sectors,
      with the independent variables describing the age-sex groups to be studied. Clear
      criteria for the exclusion of "empty" sectors were developed. Relationships using
      bivariate and multivariate correlation and stepwise multiple regression were
      explored. SETTING: Eastern Health and Social Services Board area, Northern
      Ireland (Belfast and hinterland). PARTICIPANTS: Population of statutory
      pensionable age; in aggregate, younger and older age bands. MAIN RESULTS: The age
      structure or mean age of the elderly population had only a weak association with
      the community health and social service client rate, but there were strong
      associations with socio-economic variables, particularly the percentage of those
      living alone who were without a car and the percentage of pensioner households
      that included an adult of below pensionable age. Parsimonious multiple regression
      models accounted for between 46% and 80% of the variation in the NHS community
      trust client rate. Greater explanations were achieved for the young elderly
      population than for those aged 75+ years and, when the population was divided
      between young and old age bands, for men than for women. CONCLUSIONS: Community
      health and social services for elderly people in eastern Northern Ireland were
      focused on those with a low income and those who were not co-resident with adults
      of working age. When local elderly populations are compared, per capita morbidity
      and dependency are often higher where the mean age is low, and vice versa,
      because of the inverse relationship between socioeconomic status and survival in
      old age. Capitation scales for resource allocation with positive age weighting
      will be of little use if no account is taken of the relative prevalence of need
      in the youngest or base age group.

PMID- 9519141
TI  - Quantitative estimates of sensitivity and specificity in mammographic screening.

PMID- 9519142
TI  - Paracetamol in suicide and non-accidental overdose--are restrictions justified?

PMID- 9519143
TI  - Characterization of submicron systems via optical methods.
AB  - As a means of addressing the issues of drug delivery, submicron colloidal systems
      have become increasingly used as pharmaceutical formulations. Accurately
      characterizing physical properties of the constituent particulates present in
      these systems is an indispensable activity. However, measuring descriptors such
      as particle size distribution and surface potential presents an experimental
      challenge. This paper describes the physical basis for a number of optically
      based techniques that are useful in this task. In addition, the caveats and
      benefits of these methods are discussed and reference is made to their use in the
      examination of various multiphase systems such as liposomes, nanoparticles, and
      emulsions.

PMID- 9519144
TI  - Analysis of plasmid DNA from a pharmaceutical perspective.
AB  - The advent of gene therapy and polynucleotide-based vaccines has resulted in the
      use of plasmid DNA as a drug substance. Although biologically (cell or animal)
      based assays must currently be employed to establish the identity and potency of
      such drugs, we argue that in the future, a combination of microchip-based
      mutation detection devices combined with an array of chromatographic,
      electrophoretic, hydrodynamic, and spectroscopic methods can be employed to
      rigorously establish these properties. We review a variety of such methods in
      this context and also consider the issue of the chemical stability of plasmids.
      Extensive comparison is made to protein-based pharmaceuticals with the unique
      importance of polynucleotide sequence emphasized in comparison to protein
      tertiary structure.

PMID- 9519145
TI  - Effect of high molecular mobility of poly(vinyl alcohol) on protein stability of
      lyophilized gamma-globulin formulations.
AB  - The protein stability of lyophilized serum gamma-globulin (BGG) formulations
      containing poly(vinyl alcohol) (PVA) and dextran was studied in relation to the
      molecular mobility as determined by proton NMR. The critical temperature, Tmc, at
      which the Lorentzian relaxation process due to liquid polymer protons appears in
      these lyophilized formulations was lower than the glass transition temperature,
      Tg. Above Tmc, protein aggregation in the formulations was related to the Tmc
      according to the Williams-Landel-Ferry equation by replacing Tg with Tmc. Protein
      aggregation appears to occur substantially in a "rubbery-like" state even below
      Tg, if the formulations become microscopically liquidized above Tmc. Lyophilized
      BGG formulations containing PVA with a lower water content were less stable than
      those containing dextran with a higher water content. The difference in stability
      can be explained by the difference in the Tmc of these formulations. Tmc that is
      determined by NMR relaxation measurement appears to be a useful parameter for the
      characterization of protein formulations, for which the Tg cannot generally be
      determined by standard calorimetric techniques. Furthermore, Tmc appears to be
      more closely related to protein stability than does Tg.

PMID- 9519146
TI  - Spray-drying of air-liquid interface sensitive recombinant human growth hormone.
AB  - Spray-drying is an attractive method for preparing fine recombinant human growth
      hormone (rhGH) powders if the detrimental effect of protein degradation at the
      air-liquid interface on the protein can be minimized. In this study, we
      demonstrated that rhGH degradation (insoluble and soluble aggregate formation),
      as the consequence of air-liquid interfacial degradation, could be prevented
      using the appropriate formulation. Adding polysorbate-20 surfactant into the
      liquid feed (with no presence of sugar protectant) significantly reduced the
      formation of insoluble protein aggregates, while adding the divalent metal zinc
      ion effectively suppressed the formation of soluble protein aggregates. The
      combination of the two yielded a spray-dried rhGH powder having insignificant
      protein degradation. Our data suggest that the two components might protect the
      protein through different mechanisms. Polysorbate molecules occupy the air-liquid
      interface of spray droplets, thereby reducing the chance for rhGH to form
      insoluble aggregates by surface denaturation. Two zinc ions associate with two
      rhGH molecules to form a dimer complex that can resist the formation of soluble
      protein aggregates. Characterization of spray-dried powders by scanning electron
      microscopy suggests that both formulation and drying conditions have a strong
      influence on particle morphology and shape. Overall, spherical rhGH powders of
      smooth surface and good biochemical quality can be prepared by spray-drying using
      this formulation with no addition of sugar protectant.

PMID- 9519147
TI  - Remarkable increase in nuclease resistance of plasmid DNA through supramolecular
      assembly with poly(ethylene glycol)-poly(L-lysine) block copolymer.
AB  - Supramolecular associates of DNA with Poly(ethylene glycol)-poly(L-lysine) block
      copolymers (PEG-PLL) were prepared in aqueous milieu, and the water solubility
      under charge-neutralized (stoichiometric) conditions was maintained. Associates
      thus prepared achieved remarkable resistance against nuclease attack, probably
      due to the formation of PEG palisade surrounding the ion-complexed core of the
      DNA with the PLL segment of the block copolymer. Further, to estimate the
      stability of the associate, the rate of interexchange reaction of DNA in the
      associate with poly(vinyl sulfonate) was evaluated from a method using a
      metachromasy of toluidine blue dye. Of interest, the nuclease resistance of DNA
      in PEG-PLL/DNA associate had an inverse correlation with the rate of
      interexchange reaction and, thus, progressively increased with an increase in the
      molecular weight of PLL segment in the block copolymer, indicating the
      substantial importance of block copolymer design for DNA stabilization.

PMID- 9519148
TI  - Lipid-based delivery systems for improving the bioavailability and lymphatic
      transport of a poorly water-soluble LTB4 inhibitor.
AB  - Ontazolast is a potent inhibitor (IC50 = 1 nm) of calcium ionophore A23187
      stimulated leukotriene B4 (LTB4) biosynthesis in human peripheral blood
      leukocytes. The compound is practically insoluble in water (0.14 microgram/mL)
      and previous studies in animals have demonstrated extensive presystemic drug
      clearance through hepatic first-pass metabolism. Bioavailability of a suspension
      formulation in rats was less than 1%, but increased to approximately 9% when
      administered as a 20% soybean oil-in-water emulsion. The emulsion formulation and
      three additional lipid-based formulations were administered by gavage to
      conscious, minimally restrained rats in a novel, double-cannulated model to
      determine the effects of formulation on systemic blood absorption and mesenteric
      lymph transport of ontazolast. The bioavailability of ontazolast was
      significantly and substantially enhanced by all of the lipid-based formulations.
      While these formulations also significantly increased the amount of ontazolast
      transported by the lymph, the total amounts transported were insufficient to
      account for the improvement in bioavailability, which may be due to the
      elimination or reduction of the barriers of poor aqueous solubility and slow
      dissolution to absorption of ontazolast from the gastrointestinal tract, or the
      effects of lipid on the gastrointestinal membrane permeability, transit time, or
      metabolism of ontazolast. Semisolid SEDDS formulations, composed of Peceol and
      Gelucire 44/14, produced bioavailability similar to the emulsion formulation. The
      total amount of ontazolast transported by the lymph varied directly with the
      amount of concurrent triglyceride transport and appeared to be favored by
      formulations that prolong gastric emptying time or promote rapid absorption of
      ontazolast from the gastrointestinal tract.

PMID- 9519150
TI  - Myocardial effect compartment modeling of metoprolol and sotalol: importance of
      myocardial subsite drug concentration.
AB  - We have recently reported the time course of acute myocardial drug uptake and
      simultaneous pharmacodynamic effects for metoprolol (4 mg; n = 12) and sotalol
      (20 mg; n = 10) in patients with ischemic heart disease. The acute
      pharmacodynamic effects of the two drugs included reductions in both spontaneous
      heart rate and the contractile index peak positive rate of left ventricular
      pressure rise and prolongation of the electrocardiographic PR interval, all of
      which exhibited an equilibration delay compared with myocardial drug content. The
      objective of the current study was to analyze the relationship between myocardial
      drug content and effect for both metoprolol and sotalol using an effect
      compartment model, to examine the potential for the two drugs to share a common
      subsite of action in the myocardium. The time course of myocardial drug content
      was best described by a one-compartment model for metoprolol and a two
      compartment model for sotalol. A linear pharmacodynamic model, relating the
      amount of drug at the effect-site (Ae) with each of the three effects, was used
      in the effect compartment modeling. The slope of each of these effects as a
      function of Ae was considerably flatter for sotalol than for metoprolol,
      reflecting the relative beta-adrenoceptor antagonistic potencies of the two
      drugs. The exit rate constant from the effect compartment (K(eo)) did not differ
      significantly from each other or from the exit rate constant from the
      "peripheral" compartment (K21) for sotalol. The results suggest that the effect
      compartment within the myocardium for both drugs may correspond to a "peripheral"
      compartment, even though a "peripheral" pharmacokinetic compartment for
      myocardial metoprolol content was not apparent. Thus, the effect compartment for
      many cardioactive drugs may correspond to a pharmacokinetically "peripheral"
      compartment, irrespective of localization of effect to a small (e.g. sinoatrial
      node) or large (e.g. ventricular myocardium) region of the heart.

PMID- 9519149
TI  - Preparation and characterization of a cocrystalline suspension of [LysB28,ProB29]
      human insulin analogue.
AB  - Soluble preparations of [LysB28,ProB29]-human insulin analogue (LysPro) exhibit
      more rapid absorption than human insulin upon subcutaneous injection. Biphasic
      mixtures of LysPro and intermediate-acting insulin suspensions could provide
      advantages over current preparations for the treatment of diabetes. To prepare
      biphasic mixtures of LysPro, a suspension formulation of the analogue is
      required. We have devised a method for crystallizing LysPro with the basic
      peptide protamine yielding neutral protamine LysPro (NPL) suspension. The
      crystallization conditions are strongly dependent on the precipitation procedure
      and temperature. Using various techniques, the crystalline and suspension
      characteristics of NPL are found to be similar to human insulin (neutral
      protamine Hagedorn, NPH) (8:1 molar ratio insulin:protamine, rod-shaped crystals,
      particle size of 4.0-6.0 microns, and Point of Zero Charge at 6.0-7.0). Using a
      dog model with NPL or NPH injected subcutaneously and glucose levels clamped at
      basal, NPL was found to have kinetic and dynamic responses analogous to human
      insulin NPH [Cmax (maximal insulin or LysPro concentration, ng/mL) of 2.61 +/-
      0.22, NPL; 2.58 +/- 0.36, NPH, attained at Tmax (min) of 93 +/- 22, NPL; 145 +/-
      33 NPH, and Rmax (maximal rate of glucose infusion, mg/kg min) of 10.8 +/- 1.2,
      NPL; 13.2 +/- 1.9, NPH, attained at TRmax (min) of 277 +/- 58, NPL; 265 +/- 38,
      NPH]. There are no statistically significant differences between the insulin
      curves or the glucose responses. These results provide insight into the mechanism
      of action of NPH suspensions and the relationship to duration of action.
      Furthermore, the formulation of a suspension of LysPro having an intermediate
      time-action makes possible the preparation of stable biphasic mixtures containing
      LysPro and NPL.

PMID- 9519151
TI  - Consideration of conformational transitions and racemization during process
      development of recombinant glucagon-like peptide-1.
AB  - Physicochemical characterization of dry, excipient-free recombinant glucagon-like
      peptide-1 (rGLP-1) indicates the conformation and purity of the bulk peptide is
      dependent on the purification scheme and the in-process storage and handling. The
      recombinant peptide preparations were highly pure and consistent with the
      expected primary structure and bioactivity. However, variations in solubility
      were observed for preparations processed by different methods. The differences in
      solubility were shown to be due to conformational differences induced during
      purification. A processing scheme was identified to produce rGLP-1 in its native,
      soluble form, which exhibits FT-IR spectra, consistent with glucagon-like peptide
      1 synthesized by solid-state peptide synthesis. rGLP-1 was also found to undergo
      base-catalyzed amino acid racemization. Racemization can impact the yield and
      impurity profile of bulk rGLP-1, since the peptide is exposed to alkali during
      its purification. A combination of enzymatic digestion using leucine
      aminopeptidase (which cleaves N-terminal L-amino acids >> D-amino acids) and
      matrix-assisted laser desorption ionization mass spectrometry was used to
      identify racemization as a degradation pathway. The racemization rate increased
      with increasing temperature and base concentration, but decreased with increasing
      peptide concentration. The racemized peptides were shown to be less bioactive
      than rGLP-1.

PMID- 9519152
TI  - Conformational analysis of the anhydrotetracycline molecule: a toxic
      decomposition product of tetracycline.
AB  - Anhydrotetracycline (AHTC) is a toxic decomposition product of the widely used
      antibiotic tetracycline (TC). The side effects of AHTC have been attributed to
      the conformational changes in the ring system. In the present study a systematic
      conformational analysis has been carried out using the semiempirical quantum
      mechanical AM1 model. The conformational pH dependence has been analyzed through
      the study of all the ionized species. The results obtained showed two distinct
      families of conformation, referred to as A and B, with the interconversion
      process involving a rotation around the C4a-C12a bond. The solvent effect has
      been considered using the continuum model COSMO. From the population analysis in
      the gas phase, we conclude that form A should be dominant for the LH3+ and LH2 +/
      species and B is the preferred conformer for the L2- ionized form (97.54%). For
      the LH- derivative, we predict that both conformations should be present in the
      equilibrium mixture in the gas phase, with the relative concentration found to be
      68.47% (A) and 31.53% (B). The inclusion of the solvent does not change the A/B
      equilibrium for the LH3+ and LH2 +/- species. However, for the LH- form, the
      equilibrium is shifted to conformer A in water solution. The population analysis
      in water solution for the L2- suggest the following relative concentrations: A
      (34.46%) and B (65.54%). The biological activity of the TC parent compound is
      attributed to the zwitterionic species, which should adopt a twisted
      conformation. According to the results obtained in the present study, the most
      abundant form of the LH2 +/- zwitterionic species for the AHTC molecule is the
      extended one (100% in both the gas phase and water solution). Therefore, from a
      pharmacodynamic point of view, this conformational difference should be taken
      into account in order to explain the toxic effects of the anhydrous derivative.
      Another point related to the structure-activity relationship was analyzed through
      the investigation of the tautomerization process LH2(0)-->LH2 +/-. The result
      obtained suggests that the LH2(0) tautomer should be dominant in the gas phase
      (nonpolar solvent) and adopt a conformation classified as B. In water solution,
      the tautomer LH2 +/- is present as conformer A (96%). This result is in agreement
      with the conformation changes involved in the tautomerization process for the OTC
      active derivative.

PMID- 9519153
TI  - Evaluation of in vitro precipitation methods.
AB  - Four in vitro precipitation methods were tested and evaluated using flavopiridol
      and diazepam formulations. The methods include static serial dilution, dynamic
      injection, and dropwise addition with and without stirring. The results generated
      from these methods are comparable and complementary. The static serial dilution
      method is most effective in quantifying the amount of precipitation and more
      descriptive of the formation and redissolution of the precipitate than the
      others. The dynamic injection method, however, has its merit in more
      realistically simulating the physiological environment of drug-blood interaction
      near the injection sites.

PMID- 9519154
TI  - Triglyceride-based microemulsion for intravenous administration of sparingly
      soluble substances.
AB  - A pharmaceutically acceptable microemulsion system composed of a medium-chain
      triglyceride (MCT), soybean phosphatidylcholine and poly(ethylene glycol)(660)-12
      hydroxystearate (12-HSA-EO15) as amphiphiles, and poly(ethylene glycol) 400 (PEG
      400) and ethanol as cosolvents is presented and characterized in terms of phase
      behavior, microstructure, solubilization capacity and in vivo effects after
      intravenous administration to conscious rats. At a total concentration of 11.9 wt
      % of soybean phosphatidylcholine and 12-HSA-EO15, a microemulsion region was
      formed over a wide range of alpha, where alpha is the weight fraction of MCT/(MCT
      + water + PEG 400 + ethanol). The microstructure of the microemulsion was of a
      bicontinuous nature even at high oil concentrations. The mean droplet diameter of
      the oil-in-water emulsion formed after dilution of microemulsions prepared at
      different alpha within the one-phase region was between 60 and 200 nm. It was
      concluded that it is possible to administer up to 0.5 mL/kg of the microemulsion
      (alpha = 0.5) without producing any significant effect on acid-base balance,
      blood gases, plasma electrolytes, mean arterial blood pressure (MAP), heart rate
      (HR), and PQ time (the time between depolarization of atrium and chamber). At a
      dose of 1.5 mL/kg, a temporary increase in MAP, a decrease in HR, and a
      prolongation of the PQ time were observed.

PMID- 9519155
TI  - Influence of the permeation enhancers 1-alkyl-2-pyrrolidones on permeant
      partitioning into the stratum corneum.
AB  - In a previous study, the enhancing effects of a series of 1-alkyl-2-pyrrolidones
      (APs; 1-ethyl, 1-butyl, 1-hexyl, and 1-octyl-2-pyrrolidone) on the transport of
      steroidal permeants across hairless mouse skin were investigated via a parallel
      pathway skin model. Isoenhancement concentration conditions were deduced under
      which different APs induce essentially the same transport enhancement for the
      lipoidal pathway of the stratum corneum (s.c.). As a continuing effort to
      understand the mechanism of action of permeation enhancers, the influence of the
      APs on permeant partitioning into hairless mouse s.c. was investigated under the
      isoenhancement concentration conditions using beta-estradiol (E2 beta) as the
      model permeant. The amount of E2 beta uptake into s.c. was found to be
      essentially the same for all the APs under these isoenhancement conditions. This
      result suggests that inducing a higher partitioning tendency for E2 beta into the
      lipoidal pathway of hairless mouse s.c. is a principal mechanism of action of the
      APs in enhancing transdermal transport. The uptake of the APs into s.c. lipoidal
      domains was also determined, and the results show only a modest (approximately 2
      fold) increase in the uptake of the APs in going from 1-ethyl-to 1-octyl-2
      pyrrolidone under isoenhancement conditions. This indicates the potency of the
      APs as permeation enhancers is only very modestly dependent upon the alkyl chain
      length in this chain length region when compared at concentrations in the
      microenvironment where the action occurs in the lipid domains.

PMID- 9519156
TI  - Plasma protein binding of gyrase inhibitors.
AB  - Plasma protein binding of a wide range of gyrase inhibitors in clinical practice
      or trials has been determined by ultrafiltration to determine structure-protein
      binding relationships. The protein binding was independent of overall
      lipophilicity. In particular, the "western" part of the "quinolone" skeleton,
      consisting of a heterocyclus at position 7 and varying substituents at position
      8, strongly influences the extent of protein binding, indicating that this part
      interacts with the plasma protein. In contrast, substituents in position N1 do
      not show an effect on the protein binding in this series of compounds.

PMID- 9519157
TI  - Preclinical assessment of immunoreactivity of a new purified equine F(ab')2
      against European viper venom.
AB  - The immunological and pharmacokinetic properties of a new, further purified,
      pasteurized preparation of equine F(ab')2 (VIPERFAV) against Vipera aspis, Vipera
      berus, and Vipera ammodytes venom were compared with the current equine F(ab')2
      preparation (IPSER Europe). Affinity constants of the V. aspis-specific F(ab')2
      were determined using biosensor technology and found to be in the range of 10(8)
      M-1 for the four antigenic fractions of V. aspis toxins and for both F(ab')2
      preparations. The improvement of 51% in the specific activity (LD50 mg-1) of the
      new F(ab')2 was in close agreement with the 1.8-fold increase in the
      immunoreactive fraction of the new preparation. In vivo investigations of venom
      immunocomplexation by F(ab')2 in rabbits confirmed the ability of F(ab')2 to
      neutralize and redistribute toxin venom. Infusion of a stoichiometric molar ratio
      (i.e., 1 mg kg-1) of the new antivenom induced a 2.3-fold elevation of the plasma
      venom concentration with a Tmax observed 8 h after F(ab')2 administration and a
      decline in the terminal half-life from 31.92 +/- 4.49 h to 16.73 +/- 4.34 h, in
      contrast, for the venom alone. The area under the curve was 1.4-fold greater in
      the VIPERFAV group than in the IPSER Europe group during the post-F(ab')2
      infusion period. Increasing the F(ab')2 dose to 3 mg kg-1 increased by 27% the
      percent of venom bound to F(ab')2. Finally, the greater the venom distribution,
      the smaller and less pronounced the plasma redistribution. These results
      demonstrate that the purification and pasteurization steps involved in the
      preparation of the new F(ab')2 have no deleterious influence on F(ab')2 affinity
      but, on the contrary, improve the protective efficacy. Alteration of viper venom
      kinetics by specific F(ab')2 antivenom was also shown to be dependent on the
      interval between of F(ab')2 administration and venom bite and on the specific
      F(ab')2 dose administered.

PMID- 9519158
TI  - In vitro evaluation of pluronic F127-based controlled-release ocular delivery
      systems for pilocarpine.
AB  - The overall objective of this study was to develop pluronic F127 (PF127)
      containing formulations of pilocarpine hydrochloride (PHCL) suitable for
      controlled-release ocular delivery of PHCL. Various aqueous formulations were
      evaluated containing 1% w/v PHCL and 25% w/v PF127 alone or with one of the
      following additives present: poly(ethylene glycol) 4600 (PEG),
      poly(vinylpyrrolidone) 10,000 (PVP), poly(vinyl alcohol) 10,000 (PVA),
      methylcellulose 15 cP (MC), and hydroxypropyl methylcellulose 80-120 cP (HPMC).
      The in vitro dissolution of the PF127 formulations and the pilocarpine release
      profiles from them were obtained simultaneously at 34 degrees C and room
      temperature using a membraneless in vitro model. It was observed that the PEG-
      and PVP-containing PF127 formulations of PHCL dissolved the quickest and released
      the drug at a significantly faster rate than the control PF127 formulation, which
      had no additive present. The PF127 formulations of PHCL containing MC or HPMC
      exhibited the slowest dissolution rates and released the drug the slowest. The
      same rank order was observed at each temperature for the dissolution and PHCL
      release profiles of each formulation. On the basis of the in vitro results, the
      PF127 formulations of PHCL containing MC or HPMC as an additive showed potential
      for use as controlled-release ocular delivery systems for PHCL.

PMID- 9519159
TI  - Thermal analysis of freeze-dried liposome-carbohydrate mixtures with modulated
      temperature differential scanning calorimetry.
AB  - In this study we investigated the use of modulated temperature differential
      scanning calorimetry (MTDSC) for the detection of the glass transition
      temperature (Tg) in freeze-dried cakes of lyoprotected liposomes and for the
      analysis of frozen carbohydrate solutions. The glass transition appeared in the
      reversing heat flow, whereas the bilayer melting endotherm was observed in the
      nonreversing heat flow. This enabled the detection of Tg even in samples were the
      glass and bilayer transition overlapped. In addition, relaxation processes
      occurring in nonannealed freeze-dried carbohydrate-liposome mixtures, which
      hinder the determination of Tg with conventional DSC, were also separated from
      the heat capacity related heat flow. Analysis of frozen carbohydrate solutions
      with MTDSC facilitated the identification of the glass transition,
      devitrification peak, and "softening" transition, which could help to further
      optimize freeze-drying conditions by rationale. Sampling and selection of
      experimental parameters are discussed for the special case of porous, freeze
      dried cakes.

PMID- 9519160
TI  - Microscale titrimetric and spectrophotometric methods for determination of
      ionization constants and partition coefficients of new drug candidates.
AB  - This study describes the adaptation of conventional titrimetric and
      spectrophotometric techniques to a microscale for the determination of drug
      ionization constants (pKa) and partition coefficients (log P). The apparatus for
      determining pKa and compound purity (or equivalent weight) consists of a three
      port conical glass microvial maintained at 25 degrees C, a pH microelectrode, and
      a microinjection pump equipped with a 10 microL gastight syringe for titrant
      delivery. Sample mixing and protection from atmospheric CO2, which is
      particularly important at the microscale, is accomplished using a fine stream of
      water-saturated N2 bubbles. Simple titrimetric procedures combined with ionic
      equilibria models which allow the accurate determination of pKa and purity (or
      equivalent weight) using sample sizes in the microgram range and solution volumes
      of 10-100 microL were developed and validated using acetic acid and tromethamine.
      Simultaneous determinations of pKa, purity or equivalent weight, and
      octanol/water partition coefficient were shown to be possible from a single
      sample of a test solute by adapting the pH-metric technique to a microscale.
      Using benzoic acid as a model compound, a pKa of 4.24 and octanol/water partition
      coefficient of 64 were obtained, in close agreement with the literature values.
      The principles employed in titrimetric analysis were also applied to demonstrate
      the spectrophotometric determination of benzoic acid's pKa and partition
      coefficient using only 6 micrograms of compound. The microscale titration method
      was then used to determine the two pKa values of an "unknown" diprotic acid
      containing a carboxyl and an aromatic SH group. The phenyl thiol pKa was
      confirmed using the microscale spectrophotometric procedure.

PMID- 9519161
TI  - Surface modification of polyanhydride microspheres.

PMID- 9519162
TI  - Effects of ethanol and dexamethasone on epidermis examined by in vitro 31P
      magnetic resonance spectroscopy.

PMID- 9519163
TI  - Effect of altered serum lipid concentrations on the IC50 of halofantrine against
      Plasmodium falciparum.
AB  - Halofantrine (Hf) is a highly lipophilic antimalarial which significantly
      associates with triglyceride (TG) rich plasma lipoproteins, and this is likely
      manifest as a decrease in the free fraction of drug. This study assessed the
      effect of using growth media containing 10% serum containing different
      concentrations of TG (i.e. TG-rich plasma lipoproteins) on the IC50 of Hf
      determined using continuous in vitro culture of Plasmodium falciparum. Serum was
      collected from a human subject in either a fasted state or at various times after
      ingestion of a fatty meal. There was a linear and statistically significant 2.5
      fold increase in the IC50 of Hf across a 6-fold range of increasing TG
      concentrations, with the increased IC50 values being ascribed to a decreased free
      fraction of Hf in the growth media due to sequestration by TG-rich lipoproteins.
      Chloroquine diphosphate, which is hydrophilic and not significantly bound by TG
      rich lipoproteins, was used as a control and its IC50 values were independent of
      TG concentrations. These data indicate that consideration should be given to the
      adoption of standard conditions for the collection of serum with respect to pre-
      or postprandial states, and that subject- and disease-related factors which alter
      plasma lipoprotein profiles should be considered when interpreting the IC50
      profile of Hf (and possibly other lipophilic antimalarials). Furthermore,
      although food is known to affect the pharmacokinetics of Hf, these data suggest
      that altered plasma lipoprotein profiles could also influence its pharmacodynamic
      profile.

PMID- 9519164
TI  - Calman-Hine: two years on.

PMID- 9519165
TI  - Launching a palliative care homepage: the Edmonton experience.
AB  - The Internet, with its graphical subdivision, the World Wide Web (WWW). has
      become a powerful tool for the dissemination of information and for
      communication. This paper discusses the authors' experiences with creating,
      launching and maintaining an official publication on the Internet by the Edmonton
      Regional Palliative Care Program and the Division of Palliative Medicine,
      University of Alberta, Canada. It describes the content and format of the
      homepage and the process of publication. Over a six-month period there were 892
      visits to the site and 84 separate items of correspondence to the site's editors.
      Of these correspondence items, 36 were requesting further information regarding
      clinical and other programme information. Sixty-nine of the 84 communications
      came from North America and Europe. The pattern of readership is briefly
      discussed as are some of the potential advantages and challenges when utilizing
      this electronic medium. To promote the dissemination of reliable information on
      the Internet, the authors encourage other palliative care groups and
      organizations to publish on the WWW. The URL is http:/(/)www.palliative.org
      (previously http:/(/)www.caritas.ab.ca/approximately palliate).

PMID- 9519166
TI  - Relocation stress syndrome: the case of palliative care patients.
AB  - Transfer of patients from palliative care services to nursing homes is necessary
      at present when a patient is relatively stable, but does not have adequate
      support systems at home. With the ageing of the population and the increasing
      incidence of cancer, the need for inpatient palliative care beds is growing with
      corresponding pressure for patients to be transferred to nursing homes. Transfer
      to a nursing home in the general population has been described extensively in the
      gerontology literature where a critical early phase of relocation has been
      identified by a high incidence of morbidity and mortality. The vulnerability of
      terminally ill patients means that they are at increased risk of suffering from
      stress associated with a transfer. The prognosis of a patient may be shorter than
      the time required for adjustment to the patient's new home. The issues
      surrounding transfer of palliative care patients to nursing homes and possible
      strategies designed to reduce distress associated with transfers are explored.

PMID- 9519167
TI  - Palliative home care--the Calicut experience.
AB  - A three-year-old palliative care unit in Calicut, in the south Indian state of
      Kerala, started a home care service in June 1996. This paper reviews the first
      year of operation of the service; in this period 340 home visits were made. The
      service aims to deliver palliative care to the patients who are unable to reach
      the hospital, to empower patients to care for themselves and to empower the
      family to care for patients. One doctor and a few trained volunteers form the
      team. In addition to control of physical symptoms and emotional support, the home
      visits permitted minor procedures including nasogastric intubation,
      catheterization of bladder, dressing of wounds and intravenous fluid therapy. In
      some cases, the visits helped to change the attitude of families towards the
      patients--for example, allaying fear of contagion. In some instances, the visits
      changed the attitude of the neighbourhood towards the patient for the better. In
      spite of problems like the distances involved and bad roads, the experience of
      this team shows that a home care system is possible and essential for delivery of
      palliative care in India.

PMID- 9519168
TI  - The use of the genogram in palliative care.
AB  - A genogram is a format for drawing a family tree that records information about
      family members and their relationships over at least three generations. The
      genogram has been widely promoted as a useful tool for gathering, recording and
      displaying family information in order to practice family-oriented health care.
      We present a format for constructing the genogram and to outline the principles
      underlying its interpretation and application in clinical practice, so as to
      facilitate its use by physicians, nurses, psychologists, family therapists, and
      other professionals working with families in palliative care. Finally, the future
      potential of the genogram as a research and clinical tool in palliative care is
      discussed.

PMID- 9519169
TI  - How do palliative physicians manage venous thromboembolism?
AB  - This postal survey among 174 UK palliative physicians, aimed to assess current
      practice and perceived problems within the management of venous thromboembolism
      (VTE) in patients with advanced cancer. The questionnaire was returned by 131 out
      of 174 (74%) of the doctors surveyed. The most common estimated incidence of
      patients with VTE was 1-5%. The diagnosis of VTE is usually confirmed by further
      investigation and in general, outpatients are more likely to be anticoagulated
      than inpatients. Problems with anticoagulation include bleeding, international
      normalized ratio instability, appropriateness of anticoagulation, practical
      difficulties associated with monitoring, and recurrent VTE. Although probably
      less effective, 77 out of 128 (60%) of respondents use subtherapeutic regimes in
      order to minimize the risks. Patients with advanced malignancy and VTE are
      anticoagulated, if considered appropriate, by the vast majority of palliative
      physicians in the UK. Warfarin has been abandoned in favour of low-molecular
      weight heparin (LMWH) by 26%. LMWH provides anticoagulation with no need for
      monitoring, has no significant drug interactions and is not affected by liver
      dysfunction. Theoretically, LMWH is more effective than warfarin in the secondary
      prevention of VTE with less risk of bleeding.

PMID- 9519170
TI  - Tuberculosis in the hospice--a cause for concern?
AB  - Open pulmonary tuberculosis has been increasingly seen in HIV-infected patients
      in this hospice. Multidrug-resistant tuberculosis is a new and serious threat and
      two cases have occurred in our hospice in the past two years. This infection
      poses a health risk to staff, patients, relatives and volunteers. Palliative care
      teams in the hospice and community must have an index of suspicion for this
      infection, take active measures to ensure patient compliance with tuberculosis
      treatment and be prepared to implement infection control guidelines when needed.

PMID- 9519171
TI  - A randomized crossover study comparing the efficacy and tolerability of a novel
      once-daily morphine preparation (MXL capsules) with MST Continus tablets in
      cancer patients with severe pain.
AB  - The efficacy, tolerability and 24-h duration of action of MXL capsules, a novel
      once-daily morphine preparation, were compared with twice-daily morphine tablets
      (MST Continus tablets) in patients with severe cancer pain. Eighty-five patients
      were recruited to this randomized, double-blind, double-dummy, crossover study.
      There was no significant difference between the two treatment groups in the
      number of occasions that escape medication was required, the pain scores at each
      of three time points throughout the day, and the number of nights woken due to
      pain. Both preparations were well tolerated with no significant difference in the
      number or severity of reported symptoms and side-effects. Sixteen patients
      withdrew from the study, of whom 13 withdrew for nontreatment-related reasons.
      There was no difference between the preparations in terms of expressed treatment
      preference. MXL capsules were shown to provide effective analgesia over the 24-h
      dosing interval which was comparable to that of MST Continus tablets administered
      twice daily.

PMID- 9519172
TI  - Epidural complications and a case of malignant meningitis.
AB  - We report a case in which the signs of a malignant meningitis could have been
      confused with complications of an in-dwelling epidural catheter which was being
      used for analgesia. This confusion could have had disastrous implications for the
      patient's pain relief. We also discuss some of the issues and problems
      surrounding the use of in-dwelling epidurals in terminal care patients.

PMID- 9519173
TI  - Palliative medicine in India.

PMID- 9519174
TI  - Placebo-controlled trials in palliative care: the argument against.

PMID- 9519175
TI  - Use of sedatives in palliative medicine.

PMID- 9519176
TI  - The absence of 'cross-tolerance' when switching from oral morphine to transdermal
      fentanyl.

PMID- 9519177
TI  - Opioid responsive central pain of cerebrovascular origin: a case report.

PMID- 9519178
TI  - Management of young dyspeptic patients in the community.

PMID- 9519179
TI  - Localised carcinoma of the prostate: a paradigm of uncertainty.
AB  - The incidence and prevalence of prostate cancer is increasing. A number of
      aetiological factors including age, race, family history and diet have been
      implicated. The majority of patients present with disease which is amenable only
      to palliation. Digital rectal examination, serum prostate-specific antigen and
      transrectal ultrasound can lead to a prostatic biopsy. Transrectal ultrasound,
      magnetic resonance imaging, bone scan and a chest X-ray are used for staging. The
      management of localised cancer is shrouded in uncertainty. Three options exist,
      watchful waiting, radiotherapy, and radical total prostatectomy. The published
      data are inadequate for a valid comparison of these, and none has been shown to
      offer an advantage. Surgery, and to a lesser degree radiotherapy, have a
      significant morbidity. It is hoped that through better understanding our
      management of this disease will improve.

PMID- 9519180
TI  - Inhalation of chlorine gas.
AB  - The clinical features of acute chlorine gas inhalation, and its management are
      reviewed. Current medical views on the chronic effects of an acute overwhelming
      exposure on lung function (reactive airways dysfunction syndrome), and the more
      controversial field of lung disease secondary to repeated inhalations of lower
      concentrations of chlorine gas are discussed.

PMID- 9519181
TI  - Information technology in medical education: current and future applications.
AB  - Information technology has the potential to revolutionise the way medicine is
      learned by students and healthcare professionals. This potential was recognised
      by the General Medical Council in their 1993 report Tomorrow's doctors in which
      the need for future generations of doctors to be familiar with the application
      and scope of information technology is described. This paper focuses on the use
      of computers as aids to learning medicine and discusses two key applications of
      information technology to medical education: multimedia and the internet. The
      current use and potential for these areas of information technology are described
      and future developments discussed.

PMID- 9519183
TI  - Fabry's disease: a multidisciplinary disorder.
AB  - Fabry's disease is an X-linked hereditary disorder resulting in accumulation of a
      glycolipid (galactosylgalactosyl glucosylceramide) due to deficiency of alpha
      galactosidase A. The diagnosis can be made by histopathologic examination of skin
      biopsy, low activity of alpha-galactosidase in leucocytes and genetic
      examination. Treatment is symptomatic. We want to stress the multidisciplinary
      collaboration necessary to deal with this condition, in order to prevent
      acceleration of symptoms.

PMID- 9519182
TI  - Soft tissue tumours.
AB  - Any soft tissue swelling beneath the deep fascia should be considered a sarcoma
      until proven otherwise. As the most important factor in the primary treatment of
      these cancers is the adequacy of the primary surgical resection, it is vital to
      diagnose these malignant tumours pre-operatively. The modern treatment of soft
      tissue sarcomas may involve all modalities, but the most important aspect of
      treatment of a primary localised sarcoma is wide excisional surgery preserving
      limb function. Radiotherapy is a vital adjunct in high-grade tumours, or in
      tumours whose resectability is limited either by size or anatomical proximity to
      vital structures. Apart from a few chemosensitive sarcomas, the role of
      chemotherapy is limited to treatment of metastatic disease where documented
      response rates are no greater than 30%. As 50% of patients with high-grade
      sarcomas will die from metastatic disease, improvements in survival rates will
      only come from improvements in response to systemic therapy. No controlled trials
      have shown any survival benefit for adjuvant chemotherapy, although a recent meta
      analysis of published data has shown a trend to increased survival at two years.
      Multicentre randomised trials are ongoing. The prognosis of these lesions is
      highly variable, but is intimately related to the anatomical site (i.e.,
      resectability), and also the grade and size of the tumour.

PMID- 9519184
TI  - Cryptosporidiosis in persons with HIV infection.
AB  - Cryptosporidium parvum is an ubiquitous protozoan parasite that is a major cause
      of diarrhoea in individuals infected with human immunodeficiency virus. The
      hallmarks of infection include profuse watery diarrhoea which may become chronic
      in the severely immunosuppressed individual. No uniformly effective therapy
      exists. Current treatment relies upon a trial of anti-retroviral and specific
      anti-cryptosporidial medications, adequate fluid and nutritional support, and
      anti-motility agents.

PMID- 9519185
TI  - Improving management of duodenal ulcer disease.
AB  - Audit of treatment of duodenal ulcer disease has allowed management to improve
      and keep abreast of rapid advances in care. Eradication of Helicobacter pylori
      was assessed by 14C urea breath test one to two months after anti-Helicobacter
      therapy. The old triple therapy regime of bismuth, tetracycline and metronidazole
      for two weeks was found to be toxic and of low effectiveness (82%). Regimes with
      lansoprazole for one month and antibiotics for one week gave 90-98% success
      rates. The best success has been with regimes containing both clarithromycin and
      a nitro-imidazole. There was complete success in 98% of 109 patients given
      quadruple therapy with lansoprazole 30 mg daily for one month plus tetracycline
      500 mg twice daily, clarithromycin 250 mg twice daily and metronidazole 400 mg
      twice daily for one week.

PMID- 9519186
TI  - The use of over-the-counter medication by elderly medical in-patients.
AB  - Use of over-the-counter (OTC) medications by elderly patients is often not
      identified. This survey was performed to study the use of OTCs by medical in
      patients aged 65 and over. Data on the use of OTC medications before and during
      hospital admission were collected by questioning patients and case notes were
      examined for documentation of their use of OTC medications. OTC medications were
      used by 44 of 138 (32%) patients interviewed. Patients used a total of 70 OTC
      medications before admission and six OTC medications were being used during
      hospital admission. There was no documentation of pre-admission and in-hospital
      OTC medicine use in the clinical notes and patients had little knowledge of the
      potential harm some products can cause. As more products become available over
      the counter, doctors should record their use in patients' notes and patients
      should be encouraged to seek professional advice before purchasing OTC medicines
      and to read the product information leaflets.

PMID- 9519187
TI  - The views of medical students and junior doctors on pre-graduate clinical
      teaching.
AB  - A total of 277 third and fourth year medical students and 304 house officers and
      senior house officers were asked to prioritise the content and methods of
      clinical teaching. Response rates were poor, but similar to that in market
      surveys. Bedside teaching and medical clerking were considered the most valuable
      methods of teaching and training in practical procedures such as venepunctures
      and urinary catheterisation was seen as valuable. The design of new curricula in
      medical education will need to accommodate the views of its clients.

PMID- 9519188
TI  - Large airway obstruction by a chronic dissecting aortic aneurysm in the Marfan
      syndrome.
AB  - We describe a patient with the Marfan syndrome who presented with an acute aortic
      dissection. She underwent composite graft replacement of the aortic root. She
      returned two years later with dyspnoea and stridor due to tracheal compression by
      a large chronic dissection of the thoracic aorta. Marfan patients are at risk of
      chronic dissection involving the remaining distal aorta and require regular
      noninvasive assessment following surgery.

PMID- 9519189
TI  - Caecal adenocarcinoma with multiple synchronous small intestinal adenocarcinoma.
AB  - We describe a patient who presented with iron deficiency anaemia in whom both
      upper and lower gastrointestinal investigation were initially negative.
      Management included successive blood transfusions. Repeat investigation six
      months later revealed caecal adenocarcinoma. At laparotomy, the patient was also
      found to have two separate primary synchronous adenocarcinomas of the proximal
      small bowel. Right hemicolectomy and excision of the small bowel lesions were
      carried out. The patient eventually succumbed to the disease six weeks after
      discharge from hospital.

PMID- 9519190
TI  - Hypopituitarism due to lymphocytic hypophysitis in a patient with retroperitoneal
      fibrosis.
AB  - We present a 78-year-old woman with clinical acute hypopituitarism in whom
      pathologic findings showed lymphocytic hypophysitis and retroperitoneal fibrosis.
      Lymphocytic hypophysitis should be included in the differential diagnosis of
      hypopituitarism at any age. The association with idiopathic retroperitoneal
      fibrosis suggest an autoimmune origin for this entity.

PMID- 9519191
TI  - Cerebellar degeneration following neuroleptic malignant syndrome.
AB  - A 55-year-old woman with a history of bipolar affective disorder developed
      hyperpyrexia, rigidity and depressed consciousness (neuroleptic malignant
      syndrome) after commencing neuroleptic therapy. On regaining consciousness, she
      was mute and had signs suggesting pancerebellar involvement. Hyperpyrexia, which
      is a cardinal feature of neuroleptic malignant syndrome, may have caused
      cerebellar damage. Neuroleptic malignant syndrome needs both early recognition
      and prompt treatment to obviate devastating complications.

PMID- 9519192
TI  - Adrenocorticotropin-secreting carcinoid tumour identified and treated 12 years
      after presentation with Cushing's syndrome.
AB  - A case of Cushing's syndrome due to an adrenocorticotropin (ACTH) secreting
      bronchial carcinoid tumour is described. Endocrine assessment suggested ectopic
      ACTH syndrome, but imaging revealed no tumour. Bilateral adrenalectomy was
      performed, and computed tomographic scans of chest and abdomen were performed
      annually. A small nodule became apparent in the right lung 12 years after the
      presentation, which postoperatively was confirmed as the bronchial carcinoid
      tumour responsible for the ectopic ACTH syndrome.

PMID- 9519193
TI  - Perforated diverticulitis following extra-abdominal surgery.
AB  - The peritonitis of perforated diverticular disease is a life-threatening
      condition. We report three cases where it occurred following unrelated extra
      abdominal surgery and where surgical intervention proved to be the correct course
      of management. All cases were treated with a Hartmann's procedure; this is
      probably the safest option for purulent peritonitis in patients who are a high
      operative risk and have recently undergone major surgery.

PMID- 9519194
TI  - Late reversal reaction after 10 years of adequately treated leprosy.
AB  - Differentiation between a relapse or late reversal reaction following completion
      of regular drug therapy in patients with leprosy is often difficult, though it
      has definite therapeutic implications. The present case documents a late reversal
      reaction occurring an unusually long time after the completion of multi-drug
      therapy.

PMID- 9519195
TI  - Ketoacidosis and normal glucose tolerance.

PMID- 9519196
TI  - An unusual cause of 'pain in the neck'.

PMID- 9519197
TI  - Polydactyly and partial blindness.

PMID- 9519198
TI  - Parasite infection in an officer of an ocean liner.

PMID- 9519199
TI  - Abdominal pain in a cirrhotic patient with ascites.

PMID- 9519200
TI  - A vascular mass in the neck.

PMID- 9519201
TI  - Hyperthyroidism and dementia.

PMID- 9519202
TI  - Multiple ileal perforations.

PMID- 9519203
TI  - Shortness of breath and jaundice.

PMID- 9519204
TI  - Thrombophilia in a man with long-standing hypogonadism.

PMID- 9519206
TI  - The molecular mechanisms of drug action.

PMID- 9519205
TI  - Low-grade fever after prosthetic valve insertion and captopril therapy: an
      iatrogenic cause.

PMID- 9519207
TI  - Straightening out the renal tubule: advances in the molecular basis of the
      inherited tubulopathies.
AB  - Advances in the molecular genetics of inherited renal tubulopathies have allowed
      some insight into the normal mechanisms of tubular cation and anion reabsorption.
      It is now possible to view Bartter's syndrome, Gitelman's syndrome and
      pseudohypoaldosteronism type 1 as having genetic abnormalities which produce
      tubular defects that are similar to those induced by the pharmacological actions
      of loop diuretics, thiazide diuretics or potassium-sparing diuretics,
      respectively. Although these rare monogenic disorders with dramatic phenotypes
      seem to have little relevance to everyday clinical practice, it is possible that
      subtle abnormalities of the regulation of the ENaCs may play a role in low-renin
      forms of 'essential' hypertension. Similarly, subtle abnormalities in the
      function of the electroneutral sodium-(potassium)-chloride cotransporters (NKCC2
      and NCCT) and the renal CLC-type chloride channels (CLC5) may be major
      determinants of urinary calcium excretion with roles in the pathogenesis of
      'idiopathic' hypercalciuria and osteoporosis. Because of the intricate and
      diverse molecular mechanisms by which tubular reabsorption of water and solutes
      takes place in each different nephron segment, it is likely that other renal
      channels and transporters will be implicated in the pathogenesis of further
      monogenic disorders, and that these will allow additional insights into tubular
      functioning. Recent studies have demonstrated that in addition to abnormalities
      in the NKCC2 and ROMK1 genes, mutations at a third genetic locus can also cause
      Bartter's syndrome. Linkage studies, followed by mutational analyses have found
      deletions and point mutations in the gene encoding one of the TAL-specific
      chloride channels, CLCKB, in 17 Bartter's families. This chloride channel is
      similar in structure to CLC5, and is located on the long arm of chromosome 1.
      Importantly, there appears to be a phenotypic difference between subjects with
      Bartter's syndrome due to CLCKB abnormalities and those with NKCC2 or ROMK1
      mutations. Despite the fact that all of these Bartter's patients had significant
      hypercalciuria, nephrocalcinosis was not found in any of the 17 subjects with
      CLCKB mutations, compared to 19 of 20 patients with NKCC2 or ROMK1 mutations.
      These findings have also demonstrated a key role for CLCKB as a major basolateral
      chloride channel involved in mTAL sodium and chloride reabsorption (Figure 2).

PMID- 9519208
TI  - Mannose binding protein deficiency is not associated with malaria, hepatitis B
      carriage nor tuberculosis in Africans.
AB  - We retrospectively studied MBP genotypes in patients with malaria, tuberculosis
      (TB), and persistent hepatitis B virus (HBV) carriage, in clinics and hospitals
      in The Gambia. Children under 10 years with cerebral malaria and/or severe
      malarial anaemia, were compared with children with symptomatic, mild malaria, and
      controls of the same age and ethnicity. Adult TB cases with smear-positive
      pulmonary TB were compared with healthy blood donors from the same ethnic groups.
      Malaria cases and controls were tested for hepatitis B core antibody (anti-HBc)
      and surface antigen (HBsAg). TB patients were tested for HIV antibodies.
      Genotyping used sequence-specific oligonucleotide analysis to identify MBP
      variant alleles. Overall, 46% (944/2041) of patients and controls were homozygous
      for the wild-type MBP allele, 45% (922/2041) were carriers of a single variant
      allele and 8.6% (175/2041) had two variant alleles. Neither homozygotes nor
      heterozygotes for MBP variants were at increased risk of clinical malaria,
      persistent HBV carriage or TB. The most common mutation in Africans, the codon 57
      variant allele, was weakly associated with resistance to TB (221/794 in TB cases
      and 276/844 in controls, p = 0.037). MBP deficiency is not a significant risk
      factor for persistent HBV, severe malaria nor pulmonary TB in West Africa.

PMID- 9519209
TI  - Haemodynamic parameters predicting variceal haemorrhage and survival in alcoholic
      cirrhosis.
AB  - The relationship between the various haemodynamic abnormalities observed in
      cirrhosis and their prognostic value remains unclear. We report haemodynamic
      measurements on 96 patients with alcoholic cirrhosis (mean Childs-Pugh Score,
      CPS, 9.0 +/- 0.2, mean age 55.6 +/- 1.0 years) and assess their value in
      predicting variceal bleeding and death during a mean follow-up of 19.3 +/- 1.5
      months. Baseline CPS correlated with hepatic venous pressure gradient (HVPG) (p =
      0.001), azygos blood flow (p < 0.05), cardiac index (p < 0.05), and inversely
      with mean arterial pressure (p < 0.01) and systemic vascular resistance index (p
      < 0.05). Renal blood flow was not related to any haemodynamic parameter or CPS.
      Thirty-eight patients died during follow-up, and 16 had a variceal bleed. Death
      (p = 0.001) and variceal bleeding (p < 0.05) were more likely in patients with
      HVPG > 16 mmHg than in those with HVPG < 16 mmHg, and variceal bleeding was more
      likely in patients with HVPG > 12 mmHg (vs. HVPG < 12 mmHg, p < 0.05). HVPG also
      predicted death and variceal haemorrhage on univariate and multivariate analyses.
      No other haemodynamic parameter predicted death or bleeding. In alcoholic
      cirrhosis, severity of liver disease is related to HVPG, collateral blood flow
      and degree of systemic circulatory abnormalities. HVPG is a useful predictor of
      survival and variceal bleeding in these patients.

PMID- 9519210
TI  - The prognostic significance of acute renal failure after renal transplantation in
      patients treated with cyclosporin.
AB  - We studied 733 cadaveric renal transplant patients (747 transplants) under
      cyclosporin immunosuppression, to: (i) establish the risk profile for acute renal
      failure (ARF) after renal transplantation in a unit using many sub-optimal
      donors; (ii) assess the long-term prognostic relevance of ARF; and (iii) explore
      the synergistic prognostic significance of delayed graft function and acute
      rejection during the early post-transplant period. Transplanting from a non-heart
      beating or elderly donor, protracted cold ischaemia, haemodialysis immediately
      before transplant surgery, poor HLA matching, and grafting to a hypersensitized
      recipient without residual renal function, all independently predicted delayed
      graft function. This delay had no detrimental effect on patient or graft
      survival, but prolonged ARF was associated with increased mortality from
      infection. Late markers of graft dysfunction (poor graft function, proteinuria,
      hypertension) were highly prevalent among grafts affected by ARF, specially in
      prolonged ARF. Delayed graft function and early acute rejection showed a
      definite, albeit not strong, additive impact on late graft survival, and also on
      the prevalence of late markers of graft dysfunction.

PMID- 9519212
TI  - Treatment of Felty's syndrome with the haemopoietic growth factor granulocyte
      colony-stimulating factor (G-CSF).
AB  - Felty's syndrome (FS) (rheumatoid arthritis with neutropenia and splenomegaly)
      has a poor prognosis, largely because of the high risk of severe infection.
      Granulocyte colony-stimulating factor (G-CSF) is an emerging treatment for
      chronic neutropenia. We prospectively monitored its use in eight patients with
      recurrent infections or who required joint surgery. Significant side-effects were
      documented in five, including nausea, malaise, generalized joint pains, and in
      one patient, a vasculitic skin rash. In two patients treatment had to be stopped,
      and in these cases G-CSF had been started at full vial dosage (300 micrograms/ml
      filgrastim or 263 micrograms/ml lenograstim) alternate days or daily. G-CSF
      treatment was continued in three patients by restarting at reduced dose, and
      changing the proprietary formulation. G-CSF raised the neutrophil count, reduced
      severe infection, and allowed surgery to be performed. A combined clinical and
      laboratory index suggested that long-term treatment (up to 3.5 years) did not
      exacerbate the arthritis. Once on established treatment, it may be possible to
      use smaller weekly doses of G-CSF to maintain the same clinical benefit. One of
      the three patients whose FS was associated with a large granular T-cell
      lymphocytosis showed a reduction in this subset of lymphocytes during G-CSF
      treatment.

PMID- 9519211
TI  - Community-acquired Staphylococcus aureus bacteraemia in patients who do not abuse
      intravenous drugs.
AB  - Despite advances in antimicrobial therapy and intensive care support,
      Staphylococcus aureus continues to cause significant morbidity and mortality. We
      studied community-acquired S. aureus bacteraemia in a population where
      intravenous drug abuse is extremely uncommon, prospectively reviewing all such
      patients (n = 113) admitted to Groote Schuur Hospital from February 1986 to
      January 1991. Overall mortality was 35%. Factors associated with poor outcome
      were: confusion on presentation, failure to mount a febrile response, acute renal
      failure, adult respiratory distress syndrome, shock, endocarditis, disseminated
      intravascular coagulation and platelet count of < 100 x 10(9)/l. Only confusion,
      acute renal failure and shock were independently associated with death by
      stepwise regression analysis. Skin infections were the most commonly identified
      source of bacteraemia (22%), but in 58% of patients the source was not
      determined. Twenty-six percent of patients were diabetic. Almost all patients
      (90%) developed one or more complications. In those who survived, therapy was
      generally prolonged, with a median of 70 days and range of 7-393 days, depending
      on the associated complications. Community-acquired S. aureus bacteraemia is a
      serious condition associated with a high complication rate and mortality.

PMID- 9519213
TI  - Medical application of millimetre waves.

PMID- 9519214
TI  - Anti-coagulation in atrial fibrillation.

PMID- 9519215
TI  - Pathogenesis of tropical pulmonary eosinophilia: parasitic alveolitis and
      parallels with asthma.

PMID- 9519216
TI  - Diaphragm shortening and intrathoracic pressure during hypercapnia in rats.
AB  - The purpose of this study was to determine the relationship between intrathoracic
      pressure (delta ITP) and diaphragm shortening (DS) during the development of
      diaphragm fatigue. Fatigue of the diaphragm was produced by having rats breath
      15% CO2 in O2. Diaphragm shortening increased significantly to 178% of control
      during the first 5 min of hypercapnia and then decreased to 86% of control at
      approximately 80 min. Twenty minutes after terminating hypercapnia, DS increased
      to 115% of the prehypercapnic value. delta ITP increased to 199% of control
      following 5 min of hypercapnia and continued to increase, reaching 267% of
      control at the end of the hypercapnic period. Twenty minutes later, delta ITP was
      147% of control. These results illustrate that during increased respiratory work,
      DS can decrease while intrathoracic pressure remains increased. These findings
      suggest that intrathoracic pressure may not always reflect the contractile status
      of the diaphragm. These findings are consistent with other studies indicating
      that as the diaphragm fatigues, accessory respiratory muscle activity increases
      to maintain delta ITP.

PMID- 9519217
TI  - Hypo-osmolar aerosol induces hyperventilation in chronic non-asthmatic rhinitics.
AB  - The effect of a hypo-osmolar aerosol on transcutaneous O2 and CO2 time course
      (PtcO2, PtcCO2) was investigated in subjects affected by chronic non-atopic
      rhinitis, without any history of asthmatic symptoms and no airways hyper
      responsiveness. Twelve normal subjects and 12 subjects affected by chronic
      idiopathic rhinitis, who had normal responsiveness to both hypo-osmolar aerosol
      and methacholine challenge as measured by the decrease in FEV1 (mean FEV1
      decrease = 5% and PC20 > 16 mg, respectively) were studied. By means of a
      transcutaneous mono-electrode, it was possible to study the time course of PtcO2
      and PtcCO2 during and after a 5-min inhalation of ultrasonically nebulized
      distilled water (output 2 ml/min-1). A significant decrease in PtcCO2 and
      increase in PtcO2 were observed during the challenge in rhinitics as compared
      with normal subjects [maximum decrease and maximum increase expressed as mean
      value (+/- SD) were -22% (+/- 6.9) and +12.6% (+/- 7.2), respectively]. No
      significant changes in either PtcCO2 and PtcO2 were observed after the test. The
      results of this study suggest that patients affected by idiopathic chronic
      rhinitis with absence of bronchial hyper-responsiveness may present a
      hyperventilatory response to the inhalation of hypo-osmolar aerosol; the
      mechanism of such a response might be due to an upregulation of the irritant
      receptors of the upper airways.

PMID- 9519218
TI  - Compartmentalization of pro-inflammatory cytokines in tuberculous pleurisy.
AB  - Increased levels of interleukin-6 (IL-6) and IL-8 are found in various
      immunologically mediated inflammatory disorders. Concentrations of IL-6, IL-8 and
      the soluble form of the IL-6 receptor (sIL-6R) were determined in serum and
      effusion fluid of 25 patients with tuberculous pleurisy utilizing enzyme linked
      immunosorbent assays (EIA). Serum IL-6 levels were only slightly increased in
      patients with tuberculous pleurisy in comparison to controls (11.1 +/- 2.1 vs 7.3
      +/- 1.0 pg ml-1). IL-8 could not be detected in the serum of tuberculosis
      patients, but it was detected in the serum of healthy controls (8.0 +/- 1.5 pg ml
      1). In comparison to serum, IL-6 and IL-8 were found in high concentrations in
      pleural effusions (IL-6: 932 +/- 70 vs 11.1 +/- 2.1 pg ml-1, P < 0.0001; IL-8:
      450 +/- 85 vs 0 +/- 0 pg ml-1). In contrast, sIL-6R concentrations were much
      higher in serum compared to pleural effusion levels [30,477 +/- 1905 vs 9881 +/-
      1177 pg ml-1, P < 0.0001 (mean +/- SEM)]. The authors conclude that elevated
      levels of IL-6 and IL-8 in pleural effusions are compartmentalized at the site of
      active disease. The low levels of sIL-6R in the presence of high levels of IL-6
      in pleural effusions, and the high levels of sIL-6R in the presence of low levels
      of IL-6 in serum suggest that the expression or shedding of sIL-6R may be
      downregulated in the presence of excessive amounts of IL-6.

PMID- 9519219
TI  - Re-breathing vs single-breath TLCO in patients with unequal ventilation and
      diffusion.
AB  - The single-breath (SB) method for determining the transfer factor for carbon
      monoxide (TLCO) is of limited value for the detection of diffusion disorders on
      the alveolar level, because the results are influenced by unequal distribution of
      ventilation and diffusion. The rebreathing method (RB) is thought not to be
      influenced by these inequalities. To the authors' knowledge, no study has
      measured both TLCORB and TLCOSB systematically and compared them with regard to
      the influence of unequal ventilation and diffusion. Therefore, the present study
      measured total lung capacity (TLC) as well as TLCO, both with the RB vital
      capacity method and the SB method, using the same apparatus in 10 healthy
      subjects and in 35 patients with chronic obstructive pulmonary disease (COPD).
      These patients are known to have increased unequal ventilation and diffusion in
      comparison with healthy subjects. In the healthy subjects, a small difference was
      found between TLC measured with the RB method (TLCRB) divided by the predicted
      value (TLCRB/pred) and TLCSB/pred (mean difference 0.07; SE = 0.02); no
      significant difference was found between TLCORB divided by the predicted value of
      TLCOSB (TLCORB/pred) and TLCOSB/pred. In the COPD patients, however, TLCRB/pred
      was larger than TLCSB/pred (mean difference 0.17; SE = 0.02) and TLCORB/pred was
      larger than TLCOSB/pred (mean difference 0.23; SE = 0.05). Multiple regression
      analysis revealed that in the COPD patients, 54% of the variance of the
      difference between TLCRB/pred and TLCSB/pred, and 76% of the variance of the
      difference between TLCORB/pred and TLCOSB/pred, were explained by parameters
      related to unequal ventilation and diffusion. In 25 of the 35 COPD patients,
      TLCOSB/pred was less than 0.8, whereas in 11 of these 25 patients, TLCORB/pred
      was more than 0.8. This difference was significant (P = 0.0005). In these 11
      patients, the SB measurement resulted in the incorrect diagnosis of a diffusion
      disorder on the alveolar level. The RB method, however, never resulted in the
      diagnosis of a diffusion disorder when TLCOSB/pred was larger than 0.8. It is
      concluded that in a significant number of COPD patients, TLCOSB is below the
      normal range, whereas TLCORB is not below the normal range. This difference
      between TLCORB and TLCOSB is related to the combined effect of unequal
      ventilation and diffusion, and is of clinical importance for the detection of a
      diffusion disorder on the alveolar level.

PMID- 9519220
TI  - Electrocardiographic changes in obstructive sleep apnoea syndrome.
AB  - Obstructive sleep apnoea syndrome (OSAS) has acute and chronic effects on the
      cardiovascular system. Both right and left sides of the heart are affected.
      Electrocardiographic pattern was studied in 190 OSAS patients. One or more of the
      following were found: persistent deep S in lateral chest leads V5, V6 (79%), left
      anterior hemiblock (71%), RS pattern with deep S wave in leads aVf, I, II and III
      (71, 55, 26 and 22% respectively), right axis (6%), right bundle branch block
      RBBB (5%), QRS voltage criteria of left ventricular hypertrophy (4%), QR pattern
      in V1 (4%) and none of the above (11%). The most common patterns were deep S wave
      in leads I, aVf, V6 with left axis (27%), deep S wave in leads II, III, aVf and
      V6 with left axis (12%), and deep S wave in leads I, II, III, aVf and V6 with
      left axis (11%). There was statistically significant difference in
      polysomnographic data and daytime PaO2 between OSAS patients with and without ECG
      findings. The latter had the mildest evidence of disease (P < 0.01). The findings
      suggest prevalence of late depolarization of hypertrophied right outflow tract
      and/or left anterior fascicular block. With progression of OSAS, there is
      evolution of an ECG pattern that is peculiar for the disease, and helpful in
      diagnosing OSAS patients when other disease entities are excluded.

PMID- 9519221
TI  - nCPAP treatment interruption in OSA patients.
AB  - This study has investigated the effect of interrupting nasal continuous positive
      airway pressure (nCPAP) therapy on 10 obstructive sleep apnoea (OSA) patients
      (nine male, one female) (53.6 +/- 7.3 years) treated over 2 years. The effect of
      nCPAP interruption was determined by variations in sleep counts and gasometric
      values during five consecutive nights. On the first night, the patient used his
      habitual nCPAP. On the remaining nights, nasal nCPAP was not applied. The apnoea
      hypopnoea index (AHI) was found to increase significantly in the second night,
      attaining a similar level to that of the basal study (2 years ago). SaO2 minimum
      decreased and PaCO2 increased in the second night with respect to the first
      night. The interruption of nCPAP therapy in OSA patients treated over a long
      period of time increases the sleep counts and impairs the gasometric parameters.
      Consequently, any change in nCPAP time therapy must be checked to avoid negative
      effects.

PMID- 9519222
TI  - A rapid dosimetric methacholine challenge in asthma diagnostics: a clinical study
      of 230 patients with dyspnoea, wheezing or a cough of unknown cause.
AB  - The rapid methacholine challenge test using a pocket turbine spirometer (Micro
      Spirometer) and the Spira Elektro 2 dosimeter was performed with 230 consecutive
      patients who had dyspnoea, wheezing or a prolonged cough of unknown cause.
      Patients with previous asthma diagnoses as well as those who had used inhaled
      steroids during the preceding 4 weeks were excluded. Seventy-eight patients (34%)
      were methacholine positive (PD20FEV1 < or = 6900 micrograms) 47 (60%) of whom had
      a final diagnosis of American Thoracic Society (ATS) criteria fulfilling
      bronchial asthma. One hundred and fifty-two patients (66%) were methacholine
      negative (PD20FEV1 > 6900 micrograms) 14 (9%) of whom had bronchial asthma
      according to clinical evaluation. Increased bronchial responsiveness was strongly
      associated with ATS criteria fulfilling asthma (P < 0.0001). When PD20FEV1 was
      used, 47 (77%) of the asthmatic patients were hyper-responsive (range 40-6900
      micrograms) compared to 31 (18%) of the non-asthmatic patients (range 160-6900
      micrograms). When using PD15FEV1, 51 (84%) of the asthmatic patients (range 28
      6900 micrograms) and 52 (31%) of the non-asthmatic patients (range 100-6900
      micrograms) were hyper-responsive. The level of bronchial responsiveness measured
      by both PD20FEV1 and PD15FEV1 differed significantly between asthmatic and non
      asthmatic patients (P < 0.0001). Hyper-responsiveness was associated with an
      increased daily variation in peak expiratory flow (PEF) (P < 0.0001) and an
      increased number of blood eosinophils (P < 0.0001). Hyper-responsiveness was also
      associated with decreased levels of FEV1 and percentages of predicted FEV1 (P =
      0.04 and P < 0.0001, respectively). Stepwise logistic regression analysis showed
      that the number of positive prick results (OR = 1.15, 95% CI 1.01-1.31), blood
      eosinophils (1.004, 1.00-1.01), level of FEV1 (0.56, 0.36-0.87) and current
      smoking (2.36, 1.00-5.59) were factors significantly associated with the
      probability of hyper-responsiveness. Age, gender, atopy, pets and a history of ex
      smoking were not significantly associated with hyper-responsiveness, neither in
      univariate nor in multivariate analyses. The Bayesian analysis was used to
      investigate the diagnostic value of the rapid methacholine challenge test. A
      receiver operator characteristic curve demonstrated that PD20FEV1 separated
      asthmatic and non-asthmatic patients better than PD15FEV1. The best cutoff value
      of PD20FEV1 was 6000 micrograms, but the difference from 6900 micrograms was
      minimal. The best results of the test using a PD20FEV1 cutoff point of 6900
      micrograms (PPV: 0.80, NPV: 0.79) were obtained when the pre-test probability was
      0.48. The interval security of the test was established by a pre-test probability
      between 0.19 and 0.78. Maximal positive (0.34) and negative (0.31) final gains
      were achieved when pre-test probabilities were 0.33 and 0.65, respectively. The
      cutoff level of 150 micrograms gave 100% of specificity and predictive value of a
      positive test for clinical asthma diagnosis. The Bayesian analysis approach
      demonstrated that the test is useful in asthma diagnostics if not performed on
      patients with lowest or highest probabilities of asthma.

PMID- 9519223
TI  - Serum concentrations of lignocaine and its metabolite monoethylglycinexylidide
      during fibre-optic bronchoscopy in local anaesthesia.
AB  - Fibre-optic bronchoscopy was performed in local anaesthesia using lignocaine.
      Serum concentrations of lignocaine and its active metabolite
      monoethylglycinexylidide (MEGX) were measured in 16 patients at regular intervals
      up to 120 min after administration. Lignocaine was administered as an aerosol in
      the upper respiratory tract and as a solution in the bronchial tree. The total
      dose of lignocaine ranged from 243 to 608 mg (2.4-8.0 mg kg-1 body weight). The
      dose of lignocaine given as an aerosol ranged from 163 to 508 mg (1.6-6.6 mg kg
      1) and the dose given as a solution ranged from 60 to 180 mg (0.8-2.5 mg kg-1).
      The highest median serum lignocaine concentration, 10.5 mumol l-1, was measured
      20 min after administration. None of the patients had toxic serum lignocaine
      levels (> 26 mumol l-1) or adverse effects. The highest median serum MEGX
      concentration, 1.7 mumol l-1, was measured 120 min after administration. The dose
      of lignocaine, expressed in mg per kg body weight correlated with serum
      lignocaine and serum MEGX (rs = 0.47 and rs = 0.39, respectively). Lignocaine is
      a clinically safe, local anaesthetic agent provided the total dose does not
      exceed 6-7 mg kg-1 body weight.

PMID- 9519224
TI  - Comparative study of budesonide as a nebulized suspension vs pressurized metered
      dose inhaler in adult asthmatics.
AB  - The study objective was to compare the effect of budesonide administered as a
      nebulized suspension as compared to a spray with a spacer in adult asthmatics. In
      a double-blind, double-dummy crossover study, 26 adult patients with moderately
      severe unstable asthma were randomized to three 4-week treatment periods with
      budesonide 0.8 mg b.i.d. administered by a pressurized metered-dose inhaler
      (pMDI) with spacer (Nebuhaler) and budesonide 1 mg and 4 mg b.i.d. administered
      by a Pari Inhalier Boy jet nebulizer. The nebulizer was activated only during
      inspiration. The total mass output was similar from the two devices but their
      fraction of small particles differed by a factor of 2 in favour of pMDI. Effect
      was evaluated from daily home measurements of peak expiratory flow (PEF), need of
      beta 2-agonist and symptom scores. Plasma cortisol and budesonide levels were
      measured in a subgroup of 10 patients. A consistent trend showed the nebulizer
      treatment to be at least as efficient as the pMDI plus spacer treatment. In
      actual fact, the apparent order of effect was: 4 mg nebulized suspension
      treatment > or = 1 mg nebulized suspension treatment > or = 0.8 mg pMDI with
      spacer treatment. Plasma budesonide and plasma cortisol also exhibited dose
      related levels independent of device. The adverse effects reported appeared to be
      related to the dose rather than delivery device. Accordingly, the effect was
      related to total mass output, rather than to the small particle fraction of the
      budesonide aerosol. These results attest to the efficiency of jet-nebulized
      budesonide suspension, and indicate nebulized budesonide to be equipotent to
      standard budesonide therapy delivered by pMDI with Nebuhaler, provided
      nebulization is synchronized with inspiration and no loss of aerosol occurs
      during expiration.

PMID- 9519225
TI  - Oral corticosteroid treatment during long-term oxygen therapy in chronic
      obstructive pulmonary disease: a risk factor for hospitalization and mortality in
      women.
AB  - Pharmacological therapy can influence morbidity and mortality in severe chronic
      obstructive pulmonary disease (COPD). Long-term domiciliary oxygen therapy (LTOT)
      improves survival in COPD with chronic hypoxaemia. Oral steroid medication has
      been associated with improved survival in men and increased mortality in women,
      while inhaled steroid medication has been associated with a reduction in the
      exacerbation rate. We have analysed the relationships between pharmacological
      therapy including oxygen therapy, sex, performance status and need for
      hospitalization and mortality in 403 patients with COPD (201 men) after their
      registration in a national oxygen register for LTOT. The mean value of days spent
      in hospital per year was 44. An increased need of hospital care was independently
      predicted by a poor performance status, high age and, in women, orally
      administered steroid medication. Hospital admissions were significantly longer in
      the terminal stage of COPD among women receiving oral steroid medication.
      Increased mortality was predicted by a poor performance status and, in women,
      oral steroid treatment. Predictors of morbidity and mortality during LTOT were
      found to coincide. The increased mortality in women receiving oral steroid
      medication was found to be associated with an increased need of hospital care due
      to longer hospital stays during the terminal stage of the disease. When analysing
      effects and side-effects of steroid medication in COPD, the possibility of sex
      related differences should be considered.

PMID- 9519227
TI  - Blood eosinophil and monocyte counts are related to smoking and lung function.
AB  - The aim of this study was to investigate the predictive value of peripheral
      eosinophil and monocyte blood counts regarding lung function in smokers and non
      smokers, and to investigate the influence of smoking on these cell counts. Forced
      expiratory volume in 1 s (FEV1) measurements and blood samples were collected
      from 298 non-atopic smokers and 136 never-smokers. Blood samples were repeated in
      160 smokers after cessation of smoking (quitters) and 30 continuing smokers, 2,
      6, 12 and 26 weeks after smoking cessation. Monocyte (P < 0.05) but not
      eosinophil blood counts were higher in never-smokers compared to smokers. In
      never-smokers, blood eosinophil counts and monocyte counts correlated inversely
      (P < 0.05) and directly (P < 0.01), respectively, with standardized FEV1
      residuals (FEVR). In smokers, blood eosinophil (P < 0.05) and monocyte (P < 0.05)
      counts correlated directly with FEVR independent of smoking history. After
      smoking cessation, monocyte blood counts (P < 0.05) increased. Both eosinophil
      and monocyte blood counts showed a greater increase in quitters with decreased
      lung function (P < 0.05). Former heavy smokers had higher blood eosinophil (P <
      0.05) but lower monocyte (P < 0.05) count increase than had former light smokers.
      These data suggest that smoking influences eosinophil and monocyte blood counts
      and that this is associated with a small negative effect on lung function.
      Eosinophil blood counts had an opposite relation to lung function in smokers and
      non-smokers. Further research should include investigations of relations between
      smoking and stimulatory factors for recruitment and activity of eosinophils and
      monocytes.

PMID- 9519226
TI  - Clinical factors that affect blood gases in non-smoking women with chronic liver
      disease.
AB  - Chronic liver disease is often accompanied by hypoxaemia. We investigated the
      clinical factors that were related to the arterial oxygen tension (PaO2) in 40
      women, all non-smokers with chronic liver disease. They were positive for
      hepatitis C virus (HCV) antibody and had no evidence of cardiopulmonary disease.
      Arterial blood was collected from patients at rest (> 15 min) for analysis of
      blood gases. We determined the correlation between blood gas tension and the
      clinical variables, i.e. the presence or absence of skin manifestations such as
      cutaneous spider nevi and palmar erythema, the presence or absence of
      splenomegaly, vital capacity, forced expiratory volume in one second, V25/body
      height, serum alanine aminotransferase (AST), serum asparate aminotransferase
      (ALT), serum cholinesterase, serum gamma-globulin/total protein, excretion of
      indocyanine green at 15 min (15-min retention rate, ICG level), blood level of
      ammonia, blood level of endotoxin, plasma level of glucagon and the serum level
      of type IV collagen-7S. The mean level of PaO2 was 78 +/- 11 (range: 43-95) torr.
      The mean alveolar-arterial oxygen tension gradient (A-aDO2) was 19 +/- 13 (range:
      2-60) torr. Multiple regression analysis used PaO2 and A-aDO2 as objective
      variables, and the clinical findings as explanatory variables. The explanatory
      variables that were significantly correlated with blood gas values were ICG
      level, blood level of endotoxin and presence of skin manifestations. The ICG
      level showed a high correlation with blood gas values; the ICG level increased,
      the PaO2 decreased (r = -0.69), while the A-aDO2 showed a high positive
      correlation (r = +0.78, P < 0.001). Findings suggest that a reduction in hepatic
      blood flow and hepatocellular function interfere with the inactivation of
      vasoactive substances such as endotoxin by the liver, leading to the development
      of skin manifestations, the dilatation of intrapulmonary capillaries and the
      induction of hypoxaemia.

PMID- 9519228
TI  - Characteristics and complaints of patients prescribed long-term oxygen therapy in
      The Netherlands.
AB  - In patients prescribed long-term oxygen therapy (LTOT), compliance is often poor.
      Both patient- and treatment-related factors seem to be involved. As a base for
      improvements in LTOT, the characteristics and complaints of LTOT patients were
      investigated. A survey was set up in a random sample of clients of the largest
      oxygen company in the Netherlands. Patients were selected if they were > or = 18
      years old, had a phone and if they had had oxygen equipment for > or = 6 months.
      All patients were visited at home by a medical student. Data are presented for a
      total of 528 patients (response rate 62%). The typical LTOT patient was a 70-year
      old male with chronic obstructive pulmonary disease (COPD), who had had oxygen
      equipment for 3.5 years and who used oxygen cylinders and nasal cannulae for 13 h
      day-1. Twenty percent of the patients still smoked. Although LTOT was prescribed
      in 80% of the patients by a chest physician, prescription was often inadequate.
      Only 33% of the patients were informed adequately about the therapy. Twenty
      percent of the patients used oxygen for fewer hours per day than prescribed. Non
      compliant patients were mainly men (P = 0.006) and more often ashamed of their
      therapy (P = 0.023) than compliant patients. The blood oxygen level was monitored
      regularly in 73% of the patients. Most complaints concerned the oxygen equipment,
      especially the concentrator. The single most important complaint had to do with
      restricted autonomy. Only 19% of the patients had no complaints at all. It is
      concluded that LTOT should be improved with regard to the education, motivation
      and monitoring of patients. The prescribing physician needs to be included in an
      education programme. Given the numerous problems these patients experience, LTOT
      should be improved in particular with regard to equipment convenience.

PMID- 9519230
TI  - Do patients using long-term liquid oxygen differ from those on traditional
      treatment with oxygen concentrators and/or compressed gas cylinders? A comparison
      of two national registers.
AB  - Long-term oxygen therapy (LTOT) in patients with chronic hypoxaemia is an
      expanding field. Traditional stationary oxygen, with and without portable
      compressed gas cylinders, and portable liquid oxygen equipment is available
      today. No official guidelines exist for the prescription of liquid oxygen vs
      traditional oxygen supply in LTOT, although it is generally though that patients
      receiving liquid oxygen are younger and less seriously affected. The authors
      tested this hypothesis by comparing register data from two national Scandinavian
      registers of patients on LTOT in the same time period; one including all the
      patients on traditional oxygen treatment alone, e.g. concentrators and compressed
      gas cylinders (n = 1039), the other including all the patients using portable
      liquid oxygen alone (n = 117). About 80% of the patients in both groups suffered
      from chrome obstructive pulmonary disease. Younger patients were found in the
      liquid oxygen group (P < 0.004), but with clinically slightly worse blood gas
      derangement (mostly statistically significant). They had higher frequency of
      previous or present oedema (P < 0.0001), and there were more smokers in this
      group (P < 0.0001). No significant differences were seen with respect to sex
      distribution or oxygen delivery systems. Higher oxygen dose and longer daily
      oxygen treatment (P < 0.0001) were prescribed for the liquid oxygen patients
      compared with the patients on traditional oxygen with statistically higher oxygen
      tension during the prescribed treatment. A slight further increase in PaCO2 was
      seen in both groups during oxygen treatment, of doubtful significance. Compared
      with patients on traditional oxygen, liquid oxygen thus appears to be prescribed
      for younger patients, independent of clinical status or blood gas levels.

PMID- 9519229
TI  - The enhanced inflammatory response in non-small cell lung carcinoma is not
      reflected in the alveolar compartment.
AB  - An inflammatory response has been observed in lung cancer both locally and
      systemically. The aim of the present study was to investigate whether the
      alveolar compartment was involved in the inflammatory response in non-small cell
      lung carcinoma (NSCLC). Both inflammatory mediators in bronchoalveolar lavage
      fluid (BALF) and cytokines produced by alveolar macrophages (AM) were
      investigated. Twenty patients with newly detected NSCLC and nine control subjects
      were studied. The patients had not been treated with chemotherapy, radiotherapy
      or with systemic or inhaled corticosteroids. All patients and control subjects
      were current smokers or stopped smoking recently. BAL was performed in the
      affected lung as well as in the contralateral lung of NSCLC patients, and only
      unilaterally in control subjects. Comparable results were demonstrated for the
      levels of the of the inflammatory mediators TNF-a, Interleukin (IL)-6, IL-8, both
      soluble TNF receptors and the soluble adhesion molecules E-selectin and
      intercellular adhesion molecule (ICAM)-1 between the affected lung and the
      contralateral lung in the NSCLC population as well as between the NSCLC
      population and the control subjects. Moreover, no significant differences in
      cytokine profiles of AM were found between AM obtained from the affected lung and
      from the contralateral lung. Although BAL is a useful tool in the diagnostic
      procedure for NSCLC, the present findings suggest that BAL does not reflect the
      enhanced inflammatory state, as reported in plasma and in the interstitial
      compartment around the tumour cells in NSCLC.

PMID- 9519231
TI  - Differences in sensitivity, maximal response and position of the concentration
      response curve to methacholine between asthmatics, patients with allergic
      rhinitis and healthy subjects.
AB  - The aim of this study was to detect differences in maximal response and position
      of the concentration-response curves to methacholine between asthmatics and
      subjects with allergic rhinitis. A total of 228 adults (107 mild asthmatics, 96
      allergic rhinitics and 25 healthy control subjects) were challenged with
      methacholine. The test was interrupted when FEV1 dropped by more than 40% or when
      the highest concentration of methacholine (200 mg ml-1) had been administered.
      Concentration-response curves were characterized by their PC20 (concentration of
      methacholine that produced 20% fall in FEV1 = airway sensitivity), and if
      possible, by their EC50 (concentration of methacholine that produced 50% of the
      maximal response = position) and level of plateau. The proportion of subjects
      with plateau was significantly lower in asthmatics (18.7%) than in either
      allergic rhinitics (57.3%) or healthy subjects (92%). It was also significantly
      lower in allergic rhinitics than in healthy subjects. The level of plateau for
      asthmatics was (means +/- SD) 31.5 +/- 5.5%, compared with 20.8 +/- 8.1% in
      allergic rhinitics and 13.7 +/- 6.7% in healthy subjects (P < 0.01). It was also
      higher in allergic rhinitics than in healthy subjects (P < 0.01). The EC50 values
      were decreased in asthmatics when they were compared with either allergic
      rhinitics or healthy subjects (geometric mean EC50: asthmatics = 2.7 mg ml-1,
      allergic rhinitics = 6.2 mg ml-1, healthy subjects = 8.7 mg ml-1; P < 0.01), but
      no significant differences were detected between allergic rhinitics and healthy
      subjects. These results demonstrate that in subjects with allergic rhinitis, the
      prevalence and level of the plateau on the methacholine concentration-response
      curve is intermediate between that of asthmatics and normals. Furthermore, while
      the asthmatic curves differ from normal in having both an increased maximal
      response and a leftward shift, the rhinitic curves differ only in terms of
      plateau level. These results suggest that airway responsiveness in asthma and
      allergic rhinitis may be a consequence of mechanisms that are at least partially
      different.

PMID- 9519232
TI  - Clinical experience with fluticasone propionate in asthma: a meta-analysis of
      efficacy and systemic activity compared with budesonide and beclomethasone
      dipropionate at half the microgram dose or less.
AB  - The relative clinical efficacy and systemic effects of different inhaled
      corticosteroids is controversial. To obtain further information on this matter,
      the authors have performed meta-analysis of seven trials comparing fluticasone
      propionate (FP) with budesonide (Bud), and seven trials comparing FP with
      beclomethasone dipropionate (BDP) for the treatment of asthma of all severities
      in adult and paediatric patients. In all cases, the drugs were compared at
      clinically equivalent doses, i.e. FP was given at half (or less) the microgram
      dose. The total number of patients was 1980 (1000 treated with FP 200-800
      micrograms day-1 and 980 with Bud 400-1600 micrograms day-1), and 1584 patients
      in the second analysis (780 treated with FP 200-1000 micrograms day-1 and 804
      with BDP 400-2000 micrograms day-1). FP significantly improved mean morning peak
      expiratory flow rate (PEFR) compared with Bud, with an overall difference of +11
      l min-1. Analysis of serum cortisols showed no differences between FP and Bud
      treatment at low doses, but at higher dosages, and overall, significant
      differences in favour of FP were observed. In the second meta-analysis, no
      significant differences in PEFR were observed between FP and BDP in any of the
      seven individual studies or in the pooled analysis. Analysis of serum cortisols
      showed a similar trend to the previous analysis, however, no overall difference
      in serum cortisol results were seen between FP and BDP. In conclusion, the pooled
      analysis shows that FP at half the dose (or less) is more effective than Bud and
      as effective as BDP in improving PEFR; in addition, these improvements were
      achieved with a reduction in cortisol suppression compared with BUD and with no
      greater degree of cortisol suppression compared with BDP. This demonstrates, in
      patients with asthma, that FP has an improved efficacy to safety ratio compared
      with older inhaled corticosteroids.

PMID- 9519233
TI  - A comparison of the performance of two modern multidose dry powder asthma
      inhalers.
AB  - Little is known about the shot potency and dose consistency of many of the
      inhalers in common use, and until recently there has been little consensus over
      the best way to evaluate these parameters. Since marked effects can be achieved
      with the inhaled route, more information is needed about the dosing
      characteristics of all available inhalers. As there are now two multidose powder
      inhalers available in the U.K. capable of supplying 1 month or more of treatment,
      this study was designed to compare the delivery characteristics of these two dry
      powder inhalers delivering glucocorticosteroids. The method used was in vitro
      analysis of the emitted dose and fine particle fraction throughout the life of
      five of each type of device. The multidose powder inhaler delivered between 87
      and 93% of the label claim dosage, whilst the reservoir device delivered 40-58%.
      There was no fall off of shot potency towards the end of either device's life.
      Fine particle fraction for the multidose and reservoir systems, was 21 and 18%,
      respectively, at 60 l min-1 flow, but fell to 16 and 6% at 28.3 l min-1. In
      conclusion, there were statistically significant differences (P < 0.0001) in the
      drug emission of both dose and fine particle fraction of these two powder
      inhalers.

PMID- 9519235
TI  - A case of allergic bronchopulmonary aspergillosis successfully treated with
      itraconazole.

PMID- 9519234
TI  - Is high-dose fluticasone propionate via a metered-dose inhaler and Volumatic as
      efficacious as nebulized budesonide in adult asthmatics?
AB  - The efficacy and tolerability of fluticasone propionate (FP) 2 mg daily via a
      metered-dose inhaler and Volumatic (Glaxo Wellcome) spacer device was compared
      with nebulized budesonide (nBUD), 2 and 4 mg daily, in a multi-centre, open
      label, cross-over study of adult asthmatics. Patients received, in random order,
      either 4 weeks of treatment with FP followed by 4 weeks of treatment with nBUD,
      or vice versa, with an intervening 4 week 'wash-out' period between treatments.
      Thirty patients completed the study, of whom 24 were evaluable. In terms of the
      primary efficacy parameter, change in mean morning peak expiratory flow (PEF) (l
      min-1) from baseline to the fourth week of each treatment period, FP was more
      effective than nBUD [mean difference (FP-nBUD) 21.1 l min-1, P = 0.007, 95% CI
      (6.5, 35.7)]. Sub-group analysis demonstrated FP to be superior to the 4 mg nBUD
      [mean treatment difference (FP-nBUD) 42.9 l min-1, P = 0.026, 95% CI (7.1, 78.8)]
      and at least as efficacious as the 2 mg nBUD sub-group [mean treatment difference
      (FP-nBUD) 10.2 l min-1, P = 0.211, 95% CI (-6.5, 26.9)]. Furthermore, larger
      reductions in diurnal variation were observed during FP treatment [mean treatment
      difference (FP-nBUD) -4.4 percentage points, P = 0.028, 95% CI (-8.4, -0.5)].
      There was no significant difference between the treatments for the proportion of
      symptom-free 24 h periods. Of those expressing a preference, significantly more
      patients found FP via a metered-dose inhaler and spacer device both easier to
      administer (78%, P = 0.007) and more convenient to take (76%, P = 0.008) than
      nebulized budesonide. In addition, cost per patient analysis showed that
      nebulized budesonide was from 1.7 to 3.5 times more expensive than FP.

PMID- 9519236
TI  - Pulmonary cryptococcoma with CD4 lymphocytopenia and meningitis in an HIV
      negative patient.

PMID- 9519237
TI  - Reactive amyloidosis in a patient with Mycobacterium simiae pulmonary infection.

PMID- 9519238
TI  - The menstrual cycle of the spider monkey (Ateles geoffroyi).
AB  - The ovarian cycles of four adult female spider monkeys (Ateles geoffroyi) were
      followed daily throughout 30 days by means of vaginal swabs and blood samplings.
      Cytological analyses of the vaginal swabs and radioimmunoassay determination of
      the daily levels of estradiol-17 beta (E2) and progesterone (P4) wer done in
      order to classify the kind of ovarian cycle of this species. Our results show
      that Ateles geoffroyi females display menstrual cycles of about 24 days on
      average. By comparison with the well-known menstrual cycles of women, apes, and
      Old World monkeys, the four distinctive cytological phases (bleeding, follicular,
      periovulatory, and luteal) could be recognized; mid-cycle E2 peaks followed by
      mid-luteal increases of the same hormone were present in all four females. P4
      levels were higher after the E2 peak, although both hormones were present
      throughout the cycles. Also, age-dependent features, hormone profiles, and
      changes in menstrual phases lengths were detected.

PMID- 9519240
TI  - Social context affects how rhesus monkeys explore their environment.
AB  - This study reports on social modulation of exploratory behavior and response to
      novelty by members of a captive rhesus monkey colony. The group was trained to
      split in half, with one subgroup composed of dominant members only, the other of
      subordinates. The animals were then presented the same initially novel stimuli
      (i.e., sand-filled metal boxes containing hidden food items) in two social
      contexts differing in hierarchical composition. In a combined context, all group
      members (i.e., both subgroups together) were simultaneously presented the
      stimuli. In a split context, only members of the top or bottom half of the group
      (i.e., each subgroup in turn) was independently presented the stimuli.
      Subordinates responded similarly to dominant animals in the combined context but
      differently in the split context, where they were far more hesitant. Rank-related
      differences were evident in the way animals used their home compound and in their
      approach and responsiveness toward the stimuli. These findings show that social
      context influences how animals explore novel situations, possibly reflecting
      different social roles or status effects on the perception of social structure.
      Also, despite the complexity of primate social relationships, the separation
      technique produced no permanent or adverse effects on the social integrity of the
      group. This study shows that manipulating the social environment through
      separation training can be a powerful tool for assessing contextual influences on
      behavior.

PMID- 9519239
TI  - Growth and reproduction in captive tufted capuchins (Cebus apella).
AB  - We present data on weight and reproduction from a colony of tufted capuchins
      monkeys (Cebus apella) over a 12 year period. The data constitute a normative
      record for this species. Weight at birth averages 210 g, and infants gain weight
      rapidly. Females typically first conceived just after their fifth birthday, and
      males were fertile by 4 years, 5 months. Interbirth intervals average 576 days.
      Eighty-seven percent of live-born infants survived past 6 months. Three of eight
      live-born infants that died prior to 6 months succumbed from trauma inflicted by
      cage mates.

PMID- 9519241
TI  - Use of leaves as cushions to sit on wet ground by wild chimpanzees.
AB  - A new type of tool use, leaf cushion, by wild chimpanzees (Pan troglodytes verus)
      at Bossou, Guinea, was found. We report two cases: one is indirect evidence; the
      other is direct observation of a chimpanzee who used the tool. Both cases
      indicate that chimpanzees used a set of leaves as a cushion while sitting on wet
      ground. Chimpanzees at Bossou show various kinds of tool use, some of which are
      unique to the community. Most of these behavioral patterns are substance tool use
      for obtaining food, as at other study sites. The use of leaves as a cushion adds
      to the few instances of nonsubstance, elementary technology seen used by wild
      chimpanzees.

PMID- 9519242
TI  - Arthur S. Kling: pioneer of the primate social brain.

PMID- 9519243
TI  - Brain 5-HT1A receptor autoradiography and hypothermic responses in rats bred for
      differences in 8-OH-DPAT sensitivity.
AB  - Three rat lines were selectively bred for high (HDS), random (RDS), or low (LDS)
      hypothermic responses to the specific 5-HT1A receptor agonist 8-OH-DPAT. Forty
      five minutes after 8-OH-DPAT administration (0.5 mg/kg), body temperatures
      dropped 3-5 degrees C in HDS rats, yet this dose produced only about 1.2 degrees
      C and 0.7 degree C drops in RDS and LDS rats, respectively. To investigate the
      relationship of body temperature of 5-HT1A receptor binding sites,
      autoradiographic analyses of [3H]8-OH-DPAT binding to 5-HT1A receptors in brains
      of these rats were conducted. Significant differences in binding were found in
      specific limbic cortical projection sites, with the HDS line having the greatest
      density of sites. Body temperature responses correlated significantly with [3H]8
      OH-DPAT receptor binding in only a few areas of frontal cortex. Binding in many
      other brain regions, including the anterior and posterior hypothalami (regions
      long associated with body temperature regulation) and the raphe showed no
      significant differences among the lines. [3H]Ketanserin binding to cortical 5-HT2
      receptors did not differ among the lines, except in the cingulate and superficial
      frontal cortices where HDS exhibited higher binding. These data suggest that
      differences in 5-HT1A receptor number may contribute to the exaggerated
      hypothermic response to 8-OH-DPAT in HDS rats. These studies also suggest that
      genetic regulation of receptor density may be brain region specific which should
      encourage future studies of the mechanisms of 5-HT1A receptor activity in brain
      and the action of drugs affecting this receptor.

PMID- 9519244
TI  - Castration decreases extracellular, but increases intracellular, dopamine in
      medial preoptic area of male rats.
AB  - Dopamine (DA) is released in the medial preoptic area (MPOA) of male rats in the
      presence of a female, and it facilities male sexual behavior. Castration blocks
      the DA response to a female and the male's ability to copulate. The present
      experiments examined the effects of castration on (1) basal levels of
      extracellular DA in the MPOA, using the no net flux microdialysis technique, (2)
      the response of extracellular DA to amphetamine, and (3) tissue levels of DA.
      Castrated rats had lower basal levels of extracellular DA in the MPOA, compared
      with gonadally intact rats; in vivo recovery, a measure of uptake, was not
      different. This suggests that castration decreases DA release in basal
      conditions, as well as in response to a female. However, systemic amphetamine
      injections, which induce DA release, resulted in greater DA release in castrates.
      Finally, tissue levels of DA were higher in the MPOA, the caudate-putamen and the
      bed nucleus of stria terminalis of castrates. These data suggest that DA
      synthesis and storage in the MPOA are normal, or even enhanced, in castrates, and
      uptake is not altered. The deficit in extracellular levels appears to be related
      to release, perhaps due to decreased nitric oxide.

PMID- 9519245
TI  - Effects of the opioid antagonist naltrexone on feeding induced by DAMGO in the
      central nucleus of the amygdala and in the paraventricular nucleus in the rat.
AB  - The paraventricular nucleus of the hypothalamus (PVN) and the central nucleus of
      the amygdala (CNA) are two forebrain structures which are important in regulation
      of ingestive behavior. DAMGO is one of the most reliable and potent mu-selective
      opioid ligands that increases feeding in both of these brain nuclei.
      Administration of naloxone, an opioid antagonist, into the CNA prior to DAMGO
      blocks DAMGO-induced increases in food intake. The effect of this drug
      combination on food intake has not been evaluated in the PVN. However, intra-PVN
      injection of naloxone decreases deprivation and NPY-induced feeding. It has been
      suggested that CNA may modulate activity of midbrain and caudal brainstem centers
      via the hypothalamus. Based on these data, we evaluated whether an opioid-opioid
      interaction is present between the CNA and PVN which might affect feeding
      behavior. To test this, rats were doubly cannulated with 1 cannula placed in the
      PVN and 1 cannula in the CNA, allowing for co-administration of the opioid
      agonist into the PVN and the opioid antagonist into the CNA, and vice versa. CNA
      DAMGO increased feeding more than two-fold as compared to the vehicle-injected
      rats. When doses of 10, 12.5 and 25 micrograms of naltrexone (NTX) were injected
      into the PVN, CNA DAMGO no longer increased food intake above control levels. In
      the reverse situation, PVN DAMGO also increased food intake above control levels.
      However, when NTX was administrated unilaterally into the CNA at a relatively
      high dose (25 micrograms) or bilaterally (12.5 micrograms), PVN DAMGO-induced
      feeding was not altered. This suggests that an opioid-opioid signaling pathway
      exists from the CNA to the PVN which influences feeding via mu opioid receptors,
      whereas such a pathway from the PVN to the CNA does not seem to exist.

PMID- 9519246
TI  - Central renin injections: effects on drinking and expression of immediate early
      genes.
AB  - This study investigated the drinking response and the expression of Fos- and Egr
      1-immunoreactivity (Fos-ir; Egr-1-ir) in the brain induced by endogenous
      angiotensin generated by intracerebroventricular (i.c.v.) injection of renin.
      Renin induced Fos-ir in the subfornical organ (SFO), median preoptic (MnPO),
      supraoptic and paraventricular nuclei (SON and PVN), area postrema (AP), nuclei
      of the solitary tract (NTS) and lateral parabrachial nuclei (LPBN). Renin-induced
      Egr-1-ir exhibited a similar pattern of distribution as that observed for Fos-ir.
      The dose of i.c.v. renin that induced expression of immediate early gene (IEG)
      product immunoreactivity also produced vigorous drinking. When renin-injected
      rats were pretreated with captopril, an angiotensin converting enzyme inhibitor,
      drinking was blocked. With the same captopril pretreatment, both Fos- and Egr-1
      ir in the SFO, MnPO, SON, PVN, AP and LPBN were also significantly reduced.

PMID- 9519247
TI  - Increase of glucose transporter densities (Glut1 and Glut3) during chronic
      administration of nicotine in rat brain.
AB  - Chronic infusion of nicotine is known to result in a distinct pattern of
      increases in local cerebral glucose utilization (LCGU). The present study
      addresses the question whether this increase in LCGU is paralleled by (1) a local
      increase in Glut1 and/or Glut3 glucose transporter densities and (2) a local
      increase in capillary density in the brain. Nicotine was infused by osmotic
      minipumps for one week. In cryosections of rat brains local densities of Glut1
      (vascular) and Glut3 (neuronal) glucose transporters were measured by
      immunoautoradiographic methods whereas local capillary densities were determined
      by an immunofluorescent method. Densities of glucose transporters Glut1 and Glut3
      were increased in 12 of the 27 structures investigated. Glut1 was elevated in
      four additional structures and Glut3 in two more structures. Comparison of the
      changes in transporter densities with the changes of LCGU measured in a previous
      study during chronic nicotine infusion showed that LCGU was also elevated in most
      of these structures. In contrast, capillary density remained unchanged in all
      structures investigated. It is concluded that one week of nicotine infusion is
      sufficient to raise the densities of Glut1 and Glut3 glucose transporters
      predominantly in those structures in which LCGU is elevated. The unchanged
      capillary density under these conditions indicates an increased density of Glut1
      transporters per capillary.

PMID- 9519248
TI  - Ethanol inhibition of NMDA currents in acutely dissociated medial septum/diagonal
      band neurons from ethanol dependent rats.
AB  - The effect of acutely applied ethanol and the impact of chronic ethanol
      treatment, sufficient to induce tolerance and physical dependence, on N-methyl-D
      aspartate (NMDA) receptor function were studied in acutely isolated neurons from
      the medial septum/diagonal band (MS/DB) of adult rats using whole cell, patch
      clamp electrophysiology. There was a small positive correlation for capacitance
      and current amplitude activated by 100 microM NMDA for all groups. Also, cell
      membrane capacitance was significantly smaller for Ethanol Dependent
      (approximately 80-84%) than either Naive or Control cells. Therefore NMDA
      activated responses were normalized for capacitance (current density, pA/pF)
      across all three groups. NMDA-activated (30-1000 microM) responses were
      significantly larger in cells from Control and Ethanol Dependent rats relative to
      those from Naives. In addition, estimated maximal responses were significantly
      larger for Ethanol Dependent cells, compared to either Control or Naive,
      respectively, while EC50s and slopes were not significantly different. Acute 60
      mM ethanol significantly inhibited responses to 100 microM NMDA in all three
      groups, however, mean ethanol inhibition was 12-25% smaller after ethanol
      dependence. There was no evidence of acute tolerance to ethanol inhibition for
      any group, but examination of patterns of inhibition for individual neurons
      showed a few cells were resistant to ethanol or exhibited progressive loss of
      ethanol inhibition. These results suggest that NMDA receptor function in acutely
      isolated MS/DB neurons is increased following in vivo chronic ethanol treatment,
      and shows resistance to acute ethanol inhibition suggesting NMDA receptor
      mediated cellular tolerance.

PMID- 9519249
TI  - Calretinin-immunoreactive elements in the retina and optic tectum of the frog,
      Rana esculenta.
AB  - The frog retina contains numerous 28 kDa calbindin positive elements in its every
      layer. At the same time, parvalbumin has been observed only in a few elements in
      the visual system of amphibian species, whilst calretinin immunoreactivity could
      be detected in salamander retina and the optic tectum of tench. However, the
      presence and distribution of calretinin have been described to date neither in
      the retina nor in the other parts of the visual system of anurans. Therefore, the
      aim of this study is to describe the calretinin immunoreactive elements in the
      retina and the optic tectum of the frog and to establish whether or not the
      expression of this calcium-binding protein is transmitter-related and/or cell
      type specific in these parts of the central nervous system. In the retina,
      numerous bipolar cells showed calretinin immunoreactivity. The axon terminals of
      the bipolar cells branched in both the OFF and ON sublayers of the inner
      plexiform layer. The few labeled amacrine cells were larger than 10 microns in
      diameter. Over 50% of the cells in the ganglion cell layer contained calretinin.
      The labeled cells in the ganglion cell layer were of usually 16-22 microns in
      diameter, although a few smaller cells were also seen. Accordingly, many optic
      fibers were also labeled. In colocalization experiments, gamma-aminobutyric acid
      and calretinin were found in partially overlapping amacrine cell populations,
      cells with the former marker being much more numerous. At the same time, all the
      gamma-aminobutyric acid positive bipolar cells also contained calretinin. Most of
      the calretinin positive neurons in the ganglion cell layer however were only
      single-labeled. Axons of ganglion cells terminated in B, C and F sublayers of
      layer 9 in the optic tectum. Local tectal neuron populations in layer 4, 6, 8 and
      9 were also labeled and a few calretinin positive cells were detected also in
      layer 2. Approximately 10% of the tectal cells were found to be immunoreactive
      for calretinin. Layer 4 and 6 cells were mostly large pear-shaped neurons while
      cells in the 8th layer were small pear-shaped and ganglion cells labeled too.
      Coexistence of gamma-aminobutyric acid and calretinin was characteristic in cells
      of the upper tectal layers while they were not detected in neurons of deep layers
      of the tectum. After monocular enucleation, contralateral to the removed eye,
      calretinin-immunoreactivity disappeared almost completely from F sublayer and
      became less pronounced in sublayers B and C after 90 days. Calretinin
      immunoreactivity remained mostly unchanged in local tectal cells. The results
      show that, although its function remains undetermined, calretinin is the major EF
      hand calcium-binding protein in the frog retina and optic tectum.

PMID- 9519250
TI  - Suprachiasmatic nucleus: role in circannual body mass and hibernation rhythms of
      ground squirrels.
AB  - Female golden-mantled ground squirrels that sustained complete ablation of the
      suprachiasmatic nucleus (SCNx) were housed pre- and post-operatively at 23
      degrees C and then at 6.5 degrees C for 5-7 yr. SCNx and control animals held at
      the higher temperature manifested circannual rhythms (CARs) in body mass. In
      contrast, body mass CARs were not expressed in 50% of SCNx squirrels during cold
      exposure; rhythm amplitude was reduced to 25-40% of pre-operative values and the
      interval between successive peaks in body mass fell outside the circannual range.
      Unlike normal squirrels that hibernate for about 6 months during each circannual
      cycle, these SCNx squirrels expressed bouts of torpor nearly continuously
      throughout 2.5 yr of cold exposure. Body mass increases were often observed
      during hibernation--a phenomenon never observed in control animals. The remaining
      SCNx squirrels that did not hibernate continuously displayed CARs in body mass
      within the normal range. The effects of SCN ablation on body mass rhythms
      presumably are related to disrupted patterns of hibernation, food intake, and
      metabolism. The SCN, which sustains neural and metabolic activity at low tissue
      temperatures, may exert greater influence on thermoregulation and metabolism
      during the hibernation season than at other times of year, thereby accounting for
      the greater effect of SCN ablation in squirrels maintained at low ambient
      temperatures.

PMID- 9519251
TI  - Participation of AT1 and AT2 receptor subtypes in the tonic inhibitory modulation
      of baroreceptor reflex response by endogenous angiotensins at the nucleus tractus
      solitarii in the rat.
AB  - We evaluated the endogenous action of angiotensin II (AII) and its active
      metabolite, angiotensin III (AIII), at the nucleus tractus solitarii (NTS) in the
      modulation of baroreceptor reflex (BRR) response, and the subtype(s) of
      angiotensin receptors involved in this process. Adult, male Sprague-Dawley rats
      that were anesthetized and maintained with pentobarbital sodium were used.
      Bilateral microinjection of AII or AIII (10, 20 or 40 pmol) into the NTS
      significantly and dose-dependently suppressed the BRR response, which was evoked
      by transient hypertension induced by phenylephrine (5 micrograms/kg, i.v.). The
      suppressive effect of AII (40 pmol) was reversed by co-administration of the non
      peptide AT1 receptor antagonist, losartan (1.6 nmol), but only partially by the
      non-peptide AT2 receptor antagonist, PD-123319. On the other hand, both
      angiotensin receptor antagonists appreciably reversed the depressive action of
      AIII (40 pmol). Blocking the endogenous activity of the angiotensins by
      microinjection into the bilateral NTS of losartan (1.6 nmol) or PD-123319 (1.6
      nmol) elicited a significant enhancement of the BRR response. An interruption of
      the conversion of AII to AIII with the aminopeptidase A inhibitor, amastatin (3.3
      nmol), attenuated, but did not eliminate, the AII-induced inhibition of the BRR
      response. We conclude that whereas the endogenous AIII may exert a tonic
      inhibitory modulation on the BRR response by acting on both the AT1 and AT2
      receptor subtypes, the same action of the endogenous AII engaged only the AT1
      receptor subtype at the NTS. Furthermore, at least part of the suppressive action
      of AII may result from its metabolic conversion to AIII.

PMID- 9519252
TI  - Lithium inhibits the reverse tolerance and the c-Fos expression induced by
      methamphetamine in mice.
AB  - To elucidate the mechanism of psychostimulant-induced reverse tolerance, the
      effects of lithium on ambulatory activity and cerebral c-Fos protein expression
      were investigated in mice injected with methamphetamine (2 mg/kg, s.c., 1-5
      times). The ambulatory activity enhanced by either acute or chronic
      methamphetamine injection was delayed or diminished by LiCl pretreatment (170
      mg/kg, s.c., 1 h before methamphetamine). The c-Fos expression in the dorsal
      lateral geniculate nucleus and in the striatum was significantly increased by
      acute but not chronic injection of methamphetamine, and the increases were
      significantly suppressed by LiCl pretreatment. Although how the Li-sensitive c
      Fos expressions in the dorsolateral geniculate nucleus and striatum are related
      to methamphetamine-induced behavioral excitation is unclear, these results
      suggest that lithium at least functionally interferes with the formation of the
      state of reverse tolerance to methamphetamine in the mouse.

PMID- 9519253
TI  - Multiple pathways for regulation of the KCl-induced [3H]-GABA release by
      metabotropic glutamate receptors, in primary rat cortical cultures.
AB  - In rat cortical primary cultures, group II- and III-metabotropic glutamate
      receptor-selective agonists concentration-dependently reduced KCl-induced
      [3H]GABA release, with IC50 values of 11 nM for LY354740, 80 nM for L(+)-2-amino
      4-phosphonobutyric acid (L-AP4), 180 nM for DCG-IV, and 330 nM for L-SOP. The
      group II antagonists, LY341495 and EGLU, reversed the effect of LY354740, and the
      group III antagonist MTPG reversed the effect of L-AP4. In the presence of omega
      conotoxin GVIA, LY354740 inhibited the remaining [3H]GABA release, whereas L-AP4
      was inactive. In contrast, in the presence of nifedipine, L-AP4 inhibited the
      remaining [3H]GABA release, but LY354740 was no longer active. The PKA inhibitor,
      H89, blocked the effects of both L-AP4 and LY354740, whereas the PKC inhibitor Ro
      31-8220 blocked only the effect of LY354740. Both Ro 31-8220 and H89 reduced the
      [3H]GABA release to 60% of control. In whole-cell, voltage-clamp experiments,
      LY354740 and L-AP4 inhibited voltage-gated calcium channel currents with IC50
      values of 28 nM and 22 microM, respectively. The results suggest that, in these
      cells, KCl-induced [3H]GABA release is modulated by two different mechanisms, one
      involving group II receptors and a direct control of the Ca2+ channel activity,
      and the other mediated by group III receptors and possibly involving a regulation
      located downstream of the Ca2+ channel activation.

PMID- 9519254
TI  - Effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in goldfish cerebellum:
      neurochemical and immunocytochemical analysis.
AB  - 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administered in goldfish for
      3 consecutive days (10 mg kg-1 i.p.), caused cerebellar disappearance of dopamine
      hydroxylase (DBH) immunoreactive fibres, whereas the noradrenergic cell bodies
      located in the medulla oblongata appeared intact. This effect was coupled with
      marked decreases in cerebellar noradrenaline (NA) and dopamine (DA) levels. An
      increase of immunostaining for glial fibrillary acidic protein (GFAP) was also
      observed. In the cerebellum of MPTP-treated fish, the contents of glutamate and
      GABA were significantly reduced, whereas glutamine was strongly increased. These
      modifications were concomitant with a significant increase of glutamine
      synthetase (GS) activity, whereas glutamic acid decarboxylase (GAD) activity was
      decreased. No changes in choline acetyltransferase (ChAT) and ornithine
      decarboxylase (ODC) activities were observed. High affinity uptake of glutamate
      and GABA was strongly reduced. Pretreatment of fish with either the monoamine
      oxidase inhibitor pargyline or the catecholamine (CA) uptake blocker mazindol
      largely prevented such modifications. The NMDA-sensitive glutamate receptor
      uncompetitive antagonist, dizocilpine maleate (MK-801), failed to protect against
      MPTP-induced damage. In conclusion, the neurotoxic effects of MPTP in goldfish
      cerebellum appear to be not specific against catecholaminergic terminals and
      could promote astrocytic reactions.

PMID- 9519255
TI  - Brainstem neurons projecting to the rostral ventral respiratory group (VRG) in
      the medulla oblongata of the rat revealed by co-application of NMDA and biocytin.
AB  - Groups of neurons in the medulla and pons are essential for the rhythm
      generation, pattern formation and modulation of respiration. The rostral Ventral
      Respiratory Group (rVRG) is thought to be a crucial area for rhythm generation.
      Here we co-applied biocytin and NMDA in the rVRG to label retrogradely brainstem
      neurons reciprocally connected to a population of inspiratory neurons in the rat
      rVRG. The procedure excited rVRG neurons in multi-unit recordings and led to a
      Golgi-like labelling of distant cells presumably excited by efferents from the
      rVRG. Injection of biocytin without NMDA did not label neurons in distant
      structures. Several brainstem ipsi- and contralateral structures were found to
      project to the rVRG, but three major respiratory-related structures, the nucleus
      of the solitary tract (NTS), the parabrachialis medialis and Kolliker-Fuse nuclei
      (PB/KF) and the caudal VRG, which are known to project bilaterally to the rVRG,
      were exclusively labelled ipsilaterally, suggesting an ipsilateral excitation of
      these structures by the rVRG. The pathways of efferent axons from labelled
      neurons in the rVRG were traced rostrally towards the pons and caudally to the
      spinal cord. Terminal axonal arborizations were seen in the same regions where
      retrogradely filled neurons were found as well as in a few other motor nuclei
      (the dorsal vagal motor nucleus and XII nucleus). Moreover, in the NTS and the
      PB/KF, efferent terminal varicosities were seen closely apposed to the soma and
      proximal dendrites of labelled neurons, suggesting monosynaptic connections
      between the rVRG and these nuclei.

PMID- 9519256
TI  - Spontaneous long-term remyelination after traumatic spinal cord injury in rats.
AB  - The capability of the central nervous system to remyelinate axons after a lesion
      has been well documented, even though it had been described as an abortive and
      incomplete process. At present there are no long-term morphometric studies to
      assess the spinal cord (S.C.) remyelinative capability. With the purpose to
      understand this phenomenon better, the S.C. of seven lesionless rats and the S.C.
      of 21 rats subjected to a severe weight-drop contusion injury were evaluated at
      1, 2, 4, 6, and 12 months after injury. The axonal diameter and the myelination
      index (MI = axolemmal perimeter divided by myelinated fiber perimeter) were
      registered in the outer rim of the cord at T9 SC level using a transmission
      electron microscope and a digitizing computer system. The average myelinated
      fiber loss was 95.1%. One month after the SC, 64% of the surviving fibers were
      demyelinated while 12 months later, only 30% of the fibers had no myelin sheath.
      The MI in the control group was 0.72 +/- 0.07 (X +/- S.D.). In the experimental
      groups, the greatest demyelination was observed two months after the lesion (MI =
      0.90 +/- 0.03), while the greatest myelination was observed 12 months after the
      injury (MI = 0.83 +/- 0.02). There was a statistical difference (p < 0.02) in MI
      between 2 and 12 months which means that remyelination had taken place.
      Remyelination was mainly achieved because of Schwann cells. The proportion of
      small fibers (diameter = 0.5 micron or less) considered as axon collaterals,
      increased from 18.45% at 1 month to 27.66% a year after the contusion. Results
      suggest that remyelination is not an abortive phenomenon but in fact a slow
      process occurring parallel to other tissue plastic phenomena, such as the
      emission of axon collaterals.

PMID- 9519257
TI  - Inflammation-induced Fos protein expression in the rat spinal cord is enhanced
      following dorsolateral or ventrolateral funiculus lesions.
AB  - Previous studies have shown an enhanced expression of Fos protein-like
      immunoreactivity in the lumbar spinal cord of rats with complete spinal
      transection following persistent hindpaw inflammation. To further locate the
      spinal pathways responsible for these effects, we compared the inflammation
      evoked Fos expression in rats with bilateral lesions of the dorsolateral (DLFX)
      or ventrolateral (VLFX) funiculus, and with rats with a sham operation. The
      results indicate that the number of Fos-labeled neurons was significantly
      increased in all laminae of the dorsal horn ipsilateral to the inflamed hindpaw
      and in contralateral deep dorsal horn in both DLFX and VLFX rats compared to sham
      operated rats. Moreover, when comparing DLFX and VLFX rats, in the ipsilateral
      spinal cord, DLFX resulted in more Fos expression in the deep dorsal horn; in
      contrast, a larger number of Fos-labeled cells in superficial laminae was
      observed in VLFX rats. These results suggest that modulatory systems, which
      descend in both DLF and VLF pathways, mediate the enhanced net descending
      nociceptive inhibition after persistent inflammation, although the supraspinal
      sites of origin of each pathway are likely functionally diverse.

PMID- 9519258
TI  - Glutamate receptors in dysplasic cortex: an in situ hybridization and
      immunohistochemistry study in rats with prenatal treatment with
      methylazoxymethanol.
AB  - Injection of the antimitotic drug methylazoxymethanol (MAM) in the pregnant rat
      at E14 leads in the offsprings to a severe malformation with microcephaly and
      cortical heterotopiae in the white matter and in the CA1 field of the
      hippocampus. These animals suffer cognitive and epileptic disorders. Since these
      pathologies have been associated with glutamatergic transmission abnormalities,
      we have examined by in situ hybridization and immunohistochemistry the
      distribution and expression levels of several glutamate receptors subunits in
      these rats. Examination of the GluR2 flip and flop, NR1, NR2A and NR2B subunit
      gene transcripts showed a qualitatively similar distribution in both the
      neocortex and hippocampus of MAM and control rats. Quantitative analysis revealed
      an altered proportion of the GluR2 flip and flop subunits in the CA1 region of
      MAM animals as compared to controls. Moreover, a 26% reduction in the expression
      of the NR1 subunit and a 40% increase in the expression of the GluR2 flip subunit
      were noted in cortical heterotopiae, as compared to the adjacent neocortex.
      Immunostaining for GluR2/3, NR1 or NR2 showed, in both MAM and control animals,
      that glutamate receptors were mainly concentrated in the soma and dendrites of
      neocortical and hippocampal pyramidal cells, including in heterotopiae, and in
      the apical dendrites of hippocampal granule cells. Abnormalities in the
      expression of glutamate receptor subtypes in cortical heterotopiae and in the
      hippocampal CA1 region could contribute to functional disorders previously
      reported in MAM animals such as memory impairments and epilepsy.

PMID- 9519259
TI  - On the reorganization of sensory hand areas after mono-hemispheric lesion: a
      functional (MEG)/anatomical (MRI) integrative study.
AB  - The topography of primary sensory cortical hand area following a monohemispheric
      lesion (sudden = stroke; progressive = neoplasm) was investigated in relationship
      with clinical recovery of sensorimotor deficits. Twenty seven patients with
      monohemispheric lesions were studied in a clinically stabilized condition.
      Functional informations from magnetoencephalography (MEG) were integrated with
      anatomical data from magnetic resonance imaging (MRI). MEG localizations of the
      neurons firing at early latencies in primary sensory cortex after separate
      stimulation of median nerve, thumb and little fingers of each hand were carried
      out. Characteristics of cerebral equivalent current dipoles (ECDs) activated by
      each contralateral stimulation, the 'hand extension' (i.e., the distance in
      millimetres between ECDs of first and fifth digits), as well as interhemispheric
      differences of the tested parameters were investigated. Finally, ECDs' locations
      were integrated with MRI. Lesions involving cortical (C) or subcortical (s.c.)
      areas receiving sensory input from the hand were often combined to increase
      interhemispheric asymmetry of the tested parameters (22% for C and 49% for s.c.
      lesions). This might be due to an activation of neuronal districts which in the
      affected hemisphere (AH) differ from those normally activated in the unaffected
      hemisphere (UH) and in the control population. Moreover, the 'hand extension' was
      enlarged on the AH--more frequently after a SC lesion--mainly due to a medial
      shift of the little finger ECD, combined to a tendency of both finger ECDs to
      shift frontally. After a C lesion, responses from the AH were often stronger than
      normal. Spatial reorganizations were also seen in the UH (7% of C and 14% of SC
      lesions). 'Hand extension' in the UH was selectively enlarged for the P30m only
      when combined with a similar enlargement in the AH. Significant interhemispheric
      asymmetries due to neuronal reorganization in the AH were associated with worse
      clinical outcomes compared to patients without asymmetries.

PMID- 9519260
TI  - Stimulation of expression of the oxytocin gene in rat supraoptic neurons at
      parturition.
AB  - We measured expression of the oxytocin gene in the supraoptic nucleus (SON)
      during pregnancy, parturition and lactation to examine its relationship to states
      of accumulation or depletion of oxytocin stores and to conditions of strong
      excitation of oxytocin neurons. The primary transcript (heterogeneous nuclear
      RNA, hnRNA) of the oxytocin gene was measured using a 3H-cDNA probe against
      intron 1 for in situ hybridisation. Autoradiographs of the SON showed the hnRNA
      as discrete clumps of silver grains within the nucleus of each neuron. The number
      of cells expressing oxytocin hnRNA did not change during pregnancy but increased
      during parturition; 10-day lactating animals showed similar increases. Oxytocin
      mRNA was also measured by in situ hybridisation using a 3H- or 35S-labelled
      oligonucleotide probe against exon C: hybridisation was seen over the cytoplasm
      of supraoptic neurons, but no differences were measured between virgin, mid
      pregnant, preparturient, parturient or 2-day lactating rats. The data suggest
      that enhanced oxytocin gene transcription is not necessary to increase oxytocin
      stores in pregnancy. However, acute stimulation of magnocellular oxytocin neurons
      at parturition, which strongly increases neuron activity and secretion, results
      in a rapid increase in the number of cells expressing oxytocin hnRNA, and
      increased expression is sustained in lactation.

PMID- 9519261
TI  - Preischemic hyperglycemia leads to rapidly developing brain damage with no change
      in capillary patency.
AB  - The present experiments were undertaken to explore whether exaggeration of
      ischemic brain damage by preischemic hyperglycemia is due to lack of capillary
      patency in the postischemic period. Normo- and hyperglycemic rats were exposed to
      10 min of forebrain ischemia. Histopathological changes were evaluated after 6
      and 16-18 h of recovery by light microscopy, and capillary patency was assessed
      at the same time points by a double-staining technique, depicting perfused and
      morphologically identifiable capillaries. The results demonstrate that some
      neuronal damage was detectable after 6 h of recirculation which was aggravated
      after 16-18 h of recirculation in hyperglycemic rats. In contrast, the degree of
      capillary patency was similar in normo- and hyperglycemic rats. In both groups
      the perfusion marker, Evans blue, perfused about 95% of all capillaries when
      injected 10 s before decapitation. Since preischemic hyperglycemia exaggerates
      brain damage without cessation of capillary perfusion the primary targets of
      hyperglycemic brain damage may not be capillaries but neurons or glial cells.

PMID- 9519263
TI  - Cerebral blood flow autoregulation following subarachnoid hemorrhage in rats:
      chronic vasospasm shifts the upper and lower limits of the autoregulatory range
      toward higher blood pressures.
AB  - We sought to determine whether chronic vasospasm following subarachnoid
      hemorrhage (SAH) would abolish the cerebral blood flow (CBF) autoregulation in
      anesthetized Sprague-Dawley rats. SAH was induced by intracisternal injection of
      autologous blood; in control animals saline was injected instead. CBF was
      measured 48 h after SAH, that is during chronic vasospasm, by laser-Doppler
      flowmetry over the frontal cortex under condition of hypertension (SAH, n = 6;
      control, n = 8) or hypotension (SAH, n = 6; control, n = 6). Hyper- and
      hypotension were induced by increasing mean arterial blood pressure (MABP)
      stepwise from 90 to 180 mmHg with phenylephrine (0.1-10 micrograms/min i.v.), or
      by decreasing it from 90 to 40 mmHg by controlled hemorrhage. An autoregulatory
      index (AI) expressed as delta CBF (%) per 10 mmHg increase or decrease in MABP
      was employed to analyze CBF response. CBF remained constant (-7 < AI < 7) at
      MABPs ranging from 60 to 130 mmHg in the control group and from 70 to 140 mmHg in
      the SAH group, showing CBF autoregulation. In the SAH group, that is, the upper
      and the lower limits of autoregulatory range were increased by 10 mmHg (p <
      0.05). SAH did not increase intracranial pressure significantly (control 9.2 +/-
      0.67 vs. SAH 10.0 +/- 1.05 mmHg, n = 5) 48 h after SAH was induced. These results
      indicate that, during chronic vasospasm, SAH does not abolish the autoregulation
      process but raises its lower and upper blood pressure limits. The capacity of
      spastic cerebral arteries to dilate in case of hypotension decreased, while their
      tolerance to hypertension increased.

PMID- 9519262
TI  - Alpha 2-adrenergic receptor activation inhibits calcitonin gene-related peptide
      expression in cultured dorsal root ganglia neurons.
AB  - Calcitonin gene-related peptide (CGRP), a potent vasodilator, is produced in
      dorsal root ganglia (DRG) neurons which extend nerves peripherally to blood
      vessels and centrally to the spinal cord. We previously reported that neuronal
      CGRP expression is significantly reduced in the spontaneously hypertensive rat
      (SHR) which could contribute to the elevated BP. Other studies suggest that the
      enhanced activity of the sympathetic nervous system in the SHR may mediate, at
      least in part, this reduction in neuronal CGRP expression via activation of alpha
      2-adrenoreceptors (alpha 2-AR) on DRG neurons. To test this hypothesis in vitro
      we employed primary cultures of adult rat DRG neurons. Neuronal cultures were
      initially exposed (24 h) to either the alpha 2-AR agonist UK 14,304 (10(-6) M) or
      vehicle; however, no changes in CGRP mRNA content or immunoreactive CGRP (iCGRP)
      release were observed. Using the rationale that in vivo DRG neurons receive a
      continuous supply of target tissue derived nerve growth factor (NGF), which
      stimulates CGRP synthesis, the cultured neurons were treated (24 h) with either
      vehicle, NGF (25 ng/ml) alone, or NGF plus UK. NGF treatment increased CGRP mRNA
      accumulation 5.5 +/- 0.9-fold (p < 0.001) and iCGRP release 2.9 +/- 0.4-fold (p <
      0.001) over control levels. The stimulatory effects of NGF were markedly
      attenuated, but not abolished, by UK (NGF + UK vs. control, CGRP mRNA, 2.9 +/-
      0.4-fold, p < 0.05; iCGRP, 1.7 +/- 0.2-fold, p < 0.05). These values were also
      significant (p < 0.05) when compared to NGF treatment alone. Experiments
      performed using the alpha 2-antagonist yohimbine confirmed that the effects of UK
      were mediated by the alpha 2-AR. These results, therefore, demonstrate that alpha
      2-AR activation attenuates the stimulatory effects of NGF on CGRP expression in
      DRG neurons.

PMID- 9519264
TI  - Sustained bombesin exposure results in receptor down-regulation and tolerance to
      the chronic but not acute effects of bombesin on ingestion.
AB  - Acute intracerebroventricular (i.c.v.) administration of bombesin (BN) reduces
      meal intake in fasted rats. The overall objective of the present study was to
      determine the behavioral and other ingestive effects of prolonged central
      administration of BN. In the first experiment, we characterized the effects of 8
      day sustained central administration of BN (0, 0.01, 0.05, 0.1 and 5
      micrograms/0.5 microliter/h) or its antagonist (BIM-26226; 0, 0.005, 0.05, 0.5
      and 5.0 micrograms/0.5 microliter/h), in free feeding rats. Each dose was
      delivered over 48 h, in an ascending sequence. At the higher doses, the BN
      exposed rats consumed significantly less food whereas those exposed to the BN
      antagonist ingested significantly more food than the controls (saline exposed),
      during the dark phase. Due to the limited 48-h exposure to these higher doses, we
      further investigated the effects of more sustained BN exposure. Thus BN was
      infused over a 7-day period, at a rate of 0.25 microgram BN/0.5 microliter/h. In
      this latter study, we determined the effects of sustained BN exposure on a) daily
      spontaneous ingestive pattern, b) the rat's ingestive and other behavioral
      responses to a subsequent acute BN (i.c.v.) challenge and, c) BN receptor binding
      profile in various brain regions. Over the initial 2 days of chronic infusion, BN
      significantly suppressed spontaneous ingestion, and this effect dissipated by 72
      h. Upon acute challenge with bolus injection of BN (0.25 microgram; i.c.v.), both
      chronically BN-treated and control rats responded by decreased feeding and
      enhanced grooming behaviors. In terms of effects at the receptor level, chronic
      BN exposure resulted in significant down-regulation (reduced BN/GRP receptor
      density) at the PVN and the hippocampal dentate gyrus. These findings represent
      the first demonstration of concomitant behavioral and receptor based changes
      consequent to sustained exposure to BN. These data suggest that tolerance to
      feeding suppressant effects of BN develops gradually, which in part may be
      mediated by down-regulation of BN/GRP receptors at specific brain loci. Our
      results also suggest that despite the development of tolerance to the chronic or
      sustained effects of BN exposure, animals still respond robustly to acute
      fluctuations in peptide levels.

PMID- 9519265
TI  - Eliprodil, a non-competitive, NR2B-selective NMDA antagonist, protects pyramidal
      neurons in hippocampal slices from hypoxic/ischemic damage.
AB  - The N-methyl-D-aspartate (NMDA) subtype of glutamate receptor is one pathway
      through which excessive influx of calcium has been suggested to trigger ischemia
      induced delayed neuronal death. NMDA receptors are heterooligomeric complexes
      comprised of both NR1 and NR2A-D subunits, in various combinations. NR2B
      containing NMDA complexes exhibit larger, more prolonged conductances than those
      lacking this subunit. We tested the ability of the non-competitive, NR2B
      selective NMDA antagonist eliprodil to (a) protect synaptic transmission in in
      vitro hippocampal slices from hypoxia, and (b) reduce ischemic delayed neuronal
      death in hippocampal organotypic slice cultures. Eliprodil markedly improved the
      recovery of Schaffer collateral-CA1 excitatory postsynaptic potentials following
      a 15 min hypoxic insult, with an EC50 of approximately 0.5 microM. In contrast to
      this functional protection, eliprodil did not reduce delayed death of CA1
      pyramidal neurons in organotypic hippocampal slice cultures treated with severe
      hypoxia plus hypoglycemia, though it did potently protect CA3 pyramidal neurons
      in the same cultures. These data indicate that NMDA receptors containing NR2B
      subunits may play a role in long-term recovery of hippocampal synaptic function
      following ischemia/hypoxia. Furthermore, the selective protection of CA3, but not
      CA1, pyramidal neurons suggests that NR2B-containing NMDA receptors may
      preferentially contribute to an excitotoxic component of ischemia-induced delayed
      neuronal death.

PMID- 9519266
TI  - Methamphetamine-induced alterations in dopamine transporter function.
AB  - Repeated methamphetamine (METH) administration has been shown to produce
      differing neurochemical as well as behavioral effects in rats. This study was
      designed to examine the effects of acute and chronic METH exposure on uptake and
      release of [3H]dopamine (DA) in cultured midbrain dopamine neurons to determine
      if persistent neuronal adaptations ensue. In addition, we have assessed DA D2
      receptor function to determine if chronic METH alters this receptor. Fetal
      midbrain cultures were exposed to METH (1, 10 microM) for 5 days and dopaminergic
      function examined 1 or 7 days after drug removal. The ability of METH to release
      [3H]DA was compared to other releasing agents as well as several potent uptake
      inhibitors. Chronic exposure to a release-promoting concentration of METH
      resulted in either no change or a reduction in [3H]DA release upon subsequent
      METH challenge. Pretreatment with METH was also found to cause a decrease in the
      Bmax for [3H]raclopride binding, suggesting that persistently elevated DA levels
      cause a downregulation of DA D2 receptors. Examination of transporter kinetics
      utilizing initial velocity of uptake revealed that METH treatment caused a
      significant decrease in affinity (K(m)) for the substrate (DA), while not
      altering the maximal velocity of uptake (Vmax). Binding studies with [125I]RTI-55
      revealed that there was no alteration in either the Bmax or Kd for this ligand,
      suggesting that the changes induced by METH treatment are due to alterations in
      K(m) and not in the number of DA transport sites. The results from these studies
      indicate that METH treatment produces a modification in transporter function
      which may be associated with both the altered uptake and release of [3H]DA. These
      changes have broad implications for the regulation of transporter activity not
      only because of the relevance to pre-synaptic mechanisms controlling
      neurotransmission, but also to the importance of the neuronal adaptation that
      occurs in response to chronic METH exposure.

PMID- 9519267
TI  - Dopamine release in the nucleus accumbens by hypothalamic stimulation-escape
      behavior.
AB  - It is known that lateral hypothalamic stimulation or self-stimulation can release
      dopamine in the nucleus accumbens (NAc). The present experiment illustrates that
      an aversively motivated behavior can also do this. Rats were prepared with
      microdialysis probes in the NAc and electrodes in the lateral hypothalamus (LH)
      or medial hypothalamus (MH). Automatic stimulation of the LH increased
      extracellular dopamine in the NAc 30% as reported earlier. The animals would
      perform both self-stimulation to turn the current on and stimulation-escape to
      turn it off, suggesting a combination of reward and aversion. Escape responding
      increased extracellular dopamine (DA) 100%, even though there was less total
      stimulation. Automatic stimulation of the MH did the opposite of the LH by
      decreasing accumbens dopamine (-20%), and the animals would only perform
      stimulation-escape, indicative of pure aversion. But again, extracellular DA in
      the NAc increased 100% during escape responding. Thus DA can be released during
      negative reinforcement when an animal's behavior is reinforced by escape from
      lateral or medial hypothalamic stimulation. This suggests that DA release was
      correlated with stimulation-escape behavior, rather than the aversiveness of
      automatic stimulation.

PMID- 9519268
TI  - Serotonin regulates synaptic connections in the dentate molecular layer of adult
      rats via 5-HT1a receptors: evidence for a glial mechanism.
AB  - The present study sought to verify effects of 5-HT on synaptic density at the
      ultrastructural level, to determine whether the 5-HT1a receptor is important for
      the maintenance of synaptic connections and to obtain evidence implicating S100
      beta in the apparent neurotrophic actions of 5-HT. Reduction of hippocampal 5-HT
      with para-chloroamphetamine (PCA) resulted in a significant decline in the
      synaptic density of the dentate molecular layer. Reduction of norepinephrine with
      DSP-4 produced a slight decrease in the number of molecular layer synapses, but
      this difference was not statistically different from control values. 5-HT1a
      antagonist treatment resulted in a decline in synaptic density comparable to that
      observed following PCA treatment. These observations suggest that 5-HT functions
      to maintain synaptic connections in the dentate molecular layer via a 5-HT1a
      mechanism. To determine whether the change in synaptic density was due to the
      action of 5-HT on neuronal receptors or astrocytic receptors, a monoclonal
      antibody against S100 beta was infused into the lateral ventricle for seven days.
      Controls received infusions of normal goat serum. Half of the rats from the anti
      S100 beta and control groups also received daily injections of NAN-190. Anti-S100
      beta infusion resulted in a significant (p < 0.01) decrease in synapses compared
      to serum controls. Concomitant NAN-190 administration did not enhance synapse
      loss in the anti-S100 beta group. The results of this study suggest that the
      maintenance of synaptic connections in the dentate molecular layer is influenced
      by S100 beta levels that are controlled by 5-HT stimulation of astrocytic 5-HT1a
      receptors.

PMID- 9519269
TI  - NMDA receptor activation during status epilepticus is required for the
      development of epilepsy.
AB  - NMDA receptor activation has been implicated in modulating seizure activity;
      however, its complete role in the development of epilepsy is unknown. The
      pilocarpine model of limbic epilepsy involves inducing status epilepticus (SE)
      with the subsequent development of spontaneous recurrent seizures (SRSs) and is
      widely accepted as a model of limbic epilepsy in humans. The pilocarpine model of
      epilepsy provides a tool for looking at the molecular signals triggered by SE
      that are responsible for the development of epilepsy. In this study, we wanted to
      examine the role of NMDA receptor activation on the development of epilepsy using
      the pilocarpine model. Pretreatment with the NMDA receptor antagonist MK-801 does
      not block the onset of SE in the pilocarpine model. Thus, we could compare
      animals that experience similar lengths of SE in the presence or absence of NMDA
      receptor activation. Animals treated with MK-801 (4 mg/kg) 20 min prior to
      pilocarpine (350 mg/kg) (MK-Pilo) were compared to the pilocarpine treated
      epileptic animals 3-8 weeks after the initial episode of SE. The pilocarpine
      treated animals displayed both ictal activity and interictal spikes on EEG
      analysis, whereas MK-801-pilocarpine and control animals only exhibited normal
      background EEG patterns. In addition, MK-801-pilocarpine animals did not exhibit
      any SRSs, while pilocarpine-treated animals exhibited 4.8 +/- 1 seizures per 40
      h. MK-801-pilocarpine animals did not demonstrate any decrease in pyramidal cell
      number in the CA1 subfield of the hippocampus, while pilocarpine animals averaged
      15% decrease in cell number. In summary, the MK-801-pilocarpine animals exhibited
      a number of characteristics similar to control animals and were statistically
      significantly different from pilocarpine-treated animals. Thus, NMDA receptor
      inhibition by MK-801 prevented the development of epilepsy and interictal
      activity following SE. These results indicate that NMDA receptor activation is
      required for epileptogenesis following SE in this model of limbic epilepsy.

PMID- 9519270
TI  - Excitotoxic swelling occurs in oxygen and glucose deprived human cortical slices.
AB  - The experimental evidence linking glutamate to ischemic neuronal injury is
      derived from in vitro or in vivo animal stroke models. We, therefore, developed
      an in vitro preparation to determine whether glutamate contributes to early
      neuronal swelling in oxygen and glucose deprived (OGD) human neocortical slices.
      In order to monitor neuronal swelling, we measured extracellular tissue
      resistance in brain slices by passing constant current pulses through two
      electrodes and recording the voltage drop between them. We verified that NMDA (30
      microM) or OGD induced a rise in tissue resistance in rat neocortical slices. We
      then examined human neocortical slices from 11 patients undergoing resections for
      intractable epilepsy. Both the rodent and human neocortical slices swelled within
      10 min of OGD. In both, the glutamate antagonist dizocilpine (MK-801) reduced the
      swelling. In the rats, MK-801 (5 microM) prolonged the latency to onset of
      neuronal swelling following OGD from 7.6 +/- 0.6 min (mean +/- S.E.M., n = 16) to
      17.4 +/- 2.6 min (n = 6; p < 0.01). Other putative neuroprotective agents were
      much less effective in this paradigm. In the human slices, MK-801 again prolonged
      the latency to resistance increase from 8.6 +/- 0.4 min (n = 8) to 17.2 +/- 1.7
      min (n = 9, p < 0.01). This is the direct demonstration that glutamate receptor
      activation leads to neuronal swelling in substrate deficient human brain. These
      results, which are similar to those obtained in the rodent brain slices, help
      validate the animal slices as appropriate models for the study of OGD in human
      brain.

PMID- 9519272
TI  - Ammonia-induced depolarization of cultured rat cortical astrocytes.
AB  - Exposure of cultured rat cortical astrocytes to increased concentrations of
      ammonia has been shown to induce morphological and biochemical changes similar to
      those found in hyperammonemic (e.g., hepatic) encephalopathy in vivo. Alterations
      of electrophysiological properties are not well investigated. In this study, we
      examined the effect of ammonia on the astrocyte membrane potential by means of
      perforated patch recordings. Exposure to millimolar concentrations of NH4Cl
      induced a slow dose-dependent and reversible depolarization. At steady state,
      i.e., after several tens of minutes, the cells were significantly depolarized
      from a resting membrane potential of -96.2 +/- 0.6 mV (n = 83, S.E.M.) to -89.1
      +/- 1.6 mV (n = 7, S.E.M.) at 5 mM NH4Cl, -66.3 +/- 3.6 mV (n = 9, S.E.M.) at 10
      mM NH4Cl and -50.4 +/- 2.5 mV (n = 12, S.E.M.) at 20 mM NH4Cl, respectively. In
      order to examine the underlying depolarizing mechanisms we determined changes in
      the fractional ion conductances for potassium, chloride and sodium induced by 20
      mM NH4Cl. No significant changes were found in the fractional sodium or chloride
      conductances, but the dominating fractional potassium conductance decreased
      slightly from a calculated 0.86 +/- 0.04 to 0.77 +/- 0.04 (n = 9, S.E.M.).
      Correspondingly, we found a significant fractional ammonium ion (NH4+)
      conductance of 0.23 +/- 0.02 (n = 10, S.E.M.) which was blocked by the potassium
      channel blocker barium and, hence, most likely mediated by barium-sensitive
      potassium channels. Our data suggest that the sustained depolarization induced by
      NH4Cl depended on changes in intracellular ion concentrations rather than changes
      in ion conductances. Driven by the high membrane potential NH4+ accumulated
      intracellularly via a barium-sensitive potassium conductance. The concomitant
      decrease in the intracellular potassium concentration was primarily responsible
      for the observed slow depolarization.

PMID- 9519271
TI  - Increased levels of nerve growth factor in the urinary bladder and hypertrophy of
      dorsal root ganglion neurons in the diabetic rat.
AB  - The level of nerve growth factor (NGF) in the streptozotocin (STZ)-diabetic rat
      was measured at approximately weekly intervals after STZ induction, using an
      ELISA assay technique. In addition, the area profiles of L6-S1, and L1-L2 dorsal
      root ganglion neurons (DRG), labelled by fast blue dye injected into the bladder,
      were measured at the same weekly intervals. Compared to control animals, the
      levels of NGF rose rapidly to a maximum at one week and then slowly declined over
      the next three weeks. The areas of the DRGs increased to a peak after which they
      also started to decline. The peak increase in DRG area profiles was delayed
      relative to the peak level of bladder NGF. The data suggest that bladder NGF is
      transported retrogradely to the DRG neurons where it transforms the cell economy
      to cause an increase in size.

PMID- 9519273
TI  - Similar feeding patterns are induced by perifornical neuropeptide Y injection and
      by food deprivation.
AB  - Although hypothalamic injections of neuropeptide Y (NPY) induce robust feeding,
      there is little information about the patterns of feeding elicited by this
      peptide. To reveal these patterns, NPY (0, 8, 24, 78, 235 pmol/10 nl) was
      injected into the perifornical hypothalamus (PFH) of satiated adult male rats and
      their subsequent food intake was monitored every minute for 24 h. For comparison,
      feeding patterns were similarly observed following fasts of 0, 3, 6, 9, 12, and
      24 h. The results demonstrated that NPY and food deprivation both produced dose-
      or deprivation-dependent increases in food intake that were most evident in the
      first 6 h. The increased intakes induced by NPY were characterized by
      combinations of increased meal size and frequency, with the predominant effects
      being increases in the size of and decreased latency to eat the first meal.
      Similarly, fasting progressively increased food intake by combinations of
      increased meal size and frequency, with the predominant effects being increases
      in the size of and decreased latency to eat the first meal. These similarities
      between NPY-induced and food deprivation-induced feeding are consistent with a
      stimulatory role for endogenous NPY in deprivation-induced feeding. These
      findings also suggest that NPY may increase eating by acting on mechanisms of
      both meal initiation and of meal termination.

PMID- 9519274
TI  - The effects of extracellular pH and calcium manipulation on protein synthesis and
      response to anoxia/aglycemia in the rat hippocampal slice.
AB  - Extracellular pH modulates the function of the N-methyl-D-aspartate (NMDA)
      receptor, which may influence pathophysiological responses to glutamate. While
      damage due to oxygen and glucose deprivation or glutamate exposure is attenuated
      by acidification of the incubating medium of cultured neurons, neuron damage is
      enhanced in vivo following ischemia in hyperglycemic animals. A persistent
      inhibition of protein synthesis (to less than 5% of normoxic levels) is a
      reliable index of damage to neurons both in vivo and in the rat hippocampal
      slice. We explored the influence of extracellular pH and calcium manipulation on
      protein synthesis inhibition and energy failure due to anoxia/aglycemia or
      exposure to N-methyl-D-aspartate in the rat hippocampal slice. Moderate
      acidification of the medium during anoxia/aglycemia did not reduce the damage to
      protein synthesis in hippocampal neurons (9% of normoxic levels) and did not
      alter basal ATP levels or the rate of ATP depletion during anoxia/aglycemia.
      However, when calcium levels were lowered during the acidification and following
      the anoxia/aglycemia, protein synthesis was almost completely protected (84% of
      normoxic levels). Calcium reduction itself also attenuated the protein synthesis
      inhibition due to anoxia/aglycemia (to 55.6% of normoxic controls), but the
      protection was not as complete. In contrast, moderate acidification of the medium
      significantly reduced the damage to protein synthesis due to a brief exposure to
      NMDA (37% of control with NMDA, 78.9% of control with acidification during NMDA),
      even in the presence of extracellular calcium. Alkalinization of the medium
      exacerbated the protein synthesis inhibition following anoxia/aglycemia, and
      significantly reduced basal ATP levels (to 52% of normoxic control levels). Thus,
      pHo changes influence neuronal metabolism and response to anoxia/aglycemia. In
      addition, while acidification can reduce the excitotoxic damage caused by direct
      exposure to NMDA, it cannot reduce damage due to anoxia/aglycemia unless calcium
      is lowered concomitantly. Thus, both NMDA receptor activation and calcium are
      involved in the damage due to oxygen and glucose deprivation in the slice.

PMID- 9519275
TI  - Protein kinase C modulates ischemia-induced amino acids release in the striatum
      of hypertensive rats.
AB  - The role of protein kinase C (PKC) in mediating the ischemia-induced release of
      amino acids in the striatum was studied using an in vivo brain dialysis technique
      in the striatum of spontaneously hypertensive rats (SHRs). Using HPLC combined
      with fluorescence detection methods, we investigated the concentrations of amino
      acids in the dialysates produced by 20 min of transient forebrain ischemia. We
      studied the effects of an inhibitor of PKC, 1-(5-isoquinolinesulfonyl)-2
      methylpiperazine dihydrochloride (H7) and another isoquinoline analog (HA1004)
      with less inhibitory effect on the C kinase in ischemia-induced amino acids
      release. Bilateral carotid artery occlusion caused a marked reduction in the
      striatal blood flow by 91 +/- 6%. The extent of the cerebral blood flow (CBF)
      reduction were essentially the same among H7-, HA1004-, and the vehicle-treated
      groups. Forebrain ischemia produced a marked increase in glutamate (21-fold of
      the basal concentration), aspartate (19-fold) and taurine (16-fold). Pretreatment
      with H7 markedly attenuated the ischemia-in-duced release of these three amino
      acids to 3, 3 and 4-fold of the basal values, respectively. Increase of gamma
      aminobutyric acid (GABA) was also attenuated by H7 (vehicle; 2.46 +/- 1.26
      microM, H7; 0.62 +/- 0.75 mM). HA1004 did not affect the release of glutamate,
      aspartate or GABA during ischemia. The ischemia-induced release of taurine was
      significantly inhibited by HA1004 but the effect was much smaller than that of
      H7. These results thus indicate that PKC plays a major role in the ischemia
      induced release of amino acids in the striatum of SHR.

PMID- 9519276
TI  - Centrifugal fibers are the only GABAergic structures of the retina of the larval
      sea lamprey: an immunocytochemical study.
AB  - The structures of the retina immunoreactive to GABA are described in larval
      lamprey. Although GABAergic cells develop early in the retinas of vertebrates, no
      GABA-immunoreactive perikarya were observed in the retina of lamprey larvae. The
      only GABA-immunoreactive structures were beaded fibers of the centrifugal system,
      which produced a dense plexus at the level of the optic fiber/inner plexiform
      layer in both the central (photoreceptor-bearing) and lateral (no-photoreceptor)
      parts of the retina. These fibers do not ascend toward the outer plexiform layer.
      Nerve fibers in the optic nerve and neuronal perikarya of the M5 nucleus of the
      mesencephalon, which is known to project to the retina, were also GABA
      immunoreactive. The distribution of centrifugal fibers closely matches that of
      ganglion cells revealed by retrograde labelling with fluorescein-coupled dextran
      amine, and the presence of biplexiform ganglion cells in larvae is confirmed.
      That the ganglion cells and the centrifugal fibers appears to be the only
      structures differentiated in the lateral retina of the larva suggests that the
      GABAergic centrifugal fibers may have a role, perhaps the neurotrophic
      maintenance of retinal ganglion cells, during the very long larval phase of
      lampreys.

PMID- 9519277
TI  - N-methyl-D-aspartate receptors are indispensable for the formation of long-term
      potentiation in the rat suprachiasmatic nucleus in vitro.
AB  - Optic nerve (ON) stimulation caused a postsynaptic field potential in the
      suprachiasmatic nucleus (SCN) of rat hypothalamic slices. The postsynaptic field
      potential was suppressed by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), a non
      NMDA receptor antagonist, in a concentration-dependent manner, but not affected
      by D-amino-5-phosphonovaleric acid (APV), a competitive NMDA receptor antagonist.
      Tetanic stimulation to the ON induced long-term potentiation (LTP) in the SCN.
      Application of APV at 50 microM inhibited the induction of LTP by tetanic
      stimulation but CNQX at lower dose (5 microM) didn't inhibit it. These results
      suggest that NMDA receptors are indispensable for the induction of LTP after
      tetanic stimulation.

PMID- 9519278
TI  - 2,3-Dihydroxy-6-nitro-7-sulfamoyl-benzo(F)-quinoxaline (NBQX) increases
      fibroblast growth factor mRNA levels after contusive spinal cord injury.
AB  - We have previously demonstrated that the glutamatergic receptor (AMPA) antagonist
      2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)-quinoxaline (NBQX) reduces functional
      deficits in a standardized rat model of contusive spinal cord injury (SCI). NBQX
      not only acted to protect neurons from excitotoxicity but also, unexpectedly,
      enhanced sparing of white matter including axons of descending pathways. We have
      therefore investigated mechanisms through which NBQX could produce beneficial
      effects for white matter. We report here that NBQX elicits a rapid and selective
      induction of FGF2 mRNA levels in injured spinal cord. This novel effect could
      contribute to the therapeutic properties of NBQX in the treatment of SCI.

PMID- 9519279
TI  - Evidence for a role of N-methyl-D-aspartate receptors in L-arginine-induced
      attenuation of morphine antinociception.
AB  - Twice daily injections of L-arginine (50, 100 or 200 mg/kg, i.p.) for 4 days dose
      dependently, decreased morphine antinociception in male Swiss-Webster mice as
      measured by the tail-flick test. To determine the possible role of N-methyl-D
      aspartate (NMDA) receptor in the action of L-arginine, the effects of MK-801, a
      noncompetitive antagonist of the NMDA receptor and of LY 235959, a competitive
      antagonist of the NMDA receptor on L-arginine-induced attenuation of morphine
      antinociception were determined. MK-801 (0.01-0.10 mg/kg, i.p.) or LY 235959 (1.0
      4.0 mg/kg, i.p.) given 10 min before each injection of L-arginine (200 mg/kg,
      i.p.) reversed the action of the letter in a dose-dependent manner on morphine
      antinociception. It is concluded that NMDA receptors are involved in the action
      of L-arginine in attenuating morphine antinociception.

PMID- 9519280
TI  - Modulation of the acoustic startle reflex by infusion of corticotropin-releasing
      hormone into the nucleus reticularis pontis caudalis.
AB  - The amplitude of the acoustic startle reflex can be modulated by exposure to
      aversive stimuli or other conditions which evoke a state of fear. The
      neurotransmitters involved in this modulation are currently being investigated.
      Unilateral local infusion of corticotropin-releasing hormone (CRH; 0, 10, 20, 40
      and 80 ng) into the nucleus reticularis pontis caudalis (PnC), an obligatory
      synapse in the acoustic startle reflex, significantly elevated startle amplitude
      in a dose-dependent manner. The facilitation of startle began immediately
      following infusion, reached asymptote approximately 20-25 min later, and
      persisted throughout the remaining 60 min test session. This CRH-enhanced startle
      effect was blocked by infusion of the CRH antagonist, alpha-helical CRH9-41,
      immediately prior to CRH infusion. These results support an involvement of CRH at
      the level of the PnC in modulating the acoustic startle reflex.

PMID- 9519282
TI  - Behavioral sensitization to amphetamine is not accompanied by a decrease in the
      number of c-Fos containing cells in the striatum.
AB  - The expression of c-Fos-like immunoreactivity (FLI) and chronic Fos-related
      antigen-like immunoreactivity (FRALI) accompanying behavioral sensitization to
      amphetamine was assessed in male rat striatum. Animals were treated for four days
      with amphetamine (A; 5 mg/kg) or vehicle (V) and challenged with A or V on the
      fifth day. The number of FLI-positive cells in the striatum was enhanced in V-A
      and A-A groups as compared to control (V-V), while the number of FRALI-positive
      cells in the striatum was enhanced in the A-V and A-A groups as compared to
      control. These results suggest that the absence of a decrease in the number of
      striatal FLI-positive cells accompanying chronic amphetamine treatment is not due
      to antibody cross-reactivity with chronic FRAs, and that behavioral sensitization
      to amphetamine is not accompanied by a change in the number of striatal cells
      expressing c-Fos.

PMID- 9519281
TI  - Lesions of the nucleus basalis magnocellularis do not alter the proportions of
      pirenzepine- and gallamine-sensitive responses of somatosensory cortical neurones
      to acetylcholine in the rat.
AB  - The effects of S-alpha-amino-3-hydroxy-4-isoxozolepropionic acid (AMPA) lesions
      of the nucleus basalis magnocellularis on the M1/M2 nature of the responses of
      somatosensory cortical neurones to acetylcholine (ACh) in Sprague-Dawley rats
      were investigated by iontophoretic application and extracellular single unit
      recording. The responses were characterised using pirenzepine, an M1 receptor
      antagonist, and gallamine, an M2 antagonist. Eighty two neurones in control and
      94 neurones in lesioned animals were studied. In control animals, 37% of
      responses to ACh were sensitive to pirenzepine, gallamine or to both antagonists.
      This increased to 62% in lesioned animals, the proportions of pirenzepine- and
      gallamine-sensitive responses remaining unchanged. These results provide the
      first electrophysiological confirmation that both pirenzepine- and gallamine
      sensitive (M1 and M2) receptors occur postsynaptic to afferent cholinergic
      terminals and that their postsynaptic stimulation may produce both inhibition and
      excitation.

PMID- 9519283
TI  - Age-related decrease in centrally-mediated pressor response to clonidine in
      conscious rats.
AB  - An age-related change in pressor response to intracerebroventricular (i.c.v.)
      injection of clonidine in conscious rats was investigated. In 15-week-old rats,
      clonidine (2 to 20 micrograms) caused a dose-dependent pressor response
      concomitant with decrease in heart rate. The depressor response to i.c.v.
      clonidine at lower doses (2 and 5 micrograms) but not higher doses (10 and 20
      micrograms) was observed. The pressor response to clonidine in 20- and 30-week
      old rats was markedly diminished, and the depressor response appeared at any of
      the doses injected. However, no age-related change in heart rate responses was
      observed. These results suggest that the centrally mediated pressor response to
      clonidine is age-related and masks the depressor response.

PMID- 9519285
TI  - An electrophysiological investigation into the monosynaptic H-reflex in the rat.
AB  - In order to set up a non-invasive, reliable and reproducible model for
      investigating alpha-motoneuronal activity, we studied the electrophysiological
      features of a monosynaptic H-reflex in anaesthetised intact rats, anaesthetised
      and non-anaesthetised rats transected at the level of the obex. Electrical
      stimulation of the tibial nerve at the ankle elicited an H-reflex, an F-wave and
      a direct motor (M) response in the plantaris muscles of all preparations. The H
      reflex and F-wave exhibited very similar latencies. The H-reflex had a low
      threshold and a constant latency. Its amplitude increased as a function of
      stimulus intensity to reach a maximum value but then decreased when the stimulus
      intensity was further increased. It could follow high rates of stimulation
      without any change in shape or latency. The F-wave had a lower amplitude which
      together with its latency varied from one stimulus to the next. It appeared with
      intensities of stimulation that elicited an almost maximal M-response and did not
      decrease when the stimulation was increased. It did not appear systematically
      from one stimulus to the next. The H-reflex, but neither the F-wave nor the
      direct motor M-response, was depressed both by vibratory stimuli applied on the
      Achilles' tendon and following nociceptive stimulation of the flexor reflex
      afferents. This model could be used for assessing any potential direct effect on
      motoneurones of a physiological or pharmacological conditioning procedure.

PMID- 9519284
TI  - Phenidone blocks the increases of proenkephalin and prodynorphin gene expression
      induced by kainic acid in rat hippocampus: involvement of Fos-related antigene
      protein.
AB  - To determine the possible role of cyclooxygenase/lipoxygenase pathway in the
      regulation of proenkephalin (proENK) and prodynorphin (proDYN) gene expression
      induced by kainic acid (KA) in rat hippocampus, the effects of esculetin,
      aspirin, or phenidone on the seizure activity, proENK and proDYN mRNA levels, and
      the level of fos-related antigene (Fra) protein induced by KA in rat hippocampus
      were studied. Esculetin (5 mg/kg), aspirin (15 mg/kg), or phenidone (50 mg/kg)
      was administered orally five times every 12 h before the injection of KA (10
      mg/kg, i.p.). Seizure activity induced by KA was significantly attenuated by
      phenidone. However, neither esculetin nor aspirin affected KA-induced seizure
      activity. The proENK and proDYN mRNA levels were markedly increased 4 and 24 h
      after KA administration. The elevations of both proENK and proDYN mRNA levels
      induced by KA were inhibited by pre-administration with phenidone, but not with
      esculetin and aspirin. ProENK-like protein level increased by KA administration
      was also inhibited by pre-administration with phenidone, but not with esculetin
      and aspirin. The increases of proENK and proDYN mRNA levels induced by KA were
      well correlated with the increases of Fra protein level. Additionally, the
      induction of Fra protein was inhibited by pre-administration with phenidone, but
      not with esculetin and aspirin. The results suggest that blockade of both
      cyclooxygenase and lipoxygenase pathways appears to be responsible for increases
      of proENK and proDYN mRNA levels induced by KA via inhibiting the induction of
      Fra protein in rat hippocampus.

PMID- 9519286
TI  - Hypothermia attenuates the activation of protein kinase C in focal ischemic rat
      brain: dual autoradiographic study of [3H]phorbol 12,13-dibutyrate and
      iodo[14C]antipyrine.
AB  - Using phorbol 12,13-dibutyrate (PDBu) autoradiography, we investigated the effect
      of hypothermia or protein kinase C (PKC) activation in rat brain 2 h after focal
      ischemia. In normothermia, a significant increase of PDBu binding was observed in
      ischemic brain. Hypothermia suppressed the increase of PDBu binding in degree and
      extent. These observations suggest that intraischemic hypothermia attenuates the
      activation of PKC, and this may in part be participate in the protective effect
      of hypothermia.

PMID- 9519287
TI  - The effects of telencephalic lesions on visually mediated prey orienting behavior
      in the leopard frog (Rana pipiens). I. The effects of complete removal of one
      telencephalic lobe, with a comparison to the effects of unilateral tectal lobe
      lesions.
AB  - In this paper, we report studies aimed at characterizing the relationship between
      forebrain and midbrain systems involved in the control of prey orienting behavior
      in the leopard frog. In frogs, unilateral forebrain lesions, like unilateral
      tectal lobe lesions, have their most prominent effects in the contralateral
      monocular visual field. Such lesions produce partial reductions in response
      frequency in the binocular visual field as well. Similar sequelae follow
      unilateral tectal lobe removal. These findings suggest that the effects of
      unilateral forebrain removal can be largely attributed to removal of a
      facilitating influence on the tectal lobe on the same side of the brain. In the
      case of both forebrain and midbrain lesions, behavior was assayed not only in
      terms of the frequency with which animals responded to stimuli at various
      locations in the visual field (as is usually done) but also in terms of the
      latency of whatever responses were observed. A striking inverse relationship
      between response frequency and response latency was found, both in lesioned and
      in normal frogs. This relationship has not previously been noticed, doesn't
      appear to be an obvious consequence of any existing models of the neuronal
      circuitry underlying anuran orienting behavior, and is difficult to account for
      in terms of the time scales associated with axonal conduction times and synaptic
      delays. It may be easier to account for in terms of the responses to perturbation
      of large interacting systems of neurons, and this possibility seems worthy of
      further exploration.

PMID- 9519288
TI  - The effects of telencephalic lesions on visually mediated prey orienting behavior
      in the leopard frog (Rana pipiens). II. The effects of limited lesions to the
      telencephalon.
AB  - Unilateral removal of the telencephalon in the leopard frog, Rana pipiens,
      produces a contralateral deficit in visual prey orienting behavior [Patton and
      Grobstein, 1997]. In mammals, such deficits are most commonly associated with
      damage to the isocortex, a pallial derived structure. In contrast, we here report
      that in leopard frogs, lesions that remove substantial areas of one telencephalic
      lobe, including virtually the entire pallium, have no discernible effect on
      visual orienting behavior. Restricted lesions to the ventrocaudal telencephalon,
      however, produce an effect that closely resembles that produced by the complete
      removal of one telencephalic lobe. The 'critical area' that is both included in
      all lesions that are effective in producing a severe deficit and excluded from
      all ineffective lesions includes a portion of the caudal striatum. The striatum
      is known to play a significant role in anuran vision. It thus seems likely that
      the deficit produced by unilateral removal of the telencephalon in the leopard
      frog is due specifically to the removal of the caudal striatum. Unilateral
      lesions to the striatum have previously been shown to produce a contralateral
      deficit in visual orienting behavior in cats, and a role for the striatonigral
      pathway in the production of the visual orienting deficit that follows visual
      cortex lesions has been proposed. The current findings call attention to the
      possible general importance of the striatum in the control of vertebrate visual
      orienting behaviors.

PMID- 9519289
TI  - Protein-nucleic acid interactions folding and binding. Web alert.

PMID- 9519290
TI  - Protein-nucleic acid interactions.

PMID- 9519291
TI  - Helicases: a unifying structural theme?
AB  - The recent structure determinations of PcrA DNA helicase, NS3 RNA helicase, and
      Rep DNA helicase have revealed similarities between their folds. When these data
      are examined with sequence and biochemical analyses, as well as microscopy
      studies of hexameric helicases, a picture of a unifying structure and mechanism
      for all helicases is beginning to emerge.

PMID- 9519292
TI  - Novel site-specific DNA endonucleases.
AB  - Site-specific hydrolysis of DNA is common to many biological processes. Three new
      structures, FokI, I-CreI and PI-SceI, were reported in the past year, providing
      the first view of type IIs endonucleases and homing endonucleases. Together, they
      reveal an extraordinary set of new mechanisms by which endonucleases target the
      hydrolysis of specific DNA sequences.

PMID- 9519293
TI  - Type II DNA topoisomerases.
AB  - Type II DNA topoisomerases are enzymes capable of passing one DNA duplex through
      another. A combination of structural and biochemical analyses is illuminating the
      mechanistic details of this transport reaction, revealing the sites of DNA and
      nucleotide binding and the existence of large-scale domain motions.

PMID- 9519294
TI  - DNA binding within the nucleosome core.
AB  - The high resolution structure of the nucleosome core particle of chromatin
      reveals the form of DNA that is predominant in living cells and offers a wealth
      of information on DNA binding and bending by the histone octamer. Recent studies
      imply that chromatin is highly dynamic. This propensity for unfolding and
      refolding stems from the structural design of the nucleosome core. The histone
      fold motif, central to nucleosome structure, is also found in other proteins
      involved in transcriptional regulation.

PMID- 9519295
TI  - Eukaryotic transcription factors.
AB  - The structural characterization of eukaryotic transcription factors that interact
      with DNA has advanced on two fronts in the past two years. New complexes of
      transcription factors bound to TATA-box DNA include the TFIIA-TBP-DNA complex as
      well as human and archaeal TBP-DNA and TFIIB-TBP-DNA complexes, respectively. In
      addition, recent studies of proximal/distal promoter complexes demonstrate that
      DNA-binding motifs may be modified in nature by adding secondary structure
      elements to diversify DNA-binding specificities and affinities.

PMID- 9519296
TI  - Origin DNA-binding proteins.
AB  - The first step in DNA replication involves the recognition of origin DNA
      sequences by origin-binding proteins. The three-dimensional structures of three
      different origin DNA-binding proteins have recently been solved. These proteins
      form a structural class distinct from other DNA-binding proteins. One of the
      origin-binding proteins, Epstein-Barr virus nuclear antigen 1, most likely has
      two modes of DNA binding; the sequential use of these modes may be important for
      the initiation of DNA replication.

PMID- 9519297
TI  - Structural and functional insights provided by crystal structures of DNA
      polymerases and their substrate complexes.
AB  - New levels in the understanding of DNA replication have been achieved from recent
      crystal structure determinations of several DNA polymerases and their substrate
      complexes. The structure of an alpha family DNA polymerase from bacteriophage
      RB69 shows some similarities, but also considerable differences in structure and
      organization from the pol I family DNA polymerases. Also, the functions of three
      polymerase domains and their conserved residues have been clarified by studying
      structures of pol I family DNA polymerases complexed to their substrates. These
      structures also confirm that an identical two-metal ion catalytic mechanism
      proposed previously is used by both the nonhomologous pol I and pol beta family
      DNA polymerases.

PMID- 9519298
TI  - Pathways for protein folding: is a new view needed?
AB  - Theoretical studies using simplified models of proteins have shed light on the
      general heteropolymeric aspects of the folding problem. Recent work has
      emphasized the statistical aspects of folding pathways. In particular, progress
      has been made in characterizing the ensemble of transition state conformations
      and elucidating the role of intermediates. These advances suggest a
      reconciliation between the new ensemble approaches and the classical view of a
      folding pathway.

PMID- 9519299
TI  - Simplified proteins: minimalist solutions to the 'protein folding problem'.
AB  - Recent research has suggested that stable, native proteins may be encoded by
      simple sequences of fewer than the full set of 20 proteogenic amino acids.
      Studies of the ability of simple amino acid sequences to encode stable,
      topologically complex, native conformations and to fold to these conformations in
      a biologically relevant time frame have provided insights into the sequence
      determinants of protein structure and folding kinetics. They may also have
      important implications for protein design and for theories of the origins of
      protein synthesis itself.

PMID- 9519300
TI  - Kinetic studies of beta-sheet protein folding.
AB  - New studies have shown that folding of beta-sheet proteins can occur with and
      without intermediates, with fast to slow refolding rates and late to very late
      transition states. These experiments demonstrate that, despite early speculation
      to the contrary, beta-sheet protein folding does not appear to be fundamentally
      different from that of helical and mixed alpha, beta proteins.

PMID- 9519301
TI  - Structural aspects of GroEL function.
AB  - The chaperonin GroEL and its cofactor GroES facilitate protein folding in an ATP
      regulated manner. The recently solved crystal structure of the GroEL.GroES.(ADP)7
      complex shows that the lining of the cavity in the polypeptide acceptor state is
      hydrophobic, whereas in the protein-release state it becomes hydrophilic. Other
      highlights of the past year include the visualization of the allosteric states of
      GroEL with respect to ATP using cryo-electron microscopy, and an X-ray
      crystallographic analysis of the interaction between the apical domain of GroEL
      and a peptide.

PMID- 9519302
TI  - The alternative conformations of amyloidogenic proteins and their multi-step
      assembly pathways.
AB  - The conformational change hypothesis postulates that tertiary structural changes
      under partially denaturing conditions convert one of 17 normally soluble and
      functional human proteins into an alternative conformation that subsequently
      undergoes self-assembly into an amyloid fibril, the putative causative agent in
      amyloid disease. This hypothesis is consistent with Anfinsen's view that the
      tertiary structure of a protein is determined both by its sequence and the
      aqueous environment; the latter does not always favor the normally folded state.
      Unlike sickle cell hemoglobin assembly, where owing to a surface mutation,
      hemoglobin polymerizes in its normally folded conformation, amyloid proteins self
      assemble as a result of the formation of an alternative tertiary structure-a
      conformational intermediate formed under partially denaturing conditions. The
      pathway by which an amyloidogenic protein assembles into amyloid fibrils appears
      to involve quaternary structural intermediates that assemble into increasingly
      complex quaternary structures, including amyloid protofilaments, which ultimately
      assemble into amyloid fibrils. Several recent studies have discussed the multi
      step assembly pathway(s) characterizing amyloid fibril formation.

PMID- 9519303
TI  - Formation and stability of beta-hairpin structures in polypeptides.
AB  - Experimental work on peptide models with beta-hairpin structures has provided new
      insights into the formation and stability of this secondary structure element.
      Both the turn region and the antiparallel strand residues not only affect the
      overall stability of the hairpin, but also determine the type of hairpin formed.
      These results agree reasonably well with those from experimental and statistical
      analyses of beta-sheet structures in proteins.

PMID- 9519304
TI  - Hydrogen exchange and protein folding.
AB  - Amide hydrogen-deuterium exchange is a sensitive probe of the structure,
      stability and dynamics of proteins. The significant increase in the number of
      small, model proteins that have been studied has allowed a better understanding
      of the structural fluctuations that lead to hydrogen exchange. Recent technical
      advances enable the methodology to be applied to the study of protein-protein
      interactions in much larger, more complex systems.

PMID- 9519305
TI  - Measuring protein-protein interactions.
AB  - The binding of one protein to another provokes a variety of biophysical changes
      that can then be used as a measure of the binding reaction. Optical spectroscopy,
      particularly fluorescence, is the most flexible technique, but surface plasmon
      resonance biosensors, microcalorimetry and mass spectroscopy have recently shown
      significant development.

PMID- 9519307
TI  - Cachexia in heart failure is bad for you.

PMID- 9519306
TI  - A new evidence base for implantable defibrillator therapy.

PMID- 9519308
TI  - Epistenocardiac pericarditis: atrial fibrillation is due to the infarct, not
      pericarditis.

PMID- 9519309
TI  - Intravascular ultrasound-guided PTCA.

PMID- 9519310
TI  - Percutaneous recanalization of complete artery occlusions.

PMID- 9519311
TI  - The challenge of managing unstable angina.

PMID- 9519312
TI  - Cardiomyoplasty in severe heart failure: where do we stand?

PMID- 9519313
TI  - Growth hormone, lipoprotein(a) and cardiovascular disease.

PMID- 9519314
TI  - Clinical application and image interpretation in intracoronary ultrasound. Study
      Group on Intracoronary Imaging of the Working Group of Coronary Circulation and
      of the Subgroup on Intravascular Ultrasound of the Working Group of
      Echocardiography of the European Society of Cardiology.

PMID- 9519316
TI  - Family history as a risk factor of coronary heart disease in patients under 60
      years of age.
AB  - The role of family history as a risk factor of coronary heart disease was
      explored in the first-degree relatives of 121 female and 586 male survivors of a
      recent acute myocardial infarction and in those of 130 control women. It was
      significantly more common for female patients than male patients to have first
      degree relatives with coronary artery disease before the age of 65 (76% vs 62%, P
      = 0.0026). For the sisters of the female patients the cumulative risk of coronary
      heart disease by the age of 65 years was almost twice that of the sisters of the
      male patients (25.9% vs 15.8%, P = 0.0123). The risk for the brothers of the
      females did not significantly differ from that of the brothers of the male
      patients, but it was 3.5 times that of the brothers of the controls. Thus, while
      a history of coronary heart disease in first-degree relatives is a risk factor
      for the disease, the risk is greater in women than in men.

PMID- 9519315
TI  - Improvement of myocardial ischaemia by lipid lowering drugs.

PMID- 9519317
TI  - Long-term prognosis in unstable angina. The importance of early risk
      stratification using continuous ST segment monitoring.
AB  - AIMS: To assess the ability of clinical characteristics, admission ECG and
      continuous ST segment monitoring in determining long-term prognosis in unstable
      angina. METHODS: Two hundred and twelve patients with unstable angina (mean age
      59 years), presenting within 24 h of an acute episode of angina were recruited at
      three hospitals and treated with standardized medical therapy. All patients kept
      chest pain charts and underwent ST segment monitoring for 48 h. The occurrence of
      death, myocardial infarction, and need for revascularization was assessed over a
      median follow-up of 2.6 years. RESULTS: The risk of death of myocardial
      infarction was greatest in the first 6-8 weeks after admission. Admission ECG ST
      depression and the presence of transient ischaemia predicted increased risk of
      subsequent death or myocardial infarction, whereas a normal ECG predicted a good
      prognosis. In 14 patients, ST segment monitoring provided the only evidence of
      recurrent ischaemia, and 72% of this group suffered an adverse event. Transient
      ischaemia and a history of hypertension were the most powerful independent
      predictors of death or myocardial infarction. CONCLUSIONS: Adverse events in
      unstable angina occur early after admission and can be predicted by clinical and
      ECG characteristics, and by the presence of transient ischaemia during ST segment
      monitoring. Risk stratification by these simple assessments can identify patients
      with unstable angina at high risk.

PMID- 9519318
TI  - Low dose imipramine improves chest pain but not quality of life in patients with
      angina and normal coronary angiograms.
AB  - AIMS: We investigated patients with chest pain and normal coronary angiograms to
      determine whether low dose imipramine prescribed as add-on therapy to
      conventional anti-anginals reduced the incidence of chest pain and whether this
      led to an overall improvement in quality of life. METHODS AND RESULTS: We
      performed a randomized, double-blind, cross-over trial of imipramine 50 mg daily
      vs placebo in 18 women (median age 53 years; range 35-72) with chest pain and
      normal coronary angiograms who were suffering at least two anginal episodes per
      week despite conventional anti-anginal medication. Each treatment phase lasted 5
      weeks and the incidences of chest pain and side effects were carefully recorded.
      Quality of life was monitored using a validated health profile questionnaire
      scoring perceived distress in six domains (pain, energy, mobility, sleep,
      emotional reactions and social isolation). The total number of chest pain
      episodes was significantly less during active treatment compared to placebo [11
      (3-22) vs 21 (16-28)--median (interquartile range); P = 0.01]. However, a high
      incidence (83%) of side effects was reported during active treatment and three
      patients had to be withdrawn from the study as a consequence. No significant
      improvement was detected in any of the six quality of life domains when
      imipramine was compared to placebo. CONCLUSION: Imipramine reduces the incidence
      of chest pain in patients with chest pain and normal coronaries who remain
      symptomatic despite conventional anti-anginal therapy. The failure to demonstrate
      associated improvements in quality of life may have been due to the high
      incidence of side effects.

PMID- 9519319
TI  - The persistence of hibernating myocardium after acute myocardial infarction.
AB  - OBJECTIVE: To establish the persistence of hibernating myocardium initially
      detected after myocardial infarction treated with thrombolysis. METHODS AND
      RESULTS: Fourteen patients underwent gated positron emission tomography with 18
      fluoro-deoxyglucose and N13-ammonia at a median of 8 days after first myocardial
      infarction. Repeat scans were performed at a median of 13 weeks post-infarction.
      A total of 148 (30.9%) myocardial segments showed reduced N13-ammonia uptake at
      the time of the first scan compared with 154.5 (32.2%) segments at the time of
      repeat imaging. The median change in the number of segments with reduced
      perfusion was -1.0. Initially 13 subjects had hibernating myocardium, seven
      patients had large areas and six had smaller regions. Six (46.2%) subjects had
      repeat scans showing unchanged areas of hibernating tissue and seven had second
      scans demonstrating changes in the size of the region of hibernating myocardium.
      One patient had no hibernating myocardium on either scan. CONCLUSIONS: Positron
      emission tomography performed several months after myocardial infarction
      demonstrates significant changes in myocardial perfusion. However, a reduction in
      the number of segments with reduced perfusion does not always result in an
      improvement in myocardial metabolism and contraction. Whilst most regions of
      hibernating myocardium were still present several months after infarction, in
      only approximately half was the size of the mismatched region unchanged.
      Therefore it is not possible to predict the fate of hibernating myocardium which
      is present after infarction.

PMID- 9519321
TI  - Improvement in left ventricular ejection fraction and wall motion after
      successful recanalization of chronic coronary occlusions.
AB  - AIMS: This study assessed changes in left ventricular ejection fraction and
      regional radial shortening after successful angioplasty of chronic coronary
      occlusions. METHODS: We studied 95 patients with angina pectoris or exercise
      induced ischaemia with a successfully recanalized chronic (median duration 4.3
      months) coronary occlusion. Intracoronary stents were implanted in 71%. Left
      ventriculograms were obtained at baseline and after 6.7 +/- 1.4 months. Left
      ventricular ejection fraction and regional radial shortening were determined by a
      computer-assisted method. RESULTS: Left ventricular ejection fraction increased
      from 0.62 +/- 0.13 at baseline to 0.67 +/- 0.11 at follow-up (P < 0.001). The
      change in left ventricular ejection fraction in patients with a patent artery and
      in patients with reocclusion (n = 8) was 0.05 +/- 0.06 and 0.01 +/- 0.04,
      respectively (P = 0.04). Regional radial shortening in the territory of the
      recanalized artery increased by 16% (from 0.28 +/- 0.11 to 0.32 +/- 0.11, P <
      0.001) in patients with a patent artery at follow-up, but was unchanged in
      patients with reocclusion. CONCLUSION: Long-term patency after recanalization of
      old, chronic coronary occlusions in patients with angina pectoris is associated
      with improvement in global and regional left ventricular function. This may be a
      result of recovery of hibernating myocardium and supports the strategy of
      recanalizing chronic coronary occlusions.

PMID- 9519320
TI  - Acute and one year follow-up results after vessel size adapted PTCA using
      intracoronary ultrasound.
AB  - AIMS: Recent randomized clinical trials have reported a reduction in restenosis
      with intracoronary stents and have suggested that this restenosis reduction is a
      result of the higher immediate luminal gain, in comparison to conventional
      percutaneous transluminal coronary angioplasty (PTCA). The hypothesis of this
      study is based on the assumption that PTCA results may be optimized by
      determining vessel dimensions before intervention, using intravascular
      ultrasound. This may lead to long-term PTCA results equivalent to PTCA and the
      additional placement of a stent. The purpose of this prospective non-randomized
      single-centre study was to evaluate (1) the safety and efficacy and (2) the long
      term outcome of vessel-size adapted PTCA in patients with native coronary artery
      obstructions. METHODS AND RESULTS: From January 1995 to December 1995 the
      morphological dimensions of target lesions were determined in 144 patients with
      152 lesions by intravascular ultrasound prior to conventional balloon
      angioplasty. Quantitative assessment of the vascular dimensions were assessed on
      line and the diameter of the balloon catheter was adapted to the external elastic
      membrane diameter at the lesion site. Using this strategy, mean balloon diameter
      was 4.0 +/- 0.5 mm and mean pressure for complete balloon expansion was 7 +/- 2
      atmospheres. Acute and one year follow-up results were obtained in all 144
      patients. Acute events occurred in two patients (one death and one acute surgical
      revascularization). During one year follow-up, 16 patients (12%) had a clinical
      event including one cardiac death, two transmural myocardial infarctions, 10
      repeat PTCAs within the target lesion and three elective coronary artery bypass
      grafts (CABG). In 75% (n:112) control angiography was performed and revealed an
      angiographic restenosis rate of 21% using the NHLBI criteria of a diameter
      stenosis > 50%. CONCLUSION: Intravascular ultrasound provides an accurate and
      precise description of vascular dimensions at the site of the stenotic lesion.
      The use of balloon diameters following these measurements appears to be (1) safe
      in the acute setting with a low number of in hospital events and (2) gives a low
      restenosis rate and number of clinical events at one year follow-up. These
      promising results warrant verification in larger-scale randomized trials.

PMID- 9519322
TI  - Influence of pacing modalities on the incidence of atrial fibrillation in
      patients without prior atrial fibrillation. A prospective study.
AB  - AIM: Many studies suggest that patients who receive a physiological pacemaker
      have a reduced incidence of atrial fibrillation compared to patients receiving a
      ventricular pacemaker. METHODS: In order to evaluate the impact of different
      pacing modalities on the incidence of atrial fibrillation, we prospectively
      analysed 210 patients. Patients with previous episodes of atrial fibrillation
      were excluded from the study. The patient population included 110 patients paced
      for sick sinus syndrome and 100 patients paced for total atrioventricular block
      or second degree type atrioventricular block. RESULTS: Patients were followed for
      5 years; the incidence of atrial fibrillation was 10% at 1 year, 23% at 3 years
      and 31% at 5 years. There was an increase in the incidence of atrial fibrillation
      in patients receiving a ventricular pacemaker compared to patients receiving a
      physiological pacemaker. CONCLUSION: The pacing modality appeared to influence
      the incidence of atrial fibrillation in paced patients; patients with ventricular
      pacing had a significantly higher incidence of arrhythmias than did patients with
      physiological pacing.

PMID- 9519323
TI  - The role of infarction-associated pericarditis on the occurrence of atrial
      fibrillation.
AB  - AIMS: Transient atrial fibrillation is a relatively common arrhythmia in the
      early phase of acute Q-wave myocardial infarction. However, the role of
      infarction-associated pericarditis on the genesis of atrial fibrillation is
      controversial. This study was designed to examine the relative importance of
      infarction-associated pericarditis among other clinical variables on the genesis
      of transient atrial fibrillation in patients with acute myocardial infarction.
      METHODS AND RESULTS: Three hundred and ninety-eight patients with acute Q-wave
      myocardial infarction were examined carefully by means of auscultation, ECG, two
      dimensional echocardiography and haemodynamic measurements. The diagnosis of
      pericarditis was made on the basis of pericardial rub detected during the first 3
      days after admission. At least 0.5 mm of PQ-segment depression from a TP segment
      lasting more than 24 h in both limb and precordial leads was considered
      diagnostic of PQ-segment depression. Atrial fibrillation was present in 76
      patients (19%). Sixteen (42%) of 38 patients with PQ-segment depression had
      atrial fibrillation, whereas 23 (30%) of 77 patients with pericardial rub had
      atrial fibrillation. Based on ten clinical variables, multivariate analysis was
      performed to determine the important variables related to the occurrence of
      atrial fibrillation. PQ-segment depression (chi-square = 4.10, P < 0.05) was
      selected with age (chi-square = 10.52, P < 0.005), the number of left ventricular
      segments with advanced asynergy (chi-square = 7.73, P < 0.01) and pericardial
      effusion (chi-square = 7.95, P < 0.005) as important factors related to atrial
      fibrillation. Patients with PQ-segment depression had a significantly higher
      pulmonary capillary wedge pressure than those without it. CONCLUSION: Among
      patients with infarction-associated pericarditis, those with PQ-segment
      depression represent atrial involvement associated with extensive myocardial
      damage and hence, PQ-segment depression is one of the clinical signs related to
      the occurrence of atrial fibrillation in acute Q-wave myocardial infarction.

PMID- 9519324
TI  - Right atrial free wall conduction velocity and degree of anisotropy in patients
      with stable sinus rhythm studied during open heart surgery.
AB  - AIMS: Although the perpetuation of several supraventricular arrhythmias is
      critically dependent upon intra-atrial conduction, the literature lacks detailed
      information on normal values of conduction velocity and degree of anisotropy. In
      order to explore these factors further, we have measured conduction velocities at
      the right atrial free wall during sinus rhythm and during atrial pacing in four
      directions parallel and perpendicular to the atrioventricular groove in patients
      with normal atria and stable sinus rhythm. METHODS AND RESULTS: Using a Bard
      Cardiac Mapping System, atrial ECGs were recorded using a 3 x 4 cm electrode
      array with 56 equally spaced bipolar electrodes in 12 patients undergoing open
      heart surgery due to ischaemic heart disease or Wolf-Parkinson-White syndrome. A
      bipolar pen probe connected to a Medtronic 5328 stimulator was used for pacing at
      a 10% higher rate than sinus rhythm. The local activation times were manually set
      and isochronal activation maps were created for each recording. The conduction
      velocities were calculated from the activation maps over a distance ranging from
      2.2 to 4.2 cm. The majority of the activation maps showed no signs of anisotropy;
      the others had less than 15% spatial inhomogeneity of conduction. Mean conduction
      velocity, calculated from five consecutive beats, was 88 +/- 9 cm.s-1 (mean +/-
      SD), ranging between 68 +/- 4 and 103 +/- 3 cm.s-1 during sinus rhythm. Mean
      conduction velocity during atrial pacing was 81 +/- 16 cm.s-1 at a propagation
      direction of 0 degree, 74 +/- 14 cm.s-1 at a 90 degrees direction, 79 +/- 12 cm.s
      1 at 180 degrees and 78 +/- 20 cm.s-1 at 270 degrees, where 0 degree was parallel
      to the atrioventricular groove in the cranial direction and the angle increased
      counter-clockwise. Mean conduction velocity during sinus rhythm was significantly
      higher (P < 0.05) than during atrial pacing at the 90 degrees and 180 degrees
      directions but not compared to atrial pacing at 0 degree or 270 degrees. There
      was no significant difference in mean conduction velocity in different directions
      during atrial pacing. CONCLUSION: Although anisotropy was documented during
      conduction velocity in individual cases, conduction velocity was not dependent on
      propagation direction at the epicardial right atrial free wall in patients with
      stable sinus rhythm. These findings do not exclude the presence of internodal
      preferential pathways as these are located sub-epicardially and a marked
      transmural discordance in activation has previously been documented in the
      vicinity of such pathways.

PMID- 9519326
TI  - Structural alterations in the latissimus dorsi muscles in three patients more
      than 2 years after a cardiomyoplasty procedure.
AB  - AIMS: The long-term effects of the use of the latissimus dorsi muscle for dynamic
      cardiomyoplasty were studied. Skeletal muscle fast fatiguable type II fibres are
      transformed to highly fatigue-resistant type I fibres in animal models, and is
      assumed to occur in men. However, it is not known whether this same
      transformation occurs in patients with chronic heart failure. METHODS AND
      RESULTS: Three patients who underwent a cardiomyoplasty procedure (pre-operative
      NYHA class IV) were studied. The left latissimus dorsi muscle was stimulated,
      according to routine clinical protocol, with 30 Hz bursts in a 2:1 ratio to
      cardiac activation. The patients died more than 2 years after surgery and five
      autopsy samples were obtained at defined places in the wrapped muscle. In the
      proximal part of the latissimus dorsi muscle, the type I fibres comprised 68-80%
      in all three patients, whereas peroperatively type I fibres comprised 17-30%
      indicating significant but not complete transformation. Transformation in the
      latissimus dorsi muscle as a whole appeared to be inhomogeneous, with type I
      fibres ranging from 10-80%. An extensive amount of muscle fibre appeared to be
      replaced by fatty tissue (10%-50%). This occurred at random and resulted in
      complete loss of muscle structure. A significant increase in the density of small
      arteries was observed in the latissimus dorsi after transformation. CONCLUSIONS:
      In these patients, muscle fibre type transformation was not as complete as that
      observed in animal experiments, and was accompanied by loss of muscle viability.
      The stimulation current in the latissimus dorsi muscle appeared not to be the
      direct cause of local tissue lipomatosis or collagen deposition.

PMID- 9519327
TI  - Donor ACE gene polymorphism: a genetic risk factor for accelerated coronary
      sclerosis following cardiac transplantation.
AB  - AIMS: To investigate the role of angiotensin converting enzyme (ACE) (I/D) gene
      polymorphism in the development of coronary sclerosis after cardiac
      transplantation. METHODS AND RESULTS: Eighty cardiac transplant recipients (44
      transplant associated coronary artery disease; 36 non-transplant associated
      coronary artery disease) and their donors were genotyped by polymerase chain
      reaction. The allele frequencies of the recipients in the transplant associated
      coronary artery disease and non-transplant associated coronary artery disease
      groups (I = 0.47 and 0.48, D = 0.53 and 0.52, respectively) did not differ
      significantly between the groups. However, there was a negative association
      between the frequency of the I allele in the donor and the development of
      transplant associated coronary artery disease. The D allele in the donor
      population of the non-transplant associated coronary artery disease group had a
      significantly (P < 0.01) lower frequency (0.35) than either the transplant
      associated coronary artery disease group (0.53) or that of the general population
      (0.57). Other factors analysed were recipient family history, cholesterol levels,
      age, sex and body mass index, donor age and acute rejection, of which the
      significant (P < 0.05) factors were acute rejection and sex of the recipient.
      CONCLUSION: These results suggest that the ACE genotype of the donor organ may be
      an additional risk factor for the development of coronary artery disease
      following cardiac transplantation and that tissue rather than circulating ACE
      could be implicated in the pathogenesis of this disease.

PMID- 9519325
TI  - A comparison of adult pulmonary autograft diameter measurements with
      echocardiography and magnetic resonance imaging.
AB  - In 38 consecutive patients the pulmonary autograft was used in aortic root
      replacement. Investigations were performed with transthoracic echocardiography,
      transoesophageal echocardiography and magnetic resonance imaging in 31, 27 and 27
      patients respectively. The mean age at operation was 28.7 years (range 19.0-52.0)
      and the follow-up period was 2.8 years (range 0.8-6.7). The pulmonary autograft
      diameter was measured at the subannular region (1), at the annulus at the hinge
      points of the valve leaflets (2), at the sinus (3), at the sino-tubular junction
      (4) and at the distal part of the autograft (5). With transoesophageal
      echocardiography the mean systolic measurements at levels 1 to 5 were 32, 31, 42,
      35 and 34 mm, respectively. The corresponding diastolic measurements were
      smaller: 25, 28, 42, 35 and 34 mm respectively. There was no significant
      difference between transthoracic echocardiography and transoesophageal
      echocardiography measurements of the proximal autograft (levels 1-3). Diameters
      obtained with magnetic resonance imaging were 1 to 3 mm larger than those
      obtained with transthoracic echocardiography and transoesophageal
      echocardiography (P < 0.05), except the annulus at systole (P > 0.3).
      CONCLUSIONS: The mean pulmonary autograft diameters measured using transthoracic
      echocardiography, transoesophageal echocardiography and magnetic resonance
      imaging were larger than native aortic and pulmonary diameters of a normal
      population in the same age group. Diameters of the distal 2 levels could not be
      imaged reliably with transthoracic echocardiography. Magnetic resonance imaging
      diameter measurements were, in general, larger than with echocardiography.

PMID- 9519328
TI  - Hyperinsulinaemia, regional adipose tissue distribution and left ventricular mass
      in normotensive, elderly, obese subjects.
AB  - Obesity is a metabolic condition, related to abnormalities of the glyco
      insulinaemic metabolism, and plays a substantial role in the development of
      cardiovascular disease. The aim of this study was to establish a correlation
      among left ventricular mass, evaluated echocardiographically according to Penn
      Convention criteria, blood pressure, evaluated by ambulatory blood pressure
      monitoring, anthropometric indices for evaluation of body mass index and waist to
      hip ratio circumference, regional adipose tissue distribution, evaluated by
      ultrasound measurements of visceral adipose tissue, and insulin resistance,
      evaluated by hyperinsulinaemia by oral glucose tolerance test. We selected two
      groups of elderly male subjects well matched for age (68.5 +/- 6.4 years): 29
      obese and 20 lean, with a body mass index, respectively, of 34.6 +/- 2.9 and 23.4
      +/- 2.3. Statistical analysis was carried out by Student's t-test and linear
      regression analysis. In spite of the fact that statistical analysis showed a
      higher, though not statistically significant, systolic and diastolic mean blood
      pressure in the lean subjects, we found an increased left ventricular mass in
      obese subjects (P < 0.0001). The area under the insulin curve was higher in obese
      than in lean subjects (P < 0.0001) while the area under the glucose curve was not
      significantly different in the two groups. Furthermore, linear regression
      analysis showed that in obese subjects left ventricular mass was strictly
      correlated with visceral adipose tissue (r = 0.607; P < 0.0001) and
      hyperinsulinaemia (r = 0.615; P < 0.0001). In conclusion, our data suggest that
      centripetal adipose tissue distribution and hyperinsulinaemia, independent of
      blood pressure values, are closely correlated with left ventricular mass.

PMID- 9519329
TI  - Echocardiography and fatty acid single photon emission tomography in predicting
      reversibility of regional left ventricular dysfunction after coronary
      angioplasty.
AB  - AIMS: The present study was performed to evaluate whether echocardiographic
      assessment of end-diastolic wall thickness and myocardial fatty acid metabolic
      single-photon emission tomographic imaging with 123I-beta-methyl-iodophenyl
      pentadecanoic acid could be used to predict the reversibility of dysfunctional
      left ventricular segments after coronary artery revascularization. METHODS AND
      RESULTS: Twenty-eight patients with wall motion abnormalities related to stenosed
      coronary arteries underwent resting two-dimensional echocardiography and 123I
      beta-methyl-iodophenyl pentadecanoic acid single photon emission tomography
      before coronary angioplasty. A dysfunctional segment was considered viable by the
      presence of either preserved wall thickness (> or = 75% of the thickness of a
      normal segment) or preserved fatty acid uptake (> or = 50% of that in normal
      region). Echocardiography was repeated after successful angioplasty. Functional
      recovery was observed in 32 (74%) of 43 hypokinetic and nine (100%) of nine
      akinetic segments with preserved wall thickness and in 11 (79%) of 14 thinned
      akinetic segments with preserved fatty acid uptake. In contrast, no functional
      recovery was observed in any of the 13 thinned segments with < 50% fatty acid
      uptake (eight akinetic and five dyskinetic). Using combined evaluation of both
      methods, positive and negative predictive values for post-revascularization
      functional outcome were 79% and 100%, respectively, in all dysfunctional
      segments; and 87% and 100%, respectively, in akinetic/dyskinetic segments.
      CONCLUSIONS: The present study showed that echocardiographic findings of
      preserved wall thickness and single-photon emission tomography evaluated
      preserved fatty acid uptake in thinned segments are reliable predictors of post
      revascularization functional recovery and the concordant absence of both
      accurately predict negative outcome.

PMID- 9519331
TI  - Contribution of heart rate variability to long-term risk stratification after
      myocardial infarction.

PMID- 9519330
TI  - The value of the coefficient of variation in assessing repeat variation in ECG
      measurements.
AB  - AIMS: The coefficient of variation is a popular measure for describing the amount
      of repeat variability present in ECG measurements from recording to recording.
      However, it can be misleading. The aim of the present study was to assess repeat
      variation (reclassification) in computer measured ECG criteria, i.e. positive to
      negative or vice versa, and compare this with the coefficient of variability.
      METHODS AND RESULTS: Two ECGs were obtained from each of 295 patients, one day
      apart, and separately from a further 364 patients, several minutes apart. All
      patients were considered to be in a stable condition. Estimates of the
      coefficients of variation were obtained for a number of ECG parameters used in
      the diagnosis of left ventricular hypertrophy. Corresponding reclassification
      rates of relevant ECG criteria were also calculated. Large coefficients of
      variation were observed in voltage parameters, e.g. R in V5 (20% for day-to-day
      recordings and 6% for minute-to-minute recordings) while the corresponding
      reclassification rates were 8% and 0% respectively. The repeat variation in the
      diagnosis of left ventricular hypertrophy was up to 5% for day-to-day recordings
      and up to 3% for minute-to-minute recordings based on several different criteria.
      CONCLUSION: A large coefficient of variation in a particular variable does not
      necessarily correspond to a high reclassification rate. A better measure of the
      impact of ECG variability for a particular measurement is obtained from its
      reclassification rate. In turn, this may have a minimal effect on the overall
      diagnosis of a particular abnormality.

PMID- 9519332
TI  - Pacing in hypertrophic cardiomyopathy.

PMID- 9519333
TI  - Mitral valve prolapse vs flail leaflets.

PMID- 9519334
TI  - Sex differences in short-term survival after initial myocardial infarction.

PMID- 9519335
TI  - The Greek Heart House--a new venture.

PMID- 9519336
TI  - The Munster Heart Study (PROCAM). Results of follow-up at 8 years.
AB  - The Munster Heart Study (PROCAM) was initiated in 1979 in order to examine
      cardiovascular risk factors, cardiovascular events including myocardial
      infarction and stroke, and mortality in people at work. Examination at entry
      comprised a standardized case history, measurement of blood pressure and
      anthropometric data, a resting electrocardiogram, and measurement of more than 20
      laboratory parameters in a fasting blood sample. The prevalence data in this
      report are based upon a single examination of 17,437 men aged 40.4 +/- 11.3 years
      (mean +/- SD) and 8065 women aged 35.7 +/- 12.1 years, which took place between
      1979 and 1991. Severe hypercholesterolaemia (> 300 mg.dl-1) was seen in 5% of men
      and 8% of women aged 45 to 64 years. In men, the prevalence of
      hypertriglyceridaemia (> 200 mg.dl-1) rose from 5% at age 20 to 20% at age 45 and
      remained constant thereafter; in women the prevalence of hypertriglyceridaemia
      increased linearly from 2% at age 20 to 7% at age 60. The LDL/HDL ratio was
      higher in men than in women at all age groups; in the age group 45 to 64 years,
      LDL/HDL ratios > 5 were approximately twice as common in men. Lipoprotein(a)
      levels were distributed in a highly skewed fashion. In men, a slight rise in the
      geometric mean lipoprotein(a) concentration occurred with age, whereas in women a
      dramatic increase was seen after age 40. Using multivariate analysis by the
      multiple logistic function method, total cholesterol, HDL cholesterol, LDL
      cholesterol and log-transformed triglycerides showed a significant (P < 0.001)
      age-adjusted correlation with the presence of major coronary events. A risk
      algorithm has been developed for men aged 40 to 65 years which takes into account
      the independent risk factors of HDL cholesterol, LDL cholesterol, triglycerides,
      fibrinogen, age, systolic blood pressure, cigarette smoking, presence of diabetes
      mellitus and family history of myocardial infarction and angina pectoris. This
      algorithm can be used in clinical practice to calculate the 8-year risk of an
      individual suffering a myocardial infarction.

PMID- 9519337
TI  - European and American recommendations for coronary heart disease prevention.
AB  - European and American recommendations for coronary heart disease prevention put
      patients with clinically manifest coronary heart disease, or other major
      atherosclerotic disease, as the top priority for prevention. Coronary patients
      should have professional support to stop smoking, eat a healthier diet (reduce
      the dietary intake of fat to 30% or less of total energy; saturated fat to no
      more than one third of total fat intake, cholesterol to less than 300 mg per day;
      increase monounsaturated and polyunsaturated fat from both vegetables and marine
      sources; increase fresh fruit and vegetables) achieve optimal weight, and become
      physically fitter through regular aerobic exercise. The intensity of lifestyle
      intervention and the level of professional support required to achieve change
      should be determined by the absolute risk of a further major ischaemic event,
      based on an assessment of all risk factors, and this should also influence the
      threshold for drug therapy in relation to blood pressure, lipoproteins and
      glucose, rather than just the individual levels of these risk factors. In
      addition to lifestyle changes (reducing weight and restricting salt and alcohol
      as appropriate) blood pressure in coronary patients should be lowered if
      necessary with drug therapy. For these patients blood pressure should be
      consistently less than 140/90 mmHg. Lifestyle changes will reduce total
      cholesterol (and in particular LDL cholesterol) increase HDL cholesterol and
      lower triglycerides. Drug therapy may also be required and in coronary patients
      total cholesterol should be kept consistently below 4.8 mmol.l-1, and this
      threshold may be further reduced with the publication of new trial results. In
      insulin-dependent diabetes, rigorous metabolic control reduces the risk of
      microvascular complications and therefore for coronary patients with insulin
      dependent or non-insulin dependent diabetes mellitus this is a desirable
      objective. As diabetics with coronary disease are at substantially higher risk of
      coronary morbidity and mortality compared with non-diabetics the threshold for
      treating blood pressure and lipids with drug therapy should be lower. In coronary
      patients, selected prophylactic drug therapy is indicated in the form of aspirin,
      beta-blockers, ACE inhibitors and systemic anticoagulants which, together with
      lipid lowering drug therapy, have all been shown to reduce coronary mortality and
      improve life expectancy. When a patient presents with coronary disease, and
      particularly when there is a family history of premature coronary heart disease,
      the opportunity of screening first degree relatives should be taken with a view
      to primary prevention.

PMID- 9519338
TI  - Lipoprotein metabolism.
AB  - Hyperlipidaemias are important risk factors for coronary heart disease. To
      prevent and treat the different forms of hyperlipidaemias it is important to
      understand lipoprotein metabolism. The current knowledge on lipoprotein
      metabolism is based on many different biochemical and metabolic studies which are
      summarized here for a clinically orientated overview. Exogenous fat is
      transported in chylomicrons from the intestine to the liver. After entry in the
      blood stream the chylomicrons are hydrolyzed by the endothelial-bound lipoprotein
      lipase. The chylomicron remnants are rapidly taken up into the liver via the LDL
      receptor and the LDL receptor-related protein. Apolipoprotein E and lipoprotein
      lipase are the recognition signals for these receptors. The liver utilizes the
      exogenous fat and can release surplus lipids via VLDL into the blood. The VLDL
      are another substrate for lipoprotein lipase. The remaining VLDL remnants can
      either be taken up into the liver or are hydrolyzed to LDL. LDL delivers
      cholesterol to all body cells via the LDL receptor. The level of LDL cholesterol
      is regulated by the amount of LDL receptor, and defects in the LDL receptor
      molecule lead to hypercholesterolaemia. The level of triglyceride-rich remnants
      is regulated by the amount and activity of lipoprotein lipase and defects in this
      enzyme cause mixed hyperlipidaemias. Both these forms of hyperlipoproteinaemias
      are the most frequent and represent major risk factors for arteriosclerosis.

PMID- 9519339
TI  - Atherogenic, dense low-density lipoproteins. Pathophysiology and new therapeutic
      approaches.
AB  - It is well established that elevated circulating concentrations of cholesterol
      rich, low-density lipoproteins (LDL) represent a major risk factor for the
      premature development of coronary artery disease. Only recently, however, has
      attention been drawn to the relationship between the qualitative features of
      plasma LDL particles and cardiovascular risk, particularly in view of the
      frequent occurrence of increased levels of dense, small LDL in coronary artery
      disease patients. Combined hyperlipidaemia, a frequent form of dyslipidaemia
      which is associated with premature atherosclerosis, is characterized by elevated
      plasma concentrations of both triglyceride-rich, very-low-density lipoproteins
      (VLDL) and LDL. In combined hyperlipidaemia patients, small, dense LDL (d 1.04
      1.06 g.ml-1) predominate over the light (d 1.02-1.03 g.ml-1) and intermediate (d
      1.03-1.04 g.ml-1) LDL subpopulations. Dense LDL are highly atherogenic as a
      result of their low binding affinity for the LDL receptor, their prolonged plasma
      half-life and low resistance to oxidative stress. Biological modification of
      dense LDL is potentiated as a result of retention in the arterial intima upon
      binding to extracellular matrix components and exposure to oxidative stress,
      leading to uptake by macrophages with subsequent foam cell formation. Such
      cholesterol-loaded, macrophage foam cells are active secretory cells, and exert
      multiple proinflammatory, proatherogenic and prothrombogenic effects during the
      initiation and progression of atherosclerotic plaques. Indeed, the secretory
      products of foam cells play a key role in the fragilization of lipid-rich
      plaques, leading ultimately to plaque rupture and the associated thrombotic
      complications. As the pharmacological modulation of dense LDL levels is of
      special interest, representing a new therapeutic approach in the treatment of
      atherogenic dyslipidaemia, we probed the biological mechanisms which underlie
      formation of dense LDL particles in combined hyperlipidaemia patients with a
      fibrate derivate, fenofibrate. Drug treatment (micronized fenofibrate, 200 mg.day
      1 for 8 weeks) induced significant reductions in the plasma concentrations of
      VLDL (-37%; P < 0.005), and of dense LDL (-21.5%; P < 0.05), with simultaneous
      increase in HDL-cholesterol (+19%; P < 0.0001). An endogenous assay of
      cholesteryl ester transfer from cardioprotective HDL to atherogenic,
      apolipoprotein B-containing lipoproteins (VLDL and LDL) revealed marked reduction
      (-38%) in cholesterol ester transfer from HDL to VLDL upon fenofibrate treatment,
      whereas no modification in the low rate of cholesteryl ester transfer between HDL
      and LDL was detected. Simultaneously, however, the LDL profile in combined
      hyperlipidaemia patients, which is characterized by a predominance of small,
      dense LDL, was shifted towards the LDL subpopulation of intermediate density and
      larger size. Particles of the intermediate LDL subclass are avidly bound and
      degraded by the cellular LDL receptor which represents the major, non-atherogenic
      pathway for catabolism of LDL-cholesterol. Our findings indicate that the overall
      mechanism of the fenofibrate-induced modulation of the atherogenic dense LDL
      profile in combined hyperlipidaemia involves reduction in cholesteryl ester
      transfer from HDL to VLDL, together with normalization of the intravascular
      transformation of hepatic VLDL to receptor-active LDL of intermediate density.

PMID- 9519340
TI  - An overview of reverse cholesterol transport.
AB  - Reverse cholesterol transport is a multi-step process resulting in the net
      movement of cholesterol from peripheral tissues back to the liver via the plasma
      compartment. Cellular cholesterol efflux is mediated by HDL, acting in
      conjunction with the cholesterol esterifying enzyme, lecithin: cholesterol
      acyltransferase. Cholesteryl ester accumulating in HDL can then follow a number
      of different fates: uptake in the liver in HDL containing apolipoprotein
      (particle uptake) by LDL receptors, selective uptake of HDL cholesteryl ester in
      liver or other tissues involving scavenger receptor B1, or transfer to
      triglyceride-rich lipoproteins as a result of the activity of cholesteryl ester
      transfer protein, with subsequent uptake of triglyceride-rich lipoprotein
      remnants in the liver. Recently, we and others have taken a molecular approach to
      analysing the different components of reverse cholesterol transport, by over- or
      under-expression of individual molecules in induced mutant mouse models, or by
      the study of human mutations involving molecules of reverse cholesterol
      transport. Such studies reveal that over-expression of the major HDL apoprotein,
      apolipoprotein A-I, is clearly anti-atherogenic. However, over- or under
      expression of molecules such as cholesteryl ester transfer protein, which have
      opposite effects on HDL levels and reverse cholesterol transport, suggest that
      both HDL levels as well as the dynamics of cholesterol movement through HDL are
      involved in the anti-atherogenic actions of HDL.

PMID- 9519341
TI  - Triglycerides and cardiovascular disease. A focus on clinical trials.
AB  - Observational studies, both case control and prospective, have routinely
      identified elevated triglycerides as a univariate predictor of cardiovascular
      disease, especially coronary heart disease, and in several studies this
      association persists in multivariate analysis. However, experimental information
      from clinical trials is required for clinical guidelines. Many clinical trials in
      dyslipidaemia have employed interventions with only minor effects on
      triglycerides. Five trials have used pharmaceutical agents with significant
      triglyceride effects and have correlated the clinical or angiographic benefit
      observed with the change in various lipid or lipoprotein components. In three of
      these five trials, the benefit for various coronary disease endpoints was more
      closely associated with triglyceride reductions than with changes in other lipids
      and lipoproteins. A sixth trial showed reduced coronary disease progression with
      treatment despite no change in LDL cholesterol. Reduction in triglycerides may
      result in direct benefit for coronary disease. Clinical trials employing
      pharmacological agents with significant effects on triglycerides should correlate
      clinical and/or angiographic benefit with observed lipid and lipoprotein changes,
      as well as any changes in non-lipid risk factors such as fibrinogen.

PMID- 9519342
TI  - Triglyceride-rich lipoproteins and progression of atherosclerosis.
AB  - AIMS: To present data from the Cholesterol Lowering Atherosclerosis Study (CLAS)
      and the Monitored Atherosclerosis Regression Study (MARS) demonstrating the
      relationship between triglyceride-rich lipoproteins and progression of
      atherosclerosis. METHODS AND RESULTS: CLAS and MARS were randomized, placebo
      controlled, arterial imaging trials designed to determine the effects of lipid
      lowering on the progress of atherosclerosis using coronary angiographic and
      carotid arterial wall intima-media thickness measurement end points. Included in
      each of these trials were specific measurements of triglyceride-rich lipoproteins
      in addition to the traditional lipid measurements. CONCLUSIONS: CLAS and MARS
      indicate that specific triglyceride-rich lipoproteins such as VLDL, IDL,
      apolipoprotein B-containing lipoprotein particles (i.e. lipoprotein Bc), and
      markers of triglyceride-rich lipoprotein metabolism (i.e. apolipoprotein C-III)
      are significantly related to progression of atherosclerosis. These specific
      triglyceride-rich lipoproteins are associated with the progression of
      atherosclerosis independently of HDL cholesterol levels. Importantly, there
      appears to be a differential effect of triglyceride-rich lipoproteins and
      cholesteryl-ester rich lipoproteins (i.e. LDL cholesterol) on the progression of
      mild/moderate and severe coronary artery lesions, respectively. This association
      not only suggests that certain risk factors may act early and others late in the
      athersclerotic process, but that triglyceride-rich lipoproteins are associated
      with progression of the lesions (mild/moderate lesions) which are predominantly
      responsible for clinical coronary events.

PMID- 9519343
TI  - Coronary heart disease risk factors in women.
AB  - Despite the obvious predominance of coronary heart disease in middle-aged men,
      cardiovascular disease including coronary heart disease and cerebrovascular
      accidents is currently the major cause of death in women (54% cardiovascular
      mortality, 46% coronary mortality; 28% of all deaths). Before menopause, coronary
      heart disease is infrequent which suggests that female hormones and metabolism
      offer protection. Without hormone replacement therapy after menopause women may
      develop coronary atherosclerosis. Ageing is among the non-modifiable risk factors
      for coronary heart disease in women, while genetic predisposition and
      environmental factors remain controversial. The modifiable risk factors are
      mostly common to both sexes and include heavy cigarette smoking (especially in
      women under oral contraception) dyslipidaemia, high blood pressure, and diabetes;
      some factors are peculiar to women. The delayed onset of coronary heart disease
      in women, roughly 10 years later than in men, and greater feminine longevity (81
      years vs 74 in men on average) points to the potential benefit of post-menopause
      hormone replacement therapy together with reduction of other modifiable risk
      factors. After menopause, the protective HDL cholesterol decreases whereas high
      LDL cholesterol, high triglycerides and high blood pressure are major risk
      factors for coronary heart disease as well as for cerebrovascular accident. The
      role of hormone replacement therapy in the prevention of cardiovascular disease
      in women is still controversial despite the results of meta-analyses which
      suggest a 25% to 44% reduction in coronary heart disease following oestrogen
      therapy alone or in combination with progestogen, depending on the hormonal
      regime. In conclusion, menopause, now considered as the marker for the end of
      natural protection against coronary heart disease, should be followed by early
      and prolonged combined hormone replacement therapy in order to reduce the low
      compliance with long-term hormone replacement therapy.

PMID- 9519344
TI  - Classical risk factors and emerging elements in the risk profile for coronary
      artery disease.
AB  - The prevention of coronary artery disease is based on the control of several
      factors associated with a disease or clinical condition and suspected to play a
      pathogenetic role, defined as 'risk factors'. Smoking is a powerful risk factor
      for coronary artery disease, with risk of events increasing in relation to the
      number of cigarettes smoked daily. Smoking cessation is associated within 3-4
      years, with a significant reduction in cardiovascular risk. Hyperlipidaemia is a
      powerful predictor of coronary disease with a strong, independent, continuous and
      graded positive association between cholesterol levels and risk of coronary
      events. Several large studies have shown the benefit of cholesterol reduction,
      and there is clear evidence of the efficacy of statins in the reduction of events
      in primary and secondary prevention. Hypertension is a significant, strong and
      independent risk factor for coronary artery disease morbidity and mortality and
      the reduction of events and mortality by antihypertensive treatment is well
      documented. Obesity is associated with an increase in all-cause mortality and
      cardiovascular mortality, with a particularly high risk for subjects with central
      obesity. Central obesity is also part of the so-called 'metabolic X syndrome'
      including insulin resistance, which appears to be associated with a particularly
      high risk of coronary artery disease. Type 1 and type 2 diabetes mellitus are
      associated with an increased risk of cardiovascular disease, especially in women.
      Several studies have shown that good metabolic control and multifactorial risk
      factor reduction significantly lower the coronary risk in these patients. Recent
      evidence is accumulating that some clotting factors (fibrinogen, factor VII, von
      Willebrand factor) and fibrinolytic factors (t-PA and PAI-1) are associated with
      an increased risk of coronary artery disease. The European Concerted Action on
      Thrombosis (ECAT) showed that the levels of fibrinogen, von Willebrand factor
      antigen, and t-PA antigen are independent predictors of subsequent coronary
      syndromes in patients with angina pectoris, and that low fibrinogen is associated
      with a low risk of events despite high cholesterol levels. Post-menopausal status
      is associated with increased risk of coronary artery disease, particularly when
      menopause is premature (before the age of 45) or abrupt (surgical). There is
      strong, thought not yet completely definite evidence that post-menopausal hormone
      replacement therapy may significantly reduce the risk of events and improve
      survival. Hyperhomocysteinaemia is an emerging risk factor independently
      associated with an increased risk of coronary artery disease, cerebral vascular
      disease, and peripheral vascular disease. The administration of vitamin B6, B12
      or folate seems to be useful and is currently under further evaluation. Recently,
      attention has been focused on the correlation between coronary artery disease and
      genetic factors, such as ACE gene polymorphism or the gene polymorphism for the
      IIIa-moiety of the platelet fibrinogen receptor IIb-IIIa. In primary prevention,
      control of the major risk factors mainly in patients with clustered factors will
      substantially reduce the risk of ischaemic events. Secondary prevention of CHD is
      based on: aggressive behavioural advice, blood pressure reduction in
      hypertensives, good metabolic control of diabetes, and cholesterol reduction.
      Aspirin, beta-blockers, ACE inhibitors, and oral anticoagulants, may be useful in
      selected patients.

PMID- 9519345
TI  - Overview of fenofibrate.
AB  - Fenofibrate is a broad spectrum lipid-lowering agent able to produce substantial
      reductions in plasma triglyceride and low density lipoprotein (LDL) and an
      increase in high density lipoprotein (HDL). It acts to promote the clearance of
      chylomicrons and very low density lipoproteins and can correct abnormalities in
      the LDL subfraction profile with a shift away from small, dense LDL. The drug is
      of particular use in correcting the atherogenic lipoprotein phenotype seen
      commonly in subjects with coronary heart disease. Recent investigations have
      revealed its likely mechanism of action at the molecular level. Fenofibrate binds
      to peroxisome proliferator activated receptor and initiates a sequence of events
      that leads to the reduction of apolipoprotein C-III synthesis in liver. This
      lipoprotein apoprotein inhibits the lipolysis and uptake of triglyceride-rich
      particles and suppression of its production causes enhanced catabolism. Further
      effects such as the changes in LDL and HDL follow from this primary action.

PMID- 9519346
TI  - Oxidative stress during myocardial ischaemia and heart failure.
AB  - Oxidative stress is a condition in which oxidant metabolites exert toxic effects
      because of their increased production or an altered cellular mechanism of
      protection. The heart needs oxygen but it is also susceptible to oxidative
      stress, which occurs during post-ischaemic reperfusion, for example. Ischaemia
      causes alterations in the defence mechanisms against oxygen free radicals. At the
      same time, production of oxygen free radicals increases. In man, there is
      evidence of oxidative stress during surgical reperfusion of the whole heart, or
      after thrombolysis, and it is related to transient left ventricular dysfunction
      or stunning. At present, there are few data on oxidative stress in the failing
      heart. It is not clear whether the defence mechanisms of the myocyte are altered
      or whether the production of oxygen free radicals is increased, or both. Recent
      data have shown a close link between oxidative stress and apoptosis. Importantly,
      tumour necrosis factor causes a rapid rise in intracellular reactive oxygen
      intermediates and apoptosis. This series of events is not confined to the
      myocytes, but also occurs at the level of endothelium, where tumour necrosis
      factor causes expression of inducible nitric oxide synthase, production of the
      reactive radical nitric oxide, oxidative stress and apoptosis. The immunological
      response to heart failure may result in endothelial and myocyte dysfunction
      through oxidative stress-mediated apoptosis. A better understanding of these
      mechanisms may lead to novel therapeutic strategies.

PMID- 9519347
TI  - Prevention of heart failure progression: current approaches.
AB  - Heart failure results from damage and stress to the myocardium whatever the
      aetiology. An increase in stress by cardiac overload is initially overcome by
      compensatory mechanisms that maintain blood pressure through a combination of the
      sympathetic nervous system and the renin-angiotensin-aldosterone system. These
      mechanisms may also alter myocyte function and induce progressive cell death and
      replacement by fibrous tissue. Disease therapy must reduce cardiac loading and
      avoid blood pressure control by mechanisms that have deleterious effects. Therapy
      includes diuretics, vasodilators and alpha- and beta-adrenergic blockade.
      Complete blockade of all receptors involved in the adverse effects of
      neurohormonal stimulation might represent an ultimate therapy objective, and
      improve subsequent prognosis. Large clinical trials are in progress to determine
      the therapy of choice in the prevention of progression of heart failure.

PMID- 9519348
TI  - Carvedilol: preclinical profile and mechanisms of action in preventing the
      progression of congestive heart failure.
AB  - Many pathophysiological processes are activated in patients with congestive heart
      failure, and several of these have been implicated in the progression of the
      disease. The most important processes to be activated in heart failure are the
      neurohormonal systems, which include the reninangiotensin system, the sympathetic
      nervous system and the endothelin system. In addition to the neurohormonal
      systems, the formation of reactive oxygen free radicals is increased in
      congestive heart failure. It has been proposed that the activation of
      neurohormonal pathways and the formation of oxygen free radicals ultimately lead
      to the activation of a family of transcription factors that are involved in
      cardiac and vascular remodelling which are hallmarks of congestive heart failure.
      In addition, the formation of oxygen free radicals has been implicated in the
      process of apoptosis, or programmed cell death, which may contribute to the
      continued loss of myocardial cells resulting in progressive decreases in left
      ventricular function, while at the same time contributing to the cardiac
      remodelling process which subsequently creates a pro-arrhythmic environment in
      the myocardium. Carvedilol is a novel multiple-action neurohormonal antagonist
      that has been shown to be effective in the management of congestive heart
      failure. Carvedilol also possesses a number of additional activities which may
      inhibit many of the chronic pathophysiological processes that are involved in the
      progression of congestive heart failure.

PMID- 9519349
TI  - Effects of neurohormonal antagonism on symptoms and quality-of-life in heart
      failure.
AB  - Increased mortality and reduced functional capacity are the two main
      characteristics of chronic heart failure. Activation of the renin-angiotensin and
      sympathetic systems has a primary role in the progressive worsening of heart
      failure and increased mortality of patients. In addition, both systems may be
      important in the pathogenesis of exercise intolerance, although there is only a
      weak relationship between neurohormonal activation and exercise capacity. While
      neurohormonal antagonists, such as angiotensin-converting enzyme (ACE) inhibitors
      and beta-blockers, consistently improve the prognosis of patients with heart
      failure, their effects on exercise tolerance have often been less significant.
      This problem has been emphasized by the introduction of beta-blockers for the
      therapy of heart failure. Beta blockade results in a significant improvement in
      left ventricular function during rest and exercise. However, the reduction in
      chronotropic response to exercise as well as the metabolic changes caused by
      these agents in skeletal muscle may result in an apparent lack of change in
      maximal functional capacity. This effect is particularly important with the new
      third generation non-selective beta-blockers. The pronounced anti-adrenergic
      activity of these compounds accounts for their greater negative chronotropic
      effect and relates to the lack of improvement in peak oxygen consumption (VO2).
      Submaximal exercise testing can be used to assess changes induced by these
      agents. However, even the six-minute walk test may act as an almost maximal test
      in patients with advanced heart failure: moreover, the measurement of submaximal
      exercise duration may be sensitive enough to detect changes in single-centre
      trials, but not in multicentre trials. To date, direct assessment of symptoms by
      both patient and physician is still the most sensitive tool to monitor changes in
      functional status with non-selective beta-blockers. Thus, an accurate method of
      measuring patients' symptoms, in addition to the clinical examination, is still
      necessary when neurohormonal antagonists are used in patients with chronic heart
      failure.

PMID- 9519350
TI  - Left ventricular remodelling and improved long-term outcomes in chronic heart
      failure.
AB  - Several targets for heart failure therapy may be met through different mechanisms
      which are not necessarily associated. In the Australia/New Zealand Heart Failure
      Research Collaborative Group Study, patients with chronic stable heart failure of
      ischaemic aetiology on treatment including ACE inhibitors were randomized to
      treatment with either the vasodilator beta-blocking drug carvedilol or placebo.
      At 12 months, symptoms and exercise performance were unchanged, but ejection
      fraction increased significantly with carvedilol treatment; at 20 months, the
      rate of death and hospitalization was also significantly reduced in the
      carvedilol-treated group. In a sub-study using two dimensional echocardiography,
      progressive left ventricular (LV) dilatation occurred in the placebo group,
      compared with significant reductions in LV volumes with the carvedilol treatment
      group. An overview of all available carvedilol trial data showed the odds of
      death reduced by one-half with treatment (OR 0.51, 95% CI 0.33-0.77, 2P =
      0.0014). Thus, improved LV remodelling occurs with carvedilol treatment in heart
      failure and is associated with improved long-term outcomes including survival.
      Improved LV function may, in part, mediate the survival benefit of carvedilol and
      provide a reliable surrogate for long-term outcomes.

PMID- 9519351
TI  - Do beta-blockers prolong survival in chronic heart failure? A review of the
      experimental and clinical evidence.
AB  - The results of both experimental studies and clinical trials indicate that
      prolonged activation of the sympathetic nervous system can adversely affect the
      course of heart failure, and that this deleterious effect can be attenuated with
      the use of beta-blocking agents. Studies with beta-1 selective agents such as
      metoprolol and bisoprolol, have demonstrated that beta-blockers can reduce the
      risk of worsening heart failure but have shown little or equivocal effect on
      survival. In contrast, recent trials with non-selective vasodilating beta
      blockers (i.e. carvedilol) have reported a reduction in the risk of both death
      and hospitalization. It is uncertain, however, whether these survival effects
      represent a class effect of beta-blockers or a specific effect of carvedilol.
      Carvedilol antagonizes several biological mechanisms (not blocked by metoprolol
      or bisoprolol) that may be important in mediating the progression of heart
      failure. In three meta-analyses, the survival effects of non-selective
      vasodilating beta-blockers (primarily carvedilol) were greater than those of beta
      1 selective non-vasodilating beta-blockers. A clear answer to the question as to
      whether mortality reduction is a class effect of beta-blockers will be provided
      by several large-scale survival trials, which are currently in progress.

PMID- 9519352
TI  - Prevention of worsening heart failure: future focus.
AB  - For decades heart failure therapy has focused on symptomatic treatment, whereas
      preventive aspects have received less attention. However, 10 years of large
      controlled trials has provided insight into the potential of certain agents to
      prevent or delay the onset or worsening of heart failure. Such agents include ACE
      inhibitors and, in addition to the former beta-blockade, the vasodilator beta
      blocking agent carvedilol, which possesses additional properties such as
      antioxidant effects. In contrast, drugs which typically are used to improve heart
      failure symptoms, such as diuretics, do not necessarily lead to prevention of
      (worsening) heart failure. Multiple mechanisms underlie worsening of left
      ventricular dysfunction and heart failure and have been, or may well be,
      instrumental in the development of novel preventive therapies of this syndrome.
      Principal mechanisms include: cardiac and vascular remodelling; neurohormonal and
      cytokine activation; hibernation and stunning; ischaemia-induced free radical
      formation; apoptosis; abnormalities in the cardiac membrane receptor, downstream
      signalling pathways, in intracellular calcium homeostasis, and sensitivity. As
      these mechanisms interact, leading to progression of heart failure, they provide
      opportunities for novel pharmacotherapeutic approaches. It is to be expected that
      many drugs currently in development will be added to the list of accepted heart
      failure therapy. As polypharmacy is likely to result and is to some extent
      unavoidable, the future challenge will be to detect the usefulness of alternative
      treatments to currently accepted therapy to prevent worsening of heart failure,
      enabling a more individualized and hence effective approach in each patient.

PMID- 9519353
TI  - Immunologic aspects of bovine injectable collagen in humans. A review.

PMID- 9519354
TI  - The importance of prognostic factors in the interpretation of two EORTC
      metastatic prostate cancer trials. European Organization for Research and
      Treatment of Cancer (EORTC) Genito-Urinary Tract Cancer Cooperative Group.
AB  - INTRODUCTION AND OBJECTIVES: The EORTC conducted two randomized phase III trials
      of maximal androgen blockade (MAB) in 695 patients with metastatic prostate
      cancer. Trial 30,843 compared orchidectomy or buserelin to buserelin plus
      cyproterone acetate and showed no significant difference in survival while trial
      30,853 showed that Zoladex plus flutamide had a significantly longer survival
      than orchidectomy. Reasons for this discrepancy were sought. METHODS: In order to
      determine whether differences in patient characteristics could explain these
      possibly contradictory results, a Cox proportional hazards regression model was
      used to identify prognostic factors for survival in each study. Patients were
      divided into risk groups (good or poor prognosis with 3.5 and 1.75 years' median
      survival, respectively) based on their alkaline phosphatase, hemoglobin,
      performance status, pain score, T category and G grade at entry on study.
      RESULTS: The survival advantage of MAB in 30,853 was limited to patients with a
      good prognosis (164/302 (54%) of the patients). In 30,843, only 93/337 patients
      (28%) had a good prognosis so there were insufficient data to draw separate
      conclusions in these patients. Despite the limitations of subgroup analyses,
      these results show that patients in 30,843 had on the average a worse prognosis
      than patients in 30,853. Hence there were fewer good prognosis patients who could
      potentially benefit from MAB, thus providing one possible explanation for the
      overall negative conclusion. CONCLUSIONS: These studies once again underline the
      importance of taking into account patient characteristics when designing and
      interpreting metastatic prostate cancer trials. They also provide criteria which
      may be used to define risk groups as part of a protocol's patient eligibility
      criteria. In the design of future trials assessing MAB, a sufficient number of
      good prognosis patients should be entered to reliably assess treatment efficacy
      in this subgroup.

PMID- 9519355
TI  - Maximal androgen blockade: final analysis of EORTC phase III trial 30853. EORTC
      Genito-Urinary Tract Cancer Cooperative Group and the EORTC Data Center.
AB  - OBJECTIVES: This prospective, randomized phase III study was initiated to compare
      the efficacy and side effects of bilateral orchiectomy versus a combination of a
      luteinizing hormone-releasing hormone agonist depot formulation, goserelin
      acetate (3.6 mg s.c. once every 4 weeks) and flutamide (250 mg 3 x daily) in
      patients with metastatic prostate cancer. METHODS: Relative treatment efficacy
      was assessed by comparing the two treatment groups with respect to response, time
      to first progression, progression-free survival, duration of survival and time to
      death due to malignant disease. RESULTS: There was a difference in response only
      with respect to a more frequent decrease to normal of the serum prostate acid
      phosphatase in patients assigned to maximal androgen blockade treatment.
      Additionally, maximal androgen blockade treatment showed significantly better
      results for duration of survival (p = 0.04), time to death due to malignant
      disease (p = 0.008), time to first progression (p = 0.009) and progression-free
      survival (p = 0.02). The most frequent side effects for both treatments included
      hot flushes and gynaecomastia. CONCLUSIONS: Increased time to progression and
      duration of survival is achieved by the combination of flutamide and goserelin
      when compared to bilateral orchiectomy.

PMID- 9519356
TI  - Maximum androgen blockade using LHRH agonist buserelin in combination with short
      term (two weeks) or long-term (continuous) cyproterone acetate is not superior to
      standard androgen deprivation in the treatment of advanced prostate cancer. Final
      analysis of EORTC GU Group Trial 30843. European Organization for Research and
      Treatment of Cancer (EROTC) Genito-Urinary Tract Cancer Cooperative Group.
AB  - This is the final analysis of EORTC GU Group Trial 30843 in which the treatment
      of advanced, metastatic prostate cancer with a combination of the LHRH agonist
      buserelin (nasal spray) and cyproterone acetate (Androcur), either continuously
      of only during the first 2 weeks, was compared with orchidectomy. There was no
      significant difference between the three arms as far as response rate, time to
      progression (subjective and objective) and duration of survival are concerned.
      Retrospective stratification according to the most important prognostic factors
      did not change the conclusions. Possible reasons for the difference with trial
      30853, which used the same entry criteria but compared goserelin and flutamide
      with orchidectomy, are discussed. Reasons for using cyproterone acetate in
      combination treatment are the prevention of flare of the disease after LHRH
      agonists only and the prevention/reduction of toxicity in the form of hot
      flushes.

PMID- 9519357
TI  - Are non-steroidal anti-androgens appropriate as monotherapy in advanced prostate
      cancer?
AB  - OBJECTIVES: To evaluate the efficacy of non-steroidal anti-androgen monotherapy
      in the treatment of advanced prostate cancer. METHODS: The pertinent literature
      regarding the use of nilutamide, flutamide, and bicalutamide as monotherapy in
      the treatment of prostate cancer has been reviewed. RESULTS: The clinical utility
      of non-steroidal antiandrogen monotherapy is currently under investigation. As
      with other endocrine therapies, this approach appears to provide effective
      palliation of symptoms, but offers certain quality-of-life benefits, including
      preservation of libido and sexual potency, issues which may be important in
      certain patients, particularly younger men. Available data indicate that
      flutamide may be as effective as orchidectomy in terms of prolonging progression
      free survival in selected patients. Nilutamide has been less extensively
      investigated, but the clinical utility of this agent, except for use in combined
      therapy, would appear to be somewhat limited by a high incidence of drug-related
      side effects. Bicalutamide, however, is well tolerated as monotherapy and appears
      to be as effective as castration in patients with locally advanced non-metastatic
      disease. In metastatic disease, the improved subjective response and quality of
      life gains with bicalutamide may outweigh the slightly inferior survival.
      CONCLUSION: These promising preliminary findings, a number of issues remain to be
      determined before non-steroidal antiandrogen monotherapy can be considered to be
      routine clinical practice. These include optimum indication and dosage, long-term
      clinical efficacy and tolerability, and response to second-line therapy.

PMID- 9519358
TI  - Prevalence and impact of incontinence and impotence following total prostatectomy
      assessed anonymously by the ICS-male questionnaire.
AB  - OBJECTIVES: The aim of this study was to assess the incidence of incontinence and
      impotence in patients following total prostatectomy and assess the impact their
      symptoms have on their quality of life. PATIENTS AND METHODS: Between 1987 and
      1994, one surgeon performed retropubic total prostatectomies on 89 patients, of
      which 87 were available for follow-up. All patients were sent an ICS-male
      questionnaire. Patients' ages ranged from 49 to 73 years (median 65). The
      interval between surgery and completing the questionnaire ranged from 7 to 87
      months (median 22). RESULTS: The response rate was 95%. No patients reported
      incontinence pre-operatively. Postoperatively, 69% (57/83) of patients suffered
      to some degree of leakage of urine and 24% (29/83) used pads. Of these, 60% used
      1 pad per day, 15% 2 pads and 25% (5 patients) used 3 or more. Nocturnal
      incontinence was reported by 20% of patients. Urinary incontinence was considered
      a problem in only 34% (28/83) of patients. Sixty-five percent of patients using
      pads considered urinary leakage to be a problem, but only 1 considered it a
      serious problem. 89% claimed to have been potent prior to surgery. The overall
      postoperative potency rate was 41% (30/74) in those potent pre-operatively.
      However, 67% of patients reporting potency had severely reduced rigidity, and
      only 12% (9/74) achieved what they considered full erections. Ten percent of all
      patients considered postoperative impotence to be a serious problem, and 47%
      stated that it was not a problem at all. CONCLUSIONS: The incidence of
      incontinence and impotence following total prostatectomy is higher than earlier
      reports suggest, but the impact of these complications appears to be surprisingly
      low. These results allow patients to be given realistic expectations when
      counselled prior to this operation.

PMID- 9519359
TI  - Urethral recurrence of transitional cell carcinoma of the bladder. Predictive
      value of preoperative latero-montanal biopsies and urethral frozen sections
      during prostatocystectomy.
AB  - OBJECTIVE: The management of the male urethra after cystectomy for bladder cancer
      continues to be a dilemma. Patients who undergo a cystectomy require either
      urinary diversion or bladder substitution. Therefore, the use of the urethra to
      ensure voiding is important. On the other hand, the probable risk of urethral
      carcinoma recurrence is generally estimated at approximately 10%. The aim of this
      study was to assess the predictive value of preoperative urethral biopsies, and
      of frozen sections during cystoprostatectomy, in patients with invasive bladder
      cancer. METHODS: From 1982 to 1986, 118 male patients underwent a
      cystoprostatectomy for transitional cell carcinoma of the bladder. All patients
      underwent endoscopic latero-montanal biopsies 2 weeks preoperatively and urethral
      frozen cut section during radical prostatocystectomy. RESULTS: Carcinoma was
      observed in 12 patients on both examinations. All patients underwent en bloc
      urethrectomy during cystectomy. In the remaining 106 patients, the frozen cut
      margin was negative (including 9 with positive latero-montanal biopsies), and
      these patients had the urethra preserved. After a 10-year minimum follow-up, no
      recurrence was observed in these patients with negative frozen cut-section. No
      significant risk factors for urethral recurrence were found. Latero-montanal
      biopsies did not reveal a positive specificity, and this procedure was later
      abandoned in our institution (in 1986). CONCLUSIONS: The urethral frozen section
      was the only guideline used for simultaneously performing the urethrectomy. All
      male patients with negative frozen cut sections should be considered candidates
      for bladder substitution. A prophylactic urethrectomy is only indicated in
      patients with carcinoma (minimum carcinoma in situ) in the frozen urethral margin
      section during cystectomy.

PMID- 9519360
TI  - Incidence of tumoural pathology in horseshoe kidneys.
AB  - OBJECTIVES: To know the incidence of tumoural pathology among our cases of
      horseshoe kidney (HK), a congenital anomaly occurring in 0.25% of the population,
      as well as their prognostic factors and follow-up. METHODS: A total of 82
      patients admitted at our Centre between 1967 and 1996 with an HK diagnosis were
      retrospectively reviewed. We have collected a total of 10 cases of HK tumours. We
      analyse the clinical, diagnostic, surgical and evolutionary peculiarities of the
      different HK tumour aetiologies, as compared with those described in literature.
      RESULTS: Our experience is based on 10 patients-5 adenocarcinomas, 4 transitional
      cell carcinomas and a Wilms' tumour. CONCLUSIONS: We have observed that in the
      case of transitional cell carcinomas, the diagnosis is generally made at an
      advanced stage. The prognosis of the tumorous disease depends upon the same
      prognostic factors as in the case of normal kidneys. Renal adenocarcinoma is the
      kind of tumour most frequently associated with HKs. Its incidence among the HK
      cases is not greater than among the normal population. Conservative local
      treatment criteria for adenocarcinoma should be valid for HKs as well.

PMID- 9519361
TI  - Lymph node metastasis in patients with carcinomas of the renal pelvis and ureter.
AB  - OBJECTIVES: We evaluated the clinical significance of lymph node metastasis in
      patients with carcinomas of the renal pelvis and ureter. METHODS: 68 patients
      without distant metastasis were included in this study. Multivariate analysis by
      Cox's proportional hazards model was applied to detect the prognostic factor(s).
      RESULTS: 12 patients (17.6%) had nodal involvement. More than 10% of the patients
      with pT1-2 showed nodal metastasis. Preoperatively determined clinical factors
      were not a predictive factor for nodal involvement. Nodal metastasis was the only
      significant negative prognostic factor for patient survival by multivariate
      analysis. CONCLUSIONS: Lymph node dissection is valuable to predict the clinical
      outcome of the patients with carcinoma of the renal pelvis and ureter. Attention
      should be paid to nodal status to select patients for conservative surgery.

PMID- 9519362
TI  - Value of nuclear morphometry for differentiating localized from metastatic renal
      cell carcinoma.
AB  - OBJECTIVE: To evaluate the feasibility of using nuclear morphometry of primary
      renal cell carcinoma to differentiate cases with localized tumors from those with
      metastases. METHODS: Using an interactive image analysis system, nuclear
      morphometry was performed on hematoxylin- and eosin-stained slides of 40 primary
      renal tumors. There were 18 cases with organ-confined disease and 22 with
      advanced stage. RESULTS: The most significant shape descriptor to differentiate
      between the two groups was mean nuclear regularity factor (889.5 +/- 24.4 vs.
      701.1 +/- 157.3, p = 0.00015). The combination of mean nuclear area and mean
      nuclear regularity factor enabled accurate prediction of metastatic potential in
      36 (85%) cases. CONCLUSION: Nuclear morphometry measured by image analysis
      provides prognostic information on patients with renal cell carcinoma.

PMID- 9519363
TI  - Unilateral laparoscopic retroperitoneal lymph node dissection for clinical stage
      I nonseminomatous germ cell testicular neoplasm.
AB  - OBJECTIVE: The aim of this study is to evaluate the reliability of laparoscopic
      retroperitoneal lymph node dissection (LRPLND) in the management of clinical
      stage I nonseminomatous germ cell tumors (NSGCT). METHODS: Since June 1993,
      unilateral LRPLND was performed in 6 patients diagnosed with clinical stage I
      NSGCT. All patients had undergone prior radical orchiectomy. The testicular
      cancer was left-sided in 3 cases and right-sided in the other 3 cases.
      Preoperative staging by means of tumor marker assessment, computerized tomography
      scan of the chest and abdomen and chest X-ray was unremarkable for metastatic
      disease. RESULTS: All procedures were accomplished without any complications in a
      mean time of 325 min (275-420 min). The estimated perioperative blood loss was
      minimal (< 50 ml), and none of the patients required blood transfusion. In the
      case of the first patient, the hospital stay was 18 days due to a widespread
      subcutaneous emphysema. In the remaining 5 cases, the average hospitalization was
      4.8 days, ranging from 4 to 6 days. The patients resumed normal activities within
      12-27 days (mean 16.16 days) postoperatively. The mean number of lymph nodes
      removed was 6.8, ranging from 5 to 9. Histologic examination of the dissected
      lymph nodes revealed microscopic metastases from embryonal carcinoma in 2
      patients. Both of these patients received adjuvant chemotherapy. The mean follow
      up period is 21.3 months, ranging from 6 to 36 months. To date, no relapses have
      been observed. CONCLUSION: In accordance with other reports, we believe that
      LRPLND is both feasible and effective. However, the definitive assessment of the
      efficacy and morbidity of this diagnostic procedure requires a larger and more
      comprehensive series as well as longer follow-up.

PMID- 9519364
TI  - Transcutaneous high-intensity focused ultrasound and irradiation: an organ
      preserving treatment of cancer in a solitary testis.
AB  - OBJECTIVES: The aim of this study was to determine the feasibility and safety of
      transcutaneous ablation of human testicular tissue by high-intensity focused
      ultrasound (HIFU). METHODS: Transcutaneous ablation of human testicular tissue by
      HIFU was performed with equipment previously developed for transrectal prostate
      ablation. This device utilizes a piezoceramic transducer operating at 4.0 MHz
      with a site-intensity of 1,600-2,000 W/cm2. To study the histological impact of
      transcutaneous HIFU, tests of 4 patients with prostate cancer were subjected to
      transcutaneous HIFU-therapy prior to scrotal orchiectomy in a phase I trial. In a
      phase II clinical trial, 4 patients with the typical sonographic pattern of a
      tumor in a solitary testis were treated with transcutaneous HIFU as a minimally
      invasive organ-preserving approach followed by a 6 weeks' course of prophylactic
      irradiation of the testis with 20 Gy. In all 4 patients, the contralateral testis
      had been previously removed for testis cancer. RESULTS: Histologically, HIFU
      treated areas exhibited signs of cellular necrosis in all cases (n = 4). The
      border between viable and necrotic tissue was extremely sharp comprising only 5-7
      cell layers. In the phase II clinical study, we aimed to ablate the entire cancer
      in a single therapeutic HIFU session. HIFU treatment was performed under general
      anesthesia. As negative side effects we observed a cutaneous thermolesion in 1
      individual. One patient refused to undergo postoperative irradiation and
      developed a local failure. This patient underwent radical orchiectomy. Another
      patient received two cycles of chemotherapy for a single suspicious
      retroperitoneal lymph node diagnosed 6 months after HIFU therapy. Three patients
      are tumor-free with a follow-up of 16, 23 and 31 months, respectively.
      CONCLUSIONS: This study demonstrates the feasibility and safety of transcutaneous
      testicular tissue ablation by HIFU. Despite the major drawback of this technique,
      i.e. that no tumor histology is obtained, we believe that transcutaneous HIFU
      followed by irradiation has the potential to be established as a minimally
      invasive treatment alternative to organ-preserving surgery for tumors in a
      solitary testis.

PMID- 9519365
TI  - Transurethral resection of the prostate and laser prostatectomy under local
      anesthesia.
AB  - OBJECTIVE: To perform transurethal resection of the prostate (TURP) and
      transurethral laser ablation prostatectomy (TULAP) under appropriate local
      anesthesia. PATIENTS AND METHODS: A total of 54 patients were examined in this
      study. We carried out TURP in 42 and TULAP in 12 of them under local anesthesia
      with lignocaine chloride. Patient's discomfort was recorded by means of a four
      point descriptive pain scale. RESULTS: We had perfect pain control in the
      majority of the patients. Patient's acceptance was very high. No patient required
      conversion to general anesthesia. Complications due to local anesthesia were not
      observed. CONCLUSION: We believe that ours is a simple, safe and effective
      procedure.

PMID- 9519366
TI  - Loss of urethrovaginal septum as a complication of exstrophy closure in girls.
AB  - PURPOSE: The aim of this study was to report complications involving
      paraexstrophy skin flaps in the female bladder exstrophy closure. MATERIALS AND
      METHODS: Bladder exstrophies in three female patients were initially closed using
      paraexstrophy skin flaps, with an osteotomy being performed in only 1 patient. A
      dehiscence occurred in all, and a reclosure was performed at a mean of 10 (range:
      7-18) months after the initial closure. RESULTS: Two patients underwent
      successful reclosure and are awaiting bladder neck reconstruction. The third
      patient, who had complete procidentia, had a bladder which failed to grow after
      successful reclosure and underwent augmentation cystoplasty. CONCLUSIONS: Closure
      of bladder exstrophy in female patients using paraexstrophy skin flaps can be
      associated with an increased complication rate and should be used judiciously in
      the exstrophy patient.

PMID- 9519367
TI  - Role of thermography in the diagnosis of undescended testes.
AB  - OBJECTIVES: The location of an undescended testis is important for the choice of
      therapy. Ultrasonography cannot serve as a stand-alone screening method in the
      management of the undescended testis because of its limited sensitivity and
      accuracy. The aim of this study was to clarify the diagnostic value of
      thermography in the patients with undescended testes. METHODS: We evaluated
      prospectively 28 patients with 36 undescended testes from January 1995 to
      December 1996. The patients' ages ranged from 16 to 39 months with a mean age of
      26.3 +/- 8.2 months. In addition to physical palpation by a pediatric surgeon,
      ultrasonography and thermography were performed for screening the locations of
      retained testes. RESULTS: The diagnostic rates were 63.9% (23/36) by palpation,
      65.7% (23/35) by ultrasonography and 54.5% (18/33) by thermography. The results
      of the three diagnostic methods showed no significant difference by Fisher's
      exact test. Of the 17 higher located testes (inguinal canal and above external
      ring) 7 were palpable, 8 were identified by ultrasonography, 10 were detected by
      thermography. Of the 7 nonpalpable testes and testes not detected by
      ultrasonography, 5, including 2 intra-abdominal testes, were identified by
      thermography. CONCLUSION: It is suggested that thermography can play a role in
      locating high undescended testes which are nonpalpable and not detected by
      ultrasonography.

PMID- 9519369
TI  - Analysis of a mutant androgen receptor offers a treatment modality in a patient
      with partial androgen insensitivity syndrome.
AB  - OBJECTIVES: In male pseudohermaphroditism patients, we have detected androgen
      receptor (AR) gene mutations as the underlying molecular defect. The properties
      of these mutant receptors regarding hormone binding and transactivation were
      characterized. In a newborn patient with partial androgen insensitivity syndrome
      caused by an AR gene point mutation, the functional analysis of the mutated AR
      offers a possible treatment modality. METHODS: Specific binding of
      dihydrotestosterone in the patient's genital skin fibroblasts, thermostability,
      and 5 alpha-reductase activity were evaluated. Furthermore, an AR gene mutation
      was detected by direct sequencing. The ability of the mutant receptor to activate
      androgen-responsive elements in the DNA was determined by recreating an AR
      expression vector and cotransfection experiments. RESULTS: The newborn patient
      with partial androgen insensitivity showed a qualitative and quantitative binding
      defect. A point mutation in the ligand binding domain was identified as the
      underlying cause. Transactivation assays demonstrated that increasing androgen
      concentration can restore the function of the mutated receptor completely.
      Therefore, the patient received androgen stimulation which resulted in good
      growth of his external genitalia and underwent surgical correction in the male
      direction. CONCLUSIONS: Diagnosis and therapy in affected patients will be
      improved identifying the molecular mechanisms that cause the various forms of sex
      ambiguity. Exact characterization of AR activation and function may offer a
      possible treatment modality in patients with the androgen insensitivity syndrome.
      Our results led to a surgical correction of our newborn patient in the male
      direction.

PMID- 9519368
TI  - The nitric oxide synthase/nitric oxide and heme oxygenase/carbon monoxide
      pathways in the human ureter.
AB  - OBJECTIVE: To investigate the nitric oxide synthase (NOS)/nitric oxide (NO) and
      heme oxygenase (HO)/carbon monoxide (CO) pathways in the human isolated ureter.
      METHODS: Immunohistochemical studies were performed. NOS activity was measured by
      monitoring the conversion of [3H]-arginine to [3H]-citrulline. Functional
      inhibitory effects mediated by NO and CO were assessed, and correlated with
      cyclic nucleotide levels. RESULTS: The overall innervation of the ureter was
      moderate, however more prominent in the distal segment. Relative to overall
      innervation, neuronal NOS-immunoreactive (-IR) nerves were few. In the submucosa,
      neuronal NOS-IR varicose nerves were found closely together with varicose nerves
      containing calcitonin gene-related peptide immunoreactivity. In the distal
      ureter, nerve trunks were demonstrated, expressing immunoreactivity for HO-2.
      Ca(2+)-dependent NOS activity was 53 +/- 13 pM/mg protein/h. In isolated
      preparations, NO decreased endothelin-1-induced contraction in a concentration
      dependent manner. In strips exposed to NO, there was a 6-fold increase of the
      cyclic GMP levels in comparison to control preparations (p < 0.001). CO exerted
      no effect on induced ureteral tone. CONCLUSIONS: Neuronal NOS- and HO-2-IR nerves
      can be demonstrated in the human ureter, where NO, but probably not CO, may
      contribute to the regulation of tone. Although the physiological roles for NO and
      CO remain to be established, the NOS/NO/cyclic GMP pathway may be a target for
      drugs producing relaxation of the human ureter. The richer innervation of the
      distal ureter may be of importance for the coordination of ureteral peristalsis
      and the motility of the ureterovesical junction.

PMID- 9519370
TI  - Genetic instability in renal cell carcinoma.
AB  - OBJECTIVE: To investigate the incidence of loss of heterozygosity (LOH) and
      microsatellite instability (MI) in human renal cell carcinoma (RCC), and to
      determine a possible activation of H-ras oncogene in these tumours via
      implication of its polymorphic regions within the first intron and 3' ends.
      METHODS: In the present study, we investigated the incidence of MI and LOH in 22
      RCCs, using a bank of 8 microsatellite markers located on chromosomes 2 (IL1A), 3
      (D3S1234), 8 (MYC), 14 (D14S51) and 17 (THRA1, D17S250, D17S579). We also studied
      the microsatellite DNA of the H-ras oncogene within the first intron (HRM) and
      the minisatellite DNA of the variable tandem repeat (VTR), which is located 1,000
      bp downstream of the H-ras gene and possesses enhancer activity, for genetic
      instability. Alterations of the 28-bp repetition core were studied employing
      restriction fragment length polymorphism analysis. RESULTS: MI and LOH were
      observed in 8 (4 MI and 4 LOH) out of 22 (18%) specimens at 3p21.1-p14.2 and
      17q21, indicating the presence of putative tumour suppressor genes (TSGs) at
      these loci. Alterations of the 28-bp repetition core of H-ras VTR were found in 2
      out of 22 cases (9%), while point mutations of the same repetition core were
      detected in only 1 case (5%). Additionally, 1 case (5%), showed LOH. CONCLUSIONS:
      Our results indicate that genetic instability is a detectable phenomenon in human
      RCC and it might be associated with the development of the disease. LOH at 3p21.1
      p14.2 and 17q21 suggests that important TSGs may be located on these chromosomal
      regions involved in the tumorigenesis or progression of RCC. Considering the fact
      that the DNA sequence of this VTR region contains a target area for transcription
      and other regulation factors of H-ras gene expression, these findings could be of
      importance as regards the involvement of this gene in the process of
      carcinogenesis in RCC.

PMID- 9519371
TI  - Biomechanical properties of the internal spermatic vein in the normal population
      and patients with left-sided varicocele testis.
AB  - OBJECTIVE: The aim of the study was to investigate a possible decreased strength
      of the wall of the left internal spermatic vein between patients with varicocele
      testis and controls. MATERIALS: From 14 patients with varicocele testis, 2 cm of
      the vein was obtained during operation per varicocele and compared to samples of
      the left internal spermatic vein taken from the same anatomical localization of
      19 patients with no varicocele testis or other conditions with relation to the
      scrotum; additionally, samples from the right internal spermatic vein similar to
      those described above were taken from 12 patients. The biomechanical properties
      of ring-shaped venous specimens were investigated by loading the specimens at a
      constant deformation rate until rupture. MAIN RESULTS: The regression
      coefficient, standard error and p value revealed no significant differences in ID
      (diameter), UC (unit collagen/ID), E-max (ultimate extensibility), Max (maximum
      strength), Tan-a (maximum stiffness), E-fail (relative failure energy). The trend
      to significance was shown in ID between the varicocele and left-sided veins (p =
      0.05) and between left- and right-sided veins (p = 0.05). CONCLUSIONS: These
      biomechanical tests of the spermatic veins from healthy subjects and patients
      operated for varicocele showed that biomechanical differences were associated
      with age and could play a part in the development of varicocele testis in an age
      matched group.

PMID- 9519372
TI  - Treatment of bilateral renal cell cancer and multiple lung metastasis: nephron
      sparing surgery and resection of lung tumors after interleukin-2 therapy.
AB  - We report a case of bilateral renal cell cancer and multiple lung metastasis who
      was first treated with left radical nephrectomy and nephron-sparing surgery of
      the right kidney. Consecutive interleukin-2 administration achieved partial
      response in lung disease and residual tumors were surgically removed. The disease
      free state has continued for 33 months.

PMID- 9519373
TI  - Expression of fibroblast growth factor receptor in adult mouse utricle damaged by
      streptomycin sulfate.
AB  - The expression of fibroblast growth factor (FGF) receptor was investigated in
      adult mouse utricles damaged by streptomycin sulfate using confocal laser
      scanning microscopy (CLSM). The nerve endings in the mouse utricles could be
      detected by the immunoreactivity of neurofilament by CLSM. In the utricles of
      control adult mice, little expression of FGF receptor could be detected by a
      method of double staining for FGF receptor and neurofilament immunoreactivities.
      However, the expression of FGF immunoreactivity increased in the nerve endings of
      the damaged utricles. This result suggests that FGF is probably related to the
      synaptic plasticity in the adult mouse utricles.

PMID- 9519374
TI  - Studies of cochlear blood flow in guinea pigs with endolymphatic hydrops.
AB  - Laser Doppler flowmetry was used to assess cochlear blood flow (CoBF) in guinea
      pigs with experimental endolymphatic hydrops following intravenous infusion of 5
      types of drugs: 50% glycerol, 70% isosorbide, 20% mannitol, 7% sodium
      bicarbonate, and 1% diphenidol. The magnitude of the CoBF changes following
      infusion tended to be smaller in the hydropic ears than in the normal control
      ears. A significant reduction in CoBF changes was observed in hydropic ears
      infused with isosorbide and sodium bicarbonate. These results suggest that the
      cochlear microvascular sensitivity to various stimuli such as drug infusion is
      reduced in hydropic ears. This may result from atrophy of the stria vascularis
      which is often observed in the hydropic ears of guinea pigs. Thus it seems likely
      that the same reaction occurs in the inner ear of patients with Meniere's disease
      in whom atrophy of the stria vascularis is also presumed to exist in conjunction
      with extensive endolymphatic hydrops. Therefore, it seems probable that the
      function of the microvasculature of the stria vascularis is impaired in the inner
      ear of patients with Meniere's disease, resulting in the slow progressive
      deterioration of the inner ear with time.

PMID- 9519375
TI  - Staphylococcus aureus exotoxin has limited and transient effects on cochlear
      electrophysiology.
AB  - Seven ears of Sprague-Dawley rats were exposed to 20 microliters Staphylococcus
      aureus exotoxin suspension by injection via the tympanic membrane into the round
      window niche. Another 6 ears were exposed to 20 microliters broth as controls.
      ABR was performed in the interval 2-31.5 kHz immediately before and 1, 2, 5, 7
      and 10 days after the exposure. Although threshold changes could be found in the
      toxin-exposed group but not the control group in the frequency range 10-20 kHz,
      there were only statistically significant threshold changes--at 31.5 kHz--on the
      1st, 2nd, 5th, and 7th days after the exotoxin injection. S. aureus exotoxin has
      minor transient but reversible effects on the inner ear, causing chiefly high
      frequency threshold and latency changes.

PMID- 9519376
TI  - Memantine suppresses the glutamatergic neurotransmission of mammalian inner hair
      cells.
AB  - The glutamatergic synapses between inner hair cells and afferent neurons seem to
      be involved in pathophysiological conditions of the cochlea. The excessive
      release of glutamate from inner hair cells during noise trauma and ischemia
      affects the afferent neurons. It is possible that in tinnitus outer hair cell or
      inner hair cell dysfunction or damage leads to an altered spontaneous release of
      glutamate from inner hair cells. Thus, the pharmacological modulation of
      glutamatergic neurotransmission could be of great value in the therapy of certain
      inner ear diseases. Recently, it has been discovered that the spasmolytic drug
      memantine has antiglutamatergic properties. As a possible drug for inner ear
      diseases, we were interested in the action of memantine on the neurotransmission
      of inner hair cells. With the aid of microiontophoretic techniques we were able
      to show a strong depressing effect on spontaneous activity as well as on
      glutamate-induced activity. This effect seems to be mediated by a blockade of N
      methyl-D-aspartate (NMDA) receptors as memantine showed a strong inhibiting
      effect on NMDA-induced activity but not on AMPA-induced activity. These results
      recommend memantine for the treatment of inner ear diseases, e.g. especially
      tinnitus.

PMID- 9519377
TI  - Experimental hemispherectomy and hemicerebellectomy and their influence on
      vestibular habituation.
AB  - The aim of the study was to estimate the influence of hemispherectomy and
      hemicerebellectomy on acquisition and retention of vestibular habituation in
      pigeons. The habituation training was performed using a rotatory test. The
      frequency of head nystagmus and postural reflexes was examined before and after
      acquisition of habituation and some days later, for the evaluation of the
      retention process. Our results suggested that the hemispherectomy did not inhibit
      the acquisition of habituation but retention of this phenomenon was shorter at
      that time. The hemicerebellectomy made it impossible to reveal the vestibular
      habituation.

PMID- 9519378
TI  - The presence of platelet-activating factor-acetylhydrolase in human middle ear
      effusions.
AB  - Factors related to inflammation, including platelet-activating factor (PAF),
      apparently have a role in chronic otitis media with effusion. PAF is metabolized
      to the biologically inactive lyso-PAF by the enzyme PAF-acetylhydrolase (PAF-AH).
      We have obtained evidence that PAF-AH activity is present in human middle ear
      effusions in patients with chronic otitis media with effusion. The present study
      revealed the enzyme in human middle ear effusions to be the plasma type PAF-AH.
      We suggest that PAF-AH may be involved in regulating inflammation in the middle
      ear by inactivating PAF, the potent proinflammatory autacoid.

PMID- 9519379
TI  - Middle ear imaging via the eustachian tube with a superfine fiberoptic
      videomicroendoscope.
AB  - The aim of this study was to systemically evaluate the visualization of the
      middle ear structures with a superfine fiberoptic videomicroendoscope introduced
      via the eustachian tube. With the permission of the Finnish Ministry of Health
      ten temporal bone blocks were dissected from lately succumbed patients. An
      Olympus AF-8 (0.8 mm outer diameter) angiofiberscope was used. The AF-8
      fiberoptic videomicroendoscope is a straightforward-looking endoscope with a 55
      degrees field of view. The endoscope tip was introduced through the eustachian
      tube into the middle ear and the middle ear structures were visualized and
      counted. Forty-three anatomical structures were listed and the results presented
      in a categorized table. Nineteen anatomical objects among 43 were never observed
      in any temporal bone block. The rest of the anatomical structures were visualized
      to varying degrees.

PMID- 9519380
TI  - Haemophilus influenzae and Streptococcus pyogenes group A challenge induce a Th1
      type of cytokine response in cells obtained from tonsillar hypertrophy and
      recurrent tonsillitis.
AB  - We have previously shown that tonsil tissue both from children with tonsillar
      hypertrophy and recurrent tonsillitis is colonized and invaded by Haemophilus
      influenzae and Streptococcus pyogenes group A. In order to evaluate if these
      bacteria are involved in the immunopathogenesis of these two conditions,
      tonsillar cells from both groups were stimulated in vitro with intact, heat
      inactivated H. influenzae or S. pyogenes A. The immunoreactivity was evaluated by
      assessing the induction of cytokine production (IL-1 alpha, IL-1 beta, TNF-alpha,
      IL-6, IL-8, IL-2, IFN-gamma, IL-4, TNF-beta and IL-10), which was detected at the
      single-cell level. All cytokines studied except IL-4 were induced in both groups
      after stimulation with H. influenzae or S. pyogenes A. The dominating cytokines
      were IL-1 beta, IFN-gamma and TNF-beta. No major differences in the cytokine
      pattern or number of cytokine-producing cells were noticed between the two
      patient cohorts after H. influenzae stimulation. Activation by S. pyogenes A
      bacteria gave rise to higher frequencies of IFN-gamma- and TNF-beta-synthesizing
      cells in the recurrent tonsillitis group. The incidence of CD4-, CD8-positive T
      cells and CD40-positive B cells was comparable between the two groups while the
      MAC-387-positive macrophages were significantly higher in the recurrent
      tonsillitis groups. In conclusion, a Th1 type of cytokine response was found in
      both groups following stimulation with H. influenzae or S. pyogenes A.

PMID- 9519382
TI  - Kaposi's sarcoma of the tonsil.
AB  - Two cases of Kaposi's sarcoma presenting as tonsilar masses in HIV-positive
      patients are described. At the time of examination neither patient had other
      manifestations of AIDS. Both patients also had concomitant cervical
      lymphadenopathy at the time of presentation, but the tonsillar masses were the
      dominant clinical findings. Biopsy of both tonsils revealed typical features of
      Kaposi's sarcoma. Both patients subsequently defaulted treatment and have been
      lost to follow-up.

PMID- 9519381
TI  - Laser bronchoscopy in palliative treatment of malignant obstructing endobronchial
      tumors.
AB  - This retrospective study investigates the experience of our ENT Department in the
      palliative treatment of obstructive malignant bronchial tumors with endoscopic
      laser surgery. 82 laser procedures on 39 patients were performed between January
      1988 and December 1993. In 25 cases, a carbon dioxide (CO2) laser and, in 14
      cases, a combined CO2-Nd:YAG laser were used. In 60 procedures, more than half of
      the tumor could be resected with laser. In 22 cases, minor improvement of the
      bronchial airway was achieved. Subjectively, most of the patients felt improved
      breathing after surgery and all were ready to undergo repeated treatment if it
      was offered. Two fatal complications occurred. We conclude that endoscopic laser
      surgery is a relatively safe treatment modality for palliation of a compromised
      airway and can offer a better life quality to selected patients, although it also
      involves the possibility of fatal complications.

PMID- 9519383
TI  - Treatment of an esophagorespiratory fistula by insertion of an esophageal
      Montgomery and tracheal dynamic stent after failure of conventional
      endoprosthesis.
AB  - Esophagorespiratory fistulae at the adult age can develop through malignant tumor
      growth, endoscopy, bougienage, laser therapy, or through a radiochemotherapy. We
      report a female patient with inoperable bronchial cancer, who developed a
      symptomatic esophagorespiratory fistula during radiochemotherapy with cisplatin.
      At first, conventional plastic tubes and then novel selfexpanding silicone-coated
      Gianturco-Song stents were used in an unsuccessful attempt to close the fistula.
      After the extraction of two Gianturco-Song stents, the insertion of a Montgomery
      Salivary bypass stent in the esophagus and a dynamic stent in the trachea
      resulted in a permanent occlusion of the fistula. This case demonstrates that
      Montgomery-Salivary bypass stents do not tend to migrate due to their
      characteristic shape and self-fixation, and that the novel self-expanding,
      silicone coated Gianturco-Song stents can be extracted with rigid endoscopy if
      necessary.

PMID- 9519384
TI  - Pathological features of healing of a ruptured human round window membrane.
AB  - Pathology of a round window membrane rupture was demonstrated in a human temporal
      bone from a case in which labyrinthotomy had been performed through the round
      window membrane. Proliferation of mesothelial cells was seen in the inner layer
      of the membrane, and it appeared to be reinforced from the inside by these
      reactive cells. The middle layer of the membrane was thickened by increased
      collagen and elastin. The pathologic changes which take place during healing of
      the ruptured round window membrane are discussed.

PMID- 9519385
TI  - Chondrosarcoma of the temporal bone and otosclerosis.
AB  - Chondrosarcoma constitutes 6% of all primary bone tumors and 11% of malignant
      primary bone tumors. Nevertheless, in a review of the tumor registry of the
      University of Michigan covering a period of 50 years, there were only 3 cases
      involving the temporal bone. A case of a woman with a chondrosarcoma of the
      temporal bone that was partially resected by means of an infratemporal approach
      at the skull base is presented. This patient had previously undergone surgical
      treatment for otosclerosis of the other ear. Several considerations regarding
      survival factors in this type of tumor are dealt with in terms of the
      histological features, therapeutic options and anatomic location. The possibility
      that this lesion may originate from the persistence of the cartilaginous
      inclusions that some authors consider to be involved in the origin of
      otosclerosis is discussed.

PMID- 9519386
TI  - Themes in diagnostic decision making.
AB  - The diagnosis of communication disorders is a complex clinical task that can have
      significant clinical, social, and economic consequences for the patient. This
      issue is about the conceptual process by which clinicians perform this important
      clinical task. Through the presentation of ten clinical cases, experienced
      clinicians illustrate a variety of diagnostic decision-making approaches that can
      be used to answer important clinical questions. In this initial article, the
      diagnostic themes that have emerged from these cases are summarized and four
      diagnostic strategies that can be used in making clinical diagnoses are
      discussed.

PMID- 9519387
TI  - Late talker or SLI?: the story of Jay X.
AB  - Distinguishing between children who will "catch up" after delays in early
      language development (late talkers), and children whose early delays are a
      harbinger of the condition known as specific language impairment (SLI), remains
      one of the biggest mysteries facing speech-language pathologists who work with
      young children. The case of Jay X, a preschool child with a history of delayed
      language acquisition, illustrates the process by which the crucial pieces of
      clinical information are accumulated and interpreted to make this determination.

PMID- 9519388
TI  - Solving the mystery of intermittent fluency breaks in a preschool child: chronic
      stuttering or normal fluency breaks?
AB  - The possibility of chronic stuttering is investigated in a preschool boy with a
      brief history of intermittent fluency breaks. The variability of the behavior
      adds to the mystery and makes the diagnosis of unusual or stuttering-like fluency
      breaks particularly difficult. Clues for solving this mystery are obtained from
      both the child and his parents. Verbal and nonverbal behaviors are considered,
      and the child's capacity for producing fluent speech is stressed during a formal
      evaluation to determine the effect of communicative demands. Detective work by
      the investigator takes the reader through a series of diagnostic decisions that
      eventually leads to cracking the case.

PMID- 9519389
TI  - Sudden onset of "stuttering" in an adult: neurogenic or psychogenic?
AB  - A 30-year-old woman hit her head during an automobile accident and was admitted
      to the hospital. One week later magnetic resonance imaging (MRI) showed a right
      frontal/parietal lesion. Among the behavioral sequelae were mild ataxia with
      trunkal instability and dysfluent speech accompanied by prominent shaking of the
      right leg, face and neck tension, and facial twitching. The speech-language
      pathologist thought the patient was not aphasic but rather was stuttering and
      treated her for about a month with pacing and "easy onset" techniques to which
      she showed fair response. The diagnostic question in this case is whether the
      stuttering was the result of the brain damage (neurogenic) or of the stressful
      events she had experienced (psychogenic). In this article we review her case and
      the process we used in arriving at an "expert" opinion.

PMID- 9519390
TI  - Do actions speak louder than words? The case of the disappearance of social
      communication oddities.
AB  - Within the last decade, researchers and clinicians have reported an increase in
      the incidence and diagnosis of Autism Spectrum Disorder (ASD). Various factors
      have been proposed for this apparent change including broader diagnostic
      criteria, greater public awareness, biological and environmental interactions,
      and earlier detection. However, it has been observed in a certain percentage of
      children, during the toddler and preschool years and before intervention is
      introduced, that severe language deficits distort social and self-regulatory
      behavior to such a degree that they mimic the characteristics of ASD.
      Professional caution is vital in this regard to describe early functioning and to
      defer diagnosis until the effects of intervention and treatment can be monitored
      over time. The case of Nicole, a preschooler with developmental delays and social
      communication oddities, illustrates what I believe is the most professionally
      responsible, cautious, family-centered, and data-based diagnostic process that
      links assessment, intervention, and evaluation for young children with early
      developmental difficulties.

PMID- 9519391
TI  - Aphasia or dementia: the cautionary tale of Dr. JJ.
AB  - This case study involves the differential diagnosis of aphasia versus dementia.
      However, the case of Dr. JJ is instructive from a number of aspects, presented
      here as "cautionary notes" which are intended to remind clinicians of sometimes
      forgotten interpersonal issues in the diagnosis of disorders of speech and
      language. This case also is intended to illustrate that merely distinguishing
      between dementia and aphasia is sometimes inadequate, particularly when
      potentially transmittable (and in some cases, curable) dementias might be
      involved.

PMID- 9519392
TI  - The case of the lawyer's lugubrious language: dysarthria plus primary progressive
      aphasia or dysarthria plus dementia?
AB  - A productive, intelligent, 60-year-old practicing attorney slowly begins to
      notice that the language that he has commanded throughout his life is beginning
      to become more difficult to produce, exacting its toll on his mental energy and
      emotional stability. His search for answers to his diminished "memory for words"
      leads him through the fetid ranks of traditional medicine and into the search for
      a differential diagnosis involving clinical neurology, neuropsychology, and
      speech-language pathology. Consistencies and conflicts in the signs and symptoms
      between the competing diagnoses raise theoretical and clinical classification
      issues. A course of treatment for aphasia provides evidence to support the
      diagnosis of primary progressive aphasia, but the development of concommitant
      spastic dysarthria and dysphagia challenge current wisdom about the underlying
      neuropathology of aphasia and support a diagnosis of early dementia. A selective
      but steady and rapid decline of abilities over the course of 2 years leads to the
      patient's death and autopsy, from which a neuropathologic analysis was to provide
      the "final" and "ultimate" diagnosis. But it doesn't!

PMID- 9519393
TI  - "Speech problem" subsequent to carbon monoxide exposure? I the jury.
AB  - Exposure to carbon monoxide can damage the nervous system. Sometimes that damage
      disrupts speech, and sometimes it does not. And, when it does, not all of what
      one hears may have an organic basis. Coming to grips with altered speech can
      alter people in different ways--consciously and unconsciously. Finding out what
      is real and what is not is a good reason for getting up in the morning. It's my
      job. I'm a speech pathologist.

PMID- 9519394
TI  - Acquired neurologic deficits in young children: a diagnostic journey with Dora.
AB  - Young children with limited communication abilities are often difficult to
      diagnose. When a neurologic insult occurs prior to language development, the
      communication effects tend to be less predictable than when the same event occurs
      in an older child or in an adult with a history of "normal" language use.
      Information in the medical chart regarding status during prelinguistic periods
      for cognition, motor, and verbal function should be helpful in predicting
      outcomes in some instances, but a series of decisions, over time, are likely to
      be necessary to reach a definitive communication diagnosis. As children become
      more verbal, the characteristics of the motor speech system can lead to new or
      changing diagnoses.

PMID- 9519395
TI  - Chronic cough: in search of the etiology.
AB  - Successful treatment of a voice problem requires an accurate diagnosis. The
      clinician often needs to piece the diagnosis together from previous treatments
      that failed, from an accurate and involved case history, and from examination of
      the larynx during speech and vegetative tasks. This case challenges the
      clinician's ability to question appropriately, to listen intently, and to observe
      critically before making the diagnosis. With the correct diagnosis, the patient
      found relief from her chronic cough.

PMID- 9519396
TI  - Stroke with dysarthria: evaluate and treat; garden variety or down the garden
      path?
AB  - The case of a man who initially presented to an emergency room with an isolated
      dysarthria is reviewed in order to demonstrate how the history, clinical context,
      and clinical observations can lead to accurate or inaccurate diagnosis. The
      diagnostic process in this case illustrates (1) the value of experience in
      clinical practice; (2) the role of the history and clinical context in diagnosis,
      but their occasional capacity to mislead; (3) the importance of distinguishing
      evidence from inference; (4) the use of deductive strategies and pattern
      recognition in speech diagnosis; (5) the importance of diagnostic vigilance; (6)
      the value of distinguishing among dysarthria types; and (7) the contribution that
      the diagnosis of speech disorders can make to the localization and diagnosis of
      neurologic disease.

PMID- 9519397
TI  - Gene therapy in sports medicine.
AB  - Sports injuries frequently involve tissues that have limited healing
      capabilities. In order to improve the healing process and thus prevent the
      serious consequences of injury, it is necessary to understand the molecular and
      cellular biology of healing. Several growth factors and other cytokines have been
      identified as important mediators of a successful healing process. Such molecules
      have promise as novel agents for the treatment of sporting injuries, but there is
      presently no clinically useful way to deliver them. Gene transfer may be used to
      serve this purpose. In this role, gene therapy functions as a type of local
      biological drug delivery system. Recent studies have shown the feasibility of
      transferring marker genes to synovium, chondrocytes, meniscal fibrochondrocytes,
      tenocytes and ligamental fibroblasts, prompting optimism about the eventual
      success of this approach.

PMID- 9519399
TI  - Anaerobic fitness testing of wheelchair users.
AB  - Anaerobic exercise testing has been applied since the 1970s as a procedure for
      estimating the capacity of local energy mechanisms dominating short term
      exercise. Compared with lower-body anaerobic testing, upper-body anaerobic
      testing is relatively new and less fully investigated. The reported data in this
      area are limited, and there is a paucity of reference values. For this review,
      the literature was searched by computerised inquiries of international and local
      databases, as well as personal access to PhD theses and congress proceedings.
      This article reviews the existing literature, covering a period of 20 years from
      1976 to 1995. Data are reported concerning the findings of variables relevant to
      the anaerobic capacity of wheelchair users. The research findings revealed in the
      literature published so far are analysed here with particular attention paid to
      the methods and instrumentation used (type of ergometer and protocol utilised in
      the tests). Limitations in existing instrumentation and research designs and
      goals for further study have been suggested. Specific sections analyse the
      relevance of anaerobic performance variables to the classification and activity
      level of the individuals involved and their relevance to daily life and sports
      related physical performance. Inter-relationships observed between anaerobic and
      aerobic capacity indices are discussed with respect to the limiting nature of
      local muscular fatigue over central processes. This information may be helpful in
      better understanding the exercise limitations and potential of wheelchair users
      with lower-limb impairments. Thus, clinical application of anaerobic fitness
      testing in these individuals may be enhanced.

PMID- 9519400
TI  - Elbow, forearm and wrist injuries in the athlete.
AB  - Competitive and recreational athletes sustain a wide variety of soft tissue,
      bone, ligament, tendon and nerve damage to their upper extremities. Most such
      injuries are related to direct trauma or repetitive stress, and account for a
      significant amount of 'down time' for athletes participating in a wide range of
      sports, particularly those in which the arm is utilised for throwing, catching or
      swinging. Overuse injuries to the elbow include musculotendinous injuries, ulnar
      nerve injuries and ligamentous injuries. Osteochondrol lesions of the capitellum
      and posterior impingement injuries in the joint are frequently seen in athletes
      as well. Acute traumatic injuries to the elbow include tendon ruptures, elbow
      dislocations and intra-articular fractures. Forearm overuse injuries in athletes
      include fracture of the carpal scaphold, fracture of the hook of the hamate,
      Kienbock's syndrome and pisoquetral syndromes. ligamentous injuries include
      scapholunate, lunotriquetral and midcarpal instability injuries. Injuries to the
      distal radio-ulnar joint and triangular fibrocartilage are also quite common in
      athletes, and require careful evaluation and treatment.

PMID- 9519402
TI  - Nonsurgical treatment for tennis elbow.

PMID- 9519401
TI  - Concussive convulsions. Incidence in sport and treatment recommendations.
AB  - Concussive convulsions (CC) are nonepileptic phenomena which are an immediate
      sequelae of concussive brain injury. Although uncommon, occurring with an
      approximate incidence of 1 case per 70 concussions, these episodes are often
      confused with post-traumatic epilepsy which may occur with more severe structural
      brain injury. The pathophysiological mechanism of CC remains speculative, but may
      involve a transient traumatic functional decerebration with loss of cortical
      inhibition and release of brainstem activity. The phenomenology of the CC is
      somewhat akin to convulsive syncope, with an initial tonic phase occurring within
      2 seconds of impact, followed by a clonic or myoclonic phase which may last
      several minutes. Lateralising features are common during the convulsions. There
      is no evidence of structural or permanent brain injury on clinical assessment,
      neuropsychological testing or neuroimaging studies. Long term outcome is
      universally good with no evidence of long term epilepsy and athletes are usually
      able to return to sport within 2 weeks. The correct management of these episodes
      centres on the appropriate management of the associated concussive injury and the
      exclusion of other cerebral injury by medical assessment. The CC requires no
      specific management beyond immediate onfield first aid measures such as
      protection of the airway. Antiepileptic therapy is not indicated and prolonged
      absence from sport is unwarranted. These episodes, although dramatic, are
      relatively straightforward to manage and all team physicians and those involved
      in athlete care need to be aware of this condition.

PMID- 9519398
TI  - Total Achilles tendon rupture. A review.
AB  - There are only a few epidemiological studies on the incidence of Achilles tendon
      (AT) ruptures. These show an increase in incidence in the West during the past
      few decades. The main reason is probably the increased popularity of recreational
      sports among middle-aged people. Ball games constitute the cause of over 60% of
      AT ruptures in many series. The 2 most frequently discussed pathophysiological
      theories involve chronic degeneration of the tendon and failure of the inhibitory
      mechanism of the musculotendinous unit. There are reports of AT ruptures related
      to the use of corticosteroids, either systemically or locally, but the role of
      corticosteroids in large patient series is marginal. In addition, recent studies
      do not confirm earlier findings of blood group O dominance in patients with AT
      rupture. Comparable series have been published with surgical versus nor surgical
      treatment and postoperative cast immobilisation versus early functional
      treatment. Although conservative treatment has its own supporters, surgical
      treatment seems to have been the method of choice in the late 1980s and the 1990s
      in athletes and young people and in cases of delayed ruptures. Early ruptures in
      non-athletes can also be treated conservatively. In small series of compliant,
      well motivated patients, functional postoperative treatment has been reported to
      be well tolerated, safe and effective. The lack of a universal, consistent
      protocol for subjective and objective evaluation of AT ruptures has prevented any
      direct comparison of the results. The results have been often assessed according
      to the criteria of Lindholm or Percy and Conochie, but no scoring is available
      for the analysis. We assessed a new scoring method and analysed the prognostic
      factors related to the results. There is also no single, uniformly accepted
      surgical technique. Although early ruptures have been treated successfully with
      simple end-to-end suture, many authors have combined simple tendon suture with
      plastic procedures of various types. No randomised study comparing simple suture
      technique and repair with augmentation could be found in the literature. The
      major complaint against surgical treatment has been the high rate of
      complications. Most are minor wound complications, which delay improvement but do
      not influence the final outcome. Major complications are rare, but often
      difficult to treat with minor procedures. For instance, large postoperative skin
      and soft tissue defects in the Achilles region can be treated successfully with a
      microvascular free flap reconstruction. The complications of conservative
      treatment include mostly reruptures and residual lengthening of the tendon, which
      may result in significant calf muscle weakness. It has been postulated that a
      physically inactive lifestyle leads to a decrease in tendon vascularisation,
      while maintenance of a continuous level of activity counteracts the structural
      changes within the musculotendinous unit induced by inactivity and aging. Proper
      warm-up and stretching are essential for preventing musculotendinous injuries,
      but improper or excessive stretching or warming-up can predispose to these
      injuries.

PMID- 9519404
TI  - Isoprenoid biosynthesis: manifold chemistry catalyzed by similar enzymes.
AB  - Isoprenoids comprise a family of more than 23,000 natural products, among them
      the precursors of cholesterol and taxol. The structures of three isoprenoid
      cyclizing enzymes have recently been determined and here are placed in the
      greater context of isoprenoid biosynthesis. On the basis of reaction mechanisms,
      a subdivision into class I and class II enzymes is proposed. The chain folds of
      these enzymes also appear to fall into the same two distinct classes, suggesting
      that class I and class II enzymes have evolved separately.

PMID- 9519403
TI  - Processivity of DNA polymerases: two mechanisms, one goal.
AB  - Replicative DNA polymerases are highly processive enzymes that polymerize
      thousands of nucleotides without dissociating from the DNA template. The recently
      determined structure of the Escherichia coli bacteriophage T7 DNA polymerase
      suggests a unique mechanism that underlies processivity, and this mechanism may
      generalize to other replicative polymerases.

PMID- 9519406
TI  - Crystal structure of p14TCL1, an oncogene product involved in T-cell
      prolymphocytic leukemia, reveals a novel beta-barrel topology.
AB  - BACKGROUND: Chromosome rearrangements are frequently involved in the generation
      of hematopoietic tumors. One type of T-cell leukemia, T-cell prolymphocytic
      leukemia, is consistently associated with chromosome rearrangements characterized
      by the juxtaposition of the TCRA locus on chromosome 14q11 and either the TCL1
      gene on 14q32.1 or the MTCP1 gene on Xq28. The TCL1 gene is preferentially
      expressed in cells of early lymphoid lineage; its product is a 14 kDa protein
      (p14TCL1), expressed in the cytoplasm. p14TCL1 has strong sequence similarity
      with one product of the MTCP1 gene, p13MTCP1 (41% identical and 61% similar). The
      functions of the TCL1 and MTCP1 genes are not known yet. They have no sequence
      similarity to any other published sequence, including those of well-documented
      oncogene families responsible for leukemia. In order to gain a more fundamental
      insight into the role of this particular class of oncogenes, we have determined
      the three-dimensional structure of p14TCL1. RESULTS: The crystal structure of
      p14TCL1 has been determined at 2.5 A resolution. The structure was solved by
      molecular replacement using the solution structure of p13MTCP1, revealing p14TCL1
      to be an all-beta protein consisting of an eight-stranded antiparallel beta
      barrel with a novel topology. The barrel consists of two four-stranded beta
      meander motifs, related by a twofold axis and connected by a long loop. This
      internal pseudo-twofold symmetry was not expected on basis of the sequence alone,
      but structure-based sequence analysis of the two motifs shows that they are
      related. The structures of p13MTCP1 and p14TCL1 are very similar, diverging only
      in regions that are either flexible and/or involved in crystal packing. p14TCL1
      forms a tight crystallographic dimer, probably corresponding to the 28 kDa
      species identified in solution by gel filtration experiments. CONCLUSIONS:
      Structural similarities between p14TCL1 and p13MTCP1 suggest that their (unknown)
      function may be analogous. This is confirmed by the fact that these proteins are
      implicated in analogous diseases. Their structure does not show similarity to
      other oncoproteins of known structure, confirming their classification as a novel
      class of oncoproteins.

PMID- 9519405
TI  - Structural analysis of the Spiroplasma virus, SpV4: implications for evolutionary
      variation to obtain host diversity among the Microviridae.
AB  - BACKGROUND: Spiroplasma virus, SpV4, is a small, non-enveloped virus that infects
      the helical mollicute Spiroplasma melliferum. SpV4 exhibits several similarities
      to the Chlamydia phage, Chp1, and the Coliphages alpha 3, phi K, G4 and phi X174.
      All of these viruses are members of the Microviridae. These viruses have
      isometric capsids with T = 1 icosahedral symmetry, cause lytic infections and are
      the only icosahedral phages that contain single-stranded circular DNA genomes.
      The aim of this comparative study on these phages was to understand the role of
      their capsid proteins during host receptor recognition. RESULTS: The three
      dimensional structure of SpV4 was determined to 27 A resolution from images of
      frozen-hydrated particles. Cryo-electron microscopy (cryo-EM) revealed 20,
      approximately 54 A long, 'mushroom-like' protrusions on the surface of the
      capsid. Each protrusion comprises a trimeric structure that extends radially
      along the threefold icosahedral axes of the capsid. A 71 amino acid portion of
      VP1 (the SpV4 capsid protein) was shown, by structural alignment with the atomic
      structure of the F capsid protein of phi X174, to represent an insertion sequence
      between the E and F strands of the eight-stranded antiparallel beta-barrel.
      Secondary structure prediction of this insertion sequence provided the basis for
      a probable structural motif, consisting of a six-stranded antiparallel beta sheet
      connected by small turns. Three such motifs form the rigid stable trimeric
      structures (mushroom-like protrusions) at the threefold axes, with hydrophobic
      depressions at their distal surface. CONCLUSIONS: Sequence alignment and
      structural analysis indicate that distinct genera of the Microviridae might have
      evolved from a common primordial ancestor, with capsid surface variations, such
      as the SpV4 protrusions, resulting from gene fusion events that have enabled
      diverse host ranges. The hydrophobic nature of the cavity at the distal surface
      of the SpV4 protrusions suggests that this region may function as the receptor
      recognition site during host infection.

PMID- 9519407
TI  - The structure of tobacco ringspot virus: a link in the evolution of icosahedral
      capsids in the picornavirus superfamily.
AB  - BACKGROUND: Tobacco ringspot virus (TRSV) is a member of the nepovirus genus of
      icosahedral RNA plant viruses that cause disease in fruit crops. Nepoviruses,
      comoviruses and picornaviruses are classified in the picornavirus superfamily.
      Crystal structures of comoviruses and picornaviruses and the molecular mass of
      the TRSV subunit (sufficient to accommodate three beta-barrel domains) suggested
      that nepoviruses may represent a link in the evolution of the picornavirus
      capsids from a T = 3 icosahedral virus. This evolutionary process is thought to
      involve triplication of the capsid protein gene, to encode a three-domain
      polyprotein, followed by development of cleavage sites in the interdomain linking
      regions. Structural studies on TRSV were initiated to determine if the TRSV
      subunit corresponds to the proposed uncleaved three-domain polyprotein. RESULTS:
      The 3.5 A resolution structure of TRSV shows that the capsid protein consists of
      three beta-barrel domains covalently linked by extended polypeptides. The order
      of connectivity of the domains in TRSV confirms the proposed connectivity for the
      precleaved comovirus and picornavirus capsid polyprotein. Structural differences
      between equivalent domains in TRSV and comoviruses are confined to the external
      surface loops, interdomain connecting polypeptides and N termini. The three
      different domains within TRSV and comoviruses are more closely related at the
      structural level than the three individual domains within picornaviruses.
      CONCLUSIONS: The structural results confirm the notion of divergent evolution of
      the capsid polyproteins of nepoviruses, comoviruses and picornaviruses from a
      common ancestor. A number of residues were found to be conserved among various
      nepoviruses, some of which stabilize the quaternary structure of the three
      domains in the TRSV capsid protein subunit. Two conserved regions were identified
      on the external surface of TRSV, however, mutational studies will be needed to
      understand their functional significance. Nepoviruses transmitted by the same
      nematode species do not share regions with similar amino acid composition on the
      viral surface.

PMID- 9519408
TI  - The 3-D structure of a folate-dependent dehydrogenase/cyclohydrolase bifunctional
      enzyme at 1.5 A resolution.
AB  - BACKGROUND: The interconversion of two major folate one-carbon donors occurs
      through the sequential activities of NAD(P)-dependent methylene[H4]folate
      dehydrogenase (D) and methenyl[H4]folate cyclohydrolase (C). These activities
      often coexist as part of a multifunctional enzyme and there are several lines of
      evidence suggesting that their substrates bind at overlapping sites. Little is
      known, however, about the nature of this site or the identity of the active-site
      residues for this enzyme family. RESULTS: We have determined, to 1.5 A
      resolution, the structure of a dimer of the D/C domain of the human trifunctional
      cytosolic enzyme with bound NADP cofactor, using the MAD technique. The D/C
      subunit is composed of two alpha/beta domains that assemble to form a wide cleft.
      The cleft walls are lined with highly conserved residues and NADP is bound along
      one wall. The NADP-binding domain has a Rossmann fold, characterized by a
      modified diphosphate-binding loop fingerprint-GXSXXXG. Dimerization occurs by
      antiparallel interaction of two NADP-binding domains. Superposition of the two
      subunits indicates domain motion occurs about a well-defined hinge region.
      CONCLUSIONS: Analysis of the structure suggests strongly that folate-binding
      sites for both activities are within the cleft, providing direct support for the
      proposed overlapping site model. The orientation of the nicotinamide ring
      suggests that in the dehydrogenase-catalyzed reaction hydride transfer occurs to
      the pro-R side of the ring. The identity of the cyclohydrolase active site is not
      obvious. We propose that a conserved motif-Tyr52-X-X-X-Lys56- and/or a Ser49
      Gln100-Pro102 triplet have a role in this activity.

PMID- 9519409
TI  - Structure of Escherichia coli ribokinase in complex with ribose and dinucleotide
      determined to 1.8 A resolution: insights into a new family of kinase structures.
AB  - BACKGROUND: D-ribose must be phosphorylated at O5' before it can be used in
      either anabolism or catabolism. This reaction is catalysed by ribokinase and
      requires the presence of ATP and magnesium. Ribokinase is a member of a family of
      carbohydrate kinases of previously unknown structure. RESULTS: The crystal
      structure of ribokinase from Escherichia coli in complex with ribose and
      dinucleotide was determined at 1.84 A resolution by multiple isomorphous
      replacement. There is one 33 kDa monomer of ribokinase in the asymmetric unit but
      the protein forms a dimer around a crystallographic twofold axis. Each subunit
      consists of a central alpha/beta unit, with a new type of nucleotide-binding
      fold, and a distinct beta sheet that forms a lid over the ribose-binding site.
      Contact between subunits involves orthogonal packing of beta sheets, in a novel
      dimer interaction that we call a beta clasp. CONCLUSIONS: Inspection of the
      complex indicates that ribokinase utilises both a catalytic base for activation
      of the ribose in nucleophilic attack and an anion hole that stabilises the
      transition state during phosphoryl transfer. The structure suggests an ordered
      reaction mechanism, similar to those proposed for other carbohydrate kinases that
      probably involves conformational changes. We propose that the beta-clasp
      structure acts as a lid, closing and opening upon binding and release of ribose.
      From these observations, an understanding of the structure and catalytic
      mechanism of related sugar kinases can be obtained.

PMID- 9519410
TI  - The allosteric regulation of pyruvate kinase by fructose-1,6-bisphosphate.
AB  - BACKGROUND: Yeast pyruvate kinase (PK) catalyzes the final step in glycolysis.
      The enzyme therefore represents an important control point and is allosterically
      activated by fructose-1,6-bisphosphate (FBP). In mammals the enzyme is found as
      four different isozymes with different regulatory properties: two of these
      isozymes are produced by alternate splicing. The allosteric regulation of PK is
      directly related to proliferation of certain cell types, as demonstrated by the
      expression of an allosterically regulated isozyme in tumor cells. A model for the
      allosteric transition from the inactive (T) state to the active (R) state has
      been proposed previously, but until now the FBP-binding site had not been
      identified. RESULTS: We report here the structures of PK from yeast complexed
      with a substrate analog and catalytic metal ions in the presence and absence of
      bound FBP. The allosteric site is located 40 A from the active site and is
      entirely located in the enzyme regulatory (C) domain. A phosphate-binding site
      for the allosteric activator is created by residues encoded by a region of the
      gene corresponding to the alternately spliced exon of mammalian isozymes. FBP
      activation appears to induce several conformational changes among active-site
      sidechains through a mechanism that is most likely to involve significant domain
      motions, as previously hypothesized. CONCLUSIONS: The structure and location of
      the allosteric activator site agrees with the pattern of alternate genetic
      splicing of the PK gene in multicellular eukaryotes that distinguishes between a
      non-regulated isozyme and the regulated fetal isozymes. The conformational
      differences observed between the active sites of inactive and fully active PK
      enzymes is in agreement with the recently determined thermodynamic mechanism of
      allosteric activation through a 'metal relay' that increases the affinity of the
      enzyme for its natural phosphoenolpyruvate substrate.

PMID- 9519411
TI  - A novel calcium-sensitive switch revealed by the structure of human S100B in the
      calcium-bound form.
AB  - BACKGROUND: S100B is a homodimeric member of the EF-hand calcium-binding protein
      superfamily. The protein has been implicated in cellular processes such as cell
      differentiation and growth, plays a role in cytoskeletal structure and function,
      and may have a role in neuropathological diseases, such as Alzheimers. The
      effects of S100B are mediated via its interaction with target proteins. While
      several studies have suggested that this interaction is propagated through a
      calcium-induced conformational change, leading to the exposure of a hydrophobic
      region of S100B, the molecular details behind this structural alteration remain
      unclear. RESULTS: The solution structure of calcium-saturated human S100B (Ca(2+)
      S100B) has been determined by heteronuclear NMR spectroscopy. Ca(2+)-S100B forms
      a well defined globular structure comprising four EF-hand calcium-binding sites
      and an extensive hydrophobic dimer interface. A comparison of Ca(2+)-S100B with
      apo S100B and Ca(2+)-calbindin D9k indicates that while calcium-binding to S100B
      results in little change in the site I EF-hand, it induces a backbone
      reorientation of the N terminus of the site II EF-hand. This reorientation leads
      to a dramatic change in the position of helix III relative to the other helices.
      CONCLUSIONS: The calcium-induced reorientation of calcium-binding site II results
      in the increased exposure of several hydrophobic residues in helix IV and the
      linker region. While following the general mechanism of calcium modulatory
      proteins, whereby a hydrophobic target site is exposed, the 'calcium switch'
      observed in S100B appears to be unique from that of other EF-hand proteins and
      may provide insights into target specificity among calcium modulatory proteins.

PMID- 9519413
TI  - A novel mode of target recognition suggested by the 2.0 A structure of holo S100B
      from bovine brain.
AB  - BACKGROUND: S100B, a small acidic calcium-binding protein, is a member of the
      S100 protein family and is a multifunctional protein capable of binding several
      target molecules, such as cytoskeletal proteins and protein kinases, in a calcium
      dependent manner. S100B is a homodimer of S100 beta subunits (beta beta) with a
      total of four calcium-binding motifs called EF hands. S100B is found abundantly
      in nervous tissue and has been implicated in Alzheimer's disease and Down's
      syndrome. Structural analysis of S100B in the calcium-bound state is required to
      gain a better understanding of the conformational changes that occur to S100B
      upon calcium binding and to elucidate the mode of recognition between S100B and
      its target molecules. RESULTS: We have determined the three-dimensional structure
      of holo S100B from bovine brain at 2.0 A resolution by X-ray diffraction. The
      dimeric S100B molecule is formed by non-covalent interactions between large
      hydrophobic surfaces on both S100 beta subunits. There are two EF-hand motifs per
      S100 beta subunit, each of which binds one calcium ion. We observe, in the
      calcium-bound structure, dramatic changes in the conformation of the terminal
      helices, from the compact structure in the apo form to a more extended form upon
      binding calcium. Following these changes, an exposed hydrophobic core, surrounded
      by many negatively charged residues, is revealed. Cys84 is positioned at an
      exposed surface of S100B, surrounded by hydrophobic residues, and could form a
      disulfide bond to tau protein, one of the known target molecules thought to
      interact with S100B in this way. CONCLUSIONS: The molecular structure of holo
      S100B suggests a novel mode of target recognition for the S100 family of calcium
      binding proteins. Upon calcium binding, dramatic changes occur in the terminal
      helices of S100B, revealing a large hydrophobic surface, not observed in the apo
      form. It is through hydrophobic interactions and possibly a Cys84-mediated
      disulfide bond that S100B is thought to bind its target molecules.

PMID- 9519412
TI  - The three-dimensional structure of Ca(2+)-bound calcyclin: implications for
      Ca(2+)-signal transduction by S100 proteins.
AB  - BACKGROUND: Calcyclin is a member of the S100 subfamily of EF-hand Ca(2+)-binding
      proteins. This protein has implied roles in the regulation of cell growth and
      division, exhibits deregulated expression in association with cell
      transformation, and is found in high abundance in certain breast cancer cell
      lines. The novel homodimeric structural motif first identified for apo calcyclin
      raised the possibility that S100 proteins recognize their targets in a manner
      that is distinctly different from that of the prototypical EF-hand Ca2+ sensor,
      calmodulin. The NMR solution structure of Ca(2+)-bound calcyclin has been
      determined in order to identify Ca(2+)-induced structural changes and to obtain
      insights into the mechanism of Ca(2+)-triggered target protein recognition.
      RESULTS: The three-dimensional structure of Ca(2+)-bound calcyclin was calculated
      with 1372 experimental constraints, and is represented by an ensemble of 20
      structures that have a backbone root mean square deviation of 1.9 A for the eight
      helices. Ca(2+)-bound calcyclin has the same symmetric homodimeric fold as
      observed for the apo protein. The helical packing within the globular domains and
      the subunit interface also change little upon Ca2+ binding. A distinct homology
      was found between the Ca(2+)-bound states of the calcyclin subunit and the
      monomeric S100 protein calbindin D9k. CONCLUSIONS: Only very modest Ca(2+)
      induced changes are observed in the structure of calcyclin, in sharp contrast to
      the domain-opening that occurs in calmodulin and related Ca(2+)-sensor proteins.
      Thus, calcyclin, and by inference other members of the S100 family, must have a
      different mode for transducing Ca2+ signals and recognizing target proteins. This
      proposal raises significant questions concerning the purported roles of S100
      proteins as Ca2+ sensors.

PMID- 9519414
TI  - History of urinary diversion.
AB  - In 1852, Simon was the first to describe a urinary diversion using intestinal
      segments. In the late 19th and early 20th century, in the absence of antibiotics,
      urinary diversion using bowel segments carried a high risk of peritonitis. When
      Coffey introduced a new method for ureteric implantation in 1911,
      ureterosigmoidostomy became the most frequently used technique. The ileal
      conduit, first described by Zaayer in 1911, was established as a standard
      technique by Bricker in 1950. At the same time, Ferris and Oedel demonstrated a
      hyperchloremic metabolic acidosis in 80% of the patients with
      ureterosigmoidostomy, and the ileal conduit became the preferred from of urinary
      diversion. The first attempts to create a continent urinary diversion were
      undertaken by Tizzoni and Foggi in 1888. Mauclaire, in 1895, used the isolatec
      rectum as a urinary reservoir. Two findings were essential for the development of
      modern continent urinary diversion: Kock established the principle of bowel
      detubularization to create a low-pressure reservoir, and Lapides popularized the
      use of clean intermittent catheterization. Utilizing these techniques, a variety
      of continent reservoirs were introduced. The majority of these used either ileal
      segments, like the Hautmann neobladder, or ileocecal segments, like 'Le Bag'.
      Sinaiko was the first to use the stomach for the creation of a urinary reservoir
      in 1956. Continent urinary diversion is the method of choice in a large number of
      patients today. Experimental work demonstrated that the creation of a new bladder
      using cultured urothelial and muscle cells with biodegradable polymers as a
      scaffold is feasible, and future developments may be vastly influenced by these
      techniques.

PMID- 9519415
TI  - Normal ranges of renal physiological parameters for technetium-99m
      mercaptoacetyltriglycine and the influence of age and sex using a camera-based
      method.
AB  - 162 normal Chinese men and women underwent a 99mTc MAG3 renal study. Seventy-two
      males and 90 females were evaluated in 5 age groups: group 1, 61-80 years; group
      2, 51-60 years; group 3, 41-50 years; group 4, 31-40 years, and group 5, 21-30
      years. Each subject was required to fit the following criteria: (1) clinically no
      history of renal, urinary disorders and systemic diseases, normal blood pressure,
      kidney morphology, urinary examination and serum creatinine, and (2) for the
      gamma camera study normal hydration and renal images, and no pelvic, ureteric
      dilatation or retention of tracer should be found. The normal range of common
      physiological parameters for 99mTc MAG3 renal studies was measured in normal
      subjects. The effective renal plasma flow (ERPF, camera-based Schlegel method),
      percent function in each kidney (renal index, RI), time of peak renal parenchymal
      activity (Tmax) and half time of parenchymal activity following the peak (T1/2)
      were evaluated. The Tmax and T1/2 were determined with regions of interest over
      the entire kidney. The results showed that (1) between the sexes, there were no
      significant differences for any parameter; (2) between the age groups, the only
      significant difference was a decrease in ERPF, normalized for body surface area,
      with increasing age (group 1, 511.3 +/- 91.2; group 2, 559.5 +/- 102.1; group 3,
      577.1 +/- 79.2; group 4, 607.8 +/- 101.1, and group 5, 610.2 +/- 109.2), and (3)
      the RI, Tmax and T1/2 were symmetrical and did not vary between the sexes or age
      groups (left vs. right: RI = 49.6 +/- 2.2 vs. 50.4 +/- 2.2%, Tmax = 3.63 +/- 1.13
      vs. 3.75 +/- 1.11 min, and T1/2 = 5.38 +/- 1.65 vs. 5.83 +/- 1.88 min). We find
      that (1) ERPF for 99mTc MAG3 decreases with age in normal Chinese, which is
      similar to the results of Western countries, and (2) the RI, Tmax and T1/2 were
      symmetrical and did not vary between the sexes or age groups in normal Chinese,
      and are also similar to the results of Western countries.

PMID- 9519416
TI  - Microvascular invasion in prostate cancer: prognostic significance in patients
      treated by radical prostatectomy for clinically localized carcinoma.
AB  - OBJECTIVE: To investigate the clinical significance of vascular invasion in
      prostate cancer patients treated by radical prostatectomy for clinically
      localized and locally advanced disease. MATERIALS AND METHODS: Vascular invasion
      was determined during a routine work-up of radical prostatectomy specimens of 273
      patients who underwent surgery for prostatic carcinoma. The correlation with
      other pathological variables was investigated. The prognostic influence for
      clinical progression, local recurrence, distant metastases, biochemical
      progression, overall survival and cancer-specific survival was determined.
      RESULTS: Vascular invasion was present in 33 patients (12%). Vascular invasion
      correlated significantly with capsular perforation, seminal vesicle invasion,
      positive margins of resection, perineural invasion, high grade, and pathological
      stage. Vascular invasion was a significant prognostic factor for clinical
      progression (p < 0.001), local recurrence (p = 0.007), distant metastases (p <
      0.001), biochemical progression (p < 0.001), overall survival (p = 0.02), and
      cancer-specific survival (p < 0.001). Multivariate analysis, adjusting for
      capsular perforation, high grade, and positive margins of resection, showed that
      vascular invasion was associated with a 2.5-fold increased risk for clinical
      progression. This relative risk was 2.3 for biochemical progression, and 2.7 for
      cancer-specific survival. CONCLUSION: Vascular invasion is a very important
      pathological variable for progression and survival, and must be evaluated on a
      routine basis during the work-up of radical prostatectomy specimens.

PMID- 9519417
TI  - Diagnostic significance of prostate-specific antigen velocity at intermediate PSA
      serum levels in relation to the standard deviation of different test systems.
AB  - Serial prostate-specific antigen (PSA) measurements (PSA velocity) as an
      additional instrument to detect prostatic cancer was introduced in 1992. It has
      previously been reported that PSA increase per year differed in the last 5 years
      prior to diagnosis in patients with benign prostatic hyperplasia (0.18
      ng/ml/year), locally confined (0.75 ng/ml/year) and metastasized (4.4 ng/ml/year)
      cancer of the prostate (CaP) in contrast to healthy men (0.04 ng/ml/year). The
      ability of PSA velocity to detect organ-confined CaP in patients with
      intermediate PSA serum values depends therefore on a reliable and reproducible
      PSA result. The present study comprised 85 men with PSA values between 3 and 8
      ng/ml (Abbott IMx). PSA measurements were repeated with Abbott IMx (n = 85
      patients) and Hybritech Tandem-E (n = 59 patients) assays. The PSA serum values
      differed from one examination to the other from 0.02 to 2.74 ng/ml with the
      Abbott IMx. Standard deviation amounted to 0.35 ng/ml with the Abbott IMx PSA
      assay. Using the Hybritech Tandem-E assay, mean standard deviation was 1.15 ng/ml
      and therefore higher than with the Abbott IMx assay. The difference from one test
      to the other ranged from 0.05 to 4.05 ng/ml with the Hybritech Tandem-E. Using
      the Abbott IMx assay, 10.6% of all repeat measurements exceeded 1 ng/ml whereas
      in the Hybritech Tandem-E assay 62.7% of the second measurements differed > 1
      ng/ml from the first PSA result. An increase in PSA serum values may therefore be
      due to intratest variation, physiological day-to-day variation as well as
      prostatic disease. It is important to notice that the intra-assay variation may
      be greater than the PSA increase per year in a patient with CaP. Therefore, PSA
      velocity seems to be of limited value.

PMID- 9519418
TI  - Response of prostate-specific antigen after androgen withdrawal and prognosis in
      men with metastatic prostate cancer.
AB  - OBJECTIVE: Patients with prostate cancer generally respond to androgen withdrawal
      therapy, but progression to androgen independence is frequently observed. To
      evaluate prognostic factors in metastatic prostate cancer, patients who had been
      treated with endocrine therapy were investigated. METHODS: One hundred and thirty
      nine patients with untreated metastatic prostate cancer (TxNxM1) who received
      endocrine therapy between 1986 and 1993 were included in the present study. Blood
      chemistry, histological grade, extent of bony metastases, clinical response to
      hormone therapy, and the prognosis of the patients were evaluated. RESULTS: With
      univariate analysis, performance status, hemoglobin concentration, serum alkaline
      phosphatase, lactate dehydrogenase, histological grade, extent of bony disease,
      and response of prostate-specific antigen (PSA) at 3 months were shown to be
      significant prognostic factors. With multivariate analyses, response of PSA and
      histological grade were significant factors predicting prognosis. CONCLUSIONS:
      Patients whose PSA had not normalized 3 months after the start of endocrine
      therapy were in the high-risk group, and should be given more aggressive
      treatment.

PMID- 9519419
TI  - An evaluation of pharmacokinetics and pharmacodynamics of leuprorelin acetate 3M
      depot in patients with advanced and metastatic carcinoma of the prostate.
AB  - OBJECTIVES: The investigational objectives of this open, noncomparative phase I
      study were to determine the pharmacokinetic profile of a single dose of 11.25 mg
      leuprorelin acetate, the effective duration of the chemical castration (serum
      testosterone < or = 1.73 nmol/l) and safety in patients with locally advanced
      and/or metastatic carcinoma of the prostate foreseen for chemical castration, in
      the hope that such a dose of leuprorelin acetate may be suitable as a depot
      formulation to be administered 3-monthly to these patients. METHODS: A total of
      24 males up to 85 years old with histologically proven advanced carcinoma of the
      prostate were enrolled in the study to obtain 18 eligible patients. Each patient
      was given 11.25 mg of leuprorelin acetate in a depot formulation subcutaneously
      after reconstitution in 2 ml of a special suspension vehicle. The study period
      lasted 24 weeks. Patients whose serum testosterone levels reincreased prior to
      the end of the observation period of 24 weeks were withdrawn from the study and
      received the monthly depot formulation of 3.75 mg of leuprorelin acetate.
      RESULTS: The 3M-depot formulation of leuprorelin acetate ensured continuous and
      constant drug release and effective suppression of testosterone serum levels to
      castration range for at least 13 weeks. After an initial rise, 5 alpha
      dihydrotestosterone as well as the gonadotropin serum levels of luteinizing
      hormone and follicular stimulating hormone reflected the testosterone serum
      pattern. CONCLUSION: The results of this study show that the 3M-depot preparation
      of leuprorelin acetate is effective in suppressing the serum testosterone levels
      to the castration range for a targeted period of at least 13 weeks.

PMID- 9519420
TI  - Study of calcium oxalate crystalluria on renal and vesical urines in stone
      formers and normal subjects.
AB  - OBJECTIVE: The aim of this study is to compare vesical and renal calcium oxalate
      crystalluria in an attempt to correlate crystal formation with chemical
      composition and calcium oxalate saturation of renal urine. MATERIAL AND METHODS:
      Urine specimens were directly collected from the bladder and the kidney, of 11
      stone formers and 11 control subjects under general anesthesia. The type of
      crystals present in urine as well as their size, number by cubic millimeter and
      state of aggregation were determined. In addition, calcium, magnesium, sodium,
      chloride, phosphate, citrate, oxalate, pyrophosphate and uric acid were measured
      in order to evaluate the calcium saturation status (EQUIL V program). RESULTS:
      Calcium oxalate crystals were detected in 3 stone formers (27%) and 2 control
      subjects (18%) in vesical urine and in 4 stone formers (36%) and 3 control
      subjects (27%) in renal urine. Only 2 stone formers presented with simultaneous
      renal and vesical crystalluria. Subjects of the two groups with and without renal
      crystalluria were compared in terms of chemical composition and calcium oxalate
      saturation of renal urine. Crystalluric subjects (n = 7) had significantly higher
      uricosuria (p = 0.02), calciuria (p = 0.04), magnesiuria (p = 0.04) and calcium
      oxalate molar product (p = 0.05) than noncrystalluric (n = 15); calcium oxalate
      saturation was similar (p = 0.5). CONCLUSIONS: Beyond theorical considerations on
      lithogenesis, our observations and in particular the apparent discrepancy between
      renal and vesical crystalluria pose the problem of the clinical interest of the
      evaluation of calcium oxalate crystalluria based on freshly voided urine in the
      assessing the lithogenic risk or in the follow-up of patients who are
      particularly prone to stone recurrence.

PMID- 9519421
TI  - Development of a turbidimetric assay to study the effect of urinary components on
      calcium oxalate precipitation.
AB  - The pharmacological treatment of calcium urinary stones, most of which are made
      of calcium oxalate (CaOx), is only prophylactic. The causes of nephrolithiasis
      are often unclear, and a number of patients were found to be deficient in
      physiological inhibitors, e.g. citrate, pyrophosphate, magnesium, and specific
      proteins. The identification and characterization of these inhibitors can be
      performed in vitro by a number of methods, most of which are complex and time
      consuming. Thus, we developed a simple turbidimetric method based on the
      precipitation of CaOx from a supersaturated solution. Using this approach, we
      determined that ionic strengths > 0.2 and pH < 5 inhibited the precipitation of
      CaOx. The first observation is of interest if one considers that the osmolarity
      of urine varies in the range of 50-1,400 mmol/kg, while the effect of pH is not
      usually seen in vivo because of the influence of other phenomena, such as the
      precipitation of uric acid. The activity of sodium chloride, magnesium and
      citrate was displayed at concentrations not far from their normal urinary level.
      Among several mono-, di- and tricarboxylic acids, like acetic, ascorbic, citric,
      isocitric, formic, fumaric, gluconic, glutaric, alpha-ketoglutaric, maleic,
      malic, malonic, propionic, pyruvic, succinic, and tartaric acid, only isocitric
      acid was more potent than citric acid. Pyrophosphate was a potent inhibitor in
      vitro, but its urinary level may not be sufficient for a significant effect in
      vivo. Amino acids like Ala, Arg, Asp, Glu, Gly, and Ser which are known to bind
      calcium, showed little activity. Work is in progress to search for new compounds
      potentially useful in the treatment of nephrolithiasis.

PMID- 9519422
TI  - Transurethral ureterolithotomy in 100 lower ureteral stones.
AB  - A total of 100 patients with lower ureter stones received transurethral
      ureterolithotripsy (TUL) using a pulsed dye laser and/or a pneumatic
      lithotriptor. Extracorporeal shock wave lithotripsy treatment was added in 15
      patients because fragments larger than 4 mm had been pushed back to the renal
      pelvis. The median stone size was 8 mm (range 3-22 mm). Operative time ranged
      between 3 and 157 min with a median of 30 min. Stone size correlated well with
      impaction, when impaction was defined as the inability of a guidewire to pass
      over the stone. Complete removal was defined as total clearance at 1 month
      without retreatment. The overall stone-free rate was 93%. Among the 7 not-stone
      free cases, 5 cases were considered to have been treated successfully because
      asymptomatic residual fragments were smaller than 4 mm, 1 case required
      retreatment to become stone free, and 1 case with a silent residual fragment of 8
      mm had been followed up for 3 months. The success rate was 98% when successful
      treatment was defined as total clearance or the presence of asymptomatic residual
      fragments of 4 mm or less without retreatment. Impaction was not a significant
      determining factor of stone-free rate (95.7 and 86.7%, respectively, p > 0.05)
      and in situ stone-free rate (TUL alone; 85.7 and 76.7%, respectively, p > 0.05).
      Two minor ureteral perforations were encountered. No patient required
      percutaneous nephrostomy or open surgery, or showed any late complications. TUL
      is a safe and successful method in managing lower ureteral stones.

PMID- 9519423
TI  - Obstructive jaundice: a unique presentation of primary obstructive megaureter.
AB  - A case of giant hydronephrosis leading to obstructive jaundice due to primary
      obstructive megaureter in an adult is the subject of this presentation. Giant
      hydronephrosis due to primary obstructive megaureter in adults is uncommon. This
      is also the first case of obstructive jaundice due to primary obstructive
      megaureter reported in the literature. The patient was initially treated with a
      percutaneous nephrostomy till the jaundice resolved. This was followed by
      definitive surgery in the form of ureteral tailoring and reimplantation along
      with nephroplication and nephropexy, with a successful outcome.

PMID- 9519424
TI  - Ovarian cystoid causing Kock pouch incontinence.
AB  - The Kock pouch is a well-known standard technique for continent urinary
      diversion. If incontinence occurs, it is mostly related to insufficiency of the
      efferent nipple valve. We present the rare case of a young woman with a Kock
      pouch suffering from urine loss caused by a large cystoid in the left ovary
      leading to compression of the pouch and destabilization of the nipple.

PMID- 9519425
TI  - Percutaneous endoscopic marsupialization of a pyelocaliceal diverticulum with
      milk of calcium stones.
AB  - Numerous reports have described the management of pyelocaliceal diverticula
      associated with milk of calcium renal stones. Traditionally, open surgical
      techniques to manage such diverticula have included marsupialization and
      fulguration of the diverticulum, or partial/total nephrectomy. Recently, however,
      these invasive procedures have been replaced by percutaneous techniques. We
      report a patient with spontaneous rupture of a pyelocaliceal diverticulum with
      milk of calcium renal stones, who was successfully treated with endourological
      procedures.

PMID- 9519426
TI  - Simultaneously occurring abdominal aortic aneurysm and invasive transitional cell
      carcinoma of the bladder and their synchronous management.
AB  - We report the case of a 70-year-old man who presented with an abdominal aortic
      aneurysm and invasive transitional cell carcinoma of the bladder. Synchronous
      surgical treatment was deemed necessary because of the iliac extension of the
      aneurysm. Radical cystectomy preceded the repair of the abdominal aortoiliac
      aneurysm and the bilateral cutaneous ureterostomy.

PMID- 9519427
TI  - Implications of BSE policy for livestock production and veterinary services in
      the United Kingdom.
AB  - The likely impacts of BSE policy on UK milk and beef markets and on livestock
      numbers between 1997 and 2000 are explored using a dynamic spreadsheet model of
      UK milk and beef production, and linked demand, price and supply models for
      alternative meats. Two accelerated slaughter policies are considered--one
      representing the 'Florence Agreement' and the other involving an additional
      culling of calves born to confirmed BSE cases. The projections show significant
      changes to livestock populations over the next few years with implications for
      veterinary inputs. It is estimated that the BSE crisis will result in a fall in
      expenditure on veterinary medicines and services of around 10 Pounds million in
      1999 (for the Florence Agreement) compared with that projected in the absence of
      the BSE crisis.

PMID- 9519429
TI  - South American camelids in the United Kingdom: population statistics, mortality
      rates and causes of death.
AB  - A survey of the health of South American camelids in the United Kingdom was
      carried out between December 1992 and June 1993; 123 members of the British
      Camelid Owners and Breeders Association and 19 non-members were sent
      questionnaires and usable responses were received from 84 (59 per cent). In total
      689 camelids were included, and in 1992, 66 per cent were Ilama, 21 per cent
      alpaca and 13 per cent guanaco. Their ages ranged from less than six months to
      over 10 years, with animals aged two to five years constituting the largest
      proportion. The mortality rates between 1990 and 1992 were 2.7 to 3.3 per cent
      for Ilama, 3.5 to 6.9 per cent for alpaca and 0 to 11.4 per cent for guanaco. The
      highest mortality was in animals less than six months and more than 10 years old;
      4 to 11 per cent of Ilama deaths and 17 to 33 per cent of alpaca deaths were in
      animals aged less than six months and a high proportion of these occurred during
      the first week of life. In the cases for which a cause was reported, accidents
      and injury accounted for 20 per cent of Ilama deaths, and perinatal deaths
      accounted for 22 per cent of alpaca deaths. A third of the deaths were reported
      as being of unknown cause, and a veterinary diagnosis was reported in less than
      half of the cases. These data suggest that attention to the environment and
      housing conditions of Ilama, the neonatal care of alpaca and improvements in
      diagnosis are priorities for reducing the mortality and improving the health of
      South American camelids in the UK.

PMID- 9519428
TI  - Femoral neck metaphyseal osteopathy in the cat.
AB  - This paper describes 17 cats that developed an idiopathic necrosis of the femoral
      neck. In four cats the lesions were bilateral when they were first examined and
      five cats developed lesions in the other limb within five months. They were all
      male cats, two years old or younger, and 15 had been neutered. The initial sign
      was a vague lameness which typically progressed, often acutely, to a more severe
      lameness. Radiography demonstrated radiolucency and loss of definition within the
      proximal femoral metaphysis, the femoral neck. In 12 cases there was a complete
      radiolucent line across the femoral neck. An excision arthroplasty was carried
      out on all the affected hips and the lameness resolved in all cases. The clinical
      and radiological signs suggest a primary bone resorption with secondary fracture
      of the femoral neck. The lesions have some similarities with Legg-Calve-Perthes'
      disease, traumatic fracture of the femoral neck, canine metaphyseal osteopathy,
      bacterial osteomyelitis and experimental feline herpes virus osteomyelitis.

PMID- 9519430
TI  - Canine piroplasmosis due to Babesia gibsoni: clinical and morphological aspects.

PMID- 9519431
TI  - Effect of culture conditions on the hatching ability of in vitro produced buffalo
      (Bubalus bubalis) embryos.

PMID- 9519432
TI  - Abdominal straining in a goat with a leiomyoma of the cervix.

PMID- 9519433
TI  - 'Animals under our care'--whose care, and for how long?

PMID- 9519434
TI  - Changes in milk purchasing arrangements.

PMID- 9519435
TI  - Intraperitoneal administration of whole blood as a treatment for anaemia in
      lambs.

PMID- 9519436
TI  - Extra-uterine pregnancy in a rabbit.

PMID- 9519437
TI  - Overview of nuclides for bone pain palliation.
AB  - A variety of radiopharmaceuticals has been used for systemic therapy to relieve
      pain from malignancies metastatic to bone, using electron emitting radionuclides
      either in ionic form or as labels for bone seeking compounds to irradiate locally
      at sites of metastases. The major complication comes from the absorbed dose to
      the bone marrow. Therefore, there has been a search for radionuclides with lower
      energy emissions and correspondingly shorter range in tissue. Some studies have
      shown that it is possible to delay the onset of new pain sites and perhaps
      increase life expectancy.

PMID- 9519439
TI  - Reactor-produced radionuclides at the University of Missouri Research Reactor.
AB  - A revolution in radiotherapy has been developing in recent years, based on more
      sophisticated targeting methods including radioactive intra-arterial
      microspheres, chemically-guided bone agents, labeled monoclonal antibodies, and
      isotopically-tagged polypeptide receptor-binding agents. The isotopes of choice
      for these applications are reactor-produced beta emitters such as Sm-153, Re-186,
      Re-188, Ho-166, Lu-177, and Rh-105. The University of Missouri Research Reactor
      (MURR) has been in the forefront of research into means of preparing, handling,
      and supplying these high specific activity isotopes in quantities appropriate not
      only for research, but also for patient trials in the U.S. and around the world.
      Considerable effort has been expended to develop techniques for irradiation,
      handling, and shipping isotopes worldwide. The MURR has also served as a highly
      reliable production source for isotopes, with one of the best operating histories
      of any isotope production reactor in the world.

PMID- 9519438
TI  - Radionuclide development at BNL for nuclear medicine therapy.
AB  - Radionuclides with medium energy beta emission and a several day half-life have
      often been viewed as attractive candidates for radioimmunotherapy. Among the most
      promising in this category are 47Sc, 67Cu, 153Sm, 188Re, and 199Au. The
      production of 67Cu, 153Sm, 199Au at BNL is summarized and the development of the
      latest candidate for this application, 47Sc, is described in detail. We also
      summarize the development of another important therapeutic radionuclide, 117mSn
      for bone pain palliation.

PMID- 9519441
TI  - The standardization of the potential bone palliation radiopharmaceutical
      117mSn(+4)DTPA.
AB  - Solutions containing the potential bone pain palliation radionuclide 117mSn, in
      chloride form and as a diethylenetriaminepentaacetate (DTPA) complex, have been
      standardized by 4 pi beta liquid scintillation (LS) spectrometry and 4 pi gamma
      ray spectrometry. Massic activities of the stock solutions were measured in order
      to determine dose calibrator settings for the solutions using commercial dose
      calibrators. Excellent agreement in the measurement of solution massic activity
      between the two techniques was achieved. The massic activity of 117mSnCl4 stock
      solution was found to be 38.62 +/- 0.23 MBq g-1 and 38.81 +/- 0.94 MBq g-1 with
      LS spectrometry and 4 pi gamma-ray spectrometry respectively. The respective
      values of the massic activity of the 117mSnDTPA stock solution with LS
      spectrometry and 4 pi gamma-ray spectrometry were 39.35 +/- 0.23 MBq g-1 and
      39.70 +/- 0.96 MBq g-1. Impurities were analyzed in several solutions and found
      to have emission rates on the order of 10(-4) to 10(-6) of the rate of the 117mSn
      emission at the end-of-bombardment. The largest impurities came from 113Sn and
      125Sn, the activation products of isotopic impurities present in the 117Sn
      target. The relative proportions of the various impurities were found to be
      highly dependent upon the source of 117Sn target material. The implications of
      choice of half-life used in the decay correction of 117mSn are discussed.

PMID- 9519440
TI  - Reactor-produced radioisotopes from ORNL for bone pain palliation.
AB  - The treatment of painful skeletal metastases is a common clinical problem, and
      the use of therapeutic radionuclides which localize at metastatic sites has been
      found to be an effective method for treatment of pain, especially for multiple
      sites for which the use of external beam irradiation is impractical. There are
      currently several metastatic-targeted agents radiolabeled with various
      therapeutic radionuclides which are in various stages of clinical investigation.
      Since neutron-rich radionuclides are produced in research reactors and often
      decay by emission of beta- particles, most radionuclides used for bone pain
      palliation are reactor-produced. Key examples of radionuclides produced by single
      neutron capture of enriched targets include rhenium-186 and samarium-153. In
      addition, generator systems are also of interest which provide therapeutic
      daughter radionuclides from the decay of reactor-produced parent radionuclides.
      One important example is rhenium-188, available from generators via decay of
      reactor-produced tungsten-188. Tin-117m is an example of a reactor-produced
      radionuclide which decays with the emission of low-energy conversion electrons
      rather than by beta- decay. Each of these agents and/or radionuclides has
      specific advantages and disadvantages, however, the ideal agent for bone pain
      palliation has not yet been identified. The goal of this paper is to briefly
      review the production and use of several reactor-produced radionuclides for bone
      pain palliation, and to discuss the role of the ORNL High Flux Isotope Reactor
      (HFIR) for the production of many of these radionuclides.

PMID- 9519442
TI  - Measurement standards for strontium-89 for use in bone palliation.
AB  - Strontium-89 standards have been prepared for use in calibrating instruments in
      the measurement chain from production in reactors to administration in the clinic
      or radiopharmacy. Alternate reactor production schemes were evaluated to yield
      high purity 89Sr with minimum 85Sr impurity. Following purification to remove
      radionuclidic impurities, samples of 89Sr were standardized by high-efficiency
      liquid-scintillation counting with a relative expanded uncertainty (intended to
      approximate two standard deviations) of 0.48%. A Standard Reference Material, SRM
      4426A, was prepared and distributed to radiopharmaceutical manufacturers and
      other customers. The standard sources of 89Sr were used in different geometries
      to calibrate high purity Ge semiconductor detectors, re-entrant ionization
      chambers and commercial radionuclide calibrators. The latter included Capintec
      dose calibrators and the Capintec beta C NaI(Tl) scintillation counter.

PMID- 9519443
TI  - A simple method of preparation for [123I]-(S)-(-)-IBZM.
AB  - Sterile, apyrogenic [123I]IBZM was prepared in a sealed, capped 'V' vial,
      followed by SEP-PAK C-18 cartridge purification, and then was placed under sealed
      vial condensation. The quantity of BZM present in the final product ranged from
      3.3-5.9 micrograms, as measured by a UV spectrophotometer at 254 and 308 nm.
      Animal biodistribution studies revealed that the [123I]IBZM prepared by this
      method which contained 5.9 micrograms of BZM, compared to the standard
      preparation method containing 0 microgram of BZM, resulted in identical brain
      uptakes at 15, 30, 60, and 120 min post-injection. The in vitro and in vivo
      studies demonstrated that a small amount of BZM presence in the final product did
      not affect the radiochemical purity, nor the D2 receptor binding capacity in the
      rat brain of [123I]IBZM. The preparation time can be shortened to 1.5 h compared
      with at least 2-4 h needed for the standard method of preparation. This factor
      may be important in routine clinical application.

PMID- 9519444
TI  - Numerical evaluation of the production of radionuclides in a nuclear reactor
      (Part I).
AB  - Numerical evaluation of nuclear transmutations is essential for optimization of
      radionuclide production. Accordingly, we have developed a generalized computer
      program called LAURA for predicting the production rates of radionuclides in a
      nuclear reactor. The program is generalized in the sense that it can be used for
      calculation of the production rate of any member of a network undergoing
      spontaneous decay and/or induced neutron transformation in a nuclear reactor. In
      this paper (Part I), we describe the mathematical basis for the development of
      LAURA. Expressions based on the Rubinson (1949) approach have been used for the
      evaluation of the depletion functions. This method is also valid when some of the
      depletion constants have identical values; thus, the approximate solution of
      Raykin and Shlyakhter (1989) can be used to account for the effects of feedback
      due to alpha decay.

PMID- 9519445
TI  - Numerical evaluation of the production of radionuclides in a nuclear reactor
      (Part II).
AB  - A computer program called LAURA has been developed to predict the production
      rates of any member of a nuclei network undergoing spontaneous decay and/or
      induced neutron transformation in a nuclear reactor. The theoretical bases for
      the development of LAURA were discussed in Part I. In particular, in Part I, we
      described how an expression based on the Rubinson (1949) approach is used to
      evaluate the depletion function. In this paper (Part II), we describe the full
      simulation of radionuclide production including the decomposition of a reaction
      network into independent linear chains, provisions for periodic reactor shutdown
      and restart, and implementation of an approximate solution given by Raykin and
      Shlyakhter (1989) to account for the effect of feedback due to alpha decay. Also
      included are some examples which demonstrate possible uses for LAURA.

PMID- 9519446
TI  - Seasonal variations of 226Ra and 222Rn in mineral spring waters of Aguas de
      Prata, Brazil.
AB  - In this paper the activity concentrations of 226Ra and 222Rn were assayed in the
      mineral spring waters of Aguas da Prata in order to evaluate the seasonal
      variations of such radionuclides. The results obtained were related to the
      chemical composition of the water as well as to the lithology of the aquifer and
      temperature. Higher activity concentrations up to 1.8 x 10(3) mBq L-1 for 226Ra
      and 1.2 x 10(2) Bq L-1 for 222Rn have been observed in waters with low levels of
      soluble salts. Waters which present high levels of carbonate and sulphate salts
      showed maximum values of 2.5 x 10(2) mBq L-1 for 226Ra and 2.7 x 10(1) Bq L-1 for
      222Rn. This behaviour is mainly due to the physico-chemical properties of these
      radionuclides in water as well as to the lithologic structure of the aquifers.

PMID- 9519447
TI  - Application of nitrite reductase from Alcaligenes faecalis S-6 for nitrite
      measurement.
AB  - The enzymatic reaction of nitrite reductase (NIR) from Alcaligenes faecalis S-6
      was applied to the measurement of nitrite. NIR was immobilized on the surface of
      a gold electrode using filter paper and a dialysis membrane, and used as a
      working electrode in a three-electrode system. Amperometric methods were applied
      using NIR and the electron mediator 1-methoxy PMS (1-methoxy-5-methylphenazinium
      methylsulfate). The decrease in cathodic current showed a correlation to nitrite
      concentration over the range 0-1 mg/l. Measurements using a batch-flow type
      system gave a lower detection limit of 0.01 mg/l. This is sufficient for the
      detection of nitrite in natural waters.

PMID- 9519448
TI  - Development of electrochemical immunosensing systems with renewable surfaces.
AB  - The repeated use of immunochemically modified solid phases in electrochemical
      immunosensor analysis is the driving interest of this work. Two new strategies
      have been developed. One of these strategies is aimed at the development of a
      manual methodology. It comprises the construction of amperometric immunosensors
      based on rigid biocomposites. These biocomposites are formed by a conducting
      polymer composite matrix that acts as a reservoir of an immobilized immunologic
      material. The surface of the biocomposite can be renewed by a simple polishing
      procedure. The second strategy involves the design of an automatic methodology.
      It features an immunochemical analytical system using flow injection techniques.
      The potentiometric detection uses a solid phase formed by immunologic reagents
      immobilized in magnetic particles. These particles are fixed to the sensor with
      the use of a magnetic field. The renewal of the reactive surface is achieved by
      the release and activation of the restraining magnetic field and the manipulation
      of the flow. The analytical properties of these immunosensors were evaluated
      measuring RIgG using a competitive technique and measuring GaRIgG with a sandwich
      methodology. The labelling enzymes of the immunoconjugates were peroxidase in
      amperometric measurements and urease in potentiometric measurements.

PMID- 9519449
TI  - Influence of calcium on glucose biosensor response and on hydrogen peroxide
      detection.
AB  - Of small species capable of reaching a platinum working electrode from biological
      samples, calcium cations have been found to inhibit significantly glucose
      biosensor responses. The sensitivities to glucose of sensors immersed in
      carbonate buffer saline solutions decreased when 0.5 mM calcium chloride was
      added. The degree of inhibition was proportional to the glucose response in the
      absence of calcium (0-17% of the normalized current). Likewise, sensor
      sensitivities to hydrogen peroxide decreased, in the 5-90% range, in the presence
      of 0.5 mM calcium. Bare Pt-lr wires show a reversible inhibition of hydrogen
      peroxide sensitivity. This reversible inhibition is directly related to the
      decrease of hydrogen peroxide oxidation rate at the platinum anode: this has been
      evidenced, using rotating disk electrodes, by plotting Koutecky-Levich plots.
      Such inhibition has been found both for free and chelated calcium cations at
      levels below 1 mM. Several hypotheses for possible reactions between platinum,
      hydrogen peroxide and calcium are discussed.

PMID- 9519450
TI  - Continuous flow immunosensor for atrazine detection.
AB  - The hapten atrazine was detected under continuous flow conditions using a micro
      column which contained immobilized monoclonal antibodies (Ab) against atrazine
      and atrazine labeled with alkaline phosphatase (An*). The equilibrium of the
      antibody-hapten system, was achieved by a continuous flow of the tracer An*
      through the micro-column containing the immobilized antibodies. The activity of
      the tracer was monitored continuously, after the micro-column, by an amperometric
      detector using p-hydroquinone phosphate as substrate. When pulses of unlabeled
      atrazine (An) were added to the An* flowing continuously through the micro
      column, An* bound to the antibody was displaced, with a consequent change of the
      detector signal. By this method atrazine concentrations in the range 9-180
      micrograms/l were monitored under conditions of continuous operation. Since the
      equilibrium condition for the system Ab-An* was continuously restored by the flow
      of An* through the micro-column the regeneration of the antibody was not
      required.

PMID- 9519451
TI  - Amperometric biosensor with a composite membrane of sol-gel derived enzyme film
      and electrochemically generated poly(1,2-diaminobenzene) film.
AB  - A sol-gel silicate-based biosensor for glucose was made by utilizing a composite
      membrane of sol-gel enzyme film and electrochemically generated poly(1,2
      diaminobenzene) film to improve the selectivity of the sol-gel enzyme sensors.
      The stability of the sensor was improved by exposing the enzyme layer to
      glutaraldehyde vapor. The glucose sensor responded rapidly (ca. 15 s) to glucose
      at 0.6 V (versus Ag/AgCl), without any interferences from electroactive species
      such as L-ascorbate and urate below 0.2 mM. Reliable results were obtained in the
      assays of glucose in controlled human sera, with both the steady-state and flow
      injection measurements. Subsequently, the same sol-gel procedure was applied to
      the preparation of the sensors for galactose and cholesterol. The galactose and
      cholesterol sensors responded rapidly to galactose and cholesterol, respectively,
      although the sensitivity of these sensors was inferior to that of glucose sensor.

PMID- 9519452
TI  - Chemiluminescent biosensors based on porous supports with immobilized peroxidase.
AB  - Combining a sensitive and fast chemiluminescence detection method with novel
      immobilization methods for horseradish peroxidase (HRP) has enabled us to develop
      sensitive sensors for hydrogen peroxide and the herbicide 2,4
      dichlorophenoxyacetic acid (2,4-D). HRP biospecific immobilization was shown to
      have well-defined advantages in terms of a higher specific activity of the enzyme
      of the surface and a greater sensitivity in the enhanced chemiluminescence (ECL)
      reaction. The lower detection limit for hydrogen peroxide was 0.025 nmol with HRP
      immobilized on nitrocellulose membrane through avidin-biotin linkage. An
      immunosensor for the detection of 2,4-D provides a lower detection limit of 0.2
      microgram/l with specific antibodies covalently immobilized on photoactivated
      nylon. The assay with chemiluminescent detection was also characterized with a
      wider concentration range when compared with the colorimetric assay.

PMID- 9519453
TI  - Electrosynthesized non-conducting polymers as permselective membranes in
      amperometric enzyme electrodes: a glucose biosensor based on a co-crosslinked
      glucose oxidase/overoxidized polypyrrole bilayer.
AB  - A glucose amperometric biosensor based on glucose oxidase immobilized on an
      overoxidized polypyrrole (PPyox) platinum modified electrode, by glutaraldehyde
      co-crosslinking with bovine serum albumine, is described. The advantages of
      covalent immobilization techniques (e.g. high loading and long-term stability of
      the enzyme) are coupled with the excellent interferent rejection of
      electrosynthesized non-conducting polymers. The sensor showed an apparent
      Michaelis-Menten constant of 16 +/- 0.8 mM, a maximum current density of 490
      microA/cm2 and a shelf lifetime of at least 3 months. Ascorbate, urate, cysteine
      and acetaminophen at their maximum physiological concentrations produced a
      glucose bias in the low micromolar range. Flow-injection response was linear up
      to 20 mM glucose with typical sensitivity of 84.0 +/- 1.5 nA/mM. The sensor was
      tested for glucose determination of untreated serum samples from both normal and
      diabetic subjects; results of amperometric assay compared well with those
      obtained by a standard enzymatic-colorimetric method.

PMID- 9519454
TI  - Immunosensors: electrochemical sensing and other engineering approaches.
AB  - This article overviews the engineering approaches and the recent trends in the
      development of alternative immunoassay systems. A brief description of the main
      principles and limitations of conventional immunoassay is given. Immunosensing
      approaches overcoming these limitations are discussed. Alternatives to
      traditional immunoassay systems are discussed in terms of the enhancement of
      immunointeraction processes and in terms of the various detection principles.
      Applications of flow-injection techniques to the development of immunosensing
      systems are presented. Immunosensors are categorized based on the detection
      principle employed, as immunoelectrodes (electrochemical immunosensors),
      piezoelectric immunosensors, or as sensors based on optical detection of the
      immunointeraction. The discussion focuses on electrochemical immunosensors. In
      conclusion, the engineering issues involved in immunosensor development are
      outlined and trends towards practical applications are discussed.

PMID- 9519455
TI  - Current awareness in biosensors & bioelectronics.

PMID- 9519456
TI  - The effects of cadmium exposure on the cytology and function of primary cultures
      from rainbow trout.
AB  - Cultured epidermal cells from explants of skin of rainbow trout were used to
      study the cytological and functional changes following sublethal exposure to
      cadmium stress. The aim was to develop diagnostic markers for ecotoxicology.
      Cultures were exposed to the pollutant for 48 h. Cell structural and cytological
      changes were established by light and electron microscopy. Metabolic alterations
      were detected by immunohistochemistry. The relation between the initiation of
      cellular alterations and cadmium concentrations was compared in cultures exposed
      in commercially-available serum-free and serum-containing medium. The expression
      of stress proteins (metallothionein and heat shock protein) was also studied.
      Rainbow trout epithelial cells exposed to cadmium showed typical morphological
      changes indicative of cell death by apoptosis. Sublethal exposure also resulted
      in cellular metabolic disturbances with increased deposits of glycogen. Increased
      melanization was also observed. These changes appeared at lower concentrations of
      cadmium when cells were exposed in serum-free media than in serum-containing
      media. Cadmium induced the expression of heat shock proteins but not of
      metallothioneins. The results broadly confirm in vivo findings for cadmium
      toxicity and suggest that this in vitro technique may have applications in
      aquatic toxicology.

PMID- 9519457
TI  - Mechanism of citrinin-induced dysfunction of mitochondria. VI. Effect on iron
      induced lipid peroxidation of rat liver mitochondria and microsomes.
AB  - The inhibition by citrinin (CTN) of lipid peroxidation of mitochondria, sub
      mitochondrial particles (SMP) and microsomes was studied. This effect was
      reversed by the presence of high concentrations of Fe3+ (0.4 and 0.5 mM),
      suggesting chelation of the mycotoxin with iron or interference in the reduction
      of Fe3+.

PMID- 9519458
TI  - Functional expression of basolateral Cl-/HCO3- exchange from rat jejunum in
      Xenopus laevis oocytes.
AB  - Poly(A)+ RNA isolated from rat jejunum was injected into Xenopus laevis oocytes
      and expression of Cl-/HCO3- antiport was investigated by means of 36Cl- uptake.
      Two days after injection of 50 ng of poly(A)+ RNA, Cl- uptake was significantly
      increased with respect to water-injected oocytes. The expressed transport was
      inhibited by 0.2 mM DIDS, whereas endogenous Cl- uptake was unaffected by this
      disulphonic stilbene. After sucrose density gradient fractionation, the highest
      expression of DIDS-sensitive Cl- uptake was detected with mRNA size fraction of
      about 2-4 kb in length. The expressed Cl- uptake can occur against a Cl-
      concentration gradient and is unaffected by the known Cl- channel blocker
      anthracene-9-carboxylic acid. Cl- transport mechanism has properties similar to
      jejunal basolateral. Cl-/HCO3- exchange with regard to Na+ dependence.

PMID- 9519459
TI  - Percentage of phagocytosis, production of O2.-, H2O2 and NO, and antioxidant
      enzyme activities of rat neutrophils in culture.
AB  - Changes in the integrity, ultrastructure, phagocytosis capacity, and production
      of H2O2, O2.- and NO2- were evaluated in cultured neutrophils. The activities of
      the antioxidant enzymes (catalase-CAT, superoxide dismutase-SOD and glutathione
      dependent peroxidase-GSH-Px) were measured under similar conditions. The
      integrity of the cells remained unchanged up to 18 h. After 24 h, the number of
      viable cells in culture dropped by 16 per cent. The percentage of viable cells in
      culture was of 72 per cent even after 72 h. An ultrastructural analysis of the
      cells was carried out after 3, 6, 12, 24, 48, and 72 h in culture. Neutrophils
      started developing morphologic changes after 24 h: decreased cell volume,
      abundant vacuoles (mainly around the nucleus), and also the presence of
      autophagic vacuoles. This period was then chosen for the study of neutrophil
      function and antioxidant enzyme activities. Neutrophils cultured for 24 h
      presented reduced phagocytosis capacity. The rates of production of H2O2 and O2.-
      remained unchanged after 24 h in culture. Concomitantly, these cells were also
      able to produce NO in significant amounts. The production of O2.- in response to
      PMA stimulus was lowered in 24-h cultured cells. Possibly, the production of
      oxygen and nitrogen reactive species accomplished with a decrease in the
      activities of CAT and GSH-Px play a key role for the process of apoptosis which
      takes place in neutrophils under these conditions.

PMID- 9519460
TI  - Oxygen free radical scavenger properties of dehydroepiandrosterone.
AB  - The microsomes from dehydroepiandrosterone (DHEA)-supplemented animals are good
      hydroxyl radical scavengers, as demonstrated through electron spin resonance and
      deoxyribose degradation. The ability of DHEA-supplemented microsomes to react
      with superoxide radical was also demonstrated through the inhibition of nitroblue
      tetrazolium reduction determined by superoxide radicals produced in a
      hypoxanthine-xanthine oxidase system. DHEA-enriched microsomes, obtained from
      acutely DHEA-treated rats, become resistant to iron-dependent lipid peroxidation
      triggered by H2O2/FeSO4 and ascorbate/FeSO4. The direct addition of DHEA to
      microsomes from untreated rats failed to prevent iron-dependent lipid
      peroxidation, even if the microsomes were preincubated with DHEA for up to 15
      min, indicating that in vivo transformation is required before antioxidant action
      can be exerted.

PMID- 9519461
TI  - Primary role of Kupffer cell-hepatocyte communication in the expression of
      oxidative stress in the post-ischaemic liver.
AB  - It has been reported that hepatocyte metabolism and function can be modulated by
      the activated Kupffer cell through the release of different biomolecules like
      cytokines, eicosanoids, oxygen free radicals and enzymes. In relation to these
      paracrine factors involved in circuits of intercellular communication, the
      existence of a hepatic oxygen sensor located in the Kupffer cell has been
      postulated. According to this postulate the oxygen metabolism of the liver
      parenchymal cells could be under the control of the Kupffer cells. In order to
      study the role of the Kupffer cell in the reperfusion syndrome of the liver, a
      lobular ischaemia-reperfusion model was performed in rats with or without
      previous treatment with gadolinium chloride to block Kupffer cell function.
      Spontaneous chemiluminescence of the liver surface, oxygen uptake by tissue
      slices and tertbutyl hydroperoxide-initiated chemiluminescence determinations
      were performed to evaluate the oxygen metabolism and the oxy-radical generation
      by the liver. The lower basal photoemission, in parallel with a lower basal
      oxygen uptake registered in the hepatic lobes from the animals pretreated with
      gadolinium chloride clearly indicates that the gadolinium chloride-dependent
      functional inhibition of Kupffer cell leads to a downregulation of oxygen
      metabolism by the liver. Moreover, the intensity of oxidative stress exhibited by
      the postischaemic lobes appears to be closely linked with the Kupffer cell
      activity. On the basis of the data obtained we propose that a paracrine circuit
      between activated Kupffer cell and hepatocytes is an early key event in the
      induction of postischaemic oxidative stress in the liver. Furthermore the
      interference with the mitochondrial electron flow by some biomolecules released
      from the activated Kupffer cell, such as tumour necrosis factor, interleukins,
      eicosanoids, etc., would increase the rate of generation of reactive oxygen
      species by the inhibited mitochondrial respiratory chain.

PMID- 9519462
TI  - Polycyclic aromatic hydrocarbons in Laurus nobilis leaves as a measure of air
      pollution in urban and rural sites of Tuscany.
AB  - The levels of 9 polycyclic aromatic hydrocarbons (PAHs) 6 of which carcinogenic
      were measured in the leaves of evergreen tree (Laurus nobilis) sampled in 13
      locations in summer and winter in Tuscany, Italy. The carcinogenic PAH levels
      were correlated with the PAH air levels sampled at the same site. Samples from
      larger towns had higher PAH levels than those from medium and small towns. Leaves
      collected in the center of larger cities had higher carcinogenic PAH levels than
      samples from residential areas indicating that vehicular traffic is the main PAH
      source. Carcinogenic PAH levels in leaves collected in the winter in medium towns
      were considerably higher than expected, probably due to domestic heating. These
      findings demonstrate that air quality in terms of PAH contamination is not
      markedly different in towns of different size in Tuscany.

PMID- 9519463
TI  - A novel method to determine uptake and elimination kinetics of volatile chemicals
      in fish.
AB  - The development of an exposure system suitable for studying the uptake and
      elimination kinetics in fish of volatile chemicals is discussed. Static exposure
      of the fish is in a closed system containing water and air. Automated sampling
      and analysis of the air provides a concentration-time profile that is then fit to
      differential equations using numerical integration methods. Assumptions for the
      mathematical description of the system are a) instantaneous distribution of
      chemical between water and air and b) a first order one-compartment model
      describes the kinetics of chemical in fish. Uptake and elimination rate constants
      in fathead minnows (Pimephales promelas) were determined for a mixture of
      benzene, toluene, monochlorobenzene, monobromobenzene, and 1,3-dichlorobenzene.
      No significant biotransformation was observed for any of the compounds. Uptake
      rate constants increased with increasing octanol-water partition coefficient
      (Kow), whereas the elimination rate constants were inversely related to Kow.

PMID- 9519464
TI  - Determination of aflatoxicol in human urine by immunoaffinity column clean-up and
      liquid chromatography.
AB  - A method for the determination of aflatoxicol in urine has been developed. The
      urine samples were cleaned up by an automated procedure using immunoaffinity
      columns before analysis by high-performance liquid chromatography and
      fluorescence detection. Post-column derivatization with bromine allowed the
      simultaneous determination of aflatoxicol and aflatoxins B1, B2, G1, G2, M1, and
      Q1. Average recovery of aflatoxicol was 99% in the range 4-40 pg ml-1 of spiked
      urine samples. The relative standard deviations were all between 1% and 3%. The
      limit of detection was 1 pg ml-1 urine. Authentic samples from exposed feed
      factory workers were analysed, but aflatoxin levels were found to be below the
      detection limit.

PMID- 9519465
TI  - Reflections on the biology, morphology and ecology of the Macrochelidae.
AB  - The Macrochelidae is a cosmopolitan family of predatory mesostigmatic mites, many
      of which occupy specialized and often unstable habitats. Most known species have
      adapted to life in dung deposits where prey is plentiful and the potential exists
      for rapid population growth. Phoresy on co-occurring flying insects plays a vital
      role in assuring niche continuity for macrochelids in these ephemeral substrates.
      A brief general review of some of the earlier highlights of macrochelid research
      is presented, followed by a discussion of the emergence of phoresy as a major
      survival strategy in the Macrochelidae associated with dung beetles. Special
      emphasis is placed on the behavioural and chemical mechanisms that mediate
      phoretic specificity of macrochelid species in the unique n-dimensional universes
      of their scarab hosts. Phylogenetic analysis of selected phoretic and non
      phoretic macrochelid taxa has shown a strong correlation between phoretic state
      and evolutionary position, indicating that an increasing commitment to phoresy in
      the Macrochelidae is correlated with an advance from early derivative to terminal
      taxa. Laboratory and field observations have confirmed the importance of
      chemical, behavioural and ecological factors in maintaining the integrity of the
      relationship between phoretically specific macrochelids and their dung beetle
      hosts.

PMID- 9519467
TI  - New developments and applications in quantitative electron spectroscopic imaging
      of iron in human liver biopsies.
AB  - Reliable iron concentration data can be obtained by quantitative analyses of
      image sequences, acquired by electron spectroscopic imaging. A number of
      requirements are formulated for the successful application of this recently
      developed in situ quantitative type of analysis. A demonstration of the
      procedures is given. By application of the technique it is established that there
      are no significant differences in the average iron loading of structures analysed
      in liver parenchymal cells of a patient with an iron storage disease, before and
      after phlebotomy. This supports the hypothesis that the process of iron unloading
      is an organelle specific process. Measurement of the binary morphology,
      represented by the area and contour ratio of the iron containing objects revealed
      no information about differences between the objects. This finding contradicts
      the visual suggestion that ferritin clusters are more irregularly shaped than the
      other iron objects. Also, no differences could be found in this sense between the
      situations before and after phlebotomy. With respect to the density appearance,
      objects that have an inhomogeneous iron loading averagely contain more iron. This
      observation does correspond well with the visual impression of the increasingly
      irregular appearance of more well-loaded structures.

PMID- 9519466
TI  - Expressed sequenced tags and new genes from the cattle tick, Boophilus microplus.
AB  - We used the expressed sequenced tags (ESTs) approach to study the genome of the
      cattle tick Boophilus microplus. One hundred and forty-two of our 234 unique ESTs
      were from genes not previously identified from ticks, mites or any other
      arachnids. The largest class of identified ESTs (29%) was from genes involved in
      transcription and translation. Ninety-one ESTs (39% of all ESTs) did not match
      any sequences in international databases; some of these may be specific to ticks.
      Thirteen percent of our ESTs were from ribosomal proteins and two ESTs were for
      genes implicated in resistance to pesticides.

PMID- 9519468
TI  - Intracellular mapping of 4'-deoxy-4'-iododoxorubicin in sensitive and multidrug
      resistant cells by electron spectroscopic imaging.
AB  - Electron spectroscopic imaging (ESI) was employed to study, with high spatial
      resolution, the intracellular distribution of the halogenated derivative of
      doxorubicin 4'-deoxy-4'-iododoxorubicin (IDX) in sensitive and multidrug
      resistant human breast carcinoma cells. Both ESI and electron energy loss
      spectroscopy (EELS) observations confirmed results obtained with flow cytometry
      (FC), laser scanning confocal microscopy (LSCM) and secondary ion mass
      spectrometry (SIMS). Moreover, ESI allowed us to obtain a more detailed
      intracellular localization of IDX. Our results confirm that nuclear DNA
      represents the main intracellular target for IDX and that the Golgi apparatus is
      involved in the intracellular transport of the drug.

PMID- 9519470
TI  - High resolution microanalysis and three-dimensional nucleosome structure
      associated with transcribing chromatin.
AB  - The nucleosome is the ubiquitous and fundamental DNA-protein complex of the
      eukaryotic chromosome, participating in the packaging of DNA and in the
      regulation of gene expression. Biophysical studies have implicated changes in
      nucleosome structure from chromatin that is quiescent to active in transcription.
      Since DNA within the nucleosome contains a high concentration of phosphorus
      whereas histone proteins do not, the nucleosome structure is amenable to
      microanalytical electron energy loss mapping of phosphorus to delineate the DNA
      within the protein-nucleic acid particle. Nucleosomes associated with
      transcriptionally active genes were separated from nucleosomes associated with
      quiescent genes using mercury-affinity chromatography. The three-dimensional
      image reconstruction methods for the total nucleosome structure and for the 3D
      DNA-phosphorus distribution combined quaternion-assisted angular reconstitution
      of sets of single particles at random orientations and electron spectroscopic
      imaging. The structure of the active nucleosome has the conformation of an open
      clam-shell, C- or U-shaped in one view, elongated in another, and exhibits a
      protein asymmetry. A three-dimensional phosphorus map reveals a conformational
      change in nucleosomal DNA compared to DNA in the canonical nucleosome structure.
      It indicates an altered superhelicity and is consistent with unfolding of the
      particle. The results address conformational changes of the nucleosome and
      provide a direct structural linkage to biochemical and physiological changes
      which parallel gene expression.

PMID- 9519469
TI  - Use of a mass-thickness marker to estimate systematic errors and statistical
      noise in the detection of phosphorus by electron spectroscopic imaging.
AB  - The element signal obtained from electron-energy-filtered micrographs depends on
      the systematic error in calculating the background and on the noise in the
      background-corrected image. Both systematic error and statistical fluctuation of
      the background can be assessed experimentally with a specimen that combines the
      element-containing feature with a mass-thickness marker. The approach is
      described for the mapping of phosphorus in turnip yellow mosaic viruses prepared
      on a supporting carbon film of variable thickness. The thickness modulations are
      produced by the additional deposition of heat-evaporated carbon through a second
      grid used as a mask. The three-window power-law method and the two-window
      difference method are compared. With the three-window power-law method, the mass
      thickness modulations of the marker are still visible in the map, indicating a
      systematic error for the calculated background. In addition, the intensity
      profile over the area of the thick carbon film is broader than in the map
      corrected by the two-window method, indicating a higher level of noise. With the
      two-window difference method, mass-thickness contrast was practically eliminated
      due to an improved protocol that uses the mass-thickness marker to calculate the
      scaling factor: instead of scaling the grey-level of a single background feature,
      the pre-edge image is scaled to the contrast of the marker area in the image
      acquired at the element-specific energy loss.

PMID- 9519471
TI  - X-ray microanalysis of uterine epithelial cells in culture.
AB  - The ionic composition of the uterine fluid, secreted by the endometrium, is of
      importance for fertilization and embryonic development. Little, however, is known
      about the ion transport mechanisms in the uterine epithelial cells. Because it is
      difficult to study ion transport in this tissue in situ, a method was developed
      to culture mouse uterine epithelial cells for X-ray microanalysis in the electron
      microscope, in order to allow the study of ion transport. Our data suggest the
      presence of a number of ion transport mechanisms in the cultured uterine
      epithelial cells. The cells appear to possess a ouabain-sensitive Na(+)-K(+)
      ATPase, an amiloride-sensitive Na(+)-H+ antiporter, cAMP- and Ca(2+)-activated
      chloride channels, and volume-activated chloride efflux and influx mechanisms. In
      addition, chloride efflux can be stimulated by cholinergic and alpha-adrenergic
      agonists. Only a few of these mechanisms had been studied previously in the
      uterine epithelium.

PMID- 9519472
TI  - The role of 18-methyleicosanoic acid in the structure and formation of mammalian
      hair fibres.
AB  - Although branched chain fatty acids perform many functions in biological systems,
      the importance of the anteiso 18 methyleicosanoic acid (MEA) has only recently
      been recognized. In this first review on MEA its role and distribution is
      explored. MEA has been found in minor amounts in the fatty acid components of a
      wide range of biological materials, but the current interest results from it
      being the major covalently bound fatty acid in mammalian hair fibres, a finding
      which is unusual because protein-bound fatty acids are typically straight-chain,
      even-numbered acids (C14-C18). MEA is released by surface restricted reagents
      indicating that it is located exclusively in or on the surface of the cuticle
      cells, a conclusion that has been verified by analysis of isolated cuticle cells,
      X-ray photoelectron spectroscopy (XPS) and secondary-ion mass spectroscopy (SIMS)
      studies support these results in that they show the surface of the cuticle to be
      predominantly hydrocarbon. When either neutral hydroxylamine or acidic chlorine
      solutions are applied to hair and wool fibres fatty acids are liberated,
      indicating the presence of thioester bonds. Calculations, based on fatty acid and
      amino acid analysis, indicate that approximately one residue in 10 of the
      cuticular membrane protein is a fatty acid thioester of cysteine. Removal of this
      covalently linked fatty acid renders the fibre hydrophilic, thus offering a
      chemical explanation for many technological and cosmetic treatments of mammalian
      fibres. Examination of the fibre surface and that of isolated cuticle cells by
      transmission electron microscopy (TEM) confirms the presence of a thin non
      staining continuous layer surrounding the cuticle cells. Alkaline treatments
      which remove the bound fatty acids were found to disrupt this layer. TEM
      examination of developing hair fibres has indicated that the fatty acid layer on
      the upper surface and scale edges of the cuticle cell differs from that of the
      underside of the cell. Similar structural studies of hair from patients with
      maple syrup urine disease (MSUD) support the findings that thioester-bound MEA is
      limited to the upper surface of fibre cuticle cells. The current model proposed
      for the boundary layer consists of crosslinked protein with surface thioester
      linked fatty acids, forming a continuous hydrophobic layer on the upper surface
      and scale edges of the cells.

PMID- 9519473
TI  - On the determination of internal nodes of an evolutionary dendrogram.
AB  - In this communication the determination of intermediary nodes in evolutionary
      dendrograms of proteins is analyzed, based on the molecular mechanisms involved
      in these transitions and the probability of acceptance of the amino acid
      substitutions.

PMID- 9519474
TI  - De novo peptide sequencing in an ion trap mass spectrometer with 18O labeling.
AB  - De novo peptide sequencing in an ion trap mass spectrometer coupled on-line with
      a capillary HPLC using 18O labeling provides a viable alternative to the method
      using the combination of nanospray, 18O labeling and a quadrupole/time-of-flight
      mass spectrometer. Seven to sixteen amino acid residues can be sequenced from the
      liquid chromatography/randem mass spectrometry (LC/MS/MS) spectra. This approach
      combines the benefit of capillary LC and the high sensitivity of the ion trap
      operated in the MS/MS mode. The wide availability of the LCQ mass spectrometer
      makes this approach readily adaptable to the biological mass spectrometry
      community.

PMID- 9519476
TI  - On the origin of the abundance distribution of apomyoglobin multiply charged ions
      in electrospray mass spectrometry.
AB  - The abundance distribution of multiply charged ions produced during the
      electrospray process is thought to depend on the initial conformational state of
      the analyte in solution and on solution chemistry, but with some proteins,
      including apomyoglobin, the correlation between solution and mass spectrometry
      data is unclear. In this study, we compare our results obtained by mass
      spectrometry with available data describing conformations and average number of
      charges of apomyoglobin in solution. A good correlation between average number of
      charges in solution and in the mass spectrum is only found for the pH 4.2
      solution. We propose that the discrepancies between solution and electrospray
      ionization mass spectrometry observed with apomyoglobin under other solution
      conditions can be mainly explained by (1) a preferential fragmentation of the
      highly charged ions in the source and (2) a variation of pH in the droplets
      during the electrospray process.

PMID- 9519475
TI  - Application of a generic fast gradient liquid chromatography tandem mass
      spectrometry method for the analysis of cytochrome P450 probe substrates.
AB  - A liquid chromatography tandem mass spectrometry (LC/MS/MS) method has been
      developed for the fast routine analysis of selected CYP450 probe substrate
      metabolites in microsomal incubations, with no sample pretreatment. This has
      allowed fast and simple assessment of the potential effects which drug candidates
      may or may not have on the metabolism of specific CYP450 probe substrates,
      providing information which can then be used to rationalize in vivo interaction
      studies required in the clinic. This methodology takes advantage of fast gradient
      chromatography as a generic means of sample separation and analysis. It provides
      high throughput analysis compared to conventional gradient HPLC, with no
      significant loss in chromatographic performance.

PMID- 9519477
TI  - High-performance liquid chromatography tandem mass spectrometry procedure with
      automated solid phase extraction sample preparation for the quantitative
      determination of paclitaxel (Taxol) in human plasma.
AB  - A sensitive, specific, accurate and reproducible analytical method was developed
      and validated for the quantitation of the anticancer agent paclitaxel in human
      plasma. This procedure is based on high performance liquid chromatography/ion
      spray-tandem mass spectrometry. This methodology is highly specific because a
      MS/MS technique (multiple reactant-ion monitoring, MRM) was used for both
      paclitaxel and its internal standard. The use of a fully automated solid phase
      extraction procedure, using a CN Sep-pak cartridge, to improve the detection
      limit and quantification limit of paclitaxel in human plasma samples, was
      evaluated. The method involves the addition of methyl-paclitaxel as internal
      standard (i.s.). The retention times of paclitaxel and the I.S. were 2.8 and 4.0
      min., respectively. The assay was linear over the range 5 to 500 ng/mL, with a
      quantification limit of 5 ng/mL having a coefficient of variation (c.v.) < 10%.
      Standard calibration curves, performed on three different days, had correlation
      coefficients always greater than 0.998. The intra and inter-day precision were
      within 12%, and accuracy was included in the range 102-110%. Paclitaxel recovery
      assessed at 15,250 and 500 ng/mL, was determined to be greater than 85%. The
      assay is applicable to clinical pharmacokinetic studies.

PMID- 9519478
TI  - Dual parallel mass spectrometers for analysis of sphingolipid,
      glycerophospholipid and plasmalogen molecular species.
AB  - Analysis of phospholipids was performed using a liquid chromatographic separation
      with two mass spectrometers in parallel providing electrospray ionization (ESI)
      and atmospheric pressure chemical ionization (APCI) data simultaneously from a
      triple quadrupole instrument and a single quadrupole instrument, respectively.
      The output from UV-Vis and evaporative light scattering detectors were also
      acquired by the two mass spectrometers, respectively, for four detectors overall.
      This arrangement was used to identify and calculate area percents for molecular
      species of dihydrosphingomyelin (DHS) and sphingomyelin (SPM) in commercially
      available bovine brain SPM, in human plasma extract and in porcine lens extract.
      Molecular species of phosphatidylethanolamine and its plasmalogen, and
      phosphatidylcholine and its plasmalogen were identified and semi-quantitative
      analysis performed. Commercially available bovine brain SPM was found to contain
      11.5% DHS and 88.5% SPM. The only DHS molecular species identified in human
      plasma was 16:0-DHS, at or below 1% of the sphingolipid content. Porcine lens
      membranes were found to contain 14.4% DHS and 85.6% SPM. Other findings reported
      here include: (1) phospholipids were found to undergo dimerization in the
      electrospray source, giving masses representing combinations of species present.
      (2) Triacylglycerols gave usable mass spectra under electrospray ionization
      conditions, as well as under APCI-MS conditions. (3) Triacylglycerols gave
      ammonium adducts as base peaks in their APCI mass spectra, which reduced
      fragmentation and increased the proportions of molecular ions. (4) Mass spectra
      were obtained for phospholipids which underwent both protonation and sodium
      adduct formation in different chromatographic runs.

PMID- 9519479
TI  - Metabolic engineering for the production of carotenoids in non-carotenogenic
      bacteria and yeasts.
AB  - The crt gene clusters responsible for the biosynthesis of carotenoids such as
      lycopene, beta-carotene and astaxanthin have been isolated from carotenogenic
      bacteria such as Erwinia species and the marine bacterium Agrobacterium
      aurantiacum. The functions of the individual genes have been identified. The
      first substrate of the enzymes encoded by the Erwinia crt clusters is farnesyl
      pyrophosphate which is not only the precursor for carotenoid biosynthesis but
      also sterols, dolichols and other numerous isoprenoid compounds. Escherichia coli
      does not naturally synthesize carotenoids, but by using the carotenogenic genes
      recombinant strains accumulating lycopene, beta-carotene and astaxanthin have
      been produced. Other non-carotenogenic bacteria such as Zymomonas mobilis have
      also been engineered to produce beta-carotene by the introduction of the
      corresponding crt genes. A gene capable of enhancing carotenoid levels in E. coli
      has also been isolated from cDNA libraries of the yeast Phaffia rhodozyma and the
      green alga Haematococcus pluvialis. This gene has been found to encode an
      isopentenyl pyrophophate isomerase. It has further been shown that the edible
      yeasts Candida utilis as well as Saccharomyces cerevisiae, which possess no
      carotenoid biosynthetic pathway, acquire the ability to produce carotenoids, when
      the carotenogenic genes are expressed under the control of yeast-derived
      promoters and terminators. It has been observed in the yeasts S. cerevisiae and
      C. utilis carrying the lycopene biosynthesis genes that ergosterol content is
      decreased by 10 and 35%, respectively. It is therefore likely that the carbon
      flux for the ergosterol biosynthesis has been partially directed from farnesyl
      pyrophosphate to a new pathway for the lycopene biosynthesis. Further, the
      expression of a truncated gene which codes for the catalytic domain of the
      endogenous 3-hydroxy-3-methylglutaryl coenzyme. A reductase, has been found to be
      effective for enhancing carotenoid levels in the yeast C. utilis.

PMID- 9519480
TI  - Extracellular particles of polymeric material formed in n-hexadecane fermentation
      by Pseudomonas aeruginosa.
AB  - In n-hexadecane fermentation by Pseudomonas aeruginosa, the production of
      rhamnolipids (biosurfactants) caused by nitrogen source limitation was observed
      during the stationary phase. The rhamnolipids caused severe foaming in the
      process, particularly at higher pH (ca. > 6.8). To reduce the foaming, several
      runs were made at a lower pH, i.e. 6.5 +/- 0.1. Some, however, behaved
      anomalously different. The rhamnolipid synthesis was very low. Instead, a large
      quantity of waxy particles with sizes up to 3-5 mm were formed. The waxy material
      was practically insoluble in all of the organic solvents tested, suggesting the
      cross-linked polymeric structure. A white, brittle solid was obtained after the
      material was thoroughly washed (with 0.05 M sodium bicarbonate, distilled water,
      and hexane) and vacuum-dried. Characterization of the washed material was made by
      Fourier-transformed infrared (FTIR) spectroscopy, thin-layer chromatography
      (TLC), and wet chemical analyses. It was found to contain less than 2.5% (w/w)
      proteins and less than 9% carbohydrates, of which only one sugar component was
      observed and tentatively identified as glucose by the TLC analysis. The material
      was, therefore, predominantly hydrocarbon-based, with oxidized functional groups
      such as esters, alcohols, and carboxylic acids being identified by FTIR. The
      lipase-catalyzed esterification of fatty acids and alcohols, within the oil
      droplets or at the oil/water interface of low local water activity, is postulated
      to play an important role in the waxy particle formation.

PMID- 9519481
TI  - Purification and characterisation of an intracellular X-prolyl-dipeptidyl
      aminopeptidase from Streptococcus thermophilus ACA-DC 4.
AB  - An intracellular X-prolyl-dipeptidyl aminopeptidase from Streptococcus
      thermophilus ACA-DC 4, isolated from traditional Greek yoghurt, was purified by
      anion exchange and gel filtration chromatography. A single band of molecular
      weight of about 80,000 appeared in SDS-PAGE; by gel filtration it was shown that
      the native enzyme was dimeric. The peptidase showed optimum activity on glycyl
      prolyl 4-nitroanilide at pH 7.0 and at 50 degrees C, with K(m) = 3.1 mM and Vmax
      = 3500 U mg-1; over 50 degrees C the enzyme activity declined rapidly. It was
      inactivated by PMSF; sulfhydryl group reagents and metal chelators had little
      effect on enzyme activity.

PMID- 9519483
TI  - The US prohibition experiment: myths, history and implications.

PMID- 9519482
TI  - An improved colony-PCR method for filamentous fungi for amplification of PCR
      fragments of several kilobases.
AB  - A method was developed to perform PCR directly on mycelial pellets or colonies
      treated with NOVOzym 234. The method allows rapid screening of large numbers of
      transformants of both sporulating and non-sporulating fungi for the presence of
      (co)transforming plasmid copies or for specific genetic modifications such as
      gene disruption and site specific integration. PCR fragments of at least 3.2 kb
      can be obtained. Using this method the identification of specific disruption
      mutants from Aspergillus niger and Beauveria bassiana was carried out.

PMID- 9519484
TI  - Behavioural alcohol research: new directions or more of the same?
AB  - AIM: Despite a large body of literature, a substantial burden of illness related
      to the abuse of alcohol, as well as significant economic and social costs,
      persist. As such, a critical examination of the type of research being published
      in relation to alcohol misuse seems appropriate, particularly since some experts
      in the field have expressed the view that the current distribution of research
      types may not be optimal. FINDINGS: The types of research conducted in two
      separate years, 1983 and 1993, were examined critically. Generally, the types of
      research conducted in both years was found to be similar: the majority of
      published alcohol research is behavioural, the majority of published behavioural
      alcohol research is descriptive and the majority of published behavioural
      intervention alcohol research represents tertiary prevention studies. Although
      the reasons for this distribution of research types are undoubtedly numerous and
      complex, some possible explanations are discussed. CONCLUSIONS: Overall, it is
      concluded that the current approach to alcohol research may have engendered a
      distribution of research types which is somewhat less than ideal and that, as
      such, a new approach may be indicated. Some strategies that may assist in
      redressing the perceived imbalance are considered.

PMID- 9519485
TI  - Research into smoking or nicotine and human cognitive performance: does the
      source of funding make a difference?
AB  - AIMS: To establish whether there is a relationship between tobacco industry
      support of basic research and the conclusions drawn by the authors of that
      research. DESIGN: A sample of 91 papers investigating the effects of tobacco or
      nicotine use upon cognitive performance was analyzed to see if the pattern of
      conclusions drawn by researchers acknowledging tobacco industry support differed
      from the pattern of conclusions drawn by researchers not acknowledging tobacco
      industry support. FINDINGS: Scientists acknowledging tobacco industry support
      reported typically that nicotine or smoking improved cognitive performance while
      researchers not reporting the financial support of the tobacco industry were more
      nearly split on their conclusions. CONCLUSIONS: While it is only possible to
      speculate on the possible reasons, the existence of a possible bias in the
      published literature according to funding source must be given serious
      consideration.

PMID- 9519486
TI  - Tobacco health warnings and smoking-related cognitions and behaviours.
AB  - AIMS: To explore whether the introduction onto cigarette packs of new larger,
      more prominent health warnings in black on white would lead to an increase in:
      noticing warnings, thoughts about the effects of smoking, and consequent
      behaviours of not smoking a planned cigarette and/or prematurely stubbing out one
      already lit. In addition evidence was sought linking these effect to smoking
      cessation. DESIGN: Two national cross-sectional surveys of broadly representative
      samples of smokers: one about 2 weeks before the mandated introduction date of
      the warnings, and a follow-up 6 months later, part-way through implementation. A
      longitudinal subsample of smokers from the initial baseline survey was resurveyed
      at follow-up. SETTING: In Australia, new health warnings and strengthened
      contents labelling of cigarette packets were mandated for cigarettes manufactured
      from 1 January 1995. PARTICIPANTS: Broadly representative samples of Australian
      smokers: 510 at baseline, and 512 at follow-up. Two hundred and forty-three of
      the baseline sample were also resurveyed. MEASUREMENTS: Self-report on effects of
      warnings and smoking cessation activity. FINDINGS: In the cross-sectional sample
      at follow-up, 66% of smokers reported at least sometimes noticing the health
      warnings when taking out a cigarette (compared with 37% at baseline), and 14%
      reported they had refrained from smoking on at least one occasion as a result
      (compared with 7% at baseline). Not smoking as a result of noticing the (old)
      warnings at baseline was predictive of quitting at follow-up. Frequency of
      stubbing out cigarettes before they were finished as a result of thinking about
      smoking-related harm was not affected by the new warnings, but was predictive of
      making quit attempts. CONCLUSIONS: The new health warnings were more potent at
      stimulating both thoughts about negative effects of smoking and the appropriate
      consequent action of not smoking the planned cigarette. This is important as
      spontaneous rejection of cigarettes predicted subsequent cessation.

PMID- 9519487
TI  - Is crack cheaper than (powder) cocaine?
AB  - AIMS: To compare the prices of cocaine powder and crack cocaine in the United
      States. DESIGN: Retail prices for crack and powder cocaine are compared for 14 US
      cities between 1986 and 1991 using regression analysis and t-tests. MEASUREMENTS:
      Prices are estimated from the United States Drug Enforcement Administration's
      System to Retrieve Information from Drug Evidence (STRIDE) database. FINDINGS: On
      average, crack is neither more nor less expensive per pure unit than powder
      cocaine. Prices are not equal in every city in every year, but crack is equally
      likely to be more or less expensive, and the differences are not large relative
      to variation in prices of both forms of cocaine between cities and over time.
      CONCLUSIONS: Crack has been widely believed to be cheaper than powder cocaine,
      and this "fact" has been used to help explain why US drug problems worsened in
      the 1980s. However, crack is not, in fact, cheaper per pure unit than powder
      cocaine. Other explanations must be sought for why crack spread so rapidly
      relative to powder cocaine.

PMID- 9519488
TI  - Patterns of symptom complaints in methadone maintenance patients.
AB  - AIM: Not all maintenance patients respond to methadone in the same manner, and
      many complain of withdrawal symptoms during the 24-hour inter-dosing interval
      (i.e. the dose does not 'hold'). The persistence of these complaints are a source
      of concern as they may signal unsanctioned drug use and poor treatment outcome.
      This study examined the prevalence and profile of symptom complaints in methadone
      maintenance patients who report that their methadone dose does not 'hold'.
      DESIGN: In the first phase, a cross-sectional survey of 114 methadone patients
      examined a range of symptoms including direct opioid effects and withdrawal.
      Phase 2 involved a comparison of the temporal pattern of symptom complaints
      between patients who reported the oral dose not 'holding' and those who did not.
      SETTING: Participants in this study were enrolled in the South Australian Public
      Methadone Maintenance Program. MEASUREMENTS: In Phase 1, a checklist of 21
      commonly reported symptom complaints associated with methadone maintenance
      treatment was administered. In Phase 2, this checklist was modified to include
      only those symptoms that changed in the 24-hour inter-dosing interval. The
      checklist was administered eight times over this period. Further data were
      collected using the Morphine Benzedrine Group Scale of the Addiction Research
      Centre Inventory, a measure of positive opioid effect. FINDINGS: In Phase 1, it
      was found that approximately one-third of the sample reported that the methadone
      dose was consistently inadequate in preventing withdrawal symptoms for the entire
      inter-dosing interval. They could not be differentiated by demographic, health,
      other drug use or treatment characteristics. In Phase 2, despite having a higher
      oral methadone dose, patients reporting that their daily dose did not 'hold'
      experienced a smaller degree of opioid effect, and a greater intensity of opioid
      withdrawal, during the 24-hour period. CONCLUSION: These data demonstrate that
      there is a change in pharmacodynamic response over the 24-hour period for all
      methadone patients, but the degree of change is greater in a subgroup of
      patients. Charting symptom presentation throughout the inter-dosing interval can
      aid in identifying those patients who are experiencing difficulties with their
      treatment regime.

PMID- 9519489
TI  - Young and recent-onset injecting drug users are at higher risk for HIV.
AB  - AIMS: To determine whether young or recent-onset injecting drug users (IDUs) are
      at increased risk of HIV infection, and to compare trends in risk behaviours and
      HIV incidence among subgroups of IDUs. DESIGN: Associations of age and onset of
      injecting with HIV prevalence and injecting risk behaviours were determined among
      current IDUs who entered an Amsterdam cohort between 1989 and 1995, and compared
      with current IDUs recruited in two street surveys in 1990 and 1993. In the
      cohort, trends from 1986 through 1995 in injecting risk behaviour (as reported at
      entry) and in HIV seroconversion (among current IDUs during follow-up) were
      determined using logistic and Poisson regression. FINDINGS: Sizable portions of
      IDUs were young (< or = 25 years: 14-30%) or had recently started injecting
      (within the last 3 years: 17-21%). Between 37% and 50% of young IDUs recently
      started injecting. HIV prevalence was 12-24% among young IDUs, and 5-12% among
      recent-onset IDUs. Young IDUs more often reported current borrowing than older
      IDUs. Borrowing declined significantly in all subgroups, except young IDUs. The
      crude HIV incidence declined from 18/100 person-years (PY) in 1986 to 5/100 PY in
      1995. Trends in HIV incidence were not significantly different for subgroups of
      age or onset of injecting. In a multivariate analysis, recent onset of injecting
      was an independent predictor (p = 0.04) for HIV seroconversion, but age was not
      (p = 0.68). CONCLUSIONS: Important proportions of drug users are young or have
      recently started injecting. HIV prevalence is relatively high among young and
      recent-onset IDUs. Recent onset of injection is an independent predictor for HIV
      seroconversion. Our observations may be explained by non-random patterns of
      borrowing used needles/syringes. Recent-onset IDUs should be approached more
      actively for HIV counselling and testing.

PMID- 9519490
TI  - Planned duration of residential drug abuse treatment: efficacy versus
      effectiveness.
AB  - AIMS: Two randomized controlled trials of residential drug abuse treatment
      programs found the programs to be equally effective, based on outcomes among
      those assigned to the treatments. This study aimed to compare the relative
      efficacy of the programs, based on outcomes among those who received the specific
      treatment program as planned. DESIGN: Secondary analyses of data from two
      concurrent randomized controlled trials, with stratification by actual length of
      stay. SETTING: Two residential drug abuse treatment facilities in the United
      States. PARTICIPANTS: Six hundred and twenty-eight clients were enrolled over a 2
      year period, representing 85% of all clients admitted, 91% of all eligible
      clients, and 95% of those asked to participate. INTERVENTIONS: At one facility,
      clients were randomized to 3-month or 6-month versions of a traditional
      therapeutic community program. At the second facility, clients were randomized to
      3-month or 6-month versions of a modified therapeutic community program that
      emphasized relapse prevention and health education. MEASUREMENTS: Time from
      admission to first drug use (except alcohol); and Addiction Severity Index (ASI)
      composite scores for severity of drug, alcohol, legal, and employment problems.
      FINDINGS: Five hundred and thirty-nine clients (86%) completed a follow-up
      interview at least 16.5 months after admission. In the relapse prevention trial,
      benefits of the 6-month program were generally limited to those who stayed at
      least 40 days. In the therapeutic community trial, among those who stayed at
      least 171 days, the 12-month program had a beneficial effect on employment.
      Otherwise, there were inconsistent differences between the 6- and 12-month
      programs. CONCLUSIONS: On average, clients who stayed in treatment at least 80
      days benefited from continuing in treatment for up to 6 months, but not beyond.
      Conversely, those admitted to programs of longer planned duration who dropped out
      of treatment early had worse outcomes than those who dropped out of shorter
      programs. Thus, although longer planned duration of treatment may be efficacious,
      it is not effective.

PMID- 9519491
TI  - Toward a stepped care approach to treating problem drinkers: the predictive
      utility of within-treatment variables and therapist prognostic ratings.
AB  - AIMS: Cost containment, a central issue in current health planning, encourages
      the use of brief interventions. Although brief interventions for problem drinkers
      have proved successful, a portion of such individuals do not change their alcohol
      use during treatment. DESIGN: Repeated measures design (pre-treatment, within
      treatment and 6 months post-treatment). SETTING AND PARTICIPANTS: To identify
      individuals at risk for continued problem drinking, predictors of post-treatment
      drinking were examined for 212 problem drinkers who presented for treatment in an
      outpatient treatment clinic. INTERVENTION: All participants completed a brief
      cognitive behavioral motivational intervention. MEASUREMENTS: At the pre
      treatment assessment demographic, drinking pattern, severity of dependence and
      other cognitive variables (e.g. self-efficacy, goal choice) were collected.
      Within-treatment, drinking pattern and cognitive variables such as self-efficacy
      and goal choice were again measured. FINDINGS: Regression analyses showed that
      therapist prognosis ratings contributed significantly to the prediction of
      outcome even when pre-treatment variables were controlled. However, when within
      treatment variables were included in the prediction, variables such as within
      treatment drinking eliminated the predictive utility of therapist prognosis
      ratings. This pattern held for both percentage of days abstinent and drinks per
      drinking day at a 6-month follow-up. CONCLUSIONS: It is suggested that a stepped
      care approach based on prediction models that include clients' within-treatment
      response can be applied to the treatment of problem drinkers who show little
      initial response to treatment.

PMID- 9519492
TI  - The social costs of alcohol abuse in New Zealand.
AB  - AIMS: This study updates and extends previous New Zealand research on the social
      costs of alcohol abuse. DESIGN: This economic cost study used the human capital
      approach. SETTING: New Zealand, 1991. PARTICIPANTS: The total New Zealand
      population. MEASUREMENTS: The estimated cost of alcohol abuse for 1 year included
      direct and indirect costs. Costs such as lost production resulting from premature
      death and sickness, reduced working efficiency and excess unemployment comprised
      indirect costs. Direct costs included hospital costs, accident compensation
      payments, police and justice system costs. A range of social cost estimates was
      constructed based on various prevalence rates of alcohol abuse, discount rates
      for lost production and the excess unemployment rate. FINDINGS: Using a range of
      assumptions regarding the proportion of each event attributable to alcohol, the
      sum of social costs ranged from $1045 million to $4005 million in 1991. The
      direct costs ranged from $341 million to $589 million, respectively. CONCLUSIONS:
      While providing an indication of the societal impact of alcohol abuse, these
      costs pertain to a relatively narrow range of alcohol-related effects. The paper
      identifies a number of areas where further research is required.

PMID- 9519493
TI  - Interpersonal factors and post-treatment drinking and subjective wellbeing.
AB  - AIMS: A conceptual clarification of the domain of social relationships defines
      three aspects of social relationships (structure, function and quality), which
      have both alcohol-specific and general components. We analyse the correlations
      among post-treatment indicators of social relationships and the association
      between these interpersonal variables and post-treatment drinking and subjective
      wellbeing. DESIGN: This is a secondary analysis of data from an alcohol treatment
      outcome study, in which subjects were randomly assigned to one of three treatment
      conditions and followed for 18 months. SETTING: The outpatient treatment program
      is located within a private psychiatric hospital in the north-eastern United
      States. PARTICIPANTS: We analyzed the 140 subjects who completed a social network
      instrument 12 months following treatment assignment. INTERVENTION: This secondary
      analysis combined clients from three treatment conditions, all of which were
      based upon social learning theory. MEASUREMENTS: Interview and questionnaire self
      report data were collected by trained interviewers. FINDINGS: Indicators of
      social relationships are found to be relatively independent of one another. Only
      alcohol-specific social relationship indicators are significantly associated with
      drinking outcomes, and only general indicators are significantly associated with
      subjective wellbeing. Functional indicators, addressing social interaction
      content, have stronger effects on outcomes than structural or quality indicators.
      General and alcohol-specific support from friends have more influence than
      support from family; both surpass the influence of co-workers. CONCLUSIONS: A
      better understanding of the roles of social relationships during the course of
      treatment and recovery or relapse may help clarify how treatment personnel can
      utilize clients' interpersonal relationships more effectively to maximize
      treatment effectiveness.

PMID- 9519494
TI  - The effect of changes in alcohol consumption on mortality and admissions with
      alcohol-related diagnoses in Stockholm County--a time series analysis.
AB  - AIM: To study the effect of changes in per capita alcohol sales and indicators of
      alcoholism treatment on admissions to inpatient care and mortality for liver
      cirrhosis and alcoholism, alcohol intoxication and alcohol psychosis (AAA).
      DESIGN: Bivariate and multivariate time series analyses was conducted by applying
      the ARIMA-modelling technique. SETTING AND PARTICIPANTS: All analyses were
      conducted on quarterly data from Stockholm County 1980-94 with a population of
      1.7 million people. MEASUREMENTS: Data on sales of alcohol and disulfiram/calcium
      carbimide were used as input variables. Inpatient data (from the Stockholm
      Inpatient Care Register) and mortality data (from the Cause of Death Register) on
      all cases with alcoholism, alcohol psychosis and alcohol intoxication (AAA) and
      liver cirrhosis as underlying or contributory diagnoses were used as output
      variables. FINDINGS: Alcohol sales affected the cirrhosis rate. For cirrhosis
      mortality, but not for cirrhosis admissions, the effect was not only direct but
      also distributed over time. Significant direct and time lag effects of alcohol
      sales on both AAA series and cirrhosis admissions were found only during earlier,
      shorter periods, e.g. 1980-90. All four output series showed significant effects
      of sales of disulfiram/calcium carbimide and were the only significant predictors
      for the two AAA endpoints for the whole study period. CONCLUSIONS: These results
      suggest that to reduce the rate of alcohol-related problems caused by socially
      deteriorated and severely alcohol-dependent subjects (i.e. AAA), reduction of
      overall consumption should be complemented by treatment of alcohol-dependent
      subjects.

PMID- 9519495
TI  - Acamprosate treatment in a long-term community-based alcohol rehabilitation
      programme.
AB  - AIMS: To evaluate the efficacy of acamprosate in maintaining abstinence in weaned
      alcohol-dependent patients. DESIGN: A multicentre, double-blind, randomized
      control trial. Patients were individually randomly allocated to active or placebo
      conditions. Abstinence was assessed during a 6-month treatment period and after a
      6-month follow-up period. SETTING: A community-based, outpatient alcohol
      rehabilitation programme. PARTICIPANTS: Two hundred and forty-six alcohol
      dependent patients between the ages of 18 and 65 years were recruited immediately
      following acute, inpatient withdrawal treatment. MEASUREMENTS: The primary
      outcome measure was self-reported abstinence from alcohol since the previous
      sessions at 3, 6, 9 and 12 months following the start of treatment, with
      treatment taking place for a period of 6 months. FINDINGS: A significantly higher
      proportion of patients in the acamprosate group were abstinent after 3 months and
      6 months of treatment. The percentage of patients with continuous abstinence at
      the end of the treatment period was almost double for the acamprosate group than
      for the placebo group (40.7% vs. 20.8%, respectively). Acamprosate significantly
      increased the retention of patients in the treatment programme. Six months after
      drug treatment ceased, the criterion of abstinence since the previous visit was
      reached by significantly more patients from the acamprosate group (43.4%) than
      from the placebo group (29.8%), but this difference was not statistically
      significant at the 3-month point after cessation of study medication.
      CONCLUSIONS: Acamprosate may be a useful pharmacological compound for the long
      term treatment of alcohol-dependence when applied in a community-based
      rehabilitation programme.

PMID- 9519496
TI  - Assessing the relationship between maternal cocaine use and abruptio placentae.
AB  - Abruptio placentae during pregnancy can result in significant morbidity and
      mortality to both mother and infant. A comprehensive literature search of
      publications from 1966 to April 1995 identified 11 studies on the association
      between maternal cocaine use and abruptio placentae. Their results were combined
      in a meta-analysis. The pooled odds ratio for abruptio placentae and maternal
      cocaine use was 3.92 (95% confidence interval 2.77-5.46). The strength and
      consistency of the association, its biological plausibility and the results of
      experimental studies in animals all suggest that cocaine use during pregnancy
      causes abruptio placentae.

PMID- 9519497
TI  - Maternal cannabis use and birth weight: a meta-analysis.
AB  - AIMS: To estimate the effect of maternal cannabis use on birth weight. DESIGN:
      Meta-analysis of published observational studies adjusted for cigarette smoking.
      Separate analyses were performed for studies of low birth weight and mean birth
      weight. We used fixed and random effects models, but in all cases the results
      were identical. SETTING: From the Medline database, we identified 10 studies in
      which the results were adjusted for cigarette smoking. In seven studies,
      information on cannabis use was collected prenatally. Five studies reported
      results for differences in mean birth weight associated with maternal cannabis
      use. PARTICIPANTS: 32,483 women giving birth to live-born infants. MEASUREMENTS:
      Mean birth weight and odds ratio for low birth weight. FINDINGS: Three analyses
      of the studies on mean birth weight were conducted to avoid double-counting women
      from one study. The largest reduction in mean birth weight for any cannabis use
      during pregnancy was 48 g (95% confidence interval (CI) 83-14 g), with
      considerable heterogeneity among the five studies. Mean birth weight was
      increased by 62 g (95% CI 8 g reduction-132 g increase; p heterogeneity 0.59)
      among infrequent users (< or = weekly) whereas cannabis use at least four times
      per week had a 131 g reduction in mean birth weight (95% CI 52-209 g reduction; p
      heterogeneity 0.25). From the five studies of low birth weight, the pooled odds
      ratio for any use was 1.09 (95% CI 0.94-1.27, p heterogeneity 0.19). CONCLUSIONS:
      There is inadequate evidence that cannabis, at the amount typically consumed by
      pregnant women, causes low birth weight.

PMID- 9519498
TI  - Maternal cocaine use and low birth weight newborns: a meta-analysis.
AB  - AIM/DESIGN: Many epidemiological studies published on the association between
      maternal cocaine/crack use and birth weight have either lacked precision or
      failed to control for major confounding, predominantly by tobacco smoking. Meta
      analysis enables a single summary measure of effect to be calculated by combining
      data from any number of individual studies, thus enhancing statistical power. We
      undertook a number of meta-analyses using only studies that had adjusted for
      tobacco smoking to estimate more precisely the effect of maternal cocaine use on
      birth weight. FINDINGS: A meta-analysis of five studies presenting data for 'any'
      prenatal cocaine exposure, adjusted for tobacco smoking but unadjusted for
      gestational age, produced a pooled relative risk estimate from a fixed effects
      analysis of 2.15 (95% CI 1.75-2.64). However, there was substantial heterogeneity
      among studies (p < 0.001), and the relative risk from a random effects analysis
      was smaller (1.65) with a confidence interval that included unity (95% CI 0.94
      2.83). Addition of a further study adjusted for gestational age had minimal
      effect on the pooled estimate: the fixed effects relative risk was 2.14 (1.77
      2.60) and the random effects estimate 1.77 (1.15-2.71). When data on more intense
      prenatal exposure were analysed, the fixed and random effects analysis produced
      the same pooled estimate of the relative risk of 4.42 (2.24-8.71), suggesting
      that more frequent cocaine exposure was associated with a higher relative risk
      for low birth weight. Data from studies on mean reduction in birth weight
      produced a pooled estimate of 112 g (95% CI 62-161 g). CONCLUSIONS: The current
      study suggests that maternal cocaine use causes low birth weight, and that the
      effect is greater with heavier use. However, despite the adjustment for tobacco
      and the adjustment by some studies for other confounders such as race, maternal
      age, gravidity and socio-economic status, it could be argued that other life
      style factors not controlled for may account for the observed effects. While this
      argument is not supported by some other types of study, the issue of residual
      confounding can only be finally addressed by analytical studies which adequately
      control for important variables.

PMID- 9519499
TI  - The relationship between maternal use of heroin and methadone and infant birth
      weight.
AB  - AIMS/DESIGN: Reduction in mean birth weight and increased incidence of low birth
      weight are both associated with exposure to illicit heroin in pregnancy. Many
      studies examining neonatal outcomes in pregnant heroin users treated with
      methadone report improvements in birth weight. As a consequence, methadone
      treatment has become the 'gold standard' for the management of the pregnant
      heroin user. However, not all studies report significant birth weight increases
      associated with methadone. We undertook a number of meta-analyses on reduction in
      mean birth weight and incidence of low birth weight to estimate more precisely
      the effect of illicit heroin and methadone. FINDINGS: Results showed mean
      reduction in birth weight associated with heroin use: 489 g (95% CI 284-693 g),
      compared with methadone: 279 g (229-328 g). Similarly, the pooled relative risk
      estimate for low birth weight for maternal heroin use was 4.61 (95% CI 2.78
      7.65), compared with 1.36 (0.83-2.22) for methadone. Analysis of data on combined
      heroin and methadone use produced a pooled mean reduction in birth weight of 557
      g (403-710 g), with a pooled relative risk estimate for low birth weight of 3.28
      (2.47-4.39). Pooling 'any' methadone data, regardless of heroin use, produced an
      estimated reduction in birth weight of 395 g (311-478 g) and a relative risk
      estimate for low birth weight of 1.90 (1.29-2.81). Combining all data in an 'any'
      opiate use analysis also produced a mean reduction in birth weight of 483 g (386
      583 g) and a relative risk estimate for low birth weight of 3.81 (2.57-5.65).
      CONCLUSIONS: The current findings suggest that heroin use while receiving
      methadone may counteract the birth weight advantage gained from methadone alone.
      Whether this is due to fetal exposure to heroin plus methadone, to reduced
      antenatal care, other behavioural and environmental factors associated with
      concurrent use of heroin and methadone or a combination of these is unclear.
      Nevertheless, these results challenge the current belief that the pregnant user
      is always better off receiving methadone than not, and suggests that methadone
      may not be the appropriate treatment for the pregnant women who continue to use
      illicit heroin.

PMID- 9519500
TI  - Prevalence of coronary calcification in relation to age, gender and risk factor
      profile in the insight population.
AB  - Calcium controls numerous events within the vessel wall. Permeability of the
      endothelium is calcium dependent. Calcium is also essential for penetration of
      low-density lipoprotein particles through the endothelium as well as the
      monocytes that travel through the subendothelial space. Other calcium-dependent
      processes include platelet activation and adhesion, vascular smooth muscle
      proliferation and migration, and synthesis of fibrous connective tissue in the
      subendothelial space. Current evidence indicates that calcium channel blockers
      retard the development of atherosclerosis in monkeys and rabbits. Human trials
      have evaluated sequential coronary angiograms in patients undergoing coronary
      angiography for symptomatic coronary artery disease. Double helix computerised
      tomography is a non-invasive technique that can detect, measure and compare
      calcification in the coronary arteries. Our objectives are to determine whether
      the use of nifedipine vs diuretics in hypertensive patients at high risk of
      coronary calcification will arrest or slow the progression of calcification in
      the coronary arteries, and to assess the effect of the two drugs on left
      ventricular hypertrophy, and left ventricular mass as well as on changes in left
      ventricular function.

PMID- 9519501
TI  - Monotherapy with nifedipine GITS compared with atenolol in stable angina
      pectoris. The Working Group on Cardiovascular Research (WCN).
AB  - This double-blind, randomised multicentre study compares nifedipine
      gastrointestinal therapeutic system (GITS) with atenolol in 129 male patients,
      with exercise-induced angina pectoris. At 4 weeks, there was no significant
      difference between nifedipine GITS 60 mg o.d. and atenolol 100 mg o.d., in
      respect of improved time to onset of 0.1 mV ST-segment depression, time to onset
      of pain, and total exercise time. Atenolol, but not nifedipine, significantly
      reduced heart rate and systolic blood pressure at rest and during exercise. There
      were significantly more vasodilator-related side effects with nifedipine.
      Nifedipine GITS and atenolol as once-daily monotherapy are equally effective and
      safe, but have different effects on exercise parameters.

PMID- 9519503
TI  - Pharmacological and therapeutic basis for combined administration of beta
      blockers and calcium channel blockers in the treatment of stable chronic angina.
AB  - Pharmacodynamics of beta-adrenergic blockers and dihydropyridines are potentially
      synergic in the treatment of angina pectoris. The anti-ischaemic effect of beta
      blockers is mainly the consequence of reductions in heart rate and inotropism,
      while DHPs promote afterload reduction and coronary vasodilation. Furthermore,
      beta blockers antagonise the possible dihydropyridines-induced reflex sympathetic
      activation. Despite these mechanistic considerations the results of clinical
      trials are not homogeneous. Differences in the assessment of the beta blocker
      dihydropyridines connection are due to differences in trial design, dosage and
      formulation of both dihydropyridines and beta-blockers, and in baseline
      characteristics of the study population. The predominant finding is that a
      combination of a dihydropyridines and a beta blocker is not superior to either
      drug alone as a first step treatment of unselected patients with stable or
      unstable angina. In contrast, combination therapy is often efficacious when
      residual ischaemia is present under dihydropyridines or beta blocker monotherapy.
      That this combination is usually well tolerated thus appears to represent a
      useful treatment of severe angina pectoris. Combination of a non-dihydropyridines
      calcium antagonist such as diltiazem or verapamil with a beta blocker offers
      similar synergistic anti-ischaemic effects, but the addition of their negative
      chronotropic action may lead to severe bradycardia and thus limit its usefulness,
      especially in elderly patients with conduction disturbances.

PMID- 9519504
TI  - Action: a 30,000 patient-years double-blind, placebo-controlled trial of
      nifedipine GITS in stable angina. ACTION Research Group.
AB  - To assess the overall balance between efficacy and safety of the long-action
      calcium antagonist nifedipine gastrointestinal therapeutic system (GITS) in
      patients with stable symptomatic coronary artery disease (CAD), a large
      multicentre placebo-controlled double-blind trial called ACTION has been mounted
      (A Coronary Disease Trial Investigating Outcome with Nifedipine GITS). Patients
      are eligible if they have proven CAD on antianginal treatment in stable clinical
      condition for at least 3 months without heart failure. The left ventricular
      ejection fraction must be above 40%. Patients not already on lipid-lowering
      therapy will be evaluated and such treatment will be started based on current
      guidelines before randomisation. After washout of an already given calcium
      antagonist, more than 6000 patients in total will be randomised in equal
      proportions to either nifedipine GITS 60 mg once daily or placebo. The mean
      clinical follow-up will be 5 years, with no restrictions on concomitant
      medication (with the exception of digitalis, calcium antagonists and class III
      antiarrhythmics). The primary end-point will be survival free of major
      cardiovascular events (i.e. survival free of acute myocardial infarction,
      emergency coronary angiography, overt heart failure, stroke and peripheral
      revascularisation). The study has 95% power to detect a significant (p < 0.05)
      18% improvement of this end-point and is of sufficient size to exclude an excess
      mortality of 3.1 per 1000 patient-years. In this first stable angina trial of
      this size and scope, 185 centres in Canada, Europe, Israel, Australia and New
      Zealand will participate. Recruitment will start in November 1996 and is planned
      to be completed in 2 years.

PMID- 9519505
TI  - Nifedipine GITS versus diltiazem in chronic stable angina: a randomised
      multicentre study.
AB  - In order to compare the efficacy of nifedipine gastrointestinal therapeutic
      system (GITS) with diltiazem, 99 patients with chronic stable angina were studied
      in a parallel-group randomised trial. According to the results of the two
      exercise tolerance tests (ETTs) performed during the placebo run-in, patients
      were divided into a fixed threshold group if the variability in time to 1 mm ST
      segment depression was 20%, or a variable threshold group if it was higher.
      Efficacy was assessed by comparing the time to 1 mm ST-depression on a bicycle
      ETT after 4 weeks of treatment, adjusting for the baseline value. The adjusted
      means were 7.44 min for nifedipine GITS and 7.68 min for diltiazem; the
      difference was -0.24 min, with a lower 90% confidence limit of -0.90, which is
      within the stated interval for equivalence. The same result was confirmed by the
      'intention-to-treat' analysis, and comparable results were obtained both in fixed
      and in variable threshold groups. The incidence of side effects was 12% with
      nifedipine GITS and 8.2% with diltiazem. Nifedipine GITS and diltiazem were found
      to be equally effective in increasing exercise tolerance in chronic stable angina
      patients.

PMID- 9519506
TI  - CFCS and the ozone layer.
AB  - Ozone is an important constituent of the atmosphere. Ozone forms a distinct layer
      in the lower stratosphere known as the ozone layer. The ozone layer acts as a
      fragile shield because it protects man and other life forms from exposure to
      harmful short-wavelength ultraviolet (UV) radiation. The agents, particularly
      chemical, which affect the amount of ozone present in the atmosphere have been a
      source of concern for more than 20 years. This has been reinforced by the
      dramatic decline of stratospheric ozone levels first measured in Antarctica and
      now apparent worldwide. The combination of routine measurements of ozone
      depletion, careful laboratory studies and mathematical modelling of ozone in the
      atmosphere, has demonstrated that the reactive fragments produced when
      chlorofluorocarbons (CFCs), halons and other halogenated compounds break down in
      the stratosphere are responsible for the ozone loss. As CFCs have widespread and
      sometimes apparently essential uses in modern society, there has been an intense
      effort to develop safe, effective replacements which have a negligible or much
      smaller impact on the environment. The Montreal Protocol, signed by over 140
      nations, has been implemented to control and phase out the chemical compounds
      responsible for ozone loss.

PMID- 9519507
TI  - The biological effects of ozone depletion.
AB  - Thinning of the ozone layer is predicted to result in increased levels of
      ultraviolet (UV) B radiation at the earth's surface. This effect has been
      confirmed by measurements made in relatively unpolluted areas such as Antarctica,
      the southern part of South America and at mid-to-high latitudes in the northern
      hemisphere. It has been harder to show in populated northern latitudes because of
      a number of confounding factors, notably weather systems and low level ozone
      pollution. Although UVB forms only a small proportion of the UV spectrum it has
      potent biological effects so that a small increase in penetration of UVB to the
      earth's surface has profound effects on a wide range of life forms. Most
      attention has been paid to the effects of an increase in UVB on human health,
      particularly the effects on skin cancer, resistance to infectious diseases and
      cataract formation. However, the effects of increased levels of UVB on other
      parts of the ecosystem, particularly on the primary producers in aquatic and
      terrestrial food chains, may be of even.

PMID- 9519508
TI  - Metered dose inhalers: current and future uses.
AB  - Respiratory disease poses an enormous burden on individuals and society. Asthma
      and chronic obstructive pulmonary disease (COPD), the diseases discussed here,
      contribute towards a substantial proportion of ill health and cost to the NHS and
      the economy. Most health professionals consider the inhaled route to be the best
      method of delivering drugs to the respiratory system. Four types of inhaled
      delivery system are in use: pressurised metered dose inhalers (pMDIs); dry powder
      devices; pMDIs and large volume spacers in combination; and nebulisers. In the UK
      pMDIs are the cheapest type of device on the market and are usually the method of
      choice for those patients able to use them. International agreement to phase out
      CFCs has led to the development of alternative propellants for pMDIs. The role of
      pMDIs is predicted to increase in the future. Demand for pMDIs to treat asthma is
      likely to increase as the introduction of clinical guidelines extends best
      practice, and their use to treat patients with COPD is increasing. Novel drugs
      for the respiratory system, including gene therapy and drugs for non-respiratory
      disorders, may well employ pMDIs as a delivery system in the future.

PMID- 9519509
TI  - The technical transition to CFC-free inhalers.
AB  - Pressurised metered dose inhalers (pMDIs) provide essential therapy for a large
      proportion of the 70 million people in the world affected by asthma. However,
      current pMDIs contain chlorofluorocarbons (CFCs) and will have to be phased out.
      Several classes of propellants have been considered as alternatives to CFCs and
      the pharmaceutical industry has taken forward two hydrofluoroalkanes (HFA)--HFA
      134a and HFA-227--for development in non-CFC pMDIs. The development of non-CFC
      pMDIs to date has resulted in the worldwide introduction of a salbutamol pMDI
      (with a HFA-134a propellant) which is identical both in vitro and in vivo to CFC
      pMDIs. The beclomethasone pMDI under development has superior lung deposition and
      much reduced oropharyngeal deposition compared with the CFC pMDI, with the
      potential for significant benefits for patients.

PMID- 9519510
TI  - The transition in practice: policy makers and purchasers.
AB  - The transition to CFC-free pressurised metered dose inhalers (pMDIs) is not
      optional and cannot be ignored. The UK Government intends that CFCs will be
      removed from all medicinal products by the end of 1999. An overall strategy is
      needed to guide health professionals and patients through the transition process.
      Collaborative working between the pharmaceutical industry, health authorities and
      relevant health professionals is essential to ensure a smooth transition with
      minimal disruption to patients. The factors that need to be taken into
      consideration for a smooth transition and the role of national and local drivers
      in this process are outlined. The main focus around change must be on patients'
      confidence in their medication.

PMID- 9519511
TI  - The transition in practice: health professionals and patients.
AB  - The transition to CFC-free pressurised metered dose inhalers (pMDIs) raises
      issues for health professionals and patients. Health professionals need to be
      aware of any differences between old and reformulated products. The currently
      available reformulated salbutamol is equivalent to the old product so no dosage
      adjustment is implicated in the changeover. Available information on the new
      reformulated steroids suggests significantly smaller doses may be required for
      some reformulations as a result of improved drug deposition. This should not pose
      a problem if health professionals follow current asthma guidelines and titrate
      treatment against effect. Patients must be well prepared for transition, be aware
      of key facts about the new formulation and be aware of the reason their physician
      recommends change. The likelihood of a seamless transition to the new inhalers
      will be enhanced if health professionals coordinate the transition in a planned
      way in each district.

PMID- 9519512
TI  - Making sense of health needs assessment.

PMID- 9519513
TI  - Nurse practitioners in general practice--an inevitable progression?

PMID- 9519514
TI  - An evaluation of a nurse-led ear care service in primary care: benefits and
      costs.
AB  - BACKGROUND: Nurses trained in ear care provide a new model for the provision of
      services in general practice, with the aim of cost-effective treatment of minor
      ear and hearing problems that affect well-being and quality of life. AIM: To
      compare a prospective observational cohort study measuring health outcomes and
      resource use for patients with ear or hearing problems treated by nurses trained
      in ear care with similar patients treated by standard practice. METHOD: A total
      of 438 Rotherham and 196 Barnsley patients aged 16 years or over received two
      self-completion questionnaires: questionnaire 1 (Q1) on the day of consultation
      and questionnaire 2 (Q2) after three weeks. Primary measured outcomes were
      changes in discomfort and pain; secondary outcomes included the effect on normal
      life, health status, patient satisfaction, and resources used. RESULTS: After
      adjusting for differences at Q1, by Q2 there was no statistical evidence of a
      difference in discomfort and pain reduction, or differential change in health
      status between areas. Satisfaction with treatment was significantly higher (P =
      0.0001) in Rotherham (91%) than in Barnsley (82%). Average total general
      practitioner (GP) consultations were lower in Rotherham at 0.4 per patient with
      an average cost of 6.28 Pounds compared with Barnsley at 1.4 per patient and an
      average cost of 22.53 Pounds (P = 0.04). Barnsley GPs prescribed more drugs per
      case (6% of total costs compared with 1.5%) and used more systemic antibiotics (P
      = 0.001). CONCLUSIONS: Nurses trained in ear care reduce costs, GP workload, and
      the use of systemic antibiotics, while increasing patient satisfaction with care.
      With understanding and support from GPs, such nurses are an example of how
      expanded nursing roles bring benefits to general practice. Nurses trained in ear
      care reduce treatment costs, reduce the use of antibiotics, educate patients in
      ear care, increase patient satisfaction, and raise ear awareness.

PMID- 9519515
TI  - The general practitioner, the drug misuser, and the alcohol misuser: major
      differences in general practitioner activity, therapeutic commitment, and 'shared
      care' proposals.
AB  - BACKGROUND: The primary care setting has been regarded in government policy and
      the scientific literature as an ideal setting for the work needed to meet the
      Health of the Nation drug and alcohol targets. Although studies have pointed to
      the negative attitudes held by general practitioners (GPs) towards alcohol- and
      drug-misusing patients, there has been no direct comparison of the work and
      attitudes of the GP towards these patients. AIM: To compare the work and
      attitudes of GPs towards alcohol- and drug-misusing patients. METHOD: All GPs in
      an outer London area (157 doctors) were surveyed, using an eight-page postal
      questionnaire, collecting clinical and attitudinal data alongside demographics
      and practice information. A response rate of 52% was achieved. RESULTS: General
      practitioners reported working with only 3.5 patients drinking above recommended
      guidelines in the previous four working weeks, and even fewer drug-using patients
      (0.75). While they viewed the alcohol-misusing patients negatively, the drug
      misuser elicited substantially more negative attitudes. The primary care setting
      was seen as appropriate to work with the alcohol-misusing patient but not with
      drug users. Training and support from local services would encourage
      substantially more GPs to work with alcohol misusers but not with drug misusers.
      CONCLUSIONS: Our findings indicate that there are some cautious grounds for
      optimism that GPs are willing to work with alcohol misusers; however, with regard
      to drug misusers, we find a GP workforce that is only minimally involved with
      this group and would not be greatly encouraged by the provision of additional
      training, support, or incentives. The Health of the Nation targets are not being
      met, and GPs are not detecting adequate numbers of the patients at whom these
      targets are aimed. Emphasis has been placed on the role of primary care, but the
      real achievements that can be made require detection of the less severe drinkers
      and injecting drug misusers.

PMID- 9519516
TI  - Barriers to preventive care in general practice: the role of organizational and
      attitudinal factors.
AB  - BACKGROUND: There are numerous barriers to preventive care. In this paper we
      focus on barriers related to the organization of preventive services and to the
      general practitioners' (GPs') attitudes and self-efficacy expectations. The
      prevention of cardiovascular disease was taken as a case study. AIM: To study the
      organization of cardiovascular services and the attitudes and self-efficacy
      expectations of GPs, the relationships that exist between these factors, and the
      influence of practice and provider characteristics. METHOD: A survey was
      conducted among 95 general practices with 195 GPs. RESULTS: Few practices were
      sufficiently well-organized to provide effective preventive services. Seventy per
      cent of the GPs had positive self-efficacy expectations. Thirty to fifty per cent
      had positive attitudes. Few relationships were found between the organization of
      services and positive attitudes or expectations. Moreover, few relationships were
      found between practice and provider characteristics and barriers studied. List
      size played some role in the presence of barriers. CONCLUSION: Barriers to
      prevention exist. Even a positive attitude or self-efficacy expectation does not
      automatically coincide with a practice organization equipped for prevention.
      Changing attitudes is probably not enough. Efforts have to be directed at the
      organization of services.

PMID- 9519517
TI  - Teenagers' views on the general practice consultation and provision of
      contraception. The Adolescent Working Group.
AB  - BACKGROUND: The rate of unwanted pregnancies in adolescents in the United Kingdom
      (UK) is one of the highest in Europe and is a major reason for the RCGP's concern
      at the under-use of general practitioners' (GPs') contraceptive services by young
      people. AIM: To discover the attitudes of 15- to 16-year-olds to the GP
      consultation and contraceptive services. METHOD: Questionnaires were completed as
      part of an evaluation of a novel sex education programme in 30 schools in 1994,
      and provided the data for this study. A total of 4481 teenagers (51.6% male and
      48.4% female completed the questionnaires in their classrooms under conditions of
      complete confidentiality. RESULTS: The median consulting rate per year was two
      for males and three for females. Over 60% of adolescents attended the
      consultation with a parent. Of the males, 27.5% 'felt that the discussion with
      their GP could be relayed to their parents against their wishes', as did 25.1% of
      the females. Other difficulties with GP appointments were identified as
      embarrassment (63% of females and 46% of males), difficulty getting a quick
      appointment (44% of both males and females), and an unsympathetic GP (32% of
      females and 20.5% of males). CONCLUSIONS: Adolescents identify significant
      factors blocking them from easy access to consultation with their GP. These
      included lack of trust in confidentiality, lack of staff friendliness, and delay
      in appointment. Consideration of how these blocks can be removed will assist in
      providing improved contraceptive services in primary care. General practices need
      to consider the above factors when providing contraceptive and other services to
      their teenage patients.

PMID- 9519518
TI  - Reducing reconsultations for acute lower respiratory tract illness with an
      information leaflet: a randomized controlled study of patients in primary care.
AB  - BACKGROUND: General practitioners (GPs) prescribe antibiotics to three-quarters
      of patients who consult with a lower respiratory tract illness (LRTi). In spite
      of this management, around a quarter of patients reconsult for the same symptoms
      within a month. AIM: To investigate the impact of providing a simple leaflet
      regarding the natural history of lower respiratory tract symptoms on
      reconsultation rates for previously well adults presenting to their GP with an
      LRTi. METHOD: Seventy-six GPs studied 1014 previously well adults presenting with
      an illness defined as an LRTi. Management was left to the GP's discretion. Half
      of the patients were randomly allocated to receive an information leaflet at the
      end of the consultation, blinded from the GP. The endpoint was reconsultation for
      the same symptoms within one month. RESULTS: Follow-up data was available for
      1006 adults, of whom 182 (18%) reconsulted. Fewer patients who received the
      leaflet (75/505; 14.9%) returned to the surgery compared with those who did not
      (107/501; 21.4%; P = 0.007). The same benefit was found for the 723 (72%) adults
      treated initially with antibiotics; 16% (60/369) in the leaflet group returned
      compared with 23% (81/354) in the no leaflet group (P = 0.02). CONCLUSION:
      Informing previously well patients about the natural history of LRTi symptoms is
      an effective strategy for reducing reconsultations, benefiting the patient and
      the GP; it is likely to reduce antibiotic prescriptions and future patient
      consultation habits.

PMID- 9519519
TI  - Scottish general practice registrars--their views on psychotherapy training.
AB  - BACKGROUND: Psychological problems constitute between 10% and 30% of general
      practice workload. In 1993, the Royal Colleges of General Practitioners and
      Psychiatrists published guidelines on the psychiatric component of vocational
      training for general practice, recognizing the need for training in the
      psychological aspects of patient care and knowledge of the psychotherapies.
      Little is known as to how much these guidelines have been followed. AIM: To
      determine Scottish general practice registrars' views on whether the above
      training objectives had been met. METHOD: An anonymous self-report questionnaire
      was sent to all general practice registrars in west and south-east Scotland one
      month before the end of their trainee year with a 95% response rate. This
      provided basic descriptive information on the population surveyed and their
      attitudes to psychotherapy training. RESULTS: Altogether, 53% had spent time in
      psychiatry and half of these had had access to a consultant psychotherapist, but
      only 9% had been involved in using a psychological approach to treatment. A total
      of 51% disagreed that they had had enough psychotherapy experience, and 44% did
      not feel confident in assessing patients for psychotherapy, 15% saying that lack
      of knowledge would prevent them from referring patients. Of the whole sample, 88%
      felt that further psychotherapy training would be helpful. CONCLUSION: The
      majority of general practice registrars in Scotland did not feel that training
      objectives had been met regarding the attainment of skills in the
      psychotherapies.

PMID- 9519520
TI  - A survey of infertility practices in primary care in Scotland.
AB  - An 83% response rate was obtained to a postal questionnaire survey of general
      practitioners (GPs) carried out as part of a national infertility audit in
      Scotland. This provided information about how GPs are managing infertility and
      their opinions on 12 suggested criteria for good practice in a primary care
      setting.

PMID- 9519521
TI  - Clinical guidelines and the management of hypertension: a between-practice and
      guideline comparison.
AB  - It has previously been demonstrated that individual general practitioners (GPs)
      diagnose and treat at different levels of blood pressure and according to
      different risk factor profiles. This study sought to examine the variation in the
      achievement of control of hypertension in a sample of 20 treated hypertensive
      patients in 18 UK general practices. There was a marked between-practice
      variation in the percentage of patients with controlled hypertension. Practices
      appear to apply different hypertension guidelines to patients consistently, with
      significant correlations across practices in seven out of ten possible guideline
      combinations. There remains marked variation in the management of hypertension
      between different general practices in the UK. Factors other than recommendations
      in guidelines appear to be responsible for this variation.

PMID- 9519523
TI  - A systematic review of empirical research into ethics in general practice.
AB  - Much of the bioethical literature addresses the problems of tertiary medicine,
      with little attention to the daily concerns of general practitioners (GPs). The
      present review assesses the current state of research into the range and nature
      of ethical issues for GPs, looking specifically at the content of the research,
      the methods employed, and the philosophical framework of the research. A
      systematic search of MEDLINE, CINAHL, and Sociofile identified nine articles
      which form the basis for this review. The majority of the research reviewed here
      is quantitative in nature, using hypothetical cases with closed questions and
      categorical responses. No consistently significant variables were identified.
      Decisions appear to be inconsistent in terms of theoretical models and moral
      psychology. Ethical issues of concern to GPs differed from those commonly
      reported in the bioethical literature. There is a paucity of research into the
      ethical concerns of general practice. The existing body of research is
      quantitative in nature, leaving many unanswered questions concerning the reasons
      behind the decisions of GPs. There is a need for qualitative studies to further
      our understanding of this area.

PMID- 9519522
TI  - Are patients who present late with cancer registered with low referring
      practices?
AB  - This study examines whether a clinical outcome (stage of breast or bowel cancer
      at referral) was related to variations in GP referral rates. A multivariate
      analysis of breast and bowel cancer patients referred from 183 Nottinghamshire
      practices during 1993 showed no adverse outcome associated with low GP referral
      rates. Variables included in the analysis were total and surgical referral rates,
      fundholding status, UPA(8) score of the practice, partnership size, and age and
      sex of the referred patient.

PMID- 9519524
TI  - Communication about risk--dilemmas for general practitioners. The Department of
      General Practice Working Group, University of Wales College of Medicine.
AB  - Measures of risk frequently contribute to our understanding, prevention, or
      treatment of disease, but it is important that general practitioners (GPs)
      explain clinical risks effectively to patients to ensure they are not
      misunderstood, as risk information can assist in decision-making processes and
      encourage behavioural change. However, the interpretation of risks by patients
      and doctors varies. It is argued that problems arise because communication about
      risk is usually framed in terms of the language of chance or probability. In this
      paper, we describe how probability theory developed, and suggest that attempts to
      communicate empirical risk processes in probabilistic language are bound to
      produce dilemmas. We explore how the theory relates to clinical practice and
      identify key issues that doctors must address in discussing risk with individual
      patients.

PMID- 9519525
TI  - Effective audit in general practice: a method for systematically developing audit
      protocols containing evidence-based review criteria.
AB  - Though many general practitioners (GPs) now take part in audit, there is still
      concern about the extent to which participation in audit leads to improvements in
      practice. Improved methods are needed for the incorporation of research evidence
      into criteria for use in audit. In this paper, a six-stage systematic method is
      described for developing audit protocols containing prioritized evidence-based
      criteria. The stages are: selection of a topic, identification of key elements of
      care, focused literature reviews, prioritization of the criteria on the strength
      of the evidence and impact on outcome, preparation of full documentation, and
      peer review.

PMID- 9519526
TI  - Oral anticoagulation monitoring.

PMID- 9519527
TI  - Oral anticoagulation monitoring.

PMID- 9519528
TI  - Evidence-based medicine.

PMID- 9519529
TI  - Evidence-based medicine.

PMID- 9519530
TI  - Evidence-based medicine.

PMID- 9519531
TI  - Evidence-based medicine.

PMID- 9519532
TI  - Hospital admissions and quality of chronic illness care.

PMID- 9519533
TI  - Summative assessment.

PMID- 9519534
TI  - Aspirin therapy for cardiovascular disease.

PMID- 9519535
TI  - Screening for diabetes.

PMID- 9519536
TI  - Screening for diabetes.

PMID- 9519537
TI  - Screening for diabetes.

PMID- 9519538
TI  - Death and the general practitioner.

PMID- 9519539
TI  - Low back pain services.

PMID- 9519540
TI  - Digital image cross-correlation technique for bite mark investigations.

PMID- 9519541
TI  - Solid-phase extraction of benzhexol from blood and urine.

PMID- 9519542
TI  - A computerised method for calculating the probability of pedigrees from genetic
      data.

PMID- 9519544
TI  - Effect of palmitoylcarnitine on the cellular differentiation, proliferation and
      protein kinase C activity in neuroblastoma nb-2a cells.
AB  - Palmitoylcarnitine is synthesized through the action of palmitoylcarnitine
      transferase I--an enzyme specifically inhibited by etomoxir. An increase of the
      intracellular content of palmitoylcarnitine in neuroblastoma NB-2a cells after
      administration of carnitine was correlated with an inhibition of cell
      proliferation and a concomitant promotion of differentiation processes. The
      activity of protein kinase C was measured in vivo, with cells permeabilized
      through the use of streptolysin O and a peptide substrate. Palmitoylcarnitine
      inhibited the phorbol ester stimulated reaction of the peptide phosphorylation in
      a concentration dependent way. The degree of protein kinase C inhibition was
      correlated with intracellular increase of the palmitoylcarnitine content,
      pointing to this compound as a natural modulator of protein kinase C activity.

PMID- 9519543
TI  - Solvent residues in cocaine and heroin.

PMID- 9519545
TI  - Acute lead toxicity and energy metabolism in rat brain synaptosomes.
AB  - Although the neurotoxic effects of lead (Pb) are well documented, the subcellular
      mechanisms of its action in the central nervous system are not fully understood.
      The present work examined some parameters of energy metabolism in nerve endings
      of the brains of adult rats exposed to Pb. We applied the model of acute Pb
      toxicity in vivo, imitating the acute action of lead observed in occupationally
      exposed workers or in occasional incidents of poisoning. The measurement of Pb
      levels in the synaptosomal fraction exhibited its significant accumulation under
      applied conditions. Oxygen consumption increased in synaptosomes from Pb-treated
      rats whereas the activity of cytochrome c oxidase did not change. The
      intrasynaptosomal levels of ATP and CrP were significantly elevated, as was the
      activity of creatine kinase, suggesting the activation of the CrP/CK system. On
      the other hand, the activity of the synaptosomal Na+,K(+)-ATP-ase decreased. We
      suggest that under acute Pb toxicity conditions the mobilization of CrP/CK system
      may take place to protect the cell against the effects of decreased Na+,K(+)-ATP
      ase activity.

PMID- 9519546
TI  - Nitro-l-arginine attenuates SKF 38393-induced oral activity in neonatal 6
      hydroxydopamine-lesioned rats.
AB  - Nitric oxide (NO) in brain has been implicated in neuronal regulatory processes
      and in neuropathologies. Previously we showed that NO modified quinpirole-induced
      yawning, a behavioral measure of dopamine (DA) D3 receptor activation in rats.
      The aim of this study was to characterize the effect of nitro-L-arginine methyl
      ester HCl (NAME) and L-arginine HCl on reactivity of rats to the DA D1 receptor
      agonist SKF 38393 and DA D1 antagonist SCH 23390 in intact and neonatal 6
      hydroxydopamine (6-OHDA)-lesioned rats (134 micrograms of base ICV at 3rd day
      after birth). L-arginine HCl (300 mg/kg i.p.) increased the oral activity
      response in 6-OHDA-lesioned rats, like SKF 38393, and induced catalepsy in intact
      control rats, like SCH 23390. In contrast, NAME had no effect on oral activity or
      catalepsy, but fully attenuated SKF 38393-induced oral activity. These findings
      indicate that L-arginine HCl has no apparent effect at the DA D1 receptor, but
      that NAME is effective in attenuating a DA D1 agonist-induced effect.
      Consequently NO may be an intracellular second messenger for supersensitized
      receptors associated with DA D1 agonist-induced oral activity.

PMID- 9519547
TI  - Diversity of connections of the temporal neocortex with amygdaloid nuclei in the
      dog (Canis familiaris).
AB  - Reciprocal connections of amygdaloid nuclei with the temporal neocortex in the
      dog were investigated. Injections of fluorescent tracers and BDA into particular
      temporal areas were made in eleven dogs. The topographical arrangement of
      connections and variations in their density differentiate the temporal neocortex
      in the dog into a few regions. Among them, the cortex involving the anterior part
      of the ectosylvian gyrus did not send any amygdalopetal projection. The middle
      ectosylvian, dorsal zone of the posterior ectosylvian and the anterior part of
      the Sylvian gyrus were weakly connected with the amygdala. The cortical region
      involving the ventral zone of the posterior ectosylvian and composite posterior
      areas, as well as posterior Sylvian gyrus, was characterized by profuse
      connections with the amygdaloid complex. Cortico-amygdaloid connections originate
      in the wide cortical area of the auditory cortex of the middle and dorsal part of
      the posterior ectosylvian gyrus as well as in the auditory association cortex
      located in the ventral ectosylvian, composite posterior and posterior Sylvian
      gyri. The connections showed a dorso-ventral gradient of increasing density, in
      the direction of association fields. The most substantial projection taking rise
      from the ectosylvian posterior and posterior composite gyri terminated
      preferentially in the pericapsular sector of the lateral amygdaloid nucleus and,
      to a lesser degree, in its medial sector. Terminals of connections originating in
      the Sylvian gyrus occupied preferentially the intermediate part of the lateral
      nucleus, slightly more medially than that from the ectosylvian and posterior
      composite areas. Additionally, axonal terminals derived from the composite
      posterior and Sylvian posterior areas were observed in the basal parvocellular
      and magnocellular nuclei. Neocortical projections were reciprocated by
      amygdalofugal connections with two exceptions: the basal magnocellular nucleus
      was distinguished by a substantial amygdalofugal projection to the temporal
      neocortex focused on the dorsal Sylvian gyrus, and the central nucleus of the
      amygdala, in contrast, received an exclusively corticofugal projection.

PMID- 9519549
TI  - Reversal of visual discrimination and visual acute extinction in cats with poor
      or limited early visual experience.
AB  - Transformation of visual instrumental conditioned reflexes rewarded with food was
      compared in cats binocularly deprived of pattern vision in the early period of
      life (BD cats), control cats reared also in the laboratory but with open eyes (C
      cats) and cats reared in normal environment (N cats). In Expt. I the cats were
      given 4 sequential reversal trainings of cross vs. disc discrimination and in
      Expt. II a response to a gate marked with a cross or a disc was submitted to 4
      sequential acute extinctions and restorations. The results show that both visual
      deprivation and rearing in monotonous laboratory environment moderately affect
      transformation of associations between visual stimuli and hunger drive and
      instrumental responses. However, in BD cats transformation learning is less
      impaired than previously studied visual discrimination learning.

PMID- 9519548
TI  - Effect of acoustic stimulus characteristics on the startle response in hooded
      rats.
AB  - The acoustic startle response (ASR) depends on stimulus parameters such as
      duration, intensity and particularly on the stimulus rise time. The aim of our
      study was to determine to what extent the ASR parameters are affected by the
      spectral characteristics of the stimulus. Therefore, in this experiment the
      amplitude and the latency of the acoustic startle reflex were assessed for a
      fixed pulse duration and for a variety of stimulus frequencies ranging between 3
      and 23 kHz. The ASRs were studied in 11 adult hooded rats exposed to 2-ms (120 dB
      SPL) tone pulses of different frequencies presented in random order, with or
      without 70 dB white noise background. Statistical analysis of the data revealed
      significant differences between ASR amplitudes for different frequencies. In our
      experimental situation the rats responded more readily to a low frequency
      stimulus. The startle amplitude decreased with tonal frequencies and
      distinguishable difference were seen for 3, 7, and 10 kHz pulses. However, such
      differences were not readily observed for higher frequencies i.e. 15, 20, 23 kHz.
      The same pattern of differences was observed when the acoustic stimulus was
      presented with the white noise background. The observed differences may be
      attributed, firstly, to a spectral characteristic of the stimulus and thus to an
      audibility in rats and secondly to a behavioral meaning of a stimulus of a
      different frequency.

PMID- 9519550
TI  - Interaction of sulfhydryl reagents with K+ transport in adrenal chromaffin
      granules.
AB  - In the present study the functional role of SH groups in the Ca(2+)-independent
      K(+)-selective channel activity in the membrane of bovine adrenal gland
      chromaffin granules has been studied. Ionic channel activity has been estimated
      using 86Rb+, a K+ analogue, flux measurements. The inhibition of chromaffin
      granules K+ channel by SH modifying agents, such as N-ethylmaleimide, mersalyl
      and phenylarsenoxide, is described.

PMID- 9519551
TI  - Phosphorylation of 68 kDa neurofilament proteins has no significant effect on
      their assembly.
AB  - Native low molecular weight neurofilaments (NF-L) from bovine spinal cord with
      original phosphate content of 0.4 moles of phosphate per 1 mol of protein were
      phosphorylated with cyclic AMP dependent protein kinase and protein kinase C. In
      a similar way recombinant mouse NF-L proteins which did not contain any phosphate
      were phosphorylated with the same enzymes in both, the assembled and disassembled
      forms. The final phosphate content in both types of NF-L proteins reached about 4
      moles of phosphate per 1 mol of protein. This phosphorylation had no effect on
      the assembly of NF-L into filaments as observed by electron microscopy.

PMID- 9519552
TI  - Changes in the central respiratory rhythm following pharmacological blockade of
      the nucleus parabrachialis medialis in the rabbit.
AB  - Experiments were performed in halothane-anesthetized, paralyzed, bilaterally
      vagotomized and artificially ventilated rabbits. Arterial blood pressure,
      expiratory carbon dioxide concentration, and electrical activity of the right
      phrenic nerve were recorded prior to and after xylocaine microinjection to the
      left nucleus parabrachialis medialis (NPBM). The location of the xylocaine
      blockade was verified histologically. It was found that blockade of the NPBM
      results in a decelerated respiratory rhythm due to lengthening of both phases of
      the respiratory cycle. These results do not corroborate the role of NPBM in the
      regulation of respiration as postulated by Bertrand and Hugelin (1971).

PMID- 9519553
TI  - The method of training dogs in auditory recognition memory tasks with trial
      unique stimuli.
AB  - Three adults dogs were trained in a auditory recognition delayed-matching-to
      sample (DMS) task. The experimental setting consisted of one central speaker
      located in front of the dogs head, two side speakers with nearby response pedals
      and one rotary food delivery system. Three hundred twenty natural sounds were
      used as trial-unique stimuli. Sample stimuli were always given through the
      central speaker. After the delay of 1.5 s, both sample and testing stimuli were
      activated alternately through the two side speakers. Bar-press response toward
      the sample stimulus was rewarded by food. The DMS training was continued until
      attaining a criterion 90% correct responses in 90 consecutive trials. After a
      control pause, the dogs were retrained to the criterion, and then they were given
      performance tasks with delays extended to 10-, 30-, 60- and finally to 90-s, in
      blocks of 90 trials. Dogs required about 1,000 trials of auditory recognition
      memory training in order to reach the criterion. Their behavior was also stable
      after the control pause. The dogs performance declined gradually with extended
      delays reaching an average of 63.4% for the delay of 90 s. Results indicate that
      the DMS task with auditory stimuli alternating during the testing stage of trial,
      is a promising method for testing auditory recognition memory.

PMID- 9519554
TI  - Sphingosine modulates Ca2+ signals via phospholipase C dependent pathway in
      glioma C6 cells.

PMID- 9519555
TI  - NAS-NRC Twin Registry Survey. National Academy of Sciences--National Research
      Council.

PMID- 9519557
TI  - Monogenic models of obesity.
AB  - The study of rodent monogenic models of obesity has yielded significant insights
      into the pathogenesis of obesity. Multiple independent mutations in several genes
      can produce obesity. As these genes act in different regulatory pathways, it is
      clear that multiple mechanisms can produce obesity. Furthermore, a single gene
      defect can produce regulatory deficits in multiple modes of energy expenditure.
      The most severe forms of genetic obesity involve multiple pathogenic processes.
      It is significant that regulatory defects in any single component of caloric
      intake or energy expenditure appear to be sufficient to produce obesity. Finally,
      the systems regulating energy balance are loosely coupled; positive and negative
      influences are not completely balanced, both in strength as well as temporally.

PMID- 9519558
TI  - Genetic dissection of obesity in polygenic animal models.
AB  - In contrast to diseases caused by single-gene defects, many of the most common
      human maladies such as obesity, atherosclerosis, diabetes, and hypertension
      exhibit continuous phenotypic variation and a predominantly multifactorial and
      polygenic basis. Genes with roles in energy balance, nutrient partitioning, lipid
      and insulin metabolism, and a variety of behavioral traits are likely interacting
      with environmental stimuli to regulate obesity phenotypes. With the current
      proliferation of highly polymorphic genetic markers and the refinement of
      experimental approaches, it is now possible to screen thoroughly the genomes of
      model organisms for the individual genes or quantitative trait loci (QTL) that
      control measurable polygenic traits such as obesity. With the growing wealth of
      comparative mapping, it will be possible to predict the location of a homologous
      locus in the human after first mapping it in the mouse. Many experiments have
      been conducted in mice, rats, and pigs to estimate the number, location, and
      effect of QTL controlling obesity and related traits. This review describes the
      design and strategies of such studies and summarizes the results and their
      implications toward understanding the complex nature of obesity in humans.

PMID- 9519559
TI  - Prader-Willi and other syndromes associated with obesity and mental retardation.
AB  - Constitutional obesity and mental retardation cooccur in several multiple
      congenital anomaly syndromes, including Prader-Willi syndrome, Bardet-Biedl
      syndrome, Cohen syndrome, Albright hereditary osteodystrophy, and Borjeson
      Forssman-Lehmann syndrome as well as some rarer disorders. Although hypothalamic
      pituitary axis abnormalities are thought to be a possible causative mechanism in
      some of these disorders, current knowledge is insufficient to explain the
      pathophysiologic mechanism of obesity in most multiple congenital anomaly/mental
      retardation syndromes. The chromosomal location of many of these syndromes is
      known, and studies are ongoing to identify the causative genes. Further
      delineation of the functions of the underlying genes will likely be instructive
      regarding mechanisms of appetite, satiety, and obesity in the general population.
      This review details current knowledge of the clinical and molecular genetic
      findings of multiple congenital anomaly/mental retardation syndromes associated
      with intrinsic obesity in an effort to delineate causative mechanisms and genetic
      abnormalities contributing to obesity.

PMID- 9519560
TI  - Genetic and environmental factors in relative body weight and human adiposity.
AB  - We review the literature on the familial resemblance of body mass index (BMI) and
      other adiposity measures and find strikingly convergent results for a variety of
      relationships. Results from twin studies suggest that genetic factors explain 50
      to 90% of the variance in BMI. Family studies generally report estimates of
      parent-offspring and sibling correlations in agreement with heritabilities of 20
      to 80%. Data from adoption studies are consistent with genetic factors accounting
      for 20 to 60% of the variation in BMI. Based on data from more than 25,000 twin
      pairs and 50,000 biological and adoptive family members, the weighted mean
      correlations are .74 for MZ twins, .32 for DZ twins, .25 for siblings, .19 for
      parent-offspring pairs, .06 for adoptive relatives, and .12 for spouses.
      Advantages and disadvantages of twin, family, and adoption studies are reviewed.
      Data from the Virginia 30,000, including twins and their parents, siblings,
      spouses, and children, were analyzed using a structural equation model (Stealth)
      which estimates additive and dominance genetic variance, cultural transmission,
      assortative mating, nonparental shared environment, and special twin and MZ twin
      environmental variance. Genetic factors explained 67% of the variance in males
      and females, of which half is due to dominance. A small proportion of the genetic
      variance was attributed to the consequences of assortative mating. The remainder
      of the variance is accounted for by unique environmental factors, of which 7% is
      correlated across twins. No evidence was found for a special MZ twin environment,
      thereby supporting the equal environment assumption. These results are consistent
      with other studies in suggesting that genetic factors play a significant role in
      the causes of individual differences in relative body weight and human adiposity.

PMID- 9519561
TI  - The genetics of obesity: what have genetic studies told us about the environment.
AB  - Genetic studies have shown that both childhood and adult body mass index are
      substantially heritable. The evidence for shared family environmental influences
      is largely absent, even though there are clear indications that secular changes
      in energy expenditure have brought about a significant increase in the prevalence
      of obesity. This apparent inconsistency may be explained by the dual phenomena of
      the near-universality of access to environments that facilitate reductions in
      energy expenditure (e.g., TV as a recreational pastime), together with heritable
      individual differences in the response to or utilization of these environments.
      The impact of changes in nonshared environments on body weight can be estimated
      from biometrical genetical studies and is found to be both small and relatively
      short-lived. Genetic and environmental results from longitudinal studies are
      consistent with what is known about the changing distribution of adiposity during
      adulthood and clinical experience of the difficulty of maintaining behavioral
      induced weight loss.

PMID- 9519562
TI  - Summary of human linkage and association studies.
AB  - It is now widely accepted that genes play a significant role in the development
      of human obesity. The mapping of genes contributing to obesity and to regional
      fat distribution in humans is based on association and linkage studies. This
      article presents a review of these studies in humans for phenotypes related to
      excess body mass or body fat and regional fat distribution. The various obesity
      phenotypes are first defined followed by a brief description of the linkage and
      association methods. The early association studies based on red blood cell
      genetic polymorphisms are reviewed and the studies which have reported
      significant evidence of linkage and association described. Studies with negative
      findings are not reviewed. Results of these studies suggest a total of 28 genes
      or chromosomal regions that may be associated and/or linked with body fat and fat
      distribution phenotypes in human. With genomewide searches for obesity genes
      actually under way, together with the 16,000 genes and transcripts included in
      the recent human gene map, this number is likely to increase rapidly in the next
      few years.

PMID- 9519564
TI  - Genetic influences on human energy expenditure and substrate utilization.
AB  - Understanding the genetic factors of obesity requires consideration of the
      genetic basis of the underlying etiological factors including energy expenditure
      and substrate utilization. Genetic susceptibility studies suggest that altered
      energy expenditure and/or preferential substrate utilization are likely to be
      involved in the etiology of obesity. Twin and family studies suggest that there
      is a strongly heritable component to resting energy expenditure, substrate
      utilization, and the thermic response to feeding. Physical activity energy
      expenditure has been less well studied; new data are presented in young sib pairs
      that suggest moderate heritability of nonresting energy expenditure. Only a few
      candidate gene studies have been performed to examine the role of basic proteins
      involved in energy expenditure (the sodium-potassium ATPase and the uncoupling
      protein) or substrate utilization (fatty acid binding protein). The lack of
      information in this area warrants further investigation into genetic aspects of
      energy and substrate metabolism.

PMID- 9519565
TI  - Selected methodological issues in meiotic mapping of obesity genes in humans:
      issues of power and efficiency.
AB  - This paper focuses on methods for mapping novel obesity genes in humans via
      meiotic mapping techniques. By novel we mean genes that are as yet unidentified
      as playing a role in obesity. We begin by presenting a discussion of why we
      believe it is important to seek out novel obesity genes and, in particular, novel
      genes of small effect. In light of the arguably Herculean task of finding genes
      of small effect with conventional gene mapping methods, we discuss alternative
      methods and procedures that may enhance our ability to map novel obesity genes of
      small effect. Many of these methods have been discussed previously in the
      literature and are summarized here. These include reconceptualizing power in the
      context of genomewide scans, multivariate linkage approaches, the use of
      phenotypically extreme subjects, and the use of large sibships. These are
      discussed in the context of linkage studies. Association studies and
      disequilibrium mapping are also discussed, and again, issues involving the use of
      extreme phenotypes and multiple testing are included. We also provide a brief
      discussion of DNA pooling and transmission disequilibrium tests for quantitative
      traits. Finally, we advocate data pooling techniques (e.g., meta-analysis) to
      enhance the power and efficiency of the entire field of the genetics of obesity.

PMID- 9519563
TI  - Heritable variation in food preferences and their contribution to obesity.
AB  - What an animal chooses to eat can either induce or retard the development of
      obesity; this review summarizes what is known about the genetic determinants of
      nutrient selection and its impact on obesity in humans and rodents. The selection
      of macronutrients in the diet appears to be, in part, heritable. Genes that
      mediate the consumption of sweet-tasting carbohydrate sources have been mapped
      and are being isolated and characterized. Excessive dietary fat intake is
      strongly tied to obesity, and several studies suggest that a preference for fat
      and the resulting obesity are partially genetically determined. Identifying genes
      involved in the excess consumption of dietary fat will be an important key to our
      understanding of the genetic disposition toward common dietary obesity.

PMID- 9519566
TI  - Putting the behavior into the behavior genetics of obesity.
AB  - Tremendous advances in the genetic underpinnings of obesity have emerged in
      recent years. Curiously, behavioral genetic methods have provided relatively less
      information on the environmental influences and intermediary behaviors which
      promote human obesity. This situation in unfortunate since human obesity is, in
      part, environmentally determined and the result of behaviors such as eating and
      physical (in)activity. This article has several goals. First, it outlines reasons
      why behavior qua behavior should be a specific focus of obesity-oriented
      behavioral genetic designs. Second, possible explanations for why behavior has
      been underinvestigated are explored. Third, data regarding the genetic/
      environmental architecture of various obesity-related phenotypes (e.g., food
      intake, physical activity, etc.) are reviewed. Fourth, a commentary on the
      importance of gene-environment interactions is offered. Finally, suggestions for
      future research, including a list of possible "candidate environments" and
      "candidate intermediary behaviors," are offered.

PMID- 9519567
TI  - Seasonal prevalence of Anopheles dirus and malaria transmission in a forest
      fringed village of Assam, India.
AB  - Seasonal abundance of Anopheles dirus (s.l.) and malaria prevalence in an
      isolated forest fringed village was monitored at monthly intervals during August
      1995 to July 1996. An. dirus was the only vector species detected during the
      study period. Its density pattern showed distinct seasonality with the peak
      occurring in the month of July and very low number during cool dry months.
      Positive correlation (r = 0.721) was found between the density of An. dirus and
      the amount of rainfall occurring two weeks prior to the collections. Overall
      sporozoite rate of 1.6% and parous rate of 64.7% were found in the study. Malaria
      transmission closely followed the density pattern of An. dirus and was seasonal
      with slide positivity rate and P. falciparum percentage of 47 and 83%
      respectively. Mean malaria prevalence was higher (p < 0.05) in females.

PMID- 9519568
TI  - HCH and DDT residues in human and bovine milk at Hardwar, India.
AB  - Concentrations of HCH and DDT in human and bovine milk were determined in two
      areas under malaria control namely, BHEL, Hardwar with bioenvironmental control
      strategy and rural and urban areas of Bahadrabad PHC of Hardwar district with
      residual spraying of insecticides. Mean HCH and DDT residues in human milk in
      BHEL were 0.027 and 0.021 mg/kg, while from Bahadrabad were 0.089 and 0.149 mg/kg
      respectively. Similarly, mean HCH and DDT contents in bovine milk from BHEL were
      0.019 and 0.008 mg/kg, while 0.058 and 0.029 mg/kg, respectively from Bahadrabad.
      Statistically significant differences were recorded in HCH and DDT levels in
      human and bovine milk samples between BHEL and Bahadrabad areas of Hardwar
      district. The mean levels of HCH and DDT in bovine milk samples did not exceed
      the maximum residual limit of 0.05 mg/kg from BHEL whereas, 38.5% samples from
      Bahadrabad area exceeded this limit.

PMID- 9519569
TI  - Seasonality of indoor resting anophelines in stone quarry area of District
      Allahabad, U.P.
AB  - Alongitudinal study was conducted in four indicator villages of PHC Shankargarh,
      District Allahabad, U.P. from July 1991 to June 1992 to have information on
      seasonality of indoor resting anopheline species in silica sand/hard stone quarry
      area. Fourteen anopheline species namely, An. aconitus (0.35%), An. annularis
      (17.03%), An. barbirostris (0.09%), An. culicifacies (36.74%), An. fluviatilis
      (0.13%), An. nigerrimus (0.01%), An. pallidus (4.40%), An. splendidus (0.02%),
      An. stephensi (0.01%), An. subpictus (40.84%), An. tessellatus (0.15%), An.
      turkhudi (0.004%), An. vagus (0.20%) and An. varuna (0.02%) were collected. An.
      culicifacies, An. subpictus and An. annularis were found throughout the year. An.
      fluviatilis, An. pallidus, An. vagus and An. aconitus were also observed in all
      the seasons except extreme summer. However, An. barbirostris and An. splendidus
      were collected only in monsoon/post-monsoon and winter seasons. An. tessellatus
      and An. stephensi were recorded in winter and spring seasons. An. nigerrimus and
      An. varuna were recorded in winter, while An. turkhudi in spring. Prolonged high
      vector density may be attributed to the extended malaria transmission in this
      area.

PMID- 9519570
TI  - Geographical distribution and dramatic increases in incidences of malaria:
      consequences of the resettlement scheme in Gambela, SW Ethiopia.
AB  - The spatial distribution of malaria results from the interaction between vector,
      parasite, host, physical and human environments. This basic geographical approach
      provides an illustration of the geographical distribution of malaria in the
      world, particularly in the tropical regions. Due to the global climate change and
      population movements, it is predicted that malaria could have a greater impact on
      the non-immune or unprepared populations in the Northern Hemisphere in the coming
      decades. Presently, Sub-Saharan Africa (SSA) is the most adversely affected
      region in the world. Like any other SSA country, Ethiopia suffers from both
      epidemic (unstable) and endemic (stable) malaria in the high and lowland regions,
      respectively. Gambela is one of the areas with stable malaria in the humid
      tropical region of the country. This study is based on observations, unpublished
      data, interviews and discussions with settlers and officials in Gambela. It is
      found that a degree of diverse malaria prevalence is associated with altitudinal,
      temperature and rainfall variations. Owing to the settlement and land-use
      changes, unexpected rainfall patterns, temperature increase, unstable political
      system and poverty, malaria has gone beyond its geographical limits. As a result,
      the number of malaria affected people has increased in the last 12 years. It is
      suggested that proper physical and social planning, understanding the geography,
      entomology, epidemiology, behaviour and life-cycle of malaria parasite,
      cooperation between the policy-makers, malaria specialists, neighbouring
      countries and international communities are urgent, if malaria has to be
      controlled and eradicated.

PMID- 9519571
TI  - An epidemiological and entomological investigation on malaria outbreak at
      Tamulpur PHC, Assam.

PMID- 9519572
TI  - Incrimination of malaria vector on Ayodhya Hills, India.

PMID- 9519573
TI  - Marcella O'Grady Boveri (1863-1950): her three careers in biology.
AB  - The career of Marcella O'Grady Boveri (1863-1950), a nineteenth-century Catholic
      woman educated in biology at MIT and Bryn Mawr, is discussed both in the
      biological context of the times and with regard to the position of women in
      science. The thesis is that her life pattern differed strikingly from that of
      other woman biologists of her generation and that the character of her
      contributions to biology varied with that pattern. Perhaps it is in consequence
      that the significance of her considerable achievement has been hidden. Boveri's
      circumstances led her to collaboration rather than independence in research: she
      worked with skill and interest, but without formal recognition, on her husband's
      theoretically important and already established research program in Germany (1900
      1915). She thought it a privilege to do so. Earlier (1889-1896), at Vassar
      College, and later (1927-1943), at the newly established Albertus Magnus College,
      she was an innovator who introduced and developed new curricula in biology, a
      stimulating and influential teacher, a mentor, and a role model. In addition, she
      did much to promote international communication, as exemplified both by her
      English translation of Theodor Boveri's prescient theory of cancer and by her
      influence in bringing important scientists to the United States.

PMID- 9519574
TI  - Deception, efficiency, and random groups. Psychology and the gradual origination
      of the random group design.
AB  - In the life sciences, psychology, and large parts of the other social sciences,
      the ideal experiment is a comparative experiment with randomly composed
      experimental and control groups. Historians and practitioners of these sciences
      generally attribute the invention of this "random group design" to the
      statistician R.A. Fisher, who developed it in the 1930s for agricultural
      research. This essay argues that the random group design was advanced in
      psychology before Fisher introduced it in agriculture and that in this context it
      was the unplanned outcome of a lengthy historical process rather than the
      instantaneous creation of a single genius. The article analyzes how the random
      group design came about bit by bit when methodological practices from nineteenth
      century psychophysical laboratories were gradually adapted, extended, and
      codified by twentieth-century educational psychologists to support procedural
      objectivity in educational administration. In passing, the article also amends
      the received historiography of the separate elements of randomization and control
      groups.

PMID- 9519575
TI  - Interpreting published research: knowing what we know.

PMID- 9519576
TI  - Antecedents of sexual victimization: factors discriminating victims from
      nonvictims.
AB  - A sexual victimization survey was used to assess the factors that would
      discriminate between victims and nonvictims of sexual assault. The sample
      consisted of 241 female college students at a large midwestern university.
      Victimization status was ascertained from the 13-question Sexual Experiences
      Survey developed by Koss and Gidycz and Koss and Oros. Data eliciting information
      about possible associated factors (demographics, dating history, sexual history,
      personality characteristics and traits) and victimization status were obtained by
      adapting several scales and instruments into a single Dating and Relationship
      Survey. Of the 241 women, 102 reported they had been victimized. Discriminant
      function analysis was used to develop a set of variables that significantly
      identified victimization status. The variables found to be related to women's
      being sexually victimized were (a) number of different lifetime sexual partners,
      (b) provocative dress, and (c) alcohol use.

PMID- 9519578
TI  - Dieting behavior of Asian college women attending a US university.
AB  - Dieting behavior, body dissatisfaction, self-esteem, and food intake of 73 Asian
      women attending a US university were investigated and compared retrospectively
      with attitudes of 247 US-born female students at the same university. The Asian
      women reported restrained eating and body dissatisfaction only about half as
      often as the US women did. In both the Asian and US college women, body
      dissatisfaction scores were significantly correlated to body mass index and self
      esteem scores. Fourteen percent of the Asian women in the restrained eating/body
      dissatisfied group, and 40% of the US students in that group reported intentional
      vomiting for weight control. Some of the Asian international students practiced
      undesirable dieting behaviors and reported body dissatisfaction levels similar to
      those of many US college women. College health professionals should recognize
      that disordered eating among Asian women must not be overlooked because of
      stereotypical perceptions about Asian women's body size and type.

PMID- 9519579
TI  - Screening and chemoprophylaxis for tuberculosis infection in college populations.
AB  - Active tuberculosis and the potential for widespread disease exist on college
      campuses. To maximize the benefit and minimize the potential harm of a screening
      program, health service clinicians should administer tuberculin skin tests to
      high-risk students only. Those found to be infected should be considered for
      prophylactic treatment. The criteria that identify students as being at high risk
      need to be clearly appreciated, especially the issue of birth outside the United
      States. Certain countries of origin pose a high risk; others do not. By
      understanding the fundamentals of the current pandemic and employing a consistent
      approach, college health professionals can make the correct screening decisions,
      thereby reducing the risk to their campus communities and assisting in the
      eradication of this preventable disease.

PMID- 9519577
TI  - Understanding the three national databases on collegiate alcohol and drug use.
AB  - An overview of the three major databases used to examine alcohol and other drug
      use habits of American college students is provided. The databases are compared
      in terms of purpose, study population, subject selection, method of
      administration, focus, utility for institutional use, and trend analyses. The
      authors conclude that no one source of data is "best." Rather, the studies
      represent three different sources of data. Although information from these
      databases overlaps to some extent, each database makes a unique contribution to
      the field.

PMID- 9519580
TI  - Evaluation of an intervention to change attitudes toward date rape.
AB  - The prevalence of date rape among college students is a major concern. Although
      much research has been done on risk factors for date rape, few researchers have
      specifically described interventions for the various stages of developing a date
      rape prevention program. Previous programs have often relied on educational
      videos that feature a "typical" date-rape scenario, a format that some
      researchers suggest may have a negative effect on the way people engage in
      aggressive sexual behavior. A less violent theatrical production based on social
      learning theory and risk-factor reduction that resulted in a significant
      improvement in attitudes related to date rape among both male and female students
      at an elite Texas university is described.

PMID- 9519581
TI  - Hepatitis B immunization in a university student population.
AB  - In the United States, hepatitis B virus infection occurs predominantly among
      adolescents and young adults, despite the availability of an effective vaccine.
      Immunization status and hepatitis B virus (HBV) vaccine acceptance among 505
      students visiting the student health services of a large southern university were
      investigated. Only 58 students had received HBV vaccine. The cost of the vaccine
      was paid by the students personally (35.5%) or by their parents (34.5%) or
      employers (31.0%). Nearly half of the students (45.7%) did not know their
      vaccination status. Lower immunization percentages were found among Hispanics,
      men, persons of lower education levels, and students aged 25 years and under.
      Being immunized was related to the perception that the vaccine was affordable,
      although most students (95.7%) said that the cost of HBV vaccine was excessive.
      Health professionals' emphasis on the need for HBV vaccination and a reduction in
      the price of the vaccine could improve HBV immunization rates among university
      students.

PMID- 9519582
TI  - Preliminary normative data on DSM-IV attention deficit hyperactivity disorder in
      college students.
AB  - Identification of attention deficit hyperactivity disorder (ADHD) in adults
      presents a number of problems because there is no one specific diagnostic test
      for the condition. Given this challenge, clinicians often struggle between
      restrictive and exclusionary diagnostic methods or overinclusive acceptance that
      ADHD is a prevalent and disabling problem. A modified version of the Attention
      Deficit Hyperactivity Rating Scale was administered to 468 students at a large
      midwestern university. Analysis of the results suggested that the degree of ADHD
      symptoms in college students is modest and indicated that cutoff scores of 4 for
      current symptoms of inattention and hyperactivity-impulsivity would be sufficient
      to identify a college student as distinct from the norm. Although it would be
      premature to accept the calculated thresholds completely, clinicians should be
      aware of these differences when evaluating college students for ADHD.

PMID- 9519583
TI  - Weighing in college students' diet and exercise behaviors.
AB  - A questionnaire was used to investigate the nutritional health behaviors of 302
      college students at a large urban university. Body mass index (BMI) was
      calculated for each student, using self-reported heights and weights. Eight
      percent of the surveyed students were categorized as overweight on the basis of
      their BMIs. However, 50% of the students who were rated underweight on the basis
      of their BMIs classified themselves as overweight. Only 39% of the students
      reported exercising 3 or more times per week; 76% of the students reported that
      they ate the same foods day after day. Recommendations are presented for colleges
      and universities that are offering or are considering offering nutritional
      education programs for students.

PMID- 9519584
TI  - Linguistic cues in the acquisition of number words.
AB  - Previous research has shown that children go through a stage in which they know
      that the number words each refer to a distinct numerosity, yet do not know WHICH
      numerosity each number word picks out (Wynn, 1992). How do children attain this
      level of knowledge? We explore the possibility that particular properties of how
      number words are used within sentences inform children of the semantic class to
      which they belong. An analysis of transcripts of the spontaneous speech of three
      one- and two-year-old children and their parents (from the CHILDES database;
      MacWhinney & Snow, 1990) suggests that the relevant cues are available as input
      in parents' speech to children, and that children generally honour these
      properties of number words in their own speech. Implications of this proposal for
      word learning more generally are discussed.

PMID- 9519586
TI  - Using metaphors as modifiers: children's production of metaphoric compounds.
AB  - Although much research has investigated children's use of metaphoric language,
      methodological concerns raise questions about the conclusions, and it remains
      unclear whether preschoolers can produce metaphors. These studies employed a new
      methodology to test children's ability to produce metaphors incorporated into
      metaphoric compounds. In two studies, 59 children aged 2:8-4:3, 63 children aged
      4:4-6:1, and 34 adults participated in elicited production tasks. In Study 1,
      subjects in the COMPOUND condition corrected a puppet's incorrect compound labels
      for pictures that had metaphoric resemblances to other objects (e.g. 'leaf-bug'
      for a bug shaped like a stick). Subjects in the NONMETAPHORIC condition heard
      incorrect compounds describing pictures without obvious metaphoric resemblance
      (e.g. 'leaf-bug' for a round black beetle). Children in the REVERSAL condition
      heard compounds with nouns reversed (e.g. 'bug-leaf' for the stick-bug) to
      discover whether children distinguished between the literal and metaphoric
      labels. Study 2 provided an additional test of children's metaphoric-literal
      distinction. Results showed that children as young as 3:0 produced intentional,
      appropriate metaphors incorporated into compound nouns when the stimuli and
      puppet's labels primed recognition of metaphoric similarity and compound
      production. Moreover, children showed evidence of a distinction between literal
      and metaphoric labels. The data show that preschool children have an early
      ability to use metaphoric language but that significant developmental change
      occurs between the ages of 3:0 and 5:0 as well as beyond 5:0. Additionally,
      metaphoric language in preschoolers is not limited to single-word renamings.

PMID- 9519585
TI  - Caregiver speech and children's use of nouns versus verbs: a comparison of
      English, Italian, and Mandarin.
AB  - This paper examines naturalistic samples of adult-to-child speech to determine if
      variations in the input are consistent with reported variations in the
      proportions of nouns and verbs in children's early vocabularies. It contrasts two
      PRO-DROP languages, Italian and Mandarin, with English. Naturalistic speech
      samples from six 2:0 English-, six 1:11 Italian-, and ten 1:10 Mandarin-speaking
      children and their caregivers were examined. Adult-to-child speech was coded for
      the type frequency, token frequency, utterance position, and morphological
      variation of nouns and verbs as well as the types and placements of syntactic
      subjects and the pragmatic focus of adult questions. Children's spontaneous
      productions of nouns and verbs and their responses to adult questions were also
      examined. The results suggest a pattern consistent with the children's
      spontaneous production data. Namely, the speech of English-speaking caregivers
      emphasized nouns over verbs, whereas that of Mandarin-speaking caregivers
      emphasized verbs over nouns. The data from the Italian-speaking caregivers were
      more equivocal, though still noun-oriented, across these various input measures.

PMID- 9519587
TI  - Longitudinal measurement of growth in definitional skill.
AB  - This study examines individual growth rates in definitional skill over a period
      of three to six years, for 68 low-income children. Children were asked to define
      words once a year at school, from kindergarten (youngest administration at 5:3)
      through fourth grade (oldest administration at 10:10). A plateau was observed
      between age nine and ten both for percent formal definitions (characterized by
      presence of a superordinate) and for the quality of formal definitions. The
      plateau was lower than the theoretical ceiling for these measures. However, the
      children appear to have attained 'adult levels' of definitional skill: forty
      seven fourth-graders (aged 9:1 to 10:10) performed higher, on average, than their
      own mothers when giving definitions. These results support the notion that
      definitional skill is related to being part of an academic culture: low-income
      mothers, whose formal schooling is complete, generally do not give oral
      definitions to simple nouns as well as do their nine- to ten-year-old children.

PMID- 9519588
TI  - The role of prosody in the acquisition of grammatical morphemes: evidence from
      two Chinese languages.
AB  - This paper examines two issues concerning the acquisition of grammatical
      morphemes: (1) How is the acquisition of grammatical morphemes influenced by
      prosodic and phonological characteristics of the language being learned? and (2)
      What sorts of prosodic and phonological properties do grammatical morphemes have
      that might aid children in applying particular segmentation strategies? To
      address these issues, we compared the acquisition of grammatical morphemes in a
      pair of morphosyntactically similar but prosodically different languages, namely
      Taiwan Mandarin Chinese (TMC) and Taiwanese (TW). We analyse the patterns of
      realization and omission of a highly frequent subset of grammatical morphemes in
      six children's speech, recorded between the ages 1:6 and 2:3. The results from
      the between-language comparisons suggest that rhythmic characteristics of
      languages can affect segmentation by providing different kinds of prosodic
      handles for children to grasp at.

PMID- 9519589
TI  - Autonomous linguistic systems in the language of young children.
AB  - This paper considers cross-linguistic findings concerning the early development
      of formal, arbitrary, grammatical systems in normal hearing and deaf children and
      in children with congenital brain abnormalities. The paper reviews evidence
      showing an early acquisition of grammatical forms. Such learning is typically
      dissociated from the development of the relevant semantics. Form-function
      correspondences were not required for the development of morphological paradigms
      and for certain aspects of formal syntax. This finding held across all the
      populations studied. It is hypothesized that the autonomous nature of these
      formal paradigms accounts for their priority in learning cross-linguistically.

PMID- 9519590
TI  - Sources of support for learning words in conversation: evidence from mealtimes.
AB  - This study examines mealtimes of preschoolers' families to determine whether rare
      words are used in informative ways so that a child could learn their meanings. Is
      there an association between informative use of rare words and the child's later
      vocabulary? Each use of rare words in 160 transcripts was coded for whether it
      was informative or uninformative. Each informative exchange was coded for type of
      strategy used to provide support: physical or social context, prior knowledge,
      and semantic support. There were 1,631 exchanges around rare words. About two
      thirds of these exchanges were informative uses from which the child could learn
      the word's meaning. The most frequent strategy used was semantic support,
      accounting for two-thirds of strategies used. The frequency of use of rare words
      was positively correlated with age-five and age-seven PPVT scores.

PMID- 9519591
TI  - The effect of perceptual similarity and linguistic input on children's
      acquisition of object labels.
AB  - This study investigated whether and when children establish various semantic
      relations between old and new words. Fifty two-year-olds were taught labels for
      objects previously referred to by an overextended term. We found that children
      were more likely to learn a new label when (a) it referred to a new object that
      was perceptually dissimilar, rather than similar, to a known one, and (b) when
      linguistic information indicated it had an inclusion, rather than a mutually
      exclusive, relation to a known label. Children were more likely to interpret a
      new label as mutually exclusive to a known one when their referents were
      perceptually dissimilar. These findings are discussed in light of theories of
      lexical development, particularly with regard to conceptualizations of
      constraints on the acquisition of word meaning.

PMID- 9519592
TI  - Accommodation in mean f0 during mother-infant and father-infant vocal
      interactions: a longitudinal case study.
AB  - Reports that infants imitate the vocal pitch characteristics of adult caregivers
      (e.g. Lewis, 1936/1951) include Lieberman's (1967; Lieberman, Ryalls & Rabson,
      1982) claim that infants differentially adjust their vocal pitch or fundamental
      frequency (f0) towards that of their caregivers, resulting in higher mean pitch
      when interacting with mothers than when interacting with fathers. However, a
      recent cross-sectional study of infants at ages 0:8 to 0:9 and 1:0 failed to find
      evidence of differential pitch adjustment toward male and female caregivers
      (Siegel, Cooper, Morgan & Brennessie-Sarshad, 1990). A more sensitive test of
      Lieberman's claims would be to use a longitudinal design, with spontaneous
      recording sessions repeated over many months. The current study presents data
      from a longitudinal case study of an infant recorded at ages 0:3, 0:7, 0:10, 1:3
      and 1:5 interacting with each of her parents in spontaneous play sessions and in
      isolated play. The infant in our study did not demonstrate significant adjustment
      of her vocal pitch in the direction of either parent. However, we did find
      evidence for consistent adjustment by the parents, in accord with the literature
      on infant-directed speech and mother-infant dyadic interactions, which suggest
      that the parents adjusted their behavior to suit the infant more than vice versa.

PMID- 9519593
TI  - Word learning in a special population: do individuals with Williams syndrome obey
      lexical constraints?
AB  - Williams syndrome (WS), a rare neurodevelopmental disorder, is of special
      interest to developmental psycholinguists because of its uneven linguistico
      cognitive profile of abilities and deficits. One proficiency manifest in WS
      adolescents and adults is an unusually large vocabulary despite serious deficits
      in other domains. In this paper, rather than focus on vocabulary size, we explore
      the processes underlying vocabulary acquisition, i.e. how new words are learned.
      A WS group was compared to groups of normal MA-matched controls in the range 3-9
      years in four different experiments testing for constraints on word learning. We
      show that in construing the meaning of new words, normal children at all ages
      display fast mapping and abide by the constraints tested: mutual exclusivity,
      whole object and taxonomic. By contrast, while the WS group showed fast mapping
      and the mutual exclusivity constraint, they did not abide by the whole object or
      taxonomic constraints. This suggests that measuring only the size of WS
      vocabulary can distort conclusions about the normalcy of WS language. Our study
      shows that despite equivalent behaviour (i.e. vocabulary test age), the processes
      underlying how vocabulary is acquired in WS follow a somewhat different path from
      that of normal children and that the atypically developing brain is not
      necessarily a window on normal development.

PMID- 9519594
TI  - Overregularization in English plural and past tense inflectional morphology: a
      response to Marcus (1995).
AB  - In a recent note, Marcus (1995) suggests that the rate of overregularization of
      English irregular plural nouns is not substantively different from that of
      English irregular past tense verbs. This finding is claimed to be in conflict
      with the predictions of connectionist models (Plunkett & Marchman, 1991, 1993)
      which are said to depend solely on the dominance of regular over irregular forms
      in determining overregulation errors. However, these conclusions may be premature
      given that Marcus averaged overregulation rates across irregular nominal forms
      that varied in token frequency and across samples representing a broad range of
      children's ages. A connectionist view would predict an interplay between type
      frequency and other item level factors, e.g. token frequency, as well as
      differences in the developmental trajectories of the acquisition of nouns and
      verbs. In this response, we briefly review longitudinal parental report data (N =
      26) which indicate that children are significantly more likely to produce noun
      overregularizations than verb overregularizations across a prescribed age period
      (1:5 to 2:6). At the same time, these data also show that children are familiar
      with proportionately more irregular nouns than irregular verbs. These findings
      are consistent with the predictions of Plunkett & Marchman (1991, 1993) in that
      the larger regular class affects the frequency of noun errors but also that
      familiarity with individual irregular nouns tends to reduce the likelihood of
      overregularizations. In contrast to the conclusion of Marcus (1995), the
      connectionist approach to English inflectional morphology provides a plausible
      explanation of the phenomenon of overregularization in both the English plural
      and past tense systems.

PMID- 9519595
TI  - Parasitic infections among migrant farm families.
AB  - The prevalence of parasitic infestation is an indicator of the health, social,
      and economic conditions within a community. A retrospective study of 422 migrant
      farmworkers and their families found a prevalence of parasitic infestation of
      11.4%. The most significant predictors of infestation were mother's years of
      schooling (a low level of education was associated with infestation) and the
      prevalence of other parasitic infections within the family. No significant
      differences were found between infected and noninfected individuals in country of
      origin, time residing in the United States, father's years of schooling, sex, or
      age.

PMID- 9519596
TI  - Transmission of vancomycin-resistant enterococcus among family members: a case
      study.
AB  - Enterococci are persistent organisms naturally occurring in the digestive tract,
      able to persist on environmental surfaces for days or weeks, surviving heat and
      desiccation. They are the second most common bacterial cause of nosocomial
      infection. Recent strains of enterococci resistant to vancomycin pose a serious
      health hazard to hospitalized, institutionalized, and immunocompromised patients.
      This article presents a case study of community-acquired vancomycin-resistant
      enterococcus in an otherwise healthy child and suggests strategies for management
      and containment in the community.

PMID- 9519597
TI  - Evaluating critical thinking skills in a scenario-based community health course.
AB  - This study evaluated the influence of a scenario-based community health course on
      the ability of senior nursing students (N = 54) to address complex problems seen
      in the community health setting. In addition, we examined whether students'
      scores on the Watson-Glaser Critical Thinking Appraisal (WGCTA) questionnaire
      would differ depending on the size of the educational institution they attended
      before enrollment in a school of nursing and whether the types of electives
      (liberal arts or science) previously taken would influence the scores. Sign
      ficant improvements were seen on the Interpretation and Evaluation subscales and
      on the total critical thinking score from pretest to posttest for students who
      completed the course. Also students who completed nursing prerequisites in
      midsized, 4-year universities (10,000 to 30,000 students) had higher pretest mean
      scores on the majority of WGCTA subscales than did other students.

PMID- 9519598
TI  - Promoting health: perspectives from ethnic elderly women.
AB  - The purpose of this study was to investigate health-promoting measures used by
      ethnic elderly women. Within the context of this goal, two major research
      questions were asked: (a) What measures were used by the ethnic elderly women to
      promote their health? (b) What were the facilitators and barriers with respect to
      health promotion in this sample? A convenient and purposive sample consisted of
      30 elderly women from three ethnic backgrounds--African American, Chinese
      American, and European American--who reside in an urban area of the northeastern
      part of the United States. Data were collected through in-depth interviews and
      survey questionnaires. Content and statistical analyses were employed.
      Participants identified measures, facilitators, and barriers in relation to
      promoting their health. These findings provide insight for community health
      nursing practice.

PMID- 9519599
TI  - Increasing cultural competence with the Latino community.
AB  - There is growing recognition among health professionals that being familiar with
      the culture of a particular group and developing effective partnerships to
      involve group members in the production of their own health are essential
      strategies to promote health. Moreover, it is increasingly recognized that
      providing health care services that are culturally sensitive can result in
      improved health status for clients. This article describes selected Latino
      cultural customs that can enhance a nurse's ability to work sensitively and
      effectively with this ethnic group. Creative strategies to increase the cultural
      competence of nurses involved in primary care settings are also presented.

PMID- 9519600
TI  - Ingrown nails: a comparison of the nail matrix phenolization method with the
      elevation of the nail bed-periosteal flap procedure.
AB  - Seventy-five procedures were performed on 62 patients with ingrown nails from
      1992 to 1996. Those consisted of 51 nail matrix phenolization methods (NMP) and
      24 elevation of the nail bed-periosteal flap procedures (ENF). Ingrown nails were
      classified into type A (normal nail plate) and type B (incurved nail plate). The
      duration and intensity of postoperative pain were assessed, and the recurrence
      rate was monitered. The recurrence rate was 3.9% in the NMP group and 4.1% in the
      ENF group. Concerning the recurrence rate, there was no statistical significance
      between ENF and NMP in both types. Postoperative pain intensity was less in the
      NMP group than in the ENF group in both types (P < 0.01). The same tendency was
      seen in postoperative pain duration. However, the NMP group had longer duration
      of wound healing compared with the ENF group in type A (P < 0.01). We conclude
      that NMP is a recommendable treatment for most ingrown nails.

PMID- 9519601
TI  - Elastic fibers in dermis of juvenile elastoma.
AB  - To explore the ultrastructure of elastic fibers in juvenile elastoma, three
      patients (two without osteopoikilosis and one under examination of bones and
      joints) were studied by routine electron microscopy. In addition to normal
      elastic fibers, all the patients also exhibited alterations in elastic fibers.
      The altered ultrastructures showed lucent, homogenous matrix without peripheral
      microfibrils. The homogenous matrix were seen in various extensions from the
      small protrusions of the normal elastic fibers to the complete replacement of the
      entire fibers. Collagen fibrils occasionally showed twisted figures. Normal
      shapes of dermal glycosaminoglycans were increased in number. It seems likely
      that the lucent, homogenous matrix without peripheral microfibrils are the
      characteristic changes of elastic fibers in juvenile elastoma. The alteration
      could be nevoid in nature.

PMID- 9519602
TI  - Microscopically controlled surgical excision combined with ultrapulse CO2
      vaporization in the management of a patient with the nevoid basal cell carcinoma
      syndrome.
AB  - Nevoid basal cell carcinoma syndrome is an autosomal dominant condition
      characterized by multiple basal cell carcinomas, skeletal abnormalities and
      sometimes mental retardation. The large number of tumors, which are often
      disfiguring, presents extreme difficulties in the treatment of these patients.
      Microscopically controlled excision, compared to other modalities (radiation
      therapy, photodynamic therapy, intralesional interferon alpha-2b) offers the
      highest cure rate. However, because of the large size and involvement of wide
      areas of the skin, this approach is sometimes impractical. The ultrapulse CO2
      laser with high energy and short pulses achieves char-free ablation of the
      tumors, bloodless surgical field, minimal nonspecific thermal damage, rapid
      healing and diminished postoperative pain. Also, a number of lesions can be
      removed in a single session. We present a 48-year-old man with a 6.5 x 4.5 cm
      large basal cell carcinoma involving the anterior abdomen and navel area. The
      central thick portion of the tumor was resected by microscopically controlled
      excision with 3 stages, and wide thinner peripheral crescentic plaque vaporized
      with ultrapulse CO2 laser. The laser settings were 300 mJ energy/pulse and 100 W
      average power, which corresponds to the fluence of 7.5 J/cm2. Computerized
      pattern generator (ultrascan handpiece) was adjusted to patterns of 3 (circle)
      and 1 (square) with sizes varying from 5 to 7, and density of 9 (60%
      overlapping). The tumor was vaporized with 6 passes, all the way to deep
      reticular dermis. A fifteen month-follow up disclosed no recurrent disease.
      Subsequent biopsies revealed only a scar with postinflammatory hyperpigmentation.
      Our experience indicates that combined treatment with microscopically controlled
      excision and ultrapulse CO2 laser ablation is a suitable modality for the large
      tumor plaques involving concave and convex areas of the skin respectively.
      Microscopically controlled excision of thicker, concave portions of basal cell
      carcinoma plaques, where CO2 laser surgery is less feasible, presents an
      effective addition that renders this combined modality a successful method for
      the treatment of nevoid basal cell carcinoma syndrome.

PMID- 9519603
TI  - An erythema multiforme-like eruption caused by exposure to 1
      chloromethylnaphthalene.
AB  - A young male patient developed an erythema multiforme-like eruption following an
      accidental exposure to 1-chloromethylnaphthalene (1-CMN). In addition to the skin
      lesion, he suffered from liver involvement and tear insufficiency. Positive
      results of a patch test with 1-CMN and an in vitro lymphocyte transformation test
      suggested that direct exposure of the skin to chemical compounds was the probable
      cause of his symptoms.

PMID- 9519605
TI  - Acral lentiginous nevus.
AB  - In non-Caucasians, malignant melanoma most frequently affects the sole of the
      foot. To improve the prognosis in such patients, accurate diagnosis of early
      lesions is extremely important, and, to avoid potentially mutilating surgery, it
      is equally important to identify benign acral nevus. Clemente and colleagues
      recently proposed a new clinicopathological entity, designated acral lentiginous
      nevus (ALN) of the plantar skin. The clinical and histopathological
      characteristics of these nevi enable clinicians to distinguish them from ordinary
      nevi and melanoma. We report four additional cases of ALN, which can be
      classified as belonging to the "pseudomelanoma" group.

PMID- 9519604
TI  - Epidermolysis bullosa acquisita localized to the face.
AB  - A 39-year-old woman had a three-year history of recurrent bullous eruption
      localized to her left cheek. The diagnosis of epidermolysis bullosa acquisita was
      confirmed by means of direct immunofluorescence and direct immunoelectron
      microscopic studies performed on the perilesional salt-split skin. Topical
      corticosteroid treatment reduced pruritus and bullae formation. This case of
      localized epidermolysis bullosa acquisita on the face is reminiscent of Brunsting
      Perry cicatricial pemphigoid. We also review the previously reported cases of
      localized epidermolysis bullosa acquisita.

PMID- 9519606
TI  - Drug eruption (erythema multiforme type) due to a digestive enzyme drug.
AB  - An 84-year-old Japanese male had pruritic indurated erythema on his upper limb
      and left lower abdomen, which had developed abruptly two months before visiting
      our hospital. Hematological examination showed eosinophilia, 550/mm3.
      Histopathological findings were suggestive of erythema multiforme in response to
      a drug. By means of patch tests and a p.o. challenge test, Aczym, a digestive
      enzyme drug, was shown to be the cause of his condition. Further study revealed
      that the specific ingredients involved were pancreatin and Taka-diastase. An
      eruption resulting from ingestion of a digestive enzyme drug has not previously
      been reported.

PMID- 9519607
TI  - An autopsy case of dermatomyositis with rapidly progressive diffuse alveolar
      damage.
AB  - A 47-year-old woman visited a clinic with dyspnea which had continued for two
      months and was followed by general fatigue and fever. Antibiotics were not
      effective. Edematous erythema occurred on her face, elbows, knees and feet, and
      she entered our hospital. A skin biopsy revealed interface dermatitis with severe
      edema and mucinosis in dermis. Diffuse bilateral infiltration was observed in the
      chest X-ray, and laboratory findings showed increased LDH, GPT, GOT and CPK. No
      antinuclear factor was detected. Her respiratory condition rapidly worsened, and
      she died eight days after hospitalization in spite of corticosteroid pulse
      therapy. The autopsy revealed that the main cause of death was diffuse alveolar
      damage (DAD). Interstitial pneumonia related to dermatomyositis is not
      histologically uniform; the response to the therapy depends on its histological
      type. The patients with dermatomyositis who have poor prognosis are clinically
      characterized by acute onset with general symptoms and less pronounced muscle
      weakness; they generally show DAD in their lungs. We need to establish a simple
      method for distinguishing histological types of interstitial pneumonia and
      adequate therapy for each one.

PMID- 9519608
TI  - Cutaneous disseminated actinomycosis in a patient with acute lymphocytic
      leukemia.
AB  - Actinomycosis is an uncommon infectious disease caused predominantly by
      Actinomyces israelii. The cutaneous disseminated form is usually caused by
      hematogenous dissemination from a primary extra-cutaneous lesion. We report here
      cutaneous disseminated actinomycosis without any detectable extra-cutaneous
      lesions in a 42-year-old Japanese woman with acute lymphocytic leukemia. Multiple
      soft nodules developed on her upper and lower extremities. Histopathological
      examination revealed "sulfur granules", which are a specific finding for
      actinomycosis. Cultures from biopsy specimens were not successful. There were no
      cervicofacial, thoracic, nor abdominal lesions. These findings suggest that
      cutaneous disseminated actinomycosis in our patient developed primarily in the
      skin. Although the patient was immunocompromised, antibiotic treatment with
      minocycline was effective.

PMID- 9519609
TI  - Malignant melanoma in situ arising in the nail unit of a child.
AB  - A very rare case of malignant melanoma in situ of the nail unit of a child is
      presented. Clinically, a pigmented streak was present on the finger nail of a 3
      year-old girl, and the lesion increased in size and in darkness of the color
      associated with periungual pigmentation in the following two years.
      Histopathologically, sections showed proliferation of atypical melanocytes,
      arranged mostly in single units but some in nests, in and above the basal layer
      of the epithelium and admixed with long dendrites and a few mitotic figures.
      Pigmented lesions of nail units of children often show fading or loss of
      pigmentation clinically; however, a biopsy should be done when they show
      augmentative changes which clinically suggest malignancy, because subungual
      malignant melanoma can exist even in children, and proper biopsy can detect it in
      its early stages.

PMID- 9519610
TI  - Merkel cell carcinoma: report of three cases.
AB  - Three cases of Merkel cell carcinoma are reported: Case 1 on the upper eyelid
      with regional lymph node metastasis, Case 2 with spontaneous regression after
      repeated biopsies, and Case 3 presumably developing on the lesion of pre-existing
      Bowen's disease. In Case 2, the biopsy specimen was characterized by numerous
      apoptotic cells in the periphery of the tumor nests surrounded by lymphocytic
      infiltration. In Case 3, the tumor developed after injury to the pre-existing
      lesion of Bowen's disease.

PMID- 9519611
TI  - Disseminated and recurrent infundibular folliculitis (D.R.I.F.): report of a case
      successfully treated with isotretinoin.
AB  - Disseminated and recurrent infundibular folliculitis, henceforth referred to as
      D.R.I.F., is a very rare, puritic, follicular, benign disease of unknown etiology
      seen mostly in black males. It is often self-limited and usually unresponsive to
      local or systemic treatment. However, vitamin A, either alone or combined with
      vitamin E, is occasionally effective. We report a case of a patient with D.R.I.F.
      treated successfully with isotretinoin.

PMID- 9519613
TI  - Is the heredity of reticulate acro pigmentation of Kitamura always autosomal
      dominant?
AB  - Reticulate acropigmentation of Kitamura (RAK) in three patients and their
      families is described. In one family, 2 women and 2 men were affected out of 9
      individuals. In the other family, 6 women had lesions of reticulate
      acropigmentation out of total of 27 over three generations. In the third family,
      one man was affected. All of the cases had palmar pits; onset of lesions was
      after puberty in all the cases. The apparently different hereditary patterns in
      these three families are striking, and autosomal dominant inheritance appears
      unlikely in every case.

PMID- 9519612
TI  - Familial reactive perforating collagenosis: a case report.
AB  - Reactive perforating collagenosis is characterised by trans-epidermal elimination
      of collagen and is hypothesized to be both autosomally dominant and recessive. We
      report a family in which two brothers and a sister had lesions of reactive
      perforating collagenosis.

PMID- 9519614
TI  - A case of subungual osteochondroma.
AB  - Subungual osteochondroma is a rare form of benign bone tumor characterized by
      distinctive histopathological and radiological findings. The major clinical
      manifestation is a firm mass with tenderness. It must be differentiated from
      other similar diseases such as subungual exostosis, glomus tumor, and enchondroma
      to determine the proper surgical procedure. A 13-year-old boy had a history of a
      growing tender mass on the right third toe which recurred after simple excision.
      He was treated by careful dissection and total excision under local anesthesia.
      Histologic findings included a trabecular bone formation covered with hyaline
      cartilage cap and were compatible with osteochondroma.

PMID- 9519615
TI  - Relapse (reactivation) in borderline tuberculoid (BT) leprosy.

PMID- 9519617
TI  - Lessons for the health care industry from America's experience with public
      utilities.
AB  - In the United States, the traditional public utilities, power and
      telecommunications, along with health care, are being deregulated and becoming
      increasingly competitive, especially on price. Regulation of the public utilities
      has occurred for the past century not simply because they have been monopolies,
      but, more importantly, because they are "industries affected with the public
      interest," that is industries which: 1. provide an essential service, 2. benefit
      from public prequisites, and 3. would cause great public harm if mismanaged.
      Consequently, the presence of competition in these industries does not negate the
      need for regulation. Regulation of these industries is best understood as being
      along the three sides of a "triangle of public interests"--quality, public
      accountability, and universal service. Examples are provided of these types of
      regulation in power and telecommunications, even in current "deregulatory"
      legislation. Health care reform activists in the United States have lately paid
      attention mostly to the first two legs of the triangle; they are encouraged to
      focus creatively on the third leg--universal health care.

PMID- 9519616
TI  - Psoriasis occurring in amelanotic lesions.

PMID- 9519618
TI  - HIV testing of pregnant women: a policy analysis.
AB  - The promising findings of ACTG 076, which identified a hopeful strategy for
      substantially reducing HIV transmission from mother to fetus, has stimulated a
      debate on counseling and testing protocols for pregnant women. This article
      presents an analysis of five state policy alternatives that address HIV
      counseling and testing. The policy analysis utilizes vertical and horizontal
      equity, user preference including avoidance of stigma and the right to privacy,
      effectiveness, and feasibility as evaluative criteria for examination of the
      policies. Interviews with state health department personnel enhance the policy
      analysis. While universal HIV counseling and voluntary testing for pregnant women
      emerges as the most acceptable policy, public health professionals must assume a
      vital role in facilitating the adoption of ethical and just state policies in an
      atmosphere sometimes hostile to women at risk for HIV.

PMID- 9519619
TI  - Labor positions on worksite tobacco control policies: a review of arbitration
      cases.
AB  - Although worksite smoking restrictions have become increasingly common in recent
      years, organized labor has generally not been involved in the adoption of these
      policies; some evidence suggests that unions often oppose the adoption of
      worksite smoking policies. To contribute to an understanding of labor's role in
      tobacco control policies, this paper reports the results of a review of 85
      arbitration cases and 5 cases of unfair labor practices charges published between
      1986 and 1994. In most of the cases reviewed, management unilaterally imposed a
      new smoking policy, which the union then grieved. Union opposition to the policy
      generally focused on the process by which the policy was adopted, rather than the
      content of the policy; the concern was that management had breached its duty to
      bargain with the union regarding the adoption of the policy. These results
      underline the importance of joint labor-management actions on worksite tobacco
      control policies.

PMID- 9519620
TI  - Finding common ground: how public health can work with organized labor to protect
      workers from environmental tobacco smoke. National Association for Public Health
      Policy.
AB  - Tobacco is not and does not have to be a high priority for all segments of
      organized labor, but public health advocates should continue to promote the issue
      and find segments which are open to collaborative efforts to protect workers'
      health. Even in those unions representing workers for whom smoking and ETS pose a
      lower health risk relative to other workplace toxins, smoking policy remains a
      strategic issue for at least two reasons. First, supporting efforts to control
      ETS exposure sure is an issue of service to non-smoking union members, and like
      wise, bargaining for smoking cessation programs is a service to members who
      smoke. Second, it is in the union's interest to engage with management through
      collective bargaining to develop smoking policies, rather than to allow
      management to unilaterally propose and/or implement policies. To remain a strong
      voice in the worksite, labor needs to defend its unions and members from
      misdirected and overzealous actions. Within the context of the diversity of
      opinions from within labor and public health, this policy statement aims to
      identify our common ground and recommend ways to collaborate in protecting worker
      health. Specifically, we recommend that the public health community take the
      following actions: I) assist unions with smoking cessation services that meet the
      needs of labor, 2) support labor's efforts to negotiate smoking policies within
      the context of collective bargaining, 3) include labor in tobacco control
      coalitions, 4) advocate for regulatory initiatives that include ETS as part of an
      overall indoor air quality strategy, 5) focus attention on preventing smoking
      among children of union members, and 6) develop strategies with labor to benefit
      from savings that employers achieve under smoking restrictions or bans. Smoking
      and exposure to second-hand smoke represent a threat to the health of workers.
      Given that the public health and labor movements have a mutual interest in
      protecting worker health, it makes sense for these two groups to join together on
      tobacco control policy-making in the worksite.

PMID- 9519621
TI  - Women and smoking. National Association for Public Health Policy.

PMID- 9519622
TI  - Re "A critique of an evaluation of the impact of hospital bed closures in
      Winnipeg, Canada: lessons to be learned from evaluation research methods" by
      Evelyn Vingilis and Jacquelyn Burkell.

PMID- 9519623
TI  - Gender identity disorder.

PMID- 9519624
TI  - Risperidone-induced hepatotoxicity?

PMID- 9519626
TI  - Medication-induced hypomania in Asperger's disorder.

PMID- 9519625
TI  - Stimulants and neuroleptic withdrawal dyskinesia.

PMID- 9519627
TI  - Outpatient pharmacotherapy in a community mental health center.

PMID- 9519628
TI  - Child psychiatry in Estonia.

PMID- 9519629
TI  - Adolescent substance abuse: a review of the past 10 years.
AB  - OBJECTIVE: To review and synthesize the recent scientific literature on
      adolescent substance abuse, covering natural history, epidemiology, etiology,
      comorbidity, assessment, treatment, and prevention, and to highlight areas for
      future research. METHOD: Studies of adolescent substance abuse were reviewed with
      the focus on substance abuse and dependence rather than substance use. RESULTS:
      There has been a sharp recent resurgence in adolescent drug use. Biological
      factors, including genetic and temperament characteristics, as well as family
      environment factors, are emerging as important etiological variables. Comorbidity
      with other psychiatric disorders, particularly with conduct disorder, is frequent
      and complicates treatment. New assessment instruments are available for clinical
      and research use. Among treatment modalities, family-based interventions have
      received the most study. CONCLUSIONS: The past decade has seen growth in the
      volume and sophistication of research on adolescent substance abuse and in the
      conceptualization of this problem. Further research is needed, particularly on
      the significance of comorbid conditions and on individualized and effective
      treatment approaches.

PMID- 9519630
TI  - Psychopathology and health care use among preschool children: a retrospective
      analysis.
AB  - OBJECTIVE: To examine the relationship between psychopathology and health care
      utilization beginning in the preschool (ages 2 to 5) years. METHOD: Five hundred
      ten preschool children were enrolled through 68 primary care physicians. The test
      battery used for diagnoses included the Child Behavior Checklist, a developmental
      evaluation, the Rochester Adaptive Behavior Inventory, and a videotaped play
      session. Consensus DSM-III-R diagnoses were assigned using best-estimate
      procedures. Frequency of primary care visits was established through 1-year
      retrospective record review; mothers estimated total visits and emergency
      department (ED) use. RESULTS: Logistic regression models showed that a DSM-III-R
      diagnosis was related to increased ED use but not primary care or total visits.
      Greater functional impairment was associated with fewer primary care visits and
      more ED visits. Total, internalizing, and externalizing behavior problem scores
      were associated with increased primary care and total visits; ED visits were
      associated with increased total and internalizing problems. Child's health status
      consistently correlated with utilization. CONCLUSION: There is a consistent
      relationship between health care use and child psychopathology beginning in the
      preschool years.

PMID- 9519631
TI  - A dimensional classification of autism spectrum disorder by social communication
      domains.
AB  - OBJECTIVE: To investigate whether "social communication" could be used to assess
      severity of symptoms in autism spectrum disorder. Social communication refers to
      the communication of cognitive and emotional information through facial
      expression, gesture, and prosody and through implicit understanding of pragmatics
      and of theory of mind. METHOD: Subjects were evaluated by raters using the Autism
      Diagnostic interview-Revised and either the Autism Diagnostic Observation
      Schedule or the Pre-Linguistic Autism Diagnostic Observation Schedule. Two
      investigators independently diagnosed autism, Asperger's disorder, or pervasive
      developmental disorder-not otherwise specified in 63 subjects. Items from the
      Autism Diagnostic Interview-Revised that were judged to represent social
      communication behaviors were factor-analyzed. RESULTS: Three factors were
      identified: affective reciprocity, joint attention, and theory of mind. Comparing
      this new classification approach to DSM-IV led to suggestions for possible
      changes in the latter: (1) Vocabulary and grammar deficiencies in autistic
      persons should be coded under developmental language disorder, (2) The diagnosis
      of Asperger's disorder may not be needed. (3) Requiring that all persons with
      autism spectrum disorder have a symptom from the "restrictive, repetitive, and
      stereotypic" list may need to be reconsidered. CONCLUSIONS: The DSM-IV category
      of pervasive developmental disorder may be ideal for diagnosing "classic" autism,
      but it may be inadequate for diagnosing less severe forms of the disorder.

PMID- 9519632
TI  - Reliability and accuracy of differentiating pervasive developmental disorder
      subtypes.
AB  - OBJECTIVE: To evaluate the ability of the DSM-IV criteria for the pervasive
      developmental disorders (PDD) to reliably and accurately differentiate PDD
      subtypes. METHOD: The sample consisted of 143 children with various types of
      developmental disabilities. A diagnosis of PDD and PDD subtype was made by one
      clinician using information obtained from the Autism Diagnostic Interview-Revised
      and the Autism Diagnostic Observation Schedule. The raw data from the Autism
      Diagnostic Interview-Revised, clinical notes (excluding diagnostic opinion),
      Autism Diagnostic Observation Schedule, IQ, and other available data were
      independently assessed by three experienced raters, each of whom then made a
      separate, blind diagnosis. If there was any disagreement, a consensus best
      estimate (CBE) diagnosis was made after discussion. To assess reliability, the
      agreement between the three raters was calculated using k. Accuracy was assessed
      by calculating the agreement between the clinician's diagnosis and the CBE and by
      calculating the error rates associated with the three raters using latent class
      analysis. RESULTS: The current DSM-IV criteria show good to excellent reliability
      for the diagnosis of PDD, Asperger's disorder (AsD), and autism, but they show
      poor reliability for the diagnosis of atypical autism. The clinician (compared to
      the CBE) had little difficulty differentiating PDD from non-PDD children and
      autism from AsD but had more difficulty identifying children with atypical
      autism. The latent class analysis also showed that the average error rates of the
      three raters for a differentiation of atypical autism from autism were
      unacceptably high. CONCLUSIONS: Although the psychometric properties of the
      current DSM-IV criteria for autism and AsD appear quite acceptable, there is
      likely to be a high rate of misclassification of children given a diagnosis of
      atypical autism.

PMID- 9519633
TI  - Transition from adolescence to early adulthood: adaptation and psychiatric status
      of women with 47,XXX.
AB  - OBJECTIVE: To investigate the adolescent and early adult adaptation of a group of
      47,XXX women as compared with their siblings, addressing developmental
      differences in adaptation and psychiatric status. METHOD: Subjects included
      eleven 47,XXX women and nine female sibling controls. Interviews during
      adolescence and during early adulthood were semistructured and included a
      psychiatric evaluation. Four areas of inquiry were (1) relationships with other
      family members, (2) sense of self-esteem, (3) sexual identity and preference, and
      (4) responses to life stressors. A DSM-IV psychiatric diagnosis was assigned
      where appropriate. The Schedule for Affective Disorders and Schizophrenia
      Lifetime version was also administered, and assessments of overall functioning
      and adaptation were completed. RESULTS: The 47,XXX women during adolescence and
      young adulthood were less well adapted; had more stress; had more work, leisure,
      and relationship problems; had a lower IQ; and showed more psychopathology when
      contrasted with the comparison group. However, most of the 47,XXX women were self
      sufficient and functioning reasonably well, albeit less well than their siblings.
      CONCLUSIONS: This longitudinal study has clarified that previously reported
      outcomes of severe psychopathology and antisocial behavior in individuals with
      sex chromosome anomalies are rare and variability in the behavioral phenotype is
      much larger than originally appreciated.

PMID- 9519634
TI  - Brief report: association of sex chromosome anomalies with childhood-onset
      psychotic disorders.
AB  - OBJECTIVE: An apparent excess of sex chromosome aneuploidies (XXY, XXX, and
      possibly XYY) has been reported in patients with adult-onset schizophrenia and
      with unspecified psychoses. This study describes the results of cytogenetic
      screening carried out for pediatric patients meeting DMS-III-R criteria for
      childhood-onset schizophrenia (COS) and a subgroup of patients with childhood
      onset psychotic disorder not otherwise specified, provisionally labeled by the
      authors as multidimensionally impaired (MDI). METHOD: From August 1990 to July
      1997, karyotypes were determined for 66 neuroleptic-nonresponsive pediatric
      patients (28 MDI, 38 COS), referred to the National Institute of Mental Health
      for an inpatient treatment trial of clozapine. RESULTS: Four (6.1%) of 66
      patients (3 MDI, 1 COS) were found to have sex chromosome anomalies (mosaic
      47,XXY; 47,XXY; 47,XYY; mosaic 45,XO, respectively), which is higher than the
      expected rate of 1 per 426 children or 2.34 per 1,000 in the general population
      (4/66 versus 1/426, chi 2 = 19.2, df = 1, p = .00001). All cases had been
      previously undiagnosed. CONCLUSIONS: These findings lend support to a hypothesis
      that a loss of balance of gene products on the sex chromosomes may predispose
      affected individuals to susceptibility to additional genetic and environmental
      insults that result in childhood-onset psychotic disorders. Karyotyping of
      children with psychotic disorders should be routine.

PMID- 9519635
TI  - The Neuropsychiatric Rating Schedule: reliability and validity.
AB  - OBJECTIVE: To evaluate reliability and validity for the Neuropsychiatric Rating
      Schedule (NPRS) interview designed to permit diagnosis of organic personality
      syndrome (OPS) or personality change due to a general medical condition (PC).
      METHOD: Subjects from prospective (n = 50) and retrospective (n = 72) studies of
      traumatic brain injury were aged 6 through 18 years. Parents and children were
      informants for the NPRS. Convergent and discriminant validity of subtypes of
      OPS/PC were assessed against standard scales completed by parents and teachers.
      Interrater reliability data (n = 20), test-retest reliability data (n = 42), as
      well as sensitivity-to-change data (n = 37) were collected. RESULTS: All subtypes
      of OPS/PC were diagnosed, but apathy and paranoia subtypes were rare. Rating
      scale data supported convergent validity of OPS/PC subtypes generated with the
      NPRS. Affective instability, rage/aggression, and inappropriate social judgment
      were moderately to highly correlated, but apathy and paranoia could be
      discriminated from each of these subtypes. Interrater agreement for NPRS items
      was fair to excellent for all but one item (paranoia). Test-retest reliability
      was fair to good, and sensitivity to change was demonstrated. CONCLUSION: The
      NPRS generated reliable and valid diagnoses of the common subtypes of OPS/PC.

PMID- 9519636
TI  - Diagnostic continuity between child and adolescent ADHD: findings from a
      longitudinal clinical sample.
AB  - OBJECTIVE: To determine whether there are differences in the clinical expression
      and correlates of attention-deficit hyperactivity disorder (ADHD) between
      children and adolescents. METHOD: Subjects were 6- to 17-year old Caucasian, non
      Hispanic boys with and without ADHD. DSM-III-R structured diagnostic interviews,
      psychometric measures, and blind raters assessed psychiatric diagnoses,
      intellectual performance, social disability, school failure, and family
      functioning. RESULTS: Children and adolescents with ADHD had an almost identical
      pattern of correlates in multiple domains of assessment including psychosocial
      adversity and comorbidity with conduct, mood, and anxiety disorders. Although the
      rate of substance abuse differed in comparison between child and adolescent
      subjects, this was independent of ADHD status. CONCLUSIONS: These findings
      document the diagnostic continuity of ADHD between childhood and adolescence and
      support the inclusion of adolescent samples in ADHD research protocols.

PMID- 9519638
TI  - Longitudinal study of co-occurring psychiatric disorders and substance use.
AB  - OBJECTIVE: To examine temporal priority in the relationship between psychiatric
      disorders and drug use. METHOD: Psychiatric assessments and drug use were
      completed at three different points in time, spanning 9 years. Structured
      interviews were administered to a cohort of youths and their mothers. Subjects
      were selected on the basis of their residence in either of two counties in
      upstate New York. The sample was predominantly white male and female youths, aged
      1 through 10 years upon initial collection of data. Psychiatric diagnoses were
      assessed by a supplemented version of the Diagnostic Interview Schedule for
      Children Version 1, using computer algorithms designed to match DSM-III-R
      criteria to combine information from mothers and youths. Substance use
      information was obtained in the interviews. RESULTS: A significant relationship
      was found to exist between earlier adolescent drug use and later depressive and
      disruptive disorders in young adulthood, controlling for earlier psychiatric
      disorders. Earlier psychiatric disorders did not predict changes in young adult
      drug use. CONCLUSIONS: Implications for policy, prevention, and treatment include
      (1) more medical attention needs to be given to the use of legal and illegal
      drugs; and (2) a decrease in drug use may result in a decrease in the incidence
      of later psychiatric disorders.

PMID- 9519639
TI  - Clinical approach to treatment of ADHD in adolescents with substance use
      disorders and conduct disorder.

PMID- 9519640
TI  - Development of the cerebral cortex: III. The reeler mutation.

PMID- 9519637
TI  - Equivalent effects of stimulant treatment for attention-deficit hyperactivity
      disorder during childhood and adolescence.
AB  - OBJECTIVE: To compare the therapeutic effect size of methylphenidate on attention
      deficit hyperactivity disorder (ADHD) during childhood versus adolescence.
      METHOD: A retrospective follow-up study of 16 individuals with diagnosed ADHD who
      completed double-blind, placebo-controlled, crossover studies of methylphenidate
      0.3 mg/kg during two separate summer treatment programs. The programs were
      completed when the subjects were children (aged 8 to 11 years) and adolescents
      (aged 12 to 14.5 years). Dependent variables include objective measures of
      academic performance and social behavior and ratings completed by counselors and
      teachers. RESULTS: Effect sizes ranged from very large to small, with most
      effects in the moderate to large range. Across the 12 dependent variables, t
      tests found that only 3 showed statistically significant changes in effect size
      from childhood to adolescence. Putative changes in effect sizes can be dismissed
      for methodological reasons. CONCLUSION: Stimulant medication is equally effective
      with children and adolescents with ADHD if they are engaged in similar
      activities. Treatment providers should rigorously examine environmental causes to
      problems before prescribing higher doses of stimulants to adolescents with ADHD
      who exhibit a worsening in functioning.

PMID- 9519641
TI  - Poison centers and drug identification.

PMID- 9519642
TI  - Drug therapy for obesity: clarifications.

PMID- 9519643
TI  - Assessing problems with medication regimen adherence.

PMID- 9519644
TI  - Hepatitis C: infection and current treatment strategies.

PMID- 9519645
TI  - Expanding pharmacy's horizons: VA's pharmacotherapy innovations.

PMID- 9519646
TI  - The global problem of antimicrobial resistance.
AB  - Along with other multidrug-resistant pathogens previously identified,
      Streptococcus pneumoniae is becoming a serious concern in hospital and ambulatory
      care settings. The AIDS pandemic has increased the threat of resistance in
      Mycobacterium tuberculosis. Antimicrobial drug resistance involves three
      molecular mechanisms drug inactivation, altered cell permeability, and alteration
      of target sites. Surveillance and multidisciplinary approaches will be key to
      containing the threat of global antimicrobial resistance.

PMID- 9519647
TI  - Evaluation of drug information in an Internet newsgroup.
AB  - OBJECTIVE: To determine the accuracy and potential harmfulness of the drug
      information in a newsgroup on the Internet, sci.med.pharmacy. DESIGN: In this
      cross-sectional study, two independent reviewers analyzed the nonsubjective drug
      information in this newsgroup. Drug information was classified as correct,
      incorrect or could not verify. Information was determined to have no harm, minor
      harm, moderate harm, or severe harm. RESULTS: About one-half of the drug
      information was found to be correct in this newsgroup. Although 68% of the drug
      information was found to result in no harm, 19.4% was classified as harmful.
      CONCLUSIONS: If drug information on the Internet contains inaccuracies, its ready
      accessibility may pose a public health problem. With the number of Internet users
      growing, health professionals need to be aware of the potential for dissemination
      of misinformation, and need to become familiar with the Internet and the various
      health information resources available to the public.

PMID- 9519648
TI  - Problems with folic acid dissolution: public health perspective.

PMID- 9519649
TI  - Failure of prescription prenatal vitamin products to meet USP standards for folic
      acid dissolution.
AB  - OBJECTIVE: To determine whether prescription prenatal vitamins meet United States
      Pharmacopeial Convention (USP) standards for folic acid dissolution. METHODS:
      Dissolution was measured using USP Apparatus II and test conditions specified in
      the 23rd revision of the United States Pharmacopeia (USP 23). Folic acid was
      assayed by a chromatographic method modified from that specified in the official
      monographs, for oil- and water-soluble vitamins with minerals tablets, in USP 23.
      RESULTS: Only three out of nine multivitamin products met USP specifications for
      folic acid release. Most missed by a wide margin; folic acid dissolution from two
      products was less than 25%. CONCLUSIONS: Because a wide variety of brand-name and
      generic prescription prenatal multivitamin products were tested, these results
      are likely to be representative of the multivitamin products on the market. Given
      the significance of folic acid to public health, the authors believe that this
      subject should be studied further and that prompt action should be taken to
      ensure that folic-acid-containing products are of the highest quality possible.

PMID- 9519650
TI  - Impact of OBRA '90 on pharmacists' patient counseling practices.
AB  - OBJECTIVE: To assess the impact of OBRA '90 regulations on the counseling
      practices of community pharmacists in Nebraska. METHODS: A telephone survey was
      conducted of 80 randomly selected community pharmacies throughout Nebraska. A
      modified written survey was mailed to the 34 telephone nonrespondents and to
      another 86 randomly selected community pharmacists. A composite response rate
      (combining both survey methods) of 67.5% (112 of 166) was obtained, and responses
      were sorted into an independent community pharmacy group (n = 80) and a chain
      pharmacy group (n = 32). RESULTS: Only 44.6% of respondents reported that time
      devoted to patient counseling had increased as a result of OBRA '90. Chain
      pharmacists generally devoted more time to counseling after OBRA '90 became
      effective than did independent community pharmacists. CONCLUSION: While more than
      three out of four pharmacists felt adequately prepared for mandated patient
      counseling, fewer than half reported that time devoted to counseling had
      increased. Although the profession is moving toward the standard of
      pharmaceutical care, many pharmacists are not yet counseling as the law requires.

PMID- 9519651
TI  - Drug use during lactation.
AB  - Breast-feeding is an essential physiologic process that provides ideal nutrition
      to the infant as well as protection against disease. All drugs are excreted into
      breast milk and are bioavailable to the infant. However, most medications do not
      pose significant risk to the nursing infant, and breast-feeding should be
      continued despite medication use in most cases. These decisions should be made
      using a stepwise approach Pharmacists should be aware of which drugs are
      contraindicated and which drugs should be used cautiously, in addition to which
      drugs should be recommended if necessary during lactation information on use of
      specific drugs is presented in this article. With knowledge of the principles of
      drug passage into breast milk, the goal of the pharmacist should be to minimize
      the infant's exposure to drugs while supporting the mother's desire to continue
      breast-feeding.

PMID- 9519652
TI  - New asthma guidelines: applications for pharmaceutical care.

PMID- 9519654
TI  - Asthma management initiated by community pharmacists improves outcomes: two case
      reports.

PMID- 9519655
TI  - Pharmacy-based diabetes management: a practical approach.

PMID- 9519653
TI  - Long-term management of asthma.

PMID- 9519656
TI  - 1997 Remington Lecture. Re-visioning the profession.

PMID- 9519657
TI  - Vaccination against cancer.

PMID- 9519659
TI  - Integrating complementary medicine?

PMID- 9519658
TI  - Pica.
AB  - Pica is the compulsive eating of non-food substances over a sustained period of
      time. It remains an intriguing, little understood occurrence, with a potential
      for both positive and negative outcomes. In this review information is given on
      the history of the phenomenon, its prevalence among children and women, and its
      relation to iron and zinc deficiency. A number of examples of pica practice are
      reported from Africa.

PMID- 9519660
TI  - Complementary medicine--some definitions.

PMID- 9519661
TI  - Do the homeless get a fair deal from general practitioners?
AB  - Many studies have indicated the health status of homeless people to be typically
      poorer than that of the general population, with various studies indicating a
      high prevalence of psychiatric illness, drug or alcohol misuse and associated
      socio-medical problems. The Bristol Primary Healthcare Project is an agency which
      was established to provide a local health care service tailored to the needs of
      people who are homeless. The present study was carried out as part of an
      evaluation of the service offered locally to homeless people by General
      Practitioners (GPs). A postal questionnaire survey of 155 general practices
      within the Avon FHSA area was carried out. Both fundholding and non-fundholding
      practices were included, within an area including inner city, urban and
      rural/semi-rural locations. One hundred and seventeen completed questionnaires
      were returned, providing a response rate of 75%. Twenty-seven percent of
      practices would fully register a homeless person who seeks to register at the
      practice, 24% would treat as immediate and necessary and 33% would treat as a
      temporary resident. Four percent of fundholding practices surveyed would fully
      register homeless persons and 55% of inner city practices would do so. Seventy
      nine percent of doctors indicated that homeless patients were more difficult to
      treat than other patients. The most frequent problems associated with registering
      homeless persons were perceived to be the associated social problems (90% of
      respondents agreed), the lack of medical records (88% agreed), the complex health
      problems (79% agreed) and the associated alcohol or substance misuse (78%
      agreed). The study has highlighted a need for government to consider providing
      incentives to GPs to register homeless people without resulting in adverse
      effects on their contract targets. The reluctance of some practices to register
      these patients varied by area and type of practice with doctors at fundholding
      practices being the most reluctant. There is an identified need for further
      health education and promotion work and initiatives exemplified by the Bristol
      Primary Healthcare Project for people who are homeless.

PMID- 9519662
TI  - Nurses' evaluations of sources of information about HIV and AIDS.
AB  - Reviews of the literature indicate that nurses feel ill-informed about HIV/AIDS
      and that poor knowledge is associated with anxiety and negative attitudes towards
      infected patients and their care. Although some studies have sought to identify
      the sources of HIV/AIDS information available to nurses, few have attempted to
      understand how nurses evaluate such sources. In this study in 1992, 15 sources of
      HIV/AIDS information were identified during group discussions with nursing staff
      and nurse tutors. 277 nursing staff evaluated each of the sources in terms of
      perceived frequency (how often the source is used) and six items chosen to assess
      the usability and usefulness of each source (e.g. how informative the source is,
      how easy it is to understand). The results indicate that in-service training,
      basic training and professional colleagues are the sources evaluated most highly
      while posters and advertisements, television and radio and popular newspapers are
      the most frequently used sources of information. Trades unions' journals and
      pamphlets are the least frequently used sources of information and receive only
      modest evaluations. 20% of respondents report never having received any training
      regarding HIV and AIDS. Implications for the future provision of HIV/AIDS
      information and directions for further research are discussed.

PMID- 9519663
TI  - Lessons to be learned: a case study approach. Vitamin B12 deficiency of
      nutritional origin.
AB  - The case is presented of a 14 year old boy who developed severe anaemia at the
      onset of puberty caused by nutritional deficiency of vitamin B12 of about 10
      years duration. The dietary intake comprised mainly chips, ice-cream, fruit and
      Coca-Cola--with small amounts of vitamin B12 from occasional slices of chicken
      meat. His denial of abnormal nutritional intake, supported by his mother, delayed
      confirmation of the correct diagnosis. However, the true situation was eventually
      confessed--and following implementation of a normal diet he rapidly improved
      clinically, the haemoglobin value rose to normal and he subsequently remained
      well.

PMID- 9519664
TI  - Assessment of the functional status of elderly subjects in Qassim region, Saudi
      Arabia.
AB  - A cross-sectional study was carried out on a sample of elderly subjects aged 65
      years and above, resident in Qassim region, in central Saudi Arabia. The sample
      size was 266 subjects (12%). The study objective was to assess the subjects'
      functional activities in the form of Activities of Daily Living (ADL) and
      Instrumental Activities of Daily Living (IADL). Wadu, the Muslim tradition of
      washing before the main five daily prayers was included in the ADL. The results
      showed that impairment of ADL, ADL and Wadu, and IADL was observed in 12.4%, 7.9%
      and 54.4% of subjects. Advancing age and female gender were found to be
      negatively, while male gender and having an occupation were found to be
      positively associated with functional activity.

PMID- 9519665
TI  - Roof water collection systems in some Southeast Asian countries: status and water
      quality levels.
AB  - There is extensive use of simple and inexpensive roof water collection systems in
      some Southeast Asian countries. The collected runoff which flows off different
      types of roofs is affected not only by the inherent quality of the roofing
      material but also by the contamination of roofs by rodents, birds, etc.
      Consequently, bacteriological quality levels are excessive though the collected
      rainwater is still used extensively for potable purposes. From samples collected
      in most locations, there were positive Total and Faecal Coliform counts though,
      in terms of physico-chemical parameters, roof water appears to be of a higher
      quality. Various causes have been attributed to the frequent presence of Faecal
      Coliform but, mostly, pollution is of animal origin as the Faecal Coliform/Faecal
      Streptococci ratio is less than unity. It is proposed that the collected roof
      water be boiled, disinfected with household bleach or be subjected to radiation
      from sunlight which appears to have good potential to be an effective
      bactericide. It is recommended that simple testing methods be developed and
      health education imparted to the various aspects of utilising roof water
      collection systems.

PMID- 9519666
TI  - Essential oils and 'aromatherapy': their modern role in healing.
AB  - 'Aromatherapy' is one of the most actively growing forms of alternative medicine
      combining massage together with counselling and a nice odour. Most clients suffer
      from some kind of stress-related disorder and aromatherapy encourages the healing
      process largely through relaxation and the relief of stress. Stress is also a
      major problem in hospitals, hospices and homes for the aged and physically or
      mentally-challenged. Aromatherapy is welcomed by nurses who want to be closer to
      their patient and doctors who can refer patients with stress-related disorders
      who do not respond to conventional medicines. The actual mode of action of
      essential oils in vivo is still far from known, although there is strong in vitro
      evidence that essential oils can act as an antimicrobial or antioxidant agent or
      have a pharmacological effect on various tissues. Studies have shown that
      essential oils have an effect on brainwaves and can also alter behaviour. It is
      possible that most of the effect of the oils is probably transmitted through the
      brain via the olfactory system. Used professionally and safely, aromatherapy can
      be of great benefit as an adjunct to conventional medicine or used simply as an
      alternative.

PMID- 9519667
TI  - The Food Standards Agency.

PMID- 9519668
TI  - Contact dermatitis--the preventable disease.

PMID- 9519669
TI  - The thyroid gland and the law.

PMID- 9519670
TI  - Health effects of indoor combustion products.

PMID- 9519671
TI  - The 'other' sexually transmitted diseases: a case for public health education.
AB  - Generally, people tend to associate the phrase 'sexually transmitted diseases'
      (STDs) with only gonorrhoea and syphilis. This paper highlights the prevalence of
      other diseases such as herpes simplex, trichomoniasis and candidiasis which are
      also sexually transmitted. It is shown that, although they are rarely discussed
      and reported, various estimates, particularly in the developed countries where
      statistics are available, indicate that their incidence rates are rapidly rising
      to epidemic proportions and, in certain instances, have surpassed the annual
      cases of syphilis and gonorrhoea. Their causative organisms, mode of spread,
      signs and symptoms, complications, prevention and control are presented. Although
      knowledge of the above are important, it is emphasised that it is much more
      desirable to focus on prevention through public health education. Health
      education strategies such as avoiding sexual exposure with infectees, personal
      hygiene, simulation, role-play and unemotional discussion in schools and the use
      of mass media in disseminating information to the public regarding prevention,
      control and how to seek for treatment are elaborated upon.

PMID- 9519672
TI  - The influence of smoking habits on thyroid gland volume: an ultrasonic approach.
AB  - The effects of smoking habits on thyroid function, echo-texture (nodules and/or
      cysts) and thyroid gland volume were determined by using ultrasound and measuring
      serum Thyroxin (T4), Triiodothyronine (T3), Thyrotropin (TSH) and TPO antibodies
      (ab-TPO) in 189 healthy smokers and non-smokers, randomly selected (111 females
      and 78 males) among the employees of our hospital and their relatives. When the
      entire group of subjects was considered the mean ratio of thyroid gland
      volume/body weight was found to be significantly higher in male (P < 0.05) and
      female (P < 0.05) smokers compared with non-smokers. In female smokers, mean
      serum thyroid-stimulating hormone (TSH) was lower (P < 0.05) and the degree of
      smoking was positively correlated with the ratio of thyroid gland volume/body
      weight (P < 0.05). However, when the subjects with a family history of goitre in
      first degree relatives were excluded from our study (14 females and 9 males), no
      significant differences in mean ratio of thyroid volume/weight or TSH between the
      remaining smokers and non-smokers were detected. In both sexes, the correlation
      between the degree of smoking and thyroid volume, although positive, did not
      reach statistical significance. No difference in prevalence of abnormal
      echogenicity and echo-texture (nodules and cysts) between smokers and non-smokers
      was detected. It is concluded that smoking habits present a goitrogenic effect
      only in subjects with a family history of goitre but have no influence on thyroid
      gland texture.

PMID- 9519673
TI  - A baseline study of tobacco use among the staff of Aligarh Muslim University,
      Aligarh, India.
AB  - A cross-sectional study of 2,439 university employees and research scholars was
      carried out using the questionnaire method. The objective was to assess the
      prevalence and type of tobacco usage and to collect background data for planning
      health education programmes. The overall prevalence of tobacco usage was 51.5%
      among males and 30.3% among females. There were no female smokers, the preferred
      habit of tobacco usage among women being chewing. The prevalence of smoking among
      non-teaching staff members was significantly higher. Among females, the
      prevalence of tobacco chewers was higher in non-teaching staff members. Tobacco
      usage (both smoking and usage of other forms) rose with age. However, even at 20
      30 years of age 25.4% of males were addicted to smoking. A majority of 60.6% had
      smoked for more than 10 years. Among the staff members (both teaching and non
      teaching) the reason for smoking was either to relax or because of addiction,
      whereas the research scholars smoked to improve their image or for
      enjoyment/pleasure. The reasons given by users of other forms of tobacco were
      boredom, to pass the time or for no reason at all. Among non-users, the majority
      were aware of the harmful effects of smoking. Family pressure and traditions were
      also important reasons for not smoking. The study provides a clear picture of
      tobacco usage within the University.

PMID- 9519674
TI  - Overdose among youth in Bahrain: psycho-social characteristics, contact with
      helping agencies and problems.
AB  - A one year cohort of 67 overdose attempts among youth (15-24 years) was examined
      as part of a case control study. The prevalence rate of 105 per 100,000
      population is lower than reported rates in the West but higher than those for the
      region. The majority of attempters were females and nationals who used
      paracetamol, and their suicide intent was low. Thirteen percent visited a helping
      agency in the previous week and 18% in the previous month. The most common
      difficulties preceding the overdoses were problems with parents, school or work,
      social isolation and problems with boyfriends, or girlfriends respectively.
      Adjustment disorder was the most common diagnosis followed by depression. A
      seasonal variation was noted with 46% of the cases occurring in the summer
      months. The implications of these findings with respect to future policy making
      and prevention were discussed.

PMID- 9519675
TI  - Lessons to be learned: a case study approach. Severe hypoglycaemia in insulin
      dependent diabetes mellitus (IDDM)--living to tell the tale.
AB  - The case is presented of a 62 year old doctor with insulin-dependent diabetes
      mellitus (IDDM) who experienced severe nocturnal hypoglycaemia following a total
      intake for the day of fruit and yoghurt (providing 230 kcal) for breakfast, four
      pints of beer (providing 540 kcal-which included the energy from 37.0 g
      carbohydrate) later in the day and an evening meal containing approximately 123 g
      of carbohydrate (providing 1050 kcal). He had taken insulin, as was his custom,
      just before breakfast, half-an-hour prior to the evening meal and again two-and-a
      half hours afterwards. He felt entirely well when he retired to bed at 2100 h. He
      awoke later, having dreamt that he was practically immobile-but then found to his
      horror that the dream was true. He soon realised that he was severely
      hypoglycaemic and, as he had no glucose immediately available, had no alternative
      but in some way to attempt the journey to the kitchen where there was non-diet
      mandarin drink available in tin cans inside a refrigerator. He was able later to
      recall and, in consequence, describe the whole terrifying experience in great
      detail, on account of the remarkable preservation of mental clarity. The clinical
      features of the episode are viewed in terms of the relationships between alcohol
      intake, carbohydrate ingested and the insulin administered. Exercise was minimal
      on this day.

PMID- 9519676
TI  - Knowledge and misconceptions about malaria among secondary school students and
      teachers in Kassala, eastern Sudan.
AB  - This study reports the responses of high secondary school students and teachers
      to a questionnaire on their knowledge and misconceptions about malaria. Knowledge
      about symptoms and cause of malaria seems to be adequate. However, there were
      deficiencies regarding knowledge of the seriousness of malaria in primigravidas
      and children. There was an exaggerated belief that chloroquine may cause
      abortion. There were also important misconceptions regarding the causation of
      malaria by the plant Unkoleeb (sorghum saccharatum), the belief that the local
      beverage Aradaib (Tramindus indica) cures malaria, as well as beliefs that
      chloroquine injections are more effective than tablets, that intravenous fluids
      are essential for treatment of every attack, and that multi-vitamins may prevent
      the disease. The study throws light on areas where health education should be
      focused.

PMID- 9519677
TI  - Are Saudi female college students prepared for successful breastfeeding?
AB  - A cross-sectional study was carried out on a sample of 285 female students from
      the Science and Arts tracks of the Dammam College for Girls in Eastern Province,
      Saudi Arabia. A self-administered questionnaire was answered by the girls to
      determine whether Saudi female college students were prepared for successful
      breastfeeding, and to assess their knowledge about relevant aspects of
      breastfeeding. The questionnaire contained questions about time of first feed,
      frequency of breastfeeding, duration of a feed and duration of breastfeeding.
      Correct answers were made by 38%, 33%, 35% and 59% of the students respectively.
      Those with a high knowledge score who would breastfeed in the future were
      significantly more than those with a lower knowledge score (p < 0.001). When the
      knowledge score and seven other variables were entered into a logistic regression
      model, knowledge was found to be the only significant predicting factor for the
      decision to breastfeed in the future. The study showed that the attitude of young
      Saudi women is favourable towards breastfeeding. However, they do not seem to be
      prepared to breastfeed so successfully. Knowledge was the only predictory factor
      for the decision to breastfeed in the future. An educational programme may
      increase the prevalence of breastfeeding in this community.

PMID- 9519678
TI  - The maintenance of health during radiotherapy: a nursing perspective.

PMID- 9519679
TI  - Re: Essential oils and 'aromatherapy': their role in healing.

PMID- 9519680
TI  - Re: Food Standards Agency.

PMID- 9519681
TI  - Re: Multiple vaccination.

PMID- 9519682
TI  - Pituitary adenomas in the old-aged.
AB  - From 1986 to 1996, 187 patients with pituitary adenoma were diagnosed and
      received surgery at Kaohsiung Medical College Hospital. Of which, 29 patients
      older than 60 years were retrospectively studied. Their initial clinical
      symptoms, pathological findings, immunoperoxidase staining, electronic
      microscopic findings and hormone levels were retrospectively recorded. We found
      that the old patients more often suffered from the neurological deficit such as
      headache and visual problems rather than endocrine of the tumors cells are
      compared, and fewer cells and nuclei are found in the older group than that in
      the younger group. The secretary granules in functioning tumors especially
      prolactinomas in old-aged patients are larger than those in the young patients.
      The tumor cells in the old-aged patients have fewer subcellular organelles and
      secretary granules but have large secretary granules. It is concluded that: (1)
      transsphenoidal surgery is feasible and safe in this age group; (2) plurihormonal
      tumors occur more frequently in old-age than young patients; (3) clinically
      endocrine-inactive pituitary adenomas occur more often in old-aged; (4) pituitary
      adenomas in old-aged cause neurological deficit more frequently than endocrine
      disturbance.

PMID- 9519683
TI  - Effect of vitamin E, topical hypothermia and steroid on ischemic liver in rats.
AB  - Major hepatic surgery often requires temporary occlusion of the porta hepatis in
      order to minimize intraoperative bleeding. Occlusion of porta hepatis induces
      hepatic ischemia and may cause liver damage. This study was conducted to evaluate
      the effects of vitamin E, topical hypothermia and administration of steroids on
      ischemic liver by assessing the hepatic levels of lipid peroxides and examining
      the ultrastructural change of mitochondria. One hundred and twenty male wistar
      rats were divided into four groups, each of 30. All rats underwent laparotomy and
      the liver ischemia experiment was conducted by clamping the porta hepatis for 15
      minutes. Group A received no further treatment, group B received vitamin E
      (30IU/Kg/B.W) supplementation for one week before experiment, group C was
      topically cooled and group D received preocclusion intravenous methylprednisolone
      (2mg/Kg/B.W). Hepatic lipid peroxides, expressed as nmol MDA/g wet wt were
      assessed by spectrofluorometric methods, and were measured immediately before
      occlusion, 15 min after occlusion, and 15 min after reperfusion. The results
      showed that the concentration of lipid peroxides increased markedly after
      occlusion of porta hepatis in group A, which received no treatment in ischemic
      liver (8.76 +/- 3.19 vs. 10.49 +/- 3.35 MDA nmol/g wet wt, p < 0.05, paired t
      test), while the concentrations of hepatic lipid peroxides were not found to
      increase in groups B, C or D. In the meantime, the ultrastructural study showed
      marked swelling of mitochondria in ischemic liver of group A rats only. This
      suggests that vitamin E supplementation, topical hypothermia and administration
      of steroids will inhibit the propagation of lipid, peroxidation and provide
      protective effects on liver parenchyma during ischemia.

PMID- 9519685
TI  - Ultrasound-guided percutaneous transhepatic drainage of gallbladder followed by
      cholecystectomy for acute cholecystitis--10 years' experience.
AB  - Acute cholecystitis is a common disease which may carry the risk of
      complications, including empyema, perforation, abscess, peritonitis and sepsis.
      Percutaneous transhepatic drainage of the gallbladder (PTGBD) with antibiotics
      can provide prompt decompression of gallbladder in acute cholecystitis and
      interrupt the natural history of the disease effectively. From July 1986 to June
      1996, 154 patients with acute cholecystitis were reviewed retrospectively in
      Kaohsiung Medical College Hospital. The chief symptoms and signs were pain
      (98.1%), fever (57.1%) and jaundice (37.7%). WBC count more than 10,000 was noted
      in 116 (75.3%) patients. Associated diseases included empyema: 42 (27.3%), septic
      shock: 14 (9.1%), diabetes mellitus: 13 (8.4%), pancreatitis: 10 (6.5%),
      perforation: 7 (4.5%), liver cirrhosis: 6 (3.9%) and respiratory failure: 1
      (0.6%). All of them underwent ultrasound-guided PTGBD immediately after the
      diagnosis was established. The symptoms and signs disappeared soon after this
      procedure. Bacterial culture was found positive in 104 (67.5%) of 154 patients in
      which Escherichia coli (51.9%) was the most common organism, followed by
      Klebsiella pneumonia (20.2%). After acute stage, 138 patients obtained the
      cholangiography via PTGBD tube. Gallbladder stones were only noted in 56 (40.6%)
      patients, gallbladder stone concomitant with common bile duct stone in 26
      (18.8%), cystic duct obstruction in 25 (18.1%), acalculous cholecystitis in 21
      (15.2%), gallbladder perforation in 1 (0.7%), choledochocyst in 1 (0.7%), and
      cholecystocolonic fistula in 1 (0.7%). There were 135 patients to undergo surgery
      after the clinical condition was stable. The operative findings included
      gallbladder stones only in 88 (65.2%), gallbladder stone concomitant with common
      bile duct stone in 34 (25.2%), acalculous cholecystitis in 13 (9.6%),
      choledochocyst in 1 (0.7%), and cholecysto-colonic fistula in 1 (0.7%). The
      postoperative complications included wound infection 8 (5.9%), UGI bleeding 3
      (2.2%), acute renal failure 1 (0.7%) and acute respiratory failure 1 (0.7%). The
      postoperative mortality rate was 0.7% (1/135), which was much lower than those of
      previous reports, which not undergoing PTGBD initially. It led us to conclude
      that PTGBD, as an initial preoperative modality to treat acute cholecystitis, is
      effective in decreasing postoperative morbidity and mortality.

PMID- 9519686
TI  - Electron microscopic study on the outer membrane of chronic subdural hematoma.
AB  - We studied the electron microscopic features of the outer membrane of chronic
      subdural hematoma to explore the mechanism of growth of chronic subdural
      hematoma. Ultrastructurally, the outer membrane consisted of bundles of collagen
      fibrils and cellular elements such as fibroblasts, mast cells, migrating
      erythrocytes, platelets and eosinophils. A large number of proliferating
      macrocapillaries coursed among them. Such general characteristics of the
      endothelial cells with proliferating macrocapillaries as gap junctions and
      thinness or absence of the basement membrane suggested that they be very fragile
      and susceptible to bleeding. The number and extent of endothelial gap junctions
      indicated that they could account for most of the leakage not only into the
      tissue of the outer membrane but also into the hematoma cavity. The outer
      membranes had a prominent infiltration of eosinophils. Plasminogen secreted by
      the eosinophils inhibits the formation of platelet thrombus within the lumen and
      also dissolves fibrinoid substance, which reinforces fragile endothelial walls or
      edematous interstitium. These features possibly contribute to the recurring
      hemorrhage from the vessels in the outer membrane and the resultant enlargement
      of the hematoma.

PMID- 9519684
TI  - Preparation and pharmacological evaluation of physostigmine-loaded
      polyisobutylcyanoacrylate nanoparticles in rats.
AB  - The nanoparticles of physostigmine were prepared by an emulsion polymerization of
      polyisobutylcyanoacrylate. The drug content, release and particle size
      distribution of the nanoparticles were characterized. In vitro drug release
      profiles displayed a retardation by the nanoparticles in comparison to the
      aqueous solution. Pharmacological evaluation of physostigmine nanoparticles in
      vivo were carried out with Sprague-Dawley rats. The endogenous acetylcholine was
      sampled by on-line microdialysis and determined by a sensitive microbore HPLC/ED
      system in the striatum of rats. The choline oxidase and catalase immobilized
      enzyme reactors were used as the pre-column to erase choline. Accordingly, this
      chromatographic flow sequence could be utilized for the quantitative assay of
      acetylcholine without interference. The results indicate that the increase of
      acetylcholine (%) in the rats striatum by the nanoparticle was 2.3 times (AUC)
      higher than that of aqueous solution.

PMID- 9519687
TI  - Surgical treatment for pilon fracture of the ankle-open reduction and internal
      fixation.
AB  - From 1991 to 1994, 39 ankles of 38 patients underwent surgical open reduction and
      internal fixation for pilon fractures. These patients included 29 males and 9
      females with an average age of 38.6 y/o (range 28 y/o-58 y/o). The follow up and
      evaluation period averaged 31.7 months (range 22Ms-44Ms), during which time a
      standing x-ray for arthrosis grading and functional scale was used for clinical
      evaluation. Complications included 1 case of infection, 1 case of loss reduction,
      2 cases of partial skin necrosis and 2 cases of delayed union. Post-traumatic
      arthritis occurred in 23 ankles (59%) but only 4 ankles of grade 4 arthrosis
      resulted in poor functional scale and the overall satisfactory rate was 82%. It
      was found that anatomic reduction, rigid fixation and early motion exercise are
      important to successful treatment of ankle fractures. Regarding pilon fracture,
      specifically the severity of fracture pattern and delay of reduction are
      important problems to overcome to ensure successful results. Therefore, adequate
      surgical approach for entire view of ankle joint, reduction and fixation of
      fibula, sufficient bone graft for articular support, intraoperative x-ray check
      and postoperative immobilization are essential for the achievement of better
      clinical results.

PMID- 9519688
TI  - Management of labyrinthine fistula in middle ear cholesteatoma.
AB  - Labyrinthine fistula is a complication of chronic otitis media with
      cholesteatoma. Canal wall down tympanoplasty with partial mastoid cavity
      obliteration and complete removal of cholesteatoma matrix was adopted in five
      cases of labyrinthine fistula. The operation resulted in elimination of vertigo.
      Sensory hearing has been saved in two cases. Air conduction hearing improved in
      one case. In three cases whose air conduction deteriorated post-operatively, bone
      conduction worsened in two cases and remained unchanged in one case
      (Tympanoplasty type 0 was performed in the other one case.) During the follow-up
      period, otorrhea improved in all cases and there was no evidence of recurrence of
      cholesteatoma. If the hearing of the other ear is acceptable, we suggest one
      stage canal wall down tympanoplasty with complete removal of cholesteatoma matrix
      and partial mastoid cavity obliteration. It provides low recurrence rate of
      cholesteatoma and there is no need of re-operation.

PMID- 9519690
TI  - Anticardiolipin antibody-related Budd-Chiari syndrome: report of a case.
AB  - We report a case of a 37-year-old female who suffered from upper abdominal pain,
      progressive abdominal distention, shortness of breath, palpitation and pitting
      edema of lower legs for more than one month. Abdominal sonography showed small
      caliber of hepatic veins, mild hepatosplenomegaly and moderate ascites. Computed
      tomography of abdomen disclosed extensive thrombi in bilateral femoral veins,
      ovarian veins and inferior vena cava. Ascites was transudate with normal cell
      count. Laboratory data showed hypoalbuminemia, mild elevation of total bilirubin
      and iron deficiency anemia. Anti-cardiolipin antibody was positive and
      antinuclear antibody was negative. The histopathological features, including
      sinusoidal dilatation with atrophic change of adjacent hepatocytes, slight
      congestion and hemosiderin-like material within the cytoplasm of Kupffer cells,
      were compatible with the criteria of Budd-Chiari syndrome. Heparin was
      intravenously administered immediately to prevent further progression of
      thrombosis. The ascites was successfully controlled with diuretics
      (spironolactone and furosemide). After a two-week course of treatment, she was
      discharged in good condition and on warfarin anti-coagulant medication.

PMID- 9519689
TI  - Reflex sympathetic dystrophy syndrome in stroke patients with hemiplegia-three
      phase bone scintigraphy and clinical characteristics.
AB  - In an attempt to investigate the correlation between three phase bone
      scintigraphy (TPBS) and the clinical manifestation of reflex sympathetic
      dystrophy syndrome (RSDS) in the upper extremity of hemiplegia, we collected 30
      patients with cerebral vascular accidents (CVA) confirmed by head computed
      tomography (infarction or hemorrhage) within 3 months of their CVA event. All
      patients received TPBS after admission. Clinical assessment for the development
      of the RSDS was done at least 3 months (268 +/- 120 days) after the stroke. The
      correlation between the development of RSD and certain clinical variables
      (including sex, age, side affected, caused of stroke, and motor stage) were
      analyzed. Twelve patients (40%) manifested definite or probable RSDS, as assessed
      by Tepperman's criteria, during the follow-up period. Nineteen patients (63%)
      exhibited radionuclide evidence of RSDS based on delayed bone scan criteria
      performed within 3 months (43 +/- 25 days) of the stroke. The positive delayed
      image of TPBS demonstrated a sensitivity = 92%; specificity = 56%; positive
      predictive value = 58%, and negative predictive value = 91%. The Kappa statistics
      for agreement between positive bone scan and RSDS development was 70% (Kappa =
      0.43, p < 0.05). Neither sex, age, side affected, cause of stroke, or motor stage
      had a significant correlation with clinical RSDS. In conclusion, TPBS is a useful
      screening tool for the development of RSD in hemiplegic patients. However, the
      diagnosis of RSDS depends on the clinical evaluation and that TPBS as an adjunct
      assessment of RSDS must be interpreted with caution.

PMID- 9519691
TI  - Cleidocranial dysplasia: a rare case associated with congenital hypothyroidism
      and severe neonatal hyperbilirubinemia.
AB  - Cleidocranial dysplasia is an autosomal dominant disorder affecting skeletal
      ossification and tooth development. This disorder can be rarely associated with
      blood, intestinal and vascular anomalies. There has been no case reported in
      previous literature that discusses this disorder in association with congenital
      hypothyroidism and severe neonatal hyperbilirubinemia. Herein, we report on a 4
      year-old boy who in an outpatient clinic was diagnosed as having cleidocranial
      dysplasia, with defective ossification over bilateral hypoplastic clavicles,
      narrowed thoracic cage on chest x-ray and prominent wormian bones over the
      lambdoid sutures on skull x-ray. Physical examination revealed a 4-fb wide open
      anterial fontanel, frontal bossing and malalignment of teeth. He was a primpara
      with birth weight of 2350 gm and gestation age of 33 weeks. He had received blood
      exchange transfusion on the 4th postnatal day at Ping-Tong Christian Hospital
      because of severe neonatal hyperbilirubinemia. Congenital hypothyroidism was
      diagnosed on the 10th day. He was then treated with thyroxine and transferred to
      our hospital. Thyroid scan revealed diffusely decreased radioactivity in
      bilateral lobes of the thyroid gland. According to out clinic findings at his
      regular follow ups, with continued use of thyroxine supplement, he now has a
      normal thyroid function and has a body length of about 50 percentile.

PMID- 9519692
TI  - ATRA-induced pseudotumour cerebri--one case report.
AB  - A 17-year-old girl with acute pomyelocytic leukemia (APL) went into complete
      remission following Daunorubicin, Ara-C and ATRA chemotherapy for 1 month.
      Unfortunately, prolonged administration of ATRA 6 weeks later caused binocular
      diplopia with left abducent nerve paresis, which gradually disappeared upon
      withdrawal of ATRA. We propose that it is ATRA induced pseudotumour cerebri and
      present this case to discuss the relationship between the ATRA and pseudotumour
      cerebri.

PMID- 9519694
TI  - Imagination inflation for action events: repeated imaginings lead to illusory
      recollections.
AB  - In two experiments, subjects heard simple action statements (e.g., "Break the
      toothpick"), and, in some conditions, they also performed the action or imagined
      performing the action. In a second session that occurred at a later point (10
      min, 24 h, 1 week, or 2 weeks later), subjects imagined performing actions one,
      three, or five times. Some imagined actions represented statements heard,
      imagined, or performed in the first session, whereas other statements were new in
      the second session. During a third (test) phase, subjects were instructed to
      recognize statements only if they had occurred during the first session and, if
      recognized, to tell whether the action statement had been carried out, imagined,
      or merely heard. The primary finding was that increasing the number of imaginings
      during the second session caused subjects to remember later that they had
      performed an action during the first session when in fact they had not
      (imagination inflation). This outcome occurred both for statements that subjects
      had heard but not performed during the first session and for statements that had
      never been heard during the first session. The results are generally consistent
      with Johnson, Hashtroudi, and Lindsay's (1993) source monitoring framework and
      reveal a powerful memory illusion: Imagining performance of an action can cause
      its recollection as actually having been carried out.

PMID- 9519693
TI  - Things learned in early adulthood are remembered best.
AB  - Evidence is reviewed that for older adults the period from 10 to 30 years of age
      produces recall of the most autobiographical memories, the most vivid memories,
      and the most important memories. It is the period from which peoples' favorite
      films, music, and books come and the period from which they judge the most
      important world events to have originated. Factual, semantic, general-knowledge,
      multiple-choice questions about the Academy Awards, the World Series, and current
      events from this period were answered more accurately by two different groups of
      30 older adults tested 10 years apart. A cognitive theory based on the importance
      of transitions and several noncognitive theories are considered as explanations
      of this pervasive phenomenon.

PMID- 9519695
TI  - Reading "glasses" will prime "vision," but reading a pair of "glasses" will not.
AB  - In a lexical decision task with two primes and a target, the target was preceded
      300 msec by the second prime (P2) which in turn was preceded by a brief forward
      and backward masked first prime (P1). When P1 and P2 were unrelated, reaction
      times were faster when the target was related to P2 (e.g., wave SALT ... pepper)
      than when the target was unrelated to P2 (and P1--e.g., wave LOAN ... pepper).
      However, this semantic priming effect was reduced to statistically nonsignificant
      levels when P1 and P2 were repetitions of the same word. That is, priming did not
      occur for salt SALT ... pepper relative to loan LOAN ... pepper. This reduction
      in priming was observed whether P2 and the target were strongly or weakly
      related. These findings raise problems for current accounts of semantic priming.

PMID- 9519697
TI  - When do nonwords activate semantics? Implications for models of visual word
      recognition.
AB  - Three lexical decision experiments examined the conditions in which nonwords
      activate semantics. Lexical decisions to targets (e.g., CAT) were faster when
      preceded by semantically related nonword primes (e.g., DEG derived from DOG) when
      the prime was brief and masked; this nonword priming effect was eliminated when
      the prime was presented for a longer duration. These results are discussed in the
      context of both parallel distributed processing models and the idea that the
      occurrence of nonword priming depends upon subjects being unable to verify the
      identity of the prime.

PMID- 9519696
TI  - The effects on priming of word frequency, number of repetitions, and delay depend
      on the magnitude of priming.
AB  - Conflicting findings with respect to the effects of experimental manipulations on
      priming have been reported in previous studies. It is argued that, in many
      priming tasks, large amounts of task-relevant information are available from
      various sources, and that, therefore, the information available from a specific
      study episode will have only a small impact on overall performance level. Under
      such circumstances, high levels of baseline performance and small priming effects
      will be observed. The experiments reported here investigated the hypothesis that
      a high baseline performance in information-processing tasks that are used to
      measure priming may constrain priming effects. In a series of word-naming
      experiments, perceptual difficulty and, therefore, baseline performance was
      manipulated. Under easy conditions, priming effects were relatively small and
      were not affected by word frequency, spaced repetition, or delay. Under more
      difficult conditions, priming effects were larger, and significant effects of all
      of the above-mentioned experimental manipulations were observed. Under conditions
      that produced the largest priming effects, a significant relationship between
      priming and explicit-memory performance could be observed. In the last
      experiment, it was shown that the characteristics of the retrieval task can
      substantially affect the magnitude of priming. It is argued that priming effects
      should be considered to reflect interactions between memory traces and the
      information-processing components of the priming task.

PMID- 9519698
TI  - Orthography and phonology in reading Japanese kanji words: evidence from the
      semantic decision task with homophones.
AB  - Correspondences between spelling and sound for Japanese kanji are complex and
      deep. The meaning of kanji words has generally been assumed to be accessed
      directly from orthography without phonological mediation. Experiment 1, however,
      replicated the findings of Van Orden (1987) that subjects made more false
      positive errors on homophone foils than they did on nonhomophone controls in a
      semantic decision task, although they did so only when the foils were
      orthographically similar to the correct exemplars, which indicates both
      orthographic and phonological activations of meaning. Experiment 2 showed the
      same results when subjects were not required to pronounce the target words after
      semantic decisions, which indicates automatic phonological activation of kanji
      words. In Experiment 3, under pattern-masking conditions, this homophony effect
      was reduced but remained on errors, and the orthographic-similarity effect
      remained strong on both homophone and nonhomophone foils. These results suggest
      that both orthography and phonology play an important role in the comprehension
      of kanji words.

PMID- 9519699
TI  - Linearization strategies during language production.
AB  - The two experiments reported here were designed to examine discourse planning
      during language production. Following the work of Levelt (1981, 1982),
      participants were shown simple networks consisting of two branches, and their
      task was to describe the networks. The two branches of the networks differed in
      either length or complexity; the dependent measure was participants' decisions to
      describe the left or right branch first. The experiments showed that speakers
      preferred to describe a less complex branch before a more complex branch and
      preferred to describe a shorter branch before a longer branch. Levelt's minimal
      load principle is invoked to explain these results, along with the principle of
      incrementalism (Levelt, 1989). Discussion focuses on the possibility that
      incrementalism in production is useful to both the speaker and the listener.

PMID- 9519700
TI  - Memory for locations within regions: spatial biases and visual hemifield
      differences.
AB  - Memory for location of a dot inside a circle was investigated with the circle in
      the center of a computer screen (Experiment 1) or with the circle presented in
      either the left or the right visual field (Experiment 2). In both experiments, as
      in Huttenlocher, Hedges, and Duncan's (1991) study, the task was to relocate the
      dot by marking the remembered location. When errors in angular and radial
      estimates were considered separately, it was found that, in both experiments, the
      angular locations of estimates of the dots' positions regressed toward different
      locations inside each quadrant of the circle; the radial locations of the
      estimates of dots' positions tended to regress toward locations near the
      circumference. These variations in the direction of bias appeared to reflect a
      general shift of estimates toward the upper left arc of the circle. The second
      experiment replicated the preceding effects but also revealed that the
      regressions within quadrants of angular values were stronger after right visual
      field that after left visual field presentations. We interpret the dissociation
      between visual fields as evidence that memory for categorical spatial relations
      (Kosslyn, 1987) is more dependent on left-hemisphere than on right-hemisphere
      processing.

PMID- 9519701
TI  - Distinctiveness effects in recall: differential processing or privileged
      retrieval?
AB  - Unusual information is generally recalled better than common information (the
      distinctiveness effect). Differential processing accounts propose that the effect
      occurs because unusual material elicits encoding processes that are different
      from those elicited by common material, and strong versions of these accounts
      predict distinctiveness effects in between-list as well as within-list designs.
      Experiment 1 employed a between-list design and manipulated presentation rate.
      Contrary to differential processing predictions, no distinctiveness effect
      emerged, nor did recall patterns for atypical versus common sentences differ as a
      function of presentation rate. Experiment 2 further tested differential
      processing accounts as well as representation accounts via a within-list
      manipulation and conditions that included experimenter-provided elaborations.
      Distinctiveness effects emerged in all conditions and, contrary to differential
      processing predictions, the pattern of recall in the elaborated conditions did
      not differ from that in the unelaborated conditions. Taken together, the results
      of this study lend more support to a representation view that suggests mechanisms
      related to the representation and subsequent retrievability of elements in the
      memory record play a major role in the distinctiveness effect.

PMID- 9519702
TI  - Prospective remembering: perceptually driven or conceptually driven processes?
AB  - Converging experimental operations and several prospective memory tasks were used
      across three experiments to determine the extent to which prospective remembering
      is supported by data-driven versus conceptually driven processes. In all
      experiments, subjects were asked to perform an action when a target item later
      occurred. When the semantic context changed from encoding to test, prospective
      memory significantly declined (Experiment 1). When the target event (the item,
      which in its subsequent appearance in the experiment was the signal to perform
      the action) was presented as word (relative to picture presentation, Experiment
      2) or was encoded nonsemantically (relative to semantic encoding, Experiment 3),
      there was a decline in prospective memory performance. Dividing attention during
      prospective memory retrieval substantially reduced prospective memory performance
      (Experiment 3). The results of this research indicated that prospective memory is
      largely conceptually driven, and it behaves more similarly to direct rather than
      indirect conceptual tests. We suggest that prospective remembering of the type
      studied here is mediated by a reflexive episodic associative memory system as
      proposed by Moscovitch (1994).

PMID- 9519703
TI  - The time-course of the generation effect.
AB  - The generation effect, in which items generated by following some rule are
      remembered better than stimuli that are simply read, has been studied intensely
      over the past two decades. To date, however, researchers have largely ignored the
      temporal aspects of this effect. In the present research, we used a variable
      onset time for the presentation of the to-be-remembered material, thus providing
      the ability to determine at what point during processing the generation effect
      originates. The results indicate that some benefit from generation attempts
      occurs even when subjects have only a few hundred milliseconds in which to
      process the stimulus, but that more of the benefit occurs later. This finding
      suggests that the generation effect results from continuous or multiple discrete
      stages of information accrual or strengthening of memory traces over time, rather
      than from a single discrete increment upon final generation.

PMID- 9519704
TI  - Not guppies, nor goldfish, but tumble dryers, Noriega, Jesse Jackson, panties,
      car crashes, bird books, and Stevie Wonder.
AB  - This paper focuses on the guppy effect (Osherson & Smith, 1981), that is, on the
      existence of examples of conjunctive concepts that are more typical of the
      conjunction than of both constituents. The most frequently given examples of this
      effect, guppy and goldfish, are shown not to be more typical of the conjunction
      pet fish than of fish in two between-subjects and one within-subjects experiment.
      The frequency of the effect in a large empirical study is investigated, and
      better examples of the effect are suggested.

PMID- 9519706
TI  - Who uses base rates and P(D/approximately H)? An analysis of individual
      differences.
AB  - In two experiments, involving over 900 subjects, we examined the cognitive
      correlates of the tendency to view P(D/approximately H) and base rate information
      as relevant to probability assessment. We found that individuals who viewed
      P(D/approximately H) as relevant in a selection task and who used it to make the
      proper Bayesian adjustment in a probability assessment task scored higher on
      tests of cognitive ability and were better deductive and inductive reasoners.
      They were less biased by prior beliefs and more data-driven on a covariation
      assessment task. In contrast, individuals who thought that base rates were
      relevant did not display better reasoning skill or higher cognitive ability. Our
      results parallel disputes about the normative status of various components of the
      Bayesian formula in interesting ways. It is argued that patterns of covariance
      among reasoning tasks may have implications for inferences about what individuals
      are trying to optimize in a rational analysis (J. R. Anderson, 1990, 1991).

PMID- 9519705
TI  - The perception of face gender: the role of stimulus structure in recognition and
      classification.
AB  - The perception of face gender was examined in the context of extending "face
      space" models of human face representations to include the perceptual categories
      defined by male and female faces. We collected data on the recognizability,
      gender classifiability (reaction time to classify a face as male/female),
      attractiveness, and masculinity/femininity of individual male and female faces.
      Factor analyses applied separately to the data for male and female faces yielded
      the following results. First, for both male and female faces, the recognizability
      and gender classifiability of faces were independent--a result inconsistent with
      the hypothesis that both recognizability and gender classifiability depend on a
      face's "distance" from the subcategory gender prototype. Instead, caricatured
      aspects of gender (femininity/masculinity ratings) related to the gender
      classifiability of the faces. Second, facial attractiveness related inversely to
      face recognizability for male, but not for female, faces--a result that resolves
      inconsistencies in previous studies. Third, attractiveness and femininity for
      female faces were nearly equivalent, but attractiveness and masculinity for male
      faces were not equivalent. Finally, we applied principal component analysis to
      the pixel-coded face images with the aim of extracting measures related to the
      gender classifiability and recognizability of individual faces. We incorporated
      these model-derived measures into the factor analysis with the human rating and
      performance measures. This combined analysis indicated that face recognizability
      is related to the distinctiveness of a face with respect to its gender
      subcategory prototype. Additionally, the gender classifiability of faces related
      to at least one caricatured aspect of face gender.

PMID- 9519707
TI  - We are what we repeatedly do.

PMID- 9519708
TI  - Glucagon-like peptides.
AB  - Proglucagon contains the sequence of two glucagon-like peptides, GLP-1 and GLP-2,
      secreted from enteroendocrine cells of the small and large intestine. GLP-1
      lowers blood glucose in both NIDDM and IDDM patients and may be therapeutically
      useful for treatment of patients with diabetes. GLP-1 regulates blood glucose via
      stimulation of glucose-dependent insulin secretion, inhibition of gastric
      emptying, and inhibition of glucagon secretion. GLP-1 may also regulate glycogen
      synthesis in adipose tissue and muscle; however, the mechanism for these
      peripheral effects remains unclear. GLP-1 is produced in the brain, and
      intracerebroventricular GLP-1 in rodents is a potent inhibitor of food and water
      intake. The short duration of action of GLP-1 may be accounted for in part by the
      enzyme dipeptidyl peptidase 4 (DPP-IV), which cleaves GLP-1 at the NH2-terminus;
      hence GLP-1 analogs or the lizard peptide exendin-4 that are resistant to DPP-IV
      cleavage may be more potent GLP-1 molecules in vivo. GLP-2 has recently been
      shown to display intestinal growth factor activity in rodents, raising the
      possibility that GLP-2 may be therapeutically useful for enhancement of mucosal
      regeneration in patients with intestinal disease. This review discusses recent
      advances in our understanding of the biological activity of the glucagon-like
      peptides.

PMID- 9519709
TI  - Expression of glutamine:fructose-6-phosphate amidotransferase in human tissues:
      evidence for high variability and distinct regulation in diabetes.
AB  - Recent in vitro and in vivo studies suggested that the increased flux of glucose
      through the hexosamine biosynthetic pathway may contribute to glucose-induced
      insulin resistance and to the induction of the synthesis of growth factors.
      Because glutamine:fructose-6-phosphate amidotransferase (GFAT) catalyzes the
      first and rate-limiting step in the formation of hexosamine products, this enzyme
      is the key regulator in this pathway and is therefore possibly also involved in
      the alterations occurring in preclinical or manifest diabetic patients. To study
      the expression of GFAT in human tissues, we produced and characterized a peptic
      antiserum specifically recognizing GFAT protein and a riboprobe for the detection
      of GFAT mRNA. Immunohistochemical and nonradioactive in situ hybridization
      analysis revealed high levels of expression of GFAT protein and mRNA in
      adipocytes and skeletal muscle. Furthermore, a marked GFAT expression was found
      in vascular smooth muscle cells with unexpectedly high variability and lower
      levels in other cells, e.g., peripheral nerve sheath cells or endocrine-active
      cells, including the pancreatic islet cell. GFAT protein expression was below
      detection level in endothelium, osteocytes, lymphocytes, granulocytes, and in
      most quiescent fibroblasts. In renal tissue, GFAT was expressed in tubular
      epithelial cells, while glomerular cells remained essentially unstained. Renal
      sections obtained from patients with diabetic nephropathy showed significant GFAT
      expression in some glomerular epithelial and mesangial cells, indicating that
      GFAT expression may be induced by manifest diabetes. Our data indicate that GFAT
      is expressed in most tissues involved in the development of diabetic late
      complications. Furthermore, the results suggest that GFAT gene expression is
      highly regulated.

PMID- 9519710
TI  - Possibility of distinct insulin-signaling pathways beyond phosphatidylinositol 3
      kinase-mediating glucose transport and lipogenesis.
AB  - The aim of this study was to compare the effects of insulin and the
      insulinomimetic agent, englitazone, on functional end points and putative
      mediators of insulin action in 3T3-L1 adipocytes. Cells were incubated with
      englitazone for 48 h or with insulin for 10 or 30 min, or both, and 2-deoxy-D
      [3H]glucose (2DG) uptake and lipogenesis (from [14C]glucose) were measured.
      Tyrosine phosphorylation of the insulin receptor (IR), insulin receptor
      substrates 1 and 2 (IRS-1 and IRS-2), and pp60, and phosphatidylinositol (PI) 3
      kinase activity (using PI as substrate) and mitogen-activated protein kinase
      (MAPK) activity were assayed in cell lysates. Englitazone increased 2DG uptake in
      a concentration-dependent (10-100 micromol/l) manner by up to sixfold, and
      preincubation with englitazone significantly enhanced insulin-stimulated 2DG
      uptake. However, englitazone had a biphasic effect on lipogenesis (163 +/- 13%
      basal at 10 micromol/l vs. 96 +/- 14% at 100 micromol/l), but when acetate was
      used as substrate, only concentration-dependent inhibition of lipogenesis
      occurred. In addition, englitazone decreased insulin-stimulated lipogenesis in a
      concentration-dependent manner. Englitazone did not increase IR, IRS-1/IRS-2,
      pp60, or MAPK phosphorylation, nor did it enhance insulin's stimulation of these
      parameters. Although englitazone alone did not activate PI 3-kinase, it did
      enhance the stimulation of the enzyme produced by a submaximally effective
      insulin concentration. Significant (63%) inhibition of insulin-stimulated
      lipogenesis occurred at a concentration of englitazone (30 micromol/l) that did
      not affect MAPK activation, which suggests that the drug's inhibitory effect on
      lipogenesis is not mediated by this pathway. Englitazone did not affect the
      expression of the peroxisome proliferator response element-containing fatty acyl
      CoA synthase gene, although it cannot be ruled out that expression of other
      lipogenic enzymes are altered by englitazone via peroxisome proliferator
      activated receptor-gamma activation or by an alternate pathway. Thus englitazone
      stimulates 2DG uptake without affecting PI 3-kinase, but it can enhance both
      insulin-stimulated 2DG uptake and PI 3-kinase activity. However, englitazone
      inhibits insulin-stimulated lipogenesis without inhibiting PI 3-kinase activity.
      Assuming activation of PI 3-kinase mediates insulin-stimulated 2-DG and
      lipogenesis, then the signaling pathways for each process diverge beyond PI 3
      kinase.

PMID- 9519711
TI  - The B-subunit of cholera toxin induces immunoregulatory cells and prevents
      diabetes in the NOD mouse.
AB  - The B-subunit of the cholera toxin molecule (CT-B) has T-cell immunomodulatory
      properties. Because the pathogenesis of diabetes in the nonobese diabetic (NOD)
      mouse model of IDDM is thought to be a T-cell-mediated process due to an
      imbalance of immunoregulatory and anti-islet effector cells, we examined the
      effect of CT-B administration on the development of diabetes in the NOD mouse and
      assessed whether this potential diabetes-sparing effect of CT-B is mediated by
      changes in immunoregulatory and/or anti-islet cytotoxic effector cell activity.
      The administration of either intravenous or intraperitoneal CT-B decreased the
      development of diabetes with no apparent drug toxicity. At 6 months of age, only
      18% of CT-B vs. 75% of saline-treated animals had diabetes. Histopathological
      examination revealed less islet atrophy in CT-B-treated animals. The in vitro
      proliferative responses of mononuclear splenocytes and thymocytes to concanavalin
      A and lipolysaccharide and the proportion of B-cells and T-cell subsets were not
      altered by CT-B treatment. CT-B administration did not inhibit the primary
      immunization of mice to tetanus toxoid. The development of diabetes in irradiated
      NOD mice was slower in the animals injected with spleen cells (SC) from CT-B
      treated than from saline-treated NOD mice, suggesting that CT-B decreases anti
      islet effector cell activity. The injection of SC from CT-B-treated mice
      inhibited the adoptive transfer of diabetes by SC from diabetic mice into
      irradiated NOD mice, documenting that CT-B administration induces regulatory cell
      activity. In conclusion, CT-B administration prevents the development of diabetes
      in NOD mice by inhibiting the immune destruction of islets. This islet-sparing
      activity appears mediated, at least in part, by the induction of regulatory cells
      and, in turn, suppression of anti-islet effector cells, which is not associated
      with generalized immunosuppression or T- or B-cell depletion.

PMID- 9519712
TI  - Normoglycemia restores beta-cell replicative response to glucose in transplanted
      islets exposed to chronic hyperglycemia.
AB  - We studied the effects of chronic hyperglycemia on beta-cell replication and mass
      in transplanted (Tx) islets. Five groups of streptozocin-induced diabetic C57Bl/6
      mice were transplanted with 100 (Tx-100) syngeneic islets, an insufficient beta
      cell mass to restore normoglycemia. Groups 1 and 2 remained hyperglycemic
      throughout the study; after 30 days of hyperglycemia, a second transplantation of
      250 islets (Tx-250) restored normoglycemia in groups 3, 4, and 5. Tx-250 was
      harvested on day 60 in all three groups, and transient mild hyperglycemia
      developed (10-12 days); thereafter, Tx-100 maintained blood glucose values in the
      normal range. Tx-100 was harvested 14 (group 1), 60 (groups 2 and 3), 74 (group
      4), and 90 (group 5) days after transplantation. Hyperglycemia increased beta
      cell replication after 14 days (group 1: 1.26 +/- 0.18%, P < 0.05) but not after
      60 days (group 2: 0.59 +/- 0.13%) compared with islets exposed to normoglycemia
      (group 3: 0.51 +/- 0.07%) (analysis of variance [ANOVA], P < 0.0002). beta-cell
      replication in group 4 increased after Tx-250 harvesting (0.94 +/- 0.16%, P <
      0.05). The initially Tx beta-cell mass (0.21 +/- 0.014 mg) was progressively
      reduced in hyperglycemic groups (group 1: 0.13 +/- 0.020 mg; group 2: 0.048 +/-
      0.012 mg; P < 0.05) (ANOVA, P = 0.0001). Restoration of normoglycemia after Tx
      250 did not modify beta-cell mass in Tx-100 grafts (group 3: 0.076 +/- 0.008 mg).
      However, after Tx-250 harvesting, beta-cell mass increased progressively (group
      4: 0.11 +/- 0.018 mg; group 5: 0.14 +/- 0.026 mg, P < 0.05), although it was
      still reduced compared with the initially Tx beta-cell mass (P < 0.05). In
      summary, Tx islets exposed to severe chronic hyperglycemia showed a limited beta
      cell replication and a progressive reduction in beta-cell mass. With
      normoglycemia, the Tx beta-cells recovered the replicative response to glucose
      and partially restored the initially Tx beta-cell mass, indicating that
      normoglycemia, even after long-term hyperglycemia, has a beneficial effect in
      islet transplantation.

PMID- 9519713
TI  - Excessive production of nitric oxide by macrophages from DP-BB rats is secondary
      to the T-lymphopenic state of these animals.
AB  - Activated macrophages are the first mononuclear cells to migrate to the pancreas
      of DP-BB rats at the initiation of insulitis. These cells produce an excess of
      NO, which has been implicated as a mediator of both beta-cell damage and
      inhibition of T-cell proliferation in this rat strain. Genetic studies have shown
      that the impaired proliferative response of T-cells segregates with one of the
      diabetes-susceptibility genes of the DP-BB rat, lyp, which is responsible for a
      peripheral T-lymphopenia. This observation suggests that the dysregulated
      expression of inducible NO synthase (iNOS) is under the control of lyp itself or
      a gene in linkage disequilibrium with lyp. Using two models of hemopoietic
      chimeras--DP-BB rats reconstituted with isocongenic T-cells and irradiated (WF x
      DP-BB)F1 animals reconstituted with bone marrow of both parental strains--we
      demonstrated that the production of NO by DP-BB macrophages is normal when these
      cells originate from a non-T-lymphopenic environment. Consequently, these
      macrophages no longer inhibit the stimulation of DNA synthesis in activated T
      cells. Macrophages of young WF rats were found to produce high levels of NO,
      which inhibited T-cell proliferation in vitro. This observation strongly suggests
      that upregulation of NO synthesis in DP-BB macrophages represents the abnormal
      persistence of a phenomenon restricted to the first few weeks of life in non
      diabetes-prone rats. Taken together, these results demonstrate that the elevated
      production of NO by DP-BB macrophages results from the lyp mutation and
      represents a crucial mechanism through which T-lymphopenia contributes to the
      development of diabetes.

PMID- 9519714
TI  - 4-Hydroxyisoleucine: a novel amino acid potentiator of insulin secretion.
AB  - We report the characterization of a new insulinotropic compound, 4
      hydroxyisoleucine. This amino acid has been extracted and purified from fenugreek
      seeds, which are known in traditional medicine for their antidiabetic properties.
      4-Hydroxyisoleucine increases glucose-induced insulin release, in the
      concentration range of 100 micromol/l to 1 mmol/l, through a direct effect on
      isolated islets of Langerhans from both rats and humans. The stimulating effect
      of 4-hydroxyisoleucine was strictly glucose dependent; indeed, ineffective at low
      (3 mmol/l) or basal (5 mmol/l) glucose concentrations, the amino acid potentiated
      the insulin secretion induced by supranormal (6.6-16.7 mmol/l) concentrations of
      glucose. In addition, in the isolated perfused rat pancreas, we could show 1)
      that the pattern of insulin secretion induced by 4-hydroxyisoleucine was
      biphasic, 2) that this effect occurred in the absence of any change in pancreatic
      alpha- and delta-cell activity, and 3) that the more glucose concentration was
      increased, the more insulin response was amplified. Moreover, 4-hydroxyisoleucine
      did not interact with other agonists of insulin secretion (leucine, arginine,
      tolbutamide, glyceraldehyde). Therefore, we conclude that 4-hydroxyisoleucine
      insulinotropic activity might, at least in part, account for fenugreek seeds'
      antidiabetic properties. This secretagogue may be considered as a novel drug with
      potential interest for the treatment of NIDDM.

PMID- 9519715
TI  - RX871024 induces Ca2+ mobilization from thapsigargin-sensitive stores in mouse
      pancreatic beta-cells.
AB  - The effects of RX871024, a compound with an imidazoline structure, on cytoplasmic
      free Ca2+ concentration ([Ca2+]i) in mouse pancreatic beta-cells were studied.
      RX871024 modulates [Ca2+]i by at least two mechanisms. One mechanism involves
      closure of ATP-regulated K+ channels, resulting in membrane depolarization,
      opening of voltage-gated L-type Ca2+ channels, and a subsequent increase in
      [Ca2+]i. Another mechanism, reported here for the first time, deals with RX871024
      induced mobilization of Ca2+ from nonmitochondrial thapsigargin-sensitive
      intracellular stores. Reduced glutathione, inhibitors of cytochrome P-450, and
      monoaminooxidases A and B blocked this Ca2+ mobilization. It is concluded that
      the mechanism of RX871024-induced Ca2+ mobilization from intracellular stores
      involves changes in the oxidation/reduction state of the pancreatic beta-cell and
      may be controlled by cytochrome P-450.

PMID- 9519716
TI  - Effects of leptin on insulin secretion from isolated rat pancreatic islets.
AB  - Leptin is a hormone secreted by adipocytes as a peripheral metabolic signal for
      the central regulation of energy homeostasis or the reproductive system. Recent
      studies demonstrated that leptin receptor mRNA is expressed in pancreatic islets
      of rodents and that leptin at relatively high doses inhibits glucose-induced
      insulin secretion from rat islets. However, the physiological mechanism of leptin
      on insulin secretion has not been identified. In this study, we report that
      leptin inhibits glucose-induced insulin secretion at lower concentrations ranging
      from 25 to 50 ng/ml using a static incubation method. A perifusion study revealed
      that leptin (50 ng/ml) affected the second phase of insulin secretion but not the
      first phase. Leptin did not affect insulin secretion stimulated by glibenclamide
      (1 and 5 micromol/l) or forskolin (1 micromol/l). Leptin (50 ng/ml) significantly
      inhibited insulin secretion induced by the phorbol ester phorbol 12-myristate 13
      acetate (TPA) in the presence of Ca2+ but not in the absence of Ca2+. Because TPA
      is known to activate protein kinase C (PKC), these present results suggest that
      leptin, at a physiological concentration, suppresses the second phase of insulin
      secretion by reducing activity of the Ca2+-dependent PKC isoform.

PMID- 9519717
TI  - Experimental NIDDM: development of a new model in adult rats administered
      streptozotocin and nicotinamide.
AB  - We took advantage of the partial protection exerted by suitable dosages of
      nicotinamide against the beta-cytotoxic effect of streptozotocin (STZ) to create
      a new experimental diabetic syndrome in adult rats that appears closer to NIDDM
      than other available animal models with regard to insulin responsiveness to
      glucose and sulfonylureas. Among the various dosages of nicotinamide tested in 3
      month-old Wistar rats (100-350 mg/kg body wt), the dosage of 230 mg/kg, given
      intraperitoneally 15 min before STZ administration (65 mg/kg i.v.) yielded a
      maximum of animals with moderate and stable nonfasting hyperglycemia (155 +/- 3
      vs. 121 +/- 3 mg/dl in controls; P < 0.05) and 40% preservation of pancreatic
      insulin stores. We also evaluated beta-cell function both in vitro and in vivo 4
      9 weeks after inducing diabetes. In the isolated perfused pancreas, insulin
      response to glucose elevation (5-11 mmol/l) was clearly present, although
      significantly reduced with respect to controls (P < 0.01). Moreover, the insulin
      response to tolbutamide (0.19 mmol/l) was similar to that observed in normal
      pancreases. Perfused pancreases from diabetic animals also exhibited a striking
      hypersensitivity to arginine infusion (7 mmol/l). In rats administered STZ plus
      nicotinamide, intravenous glucose tolerance tests revealed clear abnormalities in
      glucose tolerance and insulin responsiveness, which were interestingly reversed
      by tolbutamide administration (40 mg/kg i.v.). In conclusion, this novel NIDDM
      syndrome with reduced pancreatic insulin stores, which is similar to human NIDDM
      in that it has a significant response to glucose (although abnormal in kinetics)
      and preserved sensitivity to tolbutamide, may provide a particularly advantageous
      tool for pharmacological investigations of new insulinotropic agents.

PMID- 9519718
TI  - Severe leptin resistance in brown fat-deficient uncoupling protein promoter
      driven diphtheria toxin A mice despite suppression of hypothalamic neuropeptide Y
      and circulating corticosterone concentrations.
AB  - Brown adipose tissue (BAT) has the capacity for uncoupled mitochondrial
      respiration and is proposed to be a key site for regulating energy expenditure in
      rodents. To better define the role of BAT in energy homeostasis, we previously
      created a line of transgenic mice with deficiency of BAT (UCP promoter-driven
      diphtheria toxin A transgenic mice [UCP-DTA]) mice. These mice develop obesity
      that initially is due to decreased energy expenditure and later accompanied by
      hyperphagia despite increased levels of circulating leptin. In addition, the
      obesity of these mice is accompanied by severe insulin-resistant diabetes and
      hyperlipidemia. To better define the basis for leptin resistance in this model,
      we treated UCP-DTA mice with leptin (300 microg i.p., b.i.d.) and compared their
      response with that of leptin-treated ob/ob and FVB control mice (30 microg i.p.,
      b.i.d.). Leptin treatment of FVB and ob/ob mice decreased their body weight and
      food intake and improved their glucose homeostasis. In contrast, tenfold higher
      dosages of leptin had no effect on body weight, food intake, or circulating
      insulin or glucose concentrations of UCP-DTA mice. Hypothalamic neuropeptide Y
      (NPY) mRNA expression was lower in UCP-DTA mice than in littermate control FVB
      mice in the fed state, and increased progressively in response to food
      restriction as leptin levels fell. In parallel to the levels of hypothalamic NPY,
      corticosterone levels were initially suppressed and rose with food restriction.
      Thus food intake, body weight, and insulin and glucose homeostasis of UCP-DTA
      mice are all extraordinarily resistant to leptin, whereas hypothalamic NPY and
      the hypothalamopituitary adrenal (HPA) axis may remain under leptin control.
      Further elucidation of the mechanisms underlying leptin resistance in UCP-DTA
      mice may provide valuable insights into the basis for leptin resistance in human
      obesity.

PMID- 9519719
TI  - Increased plasma leptin levels are associated with fat accumulation in Japanese
      Americans.
AB  - Although the hormone leptin seems to play a role in ensuring the maintenance of
      adequate energy stores and thereby protects against starvation, its role in the
      regulation of body weight and adiposity under normal circumstances is unclear.
      Overweight individuals have markedly elevated circulating leptin levels,
      suggesting that leptin's effect on food intake and thermogenesis is diminished or
      absent in obesity. Recent evidence, though, indicates that weight gain in Pima
      Indians is associated with relatively decreased levels of the hormone. Because it
      is important to understand whether a deficiency in circulating leptin contributes
      to the development of obesity, we sought to determine whether there is a
      relationship between leptin levels and subsequent changes in adiposity in a more
      typical population. We compared baseline plasma leptin concentrations to changes
      over 5 years in body weight, BMI, and computed tomography-determined total fat in
      492 second- and third-generation Japanese Americans. Subjects were of 100%
      Japanese ancestry; male subjects had a mean BMI at baseline of 25.4 kg/m2 and a
      mean age of 54 years; female subjects had a mean BMI of 23.1 kg/m2 and a mean age
      of 53 years. Changes in weight (men: r = 0.17, P < 0.05; women: r = 0.20, P <
      0.05), BMI (men: r = 0.17, P < 0.05; women: r = 0.18, P < 0.05), and total fat
      (men: r = 0.19, P < 0.05; women: r = 0.20, P < 0.01) were positively correlated
      with baseline leptin levels adjusted for baseline adiposity, fasting insulin, and
      age. In Japanese Americans, then, relatively increased leptin levels are
      associated with greater subsequent gains in weight and adiposity. We concluded
      that in this population, fat accumulation is associated not with leptin
      deficiency but possibly with leptin resistance and is preceded by increased
      leptin levels.

PMID- 9519720
TI  - Plasma leptin concentrations do not appear to decrease insulin-mediated glucose
      disposal or glucose-stimulated insulin secretion in women with normal glucose
      tolerance.
AB  - The aim of this study was to test the hypothesis that plasma leptin
      concentrations contributed to the pathophysiology of NIDDM by decreasing both
      insulin-mediated glucose disposal and glucose-stimulated insulin secretion. The
      study was performed in 60 women with normal oral glucose tolerance. Differences
      in insulin-mediated glucose disposal were determined by comparing the steady
      state plasma glucose (SSPG) concentrations attained at the end of a 180-min
      constant infusion of somatostatin, glucose, and insulin, while comparisons of
      glucose-stimulated insulin secretion were based on the incremental increase in
      insulin concentration 30 min after an oral glucose challenge (deltaIns) as
      compared with the fasting value. The results showed that the higher the fasting
      plasma leptin concentration, the greater the degree of insulin resistance (r =
      0.47, P < 0.01). Furthermore, multiple regression analysis indicated that the
      relationship between leptin and SSPG was independent of age and degree of obesity
      as estimated by BMI. However, since the total integrated plasma insulin response
      was highly correlated with both SSPG (r = 0.80, P < 0.001) and leptin (r = 0.55,
      P < 0.01), multiple regression analysis was repeated, adding total insulin
      response to the model. When this was done, the significant relationship between
      leptin and SSPG disappeared, whereas both BMI (P < 0.03) and insulin response (P
      < 0.001) were correlated with SSPG. A significant relationship between leptin and
      deltaIns was seen, but it was a positive one (r = 0.31, P < 0.02), not a negative
      one as would be expected if circulating levels of leptin inhibited glucose
      stimulated insulin secretion. Furthermore, multiple regression analysis could
      only confirm an independent relationship between deltaIns and SSPG, but not
      between deltaIns and leptin. The results of these studies do not support the view
      that circulating leptin has a primary effect on either insulin action or
      secretion in normal female volunteers. It seems more likely that chronic
      hyperinsulinemia in insulin-resistant individuals acts to increase adipose tissue
      leptin synthesis and secretion, leading to higher ambient leptin concentrations.

PMID- 9519721
TI  - Coronary flow reserve is reduced in young men with IDDM.
AB  - Disturbances of coronary circulation have been reported in diabetic patients with
      microvascular complications but without obstructive coronary atherosclerosis. The
      aim of the present study was to investigate coronary flow reserve in young adult
      patients with IDDM but without microalbuminuria and diabetic autonomic
      neuropathy. Coronary flow reserve was determined in 12 nonsmoking male patients
      with IDDM (age 30.0 +/- 6.6 years) and 12 healthy matched volunteers. Groups were
      similar with respect to blood pressure and serum lipid concentrations, and no
      subject had a positive family history of coronary heart disease. The patients
      with IDDM had normal exercise echocardiography and autonomic nervous function
      tests. Five patients had minimal background retinopathy, and none had
      microalbuminuria. Positron emission tomography and [15O]H2O were used to measure
      myocardial blood flow at rest and after dipyridamole administration. The studies
      were performed during euglycemic hyperinsulinemia (serum insulin approximately 70
      mU/l). The baseline myocardial blood flow was similar in patients with IDDM and
      in control subjects (0.84 +/- 0.18 vs. 0.88 +/- 0.25 ml x g(-1) x min(-1), NS).
      The myocardial blood flow during hyperemia was 29% lower in patients with IDDM
      (3.17 +/- 1.57) compared with the control subjects (4.45 +/- 1.37 ml x g(-1) x
      min(-1), P < 0.05). Consequently, coronary flow reserve (the ratio of flow during
      hyperemia and at rest) was lower in diabetic patients than in control subjects
      (3.76 +/- 1.69 vs. 5.31 +/- 1.86, P < 0.05) and the total coronary resistance
      during hyperemia was higher in diabetic patients (53.7 +/- 31.5) compared with
      the control subjects (31.4 +/- 11.6 mmHg x min x g x ml(-1), P < 0.05). The
      coronary flow reserve was similar in diabetic patients with and without mild
      background retinopathy. No association was found between the coronary flow
      reserve and serum lipid or HbA1c values in either group. Coronary flow reserve is
      impaired in young adult males with IDDM and no or minimal microvascular
      complications and without any evidence of coronary heart disease. This
      abnormality cannot be explained by standard coronary heart disease risk factors.
      The results imply early impairment of coronary vascular reactivity in IDDM
      patients, which may represent an early precursor of future coronary heart disease
      or may contribute to the pathogenesis of diabetic cardiomyopathy.

PMID- 9519722
TI  - Beta-hydroxybutyrate increases reactive oxygen species in late but not in early
      postimplantation embryonic cells in vitro.
AB  - Embryonic dysmorphogenesis has been blocked by antioxidant treatment in vivo and
      in vitro, suggesting that embryonic excess of reactive oxygen species (ROS) has a
      role in the teratogenic process of diabetic pregnancy. We report that the basal
      levels of ROS in dispersed rat embryonic cells in vitro, as determined by
      fluorescence of dichlorofluorescein (DCF), were not different in cells from
      control and diabetic pregnancy at day 10 or 12. Beta-hydroxybutyrate (beta-HB)
      and succinic acid monomethyl ester both augmented DCF fluorescence in cells from
      day 12 embryos of normal and diabetic rats but not from day 10 embryos. Cells of
      day 10 and day 12 embryos from normal and diabetic rats responded to increasing
      glucose concentrations with a dosage-dependent alleviation of DCF fluorescence.
      Day 10 embryonic cells exhibited high glucose utilization rates and high pentose
      phosphate shunt rates, but low mitochondrial oxidation rates. Moreover, in vitro
      culture of embryos between gestational days 9 and 10 in the presence of 20%
      oxygen induced an increased and glucose-sensitive oxidation of glucose compared
      with embryos not cultured in vitro. At gestation day 12, however, pentose
      phosphate shunt rates showed a decrease, whereas the mitochondrial beta-HB
      oxidation rates were increased compared with those at gestation day 10. This was
      paralleled by a lower expression of glucose 6-phosphate dehydrogenase- and
      phosphofructokinase-mRNA levels at day 12 than at day 10. On the other hand, H
      ferritin mRNA expression at day 12 was high compared with day 10. None of the
      mRNA species investigated were affected by the diabetic state of the mother. It
      was concluded that beta-HB-induced stimulation of mitochondrial oxidative events
      may lead to the generation of ROS at gestational day 12, but probably not at day
      10, when only a minute amount of mitochondrial activity occurs. Thus our results
      do not support the notion of diabetes-induced mitochondrial oxidative stress
      before the development of a placental supply of oxygen.

PMID- 9519723
TI  - Genetic structure of IDDM1: two separate regions in the major histocompatibility
      complex contribute to susceptibility or protection. Belgian Diabetes Registry.
AB  - We analyzed 11 markers in the IDDM1 region in 120 IDDM patients and 83 healthy
      control subjects who were fully matched for the highest risk HLA-DQA1*0301-DQB1
      *0302/DQA1*0501-DQB1*0201 genotype. Our study provides strong evidence that two
      regions in the major histocompatibility complex contribute to IDDM susceptibility
      or protection. First, despite selection for highest IDDM-associated risk DQ
      genotypes, this region displays extensive linkage disequilibrium (LD) differences
      between IDDM patients and control subjects. A second critical region was mapped
      around the microsatellite locus D6S273 centromeric of TNF, and it is
      approximately 200 kb in size. LD analysis shows that "diabetogenic haplotypes"
      may have resulted from a recombination telomeric of D6S1014 in the region of
      D6S273 and TNFa. Haplotype analysis using HLA and microsatellite loci refines
      IDDM risk assessment in carriers of the HLA-DQ highest risk genotype.

PMID- 9519724
TI  - Hyperinsulinemia is associated with the incidence of hypertension and
      dyslipidemia in middle-aged men.
AB  - Insulin resistance or compensatory hyperinsulinemia has been associated with
      hypertension and dyslipidemia in cross-sectional studies. In contrast, evidence
      from prospective population-based studies, which could establish the time order
      of the relationship, is sparse and inconsistent. Therefore, we investigated the
      associations of hyperinsulinemia with the incidence of hypertension and
      dyslipidemia in the Kuopio Ischemic Heart Disease Risk Factor Study, a population
      based 4-year follow-up study of middle-aged men from eastern Finland. Out of 975
      men who had no diabetes, 543 had resting systolic blood pressure (sBP) of < 165
      mmHg and resting diastolic blood pressure (dBP) of < 95 mmHg at baseline and were
      not taking antihypertensive medication, and 764 had serum triglycerides of < 2.3
      mmol/l and HDL cholesterol of > or =1.0 mmol/l at baseline. In logistic
      regression models adjusted for age, baseline resting blood pressure, baseline
      lipids, obesity, weight change, and other risk factors, men with hyperinsulinemia
      (fasting insulin in the highest quintile, > or =12.0 mU/l) at baseline had a 2.0
      fold (95% CI 1.1-3.5, P = 0.025) incidence of hypertension (sBP of > or =165 or
      dBP of > or =95 mmHg), a 2.1-fold (95% CI 1.3-3.4, P = 0.002) incidence of
      dyslipidemia (serum HDL cholesterol of < 1.0 mmol/l or serum triglycerides of >
      or =2.3 mmol/l), and a 2.6-fold (95% CI 1.1-6.3, P = 0.028) incidence of the
      combination of these disorders in 4 years, compared with normoinsulinemic men.
      These findings demonstrate the role of hyperinsulinemia in incident hypertension
      and dyslipidemia and suggest that both hypertension and dyslipidemia are
      associated with insulin metabolism disturbance, independently of obesity and body
      weight.

PMID- 9519725
TI  - New mitochondrial DNA homoplasmic mutations associated with Japanese patients
      with type 2 diabetes.

PMID- 9519726
TI  - Association of apolipoprotein epsilon2 allele with diabetic nephropathy in
      Caucasian subjects with IDDM.

PMID- 9519727
TI  - Linkage and association between a CD4 gene polymorphism and IDDM in Danish IDDM
      patients. The Danish IDDM Epidemiology and Genetics Group, and The Danish Study
      Group of Diabetes in Childhood.

PMID- 9519728
TI  - Human hormone-sensitive lipase: genetic mapping, identification of a new
      dinucleotide repeat, and association with obesity and NIDDM.

PMID- 9519729
TI  - Prohormone convertase 1 in obesity, gestational diabetes mellitus, and NIDDM: no
      evidence for a major susceptibility role.

PMID- 9519730
TI  - Induction of hyperinsulinemia combined with hyperglycemia and
      hypertriglyceridemia increases plasminogen activator inhibitor 1 in blood in
      normal human subjects.
AB  - Hypofibrinolysis caused by increased plasminogen activator inhibitor 1 (PAI-1)
      has been implicated in the vasculopathy of type 2 diabetes, typified by increased
      insulin, glucose, and triglycerides. However, short-term infusions of insulin
      have not increased PAI-1 in normal subjects. We hypothesized that induction of
      increased insulin accompanied by increased glucose and triglycerides would
      increase PAI-1. Accordingly, 30% glucose and 10% Intralipid were infused for 6 h
      in ten normal lean individuals (54 +/- 3 years) resulting in increased insulin
      (42 +/- 5 microU/dl), glucose (200 +/- 24 mg/dl), and triglycerides (425 +/- 45
      mg/dl), simulating changes in type 2 diabetes. In contrast to results with
      infusion of saline alone (n = 16) and euglycemic-hyperinsulinemic clamps (n = 10,
      serum insulin = 89 +/- 7 microU/dl), PAI-1 in blood increased significantly 6 h
      after the onset of infusion (15 +/- 5 ng/ml, P < 0.05 vs. baseline = 7.4 +/- 1.1,
      saline 6 h = 3.4 +/- 1.1, and insulin alone 6 h = 3.7 +/- 0.8) and remained
      elevated for an additional 6 h (combined infusion = 13.8 +/- 3.8 ng/ml, saline =
      6.7 +/- 2 ng/ml, insulin alone = 7.8 +/- 1.7 ng/ml, P = 0.06). Our data suggest
      that combined hyperinsulinemia, hypertriglyceridemia, and hyperglycemia are
      likely to contribute to hypofibrinolysis of type 2 diabetes by increasing the
      blood levels of PAI-1. Moreover, these results underscore the potential
      importance of modifying insulin resistance as well as achieving glycemic and
      lipidemic control in individuals with type 2 diabetes.

PMID- 9519731
TI  - Hypothalamic pro-opiomelanocortin mRNA is reduced by fasting and [corrected] in
      ob/ob and db/db mice, but is stimulated by leptin.
AB  - Reduction in the activity of the alpha-melanocyte-stimulating hormone (alpha-MSH)
      system causes obesity, and infusions of alpha-MSH can produce satiety, raising
      the possibility that alpha-MSH may mediate physiological satiety signals. Since
      alpha-MSH is coded for by the pro-opiomelanocortin (POMC) gene, we examined if
      POMC gene expression would be inhibited by fasting in normal mice or in models of
      obesity characterized by leptin insufficiency (ob/ob) or leptin insensitivity
      (db/db). In wild-type mice, hypothalamic POMC mRNA was decreased > 60% after a 2
      day fast and was positively correlated with leptin mRNA. Similarly, compared with
      controls, POMC mRNA was decreased by at least 60% in both db/db and ob/ob mice.
      POMC mRNA was negatively correlated with both neuropeptide Y (NPY) and melanin
      concentrating hormone (MCH) mRNA. Finally, treatment of both male and female
      ob/ob mice with leptin stimulated hypothalamic POMC mRNA by about threefold.
      These results suggest that impairment in production, processing, or
      responsiveness to alpha-MSH may be a common feature of obesity and that
      hypothalamic POMC neurons, stimulated by leptin, may constitute a link between
      leptin and the melanocortin system.

PMID- 9519732
TI  - Elevated free fatty acids induce uncoupling protein 3 expression in muscle: a
      potential explanation for the effect of fasting.
AB  - The newly described uncoupling protein 3 (UCP3) may make an important
      contribution to thermogenesis in humans because of its high level of expression
      in skeletal muscle. Contrary to expectations, fasting, a condition that reduces
      resting energy expenditure, has been reported to increase UCP3 expression in
      muscle. We have confirmed that a 10-fold increase in UCP3 mRNA levels occurs in
      rat quadriceps muscle between 12 and 24 h of food removal. A less consistent
      twofold increase in muscle UCP2 mRNA levels was observed in animals fasted for up
      to 72 h. Administration of recombinant leptin to prevent a fall in circulating
      leptin levels did not eliminate the fasting-induced increase in quadriceps UCP3
      expression. Administration of a high dose of glucocorticoid to fed animals to
      mimic the increase in corticosterone induced by fasting did not reproduce the
      increase in UCP3 expression observed in fasted animals. In contrast, elevation of
      circulating free fatty acid levels in fed animals by Intralipid plus heparin
      infusion caused significant increases in the UCP3/actin mRNA ratio compared with
      saline-infused fed controls in both extensor digitorum longus (2.01 +/- 0.34 vs.
      0.68 +/- 0.11, P = 0.002) and soleus muscles (0.31 +/- 0.07 vs. 0.09 +/- 0.02, P
      = 0.014). We conclude that free fatty acids are a potential mediator of the
      increase in muscle UCP3 expression that occurs during fasting. This seemingly
      paradoxical induction of UCP3 may be linked to the use of free fatty acid as a
      fuel rather than an increased need of the organism to dissipate energy.

PMID- 9519733
TI  - Pancreatic beta-cell glucokinase: closing the gap between theoretical concepts
      and experimental realities.
AB  - There remains a wide gap between theoretical concepts and experimental realities
      in the enzyme kinetics and biochemical genetics of the pancreatic beta-cell
      glucokinase-glucose sensor. It is the goal of present efforts in many
      laboratories to bridge this gap. This perspective intends to provide a timely
      review of this crucial aspect of research in glucose homeostasis. It deals
      briefly with some fundamentals of glucokinase enzyme kinetics, offers some
      pertinent biochemical genetic considerations, takes stock of the current
      experimental database of the field by emphasizing human studies and referring to
      recent mouse studies, and ventures a few extrapolations into the future of this
      endeavor.

PMID- 9519735
TI  - Successful islet autotransplantation in humans: functional insulin secretory
      reserve as an estimate of surviving islet cell mass.
AB  - Islet autotransplantation for treatment of chronic painful pancreatitis in
      nondiabetic patients reliably establishes normoglycemia and phasic insulin
      secretion and can achieve prolonged insulin independence. Whether functional
      transplanted beta-cell reserve is normal after intrahepatic islet transplantation
      is not known, nor is it known whether conventional measures of insulin secretion
      accurately reflect the functional beta-cell mass. To determine insulin secretory
      reserve after islet transplant, we performed studies of glucose potentiation of
      arginine-induced insulin secretion (GPAIS) in eight recipients of intrahepatic
      islet autotransplants. All eight subjects (and matched, healthy controls) were
      studied cross-sectionally 49 +/- 12 months posttransplant, and four subjects were
      studied pre- and posttransplant. Subjects had received a mean +/- SE of 479,000
      +/- 79,000 islets, and all were insulin independent and normoglycemic at the time
      of study. Acute insulin responses to arginine, glucose, and GPAIS were
      significantly reduced after islet transplantation in both study groups.
      Importantly, the magnitudes of these three responses were highly correlated to
      the mass of islets transplanted (response to glucose: r = 0.84, P < 0.01;
      response to arginine: r = 0.69, P < 0.05; response to GPAIS = 0.81, P < 0.01).
      Data from hemipancreatectomized and normal control subjects generally agreed with
      the regression lines. These findings demonstrate that despite normoglycemia and
      insulin independence, recipients of intrahepatic islet transplantation have
      significantly reduced functional beta-secretory reserve and that after islet
      transplantation, functional beta-cell mass can be estimated by measurements of
      glucose and arginine-induced insulin responses. Thus, these measurements can be
      used to estimate the mass and functional capacity of islets surviving
      intrahepatic transplantation in humans.

PMID- 9519734
TI  - Transplantation of allogeneic islets of Langerhans in the rat liver: effects of
      macrophage depletion on graft survival and microenvironment activation.
AB  - Early impairment of islet function and graft loss limit the success of allogeneic
      islet transplantation. Nonspecific inflammatory events occurring at the
      transplant site immediately after grafting, involving the production of cytokines
      and free radicals and sinusoidal endothelial cell (SEC) activation, may
      contribute to islet cell damage. To evaluate whether Kupffer cell inactivation
      would result in prolonged allograft survival in a model system of intrahepatic
      islet transplantation in rats, we systemically administered either gadolinium
      chloride (GdCl3) or dichloromethylene diphosphonate (Cl2MDP) to assess the
      effects of macrophage inactivation on rejection and on the release of
      proinflammatory molecules, as well as to assess the functional profile of SEC.
      The results obtained were compared with those observed in untreated, sham
      injected animals and in rats receiving intraportal infusions of microbeads.
      Transient macrophage inhibition, particularly in hepatic Kupffer cells, is
      associated with significant prolongation of graft survival after intraportal
      islet allotransplantation (ITx) in rats: 7.2 days in the control group versus
      11.9 days in the GdCl3 group (P < 0.01) and 15.6 days in the Cl2MDP group (P <
      0.0006), respectively. Although systemic release of inflammatory mediators was
      observed only when islet transplantations were performed and it could be
      inhibited by macrophage-targeting treatments, perturbation of the functional
      profile of endothelial cells was also observed when microembolization was induced
      by the use of microbeads and could not be prevented by macrophage inhibition.
      These experiments provide evidence to support the concept that macrophages play a
      key role in early inflammatory events known to adversely affect islet engraftment
      and suggest that manipulation of nonspecific immune activation by inhibition of
      macrophage function may facilitate hepatic engraftment of islet allografts. The
      mechanisms mediating this effect are likely to include prevention of release of
      tumor necrosis factor-alpha, interleukin-1beta, and NO and interference with the
      rate of immune response to the islets.

PMID- 9519736
TI  - Independent genetic regulation of T-cell and antigen-presenting cell
      participation in autoimmune islet inflammation.
AB  - Genetic susceptibility to type 1 diabetes in the nonobese diabetic (NOD) mouse
      involves at least 17 Idd loci. Idd1 has been mapped to a class II gene in the
      major histocompatibility complex (MHC), whereas the products and functions of the
      remaining Idd loci are unresolved. To investigate how non-MHC Idd genes regulate
      islet inflammation and IDDM progression, NOD mice were compared with the nonobese
      diabetes-resistant (NOR) mouse, a related MHC-identical strain that possesses a
      subset of the NOD-derived alleles at the Idd loci. Using quantitative reverse
      transcriptase-polymerase chain reaction amplification and immunohistochemistry,
      we observed that disease resistance in NOR mice is reflected by a protracted
      block at the earliest stage of insulitis. In NOD islets, early antigen-presenting
      cell (APC) recruitment to islet lesions was temporally coincident with
      progressive T-cell infiltration. In striking contrast, islet infiltrates in NOR
      mice were composed of APCs with minimal contribution from T-cells and T-cell
      derived inflammatory cytokines, conferring apparent resistance to invasive
      insulitis and beta-cell destruction. This is the first evidence that a subset of
      Idd susceptibility loci independently regulate T-cell and APC participation in
      insulitis progression. As progress is made toward identification of the Idd gene
      products, it will be crucial to determine how they regulate diabetogenesis. Our
      data define distinct cellular stages of IDDM pathogenesis in which the impact of
      Idd genes can be readily analyzed.

PMID- 9519737
TI  - Alpha-ketoisocaproate is not a true substrate for ATP production by pancreatic
      beta-cell mitochondria.
AB  - The ability of alpha-ketoisocaproate (KIC) to induce ATP production in isolated
      mitochondria from pancreatic beta-cells was examined with a bioluminometric
      method. There was no ATP production from KIC when tested alone or in combination
      with malate (1 mmol/l), nor did DL-beta-hydroxybutyrate induce mitochondrial ATP
      production, whereas palmitoyl-carnitine and pyruvate were efficient stimulators
      of mitochondrial ATP production in the presence of an equimolar concentration of
      malate. However, KIC stimulated the mitochondrial ATP production when tested in
      combination with glutamate (10 mmol/l). The concentration necessary to obtain
      half-maximal stimulation was approximately 50 micromol/l KIC, and maximal
      activity, comparable to that obtained with fatty acids, was reached at 1 mmol/l
      KIC. Higher KIC concentrations inhibited the mitochondrial ATP production,
      whereas a plateau was attained at 1 mmol/l KIC in the presence of glutamine. Ca2+
      stimulated the maximal mitochondrial ATP production induced by KIC. Maximal
      stimulation was obtained with 300 nmol/l Ca2+ in the presence of 0.3 mmol/l KIC.
      Ca2+ reduced the concentration of KIC necessary for half-maximal stimulation to
      <30 micromol/l. Leucine stimulated the mitochondrial ATP production in the
      presence of glutamate to the same extent as KIC. Half-maximal stimulation was
      observed with 2 mmol/l leucine. There were no additive effects on mitochondrial
      ATP production when KIC and leucine were tested in combination. The results
      demonstrate that KIC by itself is not a mitochondrial substrate for ATP
      production. KIC must transaminate with glutamate or glutamine to yield alpha
      ketoglutarate and leucine. Since leucine allosterically activates glutamate
      dehydrogenase, which also produces alpha-ketoglutarate, the insulinogenic effect
      of KIC may in part be due to the intramitochondrial generation of alpha
      ketoglutarate. Since KIC-induced ATP production reaches a plateau already at
      micromolar concentrations (i.e., far below the concentrations at which KIC
      induces insulin release), it is proposed here that the catabolism of KIC may
      induce additional signals related to insulin release.

PMID- 9519738
TI  - Stimulation of insulin release by repaglinide and glibenclamide involves both
      common and distinct processes.
AB  - The action of repaglinide, a novel insulin secretagogue, was compared with the
      sulfonylurea glibenclamide with regard to the hypoglycemic action in vivo,
      binding to betaTC-3 cells, insulin secretion from perifused mouse islets, and
      capacity to stimulate exocytosis by direct interaction with the secretory
      machinery in single voltage-clamped mouse beta-cells. Two binding sites were
      identified: a high-affinity repaglinide (KD = 3.6 nmol/l) site having lower
      affinity for glibenclamide (14.4 nmol/l) and one high-affinity glibenclamide (25
      nmol/l) site having lower affinity for repaglinide (550 nmol/l). In contrast to
      glibenclamide, repaglinide (in concentrations as high as 5 micromol/l) lacked the
      ability to enhance exocytosis in voltage-clamped beta-cells. Repaglinide was more
      potent than glibenclamide in stimulating insulin release from perifused mouse
      islets (EC50 29 vs. 80 nmol/l). The greater potency of repaglinide in vitro was
      paralleled by similar actions in vivo. The ED50 values for the hypoglycemic
      action were determined to be 10.4 and 15.6 microg/kg after intravenous and oral
      administration, respectively. The corresponding values for glibenclamide were
      70.3 microg/kg (intravenous) and 203.2 microg/kg (oral). Further, repaglinide (1
      mg/kg p.o.) was effective (P < 0.001) as an insulin-releasing agent in a rat
      model (low-dose streptozotocin) of type 2 diabetes. These observations suggest
      that the insulinotropic actions of repaglinide and glibenclamide in vitro and in
      vivo are secondary to their binding to the high-affinity repaglinide site and
      that the insulinotropic action of repaglinide involves both distinct and common
      cellular mechanisms.

PMID- 9519739
TI  - Palmitate and myristate selectively mimic the effect of glucose in augmenting
      insulin release in the absence of extracellular Ca2+.
AB  - Under Ca2+-free conditions, activation of the pancreatic beta-cell with forskolin
      and 12-O-tetradecanoylphorbol 13-acetate (TPA) is permissive for the augmentation
      of insulin release by glucose and other nutrients. The ability of fatty acids to
      mimic the effect of glucose and thereby augment insulin secretion in the absence
      of extracellular Ca2+ is the focus of the present study. In the absence of
      extracellular Ca2+, glucose, palmitate, and myristate had no effect on insulin
      release. When, under Ca2+-free conditions, the islets were treated with forskolin
      to raise cyclic AMP levels and activate protein kinase A and with TPA to activate
      protein kinase C, glucose, palmitate, and myristate all augmented release to
      approximately the same extent. No other saturated fatty acid with chain lengths
      in the C = 6-22 range augmented the release of insulin. This selective
      augmentation by palmitate or myristate was not seen with forskolin alone, and was
      seen slightly with TPA and strongly with the combination of forskolin and TPA.
      The response, which developed slowly and had a time course similar to that of
      second-phase insulin release, was abolished by the physiological inhibitor
      norepinephrine. The results suggest that the mechanism underlying the Ca2+
      independent augmentation of insulin release by glucose and other nutrients
      involves the proposed malonyl-CoA/long-chain acyl-CoA pathway with specificity
      for myristoyl- and palmitoyl-CoA esters and/or their derivatives.

PMID- 9519740
TI  - Role of apoptosis in failure of beta-cell mass compensation for insulin
      resistance and beta-cell defects in the male Zucker diabetic fatty rat.
AB  - To define the mechanisms involved in the evolution of diabetes in the Zucker
      diabetic fatty (ZDF) rat, beta-cell mass and replication rates were determined by
      immunochemistry, point-counting morphometry, and 6-h 5-bromo-2'-deoxyuridine
      (BrdU) incorporation. The beta-cell mass in 5- to 7-week-old prediabetic ZDF rats
      (4.3 +/- 0.06 mg) was similar to age-matched insulin-resistant Zucker fatty (ZF)
      rats (3.7 +/- 0.05 mg) and greater than that in Zucker lean control (ZLC) rats
      (1.9 +/- 0.3, P < 0.05). At 12 weeks (after diabetes onset), beta-cell mass in
      the ZDF rats (8.1 +/- 1.7 mg) was significantly lower than the ZF rats (15.7 +/-
      1.8 mg). The mass in the ZF rats was significantly greater than in the ZLC rats
      (4.3 +/- 0.8 mg, P < 0.05). The beta-cell proliferation rate (mean of both time
      points) was significantly greater in the ZDF rats (0.88 +/- 0.1%) compared with
      the ZF and ZLC rats (0.53 +/- 0.07%, 0.62 +/- 0.07%, respectively, P < 0.05), yet
      ZDF rats have a lower beta-cell mass than the ZF rats despite a higher
      proliferative rate. Morphological evidence of neogenesis and apoptosis is evident
      in the ZF and ZDF rats. In addition, even at 5-7 weeks a modest defect in insulin
      secretion per beta-cell unit was found by pancreas perfusion. These studies
      provide evidence that the expansion of beta-cell mass in response to insulin
      resistance and insulin secretory defects in diabetic ZDF rats is inadequate. This
      failure of beta-cell mass expansion in the ZDF rat does not appear to be from a
      reduction in the rate of beta-cell proliferation or neogenesis, suggesting an
      increased rate of cell death by apoptosis.

PMID- 9519741
TI  - Tolbutamide and diazoxide influence insulin secretion by changing the
      concentration but not the action of cytoplasmic Ca2+ in beta-cells.
AB  - Sulfonylureas stimulate insulin secretion by blocking ATP-sensitive K+ channels
      (K+-ATP channels) of the beta-cell membrane, thereby causing depolarization, Ca2+
      influx, and rise in cytoplasmic Ca2+ concentration ([Ca2+]i), whereas diazoxide
      inhibits insulin secretion by opening K+-ATP channels. It has been suggested
      recently that these drugs also respectively increase and decrease the efficacy of
      Ca2+ on exocytosis. This hypothesis was tested here with intact islets or single
      beta-cells from normal mice. Depolarizing islet cells by raising extracellular K+
      from 4.8 to 15, 30, and 60 mmol/l progressively raised [Ca2+]i and stimulated
      insulin secretion. The magnitude of the [Ca2+]i rise produced by a subsequent
      addition of 100 micromol/l tolbutamide decreased as the concentration of K+ was
      increased. The effect on insulin secretion paralleled that on [Ca2+]i. Similarly,
      the magnitudes of the [Ca2+]i drop and of the inhibition of insulin secretion
      produced by 250 micromol/l diazoxide were inversely related to the concentration
      of K+. Either drug was effective on secretion only when it increased or decreased
      [Ca2+]i. Exocytosis of insulin granules from single, voltage-clamped beta-cells
      was also studied by measuring cell capacitance changes. In the perforated patch
      configuration, exocytosis was evoked by depolarizing pulses. Addition of
      tolbutamide to the extracellular medium did not affect the Ca2+ current and the
      resulting change in cell capacitance. In the whole-cell configuration, cell
      capacitance increased with the concentration of free Ca2+ in the solution
      diffusing from the pipette into the cell. It was markedly potentiated by cAMP,
      was inhibited by activation of alpha2-adrenoceptors with clonidine, and was
      strongly augmented by acetylcholine. In contrast, tolbutamide was ineffective
      whether applied intra- or extracellularly, at low or high free Ca2+, and with or
      without cAMP. Diazoxide also failed to interfere directly with exocytosis. These
      results indicate that tolbutamide and diazoxide affect insulin secretion by
      changing the concentration, not the action, of Ca2+ in beta-cells.

PMID- 9519742
TI  - Effects of depletion of mitochondrial DNA in metabolism secretion coupling in INS
      1 cells.
AB  - Mitochondrial dysfunction due to alterations in the mitochondrial genome (mtDNA)
      has recently attracted much attention, with the finding that mutations in the
      mitochondrially encoded proteins perturb cell function. Several disorders have
      been linked to such genetic changes, including a specific diabetic phenotype.
      Using ethidium bromide (EtBr) that intercalates into mtDNA, we have effectively
      eliminated functions under the control of mtDNA from the highly differentiated
      INS-1 insulin-secreting cell line. We have investigated the consequences on
      insulin secretion, mitochondrial enzyme activity, organelle structure, and
      membrane polarization in such cells (INS-1 rho0). Under these conditions, the
      mitochondrial membrane potential fails to hyperpolarize in response to either
      glucose or methylsuccinate. In agreement with this finding, the morphology of the
      mitochondria is altered in the presence of EtBr, sharing similarities with
      mitochondria in which the membrane potential has been collapsed with the
      protonophore carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP). In
      addition, there is no effect of either nutrient secretagogue at the level of the
      plasma membrane potential, although the effect of the depolarizing agent KCl on
      membrane depolarization is completely preserved. Similarly, glucose and
      methylsuccinate fail to increase insulin secretion, whereas KCl is still
      effective. To test further the effects of mtDNA depletion on exocytosis, we
      permeabilized INS-1 cells with Staphylococcus aureus alpha-toxin, which forms
      small holes in the plasma membrane. In contrast to control cells, mitochondrial
      substrates were incapable of stimulating insulin secretion in mtDNA-deficient
      cells, emphasizing that the defect in secretion lies at the level of
      mitochondrial function rather than in the exocytotic process. The results
      indicate the paramount importance of the mitochondria in the downstream effects
      elicited by exposure to elevated concentrations of nutrient secretagogue.

PMID- 9519743
TI  - 13C/31P NMR studies on the mechanism of insulin resistance in obesity.
AB  - The mechanism of insulin resistance in obesity was examined in ten obese (BMI 33
      +/- 1 kg/m2) and nine lean (BMI 22 +/- 1 kg/m2) Caucasian women during a
      hyperglycemic-hyperinsulinemic clamp using 13C and 31P nuclear magnetic resonance
      (NMR) spectroscopy to measure rates of muscle glycogen synthesis and
      intramuscular glucose-6-phosphate (G-6-P) concentrations. Under similar steady
      state plasma concentrations of glucose (approximately 11 mmol/l) and insulin
      (approximately 340 pmol/l), rates of muscle glycogen synthesis were reduced
      approximately 70% in the obese subjects (52 +/- 8 micromol/[l muscle-min]) as
      compared with the rates in the lean subjects (176 +/- 22 micromol/[l muscle-min];
      P < 0.0001). Basal concentrations of intramuscular G-6-P were similar in the
      obese and lean subjects; but during the clamp, G-6-P failed to increase in the
      obese group (deltaG-6-P obese 0.044 +/- 0.011 vs. lean 0.117 +/- 0.011 mmol/l
      muscle; P < 0.001), reflecting decreased muscle glucose transport and/or
      phosphorylation activity. We conclude that insulin resistance in obesity can be
      mostly attributed to impairment of insulin-stimulated muscle glycogen synthesis
      due to a defect in glucose transport and/or phosphorylation activity.

PMID- 9519744
TI  - Insulin-induced hexokinase II expression is reduced in obesity and NIDDM.
AB  - NIDDM and obesity are characterized by decreased insulin-stimulated glucose
      uptake in muscle. It has been suggested that impaired glucose phosphorylation to
      glucose-6-phosphate, catalyzed in muscle by hexokinase (HK)II, may contribute to
      this insulin resistance. Insulin is known to increase HKII mRNA, protein, and
      activity in lean nondiabetic individuals. The purpose of this study was to
      determine whether defects in insulin-stimulated HKII expression and activity
      could contribute to the insulin resistance of obesity and NIDDM. Fifteen lean
      nondiabetic control subjects, 17 obese nondiabetic subjects, and 14 obese NIDDM
      patients were studied. Percutaneous muscle biopsies of the vastus lateralis were
      performed in conjunction with leg balance and local indirect calorimetry
      measurements before and at the end of a 3-h euglycemic-hyperinsulinemic clamp (40
      or 240 mU x min(-1) x m[-2]). Leg glucose uptake in response to the 40-mU insulin
      infusion was higher in the lean control subjects (2.53 +/- 0.35 micromol x min(
      1) per x 100 ml leg vol) than in obese (1.46 +/- 0.50) or NIDDM (0.53 +/- 0.25, P
      < 0.05) patients. In response to 240 mU insulin, leg glucose uptake was similar
      in all of the groups. In response to 40 mU insulin, HKII mRNA in lean control
      subjects was increased 1.48 +/- 0.18-fold (P < 0.05) but failed to increase
      significantly in the obese (1.12 +/- 0.24) or NIDDM (1.14 +/- 0.18) groups. In
      response to 240 mU insulin, HKII mRNA was increased in all groups (control
      subjects 1.48 +/- 0.18, P < 0.05 vs. basal, obese 1.30 +/- 0.16, P < 0.05, and
      NIDDM 1.25 +/- 0.14, P < 0.05). Under basal conditions, HKI and HKII activities
      did not differ significantly between groups. Neither the 40 mU nor the 240 mU
      insulin infusion affected HK activity. Total HKII activity was reduced in the
      obese subjects (4.33 +/- 0.08 pmol x min(-1) x g(-1) muscle protein) relative to
      the lean control subjects (5.00 +/- 0.08, P < 0.05). There was a further
      reduction in the diabetic patients (3.10 +/- 0.10, P < 0.01 vs. the control
      subjects, P < 0.01 vs. the obese subjects). Resistance to insulin's metabolic
      effects extends to its ability to induce HKII expression in obesity and NIDDM.

PMID- 9519745
TI  - Troglitazone prevents hyperglycemia-induced but not glucosamine-induced insulin
      resistance.
AB  - Hyperglycemia can lead directly to a secondary state of insulin resistance or can
      worsen a preexisting insulin-resistant state. Troglitazone is an orally active
      hypoglycemic agent that has been shown to ameliorate insulin resistance and
      hyperinsulinemia in both diabetic animal models and NIDDM subjects. To determine
      whether this drug could prevent the development of hyperglycemia-induced insulin
      resistance and to investigate the mechanism by which this might occur, we studied
      troglitazone's effect on insulin action in rats made hyperglycemic or infused
      with glucosamine. Normal male SD rats were fed regular powdered diet with or
      without troglitazone as a food admixture (0.2%). After 2 weeks, rats were made
      hyperglycemic with glucose (52 mg x kg(-1) x min[-1]) and somatostatin (0.8
      microg x kg(-1) x min[-1]) infusion or were infused with glucosamine (6.5 mg x
      kg(-1) x min[-1]) for 6.5 h. In vivo insulin action was measured by the
      hyperinsulinemic-euglycemic clamp technique at a submaximal (24 pmol x kg(-1) x
      min[-1]) or maximal (240 pmol x kg(-1) x min[-1]) insulin infusion rate. The
      infusion of glucose and somatostatin caused a pronounced rise in the plasma
      glucose concentration (19.8 +/- 0.6 mmol/l) compared with saline-infused animals
      (8.0 +/- 0.2 mmol/l; P < 0.001). Hyperglycemia resulted in insulin resistance, as
      evidenced by a marked reduction in the submaximal glucose disposal rate (GDR) (78
      +/- 7 vs. 135 +/- 6 micromol x kg(-1) x min(-1); P < 0.01) and maximal GDR (141
      +/- 9 vs. 237 +/- 6 micromol x kg(-1) x min(-1); P < 0.01) compared with the
      control group. Troglitazone treatment largely prevented the hyperglycemia-induced
      decline in submaximal (116 +/- 7 micromol x kg(-1) x min[-1]) and maximal GDR
      (209 +/- 9 micromol x kg(-1) x min(-1); P < 0.05). Glucosamine infusion also
      resulted in a marked reduction in the submaximal GDR (85 +/- 3 vs. 135 +/- 6
      micromol x kg(-1) x min(-1); P < 0.01) and maximal GDR (137 +/- 14 vs. 237 +/- 6
      micromol x kg(-1) x min(-1); P < 0.01) compared with the control group. In
      contrast to the results in the hyperglycemic animals, troglitazone treatment had
      no effect on glucosamine-induced insulin resistance. In summary, 1) in normal
      rats, experimental hyperglycemia, as well as glucosamine infusion, led to a
      marked state of peripheral and hepatic insulin resistance; 2) troglitazone
      treatment prevented the hyperglycemia-induced, but not the glucosamine-induced,
      insulin resistance; and 3) either troglitazone acts at one or more sites proximal
      to the entry of glucosamine into the hexosamine pathway, or the increased flux of
      glucose-derived products through the hexosamine pathway is not a major mechanism
      for the hyperglycemia-induced defect in insulin action in these animals.

PMID- 9519746
TI  - Upregulation of the vascular endothelial growth factor/vascular endothelial
      growth factor receptor system in experimental background diabetic retinopathy of
      the rat.
AB  - Vascular endothelial growth factor (VEGF) is a major contributor to retinal
      neovascularization. The possible participation of VEGF and its high-affinity
      tyrosine kinase receptors, flk-1 and flt-1, in early background diabetic
      retinopathy was studied in the streptozotocin-induced diabetic rat model of
      experimental retinopathy using in situ hybridization, blotting techniques, and
      immunohistochemistry. Diabetic retinopathy was assessed by quantitative
      morphometry of retinal digest preparations. The number of acellular capillaries
      increased 2.7-fold in diabetic animals with diabetes' duration of 6 months
      compared with nondiabetic controls. VEGF expression was not detectable by in situ
      hybridization in nondiabetic rats but was highly increased in the ganglion cell
      layer and in the inner and outer nuclear layers of retinas from diabetic animals.
      VEGF protein was extractable only from diabetic retinas, and a strong
      immunolabeling was detected in vascular and perivascular structures. Increased
      flk-1 and flt-1 mRNA levels were also found in the ganglion cell and both nuclear
      layers of diabetic samples only. Dot blot and Western blot analyses confirmed the
      increase in flk-1 mRNA and protein in diabetic retinas. Also, flk-1
      immunoreactivity was associated with vascular and nonvascular structures of the
      inner retinas from diabetic animals. These data obtained from a rodent model in
      which retinal neovascularization does not occur support the concept that the
      VEGF/VEGF receptor system is upregulated in early diabetic retinopathy.

PMID- 9519747
TI  - Influence of chronic exposure to high concentrations of D-glucose and long-term
      beta-blocker treatment on intracellular calcium concentrations of porcine aortic
      endothelial cells.
AB  - Clinical observations indicate that diabetes leads to micro- and macroangiopathy
      involving endothelial dysfunction. Because recent studies indicate an
      antiangiopathic effect of celiprolol, but not of metoprolol, in type 1 diabetes,
      we investigated the direct influence of exposure to high D-glucose concentrations
      on endothelial cells and the possible effects of both beta-blockers. Nine
      different chronic treatments were carried out on cultured porcine aortic
      endothelial cells: 1) 5 mmol/l D-glucose ("normoglycemic" cells), 2) 5 mmol/l D
      glucose plus 15 mmol/l L-glucose (osmotic control), 3) 5 mmol/l D-glucose plus
      0.5 micromol/l celiprolol, 4) 5 mmol/l D-glucose plus 0.05 micromol/l metoprolol,
      5) 5 mmol/l D-glucose plus 0.5 micromol/l celiprolol plus 5 micromol/l
      propranolol, 6) 20 mmol/l D-glucose ("hyperglycemic" cells), 7) 20 mmol/l D
      glucose plus 0.5 micromol/l celiprolol, 8) 20 mmol/l D-glucose plus 0.05
      micromol/l metoprolol, and 9) 20 mmol/l D-glucose plus 0.5 micromol/l celiprolol
      plus 5 micromol/l propranolol. Using the Fura-2 technique, application of either
      1 nmol/l bradykinin or 1 micromol/l ATP to the normoglycemic endothelial cells
      led to a significant increase in intracellular calcium, whereas the hyperglycemic
      cells showed significantly less reactivity to both agents. Exposure of
      endothelial cells to L-glucose did not show any difference to normoglycemic
      controls. Coadministration of 20 mmol/l glucose and celiprolol demonstrated that
      the alteration of the calcium signal induced by high D-glucose concentrations
      could be significantly antagonized with celiprolol. In contrast, coincubation
      with metoprolol failed to normalize the calcium signal. This effect of celiprolol
      was completely abolished in the presence of propranolol. In normoglycemic cells,
      none of the beta-blockers influenced the intracellular calcium response to
      bradykinin or ATP. These results indicate that chronic treatment with high D
      glucose concentrations leads to an impairment of calcium signaling, which might
      be ameliorated by celiprolol.

PMID- 9519748
TI  - Expression of transforming growth factor-beta1 and type IV collagen in the renal
      tubulointerstitium in experimental diabetes: effects of ACE inhibition.
AB  - Transforming growth factor-beta (TGF-beta) and the renin-angiotensin system (RAS)
      have both been implicated in the pathogenesis of glomerulosclerosis in diabetic
      kidney disease. However, tubulointerstitial pathology may also be an important
      determinant of progressive renal dysfunction in diabetic nephropathy. In the
      present study, we investigated tubulointerstitial injury, TGF-beta1 expression,
      and the effect of blocking the RAS by inhibition of ACE. We randomized 36 male SD
      rats to control and diabetic groups. Diabetes was induced in 24 rats by
      administration of streptozotocin; 12 diabetic rats were further randomized to
      receive the ACE inhibitor ramipril (3 mg/l drinking water). At 6 months,
      experimental diabetes was associated with tubulointerstitial damage, a 70%
      increase in expression of TGF-beta1 (P < 0.05 vs. control), and a 120% increase
      in alpha1 (IV) collagen gene expression (P < 0.01 vs. control). In situ
      hybridization demonstrated a diffuse increase in both TGF-beta1 and alpha1 (IV)
      collagen mRNA in renal tubules. In addition, intense expression of both
      transcripts was noted in regions of focal tubular dilatation. Administration of
      the ACE inhibitor ramipril prevented tubulointerstitial injury and the
      overexpression of TGF-beta1 and alpha1 (IV) collagen mRNA. Changes in gene
      expression were accompanied by parallel changes in immunostaining for TGF-beta1
      and type IV collagen. The observed beneficial effects of ramipril on the
      tubulointerstitium in experimental diabetes suggest that this mechanism may
      contribute to the therapeutic effect of ACE inhibitors in diabetic nephropathy.

PMID- 9519749
TI  - Long-term treatment with the dual antithromboxane agent picotamide decreases
      microalbuminuria in normotensive type 2 diabetic patients.
AB  - Picotamide both inhibits thromboxane synthetase and acts as a thromboxane
      antagonist at the receptor level. We investigated the long-term effect of
      picotamide on urinary albumin excretion (UAE) at rest and induced by exercise in
      30 type 2 diabetic patients who were normotensive and had microalbuminuria while
      at rest. The subjects of our study had a mean age of 52.5 +/- 1.6 years, BMI of
      28.5 +/- 0.7 kg/m2, diabetes duration of 9.1 +/- 1.8 years, and HbA1c of 7.0 +/-
      0.8%. The study was a randomized double-blind placebo-controlled trial. The
      patients were randomly allocated to receive for 1 year either picotamide, 300 mg,
      3 tablets/day, or placebo, 3 tablets/day. The patients were asked to visit our
      outpatient clinic after 1, 3, 6, 9, and 12 months of treatment. At all times,
      blood pressure, microalbuminuria at rest, blood glucose, serum creatinine, serum
      picotamide, and creatinine clearance were measured; at baseline and after 6 and
      12 months, all patients underwent submaximal physical exercise. After 6 months of
      picotamide, baseline and exercise-induced microalbuminuria were significantly
      decreased (up to one-third) as compared with the baseline and placebo level, with
      no further drops at month 12 of picotamide treatment. On placebo treatment, UAE
      at rest and after exercise was slightly increased compared with baseline values.
      The effects of picotamide occurred without significant side effects or changes in
      either blood pressure levels or glycometabolic control. Our study is the first
      long-term intervention trial in type 2 diabetes showing that an antithromboxane
      agent is able to decrease microalbuminuria, which in this disease is a dual
      marker of macro- and microangiopathy. Our findings suggest an important role for
      thromboxane in the pathophysiology of microalbuminuria in diabetes; moreover, we
      hypothesize that antithromboxane agents may have a place in the
      treatment/prevention of both macro- and microvascular complications in type 2
      diabetic patients.

PMID- 9519750
TI  - Stimulatory effect of glucose on macrophage lipoprotein lipase expression and
      production.
AB  - Cardiovascular diseases are the leading cause of morbidity and mortality in
      diabetes. Lipoprotein lipase (LPL), a major secretory product of macrophages, has
      been suggested to play a key role in the development of atherosclerosis. In the
      present study, we evaluated the effect of high glucose on macrophage LPL mRNA
      expression and secretion. Exposure of murine J774 macrophages to high D-glucose
      concentrations (20-30 mmol/l) resulted in a dramatic upregulation of LPL mRNA
      expression and immunoreactive mass. This effect was not observed when these cells
      were incubated in the presence of L-glucose or mannitol. High glucose
      concentrations were also found to enhance LPL gene expression and immunoreactive
      mass in human monocyte-derived macrophages. J774 cells cultured in a high glucose
      environment expressed increased c-fos mRNA levels. Treatment of these cells with
      c-fos antisense DNA or protein kinase C inhibitor inhibited the stimulatory
      effect of glucose on LPL mRNA expression. In J774 cells exposed to high glucose
      concentrations, enhanced nuclear protein binding to the AP-1-responsive region of
      the murine LPL promoter was observed, while LPL mRNA stability remained
      unchanged. Overall, these results demonstrate that high glucose upregulates
      macrophage LPL gene expression and immunoreactive mass and that this effect
      involves transcriptional events.

PMID- 9519751
TI  - Predisposition to essential hypertension and development of diabetic nephropathy
      in IDDM patients.
AB  - Conflicting results have been reported on the relationship between familial
      predisposition to hypertension and development of diabetic nephropathy in IDDM.
      In our case-control study, we assessed the prevalence of hypertension among
      parents of 73 IDDM patients with diabetic nephropathy (DN+; persistent
      albuminuria > 200 microg/min or > 300 mg/24 h) and 73 IDDM patients without
      diabetic nephropathy (DN-; urinary albumin excretion < 20 microg/min or < 30
      mg/24 h). Arterial hypertension, defined as antihypertensive therapy or a 24-h
      ambulatory blood pressure (SpaceLabs 90207) > or = 135/85 mmHg, was present in
      57% of parents of DN+ patients compared with 41% of parents of DN- patients (P =
      0.034; difference 16% [95% CI 1.3-29.6%]). In addition, the cumulative incidence
      of hypertension was higher among parents of DN+ patients (log-rank test P <
      0.001), with a shift toward younger age at onset of hypertension in this group.
      However, the difference in prevalence of parental hypertension was not evident
      using office blood pressure measurements (64 vs. 57%; NS; difference 7% [-5.8
      20%). Furthermore, patients with DN+ and with antihypertensive therapy in both
      parents were themselves more frequently treated for hypertension than were
      patients with DN+ and without parental treatment for hypertension (100 vs. 61%; P
      = 0.034; difference 39% [21-57%]). In conclusion, familial predisposition to
      essential hypertension increases the risk of diabetic nephropathy and may also
      contribute to the development of systemic hypertension in patients with IDDM and
      diabetic nephropathy.

PMID- 9519752
TI  - Muller cell changes in human diabetic retinopathy.
AB  - Vascular cells may not be the only cells affected by diabetes in the retina. In
      particular, abnormalities of the b-wave of the electroretinogram in diabetic
      patients with absent or minimal microangiopathy have pointed to possible
      dysfunction of Muller cells, the principal glia of the retina. In this study, we
      sought evidence for diabetes-induced Muller cell abnormalities by testing the
      expression of three proteins (Bcl-2, glutamine synthetase [GS], and glial
      fibrillar acidic protein [GFAP]) that are solely or predominantly expressed in
      Muller cells and show a reproducible pattern of changes in the context of retinal
      injuries or degenerations. Retinas obtained postmortem from a total of 14 donors
      aged 65 +/- 6 years with 10 +/- 4 years of diabetes and histological evidence of
      microangiopathy and 18 age-matched nondiabetic donors were examined by
      immunohistochemistry and immunoblotting. The typical Muller cell pattern of Bcl-2
      and GS immunostaining was similar for both intensity and distribution in the
      nondiabetic and diabetic retinas, as were the levels of the two proteins. In
      contrast, GFAP staining, largely confined to the most proximal retina in the
      nondiabetic donors, was in most diabetic retinas present along the entire length
      of the Muller cell processes, throughout the outer retina. Accordingly, the level
      of GFAP was increased in the diabetic retinas (161 +/- 106 densitometric
      units/microg protein vs. 55 +/- 45 in the nondiabetic retinas, P = 0.03). These
      data provide evidence for selective biosynthetic changes of Muller glial cells in
      diabetes. Because Muller cells produce factors capable of modulating blood flow,
      vascular permeability, and cell survival, and their processes surround all blood
      vessels in the retina, a possible role of these cells in the pathogenesis of
      retinal microangiopathy deserves to be investigated.

PMID- 9519753
TI  - Unselective inhibition of endothelin receptors reduces renal dysfunction in
      experimental diabetes.
AB  - Chronic nephropathies are associated with enhanced renal synthesis of endothelin
      (ET)-1. A recent study demonstrated that an ET(A) receptor antagonist given to
      diabetic rats at the moment of disease induction prevented the development of
      renal injury. Here we investigated whether an unselective ET(A)/ET(B) receptor
      antagonist, PD 142,893, was renoprotective when given to streptozotocin diabetic
      rats when animals were already proteinuric. The effect of PD 142,893 was compared
      with that of an ACE inhibitor, lisinopril, known to retard progressive renal
      disease in experimental and human diabetes. PD 142,893 normalized systemic blood
      pressure, reduced urinary protein and albumin excretion, and ameliorated renal
      blood flow in diabetic rats, but it did not affect such parameters in control
      rats. Lisinopril had a renoprotective effect comparable to PD 142,893, although
      lisinopril controlled systemic blood pressure better. Northern blot analysis of
      ET-1 mRNA revealed upregulation of ET-1 gene in the diabetic kidney. Similar
      results were obtained by in situ hybridization in glomeruli and tubuli of
      diabetic rats. Both treatments remarkably attenuated exaggerated renal ET-1 gene
      expression. These data suggest that ET-1 is a contributory mediator of kidney
      damage in diabetes and indicate that ET receptor antagonists may represent a new
      therapeutic mean for treatment of progressive diabetic nephropathy.

PMID- 9519754
TI  - Endothelial dysfunction and the expression of endothelial nitric oxide synthetase
      in diabetic neuropathy, vascular disease, and foot ulceration.
AB  - We studied endothelial-mediated microvascular blood flow in neuropathic diabetic
      patients to determine the association between endothelial regulation of the
      microcirculation and the expression of endothelial constitutive nitric oxide
      synthetase (ecNOS) in the skin. Vasodilation on the dorsal foot in response to
      heating and iontophoresis of acetylcholine (endothelium-dependent) and sodium
      nitroprusside (endothelium-independent) were measured using single-point laser
      Doppler and laser Doppler imaging in diabetic patients with neuropathy (DN), with
      neuropathy and vascular disease (DI), with Charcot arthropathy (DA), and without
      complications (D), and in healthy control subjects (C). The response to heat was
      reduced in the DN (321 [21-629] percentage of increase over the baseline, median
      [interquartile range]) and DI (225 [122-470]) groups but was preserved in the DA
      (895 [359-1,229]), D (699 [466-1,029]), and C (810 [440-1,064], P < 0.0001)
      groups. The endothelial-mediated response to acetylcholine was reduced in the DN
      (17 [11-25]), DA (22 [2-34]), and DI (13 [2-30]) groups compared with the D (47
      [24-58]) and C (44 [31-70], P < 0.001) groups. The non-endothelial-mediated
      response to sodium nitroprusside was also reduced in the DI (4 [0-18]), DN (17 [9
      26]), and DA (21 [11-31]) groups compared with the D (37 [19-41]) and C (44 [26
      67], P < 0.0001) groups. There was a significant reduction in vasodilation in the
      DI group compared with all other groups (P < 0.0001). Full thickness skin
      biopsies from the dorsum of the foot of 15 DN, 10 DI, and 11 C study subjects
      were immunostained with antiserum to human ecNOS, the functional endothelial
      marker GLUT1, and the anatomical endothelial marker von Willebrand factor. The
      staining intensity of ecNOS was reduced in both diabetic groups. No differences
      were found among the three groups in the staining intensity of von Willebrand
      factor and GLUT1. We conclude that the endothelium-dependent and endothelium
      independent vasodilations are impaired in diabetic patients predisposed to foot
      ulceration and that neuropathy is the main factor associated with this
      abnormality. Reduced expression of ecNOS may be a major contributing factor for
      endothelial dysfunction. These data provide support for a close association of
      neuropathy and microcirculation in the pathogenesis of foot ulceration.

PMID- 9519755
TI  - Abnormalities of retinal metabolism in diabetes or experimental galactosemia: V.
      Relationship between protein kinase C and ATPases.
AB  - In the retinas of diabetic animals, protein kinase C (PKC) activity is elevated,
      and Na+-K+-ATPase and calcium ATPase activities are subnormal. These
      abnormalities are also present in another model of diabetic retinopathy,
      experimental galactosemia. We have investigated the relationship between
      hyperglycemia-induced abnormalities of PKC and ATPases using a selective
      inhibitor of beta isoform of PKC (LY333531). Diabetes or experimental
      galactosemia of 2 months' duration resulted in > 50% elevation of PKC activity in
      the retina, and administration of LY333531 prevented the elevation. In retinas of
      the same rats, the LY333531 prevented hyperglycemia-induced decreases of both Na+
      K+-ATPase and calcium ATPase activities. Retinal microvessels, the main site of
      lesions in diabetic retinopathy, likewise showed elevated activity of PKC and
      inhibition of ATPases in diabetes and in experimental galactosemia, and
      administration of LY333531 to diabetic animals prevented these abnormalities. PKC
      activity in sciatic nerves, in contrast, became subnormal in diabetes and
      experimental galactosemia, and LY333531 had no effect on PKC activity in the
      sciatic nerve. PKC activity in the cerebral cortex was not affected by diabetes
      or experimental galactosemia. The results suggest that diabetes-induced
      reductions in Na+-K+-ATPase and calcium ATPase in the retina are mediated in
      large part by PKC-beta. The availability of an agent that can normalize the
      hyperglycemia-induced increase in PKC activity in the retina should facilitate
      investigation of the role of PKC in the development of diabetic retinopathy.

PMID- 9519756
TI  - Angiotensin I-converting enzyme gene polymorphism modulates the consequences of
      in utero growth retardation on plasma insulin in young adults.
AB  - In utero growth retardation has been linked to a reduced rate of cell division in
      the fetal organs that undergo rapid growth and to permanent changes and
      adaptations (programming) that may affect the physiology in adult life. In
      particular, in utero growth retardation as reflected by a low birth weight for
      gestational age has been shown to be associated with a relative insulin
      resistance in adults. How programming may influence glucose metabolism is not
      completely understood, and the possible role of genetic factors has not been
      explored. The angiotensin I-converting enzyme gene insertion/deletion (ACE I/D)
      polymorphism may predispose to insulin resistance and modulate the expression of
      several common cardiovascular and renal disorders, especially in people with
      diabetes. The possible impact of this polymorphism on plasma glucose and insulin
      levels was investigated in a group of young adults born at term whose length or
      weight at birth were in the lowest 3% of the sex and gestational age-adjusted
      distribution (SGA, n = 172) and a group of control individuals born with an
      appropriate birth weight for gestational age (AGA, n = 207). In this study, we
      have previously demonstrated an association between SGA and relative insulin
      resistance, especially in those with shorter gestational age. In the SGA group,
      fasting plasma glucose and insulin levels were significantly correlated (R =
      0.196, P < 0.015), with this association being significant only in ACE II
      individuals (R = 0.539, P < 0.0009). In the AGA group, fasting plasma glucose and
      insulin levels were not significantly correlated. Consistent with this
      observation, the relationship between the ACE polymorphism and the insulin
      response to a glucose load was significantly heterogeneous between the AGA and
      SGA groups (P < 0.05); this was due to a tendency for ACE II individuals in the
      SGA group to exhibit increased 30-min plasma insulin levels (P < 0.05). In the
      SGA group, there was a significant interaction between gestational age and
      genotype on the insulin area (P < 0.0004); this index was inversely associated
      with gestational age in ACE II (P < 0.0005) and ACE ID (P < 0.005) subjects, but
      not in DD homozygotes (P > 0.05). The ACE D allele may thus attenuate the
      additive consequences of SGA and relatively short duration of gestation on
      insulin resistance in young adults.

PMID- 9519757
TI  - Identification and functional analysis of sulfonylurea receptor 1 variants in
      Japanese patients with NIDDM.
AB  - The sulfonylurea receptor 1 (SUR1) is an essential regulatory subunit of the beta
      cell ATP-sensitive K+ channel (K[ATP]). The possible role of SUR1 gene
      mutation(s) in the development of NIDDM remains controversial as both a positive
      association and negative linkage results have been reported. Therefore, we
      examined the SUR1 gene at the single nucleotide level with single strand
      conformation polymorphism analysis in 100 Japanese NIDDM patients. We identified
      a total of five amino acid substitutions and 17 silent mutations by examining all
      39 exons of this gene. Two rare novel mutations, D811N in exon 20 and R835C in
      exon 21, were identified in the first nucleotide-binding fold (NBF), a
      functionally important region of SUR1, in one patient each, both heterozygotes.
      To analyze possible functional alterations, we reconstituted the mutant K(ATP) by
      coexpressing beta-cell inward rectifier (BIR) (Kir 6.2), a channel subunit of
      K(ATP), and mutant SUR1 in HEK293T and COS-7 cells. As demonstrated by the patch
      clamp technique and rubidium (Rb+) efflux studies, neither mutation alters the
      properties of channel activities. Two other rare missense mutations, R275Q in
      exon 6 and V560M in exon 12, were also identified. The R275Q substitution was not
      found in 67 control subjects, and V560M was present in three control subjects.
      Neither of these substitutions appeared to cosegregate with NIDDM in the
      probands' families. A previously reported S1370A substitution located in the
      second NBF was also common in the Japanese subjects (allelic frequency 0.37), and
      was found at an equal frequency in nondiabetic control subjects. In conclusion,
      SUR1 mutations impairing K(ATP) function do not appear to be major determinants
      of NIDDM susceptibility in Japanese.

PMID- 9519758
TI  - Shortened telomere length in white blood cells of patients with IDDM.
AB  - IDDM is a polygenic and autoimmune disorder in which subsets of white blood cells
      (WBCs) are engaged in the destruction of beta-cells of the pancreas. The
      mechanisms that account for the abnormal behavior of these cells in IDDM are not
      fully understood. By measuring the mean length of telomeres of WBCs from patients
      with IDDM, we tested the concept that telomeres might play a role in IDDM. We
      examined the lengths of the terminal restriction fragments (TRFs) of DNA of WBCs
      from 234 white men comprising 54 patients with IDDM, 74 patients with NIDDM, and
      106 control subjects. When adjusted for age, the TRF length from WBCs of patients
      with IDDM was significantly shorter than that of nondiabetic control subjects
      (mean +/- SE: 8.6 +/- 0.1 vs. 9.2 +/- 0.1, P = 0.002). No significant difference
      was observed between the TRF length from WBCs of patients with NIDDM versus
      nondiabetic subjects. Neither the duration nor the complications of IDDM (i.e.,
      nephropathy and hypertension) had an effect on the TRF length of WBCs from
      patients with IDDM. The shortened TRF length of WBCs of patients with IDDM likely
      reflects a marked reduction in the TRF length of subsets of WBCs that play a role
      in the pathogenesis of IDDM.

PMID- 9519759
TI  - Novel polymorphisms in the 5' region of the LEP gene: association with leptin
      levels and response to low-calorie diet in human obesity.

PMID- 9519760
TI  - Human peroxisome proliferator-activated receptor-gamma2: genetic mapping,
      identification of a variant in the coding sequence, and exclusion as the gene
      responsible for lipoatrophic diabetes.

PMID- 9519761
TI  - Transgenic mice deficient in the LAR protein-tyrosine phosphatase exhibit
      profound defects in glucose homeostasis.
AB  - Protein-tyrosine phosphatases (PTPases) play an integral role in the regulation
      of cellular insulin action. LAR, a transmembrane PTPase expressed in insulin
      sensitive tissues, acts as a negative regulator of insulin signaling in intact
      cell models. The physiological role of LAR was studied in mice in which LAR
      expression was eradicated by insertional mutagenesis. In the fasting state, adult
      male homozygous LAR (-/-) mice had significantly lower plasma levels of insulin
      and glucose, as well as a reduced rate of hepatic glucose production compared
      with wild-type controls, suggesting a heightened level of insulin sensitivity. In
      euglycemic clamp studies, the LAR (-/-) mice exhibited a significant resistance
      to insulin-stimulated glucose disposal and suppression of hepatic glucose output.
      Examination of hepatic insulin action demonstrated that the major alteration
      involved a 47% reduction in insulin-stimulated phosphatidylinositol 3'-kinase (PI
      3-kinase) activity in the knockout mice, indicating a post-receptor signaling
      defect. Taken together with previous work on the cellular effects of LAR, the
      present results are consistent with a physiological role for LAR in the negative
      regulation of insulin action, with secondary abnormalities that contribute to the
      resistance to insulin-stimulated signaling in the knockout mice. Overall, these
      data provide further evidence for an important role for LAR in the regulation of
      insulin action and glucose homeostasis in intact animals.

PMID- 9519763
TI  - Differences in immunological response to a T. gondii protein (SAG1) derived
      peptide between two strains of mice: effect on protection in T. gondii infection.
AB  - This study presents the analysis of the immunogenicity, antigenicity and
      protective effects of a peptide derived from the major surface antigen of
      Toxoplasma gondii, SAG1. This synthetic peptide carrying three predicted H-2k
      restricted T cell epitopes was used to immunize mice. The protective effect of
      the peptide was evaluated in CBA/J and C57BL/6 mice using the decrease in brain
      cyst load as evidence of protection. Immunization of C57BL/6 mice yielded high
      antibody titres but had no protective effect after oral challenge. Immunized
      CBA/J, mice which responded with a lower titre, showed a 35% reduction in cyst
      burden after oral challenge. Both strains yielded antibodies which recognized the
      cognate SAG1 protein on immunoblot assay. Using the BIAcore, system, it was shown
      that at lower titres the CBA/J mouse sera recognized the native SAG1 protein more
      effectively than the C57BL/6 mouse sera, yielding much higher anti-peptide
      titres. Lymphoproliferation assays using the peptide experimentally confirmed the
      predicted T-cell epitopes and showed that they were also recognized by cells of
      T. gondii infected mice. The anti-peptide subclass analysis suggested a Th1
      orientation in CBA/J mice, whereas a Th2 orientation was observed in C57BL/6
      mice. Finally, fine analysis of sequences recognized under MHC class I indicated
      the existence of a T-cell epitope in the H-2k haplotype (CBA/J mice) but not in
      the H-2b haplotype (C57BL/6 mice). This study provides a structural basis to the
      understanding of the vaccination response to one of the T. gondii antigens in
      different strains of mice.

PMID- 9519762
TI  - Mutations in the promoter of adenylyl cyclase (AC)-III gene, overexpression of AC
      III mRNA, and enhanced cAMP generation in islets from the spontaneously diabetic
      GK rat model of type 2 diabetes.
AB  - Glucose-induced insulin release is decreased in the spontaneously diabetic GK
      rat, a nonobese rodent model of type 2 diabetes. Forskolin restores the impaired
      insulin release in both the isolated perfused pancreas and isolated islets from
      these rats (Abdel-Halim et al., Diabetes 45:934-940, 1996). We demonstrate here
      that the insulinotropic effect of forskolin in the GK rat is due to increased
      generation of cAMP and that it is associated with overexpression of adenylyl
      cyclase (AC)-III mRNA and gene mutations. The AC-III mRNA overexpression was
      demonstrated by in situ hybridization using oligonucleotide probes binding to
      different regions of the rat AC-III mRNA. It was associated with the presence of
      two point mutations identified at positions -28 bp (A --> G) and -358 bp (A -->
      C) of the promoter region of the AC-III gene and was demonstrable in both GK rat
      islets and peripheral blood cells. Transfection of COS cells with a luciferase
      reporter gene system revealed up to 25-fold increased promoter activity of GK AC
      III promoter when compared with normal rat promoter (P < 0.0001). In conclusion,
      forskolin restores the impaired insulin release in islets of the GK rat through
      enhanced cAMP generation. This is linked to overexpression of AC-III mRNA in GK
      islets due to two functional point mutations in the promoter region of the AC-III
      gene.

PMID- 9519764
TI  - Fas-mediated cytotoxicity induces degradation of vesicular stomatitis virus RNA
      transcripts and reduces viral titer.
AB  - Several investigators have recently examined the effect of Fas (CD95)-mediated
      apoptotic cell death on target cells (TC). The effect of Fas-mediated death on
      viral RNA within the TC, however, has not been explored. In this study, we
      investigated the ability of the Fas pathway to mediate pre-lytic degradation of
      vesicular stomatitis virus (VSV) RNA and TC RNA. We show that engagement of Fas
      antigen on VSV-infected Jurkat cells induces pre-lytic degradation of VSV RNA
      transcripts, whereas full-length VSV genome RNA, known to be tightly associated
      with viral proteins, is not degraded. Cellular RNA, including beta-actin and
      glyceraldehyde-3-phosphate-dehydrogenase mRNAs, is also degraded by Fas-mediated
      cytotoxicity. In addition, Fas-mediated cytotoxicity reduced the yield of VSV
      plaque-forming units (PFU) from Jurkat by an average of 82.0%. An anti-Fas
      blocking Ab inhibited the RNA degradation and restored the number of VSV PFU to
      near control levels. These data indicate that the Fas lytic pathway could play a
      role in the elimination of viruses through degradation of intracellular viral
      RNA. reserved

PMID- 9519765
TI  - A Shannon entropy analysis of immunoglobulin and T cell receptor.
AB  - In 1970, before any antigen-bound immunoglobulin structure had been solved, Elvin
      Kabat proposed that regions of high amino acid diversity would be the antigen
      binding sites of immunoglobulin (Kabat, 1970). Conversely, sites of low
      variability were proposed to be structural, framework regions. This variability
      was defined by Wu and Kabat as the number of different amino acids found at a
      site divided by the relative frequency of the most common amino acid at that site
      (Wu and Kabat, 1970). Several groups have subsequently devised improvements of
      Kabat-Wu variability analysis (Litwin and Jores, 1992). While these methods are
      somewhat better than Kabat-Wu, they still suffer from Kabat-Wu's basic
      limitation: they account for only the most common one or two amino acids in
      estimating diversity. This leads to underestimates of low diversities and
      exaggerations of high diversities. Shannon information analysis eliminates
      serious bias and is more stable than Kabat-Wu and second generation measures of
      diversity (Jores et al. 1990; Wu and Kabat, 1970). Statistical reliability can be
      measured using Shannon analysis, and Shannon measurements can be provided with
      error estimates. Here we use Shannon's method to analyze the amino acid diversity
      at each site of T cell receptor Valpha and Vbeta to identify complementarity
      determining regions and framework sites. Our results reveal that the T cell
      receptor is significantly more diverse than immunoglobulin-suggesting T cell
      receptor has more than the previously-discovered four complementarity determining
      regions. These new complementarity determining regions may represent a larger
      antigen combining site, additional combining sites, or an evolutionary strategy
      to avoid inappropriate interaction with other molecules.

PMID- 9519766
TI  - DNA hydrolysis by monoclonal anti-ssDNA autoantibody BV 04-01: origins of
      catalytic activity.
AB  - Monoclonal anti-DNA autoantibody BV 04-01 catalyzed hydrolysis of DNA in the
      presence of Mg2+ ions. DNA hydrolyzing activity was associated with BV 04-01 IgG,
      Fab, and SCA 04-01 proteins. Pronounced cleavage specificity for both ss and
      dsDNA was observed with efficient hydrolysis of the C-rich region of the
      oligonucleotide A7C7ATATAGCGCGT7 as well as preference for cleavage within CG
      rich regions of double-stranded DNA. Data on specificity of ssDNA hydrolysis and
      kinetic data obtained from wild-type SCA 04-01 and two SCA 04-01 mutants (L32Phe
      and L27dHis) were used to model the catalytically active antibody site utilizing
      the previously resolved X-ray structure of (dT)3 liganded Fab 04-01. The
      resulting model suggested that BV 04-01 activates the target phosphodiester bond
      by induction of conformational strain. In addition, the antibody-DNA complex
      contained a potential Mg2+ ion coordination site composed of the L32Tyr and
      L27dHis amino acid side chains and a DNA 3'-phosphodiester group. Induction of
      strain and metal coordination could be constituents of a mechanism by which this
      antibody catalyzed DNA hydrolysis. Sequence data for BV 04-01 VH and VL genes
      suggested that the proposed catalytic antibody active site was germ-line encoded.
      This observation suggests the hypothesis that catalytic activity might represent
      an important but unspecified function of some antibody molecules.

PMID- 9519767
TI  - Ig V region hypermutation in B cell hybrids mimics in vivo mutation and allows
      for isolation of clonal variants.
AB  - In order to investigate the regulation of Ig hypermutation, we have established a
      cell culture system in which reversion of a V region stop codon in a stably
      transfected Ig gene permits the quantitation of mutation rates by fluctuation
      analysis. Transfected heavy chain V regions associated with the mu constant
      region undergo low rates of mutation in the NSO plasmacytoma cell line and a
      moderate rate of mutation in the 18.81 pre-B cell line. Most of the hybrids
      created by fusing these two cell lines resembled the non-permissive NSO cell
      line, though a few hybrids had constitutive V region mutation rates that were
      even higher than 18.81 and similar to the high rates of mutation that occur in
      vivo (Green, N. S., Rabinowitz, J. L., Zhu, M., Kobrin, B. J. and Scharff, M. D.
      (1995) Proc. Nat. Acad. Sci. (USA) 92, 6304 6308). Characterization of these
      hybrids now demonstrates that the transfected genes were integrated outside of
      the Ig locus. Mutation was due to multiple single base pair replacements in the V
      region and not the C region, was ongoing and often arose in hot spot motifs
      described by V region hypermutation in vivo. Subcloning of unstable hybrids
      allowed for the isolation of highly related clones with 44-70-fold different
      mutation rates. These results suggest that V region hypermutation in this mode in
      vitro systems is under both positive and negative regulation.

PMID- 9519768
TI  - Clonal origin of leukemia--revisited. A tribute to Philip J Fialkow, MD.

PMID- 9519769
TI  - Clonal development of myeloproliferative disorders: clues to hematopoietic
      differentiation and multistep pathogenesis of cancer.
AB  - In November 1996, word reached the University of Washington that Philip Fialkow
      and his wife, Helen, had died while trekking in Nepal. Over a 30-year period, Dr
      Fialkow and his colleagues used the cellular mosaicism resulting from X
      chromosome inactivation in females as a marker system to investigate the clonal
      development of human hematopoietic disorders. This review discusses the impact
      that these studies have had on our understanding of hematopoietic stem cell
      relationships and the pathogenesis of human neoplasia in general. To appreciate
      the special role played by studies on clonality, it is necessary to consider how
      little was known about the origin of leukemias and myeloproliferative disorders
      and the limited techniques available for their study in the early to mid 1960s.
      Dr Fialkow and his coworkers were the first to show that myeloproliferative
      disorders and acute myelogenous leukemias (AML) are clonal diseases at the time
      of diagnosis and to elucidate the level of differentiation manifested by the
      originating cell type. Although the myelodysplastic disorders were found to
      involve a pluripotent stem cell, heterogeneity was found in the level of stem
      cell involvement in AML. Evidence was obtained to support a multistep
      pathogenesis of these diseases as well as a clonal but cytogenetically normal
      stage in some cases of Ph-positive chronic myelogenous leukemia, AML, acute
      lymphoblastic leukemia and myelodysplasia.

PMID- 9519770
TI  - Clonality studies in acute myeloid leukemia.
AB  - The study of X-chromosome inactivation patterns (XCIPs) to determine tumor
      clonality was established by Fialkow using G6PD protein isoenzymes but was
      limited by the low frequency of heterozygotes. Analysis was extended to most
      females with the demonstration of differential DNA methylation patterns on active
      and inactive X-chromosome alleles and uses Southern blotting or PCR of either
      restriction enzyme polymorphisms, eg PGK, HPRT, or variable number tandem repeat
      sequences, eg M27beta, HUMARA. More recently RNA polymorphisms have been reported
      enabling direct analysis of expressed transcripts from the two alleles.
      Interpretation of clonality requires knowledge of an individual's constitutive
      XCIP as skewing (>75% expression of one allele) occurs in a significant
      proportion of hematologically normal females, probably due to the stem cell pool
      size at the time of Lyonization. Furthermore, acquired skewing occurs with
      increasing age. For myeloid disorders in the young, T lymphocytes serve as a
      suitable control XCIP, but interpretation of imbalanced XCIPs in the elderly can
      be difficult. In AML, XCIPs at presentation are consistent with a clonal disorder
      whereas in remission comparison with normal controls suggests that true clonal
      remission is infrequent. Sequential analysis of samples may be helpful in some
      patients in order to determine evolving clonal populations.

PMID- 9519771
TI  - Multiple myeloma: the cells of origin--a two-way street.
AB  - Multiple myeloma results from an interplay between the monoclonal malignant
      plasma cells and supporting nonmalignant cells in the bone marrow. Recent studies
      suggest that the final transforming event in this B cell disorder occurs at a
      late stage of B cell differentiation based on the characteristics of the
      immunoglobulin genes expressed by the malignant clone as well as surface markers
      present on the tumor cells. Recently, an increasing pathogenic role in this
      malignancy by the nonmalignant cells in the bone marrow has been suggested by
      several studies. Specific infection of these supporting cells by the recently
      identified Kaposi's sarcoma-associated herpes virus (KSHV) suggests a novel
      mechanism by which this nonmalignant population may lead to the development of
      this B cell malignancy and support its growth.

PMID- 9519773
TI  - Chronic myelogenous leukemia: too much or too little growth, or both?
AB  - CML, characterized by the BCR/ABL gene rearrangement has been more extensively
      studied than any other malignancy. Over the last decade, significant progress has
      been made in our understanding of BCR-ABL-induced alterations in intracellular
      signaling. Unfortunately, we still only poorly understand the correlation between
      the clinical symptoms of chronic phase CML and the BCR-ABL oncoprotein. This is
      in part due to lack of a good in vivo animal model of chronic phase CML. In vivo
      and in vitro studies from the Clarkson group, recently reviewed in this journal
      (Leukemia 1997; 11: 1404-1428), have significantly enhanced our understanding of
      the pathophysiology of CML. However, further characterization of the effect of
      the BCR-ABL oncoprotein on signal molecules involved with cell differentiation,
      cell proliferation, cell survival and cell adhesion in primary Ph+ CML
      progenitors or in vivo models of CML will be needed to provide a full
      understanding of the pathophysiology of chronic phase CML.

PMID- 9519772
TI  - X-inactivation analysis in the 1990s: promise and potential problems.

PMID- 9519774
TI  - An evaluation of combinations of diaziquone, etoposide and mitoxantrone in the
      treatment of adults with relapsed or refractory acute myeloid leukemia: results
      of 8722, a randomized phase II study conducted by Cancer and Leukemia Group B.
AB  - A phase II trial was conducted to determine which of the three possible two-drug
      combinations of diaziquone, etoposide and mitoxantrone was associated with the
      highest response rate in patients with relapsed or refractory acute myeloid
      leukemia (AML). Of the 167 patients (median age 55) with AML who entered the
      trial, 123 were in first relapse, 22 were in second relapse and 22 had failed to
      achieve complete remission (CR). CR rates were 30% for diaziquone and
      mitoxantrone, and 23% for the other two combinations (mitoxantrone/etoposide and
      diaziquone/etoposide), NS. Patients in first relapse had higher CR rates (40%)
      than other patients. Of the 166 patients who actually received treatment, 43 died
      before having either a CR or persistent leukemia. Non-hematologic toxicity was
      primarily mucosal with 24% of patients experiencing grade 3 or greater stomatitis
      on the two diaziquone arms, and 43% on the mitoxantrone/etoposide arm. The
      combination of diaziquone and mitoxantrone was selected for further testing in
      patients with AML.

PMID- 9519775
TI  - Estimated 6-year event-free survival of 55% in 60 consecutive adult acute
      lymphoblastic leukemia patients treated with an intensive phase II protocol based
      on high induction dose of daunorubicin.
AB  - On the basis of a previous experience suggesting that daunorubicin dose in
      induction was an independent prognostic factor in adult ALL, we designed a
      chemotherapeutic regimen (ALLVR589) characterized by high doses of daunorubicin
      (270 mg/m2) in induction and by high-dose Ara-C in post-remission. The protocol
      was otherwise conventional: induction and post-remission therapy were followed by
      chemo-radio prophylaxis of the central nervous system (CNS) and periodical
      reinductions over a 3-year maintenance period. Sixty consecutive patients (male
      42, female 18, median age 34 years, range 14-71; B-lineage, 35; T-lineage, 25;
      Ph' and bcr/abl positive, 7) recruited between 1989 and 1996, were evaluated for
      treatment outcome. Complete remissions were 56 (93%), one patient had refractory
      disease, early deaths were five (8%); 19/56 (34%) patients relapsed, five of whom
      were Ph'+. Median time to relapse was 11 months (range 3-47); 68% of relapses
      occurred within 12 months from CR. No CNS relapses were observed. After a median
      follow-up of 44 months (1-100), 33/60 (55%) patients remain event-free; 23/60
      (38%) are off-therapy in continuous CR (median follow-up from diagnosis: 63
      months; range 38-100). These results suggest that increasing DNM dosage in
      induction is one of the possible approaches to improve the outcome of adult ALL
      by decreasing the relapse occurrence.

PMID- 9519776
TI  - Induction of clinical remission in T-large granular lymphocyte leukemia with
      cyclosporin A, monitored by use of immunophenotyping with Vbeta antibodies.
AB  - A 54-year-old woman presented with a severe autoimmune anemia, thrombocytopenia,
      neutropenia (Evans' syndrome), and CD8+ lymphocytosis, without signs of
      lymphadenopathy or splenomegaly. A diagnosis of T cell large granular lymphocyte
      (T-LGL) leukemia was made, based on cytomorphology, the typical CD3+/CD4
      /CD8+/CD16+/CD56-/CD57-/HLA-DR(+/-) immunophenotype of the lymphocytosis (9 x
      10(9)/l), and biallelic clonally rearranged T cell receptor beta (TCR beta)
      genes. Clonality of the TCR alphabeta+ T-LGL was also demonstrated with a panel
      of antibodies against variable domains of TCR beta chains, which showed single
      Vbeta7.1 expression on the CD3+ T-lymphocytes. After treatment failure with
      corticosteroids, splenectomy, and cyclophosphamide, respectively, a complete
      clinical remission was induced and sustained with cyclosporin A. Vbeta7.1/CD8/CD3
      triple immunofluorescence stainings appeared to be valuable for titrating the
      cyclosporin A dosage by monitoring the T-LGL cells during treatment.

PMID- 9519777
TI  - Evidence for specific immune response against P210 BCR-ABL in long-term remission
      CML patients treated with interferon.
AB  - Interferon-alpha treatment induces complete cytogenetic remission in 25% of
      Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia (CML)
      patients. These remissions are durable unlike remissions induced with other
      therapies and yet residual leukemia is detectable in most of these patients.
      Total peripheral blood mononuclear cells (PBMCs) from CML patients in long-term
      remission following interferon treatment exhibited significantly higher
      proliferative responses (four- to 15-fold over background) than normals directed
      against P210 BCR-ABL in extracts of transfected monkey fibroblast cells.
      Surprisingly, similar enhanced levels of specific proliferative responses were
      observed with extracts from cells expressing Bcr and/or Abl proteins. In
      contrast, extracts from vector only or v-Mos-expressing cells had background
      level responses. Control monkey fibroblast cells lacking BCR-ABL expression
      failed to induce proliferation over background levels. Normal individuals had no
      significant responses to Bcr/Abl extracts. On the other hand, peripheral blood
      mononuclear cells from allogeneic bone marrow transplant CML patients had
      proliferative responses to cell extracts independent of Bcr-Abl. These data
      indicate that patients in remission due to alpha-interferon treatment have
      significantly higher levels of specific cellular immunoreactivity against Bcr/Abl
      sequences than normal controls, which could play a role in maintaining
      cytogenetic remission in Ph-positive CML patients.

PMID- 9519779
TI  - Elevated expression of the proto-oncogene c-kit in patients with mastocytosis.
AB  - The stem cell factor (SCF)c-kit receptor interaction plays a critical role in the
      development and survival of mast cells. Several studies have also associated c
      kit receptor mutations with the human diseases, mastocytosis and piebaldism.
      Overexpression of c-kit has been reported to be associated with
      myeloproliferative disorders and myelodysplastic syndromes. Using peripheral
      blood mononuclear cells (PBMCs) from 11 patients with indolent mastocytosis
      (category I), mastocytosis with an associated hematologic disorder (category II),
      or aggressive mastocytosis (category III); a patient with CMML unassociated with
      mastocytosis, and PBMCs from 13 normal subjects, we examined the level of
      expression of c-kit mRNA along with other c-kit isoforms to determine if
      overexpression of the c-kit receptor was associated with mastocytosis. Using
      quantitative competitive PCR, c-kit mRNA levels on average were found to be
      statistically elevated in the five patients with mastocytosis with an associated
      hematologic disorder and in the patient with aggressive mastocytosis as compared
      with controls, but not elevated in patients with indolent mastocytosis. The
      relative mRNA expression for the two c-kit isoforms was not significantly
      different in the mastocytosis patients compared with controls. This demonstration
      of the overexpression of c-kit mRNA in mastocytosis, and particularly those
      patients with clinical evidence of myelodysplastic syndrome, adds evidence to
      support the conclusion that mastocytosis, at least in some patients, is a feature
      of myelodysplasia; and suggests that determination of c-kit mRNA expression in
      PBMCs may provide an additional approach to assessing prognosis.

PMID- 9519778
TI  - Interferons and retinoids enhance and dexamethasone suppresses urokinase-mediated
      plasminogen activation in promyelocytic leukemia cells.
AB  - All-trans retinoic acid (RA) has been successfully used in the treatment of
      patients with acute promyelocytic leukemia (APL). It induces differentiation of
      APL cells and reduces the bleeding tendency in APL patients. It has been proposed
      that plasminogen activation could affect the fibrinolytic balance in patients
      with leukemia. In our earlier study we found that treatment of APL cells with RA
      results in changes in urokinase (uPA) production. As interferons (IFNs) and
      dexamethasone can be used together with RA in the treatment of patients with APL,
      we have now studied the effects of RA together with IFNs and dexamethasone on the
      plasminogen activation cascade of these cells, including measurement of plasmin
      generation and uPA receptor (uPAR), using enzyme immunoassays, fluorescence
      activated cell sorter analysis and RNA extraction with Northern blotting. Our
      main results were: (1) plasmin was formed on the surface of APL cells; (2) RA
      stimulated transiently plasmin generation and increased uPAR mRNA level; (3) IFNs
      alpha and gamma potentiated RA in its effects on uPA and plasmin activities and
      on uPAR level; (4) dexamethasone suppressed totally the effect of RA on uPA
      induction and plasminogen activation; and (5) IFNs and dexamethasone alone did
      not have potent effects on plasminogen activation. These results may assist in
      the design of therapy for APL patients.

PMID- 9519780
TI  - Pediatric acute myelogenous leukemia cells express IL-6 receptors and are
      sensitive to a recombinant IL6-Pseudomonas exotoxin.
AB  - We have studied IL-6 receptor (IL-6R) expression on AML cells from 15 pediatric
      patients by immunocytochemistry/flow cytometry, reverse-transcription polymerase
      chain reaction, and Scatchard analysis. High-affinity IL-6R were detected on
      leukemic cells from 12 (80%) patients. Binding sites per cell ranged from 140 to
      3580 (median 920; mean 1240), with dissociation constants of 0.26 to 0.71 nM. We
      therefore assessed the in vitro sensitivity of IL-6R+ AML cells to treatment with
      a recombinant IL6-Pseudomonas exotoxin fusion protein (IL6-PE4E), using the XTT
      cytotoxicity assay. Leukemic cells from eight patients had ID50 values
      (concentration of IL6-PE4E producing a 50% decrease in cell viability) of <1000
      ng/ml (median, 87 ng/ml; mean, 262 ng/ml). Sensitivity to IL6-PE4E correlated
      significantly with receptor number. Normal bone marrow mononuclear cells had
      undetectable IL6-R expression (<20 receptors/cell) and were relatively resistant
      to IL6-PE4E. To test the efficacy of IL6-PE4E for ex vivo purging in an
      autologous stem cell transplantation setting, we incubated primary IL-6R+ AML
      cells with 10(3) ng/ml IL6-PE4E for 24 h, followed by inoculation into SCID mice.
      Mice receiving treated cells showed no leukemic engraftment, while all mice
      receiving untreated or control-treated cells developed leukemia with a median
      presymptomatic interval of 55 days. In recipients of IL6-PE4E treated cells, no
      evidence of occult leukemia was detected by PCR analysis of blood and bone marrow
      cells at 185 days postinoculation. These data suggest that IL-6R are expressed on
      leukemic cells from a substantial percentage of pediatric AML patients.
      Furthermore, leukemic cells expressing high numbers of IL6-R may be sensitive to
      IL6-PE4E in an ex vivo purging protocol.

PMID- 9519781
TI  - Acute myeloid leukemia cells with low P-glycoprotein expression and high
      rhodamine 123 efflux capacity display high clonogenicity.
AB  - This study was designed to correlate the clonogenic capacity of acute myeloid
      leukemia (AML) cells with P-glycoprotein (P-gp) expression level and P-gp
      mediated efflux capacity. Fifty AML cell samples were tested for P-gp expression
      using MRK16 monoclonal antibody and flow cytometry. Among them, 12 samples were
      selected for sorting experiments according to the following two criteria: their
      clonogenic capacity in methylcellulose in the presence of 5637 conditioned
      medium, and the heterogeneity of P-gp distribution in leukemic cells. For each of
      these 12 samples, leukemic cells which displayed the highest P-gp expression
      level (P-gp++) and P-gp- leukemic cells were sorted after MRK16 staining and
      seeded into methylcellulose for primary clonogenic assay. In each case, the
      number of CFU-L in the P-gp fraction was significantly higher than that of the P
      gp++ fraction (P < 0.01); the median number of CFU-L for 10(5) seeded cells being
      147 (range 3-1855) and 495 (range 60-4100) for P-gp++ and P-gp- populations,
      respectively. Furthermore, in order to correlate clonogenic capacity and P-gp
      function, AML cells were stained with rhodamine 123 (Rh 123), washed and then
      sorted after 4 h incubation at 37 degrees C in Rh 123-free media on the basis of
      their residual fluorescence intensity before plating. For each of six samples, we
      found that the number of CFU-L in the AML cell fraction which displayed the most
      efficient Rh 123 efflux capacity (Rh 123dull) was significantly higher compared
      to that of the AML cell fraction which displayed high residual fluorescence
      signal (Rh 123bright) (P = 0.05); the median number of CFU-L for 10(5) seeded
      cells being 1025 (range 250-2240) and 296 (range 11-838) for Rh 123dull and Rh
      123bright populations, respectively. Altogether this study suggests that, for an
      individual AML cell population, the clonogenic fraction is preferentially
      recruited in AML cells which display low P-gp expression and high P-gp-mediated
      efflux capacity.

PMID- 9519782
TI  - Reduced Tyk2/SHP-1 interaction and lack of SHP-1 mutation in a kindred of
      familial hemophagocytic lymphohistiocytosis.
AB  - Familial hemophagocytic lymphohistiocytosis (FHLH) is an autosomal recessive
      disease with features similar to those of the murine motheaten phenotype
      resulting from mutations of protein tyrosine phosphatase SHP-1. This has raised
      the possibility that defects in SHP-1 or SHP-1-regulated signaling molecules may
      be present in FHLH. In this study, we examined SHP-1 protein and transcript in
      the peripheral blood mononuclear cells (PBMC) of an FHLH family. Our results show
      that the FHLH patient and the parents express comparable levels of a single SHP-1
      protein and that the SHP-1 cDNA clone from the patient contains no mutation in
      the coding region. Interestingly, a reduced association of SHP-1 with the Jak
      family kinase Tyk2 was detected in the patient and the defect appears to have
      been inherited from one of the parents. This reduced SHP-1/Tyk2 association is
      likely due to a defect in Tyk2 or in cellular factors regulating Tyk2, because we
      found no abnormalities in SHP-1 or in SHP-1 association with the other Jak
      kinases. These data demonstrate that the SHP-1 gene is intact in FHLH and that
      the defect in some cases with this disease may involve signaling molecules
      regulated by SHP-1.

PMID- 9519783
TI  - Forced expression of Genesis, a winged helix transcriptional repressor isolated
      from embryonic stem cells, blocks granulocytic differentiation of 32D myeloid
      cells.
AB  - We recently isolated and characterized a novel member of the winged helix
      (formerly HNF-3/Forkhead) transcriptional regulatory family, termed Genesis.
      Genesis was found to be a transcriptional repressor expressed almost exclusively
      in embryonic stem cells or embryonal carcinoma cells. This expression rapidly
      declined when these cells were stimulated to differentiate. This expression
      pattern suggested that Genesis may play a role in cellular differentiation. To
      explore that possibility in a heterologous system of differentiation, Genesis was
      stably transduced into the IL-3-dependent myeloid cell line 32D using a
      retroviral expression vector. 32D cells overexpressing Genesis failed to mature
      normally when stimulated with G-CSF but continued to proliferate and maintained a
      primitive phenotype. This finding implicates Genesis in the regulation of
      development, and also implies that there may be common transcription pathways for
      many developing tissues.

PMID- 9519784
TI  - Primary cutaneous large-cell lymphoma: analysis of 49 patients included in the
      LNH87 prospective trial of polychemotherapy for high-grade lymphomas. Groupe
      d'Etude des Lymphomes de l'Adulte.
AB  - The objectives of this study were to evaluate the outcome after polychemotherapy
      for patients with primary cutaneous large-cell lymphomas (PCLL) and to validate
      the recently proposed immunohistologic classification of cutaneous lymphomas.
      Among 140 patients with positive skin biopsies included in the LNH87 protocol
      (for treatment of aggressive lymphomas), 49 patients met the criteria of PCLL.
      Characteristics were: sex ratio M/F, 2.3; age 18 to 83 years (median, 52),
      peripheral lymph nodes, n=22; diffuse disease, n=12; median tumor size, 4.5 cm;
      elevated lactate dehydrogenase, n=9; ECOG: 0/1, n=49. Histology was: follicular
      center B cell, n=23; B-lymphoblastic, n=1; anaplastic large-cell lymphoma, n=14
      (T cell phenotype n=8); CD30- T cell lymphoma, n=11. All patients received
      polychemotherapy: under 70 years, ACVBP (three to four cycles and consolidation
      for 6 months) n=25; mBACOD (eight cycles) n=16; over 70 years, C(T)VP (six
      cycles) n=8. Radiation therapy was not included in the protocol. With a median
      follow-up of 5 years, 24/49 patients had relapsed, with 20 skin relapses. Event
      free (EFS) and overall survival (OS) at 5 years were, respectively, 50 and 77%.
      Significant adverse prognostic factors were: histology (CD30- T cell lymphoma)
      and diffuse cutaneous disease (>10% of skin). The presence of nodal involvement
      was only significant for EFS. When compared to 140 non-cutaneous lymphoma
      patients included in the same trial and fully matched for the main clinical
      characteristics, OS was similar. In conclusion, PCLL behaves like other localized
      B or T cell extranodal lymphomas with the same prognostic factors (LDH, ECOG,
      age) except for CD30+ PCLL which have a very good prognosis.

PMID- 9519785
TI  - In vitro cytoreductive effects on multiple myeloma cells induced by
      bisphosphonates.
AB  - In a double blind randomized study, the bisphosphonate drug Pamidronate (Aredia)
      significantly protected Durie-Salmon stage III multiple myeloma patients from
      osteolytic bone disease. In the patient sub-group on salvage chemotherapy.
      Pamidronate treatment was also significantly associated with prolonged survival.
      To test if this drug could induce direct antitumor effects, we exposed myeloma
      cells to increasing concentrations of Pamidronate or a more potent
      bisphosphonate, Zoledronate. A concentration- and time-dependent cytotoxic effect
      was detected on four of five myeloma cell lines as well as three specimens
      obtained directly from myeloma patients. Zoledronate-induced cytotoxicity was
      significantly greater than that of Pamidronate. Cytotoxicity could not be
      explained by bisphosphonate-induced chelation of extracellular calcium or
      secondary decrease in production of the myeloma growth factor interleukin-6.
      Morphological examination, DNA electrophoresis and cell cycle analysis indicated
      that the bisphosphonate-induced cytotoxic effect consisted of a combination of
      cytostasis and apoptotic myeloma cell death. Enforced expression of BCL-2
      protected against the apoptotic death but not against cytostasis. Most cytotoxic
      effects were seen between 10 and 100 microM of drug. The results suggest a
      possible direct anti-tumor effect in myeloma patients treated with
      bisphosphonates which may participate in their significantly increased survival.
      This hypothesis should now be further tested in clinical trials.

PMID- 9519786
TI  - A novel BCR-ABL rearrangement in a Philadelphia chromosome-positive chronic
      myelogenous leukaemia variant with thrombocythaemia.
AB  - Reverse transcription polymerase chain reaction was used to detect an unusual
      BCR/ABL transcript in a patient who presented with thrombocythaemia and was
      Philadelphia chromosome positive but weakly reactive to conventional BCR/ABL
      fusion probes. Sequencing revealed the presence of a 12 bp insert between BCR
      exon2 (b2) and ABL exon2 (a2). In such cases the use of conventional BCR/ABL
      probes may lead to false negative results. This is the first report of this
      transcript. Clinically the patient has responded well to therapy.

PMID- 9519787
TI  - Pseudo-Gaucher histiocytes identified up to 1 year after transplantation for CML
      are BCR/ABL-positive.
AB  - The results of polymerase chain reaction (PCR) analysis after transplantation for
      chronic myelogenous leukemia (CML) are difficult to interpret clinically.
      Positive findings for BCR/ABL can be seen not only in patients who go on to
      relapse but also in patients who, after years of follow-up, remain in complete
      remission. The cause for the lack of concordance between PCR findings and relapse
      is not clear. We identified two patients with CML who had rare pseudo-Gaucher
      cells in their bone marrow aspirate specimens prior to, and at 1, and 6 or 12
      months following syngeneic or allogeneic hematopoietic transplantation. After the
      transplant, the patients obtained clinical remission and were shown to be
      cytogenetically normal and to have germline MBCR in blood or bone marrow by
      Southern analysis. One patient was PCR-positive for BCR/ABL in the marrow at 12
      months. In order to determine whether the pseudo-Gaucher histiocytes were BCR/ABL
      positive, we used fluorescence in situ hybridization and probes for MBCR and ABL
      and analyzed Wright-stained smears to correlate molecular cytogenetic findings
      with cell type. On three aspirate smears from each patient (at 6 or 12 months
      post-transplant), all of the pseudo-Gaucher cells studied (10/10 in one patient
      and 12/12 in the other) showed the fusion for BCR/ABL. Other cells analyzed
      randomly (erythroid precursors, granulocytes and rare monocytes, lymphocytes and
      plasma cells) did not. Our cases provide the first proof that pseudo-Gaucher
      cells carry the BCR/ABL fusion. Furthermore, they illustrate that these cells can
      be found in the marrow for up to 12 months following transplantation. Our results
      permit speculation that pseudo-Gaucher cells or other long-lived histocytes may
      be one cause of persistent PCR positivity after transplantation that is not
      predictive of disease relapse.

PMID- 9519788
TI  - Myelodysplasia during the course of myeloma. Restriction of 17p deletion and p53
      overexpression to myeloid cells.
AB  - We report a case of myelodysplastic syndrome (MDS) occurring during the course of
      multiple myeloma (MM) treated by alkylating agents. Karyotype showed unbalanced
      t(5;17), resulting in 17p deletion. Dysgranulopoiesis typical of the '17p
      syndrome' and p53 mutation and overexpression were present. A combination of FISH
      and immunophenotype analysis (FICTION, analysis) showed that 17p deletion was
      restricted to myeloid cells, and that p53 overexpression was also restricted to
      myeloid cells. These findings strongly argue against a common clonal origin of MM
      and MDS, and support the hypothesis that MM and MDS were clonally unrelated, and
      that MDS was indeed secondary to treatment with alkylating agents.

PMID- 9519789
TI  - DNA in situ hybridization of individual colonies to determine lineage derivation
      in leukemia.
AB  - The degree of lineage commitment of the hematopoietic stem cell in chronic
      myelomonocytic leukemia (CMML) and in acute myelogenous leukemia (AML) remains
      debatable and may be heterogeneous depending on the patient subgroup. In this
      study, we have used a modification of DNA in situ hybridization which adapts this
      technique to the analysis of karyotype in single hematopoietic colonies. By
      utilizing a digoxigenin-labeled chromosome 7 probe, we demonstrate that, in
      patients with monosomy 7, both erythroid and myelomonocytic progenitors can be
      karyotypically aberrant. In addition, significant levels of diploid clonogenic
      cells persist (as reflected by the presence of between 14% and 43% diploid
      colonies) despite the detection of only monosomy 7-bearing bone marrow metaphases
      as assessed by standard cytogenetic techniques. Our observations demonstrate that
      digoxigenin-based DNA in situ hybridization (DISH) can be performed on
      individually microaspirated colonies for determination of lineage derivation.
      This technique may also be applicable to the detection of minimal residual
      disease with clonogenic potential and for assessing the interaction between
      normal and leukemic precursors.

PMID- 9519790
TI  - Autoreactive B cell clones in marginal-zone B cell lymphoma (MALT lymphoma) of
      the stomach.

PMID- 9519791
TI  - Does EBV RNA modulate ADA mRNA translation?

PMID- 9519792
TI  - A new case of chronic myeloid leukemia (CML) in myeloid blast crisis with an
      atypical (b3/a3) junction of the BCR/ABL gene.

PMID- 9519793
TI  - TCR-gamma gene rearrangement with interstitial deletion within the TRGV2 gene
      segment is not detected in normal T-lymphocytes.

PMID- 9519794
TI  - Protective effects of Mu-Fang-Ji-Tang against myocardial injury in a murine model
      of congestive heart failure induced by viral myocarditis.
AB  - The effects of Mu-Fang-Ji-Tang (TJ-36), a traditional Chinese herbal medicine,
      were studied in a murine model of congestive heart failure induced by viral
      myocarditis. In the group of animals treated with Mu-Fang-Ji-Tang in a dose of
      1.5g/kg/day, the heart weight to body weight ratio was significantly lower than
      in the control group (p<0.01). Histopathological grades were also significantly
      lower in the Mu-Fang-Ji-Tang treated group than in the placebo group (p<0.05).
      Furthermore, survival was increased in the Mu-Fang-Ji-Tang treated group, versus
      the control group (p<0.05). In vitro, murine J774A.1 macrophages inoculated with
      encephalomyocarditis virus produced a significantly greater amount of nitrites
      compared to non-activated macrophages. Mu-Fang-Ji-Tang added to the cells (25,
      50, 75, 100 microg/ml) concomitantly with the encephalomyocarditis virus
      inhibited nitrite formation in a concentration-dependent manner. Mu-Fang-Ji-Tang
      showed a protective effect against myocardial injury leading to congestive heart
      failure in this animal model.

PMID- 9519795
TI  - Catalase prevents estradiol-induced chondrocyte cytotoxicity.
AB  - Osteoarthritis is a common geriatric disease and estrogen may play an important
      role in this disease. Estradiol may cause chondrocyte damage as suggested by in
      vitro and in vivo data. One of the possible mechanisms of estradiol-induced
      chondrocyte damage was thought to be related to free radicals. Whether catalase,
      a known free radical scavenger, can prevent estradiol-induced chondrocyte damage
      was tested using a chondrocyte culture system. The results of this study suggest
      that catalase can significantly reduce the estradiol-induced damage to
      chondrocytes. Apparently, catalase alters the molecular structure of estradiol as
      indicated by the absorption spectrum of estradiol with time. The modified
      estradiol may decrease its toxicity to the chondrocytes. However, the contents of
      free radicals in the treated chondrocytes have no significant difference from the
      untreated control cells. Studies to further investigate the mechanism or
      prevention of estradiol-induced chondrocyte damage in osteoarthritis are
      warranted.

PMID- 9519796
TI  - C-fos expression pattern in the hypothalamus and the preoptic area of the rat
      during proestrus.
AB  - c-fos gene expression in the hypothalamus, the preoptic area, the hippocampus and
      the frontal cerebral cortex of the rat was determined every two hours from 09:00
      h to 19:00 h on the day of proestrus by using reverse transcription coupled to
      polymerase chain reaction. Rats under a 14:10 h light-dark cycle, with lights on
      at 06:00 h were used. We found a marked increase in c-fos gene expression in the
      studied regions but the hippocampus at 13:00 h, followed by a significant
      diminution in the subsequent hours of proestrus day. The high expression of c-fos
      gene at 13:00 could be associated to the increase in estradiol seric levels
      observed both at 11:00 h and at 13:00 h. Our results correlate with the increase
      in the number of FOS immunoreactive cells in some forebrain areas in proestrus
      afternoon related to gonadotropin releasing hormone secretion.

PMID- 9519797
TI  - Effects of haloperidol and GM1 ganglioside treatment on striatal D2 receptor
      binding and dopamine turnover.
AB  - Previous studies have shown that whereas exogenous GM1 ganglioside co
      administration leads to an increase of haloperidol-induced behavioral
      supersensitivity, GM1 significantly attenuates the behavioral parameters of
      dopaminergic supersensitivity when administered after abrupt haloperidol
      withdrawal. In the present study, the effects of GM1 and haloperidol co
      administration (5 mg/kg GM1 i.p. and 1 mg/kg haloperidol i.p., twice daily, for
      30 days) as well as the effects of a 3 day treatment with GM1 were investigated
      in rats withdrawn from haloperidol administration by measuring striatal D2
      dopamine receptor binding and dopamine turnover. The results showed that under
      these two experimental conditions GM1 modified neither the haloperidol-induced
      striatal D2 dopamine receptor up regulation nor the decrease in dopamine turnover
      produced by haloperidol withdrawal. These results suggest that the effects of GM1
      on behavioral supersensitivity are not related to modifications in dopamine
      receptor number or affinity and in the synaptic availability of this
      catecholamine.

PMID- 9519798
TI  - Neostigmine competitively inhibited nicotinic acetylcholine receptors in
      sympathetic neurons.
AB  - The present experiment investigates the effect of neostigmine on nicotinic
      acetylcholine receptors (nAChRs) in the cultured neurons from neonatal rat
      superior cervical ganglia (SCG). Using whole-cell patch clamp techniques, we
      found that the amplitudes of the currents induced by 50 microM
      dimethylphenylpiperazinium (DMPP) were 21.5+/-10.7%, 52.9+/-9.2% and 86.9+/-4.9%
      depressed at the increased concentrations of neostigmine 100, 200 and 400 microM,
      respectively. The inhibition of neostigmine decreased gradually with the
      increased concentration of nicotine from 10 to 160 microM. Lineweaver-Burk's
      double-reversible plot illustrated that neostigmine blocked neuronal nAChRs in a
      competitive manner. Hyperpolarization of membrane potential from -40 mV to -100
      mV did not significantly influence the blockade of neostigmine. Neostigmine could
      not accelerate the decay of the DMPP-induced currents, neither evoke any
      detectable currents in SCG neurons. The results indicate that neostigmine depress
      neuronal nAChRs in a competitive, concentration-dependent and voltage-independent
      manner, and can not facilitate desensitization of the receptors. The present data
      suggest that neostigmine blocks neuronal nAChRs by interacting with the ACh
      binding sites of the receptors.

PMID- 9519799
TI  - Characterization of muscarinic receptors mediating the contraction of the urinary
      detrusor muscle in cynomolgus monkeys and guinea pigs.
AB  - We have characterized in vitro the muscarinic receptors mediating the contraction
      of the detrusor muscle in Cynomolgus monkeys and guinea pigs using carbachol as
      the agonist and 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP, M3
      selective), methoctramine (M2-selective) and pirenzepine (M1-selective) as the
      antagonists. Carbachol induced a concentration-dependent contraction of the
      detrusor muscle of monkey and guinea pig yielding similar pD2 values of 6.67+/
      0.03 (n=50) and 6.77+/-0.06 (n=36), respectively. In the detrusor muscle of
      Cynomolgus monkey, all antagonists produced a concentration-dependent inhibition
      of carbachol-induced contractions, without decreasing the maximal response.
      Schild plot analysis yielded slopes not different from unity for all antagonists.
      The order of antagonist potency was: 4-DAMP (pA2=8.96)>pirenzepine
      (pA2=6.66)>methoctramine (pA2=6.03), suggesting that M3 receptors have a dominant
      role in mediating detrusor contraction. In the detrusor muscle of the guinea pig,
      4-DAMP and pirenzepine, but not methoctramine, produced a concentration-dependent
      inhibition of the carbachol-induced contractions, without decreasing the maximal
      response. Schild plot analysis yielded a slope not different from unity for 4
      DAMP and pirenzepine. 4-DAMP (pA2=9.07) had a higher potency than pirenzepine
      (pA2=6.66), a finding consistent with previously published data. The present
      study shows that in Cynomolgus monkey stimulation of the M3 subtype is dominant
      in mediating detrusor contraction upon carbachol stimulation.

PMID- 9519800
TI  - Possible direct effect of gonadotropin releasing hormone on human endometrium and
      decidua.
AB  - Decidualization of endometrial tissues, which is essential for implantation and
      the continuation of pregnancy, is induced by pituitary hormones that are
      regulated by gonadotropin releasing hormone (GnRH). Our objective was to
      determine the role of a direct action of GnRH on endometrial tissues by comparing
      the characteristics of receptors for GnRH in human endometrial and decidual
      tissues. Competitive binding studies were performed with the protease-resistant
      GnRH analogues, buserelin and [125I] buserelin. The effects of buserelin on
      phosphoinositol turnover were determined by the measurement of inositol 1,4,5
      triphosphate(IP3). The values for the dissociation constant (Kd) and number of
      binding sites (Bmax) per unit protein versus buserelin for endometrial tissues
      did not differ from the values for decidual tissues. However, the Bmax per unit
      DNA was significantly higher in endometrial tissues. Also, buserelin induced a
      significant increase in IP3 in decidual tissue. These results indicate that GnRH
      may be a potential modulator of the function in human endometrium and decidua.
      The signal transduction mechanism for GnRH action appeared to involve the
      accelerated turnover of phosphoinositol.

PMID- 9519801
TI  - Effect of serum on vascular smooth muscle function.
AB  - Serum contains many biologically active factors influencing cell growth and is
      commonly used as a culture medium supplement. It has not generally been
      appreciated that serum can affect vascular tone. We have observed that the
      contractile response of aortic rings previously exposed to 10% fetal bovine serum
      (FBS) for 24 hours and then stimulated with phenylephrine (0.01-1microM) or
      angiotensin II (1microM) is significantly diminished compared to 1) rings
      incubated in FBS for only 6 hours, 2) aortic rings previously incubated in 1% FBS
      or 3) aortic rings incubated in 10% bovine serum albumin for 24 hours. A similar
      attenuated response was also seen when the vascular aortic rings were incubated
      in heat inactivated adult bovine serum. To test whether prostaglandins might be
      induced by factors contained in serum and account for the diminished stimulated
      contractile response, rings were incubated for 24 hours in media containing 10%
      FBS with either indomethacin 10microM, corticosterone 100nM or 11
      dehydrocorticosterone 100nM. These agents are known to affect prostaglandin
      synthesis. Contractile responses were then measured accordingly. In each series,
      the previously attenuated contractile response to phenylephrine and to
      angiotensin II was fully restored with prostaglandin synthesis inhibition. Thus,
      factors contained in serum are capable of blunting the stimulated contractile
      response of rat aortic vessels. These serum factors appear to act by inducing
      prostaglandin synthesis in vascular tissue.

PMID- 9519802
TI  - Effect of anti-IL-4 and anti-IL-5 antibodies on allergic airway
      hyperresponsiveness in mice.
AB  - In order to study the role of IL-4 and IL-5 in allergen-induced airway
      hyperresponsiveness in mice, the effect of the combined administration of anti-IL
      4 and anti-IL-5 monoclonal antibodies (mAbs) on IgE response, airway inflammation
      and airway hyperresponsiveness was studied in sensitized Balb/c mice. Three
      inhalations of antigen caused an increase in the number of eosinophils in
      bronchoalveolar lavage fluid and in airway responsiveness to acetylcholine, with
      a significant elevation in the serum antigen-specific IgE level. Anti-IL-4 mAb
      inhibited IgE production but did not affect airway eosinophilia or
      hyperresponsiveness. Moreover, anti-IL-5 mAb inhibited airway eosinophilia but
      did not affect IgE production or airway hyperresponsiveness. The combined
      administration of anti-IL4 and anti-IL-5 mAbs, however, inhibited IgE antibody
      production, airway eosinophilia and hyperresponsiveness. These results suggest
      that inhibitory action of IL-4 and IL-5 in combination can effectively suppress
      the onset of antigen-induced airway hyperresponsiveness in mice.

PMID- 9519803
TI  - Endomorphin 1 and 2, endogenous mu-opioid agonists, decrease systemic arterial
      pressure in the rat.
AB  - The endogenous opioid peptides, endomorphin 1 and 2, are newly isolated, potent,
      and selective mu-opioid receptor agonists. In the present study, responses to
      endomorphin 1 and 2 were investigated in the systemic vascular bed of the rat.
      Endomorphin 1 and 2 induced dose-related decreases in systemic arterial pressure
      when injected in doses of 1-30 nmol/kg i.v. In terms of relative vasodepressor
      activity, endomorphin 1 and 2 were approximately equipotent with each other and
      with the ORL1 ligand, nociceptin (orphanin FQ), and were about 10-fold more
      potent than met-enkephalin in decreasing systemic arterial pressure.
      Vasodepressor responses to endomorphin 1 and 2 and met-enkephalin, but not to
      nociceptin, were inhibited by the opioid receptor antagonist, naloxone. These
      results demonstrate that endomorphin 1 and 2 produce significant naloxone
      sensitive decreases in systemic arterial pressure.

PMID- 9519804
TI  - Glucocorticoid regulation of adrenomedullin in a rat model of endotoxic shock.
AB  - Wistar rats were injected intravenously with bacterial lipopolysaccharide (LPS)
      and developed endotoxic shock with severe hypotension. This was accompanied by
      significantly elevated concentrations of adrenomedullin (AM) in the plasma and
      expression of high levels of AM mRNA in the lung. Pretreatment of the rats with
      dexamethasone (DEX) prevented hypotension caused by LPS administration, but
      plasma AM concentrations and AM mRNA levels in the lung remained elevated.
      Adrenalectomized (ADX) rats developed a more severe form of circulatory shock in
      response to a low-dose of LPS. This was accompanied by only a slight increase in
      circulating AM in the plasma. However, pretreatment of ADX rats with DEX caused
      substantial elevations of plasma AM concentrations and expression of AM mRNA in
      the lung. Our studies demonstrate that glucocorticoid upregulates the expression
      and secretion of AM in vivo, and endogenous glucocorticoid is required for
      increased AM secretion under certain conditions such as endotoxic shock.

PMID- 9519805
TI  - Effects of an endothelin ET(A)-receptor antagonist, S-0139, on cerebral vasospasm
      and behavioral changes in dogs intracisternally administered endothelin-1.
AB  - The effects of an endothelin ET(A)-receptor selective antagonist, S-0139, were
      examined using dogs given endothelin-1 (ET-1) into the subarachnoid space. ET-1
      at 40 pmol apparently constricted the basilar artery in anesthetized dogs and
      caused various grades of ataxia, facial clonus, nystagmus and other features in
      conscious dogs, partially mimicking those which have been reported for conscious
      rats. S-0139 could completely inhibit both the vasoconstriction and behavioral
      changes. It could also alleviate the behavioral changes caused by ET-1 in
      conscious dogs when given after the severe ataxia. We concluded that ET-1 in the
      subarachnoid space produces behavioral changes via endothelin ET(A)-receptor
      mediation similar to its cerebral vasoconstricting action, at least, in dogs.

PMID- 9519806
TI  - Characterization of a streptococcal antitumor glycoprotein (SAGP).
AB  - An acidic antitumor glycoprotein (SAGP) was purified from a crude extract of
      Streptococcus pyogenes, Su strain. Intraperitoneal injection with SAGP (20 mg
      protein/kg/day for 4 consecutive days) prolonged the life span of mice inoculated
      i.p. with Ehrlich ascite carcinoma cells and methylcholanthrene-induced
      fibrosarcoma cells (Meth A) up to 244% and 169% of that of the control mice,
      respectively. These in vivo antitumor effects were reduced in immunosuppressed
      mice. The effector spleen cells from the Meth A-inoculated and SAGP-injected mice
      showed a considerable cytostatic activity on Meth A cells in vitro, and
      immunosuppression studies suggested that carrageenan-sensitive and/or asialo-GM1
      positive spleen cells are responsible for the in vivo antitumor effect of SAGP.
      SAGP inhibited the cell growth of cultured cell lines including transformed
      hamster embryonic lung cells, murine leukemia L 1210, Meth A and human
      promyelocytic leukemia HL60 cells. The IC50s for the cell growth of these cells
      were all below 0.1 microg protein/ml. SAGP inhibited the incorporation of nucleic
      acid precursors into Meth A cells. It seems that sulfhydryl groups of the SAGP
      molecule are essential for the expression of the antitumor action of SAGP. The
      cell growth-inhibitory activity of SAGP was diminished in Meth A cells
      preincubated with pertussis toxin (IAP), whereas it was augmented in the cells
      preincubated with cholera toxin (CTX), suggesting the involvement of toxin
      sensitive GTP (G)-proteins in the SAGP-action. IAP and CTX-catalyzed ADP
      ribosylation assays confirmed that SAGP augmented the activity of IAP-sensitive G
      protein. In addition, this augmentation was detected neither in Meth A cells
      incubated with heat-inactivated SAGP nor in SAGP-insensitive L929 cells. SAGP
      induced apoptosis in Meth A and HL60 cells as assessed by DNA fragmentation. A
      single dose injection of SAGP (100 mg protein/kg, i.v., s.c., or i.p.) into mice
      produced no toxic signs except occasional pain responses observed for one week
      after the injection. Thus, SAGP is a low toxic substance that shows in vivo
      antitumor activity by modulating immune responses of the host, and also exhibits
      in vitro cell-growth inhibition through IAP-sensitive G-protein.

PMID- 9519807
TI  - HL-004, the ACAT inhibitor, prevents the progression of atherosclerosis in
      cholesterol-fed rabbits.
AB  - HL-004, N-(2,6-diisopropylphenyl) tetradecylthioacetamide, a novel acyl
      CoA:cholesterol acyltransferase (ACAT) inhibitor, was evaluated concerning the
      possible prevention of hyperlipidemia and atherosclerosis in 1% cholesterol-fed
      rabbits. HL-004 (0.2, 5 and 25 mg/kg) was orally administered once a day for 12
      weeks. HL-004 inhibited the rise of total serum cholesterol at a dose of 5 mg/kg
      and over. In the thoracic aorta, HL-004 at the doses of 5 mg/kg and 25 mg/kg
      reduced the total cholesterol content by 56.3% and 84.2% compared with control,
      and decreased ACAT activity, dose-dependently. HL-004 also attenuated the
      development of aortic lesions. The area of atherosclerotic lesions was reduced by
      30.3% with 5 mg/kg of HL-004 and 100% with 25 mg/kg. In this study, we suggest
      that the main reason for HL-004 preventing the progression of atherosclerosis is
      its hypocholesterolemic effect due to the inhibition of cholesterol absorption in
      the intestine.

PMID- 9519808
TI  - Hypotensive effect of gamma-glutamylmethylamide in spontaneously hypertensive
      rats.
AB  - The effect of gamma-glutamylmethylamide(GMA), one of the components of green tea
      extract, on the blood pressure in spontaneously hypertensive rats (SHR) was
      investigated. The effect of glutamic acid and r-glutamylethylamide (theanine),
      which is structurally similar to GMA, was also examined. When SHR were injected
      with glutamic acid (2000mg/kg), the blood pressure was not altered. The same dose
      of theanine decreased it significantly. GMA administration to SHR reduced the
      blood pressure significantly, and its degree of hypotensive action was more
      effective than that by theanine administration.

PMID- 9519809
TI  - A membrane protein associated with the prolactin receptor. Studies with a
      photoactivatable human growth hormone derivative.
AB  - Prolactin receptor from rat liver (PRL-R, 42 kDa) was cross-linked to a
      radiolabeled azidophenacyl derivative of human growth hormone ([125I]AP-hGH) to
      yield a 63 kDa adduct. In addition, a protein of Mr 50-52 K was detected as a 73
      kDa complex. Microsomes incubated with either (a) increasing amounts of [125I]AP
      hGH, or (b) a fixed amount of photoprobe and increasing concentrations of
      unlabeled hGH, showed that the 73/63 kDa band intensity ratio remains constant
      (0.71-0.77). Once transferred onto nitrocellulose membranes, only the 42 kDa
      protein is able to bind [125I]AP-hGH or [125I]hGH. Two anti-PRL-R monoclonal
      antibodies fail to cross-react with proteins of Mr 50-52 K. In membranes
      solubilized with 3-[(3-cholamidopropyl)-dimethylammonio]-1-propanesulfonate
      (CHAPS), a significantly lower amount of the 73 kDa complex is detected. Thus,
      the 50-52 kDa protein appears to be structurally unrelated to, but is presumably
      associated with the PRL-R. The 73 kDa complex is also detected under low membrane
      fluidity conditions (1 degree C), indicating that PRL-R associates to this 50-52
      kDa protein prior to hormone binding. Perfusion of rat liver with [125I]AP-hGH
      shows that this associated protein accompanies the receptor along its
      intracellular pathway.

PMID- 9519810
TI  - Protease inhibitors protect macrophages from lipopolysaccharide-induced
      cytotoxicity: possible role for NF-kappaB.
AB  - Recent studies suggest lipopolysaccharide (LPS) mediated cell death as underlying
      mechanism of hyporesponsiveness and dysfunction of macrophages in the late phase
      of septic shock. In the present study LPS (0.001 - 30 microg/ml) caused a
      concentration-dependent toxicity in the macrophage cell line (J774.1A) within 24
      h. The toxicity induced by LPS (1 microg/ml) was completely inhibited by the
      serine protease inhibitors, N-alpha-tosyl-L-phenylalanine chloromethyl ketone
      (TPCK) and N-alpha-tosyl-L-lysine chloromethyl ketone (TLCK) as measured by the
      mitochondrial-dependent oxidation of 3-(4,5-dimethyl-thiazol-2-yl)-2,5
      diphenyltetrazolium bromid (MTT) to formazan. These inhibitors antagonize the
      activation of nuclear transcription factor-kappaB (NF-kappaB) indirectly by
      inhibiting I kappaB alpha-protease. SN50, a direct inhibitor of NF-kappaB
      translocation into the nucleus also protected macrophages from LPS-mediated
      toxicity. We conclude from these data that the early phase signal transduction
      pathway leading to LPS-mediated cytotoxicity in macrophages involves the
      activation of NF-kappaB. Thus, I kappaB alpha-protease inhibitors might serve as
      therapeutical agents to maintain macrophage viability during sepsis and to
      prevent sepsis-induced immune dysfunction.

PMID- 9519811
TI  - Nicotine administration decreases the number of binding sites and mRNA of M1 and
      M2 muscarinic receptors in specific brain regions of rat neonates.
AB  - Nicotine has been shown to delay the developmental increase of muscarinic
      receptors in brain of rat neonates. In this study, we have examined the
      muscarinic receptor binding sites and corresponding messenger RNA in rat
      neonates, whose mothers received nicotine in the drinking water, using
      competition binding study and northern blot analysis. On postnatal 14th day,
      nicotine treatment led to a 61% reduction in the proportion of high-affinity
      sites for pirenzepine (M1-subtype) to total [3H]quinuclidinyl benzilate binding
      sites in cerebral cortex in rat neonate. Nicotine treatment also decreased that
      for 11-2[[2-[(diethylamino)methyl]-1-piperidinyl]-5,11-dihydro-6H-pyrido [2,3-b]
      [1,4] benzodiazepin-6-one (AF-DX 116) (M2-subtype) by 77% in cerebellum on
      postnatal 14th day. The levels of m1 and m2 muscarinic receptor messenger RNAs in
      the same brain regions were also decreased in the same day after nicotine
      treatment. On postnatal 35th day, no difference was observed in binding sites or
      in messenger RNA levels of the brain regions tested (cerebral cortex, midbrain,
      hippocampus, cerebellum and brainstem). Our results show that nicotine reduces
      muscarinic receptor subtypes in developing rat brain, in part, through
      suppression of the messenger RNA expression, but that the effects are different
      among brain regions and subtypes.

PMID- 9519812
TI  - Evaluation of the age-dependent development of lymphocyte surface receptors in
      children.
AB  - Components and functions of the immune system change during postnatal
      development, not only in the first years of life, but well through adolescence
      and even into adult life. These age-dependent changes within the immune system
      greatly complicate any attempt to assess pathological alterations of immunologic
      variables in children. The need for studies on possible substance-induced
      changes, including risk assessment of environmental chemicals, has increased the
      necessity to establish reference ranges for certain immunologic variables against
      which an abnormal developmental status can be evaluated. In the present study age
      related changes of surface receptors on peripheral white blood cells were studied
      in 82 children, aged between 2 months and 17 years. The blood samples were triple
      labeled with monoclonal antibodies followed by a whole blood lysis technique and
      were subsequently analyzed by flow cytometry. Complex statistical analyses were
      performed in order to determine probability ranges for some immunological
      variables. In this paper we describe the age-dependent development of components
      involved in major maturational processes, including the appearance and varying
      expression of adhesion receptors (CD11a, CD18, CD28, CD29, CD44, CD49d and CD54)
      on CD4+ "helper" cells and CD8+ "suppressor and cytotoxic" cells. A clear-cut
      increase of high epitope density expression of the integrins on both CD4+ and
      CD8+ cells was noted. These results suggest that the components of immune T cells
      for performing adhesion by interacting with other cells and many matrix
      components are largely acquired during postnatal development. Maximal levels of
      adhesion receptor expression are reached at different ages depending on the
      specific T cell subpopulation.

PMID- 9519813
TI  - Regional sympathetic activity in pre-hypertensive phase of spontaneously
      hypertensive rats.
AB  - Imbalances in central and peripheral sympathetic nervous system (SNS) activity
      have been observed in essential and experimental hypertension. This study was
      carried out in order to evaluate SNS activity in two distinct tissue types of
      spontaneously hypertensive rats (SHR), compared to Wistar-Kyoto normotensive
      (WKY) rats, in the pre-hypertensive phase (4-5 weeks of age). Interstitial
      concentrations of norepinephrine (NE) and other catecholamines were measured by
      microdialysis in striated muscle, whose tone is controlled by baroreflexes, and
      in the subcutaneous adipose tissue where sympathetic output mainly controls
      metabolism. Two groups of SHR and WKY male rats were studied, aged 4-5 weeks,
      with a mean body weight of 92 and 86 g respectively. Systolic blood pressure
      (SBP, tail-cuff) values were 113 mm Hg (SD +/- 6.2) in SHR and 108 mm Hg (SD +/-
      7.3) in WKY rats (p=0.28,t test). Two microdialysis probes were positioned in the
      subcutaneous fatty tissue and in the striated muscle of the parascapular region
      and perfused with Ringers' solution. The dialysate was collected every thirty
      minutes for 3 hours and analyzed in HPLC-ED to determine the content of NE and
      other catecholamines. Interstitial levels of NE were higher in SH than in WKY
      rats in both tissues. Mean NE values from subcutaneous adipose tissue in 4-5 week
      old SHR were 1162 +/- 193 pg/ml compared to 496 + 188 pg/ml in WKY rats (p<0.001,
      t test). Muscle tissue NE levels in SHR were 1241 +/- 337 pg/ml vs. 521 +/- 138
      pg/ml in WKY rats (p<0.001, t test). Plasma NE concentrations (279 +/- 61 pg/ml
      in SHR vs 246 + 69 pg/ml in WKY P = 0.65, t test) were not significantly
      different between the two strains at this young age. These findings suggest SNS
      hyperactivity in young SHR, though still normotensive, possibly dissociated from
      regional components of regulation (baroreceptor control in striated muscle and
      metabolic control in subcutaneous adipose tissue).

PMID- 9519814
TI  - Evidence of non-synaptic regulation of postpartum uterine contractility in the
      rat.
AB  - Myometrial tissue rings from postpartum rats (24 h after delivery) were studied
      in vitro by electric field stimulation, and the alpha1/beta2-adrenoceptor ratio
      was determined by a radioligand binding technique. Pregnancy-denervated uterine
      rings were stimulated by long-duration pulses (100 ms). The contractions were
      inhibited by beta2-agonists (terbutaline and fenoterol) and alpha-antagonists
      (phentolamine, urapidil and yohimbine) in a concentration-dependent manner. Their
      effects were not altered by the adrenergic neuron-blocking agent bretylium. The
      alpha-antagonists (except phentolamine) elicited the same maximal inhibition as
      the beta2-agonists. Receptor assays revealed that the alpha1/beta2 ratio was
      about 2 in the measured uteri. It was concluded that the inhibitory effects of
      alpha-antagonists and beta2-agonists are mediated via non-synaptic adrenoceptors
      of the denervated postpartum rat uterus. The same inhibitory activity could be
      explained by the greater amount of alpha-receptors. It is believed that this is
      the first functional proof of the existence of non-synaptic alpha1-adrenoceptors
      in smooth muscle.

PMID- 9519815
TI  - Distinct interleukin-1beta-converting enzyme family proteases mediate cisplatin-
      and staurosporine-induced apoptosis of mouse proximal tubule cells.
AB  - Interleukin-1beta converting enzyme (ICE) family proteases (caspases) are known
      to be implicated as important effectors of apoptotic pathways. The purpose of
      this study was to elucidate the role of ICE family proteases in apoptosis of
      mouse cells derived from the terminal proximal tubule (S3) treated with
      cisplatin, an anti-tumor drug, or staurosporine, a protein kinase C inhibitor.
      For this purpose, we measured the activities of ICE family proteases and examined
      the effects of tetrapeptide and viral ICE family protease inhibitors on the
      activities of ICE family proteases in and the degree of apoptosis of S3 cells
      treated with cisplatin and staurosporine. RT-PCR analysis revealed that S3 cells
      as well as mouse kidney express mRNA for ICE and CPP32, an ICE family protease.
      Results of enzymatic analysis, determination the degree of DNA fragmentation and
      cytotoxicity test suggest that CPP32 mediates cisplatin-induced apoptosis of S3
      cells, whereas ICE family proteases other than CPP32 mediate staurosporine
      induced apoptosis of S3 cells. In conclusion, distinct ICE family proteases
      mediate apoptosis of mouse proximal tubule cells depending on the stimuli to
      which the cells are exposed.

PMID- 9519817
TI  - Influence of dosing time on pharmacological action of G-CSF in mice.
AB  - The role of the susceptibility of living organisms and the pharmacokinetics of G
      CSF on the rhythm of granulocyte colony-stimulating factor (G-CSF) activity was
      investigated. ICR male mice were housed in a standardized light-dark cycle
      (lights on at 0700, off at 1900) with food and water ad libitum. The leukocyte
      counts at 2 and 24 hr after G-CSF (250 microg/kg, i.v.) injection were
      significantly higher in mice injected with the drug at 0700 than at 1900 (p<0.01,
      respectively). The higher leukocyte-increasing effect corresponded to drug dosing
      at the time in which the granulocyte colony formation stimulated by G-CSF and DNA
      synthesis increased and the lower effect corresponded to drug dosing at the time
      in which they decreased. The rhythmicity corresponded to that in plasma G-CSF
      concentration. The present study suggests that the rhythm of G-CSF activity is
      caused by that of the sensitivity of bone marrow cells to the drug and the
      pharmacokinetics of the drug.

PMID- 9519816
TI  - Overexpression of manganese-superoxide dismutase prevents methylmercury toxicity
      in HeLa cells.
AB  - HeLa cells were stably transformed with plasmid constructs that allowed
      constitutive expression of antioxidant enzymes such as catalase, glutathione
      peroxidase (GSH-Px), Cu,Zn-superoxide dismutase (Cu,Zn-SOD) or Mn-superoxide
      dismutase (Mn-SOD) to examine the involvement of reactive oxygen generation in
      methylmercury toxicity. Overexpression of catalase, GSH-Px or Cu,Zn-SOD did not
      affect the sensitivity of HeLa cells against methylmercury. However, the
      sensitivity of HeLa cells against methylmercury was decreased by overexpression
      of Mn-SOD, an enzyme localized in matrix of mitochondria and which decomposes
      superoxide anions. These results suggest that formation of superoxide anions in
      the mitochondria might be involved in the mechanism of the cytotoxicity of
      methylmercury.

PMID- 9519818
TI  - Cytotoxic T lymphocytes in AIDS pathogenesis: lessons to be learned from the
      macaque model of simian immunodeficiency virus infection.

PMID- 9519819
TI  - Evaluation of a candidate human immunodeficiency virus type 1 (HIV-1) vaccine in
      macaques: effect of vaccination with HIV-1 gp120 on subsequent challenge with
      heterologous simian immunodeficiency virus-HIV-1 chimeric virus.
AB  - Human immunodeficiency virus type 1 (HIV-1) envelope vaccines can now be
      evaluated for efficacy in macaques by challenging with chimeric viruses in which
      the env, tat and rev genes of simian immunodeficiency virus (SIV) have been
      replaced by those of HIV-1. Most experiments have so far been conducted using
      gp120 molecules derived from T-cell-adapted LAI or MN strains of HIV-1, which
      predominantly use the CXCR-4 co-receptor. These vaccines protect against
      infection by apathogenic chimeric virus carrying the same envelope sequences. In
      the experiment described here, four macaques were vaccinated with W61D gp120
      derived from a low passage Dutch isolate and capable of inhibiting the binding of
      MIP1beta to the co-receptor CCR-5. This vaccine was potent, inducing high titres
      of binding and neutralizing antibodies against the homologous HIV-1 and tenfold
      lower titres against a heterologous challenge virus (SHIV(SF33)) in which the
      env, tat and rev genes of SIV had been replaced by those of a San Francisco
      isolate, HIV-1(SF33). Despite strong immune responses to the vaccine there was no
      evidence that it protected against challenge with this chimeric virus. The
      antigenic divergence between vaccine and challenge virus or the increased
      virulence of the challenge virus may be responsible for the inability of this
      vaccine to protect against infection by SHIV(SF33).

PMID- 9519820
TI  - Infection with foot-and-mouth disease virus results in a rapid reduction of MHC
      class I surface expression.
AB  - The modulation of MHC class I molecule expression on the surface of cells as a
      consequence of foot-and-mouth disease virus (FMDV) infection has been examined.
      On cells infected with FMDV, class I expression was reduced to approximately 70%
      of the initial value 3 h after the infection and to 53% after 6 h. On cells
      depleted of surface class I complexes by acid treatment, the appearance of newly
      assembled class I-peptide complexes on the cell surface of non-infected cells
      increased immediately upon neutralization and original class I levels were
      recovered in about 20 h. In contrast, the appearance of new peptide-bound class I
      molecules on the cell surface was inhibited as early as 30 min after FMDV
      infection. Since the shut-down of FMDV-mediated host protein synthesis occurs
      approximately 2-3 h post-infection, this result suggests that an earlier event,
      which prevents the surface expression of newly synthesized complexes, is induced
      following FMDV infection. Thus, FMDV-infected cells rapidly become unable to
      present viral peptides in association with MHC class I molecules to T
      lymphocytes. Such a mechanism would assist virus evasion of the cytotoxic immune
      response of the host.

PMID- 9519821
TI  - Identification of a major determinant of mouse neurovirulence of dengue virus
      type 2 using stably cloned genomic-length cDNA.
AB  - A genomic-length cDNA clone corresponding to the RNA of dengue virus type 2 (DEN
      2) New Guinea C strain (NGC) was constructed in a low copy number vector. The
      cloned cDNA was stably propagated in Escherichia coil and designated pDVWS501.
      RNA transcripts produced in vitro from the cDNA using T7 RNA polymerase yielded
      infectious virus (MON501) upon electroporation into BHK-21 cells. When compared
      with parental NGC virus, MON501 replicated to similar levels in Aedes albopictus
      C6/36 cells and showed similar neurovirulence in suckling mice. In contrast, a
      second genomic-length cDNA clone (pDVWS310) used as an intermediate in the
      construction of pDVWS501 produced virus (MON310) that replicated well in C6/36
      cells but was not neurovirulent in mice. MON310 contained the prM and E genes of
      the non-neurovirulent PUO-218 strain in an NGC background. There were seven amino
      acid differences between the prM and E proteins of MON310 and MON501. The
      differences were generally conservative, with the exception of E residue 126,
      which was Glu in MON310 and Lys in MON501. To examine the role of this residue in
      mouse neurovirulence, substitutions of Glu --> Lys and Lys --> Glu were made in
      MON310 and MON501, respectively. The properties of these mutants clearly
      demonstrated that Lys at E residue 126 is a major determinant of DEN-2 mouse
      neurovirulence.

PMID- 9519822
TI  - The sequence and phylogenetic analysis of a novel hepatitis E virus isolated from
      a patient with acute hepatitis reported in the United States.
AB  - A variant of hepatitis E virus (HEV), designated HEV US-1, was identified in a
      hepatitis patient in the United States (US); the patient had no history of travel
      to areas where HEV is endemic. Nucleotide sequences were obtained from the 5' end
      of open reading frame (ORF) 1 (1418 nt), the 3' end of ORF1 (1359 nt), the entire
      ORF2 and ORF3 regions, and the 3'-untranslated region (2127 nt). The HEV US-1
      strain is significantly divergent from other human HEV isolates with nucleotide
      identities ranging from 76.8 to 77.5%. Phylogenetic analyses indicate that HEV US
      1 and a recently discovered HEV variant from swine may represent separate
      isolates of a new strain of HEV, significantly divergent from the Mexican and
      Burmese strains. Synthetic peptides derived from the carboxyl amino acids of ORF2
      and ORF3 were shown to be useful for detecting exposure to HEV. In addition, IgM
      class antibodies directed against HEV US-1 synthetic peptides were detected in
      the US patient infected with HEV US-1, but were absent using synthetic peptides
      from the Burmese or Mexican strains of HEV. A preferential reactivity to HEV US-1
      specific peptides has lead to the identification of a second isolate of this
      virus also from a patient with acute hepatitis from the US. The discovery of
      these HEV variants may be important in understanding the worldwide distribution
      of HEV infection.

PMID- 9519823
TI  - The Thogoto orthomyxovirus cRNA promoter functions as a panhandle but does not
      stimulate cap snatching in vitro.
AB  - The cRNA promoter of Thogoto virus, a tick-borne orthomyxovirus, was investigated
      using an in vitro polymerase assay based on purified viral cores and synthetic
      oligoribonucleotides corresponding to the 3' and 5' ends of cRNA. In vitro
      polymerase activity relied on an interaction between the 3' and 5' ends of cRNA
      and was ApG primer-dependent. Mutational analysis of the promoter showed that
      interstrand base-pairing of residues 11 and 12 of the 3' promoter arm with
      residues 10 and 11 of the 5' promoter arm, respectively, was essential for
      polymerase activity. These data provide the first clear evidence for a cRNA
      panhandle in an orthomyxovirus. No evidence was obtained for the presence of a 5'
      or 3' hook structure in the cRNA promoter, and transcription could not be primed
      with rabbit globin mRNA or synthetic cap analogues. This demonstrates that cap
      snatching activity relies on the presence of the vRNA terminal sequences.

PMID- 9519824
TI  - Monoclonal anti-idiotypic antibodies mimicking the immunodominant epitope of
      influenza virus haemagglutinin elicit biologically significant immune responses.
AB  - The MAb IIB4 recognizes an immunodominant epitope on influenza virus
      haemagglutinin (HA) which is shared by different strains of the human subtype H3.
      This epitope includes amino acids 198, 199 and 201, as determined by selection of
      IIB4 escape mutants, and is involved in haemagglutination-inhibition (HI) and
      virus-neutralization (VN). We have developed anti-idiotypic MAbs (Ab2) that mimic
      the IIB4 epitope. Two Ab2, 78 and 464, completely inhibited binding of MAb IIB4
      to the virus. Nucleotide sequences of VL- and VH-encoding regions were determined
      for IIB4 and both Ab2. VH of IIB4 and 78 belong to the same IgG family (VII) and
      show high nucleotide identity (89%). Conversely, VH and VL sequences of both
      internal image-bearing Ab2 revealed lower degrees of identity (61 and 50%,
      respectively). Ab2 were used for syngeneic immunization to elicit polyclonal Ab3
      responses. Like Ab1, Ab3 immunoprecipitated viral HA and displayed HI and VN
      activity. The different VN activity of anti-78 and anti-464 in vitro correlated
      with the affinities of their corresponding Ab2 to IIB4. In vivo immunization with
      either Ab2 protected 15-37% of mice against lethal influenza infection or delayed
      dying. In contrast to VN activity of Ab3 in vitro, there was no significant
      difference between the protection of mice induced by Ab2 78 and 464. We
      demonstrate, for the influenza model, that active immunization with a single
      influenza virus HA epitope in the form of its internal image leads to partial
      protection in vivo.

PMID- 9519825
TI  - The PA influenza virus polymerase subunit is a phosphorylated protein.
AB  - The induction of proteolysis by expression of the influenza virus PA polymerase
      subunit is the only biochemical activity ascribed to this protein. In the course
      of studying viral protein synthesis by two-dimensional gel electrophoresis, we
      observed the existence of several PA isoforms with different isoelectric points.
      These isoforms were also present when the PA gene was singly expressed in three
      different expression systems, indicating that a cellular activity is responsible
      for its post-translational modification. In vivo labelling with
      [32P]orthophosphate, followed by two-dimensional gel electrophoresis, clearly
      demonstrated the incorporation of phosphate into the PA molecule. Phosphoserine
      and phosphothreonine epitopes were present in PA, while phosphotyrosine residues
      were absent, as tested by immunoblotting with specific antibodies. These facts,
      as well as the presence of multiple consensus sites for casein kinase II (CKII)
      phosphorylation, prompted us to test the involvement of this kinase in PA
      covalent modification. PA protein purified by immunoprecipitation could be
      specifically labelled by the catalytic alpha subunit of human CKII, which was
      expressed and purified from bacteria. Collectively, these data demonstrate that
      the PA subunit of the influenza virus RNA polymerase is a phosphoprotein.

PMID- 9519827
TI  - Characterization of the interactions of human papillomavirus type 16 E6 with p53
      and E6-associated protein in insect and human cells.
AB  - Human papillomavirus (HPV) 16 E6 induces the degradation of the tumour suppressor
      protein p53 by the ubiquitin-dependent proteolysis pathway. In vitro, this
      process involves the formation of a trimolecular complex between E6, p53 and a
      cellular protein E6-associated protein (E6-AP). However, an analysis of their
      potential interactions in vivo has not been carried out. We have established a
      model for the expression and analysis of the interactions of these three proteins
      in insect cells, a eukaryotic system where potentially crucial modifications of
      the proteins will occur. In baculovirus-infected cells the degradation of p53 can
      occur. However, p53 is only degraded early in the infectious cycle due to a lack
      of ATP at later times. Consequently, substantial quantities of material can be
      produced in this system for further analysis. Evidence is also provided that, in
      vivo, E6 can interact with p53 in the absence of E6-AP and that E6-AP can
      interact with p53 in the absence of E6. Furthermore, analysis of the subcellular
      localization of the proteins using both biochemical fractionation and indirect
      immunofluorescence suggests that the degradation of p53 occurs in the perinuclear
      region of the cell.

PMID- 9519826
TI  - Monoclonal antibody neutralization escape mutants of respiratory syncytial virus
      with unique alterations in the attachment (G) protein.
AB  - Five monoclonal antibody (MAb) neutralization escape mutants of respiratory
      syncytial virus (RSV) were produced by growing the Long strain RSV (group A
      virus) in the presence of a neutralizing, group cross-reactive MAb specific for
      the attachment protein (G). Four viruses (RSV-2, -6, -14 and -15) had amino acid
      replacements clustered within a highly conserved centrally located 13 amino acid
      region (position 164-176). Reactivity with group A-specific MAbs and with
      polyclonal anti-G serum was maintained and growth kinetics were unaffected. An
      additional virus (RSV-3) had four amino acid substitutions in the cytoplasmic
      tail and transmembrane region of G, and had restricted growth and formed small
      syncytia. Immunofluorescent and Western blot analysis indicated that G protein
      was not membrane associated and had reduced incorporation into the virion,
      thereby escaping neutralization by L9 and polyclonal anti-G serum. The
      predominant form of G produced by RSV-3 was found in infected cell supernatants,
      consistent with the size of secreted G.

PMID- 9519828
TI  - Epithelial specific transcriptional regulation of the bovine papillomavirus 4
      promoter by E2.
AB  - Bovine papillomavirus 4 (BPV-4) is a mucosal epitheliotropic papillomavirus. It
      encodes a transcriptional regulator, E2, which acts on the BPV-4 transcriptional
      control region (the long control region or LCR) to regulate transcription. The
      distribution of E2 binding sites within the LCR of BPV-4 is identical to that of
      the human papillomaviruses HPV-16 and HPV-18, indicating that the mechanism of
      transcriptional control by E2 of mucosal epitheliotropic papillomaviruses is
      conserved. In this study it has been shown that E2 activates transcription
      through the BPV-4 LCR promoter in primary bovine palate keratinocytes but not in
      primary bovine palate fibroblasts. The epithelial specific transcriptional
      activation of the BPV-4 LCR by E2 is promoter-specific because following binding
      to the BPV-4 LCR placed in an enhancer mode, E2 can activate transcription from
      heterologous promoters, such as SV40, in both keratinocytes and fibroblasts.
      Chimaeric VP16-E2 molecules suggest that the epithelial specific transcriptional
      activation of the BPV-4 LCR promoter is mediated by the E2 transactivation
      domain. Although low to intermediate levels of E2 can activate transcription from
      the BPV-4 LCR promoter, high levels of E2 result in down-regulation of
      transcription from this promoter in keratinocytes. Mutation of E2 binding site 1
      (BS1), which is 3 bp upstream from the TATA box, abrogates down-regulation of
      transcription by high levels of E2. The results present a model system for
      studying transcriptional regulation of mucosal epitheliotropic papillomavirus
      LCRs by E2.

PMID- 9519829
TI  - Ovine adenovirus (OAV287) lacks a virus-associated RNA gene.
AB  - Ovine adenovirus OAV287 (OAV) is the prototype of a virus group which is
      phylogenetically distinct from the mastadenoviruses and aviadenoviruses. The
      genome arrangement of OAV showed that virus-associated (VA) RNA genes were not
      located between the reading frames for p52/55K and terminal protein as these
      overlapped. To determine whether VA genes were located elsewhere, several
      approaches were used. Nuclear extracts containing RNA polymerase III activity
      were used to transcribe OAV genome fragments in vitro. A product of approximately
      120 bp was produced from two widely separated coding regions of the genome.
      However, when these were subcloned and used as radiolabelled probes to analyse
      RNA from OAV-infected cells, no VA-like RNA was detected, although late mRNAs
      that were transcribed from the regions were identified. In addition, 5'
      radiolabelling of small RNA species in control- and OAV-infected cells followed
      by gel analysis did not identify candidate VA RNAs. Radiolabelling of proteins in
      control- and OAV-infected cells showed that there was little preferential
      translation of viral proteins compared with host polypeptides, in contrast to the
      situation for adenovirus 5 (Ad5). In addition, the kinetics of OAV infection were
      slower than observed for human adenoviruses. Collectively, the data suggest that
      OAV is unique in that it does not produce VA RNA during infection. This
      conclusion is supported by a comparison of the genomes of the phylogenetically
      related OAV and egg drop syndrome viruses which shows that the VA gene identified
      in the latter is located in a region absent from OAV.

PMID- 9519830
TI  - Role of the DR2 repeat array in the regulation of the ICP34.5 gene promoter of
      herpes simplex virus type 1 during productive infection.
AB  - Previous analyses using transient transfection assays indicated that the promoter
      for the gene encoding the herpes simplex virus type 1 (HSV-1) neurovirulence
      protein ICP34.5 can be divided into an essential core region of approximately 80
      bp and two potent upstream silencer domains corresponding to the DR2 and DR6
      repeat arrays. In order to examine the potential role of transcriptional
      silencing during productive HSV-1 infection, recombinant viruses were generated
      in which wild-type or mutant ICP34.5 promoters controlling the expression of a
      chloramphenicol acetyltransferase reporter gene were inserted into the thymidine
      kinase gene of the viral genome. The intact promoter in the virus HSV-delta1CAT
      exhibited delayed-early kinetics of expression that were comparable to those of
      the ICP34.5 gene promoter at its native site in the genome. Deletion of the core
      promoter domain eliminated promoter activity in the virus HSV-delta5CAT,
      indicating that this region was required for expression not only in transient
      transfections assays but also in the context of the viral genome. However,
      deletion of the DR2 repeat array from the ICP34.5 promoter in the virus HSV
      delta7CAT was found to increase promoter activity only minimally at late times,
      and even to reduce activity at early times. Thus, in marked contrast to its
      behaviour in transient expression assays, the DR2 repeat array does not appear to
      act as a transcriptional silencer in the context of the HSV-1 genome during
      productive infection.

PMID- 9519831
TI  - A neuroattenuated ICP34.5-deficient herpes simplex virus type 1 replicates in
      ependymal cells of the murine central nervous system.
AB  - Herpes simplex virus type 1 (HSV-1) variant 1716 is deleted in the gene encoding
      ICP34.5 and is neuroattenuated after intracranial inoculation of mice. Although
      the mechanism of attenuation is unclear, this property has been exploited to
      eliminate experimental brain tumours. Previously, it was shown that infectious
      1716 was recoverable for up to 3 days after intracranial inoculation suggesting
      that there may be limited replication in the central nervous system (CNS). Here
      it is demonstrated that 1716 replicates in specific cell types (predominantly CNS
      ependymal cells) of BALB/c mice, using immunohistochemical, immunofluorescence,
      in situ hybridization and virus titration studies. While 1716-infected mice
      exhibited no overt signs of encephalitis, histological analysis showed a
      persistent loss of the ependymal lining. Thus, although ICP34.5-deficient viruses
      are neuroattenuated, they do retain the ability to replicate in and destroy the
      ependyma of the murine CNS. A detailed understanding of the mechanism(s) of
      neuroattenuation and limited replication could lead to the rational design of
      safe HSV vectors for cancer and gene therapy in the CNS.

PMID- 9519832
TI  - Examination of determinants for intranuclear localization and transactivation
      within the RING finger of herpes simplex virus type 1 IE110k protein.
AB  - The herpesvirus regulatory protein IE110k possesses a cysteine-rich, RING finger
      motif required for its role in transactivation and virus replication. IE110k also
      localizes to subnuclear compartments termed PODs (PML oncogenic domains).
      Localization to PODs induces redistribution of the proteins associated with this
      nuclear compartment, including the cellular RING finger protein, PML. Here we
      construct a series of deletions, RING domain swaps and point mutations to analyse
      specific requirements within the IE110k RING finger for subnuclear localization,
      redistribution of PML and transactivation and we examine the relationship between
      these activities. We find that IE110k localizes to distinct nuclear subdomains
      that are more numerous than the cellular PODs and that mutation of two residues
      within a predicted loop of the RING finger, or replacing the IE110k RING finger
      with a RING finger from a cellular gene abrogates the ability of IE110k to
      localize to these extra compartments and traps IE110k in the original PODs. We
      further demonstrate that RING fingers from the cellular genes mdm-2 and Bmi I,
      when placed within IE110k, alter the nuclear distribution of IE110k, do not
      transactivate, and do not redistribute PML. We also demonstrate that the majority
      of wild-type IE110k, like PML, is associated with the nuclear matrix. Although
      substitutions and deletions within the RING finger abolish transactivation, these
      mutant proteins remain tightly associated with the matrix. These results further
      dissect the determinants involved in different aspects of nuclear
      compartmentalization of IE110k and are discussed in relation to PML, PODs and the
      IE110k RING finger.

PMID- 9519834
TI  - Precipitous clearance of herpes simplex virus antigens from the peripheral
      nervous systems of experimentally infected C57BL/10 mice.
AB  - Clearance of herpes simplex virus (HSV) from spinal ganglia of experimentally
      infected mice is known to be dependent on CD8+ T-cells but not on destruction of
      infected neurons, consistent with a non-cytolytic Tc2 response in the peripheral
      nervous system. Here, we demonstrate the striking rapidity of such a response in
      C57BL/10 mice. The number of neurons containing viral DNA and viral antigens
      increased until 136 h after inoculation of virulent HSV type 1 (strain SC16) into
      flank skin. Subsequent disappearance of HSV DNA and antigens from infected
      ganglia was virtually complete only 8 h later. A consistent and unexpected
      observation was detection of viral antigens in sensory nerve axons for at least 8
      h after their disappearance from neuronal somas, raising the intriguing
      possibility that virus or viral proteins may be transported distally after
      infection has been terminated.

PMID- 9519833
TI  - Viral and cellular requirements for entry of herpes simplex virus type 1 into
      primary neuronal cells.
AB  - Herpes simplex virus (HSV) causes many disease states including mucosal lesions,
      encephalitis or disseminated infection in the immunocompromised host. These
      diverse clinical manifestations reflect the capacity of the virus to infect both
      epithelial and neuronal cell types. Determining the requirements for virus entry
      into both cell types may provide insights into the pathogenesis of HSV. Previous
      studies have focused on identifying viral and cellular requirements for entry
      using epithelial cells. However, little is known about the requirements for
      binding and entry into neuronal cells. The purpose of the studies reported here
      was to identify viral and cellular components involved in entry of HSV-1 into
      primary neuronal cells. Heparan sulfate glycosaminoglycans were found to serve as
      a receptor for entry of HSV-1 into primary neuronal cells. Evidence to support
      this includes the findings that heparin (an analogue of heparan sulfate)
      competitively inhibited virus binding and expression of immediate early virus
      gene products. In addition, heparitinase removed viral receptors and inhibited
      virus entry. In epithelial cells, deletion of HSV-1 glycoprotein C (gC) results
      in virions that have reduced specific binding activity (virus particles bound per
      cell) and specific infectivity. However, in neuronal cells, it was found that
      deletion of gC resulted in no loss in specific binding activity, but did result
      in significant impairment of virus entry as measured by expression of immediate
      early viral gene product. Taken together, these findings suggest cell-type
      differences in virus binding and entry and a different role for gC in neuronal
      cell infection.

PMID- 9519835
TI  - The BglII-N fragment of herpes simplex virus type 2 contains a region responsible
      for resistance to antiviral effects of interferon.
AB  - Double infection with two interferon (IFN)-sensitive strains of herpes simplex
      virus (HSV), HSV-1(17syn) and HSV-2(UW268), showed reduced inhibition of virus
      growth by IFN. Intertypic recombinants with IFN resistance were obtained from the
      doubly infected cultures. These results indicate that HSV IFN resistance is
      controlled by at least two genetic regions. Restriction endonuclease analysis
      demonstrated that the recombinants were similar to HSV-2 in their genomic
      structure but the BamHI-A, BglII-I and BglII-N fragments of HSV-2 were commonly
      lost in the recombinants, suggesting that any of these fragments could be
      associated with HSV-2 IFN resistance. We cloned these fragments and BamHI-E,
      which overlaps BglII-N, from an IFN-resistant HSV-2 strain, HSV-2(G), and
      examined each fragment for its ability to rescue IFN resistance of HSV-2(UW268)
      by co-transfecting with the HSV-2(UW268) genome. Of the HSV-2(G) fragments, only
      BglII-N increased plating efficiency of progeny viruses in IFN-treated cells. An
      IFN-resistant HSV-2 clone was obtained from the BglII-N of HSV-2(G) and HSV
      2(UW268) genome co-transfected culture, and a part of BglII-N of HSV-2(UW268) was
      replaced with that of HSV-2(G) in the HSV-2 clone. Thus, it was concluded that
      one of the HSV regions encoding IFN resistance is located on the BglII-N fragment
      of HSV-2.

PMID- 9519836
TI  - Persistence of parvovirus B19 DNA in testis of patients with testicular germ cell
      tumours.
AB  - Germ cell tumours (GCT) of the testis are the most common malignant tumours
      occurring in young adults. In view of the young age of patients, the increasing
      incidence of GCT and the overexpression of wild-type p53 observed in a majority
      of tumours, the possibility of the involvement of a virus in the development of
      this cancer was considered. Testicular GCT were analysed for the presence of
      cytomegalovirus and Epstein-Barr virus (EBV), which are known to cause
      overexpression of wild-type p53 protein, and parvovirus B19. The testicular
      tissue of 39 patients with testicular GCT and 12 patients with healthy testicular
      tissues was tested for presence of viral DNA by PCR. Neither cytomegalovirus nor
      EBV DNAs were detected in the 39 tumours analysed, but parvovirus B19 DNA
      sequences were demonstrated in the testicular tissue of 85% (33/39 cases) of
      patients with GCT. The sera of 16 of the 39 patients with GCT were tested for the
      presence of parvovirus B19 IgM and IgG. B19-specific IgG was detected in the sera
      of 11 patients (69%). Only one case was positive for parvovirus B19 IgM, which
      was also shown to have B19 genome sequences in the serum by PCR, indicating that
      in a majority of cases an acute B19 infection can be excluded as being the source
      of the B19 DNA sequences in the testis. B19 DNA could not be detected in normal
      testicular tissue and thus parvovirus B19 could play a role, direct or indirect,
      in the development of testicular GCT or have tropism for the tumour cells.

PMID- 9519837
TI  - Two segments in the genome of the immunosuppressive minute virus of mice
      determine the host-cell specificity, control viral DNA replication and affect
      viral RNA metabolism.
AB  - Two strains of minute virus of mice (MVM) show different host-cell specificities.
      MVM(i) grows in T lymphocytes whereas MVM(p) is fibroblast-specific. By
      constructing recombinant viral DNAs between the genomes of the two strains, we
      have shown that two segments of the MVM(i) genome are required for lytic viral
      growth in T lymphocytic EL4 cells. One segment (iE) was found between nucleotides
      1084 and 2070, in a region encoding the early viral proteins and containing mRNA
      splice signals and the late P39 promoter. The other (iL) was between nucleotides
      3523 and 4339 in the region coding for capsid protein. The P39 promoters within
      the E segment from MVM(i) or MVM(p) were equally active in transfected EL4 cells.
      However, pE-containing MVM DNA produced more NS2 mRNA than iE-containing DNA,
      apparently the result of virus-strain-specific differences in the regulation of
      splicing.

PMID- 9519838
TI  - Proline-138 is essential for the assembly of hepatitis B virus core protein.
AB  - In small RNA viruses, arm-like segments located at the N or C termini have been
      suggested as mediators in the assembly of the capsid proteins. In many cases the
      arms of several subunits converge at a common point (the symmetry axis). Recent
      advances in studies of the hepatitis B virus (HBV) core protein attest the
      convergence of the segments preceding the protamine region, around the symmetry
      axis, where five or six HBc protein subunits converge. We report a mutation study
      of the region that we have suggested forms an arm-like structure, which reveals
      that a single mutation, Pro-138 --> Gly, prevents the full-length HBV core
      protein self-assembling into particles.

PMID- 9519839
TI  - Extensive analysis of duplicated-inverted hepatitis B virus integrations in human
      hepatocellular carcinoma.
AB  - Hepatitis B virus (HBV) DNA is found chromosomally integrated into the genome of
      the majority of hepatocellular carcinomas (HCC) arising in chronic HBV carriers
      suggesting that, in some instances, viral sequences may be directly responsible
      for oncogenic conversion. In an attempt to clarify the oncogenic potential of
      integrated HBV sequences, we performed an extensive analysis of two single
      integrations present in HCC which developed in non-cirrhotic livers from HBsAg
      positive Korean patients. In both cases, integrated viral sequences were
      characterized by a duplicated-inverted configuration involving the flanking
      cellular sequences, a pattern consistently found in many amplicons isolated from
      mammalian cells. Integration sites are characterized by an AT-rich content and
      the presence of topoisomerase I and II cleavage target sequences as well as other
      recombination-prone motifs. The chromosomal locations of the integration sites
      were determined as 8q13 and 10q22 in the human genome, two regions known to
      harbour genes involved in tumorigenesis. The cis-activating potential of the
      integrations in their original configuration was also investigated in a transient
      transfection assay in HepG2 cells. Integrated sequences, rather than activating
      heterologous promoters, show either no activity or a weak tendency to inhibit
      activation of neighbouring reporter genes. The implications of our findings for
      the understanding of primary liver cancer development are discussed.

PMID- 9519840
TI  - Cerebral targeting indicates vagal spread of infection in hamsters fed with
      scrapie.
AB  - The pathogenesis of scrapie and other transmissible spongiform encephalopathies
      (TSEs) following oral uptake of agent is still poorly understood and can best be
      studied in mice and hamsters. The experiments described here further extend the
      understanding of the pathways along which infection spreads from the periphery to
      the brain after an oral challenge with scrapie. Using TSE-specific amyloid
      protein (TSE-AP, also called PrP) as a marker for infectivity,
      immunohistochemical evidence suggested that the first target area in the brain of
      hamsters orally infected with scrapie is the dorsal motor nucleus of the vagus
      nerve (DMNV), rapidly followed by the commissural solitary tract nucleus (SN).
      The cervical spinal cord was affected only after TSE-AP had been deposited in the
      DMNV, SN and other medullary target areas. For the first time, these results
      demonstrate conclusively that, in our animal model, initial infection of the
      brain after oral ingestion of scrapie agent occurs via the vagus nerve, rather
      than by spread along the spinal cord.

PMID- 9519841
TI  - Effect of repeated oral infection of hamsters with scrapie.
AB  - The development of a transmissible spongiform encephalopathy upon uptake of the
      infectious agent in feed was studied in the model system scrapie in hamsters.
      Compared to single dosing, repeated dosing caused disease at a considerable
      higher incidence. The risk of infection was higher when the time interval between
      repetitive dosing was short. There was a statistically significant trend of
      clearance of infectivity with time.

PMID- 9519842
TI  - High-level expression of Amsacta moorei entomopoxvirus spheroidin depends on
      sequences within the gene.
AB  - Spheroidin (SPH) is the most highly expressed gene of the entomopoxvirus isolated
      from Amsacta moorei (AmEPV). The level of expression of poxvirus genes is
      believed to be governed in large part by the promoter. Poxvirus promoters
      generally consist of approximately 40 bp which frequently terminate at the 3' end
      with a translation initiating TAAATG sequence. We have examined the requirements
      for high levels of SPH gene expression by constructing AmEPV recombinants
      containing either the SPH promoter or the late vertebrate poxvirus promoter
      derived from the cowpox virus A-type inclusion (ATI) gene. In addition, we have
      examined SPH promoter derivatives which extend beyond the 3' TAAATG to include 2
      or 20 bp of the 5' coding sequence of the SPH gene. Examination of insect cells
      infected with these AmEPV ATI-lacZ or SPH-lacZ recombinants suggests that ATI
      lacZ expression begins 12 h before and is essentially complete prior to any SPH
      lacZ expression, allowing functional distinction between the ATI and SPH
      promoters and implying that different factors regulate the two promoters within
      the insect environment. SPH promoter-regulated expression is significantly
      enhanced within infected insect cells by including the additional 20 bp of the N
      terminal SPH coding sequences as part of the promoter. However, when any of the
      SPH promoter constructs, including those containing the downstream sequences,
      were inserted into vaccinia virus, only very low levels of beta-galactosidase
      expression were observed. These results imply that downstream coding sequences
      within the SPH gene enhance SPH gene expression only within the insect
      environment.

PMID- 9519843
TI  - Assembly of Amsacta moorei entomopoxvirus spheroidin into spheroids following
      synthesis in insect cells using a baculovirus vector.
AB  - The gene encoding the major occlusion body protein, spheroidin, of Amsacta moorei
      entomopoxvirus (AmEPV) was introduced into a baculovirus vector under control of
      the polyhedrin gene promoter. A recombinant virus produced large, ovoid occlusion
      body-like structures in both Spodoptera frugiperda and Trichoplusia ni cells.
      These structures resembled the spheroids found in AmEPV-infected Lymantria dispar
      cells, except they were devoid of virus particles and were not surrounded by a
      membrane- or envelope-like structure. These results were confirmed by
      immunofluoresence microscopy and Western blotting using a specific antipeptide
      antibody to spheroidin, and suggest that the supramolecular assembly of spheroids
      is not dependent on other EPV-encoded gene products. Transmission electron
      microscopy and subcellular fractionation experiments revealed that the spheroid
      like structures were assembled in both the nucleus and cytoplasm of the
      recombinant virus-infected cells. This contrasts with the solely cytoplasmic
      localization found in AmEPV-infected cells.

PMID- 9519844
TI  - The pnk/pnl gene (ORF 86) of Autographa californica nucleopolyhedrovirus is a non
      essential, immediate early gene.
AB  - Autographa californica nucleopolyhedrovirus (AcMNPV) ORF 86, located within the
      HindIII C fragment, potentially encodes a protein which shares sequence
      similarity with two T4 bacteriophage gene products, RNA ligase and polynucleotide
      kinase. This AcMNPV gene has been designated pnk/pnl but has yet to be assigned a
      function in virus replication. It has been classified as an immediate early virus
      gene, since the promoter was active in uninfected insect cells and mRNA
      transcripts were detectable from 4 to 48 h post-infection and in the presence of
      cycloheximide or aphidicolin in virus-infected cells. The extremities of the
      transcript have been mapped by primer extension and 3' RACE-PCR to positions -18
      from the translational start codon and +15 downstream of the stop codon. The
      function of pnk/pnl was investigated by producing a recombinant virus
      (Acdel86lacZ) with the coding region replaced with that of lacZ. This virus
      replicated normally in Spodoptera frugiperda (Sf 21) cells, indicating that
      pnk/pnl is not essential for propagation in these cells. Virus protein production
      in Acdel86lacZ-infected Sf 21 cells also appeared to be unaffected, with normal
      synthesis of the IE-1, GP64, VP39 and polyhedrin proteins. Shut-down of host
      protein synthesis was not abolished in recombinant infection. When other
      baculovirus genomes were examined for the presence of pnk/pnl by restriction
      enzyme digestion and PCR, a deletion was found in AcMNPV 1.2, Galleria mellonella
      NPV (GmMNPV) and Bombyx mori NPV (BmNPV), suggesting that in many isolates this
      gene has either never been acquired or has been lost during genome evolution.
      This is one of the first baculovirus immediate early genes that appears to be
      nonessential for virus survival.

PMID- 9519845
TI  - Identification of artichoke mottled crinkle virus (AMCV) proteins required for
      virus replication: complementation of AMCV p33 and p92 replication-defective
      mutants.
AB  - Mutagenesis of the artichoke mottled crinkle virus (AMCV) genome and
      complementation studies between replication-defective mutants were undertaken to
      identify viral protein(s) essential for AMCV replication. Inoculation of
      Nicotiana benthamiana protoplasts with mutant transcripts revealed that null
      mutations in ORFs 1 [tA33(-)], 2 [tA92(-)] and 6 [tA7(-)], as well as an ORF 2
      mutation [tA92GED] in the GDD motif of the 92 kDa protein, the putative
      replicase, prevented accumulation of detectable levels of progeny RNA.
      Conversely, mutations of ORFs 3 [tA41(-)], 4 [tA21(-)] and 5 [tA19(-)] did not
      substantially affect the accumulation of AMCV genomic and subgenomic RNAs of both
      positive and negative polarity. Inoculation of N. benthamiana plants with
      transcripts impaired in replication revealed that tA92(-) and tA7(-) mutants lead
      to replicating pseudorevertants. Functional analysis of these pseudorevertants
      showed that: (i) the double stop codon introduced at the end of ORF 1 to prevent
      the translational readthrough of the 92 kDa protein reverted to a single amber,
      ochre or opal codon, giving rise to viable genomes; (ii) the putative 7 kDa
      protein is not essential for genome viability, although the RNA region spanning
      ORF 6 plays a role in cis in replication. Finally, the two replication-defective
      mutants tA33(-) and tA92(-) complemented when co-inoculated to N. benthamiana
      protoplasts, definitively proving that the 33 kDa protein is essential for
      tombusvirus genome replication. Analysis of viral RNAs from the coinfection
      experiments showed that tA92(-) was preferentially amplified over tA33(-).

PMID- 9519846
TI  - Sucrose acetate isobutyrate (SAIB): historical aspects of its use in beverages
      and a review of toxicity studies prior to 1988.
AB  - Sucrose acetate isobutyrate (SAIB), a mixture of esters of sucrose with a
      composition approximating the name sucrose diacetate hexaisobutyrate, has been
      used for over 30 yr in many countries as a 'weighting' or 'density-adjusting'
      agent in non-alcoholic carbonated and non-carbonated beverages. As part of the
      demonstration of safety of SAIB as a direct food additive in human diets, a
      program of toxicity testing was started in the late 1950s that culminated in
      extensive studies of SAIB in rodents, monkeys and humans over the last decade.
      This review summarizes the toxicity data, accrued up until 1988, that precede the
      safety studies published elsewhere in this issue. SAIB has been shown to have
      very low acute and chronic toxicities in rats, monkeys, and, except for effects
      on the liver, in dogs at feeding levels of up to 10% in the diet. Slight effects
      seen in rats and monkeys at levels of 10% in the diet are unlikely to be directly
      caused by exposure to SAIB. In dogs, however, SAIB causes decreases in
      bromosulfophthalein (BSP) and indocyanine green (ICG) elimination from the serum
      immediately following a single dose, indicative of interference with biliary
      excretion. On repeated feeding in dogs, SAIB caused increases in serum alkaline
      phosphatase levels, but enzymes indicative of toxic effects on the liver were
      unaffected. On prolonged feeding to dogs, SAIB caused changes in liver morphology
      revealed by electron microscopy. All of these effects were reversed when SAIB was
      withdrawn from the diet. The no-effect level for these effects in dogs was near 5
      mg/kg body weight, but these effects were not seen in rats fed up to 4 g/kg body
      weight/day, monkeys fed up to 10 g/kg body weight/day, or humans fed up to 20
      mg/kg body weight/day. The toxicity and pharmacological studies in dogs, rats and
      monkeys suggest that the effect of SAIB on biliary excretion and liver morphology
      in dogs is essentially pharmacological rather than toxicological in nature and
      that the difference between the effects in dogs at levels as low as 5 mg/kg body
      weight/day, and the lack of effects in rats or monkeys at levels up to 10
      g/kg/day is not merely a quantitative difference between species, but an absolute
      qualitative difference.

PMID- 9519847
TI  - Metabolism and pharmacokinetics of sucrose acetate isobutyrate (SAIB) and sucrose
      octaisobutyrate (SOIB) in rats, dogs, monkeys or humans: a review.
AB  - Sucrose acetate isobutyrate (SAIB), a mixture of esters of sucrose with a
      composition approximating the name sucrose diacetate hexaisobutyrate, has been
      used for over 30 years in many countries as a 'weighting' or 'density-adjusting'
      agent in non-alcoholic carbonated and non-carbonated beverages. As part of the
      demonstration of safety of SAIB as a direct food additive in human diets, a
      number of metabolism and pharmacokinetic studies have been carried out on SAIB
      and the constituent compound sucrose octaisobutyrate (SOIB). These studies are
      reviewed here in order to present in one volume a complete picture of the safety
      studies that have been done on SAIB relevant to its use as a direct food
      additive. The metabolism and pharmacokinetic studies in rats, dogs and humans
      show that SAIB is extensively metabolized in the gastrointestinal tract, probably
      to sucrose and partially acylated sucrose. Partially acylated sucrose appears,
      along with sucrose, to be readily absorbed from the gut, perhaps with inversion,
      although a considerable portion of ingested SAIB and partially deesterified SAIB
      is eliminated in the faeces. The absorbed materials are readily eliminated in the
      urine and the bile or, after further metabolism, as carbon dioxide and water.
      SOIB is less readily metabolized in the gut of rats, dogs and monkeys than is
      SAIB, suggesting that the presence of acetyl groups facilitates the metabolism of
      fully acylated sucrose. In toto, the studies suggest that humans handle SAIB more
      like rats than like dogs.

PMID- 9519848
TI  - Subchronic toxicity studies of sucrose acetate isobutyrate (SAIB) in the rat and
      dog.
AB  - Preliminary short-term toxicity studies of sucrose acetate isobutyrate (SAIB) in
      the dog demonstrated that addition of this additive to the diet was associated
      with an increase in liver size and elevated serum alkaline phosphatase activity
      with no evidence of pathological change by light microscopy. To determine the
      basis for these changes, a 12-week oral toxicity study of SAIB was conducted in
      the dog and a similar study was performed in the rat. SAIB was fed in the diet to
      groups of six beagle dogs of each sex at 0, 0.5, 1.0, 2.0 and 4.0%. SAIB was also
      fed to groups of 40 Sprague-Dawley rats of each sex at levels of 0, 2.5, 5.0 and
      10.0%. In the rat study, in addition to routine toxicology parameters, hepatic
      microsomal enzyme induction was determined using a zoxazolamine hypnotic test,
      urinary ascorbic acid excretion and determination of hepatic carboxylesterase
      activity. Sodium phenobarbital was fed to groups of 20 rats of each sex at a dose
      of 100 mg/kg body weight/day by gavage as a positive control for hepatic
      microsomal enzyme induction. In the dog study, routine toxicological tests were
      supplemented by tests for bromsulfophthalein (BSP) retention, histochemical
      staining of liver sections for glycogen, phosphorylase, succinate dehydrogenase,
      and acid and alkaline phosphatases. Levels of liver lipid, protein, glycogen and
      carboxylesterase activity were also determined. Electron microscopic examinations
      were made on liver sections from the dog study at the end of the 12-week SAIB
      feeding period and after a 2-week withdrawal period. Administration of SAIB to
      rats did not reveal evidence of any effect on hepatobiliary function, and there
      was no indication of microsomal enzyme induction. Body weight gain of male rats
      fed SAIB was decreased, probably as the result of decreased palatability of the
      diet; SAIB did not affect body weight gain in females. The changes observed in
      the dogs fed SAIB included increased serum alkaline phosphatase activity with no
      change in serum alanine aminotransferase, aspartate aminotransferase or lactic
      dehydrogenase activity and no change in serum electrolyte, serum protein, glucose
      or bilirubin levels. No haematological changes were observed. BSP retention was
      observed at all SAIB dose levels. There were no SAIB-related pathological changes
      in any organ when examined by light microscopy. Examination by electron
      microscope revealed dilatation of bile canaliculi and an increase in smooth
      endoplasmic reticulum compared with controls. Histochemical studies also
      indicated increased enzyme activity of the bile canaliculi. The electron
      microscope-revealed changes were completely reversed during a 2-week treatment
      withdrawal period. The dog study did not establish a no-effect level for changes
      in hepatobiliary function induced by feeding SAIB.

PMID- 9519849
TI  - Oral toxicity and carcinogenicity studies of sucrose acetate isobutyrate (SAIB)
      in the Fischer 344 rat and B6C3F1 mouse.
AB  - Sucrose acetate isobutyrate (SAIB), a food additive used as a flavour emulsion
      stabilizer in citrus-based soft drinks, was evaluated for chronic toxicity in
      B6C3F1 mice and Fischer 344 rats. SAIB dissolved in acetone was blended into
      NIH07 rodent diet at concentrations that were adjusted weekly during the first 12
      to 18 months of the studies so that ingested dose levels per kg body weight were
      constant. Groups of 20 rats per sex were given dose levels of 0.0, 0.0, 0.5, 1.0
      and 2.0 g SAIB/kg body weight for 1 yr, and groups of 50 rats per sex were given
      dose levels of 0.0, 0.0, 0.5, 1.0 and 2.0 g SAIB/kg body weight for 2 yr. Mice
      were fed dose levels of 0.0, 0.0, 1.25, 2.5 and 5.0 g SAIB/kg body weight for 2
      yr. The highest doses fed, equivalent to dietary concentrations of approximately
      5%, were considered to be the maximum concentrations that could be fed without
      risk of nutritional deficiencies. Depressions in body weight gain were noted,
      particularly in female rats during the first 12 to 18 months of the studies.
      Recovery during the last quarter of the 2-yr study suggests that the reduced body
      weight gain was nutritional rather than SAIB-related. There were no differences
      in survival between SAIB-treated rats or mice and controls. Decreased body weight
      gains, primarily in females, but less consistent than those in the rat, were
      noted in the 2-yr mouse study. No signs of toxicity were observed in clinical
      chemistry, haematology, organ weights, gross necropsy findings or light
      microscopy studies in the 1- or 2-yr rat studies. Electron microscopic
      examinations of liver sections from high dose level rats from the 1-yr study also
      revealed no effects of SAIB treatment. There were no significant increases in
      benign or malignant tumours in the long-term rat or mouse carcinogenicity
      studies. The lowest no-observed-adverse-effect level (NOAEL) was 2 g SAIB/kg body
      weight derived from the 1- and 2-yr chronic toxicity studies in the rat.

PMID- 9519851
TI  - Lack of genotoxic effects of sucrose acetate isobutyrate (SAIB).
AB  - Sucrose acetate isobutyrate (SAIB) was tested for potential genotoxic activity in
      four different in vitro assay systems. Two independent trials of a Salmonella
      reverse mutation assay (using strains TA98, TA100, TA1535, TA1537 and TA1538)
      showed no increases in revertant frequencies at doses up to 10,000 microg/plate
      which was non-toxic but exceeded the solubility limit. Similarly, no mutagenic
      response was observed at doses up to 1000 microg/ml at the HGPRT locus in
      cultured CHO cells; SAIB was toxic and its solubility limit was exceeded at 50
      microg/ml. No clastogenic activity was detected in cultured CHO cells at
      concentrations up to 2000 microg/ml. All three preceding in vitro tests were
      conducted both in the presence and absence of Aroclor 1254-induced rat liver S-9
      metabolic activation systems. An unscheduled DNA synthesis assay also was
      performed using rat primary hepatocyte cultures with doses up to 1000 microg/ml,
      and no DNA repair was detectable. Thus, SAIB was stringently tested at doses
      exceeding the solubility limit in culture medium and causing toxicity to CHO
      cells without obtaining any evidence for genotoxic activity as a mutagen,
      clastogen, or DNA-damaging agent.

PMID- 9519850
TI  - 4-week range-finding and 1-year oral toxicity studies of sucrose acetate
      isobutyrate (SAIB) in the cynomolgus monkey.
AB  - Sucrose acetate isobutyrate (SAIB) is used as an emulsion stabilizer in citrus
      based soft drinks. A 4-week range-finding study and a 1-year chronic toxicity
      study were conducted to determine the tolerance and effects of this food additive
      in cynomolgus monkeys. SAIB was administered by gavage in corn oil solutions to
      groups of one monkey of each sex in the range-finding study and four monkeys of
      each sex in the 1-year study. The dose levels employed in both studies were 0,
      500, 1450 and 2400 mg/kg body weight. Control monkeys were given corn oil by
      gavage. Based on the range-finding study, the 2400 mg/kg body weight dose level
      of SAIB was considered to be the highest dose of SAIB in corn oil that would be
      tolerated in a long-term study. No differences were observed between treated and
      control animals in either study with respect to body weight gain, clinical
      chemistry, haematology, organ weights, gross necropsy or light microscopy
      findings that could be attributed to SAIB treatment. Results of specific tests of
      hepatobiliary function in the 1-year study, including serum enzymes, bilirubin
      and bile acids, bromsulfophthalein retention and electron microscopic studies of
      the liver, were also negative. It was concluded that the highest dose level fed,
      2400 mg/kg body weight, was the no-observed-adverse-effect level (NOAEL).

PMID- 9519852
TI  - Sucrose acetate isobutyrate (SAIB): three-generation reproduction study in the
      rat and teratology studies in the rat and rabbit.
AB  - A three-generation reproduction study of sucrose acetate isobutyrate (SAIB) in
      Fischer 344 rats and teratology studies in Fischer 344 rats and New Zealand white
      rabbits were performed. Dietary SAIB concentrations to provide dose levels of 0,
      0.5, 1.0 and 2.0 g/kg body weight were used for the rat studies, and 0, 0.5, 0.85
      and 1.2 g/kg body weight doses of SAIB in corn oil were administered by gavage in
      the rabbit studies. F0 generation male rats were fed SAIB for 10 wk, and female
      rats were fed SAIB for 2 wk prior to mating. F1 generation rats were raised on
      the test diets to maturity, mated to produce F2a litters, and remated to produce
      the F2b litters that were examined for teratology. F2a rats were mated to study
      fertility indices for the F3 pregnancy. A decrease in female fertility compared
      with controls was noted at the highest dose of SAIB during breeding of the F1
      generation to produce the F2a litters. No difference in fertility rate between
      controls and treated animals was noted in the results of the other three matings
      that were performed, and it was concluded that the reduction in female fertility
      was not related to SAIB treatment. No morphological abnormalities of soft tissue
      or skeleton were observed in the rat or rabbit teratology studies. The highest
      dose levels administered, 2.0 g SAIB/kg body weight in the rat and 1.2 g SAIB/kg
      body weight in the rabbit, were considered to be no-observed-adverse effect
      levels (NOAEL).

PMID- 9519854
TI  - Nutritional implications of macronutrient substitutes.

PMID- 9519853
TI  - Effect of sucrose acetate isobutyrate (SAIB) ingestion on the hepatobiliary
      function of normal human male and female volunteers.
AB  - A study of the effects of sucrose acetate isobutyrate (SAIB) ingestion was
      conducted in 13 male and 14 female healthy human volunteers. SAIB, in a gum
      arabic/water emulsion diluted with orange juice, was ingested once daily, at a
      dose of 20 mg SAIB/kg body weight in a total volume of 1.16 ml/kg body weight,
      for a period of 2 wk following a 1-week control period. During the control
      period, the subjects consumed the same preparation without SAIB. The study was
      performed in a single-blind manner, each subject serving as his or her own
      control. Haematology and clinical chemistry tests were conducted on blood samples
      taken on day -6 and day 0 of the control period and at 7 and 15 days during the
      SAIB dosing period. In addition to routine haematology and clinical chemistry,
      specific tests of hepatobiliary function included serum alkaline phosphatase,
      aspartate and alanine aminotransferases, lactic dehydrogenase, gamma
      glutamyltransferase, total and direct bilirubin, bile acids and proteins. None of
      these parameters were affected by ingestion of SAIB. It was concluded that
      ingestion of 20 mg SAIB/kg body weight daily for 14 days does not affect the
      hepatobiliary function of human volunteers.

PMID- 9519855
TI  - Peptide dependence of major histocompatibility complex class II specific
      alloreactive responses.
AB  - Splenic cells from transgenic mice, in which a single peptide is complexed to all
      major histocompatibility complex (MHC) class II molecules, are found to be
      incapable of triggering primary allogeneic mixed lymphocyte/leucocyte reactions
      (MLR) when co-cultured with lymphocytes from MHC class II congenic mouse strains.
      In addition, a single HLA-DR-blocking peptide can completely abrogate the
      capacity of splenocytes from chimeric HLA-DR/H2-E transgenic mice to stimulate
      primary MLR of T cells from wild-type mice. These results indicate that the
      primary alloreactive response is directed against a multitude of peptides
      presented by allogeneic MHC molecules.

PMID- 9519856
TI  - Presence of the IL-1RA allele 2 (IL1RN*2) is associated with enhanced IL-1beta
      production in vitro.
AB  - The genes of the interleukin-1 (IL-1) complex code for three proteins: IL-1alpha,
      IL-1beta and the IL-1 receptor antagonist (IL-1RA). Each of these genes is
      polymorphic and there is increasing evidence that certain alleles are associated
      with increased susceptibility to a given disease of inflammatory nature. In the
      IL-1beta gene there are two base-exchange polymorphisms in positions -511 and
      +3953, and IL-1RA gene has a penta-allelic polymorphic site in intron 2
      containing variable numbers of an 86-bp tandem repeat sequence. As the IL
      1beta/IL-1RA ratio may be critical in the regulation of inflammation, we examined
      whether there are allelic associations between these loci (thus suggesting co
      ordinate regulation) and whether these have an effect on the in vitro production
      of IL-1beta. We found that the IL-1RA allele 2 (IL1RN*2) is associated with the
      presence of allele 2 of the IL-1beta gene (position -511) and with the absence of
      allele 2 of the IL-1beta gene (position +3953). Mononuclear cells from carriers
      of allele 2 (position -511) and non-carriers of allele 2 (position +3953) had a
      slight, but non-significant, elevated capacity to produce IL-1beta in vitro.
      However, IL-1RA allele 2 strongly increased in vitro production of IL-1beta,
      regardless of the presence or absence of these alleles. Taken together, these
      data suggest that the known allelisms in the IL-1beta gene are not major
      regulators of the in vitro IL-1beta production, but the IL-1RA allele 2 (or an
      unknown allele strongly associated with it) has a decisive role.

PMID- 9519857
TI  - Birth of the major histocompatibility complex.

PMID- 9519859
TI  - Do chickens immunized with bacterial immunoglobulin G-binding proteins produce
      rheumatoid factor-like antibodies?
AB  - An association between the production of rheumatoid factor (RF)-like antibodies
      in animals immunized with bacterial immunoglobulin (Ig)G-binding proteins has
      been noted. Three potential explanations have been proposed: (1) altered host IgG
      due to binding of the immunogen; (2) B-cell superantigenic properties of the
      binding proteins; and (3) idiotype-anti-idiotype response leading to an antibody
      which acts as an antigen mimic. In order to distinguish among these
      possibilities, it is necessary to carry out studies in animals whose IgG does not
      react with the IgG-binding protein immunogen. Consequently, we have determined
      the effects of immunizing chickens with a purified group C streptococcal IgG
      binding protein, FcRc, a bacterium expressing this protein, and appropriate
      control immunogens. The results of these studies provided evidence for production
      of specific antibodies to FcRc in groups of chickens immunized with either the
      pure protein or bacteria expressing the protein. No significant association with
      production of RF-like antibodies was noted, favouring the altered IgG-binding
      explanation for the association between RF-like antibodies and immunization with
      the bacterial IgG-binding proteins.

PMID- 9519860
TI  - Expression of chL12 surface antigen is associated with cell survival in the avian
      bursa of Fabricius.
AB  - During B-cell development in the avian bursa of Fabricius most of the developing
      B cells die by apoptosis and only a minority survive to emigrate into the
      periphery. Recently, it has been shown that when developing bursal cells become
      mature and ready to migrate they start to express chL12 antigen. The expression
      of this cell-surface molecule was found to be associated with the survival of the
      bursal cells both after in vitro culture and after in vivo cyclophosphamide (CY)
      treatment. The frequency of early apoptotic cells in freshly isolated bursal
      cells was found to be high. The high susceptibility of these cells to apoptosis
      is in line with the finding of low bcl-2 mRNA expression. We conclude that
      expression of avian chL12 antigen is associated with the survival of bursal
      cells.

PMID- 9519858
TI  - Phenotypic convergence and divergence of surface immunoglobulin and CD40 signals.
AB  - Both anti-CD40 antibodies and anti-immunoglobulin (Ig) coupled to Sepharose
      induced proliferation of resting B cells and suppressed lipopolysaccharide (LPS)
      induced B-cell differentiation to immunoglobulin secretion at comparable levels
      determined with the plaque-forming assay and Ig RNA steady state levels. Anti
      CD40 antibodies also increased the proliferation of B cells stimulated by T
      helper cells in vitro while suppressing their differentiation to Ig secretion.
      Further, B cells preactivated by anti-Ig, anti-CD40 or a combination of the two
      mitogens could be restimulated by anti-CD40 but not by anti-Ig antibodies.
      Phenotypic divergence of Ig and CD40 signals regarding surface expression of
      activation markers was observed. Restimulation of anti-Ig- or anti-CD40
      prestimulated cells with anti-Ig induced apoptosis whereas apoptosis could be
      inhibited when cells were recultivated with anti-CD40.

PMID- 9519861
TI  - Down-regulation of lymphokine synthesis by intravenous gammaglobulin is dependent
      upon accessory cells.
AB  - We have investigated one mechanism by which pooled human IgG preparations for
      intravenous use (i.v.Ig) selectively down-regulates lymphokine synthesis. Effects
      of i.v.Ig on cytokine production were quantified at a cellular level by using an
      immunocytochemical staining technique. Pure T-lymphocyte preparations (from the
      peripheral blood of healthy adults) were separated by the use of magnetic beads
      and were then used in parallel experiments with unfractionated mononuclear cells
      (MNC). Cell activation was induced either by a combination of the protein kinase
      C activator, phorbol 12-myristate 13-acetate (PMA), and the calcium ionophore,
      ionomycin, or by direct ligation of the T-cell receptor, using immobilized anti
      CD3 monoclonal antibody (MoAb). Cells were cultured in the presence or absence of
      i.v.Ig and subsequently harvested and stained for the following cytokines:
      interleukin-2 (IL-2), interferon-gamma (IFN-gamma), tumour necrosis factor-beta
      (TNF-beta) and granulocyte-macrophage colony-stimulating factor (GM-CSF).
      Assessment of the frequencies of positively stained cells was performed by manual
      microscopy and by computerized image analysis. Activation by PMA/ionomycin or by
      immobilized anti-CD3 MoAb induced substantial lymphokine production in both MNC
      and in purified T cells. Addition of i.v.Ig led to a diminished synthesis of all
      of the T-cell products studied in unfractionated MNC preparations, whereas
      production was maintained or occasionally increased in the purified T-cell
      preparations. These findings indicate that the immunomodulatory effect by i.v.Ig
      on T-cell activation and lymphokine production was dependent on accessory cells.

PMID- 9519862
TI  - The effects of leflunomide and cyclosporin A on rejection of cardiac allografts
      in the rat.
AB  - Leflunomide is a new low molecular weight immunosuppressive drug which inhibits
      the enzymes dehydroorotate-dehydrogenase and protein tyrosine kinase, both of
      which are important components in the immune response. As the mechanisms of
      action of leflunomide and cyclosporin A (CsA) are different, we postulated a
      synergistic effect of the two drugs and tested graft survival following
      leflunomide administration alone or in combination with CsA in a rat cardiac
      transplantation model. Low- and high-responder rat strain combinations were used
      in parallel and the experiments were performed both with and without challenge
      with Linomide, an immunomodulator which promotes graft rejection in this model.
      In the low-responder rat strain combination (Piebald Virol Glaxo graft to Dark
      Agouti recipient; PVG to DA), graft survival appeared to be a dichotomous
      variable, being characterized by tolerance or early rejection. Leflunomide (10 or
      5 mg/kg) given for 10 days induced tolerance and CsA did likewise; the addition
      of Linomide abolished the immunosuppressive effect of leflunomide but not that of
      CsA. In the high-responder combination (DA to PVG), no tolerance was seen and
      graft survival was moderately prolonged both after leflunomide and after CsA
      treatment; the addition of Linomide to CsA or to leflunomide (5 mg/kg) abolished
      the immunosuppressive effect of the drugs. However, when CsA-Linomide or
      leflunomide-Linomide were supplemented with the second immunosuppressive drug,
      leflunomide or CsA respectively, graft survival was significantly prolonged (P <
      0.001 in both cases). This suggests leflunomide and CsA have additive potential.

PMID- 9519863
TI  - Flow cytometric analysis of cellular changes in mice after intradermal
      inoculation with a liposome-iscom adjuvanted vaccine.
AB  - As it is not known what changes to leucocyte homeostasis are mandatory for
      effective adjuvant action, the biological relevance of systemic changes elicited
      by different vaccine formulations can only be interpreted in the context of the
      immunological outcomes. We used flow cytometry to quantify the changes in
      leucocyte subsets induced in mice intradermally immunized with SAMA4 (adjuvant
      group), outer membrane proteins (OMP) purified from Actinobacillus
      pleuropneumoniae (OMP antigen group), SAMA4 adjuvanted OMP (OMP vaccine group),
      or phosphate-buffered saline (PBS: control group). This approach allowed direct
      comparisons to be made between the effects of antigen, adjuvant or antigen
      adjuvant complexes on immune effector cell populations. Antigens complexed with
      the liposome-iscom hybrid adjuvant, SAMA4, generated strong antibody responses
      and cytotoxic T-cell activity in animals immunized intradermally, reflecting
      remobilization and recruitment of specific cell populations. Splenomegaly, due to
      granulocytosis, monocytosis and megakaryocytosis, was most prominent in the OMP
      vaccine group. Histological examination of spleen sections confirmed that these
      changes were due primarily to splenic haematopoiesis. Circulating numbers of
      granulocytes and monocytes increased significantly (P < 0.05) in the blood of the
      OMP vaccine group, as did granulocyte numbers in the lungs (P < 0.05). No changes
      in T- and B-cell numbers were detected by flow cytometry in the spleens, lungs or
      blood over the 28-day period in any treatment group. Thymocyte numbers
      (predominantly CD4+CD8+ cells) in the OMP vaccine group fell by 95% within 3 days
      of immunization. Identical cellular responses were obtained when an innocuous
      antigen, ovalbumin, was complexed with SAMA4 instead of OMP, thus demonstrating
      that the adjuvant effects of SAMA4 were due to synergistic interaction between
      antigen and adjuvant and not due to the presence of toxic components. The
      association of strong adaptive immune responses with such complex changes in
      leucocyte homeostasis induced by complexing adjuvant and antigen suggested that
      the changes were important for effective vaccination and were not purely
      circumstantial.

PMID- 9519864
TI  - Decreased expression of signal-transducing CD3 zeta chains in T cells from the
      joints and peripheral blood of rheumatoid arthritis patients.
AB  - Although T cells from patients with rheumatoid arthritis (RA) have previously
      been determined to have poor proliferative responses to a variety of stimuli, the
      underlying mechanism is not known. We have investigated the expression of the
      signal-transducing zeta molecule in subsets of T cells and natural killer (NK)
      cells derived from the peripheral blood mononuclear cells (PBMC) and synovial
      fluid mononuclear cells (SFMC) of RA patients using quantitative flow cytometry,
      Western blot analysis and immunohistochemistry. A decrease of zeta expression was
      apparent in all investigated lymphocyte subsets from the PBMC and SFMC of RA
      patients, as compared to the corresponding subsets from healthy age- and sex
      matched controls. A less pronounced reduction of cell surface-located CD3
      epsilon, CD4 and CD8 was also located in T cells from SFMC as compared to PBMC
      from RA patients. Biochemical demonstration of the low or absent CD3 zeta in PBMC
      from patients with RA was achieved by Western blot analysis. Immunohistochemical
      staining and image analysis also confirmed the low expression of zeta chains in
      synovial tissue of RA patients. The possibility that the decreased expression of
      zeta and of immune functions of T cells from RA patients may be related to the
      presence of free oxygen radicals, as we have previously reported in cancer
      patients, should be considered.

PMID- 9519865
TI  - Characterization of a new IgE-binding 35-kDa protein from birch pollen with cross
      reacting homologues in various plant foods.
AB  - The present investigation was undertaken to obtain molecular data of a new
      immunoglobulin (Ig)E-binding birch pollen protein with a mass of 35 kDa. In a
      previous study, this protein showed IgE cross-reactivity with 34- and 35-kDa
      proteins in apples, pears, carrots, bananas and other exotic fruits. Since the
      protein was N-terminally blocked, it was purified by preparative SDS-PAGE, and
      multiple proteolytic fragments were subsequently generated by in-gel digestion
      with the endoproteinases Glu C, Lys C and Clostripain. After electrophoretic
      separation and blotting onto polyvinylidene difluoride (PVDF), the resulting
      polypeptides were subjected to N-terminal amino acid microsequencing. The
      internal sequences obtained showed a high degree of sequence identity to
      isoflavone reductases (IFR) and isoflavone reductase-like proteins (IRL) from
      several plants which also had a similar size. For a stretch of 25 consecutive
      residues this identity ranged from 56% for IFR from peas and chick peas and an
      IRL from maize, to 80% for a tobacco IRL. A 453 bp fragment was amplified from
      total birch pollen RNA by polymerase chain reaction (PCR) using primers derived
      from the nucleotide sequence of the tobacco IRL. The deduced 151 amino acid
      sequence represented approximately 50% of the protein and confirmed the sequence
      identities obtained by Edman degradation. Moreover, the 25 amino acid sequence
      was included in the cloned fragment. Deduced and determined amino acids showed
      only one mismatch, which was due to a single nucleotide exchange. At the antibody
      level, the immunological relationship of the birch pollen protein to IRL and IFR
      was demonstrated by immunoblotting with a rabbit antiserum against a pea IFR
      which recognized the same birch protein as patients' IgE. The rabbit antiserum
      also reproduced the cross-reactivity pattern previously observed with patients'
      IgE by recognizing related proteins in specific plant foods, including some
      exotic fruits. We therefore suggest that the 35-kDa birch pollen protein belongs
      to the IFR/IRL family and represents a minor allergen, possibly being responsible
      for less common pollen-related food allergies in patients allergic to birch
      pollen.

PMID- 9519866
TI  - Identification of a C-->T mutation in the reactive-site coding region of the C1
      inhibitor gene and its detection by an improved mutation-specific polymerase
      chain reaction method.
AB  - Mutations in the C1-inhibitor (C1-INH) gene, leading to low functional levels of
      C1-inhibitor protein, cause hereditary angioedema (HAE). The disease is
      characterized by episodic edema in a number of organs. Typically, swellings occur
      in extremities and face, often accompanied by crampy abdominal pain. Laryngeal
      edema may lead to suffocation. Type II HAE patients have low functional C1-INH
      values stemming from only one normal allele. Antigenic C1-INH values, however,
      are normal or increased owing to the presence of a dysfunctional protein from the
      mutated allele. The mutations are usually found in exon 8 coding for the amino
      acids near the reactive centre (P1). Previously, no mutations in the C1-INH gene
      had been published from the Scandinavian countries. In this work, exon 8 of the
      C1-inhibitor gene was sequenced in members of two different kindreds, from
      western and northern Norway, who were suffering from HAE type II. A common point
      mutation was found within the bait region encoding the reactive centre. The codon
      CGC was converted to TGC at position 17970, corresponding to an Arg-->Cys
      replacement which reportedly is the second most frequent type II HAE mutation.
      This information was utilized to develop a mutation-specific polymerase chain
      reaction (PCR) for the identification of affected family members. The antisense
      17-mer primer (5'-AAGACCAGCAGGGTGCA-3') was successfully applied and AmpliTaq
      Gold was used in the PCR.

PMID- 9519867
TI  - Association of HLA B27 with benign clinical course of nephropathia epidemica
      caused by Puumala hantavirus.
AB  - Both the severe course of nephropathia epidemica (NE) caused by Puumala
      hantavirus, and the fast progression of human immunodeficiency virus (HIV)
      disease, are associated with the HLA B8 DRB1*0301 haplotype. As HLA B27, on the
      contrary, is associated with the slow progression of HIV disease, we wanted to
      test whether the same is true for NE. Only six (8%) NE patients, half the figure
      expected, had the HLA B27 allele in 74 randomly selected hospital-treated
      patients. All six had a benign overall clinical course of NE; none had any severe
      complications, the severity of renal failure was also mild, and the treatment
      time at the hospital was half that needed for HLA B27- patients (P = 0.004).
      Patients who were HLA B27 had maximal blood leucocyte count > 10.000 x 10(9)/L (P
      = 0.020) more often, probably reflecting differences in immune response. Thus,
      similar HLA associations can be found in both HIV infection and NE caused by
      Puumala virus.

PMID- 9519868
TI  - Structural, molecular and immunological properties of linear B-cell epitopes of
      Ro60KD autoantigen.
AB  - Antibodies to Ro60KD protein are found with high frequency in sera from patients
      with systemic lupus erythematosus (SLE) and primary Sjogren's syndrome (pSS). Two
      major epitopes of the Ro60KD antigen, the TKYKQRNGWSHKDLLRSHLKP (169-190) and the
      ELYKEKALSVETEKLLKYLEAV (211-232), were synthesized and their antigenic and
      structural properties were studied. Using a large panel of SLE and pSS patients'
      sera, it was found that the anti-Ro60KD reactivity of both Ro60KD epitopes is
      rather limited (approximately 45%), although they retain their original disease
      specificity. The epitope p.169-190 possessed sequence similarity with the peptide
      RPDAEYWNSQKDLLEQKRGR, shared in the beta-chain of different HLA-DR molecules,
      among them the HLA-DR3 (which is associated with anti-Ro/Sjogren's syndrome A
      (SSA) response in patients with SLE). The antigenicity of the HLA-DR3
      RPDAEYWNSQKDLLEQKRGR peptide was found to be similar to the 169-190 homologous
      Ro60KD epitope, recognized mainly by SLE sera. Structural studies showed that the
      211-232 Ro60KD epitope exhibits pronounced helical characteristics, while the 169
      190 epitope and the HLA-DR3 homologous peptide possess a somewhat lower
      percentage of alpha-helix. A beta-folded structure was identified in the latter
      two peptides. Although the diagnostic value of the reported Ro60KD epitopes seems
      to be rather limited, correlations with other ribonucleoprotein epitopes
      (La/Sjogren's syndrome B, Ro52KD) may prove complementary to each other and
      valuable in clinical use. The ordered structure of the HLA-DR3 homologous
      peptide, exposed to the autoantibody binding, may offer an initiative in further
      investigation of the role of the HLA haplotypes, associated with the anti-Ro/SSA
      response, in the autoimmune stimulus.

PMID- 9519869
TI  - Small contribution of G1 checkpoint control manipulation to modulation of p53
      mediated apoptosis.
AB  - Deregulation of the S-phase promoting E2F-1 transcription factor has been shown
      to cooperate with p53 to induce apoptosis. BaF3 cells undergo rapid, p53
      dependent apoptosis when irradiated in the absence of IL-3. Rapid apoptosis
      induced by ionizing radiation (IR) coincides with attenuated p21(WAF1/Cip1)
      induction. Failure to adequately induce p21 could result in inappropriate release
      of E2F from Rb which may then cooperate with p53 to induce apoptosis in cells
      deprived of growth factor. We engineered BaF3 cells to express exogenous p21 and
      tested whether overexpressing p21 in cells irradiated in the absence of IL-3
      protects from IR-induced apoptosis. Enforced p21 expression resulted in a
      consistent, but partial, protection of cells from undergoing IR-induced
      apoptosis. However, deregulating E2F activity through expression of HPV E7 failed
      to sensitize cells to IR-induced apoptosis in the presence of IL-3. Together,
      these data strongly suggest that the IL-3-responsive factors which modulate p53
      mediated apoptosis in BaF3 cells are largely independent of G1 cell cycle
      checkpoint control mediated by p21.

PMID- 9519870
TI  - Sequential expression of the MAD family of transcriptional repressors during
      differentiation and development.
AB  - Members of the Myc proto-oncogene family encode transcription factors that
      function in multiple aspects of cell behavior, including proliferation,
      differentiation, transformation and apoptosis. Recent studies have shown that MYC
      activities are modulated by a network of nuclear bHLH-Zip proteins. The MAX
      protein is at the center of this network in that it associates with MYC as well
      as with the family of MAD proteins: MAD1, MXI1, MAD3 and MAD4. Whereas MYC-MAX
      complexes activate transcription, MAD-MAX complexes repress transcription through
      identical E-box binding sites. MAD proteins therefore act as antagonists of MYC.
      Here we report the expression patterns of the Mad gene family in the adult and
      developing mouse. High level of Mad gene expression in the adult is limited to
      tissues that display constant renewal of differentiated cell populations. In
      embryos, Mad transcripts are widely distributed with expression peaking during
      organogenesis at the onset of differentiation. A detailed analysis of their
      pattern of expression during chrondrocyte and neuronal differentiation in vivo,
      and during neuronal differentiation of P19 cells in vitro, shows that Mad family
      genes are sequentially induced. Mad3 transcripts and proteins are detected in
      proliferating cells prior to differentiation. Mxi1 and Mad4 transcripts are most
      abundant in cells that have further advanced along the differentiation pathway,
      whereas Mad1 is primarily expressed late in differentiation. Taken together, our
      data suggest that the different members of the MAD protein family exert their
      functions at distinct steps during the transition between proliferation and
      differentiation.

PMID- 9519871
TI  - Tumour specific regulation of telomerase RNA gene expression visualized by in
      situ hybridization.
AB  - Maintenance of telomere structure by the ribonucleoprotein enzyme telomerase is
      considered central to the development of most human cancers. However, regulatory
      mechanisms governing telomerase expression during oncogenesis are largely
      unknown. We address potential tumour-specific regulation of telomerase RNA gene
      expression by RNA in situ hybridization to over 300 tumour samples of germ cell
      and epithelial origin. Twenty-six per cent of non-small cell lung cancers
      (NSCLC), expressed detectable levels of the telomerase RNA gene (hTR), and
      interestingly expression was almost confined to squamous carcinomas (41%), being
      rare in pulmonary adenocarcinomas and large-cell anaplastic carcinomas (P=0.006).
      Low frequency hTR expression was also associated with adenocarcinoma of the
      breast (13%), and ovary (17%). In comparison, hTR expression was detected in 43%
      of cervical cancers with no significant differences in frequency between squamous
      cell carcinoma and adenocarcinoma or in transitions between intraepithelial
      neoplasia and invasive carcinoma. In contrast to the common epithelial cancers,
      the malignant cells in 73% of testicular germ-cell tumours (seminomas and
      teratomas), expressed hTR consistent with hTR expression in normal testicular
      germ cells. Differentiated tissues within ovarian germ cell tumours and in
      testicular teratomas lacked detectable hTR expression. These studies show that
      different tumour types have distinct patterns of hTR expression, which has
      implications for our understanding of mechanisms regulating telomerase activity
      and for targeting the telomerase RNA component as an anti-cancer therapy.

PMID- 9519872
TI  - Oncogenic potential of a mutant human thyrotropin receptor expressed in FRTL-5
      cells.
AB  - An abnormal stimulation of the cAMP pathway has been recognized as the primary
      event in various pathological situations that lead to goitrogenesis or thyroid
      tumors. Thyroid adenomas are monoclonal neoplasms that become independent of
      thyroid stimulating hormone (TSH) in their secretory function and growth. Mutated
      forms of the TSH receptor (TSHR) and the adenylyl cyclase-activating Gs alpha
      protein, which confer a constitutive activity on these proteins, have been
      observed in human adenomas. The FRTL-5 rat thyroid cell line is a permanent but
      untransformed line; the growth of which depends on the presence of TSH, and at
      least in part, on the stimulation of the cAMP pathway. In order to compare the
      oncogenic potential of the activated mutant Gs alpha protein and the
      constitutively activated TSHR, we have transfected FRTL-5 cells with an
      expression vector bearing either the cDNA of the Gs alpha gene carrying the A201S
      mutation or the cDNA of the TSH receptor carrying the M453T mutation recently
      identified in a case of congenital hyperthyroidism. The expression of these two
      cDNAs was driven by the bovine thyroglobulin gene promoter. We show that,
      although the expression of both the Gs alpha or TSHR mutant proteins leads to TSH
      independent proliferation and to constitutive cAMP accumulation in FRTL-5 cells,
      only the mutant TSHR is able to induce neoplastic transformation, as demonstrated
      by growth in semi-solid medium and tumorigenesis in nude mice.

PMID- 9519873
TI  - Expression of RET 3' splicing variants during human kidney development.
AB  - The mature mammalian kidney arises through a series of reciprocal inductive
      interactions between two different cell groups, the ureteric bud epithelium and
      the metanephric mesenchyme. The RET receptor tyrosine kinase is required for
      induction and development of the metanephric kidney. Differential splicing at the
      3' end of RET results in transcripts encoding three isoforms that differ with
      respect to their C-terminal 9 (RET9), 51 (RET51) or 43 (RET43) amino acids. In
      vitro assays have identified differences in the abilities of the RET9 and RET51
      isoforms to induce differentiation suggesting functional differences between
      these proteins. We examined the relative expression levels of the three RET 3'
      splicing variants in developing human kidney using semi-quantitative RT-PCR. We
      observed consistent expression of the RET9 and RET43 variants in kidney samples
      spanning 7.5 through 24 weeks gestation. At early gestational ages (7.5-8.5
      weeks), RET51 expression was very low (+/-5%) compared to RET9; however, a rapid
      seven fold increase in expression was detected by 9 weeks. Our data suggest that
      RET51 may contribute to differentiation-related events occurring after 8.5 weeks
      gestation rather than to induction of the human kidney.

PMID- 9519874
TI  - A transgenic mouse model for mammary carcinogenesis.
AB  - Missense mutations in the p53 tumor suppressor occur frequently in human breast
      cancer and influence both the prognosis and response to chemotherapy. Amino acid
      175 (equivalent to murine 172) is the second most common site of missense
      mutations in p53 in human breast cancer. Over 95% of these mutations are arginine
      to-histidine (R-H) substitutions resulting in a gain-of-function, and not merely
      a dominant-negative phenotype. Transgenic mice expressing a p53 172(R-H)
      construct targeted to the mammary gland by means of a whey acidic protein (WAP)
      promoter were characterized as a model system in order to determine the specific
      effects of this mutation on mammary tumorigenesis. Although transgene expression
      alone had no apparent effect on normal mammary development, transgenic mice
      treated with the chemical carcinogen dimethylbenz(a)anthracene developed tumors
      with much shorter latency than did control littermates and had a greater tumor
      burden. Tumors arising in transgenic mice did not exhibit either decreased
      apoptosis or increased cell proliferation relative to tumors arising in
      nontransgenic littermates, but did display increased genomic instability. Large
      pleiomorphic nuclei were visible in many tumors from transgenic mice, and DNA
      flow analysis confirmed the presence of significant aneuploid cell populations.
      Since these transgenic mice develop very few spontaneous tumors, while
      accelerating carcinogen-and oncogene-mediated tumorigenesis, this mouse model
      will, therefore, be useful in the investigation of early events in mammary
      tumorigenesis. It may also be used as a preclinical model to test newly developed
      chemotherapeutic strategies.

PMID- 9519875
TI  - Identification of a human homolog of the Drosophila neuralized gene within the
      10q25.1 malignant astrocytoma deletion region.
AB  - The loss of chromosome 10 is the most frequent genetic alteration found in
      malignant astrocytomas. In particular, the long arm of chromosome 10 was
      previously reported to have two or more common deletion regions where tumor
      suppressor genes may be located. In this study, we performed deletion mapping of
      44 malignant astrocytomas using 12 microsatellite markers on chromosome 10q and
      demonstrated that the minimal common region of loss of heterozygosity (LOH) was
      present between D10S192 and D10S566 localized at 10q25.1. Subsequently, we have
      identified a novel gene, termed h-neu, within the region frequently deleted and
      found that h-neu encodes a protein with strong homology to the Drosophila
      neuralized (D-neu) protein. Northern blot and RT-PCR analyses revealed that h-neu
      mRNA was expressed at very low levels in human malignant astrocytoma tissues and
      the majority of glioma cell lines examined, while normal brains expressed h-neu
      transcript. Furthermore, DNA sequencing analysis of the h-neu transcript revealed
      one of the glioma cell lines, U251MG, had a single nucleotide substitution which
      resulted in an amino acid change from glycine (GGC) to serine (AGC) at codon 253.
      The D-neu gene is known to serve a critical function in neurogenesis in
      Drosophila, and loss-of-function mutations produce hyperplasia of primitive
      neuronal cells. These observations led us to hypothesize that h-neu gene plays a
      role in determination of cell fate in the human central nervous system and may
      act as a tumor suppressor whose inactivation could be associated with malignant
      progression of astrocytic tumors.

PMID- 9519876
TI  - The DNA binding domains of the WT1 tumor suppressor gene product and chimeric
      EWS/WT1 oncoprotein are functionally distinct.
AB  - The t(11;22)(p13;q12) translocation associated with desmosplastic small round
      cell tumor results in a chimeric molecule fusing the amino terminal domain (NTD)
      of the EWS1 gene to three of the four carboxy-terminal zinc fingers of the WT1
      tumor suppressor gene. Since the DNA binding domains of WT1 and EWS/WT1 are
      structurally different, we have assessed the functional consequences of the
      EWS/WT1 fusion. We find that the EWS/WT1 protein has a higher binding affinity
      for a given recognition target than the WT1 product. This is unlike other fusion
      products involving translocation of the NTD of EWS to DNA binding domains in
      which DNA binding specificity and affinity is not changed. We demonstrate that
      EWS/WT1 is a nuclear protein and that the NTD of EWS contains (a) nuclear
      localization signal(s). We also find that the integrity of a domain within the
      WT1 zinc fingers, responsible for mediating interaction between WT1 and the
      transcriptional repressor par-4, is disrupted in the EWS/WT1 fusion product.
      Deletion analysis of the NTD of EWS indicated that integrity of the entire domain
      was necessary to achieve full transactivation potential.

PMID- 9519877
TI  - Identification of a BRCA1-associated kinase with potential biological relevance.
AB  - A biochemical approach was used to identify proteins which interact with human
      BRCA1. Through this work, a kinase activity which co-purifies with BRCA1 has been
      identified. This kinase activity, which phosphorylates BRCA1 in vitro, was
      originally identified in Sf9 insect cells but is also present in cells of human
      origin including breast and ovarian carcinoma cell lines. The BRCA1 kinase
      activity in vitro is associated with a fragment of BRCA1 encompassing amino acids
      329-435. This peptide is also phosphorylated in various human cell lines. A
      computer-assisted sequence analysis revealed that this peptide was a potential
      substrate for phosphorylation by PKA, PKC, or CKII. However, phosphorylation by
      these kinases could not be demonstrated in vitro indicating the presence of
      another kinase activity. Phosphorylation in vitro requires a minimal domain of
      BRCA1 encompassing amino acids 379-408. Notably, deletion of this minimal domain
      abolishes growth suppression by BRCA1 indicating that this domain, as well as
      phosphorylation within this domain, may be important for BRCA1 function.

PMID- 9519878
TI  - Effect of simian virus large T antigen expression on cell cycle control and
      apoptosis in rat pleural mesothelial cells exposed to DNA damaging agents.
AB  - Cell cycle progression and apoptosis are controlled by regulatory proteins,
      including p53, of which functional alterations are linked to carcinogenesis.
      Recently, malignant mesothelioma (MM), a primary tumour related to asbestos
      exposure, alternatively to post therapeutic radiations, has proven to be an
      important problem in oncogenesis. The p53 protein does not seem mutated or
      deleted in MM but a possible inactivation by binding to other proteins [mdm2;
      SV40 large T antigen (Tag)] has been suggested. The present work investigated
      cell cycle regulation in normal rat pleural mesothelial cells (RPMC) and in RPMC
      expressing Tag (RPMC-TSV40), under exposure to asbestos and radiations. In RPMC,
      these agents induced activation of cell cycle checkpoints located at G1/S and
      G2/M and/or mitosis but a lack of control at G1/S was found in RPMC-TSV40. A loss
      of G2/M control may account for the formation of micronuclei observed after
      exposure of RPMC-TSV40 to radiations. In RPMC-TSV40 the enhancement of abnormal
      mitoses and apoptosis after asbestos exposure, in comparison with RPMC, suggests
      a loss of mitotic control and a p53-independent mechanism of apoptosis. Thus Tag
      expression in mesothelial cells might have both adverse and beneficial effects by
      impairing the control of DNA integrity and enhancing apoptosis respectively.

PMID- 9519880
TI  - Functional capabilities of molecular network components controlling the mammalian
      G1/S cell cycle phase transition.
AB  - The molecular interactions implicated in the mammalian G1/S cell cycle phase
      transition comprise a highly nonlinear network which can produce seemingly
      paradoxical results and make intuitive interpretations unreliable. A new approach
      to this problem is presented, consisting of (1) a convention of unambiguous
      reaction diagrams, (2) a convenient computer simulation method, and (3) a quasi
      evolutionary method of probing the functional capabilities of simplified
      components of the network. Simulations were carried out for a sequence of
      hypothetical primordial systems, beginning with the simplest plausibly functional
      system. The complexity of the system was then increased in small steps, such that
      functionality was added at each step. The results suggested new functional
      concepts: (1) Rb-family proteins could store E2F in a manner analogous to the way
      a condenser stores electric charge, and, upon phosphorylation, release a large
      wave of active E2F; (2) excessive or premature cyclin-dependent kinase activities
      could paradoxically impair E2F activity during the G1/S transition period. The
      results show how network simulations, carried out by means of the methods
      described, can assist in the design and interpretation of experiments probing the
      control of the G1/S phase transition.

PMID- 9519879
TI  - The thiol crosslinking agent diamide overcomes the apoptosis-inhibitory effect of
      Bcl-2 by enforcing mitochondrial permeability transition.
AB  - In several different cell lines, Bcl-2 prevents the induction of apoptosis (DNA
      fragmentation, PARP cleavage, phosphatidylserine exposure) by the pro-oxidant ter
      butylhydroperoxide (t-BHP) but has no cytoprotective effect when apoptosis is
      induced by the thiol crosslinking agent diazenedicarboxylic acid his 5N,N
      dimethylamide (diamide). Both t-BHP and diamide cause a disruption of the
      mitochondrial transmembrane potential delta psi(m) that is not inhibited by the
      broad spectrum caspase inhibitor z-VAD.fmk, although z-VAD.fmk does prevent
      nuclear DNA fragmentation and poly(ADP-ribose) polymerase cleavage in these
      models. Bcl-2 stabilizes the delta psi(m) of t-BHP-treated cells but has no
      inhibitory effect on the delta psi(m) collapse induced by diamide. As compared to
      normal controls, isolated mitochondria from Bcl-2 overexpressing cells are
      relatively resistant to the induction of delta psi(m) disruption by t-BHP in
      vitro. Such Bcl-2 overexpressing mitochondria also fail to release apoptosis
      inducing factor (AIF) and cytochrome c from the intermembrane space, whereas
      control mitochondria not overexpressing Bcl-2 do liberate AIF and cytochrome c in
      response to t-BHP. In contrast, Bcl-2 does not confer protection against diamide
      triggered delta psi(m) collapse and the release of AIF and cytochrome c. This
      indicates that Bcl-2 suppresses the permeability transition (PT) and the
      associated release of intermembrane proteins induced by t-BHP but not by diamide.
      To further investigate the mode of action of Bcl-2, semi-purified PT pore
      complexes were reconstituted in liposomes in a cell-free, organelle-free system.
      Recombinant Bcl-2 or Bcl-X(L) proteins augment the resistance of reconstituted PT
      pore complexes to pore opening induced by t-BHP. In contrast, mutated Bcl-2
      proteins which have lost their cytoprotective potential also lose their PT
      modulatory capacity. Again, Bcl-2 fails to confer protection against diamide in
      this experimental system. The reconstituted PT pore complex itself cannot release
      cytochrome c encapsulated into liposomes. Altogether these data suggest that pro
      oxidants, thiol-reactive agents, and Bcl-2 can regulate the PT pore complex in a
      direct fashion, independently from their effects on cytochrome c. Furthermore,
      our results suggest a strategy for inducing apoptosis in cells overexpressing
      apoptosis-inhibitory Bcl-2 analogs.

PMID- 9519881
TI  - Isolation of canine p53 cDNA and detailed characterization of the full length
      canine p53 protein.
AB  - The p53 tumour suppressor protein plays a central role in the maintenance of
      genomic integrity. Mutations of the p53 gene are found in a number of canine
      cancers and many contribute to tumour formation. Here we describe isolation and
      expression of the complete wild type canine p53 cDNA. The encoded full length
      canine p53 protein displays strong sequence homology with p53 proteins from other
      higher vertebrates. Canine p53 protein produced in vitro was shown to recognize
      and bind to p53-specific DNA targets derived from the p21 and GADD45 promoters
      and to a consensus p53 binding site. We also show that canine p53 associates with
      oligonucleotides representing damaged DNA sites and undergoes proteolytic
      cleavage similar to that described for murine and human p53 proteins. Finally, we
      show that the canine p53 protein is able to transcriptionally activate a p53
      dependent reporter gene in vivo. The results suggest that canine p53 is similar
      both in structure and function to human p53 and that canine cancer may provide a
      useful clinical model in the search for effective anti-cancer therapies based on
      p53.

PMID- 9519883
TI  - No evidence for the H133Y mutation in SONIC HEDGEHOG in a collection of common
      tumour types.
AB  - The human homologue of the Drosophila segment polarity gene patched is mutated in
      the cancer predisposition syndrome naevoid basal cell carcinoma syndrome (NBCCS),
      as well as in several types of tumour associated with the disorder. It was
      recently reported that a single recurrent mutation in the SONIC HEDGEHOG gene,
      which encodes the PATCHED ligand, was found in one of 43 basal cell carcinomas
      (BCCs), one of 14 medulloblastomas and one of six breast carcinomas analysed (Oro
      et al., 1997). We have searched extensively for this same mutation in a large
      collection of BCCs, medulloblastomas and carcinomas of the breast, ovary and
      colorectum and have failed to detect the mutation in any sample analysed.

PMID- 9519884
TI  - Extracellular acidosis and high levels of carbon dioxide suppress synaptic
      transmission and prevent the induction of long-term potentiation in the CA1
      region of rat hippocampal slices.
AB  - Long-term potentiation (LTP) is a long-lasting increase in synaptic strength
      induced by high frequency stimulation. LTP may participate in learning and memory
      formation. In many synaptic systems, LTP is dependent on intact function of N
      methyl-D-aspartate (NMDA) receptors. NMDA receptors may be inhibited in different
      conditions involving also extracellular acidosis. A decrease in the extracellular
      pH accompanies many pathological states such as ischemia, hypoxia, and the CNS
      injury. The study was designed to determine whether comparable extracellular acid
      base imbalances are able to interfere with the LTP induction. Hippocampal slices
      from adult rats were stimulated with high frequency stimulation (1 x 100 Hz/1 s)
      at Schaffer collateral-commissural synaptic system in the environment with
      different pH (6.7-7.8) and the field responses were recorded in CA1. Acidosis was
      achieved by supplying excessive CO2 or by HCO3-decrease in standard bicarbonate
      containing buffer or by a direct acidification of the buffer containing Na-HEPES.
      Invariably, all forms of acidification suppressed the efficacy of normal, low
      frequency synaptic transmission and prevented the induction of LTP in a
      reversible manner; i.e., after reperfusion of the slices at pH 7.3 and
      restimulation, there was a return of synaptic transmission back to baseline, and
      a significant amount of LTP occurred. In contrast, alkalization to pH 7.8,
      although enhancing synaptic transmission efficacy, did not further increase the
      LTP magnitude compared to control environment with pH 7.3. The results suggest
      that extracellular acidosis associated with several pathological conditions in
      the CNS may significantly diminish the LTP induction, and thus negatively affect
      all physiological processes that utilize LTP.

PMID- 9519882
TI  - The CXXC Zn binding motifs of the human papillomavirus type 16 E7 oncoprotein are
      not required for its in vitro transforming activity in rodent cells.
AB  - The conserved region 3 (CR3) of the E7 protein of human papillomaviruses contains
      two CXXC motifs involved in zinc binding and in the homodimerization of the
      molecule. Studies have suggested that the intact CXXC motifs in the CR3 of HPV16
      and HPV18 E7 are required for the in vitro transforming activity of these
      proteins. CR3 also contains a low affinity pRb binding site and is involved in
      the disruption of the E2F/Rb1 complex. E7 is structurally and functionally
      related to Adenovirus E1A protein, which also has two CXXC motifs in CR3.
      However, the Ad E1A transforming activity appears to be independent of the
      presence of such domains. In fact, this viral protein exists in vivo as two
      different forms of 289 and 243 amino acids. The shorter Ad E1A form (Ad E1A243),
      where both CXXC motifs are deleted by internal splicing, retains its in vitro
      transforming activity. We have investigated if the HPV16 E7 CR3 can be
      functionally replaced by the Ad E1A243 CR3, which lacks both CXXC motifs. A
      chimeric protein (E7/E1A243) containing the CR1 and CR2 of HPV16 E7 fused to the
      CR3 of Ad E1A 243 was constructed. The E7/E1A243 while not able to homodimerize
      in the S. cerevisiae two-hybrid system retains several of the properties of the
      parental proteins, HPV16 E7 and Ad E1A. It associates with the 'pocket' proteins,
      induces growth in soft agar of NIH3T3 cells and immortalizes rat embryo
      fibroblasts. These data suggest that the CXXC motifs in CR3 of E7 do not play a
      direct role in the transforming properties of this viral protein but probably are
      important for maintaining the correct protein configuration.

PMID- 9519885
TI  - Differential vulnerability of the subiculum and entorhinal cortex of the adult
      rat to prolonged protein deprivation.
AB  - Protein deprivation experienced in adult life leads to deficits in the number of
      hippocampal granule and CA3-CA1 pyramidal cells and to changes in the dendritic
      domain of granule cells and CA3 pyramids. To obtain a more complete insight into
      the effects of malnutrition on the limbic system of the adult rat we have
      analyzed the subiculum and the entorhinal cortex (neuronal layers II, III, and V
      VI) in groups of 8-month-old rats fed with a low-protein diet (8% casein) since
      the age of 2 months and in age-matched control rats. Stereological methods were
      employed to estimate the total number of neurons in the subiculum and layers II,
      III, and V-VI of the entorhinal cortex and the volume of the respective cell
      layers. Moreover, to evaluate whether protein deprivation affects the dendritic
      domains of the neurons from these regions we have analyzed, in Golgi-impregnated
      material, the dendritic trees of the pyramidal cells of the subiculum and of the
      stellate neurons of the entorhinal cortex layer II applying quantitative and
      metric methods. The volume of the subiculum and the total number of its neurons
      were reduced in malnourished animals. In these animals we also found marked
      regressive changes in the apical and basal dendritic trees of the pyramidal
      subicular neurons. However, the spine density was increased in malnourished rats.
      No differences in the volume of the neuronal layers of the entorhinal cortex or
      in the total number of their neurons were found between protein-deprived and
      control rats, and no alterations were depicted in the dendritic trees of the
      stellate neurons of layer II. We can thus conclude that the effects of long-term
      protein deprivation are region specific and that the resulting structural
      alterations are confined to the three-layered components of the hippocampal
      region.

PMID- 9519886
TI  - Analysis of the interaction between arachidonic acid and metabotropic glutamate
      receptor activation reveals that phospholipase C acts as a coincidence detector
      in the expression of long-term potentiation in the rat dentate gyrus.
AB  - We have reported that arachidonic acid and the metabotropic glutamate receptor
      agonist, trans-1-amino-cyclopentyl-1,3-dicarboxylate (ACPD), act in synergy to
      increase release of glutamate from synaptosomes prepared from rat dentate gyrus.
      The observation that prior induction of LTP in perforant path-granule cell
      synapses occluded this synergism suggested that the interaction between
      arachidonic acid and ACPD might trigger the increase in glutamate release that
      accompanies LTP in dentate gyrus. Our objective was to identify the mechanism
      underlying the synergism between arachidonic acid and ACPD in LTP. The data
      indicate that both agents activate phospholipase C(PLC); the arachidonic acid
      induced increase in phospholipase C activation was inhibited by the tyrosine
      kinase inhibitor, genistein, suggesting that PLCgamma, which is stimulated by
      tyrosine phosphorylation may be activated by arachidonic acid. The ACPD-induced
      increase was inhibited by neomycin, indicating the involvement of a G-protein and
      suggesting that PLCbeta may be activated by ACPD. We report that arachidonic acid
      stimulated phosphorylation of the specific tyrosine kinase substrate,
      poly(Glu80,Tyr20) and direct analysis indicated that arachidonic acid increased
      phosphorylation of PLCgamma. PLCgamma phosphorylation was assessed in control
      dentate gyrus and dentate gyrus in which LTP was induced in vivo. We report that
      the tyrosine kinase inhibitor, genistein, blocked expression of LTP and also
      blocked the associated increase in phosphorylation of PLCgamma. The data
      presented here indicate that tyrosine phosphorylation of PLCgamma was
      significantly enhanced following induction of LTP, but in separate experiments,
      in which LTP was inhibited by intraventricular injection of genistein,
      phosphorylation of PLCgamma was inhibited. The evidence presented is consistent
      with the hypothesis that PLC acts as a coincidence detector in LTP. The data
      indicate that PLCbeta is activated by ACPD, PLCgamma is activated by arachidonic
      acid, and coincident activation of both isoforms is necessary to stimulate an
      increase in glutamate release.

PMID- 9519887
TI  - Tracing of the entorhinal-hippocampal pathway in vitro.
AB  - In vitro tract tracing allowing for continuous observation of the perforant path
      is a crucial prerequisite for experimental studies on the entorhinal-hippocampal
      interaction in an organotypic slice culture containing the entorhinal cortex, the
      perforant path, and the dentate gyrus (OEHSC). We prepared horizontal slices of
      the temporal entorhinal-hippocampal region of the rat on a vibratome, and the
      perforant path axons were traced by application of the fluorescent tracer Mini
      Ruby on the entorhinal cortex. After 2 days in vitro (div), the perforant path
      became visible in most cultures. Entorhinal neurons and single perforant fibers
      could be followed to the outer molecular layers of the dentate gyrus by in vitro
      fluorescence microscopy and it was possible to monitor the perforant path
      directly over a period of 25 div. Moreover, ultrastructural analysis proved the
      existence of traced perforant path boutons forming synapses with spines and
      dendritic shafts in the outer molecular layers of the dentate gyrus. Transsection
      of the prelabelled perforant path in vitro resulted in anterograde degeneration
      and subsequent phagocytosis of axonal material by activated microglial cells in
      the zone of denervation. In conclusion, in vitro tracing demonstrates the
      maintenance of the entorhinal-hippocampal pathway in OEHSCs and permits
      monitoring of dynamic changes in the prelabeled perforant path after various
      lesion paradigms, e.g., transsection or neurotoxin treatment. This approach
      permits further studies on the efficacy of neuroprotectants, cytokines, and
      growth factors in the treatment of lesion-induced neuronal degeneration.

PMID- 9519888
TI  - Total number of neurons in the layers of the human entorhinal cortex.
AB  - The total number of neurons in the major laminae of the human entorhinal cortex
      were estimated with a design-based stereological technique, the optical
      fractionator. Detailed descriptions of the laminar organization and the cortical
      limits of the region required for the analysis are provided, along with detailed
      descriptions of the sampling scheme employed. The individual, mean values, and
      variances for estimates made in layers II, III, V, and VI are presented and
      discussed in terms of the precision of the estimation procedure and the results
      of other studies. Neuron numbers were estimated to be about 1 million layer II
      cells, 5 million layer III cells, 2 million layer V cells, and 4 million layer VI
      cells, for a total of slightly more that 13 million neurons in the entorhinal
      cortex. Combined with data from a similar study carried out in the human
      hippocampus, the data presented represent the first rigorous stereological
      evidence of the divergence of entorhinal projections to the hippocampus. The data
      presented also indicate that projections from layer II of the entorhinal cortex
      to the dentate gyrus and CA2/3 and projections from layer III of the entorhinal
      cortex to CA1 differ in the degrees of their divergence.

PMID- 9519889
TI  - Inhibition of human immunodeficiency virus type 1 replication by a bioavailable
      serine/threonine kinase inhibitor, fasudil hydrochloride.
AB  - Replication of human immunodeficiency virus type 1 (HIV-1) is regulated by a host
      transcription factor, nuclear factor kappaB (NF-kappaB). NF-kappaB belongs to a
      group of inducible transcription factors and its activity is regulated by
      multiple cellular signal transduction pathways, including kinases. These kinases
      are known to be involved in signal-induced NF-kappaB activation and in the
      induction of HIV-1 gene expression from latently infected cells. In this study we
      have examined the effect of a newly developed serine/threonine kinase inhibitor,
      fasudil hydrochloride (FH), on the replication of HIV-1. Although FH was
      initially developed as a compound that inhibited a myosin light chain kinase
      (MLCK) and had been approved for clinical use in the treatment of vasospasm after
      subarachnoid hemorrhage, this study shows its efficacy in blocking HIV-1
      replication in latently infected patients. When FH was added to monocytic cell
      lines latently infected with HIV-1, U1 and OM10.1, the induction of HIV-1
      replication by TNF-alpha was blocked at noncytotoxic doses. The IC50 values of
      HIV-1 induction by FH were 9.3 and 24 microM for U1 and OM10.1, respectively.
      Because FH could block TNF-alpha-induced, NF-kappaB-dependent gene expression, as
      examined by the transient luciferase expression assay, the effect of FH was
      considered to be due to the blocking of the signal transduction pathway of NF
      kappaB activation. Although the in vivo effect of FH in blocking HIV-1 induction
      is not yet known, these findings indicate the feasibility of clinical use of FH
      and its derivatives in decreasing viral load to prevent clinical development of
      acquired immunodeficiency syndrome (AIDS) among HIV-1-infected individuals.

PMID- 9519891
TI  - Analysis of a biallelic polymorphism in the tumor necrosis factor alpha promoter
      and HIV type 1 disease progression.
AB  - The relevance of a TNF-alpha promoter polymorphism, a G-to-A polymorphic sequence
      at position-308, was examined to test whether variant alleles of TNF-alpha affect
      susceptibility to infection with HIV-1 and progression to AIDS. Analysis of
      specimens from cohorts of HIV-1 positive homosexual men demonstrated that 3 of
      the 32 (9.4%) HIV-1-infected long-term nonprogressors (LTNPs) were homozygous for
      the uncommon TNF-2 allele compared with 3 of the 196 (1.5%) HIV-1-seronegative
      blood donors and uninfected homosexual men (p < 0.05). There was no difference in
      heterozygosity among HIV-1-seropositive or -seronegative groups, although some of
      the seropositive men heterozygous for the TNF2 genotype were also heterozygous
      for CCR5delta32. However, no significant association was found between TNF
      genotypes and time of survival, CD4 slopes, or viral loads when seroincident (n =
      109) and seroprevalent cases (n = 442) from the Chicago MACS were analyzed.
      Functional analysis of lymphocytes from the seronegative group revealed no
      difference in endogenous or mitogen-induced TNF-alpha production, as well as
      susceptibility to in vitro HIV-1 infection between different TNF-genotype donors.
      These data suggest that TNF genotypes do not play a direct role in HIV-1 disease
      progression; however, they could potentially be part of a multigenic linkage that
      may be involved in delaying progression to AIDS.

PMID- 9519890
TI  - The maximal tolerable intravenous dosage of pentoxifylline in AIDS patients does
      not inhibit lipopolysaccharide-stimulated tumor necrosis factor alpha production.
AB  - Tumor necrosis factor alpha (TNF-alpha) may be involved in the pathogenesis of
      metabolic and endocrine changes in HIV infection. Pentoxifylline (PTX) is able to
      suppress the production of TNF-alpha in vitro. The effect of two dosages of
      intravenously administered PTX on clinical symptoms and ex vivo LPS-stimulated
      TNF-alpha production was evaluated in six clinically stable AIDS patients in a
      saline-controlled study. PTX in a dosage of 1.5 mg/min was tolerated without side
      effects. PTX in a dosage of 2.1 mg/min resulted in intolerable nausea and
      necessitated termination of infusion after 30 min. The average plasma
      concentration of PTX after infusion of 1.5 mg/min for 6 hr was 510+/-56 ng/ml,
      which is considerably below the concentrations that have been reported to
      suppress TNF-alpha production in vitro. No effect of PTX infusion (1.5 mg/min) on
      LPS-stimulated TNF production ex vivo was found. Our conclusion is that the
      maximally tolerated i.v. dosage of PTX in AIDS patients is 1.5 mg/min. LPS
      stimulated ex vivo TNF-alpha production, at the LPS concentrations tested, was
      not inhibited by the plasma concentration of PTX that could be achieved at this
      dosage.

PMID- 9519892
TI  - Serotyping of HIV type 1 infections: definition, relationship to viral genetic
      subtypes, and assay evaluation. UNAIDS Network for HIV-1 Isolation and
      Characterization.
AB  - V3 serotyping refers to a system based on binding of antibody in patient sera to
      V3-loop peptides derived from HIV-1 env genetic subtypes. The V3x serotype
      represents reactivity of serum from an HIV-1-infected patient (regardless of
      viral genetic subtype), which reacts preferentially to a V3 peptide derived from
      the X subtype sequence. We have classified HIV-1 serotypes, determined the
      relationship between the HIV-1 V3 serotypes and viral genetic subtypes in a large
      study (n = 125), and evaluated the performance of three different V3 peptide
      binding assays. Seven HIV-1 V3 serotypes were identified: A, B, B-Br, B-Th, C, D,
      and E. Serotypes B-Br and B-Th represent sera that react specifically to peptides
      derived from Brazilian B (B-Br, GWGR) and Thai B (B-Th, GPGQ) strains. The HIV-1
      V3 B, C, and E serotypes correlated closely with their viral env genetic
      subtypes; 19-26 of 32 B sera (59-79%), 3-4 of 4 C sera (75-100%), and 19-22 of 23
      E sera (83-96%) were identified as serotypes B, C, and E, respectively. In
      contrast, two major V3 serotypes were classified in A sera: A (14-18 of 36 [40
      50%]) and C (12-19 of 36 [33-54%]). Similarly, two major V3 serotypes were
      classified in D sera: B (6-10 of 20 [30-50%]) and D (9-12 of 20 [45-60%]).
      Serotyping of subtype E sera showed the best concordance with genetic subtypes by
      all assays. Overall, HIV-1 V3 serotyping produced consistent results among three
      laboratories. However, HIV-1 V3 serotypes do not distinguish all HIV-1 genetic
      subtypes. The relative biological significance of the V3 serotypes remains to be
      elucidated.

PMID- 9519893
TI  - HIV type 1 in Thailand, 1994-1995: persistence of two subtypes with low genetic
      diversity.
AB  - Extensive transmission of human immunodeficiency virus type 1 (HIV-1) in Thailand
      began in 1988, resulting in an estimated 800,000 cumulative infections by 1994.
      During 1994 and 1995, we collected blood specimens from 215 asymptomatic HIV-1
      infected people with various risk behaviors from nine locations in all four
      regions of Thailand. HIV-1 subtypes and genetic heterogeneity were determined for
      214 strains by a combination of direct DNA sequencing (n = 95), subtype-specific
      oligonucleotide probe testing (n = 201), and V3-loop peptide enzyme immunoassay
      (PEIA) (n = 214). All strains were either env subtype E (175; 81.8%) or B (39;
      18.2%). Of the subtype B isolates, 37 (94.9%) were B' and 2 (5.1%) were more
      typical North American-like B strains (most subtype B strains in Thailand are
      part of a distinct subcluster within the subtype B branch on phylogenetic trees,
      termed B'; formerly Thai B or BB). Of 149 viruses from people with sexual risk
      behaviors from all regions, 146 (98.0%) were subtype E. Of 65 viruses from
      injecting drug users (IDUs), 29 (44.6%) were subtype E and 36 (55.4%) were
      subtype B, including 35 B' strains. There was regional variation in the
      proportions of subtypes E and B' among IDUs. The intrasubtype nucleotide
      divergence within the V3 and flanking regions of the env gene (mid-C2 to the
      start of the V4 region) was low (5.7% for subtype E and 3.1% for subtype B')
      compared with other HIV-1 group M subtypes from different countries. These
      findings of two subtypes with low heterogeneity indicate that Thailand may be a
      desirable setting for evaluating candidate HIV-1 vaccines. The mix of subtype E
      and B' strains among IDUs also offers the opportunity to study phenotypic
      differences between the two subtypes.

PMID- 9519895
TI  - Proliferation-dependent replication in primary macrophages of macrophage-tropic
      HIV type 1 variants.
AB  - We previously demonstrated that completion of reverse transcription in
      macrophages inoculated with the HIV-1 Ba-L variant was established only in the
      subpopulation of cells with proliferative capacity. In our present study we
      further extended this observation with three additional HIV-1 isolates, being the
      macrophage-tropic ADA strain and two primary macrophage-tropic HIV-1 variants
      isolated from cerebrospinal fluid and from bronchoalveolar lavage from AIDS
      patients. On inoculation, irrespective of the virus variant used, elongated
      reverse transcription products could be demonstrated only in macrophages that had
      proliferated during inoculation as evidenced by the incorporation of
      bromodeoxyuridine (BrdU), a thymidine analog. The presence of newly synthesized
      early products of reverse transcription also in the BrdU-negative fraction
      indicated that viral entry is not disturbed in nondividing cells. Our data
      indicate that the process of reverse transcription is dependent on cellular
      conditions that coincide with cell proliferation, and therefore that HIV-1
      replication is restricted to cells with proliferative potential.

PMID- 9519894
TI  - Diversity of the human immunodeficiency virus type 1 envelope glycoprotein in San
      Francisco Men's Health Study participants.
AB  - Multiple genetic subtypes of HIV-1, differing by up to 30% of nucleotides in
      their envelope coding sequences, have been identified in the global epidemic. In
      the United States, where HIV-1 infection with subtype B predominates, the
      interisolate diversity in envelope is 15% or more. It is recognized that
      geographic, temporal, and demographic variables can affect the genetic diversity
      of HIV-1 strains, but there have been few opportunities to evaluate these factors
      by population-based sampling. We have evaluated HIV-1 envelope diversity among
      participants in the San Francisco Men's Health Study (SFMHS), which represents a
      geographically, temporally, and demographically defined subset of HIV-1
      infections in the United States. DNA was extracted from primary PBMCs obtained
      within 6 months of seroconversion and from individuals whose HIV-1 infection
      occurred between 1985 and 1989. The full-length envelope gene was PCR amplified,
      cloned, and sequenced from 17 different individuals. The sequences were compared
      within the cohort and with reference sequences from the United States and
      overseas, and their relationship to vaccine prototype strains LAI, MN, and SF2
      was evaluated. SFMHS participants harbored HIV-1 subtype B infections with
      limited interpatient variation and a higher proportion of atypical V3 loop crown
      sequences than reference sequences of this subtype. Throughout gp160, the MN
      strain was less representative than LAI or SF2 among the patients examined. The
      geographic component of variation was apparently more substantial than the
      temporal, emphasizing the need for widely distributed geographic sampling in
      estimations of HIV diversity.

PMID- 9519896
TI  - Differences in reverse transcriptase activity versus p24 antigen detection in
      cell culture, when comparing a homogeneous group of HIV type 1 subtype B viruses
      with a heterogeneous group of divergent strains.
AB  - Failure to detect infection with HIV-1 non-B subtypes in some antibody screening
      assays has been shown. To date, however, no studies have been published
      evaluating the capacity of standard tests to quantify replication of divergent
      HIV-1 in cell culture. Reverse transcriptase (RT) activity and p24 antigen assays
      are the two methods most commonly used for this purpose. A homogeneous panel of
      HIV-1 subtype B viruses from northern Italy and a heterogeneous panel of diverse
      genetic subtypes (A to F and O) from different regions of the world were cultured
      under identical conditions. A new nonradioactive RT assay was used as a basis for
      comparison to evaluate the capacity of two p24 assays to quantify viral growth in
      both panels. Comparison of the p24 amount/RT activity (p24/RT) ratios showed that
      ratios in the subtype B panel tended to be markedly higher than in the diverse
      subtype panel. Greatest variation was seen with one of the subtype O isolates,
      where up to a 400 times lower ratio was obtained compared with the average ratio
      for the subtype B panel. In addition, one Thai subtype B virus also gave a
      markedly reduced ratio. Furthermore, comparison between the two p24 assays showed
      different abilities to detect p24 from different HIV-1 isolates. We discuss
      limitations for the use of anti-HIV-1 p24 antibodies produced by immunization
      with subtype B p24 in p24 assays.

PMID- 9519897
TI  - Secretion of extracellular factor(s) induced by X-irradiation activates the HIV
      type 1 long terminal repeat through its kappaB motif.
AB  - X-irradiation has been used in the treatment of several human diseases, including
      AIDS-related-malignancies. X-irradiation might induce the transcription and the
      replication of human immunodeficiency virus type 1 (HIV-1) and enhance nuclear
      factor kappa B (NF-kappaB). In the present article we show that the activation of
      the HIV-1 long terminal repeat (LTR) by direct X-irradiation can be mimicked by
      coculture of transfected cells with X-irradiated nontransfected (HIV-1-negative)
      cells. In the human colonic carcinoma cell line HT29, the activation seems to
      depend on an extracellular factor(s) released by a cell line treated with X-rays.
      The HIV-1 LTR cis-acting element conferring X-indirect responsiveness was
      identified as the kappaB tandem motif. The two main nuclear HIV-1 kappaB-binding
      complexes activated by X-direct and -indirect irradiation were the NF-kappaB
      p50/p65 and c-Rel/p65 heterodimers. Nuclear NF-kappaB activation was dependent on
      protein neosynthesis. It was partially inhibited by 100 microM pyrrolidine
      dithiocarbamate, a potent antioxidant drug, but was not correlated with a
      significant decrease in cellular IkappaBalpha. Furthermore, X-irradiation induces
      the expression of several cytokine genes generally associated with stress
      response and antibodies against interleukin 6 and TNF-alpha partially inhibited
      the X-indirect activation of the HIV-1 LTR. The use of protein kinase C (PKC)
      specific inhibitor and of forskolin, an adenylate cyclase activator, suggests
      that a PKC-dependent pathway and the cAMP intracellular concentration could play
      a role in the X-indirect enhancement of HIV-1 LTR transcription in the HT29 cell
      line. In addition, supernatants of an X-irradiated HT29 cell culture activated
      the HIV-1 stimulation in infected peripheral blood monocytes.

PMID- 9519898
TI  - Simian T cell leukemia virus type I-induced malignant adult T cell leukemia-like
      disease in a naturally infected African green monkey: implication of CD8+ T cell
      leukemia.
AB  - Spontaneous T cell leukemia was found in an African green monkey (Cercopithecus
      aethiops, AGM) naturally infected with simian T cell leukemia virus type I (STLV
      I). The hematological features and the evidence for monoclonal integration of
      provirus DNA in the leukemic cells revealed that the leukemia was an ATL-like
      disease. The expression of surface markers on the leukemic cells indicated that
      they were defined as an activated CD8+ T cell subset. Together with the finding
      that seven in vitro spontaneously STLV-I-transformed cell lines were CD4-CD8+, it
      is likely that CD8+ T cells are transformed by STLV-I in AGMs, in contrast with
      human ATL. Finally, we assessed characteristics of the CD8 chains on these
      transformed cells. The result indicated that the leukemic cells expressed only
      the alpha chains but not the beta chains. However, in the case of in vitro
      transformed cell lines the expression pattern of the CD8 chains varied in
      individual monkeys. Thus, STLV-I may preferentially transform CD8+ (both
      alphaalpha+ and alphabeta+) T cells in AGMs.

PMID- 9519899
TI  - Myosin-carbohydrate interactions.

PMID- 9519900
TI  - Yeast myosin II: a new subclass of unconventional conventional myosins?
AB  - Myosin II is the founder member of a large and structurally diverse clan of actin
      based motor proteins. The native myosin II molecule is a hexamer consisting of
      two heavy chains, two essential light chains (ELC), and two regulatory light
      chains (RLC). For convenience, the myosin IIs are often subdivided into four
      subclasses: vertebrate skeletal and cardiac muscle myosin II form one subclass,
      vertebrate smooth muscle and nonmuscle myosin II a second, invertebrate muscle a
      third, and protozoan myosin II a fourth [Sellers and Goodson, 1995]. Different
      mechanisms of regulation may exist between myosins within a single subclass yet
      all myosin IIs share a common three-domain structure; the N-terminus of the heavy
      chain forms two globular heads that contain the ATP- and actin-binding sites and
      the alpha-helical neck region that is stabilised by the binding of the two
      classes of light chains, whilst the C-terminus forms an extended coiled-coil tail
      that can consist of anywhere between 700 and 1,200 amino acids. In nonmuscle
      cells, myosin II has at least two well-defined functions, cell locomotion and
      cytokinesis. Yeast cells do not locomote, and their mechanism of cytokinesis
      involves the deposition of a cross-wall or septum. However, in the fission yeast,
      Schizosaccharomyces pombe, deposition of the septum is anticipated by the
      appearance of a contractile actomyosin ring [Marks and Hyams, 1985; May et al.,
      1997; Kitayama et al., 1997] and actin is also present at the bud neck during
      cytokinesis in the budding yeast, Saccharomyces cerevisiae [Kilmartin and Adams,
      1984]. Here we report a phylogenetic analysis of the N-terminal head domains of
      the myosin IIs from both yeasts, a structural analysis of the tail domains of
      these proteins and we speculate as to the nature of the light chains that
      regulate their function. On the basis of these findings, we propose that the
      yeast myosin IIs constitute a divergent fifth class of "unconventional"
      conventional myosins.

PMID- 9519901
TI  - Activation of inositol 1,4,5-trisphosphate receptors induces transient changes in
      cell shape of fertilized Xenopus eggs.
AB  - Injection of inositol 1,4,5-trisphosphate (InsP3) into fertilized Xenopus eggs
      induced transient changes in cell shape. The region around the injected site
      contracted during the first 2 min, followed by swelling. These changes which
      initiated at the injected site extended toward the opposite side. Injection of
      adenophostin B, a potent InsP3 receptor agonist, also induced similar
      morphological changes, which suggested that InsP3 receptor activation, and not
      the action of InsP3 metabolites, is responsible for these changes. To determine
      whether these changes correlate to InsP3 receptor-mediated calcium release, we
      examined the morphological changes and those in intracellular free calcium
      concentrations ([Ca2+]i). A calcium wave was observed to precede the propagation
      of changes in cell shape by about 2 min. The extent of propagation of cell shape
      changes varied with the eggs but consistently depended on the extent of the
      calcium wave propagation. Changes in cell shape were inhibited in eggs injected
      with the calcium chelator, BAPTA, indicating that calcium released from the InsP3
      sensitive calcium store is required for cell shape changes. During the cell shape
      changes, the contracted region was strongly stained with rhodamine-phalloidin,
      which suggests that structural changes of actin filaments are involved in the
      cortical changes. We propose that spatiotemporally controlled elevation of
      intracellular calcium induces successive cortical cytoskeletal changes that are
      responsible for changes in cell shape. These observations provide insight into
      the potency of InsP3/calcium signaling in the regulation of cortical
      cytoskeleton.

PMID- 9519902
TI  - The ankyrin-binding domain of CD44s is involved in regulating hyaluronic acid
      mediated functions and prostate tumor cell transformation.
AB  - CD44 isoforms, such as CD44s (the standard form), contain at least one ankyrin
      binding site within the 70-amino acid (aa) cytoplasmic domain and several
      hyaluronic acid (HA)-binding sites within the extracellular domain. To study the
      role of CD44s-ankyrin interaction in regulating human prostate tumor cells, we
      have constructed several CD44s cytoplasmic deletion mutants that lack the ankyrin
      binding site(s). These truncated cDNAs were stably transfected into CD44-negative
      human prostate tumor cells (LNCaP). Our results indicate that a critical region
      of 15-amino acids (aa) between aa 304 and aa 318 of CD44s is required for ankyrin
      binding. Biochemical analyses, using competition binding assays with a synthetic
      peptide containing the 15 aa between aa 304 and aa 318 (NSGNGAVEDRKPSGL), further
      support the conclusion that this region contains the ankyrin-binding domain of
      CD44s. Deletion of this 15-aa ankyrin-binding sequence from CD44s results in a
      drastic reduction of HA-mediated binding/cell adhesion, Src p60 kinase(s)
      interaction and anchorage-independent growth in soft agar. These findings suggest
      that the binding of cytoskeletal proteins, such as ankyrin, to the cytoplasmic
      domain of CD44s plays a pivotal role in regulating HA-mediated functions as well
      as Src kinase activity and prostate tumor cell transformation.

PMID- 9519903
TI  - Glutamylation of centriole and cytoplasmic tubulin in proliferating non-neuronal
      cells.
AB  - We have examined the distribution of glutamylated tubulin in non-neuronal cell
      lines. A major part of centriole tubulin is highly modified on both the alpha-
      and beta-tubulin subunits, whereas a minor part of the cytoplasmic tubulin is
      slightly modified, on the beta-tubulin only. Furthermore, we observed that
      tubulin glutamylation varies during the cell cycle: an increase occurs during
      mitosis on both centriole and spindle microtubules. In the spindle, this increase
      appears more obvious on the pole-to-pole and kinetochore microtubules than on the
      astral microtubules. The cellular pattern and the temporal variation of this post
      translational modification contrast with other previously described tubulin
      modifications. The functional significance of this distribution is discussed.

PMID- 9519904
TI  - Studies on the eel sperm flagellum. 2. The kinematics of normal motility.
AB  - The sperm flagellum of Anguilla anguilla lacks outer dynein arms, radial spokes
      and central structures. Its characteristic motion has been obtained by studying
      cells swimming perpendicularly against, but not adhering to, the coverslip. The
      flagellum generates a sinistrally helical wave of rising, then falling,
      amplitude. The frequency of the wave, which can exceed 70 Hz, is inversely
      related to its maximum amplitude. As a reaction to the torque, the entire cell
      rolls (spins) in the opposite direction to that taken by points on the flagellum
      in the generation of the sinistral wave. However, because the head (which
      contributes on opposing torque) is asymmetrical, the axis of this counter
      rotation is displaced laterally from the axis of the flagellar rotation. As a
      result, the flagellum precesses around the progression axis, with each point on
      the flagellum travelling along a special flagelloid curve, specified by the
      ratios of the two frequencies and the two radii for the circular motions. The
      instantaneous flagellar waveform (the flagelloid wave) is thus derived as a
      succession of phase-shifted points on the series of flagelloid curves along the
      axis of the cell's rotation. This adds complexity to the underlying, rather
      simple, helical geometry. Calculations suggest that the forward swimming speed of
      the sperm is greatly aided by the orientation and shape of the sperm head. The
      movement of latex beads was observed around sperm swimming against the coverslip
      and around sperm swimming freely. Bulk, vortical flows of fluid were seen in the
      former case and net lateral displacements in the latter; this is in accordance
      with hydrodynamic theory for low Reynolds number systems.

PMID- 9519905
TI  - Studies on the eel sperm flagellum. 3. Vibratile motility and rotatory bending.
AB  - A further account is given of motility in this 9 + 0 flagellum, where the axoneme
      is of special interest because it is powered by only inner dynein arms. Under
      some circumstances, normal motility is inactivated and yet the flagellum swims
      (or appears to glide) forward, albeit much more slowly. The propulsive thrust in
      these cases is due to a vibratile motion of the flagellum. Vibratile motion has a
      very small amplitude and is very rapid, but a frequency could not be determined
      stroboscopically. Provided that the sperm head is in place, a vibratile sperm can
      be stimulated mechanically such that it instantly resumes and continues normal
      motility. This indicates that a suprathreshold deformation of the axoneme
      triggers normal motility and that the threshold is normally continuously exceeded
      by a self-generated fluid-mechanical interaction in which the sperm head plays a
      necessary part. Without a sperm head, the flagellum propels itself by vibratile
      motion. Some vibratile sperm, found to be stuck by their heads, perform also a
      slow rotatory (clockwise) bending at the base of the flagellum. When this
      happens, there is no rotation of the axonemal substance. Therefore, this is
      interpreted as sequential, clockwise, self-perpetuating, circumferential activity
      around the arrays of inner dynein arms. The phenomenon is considered to be a
      restricted representation of the rapid clockwise (i.e., sinistral) helical wave
      of normal motility.

PMID- 9519906
TI  - Use of ampicillin/sulbactam (sultamicillin) in the management of pediatric
      infections. Introduction.

PMID- 9519907
TI  - Beta-lactam antibiotics: their role in the management of infections in children.

PMID- 9519908
TI  - Beta-lactamase production and the role of ampicillin/sulbactam.

PMID- 9519909
TI  - Clinical use of sultamicillin (ampicillin/sulbactam) in children.

PMID- 9519913
TI  - A response to missed appointments and Medicaid managed care.

PMID- 9519910
TI  - Comparison of ampicillin/sulbactam plus aminoglycoside vs. ampicillin plus
      clindamycin plus aminoglycoside in the treatment of intraabdominal infections in
      children. The Multicenter Group.

PMID- 9519914
TI  - Religious commitment and health status: a review of the research and implications
      for family medicine.
AB  - The empirical literature from epidemiological and clinical studies regarding the
      relationship between religious factors (eg, frequency of religious attendance,
      private religious involvement, and relying on one's religious beliefs as a source
      of strength and coping) and physical and mental health status in the areas of
      prevention, coping, and recovery was reviewed. Empirical studies from the
      published literature that contained at least 1 measure of subjects' religious
      commitment and at least 1 measure of their physical or mental health status were
      used. In particular, studies that examined the role of religious commitment or
      religious involvement in the prevention of illness, coping with illnesses that
      have already arisen, and recovery from illness were highlighted. A large
      proportion of published empirical data suggest that religious commitment may play
      a beneficial role in preventing mental and physical illness, improving how people
      cope with mental and physical illness, and facilitating recovery from illness.
      However, much still remains to be investigated with improved studies that are
      specially designed to investigate the connection between religious involvement
      and health status. Nevertheless, the available data suggest that practitioners
      who make several small changes in how patients' religious commitments are
      broached in clinical practice may enhance health care outcomes.

PMID- 9519916
TI  - Use of the intrauterine device by inner-city women.
AB  - OBJECTIVE: To examine the use, effectiveness, acceptability, and continuation
      rates of the copper T 380 A intrauterine device (IUD) among women attending an
      inner-city family planning clinic. DESIGN: A 1-year prospective cohort study.
      SETTING: The family planning clinic of Grady Memorial Hospital, which serves the
      inner-city indigent population of Fulton and Dekalb counties in metropolitan
      Atlanta, Ga. PARTICIPANTS: A total of 115 women with 1 or more live births who
      were in a mutually monogamous relationship for the previous year had the copper T
      380 A IUD inserted between December 20, 1990, and June 28, 1991. MAIN OUTCOME
      MEASURES: Follow-up, consisting of history and a pelvic examination, was done 2,
      6, and 12 months after IUD insertion to determine the status of the IUD and to
      detect any complications related to its use. At the end of the study, the
      continuation rates, reasons for removal, and complications related to IUD use
      were assessed. RESULTS: Thirty-seven women were unavailable for follow-up. Eight
      of those were seen in other clinics at Grady Memorial Hospital, but no mention
      was made of their IUD status. Fifty-six of the remaining 78 women were known to
      continue IUD use without any complications at the end of the 12 months. Among the
      22 women known to have the IUD removed, 8 women cited no problems. Pelvic pain,
      menometrorrhagia, desire for permanent sterilization, and expulsion of the device
      were mentioned as reasons for other IUD removals. Pelvic inflammatory disease was
      not documented in any of the patients during the year of follow-up. CONCLUSION:
      With proper screening and counseling, the IUD may be used successfully in
      selected patients in inner-city family planning clinics.

PMID- 9519915
TI  - Personality disorders among difficult patients.
AB  - OBJECTIVE: To determine the association between "difficult" patient status and
      personality disorder. DESIGN: A survey using the Diagnostic Interview for
      Personality Disorders. PARTICIPANTS: Twenty-one patients nominated by 9 family
      medicine providers who subjectively experienced their care as difficult and 22
      control subjects systematically selected from the same practices. MAIN OUTCOME
      MEASURE: The presence of personality disorder measured by the Diagnostic
      Interview for Personality Disorders. RESULTS: Personality disorders were more
      prevalent among the difficult patients: 7 of 21 difficult patients and 1 of 22
      control subjects had at least 1 personality disorder (P = .02). Five of 7
      difficult patients had dependent personality disorder. None of the providers
      realized that the difficult patients had personality disorders. CONCLUSIONS:
      Unrecognized personality disorder can make difficult provider-patient
      relationships more likely. Dependent personality disorder may be especially
      difficult. Improved physician awareness of personality disorders may lead to more
      effective understanding and treatment of some difficult patients.

PMID- 9519917
TI  - Physician self-report of comfort and skill in providing preventive care to
      patients of the opposite sex.
AB  - BACKGROUND: Cancer screening in adults is a fundamental responsibility of primary
      care physicians. Previous studies have reported that when the patient and the
      physician are of the same sex, screening rates are higher; previous studies have
      also reported that trainees believe that they are poorly prepared for and are
      uncomfortable while performing sex-sensitive examinations. OBJECTIVES: To compare
      the level of skill and comfort of male physicians with that of female physicians
      in conducting breast and prostate examinations, obtaining Papanicolaou smears,
      and obtaining a sexual history from men and women and to compare ratings of
      comfort and skill of internists with those of family physicians. METHODS: We
      surveyed 389 internists and family physicians from a large health plan in
      Minnesota. All female physicians and a random sample of male physicians were
      surveyed. Respondents rated their level of skill and comfort in conducting breast
      and prostate examinations, obtaining Papanicolaou smears, and obtaining a sexual
      history from a man and a woman. We compared the responses of male and female
      internists with those of male and female family physicians and computed odds
      ratios (ORs), adjusting for physician age and specialty. We also compared the
      ratings of comfort and skill of internists with those of family physicians.
      RESULTS: Compared with male physicians, female physicians were more likely to
      report being "very comfortable" performing breast examinations (OR, 7.55; 95%
      confidence interval [CI], 3.06-18.65), obtaining Papanicolaou smears (OR, 13.80;
      95% CI, 3.16-60.20), and obtaining sexual histories from women (OR, 3.99; 95% CI,
      2.33-6.84). Conversely, female physicians were less likely to report being very
      comfortable obtaining sexual histories from men (OR, 0.52; 95% CI, 0.33-0.82).
      Only 6% and 13% of female family physicians and internists, respectively,
      believed that their skill in performing a prostate examination was excellent
      compared with 49% and 37% of male family physicians and internists, respectively
      (OR, 0.12; 95% CI, 0.06-0.22). CONCLUSIONS: Internal medicine and family practice
      physicians report significantly less comfort and lower levels of skill when
      performing sex-related examinations or obtaining a sexual history from patients
      of the opposite sex. Interventions to improve skill and comfort level should be
      considered.

PMID- 9519919
TI  - Treating depression: talking among the disciplines.

PMID- 9519918
TI  - Management of patients with depression by rural primary care practitioners.
AB  - OBJECTIVE: To investigate the extent to which variations in treatment and
      referral patterns for adult patients with diagnosed symptoms of depression seen
      in primary care practices are explained by practitioner characteristics, such as
      training, years in primary practice, sex, and knowledge about depression;
      practice characteristics, such as size, patient volume, and payer mix; and
      service area characteristics, such as availability of specialty mental health
      services and rural location. DESIGN: A 41-item telephone survey of primary care
      practitioners (PCPs) in Maine, including family and general practice doctors of
      medicine and doctors of osteopathy, general internists, nurse practitioners, and
      physician assistants (n = 267). MAIN OUTCOME MEASURE: The degree to which PCPs
      treat patients with depression themselves, rather than refer them to a mental
      health specialist. RESULTS: There is no significant (P = .10) urban-rural
      difference in the number of patients with depression seen as a percentage of
      total patient volume. Major barriers to referral to a mental health provider, as
      reported by the PCP, are long wait for an appointment, lack of available
      services, patients' unwillingness to use services, and reimbursement issues.
      Multivariate analyses indicate that PCP characteristics measuring knowledge and
      attitudes, as well as the lack of available services, are significantly related
      to treatment and referral patterns while practice characteristics and mental
      health provider supply are not. CONCLUSION: The treatment of rural patients with
      symptoms of depression is more likely to be improved by targeting PCPs' medical
      education than by efforts to increase the supply of specialty mental health
      providers in rural areas.

PMID- 9519920
TI  - How students learn from community-based preceptors.
AB  - OBJECTIVE: To explore how students learn in community-based family physicians'
      offices from the student's point of view. METHOD: Each student completing a
      community-based family medicine clerkship wrote a "critical incident" narrative
      about an event that was particularly educational. A coding system was developed
      by a multidisciplinary research team and thematic analysis was conducted.
      RESULTS: Critical education experiences were brief, problem-focused, had
      definitive outcomes, were often collaborative, and led to self-reflection. The
      most commonly identified mode of learning was "active observation." In most of
      these situations, the student had significant clinical responsibility, but some
      involved observation of complex tasks beyond the expectations of a medical
      student. Most (77%) identified their learning needs after having observed a
      preceptor, rather than prospectively. Collaboration, coaching, advocacy, and
      exploring affect were means whereby preceptors and students created a learning
      environment that students felt was safe, allowed them to recognize their own
      learning needs, and helped them adopt new behaviors. CONCLUSIONS: These findings
      broaden the definition of active learning to include active observation and
      support learner-centered and relational models of learning. Increasing
      preceptors' awareness of these modes of student learning will enhance the quality
      of education in ambulatory settings.

PMID- 9519921
TI  - The effect of glycemic control on the incidence of macrovascular complications of
      type 2 diabetes.
AB  - Of all the complications of diabetes mellitus, macrovascular complications, ie,
      large-vessel atherosclerosis, account for the largest share of morbidity,
      mortality, and health care expenditures. Whereas there is now highly persuasive
      evidence that glycemic control reduces the risk of microvascular complications in
      type 1 diabetes, and probably in type 2 diabetes as well, such evidence is
      unavailable for macrovascular complications. Prospective epidemiologic studies,
      however, indicate that poor glycemic control enhances cardiovascular risk, and a
      number of biochemical mechanisms have been advanced to explain this phenomenon.
      However, data from animal studies, in vitro studies, and prospective
      epidemiologic studies suggest that endogenous insulin or insulin resistance may
      be atherogenic. Thus, a dilemma exists for insulin treatment, although the weight
      of evidence still favors its aggressive use. For persons whose glycemia can be
      adequately controlled with oral agents, the use of agents such as metformin and
      troglitazone--which do not raise, and may even lower, insulin concentrations--may
      offer an advantage. Definitive clinical trials on the benefits and risks of
      insulin therapy related to macrovascular complications are lacking and urgently
      needed.

PMID- 9519922
TI  - Preoperative cardiac evaluation for elective noncardiac surgery.
AB  - We reviewed the approach to preoperative cardiac risk assessment, incorporating
      new information regarding the pathophysiologic features of perioperative
      myocardial ischemia and recent clinical trials. Relevant articles were identified
      from a MEDLINE search, followed by bibliography review of the articles
      identified. The multifactorial risk indexes are valuable in stratifying risks
      among unselected patients undergoing noncardiac surgery, but they underestimate
      the risks in selected groups, particularly patients with peripheral vascular
      disease. The preoperative evaluation of patients with coronary artery disease and
      risk reduction strategies for high-risk patients are considered. There are no
      prospective randomized clinical data comparing preoperative revascularization to
      intensive medical therapy and clinical decisions must be individualized. Risks
      particular to patients with congestive heart failure and valvular heart disease
      are also reviewed. Patients with congestive heart failure can undergo noncardiac
      surgery safely, if their cardiac disease is well-compensated. Patients with
      aortic stenosis have high risks, and management strategies include valve
      replacement, aortic valvuloplasty, and aggressive medical treatment. These
      modalities have not been compared prospectively, and clinical decisions must be
      individualized. Preoperative arrhythmias are important risk factors, although
      they appear to confer risk only when due to underlying heart disease. A thorough,
      targeted history and physical examination supplemented with judicious laboratory
      studies are usually sufficient to assess a patient's risk for upcoming noncardiac
      surgery. The clinical history should identify risk factors that predict cardiac
      complications, and special attention should be given to those risk factors that
      can be modified before surgery. New developments in perioperative medicine will
      likely lead to postoperative interventions to reduce silent myocardial ischemia
      and clinical complications.

PMID- 9519923
TI  - A field trial of 2 telemedicine camera systems in a family practice.
AB  - Previous reports of telemedicine consultations have demonstrated that the
      technology is effective but inefficient. Little attention has been directed to
      the use of telemedicine in a primary care practice, especially the use of the
      medical peripheral devices. We used a functioning primary care practice as a
      telemedicine test bed, providing unselected patients in the study group. The goal
      was to study the performance of a new generation of a compact set of medical
      peripheral devices specifically designed for telemedicine examinations. In a 3
      week field trial, 2 second-generation camera systems were used by physician
      faculty and residents in family practice to examine the skin, ears, and pharynx
      of 34 patients, ranging in age from 10 months to 78 years. Evaluations by the
      clinicians and patients were obtained. The average duration of an examination
      using these systems was 2 minutes. Patients' response was uniformly positive. A
      "pistol grip" video otoscope obtained an acceptable image, unless canal debris
      obscured the view. The system that provided pneumatic otoscopy was preferred,
      with some modifications necessary to obtain an airtight seal. The preferred skin
      camera was one that provided an image of a size that clinicians were most
      accustomed to viewing, although stability of this handheld camera was a problem.
      This camera also worked well to visualize the pharynx, especially in children
      with symptoms of pharyngitis. Color was deemed important in all 3 anatomical
      areas, and using auto-white balance and excluding fluorescent lights were
      preferred. Thus, the second-generation telemedicine peripheral devices were
      effective for use in a group of unselected primary care patients. These camera
      systems can be used by nursing personnel and require a minimum of time per
      examination.

PMID- 9519924
TI  - Overwhelming postsplenectomy infection in a patient with penicillin-resistant
      Streptococcus pneumoniae.
AB  - Overwhelming postsplenectomy infection is a fulminant process that carries a poor
      prognosis. Streptococcus pneumoniae is the most likely organism to cause disease.
      Infection with penicillin-resistant S pneumoniae is increasing; its prevalence
      ranges from 6.6% to 50% in the United States. If meningeal involvement with
      resistant pneumococcus is suspected, it should be treated with a third-generation
      cephalosporin and vancomycin hydrochloride. The long-term management of asplenic
      patients should focus on preventing infection. The current guidelines and
      recommendations for vaccination are reviewed. Educating these patients to contact
      their physician at the first sign of minor illness is also beneficial. The use of
      antibiotic prophylaxis remains a controversy and is best left to the discretion
      of the physician.

PMID- 9519926
TI  - Ethical issues in lung transplantation.
AB  - Lung transplantation is now an accepted therapeutic option for many patients with
      incurable end-stage lung or pulmonary vascular disease processes for which other
      treatment options have been expended. However, as lung transplantation has
      evolved as a recognized discipline over the past decade, a variety of ethical
      issues related to the transplant process are emerging. This article considers
      those issues through a discussion of the four fundamental principles of
      biomedical ethics.

PMID- 9519925
TI  - Use of Native American healers among Native American patients in an urban Native
      American health center.
AB  - To gain an understanding of the prevalence, utilization patterns, and practice
      implications of the use of Native American healers together with the use of
      physicians, we conducted semistructured interviews at an urban Indian Health
      Service clinic in Milwaukee, Wisc, of a convenience sample of 150 patients at
      least 18 years old. The mean age of patients was 40 years, and the sex
      distribution was 68.7% women and 31.3% men. Thirty tribal affiliations were
      represented, the largest groups being Ojibwa (20.7%), Oneida (20.0%), Chippewa
      (11.3%), and Menominee (8.0%). We measured the number of patients seeing healers
      and gathered information on the types of healers, the ceremonies used for
      healing, the reasons for seeing healers, and whether patients discuss with their
      physicians their use of healers. We found that 38.0% of the patients see a
      healer, and of those who do not, 86.0% would consider seeing one in the future.
      Most patients report seeing a healer for spiritual reasons. The most frequently
      visited healers were herbalists, spiritual healers, and medicine men. Sweat lodge
      ceremonies, spiritual healing, and herbal remedies were the most common
      treatments. More than a third of the patients seeing healers received different
      advice from their physicians and healers. The patients rate their healer's advice
      higher than their physician's advice 61.4% of the time. Only 14.8% of the
      patients seeing healers tell their physician about their use. We conclude that
      physicians should be aware that their Native American patients may be using
      alternative forms of treatment, and they should open a respectful and culturally
      sensitive dialogue about this use with their patients.

PMID- 9519927
TI  - Lung transplantation for fibrotic lung diseases.
AB  - The underlying disease of a candidate for lung transplantation, especially
      advanced pulmonary fibrosis, can cause particular and dramatic difficulties.
      Pulmonary fibrosis is the end-result of a variety of pathological diseases and
      their associated processes. This article summarizes the diagnosis and management
      of some of the more common causes of fibrosis, outlines their natural histories
      and treatment outcomes, and describes the trade-off of pulmonary fibrosis for
      lung transplantation. Four main categories of end-stage fibrosis are discussed:
      idiopathic pulmonary fibrosis, sarcoidosis, pulmonary fibrosis from systemic
      diseases or drugs, and occupational- or environmental-related pulmonary fibrosis.
      Each group will be covered systematically and the options and indications for
      lung transplantation will be addressed.

PMID- 9519928
TI  - Cystic fibrosis: bilateral living lobar versus cadaveric lung transplantation.
AB  - Living donor transplantation is now an acceptable option that should be
      considered for selected cystic fibrosis patients with end-stage lung disease. Two
      lungs obtained from live donors can adequately support an adult cystic fibrosis
      patient. The morbidity from lobectomy to the healthy donor is minimal.

PMID- 9519929
TI  - Bronchiolitis obliterans: pathogenesis, prevention, and management.
AB  - Increasing early success-post lung transplant has been tempered by the long-term
      development of histologic bronchiolitis obliterans (OB) or of the progressive
      airway obstruction which is called bronchiolitis obliterans syndrome (BOS).
      Multiple lines of evidence suggest that OB/BOS is due to an injury directed
      against the epithelial cells in the airways of the donor lung by the immune
      system of the recipient. Acute rejection is the strongest risk factor for the
      subsequent development of this process. Efforts to prevent or minimize acute
      rejection may reduce the prevalence of OB/BOS. Results of treatment with
      augmented immunosuppression have been disappointing but the treatment of
      complicating infections in the allograft can be beneficial. Multicenter studies
      are needed to assess the efficacy of new immunosuppressive agents in preventing
      or treating OB/BOS.

PMID- 9519930
TI  - Medical and surgical treatment options for pulmonary hypertension.
AB  - Significant advances in the treatment of pulmonary hypertension have been
      achieved in the past decade. Approximately one quarter of patients with primary
      pulmonary hypertension (PPH) can be effectively managed with chronic calcium
      channel blocker therapy; for the remainder, transplantation or continuous
      intravenous epoprostenol are complex but effective approaches. Epoprostenol
      therapy was initially envisioned as a bridge to transplantation, but recent
      experience has established this approach as an alternative to transplantation in
      some patients, with comparable survival rates. Not all patients derive benefit
      from epoprostenol, however, and adverse effects are common. Accordingly, patients
      who fall into New York Heart Association Functional Classes III and IV and who
      are refractory to oral vasodilator therapy should be evaluated both for the
      initiation of epoprostenol therapy and concurrent listing for transplantation. By
      delaying or avoiding transplantation through the use of epoprostenol, these
      patients may also benefit from ongoing research that targets novel therapeutic
      approaches and less cumbersome delivery mechanisms. Thus, epoprostenol may serve
      as a bridge to transplantation for some patients and to newer therapeutic options
      for others.

PMID- 9519931
TI  - Exercise-induced oxidative stress in patients during thallium stress testing.
AB  - BACKGROUND: Free radical injury is implicated in the pathogenesis of coronary
      artery disease, including atherogenesis and reperfusion/injury. Strenuous
      physical exercise can cause oxidative stress by several mechanisms, including
      reperfusion/injury. We hypothesize that exercise-induced lipid peroxidation is
      greater among those with than those without exercise induced myocardial ischemia.
      METHODS: The effect of physical exercise stress testing on plasma malonaldehyde
      (MDA) levels was compared between patients with (Group A, N = 8) and without
      (Group B) exercise-induced myocardial ischemia by thallium imaging. ANALYSIS: Two
      way ANOVA was used to compare plasma MDA levels pre- and post-exercise, and
      paired t-test comparisons were conducted for percent MDA changes between Group A
      and Group B patients. RESULTS: Two-way ANOVA revealed a significant (P = 0.002)
      directional difference in response to exercise between the groups' mean plasma
      MDA levels (Group A increased by 46 +/-12.7 percent, Group B decreased by 16.8+/
      4.6 percent). CONCLUSIONS: Differences in exercise-induced lipid peroxidation
      between patients with and without thallium documentation of myocardial ischemia
      have important implications in the development of clinical markers of coronary
      artery disease and further research related to atherogenesis.

PMID- 9519932
TI  - Predictors of lean body mass and total adipose mass in community-dwelling elderly
      men and women.
AB  - As part of an ongoing longitudinal study, we analyzed cross-sectional data to
      identify the predictors of lean body mass (LBM) and total adipose mass (TAM) in
      community-dwelling elderly men and women. Body composition analysis was done
      using dual energy x-ray absorptiometry. A total 262 subjects (118 women and 144
      men), 60 to 80 years of age, from the urban and suburban communities of
      southeastern Wisconsin were studied. In women, the age (r = -.18), body mass
      index (BMI) (r = .43), and waist-to-hip ratio (WHR) (r = .30), and in men, BMI (r
      = .45) and insulin-like growth factor-1 (IGF-1) (r = .32) were identified as
      predictors (P < .05) of LBM. In women, the BMI (r = .87), WHR (r = .21), and
      functional work capacity (VO2 max) (r = -.47), and in men, the BMI (r = .83), WHR
      (r = .52), dehydroepiandrosterone sulfate (DHEAS) (r = -.27), total testosterone
      (TT) (r = -.35), free testosterone (FT) (r = -.23), physical activity (LTE) (r = 
      .32), and VO2 peak (r = -.59) were identified as predictors of TAM. After
      partialling out age in addition to the predictors identified earlier, the VO2
      peak was identified as a predictor (P < .05) of LBM in both women and men, and
      TT, FT, and LTE as predictors (P < .05) of LBM in men. We conclude that the BMI,
      WHR, and VO2 peak influences LBM and TAM in both women and men. Additionally, in
      men LBM and TAM is influenced by hormone profile.

PMID- 9519933
TI  - Can a clinical score aid in early diagnosis and treatment of various stroke
      syndromes?
AB  - BACKGROUND: Accurate and timely diagnosis of hemorrhagic and nonhemorrhagic
      strokes helps in patient management. Neuroimaging studies are useful in diagnosis
      and distinction of hemorrhagic (HS) and nonhemorrhagic (NHS) strokes. The use of
      clinical variables, such as Siriraj stroke scores (SSS), has shown good
      sensitivity, specificity and predictive values (distinguishing stroke types). The
      aim of our study was to evaluate the use of SSS in a U.S. population and assess
      whether it could aid to expedite treatment decisions. METHODS: Levels of
      consciousness, vomiting, headache and atheroma markers used in SSS were applied
      to patients who met the criteria for stroke. RESULTS: Of the 302 patients
      identified, the SSS classified 254 with sensitivity of 36% (HS) and 90% (NHS) and
      positive predictive values of 77% and 61%, respectively. CONCLUSION: Our results
      suggest that SSS is not reliable in distinguishing stroke types (in a US
      population). Definite neuroimaging studies are needed prior to thrombolytic
      therapy.

PMID- 9519934
TI  - Elevated levels of erythropoietin in cerebrospinal fluid of depressed patients.
AB  - To investigate the role of erythropoietin (EPO) in the central nervous systems,
      we assayed EPO concentrations in the cerebrospinal fluid (CSF) of patients with
      depression or old cerebrovascular injuries and controls. Concentrations of EPO in
      the CSF were significantly higher in 13 patients with depression (3.21+/-0.46
      mU/mL) than in 10 patients with old cerebrovascular diseases (1.80+/-0.32 mU/mL,
      P < 0.01), and in 10 healthy controls (0.98+/-0.26 mU/mL, P < 0.01). Serum EPO
      concentrations did not differ among these three groups. In the patients with
      depression, 5 months of treatment with imipramine and/or nortriptyline
      significantly reduced EPO concentrations in the CSF (1.56+/-0.34 mU/ mL, P <
      0.01). Results suggest that the brain of patients with depression may be in an
      hypoxic state, and that the increased EPO in the CSF may act to limit hypoxia
      induced damage to neurons in these patients.

PMID- 9519935
TI  - Fatal leukoencephalopathy in a patient with non-Hodgkin's lymphoma treated with
      CHOP chemotherapy and high-dose steroids.
AB  - Leukoencephalopathy syndromes encompass a variety of neurologic abnormalities
      that affect cerebral white matter. Known etiologies include malignant
      hypertension, eclampsia, renal failure, CNS infection, and drug therapy with
      cyclosporine, tacrolimus (FK506) and interferon-alpha. Symptoms vary according to
      sites of involvement; they include altered mentation, visual disturbances, focal
      neurologic signs, and seizures. Characteristic radiologic findings are hypodense
      areas without contrast enhancement on CT and an increased T2 signal on MRI. The
      hypodense areas are often symmetric. The clinical symptoms and neuroimaging
      abnormalities are often reversible with treatment of the underlying condition or
      removal of the offending drug. We describe a patient with non-Hodgkin's lymphoma
      treated with conventional cyclophosphamide, doxorubicin, vincristine, and
      prednisone (CHOP) chemotherapy and high-dose steroids who developed a rapidly
      progressive fatal leukoencephalopathy. Her neurologic symptoms and findings on CT
      are consistent with reported cases of leukoencephalopathy; however, in this
      instance, the syndrome was not reversible and was ultimately fatal. None of the
      previously described etiologies could be demonstrated in association with the
      patient's illness. There are no prior reports of fatal leukoencephalopathy in
      adult patients treated with standard-dose CHOP. We believe the concurrent
      immunosuppression from chemotherapy and high-dose steroids resulted in this
      patient's fatal complication.

PMID- 9519936
TI  - Central nervous system involvement in patients with HCV-related cryoglobulinemia.
AB  - Central nervous system involvement was rarely described in patients with mixed
      cryoglobulinemia (MC). Most cases were reported before 1991, so these patients
      were not tested for hepatitis C virus (HCV) infection. However, two cases of
      cerebral ischemia in patients with HCV-related MC were recently reported. We
      describe three patients with chronic HCV and cryoglobulinemia, who complained of
      mild neurologic symptoms (dizziness, equilibrium impairment, monolateral
      hyposthenia, and defective sensitivity) which can be ascribed to central nervous
      system involvement. In all of these patients, brain magnetic resonance imaging
      showed multiple small hyperintensities compatible with ischemic lesions.

PMID- 9519937
TI  - Microangiopathic hemolytic anemia as a complication of diabetes mellitus.
AB  - A mature-onset diabetic patient who developed microangiopathic hemolytic anemia
      (MHA) is presented. Although numerous causes of hemolysis are reported in the
      literature, MHA is a rare complication of diabetes. The proposed mechanism of
      hemolytic anemia is thought to be related to the abnormal formation of cell
      membranes in the diabetic environment. The ratio of cholesterol to phospholipid
      in the core of the membrane is altered in diabetics; as a result, the red blood
      cell wall becomes rigid and nondeformable. The abnormal cells becomes disrupted
      as they circulate through the microangiopathic blood vessels. The mechanism of
      action of the antiplatelet agents is to enhance cell membrane compliance. With
      improved cell-wall compliance, one can expect a reduction in hemolysis, as
      occurred in our patient. The literature on diabetes mellitus-related
      microangiopathic hemolytic anemia is reviewed.

PMID- 9519938
TI  - Wegener's granulomatosis in a patient with apparent drug-induced acute
      interstitial nephritis.
AB  - We describe a patient whose clinical presentation was suggestive of drug-induced
      acute interstitial nephritis (AIN). A renal biopsy and serologic testing led
      instead to the diagnosis of Wegener's granulomatosis (WG) with necrotizing
      crescentic glomerulonephritis. Treatment with corticosteroids and
      cyclophosphamide resulted initially in complete recovery of renal function, and
      an exacerbation of acute renal failure after doses of these agents had been
      tapered responded to resumption of the original regimen. We report this case to
      emphasize the potentially identical presentations of AIN and WG. Since the two
      conditions are treated differently, we suggest that the diagnosis of AIN should
      be accepted only after biopsy confirmation.

PMID- 9519939
TI  - Neurosarcoidosis presenting as hypopituitarism and a cystic pituitary mass.
AB  - We report a young woman with clinical hypopituitarism and systemic sarcoidosis
      involving the lung, gastrointestinal tract, and peripheral lymph nodes.
      Laboratory evaluation confirmed that cortisol, thyroid indices, insulin-like
      growth factor 1, follicle-stimulating hormone, luteinizing hormone, and estradiol
      levels were low, with a normal prolactin. Magnetic resonance imaging revealed a
      large cystic pituitary lesion compressing the optic chiasm and exhibiting rim but
      not hypothalamic enhancement. The differential diagnosis included cystic
      macroadenoma, Rathke's cleft cyst, craniopharyngioma, and simple cyst. A
      transsphenoidal procedure provided decompression and diagnosis: pathology was
      consistent with sarcoidosis. Postoperatively, the patient's neurosarcoid disease
      markedly worsened, requiring hypothalamic irradiation. To our knowledge, this is
      the first report of intracranial sarcoidosis presenting solely as a cystic
      pituitary mass. An awareness of this possibility is important to prevent
      inappropriate neurosurgical intervention and subsequent potential exacerbation of
      neurosarcoidosis.

PMID- 9519940
TI  - Aboriginal health, a missing dimension.

PMID- 9519941
TI  - Inhaled steroids in COPD.

PMID- 9519942
TI  - Ankylosing spondylitis, HLA B27, and beyond.

PMID- 9519943
TI  - Assessment of dementia.

PMID- 9519944
TI  - Rise in prevalence of hypospadias.

PMID- 9519945
TI  - Hydroxychloroquine and retinal safety.

PMID- 9519946
TI  - Changing attitudes to disability in hospitals.

PMID- 9519947
TI  - Public's perception of RCTs.

PMID- 9519948
TI  - Multicentre randomised placebo-controlled trial of inhaled fluticasone propionate
      in patients with chronic obstructive pulmonary disease. International COPD Study
      Group.
AB  - BACKGROUND: The efficacy of inhaled corticosteroids in the treatment of chronic
      obstructive pulmonary disease (COPD) remains controversial because of a lack of
      placebo-controlled studies. We compared the effect of inhaled fluticasone
      propionate with placebo in the treatment of patients with COPD. METHODS: We used
      a randomised, double-blind, placebo-controlled design. We enrolled from 13
      European countries, New Zealand, and South Africa, 281 outpatient current or ex
      smokers, aged between 50 and 75 years. They had a forced expiratory volume in 1 s
      (FEV1) of between 35% and 90% of predicted normal values, a ratio of FEV1 to
      forced vital capacity of 70% or less and bronchodilator reversibility of less
      than 15%, as well as a history of chronic bronchitis. Patients were randomly
      assigned fluticasone propionate 500 microg (n=142) or placebo (n=139) twice daily
      via a metered-dose inhaler for 6 months. The main outcome measures were the
      number of patients who had at least one exacerbation by the end of treatment, the
      number and severity of exacerbations, clinic lung function, diary card symptoms
      and peak expiratory flow and 6 min walking distance. FINDINGS: 51 (37%) patients
      in the placebo group compared with 45 (32%) in the fluticasone propionate group
      had had at least one exacerbation by the end of treatment (p=0.449).
      Significantly more patients had moderate or severe exacerbations in the placebo
      group than in the fluticasone propionate group (86% vs 60%, p<0.001). Diary-card
      and clinic morning peak expiratory flows improved significantly in the
      fluticasone propionate group (p<0.001, p=0.048, respectively), as did clinic FEV1
      (p<0.001), forced vital capacity (p<0.001), and mid-expiratory flow (p=0.01).
      Symptom scores for median daily cough and sputum volume were significantly lower
      with fluticasone propionate treatment than with placebo (p=0.004 and p=0.016,
      respectively). At the end of treatment, patients on fluticasone propionate had
      increased their 6 min walking distance significantly more than those on placebo
      (p=0.032). Fluticasone propionate was tolerated as well as placebo, with few
      adverse effects and without a clinically important effect on mean serum cortisol
      concentration. INTERPRETATION: Fluticasone propionate may be of clinical benefit
      in patients with COPD over at least 6 months. Inhaled corticosteroids may have an
      important role in the long-term treatment of COPD.

PMID- 9519949
TI  - Dietary sodium intake and mortality: the National Health and Nutrition
      Examination Survey (NHANES I).
AB  - BACKGROUND: Population-wide restriction of dietary sodium has been recommended.
      However, little evidence directly links sodium intake to morbidity and mortality.
      The aim of this study was to assess the relation of sodium intake to subsequent
      all-cause and cardiovascular-disease (CVD) mortality in a general population.
      METHODS: The first National Health and Nutrition Examination Survey established
      baseline information during 1971-75 in a representative sample of 20729 US adults
      (aged 25-75). 11348 underwent medical examination and nutritional examination
      based on 24 h recall. Two had no data on sodium intake available. Vital status at
      June 30, 1992, was obtained for the 11346 participants through interview,
      tracing, and searches of the national death index. Mortality was examined in sex
      specific quartiles of sodium intake, calorie intake, and sodium/calorie ratio.
      Multiple regression analyses were done to assess the relations with mortality.
      FINDINGS: There were 3923 deaths, of which 1970 were due to CVD. All-cause
      mortality (per 1000 person-years; adjusted for age and sex) was inversely
      associated with sex-specific quartiles of sodium intake (lowest to highest
      quartile 23.18 to 19.01, p<0.0001) and total calorie intake (25.03 to 18.40,
      p<0.0001) and showed a weak positive association with quartiles of sodium/calorie
      ratio (20.27 to 21.71, p=0.14). The pattern for CVD mortality was similar (sodium
      11.80 to 9.60, p<0.0019; calories 12.80 to 8.94, p<0.0002; sodium/calorie ratio
      9.73 to 11.35, p=0.017). In Cox multiple regression analysis, sodium intake was
      inversely associated with all-cause (p=0.0069) and CVD mortality (p=0.086) and
      sodium/calorie ratio was directly associated with all-cause (p=0.0004) and CVD
      mortality (p=0.0056). By contrast, calorie intake in the presence of the two
      measures of sodium intake was not independently associated with mortality (all
      cause p=0.86; CVD p=0.74). Analysis restricted to participants with no history of
      CVD at baseline gave similar results. INTERPRETATION: This observational study
      does not justify any particular dietary recommendation. Specifically, these
      results do not support current recommendations for routine reduction of sodium
      consumption, nor do they justify advice to increase salt intake or to decrease
      its concentration in the diet.

PMID- 9519950
TI  - Randomised trial of isoniazid versus rifampicin and pyrazinamide for prevention
      of tuberculosis in HIV-1 infection.
AB  - BACKGROUND: Tuberculosis is a common complication of HIV-1 infection, especially
      in developing countries. Practical and effective chemoprophylaxis regimens for
      HIV-1-related tuberculosis are needed. Our aim was to test the efficacy of
      isoniazid versus rifampicin with pyrazinamide for prevention of tuberculosis in
      HIV-1-positive individuals. METHODS: We compared the efficacy of 6 months of
      isoniazid with 2 months of rifampicin and pyrazinamide for prevention of
      tuberculosis in HIV-1-seropositive individuals. Eligible participants were aged
      16-77 years, HIV-1 seropositive, had a positive purified-protein derivative (PPD)
      skin test reaction of at least 5 mm, and had a normal chest radiograph.
      Participants were randomly assigned partially supervised twice weekly isoniazid
      for 24 weeks or twice weekly rifampicin and pyrazinamide for 8 weeks.
      Participants were followed up for up to 4 years for the development of
      tuberculosis and survival. FINDINGS: Tuberculosis developed in 14 (3.8%) of 370
      participants assigned isoniazid and 19 (5.0%) of 380 participants assigned
      rifampicin and pyrazinamide (Cox model rate ratio 1.3 [95% CI 0.7-2.7]). The
      Kaplan-Meier estimate of the risk of tuberculosis during the first 10 months
      after entry was 3.7% among participants who received rifampicin and pyrazinamide
      compared with 1.0% (p=0.03) among participants who received isoniazid, and 5.4%
      versus 5.1%, respectively (p=0.9) at 36 months after entry. Higher rates of
      tuberculosis were observed in people with baseline CD4 percentages (of total
      lymphocytes) of less than 20 (rate ratio 4.0 [95% CI 1.8-9.0]). There were no
      significant differences in total mortality at any time. INTERPRETATION: Twice
      weekly isoniazid preventive therapy for 6 months or rifampicin and pyrazinamide
      for 2 months provided similar overall protection against tuberculosis in HIV-1
      infected, PPD-positive adults. The better protection among recipients of
      isoniazid during the first 10 months was most likely secondary to the longer
      duration of chemoprophylaxis. Preventive therapy for HIV-1-seropositive, PPD
      positive individuals could be practical in developing countries with a once
      weekly clinic visit, but optimum duration of chemoprophylaxis has not been
      determined.

PMID- 9519951
TI  - Immediate or delayed dissection of regional nodes in patients with melanoma of
      the trunk: a randomised trial. WHO Melanoma Programme.
AB  - BACKGROUND: The use of elective regional node dissection in patients with
      cutaneous melanoma without any clinical evidence of metastatic spread is still
      debated. Our aim was to evaluate the efficacy of immediate node dissection in
      patients with melanoma of the trunk and without clinical evidence of regional
      node and distant metastases. METHODS: An international multicentre randomised
      trial was carried out by the WHO Melanoma Programme from 1982 to 1989. The trial
      included only patients with a trunk melanoma 1.5 mm or more in thickness. After
      wide excision of primary melanoma, patients were randomised to either immediate
      regional node dissection or a regional node dissection delayed until appearance
      of regional-node metastases. FINDINGS: Of the 252 patients entered, 240 (95%)
      were eligible and evaluable for analysis. 122 of these were randomised to
      immediate node dissection. 5-year survival observed in patients who had delayed
      node dissection was 51.3% (95% CI 41.7-60.1) compared with 61.7% (52.0-70.1) of
      patients who had immediate node dissection (p=0.09). 5-year survival rate in
      patients with occult regional node metastases was 48.2% (28.0-65.8) and 26.6%
      (13.4-41.8, p=0.04) in patients in whom the regional node dissection was delayed
      until the time of appearance of regional node metastases. Multivariate analysis
      showed that routine use of immediate node dissection had no impact on survival
      (hazard ratio 0.72, 95% CI 0.5-1.02), whilst the status of regional nodes
      affected survival significantly (p=0.007). The patients with regional nodes that
      became clinically and histologically positive during follow-up had the poorest
      prognosis. INTERPRETATION: Node dissection offers increased survival in patients
      with node metastases only. Sentinel node biopsy may become a tool to identify
      patients with occult node metastases, who could then undergo node dissection.

PMID- 9519952
TI  - Quinolone resistance from a transferable plasmid.
AB  - BACKGROUND: Bacteria can mutate to acquire quinolone resistance by target
      alterations or diminished drug accumulation. Plasmid-mediated resistance to
      quinolones in clinical isolates has been claimed but not confirmed. We
      investigated whether a multiresistance plasmid could transfer resistance to
      quinolones between bacteria. METHODS: We transferred resistance between strains
      by conjugation. The resistance plasmid was visualised in different hosts by
      agarose-gel electrophoresis. We determined the frequency of spontaneous mutations
      to ciprofloxacin or nalidixic-acid resistance in Escherichia coli strains, with
      or without the quinolone resistance plasmid. FINDINGS: A multiresistance plasmid
      (pMG252) from a clinical isolate of Klebsiella pneumoniae was found to increase
      quinolone resistance to minimum inhibitory concentrations (MICs) as high as 32
      microg/mL for ciprofloxacin when transferred to strains of K pneumoniae deficient
      in outer-membrane porins. Much lower resistance was seen when pMG252 was
      introduced into K pneumoniae or E coli strains with normal porins. The plasmid
      had a wide host range and expressed quinolone resistance in other
      enterobacteriaceae and in Pseudomonas aeruginosa. From a plasmid-containing E
      coli strain with ciprofloxacin MIC of 0.25 microg/mL and nalidixic-acid MIC of 32
      microg/mL, quinolone-resistant mutants could be obtained at more than 100 times
      the frequency of a plasmid-free strain, reaching MICs for ciprofloxacin of 4
      microg/mL and for nalidixic acid of 256 microg/mL. INTERPRETATION: Transferable
      resistance to fluoroquinines and nalidixic acid has been found in a clinical
      isolate of K pneumoniae on a broad host range plasmid. Although resistance was
      low in wild-type strains, higher levels of quinolone resistance arose readily by
      mutation. Such a plasmid can speed the development and spread of resistance to
      these valuable antimicrobial agents.

PMID- 9519953
TI  - A period or not?

PMID- 9519954
TI  - Can magnetic-resonance imaging help elucidate natural history of breast cancer
      multicentricity?

PMID- 9519955
TI  - Galactorrhoea with moclobemide.

PMID- 9519956
TI  - Clinical experience of UK medical students.

PMID- 9519957
TI  - Eclampsia complicated by bilateral retinal detachments and abnormal eye
      movements.

PMID- 9519958
TI  - Junior doctors making mistakes.

PMID- 9519959
TI  - Extracorporeal photochemotherapy for chronic erosive lichen planus.

PMID- 9519960
TI  - Redefining vitamin D insufficiency.

PMID- 9519961
TI  - Oesophageal pressure during an earthquake.

PMID- 9519962
TI  - New data on passive smoking cause media uproar.

PMID- 9519964
TI  - Debate grows on safety of gene-therapy vectors.

PMID- 9519965
TI  - New imaging technology might help prevent stroke.

PMID- 9519968
TI  - Britain to debate how to plan for an ageing population.

PMID- 9519967
TI  - The warts and all approach to tackling cervical cancer.

PMID- 9519969
TI  - Woodward appeal rests on medical evidence.

PMID- 9519973
TI  - The viable myocardium: epidemiology, detection, and clinical implications.
AB  - The success of fibrinolytic and other therapies has reduced the mortality of
      myocardial infarction. However, many survivors develop congestive heart failure.
      Medical treatment of this disorder has limited efficacy, and cardiac
      transplantation has limited availability. Contrary to previous teaching about
      ischaemic injury, roughly 40% of segments involved in myocardial infarction may
      subsequently recover, either spontaneously or after revascularisation. The
      persistence of such viable myocardium means that previous approaches to treatment
      of myocardial infarction must be reappraised. This review examines the
      pathogenesis of this response, the techniques that may be used to identify the
      salvageable tissue, and the clinical implications. Myocardial revascularisation
      may improve symptom status, exercise capacity, and prognosis in selected patients
      with viable myocardium.

PMID- 9519974
TI  - Growth of civil society in developing countries: implications for health.
AB  - Owing to changes in political systems, the number of non-governmental
      organisations worldwide has increased substantially since 1980. The influence of
      civil society on health and health care depends on the recognition of its role as
      a partner in primary health care, on its success in the scaling up of activities,
      on its cooperation with the State and business sector, and on networking. In the
      event of health-sector reforms, civil society should focus on equity and justice,
      and advocate health as a public responsibility. The impact on health would
      increase if medical personnel joined forces with civil society and if medical
      schools added public speaking, networking, and lobbying to their agenda. The
      trend is that an increasing number of agents are getting involved in the
      promotion of health.

PMID- 9519975
TI  - Images of health.

PMID- 9519976
TI  - Why graduate medical schools make sense.

PMID- 9519977
TI  - Syndrome E.

PMID- 9519978
TI  - Syndrome E.

PMID- 9519979
TI  - Syndrome E.

PMID- 9519980
TI  - Syndrome E.

PMID- 9519981
TI  - Serbian doctors and ethnic Albanians.

PMID- 9519982
TI  - Absence of Bartonella-like inclusions in microangiopathy after transplantation.

PMID- 9519983
TI  - Topical tacrolimus for pyoderma gangrenosum.

PMID- 9519984
TI  - Incompatibility of insulin pens and cartridges.

PMID- 9519985
TI  - Incompatibility of insulin pens and cartridges.

PMID- 9519986
TI  - Folic acid food fortification to prevent neural tube defects.

PMID- 9519987
TI  - Folic acid food fortification to prevent neural tube defects.

PMID- 9519988
TI  - Plasma apolipoprotein A1 and birthweight.

PMID- 9519989
TI  - Albanian paradox, another example of protective effect of Mediterranean
      lifestyle?

PMID- 9519990
TI  - Albanian paradox, another example of protective effect of Mediterranean
      lifestyle?

PMID- 9519991
TI  - Angiotensin II, VEGF, and diabetic retinopathy.

PMID- 9519992
TI  - Angiotensin II, VEGF, and diabetic retinopathy.

PMID- 9519993
TI  - Endometrial changes during tamoxifen treatment.

PMID- 9519994
TI  - Needle-exchange programmes in the USA.

PMID- 9519995
TI  - Needle-exchange programmes in the USA.

PMID- 9519996
TI  - Global-warming and vector-borne disease in temperate regions and at high
      altitude.

PMID- 9519997
TI  - Categories of acute care.

PMID- 9520000
TI  - Myotonic dystrophy as a brain disorder.

PMID- 9520001
TI  - The genetics of Alzheimer disease: current status and future prospects.
AB  - Four genes involved in the development of Alzheimer disease have been identified.
      Three fully penetrant (deterministic) genes lead to the development of Alzheimer
      disease in patients younger than 60 years: the amyloid beta-protein precursor on
      chromosome 21, presenilin 1 on chromosome 14, and presenilin 2 on chromosome 1.
      Together, they account for about half of this early-onset form of the disease.
      One genetic risk factor--apolipoprotein E-4--is associated with late-onset
      Alzheimer disease. It accounts for a substantial fraction of disease burden but
      seems to act primarily to lower the age of disease onset. In general, none of
      these genes can be easily adapted for use as a diagnostic or predictive test for
      Alzheimer disease. Research activity includes searching for additional genes,
      especially for late-onset disease, and elucidating the mechanism of action of all
      identified genes as part of a long-term effort to develop more effective
      therapeutic and preventive strategies.

PMID- 9520002
TI  - Neurologic outcome of prematurity.
AB  - Brain injury in the premature infant is an extremely important problem, in part
      because of the large absolute number of infants affected yearly. The 2 principal
      brain lesions that underlie the neurological manifestations subsequently observed
      in premature infants are periventricular hemorrhagic infarction and
      periventricular leukomalacia. The emphases of this article are the
      neuropathological features, pathogenesis, and potential means of prevention of
      these 2 lesions. Recent work suggests that the ultimate goal, prevention of the
      lesions, is potentially achievable. Periventricular hemorrhagic infarction may be
      avoidable by prevention of germinal matrix-intraventricular hemorrhage, and
      periventricular leukomalacia by detection of impaired cerebrovascular
      autoregulation, prevention of impaired cerebral blood flow, and interruption of
      the cascade to oligodendroglial cell death by such agents as free radical
      scavengers.

PMID- 9520003
TI  - Pick's disease, frontotemporal dementia, and Pick complex: emerging concepts.

PMID- 9520004
TI  - Proton spectroscopy in myotonic dystrophy: correlations with CTG repeats.
AB  - OBJECTIVES: To seek cerebral metabolite abnormalities in patients with myotonic
      dystrophy and to determine whether the degree of cerebral abnormalities (measured
      by proton magnetic resonance spectroscopy) correlates with severity of the
      genetic defect (measured by trinucleotide repeats). DESIGN: Fourteen patients
      with myotonic dystrophy were compared with 24 healthy control subjects. SETTING:
      A university-affiliated medical center. RESULTS: Compared with healthy subjects,
      patients with myotonic dystrophy had elevated levels of myoinositol (+19% in the
      occipital region and +12.9% in the temporoparietal region), total creatine (+7.6%
      and +6.8%), and choline-containing compounds (+21% and +7.7%). Furthermore, the
      creatine and myoinositol peak areas correlated with the number of trinucleotide
      cytosine-thymine-guanine(n) (CTG)n repeats from leukocytes, especially in the
      temporoparietal brain region (r=0.76; P=.004). CONCLUSIONS: Neurochemical
      alterations observed with proton magnetic resonance spectroscopy are proportional
      to the cytosine-thymine-guanine repeat size. Increases in myoinositol and
      creatine concentrations may be caused by increased glial content, while elevated
      levels of choline-containing compounds are most likely caused by increased glial
      content and cell membrane abnormalities. Proton magnetic resonance spectroscopy
      is a powerful noninvasive tool to study brain biochemistry, which may reflect the
      extent of neuropathological involvement in patients with myotonic dystrophy.

PMID- 9520005
TI  - All-trans retinoic acid potentiates the ability of interferon beta-1b to augment
      suppressor cell function in multiple sclerosis.
AB  - OBJECTIVE: To determine the effects of combination all-trans retinoic acid (RA)
      and interferon beta-1b therapy on immune system functions potentially relevant to
      multiple sclerosis (MS). DESIGN: Interferon gamma-secreting cells, T suppressor
      cell function, and lymphocyte proliferative responses were assayed using
      peripheral blood mononuclear cells from patients with MS and control subjects
      under control conditions and in the presence of interferon beta-1b, RA, and the 2
      combined. SETTING: A university hospital MS clinic. PARTICIPANTS: Seventeen
      patients with secondarily progressive MS and 25 control subjects. RESULTS:
      Interferon beta-1b use increased interferon gamma-secreting cell counts,
      augmented T suppressor cell function, and inhibited T-cell proliferation. Therapy
      with RA decreased interferon gamma-secreting cell counts, had a minimal positive
      effect on T suppressor cell function, and had no effect on T-cell proliferation.
      When RA and interferon beta-1b were combined, the inhibitory effect of RA on
      interferon gamma-secreting cells predominated, T suppressor cell function
      increased synergistically over the increment observed with interferon beta-1b use
      alone, and the inhibitory effect of interferon beta-1b alone on T-cell
      proliferation remained unchanged. CONCLUSIONS: Treatment with interferon beta-1b
      partially restores defective T suppressor cell function in patients with MS. This
      potentially beneficial action is synergistically potentiated by RA. Interferon
      beta-1b increases the number of interferon gamma-secreting cells in the
      circulation when treatment is initiated. A similar increment in interferon gamma
      secreting cells is observed when interferon beta-1b is added to cultural
      peripheral blood mononuclear cells in vitro. This potentially deleterious action
      of interferon beta-1b is reversed by RA. Interferon beta-1b inhibits lymphocyte
      proliferation modestly but reproducibly. This action of interferon beta-1b is
      unaltered by RA. These data provide a rationale for a trial of combination
      treatment with interferon beta-1b and RA in patients with MS.

PMID- 9520006
TI  - Clinicopathologic studies in cognitively healthy aging and Alzheimer's disease:
      relation of histologic markers to dementia severity, age, sex, and apolipoprotein
      E genotype.
AB  - OBJECTIVE: To study differences between subjects with Alzheimer disease (AD) and
      cognitively intact control subjects, with respect to brain histologic markers of
      AD, and the relationship of those markers in the AD group to severity of
      dementia, age at death, sex, and apolipoprotein E genotype. SETTING: Washington
      University Alzheimer's Disease Research Center, St Louis, Mo. DESIGN AND
      SUBJECTS: Consecutive neuropathologic series of 224 prospectively studied
      volunteer research subjects, 186 with dementia of the Alzheimer type (DAT) or
      "incipient" DAT and confirmed to have AD by postmortem examination and 13
      cognitively intact subjects, confirmed to lack postmortem findings of AD. MAIN
      OUTCOME MEASURES: Brain densities (number per square millimeter) of senile
      plaques and neurofibrillary tangles, extent of cerebral amyloid angiopathy,
      cortical Lewy bodies, and apolipoprotein E genotype. RESULTS: Neocortical
      neurofibrillary tangle densities were substantially correlated with dementia
      severity, and to a greater degree than was true for senile plaque densities. When
      infarcts, hemorrhages, and Parkinson disease changes coexisted with AD,
      neurofibrillary tangle and senile plaque densities were lower. Plaque-predominant
      AD was found in a greater proportion of subjects with milder than more severe
      dementia. Entorhinal cortical Lewy bodies were no more frequent in plaque
      predominant AD than in the remaining AD cases. Increasing age at death was
      negatively correlated with dementia severity and densities of senile plaques and
      neurofibrillary tangles. The apolipoprotein E epsilon4 allele frequency was
      greater in AD than in control subjects but decreased with increasing age. After
      controlling for dementia severity, senile plaque densities were only weakly
      related to epsilon4 allele frequency, and only in hippocampus. However, the
      degree of cerebral amyloid angiopathy was clearly related to epsilon4 allele
      frequency. Among subjects diagnosed during life as having DAT or incipient DAT,
      only 7% were found to have a neuropathologic disorder other than AD causing their
      dementia. CONCLUSIONS: (1) The order of the strength of relationships between
      densities of histologic markers and dementia severity in AD is neurofibrillary
      tangles greater than cored senile plaques greater than total senile plaques. (2)
      Advanced age at death is associated with somewhat less severe dementia and fewer
      senile plaques and neurofibrillary tangles. (3) Plaque-predominant AD may
      represent a developmental stage in AD. (4) Despite a substantial effect of
      apolipoprotein E epsilon4 as a risk factor for AD, on decreasing the age at AD
      onset, and increasing the amount of cerebral amyloid angiopathy, its effect on
      senile plaque densities is variable and complex, being confounded with age,
      dementia severity, and methodologic differences. (5) Stringent clinical
      diagnostic criteria for DAT, even in the very mild stage, and senile plaque-based
      neuropathologic criteria for AD are highly accurate.

PMID- 9520007
TI  - Are generalized and localization-related epilepsies genetically distinct?
AB  - BACKGROUND: Whether the genetic influences are distinct for generalized and
      localization-related epilepsies or whether some susceptibility genes raise the
      risk for both types of epilepsy is uncertain. OBJECTIVE: To evaluate genetic
      heterogeneity in epilepsy. METHODS: We used Cox proportional hazards analysis to
      compute rate ratios (RRs) for generalized and localization-related idiopathic or
      cryptogenic epilepsy in the first-degree relatives of 1498 adult probands with
      idiopathic or cryptogenic epilepsy ascertained from voluntary organizations. The
      reference group comprised the first-degree relatives of 362 probands from the
      same study with postnatal symptomatic epilepsy in whom the genetic contributions
      appear to be minimal. RESULTS: In the parents and siblings, the risk for all
      idiopathic or cryptogenic epilepsy was greater if the proband's epilepsy was
      generalized than if it was localization-related (RR, 4.7 vs 2.4). However, in the
      parents and siblings of each group of probands, the increased risk was not
      restricted to the same type of epilepsy as in the proband. The results differed
      in offspring, with a greater risk for all types of epilepsy if the proband's
      epilepsy was localization-related than if it was generalized (RR, 4.2 vs 1.6) and
      a greater risk for localization-related epilepsy than for generalized epilepsy
      (RR, 7.8 vs 1.8) if the proband's epilepsy was localization-related. CONCLUSIONS:
      These findings in parents and siblings suggest that some susceptibility genotypes
      raise the risk for both generalized and localization-related epilepsies but are
      more common in persons affected with generalized epilepsy. The different findings
      in offspring may reflect a different influence on susceptibility in that
      subgroup.

PMID- 9520008
TI  - Failure of standard magnetic resonance imaging in patients with refractory
      temporal lobe epilepsy.
AB  - OBJECTIVE: To compare the sensitivity of standard magnetic resonance imaging
      (MRI) scans done outside an epilepsy center with that of special protocol MRI
      scans done at an epilepsy center in delineating relevant lesions of the temporal
      lobe. SUBJECTS: Eighty-four consecutive patients who had temporal lobe resections
      for refractory temporal lobe epilepsy between January 1, 1993, and February 1,
      1996. DESIGN: The reports of findings on standard MRI scans done outside an
      epilepsy center were compared with the findings of special protocol MRI scans
      done with 1.5-mm T1-weighted coronal and 3-mm T2-weighted coronal images (no
      gaps) on a 1.5-T system. Both sets of MRI findings were compared with findings on
      histologic examination of the resected tissue. RESULTS: Of the 84 patients, 51
      had standard MRI scans done outside an epilepsy center; of these, there were 34
      patients with normal results, 10 with tumors, 2 with vascular malformations, 2
      with hippocampal atrophy, 2 with unclassified abnormalities, and 1 with cortical
      malformation. In 32 of the 34 patients with normal results of an MRI scan done
      outside an epilepsy center, abnormalities were found on our special protocol MRI
      scans. These included hippocampal atrophy in 27 patients, tumors in 2, and
      cortical malformations in 1. Additionally, all 17 of the abnormalities detected
      on the standard MRI scans done outside the epilepsy center were identified on our
      special protocol MRI scans. Important pathologic abnormalities of the temporal
      lobe were identified in 16 (35%) of the 46 patients with standard MRI scans done
      outside an epilepsy center and in 44 (96%) with our special protocol MRI scans.
      In the 29 patients for whom adequate surgical specimens were available and
      results of standard MRI scans were normal, our special protocol MRI scans showed
      the abnormality in 27 (93%). CONCLUSIONS: Conventional neuroimaging studies are
      inadequate for diagnosing hippocampal sclerosis although they fairly readily
      detect low-grade tumors and vascular malformations. Magnetic resonance imaging
      scans for the evaluation of patients with refractory temporal lobe epilepsy
      should be done with a special temporal lobe protocol and read by physicians
      experienced with the findings in hippocampal sclerosis. Health care dollars are
      wasted on neuroimaging done for refractory temporal lobe epilepsy outside
      epilepsy centers.

PMID- 9520009
TI  - A 7 minute neurocognitive screening battery highly sensitive to Alzheimer's
      disease.
AB  - OBJECTIVE: To determine the validity and reliability of a rapidly administered
      neurocognitive screening battery consisting of 4 brief tests (Enhanced Cued
      Recall, Temporal Orientation, Verbal Fluency, and Clock Drawing) to distinguish
      between patients with probable Alzheimer's disease (AD) and healthy control
      subjects. SUBJECTS: Sixty successive referrals to the Memory Disorders Clinic at
      Southwestern Vermont Medical Center, Bennington, who were diagnosed as having
      probable AD and 60 community-dwelling volunteers of comparable age, sex
      distribution, and education. DESIGN: Interrater and test-retest reliability,
      intergroup comparisons between patients with AD and control subjects on the 4
      individual tests, and determination of probability of dementia for patients with
      AD and control subjects using the entire battery of tests. SETTING: Outpatient
      care. MAIN OUTCOME MEASURE: Comparison of the probability of dementia on the 7
      Minute Screen with the criterion standard of clinical diagnosis established by
      examination and laboratory studies. SECONDARY OUTCOME MEASURES: Test-retest and
      interrater reliability (correlation coefficients), time for administration.
      RESULTS: Mean time of administration was 7 minutes 42 seconds. Mean scores for
      patients with AD and control subjects on all 4 individual tests were
      significantly different (for each, P<.001). When the 4 tests were combined in a
      logistic regression, the battery had a sensitivity of 100% and a specificity of
      100%. A series of 1000 repeated random samples of 30 patients with AD and 30
      control subjects taken from the overall sample of 60 patients with AD and 60
      control subjects had a mean sensitivity of 92% and a mean specificity of 96%. The
      battery was equally sensitive to patients with mild AD as demonstrated by
      correctly classifying all 13 patients with AD using Mini-Mental State Examination
      scores of 24 or higher. Neither age nor education was a statistically significant
      factor when added as a covariate. Test-retest reliabilities for individual tests
      ranged from 0.83 to 0.93. Test-retest reliability for the entire battery was
      0.91. Interrater reliability for the entire battery was 0.92. CONCLUSIONS: The 7
      Minute Screen appears highly sensitive to AD and may be useful in helping to make
      initial distinctions between patients experiencing cognitive changes related to
      the normal aging process and those experiencing cognitive deficits related to
      dementing disorders such as AD. It has reasonable interrater and test-retest
      reliability, can be administered in a brief period, and requires no clinical
      judgment and minimal training.

PMID- 9520010
TI  - Diagnostic validity of the dementia questionnaire for Alzheimer disease.
AB  - OBJECTIVE: To determine the sensitivity and specificity of postmortem dementia
      diagnoses based on a retrospective informant interview by comparison with
      criterion standard neuropathological diagnoses and the results of previous
      clinical examinations. SETTING: Three university-based academic research centers.
      SUBJECTS: Fifty-four deceased elderly persons with Alzheimer disease, another
      dementing disorder, a neurologic disease resulting in functional impairment but
      no dementia, or no neurologic disorder. METHODS: Blinded nonclinician
      interviewers administered the Dementia Questionnaire (DQ) by telephone to
      informants, typically close relatives, who were familiar with the intellectual
      and functional status of the subjects before death. Two senior clinicians (LJ.T.
      and C.K.) rated each DQ for the presence or absence of a dementia syndrome during
      life and for the specific disorders causing the dementia, if present. Raters were
      blinded to the neuropathological findings and based their assessments only on
      data provided by responses to the DQ. Comparison was made with diagnoses based on
      neuropathological assessment. In most cases, the results of antemortem clinical
      examinations were also available as a check on the clinical diagnosis of the
      dementia syndrome. Sensitivity and specificity of the DQ diagnoses were computed,
      and chance-corrected agreement measures were calculated for the 2 independent DQ
      raters (LJ.T. and C.K.). RESULTS: Compared with antemortem clinical diagnosis,
      the average sensitivity of the DQ for the clinical syndrome of dementia was
      92.8%, the specificity was 89.5%, and the interrater agreement was 98% (kappa =
      0.96). Among 7 subjects with mild dementia (Mini-Mental State Examination score >
      or = 24 at the last clinical examination), 5 (71%) were correctly identified
      using the DQ. The DQ correctly indicated the absence of dementia in 8 (80%) of 10
      subjects with other neurologic disorders causing functional impairment. Compared
      with the neuropathological diagnoses, the DQ differentiated Alzheimer disease
      from other primary causes of dementia with a sensitivity of 89% and a specificity
      of 72%. The interrater agreement was 93.8% (kappa = 0.85). CONCLUSIONS: Compared
      with the results of the antemortem clinical examinations, the DQ was sensitive to
      the presence of dementia, detected most cases of mild dementia, and discriminated
      dementia from other neurologic disorders causing functional impairment. Compared
      with the neuropathological diagnoses, the ability of the DQ to differentiate
      Alzheimer disease from other dementing disorders indicates that it may be useful
      as a research tool.

PMID- 9520011
TI  - Cognitive dysfunction and impaired organization of complex motility in
      degenerative parkinsonian syndromes.
AB  - BACKGROUND: A frontostriatal pattern of cognitive decline, consisting of a
      frontal lobe-like syndrome without genuine cortical defects such as amnesia,
      apraxia, aphasia, or agnosia, is well established in basal ganglial diseases.
      Recent pathological investigations, however, have again noted cortical damage in
      progressive supranuclear palsy (PSP), suggesting that cortical defects could be
      present. OBJECTIVES: To delineate the pattern of cognitive impairment and to
      detect higher-order motor impairments (including ideomotor apraxia) in
      parkinsonian syndromes. PATIENTS AND METHODS: We assessed ideomotor apraxia, and
      simple and sequential tapping in patients with Parkinson disease, multiple system
      atrophy, and PSP with similar disease severity, age range, and education. We also
      administered a comprehensive battery of neuropsychological tests to examine
      general intelligence, memory, executive functions, attention, and visuospatial
      orientation. The results were compared between groups and with a matched normal
      control group. RESULTS: Sequential tapping and the imitation of sequences of
      gestures were impaired in all patient groups, with patients with PSP performing
      worse than the other groups. Based on ideomotor apraxia scores and a qualitative
      analysis of errors, 3 patients with PSP and 2 with multiple system atrophy were
      considered apraxic. General intelligence and executive functions were compromised
      in all patient groups. The impairment of patients with PSP was more pervasive
      than that of the other groups, and included compromise of visuospatial functions,
      attention, and memory. Discriminant analysis of all cognitive and motor tests
      showed that the tapping and ideomotor apraxia tests best identified the patients
      vs control subjects. CONCLUSIONS: The presence of cortical as well as subcortical
      damage in patients with PSP and those with multiple system atrophy is indicated
      by the presence of pervasive cognitive and motor disturbances in the former,
      substantial motor disorganization in the latter, and the finding of ideomotor
      apraxia in some patients with these diseases. Furthermore, the discovery that
      tests of motor and gesture best identified all patients vs control subjects is
      consistent with the existence of a common motor disorganization in these
      parkinsonian syndromes, in agreement with the known damage to the corticostriatal
      pathways in these conditions.

PMID- 9520012
TI  - Poor mental development in patients with tuberous sclerosis complex: clinical
      risk factors.
AB  - OBJECTIVE: To identify clinical risk factors for poor mental development among
      patients with tuberous sclerosis complex (TSC). DESIGN: Case-control analysis of
      a clinic population. SETTING: Specialty clinic in a hospital. PATIENTS: One
      hundred six patients with TSC consecutively seen between January 1984 and
      December 1995 at the Child Neurology Clinic of the Children's Memorial Health
      Institute in Warsaw, Poland. STUDY VARIABLES: Seizure type, age at seizure onset,
      sex, and history of diphtheria, tetanus, and pertussis immunization. MAIN OUTCOME
      MEASURE: Moderate to profound developmental delays. RESULTS: Seizure type (ie,
      infantile spasms) was the only analyzed risk factor that showed a consistent and
      independent association with poor mental development (adjusted odds ratio, 3.0;
      95% confidence interval, 1.1-8.4; P =.03). Age at seizure onset, which initially
      showed a significant association with poor mental development, was no longer
      significantly associated after adjustment for seizure type (adjusted odds ratio,
      1.6; P = .43). Neither sex (odds ratio, 1.1; P = .96) nor history of diphtheria,
      tetanus, and pertussis immunization (odds ratio, 1.0; P = .80) showed evidence of
      being a risk factor for poor mental development among patients with TSC.
      CONCLUSIONS: Infantile spasms, as the type of seizure on initial examination, is
      a significant risk factor for poor mental development in patients with TSC. Age
      at time of first seizure is not an independent risk factor but reflects the early
      ages at which these patients are seen with infantile spasms. Neither sex nor
      history of diphtheria, tetanus, and pertussis immunization is a risk factor for
      the subsequent development of poor mental development among patients with TSC.

PMID- 9520013
TI  - The effect of patient attrition on estimates of the frequency of dementia
      following stroke.
AB  - BACKGROUND: Given that prevalence surveys may underestimate the magnitude of the
      association between an exposure and a disease with high morbidity or mortality,
      we investigated the effects of patient attrition on estimates of the frequency of
      dementia following ischemic stroke. PATIENTS AND METHODS: We examined 251
      patients 3 months after stroke and diagnosed dementia in 66 (26.3%) based on the
      results of neuropsychological and functional assessments and modified criteria
      from the Diagnostic and Statistical Manual of Mental Disorders, Third Edition,
      Revised. Those 251 patients were drawn from a larger cohort of 297 patients, with
      the majority of the remaining 46 patients being unavailable for assessment due to
      death, severe stroke, or comorbid medical disorders. Using the coefficients in a
      logistic model of the clinical determinants of dementia based on the 251 patients
      who were examined, we calculated the probability of dementia for each of the 46
      patients who were not examined. We considered a patient to have dementia when
      that probability was higher than the mean of the median probabilities of dementia
      in the groups of patients with and without dementia who completed the
      examinations. RESULTS: The sensitivity and specificity of our diagnostic method
      were 75.8% and 72.4%, respectively. We recognized dementia in 21 (45.7%) of the
      46 unavailable patients, a significantly higher frequency than among examined
      patients. Additional analyses determined that the factors that increased the risk
      of becoming unavailable for follow-up, which included more severe stroke, left
      and right hemisphere infarct locations, and a history of prior stroke, are
      similar to the factors that increase the risk of dementia after stroke.
      CONCLUSION: Our findings suggest that dementia is differentially associated with
      early patient attrition, potentially resulting in the underestimation of its
      frequency and underrecognition of its importance as an outcome of ischemic
      stroke.

PMID- 9520014
TI  - A prospective study of cognitive function and onset of dementia in cognitively
      healthy elders.
AB  - OBJECTIVE: To examine the earliest cognitive changes associated with the onset of
      dementia as well as changes associated with normal aging. DESIGN: Longitudinal
      evaluation of participants with annual clinical and psychometric examinations for
      up to 15 1/2 years. SETTING AND PARTICIPANTS: Elderly volunteers (n = 82)
      enrolled with a Clinical Dementia Rating of 0 (cognitively intact) in
      longitudinal studies. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Clinical
      Dementia Rating and results of a 1 1/2-hour psychometric battery. RESULTS: As
      estimated with survival analysis, 40% of participants had a Clinical Dementia
      Rating greater than 0 (cognitive decline) within 12 years of enrollment; 59% of
      these were judged to have dementia of the Alzheimer type or incipient dementia.
      Participants with poorer performance on psychometric testing at enrollment were
      at higher risk for cognitive decline subsequently. The rate of change in
      psychometric performance before clinically detectable cognitive change occurred
      was not significantly different between those who eventually developed dementia
      and those who remained stable, except for performance on the Logical Memory
      subtest of the Wechsler Memory Scale. When subtle cognitive decline was
      clinically detected, however, an abrupt deterioration in performance on
      independently administered psychometric tests was observed. CONCLUSIONS:
      Cognitively healthy elderly people maintain stable cognitive performance when
      measured longitudinally by both careful clinical evaluation and repeated
      psychometric testing. This stability is maintained unless and until they develop
      a dementing illness, at which time a sharp decline in performance is observed.

PMID- 9520015
TI  - Paraneoplastic cerebellar syndrome and optic neuritis with anti-CV2 antibodies:
      clinical response to excision of the primary tumor.
AB  - OBJECTIVE: To describe a patient with a paraneoplastic cerebellar syndrome and
      optic neuritis with circulating anti-CV2 antibodies and clinical improvement
      after excision of a small cell lung carcinoma. DESIGN: Report of a case. SETTING:
      A 62-year-old man simultaneously developed a severe cerebellar syndrome and a
      bilateral optic neuritis predominantly in the left eye (visual acuity, 20/25 in
      the right eye; < 20/400 in the left eye; and bilateral swelling of the optic
      discs). MAIN OUTCOME AND RESULTS: Anti-CV2 antibodies, recently described as
      associated with paraneoplastic neurological syndrome, were detected in the
      patient's serum sample. These antibodies were demonstrated to react with the
      cytoplasm of a subpopulation of oligodendrocytes in the white matter of rat brain
      in the cerebellum, brainstem, spinal cord, and optic chiasm. The patient was
      found to have a small cell lung carcinoma, which was removed. After excision of
      the tumor, the cerebellar syndrome improved dramatically and the papilledema
      disappeared despite aftereffects of the optic neuritis. CONCLUSIONS: These
      findings were consistent with the diagnosis of a paraneoplastic neurological
      syndrome, although both optic neuritis and remission of the cerebellar syndrome
      are uncommon patterns of paraneoplastic syndromes. CV2 antigen expression by the
      oligodendrocytes of the cerebellum, brainstem, spinal cord, and optic chiasm
      correlated with the clinical syndrome observed in our patient. However, the
      precise pathophysiological role of anti-CV2 antibodies is still unknown.

PMID- 9520016
TI  - Unrecognized Tourette syndrome in adult patients referred for psychogenic tremor.
AB  - BACKGROUND: The diagnosis of Tourette syndrome may be overlooked in patients with
      severe psychopathologic disorder but mild motor manifestations of Tourette
      syndrome. OBJECTIVE: To describe 4 patients with long-lasting general
      psychopathologic disorder and previously unrecognized mild motor and phonic tics
      exacerbated during adulthood by the onset of tremor; all of the patients had been
      referred for the evaluation of psychogenic tremor. SUBJECTS: Four adult patients,
      with previous psychiatric diagnoses of depression (2 cases), generalized anxiety
      disorder (3 cases), malingering (1 case), and conversion disorder (3 cases).
      METHODS: Single case studies. RESULTS: Clinical interviews disclosed that the 4
      patients had positive family histories of Tourette syndrome, and all had mild
      motor and phonic tics that had started before the age of 18 years. On neurologic
      examination, 2 patients had bilateral postural tremor of the hands that varied in
      frequency, rhythmicity, and amplitude, and the other 2 had resting tremor
      mimicking parkinsonism. All 4 patients described involuntary somatic sensations
      of the affected limbs, which they attempted to alleviate by executing movements.
      No consistent positive placebo response was observed, but in all patients
      tremoric movements improved with haloperidol. CONCLUSIONS: These cases illustrate
      an unusual movement disorder (tremor as a "tic equivalent") in adults with
      Tourette syndrome and emphasize that cases of the syndrome with mild tics often
      go unrecognized, precluding adequate treatment.

PMID- 9520017
TI  - Corticosteroid-responsive postmalaria encephalopathy characterized by motor
      aphasia, myoclonus, and postural tremor.
AB  - OBJECTIVES: To study the clinical spectrum of an acute severe encephalopathy
      occurring in 2 patients after recovery from falciparum malaria infection and to
      compare it with the reported clinical features of the postmalaria neurological
      syndrome. DESIGN: Case report. SETTING: Tertiary care hospital. PATIENTS: Two
      patients presented with acute onset of fluctuating motor aphasia, severe
      generalized myoclonus, and postural tremor. Additional signs were cerebellar
      ataxia, and in 1 patient, generalized epileptic seizures. Magnetic resonance
      imaging of the brain revealed patchy white matter lesions in 1 patient.
      Clinically, the patients' conditions continued to worsen until corticosteroids
      were introduced, the use of which induced a rapid, albeit incomplete, recovery.
      CONCLUSIONS: We describe a new, severe variant of the still poorly defined
      postmalaria neurological syndrome. We propose a preliminary classification of
      this syndrome, according to its clinical characteristics, as follows: a mild or
      localized form, characterized by isolated cerebellar ataxia or postural tremor; a
      diffuse, but relatively mild encephalopathic form, characterized by acute
      confusion or epileptic seizures; and a severe, corticosteroid-responsive
      encephalopathy that is characterized by motor aphasia, generalized myoclonus,
      postural tremor, and cerebellar ataxia.

PMID- 9520018
TI  - Multiple sclerosis.

PMID- 9520019
TI  - Graft-versus-host reactions in dermatology.
AB  - Graft-versus-host reactions frequently produce cutaneous and systemic
      complications in patients receiving bone marrow transplants. Characteristic skin
      involvement typically heralds graft-versus-host reactions and significantly
      contributes to the morbidity associated with marrow transplants. Familiarity with
      these reactions and their treatment is important to dermatologists involved in
      the care of marrow transplant recipients.

PMID- 9520020
TI  - Dermatomyositis: a dermatology-based case series.
AB  - BACKGROUND: Dermatomyositis is associated with significant morbidity and
      occasional mortality. Currently there is no consensus on treatment for patients
      with dermatomyositis. OBJECTIVE: Our purpose was to review the clinical features
      and response to therapy of patients with dermatomyositis and compare these data
      with previous series of patients with dermatomyositis/polymyositis. METHODS:
      Clinical characteristics of 65 patients seen during a 10-year period were
      reviewed retrospectively. Twenty-one of these patients were enrolled in a
      prospective, uncontrolled study of treatment with high-dose prednisone followed
      by slow tapering. RESULTS: Clinical features were similar to those previously
      described; however, muscle strength at diagnosis was on average greater in
      patients in this series than in patients previously reported. Malignancy was
      present in 5 of 43 adult patients (12%), but was not found in patients with
      juvenile dermatomyositis. Another connective tissue disease was present in 19% of
      patients. Twelve patients had dermatomyositis sine myositis. Eighteen of 21
      patients (85%) in the prednisone study group had resolution of myositis.
      CONCLUSION: Patients with dermatomyositis in this series had less active myositis
      at presentation, but were otherwise similar to patients with
      dermatomyositis/polymyositis previously reported. Treatment with high-dose daily
      prednisone followed by slow tapering was effective.

PMID- 9520021
TI  - Subacute cutaneous lupus erythematosus versus systemic lupus erythematosus:
      diagnostic criteria and therapeutic implications.
AB  - BACKGROUND: The nosologic position of subacute cutaneous lupus erythematosus
      (SCLE) is controversial. More than four American Rheumatism Association (ARA)
      criteria for systemic lupus erythematosus (SLE) are found in a proportion of
      patients diagnosed as having SCLE; thus such cases could be classified as SLE.
      OBJECTIVE: Our purpose was to determine whether ARA criteria for SLE are helpful
      in differentiating SCLE from SLE and whether cutaneous and visceral changes,
      immunologic findings, and photosensitivity provide a basis for diagnosis of SCLE.
      METHODS: A cohort of 143 patients (79 with SCLE, 58 with SLE, and six with
      overlapping features of SCLE and SLE) was studied clinically, histologically, and
      immunologically as well as by phototesting. The patients were observed for up to
      10 years, and the course of the disease and response to therapy were evaluated in
      each group. RESULTS: SCLE differed from SLE by cutaneous changes, significantly
      less frequent kidney involvement, serositis and arthritis, and the rare presence
      of double-stranded DNA, U1RNP, and Sm antibodies characteristic of SLE. Ro(SS-A)
      and La(SS-B) antibodies were detected with similar frequency, and
      photosensitivity was not related to the presence of Ro antibody. In contrast,
      photoreproduction (appearance of LE lesion in irradiated area) was significantly
      more frequent in patients with SCLE. The course of SCLE in older patients was
      less severe than in younger patients, and aggressive therapy was usually not
      required. CONCLUSION: Patients with SCLE (although the majority fulfill more than
      four ARA criteria for SLE) show significant differences from those with SLE in
      terms of cutaneous and visceral involvement, immunologic findings,
      photosensitivity, course of the disease, and the requirement for therapy.
      Therefore SCLE should be recognized as a separate subset. However, cases of
      overlapping SLE and SCLE suggest a close relation.

PMID- 9520022
TI  - Skin cancer prevention for children, parents, and caregivers: a field test of
      Hawaii's SunSmart program.
AB  - BACKGROUND: Children are at particular risk for sun exposure, a major cause of
      skin cancer. Parents and caregivers can help protect children by educating them
      about practicing safe sun habits, serving as role models, and providing
      supportive environments. OBJECTIVE: We evaluated SunSmart, a cancer prevention
      program for 6- to 8-year-old children, their parents, and outdoor recreation
      staff. METHODS: The intervention included staff training, on-site activities for
      children, interactive take-home booklets, behavior-monitoring scoreboards,
      incentives, providing sunscreen, and encouraging sun safe environments and
      policies. The program was evaluated by baseline and follow-up surveys of parents
      and recreation staff, monitoring forms, and on-site observations. RESULTS: There
      were positive changes in all major outcomes, including knowledge; sun protection
      habits of parents, children, and staff; readiness to change; sun protection
      policies; and sun protection norms. The changes ranged from improvements of 3% to
      more than 20%, and several changes were statistically significant. CONCLUSION:
      The results demonstrated the feasibility and short-term impact of Hawaii's
      SunSmart program and suggested areas for refinement and expansion.

PMID- 9520023
TI  - Alopecia areata and cytomegalovirus infection in twins: genes versus environment?
AB  - BACKGROUND: Alopecia areata (AA) is hypothesized to be an organ-specific
      autoimmune disease mediated by T cells directed to the hair follicle. Genetic
      susceptibility may be conferred by HLA, and an environmental trigger, such as a
      viral infection, is suspected. The incidence of AA in the population is estimated
      to be 1.7%, with an average of one in four patients having a positive family
      history. OBJECTIVE: Our purpose was to examine the concordance rate of AA among
      identical versus fraternal twins and the correlation between stress,
      cytomegalovirus (CMV) infection, and disease. METHODS: Families with AA were
      solicited from dermatologists in the United States and through a Website on the
      Internet. HLA class 2 typing and identification of CMV early and late genes were
      performed by polymerase chain reaction (PCR) on genomic peripheral blood DNA.
      Serum antibodies for CMV were determined by enzyme-linked immunosorbent assay.
      RESULTS: From 114 families, we identified 11 sets of monozygotic twins and 3 sets
      of dizygotic twins. The concordance rate was 55% for monozygotic twins and 0% for
      fraternal twins. Most identical twins were male. The severity of the AA phenotype
      varied and appeared most severe in the first affected twin. Five of 24 twins were
      CMV seropositive but CMV DNA was not detected in blood lymphocytes of any of the
      subjects when studied after the onset of AA. The presence of AA in twins was not
      correlated with evidence of CMV. CONCLUSION: A 55% concordance rate in identical
      twins and AA occurring in families support a genetic component as well as
      possible environmental triggers that remain unknown.

PMID- 9520024
TI  - Absence of human papillomavirus DNA in the plume of erbium:YAG laser-treated
      warts.
AB  - BACKGROUND: The erbium:YAG laser (Continuum Biomedical, Dublin, Calif.) is a new
      resurfacing and ablating laser that produces minimal residual thermal damage.
      Laser safety requires careful attention to the hazards of the laser plume. It is
      important to know whether viable organisms survive in the vapors. Human
      papillomavirus (HPV) DNA has been detected in the vapor of carbon dioxide laser
      treated and electrodesiccated human warts. The presence or absence of HPV DNA in
      the laser plume of erbium:YAG laser-treated warts has not been previously studied
      to our knowledge. OBJECTIVE: Our purpose was to determine the presence or absence
      of HPV DNA in the laser plume of erbium:YAG laser-treated human warts. METHODS:
      One half of clinically typical and histopathologically confirmed verrucae
      vulgares from five patients were submitted for HPV DNA detection with in situ
      hybridization. After erbium:YAG laser ablation of the remainder of the warts, the
      laser plume was deposited on the handpiece as an abundant fluffy material and was
      submitted for evaluation of HPV DNA by polymerase chain reaction with consensus
      primers for the HPV type detected in the wart specimens. RESULTS: HPV2 DNA was
      found in all warts. HPV DNA was not detected in the erbium:YAG laser plume after
      ablation of these same warts. CONCLUSION: The absence of HPV DNA in the plume of
      erbium:YAG laser-treated warts is a significant safety feature of this laser.

PMID- 9520025
TI  - Detection of human herpesvirus-8 DNA in Kaposi's sarcomas from iatrogenically
      immunosuppressed patients.
AB  - BACKGROUND: Kaposi's sarcoma (KS) accounts for more than 5% of malignancies in
      immunosuppressed organ transplant patients (OKS). A new herpesvirus (HHV-8) was
      identified with high prevalence in biopsy specimens of AIDS-KS, endemic KS, and
      classic KS and in OKS. KS has also been associated with other underlying diseases
      in patients treated with corticosteroids, but this subset of KS has been reported
      to contain HHV-8 in only a few case reports. OBJECTIVE: In this larger study, we
      determined the prevalence of HHV-8 in seven patients of Jewish origin in whom KS
      developed during immunosuppressive therapy for different primary diseases (ISKS).
      METHODS: The study included HHV-8 DNA detection by polymerase chain reaction
      (PCR) coupled with Southern blot and sequence analysis as well as by in situ
      hybridization. RESULTS: HHV-8 sequences were detected by PCR with confirmation by
      Southern blot and sequence analysis in 100% of the ISKS samples. Direct
      sequencing revealed several previously unknown base changes within the 208 bp
      region from open reading frame 26 (ORF26[208]) of HHV-8 in ISKS. CONCLUSION: Ours
      is the largest known study describing the presence of HHV-8 in iatrogenic KS from
      immunosuppressed nontransplant patients and provides data of previously unknown
      sequence variations within the ORF26 of HHV-8 DNA.

PMID- 9520027
TI  - Efficacy of itraconazole in children with Trichophyton tonsurans tinea capitis.
AB  - BACKGROUND: Tinea capitis is prevalent in children. Although widely used as the
      drug of choice, the response to griseofulvin may be incomplete and an extended
      duration of therapy is often required. The response to newer antifungals has not
      been methodically evaluated in children with Trichophyton tonsurans infection.
      OBJECTIVE: Our purpose was to determine the efficacy of itraconazole in children
      with tinea capitis caused by T. tonsurans. METHODS: Pediatric patients with
      culture proven tinea capitis were enrolled from a hospital-based primary care
      clinic between January and December of 1996. Patients were treated with
      itraconazole 100 mg/day and a selenium sulfide-containing shampoo for 4 weeks.
      Children were evaluated mycologically and clinically every 2 weeks for 2 months.
      Patients were considered successfully treated if they were culture negative and
      clinically improved at the end of the study period. Children who remained culture
      positive or who were clinically not improved at 2 months were classified as
      treatment failures and retreated. RESULTS: Twenty-five patients completed the
      study, and 10 (40%) were successfully treated. Fifteen children required re
      treatment: 14 remained culture positive at week 8, and one was mycologically
      negative but clinically worse. CONCLUSION: Itraconazole at a dose of 100 mg/day
      for 4 weeks may be effective in less than half of children with T. tonsurans
      tinea capitis.

PMID- 9520028
TI  - Safety of solar phototherapy at the Dead Sea.
AB  - BACKGROUND: Climatotherapy at the Dead Sea is effective for patients with
      psoriasis, atopic dermatitis, vitiligo, and other diseases. Although impressive
      improvement has been reported for patients with psoriasis, with a clearance rate
      of more than 80% after a 4-week stay, questions regarding the safety of this
      treatment have arisen. OBJECTIVE AND METHODS: We compare the mean UVB radiation
      intensities absorbed by psoriatic patients undergoing a 4-week climatotherapy
      under supervision at the DMZ Rehabilitation Clinic of Ein-Bokek (The Dead Sea,
      Israel), with similar climatotherapy studies in Sweden and Switzerland. We also
      compare the climatotherapy radiation dosages with the UVB intensities absorbed by
      psoriatic patients in radiation cabins at seven university clinics. RESULTS:
      According to our individually computerized DMZ protocol, a psoriasis patient with
      skin type IV is exposed during a 4-week climatotherapy to a mean 3.11 J/cm2 (148
      MED) of UVB, similar to that in Sweden and Switzerland. The range of the in
      clinic annual phototherapy in the seven medical centers studied varied from 1.17
      to 37.80 J/cm2 (56 to 1800 MED). CONCLUSION: When all relevant factors are taken
      into account, the mean UVB exposure dose at the Dead Sea is one of the lowest
      reported for clearance of psoriatic plaques.

PMID- 9520026
TI  - Intratumoral chemotherapy with fluorouracil/epinephrine injectable gel: a
      nonsurgical treatment of cutaneous squamous cell carcinoma.
AB  - BACKGROUND: We attempted to originate a nonsurgical treatment alternative for
      cutaneous squamous cell carcinoma (SCC), and we evaluated intratumoral modified
      release chemotherapy with fluorouracil/epinephrine injectable gel (5-FU/epi gel).
      OBJECTIVE: To assess the safety and efficacy, we conducted an open-label pilot
      study of 5-FU/epi gel in 25 patients with biopsy-proven SCC lesions on the face,
      head, neck, trunk, arms, and hands. METHODS: Each tumor site was injected
      intradermally with up to 1.0 ml of 5-FU/epi gel. One SCC per patient was treated
      weekly for up to 6 weeks, then observed for 4 months at which time the tumor site
      and margins were excised for histologic examination. RESULTS: Overall, 96% (22 of
      23) of evaluable treated tumors had histologically confirmed complete tumor
      clearing. No clinically significant systemic reactions or unexplained treatment
      related adverse medical events occurred. The evaluations of the cosmetic
      appearance of the treated sites, judged subjectively by clinicians and patients,
      were mostly good to excellent and generally in close agreement. CONCLUSION:
      Treatment of superficial SCC with 5-FU/epi injectable gel results in a high rate
      of histologically confirmed complete tumor responses and may provide a
      nonsurgical treatment alternative in selected patients.

PMID- 9520029
TI  - Detection of clonal T-cell receptor gamma chain gene rearrangements by polymerase
      chain reaction and denaturing gradient gel electrophoresis (PCR/DGGE) in archival
      specimens from patients with early cutaneous T-cell lymphoma: correlation of
      histologic findings with PCR/DGGE.
AB  - BACKGROUND: Early stages of cutaneous T-cell lymphoma (CTCL) may be difficult to
      distinguish from benign inflammatory dermatoses by routine histologic
      examination. OBJECTIVE: Our purpose was to determine whether clonal
      rearrangements of the T-cell receptor (TCR) gamma gene by polymerase chain
      reaction and denaturing gradient gel electrophoresis (PCR/DGGE) could be detected
      in the early stages of CTCL and to correlate these findings with conventional
      histopathology. METHODS: A total of 39 specimens from 12 patients with CTCL were
      obtained. The slides were evaluated independently by three dermatopathologists,
      and categorized into three groups: nondiagnostic, suggestive of CTCL, and
      diagnostic of CTCL. Of the 39 specimens, 33 were tested by PCR/DGGE by means of
      GC-clamped primers for clonal rearrangement of the TCR gamma gene. RESULTS: The
      histologic evaluation of the 12 cases showed a significant variation among the
      three dermatopathologists. The correlation of PCR/DGGE with routine histology was
      as follows: Clonal TCR gamma gene rearrangements were demonstrated in 73% of the
      specimens nondiagnostic for CTCL, 71% of those suggestive of CTCL, and 74% of
      those diagnostic of CTCL. CONCLUSION: Clonal TCR gamma gene rearrangements may be
      detected in patients with early CTCL, even when the histologic findings are not
      unequivocally diagnostic. In patients with multiple biopsy specimens, identical
      clones were demonstrated in all rearranged samples, indicating the same
      neoplastic clone was present in the earliest stages of disease.

PMID- 9520030
TI  - Sclerotherapy for the permanent eradication of varicose veins: theoretical and
      practical considerations.
AB  - Although sclerotherapy is an established procedure to treat ectatic veins, a wide
      disparity remains in the reported rates of success, especially for larger
      varicose veins. This article reviews the venous anatomy of the lower extremity
      and outlines the indications for sclerotherapy. The historical basis for
      treatment techniques is explored. The mechanism of action of sclerotherapy is
      discussed as a basis for treatment guidelines. If the procedure is properly
      performed, when appropriately indicated, rates of success should approach 100%.

PMID- 9520031
TI  - Surgical Pearl: Lateral rhinotomy for exposure of tumors of the nasal vestibule.

PMID- 9520032
TI  - Methotrexate in psoriasis: consensus conference.

PMID- 9520033
TI  - New-onset Majocchi's granuloma in two kidney transplant recipients under
      tacrolimus treatment.

PMID- 9520034
TI  - Invasive cutaneous aspergillosis complicating immunosuppressive therapy for
      recalcitrant pemphigus vulgaris.

PMID- 9520035
TI  - Recalcitrant pyoderma gangrenosum: treatment with thalidomide.

PMID- 9520036
TI  - Basal cell carcinoma arising in a sternotomy scar: a report of three cases.

PMID- 9520038
TI  - Carcinoma of the lip in kidney transplant recipients.

PMID- 9520037
TI  - Adnexotropic T-cell lymphoma presenting with generalized anhidrosis, progressive
      alopecia, pruritus, and Sjogren's syndrome.

PMID- 9520039
TI  - Nonpigmenting solitary fixed drug eruption caused by pseudoephedrine
      hydrochloride.

PMID- 9520040
TI  - Pilotropic mycosis fungoides.

PMID- 9520041
TI  - Follicular mycosis fungoides.

PMID- 9520042
TI  - Adverse reactions of topical capsaicin.

PMID- 9520043
TI  - Squamous cell carcinoma of the penis.

PMID- 9520044
TI  - Treatment of palmoplantar eczema with bath-PUVA therapy.

PMID- 9520045
TI  - Surgical treatment of acquired external auditory canal atresia.
AB  - OBJECTIVE: This study aimed to analyze the etiologies, clinical presentation,
      treatment options, and results of treatment in a series of patients with acquired
      external auditory canal atresia (AEACA) and to put this analysis in the context
      of the existing literature on this topic. STUDY DESIGN: The study design was a
      retrospective case review. SETTING: The study was performed at a tertiary
      otologic referral practice. PATIENTS: This study included patients with soft
      tissue AEACA. INTERVENTION: Patients received surgical excision of atresia
      process, conchomeatoplasty, canalplasty, and, when indicated, split-thickness
      skin graft (STSG) reconstruction. MAIN OUTCOME MEASURES: These included
      definition of a characteristic patient profile and the incidence of postoperative
      complications including restenosis. RESULTS: This series of six patients is
      unusual in that in all patients, atresia resulted either from prior surgery or
      trauma rather than from chronic infection, which is the most commonly seen
      etiology in the literature. An average of 14 years' lag time transpired between
      the inciting event and the surgical repair. Five of six patients required STSG
      for reconstruction; all did well. The single patient who did not require STSG had
      a minor restenosis develop that did not require revision surgery. CONCLUSIONS:
      Acquired external auditory canal atresia often is caused by trauma or prior
      surgery. Years may elapse between the inciting event and reconstructive surgery.
      The use of an STSG can be an important component to a successful surgical
      outcome.

PMID- 9520046
TI  - Cause of posterior canal wall retraction after surgery from the viewpoint of
      mastoid conditions.
AB  - OBJECTIVE: To determine the relationship between preservation of the mastoid
      mucosa during ear surgery and retraction of the attic or posterior wall of the
      external auditory canal (EAC) and mastoid aeration after surgery. METHODS AND
      DESIGN: Retraction of the posterior EAC wall and mastoid aeration were evaluated
      after surgery in 48 individuals (50 ears) with cholesteatoma, adhesive otitis
      media, or chronic suppurative otitis media, in whom the posterior bony EAC walls
      were removed with or without preservation of mucosa and reconstructed with soft
      tissues alone (EAC skin and temporal fascia) during surgery. RESULTS:
      Postoperative computed tomography showed that in ears with notable retraction of
      the posterior EAC wall appearing like an open mastoid cavity, there was no air in
      the mastoid, whereas in ears with no or only slight retraction there was computed
      tomographic evidence of mastoid aeration. Second, notable retraction of the
      posterior EAC wall occurred in a significantly smaller percentage of ears in
      which at least the epitympanic mucosa had been able to be preserved during
      surgery than in those that had undergone removal of all mucosa (mastoidectomy).
      CONCLUSIONS: These results indicate that 1) preservation of epitympanic mucosa
      during surgery is an important factor for prevention of retraction of the
      posterior EAC wall and for reaeration of the mastoid after surgery, and 2) the
      intact canal wall technique seems to be indicated whenever at least the
      epitympanic mucosa can be preserved, and when no mucosa can be preserved the
      canal wall down procedure seems to be indicated.

PMID- 9520047
TI  - Prognostic factors in tympanoplasty.
AB  - OBJECTIVE: To assess the prognostic value of pathologic and technical variables
      influencing the functional outcome of tympanoplasty. PATIENTS AND STUDY DESIGN:
      Retrospective review of the records of 544 patients affected by chronic otitis
      with or without cholesteatoma, operated on by the senior author in a city
      hospital ENT department. Follow-up was provided systematically by the same
      institution. INTERVENTIONS: These included tympanoplasty without mastoidectomy in
      339 cases, canal wall up technique in 134 cases, and canal wall down in 71 cases.
      Three hundred twenty-six (60%) were primary, and 218 (40%) were revision
      procedures. Myringoplasty was performed with autologous temporalis fascia,
      ossiculoplasty with incus interposition, or partial or total ossicular
      prostheses. Mean follow-up was 14 months (range, 12-50 months). MAIN OUTCOME
      MEASURES: Hearing results were defined according to the Committee on Hearing and
      Equilibrium Guidelines. A one-way analysis of variance was used to determine
      group differences. Multiple logistic regression analysis was subsequently carried
      out on the different pathology groups via the hierarchical log linear model. A
      probability value of p < 0.05 was the level of significance. RESULTS: The status
      of the mucosal lining, the mastoidectomy, the availability of the malleus handle,
      and the tympanic membrane perforation were all significantly predictive of the
      hearing outcome but with differing weight according to the pathologic condition.
      CONCLUSIONS: Anatomic and technical factors diversely affect the functional
      outcome of tympanoplasty. A better knowledge of their predictive roles and
      weights may be useful in both the surgeon's judgment and in the information given
      to the patient.

PMID- 9520048
TI  - Irradiated rib cartilage graft for reconstruction of the tympanic membrane:
      preliminary results.
AB  - OBJECTIVE: To evaluate the advantages, disadvantages, safety, and results in
      reconstruction of the tympanic membrane using irradiated rib cartilage. STUDY
      DESIGN: Retrospective chart review. SETTING: A tertiary referral center.
      PATIENTS: All patients who had > or =6 months follow-up who underwent
      tympanoplasty or tympanomastoidectomy using irradiated rib cartilage graft at our
      institution from January 1, 1993 to December 31, 1996. INTERVENTION:
      Tympanoplasty or tympanomastoidectomy using homologous irradiated rib cartilage
      as graft material. MAIN OUTCOME MEASURES: Postoperative speech reception
      thresholds, speech discrimination scores, and air-bone gap were compared with
      preoperative levels. Complications directly related to irradiated rib cartilage
      tympanoplasty were sought. RESULTS: Speech reception threshold did not
      significantly change. Speech discrimination scores were stable or improved in all
      patients. Postoperative air-bone gap was < or =10 dB in 43.2% of patients and <
      or =20 dB in 70.3% of patients. There was a 16% complication rate regarding
      tympanoplasty in general. No complications unique to irradiated rib cartilage
      occurred. CONCLUSION: Irradiated rib cartilage is an alternative tympanoplasty
      material that may save operating time, spares patients an added incision,
      provides results similar to other grafting material, and is safe.

PMID- 9520049
TI  - Endolymphatic sac occlusion for the enlarged vestibular aqueduct syndrome.
AB  - OBJECTIVE: To test the efficacy of occlusion of the enlarged vestibular aqueduct
      to treat the progressive sensorineural hearing loss associated with the enlarged
      vestibular aqueduct (EVA) syndrome. STUDY DESIGN: Prospective controlled study.
      SETTING: Tertiary care referral center. PATIENTS: Sixteen consecutive patients
      (29 affected ears) with progressive sensorineural hearing loss and vestibular
      aqueducts >1.5 mm in diameter without other inner ear anomalies participated in
      this study. INTERVENTION: In 10 patients with progressive hearing loss, the EVA
      was occluded in the ear with worse hearing by placing a fascia graft between the
      posterior fossa dura overlying the endolymphatic sac and intraosseous duct and
      the posterior semicircular canal without opening the endolymphatic sac. In the
      operative ears, serial postoperative audiograms were compared with the
      contralateral ear in patients with bilateral EVA and with the other nonoperated
      control ears. MAIN OUTCOME MEASURES: The rate of decline of pure-tone average and
      speech discrimination before surgery in the operated ear was compared with the
      rate of decline postoperatively in the same ear. The rates of decline in the
      nonoperated contralateral ear from the same patient and the nonoperated control
      ears from other patients were also used for comparison with the postoperative
      rate of decline in the operated ears. RESULTS: There was no statistically
      significant change in the rate of hearing loss in patients undergoing occlusion
      of the EVA. CONCLUSIONS: Extraluminal soft-tissue occlusion of the EVA appears to
      be a safe procedure but has not yet been shown to be significantly effective in
      altering the sensorineural hearing loss accompanying the EVA syndrome. Further
      surgical intervention does not appear warranted until such time that longitudinal
      follow-up shows sufficient evidence of efficacy of the procedure.

PMID- 9520050
TI  - Speech recognition performance of older children with cochlear implants.
AB  - HYPOTHESIS: The primary purpose of this study was to determine if children, > or
      =5 years old, with onset of deafness before the acquisition of spoken language
      (i.e., prelingually deafened) derived more benefit from multichannel cochlear
      implants than from conventional hearing aids. It was hypothesized that children
      who used oral communication (speech plus listening) would demonstrate higher
      levels of performance after implantation than children who used total
      communication (English sign system plus speech and listening). BACKGROUND:
      Previous research suggests that prelingually deafened children given implants at
      an older age derive limited benefit from these devices. Changes in candidacy
      criteria and advances in technology, however, may make cochlear implants a more
      viable treatment option for this group of patients. METHODS: A repeated-measures
      design was to used to compare patients' preoperative performance with hearing
      aids to postoperative performance with the CLARION cochlear implant after 3 and 6
      months of device use. Pre- and postoperative performance were analyzed separately
      for children who used oral and total communication. RESULTS: Both groups of
      children (oral and total communication) demonstrated significant postoperative
      improvement on all outcome measures over time. Postoperative scores of the
      children who used oral communication were significantly higher than those of the
      children who used total communication on four of the five outcome measures.
      CONCLUSIONS: Prelingually deafened children who do not receive cochlear implants
      until > or =5 years of age derive significant benefit from current implant
      devices compared with that obtained with conventional hearing aids. The greatest
      benefit is derived by children who use oral communication, with much more limited
      benefit demonstrated by children who use total communication.

PMID- 9520051
TI  - Cochlear implantation in children younger than 2 years old.
AB  - OBJECTIVE: To determine the viability of giving implants to children <2 years old
      and to assess the development of speech perception. STUDY DESIGN: A prospective
      study with a follow-up period of 1-5 years. SETTING: New York University Medical
      Center. PATIENTS: The patients consisted of 11 consecutive profoundly deaf
      children, aged 14-23 months, who were given the Nucleus cochlear implant.
      METHODS: Closed- and open-set speech perception were assessed preoperatively and
      postoperatively using the following measures: Early Speech Perception (ESP) test,
      the Northwestern University children's perception of speech test (NU-CHIPS), the
      Glendonald auditory screening procedure (GASP) word and sentence tests, the
      phonetically balanced kindergarten (PBK) word test, common phrases test, the
      multisyllabic lexical neighborhood test (MLNT), and the lexical neighborhood test
      (LNT). RESULTS: Paired t test was used to examine changes in scores from the
      preoperative test interval to the last available postoperative assessment.
      Results indicate that all patients had significant improvement from preoperative
      performance to the last postoperative evaluation and were using oral language as
      their means of communication. There were no medical or surgical complications.
      CONCLUSIONS: Children <2 years old receive substantial benefit from a
      multichannel cochlear implant with no increase in risk when compared with older
      children.

PMID- 9520053
TI  - Dose-related vestibular and cochlear effects of transtympanic gentamicin.
AB  - HYPOTHESIS: To test the relative dose-related cochlear and vestibular ototoxicity
      produced by transtympanically injected gentamicin in the Mongolian gerbil.
      BACKGROUND: Transtympanic gentamicin is gaining favor as a relatively noninvasive
      treatment for Meniere's disease (MD). Few basic science studies exist regarding
      the vestibular and cochlear toxicities and dosage and administration schedules,
      however. The absence of standardized procedures and use of different species as
      animal models may account for the variable outcomes and lack of agreement found
      in the literature. METHODS: Histologic evaluation was performed on inner ears
      from Mongolian gerbils to study vestibular and cochlear damage. Comparisons were
      made between animals receiving single (1x) and five (5x) daily injections of
      gentamicin/gelfoam slurry and similarly injected (saline/gelfoam) and noninjected
      controls. RESULTS: Two weeks after injection, qualitative and quantitative
      changes were seen in posterior cristae hair cells in the 1x and 5x gentamicin
      injected groups. Statistically significant decreases in hair cells were seen when
      5x injected ears were compared with 1x injected ears and when 1x injected ears
      were compared with control ears. When damage was observed in the posterior crista
      sensory cells, damage was also seen in cochlear hair cells. CONCLUSIONS: Our
      results suggest that in the gerbil, gentamicin is ototoxic but not selectively
      vestibulotoxic. In general, increasing the number of transtympanic injections
      increases the damage to sensory hair cells in both the posterior crista and the
      cochlea. A variation in interanimal susceptibility to ototoxic effects exists,
      but the amount of damage is consistent in both cochlear and vestibular hair cells
      from the same animal.

PMID- 9520052
TI  - Facial nerve stimulation from cochlear implants.
AB  - OBJECTIVE: To evaluate the incidence of facial nerve stimulation from cochlear
      implants and to better define the segment of nerve being stimulated and the
      causes of stimulation. STUDY DESIGN: Retrospective patient case review and a
      temporal bone dissection study. SETTING: A tertiary care setting. PATIENTS: All
      patients given a cochlear implant at the Hospital of the University of
      Pennsylvania. This encompassed only adult patients. INTERVENTION: All patients
      had surgical insertion of either a 3M single channel, Nucleus 22-channel, or
      CLARION multichannel cochlear implant. MAIN OUTCOME MEASURES: Demonstration of
      facial nerve stimulation with a cochlear implant and determination of affected
      electrodes; measurement of electrode location and distances between the
      labyrinthine segment of the facial nerve and the cochlea in temporal bone
      dissections: and determination of the relationship between the labyrinthine
      facial nerve and the cochlea using computed tomography evaluation. RESULTS: The
      overall incidence of facial nerve stimulation using all three devices was 14% (8
      of 58). Otosclerosis and otosyphilis appear to be predisposing conditions to
      stimulation. The mid-cochlear electrodes, located near the labyrinthine facial
      nerve, appear to cause stimulation of the VIIth nerve most commonly. Computed
      tomographic evaluation of the bone between the labyrinthine fallopian canal and
      the cochlea may provide some indication of potential facial nerve problems.
      CONCLUSION: Facial nerve stimulation from the use of cochlear implants is more
      prevalent in patients with otosclerosis and otosyphilis. The labyrinthine segment
      of the facial nerve is the most likely area being stimulated in most patients.
      Preoperative computed tomographic evaluation may be beneficial in determining the
      possibility of this problem.

PMID- 9520054
TI  - Three-dimensional eye movement analysis during caloric stimulation used to test
      vertical semicircular canal function.
AB  - HYPOTHESIS AND BACKGROUND: Quantitative caloric testing is considered to be one
      of the most sensitive parameters in the diagnosis of peripheral vestibular
      disorders. In the past, because of limitations in the methods, the evaluation of
      the caloric response was restricted to mainly lateral semicircular canal
      functions. In this study, the authors tried to extend caloric testing to the
      function of all semicircular canals by using three-dimensional (3-D) analysis
      techniques. METHODS: The authors studied in seven normal subjects 3-D eye
      movement responses to air caloric of the right ear with the subjects positioned
      in standard caloric position (lateral semicircular canal vertical) or such that
      one of the three semicircular canals of the right side was horizontal. Movement
      of the left eye was measured in 3-D with a dual-magnetic search coil. During
      stimulation, 10 seconds of maximum response were selected and desaccaded to yield
      the slow-phase velocity profile. From this profile, the average magnitude and
      direction of the eye rotation axis (velocity vector) were calculated in head
      coordinates. RESULTS: In all subjects, in standard caloric position, warm caloric
      produced eye velocity vectors that clustered closely along the direction expected
      from an excitation of the right lateral semicircular canal. When the subjects
      were positioned with one of the vertical semicircular canals horizontal, the
      orientation of the velocity vectors shifted toward a direction expected from the
      combined excitation of the lateral and the other vertical semicircular canal and
      vice versa. CONCLUSIONS: The 3-D eye movement recordings during caloric
      stimulation in different head positions allow the evaluation of the function of
      all semicircular canals.

PMID- 9520055
TI  - Vestibular decruitment, hyperactivity, and rebound caloric nystagmus.
AB  - OBJECTIVE: This study examined the collective sensitivities of decruitment,
      hyperactivity, and rebound caloric nystagmus (RCN) for lesions of the brain
      stem/cerebellum against the current gold standard of imaging, the contrast
      enhanced magnetic resonance imaging (MRI). STUDY DESIGN: This is a retrospective
      study of patients who underwent a vestibular evaluation and a contrast-enhanced
      MRI scan. SETTING: The study was performed at a tertiary referral center.
      PATIENTS: The patients included in this study were evaluated for investigation of
      a variety of reported problems, including vertigo/dysequilibrium, headache,
      hearing loss, and tinnitus. Their age range was 13 to 79 years. INTERVENTION:
      Every patient underwent a vestibular evaluation, which included the Torok
      monothermal caloric test and an MRI scan. MAIN OUTCOME MEASURES: The results of
      this caloric test include vestibular decruitment, hyperactivity, and rebound
      caloric nystagmus. The sensitivity and specificity of these results for MRI
      confirmed brain stem/cerebellar lesions were determined. RESULTS: The overall
      sensitivity of the measures of this caloric test was 90%. The overall specificity
      was 25%. CONCLUSIONS: As a screening test for brain stem cerebellar lesions, the
      Torok monothermal caloric test performs well in terms of its sensitivity. The
      specificity is low, and this probably because MRI looks at morphology rather than
      function.

PMID- 9520056
TI  - Dexamethasone inner ear perfusion for the treatment of Meniere's disease: a
      prospective, randomized, double-blind, crossover trial.
AB  - OBJECTIVE: To investigate the benefits of intratympanic administration of
      dexamethasone in the treatment of unilateral Meniere's disease, with particular
      attention to the symptoms of hearing loss and tinnitus. STUDY DESIGN: A
      prospective, randomized, double-blind, crossover study comparing improvements in
      hearing loss, tinnitus, aural fullness, and caloric vestibular response secondary
      to intratympanic dexamethasone and sodium hyaluronate injection versus placebo
      consisting of saline and sodium hyaluronate. SETTING: A private
      otology/neurotology practice. PATIENTS: Twenty patients diagnosed with either
      definite or probable Meniere's disease as defined by the American Academy of
      Otolaryngology Head and Neck Surgery Committee on Hearing and Equilibrium. All
      patients were < or =21 years old and were not receiving any other form of
      treatment for their Meniere's disease. Each patient's primary symptoms of concern
      were hearing loss, aural fullness, and roaring tinnitus. INTERVENTIONS: Three
      consecutive daily administrations of intratympanic dexamethasone or placebo to
      the involved ear. MAIN OUTCOME MEASURES: Changes in audiometric pure-tone
      averages, speech reception thresholds, caloric vestibular responses, scores on
      the tinnitus handicap inventories, questionnaires, and telephone interview
      responses. RESULTS: No significant changes were observed in any measured
      parameter. Patients were unable to consistently identify which medication was
      dexamethasone and which was placebo. CONCLUSIONS: Intratympanic administration of
      dexamethasone in a group of patients with unilateral Meniere's disease (Shea's
      stage IV) showed no benefit over placebo for the treatment of hearing loss and
      tinnitus.

PMID- 9520057
TI  - Direct cochlear nerve monitoring: first report on a new atraumatic, self
      retaining electrode.
AB  - OBJECTIVE: To assess the efficacy and safety of a new atraumatic, self-retaining
      cranial nerve electrode for direct cochlear nerve monitoring during
      cerebellopontine angle surgery. STUDY DESIGN: Prospective clinical investigation.
      SETTING: The Skull Base Surgery Center at Kaiser Permanente, San Diego, a
      tertiary referral center for neurotologic and skull-base surgery within Southern
      California Permanente Medical Group. PATIENTS: Eighteen patients, with aidable
      preoperative hearing, underwent direct cochlear nerve monitoring with this new
      electrode during cerebellopontine angle surgery for a variety of diagnoses.
      METHODS: Intraoperative observations of cochlear nerve action potential amplitude
      and latency were recorded. Preoperative and 1-month postoperative audiograms were
      compared to assess the degree of hearing preservation. Postoperative facial nerve
      function was assessed using the House-Brackmann method. RESULTS: Good auditory
      function was preserved in four of eight acoustic tumors, with poor hearing
      preserved in two additional patients. Good auditory function was preserved in the
      remaining ten patients. Cochlear nerve action potential amplitudes between 5 and
      70 microV were recorded. Postoperative facial nerve function was House-Brackmann
      class I-II in all 18 patients. CONCLUSION: The authors find this new electrode to
      be safe and effective for monitoring cochlear nerve function during
      cerebellopontine angle surgery.

PMID- 9520058
TI  - Technical refinements in retraction for middle fossa surgery.
AB  - OBJECTIVE: This report describes an alternative technique for exposure of the
      floor of the middle fossa. STUDY DESIGN: Descriptive review of alternative middle
      fossa retraction techniques on a retrospective case series. SETTING: Tertiary
      referral center. PATIENTS: Patients undergoing middle fossa or combined petrosal
      craniotomy were studied. INTERVENTIONS: Dural elevation was carried anteriorly
      past the middle meningeal artery to permit separation of the dura from connective
      tissue over the Gasserian ganglion. With the dural release, flexible spatula
      retractors (Fukushima) can be used. RESULTS: The advantages of this technique are
      1) this system is "low profile," with the back of the retractor posing no
      obstruction to vision or angle of instrument manipulation; 2) the anterior dural
      release permits extensive exposure with less force than is necessary when dural
      attachments to the trigeminal nerve remain intact; and 3) anterior exposure of
      the clivus and petrous apex is achieved without the need for transection of V3
      (3rd division fifth cranial nerve). CONCLUSIONS: The authors find these
      refinements of practical benefit for breadth of exposure, visibility, and room
      for instrumentation during middle fossa surgery.

PMID- 9520059
TI  - Acoustic neuromas presenting with normal or symmetrical hearing: factors
      associated with diagnosis and outcome.
AB  - OBJECTIVE: To evaluate the clinical features leading to diagnosis in patients
      with acoustic neuroma (AN) who present with normal or symmetrical hearing.
      Underlying tumor characteristics are also studied to identify a possible
      explanation for this unique presentation in the AN population. STUDY DESIGN:
      Retrospective case review comprising patients who were identified as having AN
      that presented with normal audiometry. SETTING: A tertiary referral center.
      PATIENTS: Patients with AN who met the criteria for normal were included in the
      report. For this study, abnormal audiometry is defined as an interaural
      difference of > or =15 dB at a single frequency or > or =10 dB at two or more
      frequencies, and an interaural speech reception threshold difference of > or =20
      dB, or a speech discrimination score of > or =20%. MAIN OUTCOME MEASURES:
      Presenting symptoms and signs, clinical features that led to the diagnosis of AN,
      auditory brain stem response results, tumor location, size and relationship to
      temporal bone landmarks, surgical intervention, surgical outcome, and results of
      hearing preservation attempts were tabulated for each patient. RESULTS: A total
      of 29 patients (5%) were identified who had normal or symmetrical pure-tone
      audiograms between 500 and 4,000 Hz. The average difference in speech reception
      threshold between tumor and nontumor ear was 3.2 dB, and the average difference
      in speech detection score was 2.6%. The most common presenting symptoms that led
      to the diagnosis of the AN were dysequilibrium/vertigo (12 cases), cranial nerve
      V and VII abnormalities (11 cases), routine screening for families with
      neurofibromatosis type 2 (5 cases), asymmetrical tinnitus (4 cases), headaches (4
      cases), unilateral subjective hearing difficulty (4 cases), and incidental
      finding during evaluation for another problem (4 cases). The average tumor size
      was 19 mm, with five cases presenting with tumors of size > or =30 mm. Nineteen
      patients underwent a hearing preservation procedure (middle fossa or
      retrosigmoid), 11 of whom had useful hearing postoperatively. CONCLUSIONS:
      Despite normal audiometry, patients presenting with imbalance or vertigo, Vth or
      VIIth cranial nerve deficits, or unilateral hearing complaints may warrant
      further evaluation to rule out the possibility of AN or other retrocochlear
      lesion. To seek an explanation for this phenomenon, the incidence of various
      tumor characteristics (e.g., depth of penetration into the internal auditory
      canal and degree of porous erosion) is discussed and compared with the entire AN
      population.

PMID- 9520061
TI  - Auditory brain stem response in young and old guinea pigs.
AB  - OBJECTIVE: To characterize age-related auditory changes in genetically similar
      guinea pigs. BACKGROUND: In humans and animals, changes in hearing are known to
      occur with age. METHODS: Brain stem-evoked responses were measured in genetically
      similar guinea pigs that ranged 6-36 months in age. Changes in hearing and the
      input/output function curve were determined. RESULTS: Threshold shift with
      increase in age was seen. Marked reduction in amplitude of response with
      increasing age was also demonstrated. No change was seen in latency or interpeak
      interval. CONCLUSIONS: In genetically similar guinea pigs, age-related changes in
      threshold occurred. Latency and interpeak intervals remained unchanged. Amplitude
      of response decreased substantially after 12 months of age to a greater extent
      than predicted by threshold shifts alone. This phenomenon appears important in
      understanding the pathophysiology of age-related hearing loss.

PMID- 9520060
TI  - Petrous apex lesions.
AB  - OBJECTIVE: The accurate diagnosis of different petrous apex lesions is
      increasingly common as a result of modern imaging techniques, combining computed
      tomography and magnetic resonance imaging. The clinical features, diagnostic
      evaluation, imaging, and treatment outcomes of patients with petrous apex lesions
      are reviewed. STUDY DESIGN: Retrospective case review. SETTING: Private practice
      tertiary otologic referral center. PATIENTS: Sixty-six patients treated at the
      House Ear Clinic in the last 2 decades for a lesion of the petrous apex. Lesions
      included cholesterol granuloma, cholesteatoma, and chondrosarcoma, among others.
      Mean follow-up time was 27 months and ranged from 1 month to 10 years.
      INTERVENTION(S): Cholesterol granulomas were treated with drainage procedures,
      solid tumors were surgically removed using primarily the middle fossa or
      infratemporal fossa approaches. RESULTS: The most common presenting symptoms were
      hearing loss, dizziness, headaches, and tinnitus. Decreased cranial nerve V
      function was present in 22%. The most common cystic lesion was cholesterol
      granuloma, which constituted 60% of all lesions in the study, followed by
      cholesteatoma (9%). Chondrosarcomas were the most common solid lesion (6% of all
      lesions). Asymmetric pneumatization and retained secretions give radiographic
      findings commonly overdiagnosed as lesions of the petrous apex. CONCLUSIONS:
      Lesions of the petrous apex can be diagnosed accurately by CT and MRI and can be
      divided into cystic and solid lesions. Cholesterol granulomas are by far the most
      common lesion found in this site and can be drained with minimal morbidity via
      the infracochlear approach. Solid tumors may require extensive exposure and a
      combined skull base approach for complete removal.

PMID- 9520062
TI  - Effect of transtympanic injection of steroids on cochlear blood flow, auditory
      sensitivity, and histology in the guinea pig.
AB  - HYPOTHESIS: Transtympanic application of steroids is not harmful to the inner
      ear. BACKGROUND: Steroids are routinely used to treat inner ear pathologies, such
      as sudden sensorineural hearing loss and autoimmune inner ear disease. The
      transtympanic route has received increased attention as it can lead to higher
      levels in tissue and nearly eliminate systemic effects. There has been concern
      over the safety of applying these drugs directly to the inner ear. METHODS: This
      study investigates the effects of transtympanic Dexamethasone injection on
      cochlear blood flow using laser Doppler flowmetry, auditory sensitivity using
      auditory brain stem responses, and histology in the guinea pig. RESULTS: Results
      show a significant increase in cochlear blood flow within 30 s to a mean of
      29.26% without significant change in auditory sensitivity. The increase in
      cochlear blood flow was sustained and did not return to baseline for at least 1
      hour after drug application. No histologic changes were observed. CONCLUSIONS:
      These results suggest that transtympanic steroid application is not likely to be
      detrimental to the inner ear. Additionally, the increase in blood flow may
      indicate a possible mechanism accounting for the pharmacologic effects of
      steroids in the inner ear.

PMID- 9520063
TI  - Facial nerve surgery in the 19th and early 20th centuries: The evolution from
      crossover anastomosis to direct nerve repair.
AB  - The historical aspects of facial nerve (FN) anatomy and of Bell's palsy have long
      been favorite topics of otologic historians. Little attention has been paid,
      however, to the evolution of FN surgery, a subject with a remarkably rich and
      engaging history. In the early 13th century, Roland, an Italian surgeon, used a
      red hot iron to coapt severed nerve endings. In the 17th century, Ferrara,
      another Italian, sutured injured nerves with tortoise tendon dipped in hot red
      wine. It was not until the late 19th century that peripheral nerve suture became
      a subject of serious scientific study. Although it is ironic, the course of
      events suggests that the evolution of FN repair was greatly stimulated by the
      development of the modern mastoid operation. Whereas the simple mastoid operation
      practiced by Wilde (1853) and others carried little risk of FN injury, more
      adventuresome procedures such as radical mastoidectomy (Kessel, 1885) carried a
      much greater risk. The abundance of iatrogenic palsies during this era
      undoubtedly did much to motivate surgeons to seek a better means of restoring
      facial animation. Most surgeons would be surprised to learn that crossover
      anastomoses predated direct nerve repair by nearly half a century. In 1879, the
      German surgeon Drobnik performed the first facial-spinal accessory anastomosis.
      Over the next two decades, numerous articles were written (most notably by Sir
      Charles Balance and Harvey Cushing) on crossovers between the FN and cranial
      nerves IX, X, XI, and XII. Although a few tentative attempts at reapproximating
      severed FNs took place in the first two decades of this century, it was not until
      1925 that an actual suture repair of an intratemporal injury was undertaken. This
      feat was first accomplished by the famous hand surgeon Sterling Bunnell and
      shortly thereafter by the otolaryngologist Robert Martin. The evolution of FN
      surgery in the days predating the operating microscope is a rich tapestry of
      colorful personalities and clashing egos, which saw promising advances relegated
      to obscurity and some previously obscure techniques become progressively more
      promising.

PMID- 9520064
TI  - Imaging case of the month: translabyrinthine schwannoma.

PMID- 9520065
TI  - Surgical anatomy of the transtemporal approaches to the petrous apex.

PMID- 9520066
TI  - Functional evaluation techniques in mitochondrial disorders.
AB  - Most of the mitochondrial disorders affect the brain and muscle metabolism with
      variable degrees of impairment. The diagnostic usefulness of the following
      physiological and imaging methods, which also offer functional information that
      can be used for follow-up, is critically assessed: lactate levels, exercise
      testing, phosphorus magnetic resonance spectroscopy (MRS), proton MRS, functional
      magnetic resonance imaging, positron emission tomography, optical tissue oximetry
      and single photon emission tomography. Knowledge of the advantages, shortcomings
      and results of each method in the evaluation of mitochondrial diseases is
      mandatory before they can be applied to other disorders with suspected oxidative
      impairment.

PMID- 9520067
TI  - The lateralizing value of ictal clinical symptoms in uniregional temporal lobe
      epilepsy.
AB  - In order to assess the lateralizing value of several ictal and postictal clinical
      symptoms in temporal lobe epilepsy (TLE), we analyzed 89 seizures of 20 left
      dominant patients with intractable left (n = 9) versus right (n = 11) TLE who had
      undergone successful anterior temporal lobectomy. In left TLE, movement arrest at
      seizure onset, postictal dysphasia > 120 s and postictal dyslexia > 180 s were
      the most typical findings and associated with a sensitivity of 94, 94, and 100%,
      respectively. The highest specificity of 100% each was evident for contralateral
      versions of eyes and head and dystonic posturing. In right TLE, the highest
      sensitivity was seen for whole-body movements at seizure onset, postictal
      dysphasia < 120 s and postictal dyslexia < 180 s with figures of 82, 87, and 93%,
      respectively. As compared to left TLE, contralateral version and dystonic
      posturing, ictal speech, and postictal dyslexia < 180 s each had a specificity of
      100%. The careful combined analysis of certain ictal clinical signs combined with
      consistent findings of interictal EEG and neuroimaging studies may be often
      sufficient to proceed with epilepsy surgery without invasive recordings even if
      ictal scalp EEG is not unambiguous.

PMID- 9520068
TI  - White matter changes on CT and MRI: an overview of visual rating scales. European
      Task Force on Age-Related White Matter Changes.
AB  - Since the recognition of white matter changes on CT (leukoaraiosis), rating
      scales for the location and severity of white matter changes have been developed,
      mainly for research purposes, to investigate factors such as the relation with
      cognition, risk factors, and pathology. The main purpose of rating scales is to
      provide scores that can be used in statistical analyses. The development of the
      NINDS-AIREN criteria for vascular dementia have introduced a new application for
      these rating scales in investigating and delineating the amount of white matter
      changes on CT/MRI sufficient to fulfill the criteria. Furthermore, in Alzheimer's
      disease, recognition of white matter changes may serve to delineate homogeneous
      groups and help to identify patients with different symptomatology. We reviewed
      the existing rating scales for CT and MRI and judged their properties and
      reliability. The ideal rating scale does not yet exist, but different rating
      scales may serve different purposes, for which some recommendations are made.

PMID- 9520069
TI  - Progressive loss of speech: a neuropsychological profile of premotor dysfunction.
AB  - Several patients with 'progressive loss of speech output' or 'progressive
      anarthria' of degenerative origin have been reported in the literature. We report
      5 clinical cases with slowly progressive loss of speech output and initially no
      deficit in other cognitive domains. The early clinical features were analysed in
      an attempt to identify the anatomo-functional systems implied in the degenerative
      process. The first phase of the disorder was characterised by impaired
      articulation consistent with speech apraxia, telegraphic style and a difficulty
      to elaborate a series of orofacial or hand movements. It is argued that these
      symptoms result from an impairment of complex motor processing due to dysfunction
      of the ventral premotor system. In the second phase, a decrease in spontaneous
      speech and self-initiated action was combined with exaggerated dependency on
      external stimuli, interpreted as dysfunction of the dorsal premotor system. We
      suggest that the neuropsychological profile of the disorder may result from
      progressive degeneration of the premotor cortex.

PMID- 9520070
TI  - Hypertrophy of the inferior olivary nucleus in patients with progressive
      supranuclear palsy.
AB  - Hypertrophic changes in the inferior olivary nuclei have been occasionally
      described in patients with progressive supranuclear palsy (PSP). To elucidate the
      incidence of olivary hypertrophy, we investigated morphologically the olives and
      their associated pathways in 20 autopsied cases: 11 cases of PSP, 3 cases of
      Machado-Joseph disease and 6 cases of dentatorubropallidoluysian atrophy (DRPLA)
      as control diseases that usually exhibited lesions of the cerebellofugal pathway.
      Olivary hypertrophy was observed in 5 of 11 PSP cases, but not in the other
      diseases, except for 1 case of DRPLA with an old infarct in the dentate nucleus.
      In the olivopetal pathway, grumose degeneration of the dentate nucleus and mild
      neuronal loss in the red nucleus were observed in all patients with PSP and in
      the control subjects. Atrophy and fibrillary gliosis of the tegmentum of the
      pons, including that of the bilateral central tegmental tracts, were observed in
      all patients with PSP, more severe in the cases with hypertrophic neurons in the
      olives. We speculate that a lesion that involves the central tegmental tracts may
      play a major role in inducing hypertrophy of the olives in patients with PSP.

PMID- 9520071
TI  - Antiganglioside GM1 antibodies and their complement activating capacity in
      central and peripheral nervous system disorders and in controls.
AB  - So far, the pathogenic significance and use for diagnosis of antiganglioside GM1
      antibodies (anti-GM1) are unclear. We therefore compared serum IgM and IgG
      antimonosialo ganglioside GM1 levels of 33 patients with presumed immune-mediated
      neuropathies, 100 patients with various other central or peripheral neurological
      disorders, and 110 controls by ELISA. We also measured the complement-activating
      capacity of anti-GM1 by C5b-9-GM1-ELISA to evaluate its value to distinguish
      between pathogenic and nonpathogenic autoantibodies. Low levels of anti-GM1 were
      observed in all disease categories and in controls (healthy blood donors). Twenty
      four of the controls including the 10 with the highest serum IgM or IgG anti-GM1
      were examined for neurological disorders in a double-blind checkup study. In the
      patients, elevated IgM anti-GM1 levels were predominantly found in those with
      neuropathies (NP), but barely in patients with central nervous system disease
      (CNSD). We found elevated IgG anti-GM1 levels predominantly in patients with NP
      of inflammatory origin (multifocal motor neuropathy, chronic inflammatory
      demyelinating polyneuropathy or Guillain-Barre syndrome), rarely in patients with
      NP of noninflammatory origin or CNSD, but not in the control disease group
      myasthenia gravis (MG). Median levels of IgM-, IgG-, (IgM+IgG)-, and C5b-9
      binding anti-GM1 were significantly higher in patients with inflammatory NP as
      compared to the controls (p < 0.025). In addition, median levels of IgG- and
      (IgM+IgG)-anti-GM1 were significantly higher in inflammatory NP versus CNSD.
      Elevated complement-binding activity was associated with low or elevated IgM
      and/or IgG anti-GM1. Nevertheless, there was a significant correlation between
      anti-GM1 level (IgM+IgG) and the respective complement-activating capacity (r =
      0.758; n = 243). Estimation of anti-GM1 and their respective complement
      activating capacity may be helpful in the diagnosis of inflammatory neuropathies.
      However, neither an elevated anti-GM1 level nor an increased C5b-9 binding seems
      specific for a given disease category (e.g. peripheral nerve disease) nor a
      disease process (e.g. demyelination or inflammation).

PMID- 9520072
TI  - Cerebrospinal fluid levels of amyloid precursor protein and amyloid beta-peptide
      in Alzheimer's disease and major depression - inverse correlation with dementia
      severity.
AB  - Alzheimer's disease (AD) is the most common neurodegenerative disorder
      characterized by progressive dementia that ultimately leads to death.
      Histopathological hallmarks of AD include brain amyloid deposits and
      neurofibrillary tangles. Major depression is a frequent diagnosis in every
      gerontopsychiatric clinic that sees patients with both cognitive and affective
      disorders. Many depressed patients, in fact, are clinically characterized by
      cognitive impairments. Thus, an assay that excludes - or confirms - probable AD
      in cognitively impaired patients is desirable. Such assays may use protein
      markers that are derived from such histopathologically relevant molecules as the
      amyloid precursor protein (APP) and its derivatives including the amyloid beta
      peptides (Abeta). To evaluate the differential diagnostic properties of
      cerebrospinal fluid (CSF) Abeta and secreted soluble ectodomain (APPs), we
      quantitated CSF levels of these measures in AD patients and compared them to age
      matched control patients with major depression. CSF levels of APPs and Abeta were
      similar in patients with AD or major depression, and the apolipoprotein E
      genotype had no influence on CSF levels of Abeta in AD patients. Measurement of
      Abeta peptide using a novel zinc/copper capture ELISA that detects aggregated
      Abeta peptides as well demonstrated similar levels in AD and major depression. In
      AD patients, CSF levels of total Abeta (Abeta1-40 plus Abeta1-42) were inversely
      correlated with a functional measure of dementia severity (NOSGER), suggesting
      that CSF levels of Abeta decrease with advancing severity of AD. Thus, CSF levels
      of Abeta are not useful for the differentiation of AD from major depression.
      However, CSF levels of Abeta reflect the severity of dementia and may be useful
      as biological markers of the stage of the disease.

PMID- 9520073
TI  - Pharmacokinetic studies with a dual-release formulation of levodopa, a novel
      principle in the treatment of Parkinson's disease.
AB  - The objectives of the two studies reported here were the investigation of the
      influence of tablet breaking and food on the pharmacokinetics of levodopa and 3-O
      methyldopa (3-OMD) after administration of a new levodopa/benserazide formulation
      with a biphasic drug delivery profile (Madopar DR). Both studies had an open
      label, randomised, two-way crossover design and were conducted in 12 healthy
      young subjects. The pharmacokinetics of levodopa and 3-OMD after one intact or
      two halved tablets were very similar with average Cmax and tmax 1.9 mg x l(-1)
      and 1.2 h, respectively. Administration of the formulation after a standard
      breakfast did not influence the extent of levodopa absorption but increased the
      absorption rate. Cmax and tmax were on average 2.1 mg x l(-1) and 1.3 h,
      respectively, in the fed condition and 1.5 mg x l(-1) and 2.5 h in the fasted
      condition. The presence of food did not markedly affect the plateau in levodopa
      levels between about 1 and 3 h after intake. In conclusion, the release
      characteristics in healthy subjects of the new levodopa/benserazide formulation
      are influenced only to a minor extent by concomitant intake of food or by tablet
      breaking.

PMID- 9520074
TI  - MRI and 5-fluorouracil-levamisole chemotherapy.

PMID- 9520075
TI  - Odontoid osteomyelitis complicating pneumococcal pneumonia.

PMID- 9520076
TI  - Cell surface receptors. An introduction.

PMID- 9520077
TI  - The long-term outlook for hydrocephalus in childhood. A ten-year cohort study of
      155 patients.
AB  - Despite the fact that ventriculoperitoneal shunt insertion is the most commonly
      performed surgical operation in the pediatric neurosurgeon's repertoire, there is
      a surprising paucity of long-term outcome studies for these patients detailing
      either the complication rate over a predetermined time period or more importantly
      their intellectual outcome. The aims of this study, therefore, were to determine
      the 10-year outcome in a cohort of 155 children with shunted hydrocephalus, both
      in terms of the number and time sequence of shunt complications and also the long
      term academic (schooling) outcome of these individuals. This was a cohort study
      of 155 hydrocephalic children who underwent first-time ventriculoperitoneal shunt
      insertion between the years 1978 and 1983, who were then followed up on an annual
      outpatient basis for a period of 10 years or until death. Their academic records
      and the surgical morbidity and mortality encountered over the 10-year study
      period were used as the main outcome measures. For those children surviving until
      schoolage, 59% were able to attend a normal school. The academic outlook for
      those children with hydrocephalus secondary to infection (postmeningitic) or
      intraventricular hemorrhage was less favorable with 52 and 60% requiring special
      schooling compared to those children with congenital hydrocephalus (29%; p =
      0.036). 44% (68/155) of patients in this cohort did not require a shunt revision.
      The commonest reasons for shunt revision were blockage (49%) and infection (19%)
      which predominantly occurred within the first year of their original shunt
      procedure. Overall the infection rate was 12% (44/380 procedures). Furthermore an
      increased incidence of shunt infection was noted in those under 6 months old (p =
      0.040). There was an 11 % mortality during the 10-year follow-up period for those
      with nontumor-related hydrocephalus.

PMID- 9520078
TI  - Cerebellar infarction from a traumatic vertebral artery dissection in a child.
AB  - Infarction due to vertebral dissection is a rarely reported event in children. We
      describe the clinical presentation, radiological findings and surgical treatment
      of a child with cerebellar infarction resulting from a traumatic vertebral artery
      dissection. Review of the literature on stroke due to a vertebral artery
      dissection in the pediatric population shows that trauma is a common preceding
      event. Although the most common site of traumatic vertebral artery dissection is
      at C1-2 level, our case illustrates that the vertebral artery dissection may also
      involve the lower cervical segment. We emphasize that vertebral artery dissection
      should be considered in a child with acute symptoms and signs of posterior
      circulation ischemia and that MRI and MR angiography may be helpful in the
      diagnosis of infarction and vertebral artery dissection.

PMID- 9520079
TI  - Cranial vault moulding by the transcutaneous activation of implanted magnets.
AB  - The technique of distraction osteogenesis has not been widely used in the
      treatment of injuries of the head and face because of the need for external
      fixators. By using magnetic, rather than mechanical, forces to drive bone
      movement we hope to expand the applications of the technique to include the
      treatment of cranial vault deformities. Fifteen immature rabbits were studied.
      When they were 6 weeks old each had a magnet fixed to their left parietal bone. A
      head frame was attached and a magnet of either the opposite polarity to, (group
      1), or the same polarity as, (group 2), the implanted magnet was mounted on the
      frame. Five weeks later the rabbits were sacrificed. There were significant
      differences in parietal skull width and in several measures of skull length
      between the animals in group 1 and those in group 2. These results demonstrate
      that, in this model, magnetic forces can be used to modify skull growth.

PMID- 9520080
TI  - Cerebellar pontine angle ependymoma in infants.
AB  - We discuss the surgical approach used for and outcome in 11 infants (< or =3
      years) who were treated at our institution for ependymomas arising in the
      cerebellar-pontine (C-P) angle. The median age of the group was 19 months (range:
      6-26 months). Of these 11 patients, the initial surgery for 8 was performed at
      our center and achieved a gross total resection (GTR) in 4 patients and a
      subtotal resection (STR) in the remaining 4. The 3 patients who had tumor
      debulking performed elsewhere were subsequently referred to our institution and
      had definitive surgery after receiving 3-4 courses of chemotherapy; one of these
      children had a GTR, whereas the remaining 2 had an STR. During the immediate
      postoperative period, 9 patients had cranial nerve deficits that necessitated
      placement of a tracheostomy and a gastrostomy feeding tube; these were
      discontinued in 6 of the 9 patients as the deficits resolved. The majority of the
      permanent cranial nerve deficits involved the sixth and seventh cranial nerves.
      Of the 11 patients, 4 have died (progressive disease, n = 1; accidental death, n
      = 2; withdrawal of life support, n = 1); the remaining 7 patients are alive, with
      a median follow-up of 37 months (range: 20-73 months). Aggressive surgical
      resection for tumors arising in the C-P region is associated with postoperative
      deficits, which resolve over time with appropriate supportive care. This approach
      may increase the number of children in whom GTR is achieved, thereby potentially
      increasing the cure rate for these patients.

PMID- 9520081
TI  - Cavernous angiomas of the brain stem in children.
AB  - Out of 27 children with intracranial cavernous angiomas observed in a 17-year
      period of time, 3 presented with their lesion located in the brain stem. A
      further 19 pediatric cases of brain stem cavernous angiomas sufficiently well
      described for a reliable analysis were collected from the literature and
      evaluated for the present study. The widespread use of MR imaging has
      significantly increased the possibility of recognizing brain stem cavernomas at
      an early age; indeed, their incidence is nowadays regarded to range between 9 and
      15% of pediatric cavernous angiomas. A female predominance was noted in the
      present study. Focal neurological deficits are the most frequent presenting
      symptoms; they tend to occur acutely in most cases, although subsequent
      improvement may then be observed in several patients. Recurrent hemorrhages from
      the angioma result usually in heavier neurological signs. Surgical approaches
      have to be planned according to the location of the lesion, and to the site where
      the angioma is eventually in contact with the pial or ependymal surface. No
      surgical deaths were observed in these 22 children; only 2 patients presented a
      mild persistent worsening of their neurological status after the operation. These
      good results indicate that brain stem cavernous angiomas are actually a surgical
      lesion in spite of their apparently unfavorable location. The good prognosis is
      related to the anatomophysiological features of these lesions, which usually
      displace the brain stem structures rather than invade them, and are characterized
      by a low-pressure and slow blood flow circle.

PMID- 9520082
TI  - Choroid plexus papilloma and cysts in the Aicardi syndrome: case reports.
AB  - Two female infants with callosal agenesis, infantile spasms, chorioretinal
      lacunae, optic disc colobomas and cortical heterotopias were diagnosed with
      Aicardi syndrome. A choroid plexus papilloma was found in one patient, and
      choroid plexus cysts were found in the other. Choroid plexus lesions are common
      findings in the Aicardi syndrome and are discussed in this paper.

PMID- 9520083
TI  - Chronic childhood hydrocephalus associated with cavernous angioma compressing the
      superior sagittal sinus.
AB  - We report an autopsy case of a boy who, following drowning at the age of 15
      years, was found to have severe occult hydrocephalus and a cavernous angioma
      compressing the lumen of the superior sagittal sinus. We speculate that the cause
      of hydrocephalus was increased intrasinus pressure with impaired drainage of
      cerebrospinal fluid.

PMID- 9520084
TI  - Choroid plexus papilloma producing symptoms by secretion of cerebrospinal fluid.
AB  - A choroid plexus papilloma of the lateral ventricle presenting in early infancy
      and producing symptoms purely by secretion of cerebrospinal fluid with formation
      of a large cyst is presented. Initial conservative management by cyst-peritoneal
      shunt was followed by late recurrence of symptoms due to reformation of the cyst
      when the shunt blocked. Excision of the tumour afforded definitive relief.

PMID- 9520086
TI  - Expression of pancreatitis-associated protein (PAP) mRNA in gastrointestinal
      cancers.
AB  - CONCLUSION: Pancreatitis-associated protein (PAP) mRNA is expressed in some cases
      of gastric and colorectal cancers resulting from an ectopic expression in
      dedifferentiated cancer cells. BACKGROUND: The PAP gene is identical to the
      hepatoma-intestine-pancreas (HIP) gene, which is expressed in hepatoma.
      Expression in cancer might be another characteristic of PAP. METHODS: Fresh
      surgical specimens of 100 gastrointestinal cancers, 14 benign digestive diseases,
      and six normal organs were studied with nonisotopic in situ hybridization (ISH)
      using biotin-labeled cDNA probe. RESULTS: PAP mRNA was detected in 10% (6/60) of
      gastric cancers, 21.4% (6/28) of colorectal cancers, 20.0% (1/5) of pancreatic
      cancers and 0% of biliary tract (three), esophageal (one), and hepatocellular
      cancers (three). Reverse transcription-polymerase chain reaction (RT-PCR)
      detected PAP mRNA in these ISH-positive cases. PAP mRNA was not detected in
      noncancerous portions, benign disease tissues, or normal organs except for the
      small intestine. There was no relationship between PAP mRNA expression and any
      clinicopathological factors.

PMID- 9520085
TI  - Localization of galectin-3 in normal and diseased pancreatic tissue.
AB  - CONCLUSION: Galectin-3 is expressed in both human and hamster pancreatic tumors
      and tumor cell lines and this expression is increased over normal. BACKGROUND:
      Galectin-3 is overexpressed in many gastrointestinal tumors. This study examined
      the expression of galectin-3 in human and hamster pancreatic tumors to determine
      if galectin-3 could be used as a marker for pancreatic cancer. METHODS: Membranes
      were prepared from human and hamster pancreatic tumor cell lines. Galectin-3 was
      visualized by immunoblot analysis of separated membrane proteins using the
      monoclonal antibody (MAb) M3/38. Paraffin-embedded sections from normal,
      pancreatitis, and cancerous human pancreatic tissue and normal, N-nitrosobis(2
      oxopropyl)amine (BOP)-treated hyperplastic, and cancerous hamster pancreatic
      tissues were processed immunohistochemically for galectin-3 using the MAb M3/38.
      RESULTS: Galectin-3 was heavily expressed in cytoplasmic and nuclear regions of
      50% of normal human pancreatic tissue. Expression of galectin-3 in ductal cells
      in chronic pancreatitis and cancerous pancreatic tissue was increased over normal
      and was more uniform (>95% cells/duct stained). Normal hamster pancreatic ducts
      showed weak or no expression of galectin-3. Hyperplastic pancreatic ductal cells
      from BOP-treated hamsters heavily expressed galectin-3 (60-95% cells/duct
      stained). Galectin-3 expression in ductal cells in cancerous pancreatic lesions
      was increased to >95%. Galectin-3 was also detected in the pancreatic nerves in
      all human tissue specimens tested.

PMID- 9520087
TI  - Determination of fecal fat concentration by near infrared spectrometry for the
      screening of pancreatic steatorrhea.
AB  - CONCLUSIONS: Near infrared reflectance analysis (NIRA) is a useful test for
      diagnosing fat malabsorption. Three-day stool collection and determination of
      fecal fat output are recommended. The measurement of fat concentration on spot
      samples may be of some use only in screening malabsorption of pancreatic origin;
      moreover, it does not discriminate between steatorrhea resulting from pancreatic
      insufficiency and that caused by gastrointestinal disorders. BACKGROUND: NIRA has
      been proposed as an accurate method for the determination of fecal fat excretion.
      The aim of this study was to ascertain whether utilization of this technique to
      measure fat concentration in spot samples of feces is useful in screening for
      malabsorption. METHODS: Twenty-five patients with chronic pancreatic disease and
      95 with other digestive disorders were studied. In all patients, fecal fat assay
      with NIRA was performed on three different samples from each daily stool
      collection for 3 d. In 14 patients with pancreatic disease and 21 with
      gastrointestinal disorders, a colorimetric assay for fecal fat was performed for
      comparison. RESULTS: When mean 3-d or daily fat fecal output were considered, a
      strict linear relationship was found between NIRA and the colorimetric method (r
      = 0.97 and 0.94, respectively). Using fat concentration, the two tests correlated
      less well (r= 0.74). Fat concentration was significantly higher in pancreatic
      than in nonpancreatic steatorrhea, even though values overlapped widely, and thus
      discrimination was not possible. The diagnostic efficiency of fat concentration
      for pancreatic and nonpancreatic steatorrhea was 72 and 61%, respectively.

PMID- 9520088
TI  - An ultrastructural study to investigate the effect of allopurinol on cerulein
      induced damage to pancreatic acinar cells in rat.
AB  - CONCLUSION: Subcellular organelles and membranes were the structures most
      protected by allopurinol, indirectly demonstrating their role of main and early
      target of oxygen-derived free radicals in the pathogenesis of acute pancreatitis.
      BACKGROUND: The present work evaluates the ultrastructural changes during
      cerulein-induced acute pancreatitis in rat, with and without treatment with
      allopurinol. METHODS AND RESULTS: Supramaximal doses of cerulein, injected
      intraperitoneally (50 microg/kg) twice, at 1-h interval, caused severe
      subcellular alterations, including zymogen distribution, pathological vacuoles,
      and damage to organelles and membranes. Cotreatment (40 mg/kg ip twice with 1-h
      interval; n = 10 rats) and, most of all, pretreatment (40 mg/kg ip allopurinol, 1
      h; 20 mg/kg ip allopurinol + 50 microg/kg ip cerulein, 30 min; 40 mng/kg ip
      allopurinol, 30 min; 50 microg/kg ip cerulein; n = 10 rats) with allopurinol
      showed significant morphological improvement.

PMID- 9520089
TI  - Pancreatic bicarbonate response to intraduodenal tryptophan in dogs: role of
      muscarinic M1-receptors and cholecystokinin.
AB  - CONCLUSIONS: In dogs, 1. Activation of cholecystokinin-receptors is needed for an
      adequate pancreatic bicarbonate response to secretin; 2. Cholinergic nerve fibers
      ending on M1-receptors are probably of little or no importance for the
      bicarbonate response to secretin in the given dose; 3. The bicarbonate response
      to tryptophan, given with a secretin background, is controlled by cholinergic M1
      fibers and by cholecystokinin; 4. M1-fibers mainly mediate the bicarbonate
      response to low loads of tryptophan, whereas cholecystokinin controls the
      response to low and high loads of tryptophan; and 5. Both mediators interact in a
      synergistic manner. METHODS: In six conscious dogs with chronic gastric and
      duodenal fistulas, we compared the action of the M1-receptor antagonist
      telenzepine (20.25-81.0 nmol/kg/h), the cholecystokinin-receptor antagonist L
      364,718 (0.025-0.1 mg/kg/h), and combinations of both on the pancreatic
      bicarbonate response to graded loads of intraduodenal tryptophan (0.37-10.0
      mmol/h), given against a background of secretin (20.5 pmol/kg/h). RESULTS:
      Secretin significantly (p < 0.05) stimulated the pancreatic bicarbonate output
      above basal levels. All doses of L-374,718, but not telenzepine, significantly
      decreased the bicarbonate response to secretin by up to 64%. Additional
      administration of telenzepine together with L-364,718 had no further inhibitory
      effect on the secretin-stimulated bicarbonate output as compared to L-364,718
      given alone. All loads of tryptophan significantly increased the bicarbonate
      output over that seen with secretin alone (= incremental bicarbonate response to
      tryptophan). Telenzepine significantly decreased the incremental bicarbonate
      response to the two lower loads (0.37-1.1 mmol/h) of tryptophan (by 82-124%); L
      364,718 decreased the incremental bicarbonate response to all loads of tryptophan
      (by 50-118%). The incremental bicarbonate output, as well as the 180-min
      integrated bicarbonate response to all loads of tryptophan, were abolished by all
      combinations of both antagonists.

PMID- 9520090
TI  - Establishment and characterization of a new hamster pancreatic cancer cell line:
      the biological activity and the binding characteristics of EGF or TGF-alpha.
AB  - CONCLUSIONS: This new animal cell line may be a useful model to study the effect
      of growth factors on malignant cell proliferation and differentiation in both in
      vivo and in vitro systems. METHODS: We established a new pancreatic cancer cell
      line from pancreatic cancer in the hamster (HPC) induced by N-nitrosobis(2
      oxopropyl)amine (BOP) and characterized its morphological, pathological, and
      biological patterns. RESULTS: Cells grew rapidly, with a doubling time of 22.5 h.
      Chromosome number ranged from 33 to 144, and flow cytometric analysis showed two
      peaks of DNA distribution as a proliferative pattern. Ultrastructural analyses
      using transmission and scanning electron microscopy of HPC cells revealed
      desmosomes and loose interdigitation, with pseudopods and microvilli on the cell
      surface. The overexpression of epidermal growth factor (EGF) receptors on HPC
      cells was shown by immunohistochemistry. Binding characteristics and biological
      activity of EGF and type alpha transforming growth factor (TGF-alpha) were
      studied. TGF-alpha stimulated DNA synthesis in a dose-dependent manner, whereas
      EGF was without effect. Scatchard analysis of 125I-EGF binding data at pH 7.4
      indicated the presence of two orders of binding sites, where that of 125I-TGF
      alpha showed only a single order. Regarding the effect of pH on 125I-EGF or 125I
      TGF-alpha dissociation, one-half maximal dissociation of 125I-EGF or 125I-TGF
      alpha occurred at pH 6.0 or 6.5, respectively. Characteristics of the EGF
      receptor are similar to those of cultured human pancreatic cancer cells.

PMID- 9520091
TI  - Establishment and characterization of a new transplantable pancreatic cancer
      xenograft (PZX-5) in immunosuppressed mice.
AB  - CONCLUSION: A new, stable, transplantable human pancreatic cancer xenograft (PZX
      5) model has been established in CBA immunosuppressed mice. BACKGROUND: Numerous
      human pancreatic carcinomas have been successfully transplanted into athymic nude
      mice. However, artificially immunosuppressed animals have rarely been used as
      recipients. Because this model system proved to be reliable for hosting many
      human malignancies at our institute, successive xenotransplantations of a ductal
      adenocarcinoma have been carried out. METHOD: Immunosuppression of CBA/CA mice
      was achieved by thymectomy, whole-body irradiation and bone-marrow
      reconstruction. Tumor fragments were subcutaneously implanted from a
      well/moderately differentiated ductal pancreatic adenocarcinoma and serially
      transplanted for more than 20 mo. The xenografted tumors were characterized using
      morphological, immunohistochemical, biochemical, and flow cytometric methods.
      RESULTS: During the serial transplantations, the neoplasm maintained its original
      morphological-pathobiological characteristics. It produced a large amount of
      mucin and expressed carcinoembryonic antigen (CEA). Neither the mitotic activity
      nor the degree of differentiation was altered, and CEA was permanently detected.
      Flow cytometric DNA analysis revealed an aneuploid pattern (DNA index 1.45+/
      0.03), which has remained within the same range during xenograftings. The
      doubling time in an in vitro system proved to be 18 h. The human character has
      been well preserved even 9 mo posttransplantation, as was evidenced by LDH
      isoenzyme electrophoresis. The results indicate that the thymectomized--whole
      body irradiated--bone-marrow reconstructed immunosuppressed mice are also
      appropriate hosts for pancreatic cancer xenografts.

PMID- 9520093
TI  - Sclerosing cholangitis: a rare etiology for acute pancreatitis.
AB  - Primary sclerosing cholangitis as the cause of acute pancreatitis is a rare
      phenomenon with only one previous case having been found by ourselves in the
      English literature. Over a period of 2 yr, two patients with acute pancreatitis
      secondary to primary sclerosing cholangitis were seen in this unit. The first
      patient is currently being treated with ursodeoxycholic acid and repeat
      endoscopic sphincterotomies, whereas the second required liver transplantation.

PMID- 9520092
TI  - Effects of high-lipase pancreatin on fecal fat, neutral sterol, bile acid, and
      short-chain fatty acid excretion in patients with pancreatic insufficiency
      resulting from chronic pancreatitis.
AB  - CONCLUSIONS: Steatorrhea was almost completely stopped and malabsorption of
      neutral sterols and short-chain fatty acids was reduced by treatment of high
      lipase pancreatin in Japanese patients with pancreatic insufficiency whose
      dietary fat consumption is low. METHODS: Fifteen patients with chronic
      pancreatitis complicated by steatorrhea who consumed an average of 48 g of
      dietary fats a day were selected as subjects and given 3 g of high-lipase
      pancreatin (lipase, 379,800 USP U/g), at each meal (total daily dose is 9 g) for
      a mean duration of 28.5 d. Fecal output and fecal fat neutral sterol, bile acid,
      and short-chain fatty acid excretion were determined before and after the course
      of pancreatin therapy. RESULTS: Pancreatin administration resulted in significant
      reductions (P < 0.01) in fecal output (from 243.2 to 149.1 g), excretion of fecal
      fat, (from 12.3 to 3.9 g), animal sterols (from 816.3 to 604.6 mg), and short
      chain fatty acids (from 52.6 to 18.5 mM). In contrast, no marked changes were
      recorded in fecal excretion of beta-sitosterol (a plant sterol), bile acids, or
      the hydroxy fatty acid fraction. Fecal fat and short-chain fatty-acid excretion
      showed strong correlations with fecal output.

PMID- 9520094
TI  - Pancreatic mucin-producing tumor arising in the embryologically dorsal component
      of the head.

PMID- 9520095
TI  - Zurich workshop on alcoholic chronic pancreatitis.

PMID- 9520096
TI  - Immunocytochemical characterization of quisqualic acid- and N-methyl-D-aspartate
      induced excitotoxicity in the retina of chicks.
AB  - A single, large dose of N-methyl-D-aspartate (NMDA) or quisqualic acid (QA)
      injected into the chick eye has been shown previously to destroy many retinal
      amacrine cells and to induce excessive ocular growth accompanied by myopia. The
      purpose of this study was to identify distinct populations of retinal cells,
      particularly those believed to be involved in regulating ocular growth, that are
      sensitive to NMDA or QA. Two pmol of NMDA or 0.2 micromol of QA were injected
      unilaterally into eyes of 7-day-old chicks, and retinas were prepared for
      observation 1, 3, or 7 days later. Retinal neurons were identified by using
      immunocytochemistry, and cells containing fragmented DNA were identified by 3'
      nick-end labelling in frozen sections. NMDA and QA destroyed many amacrine cells,
      including those immunoreactive for vasoactive intestinal polypeptide, Met
      enkephalin, and choline acetyltransferase, but they had little effect upon
      tyrosine hydroxylase-immunoreactive cells. Other cells affected by both QA and
      NMDA included those immunoreactive for glutamic acid decarboxylase, gamma
      aminobutyric acid, parvalbumin, serotonin, and aminohydroxy methylisoxazole
      propionic acid (AMPA) receptor subunits GluR1 and GluR2/3. Cells largely
      unaffected by QA or NMDA included bipolar cells immunoreactive for protein kinase
      C (alpha and beta isoforms) and amacrine cells immunoreactive for glucagon. DNA
      fragmentation was detected maximally in many amacrine cells and in some bipolar
      cells 1 day after exposure to QA or NMDA. We propose that excitotoxicity caused
      by QA and NMDA induces apoptosis in specific populations of amacrine cells and
      that these actions are responsible for the ocular growth-specific effects of QA
      and NMDA reported elsewhere.

PMID- 9520097
TI  - Central projections of nerves innervating the rabbit maxillary sinus localized
      using wheat germ agglutinin-horseradish peroxidase or choleragenoid-horseradish
      peroxidase.
AB  - Central projections of nerves innervating the rabbit maxillary sinus were
      localized by using wheat germ agglutinin-horseradish peroxidase (WGA-HRP) or
      choleragenoid-horseradish peroxidase (B-HRP). Tracer was placed into the left
      maxillary sinus; rabbits were killed 3 or 5 days later, and histochemical
      localization of transported WGA-HRP or B-HRP was performed. Labeled cell bodies
      (437-545/animal) were seen in the ipsilateral trigeminal ganglion. Very few
      labeled cell bodies (zero to three/animal) were observed in the contralateral
      ganglion. The area of cell bodies labeled by WGA-HRP appeared similar to the area
      of cell bodies labeled by B-HRP. Transganglionic projections from either tracer
      were localized to lamina II of the ipsilateral subnucleus caudalis. In addition,
      WGA-HRP labeling was occasionally observed in lamina I. No labeling was present
      in other areas of the brainstem. In contrast to the above results, other studies
      have demonstrated that B-HRP produces terminal-like labeling in deeper layers of
      the gray matter. We injected B-HRP into the infraorbital nerve and sciatic nerve,
      which are known to contain projections to deep layers of the gray matter.
      Labeling was observed in the deep layers of the medullary or spinal dorsal horn 5
      days later, suggesting that nerves innervating the sinus only project to
      superficial laminae. These results suggest that neurons in superficial laminae of
      the subnucleus caudalis may be important for the reflex initiation of the
      increased glandular secretions in the maxillary sinus during sinusitis.

PMID- 9520098
TI  - FMRFamide-related peptides, partial serotonin depletion, and osmoregulation in
      Helisoma duryi (Mollusca: Pulmonata).
AB  - Serotonergic neurons were studied by specific histological methods, and neurons
      containing Phe-Met-Arg-Phe-NH2 (FMRFamide)-related heptapeptides were identified
      with an antiserum specific for these substances in the central nervous system of
      the freshwater snail Helisoma duryi. Serotonergic neurons and their axons are
      present in all of the ganglia (paired buccal, cerebral, pedal, pleural, parietal,
      and single visceral) and major nerves of the central nervous system. Large
      neurons containing FMRFamide-related peptide immunoreactivity are located in the
      left parietal and visceral ganglia, whereas a few small neurons are located in
      the cerebral and pedal ganglia. Both serotonergic and FMRFamide-related peptide
      immunoreactive dendrites and varicosities were observed in the kidney. A second
      antiserum with high affinity for FMRFamide-related heptapeptides was used to
      measure the levels of the immunoreactive material in various tissues, and such
      material was found in every tissue analyzed. When snails were exposed to a medium
      isosmotic to their hemolymph, the levels of immunoreactive FMRFamide-related
      peptides increased in the hemolymph, central nervous system, mantle, and kidney.
      Injection of dihydroxytryptamine, which is known to deplete serotonin content in
      the snail, also reduced the levels of FMRFamide-related-immunoreactive material
      in the above tissues. Therefore, serotonin may influence the levels of FMRFamide
      related peptides in tissues by regulating the rate of their synthesis, axonal
      transport, or release. Both serotonin and FMRFamide-related peptides could be
      involved in osmoregulation.

PMID- 9520099
TI  - Spatiotemporal appearance of developing LHRH neurons in the rat brain.
AB  - To obtain insight into the development of the heterogeneous intracerebral
      populations of luteinizing hormone-releasing hormone (LHRH) neurons, their
      spatiotemporal appearance was examined at different stages in normal rat embryos,
      in nasal epithelial explants in vitro, and in intrauterine nasal-operated
      embryos. Following the appearance of nerve cell adhesion molecule in the nasal
      placode at embryonic day (E) 12.5, LHRH neurons, generated in the nasal placode
      at E13.5, penetrated the forebrain vesicle (FV) by E14.5-15.5. After E16.5, as
      the FV elongated to form the olfactory bulb, the migrating neurons traversed
      posteriorly through the interhemispheric space to penetrate the septopreoptic (S
      P) area. By E18.5, LHRH neurons were detected in the preoptic-diagonal band (P-D)
      area as well as in the S-P region, along with some scattered extrahypothalamic
      LHRH neurons. To determine the source of these neurons, we separately cultured
      dissected parts of E12.5 nasal pit epithelium. Neuronal generation was
      predominantly from the medial wall epithelium (NAP), but some LHRH neurons
      originated in the roof epithelium. Cocultures of the NAP (E12.5) with the FV,
      median eminence-arcuate complex, Rathke's pouch, mesencephalon, or medulla
      oblongata from E14.5 embryos revealed the ability of LHRH cells to penetrate all
      of these tissues. Uni- or bilateral nasal destruction was conducted at E16.5 or
      E15.5, respectively, and examined at E18.5 and E21.5. In the operated embryos,
      most LHRH neurons were present in the P-D system and some in the S-P area. This
      finding suggests that the neurons generated before E15.5 are primarily
      predisposed to form the P-D system, whereas those derived afterward form the S-P
      system.

PMID- 9520100
TI  - Localization of gap junctions and tracer coupling in retinal Muller cells.
AB  - Physiological studies have demonstrated the existence of direct intercellular
      communication, presumably mediated by gap junctions, both between neurons and
      between glial cells in the vertebrate retina. We localized gap junctions in the
      retinas of rat, goldfish, and mudpuppy by using antisera directed against
      proteins that make up the connexon channels in two tissues from which connexins
      have been isolated: liver (connexin 32; CX32) and heart (connexin 43; CX43).
      Although the antiserum against CX32 stained liver gap junctions, it did not
      reveal any staining in rat or goldfish retina. The antiserum against CX43 stained
      gap junctions associated with the intercalated disk in rat heart and also stained
      gap junctions between pigment epithelium cells in rat, goldfish, and mudpuppy
      retina. Anti-CX43 also stained gap junctions between Muller cells in goldfish and
      mudpuppy retina but not in rat retina. Intracellular injections of the tracer
      Neurobiotin into Muller cells in the mudpuppy retina revealed that these glial
      cells are extensively tracer coupled. Staining with the tracer formed a syncytium
      of thin processes surrounding every neuron from the outer limiting membrane to
      the inner limiting membrane. Confocal microscopy demonstrated that the Muller
      cells were in close apposition with one another at every level of the retina.
      However, CX43 immunoreactivity was heaviest at the outer limiting membrane, where
      the apical processes of Muller cells are located. Some anti-CX43 staining was
      observed at the level of the outer nuclear layer and the inner plexiform layer
      but not in the ganglion cell layer or at the Muller cell end feet forming the
      inner limiting membrane.

PMID- 9520101
TI  - Three-dimensional organization of cell adhesion junctions at synapses and
      dendritic spines in area CA1 of the rat hippocampus.
AB  - Recent work has emphasized the role of adhesion molecules in synaptic plasticity,
      including long-term potentiation in the hippocampus. Such adhesion molecules are
      concentrated in junctions that are characterized by dense thickenings on both
      sides of the junction and are called puncta adhaerentia (PA). Reconstruction from
      serial electron microscopy was used to determine the location and size of PA in
      the stratum radiatum of hippocampal area CA1, where many of the previous
      functional studies have been performed. PAs were found at the edges of synapses
      on 33% of dendritic spines. The areas occupied by PA were variable across
      different types of synapses, occupying 0.010+/-0.005 microm2 at macular synapses
      and 0.034+/-0.031 microm2 at perforated synapses. Another zone, called a vesicle
      free transition zone (VFTZ), was identified. Like the PA, this zone also had no
      presynaptic vesicles and was located at the edges of synapses; however, unlike
      the PA, the presynaptic thickening was less than the postsynaptic thickening.
      Together, 45% of spine synapses had PA and/or VFTZ occupying 23+/-11% of the
      total junctional area between axons and spines. PA also occurred at nonsynaptic
      sites involving neuronal as well as glial elements. Most (64%) of these PAs
      occurred between nonsynaptic portions of dendritic spines and neighboring
      astrocytic processes. Smooth endoplasmic reticulum was often apposed to one or
      both sides of the synaptic and the nonsynaptic PA. These findings provide further
      data as a structural basis for understanding the roles of cell adhesion junctions
      in hippocampal synaptic function and plasticity.

PMID- 9520102
TI  - Distribution of 5-hydroxytryptamine-immunoreactive boutons on alpha-motoneurons
      in the lumbar spinal cord of adult cats.
AB  - Recent studies have shown that at least some of the functional effects of
      serotonin (5-HT) on motoneuron excitability are direct and are mediated via
      postsynaptic 5-HT receptors on motoneurons. To determine the spatial distribution
      of direct inputs from the serotonin system on the proximal and distal dendrites
      of individual motoneurons, we examined identified motoneurons in vivo with a
      combination of immunohistochemical localization of 5-HT-immunoreactive boutons
      and intracellular staining with horseradish peroxidase. Seventeen intracellularly
      stained motoneurons from 12 adult cats were analyzed with light microscopy.
      Quantitative analysis of 5-HT boutons apposed to dendrites of five representative
      motoneurons that were entirely reconstructed in three dimensions (each from the
      lumbosacral spinal cord of a different animal) revealed a total of 7,848 contacts
      (1,570+/-487 contacts/postsynaptic neuron; mean +/- SD) over the dendrites of
      these cells. Analysis of contacts on the soma of two of these cells, and on the
      somas of an additional 12 intracellularly stained motoneurons, revealed a wide
      range of somatic contacts (11-211 contacts/cell) on motoneuron cell bodies, with
      an average of 52 contacts/cell. These results indicate that the vast majority of
      5-HT-immunoreactive boutons are apposed to dendritic branches rather than to the
      somatic surface of motoneurons. The spatial distribution of contacts essentially
      matched the distribution of surface membrane area of the postsynaptic neuron,
      resulting in a relatively uniform density of contacts (<1/100 microm2) on
      proximal and distal dendrites. Consequently, the frequency of contacts was higher
      on the proximal dendritic compartments where available membrane area is greater.
      There was no preferential distribution of contacts to particular dendrites.
      Light/electron microscopic correlations were performed on 21 boutons that
      contacted dendrites (n = 7) of three motoneurons from different animals. At the
      electron microscope level, most appositions (18/21; 85.7%) selected by our light
      microscopic criteria were confirmed as direct contacts when the 5-HT boutons were
      examined through serial sections. Synaptic junctions, generally small and
      symmetric, were positively identified in only a subset of these cases (n = 6;
      28.6%), in part due to the obscuring effects of the peroxidase histochemical
      precipitate present in both pre- and postsynaptic profiles. A few 5-HT boutons
      (3/21; 14.3%) selected as contacts by our light microscopic criteria were in fact
      separated from the adjacent labeled dendrites; in two of these three cases, the
      separation was due to intrusion of very thin glial lamellae (<0.3 microm in cross
      section). These results indicate that the bulbospinal serotonergic system(s)
      provide a significant, direct synaptic input to spinal motoneurons that innervate
      hindlimb muscles. The nature of the modulatory actions exerted by such widespread
      synaptic inputs will affect all regions of the somatodendritic membrane and will
      ultimately depend on the nature of the 5-HT receptors present over different
      parts of the postsynaptic neuron's dendritic tree.

PMID- 9520103
TI  - Augmentation of serotonin in the developing superior colliculus alters the normal
      development of the uncrossed retinotectal projection.
AB  - A previous study from this laboratory showed that sprouting of serotoninergic
      axons in the hamster's superior colliculus (SC) induced by a single subcutaneous
      injection of 5,7-dihydroxytryptamine (5,7-DHT) at birth (postnatal day 0; P-0)
      resulted in an abnormal terminal distribution of the uncrossed retinotectal
      projection. The present study provided further evidence to support the role of
      increased 5-HT levels within the SC in this phenomenon. Slow-release polymer
      (ELVAX) chips impregnated with serotonin (5-HT) were placed over the SC on either
      P-1 or P-3, and retinotectal projections were assessed via anterograde transport
      of horseradish peroxidase when animals reached P > 18. Analysis of ELVAX chips
      indicated that they released 5-HT in amounts of > or = 1 pmole/hour for at least
      12 days. Assessment of the SC of treated hamsters indicated significantly
      elevated 5-HT concentrations as late as P-12, but not on P-16. Implantation of 5
      HT chips, but not control chips, resulted in abnormalities in the uncrossed
      retinotectal projection similar to those observed in the 5,7-DHT-treated animals.
      The patches that normally develop in the rostral part of the stratum opticum were
      not present, and uncrossed axons were distributed densely in this layer and in
      the lower portion of the stratum griseum superficiale throughout the rostrocaudal
      and mediolateral extents of the SC. Quantitative analysis of these changes
      indicated significant differences between the organization of the uncrossed
      retinotectal projections of 5-HT-treated animals vs. either blank-implant treated
      or completely untreated animals but not between 5-HT-treated hamsters and animals
      that received neonatal 5,7-DHT injections. All of these results support the
      conclusion that increased SC concentrations of 5-HT altered retinotectal
      development.

PMID- 9520104
TI  - Expression of the somatostatin subtype 2A receptor in the rabbit retina.
AB  - In the retina, somatostatin influences neuronal activity likely by acting at one
      or more somatostatin subtype (sst) receptors. Somatostatin and somatostatin
      binding sites are distributed predominantly to the inner retina. The present
      study has investigated the cellular expression of one of the sst receptors, the
      sst2A receptor isoform, in the rabbit retina. These studies have used a new
      polyclonal antibody directed to the predicted C-terminus of mouse sst2A(361-369)
      receptor. Antibody specificity was tested by preadsorption of the primary
      antibody with a peptide corresponding to sst2A(361-369). sst2A Receptor
      immunoreactivity was localized mainly to the plasma membrane of rod bipolar cells
      and to sparsely occurring, wide-field amacrine cells. Immunostaining in rod
      bipolar cells was strongest in the axon and axon terminals in lamina 5 of the
      inner plexiform layer (IPL) and was weakest in the cell body and dendrites.
      Double-labeling experiments using a monoclonal antibody against protein kinase C
      (PKC; alpha and beta), a rod bipolar cell-selective marker, showed complete
      colocalization. In horizontal sections of retina, immunostained bipolar cell
      bodies had a dense distribution, which is in agreement with the reported
      distribution of rod bipolar cell bodies. Immunoreactive amacrine cell bodies were
      located at the border of the inner nuclear layer and the IPL, and thin varicose
      processes ramified mainly in laminae 2 and 4 of the IPL. These observations
      indicate that somatostatin influences visual information processing in the retina
      1) by acting presynaptically on rod bipolar cell axon terminals and b) by
      influencing the activity of sparsely occurring amacrine cells.

PMID- 9520105
TI  - Axonal transport of neurotrophins by visceral afferent and efferent neurons of
      the vagus nerve of the rat.
AB  - The receptor-mediated axonal transport of [125I]-labeled neurotrophins by
      afferent and efferent neurons of the vagus nerve was determined to predict the
      responsiveness of these neurons to neurotrophins in vivo. [125I]-labeled
      neurotrophins were administered to the proximal stump of the transected cervical
      vagus nerve of adult rats. Vagal afferent neurons retrogradely transported
      [125I]neurotrophin-3 (NT-3), [125I]nerve growth factor (NGF), and
      [125I]neurotrophin-4 (NT-4) to perikarya in the ipsilateral nodose ganglion, and
      transganglionically transported [125I]NT-3, [125I]NGF, and [125I]NT-4 to the
      central terminal field, the nucleus tractus solitarius (NTS). Vagal afferent
      neurons showed minimal accumulation of [125I]brain-derived neurotrophic factor
      (BDNF). In contrast, efferent (parasympathetic and motor) neurons located in the
      dorsal motor nucleus of the vagus and nucleus ambiguus retrogradely transported
      [125I]BDNF, [125I]NT-3, and [125I]NT-4, but not [125I]NGF. The receptor
      specificity of neurotrophin transport was examined by applying [125I]-labeled
      neurotrophins with an excess of unlabeled neurotrophins. The retrograde transport
      of [125I]NT-3 to the nodose ganglion was reduced by NT-3 and by NGF, and the
      transport of [125I]NGF was reduced only by NGF, whereas the transport of [125I]NT
      4 was significantly reduced by each of the neurotrophins. The competition
      profiles for the transport of NT-3 and NGF are consistent with the presence of
      TrkA and TrkC and the absence of TrkB in the nodose ganglion, whereas the profile
      for NT-4 suggests a p75 receptor-mediated transport mechanism. The transport
      profiles of neurotrophins by efferent vagal neurons in the dorsal motor nucleus
      of the vagus and nucleus ambiguus are consistent with the presence of TrkB and
      TrkC, but not TrkA, in these nuclei. These observations describe the unique
      receptor-mediated axonal transport of neurotrophins in adult vagal afferent and
      efferent neurons and thus serve as a template to discern the role of specific
      neurotrophins in the functions of these visceral sensory and motor neurons in
      vivo.

PMID- 9520107
TI  - Differential expression of myosin heavy chain mRNA and protein isoforms in four
      functionally diverse rabbit skeletal muscles during pre- and postnatal
      development.
AB  - Myosin heavy chains (hcs) are the major determinant in the speed of contraction
      of skeletal muscle, and various isoforms are differentially expressed depending
      on the functional activity of the muscle. Using the rapid amplification of cDNA
      ends (3' RACE) method, we have characterised the 3' end of the embryonic,
      perinatal, type 1, 2a, 2x, and 2b myosin hc genes in rabbit skeletal muscle and
      used them as probes in RNase protection assays to quantitatively monitor their
      expression in different type of skeletal muscles just before and after birth. SDS
      PAGE was used to study the changes in the expression level of their respective
      protein and to determine the relative abundance of each myosin hc isoform in the
      muscles studied. The results show that for each anatomical muscle, the
      developmental changes in myosin hc gene expression at the mRNA level correlate
      strongly to those observed at the protein level. By studying their developmental
      expression in four functionally diverse skeletal muscles (semimembranosus
      proprius, diaphragm, tibialis anterior, and semimembranosus accessorius), it was
      shown that all muscles express the embryonic, perinatal, and type 1 isoform
      during prenatal development up to the E27 stage. In the diaphragm, low levels of
      the type 2a and 2x transcripts, which are adult fast isoforms, were also detected
      at the E27 stage. During the first week of postnatal growth the myosin hc
      transition leading to the expression of the adult isoforms is complex, and as
      many as five different myosin heavy chains are concurrently expressed in some
      muscles at around birth. As the animal matures, individual muscles become adapted
      to perform highly specialised functions, and this is reflected in the myosin hc
      composition within these muscles. Accordingly, the expression of the type 1
      isoform, and the sequence of appearance and the expression levels of the type 2
      isoforms, were exclusively dependent on the muscle type and largely reflect the
      functional activity of each muscle during the postnatal growth period.

PMID- 9520106
TI  - Transient molecular visualization of ocular dominance columns (ODCs) in normal
      adult marmosets despite the desegregated termination of the retino-geniculo
      cortical pathways.
AB  - The activity-dependent immediate early gene protein Krox-24, expressed in the
      neocortex at high basal levels, decreases rapidly upon neuronal deactivation
      (Chaudhuri et al. [1995] Vis. Neurosci. 12:35-50). In infant marmosets, as in
      most primates, the geniculo-cortical terminations segregate into eye-specific
      anatomical ocular dominance columns (ODCs), which disappear, however, during
      adolescence (Spatz [1989] Brain Res. 488:376-380), resulting in balanced inputs
      from the two eyes (Sengpiel et al. [1996] Vis. Neurosci. 13:145-160).
      Nevertheless, we found, in adult marmosets, 24 hours after monocular retinal
      activity blockade by tetrodotoxin, distinct alternating compartments of
      potentiated and depressed Krox-24-like immunoreactivity (Krox-IR) in layer IV of
      area 17. This pattern of Krox-IR disappeared at 10 days of retinal silencing, but
      was still present at this survival time in stains for cytochrome oxidase or NADPH
      diaphorase. After 20 days of retinal silencing, the pattern was not demonstrable
      with any of the three stains. We term these compartments physiological ODCs, in
      contrast to the anatomical ODCs of most primates. If the anatomical ODCs of
      infant marmosets disappear by collateral sprouting into the inappropriate ODCs,
      then the collateral geniculo-cortical synapses might differ slightly in their
      properties from the original ones. We silenced the sets of original and
      collateral synapses of the one ocularity. This apparently transiently initiated,
      at the synapses driven by the intact eye, two different complex processes leading
      to molecular potentiation at the original synapses and to molecular depression at
      the collateral synapses.

PMID- 9520108
TI  - Cell-cell adhesion in limb-formation, estimated from photographs of cell sorting
      experiments based on a spatial stochastic model.
AB  - We developed a new method to estimate the magnitude of differential cell-cell
      adhesion of two tissues based on the spatial patterns in cell-sorting
      experiments, and applied it to experimental data on progress-zone cells of avian
      limb bud at stages 20-26. The change in cell distribution in the experiment was
      recorded, and statistics qB/B for the degree of cell sorting was calculated from
      the photographs. Based on extensive computer simulations of spatial Markov
      processes on a 2-D lattice, we derived a formula for qB/B increasing with time.
      Using least square fitting, differential adhesion A and cell motility m are
      estimated from the time series data of qB/B obtained from the experiment. The
      estimated A was close to 0 (the spatial pattern remained random) if the mixed
      cells were from two tissues of the same stage. If the mixed cells were from
      different stages, and the estimated A was positive (cell sorting occurred).
      Estimated A increased with the difference in the stage number of the two tissues
      from which the cells were sampled. This result can be explained both by the stage
      specific change in adhesion molecules and by a linear increase (or decrease) in
      the amount of adhesion molecules on cell surface.

PMID- 9520109
TI  - VEGF enhances pulmonary vasculogenesis and disrupts lung morphogenesis in vivo.
AB  - Vascular endothelial growth factor (VEGF) was expressed in developing respiratory
      epithelial cells under control of the promoter from the human surfactant protein
      C (SP-C) gene. SP-C-VEGF transgenic mice did not survive after birth. When
      obtained by hysterectomy on embryonic day 15 (E15) or 17 (E17), abnormalities in
      the transgenic mice were confined to the lung and were correlated with the
      expression of transgene mRNA as revealed by in situ hybridization. On E15 and
      E17, marked abnormalities in lung morphogenesis were observed in transgenic mice.
      Lungs consisted of large dilated tubules with increased peritubular vascularity.
      The mRNA levels of the VEGF receptor, Flk-1, and the endothelial cell specific
      receptor tyrosine kinase, Tie-1, were increased in lung mesenchyme of the
      transgenic mice. The numbers of acinar tubules and the abundance of mesenchyme
      were decreased. Endogenous VEGF mRNA was expressed in the respiratory epithelial
      cells of the developing lungs, and the levels of VEGF mRNA were increased in the
      SP-C-VEGF transgenic mice. Although the normal pattern of immunostaining for SP-C
      and Clara cell secretory protein (CCSP) indicated that epithelial cell
      differentiation was relatively unaltered by the transgene, electron microscopic
      analysis revealed a lack of alveolar Type I cell differentiation at E18.
      Expression of VEGF in the developing respiratory epithelium of transgenic mice
      increased growth of the pulmonary blood vessels, disrupted branching
      morphogenesis of the lung and inhibited Type I cell differentiation.

PMID- 9520110
TI  - Temporal and spatial regulation of gene expression mediated by the promoter for
      the human tissue inhibitor of metalloproteinases-3 (TIMP-3)-encoding gene.
AB  - A complex interplay between enzymes involved in extracellular matrix formation
      and their inhibitors is thought to control organogenesis during mammalian
      development. Disturbance of this balance may result in a wide range of diseases,
      including macular degeneration, arthritis, and tumor metastases. In order to
      define elements which may be involved in regulating human tissue inhibitor of
      metalloproteinase 3 (TIMP3) expression, we isolated and sequenced a clone
      containing 1315 bp of the 5'-upstream region of the human TIMP-3-encoding gene. A
      1.2 kb fragment of this clone, which contains multiple motifs which are binding
      sites for known transcription factors, was used to drive expression of the lacZ
      reporter gene in multiple lines of transgenic mice. TIMP3 promoter activity,
      detected through beta-galactosidase histochemical assay, was observed at high
      levels in selected tissues, the identity of which varied according to
      developmental stage. TIMP3 promoter activity was detected at embryonic and early
      postnatal stages in tissues undergoing extensive remodeling, such as developing
      somites, bones and joints, choroid plexus, webs between the digits, and the
      spongiotrophoblastic portion of the placenta. In adulthood, TIMP3 promoter
      activity was restricted to a few tissues which exhibit high metabolic activity or
      rapid turnover. These include the retinal pigment epithelium (RPE), cells of the
      kidney cortex, hair follicles, gingiva, ovarian follicles, and testis. The
      results suggest that TIMP3 expression plays an active role in developmental
      patterning and in the maintenance of specific differentiated tissues.

PMID- 9520111
TI  - Regulated expression of cadherin-6 and cadherin-11 in the glandular epithelial
      and stromal cells of the human endometrium.
AB  - The cadherins are key morphoregulators. A switch in the cadherin subtype(s)
      expressed by a population of cells has been associated with the differentiation
      and formation of tissues during embryonic development. To date, the role(s) of
      the cadherins in the highly regulated remodeling processes which occur in the
      human endometrium in preparation for the implanting embryo remain poorly
      characterized. Here we report that two atypical cadherins, known as cadherin-6
      and cadherin-11, are spatiotemporally expressed in the human endometrium during
      the menstrual cycle. Cadherin-6 levels are high in both the glandular epithelium
      and stroma of the endometrium during the follicular phase and decline as the
      cycle enters the luteal phase. The down-regulation of cadherin-6 in the glandular
      epithelium during the luteal phase does not effect the levels of cadherin-11 in
      this cell type. In contrast, the loss of cadherin-6 expression in endometrial
      stroma cells is concomitant with an increase in the levels of cadherin-11.
      Collectively, these observations suggest that multiple factors regulate the
      expression of these two endometrial cadherins. As a first step in identifying
      these factors, we examined the effects of progesterone on cadherin-6 and cadherin
      11 expression in isolated endometrial stromal cells. Progesterone was capable of
      differentially regulating the expression of these two stromal cell adhesion
      molecules. These findings lend further support to our hypothesis that steroids
      are key regulators of cadherin expression in mammalian tissues.

PMID- 9520112
TI  - Expression of type VI collagen in the developing mouse heart.
AB  - During development, the embryonic atrioventricular (AV) endocardial cushions
      undergo a morphogenic process to form mature valve leaflets and the membranous
      septa in the heart. Several extracellular matrix (ECM) proteins are expressed in
      the developing AV endocardial cushions, but it remains to be established if any
      specific ECM proteins are necessary for normal cushion morphogenesis. Abnormal
      development of the cardiac AV valves is a frequent cause of congenital heart
      defects, particularly in infants with trisomy 21 (Down syndrome). The genes
      encoding the alpha1 and alpha2 chains of type VI collagen are located on human
      chromosome 21 within the region thought to be critical for congenital heart
      defects in trisomy 21 infants. This suggests that the type VI collagen alpha1(VI)
      and alpha2(VI) chains may be important in normal AV valve morphogenesis. As a
      first step in understanding the role of type VI collagen in valve development,
      the authors examined the normal spatial and temporal expression patterns of mRNA
      and protein for type VI collagen in the embryonic mouse heart. Ribonuclease
      protection assay analysis demonstrates cardiac expression of the type VI collagen
      for alpha1(VI), alpha2(VI), and alpha3(VI) transcripts beginning at embryonic
      days 11-11.5 of mouse development. In situ hybridization studies demonstrate a
      coordinated pattern of cardiac expression within the AV valves for each type VI
      collagen chain from embryonic day 11.5 through the neonatal period.
      Immunohistochemical studies confirm a concentrated type VI collagen localization
      pattern in the endocardial cushions from the earliest stages of valve development
      through the neonatal period. These data indicate that type VI collagen is
      expressed in the developing AV canal in a pattern consistent with cushion tissue
      mesenchymal cell migration and proliferation, and suggest that type VI collagen
      plays a role in the morphogenesis of the developing cardiac AV endocardial
      cushions into the valve leaflets and membranous septa of the heart.

PMID- 9520113
TI  - Expression and function of FGFs-4, -8, and -9 suggest functional redundancy and
      repetitive use as epithelial signals during tooth morphogenesis.
AB  - To elucidate the roles of fibroblast growth factors (FGF) in the regulation of
      tooth morphogenesis we have analyzed the expression patterns of Fgf-4, -8, and -9
      in the developing mouse molar and incisor tooth germs from initiation to
      completion of morphogenesis by in situ hybridization analysis. The expression of
      these Fgfs was confined to dental epithelial cells at stages when epithelial
      mesenchymal signaling regulates critical steps of tooth morphogenesis. Fgf-8 and
      Fgf-9 mRNAs were present in the oral epithelium of the first branchial arch at
      E10 and 1 day later expression became more restricted to the area of presumptive
      dental epithelium and persisted there until the start of epithelial budding. Fgf
      8 mRNAs were not detected later in the developing tooth. Fgf-4 and Fgf-9
      expression was upregulated in the primary enamel knot, which is a putative
      signaling center regulating tooth shape. Subsequently, Fgf-4 and Fgf-9 were
      expressed in the secondary enamel knots at the sites of tooth cusps. Fgf-9
      expression spread from the primary enamel knot within the inner enamel epithelium
      where it remained until E18. In the continuously growing incisors Fgf-9
      expression persisted in the epithelium of the cervical loops. The effects of FGFs
      were analyzed on the expression of the homeobox-containing transcription factors
      Msx-1 and Msx-2, which are associated with tissue interactions and regulated by
      the dental epithelium. Locally applied FGF-4, -8, and -9 stimulated intensely the
      expression of Msx-1 but not Msx-2 in the isolated dental mesenchyme. We suggest
      that the three FGFs act as epithelial signals mediating inductive interactions
      between dental epithelium and mesenchyme during several successive stages of
      tooth formation. This data suggest roles for FGF-8 and FGF-9 during initiation of
      tooth development, and for FGF-4 and FGF-9 during regulation of tooth shape. FGF
      9 may also be involved in differentiation of odontoblasts. The coexpression of
      Fgfs with other signaling molecules including Shh and several Bmps and their
      partly similar effects suggest that the FGFs participate in the signaling
      networks during odontogenesis.

PMID- 9520114
TI  - Fetal development of the enteric nervous system of transgenic mice that
      overexpress the Hoxa-4 gene.
AB  - Megacolon occurs in neonatal and adult transgenic mice that overexpress the Hoxa
      4 gene. Abnormalities, which are restricted to the terminal colon of these mice,
      include a hypoganglionosis, abnormal enteric ganglia with a structure appropriate
      for extra-enteric peripheral nerve and not the enteric nervous system (ENS), and
      gaps in the longitudinal muscle occupied by ganglia. To investigate the
      developmental origin of these abnormalities, we analyzed the development of the
      pelvis and terminal colon in Hoxa-4 transgenic mice. Morphological abnormalities
      were detected as early as E13. These included an enlargement of the mucosa and
      the bowel wall, a thickening of the enteric mesenchyme, and the ectopic location
      of pelvic ganglion cells, which initially clustered on the dorsolateral wall of
      the hindgut. As the bowel enlarged, these ectopic cells become ventrolateral and,
      between days E17 and E18.5, appeared to become incorporated into the gut, leaving
      neuron-filled gaps in the longitudinal muscle layer. The ectopic ganglia retained
      extra-enteric characteristics, including the presence of capillaries, basal
      laminae, collagen fibers, and catecholaminergic neurons, even after their
      incorporation into the bowel. It is proposed that the abnormal and ectopic
      expression of the Hoxa-4 transgene in the colon causes signalling molecule(s) of
      the enteric mesenchyme to be overproduced and that the overabundance of these
      signals leads to mucosal enlargement and misdirection of migrating pelvic
      neuronal progenitors.

PMID- 9520115
TI  - Lp(a) lipoprotein level predicts survival and major coronary events in the
      Scandinavian Simvastatin Survival Study.
AB  - The Scandinavian Simvastatin Survival Study (4S) was a double-blind, randomized
      placebo-controlled multi-centre clinical trial of long-term Simvastatin therapy
      in patients with coronary heart disease who had total cholesterol levels between
      5.5 and 8.0 mmol/l, comprising 4444 patients, equally distributed to a
      Simvastatin and a placebo group. Patients achieved a significant 30% relative
      reduction in overall mortality with Simvastatin therapy through a 42% relative
      reduction in coronary heart disease mortality. Lp(a) lipoprotein levels in
      Scandinavian coronary heart disease patients were strikingly higher than in
      healthy controls. Numbers of deaths in the Simvastatin group differed
      significantly between quartiles of Lp(a) lipoprotein levels, the reduction in
      deaths being most pronounced in the second (next to lowest) quartile. Subjects
      with major coronary events had significantly higher Lp(a) lipoprotein levels than
      subjects without such events, in all groups. The relationship between Lp(a)
      lipoprotein level and total mortality as well as between Lp(a) lipoprotein level
      and major coronary events was significantly different from zero, in logistic
      regression analyses. The findings show that Lp(a) lipoprotein predicts major
      coronary events as well as death in secondary prevention with Simvastatin. This
      prospective study provides independent confirmation that a high Lp(a) lipoprotein
      level is a significant coronary heart disease risk factor.

PMID- 9520116
TI  - Lipoprotein(a) in plasma, arterial wall, and thrombus from patients with aortic
      aneurysm.
AB  - The plasma concentration of lipoprotein(a) [Lp(a)] is highly correlated with the
      incidence of cardiovascular and peripheral vascular disease. A positive
      physiological role for Lp(a) has not yet been clearly identified, although
      elevated plasma levels in pregnant women, long-distance runners, subjects given
      growth hormone, patients after cardiovascular surgery, and patients with cancer,
      diabetes, or renal disease suggest its involvement in tissue synthesis and
      repair. The hypothesis that Lp(a) is involved in repair/reinforcement of the
      aorta was tested in 38 patients undergoing surgery for aortic aneurysm. In 29
      patients 1 day before surgery, the mean plasma Lp(a) protein level was 10.7
      mg/dl. At about 1, 2, and 8 weeks after surgery, the level was 14.1, 15.1, and
      15.2 mg/dl, respectively. These levels are significantly higher than those of a
      comparable group of normal subjects (6.4 mg/dl; n = 274). Specimens of resected
      aortic aneurysm showed extensive medial degeneration, discontinuous elastic
      fibers, and deposition of mucopolysaccharides; these specimens were treated with
      a detergent-containing buffer to extract entrapped lipoproteins. The mean Lp(a)
      protein level in aortic wall extracts was 14.6 ng/mg tissue; these individual
      values were significantly associated with plasma Lp(a) levels before surgery (r2
      = 0.31, p = 0.0003). The mean Lp(a) protein level in aortic thrombus extracts was
      substantially higher at 69.6 ng/mg tissue; these individual levels also were
      significantly associated with plasma Lp(a) concentrations before surgery (r2 =
      0.68, p < 0.0001). The observations that: (i) plasma Lp(a) protein is about 1.7
      fold higher in patients with aortic aneurysms than in normal subjects; and (ii)
      that Lp(a) protein in the aneurysmic thrombus is about 4.8-fold higher than in
      the aortic wall suggest that this lipoprotein plays a significant and direct role
      in thrombus formation and in reinforcement of the aneurysmic aortic wall.

PMID- 9520117
TI  - Lp(a) lipoprotein is a major risk factor for cardiovascular disease: pathogenic
      mechanisms and clinical significance.
AB  - The results of two previous and two recent studies of middle-aged males and
      females are presented to exemplify the clinical importance of lipoprotein(a)
      (Lp(a)) as a risk factor for atherosclerosis and coronary heart disease. In these
      studies various conventional and recently suggested risk factors were included
      and different methods for Lp(a) quantification were used. Lp(a) was a significant
      risk factor in all four studies. In the recent prospective case-control study,
      Lp(a) and cholesterol were found to act synergistically and predict primary acute
      myocardial infarction in Swedish males. A cholesterol level above 6.5 mmol/l
      increased the risk of acute myocardial infarction if the Lp(a) level was above
      200 mg/l. The plasma apo A-I level was a protective factor. In the other recent
      case-control study, an Lp(a) level above 500 mg/l was a highly significant risk
      factor in Black and White US women with myocardial infarction or advanced
      coronary artery disease in addition to low density lipoprotein cholesterol levels
      above 130 mg/dl. A high apo A-I level was a protective factor. In these studies
      no other factors tested reached significance in multivariate logistic regression
      analysis. A hypothetical association between high Lp(a) levels and intracellular
      infection with Chlamydia pneumoniae is discussed. The results suggest that the
      Lp(a) level is useful in identifying high-risk individuals. Lowering low density
      lipoprotein cholesterol below 100 mg/dl (<2.6 mmol/l) seems to be most important
      in both males and females with high-risk Lp(a) levels.

PMID- 9520118
TI  - Epidemiology of Lp(a) lipoprotein: its role in atherosclerotic/thrombotic
      disease.

PMID- 9520119
TI  - High-degree sequence conservation in LPA kringle IV-type 2 exons and introns.
AB  - In the search for factors contributing to the regulation of the Lp(a) lipoprotein
      concentration, we have sequenced the kringle IV-type 2 encoding exons 1 and 2
      together with the flanking intron sequences of the LPA gene in individuals with
      different serum concentrations of Lp(a) lipoprotein. The high degree of sequence
      identity between the kringle IV-type 2 repeats made it possible to analyse all
      the 3-42 kringles simultaneously by polymerase chain reaction and direct DNA
      sequencing. The strategy used allowed us to determine approximately 700 bp from
      each kringle IV-type 2 repeat, resulting in a rapid screen of on average 28,000
      bp of the LPA gene from each individual. Comparing these bipartite kringle IV
      type 2 repeat sequences from 12 individuals with high and 11 individuals with low
      Lp(a) lipoprotein level revealed that: 1. no sequence polymorphism could be
      detected in the exons examined; 2. no sequence polymorphism could be detected in
      the consensus GT/AG splicing signals of exon/intron junctions; and 3. the
      proximal intron sequences seemed almost completely conserved in the 76-135 bp
      analysed. Only one position in the intron sequences exhibited the pattern of a
      G/A polymorphism. We observed no differences between the group with high and the
      group with low Lp(a) lipoprotein level. The very high conservation of intron
      sequences could support the hypothesis that the LPA gene evolved relatively
      recently. The contradictory finding of a corresponding sequence conservation
      between the human LPA and the plasminogen gene suggests that an evolutionary
      pressure has preserved these intron sequences over the last 40-90 million years.

PMID- 9520120
TI  - Reporter gene analysis of four DNaseI hypersensitive sites in the
      plasminogen/apolipoprotein(a) intergenic region.
AB  - We have previously described four DNaseI hypersensitive sites (DH 1 to DH4) in
      the 40-kb intergenic region between the plasminogen gene and the apo(a) gene.
      Here, we wanted to analyse whether any of these sites, located 4, 21, 28 and 34
      kb upstream of the apo(a) transcriptional start site, would act as an enhancer on
      a minimal apo(a) promoter. Starting from a cloned, highly expressed apo(a)
      allele, we obtained four fragments comprising the DHI to DH4 sites, respectively.
      These fragments were cloned in both orientations into a luciferase reporter gene
      plasmid comprising a minimal apo(a) promoter (-100 to +141 with respect to the
      transcriptional start site). Our results from transfection studies with the
      resulting series of reporter gene plasmids into liver (HepG2) and non-liver
      (HeLa) cells suggest that the four DH sites from the selected apo(a) allele do
      not provide a strong, liver-specific enhancer activity.

PMID- 9520121
TI  - Apolipoprotein(a) is a human vascular endothelial cell agonist: studies on the
      induction in endothelial cells of monocyte chemotactic factor activity.
AB  - Elevated levels of lipoprotein(a), Lp(a), are associated with premature
      atherosclerosis; however, the mechanisms of its atherogenicity are not known.
      Recruitment of monocytes to the blood vessel wall is an early event in
      atherogenesis. Since Lp(a) is associated with macrophages in the plaque, we have
      examined the effect of Lp(a) on inducing monocyte chemotactic activity (MCA) in
      vascular endothelial cells. We report that Lp(a) and apo(a) induced human
      umbilical vein (HUVEC) and coronary artery endothelial cells to secrete monocyte
      chemotactic activity as early as 30 min of incubation. In the absence of cells,
      Lp(a) had no direct monocyte chemotactic activity. Actinomycin D and
      cycloheximide inhibited the HUVEC response, indicating that protein and RNA
      synthesis were required. Endotoxin was shown not to be responsible for the
      induction of monocyte chemotactic activity. Granulocyte monocyte-colony
      stimulating factor antigen was not detected in the Lp(a)-conditioned medium, nor
      was monocyte chemoattractant protein-1 mRNA induced by Lp(a). These results
      suggest that Lp(a) may be involved in the recruitment of monocytes to the vessel
      wall, thus providing a novel mechanism for the participation of Lp(a) in the
      atherogenic process.

PMID- 9520122
TI  - Studies on effects of Lp(a) lipoprotein on gene expression in endothelial cells
      in vitro.
AB  - The reason(s) for the atherogenic properties of Lp(a) lipoprotein is still
      unclear, and several mechanisms have been studied. Alterations in gene expression
      in endothelial cells (ECs) could be important with respect to risk for coronary
      heart disease (CHD). We have tested the effects of Lp(a) lipoprotein or the
      apolipoprotein of Lp(a) lipoprotein (apo(a)) on cultured human umbilical vein
      endothelial cells (HUVECs) with respect to: (1) the level of endothelin-1 (ET-1)
      mRNA; (2) release of ET-1 into the culture medium; (3) plasminogen activator
      inhibitor-1 (PAI-1) secretion into the culture medium and; (4) total gene
      expression in HUVECs, examined by a polymerase chain reaction (PCR)-based
      technique, differential display-reverse transcription-PCR (DD-RT-PCR). Lp(a)
      lipoprotein reduced the level of ET-1 mRNA as well as the release of ET-1. The
      reduction of ET-1 in the medium was even more pronounced when HUVECs were
      incubated with apo(a), but we found no effect of apo(a) on ET-1 mRNA level.
      Neither Lp(a) lipoprotein nor apo(a) had a significant influence on PAI-1
      secretion. DD-RT-PCR revealed 11 fragments that could represent differences
      between cells exposed or not exposed to Lp(a) lipoprotein. Following subcloning
      and sequencing, 18 sequences that differed between exposed and unexposed cultures
      were obtained. Four of the subcloned fragments have up to now been used as a
      probe for northern blot analyses, and one fragment was confirmed to be regulated
      by Lp(a) lipoprotein. In conclusion, Lp(a) lipoprotein is shown to control ET-1
      mRNA levels and the function of at least one more gene, the nature of which is
      unknown.

PMID- 9520123
TI  - Biogenesis of Lp(a) in transgenic mouse hepatocytes.
AB  - Lipoprotein(a) [Lp(a)] biogenesis was examined in primary cultures of hepatocytes
      isolated from mice transgenic for both human apolipoprotein(a) [apo(a)] and human
      apoB. Steady-state and pulse-chase labeling experiments demonstrated that newly
      synthesized human apo(a) had a prolonged residence time (approximately 60 min) in
      the endoplasmic reticulum (ER) before maturation and secretion. Apo(a) was
      inefficiently secreted by the hepatocytes and a large portion of the protein was
      retained and degraded intracellularly. Apo(a) exhibited a prolonged and complex
      folding pathway in the ER, which included incorporation of apo(a) into high
      molecular weight, disulfide-linked aggregates. These folding characteristics
      could account for long ER residence time and inefficient secretion of apo(a).
      Mature apo(a) bound via its kringle domains to the hepatocyte cell surface before
      appearing in the culture medium. Apo(a) could be released from the cell surface
      by apoB-containing lipoproteins. These studies are consistent with a model in
      which the efficiency of post-translational processing of apo(a) strongly
      influences human plasma Lp(a) levels, and suggest that cell surface assembly may
      be one pathway of human Lp(a) production in vivo. Transgenic mouse hepatocytes
      thus provide a valuable model system with which to study factors regulating human
      Lp(a) biogenesis.

PMID- 9520124
TI  - Analysis of the mechanism of lipoprotein(a) assembly.
AB  - We have assessed the ability of a battery of purified recombinant
      apolipoprotein(a) (r-apo(a)) derivatives to bind to immobilized low-density
      lipoprotein (LDL) by ELISA. Removal of the apo(a) kringle IV type 8 and type 9
      sequences dramatically reduced apo(a) binding to LDL. The binding of apo(a) to
      LDL was effectively inhibited by arginine, lysine, the lysine analogue epsilon
      aminocaproic acid and proline; comparable inhibition was observed using the 17K
      and KIV5-8 r-apo(a) derivatives, suggesting a direct role for sequences contained
      in the latter species in mediating the initial non-covalent interactions which
      precede specific disulfide bond formation. We also determined that r-apo(a) binds
      directly to a synthetic apoB peptide spanning amino acid residues 3732-3745; this
      interaction appeared to be mediated by sequences present in apo(a) kringle IV
      types 8 and 9, and could be inhibited by arginine, lysine and proline. The
      results of this study indicate that the efficiency of Lp(a) assembly is a direct
      function of the initial non-covalent interactions between apo(a) and LDL; in
      addition, these studies suggest that Cys3734 in apoB mediates covalent linkage
      with apo(a) by virtue of the ability of the apoB sequences surrounding this
      residue to directly interact with apo(a) KIV type 9.

PMID- 9520125
TI  - Metabolism of Lp(a): assembly and excretion.
AB  - Lp(a) is one of the most atherogenic lipoproteins, and we know much more about
      the pathophysiology of Lp(a) than about its physiological function and
      metabolism. From our previous investigations and the new results reported here,
      we propose the following model of Lp(a) metabolism: apo(a) is biosynthesized in
      liver cells and the size of the isoform determines its rate of synthesis and
      excretion. Specific kringle-4 domains in apo(a), mainly T-6 and T-7, bind in a
      first step to circulating LDL, followed by the stabilization of the newly formed
      Lp(a) complex by a disulfide bridge. Circulating Lp(a) interacts specifically
      with kidney cells, or possibly other tissues, causing cleavage of 2/3-3/4 of the
      N-terminal part of apo(a) by a collagenase-type protease. Part of the apo(a)
      fragments is found in the urine, but there are indications that they in fact
      represent the biologically active form of apo(a). The core portion of Lp(a) in
      turn is cleared by the LDL-receptor or another specific binding system of the
      liver. Strategies for reducing plasma Lp(a) levels with medication should aim at
      interfering with the assembly of Lp(a) on one hand and the stimulation of apo(a)
      fragmentation on the other hand.

PMID- 9520126
TI  - The lysine-binding function of Lp(a).
AB  - The atherogenicity of Lp(a) is attributable to the binding of its
      apolipoprotein(a) component to fibrin and other plasminogen substrates. It can
      attenuate the activation of plasminogen, diminishing plasmin-dependent
      fibrinolysis and transforming growth factor-beta activation. Apolipoprotein(a)
      contains a major lysine-binding site in one of its kringle domains. Destroying
      this site by site-directed mutagenesis greatly reduces the binding of
      apolipoprotein(a) to lysine and fibrin. Transgenic mice expressing wild-type
      apolipoprotein(a) have a 5-fold increase in the development of lipid lesions, as
      well as a large increase in the focal deposition of apolipoprotein(a) in the
      aorta, compared to the lysine-binding site mutant strain and to non-transgenic
      litter mates. Although the adaptive function of apolipoprotein(a) remains
      obscure, a gene with similar structure has evolved by independent remodeling of
      the plasminogen twice during the course of mammalian evolution.

PMID- 9520127
TI  - Vascular accumulation of Lp(a): in vivo analysis of the role of lysine-binding
      sites using recombinant adenovirus.
AB  - Despite the importance of lipoprotein(a) [Lp(a)] as an atherogenic risk factor,
      very little information, especially from in vivo studies, is available concerning
      which structural features of apo(a) contribute to the interactions of Lp(a) with
      the vessel wall and its proatherogenic properties. Nearly all the proposed and
      proven activities of apolipoprotein(a) [apo(a)] focus on its high degree of
      sequence homology with plasminogen and the possibility that structural features
      shared by these two molecules contribute to the atherogenesis associated with
      high Lp(a) plasma levels in humans. In these studies, we examined the properties
      of three forms of Lp(a) differing at postulated lysine-binding domains contained
      in the constituent apo(a). We used the recombinant adenoviral gene delivery
      system to produce apo(a) in the plasma of human apoB transgenic mice, resulting
      in high levels of Lp(a) similar to those found in the plasma of humans. By
      comparison of in vitro lysine-binding properties of these forms of Lp(a) with
      measurements of Lp(a) vascular accumulation in the mice, we have demonstrated
      that lysine-binding defective forms of Lp(a) have a diminished capacity for
      vascular accumulation in vivo.

PMID- 9520128
TI  - Lipoprotein(a): identification of subjects with a superbinding capacity for
      fibrinogen.
AB  - We have previously shown that the binding of lipoprotein(a) [Lp(a)] to
      immobilized fibrinogen involves the domain located in kringles IV-5 to IV-8, but
      not kringle IV-10. In extending those studies to subjects living in Chicago and
      in the island of Sardinia, we found that about 6% of them had an Lp(a) with Bmax
      values of 27.7+/-6.0 fmol, which were about 5-8-fold higher than those of
      controls (3.4+/-2.8 fmol) and in the range of those observed for free apo(a)
      derived from the Lp(a) of controls (36.6+/-2.9 fmol). This superbinding phenotype
      was unaffected by age, sex, type of lipid disorder and hypolipidemic agents, and
      also had a familial incidence. We are currently exploring the hypothesis that
      this fibrinogen superbinding phenotype is due to conformational changes of
      apolipoprotein(a) [apo(a)] resulting from the lipid content and composition of
      the Lp(a) particle and/or sequence anomalies in the kringle domain IV-5 to IV-8.

PMID- 9520129
TI  - Plasma concentrations of Lp(a) lipoprotein and TGF-beta1 are altered in
      preeclampsia.
AB  - This study was performed to investigate the possible association between
      preeclampsia and the plasma concentrations of Lp(a) lipoprotein and TGF-beta1 in
      a large series of patients. Additionally, correlation between the concentrations
      of these molecules and the severity of preeclampsia or fetal growth retardation
      was evaluated. Following clinical examination and biochemical analyses, both
      electroimmunoassay and RIA technique were used for quantitative determinations of
      plasma Lp(a) lipoprotein. ELISA technique was used to measure the active form of
      TGF-beta1 in plasma of pregnant normotensive and preeclamptic women. We examined
      154 women with preeclampsia (preeclampsia group) and 76 healthy, pregnant
      normotensive women (control group). The preeclampsia group was further divided
      into the following subgroups: mild preeclampsia, severe preeclampsia and
      preeclampsia with fetal growth retardation. Plasma levels of Lp(a) lipoprotein
      were lower in the total preeclampsia group as well as in all preeclampsia
      subgroups (5.45+/-7.41, 5.58+/-8.02, 5.08+/-5.38, and 4.32+/-5.28 mg/dl in the
      total preeclampsia group, and in subgroups with mild preeclampsia, severe
      preeclampsia, and preeclampsia with fetal growth retardation, respectively) than
      in the control group (7.84+/-9.26 mg/dl) as determined by quantitative
      electroimmunoassay. Corresponding results were obtained with a radioimmunoassay
      (166.03+/-200.2 U/l in the total preeclampsia group vs. 229.18+/-257.7 U/l in
      controls). There was good correlation between the two methods used for Lp(a)
      lipoprotein measurement. The differences between controls and the total
      preeclampsia group as well as each preeclampsia subgroup were statistically
      significant by a non-parametric test (one-way Kruskal-Wallis test). Plasma
      concentrations of the active form of TGF-beta1 were increased in all preeclampsia
      subgroups as well as in the total group (5.63+/-1.68 ng/ml) compared to controls
      (4.67+/-1.33 ng/ml). This increase in TGF-beta1 was statistically highly
      significant. Plasma concentrations of Lp(a) lipoprotein and the active form of
      TGF-beta1 did not differ significantly between the preeclampsia subgroups. The
      outcome of this study may suggest involvement of both parameters in the
      pathophysiology of preeclampsia and may substantiate the notion of a
      multifactorial etiology of the disease.

PMID- 9520130
TI  - LDL-unbound apolipoprotein(a) and carotid atherosclerosis in hemodialysis
      patients.
AB  - High lipoprotein(a) [Lp(a)] plasma concentrations, which are genetically
      determined by apo(a) size polymorphism, are directly associated with an increased
      risk for atherosclerosis. Patients with end-stage renal disease (ESRD), who show
      an enormous prevalence of cardiovascular disease, have elevated plasma
      concentrations of Lp(a). In recent studies we were able to show that apo(a) size
      polymorphism is a better predictor for carotid atherosclerosis and coronary
      artery disease in hemodialysis patients than concentrations of Lp(a) and other
      lipoproteins. Less than 5% of apo(a) in plasma exists in a low-density
      lipoprotein (LDL)-unbound form. This "free" apo(a) consists mainly of
      disintegrated apo(a) molecules of different molecular weight, ranging from about
      125 to 360 kDa. LDL-unbound apo(a) molecules are elevated in patients with ESRD.
      The aim of this study was therefore to investigate whether the LDL-unbound form
      of apo(a) contributes to the prediction of carotid atherosclerosis in a group of
      153 hemodialysis patients. The absolute amount of LDL-unbound apo(a) showed a
      trend to increasing values with the degree of carotid atherosclerosis, but the
      correlation of Lp(a) plasma concentrations with atherosclerosis was more
      pronounced. In multivariate analysis the two variables were related to neither
      the presence nor the degree of atherosclerosis. Instead, the apo(a) phenotype
      took the place of Lp(a) and LDL-unbound apo(a). After adjustment for other
      variables, the odds ratio for carotid atherosclerosis in patients with a low
      molecular weight apo(a) phenotype was about 5 (p<0.01). This indicates a strong
      association between the apo(a) phenotype and the prevalence of carotid
      atherosclerosis. Finally, multivariate regression analysis revealed age, angina
      pectoris and the apo(a) phenotype as the only significant predictors of the
      degree of atherosclerosis in these patients. In summary, it seems that LDL
      unbound apo(a) levels do not contribute to the prediction of carotid
      atherosclerosis in hemodialysis patients. However, this does not mean that
      "free", mainly disintegrated, apo(a) has no atherogenic potential.

PMID- 9520131
TI  - High plasma levels of apo(a) fragments in Caucasians and African-Americans with
      end-stage renal disease: implications for plasma Lp(a) assay.
AB  - Apolipoprotein(a) [apo(a)] is a plasma glycoprotein that is highly polymorphic in
      size due to differences in the number of a tandemly arrayed cysteine-rich repeat
      called kringle (K)4 at its N-terminus. Most plasma apo(a) is covalently attached
      to apolipoprotein B-100 and circulates as part of lipoprotein(a) [Lp(a)]. A
      fraction of apo(a) circulates free of lipoproteins. Almost all of the free apo(a)
      consists of fragments containing variable numbers of K4 repeats derived from the
      N-terminal region. Previously we provided evidence suggesting that the apo(a)
      fragments present in human plasma are the source of the apo(a) fragments in human
      urine. If this were the case, it would be expected that plasma levels of
      fragments would be higher in subjects with end-stage renal disease (ESRD). In
      this paper we quantified the levels of apo(a) fragments and plasma Lp(a) in 26
      Caucasian and 26 African-American subjects with ESRD and 52 healthy subjects
      matched for race, sex and the size of the apo(a) isoforms. The plasma levels of
      apo(a) fragments and Lp(a) were both higher in the ESRD subjects. In addition,
      the ratio of apo(a) fragments to total immunodetectable apo(a) was increased in
      ESRD. To determine how much the increase in the apo(a) fragments contributed to
      the increase in plasma Lp(a) in ESRD, the plasma Lp(a) levels were measured
      employing two different anti-apo(a) enzyme-linked immunoabsorption assays
      (ELISA). One assay detected both free and bound apo(a), whereas the other assay
      detected only bound apo(a). Although the plasma levels of apo(a) in the ESRD
      subjects tended to be higher using the assay that detected both fragments and
      full-length apo(a), the increase was modest. Thus, although a greater proportion
      of the apo(a) in ESRD plasma circulates as fragments, most of the elevation in
      plasma levels of Lp(a) associated with renal insufficiency is due to an increase
      in intact Lp(a).

PMID- 9520133
TI  - The genetics of alcoholism: 1997.

PMID- 9520132
TI  - Standardization of Lp(a) measurements.
AB  - The standardization of immunoassays for Lp(a) is a major challenge to clinical
      chemists. In order to establish a reference material acknowledged by the
      International Federation of Clinical Chemistry, the Center of Disease Control and
      possibly the World Health Organization, a working group with participants from
      four continents was put together. With the aid of 34 companies, eight proposed
      reference materials have been tested in the last 3 years and two of them have
      been selected for value assignment. A reference method based on dissociation
      enhanced lanthanide fluorescence immunoassays was therefore developed which gives
      linear and parallel response curves by assaying freshly prepared primary
      reference standards, fresh plasma or serum as well as lyophilized or frozen
      proposed reference material. For value assignment, four laboratories
      simultaneously prepare primary reference standards with known isoforms and
      molecular weights. By assaying the amino acid composition of these primary
      reference standards, the molar concentration which is the basis of value transfer
      to the lyophilized proposed reference material can be calculated. In a final
      step, harmonization of all commercially available Lp(a) kits is to be tested by
      assaying 50 Lp(a) samples with increasing Lp(a) concentrations and varying
      isoforms. We hope to be able in the near future to create a basis for comparable
      results in epidemiological studies in different laboratories and also to help to
      improve future long-term precision in clinical chemical laboratories.

PMID- 9520134
TI  - Schizophrenia genetics at the millennium: cautious optimism.
AB  - As the new millennium approaches, research into the genetic aspects of
      schizophrenia has already made an impressive start toward an integrated model
      which is discovering roles for genetic agents, environmental agents and
      experiences, and chance factors. The best model follows that proposed for
      understanding such complex diseases as coronary artery disease and diabetes.
      Genetic information has come from both genetic epidemiology and molecular
      genetics. Evidence for gene regions on 6p and 8p gives the strongest support for
      harboring schizophrenia susceptibility genes, based on international
      collaborative studies that "generally" replicate one another; evidence for
      regions on 3p, 5q, 9p, 20p, and 22q, while less compelling, will encourage
      focused work. Determining the steps between the regions and the phenotype will
      challenge the next generation of scientists.

PMID- 9520135
TI  - Apolipoprotein E type epsilon4 allele, heritability and age at onset in twins
      with Alzheimer disease and vascular dementia.
AB  - The apolipoprotein E (APOE) epsilon4 allele is a risk factor in Alzheimer disease
      (AD), but not in vascular dementia (VaD). We have investigated whether the
      epsilon4 allele is more common in twin pairs concordant for AD, compared with
      those discordant for AD, and whether the epsilon4 allele is more common in AD
      twins than in VaD twins. In addition, we have investigated the relationship of
      the epsilon4 allele and the age at onset in AD and VaD. APOE genotype was
      analysed in 29 senile demented twin pairs. The epsilon4 allele was associated
      with AD and not with VaD. However, there was no difference in the frequency of
      the APOE epsilon4 allele in concordant (33.3%) and discordant (31.3%) AD
      dizygotic twin pairs. Age at onset in AD was significantly lower in epsilon4
      homozygotes than in individuals with one or no copies of epsilon4 (62.4 vs. 73.5,
      p<0.01). In concordant AD twin pairs, the epsilon4 allele frequency was somewhat
      higher in the twins with earlier onset (41.7% vs. 25%), but the difference was
      not statistically significant. In the VaD group the age at onset was not
      significantly different between individuals with or without epsilon4 in their
      genotypes.

PMID- 9520137
TI  - Airway hyperreactivity elicited by toluene diisocyanate (TDI)-albumin conjugate
      is not accompanied by airway eosinophilic infiltration in guinea pigs.
AB  - Nonspecific airway hyperresponsiveness is present in many patients with toluene
      diisocyanate (TDI)-induced asthma; however, the underlying pathophysiological
      mechanisms of this hyperresponsiveness remain controversial. In the present
      study, we used a guinea pig model to investigate the association of TDI-induced
      airway hyperresponsiveness with eosinophilic airway infiltration, which is widely
      considered to play a key role in the development of allergen-induced
      hyperresponsiveness. Guinea pigs were sensitized by i.d. injections of 10 microl
      TDI on day 1 and day 6. Control animals received saline injections. Two weeks
      after the second injection, airway reactivity to inhaled methacholine and
      specific airway resistance (sRaw) was measured before and at several times after
      inhalation challenge with TDI-GSA (guinea pig serum albumin) conjugates.
      Eosinophils in the airways were detected using enzyme histochemistry and
      quantified using computer-assisted image analysis. TDI-specific IgG1 antibodies
      were found in the blood of TDI-sensitized animals. An immediate increase in sRaw
      was induced in these animals by TDI-GSA challenge; airway hyperresponsiveness to
      methacholine was observed at 6 h and 18 h after TDI-GSA challenge. However, TDI
      GSA challenge did not result in an elevation of eosinophils in the airways,
      compared with control animals. The results suggest that the development of TDI
      induced airway hyperresponsiveness is not dependent upon eosinophil infiltration
      in airways.

PMID- 9520136
TI  - Structure-activity relationships of volatile organic chemicals as sensory
      irritants.
AB  - We used a database of 145 volatile organic chemicals for which the sensory
      irritation potency (RD50) has been reported in mice. Chemicals were first
      separated into two groups: nonreactive and reactive, using Ferguson's rule. This
      rule suggests that nonreactive chemicals induce their effect via a physical (p)
      mechanism (i.e., weak forces or interactions between a chemical and a biological
      receptor). Therefore, appropriate physicochemical descriptors can be used to
      estimate their potency. For reactives, a chemical (c) mechanism (i.e., covalent
      bonding with the receptor) would explain their potency. All chemicals were also
      separated on the basis of functional groups and subgroups into 24
      classifications. Our results indicated that the potency of nonreactive chemicals,
      regardless of their chemical structure, can be estimated using a variety of
      physicochemical descriptors. For reactive chemicals, we identified five basic
      reactivity mechanisms which explained why their potency was higher than that
      estimated from physicochemical descriptors. We concluded that Ferguson's proposed
      rule is adequate initially to classify two separate mechanisms of receptor
      interactions, p vs c. Several physicochemical descriptors can be used to estimate
      the potency of p chemicals, but chemical reactivity descriptors are needed to
      estimate the potency for c chemicals. At present, this is the largest database
      for nonreactive-reactive chemicals in toxicology. Because of the wide variety of
      c chemicals presented, a semi-quantitative estimate of the potency of new, or not
      previously evaluated, c chemicals can be arrived at via comparison with those
      presented and the basic chemical reactivity mechanisms presented.

PMID- 9520138
TI  - Functional and subcellular organelle changes in isolated rat and human
      hepatocytes induced by tetrahydroaminoacridine.
AB  - Tacrine (tetrahydroaminoacridine) is a reversible cholinesterase inhibitor used
      for the treatment of Alzheimer's disease. This drug causes an elevation of serum
      aminotransferases in a limited population of patients. Several in vivo studies
      failed to elucidate the mechanism for the enzyme elevation but previous in vitro
      studies have indicated defects in mitochondrial function. In this study, electron
      microscopic, histochemical, and confocal microscopy techniques were used with
      primary hepatocyte cultures from humans and rats to examine the sequence of early
      cellular changes after tacrine exposure. Changes included ribosome alterations as
      early as 1-2 h following tacrine exposure at concentrations ranging between 0.1
      and 1.0 mM. Mitochondrial membrane potential was also altered as indicated by
      decreased rhodamine 123 uptake with time. Cellular lysosome content increased as
      indicated by increased staining of fluorescein isothiocyanate (FITC)-conjugated
      dextran. The results of acid phosphatase histochemistry correlated with the FITC
      dextran findings. Additionally, tacrine-related degranulation and vesiculation of
      the endoplasmic reticulum paralleled the ribosomal and mitochondrial changes.
      These subcellular changes were reproducible in rat and human hepatocytes, showing
      for the first time that human hepatocytes can be altered by tacrine. The
      molecular mechanism of the organelle changes is unknown at this time. Also, the
      relationship between these subcellular changes in isolated hepatocytes and the
      transaminase elevation noted in human populations treated with tacrine needs to
      be clarified.

PMID- 9520139
TI  - Characterization of the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin in B6C3F1
      and DBA/2 mice following single and repeated exposures.
AB  - Previous studies have demonstrated that repeated (14 day) administration of
      2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) enhances the suppression of humoral
      immunity in DBA/2 (Ah-low responder) mice relative to the effect seen with
      identical cumulative doses after a single treatment (cumulative doses of 4.2,
      14.0, and 42 mg/kg). In the present studies, we have explored this phenomenon
      further by determining the status of several specific parameters, which might
      account for the increase in antibody suppression in the DBA/2 strain following
      repeated TCDD exposures. Included in these studies was the induction of hepatic
      and splenic microsomal 7-ethoxyresorufin-o-deethylase (EROD; P4501A1) activity
      and biodistribution of the administered TCDD into various target organs and
      tissues. Changes in lymphocyte subpopulations within the spleen were also
      assessed by flow cytometry following both single and repeated dosing. All studies
      made use of direct comparisons between DBA/2 (Ah-low responder) and B6C3F1 (Ah
      high responder) female mice. Results of these studies demonstrate that the
      enhanced suppression of humoral immunity in DBA/2 mice following repeated
      exposure to TCDD is not directly associated with increases in liver microsomal
      EROD activity and does not appear to be correlated with changes in the pattern of
      biodistribution or amount of TCDD within the liver or spleen of these animals. In
      contrast, the most significant changes that occurred following repeated dosing in
      either strain were observed in the levels of microsomal EROD activity and immune
      cell ratios within the spleen. This effect was characterized as an increase in
      microsomal EROD activity, and a corresponding reduction in the numbers of a non
      B/non-T cell population in the spleen.

PMID- 9520140
TI  - A peroxisome proliferator-activated receptor-alpha (PPARalpha) cDNA cloned from
      guinea-pig liver encodes a protein with similar properties to the mouse
      PPARalpha: implications for species differences in responses to peroxisome
      proliferators.
AB  - The peroxisome proliferator class of non-genotoxic rodent hepatocarcinogens cause
      hepatocyte DNA synthesis, peroxisome proliferation and liver tumours when
      administered to rats and mice, but fail to induce S-phase or peroxisome
      proliferation in hepatocytes from other species including guinea-pigs, dogs, and
      primates including humans. There are compelling data that implicate a nuclear
      receptor, the peroxisome proliferator-activated receptor-alpha (PPARalpha) as an
      important mediator of the toxic and carcinogenic effects of peroxisome
      proliferators (PPs). We were interested to consider the guinea-pig as a possible
      model for human responses to these compounds. This manuscript describes the
      isolation of a full-length cDNA encoding PPARalpha from guinea-pig liver that is
      closely related to receptors identified previously in mouse, rat and human. RNA
      hybridisation experiments suggested that the livers of the PP-responsive rat and
      mouse contained relatively high levels of PPARalpha transcripts, whereas in human
      and guinea-pig liver PPARalpha mRNA was much less abundant. Functional analyses
      suggested that the guinea-pig PPARalpha was able to be activated by PPs. DNA
      binding studies using in vitro translated proteins showed that the guinea-pig
      receptor was able to bind specifically to DNA in the presence of the retinoid X
      receptor (RXR), and transient transfection assays showed that the guinea-pig
      PPARalpha was capable of being transcriptionally activated in a concentration
      dependent fashion by the PPs Wy-14,643 and nafenopin. Also, in guinea-pig primary
      hepatocyte cultures, a dominant negative repressor of PPARalpha ablated the
      suppression of spontaneous apoptosis by PPs. Taken together, these data show that
      the 'non-responsive' guinea-pig expresses active PPARalpha in the liver at
      reduced levels, and may be a useful model for exploring the mechanisms underlying
      the human response to PPs.

PMID- 9520141
TI  - Inhibition of cell-cell communication by methylsulfonyl metabolites of
      polychlorinated biphenyl congeners in rat liver epithelial IAR 20 cells.
AB  - The effects of three polychlorinated biphenyl (PCB) congeners and their six
      methylsulfonyl (MeSO2)-metabolites on cell communication have been investigated
      in the scrape-loading/dye-transfer assay in IAR 20 rat liver epithelial cells.
      The results demonstrated that at non-cytotoxic concentrations 2,2',4',5
      tetrachlorobiphenyl, 2,2',4',5,5'-pentachlorobiphenyl (2,2',4',5,5'-pentaCB),
      2,2',4',5,5',6-hexachlorobiphenyl (2,2',4',5,5', 6-hexaCB), and their 3- and 4
      MeSO2 derivatives completely inhibited the cell communication within 1 h. 4-MeSO2
      2,2',4',5,5'-pentaCB and 4-MeSO2-2,2',4',5, 5',6-hexaCB appeared to inhibit the
      cell communication at slightly lower concentration than their parental PCB
      congeners and 3-MeSO2 derivatives. The results show that 3- and 4-MeSO2
      derivatives of the PCB congeners tested inhibit gap junction intercellular
      communication at about the same potency as their parental compounds. Since
      inhibition of cell communication is often observed after treatment with many
      tumor promoters, our findings suggest that the metabolites may also act as tumor
      promoters.

PMID- 9520142
TI  - Bioactivation of 2-amino-3-methylimidazo[4,5-f] quinoline (IQ) by prostaglandin H
      synthase.

PMID- 9520143
TI  - Increased systemic toxicity of sarcoma chemotherapy due to combination with the P
      glycoprotein inhibitor cyclosporin.

PMID- 9520144
TI  - Evidence of ABC transporters in fresh tumor cells from patients with ovarian
      cancer.

PMID- 9520145
TI  - Excretion of a fluorescent rapamycin-derivative in proximal kidney tubules is
      mediated by P-glycoprotein.

PMID- 9520147
TI  - Relationship between plasma membrane fluidity and R-verapamil action in CHO
      cells.

PMID- 9520146
TI  - Modulation of morphine-6-glucuronide penetration into the brain by P
      glycoprotein.

PMID- 9520148
TI  - Transporter-mediated pulmonary endothelial uptake of fentanyl.

PMID- 9520150
TI  - Studies of multidrug transport proteins in cells derived from human lung samples.

PMID- 9520149
TI  - Brain concentrations of asimadoline in mice: the influence of coadministration of
      various P-glycoprotein substrates.

PMID- 9520151
TI  - Changes in multidrug transporter protein expression in endothelial cells cultured
      from isolated human brain microvessels.

PMID- 9520152
TI  - The effect of drug lipophilicity on P-glycoprotein-mediated colchicine efflux at
      the blood-brain barrier.

PMID- 9520153
TI  - Validation of a Caco-2 cell monolayer culture for drug transport studies.

PMID- 9520155
TI  - Modulation of P-glycoprotein-mediated multidrug resistance in a doxorubicin
      resistant subline of the human lymphoblastoid cell line CCRF-CEM by
      phosphorothioate antisense oligonucleotides.

PMID- 9520154
TI  - Differential resistance to anthracyclines in P-glycoprotein-expressing human
      hepatoma cells.

PMID- 9520156
TI  - Mechanisms responsible for therapy resistance of acute myelogenous leukemia
      (AML).

PMID- 9520157
TI  - Cell membrane perturbations and vincristine transport in sensitive and resistant
      HL-60 cell lines.

PMID- 9520158
TI  - Modulation of vincristine cytotoxicity by dexverapamil in sensitive and resistant
      HL-60 cell lines as a function of extracellular protein binding.

PMID- 9520159
TI  - In vitro investigations of drug release and penetration--enhancing effect of
      ultrasound on transmembrane transport of flufenamic acid.
AB  - Although topical drugs are usually applied at a convenient site, the target for
      the drug interaction may be systemic. Phonophoresis is the use of ultrasound to
      enhance the delivery of topical applied drugs. The purposes of our study were to
      investigate the in vitro penetration and the in vivo transport of flufenamic acid
      in dependence of ultrasound. Percutaneous absorption studies are performed in
      various in vitro models to determine the rate of drug absorption via the skin. We
      designed a phonophoretic drug delivery system to investigate the influence of
      ultrasound on transmembrane transport of different drugs. We investigated the
      absorption of flufenamic acid in a buffer medium in dependence of ultrasound
      energy and application time. For evaluating membrane penetration of flufenamic
      acid, the concentration range of buffer solution was measured. Ultrasound energy
      was supplied for between 5 and 30 min at a range of intensities up to 1.5 W/cm2,
      energy levels commonly used for therapeutic purpose. The pronounced effect of
      ultrasound on the transmembrane absorption of the drug was observed at all
      ultrasound energy levels studied. The time of application was found to play an
      important role in delivery and transport of drug. Dependent on time, we observed
      a rise of temperature up to 4.5 degrees C. It appears that there was no
      difference between an intensity of 0.3 and 1.5 W/cm2 and the measured drug
      concentrations in solution. The highest penetration was observed at an intensity
      of 1.0 W/cm2 after 30 min. These results were not significantly different from
      concentration measurements after 30 min and 0.5 and 1.5 W/cm2. It seems that the
      arise of drug concentration is caused by effects of temperature and by variation
      of membrane delivery in dependence of temperature. Using this in vitro model we
      note it is possible to compare the transdermal penetration and absorption of
      commercial flufenamic ointment in volunteers.

PMID- 9520160
TI  - Cytokine- and hypoxia-induced lipid peroxidation in astrocytes.

PMID- 9520161
TI  - HIV-1 viral load and CD4 cell count in untreated children with vertically
      acquired asymptomatic or mild disease. Paediatric European Network for Treatment
      of AIDS (PENTA).
AB  - BACKGROUND: Plasma HIV-1 RNA levels are high in vertically infected infants.
      Information in older children is limited, particularly in those who have not
      received antiretroviral therapy. OBJECTIVES: To describe the relationships
      between HIV-1 RNA, age and CD4 cell count in untreated vertically infected
      children. DESIGN: HIV-1 RNA was measured in 70 children [median age, 3.5 years
      (range, 0.4-11.9 years); median CD4 cell count, 881 x 10(6)/l (interquartile
      range, 576-1347 x 10(6) cells/l)] enrolled in a randomized placebo-controlled
      trial comparing immediate with deferred zidovudine in asymptomatic or mildly
      symptomatic vertically infected children (PENTA-1 trial). Short-term variability
      was assessed by comparing HIV-1 RNA at -2 and 0 weeks (prior to randomization).
      The relationship between age and HIV-1 RNA, and CD4 cell count was analysed using
      data from all children prior to randomization and sequential samples from 35
      remaining on placebo for up to 105 weeks, by fitting mixed linear models.
      RESULTS: The within-individual SD in viral load was 0.26 log10 copies/ml. The
      median plasma HIV-1 RNA at enrollment was 4.61 log10 (range, 2.3-6.56 log10
      copies/ml), significantly higher in children aged < or = 2 years (median, 5.23
      log10 copies/ml) than in those aged > 2 years (4.51 log10 copies/ml; P < 0.0001).
      Mean HIV-1 RNA fell by 0.38 log10 copies/ml per year up to 2 years of age, by
      0.21 log10 copies/ml per year from 2 to 4 years of age, and by 0.03 log10
      copies/ml per year from 4 to 6 years of age reaching a nadir of 4.25 log10
      copies/ml at 6 years. Mean log10 CD4 cell count declined steadily with age and
      was not significantly correlated with HIV-1 RNA, although there was some evidence
      that the rate of log10 CD4 cell decline was negatively correlated with the
      initial rate of HIV-1 RNA decline. No mutations associated with resistance to
      zidovudine were observed. CONCLUSIONS: Age is a key factor in the interpretation
      of both viral load and CD4 cell count in vertically infected children.

PMID- 9520162
TI  - Suicidal behaviours, euthanasia and AIDS.

PMID- 9520164
TI  - Chronic exposure of human neurons to quinolinic acid results in neuronal changes
      consistent with AIDS dementia complex.
AB  - OBJECTIVE: Concentrations of quinolinic acid, an N-methyl-D-aspartate agonist,
      are often elevated for long periods of time in the cerebrospinal fluid (CSF) and
      brain tissue of patients with AIDS dementia complex (ADC). This study was
      designed to test the hypothesis that chronic exposure of human neurons to
      quinolinic acid levels equivalent to those in the CSF of ADC patients is
      neurotoxic. DESIGN AND METHODS: Human fetal brain 14-16 weeks post-menses was
      cultured in medium with no detectable levels of quinolinic acid. After 4 weeks,
      350 or 1200 nmol/l quinolinic acid was added to the feeding medium for a further
      5 weeks. Neurotoxicity was evaluated using immunohistochemistry, transmission and
      scanning electron microscopy, and image analysis. RESULTS: A total of 1200 nmol/l
      quinolinic acid caused altered cell associations, a decrease in cell density and
      decreased microtubule-associated protein (MAP)-2 immunoreactivity compared with
      cultures exposed to 350 nmol/l quinolinic acid or controls. Image analysis of
      neurons in randomly selected fields revealed significantly swollen cells (P <
      0.0001) compared with those treated with 350 nmol/l quinolinic acid or controls.
      Dendritic varicosities and discontinuous microtubular arrays were present in
      neurons exposed to both quinolinic acid concentrations, but not in control
      cultures. CONCLUSIONS: This study is the first to assess quinolinic acid levels
      in the experimental medium, and demonstrates that chronic exposure of human
      neurons to concentrations of quinolinic acid equivalent to those in the CSF of
      patients with ADC leads to alterations in dendritic ultrastructure and MAP-2
      immunoreactivity, which is consistent with ADC pathology.

PMID- 9520163
TI  - Inhibition of HIV-1 gp120-induced apoptosis in neuroblastoma SK-N-SH cells by an
      antisense oligodeoxynucleotide against p53.
AB  - OBJECTIVES: This study examines the cytotoxicity potential and the mechanism of
      toxicity of the HIV-1 gp120 on human neuroblastoma cells. DESIGN: Previous data
      from our group have suggested that the HIV-1 envelope protein gp120 promotes the
      secretion of tumor necrosis factor-alpha and other factors by astrocytes and
      microglial cells present in primary human brain cell cultures, thereby
      contributing to the injury of neurons in these cultures. This study investigates
      the cytotoxicity potential and the mechanism of toxicity of gp120 on human
      neuroblastoma cells. METHODS: SK-N-SH cells were treated with HIV-1 gp120, and
      was followed by in situ DNA fragmentation staining and small molecular weight DNA
      extraction studies to ascertain the induction of apoptosis by gp120 in these
      cells. To evaluate a potential role of the growth suppressor gene p53, gp120
      treated SK-N-SH cells were subjected to reverse transcription polymerase chain
      reaction (RT-PCR) and Western blot analyses for the induction of p53. An
      antisense oligodeoxynucleotide against p53 was used to investigate the role of
      p53 in the gp120-induced apoptosis in these cells. RESULTS: Data from T7 DNA
      polymerase staining and small molecular weight DNA extraction studies
      demonstrated that gp120-induced DNA breakage in SK-N-SH cells with fragmentation
      patterns characteristic of apoptosis. RT-PCR and Western blot analyses revealed
      that the gp120-mediated induction of apoptosis was dependent on a gp120-induced
      and gp120-sustained upregulation of p53. The induction of p53 by gp120 was
      specific, since an antibody against gp120 prevented both the induction of p53 and
      subsequent apoptosis in SK-N-SH cells. The critical role of p53 was further
      illustrated by the effectiveness of a p53 antisense oligodeoxynucleotide to
      inhibit the gp120-induced apoptosis. As a control, the apoptosis-inducing
      potential of gp120 on SK-N-SH cells was not seen in the HIV-1 Gag proteins even
      when used at up to 5 nM. CONCLUSIONS: These results established that HIV-1 gp120
      is potentially cytotoxic to human neuronal cells through the induction of p53,
      which may eventually lead to induction of apoptosis.

PMID- 9520165
TI  - Human cytomegalovirus product UL44 downregulates the transactivation of HIV-1
      long terminal repeat.
AB  - OBJECTIVE: Human cytomegalovirus (HCMV) is often isolated from HIV-1-infected
      patients and the two viruses can infect the same cell type giving rise to direct
      bidirectional interactions. Whereas the long terminal repeat (LTR)
      transactivation ability of HCMV immediate early gene (IE1/IE2) is well
      documented, no information is available on the possible role of other HCMV
      proteins. In this study, the activity of ppUL44, an early DNA-binding protein, on
      HIV LTR transactivation was investigated. METHODS: HIV LTR transactivation by
      ppUL44 in presence or absence of HIV-1 Tat and HCMV IE1/IE2 was determined in J
      Jhan and U973 cells through transient transfection experiments with a series of
      different expression vectors. Some experiments were also performed on U373-MG
      astrocytoma cells permanently transfected with UL44 or with another HCMV gene
      used as a control (UL55). RESULTS: The basal transactivation activity of the HIV
      LTR was not influenced by the presence of ppUL44. On the contrary, the
      transactivation observed in the presence of Tat, IE1/IE2 or both factors in
      synergy was strongly downregulated by ppUL44 in a dose-dependent manner. Deletion
      constructs of ppUL44 demonstrated that the region of the molecule responsible for
      the inhibition of the LTR is located within the last 114 amino acids at the
      carboxyl-terminal region. CONCLUSIONS: The results obtained indicate that within
      the last 114 amino acids of ppUL44 there is a domain that has a negative effect
      on the ability of HIV-1 LTR to be activated by both its autologous transactivator
      Tat and the heterologous transactivator HCMV IE1/IE2 functioning individually or
      synergistically.

PMID- 9520166
TI  - Impaired cytokine production by neutrophils isolated from patients with AIDS.
AB  - OBJECTIVES: To determine the ability of neutrophils isolated from HIV
      seropositive patients to produce proinflammatory cytokines. DESIGN: The in vitro
      responsiveness of polymorphonuclear neutrophils (PMN) and peripheral blood
      mononuclear cells (PBMC) to lipopolysaccharide (LPS), used in the presence or
      absence of interferon (IFN)gamma, was determined in 47 HIV-positive patients with
      advanced stages of virus infection. METHODS: Cytokines in cell-free supernatants
      were measured by enzyme-linked immunosorbent assay or radioimmunoassay. RESULTS:
      Cell-free supernatants from PMN isolated from the peripheral blood of HIV
      positive patients and stimulated with LPS contained increased amounts of tumour
      necrosis factor (TNF)-alpha and interleukin (IL)-8 with respect to supernatants
      obtained from PMN of normal donors. In contrast, release of IL-1beta and IL-1ra
      (IL-1 receptor antagonist) in response to LPS, or LPS plus IFNgamma, was found to
      be lower in PMN from HIV-positive patients than in PMN from controls, but was
      significant only in the case of IL-1ra. Furthermore, the release of IL-12 induced
      by LPS or LPS plus IFNgamma did not significantly differ between PMN from HIV
      positive patients and healthy donors. Concerning PBMC, the production of TNF
      alpha and IL-12 in response to LPS, or LPS plus IFNgamma, was found to be
      significantly higher in cells isolated from HIV-positive patients, whereas the
      release of IL-1beta was significantly lower. In the case of IL-8, no
      statistically significant difference was found between PBMC isolated from HIV
      positive patients and healthy donors. CONCLUSIONS: Collectively, the data suggest
      that in HIV-positive patients with advanced stages of disease, the ability of PMN
      to produce specific cytokines in response to LPS is significantly altered.
      Alterations in this ability might contribute to the evolution of HIV disease.

PMID- 9520167
TI  - Does hepatitis C virus co-infection accelerate clinical and immunological
      evolution of HIV-infected patients?
AB  - OBJECTIVE: To study the influence of hepatitis C virus (HCV) co-infection on
      clinical and immunological evolution of HIV-infected patients. DESIGN: A
      longitudinal study of HIV-infected individuals with or without HCV infection,
      identified at the Infectious Diseases Department of Dijon University Hospital and
      enrolled in a historical cohort, was performed. METHODS: One hundred and nineteen
      HIV-infected people co-infected with HCV and 119 matched individuals infected
      with HIV alone were included in the cohort (median participation time 3 years;
      range, 2 months to 11.5 years). Clinical progression was defined as one or more
      of the following: a 30% decrease in the Karnofsky index; a 20% loss of body
      weight; an AIDS-defining illness (for non-AIDS patients); death (except by
      accident, suicide or overdose). Immunological progression was defined as a 50%
      decrease in the initial CD4 T-cell count (for patients with an initial count >
      100 x 10(6) cells/l). Effects of HCV co-infection were evaluated using Kaplan
      Meier survival analysis and significance was tested using univariate (log-rank
      and Peto's tests) and multivariate methods (Cox's model). RESULTS: In univariate
      analysis, immunological progression was not statistically different between the
      HCV-positive group and the HCV-negative group, whereas clinical progression was
      significantly faster in HCV-positive patients (P < 0.005, log-rank test). In a
      multivariate Cox model, clinical progression remained significantly associated
      with infection by HCV [hazard ratio (HR), 1.64; 95% confidence interval (CI),
      1.06-2.55; P < 0.05]. Stratified multivariable analysis retained HCV as a
      significant prognostic factor of clinical progression (HR, 10.9; 95% CI, 1.09
      109.3; P < 0.05) and immunological progression (HR, 2.31; 95% CI, 1.16-4.62; P <
      0.02) for patients with an initial CD4 count above 600 x 10(6) cells/l.
      CONCLUSIONS: Clinical progression is more rapid in HIV-HCV co-infected patients
      than in HIV-seropositive patients are not infected by HCV. The prognostic value
      of HCV infection for both clinical and immunological progression is significant
      at early stages of HIV infection. These findings may argue for active management
      of hepatitis C infection in co-infected individuals, especially for asymptomatic
      patients whose CD4 count is above 600 x 10(6) cells/l, to predict and prevent
      accelerated progression of HCV and HIV diseases.

PMID- 9520168
TI  - Cerebrospinal fluid HIV-1 RNA levels: correlation with HIV encephalitis.
AB  - OBJECTIVE: Neuropathological abnormalities induced by HIV-1 are not always
      predictable on the basis of the presence of HIV-related neurological symptoms.
      HIV-1 RNA load was measured in the cerebrospinal fluid (CSF) of HIV-infected
      patients to verify whether it could be a marker of HIV-induced neuropathology.
      DESIGN AND METHODS: Histopathological and immunohistochemical examination of the
      brain for HIV-1 p24 antigen was performed in 50 HIV-infected patients with
      neurological symptoms; patients were defined as having HIV encephalitis in the
      presence of HIV-related lesions or HIV-1 p24 antigen-positive cells. Quantitative
      polymerase chain reaction for HIV-1 RNA was retrospectively applied to CSF
      samples that had been drawn 1-60 days prior to death from these 50 patients;
      paired plasma samples of 28 patients were also analysed. RESULTS: The CSF HIV-1
      RNA copy numbers were significantly higher in 22 patients with HIV encephalitis
      than in 28 patients without (median, 4.77 log10 versus 3.45 log10 copies/ml; P =
      0.0003). No correlation was found between CSF HIV-1 RNA load and the presence of
      opportunistic brain pathologies at post-mortem examination or between HIV-1 RNA
      loads in paired CSF and plasma samples. CONCLUSIONS: High CSF HIV-1 RNA levels
      are associated with HIV encephalitis, regardless of the presence of opportunistic
      brain diseases or HIV-1 RNA levels in plasma. Quantitative CSF HIV-1 RNA may
      therefore be used as a specific marker of HIV-induced neuropathology.

PMID- 9520169
TI  - Short-term evolution of HIV-1 viraemia and CD4+ cell counts in patients who have
      a primary mutation to zidovudine.
AB  - OBJECTIVE: To investigate the different responses to antiretroviral treatment
      including zidovudine, of patients harbouring HIV with primary resistance to
      zidovudine, serum viral load, and CD4+ cell counts, for 24 weeks in a group of
      antiretroviral-naive patients with the codon 215 mutation of the HIV pol gene and
      in a control group at the start of treatment. DESIGN: A case-control
      retrospective study (1989-1996). METHOD: Nineteen out of 210 patients previously
      studied harboured the codon 215 mutation, had a self-reported compliance with
      treatment, a minimum follow-up of 24 weeks, and were treated with zidovudine
      alone or in combination with other nucleoside analogues. These patients were
      matched with 19 patients with wild-type strains at entry by initial CD4+ cell
      counts, clinical status, and antiretroviral treatment. RESULTS: During the first
      12 weeks, CD4+ cell counts increased (76+/-26 and 64+/-26 x 10(6)/l in wild-type
      and mutant virus-infected groups, respectively), decreasing slightly until week
      24, although no significant differences were found between the two groups
      studied. Serum viral load decreased in both groups (change in serum viral load of
      0.80+/-0.11 log10 and 0.87+/-0.26 log10 copies/ml, wild-type and mutant virus
      infected, respectively), although no significant differences were found between
      groups. CONCLUSION: No significant differences were found between patients with
      the primary mutation to zidovudine and control patients harbouring wild-type
      virus in terms of short-term response measured by serum viral load and CD4+ cell
      counts.

PMID- 9520170
TI  - Reduction of the viral load of HIV-1 after the intraperitoneal administration of
      dextrin 2-sulphate in patients with AIDS.
AB  - OBJECTIVE: To determine the safety and efficacy of the sulphated polysaccharide,
      dextrin 2-sulphate, when delivered to the lymphatic circulation by the peritoneal
      route. DESIGN: An open Phase I/II dose-escalation clinical study in which six
      patients with AIDS were treated with seven courses of dextrin 2-sulphate each
      lasting 1 month. METHODS: During each course of treatment, the drug was
      administered daily for 28 days using an intraperitoneal catheter. Viral load was
      measured at frequent intervals using a plasma tissue culture infectious dose
      (TCID) assay, a cellular TCID assay, p24 antigenaemia, HIV-1 RNA and HIV-1 DNA.
      Plasma beta-chemokine levels were also measured. RESULTS: Dose escalation was
      completed without toxicity. A total of 7 patient-months of treatment were
      completed. With increasing doses of dextrin 2-sulphate, the infectious plasma
      viraemia, cellular viraemia and p24 antigenaemia all fell during the period of
      drug administration, but with no significant change in HIV-1 RNA. This was
      associated with increased plasma levels of macrophage inflammatory protein (MIP)
      1alpha and MIP-1beta. Dextrin 2-sulphate accumulated in peritoneal macrophages
      and induced the release of MIP-1alpha and MIP-1beta from these cells in vitro.
      These beta-chemokines could have augmented the cell surface-mediated anti-HIV-1
      effect of dextrin 2-sulphate in vivo by binding to and blocking the CC-chemokine
      receptor-5. A second fall in infectious plasma viraemia, cellular viraemia, p24
      antigenaemia and HIV-1 RNA was seen at day 100 which was then sustained for
      several months. A clinical improvement in Kaposi's sarcoma was also seen.
      CONCLUSIONS: Our results suggest that the intraperitoneal administration of
      dextrin 2-sulphate can reduce the replication of HIV-1 in patients with AIDS.
      With increasing doses of dextrin 2-sulphate, the fall in viral load was seen
      during the period of drug administration and again 2 months after completing
      treatment.

PMID- 9520171
TI  - Treatment of HIV-related fluconazole-resistant oral candidosis with D0870, a new
      triazole antifungal.
AB  - OBJECTIVES: To evaluate the efficacy and tolerance of D0870 in the treatment of
      HIV-related fluconazole-resistant oro-oesophageal candidosis. DESIGN: Multicentre
      open study. PATIENTS: HIV-seropositive patients with oro-oesophageal candidosis
      despite at least 7 days of treatment with fluconazole at doses of 100 mg per day
      or more. METHODS: Patients received an initial dose of D0870 (150 mg), then 25 mg
      per day for 6 days. Symptoms and signs of candidosis were compared at entry and
      on days 3 and 7 of treatment. At each visit, samples were taken for safety
      monitoring and for in vitro susceptibility testing of Candida isolates. Limited
      pharmacokinetic samples were taken on days 1 and 7. RESULTS: Of 26 evaluable
      patients, 16 showed partial improvement, nine showed no improvement, and only one
      had full clearance of thrush by day 7. In vitro testing of the cleared patient's
      isolate suggested that it was susceptible to fluconazole. Symptoms of dysphagia
      cleared in 14 and improved in five of the 22 patients with presumptive
      oesophageal involvement at entry. Pharmacokinetic measurement showed wide
      variability in maximum D0870 levels recorded on day 1 (range, 0.07-0.34 mg/l) and
      susceptibility testing of isolates also showed a range of minimal inhibitory
      concentration values to D0870 (range, < 0.06-8 mg/l; median, 0.25 mg/l). When
      these data were combined with clinical response there was a strong suggestion
      that lack of symptomatic improvement was related to low plasma D0870 levels or to
      the presence of less D0870-susceptible isolates. Six patients were noted to have
      a fall in haemoglobin, three of whom were receiving concomitant therapy known to
      suppress bone marrow. Three patients reported headaches as adverse events that
      were attributed to study medication, but D0870 was well tolerated overall.
      CONCLUSIONS: D0870 shows promise in the treatment of fluconazole-resistant oro
      oesophageal candidosis and was well tolerated, although efficacy in this
      difficult-to-treat patient group was probably limited due to the inadequate
      plasma levels achieved in this pilot study with the low doses of D0870
      administered.

PMID- 9520172
TI  - The relationship of clinic experience with advanced HIV and survival of women
      with AIDS.
AB  - OBJECTIVE: Hospital and physician experience have been linked to improved
      outcomes for persons with HIV. Because many HIV-infected patients receive care in
      clinics, we studied clinic HIV experience and survival for women with AIDS.
      DESIGN: Retrospective cohort study of women with AIDS whose dominant sources of
      care were clinics. Clinic HIV experience was estimated as the cumulative number
      of Medicaid enrollees with advanced HIV who used a particular clinic as their
      dominant provider up to the year of the patient's AIDS diagnosis: low experience
      (< 20 patients), medium (20-99 patients), high (> or = 100 patients).
      Proportional hazards models examined relationships between experience and
      survival. SETTING: A total of 117 New York State clinics. PATIENTS: A total of
      887 New York State Medicaid-enrolled women diagnosed with AIDS in 1989-1992. MAIN
      OUTCOME MEASURE: Survival after AIDS diagnosis. RESULTS: In later study years
      (1991-1992), patients in high experience clinics had an approximately 50%
      reduction in the relative hazard of death (0.53; 95% confidence interval, 0.35
      0.82) compared with patients in low experience clinics. Adjusting for demographic
      and clinical variables, 71% of patients in high experience clinics were alive 21
      months after diagnosis compared with 53% in low experience clinics. Experience
      and survival were not significantly associated in the early study years (1989
      1990). CONCLUSIONS: In more recent years, women with AIDS receiving care in high
      experience clinics survived longer after AIDS diagnosis than those in low
      experience clinics, providing further evidence of a relationship between provider
      HIV experience and outcomes.

PMID- 9520173
TI  - HIV infection and risk factors among female sex workers in southern Vietnam.
AB  - OBJECTIVES: To determine the extent of HIV infection among female commercial sex
      workers (CSW), to identify risk factors, and to provide baseline data for
      developing and targeting prevention measures. SUBJECTS AND METHODS: A total of
      968 female CSW were enrolled in a cross-sectional study from August 1995 to
      October 1996. Information was obtained from confidential face-to-face interview,
      physical examination, and laboratory testing. RESULTS: A total of 65.5% of female
      CSW reported inconsistent condom use. Overall seroprevalence was 5.2%. The
      highest seroprevalence (9.5%) was detected in An Giang province, a border area
      adjacent to Cambodia. Out of seven HIV isolates in An Giang province, six were
      characterized as Thai subtype E and one as subtype B. Multiple logistic
      regression analysis showed an independent significant association between HIV
      seroprevalence and the following: age < or = 30 years [odds ratio (OR), 5.1; 95%
      confidence interval (CI), 1.7-15.2]; high frequency of sex (> 20 times per week;
      OR, 13.5; 95% CI, 3.6-50.2); inconsistent condom use (OR, 2.8; 95% CI, 1.01-8.0;
      sign of genital ulcers (OR, 18.1; 95% CI, 1.8-182); venereal warts (OR, 9.0; 95%
      CI, 2.5-33.0); brothels as sex venue (OR, 7.0; 95% CI, 2.0-24.3); and working at
      the border area (OR, 5.1; 95% CI, 2.4-11.0). Brothels as work-sites were
      significantly related to inconsistent condom use and the socioeconomic background
      of clients. Only 0.5% of CSW reported injecting drug use. CONCLUSIONS: Female CSW
      at brothels who reported inconsistent condom use and ulcerous sexually
      transmitted disease, particularly in the border area with Cambodia, had greater
      risk of HIV infection. Brothels were more frequently used as sex venues in the
      border area and were more likely to be visited by occasional clients who were
      difficult to access. Drug use among female CSW in this region was rare. The
      development of prevention measures should be based on these results.

PMID- 9520175
TI  - Profound and unanticipated anemia with lamivudine-zidovudine combination therapy
      in zidovudine-experienced patients with HIV infection.

PMID- 9520174
TI  - Safety evaluation of nonoxynol-9 gel in women at low risk of HIV infection.
AB  - OBJECTIVE: To determine the safety of a vaginal microbicide, COL-1492, containing
      52.5 mg nonoxynol-9, applied once daily for 14 days among healthy volunteers.
      METHODS: A randomized, double-blind controlled trial with three arms, COL-1492
      gel versus placebo gel versus no-treatment controls, was conducted. Outcomes of
      interest were reported genital symptoms, incidence of gynaecological signs, and
      incidence of genital lesions revealed by colposcopy. Participants were enrolled
      in four centres (Belgium, The Netherlands, and two in Thailand). RESULTS: A total
      of 534 women participated in the study: 179 used COL-1492, 178 used placebo, and
      177 were no-treatment controls. Study visits were scheduled 1 week prior to
      enrollment (day -7), day 0 (enrollment), day 8 and day 14. The most frequently
      reported genital symptom was vaginal discharge in both the COL-1492 and placebo
      groups. This appeared to be related to leakage of the product out of the vagina.
      The incidence of lesions associated with epithelial disruption (ulcers and
      abrasions) was very low (< 2%) and there was no statistically significant
      difference between the three groups. Of the lesions observed by colposcopy that
      did not involve epithelial disruption, petechial haemorrhage was the most
      frequently detected, with an incidence of 20.1, 9.0 and 7.3% in the COL-1492,
      placebo and control groups, respectively. COL-1492 users had a higher incidence
      of erythema (8.4 versus 2% in the other groups). CONCLUSION: COL-1492 showed
      minimal toxicity when applied once daily. A Phase III trial to assess the
      product's effectiveness in HIV prevention is currently ongoing.

PMID- 9520176
TI  - Indinavir-induced renal failure.

PMID- 9520177
TI  - Is the combination of hepatitis and indinavir potentially dangerous?

PMID- 9520178
TI  - Quick and easy detection of cytomegalovirus retinitis using conjunctival swab and
      polymerase chain reaction in AIDS patients.

PMID- 9520179
TI  - CCR-5 genotype and sexual transmission of HIV-1.

PMID- 9520180
TI  - Molecular epidemiology characterization of a multidrug-resistant Mycobacterium
      bovis outbreak amongst HIV-positive patients.

PMID- 9520181
TI  - Is it necessary to conduct trials with trimethoprim-sulphamethoxazole amongst HIV
      infected individuals in Africa?

PMID- 9520184
TI  - Lesbian sex and risk of HIV transmission.

PMID- 9520183
TI  - Progressive multifocal leukoencephalopathy regression with highly active
      antiretroviral therapy.

PMID- 9520182
TI  - Reduction in oropharyngeal candidiasis following introduction of protease
      inhibitors.

PMID- 9520185
TI  - Serologic testing of cornea donors.
AB  - PURPOSE: To review the current requirements and rationale for serologic testing
      of cornea donors and to provide guidelines for dealing with results of
      nonrequired tests. METHODS: Eye Bank Association of America (EBAA) and Food and
      Drug Administration (FDA) regulations are examined with respect to current
      knowledge of the risk of donor-to-host transmission of systemic infectious
      diseases via corneal transplantation. RESULTS: Negative screening tests are
      required for human immunodeficiency virus (HIV) 1 and 2, hepatitis B surface
      antigen (HBsAg), and hepatitis C virus (HCV) before release of tissue for
      transplantation. Other tests reported by organ-procurement organizations commonly
      include hepatitis B core antibody (anti-HBc), syphilis, cytomegalovirus (CMV),
      and human T-lymphotropic virus (HTLV) I and II. No systemic infectious-disease
      transmission from donor corneas supplied by EBAA-member eye banks has occurred in
      the last 12 years, a period during which >400,000 corneas were provided for
      transplantation. CONCLUSION: EBAA donor-screening requirements, including
      serologic testing, have resulted in an excellent safety record. Requirements for
      serologic testing should continue to be regularly reviewed as new information
      becomes available.

PMID- 9520186
TI  - Repair of Descemet's membrane detachment with perfluoropropane (C3F8)
AB  - PURPOSE: To report the use of perfluoropropane (C3F8) gas in the repair of
      Descemet's membrane detachments. METHODS: Descemet's membrane detachments after
      cataract surgery in three eyes and pars plana vitrectomy in a fourth underwent
      anterior-chamber gas-exchange descemetopexy with an isoexpansile 14% mixture of
      C3F8 to facilitate reattachment of Descemet's membrane. RESULTS: Descemet's
      membrane detachment was successfully reattached after anterior-chamber gas
      exchange with 14% C3F8 in three of the four eyes treated. The fourth eye treated
      with 14% C3F8 probably failed Descemet's membrane reattachment because of an
      unrecognized viscoelastic bleb situated anterior to Descemet's membrane. No
      corneal decompensation or fluctuations in intraocular pressure were believed to
      be attributable to isoexpansile C3F8 gas exchange. CONCLUSION: Early recognition
      and repair of Descemet's membrane detachments may prevent complications, such as
      corneal decompensation, corneal opacities and edema, and an overall decline in
      visual acuity. Isoexpansile C3F8 is demonstrated as a safe and efficacious
      alternative for the repair of Descemet's membrane detachment.

PMID- 9520187
TI  - Emergence of penicillin-resistant Streptococcus pneumoniae ocular infections.
AB  - BACKGROUND: Approximately 15-20% of Streptococcus pneumoniae clinical isolates in
      the United States are not susceptible to penicillin. Isolates with a minimum
      inhibitory concentration (MIC) of 0.12-1.0 mg/ml are intermediately resistant,
      and those with an MIC > 2.0 microg/ml are classified as having high-level
      penicillin resistance. PURPOSE: We determined the proportion of penicillin
      resistant S. pneumoniae recovered from ocular and periocular infections from 1976
      through 1995, compared these cases with penicillin-susceptible controls, and
      evaluated the susceptibility of penicillin-resistant isolates to selected
      cephalosporins and fluoroquinolones. METHODS: MICs for cephalothin, ceftazidime,
      ciprofloxacin, and ofloxacin were determined for available isolates by the E
      test. We performed a case-comparison study to evaluate differences between
      patients with penicillin-susceptible and -nonsusceptible ocular pneumococcal
      infections. RESULTS: Of 173 ocular isolates of S. pneumoniae isolated in the 20
      year period, 12 (7%) were not susceptible to penicillin, including eight (5%)
      intermediate isolates and four (2%) highly resistant isolates. Penicillin
      intermediate and -resistant pneumococci were recovered at a rate of none of 46
      isolates from 1976 through 1980, one (4%) of 25 from 1981 through 1985, one (2%)
      of 51 from 1986 through 1990, and 10 (20%) of 51 from 1991 through 1995 (p <
      0.0004). We found no significant differences in presenting characteristics
      between patients with ocular infections due to penicillin-susceptible pneumococci
      and those caused by nonsusceptible strains. All retested isolates with
      intermediate susceptibility to penicillin had a cephalothin MIC < or = 1.5
      microg/ml, and all retested isolates with high-level penicillin resistance had a
      cephalothin MIC > or = 4 microg/ml. The ceftazidime MIC for all penicillin
      resistant isolates was > or = 24 microg/ml. All penicillin-nonsusceptible
      isolates had MICs < or = 1.5 microg/ml for ciprofloxacin and < or = 3 microg/ml
      for ofloxacin. CONCLUSION: Penicillin resistance has recently emerged among
      ocular S. pneumoniae. Cephalothin, ciprofloxacin, and ofloxacin have good
      activity against some ocular isolates with intermediate penicillin
      susceptibility, although another agent such as vancomycin may be needed for
      pneumococci with high-level penicillin-resistance.

PMID- 9520188
TI  - Role of presensitization and donor-recipient crossmatching in corneal graft
      outcome.
AB  - PURPOSE: A positive donor-recipient crossmatch (CM) due to preexisting recipient
      lymphocytotoxic antibodies is known to be an important factor in allograft
      failure in the majority of organ transplantations. However, the effect of
      positive CM on corneal graft outcome is less known. METHOD: Between 1982 and
      1994, CM was performed by the microlymphocytotoxicity method using donor
      lymphocytes and recipient pretransplant serum in 759 consecutive corneal
      transplantations (maximal follow-up, 36 months). Patients were evaluated
      regarding the type of allospecificity of antibodies involved and their role on
      corneal graft outcome (rejection and failure). RESULTS: A positive CM was found
      in 61 patients (8%) and a negative CM in 698 patients (92%). The positive and
      negative CM groups had similar graft rejection rates at 36 months. Patients with
      a positive CM due to antibodies directed against donor human leukocyte antigen
      (HLA) (as defined on the basis of private and public or CREG HLA allele
      specificities) did not have an increased risk of rejection. However, patients
      with positive CM and presensitization (previous graft or rejection history) had a
      statistically significant increase in risk of corneal endothelial rejection.
      CONCLUSION: This study shows that donor-recipient CM could be a useful procedure
      for the selection of recipients for corneal transplantation in patients
      presensitized by anterior graft or previous corneal rejection.

PMID- 9520189
TI  - Bacterial load and protein deposits on 15-day versus 1-day disposable hydrophilic
      contact lenses.
AB  - PURPOSE: This study quantified the bacterial load and protein deposits on 1- and
      15-day disposable contact lenses after use in normal wearers. METHODS: Sixteen
      patients were randomly assigned to a 1-day contact lens (1-Day Acuvue) in one eye
      and to a 15-day contact lens (Acuvue) in the contralateral eye. Only one
      specified solution was allowed for the care of 15-day lenses. All patients were
      evaluated every month for 6 months (at times T1, T2, T3, T4, T5, T6). At times
      T1, T3, and T5, the lenses were removed in a sterile fashion and sent for
      laboratory quantification of Staphylococcus aureus and Pseudomonas aeruginosa. At
      T2, T4, and T6, quantification of protein deposits was determined, and at T0 and
      T6, impression cytology of the conjunctiva was performed. RESULTS: P. aeruginosa
      was not identified on any lens. At T1, T3, and T5, S. aureus was significantly
      greater on the 1-day versus 15-day lenses (p < 0.001). In contrast, protein
      deposits were significantly greater on the 15-day lenses at all time points (T2,
      T6: p < 0.01; T4: p < 0.05). Impression cytology of the 15-day lens eyes revealed
      a worsening trend compared to the 1-day lens; however, no statistically
      significant differences were found between the two groups (p = 0.29). CONCLUSION:
      Results of this study suggest that the use of cleaning and preservative solutions
      can alter the ocular surface bacterial environment of the contact lens wearer and
      that these changes are not a direct consequence of contact lens wear. The
      bactericidal activity of these solutions could, with time, also affect ocular
      surface cells, leading to contact lens intolerance and ocular surface disease.

PMID- 9520190
TI  - Endothelial cell density and contact lens-induced corneal swelling.
AB  - PURPOSE: To determine the relationships among endothelial morphometric variables
      and contact lens-induced corneal swelling in a homogeneous sample of adapted
      contact-lens wearers. METHODS: Fifteen male subjects ranging in age from 20 to 40
      years, all adapted to daily wear of hydrogel lenses, wore uniform-thickness
      lenses (Dk/L = 5.78) under unilaterally patched eyes for 4 h. Unpatched fellow
      eyes served as controls. Central corneal thickness was measured with an optical
      pachometer. Central endothelial images were obtained with a Topcon SP-1000
      Specular Microscope and analyzed by the Topcon IMAGEnet processing system.
      Thickness and morphometric data were collected on test and control eyes before
      and after the patching sessions. RESULTS: A strong correlation (r = -0.795; p <
      0.001) was found between central corneal swelling and endothelial-cell density.
      Correlations between swelling and the coefficient of variation in cell area (r =
      0.502; p < 0.06) and between swelling and the percentage of six-sided cells (r = 
      0.200; p < 0.48) were not significant. Correlations among the morphometric
      variables were not significant. Differences in the morphometric variables between
      test and control eyes were not significant before or immediately after the
      patching sessions. CONCLUSION: Endothelial-cell density is useful in explaining
      differences in corneal-swelling responses to closed-eye contact-lens wear among
      adapted wearers, whereas morphometric variables based on cell-size variability
      and shape are not.

PMID- 9520191
TI  - Alterations in blood-aqueous barrier after corneal refractive surgery.
AB  - PURPOSE: To assess alterations in the blood-aqueous barrier after radial
      keratotomy (RK), photorefractive keratectomy (PRK), laser in situ keratomileusis
      (LASIK), and phototherapeutic keratectomy (PTK). METHODS: Aqueous flare was
      evaluated using the Kowa FM 500 laser flare meter in a total of 87 eyes from 82
      patients who underwent refractive surgery. Measurements were obtained
      preoperatively in 51 eyes of 51 patients who underwent RK or PRK and again at the
      end of surgery, and at 1 day and 1 week postoperatively. These patients had been
      randomized (double masked) to receive topical 0.1% dexamethasone, polymyxin B
      (6,000 U/ml), and 0.5% neomycin 4 times a day for 1 week after surgery, or
      polymyxin B (6,000 U/ml) and 0.5% neomycin for 1 week. Aqueous flare measurements
      were also obtained before surgery in 36 eyes (31 patients) that underwent LASIK
      and again at 1 day and 1 and 2 weeks postoperatively. All patients in this group
      received topical 0.1% dexamethasone, polymyxin B (6,000 U/ml), and 0.5% Neomycin
      4 times a day for 15 days after surgery. RESULTS: Uneventful RK induced a
      significant increase in flare immediately after surgery, although this did return
      to baseline 1 day after surgery (Friedman test). Measurements at 7 days after
      surgery were similar in steroid-treated and untreated groups. Limbal bleeding,
      which occurred in 23% (12/51) eyes, did not induce significantly increased flare
      as compared to uneventful RK. Microperforations, which occurred in 18% (9/51)
      eyes, did induce significant alterations in the blood-aqueous barrier that
      persisted for >1 day, but measurements returned to preoperative levels by day 7.
      PRK and LASIK induced substantially increased flare in some eyes.
      Phototherapeutic keratectomy, in particular, induced an elevation in flare
      measurements that did not return to normal levels even by 15 days after surgery
      (Friedman test). CONCLUSIONS: Using mean results of laser flare meter evaluation,
      uneventful RK appears to induce short-lasting elevations in aqueous flare in both
      steroid-treated and untreated patients. Microperforation induced prominent
      alterations in flare measurements, although limbal bleeding did not. Both PRK and
      LASIK did appear to increase flare measurements in some eyes, while PTK induced
      significant elevations in aqueous flare in the majority of eyes.

PMID- 9520192
TI  - Peters' anomaly associated with protruding corneal pseudo staphyloma.
AB  - PURPOSE: To describe a new manifestation of Peters' anomaly. METHODS: We managed
      four infants with an unusual form of Peters' anomaly. One eye of each patient had
      a thickened and scarred cornea, mimicking a corneal staphyloma, protruding
      anteriorly from the corneal plane. The other eye of each patient ranged from
      normal to having severe ocular anomalies. A corneal transplant was performed in
      each case. RESULTS: Follow-up ranged from 1 to 3 years. Three eyes maintained
      graft clarity for at least 1 year. Each of these eyes developed vision. Two of
      these eyes developed glaucoma. The one eye with graft failure developed an
      inoperable retinal detachment. The histopathology of each corneal button showed
      changes consistent with Peters' anomaly. CONCLUSIONS: These corneas demonstrated
      characteristics of both Peters' anomaly and congenital anterior staphyloma.
      Despite their severe anomalies, surgery successfully restored a more normal
      cosmetic appearance in all four eyes and vision in three eyes.

PMID- 9520193
TI  - Lamellar intrastromal corneal tattoo for treating iris defects (artificial iris)
AB  - PURPOSE: Defects in the iris are associated with clinically significant optical
      anomalies, such as glare and peripheral light scatter; however, current
      artificial-iris technology remains inadequate. The purpose of this study was to
      explore the practicality of a lamellar intrastromal tattoo technique as a
      treatment modality to correct optical and cosmetic defects resulting from
      simulated iris abnormalities in eye-bank eyes. METHODS: Simulated iris defects
      (abnormally large pupil, sector iridectomy, iridodialysis, and aniridia) were
      produced in a series of eye-bank eyes. Depending on the simulated iris defect,
      one or two lamellar channel(s) were created at 50% depth of the cornea via a
      peripheral incision (1.8 mm) with specialized proprietary instruments
      (KeraVision, Inc., Fremont, CA, U.S.A.). Commercially available tattoo pigment
      was inserted through the lamellar channel(s) and blended into the defective
      region of the iris. RESULTS: The tattoo treatment was relatively simple to
      perform. Tattoo pigment was inserted uniformly through the small incision, and
      adequate color blending to match the recipient iris was achieved. The
      intrastromal tattoo effectively obscured light. CONCLUSION: The lamellar
      intrastromal tattoo technique appeared to be efficacious for treating different
      types of iris defects in eye-bank eyes. Further investigation of this technique
      in nonsighted patient eyes is warranted.

PMID- 9520194
TI  - Depth predictability of stromal pockets in the posterior cornea.
AB  - PURPOSE: To evaluate the predictability of the depth of stromal pockets made in
      the posterior cornea for the excision of anterior or posterior lamellar corneal
      buttons with a planned thickness. METHODS: Stromal corneal pocket dissections
      were created in human eye bank eyes by making a peripheral arcuate keratotomy
      incision at 60, 80, or 95% of central pachymetry and creating a pocket from the
      bottom of the incision across the cornea. Pocket depth was measured by pachymetry
      immediately after surgery and by light microscopy. RESULTS: Mean achieved central
      pocket depth differed by 0.03+/-0.03 mm from the intended depth. Variation in
      depth across the pocket decreased from 0.07+/-0.02 mm for pockets made at 60% of
      the intended depth to 0.05+/-0.01 mm for pockets made at 80% depth, and 0.04+/
      0.02 mm for pockets made at 95% depth (p < 0.01). Pachymetric and histological
      measurements of relative pocket depth averaged 64+/-9% and 73+/-7%, respectively,
      for pockets made at 60% of the intended depth, 82+/-7% and 86+/-3% for pockets
      made at 80% depth, and 91+/-7% and 92+/-3% for pockets made at 95% depth. The
      difference between pachymetric and histological relative pocket depth
      measurements decreased with deeper pocket depth (p < 0.01). CONCLUSIONS: In the
      posterior cornea, stromal pockets can be created to within 30 microm from the
      intended depth. Variation in depth throughout the pocket decreases with deeper
      pocket depth. Pachymetry is a reliable method to check the achieved pocket depth
      during surgery; the accuracy of pachymetry readings improves with deeper pocket
      depth.

PMID- 9520195
TI  - Keratocyte repopulation in epikeratoplasty specimens.
AB  - PURPOSE: To study the histology and pattern of keratocyte repopulation of
      surgically removed human epikeratoplasty lenticules. METHODS: Removed
      epikeratoplasty lenticules and penetrating keratoplasty buttons that contained
      epikeratoplasty lenticules were evaluated for duration of epikeratoplasty,
      histologic and ultrastructural features, and average number of keratocytes per
      high-power microscopic field. The keratocyte density was compared with age
      matched controls. RESULTS: Fifteen epikeratoplasty specimens from eight
      penetrating keratoplasties and seven removed lenticules were reviewed. The
      indications for keratoplasty were myopia, keratoconus, and aphakia. The
      lenticules were in place for 7-120 months, and the keratocyte count ranged from
      14 to 40 per high-power field. Keratocyte density increased to 30-40 per high
      power field, similar to age-matched controls, at approximately 48 months
      postoperatively, similar to the density of the controls. Keratocytes appeared to
      have migrated from the periphery to the center of the lenticules. CONCLUSIONS:
      Normal keratocyte density in epikeratoplasty lenticules is reached by
      approximately 48 months after surgery.

PMID- 9520196
TI  - Effects of ciprofloxacin, streptomycin, and gentamicin on rabbit corneal
      transendothelial electrical potential difference.
AB  - PURPOSE: A previous report suggested that high concentrations of ciprofloxacin in
      the anterior chamber may cause dose-dependent acute corneal decompensation.
      Therefore we evaluated the effect of varying concentrations of ciprofloxacin in
      the anterior chamber on the corneal endothelium and compared these effects with
      those of gentamicin and streptomycin. METHODS: We assessed endothelial transport
      function by determining transendothelial electrical potential differences (TEPDs)
      of rabbit corneas. Our control solution was bicarbonate-buffered balanced saline
      with glucose (BSG), to which we added ciprofloxacin (50, 100, 125, and 150
      microg/ml), gentamicin (1,000 and 2,000 microg/ml), and streptomycin (196, 437,
      and 696 microg/ml). RESULTS: At high concentrations exceeding minimal inhibitory
      concentrations against 90% of common ocular isolates (MIC90), accelerated decay
      of TEPDs was seen with all three antibiotics. Adverse effects on TEPDs were noted
      at concentrations corresponding to >50 times MICs with ciprofloxacin and 40 x
      MICs with gentamicin, but only 2 times MICs with streptomycin. CONCLUSION: Our
      study shows that concentrations of ciprofloxacin, gentamicin, and streptomycin
      below or equal to their MIC90 levels do not adversely affect endothelial
      transport function in a rabbit model.

PMID- 9520197
TI  - Topical use of zinc desferrioxamine for corneal alkali injury in a rabbit model.
AB  - PURPOSE: To evaluate the efficacy of topical zinc desferrioxamine in acute
      corneal alkali injury in rabbits. METHODS: Twenty rabbits were anesthetized and a
      standardized alkali burn (1N NaOH) was performed in the center of the cornea (7.5
      mm diameter). The animals were randomly divided into two groups and treated
      (double-masked) with topical zinc desferrioxamine, 220 microM, (group 1) or its
      vehicle (group 2). Drops were applied 7 times/day for 28 days. Topical
      gentamicin, 0.3%, was instilled twice a day. Animals were evaluated twice a week.
      At each examination (using the slit-lamp), the depth of corneal ulcer was graded
      as follows: 0, no ulcer; 1, tissue loss less than one third of corneal thickness;
      2, one third to two thirds tissue loss; 3, more than two thirds tissue loss; 4,
      descemetocele; or 5, perforation. Ulceration area, vascularization, and
      epithelial defects also were measured. RESULTS: During the study period, the
      grading of mean corneal ulcerations in group 1 ranged from 0.2 to 1.00, whereas
      in group 2, it ranged from 1.4 to 2.7. The mean grade and area of ulceration in
      group 2 were greater than those in group 1 (p < 0.05). CONCLUSION: Topical zinc
      desferrioxamine may be an adjunctive treatment in protecting the cornea against
      induced alkali injury.

PMID- 9520198
TI  - Experimental use of tetrodotoxin for corneal pain after excimer laser
      keratectomy.
AB  - PURPOSE: To determine the duration of anesthesia, effect on corneal
      reepithelialization, and systemic toxicity of topical tetrodotoxin (TTX)
      administered after excimer laser keratectomy. METHODS: Two groups of six rabbits
      each underwent excimer laser keratectomy in the right eye to create a 5-mm
      diameter wound, 75 mm in depth. One group then received a 40-microl aliquot of
      topical 1 mM TTX into the injured eye, whereas the other group received 40 microl
      of the sodium citrate vehicle as a control. The rabbits were treated with TTX or
      vehicle again at 6, 12, 18, and 24 h. Corneal sensation was tested at 3, 6, 9,
      12, 15, 18, 21, 24, 30, 32, and 40 h. To determine whether TTX inhibited corneal
      reepithelialization, compared with vehicle-treated control eyes, the healing rate
      of the epithelial defect was measured. RESULTS: Administration of TTX every 6 h
      for 24 h produced nearly complete anesthesia for > or = 30 h. At 32 h, 8 h after
      the final application of TTX, there was still significant anesthesia of the TTX
      treated corneas (p = 0.0325, Wilcoxon test). Normal corneal sensation in all TTX
      treated animals returned at 40 h, or 16 h after the final dose. In contrast,
      vehicle-treated eyes all had normal sensation for nearly the entire duration of
      the experiment. At 40 h, the TTX-treated eyes had slightly larger defects than
      vehicle-treated eyes, 7.85+/-1.74 versus 4.54+/-1.31 mm2 (p < 0.025, t test).
      However, at 49 h and thereafter, both groups were equally healed (p > 0.05, t
      test). No systemic toxicity was observed in any of the rabbits. CONCLUSION:
      Topical TTX is a long-acting and nontoxic local anesthetic in a rabbit model of
      excimer laser keratectomy.

PMID- 9520199
TI  - Analysis of human ocular mucus: effects of neuraminidase and chitinase enzymes.
AB  - PURPOSE: Our goal was to establish the characteristic migration pattern on sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of high molecular
      weight mucins from human ocular mucus and the effects of treatment with exo- and
      endoglycosidases. METHODS: Chromatography by gel filtration with Sepharose CL-4B
      was performed on samples collected from normal subjects. Human ocular mucins from
      the high molecular weight fraction were digested with exoglycosidases
      (neuraminidase, N-acetyl-beta-D-glucosaminidase, beta-D-glucosidase) and
      endoglycosidases (chitinase, lysozyme); and the resulting products were analyzed
      by electrophoresis. Carbohydrate identification was performed using lectin
      probes. RESULTS: The migration of the ocular mucins on SDS-PAGE stopped after
      treatment with neuraminidase, which removes the terminal negatively charged
      sialic acid residues from mucin. Chitinase (beta(1-4)N-acetylglucosaminidase)
      treatment increased the electrophoretic migration of mucins. Staining with wheat
      germ agglutinin and Maackia amurensis agglutinin lectins showed that these mucins
      contain beta(1-4)NAcGlc and SAa(2-3)Gal linkages. CONCLUSIONS: These studies
      demonstrate that the mobility of human ocular mucins on SDS-PAGE is determined by
      their intrinsic total negative charge and is not dependent on SDS treatment. It
      is interesting to note that human ocular mucus contains chitinous material
      resistant to lacrimal lysozyme, which is accessible to chitinase, an enzyme now
      found to degrade human ocular mucins. These chitinous linkages could be in part
      responsible for the mucus resistance.

PMID- 9520200
TI  - Management of primary corneal graft failure.
AB  - PURPOSE: We report two patients with primary graft failure (PGF) from a mutual
      donor. The surgery in each case was done by a different surgeon experienced in
      penetrating keratoplasty (PK). The cases were managed differently in the
      postoperative period with good visual results in both cases. We discuss the
      various management options available when confronted with apparent PGF in the
      early postoperative period. METHODS: Both patients had excessive graft edema and
      haze in the immediate postoperative period. Case 1 received a repeat graft after
      4 weeks because there was no improvement in graft clarity despite intensive
      topical steroids. In case 2, repeat surgery was deferred with ultimate gradual
      improvement in the clarity of the graft over a period of 6 months. RESULTS: Both
      patients obtained clear grafts with a visual acuity of 20/30 at 15 months after
      surgery. CONCLUSION: Primary graft failure is a rare complication of PK. Repeat
      PK is the most definitive therapeutic alternative, although some grafts may clear
      without any additional surgery. We suggest all cases of PGF be observed for > or
      = 3-4 weeks for signs of graft clearing before proceeding with a repeated PK.

PMID- 9520201
TI  - Post-corneal transplant tumors of nondonor origin in the anterior chamber of the
      eye: a case report.
AB  - PURPOSE: To investigate whether post-corneal transplant tumors are of donor
      origin, we studied the case of a 29-year-old female corneal transplant recipient
      who developed tumors in the anterior chamber on the iris of her right eye 7 years
      after transplantation. METHODS: Because the corneal graft donor was a 53-year-old
      man whose cause of death was reported as heart failure but who had uremia
      secondary to a metastatic Grawitz's tumor, transmission of his malignancy had to
      be excluded. One of the patient's iris tumors was removed through an incision in
      the cornea for examination to establish the diagnosis. RESULTS: The histological
      examination of the iris mass showed the typical picture of a noncaseous
      epithelioid cell granuloma compatible with the diagnosis of sarcoidosis. The
      observed post-corneal transplant tumor was clearly not of donor origin.
      Nevertheless, when tumor growth is observed in an eye after corneal
      transplantation, transmission of a malignancy has to be excluded. To the best of
      our knowledge, this is the first report of sarcoidosis with iris nodules after
      corneal transplantation. CONCLUSION: Our case report illustrates the importance
      of keeping reliable medical histories of graft donors and of their use in
      establishing whether post-transplant tumors are of donor origin. The long-term
      storage of donor medical records should be recommended because of the importance
      of being able to access that information even years after transplantation.

PMID- 9520202
TI  - Histopathology of recurrent gelatinous drop-like corneal dystrophy.
AB  - PURPOSE: To elucidate more fully the histopathology of gelatinous drop-like
      corneal dystrophy in a case that recurred and was operated on 7 years after the
      original surgery. METHODS: Transmission electron microscopy, including the use of
      cuprolinic blue to image sulfated proteoglycans, and horseradish peroxidase as a
      marker for in vitro epithelial permeability. RESULTS: Our patient's epithelium
      was often abnormally thick, and many intercellular spaces were present at all
      levels, although cell-cell contact via desmosomes was also evident. Horseradish
      peroxidase, when used as an in vitro tracer, was able to penetrate the most
      superficial tight junctions of the corneal epithelium. Basal epithelial cells
      were not columnar, and numerous spike-like projections protruded into the
      underlying amyloid/collagenous tissue from the basal epithelium. Beneath this,
      duplication of a discontinuous epithelial basement membrane was noted. In this
      region, collagen often coexisted with amyloid, the deposition of which was
      extensive. As in some other corneal pathologies, long-spacing collagen was
      detected. The association of small proteoglycans with collagen was unremarkable,
      although some abnormally large, sulfated proteoglycan filaments were interspersed
      with the amyloid and underlying stroma. CONCLUSION: Recurrent gelatinous drop
      like corneal dystrophy shares several histopathologic features with its primary
      counterpart, although some features, such as the presence of abnormally large,
      sulfated proteoglycans and long-spacing collagen, the permeability of the
      epithelial tight junctions, and the duplication of the epithelial basement
      membrane, have not been reported previously.

PMID- 9520203
TI  - Clinical features of bleb disorder of the cornea.
AB  - BACKGROUND: Bleb disorder of the cornea is a rare corneal epithelial disorder
      that has previously been described in asymptomatic patients or those with
      recurrent nontraumatic corneal erosions. METHODS: We report two cases of bleb
      disorder, each presenting with blurred vision from irregular astigmatism
      secondary to the bleb changes. We also report on the detection of bleb disorder
      in siblings. RESULTS: Both patients underwent surgical debridement of the
      epithelium with resolution of symptoms on epithelial resurfacing. CONCLUSION: The
      diagnostic clues, inheritance pattern, differential diagnosis, and treatment
      options of bleb disorder of the cornea are discussed.

PMID- 9520204
TI  - Bilateral corneal ulcers in primary vitamin A deficiency.
AB  - PURPOSE: To report a case of bilateral corneal ulcers and perforations resulting
      from hypovitaminosis A in an alcoholic patient. METHODS: A 38-year-old cachetic
      man presented with bilateral corneal ulcerations and severe visual loss. He was
      hospitalized, developed bilateral corneal perforations, and was treated with
      bilateral corneal transplants. RESULTS: Serum vitamin A level was 0.01 microg/dL
      (normal, 0.30-0.75). The electroretinogram was consistent with vitamin A
      deficiency. His clinical status improved after vitamin A replacement.
      CONCLUSIONS: Although rare in developed countries, the ophthalmologist must
      consider avitaminosis A in the differential diagnosis of corneal ulcerations in
      cachetic, alcoholic, or chronically ill patients. Early diagnosis and treatment
      can prevent unwanted outcomes.

PMID- 9520205
TI  - Mycobacterium chelonei masquerading as Corynebacterium in a case of infectious
      keratitis: a diagnostic dilemma.
AB  - PURPOSE: The diagnosis of Mycobacterium keratitis can often be missed both
      clinically and microbiologically and this report highlights one such case.
      METHODS: Review of medical and microbiological records. RESULTS: We report a case
      of Mycobacterium keratitis in a 25-year-old man that was misdiagnosed as
      Corynebacterium keratitis at initial presentation. Presence of partially stained
      and beaded bacilli in a Gram-stained smear of repeat corneal scrapings raised the
      suspicion of an unusual organism. Ziehl-Neelsen staining of the decolorized Gram
      stained smear and subculture on Lowenstein-Jensen medium helped us to establish
      the diagnosis. CONCLUSIONS: A high degree of suspicion needs to be maintained,
      especially in cases in which (a) there is a history of corneal trauma involving a
      foreign body, (b) the Gram-stained smear of corneal scrapings shows a paucity of
      organisms and the presence of partially stained and beaded bacilli in the
      presence of confluent growth of colonies resembling those of Corynebacterium, and
      (c) a typical corneal feature like "cracked windshield" stromal lesion is seen,
      to avoid such a misdiagnosis. Inclusion of a Lowenstein-Jensen culture at the
      initial presentation, especially when the clinical presentation is atypical, as
      seen in this case, will lead to an early diagnosis.

PMID- 9520206
TI  - Recurrent endophthalmitis after cataract surgery with a scleral-tunnel incision.
AB  - PURPOSE: To present a case of recurrent postoperative endophthalmitis with a
      scleral-tunnel abscess and adjacent microbial keratitis. METHODS: A 76-year-old
      woman with microbial keratitis and recurrent endophthalmitis after cataract
      surgery was referred to a tertiary care center for further management. The
      medical chart of the patient was reviewed. RESULTS: The patient was seen on the
      eighth postoperative day with endophthalmitis that responded to medical
      treatment. Initial vitreous cultures were negative. The endophthalmitis recurred
      after the medical treatment was discontinued. She subsequently developed
      microbial keratitis at 1 o'clock adjacent to the limbus. Cultures from the site
      of corneal abscess and vitreous grew coagulase-negative Staphylococcus.
      Gonioscopy revealed the presence of a scleral abscess, which responded to
      subconjunctival injection of vancomycin and an intense and prolonged course of
      topical antibiotics. CONCLUSION: A scleral abscess should be suspected in a
      patient with endophthalmitis or microbial keratitis or both after a scleral
      tunnel incision for cataract surgery.

PMID- 9520207
TI  - Pellucid marginal corneal degeneration 12 years after penetrating keratoplasty
      for keratoconus.
AB  - PURPOSE: To report visually disabling postkeratoplasty astigmatism occurring 12
      years after a corneal transplant for keratoconus apparently caused by pellucid
      marginal corneal degeneration (PMD). METHODS: A 33-year-old woman had had a
      corneal transplant for keratoconus in her left eye. Twelve years later, she was
      referred for evaluation and management of increasingly blurred vision due to
      marked postkeratoplasty astigmatism. RESULTS: The donor cornea protruded over a
      region of thinning, anterior to and concentric with a thinned inferior wound.
      Videokeratoscopy showed +18.35 D of astigmatism in the 34 degree meridian and
      inferior corneal steepness surrounding the region of inferior flatness.
      CONCLUSION: To our knowledge, this is the first case of apparent PMD occurring
      after corneal transplantation for keratoconus. The presence of subtle
      biomicroscopic and keratoscopic signs of PMD prior to corneal transplantation for
      keratoconus may affect the planned surgical approach.

PMID- 9520208
TI  - Topical anesthetic abuse and ring keratitis.

PMID- 9520209
TI  - Color reversal-learning deficits after tectofugal pathway lesions in the pigeon
      telencephalon.
AB  - Pigeons were post-operatively trained to discriminate two colors presented
      simultaneously. After reaching criterion on this task, they were required to
      perform a series of reversals of the color discrimination in which the positive
      and negative consequences of the stimuli were interchanged. Lesions of
      ectostriatum (the telencephalic target of the avian tectofugal visual pathway)
      impaired the ability of pigeons to learn a color-reversal task. An examination of
      the pattern of sparing and loss of performance on this task after lesions of
      various components of the ascending visual pathways suggests that deficits in
      color-reversal learning observed after lesions of the visual Wulst are not due to
      the Wulst's connections with the thalamofugal pathway. Instead, the data suggest
      that the visual Wulst maintains a role in color-reversal learning through its
      connections with the tectofugal pathway.

PMID- 9520210
TI  - Behavioral hierarchy in the medicinal leech, Hirudo medicinalis: feeding as a
      dominant behavior.
AB  - The effect of feeding behavior on other behaviors (swimming, crawling and
      shortening) was investigated in the leech, Hirudo medicinalis. The stimulus
      locations and intensities required to produce mechanically elicited behaviors
      were first determined in the non-feeding leech. Stimuli were delivered while the
      leech was in various body positions to determine whether stimulus location
      affected behavioral response. Response thresholds were determined for the
      mechanically elicited behaviors. The same stimuli were then applied to feeding
      leeches to determine if response thresholds had changed. A solution with NaCl and
      arginine was used to elicit feeding. The same sets of stimuli were applied at
      intervals for an hour after feeding, to determine the duration of feeding-induced
      changes in behavior. Depending on the body position and stimulus location,
      stimuli produced different combinations of behaviors that included shortening,
      swimming and crawling. Anterior stimuli generally elicited shortening, whereas
      posterior stimuli generally elicited crawling and swimming, with swimming more
      likely to ventral stimulation than to dorsal stimulation. Having the front sucker
      attached changed these behavioral patterns. During feeding, the response
      thresholds changed dramatically, from 3-5 V to greater than 9 V. This increase in
      threshold began with the start of feeding, even before ingestion commenced.
      Suppression of the behaviors lasted up to 1 h after the end of feeding, with the
      effect on swimming being the most pronounced and longest lasting.

PMID- 9520211
TI  - Intraseptal injections of 192 IgG saporin produce deficits for strategy selection
      in spatial-memory tasks.
AB  - The involvement of the cholinergic septohippocampal system in strategies used to
      reach a spatial goal was examined by functionally inactivating this system with
      infusions of 192 IgG saporin, a potent cholinergic immunotoxin. Rats were
      initially trained on a win-shift radial arm maze (RAM) task and then given
      injections of either 192 IgG saporin (LES) or saline vehicle (CON) into the
      medial septum and vertical limb of the diagonal band. Rats were then retested
      postoperatively on the RAM to assess whether allocentric spatial strategies used
      to solve the task were impaired. The results indicated that injections of 192 IgG
      saporin into the septum of rats produced deficits in allocentric strategies used
      to locate the spatial goal when retested. In addition, place and response
      learning was also examined in a modified version of the Morris water maze task.
      In this task, rats with cholinergic lesions were mildly impaired in their ability
      to learn a place response. In order to clarify further whether rats may have been
      relying on allocentric or egocentric learning strategies to locate the platform,
      a probe trial was given on the final test day in which the visible platform was
      moved to a new location. Control rats swam either to the new platform location or
      the old platform location indicating the use of both an allocentric and
      egocentric response. However, rats with the cholinergic septal lesions swam to
      the new platform location indicating an egocentric response. Taken together,
      these results suggest that selective cholinergic lesions of the septum produce
      deficits in spatial strategies used to locate a spatial goal.

PMID- 9520212
TI  - Recovery of spatial performance in the Morris water maze following bilateral
      transection of the fimbria/fornix in rats.
AB  - The present study investigated whether spatial performance in the Morris water
      maze (MWM) recovers after bilateral transection of the fimbria/fornix (FF) in
      rats, whether such recovery results from restored or residual spatial cognitive
      capacity, and what contribution, if any, pre-operative training makes to such
      recovery. Following surgery, rats were administered extensive training to a
      constant submerged platform location with frequent probe tests to assess
      performance strategies. Following the attainment of asymptotic performance
      levels, rats were tested for acquisition of a second platform location. FF
      lesions were found to produce a severe impairment both in pre-operatively trained
      rats (a retention or retrieval deficit) and in naive rats (an acquisition
      deficit) as shown by the use of indirect routes to the platform on submerged
      platform trials and an absence of localized searching in the platform's area on
      probe trials. However, with further training, performance recovered in both
      groups, such that they eventually used direct escape routes to the submerged
      platform and showed highly localized searching in its area on probe trials. When
      tested for acquisition of a second platform location, a substantial deficit
      reappeared, but was again overcome with additional training. Pre-operative
      training was found to attenuate the initial post-operative deficit and speed
      recovery of performance but did not affect asymptotic performance levels nor
      acquisition of the second platform location. These data show that, though spatial
      cognition as assessed in the MWM is impaired by FF lesions, spatial performance
      eventually recovers. Moreover, pre-operative training, though of some initial
      post-operative benefit, is not essential for this recovery. The deficit shown in
      acquisition of the second platform location argues against recovery of spatial
      cognition and suggests that the basis of recovered performance is residual
      spatial cognitive capacity. Several limitations of this residual capacity are
      apparent: (i) rate of acquisition of spatial information is reduced; (ii)
      utilization of spatial information stored pre-operatively is restricted; and
      (iii) translation of spatial information into navigational behaviour is less
      efficient. The neural bases of this residual system are speculated to include
      spared intra-hippocampal storage mechanisms and/or mechanisms involved in extra
      hippocampal long-term memory consolidation while the neural bases of the FF's
      contribution to spatial information storage in the intact brain are speculated to
      involve theta synchronization of hippocampal activity and the induction and
      expression of hippocampal long-term potentiation.

PMID- 9520213
TI  - Effects of unilateral removal of basal forebrain cholinergic neurons on cued
      target detection in rats.
AB  - Corticopetal cholinergic neurons in the basal forebrain (BF) were removed
      unilaterally from rats by infusing the cholinergic immunotoxin 192 IgG-saporin
      into the substantia innominata. After 2 weeks, the rats with right-hemisphere
      infusions showed signs of visuospatial neglect for targets in the left visual
      field in a cued visual target detection task based upon human covert orienting
      procedures. No behavioral effects were evident 4-6 weeks post-infusion. Ten to 22
      weeks post-infusion all rats responded more quickly and less accurately to
      targets in the visual field contralateral to the infusion than to targets
      ipsilateral to the infusion: further, accuracy for contralateral targets
      decreased with increasing time between trial initiation and target presentation
      (target delay), whereas accuracy for ipsilateral targets increased with target
      delay. Cues did not affect responding to targets in the contralateral visual
      field more than to targets in the ipsilateral field. The changes in performance
      could not be attributed to sensory or mnemonic impairment or to response bias.
      The temporal characteristics of response accuracy and latency suggest the
      competitive interaction of two time-dependent processes: an attentional process
      which relies upon cholinergic input from the BF, and a response preparation
      process which is normally inhibited by the attentional process. These results
      suggest a role for corticopetal cholinergic pathways in maintaining attention to
      salient stimuli by inhibiting subcortical motor circuits.

PMID- 9520214
TI  - Excitotoxic lesions of the subthalamic nucleus ameliorate asymmetry induced by
      striatal dopamine depletion in the rat.
AB  - We investigated the effect of unilateral dorsal striatal dopamine depletion (by
      intrastriatal infusion of 6-OHDA), ibotenic acid lesions of the subthalamic
      nucleus (STN) and combined dopamine depletion and STN lesions on sensorimotor
      asymmetry using a test of somatosensory asymmetry [T. Schallert et al.,
      Pharmacol. Biochem. Behav. 16 (1982) 455-462]. The unilateral striatal dopamine
      depletion resulted in a somatosensory asymmetry. This asymmetry was ameliorated
      in the rats with combined dopamine depletion and STN lesion. indicating the
      potential beneficial nature of STN inactivation in rats with striatal dopamine
      depletion.

PMID- 9520215
TI  - Exploring interlimb constraints during bimanual graphic performance: effects of
      muscle grouping and direction.
AB  - Past studies on bimanual coordination have revealed a general preference to move
      the limbs in a symmetrical fashion, also denoted as the in-phase mode. Its
      counterpart, the asymmetrical or anti-phase mode, is performed with lower degrees
      of accuracy and stability. This ubiquitous tendency to activate the homologous
      muscle groups is referred to as the muscle grouping constraint (egocentric
      constraint). The present study confirmed the generalizability of this constraint
      across various coordination patterns, performed in the horizontal plane. In
      addition, evidence was generated that movement direction in extrinsic space also
      constrains bimanual coordination (allocentric constraint). Overall, the present
      observations suggest that direction is an important movement parameter that is
      encoded in the central nervous system and that is subject to interactions between
      the neural specifications of both limbs.

PMID- 9520216
TI  - Endogenous oxytocin is involved in short-term olfactory memory in female rats.
AB  - To investigate the involvement of oxytocin in their short-term lasting olfactory
      memory performance, adult female Wistar rats (n = 12) were tested for their
      juvenile discrimination abilities. As measured by their exploratory behavior
      towards juveniles, the adult rats were able to discriminate between a previously
      exposed juvenile and a novel one as long as the interval between the two
      exposures was less than 180 min. This ability was maintained across all days of
      the estrous cycle and was unaffected by intracerebroventricular administration of
      synthetic oxytocin (1 ng/5 microl Ringer's solution) or Ringer's solution
      immediately after the first exposure. However, treatment with the oxytocin
      receptor antagonist des-Gly-NH2 d(CH2)5[Tyr(Me)2Thr4]OVT interfered with the
      ability to establish this kind of olfactory memory although the vasopressin V1
      receptor antagonist d(CH2)5Tyr(Me)AVP (100 ng/5 microl each) via the same route
      did not. This suggests that within a narrow range of concentrations endogenous
      oxytocin, but not vasopressin, is critically involved in short-term olfactory
      memory for juvenile conspecifics in female rats. These data are discussed in the
      light of sexual dimorphic brain development.

PMID- 9520218
TI  - Individual to collaborative cognition: a paradigm shift?

PMID- 9520217
TI  - A mental route to motor learning: improving trajectorial kinematics through
      imagery training.
AB  - There are contrasting reports upon the level of effectiveness of motor imagery in
      learning new motor skills, but there is general consensus that motor imagery can
      lead to improvements in performance, especially in combination with physical
      practice. In the present study we examined the effectiveness of motor imagery in
      the acquisition of movement invariants in two grapho-motor trajectorial learning
      tasks with differing visuospatial components: 'Ideogram drawing' and 'connecting
      circles'. Two subject groups were studied: An imagery group, which underwent 10
      min of motor imagery training and a control group, which practised a control
      visuomotor task over the same period of time. The results showed that imagery
      training alone enabled the subjects to achieve a significant approach to movement
      isochrony as well as a significant shifting of peak velocity toward the target.
      After a practice phase, both groups improved their performance, but the imagery
      group was still significantly faster than the control group. Furthermore, a
      series of tests measuring visual imagery abilities was administered to the
      subjects. There were however no significant relationships between the motor
      performance and the visual imagery ability levels of the subjects. It is
      concluded that motor imagery can improve the acquisition of the spatio-temporal
      patterns of grapho-motor trajectories and that there are different processes
      involved in visual and motor imagery.

PMID- 9520219
TI  - A study of collaboration among medical informatics research laboratories.
AB  - The InterMed Collaboratory involves five medical institutions (Stanford
      University, Columbia University, Brigham and Women's Hospital, Massachusetts
      General Hospital, and McGill University) whose mandate has been to join in the
      development of shared infrastructural software, tools, and system components that
      will facilitate and support the development of diverse, institution-specific
      applications. Collaboration among geographically distributed organizations with
      different goals and cultures provides significant challenges. One experimental
      question, underlying all that InterMed has set out to achieve, is whether modern
      communication technologies can effectively bridge such cultural and geographical
      gaps, allowing the development of shared visions and cooperative activities so
      that the end results are greater than any one group could have accomplished on
      its own. In this paper we summarize the InterMed philosophy and mission, describe
      our progress over 3 years of collaborative activities, and present study results
      regarding the nature of the evolving collaborative processes, the perceptions of
      the participants regarding those processes, and the role that telephone
      conference calls have played in furthering project goals. Both informal
      introspection and more formal evaluative work, in which project participants
      became subjects of study by our evaluation experts from McGill, helped to shift
      our activities from relatively unfocused to more focused efforts while allowing
      us to understand the facilitating roles that communications technologies could
      play in our activities. Our experience and study results suggest that occasional
      face-to-face meetings are crucial precursors to the effective use of distance
      communications technologies; that conference calls play an important role in both
      task-related activities and executive (project management) activities, especially
      when clarifications are required; and that collaborative productivity is highly
      dependent upon the gradual development of a shared commitment to a well-defined
      task that leverages the varying expertise of both local and distant colleagues in
      the creation of tools of broad utility across the participating sites.

PMID- 9520220
TI  - Development of systems for support of collaboration in health care: the design
      arenas.
AB  - To explore the design of computer-supported collaborative work in health care, a
      case study is described addressing the social contexts and conditions influencing
      the development process. The data set covers 13 consecutive meetings held in a
      systems design group over a 2-year period, in total approximately 24 h of video
      recordings. Subjectivist methods are used for the data analyses. The results
      suggest that the development of computer-supported collaborative work in health
      care is situated at three social arenas: the societal arena, the organizational
      arena and the workplace arena. These are visited by the design group in patterns
      which correspond to the micro-, meso- and macro-level social structures involved
      in the design. The study displays that longitudinal analyses of design meeting
      dialogues provide the opportunity of improving the understanding of external
      influences on design processes in health care.

PMID- 9520222
TI  - Distributed cognition and knowledge-based controlled medical terminologies.
AB  - Controlled medical terminologies (CMTs) are playing central roles in clinical
      information systems and medical knowledge resource applications. As these
      terminologies grow, they are able to support more complex tasks but require more
      intensive efforts to create and maintain them. Several terminologies are evolving
      into knowledge bases of medical concepts. The knowledge they include is being
      used to support distributed cognition in two forms: complex medical decisions
      involving multiple people and applications, and coordination of maintenance of
      the terminologies themselves.

PMID- 9520221
TI  - Electronic communication and collaboration in a health care practice.
AB  - Using cognitive evaluation techniques, this study examines the effects of an
      electronic patient record and electronic mail on the interactions of health care
      providers. We find that the least structured communication methods are also the
      most heavily used: face-to-face, telephone, and electronic mail. Positive
      benefits of electronically-mediated interactions include improving communication,
      collaboration, and access to information to support decision-making. Negative
      factors include the potential for overloading clinicians with unwanted or
      unnecessary communications.

PMID- 9520223
TI  - Designing computer-based frameworks that facilitate doctor--patient
      collaboration.
AB  - A current trend in medicine involves establishing collaborative problem solving
      between patients and physicians in order to involve patients more in their own
      care. Neither diagnosis nor therapy can be completely successful unless the
      patient and the doctor understand each other and collaborate with each other in
      an effort to gauge the other's requests, needs and concerns. This is made even
      more difficult by the fact that there is often a big difference between the
      doctors and patients in terms of expectations, vocabulary used, and other
      factors. For diagnosis of many disorders, a detailed description of the problem
      and of the patient's history are required. For therapy, patients must understand
      how and when to take prescribed drugs, what changes to make in diet, exercise, or
      lifestyle and why they are important. This paper describes a model of
      asynchronous collaboration between people with very different knowledge of
      medicine in which a computer framework attempts to mediate between patients and
      physicians and reduce some of the differences in communication. It allows
      patients to pace themselves in familiarizing themselves with the relevant domain
      terms, some of the medical factors underlying the conditions under question, and
      the justifications and implications of the prescribed treatment plan. It also
      allows physicians to request more information of patients and gives patients
      contextual information to help them understand the underlying reasons for the
      questions. This framework has been partially implemented in the domain of
      migraines. As described in the paper, not only is the system designed to
      cooperate with the patient, but using the system also results in better mutual
      understanding between the doctor and the patient, thus leading to better
      collaboration between them.

PMID- 9520224
TI  - The neurochemistry of central pain: evidence from clinical studies, hypothesis
      and therapeutic implications.
AB  - Recent evidence suggests that central pain, i.e., pain due to central nervous
      system damage, may be due to a deranged neurotransmission between the sensory
      thalamus and sensory cortical areas. Central pain can be controlled either by
      opposing glutamate neurotransmission or potentiating GABAergic transmission. It
      is speculated that a relative hypofunction of the GABAergic inhibition both at
      thalamic and cortical levels leads to a sectorial excitatory hypertonus in those
      same areas. A blend of the two should mark each patient. A pharmacological
      dissection approach is provided that should optimize the treatment, up to now
      globally poor, of central pain.

PMID- 9520225
TI  - Long-term alleviation of allodynia-like behaviors by intrathecal implantation of
      bovine chromaffin cells in rats with spinal cord injury.
AB  - Adrenal chromaffin cells produce analgesic substances, such as catecholamines and
      enkephalins, and intrathecal (i.t.) implantation of either allografted adrenal
      tissue or xenogenic chromaffin cells produce antinociception in animals. We
      evaluated the analgesic effect of bovine chromaffin cells in a model of central
      pain in which rats exhibit chronic allodynia-like behavior after photochemically
      induced ischemic spinal cord injury. Bovine chromaffin cells or endothelial cells
      were injected i.t. onto the lumbar spinal cord and their effects on mechanical
      and cold allodynia-like behaviors were studied for up to 8 weeks. The chronic
      allodynia-like behavior was stable for months without signs of remission and i.t.
      implantation of human endothelial cells did not alleviate the chronic allodynia
      like behavior for the entire observation period. In contrast, 2 weeks after i.t.
      implantation of bovine chromaffin cells, the mechanical allodynia was abolished
      in the spinally injured rats, and the enhanced response to cold stimuli was
      significantly reduced. The overall effects were significant up to 8 weeks after
      i.t. implantation, although the anti-allodynic effect decreased towards the end
      of the observation period. No signs of side-effects were noted after i.t.
      implantation. The allodynia-like state was temporarily restored by naloxone (0.5
      mg/kg) or phentolamine (0.3 mg/kg) injected intraperitoneally.
      Immunohistochemical examination revealed that tyrosine hydroxylase (TH)-positive
      chromaffin cells could be identified adjacent to the spinal cord up to 4 weeks
      after i.t. implantation, whereas at 8 weeks the TH-positive cells were sparse. It
      is concluded that bovine chromaffin cells stay viable in rat spinal cord for a
      considerable period of time after i.t. administration and alleviate chronic
      allodynia-like behavior in spinally injured rats, possibly through activation of
      opioid and alpha-adrenoceptors. The present results further document a new
      therapeutic approach for the treatment of chronic neuropathic pain.

PMID- 9520226
TI  - Afferent activity from myelinated inferior alveolar nerve fibers in ferrets after
      constriction or section and regeneration.
AB  - To investigate possible peripheral mechanisms for post-injury sensory disorders
      in the trigeminal system, we have made electrophysiological recordings from
      myelinated fibres in the inferior alveolar nerve (IAN) which have previously
      sustained an injury. In earlier experiments we have shown that axons in ligature
      induced neuromas of the IAN develop spontaneous activity and mechanical
      sensitivity. The present study has investigated these responses after two
      different types of injury. In 24 anaesthetised adult male ferrets the left IAN
      was either chronically constricted by four loose chromic gut ligatures (12
      animals) or sectioned and regeneration permitted (12 animals). After recovery
      periods of 3 days, 1, 3, 6, 12 or 24 weeks, single unit recordings were made from
      the nerve proximal to the injury site. The proportion of units which were
      spontaneously active ranged from 0% to 19% after constriction injury and from 0%
      to 10% after nerve section and regeneration. Both groups revealed a marked
      variability between individual animals at similar time periods. Mechanical
      sensitivity was found in 0-42% of units after constriction and 0-25% of units
      after nerve section; both groups showed a significant negative correlation
      between mechanical sensitivity and recovery period. None of the fibres which had
      regained peripheral receptive fields was either spontaneously active or
      mechanically sensitive. There was no significant difference between the levels of
      spontaneous activity or mechanical sensitivity in the two groups or that
      previously found in ligature-induced neuromas. Thus we conclude that widely
      differing types of peripheral nerve injury are capable of initiating similar
      raised levels of afferent activity in myelinated inferior alveolar nerve fibres.

PMID- 9520227
TI  - Double-blind evaluation of short-term analgesic efficacy of orally administered
      diclofenac, diclofenac plus codeine, and diclofenac plus imipramine in chronic
      cancer pain.
AB  - A prospective double-blind randomized trial was conducted on 184 cancer patients
      with moderate to severe chronic pain to evaluate the analgesic efficacy and
      tolerability of diclofenac alone (50 mg q.i.d.) or in combination with a weak
      opioid (codeine 40 mg q.i.d.), or with an anti-depressant (imipramine, 10 or 25
      mg t.i.d.). All demographic and clinical characteristics including cancer type,
      presence of bone metastases, baseline pain severity, neuropathic and nociceptive
      pain, and depressive state, were well balanced between the three treatment
      groups. The main analysis of the study was on the VAS scores at visit 2 (day 4).
      The mean VAS values for both associations imipramine plus diclofenac and codeine
      plus diclofenac were similar to the association placebo plus diclofenac. Patients
      on imipramine plus diclofenac and on placebo plus diclofenac were withdrawn
      mainly for inadequate efficacy, while patients on codeine plus diclofenac
      discontinued equally for inadequate efficacy or adverse events. In conclusion, in
      a short-term evaluation the addition of a tricyclic anti-depressant or a weak
      opioid to diclofenac did not provide further analgesia with respect to diclofenac
      administration alone.

PMID- 9520228
TI  - Hyperalgesia in a human model of acute inflammatory pain: a methodological study.
AB  - The aim of the study was to examine reproducibility of primary and secondary
      hyperalgesia in a psychophysical model of human inflammatory pain. Mild burns
      were produced on the crura of 12 volunteers with a 50 x 25 mm thermode (47
      degrees C, 7 min). Assessments of (i) cold and warm detection thresholds, (ii)
      mechanical and heat pain thresholds, (iii) pain to heat (43 degrees C and 45
      degrees C, 5 s), (iv) secondary hyperalgesia, and (v) skin erythema were made
      1.75 and 0.5 h before, and 0, 1, 2, 4, and 6 h after a burn injury. Sensory
      thresholds and hyperalgesia to heat and mechanical stimuli were examined by
      contact thermodes and von Frey hairs, and pain intensity was rated with a visual
      analog scale (0-100). To describe between-day reproducibility, the subjects were
      examined three times at intervals of 21 days. Within-day comparisons showed that
      a 20% change could be detected as significant for all variables with fewer than
      12 subjects in a cross-over design (2alpha = 5% and power = 80%). Between-day
      comparisons demanded up to 25 subjects to detect changes of the same magnitude.
      The burns caused mild to moderate pain (VAS: mean 29, SD 14) and the subjects
      (all right-handed) were more sensitive to heat pain on their left side (P <
      0.03). Hyperalgesia was induced instantaneously by the burn and outlasted the
      study period (6 h). However, no spontaneous pain was observed after the injury,
      and a brief period of hypoesthesia to warm and cold stimuli was induced by the
      burn. The painful measurements themselves evoked hyperalgesia to heat and
      mechanical stimuli on the arm, but only to mechanical stimuli on the legs.
      including secondary hyperalgesia. Hyperalgesia evoked by the measurements was
      significantly less intense than that induced by injury. Habituation to the
      painful stimuli was demonstrated by significantly higher pain thresholds and
      lower pain responses on the second and third day of the study. The burn model is
      a sensitive psychophysical model of acute inflammatory pain, when cross-over
      designs and within-day comparisons are used, and the model is suitable for double
      blind, placebo-controlled studies of analgesics. In similar models, we recommend
      that analgesic and placebo are evenly divided between right and left sides and
      study days.

PMID- 9520229
TI  - Ambulatory accelerometry to quantify motor behaviour in patients after failed
      back surgery: a validation study.
AB  - In the treatment of patients with pain, measures related to (pain) behaviour are
      of major importance. Ambulatory activity monitoring can be used to obtain insight
      into actual behaviour. This study was designed to validate the Activity Monitor
      (AM), an instrument based on long-term ambulatory monitoring of accelerometer
      signals, to assess several physical activities during normal daily life. Ten
      failed back surgery (FBS) patients performed a number of functional activities in
      and around their own houses. During the measurements, continuous ambulatory
      registrations of accelerometer signals were made, based on four body-mounted
      accelerometers (one on each upper leg, two on the trunk). Video recordings made
      simultaneously with the measurements were used as a reference. The continuous
      output of the AM (postures, transitions, dynamic activities) was compared with
      visual analysis of the videotapes. The overall results showed an agreement
      between AM output and video analysis of 87% (inter subject range: 83-88%). The
      maximal error in the determination of the duration of activities was 0.3%. The
      overall number of dynamic periods was determined well (AM: 359; video: 368),
      while the number of transitions was slightly overestimated (AM: 228; video: 205).
      The results when using the three-sensor version of the AM were somewhat less
      accurate (overall agreement from 87% to 82%). The AM appeared to be a valid
      instrument to quantify aspects of behaviour of FPS patients, such as duration of
      activities and number of transitions. This new technique of ambulatory
      measurement of mobility activities seems to be a relevant and promising extension
      of the techniques currently used in the evaluation of pain treatment.

PMID- 9520230
TI  - Examiner expectancy effects in the measurement of pressure pain thresholds.
AB  - The ascending Method of Limits, used for the determination of pressure pain
      thresholds (PPT), is not a psychophysically robust method. The present study
      sought to determine if the examiner's expectancy, based on whether the
      measurement site was clinically 'painful' or 'non-painful', would bias the
      obtained PPT values. Twenty-eight patients with facial or temporal area pain
      served as subjects, and in each subject, a pain site and a control site were
      identified and marked. According to a randomization schedule, the pain and
      control sites were correctly marked in half of the subjects and were mis-labeled
      in the other half, thereby controlling the examiner's knowledge of a site and
      thus the examiner's expectancy of what the PPT should be. Two examiners, shown to
      be reliable with each other in both pre-clinical and post-clinical reliability
      studies, were blind to the true purpose of the study and to the marking
      procedures. Each examiner made one PPT measurement at each marked site in a
      counterbalanced measurement order. Manipulating the examiner's prior knowledge of
      the measurement site's characteristics significantly lowered the obtained PPT
      values for control sites but did not significantly alter the PPT at the
      clinically painful sites. Nevertheless, the pain sites still had significantly
      lower PPTs than did control sites. We conclude that: (i) PPTs at pain sites are
      robust to a major source of measurement bias associated with the ascending Method
      of Limits; (ii) measurement order and knowledge of measurement site
      characteristics can influence obtained PPT; and (iii) the common protocol in
      which the examiner monitors the amount of pressure during PPT measurement in
      order to control the force application rate may serve as a mechanism that can
      bias the obtained values.

PMID- 9520231
TI  - Pharmacological and neuroanatomical evidence for the involvement of the anterior
      pretectal nucleus in the antinociception induced by stimulation of the dorsal
      raphe nucleus in rats.
AB  - Several studies have shown that the anterior pretectal nucleus (APtN) is involved
      in descending inhibitory pathways that control noxious inputs to the spinal cord
      and that it may participate in the normal physiological response to noxious
      stimulation. Among other brain regions known to send inputs to the APtN, the
      dorsal column nuclei (DCN), pedunculopontine tegmental nucleus (PPTg), deep
      mesencephalon (DpMe), and dorsal raphe nucleus (DRN) are structures also known to
      be involved in antinociception. In the present study, the effects of stimulating
      these structures on the latency of the tail withdrawal reflex from noxious
      heating of the skin (tail flick test) were examined in rats in which saline or
      hyperbaric lidocaine (5%) was previously microinjected into the APtN. Brief
      stimulation of the PPTg, DpMe or DRN, but not the DCN, strongly depressed the
      tail flick reflex. The antinociceptive effect of stimulating the DRN, but not the
      PPTg or DpMe was significantly reduced, but not abolished, by the prior
      administration of the local anaesthetic into the APtN. The antinociception
      induced by stimulation of the PPTg or DpMe, therefore, is unlikely to depend on
      connections between these structures and the APtN. Similar inhibition of the
      effect of stimulating the DRN was obtained from rats previously microinjected
      with naloxone (2.7 nmol) or methysergide (2 nmol) into the APtN. Strongly
      labelled cells were identified in the DRN following microinjection of the
      fluorescent tracer Fast Blue into the APtN. These results indicate that the APtN
      may participate as a relay station through which the DRN partly modulates spinal
      nociceptive messages. In addition, they also indicate that endogenous opioid and
      serotonin can participate as neuromodulators of the DRN-APtN connection.

PMID- 9520233
TI  - Hyperalgesia and temporal summation of pain after heat injury in man.
AB  - Temporal summation of pain occurs when repeated stimuli become increasingly
      painful in spite of unchanged stimulus intensity. Summation can be quantified as
      the difference in pain between the first and the last stimulus in a train of
      stimuli. The aim of the study was to compare temporal summation of pain in normal
      skin with summation of pain in skin with primary and secondary hyperalgesia
      evoked by a heat injury. A heat injury was produced on the crus of 12 volunteers
      with a 50 x 25 mm thermode (47 degrees C, 7 min). Measurements were made before,
      and 0, 1, 2, and 4 h after the heat injury, in three areas: primary and secondary
      mechanical hyperalgesia induced by the heat injury, and in a mirror image of the
      injury on the opposite leg. Temporal summation of pain was induced by repeated
      electrical stimuli (five stimuli at 2 Hz) and assessed by visual analog scale
      (VAS). Primary hyperalgesia was evaluated by von Frey hairs and electrical
      stimuli, and the areas of secondary hyperalgesia with a rigid von Frey hair (314
      mN). Significant primary (P < 0.000001) and secondary (P < 0.00006) mechanical
      hyperalgesia were evoked by the heat injury. The pain threshold to single
      electrical stimuli was reduced within the injury (P < 0.03), but not outside. The
      pain responses to single and repeated electrical stimuli were not significantly
      altered by the injury. Temporal summation of pain occurred in 418 stimulus trains
      out of 576 (73%), but no significant changes in summation developed in skin with
      primary or secondary mechanical hyperalgesia compared with normal skin (baseline
      measurements). Temporal summation at high stimulus intensities was more
      pronounced than at lower intensities (P < 0.0002). We found no correlation
      between either temporal summation and area of secondary hyperalgesia, or temporal
      summation and pain intensity during the induction of heat injury. We conclude
      that the development of primary and secondary mechanical hyperalgesia after heat
      injury in man was not associated with changes in temporal summation of painful
      electrical stimuli.

PMID- 9520232
TI  - Sex differences in the perception of noxious experimental stimuli: a meta
      analysis.
AB  - Fillingim and Maixner (Fillingim, R.B. and Maixner, W., Pain Forum, 4(4) (1995)
      209-221) recently reviewed the body of literature examining possible sex
      differences in responses to experimentally induced noxious stimulation. Using a
      'box score' methodology, they concluded the literature supports sex differences
      in response to noxious stimuli, with females displaying greater sensitivity.
      However, Berkley (Berkley, K.J., Pain Forum, 4(4) (1995) 225-227) suggested the
      failure of a number of studies to reach statistical significance suggests the
      effect may be small and of little practical significance. This study used meta
      analytic methodology to provide quantitative evidence to address the question of
      the magnitude of these sex differences in response to experimentally induced
      pain. We found the effect size to range from large to moderate, depending on
      whether threshold or tolerance were measured and which method of stimulus
      administration was used. The values for pressure pain and electrical stimulation,
      for both threshold and tolerance measures, were the largest. For studies
      employing a threshold measure, the effect for thermal pain was smaller and more
      variable. The failures to reject the null hypothesis in a number of these studies
      appear to have been a function of lack of power from an insufficient number of
      subjects. Given the estimated effect size of 0.55 threshold or 0.57 for
      tolerance, 41 subjects per group are necessary to provide adequate power (0.70)
      to test for this difference. Of the 34 studies reviewed by Fillingim and Maixner,
      only seven were conducted with groups of this magnitude. The results of this
      study compels to caution authors to obtain adequate sample sizes and hope that
      this meta-analytic review can aid in the determination of sample size for future
      studies.

PMID- 9520234
TI  - Status of patients with chronic pain 13 years after treatment in a pain
      management center.
AB  - This study describes the current vital, health, and employment status of 249
      patients with chronic pain who were treated in a pain management center at the
      Mayo Clinic, on average, 13 years ago. These patients do not have an increased
      risk of mortality; their death rate is similar to that of the US white
      population. However, 68% of the patients reported worse-than-average or an
      abnormal level of bodily pain, with increased morbidity in their physical health,
      physical functioning, and social functioning. Emotional and mental health were
      claimed to be adequate. About half of the patients reported being gainfully
      employed.

PMID- 9520235
TI  - Dose-response relationship of opioids in nociceptive and neuropathic
      postoperative pain.
AB  - The treatment of neuropathic pain with opioid analgesics is a matter of
      controversy among clinicians and clinician scientists. Although neuropathic pain
      is usually believed to be only slightly responsive to opioids, several studies
      show that satisfactory analgesia can be obtained if adequate doses are
      administered. In the present study, we tested the effectiveness of buprenorphine
      in 21 patients soon after thoracic surgery (nociceptive postoperative pain) and 1
      month after surgery in the same 21 patients who developed postthoracotomy
      neuropathic pain with a burning, electrical and shooting quality. According to a
      double-blind randomized study, the analgesic dose (AD) of buprenorphine needed to
      reduce the long-term neuropathic pain by 50% (AD50) was calculated and compared
      to the AD50 in the immediate postoperative period. We found that long-term
      neuropathic pain could be adequately reduced by buprenorphine. However, the AD50
      in neuropathic pain was significantly higher relative to the AD50 in the short
      term postoperative pain, indicating a lower responsiveness of neuropathic pain to
      opioids. We also found a strict relationship between the short-term and long-term
      AD50, characterized by a saturating effect. In fact, if the AD50 soon after
      surgery was low, the AD50 increase in the long-term neuropathic pain was
      threefold. By contrast, if the AD50 soon after surgery was high, the AD50 in
      neuropathic pain was only slightly increased. This suggests that, though
      neuropathic pain is indeed less sensitive to opioids, in some neuropathic
      patients a large amount of opioid resistance is already present in other painful
      conditions.

PMID- 9520236
TI  - Intrathecal non-NMDA excitatory amino acid receptor antagonists inhibit pain
      behaviors in a rat model of postoperative pain.
AB  - Evidence indicates that excitatory amino acids (EAAs) like glutamate and
      aspartate are important in the processing of nociceptive information in the
      dorsal horn of the spinal cord. Recently, the role of particular EAA receptors in
      pain transmission and facilitated pain states has been examined utilizing spinal
      administration of specific receptor antagonists. Most investigators have studied
      the involvement of N-methyl-D-aspartate (NMDA) EAA receptors in hyperalgesia and
      nociception; less is known about the importance of non-NMDA EAA receptors in
      animal models of persistent pain. To study the role of spinal non-NMDA EAA
      receptors in pain behaviors caused by an incision, we examined the effect of i.t.
      administered non-NMDA EAA receptor antagonists in a rat model of postoperative
      pain. Rats with i.t. catheters were anesthetized and underwent a plantar
      incision. Withdrawal threshold to punctate stimulation applied adjacent to the
      wound using von Frey filaments, response frequency to application of a non
      punctate stimulus applied directly to the wound and non-evoked pain behaviors
      were measured before and after administration of i.t. 1,2,3,4-tetrahydro-6-nitro
      2,3-dioxo[f]quinoxaline-7-sulfonamide (NBQX), 6,7-dinitroquinoxaline-2,3-dione
      (DNQX), or vehicle. A separate group of animals were also tested for motor
      impairment caused by these drugs. In the vehicle-treated group, the median
      withdrawal threshold for punctate hyperalgesia decreased from 522 mN before
      surgery to 39 mN 2 h later; hyperalgesia was persistent. Intrathecal
      administration of 5 or 10 nmol of NBQX returned the withdrawal threshold toward
      preincision values; the median withdrawal thresholds were 158 and 360 mN,
      respectively. Intrathecal administration of 10 nmol of DNQX similarly increased
      the withdrawal threshold after incision. In separate groups of animals, i.t.
      administration of 5 or 10 nmol of NBQX decreased the response frequency to a non
      punctate stimulus applied directly to the incision from 100+/-0% 2 h after
      surgery to 22+/-11 and 0+/-0% 30 min after drug injection, respectively. Similar
      results were observed with i.t. administration of 10 nmol of DNQX. Intrathecal
      NBQX also inhibited non-evoked pain behavior. In conclusion, non-NMDA receptor
      antagonists produced a marked decrease in pain behaviors in this model of
      postoperative pain. Thus, non-NMDA receptors are important for the maintenance of
      short-term pain behaviors caused by an incision and drugs blocking these
      receptors may be useful for the treatment of postoperative pain in patients.

PMID- 9520237
TI  - Intraplantar injection of hyaluronic acid at low pH into the rat hindpaw produces
      tissue acidosis and enhances withdrawal responses to mechanical stimuli.
AB  - Application of buffers covering a range of acidic pH values activates and
      sensitizes nociceptors and produces pain. The purpose of this study was to
      determine whether a range of acidic pH in tissue produces mechanical
      hyperalgesia. Tissue acidosis was produced in the hindpaw of the rat by
      intraplantar injections of hyaluronic acid (HA) adjusted to pH 7.4, 6.0, 5.0, 4.0
      or 3.0. Mechanical hyperalgesia was assessed by evaluating responses to
      application of a von Frey monofilament to the plantar surface before and after
      injection of HA. In separate experiments, magnitude of tissue acidosis produced
      by injection of HA was determined by measuring pH of intraplantar tissue using a
      pH microelectrode. Although needle stick alone produced mechanical hyperalgesia,
      intraplantar injections of HA at pH 6.0 or 5.0 produced significantly greater
      mechanical hyperalgesia. In contrast, mechanical hyperalgesia produced by
      injection of HA at pH 7.4, 4.0 or 3.0 was not different from that produced by
      needle stick. Although injection of HA at low pH produced tissue acidosis in a pH
      dependent manner, only a narrow range of tissue acidosis (pH = 6.38-6.00)
      produced mechanical hyperalgesia. Our data suggest that tissue acidosis induces
      mechanical hyperalgesia; however, the range of tissue pH that produces this
      effect is limited.

PMID- 9520238
TI  - Antinociception by adenosine analogs and inhibitors of adenosine metabolism in an
      inflammatory thermal hyperalgesia model in the rat.
AB  - The present study examined the spinal antinociceptive effects of adenosine
      analogs and inhibitors of adenosine kinase and adenosine deaminase in the
      carrageenan-induced thermal hyperalgesia model in the rat. The possible
      enhancement of the antinociceptive effects of adenosine kinase inhibitors by an
      adenosine deaminase inhibitor also was investigated. Unilateral hindpaw
      inflammation was induced by an intraplantar injection of lambda carrageenan (2
      mg/100 microl), which consistently produced significant paw swelling and thermal
      hyperalgesia. Drugs were administered intrathecally, either by acute percutaneous
      lumbar puncture (individual agents and combinations) or via an intrathecal
      catheter surgically implanted 7-10 days prior to drug testing (antagonist
      experiments). N6-cyclohexyladenosine (CHA; adenosine A1 receptor agonist; 0.01-1
      nmol), 2-[p-(2-carboxyethyl)phenylethylamino]-5'-N-ethylcarboxamidoadenos ine
      (CGS21680; adenosine A2A receptor agonist; 0.1-10 nmol), 5'-amino-5'
      deoxyadenosine (NH2dAdo; adenosine kinase inhibitor: 10-300 nmol), and 5
      iodotubercidin (ITU; adenosine kinase inhibitor; 0.1-100 nmol) produced, to
      varying extents, dose-dependent antinociception. No analgesia was seen following
      injection of 2'-deoxycoformycin (dCF; an adenosine deaminase inhibitor; 100-300
      nmol). Reversal of drug effects by caffeine (non-selective adenosine A1/A2
      receptor antagonist; 515 nmol) confirmed the involvement of the adenosine
      receptor, while antagonism by 8-cyclopentyl-1,3-dimethylxanthine (CPT; adenosine
      A1 receptor antagonist; 242 nmol), but not 3,7-dimethyl-1-propargylxanthine
      (DMPX; adenosine A2A receptor antagonist; 242 nmol), evidenced an adenosine A1
      receptor mediated spinal antinociception by NH2dAdo. dCF (100 nmol), which was
      inactive by itself, enhanced the effects of 10 nmol and 30 nmol NH2dAdo.
      Enhancement of the antinociceptive effect of ITU by dCF was less pronounced. None
      of the antinociceptive drug regimens had any effect on paw swelling. These
      results demonstrate that both directly and indirectly acting adenosine agents,
      when administered spinally, produce antinociception through activation of spinal
      adenosine A1 receptors in an inflammatory model of thermal hyperalgesia. The
      spinal antinociceptive effects of selected adenosine kinase inhibitors can be
      significantly augmented when administered simultaneously with an adenosine
      deaminase inhibitor.

PMID- 9520239
TI  - Adaptation to metastatic cancer pain, regional/local cancer pain and non-cancer
      pain: role of psychological and behavioral factors.
AB  - The present study compared the adaptation of cancer pain patients and chronic non
      cancer pain patients. Differences between samples of cancer pain patients with
      and without metastatic disease were also examined. Cancer pain patients reported
      comparable levels of pain severity to non-cancer chronic pain patients; however,
      pain due to cancer was associated with higher levels of perceived disability
      (t(250) = 2.97, P < 0.004) and lower degree of activity (t(286) = 2.45, P <
      0.04). The patients with cancer pain, particularly those with metastatic disease,
      reported significantly higher levels of support and solicitous behaviors from
      significant others, compared to non-cancer chronic pain patients. The majority of
      the cancer patients, both with (81%) and without (84%) metastatic disease as well
      as non-cancer chronic pain patients (85%), could be classified into one of three
      psychosocial subgroups that had been previously identified with non-cancer
      chronic pain patients: 'dysfunctional' (high levels of pain, perceived
      interference, affective distress and low levels of perceived control and
      activity), 'interpersonally distressed' (high levels of affective distress,
      negative responses from significant others and low levels of perceived support)
      and 'adaptive copers' (low levels of interference and affective distress, high
      levels of perceived control and activity). The distribution of the profiles was
      significantly different across groups (chi2(4) = 12.79, P < 0.02). However,
      within each profile. the response patterns were highly comparable across groups.
      Thus, contrary to the suggestions of some authors, cancer pain and non-cancer
      chronic pain patients share many features in common. Furthermore, the
      heterogeneity of psychosocial adaptation to pain within each patient group
      suggests the importance of psychological assessment in determining the pain
      management plan.

PMID- 9520240
TI  - Secondary hyperalgesia and perceptual wind-up following intradermal injection of
      capsaicin in humans.
AB  - Wind-up and secondary hyperalgesia both are related to central sensitization, but
      whereas the former is explained by homosynaptic facilitation, the latter is due
      to heterosynaptic facilitation. To investigate possible interactions between both
      types of facilitation, we tested for alterations of perceptual wind-up in the
      secondary hyperalgesic skin zone adjacent to a capsaicin injection with light
      touch (by a cotton wisp) and punctate stimuli (calibrated von Frey hairs and pin
      pricks). Temporal summation of pain sensation (perceptual wind-up) was only
      observed with a clearly noxious stimulus (pin prick) presented at a repetition
      frequency of 0.6 s(-1), but not 0.2 s(-1). Pain ratings to trains of pin pricks
      reached a plateau after 3-4 repetitions, which was 1.65 times the initial rating
      ('wind-up ratio'). Injection of capsaicin induced a tenderness to mechanical
      stimuli in adjacent uninjured skin (secondary hyperalgesia), including
      hyperalgesia to light touch (allodynia) and hyperalgesia to punctate stimuli.
      Hyperalgesia to punctate stimuli was characterized by a leftward shift of the
      stimulus response function, corresponding to a decrease in pain threshold and an
      increase of painfulness of suprathreshold stimuli by a factor of 3-4. After
      capsaicin, the difference between the ratings of the first and last stimuli of
      trains of pin pricks was increased, but the ratio was unchanged. This behavior is
      equivalent to an increase in effective stimulus intensity, and could be mimicked
      by increasing the pin prick force from 20 mN to 40 and 80 mN in normal skin.
      Thus, the leftward shift of the stimulus response function fully accounts for all
      alterations of pain sensitivity to punctate stimuli in the zone of secondary
      hyperalgesia. We conclude that when the gain of spinal transmission was changed
      in secondary hyperalgesia, the gain of wind-up remained unchanged. These findings
      indicate that secondary hyperalgesia (heterotopic facilitation) and wind-up of
      pain sensation (homotopic facilitation) are independent phenomena.

PMID- 9520241
TI  - The enhancement of morphine antinociception by a CCKB receptor antagonist in the
      rat depends on the phase of inflammation and the intensity of carrageenin-induced
      hyperalgesia.
AB  - The ability of the cholecystokinin B (CCKB) receptor antagonist L-365,260 to
      modulate the antinociceptive action of systemic morphine was investigated using
      the well established rat model of localized inflammation induced by intraplantar
      injection of carrageenin. The effects of morphine (0.1-1 mg/kg i.v.) alone or in
      combination with the CCKB receptor antagonist (0.2 mg/kg s.c.) were determined at
      different time-points (at 1, 3 and 24 h) after the injection of carrageenin by
      measuring the vocalization threshold to paw pressure. L-365,260 was found to be
      ineffective in modulating the responses to all doses of morphine at 1 and 24 h
      after carrageenin. By contrast, at 3 h, the CCKB receptor antagonist reversed the
      ineffectiveness of the low dose (0.1 mg/kg i.v.) of morphine on the inflamed paw.
      Further, in the L-365,260-pretreated rats, a significant correlation between the
      antinociceptive effect of the low dose (0.1 mg/kg) of morphine and the intensity
      of the mechanical hyperalgesia was observed, indicating that the CCK control of
      the degree of sensitivity to opioids can vary among-the animals. Our data
      illustrate a differential and limited effect of L-365,260 on opioid
      antinociception in carrageenin-injected rats, depending on the dose of morphine,
      the phase of inflammation and the intensity of hyperalgesia.

PMID- 9520242
TI  - Psychophysical study of stinging pain evoked by brief freezing of superficial
      skin and ensuing short-lasting changes in sensations of cool and cold pain.
AB  - Psychophysical methods were used to investigate pain in human subjects elicited
      by controlled freezing of the skin using a novel vortex thermode. When cooling
      stimuli delivered with a small thermode (7 mm diameter) exceeded the normal cold
      pain threshold into the sub-zero temperature range (-5 to -11 degrees C), all
      subjects reported an intense, sharp stinging pain sensation which occurred
      suddenly and was readily differentiated from normal cold pain. The onset of this
      stinging 'freezing' pain was closely correlated with a sudden increase in skin
      temperature beneath the thermode of 4.77+/-0.86 degrees C (+/-SD) associated with
      the phase transition of supercooled water to ice. The mean intensity of freezing
      pain was rated as 1.7 times as intense as cold pain at threshold. Subjects' mean
      reaction-time latency to signal stinging pain following the onset of phase
      transition on the volar forearm was 687+/-220 ms, which was slower than that for
      mechanically evoked impact pain. Freezing pain is suggested to be mediated by A
      delta fibers, based on estimates of conduction velocity and on the observation
      that the freezing pain took on a burning quality of slower onset during an A
      fiber pressure block of nerve fibers. We also investigated changes in skin
      sensation following the freezing stimulus, and found that freezing led to (a) an
      immediate, significant decrease in the cold pain threshold (to higher
      temperatures), which recovered to baseline in < 16 min, (b) a concomitant change
      in the quality of cold pain from dull to burning, (c) a significant, parallel
      increase in the threshold for the perception of cooling (to lower temperatures)
      which frequently manifested as a complete loss of cold sensation, and (d) a mild
      heat pain hyperalgesia which was still present 24 h later. The changes in thermal
      sensitivity were not accompanied by consistent changes in mechanical sensitivity.
      These results indicate that a characteristic sharp, stinging pain is reliably
      evoked abruptly at the phase transition of supercooled skin water to ice The
      ensuing brief decrease in cold pain threshold with burning quality, coupled with
      decreased sensitivity to cold, are speculated to reflect a central disinhibition
      of C-fiber nociceptor input due to reduced cold fiber activity. These effects may
      be relevant to frostbite, and distinguish themselves from the more pronounced
      thermal and mechanical hyperalgesia seen following intense freeze lesion of the
      skin.

PMID- 9520243
TI  - Delayed antinociceptive effect following morphine-6-glucuronide administration in
      the rat--pharmacokinetic/pharmacodynamic modelling.
AB  - This study was conducted with the aim of characterising the pharmacokinetics and
      pharmacodynamics of morphine-6-glucuronide (M6G), a morphine metabolite
      possessing agonist properties. M6G was administered to three groups of rats as
      either a bolus dose, a 2 h computer-controlled stepwise infusion or as two
      consecutive 30-min infusions given 3 h apart. Clearance and initial volume of
      distribution were estimated to be 27 ml/min/kg for clearance and 339 ml/kg for
      initial volume. Morphine could not be detected until 4 h after dosing. The
      antinociceptive response profile, measured using the electrical stimulation
      vocalisation method, showed a pronounced delay in relation to the plasma
      concentration profile. The peak concentrations of 12,000 ng/ml, 6270 ng/ml and
      12,800 ng/ml in the bolus, the stepwise infusion and the two consecutive infusion
      groups gave corresponding maximal antinociceptive effects of 49%, 181% and 168%.
      A pharmacokinetic-pharmacodynamic model was applied to the data and the effect
      delay was estimated to be 1.4 h, which is considerably longer compared to
      morphine (0.5 h). Acute tolerance to the antinociceptive response was observed
      but could not be quantified due to the slowly ascending effect. Based on these
      results, the importance of study design for potency determination of drugs
      exhibiting different effect equilibration times was elucidated. Significant
      increases in the pCO2 levels were observed following the stepwise infusion and
      the two consecutive infusions. When compared to morphine, there was a tendency of
      a less pronounced effect on respiration by M6G.

PMID- 9520244
TI  - Randomized controlled trial of a community-based psychoeducation program for the
      self-management of chronic pain.
AB  - Although chronic pain is a frequent cause of suffering and disability and is
      costly to society, there continues to be limited access to specialty pain clinic
      services. Hence, there is a need for cost-effective, accessible interventions
      that will help people find ways to better manage this difficult problem. This
      randomized controlled trial examined the effect of a low-cost, community-based,
      nurse-delivered, group psychoeducation program entitled the Chronic Pain Self
      Management Program (CPSMP). It has a standard protocol that was modified from the
      successful Arthritis Self-Management Program (ASMP). One hundred and ten
      individuals with mixed idiopathic chronic pain conditions were enrolled in the
      study (75% female; mean age 40 years; mean chronicity 6 years) and were randomly
      assigned to one of two conditions: the 12-h (CPSMP) intervention group, or the 3
      month wait-list control group. Self-report measures of pain-related and other
      quality of life variables as well as two hypothesized mediating variables were
      collected pre-treatment and 3 months later by assessors blind to group
      allocation. One hundred and two subjects completed the study. Results of
      intention-to-treat analysis indicated that the treatment group made significant
      short-term improvements in pain, dependency, vitality, aspects of role
      functioning, life satisfaction and in self-efficacy and resourcefulness as
      compared to the wait-list control group. Because it has a standard protocol, this
      intervention has the potential to be reliably delivered at low cost in varied
      urban and rural community settings and hence be more widely accessible to a
      greater number of people suffering from chronic pain than is currently the case
      with more specialized pain clinic services. Based on the results of this study,
      further research evaluating the long-term impact and potential cost savings to
      the individual and to the health care system is warranted.

PMID- 9520246
TI  - Five-year outcomes in TMD: relationship of changes in pain to changes in physical
      and psychological variables.
AB  - Factors influencing natural history and clinical course of pain in
      temporomandibular disorders (TMD) are largely unknown. Physical, psychological
      and behavioral data from a population-based epidemiologic study of TMD were
      examined in 234 cases of persons reporting TMD pain. The cases were assigned to
      one of five pain pattern groups based on changes in average TMD pain from
      baseline to 5-year follow-up: (i) remitted (49% of the sample), (ii) high
      improvement (14%), (iii) low-improvement (9%), (iv) same (13%), and (v) worse
      (16%). For each pain change group, an ANOVA-derived pattern analysis was
      performed to assess whether the pattern of change in each of seven physical and
      three psychological variables was congruent or dissimilar to the pattern of
      change in average pain intensity. For none of the physical or psychological
      variables was the change over time completely congruent with the changes in pain.
      Changes in ambient average TMD pain were most closely related to those clinical
      variables whose assessment is influenced by pain or other self-reported symptoms
      (e.g., number of muscle sites painful to examiner palpation), while the amount of
      pain change was less closely related to changes in clinical variables, such as
      joint sounds, where assessment is not dependent on subjective report. The three
      psychological variables, anxiety, depression, and somatization, displayed similar
      change patterns, but these patterns were distinctly different from those of the
      physical variables in that the remitted pain group was at the population mean at
      baseline for these psychological variables and remained there; significant
      improvement in psychological status was observed only in the pain group showing
      high improvement. The other three pain change groups exhibited elevated
      psychological distress scores at both baseline and 5 years. These results
      indicate that although the relationships among the course of pain, of physical
      variables, and of psychological variables are complicated, the 5-year outcome in
      pain is largely independent of readily discernible changes in clinical signs.

PMID- 9520245
TI  - Spinal R-phenyl-isopropyl adenosine inhibits spinal dorsal horn neurons
      responding to noxious heat stimulation in the absence and presence of
      sensitization.
AB  - The effects of spinally administered R(-)N6-(2-phenylisopropyl) adenosine (R-PIA)
      on spinal dorsal horn neurons were investigated in anesthetized rats.
      Extracellular, single-unit recordings were measured during noxious heating of
      receptive fields on the hind paw. Three series of experiments were carried out to
      characterize the effects of R-PIA on spinal dorsal horn neuronal activity. In the
      first set of experiments, R-PIA dose-dependently suppressed noxiously evoked
      activity of spinal dorsal horn neurons. In the second set of experiments, R-PIA
      suppressed noxiously evoked activity in neurons sensitized by the topical
      application of mustard oil to a region of skin adjacent to their receptive
      fields. In the third set of experiments, R-PIA prevented mustard oil induced
      sensitization of dorsal horn neurons. In all cases, the adenosine receptor
      antagonist theophylline reversed the action of R-PIA. The results of these
      investigations indicate the involvement of spinal adenosine receptors in spinal
      pathways of central sensitization and in the modulation of somatically induced
      noxious pain.

PMID- 9520247
TI  - The role of prior pain experience and expectancy in psychologically and
      physically induced pain.
AB  - Cognitive theories regarding symptom formation suggest that environmental factors
      such as warnings of impending pain and earlier experiences with pain can lead to
      a cognitive schema in which pain is selectively monitored. This study evaluated
      the role of prior experience with pain in the development of expectancy induced
      somatoform pain. Subjects from two experimental groups were connected to a sham
      stimulator and told to expect a headache. One of these groups, the physical
      stimulation first group, was exposed to pain induction by ice water and by
      pressure prior to the sham stimulation. A second group, the sham stimulation
      first group, received the sham stimulation followed by the cold water and
      pressure pain induction techniques. Subjects in the physical stimulation first
      group showed significant increases in their pain reports as settings on the sham
      stimulator were increased. Significant increases were not noted in the sham
      stimulation first group. The two groups did not differ in the number of subjects
      reporting pain or the mean maximal pain reported during the sham stimulation.
      Duration of cold water tolerance and the time until the analgesic threshold level
      for cold water were significantly shorter in subjects who had the sham
      stimulation first. This study suggests that prior pain can influence the
      reactivity to external suggestion for pain but does not increase the frequency of
      pain reports. It does suggest that the selective monitoring induced during the
      sham stimulation may influence later pain behaviours as was seen during the cold
      water tolerance testing.

PMID- 9520248
TI  - Management of cardiac pacemaker in a patient with spinal cord stimulator implant.
AB  - Spinal cord stimulation reduces pain of critical ischaemia in patients with
      severe inoperable coronary artery and peripheral vascular disease by increasing
      microvascular flow. Patients with cardiac pacemaker may be denied a spinal cord
      stimulator (SCS) implant because of the risk of compromising pacemaker function
      by inhibition or reversion to asynchronous noise-pacing mode. We describe the
      management of a patient with an SCS implant for lower limb ischaemia who required
      a pacemaker. We suggest that with modern pacemakers it is safe to implant a
      spinal cord stimulator simultaneously with a pacemaker provided adequate
      precautions are taken to prevent interdevice interference.

PMID- 9520249
TI  - Can patients with chronic neuropathic pain be cured by acute administration of
      the NMDA receptor antagonist amantadine?
AB  - The treatment of neuropathic pain remains a challenge as it rarely leads to long
      term relief of symptoms. We report three patients with chronic neuropathic pain,
      in whom acute administration of the N-methyl-D-aspartate (NMDA) receptor
      antagonist amantadine resulted in complete resolution of symptoms, presumably due
      to termination the central 'wind-up' phenomenon.

PMID- 9520250
TI  - Gabapentin induced polyneuropathy.
AB  - Gabapentin is an effective option for the treatment of neuropathic pain syndromes
      because of its efficacy and favorable side-effect profile. A case is presented of
      a 58 year old man who developed a painful polyneuropathy while being treated with
      gabapentin.

PMID- 9520251
TI  - Discordance between malignant hyperthermia susceptibility and RYR1 mutation
      C1840T in two Scandinavian MH families exhibiting this mutation.
AB  - The ryanodine receptor 1 (RYR1) mutation C1840T has been reported to segregate
      with malignant hyperthermia (MH) susceptibility in several families. We have
      investigated several Scandinavian MH families with respect to five different RYR1
      mutations reported to cause predisposition to MH, and we here report on two of
      the families in which the C1840T mutation was detected. In these two families
      there was recombination between MH susceptibility and this mutation in one and
      three individuals, respectively. These findings may suggest that it is necessary
      to reconsider the specificity of the IVCT and the role of C1840T as a cause of MH
      susceptibility in some families exhibiting this mutation.

PMID- 9520252
TI  - Cardiovascular risk factors in people with different genotypes in the
      insertion/deletion (I/D) polymorphism at the locus for angiotensin I-converting
      enzyme (ACE).
AB  - The deletion (D) allele of an insertion/deletion (I/D) polymorphism at the locus
      for angiotensin I-converting enzyme (ACE) has been reported to be an independent
      risk factor for myocardial infarction (MI), particularly in people lacking
      traditional risk factors. Furthermore, a borderline association between Lp(a)
      lipoprotein level and the I/D polymorphism at the ACE locus was reported in one
      study. We have searched for possible "level gene" or "variability gene" effects
      of ACE genes on Lp(a) lipoprotein, total cholesterol (TC), high density
      lipoprotein (HDL) cholesterol (HDLC), low density lipoprotein (LDL) cholesterol
      (LDLC), triglycerides (TG), apolipoprotein B (apoB), apolipoprotein A-I (apoA-I),
      and body mass index (BMI). None of these variables differed significantly between
      genotypes in the I/D polymorphism in any of three population samples. A single
      population sample created by combining the three series, exhibited an
      insignificant trend towards individuals carrying the D-allele having a higher
      level of Lp(a) lipoprotein than those lacking it, and DD homozygotes had a
      significantly higher Lp(a) lipoprotein level than the combined group of ID/II
      individuals (p = 0.03). These results may indicate that the D-allele of the I/D
      polymorphism at the ACE locus could influence the level of Lp(a) lipoprotein.

PMID- 9520253
TI  - Genetic analysis of adult-onset cataract in a city-based ophthalmic hospital.
AB  - Adult-onset cataract (AOC) is a major ocular health problem and is the number one
      cause of blindness in the world. It is interesting to note that if the
      development of cataract is delayed by 10 years, the number of cataract surgeries
      needed would decrease by 45%. To prevent or delay cataract, the molecular
      pathological mechanisms underlying the lens change have to be understood, and
      this requires that the genes involved in such mechanisms should be identified.
      Hence, in this study we aim to identify AOC families which show a clear mendelian
      inheritance pattern, as only these families would be ideal for mapping the genes
      responsible. Over a period of 8 months, from September 1995-April 1996, 17
      families with two or more affected members were identified. Segregation analysis
      showed autosomal dominant inheritance in multiple affected families. We propose
      to map the genes responsible for cataract in these families by linkage analysis
      and mutational screening of candidate genes.

PMID- 9520254
TI  - Mosaicism for a small supernumerary ring X chromosome in a dysmorphic, growth
      retarded male: mos47,XXY/48,XXY, +r(X).
AB  - Supernumerary ring X [r(X)] chromosomes are often found in patients with Turner
      syndrome. The phenotypic effects of the r(X) chromosome are variable, and largely
      depend on the presence or absence of the X inactivation (XIST) locus. Ring(X)
      chromosomes in males are rare and have been previously reported in only four
      cases, with 47,XY, + r(X) or mos47,XY, +r(X)/46,XY karyotypes. These patients all
      had developmental delay and dysmorphic features. We describe a 2.5-year-old male
      patient with facial dysmorphia, growth retardation, microcephaly, global
      developmental delay, and microphallus. Cytogenetic analysis from peripheral blood
      lymphocytes and fibroblasts identified mosaicism for two cell lines: mos48,XXY, +
      r(?X)/47,XXY. Fluorescence in situ hybridization (FISH) with an X chromosome
      paint showed the ring chromosome to be X chromosome derived. This is the first
      case of an r(X) chromosome described in a 47,XXY patient. FISH analysis of the
      r(X) chromosome with an XIST probe showed that the XIST locus was absent.
      Functional disomy of genes in the r(X) chromosome most likely accounts for the
      abnormal phenotype in the proband.

PMID- 9520255
TI  - Greig cephalopolysyndactyly syndrome: altered phenotype of a microdeletion
      syndrome due to the presence of a cytogenetic abnormality.
AB  - A male had several features of Greig cephalopolysyndactyly syndrome (GCPS) and
      significant developmental delay. He was found to have a de novo chromosomal
      deletion of chromosome no. 7 involving p13; this resulted in loss of the zinc
      finger gene, GLI3, which is the candidate gene in this syndrome. Modification of
      the CGPS phenotype in a sporadic case emphasizes the importance of searching for
      a chromosomal origin of this autosomal dominant disorder. Detection of a
      chromosomal deletion in these patients may be associated with a poor prognosis
      from the standpoint of cognitive development, and the potential for other
      structural abnormalities not normally associated with GCPS.

PMID- 9520256
TI  - Partial trisomy of 15q due to inserted inverted duplication.
AB  - A de novo abnormal chromosome 15, with an inverted duplication of the segment
      (15q13.3 --> 15q21.3) at 15q24.3, was found in a boy with mild developmental
      delay, facial dysmorphism, Marfan-like appearance and severe language delay.
      There is an unusual disparity between the severe lack of speech and the presence
      of reasonable skills in other areas.

PMID- 9520257
TI  - Variant euchromatic band within 16q12.1.
AB  - The enlarged short arm of chromosome 16 resulting in an additional euchromatic
      band has been regarded as a variant. We present an unreported case with an
      unusual variant of chromosome 16, where the mother and daughter both have an
      additional band (q12.1) in the long arm. Its origin is chromosome 16, as revealed
      by FISH-technique, and its familial nature suggests that it has no clinical
      significance.

PMID- 9520258
TI  - Control of effective expression of the phage phiCTX-encoded ctx gene in
      Pseudomonas aeruginosa by a promoter upstream of the cos site.
AB  - In the DNA of bacteriophage phiCTX, the attachment site (attP), the cohesive end
      site (cos), and the gene (ctx) encoding the pore-forming cytotoxin, are
      clustered. Deletion variants and PCR-generated fragments of the DNA were cloned
      into the Pseudomonas aeruginosa and Escherichia coli vector pHA10. Recombinant
      plasmids carrying the chloramphenicol acetyltransferase gene, cat, were used for
      promoter studies. Two promoters responsible for ctx expression are located
      between attP and cos and between cos and ctx, the promoter upstream of cos being
      stronger than the one downstream. The promoters and the ribosomal binding site
      are recognized by both the P. aeruginosa and E. coli transcriptional systems. The
      results indicate that chromosomal integration of phiCTX DNA, which requires cos
      site ligation, is necessary for high ctx expression in phiCTX-infected P.
      aeruginosa strains.

PMID- 9520259
TI  - The Aspergillus nidulans sulphur regulatory gene sconB encodes a protein with
      WD40 repeats and an F-box.
AB  - The Aspergillus nidulans gene sconB, one of the four identified genes controlling
      sulphur metabolite repression, was cloned and analysed. It encodes a polypeptide
      of 678 amino acids containing seven WD repeats characteristic of the large WD40
      family of eukaryotic regulatory proteins. The SCONB protein has nuclear
      localisation signals and is very similar to the Neurospora crassa SCON2 and
      Saccharomyces cerevisiae Met30 proteins, both of which are involved in the
      regulation of sulphur metabolism. The N. crassa scon-2 gene complements the
      sconB2 mutation. All three proteins also contain a newly identified motif, the F
      box, found in a number of eukaryotic regulatory proteins. This motif is
      responsible, at least in some cases, for ubiquitin-mediated proteolysis. The
      sconB transcript is derepressed under sulphur limitation conditions and partly
      repressed by high methionine.

PMID- 9520260
TI  - The P25 component of Galleria silk.
AB  - The water-insoluble core of lepidopteran silk is composed of four major proteins,
      but only three genes have been identified. This study demonstrates that the 29-
      and 30-kDa components of Galleria mellonella silk are derived from a single gene
      designated P25. The gene is expressed exclusively in the posterior section of the
      silk glands as a 2-kb mRNA, which accumulates in the feeding larvae and declines
      at molting. The mRNA encodes a peptide of 24,864 Da that exhibits 51% identity
      with the putative product of the P25 gene of Bombyx. The conservation of several
      amino acid stretches, including the relative positions of all 8 cysteines in the
      mature polypeptide, implies that the P25 proteins play similar, and apparently
      significant roles in silk formation in the two species. A Galleria P25 cDNA
      yields a peptide of about 25 kDa when translated in vitro; the 29- and 30-kDa
      forms present in the silk are derived from this primary translation product by
      differential glycosylation.

PMID- 9520261
TI  - Shine-Dalgarno-like sequences are not required for translation of chloroplast
      mRNAs in Chlamydomonas reinhardtii chloroplasts or in Escherichia coli.
AB  - Initiation of translation in Escherichia coli and related eubacteria involves
      well-defined interactions between a conserved Shine-Dalgarno (SD) sequence
      immediately upstream of the initiation codon in the mRNA leader and an equally
      conserved anti-SD sequence at the 3' end of the 16S rRNA. SD-like sequences found
      in the leaders of many, but not all, mRNAs from cyanobacteria and chloroplasts
      are hypervariable in location, size, and base composition compared to those in E.
      coli, while anti-SD sequences in the respective 16S rRNAs remain highly
      conserved. We have examined the function of the SD-like sequences found in the
      leaders of four chloroplast genes of the green alga Chlamydomonas reinhardtii
      using replacement mutagenesis to eliminate complementarity with the anti-SD
      sequences and insertion of canonical SD sequences (GGAGG) at positions -9 to -5
      relative to the initiation codon. Promoter-leader regions of the atpB, atpE,
      rps4, and rps7 genes representing the diversity of chloroplast SD-like sequences
      were fused to aadA and uidA reporter genes encoding spectinomycin resistance and
      GUS activity respectively. Analysis of chloroplast transformants of C.
      reinhardtii and transformants of E. coli carrying the wild-type and mutant
      reporter constructs revealed that mutagenic replacement of the putative SD
      sequences had no effect on the expression of either the aadA or uidA reporter
      genes. Chloroplast transformants with the canonical SD sequence also showed no
      differences in reporter gene expression, whereas expression of the reporter genes
      was increased by 10 to 30% in the E. coli transformants. Collectively our results
      suggest that even though SD-dependent initiation predominates in E. coli, this
      bacterium also has the capacity to initiate translation by an SD-independent
      mechanism. In contrast, plant chloroplasts, and very probably their
      cyanobacterial ancestors, appear to have adopted the SD-independent mechanism for
      translational initiation of most mRNAs.

PMID- 9520262
TI  - Isolation and characterisation of the RAD51 and DMC1 homologs from Arabidopsis
      thaliana.
AB  - By using RT-PCR and degenerate oligonucleotides based on the sequence homology
      between the yeast RAD51 and DMC1 genes, two genes belonging to the RAD51 and DMC1
      families were isolated from Arabidopsis thaliana ecotype Columbia. A RAD51
      genomic DNA was also sequenced which is almost identical to its Landsberg erecta
      counterpart, except for a few translationally silent substitutions and for the
      presence of a 527-bp element downstream of the polyadenylation site. This element
      is repeated in the genome of Arabidopsis. Northern analyses were conducted to
      characterize the expression pattern of both these genes. AtRAD51 and AtDMC1 are
      expressed in flower buds, but also in the mitotically active cells from a
      suspension culture. AtRAD51, but not AtDMC1, transcript level increases after
      gamma irradiation of the cells. Finally, a synchronisation experiment conducted
      with the suspension culture indicated that not only AtRAD51 but also AtDMC1 are
      regulated during the cell cycle, with S-phase-specific induction. Since DMC1
      genes have always been regarded as being specifically meiotic, we discuss the
      significance of this mitotic transcriptional regulation in Arabidopsis.

PMID- 9520263
TI  - DNase-hypersensitive sites in yeast artificial chromosomes containing human DNA.
AB  - We have mapped the DNase I-hypersensitive sites (HSs) in Yeast Artificial
      Chromosomes (YACs) containing segments of human chromosomal DNA. One of the five
      HSs found in a YAC carrying the beta-globin gene cluster has been localised in
      the region, termed HS2, that is DNase I hypersensitive in most human cells. We
      have also identified a class of HSs in YACs containing DNA from the q11.2 band of
      human chromosome 21, which are located close to, or within, segments of the
      chromosome that are sensitive to restriction enzymes recognizing CGCG
      tetranucleotides.

PMID- 9520264
TI  - Transcript analysis of the tobacco plastid operon rps2/atpI/H/F/A reveals the
      existence of a non-consensus type II (NCII) promoter upstream of the atpI coding
      sequence.
AB  - The plastid ATP synthase complex is composed of nine subunits, of which six are
      encoded in the plastome. The plastid-encoded genes are arranged in two
      transcriptional units: atpB/E and atpI/H/F/A. We have recently reported that
      besides containing four -10 and -35 consensus-type (CT) promoters, the atpB/E
      operon also contains a non-consensus type (NCII) promoter that alone is
      responsible for its expression in non-photosynthetic plastids. As the
      functionality of ATP synthase requires expression of all nine subunits, NCII
      promoter-driven transcription of the atpI/H/F/A operon is to be expected in non
      photosynthetic plastids. Therefore, a detailed transcriptional analysis of this
      operon was carried out using RNA samples from tobacco leaf, cultured cells (BY-2)
      and seedlings grown on streptomycin and spectinomycin; which contain
      chloroplasts, translationally active non-photosynthetic plastids and
      translationally inactive plastids, respectively. We identified a total of three
      transcription initiation sites (TIS) and four transcript processing sites in the
      non-coding regions of this operon. Our results also demonstrate that rps2 is co
      transcribed with the atpI/H/F/A genes. One of the TIS (-208 atpI) is
      characterized by an NCII type promoter, while other two primary transcripts (-131
      atpI and -384 atpH) initiate from CT promoters. In non-photosynthetic plastids
      the atpI/H/F/A-specific transcript pool seems to be solely contributed by
      initiation at the -208 atpI (NCII type) promoter, because transcripts from CT
      promoters do not accumulate in these plastid types.

PMID- 9520265
TI  - Targeted alteration of the substrate specificity of peptide synthetases by
      rational module swapping.
AB  - Analysis of the primary structure of peptide synthetases involved in the non
      ribosomal synthesis of peptide antibiotics has revealed a highly conserved and
      ordered modular arrangement. A module contains at least two domains, involved in
      ATP-dependent substrate activation and thioester formation. The occurrence and
      arrangement of these functional building blocks is associated with the number and
      order of the amino acids incorporated in the peptide product. In this study, we
      present data on the targeted exchange of the leucine-activating module within the
      three-module surfactin synthetase 1 (SrfA-A) of Bacillus subtilis. This was
      achieved by engineering several hybrid srfA-A genes, which were introduced into
      the surfactin biosynthesis operon by in vivo recombination. We examined the
      hybrid genes for expression and investigated the enzymatic activities of the
      resulting recombinant peptide synthetases. For the first time, we demonstrate
      directly that an individual minimal module, of bacterial or fungal origin,
      confers its amino acid-specific activity on a multi-modular peptide synthetase.
      Furthermore, it is shown that directed incorporation of ornithine at the second
      position of the peptide chain induces a global alteration in the conformation of
      surfactin and may result in premature cyclization or a branched cyclic structure.

PMID- 9520266
TI  - Isolation and characterization of hrp1+, a new member of the SNF2/SWI2 gene
      family from the fission yeast Schizosaccharomyces pombe.
AB  - The SNF2/SWI2 ATPase/helicase family comprises proteins from a variety of
      species, which serve a number of functions, such as transcriptional regulation,
      maintenance of chromosome stability during mitosis, and various types of DNA
      repair. Several proteins with unknown functions are also included in this family.
      The number of genes that belong to this family is rapidly expanding, which makes
      it easier to analyze the common biological functions of the family members. This
      study was designed to clone the SNF2/SWI2 helicase-related genes from the fission
      yeast Schizosaccharomyces pombe in the hope that this would help to elucidate the
      common functions of the proteins in this family. The hrp1+ (helicase-related gene
      from S. pombe) gene was initially cloned by PCR amplification using degenerate
      primers based on conserved SNF2 motifs within the ERCC6 gene, which encodes a
      protein involved in DNA excision repair. The hrp1+ ORF codes for an 1373-amino
      acid polypeptide with a molecular mass of 159 kDa. Like other SNF2/SWI2 family
      proteins, the deduced amino acid sequence of Hrp1 contains DNA-dependent ATPase/7
      helicase domains, as well as a chromodomain and a DNA-binding domain. This
      configuration is similar to that of mCHD1 (mouse chromo-ATPase/helicase-DNA
      binding protein 1), suggesting that Hrp1 is a S. pombe homolog of mCHD1, which is
      thought to function in altering the chromatin structure to facilitate gene
      expression. Northern blot analysis showed that the hrp1+ gene produces a 4.6-kb
      transcript, which reaches its maximal level just before the cells enter the
      exponential growth phase, and then decreases gradually. DNA-damaging agents, such
      as MMS, MNNG and UV, decrease the rate of transcription of hrp1+. Deletion of the
      hrp1+ gene resulted in accelerated cell growth. On the other hand, overexpression
      of Hrp1 caused a reduction in growth rate. These results indicate that hrp1+ may
      act as a negative regulator of cellular growth.

PMID- 9520267
TI  - The Acinetobacter calcoaceticus NCIB8250 mop operon mRNA is differentially
      degraded, resulting in a higher level of the 3' CatA-encoding segment than of the
      5' phenolhydroxylase-encoding portion.
AB  - The 7.5-kb polycistronic mop mRNA is differentially degraded in Acinetobacter
      calcoaceticus. The 4.9-kb 5' portion of the transcript contains the genes
      mopKLMNOP, encoding the multi-component phenol hydroxylase, and its 5' end decays
      three times faster than the 2.3-kb 3' portion encoding catechol 1,2-dioxygenase
      (catA). Larger amounts of the catA mRNA than the mopKLMNOP mRNA are present in
      the cells as a result of this processing. The site for endonucleolytic cleavage
      is located in the intercistronic region between mopP and catA, and contains a
      potential stem-loop structure and a putative RNase E cleavage site. Decay of the
      mop mRNA in Escherichia coli depends on RNase E. Thus, we propose that an RNase E
      like activity is also present in A. calcoaceticus. Expression of MopN, one
      polypeptide of the multi-component phenol hydroxylase, interferes with growth of
      A. calcoaceticus. Thus, harmful expression of MopN may be reduced by rapid decay
      of its mRNA, indicating that mRNA processing contributes to differential gene
      expression in the large mop operon of A. calcoaceticus NCIB8250.

PMID- 9520268
TI  - Sequence analysis of glutamate dehydrogenase (GDH) from the hyperthermophilic
      archaeon Pyrococcus sp. KOD1 and comparison of the enzymatic characteristics of
      native and recombinant GDHs.
AB  - The gdhA gene encoding glutamate dehydrogenase (GDH) from the hyperthermophilic
      archaeon Pyrococcus sp. KOD1 was cloned and sequenced. Phylogenetic analysis was
      performed on an alignment of 25 GDH sequences including KOD1-GDH, and two protein
      families were distinguished, as previously reported. KOD1-GDH was classified as
      new member of the hexameric GDH Family II. The gdhA gene was expressed in
      Escherichia coli, and recombinant KOD1-GDH was purified. Its enzymatic
      characteristics were compared with those of the native KOD1-GDH. Both enzymes had
      a molecular mass of 47,300 Da and were shown to be functional in a hexameric form
      (284 kDa). The N-terminal amino acid sequences of native KOD1-GDH and the
      recombinant GDH were VEIDPFEMAV and MVEIDPFEMA, respectively, indicating that
      native KOD1-GDH does not retain the initial methionine at the N-terminus. The
      recombinant GDH displayed enzyme characteristics similar to those of the native
      GDH, except for a lower level of thermostability, with a half-life of 2 h at 100
      degrees C, compared to 4 h for the native enzyme purified from KOD1. Kinetic
      studies suggested that the reaction is biased towards glutamate production. KOD1
      GDH utilized both coenzymes NADH and NADPH, as do most eukaryal GDHs.

PMID- 9520269
TI  - Male sterility associated with APRT deficiency in Arabidopsis thaliana results
      from a mutation in the gene APT1.
AB  - Four mutants of Arabidopsis thaliana that are deficient in adenine phosphoribosyl
      transferase (APRT) activity have been isolated by selecting for germination of
      seeds and growth of the plantlets on a medium containing 2,6-diaminopurine (DAP),
      a toxic analog of adenine. In all mutants, DAP resistance is due to a recessive
      nuclear mutation at a locus designated apt. The mutants are male sterile due to
      pollen abortion after meiosis. Furthermore, it has been shown that metabolism of
      cytokinins is impaired in the mutant BM3, which has the lowest level of APRT
      activity among the mutants tested. However, three different cDNAs encoding APRT
      have been isolated in A. thaliana and this raised the question of the nature of
      the mutation which results in low APRT activity. The mutation was genetically
      mapped to chromosome I and lies within 6 cM of the phenotypic marker dis2,
      indicating that the mutation affects the APT1 gene, a result confirmed by
      sequencing of mutant alleles. The mutation in the allele apt1-3 is located at the
      5' splicing site of the third intron, and eliminates a BstNI restriction site, as
      verified by Southern blotting and PCR fragment length analysis.

PMID- 9520270
TI  - Characterization of novel proteins affected by the o2 mutation and expressed
      during maize endosperm development.
AB  - The effect of the o2 mutation on protein expression during grain development was
      examined by two-dimensional electrophoresis (2-D PAGE) in seven different pairs
      of near-isogenic maize lines. The aim was to identify a set of proteins that are
      consistently affected in mutants, and which could be the products of new genes
      that are direct or indirect targets of the transcriptional activator O2. The
      abundance of 36 polypeptides was found to be modified in the seven backgrounds.
      Seventeen polypeptides were present in greater amounts in wild types than in
      mutants, and most of these were affected early. The remaining polypeptides were
      expressed at higher levels in mutants than in the wild types and were generally
      affected later in development, suggesting that they might be products of indirect
      targets of O2. Products of known direct target genes such as zeins, b-32 protein
      and a pyruvate orthophospate dikinase were included in the first set of
      polypeptides. Microsequencing of internal stretches of 15 amino acids was
      performed for thirteen polypeptides and homologies with sequences stored in
      databases were found for nine of them. Enzymes belonging to various metabolic
      pathways were tentatively identified, most of which were not previously known to
      be affected by the o2 mutation. These results confirm that the O2 gene could act
      as a connecting regulatory gene for different pathways of grain metabolism.

PMID- 9520271
TI  - Analysis of in vivo correction of defined mismatches in the DNA mismatch repair
      mutants msh2, msh3 and msh6 of Saccharomyces cerevisiae.
AB  - We have analysed the correction of defined mismatches in wild-type and msh2,
      msh3, msh6 and msh3 msh6 mutants of Saccharomyces cerevisiae in two different
      yeast strain backgrounds by transformation with plasmid heteroduplex DNA
      constructs. Ten different base/base mismatches, two single-nucleotide loops and a
      38-nucleotide loop were tested. Repair of all types of mismatches was severely
      impaired in msh2 and msh3 msh6 mutants. In msh6 mutants, repair efficiency of
      most base/base mismatches was reduced to a similar extent as in msh3 msh6 double
      mutants. G/T and A/C mismatches, however, displayed residual repair in msh6
      mutants in one strain background, implying a role for Msh3p in recognition of
      base/base mismatches. Furthermore, the efficiency of repair of base/base
      mismatches was considerably reduced in msh3 mutants in one strain background,
      indicating a requirement for MSH3 for fully efficient mismatch correction. Also
      the efficiency of repair of the 38-nucleotide loop was reduced in msh3 mutants,
      and to a lesser extent in msh6 mutants. The single-nucleotide loop with an
      unpaired A was less efficiently repaired in msh3 mutants and that with an
      unpaired T was less efficiently corrected in msh6 mutants, indicating non
      redundant functions for the two proteins in the recognition of single-nucleotide
      loops.

PMID- 9520272
TI  - Inactivation of the gene coding for the 30.4-kDa subunit of respiratory chain
      NADH dehydrogenase: is the enzyme essential for Neurospora?
AB  - We have isolated and characterised the nuclear gene that codes for the 30.4-kDa
      subunit of the peripheral arm of complex I from Neurospora crassa. The single
      copy gene was localised on chromosome VI of the fungal genome by restriction
      fragment length polymorphism mapping. An extra copy of the gene was introduced
      into a strain of N. crassa by transformation. This strain was crossed with
      another strain in order to inactivate, by repeat-induced point mutations, both
      copies of the duplication carried by the parental transformant. Ascospore progeny
      from the cross were analysed and a mutant strain lacking the 30.4-kDa protein,
      nuo30.4, was isolated and further characterised. The mutant appears to assemble
      the membrane arm of complex I, while formation of the peripheral arm is
      prevented. Nevertheless, the mutant grows reasonably well--indicating that this
      well conserved protein is not essential for vegetative growth--and is able to
      mate with other strains both as male or female. Strains with multiple mutations
      are readily obtained from heterozygous crosses between different complex I
      mutants of N. crassa. On the other hand, homozygous crosses between several
      mutants, including nuo30.4, fail to produce ascospores. These results suggest
      that complex I plays an essential role during the sexual phase of the life cycle
      of the fungus.

PMID- 9520273
TI  - Genetic and physical localization of the root-knot nematode resistance locus mi
      in tomato.
AB  - As part of a map-based cloning strategy designed to isolate the root-knot
      nematode resistance gene Mi, tomato F2 populations were analyzed in order to
      identify recombination points close to this economically important gene. A total
      of 21,089 F2 progeny plants were screened using morphological markers. An
      additional 1887 F2 were screened using PCR-based flanking markers. Fine-structure
      mapping of recombinants with newly developed AFLP markers, and RFLP markers
      derived from physically mapped cosmid subclones, localized Mi to a genomic region
      of about 550 kb. The low frequency of recombinants indicated that recombination
      was generally suppressed in these crosses and that crossovers were restricted to
      particular regions. To circumvent this problem, a population of Lycopersicon
      peruvianum, the species from which Mi was originally introgressed, that was
      segregating for resistance was developed. Screening of this population with PCR,
      RFLP and AFLP markers identified several plants with crossovers near Mi.
      Recombination frequency was approximately eight-fold higher in the Mi region of
      the L. peruvianum cross. However, even within the wild species cross,
      recombination sites were not uniformly distributed in the region. By combining
      data from the L. esculentum and L. peruvianum recombinant analyses, it was
      possible to localize Mi to a region of the genome spanning less than 65 kb.

PMID- 9520274
TI  - AIR synthetase in cowpea nodules: a single gene product targeted to two
      organelles?
AB  - A cDNA (VUpur5) encoding phosphoribosyl aminoimidazole (AIR) synthetase, the
      fifth enzyme of the de novo purine biosynthesis pathway has been isolated from a
      cowpea nodule cDNA library. It encodes a 388 amino acid protein with a predicted
      molecular mass of 40.4 kDa. The deduced amino acid sequence has significant
      homology with AIR synthetase from other organisms. AIR synthetase is present in
      both mitochondria and plastids of cowpea nodules. A signal sequence encoded by
      the VUpur5 cDNA has properties associated with plastid transit sequences but
      there is no consensus cleavage site as would be expected for a plastid targeted
      protein. Although the signal sequence does not have the structural features of a
      mitochondrial targeted protein, it has a mitochondrial cleavage site motif
      (RX/XS) close to the predicted N-terminus of the mature protein. Southern
      analysis suggests that AIR synthetase is encoded by a single gene raising
      questions as to how the product of this gene is targeted to the two organelles.
      VUpur5 is expressed at much higher levels in nodules compared to other cowpea
      tissues and the gene is active before nitrogen fixation begins. These results
      suggest that products of nitrogen fixation do not play a role in the initial
      induction of gene expression. VUpur5 was expressed in Escherichia coli and the
      recombinant protein used to raise antibodies. These antibodies recognize two
      forms of AIR synthetase which differ in molecular size. Both forms are present in
      mitochondria, although the larger protein is more abundant. Only the smaller
      protein was detected in plastids.

PMID- 9520275
TI  - The genomic organization of non-LTR retrotransposons (LINEs) from three Beta
      species and five other angiosperms.
AB  - We have isolated and characterized conserved regions of the reverse transcriptase
      gene from non-LTR retrotransposons, also called long interspersed nuclear
      elements (LINEs), from Beta vulgaris, B. lomatogona and B. nana. The novel
      elements show strong homology to other non-LTR retrotransposons from plants, man
      and animals. LINEs are present in all species of the genus Beta tested, but there
      was variation in copy number. Analysis by Southern hybridization and fluorescent
      in situ hybridization revealed the clustered organization of these retroelements
      in beet species. PCR amplification using degenerate primers to conserved motifs
      of the predicted LINE protein sequence enabled the cloning of LINEs from both
      Monocotyledonae (Allium cepa, Oryza sativa and Secale cereale) and Dicotyledonae
      (Nicotiana tabacum and Antirrhinum majus) indicating that LINEs are a universal
      feature of plant genomes. A dendrogram of fifteen new and six previously isolated
      sequences showed the high level of sequence divergence while revealing families
      characteristic of some genera. The genomic organization of non-LTR
      retrotransposons was examined more detailed in A. majus and O. sativa.

PMID- 9520276
TI  - The expression of a grapefruit gene encoding an isoflavone reductase-like protein
      is induced in response to UV irradiation.
AB  - Exposure of harvested grapefruit to UV-C (254 nm) irradiation was previously
      found to induce resistance against the green mold decay caused by Penicillium
      digitatum. In order to gain insight into the mechanism of this UV-induced
      resistance we initiated a study for isolation of genes induced during this
      process. Using the differential display method we cloned cDNA representing an
      mRNA which is accumulated in grapefruit peel upon UV irradiation. Sequence
      analysis revealed that this cDNA represents a gene encoding for an isoflavone
      reductase-like protein and was termed IRL (isoflavone reductase-like). The
      grapefruit IRL protein sequence has high homology also to a novel family of other
      isoflavone reductase-like proteins present in few non-legume plants and whose
      function is not clear yet. The UV dose, and time following it, which lead to
      maximal accumulation of the IRL transcript were found to be similar to those
      leading to maximal induced resistance. The expression of the IRL gene was
      demonstrated to be induced also by wounding and pathogen infection.

PMID- 9520277
TI  - Sucrose-phosphate synthase steady-state mRNA increases in ripening kiwifruit.
AB  - Early during fruit ripening in kiwifruit (Actinidia deliciosa var. deliciosa [A.
      Chev.], C.F. Liang and A.R. Ferguson cv. Hayward), starch is broken down to
      sucrose and hexose sugars. Concomitantly, sucrose-phosphate synthase (SPS, EC
      2.3.1.14) activity measured with saturating substrate increased, suggesting that
      SPS is induced in response to a higher requirement for sucrose synthesis. A 2584
      bp long partial cDNA clone encoding SPS was isolated from ripening kiwifruit.
      cDNA fragments encoding the 5' end were isolated by PCR, and sequencing revealed
      at least four closely related (> 96% identity) mRNAs expressed early in kiwifruit
      ripening. Southern hybridisations in a diploid relative of kiwifruit, Actinidia
      chinensis (Planch.) var. chinensis, were consistent with the presence of a small
      gene family. Western analysis indicated a 125 kDa SPS protein present in all
      tissues of A. chitensis at all stages of development. Steady-state levels of SPS
      mRNA in A. chinensis increased near fruit maturity as net starch degradation
      began on the vine, and increased again during ethylene treatment of fruit after
      harvest. After removal from ethylene SPS transcript levels decreased, only to
      increase again as fruit moved into the climacteric and starch breakdown was
      completed. Exposure to low temperatures also caused an increase in SPS transcript
      level. These results indicate that SPS mRNA increases in kiwifruit in response to
      the presence of new substrate sourced from starch degradation, in response to
      ethylene and in response to low temperature.

PMID- 9520278
TI  - Expression patterns of GASA genes in Arabidopsis thaliana: the GASA4 gene is up
      regulated by gibberellins in meristematic regions.
AB  - The GASA gene family previously identified in Arabidopsis belongs to a wide
      spread class of genes found in mono- and dicotyledonous plants, all structurally
      related to the original GA-regulated GAST1 gene from tomato. They encode small
      peptides (97 to 112 residues) of unknown function sharing a 60 amino acid
      conserved C-terminal domain comprising twelve conserved cysteine residues which
      define a pattern not related to other known cysteine-rich motifs. Northern blot
      hybridization analysis revealed sequential expression of three genes during
      flowering, silique development and seed germination. GASA4 transcripts were
      detected in flower buds. GASA1 transcripts markedly accumulated in siliques,
      about five days after pollination, and correlated with the peak of GA
      biosynthesis at this stage of silique development. GASA3 transcripts accumulated
      at the end of the maturation stage of the silique, and transcripts were still
      present in dry seeds but degraded rapidly during imbibition. In addition, the
      GASA4 gene was again actively transcribed after germination and this expression
      was shown to be dependent on the presence of GAs in GA-deficient mutants.
      Immunoblot analysis confirmed the presence of the GASA4 gene product in flower
      buds, seedlings and roots. We focused on the GASA4 gene and characterized its
      expression. The upstream region (-890 to +128) was fused to the GUS reporter
      gene. GASA4/GUS expression was detected in transgenic Arabidopsis primarily in
      all meristematic regions, including vegetative, inflorescence and floral
      meristems, as well as primary and lateral root tips. In a GA-deficient background
      (ga1-3), GUS activity in the vegetative meristem was detected only in the
      presence of supplied GA. In root and flower meristems, basal GUS activity was
      slightly enhanced by exogenous GA. Interestingly, GA strongly inhibit GUS
      activity in expanding cotyledons and leaves in ga1-3 mutants supplied with
      exogenous GAs, as well as in the wild type. The GA-dependent meristem-specific
      expression pattern suggests that the GASA4 protein plays a role in dividing cells
      rather than in elongating cells.

PMID- 9520279
TI  - Molecular cloning of a novel heat induced/chilling tolerance related cDNA in
      tomato fruit by use of mRNA differential display.
AB  - Chilling injury was circumvented by heat-treating mature green tomatoes
      (Lycopersicon esculentum, cv. Mountain Springs) at 42 degrees C for two days
      prior to storing them at 2 degrees C for one or two weeks, whereas fruits stored
      at 2 degrees C without preheating developed typical chilling injury symptoms and
      failed to ripen at 20 degrees C. Using mRNA differential display and screening of
      the cDNA libraries, we have cloned from tomato fruit a full-length HCT1 cDNA
      (heat induced/chilling tolerance related). The protein ( 17.6 kDa) predicted from
      coding region of HCT1 cDNA has high identity with class II cytosolic small HSPs.
      The gene corresponding to HCT1 cDNA was termed as LeHSP 17.6. Southern-blot
      hybridization indicates that LeHSP 17.6 belongs to a two-member gene family.
      Northern blot analysis indicates the heat-induced transcript of the LeHSP 17.6
      remains up-regulated during subsequent exposure of the fruit to chilling
      temperatures for at least one week and upon transfer to ripening temperatures for
      one day. Fruits which were only chilled show a low level of expression of the
      LeHSP 17.6 transcript. We hypothesize that LeHSP 17.6 may be involved in
      protecting the cell from metabolic dysfunctions leading to ripening failure
      caused by chilling injury. This is the first report of a class II cytosolic
      smHSPs encoding gene in tomato.

PMID- 9520281
TI  - Apple messenger RNAs related to bacterial lignostilbene dioxygenase and plant
      SAUR genes are preferentially expressed in flowers.
AB  - In an attempt to use a differential display procedure to identify organ-specific
      genes in apple, cDNA fragments of two transcripts preferentially expressed in
      flowers were isolated and corresponding full-length cDNA inserts were
      subsequently obtained. One of these clones, Md-FS1, belongs to the SAUR gene
      family, originally identified as a set of auxin-inducible genes in soybean. The
      second one, Md-FS2, encodes a polypeptide with sequence similarities to bacterial
      lignostilbene-alpha,beta-dioxygenase isozymes, which are thought to be involved
      in lignin biodegradation. Northern blot analysis confirmed that both genes are
      preferentially expressed in floral organs at full bloom, while being expressed at
      lower or undetectable levels in vegetative organs (leaves, shoots or roots) as
      well as in immature, green and unopened blossoms. Furthermore, Md-FS1 transcripts
      also appeared to accumulate in vegetative tissues after auxin treatment of
      micropropagated apple shoots.

PMID- 9520280
TI  - Characterisation and promoter analysis of the Arabidopsis gene encoding high
      mobility-group protein HMG-I/Y.
AB  - The single-copy gene encoding the Arabidopsis HMG-I/Y protein was isolated and
      characterised. The gene encodes a protein of 204 amino acid residues and contains
      a single intron of 73 bp. Primer extension analysis indicates that transcription
      starts 115 bp upstream of the translation start and the leader sequence contains
      a short open reading frame of 13 amino acid residues. The 5'-upstream region of
      2117 bp and several 5' deletions were fused to the beta-glucuronidase (GUS)
      reporter gene and transferred to tobacco by Agrobacterium-mediated
      transformation. Analysis of transgenic tobacco plants containing HMG-I/Y promoter
      regions of -2117, -1468 and -707 from the translation start detected GUS activity
      in all organs examined, including roots, stems, leaves and floral organs.
      Deletion from -707 to -185 resulted in a 20-30-fold reduction in GUS activity in
      roots and stems, indicating the presence of important quantitative regulatory
      elements in this region.

PMID- 9520282
TI  - Expression of the Zinnia TED3 promoter in developing tracheary elements of
      transgenic Arabidopsis.
AB  - To determine the regulatory mechanism of gene expression in the early stages of
      tracheary element (TE) differentiation, we isolated and characterized a genomic
      fragment of TED3 whose mRNA is expressed preferentially in differentiating TEs 12
      24 h before morphological changes in the in vitro Zinnia system. Transgenic
      Arabidopsis plants with a chimeric gene of the 537 bp TED3 promoter and the beta
      glucuronidase (GUS) reporter gene indicated the strong expression of the GUS gene
      by the TED3 promoter in TEs, in particular in immature TEs as well as stipules
      and trichomes. GUS expression driven by the promoter was also induced in callus,
      in which GUS activity was localized in immature TEs and slender cells around TEs
      that may be TE precursor cells. The TED3 promoter was not significantly activated
      by wounding. This pattern of expression differed clearly from that of other
      vascular tissue-related genes such as PAL, 4CL, and GRP1.8. The nature of TED3
      promoter enables us to use it to monitor TE differentiation in tissue and to
      introduce foreign genes preferentially into immature TE.

PMID- 9520283
TI  - The Calvin cycle enzyme sedoheptulose-1,7-bisphosphatase is encoded by a light
      regulated gene in Chlamydomonas reinhardtii.
AB  - We have studied the light-dependent expression of the Chlamydomonas reinhardtii
      csbp gene encoding sedoheptulose-1,7-bisphosphatase (SBPase), an enzyme of the
      pentose-phosphate pathway. Expression studies using light/dark-synchronized
      cultures revealed that csbp mRNA abundance increases significantly during
      illumination. We have used a 1.4 kb region upstream of the csbp gene in
      transcriptional fusions to the homologous arylsulfatase-encoding reporter gene
      (ars). In transformants carrying the chimeric csbp/ars reporter gene,
      arylsulfatase activity is detected in the absence of sulfate, a condition under
      which the endogenous ars gene is repressed. Moreover, ars mRNA accumulation is
      dramatically stimulated by light, indicating that 1.4 kb of the csbp 5'
      untranslated region are sufficient to confer light-dependent expression on the
      ars reporter gene.

PMID- 9520284
TI  - Isolation and characterization of a heat-induced gene, hcit2, encoding a novel
      16.5 kDa protein: expression coincides with heat-induced tolerance to chilling
      stress.
AB  - Heat treatment of tomato fruits induces tolerance to chilling injury. We have
      previously shown that specific heat-shock proteins (HSPs) are expressed in heated
      tomato fruits after cold storage. To search for heat-induced genes that are
      expressed at low temperatures, a cDNA library prepared from pre-heated chilled
      tomato fruits was differentially screened. A novel cDNA clone, hcit2, encoding a
      protein of ca. 16.5 kDa, was isolated. The predicted protein contains three
      putative trans-membrane hydrophobic sequences, suggesting that the protein is
      membrane-localized. The expression of hcit2 in fruits was induced by high
      temperature, but not by other stresses such as low temperature, drought or
      anaerobic conditions, and not during fruit ripening. A high level of hcit2
      transcript was found in heated fruits after 2 weeks at 2 degrees C. High
      temperatures also induced hcit2 expression in tomato leaves, flowers and stems.
      The HCIT2 protein may be involved in the acquisition of tolerance to chilling
      injury.

PMID- 9520285
TI  - Generation of killer activity by interleukin-12 of mononuclear cells in malignant
      pleural effusions due to lung cancer.
AB  - In the present study, we examined the ability of interleukin (IL)-12 to generate
      an antitumor effect in the tumor-growing site. Mononuclear cells (MNC) were
      obtained from 12 malignant pleural effusions due to lung cancer in the tumor
      growing site. Non-major-histocompatibility-complex-restricted killer activity,
      examined by 4-h 51Cr release assay against Daudi lymphoma cells as well as
      various lung cancer cell lines (H69 and PC-9), and in vitro production of
      interferon gamma (IFNgamma), measured by enzyme immunoassay, were investigated as
      mediators of antitumor effects of host cells activated by IL-12. IL-12 induced
      killer activity of MNC in pleural effusions (pleural MNC) dose-dependently.
      Moreover, pleural MNC produced a signficant amount of IFNgamma in response to IL-
      12. The killer activities of IL-12-activated blood MNC were higher than those of
      pleural MNC. The supernatants of pleural effusions of these untreated patients
      suppressed killer induction by IL-12 of blood MNC of healthy volunteers. These
      observations suggest that MNC present at the site of growing tumors may act as
      effector cells against lung cancer in the presence of IL-12.

PMID- 9520286
TI  - Immunization of mice with melanoma cells transfected to secrete the superantigen,
      staphylococcal enterotoxin A.
AB  - Immunization of mice with a melanoma vaccine coupled with staphylococcal
      enterotoxin A (SEA) inhibits the growth of primary melanoma tumors in mice. We
      have now successfully transfected B16 cells with the sea gene and have immunized
      C57BL/6 mice subcutaneously once per week for 4 weeks prior to tumor challenge
      with vaccines of irradiated B16 cells or, 4 weeks following tumor challenge of
      naive mice with B16 cells, with irradiated B16 cells transfected with the sea
      gene. Primary tumor growth following both types of treatments was inhibited
      significantly. To characterize immune responses to these immunogens, we examined
      the production of antibodies to the B700 melanoma antigen, the stimulation of
      endogenous IL-2 production, the expression of CD4, CD8, Vbeta and CD25 T cell
      markers, and the induction of NK activity. At 4 weeks following immunization of
      mice, there was a significant increase (P<0.05) in levels of interleukin-2
      production by splenocytes from mice immunized with SEA-secreting B16 cells or
      with the parental B16 cells, compared to controls. Levels of antibodies to the
      B700 melanoma antigen were also significantly higher in mice immunized with the
      SEA-secreting B16 cells, as was expression of CD4, CD8, CD25 and Vbeta T cell
      antigens, particularly CD4. Natural killer cell activity (at various E:T ratios)
      was tenfold higher in splenocytes of mice immunized with SEA-secreting B 16
      cells, and fivefold higher in mice immunized with the parental B16 cells,
      compared to controls. These data confirm the possibility of using irradiated
      murine melanoma cells transfected to secrete SEA in vaccines targeted at
      preventing the development and growth of melanoma.

PMID- 9520287
TI  - Immunotherapy and combined assay of serum levels of carcinoembryonic antigen and
      acute-phase reactants.
AB  - Our previous studies have revealed that gastric and esophageal cancer patients
      with abnormal sialic acid levels had a better response than those with normal
      levels if they received polysaccharide K (PSK), a nonspecific immunomodulator.
      Serum levels of carcinoembryonic antigen (CEA) and acute-phase reactants (APR)
      such as immunosuppressive acidic protein, acid-soluble glycoproteins, alpha1
      antichymotrypsin, and sialic acid were analyzed in 872 gastric cancer patients
      who had undergone resection from March 1979 to September 1993 at the Department
      of Surgery of Tokai University. The patients were categorized into four groups
      according to the preoperative serum levels: group A had normal levels of both CEA
      and APR, group B had abnormal CEA and normal APR levels, group C had a normal CEA
      level and normal levels of one or more APR, and group D had abnormal levels of
      both CEA and of one or more APR. Patients in group D who received PSK showed
      significantly better survival than those without PSK (29.3% versus 6.9%; log-rank
      test, P = 0.0015; Breslow test, P = 0.0042). CEA-positive patients receiving PSK
      therapy exhibited a significantly better survival rate than those without PSK
      (38.1 % versus 18.6%; log-rank test, P = 0.0136; Breslow test, P = 0.0125). Cox's
      regression analysis showed that PSK therapy was significantly related to survival
      in group D, but not in the other groups. We conclude that the combined assay of
      tumor-associated factors (such as CEA) and various nonspecific reactants to the
      presence of cancer (such as immunosuppressive acidic protein, alpha1
      antichymotrypsin, acid-soluble glycoproteins and sialic acid) provides a good set
      of preoperative indicators on which to base the selection of treatment for
      individual gastric cancer patients.

PMID- 9520288
TI  - Cytokine immunotherapy of cancer with controlled release biodegradable
      microspheres in a human tumor xenograft/SCID mouse model.
AB  - A novel biodegradable poly(lactic acid) microsphere formulation was evaluated for
      in vivo cytokine immunotherapy of cancer in a human tumor xenograft/ severe
      combined immunodeficiency (SCID) mouse model. Co-injection of interleukin-2 (IL
      2)-loaded microspheres with tumor cells into a subcutaneous site resulted in the
      complete suppression of tumor engraftment in 80% of animals. In contrast, bovine
      serum-albumin(BSA)-loaded particles or bolus injections of poly(ethylene
      glycol)/IL-2 were ineffective in preventing tumor growth. The antitumor effect of
      IL-2 released by the microspheres was shown to be mediated by the mouse natural
      killer cells. This is the first evidence that the rejection of human tumor
      xenografts can be provoked by the sustained in vivo delivery of IL-2 from
      biodegradable microspheres. The use of poly(lactic acid) microspheres to deliver
      cytokines to the tumor environment could provide a safer and simpler alternative
      to gene therapy protocols in the treatment of cancer.

PMID- 9520289
TI  - Rapid blood clearance of mouse IgG2a and human IgG1 in many nude and nu/+ mouse
      strains is due to low IgG2a serum concentrations.
AB  - We reported previously that the blood clearance of injected mouse IgG2a was
      extremely rapid in many strains of nude and nu/+ mice. In an attempt to determine
      the cause of this phenomenon, the levels of endogenous IgG2a in the blood of
      these mice was assayed. It was found that the serum level of IgG2a was extremely
      low in many of these mice, below 50 microg/ml, which is 20-100 times lower than
      the expected normal value. Great heterogeneity between individual mice was
      observed in their blood level of IgG2a, and there was an excellent correlation
      between low blood IgG2a levels and rapid clearance of injected IgG2a. Thus, the
      blood IgG2a levels are so low that a novel, previously undescribed effect occurs,
      namely the rapid clearance of small amounts of injected IgG2a. The clearance is
      due primarily to binding sites in the spleen and liver. The low level of
      endogenous IgG2a is not due to the lack of a thymus, since it occurs in nu/+ as
      well as nude mice, but can probably be attributed to the very clean environment
      in which these mice are raised. In assays of sera from approximately 50 mouse
      strains, low IgG2a levels were found in all nude colonies and also in some normal
      mouse strains. Some nude mice displayed relatively normal IgG2a clearance rates
      despite having low levels of endogenous IgG2a. In repeated bleedings of
      individual mice, IgG2a levels were found to fluctuate greatly. A similar
      clearance effect was observed with a human IgG1 Ab injected into mice. This rapid
      clearance of injected IgG, of certain subclasses, represents a practical problem
      for many experiments in which antibodies are used for diagnosis or therapy, and
      several methods of circumventing the problem are discussed.

PMID- 9520290
TI  - Molecular characterisation of tumour infiltrating lymphocytes in oral squamous
      cell carcinoma.
AB  - Oral squamous cell carcinoma (OSCC) is often associated with a lymphocytic
      infiltrate that is believed to represent an in vivo immune reaction to the tumour
      cells. In this study, the tumour-infiltrating lymphocytes (TIL) associated with
      primary OSCC were characterised molecularly in six newly-diagnosed patients to
      determine the nature of the immune response to the primary tumour. The primary
      tumours in three of the six patients were associated with a moderate to dense
      CD8+ T cell infiltrate whilst the cellular infiltrate in the other primary
      tumours was sparse. The CD3+ T cells were also HLA-DR+. In all cases, there were
      few CD56+ cells, suggesting that TIL were predominantly T cells bearing the
      alpha/beta T cell receptors (TCR). The TCR Vbeta repertoire of TIL in these six
      cases was analysed. TCR Vbeta gene usage by TIL was heterogeneous. A restricted
      usage of TCR Vbeta genes by TIL was evident in two tumours associated with a
      dense CD3+ T cell infiltrate. In one of these, there was histological evidence of
      tumour cell destruction by TIL. Further analysis of the predominant TCR Vbeta
      gene family used by TIL in this individual showed a unique in-frame nucleotide
      sequence in 100% of the transcripts. This recurrent transcript was not detected
      in the peripheral blood of this patient, indicating a local T cell clonal
      expansion in the vicinity of the tumour. Overall, these results suggest that
      activation and clonal expansion of T cells occurs and may play a role in local
      tumour destruction in OSCC.

PMID- 9520291
TI  - Interleukin-2: hope in cases of cisplatin-resistant tumours.
AB  - To establish whether or not local low-dose recombinant interleukin-2 (rIL-2)
      therapy might result in therapeutic benefit for ovarian cancer patients treated
      with cisplatin, the antitumour effects of rIL-2 and of combined treatment with
      cisplatin and rIL-2 in a mouse ovarian tumour (MOT) model were studied. In
      addition, some possible mechanistic aspects underlying the observed antitumour
      responses were analysed. MOT cells were injected i.p. into syngeneic,
      immunocompetent, female C3HeB mice. Tumour-bearing mice received i.p. treatment
      with cisplatin, rIL-2 or both. The MOT tumour appeared to be hardly responsive to
      treatment with cisplatin only or rIL-2 only. In contrast, combined local
      treatment with low doses of cisplatin (1 and 5 mg/kg body weight) and rIL-2
      (60000 U/day) resulted in an effective antitumour response in MOT-bearing mice.
      Complete rejection of the i.p. (local) tumour occurred in up to 60% of the cases.
      In vitro studies showed that cisplatin and rIL-2 do not have cumulative direct
      toxic effects on MOT cells. Mice cured after combined treatment with cisplatin
      and rIL-2 were not able to reject a rechallenge with tumour cells, indicating
      that these mice had not developed immunity to the tumour. Analysis of tumour
      associated leucocytes, however, showed that combined treatment with cisplatin and
      rIL-2 did result in enhanced non-specific cytolytic activity of peritoneal
      leucocytes. We have thus demonstrated that, in the MOT model, combined local
      treatment with low doses of cisplatin and of rIL-2 is far more effective than
      therapy with cisplatin alone. Non-specific cytotoxicity of leucocytes appears to
      be involved in antitumour responses induced by combined treatment with cisplatin
      and rIL-2. These results suggest that, in human ovarian carcinoma, much better
      results may be obtained with the combined treatment of cisplatin and low (non
      toxic) doses of rIL-2 than with cisplatin only. This may also apply to cisplatin
      resistant ovarian carcinoma.

PMID- 9520292
TI  - Cathepsin D antigenic epitopes identified by the humoral responses of ovarian
      cancer patients.
AB  - Previous studies implicated cathepsin D as one commonly recognized target of
      tumor-reactive immunoglobulins from ovarian cancer patients. These
      immunoglobulins are shown to be immunoreactive with both the 52-kDa procathepsin
      D and the 32-kDa mature cathepsin D derived from the UL-1 ovarian cancer cell
      line. Whether the carbohydrate domains or the core protein were associated with
      its immunogenicity was analyzed with cathepsin D isolated from tunicamycin
      treated UL-1 cells. No significant difference was detected in the
      immunoreactivity of patient serum with the glycosylated and deglycosylated forms
      of the cathepsin D, suggesting that patient humoral responses are directed
      primarily against the core protein. To define the antigenic epitopes of cathepsin
      D, tryptic fragments were prepared from UL-1-derived procathepsin D. The epitopes
      of the core protein recognized by sera from more than one patient were identified
      using a peptide-specific enzyme-linked immunosorbent assay and microsequencing of
      positive immunoreactive peptides. This protocol identified four epitopes: two
      peptides within the propeptide, a third at the carboxy terminus and the fourth at
      the glycosylation site of the mature enzyme. This approach to the identification
      of specific antigenic epitopes may be useful in defining effective targets for
      directed active immunotherapy against cancer.

PMID- 9520293
TI  - Modification of ricin A chain, by addition of endoplasmic reticulum (KDEL) or
      Golgi (YQRL) retention sequences, enhances its cytotoxicity and translocation.
AB  - A pKK expression system in Escherichia coli was used to produce recombinant ricin
      A chain (rRTA) and rRTA modified by addition of organelle-specific amino acid
      retention sequences, including KDEL (an endoplasmic reticulum, ER, lumen
      retention signal), KKMP (an ER membrane retention signal), YQRL (a trans-Golgi
      network retention signal) and KFERQ (a lysosome-targeting signal) to the C
      terminus of rRTA. The toxicities of these RTA mutants were assessed in Jurkat
      cells following fluid-phase endocytosis. rRTA-KDEL and rRTA-YQRL were
      significantly more cytotoxic for Jurkat cells than rRTA, rRTA-KKMP or rRTA-KFERQ.
      This difference did not result from signal(KDEL or YQRL)-mediated binding of
      these RTA mutants to the cell surface. Reconstituted ER and Golgi vesicles have
      been employed to assess translocation of rRTA and mutant rRTA. RTA-KDEL and RTA
      YQRL respectively exhibited 6.7-fold and 6.1-fold more protection against papain
      digestion in reconstituted ER vesicles and 2.2-fold and 1.8-fold more protection
      in reconstituted Golgi vesicles, than unmodified rRTA. These mutants were
      reassociated with ricin B chain to form holotoxins. The mutant RTA-KDEL and RTA
      YQRL holotoxins were 3.8-fold and 1.5-fold more cytotoxic for target cells,
      respectively, than ricin produced using unmodified rRTA. Our results suggest that
      both ER and the trans-Golgi network may play important roles in the intracellular
      trafficking and translocation of ricin A chain.

PMID- 9520295
TI  - Interference of sugars with the binding of biotin to streptavidin and avidin.
AB  - Streptavidin and avidin have found widespread use as detection reagents in
      immunology, biochemistry and cell biology due to their high affinity binding to
      biotin, but the cellular functions of these proteins are not known. We have found
      that various sugars interfere with the binding of streptavidin and avidin to
      biotin. Mannose was most effective in inhibiting the binding to biotin followed
      by other saccharides. The inhibitory effect is most probably due to interactions
      of the sugars with residues in the binding pocket of streptavidin and avidin for
      biotin. These results show that great caution has to be exercised in the
      evaluation of experiments conducted with these detection reagents in the presence
      of sugars.

PMID- 9520294
TI  - Stable expression of a retrovirally transferred adhesion molecule in a human
      melanoma-specific cytotoxic T lymohocyte clone.
AB  - The adoptive transfer of in vitro generated tumor-specific cytotoxic T
      lymphocytes (CTL) is considered a promising perspective in cancer therapy. One
      possible drawback lies in the inappropriate homing of in vitro cultured
      lymphocytes, which could be circumvented by introducing the appropriate targeting
      molecules. Here we describe a protocol that allows a rapid and stable
      transfection of cytotoxic T cell clones. As a model system we used a CTL clone
      specific for the melanoma-associated antigen gp100 and a cDNA encoding for murine
      CD14 containing the variant exen v10 which is supposed to facilitate lymphocyte
      homing towards the skin. CD44v10 cDNA was ligated into the retroviral vector pMV
      7, which was used to transfect the ecotropic GP-E-86 and the amphotropic PA317
      cells. After several cycles of transduction to increase the viral titre,
      supernatants of the amphotropic PA317-CD44v10 line were used for transduction of
      CD44v10 into a human CTL clone. After three cycles of transduction at 12-h
      intervals, low but stable expression of CD44v10 was observed throughout the
      culture period of 10 weeks. The phenotype of the transduced CTL clone was
      unaltered and the cytotoxic potential was only slightly reduced as compared to
      the parental clone. The efficiency of stable transduction within a period of 1
      week makes the protocol well suited for the in vivo transfer of transduced cells
      and, in the special case, should guarantee appropriate homing of the transduced
      CTL clone.

PMID- 9520296
TI  - Fusions to the cholera toxin B subunit: influence on pentamerization and GM1
      binding.
AB  - The cholera toxin B (CTB) subunit has been used extensively in vaccine research
      as a carrier for peptide immunogens due to its immunopotentiating properties,
      where coupling has been obtained either by genetic fusion or chemical
      conjugation. For genetically fused immunogens both N- and C-terminal fusions have
      been used. Only shorter extensions have previously been evaluated and in some
      reports these fusions have impaired the biological functions of CTB, such as the
      ability to form pentamers and to adhere to its cell receptor, the GM1
      ganglioside. Here we report the first systematic study where the same fusion
      partner has been used for either C-terminal, N-terminal or dual fusions to CTB.
      The serum albumin binding region (BB, approximately 25 kDa) from streptococcal
      protein G, which is known to fold independently of N- or C-terminal fusions, was
      selected as fusion partner. The three fusion proteins CTB-BB, BB-CTB and BB-CTB
      BB were expressed in Escherichia coli, where they were efficiently secreted to
      the periplasmic space, and could be purified by affinity chromatography on human
      serum albumin (HSA) columns. The CTB fusion proteins were compared for their
      ability to form pentamers, by gel electrophoresis and size-exclusion
      chromatography, and it was concluded that all three fusion proteins were able to
      pentamerize. Interestingly, the C-terminal fusion to CTB showed most efficient
      pentamerization, while the dual fusion was much less efficient. Purified pentamer
      fractions from all three fusions where found to react to a monoclonal antibody
      described to react only to pentameric forms of CTB. In addition, the purified
      pentamer fractions were analyzed in an enzyme-linked immunosorbent assay (ELISA)
      for their ability to bind GM1, and it was found that the C-terminal fusion (CTB
      BB) showed significant GM1-binding, but that also the N-terminal and dual CTB
      fusion proteins bound GM1, although less efficiently. The implications of the
      results for the design and use of CTB fusion proteins as subunit vaccines are
      discussed.

PMID- 9520297
TI  - An immune response to ovalbumin covalently coupled to liposomes is prevented when
      the liposomes used contain doxorubicin.
AB  - It is now well established that liposomes with surface associated proteins are
      immunogenic. Repeated administration of protein coated liposomes elicits the
      generation of antibodies and the elimination of proteoliposome increases markedly
      in animals 'immunized' with such liposomes. This immune response compromises the
      therapeutic potential of liposomal formulations that rely on the use of protein-
      or peptide-based targeting ligands to enhance cell specificity. Strategies to
      suppress or inhibit such immune responses must be developed if this technology is
      going to prove therapeutically viable. This study evaluates whether an immune
      response to a protein, covalently attached to liposomes by a thioether bond
      between N-succinimidyl-3-(2-pyridyldithio)propionate (SPDP)-modified-protein and
      N-(4-(P-maleimidophenyl)butyryl) (MPB)-activated lipids, can be suppressed when
      the liposomes used contain the anti-cancer drug doxorubicin. To assess this, the
      highly immunogenic protein ovalbumin was conjugated onto liposomes composed of
      distearoylphosphatidylcholine/cholesterol (DSPC/Chol) with sufficient
      poly(ethylene glycol)-modified distearoyl phosphatidylethanolamine (PEG-DSPE) (2
      mol%) to prevent liposome aggregation during protein coupling and to engender
      increased circulation lifetimes. The immune response to these liposomes with and
      without encapsulated doxorubicin was measured by: (1) monitoring liposome
      elimination after 3 weekly i.v. injections in C3H/HeJ mice and (2) measuring the
      anti-ovalbumin antibody levels by an ELISA assay. One week after a single dose of
      ovalbumin-coated PEG liposomes (50 microg protein/mouse) the immune response
      resulted in rapid elimination of a second dose of ovalbumin-coated PEG liposomes.
      Rapid liposome elimination was correlated to generation of high levels (> 9
      microg/ml plasma) of circulating anti-ovalbumin IgG. In contrast, anti-ovalbumin
      antibodies were not detected when the liposomes used contained doxorubicin.
      Plasma elimination of these drug loaded protein coated liposomes decreased
      following repeated weekly i.v. doses, an effect that is consistent with liposomal
      doxorubicin mediated suppression of phagocytic cells in the liver.

PMID- 9520298
TI  - A sensitive ELISPOT assay to detect low-frequency human T lymphocytes.
AB  - We extended the sensitivity of the ELISPOT assay by including an antigen-driven
      proliferation step prior to a final restimulation with antigen and irradiated
      antigen presenting cells (APCs). This improved sensitivity made the modified
      ELISPOT assay better suited to the detection of rare or low frequency T
      lymphocytes than the standard ELISPOT assay or alternatives such as limiting
      dilution analysis or in situ hybridization. Use of ELISA-grade plastic or
      polyvinylidene difluoride (PVDF) plates for the detection of different cytokines
      improved the signal-to-noise ratio for counting cytokine spots, and use of video
      computer imaging software improved objective quantitation. Analysis of antigen
      reactive peripheral blood mononuclear cells (PBMC) from multiple sclerosis (MS)
      patients using both the traditional and our modified ELISPOT assay demonstrate a
      > 10-fold increase in numbers of myelin basic protein (MBP)-responsive T cells
      detected (an average of less than 1 spot forming cell (SFC) per 2 x 10(5) PBMC
      with the standard assay compared to 19 SFC per 2 x 10(5) PBMC with the modified
      assay). In addition, the modified ELISPOT assay could be performed with frozen
      PBMC, which permitted greater flexibility in sample processing, multiple use of a
      single sample as an internal standard, and simultaneous analysis of samples
      collected at different time points. This modified ELISPOT assay has many
      applications, including analysis of cytokine profiles in rare T cell populations,
      identification of antigen-responsive individuals as PBMC donors for T lymphocyte
      cloning or for therapeutic intervention, and assessment of vaccine or therapeutic
      efficacy as a surrogate clinical marker.

PMID- 9520299
TI  - Evaluation of the interferon-gamma ELISPOT-assay for quantification of peptide
      specific T lymphocytes from peripheral blood.
AB  - ELISPOT assays for detection of antigen specific HLA class I restricted T
      lymphocytes have recently been developed. Reliable quantitation of T cell
      frequencies is crucial for the monitoring of specific cancer vaccines. We have
      evaluated the accuracy of quantitative results obtained with the IFN-gamma
      ELISPOT assay and both sensitivity and specificity obtained with several pairs of
      antibodies was compared. The detection system was tested with IFN-gamma coupled
      latex beads and the quantitation of influenza specific T cells with several sets
      of dilution experiments. The reproducibility of the quantitative results was
      established. Only one pair of monoclonal antibodies had an acceptable
      specificity. In a serial dilution, almost 100% of IFN-gamma-coated beads could be
      detected. Furthermore, the number of influenza-peptide specific spots correlated
      closely with (a) the number of antigen specific T cells derived from an influenza
      peptide specific T cell line diluted in PBMC, and (b) the number of CD8+ T cells
      diluted in autologous CD8-depleted PBMC. In three healthy individuals and three
      cohorts of healthy volunteers, the number of influenza-peptide specific spots was
      highly reproducible. The data presented here demonstrate that the frequency of
      peptide specific CD8+ T cells can be reliably determined from peripheral blood
      with the IFN-gamma ELISPOT assay.

PMID- 9520300
TI  - Quantitation of messenger RNA by competitive RT-PCR: a simplified read out assay.
AB  - A competitive RT-PCR method that permits reliable quantification of minute
      amounts of reverse-transcribed mouse lymph node mRNA is described. Using this
      technique, an absolute number of cDNA copies ranging from 10(3) to 10(5) can be
      determined, with a precision superior to 25%. The standard templates described in
      the present study permit the quantitation of beta-actin, IFN gamma, IL2, IL3,
      IL4, IL10, IL12 (p40 subunit), TGF beta 1, inducible nitric oxide synthase, ELAM
      1, VCAM-1, and ICAM-1 mouse mRNA. The expression of a particular transcript is
      normalized to an arbitrary number of actin transcripts. The standard templates
      and wild-type cDNA have nearly identical sequences, but they can be distinguished
      by unique restriction sites. Known amounts of these standard templates, are co
      amplified with serial dilutions of the cDNA derived from the mRNA of interest.
      Oligonucleotide primer pairs possessing 3' octamers found infrequently in the
      mouse genome (< or = 0.26 x 10(-6)) are used to amplify sequences, chosen to
      contain no GC stretches longer than 8 (PCRare software) (Griffais et al., 1991).
      Samples of each PCR product are digested separately with restriction
      endonucleases unique either for the wild-type or the standard amplicon. The
      quantitation of the test product and the standard product is easily carried out
      following their electrophoresis in an ethidium bromide-stained agarose gel.

PMID- 9520301
TI  - A method for production and determination of histamine releasing activity from
      human peripheral blood mononuclear cells.
AB  - Histamine releasing factors, i.e. cytokines capable of inducing histamine release
      from basophils or mast cells, have been suggested to be involved in the
      pathogenesis of, for example, allergic late-phase reactions. Here we describe a
      controlled method for production and determination of histamine releasing
      activity (HRA) from human peripheral blood mononuclear cells (MNC). MNC were
      incubated with concanavalin A (Con A) for 2 h and cultured for another 40 h in
      fresh serum free medium. The culture supernatants were concentrated 19-25 fold by
      ultrafiltration (molecular weight cut-off: 3000 Da). The preparations of HRA
      induced dose- and Ca2+-dependent histamine release from leukocytes. Supernatants
      of parallel cultures of unstimulated MNC did not induce histamine release. The
      HRA was neither due to exogenous histamine releasing compounds (e.g. Con A) nor
      to residual histamine in the preparations of HRA. The kinetics of HRA induced
      histamine release (half-maximal release after > 40 min) were slower and more
      protracted than those of anti-IgE induced histamine release. However, based on a
      comparison between HRA induced histamine release from leukocytes and purified
      (97%) basophils, this did not appear to be due to an indirect effect on the
      basophils. Finally, neither the production of nor the response to HRA was
      dependent on the allergic status of the donor.

PMID- 9520302
TI  - Quantification of cytokine mRNA expression by RT PCR in samples of previously
      frozen blood.
AB  - In order to facilitate cytokine mRNA detection in blood cells, we have developed
      a highly reproducible and easily performed RNA isolation method for use with
      whole blood. Previously frozen human whole blood samples were lysed in guanidine
      thiocyanate solution to isolate total RNA. After reverse transcription a PCR
      method was applied to detect beta-actin and cytokine mRNA expression (interleukin
      (IL)2, IL4, IL10, tumor necrosis factor alpha (TNF alpha) and interferon gamma
      (IFN gamma)). The presence of cDNA was confirmed by agarose gel electrophoresis
      and quantitated on-line using sequence-specific fluorochrome labeled internal
      oligonucleotide probes. This quantitative method is based on the cleavage of
      fluorescent dye labeled probes by the 5' --> 3' endonuclease activity of the Taq
      DNA polymerase during PCR and measurement of fluorescence intensity by a Sequence
      Detector System. The signal generated was directly proportional to the starting
      copy number of target molecules in the sample over 6 log concentrations and
      quantitative analysis of cDNA concentrations was performed in comparison to beta
      actin or cytokine cDNA standards. mRNAs coding for beta-actin and TNF alpha were
      readily detectable in cDNAs prepared from the whole blood of eight healthy
      donors, while the other cytokines were expressed in lower amounts (IFN gamma,
      IL10) or were undetectable (IL2, IL4). The assay described is highly
      reproducible, requires no post PCR manipulation of the amplicons and permits the
      analysis of several hundred PCR reactions per day. Using this method it is
      possible to detect and quantify cytokine mRNA expression reliably in small
      amounts of previously frozen blood even after storage of samples for at least
      several months.

PMID- 9520303
TI  - Frequency of human anti-FVIII antibodies in humanized SCID mice elicited by
      recombinant deleted factor VIII and by a plasma derived factor VIII.
AB  - SCID mice were grafted with human PBL (hu-PBL-SCID) from healthy or haemophilia A
      donors. Those containing human and no murine Ig in their plasma, were injected
      with 100 U VIII:Ag of a plasma derived (pd) FVIII or recombinant deleted Factor
      VIII (FVIII deltaII) and with 10 microg of tetanus toxoid as control immunogen.
      The frequency and the intensity of the humoral specific responses were measured
      in 253 mice humanized with PBL from 13 different donors. There was no significant
      difference in the frequency or intensity of the anti-FVIII immune responses to pd
      FVIII and FVIII deltaII. Neutralizing antibodies were only detected in the plasma
      of mice humanized with cells from haemophiliacs having FVIII inhibitors in their
      blood. The immune responses observed in hu-PBL-SCID mice correlated with the
      immune status of the corresponding human donor.

PMID- 9520304
TI  - Construction and characterization of a radio-iodinatable mutant of recombinant
      human CD4.
AB  - Recombinant soluble human CD4 (rsCD4) has been used in iodinated form to study
      the interaction of CD4 with its ligands. However, the utility of [125I]-rsCD4 is
      limited because rsCD4 is inefficiently iodinated and the iodinated protein is
      poorly active. The iodination properties of rsCD4 most likely reflect the poor
      accessibility of the tyrosine residues, apparent from the available X-ray
      structures. We have generated an iodinatable mutant of rsCD4 by substituting Tyr
      for Phe(179) in the flexible, solvent-exposed C-terminal region of rsCD4(183), a
      truncated form of CD4 that consists of the first 183 residues of CD4 and includes
      the binding sites for HIV-1 gp120 and MHC class II molecules. When F179Y
      rsCD4(183) is iodinated under trace-labeling conditions, the efficiency of 125I
      incorporation and the percentage of iodinated molecules that are active are much
      enhanced compared with WT rsCD4. Moreover, trace-labeled [125I]-F179Y rsCD4(183)
      has the same affinity for HIV-1 rgp120 as unlabeled WT rsCD4. The improved
      activity of trace-labeled [125I]-F179Y rsCD4(183) appears to be due to effective
      competition by Y179 for reactive iodine species that, in WT rsCD4, react with
      traces of denatured protein and/or with residues critical for activity or
      conformational integrity. The incorporation of accessible tyrosine residues may
      improve the iodinatibility of a protein both by introducing a readily iodinatable
      residue and by protecting sensitive proteins from adverse reactions.

PMID- 9520305
TI  - A rapid evaluation of phagocytosis and killing of Candida albicans by CD13+
      leukocytes.
AB  - Flow cytometry can be adopted for routine monitoring of the immune functions of
      human polymorphonuclear leukocytes (PMNs) in several disease states. We recently
      developed a rapid and reproducible assay for the evaluation of the phagocytosis
      and killing of Candida albicans blastospores by human PMNs. Whole blood
      leukocytes were incubated with opsonized fluorescein isothiocyanate-labeled (FITC
      labeled) blastospores for phagocytosis and killing assays. To discriminate
      between ingested, membrane-bound and free C. albicans blastospores, ethidium
      bromide (EtBr) was added to the samples prior to the flow cytometric analysis.
      EtBr induces a loss of green fluorescence in non-phagocytized C. albicans
      blastospores. Phagocytosis is determined by gating the phagocytes and calculating
      the percentage of phagocyte-associated green fluorescent cells. Intracellular
      killing is determined by first lysing phagocytes by hypotonic shock and then
      adding propidium iodide (PI) in order to identify red dead blastospores. Killing
      is measured in terms of the percentage of double-marked blastospore cells. We
      suggest that this method is a reliable and inexpensive technique to evaluate the
      immune reactivity of PMNs and peripheral blood monocytes (PBMs) in cases of
      immunosuppression.

PMID- 9520306
TI  - Analysis of the alpha/beta T-cell receptor repertoire by competitive and
      quantitative family-specific PCR with exogenous standards and high resolution
      fluorescence based CDR3 size imaging.
AB  - The characterization of the human T-cell receptor (TCR) repertoire in various
      physiological and pathological conditions has become an important tool in studies
      of the immune response. Therefore, a number of PCR based strategies for the
      semiquantitative analysis of the TCR repertoire have been described. Family
      specific amplification of TCR cDNA has been employed in a number of studies often
      with contradictory results. We have developed a strategy utilizing exogenous
      standards with homologous primer binding sites for the quantitative analysis of
      the alpha/beta T-cell receptor repertoire. This system allows the detection of
      even minute differences in T-cell populations based on quantitative PCR (Q-PCR)
      and competitive PCR (C-PCR). Results presented here demonstrate that expansions
      of T-cell subsets as defined by the specificity of the variable gene segments can
      be readily monitored when exceeding 1% of the total repertoire. In addition, the
      proposed method reveals direct information of CDR3 size heterogeneity and can be
      used to estimate the T-cell repertoire complexity and monitor clonal expansions.
      We discuss variables such as cell number and experimental conditions influencing
      accuracy and reproducibility of the analyses. We have used this protocol based on
      non-radioactive techniques for characterization of the fine specificity of the T
      cell repertoire in peripheral and organ-infiltrating T-lymphocytes. The analyses
      revealed information about polyclonal or clonal expansion of T-cells in vivo and
      in vitro following various stimuli such as superantigenic stimulation of T-cell
      subsets as well as antigen-driven shaping of the alpha/beta T-cell repertoire in
      autoimmune and infectious diseases.

PMID- 9520307
TI  - Morphological and behavioral aspects of interhemispheric integration.

PMID- 9520309
TI  - Phil Bryden's spoken comments on Gina Grimshaw's, Marie Banich's, and Joe
      Hellige's symposium talks.

PMID- 9520308
TI  - Mark Philip Bryden.

PMID- 9520310
TI  - Integration and interference in the cerebral hemispheres: relations with
      hemispheric specialization.
AB  - The two hemispheres of the brain often perform complementary computations and
      make unique contributions to task performance. This study examines the
      interaction of linguistic (left hemisphere) and prosodic (right hemisphere)
      information in speech processing. An individual differences approach is used in
      which interference between linguistic and prosodic processes in a Stroop-like
      task is compared between individuals who process the two dimensions in opposite
      hemispheres (complementary specialization) vs. those who process both dimensions
      in the same hemisphere (noncomplementary specialization). Complementarity was not
      related to interference in any way. This finding is consistent with the
      hypothesis of Chiarello and Maxfield (1996) that interference is equivalent
      between and within hemispheres when it arises in a response selection stage.

PMID- 9520311
TI  - The missing link: the role of interhemispheric interaction in attentional
      processing.
AB  - Although interhemispheric interaction via the callosum is most often conceived as
      a mechanism for transferring sensory information and coordinating processing
      between the hemispheres, it will be argued here that the callosum also plays an
      important role in attentional processing. Experiments will be presented that
      support this viewpoint, both when attention is conceptualized as a resource and
      when it is conceptualized as a selective mechanism for gating sensory
      information. Interhemispheric interaction is posited to aid attentional
      processing because it allows for a division of labor across the hemispheres, and
      allows for parallel processing so that operations performed in one hemisphere can
      be insulated from those executed in the other. Given this additional role for
      interhemispheric processing, it is suggested that the corpus callosum should be
      considered a component in the network of neural structures that underlie
      attentional control.

PMID- 9520312
TI  - Relationships between brain morphology and behavioral measures of hemispheric
      asymmetry and interhemispheric interaction.
AB  - Thirty adult males identified consonant-vowel-consonant nonword trigrams
      projected briefly to the left visual field (right hemisphere), the right visual
      field (left hemisphere) or to both visual fields (and hemispheres)
      simultaneously. Magnetic resonance images of the brains of these same individuals
      provided measurements of the length of the Sylvian fissure and surface area of
      the planum temporale within each hemisphere as well as measurements of the
      midsagittal area of the corpus callosum. Both behavioral and morphological
      asymmetries were consistent with those found in previous studies. In addition,
      there were several relationships between brain morphology and trigram naming. For
      example, as the length of the right-hemisphere Sylvian fissure increased to
      become more like the typical length of the left-hemisphere Sylvian fissure, there
      were fewer errors of trigram identification and attention was distributed more
      quickly or evenly across the three letters contained in the display. In addition,
      as the midsagittal area of the corpus callosum increased, the percentage of
      errors increased on left visual field trials, but not on right visual field or
      bilateral trials, suggesting that an increase in corpus callosum size may be
      indicative of greater functional isolation of the two hemispheres.

PMID- 9520313
TI  - The dynamics of interhemispheric collaboration and hemispheric control.
AB  - This article reviews recent models of how the two hemispheres collaborate to
      facilitate efficient information processing. The strengths and weaknesses of
      behavioral techniques and structural and functional neuroimaging techniques are
      considered as they apply to these problems. The role of the corpus callosum as an
      equilibrator of activation between the two hemispheres is discussed and linked
      with its role as a dynamic modulator for the mobilization of hemispheric
      resources. Issues related to metacontrol and dynamic fluctuations in hemispheric
      control are also considered.

PMID- 9520314
TI  - On the reliability and validity of noninvasive laterality measures.
AB  - The purpose of the present study was to quantify the reliability and validity of
      laterality effects obtained with noninvasive measures. A meta-analytic approach
      was used with 88 significance levels pertaining to reliability data and 11
      significance levels concerning the validity of the measures. Results showed that
      reliability is affected by a number of procedural factors. In general,
      reliability was found to be at a moderate level. The validity of laterality
      measures was found to be significant but low. These findings suggest that more
      empirical work is needed to investigate and to improve the validity and
      reliability of the tasks used in the assessment of laterality effects.

PMID- 9520316
TI  - Categorical inference is not a tree: the myth of inheritance hierarchies.
AB  - One enduring principle of rational inference is category inclusion: Categories
      inherit the properties of their superordinates. In five experiments, I show that
      people do not consistently apply this principle when evaluating categorical
      arguments involving natural categories and a single nonexplainable predicate such
      as all electronic equipment has parts made of germanium, therefore all stereos
      have parts made of germanium. Participants frequently did not apply the category
      inclusion rule despite affirming the relevant categorical relation (e.g., stereos
      are electronic equipment). They failed to apply the rule even when categories
      were universally quantified unambiguously. Instead, judgments tended to be
      proportional to the similarity between premise and conclusion categories. Neglect
      of category inclusion relations was observed using arguments concerning natural
      kinds, artifacts, and social kinds.

PMID- 9520317
TI  - The effects of operator implementation cost on planfulness of problem solving and
      learning.
AB  - This paper explores the idea that problem solving search strategies are chosen so
      as to optimize performance within the constraints of a particular situation. Four
      experiments are reported that examine the hypothesis that the cost of performing
      an operation affects "planfulness"--the level of planning during problem solving.
      The first experiment investigated problem solving with the 8-puzzle and compared
      strategies adopted when there was a high versus a low cost of making a move,
      manipulating cost in terms of command length. The second experiment used protocol
      analysis to provide more direct evidence for increased planning. The third and
      fourth experiments looked at the effects of these different strategies on
      learning: the third examined how problem solving performance on a direct
      manipulation interface is affected by prior problem solving experience in the
      same domain with either a high cost or low cost command-driven interface,
      demonstrating improved performance as a result of training on an interface with
      high cost operations; the fourth experiment, like the third, examined the effects
      of prior problem solving experience with either a high cost or low cost interface
      on subsequent problem solving performance in a different domain using a direct
      manipulation interface showing no effect to training interface on subsequent
      performance.

PMID- 9520318
TI  - On the lawfulness of grouping by proximity.
AB  - The visual system groups close things together. Previous studies of grouping by
      proximity have failed to measure grouping strength or to assess the effect of
      configuration. We do both. We reanalyze data from an experiment by Kubovy and
      Wagemans (1995) in which they briefly presented multi-stable dot patterns that
      can be perceptually organized into alternative collections of parallel strips of
      dots, and in which they parametrically varied the distances between dots and the
      angles between alternative organizations. Our analysis shows that relative
      strength of grouping into strips of dots of a particular orientation approximates
      a decreasing exponential function of the relative distance between dots in that
      orientation. The configural or wholistic properties that were varied--such as
      angular separations of the alternative organizations and the symmetry properties
      of the dot pattern--do not matter. Additionally, this grouping function is robust
      under transformations of scale in space (Experiment 1) and time (Experiment 2).
      Grouping of units which are themselves the result of grouping (i.e., pairs of
      dots; Experiment 3) also follows our nonconfigural rule.

PMID- 9520319
TI  - Hox group 3 paralogs regulate the development and migration of the thymus,
      thyroid, and parathyroid glands.
AB  - The thymus, thyroid, and parathyroid glands in vertebrates develop from the
      pharyngeal region, with contributions both from pharyngeal endoderm and from
      neural crest cells in the pharyngeal arches. Hoxa3 mutant homozygotes have
      defects in the development of all three organs. Roles for the Hoxa3 paralogs,
      Hoxb3 and Hoxd3, were investigated by examining various mutant combinations. The
      thyroid defects seen in Hoxa3 single mutants are exacerbated in double mutants
      with either of its paralogs, although none of the double-mutant combinations
      resulted in thyroid agenesis. The results indicate that the primary role of these
      genes in thyroid development is their effect on the development and migration of
      the ultimobranchial bodies, which contribute the parafollicular or C-cells to the
      thyroid. Hoxb3, Hoxd3 double mutants show no obvious defects in the thymus or
      parathyroids. However, the removal of one functional copy of Hoxa3 from the
      Hoxb3, Hoxd3 double mutants (Hoxa3 +/-, Hoxb3-/-, Hoxd3-/-) results in the
      failure of the thymus and parathyroid glands to migrate to their normal positions
      in the throat. Very little is known about the molecular mechanisms used to
      mediate the movement of tissues during development. These results indicate that
      Hoxa3, Hoxb3, and Hoxd3 have highly overlapping functions in mediating the
      migration of pharyngeal organ primordia. In addition, Hoxa3 has a unique function
      with respect to its paralogs in thymus, parathyroid, and thyroid development.
      This unique function may be conferred by the expression of Hoxa3, but not Hoxb3
      nor Hoxd3, in the pharyngeal pouch endoderm.

PMID- 9520320
TI  - Defective development of the embryonic liver in N-myc-deficient mice.
AB  - The mechanisms involved in the formation and the differentiation of the liver
      remain unclear despite extensive studies. To investigate these events in mouse
      hepatic development, we have taken advantage of the N-myc mutant mouse line which
      exhibits abnormal liver development. N-myc mutant embryos die between 11.5 and
      12.5 days postcoitum most probably from heart failure. In the present study, we
      report that at 11.5 days of gestation, extensive apoptosis restricted to the
      hepatocytes occurred in N-myc mutant liver when compared to wild-type samples.
      Moreover, the number of hematopoietic cells is reduced in the mutant liver.
      During early liver organogenesis, the N-myc gene is expressed in tissues involved
      in the induction and the differentiation of the hepatocytes. At 11.5 days
      postcoitum, both c-myc and N-myc genes are expressed in the liver. While c-myc is
      expressed at a high level in the organ per se, N-myc expression is mostly
      confined to the peripheral layer of the liver which will generate the Glisson's
      capsule. Taken together, the expression pattern of N-myc in the liver and the
      specific apoptosis of hepatocytes observed in N-myc mutants indicate that N-myc
      is required for hepatocyte survival and suggest that it is involved in the
      genetic cascade leading to normal liver development.

PMID- 9520321
TI  - Immunolocalization of alpha-tubulin, gamma-tubulin, and CENP-E in male rat and
      male mouse meiotic divisions: pathway of meiosis I spindle formation in mammalian
      spermatocytes.
AB  - Recent findings on cell division suggest that differences exist in spindle
      organization not only between mitotic and meiotic systems, but also between
      female and male meiosis. In mammals, this has been difficult to demonstrate due
      to lack of appropriate methods. By taking advantage of the strict organization
      and ordered kinetics of mammalian spermatogenesis, we harvested highly enriched
      populations of dividing mouse and rat spermatocytes using transillumination
      assisted micro-dissection of seminiferous tubules. In the spermatocytes, we
      examined the localization and distribution of microtubules, centrosomes, and
      kinetochores at different phases of the first meiotic division using
      immunohistochemistry with antibodies against alpha-tubulin, gamma-tubulin, and
      CENP-E, respectively. Fluorescence and confocal microscope analysis of dividing
      spermatocytes provides evidence that the formation of the male mammalian meiosis
      I spindle differs from that of female meiosis and mitosis. A short (1-2 microns)
      bipolar aggregate of microtubules is nucleated by two adjacent centrosomes
      located next to the nucleus. After nuclear envelope breakdown, adjacent
      centrosomes and the short spindle become surrounded by the mass of paired meiotic
      chromosomes. At prometaphase the distance between the centrosomes increases
      resulting in elongation of the microtubule arrays and eventually formation of a
      full-length metaphase spindle (12-14 microns). Based on these results we suggest
      a model for spindle morphogenesis in mammalian spermatocytes.

PMID- 9520322
TI  - Late specification of Veg1 lineages to endodermal fate in the sea urchin embryo.
AB  - Single blastomeres of the sixth-cleavage veg1 and veg2 tiers of
      Strongylocentrotus purpuratus embryos were labeled with DiI lineage tracer, and
      the disposition of the progeny was followed through the blastula and gastrula
      stages in order to determine their respective endodermal and ectodermal
      contributions. In the endoderm of postgastrula embryos, veg1-derived cells
      constituted nearly all of the prospective hindgut and about half of the
      prospective midgut, while veg2-derived cells made up the prospective foregut and
      half the midgut. Oral veg1 clones consistently contributed more cells to endoderm
      than aboral veg1 clones. Oral veg1 clones extended along the archenteron up to
      the foregut region, while aboral veg1 clones contributed only small numbers of
      hindgut cells but large patches of ectoderm cells that extended out to the
      prospective larval vertex. The oral/aboral asymmetry in veg1 allocations was also
      demonstrated using chimeric embryos, the animal halves of which were labeled with
      a rhodamine-dextran. Lineages expressing the vegetal plate marker Endo16 were
      more precisely determined by combining lineage tracer injection with whole-mount
      in situ hybridization. Endo16 expression was found in all cells that are going to
      participate in gastrulation. Recruitment of new cells to the Endo16 domain occurs
      in advance of the actual invagination of those cells. During the blastula stages
      Endo16 expression expands radially until all cells in the veg2 lineages express
      this gene. The first phase of gastrulation, including the normal buckling of the
      vegetal plate and primary invagination of the archenteron, involves only the
      Endo16-expressing cells of the veg2 lineages. As the archenteron begins to
      elongate, marking the onset of the second phase of gastrulation, there is an
      asymmetric expansion of Endo16 into the veg1-derived cells that will contribute
      to the hindgut and midgut in accordance with lineage tracing observations. The
      results indicate a relatively late specification of veg1-derived cells, resulting
      in late recruitment to the periphery of the vegetal plate territory as
      gastrulation proceeds. Differential recruitment of veg1-derived cells on the oral
      side of the embryo introduces an oral bias to gastrulation by disproportionately
      increasing the number of cells on the oral side that are competent to participate
      in gastrulation.

PMID- 9520323
TI  - Expression of a twist-related gene, Bbtwist, during the development of a lancelet
      species and its relation to cephalochordate anterior structures.
AB  - Mesoderm formation plays a crucial role in the establishment of the chordate body
      plan. In this regard, lancelet embryos develop structures such as the anteriorly
      extended notochord and the lateral divertecula in their anterior body. To
      elucidate the developmental basis of these structures, we examined the expression
      pattern of a lancelet twist-related gene, Bbtwist, from the late gastrula to
      larval stages. In late-gastrula embryos, the transcripts of Bbtwist were detected
      in the presumptive first pair of somites and the middorsal wall of the primitive
      gut. The expression of Bbtwist was then upregulated in the lateral wall of
      somites and the notochord. At the late-neurula stage, it was also expressed in
      the anterior wall of the primitive gut, as well as in the evaginating lateral
      diverticula. No signal was detected in the left lateral diverticulum when it was
      separated from the gut, while in the right one, the gene was expressed later
      during the formation of the head coelom in knife-shaped larvae, and in the
      anterior part of the notochord in the same larvae. In 36-h larvae, only faint
      expression was detected in the differentiating notochordal and paraxial mesoderm
      in the caudal region. These expression patterns suggest that Bbtwist is involved
      in early differentiation of mesodermal subsets as seen in Drosophila and
      vertebrates. The expression in the anterior notochord may be related to its
      anterior expansion. The expression in the anterior wall of the primitive gut and
      its derivative, the lateral diverticula, suggests that lancelets share the
      capability to produce a mesodermal population from the tip of the primitive gut
      with nonchordate deuterostome embryos.

PMID- 9520324
TI  - Changes in cyclin B during oocyte maturation and early embryonic cell cycle in
      the newt, Cynops pyrrhogaster: requirement of germinal vesicle for MPF
      activation.
AB  - When full-grown oocytes of the newt Cynops pyrrhogaster were treated with
      progesterone in O-R2 solution containing antibiotics, approximately 85% of the
      oocytes completed meiosis synchronously. Maturation-promoting factor (MPF)
      activity appeared just before germinal vesicle breakdown (GVBD) and the oocytes
      maintained high MPF activity throughout metaphase I and metaphase II of meiosis.
      A slight decrease of MPF activity was observed at the first polar body emission.
      The distribution of cyclin B1 was investigated with anti-cyclin B1 antibody. No
      cyclin B1 was found in the oocytes before progesterone treatment. Cyclin B1
      appeared in the cortex of animal hemispheres, especially around and inside
      germinal vesicle just before GVBD. A large amount of cyclin B1 accumulated at
      metaphase I, approximately half disappeared at the first polar body emission, and
      then cyclin B1 accumulated again at metaphase II. An inactive form of cdc2 kinase
      was observed in both the germinal vesicles and the oocyte cytoplasm, while an
      active form appeared at the M phase. No MPF was observed in the oocytes from
      which the germinal vesicle had been removed. A cdk7-like molecule was localized
      in the germinal vesicle, but not in oocyte cytoplasm, indicating that inactive
      cdc2 kinase associated with cyclin B1 derived from cytoplasm is activated by
      phosphorylation in the germinal vesicle. The changes in the amount of cyclin B1
      were synchronous with the first cell cycle after fertilization. Cyclin B1 was
      primarily localized in the cortex of the animal hemisphere. A shift in band
      mobility upon electrophoresis of cyclin B1 was observed from samples taken during
      the cell cycle; this shift was probably due to the protein's phosphorylation
      state.

PMID- 9520325
TI  - Disruption of scale development by Delta-1 misexpression.
AB  - Notch and its ligands are molecules known to be involved in many cell fate
      decisions. Due to the proposed role of this signaling system in the choice
      between feather and smooth skin fate in the embryonic chick, we sought to test
      whether Notch signaling may also play a role in determining scale fate. Notch-1
      and -2, Serrate-1 and -2, and Delta-1 are expressed in the scales throughout
      their development. Misexpression of chick Delta-1 using a replication-competent
      retrovirus results in regions of scale loss. In addition, feather buds are often
      observed on some of the scuta scales. These results suggest a model in which
      Delta can act as an inhibitor of skin appendage fate as well as a promoter of
      feather fate.

PMID- 9520326
TI  - Developmental regulation of mossy fiber afferent interactions with target granule
      cells.
AB  - In an in vitro model system based on purified target cerebellar granule neurons
      and explants of afferents, pontine mossy fiber afferents stop growing through
      contact-mediated mechanisms when they encounter granule neurons. Here we studied
      the developmental regulation of the stop signal posed by granule cells and the
      response of mossy fibers to the stop signal in two culture systems. Granule
      neurons presented in slices or as dissociated cells from postnatal day (P) 4 and
      P7 cerebellum were more potent in the arrest of P0 pontine neurites than younger
      (P0-P2) or older (up to P14) granule neurons. In contrast, pontine neurites at
      embryonic day (E) 18, during their period of normal growth toward the cerebellum,
      grew extensively on both cerebellar slices of all ages from P0 to P10 and
      dissociated P4 granule neurons. When E18 explants were maintained for 2 days
      before plating in medium conditioned by neonatal cerebellar cells, E18 pontine
      explants were rendered more responsive to the stop signal from P4 granule cells.
      These results indicate that the stop signal, and the response of afferents to it,
      are developmentally regulated. Moreover, factors within the target region may
      initiate these interactions.

PMID- 9520328
TI  - The dispersion of clonally related cells in the developing chick telencephalon.
AB  - Lineage analysis in the chick telencephalon was carried out using a library of
      retroviral vectors. Clones were analyzed in posthatch day 14-21 animals for the
      phenotype and final locations of sibling cells. Clones often contained multiple
      types of neurons and glia. Clones of more than four cells almost always crossed
      functional boundaries. They were dispersed primarily along the rostrocaudal axis
      or in multiple directions, e.g., along the rostrocaudal and mediolateral axes. In
      order to begin to understand how the final patterns of dispersion were reached,
      embryonic tissue was examined. Radial migration, apparently supported by radial
      glial cells, occurred within the proliferative zones in all clones. In contrast
      to the migration of cells in the mammalian telencephalon, no tangential migration
      within the proliferative zones was observed at any age examined. However,
      beginning at embryonic day 4.5, tangential migration in the mantle zone in
      multiple directions was observed among the majority of clones. This type of
      migration occurred as soon as a mantle zone became apparent. It appeared that the
      tangential migration was not along radial glial processes. As in the mammalian
      telencephalon and chick diencephalon, dispersion among clonally related cells in
      the chick telencephalon is frequent, is extensive, and results from tangential
      migration in a variety of directions.

PMID- 9520327
TI  - Microtubule organization during the early development of the parthenogenetic egg
      of the hymenopteran Muscidifurax uniraptor.
AB  - The origin of the zygotic centrosome is an important step in developmental
      biology. It is generally thought that sperm at fertilization plays a central role
      in forming the functional centrosome which subsequently organizes the first
      mitotic spindle. However, this view is not applicable in the case of
      parthenogenetic eggs which develop without the sperm contribution. To clarify the
      problem of the origin of the zygotic centrosome during parthenogenetic
      development, we studied a hymenopteran, Muscidifurax uniraptor. Antitubulin
      antibody revealed that after activation several asters assembled in the egg
      cytoplasm. The number of asters varied in relation to the cell cycle. They became
      visible from anaphase of the first meiotic division and increased in number as
      meiosis progressed, reaching a maximum at the first mitosis. From anaphase
      telophase of the first mitosis they decreased in number and were no longer found
      during the third mitotic division. To elucidate the nature of these asters we
      performed an ultrastructural study with transmission electron microscopy and
      immunofluorescence with antibodies against anti-gamma-tubulin and CP190. In this
      way we showed the presence in these asters of centrosomal components and
      centrioles. Our observations suggest that the cytoplasm of Muscidifurax eggs
      contains a pool of inactive centrosomal precursor proteins becoming able to
      nucleate microtubules into well-defined asters containing centrioles after
      activation.

PMID- 9520329
TI  - Zebrafish TrkC1 and TrkC2 receptors define two different cell populations in the
      nervous system during the period of axonogenesis.
AB  - We identified previously five distinct trk genes in the zebrafish. The structures
      of two of these, TrkC1 and TrkC2, are most similar to mammalian TrkC. Detailed
      sequence comparisons reported here indicate that although the similarities to
      TrkC are greatest in those regions of the extracellular domain implicated in
      ligand binding, the two sequences also differ significantly in these regions.
      Whole-mount in situ hybridization experiments in the early embryo revealed full
      length trkC1 but no trkC2 transcripts in the cranial ganglia and in a subset of
      Rohon-Beard neurons. At the same time, full-length trkC2 but no trkC1 transcripts
      were detected laterally in the spinal cord, in the caudal hindbrain, in
      reticulospinal neurons of rhombomeres 4, 5, and 6, and in the midbrain. Both
      types of transcripts were expressed in clusters of cells in the dorsal
      telencephalon and the nucleus of the tract of the postoptic commissure. These
      results suggest distinct functions of trkC1 and trkC2 in nervous system
      development. The expression patterns define two different neuronal populations in
      the zebrafish.

PMID- 9520330
TI  - The muscleblind gene participates in the organization of Z-bands and epidermal
      attachments of Drosophila muscles and is regulated by Dmef2.
AB  - We report the embryonic phenotype of muscleblind (mbl), a recently described
      Drosophila gene involved in terminal differentiation of adult ommatidia. mbl is a
      nuclear protein expressed late in the embryo in pharyngeal, visceral, and somatic
      muscles, the ventral nerve cord, and the larval photoreceptor system. All three
      mbl alleles studied exhibit a lethal phenotype and die as stage 17 embryos or
      first instar larvae. These larvae are partially paralyzed, show a
      characteristically contracted abdomen, and lack striation of muscles. Our
      analysis of the somatic musculature shows that the pattern of muscles is
      established correctly, and they form morphologically normal synapses.
      Ultrastructural analysis, however, reveals two defects in the terminal
      differentiation of the muscles: inability to differentiate Z-bands in the
      sarcomeric apparatus and reduction of extracellular tendon matrix at attachment
      sites to the epidermis. Failure to differentiate both structures could explain
      the partial paralysis and contracted abdomen phenotype. Analysis of mbl
      expression in embryos that are either mutant for Dmef2 or ectopically express
      Dmef2 places mbl downstream of Dmef2 function in the myogenic differentiation
      program. mbl, therefore, may act as a critical element in the execution of two
      Dmef2-dependent processes in the terminal differentiation of muscles.

PMID- 9520331
TI  - BMP1-related metalloproteinases promote the development of ventral mesoderm in
      early Xenopus embryos.
AB  - Bone morphogenetic protein 1 (BMP1) is a metalloproteinase closely related to
      Drosophila Tolloid (Tld). Tld regulates dorsoventral patterning in early
      Drosophila embryos by enhancing the activity of Dpp, a member of the TGF-beta
      family most closely related to BMP2 and BMP4. In Xenopus BMP4 appears to play an
      essential role in dorsoventral patterning, promoting the development of ventral
      fates during gastrula stages. To determine if BMP1 has a role in regulating the
      activity of BMP4, we have isolated cDNAs for Xenopus BMP1 and a novel closely
      related gene that we have called xolloid (xld). Whereas xbmp1 is uniformly
      expressed at all stages tested, the initial uniform expression of xld becomes
      localized to two posterior ectodermal patches flanking the neural plate and later
      to the inner ectoderm of the developing tailbud. xld is also expressed in dorsal
      regions of the brain during tailbud stages and is especially abundant in the
      ventricular layer of the dorsal hindbrain caudal to the otic vesicle.
      Overexpression of either gene inhibits the development of dorsoanterior
      structures in whole embryos and ventralizes activin-induced dorsal mesoderm in
      animal caps. Since ventralization of activin-induced animal caps can be blocked
      by coinjecting a dominant-inhibitory receptor for BMP2 and BMP4, we suggest a
      role for BMP1 and Xld in regulating the ventralizing activity of these molecules.

PMID- 9520332
TI  - A key function for alphav containing integrins in mesodermal cell migration
      during Pleurodeles waltl gastrulation.
AB  - During cleavage of Pleurodeles waltl amphibian embryos, inner cells of the
      blastocoel roof (presumptive ectodermal and mesodermal cells) organize a
      fibrillar extracellular matrix (ECM) containing fibronectin on their basal
      surface by a beta1-integrin-dependent process. This matrix is used as a migratory
      substrate by mesodermal cells during gastrulation. While alpha5beta1 integrin is
      expressed on both ectodermal and mesodermal cell surface, we have shown
      previously that alphav containing integrins are essentially restricted to the
      surface of mesodermal cells (Alfandari, D., Whittaker, C. A., DeSimone, D. W.,
      and Darribere, T., Dev. Biol. 170, 249-261, 1995). To investigate the function of
      alphav integrins during gastrulation, we have generated a function blocking
      antibody directed against the extracellular domain of the Pleurodeles integrin
      alphav subunit. The antibody did not prevent fibronectin fibril formation,
      whereas an antibody against the alpha5beta1 integrin did. When injected into the
      blastocoel, the antibody against integrin alphav subunit perturbed gastrulation
      and further development in a stage-dependent manner. Developmental defects were
      correlated to an abnormal positioning of the mesoderm layer. In vitro, the
      antibody blocked spreading of mesodermal cell to fibronectin or blastocoel roof
      ECM but not their attachment. In contrast, the antibody directed against the
      alpha5beta1 integrin inhibited both cell attachment and spreading to the same
      substrates. We propose that the alpha5beta1 integrin is required for fibronectin
      assembly into fibrils and mesodermal cell attachment to the blastocoel roof ECM,
      while the alphav containing integrins are necessary for cell spreading, and
      possibly migration, on this complex network.

PMID- 9520333
TI  - Cell death during development of testis and cerebellum in the mutant mouse
      weaver.
AB  - The murine mutation weaver confers early death during development on cells in
      testes, cerebellum, and midbrain. The results reported here support the
      hypothesis that the action of weaver is intrinsic to testes and independent of
      Sertoli cells: germ cells are the only testicular cell type seen to die in weaver
      homozygotes, while Sertoli cell-dependent development of the blood testis barrier
      is normal. This report includes characterization of patterns of germ cell death
      and cerebellar granule cell death in homozygous weavers with respect to that seen
      during normal development by in situ end-labeling of DNA and high-magnification
      light microscopy. Comparison of the spatial distribution of dying cells in the
      weaver's cerebellum with that of dividing cells revealed disarray in the external
      germinal zone. The results show that cells vulnerable to weaver die by apoptotic
      and nonapoptotic mechanisms and indicate that weaver-induced cell death is not
      the consequence of extended naturally occurring developmental cell death,
      although their timing overlaps. Thus, although the death of cells in each region
      is likely to be caused by the same mutation, a base pair substitution in the G
      protein-coupled inwardly rectifying potassium channel 2 gene, the cell death
      program activated differs depending on cell type.

PMID- 9520335
TI  - Editorial
AB  - Copyright

PMID- 9520336
TI  - Mechanisms of susceptibility to mouse liver carcinogenesis.

PMID- 9520334
TI  - Formation of functional tight junctions in Xenopus embryos.
AB  - Formation of the blastocoel in early Xenopus embryos was studied with a novel
      biotin-permeability assay and newly generated tight junction markers. The
      blastocoel forms at the first cleavage division since functional tight junctions
      which excluded biotin and established a segregated intraembryonic compartment
      were found at the 2-cell and all subsequent developmental stages. Unexpectedly,
      tight junctions before the 64-cell stage were not at their normal apical
      positions, but were found deep in the embryos, up to 200 micron from the apical
      surface. In these positions, the tight junctions left large areas of ion
      permeable lateral membranes exposed to the extraembryonic environment, explaining
      why electrophysiological experiments record a decrease in embryonic input
      resistances concomitant with early cleavage stages. Immunohistochemistry revealed
      that the recessed tight junctions did not influence the distribution of C
      cadherin and Na+,K+ATPase. Both markers were present apical to recessed tight
      junctions, indicating that the maintenance of polarization of these basolateral
      markers does not require tight junctions. With further development, tight
      junctions assumed an increasingly apical location until, by the 2000-cell stage,
      they occupied their conventional positions between the blastomeres at the
      apical/lateral membrane boundaries.

PMID- 9520337
TI  - Common mechanism of toxicity: a case study of organophosphorus pesticides.
AB  - The Food Quality Protection Act of 1996 (FQPA) requires the EPA to consider
      "available information concerning the cumulative effects of such residues and
      other substances that have a common mechanism of toxicity ... in establishing,
      modifying, leaving in effect, or revoking a tolerance for a pesticide chemical
      residue." This directive raises a number of scientific questions to be answered
      before the FQPA can be implemented. Among these questions is: What constitutes a
      common mechanism of toxicity? The ILSI Risk Science Institute (RSI) convened a
      group of experts to examine this and other scientific questions using the
      organophosphorus (OP) pesticides as the case study. OP pesticides share some
      characteristics attributed to compounds that act by a common mechanism, but
      produce a variety of clinical signs of toxicity not identical for all OP
      pesticides. The Working Group generated a testable hypothesis, anticholinesterase
      OP pesticides act by a common mechanism of toxicity, and generated alternative
      hypotheses that, if true, would cause rejection of the initial hypothesis and
      provide criteria for subgrouping OP compounds. Some of the alternative hypotheses
      were rejected outright and the rest were not supported by adequate data. The
      Working Group concluded that OP pesticides act by a common mechanism of toxicity
      if they inhibit acetylcholinesterase by phosphorylation and elicit any spectrum
      of cholinergic effects. An approach similar to that developed for OP pesticides
      could be used to determine if other classes or groups of pesticides that share
      structural and toxicological characteristics act by a common mechanism of
      toxicity or by distinct mechanisms.

PMID- 9520338
TI  - Bioavailability and pharmacokinetics of microencapsulated 1,3-dichloropropene in
      rats.
AB  - The potential oral toxicity of 1,3-dichloropropene (1,3-D) has been evaluated in
      a number of dietary toxicity studies. The relatively high vapor pressure of 1,3
      D, its short half-life in drinking water, and its reactivity with constituents of
      feed necessitated the use of a microencapsulated formulation (starch-sucrose
      shell) of 1,3-D in these studies. The bioavailability of ingested
      microencapsulated 1,3-D was determined by characterizing and comparing the
      kinetics of 1,3-D in the blood of female F344 rats coadministered
      microencapsulated 1,3-D and neat 13C-1,3-D (25 mg/kg each) via gavage. Blood
      concentrations of total or cis- and trans-isomers of 1,3-D in treated rats were
      determined using gas chromatography-mass spectroscopy (GC-MS) or in situ membrane
      extraction MS. Urine was also collected and analyzed by GC-MS for the presence of
      the mercapturate excretion product of 1,3-D [N-acetyl-S-(3-chloropropenyl-2)-L
      cysteine; 1,3-DMA]. Blood levels of 1,3-D and 13C-1,3-D displayed similar
      kinetics, peaking within 10 min of dosing followed by a rapid biphasic
      elimination. Higher peak blood levels and greater blood curve areas (AUC) were
      attained for trans- than cis-1,3-D and 13C-1,3-D and greater amounts of cis- than
      trans-1,3-DMA and 13C-1,3-DMA were excreted in the urine consistent with the
      known rapid and disproportionate glutathione conjugation of the cis-isomer in the
      gastric mucosa. Slightly higher cis-1,3-D than cis-13C-1,3-D blood levels and
      AUCs were also consistently noted while the reverse was true for urinary
      excretion of cis-13C-1,3-DMA and cis-1,3-DMA suggesting that 1,3-D derived from
      microencapsulated test material may be absorbed and/or metabolized in the stomach
      mucosa at a slightly slower rate than that from neat material. The latter,
      however, would be of no consequence during the administration of 1,3-D to animals
      via their diets as competing test materials would not be present and 1,3-D blood
      kinetics were unaffected. Overall, the results of this study demonstrate the
      ready bioavailability of microencapsulated 1,3-D and rapid elimination of 1,3-D
      from the blood of rats.

PMID- 9520340
TI  - Gender- and age-specific cytotoxic susceptibility to benzene metabolites in
      vitro.
AB  - Benzene, a widely used compound, is a known carcinogen and hematopoietic
      toxicant. Several studies have shown gender and age differences in the responses
      to benzene-induced hematotoxicity. It is not known if these differences in
      response are due to age- or gender-associated metabolic differences or to age- or
      gender-associated differences in the susceptibilities of the target cells. In
      order to address this issue, mouse colony-forming units-erythroid (CFU-e, an
      erythroid precursor cell particularly susceptible to benzene toxicity) were
      cultured in the presence of either individual benzene metabolites or binary
      mixtures of these metabolites. CFU-e were obtained from unexposed age-matched
      adult male and female (both virgin and pregnant) Swiss Webster (SW) mice and from
      SW male and female 16-day fetuses. The metabolites used were phenol,
      hydroquinone, catechol, benzoquinone, and trans, trans-muconic acid. The
      concentrations of the individual metabolites used were 10, 20, and 40 microM.
      Binary mixtures of metabolites were prepared using the lowest concentrations of
      the individual metabolites that caused cytotoxicity. These concentrations were 10
      microM for hydroquinone, catechol, and benzoquinone, and 40 microM for phenol and
      muconic acid. In general, the CFU-e from adult females (both virgin and pregnant)
      were more resistant to the toxic effects of the individual metabolites than CFU-e
      from other subjects. CFU-e from adult males were more susceptible to the
      cytotoxic effects of hydroquinone and benzoquinone than CFU-e from other subjects
      and CFU-e from both male and female fetuses were highly sensitive to the toxic
      effects of catechol. On the other hand, CFU-e from adult males were less
      susceptible to the cytotoxic effects of catechol than CFU-e from other subjects.
      Similar results were observed with binary mixtures of metabolites. CFU-e from
      adult males were more susceptible to the binary mixtures than CFU-e from virgin
      females and CFU-e from fetal males were more susceptible than CFU-e from fetal
      females. In addition, CFU-e from fetuses were more 'resistant than CFU-e from
      adults to the cytotoxic effects of those binary mixtures that did not contain
      catechol. In contrast, binary mixtures containing catechol were more toxic to
      fetal cells than to adult cells. These results suggest that differences in
      benzene hematotoxicity associated with gender and age may be due, at least in
      part, to intrinsic factors at the level of the target cell rather than solely to
      age- or gender-related differences in the metabolism of benzene.

PMID- 9520339
TI  - Evaluation of octamethylcyclotetrasiloxane (D4) as an inducer of rat hepatic
      microsomal cytochrome P450, UDP-glucuronosyltransferase, and epoxide hydrolase: a
      28-day inhalation study.
AB  - Repeated inhalation exposure to octamethylcyclotetrasiloxane (D4) produces a
      reversible and dose-related hepatomegaly and proliferation of hepatic endoplasmic
      reticulum in rats. However, the effects of D4 on the expression of cytochrome
      P450 enzymes have not been evaluated. In the present study, the time course for
      changes in hepatic microsomal cytochrome P450 enzyme expression following
      repeated inhalation exposure to D4 vapors was determined in male and female
      Fischer 344 rats. Animals were exposed to D4 vapor at concentrations of 70 and
      700 ppm, via whole body inhalation for 6 h/day, 5 days/week for 4 weeks.
      Specified animals were euthanized on exposure days 3, 7, 14, 21, and 28.
      Microsomal fractions were prepared from fresh liver by differential
      centrifugation. Enzyme activity as well as immunoreactive protein levels of
      several cytochrome P450 enzymes (CYP), epoxide hydrolase, and UDP
      glucuronosyltransferase (UDPGT) were evaluated. The time course for enzyme
      induction was monitored by measuring 7-ethoxyresorufin O-deethylase (EROD) and 7
      pentoxyresorufin O-depentylase (PROD) activities on days 3, 7, 14, 21, and 28.
      CYP1A1/2 activity, as determined by EROD activity, was increased approximately 2-
      to 3-fold over the exposure period. However, an examination of immunoreactive
      protein revealed no induction of CYP1A1 and a suppression of CYP1A2 in the 700
      ppm D4 group. In comparison, CYP2B1/2 enzyme activity, as determined by PROD, was
      significantly increased as early as day 3 in both the 70 and 700 ppm D4 groups of
      male and female rats. Overall, PROD activity on day 28 was induced more than 10
      fold in the 70 ppm D4 groups and more than 20-fold in the 700 ppm D4 groups. The
      increase in PROD activity was paralleled by a comparable increase in CYP2B1/2
      immunoreactive protein. There was a modest (2- to 3-fold) increase in CYP3A1/2
      activity and immunoreactive protein, as determined by 6 beta-hydroxylation of
      testosterone and Western blot analysis. Expression of CYP enzymes was at or near
      maximum by day 14 and remained relatively constant throughout the exposure
      period. On day 28, epoxide hydrolase activity and immunoreactive protein were
      induced (2- to 3-fold) in a dose-dependent manner. Only slight changes in the
      expression and activity of UDPGT were detected, and these did not appear to be
      dose related. Thus, repeated inhalation exposure to D4 induces CYP enzymes and
      epoxide hydrolase in a manner similar to that observed for phenobarbital (PB).
      Therefore, D4 can be described as a "PB-like" inducer of hepatic microsomal
      enzymes in the Fischer 344 rat.

PMID- 9520341
TI  - Symposium overview: toxicity of non-coplanar PCBs.
AB  - Research into the mechanism of toxicity of PCBs has focused on the Ah receptor.
      However, it is becoming increasingly clear that certain ortho-chlorine
      substituted, non-coplanar PCB congeners having low affinity for the Ah receptor
      exhibit important biological activities. Actions of non-coplanar PCB congeners in
      a variety of biological systems have been discovered and the mechanisms for these
      effects are being elucidated. The objectives of this symposium are to examine the
      state of knowledge concerning the mechanisms of toxic action of non-coplanar PCBs
      and to identify similarities and differences using a variety of biological
      systems. Effects to be considered will include: neurotoxicity, estrogenicity,
      insulin release, neutrophil function, calcium regulation, and relevant signal
      transduction systems. Finally, the symposium addresses the need to consider non
      coplanar congeners within the context of risk assessment. The use of Ah-receptor
      binding and its associated biological effects to assess the total toxicity of
      PCBs may no longer be defensible because of the actions produced by non-coplanar
      congeners. This symposium provides documentation for that conclusion and focuses
      attention on emerging mechanisms of PCB action that have received relatively
      little attention to date. The topics presented should be of interest to
      toxicologists interested in mechanisms of action, in PCB risk assessment, and in
      regulatory toxicology.

PMID- 9520342
TI  - Comparative carcinogenicity in Sprague-Dawley rats of the polychlorinated
      biphenyl mixtures Aroclors 1016, 1242, 1254, and 1260.
AB  - A comprehensive chronic toxicity and carcinogenicity study was conducted on a
      series of Aroclors (1016, 1242, 1254, and 1260). Each Aroclor was assessed at
      multiple dietary concentrations, ranging from 25 to 200 ppm, for 24 months in
      male and female Sprague-Dawley rats. Liver toxicity was indicated by elevated
      serum enzyme activity (AST, ALT, and GGT), elevated serum cholesterol
      concentration, decreases in hematologic parameters (RBC, Hb, and Hct),
      hepatocellular hypertrophy, an increased incidence of altered hepatocellular
      foci, and an increased incidence of hepatocellular neoplasms (primarily
      adenomas). Liver toxicity was distinctly more severe in females than in males.
      The incidence of hepatocellular neoplasms was highly sex-dependent (females >>
      males), differed between Aroclor mixtures and, for females, increased with dose
      and followed the general incidence pattern of Aroclor 1254 > Aroclor 1260
      approximately Aroclor 1242 > Aroclor 1016. A significant response (p < 0.05) in
      males was seen only for the high dose of Aroclor 1260. A small increase in the
      incidence of thyroid gland follicular cell adenomas was noted in males for
      Aroclors 1242, 1254, and 1260, with the incidence being uniform across dose
      groups and Aroclor mixtures. For females, increased survival relative to controls
      was observed for all Aroclor treatment groups. A significantly decreased trend in
      the incidence of mammary gland neoplasms compared to control was also noted for
      females receiving Aroclors 1242, 1254, and 1260.

PMID- 9520344
TI  - Pre- and postnatal toxicity of the HMG-CoA reductase inhibitor atorvastatin in
      rats.
AB  - Atorvastatin is a potent inhibitor of the enzyme 3-hydroxy-3-methylglutaryl
      coenzyme A (HMG-CoA) reductase, which catalyzes the conversion of HMG-CoA to
      mevalonate and constitutes the rate-limiting step in the biosynthesis of
      cholesterol. Steroid hormones derived from cholesterol, as well as mevalonate and
      its isoprenoid derivatives, provide important contributions to the maternal
      animal during pregnancy and lactation, as well as to the growth and development
      of the offspring; these contributions may potentially be influenced by inhibition
      of HMG-CoA reductase. To investigate the effects of atorvastatin on various
      aspects of reproduction and development, female Sprague-Dawley rats received 0,
      20, 100, or 225 mg/kg daily by gavage from gestation day 7 through lactation day
      20. Maternal toxicity, characterized by morbidity/mortality (13%), reduced body
      weight gain and food consumption, and pathologic lesions in the nonglandular
      mucosa of the stomach, occurred at 225 mg/kg. Offspring survival at birth and
      during the neonatal period at 225 mg/kg was reduced relative to control by up to
      45%, and 28% of litters had no viable offspring by 10 days postpartum. Additional
      effects on offspring included reduced body weight during the neonatal and
      maturation periods (100, 225 mg/kg), delayed appearance of pinnae detachment and
      incisor eruption (225 mg/kg), impaired rotorod performance (females only; 100,
      225 mg/kg), reduced acoustic startle responding (males only; 20, 100, 225 mg/kg),
      and transient effects on shuttle avoidance (females only; 225 mg/kg). No
      treatment-related effects were observed on offspring reproduction. In a separate
      experiment, a single dose of 10 mg/kg atorvastatin administered to female Wistar
      rats on gestation day 19 or lactation day 13 provided evidence of placental
      transfer and excretion into the milk. Results of this study indicate that pre-
      and postnatal administration of atorvastatin to female rats produces
      developmental toxicity in their offspring via in utero and/or lactational
      exposure, and in the presence or absence of maternal toxicity.

PMID- 9520343
TI  - Methyl tertiary butyl ether-induced endocrine alterations in mice are not
      mediated through the estrogen receptor.
AB  - Chronic exposure to methyl tertiary butyl ether (MTBE) altered the rodent tumor
      incidence of endocrine-sensitive tissues and decreased the incidence of estrogen
      dependent uterine cystic hyperplasia in mice. To test the hypothesis that changes
      in the incidence of tumors in female B6C3F1 mice after MTBE exposure are
      secondary to endocrine alterations, we exposed female mice to the carcinogenic
      dose of MTBE vapor (8000 ppm) for 3 or 21 days or 4 or 8 months under conditions
      similar to a previous 2-year bioassay. MTBE exposure significantly decreased body
      weight gain and ovary and pituitary weight at 4 and 8 months and uterine weight
      at all time points. After 8 months of exposure, MTBE significantly increased the
      length of the estrous cycle by increasing the mean number of days in both the
      estrus and the nonestrus stages. Histological evaluation of H&E-stained tissues
      showed a decrease in the number of uterine glands after subchronic MTBE exposure.
      DNA synthesis, as measured by the incorporation of 5-bromo-2'-deoxyuridine
      (BrdU), was decreased in uterine glandular and luminal epithelial cells after
      MTBE exposure for 3 or 21 days or 4 or 8 months. MTBE exposure decreased the
      number of epithelial layers in the cervix and vagina at all time points. DNA
      synthesis was decreased in cervical and vaginal epithelium after 21 days of MTBE.
      Decreased zona reticularis of adrenal glands was found after 4 and 8 months of
      MTBE exposure without changes in BrdU incorporation. MTBE did not competitively
      bind to estrogen receptor. MTBE exposure did not alter serum estrogen levels or
      alter the location or intensity of estrogen receptor immunoreactivity in the
      uterus, cervix, and vagina. These data indicate that while MTBE exposure causes
      multiple endocrine-related tissue and cellular responses, these effects are not
      mediated through the estrogen receptor.

PMID- 9520345
TI  - Comparison of fresh and room-aged cigarette sidestream smoke in a subchronic
      inhalation study on rats.
AB  - Two experimental types of cigarette sidestream smoke (SS) were compared in a
      subchronic inhalation study on rats. Fresh SS (FSS) was generated continuously
      from the reference cigarette 2R1. Room-aged SS (RASS) was generated by aging FSS
      for 1.5 h in a room with noninert surfaces with materials typically found in
      residences or offices. Male Sprague-Dawley rats were head-only exposed to three
      dose levels of each SS type and to filtered, conditioned fresh air (sham
      exposure) for 6 h/day, 7 days/week, for 90 days. Room-aging resulted in decreased
      concentrations of various SS components, e.g., total particulate matter (TPM) and
      nicotine, while other components, such as carbon monoxide (CO), were not
      affected. The CO concentrations were 6, 13, and 28 ppm for both SS types. TPM
      concentrations were between 0.6 and 8.7 micrograms/liter and thus up to 100-fold
      above the maximum of average concentrations of respiratory suspended particles
      reported for environmental tobacco smoke. Slight reserve cell hyperplasia in the
      anterior part of the nose as well as hyperplastic and metaplastic epithelial
      changes in the larynx were the only observed dose-dependent findings. The
      metabolism of benzo(a)-pyrene--as a proxy for polycyclic aromatic hydrocarbon
      metabolism--was induced in the nasal respiratory epithelium and in the lungs
      while no effect was seen in the nasal olfactory epithelium. The lowest-observed
      effect level was 6 ppm CO or 0.6 microgram TPM/liter. Most of the effects seen
      were less expressed in RASS-than in FSS-exposed rats when compared on the basis
      of the CO concentrations. When compared on the basis of TPM, these effects were
      equally pronounced for both SS types, suggesting a major role of particulate
      matter-associated compounds. All findings reverted to sham control levels
      following a 42-day postinhalation period.

PMID- 9520346
TI  - Uranyl nitrate: 28-day and 91-day toxicity studies in the Sprague-Dawley rat.
AB  - Although uranium (U) is a classic experimental nephrotoxin, there are few data on
      its potential long-term chemical toxicity. These studies were undertaken to
      derive a no-observed-adverse-effect level (NOAEL) in male and female Sprague
      Dawley rats following 91-day exposure to uranium (as uranyl nitrate hexahydrate,
      UN) in drinking water. Following a 28-day range-finding study, five groups of 15
      male and 15 female weanling rats were exposed for 91 days to UN in drinking water
      (0.96, 4.8, 24, 120, or 600 mg UN/L). A control group was given tap water (<
      0.001 mg U/L). Daily clinical observations were recorded. Following the study,
      animals were euthanized and exsanguinated, and multiple hematological and
      biochemical parameters were determined. Necropsies were conducted, and multiple
      tissues were sampled for histopathological examination. The hematological and
      biochemical parameters were not affected in a significant exposure-related
      manner. Although there were qualitative and slight quantitative differences
      between males and females, histopathological lesions were observed in the kidney
      and liver, in both males and females, in all groups including the lowest exposure
      groups. Renal lesions of tubules (apical nuclear displacement and vesiculation,
      cytoplasmic vacuolation, and dilation), glomeruli (capsular sclerosis), and
      interstitium (reticulin sclerosis and lymphoid cuffing) were observed in the
      lowest exposure groups. A NOAEL was not achieved in this study, since adverse
      renal lesions were seen in the lowest exposed groups. A lowest-observed-adverse
      effect level of 0.96 mg UN/L drinking water can be reported for both the male and
      the female rats (average dose equivalent 0.06 and 0.09 mg U/kg body wt/day,
      respectively).

PMID- 9520348
TI  - Uranyl nitrate: 91-day exposure and recovery studies in the male New Zealand
      white rabbit.
AB  - This study was undertaken to examine the reversibility of renal injury in the
      male New Zealand White rabbit subsequent to a 91-day exposure to uranyl nitrate
      (UN) in drinking water, followed by various recovery periods. Specific pathogen
      free (SPF) animals were exposed for 91 days to UN in their drinking water (24 or
      600 mg UN/L). Control groups were given municipal tap water (< 0.001 mg U/L).
      Regular clinical observations were recorded, and urine was collected
      periodically. Recovery periods between the last UN exposure and termination were
      0, 8, 14, 45, or 91 days. Following the study, all animals were anesthetized and
      terminated by exsanguination, and multiple hematological and biochemical
      parameters were determined. Necropsies were conducted, and histopathological
      examination was performed. Exposure-related histopathological changes were
      observed only at much higher doses than in our previous male rabbit study where
      non-SPF-free animals had been used. Minor increases in kidney to body weight
      ratios were observed in the high-dose groups following exposure and early
      recovery. Renal tubular injury with degenerative nuclear changes, cytoplasmic
      vacuolation, and tubular dilation was seen in the high-dose group, without
      consistent resolution even after 91 days recovery. Animals ingested approximately
      33% more uranium per day in this study than did males in a comparable dose group
      in the previous study, yet their kidney tissue uranium residues were 30% lower.
      These results suggest that SPF rabbits are less sensitive to uranyl injury than
      the non-SPF animals. The lowest-observed-adverse-effect level is estimated to lie
      at or below 24 mg UN/L.

PMID- 9520349
TI  - Toxicologists: have we been honest with the public?

PMID- 9520347
TI  - Uranyl nitrate: 91-day toxicity studies in the New Zealand white rabbit.
AB  - These studies were undertaken to derive a lowest-observed-adverse-effect level
      (LOAEL) in the New Zealand White rabbit following a 91-day exposure to uranium
      (U, as uranyl nitrate hexahydrate, UN) in drinking water. Males were exposed for
      91 days to UN in their drinking water (0.96, 4.8, 24, 120, or 600 mg UN/L).
      Subsequently, females were similarly exposed for 91 days (4.8, 24, or 600 mg
      UN/L). Control groups were given tap water (< 0.001 mg U/L). Regular observations
      were recorded, and urine was collected periodically. Four males showed evidence
      of Pasteurella multocida infection and were excluded from the study. Following
      the study, all animals were euthanized, and multiple hematological and
      biochemical parameters were determined. Necropsies were conducted, and
      histopathological examination was performed. The hematological and biochemical
      parameters were not affected in a significant exposure-related manner. Dose
      dependent differences consisted of histopathological changes limited primarily to
      kidney. Changes in renal tubules were characteristic of uranium toxicity. Based
      on changes in the tubular nuclei, the 91-day LOAEL for males in this study is
      0.96 mg UN/L drinking water. The females drank 65% more water than the males, yet
      appeared to be less affected by the exposure regimen, although they also
      developed significant tubular nuclear changes in their lowest exposure group,
      deriving a LOAEL of 4.8 mg UN/L. Tissue uranium residue studies suggested that
      pharmacokinetic parameters for the males and females differ, possibly accounting
      for the difference in observed sensitivity to UN. An adverse effect of P.
      multocida infection cannot be excluded.

PMID- 9520350
TI  - Apoptosis, necrosis, or oncosis: what is your diagnosis? A report from the Cell
      Death Nomenclature Committee of the Society of Toxicologic Pathologists.

PMID- 9520351
TI  - Acute intoxication with trichloroethene: clinical symptoms, toxicokinetics,
      metabolism, and development of biochemical parameters for renal damage.
AB  - The present study reports on a 17-year-old male who ingested approximately 70 ml
      trichloroethene (TRI) in a suicide attempt. The patient developed fever, tremor,
      general motor restlessness, and sinus tachycardia and lost consciousness 5 h
      after poisoning. After 5 days of intubation under narcosis with forced
      hyperventilation and diuresis he regained consciousness. During this period blood
      and urine were collected and TRI and its metabolites were quantified. The highest
      concentration of TRI in blood was detected 13 h after ingestion. Trichloroethanol
      and trichloroacetic acid, metabolites of the cytochrome P450-mediated pathway,
      and N-acetyl-S-(1, 2-dichlorovinyl)-l-cysteine and N-acetyl-S-(2, 2
      dichlorovinyl)-l-cysteine from the glutathione-dependent pathway of TRI were
      quantified in urine samples. Besides these known metabolites in humans,
      chloroacetic acid and dichloroacetic acid were identified for the first time in
      urine of a human exposed to TRI. Although the patient exhibited normal levels of
      glucose and total protein in urine, excretion of alpha1- and beta2-microglobulin
      as well as beta-NAG was significantly increased. In addition to these typical
      markers of selective tubule damage, analysis of the urinary protein pattern by
      SDS-PAGE revealed increased excretion of several low-molecular-mass proteins
      between 10,000 and 50,000 Da, clearly indicating tubular damage. Based on the
      elucidated glutathione-dependent mechanism for the nephrotoxicity of TRI,
      activation of the formed S-conjugates by beta-lyases to reactive intermediates
      may account for the observed renal effects after a single, high dose of TRI.

PMID- 9520352
TI  - Disposition of butadiene epoxides in Sprague-Dawley rats following exposures to
      8000 ppm 1,3-butadiene: comparisons with tissue epoxide concentrations following
      low-level exposures.
AB  - 1,3-Butadiene (BD), a compound used extensively in the rubber industry, is weakly
      carcinogenic in Sprague-Dawley rats after chronic exposures to concentrations of
      1000 and 8000 ppm. Conversely, in B6C3F1 mice, tumors occur after chronic
      exposures to concentrations as low as 6.25 ppm. Previously, we have shown that
      tissue concentrations of the mutagenic BD metabolites, butadiene monoepoxide
      (BDO) and butadiene diepoxide (BDO2), are present in greater concentrations in
      mice than in rats following acute exposures to low levels (100 ppm or less). This
      disparity was particularly significant for the diepoxide. We hypothesized that if
      these epoxides are involved in the carcinogenic response of BD, then they will
      also be present in rat tissues at relatively high concentrations following
      exposures to 8000 ppm BD. In the present study, concentrations of the BD
      epoxides, BDO and BDO2, were determined in blood of female Sprague-Dawley rats
      following a single 6-h exposure and 10 repeated exposures to a target
      concentration of 8000 ppm BD. Concentrations of these epoxides were also
      determined in a number of other tissues, including the primary rat target organ
      mammary gland-following 10 repeated exposures. Blood concentrations of BDO were
      4030 pmol/g +/- 191 following a 6-h exposure and were 18% lower following the 10
      day exposure. Blood concentrations of BDO2, following the 8000 ppm exposures,
      were very similar to those previously observed after exposures to 62.5 ppm BD (11
      +/- 1 and 17 +/- 1 pmol/g following exposures of 6h and 6h/day for 10 days,
      respectively.) Concentrations of BDO ranged from 740 +/- 110 (femur) to 8990 +/-
      1150 (fat) pmol/g tissue. Concentrations of BDO2 were similar among eight tissues
      analyzed, ranging from 5 +/- 1 (femur) to 17 +/- 3 (heart) pmol/g tissue. Tissue
      concentrations of butadiene monoepoxide were increased by 17- to 50-fold in
      tissues from rats exposed by inhalation to 8000 ppm BD as compared to tissues
      from rats exposed to 62.5 ppm BD. Based on earlier studies at our institute the
      internal dose of BD increases approximately 14-fold in the 8000 ppm-exposed rats
      compared to rats exposed to 62.5 ppm BD. Concentrations of butadiene diepoxide in
      rat tissues following an exposure to 8000 ppm BD were similar to those observed
      in rat tissues following exposures to 62.5 ppm BD. This study shows that pathways
      responsible for the accumulation of BDO2 in rats are saturated following low
      level BD exposures. This suggests that the primary determinant of BD
      tumorigenicity in rats is not butadiene diepoxide. The high levels of BDO
      observed in rat mammary tissue suggest that this metabolite may be a more
      important determinant of BD carcinogenesis in the rat.

PMID- 9520353
TI  - Prevention of maternal and developmental toxicity in rats via dietary inclusion
      of common aflatoxin sorbents: potential for hidden risks.
AB  - In earlier work, we have reported that a phyllosilicate clay (HSCAS or NovaSil)
      can tightly and selectively bind the aflatoxins in vitro and in vivo. Since then,
      a variety of untested clay and zeolitic minerals have been added to poultry and
      livestock feeds as potential "aflatoxin binders." However, the efficacy and
      safety of these products have not been determined. A common zeolite that has been
      frequently added to animal feed is clinoptilolite. Our objectives in this study
      were twofold: (1) to utilize the pregnant rat as an in vivo model to compare the
      potential of HSCAS and clinoptilolite to prevent the developmental toxicity of
      aflatoxin B1 (AfB1), and (2) to determine the effect of these two sorbents on the
      metabolism and bioavailability of AfB1. Clay and zeolitic minerals (HSCAS or
      clinoptilolite) were added to the diet at a level of 0.5% (w/w) and fed to
      pregnant Sprague-Dawley rats throughout pregnancy (i.e., day 0 to 20). Treatment
      groups (HSCAS or clinoptilolite) alone and in combination with AfB1 were exposed
      to sorbents in the feed as well as by gavage. Untreated and AfB1 control animals
      were fed the basal diet without added sorbent. Between gestation days 6 and 13,
      animals maintained on diets containing sorbent were gavaged with corn oil in
      combination with an amount of the respective sorbent equivalent to 0.5% of the
      estimated maximum daily intake of feed. Animals receiving AfB1 were dosed orally
      (between days 6 and 13) with AfB1 (2 mg/kg body wt) either alone or concomitantly
      with a similar quantity of the respective sorbent. Evaluations of toxicity were
      performed on day 20. These included: maternal (mortality, body weights, feed
      intake, and litter weights), developmental (embryonic resorptions and fetal body
      weights), and histological (maternal livers and kidneys). Sorbents alone were not
      toxic; AfB1 alone and with clinoptilolite resulted in significant maternal and
      developmental toxicity. Animals treated with HSCAS (plus AfB1) were comparable to
      controls. Importantly, clinoptilolite (plus AfB1) resulted in severe maternal
      liver lesions (more severe than AfB1 alone), suggesting that this zeolite may
      interact with dietary components that modulate aflatoxicosis. In metabolism
      studies, adult male Sprague-Dawley rats, maintained on diets containing 0.5%
      (w/w) HSCAS or clinoptilolite, were dosed orally with 2.0 mg AfB1/kg body wt. The
      concentration of the major urinary metabolite (AfM1) was considerably decreased
      in the presence of HSCAS. These results suggest that the mechanism of protection
      of AfB1-induced maternal and developmental toxicities in the rat may involve
      adsorption and reduction of AfB1 bioavailability in vivo. Importantly, this study
      demonstrates the potential for significant hidden risks associated with the
      inclusion of nonselective aflatoxin binders in feeds. Aflatoxin sorbents should
      be rigorously tested individually and thoroughly characterized in vivo, paying
      particular attention to their effectiveness and safety in sensitive animal models
      and their potential for deleterious interactions.

PMID- 9520354
TI  - Carcinogenesis studies of tetrahydrofuran vapors in rats and mice.
AB  - Tetrahydrofuran (THF) is a widely used industrial solvent and was selected for
      carcinogenesis studies by the National Toxicology Program (NTP) because of its
      potential for widespread occupational exposure in humans and a lack of
      information on animal toxicity and carcinogenicity. Groups of 50 male and 50
      female F344/N rats and B6C3F1 mice were exposed to 0, 200, 600, or 1800 ppm THF
      by inhalation, 6 h per day, 5 days per week, for 105 weeks. Survival and mean
      body weights of male and female rats exposed to THF were comparable to that of
      the controls. No clinical findings or nonneoplastic lesions related to THF
      exposure were observed in male or female rats. The incidences of renal tubule
      epithelial adenoma or carcinoma (combined) in exposed male rats occurred with a
      positive trend, and in males exposed to 600 and 1800 ppm exceeded the historical
      range for controls in 2-year NTP inhalation studies. There were no other
      neoplastic lesions related to THF exposure observed in male or female rats. After
      week 36, the survival of male mice exposed to 1800 ppm was significantly lower
      than that of the controls. Mean body weights of male and female mice exposed to
      THF were similar to those of the controls throughout the study. Male mice exposed
      to 1800 ppm were observed in a state of narcosis during and up to 1 h after the
      exposure periods. Nonneoplastic lesions related to THF exposure were not observed
      in male or female mice. The neoplastic lesions related to THF exposure were seen
      in female mice only. In female mice exposed to 1800 ppm, the incidences of
      hepatocellular neoplasms were significantly greater than those in the controls.
      In conclusion, there was some evidence of carcinogenic activity of THF in male
      F344/N rats due to increased incidences of adenoma or carcinoma (combined) of the
      kidney at the 600 and 1800 ppm exposure levels. There was clear evidence of
      carcinogenic activity in female B6C3F1 mice based on increased incidences of
      hepatocellular neoplasms at the 1800 ppm exposure level. THF was not carcinogenic
      in female rats or male mice exposed at 200, 600, or 1800 ppm.

PMID- 9520355
TI  - Assessing the predictiveness of the Syrian hamster embryo cell transformation
      assay for determining the rodent carcinogenic potential of single ring
      aromatic/nitroaromatic amine compounds.
AB  - The pH 6.7 Syrian hamster embryo (SHE) cell transformation assay was used to test
      the morphological transformation potential of 5 rodent carcinogenic single ring
      aromatic/nitroaromatic amine compounds: 2-amino-4-nitrotoluene, 2,4
      diaminotoluene, 2,4-dinitrotoluene, o-anisidine hydrochloride, and o-toluidine;
      and 5 noncarcinogenic single ring aromatic/nitroaromatic amine compounds: 2,6
      diaminotoluene, 2,4-dimethoxyaniline hydrochloride, 4-nitro-o-phenylenediamine, p
      phenylenediamine dihydrochloride, and HC Blue No. 2. All 5 rodent carcinogens
      produced significant morphological transformation in a dose-responsive manner.
      None of the 5 noncarcinogens yielded significant transformation at any of the
      doses tested. Therefore, the concordance between the pH 6.7 SHE cell
      transformation assay and rodent carcinogenicity for these 10 single ring
      aromatic/nitroaromatic amine compounds is 100%. In contrast, the concordance
      between the standard SHE cell transformation assay and rodent carcinogenicity for
      13 single ring aromatic/nitroaromatic amine compounds was 62%. For 5
      aromatic/nitroaromatic amine compounds which were tested in both standard and pH
      6.7 SHE cell transformation assays (i.e., a subset of the above two databases),
      the concordance between the standard SHE cell transformation assay and the rodent
      bioassay was 40%, while the concordance between the pH 6.7 SHE cell
      transformation assay and the rodent bioassay was 100%. This relatively high
      concordance between the pH 6.7 SHE cell transformation assay and rodent bioassay
      results demonstrates the utility of the pH 6.7 SHE cell transformation assay for
      predicting the rodent carcinogenic potential of single ring
      aromatic/nitroaromatic amine compounds.

PMID- 9520356
TI  - An evaluation of the novel selective estrogen receptor modulator, idoxifene, for
      effects on reproduction in rats and rabbits.
AB  - Idoxifene, a tissue-specific selective estrogen receptor modulator, was evaluated
      in male and female rats and female rabbits after oral administration for effects
      on fertility and/or embryo-fetal development. In all studies, adult toxicity was
      evident at doses >/=0.03 mg/kg/day in rats and >/=0.1 mg/kg/day in rabbits as
      evidenced by decreased body weight and/or food consumption. In the male fertility
      study, rats were treated with 0.003, 0.3, or 3.0 mg/kg/day for 64 to 68 days.
      Doses >/=0.3 mg/kg/day decreased seminal vesicle and prostate weights and
      impaired posttesticular sperm development, resulting in decreased epididymal
      sperm count and weight, but did not affect male fertility. In the female
      fertility study, rats were treated for 2 weeks prior to mating until insemination
      with 0.003, 0.03, or 3.0 mg/kg/day. Disrupted estrous cycles, impaired fertility,
      increased preimplantation loss, and increased vaginal fluid at necropsy were
      evident at >/=0.03 mg/kg/day. In the early embryonic development study, pregnant
      female rats were treated from days 0 to 6 postcoitus (pc) with 0.003, 0.03, or
      3.0 mg/kg/day idoxifene. Partial or complete preimplantation loss was seen at
      0.03 and 3.0 mg/kg/day, respectively. In the embryo-fetal development study,
      pregnant rats were treated from days 6 to 17 pc with 0.003, 0.03, or 3.0
      mg/kg/day. At 3.0 mg/kg/day there was maternal lethality, excess vaginal fluid,
      embryo-fetal death, generalized fetal edema, and developmental delays. Excess
      vaginal fluid but no fetal effects were seen at 0.03 mg/kg/day. There were no
      treatment-related effects at 0.003 mg/kg/day in any rat reproduction study
      performed. In the rabbit embryo-fetal development study, pregnant New Zealand
      White rabbits were treated from days 6 to 20 pc with 0.01, 0.1, or 1.0 mg/kg/day
      idoxifene. At 1.0 mg/kg/day there was maternal lethality, vaginal or uterine
      bleeding, abortion/premature deliveries, and embryolethality. Vaginal or uterine
      bleeding was seen at 0.1 mg/kg/day. No treatment-related effects were observed at
      0.01 mg/kg/day. Although systemic toxicity was evident in all the studies, the
      effects of idoxifene on rat and rabbit reproduction were considered to be due to
      the pharmacological activity of the compound.

PMID- 9520357
TI  - Cardiac arrhythmia induction after exposure to residual oil fly ash particles in
      a rodent model of pulmonary hypertension.
AB  - Recent epidemiological studies have reported a positive association between
      exposure to ambient concentrations of particulate matter (PM) and the incidence
      of cardiopulmonary-related morbidity and mortality. The present study examined
      the effects of fugitive residual oil fly ash (ROFA) PM on cardiac arrhythmia
      induction in healthy and cardiopulmonary-compromised rodents. Male Sprague-Dawley
      rats were implanted with radiotelemetry transmitters capable of monitoring the
      electrocardiogram and were subjected to one of two treatment regimens. Rats in
      the first treatment regimen (n = 16) served as normal control animals whereas
      rats in the second treatment regimen (n = 16) were injected with monocrotaline
      (MCT, 60 mg/kg, ip) to induce pulmonary vascular inflammation and hypertension
      and served as a model of cardiopulmonary disease. Rats within each treatment
      regimen were equally divided into four dose groups (0.0, 0.25, 1.0, 2.5 mg ROFA),
      instilled intratracheally, and monitored for 96 h. In the animals in the first
      treatment regimen, ROFA instillation caused dose-related increases in the
      incidence and duration of serious arrhythmic events that appeared to be
      associated with impaired atrioventricular conduction and myocardial hypoxia.
      There were no lethalities in the normal animals following ROFA instillation. The
      frequency and severity of arrhythmias were greatly exacerbated in the MCT-treated
      animals in the second treatment regimen and were accompanied by one, three, and
      two deaths in the low-, medium-, and high-dose groups, respectively. The results
      of the present study demonstrate substantial cardiac effects in normal and
      compromised rats after exposure to ROFA PM and implicate both conductive and
      hypoxemic arrhythmogenic mechanisms in the observed cardiac-related lethalities.
      These results support previous epidemiological studies that suggest a link
      between preexisting cardiopulmonary disease and potentiation of adverse health
      effects following exposure to anthropogenic particulates.

PMID- 9520358
TI  - Effect of ozone exposure on alveolar macrophage-mediated immunosuppressive
      activity in rats.
AB  - Ozone (O3), a major component of photochemical air pollution, is a strong
      oxidizing agent and highly toxic. Resident alveolar macrophages (AM) play an
      important immunomodulatory role in the lung via suppression of lymphocyte
      proliferation, thus limiting the magnitude and duration of local immune
      responses. Nitric oxide (NO) plays a crucial role in the immunosuppressive
      activity of AM. However, during immunoinflammatory responses, microenvironmental
      changes within the alveoli inhibit this AM function, permitting full expression
      of local T-cell-mediated immune responses. We hypothesize that similar changes in
      AM function may occur during inflammation induced by exposure to inorganic air
      pollutants, such as O3. In order to test this hypothesis, in the present study,
      we investigated (1) whether O3 exposure of rats might affect the
      immunosuppressive activity and NO production of bronchoalveolar lavage cells (BAL
      cells) and (2) whether changes in the microenvironment of the alveoli induced by
      O3 exposure can affect the immunosuppressive activity and NO production of AM. AM
      mediated immunosuppressive activity was measured as inhibition of concanavalin A
      (Con A)-induced proliferation of lymph node cells (LNC). Bronchoalveolar lavage
      was used to sample the alveolar microenvironment, and the resulting fluid (BALF)
      was tested for capacity to modulate AM activity in the cultures. BALF and BAL
      cells from rats exposed to 1 ppm O3 or filtered air for 3 days were used. The
      present results demonstrate that BAL cells isolated from O3-exposed rats
      suppressed Con A-induced LNC proliferation and produced NO in the same manner as
      BAL cells (AM) from air-exposed rats. AM-mediated suppressive activity of LNC
      proliferation and NO production were markedly inhibited by BALF from O3-exposed
      but not from air-exposed rats. These results suggested that AM-mediated
      immunosuppressive activity in vivo may be inhibited by the O3-induced release of
      soluble factors which inhibit NO production by AM.

PMID- 9520361
TI  - Recent excitement regarding metallothionein.

PMID- 9520359
TI  - N-acetylcysteine as an antidote in methylmercury poisoning.
AB  - Methylmercury is a ubiquitous environmental pollutant and potent neurotoxin.
      Treatment of methylmercury poisoning relies almost exclusively on the use of
      chelating agents to accelerate excretion of the metal. The present study
      demonstrates that oral administration of N-acetylcysteine (NAC), a widely
      available and largely nontoxic amino acid derivative, produces a profound
      acceleration of urinary methylmercury excretion in mice. Mice that received NAC
      in the drinking water (10 mg/ml) starting at 48 hr after methylmercury
      administration excreted from 47 to 54% of the 203Hg in urine over the subsequent
      48 hr, as compared to 4-10% excretion in control animals. When NAC-containing
      water was given from the time of methylmercury administration, it was even more
      effective at enhancing urinary methylmercury excretion and at lowering tissue
      mercury levels. In contrast, excretion of inorganic mercury was not affected by
      oral NAC administration. The ability of NAC to enhance methylmercury excretion
      when given orally, its relatively low toxicity, and is wide availability in the
      clinical setting indicate that it may be an ideal therapeutic agent for use in
      methylmercury poisoning.

PMID- 9520360
TI  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin plasma levels in Seveso 20 years after the
      accident.
AB  - In 1976, near Seveso, Italy, an industrial accident caused the release of large
      quantities of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) into the atmosphere,
      resulting in the highest levels of the toxicant ever recorded in humans. The
      contaminated area was divided into three zones (A, B, R) corresponding to
      decreasing TCDD levels in soil, and cohort including all residents was
      enumerated. The population of the surrounding noncontaminated area (non-ABR) was
      chosen as referent population. Two decades after the accident. plasma TCDD levels
      were measured in 62 subjects randomly sampled from the highest exposed zones (A
      and B) and 59 subjects from non-ABR, frequency matched for age, gender, and
      cigarette smoking status. Subjects living in the exposed areas have persistently
      elevated plasma TCDD levels (range = 1.2-89.9 ppt; geometric mean = 53.2 and 11.0
      ppt for Zone A and Zone B, respectively). Levels significantly decrease by
      distance from the accident site (p = 0.0001), down to general population values
      (4.9 ppt) in non-ABR, thus validating the original zone classification based on
      environmental measurements. Women have higher TCDD levels than men in the entire
      study area (p = 0.0003 in Zone B; p = 0.007 in non-ABR). This gender difference
      persists after adjustment for location within the zone, consumption of meat
      derived from locally raised animals, age, body mass index, and smoking. There is
      no evidence for a gender difference in exposure, so variation in metabolism or
      elimination due to body fat or hormone-related factors may explain this finding.
      Elevated TCDD levels in women may contribute to adverse reproductive,
      developmental, and cancer outcomes.

PMID- 9520362
TI  - Depudecin makes a debut.

PMID- 9520365
TI  - Visual scenes and cortical neurons: what you see is what you get.

PMID- 9520363
TI  - Assaying for peptides in individual Aplysia neurons with mass spectrometry.

PMID- 9520364
TI  - To muster a cluster: anchoring neurotransmitter receptors at synapses.

PMID- 9520366
TI  - Is sex better? Parasites say "no".

PMID- 9520367
TI  - An important step forward in the genetic manipulation of mosquito vectors of
      human disease.

PMID- 9520368
TI  - A gravitational diffusion model without dark matter.
AB  - In this model, without dark matter, the flat rotation curves of galaxies and the
      mass-to-light ratios of clusters of galaxies are described quantitatively. The
      hypothesis is that the agent of gravitational force is propagated as if it were
      scattered with a mean free path of approximately 5 kiloparsecs. As a result, the
      force between moderately distant masses, separated by more than the mean free
      path, diminishes as the inverse first power of the distance, following diffusion
      equations, and describes the flat rotation curves of galaxies. The force between
      masses separated by <1 kiloparsec diminishes as the inverse square of distance.
      The excess gravitational force (ratio of 1/r:1/r2) increases with the scale of
      structures from galaxies to clusters of galaxies. However, there is reduced force
      at great distances because of the approximately 12 billion years that has been
      available for diffusion to occur. This model with a mean free path of
      approximately 5 kiloparsecs predicts a maximum excess force of a few hundredfold
      for objects the size of galactic clusters a few megaparsecs in size. With only a
      single free parameter, the predicted curve for excess gravitational force vs.
      size of structures fits reasonably well with observations from those for dwarf
      galaxies through galactic clusters. Under the diffusion model, no matter is
      proposed in addition to the observed baryons plus radiation and thus the proposed
      density of the universe is only a few percent of that required for closure.

PMID- 9520369
TI  - Depudecin induces morphological reversion of transformed fibroblasts via the
      inhibition of histone deacetylase.
AB  - Depudecin is a fungal metabolite that reverts the rounded phenotype of NIH 3T3
      fibroblasts transformed with v-ras and v-src oncogenes to the flattened phenotype
      of the nontransformed parental cells. The mechanism of detransformation induced
      by this agent had not been determined. Here, we demonstrate that depudecin
      inhibits histone deacetylase (HDAC) activity effectively both in vivo and in
      vitro. Depudecin induces similar morphological reversion in v-ras transformed NIH
      3T3 cells as do other naturally occurring HDAC inhibitors such as trichostatin A
      or trapoxin. It competitively inhibits the binding of [3H]trapoxin in vitro and
      the nuclear binding of a trapoxin-coumarin fluorophore in vivo, suggesting that
      depudecin shares a nuclear binding protein and site on that protein with
      trapoxin. Furthermore, depudecin induces hyperacetylation of histones in a dose
      dependent manner and at concentrations comparable with that required for
      detransformation. An in vitro histone deacetylase assay, using purified
      recombinant HDAC1, reveals that depudecin inhibits 50% of the enzyme activity at
      a concentration of 4.7 microM. These results demonstrate that depudecin is a
      novel HDAC inhibitor and suggest that its ability to induce morphological
      reversion of transformed cells is the result of its HDAC inhibitory activity.

PMID- 9520371
TI  - Atmospheric weathering and silica-coated feldspar: analogy with zeolite molecular
      sieves, granite weathering, soil formation, ornamental slabs, and ceramics.
AB  - Feldspar surfaces respond to chemical, biological, and mechanical weathering. The
      simplest termination is hydroxyl (OH), which interacts with any adsorption layer.
      Acid leaching of alkalis and aluminum generated a silica-rich, nanometers-thick
      skin on certain feldspars. Natural K, Na-feldspars develop fragile surfaces as
      etch pits expand into micrometer honeycombs, possibly colonized by lichens. Most
      crystals have various irregular coats. Based on surface-catalytic processes in
      molecular sieve zeolites, I proposed that some natural feldspars lose weakly
      bonded Al-OH (aluminol) to yield surfaces terminated by strongly bonded Si-OH
      (silanol). This might explain why some old feldspar-bearing rocks weather slower
      than predicted from brief laboratory dissolution. Lack of an Al-OH infrared
      frequency from a feldspar surface is consistent with such a silanol-dominated
      surface. Raman spectra of altered patches on acid-leached albite correspond with
      amorphous silica rather than hydroxylated silica-feldspar, but natural feldspar
      may respond differently. The crystal structure of H-exchanged feldspar provides
      atomic positions for computer modeling of complex ideas for silica-terminated
      feldspar surfaces. Natural weathering also depends on swings of temperature and
      hydration, plus transport of particles, molecules, and ionic complexes by rain
      and wind. Soil formation might be enhanced by crushing granitic outcrops to
      generate new Al-rich surfaces favorable for chemical and biological weathering.
      Ornamental slabs used by architects and monumental masons might last longer by
      minimizing mechanical abrasion during sawing and polishing and by silicifying the
      surface. Silica-terminated feldspar might be a promising ceramic surface.

PMID- 9520370
TI  - Creatine kinase: essential arginine residues at the nucleotide binding site
      identified by chemical modification and high-resolution tandem mass spectrometry.
AB  - Phenylglyoxal is an arginine-specific reagent that inactivates creatine kinase
      (CK). Previous results suggest that modification of the dimeric enzyme at a
      single arginine residue per subunit causes complete inactivation accompanied by
      the loss of nucleotide binding; the actual site of modification was not
      identified. Here, high-resolution tandem mass spectrometry (MS/MS) was used to
      identify three phenylglyoxal-modified Arg residues in monomeric rabbit muscle CK.
      Electrospray ionizaton Fourier-transform MS of the phenylglyoxal-modified CK that
      had lost approximately 80% activity identified three species: unmodified, once
      modified (+116 Da), and twice-modified (+232 Da) enzyme in a ratio of
      approximately 1:4:1. MS/MS restricts the derivatized sites to P122-P212 and P283
      V332, whereas MS of Lys-C digestions revealed two modified peptides, A266-K297
      and G116-K137. The only Arg in A266-K297 is Arg-291 (invariant), whereas MS/MS of
      modified G116-K137 shows that two of the three sites Arg-129, Arg-131, or Arg-134
      (all invariant) can contain the modification. The recently reported x-ray crystal
      structure for the octameric chicken mitochondrial CK indicates that its
      nucleotide triphosphate-binding site indeed contains the equivalent of R291,
      R129, and R131 reported here to be at the active site of rabbit muscle CK.

PMID- 9520373
TI  - The hochschild cohomology problem for von neumann algebras.
AB  - In 1967, when Kadison and Ringrose began the development of continuous cohomology
      theory for operator algebras, they conjectured that the cohomology groups Hn(M,
      M), n >/= 1, for a von Neumann algebra M, should all be zero. This conjecture,
      which has important structural implications for von Neumann algebras, has been
      solved affirmatively in the type I, IIinfinity, and III cases, leaving open only
      the type II1 case. In this paper, we describe a positive solution when M is type
      II1 and has a Cartan subalgebra and a separable predual.

PMID- 9520372
TI  - Biochemical evolution. I. Polymerization On internal, organophilic silica
      surfaces of dealuminated zeolites and feldspars.
AB  - Catalysis at mineral surfaces might generate replicating biopolymers from simple
      chemicals supplied by meteorites, volcanic gases, and photochemical gas
      reactions. Many ideas are implausible in detail because the proposed mineral
      surfaces strongly prefer water and other ionic species to organic ones. The
      molecular sieve silicalite (Union Carbide; = Al-free Mobil ZSM-5 zeolite) has a
      three-dimensional, 10-ring channel system whose electrically neutral Si-O surface
      strongly adsorbs organic species over water. Three -O-Si tetrahedral bonds lie in
      the surface, and the fourth Si-O points inwards. In contrast, the outward Si-OH
      of simple quartz and feldspar crystals generates their ionic organophobicity. The
      ZSM-5-type zeolite mutinaite occurs in Antarctica with boggsite and tschernichite
      (Al-analog of Mobil Beta). Archean mutinaite might have become de-aluminated
      toward silicalite during hot/cold/wet/dry cycles. Catalytic activity of
      silicalite increases linearly with Al-OH substitution for Si, and Al atoms tend
      to avoid each other. Adjacent organophilic and catalytic Al-OH regions in
      nanometer channels might have scavenged organic species for catalytic assembly
      into specific polymers protected from prompt photochemical destruction. Polymer
      migration along weathered silicic surfaces of micrometer-wide channels of
      feldspars might have led to assembly of replicating catalytic biomolecules and
      perhaps primitive cellular organisms. Silica-rich volcanic glasses should have
      been abundant on the early Earth, ready for crystallization into zeolites and
      feldspars, as in present continental basins. Abundant chert from weakly
      metamorphosed Archaean rocks might retain microscopic clues to the proposed
      mineral adsorbent/catalysts. Other framework silicas are possible, including ones
      with laevo/dextro one-dimensional channels. Organic molecules, transition-metal
      ions, and P occur inside modern feldspars.

PMID- 9520374
TI  - Anticancer action of cube insecticide: correlation for rotenoid constituents
      between inhibition of NADH:ubiquinone oxidoreductase and induced ornithine
      decarboxylase activities.
AB  - Rotenone and rotenoid-containing botanicals, important insecticides and fish
      poisons, are reported to have anticancer activity in rats and mice. The toxic
      action of rotenone is attributed to inhibition of NADH:ubiquinone oxidoreductase
      activity and the purported cancer chemopreventive effect of deguelin analogs has
      been associated with inhibition of phorbol ester-induced ornithine decarboxylase
      (ODC) activity. This study defines a possible relationship between these two
      types of activity important in evaluating the toxicology of rotenoid pesticides
      and the suitability of the anticancer model. Fractionation of cube resin (the
      commercial rotenoid pesticide) establishes that the activity in both assays is
      due primarily to rotenone (IC50 = 0.8-4 nM), secondarily to deguelin, and in
      small part to rotenolone and tephrosin. In addition, the potency of 29 rotenoids
      from cube insecticide for inhibiting NADH:ubiquinone oxidoreductase in vitro
      assayed with bovine heart electron transport particles satisfactorily predicts
      their potency in vivo in the induced ODC assay using noncytotoxic rotenoid
      concentrations with cultured MCF-7 human breast cancer cells (r = 0.86). Clearly
      the molecular features of rotenoids essential for inhibiting NADH:ubiquinone
      oxidoreductase are similar to those for blocking ODC induction. This apparent
      correlation extends to 11 flavonoids and stilbenoids from cube resin (r = 0.98)
      and genistein and resveratrol except for lower potency and less selectivity than
      the rotenoids relative to cytotoxicity. These findings on cube insecticide
      constituents and our earlier study comparing rotenone and pyridaben miticide
      indicate that inhibition of NADH:ubiquinone oxidoreductase activity lowers the
      level of induced ODC activity leading to the antiproliferative effect and
      anticancer action.

PMID- 9520375
TI  - Plasmodium gallinaceum preferentially invades vesicular ATPase-expressing cells
      in Aedes aegypti midgut.
AB  - Penetration of the mosquito midgut epithelium is obligatory for the further
      development of Plasmodium parasites. Therefore, blocking the parasite from
      invading the midgut wall disrupts the transmission of malaria. Despite such a
      pivotal role in malaria transmission, the cellular and molecular interactions
      that occur during the invasion are not understood. Here, we demonstrate that the
      ookinetes of Plasmodium gallinaceum, which is related closely to the human
      malaria parasite Plasmodium falciparum, selectively invade a cell type in the
      Aedes aegypti midgut. These cells, unlike the majority of the cells in the
      midgut, do not stain with a basophilic dye (toluidine blue) and are less
      osmiophilic. In addition, they contain minimal endoplasmic reticulum, lack
      secretory granules, and have few microvilli. Instead, these cells are highly
      vacuolated and express large amounts of vesicular ATPase. The enzyme is
      associated with the apical plasma membrane, cytoplasmic vesicles, and tubular
      extensions of the basal membrane of the invaded cells. The high cost of
      insecticide use in endemic areas and the emergence of drug resistant malaria
      parasites call for alternative approaches such as modifying the mosquito to block
      the transmission of malaria. One of the targets for such modification is the
      parasite receptor on midgut cells. A step toward the identification of this
      receptor is the realization that malaria parasites invade a special cell type in
      the mosquito midgut.

PMID- 9520376
TI  - High-resolution restriction maps of bacterial artificial chromosomes constructed
      by optical mapping.
AB  - Large insert clone libraries have been the primary resource used for the physical
      mapping of the human genome. Research directions in the genome community now are
      shifting direction from purely mapping to large-scale sequencing, which in turn,
      require new standards to be met by physical maps and large insert libraries.
      Bacterial artificial chromosome libraries offer enormous potential as the chosen
      substrate for both mapping and sequencing studies. Physical mapping, however, has
      come under some scrutiny as being "redundant" in the age of large-scale automated
      sequencing. We report the development and applications of nonelectrophoretic,
      optical approaches for high-resolution mapping of bacterial artificial chromosome
      that offer the potential to complement and thereby advance large-scale sequencing
      projects.

PMID- 9520377
TI  - Linker histone protects linker DNA on only one side of the core particle and in a
      sequence-dependent manner.
AB  - The protection against micrococcal nuclease digestion afforded to chromatosomal
      DNA by the presence of a linker histone (H1(o)) has been quantitatively measured
      in two reconstituted systems. We have used chromatosomes reconstituted at two
      distinct positions on a DNA fragment containing the 5S rRNA gene from Lytechinus
      variegatus and at a specific position on a sequence containing Gal4- and USF
      binding sites. In all cases, we find asymmetric protection, with approximately 20
      bp protected on one side of the core particle and no protection on the other. We
      demonstrated through crosslinking experiments that the result is not due to any
      sliding of the histone core caused by either linker histone addition or
      micrococcal nuclease cleavage. Because the core particle is itself a symmetric
      object, the preferred asymmetric location of a linker histone must be dictated by
      unknown elements in the DNA sequence.

PMID- 9520378
TI  - A single side chain prevents Escherichia coli DNA polymerase I (Klenow fragment)
      from incorporating ribonucleotides.
AB  - Although nucleic acid polymerases from different families show striking
      similarities in structure, they maintain stringent specificity for the sugar
      structure of the incoming nucleoside triphosphate. The Klenow fragment of E. coli
      DNA polymerase I selects its natural substrates, deoxynucleotides, over
      ribonucleotides by several thousand fold. Analysis of mutant Klenow fragment
      derivatives indicates that discrimination is provided by the Glu-710 side chain
      which sterically blocks the 2'-OH of an incoming rNTP. A nearby aromatic side
      chain, at position 762, plays an important role in constraining the nucleotide so
      that the Glu-710 "steric gate" can be fully effective. Even with the E710A
      mutation, which is extremely permissive for addition of a single ribonucleotide
      to a DNA primer, Klenow fragment does not efficiently synthesize pure RNA,
      indicating that additional barriers prevent the incorporation of successive
      ribonucleotides.

PMID- 9520379
TI  - Crystal structure of the catalytic domain of human tumor necrosis factor-alpha
      converting enzyme.
AB  - Tumor necrosis factor-alpha (TNFalpha) is a cytokine that induces protective
      inflammatory reactions and kills tumor cells but also causes severe damage when
      produced in excess, as in rheumatoid arthritis and septic shock. Soluble TNFalpha
      is released from its membrane-bound precursor by a membrane-anchored proteinase,
      recently identified as a multidomain metalloproteinase called TNFalpha-converting
      enzyme or TACE. We have cocrystallized the catalytic domain of TACE with a
      hydroxamic acid inhibitor and have solved its 2.0 A crystal structure. This
      structure reveals a polypeptide fold and a catalytic zinc environment resembling
      that of the snake venom metalloproteinases, identifying TACE as a member of the
      adamalysin/ADAM family. However, a number of large insertion loops generate
      unique surface features. The pro-TNFalpha cleavage site fits to the active site
      of TACE but seems also to be determined by its position relative to the base of
      the compact trimeric TNFalpha cone. The active-site cleft of TACE shares
      properties with the matrix metalloproteinases but exhibits unique features such
      as a deep S3' pocket merging with the S1' specificity pocket below the surface.
      The structure thus opens a different approach toward the design of specific
      synthetic TACE inhibitors, which could act as effective therapeutic agents in
      vivo to modulate TNFalpha-induced pathophysiological effects, and might also help
      to control related shedding processes.

PMID- 9520380
TI  - Crystal structure of MTCP-1: implications for role of TCL-1 and MTCP-1 in T cell
      malignancies.
AB  - Two related oncogenes, TCL-1 and MTCP-1, are overexpressed in T cell
      prolymphocytic leukemias as a result of chromosomal rearrangements that involve
      the translocation of one T cell receptor gene to either chromosome 14q32 or Xq28.
      The crystal structure of human recombinant MTCP-1 protein has been determined at
      2.0 A resolution by using multiwavelength anomalous dispersion data from
      selenomethionine-enriched protein and refined to an R factor of 0.21. MTCP-1
      folds into a compact eight-stranded beta barrel structure with a short helix
      between the fourth and fifth strands. The topology is unique. The structure of
      TCL-1 has been predicted by molecular modeling based on 40% amino acid sequence
      identity with MTCP-1. The identical residues are clustered inside the barrel and
      on the surface at one side of the barrel. The overall structure of MTCP-1
      superficially resembles the structures of proteins in the lipocalin family and
      calycin superfamily. These proteins have diverse functions, including transport
      of retinol, fatty acids, chromophores, pheromones, synthesis of prostaglandin,
      immune modulation, and cell regulation. However, MTCP-1 differs in the topology
      of the beta strands. The structural similarity suggests that MTCP-1 and TCL-1
      form a unique family of beta barrel proteins that is predicted to bind small
      hydrophobic ligands and function in cell regulation.

PMID- 9520381
TI  - HIV-1 Vpr interacts with a human 34-kDa mov34 homologue, a cellular factor linked
      to the G2/M phase transition of the mammalian cell cycle.
AB  - Several important and possibly interrelated functions have been identified for
      the HIV-1 accessory gene product Vpr. These include import of the HIV reverse
      transcription complex into the nucleus of nondividing cells, cellular
      differentiation including cell cycle arrest at the G2/M phase border, immune
      suppression, and enhancement of virus replication. We have cloned a candidate Vpr
      ligand, termed human Vpr interacting protein (hVIP/MOV34), by using a yeast two
      hybrid assay. This gene is homologous to a simultaneously identified 34-kDa human
      mov34 homologue. The MOV34 family includes proteins that function as
      transcriptional and proteolytic regulators of cell growth and differentiation. We
      demonstrate direct interactions between the putative ligand hVIP/MOV34 and Vpr in
      vitro and in vivo. hVIP/MOV34 localizes to the nucleus and appears to function as
      a component of the cell cycle cascade. We observe an association between the
      induction of cell cycle arrest at the G2/M phase border by Vpr and a change in
      the subcellular localization of hVIP/MOV34 from a nuclear to a perinuclear
      localization. This was further associated with the inhibition of maturation
      promoting factor-associated histone H1 kinase activity. We conclude that
      hVIP/MOV34 is involved in the regulation of the cell cycle and a likely cellular
      cofactor for HIV-1 Vpr.

PMID- 9520382
TI  - The transmembrane domain in viral fusion: essential role for a conserved glycine
      residue in vesicular stomatitis virus G protein.
AB  - The transmembrane (TM) domains of viral fusion proteins are required for fusion,
      but their precise role is unknown. G protein, the fusion protein of vesicular
      stomatitis virus, was previously shown to lose syncytia-forming ability if six
      residues (GLIIGL) were deleted from its TM domain. The 20-residue TM domain of
      wild-type (TM20) G protein was thus changed into a TM domain of 14 residues
      (TM14). To assess possible sequence specificity for this loss of function, the
      two Gly residues in TM20 were replaced with either Ala or Leu. Both mutations
      resulted in complete loss of fusion activity, as measured by fusion-dependent
      reporter gene transfer. Single substitutions decreased activity by about half.
      TM14 was weakly active (15%) but reintroduction of a Gly residue into TM14 by a
      single Ile --> Gly substitution increased activity to 80%. All mutants retained
      normal hemifusion activity, i.e., lipid mixing between the outer leaflets of the
      reacting membranes. Thus, at least one TM Gly residue is required for a late step
      in fusion mediated by G protein. Gly residues were significantly (2.6-fold; P =
      0.004) more abundant in the TM domains of viral fusion proteins than in those of
      nonfusion proteins and were distributed differently within the TM domain. Thus,
      Gly residues in the TM domain of other viral fusion proteins may also prove to be
      important for fusion activity.

PMID- 9520383
TI  - How Cro and lambda-repressor distinguish between operators: the structural basis
      underlying a genetic switch.
AB  - Knowledge of the three-dimensional structures of the lambda-Cro and lambda
      repressor proteins in complex with DNA has made it possible to evaluate how these
      proteins discriminate between different operators in phage lambda. As anticipated
      in previous studies, the helix-turn-helix units of the respective proteins bind
      in very different alignments. In Cro the recognition helices are 29 A apart and
      are tilted by 55 degrees with respect to each other, but bind parallel to the
      major groove of the DNA. In lambda-repressor [Beamer, L. J. & Pabo, C. O. (1992)
      J. Mol. Biol. 227, 177-196] the helices are 34 A apart and are essentially
      parallel to each other, but are inclined to the major grooves. The DNA is much
      more bent when bound by Cro than in the case with lambda-repressor. The first two
      amino acids of the recognition helices of the two proteins, Gln-27 and Ser-28 in
      Cro, and Gln-44 and Ser-45 in lambda-repressor, make very similar interactions
      with the invariant bps 2 and 4. There are also analogous contacts between the
      thymine of bp 5 and, respectively, the backbone of Ala-29 of Cro and the backbone
      of Gly-46 of lambda-repressor. Otherwise, however, unrelated parts of the two
      proteins are used in sequence-specific recognition. It appears that similar
      contacts to the invariant or almost invariant bps (especially 2 and 4) are used
      by both Cro and lambda-repressor to differentiate the operator sites as a group
      from other sites on the DNA. The discrimination of Cro and lambda-repressor
      between their different operators is more subtle and seems to be achieved
      primarily through differences in van der Waals contacts at bp 3', together with
      weaker, less direct effects at bps 5' and 8', all in the nonconsensus half of the
      operators. The results provide further support for the idea that there is no
      simple code for DNA-protein recognition.

PMID- 9520384
TI  - The crystal structure of a 3D domain-swapped dimer of RNase A at a 2.1-A
      resolution.
AB  - The dimer of bovine pancreatic ribonuclease A (RNase A) discovered by Crestfield,
      Stein, and Moore in 1962 has been crystallized and its structure determined and
      refined to a 2.1-A resolution. The dimer is 3D domain-swapped. The N-terminal
      helix (residues 1-15) of each subunit is swapped into the major domain (residues
      23-124) of the other subunit. The dimer of bull seminal ribonuclease (BS-RNase)
      is also known to be domain-swapped, but the relationship of the subunits within
      the two dimers is strikingly different. In the RNase A dimer, the 3-stranded beta
      sheets of the two subunits are hydrogen-bonded at their edges to form a
      continuous 6-stranded sheet across the dimer interface; in the BS-RNase dimer, it
      is instead the two helices that abut. Whereas the BS-RNase dimer has 2-fold
      molecular symmetry, the two subunits of the RNase A dimer are related by a
      rotation of approximately 160 degrees. Taken together, these structures show that
      intersubunit adhesion comes mainly from the swapped helical domain binding to the
      other subunit in the "closed interface" but that the overall architecture of the
      domain-swapped oligomer depends on the interactions in the second type of
      interface, the "open interface." The RNase A dimer crystals take up the dye Congo
      Red, but the structure of a Congo Red-stained crystal reveals no bound dye
      molecule. Dimer formation is inhibited by excess amounts of the swapped helical
      domain. The possible implications for amyloid formation are discussed.

PMID- 9520385
TI  - Rack-induced metal binding vs. flexibility: Met121His azurin crystal structures
      at different pH.
AB  - The rack-induced bonding mechanism of metals to proteins is a useful concept for
      explaining the generation of metal sites in electron transfer proteins, such as
      the blue copper proteins, that are designed for rapid electron transfer. The
      trigonal pyramidal structure imposed by the protein with three strong equatorial
      ligands (one Cys and two His) provides a favorable geometry for both cuprous and
      cupric oxidation states. However, the crystal structures of the Met121His mutant
      of azurin from Alcaligenes denitrificans at pH 6.5 (1.89- and 1.91-A resolutions)
      and pH 3.5 (2.45-A resolution) show that the preformed metal binding cavity in
      the protein is more flexible than expected. At high pH (6.5), the Cu site retains
      the same three equatorial ligands as in the wild-type azurin and adds His121 as a
      fourth strong ligand, creating a tetrahedral copper site geometry with a green
      color referred to as 1.5 type. In the low pH (3.5) structure, the protonation of
      His121 causes a conformational change in residues 117-123, moving His121 away
      from the copper. The empty coordination site is occupied by an oxygen atom of a
      nitrate molecule of the buffer solution. This axial ligand is coordinated less
      strongly, generating a distorted tetrahedral copper geometry with a blue color
      and spectroscopic properties of a type-1 site. These crystal structures
      demonstrate that blue copper proteins are flexible enough to permit a range of
      movement of the Cu atom along the axial direction of the trigonal pyramid.

PMID- 9520386
TI  - IPF2alpha-I: an index of lipid peroxidation in humans.
AB  - Isoprostanes are prostaglandin isomers produced from arachidonic acid by a free
      radical-catalyzed mechanism. Urinary excretion of 8-iso-prostaglandin F2alpha, an
      isomer of the PGG/H synthase (cyclooxygenase or COX) enzyme product,
      prostaglandin F2alpha (PGF2alpha), has exhibited promise as an index of oxidant
      stress in vivo. We have developed a quantitative method to measure isoprostane
      F2alpha-I, (IPF2alpha-I) a class I isomer (8-iso-PGF2alpha is class IV), using
      gas chromatography/mass spectrometry. IPF2alpha-I is severalfold as abundant in
      human urine as 8-iso-PGF2alpha, with mean values of 737 +/- 20.6 pg/mg
      creatinine. Both isoprostanes are formed in a free radical-dependent manner in
      low density lipoprotein oxidized by copper in vitro. However, IPF2alpha-I, unlike
      8-iso-PGF2alpha, is not formed in a COX-dependent manner by platelets activated
      by thrombin or collagen in vitro. Similarly, COX inhibition in vivo has no effect
      on IPF2alpha-I. Neither serum IPF2alpha-I, an index of cellular capacity to
      generate the isoprostane, nor urinary excretion of IPF2alpha-I, an index of
      actual generation in vivo, is depressed by aspirin or indomethacin. In contrast,
      both serum thromboxane B2 and urinary excretion of its 11-dehydro metabolite are
      depressed by the COX inhibitors. Although serum 8-iso-PGF2alpha formation is
      substantially depressed by COX inhibitors, urinary excretion of the compound is
      unaffected. Urinary IPF2alpha-I is elevated in cigarette smokers compared with
      controls (1525 +/- 180 versus 740 +/- 40 pg/mg creatinine; P < 0.01) and is
      highly correlated with urinary 8-iso-PGF2alpha (r = 0.9; P < 0.001). Urinary
      IPF2alpha-I is a novel index of lipid peroxidation in vivo, which can be measured
      with precision and sensitivity. It is an abundant F2-isoprostane formed in a free
      radical- but not COX-dependent manner. Although 8-iso-PGF2alpha may be formed as
      a minor product of COX, this pathway contributes trivially, if at all, to levels
      in urine. Urinary excretion of both isoprostanes is elevated in cigarette
      smokers.

PMID- 9520387
TI  - Transcriptional sequencing: A method for DNA sequencing using RNA polymerase.
AB  - We have developed a sequencing method based on the RNA polymerase chain
      termination reaction with rhodamine dye attached to 3'-deoxynucleoside
      triphosphate (3'-dNTP). This method enables us to conduct a rapid isothermal
      sequencing reaction in <30 min, to reduce the amount of template required, and to
      do PCR direct sequencing without the elimination of primers and 2'-dNTP, which
      disturbs the Sanger sequencing reaction. An accurate and longer read length was
      made possible by newly designed four-color dye-3'-dNTPs and mutated RNA
      polymerase with an improved incorporation rate of 3'-dNTP. This method should be
      useful for large-scale sequencing in genome projects and clinical diagnosis.

PMID- 9520388
TI  - Myeloid-specific transcriptional activation by murine myeloid zinc-finger protein
      2.
AB  - Myeloid zinc finger protein 2 (MZF-2) is a zinc-finger transcription factor that
      is expressed in myeloid cells, particularly in the cells committed to the
      neutrophilic lineage. Here we examine the ability of murine MZF-2 (mMZF-2) to
      activate transcription. The mMZF-2 protein binds to a DNA element (MZF-binding
      site) through its zinc-finger domain. When the intact mMZF-2 was cotransfected
      with a reporter gene, it did not activate transcription. However, N-terminal
      deletion mutants greatly enhanced transcription specifically in myeloid cells.
      Furthermore, in an in vivo competition assay, the middle region of MZF-2
      inhibited the mMZF-2-mediated transcription activation. These results suggest
      that mMZF-2 is a transcriptional factor that can specifically work in myeloid
      cells and can be divided into at least three functional domains. The N-terminal
      domain inhibits transactivation by masking the effect of the activation domain.
      The middle region recruits a coactivator, which is responsible for myeloid
      specific transcriptional activation. The C-terminal zinc-finger domain functions
      as a DNA-binding domain.

PMID- 9520389
TI  - Derepression of the C/EBPalpha gene during adipogenesis: identification of AP
      2alpha as a repressor.
AB  - During adipogenesis, CCAAT/enhancer binding protein alpha (C/EBPalpha) serves as
      a pleiotropic transcriptional activator of adipocyte genes. Previously, we
      identified dual repressive elements in the C/EBPalpha gene and a putative
      transacting factor (C/EBPalpha undifferentiated protein, or CUP) expressed by
      preadipocytes, but not adipocytes, that bind to these elements. In the present
      investigation, CUP was purified 17,000-fold from nuclear extracts of 3T3-L1
      preadipocytes. Amino acid sequence and mass spectral analysis of tryptic peptides
      derived from purifed CUP (molecular mass approximately 50 kDa) revealed that the
      repressor is (or contains) an isoform of the transcription factor, AP-2alpha.
      Electrophoretic mobility shift and Western blot analysis on purified CUP and
      preadipocyte nuclear extracts confirmed the identity of CUP as AP-2alpha. Both AP
      2alpha protein and CUP binding activity are expressed by preadipocytes and then
      decrease concomitantly during differentiation of 3T3-L1 preadipocytes into
      adipocytes. Consistent with a repressive role of AP-2alpha/CUP, an AP-2alpha1
      expression vector, cotransfected with a C/EBPalpha promoter-reporter construct
      into 3T3-L1 adipocytes, inhibited reporter gene transcription. Taken together
      with previous results, these findings suggest that in preadipocytes the
      C/EBPalpha gene is repressed by AP-2alpha/CUP, which, upon induction of
      differentiation, is down-regulated, allowing expression of the gene.

PMID- 9520390
TI  - Structure and mechanism of a proline-specific aminopeptidase from Escherichia
      coli.
AB  - The structure of the proline-specific aminopeptidase (EC 3.4.11.9) from
      Escherichia coli has been solved and refined for crystals of the native enzyme at
      a 2.0-A resolution, for a dipeptide-inhibited complex at 2.3-A resolution, and
      for a low-pH inactive form at 2.7-A resolution. The protein crystallizes as a
      tetramer, more correctly a dimer of dimers, at both high and low pH, consistent
      with observations from analytical ultracentrifuge studies that show that the
      protein is a tetramer under physiological conditions. The monomer folds into two
      domains. The active site, in the larger C-terminal domain, contains a dinuclear
      manganese center in which a bridging water molecule or hydroxide ion appears
      poised to act as the nucleophile in the attack on the scissile peptide bond of
      Xaa-Pro. The metal-binding residues are located in a single subunit, but the
      residues surrounding the active site are contributed by three subunits. The fold
      of the protein resembles that of creatine amidinohydrolase (creatinase, not a
      metalloenzyme). The C-terminal catalytic domain is also similar to the single
      domain enzyme methionine aminopeptidase that has a dinuclear cobalt center.

PMID- 9520391
TI  - Thiolate ligands in metallothionein confer redox activity on zinc clusters.
AB  - We postulate a novel and general mechanism in which the redox-active sulfur donor
      group of cyst(e)ine confers oxidoreductive characteristics on stable zinc sites
      in proteins. Thus, the present, an earlier, and accompanying manuscripts [Maret,
      W., Larsen, K. S. & Vallee, B. L. (1997) Proc. Natl. Acad. Sci. USA 94, 2233
      2237; Jiang, L.-J., Maret, W. & Vallee, B. L. (1998) Proc. Natl. Acad. Sci. USA
      95, 3483-3488; and Jacob, C., Maret, W. & Vallee, B. L. (1998) Proc. Natl. Acad.
      Sci. USA 95, 3489-3494] demonstrate that the interactive network featuring
      multiple zinc/sulfur bonds as found in the clusters of metallothionein (MT)
      constitutes a coordination unit critical for the concurrent oxidation of cysteine
      ligands and the ensuing release of zinc. The low position of MT (<-366 mV) on a
      scale of redox reagents allows its effective oxidation by relatively mild
      cellular oxidants, in particular disulfides. When MT is exposed to an excess of
      dithiodipyridine, all of its 20 cysteines are oxidized within 1 hr with the
      concomitant release of all 7 zinc atoms; similarly, the thiol/disulfide
      oxidoreductase DsbA reacts stoichiometrically with MT to release zinc. Zinc and
      sulfur ligands in the clusters are in a spatial arrangement that seemingly favors
      disulfide bond formation. Jointly, this and the above-mentioned manuscripts
      conclude that the control of cellular zinc distribution as a function of the
      energy state of the cell is the long sought role of MT. This specific MT function
      renders dubious the widely held belief that MT primarily scavenges radicals or
      detoxifies metals and is consistent with the frequent use of cysteine as a zinc
      ligand in proteins as a means of both tight and weak zinc binding of thiols and
      disulfides, respectively. Thus, we relate changes in the reducing power of the
      cell to the stability of the zinc/sulfur network in MT and the relative mobility
      of zinc and its control.

PMID- 9520392
TI  - The glutathione redox couple modulates zinc transfer from metallothionein to zinc
      depleted sorbitol dehydrogenase.
AB  - The release and transfer of zinc from metallothionein (MT) to zinc-depleted
      sorbitol dehydrogenase (EC 1.1.1.14) in vitro has been used to explore the role
      of MT in cellular zinc distribution. A 1:1 molar ratio of MT to sorbitol
      dehydrogenase is required for full reactivation, indicating that only one of the
      seven zinc atoms of MT is transferred in this process. Reduced glutathione (GSH)
      and glutathione disulfide (GSSG) are critical modulators of both the rate of zinc
      transfer and the ultimate number of zinc atoms transferred. GSSG increases the
      rate of zinc transfer 3-fold, and its concentration is the major determinant for
      efficient zinc transfer. GSH has a dual function. In the absence of GSSG, it
      inhibits zinc transfer from MT, indicating that MT is in a latent state under the
      relatively high cellular concentrations of GSH. In addition, it primes MT for the
      reaction with GSSG by enhancing the rate of zinc transfer 10-fold and by
      increasing the number of zinc atoms transferred to four. 65Zn-labeling
      experiments confirm the release of one zinc from MT in the absence of glutathione
      and the more effective release of zinc in the presence of GSH and GSSG. In vivo,
      MT may keep the cellular concentrations of free zinc very low and, acting as a
      temporary cellular reservoir, release zinc in a process that is dynamically
      controlled by its interactions with both GSH and GSSG. These results suggest that
      a change of the redox state of the cell could serve as a driving force and signal
      for zinc distribution from MT.

PMID- 9520393
TI  - Control of zinc transfer between thionein, metallothionein, and zinc proteins.
AB  - Metallothionein (MT), despite its high metal binding constant (KZn = 3.2 x 10(13)
      M-1 at pH 7.4), can transfer zinc to the apoforms of zinc enzymes that have
      inherently lower stability constants. To gain insight into this paradox, we have
      studied zinc transfer between zinc enzymes and MT. Zinc can be transferred in
      both directions-i.e., from the enzymes to thionein (the apoform of MT) and from
      MT to the apoenzymes. Agents that mediate or enhance zinc transfer have been
      identified that provide kinetic pathways in either direction. MT does not
      transfer all of its seven zinc atoms to an apoenzyme, but apparently contains at
      least one that is more prone to transfer than the others. Modification of thiol
      ligands in MT zinc clusters increases the total number of zinc ions released and,
      hence, the extent of transfer. Aside from disulfide reagents, we show that
      selenium compounds are potential cellular enhancers of zinc transfer from MT to
      apoenzymes. Zinc transfer from zinc enzymes to thionein, on the other hand, is
      mediated by zinc-chelating agents such as Tris buffer, citrate, or glutathione.
      Redox agents are asymmetrically involved in both directions of zinc transfer. For
      example, reduced glutathione mediates zinc transfer from enzymes to thionein,
      whereas glutathione disulfide oxidizes MT with enhanced release of zinc and
      transfer of zinc to apoenzymes. Therefore, the cellular redox state as well as
      the concentration of other biological chelating agents might well determine the
      direction of zinc transfer and ultimately affect zinc distribution.

PMID- 9520394
TI  - In vitro disassembly and reassembly of an ABC transporter, the histidine
      permease.
AB  - The membrane-bound complex of the Salmonella typhimurium periplasmic histidine
      permease, a member of the ABC transporters (or traffic ATPases) superfamily, is
      composed of two integral membrane proteins, HisQ and HisM, and two copies of an
      ATP-binding subunit, HisP. The complex hydrolyzes ATP upon induction of the
      activity by the liganded soluble receptor, the periplasmic histidine-binding
      protein, HisJ. Here we take advantage of the modular organization of this system
      to show that the nucleotide-binding component can be stripped off the integral
      membrane components, HisQ and HisM. The complex can be reconstituted by using the
      HisP-depleted membranes containing HisQ and HisM and pure soluble HisP. We show
      that HisP has high affinity for the HisP-depleted complex, HisQM, and that two
      HisP molecules are recruited independently of each other for each HisQM unit. The
      in vitro reassembled complex has entirely normal properties, responding to HisJ
      and ATPase inhibitors with the same characteristics as the original complex and
      in contrast to those of soluble HisP. These results show that HisP is absolutely
      required for ATP hydrolysis, that HisQM cannot hydrolyze ATP, that HisP depends
      on HisQM to relay the inducing signal from the soluble receptor, HisJ, and that
      HisQM regulates the ATPase activity of HisP. We also show that HisP changes
      conformation upon exposure to phospholipids.

PMID- 9520395
TI  - Gene rearrangement attenuates expression and lethality of a nonsegmented negative
      strand RNA virus.
AB  - The nonsegmented negative strand RNA viruses comprise hundreds of human, animal,
      insect, and plant pathogens. Gene expression of these viruses is controlled by
      the highly conserved order of genes relative to the single transcriptional
      promoter. We utilized this regulatory mechanism to alter gene expression levels
      of vesicular stomatitis virus by rearranging the gene order. This report
      documents that gene expression levels and the viral phenotype can be manipulated
      in a predictable manner. Translocation of the promoter-proximal nucleocapsid
      protein gene N, whose product is required stoichiometrically for genome
      replication, to successive positions down the genome reduced N mRNA and protein
      expression in a stepwise manner. The reduction in N gene expression resulted in a
      stepwise decrease in genomic RNA replication. Translocation of the N gene also
      attenuated the viruses to increasing extents for replication in cultured cells
      and for lethality in mice, without compromising their ability to elicit
      protective immunity. Because monopartite negative strand RNA viruses have not
      been reported to undergo homologous recombination, gene rearrangement should be
      irreversible and may provide a rational strategy for developing stably attenuated
      live vaccines against this type of virus.

PMID- 9520396
TI  - Identification of a transient excision intermediate at the crossroads between DNA
      polymerase extension and proofreading pathways.
AB  - DNA polymerases achieve accurate DNA replication through a delicate balance
      between primer elongation and proofreading. While insufficient proofreading
      results in DNA replication errors, indiscriminate removal of correct along with
      incorrect nucleotides is wasteful and may prevent completion of DNA synthesis.
      The transition between polymerization and proofreading modes is proposed to be
      governed by a kinetic barrier that prevents proofreading unless the rate of
      primer elongation is significantly reduced by the presence of an incorrect base
      pair at the primer-terminus. We have used mutational analysis, coupled with a
      sensitive, fluorescence-based assay to characterize intermediate steps in the
      proofreading pathway. A highly fluorescent complex forms between the
      bacteriophage T4 DNA polymerase and DNA primer-templates labeled at the 3'
      terminus with the base analog 2-aminopurine. Formation of the fluorescent complex
      appears to be a rate-determining step in the proofreading pathway and is impaired
      for several mutator T4 DNA polymerases with amino acid substitutions in the
      exonuclease domain. Although these mutant DNA polymerases are proficient in
      hydrolysis, their reduced ability to form the fluorescent complex imposes a
      higher kinetic barrier. As a consequence, the mutant DNA polymerases proofread
      less frequently, resulting in more DNA replication errors.

PMID- 9520398
TI  - A role for histone deacetylase activity in HDAC1-mediated transcriptional
      repression.
AB  - Treatment of mammalian cells with small molecule histone deacetylase (HDAC)
      inhibitors induces changes in the transcription of specific genes. These changes
      correlate directly with an increase in the acetylation levels of all four core
      histones in vivo. Antibodies directed against endogenous HDAC1, HDAC2, or HDAC3
      immunoprecipitate histone deacetylase activity that is inhibited in vitro by the
      small molecule trapoxin (TPX), and all three HDACs are retained by a TPX-affinity
      matrix. HDAC1 and HDAC2 are associated in HeLa cells in a complex that is
      predominantly separate from an HDAC3 immune complex. Both Jurkat HDAC1 and HeLa
      HDAC1/2 immune complexes deacetylate all four core histones and recombinant HDAC1
      deacetylates free and nucleosomal histones in vitro. Purified recombinant HDAC1
      deacetylates core histones in the absence of protein cofactors. Site-directed
      mutagenesis was used to identify residues required for the enzymatic and
      structural integrity of HDAC1. Mutation of any one of four conserved residues
      causes deleterious effects on deacetylase activity and a reduced ability to bind
      a TPX-affinity matrix. A subset of these mutations also cause a decreased
      interaction with the HDAC1-associated proteins RbAp48 and mSin3A. Disruption of
      histone deacetylase activity either by TPX or by direct mutation of a histidine
      presumed to be in the active site abrogates HDAC1-mediated transcriptional
      repression of a targeted reporter gene in vivo.

PMID- 9520399
TI  - 23S rRNA positions essential for tRNA binding in ribosomal functional sites.
AB  - rRNA plays an important role in function of peptidyl transferase, the catalytic
      center of the ribosome responsible for the peptide bond formation. Proper
      placement of the peptidyl transferase substrates, peptidyl-tRNA and aminoacyl
      tRNA, is essential for catalysis of the transpeptidation reaction and protein
      synthesis. In this report, we define a small set of rRNA nucleotides that are
      most likely directly involved in binding of tRNA in the functional sites of the
      large ribosomal subunit. By binding biotinylated tRNA substrates to randomly
      modified large ribosomal subunits from Escherichia coli and capturing resulting
      complexes on the avidin resin, we identified four nucleotides in the large
      ribosomal subunit rRNA (positions G2252, A2451, U2506, and U2585) whose
      modifications prevent binding of a peptidyl-tRNA analog in the P site and one
      residue (U2555) whose modification interferes with transfer of peptidyl moiety to
      puromycin. These nucleotides represent a subset of positions protected by tRNA
      analogs from chemical modification and significantly narrow the number of 23S
      rRNA nucleotides that may be directly involved in tRNA binding in the ribosomal
      functional sites.

PMID- 9520397
TI  - Membrane physical state controls the signaling mechanism of the heat shock
      response in Synechocystis PCC 6803: identification of hsp17 as a "fluidity gene".
AB  - The fluidity of Synechocystis membranes was adjusted in vivo by temperature
      acclimation, addition of fluidizer agent benzyl alcohol, or catalytic lipid
      hydrogenation specific to plasma membranes. The reduced membrane physical order
      in thylakoids obtained by either downshifting growth temperature or
      administration of benzyl alcohol was paralleled with enhanced thermosensitivity
      of the photosynthetic membrane. Simultaneously, the stress-sensing system leading
      to the cellular heat shock (HS) response also has been altered. There was a close
      correlation between thylakoid fluidity levels, monitored by steady-state 1,6
      diphenyl-1,3,5-hexatriene anisotropy, and threshold temperatures required for
      maximal activation of all of the HS-inducible genes investigated, including dnaK,
      groESL, cpn60, and hsp17. The causal relationship between the pre-existing
      thylakoid physical order and temperature set point of both the transcriptional
      activation and the de novo protein synthesis was the most striking for the 17-kDa
      HS protein (HSP17) associated mostly with the thylakoid membranes. These findings
      together with the fact that the in vivo modulation of lipid saturation within
      cytoplasmic membrane had no effect on HS response suggest that thylakoid acts as
      a cellular thermometer where thermal stress is sensed and transduced into a
      cellular signal leading to the activation of HS genes.

PMID- 9520400
TI  - The domain organization of NaeI endonuclease: separation of binding and
      catalysis.
AB  - NaeI is a remarkable type II restriction endonuclease. It must bind two
      recognition sequences to cleave DNA, forms a covalent protein-DNA intermediate,
      and is only 1 aa change away from topoisomerase and recombinase activity. The
      latter activities apparently derive from reactivation of a cryptic DNA ligase
      active site. Here, we demonstrate that NaeI has two protease-resistant domains,
      involving approximately the N-terminal and C-terminal halves of the protein,
      linked by a protease-accessible region of 30 aa. The domains were purified by
      cloning. The C-terminal domain was shown by gel mobility-shift assay to have
      approximately 8-fold lower DNA-binding ability than intact NaeI. Analytical
      ultracentrifugation showed this domain to be a monomer in solution. The N
      terminal domain, which contains the catalytic region defined by random
      mutagenesis, did not bind DNA and was a mixture of different-sized complexes in
      solution implying that it mediates self-association. DNA greatly inhibited
      proteolysis of the linker region. The results identify the DNA-binding domain,
      imply that DNA cleavage and recognition are independent and separable, and lead
      us to speculate about a cleft-like structure for NaeI.

PMID- 9520401
TI  - Differential regulation of IkappaB kinase alpha and beta by two upstream kinases,
      NF-kappaB-inducing kinase and mitogen-activated protein kinase/ERK kinase kinase
      1.
AB  - NF-kappaB is activated by various stimuli including inflammatory cytokines and
      stresses. A key step in the activation of NF-kappaB is the phosphorylation of its
      inhibitors, IkappaBs, by an IkappaB kinase (IKK) complex. Recently, two closely
      related kinases, designated IKKalpha and IKKbeta, have been identified to be the
      components of the IKK complex that phosphorylate critical serine residues of
      IkappaBs for degradation. A previously identified NF-kappaB-inducing kinase
      (NIK), which mediates NF-kappaB activation by TNFalpha and IL-1, has been
      demonstrated to activate IKKalpha. Previous studies showed that mitogen-activated
      protein kinase/ERK kinase kinase-1 (MEKK1), which constitutes the c-Jun N
      terminal kinase/stress-activated protein kinase pathway, also activates NF-kappaB
      by an undefined mechanism. Here, we show that overexpression of MEKK1
      preferentially stimulates the kinase activity of IKKbeta, which resulted in
      phosphorylation of IkappaBs. Moreover, a catalytically inactive mutant of IKKbeta
      blocked the MEKK1-induced NF-kappaB activation. By contrast, overexpression of
      NIK stimulates kinase activities of both IKKalpha and IKKbeta comparably,
      suggesting a qualitative difference between NIK- and MEKK1-mediated NF-kappaB
      activation pathways. Collectively, these results indicate that NIK and MEKK1
      independently activate the IKK complex and that the kinase activities of IKKalpha
      and IKKbeta are differentially regulated by two upstream kinases, NIK and MEKK1,
      which are responsive to distinct stimuli.

PMID- 9520402
TI  - Protein splicing in trans by purified N- and C-terminal fragments of the
      Mycobacterium tuberculosis RecA intein.
AB  - Protein splicing involves the self-catalyzed excision of protein splicing
      elements, or inteins, from flanking polypeptide sequences, or exteins, leading to
      the formation of new proteins in which the exteins are linked directly by a
      peptide bond. To study the enzymology of this interesting process we have
      expressed and purified N- and C-terminal segments of the Mycobacterium
      tuberculosis RecA intein, each approximately 100 amino acids long, fused to
      appropriate exteins. These fragments were reconstituted into a functional protein
      splicing element by renaturation from 6 M urea. When renaturation was carried out
      in the absence of thiols, the reconstituted splicing element accumulated as an
      inactive disulfide-linked complex of the two intein fragments, which could be
      induced to undergo protein splicing by reduction of the disulfide bond. This
      provided a useful tool for separately investigating the requirements for the
      reconstitution of the intein fragments to yield a functional protein splicing
      element and for the protein splicing process per se. For example, the pH
      dependence of these processes was quite different, with reconstitution being most
      efficient at pH 8.5 and splicing most rapid at pH 7.0. The availability of such
      an in vitro protein splicing system opens the way for the exploration of intein
      structure and the unusual enzymology of protein splicing. In addition, this trans
      splicing system is a potential protein ligase that can link any two polypeptides
      fused to the N- and C-terminal intein segments.

PMID- 9520403
TI  - Stimulation of p70S6 kinase via a growth hormone-controlled phosphatidylinositol
      3-kinase pathway leads to the activation of a PDE4A cyclic AMP-specific
      phosphodiesterase in 3T3-F442A preadipocytes.
AB  - The challenge of 3T3-F442A fibroblasts with growth hormone led to both a decrease
      in the mobility on SDS/PAGE and activation of the PDE4A cyclic AMP-specific
      phosphodiesterase isoform PDE4A5. Activation was mediated by a JAK-2-dependent
      pathway coupled to the activation of phosphatidylinositol 3-kinase and p70S6
      kinase. Activation was not dependent on the ability of growth hormone to
      stimulate ERK2 or protein kinase C or any effect on transcription. Blockade of
      activation of murine PDE4A5 ablated the ability of growth hormone to decrease
      intracellular cAMP levels. Antisense depletion of murine PDE4A5 mimicked the
      ability of rolipram to enhance the growth hormone-stimulated differentiation of
      3T3-F442A cells to adipocytes. It is suggested that activation of PDE4A5 by
      growth hormone serves as a brake on the differentiation processes.

PMID- 9520404
TI  - Epoxidation of olefins by cytochrome P450: evidence from site-specific
      mutagenesis for hydroperoxo-iron as an electrophilic oxidant.
AB  - P450 cytochromes (P450) catalyze many types of oxidative reactions, including the
      conversion of olefinic substrates to epoxides by oxygen insertion. In some
      instances epoxidation leads to the formation of products of physiological
      importance from naturally occurring substrates, such as arachidonic acid, and to
      the toxicity, carcinogenicity, or teratogenicity of foreign compounds, including
      drugs. In the present mechanistic study, the rates of oxidation of model olefins
      were determined with N-terminal-truncated P450s 2B4 and 2E1 and their respective
      mutants in which the threonine believed to facilitate proton delivery to the
      active site was replaced by alanine. Styrene epoxidation, cyclohexene epoxidation
      and hydroxylation to give 1-cyclohexene-3-ol, and cis- or trans-butene
      epoxidation (without isomerization) and hydroxylation to give 2-butene-1-ol were
      all significantly decreased by the 2B4 T302A mutation. Reduced proton delivery in
      this mutant is believed to interfere with the activation of dioxygen to the
      oxenoid species, as shown earlier by decreased hydroxylation of several
      substrates and enhanced aldehyde deformylation via a presumed peroxo
      intermediate. Of particular interest, however, the T303A mutation of P450 2E1
      resulted in enhanced epoxidation of all of the model olefins along with decreased
      allylic hydroxylation of cyclohexene and butene. These results and a comparison
      of the ratios of the rates of epoxidation and hydroxylation support the concept
      that two different species with electrophilic properties, hydroperoxo-iron
      (FeO2H)3+ and oxenoid-iron (FeO)3+, can effect olefin epoxidation. The ability of
      cytochrome P450 to use several different active oxidants generated from molecular
      oxygen may help account for the broad reaction specificity and variety of
      products formed by this versatile catalyst.

PMID- 9520405
TI  - ESA1 is a histone acetyltransferase that is essential for growth in yeast.
AB  - Posttranslational acetylation of core histone amino termini has long been
      associated with transcriptionally active chromatin. Recent reports have
      demonstrated histone acetyltransferase activity in a small group of conserved
      transcriptional regulators directly linked to gene activation. In addition, the
      presence of a putative acetyltransferase domain has been discovered in a group of
      proteins known as the MYST family (for its founding members MOZ, YBF2/SAS3, SAS2,
      and Tip60). Members of this family are implicated in acute myeloid leukemia
      (MOZ), transcriptional silencing in yeast (SAS2 and YBF2/SAS3), HIV Tat
      interaction in humans (Tip60), and dosage compensation in Drosophila (MOF). In
      this report, we express a yeast ORF with homology to MYST family members and show
      it possesses histone acetyltransferase activity. Unlike the other MYST family
      members in Saccharomyces cerevisiae this gene is essential for growth.

PMID- 9520407
TI  - Global flexibility of tertiary structure in RNA: yeast tRNAPhe as a model system.
AB  - The study of RNA structure using x-ray crystallography or NMR has yielded a
      wealth of detailed structural information; however, such approaches do not
      generally yield quantitative information regarding long-range flexibility in
      solution. To address this issue, we describe a solution-based method that is
      capable of characterizing the global flexibilities of nonhelix elements in RNA,
      provided that such elements are flanked by helix (e.g., bulges, internal loops,
      or branches). The "phased tau ratio" method is based on the principle that, for
      RNA molecules possessing two variably phased bends, the relative birefringence
      decay times depend on the flexibility of each bend, not simply the mean bend
      angles. The method is used to examine the overall flexibility of the yeast
      tRNAPhe core (as unmodified transcript). In the presence of magnesium ions, the
      tRNA core is not significantly more flexible than an equivalent length of RNA
      helix. In the absence of divalent ions, the tRNA core gains flexibility under
      conditions where its secondary structure is likely to be largely preserved. The
      phased tau ratio approach should be broadly applicable to nonhelix elements in
      both RNA and DNA and to protein-nucleic acid interactions.

PMID- 9520406
TI  - Diffusion of peroxynitrite across erythrocyte membranes.
AB  - Peroxynitrite anion (ONOO-) is a reactive species of increasingly recognized
      biological relevance that contributes to oxidative tissue damage. At present,
      however, there is limited knowledge about the mechanisms of peroxynitrite
      diffusion through biological compartments. In this work we have studied the
      diffusion of peroxynitrite across erythrocyte membranes. In solution,
      peroxynitrite rapidly reacts with oxyhemoglobin to yield methemoglobin, with k2 =
      (10.4 +/- 0.3) x 10(3) M-1.s-1 at pH 7.4 and 25 degrees C. Addition of
      peroxynitrite to intact erythrocytes caused oxidation of intracellular
      oxyhemoglobin to methemoglobin. Oxidation yields in red blood cells at pH 7.0
      were approximately 40% of those obtained in solution, which results mostly from
      competition of other cytosolic components for peroxynitrite. Indeed, rather small
      differences were observed between oxidation yields in lysates compared with
      intact erythrocytes, in particular at acidic and neutral pH values, indicating
      that membrane was not precluding peroxynitrite diffusion. Incubation of
      erythrocytes at pH 7.0 with 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid
      (DIDS), a specific inhibitor of anion exchange, resulted in up to 50% inhibition
      of oxyhemoglobin oxidation by peroxynitrite. More protection by DIDS was achieved
      at alkaline pH, while no effect was observed at pH 5.5, where 95% of
      peroxynitrite is in the acidic form, ONOOH (pKa = 6.8). In addition,
      peroxynitrite caused nitration of intracellular hemoglobin, in a process that was
      enhanced in thiol-depleted erythrocytes. Our results indicate that peroxynitrite
      is able to cross the erythrocyte membrane by two different mechanisms: in the
      anionic form through the DIDS-inhibitable anion channel, and in the protonated
      form by passive diffusion.

PMID- 9520408
TI  - Oxidized, deaminated cytosines are a source of C --> T transitions in vivo.
AB  - The most common base substitution arising from oxidative damage of DNA is a GC -
      > AT transition. In an effort to determine the oxidized lesion(s) that gives rise
      to this mutation, the mutagenicity of three oxidized cytosines, 5
      hydroxycytosine, 5-hydroxyuracil, and uracil glycol, were investigated in
      Escherichia coli. An M13 viral genome was constructed to contain a single
      oxidized cytosine at a specific site. Replication in vivo of the single-stranded
      genomes yielded mutation frequencies of 0.05%, 83%, and 80% for 5
      hydroxycytosine, 5-hydroxyuracil, and uracil glycol, respectively. The
      predominant mutation observed was C --> T. A model for C --> T oxidative
      mutagenesis is suggested in which initial cytosine oxidation is followed by
      deamination to a poorly repaired uracil derivative that is strongly miscoding
      during replication.

PMID- 9520409
TI  - Structure-based prediction of the stability of transmembrane helix-helix
      interactions: the sequence dependence of glycophorin A dimerization.
AB  - The ability to predict the effects of point mutations on the interaction of alpha
      helices within membranes would represent a significant step toward understanding
      the folding and stability of membrane proteins. We use structure-based empirical
      parameters representing steric clashes, favorable van der Waals interactions, and
      restrictions of side-chain rotamer freedom to explain the relative dimerization
      propensities of 105 hydrophobic single-point mutants of the glycophorin A (GpA)
      transmembrane domain. Although the structure at the dimer interface is critical
      to our model, changes in side-chain hydrophobicity are uncorrelated with dimer
      stability, indicating that the hydrophobic effect does not influence
      transmembrane helix-helix association. Our model provides insights into the
      compensatory effects of multiple mutations and shows that helix-helix
      interactions dominate the formation of specific structures.

PMID- 9520410
TI  - Rational design of a triple helix-specific intercalating ligand.
AB  - DNA triple helices offer new perspectives toward oligonucleotide-directed gene
      regulation. However, the poor stability of some of these structures might limit
      their use under physiological conditions. Specific ligands can intercalate into
      DNA triple helices and stabilize them. Molecular modeling and thermal
      denaturation experiments suggest that benzo[f]pyrido[3, 4-b]quinoxaline
      derivatives intercalate into triple helices by stacking preferentially with the
      Hoogsteen-paired bases. Based on this model, it was predicted that a
      benzo[f]quino[3,4-b]quinoxaline derivative, which possesses an additional
      aromatic ring, could engage additional stacking interactions with the pyrimidine
      strand of the Watson-Crick double helix upon binding of this pentacyclic ligand
      to a triplex structure. This compound was synthesized. Thermal denaturation
      experiments and inhibition of restriction enzyme cleavage show that this new
      compound can indeed stabilize triple helices with great efficiency and
      specificity and/or induce triple helix formation under physiological conditions.

PMID- 9520411
TI  - Osteoclast differentiation factor is a ligand for
      osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to
      TRANCE/RANKL.
AB  - Osteoclasts, the multinucleated cells that resorb bone, develop from
      hematopoietic cells of monocyte/macrophage lineage. Osteoclast-like cells (OCLs)
      are formed by coculturing spleen cells with osteoblasts or bone marrow stromal
      cells in the presence of bone-resorbing factors. The cell-to-cell interaction
      between osteoblasts/stromal cells and osteoclast progenitors is essential for OCL
      formation. Recently, we purified and molecularly cloned osteoclastogenesis
      inhibitory factor (OCIF), which was identical to osteoprotegerin (OPG). OPG/OCIF
      is a secreted member of the tumor necrosis factor receptor family and inhibits
      osteoclastogenesis by interrupting the cell-to-cell interaction. Here we report
      the expression cloning of a ligand for OPG/OCIF from a complementary DNA library
      of mouse stromal cells. The protein was found to be a member of the membrane
      associated tumor necrosis factor ligand family and induced OCL formation from
      osteoclast progenitors. A genetically engineered soluble form containing the
      extracellular domain of the protein induced OCL formation from spleen cells in
      the absence of osteoblasts/stromal cells. OPG/OCIF abolished the OCL formation
      induced by the protein. Expression of its gene in osteoblasts/stromal cells was
      up-regulated by bone-resorbing factors. We conclude that the membrane-bound
      protein is osteoclast differentiation factor (ODF), a long-sought ligand
      mediating an essential signal to osteoclast progenitors for their differentiation
      into osteoclasts. ODF was found to be identical to TRANCE/RANKL, which enhances T
      cell growth and dendritic-cell function. ODF seems to be an important regulator
      in not only osteoclastogenesis but also immune system.

PMID- 9520412
TI  - Cdc6 is regulated by E2F and is essential for DNA replication in mammalian cells.
AB  - Cdc6 has a critical regulatory role in the initiation of DNA replication in
      yeasts, but its function in mammalian cells has not been characterized. We show
      here that Cdc6 is expressed selectively in proliferating but not quiescent
      mammalian cells, both in culture and within tissues of intact animals. During the
      transition from a growth-arrested to a proliferative state, transcription of
      mammalian Cdc6 is regulated by E2F proteins, as revealed by a functional analysis
      of the human Cdc6 promoter and by the ability of exogenously expressed E2F
      proteins to stimulate the endogenous Cdc6 gene. Immunodepletion of Cdc6 by
      microinjection of anti-Cdc6 antibody blocks initiation of DNA replication in a
      human tumor cell line. We conclude that expression of human Cdc6 is regulated in
      response to mitogenic signals though transcriptional control mechanisms involving
      E2F proteins, and that Cdc6 is required for initiation of DNA replication in
      mammalian cells.

PMID- 9520413
TI  - Impact of oncogenes in tumor angiogenesis: mutant K-ras up-regulation of vascular
      endothelial growth factor/vascular permeability factor is necessary, but not
      sufficient for tumorigenicity of human colorectal carcinoma cells.
AB  - Targeted disruption of the single mutant K-ras allele in two human colorectal
      carcinoma cell lines (DLD-1 and HCT-116) leads to loss of tumorigenic competence
      in nude mice with retention of ability to grow indefinitely in monolayer culture.
      Because expression of the mutant K-ras oncogene in these cell lines is associated
      with marked up-regulation of vascular endothelial growth factor/vascular
      permeability factor (VEGF/VPF), we sought to determine whether this potent
      angiogenesis inducer plays a role in K-ras-dependent tumorigenic competence.
      Transfection of a VEGF121 antisense expression vector into DLD-1 and HCT-116
      cells resulted in suppression of VEGF/VPF production by a factor of 3- to 4-fold.
      The VEGF/VPF-deficient sublines, unlike the parental population or vector
      controls, were profoundly suppressed in their ability to form tumors in nude mice
      for as long as 6 months after cell injection. In contrast, in vitro growth of
      these sublines was unaffected, thus demonstrating the critical importance of
      VEGF/VPF as an angiogenic factor for HCT-116 and DLD-1 cells. Transfection of a
      full-length VEGF121 cDNA into two nontumorigenic mutant K-ras knockout sublines
      resulted in a weak but detectable restoration of tumorigenic ability in vivo in a
      subset of the transfectants, with no consistent change in growth properties in
      vitro. The findings indicate that mutant ras-oncogene-dependent VEGF/VPF
      expression is necessary, but not sufficient, for progressive tumor growth in vivo
      and highlight the relative contribution of oncogenes, such as mutant K-ras, to
      the process of tumor angiogenesis.

PMID- 9520414
TI  - Identification of cytokeratin 1 as a binding protein and presentation receptor
      for kininogens on endothelial cells.
AB  - A kininogen binding protein(s), a putative receptor, was identified on
      endothelial cells. A 54-kDa protein was isolated by a biotin-high molecular mass
      kininogen (HK) affinity column that, on aminoterminal sequencing of tryptic
      digests, was identified as cytokeratin 1. Multiple antibodies directed to
      cytokeratin 1 reacted with a 54-kDa band on immunoblot of lysates of endothelial
      cells. On laser scanning confocal microscopy, cytokeratin 1 antigen was found on
      the surface of endothelial cells. Cytokeratin 1 antigen also was detected on
      endothelial cell membranes by flow cytometry. Moreover, an antipeptide antibody
      to a sequence unique to cytokeratin 1 also specifically bound to nonpermeabilized
      endothelial cells. Biotin-HK specifically bound to cytokeratin only in the
      presence of Zn2+, and cytokeratin blocked biotin-HK binding to endothelial cells.
      Further, HK and low molecular mass kininogen, but not factor XII, blocked biotin
      HK binding to cytokeratin, and peptides of each cell binding region of HK on
      domains 3,4, and 5 blocked biotin-HK binding to cytokeratin. gC1qR and soluble
      urokinase-like plasminogen activator receptor also inhibited biotin-HK binding to
      cytokeratin. These investigations identify a new function for cytokeratin 1 as a
      kininogen binding protein. Cytokeratins, members of the family of intermediate
      filament proteins, may represent a new class of receptors.

PMID- 9520415
TI  - The expression of matrix metalloproteinase 9 is enhanced by Epstein-Barr virus
      latent membrane protein 1.
AB  - Matrix metalloproteinases (MMPs) are frequently expressed in malignant tumor
      cells and are thought to play crucial roles in tumor invasion and metastasis.
      Here we report that expression of MMP9 is increased in Epstein-Barr virus (EBV)
      infected type III latency lymphoma cell lines, but not in type I lines where
      latent viral gene expression is highly restricted. Type III cell lines express
      abundant EBV latent membrane protein 1 (LMP1), the principal EBV oncoprotein, as
      well as the other latency proteins including the transcriptional factor, EBV
      nuclear antigen 2, which is also required for cell immortalization. Transfection
      of an LMP1 expression plasmid in the C33A cell line increased MMP9 expression,
      whereas overexpression of EBV nuclear antigen 2 did not. Three motifs, homologous
      to the binding sites of NF-kappaB, SP-1, and AP-1 proteins, contribute to
      induction of the MMP9 promoter by 12-O-tetradecanoyl-phorbol-13-acetate and tumor
      necrosis factor alpha. Here we report that binding sites for NF-kappaB, SP-1, and
      AP-1 also contribute to induction of the MMP9 promoter by the viral protein,
      LMP1, mainly through the NF-kappaB and, to a lesser extent, the SP-1 and AP-1
      sites. Moreover the AP-1 binding site is essential in that mutation of it
      abolished reporter gene induction by LMP1. The enhancement of MMP9 expression was
      blocked by cotransfection of an IkappaB expression plasmid. Thus in addition to
      its transforming properties, the oncoprotein LMP1 may contribute to invasiveness
      and metastasis of EBV-associated tumors such as nasopharyngeal carcinoma.

PMID- 9520416
TI  - Regulation of the Escherichia coli water channel gene aqpZ.
AB  - Osmotic movement of water across bacterial cell membranes is postulated to be a
      homeostatic mechanism for maintaining cell turgor. The molecular water
      transporter remained elusive until discovery of the Escherichia coli water
      channel, AqpZ, however the regulation of the aqpZ gene expression and
      physiological function of the AqpZ protein are unknown. Northern analysis
      revealed a transcript of 0.7 kb, confirming the monocistronic nature of aqpZ.
      Regulatory studies performed with an aqpZ::lacZ low copy plasmid demonstrate
      enhanced expression during mid-logarithmic growth, and expression of the gene is
      dependent upon the extracellular osmolality, which increased in hypoosmotic
      environments but strongly reduced in hyperosmolar NaCl or KCl. While disruption
      of the chromosomal aqpZ is not lethal for E. coli, the colonies of the aqpZ
      knockout mutant are smaller than those of the parental wild-type strain. When
      cocultured with parental wild-type E. coli, the aqpZ knockout mutant exhibits
      markedly reduced colony formation when grown at 39 degrees C. Similarly, the aqpZ
      knockout mutant also exhibits greatly reduced colony formation when grown at low
      osmolality, but this phenotype is reversed by overexpression of AqpZ protein.
      These results implicate AqpZ as a participant in the adaptive response of E. coli
      to hypoosmotic environments and indicate a requirement for AqpZ by rapidly
      growing cells.

PMID- 9520417
TI  - Functional association between Arf and RalA in active phospholipase D complex.
AB  - Activation of phospholipase D1 (PLD1) by Arf has been implicated in vesicle
      transport and membrane trafficking. PLD1 has also been shown to be associated
      with the small GTPase RalA, which functions downstream from Ras in a Ras-RalA
      GTPase cascade that facilitates intracellular signal transduction. Although PLD1
      associates directly with RalA, RalA has no effect upon the activity of PLD1.
      However, PLD1 precipitated from cell lysates with immobilized glutathione S
      transferase-RalA fusion protein is active. This suggests the presence of an
      additional activating factor in the active RalA-PLD1 complexes. Because Arf
      stimulates PLD1, we looked for the presence of Arf in the active RalA-PLD1
      complexes isolated from v-Src- and v-Ras-transformed cell lysates. Low levels of
      Arf protein were detected in RalA-PLD1 complexes; however, if guanosine 5'-[gamma
      thio]triphosphate was added to activate Arf and stimulate translocation to the
      membrane, high levels of Arf were precipitated by RalA from cell lysates.
      Interestingly, deletion of 11 amino-terminal amino acids unique to Ral GTPases,
      which abolished the ability of RalA to precipitate PLD activity, prevented the
      association between RalA and Arf. Brefeldin A, which inhibits Arf GDP-GTP
      exchange, inhibited PLD activity in v-Src- and v-Ras-transformed cells but not in
      the nontransformed cells, suggesting that the association of Arf with RalA is
      required for the increased PLD activity induced by v-Src and v-Ras. These data
      implicate Arf in the transduction of intracellular signals activated by v-Src and
      mediated by the Ras-RalA GTPase cascade. Because both Arf and PLD1 stimulate
      vesicle formation in the Golgi, these data raise the possibility that vesicle
      formation and trafficking may play a role in the transduction of intracellular
      signals.

PMID- 9520418
TI  - Cloned mammalian neutral sphingomyelinase: functions in sphingolipid signaling?
AB  - Sphingomyelin is an abundant constituent of the plasma membranes of mammalian
      cells. Ceramide, its primary catabolic intermediate, is released by either acid
      sphingomyelinase or neutral sphingomyelinase (nSMase) and has emerged as a
      potential lipid signaling molecule. nSMase is regarded as a key enzyme in the
      regulated activation of the "sphingomyelin cycle" and cell signaling. We report
      here the cloning, identification, and functional characterization of murine and
      human nSMase, a ubiquitously expressed integral membrane protein, which displays
      all established properties of the Mg2+-dependent nSMase of the plasma membrane.
      Stably nSMase-overexpressing U937 and human embryonic kidney cell lines have been
      generated for the study of the role of nSMase in signal transduction pathways.
      Their stimulation by tumor necrosis factor alpha leads only to a moderately
      elevated ceramide concentration. Activation of Jun kinase and NFkappaB and
      poly(ADP-ribose) polymerase cleavage are identical in mock- and nSMase
      transfected cells. Tumor necrosis factor alpha triggers the ERK1 pathway in none
      of the cell lines. The cloned nSMase will facilitate further controlled
      experiments aiming at the definition of a possible role of ceramide as signal
      transduction molecule.

PMID- 9520420
TI  - Packaging of intron-containing genes into retrovirus vectors by alphavirus
      vectors.
AB  - Efficient and controllable expression of a transgene usually requires the
      presence of intron sequences and much efforts have been made to produce
      retrovirus vectors that can transduce and integrate genes with introns. However,
      this has proven difficult because the viral RNA is spliced when it is synthesized
      in the nucleus of a producer cell. We describe a novel approach to avoid this
      problem. In our system the retroviral RNA is synthesized in the cytoplasm of the
      cell, not in the nucleus, in a reaction driven by the Semliki Forest virus (SFV)
      expression system. The approach was tested with a recombinant Moloney murine
      leukemia virus genome containing the chloramphenicol acetyltransferase (CAT) gene
      in association with an intron. This was inserted into a SFV transcription plasmid
      and the corresponding SFV vector RNA was transcribed in vitro. BHK-21 cells were
      then transfected with this vector RNA together with two additional SFV vectors
      that encode the Moloney murine leukemia virus packaging proteins. Retrovirus
      vectors containing intron-CAT sequences were produced at titers up to 1.3 x 10(6)
      infectious particles per ml during a 5-hr incubation period. The vectors
      faithfully transduced the intron-containing CAT gene into NIH 3T3 cells, where
      the intron-CAT RNA was subjected to efficient splicing and used for high level
      enzyme expression. Thus, the results show that intron containing genes can be
      efficiently packaged into retrovirus vectors by the SFV expression system.

PMID- 9520419
TI  - Etk/Bmx, a tyrosine kinase with a pleckstrin-homology domain, is an effector of
      phosphatidylinositol 3'-kinase and is involved in interleukin 6-induced
      neuroendocrine differentiation of prostate cancer cells.
AB  - Etk/Bmx is the newest member of Btk tyrosine kinase family that contains a
      pleckstrin homology domain, an src homology 3 domain, an src homology 2 domain,
      and a catalytic domain. Unlike other members of the Btk family kinases, which are
      mostly hemopoietic cell-specific, Etk/Bmx is preferentially expressed in
      epithelial and endothelial cells. We first identified this kinase in prostate
      cancer [Robinson, D., He, F., Pretlow, T. & Kung, H. J. (1996) Proc. Natl. Acad.
      Sci. USA 93, 5958-5962). Here we report that Etk is engaged in
      phosphatidylinositol 3-kinase (PI3-kinase) pathway and plays a pivotal role in
      interleukin 6 (IL-6) signaling in a prostate cancer cell line, LNCaP. Our
      evidence that PI3-kinase is involved in Etk activation includes: (i) Wortmannin,
      a specific inhibitor of PI3-kinase, abolished the activation of Etk by IL-6; (ii)
      a constitutively active p110 subunit of PI3-kinase was able to activate Etk in
      the absence of IL-6; and (iii) a dominant negative p85 subunit of PI3-kinase
      mutant blocked the activation of Etk by IL-6. Interestingly, IL-6 treatment of
      LNCaP induced a remarkable neuroendocrine-like differentiation phenotype, with
      neurite extension and enhanced expression of neuronal markers. This phenotype
      could be abrogated by the overexpression of a dominant-negative Etk, indicating
      Etk is required for this differentiation process.

PMID- 9520421
TI  - Synthetic activation of caspases: artificial death switches.
AB  - The development of safe vectors for gene therapy requires fail-safe mechanisms to
      terminate therapy or remove genetically altered cells. The ideal "suicide switch"
      would be nonimmunogenic and nontoxic when uninduced and able to trigger cell
      death independent of tissue type or cell cycle stage. By using chemically induced
      dimerization, we have developed powerful death switches based on the cysteine
      proteases, caspase-1 ICE (interleukin-1beta converting enzyme) and caspase-3
      YAMA. In both cases, aggregation of the target protein is achieved by a nontoxic
      lipid-permeable dimeric FK506 analog that binds to the attached FK506-binding
      proteins, FKBPs. We find that intracellular cross-linking of caspase-1 or caspase
      3 is sufficient to trigger rapid apoptosis in a Bcl-xL-independent manner,
      suggesting that these conditional proapoptotic molecules can bypass intracellular
      checkpoint genes, such as Bcl-xL, that limit apoptosis. Because these chimeric
      molecules are derived from autologous proteins, they should be nonimmunogenic and
      thus ideal for long-lived gene therapy vectors. These properties should also make
      chemically induced apoptosis useful for developmental studies, for treating
      hyperproliferative disorders, and for developing animal models to a wide variety
      of diseases.

PMID- 9520422
TI  - Structural changes at microtubule ends accompanying GTP hydrolysis: information
      from a slowly hydrolyzable analogue of GTP, guanylyl
      (alpha,beta)methylenediphosphonate.
AB  - Microtubules are dynamic polymers that interconvert between periods of slow
      growth and fast shrinkage. The energy driving this nonequilibrium behavior comes
      from the hydrolysis of GTP, which is required to destabilize the microtubule
      lattice. To understand the mechanism of this destabilization, cryo-electron
      microscopy was used to compare the structure of the ends of shrinking
      microtubules assembled in the presence of either GTP or the slowly hydrolyzable
      analogue guanylyl (alpha,beta)methylenediphosphonate (GMPCPP). Depolymerization
      was induced by cold or addition of calcium. With either nucleotide, we have
      observed curled oligomers at the ends of shrinking microtubules. However, GDP
      oligomers were consistently more curved than GMPCPP oligomers. This difference in
      curvature between depolymerizing GDP and GMPCPP protofilaments suggests that GTP
      hydrolysis is accompanied by an increase in curvature of the protofilaments,
      thereby destabilizing the lateral interactions between tubulin subunits in the
      microtubule lattice.

PMID- 9520423
TI  - The tumor suppressor SMAD4/DPC4 is essential for epiblast proliferation and
      mesoderm induction in mice.
AB  - Members of the transforming growth factor (TGF)-beta superfamily have been shown
      to play a variety of important roles in embryogenesis, including dorsal and
      ventral mesoderm induction. The tumor suppressor SMAD4, also known as DPC4, is
      believed to be an essential factor that mediates TGF-beta signals. To explore
      functions of SMAD4 in development, we have mutated it by truncating its
      functional C-domain. We show that Smad4 is expressed ubiquitously during murine
      embryogenesis. Mice heterozygous for the Smad4(ex8/+) mutation are
      developmentally normal, whereas homozygotes die between embryonic day 6.5 (E6.5)
      and 8.5. All Smad4(ex8/ex8) mutants are developmentally delayed at E6 and show
      little or no elongation in the extraembryonic portion of late egg cylinder stage
      embryos. Consistent with this, cultured Smad4(ex8/ex8) blastocyst outgrowths
      suffer cellular proliferation defects and fail to undergo endoderm
      differentiation. Although a portion of mutant embryos at E8.5 show an increase in
      the embryonic ectoderm and endoderm, morphological and molecular analyses
      indicate that they do not form mesoderm. Altogether, these data demonstrate that
      SMAD4-mediated signals are required for epiblast proliferation, egg cylinder
      formation, and mesoderm induction.

PMID- 9520424
TI  - Over one-half billion years of head conservation? Expression of an ems class gene
      in Hydractinia symbiolongicarpus (Cnidaria: Hydrozoa).
AB  - We report the isolation of an empty spiracles class homeodomain-containing gene,
      Cn-ems, from the hydrozoan Hydractinia symbiolongicarpus, the first gene of this
      class characterized in a lower metazoan. Cn-ems was found to be expressed in the
      head of gastrozooids, specifically in endodermal epithelial cells of the
      taeniolae of the hypostome. Cn-ems is not expressed in gonozooids, which lack
      taeniolae. Experimental conversion of the posterior region of the planula larva
      into head structures up-regulates expression of the gene. These findings
      establish that the association of ems-class genes with head structures preceded
      the evolution of bilateral symmetry.

PMID- 9520425
TI  - Production of medakafish chimeras from a stable embryonic stem cell line.
AB  - Embryonic stem (ES) cell lines provide a unique tool for introducing targeted or
      random genetic alterations through gene replacement, insertional mutagenesis, and
      gene addition because they offer the possibility for in vitro selection for the
      desired, but extremely rare, recombinant genotypes. So far only mouse blastocyst
      embryos are known to have the competence to give rise to such ES cell lines. We
      recently have established a stable cell line (Mes1) from blastulae of the
      medakafish (Oryzias latipes) that shows all characteristics of mouse ES cells in
      vitro. Here, we demonstrate that Mes1 cells also have the competence for chimera
      formation; 90% of host blastulae transplanted with Mes1 cells developed into
      chimeric fry. This high frequency was not compromised by cryostorage or DNA
      transfection of the donor cells. The Mes1 cells contributed to numerous organs
      derived from all three germ layers and differentiated into various types of
      functional cells, most readily observable in pigmented chimeras. These features
      suggest the possibility that Mes1 cells may be a fish equivalent of mouse ES
      cells and that medaka can be used as another system for the application of the ES
      cell technology.

PMID- 9520426
TI  - Competition among body parts in the development and evolution of insect
      morphology.
AB  - Changes in form during ontogeny and evolution depend in large measure on changes
      in the relative growth of the various parts of the body. The current consensus in
      developmental biology is that the final size of appendages and internal organs is
      regulated autonomously, within the structure itself. Size regulation of body
      parts typically requires no external control and is thought to be relatively
      insensitive to signals from the developmental environment. We show in two very
      different systems, butterfly wings and beetle horns, that experimentally induced
      changes in the allocation of developmental resources to one trait produces
      compensatory changes in the relative sizes of other traits. These findings
      illustrate that interaction among body parts in development is part of the
      mechanism of size regulation of those parts. Furthermore, in the case of beetle
      horns, we show that the tradeoff in size is manifest as a significant negative
      genetic correlation among the involved body parts and, therefore, constitutes a
      developmental source of genetic constraint on the evolution of body form.

PMID- 9520427
TI  - A protein with protective properties against the cellular defense reactions in
      insects.
AB  - The molecular mechanism of how insects recognize intruding microorganisms and
      parasites and distinguish them from own body structures is not well known. We
      explored evolutionary adaptations in an insect parasitoid host interaction to
      identify components that interfere with the recognition of foreign objects and
      cellular encapsulation. Because some parasitoids provide protection for the
      developing wasp in the absence of an overt suppression of the insect host
      defense, we analyzed the surface of eggs and symbiotic viruses for protective
      properties. Here we report on the molecular cloning of a 32-kDa protein (Crp32)
      that is one of the major protective components. It is produced in the calyx cells
      of the female wasp ovaries and attached to the surface of the egg and other
      particles including polydnaviruses. The recombinant protein confers protection to
      coated objects in a cellular encapsulation assay suggesting that a layer of Crp32
      may prevent cellular encapsulation reactions by a local inactivation of the host
      defense system.

PMID- 9520428
TI  - Populations can persist in an environment consisting of sink habitats only.
AB  - Populations that live in environments with different habitats have to distribute
      their offspring over these habitats. When population densities go to equilibrium,
      the evolutionary optimum is an ideal free distribution. Under an ideal free
      distribution, no offspring should be put into sink habitats. However, when the
      environmental conditions in a habitat are not constant but fluctuate, allocating
      offspring to sink habitats can increase the long term growth rate of a
      population. We demonstrate this principle in a simple model for offspring
      allocation. As a consequence, it is possible that populations persist in
      environments that only consist of sink habitats.

PMID- 9520429
TI  - Marine latitudinal diversity gradients: tests of causal hypotheses.
AB  - Latitudinal diversity gradients are first-order expressions of diversity patterns
      both on land and in the oceans, although the current hypotheses that seek to
      explain them are based chiefly on terrestrial data. We have assembled a database
      of the geographic ranges of 3,916 species of marine prosobranch gastropods living
      on the shelves of the western Atlantic and eastern Pacific Oceans, from the
      tropics to the Arctic Ocean. Western Atlantic and eastern Pacific diversities are
      similar, and the diversity gradients are strikingly similar despite many
      important physical and historical differences between the oceans. This shared
      diversity pattern cannot be explained by: (i) latitudinal differences in species
      range-length (Rapoport's rule); (ii) species-area effects; or (iii) recent
      geologic histories. One parameter that does correlate significantly with
      diversity in both oceans is solar energy input, as represented by average sea
      surface temperature. If this correlation is causal, sea surface temperature is
      probably linked to diversity through some aspect of productivity. In this case,
      diversity is an evolutionary outcome of trophodynamic processes inherent in
      ecosystems, and not just a byproduct of physical geographies.

PMID- 9520430
TI  - Codon reassignment and amino acid composition in hemichordate mitochondria.
AB  - In the mitochondrial genome of the hemichordate Balanoglossus carnosus, the codon
      AAA, which is assigned to lysine in most metazoans but to asparagine in
      echinoderms, is absent. Furthermore, the lysine tRNA gene carries an anticodon
      substitution that renders its gene product unable to decode AAA codons, whereas
      the asparagine tRNA gene has not changed to encode a tRNA with the ability to
      recognize AAA codons. Thus, the hemichordate mitochondrial genome can be regarded
      as an intermediate in the process of reassignment of mitochondrial AAA codons,
      where most metazoans represent the ancestral situation and the echinoderms the
      derived situation. This lends support to the codon capture hypothesis. We also
      show that the reassignment of the AAA codon is associated with a reduction in the
      relative abundance of lysine residues in mitochondrial proteins.

PMID- 9520431
TI  - Positive Darwinian selection after gene duplication in primate ribonuclease
      genes.
AB  - Evolutionary mechanisms of origins of new gene function have been a subject of
      long-standing debate. Here we report a convincing case in which positive
      Darwinian selection operated at the molecular level during the evolution of novel
      function by gene duplication. The genes for eosinophil cationic protein (ECP) and
      eosinophil-derived neurotoxin (EDN) in primates belong to the ribonuclease gene
      family, and the ECP gene, whose product has an anti-pathogen function not
      displayed by EDN, was generated by duplication of the EDN gene about 31 million
      years ago. Using inferred nucleotide sequences of ancestral organisms, we showed
      that the rate of nonsynonymous nucleotide substitution was significantly higher
      than that of synonymous substitution for the ECP gene. This strongly suggests
      that positive Darwinian selection operated in the early stage of evolution of the
      ECP gene. It was also found that the number of arginine residues increased
      substantially in a short period of evolutionary time after gene duplication, and
      these amino acid changes probably produced the novel anti-pathogen function of
      ECP.

PMID- 9520432
TI  - Major histocompatibility complex variation associated with juvenile survival and
      parasite resistance in a large unmanaged ungulate population.
AB  - Antagonistic coevolution between hosts and parasites has been proposed as a
      mechanism maintaining genetic diversity in both host and parasite populations. In
      particular, the high levels of genetic diversity widely observed at the major
      histocompatibility complex (MHC) of vertebrate hosts are consistent with the
      hypothesis of parasite-driven balancing selection acting to maintain MHC genetic
      diversity. To date, however, empirical evidence in support of this hypothesis,
      especially from natural populations, has been lacking. A large unmanaged
      population of Soay sheep (Ovis aries L.) is used to investigate associations
      between MHC variation, juvenile survival, and parasite resistance. We show in an
      unmanaged, nonhuman population that allelic variation within the MHC is
      significantly associated with differences in both juvenile survival and
      resistance to intestinal nematodes. Certain MHC alleles are associated with low
      survivorship probabilities and high levels of parasitism or vice versa. We
      conclude that parasites are likely to play a major role in the maintenance of MHC
      diversity in this population.

PMID- 9520433
TI  - Strand compositional asymmetry in bacterial and large viral genomes.
AB  - Several bacterial genomes exhibit preference for G over C on the DNA leading
      strand extending from the origin of replication to the ter-region in the genomes
      of Escherichia coli, Mycoplasma genitalium, Bacillus subtilis, and marginally in
      Haemophilus influenzae, Mycoplasma pneumoniae, and Helicobacter pylori. Strand
      compositional asymmetry is not observed in the cyanobacterium Synechocystis sp.
      genome nor in the archaeal genomes of Methanococcus jannaschii, Methanobacterium
      thermoautotrophicum, and Archaeoglobus fulgidus. A strong strand compositional
      asymmetry is observed in beta-type but not alpha- or gamma-type human
      herpesviruses featuring G > C downstream of oriL and C > G upstream of oriL.
      Dinucleotide relative abundances (i.e., dinucleotide representations normalized
      by the component nucleotide frequencies) are consonant with respect to the
      leading and lagging strands. Strand compositional asymmetry may reflect on
      differences in replication synthesis of the leading versus lagging strand, on
      differences between template and coding strand associated with transcription
      coupled repair mechanisms, on differences in gene density between the two
      strands, on differences in residue and codon biases in relation to gene function,
      expression level, or operon organization, or on differences in single or context
      dependent base mutational rates. The absence of strand asymmetry in the archaeal
      genomes may reflect the presence of multiple origins of replication.

PMID- 9520434
TI  - Archaeal translation initiation revisited: the initiation factor 2 and eukaryotic
      initiation factor 2B alpha-beta-delta subunit families.
AB  - As the amount of available sequence data increases, it becomes apparent that our
      understanding of translation initiation is far from comprehensive and that prior
      conclusions concerning the origin of the process are wrong. Contrary to earlier
      conclusions, key elements of translation initiation originated at the Universal
      Ancestor stage, for homologous counterparts exist in all three primary taxa.
      Herein, we explore the evolutionary relationships among the components of
      bacterial initiation factor 2 (IF-2) and eukaryotic IF-2 (eIF-2)/eIF-2B, i.e.,
      the initiation factors involved in introducing the initiator tRNA into the
      translation mechanism and performing the first step in the peptide chain
      elongation cycle. All Archaea appear to posses a fully functional eIF-2 molecule,
      but they lack the associated GTP recycling function, eIF-2B (a five-subunit
      molecule). Yet, the Archaea do posses members of the gene family defined by the
      (related) eIF-2B subunits alpha, beta, and delta, although these are not
      specifically related to any of the three eukaryotic subunits. Additional members
      of this family also occur in some (but by no means all) Bacteria and even in some
      eukaryotes. The functional significance of the other members of this family is
      unclear and requires experimental resolution. Similarly, the occurrence of
      bacterial IF-2-like molecules in all Archaea and in some eukaryotes further
      complicates the picture of translation initiation. Overall, these data lend
      further support to the suggestion that the rudiments of translation initiation
      were present at the Universal Ancestor stage.

PMID- 9520435
TI  - Data transferability from model organisms to human beings: insights from the
      functional genomics of the flightless region of Drosophila.
AB  - At what biological levels are data from single-celled organisms akin to a Rosetta
      stone for multicellular ones? To examine this question, we characterized a
      saturation-mutagenized 67-kb region of the Drosophila genome by gene deletions,
      transgenic rescues, phenotypic dissections, genomic and cDNA sequencing, bio
      informatic analysis, reverse transcription-PCR studies, and evolutionary
      comparisons. Data analysis using cDNA/genomic DNA alignments and bio-informatic
      algorithms revealed 12 different predicted proteins, most of which are absent
      from bacterial databases, half of which are absent from Saccharomyces cerevisiae,
      and nearly all of which have relatives in Caenorhabditis elegans and Homo
      sapiens. Gene order is not evolutionarily conserved; the closest relatives of
      these genes are scattered throughout the yeast, nematode, and human genomes. Most
      gene expression is pleiotropic, and deletion studies reveal that a morphological
      phenotype is seldom observed when these genes are removed from the genome. These
      data pinpoint some general bottlenecks in functional genomics, and they reveal
      the acute emerging difficulties with data transferability above the levels of
      genes and proteins, especially with complex human phenotypes. At these higher
      levels the Rosetta stone analogy has almost no applicability. However, newer
      transgenic technologies in Drosophila and Mus, combined with coherency pattern
      analyses of gene networks, and synthetic neural modeling, offer insights into
      organismal function. We conclude that industrially scaled robogenomics in model
      organisms will have great impact if it can be realistically linked to epigenetic
      analyses of human variation and to phenotypic analyses of human diseases in
      different genetic backgrounds.

PMID- 9520436
TI  - Developmental rescue of Drosophila cephalic defects by the human Otx genes.
AB  - The molecular mechanisms of head development are a central question in vertebrate
      and invertebrate developmental biology. The anteriorly expressed homeobox gene
      otd in Drosophila and its homolog Otx in mouse are required for the early
      development of the most anterior part of the body, suggesting that a fundamental
      genetic program of cephalic development might be conserved between vertebrates
      and invertebrates. We have examined this hypothesis by introducing the human Otx
      genes into flies. By inducing expression of the human Otx homologs with a heat
      shock promoter, we found that both Otx1 and Otx2 functionally complement the
      cephalic defects of a fly otd mutant through specific activation and inactivation
      of downstream genes. Combined with previous morphological studies, these results
      are consistent with the view that a common molecular ground plan of cephalization
      was invented before the diversification of the protostome and the deuterostome in
      the course of metazoan evolution.

PMID- 9520437
TI  - Stable transformation of the yellow fever mosquito, Aedes aegypti, with the
      Hermes element from the housefly.
AB  - The mosquito Aedes aegypti is the world's most important vector of yellow fever
      and dengue viruses. Work is currently in progress to control the transmission of
      these viruses by genetically altering the capacity of wild Ae. aegypti
      populations to support virus replication. The germ-line transformation system
      reported here constitutes a major advance toward the implementation of this
      control strategy. A modified Hermes transposon carrying a 4.7-kb fragment of
      genomic DNA that includes a wild-type allele of the Drosophila melanogaster
      cinnabar (cn) gene was used to transform a white-eyed recipient strain of Ae.
      aegypti. Microinjection of preblastoderm mosquito embryos with this construct
      resulted in 50% of the emergent G0 adults showing some color in their eyes. Three
      transformed families were recovered, each resulting from an independent insertion
      event of the cn+-carrying transposon. The cn+ gene functioned as a semidominant
      transgene and segregated in Mendelian ratios. Hermes shows great promise as a
      vector for efficient, heritable, and stable transformation of this important
      mosquito vector species.

PMID- 9520438
TI  - Mariner transposition and transformation of the yellow fever mosquito, Aedes
      aegypti.
AB  - The mariner transposable element is capable of interplasmid transposition in the
      embryonic soma of the yellow fever mosquito, Aedes aegypti. To determine if this
      demonstrated mobility could be utilized to genetically transform the mosquito, a
      modified mariner element marked with a wild-type allele of the Drosophila
      melanogaster cinnabar gene was microinjected into embryos of a kynurenine
      hydroxylase-deficient, white-eyed recipient strain. Three of 69 fertile male
      founders resulting from the microinjected embryos produced families with colored
      eyed progeny individuals, a transformation rate of 4%. The transgene-mediated
      complementation of eye color was observed to segregate in a Mendelian manner,
      although one insertion segregates with the recessive allele (female-determining)
      of the sex-determining locus, and a separate insertion is homozygous lethal.
      Molecular analysis of selected transformed families demonstrated that a single
      complete copy of the construct had integrated independently in each case and that
      it had done so in a transposase-mediated manner. The availability of a mariner
      transformation system greatly enhances our ability to study and manipulate this
      important vector species.

PMID- 9520439
TI  - Parallel analysis of genetic selections using whole genome oligonucleotide
      arrays.
AB  - Thousands of genes have recently been sequenced in organisms ranging from
      Escherichia coli to human. For the majority of these genes, however, available
      sequence does not define a biological role. Efficient functional characterization
      of these genes requires strategies for scaling genetic analyses to the whole
      genome level. Plasmid-based library selections are an established approach to the
      functional analysis of uncharacterized genes and can help elucidate biological
      function by identifying, for example, physical interactors for a gene and genetic
      enhancers and suppressors of mutant phenotypes. The application of these
      selections to every gene in a eukaryotic genome, however, is generally limited by
      the need to manipulate and sequence hundreds of DNA plasmids. We present an
      alternative approach in which identification of nucleic acids is accomplished by
      direct hybridization to high-density oligonucleotide arrays. Based on the
      complete sequence of Saccharomyces cerevisiae, high-density arrays containing
      oligonucleotides complementary to every gene in the yeast genome have been
      designed and synthesized. Two-hybrid protein-protein interaction screens were
      carried out for S. cerevisiae genes implicated in mRNA splicing and microtubule
      assembly. Hybridization of labeled DNA derived from positive clones is sufficient
      to characterize the results of a screen in a single experiment, allowing rapid
      determination of both established and previously unknown biological interactions.
      These results demonstrate the use of oligonucleotide arrays for the analysis of
      two-hybrid screens. This approach should be generally applicable to the analysis
      of a range of genetic selections.

PMID- 9520440
TI  - Overlapping roles and asymmetrical cross-regulation of the USF proteins in mice.
AB  - USF1 and USF2 are ubiquitously expressed transcription factors implicated as
      antagonists of the c-Myc protooncoprotein in the control of cellular
      proliferation. To determine the biological role of the USF proteins, mutant mice
      were generated by homologous recombination in embryonic stem cells. USF1-null
      mice were viable and fertile, with only slight behavioral abnormalities. However,
      these mice contained elevated levels of USF2, which may compensate for the
      absence of USF1. In contrast, USF2-null mice contained reduced levels of USF1 and
      displayed an obvious growth defect: they were 20-40% smaller at birth than their
      wild-type or heterozygous littermates and maintained a smaller size with
      proportionate features throughout postnatal development. Some of the USF
      deficient mice, especially among the females, were prone to spontaneous epileptic
      seizures, suggesting that USF is important in normal brain function. Among the
      double mutants, an embryonic lethal phenotype was observed for mice that were
      homozygous for the Usf2 mutation and either heterozygous or homozygous for the
      Usf1 mutation, demonstrating that the USF proteins are essential in embryonic
      development.

PMID- 9520441
TI  - Rapid isolation of cDNA by hybridization.
AB  - The isolation of genes from a given genomic region can be a rate-limiting step in
      the discovery of disease genes. We describe an approach to the isolation of cDNAs
      that have sequences in common with large genomic clones such as bacterial
      artificial chromosomes. We applied this method to loci both amplified and deleted
      in cancer, illustrating its usage in the identification of both oncogenes and
      tumor suppressor genes, respectively. The method, called rapid isolation of cDNAs
      by hybridization (RICH), depends on solution hybridization, enzymatic
      modification, and amplification/selection of sequences present in both cDNA
      populations and the genomic clones. The method should facilitate the development
      of transcription maps for large genomic clones, possibly even yeast artificial
      chromosomes.

PMID- 9520442
TI  - Unusual features of the Drosophila melanogaster telomere transposable element HeT
      A are conserved in Drosophila yakuba telomere elements.
AB  - HeT-A was the first transposable element shown to have a bona fide role in
      chromosome structure, maintenance of telomeres in Drosophila melanogaster. HeT-A
      has hallmarks of non-long-terminal-repeat (non-LTR) retrotransposable elements
      but also has several unique features. We have now isolated HeT-A elements from
      Drosophila yakuba, showing that the retrotransposon mechanism of telomere
      maintenance predates the separation of D. melanogaster and D. yakuba (5-15
      million years ago). HeT-A elements from the two species show significant sequence
      divergence, yet unusual features seen in HeT-Amel are conserved in HeT-Ayak. In
      both species, HeT-A elements are found in head-to-tail tandem arrays in telomeric
      heterochromatin. In both species, nearly half of the HeT-A sequence is noncoding
      and shows a distinctive imperfect repeat pattern of A-rich segments. Neither
      element encodes reverse transcriptase. The HeT-Amel promoter appears to be
      intermediate between the promoters of non-LTR and of LTR retrotransposons. The
      HeT-Ayak promoter shows similar features. HeT-Amel has a frameshift within the
      coding region. HeT-Ayak does not require a frameshift but shows conservation of
      the polypeptide sequence of the frameshifted product of D. melanogaster.

PMID- 9520443
TI  - Probing the genetic population structure of Trypanosoma cruzi with polymorphic
      microsatellites.
AB  - We describe here the identification of eight polymorphic microsatellite loci with
      (CA)n repeats in the Trypanosoma cruzi genome based on the affinity capture of
      fragments using biotinylated (CA)12 attached to streptavidin-coated magnetic
      beads. The presence of two peaks in PCR amplification products from individual
      clones confirmed that T. cruzi is diploid. Hardy-Weinberg and linkage
      disequilibrium analyses suggested that sexual reproduction is rare or absent and
      that the population structure is clonal. Several strains, especially those
      isolated from nonhuman sources, showed more than two alleles in many loci
      demonstrating that they were multiclonal. The phylogenetic analysis of T. cruzi
      based on microsatellites revealed a great genetic distance among strains,
      although the strain dispersion profile in the Wagner network was in general
      agreement with the species dimorphism found by PCR amplification of the divergent
      region of the rRNA 24Salpha gene.

PMID- 9520444
TI  - Molecular anatomy of chromosome 7q deletions in myeloid neoplasms: evidence for
      multiple critical loci.
AB  - Complete or partial deletions of the long arm of chromosome 7 (7q- and -7) are
      nonrandom abnormalities seen in primary and therapy-induced myelodysplasia (MDS)
      and acute myelogenous leukemia (AML). Monosomy 7, occurring as the sole
      cytogenetic anomaly in a small but significant number of cases, may denote a
      dominant mechanism involving critical tumor suppressor gene(s). We have
      determined the extent of allele loss in cytogenetically prescreened MDS and AML
      patients for microsatellite markers from chromosome 7q22 and 7q31. Whereas >80%
      of these cases revealed allele loss for the entire region, a rare case of the 7q-
      chromosome showed allele loss for only the proximal 7q31.1 loci flanked by the
      markers D7S486 and D7S2456, and a case of monosomy 7 revealed allele loss for
      loci at both 7q31 and 7q22 with retention of sequences between these sets of
      loci. Furthermore, a case of AML with no cytogenetic anomaly of chromosome 7
      revealed a submicroscopic allelic imbalance for a third distal locus, D7S677.
      These findings suggest the presence of three distinct critical loci that may
      contribute alone or in combination to the evolution of MDS and AML. The data also
      provide molecular evidence for unbalanced translocation with noncontiguous
      deletions, as an alternate mechanism underlying monosomy 7.

PMID- 9520445
TI  - A third distinct tumor necrosis factor receptor of orthopoxviruses.
AB  - Cowpox virus Brighton red strain (CPV) contains a gene, crmD, which encodes a 320
      aa tumor necrosis factor receptor (TNFR) of 44% and 22% identity, respectively,
      to the CPV TNFR-like proteins, cytokine response modifiers (crm) CrmB and CrmC.
      The crmD gene was interrupted in three other cowpox strains examined and absent
      in various other orthopoxviruses; however, four strains of ectromelia virus (ECT)
      examined contained an intact crmD (97% identity to CPV crmD) and lacked cognates
      of crmB and crmC. The protein, CrmD, contains a transport signal; a 151-aa
      cysteine-rich region with 21 cysteines that align with human TNFRII ligand
      binding region cysteines; and C-terminal region sequences that are highly
      diverged from cellular TNFR C-terminal region sequences involved in signal
      transduction. Bacterial maltose-binding proteins containing the CPV or ECT CrmD
      cysteine-rich region bound TNF and lymphotoxin-alpha (LTalpha) and blocked their
      in vitro cytolytic activity. Secreted viral CrmD bound TNF and LTalpha and was
      detectable after the early stage of replication, using nonreducing conditions, as
      60- to 70-kDa predominant and 90- to 250-kDa minor disulfide-linked complexes
      that were able to be reduced to a 46-kDa form and deglycosylated to a 38-kDa
      protein. Cells infected with CPV produced extremely low amounts of CrmD compared
      with ECT. Possessing up to three TNFRs, including CrmD, which is secreted as
      disulfide-linked complexes in varied amounts by CPV and ECT, likely enhances the
      dynamics of the immune modulating mechanisms of orthopoxviruses.

PMID- 9520446
TI  - NF-kappaB-inducing kinase activates IKK-alpha by phosphorylation of Ser-176.
AB  - Activation of the transcription factor NF-kappaB by inflammatory cytokines
      involves the successive action of NF-kappaB-inducing kinase (NIK) and two IkappaB
      kinases, IKK-alpha and IKK-beta. Here we show that NIK preferentially
      phosphorylates IKK-alpha over IKK-beta, leading to the activation of IKK-alpha
      kinase activity. This phosphorylation of IKK-alpha occurs specifically on Ser-176
      in the activation loop between kinase subdomains VII and VIII. A mutant form of
      IKK-alpha containing alanine at residue 176 cannot be phosphorylated or activated
      by NIK and acts as a dominant negative inhibitor of interleukin 1- and tumor
      necrosis factor-induced NF-kappaB activation. Conversely, a mutant form of IKK
      alpha containing glutamic acid at residue 176 is constitutively active. Thus, the
      phosphorylation of IKK-alpha on Ser-176 by NIK may be required for cytokine
      mediated NF-kappaB activation.

PMID- 9520447
TI  - Natural killer activating receptors trigger interferon gamma secretion from T
      cells and natural killer cells.
AB  - Proliferation of human CD4+ alphabeta T cells expressing a natural killer cell
      activating receptor (NKAR) has been shown to be enhanced, particularly in
      response to low doses of antigen, if the target cells present appropriate human
      class I major histocompatibility complex (MHC) molecules. Here, we show that NKAR
      also enhance proliferation and killing of target cells by subsets of CD8+
      alphabeta and CD8+ gammadelta T cells, as well as by NK cells. Strikingly,
      interferon gamma secretion from all of these types of lymphocytes was markedly
      increased by interaction of the NKAR with their MHC class I ligands,
      independently of enhancement of proliferation. Thus, the recognition of class I
      MHC molecules by NKAR on both T cells and NK cells may provide a regulatory
      mechanism that affects immune responses through the secretion of interferon gamma
      and possibly other cytokines. It represents a signal for cytokine secretion
      alternative and/or augmentative to that through the T cell receptor.

PMID- 9520448
TI  - The role of peptides in thymic positive selection of class II major
      histocompatibility complex-restricted T cells.
AB  - A thymic epithelial cell line transfected with I-Ek was used in reaggregate
      cultures to study the role of peptides in positive selection of T cell receptor
      transgenic thymocytes. In this system, positive selection of CD4 SP cells
      occurred only after the addition of exogenous peptide. Analysis of antigen
      analogs indicated an inverse relationship between the antigenicity for peripheral
      T cells and the concentration of peptide required for positive selection. These
      data are most consistent with an avidity (rather than an affinity) model of
      positive selection, in which ligand density and the affinity of T cell receptor
      act in concert to determine the fate of developing thymocytes.

PMID- 9520449
TI  - Cytokine-induced survival of activated T cells in vitro and in vivo.
AB  - Many antigen-specific T cells die after exposure to antigen in animals. These
      cells also die if they are isolated from animals shortly after activation and
      cultured. Various cytokines were tested for their ability to interfere with this
      in vitro death. Surprisingly, tumor necrosis factor alpha and other inflammatory
      cytokines did not prevent the in vitro death of activated T cells, even though
      these cytokines do prevent activated T cell death in animals. Therefore, the
      inflammatory cytokines probably act on T cells in vivo via an intermediary
      factor. Four cytokines, interleukin (IL)-2, IL-4, IL-7, and IL-15, did prevent
      activated T cell death in vitro, with IL-4 and IL-15 more effective than IL-2 or
      IL-7. These cytokines share a component of their receptors, the common gamma
      chain, gammac. Therefore, their collective ability to protect activated T cells
      from death may be mediated by signals involving gammac. To assess their activity
      in vivo, two of the cytokines, IL-2 and IL-4, were expressed in animals at local
      sites of superantigen responses. Both cytokines increased the numbers of T cells
      found at the local sites 14 days later. Interleukin 4 was more effective than IL
      2, even though IL-2 stimulates T cell proliferation better than IL-4. This result
      suggested that IL-4 and related cytokines can promote T cell survival in vivo as
      well as in vitro. The ability of these cytokines to prevent the death of
      activated T cells may be important at certain stages of immune responses in
      animals.

PMID- 9520450
TI  - High affinity cross-reacting mAb generated by minimal mimicry: implications for
      the pathogenesis of anti-nuclear autoantibodies and immunosuppression.
AB  - The antigen recognition of a profoundly immunosuppressive mAb, mAb 2E1, in vivo
      was investigated. In addition to the 62-kDa effector cell protease receptor 1,
      mAb 2E1 bound the 32-kDa T cell adhesion receptor E2 (CD99) and the 86-kDa p80
      subunit of the nuclear antigen complex Ku. These molecules share no overall
      sequence similarity. Peptide mapping experiments identified the mAb 2E1 cross
      reacting epitopes as the sequences 66GSFSDADLAD75 in E2 and 571GGAHFSVSSLAEG583
      in p80 of Ku, sharing a minimal homology motif FSXXXLA, in which X is a
      nonconserved amino acid. Each of these peptides separately inhibited the binding
      of mAb 2E1 to E2, effector cell protease receptor 1, and p80 of Ku in a dose
      dependent manner. Scatchard plot analysis of 125I-labeled mAb 2E1 binding to
      peripheral blood mononuclear cells revealed a high-affinity interaction with a
      dissociation constant of 7 x 10(-10) M. An anti-E2 mAb bound the same epitope
      66GSFSDADLAD75 recognized by mAb 2E1 but failed to react with p80 of Ku and was
      not immunosuppressive. These findings demonstrate that high-affinity cross
      reacting mAbs can be generated by mimicry of a minimal surface on unrelated
      molecules. This model of minimal mimicry may determine the nuclear reactivity of
      certain autoantibodies to Ku and contribute to aberrant immunosuppression in
      vivo.

PMID- 9520451
TI  - Antibody-mediated targeting of CD45 isoforms: a novel immunotherapeutic strategy.
AB  - CD45 is a family of transmembrane protein tyrosine phosphatases exclusively
      expressed by hematopoietic cells and critically involved in the regulation of T
      cell activation signals. We now demonstrate that three 100-microg doses of anti
      CD45RB mAb MB23G2 can induce long-term engraftment of islets into major
      histcompatibility complex-disparate chemically diabetic mice. Long-term graft
      survivors (>120 days) were tolerant to new islet allografts from the original
      donor strain. MB23G2 induced a temporary decrease in number circulating
      leukocytes but had no effect on leukocyte number in other lymphoid compartments.
      Histologic examination of allografts from treated and untreated recipients
      revealed a similar peri-islet infiltration on day 6. Eleven days after
      transplant, the peri-islet infiltrate in treated animals persisted, but in marked
      contrast to untreated control animals, there was no insulitis and islet integrity
      was preserved. The peri-islet infiltrate from treated animals showed a mild
      increase in CD4 cells, a decrease in CD8 cells, and decreased intensity of CD45RB
      expression. Treatment of naive animals with anti-CD45RB (MB23G2) resulted in a
      shift in CD45 isoform expression on T cells with a loss of higher molecular
      weight isoforms and increased expression of lower molecular weight (CD45R0)
      isoform. This shift in CD45 isoform expression from CD45RBHi to CD45RBLo was
      associated with an increase in the intragraft expression of transcripts for
      interleukin (IL) 4 and IL-10, consistent with the expected activity of this
      distinct immunoregulatory T cell subset. Antibody-mediated targeting of CD45 may
      induce tolerance through novel mechanisms and have direct applicability to
      clinical transplantation in humans.

PMID- 9520452
TI  - The Tpl-2 protooncoprotein activates the nuclear factor of activated T cells and
      induces interleukin 2 expression in T cell lines.
AB  - Tpl-2 expression is induced within 30-60 min after ConA stimulation of rat
      splenocytes, suggesting that it may contribute to the induction of IL-2 during T
      cell activation. Herein we show that wild-type and carboxyl-terminally truncated
      (activated) Tpl-2 activate the nuclear factor of activated T cells (NFAT) and
      induce interleukin 2 (IL-2) expression in EL4 cells. In Jurkat cells the
      truncated Tpl-2 activates NFAT and induces IL-2, whereas wild-type Tpl-2
      activates NFAT only when cotransfected with NFAT expression constructs,
      suggesting that Tpl-2 may induce NFAT activation signals. Experiments in NIH 3T3
      cells revealed that the NFATp isoform, but not the NFATc or NFATx isoform,
      undergoes nuclear translocation when coexpressed with wild-type Tpl-2 and
      confirmed this hypothesis. Activation of NFAT by anti-CD3 stimulation but not by
      phorbol 12-myristate 13-acetate and ionomycin in Jurkat cells was inhibited by
      the kinase-dead Tpl-2K167M, suggesting that Tpl-2 contributes to the transduction
      of NFAT activation signals originating in the T cell receptor. The Tpl-2-mediated
      induction of IL-2 was not observed in T cell lymphoma lines other than EL4 and
      Jurkat, as well as in normal T cells. NFAT activation by Tpl-2, however, was
      observed in several cell lines including some of nonhematopoietic origin. The
      activation of NFAT by Tpl-2 in different cell types defines a molecular mechanism
      that may contribute to its oncogenic potential.

PMID- 9520453
TI  - T cell epitopes of insulin defined in HLA-DR4 transgenic mice are derived from
      preproinsulin and proinsulin.
AB  - Approximately one-half of Caucasians with newly diagnosed insulin-dependent
      diabetes mellitus (IDDM) have autoantibodies to insulin, and the majority of
      those express the HLA-DR4 genotype [Ziegler, R., Alper, C. A., Awdeh, Z. L.,
      Castano, L., Brink, S. J., Soeldner, J. S., Jackson, R. A. & Eisenbarth, G. S.
      (1991) Diabetes 40, 709-714]. However, it has been difficult to demonstrate T
      cell proliferative responses to human insulin in IDDM patients [Durinovic-Bello,
      I., Hummel, M. & Ziegler, A. G. (1996) Diabetes 45, 795-800]. We have immunized
      transgenic mice expressing the susceptible HLA-DR (alpha1*0101,beta1*0401)
      (hereafter called DRB1*0401) and human CD4 molecules on a murine major
      histocompatibility complex class II null background, with human preproinsulin
      (PPI), proinsulin (PI), and insulin and derived large panels of T cell hybridomas
      to determine the immunogenic epitopes of these proteins. These results show that
      the prohormones PI or PPI carry the major immunogenic T cell epitope in the
      DRB1*0401 transgenic mice. The PPI/PI immunodominant epitope LALEGSLQK was
      localized at the C-peptide/A-chain junction. This T cell epitope PPI/PI LALEGSLQK
      is unusual because, normally, it is proteolytically destroyed during the
      maturation of the insulin molecule. Additionally, this T cell epitope is both
      processed and presented by human DRB1*0401-positive Epstein-Barr virus
      transformed B cells, and it can also stimulate T cells from the peripheral blood
      of HLA-DR4-positive patients with type 1 diabetes. These findings may partly
      explain why susceptibility to type 1 diabetes is associated with HLA-DR4-positive
      individuals and why T cell responses to the mature insulin protein are rarely
      detected in IDDM patients.

PMID- 9520454
TI  - A conserved sequence block in murine and human T cell receptor (TCR) Jalpha
      region is a composite element that enhances TCR alpha enhancer activity and binds
      multiple nuclear factors.
AB  - A conserved sequence block (CSB) located in a noncoding region of the mouse and
      human TCR alpha/delta loci, showing six differences over 125 nucleotide positions
      (95% similar), was subjected to detailed analyses in this study. Transient
      transfection results showed that the CSB-containing element in conjunction with
      the TCR alpha enhancer up-regulated the alpha enhancer activity, whereas no
      enhancer activity was detected when CSB alone was assayed. In vitro occupancy
      analyses of CSB by nuclear factors reveal the existence of an unexpectedly
      intricate network of CSB-protein and protein-protein interactions. Lymphoid
      specific as well as T-lineage-specific nuclear factors are involved to
      differentially form CSB-bound complexes in extracts of various tissues and cell
      lines. Liver was shown to contain factor(s) sequestering thymic CSB-binding
      factors. Furthermore, the putative binding sites for transcription factors known
      to be important for lymphoid-lineage development are present in CSB and are
      targeted by nuclear factors. On the basis of these results, we propose that the
      CSB element may play a role in shaping the chromatin structure by which the
      accessibility of TCR alpha/delta loci to the recombinase complex and/or to the
      transcriptional apparatus can be controlled.

PMID- 9520455
TI  - Recruitment of SH2-containing protein tyrosine phosphatase SHP-1 to the
      interleukin 2 receptor; loss of SHP-1 expression in human T-lymphotropic virus
      type I-transformed T cells.
AB  - Interleukin 2 (IL-2) rapidly induces tyrosine phosphorylation of intracellular
      substrates, including the IL-2 receptor beta chain (IL-2Rbeta), Janus kinase 1
      (Jak1), Jak3, signal transducer/activator of transcription proteins, and Shc, but
      the mechanism underlying dephosphorylation of these proteins is not known. The
      src homology 2 (SH2) containing tyrosine phosphatase 1 (SHP-1) is recruited by
      several hematopoietic surface receptors indicating that this phosphatase plays an
      important role as a regulator of signaling. We have found that IL-2 induces
      association of SHP-1 with the IL-2 receptor complex, and that once SHP-1 is
      recruited to the activated receptor it is able to decrease tyrosine
      phosphorylation of IL-2Rbeta and the associated tyrosine kinases Jak1 and Jak3.
      This dephosphorylation is specific as expression of a catalytically inactive form
      of SHP-1, or expression of the related phosphatase SHP-2 did not result in
      dephosphorylation of the IL-2 receptor components. Furthermore, we have found
      that SHP-1 expression is greatly decreased or undetectable in a number of IL-2
      independent HTLV-I transformed T cell lines that exhibit constitutive Jak/signal
      transducer/activator of transcription activation. In HTLV-I infected T cells,
      down-regulation of SHP-1 expression was also found to correlate with the
      acquisition of IL-2 independence. These observations suggest that SHP-1 normally
      functions to antagonize the IL-2 signal transduction pathway and that HTLV-I
      infection and oncogenic transformation can lead to loss of SHP-1 expression
      resulting in constitutive activation of IL-2 regulated T cell responses.

PMID- 9520456
TI  - Interferon alpha and Tat involvement in the immunosuppression of uninfected T
      cells and C-C chemokine decline in AIDS.
AB  - HIV type 1 (HIV-1) not only directly kills infected CD4(+) T cells but also
      induces immunosuppression of uninfected T cells. Two immunosuppressive proteins,
      interferon alpha (IFNalpha) and extracellular Tat, mediate this process because
      specific antibodies against these proteins prevent generation of suppressor cells
      in HIV-1-infected peripheral blood mononuclear cell cultures. Furthermore, the
      production of C-C chemokines in response to immune cell activation, initially
      enhanced by IFNalpha and Tat, ultimately is inhibited by these proteins in
      parallel with their induction of immunosuppression. The clinical corollary is the
      immunosuppression of uninfected T cells and the decline in C-C chemokine release
      found at advanced stages of HIV-1 infection paralleling rising levels of IFNalpha
      and extracellular Tat. We, therefore, suggest that IFNalpha and Tat may be
      critical targets for anti-AIDS strategies.

PMID- 9520457
TI  - C-C chemokines, pivotal in protection against HIV type 1 infection.
AB  - Exposure to HIV type 1 (HIV-1) does not usually lead to infection. Although this
      could be because of insufficient virus titer, there is now abundant evidence that
      some individuals resist infection even when directly exposed to a high titer of
      HIV. This protection recently has been correlated with homozygous mutations of an
      HIV-1 coreceptor, namely CCR5, the receptor for the beta-chemokines. Moreover,
      earlier results already had shown that the same chemokines markedly suppress the
      nonsyncitial inducing variants of HIV-1, the chief virus type transmitted from
      person to person. CCR5 mutation, as a unique mechanism of protection, is,
      however, suspect because HIV-1 variants can use other chemokine receptors as
      their coreceptor. Moreover, recent results have established that infection can
      indeed sometimes occur with such mutations. Here, we report on transient natural
      resistance over time of most of 128 hemophiliacs who were inoculated repeatedly
      with HIV-1-contaminated Factor VIII concentrate from plasma during 1980-1985
      before the development of the HIV blood test. Furthermore, and remarkably, 14
      subjects remain uninfected to this date, and in these subjects we found
      homozygous CCR5 mutations in none but in most of them overproduction of beta
      chemokines. In vitro experiments confirmed the potent anti-HIV suppressive effect
      of these chemokines.

PMID- 9520458
TI  - An X chromosome gene regulates hematopoietic stem cell kinetics.
AB  - Females are natural mosaics for X chromosome-linked genes. As X chromosome
      inactivation occurs randomly, the ratio of parental phenotypes among blood cells
      is approximately 1:1. Recently, however, ratios of greater than 3:1 have been
      observed in 38-56% of women over age 60. This could result from a depletion of
      hematopoietic stem cells (HSCs) with aging (and the maintenance of hematopoiesis
      by a few residual clones) or from myelodysplasia (the dominance of a neoplastic
      clone). Each possibility has major implications for chemotherapy and for
      transplantation in elderly patients. We report similar findings in longitudinal
      studies of female Safari cats and demonstrate that the excessive skewing that
      develops with aging results from a third mechanism that has no pathologic
      consequence, hemizygous selection. We show that there is a competitive advantage
      for all HSCs with a specific X chromosome phenotype and, thus, demonstrate that
      an X chromosome gene (or genes) regulates HSC replication, differentiation,
      and/or survival.

PMID- 9520459
TI  - Protection against peroxynitrite-induced fibroblast injury and arthritis
      development by inhibition of poly(ADP-ribose) synthase.
AB  - Peroxynitrite, a cytotoxic oxidant formed from nitric oxide (NO) and superoxide,
      induces DNA strand breakage, which activates the nuclear enzyme poly(ADP-ribose)
      synthase (PARS; EC 2.4.2.30). The cellular function of PARS was determined in
      fibroblast lines from PARS knockout animals (PARS-/-) and corresponding wild-type
      animals (PARS+/+), with the aid of the lipophilic PARS inhibitor 5-iodo-6-amino
      1,2-benzopyrone (INH2BP). We investigated the role of PARS in peroxynitrite
      induced fibroblast injury in vitro and also in the development of arthritis in
      vivo. Exposure of embryonic fibroblasts from the PARS+/+ animals to peroxynitrite
      caused DNA single-stand breakage and PARS activation and caused an acute
      suppression of mitochondrial respiration. INH2BP protected the PARS+/+ cells
      against the suppression of mitochondrial respiration in response to peroxynitrite
      (50-100 microM). Similarly to PARS inhibition with INH2BP, the PARS-/- cells were
      protected against peroxynitrite-induced injury. The protection against cellular
      injury by PARS-/- phenotype or INH2BP waned when cells were challenged with
      higher concentrations of the oxidant. Inhibition of PARS by INH2BP or by PARS-/-
      phenotype reduced inducible nitric-oxide synthase (iNOS; EC 1.14.13.39) mRNA
      levels and inhibited production of NO in immunostimulated cells. INH2BP had no
      peroxynitrite scavenging or hydroxyl radical scavenging effects, and it exerted
      no additional (nonspecific) effects in the PARS-/- cells. In collagen-induced
      arthritis, significant staining for nitrotyrosine, a marker of peroxynitrite
      formation, was found in the inflamed joints. Oral treatment with INH2BP (0.5
      g/kg, daily), starting at the onset of arthritis (day 25), delayed the
      development of the clinical signs at days 26-35 and improved histological status
      in the knee and paw. Our data demonstrate that deletion of PARS by genetic
      manipulation or pharmacological inhibition of PARS protects against oxidant
      induced cellular injury in vitro and exhibits anti-inflammatory effects in vivo.

PMID- 9520461
TI  - Analysis of ClC-2 channels as an alternative pathway for chloride conduction in
      cystic fibrosis airway cells.
AB  - Cystic fibrosis (CF) is a lethal inherited disease that results from abnormal
      chloride conduction in epithelial tissues. ClC-2 chloride channels are expressed
      in epithelia affected by CF and may provide a key "alternative" target for
      pharmacotherapy of this disease. To explore this possibility, the expression
      level of ClC-2 channels was genetically manipulated in airway epithelial cells
      derived from a cystic fibrosis patient (IB3-1). Whole-cell patch-clamp analysis
      of cells overexpressing ClC-2 identified hyperpolarization-activated Cl- currents
      (HACCs) that displayed time- and voltage-dependent activation, and an inwardly
      rectifying steady-state current-voltage relationship. Reduction of extracellular
      pH to 5.0 caused significant increases in HACCs in overexpressing cells, and the
      appearance of robust currents in parental IB3-1 cells. IB3-1 cells stably
      transfected with the antisense ClC-2 cDNA showed reduced expression of ClC-2
      compared with parental cells by Western blotting, and a significant reduction in
      the magnitude of pH-dependent HACCs. To determine whether changes in
      extracellular pH alone could initiate chloride transport via ClC-2 channels, we
      performed 36Cl- efflux studies on overexpressing cells and cells with endogenous
      expression of ClC-2. Acidic extracellular pH increased 36Cl- efflux rates in both
      cell types, although the ClC-2 overexpressing cells had significantly greater
      chloride conduction and a longer duration of efflux than the parental cells.
      Compounds that exploit the pH mechanism of activating endogenous ClC-2 channels
      may provide a pharmacologic option for increasing chloride conductance in the
      airways of CF patients.

PMID- 9520460
TI  - Transcriptional map of 170-kb region at chromosome 11p15.5: identification and
      mutational analysis of the BWR1A gene reveals the presence of mutations in tumor
      samples.
AB  - Chromosome region 11p15.5 harbors unidentified genes involved in neoplasms and in
      the genetic disease Beckwith-Wiedemann syndrome. The genetic analysis of a 170-kb
      region at 11p15.5 between loci D11S601 and D11S679 resulted in the identification
      of six transcriptional units. Three genes, hNAP2, CDKN1C, and KVLQT1, are well
      characterized, whereas three genes are novel. The three additional genes were
      designated BWR1A, BWR1B, and BWR1C. Full-length cDNAs for these three genes were
      cloned and nucleotide sequences were determined. While our work was in progress,
      BWR1C cDNA was described as IPL [Qian, N., Franck, D., O'Keefe, D., Dao, D. ,
      Zhao, L., Yuan, L., Wang, Q., Keating, M., Walsh, C. & Tycko, B. (1997) Hum. Mol.
      Genet. 6, 2021-2029]. The cloning and mapping of these genes together with the
      fine mapping of the three known genes indicates that the transcriptional map of
      this region is likely to be complete. Because this region frequently is altered
      in neoplasms and in the genetic disease Beckwith-Wiedemann syndrome, we carried
      out a mutational analysis in tumor cell lines and Beckwith-Wiedemann syndrome
      samples that resulted in the identification of genetic alterations in the BWR1A
      gene: an insertion that introduced a stop codon in the breast cancer cell line
      BT549 and a point mutation in the rhabdomyosarcoma cell line TE125-T. These
      results indicate that BWR1A may play a role in tumorigenesis.

PMID- 9520462
TI  - Deregulated expression of TCL1 causes T cell leukemia in mice.
AB  - The TCL1 oncogene on human chromosome 14q32.1 is involved in the development of T
      cell leukemia in humans. These leukemias are classified either as T
      prolymphocytic leukemias, which occur very late in life, or as T chronic
      lymphocytic leukemias, which often arise in patients with ataxia telangiectasia
      (AT) at a young age. The TCL1 oncogene is activated in these leukemias by
      juxtaposition to the alpha or beta locus of the T cell receptor, caused by
      chromosomal translocations t(14:14)(q11:q32), t(7:14)(q35:q32), or by inversions
      inv(14)(q11:q32). To show that transcriptional alteration of TCL1 is causally
      involved in the generation of T cell neoplasia we have generated transgenic mice
      that carry the TCL1 gene under the transcriptional control of the p56(lck)
      promoter element. The lck-TCL1 transgenic mice developed mature T cell leukemias
      after a long latency period. Younger mice presented preleukemic T cell expansions
      expressing TCL1, and leukemias developed only at an older age. The phenotype of
      the murine leukemias is CD4-CD8+, in contrast to human leukemias, which are
      predominantly CD4+CD8-. These studies demonstrate that transcriptional activation
      of the TCL1 protooncogene can cause malignant transformation of T lymphocytes,
      indicating the role of TCL1 in the initiation of malignant transformation in T
      prolymphocytic leukemias and T chronic lymphocytic leukemias.

PMID- 9520463
TI  - The T cell leukemia LIM protein Lmo2 is necessary for adult mouse hematopoiesis.
AB  - The LIM-finger protein Lmo2, which is activated in T cell leukemias by
      chromosomal translocations, is required for yolk sac erythropoiesis. Because Lmo2
      null mutant mice die at embryonic day 9-10, it prevents an assessment of a role
      in other stages of hematopoiesis. We have now studied the hematopoietic
      contribution of homozygous mutant Lmo2 -/- mouse embryonic stem cells and found
      that Lmo2 -/- cells do not contribute to any hematopoietic lineage in adult
      chimeric mice, but reintroduction of an Lmo2-expression vector rescues the
      ability of Lmo2 null embryonic stem cells to contribute to all lineages tested.
      This disruption of hematopoiesis probably occurs because interaction of Lmo2
      protein with factors such as Tal1/Scl is precluded. Thus, Lmo2 is necessary for
      early stages of hematopoiesis, and the Lmo2 master gene encodes a protein that
      has a central and crucial role in the hematopoietic development.

PMID- 9520464
TI  - Taxane-mediated gene induction is independent of microtubule stabilization:
      induction of transcription regulators and enzymes that modulate inflammation and
      apoptosis.
AB  - Pharmacological traits of the antineoplastic agent taxol may originate in part
      from its effects on gene expression and not simply from its effects on
      microtubule assembly. This prompts three questions. First, how extensive is gene
      induction by taxol? Second, is gene induction confined to taxol itself, or does
      it occur with other taxane analogs? Third, do the functions of any induced genes
      correspond with known attributes of taxol or taxane analogs? We report that taxol
      induces numerous early-response genes, not just cytokine genes. Previously
      unidentified taxol-induced genes include genes coding transcription factors with
      tumor suppressor effects (krox-24) and enzymes that govern proliferation,
      apoptosis, and inflammation (2'5'-oligoadenylate synthase, cyclooxygenase-2, and
      an IkappaB kinase termed chuk). Taxotere, a potent analog of taxol, did not
      induce any of these genes, implying that taxol modulates gene expression by a
      mechanism that is distinct from microtubule stabilization and cell cycle arrest.
      Other taxane analogs induce some of the same genes as taxol, indicating that this
      process is not unique to taxol. Functional changes coincided with changes in gene
      expression. For instance, induction of tumor necrosis factor alpha (TNFalpha)
      accentuated apoptosis in cells treated with taxol compared with corresponding
      cells treated with taxotere. The functions of several induced genes (e.g., krox
      24 and cyclooxygenase-2) are self-consistent with beneficial and adverse effects
      encountered during taxol administration. These results may be relevant to the
      safe and effective use of taxol or its analogs in oncology and other areas of
      medicine.

PMID- 9520465
TI  - Identification and isolation of candidate human keratinocyte stem cells based on
      cell surface phenotype.
AB  - Despite the central role of human epidermal stem cells in tissue homeostasis,
      wound repair, and neoplasia, remarkably little is known about these cells,
      largely due to the absence of molecular markers that distinguish them from other
      proliferative cells within the germinative/basal layer. Epidermal stem cells can
      be distinguished from other cells in the basal layer by their quiescent nature in
      vivo and their greater overall proliferative capacity. In this study, we
      demonstrate enrichment and isolation of a subpopulation of basal epidermal cells
      from neonatal human foreskin based on cell surface phenotype, which satisfy these
      criteria. These putative stem cells are distinguished from other basal cells by
      their characteristic expression of high levels of the adhesion molecule alpha6, a
      member of the integrin family (alpha6bri), and low levels of a proliferation
      associated cell surface marker recognized by recently described mAb 10G7
      (10G7(dim)). We conclude that cells with the phenotype alpha6bri10G7(dim)
      represent the epidermal stem cell population based on the demonstration that
      these cells (i) exhibit the greatest regenerative capacity of any basal cells,
      (ii) represent a minor subpopulation (approximately 10%) of immature epidermal
      cells, which (iii) are quiescent at the time of isolation from the epidermis, as
      determined by cell cycle analysis.

PMID- 9520466
TI  - Engraftment and migration of human bone marrow stromal cells implanted in the
      brains of albino rats--similarities to astrocyte grafts.
AB  - Neurotransplantation has been used to explore the development of the central
      nervous system and for repair of diseased tissue in conditions such as
      Parkinson's disease. Here, we examine the effects of direct injection into rat
      brain of human marrow stromal cells (MSCs), a subset of cells from bone marrow
      that include stem-like precursors for nonhematopoietic tissues. Human MSCs
      isolated by their adherence to plastic were infused into the corpus striatum.
      Five to 72 days later, brain sections were examined for the presence of the donor
      cells. About 20% of the infused cells had engrafted. There was no evidence of an
      inflammatory response or rejection. The cells had migrated from the injection
      site along known pathways for migration of neural stem cells to successive layers
      of the brain. After infusion into the brain, the human MSCs lost their
      immunoreactivity to antibodies for collagen I. Initially, the human cells
      continued to stain with antibodies to fibronectin but the region of staining with
      fibronectin was significantly decreased at 30 and 72 days. The results suggest
      that MSCs may be useful vehicles for autotransplantation in both cell and gene
      therapy for a variety of diseases of the central nervous system.

PMID- 9520467
TI  - Budesonide epimer R or dexamethasone selectively inhibit platelet-activating
      factor-induced or interleukin 1beta-induced DNA binding activity of cis-acting
      transcription factors and cyclooxygenase-2 gene expression in human epidermal
      keratinocytes.
AB  - To further understand the molecular mechanism of glucocorticoid action on gene
      expression, DNA-binding activities of the cis-acting transcription factors
      activator protein 1 (AP1), AP2, Egr1 (zif268), NF-kappaB, the signal transducers
      and activators of transcription proteins gamma interferon activation site (GAS),
      Sis-inducible element, and the TATA binding protein transcription factor II D
      (TFIID) were examined in human epidermal keratinocytes. The cytokine interleukin
      1beta (IL-1beta) and platelet-activating factor (PAF), both potent mediators of
      inflammation, were used as triggers for gene expression. Budesonide epimer R
      (BUDeR) and dexamethasone (DEX) were studied as potential antagonists. BUDeR or
      DEX before IL-1beta- or PAF-mediated gene induction elicited strong inhibition of
      AP1-, GAS-, and in particular NF-kappaB-DNA binding (P < 0.001, ANOVA). Only
      small effects were noted on AP2, Egr1 (zif268), and Sis-inducible element-DNA
      binding (P > 0.05). No significant effect was noted on the basal transcription
      factor TFIID recognition of TATA-containing core promoter sequences (P > 0.68).
      To test the hypothesis that changing cis-acting transcription factor binding
      activity may be involved in inflammatory-response related gene transcription, RNA
      message abundance for human cyclooxygenase (COX)-1 and -2 (E.C.1.14.99.1) was
      assessed in parallel by using reverse transcription-PCR. Although the COX-1 gene
      was found to be expressed at constitutively low levels, the TATA-containing COX-2
      gene, which contains AP1-like, GAS, and NF-kappaB DNA-binding sites in its
      immediate promoter, was found to be strongly induced by IL-1beta or PAF (P <
      0.001). BUDeR and DEX both suppressed COX-2 RNA message generation; however, no
      correlation was associated with TFIID-DNA binding. These results suggest that on
      stimulation by mediators of inflammation, although the basal transcription
      machinery remains intact, modulation of cis-activating transcription factor AP1,
      GAS, and NF-kappaB-DNA binding by the glucocorticoids BUDeR and DEX play
      important regulatory roles in the extent of specific promoter activation and
      hence the expression of key genes involved in the inflammatory response.

PMID- 9520468
TI  - Directed changes in the number of double-stranded RNA genomic segments in
      bacteriophage phi6.
AB  - Bacteriophage Phi6 has a genome of three segments of double-stranded RNA. The
      segments are designated S, M, and L. Each segment has a unique packaging site,
      pac, near the 5' end of the plus strand. The plus strands of the segments are
      normally packaged in the order S, M, L. Chimeras of segment M and S in which
      segment M is at the 5' end of the plus strand can be stably incorporated into the
      virion; however, an independent segment S must be included along with normal
      segment L, even if it contains no active genes. A chimera of segment M and S in
      which segment S is at the 5' end of the plus strand can be stably incorporated
      into the virion along with normal segment L to form a two-segment genome. A
      chimera of segments S, M, and L in which the packaging sequence is that of S can
      also form a stable nonsegmented genome. These findings are consistent with a
      model that we have proposed for the packaging of the Phi6 genome.

PMID- 9520469
TI  - Epithelial attachment alters the outcome of Helicobacter pylori infection.
AB  - Genetically defined in vivo models are needed to assess the importance of target
      cell attachment in bacterial pathogenesis. Gastric colonization by Helicobacter
      pylori in human populations is common and persistent, and has various outcomes
      including peptic ulcers and cancer. The impact of attachment on the course of
      infection was examined in transgenic mice expressing a human receptor for H.
      pylori in their gastric epithelium. Persistent infection by a clinical isolate
      occurred at comparable microbial densities in transgenic and nontransgenic
      littermates. However, microbial attachment in transgenic mice resulted in
      production of autoantibodies to Lewisx carbohydrate epitopes shared by bacteria
      and acid-secreting parietal cells, chronic gastritis, and parietal cell loss.
      This model should help identify bacterial and host genes that produce attachment
      related pathology.

PMID- 9520470
TI  - Herpes simplex virus 1 induces and blocks apoptosis at multiple steps during
      infection and protects cells from exogenous inducers in a cell-type-dependent
      manner.
AB  - Several publications have attested to the ability of herpes simplex viruses to
      protect cells against apoptosis. We investigated the ability of the virus to
      protect cells in continuous cultivation from apoptosis induced by the virus
      itself, and by other known inducers such as exposure to the tumor necrosis factor
      alpha (TNFalpha), antibody to Fas, C2-ceramide, osmotic shock (sorbitol), and
      thermal shock. The salient features of the results were that the virus was able
      to protect cells against apoptosis by all of the agents tested, and that
      apoptosis induced by the virus was a very early event that did not require de
      novo expression of viral genes. However, these events were cell-type specific.
      Thus: (i) The cell lines tested exhibited fragmented chromosomal DNA following
      infection with a virus lacking functional alpha4 and US3 genes encoding the major
      regulatory protein and a viral protein kinase, respectively, but not by wild-type
      virus. (ii) Wild-type virus protected subconfluent SK-N-SH but not HeLa cells
      against induction of apoptosis by anti-Fas antibody, TNFalpha, C2-ceramide, and
      thermal shock. Confluent SK-N-SH cells were not protected from osmotic shock
      induced apoptosis by wild-type infection. (iii) Wild-type virus protected SK-N-SH
      but not HeLa cells against induction of apoptosis by sorbitol, anti-Fas antibody,
      or TNFalpha and C2-ceramide. (iv) Mutant HSV-1(HFEM)tsB7 at the nonpermissive
      temperature infects cells but the DNA is not released from capsids, and therefore
      viral gene expression is restricted to the function of viral proteins introduced
      into the cell along with the capsid containing the viral DNA. HSV-1(HFEM)tsB7
      induced apoptosis in Vero cells but not in SK-N-SH cells infected and maintained
      at 39.5 degrees C. (v) Tests of two caspase inhibitors showed that they blocked
      apoptosis induced by C2-ceramide and sorbitol, but were not able to block
      apoptosis induced by the virus lacking functional alpha4 and US3 genes. We
      conclude that HSV-1 triggers apoptosis at multiple metabolic checkpoints and in
      turn has evolved mechanisms to block apoptosis at each point and that some of the
      pathways of induction are shared with exogenous inducers tested in this study
      whereas others are not.

PMID- 9520471
TI  - Cytomegalovirus remains latent in a common precursor of dendritic and myeloid
      cells.
AB  - Hematopoietic cells and their progenitors play important roles in human
      cytomegalovirus latency and reactivation. Latent infection has been evaluated in
      defined populations of myeloid-lineage-committed progenitor cells coexpressing
      CD33 and CD15 or CD33 and CD14 along with the dendritic cell markers CD1a and
      CD10. These CD33+ cell populations were found to support latency and expression
      of viral latency-associated transcripts and to undergo reactivation of productive
      viral replication when differentiated in the presence of human fibroblasts.
      Reactivation was also observed when myeloid cells were carried in the presence of
      fibroblast-conditioned medium or medium supplemented with certain cytokines
      (interferon gamma, tumor necrosis factor alpha, interleukin 4, or granulocyte
      macrophage colony-simulating factor), suggesting that cell differentiation
      pathways act as determinants of reactivation. More primitive CD34+ hematopoietic
      cells were also found to be susceptible to viral infection and latency was
      maintained as these cells differentiated into CD33+-lineage-committed
      populations. Between 0.01% and 0.001% of CD33+ CD14+ or CD33+ CD15+ bone marrow
      mononuclear cells isolated from naturally infected individuals were found to
      express latent transcripts. Thus, cytomegalovirus is carried within a small
      percentage of myeloid and dendritic cell progenitors in the healthy seropositive
      host. Virus reactivation may be triggered by factors associated with the
      inflammatory response.

PMID- 9520472
TI  - "Black holes" and bacterial pathogenicity: a large genomic deletion that enhances
      the virulence of Shigella spp. and enteroinvasive Escherichia coli.
AB  - Plasmids, bacteriophages, and pathogenicity islands are genomic additions that
      contribute to the evolution of bacterial pathogens. For example, Shigella spp.,
      the causative agents of bacillary dysentery, differ from the closely related
      commensal Escherichia coli in the presence of a plasmid in Shigella that encodes
      virulence functions. However, pathogenic bacteria also may lack properties that
      are characteristic of nonpathogens. Lysine decarboxylase (LDC) activity is
      present in approximately 90% of E. coli strains but is uniformly absent in
      Shigella strains. When the gene for LDC, cadA, was introduced into Shigella
      flexneri 2a, virulence became attenuated, and enterotoxin activity was inhibited
      greatly. The enterotoxin inhibitor was identified as cadaverine, a product of the
      reaction catalyzed by LDC. Comparison of the S. flexneri 2a and laboratory E.
      coli K-12 genomes in the region of cadA revealed a large deletion in Shigella.
      Representative strains of Shigella spp. and enteroinvasive E. coli displayed
      similar deletions of cadA. Our results suggest that, as Shigella spp. evolved
      from E. coli to become pathogens, they not only acquired virulence genes on a
      plasmid but also shed genes via deletions. The formation of these "black holes,"
      deletions of genes that are detrimental to a pathogenic lifestyle, provides an
      evolutionary pathway that enables a pathogen to enhance virulence. Furthermore,
      the demonstration that cadaverine can inhibit enterotoxin activity may lead to
      more general models about toxin activity or entry into cells and suggests an
      avenue for antitoxin therapy. Thus, understanding the role of black holes in
      pathogen evolution may yield clues to new treatments of infectious diseases.

PMID- 9520473
TI  - Virulence of antibiotic-resistant Salmonella typhimurium.
AB  - We show that most Salmonella typhimurium mutants resistant to streptomycin,
      rifampicin, and nalidixic acid are avirulent in mice. Of seven resistant mutants
      examined, six were avirulent and one was similar to the wild type in competition
      experiments in mice. The avirulent-resistant mutants rapidly accumulated various
      types of compensatory mutations that restored virulence without concomitant loss
      of resistance. Such second-site compensatory mutations were more common then
      reversion to the sensitive wild type. We infer from these results that a
      reduction in the use of antibiotics might not result in the disappearance of the
      resistant bacteria already present in human and environmental reservoirs. Thus,
      second-site compensatory mutations could increase the fitness of resistant
      bacteria and allow them to persist and compete successfully with sensitive
      strains even in an antibiotic-free environment.

PMID- 9520474
TI  - Recombinant viruses expressing a human malaria antigen can elicit potentially
      protective immune CD8+ responses in mice.
AB  - Extensive studies on protective immunity to rodent malaria provided the basis for
      the current experiments in which mice were immunized with recombinant (re)
      influenza and vaccinia viruses expressing selected sequences of the
      circumsporozoite (CS) protein of the human malaria parasite Plasmodium
      falciparum. Mice of different H-2 haplotypes immunized with re influenza viruses
      expressing the immunodominant B cell epitope of this CS protein produced high
      titers of antibodies to the parasite. A cytotoxic T lymphocyte epitope of the CS
      protein of P. falciparum, PF3, recognized by CD8+ T cells of H-2(k) mice, was
      expressed in a re vaccinia virus (VacPf) and a re influenza virus (FluPf).
      Immunization of mice with either FluPf or VacPf elicited a modest CS-specific
      CD8+ T cell response detected by interferon gamma secretion of individual immune
      cells. Priming of mice with FluPf, followed by a booster with VacPf, resulted in
      a striking enhancement of this T cell response. The reverse protocol, i.e.,
      priming with VacPf followed by a booster with FluPf, failed to enhance the
      primary response. VacPf also greatly enhanced the primary response of mice
      injected with P. falciparum sporozoites or with a lipopeptide containing PF3. A
      booster with FluPf also amplified the response of lipopeptide- or sporozoite
      primed mice but less than a VacPf booster did. Although mice are not susceptible
      to infection by P. falciparum sporozoites, we demonstrated that administration of
      two distinct immunogens expressing PF3 elicited activated, extravasating CS
      specific T cells that protected against an intracerebral VacPf challenge.

PMID- 9520475
TI  - staggerer phenotype in retinoid-related orphan receptor alpha-deficient mice.
AB  - Retinoid-related orphan receptor alpha (RORalpha) is a member of the nuclear
      receptor superfamily. To study its physiological role we generated null-mutant
      mice by targeted insertion of a lacZ reporter gene encoding the enzyme beta
      galactosidase. In heterozygous RORalpha+/- mice we found beta-galactosidase
      activity, indicative of RORalpha protein expression, confined to the central
      nervous system, skin and testis. In the central nervous system, the RORalpha gene
      is expressed in cerebellar Purkinje cells, the thalamus, the suprachiasmatic
      nuclei, and retinal ganglion cells. In skin, RORalpha is strongly expressed in
      the hair follicle, the epidermis, and the sebaceous gland. Finally, the
      peritubular cells of the testis and the epithelial cells of the epididymis also
      strongly express RORalpha. Recently, it was reported that the ataxic mouse mutant
      staggerer (sg/sg) is caused by a deletion in the RORalpha gene. The analysis of
      the cerebellar and the behavioral phenotype of homozygous RORalpha-/- mice proves
      identity to sg/sg mice. Although the absence of RORalpha causes dramatic
      developmental effects in the cerebellum, it has no apparent morphological effect
      on thalamus, hypothalamus, and retina. Similarly, testis and skin of RORalpha-/-
      mice display a normal phenotype. However, the pelage hair of both sg/sg and
      RORalpha-/- is significantly less dense and when shaved shows reluctance to
      regrow.

PMID- 9520476
TI  - Neuronal polarity: essential role of protein-lipid complexes in axonal sorting.
AB  - The viral glycoprotein hemagglutinin (HA) and the endogenous
      glycosylphosphatidylinositol-anchored protein Thy-1 are efficiently targeted to
      the axonal surface of fully polarized hippocampal neurons in culture. Here we
      have shown that in these cells HA and Thy-1 interact with sphingolipid
      cholesterol rafts and are included in detergent-insoluble glycolipid-enriched
      complexes. Axonal HA and Thy-1, but not two dendritic membrane proteins, resisted
      extraction to detergents at 4 degrees C. Both HA and Thy-1 became detergent
      soluble in neurons with reduced levels of cholesterol or sphingolipids.
      Missorting of the axonal Thy-1 but not of a dendritic membrane protein occurred
      in sphingolipid-deprived cells. These results indicate that neurons sort a subset
      of axolemmal proteins by a mechanism that requires the formation of protein-lipid
      rafts. The involvement of rafts in axonal membrane sorting may explain the
      neurological deficits observed in patients with certain types of Niemann-Pick
      disease.

PMID- 9520477
TI  - Proteolytic processing of the Aplysia egg-laying hormone prohormone.
AB  - By using matrix-assisted laser desorption/ionization time-of-flight MS,
      individual peptidergic neurons from Aplysia are assayed. A semiquantitative
      method is developed for comparing single-cell profiles by using spectral
      normalization, and peptides are localized to specific cells by mass spectrometric
      cell mapping. In addition to all previously identified products of the egg-laying
      hormone (ELH) gene, other peptides are formed from proteolytic hydrolysis of Leu
      Leu residues within ELH and acidic peptide (AP). AP exhibits further processing
      to yield AP1-20 and AP9-27. These peptides appear to be colocalized in vesicles
      with ELH, transported to specific neuronal targets, and released in a Ca2+
      dependent manner. A differential peptide distribution is observed at a specific
      target cell, and a low-frequency variation of AP, [Thr21]AP, is detected in a
      single animal.

PMID- 9520478
TI  - Prolonged delivery of brain-derived neurotrophic factor by adenovirus-infected
      Muller cells temporarily rescues injured retinal ganglion cells.
AB  - In this study, we demonstrate that: (i) injection of an adenovirus (Ad) vector
      containing the brain-derived neurotrophic factor (BDNF) gene (Ad.BDNF) into the
      vitreous chamber of adult rats results in selective transgene expression by
      Muller cells; (ii) in vitro, Muller cells infected with Ad.BDNF secrete BDNF that
      enhances neuronal survival; (iii) in vivo, Ad-mediated expression of functional
      BDNF by Muller cells, temporarily extends the survival of axotomized retinal
      ganglion cells (RGCs); 16 days after axotomy, injured retinas treated with
      Ad.BDNF showed a 4.5-fold increase in surviving RGCs compared with control
      retinas; (iv) the transient expression of the BDNF transgene, which lasted
      approximately 10 days, can be prolonged with immunosuppression for at least 30
      days, and such Ad-mediated BDNF remains biologically active, (v) persistent
      expression of BDNF by infected Muller cells does not further enhance the survival
      of injured RGCs, indicating that the effect of this neurotrophin on RGC survival
      is limited by changes induced by the lesion within 10-16 days after optic nerve
      transection rather than the availability of BDNF. Thus, Ad-transduced Muller
      cells are a novel pathway for sustained delivery of BDNF to acutely-injured RGCs.
      Because these cells span the entire thickness of the retina, Ad-mediated gene
      delivery to Muller cells may also be useful to influence photoreceptors and other
      retinal neurons.

PMID- 9520479
TI  - The small GTP-binding protein Cdc42 is required for nerve growth factor
      withdrawal-induced neuronal death.
AB  - An increase in the level of the c-Jun transcription factor and of its
      phosphorylation has previously been shown to be essential for nerve growth factor
      (NGF) withdrawal-induced apoptosis of rat sympathetic neurons (SCG). The Rho-like
      GTPases Cdc42 and Rac1 are involved in the regulation of a number of cellular
      processes, including activation of the c-Jun NH2-terminal kinase (JNK) pathway.
      Therefore, we have investigated the role of these GTPases in this process.
      Overexpression of activated Rac1 or Cdc42 in SCG neurons maintained in the
      presence of NGF induced apoptosis, whereas expression of dominant negative
      mutants of Cdc42 or Rac1 blocked apoptosis following NGF withdrawal. Cdc42
      activation produced an increase in the level of c-Jun and of its phosphorylation.
      Furthermore, Cdc42-induced death was prevented by coexpressing the c-Jun dominant
      negative FLAGDelta169. Thus, Cdc42 appears to function as an initiator of
      neuronal cell death by activating a transcriptional pathway regulated by c-Jun.

PMID- 9520480
TI  - Expression of monocarboxylate transporter mRNAs in mouse brain: support for a
      distinct role of lactate as an energy substrate for the neonatal vs. adult brain.
AB  - Under particular circumstances like lactation and fasting, the blood-borne
      monocarboxylates acetoacetate, beta-hydroxybutyrate, and lactate represent
      significant energy substrates for the brain. Their utilization is dependent on a
      transport system present on both endothelial cells forming the blood-brain
      barrier and on intraparenchymal brain cells. Recently, two monocarboxylate
      transporters, MCT1 and MCT2, have been cloned. We report here the
      characterization by Northern blot analysis and by in situ hybridization of the
      expression of MCT1 and MCT2 mRNAs in the mouse brain. In adults, both transporter
      mRNAs are highly expressed in the cortex, the hippocampus and the cerebellum.
      During development, a peak in the expression of both transporters occurs around
      postnatal day 15, declining rapidly by 30 days at levels observed in adults.
      Double-labeling experiments reveal that the expression of MCT1 mRNA in
      endothelial cells is highest at postnatal day 15 and is not detectable at adult
      stages. These results support the notion that monocarboxylates are important
      energy substrates for the brain at early postnatal stages and are consistent with
      the sharp decrease in blood-borne monocarboxylate utilization after weaning. In
      addition, the observation of a sustained intraparenchymal expression of
      monocarboxylate transporter mRNAs in adults, in face of the seemingly complete
      disappearance of their expression on endothelial cells, reinforces the view that
      an intercellular exchange of lactate occurs within the adult brain.

PMID- 9520481
TI  - A tripotential glial precursor cell is present in the developing spinal cord.
AB  - We have isolated a tripotential glial precursor cell population from spinal cords
      of E13.5 rats. In vitro, these A2B5+E-NCAM- glial-restricted precursor (GRP)
      cells can undergo extensive self-renewal, and can differentiate into
      oligodendrocytes and two distinct astrocyte populations, but do not differentiate
      into neurons. The differentiation potential of GRP cells is retained through at
      least three cycles of expansion and recloning. Unlike oligodendrocyte-type 2
      astrocyte progenitor cells, freshly isolated GRP cells do not respond to platelet
      derived growth factor as a mitogen or survival factor, nor do GRP cells
      differentiate into oligodendrocytes--or even survive--when plated in mitogen-free
      chemically defined medium. Exposure to fetal calf serum induces GRP cells to
      differentiate into A2B5- fibroblast-like astrocytes, whereas growth in the
      presence of basic fibroblast growth factor and ciliary neurotrophic factor
      induces the generation of A2B5+ process-bearing astrocytes. The early appearance
      of GRP cells during spinal cord development suggests that they may represent the
      earliest GRP cell population.

PMID- 9520482
TI  - The distribution of oriented contours in the real world.
AB  - In both humans and experimental animals, the ability to perceive contours that
      are vertically or horizontally oriented is superior to the perception of oblique
      angles. There is, however, no consensus about the developmental origins or
      functional basis of this phenomenon. Here, we report the analysis of a large
      library of digitized scenes using image processing with orientation-sensitive
      filters. Our results show a prevalence of vertical and horizontal orientations in
      indoor, outdoor, and even entirely natural settings. Because visual experience is
      known to influence the development of visual cortical circuitry, we suggest that
      this real world anisotropy is related to the enhanced ability of humans and other
      animals to process contours in the cardinal axes, perhaps by stimulating the
      development of a greater amount of visual circuitry devoted to processing
      vertical and horizontal contours.

PMID- 9520483
TI  - Mechanism of nicotinic acetylcholine receptor cluster formation by rapsyn.
AB  - Rapsyn, a peripheral membrane protein of skeletal muscle, clusters nicotinic
      acetylcholine receptors (nAChRs) at high density in the postsynaptic membrane.
      The mechanism of nAChR clustering by rapsyn was analyzed by expressing nAChRs in
      HEK293T cells with various fragments of mouse rapsyn fused to green fluorescent
      protein. Membrane targeting of rapsyn is conferred solely by its acylated N
      terminus, as the myristoylated N-terminal 15 amino acids of rapsyn are sufficient
      to target green fluorescent protein to the plasma membrane. However, neither N
      terminal myristoylation nor the conserved N-terminal amino acid sequence is
      essential. Membrane targeting, self-association, and nAChR clustering are
      preserved when the first 10 amino acids of rapsyn were replaced by those of src,
      which also contains a consensus sequence for N-myristoylation, or by those of
      GAP43, which contains a palmitoylation sequence. Rapsyn1-90, containing two
      tetratrichopeptide repeats is sufficient for self-association. Rapsyn1-360,
      lacking the cysteine rich domain, clusters nAChRs, while rapsyn1-287, containing
      seven tetratrichopeptide repeats, does not cluster nAChRs. We identified
      rapsyn298-331 as a potential coiled-coil domain, and established that mutations
      disrupting coiled-coil propensity prevent nAChR clustering. Thus the structural
      domains of rapsyn necessary for membrane targeting, self-association, and nAChR
      clustering are distinct, with nAChR-rapsyn interaction mediated by a previously
      unrecognized coiled-coil motif.

PMID- 9520485
TI  - Cloning and functional expression of alternative spliced variants of the rho1
      gamma-aminobutyrate receptor.
AB  - The rho1 gamma-aminobutyrate receptor (GABArho1) is expressed predominantly in
      the retina and forms homomeric GABA-gated Cl- channels that are clearly different
      from the multisubunit GABAA receptors. In contrast to these, GABArho1 receptors
      desensitize very little and are not blocked by bicuculline. In addition to
      GABArho1, two new variants were identified in human retina cDNA libraries.
      Cloning and sequence analysis showed that both variants contain large deletions
      in the putative extracellular domain of the receptor. These deletions extend from
      a common 5' site to different 3' sites. The cDNA with the largest deletion, named
      GABArho1Delta450, contains a complete ORF identical to that of GABArho1 but
      missing 450 nt. This cDNA encodes a protein of 323 aa, identical to the GABArho1,
      but has a deletion of 150 aa in the amino-terminal extracellular domain.
      GABArho1Delta450 mRNA injected into Xenopus oocytes did not produce functional
      GABA receptors. The second GABArho1 variant (GABArho1Delta51) contains a 51-nt
      deletion. In Xenopus oocytes, GABArho1Delta51 led to the expression of GABA
      receptors that had the essential GABArho1 characteristics of low desensitization
      and bicuculline resistance. Therefore, alternative splicing increases the coding
      potential of this gene family expressed in the human retina, but the functional
      diversity created by the alternative spliced forms is still not understood.

PMID- 9520484
TI  - Nurr1 is essential for the induction of the dopaminergic phenotype and the
      survival of ventral mesencephalic late dopaminergic precursor neurons.
AB  - Nurr1 is a member of the nuclear receptor superfamily of transcription factors
      that is expressed predominantly in the central nervous system, including
      developing and mature dopaminergic neurons. Recent studies have demonstrated that
      Nurr1 is essential for the induction of phenotypic markers of ventral mid-brain
      dopaminergic neurons whose generation is specified by the floor plate-derived
      morphogenic signal sonic hedgehog (SHH), but the precise role of Nurr1 in this
      differentiative pathway has not been established. To provide further insights
      into the role of Nurr1 in the final differentiation pathway, we have examined the
      fate of dopamine cell precursors in Nurr1 null mutant mice. Here we demonstrate
      that Nurr1 functions at the later stages of dopamine cell development to drive
      differentiation of ventral mesencephalic late dopaminergic precursor neurons. In
      the absence of Nurr1, neuroepithelial cells that give rise to dopaminergic
      neurons adopt a normal ventral localization and neuronal phenotype characterized
      by expression of the homeodomain transcription factor and mesencephalic marker,
      Ptx-3, at embryonic day 11.5. However, these late precursors fail to induce a
      dopaminergic phenotype, indicating that Nurr1 is essential for specifying
      commitment of mesencephalic precursors to the full dopaminergic phenotype.
      Further, as development progresses, these mid-brain dopamine precursor cells
      degenerate in the absence of Nurr1, resulting in loss of Ptx-3 expression and a
      concomitant increase in apoptosis of ventral midbrain neurons in newborn null
      mutant mice. Taken together, these data indicate that Nurr1 is essential for both
      survival and final differentiation of ventral mesencephalic late dopaminergic
      precursor neurons into a complete dopaminergic phenotype.

PMID- 9520486
TI  - Developmental patterns in the cytoarchitecture of the human cerebral cortex from
      birth to 6 years examined by correspondence analysis.
AB  - This paper uses correspondence analysis to examine the developmental patterns in
      the cytoarchitecture of the human cerebral cortex from birth to 72 months. The
      study is based on data collected by the late J. L. Conel, which consist of over 4
      million individual measurements of six microscopic neuroanatomic features for
      each of six cortical layers in 46 cytoarchitecturally distinct regions. We
      analyze 1,727 profiles of development over eight age-points (term birth, 1, 3, 6,
      15, 24, 48, and 72 postnatal months) resulting from the combinations of
      neuroanatomic feature, cortical layer, and brain cytoarchitectural region in the
      Conel data. The profiles for any given combination of feature and layer are found
      to be remarkably similar in all regions of the brain, and therefore the
      developmental patterns of different cytoarchitectural regions are not
      distinguishable from one another. Developmental change is most rapid at the
      earlier stages; of the total change in profile patterns observed, more than one
      third occurs between birth and 6 months, about one-third occurs between 6 and 15
      months, and less than one-third occurs between 15 and 72 months. The majority of
      the variance in developmental profiles is accounted for by the six microscopic,
      neuroanatomic features. Correspondence analysis shows that Conel's data are
      highly consistent and reliable.

PMID- 9520487
TI  - Profound neuronal plasticity in response to inactivation of the dopamine
      transporter.
AB  - The dopamine transporter (DAT) plays an important role in calibrating the
      duration and intensity of dopamine neurotransmission in the central nervous
      system. We have used a strain of mice in which the gene for the DAT has been
      genetically deleted to identify the DAT's homeostatic role. We find that removal
      of the DAT dramatically prolongs the lifetime (300 times) of extracellular
      dopamine. Within the time frame of neurotransmission, no other processes besides
      diffusion can compensate for the lack of the DAT, and the absence of the DAT
      produces extensive adaptive changes to control dopamine neurotransmission.
      Despite the absence of a clearance mechanism, dopamine extracellular levels were
      only 5 times greater than control animals due to a 95% reduction in content and a
      75% reduction in release. Paradoxically, dopamine synthesis rates are doubled
      despite a decrease of 90% in the levels of tyrosine hydroxylase and degradation
      is markedly enhanced. Thus, the DAT not only controls the duration of
      extracellular dopamine signals but also plays a critical role in regulating
      presynaptic dopamine homeostasis. It is interesting to consider that the switch
      to a dopamine-deficient, but functionally hyperactive, mode of neurotransmission
      observed in mice lacking the DAT may represent an extreme example of neuronal
      plasticity resulting from long-term psychostimulant abuse.

PMID- 9520488
TI  - Decay of prepulse facilitation of N type calcium channels during G protein
      inhibition is consistent with binding of a single Gbeta subunit.
AB  - We have examined the modulation of cloned and stably expressed rat brain N type
      calcium channels (alpha1B + beta1b + alpha2delta subunits) by exogenously applied
      purified G protein betagamma subunits. In the absence of Gbetagamma, barium
      currents through N type channels are unaffected by application of strong
      depolarizing prepulses. In contrast, inclusion of purified Gbetagamma in the
      patch pipette results in N type currents that initially facilitated upon
      application of positive prepulses followed by rapid reinhibition. Examination of
      the kinetics of Gbetagamma-dependent reinhibition showed that as the duration
      between the test pulse and the prepulse was increased, the degree of facilitation
      was attenuated in a monoexponential fashion. The time constant tau for the
      recovery from facilitation was sensitive to exogenous Gbetagamma, so that the
      inverse of tau linearly depended on the Gbetagamma concentration. Overall, the
      data are consistent with a model whereby a single Gbetagamma molecule dissociates
      from the channel during the prepulse, and that reassociation of Gbetagamma with
      the channel after the prepulse occurs as a bimolecular reaction.

PMID- 9520489
TI  - Calcimimetics with potent and selective activity on the parathyroid calcium
      receptor.
AB  - Parathyroid hormone (PTH) secretion is regulated by a cell surface Ca2+ receptor
      that detects small changes in the level of plasma Ca2+. Because this G protein
      coupled receptor conceivably provides a distinct molecular target for drugs
      useful in treating bone and mineral-related disorders, we sought to design small
      organic molecules that act on the Ca2+ receptor. We discovered that certain
      phenylalkylamine compounds, typified by NPS R-568 and its deschloro derivative
      NPS R-467, increased the concentration of cytoplasmic Ca2+ ([Ca2+]i) in bovine
      parathyroid cells and inhibited PTH secretion at nanomolar concentrations. These
      effects were stereoselective and the R enantiomers were 10- to 100-fold more
      potent than the S enantiomers. NPS R-568 potentiated the effects of extracellular
      Ca2+ on [Ca2+]i and PTH secretion but was without effect in the absence of
      extracellular Ca2+. Both compounds shifted the concentration-response curves for
      extracellular Ca2+ to the left. Presumably, these compounds act as positive
      allosteric modulators to increase the sensitivity of the Ca2+ receptor to
      activation by extracellular Ca2+. Both NPS R-467 and NPS R-568 increased [Ca2+]i
      in HEK 293 cells expressing the human parathyroid Ca2+ receptor but were without
      effect in wild-type HEK 293 cells. Neither compound affected the cytoplasmic Ca2+
      responses elicited by several other G protein-coupled receptors in HEK 293 cells
      or in bovine parathyroid cells. Significantly, these compounds did not affect
      responses elicited by the homologous metabotropic glutamate receptors, mGluR1a,
      mGluR2, or mGluR8. These compounds therefore act selectively on the Ca2+
      receptor. Compounds that mimic or potentiate the effects of extracellular Ca2+ at
      the Ca2+ receptor are termed calcimimetics. The discovery of calcimimetic
      compounds with potent and selective activity enables a pharmacological approach
      to regulating plasma levels of PTH. Calcimimetic compounds could conceivably
      provide a specific medical therapy for primary hyperparathyroidism.

PMID- 9520491
TI  - Seminal fluid regulation of female sexual attractiveness in Drosophila
      melanogaster.
AB  - Finding a willing and suitable mate is critical for sexual reproduction. Visual,
      auditory, and chemical cues aid in locating and/or attracting partners. After
      mating, females from many insect species become less attractive. This is caused
      by changes in the quantity and/or quality of pheromones synthesized by the female
      and to changes in the female's behavior. For example, female insects may stop
      releasing pheromones, assume a mate refusal posture, or move less in response to
      males. Many postmating changes in female insects are triggered by seminal fluid
      proteins from the male's accessory gland proteins (Acps) and by sperm. To
      determine the role of seminal fluid components in mediating changes in
      attractiveness, we measured the attractiveness of Drosophila melanogaster females
      that had been mated to genetically altered males that lack sperm and/or Acps. We
      found that the drop in female attractiveness occurs in two phases. A short-term
      drop in attractiveness is triggered independent of the receipt of sperm and Acps.
      Maintenance of lowered attractiveness is dependent upon sperm.

PMID- 9520490
TI  - The yeast CLC chloride channel functions in cation homeostasis.
AB  - A defect in the yeast GEF1 gene, a CLC chloride channel homolog leads to an iron
      requirement and cation sensitivity. The iron requirement is due to a failure to
      load Cu2+ onto a component of the iron uptake system, Fet3. This process, which
      requires both Gef1 and the Menkes disease Cu2+-ATPase yeast homolog Ccc2, occurs
      in late- or post-Golgi vesicles, where Gef1 and Ccc2 are localized. The defects
      of gef1 mutants can be suppressed by the introduction of Torpedo marmorata CLC-0
      or Arabidopsis thaliana CLC-c and -d chloride channel genes. The functions of
      Gef1 in cation homeostasis provide clues to the understanding of diseases caused
      by chloride channel mutations in humans and cation toxicity in plants.

PMID- 9520492
TI  - Activity patterns of neurosecretory cells releasing pheromonotropic neuropeptides
      in the moth Bombyx mori.
AB  - Short- and long-term firing patterns of neurosecretory cells releasing
      pheromonotropic neuropeptides in the silkworm moth Bombyx mori were examined. The
      cells showed three types of rhythmic changes in firing activity. Bursting
      activities with an interval of several seconds were synchronized with rhythmic
      abdominal motions for calling behavior. A slow fluctuation in firing activity
      over a period of several minutes depended on cyclic alternations of the flow of
      hemolymph. The electrical activity displayed a diel rhythm that related to
      light/dark cycles of the environment and sex pheromone titers in the pheromone
      gland. In addition to a transient inhibition of firing caused by a tactile or
      light stimulus, a long-term permanent inhibition was induced by mating with a
      fertile male. Thus, the insect neurosecretory system is highly coordinated with
      physiology and behavior in Bombyx mori and is influenced by external stimuli.

PMID- 9520495
TI  - The Black-Scholes pricing formula in the quantum context.
AB  - A natural explanation for extreme irregularities in the evolution of prices in
      financial markets is provided by quantum effects. The lack of simultaneous
      observability of relevant variables and the interference of attempted observation
      with the values of these variables represent such effects. These characteristics
      have been noted by traders and economists and appear intrinsic to market
      dynamics. This explanation is explored here in terms of a corresponding
      generalization of the Wiener process and its role in the Black-Scholes-Merton
      theory. The differentiability of the Wiener process as a sesquilinear form on a
      dense domain in the Hilbert space of square-integrable functions over Wiener
      space is shown and is extended to the quantum context. This provides a basis for
      a corresponding generalization of the Ito theory of stochastic integration. An
      extension of the Black-Scholes option pricing formula to the quantum context is
      deduced.

PMID- 9520493
TI  - Diet-induced changes in uncoupling proteins in obesity-prone and obesity
      resistant strains of mice.
AB  - Uncoupling protein 2 (UCP2) maps to a region on distal mouse chromosome 7 that
      has been linked to the phenotypes of obesity and type II diabetes. We recently
      reported that UCP2 expression is increased by high fat feeding in adipose tissue
      of the A/J strain of mice, which is resistant to the development of dietary
      obesity. More recently, a third UCP (UCP3) was identified, which is expressed
      largely in skeletal muscle and brown adipose tissue. The UCP2 and UCP3 genes are
      located adjacent to one another on mouse chromosome 7. Thus, the roles of these
      UCPs in both metabolic efficiency and the linkage to obesity and diabetes
      syndromes is unclear. For this reason, we examined the expression of UCP2 and
      UCP3 in white adipose tissue and interscapular brown adipose tissue and in
      gastrocnemius/soleus muscle preparations from the obesity-resistant A/J and
      C57BL/KsJ (KsJ) strains and the obesity-prone C57BL/6J (B6) mouse strain. In both
      KsJ and A/J mice, UCP2 expression in white fat was increased approximately 2-fold
      in response to 2 weeks of a high fat diet, but there was no effect of diet on
      UCP2 levels in B6 mice. In skeletal muscle and in brown fat, neither UCP2 nor
      UCP3 expression was affected by diet in A/J, B6, or KsJ mice. However, in brown
      fat, we observed a 2-3-fold increase in the expression of UCP1 in response to
      dietary fat challenge, which may be related to diet-induced elevations in plasma
      leptin levels. Together, these results indicate that the consumption of a high
      fat diet selectively regulates UCP2 expression in white fat and UCP1 expression
      in brown fat and that resistance to obesity is correlated with this early,
      selective induction of UCP1 and UCP2 and is not associated with changes in
      expression of UCP3.

PMID- 9520494
TI  - Stress facilitates classical conditioning in males, but impairs classical
      conditioning in females through activational effects of ovarian hormones.
AB  - Exposure to restraint and brief intermittent tailshocks facilitates associative
      learning of the classical conditioned eyeblink response in male rats. Based on
      evidence of sex differences in learning and responses to stressful events, we
      investigated sexually dimorphic effects of a stressor of restraint and
      intermittent tailshock on classical eyeblink conditioning 24 h after stressor
      cessation. Our results indicate that exposure to the acute stressor had
      diametrically opposed effects on the rate of acquisition of the conditioned
      response in male vs. female rats. Exposure to the stressor facilitated
      acquisition of the conditioned response in males, whereas exposure to the same
      stressful event dramatically impaired acquisition in females. We further
      demonstrate that the stress-induced impairment in female conditioning is
      dependent on the presence of ovarian hormones. Conditioning of stressed sham
      ovariectomized females was significantly impaired relative to the unstressed
      controls, whereas conditioning in stressed ovariectomized females was not
      impaired. We present additional evidence that estrogen mediates the stress
      induced impairment in female acquisition. Females administered sesame oil vehicle
      and then stressed were significantly impaired relative to their unstressed
      controls, whereas females administered the estrogen antagonist tamoxifen prior to
      stress were not impaired. In summary, these results indicate that exposure to the
      same aversive event can induce opposite behavioral responses in males vs.
      females. These effects underscore sex differences in associative learning and
      emotional responding, and implicate estrogen in the underlying neuronal
      mechanism.

PMID- 9520496
TI  - The Merck Gene Index browser: an extensible data integration system for gene
      finding, gene characterization and EST data mining.
AB  - MOTIVATION: To make effective use of the vast amounts of expressed sequence tag
      (EST) sequence data generated by the Merck-sponsored EST project and other
      similar efforts, sequences must be organized into gene classes, and scientists
      must be able to 'mine' the gene class data in the context of related genomic
      data. RESULTS: This paper presents the Merck Gene Index browser, an easily
      extensible, World Wide Web-based system for mining the Merck Gene Index (MGI) and
      related genomic data. The MGI is a non-redundant set of clones and sequences,
      each representing a distinct gene, constructed from all high-quality 3' EST
      sequences generated by the Merck-sponsored EST project. The MGI browser
      integrates data from a variety of sources and storage formats, both local and
      remote, using an eclectic integration strategy, including a federation of
      relational databases, a local data warehouse and simple hypertext links. Data
      currently integrated include: LENS cDNA clone and EST data, dbEST protein and non
      EST nucleic acid similarity data, WashU sequence chromatograms. Entrez sequence
      and Medline entries, and UniGene gene clusters. Flatfile sequence data are
      accessed using the Bioapps server, an internally developed client-server system
      that supports generic sequence analysis applications. Browser data are retrieved
      and formatted by means of the Bioinformatics Data Integration Toolkit (B-DIT), a
      new suite of Perl routines.

PMID- 9520497
TI  - Algorithms and software for support of gene identification experiments.
AB  - MOTIVATION: Gene annotation is the final goal of gene prediction algorithms.
      However, these algorithms frequently make mistakes and therefore the use of gene
      predictions for sequence annotation is hardly possible. As a result, biologists
      are forced to conduct time-consuming gene identification experiments by designing
      appropriate PCR primers to test cDNA libraries or applying RT-PCR, exon
      trapping/amplification, or other techniques. This process frequently amounts to
      'guessing' PCR primers on top of unreliable gene predictions and frequently leads
      to wasting of experimental efforts. RESULTS: The present paper proposes a simple
      and reliable algorithm for experimental gene identification which bypasses the
      unreliable gene prediction step. Studies of the performance of the algorithm on a
      sample of human genes indicate that an experimental protocol based on the
      algorithm's predictions achieves an accurate gene identification with relatively
      few PCR primers. Predictions of PCR primers may be used for exon amplification in
      preliminary mutation analysis during an attempt to identify a gene responsible
      for a disease. We propose a simple approach to find a short region from a genomic
      sequence that with high probability overlaps with some exon of the gene. The
      algorithm is enhanced to find one or more segments that are probably contained in
      the translated region of the gene and can be used as PCR primers to select
      appropriate clones in cDNA libraries by selective amplification. The algorithm is
      further extended to locate a set of PCR primers that uniformly cover all
      translated regions and can be used for RT-PCR and further sequencing of (unknown)
      mRNA.

PMID- 9520498
TI  - GenXref. VI: Automatic generation of links between two heterogeneous databases.
AB  - MOTIVATION: A large proportion of the information found in public databases is
      not sufficiently cross-referenced. We developed genXref, an automated system for
      link inference, because embarking on a manual cross-referencing of genome data
      would require too much expensive human expertise. It uses information retrieval
      technology to generate links between objects of heterogeneous databases. RESULTS:
      GenXref was used to generate links between GDB genes and Genbank human sequences.
      It resulted in > 10,000 links with a precision of 83% and a recall of
      approximately 32%.

PMID- 9520499
TI  - Bayesian adaptive sequence alignment algorithms.
AB  - The selection of a scoring matrix and gap penalty parameters continues to be an
      important problem in sequence alignment. We describe here an algorithm, the
      'Bayes block aligner, which bypasses this requirement. Instead of requiring a
      fixed set of parameter settings, this algorithm returns the Bayesian posterior
      probability for the number of gaps and for the scoring matrices in any series of
      interest. Furthermore, instead of returning the single best alignment for the
      chosen parameter settings, this algorithm returns the posterior distribution of
      all alignments considering the full range of gapping and scoring matrices
      selected, weighing each in proportion to its probability based on the data. We
      compared the Bayes aligner with the popular Smith-Waterman algorithm with
      parameter settings from the literature which had been optimized for the
      identification of structural neighbors, and found that the Bayes aligner
      correctly identified more structural neighbors. In a detailed examination of the
      alignment of a pair of kinase and a pair of GTPase sequences, we illustrate the
      algorithm's potential to identify subsequences that are conserved to different
      degrees. In addition, this example shows that the Bayes aligner returns an
      alignment-free assessment of the distance between a pair of sequences.

PMID- 9520500
TI  - Comparative accuracy of methods for protein sequence similarity search.
AB  - MOTIVATION: Searching a protein sequence database for homologs is a powerful tool
      for discovering the structure and function of a sequence. Two new methods for
      searching sequence databases have recently been described: Probabilistic Smith
      Waterman (PSW), which is based on Hidden Markov models for a single sequence
      using a standard scoring matrix, and a new version of BLAST (WU-BLAST2), which
      uses Sum statistics for gapped alignments. RESULTS: This paper compares and
      contrasts the effectiveness of these methods with three older methods (Smith
      Waterman: SSEARCH, FASTA and BLASTP). The analysis indicates that the new methods
      are useful, and often offer improved accuracy. These tools are compared using a
      curated (by Bill Pearson) version of the annotated portion of PIR 39. Three
      different statistical criteria are utilized: equivalence number, minimum errors
      and the receiver operating characteristic. For complete-length protein query
      sequences from large families, PSW's accuracy is superior to that of the other
      methods, but its accuracy is poor when used with partial-length query sequences.
      False negatives are twice as common as false positives irrespective of the search
      methods if a family-specific threshold score that minimizes the total number of
      errors (i.e. the most favorable threshold score possible) is used. Thus,
      sensitivity, not selectivity, is the major problem. Among the analyzed methods
      using default parameters, the best accuracy was obtained from SSEARCH and PSW for
      complete-length proteins, and the two BLAST programs, plus SSEARCH, for partial
      length proteins.

PMID- 9520501
TI  - Combining evidence using p-values: application to sequence homology searches.
AB  - MOTIVATION: To illustrate an intuitive and statistically valid method for
      combining independent sources of evidence that yields a p-value for the complete
      evidence, and to apply it to the problem of detecting simultaneous matches to
      multiple patterns in sequence homology searches. RESULTS: In sequence analysis,
      two or more (approximately) independent measures of the membership of a sequence
      (or sequence region) in some class are often available. We would like to estimate
      the likelihood of the sequence being a member of the class in view of all the
      available evidence. An example is estimating the significance of the observed
      match of a macromolecular sequence (DNA or protein) to a set of patterns (motifs)
      that characterize a biological sequence family. An intuitive way to do this is to
      express each piece of evidence as a p-value, and then use the product of these p
      values as the measure of membership in the family. We derive a formula and
      algorithm (QFAST) for calculating the statistical distribution of the product of
      n independent p-values. We demonstrate that sorting sequences by this p-value
      effectively combines the information present in multiple motifs, leading to
      highly accurate and sensitive sequence homology searches.

PMID- 9520502
TI  - Combinatorial pattern discovery in biological sequences: The TEIRESIAS algorithm.
AB  - MOTIVATION: The discovery of motifs in biological sequences is an important
      problem. RESULTS: This paper presents a new algorithm for the discovery of rigid
      patterns (motifs) in biological sequences. Our method is combinatorial in nature
      and able to produce all patterns that appear in at least a (user-defined) minimum
      number of sequences, yet it manages to be very efficient by avoiding the
      enumeration of the entire pattern space. Furthermore, the reported patterns are
      maximal: any reported pattern cannot be made more specific and still keep on
      appearing at the exact same positions within the input sequences. The
      effectiveness of the proposed approach is showcased on a number of test cases
      which aim to: (i) validate the approach through the discovery of previously
      reported patterns; (ii) demonstrate the capability to identify automatically
      highly selective patterns particular to the sequences under consideration.
      Finally, experimental analysis indicates that the algorithm is output sensitive,
      i.e. its running time is quasi-linear to the size of the generated output.

PMID- 9520503
TI  - SplitsTree: analyzing and visualizing evolutionary data.
AB  - MOTIVATION: Real evolutionary data often contain a number of different and
      sometimes conflicting phylogenetic signals, and thus do not always clearly
      support a unique tree. To address this problem, Bandelt and Dress (Adv. Math.,
      92, 47-05, 1992) developed the method of split decomposition. For ideal data,
      this method gives rise to a tree, whereas less ideal data are represented by a
      tree-like network that may indicate evidence for different and conflicting
      phylogenies. RESULTS: SplitsTree is an interactive program, for analyzing and
      visualizing evolutionary data, that implements this approach. It also supports a
      number of distances transformations, the computation of parsimony splits,
      spectral analysis and bootstrapping.

PMID- 9520505
TI  - Design and implementation of a qualitative simulation model of lambda phage
      infection.
AB  - MOTIVATION: Molecular biology databases hold a large number of empirical facts
      about many different aspects of biological entities. That data is static in the
      sense that one cannot ask a database 'What effect has protein A on gene B?' or
      'Do gene A and gene B interact, and if so, how?'. Those questions require an
      explicit model of the target organism. Traditionally, biochemical systems are
      modelled using kinetics and differential equations in a quantitative simulator.
      For many biological processes however, detailed quantitative information is not
      available, only qualitative or fuzzy statements about the nature of interactions.
      RESULTS: We designed and implemented a qualitative simulation model of lambda
      phage growth control in Escherichia coli based on the existing simulation
      environment QSim. Qualitative reasoning can serve as the basis for automatic
      transformation of contents of genomic databases into interactive modelling
      systems that can reason about the relations and interactions of biological
      entities.

PMID- 9520504
TI  - Xlandscape: the graphical display of word frequencies in sequences.
AB  - MOTIVATION: To provide a graphical interface for the generation, display and
      manipulation of a sequence landscape that will run on all X-windows-based Unix
      workstations. RESULTS: The sequence landscape approach enables the representation
      of the frequency of occurrence of all query sequence sub-words within a database.
      The landscape approach can detect tandem and other repeating word motifs,
      specific sub-words that are over-represented words in a particular database using
      Markov probability and the preference for sub-words belonging to either one of
      two databases. All these features aid in the classification of a query sequence.
      Given the open-text format for sequences and databases, the Xlandscape tool can
      be applied to a wide range of problems.

PMID- 9520506
TI  - Trace alignment and some of its applications.
AB  - MOTIVATION: Extra useful information can be extracted from a DNA chromatogram
      trace, over that contained in the base-called DNA sequence. Many sequencing
      applications can benefit from examination of these traces. RESULTS: An algorithm,
      based on dynamic programming, for aligning a DNA chromatogram to a DNA sequence
      is described and implemented. Its applications to vector clipping, EST alignment
      and mutation detection are discussed.

PMID- 9520507
TI  - Spectrum: spectral analysis of phylogenetic data.
AB  - MOTIVATION: Spectrum is a new Macintosh and Microsoft Windows program designed to
      read in phylogenetic four-state or binary data in NEXUS format, and output the
      corresponding bipartition spectra. It can be used to find the tree whose expected
      spectrum is closest to the observed spectrum (the closest tree, Hendy, Discr,
      Math., 96, 51-58,. 1991).

PMID- 9520508
TI  - Assistive technology: funding options and strategies.

PMID- 9520509
TI  - Networking forum for lawyers with disabilities and lawyers who practice
      disability law: summary report. Report from the Commission's Subcommittee on
      Lawyers with Disabilities.

PMID- 9520510
TI  - The renin-angiotensin system--from Tigerstedt to Goldblatt to ACE inhibition and
      beyond.

PMID- 9520511
TI  - The renin-angiotensin system revisited: classical and nonclassical pathway of
      angiotensin formation.

PMID- 9520512
TI  - Left ventricular hypertrophy in hypertension: etiology, treatment, and
      controversies.

PMID- 9520513
TI  - Angiotensin II and cardiac remodeling.

PMID- 9520514
TI  - Vascular hypertrophy in hypertension: role of the renin-angiotensin system.
AB  - Angiotensin II is vasoconstrictor and antinatriuretic; it also stimulates cell
      growth and proliferation in vascular smooth muscle, resulting in hypertrophy or
      hyperplasia of conduit and resistance vessels. These actions are mediated through
      angiotensin II receptors (AT1 subtype), which activate several G-protein
      dependent intracellular transduction pathways, such as the phospholipase C,
      diacylglycerol and inositol trisphosphate the mitogen-activated protein (MAP)
      kinase pathway, and Janus kinase (JAK)-signal transducers and activators of the
      transcription (STAT)-mediated pathway. These can all increase the expression of
      certain proto-oncogenes, particularly c-fos. Angiotensin II also stimulates the
      activity of certain growth factors, such as platelet-derived growth factor-A
      chain and basic fibroblast growth factor. The cellular responses to angiotensin
      II in vascular smooth muscle have been shown in different hypertensive vessels to
      be either hypertrophy alone, hypertrophy and DNA synthesis without cell division
      (polyploidy), or DNA synthesis with cell division (hyperplasia). In genetic
      hypertension, there is either cellular hyperplasia or remodeling, whereas in
      renovascular hypertension, there is hypertrophy of vascular smooth muscle cells.
      Angiotensin-converting enzyme (ACE) inhibitors prevent or reverse vascular
      hypertrophy in animal models of hypertension. In human hypertension, ACE
      inhibitors reduce the increased media/lumen ratio of large and small arteries and
      increase arterial compliance. These properties are also shared by AT1 receptor
      antagonists. The implications of these findings for morbidity and mortality in
      hypertension still await rigorous testing in prospective clinical trials.

PMID- 9520515
TI  - The renin-angiotensin system as a mediator of renal injury in hypertension.

PMID- 9520516
TI  - Preventing and reversing target organ damage by treatment of the renin
      angiotensin system.

PMID- 9520517
TI  - Antagonizing excitotoxicity: a therapeutic strategy for stroke?

PMID- 9520518
TI  - Immunoglobulin and IgG subclass levels in the African American and Hispanic
      populations of east Harlem.
AB  - BACKGROUND: The normal levels of immunoglobulin and IgG subclasses in African
      American and Hispanic populations are uncertain. To determine immunoglobulin and
      IgG subclass levels in this community, we measured serum IgG, IgM, and IgA levels
      along with IgG subclasses in 303 African American and Hispanic patients in a
      general medical clinic and an allergy/asthma clinic in East Harlem in New York
      City. METHODS: Prospective measurement of immunoglobulins and IgG subclasses in a
      general medical clinic and an allergy/asthma clinic in East Harlem. RESULTS: Ten
      (3.4%) patients had IgG levels below the lower limit of normal values, two
      (0.07%) patients had IgA levels below the lower limit of normal values, and two
      (0.07%) patients had an IgM level below the lower limit of normal values. Twenty
      four (8.1%) patients had IgG subclass levels below the lower limit of normal
      values; 1 patient had low levels of IgG1 and IgG3, 5 patients had low levels of
      IgG2, and 18 patients had low levels of IgG3. Because low IgG subclasses and
      allergy/asthma appeared to be associated, we compared IgG subclass levels of the
      patients with and without allergy/asthma. The mean IgG2 level in the patients
      without allergy/asthma was 425.1 +/- 199.1 mg/dL (p = 0.05) compared with 345.5
      +/- 133.1 mg/dL in the allergy/asthma group, the mean IgG3 level in the patients
      without allergy/asthma was 85.0 +/- 57.1 mg/dL compared with 64 +/- 34.1 mg/dL in
      the allergy/asthma group (p = 0.016) but there were no differences in IgG1 and
      IgG4 levels between the two groups. CONCLUSION: Altogether, our data indicate
      that humoral immunoglobulin and IgG subclass levels below the lowest normal
      values occur in the low socioeconomic African American and Hispanic populations,
      especially in patients with asthma in East Harlem.

PMID- 9520520
TI  - In sickness and in health.

PMID- 9520519
TI  - Amaranthin lectin binding in the rat colon: response to dietary manipulation.
AB  - BACKGROUND: In human colon, binding of the lectin Amaranthus caudatus has been
      considered to be a marker of cellular proliferation and malignant progression. We
      studied regional amaranthin binding in rat colon and correlated this with
      physiologic manipulations of proliferation. METHODS: Binding of amaranthin in
      segments of proximal and distal colon was studied in starved, refed, and control
      Wistar rats and was compared to tritiated thymidine labeling and proliferating
      cell nuclear-antigen expression. RESULTS: Amaranthin bound mainly to cells in the
      lower crypt of distal colon and midcrypt of proximal colon, paralleling the
      distribution of proliferative markers. Binding occurred in the supranuclear
      region in distal colon and the pericellular membrane in proximal colon.
      Starvation/refeeding was associated with a change in amaranthin binding intensity
      in distal colon, but not in proximal colon. CONCLUSION: The pattern of amaranthin
      binding during starvation/refeeding seems to reflect physiologic changes in
      several areas of the colon.

PMID- 9520521
TI  - Reactive perforating collagenosis.

PMID- 9520522
TI  - An overview of mental health services for the elderly.
AB  - Psychiatric distress is substantially prevalent among elderly individuals,
      particularly in the primary care and institutional settings, where most older
      persons receive mental health care. Barriers to care from providers include
      negative attitudes and stigmatization and poor recognition by general health care
      professionals. When psychiatric disorders are recognized, the intensity and
      duration of treatment provided is generally below standards for adequacy. Further
      research can determine the impact of patient, caregiver, and provider factors on
      treatment provision and on patient adherence to treatment. Assessment of factors
      influencing the treatment process are needed to ensure that treatments provided
      in the real world approximate the efficacy established in controlled clinical
      trials.

PMID- 9520523
TI  - Late-life suicide and depression in the primary care setting.
AB  - Late-life depression and suicidal behavior in the primary care setting is a
      significant public health concern. The prevalence of depression in this
      population is substantial, yet rates of detection and treatment are far from
      adequate. Untreated depression has significant consequences with regard to
      morbidity and mortality. Although suicide is a relatively low-base-rate behavior,
      a substantial proportion of late-life suicides have contact with their primary
      care provider prior to their death; thus this offers an avenue for suicide
      prevention. There is a growing knowledge base concerning what constitutes
      barriers to the recognition and treatment of late-life depression as well as what
      constitutes useful screening tools and treatments for the depressed elderly.
      Important new findings with regard to the functional effects of subsyndromal
      depression, possible subtypes of late-life depression, the clinical utility of
      SSRIs and psychotherapeutic interventions, and innovative and collaborative
      models of care hold promise for advancing the science and practice of treating
      late-life depression.

PMID- 9520524
TI  - Early diagnosis of Alzheimer's disease.

PMID- 9520525
TI  - Psychoses: diagnosis and treatment in the elderly.

PMID- 9520526
TI  - Issues involved in assessing competency.
AB  - A psychiatric competency assessment entails more than merely conducting a few
      clinical tests to diagnose the cause of a cognitive impairment. The psychiatrist
      may need to explore other aspects of the patient's life, including his or her
      interpersonal relationships and functional abilities. To provide a truly useful
      consult for other physicians, legal professional, family members, and the
      patient, the psychiatrist must be able to integrate the medical findings along
      with all relevant personal information and apply this information to the legal
      standards of the particular jurisdiction. By being able to apply both medical and
      legal knowledge of proxy decision making, the psychiatrist will be better
      prepared to make recommendations that will facilitate the proper care and
      services for the cognitively impaired patient.

PMID- 9520527
TI  - ECT in the elderly.
AB  - Depression is a common clinical problem in the elderly. Risk factors in this
      population include genetic vulnerability, psychosocial losses, medical
      comorbidity, cerebrovascular disease, and neurodegenerative disorders. Depression
      in the elderly may have severe consequences, including high rates of suicide,
      malnutrition or dehydration, high utilization of medical services, impaired
      recovery from medical illnesses, and inappropriate placement in residential care
      facilities. A significant number of older depressed patients may not respond to
      anti-depressant medications, suffer intolerable medication side effects, or have
      illnesses with symptoms or consequences so severe that it is not feasible to wait
      the time required for one or more antidepressant trials to work. For many of
      these patients ECT can be a dramatically effective treatment. With appropriate
      evaluation and monitoring, ECT can be performed with relative safety even for
      patients with serious concurrent medical illnesses. Serious adverse effects are
      rare, and cognitive consequences of ECT are generally circumscribed and of
      limited duration; there is no evidence of "brain damage" or permanent change in
      cognitive ability from ECT. After a recovery period memory function is often
      better than it was during the episode of depression. For patients who have been
      refractory to or intolerant of medication, maintenance ECT can be an effective
      strategy for preventing early relapse. Further research is needed, however, to
      clarify the optimum use of MECT schedules and pharmacotherapy combinations to
      most effectively and safely prevent relapse of depression in different elderly
      populations and to help predict who will best respond to which treatment
      modalities.

PMID- 9520528
TI  - Update on the use of antidepressants in the elderly.
AB  - This chapter presents a review of the current status of depression treatment for
      the elderly. The authors describe currently available antidepressants and discuss
      special considerations when they are used to treat elderly patients.

PMID- 9520529
TI  - Treatment of agitation in dementia.
AB  - Agitation occurs commonly in patients with dementia. Before symptomatic
      pharmacotherapy is undertaken, it is imperative to perform a sequence of
      evaluations and interventions to establish whether simpler and safer,
      nonpharmacologic approaches will be beneficial. When psychotropic medications are
      used they should be used judiciously, in the lowest effective doses and for the
      shortest period of time necessary. Ineffective medications should be stopped, and
      even effective medications should be empirically tapered in most patients to
      learn whether treatment is still necessary. Antipsychotics probably show the
      greatest benefit for agitation associated with psychotic features; they have less
      demonstrated efficacy for agitation not associated with psychotic features. The
      side effects of typical agents are legion; data are pending regarding atypical
      agents. The available evidence regarding nonneuroleptic medications ranges from
      case reports to well-designed, double-blind, placebo-controlled, randomized,
      parallel group studies. Literature exists describing the use of anticonvulsants,
      anxiolytics, serotonergic antidepressants, and other agents to manage agitation.
      Carbamazepine and divalproex sodium (valproate) have demonstrated efficacy in
      uncontrolled studies, whereas the use of carbamazepine has produced negative
      results in one small controlled study and positive results in two larger
      controlled studies. Buspirone has shown benefit in some open trials. Encouraging
      early findings have been reported for trazodone, including from one controlled
      trial. Varying results have been obtained using selective serotonin reuptake
      inhibitors, but with consistently encouraging anecdotes. In the aggregate, the
      evidence suggests but does not prove that alternatives to traditional
      antipsychotics exist. Again, none of these agents has yet been approved for this
      purpose by the FDA. As more studies become available we will have a better idea
      about which classes of agents are most efficacious. It is likely that there may
      be a role for "rational" polypharmacy in the management of this distressing
      complication of dementia. However, no studies that we know of address combination
      therapy, so the clinician must contemplate this option on a case-by-case basis.
      Clinical trials data are pending from studies with divalproex sodium,
      carbamazepine, haloperidol versus trazodone versus placebo, risperidone,
      olanzapine, quetiapine, donepezil, xanomeline, tacrine, buspirone, and
      sertraline, at the very least. These data will undoubtedly have a major impact on
      how we care for our patients and lead to revisions of current practice
      guidelines.

PMID- 9520530
TI  - Relations among mock jurors' attitudes, trial evidence, and their selections of
      an insanity defense verdict: a path analytic approach.
AB  - This study examined an important question relevant to the domain of the insanity
      defense: What are the interrelationships among important evidential and
      attitudinal factors which influence how jurors decide their final verdicts? To
      answer this question, a mock trial in which the insanity defense was argued was
      presented to 224 college undergraduates by means of an audiotape and slide show.
      Following the presentation, participants were asked to answer a series of
      questions regarding the trial. A path model was specified with four evidential
      factors as endogenous variables, i.e., evaluation of the defendant's mental
      status, belief that the defendant could be rehabilitated, beliefs regarding the
      accuracy of the expert witnesses, and mock-jurors' predeliberation verdicts. In
      addition, three attitudinal factors were specified as exogenous variables, i.e.,
      attitudes toward the insanity defense, attitudes towards due process vs crime
      control, and attitudes towards the death penalty. The path model was consistent
      with previous literature, suggesting that jurors' attitudes toward the death
      penalty and the insanity defense had a direct effect on how they evaluated the
      accuracy of the expert testimony and their evaluation of the defendant's over-all
      mental status. In turn, mock jurors' evaluations of the defendant's mental status
      had a direct effect on their selections of verdict. Importantly, mock jurors'
      evaluations of the evidential factors, particularly the mental status of the
      defendant, were a stronger predictor of their selections of verdict than were
      their initial attitudes.

PMID- 9520531
TI  - Steroid use among Miami's public school students, 1992: alternative subcultures:
      religion and music versus peers and the "body cult".
AB  - This analysis examined self-reported use of steroids by 478 adolescents in Dade
      County, Florida public schools during 1992. Statistically significant factors
      which tended to increase the probability of steroid use by adolescents included
      peer use of steroids, being male, and residing either with their mothers or on
      their own. The only statistically significant variables which are negatively
      related to steroid use are that religion is an important part of their lives and
      that students are involved in musical activities at school.

PMID- 9520532
TI  - Eating attitudes in female college students with self-reported alexithymic
      characteristics.
AB  - Several studies have indicated that there is a close relationship between eating
      attitudes and alexithymic characteristics. In this study, the influence of
      parental bonding on the association of alexithymic characteristics and eating
      attitudes was examined in a sample of 580 college students. Multivariate analyses
      of variance indicated that female students with two alexithymic characteristics,
      difficulty identifying feelings and difficulty describing feelings, exhibited
      more abnormal eating attitudes (poor oral control). Multivariate analysis of
      covariance gave significant associations with maternal care. Although these
      subjects were not patients with eating disorders the results suggest that the two
      alexithymic characteristics studied were associated with lack of maternal care
      and are a risk factor for eating disorders.

PMID- 9520533
TI  - Development of the Alexithymia Scale for Children: a preliminary study.
AB  - The Alexithymia Scale for Children-Teacher Form was developed with a sample of
      286 elementary schoolchildren. The validity and reliability of the measure were
      supported by factor analytic structure, relatively high internal consistency,
      test-retest correlation over 2 mo., and correlations of .24 to .39 with scores on
      the Yatabe-Guilford Personality Test. Factor analysis yielded two factors related
      to alexithymia, Difficulty in Describing Feelings and Difficulty Relating to
      Others. Alexithymia constructs such as a paucity of fantasy life and externally
      oriented thinking were not recorded.

PMID- 9520534
TI  - Suicide rates in immigrants.
AB  - The suicide rates of 12 immigrant groups in the USA in 1959 were not associated
      with the size of those immigrant groups in the American population.

PMID- 9520535
TI  - Difficulties in the understanding of false belief: specific to autism and other
      pervasive developmental disorders?
AB  - The present study examined the performance on a false belief task of atypical
      autistic children, i.e., children with a pervasive developmental disorder not
      otherwise specified (n = 50), socially immature children (n = 50), and normal
      children (n = 50). Children were shown a chocolate box and its unexpected
      content, i.e., a pencil, and then required to indicate what a friend would say
      about the content of the box. Results can be summarized: (1) over-all, 3-year-old
      children performed less well than children of 6 years. (2) Responses of 3-year
      old atypical autistic and socially immature children did not differ significantly
      from those of normal children of the same age. (3) At age 6, normal children
      performed better than atypical autistic and socially immature children. (4) In
      general, no differences in performance between atypical autistic and socially
      immature children were found, and (5) their performance was linked to
      intelligence. The results support prior findings that atypical autistic children
      find it difficult to understand false beliefs; however, this difficulty does not
      seem to be specific for (atypical) autism, but might be a common feature of
      social immaturity in general.

PMID- 9520536
TI  - Families and parenting: a comparison of lesbian and heterosexual mothers.
AB  - Mothers (24 lesbian and 35 heterosexual) were asked to complete a questionnaire
      of four scales, Index of Family Relations, Index of Parental Attitudes, Family
      Awareness Scale, and Dyadic Adjustment Scale. Analysis of the mean scores
      indicated that these lesbian and heterosexual mothers gathered in a snowball
      sampling had remarkably similar scores on self-reported stress, adjustment,
      competence, and quality of the relationship with their families, although
      variability was larger for the lesbian group.

PMID- 9520537
TI  - Locus of control and occupational stress in Chinese professionals.
AB  - The relationship between scores on locus of control, occupational stress, and
      stress symptoms was examined in 189 Hong Kong Chinese professionals. Scores on
      locus of control were associated with occupational stress and psychological
      stress symptoms but were unrelated to reporting of physical symptoms. While both
      sexes reported similar occupational stress, women scored as more External and
      reported more of both types of symptoms. The implications of the results were
      discussed.

PMID- 9520538
TI  - Alcohol consumption and sexual victimization among college women.
AB  - 842 women enrolled in large health classes offered at a midwestern university
      completed a health survey from which report of both the women's drinking behavior
      and their experience with sexual victimization could be excerpted. Both
      correlations and analysis of variance indicated an association between the amount
      of alcohol the women reported drinking each week and their over-all experiences
      with sexual coercion.

PMID- 9520539
TI  - Attitudes toward physician-assisted suicide.
AB  - Personality test scores (psychoticism, neuroticism, and extraversion) were not
      associated with attitudes toward physician-assisted suicide in a sample of 50
      undergraduate students.

PMID- 9520540
TI  - A profile of sexual health behaviors among college women.
AB  - This study examined the risk taking and preventive behaviors related to sexually
      transmitted diseases among sexually active college women. Self-report
      questionnaires were distributed at two mid-Atlantic universities yielding a final
      sample of 556 students. Data were collected regarding frequencies of pelvic
      examinations, numbers of vaginal, oral, and anal sex partners, and number of
      partners who had forced sex against their will. Also, frequencies of tests for
      sexually transmitted disease and HIV before having sex with new partners, methods
      of protection and birth control, and types of relationships were assessed.
      Finally, subjects reported the types of questions asked before having sex with a
      new partner and diagnoses of sexually transmitted diseases. Because most college
      aged women are sexually active and vulnerable to a host of short- and long-term
      complications from sexually transmitted infections, educational interventions, in
      addition to promoting condom use, must focus on the need for regular pelvic
      examinations, screenings for sexually transmitted disease/HIV (self and partner),
      and lower risk sexual activity.

PMID- 9520541
TI  - Differential staff perceptions of service organization and management in drug
      treatment.
AB  - Dissonance among 23 professional and 7 paraprofessional staff of drug service
      agencies toward case record management of addicts was investigated. Analysis
      showed that these paraprofessionals, former drug addicts now in a treatment role,
      tend to be more critical of how case records are dealt with than professional
      staff. The data favour the hypothesis that the greater the diversity of staff's
      background characteristics, the greater are the chances for disagreement and
      discord in organization and management.

PMID- 9520542
TI  - Media messages and alcohol education: a school-based study.
AB  - The immediate effects of a media intervention on attitudes toward alcohol were
      investigated with 134 secondary school pupils (aged 13 to 17 years) who completed
      a drinking and smoking questionnaire and expressed strength of agreement or
      disagreement with 13 statements about alcohol, drinking and health. Pupils then
      read news cuttings from popular magazines. One group read a negative message
      about alcohol, another group a positive message. Other groups read both positive
      and negative messages, and a control group had no media intervention. Immediately
      afterwards, all pupils responded to the same 13 statements again. Those pupils
      who received only a negative message became significantly more negative in their
      attitudes towards alcohol. Those receiving only a positive message were
      significantly more positive afterwards. The control group and those receiving
      both positive and negative messages showed little change. These findings are
      discussed in terms of their implications for alcohol education programs at
      school.

PMID- 9520543
TI  - Circaseptennian (about 7-year) periodicity in the distribution of birth years of
      Nobel laureates for physics.
AB  - The distribution of birth years for Nobel physicists shows a circaseptennian
      (about 7-year) periodicity. This observation extends an earlier observation of a
      circaseptennian pattern in the distribution of birth years for early quantum
      physicists. In both categories, birth rate tends to maximize in years belonging
      to the (7n + 4) phase.

PMID- 9520544
TI  - Depressive symptoms and HIV-risk behavior in inner-city users of drug injections.
AB  - The association of HIV risk-taking behavior with frequency of depressive symptoms
      varied by specific risk behavior and amount of harm reduction of behavior of men
      and women (N = 642), 80% of whom were African-American.

PMID- 9520545
TI  - Cognitive progress associated with gambling behaviour.
AB  - Gambling behaviours can be pathological if positive response is extreme, but very
      little is known about the psychological precursors of pathological gambling in
      Australia. This study examined the relationships between self-reported gambling
      behaviours and scores on locus of control measures. The sample of 80 male and 75
      female undergraduate students completed the South Oaks Gambling Screen and
      Levenson's multidimensional Locus of Control Scale. No significant association
      was found for the self-reported gambling behaviours with scores on the Internal
      scale but a positive one obtained between scores on the Powerful Others subscale.
      Self-reported gambling behaviours differed significantly for men reported that
      they gambled more than women. For these Australian undergraduates an additional
      question on borrowing money increased the apparent frequency of pathological
      gambling. Thus an avenue for further research is the development of a valid and
      reliable measure of gambling behaviours in an Australian sample.

PMID- 9520546
TI  - Unionization and rates of personal violence (suicide and homicide).

PMID- 9520547
TI  - Irrational beliefs and marital conflict.
AB  - To test the hypothesis that the major irrational evaluative beliefs postulated by
      Rational Emotive Behavior Therapy are related to marital conflict, 15 married
      couples participated in a thought-listing procedure. During this procedure, three
      idiosyncratic scenes portraying marital conflict and three control scenes free of
      conflict were identified for and presented to each member of the dyad. Analysis
      indicated that the conflict-portraying scenes were associated with significantly
      more irrational evaluative beliefs and significantly fewer rational cognitions
      than the control scenes.

PMID- 9520548
TI  - Role-play gamers and National Guardsmen compared.
AB  - Scores of 54 fantasy role-game players and 64 National Guardsman were compared on
      a neuroticism scale and demographic variables. While the Role-gamers reported
      daydreaming and sleeping more than the Guardsmen, the popular stereotype that
      game players are withdrawn, emotionally immature adolescents was not confirmed.
      The typical game player was male with as many close friends as the guardsmen.
      Mean neuroticism scores did not appear to differ between the two groups and were
      not high enough to be considered clinically significant.

PMID- 9520549
TI  - Reliabilities of human judgements: measurements from photographic CT scan images.
AB  - Studies of brain lesions are generally dependent on human judgement for
      identification and possibly for measurement, but estimates of reliability are
      frequently neglected. The present study involves three investigation based on X
      ray CT scans into reliabilities of human judgements: (1) the areas of brain
      lesions identified over two occasions by a single judge, (2) brain areas based on
      the projection of scans by a second judge over two occasions, and (3) brain areas
      computed from brain outlines by two independent judges. Errors decreased
      geometrically over procedures in the order listed, reflecting the decreasing
      complexity of judgement involved. Nevertheless, all three reliabilities proved
      satisfactory, showing that these procedures may be applied consistently over
      occasions and between raters. This was reassuring since computerization is
      currently practicable only in (2) and (3), where errors were least. Although not
      always performed, reliability checks are important, as indicated by the outlier,
      Case 10. Where there is a large discrepancy, seeking the reason(s), with a view
      to standardizing the criteria of judgement, is preferable to automatic averaging,
      both as a safeguard in individual cases and also to estimate error of measurement
      in group studies. To assist decision in any particular instance as to whether
      averaging is an acceptable solution, a statistical rule of thumb is proposed for
      testing the significance of the difference between two judgements.

PMID- 9520550
TI  - Personalities of players of Dungeons and Dragons.
AB  - 20 men who played Dungeons and Dragons did not differ in mean scores on
      depression, suicidal ideation, psychoticism, extraversion, or neuroticism from
      unselected undergraduates.

PMID- 9520551
TI  - Preliminary study of tolerance of ambiguity of individuals reporting paranormal
      experiences.
AB  - This research tested the notion that poltergeist-like experiences reflect the
      need to explain anomalous personal experiences. Thus, it was hypothesized that
      percipients of poltergeists would score lower on tolerance of ambiguity than
      controls. Further, it was hypothesized that tolerance of ambiguity would
      negatively correlate with the number of different categories of poltergeist
      experience. 30 self-identified percipients of poltergeist-like phenomena and 30
      self-identified nonpercipients of the paranormal were administered the Rydell
      Rosen Ambiguity Tolerance Scale and Houran and Lange's Poltergeist Experiences
      Checklist. Results partially supported predictions. Percipients of the paranormal
      scored significantly lower on tolerance of ambiguity than nonpercipients, but
      scores on the experiences checklist did not significantly correlate with scores
      on tolerance of ambiguity. The results supported the main hypothesis but more
      detailed research is needed to clarify the roles of age and tolerance of
      ambiguity in the perception of anomalous phenomena.

PMID- 9520552
TI  - Sex and sex-role differences in locus of control.
AB  - The relations among of sex, measures of sex-role orientation, and locus of
      control were examined with 240 undergraduates (150 women and 90 men). Although
      there were no sex differences on mean locus of control scores, a significant
      relation between scores on sex-role orientation and locus of control was observed
      for women but not for men.

PMID- 9520553
TI  - Pets as transitional objects: their role in children's emotional development.
AB  - Children's use of pets as transitional objects and the contributions of pets to
      children's emotional well-being were examined. The sample included 94 boys and 80
      girls in preschool through Grade 5; 70% were current pet owners, and 30% were not
      pet owners. Each participant was individually interviewed using a structured
      interview format of 20 questions for current pet owners and three questions for
      non-pet owners to assess perceptions about the role of friendships between
      animals and humans, shared activities between children and pets, ways animals and
      humans communicate love for one another, types of verbal and nonverbal
      communication and interactions between animals and humans, and ways animals
      provide love, security, and emotional support to humans. Analysis indicated that
      children perceive their pets as special friends, important family members, and
      providers of social interactions, affection, and emotional support. Results are
      discussed in terms of the parallels between children's use of inanimate
      transitional objects and their use of pets as transitional objects.

PMID- 9520554
TI  - Sexual knowledge, behaviors, and attitudes of medical students in Kunming, China.
AB  - 422 medical students at a conservative campus in Yunnan reported their sexual
      knowledge, behaviors, and attitudes of reproductive health service to help
      students acquire necessary sexual knowledge and avoid unwanted pregnancy,
      abortion, and sexually transmitted diseases.

PMID- 9520555
TI  - Feedback, test anxiety and performance in a college course.
AB  - The effects of three forms of test feedback and text anxiety on test performance
      were examined within the context of a self-paced, criterion-based course in
      educational psychology. 73 undergraduate students completed seven units of work
      and were evaluated by computer-administered unit tests. Students were randomly
      assigned to one of three test feedback forms: (1) item-by-item knowledge of
      responses, (2) answer-until-correct, and (3) delayed feedback. Students received
      their assigned feedback during the first two units, after which they were allowed
      to choose. Test anxiety was measured prior to testing on Sarason's Test Anxiety
      Scale and during testing on an item administered by the computer program.
      Students who reported high test anxiety on the Test Anxiety Scale experienced
      more anxiety during testing than students reporting low test anxiety. Anxiety
      during testing was not related to type of feedback, and the two variables were
      not related to course performance on the second unit. Data collected at the
      conclusion of the semester indicated that students who reported higher test
      anxiety required more attempts to pass unit tests than those reporting lower test
      anxiety. Given a choice, students preferred answer-until-correct feedback. This
      preference was not related to Test Anxiety Scale scores. Anxiety during testing
      was not related to being allowed to choose forms of feedback.

PMID- 9520556
TI  - Correlations between scores on Chinese versions of long and short forms of the
      Geriatric Depression Scale among elderly Chinese.
AB  - A total of 187 elderly Chinese from the community were interviewed with the
      Chinese versions of the Geriatric Depression Scale-the long form and the short
      form. The scores on a proposed new version of the short form were also
      calculated. Cronbach alpha for the Geriatric Depression Scale-long form was .86.
      The correlations were significant between scores on the long and short forms (r =
      .94, p < .05) and between these on the long and new short forms (r = .91, p <
      .05). Cronbach coefficient alpha for the short form was .77 and for the new short
      form .81. Results of our study indicated that responding by these elderly persons
      on both short forms is acceptably internally consistent in comparison with those
      on the original Geriatric Depression Scale.

PMID- 9520557
TI  - An academic paradox: high school students' perceptions of their class standing
      and self-reported risk-taking.
AB  - The centers for Disease Control and Prevention (CDC) administered its 75-item
      1991 Youth Risk Behavior Surveillance survey to a nationwide random sample of
      12,248 high school students. In a secondary analysis of their data, one item on
      students' perceived class standing, was compared with selected health risk-taking
      practices. The 7.7% of students who indicated that they were "below the middle"
      in comparison with their classmates reported more participation in all risk
      taking behaviors than students who reported being "in the middle" (28.6%) or
      "above the middle" (63.7%). Students' grades, ages, and ethnicity showed
      significant differences, with younger students and selected ethnocultural
      minority students more likely to report being "below the middle." Perceived class
      standing may be a proxy measure for estimating participation in health
      compromising practices.

PMID- 9520558
TI  - Personification of death in Ghanaian death notices.
AB  - Analysis of content of death notices (obituaries, in memoriams, and funeral
      announcements) may offer some explanation of how Ghanaians express their feelings
      about the death of loved ones and the meanings they assign to death and dying.
      Analysis of 371 death notices selected from two widely read Ghanaian newspapers,
      the Daily Graphic and the Ghanaian Times yielded six thematic expressions about
      death and dying: death is personified as cold and unfeeling and described as an
      ongoing painful experience: the deceased is described as beloved, devoted, and
      valued. Death notices indicate impending restructured roles and social
      relationships survivors face; the image and personality of the deceased are
      included; and the availability and proximity of the deceased's next of kin can be
      inferred. The findings add to the literature on (1) cultural attitudes toward
      death and (2) how death is managed and feelings about death and dying are
      expressed.

PMID- 9520559
TI  - Symptomatology and insight in schizophrenia.
AB  - The phenomenon of poor insight of clients with schizophrenia has recently
      received a great deal of attention; however, the relationship of the symptoms of
      illness and of poor insight is not fully understood. This study examined the
      relationship between ratings of symptomatology and ratings of insight deficits
      for 64 clients with schizophrenia. Symptomatology and insight were evaluated
      using the Positive and Negative Syndrome Scale. Over-all functioning was
      evaluated using the Global Assessment of Functioning scale. Ratings on positive
      symptomatology were significantly related to ratings of poor insight. As ratings
      of poor insight increased, ratings on severity of positive symptoms, for example,
      delusions and hallucinations, also increased Implications of this finding are
      discussed.

PMID- 9520560
TI  - Attitudes toward gun control and personality.
AB  - In a sample of 65 undergraduates, a negative attitude toward guns was associated
      with lower scores on Psychoticism.

PMID- 9520561
TI  - Psychosocial predictors of interest in prenatal genetic screening.
AB  - The purpose of the study was to identify psychosocial predictors of interest in
      prenatal genetic testing. Analysis of data from 886 responses in the 1996
      Louisville Metropolitan Survey indicate that factors such as demographic
      characteristics and scores on health locus of control that predict utilization of
      other preventive health care are less applicable to predicting attitudes toward
      genetic testing. Regression analyses indicated that political orientation,
      identification with religion, and attitudes against abortion predicted less
      favorable responses to a question about prenatal genetic testing. Abortion
      attitudes were particularly strong indicators of respondents' stated interests in
      testing. The findings have practical implications in terms of promoting
      preventive health care. Personal values may lead individuals to believe that
      prenatal testing leads to the intention of abortion.

PMID- 9520562
TI  - Male and female differences in anxiety about statistics are not reflected in
      performance.
AB  - In two introductory statistics courses (consisting of 70 women and 28 men over
      all), women indicated significantly more anxiety about taking the course than
      men, but performed as well as the men in both courses.

PMID- 9520563
TI  - Internal consistency of an Arabic Adaptation of the Beck Depression Inventory in
      four Arab countries.
AB  - An Arabic version of the revised edition of the Beck Depression Inventory in its
      complete form was developed. Back translation indicated the translation into
      modern standard Arabic was adequate. The cross-language equivalence of scores on
      the Arabic and English forms was .96, denoting high equivalence in meaning.
      Coefficients alpha were computed for samples of male and female undergraduates
      recruited from Egypt, Saudi Arabia, Kuwait, and Lebanon (ns = 100, 80, 100, 100,
      respectively). Values of alpha were .77, .82, .89, and .67, respectively. By and
      large, the inventory seems viable in the Arabic context so its use in cross
      cultural research may be explored.

PMID- 9520564
TI  - Factor structure of the Million Adolescent Personality Inventory for psychiatric
      inpatients.
AB  - A principal components factor analysis (with varimax rotation) was performed on
      the Millon Adolescent Personality Scale Base Rate scores of 335 adolescent
      psychiatric inpatients. A four-factor solution was obtained (accounting for 84.1%
      of the variance), which was similar to that obtained by Millon, et al, for the
      normative sample. Confirmatory factor analyses, however, using data obtained from
      computer generated random responses to the test, also fit the inpatient and
      normative sample data very well. The factor structure of the Millon Adolescent
      Personality Inventory therefore was inferred to be driven by the considerable
      item-scale overlap that characterizes the test.

PMID- 9520565
TI  - A review of the literature and a preliminary study of family compliance in a
      developmental disabilities clinic.
AB  - To investigate the compliance of family members with the treatment recommended
      for patients, three child and adolescent psychiatrists assessed the charts of all
      active outpatients in a developmental disabilities clinic in the psychiatric
      department of a tertiary care municipal hospital utilizing a Family Compliance
      Checklist, a survey form for chart review, in October, 1993 (n = 40), and in
      April, 1994 (n = 41). Almost no clients missed appointments over a 6-mo. period.
      Only one family refused to permit the use of medication. Three families refused
      to make appointments. The majority of the patients were Hispanic and almost half
      were Roman Catholic. We conclude that most families of patients in a
      developmental disabilities clinic comply with recommended treatment plans
      including scheduled appointments and prescribed medications.

PMID- 9520566
TI  - Verbal aggressiveness: conceptualization and measurement a decade later.
AB  - Verbally aggressive messages attack an individual's self-concept to inflict
      psychological pain. Infante and Wigley developed a trait measure of Verbal
      aggressiveness; however, the psychometric qualities and validity of the Verbal
      Aggressiveness scale were not fully explored. In Study I, 119 targets (Mage =
      46.2, SDage = 14.1) and 238 observers (Mage = 42.9, SD age = 14.4) participated.
      In Study II, 112 targets (Mage = 39.9, SDage = 12.9) and 236 observers (Mage =
      37.7 SDage = 11.1) participated. In Study III, 153 college students participated
      (Mage = 25.9, SDage = 4.6). In these studies, temporal stability over two months,
      criterion-related validity (target-observer agreement), discriminant validity
      (employing structural equation models), and construct validity (correlations with
      the facet and domain scales of the NEO-Personality Inventory-R) were
      investigated. The results justify considering Verbal Aggressiveness as a
      personality trait and the Verbal Aggressiveness scale as a valid measure.

PMID- 9520568
TI  - Age of onset and progress toward independent living by patients with chronic
      schizophrenia in a community based program.
AB  - For 11 women and 12 men age of onset of schizophrenia correlated .70 with
      progress in intensive treatment toward independent living.

PMID- 9520567
TI  - Age, sex, marital status and suicide: an empirical study of east and west.
AB  - The relationships among age, sex, marital status and suicidal behaviour in
      Australia and Hong Kong showed disparity in age-specific suicide rates among the
      four marital status groups, never married, married, widowed and divorced, for
      both sexes in the two locations. Examining the coefficients of preservation
      suggested the coefficient for never married to married in all cases was larger
      than 1, except for the groups of teenagers aged 15-19 years for both sexes and of
      elderly women aged 60 years or over in Hong Kong. The widowed or divorced groups
      have lower suicide rates than the married women among the elderly in Hong Kong.
      Hong Kong women seem not to have been benefited in marriage as much as men.
      Responsibility and workload in married life rather than low social status are the
      likely reasons for the relative high female suicide rate in Hong Kong. Possible
      cultural and environmental factors which are somewhat speculative (yet to be
      confirmed) are discussed.

PMID- 9520569
TI  - Knowledge of disease and dietary compliance in patients with end-stage renal
      disease.
AB  - Noncompliance is a common problem in patients with end-stage renal disease. In
      this study, we assessed the relationship between knowledge of disease and dietary
      compliance in a cohort of 56 dialysis patients. Based on a health belief model of
      adherence, we predicted that dialysis patients who knew more about kidney disease
      and its treatment would be more complaint than those who knew less about these
      matters. We also examined the relationship between dietary compliance and
      patients' emotional well-being. We used a composite measure of compliance
      consisting of serum K, P, and interdialytic weight gain. A 30-item "Kidney
      Disease Questionnaire" was used to assess patients' knowledge of their illness.
      Contrary to prediction, compliers did not score higher on the knowledge
      questionnaire; in fact, the observed correlation of .32 was in the opposite
      direction. In the same vein, we found no relationship between compliance and
      emotional well-being. These results, although somewhat surprising, add to a
      growing body of research which indicates that medical compliance involves more
      than educating patients about the mechanisms and treatment of their illness.

PMID- 9520570
TI  - Pupils' views on sex education in Transkei schools, South Africa.
AB  - Responses to a questionnaire of 49 girls and 28 boys, who ranged in age from 17
      to 29 years, suggested that pupils were favorable to sex education at schools as
      enhancing self-esteem, responsibility, and understanding of issues.

PMID- 9520571
TI  - Depressive experience and romantic relationships in young adulthood.
AB  - This study examined the associations between two factors of depressive experience
      (dependency and self-criticism) and satisfaction in adult romantic relationships.
      The Depressive Experiences Questionnaire, along with measures of attachment and
      relationship satisfaction, were administered to 107 men and 140 women attending
      local community colleges. Self-criticism was associated with global relationship
      distress and sexual dissatisfaction. In a combined regression equation, measures
      of self-criticism, attachment security, and attachment activation all contributed
      to predicting general relationship distress. Only scores on self-criticism
      predicted sexual dissatisfaction. The relationship dissatisfaction reported by
      those with high scores on self-criticism appears to be a relational aspect of the
      "destructiveness of perfectionism" described by Blatt.

PMID- 9520573
TI  - [Heroes and health].

PMID- 9520572
TI  - Suicide in Singapore by ethnic group, 1955-1984.
AB  - The association between measures of domestic integration and suicide rates for
      Singapore for 1955-1984 was found for Indians and "others" but not for Chinese
      and Malays.

PMID- 9520574
TI  - [When is analgesia to be prioritized?].

PMID- 9520575
TI  - [Epidemiology and hunting for the good life].

PMID- 9520576
TI  - [Prevention of osteoporosis-related fractures with alendronate].

PMID- 9520577
TI  - [Diagnostic DNA examinations].

PMID- 9520578
TI  - [Thyroid hormone resistance. Clinical, biochemical and genetic study of a
      family].
AB  - We here present a family where three individuals in three generations had varying
      degrees of goiter, tachycardia, fatigue, hyperactivity, and learning disability.
      Serum T3 and free T4 were elevated, whereas TSH was normal or slightly increased.
      The clinical findings in combination with the hormone values led to several
      supplementary investigations and therapies being carried out, but they had no
      beneficial influence on the patients' symptoms. The commonest form of thyroid
      hormone resistance (RTH) is an autosomal dominantly inherited disorder with
      varying degrees of hypo- and hyperthyroidism, including the hormonal changes
      described above. Several mutations, particularly in exons 9 and 10 of the thyroid
      hormone receptor beta gene, have been described and shown to be responsible for
      RTH. Exons 7, 8, 9, and 10 in the thyroid hormone receptor beta gene were
      amplified by polymerase chain reaction and analyzed by DNA sequencing. A
      heterozygous point mutation in nucleotide 1244 in exon 9 was demonstrated in the
      two patients with RTH that were available for the study. The guanidine to
      thymidine point mutation changed the codon for arginine in position 320 in the
      receptor protein to leucine. This mutation has previously been shown to decrease
      receptor affinity for T3; it has been demonstrated in some patients with RTH, and
      it is probably the cause of RTH in the family described in this study.

PMID- 9520579
TI  - [Bronchial ruptures are rare and should be surgically treated].
AB  - Bronchial rupture in blunt trauma is caused by sudden compression of the chest
      with dislocation of the lungs. The less pliant bronchi may thus rupture.
      Bronchial rupture is rare in patients admitted alive. Bronchial rupture has been
      diagnosed in two of the last 275 severe chest traumas admitted to Ulleval
      hospital since 1993 (0.7%). A 19-year-old male had total atelectasis of the lung
      19 days after the trauma. A four-year-old boy experienced total collapse of the
      lung and became critically ill the fourth day after initial normalisation of the
      chest X-ray. Both patients were successfully operated on, with reconstruction of
      the left main bronchus in both cases, after 29 and seven days, respectively. In
      the child an upper lobectomy was necessary. These patients illustrate that with
      expectative treatment in bronchial rupture, serious complications may be
      experienced.

PMID- 9520580
TI  - [Self-evaluation of knowledge and competence with regard to the treatment of
      pain].
AB  - In a survey completed at our hospital, 519 doctors and nurses were asked to
      evaluate their own knowledge and competence with regard to the treatment of
      various types of pain, including non-pharmacologic treatment methods. A total of
      473 responded to the questionnaire. In the study, cancer-related pain and pain
      from causes other than cancer were assessed in separate population groups. Of the
      doctors, 58% evaluated their knowledge of nociceptive pain as very good or fairly
      good. The corresponding findings for neuropathic pain were 31%, for psychological
      pain 27%, for social pain 25% and for spiritual and existential aspects of pain
      22%. The nurses scored lower than the doctors on knowledge and competence in
      relation to nociceptive and neuropathic pain (32% and 18% respectively), and
      higher on treatment of the psychological and social aspects of pain (44% and 36%
      respectively). Many of the doctors and nurses evaluated their knowledge as fairly
      poor or very poor with regard to nonpharmacologic treatment methods. In both
      professions 80% answered that depression was seen fairly often or very often
      among these patients.

PMID- 9520581
TI  - [Primary adrenal cortex insufficiency--a diagnostic challenge].
AB  - Primary adrenocortical insufficiency (Addison's disease) is characterised by
      weakness, tiredness, fatigue, weight loss, hypotension, hyperpigmentation and a
      craving for salt. Without treatment lethality is 100%; correctly treated, life
      expectancy is normal. Addison's disease may appear isolated or as part of a
      polyendocrine syndrome. Because several of the symptoms are unspecific and
      develop over the course of several years, many patients are not diagnosed before
      a life-threatening adrenal crisis develops. Autoimmune destruction of the adrenal
      cortex is the main cause of adrenocortical failure in the industrialised world.
      This condition is characterised by circulating autoantibodies against the
      steroidogenic enzyme 21-hydroxylase. These autoantibodies can now easily be
      quantified. More unusual causes of adrenocortical failure are tuberculosis,
      bleeding, metastasis and adrenoleukodystrophy. Using three cases we highlight the
      clinical, diagnostic and therapeutic aspects of adrenocortical failure.

PMID- 9520582
TI  - [Physiotherapy practice--examination and patient participation].
AB  - Musculoskeletal disorders are increasing; they require vast resources and are
      controversial. How are patients suffering from such disorders received, examined
      and understood? This article is based on a research project of first-time
      consultations in a physiotherapy practice, using video recordings and direct
      observations, supplemented by interviews. One particular encounter is described
      and analysed in detail. The analysis shows that most of the consultation was
      devoted to verbal communication and that the information obtained by verbal
      exchange and physical examination overlapped. The therapist stressed the
      relationship between the general state of the body and local conditions and
      regarded the body as a field of expression. Since the patient is affirmed as an
      experiencing body subject entitled to opinions, her participation is encouraged.
      A common ground for future co-operation is established. The findings emphasize
      the need for further analysis of actual practice and ist underlying assumptions.
      Microstudies of clinical consultations can teach us more about the relationship
      between diagnostics and the prerequisites for ensuring patients' participation.

PMID- 9520583
TI  - [Normal bone remodelling--what can go wrong in osteoporosis?].
AB  - The skeleton is a metabolically active organ in constant change and renewal.
      Specialised cells are responsible for resorbing and synthetizing bone matrix. The
      process of bone remodelling, by removing old and damaged bone tissue and
      replacing it with new, is necessary for conserving the integrity of bone. In
      recent years, research has given new insight into the fine relationship between
      different cell types in bone tissue. This has enhanced our understanding of the
      pathophysiology behind osteoporosis and other metabolical bone diseases. This
      article gives a summary of our present knowledge of the normal cell biology of
      bone and what contributes to its regulation. How this helps the understanding of
      normal and pathological bone loss is illustrated. It is important to understand
      bone remodelling in order to interpret measurements of bone mineral density and
      biochemical markers accurately.

PMID- 9520584
TI  - [Drug treatment of emotional and cognitive dysfunction in dementia].
AB  - The evaluation, treatment and care of patients with dementia are major tasks for
      the health service. This paper provides an overview of drug treatment of the
      emotional and cognitive disturbances of dementia. Tricyclic and the newer anti
      depressive agents are effective in patients with dementia and depression.
      Dopamine-blocking agents are effective for some patients with dementia and
      psychosis, but their use is limited by frequent and severe side-effects. Atypical
      neuroleptics may prove useful for this patient group. Aggression and agitation
      may be treated with serotonergic agents, neuroleptics, or benzodiazepines, but
      other strategies may also be useful. Cholinesterase-inhibitors have demonstrated
      efficacy on cognition and function, and may reduce the likelihood of
      institutionalization. Studies of possible stabilization therapies, such as
      trophic factors, propentophylline, and antiamyloid drugs, are reviewed. Recent
      reports suggesting a possible prophylactic effect of antioxidants, oestrogen, and
      antiinflammatory drugs are discussed. The substantial efforts now being made to
      discover effective drugs for dementia suggest that compounds that delay the
      disease progression may be available in the next 5-10 years.

PMID- 9520585
TI  - [Osteoporosis and fractures in Norway. Occurrence and risk factors].
AB  - Bone mass in the Norwegian population appears to be the lowest in Europe.
      Depending on which skeletal part is measured, from 14 to 36% of Norwegian women
      over the age of 50 suffer from osteoporosis according to the WHO definition. In a
      European multicentre study of the prevalence of vertebral deformities (the EVOS
      study), prevalence was the third highest among men and women from Oslo. Incidence
      rates of forearm and hip fractures are higher in Norway than in other countries.
      There are, however, differences in hip fracture incidence within Norway itself,
      with the highest rates occurring in urban areas. Body height is greater and body
      mass index lower than in other European countries. Vitamin D receptor allele
      polymorphism was found to have no influence on bone mass in two studies.

PMID- 9520586
TI  - [Can biochemical markers for bone density be recommended as diagnostic and
      prognostic tools in osteoporosis?].
AB  - Biochemical markers of bone metabolism have potential clinical value in
      osteoporosis, rheumatic diseases, metabolic bone diseases, and skeletal
      metastasis. The markers are measured in serum or urine and reflect bone synthesis
      or bone resorption. Knowledge of the markers' analytical and biological
      variation, sensitivity, and specificity is necessary to make use of these
      measurements. This article gives a review of the new bone markers available
      today: osteocalcin, bone alkaline phosphatase, procollagen peptides,
      pyridinolines, and telopeptides. Bone markers are clearly useful in research and
      in epidemiological studies, but routine clinical use is still controversial. We
      discuss the consequences of making use of bone markers in the diagnostics of
      osteoporosis, as a prognostic factor of bone loss or fractures, or to monitor
      therapy. We conclude that we still lack sufficient knowledge to justify use in
      clinical practice.

PMID- 9520587
TI  - [Estrogen replacement].
AB  - Recent research on long-term postmenopausal hormone replacement therapy (HRT)
      indicates a positive effect on both total mortality and morbidity. This has
      raised the question of widespread preventive long-term use of HRT. Possible side
      effects and ideological issues related to preventive HRT have led to debate and
      uncertainty among health professionals, in the media, and in the population at
      large. In order to evaluate the level of knowledge about and attitudes towards
      HRT, a randomly selected group of 737 Norwegian women aged 16-79 was interviewed
      by the Central Bureau of Statistics. One in three women had received information
      about HRT in the last two years, mainly through weekly magazines and physicians.
      The proportion who answered the questions on knowledge correctly varied from 36%
      to 47%. Those who had been given information by a physician possessed accurate
      knowledge, had more positive attitudes towards HRT and were more willing to use
      HRT than women who had reviewed information through other channels. Women with a
      higher level of education were better informed and more knowledgeable than
      others, but were nevertheless more reluctant to use HRT than those who were less
      educated. The limited number of women who actually receive information on HRT,
      the low level of knowledge and the ambivalent attitudes toward HRT are a major
      challenge to the public health service.

PMID- 9520588
TI  - [Hormone replacement therapy among Norwegian women. Self-reported use and sales
      of estrogen preparations].
AB  - In order to analyse the use of hormone replacement therapy (HRT) and the
      predicting factors for its use, two random samples of Norwegian women (30-79
      years) were interviewed by the Central Bureau of Statistics in 1994 (n = 565) and
      in 1996 (n = 470). The extent of use of HRT was compared with statistics for
      sales of oestrogen in Norway and the Nordic countries. In the age group 45-69
      years the use of hormone replacement therapy increased from 16.3% in 1994 to
      19.1% in 1996. The proportion of users did not increase with a higher level of
      education. In addition to information received, and after adjusting for other
      variables, attitudes towards oestrogen and knowledge about it were the most
      important contributing factors for using HRT. Sales figures show that the use of
      systemic oestrogen in Norway has increased more than 280% since 1990. None of the
      Nordic countries have had a corresponding increase, but the Norwegian figures are
      still low compared to most other Nordic countries. In 1996 14.5% of Norwegian
      women (50-79 years) used oestrogen for urogenital disorders. Norwegian women need
      to be better informed and more knowledgeable to enable them to make conscious
      choice regarding use of hormone replacement therapy.

PMID- 9520589
TI  - [The P-pill for men--when will it be available?].
AB  - Although the development of a hormonal contraceptive for men has proved to be
      more of a challenge than oral contraception for women, several experimental
      prototypes already satisfy many of the criteria that must be met. Steroid regimes
      are more effective in Asians than in men of other ethnic backgrounds. They are
      inexpensive, and the effect is reversible.GnRH analogues are promising, but
      further research is needed and is being carried out. Androgens must be used as a
      supplement to all hormonal strategies in order to maintain normal sexual
      function. The impact of androgens on lipid metabolism and prostate physiology
      must be clarified. Lack of funding is the greatest barrier to further research
      and the development of a hormonal contraceptive for men.

PMID- 9520590
TI  - [Where will community medicine be in 20 years?].

PMID- 9520591
TI  - [The essence of community medicine].

PMID- 9520592
TI  - [Too good to be true--too bad for publishing].

PMID- 9520593
TI  - [Mother, child and health--unethical control].

PMID- 9520594
TI  - Gene conversion in mitotically dividing cells: a view from Drosophila.

PMID- 9520595
TI  - Genetic redundancy in vertebrates: polyploidy and persistence of genes encoding
      multidomain proteins.

PMID- 9520596
TI  - Genetics in profile. IBC's Conference on Genetic Profiling and Diagnostics, San
      Diego, CA, USA, 29-30 October, 1997.

PMID- 9520597
TI  - 'Small genomics' on a large scale. E. coli and small genomes, American Society
      for Microbiology, Snowbird, UT, USA, 12-15 October 1997.

PMID- 9520598
TI  - The evolution of 'bricolage'.
AB  - The past ten years of developmental genetics have revealed that most of our genes
      are shared by other species throughout the animal kingdom. Consequently, animal
      diversity might largely rely on the differential use of the same components,
      either at the individual level through divergent functional recruitment, or at a
      more integrated level, through their participation in various genetic networks.
      Here, we argue that this inevitably leads to an increase in the interdependency
      between functions that, in turn, influences the degree to which novel variations
      can be tolerated. In this 'transitionist' scheme, evolution is neither inherently
      gradualist nor punctuated but, instead, progresses from one extreme to the other,
      together with the increased complexity of organisms.

PMID- 9520599
TI  - The DNA revolution in population genetics.
AB  - Unprecedental clarity has come to our understanding of genetic variation by the
      analysis of DNA sequences. It is not surprising that the new DNA technologies are
      leading to a resurgence of interest in population genetics. In this review, I
      discuss recent progress and future directions towards reconstructing the history
      of human populations. There is increasing consensus on a recent 'Out of Africa'
      origin of modern humans, which explains why the greatest fraction of genetic
      diversity is found within populations, rather than between them. The comparison
      of Y chromosome and mitochondrial DNA data shows remarkable sex differences in
      geographic variation. The analysis of Neanderthal DNA has been a major
      breakthrough in the study of fossil DNA. Among major hopes for the future are
      application to polygenic diseases.

PMID- 9520600
TI  - The cyclin family of budding yeast: abundant use of a good idea.
AB  - Cyclins are highly conserved proteins that activate cyclin-dependent kinases
      (CDKs) to regulate the cell cycle, transcription and other cellular processes.
      The completion of the genome sequence of the budding yeast Saccharomyces
      cerevisiae allows an appraisal of the functions of the entire complement of
      cyclins in a eukaryotic organism. The cyclin family of budding yeast is reviewed
      from a functional perspective with an emphasis on what genetic and biochemical
      experiments have revealed about cyclin-CDK substrates.

PMID- 9520601
TI  - Controlling your losses: conditional gene silencing in mammals.
AB  - Methods are now widely used in mice, and to a lesser extent in mammalian-cell
      culture, for the constitutive silencing of target genes in order to assess their
      function. For a variety of reasons, not least because many genes are essential
      for viability, it is important that these methods can be adapted to allow the
      controlled silencing of target genes. Reviewed here are the ways in which gene
      silencing methods can be combined with a growing number of genetic control
      systems to generate cell lines or mice that are, in effect, conditional mutants.
      These approaches are still being developed and promise to open up key areas of
      cell and animal biology to genetic analysis.

PMID- 9520602
TI  - How to get the best of dbEST.

PMID- 9520603
TI  - It's a knockout!

PMID- 9520604
TI  - The effect of alternative work arrangements on women's well-being: a demand
      control model.
AB  - The growth of women's participation in the labor force and evidence of the
      conflict they experience between job and family demands have spurred many
      employers to introduce alternative work arrangements such as flextime, job
      sharing, and telecommuting. Drawing on data gained from a sample of women (N =
      998) in two large Canadian organizations, this study evaluates two mediational
      models of the impact of alternative work arrangements on women's stress and
      family role competence. Specifically, it tests and finds support for the
      hypotheses that (a) work arrangements involving scheduling flexibility
      (telecommuting and flextime) promote these aspects of women's well-being by
      increasing their perceived control over their time, and (b) arrangements
      involving reduced hours of employment (part-time employment and job sharing)
      promote well-being by reducing perceived job overload. Discussion of these
      findings centers on their implications for employed women, their employers, and
      future research.

PMID- 9520605
TI  - A home-based behavioral intervention to promote walking in sedentary ethnic
      minority women: project WALK.
AB  - A home-based telephone and mail intervention was evaluated for its effectiveness
      in promoting walking in a sample of sedentary, ethnic minority women. One hundred
      twenty-five women (ages 23-54) were randomly assigned to behavioral or brief
      educational interventions. Women in the 8-week behavioral condition received
      behavior change materials through the mail and 6 structured telephone counseling
      sessions. Educational condition participants received a single 5-min telephone
      call and educational information. Both groups reported significantly increased
      walking at a 2-month posttest (M change = 86 and 81 min per week for behavioral
      and educational groups, respectively) and 5-month follow-up (M change = 40 and 52
      min per week). A 30-month follow-up of 50 participants indicated both groups
      continued to report more walking than at baseline. The behavioral intervention
      was not superior to the educational condition at any assessment point. The
      findings may be explained as (a) both interventions were equally effective, so
      extensive telephone counseling is unnecessary; (b) changes over time reflected
      secular trends; or (c) increases in self-reported walking may be due to socially
      desirable reporting. Other strategies need to be evaluated for promoting walking
      that are tailored to the needs of ethnic minority women.

PMID- 9520606
TI  - The long-term effects of battering on women's health.
AB  - We examined the effects of intimate violence on the physical and psychological
      health of women over time. Changes in levels of physical and psychological abuse,
      injuries, physical health symptoms, anxiety, and depression were assessed three
      times: immediately after exit from a domestic violence program and at 81/2- and
      141/2-month follow-ups. Analyses showed a significant decline in abuse, physical
      health symptoms, anxiety, and depression over time. Longitudinal structural
      equation modeling demonstrated that ongoing abuse was significantly related to
      increased physical and psychological health problems from one time period to the
      next, even when prior levels of physical and psychological health were
      controlled. Within each time interval, the effects of abuse on physical symptoms
      appeared to be mediated through anxiety and depression; although this
      relationship was replicated at several time points, the mediation was not
      verified across time, probably because measurement intervals were too long to
      reflect the underlying causal sequence. Although injuries were the direct result
      of abuse, injuries showed no significant effect on physical symptoms, anxiety, or
      depression. Implications for intervention and future research are discussed.

PMID- 9520607
TI  - Provision of mental health services in women's health centers.
AB  - Women's health centers are often associated with a comprehensive model of health
      care that treats the "whole woman." Using data from a nationwide study of 467
      women's health centers, we explored how the ideal of comprehensive care was
      implemented with respect to mental health services. Specifically, we examined the
      rates of screening and treatment for a subset of mental health and behavioral and
      social problems in women's health centers and the structural, staffing,
      philosophical, and patient factors associated with the provision of services.
      Across 12 services, the overall rates of provision ranged from 7.7% for screening
      for dementing disorders to 27.6% for smoking cessation counseling and treatment.
      In a series of logistic regressions, center type (primary care) and having a
      mental health staff person were consistently associated with service provision;
      other important variables were having a high percentage of women using the center
      as their usual source of care and having a belief in women-centered care.
      Findings indicate that the majority of women using women's health centers do not
      receive services in a comprehensive care environment that includes key mental
      health services.

PMID- 9520608
TI  - Naive beliefs about breast cancer risk.
AB  - We examined the beliefs women have about their risk of breast cancer.
      Participants were 86 women, ages 18 to 90, with and without a family history of
      breast cancer. They were interviewed individually about their risk and their
      beliefs about risk factors for breast cancer. The results showed that
      participants form their risk estimates primarily from the absence or presence of
      a family history of breast cancer. When asked to compare their risk with the risk
      of others, only participants without a family history viewed their chances of
      getting breast cancer as lower than the chances of others. On an absolute risk
      measure, all participants overestimated their risk. Different risk measures can
      lead to different conclusions about how women perceive their risk. In addition,
      the nearly exclusive focus of women on family history may create difficulties for
      genetic counselors providing information about breast cancer risk.

PMID- 9520609
TI  - [Catheterization in congenital heart defects and vascular malformations].

PMID- 9520610
TI  - [Mortality in coronary thrombosis].

PMID- 9520611
TI  - [Trauma centers].

PMID- 9520612
TI  - [Arrhythmogenic right ventricular cardiomyopathy].
AB  - Arrhythmogenic right ventricular dysplasia is a rare cardiomyopathy, but a
      frequent cause of ventricular tachyarrhythmia and sudden cardiac death among
      young otherwise healthy individuals. This article contains a review of the
      current knowledge on epidemiology, diagnosis, symptoms and signs as well as
      theories on etiology and pathogenesis, prognosis and treatment. The aim is to
      draw attention to the disease as a cause of syncope, ventricular tachycardia and
      sudden cardiac death.

PMID- 9520613
TI  - [Teratogenic effects of ACE-inhibitors and angiotensin II receptor antagonists].
AB  - Since the introduction of angiotensin converting enzyme-inhibitors (ACE
      inhibitors) in the 1980's, more than 50 cases of foetotoxic effects ascribed to
      intrauterine exposure to inhibitors have been published. Among the most commonly
      reported effects are: Hypotension, renal dysplasia, anuria/oliguria,
      oligohydramios, intrauterine growth retardation, pulmonary hypoplasia, unclosed
      ductus arteriosus, incomplete ossification of the skull, intrauterine og neonatal
      death. Recent animal studies have confirmed that intrauterine or neonatal
      exposure to ACE-inhibitors or the AT1-receptor antagonist losartan can cause
      death and serious, irreversible organ damage. These effects are similar to the
      complications previously reported in humans. Animal studies suggest that the
      foetotoxic actions are most common after exposure during the last trimester.
      However, due to the severity of these complications, the use of ACE-inhibitors
      and AT1-receptor antagonists should be avoided throughout pregnancy and in women
      who are breast feeding.

PMID- 9520614
TI  - [Percutaneous transluminal embolization of pulmonary arteriovenous
      malformations].
AB  - A series of nine patients with pulmonary arteriovenous malformations (PAVM)
      treated with embolotherapy at Odense University Hospital is presented. In all
      patients the arterial oxygen tension increased after embolisation. PAVM causes
      right-to-left shunting, which may result in severe hypoxaemia, and, due to lack
      of the normal filter function of the lung, paradoxical embolism. Women are
      particularly at risk during pregnancy. Among patients with Hereditary
      Haemorrhagic Telangiectasia 15-33% also have PAVM. Embolotherapy is a safe and
      efficacious treatment for occlusion of PAVM. Since serious complications to the
      disease can be prevented, all HHT patients should be offered screening for PAVM,
      and treated if required.

PMID- 9520615
TI  - [Occupational and chronic inflammatory bowel disease in Denmark].
AB  - It has been suggested that some occupational groups have a high risk of
      contracting chronic inflammatory bowel diseases. A cohort, comprising 2,273,872
      male and female Danes aged 20-59 on 1 January 1981, and a cohort similarly
      defined as of 1 January 1986 were followed up for hospitalizations due to chronic
      inflammatory bowel disease until 31. December 1990. From 1981 to 1990, 6296 first
      time admissions occurred. Among 15 groups previously found to be at high or low
      risk only female office staff and health personnel had statistically
      significantly increased standardized hospitalization ratios. Occupations with non
      daytime work did not have an increased risk. Occupations with predominantly
      sedentary work had a standardized hospitalization ratio of 125 (95% confidence
      interval 116.9-133.1) compared to occupations without sedentary work. Self
      employed had low hospitalization rates, while 'other salaried staff' and "not
      economically active" had high rates.

PMID- 9520616
TI  - [Substrate metabolism in untreated and treated thyrotoxicosis].
AB  - Accelerated metabolism is a hallmark of thyrotoxicosis, but the underlying
      biochemical mechanisms are incompletely understood. In order to elucidate these
      metabolic events further, we studied 12 patients with newly diagnosed diffuse (10
      patients) or nodular (two patients) toxic goitre (ten women, two men; age 42.8 +/
      3.2 yr; BMI: 21.6 +/- 0.7 kg/m2) before ("TOX") and after ("TRE") 11.2 +/- 1.0
      weeks treatment with methimazole and compared these patients to a control group
      ("CTR") of 11 subjects (nine women, two men; age 40.5 +/- 3.9 yr; BMI 22.5 +/-
      1.0 kg/m2). All were studied for three hours in the basal state, using indirect
      calorimetry, isotope dilution for measurement of glucose turnover and the forearm
      technique for assessment of muscle metabolism. Prior to treatment patients with
      thyrotoxicosis were characterized by: Increased (p < 0.05) levels of T3 (3.75 +/-
      0.23 [TOX], 1.89 +/- 0.08 [TRE] and 1.75 +/- 0.11 [CTR] nmol/l), resting energy
      expenditure (130.5 +/- 3.5 [TOX], 107.7 +/- 2.7 [TRE] and 106.3 +/- 3.1 [CTR]
      percent of predicted), protein oxidation (0.67 +/- 0.03 [TOX], 0.54 +/- 0.06
      [TRE] and 0.46 +/- 0.05 [CTR] mg/kg/min), lipid oxidation (1.34 +/- 0.08 [TOX],
      1.00 +/- 0.06 [TRE] and 1.02 +/- 0.04 [CTR] mg/kg/min), endogenous glucose
      production (2.51 +/- 0.13 [TOX], 1.86 +/- 0.12 [TRE] and 1.85 +/- 0.12 [CTR]
      mg/kg/min), non-oxidative glucose turnover (1.28 +/- 0.16 [TOX], 0.75 +/- 0.18
      [TRE] and 0.71 +/- 0.11 [CTR] mg/kg/min) and a 50% increase in total forearm
      blood flow. Glucose oxidation (1.23 +/- 0.09 [TOX], 1.13 +/- 0.10 [TRE] and 1.13
      +/- 0.09 [CTR] mg/kg/min), exchange of substrates in the muscles of the forearm
      and circulating levels of insulin, C-peptide, growth hormone or glucagon were not
      influenced by hyperthyroidism. Propranolol (20 mg thrice daily) given to seven of
      the patients for two days did not affect circulating levels of thyroid hormones,
      energy expenditure or glucose turnover rates. These results suggest that all
      major fuel sources contribute to the hypermetabolism of thyrotoxicosis and that
      augmented non-oxidative glucose metabolism may further aggravate the condition.
      All abnormalities recede with medical treatment of the disease.

PMID- 9520617
TI  - [Malignant melanoma in the small intestine].
AB  - A case story of malignant melanoma is presented. The tumour was localised to the
      jejunum. The symptoms, diagnosis and treatment are described and the pathogenesis
      is discussed.

PMID- 9520618
TI  - [Magnetic resonance imaging in musculoskeletal tuberculosis].
AB  - The incidence of tuberculosis in Denmark has increased over the last years. Two
      cases of primary osteoarticular tuberculosis are described: tuberculous ostitis
      of the scapula and surrounding soft tissue, and tuberculosis of the elbow. We
      have emphasized the appearance on magnetic resonance imaging (MRI), as the role
      of this modality has only been sporadically described for osteoarticular
      tuberculosis in areas other than the vertebral column. The cases show that MRI
      can contribute to a more precise determination of the extent of osteoarticular
      tuberculosis and its soft tissue involvement.

PMID- 9520619
TI  - [Is cardiovascular disease a contraindication for nicotine substitution?].

PMID- 9520620
TI  - [Trauma treatment in Denmark].

PMID- 9520621
TI  - [Attitude of parents to treatment of extremely premature infants].

PMID- 9520622
TI  - [ACE-inhibitors in angina pectoris].

PMID- 9520623
TI  - [Acute treatment of gout].

PMID- 9520624
TI  - Video based lifting technique coding system.
AB  - Despite automation and improved working conditions, many materials in industry
      are still handled manually. Among the basic activities involved in manual
      materials handling, lifting is the one most frequently associated with low-back
      pain (LBP). Biomechanical analysis techniques have been used to better understand
      the risk factors associated with manual handling, but because these techniques
      require specialized equipment, highly trained personnel, and interfere with
      normal business operations, they are limited in their usefulness. A video based
      lifting technique analysis system (the VidLiTeCTM System) is presented that
      provides for quantifiable non-invasive biomechanical analysis of the dynamic
      features of lifting with high inter-coder reliability and low sensitivity to
      absolute errors. Analysis of results from a laboratory experiment and from field
      collected videotape are described that support the reliability, sensitivity, and
      accuracy claims of the VidLiTeCTM System. The VidLiTeCTM System allows
      technicians with minimal training and low-tech equipment (a camcorder) to collect
      large sets of lifting data without interfering with normal business operations. A
      reasonably accurate estimate of the peak compressive force on the L5/S1 joint can
      be made from the data collected. Such a system can be used to collect quantified
      data on lifting techniques that can be related to LBP reporting.

PMID- 9520626
TI  - Does display configuration affect information sampling performance?
AB  - This investigation sought to determine the influence of a visual display's
      spatial configuration on participant's ability to sample linguistic information.
      Line drawings circumscribed 36 areas shaped like squares, rectangles, 'T', 'L'
      and '+', among others. Each such 'shape' was presented for 1000 ms, followed by a
      12-letter matrix presented for 50 ms. Participants then reported the letters that
      would have been inside the boundary contour if it were superimposed on the letter
      matrix. The results indicated that single, spatially contiguous areas could be
      monitored better than separate areas; the recall of simple configurations seemed
      better than that of more complex ones, while outlying positions tended to be
      ignored. The data were thus viewed as compatible with recent theories of
      perceptual organization in displays, such as the notion of 'common region' and
      the proximity compatibility principle. Informational complexity (IC) proved
      somewhat better than figural compactness (FC) in accounting for the data in terms
      of information theory. The findings may help to specify the optimal spatial
      configurations for visually displayed linguistic information in a variety of
      contexts, including head-up displays (HUDs).

PMID- 9520625
TI  - Gaze angle: a possible mechanism of visual stress in virtual reality headsets.
AB  - It is known that some Virtual Reality (VR) head-mounted displays (HMDs) can cause
      temporary deficits in binocular vision. On the other hand, the precise mechanism
      by which visual stress occurs is unclear. This paper is concerned with a
      potential source of visual stress that has not been previously considered with
      regard to VR systems: inappropriate vertical gaze angle. As vertical gaze angle
      is raised or lowered the 'effort' required of the binocular system also changes.
      The extent to which changes in vertical gaze angle alter the demands placed upon
      the vergence eye movement system was explored. The results suggested that visual
      stress may depend, in part, on vertical gaze angle. The proximity of the display
      screens within an HMD means that a VR headset should be in the correct vertical
      location for any individual user. This factor may explain some previous empirical
      results and has important implications for headset design. Fortuitously, a
      reasonably simple solution exists.

PMID- 9520627
TI  - Postural motor programming in paraplegic patients during rehabilitation.
AB  - One of the basic aims in the rehabilitation of thoracic spinal cord injured (SCI)
      patients concerns the regaining of sitting posture control. This implies the
      development of new postural strategies requiring the adjustment of motor
      programming processes. The aim of this study was to investigate the time course
      of postural reorganization during active, clinical rehabilitation of thoracic SCI
      patients with different SCI levels. Thus changes in motor programming in sitting
      balance control were investigated in two groups of complete low or high thoracic
      SCI patients. At several stages during the rehabilitation process an experiment
      was held in which sitting posture was perturbed systematically using submaximal
      reaching movements over four reaching distances. This bimanual reaching task was
      presented as a visual precue choice reaction time (RT) task in which reaching
      distance (i.e. grade of postural perturbation) was precued. Results indicated
      that in both high and low thoracic SCI patients RTs in movements involving
      postural perturbation became shorter during the course of the rehabilitation
      period. However, low thoracic SCI patients were generally slower in the
      programming of balance perturbing movements than high thoracic SCI patients, a
      phenomenon that did not change over time. Furthermore, initial differences in RTs
      as a function of grade of postural perturbation disappeared in both groups in the
      course of the rehabilitation phase. Precue benefit, equally large for both
      groups, did not change as a function of rehabilitation time. It is concluded that
      the observed phenomena signify the gradual development of new central postural
      control processes in both SCI groups during rehabilitation. Low thoracic SCI
      patients, having more residual sensorimotor functions, seem to adopt more complex
      strategies in maintaining and restoring sitting balance that take longer to
      specify and to programme. High thoracic SCI patients seem to rely on simpler
      strategies using more passive postural support.

PMID- 9520628
TI  - Research on pelvic angle variation when using a pelvic support.
AB  - A pelvic support consisting of a forward sloping wedge of foam has been tested as
      an addition to conventional office seating for VDT work. In experiment 1 a
      questionnaire investigation was carried out on the impressions of 10 male and 10
      female subjects who sat using pelvic supports. A general result from the
      questionnaire was that the waist and pelvis were felt to be stable and the
      evaluation was more positive with the support than without. In experiment 2,
      pelvis and chest inclinations were measured during sitting with and without the
      pelvic support. Over a long work period, significant differences were not
      observed. In both cases, subjects were able to move freely and there were no
      significant changes in posture. In experiment 3, pelvis and chest inclinations
      were measured in conditions of no pelvic support and with supports of 10, 20 and
      30 degrees. The experiment demonstrated that a support angle of 10 degrees was
      stable and comfortable. In this research, it was found that the change of
      inclination of the pelvis can be measured continuously using an angle of
      inclination sensor. Imposing a forward slope of 4 to 10 degrees on the seat pan
      surface using the pelvic support had a positive effect, while angles of 20 and 30
      degrees had a negative effect.

PMID- 9520629
TI  - Effects of endurance training and heat acclimation on psychological strain in
      exercising men wearing protective clothing.
AB  - Two experiments examined the influences of endurance training and heat
      acclimation on ratings of perceived exertion (RPE) and thermal discomfort (RTD)
      during exercise in the heat while wearing two types of clothing. In experiment 1,
      young men underwent 8 weeks of physical training [60-80% of maximal aerobic power
      (VO2max) for 30-45 min day-1, 3-4 days week-1 at 20-22 degrees C dry bulb (db)
      temperature] followed by 6 days of heat acclimation [45-55% VO2max for 60 min day
      1 at 40 degrees C db, 30% relative humidity (rh)] (n = 7) or corresponding
      periods of control observation followed by heat acclimation (n = 9). In
      experiment 2, young men were heat-acclimated for 6 or 12 days (n = 8 each).
      Before and after each treatment, subjects completed bouts of treadmill exercise
      (1.34 m s-1, 2% grade in experiment 1 and 0% grade in experiment 2) in a climatic
      chamber (40 degrees C db, 30% rh), wearing in turn normal light clothing
      (continuous exercise at 37-45% VO2max for a tolerated exposure of 116-120 min in
      experiment 1 and at 31-34% VO2max for 146-150 min in experiment 2) or clothing
      protective against nuclear, biological, and chemical agents (continuous exercise
      at 42-51% VO2max for a tolerated exposure of 47-52 min in experiment 1 and
      intermittent exercise at 23% VO2max for 97-120 min in experiment 2). In
      experiment 1, when wearing normal clothing, endurance training and/or heat
      acclimation significantly decreased RPE and/or RTD at a fixed power output. There
      were concomitant reductions in relative work intensity (% VO2max) [an unchanged
      oxygen consumption (VO2) but an increased VO2max, or a reduced VO2 with no change
      of VO2max], rectal temperature (Tre), mean skin temperature (Tsk), and/or heart
      rate (HR). When wearing protective clothing, in contrast, there were no
      significant changes in RPE or RTD. Although training and/or acclimation reduced
      %VO2max or Tre, any added sweat that was secreted did not evaporate through the
      protective clothing, thus increasing discomfort after training or acclimation.
      Tolerance times were unchanged in either normal or protective clothing. In
      experiment 2, when wearing normal clothing, heat acclimation significantly
      decreased RPE and RTD at a fixed power output, with concomitant reductions in
      Tre, Tsk, and HR; the response was greater after 12 than after 6 days of
      acclimation, significantly so for RPE and HR. When wearing protective clothing,
      the subjects exercised at a lower intensity for a longer duration than in the
      moderate exercise trial. Given this tactic, either 6 or 12 days of heat
      acclimation induces significant reductions RPE and/or RTD, accompanied by
      reductions in Tre, Tsk, and/or HR. Tolerance times in protective clothing were
      also increased by 11-15% after acclimation, despite some increase of sweat
      accumulation in the protective clothing. The results suggest that (1) neither
      endurance training nor heat acclimation reduce psychological strain when
      protective clothing is worn during vigorous exercise, because increased sweat
      accumulation adds to discomfort, and (2) in contrast to the experience during
      more vigorous exercise, heat acclimation is beneficial to the subject wearing
      protective clothing if the intensity of effort is kept to a level that allows
      permeation of sweat through the clothing. This condition is likely to be met in
      most modern industrial applications.

PMID- 9520630
TI  - In vivo treatment of bullfrog tadpoles with aldosterone potentiates ACh-receptor
      channels, but not amiloride-blockable Na+ channels in the skin.
AB  - Amiloride-blockable Na(+) channels participate in active Na(+) transport across
      adult, but not larval, bullfrog skin. Their development is induced in vitro by
      culturing the tadpole skin with aldosterone. When tadpoles were raised in
      aldosterone (5 x 10(-7) M) for 2 weeks, however, neither development of such
      channels nor localization of antigen A, a marker of adult-type epidermis, was
      seen, the skin still being of the larval type. In contrast, aldosterone treatment
      did potentiate (by a factor of two) the activity of the acetylcholine receptor
      (ACh-receptor) channel, a functional marker of larval-type skin. The short
      circuit current (SCC) across the skin, far from being inhibited by amiloride, was
      stimulated by both amiloride and ACh. The nystatin-stimulated SCC was about twice
      its control amplitude, suggesting that the aldosterone treatment also potentiated
      the activity of the Na(+) pump.

PMID- 9520633
TI  - Leech extracellular hemoglobin: two globin strains that are akin to vertebrate
      hemoglobin alpha and beta chains.
AB  - Leech (Whitmania edentula, Haemadipsa zeylanica var. japonica and Erpobdella
      lineata) extracellular hemoglobins are basically composed of three constituent
      subunits, a dimer (D1 and D2 chains) and two monomers (M1 and M2 chains). We
      isolated these four chains from respective species by a combination of reversed
      phase chromatography on a Resource RPC column and gel-filtration on a Superdex 75
      column. The apparent molecular masses of the four globin chains were estimated by
      SDS-PAGE analysis to be 13 kDa (M1), 16 kDa (M2; 19 kDa in its reduced form) and
      about 27 kDa for the dimer subunit (13 kDa for D1; 15 kDa for D2), regardless of
      the source. The amino (N)-terminal segments (21-30 residues) from twelve globin
      chains of the above three species were determined and aligned. It was found that
      the twelve sequences could be separated into two distinct globin groups A and B.
      This finding supports the original idea of "two globin strains in annelid
      hemoglobin", which was proposed without any evidence for leech hemoglobins.
      Comparing the sequences in the three classes of Annelida, Hirudinea, Oligochaeta
      and Polychaeta, we found two invariant amino acids, Cys and Trp, which are
      interposed by eleven amino acid residues. Furthermore, the globin chains
      belonging to strain A were readily discernible as they had three more invariants,
      Ser-13, Asp-16 and Trp-28, while the globin chains of strain B had two more
      invariants, Lys-12 and Arg-27. Consequently, we propose that each of the three
      classes of Annelida have two distinct groups of globin chains that are akin to
      vertebrate hemoglobin alpha and beta chains.

PMID- 9520632
TI  - Molecular cloning and expression of the KIF3A gene in the frog brain and testis.
AB  - KIF3A is a member of the kinesin superfamily proteins (KIFs), but its gene has
      been cloned only in mouse and sea urchin. We have cloned a homolog of KIF3A from
      the frog, Rana rugosa (rrKIF3A). The sequence encoded a 699 amino acid protein
      that shares 93% similarity with mouse KIF3A (mKIF3A) and 69% with sea urchin
      kinesin-related protein (SpKRP85). The putative ATP-binding domain was completely
      identical to that of mKIF3A and SpKRP85. The level of rrKIF3A mRNA appeared to be
      high in the brain and testis of adult frogs, but low in the heart, lung and
      kidney. The results suggest that the rrKIF3A gene is expressed in the brain and
      testis more than other tissues of adult frogs examined, and that KIF3A is widely
      distributed in eukaryotic organisms.

PMID- 9520634
TI  - Purification of EGIP-D-binding protein from the embryos of the sea urchin
      Anthocidaris crassispina.
AB  - Exogastrula-inducing peptides (EGIPs) are intrinsic factors that are present in
      eggs and embryos of the sea urchin Anthocidaris crassispina. They induce
      exogastrulation when added exogenously to the embryos. In the present study, we
      isolated an EGIP-D-binding protein (EBP) from a homogenate of mesenchyme
      blastulae. EBP had an apparent molecular weight of 33,000. The N-terminal amino
      acid sequence of EBP had a sequence homology to HLC-32 and bep4 identified in
      other sea urchin embryos. In addition to its ability of binding to EGIP-D, EBP
      also inhibited exogastrulation induced by EGIP-D. These results suggest that EBP
      plays an essential role in EGIP-D-induced exogastrulation.

PMID- 9520635
TI  - Stage-dependent distribution of calreticulin in oocytes of the frog, Rana rugosa.
AB  - We studied immunohistologically the distribution of a Ca2(+)-binding protein,
      calreticulin (CLT), at different stages of growing oocytes in the frog, Rana
      rugosa. Northern blot analysis showed that the CLT gene expression in gonads of
      metamorphosing tadpoles was low, but was extremely strong in the ovary, but not
      in the testis, of 2-month post-metamorphosis frogs, followed by decline to a
      lower level in adult frogs. On the contrary, the beta-actin gene expression did
      not increase in the same ovary. As for the distribution of CLT protein, a weak
      immunostaining was observed in indifferent gonads of tadpoles at stage I. The CLT
      distribution in oocytes from stage A to F was stage-dependent. In addition,
      Western blot analysis revealed that the CLT level was low in gonads of tadpoles
      at stage I, but increased at stage XVI. It still increased in the ovary of frogs
      2 months after metamorphosis, and then dropped to a lower level in adult frogs.
      The results indicate that CLT gene expression occurs in the early stage of
      growing oocytes, and that CLT is synthesized actively in oocytes in the ovary of
      frogs after metamorphosis. Based on these findings, the role of CLT is discussed.

PMID- 9520636
TI  - The protein tyrosine kinases of the sea urchin Anthocidaris crassispina.
AB  - In order to know the function of protein tyrosine kinases (PTKs) in the
      development of sea urchin embryos, we performed reverse transcription-polymerase
      chain reaction (RT-PCR) to obtain partial cDNA fragments for PTK genes using
      primers to highly conserved regions of the PTK family. A total of seven PTK
      sequences were identified, two of which represented receptor PTK (RTK1 and RTK2),
      and five of which were non-receptor PTKs (NRTK1-5). RTK1 was highly similar to
      FGF receptor and Ret kinase, while RTK2 showed features of the insulin receptor
      family. NRTK1 and 2 belonged to the Src family and could be involved in egg
      activation at fertilization. NRTK3 showed the features of the Btk family kinases,
      while NRTK4 seemed to be a member of the Syk/ZAP70 family. NRTK5 is the Csk-type
      kinase of the sea urchin, which is known to negatively regulate the Src family
      kinases. RTK1 was not detected in unfertilized eggs and was activated after
      blastula stage. All the other PTK genes were expressed both maternally in
      unfertilized eggs and zygotically after fertilization, though each gene showed
      distinct temporal patterns.

PMID- 9520637
TI  - Transcripts containing the sea urchin retroposon family 1 (SURF1) in embryos of
      the sea urchin Anthocidaris crassispina.
AB  - We isolated two cDNAs, termed D7 and C2 in the present study, from a cDNA library
      of the 16-cell embryo of the sea urchin Anthocidaris crassispina. The nucleotide
      sequence was determined completely for D7, and partially for C2. D7 does not have
      any significant open reading frames. Both D7 and C2 contain a common sequence
      that is 62% homologous to the sea urchin retroposon family 1 (SURF1). The SURF1
      is a short interspersed repetitive element identified from the sea urchin
      Strongylocentrotus purpuratus, and is reported to be transcribed by RNA
      polymerase III. The structural feature of D7 and C2, however, suggests that they
      may be transcribed by RNA polymerase II. RT-PCR analyses revealed that (1) both
      D7 and C2 transcripts exist as a maternal RNA in the egg, (2) they appear evenly
      distributed in the 16-cell embryo, and (3) C2 transcripts are present throughout
      the development up to the gastrula, while D7 transcripts decrease in amount after
      the early cleavage stage.

PMID- 9520638
TI  - Expression of actin genes in the arrow worm Paraspadella gotoi (Chaetognatha).
AB  - Arrow worms (the phylum Chaetognatha), one of the major marine planktonic
      animals, exhibit features characteristic to both deuterostomes and protostomes,
      and their ancestry therefore remains unknown. As the first step to elucidate the
      molecular bases of arrow worm phylogeny, physiology and embryology, we isolated
      cDNA clones for three different actin genes (PgAct1, PgAct2 and PgAct3) from the
      benthic species Paraspadella gotoi, and examined their expression patterns in
      adults and juveniles. The amino acid sequences of the three actins resembled each
      other, with identities ranging from 86% to 92%. However, the patterns of the
      spatial expression of the genes were independent. The PgAct1 gene might encode a
      cytoplasmic actin and was expressed in oogenic cells, spermatogenic cells, and
      cells in the ventral ganglion. The PgAct2 and PgAct3 genes encoded actins of
      divergent types. The former was expressed in well-developed muscle of the head
      (gnathic) region and trunk muscle cells, whereas the latter was expressed in
      muscle of the trunk and tail regions and oogenic cells. These results suggest
      that, similarly to other metazoans, the chaetognath contains multiple forms of
      actins, which are expressed in various manners in the adult and juvenile arrow
      worm.

PMID- 9520640
TI  - Apical ectodermal ridge-dependent expression of the chick 67 kDa laminin binding
      protein gene (cLbp) in developing limb bud.
AB  - Apical ectodermal ridge (AER)-mesoderm interaction is important for morphogenesis
      in the developing chick limb bud. Genes whose expression is dependent upon the
      presence of AER, are likely to play important roles in the AER-mesoderm
      interaction. We report here the gene expression pattern of the chick homolog of
      the 67 kDa laminin binding protein (LBP), which is a non-integrin laminin
      receptor whose function relates to cell attachment, spreading, and polarization.
      Northern analysis showed that a single 1.4 kb transcript exists in stage 20 limb
      buds and which is dramatically reduced 24 hr after removal of AER. In situ
      hybridization analysis revealed that the chick 67 kDa laminin binding protein
      gene (cLbp) was expressed in the mesodermal region overlapping the Msx1
      expressing domain and in the AER in early stage limb buds. Expression in the
      mesoderm was gradually restricted to the distal region underneath the AER as
      development proceeds. The expression in the limb mesoderm could be induced by
      local application of FGF-2 which could thus mimic the AER functions. These
      results indicated that the expression of cLbp depends on AER signals and that the
      67 kDa non-integrin receptor binding to laminin plays a role in the AER-mesoderm
      interaction.

PMID- 9520641
TI  - Cloning, sequence analysis, tissue-specific expression, and prohormone isolation
      of Eel atrial natriuretic peptide.
AB  - A complementary DNA (cDNA) encoding eel atrial natriuretic peptide (ANP)
      precursor was specifically amplified from eel atrial mRNAs by rapid-amplification
      polymerase chain reaction. The sequence analysis of the cDNA using multiple
      clones revealed that the preproANP consists of 140 amino acid residues carrying a
      signal sequence at its N-terminus and a mature ANP at its C-terminus. An
      additional glycine residue was attached to the C-terminus of previously isolated
      eel ANP. The glycine residue may be used for amidation of the C-terminus or
      removed after processing. The cleavage site of a signal peptide with 22 amino
      acid residues was confirmed by isolation of proANP protein from eel atria. The
      proANP sequence deduced from the cDNA was also confirmed for 71% of the isolated
      protein. Sequence comparison with other natriuretic peptides revealed that eel
      ANP is more similar to mammalian ANP than to B-type natriuretic peptide (BNP) at
      both amino acid and nucleotide sequence levels. The eel ANP gene was a single
      copy gene as shown by Southern blot analysis. Northern blot analysis showed that
      eel ANP mRNA is approximately 0.8 kb in size and exclusively detected in the
      atrium. Thus, eel ANP is a true atrial hormone judging from both the sequence and
      the site of production. However, reverse transcription-polymerase chain reaction
      detected ANP message in the brain, gill, cardiac ventricle, red body of swim
      bladder (rete mirabilis), intestine, head kidney (including interrenal and
      chromaffin tissues) and kidney. Most of these tissues are involved in ion and/or
      gas exchange in fishes.

PMID- 9520642
TI  - The role of the dental team in helping patients stop using tobacco.

PMID- 9520644
TI  - The patient said "no".

PMID- 9520645
TI  - Fabrication of an anterior In-Ceram bridge.
AB  - Although there have been only six years of clinical research and observation
      conducted on the In-Ceram bridge, this technique can be a viable treatment option
      of selected short-span anterior replacements. The esthetics as well as the
      biocompatibility results are excellent (Figure 9, Figure 10). In this case,
      something interesting happened. Previous to treatment the patient had a very
      difficult time smiling. Since the completion of this case, the patient smiles all
      the time because of the enhancement of her esthetics. She most definitely appears
      younger than her 81 years (Figure 11). She and her family are extremely pleased
      with the overall results.

PMID- 9520643
TI  - Backflow prevention: an update.

PMID- 9520646
TI  - Potential public health risks related to mercury/amalgam discharge from dental
      offices.
AB  - Mercury is a toxic and bioaccumulative metal. It exists in elemental, inorganic
      and organic forms. The use of mercury by the dental profession represents
      approximately 6 percent of the total annual domestic consumption and is estimated
      to contribute significantly to the discharge of mercury (14 percent in one study)
      to waste-water streams. Publicly owned treatment works (POTW) must obtain and
      comply with a National Pollutant Discharge Elimination System waste-water
      discharge permit. When minimal mercury discharge limits into surface waters are
      exceeded, an upstream search for contributors of mercury to the waste stream may
      result. Given the present sociopolitical environment, mercury discharge from
      dental offices will increasingly receive scrutiny. Strategies to minimize
      discharge of mercury/amalgam waste include engineering controls such as changes
      in the discharge process, changes in the composition of commercial products, and
      changes in control equipment. Governmental strategies include an outright ban,
      the setting of discharge standards, and educational efforts. Study of these
      strategies with evaluation of effectiveness is needed.

PMID- 9520647
TI  - Salt fluoridation: a report.

PMID- 9520648
TI  - Journey to the land of need.

PMID- 9520649
TI  - Payment arrangement guidelines: a "must" for your practice.

PMID- 9520650
TI  - How dentistry succeeds in preventing family violence.
AB  - Dentistry has a long history of dealing with one form of family violence: child
      maltreatment. However, a recent national survey shows that dentists are not
      living up to their legal and ethical obligations to report suspected child
      victims. Dentistry also needs to be equally concerned with adult victims of
      family violence--victims of spousal abuse and elder abuse and neglect. Successful
      child abuse prevention programs need to expand to cover all types of family
      violence. All health care professionals need education and awareness training to
      help develop the necessary attitudes to deal with victims of family violence.

PMID- 9520651
TI  - Restructuring your team to share the responsibilities of management.

PMID- 9520653
TI  - Patient records and medical history: tips to avoid liability.

PMID- 9520654
TI  - Your five-week plan to increase new patient flow.

PMID- 9520655
TI  - Implant-supported facial prostheses.
AB  - The application of the principles of osseointegration to the craniofacial
      skeleton can offer the patient with defects from trauma or ablative cancer
      surgery a functional and esthetic restoration, with minimal morbidity. Implant
      supported restorations offer a retrievable prosthesis with increased retention
      and support, by the use of tissue bars with clip retention, magnetic retentive
      mechanisms, or both. Implant-supported auricular, nasal, orbital, midfacial or
      combination prostheses are presently being provided for patients in hospitals,
      maxillofacial prosthetic training programs, and private practice settings in
      North America and elsewhere.

PMID- 9520656
TI  - New MDA survey: what patients think about dentists. Michigan Dental Association.

PMID- 9520657
TI  - Six effective ways to encourage patient loyalty.

PMID- 9520658
TI  - Michigan's successful dental bulk mercury collection program.

PMID- 9520659
TI  - Trends in caries experience in Michigan schoolchildren, 1986-1993.

PMID- 9520660
TI  - Putting the "manage" in managed care.

PMID- 9520661
TI  - Similarities between the development and treatment of plaque-induced peri
      implantitis and periodontitis.
AB  - Implants can be maintained in health with conscientious daily oral hygiene and
      regular professional maintenance. However, when inflammation develops, the peri
      implants tissues appear to be more susceptible to destruction. Peri-implant soft
      tissues seem to be more rapidly destroyed than dental tissues. This may be due to
      fiber direction, lack of blood supply, and fewer fibroblasts in the connective
      tissue, which are the microscopic differences as compared to the corresponding
      dental tissues. Therefore, long-term predictability with implants can only be
      assured with adequate oral hygiene and maintenance.

PMID- 9520662
TI  - Pre-operative radiographic evaluation of potential implant sites.

PMID- 9520663
TI  - The anterior single tooth implant restoration: a summary of current techniques.

PMID- 9520664
TI  - Spark erosion implant prosthetics in the management of an acquired maxillofacial
      defect.
AB  - The concept and use of spark erosion (EDM) prosthetics in implant prosthodontics
      has been described and demonstrated in its application to a patient suffering
      maxillofacial trauma. The advantages and disadvantages of this technology have
      been discussed for the edification of the restorative and surgical provider.

PMID- 9520665
TI  - The rationale for soft-tissue grafting and vestibuloplasty in association with
      endosseous implants: a literature review.
AB  - Significant soft-tissue complications have been reported around endosseous
      implant permucosal abutments. Peri-implants with associated bone loss can have a
      negative effect on the long-term prognosis of the implant reconstruction. The
      rationale for soft-tissue grafting and vestibuloplasty techniques is presented in
      the form of a literature review. The implant sulcular epithelium, permucosal
      seal, and the peri-implant connective tissues are discussed. The etiology of soft
      tissue complications as well as the significance of attached gingiva surrounding
      implant abutments are presented along with techniques for surgical intervention.

PMID- 9520666
TI  - A clinico-pathologic presentation. Ranula.

PMID- 9520667
TI  - Dentists play pivotal role in combating elder abuse.

PMID- 9520669
TI  - A clinico-pathologic presentation. Melanotic neuroectodermal tumor of infancy.

PMID- 9520668
TI  - Courage and grace in dentistry: the Noble, Freeman Connection.

PMID- 9520670
TI  - A clinico-pathologic presentation. Hereditary hypohidrotic ectodermal dysplasia,
      or HED.

PMID- 9520671
TI  - Guided bone regeneration in clinical practice: idealization of functional and
      esthetic endpoints.

PMID- 9520672
TI  - Wellness yields benefits for life.

PMID- 9520673
TI  - A clinico-pathologic presentation. Orofacial angiomatosis.

PMID- 9520675
TI  - Phantom tooth pain: differential diagnosis and treatment.

PMID- 9520674
TI  - Dentist practices and attitudes toward nutrition counseling.

PMID- 9520676
TI  - Assessing financial retirement assets.

PMID- 9520677
TI  - Oral cancer: current status and future hope.

PMID- 9520678
TI  - A systematic approach manages acute clinical pain.

PMID- 9520679
TI  - Is your front desk an efficient operations center?

PMID- 9520680
TI  - Harvard surgical units fight the Great War.

PMID- 9520681
TI  - A clinico-pathologic presentation. The diagnosis is traumatic bone cyst.

PMID- 9520683
TI  - Hypnosis provides therapeutic tool for patient management.

PMID- 9520682
TI  - Study examines preventive practices for older patients.

PMID- 9520684
TI  - Does laser therapy enhance wound healing?

PMID- 9520685
TI  - A distinguished dentist inspires his profession (Dr. Leonard Nathan).

PMID- 9520686
TI  - A clinico-pathologic presentation. The diagnosis is nicotine stomatitis.

PMID- 9520687
TI  - Is there a myofascial, temporomandibular disorder personality?
AB  - It is widely accepted that abnormal personality factors play an important role in
      the etiology and maintenance of myofascial-type temporomandibular disorder, or
      M/TMD. However, the foundation on which this belief rests is based largely on
      clinical lore, rather than on any evidence. The continued belief in the stress
      theory has important implications. Clinicians continue to be trained in unproven
      but traditionally sanctioned treatments. Such approaches not only may lead to
      problems of patient care, they may forge an unstable foundation for future
      research. Two theories are examined in this article: the psychosomatic and
      psychophysiological models. The findings show that both theories lack evidence,
      and further research is warranted because definitive studies are unavailable. The
      data from this study do not support the contention that M/TMD cases are
      characterized by a specific premorbid personality.

PMID- 9520688
TI  - A dual-diagnostic approach assesses TMD patients.
AB  - The understanding and treatment of patients with temporomandibular disorders, or
      TMDs, have been impeded by the lack of a consensually agreed-on classification
      system on which to make a differential diagnosis. A number of classification
      systems for these patients have been proposed. Some are based primarily on
      whether symptoms are myogenic or arthralgic--somatically based; some
      investigators have suggested that patients be differentiated on the basis of
      psychological characteristics. It has been suggested recently that patients be
      classified along two dimensions--physical and psychological. This article
      summarizes research describing the development of a psychosocial classification
      of TMD patients that can be used with the physical axis of the recently proposed
      research diagnostic criteria for classification of TMD patients. It also presents
      preliminary evidence supporting the clinical utility of the psychosocial
      classification.

PMID- 9520690
TI  - Toothaches that aren't really toothaches.

PMID- 9520689
TI  - Epidemiologic studies reveal trends in temporomandibular pain and dysfunction.
AB  - Recent epidemiologic investigations have provided novel perspectives concerning
      the type of patient in whom temporomandibular pain and dysfunction syndrome
      develops. Information regarding prevalence has challenged current concepts
      regarding signs and symptoms. Gender, age, ethnic, and socioeconomic data have
      provided insight into the risk factors, and have led to broader biopsychosocial
      investigations of the cause of this syndrome.

PMID- 9520692
TI  - Headaches that masquerade as dental pain.

PMID- 9520693
TI  - A clinico-pathologic presentation. The diagnosis is dentigerous cysts.

PMID- 9520691
TI  - Diagnosing and treating atypical odontalgia.

PMID- 9520694
TI  - Oh yes, I remember it well.

PMID- 9520696
TI  - Conversion of a fixed/removable partial denture into an immediate provisional
      complete denture.

PMID- 9520695
TI  - Traumatic injuries of the teeth sustained by battered women and children.

PMID- 9520697
TI  - A dental dilemma: is this child abuse? What are my responsibilities? What should
      I do?

PMID- 9520698
TI  - Non-bacterial rapidly progressive periodontitis--a case report.

PMID- 9520699
TI  - A clinical technique for temporization of teeth to receive porcelain laminate
      veneers.
AB  - Temporization of teeth prepared for porcelain laminate veneers is sometimes
      necessary to preserve occlusal relationships, prevent sensitivity or maintain
      esthetics. The literature describes several techniques which satisfy different
      requirements for temporization. A modified technique is presented that satisfies
      at once: occlusion, sensitivity and esthetic needs. Clinical time spent with the
      patient is minimized by fabricating a matrix on a diagnostic cast prior to the
      preparation/ impression appointment.

PMID- 9520700
TI  - Differential diagnosis of facial paralysis and Bell's palsy identifiable for
      dental surgeons--a review of the literature.

PMID- 9520701
TI  - Doctor ... what do you know about ALS?

PMID- 9520702
TI  - Sandblasting, silanating, and coatings: their effects on bond strength of metal
      brackets: an in vitro study.

PMID- 9520703
TI  - Atypical odontalgia--a nondental toothache.

PMID- 9520704
TI  - A history of dentistry in New Jersey, 1700-1870.

PMID- 9520705
TI  - Endodontic and periodontic diagnostic dilemmas.

PMID- 9520706
TI  - Selling your practice? Avoid potential problems.

PMID- 9520707
TI  - Increased performance using mouthguards--true or false?

PMID- 9520708
TI  - The botryoid odontogenic cyst: case report and twenty-five year literature
      review.
AB  - The botryoid odontogenic cyst (BOC) is a rare entity which has been sporadically
      reported in the literature since Weathers and Waldron coined the term in 1973.
      Approximately twenty-five such lesions have been described in the last twenty-one
      years. However, the histologic origin and nomenclature of this cyst have been
      quite controversial. Cysts with similar characteristics may have been seen even
      earlier than 1973, but were classified as other types of cysts of odontogenic or
      mesenchymal origin. The purpose of this article is to chronicle a case and its
      management, and to delineate several criteria to insure the proper diagnosis of
      the botryoid odontogenic cyst clinically, radiographically and histologically.

PMID- 9520709
TI  - Endodontic complications.

PMID- 9520710
TI  - I'd rather have a baby than root canal, or how to treat the fearful patient.
AB  - I have tried to enumerate the ways that can be used to communicate with the
      apprehensive patient in order to dispel the myths and allay the fears of root
      canal therapy. The categories discussed were communication, local anesthesia,
      nitrous oxide analgesia, pre-visit sedation and i.v. sedation. Some or all of
      these disciplines can be used depending on the situation.

PMID- 9520711
TI  - Clinical studies for evaluation of chemotherapeutic agents for control of plaque
      and gingivitis.

PMID- 9520712
TI  - Disability income insurance and the future.

PMID- 9520713
TI  - The real economics of PPOs.

PMID- 9520715
TI  - Non-surgical alternative in the treatment of skeletal Class III problems.
AB  - The dental profession is not static, but dynamic. New research findings, along
      with medical and technological advances, necessitate constant re-examination of
      treatment philosophies and techniques. What were acceptable treatment techniques
      in the past may not necessarily be the most effective and best techniques for our
      patients today. Currently, many practitioners feel that the only treatment for
      the correction of a skeletal Class III abnormality is via orthognathic surgery in
      older patients. In some cases it may be the only treatment option. But in most
      cases today, there are more conservative, non-surgical treatment alternatives in
      correcting Class III problems in younger aged children. In treating facial
      skeletal problems, it must be emphasized that the human face is a biological
      masterpiece of form and function. Its importance has been documented in arts and
      sciences since the beginning of modern civilization. It is important enough so
      that individuals who are blessed with attractive features are afforded greater
      opportunities in our society. Attractive faces are associated with intelligence,
      honesty and good work ethics. With the advent of orthognathic surgery, functional
      appliance, functional regulator, and myofunctional therapy, the dental profession
      has the capability of leveling out the playing field for many individuals in our
      society. It does so by being able to correct problems closely associated with the
      human psyche--the human face. The ability to change facial features brings
      tremendous prestige to our profession. Along with this prestige comes greater
      responsibility. Our ability to change facial features entails greater
      understanding of facial balance and harmony. Ricketts states that the face must
      conform to stringent proportions known as the "divine proportion" in order for it
      to be esthetically pleasing. Also, our ability to move facial-skeletal structures
      entails greater understanding of the biomechanics of the human face. Without this
      knowledge practitioners can cause iatrogenic problems, such as temporomandibular
      disorders. Conversely, correcting facial-skeletal abnormalities have been found
      to alleviate many medical problems, such as chronic headaches, neck-back-shoulder
      pain, respiratory disorders, auditory disorders, etc. As more and more
      information is gathered, it is becoming clear that the physical, emotional and
      psychological health of a human being is intimately related to craniomandibular
      anatomy. In fact, the jaw and dental structures (with the exception of the tooth
      enamel) is formed from the neural crest cells along with the endocrine system,
      while the central nervous system is formed from the neural tube. The entire
      nervous system, the endocrine system and the dental system are formed from common
      tissue origin. This can explain why many facial-skeletal corrections are often
      accompanied by alleviation of many medical and physiological problems. These are
      exciting times for our profession. However, if we wish to address the needs of
      our patients well into the next century, we must continue to seek greater and
      greater knowledge in the area of the craniomandibular anatomy relative to the
      rest of the human body. It has much to do with facial esthetics, physiologic and
      psychologic harmony, and TMJ health. This knowledge will enable our profession to
      have the power to change human lives in a very positive way. As doctors, there
      can be no greater personal and professional satisfaction than to realize that,
      through our professional intervention, we are able to offer our patients the
      possibility of achieving greater happiness and quality of life.

PMID- 9520716
TI  - Alphabetic potpourri--LLPs, LLCs, PAs, subchapters S & C--and your exposure to
      professional, tax and other liabilities. Limited liability partnership, limited
      liability company, professional associations.

PMID- 9520714
TI  - To say what is ours.

PMID- 9520717
TI  - New development in saving avulsed teeth.

PMID- 9520718
TI  - Intentional replantation: a case report and review of the literature.
AB  - Through a case report and a review of the literature, the indications and
      contraindications for intentional replantation are discussed. The current
      procedures and techniques for this seldom used modality are presented.

PMID- 9520719
TI  - What dentists need to know about CADM: complementary and alternative dentistry
      and medicine.
AB  - This article is written for dentists and paraprofessionals working with dentists,
      to provide a better understanding of the current and increasing acceptable
      modality of Complementary and Alternative Dentistry and Medicine. What dentists
      need to know about hypnosis, or mind-body imagery, a method and technique used in
      alternative dentistry, is explained in detail. Conscious behavior, also termed
      rational or normal consciousness, and subconscious behavior, also referred to as
      the altered state of consciousness, will be detailed. Once recognizing the role
      of this subconscious state, the main focus of this article is to describe what
      this state is, the characteristics that belong to this scientific practical
      phenomenon, and the key to how to induce this state, simply, readily and easily
      in eighty percent of dental patients.

PMID- 9520720
TI  - An office OSHA inspection--up close and personal.

PMID- 9520721
TI  - Happy fourth birthday OSHA bloodbornes! You mean you didn't get invited to the
      party either?

PMID- 9520722
TI  - Hazard communications standard: dentist-employers still must comply.

PMID- 9520723
TI  - Frequently asked OSHA questions.

PMID- 9520724
TI  - Elder abuse: how does it affect you and your patients?

PMID- 9520725
TI  - Latex hypersensitivity. When you are itching to work.

PMID- 9520726
TI  - The oral effects of AIDS. Seven most common lesions explored.

PMID- 9520727
TI  - Dental issues and techniques--1893.

PMID- 9520728
TI  - Informed consent and the dentist. Is our standard too high?

PMID- 9520729
TI  - Trigeminal neuropathies and the ever-changing standard of care.

PMID- 9520730
TI  - "But I want to go to sleep, and I don't want to feel anything"!

PMID- 9520731
TI  - When dental insurance disappears.

PMID- 9520732
TI  - Rx for hand pieces: preventive maintenance key to long life.

PMID- 9520733
TI  - Clinicopathologic correlation quiz: localized swelling of the gingiva. Pyogenic
      granuloma.

PMID- 9520734
TI  - Evaluation of microleakage in ceramic restorations.

PMID- 9520735
TI  - The University of Tennessee, College of Dentistry philosophy and technique for
      cleaning and shaping root canal systems.
AB  - The introduction of nickel titanium files has caused what the author believes to
      be revolutionary changes in the cleaning and shaping of root canal systems. New
      materials and file designs are constantly being evaluated and considered for
      introduction in the dental school curriculum. It is the purpose of this paper to
      review the techniques currently being taught and introduce some new ideas and
      techniques which are being evaluated for introduction into the curriculum in the
      future. Techniques using hand and rotary files will be presented in addition to a
      review of nickel titanium files.

PMID- 9520736
TI  - Assessing dental manpower needs in Tennessee.
AB  - Using a formula developed by the State of Kentucky and the best data available
      for the State of Tennessee, it is estimated that this state currently has a
      slight oversupply of dentists, but that by the turn of the century this will have
      become a shortage. There is no reason to doubt these estimates except that for
      confidence in them we will need state-specific data on the supply of dental
      manpower, the need for dental care, and the demand for dental care. Following the
      recommendations of the Institute of Medicine and others, the College of Dentistry
      has initiated the Dental Manpower Project to develop and maintain a database
      which will allow Tennessee to forecast and monitor trends in the supply of dental
      personnel and factors affecting need and demand. Hopefully, such an activity will
      help us avoid mistakes like those made 25 to 30 years ago which resulted in the
      education of too many dentists nationwide (and in this state) and an unfortunate
      breach between practitioners and dental education.

PMID- 9520737
TI  - Updating your medical history.

PMID- 9520738
TI  - Clinicopathologic correlation quiz: benign soft tissue swellings of the upper
      lip. Canalicular adenoma.

PMID- 9520739
TI  - Fluoridation status of Tennesseans, declining caries prevalence rates, increasing
      fluorosis, and a review of the appropriate use of fluoride products.

PMID- 9520740
TI  - Black-white difference in oral hygiene performance test scores. A preliminary
      finding.
AB  - This paper describes OHPT (Oral Hygiene Performance Test) which was used to
      measure race differences between African-American and European-American elderly
      65 years old and above in performance of daily oral hygiene activities. A total
      of 80 community-dwelling subjects of which 43 were African-American and 37
      European-American participated in the study which involved completion of a
      battery of functional status measurements including the OHPT. The instrument
      detected differences in performance as recorded by the length of time to complete
      each of the 17-items of OHPT. The instrument, the Oral Hygiene Performance Test,
      is a direct observation measure which objectively quantifies the ability to
      perform oral hygiene and thus reduces subjective evaluation.

PMID- 9520741
TI  - Initial placement and replacement of amalgam restorations: a retrospective
      review.
AB  - Restorative dentistry comprises a large amount of dental treatment. There is
      subjectivity among dentists concerning the reasons for initial placement and
      replacement of amalgam restorations. Different instructional methods and learned
      experiences while in private practice has much to do with this subjectivity even
      though, specific criteria have been established for standardization of initial
      placement and replacement of amalgam restorations. There are many reasons for the
      failure of amalgam restorations. Recurrent caries and material/tooth interface
      defects have been and are among the leading reasons for replacement. There are
      also differences in opinion among dentists concerning diagnosis of primary
      carious lesions.

PMID- 9520743
TI  - Dental patient substance abuse and addiction--impact upon the practice.

PMID- 9520742
TI  - Dental biomaterials in the 90s.

PMID- 9520744
TI  - The etiology and treatment of cervical erosion.
AB  - Erosion lesions are probably caused by a number of factors in combination.
      Symptomatic treatment is most indicated for lesions too shallow to restore. For
      the restoration of erosion, glass ionomer materials, because they eliminate the
      risk of secondary caries, remain the material of choice, although dentin-adhesive
      resins have been continuously improved. Recent light-cured glass ionomer
      restorative materials can be placed without most of the inconvenience inherent in
      earlier chemically cured materials, and like their chemically cured predecessors,
      can be veneered with composite resin to improve the esthetics of highly visible
      restorations.

PMID- 9520745
TI  - The number 12 crown excising forceps. Dentistry's most abusive instrument of the
      1880s.

PMID- 9520746
TI  - Liver transplantation: dentistry is an essential part of the team.
AB  - Liver transplantation has become a commonplace procedure, with more than 3,000
      livers being transplanted annually. Patient demand remains much greater than
      availability of donor organs, resulting in many deaths per year. Due to the
      nature of hepatic function, unique concern exists regarding susceptibility to
      infection and rejection during the post-transplant period, placing great
      importance on vigilant oral health maintenance. Patients are severely
      immunocompromised and must be well educated and treated pretransplant and for the
      rest of their post-transplant lives; however, even though patients are on waiting
      lists for matching donor livers for an adequate amount of time to provide
      definitive dental treatment, this is not a major priority on the protocols of
      some transplant centers. This paper addresses these concerns and illustrates a
      patient who presented shortly post-transplant with severe dental problems
      requiring immediate definitive treatment. As these patients may present in any
      office, general dentists should be aware of the unique concerns involving their
      assessment, education, treatment and maintenance.

PMID- 9520747
TI  - Reducing patient X-ray exposure by 75 percent for less than $75.

PMID- 9520748
TI  - The advanced education in general dentistry program at the College of Dentistry,
      University of Tennessee, Memphis.

PMID- 9520749
TI  - Microleakage of composite resin restorations with a 10 percent maleic acid
      etchant.
AB  - Microleakage of Class V composite resin restorations with margins all in enamel
      were compared in this in-vitro study using Scotchbond MultiPurpose Adhesive (SMP)
      (3M Corp.), and Scotchbond II (SB II) (3M Corp). Twenty extracted human molars
      were randomly separated into two groups: Group One, which used the SMP system and
      Group Two, which used the SB II system. Circular Class V preparations were cut
      1.8 mm deep and 3 mm in diameter using a #556 fissure bur. Cavosurface margins,
      all in enamel, were beveled. The enamel and dentin were treated following
      manufacturer's directions for each group, and a microfilled composite resin,
      Silux Plus (3M Corp), was applied in two hand-placed increments. All teeth were
      finished with Sof-Lex discs, stored in water for seven days, then thermocycled in
      a water bath for 100 cycles, alternating from 4 degrees C to 58 degrees C. The
      teeth were placed in a 5 percent solution of methylene blue, rinsed and then
      invested in resin. All teeth were sectioned vertically and horizontally and a
      ratio (percentage) of wall length to amount of leakage along each wall was
      established. The overall mean leakage of Group One was 15.27 percent and Group
      Two was 13.84 percent. Looking at individual walls, the mean occlusal wall
      leakage of Group One was 28.41 percent and Group Two was 12.45 percent. Mean
      gingival wall leakage of Group One was 15.96 percent and Group Two was 21.80
      percent. Comparing the two groups, using a student's t test, there was no
      significant difference between the overall mean leakage or between the gingival
      wall leakage (p > 0.05); however, there was a significant difference between the
      occlusal wall leakage (p < 0.05), with SMP exhibiting more leakage.

PMID- 9520750
TI  - Enamel microleakage of in-vivo Class V composite resin restorations using
      phosphoric acid versus maleic acid.

PMID- 9520751
TI  - Clinical esthetics of a light-cured and a chemically cured glass ionomer
      restorative material.

PMID- 9520752
TI  - Leukoedema: an epidemiological study in white and African Americans.
AB  - Leukoedema, a benign grayish-white lesion which characteristically involves the
      oral mucosa of humans, was once indicated as a probable precursor to leukoplakia.
      The author reports an incidence of fifty-three percent in a population of 13,000
      white and African Americans who reside in the Southeastern region of the United
      States. This longitudinal study revealed that the incidence of leukoedema per
      1,000 persons increased with age in both ethnic groups up to ages 40-49 and then
      declined systematically. There was no sex predilection. The occurrence of
      leukoedema was significantly greater in African Americans.

PMID- 9520754
TI  - Perimylolysis of the permanent dentition in an adolescent.
AB  - During a routine dental appointment at a dental school clinic, a fifteen-year-old
      black male patient was diagnosed with severe erosion of the dentition together
      with several carious lesions and a crowded dentition. During treatment of the
      carious lesions, severe erosion (perimylolysis) of the maxillary and mandibular
      teeth were observed, which at first alerted the attending clinician to a
      preliminary diagnosis of anorexia and/or bulimia. Because of the age, gender and
      social and medical history of the patient, these preliminary diagnoses were
      discounted, with a hypothesis of gastrointestinal disorder presented to the
      patient and his parents after consultation with oral medicine and oral pathology
      faculty. Saliva pH analysis, along with further research concluded that
      gastrointestinal reflux disease (GERD), surreptitious rumination, or a
      combination of both were possible diagnoses. Referral to a gastroenterologist for
      further examination was recommended, while a night-guard was fabricated for the
      patient to wear at night with fluoride gel. Root canal therapy together with
      prosthodontic care are often treatment options for patients suffering from
      gastrointestinal problems. This paper demonstrates how important routine dental
      examinations are, especially since dentists can often recognize systemic
      disorders whose symptoms first appear in the oral cavity.

PMID- 9520753
TI  - Clinicopathologic correlation quiz: unilocular periapical radiolucencies.
      Traumatic bone cyst.

PMID- 9520756
TI  - Latex allergies and adverse reactions: a review of the literature.
AB  - In the last few years, the allergenic potential of latex has been receiving
      greater attention. While latex allergies have been widely reported in the
      literature, the prevalence and severity have rapidly increased in the last few
      years. The role of rubber in the prevention of HIV infection has played a part in
      recognizing the allergenic potential, as with increased emphasis on infection
      control in the dental office has come an increase in complaints of adverse
      reactions to surgical gloves. A review of the literature reveals latex allergy
      problems to be not confined to gloves, but to articles of clothing, rubber dam
      material, and other latex-containing materials. Life-threatening cases have been
      reported. Little information in the literature concerns the extent of the problem
      among dental personnel. The dental professional may be faced with not only
      discomfort for the dental staff, but also compromising reactive possibilities in
      certain patients. There is a need for development of alternative protective
      products for the dental office, since elimination of barrier protection is not a
      viable alternative to infection control.

PMID- 9520755
TI  - Sealant leakage with and without isolation.

PMID- 9520757
TI  - Pit and fissure sealants: a review of rationale, effectiveness and utilization.

PMID- 9520758
TI  - Treatment of severe posterior interproximal caries with a combined glass ionomer
      amalgam restoration: a case report.

PMID- 9520759
TI  - The precision attachment removable partial denture.
AB  - This manuscript attempts to discuss intracoronal and extracoronal precision
      attachments. A clinical technique is presented which describes the use of
      intracoronal precision attachments to retain maxillary and mandibular removable
      partial dentures. Laboratory techniques are also described in this procedure.

PMID- 9520760
TI  - Pediatric conscious sedation: don't get caught sleeping!

PMID- 9520761
TI  - Preventive resin restorations vs. amalgam restorations: a three-year clinical
      study.
AB  - A three-year clinical study was completed at the College of Dentistry comparing
      the overall performance of Class I amalgam restorations with preventive resin
      restorations (PRRs). Seventy-four PRRs and fifty-two amalgam restorations were
      placed in the posterior teeth of thirty-eight patients. The PRR was composed of
      two materials: P-50 (3M Corp.), a heavily filled composite resin, and White
      Sealant (3M Corp.), a light-cured sealant. Fast-set Dispersalloy (Johnson and
      Johnson Corp.) was used for the amalgam restorations. The restorations were
      evaluated at six months, one year, two years and three years. The USPHS/Ryge
      system was used to evaluate anatomic form, marginal adaptation, marginal
      discoloration and recurrent caries of both type restorations. A restoration was
      considered a failure if any part of the restoration was replaced due to secondary
      caries. There were two failures of PRRs at six months, and four failures at one
      year. Failures were due to non retention of the sealant of the PRR and possibly
      related to operator error. The failures were easily repaired and removed from the
      study. No PRR failed at the two or three year evaluations. No amalgam restoration
      failed within the three year period.

PMID- 9520762
TI  - Update on HIV chemoprophylaxis following exposure.

PMID- 9520764
TI  - The role Tennessee's dentists must play in preventing child abuse and neglect.
AB  - Dentistry must become more aware of its moral, legal and ethical responsibilities
      in recognizing and reporting child abuse and neglect. All dental professionals
      must be aware of the seriousness of the problems of child maltreatment, and
      understand that children do not just get hurt in abuse and neglect, they often
      die as a direct result of their maltreatment. Unfortunately, as was pointed out
      by Warnick, victims of child abuse and neglect fall into only two categories-
      those who lived through it and those who did not.

PMID- 9520763
TI  - Compound odontoma associated with an impacted permanent central incisor.
AB  - In this case report, an eleven-year-old female presented to a rural dental clinic
      for routine dental examination. Upon evaluation of the dentition, the attending
      dentist discovered an over-retained primary tooth. Radiographically, a compound
      odontoma was present, gingival to an unerupted permanent maxillary left central
      incisor (number nine) and apical to the erupted primary central incisor (F). The
      odontoma and its overlying primary tooth were removed by an oral surgeon. The
      extraction site has healed uneventfully and an Orthodontic treatment plan was
      formulated. The etiology of odontomas is unknown but thought to be caused by
      trauma, infection, inheritance and/or genetic mutation. These lesions are usually
      found in the second decade of life and are more common in male patients.
      Treatment consists of complete enucleation and curettage of the odontoma site.

PMID- 9520766
TI  - Guaranteeing patient satisfaction.
AB  - Dental practice is about people and service. As the competition for patients
      increases, the successful practices will be the ones that focus increasingly on
      communication, relationship building and customer service. Quality care will be
      demonstrated through focusing on the total clinical and psychological aspects of
      patient satisfaction--and not just on technical parameters. Any practice can
      convert to a high level patient relations office if the commitment is truly
      there. These will be the leading practices of tomorrow.

PMID- 9520765
TI  - Avoiding the four mistakes that produce poor employee performance.

PMID- 9520767
TI  - Two-year clinical evaluation of preventive resin restorations.
AB  - A three-year clinical study is being conducted at the University of Tennessee,
      Memphis, college of Dentistry, comparing occlusal wear of Class I amalgam
      restorations with preventive resin restorations. This paper will concentrate on
      the two-year results of the preventive resin restoration with regards to
      placement technique, wear as evaluated by the USPHS system, marginal adaptation,
      recurrent caries, marginal discoloration, and address problems encountered.

PMID- 9520768
TI  - The use of lingual composite rests: a five-year update.

PMID- 9520769
TI  - The third and second divisions of the trigeminal nerve: dental considerations.

PMID- 9520771
TI  - Clinicopathologic correlation quiz: inter-radicular radiolucencies. Lateral
      periodontal cyst.

PMID- 9520770
TI  - Tobacco use and dental disease.
AB  - The previously cited Indiana University School of Dentistry teaching monograph,
      "The Impact of Tobacco Use and Cessation on Nonmalignant and Precancerous Oral
      and Dental Diseases and Conditions," reviewed over 800 articles and concluded
      that tobacco use is strongly associated with many dental and oral mucosal
      diseases, and may contribute to others. Our study of a relatively small sample of
      200 patients, of whom 33 percent were tobacco users, found statistically
      significant data correlating tobacco use with a higher Decayed, Missing and
      Filled Index (a measurement of caries and tooth loss experience of patients) and
      relating periodontal bone loss to smokeless tobacco use. And, while this
      investigation did not find a statistically significant correlation between
      smoking and periodontitis severity, there was a data trend in that direction.
      Conclusions about tooth loss in the Indiana monograph were limited to smokers;
      however, there was an association of ST use with gingival recession, which can
      become quite severe in the area in which the smokeless tobacco is placed. It
      might be theorized that the significantly larger number of missing teeth among ST
      users in our study is associated with the generally poor oral hygiene and less
      sophisticated outlook on health care that tobacco users often display. Indeed, of
      the 65 denture wearers in our study, 7.7 percent were ST users and 40.0 percent
      were tobacco users of some type. In view of the large amount of data in the
      scientific literature associating tobacco with dental diseases as summarized by
      the Indiana monograph, and the position of several groups such as the American
      Cancer Society that tobacco is one of the risk factors most associated with
      intraoral cancer, it would appear that dentists have a vested professional
      interest in promoting tobacco use cessation among their patients. Dentists should
      take every reasonable opportunity to persuade patients to discontinue the tobacco
      habit, thus preventing life-threatening malignancies as well as dental diseases.

PMID- 9520772
TI  - Patient satisfaction: the competitive advantage.

PMID- 9520773
TI  - Compressive properties of restorative cements.

PMID- 9520775
TI  - Posterior tooth replacement with a full crown and acid-etched wing as retainers.
AB  - With the advent of stronger adhesive materials and preparations that increase
      retention and lateral stability, acid-etched retainers provide an alternative
      approach to fixed bridges. Preparations for acid-etched retainers are more
      conservative, but may be more difficult to accomplish. Factors that must be
      considered to ensure successful cases include proper case selection, attention to
      preparation techniques, impression techniques, moisture control and cementation
      techniques.

PMID- 9520774
TI  - Update in systemic fluoride therapy.
AB  - The dental literature abounds with articles demonstrating drastic reductions in
      dental caries activity as a result of fluoride therapy. Recently, there has been
      concern over the number of fluorosis cases being seen. The prudent dental
      practitioner will utilize only approved products for systemic fluoride therapy,
      be aware of other possible sources of fluoride, and known the patient's fluoride
      intake before prescribing supplementation in order to avoid fluorosis and
      possible litigation.

PMID- 9520776
TI  - The dental profession: advocates for abused children.

PMID- 9520777
TI  - Child abuse and neglect investigative process.

PMID- 9520778
TI  - Coronal microleakage in conservatively restored endodontic access preparations.
AB  - This study evaluated the coronal microleakage of endodontic access preparations
      restored with glass ionomer cement (GIC), composite resin (CR), or the "sandwich"
      (GIC/CR) techniques. The size of access preparation for 32 freshly extracted
      maxillary premolars was standardized by using a stainless steel template. The
      teeth were randomly divided into three experimental groups of 10 teeth and one
      group of two control teeth. Group One: light cured glass ionomer cement, Vitra
      Bond (3M Dental Products Division, St. Paul, MN). Group Two: composite resin,
      Silux Plus (3M Dental Products Division, St. Paul, MN). Group Three: "sandwich"
      technique, consisting of a 3 mm glass ionomer cement base and composite resin
      restoring the remaining access. The restorative materials were placed
      incrementally and cured from the facial, lingual and occlusal planes for 20
      second intervals. The teeth were thermocycled for 24 hours, immersed in methylene
      blue dye for 48 hours, and then sectioned to measure dye penetration. This study
      differed substantially from similar leakage studies. The "sandwich" (GIC/CR) and
      the composite resin restorations allowed significantly less coronal leakage than
      the glass ionomer cement restorations. Although not statistically significant,
      less leakage was measured with the "sandwich" restoration than the composite
      resin restoration.

PMID- 9520779
TI  - Microleakage of cervical restorations using two resin bonding systems.

PMID- 9520780
TI  - Association of periodontal disease and histologic lesions in multiple organs from
      45 dogs.
AB  - Forty-five mixed breed dogs were evaluated for the presence and extent of
      periodontal disease. Histopathology was performed on samples of lung, myocardium,
      liver, kidney, tonsil, spleen, submandibular lymph node and tracheobronchial
      lymph node. Mitral valves were evaluated grossly. Statistical analysis was used
      to determine if there was a relationship between the extent of periodontal
      disease and histopathologic changes in the tissues examined. In the forty-five
      dogs studied, an association was found between periodontal disease and
      histopathologic changes in kidney, myocardium (papillary muscle), and liver.

PMID- 9520781
TI  - The membranous bulge lingual to the mandibular molar tooth of a cat contains a
      small salivary gland.
AB  - The membranous bulge lingual to the mandibular molar tooth was examined
      microscopically in 12 cats and found to contain a small mixed salivary gland.
      Approximate size of the gland was 1.0-1.5 mm bucco-lingually, 3.0-3.5 mm mesio
      distally and 3.0 mm of depth at the largest part. This gland is a tubuloacinar
      gland with multiple small openings through several short ducts to the surface of
      the lingual membrane. Mucous acini were predominant with a few serous demilunes.

PMID- 9520783
TI  - Orthodontic correction of lingually displaced canine teeth in a young dog using
      light-cured acrylic resin.
AB  - Lingually displaced canine teeth is a common malocclusion condition in dogs, the
      treatment of which has been described. Several of the previously reported
      treatment regimens involve the use of potentially harmful (toxic and/or
      dangerously exothermic) substances (methylmethacrylate) or require separate
      anesthetic episodes to make impressions and place the appliance. In this case, a
      dog was treated with directly placed appliances made of non-heat generating light
      cured resin. Treatment required only one anesthetic episode to place the
      appliances and one more to remove them.

PMID- 9520782
TI  - Papillary squamous cell carcinoma in a young dog.
AB  - A rostral maxillectomy was performed to remove an intraoral growth in a 9-month
      old Labrador retriever dog. The growth was initially diagnosed from a biopsy
      sample as an acanthomatous epulis. The opinions of several pathologists were
      obtained postoperatively and a final diagnosis of papillary squamous cell
      carcinoma was made.

PMID- 9520784
TI  - Compound odontoma in a dog.
AB  - Compound odontomas are rare tumors of dental origin. Though benign, their effect
      as a space occupying lesion can be dramatic. A large compound odontoma in the
      caudal right mandible of a five and a half month old dog was managed by surgical
      enucleation of the abnormal tissues. No recurrence was evident 6 months later.

PMID- 9520785
TI  - Idiopathic dental root replacement resorption in old dogs.
AB  - The roots of the teeth of 33 large dogs aged 10 years or older were radiographed.
      These dogs were euthanized for reasons other than oral diseases; dogs with
      obvious dental or periodontal diseases were excluded. The dogs had shown no
      clinical signs related to the teeth and the teeth were macroscopically normal. Of
      the 33 dogs, six had one or more teeth that had abnormally shaped and partially
      resorbed roots, with replacement of root structure by radiographically normal
      trabecular bone. Histological examination of radiographically abnormal roots
      revealed mid-root resorption, without signs of inflammation or hypercementosis.
      These findings are similar to the condition known as idiopathic dental root
      replacement resorption in the human dental literature. Possible etiologies of
      root resorption are discussed.

PMID- 9520787
TI  - Electronic programs and information on veterinary dentistry. Special report.
AB  - Veterinary dental materials (e.g. documents, images, continuing education
      courses, message boards, bibliographic search options) that are available as
      electronic media are described. These include materials available on the Internet
      or via commercial on-line services such as AOL-VIN and Compuserve-NOAH, and off
      line materials such as CD-i, CD-ROM and floppy disk programs.

PMID- 9520786
TI  - Correlation of diet, other chewing activities and periodontal disease in North
      American client-owned dogs.
AB  - In 1350 client-owned dogs in North America, the association of calculus, gingival
      inflammation and periodontal bone loss with diet (dry food only, or other than
      dry food only), and with access to other chewing materials was analyzed. There
      were few apparent differences seen in dogs fed dry food only compared with those
      fed other than dry food only. There was progressively less accumulation of
      calculus, less gingival inflammation and less periodontal bone loss in dogs that
      were given access to more types of chewing materials (rawhides, bones, biscuits,
      chew toys) compared with dogs given access to fewer or no chewing materials. When
      the effects of individual chewing materials were analyzed, access to rawhides
      overall had the greatest apparent periodontal protective effect, and this effect
      was more apparent in dogs fed dry food only compared with those fed other than
      dry food only.

PMID- 9520788
TI  - Detection of pathogen-related oral spirochetes, Treponema denticola, and
      Treponema socranskii in dental plaque from dogs.
AB  - Spirochetes have been observed in dental plaque from dogs, but specific
      spirochetes have not been identified. In particular, it is not known whether
      treponemes associated with periodontal diseases in humans also occur in dogs, and
      whether, like in humans, detection of specific treponemes correlates with
      periodontal status of dogs. Forty-two dogs were grouped according to the worst
      periodontal condition in the mouth, as determined by overt signs of inflammation
      and pocket probing depths. A representative specimen of dental plaque was
      obtained by pooling subgingival plaque collected from three uniform reference
      sites, irrespective of periodontal status at selected sites. The presence of
      pathogen-related oral spirochetes. Treponema denticola, and T. socranskii was
      determined using specific monoclonal antibodies in an immunocytochemical
      microscopic assay. All three treponemes were detected in all groups, but a
      significantly greater proportion of dogs with pocket probing depths > or = 5 mm
      had detectable treponemes, compared to dogs that were in periodontal health.

PMID- 9520789
TI  - The role of tooth-brushing and diet in the maintenance of periodontal health in
      dogs.
AB  - Tooth-brushing every other day did not maintain clinically healthy gingivae in
      dogs. The daily addition of a dental hygiene chew to a regimen of tooth brushing
      every other day reduced the gingivitis scores and reduced the accumulation of
      dental deposits (plaque, calculus and stain). Daily tooth-brushing should be the
      recommendation to the dog owner irrespective of dietary regimen. Providing a
      dental hygiene chew daily seems to give an added health benefit when tooth
      brushing is less frequent, and provides the pet owner with a useful adjunct for
      homecare.

PMID- 9520790
TI  - Endodontic therapy and surgical excision of a chronic suppurative osteomyelitic
      lesion in a horse: a case report.
AB  - A 22-year-old thoroughbred gelding was presented for evaluation and treatment of
      chronic dental disease. The horse had a history of quidding and abnormal bite
      behavior. Intraoral examination revealed signs of chronic generalized gingival
      inflammation and severe dental caries affecting the maxillary and mandibular
      incisor teeth. Treatment was provided on two separate visits over an interval of
      four months. The first visit consisted of the surgical extraction of three
      unrestorable incisor teeth and restoration of six carious maxillary incisor
      teeth. The second visit consisted of conventional endodontic therapy on the
      remaining mandibular incisor teeth and the surgical removal of a chronic
      suppurative osteomyelitic lesion. Immediate and long term improvements in eating
      habits were noted. Three month follow-up examinations following completion of
      treatment have shown the teeth to be in functional position, the restorations
      intact, and the surgical site well healed.

PMID- 9520791
TI  - Surgical removal of a radicular odontogenic cyst in a four-year-old Dalmatian
      dog.
AB  - A cystic structure was identified radiographically in a four-year-old dog during
      routine dental prophylaxis. Surgical removal of the cyst lining was achieved by
      exposure of the site through extraction of the right first to third maxillary
      incisor teeth (101, 102, 103). The cyst lining was removed en-bloc. The cavity
      was curetted and filled with decalcified freeze-dried bone. Histological
      examination revealed a radicular cyst. The proposed etiology is blunt trauma to
      tooth 103, pulpal necrosis, apical granuloma and resulting cyst formation.
      Fourteen months following surgery, there was no recurrence of the cyst.

PMID- 9520792
TI  - Apicoectomy on an incisor tooth of a Victorian koala (Phascolarctos cinereus
      victor).
AB  - An eight-year-old Victorian koala was presented with a discharging mandibular
      sinus of at least one month duration. On examination, a dental abscess of the
      right mandibular incisor tooth was found. During the course of endodontic
      treatment, a size 2 Gates Glidden bur separated from the shank and was lodged in
      the canal. Due to the anatomy of the tooth the bur could not be removed and an
      apicoectomy was performed. Following the apicoectomy (follow-up period two
      years), the periapical pathology resolved.

PMID- 9520793
TI  - Report of practicing dentists' activities which serve older people residing in
      Kentucky's nursing homes.
AB  - This state-wide study of dental consultants to nursing homes provides a "first
      ever" profile of this small but important field in dentistry. As the number of
      older people continues to grow, particularly in the 85+ age group (which is most
      likely to be housed in nursing home facilities), the dental profession needs to
      understand and appreciate its professional obligations to this group of "special"
      patients. While the data is not absolutely clear, it does appear that perhaps 50%
      of all of the nursing homes in Kentucky do not have regular staff dentists
      working with them. Surprisingly, no dental hygienists seemed to be working with
      dentists, even though they could be quite useful for several types of clinical
      services and could be a big help with family and staff education projects.
      Nursing home consultants are dedicated individuals in the middle of their
      careers. Although gerontology in general and nursing home care, in particular, is
      primarily a women's field, women dentists in Kentucky are not yet very active in
      this aspect of dental practice. The list of problems and frustrations facing
      dentists seems long and difficult to resolve. In spite of this, the dentists
      working with nursing homes have continued their relationship for many years.
      While some dentists support more than one nursing home facility, the majority of
      the dental consultants do limit their efforts to a single nursing home.

PMID- 9520794
TI  - Theory and reality.

PMID- 9520795
TI  - Back to schools. Phoenix health system finds poor families more trusting of
      school-based centers.
AB  - Low-income families tend to trust school clinics to care for their kids, leading
      one Phoenix health care executive to ask why the model isn't more common. His
      system supports five school health centers that treat hundreds of kids too rich
      for Medicaid, yet too poor for private insurance.

PMID- 9520797
TI  - Pharmaceuticals. Drug companies of choice.

PMID- 9520796
TI  - A friend's legacy of life.

PMID- 9520798
TI  - Education. Schools are out.

PMID- 9520799
TI  - Philanthropy. Rankings change.

PMID- 9520800
TI  - Employers. Costs hold steady.

PMID- 9520801
TI  - Burned on the street.
AB  - Whoosh! That's the sound of once high-flying health care stocks going up in
      flames. Oxford Health Plans, Columbia/HCA, PacifiCare, MedPartners, and other
      notables had a rough year--and they're hardly out of trouble yet. In the
      aftermath, analysts expect major strategic retrenching.

PMID- 9520802
TI  - Service means business. Low rates once ensured lots of patients. Not anymore.
AB  - Health care is seeing a revival of customer service, driven by cost pressure,
      competition, and a nagging conscience to do the right thing. In some markets,
      health systems no longer compete on prices. They're already cut to the bone.
      Service is how they aim to set themselves apart.

PMID- 9520803
TI  - Doctors & unions. United they fell.

PMID- 9520804
TI  - Mental health. Short stays or short cuts?

PMID- 9520805
TI  - Medical waste. Burning issues.

PMID- 9520806
TI  - Voice recognition. Just say the word.

PMID- 9520807
TI  - Efficacy and safety of inhaled corticosteroids. New developments.

PMID- 9520808
TI  - Role of tumor necrosis factor-alpha in small intestinal microcirculation.
AB  - The systemic manifestations of sepsis are associated with increased cardiac
      output, peripheral vasodilatation, and mesenteric vasoconstriction. Our objective
      was to determine whether tumor necrosis factor (TNF)-alpha regulates small
      intestinal microcirculatory changes observed during sepsis. An intact loop of
      terminal ileum of an anesthetized rat was exteriorized into modified Krebs
      solution and then topically suffused with varying concentrations of TNF-alpha
      (10(-4) ng/ml to 10(2) ng/ml), norepinephrine (10(-4) M), and sodium
      nitroprusside (10(-5) M). Videomicroscopy was used to measure arteriolar (A1, A2,
      A3) and venular (V1, V2) diameter changes in response to topical TNF-alpha. First
      order vessel diameters did not change in response to TNF-alpha. However, second
      and third order arterioles dilated maximally by 35 +/- 16 and 52 +/- 12 per cent,
      respectively, in a dose dependent manner in response to TNF-alpha. Higher order
      vessels were more sensitive to TNF-alpha than lower order vessels. Norepinephrine
      (10(-4) M) produced vasoconstriction in all vessels tested (A2 18 +/- 3 per cent,
      p < 0.05; A3 6 +/- 6 per cent; V2 13 +/- 4 per cent, p < 0.05). Topical TNF-alpha
      caused dilation in preconstricted vessels as in the nonpreconstricted vessels.
      TNF-alpha induced vasodilation was prolonged and not reversed by removal of TNF
      alpha. These data demonstrate statistically significant dilation in response to
      TNF-alpha in second and third order arterioles and venules of the small
      intestine. Persistent vasodilation suggests an induced mechanism of vasodilation
      in response to TNF-alpha that remains active even after removal of exogenous TNF
      alpha. We, therefore, conclude that TNF-alpha causes persistent vasodilatation
      beyond the period of actual exposure to TNF-alpha in the small intestinal
      microcirculation. This effect is not altered by the presence of norepinephrine.
      These data suggest that small intestinal vasoconstriction observed during
      clinical conditions such as sepsis is unlikely to be mediated by TNF-alpha.

PMID- 9520809
TI  - Surgical and nonsurgical management of primary and metastatic liver tumors.
AB  - The medical records of 267 patients who had liver tumors, primary and metastatic,
      from 1988 to 1995 were retrospectively reviewed. Two hundred thirteen patients
      (80%) had metastatic disease, and 54 patients (20%) had primary liver disease.
      Their clinical manifestations and laboratory values were evaluated as factors
      predictive of diagnosis and survival. There was a significant increase in the
      occurrence of upper abdominal pain, weight loss, extrahepatic symptoms due to the
      metastatic origin, and hepatomegaly. Metastases from colorectal primary lesions
      were synchronous in 34 patients and metachronous in 31 patients. Stomach, lung,
      and pancreatic primaries were more commonly synchronous. Breast metastases were
      more commonly metachronous. Elevated serum glutamic-oxaloecetic transaminase and
      alkaline phosphatase and decreased albumin were the most common liver test
      abnormalities at diagnosis. Carcinoembryonic antigen values were elevated in the
      majority of colon cancer patients. Eighty-one percent of patients with primary
      liver cancer had elevated levels of alpha-fetoprotein, 40 per cent were
      seropositive for hepatitis B, and 23 per cent were seropositive for hepatitis C.
      Seventy-nine patients (30%) underwent surgery for their cancer, 37 (47%) had
      resections, 38 (48%) were unresectable, and 4 (5%) underwent liver
      transplantation. The patients who underwent surgery had a 32 per cent 5-year
      survival rate compared to a 0 per cent 5-year survival in the patients who did
      not have surgery (p = 0.0001). The patients who had resections had a better
      survival rate than those deemed unresectable at surgery (62% versus 0% at 5-years
      with p = 0.0008). The perioperative morbidity rate was 16 per cent, with
      lobectomies having the best rate and trisegmentectomies having the worst.
      Perioperative mortality rate was zero for all liver resections. Hepatic resection
      and, in selected patients, liver transplantation are the only two available
      therapeutic modalities that produce long-term survival with a possible cure in
      patients with primary and metastatic liver tumor.

PMID- 9520810
TI  - Penetrating neck trauma: lack of universal reporting guidelines.
AB  - Penetrating neck injuries constitute a heterogeneous group. Two different
      classifications of zones of the neck exist in trauma literature. Injuries
      crossing the midline are not accurately reported. Records of 50 patients with
      stab wounds (30), gunshot wounds (GSWs; 17), and shotgun wounds (SGWs; 3) were
      reviewed. Injuries involved zone I in 8 patients, zone II in 37 patients, zone
      III in 8 patients, posterior triangle in 6 patients, and multiple zones in 5
      patients. All 11 patients with transcervical GSWs and SGWs sustained vascular or
      aerodigestive injuries and had longer hospital stays (14.0 +/- 2.6 days) compared
      with patients with other GSWs (6.6 +/- 2.0 days) and stab wounds (3.6 +/- 0.5
      days). We emphasize the lethal potential of transcervical GSWs and SGWs. We
      suggest that these particular injuries be reported separately. We recommend the
      universal adoption of one system of classification of neck zones.

PMID- 9520811
TI  - Management of renal trauma at a rural, level I trauma center.
AB  - Appropriate management of renal trauma is controversial. Successful outcome and
      long term complication rates are not well defined. In an effort to evaluate
      management options, outcomes, and complications of renal injuries, we conducted a
      retrospective review of all trauma patients admitted to the trauma service from
      January 7, 1989 through August 31, 1995. Inpatient and outpatient charts were
      reviewed for type and mechanism of injury, radiologic studies utilized, method of
      treatment, and short and long term complications. Fifty-five patients were
      identified with renal injuries. Most injuries were parenchymal injuries due to
      blunt trauma. Only nine patients with renal artery injuries and four patients
      with collecting system injuries were identified. CT scan was the most commonly
      used study to identify renal injuries. All nine renal artery injuries were due to
      blunt trauma and were initially diagnosed by CT scan. Six were confirmed with
      arteriogram, and two with renal scans. Of the seven patients seen in follow-up
      (average 153 days), there were three complications: one patient with small bowel
      obstruction and two patients with hypertension. Among the 47 patients with
      parenchymal injuries, including 4 patients with collecting system injuries, there
      were 2 with complications: an intraoperative ureteral transection and a urinoma.
      Both complications were treated successfully with a ureteral stent. Five deaths
      occurred in the entire group; none were related to renal injury. Thirteen
      patients underwent laparotomy for associated injuries only. Eight patients
      underwent surgical treatment for their renal injury, including five
      nephrectomies. The nephrectomy rate among those patients who underwent laparotomy
      as part of their initial management was 20 per cent, versus 3 per cent for those
      patients initially managed nonoperatively. Thus, most renal injuries can be
      managed nonoperatively with a low incidence of complications. The incidence of
      long-term complications after renal artery injuries and the appropriate
      management of these patients deserves further study.

PMID- 9520812
TI  - Should a laparoscopic appendectomy be done?
AB  - For a laparoscopic appendectomy to be part of a surgical armamentarium, it
      should: 1) decrease hospital stay, 2) lessen narcotic requirement, 3) speed
      return to normal activity, 4) be cost effective, and 5) have fewer complications.
      To this end, we reviewed 60 consecutive cases of each appendectomy performed,
      laparoscopically and by open technique, during the period of 1993-1996. We looked
      not only at the above criteria, but also at the type of employment. Laparoscopic
      appendectomy did not decrease hospital stay (2.1 versus 1.4 days), or morphine
      equivalent narcotic requirement (38.5 mg versus 19.8 mg). However, laparoscopic
      appendectomy did carry a hospital bill of $3650.00 more than the open technique
      ($7923 versus $4273). This results not only from chargeable disposable items, but
      also from an increase in operative time (47 vs. 36 minutes) and room and
      anesthesia time (88 vs. 63 minutes), because of the increased length of
      preparation time. In only one category, patients involved in heavy manual
      activity (17 patients), the return to normal activity decreased by 1 week. There
      was no difference in complication rate in each category. Based on these findings,
      laparoscopic appendectomy cannot be recommended in suspected cases of
      appendicitis.

PMID- 9520813
TI  - Thyroid lymphoma: is there a role for surgery?
AB  - The role of surgery in the treatment of Stage I and II non-Hodgkin's thyroid
      lymphoma (NHTL) is not well defined. At our institution, we have treated seven
      patients (six women and one man) with NHTL during the past 6 years. Three
      patients (43%) had a prior history of thyroid disease, usually lymphocytic
      thyroiditis. Clinical symptoms included a rapidly enlarging neck mass (86%),
      dysphagia (71%), dyspnea (71%), and hoarseness (71%). Five patients (71%) had
      hypothyroidism; one patient, hyperthyroidism; and one patient, normal thyroid
      function. Five patients underwent fine-needle aspiration (FNA) at our
      institution. In three instances, FNA results were indicative of NHTL; the
      remaining FNA tests yielded no diagnosis. Surgical procedures were varied:
      incisional biopsy (n = 4), limited tumor debulking with tracheostomy (n = 2), and
      thyroidectomy (n = 1). Each of the seven patients was found to have large cell
      lymphoma. Treatment consisted of combination chemotherapy with consolidative
      irradiation. All tumors dramatically decreased in size soon after the initiation
      of therapy. One patient refused radiotherapy. All patients except one are still
      alive (median follow-up, 24 months). In conclusion, 1) a diagnosis of NHTL,
      although rare, should be considered when patients have rapidly growing goiters;
      2) FNA is a useful first step in diagnosing NHTL; 3) NHTL is exquisitely
      sensitive to both chemotherapy and radiation; 4) surgical intervention is
      generally confined to incisional biopsy with occasional limited pretracheal tumor
      debulking; and 5) when a biopsy is obtained from a patient suspected of having
      NHTL, immediate processing by the pathologist is recommended so that material can
      be obtained for special studies as needed.

PMID- 9520814
TI  - High-output cardiac failure secondary to a brachiocephalic arteriovenous
      hemodialysis fistula: two cases.
AB  - The use of native arteriovenous fistulas for hemodialysis access is important to
      the success of this form of treatment for patients with end-stage renal disease.
      Native fistulas have been shown to provide improved longevity and to have lower
      complication rates when compared to prosthetic graft fistulas. High-output
      cardiac failure related to hemodialysis fistulas is an uncommon complication of
      their usage. Two renal transplant patients who did develop this complication from
      large well-developed brachiocephalic arteriovenous hemodialysis fistulas are
      presented. Both patients underwent successful transplantation and have required
      fistula ligation, with subsequent resolution of their cardiac failure. Native
      fistulas remain the best choice for hemodialysis access, but the clinician should
      remain aware of the possible untoward hemodynamic effects of these fistulas.

PMID- 9520815
TI  - Imipramine overdose complicated by toxic megacolon.
AB  - Tricyclic antidepressants are a class of drugs commonly used for the treatment of
      depression. Tricyclic antidepressants account for approximately 20 to 25 per cent
      of drug overdoses that require acute medical admission. The most common cause of
      mortality is cardiovascular toxicity (e.g., arrhythmia, heart block, or
      hypotension). Other morbidities include conditions secondary to anticholinergic
      effects (central and peripheral) and respiratory complications. Ileus,
      constipation and urinary retention are common peripheral anticholinergic
      sequelae, whereas unusual complications include pancreatitis, intestinal pseudo
      obstruction with cecal perforation, and sigmoid colon gangrene. We report a case
      of imipramine overdose that was complicated by toxic megacolon with an associated
      perforation.

PMID- 9520816
TI  - Long-term survival after locally aggressive anorectal melanoma.
AB  - Anorectal melanoma is a rare disease and, unlike cutaneous melanoma, there are
      few guidelines regarding optimal management. It has a reputation for having a
      poor prognosis, which has been attributed to a delay in diagnosis and to a lack
      of effective systemic therapy. It has also been suggested that the biology of
      this tumor may differ from that of cutaneous melanoma. An interesting case of
      anorectal melanoma is presented which highlights the unique considerations and
      challenges encountered by medical oncologists and surgeons who treat this
      disease.

PMID- 9520817
TI  - The outcome of intestinal fistulae: the Louisiana State University Medical Center
      -Shreveport experience.
AB  - Fistulae arising from the intestinal tract are associated with significant
      morbidity and mortality rates. Most contemporary studies of fistulae report
      mortality rates between 6 and 20 per cent. The major causes of death in these
      patients are sepsis, electrolyte imbalance, and malnutrition. A total of 48
      patients with either external or internal intestinal fistulae were reviewed in
      this study over a 5-year period at the Louisiana State University Medical Center
      at Shreveport. Intestinal fistulae were classified into three types, anatomic
      site, physiologic type, and etiology, to evaluate morbidity and mortality rates.
      We also attempted to evaluate the role of parenteral nutrition in this patient
      population, but our data were inconclusive because of the limited number of
      patients. There was no difference in mortality rates associated with anatomical
      sites. High-output fistulae were associated with a higher mortality rate compared
      to low-output fistulae. Fifty-six per cent of the patients achieved closure. The
      overall mortality rate was 21 per cent. Spontaneous closure rates were lower when
      compared to those in other studies. This was attributed to sepsis, malignancy,
      and history of previous radiation therapy. Management of intestinal fistulae
      includes control of sepsis, correction of electrolyte disturbances, nutritional
      support, and operative intervention if necessary.

PMID- 9520818
TI  - Net hepatic glucose output is normal on postoperative day 1 after liver
      transplantation.
AB  - The liver plays a central role in carbohydrate metabolism and glucose
      homeostasis; therefore, the rapid recovery of glucose homeostasis after liver
      transplantation (LT) is important. The purpose of this study was to evaluate
      hepatic and whole-body glucose production (WBGP) on postoperative day 1 after LT
      using a combination of arteriovenous differences and radioisotope techniques. Two
      groups of female commercially bred pigs with an average body weight of 31.9 +/-
      1.4 kg were studied. A control group (n = 6) underwent laparotomy. A transplanted
      group (n = 6) was submitted to LT. All pigs were instrumented with catheters
      placed in the carotid artery and the hepatic, portal, and jugular vein, and flow
      probes were placed around the hepatic artery and portal vein. WBGP was measured
      by a primed constant infusion of 3-[3H]glucose 1 day postoperatively. Plasma
      glucose was 89 +/- 6 versus 98 +/- 7 mg/dL in the control and transplanted
      groups, respectively. WBGP was increased by 42 per cent in the transplanted group
      (2.54 +/- 0.17 vs 3.62 +/- 0.39 mg/kg.min), but the net hepatic glucose output
      was not different between the control and the transplanted groups (1.53 +/- 0.28
      vs 1.68 +/- 0.31 mg/kg.min). These results demonstrate that net hepatic glucose
      output was not different between the control and transplanted pigs, suggesting
      that LT does not compromise the ability of the liver to produce glucose. However,
      the WBGP was increased by 42 per cent in the transplanted group, suggesting
      either a significant contribution from another organ or a significant
      intrahepatic utilization of glucose.

PMID- 9520819
TI  - Kaposi's sarcoma of the parotid gland in acquired immunodeficiency syndrome.
AB  - Parotid gland enlargement is common in patients infected with the human
      immunodeficiency virus. Although parotitis is the usual histopathological feature
      in such cases, patients with acquired immunodeficiency syndrome are at high risk
      of developing both lymphoma and Kaposi's sarcoma of the parotid gland. Human
      immunodeficiency virus, however, is not detected within the parotid parenchyma
      even in the presence of Kaposi's sarcoma. The pathway of the virus' entry into
      the saliva remains unknown.

PMID- 9520821
TI  - Superior mesenteric artery aneurysm: 45 years later.
AB  - Superior mesenteric artery aneurysms (SMAAs) have been described for the past 100
      years, with the first successful treatment being published in 1953 by Drs. M.E.
      DeBakey and D.A. Cooley. It is now 45 years after this first successful
      treatment, and we have a case study of SMAA that depicts the typical presentation
      and treatment of such an aneurysm. Our SMAA was repaired with proximal and distal
      ligation of the aneurysm, with intestinal viability determined by Doppler probe,
      fluorescein dye and repeated laparotomy in 24 hours. The patient tolerated the
      procedure well, and there were no postoperative sequelae. In general, SMAAs have
      a broad range of treatments, including vessel ligation with or without excision,
      revascularization with primary anastomosis, and obliterative aneurysmorrhaphy. In
      the future, these SMAAs and other visceral aneurysms can be treated with
      transluminally placed endovascular grafts with the combined efforts of the
      vascular surgeon and the interventional radiologist. Our article provides an
      overall examination of SMAAs with a review of the literature.

PMID- 9520820
TI  - Reconstruction of replaced right hepatic artery, to implant a single-catheter
      port for intra-arterial hepatic chemotherapy.
AB  - Intra-arterial hepatic chemotherapy using an implantable subcutaneous port with a
      catheter inserted into the gastroduodenal artery is an acceptable treatment for
      patients with isolated, nonresectable liver metastases from colorectal cancer.
      Because of the common variations of hepatic arterial anatomy occurring in about
      one-half of the patients, this technique will result in complete perfusion of
      both hepatic lobes only in those with "classical" arterial anatomy (Michels type
      I). Many techniques have been described in these situations, usually using a dual
      catheter port with the attendant risk of hepatic misperfusion and arterial
      thrombosis. We herein describe an alternative technique applicable to patients
      with a right hepatic artery arising from the superior mesenteric artery. In this
      technique the right hepatic artery is anastomosed end-to-end with the
      gastroduodenal artery, followed by implantation of a single-catheter port that is
      inserted into the splenic artery.

PMID- 9520822
TI  - Successful management of calyceal fistula following simultaneous pancreas-kidney
      transplantation.
AB  - Calyceal fistula is an unusual complication of renal transplantation. We report a
      case of calyceal fistula after simultaneous pancreas-kidney transplant that
      developed after thrombosis of a lower pole artery. Surgical correction was
      successfully achieved with a lower pole nephrectomy, closure of the involved
      calyces, and placement of a ureteral stent and a pedicle of greater omentum graft
      over the affected parenchyma.

PMID- 9520823
TI  - U tubes and rare hepatobiliary complications.
AB  - U tubes have been used for a wide variety of hepatobiliary problems. We report a
      patient with multiple complications possibly related to the use of a U tube.
      These include secondary biliary cirrhosis, intrahepatic bilomas, and
      enterocutaneous fistula. The relatively rare entities of intrahepatic biloma and
      enterocutaneous fistula are reviewed.

PMID- 9520824
TI  - Hippocrates: the true father of medicine.

PMID- 9520825
TI  - Factors affecting wound complications in repair of ventral hernias.
AB  - Wound-related complications are common after incisional hernia repair.
      Prophylactic antibiotic use, placement of subcutaneous drains, and technical
      factors such as mesh implantation reportedly influence the incidence of these
      complications. Our aim was to study the incidence of wound complications in
      incisional hernia repairs and to determine whether use of antibiotics, drains, or
      mesh influence these rates. Two hundred fifty hernias were repaired in 206
      patients over a 14-year period. Simple repair was performed in 151 patients while
      mesh was used in 99 repairs. Mesh repair was used in larger hernias, required
      longer operating time, and had greater blood loss than simple repair. Twenty
      eight per cent of repairs with mesh were for recurrent hernias compared with 14
      per cent for simple repair (P < .05). Overall, 34 per cent of patients had wound
      related complications. Chronic obstructive pulmonary disease, obesity, steroid
      therapy, and previous wound infection were not associated with increased risk for
      wound complications. The use of mesh and hernia defect > 10 cm were associated
      with significantly more wound complications. The incidence of seroma was
      increased in mesh repairs (21% vs 7%), as were total wound complications (44% vs
      26%; P < 0.05). A suprafascial onlay mesh technique resulted in more frequent
      seroma formation. Patients undergoing mesh repair were more likely to receive
      antibiotics (91% vs 71%) and have subcutaneous drains placed (57% vs 25%; P <
      0.05) compared to simple primary repair. Neither antibiotics nor drains had an
      effect on the incidence of wound complications within each group. Overall, wound
      infections were more frequent when drains were placed. We conclude that repair of
      incisional hernias is associated with substantial risk of wound-related
      complications. Mesh is used for repair of larger and more complex hernias and is
      associated with increased risk of wound complications. Abnormal fluid collections
      are the most frequent problem, but the use of drains does not reduce the
      incidence of these complications.

PMID- 9520827
TI  - Re: Evaluation of minor penetrating duodenal injuries.

PMID- 9520826
TI  - Perioperative vasopressin secretion treated by demeclocycline.
AB  - The purpose of this study was to evaluate the perioperative effects of
      demeclocycline on vasopressin (VP) in patients undergoing surgery, specifically
      coronary artery bypass grafting (CABG). This was a prospective, double-blind
      placebo-controlled clinical study using human subjects in a 575-bed tertiary care
      teaching community hospital. Thirty patients (20 males and 10 females) undergoing
      elective CABG over a 6-month period were randomized preoperatively to receive
      either demeclocycline or a placebo. Each patient received either a total of 1200
      mg daily of demeclocycline or a placebo beginning 5 days preoperatively and
      continuing through postoperative day 2. Urine and serum osmolality, electrolytes,
      and VP levels were measured daily. Perioperative VP levels were significantly
      higher (P = 0.05) in the demeclocycline group despite decreased VP activity. The
      postoperative serum sodium and osmolality remained normal in the demeclocycline
      group and significantly decreased in the placebo group (P < 0.01). The urine
      osmolality increased significantly in the placebo group (P = 0.04) on
      postoperative day 1. We conclude that perioperative administration of
      demeclocycline reliably inhibits the effects of increased VP secretion commonly
      seen in patients undergoing CABG procedures. Applying these findings to surgical
      patients who are at increased risk of complicated fluid and electrolyte problems
      requires further study.

PMID- 9520853
TI  - CACH (Canadian Adult Congenital Heart): meeting an emerging need.

PMID- 9520854
TI  - Canadian children get poor marks on foundation health survey.

PMID- 9520855
TI  - Educational resources for patients--the good, the bad and the ugly.

PMID- 9520856
TI  - Towards a modified cardiopulmonary resuscitation policy.
AB  - This article proposes a modification of a hospital cardiopulmonary resuscitation
      (CPR)/do not resuscitate (DNR) policy that prescribes CPR for all unless a DNR
      order is agreed to by patient and physician. Rather than maintaining CPR as an
      intervention that can be avoided only by a negative order, the proposed modified
      policy supports a positive order, i.e., perform CPR when beneficial unless the
      patient refuses. To provide a clinical basis for an ethical discussion comparing
      the current policy with the modified proposal, a brief review of the outcome of
      CPR in terms of survival to discharge is presented. Two principal observations
      were made. First, regarding overall survival, there is an element of harm for an
      important proportion of those who initially respond to CPR but fail to survive to
      discharge, spending time in the intensive care unit only to have a subsequent
      arrest and death in hospital. Second, a set of point estimates of survival to
      discharge in relation to 11 pre-arrest diagnostic characteristics shows their
      close correlation. The modified proposal should provide a more realistic
      framework within which to evaluate the needs and wishes of patients at this
      difficult and emotional time. This concept is implemented by establishing the CPR
      status of all patients as one component of their positive treatment regimen,
      rather than having CPR as an intervention to be avoided only by the DNR order.
      The author discusses the current and proposed policy relative to their effect on
      patient selection, discussion with patients about CPR, the dilemma that results
      when the patient insists on CPR when it is not recommended and the protection of
      patient autonomy.

PMID- 9520857
TI  - She says, he says: difference or dominance in talk between the sexes.

PMID- 9520858
TI  - Relation of HFE gene mutations, high iron stores and early onset coronary artery
      disease.
AB  - OBJECTIVE: To determine the impact of mutations in the HFE gene (human leukocyte
      antigen H) on predisposition to coronary artery disease (CAD) in patients not
      diagnosed with hereditary hemochromatosis. BACKGROUND: Elevated iron stores can
      predispose to acute myocardial infarction. Two mutations (C282Y and H63D) in the
      novel major histocompatibility complex (MHC) class 1 gene HFE were found in most
      patients with hereditary hemochromatosis causing high iron stores. The effect of
      these mutations on predisposition to CAD has not been investigated previously.
      METHODS: Three hundred patients with a history of myocardial infarction or angina
      pectoris and angiographically documented CAD were studied. Patients were divided
      into two groups: group 1 (150 patients), manifesting early onset CAD and
      presenting with these findings under age 50 years; and group 2 (150 patients),
      presenting for the first time over age 65 years. Prevalence of the C282Y and H63D
      mutations was assessed by molecular analysis, and plasma ferritin was measured
      immunochemically. RESULTS: There was no difference in the prevalence of
      homozygous, heterozygous or compound heterozygous (C282Y/H63D) states between the
      groups. Males in group 1 had higher plasma ferritin than those in group 2 (234 +/
      174 micrograms/L versus 136 +/- 103 micrograms/L, P < 0.0001), but this was not
      significantly different in females (75 +/- 54 micrograms/L versus 92 +/- 73
      micrograms/L, P = 0.26). Ferritin remained higher in group 1 than in group 2
      males after exclusion of mutation carriers (195 +/- 121 micrograms/L versus 109
      +/- 76 micrograms/L, respectively, P < 0.0001), but did not change in females.
      CONCLUSIONS: Higher iron stores were found in males with early onset CAD. This
      association was not related to the C282Y or H63D mutation in HFE. It is suggested
      that association of the MHC locus with delayed onset CAD is probably unrelated to
      HFE in these patients, and that HFE mutations are not a major risk factor in the
      development of high iron stores in early onset CAD.

PMID- 9520859
TI  - The electrocardiogram and the secundum atrial septal defect: a reexamination in
      the era of echocardiography.
AB  - BACKGROUND: Ostium secundum atrial septal defects (ASDs) often present subtly and
      may be a diagnostic challenge to the community physician. Characteristic
      abnormalities of the electrocardiogram (ECG) have been described in adults.
      OBJECTIVE: To determine whether ECG abnormalities are consistently present in
      children with a hemodynamically significant ASD, and their potential for
      differentiating this group from patients with innocent murmurs. DESIGN:
      Retrospective evaluation of clinical characteristics, echocardiographic data, and
      ECGs was undertaken in 67 consecutive children with an ASD (mean age 2.9 +/- 2.8
      years, 63% female) and 77 patients with innocent murmur (mean age 3.2 +/- 2.6
      years, 61% male). Predetermined ECG criteria were derived from adult studies
      (rsR'-V1 with evidence of right ventricular hypertrophy, isolated rsR'-V1, and
      unequivocal right ventricular hypertrophy without rsR'-V1). ECGs were interpreted
      blindly by two observers. RESULTS: In the ASD group 58 (87%) patients had an ECG
      that met predetermined criteria compared with three (3.9%) controls (P < 0.001).
      Completely normal ECGs were found in only four (6.0%) ASD patients compared with
      66 (86%) controls (P < 0.001). The ECG criteria had a sensitivity of 86% (95% CI
      0.784 to 0.947) and a specificity of 96% (95% CI 0.918 to 1.000). When any ECG
      abnormality was considered the sensitivity increased to 94% (95% CI 0.884 to
      0.997) with a decline in specificity to 86% (95% CI 0.779 to 0.935). CONCLUSIONS:
      The ECG is potentially a valuable adjunct to the physical examination in
      differentiating children with an ASD from those with an innocent murmur in the
      primary care setting.

PMID- 9520860
TI  - Interventional management of cardiogenic shock.
AB  - Management of the patient with cardiogenic shock requires rapid confirmation of
      the diagnosis and exclusion of potentially correctable conditions. Early
      echocardiography is helpful to exclude mechanical causes of shock, such as
      unsuspected severe mitral insufficiency. Thrombolytic therapy may help prevent
      shock, but its role in established shock is not clear. Intra-aortic balloon
      counterpulsation may be of value, particularly when used in conjunction with
      reperfusion therapy. Angiography can be performed at relatively low risk in shock
      patients. A window of opportunity is often available where revascularization may
      be of benefit.

PMID- 9520861
TI  - Arrhythmias in patients with mechanical ventricular dysfunction and myocardial
      stretch: role of mechano-electric feedback.
AB  - Patients with dilated cardiomyopathy, ventricular volume or pressure overload, or
      dysynergistic ventricular contraction and relaxation are prone to develop severe
      ventricular arrhythmias. In these patients it has been suggested that the
      abnormal mechanics of contraction can disturb 'mechano-electric feedback', also
      known as 'contraction-excitation feedback', which is defined as the development
      of electrophysiological changes during or after changes in mechanical loading.
      This electrical instability, expressed by significant changes in ventricular
      repolarization and refractoriness and by the development of afterdepolarizations,
      has been variously reported in isolated tissues and isolated ventricles as well
      as in hearts in vivo. Furthermore, it is known that many patients with
      supraventricular tachycardia but otherwise structurally normal hearts can develop
      atrial fibrillation and that atrial arrhythmias frequently occur in the setting
      of acute or chronic increases in atrial size and pressure. It is possible that
      changes in atrial load directly alter the electrophysiological properties of the
      atrium by an analogue mechanism of contraction-excitation feedback. This paper
      reviews the literature concerning mechanoelectric feedback involvement in rhythm
      disorders, with the aim of investigating, through basic and clinical research,
      the clinical and therapeutic implications.

PMID- 9520862
TI  - Thrombolytic therapy for myocardial infarction during menstruation.

PMID- 9520863
TI  - Calcium-dependent inhibition of the sodium-calcium exchange current by KB-R7943.
AB  - The inhibitory effect of KB-R7943 (previously called No 7943) on the outward
      sodium-calcium exchange current was re-examined by applying the drug after
      inducing the outward exchange current rather than before the current onset as has
      been done previously. The outward exchange current was induced by raising the
      extracellular calcium ion concentration, [Ca2+]o, from 0.15 mM to 1.8 mM instead
      of from 0 mM to 1 mM, as has been done previously. Aftertreatment KB-R7943
      inhibited the outward exchange current, and the concentration of KB-R7943
      required to inhibit 50% of the exchange current [IC50] was approximately 3
      microM. This value is 10 times higher than that obtained by pretreatment of the
      drug at 1 mM [Ca2+]o. The new IC50 of 3 microM is close to the values for the
      calcium current (8 microM) and the inward rectifier potassium current (7 microM)
      but is still significantly lower than that for the inward sodium-calcium exchange
      current (17 microM).

PMID- 9520864
TI  - Modulation of L-type calcium current kinetics by sarcoplasmic reticulum calcium
      release in ferret isolated right ventricular myocytes.
AB  - The gigaohm seal patch clamp (whole cell configuration) and an internal perfusion
      technique were used to study the effects of sarcoplasmic reticulum (SR) calcium
      release on L-type calcium current (ICa,L) in ferret enzymatically isolated right
      ventricular myocytes. ICa,L (22 to 24 degrees C) was isolated by using various
      sodium- and potassium-free salines, which eliminated or greatly minimized
      activation of the sodium-calcium exchanger and calcium-activated cation and anion
      currents. When calcium was the charge carrier, inactivation of ICa,L was
      nonmonotonic in many myocytes; after an early rapid phase of inactivation, a
      secondary inward 'hump' component was frequently observed between -40 to -10 mV.
      The hump component was not present when barium replaced calcium but was observed
      when calcium carried the current in low intracellular (aspartate) and
      extracellular (methanesulphonate) chloride solutions. When BAPTA 10 mM was
      perfused internally the amplitude of ICa,L increased, the kinetics of
      inactivation slowed and the hump component disappeared. Both caffeine 10 mM and
      ryanodine 10 microM increased the amplitude of ICa,L in the hyperpolarized range
      of potentials (negative to 0 mV), slowed the kinetics of ICa,L inactivation and
      caused the hump component to disappear. Under current clamp mode, both caffeine
      and ryanodine significantly prolonged the duration of the action potential. Taken
      in aggregate, preliminary data demonstrate that, in ferret right ventricular
      myocytes, a secondary inward hump component can be frequently observed after the
      early rapid phase of inactivation of ICa,L, causing the net inward current to
      display biphasic, nonmonotonic behaviour. This secondary inward hump current is
      only present when calcium is the charge carrier, is absent when BAPTA is used as
      an intracellular calcium chelator and SR calcium release is disrupted by either
      caffeine or ryanodine, and is not due to activation of either the sodium-calcium
      exchanger or various putative calcium-activated cation or anion channels. Rather,
      preliminary results strongly suggest that this secondary inward hump current
      component is due to modulation of ICa,L by SR calcium release. Possible
      physiological and theoretical implications of the results are discussed briefly.

PMID- 9520865
TI  - Voltage-dependent, open channel blockade of the cardiac sarcoplasmic reticulum
      potassium channel by 4-aminopyridine.
AB  - The nature of open state block was characterized in isolated canine cardiac
      sarcoplasmic reticulum (SR) potassium channel incorporated into planar lipid
      bilayers. 4-Aminopyridine (4-AP) blocked the open conductance state of the
      potassium channels in a voltage-dependent manner. Blockade was reversible,
      occurred from either the cis (cytoplasmic) or the trans (lumenal) side and was
      competitive with potassium ions. Reversal potential measurements indicated that
      this channel was impermeable to 4-AP. Measured effective electrical distances
      were roughly symmetrical and indicated penetration of 0.39 and 0.42 of the
      membrane electrical field from the cis and trans sides, respectively. Effective
      electrical distance was insensitive to potassium ion concentration in the range
      50 to 200 mM and indicated that 4-AP was able to penetrate relatively deeply into
      the pore compared with blockade of sarcolemmal potassium channels. Potassium ion
      concentration and voltage dependence of 4-AP blockade were consistent with a two
      binding site blockade model, similar to the model used previously to describe
      calcium ion blockade of the SR potassium ion channel. Unlike calcium blockade,
      however, 4-AP blocked from either cis or trans in a similar manner, suggesting a
      distinct binding site for each of these two blockers. Open channel, voltage
      dependent blockade of the SR potassium channel by 4-AP is in marked contrast to
      its action on sarcolemmal potassium channels and suggests that either 4-AP
      penetrates much farther into the potassium channel permeation pathway than was
      previously believed, or the SR potassium channel has a very different physical
      pore arrangement from that of sarcolemmal potassium channels.

PMID- 9520866
TI  - Potassium current and sodium pump involvement in the positive inotropy of cardiac
      muscle during hyperosmotic stress.
AB  - OBJECTIVE: To identify factors involved in the modification of cardiac
      electromechanical activity caused by hyperosmotic solution. DESIGN: Membrane
      potentials and contractions were recorded from isolated papillary muscles, and
      membrane ionic currents were measured in isolated ventricular myocytes by using
      the ruptured patch or perforated patch voltage clamp method. ANIMALS AND METHODS:
      Adult male guinea-pigs weighing 250 to 350 g were used. Normal Tyrode's solution
      for superfusing experimental preparations was replaced with hyperosmotic Tyrode's
      solution for observation periods of up to 10 mins. The hyperosmotic solution was
      normal Tyrode's solution supplemented with 50 or 150 mM sucrose (1.2 or 1.5 times
      normal osmolality). Sodium pump activity (hyperpolarization in muscles; outward
      current in myocytes) was activated by switching to pump-activating cation
      (cesium, potassium) solution from pump-inactivating potassium-free solution under
      conditions in which other ionic currents were suppressed. RESULTS: Hyperosmotic
      solution lengthened action potentials and enhanced developed tension in papillary
      muscles. Superfusion of myocytes with hyperosmotic solution inhibited inward L
      type calcium current (ICa,L) by approximately 30% and the outward delayed
      rectifier potassium current (Ik) by approximately 50%. Hyperosmotic treatment
      also partially inhibited sodium pump-generated hyperpolarizations in papillary
      muscles. However, sodium pump current in myocytes was relatively small under
      isosmotic conditions and, therefore, unlikely to be a major factor in action
      potential lengthening. CONCLUSIONS: Inhibition of potassium current is a major
      factor in the lengthening of the action potential by hyperosmotic solution. It
      seems likely that the accompanying positive inotropy is due to an elevation of
      intracellular calcium caused by enhanced calcium influx related to action
      potential prolongation and sodium pump inhibition.

PMID- 9520867
TI  - Changes to the health care system: reform or restructuring?

PMID- 9520868
TI  - Advances in operative fracture treatment. A tribute to Martin Allgower and Hans
      Robert Willenegger.

PMID- 9520870
TI  - History of the AO and its global effect on operative fracture treatment.
AB  - In 1958 a group of Swiss general and orthopaedic surgeons established the AO
      (Arbeitsgemeinschaft fur Osteosynthesefragen) or the Association of the Study of
      Internal Fixation (ASIF) to strive to transform the contemporary treatment of
      fractures in Switzerland. This association was revolutionary in development of
      instruments and implants for operative fracture treatment. The first
      instructional course for teaching the use of these instruments and implants
      occurred in Davos, Switzerland, in the newly founded Laboratory of Experimental
      Surgery in 1960. Through a process of internal quality control (AO documentation)
      the clinical success of these new techniques and implants became evident.
      Operative fracture treatment gained acceptance throughout Europe and finally
      worldwide. AO/International (AOI) was founded in 1972 to expand education and the
      teaching programs for surgeons and operating personnel on an international basis.
      In 1984, the AO/ASIF Foundation was created with an AO Board of Trustees
      comprising 90 leading trauma surgeons from throughout the world. Continuous
      research, implant and instrument development, clinical documentation, and
      multifaceted educational opportunities are coordinated by the AO/ASIF Foundation
      to maintain its position as the international authority in the treatment of
      trauma. The medical community recognizes today the enormous positive global
      effect that this respected and ever changing organization has had by continually
      improving operative fracture treatment.

PMID- 9520869
TI  - The application of extension to overlapping fractures, especially of the tibia,
      by means of bone screws and a turnbuckle, without open operation. 1919.

PMID- 9520871
TI  - Indications for intertrochanteric osteotomy after periacetabular osteotomy for
      adult hip dysplasia.
AB  - Residual hip dysplasia in the adult is characterized by deficient anterior and
      lateral acetabular coverage with subsequent hip joint incongruity and
      instability. The frequency of periacetabular osteotomy for the treatment of
      residual hip dysplasia is increasing. In certain morphologic conditions
      preoperative abduction or intraoperative radiographs reveal that congruency after
      a periacetabular osteotomy is not optimum; at this point the surgeon may consider
      the addition of an intertrochanteric osteotomy. In a retrospective study, the
      radiographs of 25 patients who had a femoral osteotomy with or after
      periacetabular osteotomy were analyzed and the results were compared with a
      control group of 34 patients who had periacetabular osteotomy without a femoral
      osteotomy. The analyzed parameters included: the femoral head extrusion index and
      the acetabular index, before and after periacetabular osteotomy; the femoral neck
      shaft angle; the presence of femoral head deformity; the presence of
      osteoarthrosis; the presence of a secondary acetabulum; the influence of previous
      ipsilateral hip surgery; the effect of hip adduction or abduction on joint
      congruency; and the age of the patient. The variables that had a statistically
      significant association with the performance of an intertrochanteric osteotomy
      included a femoral head extrusion index and an acetabular index after
      periacetabular osteotomy outside the normal limits, a neck shaft angle outside
      the limits of the control group, a deformed femoral head, an osteoarthritic hip,
      a secondary acetabulum, and a joint space height and congruency dependent on
      position of the proximal femur. When using statistically significant variables, a
      discriminant analysis predicted the correct group (periacetabular osteotomy with
      femoral osteotomy, or periacetabular osteotomy without femoral osteotomy) for 89%
      of the cases.

PMID- 9520872
TI  - New techniques in indirect reduction of long bone fractures.
AB  - The most important and demanding part of operative fracture treatment concerns
      the reduction and correct alignment of the fracture fragments, which must be
      gentle to the bone and surrounding soft parts to preserve the essential blood
      supply to all tissues. The so called indirect reduction techniques apply the
      principles of nonoperative fracture care (ligamentotaxis) in combination with
      surgical tools and a number of techniques, where by the exposure of the most
      critical fracture focus can be minimized. New implant designs, low contact
      plates, cannulated screws, unreamed nails, pinless and hybrid external fixators,
      are helpful adjuncts: however, the surgical technique remains of paramount
      importance. The essence of careful handling of the soft and hard tissues has been
      stressed time and again. With the introduction of biological or minimally
      invasive surgery, the techniques of indirect reduction have had a renaissance. A
      few examples are described.

PMID- 9520873
TI  - Pinless external fixation. Indications and preliminary results in tibial shaft
      fractures.
AB  - A major drawback of conventional fixator systems is the penetration of the
      fixator pins into the medullary canal. The pins create a direct link between the
      medullary cavity and the outer environment. The new AO pinless fixator bypasses
      this disadvantage by clamping its trocar points onto the outer cortex without
      penetrating it. Thus, exposure and consequent contamination of the medullary
      cavity does not occur. The clinical use of this easily manageable fixator with no
      drilling requirement is for tibial fractures in which the general and local
      conditions are poor or the infrastructure of the clinic is inadequate for primary
      internal stabilization or both. All options for a later conversion to internal
      fixation remain open. For highly unstable tibial shaft fractures, the pinless
      fixator can be applied as an additional, minimally invasive, external, locked
      system to increase the stability of intramedullary nail fixation. The pinless
      external fixator can be combined favorably with the standard AO tubular system
      and is a valuable addition to the existing fixator systems.

PMID- 9520874
TI  - Fractures of the distal femur revisited.
AB  - The treatment of supracondylar fractures is presented, including the most recent
      developments. The author uses the comprehensive classification of these fractures
      and explains the method of this classification scheme as a guide to treatment.
      New surgical approaches and a discussion of the surgical anatomy are presented in
      detail. The traditional and contemporary methods of reduction and fixation are
      discussed, and how the need to preserve the blood supply to the soft tissues and
      bone has led to the development of the modern methods. The biologic and
      biomechanical reasons for absolutely stable fixation for simple fractures and
      splinting with bridging plates, the so called bridge plating of multifragmentary
      fractures are explained as are the technical details of fixation. Discussed in
      detail are specific variations in treatment methods for the particularly
      difficult problem of open fractures, fractures above total knee arthroplasty, and
      fractures in osteoporotic bone.

PMID- 9520875
TI  - Treatment of femoral fractures in the multiply injured patient with thoracic
      injury.
AB  - Early fracture fixation in the multiply injured patient has been shown to reduce
      morbidity and mortality. This premise recently has been questioned when the
      multiply injured patient has a pulmonary contusion, and also has a femoral
      fracture stabilized with a reamed intramedullary nail. This put into question
      whether early stabilization of femoral fractures, especially with a reamed
      intramedullary nail, should be performed in patients with a pulmonary contusion.
      A review of the most recent clinical and animal research was performed to help
      answer this question. This review has revealed that the incidence of pulmonary
      failure and adult respiratory distress syndrome in multiply injured patients with
      thoracic injuries who have femoral fractures treated acutely is less than 3%. The
      morbidity associated with patients with pulmonary contusions is independent of
      the treatment of the femoral fracture. No difference in the rate of pulmonary
      failure is found with reamed nails or plate fixation. The pulmonary failure seems
      to be secondary to the pulmonary contusion, not to the method of fracture
      fixation.

PMID- 9520876
TI  - Internal fixation of multiple fractures in patients with polytrauma.
AB  - Within the last decade understanding of the pathogenetic consequences of trauma
      has been improved significantly. An additional reduction of lethality has been
      achieved that in part is related to increasing discrimination of complex injury
      patterns. Accordingly, additional staging in fracture management of these
      injuries has been developed. An overview of the current status of fracture
      management in polytrauma is given and certain regimens that are still
      controversially are discussed. The principles determined are based on the
      treatment experience of 4003 multiply injured patients within the past 23 years.
      The most important principles within the first hours after trauma represent
      adequate hemorrhage control. In fracture treatment the primary goal remains to
      perform primary stable osteosynthesis. In severe polytrauma with severe injuries
      to the extremities, the first decision is whether limb salvage can be achieved
      without risk of deterioration of the patient's condition. If this is the case,
      open fractures Grades III b and c usually can be stabilized primarily by unreamed
      intramedullary nailing or percutaneous plating. The priority pattern in multiple
      closed fractures is as follows: (1) tibia; (2) femur; (3) pelvis; (4) spine; and
      (5) upper extremity. Exceptions may ensue if severe head or thoracic trauma is
      present. Delayed treatment is performed for complex joint reconstruction,
      definitive treatment of maxillofacial injuries, and soft tissue reconstruction.

PMID- 9520877
TI  - Biomechanical evaluation of the schuhli nut.
AB  - The schuhli out is a device designed to lock an AO 4.5-mm cortical screw to a 4.5
      mm dynamic compression plate independent of bony contact with the plate. The nut
      engages the screw below the plate, elevating the plate, and locking the screw at
      a 90 degrees angle, thus preventing toggling. Photoelastic modeling and
      biomechanical testing on sheep tibias were done to determine the mechanical
      properties of constructs using schuhli nuts. Use of schuhli nuts was shown to
      decrease stress in the bone below the plate. The initial axial stiffness of a
      construct fixed with schuhli nuts is less than a construct with standard screws,
      but the rate of loss of stiffness with cyclic loading is similar. When a cortical
      defect is present at the near cortex and the screw engages the far cortex only,
      the use of a schuhli nut significantly improves the stability of the construct
      compared with a standard screw alone, and behaves mechanically the same as a
      standard construct with intact cortices. This indicates that the schuhli nut acts
      as a substitute for a deficient cortex. The schuhli nut can be useful in
      osteoporotic bone because it prevents the screw from stripping the threads in the
      bone as the screw is advanced. It also serves to lock the screw to help prevent
      the screw from backing out. The schuhli nut may be a useful tool to improve
      stability in the treatment of complex fractures, reconstructions, or in
      pathologic bone.

PMID- 9520878
TI  - Patients treated for nonunions with plate and screw fixation and adjunctive
      locking nuts.
AB  - Locking nuts were used as an adjunct to plate fixation in 48 procedures in 44
      patients. All the procedures were done by one surgeon during a 4-year period. The
      patients in this study were treated for nonunion or malunion and thus had
      difficult technical problems, such as cortical defects or holes left from
      previous hardware. The use of standard implants were generally unreliable for
      additional fixation. The locking nuts were used as a cortical substitute in 26
      instances, to create a fixed angle relationship between the plate and the screw
      in 14 instances, to elevate the plate off the bone to help increase vascularity
      in five instances, and to increase purchase in severely osteoporotic bone in
      three instances. Complete followup was obtained on 43 of the 44 patients. Forty
      of the 43 patients achieved complete union after their reconstructive procedure.
      Three patients had continued nonunions with eventual hardware failure and
      required reoperation. The use of the locking nuts enabled the surgeons to obtain
      stable fixation at the time of reoperation with eventual union of all of the
      ununited bones. The success of the use of this implant is best gauged by the fact
      that the surgeon could place screws effectively where cortical defects existed,
      allow improved purchase in osteoporotic bone, and create a fixed angle plate
      screw relationship that would have been difficult to do without the locking nuts.

PMID- 9520879
TI  - Operative management of diaphyseal fractures of the humerus. Plate versus nail.
AB  - Although nonoperative treatment is indicated and successful for the majority of
      diaphyseal humeral fractures, operative intervention is indicated in several
      situations. Either intramedullary nail or plate fixation commonly is used for the
      operative management of this problem. Familiarity with the surgical techniques
      and application of both types (and subtypes) of implants is necessary to allow
      optimal treatment for the widest range of fracture patterns. In most indications
      for operative management, internal fixation with plates is preferred. Stable
      fixation, sparing adjacent joints from iatrogenic injuries, and direct
      visualization and protection of the radial nerve are of critical importance in
      maximizing postoperative function and in most cases outweight the potential
      advantages of a loadsharing implant inserted through a more limited incision.

PMID- 9520880
TI  - One-stage lengthening of femoral nonunion augmented with human bone morphogenetic
      protein.
AB  - Fifteen patients with posttraumatic shortened atrophic femoral nonunions were
      treated with one-stage lengthening. The alloimplant was composed of allogeneic
      antigen extracted autolyzed human bone perfused with partially purified human
      cortical bone morphogenetic protein associated with noncollagenous protein and
      used as graft. The composite was lyophilized and sterilized with ethylene oxide.
      All 15 nonunions were atrophic diaphyseal and were lengthened through intercalary
      segmental defects bridged with the human bone morphogenetic protein composite
      alloimplants stabilized to the medial femoral cortex through plate osteosynthesis
      and lag screw fixation. One lengthened proximal femur had fatigue failure of the
      plate and was treated successfully by exchange plating. The average increase in
      length was 2.8 cm (range, 1.5-5 cm) and an average percentage increase in length
      of 8% (range, 4%-132%) of the residual shortened femur. The human bone
      morphogenetic protein composite produced an immediate reactive bone formation in
      the host bone and progressive remodeling of the donor recipient interfaces. There
      were no infections, allergic reactions, clinical rejection of the human bone
      morphogenetic protein composite alloimplants, or evidence of malignant disease.
      One-stage femoral lengthening augmented with human bone morphogenetic protein
      composite graft bridged the intercalary defect, remodeled the atrophic host bone
      and restored bone continuity within 1 to 2 years. Human bone morphogenetic
      protein composite alloimplants are a substitute of autogeneic bone graft and
      offer an alternative to iliac crest bone without the associated morbidity.

PMID- 9520882
TI  - Displaced fractures of the glenoid fossa. Results of open reduction and internal
      fixation.
AB  - Displaced fractures of the glenoid fossa are an uncommon and anatomically diverse
      group of injuries. Failure to restore anatomy in these fractures results in poor
      outcome in most cases. The success of a treatment protocol that encompasses
      appropriate preoperative imaging, injury pattern assessment, prudent approach
      choice, and a comprehensive reduction and fixation tactic was evaluated. Twenty
      seven patients were assessed clinically and radiographically at a mean followup
      interval of 43 months from surgery. Anatomic reconstruction was achieved in 24
      (89%) patients. Three patients had residual joint incongruities measuring 2 mm or
      less. The only perioperative complication was a partial superficial wound
      dehiscence. Two additional patients had infraspinatus palsies of indeterminate
      origin. Functional rating revealed six (22%) excellent, 16 (60%) good, three
      (11%) fair, and two (7%) poor outcomes. The fair and poor outcomes largely were
      related to associated injuries. These findings show that anatomic surgical
      reconstruction with a low complication rate and good functional outcome can be
      obtained for most patients with glenoid fossa fractures.

PMID- 9520881
TI  - Does bacteremia occur during high pressure lavage of contaminated wounds?
AB  - The risk of bacteremia secondary to high pressure lavage of contaminated wounds
      was assessed. Twenty canines were divided randomly into four treatment groups. A
      10-cm incision was made over the left shoulder of each dog. The deltoideus muscle
      was disrupted and traumatized. Groups A and B (n = 8) had wound contamination
      with 1.4 x 10(9) Staphylococcus aureus followed 75 minutes later by high pressure
      lavage or bulb syringe irrigation, respectively. Groups C and D (n = 2) had no
      contamination, followed by the same treatment. Bacterial counts were obtained
      before and after wound irrigation. Blood cultures were obtained before, during,
      and 15 minutes after irrigation. Positive control cultures were obtained during
      injection of bacteria into the antecubital vein. A detectable bacteremia did not
      occur during or after high pressure lavage or bulb syringe irrigation of acute
      contaminated wounds but did occur in 18 of 20 positive controls. Bacterial levels
      were reduced by an average of 70% +/- 10% by high pressure lavage and 44% +/- 50%
      by bulb irrigation. Reduction of wound bacteria was achieved more consistently
      with high pressure lavage than with bulb syringe irrigation.

PMID- 9520883
TI  - Clinical and functional outcomes of internal fixation of displaced pilon
      fractures.
AB  - The clinical and functional outcomes for patients treated with open reduction and
      plate fixation of displaced tibial pilon fractures were determined. A
      retrospective search of the authors' trauma database was conducted for AO and
      Orthopaedic Trauma Association Code 43 injuries (pilon fractures) in adults 18
      years or older who were treated between December 1988 and December 1992. The
      group of 64 patients who required open reduction and internal fixation to treat
      their fractures make up the primary cohort for this analysis. Twenty of these
      cases required no fibular fixation; the remainder were mostly fixed with 1/3
      tubular or 3.5-mm compression plates. Tibial fixation was done using most
      commonly 3.5-mm cloverleaf plates, 1/3 tubular plates, or both. Of the 64
      patients treated with open reduction and internal replacement, four (5%) patients
      had deep infection develop. Two (7%) of 14 patients had open fractures, and two
      (4%) of 50 patients had closed fractures. Three of these four patients smoked
      tobacco products; one was also an intravenous drug abuser. Staphylococcus aureus
      was the organism in two cases; Enterobacter, in the other two. The infection was
      controlled with a free flap in two cases, with antibiotics and wound debridement
      in one and with an arthrodesis in one. Thirty of the 64 patients completed the
      Short Form-36; two of these patients had bilateral fractures. The study group had
      significant differences in general health perceptions, physical function,
      physical role function, emotional role function, social and mental function, and
      pain and energy levels when compared with age matched population data and
      patients with tibial plateau fractures. The effect of other injuries on these
      functional status results cannot be determined specifically.

PMID- 9520885
TI  - Arthroscopic microdiscectomy and selective fragmentectomy.
AB  - A prospective outcome study to determine the efficacy and complications
      associated with posterolateral arthroscopic discectomy was initiated in April
      1988. One hundred seventy-five patients with symptoms consistent with a lumbar
      disc herniation and correlative imaging studies were treated operatively, and 169
      were available for followup evaluation. Fifty-nine patients with a central
      herniation or a nonmigrated sequestered fragment were treated using bilateral
      biportal posterolateral access, whereas 116 patients with radiographic evidence
      of a paramedial, foraminal, or extra-foraminal herniation were treated using the
      unilateral uniportal approach. The minimum duration of nonoperative management
      ranged from 3.5 to 28 months (average, 16 months), and all patients had a minimum
      of 24 months of postoperative followup. Outcome analysis indicated that 149
      procedures were successful, whereas 20 (11.8%) procedures were failures because
      of persistent radicular symptoms that, in some cases, required open laminotomy.
      Complications associated with the procedures included one disc space infection,
      one transient peroneal neuropraxia, and four index extremity skin
      hypersensitivity. All of these complications resolved without sequelae, and there
      were no neurovascular complications directly related to the surgical approach.

PMID- 9520884
TI  - Reconstruction of chronic and complete dislocations of the acromioclavicular
      joint.
AB  - The authors report on a technique for the treatment of symptomatic, chronic
      complete dislocations of the acromioclavicular joint. The coracoacromial ligament
      is substituted for the coracoclavicular ligaments, and a special temporary
      coracoclavicular lag screw is used to stabilize the clavicle to the coracoid
      during ligament healing. The technique has been used on 23 patients who were
      observed for an average of 5.2 years. Good to excellent results were obtained in
      19 of 23 patients. The four patients with fair or poor results had one or more
      resections of the distal clavicle before the reconstruction. Subjectively, 22 of
      23 patients reported improvement in their shoulder.

PMID- 9520886
TI  - Revision of loose cementless femoral prostheses to larger porous coated
      components.
AB  - The results of 21 revision hip arthroplasties were reviewed. The indication for
      each revision was a symptomatically loose porous coated femoral component. The
      loose stems were all replaced with Anatomic Medullary Locking stems. In 16 of the
      21 procedures, the acetabular component also was revised. Complications included
      two intraoperative femoral fractures, one sciatic nerve palsy, and one case of
      multiple hip dislocations. The mean Harris Hip Score was significantly improved
      from a mean of 42 points (range, 23-90 points) preoperatively to a mean of 84
      points (range, 59-100 points) 6.3 years after the revision. Ninety-five percent
      of the patients reported less severe hip pain. Ninety percent had improved
      walking ability. Eighty-five percent stated that they were satisfied with the
      results of the revision procedure. No femoral component has shown radiographic or
      clinical signs of repeat loosening, and none have been rerevised. It was
      concluded that when a cementless femoral component becomes symptomatically loose,
      replacing the loose stem with a larger and more extensively porous coated
      component is a successful method for achieving better implant fixation.

PMID- 9520887
TI  - Clinical and pathologic findings in hemochromatosis hip arthropathy.
AB  - During a 9-year period, 15 patients with hemochromatosis hip arthropathy required
      19 total hip arthroplasties for disabling hip pain. Preoperative presentation,
      hip function, pathologic evaluation of the femoral head, and radiographic
      findings were reviewed. Postoperative followup averaging 5.7 years (range, 2-11
      years) was performed to assess hip pain and function after total hip
      arthroplasty. The average preoperative Hospital for Special Surgery hip score was
      15 points (range, 4-24 points), and this improved to 30 points (range, 4-38
      points) after total hip arthroplasty. Only one of 15 patients required revision
      surgery at 10 years for acetabular loosening. All other patients were pain free,
      with improved function at latest followup. Histologic evaluation of the resected
      femoral heads revealed evidence of primary or secondary osteonecrosis in seven of
      19 (37%) specimens. Articular cartilage avulsion at the level of the tidemark was
      identified in eight of 19 (42%) specimens, and calcium pyrophosphate deposition
      was identified in five of 19 (26%) specimens. These pathologic findings suggest a
      predictable progression of the arthritic process in patients with
      hemochromatosis.

PMID- 9520888
TI  - Drainage versus nondrainage in simultaneous bilateral total knee arthroplasties.
AB  - A prospective study of 69 patients (138 knees) who had a primary simultaneous
      bilateral total knee replacement was conducted to assess the effect of
      postoperative suction drainage on wound healing and infection. A suction drain
      was placed by randomization of side for the drained versus nondrained side. The
      same operative technique was used in all wounds of total knee arthroplasty. The
      knees that had no drains had a higher incidence of drainage from the wound, had
      soaked dressings requiring dressing reinforcements, and had more ecchymosis and
      erythema around the wound. However, the final results regarding quadriceps
      strength, range of motion, and wound complications were not affected
      significantly by nonuse of closed suction drainage. Although the incidence of
      infection in the two groups is not statistically different, the development of
      infection in two knees in which drains were not used suggests that suction
      drainage may reduce deep infection.

PMID- 9520889
TI  - Home based rehabilitation for anterior cruciate ligament reconstruction.
AB  - Fifty-four patients who underwent arthroscopically assisted anterior cruciate
      ligament reconstruction with bone-patellar tendon-bone autograft or allograft
      were studied prospectively to compare a postoperative home based rehabilitation
      program with a clinic based program. Fifty-four patients (mean age, 30 years)
      were assigned randomly to the home based program (27 patients) or the clinic
      based program (27 patients). The home based schedule featured six physical
      therapy visits during a 6-month postoperative study period, whereas the clinic
      based schedule specified 24 physical therapy visits during those 6 months. All
      patients entered in the study met strict selection criteria: age older than 15
      years, no previous ligament repair or reconstruction, no complicating medical
      conditions, no collegiate or professional athletes, reconstruction at least 6
      weeks after injury, and informed consent. At the 6-month followup, no significant
      statistical differences were found between the two groups in range of motion,
      thigh atrophy, anterior drawer compliance, hopping tests, Lysholm scores, or
      subjective health status scores. Thus, the authors conclude that in a selected
      group of patients who have undergone anterior cruciate ligament reconstruction, a
      home based postoperative rehabilitation program is feasible, safe, and effective.

PMID- 9520890
TI  - Transtibial amputation for sciatic nerve loss. Saphenous sensate residual limb.
AB  - After permanent loss of the sciatic nerve, most patients eventually have problems
      with the insensate skin and need transitibial amputation. The authors have
      designed a long medial sensate myocutaneous flap down to the foot based on the
      saphenous branch of the femoral nerve that resulted in good sensation over the
      entire transtibial residual limb.

PMID- 9520891
TI  - Common peroneal nerve block for sciatica.
AB  - The effectiveness of common peroneal nerve block for lumbar disc herniation was
      evaluated in a double blind study. Common peroneal nerve block was performed near
      the fibular head in nine patients using 2% lidocaine and in 10 patients using
      saline. The average pain scale score decreased from 3.1 to 0.6 in the lidocaine
      group, whereas it decreased from 3.0 to 2.6 in the placebo group. The average
      result in the straight leg raising test increased from 61 degrees to 84 degrees
      in the lidocaine group, but from 44 degrees to 50 degrees in the placebo group.
      Lower leg pain lessened more in the lidocaine group than in the placebo group.
      The finding that lower leg pain disappeared or decreased with a lidocaine block
      at a site far distal to the lumbar lesion suggests that impulses that are
      transmitted distal to the lesion may be important for the generation of sciatic
      radicular pain.

PMID- 9520892
TI  - Arthrodesis versus resection arthroplasty for failed hallux valgus operations.
AB  - The results for 18 patients (20 feet) in whom a hallux valgus procedure had
      failed were reviewed. Ten patients (11 feet), with a mean age of 63 years, had
      correction with Keller resection arthroplasty and were observed for an average of
      10 years (range, 3-15 years). The hallux valgus angle improved an average of 11
      degrees +/- 3 degrees, and the intermetatarsal angle improved an average of 2
      degrees +/- 1.7 degrees. Results were good in six feet, fair in four, and poor in
      one. Eight patients (nine feet), with a mean age of 63 years, had correction with
      arthrodesis and were observed for an average of 5 years (range, 2-8 years). The
      hallux valgus angle improved an average of 23 degrees +/- 6.9 degrees, and the
      intermetatarsal angle improved an average of 2 degrees +/- 3 degrees. Results
      were good in six feet, fair in two, and poor in one. There were differences
      between the two operations in terms of patient satisfaction, pain relief,
      appearance, and footwear. The incidence of metatarsalgia was similar for the two
      groups. Complications, particularly malalignment, were more common in the
      resection group. None of the patients required additional revision operation.
      Resection arthroplasty is a simple procedure and does not require cast
      immobilization. Resection arthroplasty and arthrodesis are reasonable options for
      salvage treatment of failed hallux valgus operations in older patients because
      good results were achieved in six of nine (67%) feet after arthrodesis and in six
      of 11 (54%) feet after resection.

PMID- 9520893
TI  - Treatment of hip dysplasia in older children with a combined one-stage procedure.
AB  - This retrospective study was conducted to determine the efficacy and complication
      rates associated with treating children of ambulatory age with idiopathic
      developmental dysplasia of the hip with open reduction and combined femoral and
      pelvic osteotomies. Eighteen hips were reviewed in 13 patients. The average
      patient age at surgery was 29 months (range, 15-117 months), with an average
      followup of 43 months (range, 24-78 months). Preoperative Tonnis classification
      identified six Class II, seven Class III, and five Class IV hips. Followup
      Severin classification identified 16 Class 1A and two Class 2A hips. The average
      center edge angle on most recent followup was 47 degrees (range, 25 degrees-70
      degrees), and the acetabular index was 5 degrees (range, 0 degree-20 degrees).
      Avascular necrosis developed in one (5.5%) patient. Clinically, all patients were
      pain free with ambulation and had excellent results by McKay criteria. No patient
      required a second surgical procedure for recurrent subluxation or persistent
      acetabular dysplasia. The treatment of children who are of ambulatory age with
      developmental dysplasia of the hip using open reduction and combined osteotomies
      was safe and effective.

PMID- 9520894
TI  - Anatomic considerations of superior cluneal nerve at posterior iliac crest
      region.
AB  - No previous studies describe the anatomic relationship of the superior cluneal
      nerve to the posterior iliac crest and thoracolumbar fascia. In the current
      study, 15 cadavers were dissected to determine the relationship of the superior
      cluneal nerve to the posterior iliac crest and thoracolumbar fascia. The
      distances from the medial branch of the superior cluneal nerve to the posterior
      superior iliac crest and the midline were 64.7 +/- 5.3 mm and 81.0 +/- 9.2 mm,
      respectively. The distances between the level of the iliac crest and perforating
      points of the superior cluneal nerve on the thoracolumbar fascia were 5.8 +/- 1.8
      mm inferiorly for the medial branch, 2.2 +/- 1.8 mm superiorly for the
      intermediate branch, and 12.0 +/- 4.4 mm superiorly for the lateral branch,
      respectively. The proximal dissection above the perforating point of the nerve
      showed that the medial branch of the superior cluneal nerve is confined within a
      tunnel consisting of the thoracolumbar fascia and the superior rim of the iliac
      crest as it passes over the iliac crest. The intermediate and lateral branches of
      the superior cluneal nerve either pierce the thoracolumbar fascia or pass through
      an orifice or fissure in the thoracolumbar fascia. In two specimens, the medial
      branches of the superior cluneal nerve were constricted within the osteofibrous
      tunnel. The nerve was entrapped between the rigid fibers of the thoracolumbar
      fascia and the iliac crest.

PMID- 9520895
TI  - Blood flow measurement during distraction osteogenesis.
AB  - The regional blood flow of 30 distraction segments in 27 patients was measured
      during distraction osteogenesis. There were three groups of patients. Group A
      consisted of seven patients with high grade malignant tumors who received
      chemotherapy preoperatively and postoperatively. Group B consisted of eight
      patients with low grade malignant and aggressive benign tumors, who all were
      treated without chemotherapy. Group C (the control group) consisted of 12
      patients with nontumoral conditions. Using quantitative technetium scintigraphy,
      the regional blood flow within the distracted segment and surrounding soft
      tissues was measured. The measured radioisotope count was expressed as the ratio
      of the distracted site to the control site (blood flow ratio). The blood flow
      ratio for all the cases averaged 1.70 +/- 0.70. Group A had a lower blood flow
      ratio, which was statistically significant in comparison with the other two
      groups. The external fixation index showed no significant difference in callus
      formation among these three groups. No correlation was found between the blood
      flow ratio and external fixation index. Chemotherapy decreases regional blood
      flow, but with distraction osteogenesis the regional blood flow can be kept
      within the normal range or higher. Distraction osteogenesis may overcome the
      effects of chemotherapy by increasing blood flow.

PMID- 9520897
TI  - Visualization of bacterial glycocalyx with a scanning electron microscope.
AB  - Using a new technique for scanning electron microscopic preparation, bacterial
      glycocalyx is seen in its natural, highly hydrated state for the first time.
      Visual images of the glycocalyx obtained from these preparations are a marked
      departure from the visual images of glycocalyx obtained previously with
      conventional scanning electron microscopic analysis. The dominating presence of
      glycocalyx visualized in its naturally hydrated state gives credence to the role
      of bacterial glycocalyx as a mechanical barrier to host defenses and antibiotics
      and supports the role of glycocalyx as a significant factor in bacterial
      virulence.

PMID- 9520896
TI  - Implantation of a 16-channel functional electrical stimulation walking system.
AB  - A 16-channel electrical stimulation system was implanted in a 39-year-old patient
      with T10 paraplegia to restore sit to stand, walking, and exercise functions.
      System implantation required two surgical sessions. In the first session, the
      posterior muscle set consisting of bilateral semimembranosus, adductor magnus,
      and gluteus maximus muscles were exposed and epimysial electrodes sutured at the
      point of greatest muscle contraction. Closed double helix intramuscular
      electrodes were implanted in the erector spinae. Two weeks later, epimysial
      electrodes were attached to the eight anterior muscles consisting of the tibialis
      anterior, sartorius, tensor fasciae latae, and vastus lateralis with all 16
      electrode leads passed to the anterior abdominal wall. The electrodes were
      connected to two eight-channel stimulators placed in the iliac fossae, and the
      system was checked by activating the individual muscles. The implanted
      stimulators received stimulation instructions and power via a radio frequency
      link to an external control. Stimulation patterns for standing, walking, sitting,
      and exercise functions were chosen from a preprogrammed menu via a finger key
      pad. After 3 weeks of restricted patient activity, all electrodes stimulated
      either the target muscle or had an acceptable spillover pattern. The patient is
      undergoing a 16-week rehabilitation course of stimulated exercises gradually
      increasing in intensity. At the conclusion, the goal is to discharge the patient
      with the system for spontaneous use. Although long term followup is required to
      determine system reliability, preliminary clinical results indicate that
      targeted, repeatable, functional muscle contractions in the lower extremity can
      be achieved with a system consisting of epimysial electrodes.

PMID- 9520899
TI  - Cementless implant composition and femoral stress. A finite element analysis.
AB  - Proximal atrophy and thigh pain are recognized problems with some cementless
      femoral stems in total hip arthroplasty. It is thought that reduced femoral
      stress from alterations in load transfer caused by an intramedullary stem
      contributes to proximal femoral atrophy. An increase in flexural rigidity and
      bone stress near the stem tip is thought to contribute to thigh pain. A three
      dimensional finite element analysis study was performed to calculate stresses in
      the proximal femur and bone near the stem tip before and after implantation of a
      collared, proximally coated, cementless femoral prosthesis. The influence of
      prosthetic material was examined by changing implant composition from cobalt
      chrome to titanium alloy and leaving all other parameters constant. Femoral
      stress was increased twofold immediately below the collar with the titanium
      implant compared with the cobalt chrome. However, the proximal femoral stress in
      the titanium implanted model was still 1/10 that in the corresponding region of
      the unimplanted femur model. At the stem tip, as much as a 30% reduction in
      femoral stress was seen with the titanium stem compared with the cobalt chrome.
      These findings suggest biomechanical evidence of an advantage for titanium as an
      implant material compared with cobalt chrome for cementless femoral stems.

PMID- 9520898
TI  - Hydrogen peroxide inhibits giant cell tumor and osteoblast metabolism in vitro.
AB  - This study investigates the efficacy of using hydrogen peroxide as adjuvant
      therapy after extended local curettage for benign giant cell tumors of bone.
      Hydrogen peroxide is used clinically as a chemical adjuvant for removal of
      residual tumor cells, presumably by effervescent cleansing with minimal damage to
      surrounding soft tissue and bone cells. This investigation examined the effects
      of hydrogen peroxide on giant cell tumor cells and osteoblasts grown in culture.
      Fresh fragments of histologically confirmed giant cell tumor tissue (six
      patients) and trabecular bone (one patient) were excised. Cells obtained from the
      fragments were grown in culture. Confluent cell cultures were exposed to saline
      (control) or hydrogen peroxide (0.1-1000 mm) for 2 minutes, and incubation was
      continued for 12, 24, or 48 hours without hydrogen peroxide. Protein content,
      deoxyribonucleic acid content, tartrate resistant acid phosphatase activity, and
      alkaline phosphatase activity were measured in the cell layers. The medium from
      the final 12 hours of each incubation period was used to evaluate lactate
      production. Cell lysis or death occurred after exposing giant cell tumor cells
      and osteoblasts to 100 mm and 30 mm hydrogen peroxide, respectively,
      concentrations substantially lower than the 3% (880 mm) hydrogen peroxide
      commonly used clinically. These results support the theory of using a minimal
      concentration of hydrogen peroxide as a chemical adjuvant in the surgical
      treatment of giant cell tumors of bone.

PMID- 9520900
TI  - Pain and weakness of the shoulder in a 16-year-old boy.

PMID- 9520901
TI  - Magnetic resonance imaging of the musculoskeletal system. Part 9. Primary Tumors.
AB  - Magnetic resonance imaging, because of its exquisite soft tissue contrast, has
      dramatically improved the ability to preoperatively stage primary osseous and
      soft tissue neoplasms. This technique also has allowed the monitoring of the
      effects of chemotherapy and the screening for recurrence of neoplasms. The role
      of magnetic resonance imaging in the preoperative evaluation of the patient with
      a suspected primary osseous or soft tissue neoplasm is outlined, instances where
      magnetic resonance imaging potentially may make a specific diagnosis are
      outlined, the importance of gadolinium enhancement as an adjunct to native
      magnetic resonance imaging is stressed, and an algorithm for followup of patients
      after chemotherapy or definitive surgical treatment is presented. In all cases,
      the magnetic resonance images should be correlated with the plain film, which is
      still an important aspect of the diagnosis of osseous lesions.

PMID- 9520902
TI  - Hantavirus infection.

PMID- 9520903
TI  - Age-dependent accumulation of dolichol in rat liver: is tissue dolichol a
      biomarker of aging?
AB  - Dolichols are long hydrophobic molecules broadly distributed in all tissues and
      cellular membranes of eukariotic cells. Dolichol affects membrane structure and
      fluidity, membrane-associated protein activities, and membrane sensitivity to
      oxidative stress. Reports have shown that dolichols exhibit a remarkable (6- to
      30-fold) age-related increase in the tissues of adult and mature rats and of old
      flies, mice, and humans. In our longitudinal study, the age-related accumulation
      of dolichol was monitored in the liver tissue of male Sprague Dawley rats fed ad
      libitum up to age of 27 months. In addition 24-month-old rats subjected to
      different regimens of anti-aging diet restriction (40% calorie restriction or
      every-other-day feeding ad libitum) were tested. A parallel study of the
      accumulation of carbonyl in liver protein (a proposed biomarker of aging) was
      made. In addition, the age-related decline of liver autophagy/proteolysis was
      studied in isolated liver cells, in view of the essential role of this function
      in liver membrane maintenance. Results show that an age-dependent accumulation of
      dolichol can be observed in the liver of the rats fed ad libitum but not in the
      liver of 24-month-old food-restricted rats, that accumulation of dolichol
      precedes the accumulation of altered liver proteins, and that dolichol
      accumulation is accompanied by a decline in liver autophagy. It is concluded that
      dolichol accumulation satisfies the proposed primary and secondary applicable
      criteria and the desirable features required to be qualified as a biomarker of
      aging.

PMID- 9520904
TI  - Protein glycation in the aging male Sprague-Dawley rat: effects of antiaging diet
      restrictions.
AB  - Protein glycation and accumulation of advanced glycosylated end-products (AGEs)
      are supposed to play an important role in the process of aging. Dietary
      restriction increases life span and delays the onset of most age-associated
      diseases. Age-dependent changes in glucose homeostasis and glycated plasma
      proteins and hemoglobin were determined, and AGEs formation was measured as
      fluorescence in skin and aortic collagens in male Sprague-Dawley rats fed ad
      libitum or subjected to every-other-day feeding or 40% food restriction. In aging
      control rats, skin and aortic collagen-linked fluorescence increased with a
      similar exponential curve (aortic value being always higher), whereas glycated
      plasma protein and hemoglobin decreased slightly. Dietary restrictions decreased
      glycated plasma proteins and fluorescent products in skin collagen of younger but
      not older rats, and did not affect glycated hemoglobin or aortic collagen
      fluorescence. In conclusion, our data indicate that age-related changes in
      glucose homeostasis do not play a substantial role in aging; and collagen-linked
      fluorescence increases significantly during aging, but it may not be sensitive to
      dietary intervention.

PMID- 9520905
TI  - Changes in hepatic DNA binding proteins as a function of age in rats.
AB  - The process of aging is accompanied by many changes in gene expression, occurring
      in virtually all organs of the affected individual. Here we report on the
      relative changes in DNA binding activity of a panel of 15 different transcription
      factors in the liver of adult (15-month-old) and old (25-month-old) Sprague
      Dawley rats. When expressed as a function of nuclear protein concentration, a
      great majority of the transcription factors analyzed do not show significant
      differences in DNA binding activities as a function of age, except activator
      protein 1 (AP-1) and nuclear factor-kappa B, both of which show increased
      activities in the older animals, and hepatocyte nuclear factor-3, which undergoes
      a switch from predominantly alpha and beta subspecies in the adults, to
      predominantly gamma subspecies in the old animals. Further examination of some of
      the members of the AP-1 complex using Western blot analysis indicates that the
      increase in binding activity of this particular complex might be due to an
      increase in the relative mass of Jun B, presumably resulting in a switch from
      predominantly c-Fos/Jun D in the young to c-Fos/Jun B complexes in the old
      animals. Nuclear extracts prepared from the liver of old animals yield less
      proteins per mass of DNA than similar extracts prepared from younger animals.
      Accordingly, if the data are analyzed as a function of genomic DNA, our results
      indicate that aging results in a consistent, but generally not statistically
      significant decrease in most transcription factor DNA binding activities, with AP
      1, nuclear factor-kappa B, and transcription factor II D being the exception to
      this decline.

PMID- 9520907
TI  - Growth hormone in postmenopausal women after long-term oral estrogen replacement
      therapy.
AB  - Studies of estrogen effects on growth hormone (GH) and its pulsatile release in
      postmenopausal women have typically utilized estrogen replacement therapy (ERT)
      of relatively short duration (days to weeks). The purpose of this study was to
      compare GH measures from healthy postmenopausal women who were on oral ERT for 3
      years or more (n = 24; mean ERT duration = 16.1 years) with women not on ERT
      (NERT; n = 40). Blood samples were drawn remotely every 20 min for 24 h and then
      analyzed for mean 24-h GH, mean GH during sleep, and mean 24-h insulin-like
      growth factor-I (IGF-I). GH peak analyses were also performed. Mean 24-h GH and
      GH during sleep were significantly higher and IGF-I was significantly lower in
      ERT women compared with NERT women. In addition, use of long-term ERT was
      associated with more GH peaks relative to women not on ERT, but no change in GH
      peak amplitude or area. GH was not related to age in either group. GH was
      strongly and negatively correlated with measures of adiposity in NERT women but
      not in ERT women. In conclusion, long-term oral ERT is associated with increased
      circulating GH and decreased IGF-I levels, even after many years of treatment.

PMID- 9520906
TI  - Reduced DNA synthesis in primary cultures of hepatocytes from old mice is
      restored by thymus grafts.
AB  - We previously observed in vivo that a neonatal thymus grafted into old mice can
      correct age-related changes such as occurrence of hepatocyte tetraploid nuclei
      and impaired isoproterenol-induced DNA synthesis in submandibular glands. The aim
      of the present paper was to study the influence of age and thymus on basal and
      beta-adrenergic-stimulated DNA synthesis using primary cultures of mouse
      hepatocytes. In the absence of any adrenergic agents, cells from young mice show
      peak DNA synthesis between 36 and 48 h; old mice show a similar time course, but
      the peak is significantly reduced statistically. The main result is represented
      by the behavior of hepatocytes from old thymus-grafted mice, which recover the
      levels of [3H]-thymidine incorporation toward young-like values. Grafted animals
      also show a correction of total DNA content that is increased in old mice. The
      addition of isoproterenol does not modify the DNA synthetic pattern, whereas the
      antagonist propranolol causes a slight but statistically significant decrease.

PMID- 9520908
TI  - Increased total 7 alpha-hydroxy-dehydroepiandrosterone in serum of patients with
      Alzheimer's disease.
AB  - Evidence has indicated that circulating adrenal steroid quantitites were
      significantly changed in patients with Alzheimer's disease (AD). Aside of 3 beta
      sulfatation and 3 beta-acylations, levels of dehydroepiandrosterone (DHEA) result
      from production and metabolic transformation yields. 7 alpha-Hydroxylation of
      DHEA has been described in humans, and 7 alpha-hydroxy-DHEA may be responsible
      for the known antiglucocorticoid effects of DHEA. Using a negative ion
      fragmentometry method with gas chromatography/mass spectrometry on
      trifluoroacetate derivatives, we measured levels of free 7 alpha-hydroxy-DHEA as
      well as its sulfated conjugate and its fatty acid esters in serum of 10 female
      patients with AD and of 8 age-matched healthy control women. Free 7 alpha-hydroxy
      DHEA levels in AD and controls were not significantly different (240.2 +/- 37.2
      pg/ml and 206.8 +/- 21.6 pg/ml, respectively), but sulfate conjugate levels were
      significantly increased in AD (p = .01) (262 +/- 28.4 and 145.4 +/- 27.6,
      respectively) as well as fatty acid esters (p = .041) (65.7 +/- 6.9 and 40.7 +/-
      9.2, respectively). These results indicated that the total 7 alpha-hydroxy-DHEA
      produced was significantly increased in AD (p = .024) and may contribute to the
      disease-related disturbances of DHEA production and metabolism.

PMID- 9520909
TI  - Comparison of the postprandial plasma vitamin A response in young and older
      adults.
AB  - To assess the influence of age on vitamin A intestinal and liver metabolism in
      humans, the postprandial plasma concentrations of intestinal-originated vitamin
      A, i.e., retinyl esters, and liver-originated vitamin A, i.e., retinol, were
      compared in eight young (20-30 years old) and eight elderly (64-72 years old)
      healthy men. Plasma and chylomicron retinyl esters and retinol concentrations
      were measured for up to 24 h following the intake of a test meal that contained
      23,300 RE retinyl palmitate. The chylomicron retinyl palmitate response (area
      under the curve) was not significantly different between the two groups, but its
      peak was slightly delayed (1 h) in the elderly men. The proportion of the
      different retinyl esters secreted in the chylomicrons was not significantly
      different between the two groups. The postprandial plasma retinol concentration
      did not change in the young participants, whereas it significantly increased in
      the elderly. These results suggest that vitamin A intestinal absorption and
      retinol intestinal esterification processes are not markedly modified in the
      elderly, whereas the chylomicron clearance and the regulation of postprandial
      plasma retinol concentration are apparently altered in these subjects.

PMID- 9520911
TI  - Selection for longevity confers resistance to low-temperature stress in
      Drosophila melanogaster.
AB  - One theory of the evolution of longevity says that improvement in life span is
      dependent on an increased ability to resist environmental stresses of all kind.
      Selective breeding of Drosophila melanogaster populations for longevity has
      demonstrably increased life span and also altered a number of other traits, such
      as resistance to starvation, desiccation, and ethanol fumes, and the ability to
      sustain longer flight. While the exact physiologic basis of some of these traits
      is not yet fully understood, at least some are known to derive from the
      properties of metabolic substrates of glycolysis. Improvement in those characters
      can depend partially, therefore, on altered stores of metabolites created from
      glycogen. Based on the known general relationship of some traits and the
      suspected basis in metabolism of others, we examine the possibility here that
      increased life span is accompanied by other traits that also confer physiologic
      resistance to stress. Specifically, we test the prediction that long-lived
      populations of fruit flies should be more resistant to low (prefreezing) and
      freezing temperature extremes. Both selected and control populations were found
      to be susceptible to prefreezing (1.5 degrees C) and freezing temperatures (0
      degree C) here, but adults and pupae of the long-lived populations generally
      survived better in both situations, and at all durations of exposure. The
      resistance of individuals improved with acclimatization, but was superior in the
      long-lived populations whether thermal decline was rapid or stepwise. Cold
      resistant, long-lived populations also had significantly higher in vitro levels
      of glycerol, a cryoprotectant metabolite produced from glycogen. However, while
      adults and pupae of long-lived stocks were more resistant to cold, larvae of
      those stocks were more sensitive and survived relatively poorly at every length
      of exposure and acclimation. This surprising result implies that larvae maintain
      lower levels of cryoprotectant substances. Upon becoming pupae, however, stage
      specific capabilities for environmental resistance and long life emerge. This
      conclusion agrees with a prior study of these stocks indicating that the uptake
      and use of nutrients in developing larvae are restricted in long-lived
      populations.

PMID- 9520910
TI  - The effect of age-dependent increase in fat mass on peripheral insulin action is
      saturable.
AB  - Insulin resistance and increased fat mass (FM) are common in human aging. We
      aimed to investigate the relationship between the age-dependent increase in FM
      and insulin resistance (by euglycemic hyperinsulinemic clamp technique), in a
      homogenous rodent model. The decline in insulin responsiveness was linear until
      late adulthood when body weight, FM, and epididymal fat reached a critical amount
      (r > .750, for all). Above this critical point, there was no further decline in
      insulin responsiveness with aging and with increased BW (p < .00001 for all
      spline curve analyses). This decline in insulin-mediated glucose uptake was
      accounted for by a decrease in whole body glycolytic rate with no change in the
      rate of glycogen synthesis. Thus, in this homogenous model, an early increase in
      FM is associated with impairment in insulin action until a critical FM is
      achieved, after which there is no additional insulin resistance with aging. We
      suggest that decreasing insulin responsiveness, in a heterogeneous group such as
      humans, will only occur within a specific accretion of visceral or total FM.

PMID- 9520912
TI  - Is malnutrition overdiagnosed in older hospitalized patients? Association between
      the soluble interleukin-2 receptor and serum markers of malnutrition.
AB  - BACKGROUND: Many researchers have speculated that markers of malnutrition such as
      albumin, prealbumin, cholesterol, and transferrin are influenced by inflammation.
      The mechanism of this interaction has not been well understood. METHODS: This was
      a prospective cross-sectional study. We evaluated 72 male patients older than 60
      years admitted to a geriatric rehabilitation unit. Subjects with severe hepatic
      or renal diseases were excluded. We measured body mass index, caloric intake,
      serum albumin, prealbumin, cholesterol, transferrin, hemoglobin, and total
      lymphocyte count. To detect inflammation, we measured C-reactive protein,
      Westergren sedimentation rate, fibrinogen, and cytokines including tumor necrosis
      factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), IL-6, IL-2, and the
      soluble IL-2 receptor. RESULTS: Soluble IL-2 receptor was negatively associated
      with albumin (r = -.479, p < .0001), prealbumin (r = -.520, p = < .0001),
      cholesterol (r = -.487, p = .0001), transferrin (r = -.455, p = .0002), and
      hemoglobin (r = -.371, p = .002). TNF-alpha, IL-1 beta, IL-6, and IL-2 were not
      associated with these measures. CONCLUSIONS: Inflammation increases the incidence
      of hypoalbuminemia and hypocholesterolemia, potentially leading to overdiagnosis
      of malnutrition. We suggest that albumin, cholesterol, prealbumin, and
      transferrin be used with caution when assessing the nutritional status of older
      hospitalized patients. In the future, soluble IL-2 receptor levels might be used
      to correct for the impact of inflammation on these markers of malnutrition.

PMID- 9520913
TI  - The effect of adenosine on the reduced heart rate response to exercise in the
      elderly.
AB  - BACKGROUND: In a previous study we demonstrated that excessive endogenous
      adenosine production and/or response was responsible for the blunted tachycardia
      to bolus intravenous doses of isoproterenol in the elderly. In this study, we
      tested the hypothesis that excessive endogenous adenosine may also be responsible
      for the diminished maximal tachycardia with aging. METHODS: Twelve young (mean
      age 27.3 +/- .61 yr) and 12 older (mean age 66.8 +/- .9 yr) healthy men were
      asked to perform maximum exercise tests in the presence of placebo or
      theophylline at plasma concentrations between 15-20 micrograms/ml. Heart rate,
      oxygen consumption, and respiratory gas exchange ratio were continuously
      monitored and recorded during the exercise. In addition, plasma lactate,
      glycerol, renin activity, and catecholamines were measured before and after
      maximal exercise. RESULTS: Maximum heart rate to exercise was higher in the young
      (190 +/- 3 bpm in the young, 157 +/- 2 bpm in the old) and increased by 4.5 +/-
      1.2 bpm in the young and 9.8 +/- 2.6 bpm in the old with the administration of
      theophylline that resulted in an equivalent serum concentration in the two age
      groups. This age difference in the increase was not significant but approached
      significance at a p value of .07. Maximum VO2 was also greater in the young group
      and this was unaffected in both groups by theophylline administration. The
      increase in serum lactate and plasma renin activity (PRA) to exercise was higher
      in the young group both in the presence and absence of theophylline. CONCLUSIONS:
      Our data could not identify excessive adenosine in the older group as the cause
      of diminished maximal exercise heart rate with aging. It is likely that the
      diminished chronotropic response to exercise in the older humans is due to a
      mechanism intrinsic to the cardiac excitatory tissue.

PMID- 9520914
TI  - Clinical detection of depression among community-based elderly people with self
      reported symptoms of depression.
AB  - BACKGROUND: Depression is under-diagnosed and under-treated in the primary care
      sector. The purpose of this study was to determine the association between self
      reported indications of depression by community-dwelling elderly enrollees in a
      managed care organization and clinical detection of depression by primary care
      clinicians. METHODS: This was a 2-year cohort study of elderly people (n = 3410)
      who responded to the Geriatric Depression Scale (GDS) at the midpoint of the
      study period. A broad measure of clinical detection was used consisting of one or
      more of three indicators: diagnosis of depression, visit to a mental health
      specialist, or antidepressant medication treatment. RESULTS: Approximately half
      of the community-based elderly people with self-reported indications of
      depression (GDS > or = 11) did not have documentation of clinical detection of
      depression by health providers. Physician recognition of depression tended to
      increase with the severity of enrollees' self-reported feelings of depression.
      Men 65-74 years old and those > or = 85 years old were at highest risk for under
      detection of depression by primary care providers. CONCLUSIONS: Clinical
      detection of depression of elderly people living in the community continues to be
      a problem. The implications of failure to recognize the possibility of depression
      among elderly White men suggest a serious public health problem.

PMID- 9520915
TI  - Impact of chronic diseases on functional limitations in elderly Chinese aged 70
      years and over: a cross-sectional and longitudinal survey.
AB  - OBJECTIVE: To examine the association of some common medical conditions with
      functional limitation in elderly Chinese aged 70 years and over, to estimate the
      percentage of disability attributable to individual diseases, and to attempt to
      identify predisposing factors by documenting the development of functional
      limitation over an 18-month period in those subjects with a particular disease
      who were independent initially. SUBJECTS AND METHODS: The cross-sectional data
      set consisted of 2,032 (999 M, 1,033 F) subjects aged 70 years and over recruited
      by random sampling (stratified by age and sex) of all recipients of old-age and
      disability allowance, which covers over 90% of the elderly population.
      Information regarding medical condition and functional assessment of ten basic
      activities of daily living using the Barthel Index were obtained by personal
      interviews and physical assessment of the respondents at their places of
      residence. The longitudinal data set consisted of 1,334 subjects with no
      functional limitation at baseline who were alive after 18 months. Functional
      status was reassessed. RESULTS: After adjusting for age and sex, diseases
      associated with severe functional limitation (Barthel Index < 15) were dementia,
      stroke, Parkinson's disease, and fractures. Those associated with mild to
      moderate functional limitation (Barthel Index 15-19) were the same, with the
      addition of asthma and diabetes mellitus. The attributable fraction for severe
      limitation was highest for stroke, dementia, and fractures. Stroke and arthritis
      were identified as diseases predisposing to mild to moderate functional
      limitation over an 18-month period among those subjects who were independent
      initially. CONCLUSION: Stroke, dementia, and fractures were the main chronic
      diseases associated with severe functional limitation in elderly Hong Kong
      Chinese. Attempts to reduce the disability burden in this population should
      target these diseases.

PMID- 9520916
TI  - Differing characteristics of hepatitis B and C risk factors among elders in a
      rural area in Taiwan.
AB  - BACKGROUND: Both hepatitis B and C are major health concerns in Taiwan. The goal
      of this study was to determine how risk factors for hepatitis B and C differed in
      this study population. It was also hoped that the data might help determine how
      age and place of residence affect hepatitis risk factors. METHODS: Complete serum
      and hepatitis marker analysis (HBsAg and AntiHCV) was done for 282 individuals
      over 65 years old. Of these, 254 were interviewed for risk factor analysis.
      RESULTS: Of the 282 subjects, 8.2% were HBsAg+, 27.3% were AntiHCV+, and 3.2%
      were both HBsAg+ and AntiHCV+. AntiHCV+ subjects were more likely than AntiHCV
      subjects to have had frequent medical injections, odds ratio (OR) = 2.94, 95%
      confidence interval (CI) (1.68, 5.12), and it was the only independent risk
      factor for determining AntiHCV+, OR = 3.26, 95% CI (1.85, 6.11) (N = 254). The
      AntiHCV+ group had higher alanine and asparate aminotransferase levels but lower
      cholesterol and triglyceride levels than AntiHCV- and HBsAg+ groups (p < .0001).
      Abnormal ALT existed in 40.3% of AntiHCV+ and 10.7% of AntiHCV- cases. ALT was
      associated with AntiHCV and sex, although abnormal AST was only associated with
      AntiHCV. CONCLUSIONS: AntiHCV was closely related with frequent medical
      injections and was the primary risk factor for abnormal ALT and AST levels in
      this study population. It appears that frequent medical injections are an
      important risk factor because of the previously common habit of reusing syringes.
      This is of major concern to elders in Taiwan because of their much greater
      likelihood of repeated exposure.

PMID- 9520918
TI  - Soleus H-reflex gain in elderly and young adults: modulation due to body
      position.
AB  - BACKGROUND: The control of posture and balance in the elderly is a primary health
      concern. Postural instability directly leads to a greater incidence of falling in
      the elderly population. One important neuromuscular mechanism instrumental in the
      control of posture and balance is the reflex system. The purpose of this study
      was to examine the gain of the soleus H-reflex in young and elderly adults in two
      different body positions: standing and prone. METHODS: Eighteen neurologically
      healthy volunteers were categorized by age in two groups: young (n = 9, mean age
      = 23.3 yr) and elderly (n = 9, mean age = 71.7 yr). In each position, the resting
      H-max/M-max ratio was determined. The gain of the reflex was also assessed by
      instructing the subject to perform voluntary contractions of 10, 20 and 30% of
      their maximum voluntary contraction, using real-time EMG biofeedback. Data were
      sampled on-line using custom designed software (sample rate = 2 kHz). Dependent
      variables included the average background EMG of the soleus muscle (40 ms window
      prior to stimulation) and the peak-to-peak amplitude of the elicited soleus H
      reflex. To examine the gain of the reflex, the peak-to-peak amplitude of the H
      reflex was plotted against the background EMG activity for each contraction
      intensity. RESULTS: Results indicated the following: young subjects significantly
      depressed the H-max/M-max ratio when standing (69.3% prone, 55.1% standing),
      whereas elderly subjects increased the ratio (36.1% prone, 54.5% standing). Also,
      the young subjects modulated the gain of the reflex from prone to standing (3.30
      prone, 3.68 standing), and the elderly subjects demonstrated no gain modulation
      in the different body positions (2.23 prone, 1.91 standing). In both body
      positions the young subjects demonstrated significantly higher gain that the
      elderly subjects. CONCLUSIONS: The results demonstrate different control
      strategies for young and elderly subjects between prone and standing body
      positions.

PMID- 9520917
TI  - The effect of falls and fall injuries on functioning in community-dwelling older
      persons.
AB  - BACKGROUND: Several preventive strategies have proven effective at reducing the
      occurrence and rate of falling. It remains to be determined, however, whether,
      and to what extent, falls and/or fall injuries are independent determinants of
      adverse functional outcomes in older persons. METHODS: A probability sample of
      1,103 community-dwelling persons over age 71 years was followed for 3 years. The
      957 cohort members (87%) who participated in at least one follow-up interview
      while residing in the community were included in this study. Outcome measures
      included one and three year change in basic and instrumental activities of daily
      living (BADLs-IADLs), social activities, and physical activities. Based on daily
      calendars and hospital surveillance, participants were placed into one of four
      levels of fall status: no falls, one fall without serious injury, at least two
      falls without serious injury, and one or more falls with serious injury.
      Hierarchical linear regression models, sequentially adding six domains of
      covariates, were constructed to examine fall status as a risk factor for change
      in function. RESULTS: One noninjurious fall (beta = -.437; p < .01), at least two
      noninjurious falls (beta = -.877; p < .001); and at least one injurious fall
      (beta = -1.254; p < .001) were each associated with decline in BADL-IADL function
      over 3 years after adjusting for covariates (model R2 = .2617). Experiencing two
      or more noninjurious falls (beta = -.538; p < .05) was associated with decline in
      social activities (model R2 = .2779) while experiencing at least one injurious
      fall (beta = -.580; p < .01) was associated with decline in physical activity
      (model R2 = .4231). CONCLUSIONS: Falls and fall injuries appear to be independent
      determinants of functional decline in community-dwelling older persons. Falling
      is a health condition meeting all criteria for prevention: high frequency,
      evidence of preventability, and high burden of morbidity.

PMID- 9520920
TI  - Differentiating drivers with dementia of the Alzheimer type from healthy older
      persons with a Traffic Sign Naming test.
AB  - BACKGROUND: Dementia may contribute significantly to the driving impairment
      commonly associated with older adults. A brief, reliable, and sensitive screening
      method to identify drivers who may have cognitive impairment due to Alzheimer's
      disease or other dementing illnesses is needed for a variety of settings,
      including driver's license renewal offices. METHODS: Control and demented
      individuals who participated in the Washington University Alzheimer's Disease
      Research Center (ADRC) between March 1, 1995, and November 30, 1995, were
      evaluated for the ability to identify traffic signs correctly. After initially
      testing 39 traffic signs, 10 signs were selected based on scorer reliability and
      their ability to discriminate cognitively normal individuals from those with
      dementia. RESULTS: Sixty-six cognitively normal older people (average age 78
      years) and 70 people with dementia (average age 76 years) were tested. Using a
      cutoff score at or below 9 (out of a possible score of 20), the Traffic Sign
      Naming test successfully identifies 74% of people with mild or moderate dementia
      of the Alzheimer type (DAT) from cognitively healthy older persons of comparable
      age, sex, education, and socioeconomic status; 11% of the healthy drivers were
      misclassified as demented. CONCLUSIONS: A brief, 2-min or less, easily
      administered naming test of 10 traffic signs differentiated drivers with mild or
      moderate DAT from cognitively normal controls. This brief test may be useful to
      identify older drivers in need of further assessment of driving skill.

PMID- 9520919
TI  - Dynamic stability in elders: momentum control in locomotor ADL.
AB  - BACKGROUND: Momentum must be controlled in stable locomotor activities, including
      sit-to-stand and gait. The relationship of momentum control and balance
      maintenance in elders or in a balance-impaired population has not been studied.
      Although decreased locomotor speed has long been reported among elders, the
      literature is lacunar concerning the mechanical mechanisms underlying this
      slowing. The purpose of this study was to describe the whole body and upper body
      linear and angular momentum for healthy elders during sit-to-stand and gait and
      compare them to a group of balance-impaired elders who have bilateral vestibular
      hypofunction (BVH). METHODS: Ten elders with BVH were matched to 10 healthy
      elders aged 67-90. Linear and angular momentum were calculated for sit-to-stand
      and for free speed and paced gait. Means and 95% confidence intervals were used
      to compare groups. RESULTS: Elders with BVH used significantly less linear and
      angular momentum to rise from a chair than healthy elders and showed excessive
      lateral momentum during gait, despite walking at a slower velocity. CONCLUSIONS:
      Healthy elders limit momentum generation by decreasing gait velocity, apparently
      because they lack sufficient strength or balance control to safely dissipate the
      momentum that a faster, less controlled gait engenders. Elders with BVH further
      limit momentum in locomotor activities to decrease their risk of falling, but are
      apparently unable to control lateral momentum during gait. Excessive lateral
      momentum in gait among balance-impaired elders leads to loss of balance, a
      frequent occurrence in this patient population.

PMID- 9520921
TI  - Correlation between two clinical balance measures in older adults: functional
      mobility and sensory organization test.
AB  - BACKGROUND: Functional mobility of older adults has been shown to correlate with
      stance stability to various extents. This variability could be due to the
      difference in the way sensory information is processed in these two types of
      balance tests. Correlations between functional mobility and stance stability
      under altered sensory conditions, such as those in the Sensory Organization Test
      (SOT), are needed to test this possibility. The present study investigated the
      correlation between the performance of older adults on a newly developed Sensory
      Oriented Mobility Assessment Instrument (SOMAI) and on the various sensory
      conditions of the SOT. METHODS: Twenty-seven community-dwelling older adults (76
      +/- 7 years) underwent tests of the six SOT conditions and 10 SOMAI mobility
      maneuvers performed under normal- and focal-vision (peripheral vision eliminated)
      conditions. Behavioral performance in the two SOMAI conditions and the amounts of
      postural sway in the six SOT conditions were ranked among the subjects.
      Correlations of performance rankings on these two tests were analyzed. RESULTS:
      Performance on the two SOMAI conditions significantly correlated with that on the
      SOT conditions in which accurate visual, vestibular, and somatosensory inputs
      were all present (p < .05). Performance on the focal-vision SOMAI condition was
      also significantly correlated with that on the SOT condition in which
      somatosensory input was unreliable for orientation while visual and vestibular
      inputs were reliable (p < .05). There were no correlations between the SOMAI
      performance and performance on the no-vision or unreliable-vision SOT conditions.
      CONCLUSIONS: The ability to use all visual, somatosensory, and vestibular inputs
      for balance was correlated with functional mobility. The moderate correlations
      between the performance on the normal-sensory SOT condition and the SOMAI
      conditions suggest that body systems other than balance senses also contribute to
      mobility performance.

PMID- 9520923
TI  - The structure of depression among elderly institution residents: affective and
      somatic correlates of physical frailty.
AB  - BACKGROUND: Confounding of depression with somatic illness and anxiety, a problem
      in any age group, may be especially troublesome in frail older persons. This
      paper examined this problem in a factor analytic study of the structure of
      depressive symptomatology, identifying affective and somatic symptom clusters and
      relating those clusters to health and functional variables cross-sectionally and
      prospectively over a 1-year interval. METHODS: The factor structure of a DSM-IV
      symptom checklist was examined among 1,245 elderly long-term care residents.
      Regression analyses examined the association of resulting factors with cognition,
      functional disability, self- and physician-rated health, and pain at baseline and
      a year later. One-year mortality was also examined. RESULTS: Factor analysis
      revealed three unique symptom clusters: depressed mood, somatic symptoms, and
      psychic anxiety. Depressed mood and somatic symptoms were associated cross
      sectionally with all functional health variables, but psychic anxiety was
      associated only with pain. Longitudinally, depressed mood was the only
      independent predictor of decline in cognition, functional ability, physician
      rated health, and mortality; the last effect, however, did not withstand control
      for baseline health and functioning. Somatic symptoms at baseline predicted
      decrement in self-rated health a year later. Effects varied as a function of
      cognitive status. CONCLUSIONS: These data suggest that concerns about the
      confounding role of somatic symptoms in the association of depression with
      physical health are unfounded. Although somatic symptoms of depression and
      anxiety were associated with health and functional status cross-sectionally,
      depressed mood was by far the stronger predictor of health declines over time.

PMID- 9520922
TI  - The relation between morbidity and cognitive performance in a normal aging
      population.
AB  - BACKGROUND: Factors related to physical health have been implicated in both
      normal and pathological aging of cognitive abilities. To substantiate this
      notion, we studied existing morbidity, as diagnosed by the general practitioner
      according to well-defined criteria, as a potential predictor of cognitive test
      performance. METHODS: A sample of 1360 individuals, aged 24-81 years and living
      in the community, was stratified for age, sex, and general ability. Active and
      total morbidity in this group were classified according to the International
      Classification of Primary Care. Neurocognitive tests were used to assess the
      domains of verbal memory, sensorimotor speed, and cognitive flexibility. RESULTS:
      Multiple regression analyses with adjustment for age, sex, and educational level
      showed both insulin-dependent and noninsulin-dependent diabetes to be negatively
      associated with all cognitive measures. More specific negative associations were
      found for chronic bronchitis (performance speed) and presbyacusia (memory).
      Single or aggregated cardiovascular morbidity (including hypertension) was
      unrelated to test performance. CONCLUSIONS: Existing morbidity as a whole
      contributes only modestly (up to 3.5%) to total variance in cognitive function.
      However, some specific, relatively common diseases of the elderly, such as
      diabetes and chronic bronchitis, may aggravate the age-related decline in
      cognitive ability.

PMID- 9520924
TI  - Personality counts for a lot: predictors of mental and physical health of spouse
      caregivers in two disease groups.
AB  - The purpose of this study were to examine the influence of personality on mental
      and physical health of spouse caregivers and to determine whether there were
      differences in such influences depending on disease context. The disease contexts
      compared were Alzheimer's disease (AD) and Parkinson's disease (PD; with no
      coexisting dementia)--both chronic, degenerative diseases of later life. It was
      predicted that personality would be related to mental and physical health,
      directly and indirectly, and that AD caregivers would have higher levels of
      perceived stress and worse mental and physical health outcomes. Participants in
      the study were 175 caregivers (88 AD; 87 PD) living at home with their ill
      spouses. The data provided an excellent fit to the hypothesized model of the
      relationships between personality, disease group, social support, perceived
      stress, and mental and physical health. Seventy-eight percent of the variance in
      mental health was accounted for and 35% of the variance in physical health was
      explained. Personality had significant direct and indirect effects on mental
      health and significant indirect effects on physical health. As predicted, AD
      caregivers had significantly worse mental health than PD caregivers; however, AD
      caregivers had better physical health than PD caregivers, controlling for other
      variables in the model. These results are discussed in relation to the existing
      caregiving and behavioral medicine literature. Future research should include
      different domains of personality--states and longer term self-regulatory
      processes in addition to traits--to advance models of caregiving processes
      further.

PMID- 9520925
TI  - Patterns of intergenerational exchange and mental health.
AB  - Past research on intergenerational exchanges suggests that parents and adult
      children remain vitally involved in supportive exchanges in later life. What has
      not been examined is the long-term importance of patterns of intergenerational
      exchange for individual mental health and well-being. Using data drawn from the
      two waves of the National Survey of Families and Households on adults aged 50 and
      older (N = 2237, MAge = 62.3), we tested hypotheses derived from three
      theoretical explanations of the relationship between exchange patterns and
      psychological well-being. We found strong evidence for the importance of
      contingent exchanges between parents and adult children in promoting older
      adults' psychological well-being. Whereas receiving contingent exchange has
      positive consequences, noncontingent giving can have negative consequences around
      specific transitions in the lives of parents and children.

PMID- 9520926
TI  - The role of self-perceived usefulness and competence in the self-esteem of
      elderly adults: confirmatory factor analyses of the Bachman revision of
      Rosenberg's Self-Esteem Scale.
AB  - This article reports on a confirmatory analytic study of the Bachman Revision
      (1970) of Rosenberg's Self-Esteem Scale (1965) that was used in the Australian
      Longitudinal Study of Ageing (ALSA). Participants comprised 1,087 elderly people
      aged between 70 and 103 years (mean 77 years). Five competing factor models were
      tested with LISREL8. The best-fitting model was a nested one, with a General Self
      Esteem second-order factor and two first-order factors, Positive Self-regard and
      Usefulness/Competence. This model was validated with data from a later wave of
      ALSA. Usefulness and competence have received little attention in the
      gerontological literature to date. Preliminary results indicate that
      usefulness/competence may be an important predictor of well-being. Further work
      is required on the relationships among usefulness, competence, self-esteem, and
      well-being in elderly people.

PMID- 9520927
TI  - Age-biased interpretation of memory successes and failures in adulthood.
AB  - This study extends previous research, which has demonstrated that age stereotypes
      bias the interpretation of everyday memory failures, by examining the responses
      of 81 young and 84 old participants to questions about the meaning and causes of
      memory successes and failures. The scenarios used described memory situations in
      which age differences would be small or nonexistent and included situtional
      factors that could account for the memory outcome, providing a more stringent
      test of the age-bias hypothesis. Under such testing conditions, memory successes
      in old targets are seen to be less typical than for young targets. Moreover,
      memory failures are seen to be more strongly caused by lack of ability and viewed
      as more worrisome. Finally, memory outcomes, in general, are perceived to be less
      controllable for old targets.

PMID- 9520928
TI  - Associative learning and short-term forgetting as a function of age, perceptual
      speed, and central executive functioning.
AB  - In a study of two components of associative learning, it was found that during
      acquisition older people were more likely to forget material on which they were
      previously correct, but only for associations which were not well learned. Older
      people also formed fewer correct associations in the course of the task.
      Differences in learners' perceptual speed were found to account for some of the
      age deficit in the number of learning attempts, but speed was less relevant in
      accounting for age differences in forgetting and in the ability to generate new
      responses. Measured central executive functioning was less important in
      accounting for age differences on all measures. It is argued that forgetting is
      less important as a source of learning performance than has been suggested
      elsewhere (e.g., Salthouse, 1994). Rather, it is the inability of older persons
      to form associations as rapidly as younger ones which accounts for most of the
      age effect.

PMID- 9520929
TI  - Successful behavioral treatment for reported sleep problems in elderly caregivers
      of dementia patients: a controlled study.
AB  - Although sleep problems are common among dementia caregivers, there has been no
      research thus far describing treatment of such problems using behavioral
      techniques. In this study, 36 elderly dementia caregivers with disturbed sleep
      were randomly assigned to either a brief behavioral intervention or a wait list
      control. The active treatment consisted of standard sleep hygiene, stimulus
      control, and sleep compression strategies as well as education about community
      resources, stress management, and techniques to reduce patient disruptive
      behaviors. Caregivers in active treatment showed significant improvements in
      sleep at post-treatment and 3-month follow up. No significant differences between
      groups were observed for caregiver mood, burden, or patient behavior problems,
      suggesting that sleep improvements were not an artifact of depression treatment.
      Treatment responders tended to be younger and more compliant with treatment
      recommendations than non-responders. Results suggest that behavioral techniques
      may well be a viable alternative to medication for sleep problems in aging
      caregivers.

PMID- 9520930
TI  - Attention and driving performance in Alzheimer's disease.
AB  - The present study examined the relationship between visual attention measures and
      driving performance in healthy older adults and individuals with very mild and
      mild dementia of the Alzheimer type (DAT). Subjects were administered an on-road
      driving assessment and three visual attention tasks (visual search, visual
      monitoring, and useful field of view). The results indicated that error rate and
      reaction time during visual search were the best predictors of driving
      performance. Furthermore, visual search performance was predictive of driving
      performance above and beyond simple dementia severity and several traditional
      psychometric tests. The results suggest that general cognitive status may be
      useful for identifying individuals "at risk" for unsafe driving. However,
      measures of selective attention may serve to better differentiate safe versus
      unsafe drivers, especially in the DAT population.

PMID- 9520931
TI  - The relative contribution of ethnicity versus socioeconomic status in explaining
      differences in disability and receipt of informal care.
AB  - Data from a comparative study of 1975 African American, Puerto Rican, and non
      Hispanic White persons age 60 and older in a large Northeastern city were used to
      investigate the relative contribution of ethnicity and socioeconomic status (SES)
      to explaining differences in the need for and receipt of informal care. It was
      hypothesized that differences in disability would be related largely to SES,
      whereas ethnicity would account for most of the differences in the amount of
      informal care. The results of a path analysis argue in favor of a cultural rather
      than a socioeconomic explanation for between-group differences. SES had no direct
      effect on disability when controlling for ethnicity. Ethnicity did explain
      between-group differences in the amount of care. Even when controlling for
      disability, elders in the two minority groups received more informal care than
      did older White persons. The findings illuminate the important role played by
      ethnicity in explaining an older person's need for and receipt of long-term care
      assistance.

PMID- 9520932
TI  - The effect of education on mortality among older Taiwanese and its pathways.
AB  - The present research examines the impact of education on the mortality of older
      Taiwanese during a 4-year interval from April 1989 to April 1993. Data used for
      this study come from the Taiwan Survey of Health & Living Status of the Elderly
      (1989). The research decomposes the effect of education into the direct effect
      and the indirect effects by means of health status, health behaviors, and social
      relationships. We have shown that, of the total effect of educational attainment
      on the mortality of older Taiwanese, about 83% represents indirect influences by
      means of the 3 mediating factors, particularly health status. On the other hand,
      the magnitude of the direct effect, which might reflect influences of additional
      intervening variables on old-age mortality, is low and not statistically
      significant. The results demonstrate that the apparent strong effect of education
      on mortality among older Taiwanese can be accounted for parsimoniously through 3
      major pathways.

PMID- 9520933
TI  - Sociodemographic mortality differences among the oldest old in Finland.
AB  - This study examined mortality differences and trends by several sociodemographic
      characteristics among the Finnish elderly aged 80 years or over during the period
      of 1971-90. The analyses were based on comprehensive data sets compiled by means
      of linking individual death records and census records for the entire population
      of Finland. Poisson regression was applied as the main statistical tool. For both
      sexes, life expectancy at age 80 was about 1 year longer among those with a
      higher education than among those with basic education. A similar difference was
      found between former upper nonmanual workers and manual workers. Slightly lower
      than average mortality was observed among the married, among those living in
      Western Finland, and among the Swedish-speaking population. Mortality declined
      during the study period in all subgroups, with no consistent signs of either
      convergence or divergence of mortality levels. The results suggest that at least
      some further decline of mortality even among the oldest old is possible.

PMID- 9520934
TI  - Career trajectories and older men's retirement.
AB  - The idea of a long and stable career rewarded by retirement is a fixture of the
      American social ethos and political economy. The paradox is that many Americans'
      careers do not fit this image. Here, we examined how the structure of the career,
      as compared to only those circumstances proximate to retirement, is important for
      understanding career endings. Based on labor force histories drawn from the
      National Longitudinal Survey of Older Men, we observed that the occupational
      roles held through the mid and late career combine additively to influence
      retirement and disability experiences, with different conditions of work coming
      into play depending on the career stage. Occupational roles in the mid career
      also have long-term, indirect effects, operating through the onset of health
      problems and the adequacy of pension benefits. Although retirement and disability
      are not hinged to occupational mobility per se, these career endings are
      sensitive to major discontinuities in the career and work role in terms of
      unemployment and labor force mobility.

PMID- 9520935
TI  - The persistence of race and ethnicity in the use of long-term care.
AB  - We examine the use of nursing homes, formal personal care, informal Activities of
      Daily Living (ADL) assistance, and no care to identify racial differences in
      their use. Using the 1987 National Medical Expenditure Survey of both nursing
      homes and the community, multinominal logistic regressions controlled for
      predisposing, enabling, and need variables as well as other types of service use.
      Additional state-level variables make few changes in race/ethnicity parameters,
      indicating that race/ethnicity are not simply proxies for state-level variables.
      Older African Americans are less likely to use nursing homes than similar whites,
      with the lower institutionalization replaced by a higher use of paid home care,
      informal-only care, and no care. This suggests that formal in-home community care
      is not fully compensating for the racial differences in nursing home use.
      Persistent effects of race/ethnicity could be the result of culture, class,
      and/or discrimination that may impair equitable access to services.

PMID- 9520936
TI  - Reed-Sternberg cell: survival in a hostile sea.
AB  - In contrast to the non-Hodgkin's lymphomas, little is known regarding the origin,
      genetics, and function of the Reed-Sternberg cell of Hodgkin's disease. Unlike
      other cancers, the neoplastic cell of Hodgkin's disease, the Reed-Sternberg cell,
      is vastly outnumbered by a surrounding intense inflammatory infiltrate. How this
      rare neoplastic cell originates, persists, and disseminates in a presumably
      hostile cellular environment has remained a mystery. Understanding the biology of
      the Reed-Sternberg cell has been impeded by the rarity of the cell in tumor
      tissue. Herein, we describe how the application of single-cell genetic analysis
      has revealed a clonal and, possibly, germinal center B-cell origin of the Reed
      Sternberg cell. By phenotype and function, Reed-Sternberg cells are highly
      interactive with their cellular microenvironment through cell-cell adhesion,
      expression of members of the tumor necrosis factor receptor superfamily, and
      elaboration of cytokines. Perhaps by their mimicry of immune system cells with
      antigen-presenting function, Reed-Sternberg cells mediate the unusual clinical
      and pathologic features of Hodgkin's disease: intense tissue inflammatory
      infiltrate, fibrosis, and constitutional symptoms.

PMID- 9520937
TI  - Modulation of the plasminogen activator/plasmin system in rat liver regenerating
      by recruitment of oval cells.
AB  - The proteolytic cascade involving plasminogen activators and plasmin appears to
      have an important function in tissue regeneration. We have investigated the
      expression and cellular localization of urokinase-type plasminogen activator
      (uPA), tissue-type plasminogen activator (tPA), urokinase-type plasminogen
      activator receptor (uPAR), and plasminogen activator inhibitor-1 (PAI-1) as well
      as plasminogen activation in rat liver regeneration by recruitment of progenitor
      (oval) cells. Using a model in which surgical partial hepatectomy is combined
      with feeding of 2-acetylaminofluorene (2-AAF) to induce liver regeneration by
      proliferation and differentiation of oval cells, expression of uPA, uPAR, and PAI
      1 was detected by immunohistochemistry mainly in the duct-like formations of
      expanding oval cells. Plasminogen activation, as assessed by direct zymography on
      frozen liver sections, was located over the expanding oval cell populations but
      not over mature hepatocytes. Plasminogen activation was not detected in control
      liver. Expression of uPA, uPAR, and PAI-1, as assessed by immunohistochemical and
      Northern blot analyses, was also observed, when cells located in and in close
      proximity to the bile epithelial structures were activated to enter DNA-synthesis
      in response to 2-AAF, and after in vivo infusion of various growth factors. Given
      the physiologic function of plasminogen activation in fibrinolysis, and
      plasminogen activators in activation of latent growth factors, the selective
      expression of the plasminogen activator/plasmin proteolytic cascade in oval cells
      expanding during liver regeneration in response to the combination of 2-AAF and
      partial hepatectomy, may confer a proliferative advantage to these cell
      populations in an extracellular matrix containing both fibrin and latent growth
      factors.

PMID- 9520938
TI  - Objective nuclear grading for node-negative breast cancer patients: comparison of
      quasi-3D and 2D image-analysis based on light microscopic images.
AB  - In a retrospective investigation for a new image-analytical nuclear grading
      method, we used 145 routine hematoxylin and eosin-stained, paraffin-embedded
      tissue sections from node-negative breast carcinomas. Cell fields of primary
      tumors were scanned in a light microscope in successive focus levels in 1-micron
      steps for thick sections (> or = 5 microns: quasi-3D analysis) and in one focus
      position for thin sections (< 5 microns: 2D analysis). After image-segmentation,
      nuclear features for texture and chromatin distribution were calculated. A binary
      classification tree was constructed for determination of two mathematically
      defined classes of high- and low-risk tumor cell nuclei. After fixing a cut-point
      for the portion of high-risk tumor cell nuclei per patient, it was possible to
      distinguish two different groups with significantly different relapse rates of
      4.2% and 74.5% in quasi-3D analysis and 0.0% and 52.0% in 2D analysis,
      respectively. Large differences between quasi-3D and 2D analysis were only
      present in the classification of nonrelapse patients, whereas nearly all patients
      with relapse had more than 50% high-risk tumor cell nuclei. The results show that
      the information in thicker tissue sections contains important additive components
      in the third dimension, with respect to the detection of chromatin structure and
      distribution. This advantage should be exploited for the development of an
      objective image-analytical nuclear grading system as a highly significant
      prognostic marker.

PMID- 9520939
TI  - A particular characteristic of IgH complementarity-determining region 3 suggests
      autoreactive B-cell origin of primary gastric B-cell lymphomas.
AB  - To clarify the origin of tumor cells and the possible role of antigen in the
      pathogenesis of mucosa-associated lymphoid tissue (MALT) lymphoma, we analyzed
      the third complementarity determining region of IgH gene in nine primary gastric
      B-cell lymphomas by PCR. The presence of vacA gene of Helicobacter pylori was
      also determined. These cases were diagnosed histopathologically as three low
      (extranodal marginal zone B-cell lymphoma)- and three high-grade MALT lymphomas
      and three diffuse large-cell lymphomas without evidence of MALT lymphoma. All
      cases showed a monoclonally rearranged JH band. A single dominant clone was
      detected by sequencing the IgH CDR3 regions in eight cases. In the remaining
      cases. In the remaining case, two major sequences were identified.
      Complementarity-determining region 3 (CDR3) sequences in lymphoma cell clones of
      seven cases showed 61% to 81% homology with autoantibody-associated lymphocyte
      clones including rheumatoid factor. The N-D-N region in the low-grade MALT
      lymphoma group was significantly longer than in the high-grade lymphoma groups.
      Although vacA gene of H. pylori was detected in five of nine cases, all lymphoma
      cell clones showed no association with foreign antigen. These results indicate
      that autoantigen may be responsible for the clonal selection of lymphoma cells,
      and thus autoimmunity may play a role in the pathogenesis of primary gastric B
      cell lymphomas.

PMID- 9520940
TI  - Differential expression of p57kip2, a maternally imprinted cdk inhibitor, in
      normal human placenta and gestational trophoblastic disease.
AB  - Evidence has recently been provided to support a role for genomic imprinting in
      the regulation of embryonic implantation and development and placental growth, as
      well as in the pathogenesis of proliferative trophoblastic diseases. The cyclin
      dependent kinase inhibitor p57KIP2 has recently been recognized as a maternally
      imprinted gene. We investigated p57KIP2 expression in first-trimester normal
      placentas from interrupted pregnancy, spontaneous abortions, and different types
      of proliferative trophoblastic diseases using single- and double-marker
      immunohistochemical techniques. In normal placenta, nuclear p57KIP2 expression
      was observed at high frequency (up to 100%) in extravillous trophoblast,
      cytotrophoblast, and implantation-site interstitial trophoblast, but was absent
      in syncytiotrophoblast. p57KIP2 was also expressed in the stromal cells of
      maternal decidua, which was one of the few adult tissues retaining p57KIP2
      expression (most other adult tissues investigated were negative). p57KIP2
      expression was either absent or low in all cases of diploid/tetraploid complete
      moles (20 cases) and in three cases of gestational choriocarcinoma. On the other
      hand, all spontaneous abortions (12 cases) and triploid partial moles (19 cases)
      showed p57KIP2 levels comparable to those observed in normal placenta. These
      findings are in line with the hypothesis that deregulation of genomic imprinting,
      particularly the loss of cell-cycle inhibitors such as p57KIP2, is involved in
      the abnormal development of androgenetic trophoblastic proliferations. In
      addition, this simple immunohistochemical analysis could provide a useful
      diagnostic marker in difficult cases.

PMID- 9520941
TI  - Immunoglobulin VH genes of high-grade mucosa-associated lymphoid tissue lymphomas
      show a high load of somatic mutations and evidence of antigen-dependent affinity
      maturation.
AB  - High-grade mucosa-associated lymphoid tissue (MALT) B-cell lymphoma of the
      stomach shares several features with its low-grade counterpart. The latter is
      nearly invariably associated with Helicobacter pylori, and the tumor cells of all
      MALT lymphomas normally express surface antigen receptors; thus, it is possible
      that the high-grade type, like the low-grade type, is still influenced by
      interaction with antigen. In the present study, we analyzed the immunoglobulin
      heavy chain variable (V)-region genes from eight cases of high-grade MALT
      lymphoma and one case of Burkitt's lymphoma of the stomach. The V-region genes
      revealed somatic mutations in all cases, leading to the conclusion that high
      grade MALT lymphomas derive from antigen-experienced (post-) germinal center B
      cells. Nonrandom distribution of replacement and silent mutations within the gene
      segments in seven of the eight MALT lymphomas indicated that these V-region genes
      were selected by antigen, at least for some period of time. Five of the cases
      showed an unusual mutation pattern that was suggestive of selection by
      autoantigen or superantigen rather than heterogeneous antigen. Analysis for
      intraclonal variations revealed evidence of ongoing mutations in two cases. In
      these cases, the tumor clones probably derived from cells affected by a germinal
      center B-cell reaction, as the microenvironment of the germinal center is
      required for maintenance of an active hypermutation mechanism. On the other hand,
      in another two cases, no evidence of intraclonal variations was found. Thus,
      either these tumor clones were derived from postgerminal center B-cells, or the
      hypermutation mechanism in the germinal center ceased after some period of time.
      Given the mutation pattern, it is possible that high-grade MALT lymphomas emerge
      from further transformation of low-grade MALT lymphomas with accumulation of
      additional mutations in the complementarity-determining regions.

PMID- 9520942
TI  - Interphase cytogenetic evidence for distinct genetic pathways in the development
      of squamous neoplasia of the uterine cervix.
AB  - Human papillomavirus (HPV) infection has been implicated as an etiologic factor
      in most cervical cancers. However, additional genetic alterations are thought to
      be required for the development of a carcinogenic genotype. In the present study,
      interphase cytogenetics utilizing pericentromeric probes specific for chromosomes
      1, 3, 11, 17, 18, and X was performed on paraffin-embedded tissue sections from
      25 high-grade squamous intraepithelial lesions (SILs) and 25 invasive squamous
      cell carcinomas (ISCCs) of the cervix. HPV infection was determined by both in
      situ hybridization and broad-spectrum GP5+/GP6+ PCR. HPV was identified in all
      high-grade SILs (HPV 16, n = 16; 18, n = 2; 26, n = 1; 31, n = 4; 45, n = 1; 66,
      n = 1) and 23 (92%) ISCCs (HPV 16, n = 19; 18, n = 2; 31, n = 1; 39, n = 1).
      Aneusomy was identified in 11 (44%) high-grade SILs and 18 (72%) ISCCs. In 18
      (62%) of these, relative under-representation of chromosomes 3, 11, 17, and/or 18
      was identified (8 high-grade SILs and 10 ISCCs). Tetrasomy of all six chromosomes
      was present in two high-grade SILs but no ISCCs. Twelve (48%) high-grade SILs and
      seven (28%) ISCCs were disomic with all six chromosome probes, and there was no
      relationship between HPV presence or type and chromosome pattern. The presence of
      distinct patterns of numerical chromosome abnormality in these lesions suggests
      that progression to high-grade SIL or invasive carcinoma can occur by more than
      one genetic pathway. The lack of correlation between chromosome pattern and HPV
      type indicates that these pathways are not HPV type-specific. Whether these
      patterns reflect differences in early gene expression, possibly related to viral
      integration, or differences in the biologic properties of HPV type variants
      remains to be established.

PMID- 9520943
TI  - In vitro procollagen synthesis and proliferative phenotype of bronchial
      fibroblasts from normal and asthmatic subjects.
AB  - Asthma is characterized histologically by a bronchial subepithelial fibrosis.
      Cytokines and other mediators released in the asthmatic chronic inflammatory
      microenvironment can activate the repair process that leads to fibroblast
      proliferation and collagen synthesis. To our knowledge, there are no data
      regarding the effect of a chronic inflammatory microenvironment on the phenotype
      of human bronchial fibroblasts. In the present study, we address this issue by
      comparing bronchial fibroblasts isolated from normal and asthmatic subjects in
      terms of: (a) proliferation over cell passage; (b) in vitro lifespan; (c)
      proliferative response to transforming growth factor-beta 1, platelet-derived
      growth factor-BB, dexamethasone, and retinoic acid; and (d) base-line synthesis
      of procollagens I and III. Bronchial fibroblasts from asthmatic subjects
      demonstrated lower DNA synthesis with cell passage than bronchial fibroblasts
      from normals. The in vitro lifespan of asthmatic bronchial fibroblasts was lower
      than in those from normal subjects and was significantly correlated with airway
      responsiveness. Platelet-derived growth factor-BB and dexamethasone increased 3H
      thymidine incorporation in asthmatic bronchial fibroblasts without having any
      significant effect on normal fibroblast proliferation. Transforming growth factor
      beta 1 and retinoic acid had no significant effect on bronchial fibroblast
      proliferation. Base-line procollagens I and III synthesis measurements showed no
      differences between normal and asthmatic fibroblasts. Taken together, these
      results indicate that the chronic inflammatory microenvironment found in asthma
      can modulate some aspects of bronchial fibroblast phenotype.

PMID- 9520944
TI  - Analysis of differential gene expression in human colorectal tumor tissues by RNA
      arbitrarily primed-PCR: a technical assessment.
AB  - RNA arbitrarily primed (RAP)-PCR is a powerful tool for studying differential
      gene expression in cancer cells. Systematic analysis of human tumor samples may
      provide a list of markers with potential application to the diagnosis, prognostic
      assessment, and treatment of the disease. Nevertheless, because of
      characteristics inherent to the samples and technique, artifactual results are
      likely. We have assessed the effects of several factors on RAP-PCR performance to
      determine the sensitivity and reproducibility of the technique, as well as the
      accuracy of its results, under different conditions in human cell lines and in a
      series of 129 paired human normal colonic mucosa-colorectal carcinoma samples.
      Our results show that RAP-PCR provides reliable fingerprints in a relatively wide
      spectrum of circumstances, including variations in RNA concentration and
      contamination by DNA. Densitometric analysis indicated that relative band
      intensity variations more than 20% were reproducible in 95% of the cases. Serial
      analysis of paired normal-tumor cases yielded a number of bands that were
      recurrently either underexpressed or overexpressed in tumor relative to normal
      mucosa. These differentially expressed bands are prime targets of research
      because they represent candidate tumor-specific up- or down-regulated genes with
      a relevant role in carcinogenesis.

PMID- 9520945
TI  - Development, progression, and androgen-dependence of prostate tumors in probasin
      large T antigen transgenic mice: a model for prostate cancer.
AB  - Probasin (PB) gene product is prostate-specific, epithelial cell in origin, and
      androgen-regulated. A large 12-kb promoter fragment of the PB gene (LPB) was
      linked to the simian virus 40 (SV40) large T antigen (Tag) deletion mutant (that
      removes the expression of the small t antigen) to deliver consistently high
      levels of transgene expression to the transgenic mouse prostate. Seven male
      founders, their male offspring, and all the male offspring from two female
      founders developed at least prostatic epithelial cell hyperplasia by 10 weeks of
      age, indicating that the incidence of transformation was 100%. Tumorigenesis in
      the LPB-Tag animals progressed in a manner similar to that observed in the human
      prostate. Initially, multifocal proliferating lesions were detected in the
      prostatic epithelium, which continued to progress into hyperplasia involving the
      entire epithelium and then low-grade dysplasia. Reactive stromal proliferation
      was induced and continued to develop throughout the progression to high-grade
      dysplasia, carcinoma in situ, and adenocarcinoma. Immunohistochemical studies
      indicated that most stromal cells stained positively for both androgen receptor
      and smooth muscle alpha-actin, suggesting that stromal overgrowth largely
      represented mesenchymal cells that had differentiated into smooth muscle cells.
      Epithelial cell transformation was accompanied by the down-regulation of
      differentiated function, as suggested by the loss of dorsolateral prostate
      specific secretory proteins. Tumor growth was regarded as androgen-dependent
      because tumors regressed in animals castrated at 11 weeks of age, and androgen
      treatment restored both epithelial/stromal cell ratio and tumor growth.
      Furthermore, small populations of prostatic epithelial cells in castrated animals
      continued to proliferate, suggesting the potential for androgen-independent
      growth. Although prostatic metastasis to other organs was not observed, local
      invasion was detected. In summary, the LPB-Tag animal model is unique in that it
      is the only model generated with the Tag alone, thereby eliminating any
      influences of the small t antigen on prostate tumor formation. Moreover, this
      model undergoes molecular changes similar to those found in human prostate
      including: (a) the multi-focal nature of tumorigenesis, (b) the progressive
      histopathologic changes from low- to high-grade dysplasia similar to human
      prostatic intraepithelial neoplasia, (c) stimulation of reactive stromal
      proliferation, and (d) the androgen-dependent growth of the primary tumor. Thus,
      the LPB-Tag prostate tumor model will be useful for studying the sequential
      mechanisms underlying the development of multistep tumorigenesis.

PMID- 9520946
TI  - Synergy between glycated human serum albumin and tumor necrosis factor-alpha for
      interleukin-8 gene expression and protein secretion in human retinal pigment
      epithelial cells.
AB  - Chemokine production by human retinal pigment epithelium (HRPE) cells is believed
      to play an important role in ocular inflammation and immune responses. In our
      previous studies, we demonstrated that glycated human serum albumin (GHSA)
      strongly stimulates HRPE cells and human corneal keratocytes to produce
      chemokines. In the present study, we further examined the effects of GHSA on TNF
      alpha- and IL-1 beta-induced HRPE IL-8 and monocyte chemoattractant protein (MCP)
      1 gene expression and protein secretion in HRPE. At maximally effective
      concentrations, GHSA (2000 micrograms/ml) potentiated TNF-alpha (20 ng/ml)
      stimulated HRPE IL-8 secretion approximately 7-fold. Consistent with the above
      observations were the time- and dose-dependent increases in the steady-state IL-8
      mRNA after coadministration with these two factors, although the half-life of IL
      8 mRNA (30 minutes) was not altered by GHSA. In contrast to IL-8, the TNF-alpha
      induced HRPE MCP-1 gene expression was only slightly enhanced by GHSA. Moreover,
      potentiation of HRPE IL-8 generation by GHSA appeared to be selective for TNF
      alpha because, under similar conditions, GHSA was unable to enhance the IL-1 beta
      stimulated IL-8 gene expression and protein secretion. The IL-1 beta-stimulated
      HRPE MCP-1 production was also unchanged by GHSA. Collectively, these results
      suggest specific potentiation of TNF-alpha-induced HRPE IL-8 by human serum
      albumin that has been glycated either during circulation or locally within
      tissue. This interaction may be relevant to a variety of ocular diseases
      involving breakdown of the blood-retinal barrier.

PMID- 9520947
TI  - Amplification of c-erbB-2 in gastric cancer: detection in formalin-fixed,
      paraffin-embedded tissue by fluorescence in situ hybridization.
AB  - A total of 396 adenocarcinomas of the stomach were examined immunohistochemically
      using antibodies specific for the internal domain of human c-erbB-2 protein.
      Forty of these (consisting of 35 well-differentiated and 5 undifferentiated
      types) overexpressed c-erbB-2, as evidenced by cytoplasmic membrane staining;
      these tumors were further examined by fluorescence in situ hybridization using a
      cosmid probe for 17q11.2-12 (c-erbB-2 locus) on formalin-fixed, paraffin-embedded
      tissues. This technique enabled us not only to detect c-erbB-2 amplification on a
      cell-by-cell basis, but also to compare the gene amplification with the protein
      expression, observe topographical distribution, and establish quantitative
      pictures of the amplification in vivo condition. In all 40 tumors, we observed
      gene amplification and found that the cancer cell with the amplification
      corresponded to the cells overexpressing c-erbB-2. In eight mucosal carcinomas,
      signals were coalesced to one or two clusters, indicating that the amplified gene
      resided in a homogeneous staining region (HSR). Among 32 carcinomas invading
      beyond muscularis mucosae, approximately half were mostly composed of cells with
      the amplification; the others had populations of tumor cells with and without
      amplification, which were sometimes in separate zones or areas and sometimes
      mixed together. In 22 cancers, the amplified genes were exclusively in HSR;
      however, cancer cells with multiple scattered signals-suggesting that the
      amplified genes were translocated to other chromosomes-were found exclusively in
      6 tumors and concurrently with HSR in 4 tumors. These findings suggest that: (a)
      the amplification produces c-erbB-2 in the HSR form generally early in the
      carcinogenesis of gastric adenocarcinomas; and (b) in the process of cancer
      development, the amplified gene is lost in some cancer cells by uneven
      segregation of HSR in mitosis, whereas in others, it is kept in HSR or
      translocated to other chromosomal positions, thereby preserving overexpression of
      c-erbB-2 protein.

PMID- 9520948
TI  - Brain capillary endothelial cells express MBEC1, a protein that is related to the
      Clostridium perfringens enterotoxin receptors.
AB  - Brain capillary endothelial cells compose the blood-brain barrier, which has a
      crucial role in maintaining the normal extracellular environment of the central
      nervous system. We have developed a method to isolate endothelial cells from
      mouse brain and maintain them in a relatively pure primary culture. Using a
      subtractive hybridization technique, a novel cDNA, termed MBEC1 (mouse brain
      endothelial cell 1), has been isolated from the cultured mouse brain capillary
      endothelial cells. MBEC1 is a 1435-bp cDNA predicted to encode a protein of 218
      amino acids. The predicted protein is similar to those of the newly characterized
      Clostridium perfringens enterotoxin receptors and is the mouse homolog of a
      recently described human cDNA clone, which is hemizygously deleted in individuals
      with velo-cardio-facial syndrome and DiGeorge syndrome. MBEC1 was expressed in
      our cultured MBEC, in freshly isolated MBEC, in a variety of mouse organs, and in
      mouse embryos as early as embryonic Day 7. In situ hybridization and
      immunocytochemical analyses revealed the presence of the MBEC1 mRNA and its
      protein product in brain capillary endothelial cells, as well as in a subset of
      other endothelial and epithelial cells. Moreover, developmental regulation of
      expression of MBEC1 was present in respiratory epithelium. Our research thus
      provides a new molecule for further study of the function of normal and abnormal
      blood-brain barrier as well as of other specialized endothelia and epithelia.

PMID- 9520949
TI  - Elevated c-Src protein expression is an early event in colonic neoplasia.
AB  - The molecular events regulating the development and progression of colonic
      neoplasia are currently being delineated. Recent studies have implicated c-Src
      protein kinase activation as an early event in the malignant transformation of
      colonic epithelial cells. However, increased c-Src activity has also been
      reported in colon carcinomas as well as in metastatic hepatic and extrahepatic
      colon carcinomas. To further investigate the potential role of c-Src in the
      progression of colonic neoplasia, we analyzed c-Src levels by
      immunohistochemistry in 27 colorectal resection specimens. Mouse monoclonal
      antibody to c-Src protein was applied to 3-micron sections from formalin-fixed,
      paraffin-embedded tissues using the avidin-biotin-peroxidase method. The
      combination of adenomatous (AD) and adjacent carcinomatous mucosa (CA) specimens
      were present in 20 of 27 patients. In 15 cases, synchronous metastatic (MT)
      lesions were available for evaluation. Strong c-Src expression was evident in 95%
      of AD (n = 20), in contradistinction to 32% of MT (n = 19) and 14% of CA (n =
      22). Weak-to-moderate c-Src expression was seen in adjacent normal colonic mucosa
      (NM) in 96% of cases. Signed rank test univariate analysis revealed a
      statistically significant difference in c-Src expression between NM/AD (p =
      0.0001), NM/CA (p = 0.0001), NM/MT (p = 0.0006), AD/CA (p = 0.0001), and AD/MT (p
      = 0.0002). No significant correlation between levels of c-Src expression and
      patient survival, tumor size, histologic grade, or tumor configuration was
      observed using the Cox's Regression Model. Similar results were obtained by
      analysis of c-Src protein levels and c-Src kinase activity as measured by Western
      blot and in vitro kinase assays of representative cases. Our results indicate
      that: (a) elevated c-Src expression is an important early event during colorectal
      carcinogenesis; (b) its activation may be involved in tumor progression in a
      subset of colonic carcinomas; and (c) additional molecular events are necessary
      for invasion to occur.

PMID- 9520950
TI  - The multiple and changing faces of access.

PMID- 9520951
TI  - Department of Veterans Affairs.

PMID- 9520952
TI  - The association between health care coverage and the use of cancer screening
      tests. Results from the 1992 National Health Interview Survey.
AB  - OBJECTIVES: The authors investigated whether utilization of six different cancer
      screening tests (mammography, clinical breast exam, Pap smear, Fecal Occult Blood
      Test, and Digital rectal exam) varied according to type of health care coverage.
      METHODS: Data on the use of cancer screening tests and coverage in two age groups
      from a 1992 nationally representative cross-sectional survey of approximately
      9,400 adults were analyzed. Multiple logistic regression analysis was used to
      estimate proportions of persons screened according to type and extent of
      coverage, adjusted for socioeconomic, demographic, and health status
      characteristics. RESULTS: Persons aged 40 to 64 years with Medicaid coverage were
      equally as likely to receive five of six cancer screening tests as those with
      private fee-for-service coverage, and both groups were much more likely to be
      screened (70% higher for all six tests) than those who had no coverage. In
      contrast, persons aged 65 years and older who had supplemental private fee-for
      service insurance in addition to Medicare were more likely to receive five of six
      tests than those with Medicare and Medicaid or those with Medicare only. For all
      six screening tests, managed care enrollees at all ages were approximately 10%
      more likely to be screened than persons enrolled in private fee-for-service
      plans. Fecal Occult Blood Test (25% versus 20%) and digital rectal exams (44%
      versus 38%) in persons aged 40 to 64 years and mammography (59% versus 48%) and
      Fecal Occult Blood Test screening (38% versus 30%) in the elderly were
      significantly more frequent for persons in managed care plans. CONCLUSIONS: The
      extent of fee-for-service insurance coverage in the traditional indemnity US
      health care system was positively associated with the use of cancer screening
      tests. The authors found less difference in use of cancer screening between
      managed care and fee-for-service care in 1992 than we expected based on earlier
      research comparing use of preventive services in health maintenance organizations
      with fee-for-service care.

PMID- 9520953
TI  - The costs and outcomes of restricting public access to poison control centers.
      Results from a natural experiment.
AB  - OBJECTIVES: The authors examined the costs and outcomes resulting from a natural
      experiment during which direct public access to poison control centers was
      restricted and then restored. METHODS: Both societal and health care purchaser
      perspectives were used. Probability data were obtained from a natural experiment
      during which public callers from a large county in California were electronically
      blocked from directly accessing the poison control center. Callers were referred
      to 911, which had direct access to the poison control center, if they thought
      they had a poisoning emergency. We conducted telephone interviews of: (a) persons
      who attempted to call the poison control center for a child's poisoning exposure
      but who did not have direct access (n = 270) and (b) persons who called the
      poison control center after direct access was restored (n = 279). Cost data were
      obtained from primary data collection and from other sources. The outcome measure
      was the appropriateness of the treatment location (at home or at a health care
      facility). Caller-reported outcomes were also examined. RESULTS: The average
      additional cost per blocked call was $10.89 from a societal perspective, or
      $33.14 from a health care purchaser perspective. Fourteen percent of callers with
      restricted access were treated at an inappropriate location, compared with only
      2% of callers with direct poison control center access. Also, 14% did not obtain
      any professional advice after they attempted to call the poison control center,
      although 66% of these cases involved potentially toxic substances. Results were
      robust across a range of sensitivity analyses. CONCLUSION: Restricting direct
      public access to poison control centers created additional costs to society, the
      health care sector, and callers.

PMID- 9520954
TI  - Factors influencing waiting time and successful receipt of cadaveric liver
      transplant in the United States. 1990 to 1992.
AB  - OBJECTIVES: Despite concern about access to liver transplantation, there has been
      no nationally based analysis of patients waiting for cadaveric liver transplant.
      Using data from the United Network for Organ Sharing Organ Procurement and
      Transplantation Network database waiting and recipient lists, we examined the
      influence of medical and non-medical factors on the length of time patients
      waited before transplant and whether they survived the wait. METHODS: The authors
      analyzed 7,422 entries to the waiting list from October 1, 1990 to December 31,
      1992. Using Cox Proportional Hazard models, time to transplant was modelled by
      gender, nationality and ethnicity, age, blood type, medical status (critically
      ill versus non-critical), transplant number (first versus retransplant), United
      Network for Organ Sharing region of the country, and three measures of local
      demand and supply of organs. The risk of dying before being allocated an organ
      was compared with receiving an organ using multiple logistic regression models.
      RESULTS: In addition to differences by medical status, blood type, geographic
      region, and organ supply and demand, it was found that women, Hispanic-Americans,
      Asian-Americans, and children waited longer for transplant, whereas foreign
      nationals and repeat transplant patients waited fewer days. The risk of dying
      before transplant was greater for critically ill and repeat transplant patients,
      as well as for women, older patients, Asian-Americans, and African-Americans.
      Children were less likely to die, as were patients from certain blood groups and
      geographic regions. CONCLUSIONS: Results confirm known patterns of waiting list
      experience for liver transplant patients, but also identify factors previously
      unrecognized as influencing waiting time and outcome. Potential explanatory
      factors and areas for further inquiry are discussed.

PMID- 9520955
TI  - The prospective effect of access to medical care on health-related quality-of
      life outcomes in patients with symptomatic HIV disease.
AB  - OBJECTIVES: This study examined the prospective effect of reported access to
      medical care on health-related quality-of-life outcomes in patients with
      symptomatic human immunodeficiency virus (HIV) disease. METHODS: A cohort study
      was designed with interviews at baseline, follow-up interviews at 3 months after
      baseline, mortality follow-up through 6 months after baseline, and medical record
      reviews for selected baseline clinical data. Participants were HIV-infected
      patients who were receiving ambulatory and/or hospital care at one county-run
      municipal and one Veterans Administration hospital in metropolitan Los Angeles
      and were interviewed about access to medical care (using a reliable 9-item scale
      assessing affordability, availability, and convenience of medical care). Access
      to care reported by this sample was compared with that of 2,471 patients with
      other chronic diseases from the Medical Outcomes Study. The main outcome measures
      were composite scores for physical and mental health-related quality of life 3
      months after baseline, derived from a validated 56-item instrument, scored from 0
      to 100, and controlling for baseline health-related quality of life. RESULTS:
      Overall reported access to medical care in this sample was significantly poorer
      than that for patients with other chronic diseases (means scores were 63 and 73,
      respectively). The sample was categorized into tertiles of initial physical and
      mental health-related quality of life and into groups with initial high versus
      low access to care. Among those in the middle tertile of physical health-related
      quality of life at baseline, those with high access improved in physical health
      scores by 10.2 points relative to those with low access. Those in the low and
      middle tertiles of initial mental health improved in mental health to a
      significantly greater extent for those with high versus low access. There were
      nonsignificant trends toward similar effects for most other subgroups. The
      effects of access on health-related quality-of-life outcomes were generally
      robust in multivariate regression analyses that included CD4, hemoglobin,
      albumin, insurance status, and sociodemographic characteristics. CONCLUSIONS:
      Access to care at baseline predicted better physical and mental health outcomes
      at 3 months for those in the middle tertile of physical health and for those in
      the bottom and middle tertiles of mental health at baseline. Increasing access to
      care for poor public hospital patients with HIV infection may help to improve
      health-related quality-of-life outcomes among selected persons with advanced
      disease.

PMID- 9520956
TI  - A joint choice model of the decision to seek depression treatment and choice of
      provider sector.
AB  - OBJECTIVES: Using a community-based sample of currently depressed subjects, this
      research modeled the joint decision to seek depression treatment and choice of
      provider sector (primary care or specialty mental health). The objective was to
      identify those subject-specific case-mix factors and those provider sector
      specific access measures that significantly impacted this joint decision.
      METHODS: A community-based sample of 435 Arkansans with current depression
      symptoms was compiled using random digit dialing and the Burnam depression
      screener. Study subjects were administered baseline and 6-month follow-up
      surveys. All medical, pharmaceutical, and insurance records were collected and
      abstracted to verify service use and depression treatment. Three discrete choice
      model specifications were tested: sequential binary logit models, a multinomial
      logit model, and a nested logit model. The nested logit model makes less
      restrictive assumptions about the patterns of substitution across treatment
      alternatives than the other model specifications. RESULTS: In the 6 months after
      baseline, 73.3% of the sample did not seek depression treatment, 18.9% sought
      care from a primary care provider, and 7.8% sought care from a mental health
      specialist. A likelihood ratio test identified the nested logit model as the
      preferred model specification (chi 2 < or = 0.05), indicating that the expected
      maximum utility of sector choice significantly affects the decision to seek
      treatment. Provider sector-specific access measures (e.g., insurance coverage and
      availability) significantly impacted sector choice and, thus, the decision to
      seek treatment. Subject-specific case-mix factors (e.g., age, gender, employment
      status, depression severity, and psychiatric comorbidity) significantly affected
      the decision to seek treatment. CONCLUSIONS: Sector-specific access measures
      significantly impact both provider sector choice and the decision to seek
      treatment. Because the primary care and specialty care treatment alternatives
      were more substitutable with one another than with the no treatment option,
      changes in access affected sector choice more than the decision to seek
      treatment.

PMID- 9520957
TI  - Shifting physician prescribing to a preferred histamine-2-receptor antagonist.
      Effects of a multifactorial intervention in a mixed-model health maintenance
      organization.
AB  - OBJECTIVES: This study was undertaken to determine whether a program of
      education, therapeutic reevaluation of eligible patients, and performance
      feedback could shift prescribing to cimetidine from other histamine-2 receptor
      antagonists, which commonly are used in the management of ulcers and reflux, and
      reduce costs without increasing rates of ulcer-related hospital admissions.
      METHODS: This study used an interrupted monthly time series with comparison
      series in a large mixed-model health maintenance organization. Physicians
      employed in health centers (staff model) and physicians in independent medical
      groups contracting to provide health maintenance organization services (group
      model) participated. The comparative percentage prescribed of specific histamine
      2 receptor antagonists (market share), total histamine-2 receptor antagonist
      prescribing, cost per histamine-2 receptor antagonist prescription, and the rate
      of hospitalization for gastrointestinal illness were assessed. RESULTS: In the
      staff model, therapeutic reevaluation resulted in a sudden increase in market
      share of the preferred histamine-2 receptor antagonist cimetidine (+53.8%) and a
      sudden decrease in ranitidine (-44.7%) and famotidine (-4.8%); subsequently,
      cimetidine market share grew by 1.1% per month. In the group model, therapeutic
      reevaluation resulted in increased cimetidine market share (+9.7%) and decreased
      prescribing of other histamine-2 receptor antagonists (ranitidine -11.6%;
      famotidine -1.2%). Performance feedback did not result in further changes in
      prescribing in either setting. Use of omeprazole, an expensive alternative,
      essentially was unchanged by the interventions, as were overall histamine-2
      receptor antagonist prescribing and hospital admissions for gastrointestinal
      illnesses. This intervention, which cost approximately $60,000 to implement,
      resulted in estimated annual savings in histamine-2 receptor antagonist
      expenditures of $1.06 million. CONCLUSIONS: Annual savings in histamine-2
      receptor antagonist expenditures after this multifaceted intervention were more
      than implementation costs, with no discernible effects on numbers of
      hospitalizations. The magnitude of effect and cost savings were much greater in
      the staff model; organizational factors and economic incentives may have
      contributed to these differences. More research is needed to determine the
      generalizability of this approach to other technologies and managed care
      settings.

PMID- 9520958
TI  - Improvement scaling (rehabilitation version). A new approach to measuring
      progress of patients in achieving their individual rehabilitation goals.
AB  - OBJECTIVES: Accurate measurement of clinically relevant change in individual
      patients undergoing rehabilitation has been an elusive goal. Simple, clinically
      meaningful, patient-centered measures of individual patient change are urgently
      needed. The purpose of this research was the development and testing of
      Improvement Scaling (Rehabilitation Version)(IMS), a new approach to measuring
      the progress that rehabilitation patients make during treatment. METHODS:
      Research and clinical staff developed the 65 IMS scales and applied them to all
      admissions to an an inpatient rehabilitation unit. Date were collected on 292
      consecutively admitted rehabilitation patients who were aged 50 or older. An
      Improvement Score indicates the degree to which each patient achieves the
      expected level of outcome on his or her unique set of IMS goals. Improvement
      scores were compared to Goal Attainment Scores and to scores from more
      traditional measures. Interrater reliability was assessed. RESULTS: IMS scores
      correlated r = .78 with comparable Goal Attainment Scores. IMS and Goal
      Attainment Scores had the same pattern of correlations with other measures.
      Interrater reliability of IMS scores was r = .91. CONCLUSIONS: IMS appears to be
      a practical, reliable, valid, and clinically useful technique for measuring
      individual patient change. What is needed now is replication and more information
      on factors which may influence IMS scores. Versions of IMS are being developed
      for home health care and mental health. Applications of IMS for quality
      assurance, quality improvement, and documentation of patient change for third
      parties is discussed.

PMID- 9520959
TI  - Time series monitors of outcomes. A new dimension for measuring quality of care.
AB  - OBJECTIVES: Despite the popularity of risk-adjusted outcomes as quality of health
      care indicators, their instability with time and their inability to provide
      reliable comparisons of small volume providers have raised questions about the
      feasibility and credibility of using these measures. In this article the authors
      describe a new analytic strategy to address these problems by examining risk
      adjusted mortality with time, "Time Series Monitors of Outcome" (TSMO), and its
      application to cardiac surgery performed throughout the Department of Veterans
      Affairs between April 1987 and September 1992. METHODS: Expected operative
      mortality for 24,029 patients undergoing coronary artery bypass surgery at all 43
      centers performing this procedure was estimated using a logistic regression model
      to adjust for patient-specific risk factors. The ratio of observed-to-expected
      operative mortality was calculated for each hospital for each of the 11 6-month
      periods. Poisson regression models were used to identify high and low outlier
      hospitals based on significant deviation from the 5.5 year overall mean and/or
      the individual hospital's trend of observed-to-expected ratios with time.
      RESULTS: This method identified four high and one low outlier hospitals based on
      significant deviations from the overall mean and three upward and seven downward
      trending outlier hospitals based on significant deviations in trend with time. A
      significant downward trend in observed-to-expected ratios of 4% per year also was
      observed for all coronary artery bypass graft procedures performed throughout the
      Department of Veterans Affairs during the last 5.5 year period. CONCLUSIONS: Time
      Series Monitors of Outcome should help reduce misclassification of outliers due
      to random variation in outcomes as well as provide more reliable comparative
      information from which to evaluate provider performance.

PMID- 9520960
TI  - Patient noncompliance in the managed care setting. The case of medical therapy
      for glaucoma.
AB  - OBJECTIVES: The authors identify demographic and clinical characteristics
      associated with noncompliance in patients beginning medical therapy for the
      treatment of glaucoma in a managed care setting. METHODS: The authors describe a
      retrospective cohort study in a group-model health maintenance organization in
      Massachusetts. Patients were members of the health maintenance organization who
      were newly initiated on topical drug therapy to treat open-angle glaucoma during
      the period January 1, 1987 through December 31, 1990, who met eligibility
      requirements, and who had evidence of health services utilization for a 12-month
      follow-up period. For all study subjects, we determined the number of days
      without available therapy for glaucoma during the 12-month period. Study subjects
      who did not fill prescriptions adequate to provide medication to cover at least
      80% of days during the study period were considered noncompliant. Logistic
      regression analysis was used to assess demographic and clinical factors
      independently associated with noncompliance among patients initiated on medical
      therapy for the treatment of glaucoma. RESULTS: Of 616 subjects who met inclusion
      criteria, 152 (24.7%; 95% confidence interval, 21.3%-28.1%) met the study
      definition for noncompliance. These patients had an average number of days
      without therapy during the 12-month study period of 103.9 +/- 70.0 days compared
      with 6.8 +/- 19.5 days for those categorized as compliant. Of a variety of
      selected demographic and clinical characteristics, having fewer visits with an
      ophthalmologist during the study period (< 2) was most strongly related to
      noncompliance (odds ratio 2.99; 95% confidence interval 2.03, 4.40). There were
      no differences in average intraocular pressure between the compliant and
      noncompliant groups during the study period. CONCLUSIONS: Noncompliance with
      prescribed medical therapy for glaucoma was found to be common in a managed care
      setting characterized by essentially unrestricted access to health care and
      medications. It remains difficult to identify noncompliant patients based on
      demographic and clinical characteristics. The use of automated prescription data
      to identify noncompliant patients is feasible in large managed health care
      insurance programs where such data are collected routinely for administrative
      purposes.

PMID- 9520961
TI  - Assessing the value of a new pharmaceutical. A feasibility study of contingent
      valuation in managed care.
AB  - OBJECTIVES: The authors assessed the feasibility and construct validity of the
      contingent valuation method for measuring the monetary value to healthy enrollees
      in a health maintenance organization of a new drug, filgrastim, as prophylaxis
      against febrile neutropenia after chemotherapy treatment for cancer. METHODS: A
      random sample of 220 enrollees from a closed-panel staff-model health maintenance
      organization who did not have cancer were interviewed. Chemotherapy, febrile
      neutropenia and filgrastim were described by video and decision board. Questions
      were asked in two different scenarios: (1) User-based: Assuming they were at the
      point of consumption and about to receive chemotherapy, what is the maximum they
      would be willing to pay to receive filgrastim? and (2) Insurance-based: Given
      they were at risk of cancer in the future, what is the maximum they would be
      willing to pay in additional monthly insurance premiums to add filgrastim to the
      plan? In a second insurance scenario where respondents were told that filgrastim
      was covered, what is the minimum reduction in premium that persons were willing
      to accept to relinquish coverage of the drug? A 2 x 2 factorial design was used
      to contrast two bidding algorithms to test for starting point bias and two 5
      yearly prior risks of cancer, 1/200 versus 1/100. Main effects were tested by
      ANCOVA controlling for age, sex, health, and income. RESULTS: Demographics of
      experimental cells were similar. No evidence was found of significant starting
      point bias. For user-based questions, as expected, willingness-to-pay increases
      with febrile neutropenia risk reduction, but at a declining marginal rate.
      Despite careful presentation of information to respondents, willingness-to-pay
      for insurance was higher in the lower prior risk group. Consistent with previous
      contingent valuation studies, the authors of the present study found evidence
      that willingness-to-accept exceeds willingness-to-pay for coverage of the same
      benefit. CONCLUSIONS: An insurance-based contingent valuation study is feasible
      in a health maintenance organization. Construct validation evidence was
      encouraging, with the exception of the test for prior risk of cancer; however,
      this was a between-person contrast and may have been confounded by other factors.

PMID- 9520962
TI  - Physician variability and uncertainty in the management of breast cancer. Results
      from a factorial experiment.
AB  - OBJECTIVES: The purpose of this research was to determine the influence of
      patient and physician characteristics on physicians' level of variability and
      certainty in breast cancer care. METHODS: One hundred twenty-eight physicians
      viewed a videotape of a simulated physician-patient interaction in which the
      patient has an "atypical" breast lump. Six patient characteristics (age, race,
      socioeconomic status, physical mobility, comorbidity, presentation style) were
      manipulated experimentally, resulting in a balanced set of 32 different
      "patients." Physician subjects were recruited to fill four equal strata defined
      by specialty (surgeons versus nonsurgeons) and experience (< or = 15 or > 15
      years since graduation from medical school). RESULTS: More than half of the
      physicians offered a diagnosis of benign breast disease, a third offered a
      diagnosis of breast cancer, and the rest believed that the patient had a normal
      breast or something "other." Results also indicated that physicians' level of
      certainty and test ordering behavior varied with the diagnosis that was offered.
      Of the six patient characteristics, only socioeconomic status influenced
      physician certainty; physicians were more certain of their diagnosis when the
      patient was of a higher socioeconomic status. Surgeons were found to be more
      certain of their diagnosis compared with nonsurgeons. However, surgeons were less
      likely to order radiologic tests or a tissue sample for metastatic evaluation
      than were nonsurgeons. CONCLUSIONS: Overall, physicians displayed considerable
      variability and uncertainty when diagnosing and managing possible breast cancer.

PMID- 9520964
TI  - Biomedical risk factors for hospital admission in older adults.
AB  - OBJECTIVES: This study examines the influence of risk factors such as cigarette
      smoking, blood pressure, serum cholesterol, or chronic illness on frequency of
      hospital admission in a population-based sample. METHODS: Data from the National
      Health and Nutrition Examination Survey I Epidemiologic Followup Study for 6,461
      adults aged 45 years and older were used to assess the influence of risk factors
      measured by interview, physical examination, and laboratory tests on frequency of
      hospital admission over a 12- to 16-year follow-up period. Cox proportional
      hazard regressions were estimated separately for men and women and for ages 45 to
      64 years and 65 years and older. SUDAAN software was used to correct for
      clustering, stratification, unequal weighting, and multiple observations per
      respondent. RESULTS: Risk of hospitalization was higher for current but not
      former smokers (relative risk [RR] = 1.17-1.34 for different age-sex groups; P <
      0.01), higher blood pressure (RR = 1.25-1.28 for ages 45-64; RR = 1.07-1.15 for
      ages 65 and older; P < 0.01), and lower serum albumin (RR = 1.08-1.14; P < 0.01).
      Diabetes, lung conditions, heart attack, and ulcer each were associated with
      higher risk in at least three of the four age-sex groups, as was arthritis among
      the middle-aged (45-64 years). Serum cholesterol was not associated with
      hospitalization. CONCLUSIONS: Chronic conditions with high morbidity as well as
      many factors associated with mortality are associated with a higher frequency of
      hospitalization.

PMID- 9520963
TI  - Reducing loss-to-follow-up among women with abnormal Pap smears. Results from a
      randomized trial testing an intensive follow-up protocol and economic incentives.
AB  - OBJECTIVES: This study evaluates the efficacy of two interventions designed to
      reduce loss-to-follow-up among women with abnormal Pap smears. METHODS: The two
      interventions were evaluated in two large public hospitals using a randomized 2 x
      2 factorial design. One intervention involved an intensive follow-up protocol
      that relied on multiple attempts (mail and telephone) to contact the patient. The
      second intervention provided patients with economic vouchers to offset out-of
      pocket expenses associated with the follow-up visits. Loss-to-follow-up was
      addressed by medical chart reviews and telephone interviews. RESULTS: The study
      population (n = 1453) was primarily Hispanic, married or otherwise living with a
      significant other, relatively young in age, and with no source of payment for
      health care. Overall, 30% of the total sample was loss-to-follow-up (i.e., no
      return visits). Among patients assigned to the control condition, loss-to-follow
      up was 36.1% compared with 27.8% for the intensive follow-up condition, 28.8% for
      the voucher condition, and 29.0% for the intensive follow-up plus voucher
      condition. Both intervention conditions significantly improved follow-up rates.
      The odds ratio for intensive follow-up was 1.56 compared with 1.50 for the
      voucher intervention. The combined intervention condition (intensive follow-up x
      voucher program) did not have a significant effect after taking into account the
      main effects of the two interventions. Correlates of loss-to-follow-up included
      age (younger women had lower return rates), race/ethnicity (African American
      women had lower return rates), live-in relationship (women who were not married
      or living as married had lower return rates), and severity of the abnormal Pap
      smear (less severe abnormalities were associated with lower return rates).
      CONCLUSIONS: Both interventions were associated with moderate reductions in loss
      to-follow-up in this underserved population. The implications of these findings
      are discussed relative to implementing cervical cancer control programs within
      state and local health departments.

PMID- 9520966
TI  - Reliability of an Arabic version of the RAND-36 Health Survey and its equivalence
      to the US-English version.
AB  - OBJECTIVES: The objectives of this research were to: (1) evaluate the reliability
      and equivalence of the Arabic and English versions of the RAND-36 Health Survey
      (RAND-36) in a sample of Saudi Arabian citizens; and (2) assess the health status
      of a sample of Saudi Arabian citizens using both the Arabic and English versions.
      METHODS: Both the Arabic and English versions of the survey were administered to
      a convenience sample of bilingual (English and Arabic) Saudi citizens (n = 415)
      at Saudi ARAMCO Company, Dhahran, Saudi Arabia. Internal consistency, equivalent
      forms, and test-retest reliability were estimated for the eight multi-item scales
      in the Arabic and English versions. Mean scale scores were calculated for each
      version and compared with the general US populations. RESULTS: The median
      Cronbach's alphas for the Arabic RAND-36 in multiple subgroups exceeded 0.70 for
      every scale except one. Two of the English RAND-36 scales had median Cronbach's
      alphas that exceeded 0.70; the remainder exceeded 0.50. Two-week test-retest
      correlations were all statistically significant for both versions. Product-moment
      correlations to test the equivalence of the corresponding Arabic and English
      versions of the RAND-36 ranged from 0.73 to 0.92. Saudi citizens reported
      significantly higher vitality scores, but significantly lower physical
      functioning, social functioning, and general health perception scores than the
      general US population. CONCLUSIONS: The results provide support for the
      reliability and equivalence of the Arabic and English versions of the RAND-36.
      Additional studies need to be conducted in a representative sample of the general
      Saudi population to further assess the psychometric properties of the Arabic
      version.

PMID- 9520965
TI  - The "questions to ask about your medicines" campaign. An evaluation of
      pharmacists' and the public's response.
AB  - OBJECTIVES: The purpose of this study was to assess the impact of the
      WHO/EuroPharm Forum "Questions to Ask About Your Medicines" campaign on patient
      counseling in Finnish community pharmacies. METHODS: The impact of the campaign
      was assessed by comparing the baseline findings with those at 3 months and 12
      months after the implementation. The research methods involved observation of
      pharmacist-customer interactions, followed by personal interview of the customer.
      RESULTS: The main positive outcome was the manner in which information was
      provided, as the counseling became more customized, more empathy was shown toward
      the customer, and haste was less obvious. The campaign did not increase the
      number of customers asking questions, with 6% asking at least one
      pharmacotherapeutic question throughout the campaign. Information was given
      mostly on the pharmacists' initiative, with approximately 40% receiving at least
      some oral counseling, mostly regarding how to use the medicine. Approximately 10%
      of the customers were provided with written information. No change was observed
      in the pharmacists' spontaneous provision of oral or written information.
      CONCLUSIONS: The campaign was an attempt to set national and local standards for
      patient counseling in Finnish pharmacies. Further efforts are needed to change
      the content and availability of counseling.

PMID- 9520967
TI  - On estimating costs for economic evaluation in failure time studies.
AB  - Only recently have attempts been made to adjust for the bias censoring can impart
      on economic estimates based on data obtained during a clinical trial. This
      article reviews a suggested approach that adopts techniques developed for
      adjusting for the effect of censoring on estimation of failure time. The authors
      show that this approach does not provide unbiased estimation and explain the
      reason why this is the case.

PMID- 9520968
TI  - The demand for health insurance by employees in a voluntary small group insurance
      program.
AB  - OBJECTIVES: This study examined the decisions of small group employees to enroll
      in prepaid plans offered through Healthcare Group of Arizona (HCGA), a state
      sponsored and state-administered voluntary insurance program. METHODS: The study
      population included 653 potential employee enrollees who were offered the option
      of two health plans between January 1993 and June 1993, with 447 enrolling in one
      of the two plans. Data sources included two telephone surveys, HCGA
      administrative files, and enrollment application forms. RESULTS: The estimates of
      adjusted price elasticity were in the range of -0.12 to -0.24 for employees with
      prior insurance and were in the range of -0.42 to -0.51 for employees without
      prior insurance. The likelihood of enrolling in HCGA increased with log(income)
      and decreased with log(income) squared. The average income elasticity across
      income groups was 0.12. CONCLUSIONS: The results indicate that small group
      employees without prior insurance were more sensitive to the price of health
      insurance than those with prior insurance. Healthcare Group of Arizona health
      plans may have been viewed as inferior goods by high income employees possible
      because of their association with the Medicaid program.

PMID- 9520970
TI  - Physical impairments and functional limitations: a comparison of individuals 1
      year after total knee arthroplasty with control subjects.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to examine the physical
      impairments and functional limitations of individuals with total knee
      arthroplasty (TKA), as compared with individuals with no diagnosed knee disease
      (control subjects). SUBJECTS: Twenty-nine individuals 1 year following TKA (13
      women, 16 men) and 40 age- and gender-matched control subjects (18 women, 22 men)
      were assessed. METHODS: Walking speed, stair-climbing ability, knee torque (in
      newton-meters), and total work performed during 15 repeated contractions were
      evaluated. RESULTS: Walking speeds for men with TKA were 13% and 17% slower at
      normal and fast speeds, respectively. Their stair-climbing ability was even more
      compromised (51% slower). Walking speeds for women with TKA were 17% and 18%
      slower at normal and fast speeds, respectively. Similarly, their stair-climbing
      time was more compromised (43% slower). Men with TKA were 37% to 39% weaker and
      performed 36% to 37% less total work of their knee extensors compared with the
      control subjects. Similarly, women with TKA had knee extensor strength deficits
      of 28% to 29% and performed 24% less total work. CONCLUSION AND DISCUSSION: One
      year after TKA, marked physical impairments and functional limitations persisted.
      [Walsh M, Woodhouse LJ, Thomas SG, Finch E. Physical impairments and functional
      limitations: a comparison of individuals 1 year after total knee arthroplasty
      with control subjects.

PMID- 9520971
TI  - Accuracy of observational kinematic assessment of upper-limb movements.
AB  - BACKGROUND AND PURPOSE: This study investigated the accuracy of physical
      therapists' visual judgments about kinematic features of the upper-limb movements
      of people without neurological impairments and people with neurological
      impairments following a cerebrovascular accident (CVA). SUBJECTS: Ten experienced
      physical therapists served as observers. Eleven people with a primary diagnosis
      of cortical or subcortical CVA and 4 older individuals without neurological
      impairments participated as "performers." METHODS: The performers were videotaped
      as they completed a transport task. Three videotapes were edited to form three
      physical scales of peak movement speed, jerkiness, and hand path indirectness. On
      two occasions, therapists viewed these videotapes and made judgements about each
      performance on visual analog scales. Therapists' visual judgments were then
      compared with criterion measures determined by three-dimensional instrumented
      analysis. RESULTS: The accuracy of the therapists' judgments was investigated
      using regression methods. Therapists were able to make moderately to highly
      accurate judgments of movement speed (r > or = .87), jerkiness (r > or = .78),
      and hand path indirectness (r > or = .68). These judgements remained highly
      stable over time (r > or = .82). Differences in therapists' judgement models,
      evident from slope and intercept variability in the regression models, were
      reflected in lower intertherapist agreement (intraclass correlation coefficients
      = .65-.85). CONCLUSION AND DISCUSSION: Experienced physical therapists accurately
      and reliably judged kinematic aspects of performance using observational
      assessment. Observational kinematic assessment warrants further systematic
      investigation.

PMID- 9520972
TI  - Effects of energy-matched pulsed and continuous ultrasound on tumor growth in
      mice.
AB  - BACKGROUND AND PURPOSE: A diagnosis of cancer is a contraindication for the use
      of therapeutic ultrasound (US). Continuous US applied to murine tumors has
      resulted in larger and heavier tumors compared with controls. We compared tumor
      growth using low-power continuous US and energy-matched pulsed US. SUBJECTS:
      Female C57BL/6 mice (N = 174) were used. METHODS: Animals received subcutaneous
      injections of methylcholanthrene tumor cells. The mice were randomly divided into
      three groups: 60 mice that received low-power continuous US for 5 minutes at 0.75
      W/cm2 (LC US group), 63 mice that received pulsed US for 12.5 minutes at 1.5
      W/cm2 (pulsed US group), and 51 mice that served as a control group. The LC and
      pulsed US groups received equal US energy. Both experimental groups received 10
      treatments of 3-MHz US, which was applied directly over the tumor. The control
      group received identical handling but no US. After treatment, the tumors were
      excised, weighed, and measured. A one-way analysis of variance, followed by
      Newman-Keuls post hoc testing, was used to analyze the data. RESULTS: Mean tumor
      weights (in grams) and volumes (in cubic millimeters) were 0.563 g and 564 mm3
      for the LC US group, 0.560 g and 525 mm3 for the pulsed US group, and 0.516 g and
      406 mm3 for the control group. CONCLUSION AND DISCUSSION: Reducing total US
      energy will result in less growth of murine tumors. When infusing equal energy,
      continuous and pulsed US will produce similar effects on tumor growth.

PMID- 9520974
TI  - Therapists' conceptualization and characterization of the clinical concept of
      spinal stiffness.
AB  - BACKGROUND AND PURPOSE: The clinical concept of spinal stiffness provides one
      basis for applying spinal manipulation. Because the terms used to describe the
      perceptual results of manual spinal stiffness testing are poorly defined, the
      nature and number of attributes contained in the concept remain unclear. This
      study attempted to clarify the concept of spinal stiffness by examining the
      relationships among 31 published spinal stiffness descriptors using cluster
      analysis. SUBJECTS AND METHODS: Each stiffness descriptor was printed on a
      magnetized rubber strip. Physical therapists in Houston (Tex) and Sydney (New
      South Wales, Australia) judged the similarity of the stiffness descriptors by
      arranging them on a board. The squared Euclidean distance between words was
      calculated, and cluster analysis was performed using Ward's method. RESULTS:
      Cluster analysis reduced the 31 stiffness descriptors to three superclusters
      (limited mobility, increased mobility, and viscoelasticity) in both the Houston
      and Sydney data. CONCLUSION AND DISCUSSION: In a step toward improving the
      reliability of spinal stiffness judgments, this study has identified the
      fundamental characteristics of the clinical concept of spinal stiffness. Research
      is now needed to clearly define these characteristics and then develop protocols
      that will allow physical therapists to reliably rate these attributes.

PMID- 9520973
TI  - The effect of exercises on walking distance of patients with intermittent
      claudication: a study of randomized clinical trials.
AB  - BACKGROUND AND PURPOSE: There is no consensus about the indication for exercises
      for patients with intermittent claudication of the lower extremity and the
      characteristics of an exercise program to improve walking distance. The effect of
      walking is assessed by a systematic review of randomized clinical trials.
      METHODS: Literature databases were accessed using the relevant key words. The
      references of identified articles were screened for additional studies. A
      checklist was developed to screen the studies with respect to the variables of
      interest. A methodological assessment form was developed to assess the
      methodological quality of the studies (maximum possible score: 100). RESULTS:
      Eighty-two articles were identified, of which 21 studies were considered relevant
      for inclusion in the review. Following the analysis of the articles, 11 studies
      were for various reasons eliminated, leaving 10 studies for the systematic
      review. The score for methodological quality of the studies ranged from 47 to 75
      (mean = 62.5, SD = 8.5). Percentage of improvement in walking distance or time
      ranged from 28% to 210% (mean = 105%, SD = 55.8%). CONCLUSION AND DISCUSSION: All
      studies showed that walking exercises improved walking distance in patients with
      intermittent claudication. Further research is needed to determine the optimal
      exercise program, the effect of adherence to the treatment protocol, and the
      duration of the effects following a formal exercise program.

PMID- 9520975
TI  - A statistical profile of physical therapists, 1980 and 1990.
AB  - BACKGROUND AND PURPOSE: To plan for future needs, human resource analysts require
      demographic data. In this research, US census data were used to develop a profile
      of physical therapists. SUBJECTS: Data were extracted from the Public Use
      Microdata Samples of the US censuses of population from 1980 and 1990. Samples of
      3,112 physical therapists from 1990 and 1,530 therapists from 1980 were obtained.
      METHODS: A profile was generated by use of descriptive statistics to examine
      geographic distribution, social characteristics, employment characteristics, and
      income. Linear regression was used to determine factors that influence income.
      RESULTS: During the 1980s, physical therapy demonstrated remarkable growth, with
      trends in physical therapist location, gender, age, and place of employment. Even
      as the profession aged, it stayed an occupation composed predominantly of women,
      but one less concentrated in hospitals. Geographically, physical therapists
      remained clustered in the Northeast and along the Pacific Coast. Income generated
      by physical therapists was predicted by social and geographic characteristics.
      CONCLUSION AND DISCUSSION: This study presents a new data source to examine
      physical therapist characteristics. It provides information necessary for health
      care planners and analysts to better understand the nature of the profession and
      those who practice.

PMID- 9520976
TI  - Free-radical toxicity and antioxidant medications in Parkinson's disease.

PMID- 9520978
TI  - Correction for ties.

PMID- 9520977
TI  - Hamstring muscle stretching.

PMID- 9520979
TI  - Hepatic imaging. An overview.
AB  - Recent advances in ultrasound, CT scan, MR imaging, and scintigraphy permit
      characterization of a variety of focal and diffuse liver diseases. Accurate
      clinical information, however, is of vital importance in selecting the optimal
      imaging modality and interpreting the study accurately. Using a combination of
      radiologic findings and clinical information, a correct diagnosis may be achieved
      noninvasively.

PMID- 9520980
TI  - CT scan of the liver.
AB  - Since its inception, CT scan has had a dominant role in hepatic imaging. Recent
      advances including helical CT scan and bolus-triggered scan initiation software
      packages have had a significant impact. Issues regarding volume, rate of
      administration, and type of intravenous contrast are being distilled.
      Workstations for three-dimensional data reconstructions are producing images that
      compete with conventional angiography in certain areas, while angiographically
      assisted CT scan is being refined in others.

PMID- 9520981
TI  - MR imaging techniques of the liver.
AB  - This article reviews the currently available MR imaging techniques that are
      useful for the detection and characterization of focal and diffuse liver
      pathology. The implementation and clinical utility of various T1-weighted, T2
      weighted, T2*-weighted, and MR angiographic sequences are described.

PMID- 9520982
TI  - Liver-specific MR imaging contrast agents.
AB  - Liver-specific MR imaging contrast agents consist of iron oxide particles or
      specially designed paramagnetic complexes targeting either the reticulo
      endothelial system of the liver or the hepatocytes. These agents enhance the
      relaxation of water molecules in normal liver tissue and are excluded from
      abnormal tissue, such as metastases. Relaxation enhancement provides a map of
      normal liver function, increasing conspicuity of focal abnormalities.
      Understanding the indications and use of these agents is a central challenge for
      radiologists practicing liver MR imaging.

PMID- 9520983
TI  - Ultrasonography. Update on liver technique.
AB  - Sonography is very useful in the evaluation of the patient with severe liver
      disease before and after the placement of a TIPS, and before and after organ
      transplantation. Efforts to use ultrasound to evaluate for primary and metastatic
      lesions to the liver have been reviewed. With its Doppler and color flow
      capabilities, ultrasound remains an important modality for hepatic imaging,
      especially in the evaluation of portal vein patency and hepatic artery
      thrombosis.

PMID- 9520984
TI  - Scintigraphic techniques for hepatic imaging. Update for 2000.
AB  - Nuclear medicine continues to evolve from a generic imaging approach to a
      collection of imaging techniques that are disease-specific. In-111 octreotide
      SPECT scan has quickly become the method of choice to image gastrinoma. A number
      of other agents have a role in other tumor models. FDG imaging of the liver is in
      its infancy, but has potential to outperform anatomic methods (CT scan, MR
      imaging), particularly in the detection of colorectal cancer metastases. The
      imaging of FDG in nuclear medicine involves rapidly evolving technology and has
      the potential to diffuse to the community level practice. To further face the
      controversial areas head on, another problem for nuclear medicine's role in
      hepatic imaging remains its somewhat separate existence from radiology.
      Frequently, the abdominal imager or the general radiologist is in the best
      position to recommend a scintigraphic liver study. A broad knowledge of these
      techniques by all radiologists is essential for their ultimate success.

PMID- 9520985
TI  - Benign lesions of the liver.
AB  - Although many hepatic lesions can overlap significantly in their imaging
      appearance, an imaging approach that is based upon identifying the pathologic and
      functional components of a lesion can aid in distinction from other entities. In
      this manner, the diagnostic evaluation can be tailored using the appropriate
      imaging modality for the lesion at hand. An understanding of the benign liver
      lesions based on the cellular line of origin and subsequent functional components
      aids in grasping their expected imaging appearance and may aid in their
      distinction from malignant tumors. Thus, an imaging approach leading to diagnosis
      of these tumors should be based on this underlying knowledge of the functional
      components and cells within the lesion to be studied. For lesions with Kupffer's
      cell activity, such as FNA, Tc-99m sulfur colloid scan or MR imaging with SPIO
      may yield the most diagnostic information. For lesions such as hepatic cysts or
      angiomyolipoma, the diagnosis is usually not a dilemma. For hemangiomas, the most
      commonly encountered benign hepatic lesion, distinction from other entities may
      be readily apparent from the initial CT scan or US examination, or it may require
      additional evaluation with MR imaging. Finally, for other lesions with many
      cellular components, such as HCA, the imaging findings may not be specific enough
      by any modality to preclude tissue diagnosis. In any case, it is important to
      know the diagnostic accuracy and limitations of the imaging modalities available
      for assessment of any given benign hepatic mass.

PMID- 9520986
TI  - Primary hepatic malignant neoplasms.
AB  - Although metastatic disease is by far the most common form of neoplastic
      involvement of the liver, a variety of primary hepatic malignant neoplasms may
      develop from any of the cell types within the liver. Primary hepatic neoplasms
      include hepatocellular carcinoma, intrahepatic cholangiocarcinoma, biliary
      cystadenocarcinoma, and a variety of mesenchymal tumors. This article reviews the
      clinical presentation and pathology of these tumors and discusses their
      sonographic, CT scan, and MR imaging appearance.

PMID- 9520987
TI  - Hepatic metastases.
AB  - Developments in ultrasound, CT scan, and MR imaging have increased our ability to
      detect and characterize focal liver lesions. Advances in the medical and surgical
      treatment of secondary liver tumors have continued to challenge these advances in
      radiology. A successful outcome depends on knowledge of the size and location of
      the tumor burden, and accurate radiologic assessment is crucial to identify those
      subgroups who may benefit from surgery and to prevent unnecessary radical surgery
      in those likely to gain only a short-term benefit.

PMID- 9520988
TI  - Imaging of diffuse liver disease.
AB  - Imaging can play an important role in the diagnosis and planning of treatment for
      patients with diffuse liver disease. In certain entities, such as iron overload
      disorders, fatty change, Budd-Chiari syndrome, and schistosomiasis, the imaging
      findings are characteristic and diagnostic. In others, the findings are less
      specific, but imaging still has utility in assessment for associated changes of
      cirrhosis and portal hypertension. In either case, familiarity with these diffuse
      hepatic diseases and their expected imaging findings enables an organized and
      thoughtful assessment, with careful attention paid to the key diagnostic features
      and the important sequlae, such as portal hypertension and the development of
      HCC.

PMID- 9520989
TI  - Focal inflammatory disease of the liver.
AB  - Imaging and image-guided intervention have revolutionized management of hepatic
      inflammatory diseases. Pyogenic abscess is preferentially treated percutaneously.
      Radiologic techniques are crucial for the diagnosis of amebic liver abscess and
      infectious conditions of the liver in immunocompromised patients.

PMID- 9520990
TI  - Hepatic calcification.
AB  - Although a specific diagnosis of the calcified liver mass may not always be
      possible, there are some morphologic imaging features that help to indicate the
      diagnosis (Table 1). The radiologist needs to be aware of the wide spectrum of
      diseases of the liver that can calcify, and the most common causes. Pathologic
      correlation with axial imaging has greatly enhanced our understanding and
      interpretation of the underlying liver lesion, which may help to differentiate
      benign from malignant etiology.

PMID- 9520991
TI  - CT scan evaluation of blunt hepatic trauma.
AB  - Information provided by CT scan allows for determination of the extent of liver
      injury and identification of other nonhepatic abdominal injuries. This
      information, coupled with clinical assessment, can be used to optimize
      management. Contrast-enhanced CT scan can monitor progression or resolution of
      hepatic injuries, detect complications, and guide percutaneous treatment of some
      complications. This article discusses CT scanning technique; classification,
      sites, and mechanisms of liver injury; CT scan appearance of liver injury; and
      complications of hepatic trauma.

PMID- 9520993
TI  - Imaging of hepatic transplantation.
AB  - This article provides a clinical overview of liver transplantation. Preoperative
      radiologic imaging methods are discussed. Relevant surgical anatomy is
      illustrated, including vascular and biliary anastomoses. The radiologic features
      of vascular complications in liver transplantation are also reviewed.

PMID- 9520992
TI  - Pediatric hepatic imaging.
AB  - Common indications for liver imaging in children include trauma, suspected mass,
      pre-liver transplantation, monitoring after liver transplantation, jaundice, or
      liver dysfunction. This article highlights areas where the pathology or imaging
      approach in children differs from that seen in adults. Topics covered include
      imaging of a suspected hepatic mass, neonatal jaundice, and segmented liver
      transplantation.

PMID- 9520994
TI  - Liver imaging. A surgeon's perspective.
AB  - This article reviews the segmental anatomy of the liver, which is the basis of
      modern hepatic surgery. Liver regeneration and the factors affecting liver
      volumes and the pathophysiology of the atrophy-hypertrophy complex are discussed.
      Benign and malignant focal liver lesions are reviewed from a surgeon's
      perspective. Finally, an imaging strategy is proposed and treatment options
      outlined.

PMID- 9520995
TI  - The effects of human immunodeficiency virus in the central nervous system.
AB  - More than a decade after the first description of HIV DNA in the nervous system
      the pathophysiology of HIVD remains largely enigmatic, with data supporting a
      number of potential mechanisms for the development of neuronal dysfunction.
      Nevertheless, a few key findings have considerable support in the literature
      devoted to this subject: 1. HIV dementia is caused by HIV itself; no other
      pathogen has been consistently found in the brains of patients with HIVD. 2. In
      comparison with other viral encephalopathies, there appears to be a significant
      discordance between the amount of virus being produced in the brains of patients
      with HIVD and the degree of neurological deterioration. 3. The key cell types
      responsible for viral production within the CNS are the resident macrophages or
      microglial cells. 4. Other elements within the CNS, particularly astrocytes, are
      probably infected with HIV as well, but all of these infections are highly
      restricted in terms of production of virus or viral structural proteins. 5. At
      least one component of the pathogenesis of HIVD may be the generation of
      neurotoxins by infected microglia, although the type of neurotoxin, and the
      specific compound most likely to be involved, are quite controversial. Advances
      with combination antiviral therapy have successfully reduced plasma viral load in
      a high proportion of individuals, leading to the speculation (previously almost
      heretical) that it may be possible to eradicate HIV completely from the systemic
      immune system. If that were the case, potential "sanctuary" sites such as the
      immunologically protected CNS might remain as important reservoirs for reseeding
      of lymphoid tissues. Microglia may be particularly suited for this purpose
      because they are long lived, can produce HIV for several weeks (at least in
      culture), and they are apparently relatively immune to virus-induced
      cytopathology such as syncytium formation. One can speculate about several
      scenarios resulting from the continued presence of replication-competent HIV
      within brain. In the worst case, a smoldering infection of the nervous system
      could lead to neurological deterioration without reinfection of systemic immune
      cells. The epidemiological data indicating that HIVD is a disease primarily
      associated with immunodeficiency suggest that the systemic immune system plays a
      role in maintaining virus residing within the CNS under control. Thus it is quite
      possible that this scenario would not occur for many years after the systemic
      infection is controlled. Alternatively, virus could be transported from the CNS
      by circulating lymphocytes and monocytes and reinfect systemic organs. This would
      necessitate restarting therapy for those individuals who were previously thought
      to be cured, but presumably virus within the CNS would not have developed
      resistance to antivirals. In either case, the techniques currently available do
      not permit an accurate assessment of CNS HIV load in living people, and this
      question will remain unanswered until antivirals are discontinued in a few
      individuals with persistently negative tests for systemic virus. In addition to
      this most critical question, the relationship between viral levels and HIVD is
      largely unexplored, as is the possibility that some strains are particularly
      virulent or neuroinvasive. Furthermore, the potential contribution of host
      genotype in the development of dementia is unknown. In view of the strong
      influence of major chemokine receptor (CCR5) truncations on HIV replication, it
      is entirely possible that more discrete genetic polymorphisms have a subtle
      effect on either brain invasion or virulence.

PMID- 9520996
TI  - Viruses in marine brown algae.

PMID- 9520997
TI  - BK and JC human polyomaviruses and simian virus 40: natural history of infection
      in humans, experimental oncogenicity, and association with human tumors.

PMID- 9520998
TI  - The replicative complex of paramyxoviruses: structure and function.

PMID- 9520999
TI  - Core particles of hepatitis B virus as carrier for foreign epitopes.
AB  - To be effective as vaccines, most monomeric proteins and peptides either require
      chemical coupling to high molecular weight carriers or application together with
      adjuvants. More recently, recombinant DNA techniques have been used to insert
      foreign epitopes into proteins with inherent multimerization capacity, such as
      particle-forming viral capsid or envelope proteins. The core protein of hepatitis
      B virus (HBcAg), because of its unique structural and immunological properties,
      has gained widespread interest as a potential antigen carrier. Foreign sequences
      of up to approximately 40 amino acid residues at the N terminus, 50 or 100 amino
      acids in the central immunodominant c/e 1 epitope region of HBcAg, and up to 100
      or even more residues at the C terminus, did not interfere with particle
      formation. The humoral immunogenicity of inserted epitopes is determined by the
      immunogenicity of the peptide itself and its surface exposure, and is influenced
      by the route of application. The probably flexible and surface-exposed c/e1
      region emerged as the most promising insertion site. When applied together with
      adjuvants approved for human and veterinary use, or even without adjuvants, such
      chimeric particles induced B and T cell immune responses against the inserted
      epitopes. In some cases neutralizing antibodies, cytotoxic T cells and protection
      against challenge with the intact pathogen were demonstrated. Major factors for
      the potentiated immune response against the foreign epitopes are the multimeric
      structure of chimeric HBcAg that results in a high epitope density per particle,
      and the provision of T cell help by the carrier moiety. Beyond its use as subunit
      vaccine, chimeric HBcAg produced in attenuated Salmonella strains may be
      applicable as live vaccine.

PMID- 9521000
TI  - The molecular biology of mastreviruses.

PMID- 9521001
TI  - Bacteriophage HK97 head assembly: a protein ballet.

PMID- 9521002
TI  - Mechanisms involved in natural and experimental neuropathogenicity of influenza
      viruses: evidence and speculation.

PMID- 9521003
TI  - The structure and function of nodavirus particles: a paradigm for understanding
      chemical biology.

PMID- 9521004
TI  - Prevalence rates of Borrelia burgdorferi sensu lato in host-seeking Ixodes
      ricinus ticks in Europe.
AB  - Borrelia burgdorferi sensu lato spirochetes have been found in all examined
      Ixodes ricinus (L.) populations in Europe. The overall mean proportions of unfed
      I. ricinus infected with B. burgdorferi s.l. were 1.9% (range 0-11%), 10.8% (2
      43%) and 17.4% (3-58%) for larvae (n = 5699), nymphs (n = 48,804) and adults (n =
      41,666), respectively. However, the results varied according to the method used.
      Cultivation in BSK medium is the least sensitive technique (an average of 11%
      adult ticks found infected), whereas polymerase chain reaction detecting
      spirochetal DNA is probably the most sensitive method (29% adults found
      infected). Microscopic methods (dark field, phase contrast, direct or indirect
      fluorescence) are generally comparable to each other (17-20% adults found
      infected) and should be regarded as standard procedures because they also make
      possible a quantitative estimation of spirochetes in the vector. Some technical
      problems of these methods are discussed.

PMID- 9521005
TI  - Impairment of the inflammatory reaction on implanted Taenia solium metacestodes
      in mice by a T. solium RNA-peptide: a scanning electron microscopy study.
AB  - Inhibition of inflammation by a Taenia solium RNA-peptide (metacestode factor,
      MF) was studied by scanning electron microscopy (SEM). Viable (96%) T. solium
      metacestodes obtained from a naturally infected pig were dissected and implanted
      in treated and control mice, removed at 6 and 12 days postimplantation (p.i.),
      and studied by SEM. At day 6, metacestodes in control mice showed vigorous
      inflammation, whereas in mice treated with MF they were apparently intact with
      exiguous inflammation. Mice immunized with T. solium metacestode antigens showed
      a moderate inflammation; those treated with both MF and T. solium antigens
      presented scanty inflammation. At day 12, metacestodes presented copious
      inflammation and severe damage to the sucker tissues in mice immunized with T.
      solium; in mice treated with either MF or MF and T. solium antigens there was
      only discrete inflammation. These observations illustrate the central role of MF
      in the inhibition of the early events leading to the parasite's destruction by
      means of an inflammatory response.

PMID- 9521006
TI  - Improved disease resistance after Babesia divergens vaccination.
AB  - The efficacy of a new inactivated vaccine against Babesia divergens was evaluated
      by means of inoculation tests. The infection was initiated by i.v. injection of
      blood containing 2 x 10(9) living parasites into splenectomized and non
      splenectomized calves. Clinical status and hematological parameters were
      determined. Serology examinations for antibodies against B. divergens were
      carried out by indirect fluorescent antibody test (IFAT). Non-vaccinated and
      splenectomized animals exhibited experimental infections. In vaccinated and
      splenectomized animals, clinical symptoms and prolonged incubation periods were
      observed.

PMID- 9521007
TI  - Fasciola hepatica development in the experimentally infected black rat Rattus
      rattus.
AB  - The finding of natural infection of Rattus rattus by Fasciola hepatica on Corsica
      has stimulated further research into the role of the black rat in the
      epidemiology of fascioliasis. Corsican black rats were experimentally
      individually infected with 20 metacercariae from cattle and murine isolates
      obtained from naturally infected bovines and black rats. The following results
      were obtained: (a) in R. rattus infected with the cattle isolate, normal adult
      fluke development took place and infection persisted for a long period, with
      emission of eggs showing embryogenic capacity; (b) the development of F. hepatica
      adults paralleled the ontogenetic trajectories observed in other rodent-F.
      hepatica models; and (c) fluke adults obtained in R. rattus infected with the
      murine isolate exhibited a similar pattern. These findings strongly suggest that
      the black rat may be one of the wild reservoirs of F. hepatica and may have
      contributed to the large geographical extent of the disease on Corsica.

PMID- 9521008
TI  - Surface ultrastructure of plerocercoids of Bombycirhynchus sphyraenaicum
      (Pintner, 1930) (Cestoda: Trypanorhyncha).
AB  - Light microscopy studies have previously shown that Bombycirhynchus sphyraenaicum
      is an exceptional trypanorhynch cestode, characterised by a poeciloacanthous
      armature and two enormous bothridia, which overlap parts of the pars bulbosa, a
      character combination unique within the trypanorhynchs. Plerocercoids of B.
      sphyraenaicum from the fish Lates calcarifer (Centropomidae) were investigated by
      scanning and transmission electron microscopy. Results revealed that the tegument
      of the anterior margin of the distal bothridial surface bears three kinds of
      microtriche; palmate microtriches, 8 microns high, with seven to eight digitiform
      processes; equalized filamentous microtriches, 5-6 microns long, with cap and
      base each forming 50% of the length, borne on undulations beneath the palmate
      microtriches, and cap-dominated filamentous microtriches, 5-6 microns long, with
      the cap forming 75% of the length, borne on the apex of putative sensory
      papillae. Integumental connections link the bases of the palmate microtriches,
      forming transverse girdles around the worm, which may serve to coordinate
      traction. At regular intervals between the palmate microtriches are papillae,
      covered with filamentous microtriches extending above the palmate microtriches. A
      cilium emerges from a bulb at the apex of each papilla; other structures in the
      bulb include an electron-dense cuff, and two electron dense collars. The
      posterior part of the bulb tapers and passes into the tegumental cytoplasm. These
      adorned papillae, observed for the first time in trypanorhynch cestodes, are
      identified as putative mechanoreceptors.

PMID- 9521009
TI  - Echinococcus granulosus infection of farm dogs of Iran.
AB  - The prevalence and distribution of Echinococcus granulosus in sheepdogs was
      studied in 13 provinces of Iran, where 90% of the Iranian sheep and goat
      populations and, thus, sheepdogs are found. Worms were found in 27.17% of 390
      dogs successfully purged with 4 mg/kg arecoline hydrobromide. The highest
      prevalence was detected in dogs from the rural areas of Isfahan (central part of
      Iran) and the lowest, in dogs from those of Sistan (Southeast Iran). The
      frequency distribution of E. granulosus was overdispersed, with only a few
      animals harboring heavy infections.

PMID- 9521010
TI  - Tetramicra brevifilum (Matthews & Matthews, 1980) (Microsporida: Tetramicriidae)
      in a new fish host, Lophius budegassa (Spinola, 1807) in Spain.
AB  - Tetramicra brevifilum, a microsporidian parasite of Scophthalmus maximus, was
      found in Lophius budegassa for the first time. This parasite was detected in 5 of
      199 hosts captured in the coastal waters of Barcelona (Northwest Mediterranean),
      which enlarges the geographic distribution of this microsporidian. Affected fish
      did not show any external sign of disease, and cysts of T. brevifilum were found
      associated with the body musculature but were easily differentiated from those of
      Spraguea lophii, another microsporidian present in this host. A case of
      simultaneous infection by both T. brevifilum and S. lophii was found.

PMID- 9521011
TI  - Observation of membrane fusion on the interaction of Trichomonas vaginalis with
      human vaginal epithelial cells.
AB  - The in vitro cytopathic effect of Trichomonas vaginalis on epithelial cells was
      analyzed through the interaction of two parasite strains with freshly collected
      human vaginal epithelial cells (HVECs) from normal women. Videomicroscopy, light
      and electron microscopy (scanning and transmission), freeze-fracture, the tracer
      lanthanum nitrate, and the periodic acid-thio-semicarbazide-silver proteinate
      techniques were used to analyze regions of close contact between the HVECs and T.
      vaginalis. After 2 h of interaction, all HVECs were dead, whereas all the
      trichomonads were alive. Microscopic observations demonstrated that in addition
      to previously described regions of adhesion and interdigitations, areas of
      continuity between the cytoplasm of the two interacting cells were found. They
      were not easy to find since they correspond to focal spots placed in different
      depths of the section. When these regions were depicted, the plasma membranes of
      the T. vaginalis and the vaginal epithelial cells seemed to be fused.

PMID- 9521012
TI  - Development and morphological variability of Echinococcus granulosus.
AB  - Characteristics are presented of Echinococcus granulosus strobila from dogs
      experimentally infected with protoscolices from a single cyst isolated from the
      liver of a domestic pig in a central Slovakian district. Adult cestodes are
      characterized mainly by 28-32 hooks highly variable in shape and size; 26-51
      testes situated mostly throughout the proglottis (1 or 3 rows behind the
      vitelline gland); a lobate ovary; the shape of the uterus, which in 10% of
      proglottides is more or less spherical, in 62% is saccular with lateral
      sacculations of variable size, in 27% is saccular without lateral sacculations
      and in 1% is more or less tubular or strongly ramified; and an intermediately
      rapid rate of development lasting until between 40 and 44 days p.i. The present
      report analyzes the high degree of variability of the clone studied, referring to
      the knowledge on the characteristics of the pig, sheep, and cattle strains of E.
      granulosus and E. multilocularis species, with which some taxonomic characters of
      the clone representatives overlap.

PMID- 9521013
TI  - Effects of free and liposomized praziquantel on the surface morphology and
      motility of Mesocestoides vogae tetrathyridia (syn. M. corti; Cestoda:
      Cyclophyllidea) in vitro.
AB  - The effects of in vitro exposure to praziquantel (PZQ), liposomized PZQ
      (lip.PZQ), and empty liposomes on the surface morphology and motility of
      Mesocestoides vogae tetrathyridia were investigated using scanning electron
      microscopy (SEM) and a motility apparatus. Examination of treated larvae showed
      an effect that was concentration- and time-dependent, involving morphological
      damage that was similar in character for all of the treated groups. The most
      marked effects were a flattening and elongation of the larval body accompanied by
      irregularities in the surface architecture involving the development of
      tegumental protuberances and depressions. Erosion of the surface microvillous
      layer occurred only after overnight incubation, being most pronounced after
      treatment with lip.PZQ. The motility index of treated tetrathyridia corresponded
      well to the SEM observations. The frequency of contractions was maximal in worms
      treated with free PZQ at 25 micrograms/ml in both regimens. However, after
      incubation with lip.PZQ the increase in motility was concentration-dependent and
      of a greater extent. Empty liposomes and lipid mixtures of the same concentration
      and composition resulted in increased motility in treated larvae as compared with
      controls. More extensive tegumental damage and higher motility of larvae occurred
      after lip.PZQ treatment, perhaps resulting from a synergistic action of the drug
      and its associated lipid.

PMID- 9521014
TI  - Ultrastructure of the spermatozoon of the bank vole tapeworm, Paranoplocephala
      omphalodes (Cestoda, Cyclophyllidea, Anoplocephalidae).
AB  - The mature Paranoplocephala omphalodes spermatozoon is filiform, tapered at both
      ends and lacks mitochondria. Its anterior extremity exhibits an apical cone of
      electron-dense material measuring about 900 nm in length and 200 nm in width, and
      two crested-like bodies. The cortical microtubules follow a 25-35 degrees
      helicoidal path along their whole length, except at the posterior extremity where
      they become parallel to the spermatozoon axis. They are arranged in a single or
      two fields which may cover each other partially. The axoneme, of the 9 + "1"
      pattern of the Trepaxonemata, lacks a peri-axonemal sheath and does not reach the
      extremity of the spermatozoon. The nucleus is a compact and irregular cord coiled
      in a spiral around the axoneme. Moreover, we report for the first time a nucleus
      in the spermatozoon of a Cyclophyllidea species which reaches beyond the axonemal
      posterior extremity. The cytoplasm, depending on the level where the section is
      cut, is slightly electron dense or electron lucent and contains numerous small
      electron-dense granules in regions III-V. In the posterior spermatozoon
      extremity, granular material is replaced by a terminal and compact electron-dense
      material.

PMID- 9521015
TI  - Evaluation of quantitative buffy coat analysis in the detection of canine
      Dirofilaria immitis infection: a model to determine its effectiveness in the
      diagnosis of human filariasis.
AB  - Quantitative buffy coat (QBC) analysis has been reported to have a high degree of
      methodical sensitivity in the detection of human filariasis. This study was
      conducted to evaluate its usefulness in the diagnosis of filariasis using a
      Dirofilaria immitis/dog model. By necropsy of 244 stray dogs, 40.6% of the
      animals were found to harbor 1-58 worms of D. immitis (mean 6.5 +/- 8.4
      worms/infected dog). The QBC analysis and thick blood smear (TBS) method detected
      microfilaremia in 31.6% and 21.3% of these dogs, respectively. The results of
      these two methods were highly correlated with the presence of bisexual worms in
      the dogs. The QBC analysis was more sensitive (55% versus 39%) and efficient (79%
      versus 72%) than the conventional TBS method. However, accurate speciation of the
      microfilariae was impossible using the QBC analysis. Although this technique is
      more sensitive, simpler, and less time-consuming and does not require as much
      skill or experience in comparison with the conventional TBS method, the failure
      in speciation of the parasites may limit its usefulness.

PMID- 9521016
TI  - Repeated infections with Haemonchus contortus and Trichostrongylus colubriformis
      in dairy goats: comparison of resistant and susceptible animals.
AB  - A total of 70 strongyle-free French Alpine dairy goats were exposed to a
      combination of sequential and challenge infections with Haemonchus contortus and
      Trichostrongylus colubriformis third-stage larvae. The sequential infection
      consisted of three inoculations at 50-day intervals, each infection being
      abbreviated by anthelmintic treatment at 40 days postinoculation. The challenge
      infection, composed of the same nematode strains, was undertaken 2 months later,
      when goats were at their 1st month of lactation. Fecal egg counts (FECs), packed
      cell volumes (PCVs), pepsinogen concentrations, inorganic phosphate
      concentrations, and peripheral eosinophil numbers were measured at 30-40 days
      after each inoculation. Goats were defined as being resistant or susceptible
      according to their level of nematode egg output following the first inoculation.
      Significant differences in FECs were recorded between the two groups throughout
      the further inoculations and the challenge infection. The reliability of FECs was
      supported by the high repeatability values found within and between infections.
      With regard to blood constituents, only PCVs related to H. contortus infection
      showed values that differed significantly between the two groups, resistant goats
      having higher PCVs after the first and the third inoculations than did
      susceptible animals. However, this difference was not detectable after the
      challenge infection. The milk production yield for the current lactation was
      significantly lower in the resistant goats. Moreover, resistant animals exhibited
      constantly greater body condition scores as compared with susceptible animals.
      These results indicate that the individual responsiveness of dairy goats to
      experimental nematode infection can be estimated on the basis of FECs and PCVs
      (for H. contortus) and is negatively related to the level of milk production of
      the animals.

PMID- 9521017
TI  - Native pulmonary muscular proliferation.
AB  - Four cases with native pulmonary muscular proliferation (NPMP) are reported. The
      etiology of this rare condition is unknown. A hamartomatous process is discussed.
      In spite of its rarity the correct diagnosis of this condition is important. Both
      clinically and histologically in transbronchial biopsies, NPMP may be mistaken
      for pulmonary lymphangioleiomyomatosis (PLAM). Distinction of these 2 conditions
      is adamant, as PLAM has a poor prognosis, and, moreover may be associated with
      general disease, as with tuberous sclerosis. Whereas the typical distribution of
      more mature desmin positive muscle cells in a dense center core and more immature
      desmin negative radiating peripheral muscle cell proliferation with fascicular
      pattern in NPMP may be recognized in open lung biopsy, these differences may not
      become evident in small transbronchial biopsies. Immunohistochemical methods play
      an important role in the differential diagnosis--as with PLAM estrogen and
      progesterone receptors may be expressed and, most importantly, the reaction of
      the HMB45-antibody appears consistently positive in muscle cells of PLAM, while
      negative with NPMP. Thus, recognition of this clinically innocent disease is also
      possible in small tissue particles.

PMID- 9521018
TI  - Inflammatory pseudotumor of the ureter and the urinary bladder.
AB  - Inflammatory pseudotumor (IPS) of the urinary bladder was first described in
      1980. We report four cases of IPS which occurred during the last four years. One
      tumor occurred in the bladder of a 49-year-old woman five months after abdominal
      hysterectomy of uterine leiomyomas, two tumors in a 35- and 39-year-old woman,
      respectively, without antecedental surgical intervention (though one with
      recidive after six months). The fourth occurred in a 64-year-old male in the
      proximal ureter by pyelonephritis. Two cases were initially diagnosed at frozen
      section during operative treatment, the others on paraffine section after
      immunohistochemical examination. Two cases showed an aberrant expression of
      cytokeratines. There is no evidence of recidive tumor within a mean follow up of
      25 months (12-49 months). Features to differentiate benign from malignant spindle
      cell lesions of the lower urinary tract are the absence of atypical mitoses,
      significant cytologic atypia, absence of necroses within the tumor (rather on its
      surface), no destructive growth at the tumor margins and low cellularity.
      Usually, IPS show a submucosal edematous area with a deeper, highly cellular
      component. The clinical history of a recent bladder operation or gynecologic
      surgery is of upmost importance in making the diagnosis of IPS. Complete surgical
      excision, either by transurethral resection or partial cystectomy appears to be
      curative for IPS.

PMID- 9521019
TI  - Expression of VS38 in osteoblasts and stroma cells of bone tumors.
AB  - VS38 is a mouse monoclonal antibody which recognizes an intracytoplasmic antigen
      of 64 kilodaltons present in normal and neoplastic cells. It was reported to be
      of potential value in identifying myeloma or plasmacytoma in bone marrow or other
      tissues. During diagnostic analysis of bone marrow biopsies we noticed a
      consistent staining of osteoblasts with VS38. This led us to investigate the
      immunoreactivity in a range of bone lesions. 58 lesions were examined in the
      current study, including benign and malignant tumors as well as tumor like
      lesions and processes with reactive bone formation. The Streptavidin-peroxidase
      complex technique was applied on paraffin embedded sections, with 3-amino-9
      ethylcarbazole serving as chromogen. All osteoblasts of reactive origin and part
      of the osteoblasts of benign neoplasms showed positive immunostaining. The
      antibody stained stroma cells in 81.25% (13/16) of the cases of benign osteogenic
      tumors and in 82.35% (14/17) of the osteosarcomas. Additionally, VS38 labelling
      was observed in bone tumors of fibrohistiogenic origin such as nonossifying
      fibroma and giant cell tumor, the histogenesis of which is still being debated.
      On the whole, it can be concluded that antibody VS38 lacks specificity as a
      plasma cell marker. It shows, however, a striking affinity to osteoblasts and in
      part also to stroma cells of osteogenic and fibrohistiogenic bone tumors.

PMID- 9521021
TI  - Induced expression of Thy-1 molecules on dermal endothelial cells in skin
      allografts.
AB  - We obtained evidence in a foregoing study that inducible Thy-1 on vascular
      endothelial cells functions as a possible vascular permeability modulator in the
      rat. We now report on the regulation and function of endothelial Thy-1 in skin
      allograft rejection in the rat. While no obvious expression of Thy-1 antigen on
      the vasculature can be seen in normal organs, dermal endothelial cells do express
      Thy-1 during allogeneic skin graft rejection and Freund's complete adjuvant (FCA)
      induced inflammation. The antigen was weakly induced on tubular epithelial, but
      not on endothelial cells during kidney allograft rejection, and not in FCA
      induced inflammation of the kidney. In contrast, Thy-1 antigen was not induced in
      the rejected lung or in FCA-induced inflammation of the lung. This pattern of Thy
      1 regulation was transcriptionally regulated. Administration of anti-Thy-1
      antibodies generated increased vascular permeability in skin allografts, although
      this procedure did not modulate survival of the grafts.

PMID- 9521020
TI  - Pleomorphic xanthoastrocytoma with gangliogliomatous component.
AB  - We describe a composite glio-neuronal tumor comprising pleomorphic
      xanthoastrocytoma (PXA) and ganglioglioma identified in a left temporal biopsy.
      The 32-year-old male patient underwent surgery following a clinical history of
      persistent headaches of 6 years' duration. Immunohistochemical double labeling
      with antibodies to synaptophysin, beta-tubulin isotype III, GFAP and CD44H
      demonstrated neoplastic neurons and astrocytes in the ganglioglioma, while
      coexpression of glial and neuronal markers was found in a subset of PXA tumor
      cells variously showing giant cell or spindle cell morphology. There were gradual
      transitions between the two neoplastic populations. These findings raise the
      possibility of ganglioglioma having evolved by differentiation of bipotential PXA
      tumor cells along astrocytic and neuronal lineages. The PXA may, therefore, be
      closely related to desmoplastic neuroepithelial tumors of infancy, a group of
      neoplasms of presumed embryonal origin.

PMID- 9521022
TI  - Follicular dendritic cell tumor of the mesentery.
AB  - Follicular dendritic cell (FDC) tumor is an exceedingly rare malignant neoplasm
      and occurs mainly in the cervical lymph nodes. We report a mesenteric FDC tumor
      occurring in a 66-year-old female, that manifested with intraabdominal multifocal
      recurrence 7 years after resection of the primary tumor. Histologically, both
      primary and recurrent tumors were composed of oval to spindle cells with paley
      eosinophilic cytoplasms, indistinct cell borders, round to elongated nuclei with
      clear or finely dispersed chromatin, and medium to large nucleoli.
      Characteristically, the tumor cells were growing in sheets, fascicles, and
      sometimes in whorls and a storiform pattern. In addition, focal necrosis, nuclear
      pleomorphism and abnormal mitoses were also observed. The neoplastic cells were
      intimately admixed with small lymphocytes. The diagnosis was confirmed by
      positive immunoreactivity with CD21 and CD35 antibodies and by ultrastructural
      demonstration of convoluted interdigitating cell processes connected by scattered
      desmosome-like junctions. Although our case showed a low proliferative activity
      evaluated by MIB-1, multifocal recurrence has occurred. The clinicopathologic
      features and differential diagnosis of FDC tumors are discussed with the review
      of the literature.

PMID- 9521023
TI  - Inflammatory fibroid polyp in a continent ileo-anal pouch after colectomy for
      ulcerative colitis--case report.
AB  - The most frequent complication occurring in continent ileo-anal pouches after
      colectomy for ulcerative colitis (UC) is pouchitis. Recurrences of adenomas or
      carcinomas in pouches of familial adenomatous polyposis (FAP) patients are
      exceptional, whereas in those with ulcerative colitis dysplasia it is a very rare
      occurrence. We describe the case of a young woman who developed a mass in a J
      pouch three years after its construction following colectomy for ulcerative
      colitis. Histological and immunohistochemical studies showed that this mass had
      the features of an inflammatory fibroid polyp. A review of the literature of
      lesions observed in continent ileo-anal pouches after colectomy for UC would
      suggest that this lesion is an exceedingly rare complication of those devices.

PMID- 9521024
TI  - Recurrent phyllodes tumor in a man.
AB  - The case of a 35-year-old man with a borderline-type cystosarcoma phyllodes is
      presented. Four years after the primary excision of the tumor, wide excision of a
      local recurrence and postoperative radiotherapy were performed. No repeated
      relapse was observed during a 5-year follow-up. Neither significant endocrine
      changes nor genetic alteration could be proven. However, a slightly increased
      SHBG concentration was detected, resulting in a decreased biologically available
      androgen level reduced testosterone/SHBG index. This phenomenon might be a
      consequence of the chronic liver disease of the patient due to his type II
      diabetes mellitus and alcohol abuse. In addition to the conventional
      histopathological examinations, immunohistochemical and electron-microscopic
      investigations were carried out on tissue sections, and the steroid receptors,
      EGF receptors and EGF-like activity of the tumor were also studied.

PMID- 9521025
TI  - Carcinoma in basal cell adenoma of the parotid gland.

PMID- 9521026
TI  - Tumescent infiltration of corticosteroids, lidocaine, and epinephrine into
      dermatomes of acute herpetic pain or postherpetic neuralgia.

PMID- 9521027
TI  - Rapid healing of venous ulcers and lack of clinical rejection with an allogeneic
      cultured human skin equivalent. Human Skin Equivalent Investigators Group.
AB  - OBJECTIVE: To test the safety, efficacy, and immunological impact of a cultured
      allogeneic human skin equivalent (HSE) in the treatment of venous ulcers. DESIGN:
      Prospective, randomized study. SETTING: Multicenter study in the outpatient
      setting. INTERVENTION: Each patient with a venous ulcer received either
      compression therapy alone or compression therapy and treatment with HSE. The
      patients were evaluated for HSE safety, complete (100%) ulcer healing, time to
      wound closure, wound recurrence, and immune response to the HSE. OUTCOME: The
      study was completed as planned in 293 randomized patients. RESULTS: Treatment
      with HSE was more effective than compression therapy in the percentage of
      patients healed by 6 months (63% vs 49%; P=.02, Fisher exact test, 2-tailed) and
      the median time to complete wound closure (61 days vs 181 days; P=.003, log-rank
      test). Treatment with HSE was superior to compression therapy in healing larger
      (> 1000 mm2; P=.02) and deeper ulcers (P=.003) and ulcers of more than 6 months'
      duration (P=.001). Occurrence of adverse events was similar in both groups. No
      symptoms or signs of rejection occurred in response to treatment with HSE, and no
      HSE-specific immune responses were detected in vitro to bovine collagen or to
      alloantigens expressed on keratinocytes or fibroblasts. CONCLUSIONS: Treatment
      with HSE healed venous ulcers more rapidly and in more patients than compression
      therapy alone. There was no clinical or laboratory evidence of rejection or
      sensitization in response to HSE application. These data suggest that HSE
      represents a significant advance in the treatment of venous ulcers, particularly
      those that are difficult to heal.

PMID- 9521028
TI  - Focal hyperhidrosis: effective treatment with intracutaneous botulinum toxin.
AB  - OBJECTIVE: To evaluate the effect of intracutaneous injections of botulinum toxin
      type A on excessive focal hyperhidrosis. DESIGN: Therapeutic before-and-after
      trial over 4 months. SETTING: Neurological and dermatological university
      departments. PATIENTS: Eleven patients with excessive axillary, palmar, or
      plantar hyperhidrosis fulfilling the following criteria: (1) local and systemic
      drug therapy had failed to improve their symptoms; (2) the patients were severely
      disabled with respect to their occupation and social activities; and (3) a
      successful treatment by botulinum toxin would obviate the need for destructive
      surgical procedures. INTERVENTIONS: Three mouse units of botulinum toxin (Botox)
      per 4-cm2 skin area was injected intracutaneously in 16 axillae, 8 palms, and 2
      soles. MAIN OUTCOME MEASURES: Reduction of hyperhidrosis as documented by the
      Minor iodine-starch test and gravimetrical assessment of local spontaneous sweat
      production measured over 1 minute. RESULTS: In all patients, botulinum toxin
      completely abolished sweating in the injected areas (P<.001) within 3 to 7 days.
      No relevant adverse effects occurred and no clinical recurrence of hyperhidrosis
      was observed within the follow-up period of up to 5 months. Occasionally,
      subclinical reactivation of sweat gland function was observed 4 months after
      treatment. CONCLUSIONS: Intracutaneous botulinum toxin seems preferable to any
      hitherto used conservative or surgical procedures and may become the therapy of
      choice in pathological focal hyperhidrosis.

PMID- 9521030
TI  - Acute urticaria in infancy and early childhood: a prospective study.
AB  - OBJECTIVES: To establish the clinical, etiological, and prognostic features of
      acute urticaria in infancy and early childhood and to define its optimal
      management. DESIGN: Prospective study. The inception cohort was collected from
      April 1, 1992, through March 31, 1994. After initial evaluation, the course of
      the disease was assessed at 2 months and after 1 to 2 years. SETTING: Emergency
      department of a regional teaching pediatric hospital (referral center), which is
      also the only pediatric hospital for the general community in the city
      (population, 600,000 inhabitants). PATIENTS: Fifty-seven consecutive infants,
      aged 1 to 36 months, hospitalized with a final diagnosis of acute urticaria.
      Follow-up at 1 to 2 years was available in 40 of 57 patients. INTERVENTION: Oral
      antihistamines (dexchlorpheniramine maleate, terfenadine, or hydroxyzine
      hydrochloride) for 2 weeks. MAIN OUTCOME MEASURES: Recurrence and chronicity.
      RESULTS: Annular or geographic papules and plaques with hemorrhagic lesions were
      seen in 28 patients (49% of cases) and angioedema in 34 patients (60% of cases).
      An underlying cause was suspected or identified in 52 patients (91% of cases).
      Infection, either associated or not with drug intake, was the cause in 46
      patients (81%) and foods were the cause in 6 (11%). Parasitic infestations were
      noncontributory. Hemorrhagic lesions and association with articular symptoms were
      statistically more frequent in urticaria caused by infections. Atopy in the
      patient or family was associated in 33 patients (58% of cases), and particularly
      atopic dermatitis was associated with urticaria caused by food. At 1- to 2-year
      follow-up, 12 (30%) of 40 patients surveyed had chronic or recurrent urticaria.
      CONCLUSIONS: Causative factors in urticaria are dominated by benign viral
      illnesses, often associated with antibiotic drug therapy. In most patients,
      laboratory investigations are not required. Twenty percent to 30% of cases evolve
      into chronic or recurrent disease.

PMID- 9521031
TI  - Scalp dysesthesia.
AB  - BACKGROUND: Cutaneous dysesthesia syndrome is a disorder characterized by chronic
      cutaneous symptoms without objective findings. Patients complain of burning,
      stinging, or itching, which is often triggered or exacerbated by psychological or
      physical stress. These symptoms may be manifestations of an underlying
      psychiatric disorder or may represent a type of chronic pain syndrome.
      OBSERVATIONS: Eleven women presented with chronic severe pain and/or pruritus of
      the scalp only without objective physical findings, a condition we term "scalp
      dysesthesia." Five women described pain, stinging, or burning only; 4 women
      complained of pain and pruritus; and 2 women reported pruritus only. The patients
      ranged in age from 36 to 70 years. The duration of symptoms ranged from 9 months
      to 7 years. Five women had physician-diagnosed psychiatric disorders, including
      dysthymic disorder, generalized anxiety, and somatization. Seven women reported
      that stress triggers or exacerbates their symptoms. Eight women experienced
      improvement or complete resolution of symptoms with treatment with low-dose
      doxepin hydrochloride or amitriptyline hydrochloride. One patient responded
      completely to treatment with sertraline and hydroxyzine hydrochloride but then
      experienced a relapse. CONCLUSIONS: We describe 11 patients with a new syndrome
      that we term scalp dysesthesia. Of 11 patients, 9 benefited from treatment with
      low doses of antidepressants.

PMID- 9521032
TI  - New skin for old: developments in biological skin substitutes.

PMID- 9521029
TI  - Prognostic factors in leukocytoclastic vasculitis: a clinicopathologic study of
      160 patients.
AB  - OBJECTIVE: To analyze risk factors for systemic involvement and long-term course
      in leukocytoclastic vasculitis. DESIGN: A clinicopathological study of 160
      patients with leukocytoclastic vasculitis followed up for at least 3 years.
      Univariate and multivariate analysis were conducted by logistic regression
      methods. SETTING: The Bellvitge Hospital, a referral center in Barcelona, Spain.
      PATIENTS: One hundred sixty patients with cutaneous leukocytoclastic vasculitis.
      Patients in the categories cutaneous/systemic vasculitis and acute/chronic
      cutaneous vasculitis were selected for comparative analysis. MAIN OUTCOME
      MEASURES: Clinical, laboratory, and histopathological findings. RESULTS: Of 89
      females and 71 males, aged 14 to 89 years, systemic involvement was documented in
      20% of cases. Perinuclear-staining antineutrophil cytoplasmic autoantibodies were
      found in 21% of patients and cryoglobulins in 25.4%. Of the patients, 1.9% died
      of systemic vasculitis. The average duration of cutaneous lesions was 27.9
      months. In 67.2%, a cause or associated condition was identified. Of the skin
      specimens, 59.6% showed vasculitis limited to superficial dermal vessels. Direct
      immunofluorescence was positive in 84.3% of cases. In the multivariate analysis,
      paresthesia, fever, and absence of painful lesions were found to be risk factors
      for systemic involvement. Cryoglobulins, arthralgia, and normal temperature were
      risk factors for chronic cutaneous disease. CONCLUSION: Our results identify
      prognostic factors in leukocytoclastic vasculitis and may provide some aid in the
      management of this heterogeneous group of patients.

PMID- 9521033
TI  - Cutaneous vasculitis: what have we learned in the past 20 years?

PMID- 9521034
TI  - The future of medical dermatology.

PMID- 9521035
TI  - Nonhealing neck ulcers.

PMID- 9521037
TI  - Crusted scarring plaques on the upper part of the back.

PMID- 9521038
TI  - Fever and rash complicating a leg ulcer.

PMID- 9521036
TI  - Verrucous nodule of the finger.

PMID- 9521039
TI  - Patients with truncal basal cell carcinoma represent a high-risk group.

PMID- 9521040
TI  - Races, clines, and phototypes.

PMID- 9521041
TI  - Hormone-induced acneiform eruption in human immunodeficiency virus disease.

PMID- 9521042
TI  - Recurrence rates after the first course of isotretinoin.

PMID- 9521043
TI  - Dyshidrotic eczema treated with mycophenolate mofetil.

PMID- 9521044
TI  - Melanocytic nevi in sun-protected Canadian Hutterite children.

PMID- 9521046
TI  - Raindrop seborrheic keratoses: a distinctive pattern on the backs of elderly
      patients.

PMID- 9521045
TI  - Detection and typing of human papillomavirus in skin lesions from renal
      transplant recipients and equivalent lesions from immunocompetent patients.

PMID- 9521047
TI  - Novel mutant mice secreting soluble CD4 without expression of membrane-bound CD4.
AB  - Mutant mice derived from C57BR/cdJ mice were found to have a novel genetic defect
      in CD4 expression. Flow-cytometric analysis demonstrated that there were no CD4+
      cells in either the thymus or the peripheral lymphoid organs of the mutant mice.
      Thymocytes of the mutant mice expressed an amount of CD4 mRNA comparable to
      normal mouse thymocytes, but the mutant CD4 mRNA was slightly smaller in size
      than normal CD4 mRNA. The sequence analysis of the mutant CD4 cDNA obtained from
      thymic RNA revealed that the defect in the CD4 expression was attributable to the
      deletion of the entire exon VIII, encoding a transmembrane domain of the CD4
      molecule. Moreover, soluble CD4 was detected both in the culture supernatant of
      thymocytes and sera from mutant mice. The analysis of the genomic DNA sequence
      elucidated that one thymine was substituted for 14 base pairs at the junction
      between exon VIII and intron VIII in the mutant mice, which could possibly
      account for the alternative splicing of CD4 mRNA. These mutant mice showed
      reduced delayed-type hypersensitivity reactions against sheep red blood cells and
      antibody production against T-dependent antigen but not against T-independent
      antigen. Thus, these mutant mice have a novel defect in CD4 expression where CD4
      mRNA is alternatively spliced to delete a transmembrane domain, giving rise to
      secretion of soluble CD4 instead of expression of membrane-bound CD4.

PMID- 9521048
TI  - Mucosal IL-12 gene delivery inhibits allergic airways disease and restores local
      antiviral immunity.
AB  - Allergic asthma strongly correlates with airways inflammation driven by
      interleukin (IL)-4 and IL-5 secreted by allergen-specific CD4+ T cells. It is
      possible that over-production of these factors in the lungs may render asthmatic
      individuals less able to resolve virus infection of the respiratory tract by down
      regulating type 1 cytokine-driven immune responses. IL-12 is important for the
      establishment of cell-mediated immunity (CMI) and may also inhibit responses
      driven by type 2 cytokine production. Sustained expression of IL-12 in the
      airways may, therefore, represent an effective preventive treatment or therapy
      for allergic asthma and any adverse consequences of excessive production of type
      2 cytokines for the development of local CMI. Here, we show that allergic
      responses in airways profoundly inhibit the development of antiviral CMI in mice
      following local immunization with vaccinia virus (VV) leading to persistent lung
      infection. However, mucosal gene transfer of IL-12 in the lung, via a VV vector,
      inhibited local type 2 cytokine production, both prevented the development of
      allergic disease and airways hyperreactivity in a manner largely dependent on
      endogenous interferon-gamma expression and suppressed established allergic
      disease, and reversed the suppression of local antiviral CMI responses resulting
      in rapid resolution of virus infection. Our study provides the first direct
      demonstration that allergic conditions, particularly in airways, may inhibit
      immune responses to concomitant virus infection and suggests that transient
      mucosal IL-12 gene therapy represents an effective approach to both the
      prevention and treatment of allergic airways disease and associated
      immunosuppression of CMI.

PMID- 9521049
TI  - Selective tolerization of Th1-like cells after nasal administration of a cholera
      toxoid-LACK conjugate.
AB  - Recent reports have suggested that after infection of BALB/c mice with Leishmania
      major, CD4+ T cells responding to a single antigen, LACK (Leishmania homologue of
      receptors for activated C kinase), drive the differentiation of other responding
      T cells to the Th2 phenotype and so allow lesion development to occur. Transgenic
      mice expressing LACK in the thymus are tolerant to LACK and thus resolve
      infection with L. major. The oral administration of soluble protein to mice has
      been shown to result in the peripheral tolerance of antigen-specific CD4+ T
      cells. We therefore sought to tolerize LACK reactive T cells in non-transgenic
      BALB/c mice in order to determine the effectiveness of this tolerization approach
      as an alternative to standard vaccination protocols against L. major infection.
      Surprisingly, oral or nasal administration of up to 8 mg of recombinant LACK did
      not affect the outcome of infection. We therefore conjugated LACK to cholera
      toxin beta subunit (CTB-LACK) which has previously been shown to improve the
      effectiveness of oral tolerance to conjugated antigens. Nasal administration of
      as little as 12 microg of CTB-LACK effectively diminished the capacity of mice to
      mount a subsequent proliferative response to LACK and further delayed the onset
      of lesion development in infected mice. However, pretreatment with CTB-LACK did
      not prevent the eventual onset and progression of disease in these mice. An
      examination of cytokine responsiveness to LACK after tolerization with CTB-LACK
      revealed that while the Th1 response to LACK was suppressed, Th2 cytokine
      production was unaffected. Similar experiments using an ovalbumin-CTB conjugate
      suggested that this selective tolerance of Th1 cells was not specific to the LACK
      protein but may be an effect common to CTB-conjugated proteins.

PMID- 9521050
TI  - Stimulation of P-selectin glycoprotein ligand-1 on mouse neutrophils activates
      beta 2-integrin mediated cell attachment to ICAM-1.
AB  - The entry of neutrophils into inflamed tissues is initiated by cell rolling on
      the blood vessel wall followed by arrest and transendothelial migration. Rolling
      is mediated by the selectins, while the two subsequent steps require activated
      beta 2-integrins. We have investigated whether the binding of P-selectin to mouse
      neutrophils could trigger the activation of beta 2-integrins. We show that cross
      linking of P-selectin glycoprotein ligand-1 (PSGL-1) on mouse neutrophils with an
      antibody-like recombinant form of P-selectin or with monoclonal antibodies
      stimulated the production of reactive oxygen intermediates and enhanced
      neutrophil attachment to intercellular adhesion molecule 1 (ICAM-1)-expressing
      CHO cells. This effect was independent of whether complete antibodies or F(ab')2
      fragments were used. The adhesion-stimulating effect of P-selectin could be
      blocked by monoclonal antibodies against PSGL-1. Increase of cell attachment was
      dependent on lymphocyte function-associated antigen 1 (LFA-1) and on Mac-1, since
      it could be blocked with antibodies against both respective integrin alpha
      chains. Moreover, cell surface expression of Mac-1 increased upon cross-linking
      of PSGL-1. In agreement with published data, treatment of human neutrophils with
      P-selectin-IgG did not enhance attachment to ICAM-1. Our data suggest that
      ligation of PSGL-1 on mouse neutrophils, but not on human neutrophils, activates
      beta 2-integrin mediated cell attachment to ICAM-1.

PMID- 9521051
TI  - Two genes in the rat homologous to human NKG2.
AB  - Two different lectin-like receptors for MHC class I molecules have so far been
      identified on natural killer (NK) cells, the Ly-49 homodimeric receptors in mice
      and the NKG2/CD94 heterodimeric receptors in humans. The recent identification of
      a rat CD94 orthologue implied that NK cell receptors equivalent to NKG2/CD94 also
      exist in rodents. Here we describe the cDNA cloning of two rat genes homologous
      to members of the human NKG2 multigene family. The deduced rat NKG2A protein
      contains a cytoplasmic immunoreceptor tyrosine-based inhibition motif (ITIM),
      whereas the cytoplasmic tail of rat NKG2C lacks ITIM. The genes map to the rat NK
      gene complex and are selectively expressed by NK cells. The expression is strain
      dependent, with high expression in DA and low in PVG NK cells, correlating with
      the expression of rat CD94. Ly-49 genes have previously been identified in the
      rat, and the existence of rat NKG2 genes in addition to a CD94 orthologue
      suggests that NK cell populations utilize different C-type lectin receptors for
      MHC class I molecules in parallel.

PMID- 9521052
TI  - Identification of cytotoxic T cell epitopes within Epstein-Barr virus (EBV)
      oncogene latent membrane protein 1 (LMP1): evidence for HLA A2 supertype
      restricted immune recognition of EBV-infected cells by LMP1-specific cytotoxic T
      lymphocytes.
AB  - Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1) and latent membrane proteins
      (LMP) are the only antigens consistently expressed in malignancies such as
      nasopharyngeal carcinoma (NPC) and Hodgkin's disease (HD). Since EBNA1 is not
      recognized by EBV-specific cytotoxic T lymphocytes (CTL), there is increasing
      interest in the identification of the potential target epitopes within LMP1.
      Although LMP1-specific CTL have been isolated from seropositive individuals,
      earlier attempts to identify the peptide epitopes recognized by these T cells
      have been unsuccessful. In the present report we used a novel protocol to
      identify CTL epitopes within LMP1 which can be recognized by both polyclonal and
      clonal CTL. Firstly, a computer-based program was employed to identify the
      potential HLA-binding peptides within LMP1. Polyclonal CD8+ CTL were then
      isolated from seropositive donors that recognized the peptide epitopes YLLEMLWRL
      and YLQQNWWTL from LMP1 in association with HLA A2. Limiting dilution analysis of
      the memory CTL response revealed that the LMP1-specific CTL response constitutes
      a minor component of the CTL response in healthy virus carriers. Interestingly,
      analysis of YLLEMLWRL-specific CTL revealed that these CTL were able to lyse EBV
      infected B cells expressing different HLA A2 supertype alleles including A*0201,
      A*0202, A*0203, A*0204, A*0206, A*6802 and A*6901. These data strongly support
      the notion that HLA class I supertype-restricted CTL may be of significant use in
      the development of peptide-based immunotherapeutics against EBV-associated
      malignancies in different ethnic populations.

PMID- 9521053
TI  - Genomic analysis of the Tapasin gene, located close to the TAP loci in the MHC.
AB  - The Tapasin molecule is a member of the immunoglobulin (Ig) superfamily required
      for the association of TAP transporters and MHC class I heterodimers in the
      endoplasmic reticulum. In this study, the Tapasin gene was precisely mapped in
      relation to the MHC. The gene was centromeric of the HLA-DP locus between the
      HSET and HKE1.5 genes and within 500 kbp of the TAP1 and TAP2 genes. A homologous
      mouse EST was mapped to a syntenic position on chromosome 17, centromeric of the
      H-2 K locus. Similarly, the rat Tapasin gene was shown to be in an equivalent
      location with respect to the RT1.A locus. The localization of Tapasin, TAP, LMP
      and class I genes within such a short distance of each other on the chromosome
      implies some regulatory or functional significance. We determined the Tapasin
      gene sequence for comparison of its structure to that of other Ig superfamily
      members, such as MHC class I genes. The IgC domain was encoded by a separate
      exon. However, the positions of the other introns were not characteristic of
      other Ig superfamily genes, indicating that Tapasin has a distinct phylogeny.

PMID- 9521054
TI  - Suppression of IL-12 production by phosphodiesterase inhibition in murine
      endotoxemia is IL-10 independent.
AB  - Phosphodiesterase (PDE) inhibitors are potent regulators of various immune
      processes. Immune cells contain type IV and type III PDE. Here we studied in mice
      the effects of rolipram, a selective PDE IV inhibitor, and amrinone, a selective
      PDE III blocker, on plasma levels of IL-12 (p70), IFN-gamma, IL-1, TNF-alpha, and
      nitric oxide (NO) induced by intraperitoneal injection of Escherichia coli
      lipopolysaccharide (LPS) (80 mg/kg). Pretreatment of BALB/c mice with both
      rolipram (1-25 mg/kg) and amrinone (10-100 mg/kg) decreased plasma IL-12 levels
      in a dose-dependent manner. Similarly, LPS-elicited plasma IFN-gamma
      concentrations were suppressed by both rolipram and amrinone. However, LPS
      induced plasma IL-1alpha levels were not affected by either of these compounds.
      In addition, rolipram inhibited IL-12, IFN-gamma, TNF-alpha and nitrite/nitrate
      (breakdown products of NO) production in C57BL/6 IL-10(+/+) mice as well as in
      their IL-10-deficient counterparts (C57BL/6 IL-10(-/-)). Our results suggest that
      rolipram and amrinone decrease the immune activation in endotoxemia through
      inhibition of the production of pro-inflammatory mediators IL-12, IFN-gamma, TNF
      alpha and NO. These effects are not the consequences of the increase in IL-10
      production by PDE inhibition.

PMID- 9521055
TI  - Quantitative control of MHC class II expression by the transactivator CIITA.
AB  - Activation of T lymphocytes is quantitatively controlled by the level of
      expression of MHC class II molecules. Both constitutive and inducible expression
      of MHC class II genes is regulated by the transactivator CIITA, which is itself
      tightly regulated. Since the level of MHC class II molecules expressed is a
      functionally essential parameter, it was of interest to explore whether MHC class
      II expression is quantitatively controlled by the level of the transactivator.
      This report shows that in a variety of experimental conditions one does indeed
      observe, in both mouse and man, a quantitative control of MHC class II expression
      by the level of CIITA. This relationship between the regulator gene, which
      behaves as a rate-limiting factor, and its target genes clarifies our
      understanding of the quantitative modulation of MHC class II expression, and thus
      of T lymphocyte activation.

PMID- 9521056
TI  - The role of macrophages in the induction and regulation of immunity elicited by
      exogenous antigens.
AB  - Different delivery vehicles may target to different antigen presenting cells
      (APC) because of their composition, size and/or physical properties. In this
      study, we examined the priming of cytotoxic T lymphocyte (CTL) responses to a
      soluble exogenous protein in vivo, using various delivery vehicles. In addition,
      we determined the role of macrophages as APC in vivo for each of these delivery
      vehicles by comparing the induction of antigen-specific CTL and serum antibodies
      in normal and macrophage-depleted mice. Influenza A virus-derived virosomes,
      liposomes and monophosphoryl lipid A/squalene (MPLSQ) efficiently induced antigen
      specific CTL as well as antibody responses, of which virosomes proved to be the
      most efficient inducers. In mice that were immunized with cell-associated
      antigen, strong CTL responses but no antigen-specific antibodies were detectable,
      while aluminium hydroxide and aluminium phosphate elicited antigen-specific
      antibodies but no CTL responses. Elimination of macrophages in vivo before
      immunization abrogated CTL responses induced with liposomes and MPL/SQ, but did
      not affect induction of antigen-specific CTL with virosomes or cell-associated
      antigen. Importantly, serum antibody levels were not altered after macrophage
      depletion, regardless of the delivery vehicle used, suggesting that in the
      absence of macrophages, other APC may phagocytose the exogenous antigens for
      major histocompatibility complex (MHC) class II processing and presentation.
      These results suggest that soluble exogenous antigens delivered in different
      carrier systems may be processed differently by different APC in vivo for MHC
      class I- or class II-restricted presentation.

PMID- 9521057
TI  - Administration to mouse of endotoxin from gram-negative bacteria leads to
      activation and apoptosis of T lymphocytes.
AB  - Lipopolysaccharide (LPS) from gramnegative bacteria is a well-known T cell
      independent B lymphocyte mitogen and macrophage/monocyte activator. While the
      conventional view holds that LPS is ignored by T cells, we report here that
      administration of LPS to mice activates all B cells, but also engages most CD4
      and CD8 T cells, as measured by the expression of the activation markers CD69 and
      CD25 and by size increase. T cells recruited in endotoxin-treated mice showed,
      following in vitro stimulation by concanavalin A, altered patterns of cytokine
      production. In vivo, massive T cell apoptosis was evidenced in the days following
      LPS exposure. The present observation may contribute novel insights into the
      mechanisms of endotoxin shock and of the immunological consequences of gram
      negative infections.

PMID- 9521059
TI  - Interferon-gamma maintains the binding and functional capacity of receptors for
      IL-8 on cultured human T cells.
AB  - The neutrophil chemotactic cytokine, IL-8, has been reported to also chemoattract
      T lymphocytes in vitro and in vivo. Previously we showed that freshly isolated T
      cells migrated in response to IL-8, but incubation of T cells at 37 degrees C
      resulted in progressively decreased levels of IL-8 binding sites on T cells in
      association with reduced chemotactic responses. However, this reduced binding and
      migration of cultured T cells in response to IL-8 can be prevented by the
      presence of mononuclear cells in the culture. In order to define the factor(s)
      responsible for the restoration of T cell binding and migration in response to IL
      8, we examined the effects of various cytokines. Addition of IFN-gamma in
      cultured T cells maintained both the CXC chemokine receptor CXCR1 and CXCR2
      binding sites for IL-8 on these cells to the level comparable to that expressed
      on freshly purified T cells accompanied by an almost complete restoration of
      their chemotactic response to IL-8. The results suggest that Th1 cytokine, IFN
      gamma, produced by mononuclear cells stimulated by proinflammatory signals may
      play an important role in regulating IL-8 receptor expression on T cells and in
      sustaining the function of these cells in response to IL-8.

PMID- 9521058
TI  - Interferon-gamma inhibits expression of the long pentraxin PTX3 in human
      monocytes.
AB  - PTX3 is a prototypic long pentraxin expressed by various cell types, most
      prominently monocytes and endothelial cells, in response to interleukin-1 (IL-1),
      tumor necrosis factor (TNF) and bacterial products. In the present report, we
      show that interferon-gamma (IFN-gamma) inhibits the expression of the PTX3 gene
      induced by exposure to IL-1, TNF or lipopolysaccharide in human monocytes. This
      effect is dose dependent and observable when IFN-gamma is added from 24 h before
      up to 3 h after the addition of IL-1. While the time course of the IL-1-induced
      PTX3 mRNA expression is not affected, IFN-gamma reduces the stability of the PTX3
      mRNA as well as its transcription. The inhibition of PTX3 expression is
      restricted to monocytes in that no inhibition occurs in cytokine-stimulated
      fibroblasts and endothelial cells. Under the same conditions, as expected, IFN
      gamma augmented monocyte chemotactic protein-1 expression in the same cell
      preparations. PTX3 protein secretion by activated monocytes is also suppressed by
      exposure to IFN-gamma. Altogether, these data identify a negative pathway of
      regulation mediated by IFN-gamma, which may occur under inflammatory conditions.

PMID- 9521060
TI  - IL-10 interrupts memory B cell expansion in the germinal center by inducing
      differentiation into plasma cells.
AB  - Germinal center (GC) B cells undergo proliferation, somatic hypermutation and
      isotype switching in the course of differentiation into plasma cells to produce
      high-affinity antibodies. To understand the molecular mechanism regulating the
      expansion of memory B cells and the termination of expansion by differentiation
      into plasma cells, we investigated the effect of interleukin-2 (IL-2), IL-4, IL
      10 and CD40 ligand (CD40L) on the differentiation of GC B cells in the defined
      culture system containing a follicular dendritic cell (FDC)-like cell line. IL-2,
      IL-4 and CD40L are required for the optimum proliferation and differentiation of
      GC B cells. When IL-10 was added to this culture condition, CD20+ CD38+ GC B
      cells sequentially differentiated into CD20+ CD38- memory B cells and then CD20-
      CD38+ plasma cells. In the absence of IL-10, the resulting CD20+ CD38- memory B
      cells continued to proliferate and retained its phenotype. The proliferation of
      memory B cells was interrupted by addition of IL-10 which induced the
      differentiation into plasma cells. The expression of CD80 and CD86 was up
      regulated in the memory B cells, compared to naive B cells and plasma cells. The
      identity of memory B cells generated in vitro from GC B cells was further
      substantiated since memory B cells generated in vivo displayed the identical
      pattern of proliferation and differentiation under the same culture condition.
      These results highlight the potent role of GCT helper cells in the expansion and
      differentiation of memory B cells by regulating different cytokine production.

PMID- 9521061
TI  - DNA immunization in relB-deficient mice discloses a role for dendritic cells in
      IgM-->IgG1 switch in vivo.
AB  - A single intraspleen inoculation of plasmid DNA coding for an immunoglobulin
      heavy chain gene initiates immunity and establishes immunologic memory against
      the antigenic determinants of transgenic immunoglobulins, somatic transgene
      immunization. During priming mice produce IgM but not IgG1 antibodies. Since IgM 
      -> IgG1 class switch occurs spontaneously during the primary immune response to
      protein antigens we investigated possible mechanisms for failure of spontaneous
      isotype switch in vivo in this model of immunity. We found that inoculation of
      plasmid DNA in the form of a chimeric gene coding for granulocyte-macrophage
      colony-stimulating factor (GM-CSF) was able to drive IgG1 class switch readily
      after priming. Since GM-CSF activates cells of the dendritic lineage we tested
      the possibility that dendritic cells (DC) may be involved in regulating IgM -->
      IgG1 switch. To this end we used bone marrow chimeras constructed from mice
      carrying the null mutation for the relB member of the NF-kappaB/Rel family as
      these mice lack bone marrow-derived mature DC. RelB (-/-) mice and (-/-) bone
      marrow chimeras inoculated with DNA/GM-CSF did not produce IgG1 antibodies during
      the primary immune response. Since relB (-/-) bone marrow chimeras lack DC of
      donor origin but possess resident follicular dendritic cells we conclude that Ig
      class switch in vivo is regulated by the function of interdigitating dendritic
      cells (IDC). Thus, IDC may contribute to the qualitative aspects of the emerging
      immune response.

PMID- 9521062
TI  - The induction of a protective response in Leishmania major-infected BALB/c mice
      with anti-CD40 mAb.
AB  - A protective immune response to the intracellular parasite Leishmania major
      requires the development of a Th1 CD4+ T cell phenotype. We demonstrate herein
      that BALB/c mice, which normally develop a susceptible Th2 response to L. major
      infection, are protected when co-injected with an agonistic anti-murine CD40 mAb.
      Anti-CD40 mAb-mediated protection in this system was found to be T cell
      dependent, since it was not observed in C57BL/6 x 129 mice that were rendered T
      cell deficient (TCR beta-/- x TCR delta-/-) and L. major susceptible. Anti-CD40
      mAb stimulation of L. major-infected BALB/c mice was accompanied by increased IL
      12 and IFN-gamma production in draining lymph nodes, analyzed either by direct
      expression, or in an antigen-specific in vitro recall assay. The protective role
      of these cytokines was indicated by the finding that anti-CD40 mAb-mediated
      protection of L. major-infected BALB/c mice could be reversed by co-treating the
      animals with neutralizing anti-IL-12 and/or anti-IFN-gamma mAb. Collectively,
      these data suggest that BALB/c mice develop a protective Th1 CD4+ T cell response
      to L. major infection when co-injected with anti-CD40 mAb. While the CD40-CD40L
      interaction has been previously shown to be vital in the control of murine
      Leishmaniasis, the current study establishes in vivo that anti-CD40 mAb treatment
      alone is sufficient to protect BALB/c mice from L. major infection and raises the
      possibility of utilizing this approach for vaccination strategies.

PMID- 9521063
TI  - Stable polarization of peripheral blood T cells towards type 1 or type 2
      phenotype after polyclonal activation.
AB  - Polarization of T lymphocytes towards type 1 (T1) or type 2 (T2) subsets
      producing a distinct array of cytokines plays a role in several diseases and
      could be used for therapeutic intervention. Bearing this purpose in mind, we have
      established suitable in vitro conditions to drive resting polyclonal human T
      cells towards stable T1 or T2 polarization profiles. Unselected peripheral
      lymphocytes from normal donors were primed with soluble anti-CD3 monoclonal
      antibody in the presence of selected sets of recombinant (r) human cytokines.
      Following this priming process the cytokine secretion profiles of the recovered T
      cells were assayed after restimulation, both at the population and single-cell
      levels. A marked shift towards T2 profile, characterized by heightened production
      of IL-4, IL-5 and IL-13, was obtained after priming in the presence of rIL-4
      alone. Addition of rIL-2 partially antagonized this effect. In contrast, priming
      in the presence of rIL-2 and rIL-12 induced a shift towards a T1 pattern
      characterized by increased productions of IFN-gamma and IL-2. Strikingly, the T2
      profile appeared more stable in culture than the T1 profile. We also observed
      that the CD4+ helper T cell subset was the major producer of T1 and T2 cytokines
      after restimulation. These results establish in vitro parameters to deliberately
      and reproducibly activate resting polyclonal T cells towards a defined and
      persistent cytokine secretion profile. Autologous T cells polarized under these
      conditions could be passively transferred as a therapeutic approach in diseases
      thought to result from imbalance between T1 and T2 responses.

PMID- 9521064
TI  - Expression of B220 on activated T cell blasts precedes apoptosis.
AB  - Superantigens are bacterial or viral products that polyclonally activate T cells
      bearing certain TCR beta chain variable elements. For instance, Vbeta8+ T cells
      proliferate in response to staphylococcal enterotoxin B (SEB) in vivo and then
      undergo Fas- and/or TNF-mediated apoptosis. We have recently shown that apoptotic
      SEB-reactive T cells express the B cell marker B220. Here we report the
      identification of a novel subset of CD4+ B220+ T cell blasts that are the
      precursors of these apoptotic cells in SEB-immunized mice. Moreover, we show that
      the CD4- CD8- B220+ T cells that accumulate in the lymphoid organs of Fas ligand
      defective gld mice stably express a form of the B220 molecule which exhibits
      biochemical similarities to that expressed by activated wild-type T cells, but is
      distinct from that displayed on the surface of B cells. Surprisingly, we also
      find a population of CD4+ B220+ pre-apoptotic T cells in FasL-defective gld mice,
      arguing that these cells can be generated in a Fas-independent fashion.
      Collectively, our data support a general model whereby upon activation, T cells
      up-regulate B220 before undergoing apoptosis. When the apoptotic mechanisms are
      defective, T cells presumably down-regulate their coreceptor molecules but retain
      expression of B220 as they accumulate in lymphoid organs.

PMID- 9521065
TI  - Regulation of cytoplasmic, surface and soluble forms of CD40 ligand in mouse B
      cells.
AB  - CD40 and CD40 ligand (CD40L) form one of most important receptor-ligand pairs
      that dock during T-B cell interactions as part of T-dependent antibody responses.
      It has been reported that among other cell types, B cells can express CD40L. Here
      we show that a large proportion of mouse B cells express CD40L in their
      cytoplasm, but not on the surface and that this is readily released as a soluble
      molecule. Thus, in their resting state up to 50% of mouse B cells express CD40L
      within their cytoplasm and both the proportion of cells expressing and the amount
      of CD40L is increased by signaling through immunoglobulin (Ig) or CD38. In
      contrast, T cell-derived signals such as CD40L (anti-CD40) or Th2-type cytokines
      cause a decrease in CD40L expression that is related to a release of a soluble
      form of the molecule from the cell. Supernatants from B cells activated with anti
      Ig and anti-CD40 contain CD40L in a variety of forms (18 kDa, 33 kDa and 66 kDa)
      that are readily detectable by immunoprecipitation with CD40-Fc gamma fusion
      protein (CD40-Ig) followed by Western blotting with anti-CD40L antibody (MR1).
      The 33-kDa species is distinct from the 39-kDa membrane-bound molecule found in
      activated T cells or in resting B cells and appears to be a novel soluble form of
      CD40L. Inhibition of T cell-independent in vitro stimulation of B cells with CD40
      Ig or anti-CD40L suggests that the B cell-derived soluble CD40L or CD40L
      expressed on the B cell surface can play a positive role in B cell proliferation.

PMID- 9521067
TI  - Antigen receptor-induced B lymphocyte apoptosis mediated via a protease of the
      caspase family.
AB  - An extensive body of data, in a variety of systems, denoted the caspase family of
      proteases as a key player in the execution of programmed cell death. This family
      consists of cysteine proteases that cleave after asparagine-containing motifs. It
      is well established that the caspases are essential for the apoptosis mediated by
      Fas (CD95) and TNF receptor p55, molecules that contain the "death domain" in the
      cytoplasmic tail. However, little is known about the mechanisms underlying the
      antigen receptor-mediated cell death in B lymphocytes, a process instrumental in
      negative selection of potentially autoreactive B cells. Here, we investigated the
      involvement of caspases in cell death triggered via the antigen receptor in B
      lymphocytes (BCR) by using specific inhibitors. Initially, we used a well
      established cell line, CH31, which is a model of B cell tolerance, to demonstrate
      that these proteases indeed participate in the BCR-induced apoptotic pathway.
      Next, we confirmed the physiological relevance of the caspase-mediated cell death
      pathway in splenic B cell populations isolated ex vivo that were induced to
      undergo apoptosis by extensive cross-linking of their BCR. Most interestingly,
      our data demonstrated that caspases regulate not only the nuclear DNA
      fragmentation, but also the surface membrane phosphatidylserine translocation as
      well as the degradation of a specific nuclear substrate. Taken together, this
      report supports the hypothesis that regulation of the caspase family is crucial
      in controlling the life/death decision in B lymphocytes mediated by the antigen
      receptor signal transduction.

PMID- 9521066
TI  - Constitutive expression of Bcl-xL or Bcl-2 prevents peptide antigen-induced T
      cell deletion but does not influence T cell homeostasis after a viral infection.
AB  - We examined the CD8+ T cell response to lymphocytic choriomeningitis virus (LCMV)
      in mice doubly transgenic for an LCMV-specific TCR and for either bcl-xL or bcl
      2. Clonal down-sizing of the anti-viral CD8+ T cell response and the generation
      of T cell memory was not influenced by constitutive expression of these anti
      apoptotic proteins in T cells. Expression of Bcl-xL or Bcl-2 did, however,
      prevent LCMV peptide-induced peripheral deletion of mature CD8+ T cells in vivo
      and apoptosis of activated LCMV-specific effector T cells in vitro. The CD8+ T
      cells "rescued" by Bcl-xL or Bcl-2 from peptide antigen-induced cell death were
      anergic and this could not be reversed by addition of IL-2 in vitro or by
      adoptive transfer into antigen-free recipient mice followed by LCMV infection in
      vivo. Taken together, we show here that 1) Bcl-xL or Bcl-2 are functionally
      equivalent in their ability to modulate CD8+ T cell survival in vivo, 2) distinct
      apoptosis signaling pathways exist in CD8+ T cells, one that can be inhibited by
      Bcl-2 or Bcl-xL and one that cannot be blocked, and 3) apoptosis of CD8+ effector
      T cells during the declining phase of an immune response is not prevented by
      constitutive expression of the anti-apoptotic proteins Bcl-xL and Bcl-2.

PMID- 9521068
TI  - Identification of the CC chemokines TARC and macrophage inflammatory protein-1
      beta as novel functional ligands for the CCR8 receptor.
AB  - Chemokines are key molecules in directing leukocyte migration toward sites of
      inflammation. We have previously cloned a putative CC chemokine receptor gene,
      TER1, whose expression is restricted to lymphoid tissues and cell lines.
      Recently, this receptor has been shown to signal in response to the human CC
      chemokine I-309 and thus it has been renamed CCR8 according to the current
      nomenclature. In the present study, we report the identification of the CC
      chemokines thymus and activation-regulated cytokine (TARC) and macrophage
      inflammatory protein-1 beta (MIP-1 beta) as CCR8 ligands, as they induce
      chemotaxis in CCR8 Jurkat stable transfectants. Furthermore, we have generated a
      polyclonal antiserum that is able to recognize the CCR8 molecule in transfectant
      lysates. The pattern of CCR8 mRNA expression and the functional effects exerted
      by its ligand suggest that the triggering of this receptor may regulate multiple
      functions including activation, migration and proliferation of lymphoid cells.

PMID- 9521069
TI  - Diminished expression of CD40 ligand may contribute to the defective humoral
      immunity in patients with MHC class II deficiency.
AB  - Major histocompatibility complex (MHC) class II deficiency (bare lymphocyte
      syndrome, BLS) is a rare primary immunodeficiency classified as a subgroup of
      severe combined immunodeficiency. We studied T and B lymphocyte function by
      examining the CD40 ligand/CD40 system in three BLS patients from two unrelated
      families. CD40 ligand expression by maximally activated BLS T cells was
      diminished. This abnormality may represent immunological naivete rather than a
      general T cell defect, since expression of activation marker CD69 and
      proliferative responses to PHA or anti-CD3 were normal, and BLS T cells primed
      and restimulated in vitro expressed normal amounts of CD40 ligand. BLS B cells
      proliferated and produced IgE if stimulated with anti-CD40 or soluble CD40 ligand
      and IL-4. Activation of BLS B cells with soluble CD40 ligand and IL-4 induced
      normal expression of activation markers, although MHC class II expression
      remained absent. Depressed antibody titers, lack of amplification and failure to
      undergo isotype switching in response to immunization with bacteriophage phi x
      174 demonstrated defective T cell help. We conclude that BLS B cells are
      functionally normal if appropriately stimulated, and that the defective humoral
      immunity observed may be related to diminished expression of CD40 ligand on BLS T
      cells.

PMID- 9521070
TI  - Signaling through human killer cell activating receptors triggers tyrosine
      phosphorylation of an associated protein complex.
AB  - Our understanding of the biology of human natural killer (NK) cells has
      significantly advanced in recent years upon identification of a family of NK cell
      expressed genes that encode killer cell inhibitory receptors (KIR). Individual
      KIR can selectively bind various HLA class I allotypes and consequently transduce
      inhibitory signals that block NK cell lysis of ligand-bearing target cells. A
      distinct subset of related and linked genes express truncated versions of KIR
      that are otherwise highly homologous in amino acid sequence. Interestingly, these
      receptors appear to transmit stimulatory signals into NK cells and have been
      termed killer cell activating receptors (KAR). In this report, we demonstrate
      that recognition of HLA-Cw3 by the p50 KAR, NKAT8, can potentiate the cytotoxic
      response of appropriate NK cell clones. Specific cross-linking of this KAR with a
      monoclonal antibody resulted in intracellular calcium mobilization, protein
      tyrosine phosphorylation, and phosphorylation of the MAP kinases, ERK1 and ERK2.
      In addition, we identified a KAR-associated disulfide-linked dimer of a 13-kDa
      protein that was absent in the Jurkat T cell line and is predicted to participate
      in these activation signaling events. Upon treatment of NK cells with
      pervanadate, the disulfide-linked p13 and additional proteins of 25, 30, 37 and
      50-95 kDa were identified as KAR-associated tyrosine phosphoproteins.
      Importantly, p13 was inducibly tyrosine phosphorylated upon cross-linking of
      NKAT8, which strongly suggests that the associated p13 provides KAR with
      appropriate cytoplasmic structure to couple with tyrosine kinase-mediated
      signaling effectors.

PMID- 9521071
TI  - Gene transfer with IL-4 and IL-13 improves survival in lethal endotoxemia in the
      mouse and ameliorates peritoneal macrophages immune competence.
AB  - Systemic anti-cytokine therapies have been unsuccessful in preventing mortality
      from gram-negative bacteremia in humans partly because of the failure to
      neutralize pro-inflammatory cytokines at sites of exaggerated production. In an
      attempt to deliver anti-inflammatory cytokines to organs directly, gene transfer
      was employed. Thirty-six BALB/c mice were injected intraperitoneally with
      cationic liposomes containing plasmids encoding the human interleukin-4 (hIL-4)
      or IL-13 gene. Both, hIL-4 and hIL-13 mRNA were detected by reverse transcription
      polymerase chain reaction analysis in the liver and the spleen of the animals.
      Fourty-eight hours after the in vivo gene transfer, these 36 mice and 18 mock
      transfected mice, were challenged with a lethal dose of E. coli
      lipopolysaccharide with D-galactosamine (D-GalN). Gene transfer with hIL-4
      reduced the serum tumor necrosis factor (TNF)-alpha production in response to
      endotoxin/D-GalN by 80% from 113.1 pg/ml in mock-transfected animals to 22.2
      pg/ml (p < 0.05); human IL-13 gene transfer reduced serum TNF-alpha levels by 90%
      (113.1 pg/ml to 11.6 pg/ml; p < 0.05). Survival was improved from 20% to over 83%
      in both treatment groups (p < 0.001). Our data demonstrate a potent in vivo anti
      inflammatory action of both IL-4 and IL-13. In addition, the immune functions of
      peritoneal macrophages are significantly ameliorated in both treatment groups,
      with IL-13 demonstrating better macrophage immune modulation than IL-4 (p <
      0.05).

PMID- 9521072
TI  - Modulation of the anti-acetylcholine receptor response and experimental
      autoimmune myasthenia gravis by recombinant fragments of the acetylcholine
      receptor.
AB  - Myasthenia gravis (MG) is a neuromuscular disorder of man caused by a humoral
      response to the acetylcholine receptor (AChR). Most of the antibodies in MG and
      in experimental autoimmune myasthenia gravis (EAMG) are directed to the
      extracellular portion of the AChR alpha subunit, and within it, primarily to the
      main immunogenic region (MIR). We have cloned and expressed recombinant
      fragments, corresponding to the entire extracellular domain of the AChR alpha
      subunit (H alpha1-210), and to portions of it that encompass either the MIR (H
      alpha1-121) or the ligand binding site of AChR (H alpha122-210), and studied
      their ability to interfere with the immunopathological anti-AChR response in
      vitro and in vivo. All fragments were expressed as fusion proteins with
      glutathione S-transferase. Fragments H alpha1-121 and H alpha1-210 protected AChR
      in TE671 cells against accelerated degradation induced by the anti-MIR monoclonal
      antibody (mAb)198 in a dose-dependent manner. Moreover, these fragments had a
      similar effect on the antigenic modulation of AChR by other anti-MIR mAb and by
      polyclonal rat anti-AChR antibodies. Fragments H alpha1-121 and H alpha1-210 were
      also able to modulate in vivo muscle AChR loss and development of clinical
      symptoms of EAMG, passively transferred to rats by mAb 198. Fragment H alpha122
      210 did not have such a protective activity. Our results suggest that the
      appropriate recombinant fragments of the human AChR may be employed in the future
      for antigen-specific therapy of myasthenia.

PMID- 9521073
TI  - Differential processing of influenza nucleoprotein in human and mouse cells.
AB  - To investigate how early events in antigen processing affect the repertoire of
      peptides presented by MHC class I molecules, we compared the presentation of the
      influenza A nucleoprotein epitope 265-273 by HLA-A3 class I molecules in human
      and mouse cells. Mouse cells that express HLA-A3 failed to present the NP265-273
      peptide when contained within the full-length nucleoprotein, to HLA-A3-restricted
      human cytotoxic T lymphocytes. However, when the epitope was generated directly
      in the cytosol using a recombinant vaccinia virus that expressed the nonamer
      peptide, mouse cells were recognized by HLA-A3-restricted CTL. Poor transport of
      the peptide by mouse TAP was not responsible for the defect as co-infection of
      mouse cells with recombinant vaccinia viruses encoding the full-length
      nucleoprotein and the human TAP1 and TAP2 peptide transporter complex failed to
      restore presentation. These results therefore demonstrate a differential
      processing of the influenza nucleoprotein in mouse and human cells. This
      polymorphism influences the repertoire of peptides presented by MHC class I
      molecules at the cell surface.

PMID- 9521074
TI  - A novel 90-kDa tyrosine-phosphorylated protein associated with TCR complex in
      thymocytes.
AB  - Ligation of the TCR-CD3 complex initiates a cascade of tyrosine phosphorylation
      that results in T cell activation. Initial activation of tyrosine kinases depends
      on the phosphorylation of activation motifs on CD3 chains. We previously found
      that a 90-kDa protein was tyrosine phosphorylated upon TCR cross-linking and the
      induction of the phosphorylation was dependent on the structure of the CD3
      complex. In this study, we further characterized p90 phosphorylation.
      Phosphorylation of p90 was induced only by stimulation through the TCR-CD3
      complex but not by other kinds of stimulation including CD28- or hydrogen
      peroxide-mediated activation and was dynamically regulated. Phosphorylated p90
      was associated with the TCR-CD3 complex upon T cell activation. In a normal T
      cell population, thymocytes but not splenic T cells induced the tyrosine
      phosphorylation of p90 upon TCR cross-linking. These results suggest that p90 is
      a novel phosphoprotein associated with the TCR-CD3 complex and may play a role in
      TCR signaling during thymocyte differentiation.

PMID- 9521075
TI  - CD40 ligand and IFN-gamma synergistically restore IL-12 production in HIV
      infected patients.
AB  - IL-12 production in HIV-infected (HIV+) individuals is severely impaired after
      stimulation by bacterial products or T cell-dependent stimuli. Because CD40-CD40
      ligand (CD40L) interactions are the major mechanism involved in the T cell
      dependent activation of antigen-presenting cells, we investigated whether this
      pathway was functional in HIV+ donors. CD40 expression was increased on freshly
      isolated monocytes from HIV+ individuals compared to HIV donors. However,
      equivalent CD40 expression was obtained in the two groups after cytokine
      stimulation. Since CD40 expression was intact in HIV+ donors' cells, we
      determined whether IL-12 production could be restored by providing exogenous T
      cell-dependent stimuli, CD40L and IFN-gamma, at the time of bacterial
      stimulation. IL-12 production was not altered by CD40L alone, was increased by
      IFN-gamma, and was synergistically restored to normal values by IFN-gamma +
      CD40L. This combination was more efficient for enhancing IL-12 production than
      granulocyte-macrophage colony-stimulating factor + CD40L or neutralizing anti-IL
      10 antibody + CD40L. CD40L did not affect IL-10 production, whereas IFN-gamma
      significantly decreased it. This study demonstrates that the defect in IL-12
      production by leukocytes from HIV+ donors can be overcome in vitro if the
      interacting cells are provided with the right T cell-dependent co-stimuli.

PMID- 9521076
TI  - Comparable impact of mutational and selective influences in shaping the expressed
      repertoire of peripheral IgM+/CD5- and IgM+/CD5+ B cells.
AB  - Somatic hypermutation and subsequent selection play a significant role in shaping
      the peripheral B cell repertoire. This repertoire is composed of CD5+ (5%) and
      CD5- B cells (95%) which are known to traffic through different lymphoid
      compartments. Previous studies have shown that V(H) gene usage by CD5+ and CD5- B
      cells is similar, although mutations are more frequent in the latter. However,
      the effect of mutation and subsequent selection on the expressed V(H) repertoire
      of CD5+ and CD5- B cells has not been delineated in detail. This study,
      therefore, analyzed the mutational pattern of individual IgM+/CD5+ and IgM+/CD5-
      B cells. In both populations, mutations can occur without heavy chain isotype
      switching. Despite the differences in mutational frequency, the patterns of
      mutation and subsequent selection were comparable in CD5+ and CD5- B cells. These
      results imply that although mutations are more frequent in CD5- B cells, the
      overall mechanisms governing somatic hypermutation and subsequent positive and
      negative selection are similar in CD5+ and CD5- B cells.

PMID- 9521077
TI  - Neutralization of IL-12 demonstrates the existence of discrete organ-specific
      phases in the control of Leishmania donovani.
AB  - IL-12 plays a key role in stimulating both innate and antigen-specific immune
      responses against a number of intracellular pathogens. A neutralizing anti-IL-12
      monoclonal antibody (mAb) was used to define and compare the role of endogenous
      IL-12 in the liver and spleen of mice infected with Leishmania donovani. IL-12
      neutralization both early and late in infection caused delayed resolution of
      parasite load, a transient decrease in IFN-gamma, IL-4, TNF-alpha and inducible
      nitric oxide synthase (NOS-2) production, and suppressed tissue granuloma
      formation in the liver of genetically susceptible BALB/c mice. In contrast to the
      liver of BALB/c mice, neutralization of IL-12 had no effect on parasite burden in
      the spleen over the first 28 days of infection. However, IL-12 appeared to be
      critical for the development of mechanisms which subsequently contain the growth
      of persistent parasites in this organ in that neutralization of IL-12
      dramatically enhanced parasite growth after day 28 of infection. Following IL-12
      neutralization, the later unchecked growth of parasites in the spleen was
      coincident with an extensive breakdown of the tissue microarchitecture.
      Immunohistochemical studies revealed that IL-12 was largely produced by
      uninfected cells in L. donovani-infected BALB/c mice. In contrast, the course of
      infection in the liver and spleen of genetically resistant CBA/n mice was
      unaffected by the administration of anti-IL-12 mAb. These results suggest that
      the liver and spleen in susceptible BALB/c mice have different temporal
      requirements for IL-12 in controlling L. donovani infection, whereas IL-12 plays
      little role in either organ in resistant CBA/n mice. In addition, IL-12 appears
      to be involved in the generation of both Th1 and Th2 responses during L. donovani
      infection in BALB/c mice.

PMID- 9521078
TI  - Antigen dose-dependent differences in IgE antibody production are not due to
      polarization towards Th1 and Th2 cell subsets.
AB  - The quality of the humoral immune response against protein antigens in CBA/J mice
      is dependent on the antigen dose used for immunization: low doses induce high
      titers of IgE antibodies, whereas high doses promote the production of IgG2a
      antibodies but inhibit IgE formation. To investigate whether the reciprocal
      regulation of antibody production is possibly due to a differential activation of
      Th1 and Th2 cell populations in the two immunization groups, the cytokine pattern
      of spleen cells from both groups, cultured with antigen in vitro, was analyzed by
      measurement of intracellular and secreted cytokine levels. The data presented
      show that in vitro restimulated spleen cells from mice primed with low as well as
      with high doses of antigen produce predominantly the Th2 cytokines IL-4 and IL-10
      but reduced levels of IL-12. The release of IFN-gamma is only slightly enhanced
      compared to unstimulated control cultures. The results indicate that CD4+ T cells
      in both groups belong mainly to the Th2 cell subset. This finding is
      contradictory to the general allegation that the antigen dose is decisive for the
      polarization of Th1 versus Th2 immune responses and shows that the antigen dose
      dependent regulation of IgE antibody production is not due to differential
      polarization towards Th1 and Th2 cells.

PMID- 9521079
TI  - Dendritic cells, but not macrophages, produce IL-12 immediately following
      Leishmania donovani infection.
AB  - Infection with Leishmania, an obligate intracellular parasite of mononuclear
      phagocytes, stimulates the production of IFN-gamma from NK cells, via a pathway
      which is dependent upon IL-12 and IL-2. IL-12 is also essential for the
      development of host protective T cell responses to this parasite. However,
      previous in vitro studies have indicated that macrophages fail to make IL-12
      following infection with Leishmania, and that subsequent to infection,
      macrophages become refractory to normal IL-12-inducing stimuli. We have used an
      in situ approach to attempt to resolve this apparent paradox, and by
      immunostaining for IL-12 p40 protein, we now demonstrate for the first time, that
      dendritic cells (DC) are the critical source of early IL-12 production following
      Leishmania infection. IL-12 production by DC is transient, peaking at 1 day post
      infection and returning to the levels seen in uninfected mice by day 3. Although
      resident tissue macrophages fail to produce IL-12 after Leishmania infection,
      these cells are not totally refractory to cytokine inducing stimuli, as TNF-alpha
      production is induced by day 3 post infection. Not only do these data
      satisfactorily explain the differences between in vivo and in vitro data by
      identifying the cellular source of IL-12, but they also suggest a novel model for
      NK cell activation; namely that in response to pathogens which fail to trigger IL
      12 production by macrophages, DC-T cell clusters provide the microenvironment for
      initial NK cell activation.

PMID- 9521081
TI  - Human lung mast cells are enriched in the capacity to produce granulocyte
      macrophage colony-stimulating factor in response to IgE-dependent stimulation.
AB  - By using reverse transcription-PCR, in situ hybridization, enzyme-linked
      immunosorbent assay and immunocytochemistry, we have studied the production of
      granulocyte-macrophage colony-stimulating factor (GM-CSF) in human lung mast
      cells induced by cross-linkage of high-affinity Fc epsilon receptors (Fc
      epsilonRI). We have also confirmed the bioactivity of GM-CSF released from lung
      mast cells by investigating the effect of the supernatant from lung mast cells
      activated with anti-IgE on the release of eosinophil cationic protein (ECP) from
      eosinophils. Mast cells were purified using affinity magnetic selection with
      monoclonal antibody (mAb) YB5.B8 (93-99% pure). Purified mast cells were
      precultured with IgE for 16 h before challenge with 1 microg/ml anti-IgE with or
      without stem cell factor (SCF). Eosinophils were purified by immunomagnetic
      negative selection (> 98% pure). The activation of mast cells via Fc epsilonRI
      enhanced the intensity of the GM-CSF signal within 2 h and the cells produced GM
      CSF protein 4 h after the activation. In the absence of recombinant human (rh)
      SCF, anti-IgE induced a median GM-CSF response of 202 (< 15 to approximately 681)
      pg/10(6) mast cells/24 h, whereas in the presence of rhSCF the median IgE
      dependent GM-CSF release was 356 (152 to approximately 1216) pg/10(6) mast
      cells/24 h. This difference was statistically significant (p = 0.0029, n = 12).
      In contrast, mast cells produced only a small amount of GM-CSF in the absence of
      anti-IgE. The mast cell supernatant induced ECP release from eosinophils and the
      release was significantly inhibited by blocking mAb against GM-CSF. These
      findings indicate that human mast cells are an important cellular source of GM
      CSF and as such may contribute to chronic eosinophil-mediated inflammation.

PMID- 9521080
TI  - A T cell activation antigen, Ly6C, induced on CD4+ Th1 cells mediates an
      inhibitory signal for secretion of IL-2 and proliferation in peripheral immune
      responses.
AB  - A T cell activation antigen, Ly6C, is considered to be involved in the
      autoimmunity of some autoimmune-prone mice; however, the function of Ly6C remains
      largely unknown. We prepared a rat anti-mouse Ly6C monoclonal antibody (mAb)
      (S14) that inhibits the proliferation of peripheral T cells stimulated with anti
      CD3 mAb in vitro. S14 mAb, the specificity of which is confirmed by a cDNA
      transfectant, recognizes Ly6C antigen preferentially expressed on a part of CD8+
      T cells in peripheral lymphoid organs. The immunohistochemical analysis
      demonstrates that Ly6C appears on CD8+ T cells in the conventional T cell
      associated area of BALB/c but not of nonobese diabetic (NOD) mice, confirming the
      absence of Ly6C+ T cells in NOD mice. Addition of soluble S14 mAb to the culture
      does not influence the proliferation of T cells in vitro; however, the S14 mAb
      coated on the plate clearly inhibits the proliferation and IL-2 production of
      anti-CD3-stimulated peripheral T cells. The T cells are arrested at the
      transitional stage from G0/G1 to S+G2/M phases, but they are not induced to
      undergo apoptotic changes in vitro. This inhibitory signal provided through the
      Ly6C molecule inhibited IL-2 secretion in a subpopulation of the activated CD4+ T
      cells. Ly6C is expressed on T cell clones of both Th1 and Th2 cells, but the
      cytokine secretion from Th1 clones is preferentially inhibited. These results
      suggest that Ly6C mediates an inhibitory signal for secretion of cytokines from
      Th1 CD4+ T cells, potentially causing the inhibition of immune response in
      peripheral lymphoid tissues.

PMID- 9521082
TI  - Imaging antigen recognition by naive CD4+ T cells: compulsory cytoskeletal
      alterations for the triggering of an intracellular calcium response.
AB  - Antigen recognition was analyzed at the single-cell level by using for the first
      time T cells which were not altered by in vitro selection, transfection or
      immortalization. The first consequence of antigen recognition by ex vivo naive
      CD4+ T cells from T cell receptor (TCR)-transgenic mice is the formation of a
      "contact zone" with the B cell presenting the antigen. The T cell intracellular
      calcium (Ca2+) response begins after a delay of 30 s on average, following the
      formation of the contact zone. The T cell response is entirely inhibited by
      either protein tyrosine kinase or actin polymerization inhibitors but,
      surprisingly, it is insensitive to inhibitors of phosphoinositide 3-kinase.
      Moreover, inhibition of microtubule polymerization and use of Ca2+-free medium do
      not prevent the beginning of the T cell response, but do reduce the stability of
      the contact zone and/or the amplitude of the Ca2+ plateau. The critical
      involvement of the cytoskeleton in antigen recognition on B cells introduces a
      checkpoint in T cell activation: the initial TCR engagement triggers a Ca2+
      response only after an amplification step corresponding to a cytoskeleton
      controlled increase in the number of engaged TCR.

PMID- 9521083
TI  - Small bowel enteropathy: role of intraepithelial lymphocytes and of cytokines (IL
      12, IFN-gamma, TNF) in the induction of epithelial cell death and renewal.
AB  - The small bowel mucosa contains within its villus epithelium a large number of
      intraepithelial lymphocytes (IEL) which upon activation are cytotoxic and release
      large quantities of IFN-gamma and TNF; these activities are increased by in vitro
      exposure to IL-12. Mice injected with IL-12 develop severe damage of the villus
      epithelial cells, in form of apoptosis, necrosis and a third distinct form of
      cell death, characterized ultrastructurally by progressive cell shrinkage. These
      lesions are accompanied by a compensatory acceleration of the epithelial renewal,
      a hallmark of epithelial injury. Use of a variety of mutant mice showed that
      these lesions require the presence of IEL (all populations being involved, thymus
      dependent as well as natural killer-T cell IEL) and the release of IFN-gamma. The
      critical role of IFN-gamma may result in part from its capacity to induce on
      epithelial cells the expression of target molecules involved in the different
      cytotoxic pathways used by IEL. However, injection of IFN-gamma into mutant mice
      lacking IEL showed that IFN-gamma can directly induce villus epithelial damage as
      well. On the other hand, injection of TNF induces fulminant apoptosis of villus
      epithelial cells, starting at the top of the villi; however TNF is not required
      for IL-12-induced enteropathy, which is unmodified in mutant mice lacking TNF. We
      propose that, when activated by their cognate ligands and/or IL-12 produced by
      cells in the lamina propria, IEL eliminate infected and senescent epithelial
      cells through a combination of cytotoxicity and of IFN-gamma and TNF release.
      This insures the rapid epithelial renewal of the villi, which in turn helps
      maintain the functional integrity of the barrier.

PMID- 9521084
TI  - Co-capping studies reveal CD8/TCR interactions after capping CD8 beta
      polypeptides and intracellular associations of CD8 with p56(lck).
AB  - CD8 is a T cell surface glycoprotein that participates in recognition of
      peptide/MHC class I molecules by binding to their alpha 3 domains. In addition,
      the cytoplasmic domain of CD8 associates with the intracellular tyrosine kinase
      p56(lck) (lck) promoting recruitment of lck to the TCR signaling complex. Recent
      data have suggested also that CD8 may interact with the TCR to promote
      energetically favorable conformations which increase its ligand binding. We have
      used the techniques of co-capping and confocal microscopy to ask whether we can
      detect an association between CD8 and the TCR independently of their binding to
      MHC class I molecules. We show that capping CD8 heterodimers with antibodies to
      the CD8 beta polypeptide is significantly more efficient than antibodies to the
      CD8 alpha polypeptide at inducing co-localization of TCR molecules with CD8,
      suggesting that there may be preferred conformations of CD8 which stabilize
      interactions with the TCR. In addition, we show by microscopy that intracellular
      lck redistributes very efficiently to the area of a CD8 cap, suggesting that
      there is a stronger association between lck and CD8 than has been proposed from
      immunoprecipitation analyses.

PMID- 9521086
TI  - Ocular oxidants and antioxidant protection.
AB  - Oxidative damage and antioxidant protection in ocular tissues has not been
      reviewed recently. Metabolism in the eye is of increasing interest because the
      organ is highly susceptible to damage by sunlight, oxygen, various chemicals, and
      pollutants. Interest is expected to increase because of an aging Western world
      population and a continued depletion of stratospheric ozone. Hydrogen peroxide is
      discussed because it is both a byproduct and a source of free radical reactions
      and is normally present in the aqueous humor. The metabolism of reactive oxygen
      species by enzymes, nutrients, pigments, and low molecular weight scavengers is
      evaluated. Ascorbic acid, because of its high concentration in the eye, is
      thought to be a primary substrate in ocular protection; progress in determining
      the mechanisms by which it is recycled and maintained in the useful, reduced
      state is discussed. Recent information is included about antioxidants not
      previously known to be present in the eye, and some importance is placed on the
      properties of the vitreous humor and tear fluid because of the previous lack of
      emphasis on these.

PMID- 9521085
TI  - The structural basis of MHC control of collagen-induced arthritis; binding of the
      immunodominant type II collagen 256-270 glycopeptide to H-2Aq and H-2Ap
      molecules.
AB  - The Aq major histocompatibility complex (MHC) class II molecule is associated
      with susceptibility to murine collagen-induced arthritis (CIA), whereas the
      closely related H-2Ap molecule is not. To understand the molecular basis for this
      difference, we have analyzed the ability of H-2Aq and H-2Ap molecules (referred
      to as Aq and Ap) to bind and present collagen type II (CII)-derived glycosylated
      and non-glycosylated peptides. T cell clones specific for the immunodominant CII
      256-270 peptide and restricted to both Aq and Ap molecules were identified. When
      these clones were incubated with CII protein and either Aq- or Ap-expressing
      antigen-presenting cells (APC), only Aq-expressing APC were able to induce
      stimulation. With the use of A(beta) transgenic mice this could be shown to be
      solely dependent on the MHC class II molecule itself and to be independent of
      other MHC- or non-MHC genes. Peptide binding studies were performed using
      affinity-purified MHC class II molecules. The CII 256-270 peptide bound with
      lower affinity to the Ap molecule than to the Aq molecule. Using a set of alanine
      substituted CII 256-270 peptides, MHC class II and T cell receptor (TCR) contacts
      were identified. Mainly the side chains of isoleucine 260 and phenylalanine 263
      were used for binding both the Aq and Ap molecule, i.e. the peptide was
      orientated similarly in the binding clefts. The major TCR contact amino acids
      were lysine 264, which can be posttranslationally modified, and glutamic acid
      266, which is the only amino acid in the heterologous peptide which differs from
      the mouse sequence. Glycosylation at positions 264 and 270 of the CII 256-270
      peptide did not change the anchor positions used for binding to the Aq or Ap
      molecules. The autologous form of the peptide (with aspartic acid at position
      266) bound with lower affinity to the Aq molecule as compared with the
      heterologous peptide. The variable affinity displayed by the immunodominant CII
      256-270 peptide for different MHC class II molecules, the identification of MHC
      and TCR contacts and the significance of glycosylation of these have important
      implications for the understanding of the molecular basis for inherited MHC class
      II-associated susceptibility to CIA and in turn, for development of novel
      treatment strategies in this disease.

PMID- 9521087
TI  - Prolactin in autoimmune diseases.
AB  - The immune system is still regarded by many as autonomous, and prolactin (Prl)
      has traditionally been considered as a lactogenic hormone. Over the last 10
      years, the total number of publications considering Prl is decreasing, while the
      number of those investigating its role in immunity sustainly increased. In
      addition to the pituitary gland, Prl-like peptides can be produced by activated
      leukocytes and fibroblasts. Elevated serum levels of Prl in (rat) adjuvant
      arthritis, (murine) collagen type II-induced arthritis, (murine and human)
      systemic lupus erythematosus (SLE), and (murine and rat) autoimmune type I
      diabetes may influence the outcome of the disease. It is suggested that mild
      hyperprolactinemia is a risk factor for the development of autoimmunity. This can
      occur under certain circumstances, for example adrenocortical deficiency or
      postpartum. In human SLE, Prl appears to favor the production of anti-double
      stranded DNA. While glucocorticoids would damp the immune reactivity, Prl
      constitutes a stimulatory link between the neuroendocrine and immune systems.
      Future directions should include: 1) multicenter projects for evaluation of the
      therapy with Prl-inhibiting compounds in SLE, considering for example the HLA
      DRB1 *0301 status; and 2) the regulation of extra-pituitary Prl-like cytokines
      ("proliferins") (e.g., in rheumatoid arthritis synovium) and their role in the
      production of catabolic enzymes.

PMID- 9521088
TI  - The hsp90-based chaperone system: involvement in signal transduction from a
      variety of hormone and growth factor receptors.
AB  - A variety of transcription factors and protein kinases involved in signal
      transduction are recovered from cells in heterocomplexes containing the abundant
      protein chaperone hsp90. Genetic studies in yeast have demonstrated that binding
      of steroid receptors, the dioxin receptor, and some protein kinases to hsp90 is
      critical for their signal transducing function in vivo. These heterocomplexes are
      formed by a multiprotein chaperone machinery consisting of at least four
      ubiquitous proteins--hsp90, hsp70, p60 and p23. Four high-molecular-weight
      immunophilins have been discovered as components of steroid receptor or other
      transcription factor complexes with hsp90. The immunophilins, protein chaperones
      with prolyl isomerase activity, bind the immunosuppressant drugs FK506 or CyP-40.
      These immunophilins all bind via tetratricopeptide repeat (TPR) domains to a
      single TPR binding site on each hsp90 dimer, and multiple heterocomplexes exist
      for each protein chaperoned by hsp90 according to the immunophilin that is bound
      to this TPR binding site at any time. Three components of the MAP kinase
      signalling system (Src, Raf, and Mek) exist in complexes with hsp90 and a 50-kDa
      protein that is the mammalian homolog of the yeast cell cycle control protein
      cdc37. The p50cdc37 binds to hsp90 at a site that is close to but different from
      the TPR binding site of the immunophilins, and like the immunophilins, p50cdc37
      is thought to be involved in targeting and trafficking of the protein kinases.
      The recent introduction of the benzoquinone antibiotic geldanamycin has
      facilitated the identification of proteins that are chaperoned by the hsp90-based
      system. Geldanamycin binds to members of the hsp90 protein family, blocking
      assembly of hsp90 heterocomplexes and destabilizing preformed heterocomplexes. In
      the presence of geldanamycin, the function of hsp90-chaperoned proteins is
      disrupted, and the proteins undergo rapid degradation by an ubiquitin-dependent
      proteasomal mechanism. It is becoming clear that hsp90 chaperoning is not only
      essential to a variety of signal transduction pathways, but is critical for
      proper folding, stabilization, and trafficking of an expanding list of proteins.

PMID- 9521089
TI  - Pyrogenicity of etiocholanolone and interleukin-1 in New and Old World Monkeys.
AB  - Etiocholanolone (5beta-androstan-3alpha-ol-17-one; designated E) is one of the
      major products of metabolism of testosterone and androstenedione (androst-4-ene
      3,17-dione) in many mammalian species, including humans. E and several other
      5beta-reduced steroids have been found to induce fever in humans. The pyrogenic
      effect of these steroids has been shown to be due to the release of interleukin-1
      (IL-1) from the leukocytes that are mobilized in response to the steroid
      injections. Old World Monkeys such as Rhesus monkeys (Macaca mu/atta), metabolize
      androgens similarly to humans, and E is a normal metabolite. However, New World
      Monkeys such as Squirrel monkeys (Saimiri sciureus), lack hepatic 5alpha- and
      5beta-steroid reductases and excrete androgens primarily in an unaltered state; E
      is not produced. Therefore, we postulate that Squirrel monkeys likewise may have
      lost the ability to respond to 17-ketosteroids such as E. To test this
      hypothesis, adult male Rhesus and Squirrel monkeys were treated with E, and their
      rectal temperatures were recorded over a 24-hr period. Rhesus monkeys exhibited a
      rise of up to 3 degrees F following E injection. Squirrel monkeys, on the other
      hand, did not exhibit any increase in rectal temperature over the 24-hr period,
      even when doses up to 250 times the effective human dose were used. However, both
      species responded to injected IL-1alpha with a robust increase in rectal
      temperature. The data show that E is pyrogenic in Rhesus, but not Squirrel
      monkeys. The findings support the notion that injected E may induce release of IL
      1 in Rhesus monkeys, but not in Squirrel monkeys.

PMID- 9521090
TI  - Regulation of 10P2 murine mast cell proliferation and secretory function by stem
      cell factor or IL-9.
AB  - Mast cells are effectors of inflammatory responses. When triggered by
      immunological or nonimmunological mechanisms, mast cells release potent
      biological mediators from preformed stores and synthesize others de novo. In
      previous investigations from this laboratory, the signal transduction pathways of
      cloned 10P2 cytokine-independent mast cells were explored. Results suggested that
      10P2 cells undergo activation-secretion coupling assessed as release of stored
      [14C]serotonin (5-HT) when challenged with IgE-specific antigen, influx of
      extracellular calcium, release of intracellular calcium stores, or by direct
      activation of protein kinase C isozymes. In the present investigations, cytokine
      proliferative effects and modulatory roles on release of stored [14C]5-HT have
      been explored. Following passive sensitization with anti-dinitrophenol (anti-DNP)
      IgE and challenge with DNP, mast cells released up to 32% of the stored [14C]5
      HT. Pretreatment of cells with 10, 30, or 50 ng/ml stem cell factor (SCF) did not
      alter the response. SCF did not directly induce [14C]5-HT release. Pretreatment
      with 25 ng/ml interleukin-9 (IL-9) significantly potentiated the IgE-antigen
      release by 51.1%, 35.7%, or 31.6% when challenged with 3, 10 or 30 ng/ml DNP-HSA.
      Treatment of cells with 1-100 ng/ml SCF for 72 hr resulted in significantly
      enhanced proliferation whereas this did not occur when cells were treated with 1
      100 ng/ml IL-9. Collectively, these results suggest that SCF alone has a
      proliferative effect, does not alter the IgE-specific antigen signal transduction
      pathway, and does not directly stimulate mast cell degranulation. In contrast, IL
      9 potentiates the IgE-antigen signal transduction response but exerts no
      proliferative response. Reports of effects of orally administered cytokines are
      now beginning to emerge. This raises the possibility that cytokines may be a
      future therapeutic approach to treatment of allergic and nonallergic inflammatory
      diseases. The 10P2 cytokine-independent mast cell line may be a valuable adjunct
      to existing mast cell models as this avenue of drug discovery is explored.

PMID- 9521091
TI  - Effect of stage of development and sex on gonadotropin-releasing hormone
      secretion in in vitro hypothalamic perifusion.
AB  - Marked sexual and ontogenic differences have been described in gonadotropin
      regulation in the rat. These could arise from events occurring both at the
      hypothalamic or hypophyseal levels. The present experiments were designed to
      evaluate the capacity of the hypothalamus in releasing GnRH in vitro, basally and
      in response to depolarization with KCl, during ontogeny in the rat. To that end
      we chose two well-defined developmental ages that differ markedly in sexual and
      ontogenic characteristics of gonadotropin regulation, 15 and 30 days. We compared
      GnRH release from hypothalami of females, neonatal androgenized females and
      males. Mediobasal hypothalami were perifused in vitro, and GnRH measured in the
      effluent. Basal secretion of the decapeptide increased with age in the three
      groups with no sexual differences encountered. When studying GnRH release induced
      by membrane depolarization, no differences within sex or age were encountered. On
      the other hand FSH serum levels decreased with age in females and increased in
      males, and in neonatal androgenized females followed a similar pattern to that of
      females. LH levels were higher in infantile females than in age-matched males or
      androgenized females. Such patterns of gonadotropin release were therefore not
      correlated to either basal or K+-induced GnRH release from the hypothalamus. We
      conclude that sexual and ontogenic differences in gonadotropin secretion in the
      developing rat are not dependent on the intrinsic capability of the hypothalamus
      to release GnRH in response to membrane depolarization. The hormonal differences
      observed during development and between sexes are probably related to differences
      in the sensitivity of the GnRH neuron to specific secretagogue and
      neurotransmitter regulation, and/or to differences in hypophyseal GnRH receptors
      and gonadotrope sensitivity.

PMID- 9521092
TI  - The dominant role of CPP32 subfamily in fas-mediated hepatitis.
AB  - Fas is a cell surface molecule that transduces the apoptotic death signaling on
      the stimulation of Fas ligand, and plays the dominant role in various disease
      states. The lethal effect of Fas antibody in mice has been reported, and this
      experimental procedure has been used as the model for hepatitis. Recently, the
      prevention of this Fas antibody-induced hepatitis by the broad caspase inhibitor
      (z-VAD.fmk) has been reported. In the present study, we additionally demonstrated
      that the CPP32 subfamily, rather than the ICE subfamily, plays the dominant role
      in the Fas antibody-induced hepatitis. Fas antibody-injection induced chromosomal
      DNA fragmentation and CPP32 subfamily-activation in both the liver and lung.
      Tissue damage observed in the lung was weak as compared with liver damage. When
      mice were exposed to DEVD-CHO (specific inhibitor of CPP32 subfamily), this
      lethal effect of Fas antibody, tissue destruction, and CPP32 subfamily-activation
      were prevented. In contrast, YVAD-CHO (specific inhibitor of ICE subfamily) could
      not prevent the lethal effect of Fas antibody. We propose here that the CPP32
      subfamily plays the dominant role in Fas-mediated hepatitis, and DEVD-CHO would
      be an effective cure for hepatitis.

PMID- 9521094
TI  - Effects of chronic hyperprolactinemia on tuberoinfundibular dopaminergic neurons.
AB  - Prolactin (PRL) secretion is under the inhibitory regulation of the
      tuberoinfundibular dopaminergic (TIDA) system. Short-term elevation in PRL levels
      has been shown to increase the activity of TIDA neurons, however, the
      responsiveness of TIDA neurons to chronically elevated serum PRL levels is
      controversial. The purpose of this study was to investigate the effects of
      prolonged elevations of serum PRL on TIDA neuronal activity. Female Sprague
      Dawley rats (2-3 months old) were ovariectomized and implanted (s.c.) with
      haloperidol (HAL), a dopamine receptor antagonist for 6 or 9 months to produce
      hyperprolactinemia. Ovariectomized, sham-implanted rats were used as controls.
      Other groups of intact rats were implanted with HAL or sham-implanted for 9
      months and then were implanted with PRL-producing MMQ cells for 6 weeks to
      further increase circulating PRL levels. TIDA neuronal activity was measured in
      terms of tyrosine hydroxylase (TH) activity in the stalk-median eminence and was
      correlated with changes in serum PRL levels. After 6 months of treatment, TH
      activity in HAL-treated rats was 130% higher than that in the control rats. After
      9 months of treatment, TH activity in HAL-treated rats was 81% higher than that
      in control rats. This increase was significantly less than the increase that
      occurred after 6 months of treatment. Nine months of HAL-induced
      hyperprolactinemia followed by implantation of PRL-producing MMQ cells, which
      resulted in very high levels of PRL, did not increase TH activity in the stalk
      median eminence. These results demonstrate that hyperprolactinemia over a
      prolonged period reduces the responsiveness of TIDA neurons, and these effects
      vary depending on the duration and intensity of hyperprolactinemia.

PMID- 9521093
TI  - Influences of age and reproductive status on ovarian ovulatory responsiveness to
      gonadotropin stimulation.
AB  - Reproductive aging in the female rat is associated with the gradual loss of
      regular ovulatory function, decreased fertility, and smaller litter sizes. In the
      present study, we assessed ovarian ovulatory responsiveness to exogenous
      gonadotropin stimulation in young and middle-aged cyclic females and in middle
      aged acyclic persistent-estrous (PE) rats. The ovulatory response to human
      chorionic gonadotropin (hCG) was dose-dependent in both young and middle-aged
      cyclic rats, with the percentages of rats ovulating and the numbers of ova shed
      per rat increasing with the dose of hCG administered. At the highest dose tested
      (10 mIU hCG/g bw), the range in ovulation rates among middle-aged cyclic rats (0
      18 ova shed/rat) was greater than that in young animals (12-18 ova/rat). However,
      there were no statistically significant differences in either the percentages of
      females ovulating or in the mean ovulation rates between young and middle-aged
      cyclic groups. In contrast to the normal ovulatory responses observed in most
      middle-aged cyclic animals, response to hCG was markedly impaired in PE females
      of the same age. Middle-aged PE rats consistently failed to ovulate in response
      to a dose of hCG (10 mIU/g bw), which elicited high ovulation rates in young
      rats. At an even higher dose (20 mIU/g bw), only minimal ovulatory responses were
      observed (1.8 +/- 0.8 ova/rat; 80% of rats ovulating). Thus, most middle-aged
      regularly cyclic females maintain a similar ovulatory responsiveness to hCG as
      young rats, suggesting that decreased ovulation rates during aging may be related
      to attenuated preovulatory LH surges. However, impaired ovulatory responses were
      observed in middle-aged PE females, indicating altered ovarian function in
      acyclic animals, which may contribute to their anovulatory state.

PMID- 9521096
TI  - Aerosolized hyaluronic acid decreases alveolar injury induced by human neutrophil
      elastase.
AB  - This laboratory has previously shown that an intratracheally instilled solution
      of hyaluronic acid (HA) protects the lung from elastase-induced airspace
      enlargement. In those studies, fluorescein-labeled HA was found to bind
      preferentially to lung elastic fibers, suggesting a mechanism for the protective
      effect. The current investigation extends these findings by examining the
      capacity of an aerosol preparation of HA to similarly inhibit elastase-induced
      lung injury. Syrian hamsters were exposed to aerosolized bovine tracheal HA (0.1%
      solution in water) for either 25 or 50 min, then immediately instilled
      intratracheally with 80 units of human neutrophil elastase. One week later the
      lungs were examined for airspace enlargement, using the mean linear intercept
      method. Animals exposed to HA for 50 min showed a significant decrease in
      airspace enlargement compared to controls exposed to aerosolized water alone
      (68.2 microm vs 85.9 microm; P < 0.05). The 25-min exposure to the HA aerosol
      also reduced the mean linear intercept compared to controls (73.7 microm vs 85.9
      microm), but this decrease was not statistically significant. With regard to
      possible inflammatory effects of HA, there was no difference in the percentage of
      lavaged neutrophils between HA-treated and control lungs at 24 hr (1.4% vs 1.8%,
      respectively). As with earlier experiments using intratracheally instilled HA,
      aerosolized fluorescein-labeled HA was found to bind to lung elastic fibers.
      These results suggest that aerosolized HA may prevent elastase-mediated injury in
      pulmonary emphysema.

PMID- 9521095
TI  - Alleles of the cholesterol 7 alpha-hydroxylase (CYP7) gene in pigs selected for
      high or low plasma total cholesterol.
AB  - Crossbred pigs were selected for high (HTC) or low (LTC) plasma total cholesterol
      (TC). Pigs from the seventh (n = 51) and eighth (n = 92) generations were used to
      determine restriction fragment length polymorphisms (RFLP). Using TaqI
      restriction enzyme digestion, the frequencies of two alleles (2.8- or 5.0-kb
      fragments) of the cholesterol 7 alpha-hydroxylase (CYP7) gene were determined in
      the two populations as a potential indicator of TC concentration at 8 weeks of
      age. Only the 2.8-kb fragment allele was present in the 26 HTC pigs tested in
      Generation 7. In the LTC pigs both the 2.8- and 5.0-kb alleles were present in 12
      pigs, and only the 5.0-kb allele was present in 13 pigs. The allele frequencies
      of the 2.8 and 5.0 fragments, respectively, were .26 and .74 in LTC pigs and 1.00
      and 0 in HTC pigs. There was an association (P < .001) between the 5.0- and 2.8
      kb CYP7 alleles, respectively, and low and high TC concentrations. In Generation
      8, all HTC pigs were homozygous for the 2.8-kb allele. The 5.0 kb allele was
      present in all LTC pigs tested and was homozygous in 57% of LTC pigs. Mean plasma
      TC was 105.0 mg/dl in 30 pigs homozygous for the 2.8-kb allele in Generation 8;
      means for LTC pigs were 53.5 and 60.4 mg/dl in 35 pigs homozygous for the 5.0-kb
      allele and in 27 heterozygous pigs, respectively. High TC was associated with the
      presence of the 2.8-kb allele, and low TC was associated with the presence of the
      5.0-kb allele in both Generations 7 and 8. We conclude that TaqI RFLP analysis of
      the CYP7 gene is a reliable indicator for TC in these swine.

PMID- 9521097
TI  - Differential modulation of human (Caco-2) colon cancer cell line phenotype by
      short chain fatty acids.
AB  - Fermentation of dietary fiber within the colonic lumen yields short chain fatty
      acids (SCFA) such as butyrate, which may modulate colonic mucosal biology and
      inhibit the development of a malignant phenotype. However, different fibers yield
      varying proportions of various SCFA. We studied the effects of the three most
      common SCFA, acetate, butyrate, and propionate, on the proliferation, adhesion,
      and motility of the human intestinal Caco-2 cell line, as well as the effects of
      these SCFA on alkaline phosphatase and dipeptidyl dipeptidase specific activity
      (common laboratory markers of differentiation). In addition, we examined the
      modulation of c-myc protein and the tyrosine phosphorylation of cellular proteins
      by these SCFA in order to determine whether the variations in the potency of
      these three SCFA for phenotypic change extended to variations in effects on
      intracellular signaling and protooncogene expression. All three SCFA tended to
      slow proliferation, promote brush border enzyme activity, and inhibit both
      adhesion to and motility across a type I collagen matrix substrate. However, we
      observed substantial differences in the potency of these three SCFA with regard
      to these effects. In particular, butyrate was uniformly more potent than an
      equimolar concentration of acetate whereas equimolar propionate achieved
      comparable effects with regard to proliferation and brush border enzyme activity
      but was intermediate between butyrate and acetate with regard to modulation of
      cell-matrix interactions. Similarly, the SCFA downregulated c-myc protein levels
      and modulated the phosphorylation of several intracellular tyrosine
      phosphoproteins, but the effects of the three SCFA varied substantially for these
      parameters. These results suggest that the common short chain fatty acids are not
      equipotent in their effects on human Caco-2 colon cancer cell biology. Such
      differences in potency could contribute to the observed differences in effects of
      different dietary fibers in vivo.

PMID- 9521098
TI  - Domain assignment for protein structures using a consensus approach:
      characterization and analysis.
AB  - A consensus approach for the assignment of structural domains in proteins is
      presented. The approach combines a number of previously published algorithms, and
      takes advantage of the elevated accuracy obtained when assignments from the
      individual algorithms are in agreement. The consensus approach is tested on a
      data set of 55 protein chains, for which domain assignments from four automated
      methods were known, and for which crystallographers assignments had been reported
      in the literature. Accuracy was found to increase in this test from 72% using
      individual algorithms to 100% when all four methods were in agreement. However a
      consensus prediction using all four methods was only possible for 52% of the
      dataset. The consensus approach [using three publicly available domain assignment
      algorithms (PUU, DETECTIVE, DOMAK)] was then used to make domain assignments for
      a data set of 787 protein chains from the Protein Data Bank. Analysis of the
      assignments showed 55.7% of assignments could be made automatically, and of
      these, 13.5% were multi-domain proteins. Of the remaining 44.3% that could not be
      assigned by the consensus procedure 90.4% had their domain boundaries assigned
      correctly by at least one of the algorithms. Once identified, these domains were
      analyzed for trends in their size and secondary structure class. In addition, the
      discontinuity of each domain along the protein chain was considered.

PMID- 9521100
TI  - Alignment algorithm for homology modeling and threading.
AB  - A DNA/protein sequence comparison is a popular computational tool for molecular
      biologists. Finding a good alignment implies an evolutionary and/or functional
      relationship between proteins or genomic loci. Sequential similarity between two
      proteins indicates their structural resemblance, providing a practical approach
      for structural modeling, when structure of one of these proteins is known. The
      first step in the homology modeling is a construction of an accurate sequence
      alignment. The commonly used alignment algorithms do not provide an adequate
      treatment of the structurally mismatched residues in locally dissimilar regions.
      We propose a simple modification of the existing alignment algorithm which treats
      these regions properly and demonstrate how this modification improves sequence
      alignments in real proteins.

PMID- 9521099
TI  - Hirunorms are true hirudin mimetics. The crystal structure of human alpha
      thrombin-hirunorm V complex.
AB  - A novel class of synthetic, multisite-directed thrombin inhibitors, known as
      hirunorms, has been described recently. These compounds were designed to mimic
      the binding mode of hirudin, and they have been proven to be very strong and
      selective thrombin inhibitors. Here we report the crystal structure of the
      complex formed by human alpha-thrombin and hirunorm V, a 26-residue polypeptide
      containing non-natural amino acids, determined at 2.1 A resolution and refined to
      an R-factor of 0.176. The structure reveals that the inhibitor binding mode is
      distinctive of a true hirudin mimetic, and it highlights the molecular basis of
      the high inhibitory potency (Ki is in the picomolar range) and the strong
      selectivity of hirunorm V. Hirunorm V interacts through the N-terminal
      tetrapeptide with the thrombin active site in a nonsubstrate mode; at the same
      time, this inhibitor specifically binds through the C-terminal segment to the
      fibrinogen recognition exosite. The backbone of the N-terminal tetrapeptide Chg1"
      Val2"-2-Nal3"-Thr4" (Chg, cyclohexyl-glycine; 2-Nal, beta-(2-naphthyl)-alanine)
      forms a short beta-strand parallel to thrombin main-chain residues Ser214-Gly219.
      The Chg1" side chain fills the S2 subsite, Val2" is located at the entrance of
      S1, whereas 2-Nal3" side chain occupies the aryl-binding site. Such backbone
      orientation is very close to that observed for the N-terminal residues of
      hirudin, and it is similar to that of the synthetic retro-binding peptide BMS
      183507, but it is opposite to the proposed binding mode of fibrinogen and of
      small synthetic substrates. Hirunorm V C-terminal segment binds to the fibrinogen
      recognition exosite, similarly to what observed for hirudin C-termninal tail and
      related compounds. The linker polypeptide segment connecting hirunorm V N-and C
      terminal regions is not observable in the electron density maps. The
      crystallographic analysis proves the correctness of the design and it provides a
      compelling proof on the interaction mechanism for this novel class of high
      potency multisite-directed synthetic thrombin inhibitors.

PMID- 9521101
TI  - Determination and analysis of antigenic epitopes of prostate specific antigen
      (PSA) and human glandular kallikrein 2 (hK2) using synthetic peptides and
      computer modeling.
AB  - Prostate specific antigen (PSA) and human glandular kallikrein 2 (hK2), produced
      essentially by the prostate gland, are 237-amino acid monomeric proteins, with
      79% identity in primary structure. Twenty-five anti-PSA monoclonal antibodies
      (Mabs) were studied for binding to a large array of synthetic linear peptides
      selected from computer models of PSA and hK2, as well as to biotinylated peptides
      covering the entire PSA sequence. Sixteen of the Mabs were bound to linear
      peptides forming four independent binding regions (I-IV). Binding region I was
      localized to amino acid residues 1-13 (identical sequence for PSA and hK2), II (a
      and b) was localized to residues 53-64, III (a and b) was localized to residues
      80-91 (= kallikrein loop), and IV was localized to residues 151-164. Mabs binding
      to regions I and IIa were reactive with free PSA, PSA-ACT complex, and with hK2;
      Mabs binding to regions IIb, IIIa, and IV were reactive with free PSA and PSA-ACT
      complex, but unreactive with hK2; Mabs binding to region IIIb detected free PSA
      only. All Mabs tested (n = 7) specific for free PSA reacted with kallikrein loop
      (binding region IIIb). The presence of Mabs interacting with binding region I did
      not inhibit the catalytic activity of PSA, whereas Mabs interacting with other
      binding regions inhibited the catalysis. Theoretical model structures of PSA,
      hK2, and the PSA-ACT complex were combined with the presented data to suggest an
      overall orientation of PSA with regard to ACT.

PMID- 9521102
TI  - An interaction-based analysis of calcium-induced conformational changes in Ca2+
      sensor proteins.
AB  - Calcium sensor proteins translate transient increases in intracellular calcium
      levels into metabolic or mechanical responses, by undergoing dramatic
      conformational changes upon Ca2+ binding. A detailed analysis of the calcium
      binding-induced conformational changes in the representative calcium sensors
      calmodulin (CaM) and troponin C was performed to obtain insights into the
      underlying molecular basis for their response to the binding of calcium. Distance
      difference matrices, analysis of interresidue contacts, comparisons of
      interhelical angles, and inspection of structures using molecular graphics were
      used to make unbiased comparisons of the various structures. The calcium-induced
      conformational changes in these proteins are dominated by reorganization of the
      packing of the four helices within each domain. Comparison of the closed and open
      conformations confirms that calcium binding causes opening within each of the EF
      hands. A secondary analysis of the conformation of the C-terminal domain of CaM
      (CaM-C) clearly shows that CaM-C occupies a closed conformation in the absence of
      calcium that is distinct from the semi-open conformation observed in the C
      terminal EF-hand domains of myosin light chains. These studies provide insight
      into the structural basis for these changes and into the differential response to
      calcium binding of various members of the EF-hand calcium-binding protein family.
      Factors contributing to the stability of the Ca2+-loaded open conformation are
      discussed, including a new hypothesis that critical hydrophobic interactions
      stabilize the open conformation in Ca2+ sensors, but are absent in "non-sensor"
      proteins that remain closed upon Ca2+ binding. A role for methionine residues in
      stabilizing the open conformation is also proposed.

PMID- 9521103
TI  - Structures of adamalysin II with peptidic inhibitors. Implications for the design
      of tumor necrosis factor alpha convertase inhibitors.
AB  - Crotalus adamanteus snake venom adamalysin II is the structural prototype of the
      adamalysin or ADAM family comprising proteolytic domains of snake venom
      metalloproteinases, multimodular mammalian reproductive tract proteins, and tumor
      necrosis factor alpha convertase, TACE, involved in the release of the
      inflammatory cytokine, TNFalpha. The structure of adamalysin II in noncovalent
      complex with two small-molecule right-hand side peptidomimetic inhibitors (Pol
      647 and Pol 656) has been solved using X-ray diffraction data up to 2.6 and 2.8 A
      resolution. The inhibitors bind to the S'-side of the proteinase, inserting
      between two protein segments, establishing a mixed parallel-antiparallel three
      stranded beta-sheet and coordinate the central zinc ion in a bidentate manner via
      their two C-terminal oxygen atoms. The proteinase-inhibitor complexes are
      described in detail and are compared with other known structures. An adamalysin
      based model of the active site of TACE reveals that these small molecules would
      probably fit into the active site cleft of this latter metalloproteinase,
      providing a starting model for the rational design of TACE inhibitors.

PMID- 9521105
TI  - Active-site mobility in human immunodeficiency virus, type 1, protease as
      demonstrated by crystal structure of A28S mutant.
AB  - The mutation Ala28 to serine in human immunodeficiency virus, type 1, (HIV-1)
      protease introduces putative hydrogen bonds to each active-site carboxyl group.
      These hydrogen bonds are ubiquitous in pepsin-like eukaryotic aspartic proteases.
      In order to understand the significance of this difference between HIV-1 protease
      and homologous, eukaryotic aspartic proteases, we solved the three-dimensional
      structure of A28S mutant HIV-1 protease in complex with a peptidic inhibitor U
      89360E. The structure has been determined to 2.0 A resolution with an R factor of
      0.194. Comparison of the mutant enzyme structure with that of the wild-type HIV-1
      protease bound to the same inhibitor (Hong L, Treharne A, Hartsuck JA, Foundling
      S, Tang J, 1996, Biochemistry 35:10627-10633) revealed double occupancy for the
      Ser28 hydroxyl group, which forms a hydrogen bond either to one of the oxygen
      atoms of the active-site carboxyl or to the carbonyl oxygen of Asp30. We also
      observed marked changes in orientation of the Asp25 catalytic carboxyl groups,
      presumably caused by the new hydrogen bonds. These observations suggest that
      catalytic aspartyl groups of HIV-1 protease have significant conformational
      flexibility unseen in eukaryotic aspartic proteases. This difference may provide
      an explanation for some unique catalytic properties of HIV-1 protease.

PMID- 9521104
TI  - Substrate binding and conformational changes of Clostridium glutamicum
      diaminopimelate dehydrogenase revealed by hydrogen/deuterium exchange and
      electrospray mass spectrometry.
AB  - C. glutamicum meso-diaminopimelate dehydrogenase is an enzyme of the L-lysine
      biosynthetic pathway in bacteria. The binding of NADPH and diaminopimelate to the
      recombinant, overexpressed enzyme has been analyzed using hydrogen/deuterium
      exchange and electrospray ionization/mass spectrometry. NADPH binding reduces the
      extent of deuterium exchange, as does the binding of diaminopimelate. Pepsin
      digestion of the deuterated enzyme and enzyme-substrate complexes coupled with
      liquid chromatography/mass spectrometry have allowed the identification of eight
      peptides whose deuterium exchange slows considerably upon the binding of the
      substrates. These peptides represent regions known or thought to bind NADPH and
      diaminopimelate. One of these peptides is located at the interdomain hinge region
      and is proposed to be exchangeable in the "open," catalytically inactive,
      conformation but nonexchangeable in the "closed," catalytically active
      conformation formed after NADPH and diaminopimelate binding and domain closure.
      Furthermore, the dimerization region has been localized by this method, and this
      study provides an example of detecting protein-protein interface regions using
      hydrogen/deuterium exchange and electrospray ionization.

PMID- 9521106
TI  - Apparent local stability of the secondary structure of Azotobacter vinelandii
      holoflavodoxin II as probed by hydrogen exchange: implications for redox
      potential regulation and flavodoxin folding.
AB  - As a first step to determine the folding pathway of a protein with an alpha/beta
      doubly wound topology, the 1H, 13C, and 15N backbone chemical shifts of
      Azotobacter vinelandii holoflavodoxin II (179 residues) have been determined
      using multidimensional NMR spectroscopy. Its secondary structure is shown to
      contain a five-stranded parallel beta-sheet (beta2-beta1-beta3-beta4-beta5) and
      five alpha-helices. Exchange rates for the individual amide protons of
      holoflavodoxin were determined using the hydrogen exchange method. The amide
      protons of 65 residues distributed throughout the structure of holoflavodoxin
      exchange slowly at pH* 6.2 [kex < 10(-5) s(-1)] and can be used as probes in
      future folding studies. Measured exchange rates relate to apparent local free
      energies for transient opening. We propose that the amide protons in the core of
      holoflavodoxin only exchange by global unfolding of the apo state of the protein.
      The results obtained are discussed with respect to their implications for
      flavodoxin folding and for modulation of the flavin redox potential by the
      apoprotein. We do not find any evidence that A. vinelandii holoflavodoxin II is
      divided into two subdomains based on its amide proton exchange rates, as opposed
      to what is found for the structurally but not sequentially homologous alpha/beta
      doubly wound protein Che Y.

PMID- 9521107
TI  - Identification of a specific tyrosine residue in Bryodin 1 distinct from the
      active site but required for full catalytic and cytotoxic activity.
AB  - Bryodin 1 (BD1) is a type I ribosome-inactivating protein (RIP) with low inherent
      animal toxicity. It has been cloned recently and the recombinant protein (rBD1)
      has been produced and crystallized. To gain insight into the relationship of rBD1
      structure and function, we investigated the role of sequences in a region
      (residues 128-156) that exhibits homology with membrane interactive sequences and
      is not part of the enzymatically defined active site. Progressive deletions
      representing alpha-helical tums within these residues were generated; mutant rBD1
      proteins were expressed in Escherichia coli and demonstrated increasing losses of
      enzymatic activity. Point mutations were also generated within this region to
      replace Y140, Y141, and Y142 with either alanine or lysine. Mutants at position
      140 or 142 retained full enzymatic activity, whereas A141 and K141 mutants were
      >19-fold less potent. In cytotoxicity assays, the rBD1 point mutants at Y141 were
      >80-fold less potent than either rBD1 or mutants at residues 140 or 142. However,
      when introduced into the anti-CD40 single-chain immunotoxin rBD1-G28-5 sFv, the
      A140 and A141 point mutations led to decreased cytotoxicity toward CD40 positive
      cell lines. These data indicate that Y141 plays an important role in the
      enzymatic activity of BD1 and that Y140, although not essential for catalytic
      activity, is required for full BD1 function. Because residues 140 and 141 are
      distinct from residues implicit in the active site, they may be involved in
      ribosomal and/or membrane interactions or in intracellular trafficking of the
      toxin and immunotoxin.

PMID- 9521108
TI  - Exploring sequence constraints on an interhelical turn using in vivo selection
      for catalytic activity.
AB  - The role of interhelical turns in determining protein structure has been
      investigated previously in relatively simple four-helix-bundle proteins using
      combinatorial mutagenesis coupled with screening for functional variants. To
      assess the tolerance to sequence substitution of a short, interhelical turn in a
      larger, more complicated protein, we have exploited a more sensitive in vivo
      selection for catalytic activity. Randomization of three solvent-exposed turn
      residues in Escherichia coli chorismate mutase (Ala65, His66, and His67),
      followed by selection, indicated that >63% of tripeptides, including some with
      significantly altered backbone conformations, can functionally replace the native
      sequence. The increased sensitivity of the catalytic assay allowed optimal
      sequences to be distinguished from less appropriate ones, revealing a
      statistically significant preference for hydrophilic residues in solvent-exposed
      positions. It also enabled investigation of the extent to which either secondary
      structure or tertiary interactions influence substitution patterns. Randomization
      of an alpha-helical residue (Lys64), together with the adjacent solvent-exposed
      tripeptide, Ala65-His66-His67, showed that the secondary structure at position 64
      does not limit the range of side chains allowed at this site. In contrast,
      randomization of a buried turn residue (Leu68), together with the same
      tripeptide, revealed an extremely strict requirement for hydrophobic aliphatic
      amino acids at this position. The strong constraint imposed by the tertiary
      interaction, in contrast to the weak influence of secondary structure, has
      important implications for protein design.

PMID- 9521109
TI  - Interhelical contacts are required for the helix bundle fold of apolipophorin III
      and its ability to interact with lipoproteins.
AB  - Apolipophorin-III (apoLp-III) from the insect, Manduca sexta, is a 166-residue
      exchangeable apolipoprotein that plays a critical role in the dynamics of plasma
      lipoprotein interconversions. Our previous work indicated that a 36-residue C
      terminal peptide fragment, generated by cyanogen bromide digestion of apoLp-III,
      was unable to bind to lipid surfaces (Narayanaswami V, Kay CM, Oikawa K, Ryan RO,
      1994, Biochemistry 33:13312-13320), and showed no secondary structure in aqueous
      solution. In this paper, we have performed structural studies of this peptide
      (E131-Q166) complexed with SDS detergent micelles, or in the presence of the
      helix-inducing solvent trifluoroethanol (TFE), by two-dimensional 1H NMR
      spectroscopy. The peptide adopts an alpha-helical structure in the presence of
      both SDS and 50% TFE. The lipid-bound structure of the peptide, generated from
      the NMR NOE data, showed an elongated, slightly curved alpha-helix. Despite its
      high alpha-helix forming propensity, the peptide requires alpha helix-promoting
      environment to adopt an alpha-helical structure. This indicates the importance of
      the surrounding chemical environment and implies that, in the absence of lipid,
      tertiary contacts in the folded protein play a role in maintaining its structural
      integrity. Furthermore, the data suggest that the amphipathic helix bundle
      organization serves as a prerequisite structural motif for the reversible
      lipoprotein-binding activity of M. sexta apoLp-III.

PMID- 9521110
TI  - Solid-state NMR studies of the membrane-bound closed state of the colicin E1
      channel domain in lipid bilayers.
AB  - The colicin E1 channel polypeptide was shown to be organized anisotropically in
      membranes by solid-state NMR analysis of samples of uniformly 15N-labeled protein
      in oriented planar phospholipid bilayers. The 190 residue C-terminal colicin E1
      channel domain is the largest polypeptide to have been characterized by 15N solid
      state NMR spectroscopy in oriented membrane bilayers. The 15N-NMR spectra of the
      colicin E1 show that: (1) the structure and dynamics are independent of anionic
      lipid content in both oriented and unoriented samples; (2) assuming the secondary
      structure of the polypeptide is helical, there are both trans-membrane and in
      plane helical segments; (3) trans-membrane helices account for approximately 20
      25% of the channel polypeptide, which is equivalent to 38-48 residues of the 190
      residue polypeptide. The results of the two-dimensional PISEMA spectrum are
      interpreted in terms of a single trans-membrane helical hairpin inserted into the
      bilayer from each channel molecule. These data are also consistent with this
      helical hairpin being derived from the 38-residue hydrophobic segment near the C
      terminus of the colicin E1 channel polypeptide.

PMID- 9521111
TI  - Reactivities of the S2 and S3 subsite residues of thrombin with the native and
      heparin-induced conformers of antithrombin.
AB  - A pentasaccharide (PS) fragment of heparin capable of activating antithrombin
      (AT) markedly accelerates the inhibition of factor Xa by AT, but has
      insignificant effect on inhibition of thrombin. For inhibition of thrombin, the
      bridging function of a longer polysaccharide chain is required to accelerate the
      reaction. To study the basis for the similar reactivity of thrombin with the
      native or heparin-activated conformers of AT, several residues surrounding the
      active site pocket of thrombin were targeted for mutagenesis study. Leu99 and
      Glu192, the variant residues influencing the S2 and S3 subsite specificity of
      thrombin were replaced with Tyr and Gln. The Tyr60a, Pro60b, Pro60c, and Trp60d
      residues forming part of the S2 specificity pocket were deleted from the B
      insertion loop of the wild-type and Leu99/Glu192 --> Tyr/Gln thrombins. Kinetic
      studies indicated that the reactivities of all mutants with AT were moderately or
      severely impaired. Although heparin largely corrected the defect in reactivities,
      it also markedly elevated the stoichiometries of inhibition with the mutants.
      Interestingly, PS also accelerated AT inhibition of the mutants 5-68-fold,
      suggesting that the mutants are able to discriminate between the native and
      activated conformers of AT. Based on these results and the recent crystal
      structure determination of AT in complex with PS, a model for thrombin-AT
      interaction is proposed in which the S2 and S3 subsite residues of thrombin are
      critical for recognition of the P2 and P3 residues of AT in the native
      conformation. In the activated conformation, other residues are made accessible
      for interaction with the protease, and the similar reactivity of thrombin with
      the native and heparin-activated conformers of AT may be coincidental. The
      results further suggest that the S2 and S3 subsite residues are crucial in
      controlling the partitioning of the thrombin-AT intermediate into the alternative
      inhibitory or substrate pathways of the reaction.

PMID- 9521112
TI  - A folding pathway for betapep-4 peptide 33mer: from unfolded monomers and beta
      sheet sandwich dimers to well-structured tetramers.
AB  - It was recently reported that a de novo designed peptide 33mer, betapep-4, can
      form well-structured beta-sheet sandwich tetramers (Ilyina E, Roongta V, Mayo KH,
      1997b, Biochemistry 36:5245-5250). For insight into the pathway of betapep-4
      folding, the present study investigates the concentration dependence of betapep-4
      self-association by using 1H-NMR pulsed-field gradient (PFG)-NMR diffusion
      measurements, and circular dichroism. Downfield chemically shifted alphaH
      resonances, found to arise only from the well-structured betapep-4 tetramer
      state, yield the fraction of tetramer within the oligomer equilibrium
      distribution. PFG-NMR-derived diffusion coefficients, D, provide a means for
      deriving the contribution of monomer and other oligomer states to this
      distribution. These data indicate that tetramer is the highest oligomer state
      formed, and that inclusion of monomer and dimer states in the oligomer
      distribution is sufficient to explain the concentration dependence of D values
      for betapep-4. Equilibrium constants calculated from these distributions [2.5 x
      10(5) M(-1) for M-D and 1.2 x 10(4) M(-1) for D-T at 313 K] decrease only
      slightly, if at all, with decreasing temperature indicating a hydrophobically
      mediated, entropy-driven association/folding process. Conformational analyses
      using NMR and CD provide a picture where "random coil" monomers associate to form
      molten globule-like beta-sheet sandwich dimers that further associate and fold as
      well-structured tetramers. Betapep-4 folding is thermodynamically linked to self
      association. As with folding of single-chain polypeptides, the final folding step
      to well-structured tetramer betapep-4 is rate limiting.

PMID- 9521113
TI  - Thioredoxin reductase from Escherichia coli: evidence of restriction to a single
      conformation upon formation of a crosslink between engineered cysteines.
AB  - Thioredoxin reductase is a flavoprotein which catalyzes the reduction of the
      small protein thioredoxin by NADPH. It contains a redox active disulfide and an
      FAD in each subunit of its dimeric structure. Each subunit is further divided
      into two domains, the FAD and the pyridine nucleotide binding domains. The
      orientation of the two domains determined from the crystal structure and the flow
      of electrons determined from mechanistic studies suggest that thioredoxin
      reductase requires a large conformational change to carry out catalysis (Williams
      CH Jr, 1995, FASEB J 9:1267-1276). The constituent amino acids of an ion pair,
      E48/R130, between the FAD and pyridine nucleotide binding domains, were
      mutagenized to cysteines to form E48C,R130C (CC mutant). Formation of a stable
      bridge between these cysteines was expected to restrict the enzyme largely in the
      conformation observed in the crystal structure. Crosslinking with the
      bifunctional reagent N,N,1,2 phenylenedimaleimide, spanning 4-9 A, resulted in a
      >95 % decrease in thioredoxin reductase and transhydrogenase activity. SDS-PAGE
      confirmed that the crosslink in the CC-mutant was intramolecular. Dithionite
      titration showed an uptake of electrons as in wild-type enzyme, but anaerobic
      reduction of the flavin with NADPH was found to be impaired. This indicates that
      the crosslinked enzyme is in the conformation where the flavin and the active
      site disulfide are in close proximity but the flavin and pyridinium rings are too
      far apart for effective electron transfer. The evidence is consistent with the
      hypothesis that thioredoxin reductase requires a conformational change to
      complete catalysis.

PMID- 9521114
TI  - Three solutions of the protein solubility problem.
AB  - Three simple equations are presented, which describe the variation of protein
      solubility (S) with changes in salt concentration, in terms of either the salt
      molality (M), the salt activity (ax), or the water activity (aw). Each equation
      yields, essentially independent, estimates of the numbers of salt ions (delta vx)
      and water molecules (delta vw) involved in the dissolution of a mol of the
      protein. The equations can be used to elucidate the physical significance of the
      parameters in other empirical equations for protein solubility.

PMID- 9521115
TI  - Trifluoroethanol effects on helix propensity and electrostatic interactions in
      the helical peptide from ribonuclease T1.
AB  - Trifluoroethanol (TFE) is often used to increase the helicity of peptides to make
      them usable as models of helices in proteins. We have measured helix propensities
      for all 20 amino acids in water and two concentrations of trifluoroethanol, 15
      and 40% (v/v) using, as a model system, a peptide derived from the sequence of
      the alpha-helix of ribonuclease T1. There are three main conclusions from our
      studies. (1) TFE alters electrostatic interactions in the ribonuclease T1 helical
      peptide such that the dependence of the helical content on pH is lost in 40% TFE.
      (2) Helix propensities measured in 15% TFE correlate well with propensities
      measured in water, however, the correlation with propensities measured in 40% TFE
      is significantly worse. (3) Propensities measured in alanine-based peptides and
      the ribonuclease T1 peptide in TFE show very poor agreement, revealing that TFE
      greatly increases the effect of sequence context.

PMID- 9521116
TI  - 15N backbone dynamics of the S-peptide from ribonuclease A in its free and S
      protein bound forms: toward a site-specific analysis of entropy changes upon
      folding.
AB  - Backbone 15N relaxation parameters (R1, R2, 1H-15N NOE) have been measured for a
      22-residue recombinant variant of the S-peptide in its free and S-protein bound
      forms. NMR relaxation data were analyzed using the "model-free" approach (Lipari
      & Szabo, 1982). Order parameters obtained from "model-free" simulations were used
      to calculate 1H-15N bond vector entropies using a recently described method (Yang
      & Kay, 1996), in which the form of the probability density function for bond
      vector fluctuations is derived from a diffusion-in-a-cone motional model. The
      average change in 1H-15N bond vector entropies for residues T3-S15, which become
      ordered upon binding of the S-peptide to the S-protein, is -12.6+/-1.4
      J/mol.residue.K. 15N relaxation data suggest a gradient of decreasing entropy
      values moving from the termini toward the center of the free peptide. The
      difference between the entropies of the terminal and central residues is about 
      12 J/mol residue K, a value comparable to that of the average entropy change per
      residue upon complex formation. Similar entropy gradients are evident in NMR
      relaxation studies of other denatured proteins. Taken together, these
      observations suggest denatured proteins may contain entropic contributions from
      non-local interactions. Consequently, calculations that model the entropy of a
      residue in a denatured protein as that of a residue in a di- or tri-peptide,
      might over-estimate the magnitude of entropy changes upon folding.

PMID- 9521117
TI  - Crystal structures of CheY from Thermotoga maritima do not support conventional
      explanations for the structural basis of enhanced thermostability.
AB  - The crystal structure of CheY protein from Thermotoga maritima has been
      determined in four crystal forms with and without Mg++ bound, at up to 1.9 A
      resolution. Structural comparisons with CheY from Escherichia coli shows
      substantial similarity in their folds, with some concerted changes propagating
      away from the active site that suggest how phosphorylated CheY, a signal
      transduction protein in bacterial chemotaxis, is recognized by its targets. A
      highly conserved segment of the protein (the "y-turn loop," residues 55-61),
      previously suggested to be a rigid recognition determinant, is for the first time
      seen in two alternative conformations in the different crystal structures.
      Although CheY from Thermotoga has much higher thermal stability than its
      mesophilic counterparts, comparison of structural features previously proposed to
      enhance thermostability such as hydrogen bonds, ion pairs, compactness, and
      hydrophobic surface burial would not suggest it to be so.

PMID- 9521119
TI  - Expansion of the genetic code: site-directed p-fluoro-phenylalanine incorporation
      in Escherichia coli.
AB  - Site-directed incorporation of the amino acid analogue p-fluoro-phenylalanine (p
      F-Phe) was achieved in Escherichia coli. A yeast suppressor
      tRNA(Phe)amber/phenylalanyl-tRNA synthetase pair was expressed in an analogue
      resistant E. coli strain to direct analogue incorporation at a programmed amber
      stop codon in the DHFR marker protein. The programmed position was translated to
      64-75% as p-F-Phe and the remainder as phenylalanine and lysine. Depending on the
      expression conditions, the p-F-Phe incorporation was 11-21-fold higher at the
      programmed position than the background incorporation at phenylalanine codons,
      showing high specificity of analogue incorporation. Protein expression yields of
      8-12 mg/L of culture, corresponding to about two thirds of the expression level
      of the wild-type DHFR protein, are sufficient to provide fluorinated proteins
      suitable for 19F-NMR spectroscopy and other sample-intensive methods. The use of
      a nonessential "21st" tRNA/synthetase pair will permit incorporation of a wide
      range of analogues, once the synthetase specificity has been modified
      accordingly.

PMID- 9521118
TI  - Engineering protein for X-ray crystallography: the murine Major
      Histocompatibility Complex class II molecule I-Ad.
AB  - Class II Major Histocompatibility (MHC) molecules are cell surface heterodimeric
      glycoproteins that play a central role in the immune response by presenting
      peptide antigens for surveillance by T cells. Due to the inherent instability of
      the class II MHC heterodimer, and its dependence on bound peptide for proper
      assembly, the production of electrophoretically pure samples of class II MHC
      proteins in complex with specific peptides has been problematic. A soluble form
      of the murine class II MHC molecule, I-Ad, with a leucine zipper tail added to
      each chain to enhance dimer assembly and secretion, has been produced in
      Drosophila melanogaster SC2 cells. To facilitate peptide loading, a high affinity
      ovalbumin peptide was covalently engineered to be attached by a six-residue
      linker to the amino terminus of the I-Adbeta chain. This modified I-Ad molecule
      was purified using preparative IEF and one fraction, after removal of the leucine
      zipper tails, produced crystals suitable for X-ray crystallographic analysis. The
      protein engineering and purification methods described here should be of general
      value for the expression of I-A and other class II MHC-peptide complexes.

PMID- 9521120
TI  - Formation and movement of Fe(III) in horse spleen, H- and L-recombinant
      ferritins. A fluorescence study.
AB  - Iron oxidation and incorporation into apoferritins of different subunit
      composition, namely the recombinant H and L homopolymers and the natural horse
      spleen heteropolymer (10-15% H), have been followed by steady-state and time
      resolved fluorescence. After aerobic addition of 100 Fe(II) atoms/polymer,
      markedly different kinetic profiles are observed. In the rL-homopolymer a slow
      monotonic fluorescence quenching is observed which reflects binding, slow
      oxidation at the threefold apoferritin channels, and diffusion into the protein
      cavity. In the rH-homopolymer a fast fluorescence quenching is followed by a
      partial, slow recovery. The two processes have been attributed to Fe(II) binding
      and oxidation at the ferroxidase centers and to Fe(III) released into the cavity,
      respectively. The fluorescence kinetics of horse spleen apoferritin is dominated
      by the H chain contribution and resembles that of the H homopolymer. It brings
      out clearly that the rate of the overall process is limited by the rate at which
      Fe(III) leaves the ferroxidase centers of the H chains where binding of incoming
      Fe(II) and its oxidation take place. The data obtained upon stepwise addition of
      iron and the results of optical absorption measurements confirm this picture. The
      correspondence between steady-state and time-resolved data is remarkably good;
      this is manifest when the latter are used to calculate the change in fluorescence
      intensity as apparent in the steady-state measurements.

PMID- 9521122
TI  - Comprehensive assessment of automatic structural alignment against a manual
      standard, the scop classification of proteins.
AB  - We apply a simple method for aligning protein sequences on the basis of a 3D
      structure, on a large scale, to the proteins in the scop classification of fold
      families. This allows us to assess, understand, and improve our automatic method
      against an objective, manually derived standard, a type of comprehensive
      evaluation that has not yet been possible for other structural alignment
      algorithms. Our basic approach directly matches the backbones of two structures,
      using repeated cycles of dynamic programming and least-squares fitting to
      determine an alignment minimizing coordinate difference. Because of simplicity,
      our method can be readily modified to take into account additional features of
      protein structure such as the orientation of side chains or the location
      dependent cost of opening a gap. Our basic method, augmented by such
      modifications, can find reasonable alignments for all but 1.5% of the known
      structural similarities in scop, i.e., all but 32 of the 2,107 superfamily pairs.
      We discuss the specific protein structural features that make these 32 pairs so
      difficult to align and show how our procedure effectively partitions the
      relationships in scop into different categories, depending on what aspects of
      protein structure are involved (e.g., depending on whether or not consideration
      of side-chain orientation is necessary for proper alignment). We also show how
      our pairwise alignment procedure can be extended to generate a multiple alignment
      for a group of related structures. We have compared these alignments in detail
      with corresponding manual ones culled from the literature. We find good agreement
      (to within 95% for the core regions), and detailed comparison highlights how
      particular protein structural features (such as certain strands) are
      problematical to align, giving somewhat ambiguous results. With these
      improvements and systematic tests, our procedure should be useful for the
      development of scop and the future classification of protein folds.

PMID- 9521121
TI  - Chemical synthesis and structural characterization of the RGD-protein decorsin: a
      potent inhibitor of platelet aggregation.
AB  - Decorsin is a 39-residue RGD-protein crosslinked by three disulfide bridges
      isolated from the leech Macrobdella decora belonging to the family of GPIIb-IIIa
      antagonists and acting as a potent inhibitor of platelet aggregation. Here we
      report the solid-phase synthesis of decorsin using the Fmoc strategy. The crude
      polypeptide was purified by reverse-phase HPLC in its reduced form and allowed to
      refold in the presence of glutathione. The homogeneity of the synthetic oxidized
      decorsin was established by reverse-phase HPLC and capillary zone
      electrophoresis. The results of amino acid analysis after acid hydrolysis of the
      synthetic protein, NH2-terminal sequencing and mass determination (4,377 Da) by
      electrospray mass spectrometry were in full agreement with this theory. The
      correct pairing of the three disulfide bridges in synthetic decorsin was
      determined by a combined approach of both peptide mapping using proteolytic
      enzymes and analysis of the disulfide chirality by CD spectroscopy in the near-UV
      region. Synthetic decorsin inhibited human platelet aggregation with an IC50 of
      approximately 0.1 microM, a figure quite similar to that determined utilizing
      decorsin from natural source. In particular, the synthetic protein was 2,000-fold
      more potent than a model RGD-peptide (e.g., Arg-Gly-Asp-Ser) in inhibiting
      platelet aggregation. Thermal denaturation experiments of synthetic decorsin,
      monitored by CD spectroscopy, revealed its high thermal stability (Tm
      approximately 74 degrees C). The features of the oxidative refolding process of
      reduced decorsin, as well as the thermal stability of the oxidized species, were
      compared with those previously determined for the NH2-terminal core domain
      fragment 1-41 or 1-43 from hirudin. This fragment shows similarity in size,
      pairing of the three disulfides and three-dimensional structure with those of
      decorsin, even if very low sequence similarity. It is suggested that the less
      efficient oxidative folding and the enhanced thermal stability of decorsin in
      respect to those of hirudin core domain likely can be ascribed to the presence of
      the six Pro residues in the decorsin chain, whereas none is present in the
      hirudin domain. The results of this study indicate that decorsin can be obtained
      by solid-phase methodology in purity and quantities suitable for structural and
      functional studies and thus open the way to prepare by chemical methods novel
      decorsin derivatives containing unusual amino acids or even non-peptidic
      moieties.

PMID- 9521124
TI  - Stability and folding properties of a model beta-sheet protein, Escherichia coli
      CspA.
AB  - Although beta-sheets represent a sizable fraction of the secondary structure
      found in proteins, the forces guiding the formation of beta-sheets are still not
      well understood. Here we examine the folding of a small, all beta-sheet protein,
      the E. coli major cold shock protein CspA, using both equilibrium and kinetic
      methods. The equilibrium denaturation of CspA is reversible and displays a single
      transition between folded and unfolded states. The kinetic traces of the
      unfolding and refolding of CspA studied by stopped-flow fluorescence spectroscopy
      are monoexponential and thus also consistent with a two-state model. In the
      absence of denaturant, CspA refolds very fast with a time constant of 5 ms. The
      unfolding of CspA is also rapid, and at urea concentrations above the
      denaturation midpoint, the rate of unfolding is largely independent of urea
      concentration. This suggests that the transition state ensemble more closely
      resembles the native state in terms of solvent accessibility than the denatured
      state. Based on the model of a compact transition state and on an unusual
      structural feature of CspA, a solvent-exposed cluster of aromatic side chains, we
      propose a novel folding mechanism for CspA. We have also investigated the
      possible complications that may arise from attaching polyhistidine affinity tags
      to the carboxy and amino termini of CspA.

PMID- 9521125
TI  - The early folding kinetics of apomyoglobin.
AB  - The folding pathway of apomyoglobin has been experimentally shown to have early
      kinetic intermediates involving the A, B, G, and H helices. The earliest detected
      kinetic events occur on a ns to micros time scale. We show that the early folding
      kinetics of apomyoglobin may be understood as the association of nascent helices
      through a network of diffusion-collision-coalescence steps G + H <--> GH + A <-->
      AGH + B <--> ABGH obtained by solving the diffusion-collision model in a chemical
      kinetics approximation. Our reproduction of the experimental results indicates
      that the model is a useful way to analyze folding data. One prediction from our
      fit is that the nascent A and H helices should be relatively more helix-like
      before coalescence than the other apomyoglobin helices.

PMID- 9521123
TI  - A conserved deamidation site at Asn 2 in the catalytic subunit of mammalian cAMP
      dependent protein kinase detected by capillary LC-MS and tandem mass
      spectrometry.
AB  - The N-terminal sequence myr-Gly-Asn is conserved among the myristoylated cAPK
      (protein kinase A) catalytic subunit isozymes Calpha, Cbeta, and Cgamma. By
      capillary LC-MS and tandem MS, we show that, in approximately one third of the
      Calpha and Cbeta enzyme populations from cattle, pig, rabbit, and rat striated
      muscle, Asn 2 is deamidated to Asp 2. This deamidation accounts for the major
      isoelectric variants of the cAPK C-subunits formerly called CA and CB.
      Deamidation also includes characteristic isoaspartate isomeric peptides from
      Calpha and Cbeta. Asn 2 deamidation does not occur during C-subunit preparation
      and is absent in recombinant myristoylated Calpha (rCalpha) from Escherichia
      coli. Deamidation appears to be the exclusive pathway for introduction of an
      acidic residue adjacent to the myristoylated N-terminal glycine, verified by the
      myristoylation negative phenotype of an rCalpha(Asn 2 Asp) mutant. This is the
      first report thus far of a naturally occurring myr-Gly-Asp sequence. Asp 2 seems
      to be required for the well-characterized (auto)phosphorylation of the native
      enzyme at Ser 10. Our results suggest that the myristoylated N terminus of cAPK
      is a conserved site for deamidation in vivo. Comparable myr-Gly-Asn sequences are
      found in several signaling proteins. This may be especially significant in view
      of the recent knowledge that negative charges close to myristic acid in some
      proteins contribute to regulating their cellular localization.

PMID- 9521126
TI  - GENFOLD: a genetic algorithm for folding protein structures using NMR restraints.
AB  - We report the development and validation of the program GENFOLD, a genetic
      algorithm that calculates protein structures using restraints obtained from NMR,
      such as distances derived from nuclear Overhauser effects, and dihedral angles
      derived from coupling constants. The program has been tested on three proteins:
      the POU domain (a small three-helix DNA-binding protein), bovine pancreatic
      trypsin inhibitor (BPTI), and the starch-binding domain from Aspergillus niger
      glucoamylase I, a 108-residue beta-sheet protein. Structures were calculated for
      each protein using published NMR restraints. In addition, structures were
      calculated for BPTI using artificial restraints generated from a high-resolution
      crystal structure. In all cases the fittest calculated structures were close to
      the target structure, and could be refined to structures indistinguishable from
      the target structures by means of a low-temperature simulated annealing
      refinement. The effectiveness of the program is similar to that of distance
      geometry and simulated annealing methods, and it is capable of using a very wide
      range of restraints as input. It can thus be readily extended to the calculation
      of structures of large proteins, for which few NOE restraints may be available.

PMID- 9521127
TI  - High level, context dependent misincorporation of lysine for arginine in
      Saccharomyces cerevisiae a1 homeodomain expressed in Escherichia coli.
AB  - The Saccharomyces cerevisiae a1 homeodomain is expressed as a soluble protein in
      Escherichia coli when cultured in minimal medium. Nuclear magnetic resonance
      (NMR) spectra of previously prepared a1 homeodomain samples contained a subset of
      doubled and broadened resonances. Mass spectroscopic and NMR analysis
      demonstrates that the heterogeneity is largely due to a lysine misincorporation
      at the arginine (Arg) 115 site. Arg 115 is coded by the 5'-AGA-3' sequence, which
      is quite rare in E. coli genes. Lower level mistranslation at three other rare
      arginine codons also occurs. The percentage of lysine for arginine
      misincorporation in a1 homeodomain production is dependent on media composition.
      The dnaY gene, which encodes the rare 5'-AGA-3' tRNA(ARG), was co-expressed in E.
      coli with the a1-encoding plasmid to produce a homogeneous recombinant a1
      homeodomain. Co-expression of the dnaY gene completely blocks mistranslation of
      arginine to lysine during a1 overexpression in minimal media, and homogeneous
      protein is produced.

PMID- 9521129
TI  - Purification and crystallization of the CDK-associated protein phosphatase KAP
      expressed in Escherichia coli.
AB  - The kinase associated phosphatase (KAP) is a human dual specificity protein
      phosphatase that dephosphorylates the cell cycle control protein, cyclin
      dependent kinase-2 on Thr 160 in a cyclin dependent manner (Poon & Hunter, 1995).
      We report here the over-expression of KAP in Escherichia coli as an N-terminal
      His-tagged protein using a modified pET-28a T7-expression vector. The recombinant
      protein was purified to homogeneity and crystallized. The crystals diffract to
      2.3 A resolution when exposed to synchrotron radiation and belong to space group
      P6(1)22, or its enantiomorph P6(5)22, with unit cell dimensions a = b = 74.5 A, c
      = 139.5 A.

PMID- 9521128
TI  - The importance of dynamic light scattering in obtaining multiple crystal forms of
      Trypanosoma brucei PGK.
AB  - Phosphoglycerate kinase (PGK) catalyzes the phosphoryl transfer between 1,3 bis
      phosphoglycerate and ADP to form 3-phosphoglycerate and ATP, undergoing
      significant conformational changes during catalysis. To more precisely document
      this reaction and the corresponding conformational changes, we have crystallized
      Trypanosoma brucei PGK in several crystal forms: (1) in the presence of 3
      phosphoglycerate and MgADP, PGK crystallizes with four molecules in the
      asymmetric unit; (2) in the presence of the ATP analog, AMP-PNP, PGK crystallizes
      in a similar form; (3) in the presence of the bisubstrate analog, adenylyl
      1,1,5,5-tetrafluoropentane-1,5-bisphosphonate, PGK crystals grow with one
      molecule in the asymmetric unit. Large scale expression and purification of T.
      brucei PGK from an E. coli overexpression system was required to obtain
      sufficient enzyme yields. Results from dynamic light scattering experiments
      allowed us to identify substrates and analogs which were amenable for
      crystallization. Ease of crystal growth and diffraction quality for a particular
      PGK-ligand complex is highly consistent with the apparent monodispersity of the
      complex in solution as judged by dynamic light scattering. The three-dimensional
      structures of the various enzyme-ligand complexes are currently being exploited
      to obtain a better understanding of PGK catalysis, as well as for structure based
      design of enzyme inhibitors to be used in the development of anti-trypanosomal
      agents.

PMID- 9521131
TI  - A revisit to bacterial protein synthesis: the search for the role of GTP.

PMID- 9521130
TI  - A LexA mutant repressor with a relaxed inter-domain linker.
AB  - The LexA protein is part of a large family of prokaryotic transcriptional
      repressors that contain an amino-terminal DNA binding domain and a carboxy
      terminal dimerization domain. These domains are separated by a linker or hinge
      region, which is generally considered to be rather flexible and unconstrained. So
      far, no structure of any of the full-length repressors is available. Here we show
      that a mutant LexA repressor harboring several point mutations in the hinge
      region gets sensitive to trypsin and Glu-C cleavage over a segment of at least 20
      amino acids, whereas the LexA wild-type hinge region is resistant to these
      proteases. These data are not compatible with the hypothesis of an fully flexible
      and/or unstructured inter-domain linker and suggest that the LexA hinge region
      is, in fact, constrained by contacts with the carboxy-terminal domain and/or a
      fairly stable local structure of the linker region.

PMID- 9521132
TI  - The different binding patterns of two immunoglobulin M monoclonal antibodies to
      Cryptococcus neoformans serotype A and D strains correlate with serotype
      classification and differences in functional assays.
AB  - Cryptococcus neoformans var. neoformans strains have historically been divided
      into serotypes A and D on the basis of reactivity with rabbit sera. Previously,
      we noted that two murine immunoglobulin M monoclonal antibodies (MAbs) to the
      capsular glucuronoxylomannan produced different indirect immunofluorescence (IF)
      patterns, described as annular and punctate, when bound to C. neoformans cells
      from different strains. In this study, we examined the reactivity of these two
      MAbs, known as 12A1 and 13F1, with 20 C. neoformans var. neoformans strains, of
      which 13 were serotype A and 7 were serotype D. For all strains, MAb binding was
      studied by IF and agglutination assays. In addition, we blindly tested the IF
      patterns of 22 C. neoformans var. neoformans strains. For selected strains, MAb
      binding was studied by flow cytometry (FACScan) and phagocytosis assays. The
      epitopes recognized by MAbs 12A1 and 13F1 were found in all of the strains. MAb
      12A1 binding produced an annular IF pattern with all of the strains, irrespective
      of the serotype classification. MAb 13F1 binding produced annular binding with
      all of the serotype A strains and punctate binding with 19 of 20 serotype D
      strains. In general, the punctate IF pattern was associated with lower
      fluorescence intensity, a requirement for higher antibody concentrations to
      produce yeast cell agglutination, and lower opsonic efficacy. Our results provide
      strong support for the existing classification of two serological types for
      strains assigned to variety neoformans and indicate qualitative and quantitative
      antigenic differences among serotype A and D strains.

PMID- 9521133
TI  - Evaluation of an immunoglobulin G enzyme-linked immunosorbent assay for pertussis
      toxin and filamentous hemagglutinin in diagnosis of pertussis in Senegal.
AB  - The enzyme-linked immunosorbent assay is widely employed for the serological
      diagnosis of pertussis. It is generally concluded that a significant increase in
      specific immunoglobulin G (IgG) or IgA against the pertussis toxin (PT) or
      against filamentous hemagglutinin (FHA) in paired sera correlates with Bordetella
      pertussis infection. However, this type of diagnosis of pertussis has mainly been
      applied to unvaccinated children, with timely sampling of acute- and convalescent
      phase sera. In current practice and in epidemiological studies, such criteria are
      not always fulfilled. The aim of this study was to analyze the significance of
      decreases in IgG antibody titers against PT and FHA between paired sera observed
      in suspected cases of pertussis infection. Serological results from paired sera
      were available for 460 children experiencing at least 8 days of cough. An anti-PT
      IgG decrease was observed in 25% of the children, more frequently than the anti
      FHA IgG decrease. Fourteen percent of the serologic decreases were observed in
      children with culture-confirmed infection, and 59% of the decreases were observed
      in children with confirmation criteria according to World Health Organization
      recommendations. Most of the decreases were observed when serum samples were
      collected according to a standard recommended schedule. Serologic decreases were
      observed more frequently among vaccinated children than among unvaccinated
      children. This difference, which was highly significant (P < 0.00001), was
      explained by the different kinetics of the antibody responses between vaccinated
      and unvaccinated children. The importance of the antibody response for the
      evaluation of vaccine efficacy, namely a bias toward higher absolute vaccine
      efficacy when this response is not taken into account, is discussed. This study
      supports an earlier recommendation that a significant decrease in PT or FHA
      should be added to the diagnostic criteria for pertussis.

PMID- 9521134
TI  - Decline of measles-specific immunoglobulin M antibodies after primary measles,
      mumps, and rubella vaccination.
AB  - Detection of measles-specific immunoglobulin M (IgM) has become the standard
      diagnostic method for laboratory confirmation of measles. In outbreaks, the
      interpretation of an IgM-positive result can be complicated when persons with
      suspected measles receive a dose of measles vaccine as part of outbreak control
      measures. This investigation evaluated the decay of measles-specific IgM
      antibodies 1 to 4 months after primary vaccination with measles, mumps, and
      rubella vaccine (MMRII). Serum samples were obtained from 536 infants vaccinated
      when they were 15 months old as part of a study to assess primary and secondary
      measles vaccine failure. Sixty serum specimens per week were selected from
      specimens collected between 4 and 9 weeks after MMRII vaccination; all 176
      available serum specimens collected between 10 and > or = 16 weeks were included.
      Specimens were tested for the presence of measles-specific IgM by an antibody
      capture enzyme immunoassay. The proportion of IgM-positive specimens dropped from
      73% at 4 weeks after vaccination to 52% at 5 weeks after vaccination and then
      declined to 7% by 8 weeks after vaccination. Less than 10% of children remained
      IgM positive between 9 and 11 weeks. An IgM-negative result helps rule out the
      diagnosis of measles in a person with suspected infection and a history of recent
      vaccination. The interpretation of a positive IgM result from a person with a
      clinically suspected case of measles and a recent history of measles vaccination
      (especially within 8 weeks) is problematic, and the diagnosis of measles should
      be based on epidemiologic linkage to a confirmed case or on detection of wild
      type measles virus.

PMID- 9521135
TI  - vacA genotypes and genetic diversity in clinical isolates of Helicobacter pylori.
AB  - Genetic diversity in Helicobacter pylori strains may affect the function and
      antigenicity of virulence factors associated with bacterial infection and,
      ultimately, disease outcome. In this study, DNA diversity of H. pylori isolates
      was examined by analysis of vacA genotypes and by restriction fragment length
      polymorphism (RFLP) analysis of H. pylori-associated genes (vacA, cagA,flaA,
      ureAB, and ureCD). Thirty-seven H. pylori isolates from 26 patients were
      successfully classified into distinct vacA allelic genotypes. The signal sequence
      allele sl (31 of 37) predominated over the s2 allele (6 of 37) and was
      significantly associated with the occurrence (past or present) of gastric ulcers.
      A novel midregion allele, designated as m3, has been identified in two H. pylori
      isolates which could not be typed with midregion allele m1- or m2-specific
      primers. Additionally, significant nucleotide diversity yielding different amino
      acid sequences was demonstrated by DNA sequencing of vacA fragments from clinical
      isolates of H. pylori. Furthermore, RFLP analysis of 45 H. pylori isolates
      (including 15 paired isolates) obtained from antrum and corpus biopsy specimens
      from 30 individual patients showed remarkably high interhost diversity (one
      patient, one H. pylori strain) and intrahost identity in gene sequences coding
      for VacA, CagA, flagellin, and urease. Only in a single patient was a minor
      genotypic variation at different anatomic sites within the stomach identified.
      These data warrant the detailed analysis of the effect of genetic diversity on
      the function and antigenicity of H. pylori-associated virulence factors.

PMID- 9521136
TI  - Cryptococcus neoformans chemotyping by quantitative analysis of 1H nuclear
      magnetic resonance spectra of glucuronoxylomannans with a computer-simulated
      artificial neural network.
AB  - The complete assignment of the proton chemical shifts obtained by nuclear
      magnetic resonance (NMR) spectroscopy of de-O-acetylated glucuronoxylomannans
      (GXMs) from Cryptococcus neoformans permitted the high-resolution determination
      of the total structure of any GXM. Six structural motifs based on an alpha-(1-
      >3)-mannotriose substituted with variable quantities of 2-O-beta- and 4-O-beta
      xylopyranosyl and 2-O-beta-glucopyranosyluronic acid were identified. The
      chemical shifts of only the anomeric protons of the mannosyl residues served as
      structure reporter groups (SRG) for the identification and quantitation of the
      six triads present in any GXM. The assigned protons for the mannosyl residues
      resonated at clearly distinguishable positions in the spectrum and supplied all
      the information essential for the assignment of the complete GXM structure. This
      technique for assigning structure is referred to as the SRG concept. The SRG
      concept was used to analyze the distribution of the six mannosyl triads of GXMs
      obtained from 106 isolates of C. neoformans. The six mannosyl triads occurred
      singularly or in combination with one or more of the other triads. The
      identification and quantitation of the SRG were simplified by using a computer
      simulated artificial neural network (ANN) to automatically analyze the SRG region
      of the one-dimensional proton NMR spectra. The occurrence and relative
      distribution of the six mannosyl triads were used to chemotype C. neoformans on
      the basis of subtle variations in GXM structure determined by analysis of the SRG
      region of the proton NMR spectrum by the ANN. The data for the distribution of
      the six SRGs from GXMs of 106 isolates of C. neoformans yielded eight chemotypes,
      Chem1 through Chem8.

PMID- 9521137
TI  - Diversity of hemagglutination phenotypes among P-fimbriated wild-type strains of
      Escherichia coli in relation to papG allele repertoire.
AB  - Data regarding the hemagglutination (HA) patterns of the three variants (classes
      I, II, and III) of the Escherichia coli adhesin PapG are conflicting. These HA
      patterns usually have been assessed for each papG allele separately with
      recombinant strains in slide HA assays. We rigorously evaluated an alternative
      microtiter tray HA assay and then used it to assess the HA of four erythrocyte
      types (human A1P1 and OP1, rabbit, and sheep erythrocytes) by multiple wild-type
      E. coli strains representing the four naturally occurring combinations of the
      papG alleles, i.e., class I plus III, class III only, class II plus III, and
      class II only. The microtiter tray HA assay displayed significantly better
      reproducibility of intraobserver (83%) and interobserver (86%) results than did
      slide HA assays (39 and 73%, respectively). Novel findings from the study of 32
      wild-type P-fimbriated strains included reproducible determinations of phenotypic
      diversity among different papG categories, among strains within each papG
      category, and from day to day for individual strains. There was also substantial
      overlap of phenotypes between papG categories I plus III and III only and between
      II plus III and II only. A class III papG recombinant strain's HA pattern
      differed significantly from that of the wild-type class III strains. These data
      demonstrate that HA phenotypes of wild-type P-fimbriated E. coli strains can be
      reproducibly assessed by a microtiter HA assay and that they correspond broadly
      to papG genotype but in a more complex and varied fashion than previously
      recognized.

PMID- 9521138
TI  - Detection of antibodies to human immunodeficiency virus type 1 in oral fluids: a
      large-scale evaluation of immunoassay performance.
AB  - Paired serum and oral-fluid (OF) specimens (n = 4,448) were collected from blood
      donors and patients attending local sexually transmitted disease clinics in
      Trinidad and Tobago and the Bahamas and were tested for the presence of human
      immunodeficiency virus type 1 (HIV-1) antibodies. Sera were tested by Abbott AB
      HIV-1/HIV-2 (rDNA) enzyme immunoassay (EIA), and positive specimens were
      confirmed by Cambridge HIV-1 and HIV-2 Western blotting (WB). OF specimens were
      collected with the OraSure collection device and were tested by Murex GACELISA
      and by two EIAs from Organon Teknika (the Oral Fluid Vironostika HIV-1 Microelisa
      System [OTC-L] and the Vironostika HIV-1 Microelisa System [OTC-M]). EIA-reactive
      OF specimens were confirmed by miniaturized WB (OFWB). GACELISA detected all 474
      HIV-1 seropositive specimens (sensitivity, 100%). OTC-L detected 470 positive
      specimens (sensitivity, 99.2%), while OTC-M detected 468 positive specimens
      (sensitivity, 98.8%). Specificities ranged from 99.2 to 100% for the three
      assays. Concordance of OFWB with serum WB was 99.4%, and banding patterns
      determined by the two methods were similar. The immunoglobulin G (IgG)
      concentration of OF specimens ranged from 0.21 to 100 microg/ml, with a mean of
      17.1 microg/ml. Significant differences in OF IgG concentrations were observed
      between HIV antibody-positive and HIV antibody-negative persons (31.94 versus
      15.28 microg/ml, respectively [P < 0.0001]). These data further confirm the
      suitability of OF specimens for detection of HIV-1 antibodies. Currently
      available HIV-1 antibody assays provide sensitivities and specificities with OF
      specimens comparable to those achieved with serum specimens.

PMID- 9521139
TI  - Capsular serotype and antibiotic resistance of Streptococcus pneumoniae isolates
      in two Chilean cities.
AB  - We compared the incidence of nasopharyngeal colonization by Streptococcus
      pneumoniae, the serotypes causing mucosal and invasive diseases, and the
      antibiotic resistance of these strains in patients admitted to three large
      hospitals and children attending day care centers in two Chilean cities (Santiago
      and Temuco). The populations in both cities were similar in ethnic background,
      socioeconomic status, family size, and access to medical care. Significant
      differences in nasopharyngeal colonization rates, in serotypes causing
      infections, and in antibiotic resistance were found between the two cities. In
      children 0 to 2 years of age, 42% were colonized with S. pneumoniae in Santiago
      compared to 14% in Temuco. A total of 41 serotypes were identified in both
      Chilean cities studied. Six serotypes were found only in Santiago; 14 serotypes
      were found only in Temuco. Antibiotic-resistant serotypes 6A, 6B, 14, 19F, and
      23F were detected only in Santiago. We show that important differences in the
      incidence of nasopharyngeal carriage, infection, and S. pneumoniae serotypes can
      exist in similar populations in different areas of the same country. Our findings
      are relevant for prevention strategies, antibiotic usage, and vaccine design.

PMID- 9521140
TI  - Reactivity of sera from systemic lupus erythematosus and Sjogren's syndrome
      patients with peptides derived from human immunodeficiency virus p24 capsid
      antigen.
AB  - We have previously demonstrated that about one-third of patients with either
      Sjogren's syndrome (SS) or systemic lupus erythematosus (SLE) react to human
      immunodeficiency virus (HIV) p24 core protein antigen without any evidence of
      exposure to, or infection with, HIV itself. Herein, we further characterize the
      specificity of this reaction using enzyme-linked immunosorbent assay to peptides
      representing fragments of p24. Characteristic epitope-specific profiles were seen
      for SS and SLE patients. SS patients had significantly increased responses to
      peptides F (p24 amino acids 69 to 86) and H (amino acids 101 to 111) and
      diminished reactivity to peptides A (amino acids 1 to 16) and P (amino acids 214
      to 228). SLE patients had increased reactivity to peptides E (amino acids 61 to
      76), H, and P. Utilization of peptide P hyporeactivity as the criterion to select
      for SS patients results in a screen that is moderately sensitive (64%) and
      specific (79.3%). Adding hyperreactivity to one other peptide (F or H) as an
      additional criterion yields an expected decrease in sensitivity (to 41%) while
      increasing specificity (to 93.1%). All sera-reactive peptides from regions of
      known structure of HIV p24 were located in the apex of the p24 molecule. Thus,
      the specificity of the peptide reactivities described here indicates a specific
      pattern of a nonrandom cross-reactivity between HIV type 1 p24 and autoimmune
      sera which may be partially syndrome specific. The future focus of our work will
      be to optimize assays of the peptide as diagnostic tools.

PMID- 9521141
TI  - Immunodepression induced by Trypanosoma cruzi and mouse hepatitis virus type 3 is
      associated with thymus apoptosis.
AB  - Trypanosoma cruzi-infected mice show disturbance in the peripheral immune system
      such as polyclonal lymphocyte activation, autoantibody production, and
      immunosuppression of T lymphocytes. Previous observations in our laboratory
      showed that some stocks of T. cruzi can be contaminated with mouse hepatitis
      virus type 3 (MHV-3). Literature has shown that MHV-3 infection induces
      immunologic disorders characterized by thymic involution with marked cell
      depletion. However, the effects of interactions between MHV-3 and the parasite on
      the immune system are not well understood. In the present study specific-pathogen
      free CBA mice were inoculated with MHV-3, alone or associated with different
      stocks of T. cruzi. Concurrent murine virus infection resulted in increased
      pathogenicity of T. cruzi infection shown by profound thymic atrophy; loss of
      cortical thymocytes; depletion of Thy1.2+, CD4+, and CD8+ cells; enhancement of
      in situ labeling of nuclear DNA fragmentation; and eventually, death of the
      animals. Such lines of evidence show that the mechanism underlying this thymic
      atrophy is associated with apoptosis. These results also suggest that MHV-3 can
      account for the increased immunosuppression observed during experimental
      infection with the parasite.

PMID- 9521142
TI  - Rapid detection of antigenic diversity of Akabane virus isolates by dot
      immunobinding assay using neutralizing monoclonal antibodies.
AB  - Akabane (AKA) virus is an arthropod-borne virus belonging to the Simbu group of
      the genus Bunyavirus. Neutralizing monoclonal antibodies (MAbs) against AKA virus
      were prepared, and the neutralizing epitopes of the virus were defined by
      competitive binding assay. Five distinct antigenic domains were identified and
      were designated A, B, C, D, and E. Domains A and C consisted of two epitopes
      each. It was demonstrated that seven neutralizing epitopes exist on the G1
      glycoprotein of AKA virus. Dot immunobinding assays (DIAs) were performed with
      MAbs which recognize these seven neutralizing epitopes. The results were similar
      to those obtained by enzyme-linked immunosorbent assay. DIAs were performed using
      two Australian strains, one isolate from Taiwan, and isolates from Japan
      collected between the years 1959 and 1994, for a total of 63 isolates. The MAb
      response patterns were divided into five groups: the OBE-1 strain, the JaGAr39
      strain, the Iriki strain, a group which consisted of features between those of
      the JaGAr39 strain and Iriki strain groups, and a group which did not belong to
      any of these patterns. The isolates which showed patterns similar to that of the
      JaGAr39 strain were found mostly among the isolates collected in 1974 and 1990,
      and isolates with patterns of MAb responses similar to the pattern of the Iriki
      strain were found mostly in the 1985 isolates. Those showing patterns in between
      were found mostly around 1977, 1987, and 1994. The results show that DIA can be
      used to effectively compare the antigenicities of AKA virus isolates within a few
      hours, even with lesser amounts of virus culture than is required for other
      assays.

PMID- 9521143
TI  - Evaluation of previously assigned antibody concentrations in pneumococcal
      polysaccharide reference serum 89SF by the method of cross-standardization.
AB  - An enzyme-linked immunosorbent assay (ELISA) and the antibody concentrations
      assigned to different pneumococcal capsular polysaccharide types were used to
      estimate concentrations of antibody to additional pneumococcal types in reference
      serum 89SF and to confirm assigned antibody values. This was possible because the
      slopes of curves of antibody binding to all polysaccharide types evaluated (1, 3,
      4, 5, 6B, 7F, 9V, 14, 18C, 19F, and 23F) were similar. The point estimates for
      total anti-pneumococcal antibody and immunoglobulin G (IgG) antibody determined
      by cross-standardization by an ELISA based on use of methylated human serum
      albumin (mHSA) to improve the efficiency of polysaccharide binding to the ELISA
      plate differed by less than 40% from those reported by Quataert et al. (Clin.
      Diagn. Lab. Immunol. 2:590-597, 1995) for types 1, 4, 6B, 7F, 9V, 14, 18C, and
      23F. However, large differences were found between the assigned values and those
      obtained by our mHSA ELISA for types 3 and 19F. The mHSA ELISA and the direct
      polysaccharide coat ELISA may not measure antibodies to the same epitopes on
      polysaccharides of types 3 and 19F. The functional importance of these different
      antibody specificities is being investigated. We have thus confirmed the assigned
      IgG antibody values for most types by a different method and have extended
      antibody assignments to several additional types.

PMID- 9521144
TI  - Immunoreactivity of five monoclonal antibodies against the 37-kilodalton common
      cell wall protein (PsaA) of Streptococcus pneumoniae.
AB  - Five monoclonal antibodies (MAbs) were produced against the Streptococcus
      pneumoniae pneumococcal surface adhesin A (PsaA) 37-kDa common cell wall protein.
      These antibodies were used in a dot immunoblot and Western blot study of clinical
      isolates of S. pneumoniae to detect the presence of the protein. By both assays,
      the MAbs reacted with clinical isolates representing the 23 type-specific
      serotypes present in the licensed pneumococcal polysaccharide vaccine. Western
      blot analysis confirmed the presence of a protein migrating in the gel with a
      molecular mass of 37 kDa. An extension of the study by using dot immunoblot
      analysis that included an analysis of the 90 serotypes of S. pneumoniae showed
      that all five MAbs reacted with 89 of the 90 serotypes tested. MAb 1B6, the
      exception, did not react with S. pneumoniae serotype 16F. Dot immunoblot analysis
      of the MAbs with Enterococcus faecalis and viridans streptococci showed varied
      reactivity patterns, depending on the species. The MAbs against the 37-kDa
      antigen did not react with Escherichia coli, respiratory pathogens, or
      nonpathogens representing 22 genera and 29 species of bacteria. All five MAbs
      also reacted with five multidrug-resistant strains of S. pneumoniae. In summary,
      these MAbs may be useful for detection of pneumococcal antigen and may lead to
      the development of diagnostic assays for pneumococcal disease.

PMID- 9521145
TI  - Involvement of antilipoarabinomannan antibodies in classical complement
      activation in tuberculosis.
AB  - We examined alternative and classical complement activation induced by whole
      bacilli of Mycobacterium bovis BCG and Mycobacterium tuberculosis products. After
      exposure to BCG, there were higher levels of the terminal complement complex in
      sera from Indian tuberculosis patients than in sera from healthy controls. The
      addition of BCG with or without EGTA to these sera indicated that approximately
      70 to 85% of the total levels of the terminal complement complex was formed by
      classical activation. Sera from Indian tuberculosis patients contained more
      antibody to lipoarabinomannan (LAM) than sera from healthy Indians. Levels of
      anti-LAM immunoglobulin G2 (IgG2), but not anti-LAM IgM, correlated positively
      with classical activation induced by BCG in the sera. By flow cytometry,
      deposition of C3 and terminal complement complex on bacilli incubated with normal
      human serum was demonstrated. The anticomplement staining was significantly
      reduced in the presence of EGTA and EDTA. Flow cytometry also revealed the
      binding of complement to BCG incubated with rabbit anti-LAM and then with factor
      B-depleted serum. This indicates that classical activation plays a major role in
      complement activation induced by mycobacteria and that anti-LAM IgG on the
      bacilli can mediate this response. Classical complement activation may be
      important for the extent of phagocytosis of M. tuberculosis by mononuclear
      phagocytes, which may influence the course after infection.

PMID- 9521147
TI  - Lipopolysaccharide from nonvirulent Ara+ Burkholderia pseudomallei isolates is
      immunologically indistinguishable from lipopolysaccharide from virulent Ara-
      clinical isolates.
AB  - Different lines of evidence suggest that a discrepancy between the distribution
      of Burkholderia (Pseudomonas) pseudomallei in the environment and the
      distribution of the disease melioidosis is attributable, at least in part, to
      phenotypic differences between clinical and some environmental isolates. Two
      antigenically and biochemically distinct biotypes have been described, only one
      of which is virulent. In this study, lipopolysaccharides (LPSs) were extracted by
      the proteinase K digestion method from a total of 214 B. pseudomallei isolates,
      and their immunoreactivities with sera from patients with different clinical
      spectra and with other infections were evaluated. With the exception of4 isolates
      from a total of 214 tested, the sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis silver-staining profiles of the LPSs from the two biotypes showed
      identical ladder patterns that were typical for smooth LPSs from other gram
      negative bacteria. The 210 isolates with typical LPS patterns (119 Ara- clinical,
      13 Ara- soil, 70 Ara+ soil, and 8 reference National Type Culture Collection
      strains) also exhibited similar immunoblot profiles against pooled sera from
      patients with melioidosis and hyperimmune mouse sera. Concordant findings were
      noted in the indirect enzyme-linked immunosorbent assay with Ara- and Ara+ LPSs
      to coat the microtiter plates. The LPSs of the different B. pseudomallei biotypes
      appear antigenically indistinguishable. It is, therefore, unlikely that this
      component is related to the virulence and pathogenicity of B. pseudomallei.

PMID- 9521146
TI  - Blinded multiplex PCR analyses of middle ear and nasopharyngeal fluids from
      chinchilla models of single- and mixed-pathogen-induced otitis media.
AB  - Multiplex PCR analyses for both bacterial and viral pathogens were conducted in a
      blinded manner on 33 archival specimens, of known culture status, procured from
      chinchilla models of both single- and mixed-pathogen-induced otitis media and
      from a pediatric patient. These specimens had been maintained at -70 degrees C
      for up to 6 years. Experimental specimens evaluated included middle-ear
      effusions, nasopharyngeal lavage fluids and middle-ear lavage fluids from animals
      which were immunologically naive, sham-immunized or actively immunized with
      nontypeable Haemophilus influenzae antigens. Sampling times used ranged from the
      day of bacterial or viral challenge to 42 days after challenge. Initial PCR
      analyses of the 33 specimens matched the traditional culture data in 24 instances
      (73%), correctly identifying nontypeable H. influenzae, Moraxella catarrhalis,
      Streptococcus pneumoniae, or adenovirus as the causative agent. A PCR-positive
      signal for the microbe(s) inoculated was also obtained in four animal model
      specimens (12%) which were culture negative. One of two culture-negative human
      effusions was also PCR positive. Thus, overall, results obtained by blinded PCR
      were 85% concordant with traditional culture methods or correctly indicated the
      specific pathogen introduced in four specimens that were sterile. In no instance
      was a false-positive signal obtained for any of the five etiologic agents being
      evaluated. We conclude that the multiplex PCR analyses are rapid and accurate
      methodologies when they are used to retrospectively evaluate diverse archival
      specimens of limited volume from experimental models of otitis media.

PMID- 9521148
TI  - Apoptosis in cord blood T lymphocytes from infants of human immunodeficiency
      virus-infected mothers.
AB  - Apoptosis continues to be controversial in human immunodeficiency virus (HIV)
      induced pathogenesis. To investigate whether apoptosis occurs with HIV exposure
      with or without subsequent infection, levels of apoptosis were measured in cord
      blood lymphocytes (CBL) from seven newborns delivered to HIV-infected mothers and
      seven normal, unexposed newborns. Live cells were costained with antibodies to
      cell surface markers and the DNA dye 7-amino actinomycin D to immunophenotype
      apoptotic CBL subsets. Apoptosis was measured in fresh and cultured CBL in the
      presence and absence of CD3 T-cell receptor stimulation. Compared to the CD4+ CBL
      from HIV-unexposed newborns, CD4+ CBL from six HIV-exposed, noninfected newborns
      demonstrated significantly greater apoptosis after overnight culture even in the
      absence of CD3 stimulation. Compared to HIV-unexposed controls, CD8+ CBL from the
      six HIV-exposed newborns also demonstrated increased levels of apoptosis after
      overnight culture without stimulation. The one HIV-infected newborn in this study
      showed the highest levels of CD4+ and CD8+ apoptotic CBL. The data suggest that
      levels of apoptosis are increased in infants in association with HIV infection.
      Furthermore, CD4+ and CD8+ cord blood lymphocytes from HIV-exposed infants
      behaved differently than T lymphocytes from either normal, unexposed infants or
      an HIV-infected infant. These results suggest that exposure to HIV or HIV-induced
      factors increases the levels of apoptosis in CBL.

PMID- 9521149
TI  - AIDS vaccination studies using an ex vivo feline immunodeficiency virus model:
      homologous erythrocytes as a delivery system for preferential immunization with
      putative protective antigens.
AB  - Feline immunodeficiency virus (FIV) is a useful model for testing of criteria for
      AIDS vaccine development. In the protocol we adopted, we used a primary isolate
      of FIV as a source of antigen and, for challenge, plasma from cats infected with
      the homologous virus never passaged in vitro. Cat erythrocytes (RBC) were coated
      with the surface components of freshly harvested and purified FIV by means of
      biotin-avidin-biotin bridges and used to immunize specific-pathogen-free cats
      (four doses at monthly intervals; total amount of FIV antigen administered per
      cat, approximately 14 microg). Immunized cats developed moderate levels of
      antibodies directed mainly to surface components of the virion and clearly
      evident lymphoproliferative responses. Four months after the last dose of
      immunogen, FIV-immunized cats and control cats immunized with bovine serum
      albumin-coated RBC were challenged. Judged from the results of the subsequent 12
      month follow-up, FIV-immunized cats exhibited at least some degree of protection.
      However, following rechallenge, most of the FIV-immunized animals became virus
      positive in spite of a booster immunogen dose given 2 months before the second
      challenge.

PMID- 9521150
TI  - Development of a blocking enzyme-linked immunosorbent assay for detection of
      serum antibodies to O157 antigen of Escherichia coli.
AB  - The O157 antigen of Escherichia coli shares structural elements with
      lipopolysaccharide (LPS) antigens of other bacterial species, notably Brucella
      abortus and Yersinia enterocolitica 09, a fact that confounds the interpretation
      of assays for anti-O157 antibodies. To address this problem, a blocking enzyme
      linked immunosorbent assay (bELISA) was designed with E. coli O157:H7 LPS as the
      antigen and a monoclonal antibody specific for E. coli O157, designated 13B3, as
      the competing antibody. The bELISA had equivalent sensitivity to, and
      significantly higher specificity than, the indirect ELISA (iELISA), detecting
      anti-O157 antibodies in sera from cattle experimentally inoculated with O157:H7.
      Only 13% of sera from naive heifers vaccinated for or experimentally infected
      with B. abortus had increased anti-O157 bELISA titers, while 61% of anti-O157
      iELISA titers were increased. The bELISA is a sensitive and specific method for
      the detection of serum antibodies resulting from exposure to E. coli O157.

PMID- 9521151
TI  - Kinetics of local and systemic immune responses to an oral cholera vaccine given
      alone or together with acetylcysteine.
AB  - The possibility that a mucolytic drug, i.e., acetylcysteine, given orally may
      enhance the gut mucosal or systemic immune response to an oral B-subunit-whole
      cell (B-WC) cholera vaccine was evaluated for 40 adult Swedish volunteers, and
      the kinetics of the immune responses were monitored for responding volunteers.
      Two doses of vaccine induced similar frequencies of immunoglobulin A (IgA) and
      IgG antitoxin responses (80 to 90%) and vibriocidal titer increases (60 to 65%)
      in serum irrespective of whether the vaccine was given alone or together with 2 g
      of acetylcysteine. In feces the frequencies of IgA antitoxin (67%) and
      antibacterial (33 to 40%) antibody responses were also comparable in the two
      immunization groups. Six months after vaccination, IgA and IgG antitoxin as well
      as vibriocidal antibody titer increases in serum could still be detected in
      approximately 80% of initially responding vaccinees. Significantly elevated fecal
      antitoxin and antibacterial IgA antibody levels were found in, respectively, 50
      and 43% of those volunteers who initially had responded to the vaccine.
      Determination of IgA antibodies in feces does not seem to offer any advantages
      compared to determination in serum for assessment of immune responses after
      immunization with inactivated cholera vaccine.

PMID- 9521152
TI  - Dehydroepiandrosterone sulfate treatment of mice modulates infection with
      Schistosoma mansoni.
AB  - Female mice treated with dehydroepiandrosterone sulfate early during infection
      were partially protected (P < 0.05-0.005) from Schistosoma mansoni infection.
      Hormone treatment did not modify parasite-specific cellular or humoral responses.
      Serum dehydroepiandrosterone sulfate levels and testosterone infection were
      negatively correlated, r = -0.621 and r = -0.653, respectively, with schistosome
      worm burden. The partial resistance to schistosome infection in
      dehydroepiandrosterone sulfate-treated female mice may be due to the known
      antischistosomular activity of testosterone.

PMID- 9521153
TI  - Use of trans-Sialidase inhibition assay in a population serologically negative
      for Trypanosoma cruzi but at a high risk of infection.
AB  - trans-Sialidase inhibition assay (TIA) was employed in a population at high risk
      of Trypanosoma cruzi infection. From 20 serum samples that were negative by
      conventional serologic and parasitologic assays, 18 (90%) were reactive in TIA,
      providing further evidence of the higher sensitivity of TIA and suggesting that
      the actual prevalence of T. cruzi infection might be underestimated.

PMID- 9521154
TI  - PCR detection of human cytomegalovirus DNA in clinical specimens using novel UL37
      exon 3 and US3 primers.
AB  - The sensitivity and specificity of novel UL37 exon 3 (UL37x3) and US3 immediate
      early (IE) gene PCR primers to detect human cytomegalovirus (HCMV) DNA in
      clinical specimens are comparable to those of HCMV DNA polymerase (UL54) primers.
      The use of these IE primers increases the diagnostic performance of HCMV PCR.

PMID- 9521156
TI  - A simple whole-blood test for detecting antibodies to human immunodeficiency
      virus.
AB  - We developed an immunochromatographic whole-blood test (WBT) which detects
      antibodies to human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2) from
      fingerstick blood. The sensitivity and specificity of the WBT were 99.41% (1,018
      confirmed positive patients) and 99.89% (941 uninfected patients), respectively
      (enzyme immunoassay [EIA] on serum or plasma as a reference). WBT performance was
      comparable to those of licensed EIAs and Western blotting, using 18 HIV-2 sera,
      23 HIV-1 seroconversion panels, and a low-titer performance panel (in lieu of
      whole blood).

PMID- 9521155
TI  - Evaluation of an enzyme-linked immunosorbent assay using recombinant major
      surface protein 5 for serological diagnosis of bovine anaplasmosis in Venezuela.
AB  - An indirect enzyme-linked immunosorbent assay (ELISA) was developed for the
      serological diagnosis of bovine anaplasmosis with purified recombinant major
      surface protein 5 (MSP5) of Anaplasma marginale produced in Escherichia coli.
      Serum antibody responses against MSP5 were detected in calves experimentally
      infected with A. marginale as early as 21 days postinfection and reached maximum
      titers at 28 days postinfection. The MSP5 ELISA performed with serum samples
      taken from field cattle from different regions of Venezuela showed a
      seroprevalence of 47%, which seems to be in accordance with the reported
      epidemiological status of bovine anaplasmosis in Venezuela. Positive results
      obtained in the MSP5 ELISA were further confirmed by immunoblotting, with the
      recombinant MSP5 as the antigen. Thus, these results confirmed the importance of
      MSP5 as a suitable antigen for the serological diagnosis of bovine anaplasmosis.

PMID- 9521157
TI  - Absolute CD4 counts obtained by a three-color flow-cytometric method without the
      use of a hematology analyzer.
AB  - We evaluated the Ortho TRIO-Cytoronabsolute system for determining absolute CD4
      counts. The CD4 counts in our blood specimens from 100 individuals ranged from 3
      to 1,962; the percent CD4 ranged from 1.3 to 62.2, respectively. The TRIO system
      was biased toward lower absolute counts than a combination of flow cytometry and
      hematology but showed no bias in percent CD4 calculations.

PMID- 9521158
TI  - Potential monitoring value of functional interleukin-2 receptors on human
      neutrophils.

PMID- 9521159
TI  - Tumor suppressor genes: does FHIT fit?

PMID- 9521160
TI  - Vitamins A and E: further clues for prostate cancer prevention.

PMID- 9521162
TI  - Using lasers and light-activated drugs, researchers home in on early lung
      cancers.

PMID- 9521161
TI  - Vitamin E reduces prostate cancer rates in Finnish trial: U.S. considers follow
      up.

PMID- 9521163
TI  - Infections and cancer: viruses are still prime suspects.

PMID- 9521164
TI  - Lessons from the tobacco wars edify nutrition war tactics.

PMID- 9521165
TI  - Maryland bill proposes mandated clinical trial coverage.

PMID- 9521166
TI  - Protein expression and functional analysis of the FHIT gene in human tumor cells.
AB  - BACKGROUND: The fragile histidine triad (FHIT) gene at chromosome 3p14.2 has been
      proposed to be a candidate tumor suppressor gene in human cancers. To test
      whether FHIT exhibits the functional properties of a tumor suppressor gene, we
      studied the expression of its protein (pFHIT) in human carcinoma cells and
      examined the ability of FHIT to inhibit the neoplastic phenotype of cancer cells.
      METHODS: Subcellular localization and patterns of protein expression in tumor
      cells were determined by immunohistochemical analysis and immunoblotting with the
      use of polyclonal anti-pFHIT antisera. In tumor cells with undetectable pFHIT, we
      examined the effect of recombinant pFHIT expression on morphology, growth rate,
      colony formation, and in vivo tumor formation. RESULTS: We demonstrated that
      pFHIT is a cytoplasmic 17-kd polypeptide whose expression could not be detected
      in 30 of 52 human carcinoma cell lines tested. We observed, however, that the
      stable overexpression of pFHIT did not alter cell morphology, inhibit colony
      formation, or inhibit cell proliferation in vitro. Furthermore, overexpression of
      pFHIT did not lead to altered cell cycle kinetics in dividing cells. The in vivo
      tumorigenicity of a tumor cell line that expressed high levels of recombinant
      pFHIT was equivalent to that of control transfectants and of parental cells.
      CONCLUSIONS: These results suggest that the replacement of pFHIT in human
      carcinoma cells does not suppress tumor cell growth and that this protein may be
      involved in tumorigenesis in ways that are distinct from the "classic" tumor
      suppressor paradigm.

PMID- 9521168
TI  - Prostate cancer and supplementation with alpha-tocopherol and beta-carotene:
      incidence and mortality in a controlled trial.
AB  - BACKGROUND: Epidemiologic studies have suggested that vitamin E and beta-carotene
      may each influence the development of prostate cancer. In the Alpha-Tocopherol,
      Beta-Carotene Cancer Prevention Study, a controlled trial, we studied the effect
      of alpha-tocopherol (a form of vitamin E) and beta-carotene supplementation,
      separately or together, on prostate cancer in male smokers. METHODS: A total of
      29133 male smokers aged 50-69 years from southwestern Finland were randomly
      assigned to receive alpha-tocopherol (50 mg), beta-carotene (20 mg), both agents,
      or placebo daily for 5-8 years (median, 6.1 years). The supplementation effects
      were estimated by a proportional hazards model, and two-sided P values were
      calculated. RESULTS: We found 246 new cases of and 62 deaths from prostate cancer
      during the follow-up period. A 32% decrease (95% confidence interval [CI] = -47%
      to -12%) in the incidence of prostate cancer was observed among the subjects
      receiving alpha-tocopherol (n = 14564) compared with those not receiving it (n =
      14569). The reduction was evident in clinical prostate cancer but not in latent
      cancer. Mortality from prostate cancer was 41% lower (95% CI = -65% to -1%) among
      men receiving alpha-tocopherol. Among subjects receiving beta-carotene (n =
      14560), prostate cancer incidence was 23% higher (95% CI = -4%-59%) and mortality
      was 15% higher (95% CI = -30%-89%) compared with those not receiving it (n =
      14573). Neither agent had any effect on the time interval between diagnosis and
      death. CONCLUSIONS: Long-term supplementation with alpha-tocopherol substantially
      reduced prostate cancer incidence and mortality in male smokers. Other controlled
      trials are required to confirm the findings.

PMID- 9521167
TI  - Abnormalities of fragile histidine triad genomic and complementary DNAs in
      cervical cancer: association with human papillomavirus type.
AB  - BACKGROUND: Chromosome 3p14.2 contains FRA3B, the most active chromosome breakage
      site in the human genome. The fragile histidine triad (FHIT) gene, a putative
      tumor suppressor gene, overlaps FRA3B. Human papillomavirus (HPV), a known
      cofactor in cervical carcinogenesis, can integrate into FRA3B. We examined
      abnormalities in FHIT and its RNA transcripts in cervical cancer cell lines and
      tumors. We also investigated the relationship between loss of heterozygosity
      (LOH) in FHIT/FRA3B and the presence of oncogenic HPV types. METHODS: Eleven cell
      lines, 40 tumors (20 fresh and 20 archival), and 10 normal cervical epithelia
      were examined. Two intragenic polymorphic markers (D3S1300 and D3S4103) and the
      polymerase chain reaction (PCR) were used to examine FHIT LOH. Reverse
      transcription-PCR (RT-PCR) analysis and single-strand conformation polymorphism
      analysis of RT-PCR products were used to characterize FHIT transcripts. Oncogenic
      HPV types were identified by PCR, using general and type-specific primers.
      RESULTS: All normal epithelia, 19 of 20 fresh tumors and nine of 11 cell lines
      expressed wild-type and, occasionally, exon 8-deleted FHIT transcripts.
      Additional aberrant FHIT transcripts were seen in nine of 20 fresh tumors and in
      seven of 11 cell lines. DNA sequencing of the aberrant transcripts revealed a
      variety of insertions and deletions but no point mutations. Three cell lines also
      had homozygous FHIT deletions. Oncogenic HPV types (i.e., 16, 18, 31, and 33)
      were detected in 18 of 20 archival tumors, and, in these tumors, LOH within FHIT
      was identified in nine of 16 informative cases. HPV 16 was found to be associated
      with LOH in the FHIT/FRA3B region (P = .041). CONCLUSION: FHIT/FRA3B is
      frequently altered in cervical cancer, demonstrating LOH, occasional homozygous
      deletions, and frequent aberrant transcripts not found in normal epithelia.
      However, the presence of wild-type transcripts and the lack of protein-altering
      point mutations raise questions about FHIT's function as a classic tumor
      suppressor gene in cervical tissue.

PMID- 9521169
TI  - Expression of angiogenesis-related genes and progression of human ovarian
      carcinomas in nude mice.
AB  - BACKGROUND: By the time patients are diagnosed with ovarian carcinoma, peritoneal
      dissemination of the tumor often has occurred. The progressive growth and spread
      of ovarian carcinoma depend, in part, on the formation of an adequate blood
      supply. We determined whether the expression of genes that regulate distinct
      steps in angiogenesis (i.e., the formation of new blood vessels) was associated
      with the pattern and progressive growth of human ovarian carcinomas implanted in
      the peritoneal cavity of nude mice. METHODS: Five different human ovarian
      carcinomas were injected individually into the peritoneal cavity of female NCr
      nu/nu nude mice. The expression of basic fibroblast growth factor, vascular
      endothelial growth factor/vascular permeability factor (VEGF/VPF), interleukin 8
      (IL-8), and collagenase type IV (MMP-2 [matrix metalloproteinase-2] and MMP-9)
      was determined by northern blot analysis, in situ hybridization of messenger RNA,
      and immunohistochemical analysis. Blood vessel distribution and density,
      macrophage infiltration pattern, and stromal reaction were determined by
      immunohistochemical analysis with specific antibodies. RESULTS: Three of the
      carcinomas produced both solid lesions and ascitic tumors, whereas the remaining
      two produced only solid lesions. Two of the carcinomas produced rapidly
      progressive disease, two produced slow disease, and one produced intermediate
      disease. The formation of ascites was directly associated with expression of
      VEGF/ VPF, and survival was inversely associated with expression of IL-8. In
      rapidly growing tumors, the number of blood vessels was high throughout the
      lesion; in contrast, in slow-growing tumors, most vessels (and infiltrating
      macrophages) were located at the periphery. CONCLUSIONS: The expression of
      various genes that regulate angiogenesis in human ovarian carcinomas is
      associated with the pattern of the disease and its progression. Therefore,
      targeting specific genes that regulate angiogenesis could offer new approaches to
      the treatment of ovarian cancer.

PMID- 9521171
TI  - Prediagnostic serum vitamin D and breast cancer.

PMID- 9521170
TI  - Expression of cyclooxygenase-1 and cyclooxygenase-2 in human breast cancer.
AB  - BACKGROUND: Numerous studies have demonstrated that the levels of prostaglandins
      are greater in various cancers, including breast cancer and colon cancer, than in
      normal tissues. In particular, the inducible form of cyclooxygenase (COX), the
      rate-limiting enzyme in prostaglandin biosynthesis, is overexpressed in colon
      tumors. Epidemiologic studies have demonstrated that the use of aspirin or other
      nonsteroidal anti-inflammatory drugs (NSAIDs) can reduce the risk of colon cancer
      and, to a lesser extent, the risk of breast cancer. NSAIDs are known to inhibit
      COX, suggesting that the beneficial effect of NSAIDs in colon cancer may be
      related to COX overexpression in this disease. This possibility led us to ask
      whether COX is also overexpressed in breast cancers. METHODS: Surgical specimens
      from 44 patients with breast cancer who had undergone lumpectomy or mastectomy
      were analyzed by immunoblot analysis and immunohistochemical analysis to
      determine the expression profile of the constitutively expressed form of
      cyclooxygenase (COX-1) and the inducible form (COX-2); the specimens from 14
      patients included normal breast tissue. RESULTS: Expression of COX-1 protein was
      substantially higher in 30 of 44 tumor samples than in any of the 14 normal
      tissue specimens. Immunoblot analysis revealed extremely high levels of COX-2
      protein in two tumor samples. Immunohistochemical staining of specimens that
      expressed COX-1 and/or COX-2 revealed that COX-1 was localized in stromal cells
      adjacent to the tumor but not in tumor cells. In contrast, COX-2 was localized
      primarily in tumor cells but also appeared in stromal cells. CONCLUSION: Our
      results suggest that overexpression of COX may not be unique to colon cancer and
      may be a feature common to other epithelial tumors.

PMID- 9521172
TI  - Re: Participation in colorectal cancer screening: a review.

PMID- 9521173
TI  - Re: Fecal occult blood screening in the Minnesota study.

PMID- 9521174
TI  - Re: Tamoxifen and chemotherapy for lymph node-negative, estrogen receptor
      positive breast cancer.

PMID- 9521175
TI  - Re: Benzene and the dose-related incidence of hematologic neoplasms in China.

PMID- 9521176
TI  - The genetic passport.

PMID- 9521177
TI  - Individual risk factors for hip osteoarthritis: obesity, hip injury, and physical
      activity.
AB  - Hip osteoarthritis is a major cause of pain and disability. The authors explored
      individual risk factors for hip osteoarthritis in a population-based case-control
      study. The study was performed in two English health districts (Portsmouth and
      North Staffordshire) from 1993 to 1995. A total of 611 patients (210 men and 401
      women) listed for hip replacement because of osteoarthritis over an 18-month
      period were compared with an equal number of controls selected from the general
      population and individually matched for age, sex, and family practitioner.
      Information about suspected risk factors was obtained by a questionnaire
      administered at interview and a short physical examination. Obesity (odds ratio
      (OR) = 1.7, 95% confidence interval (CI) 1.3-2.4; highest vs. lowest third of
      body mass index), previous hip injury (OR = 4.3, 95% CI 2.2-8.4), and the
      presence of Heberden's nodes (OR = 1.6, 95% CI 1.2-2.2) were independent risk
      factors for hip osteoarthritis among men and women. Hip injury was more closely
      related to unilateral as compared with bilateral disease. There were a negative
      association between cigarette smoking and osteoarthritis among men and a weak
      positive association with prolonged regular sporting activity. Obesity and hip
      injury are important independent risk factors for hip osteoarthritis, which might
      be amenable to primary prevention. Hip osteoarthritis may also arise as part of
      the polyarticular involvement found in generalized osteoarthritis.

PMID- 9521178
TI  - Osteoarthritis of the hip and occupational lifting.
AB  - To test the hypothesis that occupational lifting is a cause of hip
      osteoarthritis, the authors examined associations with lifting and other
      occupational activities in a case-control study. The study was performed in two
      English health districts (Portsmouth and North Staffordshire) from 1993 to 1995.
      A total of 611 patients (210 men and 401 women) listed for hip replacement
      because of osteoarthritis over an 18-month period were compared with an equal
      number of controls selected from the general population and individually matched
      for age, sex, and general practice. Information about suspected risk factors was
      obtained by a questionnaire administered at interview and a short physical
      examination. Analysis was by conditional logistic regression. After adjustment
      for potential confounders, the risk in men increased progressively with the
      duration and heaviness of occupational lifting. Relative to those with low
      exposure, men who had regularly lifted weights in excess of 50 kg for 10 years or
      longer had an odds ratio of 3.2 (95% confidence interval 1.6-6.5). No comparable
      association was found in women. Of the other occupational activities examined,
      only frequent climbing of stairs showed a pattern suggestive of a causal
      relation. These findings are consistent with the results of other studies, and
      there is now a strong case for regarding hip osteoarthritis as an occupational
      disease in men whose work has involved prolonged and frequent heavy lifting.

PMID- 9521179
TI  - Incidence and risk factors for self-reported peptic ulcer disease in the United
      States.
AB  - Incidence and risk factors for peptic ulcer disease in the United States have not
      been well defined. During the 1989 National Health Interview Survey, a population
      based sample of 42,392 individuals responded to questions regarding doctor
      diagnosed ulcers with confirmation by either an upper gastrointestinal series or
      endoscopy. Ulcers present during the previous 12 months were considered either
      incident ulcers if diagnosed during this period or chronic active ulcers if
      diagnosed more than 12 months before the interview. The incidence of ulcers over
      the year prior to the interview was 5.27 per 1,000 adults. Whereas incident
      duodenal ulcer cases represented only 2.4 percent of all persons with a history
      of duodenal ulcer, the corresponding value for gastric ulcer was 8.7 percent.
      Risk factors for incident ulcers included increasing age, lower income and
      educational attainment, and musculoskeletal pain or headache. These were similar
      to risk factors for chronic active ulcers, except smoking was an additional
      important risk factor for chronic active ulcers. Thus, incident peptic ulcers are
      common in the United States but represent a small proportion of persons with a
      history of ulcer disease. Smoking may be a stronger risk factor for chronic
      ulcers than for new ulcers.

PMID- 9521180
TI  - Personal sampling of particles in adults: relation among personal, indoor, and
      outdoor air concentrations.
AB  - To investigate the validity of outdoor particulate matter with a 50% cutoff
      diameter of 10-microm (PM10) concentrations as a measure of exposure in time
      series studies, the association between personal and outdoor concentrations,
      within subjects, over time was investigated. Repeated measurements of personal,
      indoor, and outdoor PM10 were conducted among 37 nonsmoking, 50- to 70-year-old
      adults, living in Amsterdam, Netherlands, 1994. Regression analyses were
      conducted for each subject separately, and the distribution of the individual
      regression and correlation coefficients was investigated. Furthermore, the extent
      to which differences among personal, indoor, and outdoor concentrations could be
      explained was studied. The median Pearson's R between personal and outdoor
      concentrations was 0.50. Excluding days with exposure to environmental tobacco
      smoke (ETS) improved the correlation to a median R of 0.71. The estimated cross
      sectional correlations were lower, 0.34 and 0.50, respectively. Outdoor
      concentrations (mean, 42 microg/m3) exceeded indoor concentrations (mean, 35
      microg/m3) but underestimated personal exposures (mean, 62 microg/m3). The major
      part of the difference between personal and outdoor concentrations could be
      attributed to exposure to ETS, living along a busy road, and time spent in a
      vehicle. The results show a reasonably high correlation between personal and
      outdoor PM10 within individuals, providing support for the use of ambient PM10
      concentrations as a measure of exposure in epidemiologic studies linking the day
      to-day variation in particulate matter air pollution to the day-to-day variation
      in health endpoints such as mortality, hospital admissions, respiratory symptoms,
      and lung function.

PMID- 9521181
TI  - Risk of cancer among Danish utility workers--a nationwide cohort study.
AB  - The authors report the incidence of cancer in a large cohort of employees
      identified from all 99 Danish utility companies. Personal data and information on
      employment and exposure to magnetic fields and asbestos were obtained from manual
      files at the companies, the Danish Supplementary Pension Fund, and the public
      payroll administration. A total of 32,006 individuals with more than 3 months of
      employment were linked with the files of the Danish Cancer Registry. The period
      of follow-up for cancer occurrence among the employees was from April 1968
      through December 1993 in the study conducted from 1994 to 1997. Overall, 3,008
      cancers were observed, with 2,825 expected, yielding a small but significantly
      increased risk of 1.06 (95% confidence interval 1.03-1.10) among the utility
      workers in comparison with the general population. No excess was observed for all
      leukemias or for cancers of the brain or breast among men or women. There was no
      association of electromagnetic field exposure with risk of these cancers, even
      when the level and length of exposure to magnetic fields were taken into account.
      Increased risks for cancers of the lung and pleural cavity were seen mainly for
      workers whose jobs involved exposure to asbestos. The results from this study do
      not support the hypothesis of an association between occupational exposures to
      magnetic fields in the electric utility industry and the risk for cancer.

PMID- 9521182
TI  - Validity of self-reported cancers in a prospective cohort study in comparison
      with data from state cancer registries.
AB  - The accuracy of self-reported cancer diagnoses in a prospective study was
      compared with population-based cancer registry data in four states. The study
      cohort included 65,582 men and women aged 39-96 years who were participants in
      the Cancer Prevention Study II Nutrition Survey, begun by the American Cancer
      Society in 1992. Estimates of sensitivity (the proportion of study participants
      with a registry-documented cancer who self-reported the cancer) ranged from 0.79
      for an exact match of cancer site and year of diagnosis (+/- 1 year) to 0.93 for
      a match of any reported cancer. The sensitivity of exact matches varied
      considerably by cancer site and was highest for breast, prostate, and lung
      cancers (0.91, 0.90, and 0.90, respectively) and lowest for rectal cancer and
      melanoma (0.16 and 0.53, respectively). Sensitivity also varied slightly by the
      age, education, and smoking status of study participants. Estimates of
      sensitivity were virtually identical for each of the four states. The positive
      predictive value (the proportion of self-reported cancers that were confirmed by
      the registries) was 0.75 overall and also varied by cancer site. Unlike
      sensitivity, however, this proportion varied considerably by state. All self
      reports of cancer that were not confirmed by the registries were further
      investigated by repeat questionnaires and acquisition of medical records. Low
      positive predictive values were due to underascertainment of true cancer cases by
      the registries, inaccurate reporting on the part of study participants, and
      problems with the algorithm used by the state to link the study population to the
      registry data. In conclusion, the ability of members of this cohort to report a
      past diagnosis of cancer accurately is quite high, especially for cancers of the
      breast, prostate, lung, and colon, or for the occurrence of any cancer.

PMID- 9521184
TI  - Incidence and risk of dementia. The Rotterdam Study.
AB  - To assess age-, sex-, and subtype-specific incidence rates of dementia and to
      calculate the risk of dementia, the authors performed a large, community-based,
      prospective cohort study on dementia as part of the Rotterdam Study. Participants
      were recruited among residents of a suburb of Rotterdam, aged 55 years and older.
      Baseline examinations took place between 1990 and 1993. The average follow-up was
      2.1 years. Screening for dementia followed a three-stage protocol. Medical
      records of subjects who had died or could not be examined in person were
      evaluated. Of 7,046 subjects who were nondemented at baseline, 162 developed
      dementia during 15,135 person-years of follow-up, resulting in an overall
      incidence rate of 10.7 per 1,000 person-years. From the youngest to the oldest 5
      year age category, the incidence rate increased from 0.6 to 97.2 per 1,000 person
      years. Only in men did the increase level off after age 85. Overall, the
      incidence rate per 1,000 person-years was 7.7 for Alzheimer's disease and 1.5 for
      vascular dementia. Dementia incidence rates and dementia-free Kaplan-Meier
      survival tables were used to calculate age- and sex-specific cumulative risks of
      dementia. Although the incidence rates of men and women up to age 85 were
      similar, the lifetime risk of dementia for 55-year-old women was twice as high as
      for men (0.33 vs. 0.16), reflecting both the higher life expectancy of women and
      the higher dementia risk at very old age.

PMID- 9521183
TI  - Body weight change and carotid artery wall thickness. The Atherosclerosis Risk in
      Communities (ARIC) Study.
AB  - The impact of weight change in adulthood on cardiovascular disease is
      controversial. This study examined the association of change in body weight, from
      young adulthood to middle age, with average carotid artery intimal-medial wall
      thickness by B-mode ultrasound measured in middle age. Participants were 13,282
      men and women aged 45-64 years from the baseline examination of the
      Atherosclerosis Risk in Communities (ARIC) Study (1987-1989). Weight change was
      calculated as the difference between weight at the baseline examination and self
      reported weight at age 25. White men gained a mean of 9.7 kg; black men, 10.1 kg;
      white women, 12.0 kg; and black women, 20.8 kg. Weight change was positively,
      albeit modestly, associated with intimal-medial thickness in black men and white
      men and in white women, but not in black women. Adjusted for age, examination
      center, smoking, education, sports activity level, height, and body mass index at
      age 25, the differences in intimal-medial thickness associated with a 10-kg
      increment in weight change were 0.016 (95% confidence interval 0.010 to 0.022) mm
      in white men, 0.008 (95% confidence interval 0.001 to 0.015) mm in black men,
      0.013 (95% confidence interval 0.009 to 0.017) mm in white women, and 0.002 (95%
      confidence interval -0.002 to 0.006) mm in black women. These findings support
      the hypothesis that weight gain in adulthood promotes atherosclerotic changes in
      white men and women and in black men.

PMID- 9521185
TI  - Are we underestimating rates of vaginal birth after previous cesarean birth? The
      validity of delivery methods from birth certificates.
AB  - Previous studies of birth certificates have not fully evaluated how accurately
      they identify delivery methods that have a historical component, such as repeat
      cesarean and vaginal birth after previous cesarean (VBAC). The authors used
      linked Georgia birth certificates for first and second deliveries to examine the
      accuracy of four reported delivery methods in the second pregnancy: vaginal
      (without previous cesarean), VBAC, primary cesarean, and repeat cesarean, as well
      as an indicator of a previous cesarean. From the immediate birth certificates,
      the delivery method for each of the two births was classified as vaginal (V) or
      cesarean section (CS), which produced possible sequences of V-V, CS-V, V-CS, and
      CS-CS. The delivery method for the second births to 106,049 women from 1989
      through 1992 was reviewed, taking into account the historical information from
      the linked certificates regarding the first births. Only 42.0% of women with a CS
      V sequence were correctly designated on the second birth certificate as a VBAC;
      79.3% of women with a V- CS sequence were correctly designated as primary
      cesarean. From 1980 through 1988, birth certificates contained a check box
      indicating a previous cesarean (but no VBAC box). During this period, only 75.5%
      of 25,491 women with a previous cesarean were so designated on the birth
      certificate. These findings suggest that cross-sectional vital records data
      substantially underestimate VBAC and primary cesarean rates.

PMID- 9521186
TI  - Agreement among indicators of vitamin C status.
AB  - Agreement among three indicators of vitamin C status--serum ascorbate level, a 24
      hour recall, and the frequency of fruit and vegetable consumption--was examined
      using data from the Second National Health and Nutrition Examination Survey
      conducted between 1976 and 1980. Agreement between pairs of these indicators was
      good when assessed at the group level but inconsistent at the individual level.
      These indicators, when classified as continuous measures, had moderately good
      agreement (r = 0.45-0.54), whereas agreement was poor when classified as
      quartiles (kappa = 0.17-0.23). Agreement between clinically based categories of
      serum ascorbate and total intake levels was poorer than expected (kappa = 0.25)
      as was agreement between low or deficient levels of both of these indicators
      (kappa = 0.3). Disagreement between low or deficient serum and intake levels was
      greater in participants who were younger, African American compared with white
      and other races, less educated, current smokers, nonsupplement users, and
      examined in the winter compared with in the summer or fall. These findings
      suggest that the indicators cannot be used interchangeably to assess vitamin C
      status because they distinguish between different aspects of status, intake level
      versus serum level, an indicator of available pool. Moreover, depending upon how
      these indicators are used in statistical analyses, they may classify individuals
      differently.

PMID- 9521187
TI  - A statistical model to identify the contaminated lots implicated in iatrogenic
      transmission of Creutzfeldt-Jakob disease among French human growth hormone
      recipients.
AB  - From 1970 to 1988, thousands of children have been treated with human growth
      hormone (hGH) to supply pituitary gland deficiency. In France, 51 of the 968
      children treated by hGH lots produced between January 1984 and March 1985 had
      developed Creutzfeldt-Jakob disease (CJD) by the end of 1996. The authors'
      objective was to investigate which of the 13 hGH lots produced during this period
      might be implicated in the iatrogenic transmission of CJD. In this paper, the
      authors describe a model that was developed to compute the probability for each
      lot of being contaminated. The validity of the model was assessed by a simulation
      study that showed a good agreement between the estimated and the simulated number
      of contaminated lots. The model suggested that about half of the lots distributed
      during this period might have been contaminated by the infectious agent that
      causes CJD. The risk of iatrogenic CJD for patients exposed to contaminated hGH
      lots was estimated to be 0.06 (95% confidence interval 0.05-0.07).

PMID- 9521188
TI  - Re: "Validated questionnaire for the identification of previous personal or
      familial venous thromboembolism".

PMID- 9521189
TI  - Re: "Assessment of surveillance for meningococcal disease in New York State,
      1991".

PMID- 9521190
TI  - Re: "Occupational risk factors for gastric cancer: an overview".

PMID- 9521191
TI  - Organ donor screening for infectious diseases: review of practice and
      implications for transplantation.

PMID- 9521192
TI  - Minor transplantation antigens: animal models for human host-versus-graft, graft
      versus-host, and graft-versus-leukemia reactions.

PMID- 9521193
TI  - Increased incidence of insulin-dependent diabetes mellitus in pediatric renal
      transplant patients receiving tacrolimus (FK506)
AB  - BACKGROUND: Use of tacrolimus (FK506), a potent immunosuppressive agent, has been
      reported to have a 10-20% incidence of insulin-dependent diabetes mellitus (IDDM)
      in adults, but the incidence of IDDM in pediatric renal transplant recipients
      treated with this agent is unknown. In this article, we report our single-center
      experience with FK506-induced IDDM in children. METHODS: Five consecutive living
      related donor pediatric renal transplants were reviewed retrospectively. RESULTS:
      All five patients developed IDDM lasting longer than 6 months. Mean follow-up
      time was 18.6 months. CONCLUSIONS: Pediatric patients may be at high risk for
      developing FK506-induced IDDM.

PMID- 9521194
TI  - Liver transplantation with cavoportal hemitransposition in the presence of
      diffuse portal vein thrombosis.
AB  - BACKGROUND: Orthotopic liver transplantation is possible even in the presence of
      recipient portal vein thrombosis, provided that hepatopetal portal flow to the
      graft can be restored. On rare occasions this is not possible due to diffuse
      thrombosis of the portal venous system. In these cases, successful liver
      transplantation has been considered impossible. Portocaval transposition was
      introduced in the pretransplantation era to study the effect of systemic venous
      flow on the liver and has been used in three patients for the treatment of
      glycogen storage disease. We used portocaval hemitransposition (portal perfusion
      with inflow from the inferior vena cava) in liver transplantation when portal
      inflow to the graft was not feasible. We are reporting the collective experience
      of nine patients from four liver transplant centers. METHODS: Cavoportal
      hemitransposition was used in nine patients. In seven of these cases, the
      technique was used during the original transplant (primary group). In two cases,
      it was used after the portal inflow to the first transplant had clotted
      (secondary group). RESULTS: Five of seven patients in the primary group are alive
      after intervals of 6-11 months. The two patients in the rescue group died. In the
      successful cases, liver function and histology were indistinguishable from those
      of conventional liver transplantation. Ascites disappeared within 3-4 months and
      the patients were able to return to their normal activities. Postoperative
      variceal bleeding necessitated splenectomy and gastric devascularization in one
      case and splenic artery embolization in another case. Bleeding was controlled in
      both these cases. Splenectomy and gastric devascularization were performed
      prophylactically in one patient with a history of variceal bleeding in order to
      prevent this complication after transplantation. CONCLUSION: Portocaval
      hemitransposition maybe useful in liver transplantation when hepatopetal flow to
      the liver graft cannot be established by other techniques. Rescue after failure
      of conventional technique was not possible in two patients.

PMID- 9521195
TI  - Cold preservation of isolated rabbit proximal tubules induces radical-mediated
      cell injury.
AB  - BACKGROUND: Reactive oxygen species (ROS) are involved in reperfusion injury
      after preservation. Recent studies in isolated endothelial cells and hepatocytes
      suggested the occurrence of ROS-mediated injury during the period of cold
      incubation. In the present study, formation of ROS and subsequent cell injury
      were studied in freshly isolated rabbit proximal tubules (PTs). METHODS: PTs were
      incubated in University of Wisconsin (UW) solution, Euro-Collins solution, or a
      modified Krebs-Henseleit buffer under aerobic conditions for up to 94 hr at 4
      degrees C. ROS formation and cell death were assessed as lipid peroxidation
      (formation of thiobarbituric acid-reactive substances [TBARS]) and release of
      lactate dehydrogenase, respectively. The involvement of ROS was further
      investigated in UW solution using compounds that might interfere with ROS
      formation. In addition, tubules were studied under anaerobic conditions (gassing
      with 95% N2/5% CO2). RESULTS: Cold preservation of rabbit PTs in any of the
      solutions under aerobic conditions caused progressive lipid peroxidation and
      concomitant cell injury. Addition to UW solution of inhibitors of ROS formation,
      in particular 2,2'-dipyridyl, or removal of oxygen by gassing with 95% N2/5% CO2,
      prevented lipid peroxidation and protected rabbit PTs against cold injury. Both
      the nitric oxide (NO) synthase inhibitor L-NAME and dexamethasone, which blocks
      the inducible NO synthase, were ineffective. The cytoprotectant glycine affected
      neither TBARS formation nor lactate dehydrogenase release. CONCLUSIONS: Cold
      preservation of renal PTs under aerobic conditions caused cell injury even in the
      specially designed preservation solution UW. Cell injury is caused by iron
      dependent, NO synthase-independent ROS formation.

PMID- 9521196
TI  - Humanized IgG1 and IgG4 anti-CD4 monoclonal antibodies: effects on lymphocytes in
      the blood, lymph nodes, and renal allografts in cynomolgus monkeys.
AB  - BACKGROUND: Optimizing therapeutic monoclonal antibody (mAb) depends on the
      incorporation of the necessary effector functions and the development of
      hypoantigenic "humanized" antibodies by genetic engineering, which then need to
      be tested in appropriate preclinical trials. METHODS: Constructs of humanized
      OKT4A containing the complementarity-determining region (CDR) of murine OKT4A and
      the framework and constant regions of human light (kappa) and heavy chains (IgG1
      and IgG4) were prepared and tested in cynomolgus monkeys who received a renal
      allograft. A prophylactic course of CDR-OKT4A/human (h) IgG1 or CDR-OKT4A/ hIgG4,
      either as high-dose single bolus (10 mg/kg) or as low-dose multiple infusion (1
      mg/kg for 12 days) was given, and the effects on graft survival, immunohistology,
      circulating cells, and lymph node cells were assessed. RESULTS: The IgG1 isotype
      induced coating of T cells, modulation of surface CD4 molecules, and profound
      depletion of CD4+ lymphocytes in peripheral blood, which persisted as long as the
      animals were followed (up to 7 weeks). The IgG4 isotype induced only cell coating
      without cell clearance or modulation. In lymph nodes, coating of lymphocytes
      (approximately 60%) was seen with both isotypes in the earliest sample (6 hr).
      After 2 days, significant depletion of lymph node CD4 cells was evident, with a
      decrease in the CD4 to CD8 ratio in the IgG1-treated group; no depletion occurred
      in the IgG4 group. The emigration of CD4+ cells into the allograft was
      significantly delayed in the CDR-OKT4A/hIgG1-treated animals when compared with
      the CDR-OKT4A/hIgG4 group as judged by immunocytochemistry (23.8+/-13.2 days vs.
      7.4+/-1.5 days, P<0.001) or interleukin-2-promoted T-cell outgrowth from
      allograft biopsies (22.2+/-11.0 days vs. 6.3+/-0.5 days, P<0.01). CONCLUSIONS:
      This study demonstrates that the in vivo effects of CDR-grafted OKT4A are
      dependent on its isotype. The depleting mAb CDR-OKT4A/hIgG1 significantly delays
      the entry of CD4+ cells into the graft, inhibiting the early phase of rejection.
      However, graft rejection occurs when CD4+ cells eventually infiltrate the graft,
      even in the presence of depressed levels of circulating CD4+ cells. Both isotypes
      demonstrated therapeutic efficacy: graft survival was prolonged over controls. In
      the case of CDR-OKT4A/hIgG4, neither lymphocyte depletion, antigenic modulation,
      nor prevention of infiltration is necessary for a beneficial effect, which
      indicates that this mAb blocks CD4 function or renders the CD4+ cell less
      responsive. The lack of depletion is a feature of potential clinical advantage in
      minimizing the risk of excessive immunosuppression.

PMID- 9521197
TI  - Cytomegalovirus prophylaxis with antiviral agents in solid organ transplantation:
      a meta-analysis.
AB  - BACKGROUND: The aim of this meta-analysis was to assess the efficacy of antiviral
      agents to prevent, in solid organ transplant recipients, cytomegalovirus
      infection and symptomatic disease and to decrease the incidence of acute
      rejection, graft loss, and death. METHODS: Of the studies identified, 13 met the
      following inclusion criteria: prospective randomized study, in adults or
      pediatric recipients of a solid organ transplant, where one group in the study
      received a prophylactic treatment with acyclovir and/or ganciclovir begun before
      the cytomegalovirus infection and a control group was not treated or receive
      placebo. RESULTS: Prophylactic treatment was found to be associated with a
      significant decrease of cytomegalovirus disease compared with placebo or no
      treatment, using the logarithm of relative risk method (relative risk=0.50; 95%
      confidence interval, 0.40-0.62; P-value for chi-square association <0.001).
      Prophylactic treatment decreased also the rate of cytomegalovirus infection
      (relative risk=0.74; 95% confidence interval, 0.62-0.88; P<0.001). Our analysis
      failed to show a significant decrease of graft loss, acute rejection, and death
      in the prophylactic treatment group. Subgroup analysis based on the type of
      antiviral agent (acyclovir or ganciclovir) and on the type of organ (kidney or
      liver) gave comparable results. CONCLUSION: The use of antiviral agents for the
      prevention of cytomegalovirus disease and cytomegalovirus infection in solid
      organ transplantation is supported by this meta-analysis.

PMID- 9521198
TI  - HLA-A locus mismatches and development of antibodies to HLA after lung
      transplantation correlate with the development of bronchiolitis obliterans
      syndrome.
AB  - BACKGROUND: Bronchiolitis obliterans syndrome (BOS) is the most common cause of
      morbidity and mortality after lung transplantation (LT). A retrospective analysis
      of clinical and immunologic variables were done to identify those that might
      predict the development of BOS. METHODS: Of 112 LT performed over a 42-month
      interval, 94 survived at least 3 months and form the basis of this analysis.
      There was a minimum of 21 months follow-up. BOS was defined on the basis of
      declining spirometry (FEV1 <80% of baseline) and/or the presence of histologic
      obliterative bronchiolitis. All variables analyzed were subjected first to a
      univariate analysis; those variables appearing to carry significance were then
      subjected to a multivariate logistic regression analysis. RESULTS: Univariate
      analysis revealed the following to be predictors of the development of BOS: age
      (the probability of developing BOS declined with advancing age); donor/recipient
      HLA-A locus mismatch, with actuarial freedom from BOS being significantly greater
      with no A-locus mismatches versus cases with one or two mismatches (P=0.031); and
      development of anti-HLA antibodies after transplantation (P=0.006 vs. recipients
      without detectable antibodies). In multivariate analysis, only HLA locus mismatch
      and development of anti-HLA antibodies were significant independent predictors of
      the development of BOS. The remaining clinical variables (gender, type of LT,
      indication for LT, graft ischemic time, use of cardiopulmonary bypass,
      cytomegalovirus) and immunologic variables (crossmatch, frequent early acute
      rejection) did not correlate with the development of BOS. CONCLUSIONS: These data
      suggest that BOS is the result of an immune process, that differences at the HLA
      A locus may play an important role in this process, and antibody-mediated injury
      may play a role in BOS.

PMID- 9521199
TI  - A randomized trial comparing cyclosporine and steroids with cyclosporine,
      azathioprine, and steroids in cadaveric renal transplantation.
AB  - BACKGROUND: In renal transplantation, triple-drug therapy (low-dose cyclosporine
      [CsA] combined with azathioprine plus steroids) has been replacing double-drug
      therapy (CsA plus steroids) in clinical practice without much evidence in favor
      of either therapy. Previous trials comparing the two immunosuppressive regimens
      gave conflicting results. We attempted to determine whether triple therapy is at
      least equivalent to double therapy. METHODS: A randomized trial was performed in
      250 adult cadaveric renal transplant recipients, comparing double therapy (CsA
      [10 mg/kg/day] plus prednisone) with triple therapy (CsA [6 mg/kg/day] plus
      azathioprine plus prednisone). The median follow-up time was 930 days. RESULTS:
      The incidence of acute rejection episodes refractory to treatment was 11% in
      double therapy and 4% in triple therapy (relative risk reduction: 64%; 95%
      confidence interval: 5-100%; P=0.035). Patients in the double therapy group
      required more intensive antirejection treatment, and their pathologic lesions
      were more severe. The proportion of patients with acute rejection was similar
      (double therapy: 45% vs. triple therapy: 40%) as was the incidence of chronic
      renal dysfunction (double therapy: 17% vs. triple therapy: 15.5%), the 4-year
      graft survival (double therapy: 71% vs. triple therapy: 83%, P=0.089), and
      patient survival (double therapy: 94% vs. triple therapy: 93%). In 29 patients
      (23%), 35 episodes of azathioprine-induced leukopenia were recorded, and in 9 of
      them azathioprine had to be discontinued. The incidence of other adverse events
      did not differ between the groups. CONCLUSIONS: Triple therapy caused fewer
      episodes of refractory acute rejection episodes and was as efficacious and safe
      as double therapy.

PMID- 9521200
TI  - Long-term improvement in renal function after cyclosporine reduction in renal
      transplant recipients with histologically proven chronic cyclosporine
      nephropathy.
AB  - BACKGROUND: Chronic cyclosporine (CsA) nephropathy, which has been unequivocally
      documented in recipients of heart, heart-lung, liver, or bone marrow transplants,
      as well as in nontransplant situations, usually results in a progressive
      deterioration of renal function. In this study, we assessed the potential
      reversibility of chronic CsA nephropathy in renal transplant recipients. PATIENTS
      AND METHODS: Twenty-three renal transplant patients with biopsy-proven CsA
      nephropathy associated with long-term CsA administration (27+/-4 months) were
      followed up for more than 2 years after CsA reduction (18/23 patients) or
      withdrawal (5/23 patients) and addition of azathioprine. Changes in effective
      renal plasma flow and glomerular filtration rate were assessed before and 2 years
      after CsA reduction, whereas serum creatinine, proteinuria, blood pressure, and
      CsA concentrations were monitored up to 5 years. RESULTS: At 2-year follow-up,
      glomerular filtration rate increased from 40+/-3 to 47+/-4 (P<0.05) and effective
      renal plasma flow from 217+/-23 to 244+/-24 ml/min/1.73 m2 (NS). Mean arterial
      pressure significantly decreased from 98.7+/-2.9 to 93.1+/-2.7 mmHg (P<0.05).
      There was no significant change in renal vascular resistance, filtration
      fraction, or albumin excretion. A significant decrease in serum creatinine was
      also observed during the whole follow-up (73+/-6.5 months). CsA reduction was
      followed by only one episode of acute reversible rejection; chronic rejection
      developed in three patients 2 years or later after CsA reduction. CONCLUSIONS:
      These data suggest that CsA nephropathy participates in graft dysfunction in a
      small group of renal transplant recipients. In addition, graft dysfunction may be
      reversible when CsA dosage is reduced early after diagnosis of chronic CsA
      nephropathy.

PMID- 9521201
TI  - Harmful long-term impact of hepatitis C virus infection in kidney transplant
      recipients.
AB  - BACKGROUND: The long-term impact of hepatitis C virus (HCV) infection in renal
      transplant recipients remains controversial. We report here our experience, in a
      homogeneous single center, of 499 patients with a fairly long follow-up. METHODS:
      We retrospectively studied 499 hepatitis B virus-negative patients who received
      an initial cadaver donor kidney transplantation at Necker Hospital between
      January 1, 1979 and December 31, 1994, with a graft or patient survival of at
      least 6 months. Anti-HCV antibodies were detected at time of transplantation in
      112 patients (22%). Patient survival and causes of death were compared among anti
      HCV-positive and -negative patients RESULTS: Our results clearly indicate that
      first cadaver kidney transplant recipients with anti-HCV antibodies had a
      significantly shorter patient and graft long-term survival than recipients
      without anti-HCV antibodies (P<0.01 and P<0.0001 respectively). Mean follow-up
      time after transplantation was 79+/-2 months in the former group and 81+/-5
      months in the latter (NS). Increased mortality was primarily caused by liver
      disease (P<0.001) and sepsis (P<0.01). In a multivariate analysis, HCV infection
      significantly affected the mortality rate (odds ratio: 2.8). CONCLUSIONS: These
      results suggest that HCV infection has a harmful long-term impact on the survival
      of kidney transplant recipients.

PMID- 9521202
TI  - Recipient body surface area as a predictor of posttransplant renal allograft
      evolution.
AB  - BACKGROUND: The aim of the present study was to analyze whether minor differences
      in recipient body surface area have any predictive value on renal allograft
      evolution. METHODS: For this study, we considered 236 pairs of recipients who
      received a kidney from the same donor at our center between March 1985 and
      December 1995. Pairs in whom at least one patient presented any of the following
      events were excluded: graft loss during the first year of follow-up, diabetes
      mellitus, noncompliance with treatment, chronic pyelonephritis, and recurrent or
      de novo glomerulonephritis. Recipients of each pair were classified as large or
      small according to their body surface area (BSA). The percentage difference of
      BSA in each pair was calculated, and two cohorts of pairs were defined: BSA
      difference < or = 10% (n=76 pairs) and BSA difference >10% (n=70 pairs). RESULTS:
      The large recipients of the cohort with a BSA difference >10% showed a higher
      incidence of posttransplant delayed graft function (22/70 vs. 12/70, P=0.075),
      hypertension at 1 year of follow-up (51/70 vs. 35/70, P=0.006), and a higher
      serum creatinine level at 1-year follow-up (173 vs. 142 micromol/L, P=0.003),
      whereas in the cohort with a BSA difference < or = 10%, posttransplant evolution
      in large and small recipients was not different. Multivariate analysis showed
      that recipient BSA was an independent predictor of delayed graft function,
      posttransplant hypertension, and serum creatinine at 1-year follow-up.
      CONCLUSIONS: Relatively small differences in recipient BSA influence renal
      allograft evolution. Consequently, our data support that recipient size should be
      taken into consideration for renal allograft allocation.

PMID- 9521203
TI  - Early hepatocyte, endothelial, and bile duct cell injury after pediatric liver
      transplantation from cadaveric or living-related donors.
AB  - BACKGROUND: When compared with cadaveric grafts (Cad), the potential advantages
      of pediatric orthotopic liver transplantation (OLT) from living-related (LR)
      donors may include better graft quality, shorter ischemic time, appropriate
      preparation of the recipient, and better immunologic compatibility. METHODS: The
      aim of this study was to analyze early hepatocyte, endothelial, and bile duct
      cell injury following pediatric OLT using LR (n=15) or uncomplicated Cad reduced
      size (n=10) grafts. Median (range) total ischemic times were 190 min (105-261)
      versus 760 min (418-948) in LR and Cad groups, respectively (P<0.001). RESULTS:
      The post-OLT cytolytic profile, assessed daily during the first 7 days using both
      plasma glutamate-pyruvate transaminase and serum alpha-glutathione S-transferase,
      showed significantly higher levels of both parameters for the 10 uncomplicated
      Cad cases when compared with the 15 LR grafts (P<0.001). The evaluation of
      hepatic endothelial cell function during the first week after OLT, using serum
      hyaluronic acid levels, suggested lower endothelial injury in the LR grafts, when
      compared with the Cad grafts (P=0.059). Bile duct cell injury, as assessed using
      plasma gamma-glutamyl transferase levels, was similar in both groups, with a
      progressive increase at the end of the first week after OLT, which was correlated
      with a similar incidence of early acute rejection in both groups (80% in the LR
      group vs. 62% in the Cad group, NS). CONCLUSION: (1) The hepatocellular and
      endothelial cell damage was reduced after OLT with LR grafts, which may be
      related to shorter ischemic time when compared with Cad grafts; (2) the putative
      immunologic advantage for LR grafts was not confirmed in terms of incidence of
      acute rejection.

PMID- 9521204
TI  - Living-related liver transplantation and neurological outcome in children with
      fulminant hepatic failure.
AB  - BACKGROUND: Fulminant hepatic failure (FHF) in children is associated with high
      mortality under medical management. Living-related liver transplantation (LRLT)
      is an accepted measure to treat the children with end-stage liver disease.
      Reversibility of hepatic encephalopathy is crucial for the quality of life among
      the survivors after transplantation. METHODS: A retrospective review was made of
      the records of children undergoing LRLT at this hospital between May 1992 and
      November 1996. RESULTS: Eleven children with FHF underwent emergency LRLT. The
      mean age was 5 years (range, 2 months to 15 years). The indication for
      transplantation was persistent or worsening hepatic encephalopathy and severe
      coagulopathy, despite repeated plasma exchanges or exchange transfusions. The
      cause of FHF was non-A, non-B hepatitis in seven children, hepatitis B in two
      children, herpes simplex virus hepatitis in one child, and fulminant Wilson's
      disease with intravascular hemolysis in one child. The grade of hepatic
      encephalopathy was II in four children, III in two, and IV in five. The actuarial
      survival rate was 73% after a mean follow-up of 28 months (range, 13-67 months).
      Short-term neurological morbidity was present in two children with grade IV
      encephalopathy who also showed brain edema on cranial computed tomography. Eight
      survivors exhibited no long-term neurological deficit; the mean intelligence or
      developmental quotient was 97 (range, 86-110) at the end of the follow-up period.
      CONCLUSIONS: LRLT is an effective option for the treatment of FHF in children.
      The long-term neurological status is satisfactory among survivors.

PMID- 9521205
TI  - Prognostic implications of centrilobular necrosis in pediatric liver transplant
      recipients.
AB  - BACKGROUND: We have observed centrilobular necrosis (CLN) in several liver
      allograft biopsies in our pediatric liver transplant population. The aims of this
      study were to describe the associated pathologic and clinical features of post
      orthotopic liver transplantation CLN and determine its prognostic implications.
      METHODS AND RESULTS: CLN was identified and characterized in 44 allografts from
      40 patients (17 males and 23 females) among our 443 pediatric recipients. Twenty
      episodes were associated with cellular rejection, either in the same biopsy
      (n=15) or within the week prior (n=5), and five were associated with ductopenic
      rejection. Twelve were associated with vascular thrombosis. No clear etiology was
      identified in seven episodes, but two also had cholangitis lenta. Of the
      remaining five biopsies, three showed only centrilobular dropout, suggesting a
      resolution of some previous insult. The outcome of 40 patients following an
      initial episode of CLN was poor, with graft failure in 33, chronic poor function
      in 2, and normal recovery in only 5 patients. The results of retransplantation
      for graft failure due to CLN were equally poor, with 14 deaths, 3 patients with
      ductopenic rejection, and only 5 with normal recovery. CLN recurred in four
      grafts. Overall patient outcome was very poor: 25 deaths; 3 ductopenic
      rejections; 2 chronic poorly functioning livers; and 10 patients alive and well.
      CONCLUSION: We conclude that CLN in pediatric orthotopic liver transplantation
      recipients is associated with cellular rejection, ductopenic rejection, or acute
      vessel thrombosis in the majority cases. The prognostic implications of CLN are
      grave, with high rates of graft failure requiring retransplantation and death.

PMID- 9521206
TI  - Blockade of very late antigen-4 integrin binding to fibronectin in allograft
      recipients: I. Treatment with connecting segment-1 peptides prevents acute
      rejection by suppressing intragraft mononuclear cell accumulation, endothelial
      activation, and cytokine expression.
AB  - BACKGROUND: Allograft rejection is associated with infiltration of inflammatory
      cells and local deposition of fibronectin (FN). This study was carried out to
      examine the hypothesis that peptides known to specifically block adhesive
      interactions between the connecting segment-1 (CS1)-binding domain of FN and
      alpha4beta1 integrin on circulating cells may interfere with the immune cascade,
      which would lead to acute rejection in transplant recipients. METHODS AND
      RESULTS: Cardiac allografts from Lewis x Brown Norway F1 hybrids were rejected in
      7+/-1 days in Lewis rats. Treatment with bioactive CS1 peptides (4 mg/kg/day i.v.
      for 7 days) abrogated acute rejection and prolonged cardiac allograft survival to
      13+/-1 days (P<0.001). This effect correlated with decreased expression of total
      fibronectin and cell adhesion molecules, such as alpha4beta1, vascular cell
      adhesion molecule-1, intercellular adhesion molecule-1, as well as reduced
      infiltration by CD4+ and CD8+ T cells at the graft site. Treatment with CS1
      peptides decreased alloantigen activation, as evidenced by decreased intragraft
      infiltration by CD25+ cells, and diminished expression of mRNA coding for Th1
      (interleukin [IL]-2, interferon-gamma)- and Th2 (IL-4, IL-5, IL-6)-type
      cytokines. CS1-mediated immunosuppressive effects could be reversed and acute
      rejection recreated after adjunctive treatment of rats with recombinant IL-2.
      CONCLUSION: Our data are consistent with the model in which in vivo interaction
      between the alpha4beta1 integrin receptor and the cell-associated CS1 motif of FN
      is critical for rejection cascade. The novel therapeutic approach of selectively
      blocking the alpha4beta1-FN activation pathway with CS1 peptides prevents acute
      allograft rejection by inhibiting expansion of antigen-specific T cells and
      inducing a transient state of cytokine-responsive anergy in the residual T-cell
      population.

PMID- 9521207
TI  - Indirect recognition of porcine xenoantigens by human CD4+ T cell clones.
AB  - BACKGROUND: Human T-cell response against xenogeneic antigens may occur either by
      direct recognition of antigens on xenogeneic antigen-presenting cells (APCs) or
      by an indirect pathway mediated by autologous APCs. METHODS: The proliferative
      response of human CD4+ T cells to porcine aortic endothelial cells (PAECs) was
      measured. From these T-cell lines, eight CD4+ T-cell clones were obtained by
      limiting dilution. RESULTS: CD4+ T cells, in the absence of monocytes,
      proliferated in response to PAECs only after swine leukocyte antigen (SLA) class
      II molecules were induced on PAECs. The proliferation was significantly better
      when autologous human monocytes were added back as APCs. All of the eight CD4+ T
      cell clones demonstrated specific proliferative response when stimulator PAECs,
      but not PAECs of other porcine origins, were preincubated with autologous human
      APCs before addition of these clones. These results indicated that the clones are
      recognizing porcine xenoantigens presented by self-APCs. The proliferative
      response of CD4+ T-cell clones was blocked by antibodies directed against human
      leukocyte antigen class II and human CD4, but not by anti-SLA class II monoclonal
      antibodies. A marked inhibition in proliferation was also noted when human APCs
      were incubated with chloroquine before addition to the cultures, indicating that
      xenoantigens had to be processed in order to be recognized by the clones.
      CONCLUSIONS: Human CD4+ T cells can recognize xenoantigens by either a direct or
      indirect pathway. The CD4+ T-cell clones developed against SLA class II-negative
      PAECs recognized strain-specific porcine xenoantigens indirectly.

PMID- 9521208
TI  - Human hepatocytes produce an isoform of FAS that inhibits apoptosis.
AB  - BACKGROUND: Fas (Apo-1/CD95), a member of the tumor necrosis factor receptor
      family, can mediate apoptosis when engaged by its ligand or by anti-Fas antibody.
      Fas is expressed by cells of the immune system and by some nonlymphoid tissues.
      Numerous studies have suggested that the Fas pathway may play a role in the
      rejection of allografts. Functional, soluble forms of the Fas receptor are
      produced by activated peripheral blood mononuclear cells and some transformed
      cell lines. The purpose of this study was to determine if soluble variants of Fas
      are produced in the liver and to determine if blockade of the Fas pathway, by
      liver-derived soluble Fas, inhibits Fas-mediated apoptosis. METHODS: Liver and
      purified hepatocyte specimens were analyzed for Fas transcripts by reverse
      transcriptase-polymerase chain reaction with primers that span the transmembrane
      region of the molecule. Bile and cell lysates were analyzed for soluble Fas by
      specific enzyme-linked immunosorbent assay. Lysates were prepared from normal
      liver and hepatocytes and utilized to block Fas-mediated apoptosis of Jurkat
      cells as determined by terminal deoxynucleotidyl transferase-mediated dUTP nick
      end labeling and flow cytometry. RESULTS: A variant form of Fas is abundantly
      expressed in normal liver and purified hepatocytes. This variant form of Fas is
      expressed in all normal liver specimens but only in half of the liver specimens
      obtained during allograft rejection. The levels of soluble Fas diminish in
      patients undergoing liver allograft rejection in contrast to patients with stable
      grafts. Importantly, a soluble form of Fas is produced in the liver by
      hepatocytes and can specifically inhibit Fas-mediated apoptosis. CONCLUSION:
      These data raise the possibility that soluble Fas, produced by hepatocytes, may
      influence the immune response by blocking Fas-mediated apoptosis and, thus, may
      have a role in liver transplantation.

PMID- 9521209
TI  - Endotoxin contamination may be responsible for the unexplained failure of human
      pancreatic islet transplantation.
AB  - Clinical transplantation of human islets has a disappointingly low rate of
      success. We report here the identification of a possible causative factor:
      endotoxin present in the collagenase preparations used to disperse the pancreatic
      tissue before islet purification and transplantation. Supporting evidence
      includes (1) detection of unexpectedly high levels of endotoxin in most
      collagenase solutions currently used to digest human pancreases; (2)
      demonstration that supernatants generated during islet separation are able to
      induce the inflammatory cytokines interleukin (IL)-1, IL-6, and tumor necrosis
      factor-alpha (TNF-alpha) in macrophages; and (3) induction of IL-1, IL-6, and TNF
      alpha in the islets during the separation procedure. Cytokine expression was
      assessed by reverse transcription-polymerase chain reaction and, for TNF-alpha,
      confirmed by enzyme-linked immunoabsorbent assay. It is proposed that endotoxin
      and locally induced cytokines carried over with the graft activate the
      endothelium and promote lymphomonocytic infiltration of grafted islets and
      surrounding liver tissue favoring primary nonfunction and early rejection. These
      results also have implications for the numerous experimental procedures that use
      collagenase, and they point to possible ways to improve islet preparation and
      transplantation protocols.

PMID- 9521210
TI  - Importance of natural killer cells in the rejection of hamster skin xenografts.
AB  - BACKGROUND: In the hamster to rat xenogeneic combination, antibodies, T cells,
      and natural killer (NK) cells have all been implicated in the process of
      rejection. 3.2.3 is a mouse IgG1kappa monoclonal antibody (mAb) directed against
      NKR-P1A on rat NK cells. The purpose of this study was to evaluate the effect of
      this mAb independently and in combination with other immunosuppressive agents in
      a hamster to rat skin graft model in order to elucidate the mechanisms involved
      in xenograft rejection. METHODS: Lewis rats were recipients of hamster skin
      grafts. Various groups received antilymphocyte serum (ALS) (days -1, 0, and +2),
      rapamycin (3 mg/kg; alternate days from day +1 through day +13), and 3.2.3 mAb
      (days 0, +1, and +2). Anti-hamster antibody production was determined serially
      with a complement-dependent cytotoxicity assay. Lewis anti-hamster mixed
      lymphocyte reaction and cell-mediated lympholysis assays were performed within 7
      days after rejection of the skin graft. NK cell function was tested using a
      cytotoxicity assay versus YAC-1 target cells on day 14 or day 15 after skin
      grafting. RESULTS: Median graft survival in untreated animals was 7 days. There
      was only modest prolongation in rats treated with rapamycin alone (median
      survival time [MST]=9 days) or ALS alone (MST=10 days). The use of 3.2.3 mAb in
      untreated rats (3.2.3 alone MST=7 days) and in ALS-treated rats (ALS+3.2.3
      MST=9.5 days) did not improve graft survival. The combination of ALS+rapamycin
      substantially improved graft survival (MST=13 days), and even greater
      prolongation was seen with the addition of 3.2.3 mAb (ALS+rapamycin+3.2.3
      MST=18.5 days). Cytotoxic antibodies, secondary mixed lymphocyte reaction
      responses, cytotoxic T cells, and normal NK activity were seen at the time of
      rejection in untreated rats as well as those treated with 3.2.3 mAb alone, ALS
      alone, ALS+3.2.3 mAb, and rapamycin alone. ALS+rapamycin completely blocked the
      formation of anti-hamster antibodies and cytotoxic T cells but did not suppress
      NK activity. The use of 3.2.3 mAb produced a marked but transient suppression of
      NK activity in all groups. CONCLUSION: Hamster skin xenografts can be rejected by
      Lewis rats in the absence of cytotoxic antibodies and cytotoxic T cells. ALS,
      rapamycin, and ALS+rapamycin do not suppress NK activity in Lewis rats, although
      their use produces a modest prolongation of hamster skin graft survival. The
      administration of 3.2.3 mAb to Lewis rats results in a marked but transient
      suppression of NK cell function, which substantially prolongs hamster skin graft
      survival only when antibody and cytotoxic T-cell production have also been
      suppressed.

PMID- 9521212
TI  - Impact of immunoadsorption on complement activation, immunopathology, and hepatic
      perfusion during xenogeneic pig liver perfusion.
AB  - BACKGROUND: The impact of antibody adsorption by immunoapheresis on liver damage,
      complement activation, and hepatic perfusion was evaluated against the background
      of an application in extracorporeal pig liver perfusion for hepatic coma.
      METHODS: Eighteen pig livers were ex vivo perfused close to physiological
      conditions with fresh human blood for 4 hr. The influence of the perfusion
      circuit was investigated by perfusions of the circuit in the absence of livers
      (group 1 [G1]; n=5). Livers were xenoperfused without modifications in group 2
      (G2; n=6). In group 3 (G3; n=6), pure Sepharose columns were used prior to liver
      perfusion. Immunoapheresis with Ig-Therasorb 100 columns was used in group 4 (G4;
      n=6). RESULTS: IgG was reduced by 95%, IgM by 72%, and IgA by 82% in G4, but only
      by about 30% in G3 (P<0.05). C4d, Bb fragment, and C3a levels were significantly
      lower in G4 than in G3 and G2 (P<0.05) after 180 min. Immunoadsorption diminished
      antibody and complement deposition as well as hepatocellular damage in G4. Portal
      angiographies demonstrated improved hepatic perfusion in G4. CONCLUSION:
      Immunoapheresis reduced organ damage as well as complement activation and
      improved hepatic perfusion during xenogeneic pig liver perfusion.

PMID- 9521211
TI  - Deuterium oxide-based University of Wisconsin solution improves viability of
      hypothermically stored vascular tissue.
AB  - BACKGROUND: Preservation of vascular function largely determines the outcome of
      transplantation. We have investigated replacing the water (H2O) in University of
      Wisconsin (UW) solution with deuterium oxide (D2O) in an attempt to improve
      vascular function after hypothermic storage. METHODS: Rat aortic segments were
      stored in UW solutions based on 100% H2O, 25% D2O, 50% D2O, and 100% D2O at 4
      degrees C for 24, 48, or 72 hr. Vascular function was measured via contraction
      and endothelium-dependent relaxation after stimulation with phenylephrine and
      acetylcholine. RESULTS: UW solution with 25% D2O gave a significant (P<0.05)
      improvement of contraction and relaxation in comparison with H2O-based UW
      solution and other concentrations of D2O. CONCLUSIONS: Low concentrations (25%)
      of D2O-UW solution are significantly superior to the H2O-based (i.e., commonly
      used) equivalent at up to 72 hr. These results suggest that low concentrations of
      D2O-UW solution can improve the quality of hypothermic storage.

PMID- 9521213
TI  - Pretransplant hepatitis C virus infection: a predictor of proteinuria after renal
      transplantation.
AB  - BACKGROUND: Reports have suggested that hepatitis C virus (HCV)-infected kidney
      recipients may develop de novo glomerular lesions caused by the virus. We studied
      the relationships between pretransplantation anti-HCV antibodies and the
      occurrence of proteinuria and the link with short- and long-term patient and
      graft survival. METHODS: A total of 322 consecutive renal recipients treated at a
      single center from 1989 to 1994 whose sera were routinely assayed for anti-HCV
      antibodies at the time of transplantation were analyzed. The risks of persistent
      proteinuria (>1 g/day), graft loss, or death were estimated by Kaplan-Meier
      analysis. The relationship between clinical variables and each outcome was
      examined by Cox multivariate regression analysis. RESULTS: Before
      transplantation, 9.6% of the recipients were anti-HCV antibody positive.
      Persistent proteinuria developed in 13.6% recipients. The presence of anti-HCV
      antibodies was strongly associated with proteinuria (relative risk [RR]=5.36, 95%
      confidence interval [CI]=2.49-11.51). Proteinuria occurred more frequently in
      second grafts (RR=2.64, 95% CI=1.10-6.29). The number of HLA-A,B mismatches was
      an independent risk factor (RR=1.55, 95% CI=1.10-2.19). Recipient age (RR=0.80,
      95% CI=0.63-1.02) and duration of dialysis (RR=0.86, 95% CI=0.77-0.96) were
      protective factors. Histology of biopsies from 26/44 recipients with proteinuria
      showed that de novo glomerular lesions were more frequent in HCV-positive
      patients, although the difference was not significant. One- and five-year graft
      survival rates were significantly worse in patients with proteinuria (90.7% and
      41.1%) than in patients without it (95.6% and 91.8%) (P<0.00001). Despite the
      strong association between HCV infection and proteinuria, patient and graft
      survival rates in anti-HCV-positive and anti-HCV-negative recipients were
      similar. CONCLUSIONS: The presence of anti-HCV antibodies before renal
      transplantation seems to be a major risk factor of proteinuria after
      transplantation. This may be due to glomerular lesions caused by HCV. However,
      anti-HCV has no impact on 5-year patient and graft survival.

PMID- 9521214
TI  - Impotence and the use of the internal iliac artery in renal transplantation: a
      survey of surgeons' attitudes in the United Kingdom and Ireland.
AB  - BACKGROUND: In 1996, a court in the United Kingdom ruled against a plaintiff who
      claimed that: (1) division of both internal iliac arteries at separate renal
      transplant operations had made him impotent and (2) the risk of his becoming
      impotent was sufficiently high that he should have been warned. The court ruled
      that there was not enough evidence in the medical literature to allow his claim
      to succeed. METHODS: A survey of the views of transplant surgeons in the United
      Kingdom and Ireland on attitudes toward using the internal iliac artery for
      transplantation was conducted. RESULTS: A 100% response rate was received. In a
      potent male patient, 11% of surgeons would never use the first internal iliac
      artery and 52% would use it infrequently. If one internal iliac artery had
      already been used, 61% would never use a second and 34% would use it
      infrequently. Eighty-nine percent believed the risk of impotence when the second
      internal iliac artery was used was 25% or higher, and 91% thought the risk should
      be explained to the patient. CONCLUSION: A very strong opinion exists among
      transplant surgeons in the United Kingdom and Ireland that the second internal
      iliac artery should not be used to revascularize a kidney transplant when the
      first has already been divided. The risk of impotence, if the second internal
      iliac artery is used, is greater than 25% and should be explained to the patient.
      This represents a very clear statement of currently accepted practice.

PMID- 9521215
TI  - Preemptive treatment for the prevention of cytomegalovirus disease: in lung and
      heart transplant recipients.
AB  - BACKGROUND: Rapid quantifiable diagnostic techniques for the diagnosis of
      cytomegalovirus (CMV) infection may predict patients at risk of CMV pneumonitis
      and allow preemptive antiviral treatment. METHODS: Using CMV antigenemia as a
      prospective surveillance technique for CMV infection, we compared the outcome of
      preemptive treatment (PT) with ganciclovir, 10 mg/kg/day for 21 days directed by
      "high levels" of CMV antigenemia (PT group, n= 19), with the outcome in a group
      of historical controls (n=18) treated with ganciclovir when CMV illness occurred.
      Greater than 50 antigen-positive cells per 2 x 10(5) polymorphonuclear leukocytes
      was considered to be high-level antigenemia. RESULTS: Nine of the 18 controls
      developed high-level CMV antigenemia at a median of 33 days (range: 13-65 days)
      and 5 of the 9 developed CMV disease. Ten of the 19 PT group had high levels of
      CMV antigenemia detected at a median of 47 days (range: 20-63 days) and were
      given ganciclovir; none developed CMV disease. There was a significantly lower
      incidence of CMV disease in the PT group in comparison to controls (0 of 19 vs. 5
      of 18: P=0.019). CONCLUSION: We have reduced the incidence of CMV disease using
      preemptive treatment, and because of a 100% negative predictive value, we omitted
      unnecessary antiviral prophylaxis for many at-risk patients.

PMID- 9521216
TI  - Peaks of transforming growth factor-beta mRNA in alveolar cells of lung
      transplant recipients as an early marker of chronic rejection.
AB  - BACKGROUND: Chronic lung rejection (CLR) induces a fibroproliferative disorder
      leading to the occlusion of small airways. It has emerged as the major factor
      limiting the survival of lung transplant recipients. Predictive markers of CLR
      are lacking, and its diagnosis is generally ascertained when the fibrosis process
      is irreversible. METHODS: We have quantified the expression of transforming
      growth factor-beta (TGF-beta), a critical mediator of fibrogenesis, in alveolar
      cells from lung transplant recipients using a competitive reverse transcriptase
      polymerase chain reaction method. RESULTS: We have shown that patients with CLR
      presented marked peaks of TGF-beta mRNA expression, in contrast with patients
      without CLR. These peaks preceded the diagnosis of CLR by several months in two
      of three patients who died within 2 years of diagnosis. CONCLUSIONS: Our data
      suggest that TGF-beta expression in alveolar cells could serve as an early
      predictive and prognostic marker of chronic lung rejection.

PMID- 9521217
TI  - Effect of verapamil on lymphocyte infiltration.

PMID- 9521218
TI  - Humoral alloreactivity in recipients of renal allografts as a risk factor for the
      development of delayed graft function.

PMID- 9521219
TI  - Dose-dependent reduction of bile secretion in cyclosporine-treated rats.

PMID- 9521220
TI  - Multiple sclerosis: what have we learned from magnetic resonance imaging studies?
AB  - We review studies that have examined the relationship between magnetic resonance
      imaging findings and clinical disability, postmortem observations, and cognitive
      dysfunction in patients with multiple sclerosis. We also review the use of
      magnetic resonance imaging findings as an outcome measure in clinical trials
      assessing the efficacy of new therapeutic agents for the treatment of multiple
      sclerosis. More advanced applications of magnetic resonance imaging and their use
      in multiple sclerosis is addressed later in the article.

PMID- 9521221
TI  - An overview of the clinical safety profile of atorvastatin (lipitor), a new HMG
      CoA reductase inhibitor.
AB  - BACKGROUND: Statins (3-hydroxy-3-methylglutaryl-coenzyme A [HMG-CoA] reductase
      inhibitors) have been used for a decade to lower low-density lipoprotein (LDL)
      cholesterol levels and to improve cardiovascular disease and clinical outcomes.
      OBJECTIVE: To evaluate the safety profile of atorvastatin (Lipitor). METHODS:
      Data were pooled for 21 completed (2502 patients) and 23 ongoing (1769 patients)
      clinical trials of atorvastatin conducted in US and international community- and
      university-based research centers. In these trials, patients with lipid disorders
      received atorvastatin at dosages of 10 to 80 mg/d. The majority of patients had
      moderate to severe hypercholesterolemia and were treated from 4 weeks to more
      than 24 months. MAIN OUTCOME MEASURES: Transaminase and creatine phosphokinase
      levels and adverse events were recorded. RESULTS: Atorvastatin was well
      tolerated; fewer than 2% of the atorvastatin-treated patients withdrew due to
      drug-attributable adverse events. The overall adverse event profile for
      atorvastatin was similar to that observed with other statins. The most common
      adverse events with atorvastatin as well as with other statins tested were
      constipation, flatulence, dyspepsia, and abdominal pain. Approximately 5% of
      atorvastatin-treated patients had serious adverse events; only 2 of these events
      were possibly associated with treatment. Thirty patients (0.7%) had confirmed
      transaminase elevations greater than 3 times the upper limit of the normal range.
      Most elevations occurred within 16 weeks of beginning treatment. No patients had
      a conclusive characterization of drug-induced myopathy. CONCLUSIONS: The safety
      profile of atorvastatin was consistent with that of all statins tested and was
      similar to that seen in all compounds of this class.

PMID- 9521222
TI  - Trends in the incidence of deep vein thrombosis and pulmonary embolism: a 25-year
      population-based study.
AB  - BACKGROUND: The incidence of venous thromboembolism has not been well described,
      and there are no studies of long-term trends in the incidence of venous
      thromboembolism. OBJECTIVES: To estimate the incidence of deep vein thrombosis
      and pulmonary embolism and to describe trends in incidence. METHODS: We performed
      a retrospective review of the complete medical records from a population-based
      inception cohort of 2218 patients who resided within Olmsted County, Minnesota,
      and had an incident deep vein thrombosis or pulmonary embolism during the 25-year
      period from 1966 through 1990. RESULTS: The overall average age- and sex-adjusted
      annual incidence of venous thromboembolism was 117 per 100000 (deep vein
      thrombosis, 48 per 100000; pulmonary embolism, 69 per 100000), with higher age
      adjusted rates among males than females (130 vs 110 per 100000, respectively).
      The incidence of venous thromboembolism rose markedly with increasing age for
      both sexes, with pulmonary embolism accounting for most of the increase. The
      incidence of pulmonary embolism was approximately 45% lower during the last 15
      years of the study for both sexes and all age strata, while the incidence of deep
      vein thrombosis remained constant for males across all age strata, decreased for
      females younger than 55 years, and increased for women older than 60 years.
      CONCLUSIONS: Venous thromboembolism is a major national health problem,
      especially among the elderly. While the incidence of pulmonary embolism has
      decreased over time, the incidence of deep vein thrombosis remains unchanged for
      men and is increasing for older women. These findings emphasize the need for more
      accurate identification of patients at risk for venous thromboembolism, as well
      as a safe and effective prophylaxis.

PMID- 9521223
TI  - Outcomes in primary Raynaud phenomenon: a meta-analysis of the frequency, rates,
      and predictors of transition to secondary diseases.
AB  - OBJECTIVE: To summarize the current literature on the frequency, rates, types,
      and outcome predictors of secondary diseases that develop in patients with
      primary Raynaud phenomenon. METHODS: A structured MEDLINE literature search with
      the MeSH heading "Raynaud's disease," which was crossed with (1) systemic
      sclerosis, (2) prognosis, (3) prospective studies, (4) follow-up studies, and (5)
      retrospective studies, was used to identify 910 articles for possible inclusion.
      Articles that identified patients with primary Raynaud phenomenon who were
      followed up and re-evaluated at the end of the study, and which used published
      classification criteria to assess the presence or absence of secondary disease
      were included. Patient-years of Raynaud disease, patient-years of follow-up, and
      rates and predictors of transition to secondary disease were calculated from the
      articles selected. The summary odds ratio and positive predictive value for
      evaluation criteria at entry were calculated from 2 x 2 tables generated for each
      variable. RESULTS: Ten articles identified a total of 639 patients with primary
      Raynaud phenomenon who were followed up for 2531 patient-years. Eighty-one
      patients (12.6%) developed a secondary disorder, 80 of which were connective
      tissue diseases. Transitions occurred at a mean rate of 3.2 per 100 patient-years
      of observation. The mean time to develop a secondary disorder was 2.8 years from
      study entry and 10.4 years from the onset of Raynaud phenomenon. At entry, the
      best predictor of transition was an abnormal nailfold capillary pattern (positive
      predictive value, 47%). Antinuclear antibodies in these patients had a positive
      predictive value of only 30%. CONCLUSION: Although a variety of clinical and
      serological abnormalities can be found in patients with primary Raynaud
      phenomenon, only a small percentage of them develop a connective-tissue disease.

PMID- 9521224
TI  - Treatment and outcome of patients with acute myocardial infarction and prior
      cerebrovascular events in the thrombolytic era: the Israeli Thrombolytic National
      Survey.
AB  - BACKGROUND: Patients with a history of stroke presenting with acute myocardial
      infarction (MI) are often excluded from thrombolytic therapy owing to fear of
      intracranial hemorrhage. Few data, however, are available on the risks vs the
      benefits of thrombolysis in patients with an acute MI and a prior cerebrovascular
      event (PCE). METHODS: Data were derived from 2 nationwide surveys of 2012
      consecutive patients with acute MI admitted to all 25 coronary care units in
      Israel during 1992 and 1994. Thrombolytic therapy was given to patients with a
      PCE at the discretion of the treating physicians. Outcomes were compared between
      patients with an acute MI with and without a PCE and between patients with a PCE
      treated with or excluded from thrombolysis. RESULTS: Patients with a PCE (n = 115
      [6%]) were older, with higher rates of atherosclerotic risk factors and in
      hospital complications than their counterparts without a prior event (n = 1897).
      They were treated less often with thrombolysis or mechanical reperfusion. The 1
      year mortality rates were higher among patients with a PCE (28% vs 19%, P<.01),
      but not after multivariate adjustments for clinical characteristics (adjusted
      hazard ratio, 1.08; 95% confidence interval, 0.75-1.55). Patients with an acute
      MI and a PCE who were treated with thrombolysis (n = 29 [25%]) were compared with
      46 patients found ineligible for thrombolysis primarily because of their PCE. The
      timing of the PCE was comparable in both groups (one fifth in the preceding
      year), while prior transient ischemic attacks were more prevalent among patients
      who had undergone thrombolysis. The patients who were treated with thrombolysis
      (n = 29) were older, had a higher rate of anterior infarction, and, while in the
      hospital, received aspirin, anticoagulants, and beta-blockers more often than
      their counterparts (n= 46). In-hospital intracranial hemorrhage did not occur in
      either group. The 1-year mortality rates were 2-fold higher among patients who
      had not undergone thrombolysis compared with those who had (33% vs 18%; adjusted
      hazard ratio, 2.44; 95% confidence interval, 0.78-7.64). CONCLUSIONS: These
      findings, derived from 2 nationwide surveys of consecutive patients with acute
      MI, suggest that patients with PCEs have an adverse outcome attributed to their
      older age and less favorable risk profile. Thrombolytic therapy, however, based
      on our preliminary data, may be beneficial in selected patients with an acute MI
      with a nonrecent PCE.

PMID- 9521225
TI  - Preoperative autologous donation decreases allogeneic transfusion but increases
      exposure to all red blood cell transfusion: results of a meta-analysis.
      International Study of Perioperative Transfusion (ISPOT) Investigators.
AB  - BACKGROUND: Concern about risks associated with allogeneic red blood cell
      transfusion has led to interest in methods of decreasing patient exposure to
      perioperative transfusion. OBJECTIVE: To perform a meta-analysis to determine the
      degree to which predonation of autologous blood reduces patients' exposure to
      allogeneic blood and all transfusions of red blood cells (allogeneic or
      autologous). METHODS: We searched MEDLINE, EMBASE, bibliographies, annual
      reports, press releases, newsletters from organizations with interests in the
      blood system, and personal files for randomized studies and concurrent control
      cohort studies in which the control groups were patients excluded for nonmedical
      reasons. RESULTS: Patients who predonated autologous blood were less likely to
      receive allogeneic blood in the 6 randomized studies (n = 933) (odds ratio [OR],
      0.17; 95% confidence interval [CI], 0.08-0.32) and in the 9 cohort studies (n =
      2351) (OR, 0.19; 95% CI, 0.14-0.26). However, autologous donors were more likely
      to undergo transfusion with allogeneic and/or autologous blood (for randomized
      studies: OR, 3.03; 95% CI, 1.70-5.39 and for cohort studies: OR, 12.32; 95% CI,
      5.90-25.40). Studies that reported use of transfusion protocols found less
      benefit with preoperative autologous donation, although the difference was not
      statistically significant. CONCLUSIONS: Preoperative autologous donation of blood
      decreases exposure to allogeneic blood but increases exposure to any transfusion
      (allogeneic and/or autologous). There is a direct relationship between the
      transfusion rate in the control group and the benefit derived from preoperative
      autologous donation. This suggests that other methods of decreasing blood
      transfusion, such as surgical technique and transfusion protocols, may be as
      important as preoperative autologous donation of blood.

PMID- 9521226
TI  - Diabetes mellitus and cardiovascular disease in women.
AB  - BACKGROUND: Coronary heart disease (CHD) is the leading cause of morbidity and
      mortality in women in the United States. Although CHD is less common in
      premenopausal women than in men, this difference begins to disappear after the
      onset of menopause, presumably related to reduced levels of female sex hormones.
      RESULTS: An association between both a postmenopausal increase in blood pressure
      and CHD that coincide with loss of ovarian function suggests that estrogen and/or
      progesterone may be protective against hypertension and CHD. Diabetes removes the
      normal sex difference in the prevalence of CHD. Increased mortality in women with
      CHD and diabetes compared with women without diabetes has been observed in
      epidemiological studies. CONCLUSIONS: Diabetes appears to obviate the protective
      effects of female sex hormones. Possible reasons for this catastrophic effect of
      diabetes in women are discussed.

PMID- 9521227
TI  - Health-related quality of life in patients served by the Department of Veterans
      Affairs: results from the Veterans Health Study.
AB  - BACKGROUND: The Department of Veterans Affairs Health Care System (VA) is the
      largest integrated single payer system in the United States. To date, there has
      been no systematic measurement of health status in the VA. The Veterans Health
      Study has developed methods to assess patient-based health status in ambulatory
      populations. OBJECTIVES: To describe the health status of veterans and examine
      the relationships between their health-related quality of life, age, comorbidity,
      and socioeconomic and service-connected disability status. METHODS: Participants
      in the Veterans Health Study, a 2-year longitudinal study, were recruited from a
      representative sample of patients receiving ambulatory care at 4 VA facilities in
      the New England region. The Veterans Health Study patients received
      questionnaires of health status, including the Medical Outcomes Study Short Form
      36-Item Health Survey; and a health examination, clinical assessments, and
      medical history taking. Sixteen hundred sixty-seven patients for whom we
      conducted baseline assessments are described. RESULTS: The VA outpatients had
      poor health status scores across all measures of the Medical Outcomes Study Short
      Form 36-Item Health Survey compared with scores in non-VA populations (at least
      50% of 1 SD worse). Striking differences also were found with the sample
      stratified by age group (20-49 years, 50-64 years, and 65-90 years). For 7 of the
      8 scales (role limitations due to physical problems, bodily pain, general health
      perceptions, vitality, social functioning, role limitations due to emotional
      problems, and mental health), scores were considerably lower among the younger
      patients; for the eighth scale (physical function), scores of the young veterans
      (aged 20-49 years) were almost comparable with the levels in the old veterans
      (>65 years). The mental health scores of young veterans were substantially worse
      than all other age groups (P<.001) and scores of screening measures for
      depression were significantly higher in the youngest age group (51%) compared
      with the oldest age groups (33% and 16%) (P<.001). CONCLUSIONS: The VA
      outpatients have substantially worse health status than non-VA populations.
      Mental health differences between the young and old veterans who use the VA
      health care system are sharply contrasting; the young veterans are sicker,
      suggesting substantially higher resource needs. Mental health differences may
      explain much of the worse health-related quality of life in young veterans. As
      health care systems continue to undergo a radical transformation, the Department
      of Veterans Affairs should focus on the provision of mental health services for
      its younger veteran.

PMID- 9521228
TI  - Typhoid fever in the United States, 1985-1994: changing risks of international
      travel and increasing antimicrobial resistance.
AB  - BACKGROUND: Typhoid fever is a potentially fatal illness common in the less
      industrialized world. In the United States, the majority of cases occur in
      travelers to other countries. METHODS: We reviewed surveillance forms submitted
      to the Centers for Disease Control and Prevention, Atlanta, Ga, for patients with
      culture-confirmed typhoid fever between 1985 and 1994. RESULTS: The Centers for
      Disease Control and Prevention received report forms for 2445 cases of typhoid
      fever. Median age of patients was 24 years (range, 0-89 years). Ten (0.4%) died.
      Seventy-two percent reported international travel within the 30 days before onset
      of illness. Six countries accounted for 80% of cases: Mexico (28%), India (25%),
      the Philippines (10%), Pakistan (8%), El Salvador (5%), and Haiti (4%). The
      percentage of cases associated with visiting Mexico decreased from 46% in 1985 to
      23% in 1994, while the percentage of cases associated with visiting the Indian
      subcontinent increased from 25% in 1985 to 37% in 1994. The incidence of typhoid
      fever in US citizens traveling to the Indian subcontinent was at least 18 times
      higher than for any other geographic region. Complete data on antimicrobial
      susceptibility to ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole
      were reported for 330 (13%) Salmonella Typhi isolates. Isolates from 1990 to 1994
      were more likely than isolates from 1985 to 1989 to be resistant to any of these
      antimicrobial agents (30% vs 12%; P<.001) and to be resistant to all 3 agents
      (12% vs 0.6%; P<.001). CONCLUSIONS: American travelers to less industrialized
      countries, especially those traveling to the Indian subcontinent, continue to be
      at risk for typhoid fever. Antimicrobial resistance has increased, and a
      quinolone or third-generation cephalosporin may be the best choice for empirical
      treatment of typhoid fever.

PMID- 9521229
TI  - Complication-free duration and the risk of development of retinopathy in elderly
      diabetic patients.
AB  - BACKGROUND: Determining which diabetic patients are at risk for complications and
      targeting these patients for intensive therapy may avoid the unwanted
      consequences of hypoglycemia in low-risk patients. Since aging is associated with
      a decrease in the incidence of diabetic retinopathy, we assessed whether long
      complication-free duration can define elderly patients at lower risk for future
      development of diabetic retinopathy. METHODS: In a 10-year clinic-based study, we
      studied 833 type 2 diabetic patients who were free of diabetic retinopathy and
      older than 50 years, followed up for more than 4 years. Data included demographic
      and clinical information on arrival, updated every 3 to 6 months, and yearly
      direct ophthalmoscopic examination after pupillary dilation by experienced
      ophthalmologists. All the data were prospectively compiled on relational
      databases. End points studied were presence of retinopathy, nephropathy,
      peripheral neuropathy, peripheral vascular disease, hyperlipidemia, and
      hypertension. RESULTS: Of the patients without retinopathy at the age of 50
      years, 10% developed retinopathy during 4 years of follow-up. These patients had
      longer duration and younger onset of diabetes than the group without retinopathy
      at the 4-year follow-up. Clustering of microvascular and macrovascular
      complications was noted. Discriminant analysis showed the following factors to be
      significant and independent predictors of the development of retinopathy in the
      elderly: duration of diabetes, body mass index, age, and glucose control.
      CONCLUSIONS: A long complication-free period does not define elderly patients
      with type 2 diabetes who are at lower risk for future development of retinopathy.
      On the contrary, the increase in disease duration is significantly associated
      with the development of retinopathy in this age group, as described in younger
      patients.

PMID- 9521230
TI  - A study of the impact of influenza on the functional status of frail older
      people.
AB  - BACKGROUND: Excess hospitalization and death are well-known impacts of influenza
      on older people; however, little is known regarding the impact of influenza on
      functional status. We hypothesized that frail older people are at risk of
      functional decline as an outcome of influenza. OBJECTIVE: To measure the effect
      of acute influenza on the physical and mental status of older patients residing
      in nursing homes. METHODS: Our study was conducted in 6 nursing homes that
      participated in the Medicare Influenza Vaccine Demonstration and experienced
      laboratory-confirmed outbreaks of influenza in 1991 and 1992. A case-comparison
      design was used. One hundred sixteen of 131 residents who developed influenza
      like illness and survived at least 4 months served as the case subjects; 127 of
      132 residents without influenza-like illness who survived served as the
      comparison subjects. Measures of functional status 1 to 2 months before outbreak
      and 1 to 2 months and 3 to 4 months after outbreak were collected from medical
      records. Matched pairs analyses were conducted to ascertain changes in selected
      measures of functional status within each of the study groups. Wilcoxon signed
      rank tests for statistical significance were used. RESULTS: Among surviving case
      subjects and comparison subjects, 25% and 15.7%, respectively, experienced
      decline in at least 1 major function (P=.04). Case subjects experienced
      significant decline in independence in bathing, dressing, and mobility while
      comparison subjects experienced decline in mental status. CONCLUSIONS: Within the
      limitations of this study, influenza is observed to cause decline in major
      physical functions in more than 9% of survivors. Such disabling outcomes
      constitute an important new measure of impact of influenza on the frail elderly.

PMID- 9521231
TI  - Estimating the benefits of modifying risk factors of cardiovascular disease: a
      comparison of primary vs secondary prevention.
AB  - OBJECTIVES: To compare the potential years of life saved (YOLS) associated with
      risk factor modification in the primary and secondary prevention of
      cardiovascular disease (CVD). METHODS: The CVD life expectancy model estimates
      the risk of death due to coronary disease, stroke, and other causes based on the
      levels of independent risk factors (such as age, blood pressure, and blood lipid
      levels) found in the cohort of the Lipid Research Clinics. The model was
      validated by comparing its predictions with the observed fatal outcomes of 9
      randomized clinical trials. We then estimated the YOLS associated with treating
      hyperlipidemia or hypertension among hypothetical patient groups with and without
      CVD at baseline. We defined high-risk patients as those with 3 risk factors
      (hyperlipidemia, cigarette smoking, and hypertension) and low-risk patients as
      those with isolated hypertension or hyperlipidemia. RESULTS: The fatal events
      predicted by the model were consistent with the clinical trial results. Among men
      and women with hyperlipidemia without CVD, the forecasted benefits of lipid
      therapy were substantially greater among high-risk groups vs low-risk groups
      (4.74-0.78 YOLS vs 2.50-0.25 YOLS, respectively). Among those with CVD, the
      forecasted benefits of treatment were similar for both high-risk and low-risk
      groups (4.65-0.65 YOLS vs 3.84-0.58 YOLS, respectively). The results for
      hypertension therapy also demonstrated greater benefits for high-risk vs low-risk
      patients undergoing primary prevention therapy (1.34-0.29 YOLS vs 0.85-0.13 YOLS,
      respectively), and the forecasted benefits in secondary prevention were similar
      (1.26-0.23 YOLS vs 1.00-0.23 YOLS, respectively). CONCLUSIONS: The clinical
      approach to risk factor modification in primary prevention should be different
      from that in secondary prevention. The forecasted benefits of therapy among
      patients without CVD are greatest in the presence of other risk factors. Among
      those with CVD, the benefits of therapy are equivalent, thereby obviating the
      need to target high-risk patients.

PMID- 9521232
TI  - Effect of vitamin E and beta carotene on the incidence of primary nonfatal
      myocardial infarction and fatal coronary heart disease.
AB  - BACKGROUND: Oxidized low-density lipoprotein is involved in the pathogenesis of
      atherosclerosis. In epidemiological studies antioxidants have been inversely
      related with coronary heart disease. Findings from controlled trials are
      inconclusive. METHODS: We studied the primary preventive effect of vitamin E
      (alpha tocopherol) and beta carotene supplementation on major coronary events in
      the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, a controlled trial
      undertaken primarily to examine the effects of these agents on cancer. A total of
      27 271 Finnish male smokers aged 50 to 69 years with no history of myocardial
      infarction were randomly assigned to receive vitamin E (50 mg), beta carotene (20
      mg), both agents, or placebo daily for 5 to 8 years (median, 6.1 years). The end
      point was the first major coronary event, either nonfatal myocardial infarction
      (surviving at least 28 days; n = 1204) or fatal coronary heart disease (n = 907).
      RESULTS: The incidence of primary major coronary events decreased 4% (95%
      confidence interval, -12% to 4%) among recipients of vitamin E and increased 1%
      (95% confidence interval, -7% to 10%) among recipients of beta carotene compared
      with the respective nonrecipients. Neither agent affected the incidence of
      nonfatal myocardial infarction. Supplementation with vitamin E decreased the
      incidence of fatal coronary heart disease by 8% (95% confidence interval, -19% to
      5%), but beta carotene had no effect on this end point. CONCLUSIONS:
      Supplementation with a small dose of vitamin E has only marginal effect on the
      incidence of fatal coronary heart disease in male smokers with no history of
      myocardial infarction, but no influence on nonfatal myocardial infarction.
      Supplementation with beta carotene has no primary preventive effect on major
      coronary events.

PMID- 9521233
TI  - Acute pulmonary edema after overdrive for atrial flutter.

PMID- 9521234
TI  - Costs of occupational injury and illness in the United States.

PMID- 9521235
TI  - The benefits of performing autopsies.

PMID- 9521236
TI  - Prevalence of parvovirus B19 infection among patients with human immunodeficiency
      virus infection in Barcelona, Spain.

PMID- 9521237
TI  - Progressive proximal spinal and bulbar muscular atrophy of late onset: a sex
      linked recessive trait.

PMID- 9521238
TI  - Measurement of quality in health care.

PMID- 9521240
TI  - Ethical issues in clinical research in neurology: advancing knowledge and
      protecting human research subjects. The Ethics and Humanities Subcommittee of the
      American Academy of Neurology.

PMID- 9521239
TI  - Drop the Alzheimer's drop test.

PMID- 9521241
TI  - Assisted suicide, euthanasia, and the neurologist. The Ethics and Humanities
      Subcommittee of the American Academy of Neurology.

PMID- 9521242
TI  - Factors determining the therapeutic window for stroke.
AB  - The duration of the window to treat acute cerebral ischemia has become an
      important question since the first effective drug for stroke victims has become
      available. Statistical analysis of relevant animal studies suggests that
      irreversible focal injury begins within a few minutes and is complete within
      about 6 hours. There will be substantial difficulties in attempting to obtain
      accurate estimates of the duration of ischemia that causes permanent damage in
      patients unless technical obstacles are overcome. Empirical estimates of the
      therapeutic window for stroke can be obtained from properly designed clinical
      trials, but optimal care will continue to necessitate urgent treatment.

PMID- 9521243
TI  - Oculomotor abnormalities in schizophrenia: a critical review.
AB  - Oculomotor abnormalities, particularly in smooth pursuit tracking, are one of the
      most widely investigated biological markers of schizophrenia. However, despite
      the wealth of published data, important questions concerning the exact nature of
      these abnormalities remain unanswered. Many of the studies use unreliable
      methodology, and few attempts have been made to interpret the observed oculomotor
      dysfunction in terms of current understanding of eye movement physiology. Also,
      the potential effects of antipsychotic medication have been poorly addressed.
      Recent research, using more reliable measurement techniques and novel saccadic
      paradigms are producing important results and may provide a more productive
      framework for future studies of oculomotor abnormalities in schizophrenia.

PMID- 9521244
TI  - Does the neurologist add value to the carotid endarterectomy patient?

PMID- 9521245
TI  - Vigabatrin-associated retinal cone system dysfunction: electroretinogram and
      ophthalmologic findings.
AB  - OBJECTIVE: To determine the sources of vigabatrin-associated visual disturbances
      in patients treated for epilepsy. BACKGROUND: Vigabatrin is an extremely
      effective antiepileptic drug that selectively increases brain gamma-aminobutyric
      acid (GABA). Several patients recently developed constricted visual fields during
      vigabatrin treatment in the United Kingdom, indicating the possibility of GABA
      associated retinal dysfunction. METHODS: Patients with visual symptoms treated
      chronically with vigabatrin at our center underwent visual evoked potentials
      (VEP), electroretinograms (ERG), and visual field and ophthalmologic
      examinations. RESULTS: Four of 38 patients treated with vigabatrin developed
      visual symptoms 2 to 40 months after starting the drug. Two patients complained
      of constricted visual fields and two had blurred vision. ERG demonstrated
      evidence of bilateral retinal dysfunction consistent with reduced inner retinal
      cone response in all four patients. Oscillatory potential responses were lost,
      suggesting impairment of the highly GABAergic amacrine cells. Two of the patients
      had normal VEPs and minimal findings on clinical ophthalmology examinations
      despite abnormal ERGs. Abnormal examination findings were narrowed retinal
      arteries, surface wrinkling retinopathy, and abnormal macular reflexes. One
      patient also had reduced rod photoreceptor function in the more symptomatic left
      eye. CONCLUSIONS: Visual field constriction and blurring during vigabatrin
      therapy is associated with retinal cone system dysfunction. Visual symptoms may
      represent selective vulnerability of retinas of affected patients to GABAergic
      effects of vigabatrin. The prevalence and course of retinal changes associated
      with vigabatrin therapy are important to determine in a larger group of patients.

PMID- 9521246
TI  - Is in-hospital stroke mortality an accurate measure of quality of care?
AB  - We examined the validity of using in-hospital stroke mortality as predicted by
      the Cleveland Hospital Outcomes Indicators of Care Evaluations (CHOICE) model as
      a measure of quality of care. A total of 223 patients admitted to the hospital
      for stroke were evaluated by the CHOICE model, which predicted that 19 stroke
      deaths would occur. We reviewed the 19 patients with the highest predicted
      mortality, according to CHOICE, and three additional patients who died following
      stroke. We found that The CHOICE model accurately predicts in-hospital stroke
      mortality for large populations but not for individual patients. CHOICE and other
      stroke outcome models rely heavily on early Do Not Resuscitate orders and coma
      but exclude important variables found in the literature on stroke. No correlation
      between in-hospital stroke mortality and quality of care was demonstrated.
      Mortality prediction models used to guide consumers on where to receive stroke
      care are potentially misleading, as they do not assess functional neurologic
      recovery or the process of care that are essential elements of quality.

PMID- 9521247
TI  - Streptokinase in acute stroke: effect on reperfusion and recanalization.
      Australian Streptokinase Trial Study Group.
AB  - The Australian Streptokinase Trial was a randomized, double-blind, placebo
      controlled trial, in which streptokinase (SK, 1.5 million IU I.V.) was given
      within 4 hours of stroke onset. In a subset of 37 patients, 99mTc-labeled D,L
      hexamethylpropylene amine oxime single-photon emission computed tomography
      (SPECT) and/or transcranial Doppler (TCD) studies were performed before and after
      therapy to test the hypothesis that SK may improve the hemodynamic measures of
      reperfusion/recanalization rates (TCD parameter) within 24 hours. Eighteen
      patients received SK and 19 placebo. Baseline characteristics were similar in
      both groups, and there were no differences in clinical outcomes assessed at 3
      months after stroke. Although there was no increase in the group mean perfusion
      defect or volume on SPECT after thrombolytic therapy, a larger number of patients
      demonstrating the combined end point of reperfusion or recanalization was seen in
      the SK group (13/14, 93%) than in the placebo group (7/14, 50%; p = 0.01).
      Although SK given within 4 hours of acute ischemic stroke appears to improve
      arterial patency/tissue reperfusion, this effect is neither early nor extensive
      enough to influence overall clinical outcome.

PMID- 9521248
TI  - Noninvasive MRI evaluation of cerebral blood flow in cerebrovascular disease.
AB  - Previous studies have demonstrated that cerebral blood flow (CBF) can be assessed
      noninvasively by MRI using magnetic labeling of arterial water as a diffusible
      flow tracer. The purpose of this study was to assess the quality of CBF images
      obtained from patients with cerebrovascular disease using this method, and to
      begin to evaluate the potential clinical role for this technique. We recruited 14
      patients who presented with stroke, TIA, or severe carotid stenosis and were
      likely to have altered CBF based on clinical assessment. In many of these
      patients, CBF imaging disclosed both focal and hemispheric hypoperfusion, either
      in vascular territories or in watershed regions. In 11 patients with significant
      proximal arterial stenosis, hemispheric CBF abnormalities localized to the side
      of most significant stenosis for the anterior circulation distribution. In
      several patients watershed hypoperfusion was even more pronounced. Our results
      suggest that good-quality MR CBF images can be obtained reliably from patients
      with cerebrovascular disease. CBF imaging can be combined with standard
      structural imaging within a single MRI examination, and provides clinically
      meaningful information. The capability of measuring CBF easily provides a
      potentially useful tool for clinical assessment and further investigation of
      stroke pathophysiology.

PMID- 9521249
TI  - Is videopupillography useful in the diagnosis of Alzheimer's disease?
AB  - Patients with Alzheimer's disease (AD) reportedly exhibit greater pupillary
      dilation than healthy subjects in response to tropicamide. By means of
      videopupillography, we have found that the average basal pupillary diameter was
      greater in AD patients than in normal controls and that there is an inverse
      relationship between the average pupillary diameter and the maximal dilation
      obtained following tropicamide application in both groups. Pupillary response to
      tropicamide and videopupillography do not distinguish between Alzheimer's
      patients and controls.

PMID- 9521250
TI  - A randomized, double-blind, placebo-controlled trial of deprenyl and thioctic
      acid in human immunodeficiency virus-associated cognitive impairment. Dana
      Consortium on the Therapy of HIV Dementia and Related Cognitive Disorders.
AB  - Cognitive impairment is a frequent manifestation of advanced human
      immunodeficiency virus (HIV) infection. The response to antiretroviral medication
      is often partial and poorly sustained. Recent studies suggest that free radical
      production within the CNS and neuronal apoptosis may play important roles in the
      pathogenesis of HIV dementia. We conducted a randomized double-blind, placebo
      controlled trial using a parallel group, 2 x 2 factorial design evaluating
      deprenyl, a monoamine oxidase B inhibitor and putative anti-apoptotic agent, and
      thioctic acid, an antioxidant, in 36 patients with HIV-associated cognitive
      impairment. Both deprenyl and thioctic acid were well tolerated with few adverse
      events. Deprenyl recipients showed significant improvement on tests of verbal
      memory compared with patients not taking deprenyl. Thioctic acid treatment did
      not improve cognitive function. These results suggest that deprenyl treatment is
      associated with cognitive improvement in subjects with mild HIV-associated
      cognitive impairment, whereas thioctic acid has no benefit. A larger efficacy
      trial is needed to assess the long-term effect of deprenyl on cognitive
      performance in patients with HIV infection.

PMID- 9521251
TI  - Paraneoplastic and oncologic profiles of patients seropositive for type 1
      antineuronal nuclear autoantibodies.
AB  - Type 1 antineuronal nuclear autoantibody (ANNA-1, also known as "anti-Hu") is a
      marker of neurologic autoimmunity that is highly associated with small-cell lung
      carcinoma (SCLC). To determine the spectrum of symptoms and signs as well as the
      frequency of cancer in adult patients who are seropositive for ANNA-1, we
      reviewed 162 sequential patients (67% female) identified as ANNA-1-positive in a
      comprehensive immunofluorescence screening test. In 21% of these patients, the
      antibody test requested by the physician was not ANNA-1. By the end of the follow
      up period, cancer had been found in 142 patients (88%). Ten of these lacked
      evidence of SCLC (4 had prostate carcinoma, 3 breast carcinoma, 1 both prostate
      carcinoma and melanoma, 1 lymphoma, and 1 squamous-cell lung carcinoma). Of the
      132 patients (81%) with proven SCLC, 17 had one or more coexisting malignant
      neoplasms (6 had renal carcinoma, 4 another lung primary carcinoma, 3 prostate
      carcinoma, 3 breast carcinoma, and 4 assorted neoplasms). The diagnosis of SCLC
      in 128 patients (97%) followed the onset of paraneoplastic symptoms. SCLC was
      identified in 10 patients by chest MRI after an equivocal chest radiograph or CT;
      in 28 by bronchoscopy, mediastinoscopy, or thoracotomy; and in 7 at autopsy.
      Neurologic signs in decreasing frequency were neuropathy (sensory > mixed somatic
      > autonomic > cranial [especially cranial nerve VIII] > motor), cerebellar
      ataxia, limbic encephalitis, polyradiculopathy, associated Lambert-Eaton
      myasthenic syndrome, myopathy, myelopathy, opsoclonus/myoclonus, motor
      neuronopathy, brachial plexopathy, and aphasia. Nineteen patients had a solely
      gastrointestinal initial presentation, including gastroparesis, pseudo
      obstruction, esophageal achalasia, or other dysmotility. We conclude that
      seropositivity for ANNA-1 can expedite the diagnosis and treatment of otherwise
      occult cancer in patients, especially tobacco abusers, with varied neurologic and
      gastroenterologic presentations. The search for SCLC should not end on
      discovering a different neoplasm.

PMID- 9521252
TI  - Progressive ventral posterior cortical degeneration presenting as alexia for
      music and words.
AB  - Patients with posterior cortical atrophy may have dorsal visual system (occipital
      parietal) dysfunction (optic ataxia, visuospatial disorientation, and
      simultanagnosia), ventral visual system (occipital-temporal) dysfunction (pure
      alexia, prosopagnosia, visual anomia, and agnosia), or both. We report a
      professional musician with ventral system dysfunction whose first symptom was
      alexia for music. Subsequently, she developed pure alexia for words but had
      preserved sorting of words. These observations suggest that the ventral visual
      system is important in music and word reading. However, sorting of words may be
      mediated by the dorsal visual system.

PMID- 9521253
TI  - L-deprenyl in Alzheimer's disease: cognitive and behavioral effects.
AB  - BACKGROUND: Short-term studies of L-deprenyl in Alzheimer's disease (AD) suggest
      a beneficial effect, whereas longer-term studies are less convincing.
      Accordingly, we undertook a 6-month, randomized, double-blind, placebo-controlled
      clinical trial to assess the potential benefit of L-deprenyl in AD. METHODS:
      Sixty subjects were assigned to L-deprenyl (10 mg daily) or placebo. After 4
      weeks of single-blind placebo, 51 subjects entered the double-blind phase. The
      Brief Psychiatric Rating Scale (BPRS) was the primary outcome measure. Secondary
      outcome measures were the Mini-Mental State Examination, Global Deterioration
      Scale, Alzheimer's Disease Assessment Scale (noncognitive), Cornell Scale for
      Depression in Dementia, Buschke Selective Reminding Test (BSRT), Relative's
      Assessment of Global Symptomatology-Elderly (RAGS-E), Controlled Oral Word
      Association Test, and Modified Continuous Performance Test. In addition, several
      exploratory tasks were included for future hypothesis testing. RESULTS: We found
      no significant differences between the L-deprenyl and placebo groups on the
      primary or secondary measures. However, several measures appeared to be sensitive
      to change over time, including the total score on the BPRS and some of its
      components as well as parts of the BSRT and the RAGS-E. CONCLUSION: Oral L
      deprenyl provides no detectable benefit on general behavior, neuropsychiatric
      symptoms, or cognitive function in AD after 6 months of treatment. Protocols for
      future drug studies should utilize measures that are sensitive to change over
      time such as the BPRS.

PMID- 9521255
TI  - Second impact syndrome.
AB  - Diffuse cerebral swelling with delayed catastrophic deterioration, a known
      complication of brain trauma, has been postulated to occur after repeated
      concussive brain injury in sports--the "second impact syndrome" (SIS). Certain
      current concussion management guidelines are contingent upon this assumption. We
      established criteria for definite, probable, and possible SIS and analyzed all
      published cases. A total of 17 cases were identified in which the reports
      described the cases as being consistent with SIS. Of these, only five probable
      cases of SIS were found based on our diagnostic criteria. We also studied the
      accuracy of recalled episodes of minor concussion in football players by their
      teammates because the diagnosis of SIS is usually based on such accounts. We
      found overreporting of recalled episodes of concussion in teammates when compared
      with self reports and videotape analysis. Based on case reports, the claim that
      SIS is a risk factor for diffuse cerebral swelling is not established. Prevention
      strategies for sports-related cerebral swelling are difficult to implement in the
      absence of established risk factors.

PMID- 9521254
TI  - Treatment outcome of tacrine therapy depends on apolipoprotein genotype and
      gender of the subjects with Alzheimer's disease.
AB  - We studied the effects of apolipoprotein E (APOE) genotype and gender on clinical
      response to tacrine in patients with mild to moderate Alzheimer's disease (AD).
      We analyzed data from a previously reported 30-week, double-blind, placebo
      controlled trial of tacrine, in which APOE genotypes were determined from
      previously collected plasma samples. Patients were assigned to placebo or tacrine
      with daily dosages of 80, 120, or 160 mg/day. The outcome measures were
      Alzheimer's Disease Assessment Scale-Cognitive Component, Clinician Interview
      Based Impression, Mini-Mental State Examination, and the Caregiver-rated Clinical
      Global Impression of Change. An intent-to-treat (ITT) analysis of patients with
      available genotypes (n = 528) did not reveal response differences by genotype,
      although the effect size was twice as large in the epsilon2-3 as the epsilon4
      group (-2.62 versus -1.25). The association of treatment effect with APOE
      genotype varied significantly according to gender (p < 0.002 for ITT; p < 0.05
      for evaluables). The treatment effect was larger in the epsilon2-3 compared with
      epsilon4 women (ITT, 4.24 points, p = 0.03; evaluable, 7.20 points, p = 0.01). In
      contrast, treatment effect size was not different between epsilon2-3 and epsilon4
      of men with AD. APOE genotype and gender may predict response to tacrine in
      patients with AD.

PMID- 9521256
TI  - Creutzfeldt-Jakob disease in a husband and wife.
AB  - A 53-year-old man died of sporadic Creutzfeldt-Jakob disease (CJD) after a 1.5
      year clinical course. Four and a half years later, his then 55-year-old widow
      died from CJD after a 1-month illness. Both patients had typical clinical and
      neuropathologic features of the disease, and pathognomonic proteinase-resistant
      amyloid protein ("prion" protein, or PrP) was present in both brains. Neither
      patient had a family history of neurologic disease, and molecular genetic
      analysis of their PrP genes was normal. No medical, surgical, or dietary
      antecedent of CJD was identified; therefore, we are left with the unanswerable
      alternatives of human-to-human transmission or the chance occurrence of sporadic
      CJD in a husband and wife.

PMID- 9521257
TI  - Fatal familial insomnia: genetic, neuropathologic, and biochemical study of a
      patient from a new Italian kindred.
AB  - Fatal familial insomnia (FFI) is an inherited prion disease linked to a mutation
      at codon 178 of the PRNP gene that results in aspartic acid to asparagine
      substitution, in coupling phase with methionine at position 129. The disease is
      characterized clinically by insomnia with disturbances of the autonomic,
      endocrine, and motor systems and neuropathologically by selective degeneration of
      the thalamus. Phenotypic variability is well known and has been linked to
      homozygosity or heterozygosity at PRNP codon 129. We report the clinical,
      neuropathologic, and biochemical findings and genomic analysis of a patient with
      FFI from a new Italian kindred. Although homozygous for methionine at codon 129,
      this patient showed some clinical and pathologic features most commonly found in
      heterozygotes.

PMID- 9521258
TI  - Diagnosis of cytomegalovirus encephalitis in patients with AIDS by quantitation
      of cytomegalovirus genomes in cells of cerebrospinal fluid.
AB  - A nested polymerase chain reaction (PCR) assay was used to determine the levels
      of cytomegalovirus (CMV) genomes in cells of CSF from 19 patients with AIDS and
      12 human immunodeficiency virus type I (HIV-1) seronegative individuals with
      various neurologic disorders. Five AIDS patients had autopsy-proven CMV
      encephalitis (CMVE) and 14 patients had no evidence of CMV-related CNS
      manifestations. CSF cells from AIDS patients with confirmed CMVE harbored viral
      genomes at a median value of 3,333/10(5) cells (range, 1,667 to 5,333/10(5)
      cells; mean, 3,558/10(5) cells) compared with a median value of 125/10(5) cells
      (range, 9 to 1,000/10(5) cells; mean, 281/10(5) cells) for AIDS patients with CMV
      unrelated symptoms and a median value of 1.9/10(5) cells (range, 0 to 562/10(5)
      cells; mean, 52/10(5) cells) for HIV-1 seronegative control subjects. A subset of
      CSF samples was assessed using a modified single round amplification PCR with a
      detection limit of 500 viral copies. CMV DNA was detected in all four specimens
      from AIDS patients with proven CMVE, in two of five AIDS patients without CMVE,
      and in none of five seronegative control subjects. Quantitation of CMV genomes in
      CSF cells is indicative of latent or productive CMV infection and is a reliable
      means for diagnosis of CMVE in patients with AIDS. Detection of a cutoff value of
      cellular CMV genomes by means of nonquantitative PCR may identify patients at
      risk for CMV infection of the CNS.

PMID- 9521259
TI  - Long-term progression in chronic manganism: ten years of follow-up.
AB  - We studied the long-term clinical course of five patients with chronic manganese
      intoxication. The mean scores of the King's College Hospital Rating Scale for
      Parkinson's disease increased from 15.0 +/- 4.2 in 1987 to 28.3 +/- 6.70 in 1991
      and then to 38.1 +/- 12.9 in 1995. The deterioration was most prominent in gait,
      rigidity, speed of foot tapping, and writing. Tissue concentrations of manganese
      in blood, urine, scalp hair, and pubic hair returned to normal. Follow-up MRIs
      did not show paramagnetic high-signal intensity on T1-weighted images. The data
      indicate that clinical progression in patients with manganese parkinsonism
      continues even 10 years after cessation of exposure.

PMID- 9521261
TI  - Optic neuritis: prognosis for multiple sclerosis from MRI, CSF, and HLA findings.
AB  - We investigated the paraclinical profile of monosymptomatic optic neuritis (ON)
      and its prognosis for multiple sclerosis (MS). The correct identification of
      patients with very early MS carrying a high risk for conversion to clinically
      definite MS is important when new treatments are emerging that hopefully will
      prevent or at least delay future MS. We conducted a prospective single observer
      and population-based study of 147 consecutive patients (118 women, 80%) with
      acute monosymptomatic ON referred from a catchment area of 1.6 million
      inhabitants between January 1, 1990 and December 31, 1995. Of 116 patients
      examined with brain MRI, 64 (55%) had three or more high signal lesions, 11 (9%)
      had one to two high signal lesions, and 41 (35%) had a normal brain MRI. Among
      143 patients examined, oligoclonal IgG (OB) bands in CSF only were demonstrated
      in 103 patients (72%). Of 146 patients analyzed, 68 (47%) carried the
      DR15,DQ6,Dw2 haplotype. During the study period, 53 patients (36%) developed
      clinically definite MS. The presence of three or more MS-like MRI lesions as well
      as the presence of OB were strongly associated with the development of MS (p <
      0.001). Also, Dw2 phenotype was related to the development of MS (p = 0.046). MRI
      and CSF studies in patients with ON give clinically important information
      regarding the risk for future MS.

PMID- 9521260
TI  - Extended use of glatiramer acetate (Copaxone) is well tolerated and maintains its
      clinical effect on multiple sclerosis relapse rate and degree of disability.
      Copolymer 1 Multiple Sclerosis Study Group.
AB  - When 251 relapsing-remitting patients with multiple sclerosis were randomized to
      receive daily subcutaneous injections of glatiramer acetate, previously called
      copolymer 1 (Copaxone; n = 125) or placebo (n = 126) for 24 months, there were no
      laboratory abnormalities associated with glatiramer acetate treatment and it was
      well tolerated with few side effects. Patients receiving glatiramer acetate had
      significantly fewer relapses and were more likely to be neurologically improved,
      whereas those receiving placebo were more likely to worsen. This study was
      extended for 1 to 11 months (mean of 5.2 months for the glatiramer acetate group
      and 5.9 months for the placebo group). The blinding and study conditions used
      during the core 24-month study were unchanged throughout the extension. The
      results of this extension study confirm the excellent tolerance and safety
      profile of glatiramer acetate for injection. The clinical benefit of glatiramer
      acetate for both the relapse rate and for neurologic disability was sustained at
      the end of the extension trial.

PMID- 9521262
TI  - Multimodality visual evoked potentials in evaluating visual dysfunction in optic
      neuritis.
AB  - Visual information is processed via multiple, parallel channels. The present
      study examined the clinical feasibility of multimodality visual evoked potentials
      (VEPs) in optic neuritis. We recorded transient VEPs to 30' checkerboard
      patterns, chromatic and achromatic sinusoidal gratings and apparent motion, and
      steady-state VEPs to achromatic gratings in 15 normal controls and 14 patients.
      VEPs to 30' checks were abnormal in 10 eyes (7 patients); however, considering
      all five modalities, abnormal responses were seen in 20 eyes (12 patients).
      Abnormality rates were not equal among the visual stimuli, which thus suggested
      possible dysfunction of individual subdivisions in the visual pathways. We
      conclude that use of multimodality VEPs may increase both understanding of the
      pathophysiology of the visual pathways and diagnostic yield.

PMID- 9521263
TI  - Effect of age at onset and parental disease status on sibling risks for MS.
AB  - MS is believed to be a complex trait determined by genetic and nongenetic
      factors. Data suggest that MS susceptibility and age at onset are each, at least
      to some extent, under genetic control. The present study carefully examined five
      covariates (sex of the index case, sex of the sibling, birth cohort of the
      sibling [< or = 1919, 1920 to 1939, > or = 1940], age of MS onset in the index
      patient (< or = 20 years, 21 to 30 years, 31 to 40 years, > 40 years), and MS
      disease status of the parents [i.e., MS present in one parent or no parent with
      MS]) that may influence the familial risk of MS in a large cohort of 1,896 MS
      patients and 8,878 of their first-degree relatives. Of these, sex of the sibling,
      parental MS status, and index patient onset age were the important factors
      influencing MS risks to siblings. The results of this study are (1) the index
      patient-onset-age effect suggests that individuals with a greater genetic loading
      (i.e., a greater contribution of susceptibility alleles) have an earlier age at
      onset and (2) genetic loading is substantially increased in individuals with an
      affected parent. These data are important both for genetic counseling and gene
      identification studies.

PMID- 9521264
TI  - Randomized prospective study of early discontinuation of antiepileptic drugs in
      children with epilepsy.
AB  - We studied recurrence rate, risk factors for recurrence, and outcome after
      recurrence in children after early withdrawal of antiepileptic drugs (AEDs). One
      hundred sixty-one children with newly diagnosed epilepsy who had become seizure
      free within 2 months after starting treatment and remained so for 6 months were
      randomly assigned to immediate withdrawal of AEDs (n = 78) or continuation of
      treatment for another 6 months followed by withdrawal (n = 83). The probability
      of remaining seizure free at 24 months after randomization was 51% (95% CI, 40 to
      62) in Group A and 52% (41 to 63) in Group B. Significant predictive factors for
      relapse were partial epilepsy, seizure onset at 12 years or older, defined
      etiology, and epileptiform EEG before randomization. At the end of follow-up
      (median, 41.9 months), 129 children (80.6%) had a terminal remission of at least
      1 year, 88 without AEDs and 41 with AEDs. No significant difference in outcome
      was found between Groups A and B. In children with epilepsy and an early response
      to therapy, AED withdrawal after 6 or 12 months of treatment leads to seizure
      recurrence in approximately half of all patients regardless of the duration of
      therapy. More than 60% of those with one or more recurrences reach a terminal
      remission of at least 1 year after long-term follow-up with or without AEDs.

PMID- 9521265
TI  - Double pathology in Rasmussen's syndrome: a window on the etiology?
AB  - The syndrome of chronic encephalitis with epilepsy (Rasmussen's syndrome)
      typically occurs in children and is characterized by the development of
      intractable focal seizures, progressive hemiparesis and intellectual
      deterioration. The etiology is unknown, and the pathological abnormalities vary
      from those of active disease, with numerous microglial nodules, with or without
      neuronophagia, perivascular round cells and glial scarring, to those of remote
      disease, demonstrated by neuronal loss, gliosis and perivascular round cells but
      few microglial nodules. We describe five patients presenting with clinical
      features typical of Rasmussen's syndrome, in whom pathological examination showed
      a second, previously unsuspected pathology in addition to the changes of chronic
      encephalitis. Two of the patients had vascular abnormalities bearing some
      resemblance to cavernous angiomata, one had a tumor, one had tuberous sclerosis,
      and one the forme fruste of tuberous sclerosis. The coexistence of a second
      pathology in these patients may provide information about the underlying
      mechanism of this rare condition.

PMID- 9521266
TI  - Incidence of status epilepticus in Rochester, Minnesota, 1965-1984.
AB  - We determined the incidence of status epilepticus (SE) by ascertaining all first
      episodes of SE in Rochester, Minnesota through the Rochester Epidemiology
      Project's records-linkage system between January 1, 1965 and December 31, 1984.
      Information was collected on age, gender, duration, seizure type, and etiology.
      The age-adjusted incidence of SE was 18.3 per 100,000 population. SE incidence
      was U-shaped, peaking under 1 year and over 60 years of age. The incidence of SE
      was greater for males than for females, for acute symptomatic etiology than any
      other etiology, and for partial SE that did not generalize than any other seizure
      type. Status of long duration (at least 2 hours) occurred more frequently among
      infants and the elderly than among persons aged 1 to 65 years. Cumulative
      incidence was 4 per 1,000 to age 75 and showed the greatest increase after age
      60. Given the aging of the population, SE will become an increasingly important
      public health problem.

PMID- 9521267
TI  - Clinical seizure lateralization in mesial temporal lobe epilepsy: differences
      between patients with unitemporal and bitemporal interictal spikes.
AB  - OBJECTIVE: To compare the reliability of clinical seizure lateralization in
      temporal lobe epilepsy patients with unitemporal and bitemporal independent
      interictal spikes and unilateral hippocampal atrophy or sclerosis (HA/HS) on MRI
      scan. PATIENTS AND METHODS: We studied 11 patients with unitemporal and 10
      patients with bitemporal interictal spikes. We calculated a spike ratio by
      dividing the number of spikes ipsilateral to the side of HA/HS by those occurring
      contralaterally. RESULTS: Clinical seizure lateralization was correct, i.e.,
      ipsilateral to the side of HA/HS, significantly more often in the unitemporal
      group. Spike ratios were significantly higher in seizures that were lateralized
      correctly as compared with both incorrectly and nonlateralized seizures. Within
      the individual patients, a significant positive correlation between spike ratios
      and the proportion of correctly lateralized seizures was found. We identified
      three categories of symptoms according to lateralization accuracy. Category 1
      symptoms (version, postictal paresis, and early ictal vomiting/retching)
      lateralized to the side of HA/HS in 100% of patients in the uni- and bitemporal
      groups. Category 2 symptoms (dystonic posturing, mouth deviation, postictal
      dysnomia/dysphasia, and ictal speech) provided a 100% correct lateralization in
      the unitemporal but not in the bitemporal patients. Category 3 symptoms
      (nonversive early head turning and unilateral upper extremity automatisms)
      yielded erroneous lateralization in both patient groups. CONCLUSIONS: We conclude
      that reliable clinical seizure lateralization in mesial temporal lobe epilepsy
      can only be achieved in patients with unitemporal interictal spikes, whereas
      clinical lateralization in patients with bitemporal spikes must be viewed
      cautiously.

PMID- 9521268
TI  - Temporal lobe developmental malformations and epilepsy: dual pathology and
      bilateral hippocampal abnormalities.
AB  - Temporal lobe developmental malformations (TLDM) with focal cortical dysplasia
      and balloon cells may coexist with mesial temporal sclerosis. The true incidence
      of this dual pathology is unknown. Our aim was to assess the frequency of
      amygdala (AM)-hippocampal abnormality in a homogeneous population with this
      specific developmental malformation. MRI-based volumetry of the AM and
      hippocampal formation (HF) in 30 patients with unilateral TLDM and intractable
      partial epilepsy was performed. A volume normalization process defined a normal
      range of HF and AM volumes in control subjects, and enabled the detection of
      bilateral volume loss. Normalized volumes detected HF atrophy in 26 patients
      (nine unilateral and 17 bilateral) and AM atrophy in 18 patients (three
      unilateral and 15 bilateral). Visual analysis detected unilateral HF abnormality
      in 21 patients and bilateral abnormality in two. When compared with a group of
      patients with temporal lobe epilepsy and pure hippocampal sclerosis (N = 92),
      where volumetry revealed bilateral HF atrophy in 18%, a significant difference in
      the frequency of bilateral HF atrophy was found (p < 0.0001). Dual pathology is
      frequent in patients with TLDM (87%), and the AM-HF abnormality is often
      bilateral (57%). Our data suggest that more widespread and potentially
      epileptogenic lesions coexist with visibly detectable unilateral TLDM. This has
      implications for the selection of patients for temporal lobe surgery and may
      influence surgical strategies.

PMID- 9521269
TI  - Neuronal metabolic dysfunction in patients with cortical developmental
      malformations: a proton magnetic resonance spectroscopic imaging study.
AB  - Cortical developmental malformations are best diagnosed by MRI and are often the
      cause of refractory epilepsy. Little is known about the metabolic cell function
      on MR spectroscopy of these types of brain anomaly. We studied 23 patients with
      cortical developmental malformations and refractory epilepsy using proton MR
      spectroscopic imaging. Mean age was 28 years (range, 9 to 47 years). The lesions
      examined were focal cortical dysplasia (n = 5), heterotopia (four band, six
      periventricular, two subcortical), polymicrogyria (n = 3), tuberous sclerosis (n
      = 2), and polymicrogyria and periventricular nodular heterotopia (n = 1). We
      measured the relative signal intensity of N-acetylaspartate/creatine (NAA/Cr) in
      the lesion, in the perilesional region, and in the region remote from the visible
      lesion. The values were compared with those from similar brain regions of 25
      normal control subjects. The mean NAA/Cr z score values for the 23 patients were
      as follows: lesion, -2.20 +/- 0.32 (mean +/- SE), n = 21; perilesional region, 
      1.01 +/- 0.38, n = 15; and distant region, -0.03 +/- 0.34, n = 18 (p < 0.0002).
      Despite the presence of a large number of neurons, heterotopia showed a relative
      decrease of NAA in some patients, suggesting that the neurons present were
      dysfunctional. The maximal NAA/Cr decrease, indicating metabolic dysfunction,
      colocalized to the structural malformation as defined by MRI and extended to
      normal-appearing regions adjacent to the visible lesion.

PMID- 9521270
TI  - PCR-based strategy for the diagnosis of hereditary neuropathy with liability to
      pressure palsies and Charcot-Marie-Tooth disease type 1A.
AB  - Charcot-Marie-Tooth disease type 1A (CMT1A) and hereditary neuropathy with
      liability to pressure palsies (HNPP) are inherited peripheral neuropathies. In
      most cases these disorders are caused by either the duplication (in CMT1A) or the
      deletion (in HNPP) of a 1.5-megabase DNA fragment on chromosome 17p11.2, which
      contains the peripheral myelin protein 22 gene (PMP22). We developed a rapid and
      simple quantitative PCR assay for the detection of the CMT1A duplication or the
      HNPP deletion. The assay is based on the quantitative determination of the copy
      number of a 240-base pair DNA fragment from exon 4 of the PMP22 gene.
      Quantification was done on an automated fluorescence sequencer. Using this method
      we analyzed four families with the HNPP phenotype. In these families we
      identified the deletion in all affected individuals. To test the validity of the
      method, we compared the quantitative PCR results from 50 DNA samples, including
      15 samples from individuals with HNPP, 15 samples from CMT1A patients, and 20
      from normal controls, with the results obtained by Southern blot analysis.
      Concordant results were obtained in 49 of the 50 cases.

PMID- 9521271
TI  - Paraneoplastic necrotizing myopathy: clinical and pathological features.
AB  - OBJECTIVE: To characterize the clinical features and muscle pathology of
      paraneoplastic necrotizing myopathy. BACKGROUND: Paraneoplastic syndromes
      involving many levels of the nervous system are well described, but there are
      only rare case reports of a necrotizing myopathy associated with cancer. DESIGN:
      Case series. RESULTS: We identified four patients with paraneoplastic necrotizing
      myopathy from muscle biopsies done at Washington University over a 10-year
      period. The patients (aged 38 to 76 years) presented with subacutely evolving,
      symmetric, proximal weakness. Tumor types included gastrointestinal
      adenocarcinoma (2 of 4), transitional cell carcinoma, prostatic carcinoma, and
      non-small cell lung carcinoma. Two patients died. Two others improved after
      treatment that included corticosteroids and tumor resection. Muscle pathology
      showed numerous necrotic fibers (8 to 100%) and intense alkaline phosphatase
      staining of the muscle connective tissue, but little inflammation. CONCLUSIONS:
      Paraneoplastic necrotizing myopathy is characterized by a rapidly progressive,
      symmetric, predominantly proximal weakness that produces severe disability.
      Muscle pathology demonstrates prominent necrosis with alkaline phosphatase
      staining of connective tissue and little inflammation. Evaluation for cancer is
      indicated in patients with these clinical and pathologic findings.

PMID- 9521272
TI  - Toward earlier diagnosis of amyotrophic lateral sclerosis: revised criteria.
      rhCNTF ALS Study Group.
AB  - We modified the World Federation of Neurology (WFN) diagnostic criteria for ALS
      to facilitate early diagnosis and used these criteria for enrollment of ALS
      patients in a clinical trial. The criteria developed required lower motor neuron
      (LMN) involvement in at least two limbs and upper motor neuron involvement in at
      least one region (bulbar, cervical, or lumbosacral). The EMG finding of
      fibrillation potentials was required for evidence of LMN involvement.
      Electrodiagnostic studies, neuroimaging, and laboratory studies were also used to
      exclude disorders that might mimic ALS. Using these criteria, the diagnosis of
      ALS was made at a mean time of 9.7 months from onset of symptoms, which compares
      favorably with the 12-month period cited in the literature. Using clinical
      assessment at completion of the trial, the diagnosis of ALS was believed to be
      accurate in those patients entered in the trial. However, pathologic confirmation
      of the diagnosis of ALS was not obtained. Based on our preliminary experience, we
      propose that these ALS diagnostic criteria will facilitate early diagnosis of
      ALS. Future studies should prospectively compare these criteria with the WFN
      criteria currently in use.

PMID- 9521273
TI  - The peripheral insulin-like growth factor system in amyotrophic lateral sclerosis
      and in multiple sclerosis.
AB  - A lack of trophic support may lead to degeneration of adult nerve cells. Several
      growth factors, including insulin-like growth factor I (IGF-I), control the
      survival of spinal motor neurons during development as well as after experimental
      injury. These neurons are selectively affected in patients with amyotrophic
      lateral sclerosis (ALS). Thus, we analyzed whether reduced levels of circulating
      IGF-I may be present in this disease. Significant increases were found in three
      of four of the main circulating IGF-binding proteins in ALS patients, whereas
      serum IGF-I and insulin levels were significantly reduced. On the contrary,
      multiple sclerosis patients did not show any significant change in the IGF-I
      trophic system even though oligodendrocytes are known targets of the trophic
      action of IGF-I. These results suggest an involvement of the peripheral IGF-I
      trophic system in ALS.

PMID- 9521274
TI  - Correlation between dynamic MRI and outcome in patients with malignant gliomas.
AB  - We assessed the correlation between dynamic MRI results and clinical outcomes in
      patients with malignant gliomas. Rapid serial MRIs were obtained after bolus
      injection of gadolinium that resulted in an initial fast uptake followed by a
      slow uptake of contrast. The maximum rate of uptake and delayed rate of uptake
      were correlated with survival and prognostic covariates such as age and
      histology. In 121 subjects, higher maximum uptake rates, 3.6 signal intensity
      units per second or greater, were associated with shorter survival (p = 0.0066).
      The correlation of delayed rate of uptake with survival was less significant.
      After adjusting for age, histology, and Karnofsky performance score, the maximum
      rate of uptake remained more significantly correlated with survival than the
      delayed rate of uptake. Thirty-one patients had surgery within 1 month of dynamic
      MRI, and those with glioblastoma multiforme or anaplastic gliomas had higher
      maximum rates of uptake than those with pure necrosis or mixed tumor and necrosis
      (p = 0.022). No correlation between delayed rate of uptake and histology was seen
      in this group of patients. Our results suggest that the maximum rate of uptake in
      dynamic MRI can be a prognostic measure for patients with malignant gliomas.
      Further prospective study is needed to assess the utility of this technique for
      evaluating brain tumors.

PMID- 9521275
TI  - Testosterone versus testosterone and testolactone in treating reproductive and
      sexual dysfunction in men with epilepsy and hypogonadism.
AB  - Antiepileptic drug-induced reductions in serum levels of biologically active
      testosterone and elevations in serum estradiol (E2) may contribute to sexual
      dysfunction among men with epilepsy. Treatment using a combination of
      testosterone and the aromatase inhibitor testolactone may have significantly
      better effects on sexual function and also seizure frequency than testosterone
      alone.

PMID- 9521276
TI  - Late-onset temporal lobe epilepsy and dilatation of the hippocampal sulcus by an
      enlarged Virchow-Robin space.
AB  - MRI signal changes within the hippocampal sulcus have been attributed to a
      dilated Virchow-Robin space within that sulcus, but no clinical correlates have
      previously been described. We present a 64-year-old man who developed right
      temporal seizures. MRI revealed an unusually enlarged Virchow-Robin space within
      the hippocampus, suggesting space-occupying effect. Such an abnormality should be
      considered a possible etiology in patients with late-onset temporal lobe
      epilepsy.

PMID- 9521277
TI  - Absence of normal activation of the left anterior fusiform gyrus during naming in
      left temporal lobe epilepsy.
AB  - Patients with left temporal lobe epilepsy (TLE) often have impaired naming. We
      studied 13 patients with left TLE and 10 healthy control subjects with [(15)O]H2O
      PET during visual confrontation naming. Statistical mapping detected multiple
      regions of significant cerebral blood flow increases within individuals. The left
      fusiform gyrus was activated in nine healthy subjects, but only in two patients
      with TLE (a significant difference, p < 0.001). Other activation sites were more
      variable in healthy subjects and those with TLE. Impaired naming ability may be
      associated with a lack of increased cerebral blood flow in the left fusiform
      gyrus in TLE.

PMID- 9521278
TI  - Epilepsy provoked by television and video games: safety of 100-Hz screens.
AB  - Television (TV) and video games (VG) can provoke seizures in patients with
      photosensitive epilepsies. Flicker frequency is the most important factor in
      screen activation. We tested conventional 50-Hz versus 100-Hz monitors during TV
      viewing and VG playing in 30 photosensitive subjects, 23 of whom had a history of
      TV or VG seizures or both. Fifteen subjects' discharges were activated by 50-Hz
      TV; 17 by 50-Hz VG; and one by a 100-Hz screen. Thus, 100-Hz screens protect
      against screen activation.

PMID- 9521279
TI  - Absorption, tolerability, and effects on mitochondrial activity of oral coenzyme
      Q10 in parkinsonian patients.
AB  - We report a pilot study of three oral doses of coenzyme Q10 (CoQ10) (200 mg
      administered two, three, or four times per day for 1 month) in 15 subjects with
      Parkinson's disease. Oral CoQ10 caused a substantial increase in the plasma CoQ10
      level. It was well tolerated, but at the highest dose (200 mg four times per day)
      mild, transient changes in the urine were noted. CoQ10 did not change the mean
      score on the motor portion of the Unified Parkinson's Disease Rating Scale. There
      was a trend toward an increase in complex I activity in the subjects.

PMID- 9521280
TI  - Reduction in voice tremor under thalamic stimulation.
AB  - We studied the effect of deep brain stimulation (DBS) of the ventral intermediate
      thalamic nucleus on voice symptoms in seven patients with essential tremor. All
      had undergone DBS for management of hand tremor. Five of the patients had
      received unilateral implants; two were treated bilaterally. Each reported
      improvement in hand tremor with thalamic stimulation (a 1-to-3-point change on a
      5-point severity scale). Voice tremor was evaluated with and without stimulation
      using patient and clinician severity ratings, and acoustic measures (rate and
      amplitude). Four of the seven patients showed reductions in voice symptoms in at
      least two of these measures, although degree of change differed (e.g., from 1 to
      3 points on the 5-point severity scale). Voice gains typically were restricted to
      those patients with the more severe symptoms and did not parallel improvements in
      the upper extremities. It appears that reduced voice tremor may be an additional
      benefit of DBS for some individuals.

PMID- 9521281
TI  - Genetic heterogeneity in autosomal recessive hereditary motor and sensory
      neuropathy with focally folded myelin sheaths (CMT4B).
AB  - Hereditary motor and sensory neuropathy with focally folded myelin sheaths, or
      Charcot-Marie-Tooth disease neuropathy type 4B (CMT4B), is a distinct clinical
      and genetic entity belonging to the heterogeneous group of autosomal recessive
      demyelinating neuropathies. We previously described a large pedigree with CMT4B
      and found evidence of linkage to chromosome 11q23. We now describe a second,
      unrelated family in which two individuals were affected with CMT4B. We exclude
      the disease locus segregating in this smaller pedigree from the 11q23 region as
      well as from most of the regions where other CMT loci have been mapped. We thus
      provide evidence for a second locus causing the CMT4B phenotype.

PMID- 9521282
TI  - Enhanced miotic response to topical dilute pilocarpine in patients with
      Alzheimer's disease.
AB  - To determine whether miotic response to dilute (0.0625%, two drops) topical
      pilocarpine could be useful in detecting Alzheimer's disease (AD), we assessed
      the response in 14 AD patients and 10 control subjects. The miotic response to
      pilocarpine was significantly greater in AD patients than in control subjects (p
      < 0.001). In contrast, mydriatic response to the anticholinergic tropicamide
      (0.01%, one drop) failed to show a difference between the groups (p = 0.54).
      There was no significant correlation between the miotic and mydriatic responses
      in individuals. We conclude that dilute pilocarpine could be useful as a
      diagnostic tool in early AD.

PMID- 9521283
TI  - Fluoroquinolone antibiotics block neuromuscular transmission.
AB  - Fluorinated 4-quinolones are widely used antibiotics. Several case reports
      describe the exacerbation of muscle weakness in myasthenia gravis patients
      treated with fluoroquinolones. We studied the effects of norfloxacin, ofloxacin,
      and pefloxacin on miniature endplate potentials (MEPPs) and currents. These
      antibiotics progressively decreased the amplitude of the MEPPs as drug
      concentrations were increased from 12.5 to 100 mg/L. Fluoroquinolones should be
      used only with great caution in disorders that compromise the safety margin of
      neuromuscular transmission.

PMID- 9521284
TI  - Sarcolemmal defect and subsarcolemmal lesion in a patient with gamma-sarcoglycan
      deficiency.
AB  - We report a case of gamma-sarcoglycanopathy with sarcolemmal defects and
      subsarcolemmal lesions indistinguishable from those in Duchenne muscular
      dystrophy. Both disorders share certain ultrastructure features that suggest a
      common pathogenesis related to primary deficiency of transmembrane glycoproteins
      (e.g., sarcoglycans) or deficiency in dystrophin, which produces a secondary
      deficiency in sarcoglycans. The lack of transmembrane glycoproteins may
      contribute to membrane lesions and associated muscle fiber degeneration and
      necrosis.

PMID- 9521285
TI  - Bilateral optic disk pallor after unilateral internal carotid artery occlusion.
AB  - Bilateral pallor of the optic disks was observed in a 52-year-old man after
      dissection of an internal carotid artery. Diffuse pallor of the ipsilateral optic
      disk reflected infarction of the ipsilateral optic nerve and "bow-tie" atrophy of
      the contralateral optic disk reflected infarction of the ipsilateral optic tract.
      The findings were due to an occlusion of the internal carotid artery proximal to
      the origin of the ophthalmic artery, resulting also in insufficiency in the area
      of supply of the anterior choroidal artery.

PMID- 9521286
TI  - Intracranial stenosis in Chinese patients with acute stroke.
AB  - We studied 100 consecutive acute stroke patients in a Chinese population with
      transcranial Doppler and CT. Twenty patients had intracerebral hemorrhage and 14
      patients did not have adequate temporal windows for transcranial Doppler
      examination. Among the remaining 66 patients, 22 patients (33%) had intracranial
      occlusive diseases and 3 (6%) had extracranial carotid stenosis. Our data showed
      that intracranial occlusive disease is the most commonly found vascular lesion in
      our acute stroke patients.

PMID- 9521287
TI  - Spontaneous dural carotid cavernous sinus fistula presenting isolated
      ophthalmoplegia: evaluation with MR angiography.
AB  - We describe three patients with spontaneous dural carotid cavernous sinus fistula
      presenting an isolated ophthalmoplegia where magnetic resonance angiography
      demonstrated abnormal flow-related enhancements in the cavernous sinus with
      extension into the inferior petrosal sinus. Magnetic resonance angiography is of
      value in evaluation of patients with isolated ophthalmoplegia.

PMID- 9521288
TI  - Neurologic manifestations of spinal epidural arteriovenous malformations.
AB  - Eight patients with spinal epidural arteriovenous malformations presented with
      progressive myelopathy (3), hemorrhage (3), and tinnitus/bruits (2). MRI
      suggested a vascular malformation in four (of seven) patients. Spinal angiography
      was necessary for diagnosis. Treatment by endovascular embolic occlusion (with
      balloons, particles, or coils) (7 patients) or surgical resection (4 patients),
      or both, temporarily arrested progression of neurologic symptoms, but recurrence
      of symptoms in two patients was associated with development of collateral
      arterial supply to the malformation.

PMID- 9521291
TI  - Isolated weakness of the fingers in cortical infarction.

PMID- 9521289
TI  - Chronic progressive leukoencephalopathy in adult celiac disease.
AB  - Progressive leukoencephalopathy developed in a patient with adult celiac disease.
      Neurologic abnormalities appeared 4 years after the gastrointestinal
      manifestations despite a gluten-free diet and replacement of vitamins. Brain MRI
      showed marked confluent white matter abnormalities, and stereotactic brain biopsy
      revealed chronic leukoencephalopathy. Treatment with I.V. steroids and
      immunoglobulins did not stop disease progression. Celiac disease should be
      considered in the differential diagnosis of the leukoencephalopathies.

PMID- 9521292
TI  - Procainamide-induced chronic inflammatory demyelinating polyradiculoneuropathy.

PMID- 9521290
TI  - Yawning as an aura for an L-dopa-induced "on" in Parkinson's disease.

PMID- 9521293
TI  - Neuropathic shoulder arthropathy (Charcot joint) associated with syringomyelia.

PMID- 9521294
TI  - The pathway of gustatory fibers of the human ascends ipsilaterally in the pons.

PMID- 9521295
TI  - Multiple intracranial and systemic aneurysms associated with infantile-onset
      arterial fibromuscular dysplasia.

PMID- 9521296
TI  - A bolt from the blue: lightning strike to the head.

PMID- 9521297
TI  - Cerebrospinal fluid creatine kinase BB isoenzyme activity and neurologic
      prognosis after cardiac arrest.

PMID- 9521298
TI  - "Gourmand syndrome".

PMID- 9521299
TI  - Pediatric migraine and the International Headache Society criteria.

PMID- 9521300
TI  - Non-epileptic seizures and depth recording.

PMID- 9521301
TI  - Improvement of stiff-man syndrome with vigabatrin.

PMID- 9521302
TI  - Albendazole therapy for neurocysticercosis.

PMID- 9521303
TI  - Albendazole therapy for neurocysticercosis.

PMID- 9521304
TI  - Could pure alexia be due to a disconnection syndrome?

PMID- 9521305
TI  - Lumboperitoneal shunting for pseudotumor cerebri.

PMID- 9521306
TI  - Cardiac cephalgia.

PMID- 9521307
TI  - Central poststroke pain associated with lateral medullary infarction.

PMID- 9521308
TI  - Competitiveness versus conferences?

PMID- 9521309
TI  - German Greens soften views on biotech as power edges closer.

PMID- 9521310
TI  - Decline in Indian publications raises alarm.

PMID- 9521311
TI  - Japan's genome programme goes ahead, with protein analysis.

PMID- 9521312
TI  - Some issues for the biosafety protocol.

PMID- 9521313
TI  - A pawn in a conspiracy?

PMID- 9521314
TI  - A checkpoint on the road to cancer.

PMID- 9521315
TI  - Malaria transmission. Has the ignition key been found?

PMID- 9521316
TI  - Visual processing. How to know where to go.

PMID- 9521317
TI  - Right on in sign language.

PMID- 9521318
TI  - Heartbeat synchronized with ventilation.

PMID- 9521319
TI  - Dendritic cells and the control of immunity.
AB  - B and T lymphocytes are the mediators of immunity, but their function is under
      the control of dendritic cells. Dendritic cells in the periphery capture and
      process antigens, express lymphocyte co-stimulatory molecules, migrate to
      lymphoid organs and secrete cytokines to initiate immune responses. They not only
      activate lymphocytes, they also tolerize T cells to antigens that are innate to
      the body (self-antigens), thereby minimizing autoimmune reactions. Once a
      neglected cell type, dendritic cells can now be readily obtained in sufficient
      quantities to allow molecular and cell biological analysis. With knowledge comes
      the realization that these cells are a powerful tool for manipulating the immune
      system.

PMID- 9521320
TI  - Total synthesis of brevetoxin A.
AB  - Brevetoxin A is the most potent neurotoxin secreted by Gymnodinium breve Davis, a
      marine organism often associated with harmful algal blooms known as 'red tides'.
      The compound, whose mechanism of action involves binding to and opening of sodium
      channels, is sufficiently toxic to kill fish at concentrations of nanograms per
      ml and, after accumulation in filter-feeding shellfish, to poison human
      consumers. The precise pathway by which nature constructs brevetoxin A is at
      present unknown, but strategies for its total synthesis have been contemplated
      for some time. The synthetic challenge posed by brevetoxin A reflects the high
      complexity of its molecular structure: 10 oxygen atoms and a chain of 44 carbon
      atoms are woven into a polycyclic macromolecule that includes 10 rings
      (containing between 5 and 9 atoms) and 22 stereogenic centres. Particularly
      challenging are the 7-, 8- and 9-membered rings which allow the molecule to
      undergo slow conformational changes and force a 90 degrees twist at one of its
      rings. Here we describe the successful incorporation of methods that were
      specifically developed for the construction of these rings into an overall
      strategy for the total synthesis of brevetoxin A in its naturally occurring form.
      The convergent synthesis reported here renders this scarce neurotoxin
      synthetically available and, more importantly, allows the design and synthesis of
      analogues for further biochemical studies.

PMID- 9521321
TI  - Common reference frame for neural coding of translational and rotational optic
      flow.
AB  - Self-movement of an organism through the environment is guided jointly by
      information provided by the vestibular system and by visual pathways that are
      specialized for detecting 'optic flow'. Motion of any object through space,
      including the self-motion of organisms, can be described with reference to six
      degrees of freedom: rotation about three orthogonal axes, and translation along
      these axes. Here we describe neurons in the pigeon brain that respond best to
      optic flow resulting from translation along one of the three orthogonal axes. We
      show that these translational optic flow neurons, like rotational optic flow
      neurons, share a common spatial frame of reference with the semicircular canals
      of the vestibular system. The three axes to which these neurons respond best are
      the vertical axis and two horizontal axes orientated at 45 degrees to either side
      of the body midline.

PMID- 9521322
TI  - Sniffing and smelling: separate subsystems in the human olfactory cortex.
AB  - The sensation and perception of smell (olfaction) are largely dependent on
      sniffing, which is an active stage of stimulus transport and therefore an
      integral component of mammalian olfaction. Electrophysiological data obtained
      from study of the hedgehog, rat, rabbit, dog and monkey indicate that sniffing
      (whether or not an odorant is present) induces an oscillation of activity in the
      olfactory bulb, driving the piriform cortex in the temporal lobe, in other words,
      the piriform is driven by the olfactory bulb at the frequency of sniffing. Here
      we use functional magnetic resonance imaging (fMRI) that is dependent on the
      level of oxygen in the blood to determine whether sniffing can induce activation
      in the piriform of humans, and whether this activation can be differentiated from
      activation induced by an odorant. We find that sniffing, whether odorant is
      present or absent, induces activation primarily in the piriform cortex of the
      temporal lobe and in the medial and posterior orbito-frontal gyri of the frontal
      lobe. The source of the sniff-induced activation is the somatosensory stimulation
      that is induced by air flow through the nostrils. In contrast, a smell,
      regardless of sniffing, induces activation mainly in the lateral and anterior
      orbito-frontal gyri of the frontal lobe. The dissociation between regions
      activated by olfactory exploration (sniffing) and regions activated by olfactory
      content (smell) shows a distinction in brain organization in terms of human
      olfaction.

PMID- 9521323
TI  - Nocistatin, a peptide that blocks nociceptin action in pain transmission.
AB  - Prolonged tissue damage or injury often leads to chronic pain states such that
      noxious stimuli evoke hyperalgesia and innocuous tactile stimuli evoke pain
      (allodynia). The neuropeptide nociceptin, also known as orphanin FQ, is an
      endogenous ligand for the orphan opioid-like receptor which induces both
      hyperalgesia and allodynia when administered by injection through the theca of
      the spinal cord into the subarachnoid space (that is, intrathecally). Here we
      show that the nociceptin precursor contains another biologically active peptide
      which we call nocistatin. Nocistatin blocks nociceptin-induced allodynia and
      hyperalgesia, and attenuates pain evoked by prostaglandin E2. It is the carboxy
      terminal hexapeptide of nocistatin (Glu-Gln-Lys-Gln-Leu-Gln), which is conserved
      in bovine, human and murine species, that possesses allodynia-blocking activity.
      We have also isolated endogenous nocistatin from bovine brain. Furthermore,
      intrathecal pretreatment with anti-nocistatin antibody decreases the threshold
      for nociceptin-induced allodynia. Although nocistatin does not bind to the
      nociceptin receptor, it binds to the membrane of mouse brain and of spinal cord
      with high affinity. Our results show that nocistatin is a new biologically active
      peptide produced from the same precursor as nociceptin and indicate that these
      two peptides may play opposite roles in pain transmission.

PMID- 9521324
TI  - Identification of xanthurenic acid as the putative inducer of malaria development
      in the mosquito.
AB  - Malaria is transmitted from vertebrate host to mosquito vector by mature sexual
      blood-living stages called gametocytes. Within seconds of ingestion into the
      mosquito bloodmeal, gametocytes undergo gametogenesis. Induction requires the
      simultaneous exposure to at least two stimuli in vitro: a drop in bloodmeal
      temperature to 5 degrees C below that of the vertebrate host, and a rise in pH
      from 7.4 to 8.0-8.2. In vivo the mosquito bloodmeal has a pH of between 7.5 and
      7.6. It is thought that in vivo the second inducer is an unknown mosquito-derived
      gametocyte-activating factor. Here we show that this factor is xanthurenic acid.
      We also show that low concentrations of xanthurenic acid can act together with pH
      to induce gametogenesis in vitro. Structurally related compounds are at least
      ninefold less effective at inducing gametogenesis in vitro. In Drosophila mutants
      with lesions in the kynurenine pathway of tryptophan metabolism (of which
      xanthurenic acid is a side product), no alternative active compound was detected
      in crude insect homogenates. These data could form the basis of the rational
      development of new methods of interrupting the transmission of malaria using
      drugs or new refractory mosquito genotypes to block parasite gametogenesis.

PMID- 9521325
TI  - Genetic basis and molecular mechanism for idiopathic ventricular fibrillation.
AB  - Ventricular fibrillation causes more than 300,000 sudden deaths each year in the
      USA alone. In approximately 5-12% of these cases, there are no demonstrable
      cardiac or non-cardiac causes to account for the episode, which is therefore
      classified as idiopathic ventricular fibrillation (IVF). A distinct group of IVF
      patients has been found to present with a characteristic electrocardiographic
      pattern. Because of the small size of most pedigrees and the high incidence of
      sudden death, however, molecular genetic studies of IVF have not yet been done.
      Because IVF causes cardiac rhythm disturbance, we investigated whether
      malfunction of ion channels could cause the disorder by studying mutations in the
      cardiac sodium channel gene SCN5A. We have now identified a missense mutation, a
      splice-donor mutation, and a frameshift mutation in the coding region of SCN5A in
      three IVF families. We show that sodium channels with the missense mutation
      recover from inactivation more rapidly than normal and that the frameshift
      mutation causes the sodium channel to be non-functional. Our results indicate
      that mutations in cardiac ion-channel genes contribute to the risk of developing
      IVF.

PMID- 9521326
TI  - Fas-mediated apoptosis and activation-induced T-cell proliferation are defective
      in mice lacking FADD/Mort1.
AB  - Programmed cell death, or apoptosis, is important in homeostasis of the immune
      system: for example, non-functional or autoreactive lymphocytes are eliminated
      through apoptosis. One member of the tumour necrosis factor receptor (TNFR)
      family, Fas (also known as CD95 or Apo-1), can trigger cell death and is
      essential for lymphocyte homeostasis. FADD/Mort1 is a Fas-associated protein that
      is thought to mediate apoptosis by recruiting the protease caspase-8. A dominant
      negative mutant of FADD inhibits apoptosis initiated by Fas and other TNFR family
      members. Other proteins, notably Daxx, also bind Fas and presumably mediate a
      FADD-independent apoptotic pathway. Here we investigate the role of FADD in vivo
      by generating FADD-deficient mice. As homozygous mice die in utero, we generated
      FADD-/- embryonic stem cells and FADD-/- chimaeras in a background devoid of the
      recombination activating gene RAG-1, which activates rearrangement of the
      immunoglobulin and T-cell receptor genes. We found that thymocyte subpopulations
      were apparently normal in newborn chimaeras. Fas-induced apoptosis was completely
      blocked, indicating that there are no redundant Fas apoptotic pathways. As these
      mice age, their thymocytes decrease to an undetectable level, although peripheral
      T cells are present in all older FADD-/- chimaeras. Unexpectedly, activation
      induced proliferation is impaired in these FADD-/- T cells, despite production of
      the cytokine interleukin (IL)-2. These results and the similarities between FADD
      /- mice and mice lacking the beta-subunit of the IL-2 receptor suggest that there
      is an unexpected connection between cell proliferation and apoptosis.

PMID- 9521327
TI  - Mutations of mitotic checkpoint genes in human cancers.
AB  - Genetic instability was one of the first characteristics to be postulated to
      underlie neoplasia. Such genetic instability occurs in two different forms. In a
      small fraction of colorectal and some other cancers, defective repair of
      mismatched bases results in an increased mutation rate at the nucleotide level
      and consequent widespread microsatellite instability. In most colorectal cancers,
      and probably in many other cancer types, a chromosomal instability (CIN) leading
      to an abnormal chromosome number (aneuploidy) is observed. The physiological and
      molecular bases of this pervasive abnormality are unknown. Here we show that CIN
      is consistently associated with the loss of function of a mitotic checkpoint.
      Moreover, in some cancers displaying CIN the loss of this checkpoint was
      associated with the mutational inactivation of a human homologue of the yeast
      BUB1 gene; BUB1 controls mitotic checkpoints and chromosome segregation in yeast.
      The normal mitotic checkpoints of cells displaying microsatellite instability
      become defective upon transfer of mutant hBUB1 alleles from either of two CIN
      cancers.

PMID- 9521328
TI  - Role of calcineurin and Mpk1 in regulating the onset of mitosis in budding yeast.
AB  - Signalling via calcium is probably involved in regulating eukaryotic cell
      proliferation, but details of its mechanism of action are unknown. In
      Schizosaccharomyces pombe, the onset of mitosis is determined by activation of a
      complex of the p34cdc2 protein kinase and a cyclin protein that is specific to
      the G2 phase of the cell cycle. This activation requires dephosphorylation of
      p34cdc2. Weel, a tyrosine kinase that inhibits p34cdc2 by phosphorylating it, is
      needed to determine the length of G2 phase. Here we show that calcium-activated
      pathways in Saccharomyces cerevisiae control the onset of mitosis by regulating
      Swel, a Weel homologue. Zds1 (also known as Oss1 and Hst1) is important in
      repressing the transcription of SWE1 in G2 phase. In the presence of high calcium
      levels, cells lacking Zds1 are delayed in entering mitosis. Calcineurin and Mpk1
      regulate Swel activation at the transcriptional and posttranslational levels,
      respectively, and both are required for the calcium-induced delay in G2 phase.
      These cellular pathways also induce a G2-phase delay in response to hypotonic
      shock.

PMID- 9521329
TI  - Human beta-tryptase is a ring-like tetramer with active sites facing a central
      pore.
AB  - Human tryptase, a mast-cell-specific serine proteinase that may be involved in
      causing asthma and other allergic and inflammatory disorders, is unique in two
      respects: it is enzymatically active only as a heparin-stabilized tetramer, and
      it is resistant to all known endogenous proteinase inhibitors. The 3-A crystal
      structure of human beta-tryptase in a complex with 4-amidinophenyl pyruvic acid
      shows four quasi-equivalent monomers arranged in a square flat ring of pseudo 222
      symmetry. Each monomer contacts its neighbours at two different interfaces
      through six loop segments. These loops are located around the active site of beta
      tryptase and differ considerably in length and conformation from loops of other
      trypsin-like proteinases. The four active centres of the tetramer are directed
      towards an oval central pore, restricting access for macromolecular substrates
      and enzyme inhibitors. Heparin chains might stabilize the complex by binding to
      an elongated patch of positively charged residues spanning two adjacent monomers.
      The nature of this unique tetrameric architecture explains many of tryptase's
      biochemical properties and provides a basis for the rational design of
      monofunctional and bifunctional tryptase inhibitors.

PMID- 9521330
TI  - Steps forward in the assessment of myocardial viability in left ventricular
      dysfunction.

PMID- 9521331
TI  - Heterogeneous immediate effects of partial left ventriculectomy on cardiac
      performance.
AB  - BACKGROUND: Partial left ventriculectomy (PLV) is a novel surgical treatment for
      severe heart failure consisting of resection of a large wedge of myocardium to
      reduce wall stress and restore the normal mass-volume ratio. Although ejection
      fraction (EF) has been shown to improve after PLV, few other physiological data
      describing its immediate effects on left ventricular (LV) performance are
      available. METHODS AND RESULTS: Eight patients, 58+/-5 years old, with severe
      clinical heart failure and EF of 12+/-3% were studied before and immediately
      after PLV. LV performance was assessed by the predominantly load-insensitive
      measures of pressure-area relations with high-fidelity pressure catheters and
      transesophageal automated echocardiographic measures of cross-sectional area as a
      surrogate for volume. LV end-diastolic volume decreased from 200+/-60 to 89+/-17
      mL, EF increased from 12+/-3% to 41+/-8%, and right ventricular (RV) fractional
      area change increased from 24+/-12% to 37+/-16% (all P<.05 versus before).
      Changes in pressure-area relations were variable: end-systolic elastance, 6.5+/
      3.4 to 4.3+/-2.5 mm Hg/cm2 and preload recruitable stroke work, 33+/-16 to 34+/
      19 mm Hg (P=NS versus before). End-diastolic stiffness increased from 0.13+/-0.06
      to 0.19+/-0.07 mm Hg/cm2 (P<.05 versus before). Improvement in LV performance was
      inversely correlated with semiquantitative histological assessment of myocardial
      fibrosis and positively correlated with nuclear enlargement and hyperchromasia,
      indicative of myocyte hypertrophy. No long-term follow-up data were available.
      CONCLUSIONS: PLV resulted in reductions in LV volumes, increases in EF and RV
      ejection, but increases in LV stiffness. Estimates of LV performance revealed
      variable results associated with the degree of myocardial fibrosis. Further study
      of these effects in relation to patient outcome is warranted.

PMID- 9521332
TI  - [18F]fluorodeoxyglucose single photon emission computed tomography: can it
      replace PET and thallium SPECT for the assessment of myocardial viability?
AB  - BACKGROUND: New high-energy collimators for single photon emission computed
      tomography (SPECT) cameras have made imaging of positron-emitting tracers, such
      as [18F]fluorodeoxyglucose (18FDG), possible. We examined differences between
      SPECT and PET technologies and between 18FDG and thallium tracers to determine
      whether 18FDG SPECT could be adopted for assessment of myocardial viability.
      METHODS AND RESULTS: Twenty-eight patients with chronic coronary artery disease
      (mean left ventricular ejection fraction [LVEF]=33+/-15% at rest) underwent 18FDG
      SPECT, 18FDG PET, and thallium SPECT studies. Receiver operating characteristic
      curves showed overall good concordance between SPECT and PET technologies and
      thallium and 18FDG tracers for assessing viability regardless of the level of
      18FDG PET cutoff used (40% to 60%). However, in the subgroup of patients with
      LVEF< or =25%, at 60% 18FDG PET threshold value, thallium tended to underestimate
      myocardial viability. In a subgroup of regions with severe asynergy, there were
      considerably more thallium/18FDG discordances in the inferior wall than elsewhere
      (73% versus 27%, P<.001), supporting attenuation of thallium as a potential
      explanation for the discordant observations. When uptake of 18FDG by SPECT and
      PET was compared in 137 segments exhibiting severely irreversible thallium
      defects (scarred by thallium), 59 (43%) were viable by 18FDG PET, of which 52
      (88%) were also viable by 18FDG SPECT. However, of the 78 segments confirmed to
      be nonviable by 18FDG PET, 57 (73%) were nonviable by 18FDG SPECT (P<.001).
      CONCLUSIONS: Although 18FDG SPECT significantly increases the sensitivity for
      detection of viable myocardium in tissue declared nonviable by thallium (to 88%
      of the sensitivity achievable by PET), it will occasionally (27% of the time)
      result in falsely identifying as viable tissue that has been identified as
      nonviable by both PET and thallium.

PMID- 9521333
TI  - Selective defect in nitric oxide synthesis may explain the impaired endothelium
      dependent vasodilation in patients with essential hypertension.
AB  - BACKGROUND: Patients with essential hypertension have impaired endothelial NO
      activity, but the mechanism underlying this abnormality is unknown. METHODS AND
      RESULTS: To investigate whether the endothelial dysfunction of hypertensive
      patients is related to a selective defect in NO synthesis, we studied the forearm
      blood flow responses to intra-arterial infusion of acetylcholine (7.5 to 30
      microg/min), an endothelial agonist linked to NO synthase through the Ca2+
      signaling pathway, and isoproterenol (50 to 200 ng/min), a beta-adrenoceptor
      agonist that stimulates NO production by increasing intracellular cAMP, in 12
      normotensive subjects and 12 hypertensive patients. The infusion of isoproterenol
      was repeated during the concurrent blockade of NO synthesis by NG-monomethyl-L
      arginine (L-NMMA; 4 micromol/min). The vasodilator response to acetylcholine was
      significantly reduced in hypertensives compared with normotensives (maximum blood
      flow: 10.4+/-4.6 versus 14.4+/-3.7 mL x min[-1] x dL[-1]; P=.008). However, the
      vasodilator effect of isoproterenol was similar in normotensives and
      hypertensives (maximum blood flow: 14.4+/-5.4 versus 13.5+/-5 mL x min[-1] x dL[
      1]; P=.56) and was significantly (both P<.01) and equally blunted by L-NMMA in
      both groups (maximum blood flow: 11+/-3 mL x min[-1] x dL[-1] in normotensives
      versus 10.8+/-3.9 mL x min[-1] x dL[-1] in hypertensives; P=.77). The vasodilator
      response to sodium nitroprusside (0.8 to 3.2 microg/min), an exogenous NO donor,
      was similar in both groups and was not modified by L-NMMA. CONCLUSIONS:
      Hypertensive patients have impaired endothelium-dependent vasodilation in
      response to acetylcholine but preserved NO activity in response to beta
      adrenergic stimulation. These findings suggest that the endothelial dysfunction
      in essential hypertension is due to a selective abnormality of NO synthesis,
      probably related to a defect in the phosphatidylinositol/Ca2+ signaling pathway.

PMID- 9521335
TI  - Relationships of abdominal obesity and hyperinsulinemia to angiographically
      assessed coronary artery disease in men with known mutations in the LDL receptor
      gene.
AB  - BACKGROUND: Patients with a mutation in the LDL receptor gene (familial
      hypercholesterolemia, or FH) are characterized by substantial elevations in
      plasma LDL cholesterol and are at higher risk of developing coronary artery
      disease (CAD). Correlates of abdominal obesity may also contribute to the risk of
      ischemic cardiac events. Whether the hyperinsulinemic-insulin-resistant state of
      abdominal obesity affects coronary atherosclerosis among FH patients has not been
      determined. METHODS AND RESULTS: The relation of abdominal adiposity and
      hyperinsulinemia to angiographically assessed CAD was evaluated in a sample of
      120 French Canadian men aged <60 years who were heterozygotes for FH and in a
      group of 280 men without FH. In the present study, the risk of CAD associated
      with abdominal obesity, as estimated by the waist circumference, was largely
      dependent on the concomitant variation in plasma lipoprotein and insulin
      concentrations. In contrast, the association between fasting insulin and CAD was
      independent of variations in waist girth, triglyceride, HDL, and apolipoprotein B
      concentrations (odds ratio, 1.86; P=.0005). However, the most substantial
      increase in the risk of CAD was observed among abdominally obese (waist
      circumference >95 cm) and hyperinsulinemic FH patients (odds ratio, 12.9;
      P=.0009). This increase in risk remained significant even after adjustment for
      LDL cholesterol or apolipoprotein B concentrations. CONCLUSIONS: Results of the
      present study provide support for the notion that the hyperinsulinemic-insulin
      resistant state of abdominal obesity is a powerful predictor of CAD in men, even
      in a group of patients with raised LDL cholesterol concentrations due to FH.

PMID- 9521334
TI  - Abciximab therapy and unplanned coronary stent deployment: favorable effects on
      stent use, clinical outcomes, and bleeding complications. EPILOG Trial
      Investigators.
AB  - BACKGROUND: The clinical and angiographic demographics of patients requiring
      unplanned coronary stent deployment and the optimal adjunct pharmacotherapy in
      this population are not well described. This report details the EPILOG trial
      experience with unplanned coronary stent deployment and the effect of abciximab
      platelet glycoprotein IIb/IIIa blockade to improve clinical outcomes during 6
      months of follow-up. METHODS AND RESULTS: After randomization in the EPILOG
      double-blind, placebo-controlled trial of abciximab therapy during percutaneous
      coronary intervention, 326 (12%) of 2792 patients required unplanned coronary
      stent deployment. Although stented patients were not distinguished by clinical
      variables, they had greater coronary lesion complexity by American Heart
      Association/American College of Cardiology criteria (P=.003) and greater
      incidence of lesion length >10 mm (P=.002), lesion eccentricity (P=.027),
      irregular lesion contour (P=.001), and bifurcation involvement (P=.019) than
      nonstented patients. Unplanned stents were required less often in patients
      treated with abciximab and low-dose, weight-adjusted heparin than in patients
      receiving placebo and standard-dose heparin (9.0% versus 13.7%; P=.001). Although
      adverse clinical outcomes including target-vessel revascularization and bleeding
      events were more frequent in patients requiring unplanned coronary stent
      deployment, abciximab therapy reduced adverse outcomes in these patients at 30
      days and 6 months to a greater extent than was observed in patients not requiring
      stent placement. Among stented patients, abciximab therapy did not increase
      bleeding events. CONCLUSIONS: Patients requiring unplanned coronary stent
      deployment have more complex coronary lesion morphology and a more complicated
      clinical course after coronary intervention. Abciximab therapy both reduces the
      need for unplanned stent deployment and confers clinical benefit to patients
      requiring an unplanned stent, without increasing bleeding complications.

PMID- 9521336
TI  - Histopathology of human coronary atherosclerosis by quantifying its chemical
      composition with Raman spectroscopy.
AB  - BACKGROUND: Lesion composition, rather than size or volume, determines whether an
      atherosclerotic plaque will progress, regress, or rupture, but current techniques
      cannot provide precise quantitative information about lesion composition. We have
      developed a technique to assess the pathological state of human coronary artery
      samples by quantifying their chemical composition with near-infrared Raman
      spectroscopy. METHODS AND RESULTS: Coronary artery samples (n=165) obtained from
      explanted recipient hearts were illuminated with 830-nm infrared light. Raman
      spectra were collected from the tissue and processed to quantify the relative
      weights of cholesterol, cholesterol esters, triglycerides and phospholipids, and
      calcium salts in the examined artery location. The artery locations were then
      classified by a pathologist and grouped as either nonatherosclerotic tissue,
      noncalcified plaque, or calcified plaque. Nonatherosclerotic tissue, which
      included normal artery and intimal fibroplasia, contained an average of
      approximately 4+/-3% cholesterol, whereas noncalcified plaques had approximately
      26+/-10% and calcified plaques approximately 19+/-10% cholesterol in the
      noncalcified regions. The average relative weight of calcium salts was 1+/-2% in
      noncalcified plaques and 41+/-21% in calcified plaques. To make this quantitative
      chemical information clinically useful, we developed a diagnostic algorithm,
      based on a first set of 97 samples, that demonstrated a strong correlation of the
      relative weights of cholesterol and calcium salts with histological diagnoses of
      the same locations. This algorithm was then prospectively tested on a second set
      of 68 samples. The algorithm correctly classified 64 of these new samples, thus
      demonstrating the accuracy and robustness of the method. CONCLUSIONS: The
      pathological state of a given human coronary artery may be assessed by
      quantifying its chemical composition, which can be done rapidly with Raman
      spectroscopic techniques. When Raman spectra are obtained clinically via optical
      fibers, Raman spectroscopy may be useful in monitoring the progression and
      regression of atherosclerosis, predicting plaque rupture, and selecting proper
      therapeutic intervention.

PMID- 9521337
TI  - Randomized, double-blind, placebo-controlled study of ascorbate on the preventive
      effect of nitrate tolerance in patients with congestive heart failure.
AB  - BACKGROUND: Reduced cGMP production caused by increased superoxide has been
      proposed as a mechanism of nitrate tolerance during continuous nitrate therapy.
      This study was designed to evaluate the effects of ascorbate, an antioxidant, on
      the development of nitrate tolerance during continuous nitrate therapy in
      patients with congestive heart failure. METHODS AND RESULTS: Twenty patients with
      congestive heart failure were randomized to receive intravenous infusion of
      nitroglycerin concomitantly with placebo (placebo group, n=10) or intravenous
      ascorbate (vitamin C group, n=10). After baseline measurements were obtained,
      dose titration was started by the infusion of nitroglycerin at a rate of 0.5
      microg/kg per minute (titration period). Measurements of hemodynamic parameters
      and blood sampling were performed serially at 0, 6, 12, 18, and 24 hours after
      the titration period. At baseline, mean pulmonary artery pressure (MPAP, mm Hg),
      mean pulmonary capillary wedge pressure (PCWP, mm Hg), plasma vitamin E level
      (micromol/L), and platelet cGMP level (pmol/10[9] platelets) were comparable in
      the two groups (placebo group: MPAP, 48+/-6; PCWP, 24+/-4; cGMP, 0.76+/-0.12;
      vitamin E, 18.2+/-1.2; vitamin C: MPAP, 49+/-7; PCWP, 24+/-4; cGMP, 0.71+/-0.16;
      vitamin E, 18.6+/-1.3). In both groups, at 6 hours after the titration period,
      MPAP and PCWP were significantly decreased (placebo group: MPAP, 26+/-5; PCWP,
      15+/-4; vitamin C: MPAP, 26+/-4; PCWP, 16+/-4), and platelet cGMP was
      significantly increased (placebo group: 2.42+/-0.24; vitamin C: 2.26+/-0.26).
      However, at 18 hours after titration, in the placebo group, MPAP (44+/-5) and
      PCWP (23+/-4) were increased, and platelet cGMP (0.85+/-0.20) and plasma vitamin
      E levels (12.4+/-1.4) were significantly decreased. In contrast, in the vitamin C
      group, MPAP (31+/-6), PCWP (17+/-5), platelet cGMP (2.49+/-0.23), and plasma
      vitamin E levels (17.6+/-1.4) were maintained for 18 hours after the titration
      period. CONCLUSIONS: These findings indicate that ascorbate, an antioxidant, may
      prevent the development of nitrate tolerance during continuous nitrate therapy in
      patients with congestive heart failure.

PMID- 9521338
TI  - Expression of Gq alpha and PLC-beta in scar and border tissue in heart failure
      due to myocardial infarction.
AB  - BACKGROUND: Large transmural myocardial infarction (MI) leads to maladaptive
      cardiac remodeling and places patients at increased risk of congestive heart
      failure. Angiotensin II, endothelin, and alpha1-adrenergic receptor agonists are
      implicated in the development of cardiac hypertrophy, interstitial fibrosis, and
      heart failure after MI. Because these agonists are coupled to and activate Gq
      alpha protein in the heart, the aim of the present study was to investigate Gq
      alpha expression and function in cardiac remodeling and heart failure after MI.
      METHODS AND RESULTS: MI was produced in rats by ligation of the left coronary
      artery, and Gq alpha protein concentration, localization, and mRNA abundance were
      noted in surviving left ventricle remote from the infarct and in border and scar
      tissues from 8-week post-MI hearts with moderate heart failure.
      Immunohistochemical staining localized elevated Gq alpha expression in the scar
      and border tissues. Western analysis confirmed significant upregulation of Gq
      alpha proteins in these regions versus controls. Furthermore, Northern analysis
      revealed that the ratios of Gq alpha/GAPDH mRNA abundance in both scar and viable
      tissues from experimental hearts were significantly increased versus controls.
      Increased expression of phospholipase C (PLC)-beta1 and PLC-beta3 proteins was
      apparent in the scar and viable tissues after MI versus controls and is
      associated with increased PLC-beta1 activity in experimental hearts. Furthermore,
      inositol 1,4,5-tris-phosphate is significantly increased in the border and scar
      tissues compared with control values. CONCLUSIONS: Upregulation of the Gq
      alpha/PLC-beta pathway was observed in the viable, border, and scar tissues in
      post-MI hearts. Gq alpha and PLC-beta may play important roles in scar remodeling
      as well as cardiac hypertrophy and fibrosis of the surviving tissue in post-MI
      rat heart. It is suggested that the Gq alpha/PLC-beta pathway may provide a
      possible novel target for altering postinfarct remodeling.

PMID- 9521339
TI  - Differential effects of anti-beta2-glycoprotein I antibodies on endothelial cells
      and on the manifestations of experimental antiphospholipid syndrome.
AB  - BACKGROUND: The antiphospholipid syndrome (APS) entails a prothrombotic state
      associated with the presence of anticardiolipin antibodies (aCL). aCL were shown
      to promote endothelial cell and platelet activation and to induce an APS-like
      syndrome in mice when administered intravenously. Recent data suggest that aCL
      target the plasma cofactor beta2-glycoprotein I (beta2GPI) rather than negatively
      charged phospholipids. However, it has not been determined whether different
      epitope-specific anti-beta2GPI antibodies obtained from one patient possess
      pathogenic properties. METHODS AND RESULTS: Three beta2GPI-binding IgM monoclonal
      antibodies (mAbs) (ILA-1, ILA-3, and ILA-4) were cloned from a patient with APS.
      The three antibodies were shown to bind beta2GPI immobilized on irradiated
      plates, yet only ILA-1 bound beta2GPI coated onto nonirradiated plates.
      Furthermore, when using the anti-beta2GPI enzyme-linked immunosorbent assay, ILA
      1 was the only mAb inhibited by fluid phase beta2GPI. ILA-1 and ILA-3, but not
      ILA-4, induced adherence of U937 cells to endothelial cells in vitro (reflecting
      activation of endothelial cells). mAbs ILA-1 and ILA-3 as opposed to ILA-4
      induced significant expression of adhesion molecules when preincubated with human
      umbilical vein endothelial cells. Passive administration of ILA-1 and ILA-3 to
      pregnant BALB/c mice induced clinical findings consistent with APS (increased
      fetal resorptions, reduced platelet counts, and prolonged activated partial
      thromboplastin time), whereas both ILA-4 and the control human IgM did not
      produce similar effects. CONCLUSIONS: The results of the study demonstrate the
      differential effects of various populations of anti-beta2GPI antibodies on
      endothelial cell activation and on experimental APS.

PMID- 9521341
TI  - Aortocoronary saphenous vein graft disease: pathogenesis, predisposition, and
      prevention.
AB  - Aortocoronary saphenous vein graft disease, with its increasing clinical
      sequelae, presents an important and unresolved dilemma in cardiological practice.
      During the 1st month after bypass surgery, vein graft attrition results from
      thrombotic occlusion, while later the dominant process is atherosclerotic
      obstruction occurring on a foundation of neointimal hyperplasia. Although the
      risk factors predisposing to vein graft atherosclerosis are broadly similar to
      those recognized for native coronary disease, the pathogenic effects of these
      risk factors are amplified by inherent deficiencies of the vein as a conduit when
      transposed into the coronary arterial circulation. A multifaceted strategy aimed
      at prevention of vein graft disease is emerging, elements of which include:
      continued improvements in surgical technique; more effective antiplatelet drugs;
      increasingly intensive risk factor modification, in particular early and
      aggressive lipid-lowering drug therapy; and a number of evolving therapies, such
      as gene transfer and nitric oxide donor administration, which target vein graft
      disease at an early and fundamental level. At present, a key measure is to
      circumvent the problem of vein graft disease by preferential selection of
      arterial conduits, in particular the internal mammary arteries, for coronary
      bypass surgery whenever possible.

PMID- 9521340
TI  - Beta3 integrins are upregulated after vascular injury and modulate thrombospondin
      and thrombin-induced proliferation of cultured smooth muscle cells.
AB  - BACKGROUND: Treatment with an antibody that binds beta3 integrins (abciximab;
      c7E3 Fab) at the time of coronary angioplasty decreases the need for repeat
      revascularization. Two potential mechanisms have been proposed to explain this
      effect: (1) inhibition of platelet aggregation or (2) interruption of ligand
      binding to beta3 integrins on the smooth muscle cell (SMC) surface. We examined
      the latter hypothesis by determining (1) if beta3 integrin expression is
      upregulated after vascular injury in the baboon, (2) if 7E3 binds beta3 integrins
      on cultured SMC, and (3) if beta3 integrin activation plays a role in
      proliferation of cultured SMC. METHODS AND RESULTS: Results demonstrated that
      immunostaining for beta3 integrins was present in the neointima 1 week after
      balloon withdrawal injury of baboon brachial arteries and that beta3 integrin
      expression colocalized with alpha-actin-positive cells. In contrast, staining for
      beta3 integrins was undetectable in contralateral uninjured brachial arteries.
      7E3 bound to cultured human aortic SMC with an affinity (KD=3.3 nmol/L) similar
      to 7E3 binding to endothelial cells or platelets. Cotreatment with 7E3 partially
      inhibited thrombospondin-induced or alpha-thrombin-induced proliferation but not
      PDGF-induced or serum-induced proliferation. CONCLUSIONS: In summary, these
      studies demonstrate that vascular cell beta3 integrin expression is increased
      after injury, that 7E3 binds to cultured SMC with high affinity, and that beta3
      activation is important for thrombospondin-induced or alpha-thrombin-induced
      proliferation. These results support the hypothesis that beta3 integrins play a
      role in SMC growth responses after balloon injury.

PMID- 9521342
TI  - Images in cardiovascular medicine. Late sequelae of traumatic aortic rupture.

PMID- 9521343
TI  - Images in cardiovascular medicine. Connective tissue skeleton of the human heart:
      a demonstration by cell-maceration scanning electron microscope method.

PMID- 9521344
TI  - Small, dense LDL particles and coagulation.

PMID- 9521345
TI  - Does 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor therapy exert a
      direct anti-ischemic effect?

PMID- 9521346
TI  - Increased vagal activity in idiopathic VF.

PMID- 9521347
TI  - Echocardiographic effects of prostacyclin?

PMID- 9521348
TI  - Major depression: behavioral markers of depression and recovery.
AB  - The concepts of psychosocial and psychomotor inhibition characteristic of major
      depression are based primarily on clinical observations. It is possible to
      describe and define these two types of inhibition by means of a systematic,
      quantitative ethological (behavioral) approach, which singles out precise and
      significant behavior markers. This investigation focuses on the behavioral
      features of psychosocial and psychomotor inhibition in 11 hospitalized depressed
      subjects and their changes during clinical recovery. The hypothesis that major
      depression is characterized by a significant reduction of social interaction is
      tested (psycho-intellectual inhibition is not addressed). Results show
      significant behavioral differences between depressed and recovered subjects with
      depression being characterized by a significant reduction of social interaction,
      whereas self occupation and body mobility are reduced to a lesser degree.
      Behavior markers for depression include nonspecific gaze, withdrawal, no mouth
      movements, no eye region movements, and social inactivity. Behavior markers for
      recovery include socially interested, social smile, verbal social initiative,
      speech, nod, raised eyebrows, wrinkled eyebrows, social laughter, gesticulation,
      drum one's fingers, point, and help. Findings point to tendencies toward two
      types of major depression and two types of recovery. A companion paper (Schelde,
      this journal) addresses theoretical issues.

PMID- 9521349
TI  - Major depression: behavioral parameters of depression and recovery.
AB  - This paper reports on an ethological study of 11 depressed hospitalized subjects.
      Major depression and recovery are described in terms of general behavioral
      traits, i.e., behavior parameters. The hypothesis, that the primary behavioral
      feature of major depression is a reduction of social interaction and that
      secondary features are reduced self occupation and body mobility (posture
      flexibility) is tested. The behavioral patterns of depression and recovery are
      described and elucidated by 12 defined behavioral parameters, eight of which show
      significant changes between the first and the last hospital week. Findings from
      six of the parameters are consistent with the hypothesis and demonstrate social
      inhibition during depression; interactions between depression and nonverbal
      behavior are particularly striking. Findings also confirm that, during
      depression, self occupation and body mobility are reduced to a less significant
      degree than social inhibition. Possible relationships between findings and
      agitated forms of major depression are discussed. A final section examines
      findings in an evolutionary context and emphasizes their clinical implications.

PMID- 9521350
TI  - Obsessions and compulsions as a distinct cluster of symptoms in schizophrenia: a
      neuropsychological study.
AB  - Using neurocognitive testing, the present study assessed whether obsessions and
      compulsions could represent a distinct cluster of symptoms in schizophrenia. We
      formulated our hypothesis based on data from nonschizophrenic patients, expecting
      to find that schizophrenic patients with obsessive-compulsive (OC) symptoms would
      experience more difficulties in the same cognitive areas as nonschizophrenic
      patients with obsessive-compulsive disorder (OCD). Patients had separate
      psychiatric and cognitive evaluations. The OC and non-OC schizophrenic subjects
      did not differ significantly on the positive and negative symptom scores.
      However, compared with non-OC schizophrenic patients, those with OC symptoms
      performed worse on cognitive areas thought to be impaired (i.e., visual-spatial
      skills, delayed nonverbal memory, and cognitive shifting abilities). In addition,
      the severity of OC scores correlated with poor performance in these areas of
      cognition. Our results support our hypothesis, specifically that OC symptoms may
      constitute a distinct cluster separate from psychosis in schizophrenia and raise
      the possibility of a distinct subtype of schizophrenia. The theoretical and
      clinical implications of these findings are discussed.

PMID- 9521351
TI  - Impulsive and compulsive self-injurious behavior in bulimia nervosa: prevalence
      and psychological correlates.
AB  - A specific link between self-injurious behavior and bulimia nervosa has been
      observed. In affective spectrum disorders, some authors propose a distinction
      between impulsive and compulsive self-injurious behavior. One of the aims of the
      present study is to examine how different kinds of self-injurious behavior,
      including purging behavior, may be classified in bulimia nervosa. The clinical
      impact of the different types of self-injury will be studied. The subjects of the
      study were 125 consecutive patients with bulimia nervosa, diagnosed by DSM-IV
      criteria. Subjects were evaluated by means of a semistructured interview and self
      report questionnaires (Eating Disorders Inventory and Hopkins Symptom Checklist).
      In our sample, the distinction between compulsive and impulsive self-injurious
      behavior appeared to be confirmed by a principal component analysis. Self-induced
      vomiting loaded on the compulsive dimension and laxative abuse on the impulsive
      dimension. To study the clinical impact of the two kinds of behavior, bulimic
      subjects were divided according to their position in the two dimensions. The
      presence of impulsive self-injurious behavior is associated with a history of
      sexual abuse and with higher scores on the Symptom Checklist. The presence of
      both impulsive and compulsive behavior is associated with greater depression,
      whereas the presence of impulsive features in the absence of compulsive ones
      seems to be linked to a longer duration of illness and to a higher dropout rate.
      Both compulsive and impulsive self-injurious behaviors are associated with a
      greater lack of interoceptive awareness.

PMID- 9521352
TI  - Preliminary evidence of psychological distress among reservists in the Persian
      Gulf War.
AB  - This study was conducted as a preliminary investigation into the presence and
      nature of psychological distress among military reserve personnel as a result of
      their participation in the Persian Gulf War. Eleven months after cessation of
      hostilities in the Gulf War, a self-report survey was mailed to the home of each
      of the 1090 members who had been assigned to the study Air National Guard unit
      during this period. After unit activation in December 1990, 517 of these
      individuals were deployed to the Persian Gulf as participants in Operation Desert
      Storm. The remainder of the unit participated in their military service during
      this period without being deployed to the Persian Gulf. The survey consisted of a
      demographic section, the Mississippi Scale for Combat Related Posttraumatic
      Stress Disorder (M-PTSD), the revised Symptom Checklist 90 (SCL-90-R), and an
      anecdotal response section; 46% of those surveyed responded. The major finding of
      the study was that 6.8% of the respondents who served in the combat theater had
      elevated M-PTSD scores. This was a statistically significant finding compared
      with the 1.7% of those surveyed who had elevated M-PTSD scores having served at
      home (chi2 = 6.25, df = 1, p = .01). These elevated M-PTSD scores were found
      despite low levels of traditional combat stressors and strong levels of perceived
      public support. SCL-90-R scores were also higher in deployed versus nondeployed
      respondents. Although the clinical presence of PTSD was not established by this
      study, the preliminary finding of elevated M-PTSD scores in the deployed group is
      suggestive of the possibility of clinical PTSD. This finding supports the need
      for further PTSD research among reservists who are exposed to nontraditional
      combat stressors. Elevated SCL-90-R scores in the deployed group also suggest
      that other forms of psychological distress may have developed in a significant
      number of combat veterans of the Persian Gulf War.

PMID- 9521353
TI  - An eighteen-year follow-up study of Israeli prisoners of war and combat veterans.
AB  - The current study assesses the psychological and psychiatric aftermath of war
      captivity; 164 Israeli ex-POWs and 189 comparable controls were assessed for
      posttraumatic stress disorder, intrusion and avoidance tendencies, and
      generalized psychiatric symptomatology 18 years after the war. Findings indicated
      that trauma-related psychopathology and general psychiatric symptomatology were
      more prevalent among POWs than among their matched controls. In addition,
      captivity experience, social support at homecoming, and, above all,
      sociodemographic and military factors were found to be strongly correlated with
      the outcome measures. Theoretical and clinical implications of the aftermath of
      captivity are discussed.

PMID- 9521354
TI  - Delayed neuropsychiatric effects of malaria in Ghana.
AB  - This study investigated the long-term emotional and cognitive effects of malaria
      infection in a sample of community resident nonmigratory Ghanaian adults,
      comparing 142 individuals with a documented history of clinical falciparum
      malaria and 30 controls without a lifetime medical diagnosis of malaria. Results
      were based on self-report inventory and interview-based approaches to assessment
      of emotional status as well as individual administration of the Mini-Mental State
      Examination. Our findings indicated the presence of an enduring, albeit
      subclinical, mixed anxiety-depression syndrome after medical recovery from
      falciparum malaria. There were, however, no significant neurocognitive deficits
      associated with malaria status on the objective screening instrument, nor were
      there reports of subjective attention, concentration, memory, or other cognitive
      complaints by self-report. Malaria may be a risk factor for psychiatric
      morbidity. We therefore recommend a search for effective malaria prevention and
      intervention strategies to avert the more serious clinical manifestations of
      mental disorder likely to evolve in this imminently lethal infectious disease.

PMID- 9521355
TI  - A systematic review of research on religion in four major psychiatric journals:
      1991-1995.

PMID- 9521356
TI  - Risk indicators for the Charles Bonnet syndrome.

PMID- 9521358
TI  - The erythrocyte sedimentation rate: old and new clinical applications.
AB  - BACKGROUND: The erythrocyte sedimentation rate (ESR) is a simple and inexpensive
      laboratory test. It is commonly used to assess the acute phase response. METHODS:
      A review of the recent literature was done to evaluate the role of the ESR and
      its importance in different clinical conditions both inflammatory and
      noninflammatory. RESULTS: Despite the critical role cytokines have in
      inflammatory conditions, the ESR still maintains its important role in the
      diagnosis and follow-up of rheumatoid arthritis and temporal arteritis. Recently,
      ESR has been reported to be of clinical significance in sickle cell disease,
      osteomyelitis, and, surprisingly, in noninflammatory conditions such as stroke,
      coronary artery disease, and prostate cancer. Erythrocyte sedimentation rate
      measured by the Westergren method is marginally affected by age, race, and blood
      storage. CONCLUSION: Despite its importance in many clinical conditions, ESR
      should be used only as a clinical guide to aid the diagnosis, management, and
      follow-up of these different clinical situations.

PMID- 9521357
TI  - Musical hallucinations induced by propranolol.

PMID- 9521359
TI  - Medical practices of past graduates from one obstetric/gynecologic training
      program.
AB  - BACKGROUND: We sought to assess the practice patterns of former obstetric
      gynecologic residents and to solicit their opinions regarding their educational
      experience and its clinical relevance to primary care. METHOD: In response to a
      Residency Review Committee mandate regarding past residents, a questionnaire was
      sent to all graduates from our residency program over a 17-year period (1979 to
      1995). RESULTS: Of the 90 subjects who received the survey, 86 responded. Their
      ages ranged from 29 years to 49 years; 79 were married and 7 were single. Of the
      75 in clinical practice, 71 practiced both obstetrics and gynecology and 13 had
      subspecialized. Most of the respondents (77/80) practiced in the mid-South. Of
      all graduates, 93% routinely provided primary care. In rating 20 major resident
      education categories, respondents gave high grades to training in surgically
      related areas. Only 4% rated their experience as fair or poor in the operative
      categories. CONCLUSION: Our graduates indicate satisfaction with their training,
      and their practices include primary care.

PMID- 9521360
TI  - Formal pathology rotation during obstetrics and gynecology residency: is it
      beneficial?
AB  - BACKGROUND: Our objective was to assess the educational benefits of a formal
      pathology rotation during an obstetrics and gynecology residency program and to
      determine the utility of this information in clinical practice. METHODS: In this
      descriptive study, the benefits of a 2-month rotation in pathology for obstetrics
      and gynecology residents were analyzed. A computerized listing of surgical cases
      processed by each resident was sent to the obstetrics and gynecology program
      director. RESULTS: Our resident accessioned 5.4% of the total pathology cases
      processed each month. Reports from previous residents (over a 17-year period) and
      from program directors at the annual educational retreat indicate that such
      information was not relevant to our graduates in their clinical practice.
      CONCLUSIONS: A formal pathology rotation for obstetric residents can improve
      knowledge base, but the usefulness of this knowledge in clinical practice is
      dubious.

PMID- 9521361
TI  - Are newspapers a viable source for intentional injury surveillance data?
AB  - BACKGROUND: Previous researchers have reported that newspapers were useful
      adjuncts to unintentional injury surveillance efforts in a nearby southern state.
      The current study sought to determine whether newspaper accounts of intentional
      injuries could provide a reliable source of primary or secondary surveillance
      data. METHODS: Newspaper accounts of assaults, homicides, suicides, and rapes
      occurring in Jefferson County, Alabama, between January 1, 1991, and December 31,
      1991, were compared with similar data from official governmental agencies whose
      responsibility it is to investigate and/or document the occurrence, details, and
      characteristics of violent events resulting in death or injury. RESULTS:
      Newspapers greatly underreported suicides, rapes, and assaults, and reported
      firearms-related incidents in numbers that substantially exceeded their actual
      occurrence. CONCLUSIONS: Much information of potential value for injury
      surveillance purposes appears to be excluded from newspapers by editorial process
      and policy. Thus, newspapers are neither a valid nor reliable source for
      intentional injury surveillance purposes.

PMID- 9521363
TI  - Bishop score: a poor diagnostic test to predict failed induction versus vaginal
      delivery.
AB  - BACKGROUND: We evaluated the accuracy of the Bishop score in predicting the
      likelihood of successful labor induction (entry into active phase) in nulliparous
      and multiparous women. METHODS: During an index year, all patients having
      induction of labor and a preinduction Bishop score were included in a standard
      protocol for cervical ripening and use of oxytocin. Receiver-operating
      characteristic (ROC) curves were constructed for Bishop scores (0 to 11) to
      predict abdominal delivery for failed induction (final cervical dilation <4 cm)
      versus vaginal delivery. RESULTS: Parturients who had vaginal delivery (n = 253)
      and those in whom attempted induction failed (n = 38) did not differ
      significantly with respect to maternal demographics, length of gestation, Bishop
      score and its distribution, and infant birth weight. The area under the ROC curve
      did not differ significantly from the area under the nondiagnostic line.
      CONCLUSION: The Bishop score appears to be a poor predictor of the outcome of
      labor induction.

PMID- 9521362
TI  - Fire in the operating room during tracheostomy.
AB  - BACKGROUND: Fire in the modern operating room is still a constant danger today
      despite the usual absence of the historically explosive anesthetic gases,
      cyclopropane, and ether. During a tracheostomy, three conditions are present that
      will support an explosive or combustive event: heat, fuel and oxygen. METHODS: We
      report three routine tracheostomy cases during which a fire was ignited. One
      patient had a minor burn during the cauterizing of a bleeding vessel. There was a
      visible flame in all cases and, in one case, the cloth drapes ignited. There were
      no serious airway injuries to any patients and all had a complete and uneventful
      recovery. We duplicated the same conditions in our laboratory. RESULTS: We
      discuss each case and give effective techniques to prevent ignition during
      surgery in the future. For our study, we reproduced flames in a cadaver trachea
      using halothane and the electrocautery in an oxygen-rich environment. We describe
      a protocol that has effectively prevented tracheostomy fires in our institution
      and may decrease the risk during other procedures as well. Also, we reviewed the
      literature to provide insight into the magnitude of the problem. CONCLUSIONS:
      High-oxygen concentration, the presence of fuels such as suture and tissue, and
      an igniting spark from the electrocautery device produce the proper conditions
      for a fire during tracheostomy. Taking the proper precautions can minimize if not
      eliminate this risk.

PMID- 9521364
TI  - Epidemiology of hospitalization for near-drowning.
AB  - BACKGROUND: Although drowning is the third leading cause of accidental death
      among children less than 4 years of age, few studies have described the
      hospitalization of near-drowning victims. Our study emphasizes the local
      epidemiology and charges associated with pediatric hospitalization in cases of
      near-drowning. METHODS: Data regarding time, place, injury severity,
      circumstances, outcome, and hospital charges were collected by retrospective
      medical record review. Cross tabulation of datasets with descriptive statistical
      analysis was done using R:Base System V. RESULTS: Between 1987 and 1991, 53
      victims of near-drowning were admitted or transferred to Children's Hospital of
      Alabama in Birmingham. Thirty-three of the incidents occurred during the months
      of June, July, and August; 32 occurred in pools, 11 in lakes and rivers, 6 in
      bathtubs, 3 in mop buckets, and 1 in a cesspool. The mean hospital stay was 8
      days (combined total, 439 days), accounting for total charges of $749,507 (mean
      $14,141). Outcomes included 15 deaths, 5 discharges with neurologic sequelae, and
      33 discharges without sequelae. Private insurance covered 31 patients, 7 were
      Medicaid patients, and 15 had no coverage. CONCLUSION: Near-drowning injuries
      have high case fatality rates, a high case sequelae rate, and high
      hospitalization charges.

PMID- 9521365
TI  - Medical manners: medical students' perceptions of their own.
AB  - BACKGROUND: Because good interpersonal skills are essential for successful
      careers in primary care, we investigated senior medical students' (SMS)
      perceptions of the impression they leave with patients. METHODS: To assess the
      key elements that define the impression we make on others, we developed measures
      for self monitoring/social desirability, sensitivity, and Machiavellianism. These
      scales were used to predict SMS' attitudes toward various patient problems and
      their residency choices. RESULTS: Lower sensitivity scores and higher
      Machiavellianism scores predicted negative attitudes toward patients with
      psychologic problems. Positive attitudes toward elderly patients were predicted
      by higher self-monitoring/social desirability scores and lower Machiavellianism
      scores. Overall, women scored higher than men on self-monitoring/social
      desirability and sensitivity and lower on Machiavellianism. CONCLUSIONS: Among
      SMS, impression management's dimensions are readily measured and the students
      with the best scores tend to choose primary care careers.

PMID- 9521366
TI  - Pharmacokinetics of fentanyl during hyperthermic, isolated lung perfusion.
AB  - BACKGROUND: Hyperthermic, isolated pulmonary perfusion with tumor necrosis factor
      is a surgical procedure that isolates the pulmonary vasculature from the systemic
      circulation in patients with unresectable primary or metastatic disease confined
      to the chest. High drug levels are delivered to the perfused organ, avoiding
      systemic toxicity, and preventing loss of active drug through metabolism.
      METHODS: The pharmacokinetics of fentanyl are evaluated in three patients while
      the operative lung is hyperthermic, ventilated, and perfused with an asanguineous
      solution during nonpulsatile bypass. A loading dose of fentanyl, 1.5 microg/kg to
      2.5 microg/kg, was given during the induction of anesthesia followed by a
      continuous infusion of 150 microg/hr. RESULTS: Results showed no difference in
      mean plasma fentanyl concentrations before, during, or after bypass and was
      consistent with clearance values previously reported in healthy adult surgical
      patients in the absence of an extracorporeal circuit. CONCLUSIONS: Adjustments in
      fentanyl dosing are not required before, during, or after hyperthermic, isolated
      pulmonary perfusion is established and a steady state of fentanyl is achieved.

PMID- 9521367
TI  - Utility of dipstick urinalysis as a guide to management of adults with suspected
      infection or hematuria.
AB  - BACKGROUND: This study was done to determine whether emergency department (ED)
      patient management decisions made on the basis of dipstick urinalysis are altered
      when results of urine microscopy become available. METHODS: The study population
      was a prospective random sample of adult ED patients who had urinalysis ordered
      for detection of possible urinary tract infection (UTI) or hematuria. Clinicians
      were given the result of the dipstick urinalysis and were asked to formulate a
      management plan. Urine microscopy of the same specimen was obtained later, and
      the clinicians were asked if management was changed after results were known.
      RESULTS: Of 166 urinalyses, 118 (71%) were ordered for suspected UTI, 32 (19%)
      for suspected hematuria, and 16 (10%) for both. Of 134 urinalyses, 58 (43%) were
      positive for leukocyte esterase or nitrites, and 15 of 48 (31%) were positive for
      blood. Microscopy prompted a management change in only 9 of 166 patients. Six
      changes resulted in therapy for UTI, one resulted in withholding of therapy for
      UTI, and two resulted in cancellation of plans for diagnostic imaging. When
      urinalysis was done only to detect hematuria, none of the 32 patients had a
      management change after microscopy. CONCLUSION: Dipstick urinalysis for blood or
      UTI is a reliable diagnostic test in ED patients. In 94% of patients, subsequent
      findings on urine microscopy did not prompt a change in management. Microscopy
      added nothing to dipstick results when clinicians suspected conditions causing
      hematuria alone. Primary use of dipstick urinalysis, with microscopy in selected
      cases, would likely result in considerable cost and time saving without
      compromising patient care.

PMID- 9521368
TI  - Diagnostic problems in multiple sclerosis: overreliance on neuroimaging.
AB  - Atypical manifestations of multiple sclerosis (MS) can mislead the physician into
      misdiagnosis. The correct diagnosis of MS depends on a combination of clinical
      and laboratory evidence. The introduction of newer neuroimaging studies has
      decreased the proportion of overdiagnoses of MS. Overreliance on either clinical
      or laboratory (currently neuroimaging) data can lead to underdiagnosis. The
      physician should consider the possibility of an atypical clinical presentation of
      MS in the differential diagnosis of patients with disease of the central nervous
      system.

PMID- 9521370
TI  - Comorbidity of schizophreniform disorder and borderline personality disorder in
      an 18-year-old black woman.
AB  - We describe a rare occurrence of comorbidity of schizophreniform disorder and
      borderline personality disorder as an initial patient presentation.

PMID- 9521369
TI  - Abdominal apoplexy.
AB  - We describe the case of a patient with abdominal apoplexy, the spontaneous
      rupture of a visceral vessel. Laparotomy revealed a hematoma arising from a
      ruptured gastroepiploic artery. We report the usefulness of preoperative
      abdominal computed tomography and transgastric ultrasonography and discuss the
      condition of abdominal apoplexy. An increased awareness of the condition is
      perhaps the most valuable aspect of the early preoperative diagnosis of this
      potentially fatal condition.

PMID- 9521371
TI  - Thymoma associated with syndrome of inappropriate antidiuretic hormone secretion
      and myasthenia gravis.
AB  - We describe the association of malignant thymoma with the syndrome of
      inappropriate antidiuretic hormone secretion and myasthenia gravis. Hyponatremia
      has not been reported associated with those tumors and our case should alert
      physicians about the potential for a life-threatening complication.

PMID- 9521372
TI  - Localized fibrous nodular mesothelioma of the pelvis.
AB  - We present a case of localized fibrous nodular mesothelioma of the pelvis. There
      is one previously reported case of this uncommon pelvic tumor. We review and
      discuss the diagnostic and pathologic findings and relevant literature.

PMID- 9521373
TI  - Pulmonary embolus masquerading as pneumonia in a patient with Hodgkin's disease
      and nephrotic syndrome.
AB  - Fatal pulmonary embolus is an infrequent cause of death in patients with
      Hodgkin's disease who respond to initial therapy. This patient had associated
      minimal change disease and nephrotic syndrome that was responding to therapy, but
      had this complication. The diagnosis was delayed by the presentation that
      suggested pneumonia. A high index of suspicion for thrombotic complications and
      an aggressive diagnostic pursuit thereof are merited in these patients.

PMID- 9521374
TI  - Meningococcal cellulitis and sialadenitis.
AB  - Neisseria meningitidis is a rare cause of cellulitis. No cases of meningococcal
      sialadenitis have previously been reported. We recently successfully treated a
      patient who had meningococcal cellulitis and sialadenitis. We review previously
      reported cases of cellulitis due to N meningitidis and speculate on the role of
      underlying disease in the pathogenesis of this infection.

PMID- 9521375
TI  - Successful treatment of in-transit metastases from Merkel's cell carcinoma with
      isolated hyperthermic limb perfusion.
AB  - Merkel's cell carcinoma is an uncommon neuroendocrine cutaneous neoplasm. An
      unusual mode of dissemination of this tumor is the phenomenon of in-transit
      metastases. We report complete resolution of in-transit metastases from a
      Merkel's cell carcinoma in response to treatment with isolated hyperthermic limb
      perfusion with melphalan. Limb perfusion appears to be a promising modality for
      such lesions.

PMID- 9521376
TI  - Small cell cancer of the cervix presenting as compression of the spinal cord and
      cauda equina.
AB  - Spinal cord or cauda equina compression by metastatic cancer usually occurs
      months or even years after the diagnosis of the primary tumor. We describe the
      unusual simultaneous presentation of small cell cancer of the cervix and
      metastatic tumor compressing the spinal cord and cauda equina.

PMID- 9521377
TI  - Coexistence of primary antiphospholipid syndrome and protein S deficiency in a
      Hispanic man with ischemic stroke.
AB  - The primary antiphospholipid syndrome and protein S deficiency are known
      hypercoagulable states predisposing to ischemic strokes. The pathogenesis of
      those hypercoagulable states has been independently studied and, recently,
      interaction between them has been proposed. A 48-year-old Hispanic man had
      generalized seizures 5 months after the acute onset of a left middle cerebral
      artery infarct. He had a strong family history of strokes. After evaluation for
      cardiologic, rheumatologic, hematologic and metabolic etiologies for stroke,
      anticardiolipin antibodies and protein S deficiency were detected. Cerebral
      angiography was normal. First degree relatives were evaluated and screened for
      these conditions. Lupus anticoagulant was detected in a sister who reported a
      transient hemisensory deficit. None of the relatives studied had clinical or
      laboratory criteria for collagen vascular diseases. Coexistence of the primary
      antiphospholipid syndrome and protein S deficiency, two known prothrombotic
      states, has rarely been reported in Hispanic adults in association with ischemic
      stroke.

PMID- 9521378
TI  - Prostate cancer: to screen or not to screen?

PMID- 9521379
TI  - Impact of managed care on university-based surgical training.

PMID- 9521380
TI  - Use of corticosteroids by Australian obstetricians--a survey of clinical
      practice.
AB  - All Fellows, Members and trainees of the Royal Australian College of
      Obstetricians and Gynaecologists resident in Australia (n= 1,281) received a
      questionnaire relating to their practice of prescribing antenatal
      corticosteroids. 833 (65%) responded. The key findings were that 97% of
      Australian obstetricians prescribe antenatal corticosteroids in the classical
      setting of uncomplicated early preterm labour and 85% prescribe repeated courses
      in those cases in which the risk of preterm birth persists or recurs; 50% of
      obstetricians prescribe this agent weekly in cases with persisting risk of
      preterm birth. Some of the prescribing practices were found to be related to the
      number of years since obtaining specialist qualification. In view of the
      widespread clinical use of repeated doses of corticosteroids revealed in this
      present survey, it is clear that further research is warranted to determine the
      possible benefits and hazards of repeated exposures of the developing fetus to
      this therapy.

PMID- 9521381
TI  - The incidence of respiratory distress syndrome does not increase when preterm
      delivery occurs greater than 7 days after steroid administration.
AB  - We sought to determine if the risk of the respiratory distress syndrome (RDS) is
      increased when preterm delivery occurs greater than 7 days from the last steroid
      administration. At our hospital, steroids were repeated weekly only on
      inpatients. Linking pharmacy and delivery records, we analyzed the risk of RDS
      with preterm delivery by interval since last steroid administration. Discriminant
      function analysis revealed that adjusted for gestational age, there was a
      negative correlation between interval since last steroids administration and risk
      for RDS (p<0.05, n=254). Using analysis of variance to control more precisely for
      gestational age (28-32 weeks, n=19) we found no difference in the risk for RDS
      with longer intervals since the last steroid administration. We then used
      multiway contingency analysis to consider intervals as zero to 7 versus greater
      than 7 days and similar results were obtained. Our findings suggest that the
      process of pulmonary maturation induced by steroid administration is permanent
      rather than transient. Repetitive steroid administration does not appear to be
      beneficial. Only a large, prospective randomized trial could definitively address
      the issue of repeat steroid administration. However, on the basis of our findings
      and review of available literature, we believe there is insufficient data to
      recommend weekly repeat steroid administration to women at risk for preterm
      delivery.

PMID- 9521382
TI  - Antenatal indomethacin--adverse fetal effects confirmed.
AB  - We examined the association between antenatal indomethacin exposure and adverse
      neonatal outcome in a matched retrospective cohort study of infants born to 72
      mothers at less than 31 weeks' gestation. Indomethacin-exposed mothers were
      matched to controls by gestational age at delivery, antenatal corticosteroid
      exposure, prolonged spontaneous rupture of membranes, multiple pregnancy,
      thyrotrophin releasing hormone (TRH) exposure, and neonatal sex. Periventricular
      haemorrhage was significantly increased for infants delivered within 48 hours of
      maternal indomethacin exposure (Grade 1 and 2 19% versus 6%, and Grades 3 and 4
      28% versus 3% (p<0.03)). Persistent patent ductus arteriosus was more common in
      those infants delivered within 48 hours of maternal indomethacin exposure (40%
      versus 20% (p<0.04)). More neonates exposed to antenatal indomethacin failed to
      respond to postnatal indomethacin to close a patent ductus arteriosus, 60% versus
      0% (p<0.04). There were no adverse effects demonstrated of indomethacin
      administered greater than 48 hours from delivery. We have confirmed a probable
      association between antenatal indomethacin administration and an increased
      incidence of neonatal periventricular haemorrhage, patent ductus arteriosus, and
      impaired renal function. The adverse neonatal effects appear to be greatest when
      indomethacin is administered within 48 hours of delivery. We recommend that
      indomethacin should be used with caution as a tocolytic agent for the treatment
      of preterm labour at gestations less than 31 weeks.

PMID- 9521383
TI  - Prognosis of congenital diaphragmatic hernia.
AB  - Congenital diaphragmatic hernia (CDH) contributes significantly to perinatal
      morbidity and mortality. This retrospective study examines the experience of a
      major teaching hospital to establish survival rates and factors influencing
      outcome. Survival rates were found to relate closely to the stage at which the
      diagnosis was made and the presence of associated anomalies. Ultrasound diagnosis
      early in pregnancy is associated with a higher mortality rate than diagnosis made
      late in pregnancy or after delivery. Logistic regression analysis and chi-squared
      analysis did not establish to a significant degree that any factor, alone or in
      combination, was a reliable prognostic indicator. It is acknowledged, however,
      that figures in this series are small. Survival figures are presented to
      facilitate reliable parental counselling. In particular, the presence of
      associated major anomalies and the gestational age at which diagnosis is made are
      of critical importance in accurately counselling parents regarding the prognosis
      for survival. In this study, excluding terminations, the mortality rate for
      isolated CDH diagnosis before the 21st week was 45.5%, with a corresponding
      survival rate of 54.5%. Once the infant was liveborn, however, the survival rate
      rose to 68.0%, and if the infant survived transfer to a paediatric surgical unit,
      the survival rate in this study was 73.9 %.

PMID- 9521384
TI  - Emergency cervical suture: the obstetrician's dilemma.
AB  - We studied the perinatal mortality and morbidity associated with emergency
      cervical suture at Royal North Shore Hospital over 7 years. There were 23
      patients who had an emergency cervical suture inserted and they were divided into
      3 groups for analysis, Group 1: patients with cervical dilatation initially
      detected on routine 18-20 week ultrasonography and later confirmed on clinical
      examination, Group 2: cervical dilatation < or = 3 cm and Group 3: cervical
      dilatation >3 cm at presentation. The median delay in delivery in each group was
      6, 5 and 3 weeks respectively. The perioperative membrane rupture rate for
      emergency suture insertion in this study was 13%. The perinatal mortality rate
      for each group was 0%, 33% and 43% respectively with an overall rate of 33%.
      Follow-up at 3-5 years of 9 babies with a birth-weight < or = 1,000 g, revealed
      that of 6 survivors, 1 had moderate disability and 2 had mild disability. No
      survivors had severe disability. From the results of our study, emergency
      cervical suture can prolong gestation and in the absence of prolapsed fetal
      membranes, the perioperative membrane rupture rate is low. However, it is
      important to consider that the time gained from emergency cervical suture
      insertion may convert a previable fetus into an extremely premature infant with
      the risk of long-term disability.

PMID- 9521385
TI  - Serial transvaginal ultrasonography following McDonald cerclage and repeat suture
      insertion.
AB  - The aim of this study was to explore the hypothesis that serial transvaginal
      ultrasonography identifies early evidence of suture failure and that repeat
      cerclage delays delivery. We undertook a review of our policy of transvaginal
      ultrasonographic cervical surveillance after McDonald cerclage and of repeat
      suture insertion if persistent cervical effacement developed. Data from 26
      pregnancies in 26 women are analyzed. The women had had a total of 57 mid
      trimester miscarriages with a median of 2 (1-6) mid-trimester losses per woman.
      Twelve (46%) of the 26 women developed cervical changes at scan and underwent
      repeat cerclage. All 14 women who had a single suture inserted progressed to live
      births but 1 of the 13 women who had repeat cerclage had a mid-trimester
      miscarriage (p>0.05). The median gestation at delivery for the women who had
      repeat cerclage was 35 (22-39) weeks compared with 38 (36-40) weeks for those who
      had a single suture (p>0.05). The median interval from the detection of cervical
      changes at scan to delivery was 13 (4-19) weeks. Serial transvaginal
      ultrasonography after cervical cerclage identifies a group of women who are more
      likely to deliver preterm, and provides an opportunity for intervention (repeat
      cerclage) which appears to delay delivery by an average of 7 weeks.

PMID- 9521386
TI  - Repeat instrumental delivery: how high is the risk?
AB  - The objective of this study was to investigate whether a history of previous
      instrumental delivery imposes a higher risk of operative delivery in subsequent
      pregnancies. The outcome of labour in 108 women with 1 previous instrumental
      delivery was compared to that of 216 randomly-selected controls delivered in the
      same period. There was no difference between these 2 groups of patients in
      maternal age, height, parity, gestational age, incidence of induction of labour,
      incidence of epidural analgesia, or birth-weight of the babies. The incidence of
      instrumental delivery was found to be 8.3% among the study group, which was
      significantly higher than that of 2.3% among the control cases (relative risk =
      3.6, 95% CI 1.24 to 10.5). This increase in risk of operative delivery was
      independent to the indications for or the type of instrumental delivery in
      previous pregnancies. We conclude that women with 1 previous instrumental
      delivery are at a higher risk of repeat operative delivery. This may have
      implication in assessing patients for home delivery.

PMID- 9521387
TI  - Sublingual glyceryl trinitrate for uterine relaxation at Caeserean section--a
      prospective trial.
AB  - We report a prospective study on the use of sublingual glyceryl trinitrate at
      Caesarean section to induce uterine relaxation; 23 women were entered into the
      study with both emergency and elective cases considered. A metered dose spray was
      used to deliver a dose of 400 or 800 microgrammes of glyceryl trinitrate to the
      women. There were no major side-effects of hypotension or postpartum haemorrhage.
      The mean maximal systolic blood pressure drop in the patients following drug
      administration was 18% of the systolic pressure prior to drug administration.
      Subjective assessment of uterine tone showed the uterus to contract well
      postdelivery in response to standard oxytocic regimens. Minimal maternal side
      effects were reported. We conclude that glyceryl trinitrate is a safe form of
      uterine relaxation at Caesarean section which may be used in emergency situations
      and may also be given prophylactically in cases such as breech presentation and
      in delivery of the preterm infant where fetal trauma is possible. The use of a
      metered-dose sublingual spray is ideally suited to obstetric practice, being both
      easy to use and also rapidly administered.

PMID- 9521388
TI  - Management of the entrapped second twin: the benefits of sublingual glyceryl
      trinitrate.

PMID- 9521389
TI  - Birth centre practices in Australia.
AB  - The aim of this study was to review birth centre practices in Australia.
      Questionnaires were completed from 22 of 24 centres. Great variations were
      observed between the centres in clinical practices like number of routine
      antenatal visits, pattern of medical review, and transfer rates. Definition of
      low-risk as expressed by booking and transfer criteria also showed great
      variations, and generally these criteria became more liberal with experience.
      From 1991 to 1995 there was an average increase of approximately 1,000 bookings
      per year in the 22 centres taken together. The average transfer rate over the
      whole period was 22% antepartum and 18% intrapartum. The transfer rates increased
      slightly over the 5-year period, by 4.8% during pregnancy and 2.5% intrapartum. A
      majority was optimistic about the future, and estimated that the potential market
      for birth centres was around 16% compared with the present figure of less than
      5%. A general view was that women were not well informed about the birth-centre
      option.

PMID- 9521390
TI  - Changes in cotinine levels during pregnancy.
AB  - We measured maternal cotinine levels on residual sera of antenatal blood samples
      to biochemically document changes in smoking between early and late pregnancy. It
      was a random sample of 404 mothers who had both an early and late sample.
      Cotinine levels were used to categorize maternal smoking into nonsmoker (<15
      ng/mL) and smoker (> or = 15 ng/mL) groups. Designated smokers were further
      partitioned into lighter (15-100 ng/mL) and heavier (>100 ng/mL) semiquantitative
      groupings. There was a positive cotinine result in 113 (28%) mothers in early
      pregnancy; of these smoking women, 35 (31%) had quit smoking by the time of their
      late pregnancy blood test and 28 (25%) had reduced their cotinine level by at
      least 25%. Many more lighter smokers had quit (59%) compared to heavier smokers
      (17%) (X2 = 20.9, df=1, p<0.001). By late pregnancy, 86 (21%) mothers were still
      defined as smokers. Almost 30% of pregnant women in this sample were smoking
      during early pregnancy declining to 21% in late pregnancy.

PMID- 9521391
TI  - The incidence of gestational diabetes in multiple pregnancy.

PMID- 9521392
TI  - Comparison of perforation between single and double-gloving in perineorrhaphy
      after vaginal delivery: a randomized controlled trial.
AB  - A prospective randomized controlled trial of single and double-gloving methods in
      perineorrhaphy after vaginal delivery was performed between August 1, and
      September 30, 1996 at Rajavithi Hospital to compare glove perforation between
      both methods. We examined 1,316 individual gloves in the double-gloving method
      and 742 individual gloves in the single-gloving method. These gloves were tested
      by immersing in water. The glove perforation rate was 5.2% (107 of 2,058). There
      was significant reduction in the glove perforation rate of double-inner gloves
      (2.7%) compared with the single-gloving group (6.7%). The perforation rate of the
      double outer-gloves group was 5.9%. The perforation rate in the matched outer and
      inner perforation was found only in 0.3% (2 of 658). The double-gloving method
      had a significant benefit in protection of the surgeon's hand from the exposure
      to blood compared with the single-gloving method.

PMID- 9521393
TI  - Spontaneous abortion: short-term complications following either conservative or
      surgical management.
AB  - Spontaneous abortion is a common gynaecological condition. It is a commonly held
      belief that medical morbidity associated with this condition is low and that
      routine treatment should be surgical evacuation of the uterus. This study was
      performed to study the short-term complications of spontaneous abortion and its
      management. Transvaginal sonography (TVS) was used to determine whether retained
      products of conception (POCs) were visible inside the uterus in women presenting
      with spontaneous abortion. If tissue was present, surgical evacuation of retained
      products of conception (ERPC) was performed. If the uterus was empty, the
      patients were managed expectantly. Four hundred and seventy women were treated
      with ERPC and 297 were managed expectantly. The complication rate was 3.0% in
      those managed expectantly compared with 5.8% for those treated by ERPC. Subjects
      with no POCs on TVS can therefore be managed expectantly without increasing the
      risk of morbidity associated with this condition.

PMID- 9521395
TI  - A 6-year review of the outcome of endometrial ablation.
AB  - In June, 1995 a postal questionnaire was distributed to all 232 women who had an
      endometrial ablation at Monash Medical Centre between July, 1989 and December,
      1994. Data was analyzed from the 149 who responded. Length of follow-up ranged
      from 6 months to 6 years 6 months. Of these 78% were satisfied with their
      ablation and 84% found their menses to be lighter or to have stopped. The repeat
      ablation rate was 13% and the hysterectomy rate was 17%.

PMID- 9521394
TI  - Vaginal dinoprostone versus oral misoprostol for predilatation of the cervix in
      first trimester surgical abortion.
AB  - Prostaglandins are effective in predilatation of the cervix prior to first
      trimester surgical termination of pregnancy under local analgesia. Arandomized
      open comparative trial was devised to compare the effectiveness and acceptability
      of vaginal dinoprostone with oral misoprostol. Two groups were randomized to
      control for age, parity and ethnicity. The operation was easier and less painful
      in older, parous, and Polynesian women. Both methods were effective with respect
      to ease of dilatation. Both were acceptable and equal with respect to the level
      of pain experienced by the woman during the operation. Vaginal dinoprostone is
      more gradual in its action, but it is more expensive, has to be refrigerated and
      self-insertion may sometimes cause problems. Oral misoprostol is considerably
      cheaper and does not require refrigeration, but it was associated with more
      preoperative nausea, cramping and occasional heavy bleeding.

PMID- 9521396
TI  - Outcome of hysterectomy for pelvic pain in premenopausal women.
AB  - The outcome of abdominal hysterectomy for pelvic pain in premenopausal women was
      studied retrospectively in 228 women. In 17 women, pelvic pain was the sole
      indication while in the others, pelvic pain was one of the contributory
      indications for hysterectomy. The most common surgical histopathological
      diagnoses were uterine leiomyoma (73.9%), uterine adenomyosis (40.4%), benign
      ovarian cyst (19.3%) and endometriosis (7.9%); 118 (51.8%) patients had single
      pathology and 48.2% had multiple pathologies. The agreement between operative
      clinical diagnosis and histopathological diagnosis was 66.1% for leiomyoma, 57.1%
      for uterine adenomyosis and 30% for endometriosis. The incidence of early
      postoperative complication was 20.6%, mainly minor morbidities including urinary
      tract infection (3.9%), wound infection (3.1%) and unexplained fever (6.0%).
      These complications significantly prolonged the duration of hospital stay from an
      average of 7 days to 9-17 days. Of 98 patients with pain as the sole or the most
      predominant indication for hysterectomy, 72% responded to an outcome survey 12 or
      more months after hysterectomy. Of these, 62 (87%) were satisfied with the
      operation, 8 were unsure and 1 was dissatisfied; 68 (95.8%) patients reported
      relief of their symptoms. Relief of symptoms did not correlate with the patient's
      report of her satisfaction with hysterectomy. Pain in the abdominal wound a year
      or more after surgery was one of the commonest reasons cited for dissatisfaction
      with hysterectomy. We conclude that in well-selected cases, hysterectomy is an
      appropriate and satisfactory treatment for premenopausal women with pelvic pain
      irrespective of clinical evidence of associated pathology. Effective measures to
      reduce postoperative complications and wound pain are needed to further improve
      the outcome of abdominal hysterectomy.

PMID- 9521397
TI  - The safety of laparoscopic treatment for ovarian dermoid tumours.
AB  - Whilst laparoscopic surgery has largely replaced laparotomy as the standard
      surgical option for the management of benign ovarian cysts, concern remains
      regarding the safety of laparoscopy for benign cystic teratomas. This is based on
      a higher rate of cyst content spillage compared to laparotomy and the known
      sequelae of chemical peritonitis and granuloma formation. We present 18 cases of
      laparoscopic dermoid cystectomy with recommendations for specimen removal from
      the peritoneal cavity. Our findings together with evidence from the literature
      confirms the safety of laparoscopy for the treatment of ovarian dermoid cysts.

PMID- 9521398
TI  - Factors associated with pain following operative laparoscopy: a prospective
      observational study.
AB  - An open prospective observational study was performed, aiming to measure symptom
      severity following operative gynaecological laparoscopy and explore any
      associated factors. Women having concomitant procedures were excluded. Each woman
      had standardized analgesia, completed a symptom diary for 7 days postoperation,
      and had a standardized form completed by the surgeon detailing the operation.
      Back pain, nausea and vaginal pain were found to not be of clinical significance.
      Cutting major vessels, ligaments, vagina or ovary had major impacts on
      postoperative symptoms. In the presence of a standardized analgesic regimen,
      symptoms did not resolve for at least 5 days.

PMID- 9521399
TI  - Selection of surgery or radiotherapy as the appropriate single modality of
      treatment for Stage 1B and 2A carcinoma of the cervix.

PMID- 9521400
TI  - A phase II trial of carboplatin and etoposide for relapsed or metastatic
      carcinoma of the cervix.
AB  - This study reports the results of a phase II trial of carboplatin 100 mg/m2
      combined with etoposide 120 mg/m2 each given for 3 consecutive days every 28 days
      in women with recurrent or metastatic carcinoma of the cervix. Seventeen eligible
      patients were treated between August, 1990 and May, 1993. In the 16 evaluable
      patients, there were 2 complete responses, and no partial responses with an
      overall objective response rate of 12.5% (95% confidence interval 1.6%-38%). The
      main toxicities of this regimen related to myelosuppression and emesis. The
      combination of carboplatin and etoposide did not achieve either a better response
      rate or a substantially improved toxicity profile than is seen with single agent
      cisplatin.

PMID- 9521401
TI  - Comparison of low molecular weight heparin (Fragmin) with sodium heparin for
      prophylaxis against postoperative thrombosis in women undergoing major
      gynaecological surgery.
AB  - A randomized controlled trial was undertaken comparing the efficacy and safety of
      low molecular weight (LMW) heparin (Fragmin) with sodium heparin for prophylaxis
      against postoperative thromboembolic disease after major gynaecological surgery.
      Women were randomized to receive subcutaneous injections of 5,000 U of either
      once daily LMW heparin or twice daily sodium heparin. A total of 566 women were
      recruited, of whom 552 completed the study. Most women (461) had malignant
      disease and 430 of these underwent radical surgery. The remainder underwent
      major, but not radical surgery. There were 5 thromboembolic events in the LMW
      heparin group and 2 in the sodium heparin group, with no significant difference
      between these groups. No significant difference was found in the incidence of
      intraoperative or postoperative transfusion in the 2 groups. The decision of
      which heparin to use in routine practice cannot be made on clinical grounds.

PMID- 9521402
TI  - Implications of liver cirrhosis in pregnancy.
AB  - We present the case of a pregnant woman with alcohol-induced liver cirrhosis and
      a discussion of the clinically relevant issues of cirrhosis in pregnancy.

PMID- 9521403
TI  - Uterine rupture during preinduction cervical ripening with misoprostol in a
      patient with a previous Caesarean delivery.
AB  - We report a case of uterine rupture in a patient with a previous low transverse
      Caesarean delivery, in which transvaginal misoprostol was used for preinduction
      cervical ripening.

PMID- 9521404
TI  - A truly knotted cord.
AB  - SUMMARY: A case of 4 true knots in an umbilical cord, which did not cause any
      detectable harm, is presented. Careful examination of the placenta, membranes and
      umbilical cord continues to be encouraged.

PMID- 9521405
TI  - Antenatal true umbilical cord knot leading to fetal demise.

PMID- 9521406
TI  - Urethral diverticula in pregnancy.
AB  - In 4 cases, the clinical presentation of urethral diverticulum (UD) during
      pregnancy was a paraurethral mass (3), urinary incontinence (2), irritative
      symptoms (2), urinary tract infection (1), urethral pain and discharge (1) and
      voiding difficulty (1). The diagnosis of UD during pregnancy was made by
      transvaginal ultrasonography (2), cystoscopy (1), and after pregnancy by a
      voiding cystourethrogram (1). Management during pregnancy involved antibiotics
      (2), diverticulum aspiration (2) and incision and drainage (1). Delivery was by
      the vaginal route in 2 women with diverticular aspiration being performed during
      the second stage to aid delivery in 1 woman. Caesarean section was performed in
      the other 2 women for reasons unrelated to the presence of the UD. Three women
      had diverticulectomy performed following pregnancy for persisting symptoms.
      Although uncommon, it is important to diagnose urethral diverticula given the
      associated morbidity and the potential for causing complications during
      pregnancy.

PMID- 9521407
TI  - Endometriomas in pregnancy.
AB  - Endometriomas are rare in pregnancy, may not be large, may be difficult to
      diagnose definitively and although benign, may cause significant complications at
      any stage during gestation. They remain a management dilemma.

PMID- 9521408
TI  - Three recurrent ectopic pregnancies case report and review of the literature.
AB  - Further studies on the obstetric performance of women after recurrent ectopic
      pregnancies are needed to adequately counsel women who are still interested in
      future fertility, even after their third ectopic pregnancy.

PMID- 9521409
TI  - Ectopic pregnancy after a laparoscopically-assisted vaginal hysterectomy.

PMID- 9521410
TI  - Ectopic pregnancy in lower segment uterine scar.
AB  - A case of ectopic pregnancy in a lower uterine segment scar following previous
      Caesarean section is reported. A significant scar defect may result in deep
      implantation within the myometrium with the risk of persistent pain and bleeding
      followed inevitably by uterine rupture. In this report we discuss a number of
      management options. Except in the special situation of superficial implantation
      in a shallow scar defect where there is ultrasound evidence of continuity of the
      gestational sac with the uterine cavity we would strongly advise termination of
      the pregnancy.

PMID- 9521411
TI  - Fatal myocardial infarction associated with bromocriptine for postpartum
      lactation suppression.
AB  - Bromocriptine (Parlodel) has attracted widespread controversy for its use for
      postpartum lactation suppression because of recent reports of cerebral and
      cardiovascular complications. This case describes a maternal death in which
      bromocriptine therapy may have triggered myocardial infarction in a patient with
      asymptomatic coronary artery disease. We suggest its use with caution, especially
      in patients with identifiable risk factors of coronary artery disease or
      arteriovascular disease.

PMID- 9521412
TI  - Clear-cell carcinoma of the ovary in a 19-year-old woman.
AB  - The risk of inadvertently treating an ovarian malignancy is always present
      regardless of the patient's age, clinical history, ultrasound features, serum
      tumour markers, menopausal status and intraoperative findings. This risk can be
      minimized by paying particular attention to high-risk characteristics in any of
      the above assessment criteria and by obtaining an intraoperative frozen section
      if there is any suspicion of malignancy. The same approach should be used whether
      the initial treatment is by laparotomy or laparoscopy. We present a case of clear
      cell carcinoma of the ovary in a 19-year-old woman where there was delay in
      diagnosis and treatment as a result of an incorrect initial histopathology
      assessment. This appears to be the youngest patient reported in the literature
      with a clear-cell carcinoma of the ovary.

PMID- 9521413
TI  - High-grade borderline tumour in a transposed ovary following treatment of
      cervical carcinoma.

PMID- 9521414
TI  - Endometrial malignancy missed by office sampling.

PMID- 9521415
TI  - Extraovarian endometrioid carcinoma associated with unopposed oestrogen
      replacement therapy.

PMID- 9521416
TI  - Notable points from the recent literature.

PMID- 9521417
TI  - Re: Career paths of obstetricians and gynaecologists trained at The Royal Women's
      Hospital, Melbourne.

PMID- 9521418
TI  - Presenilin mutations in Alzheimer's disease.
AB  - The presenilins (PS-1 and PS-2) are 2 members of a novel family of genes encoding
      integral membrane proteins recently implicated in Alzheimer's disease (AD)
      pathology. To date, 43 mutations have been identified in PS-1 and 2 in PS-2 that
      lead to familial presenile AD (onset before age 65 years). The normal and
      pathological functions of the PS proteins (ps-1 and ps-2) are unknown, but their
      high degree of homology predicts similar biological activities. Homologies with
      ps from other species suggest that they may play a role in intracellular protein
      sorting and trafficking, in intercellular cell signaling, or in cell death. Since
      to date only missense mutations and in-frame deletions were identified, it is
      believed that mutated ps act through either a gain of (dys-)function or a
      dominant negative effect. In vivo and in vitro studies have linked PS mutations
      to amyloid deposition, an early pathological event in AD brains.

PMID- 9521419
TI  - Independent occurrence of somatic mutations in mitochondrial DNA of human skin
      from subjects of various ages.
AB  - The incidence (frequency of occurrence) and abundance (percentage of mutant out
      of total mtDNA population) of two different somatic mtDNA mutations in human skin
      were investigated in 44 subjects ranging from 19 to 87 years of age. Using
      quantitative allele-specific polymerase chain reaction (AS-PCR) to analyse the A-
      >G base substitution at nucleotide 3243, 50% of the samples showed detectable
      levels of that particular mutation, with abundances ranging from 0.01% to 0.12%.
      In the same set of skin samples, the overall incidence of the 4977 bp "common"
      deletion was also approximately 50%. Where detected, the abundance of this
      deletion ranged from 0.0002% to 0.1%. Comparative analyses of the incidence and
      abundance of these two mutations, collectively and in individual skin samples,
      led to these two conclusions: (1) there is independent occurrence of these two
      mtDNA mutations in human skin, and (2) whereas the 4977 bp deletion shows an age
      associated accumulation in human skin, no age association is apparent for the
      3243 A-->G base substitution. Furthermore, in general, there is a much lower
      incidence of somatic mutations in mtDNA of human skin as compared to that in
      postmitotic tissues such as skeletal muscle.

PMID- 9521420
TI  - Transcript dosage effect in familial adenomatous polyposis: model offered by two
      kindreds with exon 9 APC gene mutations.
AB  - Analysis of genotype-phenotype correlations in familial adenomatous polyposis
      (FAP) patients demonstrated that the phenotypic heterogeneity of FAP is partly
      related to the mutation site. We investigated the molecular basis for the
      difference in severity of colorectal disease observed comparing FAP patients from
      two kindreds with neighbouring germline mutations in exon 9 of the APC gene.
      Patients from one kindred presented with a attenuated form of FAP, characterized
      by a low number of colorectal adenomas (up to 22). In FAP patients from this
      kindred, the APC gene mutation was localized at codon 367, in the portion of exon
      9 that is alternately spliced. This is expected to result in the splicing-out of
      the mutation site in a fraction of mRNA molecules and in the residual production
      of wild-type transcripts from the mutant APC allele. Patients from the other
      kindred manifested a FAP phenotype characterized by hundreds of colorectal
      adenomas (320 to > 500). In these patients, the APC gene mutation abolished the
      donor site of exon 9a, used in both alternately spliced isoforms of the exon. The
      analysis of the relative levels of mutant and wild-type transcripts in unaffected
      colonic mucosa demonstrated that the mutant allele was not expressed. The model
      offered by our FAP patients with neighbouring exon 9 APC mutations supports the
      view that in addition to the mutation site, the type of mutation and transcript
      dosage effects contribute to the heterogeneity of disease phenotypes.

PMID- 9521421
TI  - Molecular heterogeneity in mucopolysaccharidosis IVA in Australia and Northern
      Ireland: nine novel mutations including T312S, a common allele that confers a
      mild phenotype.
AB  - Mucopolysaccharidosis IVA (MPS IVA) is an autosomal recessive lysosomal storage
      disorder caused by a genetic defect in N-acetylgalactosamine-6-sulfate sulfatase
      (GALNS). Previous studies of patients from a British-Irish population showed that
      the I113F mutation is the most common single mutation among MPS IVA patients and
      produces a severe clinical phenotype. We studied mutations in the GALNS gene from
      23 additional MPS IVA patients (15 from Australia, 8 from Northern Ireland), with
      various clinical phenotypes (severe, 16 cases; intermediate, 4 cases; mild, 3
      cases). We found two common mutations that together accounted for 32% of the 44
      unrelated alleles in these patients. One is the T312S mutation, a novel mutation
      found exclusively in milder patients. The other is the previously described I113F
      that produces a severe phenotype. The I113F and T312S mutations accounted for 8
      (18%) and 6 (14%) of 44 unrelated alleles, respectively. The relatively high
      residual GALNS activity seen when the T312S mutant cDNA is overexpressed in
      mutant cells provides an explanation for the mild phenotype in patients with this
      mutation. The distribution and relative frequencies of the I113F and T312S
      mutations in Australia corresponded to those observed in Northern Ireland and are
      unique to these two populations, suggesting that both mutations were probably
      introduced to Australia by Irish migrants during the 19th century. Haplotype
      analysis using 6 RFLPs provides additional data that the I113F mutation
      originated from a common ancestor. The other 9 novel mutations identified in
      these 23 patients were each limited to a single family. These data provide
      further evidence for extensive allelic heterogeneity in MPS IVA in British-Irish
      patients and provide evidence for their transmission to Australia by British
      Irish migrants.

PMID- 9521422
TI  - Glycogen Storage Disease type II: genetic and biochemical analysis of novel
      mutations in infantile patients from Turkish ancestry.
AB  - Glycogen Storage Disease type II (GSDII) is caused by the deficiency of lysosomal
      alpha-glucosidase (acid maltase). This paper reports on the characterization of
      the molecular defects in 6 infantile patients from Turkish ancestry. Five of the
      6 patients had reduced levels of the lysosomal alpha-glucosidase precursor.
      Conversion to mature enzyme was impaired in all cases, and the lysosomal alpha
      glucosidase activity in all patients fibroblasts was less than 0.5% of control.
      DNA sequence analysis revealed 3 new mutations. One mutation, found in 3 patients
      in homozygous form, was a double insertion in exon 19 (2471AG-->CAGG) leading to
      a frameshift after Pro 913. It is the first insertion mutation described in the
      lysosomal alpha-glucosidase gene. Two patients were homozygous for missense
      mutations leading to the substitution of Ser to Pro at amino acid 566 (S566P) in
      one case and of Pro to Arg at amino acid 768 (P768R) in the other. One patient
      was found to have a Gly to Arg missense mutation at amino acid 643 (G643R),
      previously identified in an adult patient (Hermans et al., 1993), combined with a
      silent second allele. The latter 3 mutations were introduced in the wild type
      lysosomal alpha-glucosidase cDNA and expressed in COS cells to analyze their
      effect. Precursor species of 110 kD were formed but the maturation was impaired.
      As a result there was an overall deficiency of catalytic activity, which is in
      accordance with the findings in the patients fibroblasts and with the clinical
      phenotype.

PMID- 9521423
TI  - Missense mutations in the chromosome 14 familial Alzheimer's disease presenilin 1
      gene.
AB  - Mutations in the presenilin genes (PS-1 and PS-2) cause early onset autosomal
      dominant Alzheimer's disease (AD). Eight early-onset, autopsy-documented familial
      AD kindreds were screened for mutations in PS-1, and seven different mutations
      were identified. Three of these were new mutations (G209V, A426P, and E120D), two
      were previously reported mutations in new families, and three mutations were
      confirmed in previously published families. Two of these new mutations are found
      within predicted transmembrane domains (TMDs 4, 7, and 8). The A426P mutation is
      the most C-terminal PS-1 mutation identified to date.

PMID- 9521424
TI  - Multiple exon screening using restriction endonuclease fingerprinting (REF):
      detection of six novel mutations in the L1 cell adhesion molecule (L1CAM) gene.
AB  - Restriction endonuclease fingerprinting (REF) has been utilized to screen 19 of
      the 28 exons in the L1CAM gene using only 5 PCR reactions. The clustered exons
      were amplified and the PCR products were subjected to endonuclease digestion and
      subsequent gel electrophoresis to produce a highly informative fingerprint for
      each PCR product. An alteration in the fingerprint, when compared to a control,
      determined the specific DNA fragment containing the mutation. Sequencing of the
      corresponding exon and flanking region was done to determine the precise location
      of the mutation. Using this method we have identified 6 novel mutations in the
      L1CAM gene in 5 patients with X-linked hydrocephalus and 2 patients with MASA.
      One of the mutations was common to both a patient with HSAS and a patient with
      MASA. The utilization of REF will allow for easier and quicker detection of
      mutations in the L1CAM gene. This method should be applicable for screening other
      genes with multiple, clustered exons.

PMID- 9521425
TI  - Evaluation of locus heterogeneity and EXT1 mutations in 34 families with
      hereditary multiple exostoses.
AB  - Hereditary multiple exostoses (EXT) is an autosomal dominant disorder
      characterized by growth of benign bone tumors. Three chromosomal loci have been
      implicated in this genetically heterogeneous disease: EXT1 at 8q24, EXT2 at
      11p13, and EXT3 on 19p. EXT1 and EXT2 were recently cloned. We evaluated 34
      families with EXT to estimate the proportion of disease attributable to EXT1,
      EXT2, and EXT3 and to investigate the spectrum of EXT1 mutations. Linkage
      analyses combined with heterogeneity testing provides strong evidence in favor of
      linkage of disease to both chromosomes 8 and 11, but does not support evidence of
      linkage to chromosome 19 in this data set. The 11 EXT1 exons were PCR-amplified
      and sequenced in all 11 isolated cases and in 20 of the 23 familial cases. Twelve
      different novel EXT1 mutations were detected, including 5 frame-shift deletions
      or insertions, 1 codon deletion, and 6 single base-pair substitutions distributed
      across 8 of the exons. Only 2 of the mutations were detected in more than one
      family. Three mutations affect sites in which alterations were previously
      reported. Nonchain-terminating missense mutations were identified in codons 280
      and 340, both coding for conserved arginine residues. These residues may be
      crucial to the function of this protein. Although the prevalence of EXT has been
      estimated to be approximately 1/50,000 individuals, the disease has been reported
      to occur much more frequently in the Chamorro natives on Guam. Our detection of
      an EXT1 mutation in one Chamorro subject will allow investigation of a possible
      founder effect in this population. Combined mutational and heterogeneity analyses
      in this set of families with multiple exostoses suggest that 66% of our total
      sample, including 45% of isolated and 77% of familial cases, are attributable to
      abnormalities in EXT1.

PMID- 9521426
TI  - Eight new mutations of the phenylalanine hydroxylase gene in Italian patients
      with hyperphenylalaninemia.
AB  - This report identifies eight new mutations of the phenylalanine hydroxylase gene
      detected in Italian patients with hyperphenylalaninemia. The trivial name of the
      mutations, predicted phenotypic effect, and population of origin (Italian region)
      are as follows: F55L (nonconservative change: classic, moderate, mild PKU ?;
      Sicily), IVS2nt-13 (splicing defect, classic PKU; Tuscany), I65N (nonconservative
      change classic, moderate, mild PKU ?; Sicily), H201Y (non-PKU HPA; Sicily), I269L
      (non-PKU HPA, or polymorphism; Sicily), IVS7nt3 (splicing defect or polymorphism;
      Sicily), I283N (classic PKU; Sicily), IVS12nt2 (splicing defect, classic PKU;
      Sicily and Apulia). In Sicily, the relative frequency of mutations F55L, I65N,
      H201Y, I269L, IVS7nt3, I283N, IVS12nt2 is < 1%. The seven new mutations
      identified in the Sicilian population increase the remarkable genetic
      heterogeneity typical of this population with an estimated homozygosity value at
      the PAH locus of 0.041.

PMID- 9521427
TI  - Novel mutations in the TIGR gene in early and late onset open angle glaucoma.
AB  - A gene for juvenile onset, open angle glaucoma (JOAG) has been localized to
      chromosome 1q21-31 in several families. Mutations in the trabecular meshwork
      induced glucocorticoid response protein (TIGR) gene, which maps to this region,
      recently have been found in families segregating both JOAG and a later onset form
      of primary open angle glaucoma (POAG). We have analysed the TIGR gene in two
      families; one Spanish family segregating autosomal dominant JOAG and an Irish
      family with a later onset form of autosomal dominant POAG. We have found a G-T
      transversion in the first base of codon 426 in all affected members of the
      Spanish family, which results in a valine to phenylalanine amino acid
      substitution. We have also found a G-A transition at the first base of codon 367
      that segregates through all but one branch of the Irish family and results in a
      glycine to arginine amino acid substitution. Members of this family that carry
      the Gly367Arg change also share a common haplotype that is neither present in any
      of the unaffected members of the family, nor in the branch that does not
      segregate the mutation. Identification of further mutations in the TIGR gene
      increases its importance in the etiology of open angle glaucoma.

PMID- 9521428
TI  - Snapback SSCP analysis: engineered conformation changes for the rapid typing of
      known mutations.
AB  - Several approaches may be applied to detect known mutations, including
      restriction enzyme cleavage, allele-specific oligonucleotide (ASO) hybridization
      or amplification, dideoxy fingerprinting, and direct DNA sequencing. All these
      approaches require several extra steps after PCR and may involve radioactive
      isotopes, time-consuming hybridization, template purification, or digestion
      steps. The ease and simplicity of the SSCP test make it a popular choice for
      mutation detection, but a significant limitation is that some DNA changes will
      not alter the overall conformation of either single strand and are thus not
      amenable to SSCP typing. We describe Snapback SSCP to genotype normal and mdx
      mice (an animal model of Duchenne muscular dystrophy) that previously could not
      be differentiated by conventional SSCP analysis. A snapback primer was designed
      with additional bases at the 5' terminus, which were complementary to the normal
      sequence flanking the mdx mutation and used under the original amplification
      conditions. Each single strand of these snapback PCR products now had one
      terminus capable of re-annealing or "snapping back" to the normal sequence but
      not the mdx mutation. In this manner, a conformation change was engineered into
      the normal strand that could be readily distinguished from the mdx allele on a
      SSCP gel. This approach could be applied to the routine screening of other known
      mutations that are not amenable to detection by simple SSCP analysis.

PMID- 9521429
TI  - Environmental organochlorine exposure and postmenopausal breast cancer risk.
AB  - Environmental exposure to organochlorine compounds has been associated with a
      potential role in breast cancer etiology, but results from previous
      investigations yielded inconsistent results. In this case-control study, we
      examined the effect of 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE),
      hexachlorobenzene (HCB), mirex, and several measures of polychlorinated biphenyls
      (PCBs) on postmenopausal breast cancer risk. The study sample included 154
      primary, incident, histologically confirmed, postmenopausal breast cancer cases
      and 192 postmenopausal community controls. Usual diet, reproductive and medical
      histories, and other lifestyle information was obtained by an extensive in person
      interview. Serum levels (ng/g) of DDE, HCB, mirex, and 73 PCB congeners were
      determined by gas chromatography with electron capture. PCB exposure was examined
      as total measured PCB levels, total number of detected PCB peaks, and three PCB
      congener groups. In the total sample, there was no evidence of an adverse effect
      of serum levels of DDE [odds ratio (OR), 1.34; 95% confidence interval (CI) 0.71
      2.55], HCB (OR, 0.81; 95% CI, 0.43-1.53), or mirex (OR, 1.37; 95% CI, 0.78-2.39).
      Further, higher serum levels of total PCBs (OR, 1.14; 95% CI, 0.61-2.15),
      moderately chlorinated PCBs (OR, 1.37; 95% CI, 0.73-2.59), more highly
      chlorinated PCBs (OR, 1.19; 95% CI, 0.60-2.36), or greater number of detected
      peaks (OR, 1.34; 95% CI, 0.72-2.47) were not associated with increased risk.
      There was some indication of a modest increase in risk for women with detectable
      levels of less chlorinated PCBs (OR, 1.66; 95% CI, 1.07-2.88). Among parous women
      who had never lactated, there was some evidence for increased risk, associated
      with having detectable levels of mirex (OR, 2.42; 95% CI, 0.98-4.32), higher
      serum concentrations of total PCBs (OR, 2.87; 95% CI, 1.01-7.29), moderately
      chlorinated PCBs (OR, 3.57; 95% CI, 1.10-8.60), and greater numbers of detected
      PCB congeners (OR, 3.31; 95% CI, 1.04-11.3). These results suggest that an
      increase in risk of postmenopausal breast cancer associated with environmental
      exposure to PCBs and mirex, if at all present, is restricted to parous women who
      had never breast-fed an infant. Future studies should consider lactation history
      of participants, as well as use similar epidemiological and laboratory
      methodologies, to ensure comparability of results across studies.

PMID- 9521430
TI  - Alcohol consumption and total estradiol in premenopausal women.
AB  - The present paper analyzes the relation between alcohol intake and serum total
      estradiol in premenopausal women while attempting to control or reduce several
      sources of variability of serum estradiol. Sixty premenopausal women were
      recruited, and alcohol intake was estimated by a semiquantitative questionnaire.
      Interviews, anthropometric measurements, and blood drawings (after overnight
      fasting) were conducted twice, 1 year apart. Both blood samples were obtained on
      the same day of the luteal phase of the cycle, in the same month and in the same
      hour and minute of the day. Samples from the first drawing were stored at -80
      degrees C. Serum from both drawings was assayed simultaneously and in blind
      fashion. A significant association between alcohol intake and estradiol was found
      when estradiol was averaged across the two visits (Spearman's r = 0.29; P <
      0.05). To control for intraindividual variability of estradiol over time,
      participants were then divided into tertiles of hormone distribution for each of
      the two sets of measurements and classified based on their consistency in
      estradiol across the two visits. Women showing consistently high estradiol levels
      at both visits were characterized by a significantly higher alcohol intake (92.8
      g/week) in comparison with those showing consistently low estradiol at both
      visits (31.6 g/week). Furthermore, the prevalence of drinkers in the group with
      consistently high estradiol was significantly higher than in the group with
      consistently low estradiol. The present report indicates that drinkers seem to be
      characterized by consistently higher estradiol than nondrinkers, and that when
      the variability of estradiol in premenopause is considered, it is possible to
      identify a relationship between alcohol intake and estradiol.

PMID- 9521431
TI  - Carcinoembryonic antigen in breast nipple aspirate fluid.
AB  - New diagnostic tools are needed to complement mammography and physical
      examinations for early detection of breast cancer, particularly among younger
      women. We evaluated the tumor biomarker, carcinoembryonic antigen (CEA), in 215
      nipple aspirate fluid (NAF) samples collected from one or both breasts of 147
      women, ages 27-87 years. Most subjects were recruited at the time of mammography
      examination. The 215 nipple fluid CEAs range from undetectable levels to 8400
      ng/ml (median, 1100 ng/ml). Normal serum CEA levels are less than 6 ng/ml. There
      are no significant differences between the CEAs in fluid from normal breasts (112
      samples) and breasts with various histories of tumors (total, 103 samples).
      Analyses for determinants of CEAs in fluids from normal breasts show higher
      levels among current smokers (P = 0.03) and marginal elevations among nulliparous
      women (P = 0.07). CEAs in these samples are not correlated with age, menopausal
      status, current hormone use, prior breastfeeding, or family history of breast
      cancer. Follow-up studies of these women and comparisons of CEAs in fluids from
      normal and cancer-containing breasts will help clarify whether this biomarker is
      useful for risk assessment or early cancer detection.

PMID- 9521433
TI  - The use of spectrophotometry to estimate melanin density in Caucasians.
AB  - The density of cutaneous melanin may be the property of the skin that protects it
      from damage by solar radiation, but there is not an accepted, noninvasive method
      of measuring it. To determine whether the density of cutaneous melanin can be
      estimated from reflectance of visible light by the skin, reflectance of 15-nm
      wavebands of light by the skin of the inner upper arm of each of 82 volunteers
      was measured at 20-nm intervals with a Minolta 508 spectrophotometer. A 3-mm skin
      biopsy was then taken from the same site, and four nonserial sections of it were
      stained with Masson Fontana for melanin. The melanin content of the basal area
      was calculated using the NIH Image analysis system. We show that cutaneous
      melanin in Caucasians can be estimated by the difference between two measurements
      of reflectance of visible light by the skin: those at wavelengths 400 and 420 nm.
      This new spectrophotometric measurement was more highly correlated (r = 0.68)
      with the histological measurements of cutaneous melanin than was skin reflectance
      of light of wavelength 680 nm (r = 0.33). Reflectances in the range of 650-700 nm
      have been used previously in skin cancer research. This relatively accurate
      measurement of melanin is quick and noninvasive and can be readily used in the
      field. It should provide improved discrimination of individual susceptibility to
      epidermal tumors in Caucasians and information about melanin's biological role in
      the causation of skin cancer.

PMID- 9521434
TI  - Factors associated with atypical nevi: a population-based study.
AB  - We conducted a case-control study to identify factors associated with the
      presence of clinically atypical nevi. Potential participants were selected, using
      a two-staged sampling scheme, from a population-based cohort of 50,000 Swedish
      women who had responded to a previous health survey questionnaire. Of 500 women
      sampled for study recruitment, 400 (80%) agreed to participate. Study
      participants underwent a physician-conducted skin examination, which identified
      130 women who had at least one clinically atypical nevus (cases) and 270 women
      without these lesions (controls). The physician-conducted skin examination also
      assessed women for benign nevus counts; other risk factor information was based
      upon responses to a health survey questionnaire. We found a strong and highly
      statistically significant relationship between number of benign nevi and the
      presence of at least one clinically atypical nevus (P < 0.0001). Women with 100
      or more benign nevi had a 26-fold increased likelihood of having an atypical
      nevus. We noted statistically significant interactions between number of benign
      nevi and other factors of interest; thus, the results are reported separately for
      women with low (<50) or high (> or =50) counts of benign nevi. Among women with
      low counts of benign nevi, the likelihood of having an atypical nevus increased
      with degree of freckling; there was also a suggested role for early sun exposure.
      Among women with high counts of benign nevi, difficulty tanning and lack of
      peeling sunburns between ages 10 and 19 appeared to increase the likelihood of
      case status; our data also suggested an inverse relationship between parity and
      atypical nevi in this subgroup.

PMID- 9521432
TI  - High levels of dipyrimidine dimers are induced in human skin by solar-simulating
      UV radiation.
AB  - UV light is considered an important contributor to skin cancer, but methods have
      been lacking to quantify specific UV-induced lesions in human skin in situ. We
      applied a newly developed 32P-postlabeling technique to measure specific UV
      induced cyclobutane dimers and 6-4 dipyrimidine lesions in the skin of healthy
      volunteers. At a dose of 400 J/m2, solar-simulated radiation caused at least 20
      cyclobutane dimers/10(6) nucleotides, which is much higher than any known DNA
      adducts induced by specific external chemical exposure in human target tissues.
      This may explain why patients with DNA repair syndromes, such as xeroderma
      pigmentosum, preferentially develop skin cancer. We applied the 32P-postlabeling
      technique to study rates of DNA repair in healthy individuals. The obtained data
      indicated a base sequence dependence of the repair process. The applied method
      has potential for the study of DNA repair as a determinant of individual
      susceptibility to skin cancer.

PMID- 9521435
TI  - Effect of supplementation with beta-carotene and vitamin A on lung nutrient
      levels.
AB  - The Carotene and Retinol Efficacy Trial (CARET), a randomized, placebo-controlled
      lung cancer chemoprevention trial of 30 mg of beta-carotene and 25,000 IU of
      retinyl palmitate, was prematurely terminated when a 46% excess lung cancer
      mortality was found in subjects on the active arm. Before the CARET intervention
      ended, 21 men were recruited to participate in a 6-month biomarker study using
      the same intervention as CARET that determined the effect of this supplementation
      on lung nutrient levels. Plasma and bronchoalveolar lavage (BAL) cell nutrient
      levels were measured before and after the intervention. The group in the active
      arm (n = 10) had plasma carotene level increases of over 10-fold, with a small
      increase in plasma retinol levels BAL cell levels of beta-carotene in the active
      group also increased 10-fold, from 4.5 to 46.3 pmol/10(6) cells (P = 0.0008),
      with no change in BAL cell retinol levels. Surgically obtained lung tissue from
      three CARET subjects in the active arm showed elevated carotene lung tissue
      levels but no increase in lung retinol levels compared to a group of surgical
      controls. Combined with our previous work showing a strong correlation between
      BAL and lung tissue nutrient levels, these findings suggest that supplementation
      with beta-carotene and vitamin A results in increased lung tissue as well as BAL
      cell levels of beta-carotene, with little change in lung retinol.

PMID- 9521436
TI  - Genetic polymorphism of CYP2D6 and lung cancer risk.
AB  - Previous reports of the association of extensive debrisoquine metabolism,
      controlled by the cytochrome P450 CYP2D6, with increased lung cancer risk have
      been conflicting. We examined the hypothesis that genetic polymorphism at the
      CYP2D6 locus identifies individuals at increased risk for lung cancer in a case
      control study of 98 incident Caucasian lung cancer patients and 110 age-, race-,
      and sex-matched controls conducted at the National Naval Medical Center,
      Bethesda, MD. Using germ line DNA, we identified inactivating mutations at the
      CYP2D6 locus (CYP2D6*3, CYP2D6*4, CYP2D6*5, and CYP2D6*6A), as well as those
      mutations that impair but do not abolish enzyme activity (CYP2D6*9 and
      CYP2D6*10A). Compared to subjects with homozygous inactivating mutations, no
      association with lung cancer was observed for those with homozygous or
      heterozygous functional alleles (odds ratios were 0.4 and 0.7, respectively).
      Furthermore, no excess risk was seen in any histological group or smoking
      category, and adjustment for smoking and sociodemographic characteristics did not
      alter the findings. Although the concept that genetic polymorphisms may
      contribute to differential lung cancer susceptibility is sound, these data do not
      support the role of CYP2D6 as a marker for elevated lung cancer risk.

PMID- 9521438
TI  - Recent use of hormone replacement therapy and the prevalence of colorectal
      adenomas.
AB  - The etiological role of hormone replacement therapy (HRT) (including estrogen
      only, combined estrogen-progesterone, and progesterone only) in colorectal
      neoplasia remains unclear. Several large studies have reported a reduced risk of
      colorectal cancer among HRT users; however, other studies have given inconsistent
      results. We examined the association between HRT and colorectal adenomatous
      polyps, precursors of colorectal cancer, among female participants in a case
      control study. Subjects were members of a prepaid health plan in Los Angeles who
      underwent sigmoidoscopy in 1991-1993. Participants received an in-person
      interview and completed a food frequency questionnaire. A total of 187
      histologically confirmed cases and 188 controls, ages 50-75 years, were included
      in the analysis. Compared with women who did not use HRT during the year before
      sigmoidoscopy, recent users had an adjusted odds ratio of 0.57 (95% confidence
      interval, 0.35-0.94). Duration of use was inversely related to the prevalence of
      colorectal adenomas, with a multivariate-adjusted odds ratio of 0.49 (95%
      confidence interval, 0.25-0.97) for use of 5 years or more. These results support
      a protective effect of HRT on colorectal adenomatous polyps.

PMID- 9521437
TI  - A prospective cohort study of intake of calcium, vitamin D, and other
      micronutrients in relation to incidence of rectal cancer among postmenopausal
      women.
AB  - To investigate whether high intakes of calcium and other micronutrients
      (carotene, retinol, and vitamins C, D, and E) are related to reduced risks of
      rectal cancer, we analyzed data from a large cohort study of postmenopausal Iowa
      women who responded to a mailed survey in 1986. After 9 years of follow-up, 144
      incident rectal cancer cases were ascertained among the 34,702 women at risk.
      Intake levels of micronutrients at baseline were derived from self-reported data
      on vitamin supplements and dietary intake of 127 foods included in a
      semiquantitative food frequency questionnaire. After adjustment for total energy
      intake and other potential confounding factors, a dose-response inverse
      association was observed between total calcium intake and the risk of rectal
      cancer: adjusted relative risks (RRs) were 1.00, 0.90, and 0.59 (trend test, P =
      0.02) from the lowest to the highest calcium intake tertiles. High intakes of
      dietary and supplement calcium were both related to a slightly reduced risk of
      rectal cancer, but neither of the trend tests was statistically significant.
      Reduced risks of rectal cancer were also observed for high intake of carotene and
      vitamins A, C, and D, although none of the associations were statistically
      significant. For vitamin D, the adjusted RRs were 1.00, 0.71, and 0.76 (trend
      test, P = 0.20) for increasing intake tertiles. Compared with women who consumed
      low levels of both total calcium and vitamin D, those in the highest intake group
      of both nutrients were at a 45% reduced risk of rectal cancer (RR, 0.55; 95%
      confidence interval, 0.32-0.93). This study supports the hypothesis that high
      intake of calcium and possibly other micronutrients may be beneficial in the
      prevention of rectal cancer.

PMID- 9521439
TI  - Analysis of histopathological features of endometrioid uterine carcinomas and
      epidemiologic risk factors.
AB  - A large case-control study was performed to determine whether risk factors for
      endometrioid carcinoma, the most common type of endometrial cancer, vary
      according to the histological features of the tumor. Study subjects consisted of
      328 women with newly diagnosed endometrioid adenocarcinoma and 320 population
      based control subjects. Variables studied included age at menarche, menopausal
      estrogen use, weight, parity, cigarette smoking, and oral contraceptive use. The
      risk factor profile for endometrioid carcinomas with and without squamous
      differentiation was very similar. No striking differences in risk factors were
      observed between endometrioid cancers with and without adjacent endometrial
      hyperplasia. Finally, none of the risk factors varied substantially between early
      stage and late-stage tumors or low-grade and high-grade tumors. In summary, this
      study indicates that risk factors for endometrioid carcinomas are not related to
      the morphological features of the tumor.

PMID- 9521440
TI  - Risk factors for high-grade cervical intraepithelial neoplasia in patients with
      mild cytological dyskaryosis: human papillomavirus testing versus multivariate
      tree analysis of demographic data.
AB  - The objective of this study was to compare the use of molecular hybridization by
      hybrid capture methodology for human papillomavirus (HPV) with the use of
      demographic and lifestyle variables as intermediate triage in patients with
      cytological mild dyskaryosis. The study was designed as a prospective study using
      regression tree analysis of demographic data in consecutive patients who were
      subjected to colposcopic evaluation at the colposcopy clinic at the First
      Department of Obstetrics and Gynaecology, University of Milan (Milan, Italy). A
      total of 177 women were subjected to colposcopy because of a single routine Pap
      smear showing mild dyskaryosis. A structured interview, sampling for HPV testing
      for the detection of viral DNA by hybrid capture methodology, and colposcopic
      evaluation with cervical biopsies were performed for each subject. The accuracies
      of molecular hybridization for HPV and of the classification model based on the
      demographic and lifestyle variables in predicting patients with histologically
      high-grade cervical intraepithelial lesions were measured. The classification
      model based on the demographic and lifestyle variables showed comparable results
      with molecular hybridization for HPV (specificity, 0.75 versus 0.73; sensitivity,
      0.61 versus 0.67, respectively). The use of demographic and lifestyle variables
      appears to be a simple and economic possibility for triaging patients with mild
      dyskaryotic smears in a screening program.

PMID- 9521441
TI  - The epidemiology of cancer of the small bowel.
AB  - Despite its anatomical location between two regions of high cancer risk, the
      small bowel rarely develops a malignant tumor. However, in recent years, small
      bowel cancer incidence rates have begun to rise. The purpose of this review is to
      explore the descriptive and analytic epidemiology of small bowel cancer for those
      factors that protect this organ and those factors associated with loss of this
      protection. Within the small intestine, the sites at the highest risk are the
      duodenum, for adenocarcinomas, and the ileum, for carcinoids and lymphomas. In
      industrialized countries, small bowel cancers are predominantly adenocarcinomas;
      in developing countries, lymphomas are much more common. The incidence of small
      bowel cancer rises with age and has generally been higher among males than among
      females. The risk factors for small bowel cancer include dietary factors similar
      to those implicated in large bowel cancer, cigarette smoking, alcohol intake, and
      other medical conditions, including Crohn's disease, familial adenomatous
      polyposis, cholecystectomy, peptic ulcer disease, and cystic fibrosis. The
      protective factors may include rapid cell turnover, a general absence of
      bacteria, an alkaline environment, and low levels of activating enzymes of
      precarcinogens. Adenocarcinomas of the small and large bowel are similar in risk
      factors and geographic distribution but not in recent time trends; colorectal
      cancer incidence rates in the United States have been falling since the mid
      1980s. Small bowel lymphoma may be associated with infectious agents, such as
      HIV. Given the differences in anatomic and geographic location among histological
      subtypes, much may be learned from well-designed, histology-specific
      epidemiological and genetic studies of cancer of the small bowel.

PMID- 9521442
TI  - The role of the serotonin transporter gene in cigarette smoking.
AB  - Data from twin studies have suggested that cigarette smoking has a significant
      heritable component. The serotonin transporter gene (5-HTT) is a plausible
      candidate gene for smoking predisposition because of its association with
      psychological traits relevant to smoking behavior. The present investigation
      evaluated the associations of smoking practices and smoking cessation with a
      common polymorphism in the upstream regulatory region of 5-HTT that is manifested
      as either an inserted (long) variant or a deleted (short) variant. The short
      variant of the polymorphism is associated with reduced transcription of the gene
      promoter and diminished uptake. A case-control study design (268 smokers and 230
      controls) was used to evaluate the associations of 5-HTT genotype with smoking
      status. Case series analysis of smokers was used to evaluate the role of 5-HTT in
      age at smoking initiation, previous quitting history, current smoking rate, and
      12-month quit rate following a minimal-contact smoking cessation program. There
      were no significant differences in the distribution of 5-HTT genotypes in smokers
      as compared with nonsmokers in either Caucasians or African Americans, nor was
      the 5-HTT genotype associated with the smoking outcome variables. However, the
      results did reveal significant racial differences in the distribution of 5-HTT
      genotypes: Caucasians were significantly more likely to carry the short variant
      of the 5-HTT gene than were African Americans (P = 0.005). These findings suggest
      that the 5-HTT gene may not play a significant role in cigarette smoking
      practices.

PMID- 9521444
TI  - Agreement of endoscopic findings and serum pepsinogen levels as an indicator of
      atrophic gastritis.
AB  - Serum pepsinogen I and II levels have recently become popular as indicators of
      atrophic gastritis in epidemiological studies. Previous studies show a
      significant association between serum pepsinogen levels and endoscopically
      diagnosed atrophic gastritis. This study assesses the level of agreement between
      the degree of atrophic gastritis as assessed by endoscopic examination and by
      serum pepsinogen assays. Study subjects were 200 outpatients at Aichi Cancer
      Center Hospital, Nagoya, Japan, who were endoscoped between February and August
      1995. Agreement of the degree of atrophic gastritis was assessed by endoscopic
      examination and by serum pepsinogen levels. Agreement in assessing the extent of
      atrophic gastritis between the two methods was 57%, and the presence of atrophic
      gastritis was 79%. Serum pepsinogen assays identify the majority of patients with
      atrophic gastritis, although they are less useful in assessing the degree of
      atrophy in detail.

PMID- 9521443
TI  - A metabolite of the tobacco-specific lung carcinogen 4-(methylnitrosamino)-1-(3
      pyridyl)-1-butanone in the urine of hospital workers exposed to environmental
      tobacco smoke.
AB  - We analyzed the urine of nonsmoking hospital workers exposed to environmental
      tobacco smoke for [4-(methylnitrosamino)-1-(3-pyridyl)but-1-yl]-beta-O-D
      glucosiduronic acid (NNAL-Gluc), a metabolite of the tobacco-specific lung
      carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. Samples were collected
      three times on a single day from nine workers. Quantitative analysis was carried
      out by combined gas chromatography-nitrosamine-selective detection. The identity
      of NNAL-Gluc was confirmed by combined gas chromatography-tandem mass
      spectrometry. The results demonstrated the presence of NNAL-Gluc in the urine of
      the exposed subjects. The mean level of NNAL-Gluc +/- SD was 0.059 +/- 0.028
      pmol/ml urine (23 pg/ml urine); range, 0.005-0.11 pmol/ml urine. Levels of NNAL
      Gluc per milliliter of urine correlated with those of cotinine (r = 0.51; P =
      0.029). These results demonstrate for the first time that NNAL-Gluc, a metabolite
      of the lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, is present
      in the urine of nonsmokers exposed to environmental tobacco smoke under field
      conditions.

PMID- 9521445
TI  - Correspondence re: R. Kim et al., Etiology of Barrett's metaplasia and esophageal
      adenocarcinoma. Cancer Epidemiol., Biomark. Prev., 6: 369-377, 1997.

PMID- 9521446
TI  - The relationship between parental yolk cholesterol and yolk fat concentration to
      abdominal fat content and feed conversion ratio of their respective offspring.
AB  - The correlation of yolk cholesterol and yolk fat concentrations of egg from the
      pedigreed Athens-Canadian Randombred control population with the percentage of
      abdominal fat (AF) and feed conversion ratio (FCR) of their progeny were studied.
      The average yolk cholesterol, yolk fat, and AF were 20.3 mg/g yolk, 244 mg/g
      yolk, and 1.64%, respectively. The phenotypic correlation of both yolk
      cholesterol and yolk fat content of eggs from the parental population with AF or
      FCR of their progeny were low and nonsignificant.

PMID- 9521447
TI  - Effects of genetic variation on total plasma protein, body weight gains, and body
      temperature responses to heat stress.
AB  - The effects of heat stress (HS) on total plasma protein (PP) concentrations, body
      weight gains (BWG), and body temperature (BT) were studied in an Athens-Canadian
      Randombred (ACRB) population and commercial broilers (BR). The populations were
      maintained at environmental temperatures of 21, 32, and 38 C from 3 to 6 wk of
      age. The PP, BWG, and mortality (M) were measured at 3, 4, 5, and 6 wk and BT at
      6 wk. After 2 wk of HS, the PP of the birds grown at 38 C was lower than that of
      birds in the 21 and 32 C environment, but differences for the 21 and 32 C groups
      were not consistent. The ACRB had significantly lower PP than the BR at 4, 5, and
      6 wk. There were no phenotypic correlations between PP and BWG within
      temperature, line, and sex. The decreased BWG of the BR in response to the HS was
      much more severe than that of the ACRB. The BT of the ACRB (41.5 C) was
      significantly lower than that of the BR (41.9 C). Birds grown at 38 and 32 C had
      a higher BT (42.0 and 41.8 C) than at 21 C (41.3 C). The BR showed an increase in
      M in both the 38 and 32 C environments, but the M for the ACRB was not affected
      by environmental temperatures.

PMID- 9521448
TI  - Genetic variation of phytate phosphorus utilization from hatch to three weeks of
      age in broiler chicken lines selected for incidence of tibial dyschondroplasia.
AB  - Ability to utilize dietary phytate P was evaluated in 1,387 broiler chicks of 45
      sire and 180 dam families, by feeding a corn-soybean base diet supplemented with
      no inorganic P and a low level of Ca. These chicks were the progeny of high and
      low incidence of tibial dyschondroplasia (TD) selected divergently for 11
      generations and a nonselected control line. Chicks from the control line utilized
      phytate P better than those from the high or low lines in terms of livability,
      mortality, and growth performance. Chicks did not differ in mortality and body
      weight between the high and low lines. Variation in livability and mortality was
      greater among lines than among families, whereas families accounted for a greater
      part of variation than lines in body weight. Dams accounted for a slightly larger
      proportion of variation than sires in traits studied. Genetic selection for
      improved utilization of dietary phytate P could be effective.

PMID- 9521449
TI  - Air velocity and high temperature effects on broiler performance.
AB  - Three trials, using a total of 1,320 male broilers, were conducted to study the
      effect of air velocity at 125 m/min on body weight gain and feed: gain. The
      broilers were placed on litter in pens in a wind tunnel or on litter in floor
      pens with conventional cross ventilation when 4 wk old. Except for air velocity,
      the conditions in the floor pens and the tunnel were the same. In Trials 1 and 2,
      only nipple waterers were used. In Trial 3, one-half of the pens on the floor and
      one-half of the pens in the tunnel were equipped with trough waterers; the
      remaining pens were equipped with nipple waterers. When compared with
      conventional ventilation, tunnel rearing improved body weight gain and feed:gain
      in all three trials. In Trial 3, waterer type did not significantly affect body
      weight gain or feed:gain in the tunnel. However, body weight gain and feed:gain
      were reduced in floor-reared birds using nipple waterers as compared with birds
      using trough waterers. The increased panting of the conventionally ventilated
      birds, as compared with the tunnel-ventilated birds, may have contributed to
      their decreased body weight gain and improved feed:gain. The lower body weights
      may occur because of the difficulty the birds experience when drinking from
      nipples while panting.

PMID- 9521450
TI  - Effect of Salmonella in young chicks on competitive exclusion treatment.
AB  - The potential of Salmonella contamination in hatching cabinets to 1) generate
      seeder chicks and 2) interfere with the efficacy of competitive exclusion (CE)
      treatments was investigated in six experiments. Hatchery-generated seeder: chicks
      were produced by hatching in the same hatcher with inoculated eggs (immersed in a
      1.0 x 10(5) cfu/mL suspension of Salmonella typhimurium or inoculated with 10(5)
      to 10(6) cells on the air cell membrane). Salmonella spread through the hatching
      cabinet to chicks hatching from uninoculated eggs in adjacent trays. In two
      experiments, Salmonella was isolated from 31 and 100% of the chick rinses after
      the birds were held in groups for 3 d in isolation units. When these hatchery
      generated seeder chicks were stocked in floor pens at a 1:10 ratio with
      uncontaminated contact chicks, the pen environment became contaminated to the
      extent that greater than 50% of the contact chicks became contaminated. In two
      experiments with only one to three inoculated eggs per 200 egg hatching cabinet,
      98% of uninoculated chicks were intestinally colonized with Salmonella after the
      birds were held 1 wk in isolation cabinets. This hatchery-acquired Salmonella
      substantially reduced the effectiveness of subsequent CE treatments to prevent
      Salmonella colonization of the young chicks. These studies demonstrate that
      control of Salmonella in hatching cabinets is critically important for control of
      Salmonella in broilers.

PMID- 9521451
TI  - Bioaccumulation and biosorption of lead by poultry litter microorganisms.
AB  - Microorganisms are known to interact with metals through a number of mechanisms,
      including binding the metals to their cells' walls and intracellular
      accumulation. Poultry litter has a high density of various microorganisms along
      with many nutrients. The objective of this research was to study the removal of
      Pb from an aqueous solution by the microorganisms found in poultry litter under
      an aerobic environment. A Pb(NO3)2 solution was treated with the aqueous extract
      of either the nonradiated litter or gamma-radiated litter in order to
      differentiate between the removal of Pb through bioaccumulation (by the living
      organisms) and biosorption (by the dead organisms). Lead removal was measured
      using anodic stripping voltammetry. Both the nonradiated and the gamma-radiated
      litter removed significant amounts of Pb. After 14 d, the amount of Pb removed
      through bioaccumulation by the nonradiated litter and through biosorption by the
      radiated litter was about 44 and 30%, respectively. There was no increase in Pb
      removal between 14 and 60 d. The biomass density of the aqueous extract of
      poultry litter increased significantly in the presence of 400 ppb Pb(NO3)2.

PMID- 9521452
TI  - Effect of yeast-supplemented feed on Salmonella and Campylobacter populations in
      broilers.
AB  - The effect of the yeast, Saccharomyces boulardii, on experimental cecal
      colonization of broilers with Salmonella typhimurium and Campylobacter jejuni was
      investigated. Duplicate pens of broiler chicks were given ad libitum access to a
      standard feed supplemented with no yeast (control), or 1 g (1x), or 100 g (100x)
      dried S. boulardii/kg feed. All chicks except negative controls were challenged
      on Day 4 with 3.2 x 10(8) cfu S. typhimurium and 6.5 x 10(8) cfu C. jejuni by
      oral gavage. After 3 wk, the broilers were euthanatized and ceca were aseptically
      removed and analyzed for Salmonella and Campylobacter. Frequency of Salmonella
      colonization was significantly (P < 0.05) reduced due to yeast treatment. Of the
      positive control birds, 70% were colonized with Salmonella; whereas only 20 and
      5% of the 1x and 100x yeast-treated birds were colonized. Mean number of
      Salmonella per gram of ceca and contents were log 1.64, 0.35, and 0.15,
      respectively, for the control, 1x, and 100x yeast-treated birds. Campylobacter
      colonization was not significantly affected by yeast treatment. Similar results
      were obtained from a second trial conducted in larger isolation floor pens.

PMID- 9521453
TI  - Effect of litter moisture and brooding temperature on body weights of turkey
      poults experiencing poult enteritis and mortality syndrome.
AB  - Studies were conducted to determine the influence of the interactions among
      litter moisture (high [HiM]> or =40% vs low [LoM]< or =20%), brooding temperature
      (high [HiB] = 38 C vs normal [NrB] = 34 C), and development of poult enteritis
      and mortality syndrome (PEMS) as indicated by body weights, relative weights of
      lymphoid organs, and mortality in Control [C] vs Infected [I] groups. There was a
      significant interaction between litter moisture and brooding temperature that had
      a significant influence on BW. The brooding temperature main effect was not
      significant, but there was a significant litter moisture effect on BW. Body
      weights were suppressed by PEMS infection, but infected poults brooded at HiB on
      LoM had significantly greater BW than those brooded at NrB and HiB on HiM. Main
      effects showed that there were significant litter moisture- and brooding
      temperature-mediated responses for BW. Relative weights of lymphoid organs
      revealed significant disease main effects but no effect due to brooding
      temperature and litter moisture. There was a significant effect of disease and
      brooding temperature with regard to mortality. The results from this study
      suggest that litter moisture influences productivity and mortality associated
      with PEMS, but brooding temperature has the greatest influence on PEMS-associated
      mortality. Therefore, higher brooding temperature for turkey poults being placed
      into a facility where they may be at risk for PEMS exposure is recommended.

PMID- 9521454
TI  - The effect of dietary supplementation with copper sulfate or tribasic copper
      chloride on broiler performance, relative copper bioavailability, and dietary
      prooxidant activity.
AB  - Three experiments were conducted to study Cu sulfate and tribasic Cu chloride
      (TBCC) as sources of supplemental Cu for poultry. In Experiment 1, 252 chicks
      were fed the basal corn-soybean meal diet (26 ppm Cu) supplemented with either 0,
      150, 300, or 450 ppm Cu from Cu sulfate or TBCC for 21 d. Chicks fed 450 ppm Cu
      from sulfate had lower (P < 0.05) feed intake than those consuming other diets.
      Feeding supplemental Cu increased (P < 0.0001) liver Cu concentration linearly
      with increasing dietary Cu regardless of Cu source. The slopes of regression of
      log10 liver Cu on dietary Cu intake did not differ between sources (P > 0.10).
      Linear regression over nonzero dietary levels of log10 transformed liver Cu
      concentration (parts per million of DM) on analyzed total Cu intake (micrograms)
      resulted in a slope ratio estimate of 106+/-19 for bioavailability of Cu from
      TBCC compared to 100 for that in Cu sulfate. In Experiment 2, a 42-d floor pen
      study was conducted with 1,260 broiler chicks given the basal corn-soybean meal
      diet supplemented with 0, 200, 400, or 600 ppm Cu from either feed-grade Cu
      sulfate or TBCC. Body weight and feed conversion did not differ in birds fed up
      to 400 ppm Cu from either source. Birds given 600 ppm Cu from either source had
      lower feed intake, poorer growth, and feed conversion (P < 0.0001). Liver Cu
      increased (P < 0.0001) linearly with increasing dietary Cu. Based on log10 liver
      Cu concentration, Cu in TBCC was 112% available compared to 100% for the standard
      Cu sulfate. In Experiment 3, Cu sources were added to broiler starter diets at
      concentrations of 25, 100, and 300 ppm Cu and diets were stored at an elevated
      temperature to examine the effect of particle size on oxidation. Diets were
      stored at 37 C for up to 20 d and samples were removed at 4-d intervals. At 300
      ppm added Cu, oxidation in TBCC diets was lower (P < 0.0001) than oxidation in
      diets fortified with coarse Cu sulfate, even though TBCC modal diameter for
      particle size was almost seven times smaller. Oxidation promotion by Cu sulfate
      was much greater with fine than in coarse sized particles for all three
      fortification levels.

PMID- 9521455
TI  - Effect of BROILACT on the physicochemical conditions and nutrient digestibility
      in the gastrointestinal tract of broilers.
AB  - The effect of the competitive exclusion (CE) product BROILACT on Salmonella
      colonization, nutrient digestibility, and the ME of the feed and the production
      of volatile fatty acids in the chicken gut was evaluated. The ileal viscosity and
      the fecal dry matter content were also determined. Newly hatched broiler chicks
      were given BROILACT orally either once on the day of hatch or five times during a
      period of 2 wk. Samples were taken at 12 and 31 d of age. In the beginning of the
      study and 2 wk later, chicks from each treatment group were taken to separate
      facilities to be challenged with Salmonella. Five and 4 d later, the chicks were
      killed and their intestines were examined for Salmonella. The results of the
      present study show that BROILACT protected the chicks against Salmonella,
      decreased the viscosity of the ileal contents, and increased the fecal dry matter
      content, and increased the ME value of the feed by 1.6% and the concentration of
      propionic acid in the cecal contents.

PMID- 9521456
TI  - Effect of hen age, body weight, and age at photostimulation. 1. Egg, incubation,
      and poult characteristics of commercial turkeys.
AB  - Turkeys from two BW groups (which averaged 11.8 and 12.9 kg, Normal and Heavy,
      respectively) were photostimulated at either 29 or 31 wk of age to determine what
      effects age-associated changes in hen carcass characteristics, egg weight, and
      egg components have on subsequent poult weight at hatching during the first 10 wk
      of production. Carcass measurements were determined from a subsample of hens 3 wk
      after photostimulation (PS). Subsamples of eggs from each PS age and BW group
      were selected for yolk and albumen measurements. All other eggs from these hens
      were individually weighed and incubated at 2-wk intervals during the first 10 wk
      of lay (4 to 14 wk after PS). All incubated eggs were reweighed at 25 d
      (transfer) and poults were individually weighed at hatch. Hen BW at PS had no
      effect on ovarian weight and follicular size or number 3 wk later. Hens
      photostimulated at 31 wk had 18.7 g heavier ovaries 3 wk after PS than hens
      photostimulated at 29 wk (P < or = 0.06), primarily due to one additional
      follicle of > or = 20 mm (P < or = 0.04). During the first 10 wk of lay, egg
      weight increased 7.8 g, 4.4 g of which was due to increased yolk weight. Eggs
      from Normal BW hens weighed significantly less than those from Heavy BW hens only
      when hens were subjected to PS at 29 wk. Egg weight at transfer relative to egg
      weight at set was significantly increased from hens 4 to 6 wk after PS compared
      with the four older production ages (6 to 8, 8 to 10, 10 to 12, and 12 to 14 wk
      after PS). There was a significant increase in poult weight with increasing hen
      production age but no changes in poult weight relative to egg weight at set. In
      conclusion, hen BW at PS had minimal effects on egg component weights and
      subsequent poult weight at hatching.

PMID- 9521457
TI  - Effect of hen age, body weight, and age at photostimulation. 2. Embryonic
      characteristics of commercial turkeys.
AB  - Turkey hens from two BW groups (which averaged 11.8 and 12.9 kg, Normal and
      Heavy, respectively) were photostimulated at either 29 or 31 wk of age to
      determine how changes in egg weight and egg component weights with hen age affect
      subsequent embryonic growth and yolk sac lipid mobilization. At 2-wk intervals
      during the first 10 wk of lay, all eggs were collected, individually weighed, and
      incubated. A subsample of eggs from each photostimulation (PS) age and BW group
      were randomly selected for yolk and albumen weight determinations and embryo
      weight, liver weight, and yolk sac measurements at 21 and 25 d of incubation.
      Yolk and yolk sac lipid measurements were done on similar sized eggs selected at
      4 to 6 and 12 to 14 wk after PS. Yolk-free embryo weight, liver weight, and yolk
      sac weight at 21 and 25 d of incubation increased during the first 10 wk of lay.
      Neither hen age nor BW at PS had any consistent effects on yolk-free embryo
      weight, liver weight, or yolk-sac weight. When similar-sized eggs (80 to 85 g)
      were selected for analyses, yolk lipid content did not change with hen production
      age. The lipid content of the yolk sac was 0.97 g greater in 21-d embryos from
      hens 12 to 14 wk after PS than from hens 4 to 6 wk after PS. Differences in yolk
      sac residual lipid and lipid subclass characteristics were not evident after 25 d
      of incubation. In conclusion, hen BW at PS or age at PS had minimal affects on
      embryonic growth during the last week of incubation, and most differences in
      embryonic growth were attributed to differences in yolk sac lipid mobilization
      between hen production ages independent of egg size.

PMID- 9521459
TI  - A broiler chick bioassay for measuring the feeding value of wheat and barley in
      complete diets.
AB  - Energy is an important component of poultry feed and is derived principally from
      cereal grains. Unfortunately, all of the chemical energy is not available to the
      bird, and biological assays must be used to determine the digestible energy value
      of a cereal grain. The bioassay described uses four pens of six male broiler
      chicks, complete diets containing 80% of a test cereal grain (with or without an
      appropriate commercial enzyme), and ad libitum feed intake. Apparent
      metabolizable energy values (kilocalories per kilogram of cereal grain, DM basis)
      values are calculated from gross energy and acid insoluble ash measurements of
      diet and excreta collected for 24 h at 16 d of age. To monitor variation between
      broiler chick assays, due to bird, environment, etc., common control samples of
      Hard Red Spring (HRS) and Canadian Prairie Spring (CPS) wheat were tested in each
      of 15 separate assays over 2 yr. Similarly, for barley, control samples of hulled
      and hulless barley were repeatedly tested in five assays. Broiler performance in
      this study was lower than expected for commercial broilers, in part due to a high
      dietary cereal grain component and the fine mash texture. However, AME values as
      determined were comparable to those reported in the literature for wheat and
      barley. The CV for AME measured among pens, representing the intra-assay CV, was
      between 1.2 and 3.4% and was lower with enzyme supplementation. The interassay CV
      was only slightly higher than the intra-assay CV. This assay provides precise
      estimations of ME in cereal grains fed to young broilers that can be used for
      diet formulation or for verification of laboratory measures of feeding value of
      cereal grains.

PMID- 9521458
TI  - Studies on the feeding of cupric sulfate pentahydrate, cupric citrate, and copper
      oxychloride to broiler chickens.
AB  - Male commercial broiler strain chickens were fed either a control diet (based on
      corn and soybean meal) or the control diet supplemented with cupric sulfate
      pentahydrate, copper oxychloride, or cupric citrate in two experiments conducted
      in floor pens. In Experiment 1, feeding copper at 125 mg/kg diet for 42 d
      significantly increased broiler growth; and the response from cupric citrate was
      significantly better than either cupric sulfate or copper oxychloride. In
      Experiment 2, the inclusion of copper from cupric citrate was reduced to 63 mg/kg
      and the length of the experiment was increased to 56 d. Cupric sulfate
      pentahydrate and copper oxychloride treatments increased weight gain by 4.9% and
      cupric citrate increased weight gain by 9.1%. The feed conversion ratios (grams
      of feed:grams of gain of live birds) in the birds fed copper were not
      significantly different from those fed the basal diet (P > 0.05) unless
      corrections were made for the weights of the dead birds; the adjusted feed
      conversion ratios (grams of feed:grams of gain of live birds + grams of gain of
      mortalities) for the copper-treated birds in Experiments 1 and 2 were 5.2 and
      7.6% lower, respectively, than the ratios of birds fed the basal diets. Plasma
      copper levels increased in supplemented chicks by 35% in Experiment 1 and 24% in
      Experiment 2. Liver copper levels in both experiments were increased by 26% with
      copper supplementation. Mortality was not affected by dietary treatment in either
      experiment (P > 0.05).

PMID- 9521460
TI  - Comparison of sample source (excreta or ileal digesta) and age of broiler chick
      on measurement of apparent digestible energy of wheat and barley.
AB  - The broiler chick bioassay measures AME of wheat- or barley-based diets, with or
      without an enzyme, from excreta (24-h collections at 8 or 16 d) and ileal digesta
      (17 d). The objective was to discuss the merits and accuracy of sample source
      (excreta vs ileal digesta) and bird age for determining the feeding value of
      wheat and barley. The bioassay utilized 80% of a test cereal grain, 20% basal
      diet containing 1.1% acid insoluble ash marker, and fed with or without an enzyme
      to four pens of six male broilers from 4 to 17 d. A total of 138 wheat and 97
      barley samples (with and without an enzyme) were tested in 15 and five bioassays,
      respectively. Within each wheat or barley bioassay two control wheat and barley
      samples were measured. The among-pens and between-assays CV for AME were
      calculated for these control samples, and correlation coefficients between the
      measures were calculated for the controls and for all of the 138 wheat and 97
      barley samples included in the assays. For wheat samples, values for AME were
      lowest for excreta samples collected at 8 d, and similar for excreta and ileal
      digesta samples collected at 16 and 17 d, respectively. For barley samples, the
      three values were significantly different. The among-pens and between-assay CV
      were low for AME among both wheat and barley samples. Correlation coefficients
      between several measures of AME at 8 and 16 d were significant for the control
      samples with enzyme supplementation. When all samples were included in the
      analysis, correlation coefficients between AME measures were moderate to high. On
      the basis of accuracy, precision, and cost, these data favor measuring AME on
      excreta samples at 16 d of age. Comparisons of number of pens of broilers used to
      determine AME would suggest that much of the variability predicted with four pens
      of six broilers each could be achieved with three, and possibly two pens of six
      broilers each, thereby greatly increasing the capacity of the assay to screen
      large numbers of samples.

PMID- 9521461
TI  - Transforming growth factor-beta gene expression in avian Low Score Normal
      pectoral muscle.
AB  - The avian Low Score Normal (LSN) genetic muscle weakness is phenotypically
      characterized by a reduction in the ability of birds to right themselves from a
      supine position. In previous studies, LSN birds exhibited elevated levels of
      decorin transcript and protein at embryonic Day 20 and a large increase in
      collagen crosslinking at 6 wk posthatch. Transforming growth factor-beta (TGF
      beta) expression has been reported to control decorin expression. Steady state
      levels of TGF-beta1 and TGF-beta2 transcripts were determined in ovo and
      posthatch in order to initiate an investigation of the mechanism underlying
      decorin expression. On embryonic Day 20 through 1 wk posthatch, TGF-beta2
      transcript levels were elevated, whereas an increase in TGF-beta1 was only noted
      at 1 d posthatch. These data suggest that the increase in decorin expression may
      be associated with a modification in a TGF-beta signal transduction pathway.

PMID- 9521462
TI  - Using response surface analysis to optimize the quality of ultrapasteurized
      liquid whole egg.
AB  - Response surface analysis (RSA) is used to show the effects of a range of heat
      pasteurization times and temperature combinations on several quality factors of
      liquid egg. The purpose of this paper is not to suggest the rigid processing time
      and temperature combinations to give maximum quality but to illustrate that RSA
      can be used as a tool to predict individual and multiple egg functional
      properties resulting from various processing conditions. The application of heat
      will change the quality and functional properties of the liquid egg. This paper
      describes the application of RSA to the changes in soluble protein, alpha
      amylase, solids content, viscosity, and the height of cakes made with processed
      liquid whole egg (LWE). The Mallow's Cp statistic is used to determine the best
      model while minimizing the number of terms in the model. By using this method of
      choosing the model, the number of terms desired in the model can be first
      determined then the best fit can be determined from the possible models. The time
      and temperature combinations are in the ultra-high temperature range for eggs
      (30, 60, and 95 s each at 64, 68, and 72 C). The RSA may be used to optimize the
      quality and functionality of LWE while ensuring the safety of the product. This
      information can be used (with further testing) to maximize desirable and minimize
      undesirable product properties.

PMID- 9521464
TI  - Sensory and instrument-measured ground chicken meat color.
AB  - Instrument values were compared to sensory perception of ground breast and thigh
      meat color. Different patty thicknesses (0.5, 1.5, and 2.0) and background colors
      (white, pink, green, and gray), previously found to cause differences in
      instrument-measured color, were used. Sensory descriptive analysis scores for
      lightness, hue, and chroma were compared to instrument-measured L* values, hue,
      and chroma. Sensory ordinal rank scores for lightness, redness, and yellowness
      were compared to instrument-generated L*, a*, and b* values. Sensory descriptive
      analysis scores and instrument values agreed in two of six comparisons using
      breast and thigh patties. They agreed when thigh hue and chroma were measured.
      Sensory ordinal rank scores were different from instrument color values in the
      ability to detect color changes caused by white, pink, green, and gray background
      colors. Instrument values agreed with sensory scores for lightness only when
      white and pink backgrounds were used. Instrument and sensory methods agreed when
      a* values and redness scores were compared using each of the backgrounds. The
      sensory panel did not detect differences in yellowness found by the instrument
      when samples on white and pink backgrounds were compared to samples on green and
      gray backgrounds. A majority of panelists (84 of 85) preferred samples on white
      or pink backgrounds. Red color of breast patties was associated with freshness.
      Reflective lighting was compared to transmission lighting using patties of
      different thicknesses. Sensory evaluation detected no differences in lightness
      due to breast patty thickness when reflective lighting was used. Increased
      thickness caused the patties to appear darker when transmission lighting was
      used. Decreased transmission lighting penetrating the sample made the patties
      appear more red. Reflective lighting made thigh patties appear lighter. Lightness
      decreased when thigh patty thickness increased with both reflective and
      transmission lighting. Transmission lighting made the thigh patties appear more
      yellow as patty thickness increased.

PMID- 9521463
TI  - Fluorometric analysis of 2-thiobarbituric acid reactive substances in turkey.
AB  - Three experiments were conducted to develop a sensitive and reliable fluorometric
      thiobarbituric acid (TBA) reactive substances (TBARS) method to determine lipid
      oxidation products in meat. The first study was conducted to find the optimum
      sample preparation conditions for meat in the fluorometric method. The second
      study was to compare the original and the modified methods by using meat and
      blood samples. The modified fluorometric method was compared with a conventional
      spectrophotometric method in a third study. Four different extraction solutions
      (2.5 M acetic acid, 0.5 M hydrochloric acid, 0.8 M perchloric acid, and 1.4 M
      trichloroacetic acid) and two ratios of extraction solution to TBA (20 mM)
      solutions (2:1 and 1:1) were examined in the first study. Hydrochloric acid was
      the optimum among the four extraction solutions tested, and the ratio of
      extraction solution to TBA solution at 1:1 was the best for the fluorometric
      TBARS method in raw ground turkey. The modified fluorometric method had high
      recovery rates (91%, average), and the regression coefficient of the standard
      curve prepared with spikes was also high (r2 = 0.99). The analysis of raw meat
      and plasma samples indicated that the modified fluorometric method had greater
      sensitivity than the original method. The pH of the reaction mixture played an
      important role in extraction TBARS from samples, and low pH conditions were
      preferable to high pH conditions. The amount of lipid oxidation products in raw
      turkey breast meat indicated that the fluorometric method had much greater
      sensitivity than the spectrophotometric method. The results from the three
      studies showed that the modified fluorometric TBARS method was useful for the
      samples with low lipid oxidation products, such as fresh raw meat. The
      sensitivity of the modified fluorometric method also facilitates the
      determination of oxidation products in small quantities of samples.

PMID- 9521465
TI  - Influence of preslaughter stunning on turkey breast muscle quality.
AB  - Pectoralis muscle quality was evaluated from 18-wk-old tom turkeys after
      electrical stun, carbon dioxide stun, or no stun methods were applied. Color was
      measured on raw muscle and cooked meat using a colorimeter. Muscle pH was
      measured 15 min post-mortem (initial), 24 h post-mortem (final), and after
      cooking. The right Pectoralis muscle of each carcass was excised for m-calpain
      analysis within 4 min post-mortem. After 24 h of storage at 4 C, the left
      Pectoralis muscle was excised to determine cook loss and shear force
      measurements. No significant difference was found in initial muscle pH (15 min)
      from turkeys receiving electrical or carbon dioxide stunning, 6.36+/-0.15 and
      6.20+/-0.14, respectively. However, initial muscle pH for birds that were not
      stunned (5.99+/-0.08) was lower (P < 0.05) than the muscle pH of birds stunned
      using either of the two stunning methods. Stunning method had no effect on the
      final muscle pH, raw muscle color, cooked meat pH, cooked meat color, cook loss,
      or shear force. Cook loss was found to positively correlate with initial muscle
      lightness (r = 0.53), and cooked meat lightness (r = 0.48), but to negatively
      correlate with cooked meat yellowness (r = -0.48) and shear strength (r = -0.43).
      m-Calpain activity declined with the stunning methods in the following order:
      electrical > carbon dioxide > no stun. In addition, m-calpain activity was found
      to correlate with initial muscle pH (r = 0.95) and with cooked meat shear force
      (r = -0.43). The results of this study show that electrical stunning, carbon
      dioxide stunning, and no stunning methods provide comparable cooked turkey breast
      meat quality with no consistent differences after aging on the carcass for 24 h.

PMID- 9521466
TI  - Dietary marine algae maintains egg consumer acceptability while enhancing yolk
      color.
AB  - A drum-dried docosahexaenoic acid (DHA; C22:6n-3) enriched marine microalgal
      product (MA) was investigated as a n-3 fatty acid (n-3 FA) source in laying hen
      diets. Hen diets were supplemented with 2.4 or 4.8% MA. Eggs were analyzed for
      yolk color following 4 wk of feeding as well as weekly for 4 wk. Egg flavor was
      evaluated by consumer panelists. Feeding MA significantly (P < 0.01) increased
      yolk a* values in a dose response manner as early as 1 wk post-MA feeding.
      Consumer panelists found n-3 FA enriched eggs as acceptable as typical eggs.
      These data suggest that dietary MA is useful for enhancing yolk n-3 FA and color
      while maintaining consumer acceptability of the resulting egg product.

PMID- 9521467
TI  - DNA copy number changes in alveolar soft part sarcoma: a comparative genomic
      hybridization study.
AB  - Alveolar soft part sarcoma (ASPS) is a rare, histologically distinctive soft
      tissue sarcoma typically occurring in children and young adults. Although the
      tumor often shows focal expression of muscle markers, its relationship with
      rhabdomyosarcoma is not established. The genetic background of ASPS is poorly
      understood. This study was undertaken to analyze the DNA copy number changes in
      13 cases of ASPS using comparative genomic hybridization (CGH) on formaldehyde
      fixed, paraffin-embedded tissue sections. Four ASPS cases showed DNA copy number
      changes. Gains were more common than losses. Gains observed in more than one case
      included 1q, 8q, 12q and 16p. Although these findings do not show consistent DNA
      copy number changes in ASPS, they give preliminary clues to genomic areas that
      might be important in the pathogenesis of ASPS.

PMID- 9521468
TI  - Localization of prohormone convertases 1/3 and 2 in the human pituitary gland and
      pituitary adenomas: analysis by immunohistochemistry, immunoelectron microscopy,
      and laser scanning microscopy.
AB  - Prohormone convertase (PC) 1/3 and PC2 are involved in post-translational
      processing of endocrine tissues, including the pancreatic islets and pituitary
      glands. Our immunohistochemical studies disclosed the presence of PC1/3 and PC2
      in non-neoplastic pituitary glands, especially in corticotrophs, gonadotrophs,
      and thyrotrophs. Among 58 pituitary adenomas obtained by trans-sphenoidal
      surgery, adrenocorticotropin (ACTH)-secreting adenomas showed a high incidence of
      the presence of PC1/3 and PC2, i.e., nine of nine cases were positive for ACTH.
      Five of nine cases showed consistency between PC2 localization and alpha
      melanocyte stimulating hormone immunoreactivity, which suggests the functional
      correlation between PC2 and the processing of ACTH. In four cases, we observed
      inconsistency in immunolocalization, which suggested the possibility of inactive
      PC2 and abnormal processing of alpha-melanocyte stimulating hormone. The high
      incidence of PC1/3 and PC2 in nonfunctioning adenomas might be related to the
      processing of chromogranin A.

PMID- 9521469
TI  - Microvillous lymphomas are B-cell neoplasms that frequently express CD56.
AB  - Microvillous lymphomas (MVLs) are rare, poorly defined, large transformed cell
      lymphomas characterized by a cohesive sinus growth pattern and ultrastructural
      cytoplasmic processes. Most MVLs express B-cell antigens and have been compared
      ultrastructurally to transformed follicular center cells and follicular dendritic
      cells. For additional definition of the immunophenotype of these unusual B-cell
      lymphomas, we evaluated eight cases of MVL for B-cell-associated antigens (CD21,
      CD35, CDw75, DBA.44, bcl-2) using paraffin immunoperoxidase. CD56, the neural
      cell adhesion molecule, was tested because of the unusual, cohesive, sinus
      pattern of tumor cell growth seen in MVL. Molecular analysis for immunoglobulin
      heavy chain and bcl-2 gene rearrangements was performed to confirm B-cell
      clonality and to evaluate cases for possible follicular origin. All of the cases
      were marked as B cells (CD20 positive), and the clonal nature confirmed by
      immunoperoxidase in five cases (63%) of eight and polymerase chain reaction for
      immunoglobulin heavy chain in seven cases (88%) of eight. CDw75 staining was
      present in six cases and CD74 in seven. DBA.44 and CD21 and CD35 were negative in
      all of the cases, and four cases (50%) of eight expressed CD56. bcl-2 protein
      expression was seen in seven of eight cases; bcl-2 gene rearrangement was present
      in one case (33%) of three studied. In conclusion, MVLs are B-cell lymphomas
      demonstrating clonal immunoglobulin heavy chain gene rearrangement. The
      neoplastic cells express CDw75 and bcl-2 protein. The presence of bcl-2
      rearrangements in a limited number of cases implies that at least some MVLs have
      a follicular origin. Fifty percent of MVLs express CD56, suggesting a role for
      adhesion molecules in the distribution of this lymphoma.

PMID- 9521470
TI  - Immunohistochemical expression of retinoblastoma and p53 tumor suppressor genes
      in prostatic intraepithelial neoplasia: comparison with prostatic adenocarcinoma
      and benign prostate.
AB  - Mutational alterations involving the p53 and retinoblastoma (RB) tumor suppressor
      genes are implicated in the oncogenesis of a variety of tumors. Their role in the
      pathogenesis of prostatic adenocarcinoma remains to be fully elucidated, and
      their detection in high-grade prostatic intraepithelial neoplasia (HG-PIN) has
      not been closely examined. We studied the immunohistochemical expression of RB
      and p53 proteins in HG-PIN, benign prostate, and prostatic adenocarcinoma from 25
      radical prostatectomy specimens. Formalin-fixed, paraffin-embedded tissue
      sections pretreated with antigen retrieval in citrate buffer were stained with
      anti-RB antibody RB-WL-1 and anti-p53 antibody DO-7. RB immunoreactivity was
      present in all of the cases in the foci of HG-PIN, benign prostate, and prostatic
      adenocarcinoma. Mutant p53 protein was detected in 56% of HG-PIN, 72% of
      prostatic adenocarcinomas, and 20% of benign prostatic glands. A multivariate
      analysis of variance showed an overall difference in p53 immunoreactivity between
      HG-PIN, benign prostate, and prostatic adenocarcinoma (P < .001). There was a
      statistically significant difference between immunoreactivity of the benign
      prostate and of HG-PIN (P < .001) and between the immunoreactivity of benign
      prostate and prostatic adenocarcinoma (P < .001). The immunoreactivities of HG
      PIN and prostatic adenocarcinoma were not statistically different (P = .3). These
      data suggest that RB loss might not play a role in initiation of all cases of
      prostatic adenocarcinoma. The p53 immunoreactivity in HG-PIN was significantly
      different from that found in benign prostate and was similar to that of prostatic
      adenocarcinoma. This is in keeping with the putative premalignant character of HG
      PIN.

PMID- 9521471
TI  - Primary pulmonary glomus tumor: a clinicopathologic and immunohistochemical study
      of two cases.
AB  - We present two cases of glomus tumors arising within the lung parenchyma. The
      patients are a 40-year-old man and a 51-year-old man. Clinically, the two men
      were asymptomatic, and the pulmonary tumor was detected during a routine chest
      roentgenographic examination. Complete surgical resection of the pulmonary tumors
      was performed. Grossly, the tumors measured 1.1 and 1.5 cm. in greatest
      dimension; they were well circumscribed and subpleural. Neither tumor showed
      evidence of invasion of lung or pleura. Histologically, both tumors had
      pseudocapsules, lacked invasion of surrounding lung structures, and demonstrated
      the appearance of the solid/mucohyaline, or "glomus tumor proper" type of
      neoplasm. This included oval-to-round cells, with central uniform nuclei;
      variably eosinophilic-to-clear cytoplasm; and well-demarcated cell borders in
      close proximity to a rich vascular supply showing perivascular fibrosis.
      Immunohistochemically, both tumors showed diffuse, moderate-to-strong staining
      for vimentin, muscle-specific actin, and smooth muscle actin. One tumor also
      showed diffuse strong staining for desmin, whereas the other was negative. Follow
      up information obtained from one of the patients revealed that he was alive and
      well 47 months after surgical resection. Our cases highlight the ubiquitous
      distribution of glomus tumor and its similar histologic appearance and
      immunohistochemical profile to soft tissue glomus tumors.

PMID- 9521472
TI  - Do prognostic marker studies on core needle biopsy specimens of breast carcinoma
      accurately reflect the marker status of the tumor?
AB  - Core needle biopsies (CNB) are often used for the diagnosis of breast lesions. In
      some breast cancer patients, e.g., those treated with preoperative chemotherapy,
      the CNB specimen might be the only pretreatment tissue sample available for
      studies of prognostic and predictive markers. Our purpose was to evaluate whether
      marker studies performed on CNB specimens accurately reflect the marker status of
      the tumor. Immunostaining for five commonly used prognostic and predictive
      markers was performed on both CNB and subsequent excision specimens from 56
      consecutive patients who had a CNB with carcinoma followed by excision of the
      tumor. None of the patients received radiotherapy or chemotherapy between the CNB
      and the excision. Paraffin sections of the CNB and excision specimens were
      immunostained for bcl-2, estrogen receptor (ER), c-erbB-2, and p53. These markers
      were scored as positive or negative. Microvessel density (MVD) was scored as a
      continuous variable on sections immunostained for Factor VIII-related antigen by
      calculating the average number of microvessels in three 224x fields of highest
      tumor vascularity ("hot spots"). Immunostaining results for bcl-2, ER, c-erbB-2,
      and p53 on the CNB and the corresponding excision specimens were 100% concordant.
      Although there was significant correlation between MVD on the CNB specimens and
      the corresponding excisions (r = 0.507, P = 0.0002), the mean MVD on the CNB and
      corresponding excision specimens differed by more than 10% in 85.7% of cases,
      with differences ranging from 4.3 to 233.3%. MVD was higher in the CNB than in
      the excision specimens in 30 (61.2%) of 49 cases. In conclusion, in all of the
      cases studied, accurate results for the dichotomously scored markers bcl-2, ER, c
      erbB-2, and p53 were obtained on CNB specimens. In contrast, in most cases, MVD,
      which was scored as a continuous variable, could not be reliably assessed on the
      CNB specimen.

PMID- 9521473
TI  - Coexpression of parathyroid hormone-related protein and its receptor in breast
      carcinoma: a potential autocrine effector system.
AB  - Parathyroid hormone-related protein (PTHrP), the pathogenic factor in most cases
      of humoral hypercalcemia of malignancy, is also expressed by many normal tissues.
      Its diverse biologic activities in these tissues are mediated by the PTH/PTHrP
      receptor through autocrine and paracrine mechanisms. Recent data suggest that
      PTHrP and its receptor might also influence the growth and metastatic spread of
      some cancers through similar local actions. Accordingly, immunohistochemical
      studies using murine monoclonal antibodies to detect coexpression of PTHrP and
      the PTH/PTHrP receptor were performed on 52 invasive breast carcinomas to assess
      the existence of this potential autocrine effector system. All of the 52 invasive
      breast carcinomas expressed reactivity for PTHrP, and 50 (96%) of these tumors
      also expressed reactivity for the receptor. Although additional investigations
      are necessary for evaluation of the role of PTHrP and PTH/PTHrP receptor in tumor
      pathogenesis, our current study demonstrates the presence of this potential
      autocrine effector system in the great majority of invasive breast carcinomas.

PMID- 9521474
TI  - Expression of rasGTPase activating protein in basal cell carcinoma of the skin.
AB  - The ras proto-oncogene, a key component in the signal transduction cascade of
      activated growth factors, is involved in multiple tumor types, including basal
      cell carcinoma (BCC). rasGTPase activating protein (rasGAP), is a dual function
      protein in the ras signaling pathway, i.e., it downregulates activated ras via
      its catalytic domain, and it also participates in the downstream effector
      signaling pathway by mediating protein-protein interaction. Missense mutations
      presumably leading to rasGAP activation were previously detected in this gene, in
      a subset of BCCs. To assess the role of rasP21 and rasGAP in BCC tumorigenesis,
      we performed an immunohistochemical analysis of 48 BCCs, of which 45 were of the
      circumscribed variant (indolent-growth tumors) and the remaining 3 (2
      morpheaform, 1 infiltrative), were aggressive-growth variants. rasGAP
      overexpression was demonstrated in 7 of 48 BCC cases, i.e., in 4 (8.8%) of 45
      indolent-growth cases and in all of the 3 aggressive-growth cases. We detected
      tumor-specific reduction of rasP21 levels in 5 (11.1%) of 45 cases. There was no
      overlap between the tumors displaying rasGAP and rasP21 alternations and a high
      proliferation index, as assessed by Ki-67 staining, except for one case of
      aggressive-growth variant. We conclude that rasGAP overexpression is associated
      with BCC tumorigenesis in a ras-independent manner, is not reflective of the
      proliferation status of the tumor, and is more characteristic of aggressive
      growth BCCs.

PMID- 9521476
TI  - Scrotal leiomyomas with bizarre nuclei: a report of three cases.
AB  - We discuss here three cases of scrotal leiomyoma with bizarre nuclei. The
      patients, ranging in age from 44 to 58 years, presented with painless scrotal
      masses that were clinically diagnosed as cysts. Clinical follow-up, available for
      two of the patients, revealed no evidence of local recurrence or distant
      metastasis 5 years after resection. The tumors were well circumscribed and ranged
      from 2 to 3 cm in maximal diameter. They were characterized by interlacing
      fascicles of spindle-shaped cells with pleomorphic nuclei. Nuclei were large and
      multilobulated with hyperchromatic chromatin and macronucleoli. Multinucleated
      tumor cells were infrequent. Intranuclear invagination of eosinophilic globules
      of cytoplasm produced pseudonucleoli. There was no mitotic activity.
      Immunohistochemically, the tumor cells expressed vimentin, desmin, smooth muscle
      actin, and muscle-specific actin, but not cytokeratin, neurofilament, or glial
      fibrillary acidic protein. In contrast to scrotal leiomyosarcomas, scrotal
      leiomyomas with bizarre nuclei are not hypercellular, and they lack mitotic
      activity.

PMID- 9521475
TI  - Heterogeneous expression of E-cadherin and p53 in prostate cancer: clinical
      implications. BIOMED-II Markers for Prostate Cancer Study Group.
AB  - Histologic grade and tumor volume are markers of malignant phenotype. More
      objective markers, however, have been sought for needle biopsy specimens. The aim
      of this study was to evaluate how immunohistochemical expression of the potential
      prognostic markers E-cadherin and p53 in biopsy specimens relates to the
      expression of these markers in prostatectomy specimens. Therefore, we analyzed 47
      prostatectomy specimens and their preoperative biopsy specimens. Fixation of
      surgical specimens and the immunohistochemical assay for both E-cadherin and p53
      expression was optimized. All paraffin blocks containing areas of carcinoma were
      submitted for immunohistochemical analysis. The prevalence of abnormal p53
      immunoreactivity was only 11%. In addition, abnormal p53 expression was virtually
      restricted to cases that were already identified as having a poor prognosis on
      the basis of the large volume and the high grade of their carcinomas. In 28% of
      the cases, we found abnormal immunoreactivity for E-cadherin. These cases
      revealed considerable heterogeneity in topographic distribution of abnormal
      expression. The level of sensitivity to the detection of abnormal E-cadherin
      expression or abnormal p53 in the prostatectomy specimen was 15% and 60%,
      respectively. In view of the inherent heterogeneity of E-cadherin expression and
      the low prevalence of abnormal p53 expression, we question the use of these
      markers for prognostic purposes in needle biopsy specimens. Unless representative
      sampling by needle biopsy can be assured, the use of E-cadherin expression will
      be of most value in prostatectomy specimens.

PMID- 9521477
TI  - Histologic assessment of Helicobacter pylori status after therapy: comparison of
      Giemsa, Diff-Quik, and Genta stains.
AB  - To compare the Giemsa, Diff-Quik, and Genta stains for detection of Helicobacter
      pylori in gastric biopsy specimens, we stained, coded, and randomized slides,
      which were then independently reviewed by two pathologists and one trainee. H.
      pylori was graded from 0 (absent) to 5 (maximal intensity). Negative cases were
      from recently cured patients to ensure that a background of chronic inflammation
      was present. The time required to complete the evaluation was tabulated. The
      pathologists interpreted 72 H. pylori-negative slides, of which 1 (1.3%), 2 (3%),
      and 3 (4%) were scored positive (each with the score of 1) with Diff-Quik, Genta,
      and Giemsa stains, respectively (P = ns). Of the 128 H. pylori-positive slides, 5
      (4%) had false-negative results with Diff-Quik, 8 with Genta (6%), and 14 with
      Giemsa stains( 11%). No Grade 2 slides were missed by Genta or Diff-Quik stains,
      but 3 of 20 were missed by Giemsa stain. The combination of hematoxylin and eosin
      and Diff-Quik provides accuracy similar to that of the Genta stain but requires
      more processing time. No stain was excellent after therapy for detecting one or
      two bacteria per slide; this finding emphasizes the need for obtaining multiple
      biopsy specimen to exclude failure of H. pylori therapy.

PMID- 9521478
TI  - Submucosa 1.0 x 0.1 mm in size is sufficient to count inflammatory cell numbers
      in human airway biopsy specimens.
AB  - Counting of inflammatory cells in human airway biopsy specimens is difficult
      because immunopositive cells are present in varying density in lung tissue. The
      goal of our study was to assess the minimal amount of tissue that is necessary
      for the counting of constant cell numbers. In bronchial biopsy specimens from 5
      healthy controls and 5 patients with asthma, we evaluated 20 successive areas of
      submucosa 0.1 x 0.1 mm in size. We recorded positive and negative changes of more
      than 10% in the counted numbers of CD4-, CD8-, and EG2-positive cells. We
      demonstrated that tissue 1.0 x 0.1 mm in size, along 1-mm basement membrane, is
      sufficient to obtain constant cell numbers.

PMID- 9521479
TI  - The common 4977 base pair deletion of mitochondrial DNA preferentially
      accumulates in the cardiac conduction system of patients with Kearns-Sayre
      syndrome.
AB  - Previous studies of cytochrome c oxidase (complex IV of the respiratory chain) in
      the heart of a 26-year-old man with longstanding Kearns-Sayre syndrome and fatal
      congestive cardiomyopathy had revealed the presence of randomly distributed
      enzyme-deficient cardiomyocytes, both in the contractile and the conducting
      myocardium. In the present study, the conduction system of the heart was screened
      for the occurrence of the common 4977 base pair deletion (8, 482-13, 459) of
      mitochondrial DNA (mtDNA) in formalin-fixed, paraffin-embedded tissue and
      compared with the contractile myocardium. Polymerase chain reaction analysis
      revealed that in the sinus node, the atrioventricular node, and the bundle
      branches, 35 to 40% of total mtDNA molecules harbored the common deletion. In
      contrast, in the contractile myocardium, 10 to 20% of total mtDNA was deleted (P
      = .05). These results demonstrate that in Kearns-Sayre syndrome, the conduction
      system of the heart preferentially accumulates the common deletion. This finding
      might help to explain the high prevalence of cardiac dysrhythmias in this
      syndrome.

PMID- 9521480
TI  - Correspondence re: restoration of Virchow's Pathology Museum at the Charite.

PMID- 9521481
TI  - Characterization of two different Ca2+ entry pathways dependent on depletion of
      internal Ca2+ pools in rat aorta.
AB  - Ryanodine (10 microM), thapsigargin (1 microM) and cyclopiazonic acid (10 microM)
      produced a slow, sustained contractile response in rat aorta that only can be
      observed in Ca2+-containing solution. In Ca2+-free medium, no response to the
      drugs was obtained, which suggests that the contraction elicited in presence of
      Ca2+ is mainly due to the contribution of extracellular influx. This Ca2+ entry
      does not depend on the opening of dihydropyridine-dependent Ca2+-channels for
      nimodipine does not affect this. Noradrenaline (1 microM) induced a biphasic
      response in Ca2+-free medium that was mediated by two different Ca2+
      compartments, one of which is common to caffeine (10 mM), and is also depleted by
      ryanodine (10 microM), thapsigargin (1 microM) and cyclopiazonic acid (10
      microM). This compartment loses its Ca2+ content after long exposure (65 min) to
      Ca2+-free EDTA-containing solution and its refilling was also affected by the
      three agents tested. The other compartment depleted by noradrenaline, but not by
      caffeine, was also insensitive to ryanodine, thapsigargin and cyclopiazonic acid,
      and did not lose its Ca2+ after 65 min in Ca2+-free medium. Contractions induced
      by noradrenaline (1 microM) or caffeine (10 mM) in Ca2+-free medium were not
      affected by ryanodine, thapsigargin and cyclopiazonic acid when these agents were
      added 1 min before or during the response to each agonist. After depletion of
      internal Ca2+ stores sensitive to noradrenaline, an increase in the resting tone
      (IRT) of rat aorta was observed when Ca2+ was added again in absence of the
      agonist. This IRT was not affected by treatment with ryanodine, thapsigargin and
      cyclopiazonic acid, and represents a Ca2+ entry pathway dependent on the
      depletion of the noradrenaline-sensitive Ca2+ compartment. In conclusion, we can
      differentiate two Ca2+ entry pathways in rat aorta that depend on the previous
      depletion of two internal Ca2+ compartments: One corresponds to the classic
      capacitative Ca2+ entry model and is promoted by depletion of the internal pool
      sensitive to noradreanline, caffeine, ryanodine, thapsigargin and cyclopiazonic
      acid, the other is dependent only on depletion of an alpha1-adrenoceptor
      sensitive Ca2+ pool.

PMID- 9521482
TI  - Comparison of human alpha1-adrenoceptor subtype coupling to protein kinase C
      activation and related signalling pathways.
AB  - The coupling of human alpha1-adrenoceptor subtypes to protein kinase C (PKC) and
      PKC-related signalling events were investigated in rat-1 fibroblasts stably
      expressing alpha1A-, alpha1B- or alpha1D-adrenoceptors at densities of 1328+/
      200, 5030+/-703 and 150+/-14 fmol/mg protein respectively. In functional assays
      the alpha1-adrenoceptor agonist phenylephrine significantly stimulated PKC
      (assessed as increased activity in the membrane fraction) in cells expressing
      alpha1A- or alpha1B- but not alpha1D-adrenoceptors. In immunoblot assays phorbol
      ester treatment enhanced membrane-associated immunoreactivity of PKCalpha,
      PKCdelta and PKCepsilon to a similar extent in all three cell lines. Stimulation
      of alpha1A- and alpha1B-adrenoceptors also increased immunoreactivity of
      PKCalpha, PKCdelta and PKCepsilon in the membrane fraction, while alpha1D
      adrenoceptor stimulation yielded only very small and inconsistent alterations.
      Immunoreactivity of PKCzeta was not consistently affected by phorbol ester or
      phenylephrine in any of the cell lines. Stimulation of all three alpha1
      adrenoceptors time- and concentration-dependently increased inositol phosphate
      formation. Maximum activation occurred with the order alpha1A approximately =
      alpha1B > alpha1D. Phenylephrine also concentration dependently elevated free
      intracellular [Ca2+] in all three cell lines with the order of efficacy alpha1A >
      alpha1B > alpha1D. In the presence of ethanol, phenylephrine stimulated
      phosphatidylethanol formation in alpha1A- and alpha1B-adrenoceptor-expressing
      cells time and concentration dependently but only weakly and inconsistently in
      alpha1D-adrenoceptor-expressing cells. The efficacy of phenylephrine (100 microM)
      relative to that of noradrenaline (100 microM) for stimulation of
      phosphatidylethanol formation was similar (> or = 75%) for all three subtypes.
      The alkylating agent phenoxybenzamine concentration dependently reduced alpha1A
      adrenoceptor density and phenylephrine-stimulated Ca2+ elevations to levels seen
      with alpha1D-adrenoceptors but reductions of phenylephrine-stimulated
      phosphatidylethanol formation were weaker. We conclude that human alpha1A- and
      alpha1B-adrenoceptors expressed in rat-1 cells couple to activation of PKCalpha,
      PKCdelta and PKCepsilon but not PKCzeta; this may involve stimulation of
      phospholipases C and D and intracellular Ca2+ elevations. Activation of these
      pathways by alpha1D-adrenoceptors appears to be much weaker and was not detected
      consistently; this was not fully explained by weak partial agonism of
      phenylephrine at this subtype or by lower receptor densities. Overall the alpha1A
      adrenoceptor may have the highest efficiency of stimulus-response coupling among
      human alpha1-adrenoceptor subtypes.

PMID- 9521483
TI  - P2-receptor antagonists: IV. Blockade of P2-receptor subtypes and ecto
      nucleotidases by compounds related to reactive blue 2.
AB  - Effects of reactive blue 2 and twelve structurally related compounds were studied
      on contractions of the rat vas deferens elicited by alpha,beta-methylene ATP
      (alpha,beta-MeATP; mediated by P2X-receptors), relaxations of the carbachol
      precontracted guinea-pig taenia coli elicited by adenosine 5'-O-(2
      thiodiphosphate) (ADPbetaS; mediated by P2Y-receptors), and the degradation of
      ATP by rat vas deferens tissue. All compounds, except acid blue 41 and acid blue
      129 (at up to 100 microM), shifted the concentration-response curve of alpha,beta
      MeATP in the rat vas deferens to the right. Most increased, but uniblue A greatly
      decreased, the maximum of the curve. In the case of cibacron blue 3GA and
      reactive blue 19, of which three concentrations were tested, the Arunlakshana
      Schild regression was linear, and the slope did not differ from unity. The
      apparent Kd values of the effective substances ranged between 0.7 and 111 microM.
      Most compounds increased the contraction of the rat vas deferens elicited by high
      K+. In the guinea-pig taenia coli, all compounds, except uniblue A and reactive
      blue 19 (at up to 100 microM), shifted the concentration-response curve of
      ADPbetaS to the right in a parallel manner. In the case of acid blue 129 and acid
      blue 80, of which three concentrations were tested, the slope of the Arunlakshana
      Schild regression did not differ from unity. The apparent Kd values of the
      effective substances were between 0.7 and 69 microM. Most compounds also reduced
      the relaxation of the guinea-pig taenia coli elicited by noradrenaline. The
      removal of ATP from the medium by vas deferens tissue was decreased only by
      reactive blue 2, cibacron blue 3GA, uniblue A and reactive blue 19, with IC25%
      values between 17 and 62 microM. The structure-activity relationships for P2X-
      and P2Y-receptor blockade in this series are strikingly dissimilar. In reactive
      blue 2 and its isomers, for example, both the 1-amino-anthraquinone-2-sulphonate
      core and the 'side-chain' of the molecule are involved in P2X-receptor binding;
      P2Y-receptor affinity, in contrast, resides largely or totally in the
      anthraquinone core. The most promising antagonists are uniblue A which is P2X-
      versus P2Y-selective and acid blue 129 which is P2Y- versus P2X-selective, both
      with few, if any, non-P2-receptor effects at concentrations blocking the
      respective P2-subtype.

PMID- 9521484
TI  - Role of AT2 receptors in the cardiovascular events following microinjection of
      angiotensin II into the superior colliculus of anaesthetised rats.
AB  - Central injection of angiotensin II (ANGII) induces pressor and regional
      haemodynamic effects. Here we have investigated the systemic and regional
      cardiovascular changes induced by injection of ANGII into the superficial layer
      of the superior colliculus (SC) of male rats anaesthetised with urethane. In
      addition, we have used the AT1 receptor-selective antagonist, losartan, and the
      AT2 receptor-selective antagonist, PD123319 to characterise the receptor(s)
      mediating these effects. Injection of ANGII (0.1, 1 and 100 nmol/rat) into the
      superficial layer of the SC significantly (P < 0.05) increased, in a dose
      dependent manner, the mean arterial blood pressure (MAP) while decreasing the
      heart rate, (e.g. by 37+/-4 beats min(-1), at 1 nmol, P < 0.05). The increases in
      blood pressure induced by ANGII (1 nmol; 43+/-6 mmHg, n = 5) were greatly reduced
      (> 85%) by pre-administration to the SC of PD123319 (50 nmol/rat), but were
      unaffected by losartan (50 nmol/rat). Similarly, PD123319 prevented the decrease
      in heart rate induced by ANGII while losartan did not affect it. Injection of
      ANGII (1 nmol) also increased (P < 0.01) total peripheral resistance (TPR;
      control, 2.36+/-0.1 mmHg ml(-1) min 100 g body weight) by 130+/-10% (n = 5) and
      reduced the cardiac output (CO; control, 99.8+/-1.3 ml min[-1]) by 51+/-3% (n =
      5), as determined by radioactive microspheres. The increase in TPR was associated
      with increases in the vascular resistances of organs, such as the left and right
      kidney (390+/-15%, P < 0.01 and 352+/-12%, P < 0.01 respectively), the skeletal
      muscle (91+/-7%, P < 0.05, n = 5), the stomach (43+/-2%, P < 0.01, n = 5), the
      colon (50+/-3%, P < 0.05, n = 5) and the caecum (65+/-5%, P < 0.05, n = 5). Pre
      treatment of the SC with PD123319 reduced (P < 0.01) the increases in TPR and
      vascular resistance, and the reduction in CO caused by ANGII. Losartan did not
      affect the responses to ANGII. Thus, injection of ANGII into the SC causes
      complex haemodynamic changes which are sensitive to AT2 receptor antagonism. AT2
      receptors are, therefore, the predominant mediators of the actions of ANGII into
      the superior colliculus of the rat.

PMID- 9521485
TI  - The relaxing effect of BDF 9148 on the KCl-contracted aorta isolated from normo-
      and hyper-tensive rats.
AB  - BDF 9148, a positive cardiac inotrope, relaxes the rat isolated portal vein and
      the KCl-contracted rat aorta. The aims of our study were to determine the
      mechanism of action of BDF 9148, and to ascertain whether the relaxing effect of
      BDF 9148 was maintained in the presence of the hypertrophy associated with
      hypertension, by investigating the effects of BDF 9148 on the contractility and
      electrophysiology of aortae of Wistar Kyoto normo-tensive rats (WKY) and
      Spontaneously Hypertensive Rats (SHRs). High concentrations of veratridine
      contracted the quiescent rat aorta. BDF 9148 had no effect on the quiescent, but
      relaxed the KCl-contracted WKY and SHR aorta by a tetrodotoxin insensitive
      mechanism, and these relaxations decreased with age but were not greatly altered
      by hypertrophy. The verapamil relaxations of the KCl-contracted aorta were not
      altered by age or hypertrophy. The ability of KCl to depolarise the aorta was
      reversed by verapamil, but not by BDF 9148. On the contracted rat aorta, the
      relaxant responses to acetylcholine were abolished by removal of the endothelium
      but potentiated by IBMX (10[-6] M), and the responses to isoprenaline were
      inhibited by propranolol (10[-6] M) but potentiated by forskolin (10[-7] M). The
      relaxation responses of the KCl-contracted aorta to BDF 9148 were not altered by
      removal of the endothelium, or by propranolol, forskolin and IBMX. In summary,
      the effects of verapamil and BDF 9148 on the aorta are different, and thus it is
      unlikely that the relaxant responses to BDF 9148 on the aorta are due to calcium
      channel blocking activity. The mechanism of the relaxant effect of BDF 9148 on
      the aorta remains unknown, but we have shown the response is endothelium
      independent, and not mediated by sodium channel opening, hyperpolarization, beta
      adrenoceptors, or by stimulating adenylate cyclase or guanylate cyclase.

PMID- 9521486
TI  - Morphologic and functional consequences of intimal hyperplasia in the rat carotid
      artery.
AB  - The influence of neointima formation on functional characteristics was
      investigated in rat carotid artery preparations. The process of intimal
      hyperplasia development in the injured carotid arteries was followed in time both
      morphologically and morphometrically. Simultaneously with the loss of endothelial
      cells due to the balloon injury procedure, the vasodilator responses to
      methacholine were abolished. The sensitivity for the alpha1-adrenoceptor agonist
      phenylephrine appeared to be increased only immediately after injury. The balloon
      injury method led to significant neointima formation in the rat left common
      carotid artery 14 days after the intervention. Eight weeks after balloon injury,
      the neointimal mass reached its maximum. Parallel to the development of intimal
      hyperplasia, the alpha1-mediated vasoconstrictor responses to phenylephrine were
      significantly impaired. After 12 weeks of observation, reoccurrence of mature
      endothelial cells on the luminal surface of the neointima could be observed.
      Simultaneously, the vascular responses to phenylephrine and methacholine
      recovered. The vasoconstrictor responses to high potassium concentrations (100
      mM) as well as the vasodilator effects of sodium nitroprusside appeared to be
      uninfluenced by balloon injury throughout the period of observation. From this
      study we conclude that both the receptor-mediated contractile responses to alpha1
      adrenoceptor stimulation and the endothelium-dependent vasodilator responses to
      methacholine become severely impaired as a consequence of balloon catheter injury
      followed by intimal hyperplasia. However, these pharmacological responses may
      fully recover upon a prolonged period of endothelial regeneration.

PMID- 9521487
TI  - Differential inhibition of human platelet aggregation and thromboxane A2
      formation by L-arginine in vivo and in vitro.
AB  - We compared the effects of L-arginine (L-ARG), the precursor of endogenous NO, on
      platelet aggregation and thromboxane A2 formation in vivo and in vitro. Human
      platelet-rich plasma (PRP) was anticoagulated with citrate (which decreases
      extracellular Ca2+) or with recombinant hirudin (which does not affect
      extracellular Ca2+). Two groups of 10 healthy male volunteers received
      intravenous infusions of L-ARG (30 g or 6 g, 30 min) or placebo. Blood was
      collected immediately before and at the end of the infusions for aggregation by
      ADP or collagen. Infusion of L-ARG inhibited ADP-induced aggregation in PRP
      anticoagulated with citrate by 37.5+/-6.3% (P < 0.05). In PRP anticoagulated with
      hirudin, aggregation was inhibited by 33.6+/-16.0% (P < 0.05). L-ARG infusion
      also inhibited platelet TXB2 formation and slightly, but not significantly
      decreased the urinary excretion rate of 2,3-dinor-TXB2; cGMP concentrations in
      PRP were significantly elevated during L-arginine infusion. In vitro
      preincubation with L-ARG (10 microM-2.5 mM) inhibited platelet aggregation in PRP
      anticoagulated with rhirudin, but not citrate. This effect was stereospecific for
      L-arginine, as D-arginine had no effect. It was dependent upon NO synthase
      activity, as indicated by increased cGMP levels in PRP. Moreover, both the NOS
      inhibitor L-NMMA and the inhibitor of soluble guanylyl cyclase ODQ antagonized
      the effects of L-ARG. Haemoglobin, an extracellular scavenger of NO, partly
      antagonized the antiplatelet effects of L-ARG. 8-Br-cyclic GMP and the exogenous
      NO donor linsidomine inhibited aggregation in PRP anticoagulated with citrate or
      r-hirudin. The inhibitory effects of L-ARG on platelet aggregation in vitro were
      paralleled by increased cyclic GMP levels; L-ARG also inhibited platelet TXB2
      formation in PRP anticoagulated with r-hirudin, but not citrate. We conclude that
      the L-arginine/NO pathway is present in human platelets as a Ca2+-dependent anti
      aggregatory pathway. In vivo the formation of NO from L-ARG by endothelial cells
      may contribute to the platelet-inhibitory effects of L-ARG. NO-releasing
      compounds like linsidomine inhibit platelet aggregation in vitro independent of
      extracellular Ca2+.

PMID- 9521488
TI  - Differential sensitivity of macrophages to bradykinin.
AB  - In this report, we investigated the responsiveness of subpopulations of elicited
      peritoneal macrophages between each other compared to resident tissue macrophages
      of alveoli of guinea pig to the action of bradykinin. Bradykinin stimulated the
      secretion of superoxide radical, arachidonic acid and prostaglandin E2 (PGE2) via
      the bradykinin B2 receptor subtype in peritoneal macrophages, indicated by
      complete inhibitory effect of the bradykinin B2 receptor antagonist HOE 140. The
      extent of the secretion, however, varied substantially between macrophages of
      different size. The highest level of the secretion was observed in the fraction
      containing the intermediate-size macrophages, while progressively lower level of
      the secretion was observed with decreasing size. In contrast, large macrophages
      obviously lost their secretory ability. Additionally, the bradykinin-stimulated
      release of cyclooxygenase products exerted an inhibitory action on NADPH-oxidase
      activity depending on size and stage of maturation/activation of macrophages, as
      judged by an increase in superoxide radical generation by indomethacin (100
      microM) preincubation of cells. Furthermore, the investigation of resident tissue
      macrophages of alveoli has shown that these cells also express the bradykinin B2
      receptor subtype. However, the receptor activity measured by bradykinin-induced
      increase in intracellular free calcium [Ca2+]i was very low compared to elicited
      peritoneal macrophages. These findings indicate that the stage of
      differentiation/maturation and activation of macrophages may be important for the
      ability of bradykinin to stimulate these cells to inflammatory responses in vivo.

PMID- 9521489
TI  - Peripheral versus central potencies of N-type voltage-sensitive calcium channel
      blockers.
AB  - The ability of a series of synthetic analogues of omega-conopeptides MVIIA (SNX
      111) and TVIA (SNX-185) to prevent electrically-evoked norepinephrine release
      from rat tail artery and hippocampal slice preparations was determined in an
      effort to identify voltage-sensitive calcium channel (VSCC) blockers that
      selectively target N-type VSCCs in central nervous system tissue. Electrical
      field stimulation (3 Hz, 1 ms in duration. 80 V for 1 min) caused a high and
      consistent tritium outflow from rat tail artery and hippocampal slice
      preparations preloaded with [3H]-norepinephrine. All conopeptides, chosen for
      their selective affinities for high-affinity SNX-111 binding sites (i.e., N-type
      VSCCs) over high-affinity omega-conopeptides MVIIC (SNX-230) binding sites (i.e.,
      P/Q-type VSCCs), produced a concentration-dependent inhibition of calcium
      dependent electrically-evoked tritium outflow from both tail arteries and
      hippocampal slices: IC50s ranged from 1.2 nM to 1.2 microM. Blocking potencies
      (IC50s) in the tail artery assay were significantly correlated with those
      measured in the hippocampal slice preparation (r = 0.91, P = 0.00000012). There
      was a significant correlation between IC50s for blockade of hippocampal
      norepinephrine release and the inhibition of high-affinity [125I]-SNX-I11 binding
      in rat brain synaptosomes (r = 0.76, P = 0.00028). Blockade of hippocampal
      norepinephrine release was not significantly correlated with the inhibition of
      high-affinity SNX-230 binding (r = 0.46, P = 0.056). Maximum inhibition of
      tritium outflow in the tail artery assay was 22+/-1.4% of control, approximating
      the value (20.9+/-16.0% of control) obtained in the absence of extracellular
      Ca2+. In contrast, the maximum inhibition of tritium release from hippocampal
      slices was 36.8+/-2.5% of control (P < 0.05, compared to that of the tail artery
      assay). These results suggest that (1) N-type VSCCs alone mediate low frequency
      electrical stimulation-evoked neurotransmitter release from peripheral
      sympathetic efferents (tail artery) while both N-type and non-N type(s) mediate
      neurotransmitter release from CNS neurons (hippocampus); and (2) analogues of
      omega-conopeptides MVIIA and TVIA do not differentiate between N-type VSCCs
      mediating norepinephrine release from central and peripheral neural tissues.

PMID- 9521490
TI  - Influence of catecholamine receptor agonists and antagonists on the ultradian
      rhythm of the EEG in the posterior hypothalamus.
AB  - The power of delta and theta frequency bands of the EEG in the posterior
      hypothalamus of the rat fluctuates according to an ultradian rhythm. To
      investigate, whether catecholamine receptor ligands influence the ultradian EEG
      rhythm, drugs were applied intracerebroventricularly into the lateral ventricle
      of anaesthetized rats. Injection of the alpha1-adrenoceptor agonist (+/-)
      methoxamine (150 nmol) abolished, while 25 nmol of the compound prolonged the
      cycle duration of the rhythmic changes in the delta and theta frequency bands.
      Injected into the lateral ventricle, the alpha2-adrenoceptor agonists 6-ethyl
      5,6,7,8-tetrahydro-4H-oxazol[4,5-d] azepin-2-amine (B-HT 933) or clonidine (150
      nmol each) prolonged the duration of the cycles of both frequency bands. The
      beta1/2-receptor agonists (+/-)-orciprenaline (300 nmol) and (R)-(-)-isoprenaline
      (150 nmol) slowed down the cycle durations of both frequency bands. The beta1
      receptor agonist (+/-)-xamoterol (300 nmol) also prolonged the cycle durations of
      the delta and theta frequency bands. The beta1-receptor antagonist (S)-(-)
      atenolol was ineffective (150 and 300 nmol). The beta2-receptor agonist (+/-)
      salbutamol (300 nmol) shortened the duration of the ultradian rhythm in the two
      frequency bands, while the beta2-receptor antagonist (+/-)-1-[2,3-(dihydro-7
      methyl-1 H-inden-4-yl) oxy]-3-[(1-methylethyl)amino]-2-butanol (ICI 118,551) (300
      nmol) exerted the opposite effect. On the other hand, the D1 receptor agonist (+/
      )-1-phenyl-2,3,4,5-tetrahydro-1H)-3-benzazepine-7,8-diol (SKF 38393) and the D2
      agonist (4aR,8aR)-(-)-quinpirole (150 nmol each) slowed down the frequency of the
      ultradian rhythm. The powers of alpha and beta frequency bands were not
      significantly influenced by the catecholamine receptor ligands used in this
      study. The findings suggest that, in the posterior hypothalamus, the ultradian
      rhythm of the delta and theta frequency bands are prolonged when beta1-receptors
      are stimulated and shortened on stimulation of beta2-adrenoceptors. Endogenous
      catecholamines released from their neurons seem to shorten the duration of the
      rhythmic fluctuations by stimulating beta2-receptors and to slow down the
      frequency of the cyclic fluctuations by stimulating alpha2-adrenoceptors. The
      ultradian rhythm is also slowed down on stimulation of D1 and D2 receptors by
      endogenous dopamine. Together with previous observations, the results indicate
      that the ultradian EEG rhythm is susceptible to modulatory mechanisms mediated by
      catecholaminergic neurons.

PMID- 9521491
TI  - Regulation of nicotinic receptors in the brain of mice withdrawn from chronic
      oral nicotine treatment.
AB  - The effect of nicotine withdrawal on regional regulation of brain nicotinic
      receptors was studied in mice after chronic administration of nicotine in the
      drinking water for 2, 4 or 7 weeks. Two weeks of chronic nicotine administration
      did not alter the binding of [3H]-nicotine in the midbrain, cortex or cerebellum
      of the mice, while after both 4-and 7-week treatments a significant increase in
      the specific [3H]-nicotine binding was observed in cortical and midbrain
      membranes. In the midbrain, the [3H]-nicotine binding was increased by about 40%
      in mice withdrawn for 48-72 h from the 4-week chronic nicotine treatment and in
      mice withdrawn for 48 h from the 7-week treatment. The [3H]-nicotine binding was
      significantly increased (by 55-65%) in the cortex at 48 h and 72 h after
      withdrawal from 4-week chronic nicotine and it was even somewhat more increased
      (by 72-66%) after 7-week treatment. The cortical [3H]-nicotine binding was not
      altered at 24 h after the 4-week treatment, but in mice withdrawn for 24 h from
      the 7-week treatment it was increased by 116%. The increases in [3H]-nicotine
      binding returned to control levels within 1 week after withdrawal. None of the
      studied treatments affected the [3H]-nicotine binding in the cerebellum.
      Tolerance towards nicotine-induced locomotor depression was only found in mice
      withdrawn for 24 h from the 7-week chronic nicotine administration. These
      findings suggest that at least 4-week chronic nicotine administration in the
      drinking water is needed before any upregulation of nicotinic receptors can be
      observed. Furthermore, in our experiments the increase in the [3H]-nicotine
      binding was seen before behavioural tolerance could be demonstrated. The
      differences between brain regions in the time course of nicotinic receptor
      upregulation may reflect variations in nicotinic receptor subunits and their
      sensitivity to chronic nicotine treatment.

PMID- 9521492
TI  - Disruption of the actin cytoskeleton abolishes high affinity 3H-glibenclamide
      binding in rat aortic rings.
AB  - The interaction between the cytoskeleton and the ATP-sensitive K+ channel (KATP
      channel) was studied in rat aortic rings by examining the binding of the
      sulphonylurea blocker, 3H-glibenclamide, and of the opener, 3H-P1075. The actin
      cytoskeleton disrupting agents, cytochalasin D (1 microM) and latrunculin B (1
      microM), abolished the high affinity component of 3H-glibenclamide binding.
      Preincubation with the actin cytoskeleton stabilizing agent, phalloidin (10
      microM) prevented the effect of cytochalasin D. In contrast, binding of the
      opener, 3H-P1075, and inhibition of this binding by glibenclamide, were
      unaffected by cytochalasin D (3 microM). Colchicine (100 microM), which
      disassembles microtubules, had no effect on the binding of 3H-glibenclamide and
      3H-P1075. The data show that high affinity binding of glibenclamide, which
      mediates the effects of the sulphonylurea in this preparation, requires the
      presence of an intact actin cytoskeleton. Binding of the opener is unaffected by
      the state of the cytoskeleton and preserves a conformational state in which high
      affinity binding of glibenclamide to the sulphonylurea receptor can occur.

PMID- 9521493
TI  - Differential age-dependent expression of alpha2 adrenoceptor- and P2 purinoceptor
      functions in rat locus coeruleus neurons.
AB  - Whole-cell patch clamp recordings were made in a pontine slice preparation of the
      rat brain containing the nucleus locus coeruleus (LC). In a first series of
      experiments, it was demonstrated that tyrosine hydroxylase-positive LC neurons of
      young (10-14 days of age) rats are multipolar with numerous dendrites. When
      pipettes filled with the marker molecule biocytin were used for recording, all
      cells exhibiting outward current responses to noradrenaline (100 microM) showed
      the morphology typical for LC neurons. At a holding potential of -80 mV,
      noradrenaline (100 microM) produced a comparably small outward current both in LC
      neurons of young (8-14 days) and older (18-23 days) rats. In contrast, 2
      methylthio ATP (2-MeSATP; 100 microM) caused a relatively small inward current in
      the young animals, while inward current responses were much larger in most older
      animals (8 out of a total of 11). It is suggested that after birth there are
      probably no functional P2 purinoceptors present at LC neurons. Thereafter, P2
      purinoceptor-function increases with age, reaching maturity only in animals older
      than 18 days.

PMID- 9521494
TI  - Phorbol 12-myristate 13-acetate can transform monocyte-derived dendritic cells to
      different cell types similar to those found in dermatofibroma. A possible in
      vitro model of the histogenesis of dermatofibroma.
AB  - Dermatofibroma is composed largely of interlacing fascicles of slender spindle
      cells set within a loose collagenous stroma and of scattered foamy histiocytes
      and multinucleated giant cells. There is clear evidence indicating that factor
      XIIIa+ dermal dendritic cells (DDCs) are the cells constituting dermatofibromas.
      However, it is still unknown what stimulation is responsible for transforming
      DDCs into different cell types, producing different subtypes of dermatofibromas.
      Recently, it has become possible to obtain dendritic cells (DCs), that are
      identical with DDCs in their phenotypic and functional characteristics, from the
      culture of CD14+ peripheral blood monocytes to which IL-4 and GM-CSF were added.
      Using these monocyte-derived DCs, we examined the ability of various cytokines,
      such as IL-1beta , IL-3, IL-5, IL-6, IL-7, IL-8, IL-10, TNFalpha, TGFbeta, M-CSF,
      IFNalpha, and IFNgamma, and phorbol 12-myristate 13-acetate (PMA), to induce
      different cell types observed in DFs. Among them, only PMA could induce a variety
      of cell types such as histiocytic cells, fibroblastic spindle-shaped cells, and
      even multinucleated giant cells of Touton or foreign body type. Phenotypically,
      all the induced cell types expressed CD1a, CD80, CD86, HLA-DR, and CD68 in a
      magnitude similar to that of non-treated monocyte-derived DCs. The expression of
      factor XIIIa was strongest in histiocytic cells, moderate in fibroblastic cells,
      and weakest or negative in giant cells. These data suggest that dermatofibromas
      are a kind of neoplastic disease which is induced only by the effect of some
      tumor promoter on DDCs.

PMID- 9521495
TI  - The interstitial granulomatous drug reaction: a distinctive clinical and
      pathological entity.
AB  - We present 20 patients in whom drug therapy was associated with interstitial
      histiocytic infiltrates with variable degeneration of collagen and elastic fibers
      mimicking early lesions of granuloma annulare (GA). Most patients had a
      reproducible clinical presentation comprising erythematous-to-violaceous,
      nonpruritic plaques, often with an annular pattern, predominantly involving inner
      aspects of the arms, medial thighs and intertriginous areas. The most frequent
      clinical differential diagnoses included cutaneous T cell lymphoma, erythema
      annulare centrifigum (EAC), GA, and lupus erythematosus. A drug reaction was
      suspected in only 3 cases. The implicated drug classes included calcium channel
      blockers, angiotensin converting enzyme inhibitors, beta-blockers, lipid-lowering
      agents, antihistamines, anticonvulsants and antidepressants. Patients were often
      on two or more of these drugs; all have been associated with pseudolymphomatous
      infiltrates of the skin, the presumptive basis of which is iatrogenic pertubation
      of immune function. The defining histomorphology was diffuse infiltration of the
      interstitium by lymphocytes and histiocytes with piecemeal fragmentation of
      collagen and elastic fibers in concert with a vacuolar interface dermatitis. Ten
      cases showed intermediate and transformed lymphocytes with hyperchromatic
      convoluted nuclei disposed interstitially within the dermis or along the
      dermoepiderma junction with variable epidermotropism. In the 15 patients who
      discontinued the implicated drug, lesional resolution occurred. We propose the
      designations interstitial granulomatous drug reaction for this novel cutaneous
      reaction pattern.

PMID- 9521496
TI  - Intraepidermal lymphocytes in psoriatic lesions are activated GMP-17(TIA
      1)+CD8+CD3+ CTLs as determined by phenotypic analysis.
AB  - The onset and persistence of psoriatic lesions are linked to the presence of an
      inflammatory infiltrate of CD3+ lymphocytes that includes CD4+ and CD8+ subsets.
      Since a primary susceptibility factor for psoriasis is the Class I HLA-Cw6
      molecule, we set out to learn more about the features of the epidermal CD8+
      lymphocytes. The markers tested were GMP-17, a cytotoxic granule protein found in
      activated cytotoxic lymphocytes (CTLs), and the alpha chain of the IL-2 receptor
      (CD25), a plasma membrane molecule found on activated T cells. Lymphocytes in
      lesional skin expressed the GMP-17 protein, whereas lymphocytes in non-lesional
      skin, resolving lesional skin and normal skin had little or no GMP-17. By flow
      cytometry analysis, lesional epidermal GMP-17+ cells were CD8+CD3+, with a
      subpopulation expressing the activation marker CD25+. Due to the abundance of
      activated GMP-17+CD8+CD3+ lymphocytes (the phenotype of activated cytotoxic
      cells) in psoriatic lesions compared to non-lesional and normal skin, we
      hypothesize that they are contributing directly to the psoriatic phenotype.

PMID- 9521497
TI  - Effects of topical calcipotriol on the expression of adhesion molecules in
      psoriasis.
AB  - Seven patients with chronic plaque psoriasis were treated with topical
      calcipotriol for 8 to 24 weeks; the lesions improved in 5 patients.
      Immunohistochemistry was performed on frozen sections, to evaluate the expression
      of adhesion molecules and extracellular matrix components before and after
      therapy. Changes in expression and topography of beta1 and beta4 integrins were
      found on psoriatic lesions before therapy and a reduction in the expression of
      tenascin was detected as well. Moreover, several activation markers such as ICAM
      1, HLA-DR, CD26 were focally positive, with a diffuse cytoplasmic reactivity, in
      basal and suprabasal layers in untreated lesions. In the 5 patients in whom
      lesions regressed after topical calcipotriol treatment, we observed a
      histological normalization of the epidermis and the inflammatory infiltrate was
      reduced. Moreover, not only was there a normalization in the expression and
      topography of adhesion molecules, but also the integrin pattern observed after
      therapy was superimposable to that of normal skin.

PMID- 9521498
TI  - Nodular post-kala-azar dermal leishmaniasis: a distinct histopathological entity.
AB  - Post-kala-azar dermal leishmaniasis (PKDL) is an infrequently occurring sequel to
      treated visceral leishmaniasis. Diagnosis, particularly in non-endemic areas, is
      difficult because the clinical appearances may be subtle and simulate lepromatous
      leprosy. The histopathology of the condition has been a neglected subject.
      Nodular lesions constitute one of the large variety of lesions that can be seen
      in PKDL. This paper describes the histopathology of such lesions in 26 patients
      seen over a period of approximately 8 years in a non-endemic setting. All the
      biopsies had strikingly similar light microscopic features with characteristic
      findings: a dense lymphohistiocytic infiltrate beneath an atrophic epidermis,
      pronounced follicular plugging, vascular hyalinization and collagen changes and
      negative Fite stain. These allow a definite diagnosis of PKDL even in the absence
      of demonstrable Leishman-Donovan (L-D) bodies.

PMID- 9521499
TI  - Staining of eccrine and apocrine neoplasms and metastatic adenocarcinoma with IKH
      4, a monoclonal antibody specific for the eccrine gland.
AB  - The histogenesis of apocrine and eccrine neoplasms has always interested
      dermatopathologists. In addition, the histologic differential diagnosis of
      eccrine carcinoma from metastatic adenocarcinoma is of practical importance. We
      describe a novel monoclonal antibody IKH-4 which stains the eccrine secretory
      coil, but not the apocrine secretory segment. Positive staining was observed in
      eccrine hidradenoma, eccrine poroma, eccrine spiradenoma, papillary eccrine
      adenoma, eccrine hidrocystoma, syringoma, eccrine carcinoma, and in 1 case of
      syringocystadenoma papilliferum. Negative staining was observed in apocrine
      adenocarcinoma, hidradenoma papilliferum, erosive adenomatosis of the nipple, and
      primary and metastatic adenocarcinomas. IKH-4 antibody was useful in
      differentiating eccrine from apocrine neoplasms and in differentiating eccrine
      carcinoma from metastatic adenocarcinomas.

PMID- 9521501
TI  - Collodion baby and lamellar ichthyosis.
AB  - It is important to differentiate the collodion baby from harlequin ichthyosis as
      the latter rarely survives past the first few days of life. Occasionally, babies
      share features of both disorders and defy a clinical diagnosis. We recently
      encountered such a baby who initially presented with harlequin-like features, but
      evolved into lamellar ichthyosis once the keratin cast was shed. Since the
      routine histology of all these ichthyoses is similar, we used electron microscopy
      to study serial biopsy specimens from the affected infant on days 7, 14, and 150,
      and compared them to our own other cases of harlequin ichthyosis and lamellar
      ichthyosis. Electron microscopic studies of our case revealed that the marginal
      band of cornified cells of the stratum corneum was absent when the baby exhibited
      collodion/harlequin ichthyosis features. Another biopsy taken when the clinical
      picture evolved into lamellar-like ichthyosis, showed a well-formed marginal band
      in the cornified cells. In harlequin ichthyosis, the marginal band is present at
      birth. It is suggested that electron microscopy can differentiate severe
      collodion baby from harlequin ichthyosis at birth using the absence of the
      marginal band. Previously reported features of harlequin ichthyosis, such as the
      presence of giant mitochondria and an abnormal formation of the marginal band in
      luminal villi of acrosyringeal eccrine duct, were absent in our case.

PMID- 9521500
TI  - Ultrastructural localization of cell junctional components (desmoglein,
      plakoglobin, E-cadherin, and beta-catenin) in Hailey-Hailey disease, Darier's
      disease, and pemphigus vulgaris.
AB  - The distribution of desmoglein, plakoglobin, E-cadherin, and beta-catenin in the
      peri-lesional and lesional skin of Hailey-Hailey disease, Darier's disease, and
      pemphigus vulgaris was examined by immunoelectron microscopy. In the peri
      lesional skin, the immunolabeling of these desmosomal components was localized to
      desmosomes. Adherens junction-associated E-cadherin and beta-catenin were at the
      cell periphery, excluding desmosomes. The labeling pattern was similar among
      these diseases, but the labeling intensity particularly that of plakoglobin in
      Hailey-Hailey disease and Darier's disease, was less than that of normal
      controls, suggesting that these glycoproteins are quantitatively less
      concentrated in the normal epidermis of these inherited diseases. In the
      acantholytic cells of Hailey-Hailey disease and Darier's disease the
      immunolabeling of the components of desmosomes was diffusely distributed in the
      cytoplasms, whereas that of adherensjunction was mostly at the cell periphery and
      partly diffusely in the cytoplasm. In contrast, desmosomes of detaching
      keratinocytes in pemphigus vulgaris still showed the labeling of desmoglein and
      plakoglobin. These findings suggest that the inherited acantholytic diseases,
      i.e., Hailey-Hailey disease and Darier's disease have a different pathogenesis
      from that of autoimmune acantholysis in pemphigus vulgaris: The intracellular
      components of desmosomes may primarily be disrupted in the genetic acantholytic
      diseases in the initial stages of acantholysis. Several unsolved questions in the
      previous light microscopic immunofluorescence studies using the same antibodies
      are now answered: 1) the diffusion of desmosomal proteins is not due to the
      internalization of desmosomes, 2) intracellular components of adherens junction
      are also finally dissolved, 3) diffuse cytoplasmic immunofluorescence patterns of
      desmosomal components could be explained by immunoelectron microscopy as those
      attached to cell membrane and trapped in tonofilament aggregates.

PMID- 9521502
TI  - CD34-positive eruptive fibromas.
AB  - The list of entities comprising a proliferation of CD34 (+) spindle cells
      continues to grow. Described, herein, is a patient who had an indolent eruption
      of scattered papules composed of CD34 (+) spindle cells, beginning in
      adolescence. An 18-year-old female patient presented with asymptomatic, tan/brown
      papules over the neck, chest, and proximal extremities. They appeared 6 years
      previously and had slowly increased in number. Biopsy from the neck showed a
      proliferation of plump spindle cells, associated with delicate collagen, in the
      upper reticular dermis. No atypia nor mitotic figures were present. The spindle
      cells were negative for S-100, muscle actins, and Factor XIIIa, but stained
      intensely with CD34. This unusual mesenchymal proliferation of CD34 (+) apparent
      dermal dendrocytes did not have the storiform pattern, short fascicles, nor
      mitotic figures of DFSP. The completely negative muscle markers helped to exclude
      dermatomyofibroma, and no morphological evidence of vasoformative differentiation
      was seen. The clinical picture militated against solitary fibrous tumor. These
      eruptive tumors are benign and thought to represent a distinctive fibroma
      produced by proliferated CD34 (+) stromal cells.

PMID- 9521503
TI  - Papillary "apocrine" fibroadenoma of the vulva.

PMID- 9521504
TI  - What's new in ovarian serous borderline tumors.

PMID- 9521505
TI  - Factor XIIIa expression in granulomatous lesions due to sarcoidosis or
      mycobacterial infection.
AB  - The a-subunit of the clotting factor XIII (FXIIIa) has previously been shown to
      be synthesized by cells of monocyte lineage such as macrophages and histiocytes.
      Thus, besides clot retraction, a possible role of FXIIIa has also been postulated
      in inflammation. In order to test this hypothesis, FXIIIa-expression in
      granulomatous lesions due to sarcoidosis and mycobacterial infection was
      investigated. In the 12 cases (six cases each) examined, FXIIIa-positive
      macrophages were consistently detected by immunohistochemistry. They were
      predominantly observed in the periphery of granulomas, whereas the centers were
      generally devoid of these cells. We did not find any difference in the
      distribution of FXIIIa-positive cells in both conditions; thus FXIIIa did not
      improve the differential diagnosis between sarcoidosis and tuberculosis. However,
      FXIIIa-producing macrophages seemed to contribute to the centripetal fibrosis in
      granuloma. These results further suggest that the basic pathogenetic mechanisms
      in granuloma formation are very similar, regardless of their origin from
      sarcoidosis or tuberculosis.

PMID- 9521506
TI  - Expression of biglycan, decorin and proteoglycan-100/CSF-1 in normal and fibrotic
      human liver.
AB  - The immunohistochemical expression of the three small chondroitin/dermatan
      sulphate proteoglycans biglycan, decorin and proteoglycan-100 (PG-100), the
      proteoglycan form of colony-stimulating factor-1 (CSF-1), was studied in normal
      and fibrotic human liver. In normal liver tissue biglycan and decorin were
      clearly seen in the space of Disse, which was in contrast to a faint staining of
      PG-100. Biglycan and decorin were additionally detected around small bile ducts
      and in vessel walls. In patients with HBs-Ag positive, chronic active hepatitis
      decorin as well as biglycan showed strong immunoreactivity in fibrotic areas. In
      contrast to normal liver, PG-100 was visualized in bile duct epithelia.
      Therefore, PG-100 could serve as an immunohistochemical marker of the involvement
      of the bile duct system in chronic active hepatitis and progressive liver
      fibrosis.

PMID- 9521507
TI  - Immunohistochemical analysis of apocrine breast lesions. Consistent over
      expression of androgen receptor accompanied by the loss of estrogen and
      progesterone receptors in apocrine metaplasia and apocrine carcinoma in situ.
AB  - Apocrine phenotype is observed in a spectrum of breast epithelial lesions
      spanning from benign metaplasias to apocrine carcinoma. Apocrine metaplasia is a
      common finding in fibrocystic change of the female breast. In situ and invasive
      apocrine carcinomas are rare variants of ductal carcinoma. All breast apocrine
      lesions were shown to be associated with increased androgen hormones metabolism.
      We have evaluated 10 cases of apocrine metaplasia, 3 cases of in situ apocrine
      carcinoma and 10 cases of invasive apocrine carcinomas using immunostaining
      method for steroid hormone receptors (estrogen, progesterone, androgen), p53, bcl
      2 and BRST-2. Paraffin embedded tissue and avidin-biotin peroxidase complex
      system were used. Androgen receptor (AR) expression is consistently increased in
      all cases of apocrine metaplasia when compared with surrounding normal, non
      apocrine breast epithelium. This androgen receptor over-expression is accompanied
      by the loss of immuno-detectable estrogen and progesterone receptor, and also the
      loss of bcl-2. An identical pattern of immuno-reactivity is seen in in situ
      apocrine carcinomas, but it is observed with less frequency in invasive apocrine
      carcinomas, which only infrequently express AR as the only steroid hormone
      receptor.

PMID- 9521508
TI  - Malignant mesothelioma of the pleura. The reproducibility of the
      immunohistological diagnosis.
AB  - The reproducibility of the histopathological diagnosis of pleural malignant
      mesothelioma (MM), after supplementing routine H&E stain by immunohistochemistry
      (IH) in 77 cases of original diagnoses of MM, was assessed by examining
      interobserver variation between five pathologists. A battery of commercial
      antibodies (cytokeratins, vimentin, HMFG-2, anti Leu-M1 [CD15], BerEP4, B72.3
      [TAG-72], carcinoembyonic antigen), considered to be useful in enhancing
      diagnostic accuracy, was used. The number of definitively classified tumors
      (accepted MM plus rejected MM) increased from 57 on H&E stain to 60 after IH,
      with 59 (76.6%) cases being accepted as true MM. Based on IH, the chance-adjusted
      interobserver agreement was poor (kappa w = 0.29) and lower than that observed on
      previous H&E alone. The intraobserver agreement for four of the five pathologists
      was rather good (kappa w = 0.54-0.56). The inter- and intraobserver concordance
      was higher in accepting than excluding the cases as MM. A larger number of cases
      were classified by all reviewers as mixed or sarcomatous variants after IH. In
      the interpretation of each immunostain, kappa values ranged from 0.19 for B72.3
      to 0.62 for HMFG-2, which were respectively the least and the most consistently
      interpreted immunostains. The information additionally contributed by IH did not
      seem to change the pathologists' diagnoses very much in comparison with those
      made by routine H&E stain. Until highly specific and sensitive probes for the
      positive identification of MM become available, a careful scrutiny of routinely
      stained preparations still remains the most rewarding component of the diagnostic
      pathway.

PMID- 9521509
TI  - The role of p53, MDM2 and c-erb B-2 oncoproteins, epidermal growth factor
      receptor and proliferation markers in the prognosis of urinary bladder cancer.
AB  - The immunohistological expression of p53 and MDM2 oncoproteins was examined in
      paraffin embedded tissue from 106 patients with transitional cell carcinoma of
      the urinary bladder and was related to various clinicopathological features, the
      expression of proliferation associated markers (proliferating cell nuclear
      antigen - PCNA - and Ki-67), c-erb B-2 oncoprotein and epidermal growth factor
      receptor (EGFR), as well as to survival. MDM2 immunoreactivity was seen in 38% of
      our cases, and in 14% was accompanied by p53 positive immunohistochemistry. The
      rate of p53 positivity was associated with grade, stage and papillary status,
      whereas MDM2 immunopositivity increased with grade and stage (Ta VS T1), and MDM2
      labeling index (LI) with stage. MDM2 expression was related to p53 expression and
      less strongly to proliferation rate (Ki-67 LI). The simultaneous p53 and MDM2
      expression was more frequently observed in higher grade and stage tumours. C-erb
      B-2, EGFR and proliferation marker expression increased with grade, stage and non
      papillary configuration. In univariate analysis high grade, solid growth pattern,
      advanced T-category, cystectomy, EGFR and Ki-67 expression were linked to shorter
      overall survival but only Ki-67 LI, along with T-category and type of therapy,
      had independent prognostic value. C-erb B-2 expression and stage were the two
      independent predictors of disease-free survival and Ki-67 LI and EGFR LI the
      independent predictors of post-relapse survival. For patients with superficial
      tumors PCNA LI emerged as the single independent determinator of survival. p53
      and MDM2 expression did not appear to have any significant impact on survival,
      although the simultaneous expression of p53 and MDM2 turned out to be a highly
      significant parameter of shortened overall survival in univariate analysis.

PMID- 9521510
TI  - Intrathyroidal lymphoepithelial cyst. A report of two cases not associated with
      Hashimoto's thyroiditis.
AB  - Two cases of intrathyroidal lymphoepithelial cyst are described. Both of them
      were solitary, one being found incidentally in a patient operated on for a
      multinodular goiter, the other being clinically obvious as a cold nodule. They
      exhibited features of cysts of branchial cleft origin, i.e. squamous cell lining
      epithelium and abundant lymphoid tissue with reactive germinal centers. The
      thyroid gland parenchyma showed a discrete lymphoid infiltration consistent with
      the diagnosis of focal lymphocytic thyroiditis. In the first case a single
      epidermoid solid cell nest was found. The histogenesis of intrathyroidal
      lymphoepithelial cysts remains unclear, but their origin from cystically
      degenerated ultimobranchial body remnants (solid cell nests) seems to be most
      probable. This assumption is supported by a similar immunohistochemical profile
      of solid cell nests and epithelial cells lining the cysts and also by the
      presence of one solid cell nest in the proximity to the cyst in one of our cases.

PMID- 9521511
TI  - Gestational squamous cell carcinoma of the breast: an unusual mammary tumor
      associated with aggressive clinical course.
AB  - We report two cases of squamous carcinoma of the breast detected during the
      gestational period. One woman was post-partum and lactating; one was in the first
      trimester of pregnancy. The lesions were clinically palpable, multifocal, and
      measured more than 5 cm in their largest dimension; both had a cystic appearance.
      They were treated with radical mastectomy. One patient received pre-operatory
      chemotherapy. Histologically, the tumors were poorly differentiated squamous cell
      carcinomas. No areas of ordinary duct differentiation were seen. Lymph nodes
      contained metastatic squamous carcinoma in both cases. Tumor cells were negative
      for estrogen and progesterone receptors. Also, they expressed a high
      proliferative index and several markers of tumor progression, including cErb-B2,
      p53 protein, bcl-2, and epidermal growth factor receptor. One patient died of
      tumor 5 months following breast surgery and had extensive metastases proven at
      autopsy. The other patient had evidence of pulmonary metastases: following
      cisplatin therapy, she underwent clinical remission. This study shows that
      squamous carcinoma of the breast may occur in pregnant or lactating women: it
      appears clinically distinguishable from the non-gestational type that is usually
      associated with a better prognosis and occurs in peri- or postmenopausal women.

PMID- 9521512
TI  - Primary intrathyroidal paraganglioma with metachronous carotid body tumor: report
      of a case and review of the literature.
AB  - A case of primary intrathyroidal paraganglioma is reported, and the light
      microscopic and immunohistochemical findings are described. Primary
      paragangliomas of the thyroid region are extremely uncommon and are therefore
      often confused clinically and histopathologically with more common intrathyroidal
      mass lesions. The diagnostic difficulties are underscored by the present case,
      which was misdiagnosed twice, firstly as a medullary thyroid carcinoma and
      secondly as a follicular thyroid carcinoma. Immunohistochemistry may be very
      helpful in arriving at the correct diagnosis. The case was further complicated by
      a second neck mass contralateral to the original thyroid nodule, which was
      interpreted as consistent with metastasis. The second lesions was proved
      angiographically and histologically to be a carotid body paraganglioma.

PMID- 9521514
TI  - Is suction drainage necessary after total joint arthroplasty? A prospective
      study.
AB  - A prospective evaluation of 98 patients who had undergone a total hip or knee
      arthroplasty was conducted to assess the effect of postoperative suction
      drainage. Sixty-six patients undergoing elective total hip arthroplasty and 32
      patients undergoing total knee replacement were randomly allocated to undergo
      either suction drainage or no drainage of the wound. Statistical analysis of the
      results showed no difference in wound healing, severity of wound haematoma,
      postoperative blood transfusion requirement, range of motion and duration of the
      hospitalization between the two groups. We conclude that the use of closed
      suction drainage provides no apparent advantage after uncomplicated total hip or
      knee arthroplasty.

PMID- 9521513
TI  - Well differentiated gastric adenocarcinoma with rhabdoid areas: a case report
      with immunohistochemical analysis.
AB  - We describe the case of a 73-year-old patient with gastric adenocarcinoma
      composed of histologically well differentiated glandular areas, extensive
      rhabdoid zones and regions depicting a transition between these two constituents.
      The rhabdoid component showed typical features such as abundant eosinophilic
      cytoplasm, eccentric nuclei, prominent nucleoli, intense positive
      immunohistochemical cytoplasmic reaction for vimentin and less evident
      immunohistochemical for cytokeratin and epithelial membrane antigen (EMA). Our
      findings strongly suggest that the rhabdoid areas probably represent a phenotypic
      variant of a gastric adenocarcinoma, otherwise fairly well differentiated, a
      combination that to the best of our knowledge has not been previously reported.

PMID- 9521515
TI  - Revisions of endoprosthetic reconstructions after limb salvage in musculoskeletal
      oncology.
AB  - Of 91 limb-salvage procedures using prosthetic reconstructions because of primary
      or metastatic bone and soft-tissue tumors 26 revisions were performed in 16
      patients. Revision was due to polyethylene wear (9 cases), aseptic loosening (8
      cases), recurrent hip dislocation (3 cases), prosthetic stem fracture (2 cases),
      infection (2 cases), leg length discrepancy (1 case), and traumatic dislocation
      of a saddle prosthesis (1 case). The follow-up period for tumor control varied
      from 1.5 to 22 years with a median of 13.5 years. The follow-up period after the
      last revision operation varied from 0.5 to 12 years with a median of 3 years. At
      the last follow-up, the functional results had deteriorated compared with after
      the primary operation in 5 patients and had improved in 2 patients. In the
      remaining patients, the results did not change.

PMID- 9521516
TI  - The Furlong hydroxyapatite-coated femoral prosthesis. A 4- to 7-year follow-up
      study.
AB  - We report the clinical and radiograph outcome of 77 Furlong hydroxyapatite fully
      coated femoral prosthesis in 71 patients undergoing primary total hip
      replacement, with mean follow-up of 65 months (range 48-82 months). The patients'
      average age at surgery was 55 years. The clinical results, as determined by
      Harris hip score, were excellent or good for 84% of the hips. Thigh pain which
      was not disturbing was present in 9% of the hips. No femoral component had been
      revised for aseptic loosening, and none were considered loose radiographically at
      the time of final follow-up evaluation. Serial radiographs revealed an excellent
      quality of bone around the prostheses, with positive evidence of bone ingrowth
      and no signs of impending failure.

PMID- 9521517
TI  - Osteoclastic differentiation by mononuclear phagocytes containing biomaterial
      particles.
AB  - Aseptic loosening of implant components is a common and important complication of
      both cemented and uncemented prosthetic joint replacements. Wear particles
      derived from organic polymer and metal implant biomaterials are commonly found
      within macrophages and macrophage polykaryons in the fibrous membrane between
      loose implant components and the host bone undergoing resorption. In order to
      determine whether biomaterial particle-containing, foreign-body macrophages may
      contribute to periprosthetic bone resorption, we cultured murine monocytes that
      had phagocytosed particles of biomaterials commonly employed in bone implant
      surgery [polymethylmethacrylate (PMMA), ultra-high molecular weight polyethylene
      (PE), titanium and chromium-cobalt] on bone slices and glass coverslips with UMR
      106 osteoblast-like stromal cells in the presence of 1,25-dihydroxy-vitamin D3.
      Under these conditions, all biomaterial particle-containing, foreign-body
      macrophages differentiated into osteoclastic cells, i.e. tartrate-resistant acid
      phosphatase (TRAP)-positive multinucleated cells capable of extensive lacunar
      bone resorption. This study shows that particle phagocytosis by macrophages does
      not abrogate the ability of these cells to undergo osteoclast differentiation.
      These findings emphasise the importance of the foreign-body macrophage response
      to biomaterial wear particles in the pathogenesis of aseptic loosening.

PMID- 9521518
TI  - Synthesis of articular cartilage-like tissue in vitro.
AB  - Defects in mature articular cartilage do not heal without residues, and therefore
      they remain a challenging problem in orthopaedic surgery. Modern tissue culture
      techniques facilitate the synthesis of cartilage-like tissue. A requirement of
      retaining the phenotypic characteristics of chondrocytes in vitro is the use of
      three-dimensional culture techniques. Articular chondrocytes of adult rabbits
      were isolated and cultured on different transplantable media for several weeks. A
      resorbable fleece, a non-absorbable net and lyophilized dura were used. Viability
      was tested by immunohistochemical techniques. Deposition of extracellular matrix
      could be observed by electron microscopy. The phenotypical and morphological
      appearance of cultured chondrocytes was preserved on the resorbable polymer
      fleece and the lyophilized dura. Cells cultured on the non-absorbable net had a
      more fibroblastic appearance. The resorbable fleece is apparently most suitable
      in terms of viability of the cultured chondrocytes and biocompatibility. The
      cultured three-dimensional artificial cartilage constructs reveal a future
      possibility for autologous cartilage transplantation into mature cartilage
      defects.

PMID- 9521519
TI  - A new mechanical aiming device for the placement of distal interlocking screws in
      femoral nails.
AB  - Although the free-hand technique remains the most popular method for distal
      interlocking screw insertion, a proximally mounted "radiation-independent" device
      which compensates for implant deformation has been developed. In 15 intact human
      cadaveric femora the same surgeon performed statically locked intramedullary
      nailing using the distal aiming system. Operation time, distal screw insertion,
      total radiation time and accuracy of the interlocking screw placement were
      measured using a radiation-independent distal aiming system. The average total
      operation time was 21.2+/-8.6 min, and the average distal locking time (2 screws)
      was 7.1+/-2.4 min. The total operation time and the distal locking time declined
      over the first 10 cases. These times did not significantly improve in the
      subsequent 5 procedures. The average total fluoroscopy time was 28.1+/-16.6 s.
      None of the screw placements using the distal aiming device required the use of
      fluoroscopy. Drill-nail contact was absent in 5 drillings, mild in 9 drillings,
      moderate in 16 drillings, and severe in none. Measurement of screw damage showed
      in 55 of 60 measurements wear of less than 15 microm. There were no failures or
      major complications. A minor complication related to distal locking was observed
      in one specimen. This study suggests that distal interlocking screws can be
      placed successfully using a radiation-independent aiming arm-based system, which
      accounts for nail deformations. The distal aiming device (DAD) can be learned
      easily. The main advantages of the aiming arm include the elimination of
      radiation during distal interlocking and precise screw placement with little
      insertion-related hardware damage.

PMID- 9521520
TI  - Femoral nerve lesion in total hip replacement: an experimental study.
AB  - A total of 20 hip joints of 10 non-fixed corpses were examined within 48 h of
      death to measure the pressure below the inguinal ligament simulating the surgical
      conditions during total hip arthroplasty. The purpose of this study was to assess
      the influence of various leg positions and insertion techniques of retractors
      during the surgical procedure for total hip replacement in order to detect
      supposed causes for indirect pressure injuries of the femoral nerve. The obtained
      results verified no increase of pressure in the inguinal canal which could
      explain an indirect injury of the femoral nerve. If the retractor is inserted
      correctly at the anterior acetabular rim, the pressure in the lacuna musculorum
      can even be reduced, and furthermore, the femoral nerve is protected by the
      iliopsoas muscle. Femoral nerve lesions which have been published so far can only
      be explained by an incorrect use of instruments or implants (e.g., screws,
      cement, acetabular cup) or an extreme postoperative leg length discrepancy.

PMID- 9521521
TI  - Topical hyperbaric oxygen and low energy laser for the treatment of diabetic foot
      ulcers.
AB  - Fifty patients with chronic diabetic foot ulcers in whom conventional therapy had
      failed were treated with topical hyperbaric oxygen alone (15 patients) or in
      combination with a low energy laser (35 patients). Eleven of these patients were
      treated on an ambulatory basis with topical hyperbaric oxygen. The mean time the
      ulcer was present before therapy was 9+/-6.6 months. The mean number of
      treatments was 25+/-13, and the mean duration of therapy was 3+/-1.8 months.
      Forty-three of the 50 patients were cured. No adverse reactions were noted. Our
      impression is that topical hyperbaric oxygen alone or in combination with a low
      power laser are valuable adjuvants to conventional therapy for diabetic foot
      ulcers.

PMID- 9521522
TI  - Redisplacement after ankle osteosynthesis with absorbable implants.
AB  - A total of 1202 fractures of the ankle were treated with absorbable implants made
      of polyglycolide/polylactide copolymer or self-reinforced polyglycolide and/or
      self-reinforced polylactide between November 5, 1984, and January 12, 1994. A
      redisplacement after fixation was diagnosed in 30 patients (2.5%). The
      redisplacement occurred in 8 of 934 (0.9%) simple ankle fractures and in 22 of
      268 (8.2%) severer ankle fractures. A breakage or loosening of the absorbable
      implant was verified at reoperation in 8 cases and was suspected in another 9. A
      technical failure was the main reason in 13 cases. A reoperation was performed
      for 25 patients. The absorbable implants seem to provide a secure fixation in the
      majority of ankle fractures, but the use of these implants showed unsatisfactory
      results in unstable and comminuted fractures.

PMID- 9521523
TI  - Different radiological approaches to preoperative estimation of implant stability
      in vertebral bodies.
AB  - The present investigation studied whether or not ventral derotation spondylodesis
      (VDS) screw fixation strength can be estimated preoperatively by means of
      radiology. Furthermore, comparison of the techniques applied was done to show
      which of them is most appropriate. The bone mineral density of human cadaveric
      lumbovertebral bodies was assessed by both dual-energy X-ray absorptiometry (DXA)
      and quantitative computed tomography (QCT). Trabecular structure was
      characterised by T2*-relaxation time magnetic resonance imaging (MRI). After
      ventral instrumentation of vertebral bodies with VDS screws, their axial pullout
      force was assessed as a reference value for initial stability of the implant.
      Data from each radiological method were correlated with it. The highest
      correlation with pullout force was registered for density of cancellous bone by
      QCT (r = 0.72; P > 0.001), immediately followed by DXA (r = 0.70; P < 0.001). T2*
      relaxation time (MRI) correlated moderately (r = 0.55), whereas cortical bone
      density (QCT) showed a negligible correlation (r = 0.2). Results reveal that
      absorptiometrical techniques like DXA and QCT (cancellous bone) are the most
      appropriate ones to assess initial screw fixation strength in vertebral bodies
      preoperatively.

PMID- 9521524
TI  - Aneurysm of a persistent sciatic artery.
AB  - We report a case of an aneurysm of a persistent sciatic artery which caused
      buttock pain. Preoperative diagnosis is very difficult. However, awareness of the
      presence of this rare embryonic abnormality is important, especially in elderly
      persons with atherosclerotic changes. Sagittal magnetic resonance imaging (MRI)
      was very useful in reaching this diagnosis.

PMID- 9521525
TI  - Histology of the femur after cancellous impaction grafting using a Charnley
      prosthesis.
AB  - We report the histologic findings of a retrieved femur 6 months after a cemented
      hip revision with a Charnley standard prosthesis and impaction of morselized
      allograft. Most transplanted areas were revascularised. In the proximal femur
      there was new bone formation peripherally, but a substantial amount of fibrous
      stroma embedding graft pieces closer to the cement. In the diaphysis new bone
      formation had proceeded to within less than 0.5 mm of the cement.

PMID- 9521526
TI  - Fracture of the hamate hook presenting as median nerve palsy.
AB  - We report a case of fracture of the hamate hook presenting as median nerve palsy
      and discuss the etiology of this rarely seen complication. We consider that the
      median nerve palsy in this case was due to direct nerve compression within the
      carpal tunnel caused by a displaced fractured hook fragment.

PMID- 9521527
TI  - Enhancing screw stability in osteosynthesis with hydroxyapatite granules.
AB  - We employed hydroxyapatite (HA) granules to enhance screw fixation in revision
      surgery of failed osteosynthesis with a compression hip screw system in an 83
      year-old woman. After reduction of the fracture, the fracture site with a large
      bone defect was filled with HA granules, and osteosynthesis was accomplished with
      a double cannulated lag screw and plate system. We feel that this HA granule
      augmentation method may also be suitable for osteosynthesis in other osteoporotic
      fractures.

PMID- 9521529
TI  - A new method for treating isolated fractures of the os trapezium.
AB  - Isolated trapezium fractures are rare events. As standard radiographic methods
      may fail to diagnose this injury, specific radiographic projections are needed to
      separate the outline of the trapezium from the other carpal bones. Computed
      tomography can be helpful in visualizing the true shape of fragments. In this
      report a vertical and transversal isolated fracture of the trapezium was repaired
      by using the dynamic Herbert compression screw technique. Open reduction and
      internal fixation resulted in union with excellent thumb function and joint
      restoration. A report of this case and the special technique of treatment is
      combined with a discussion of literature.

PMID- 9521528
TI  - Bilateral piriformis syndrome after total hip arthroplasty.
AB  - We present the case of a 39-year-old man with bilateral piriformis syndrome 4 and
      6 years after two cementless total hip arthroplasties, respectively. During
      surgical exploration, each sciatic nerve was found to be entrapped by a tense
      piriformis muscle and hypertrophic posterior hip capsule. The sciatic-type pain
      was relieved after sectioning each piriformis muscle with external neurolysis.
      This is the first reported case of piriformis syndrome after total hip
      arthroplasty.

PMID- 9521530
TI  - Modulation of mRNA expression of the neurotrophins of the nerve growth factor
      family and their receptors in the septum and hippocampus of rats after transient
      postnatal thyroxine treatment. I. Expression of nerve growth factor, brain
      derived neurotrophic factor, neurotrophin-3, and neurotrophin 4 mRNA.
AB  - Early postnatal application of thyroid hormones to rats results in morphological
      changes in septum and hippocampus. Modulation in the expression of either
      neurotrophins and/or their receptors is postulated to be responsible for these
      effects. In the present study we tested whether thyroxine administration leads to
      changes in the expression of neurotrophins of the nerve growth factor (NGF)
      family. Newborn rats were treated daily with subcutaneous injections of thyroxine
      until postnatal day (P) 12 at maximum. The pups were killed at defined intervals
      from P2 to 21. The septal area and the hippocampi were analyzed using the reverse
      transcriptase-PCR method for quantitation of NGF, brain-derived neurotrophic
      factor (BDNF), NT-3, and NT-4 messenger RNA (mRNA) levels. In hippocampus of
      hyperthyroid rats, as compared to controls, we found higher levels of BDNF and NT
      3 mRNA over the total investigation period, whereas in the septum a thyroxine
      dependent increase in NT-3 mRNA expression was observed. In addition, significant
      thyroxine-induced effects were found for all variables (except for NGF in the
      septum) at particular postnatal days. From these data we conclude that modulation
      of neurotrophin expression is a possible mechanism for the morphological
      modifications within the hippocampal mossy fiber system and the septohippocampal
      cholinergic system.

PMID- 9521531
TI  - The influence of initial hand posture on the expression of prehension parameters.
AB  - This paper describes the transport and grasp kinematic parameters associated with
      four initial hand postures (palm flat and thumb against the hand, palm flat and
      thumb extended laterally, index and thumb in opposition, and index and thumb in
      opposition and elbow flexed 90 degrees). A group of healthy adult subjects
      reached for and picked up a wooden dowel placed midsagittally, at one of three
      distances (20 cm, 25 cm and 30 cm). The initial posture of the hand and arm
      altered transport (peak velocity and peak negative acceleration) as well as grasp
      (peak angle and time to peak angle) parameters, particularly when the elbow was
      flexed 90 degrees. The pattern of results was reproduced in a pointing paradigm.
      The findings are discussed in the context of joint space models of reaching.

PMID- 9521532
TI  - Audiovocal behavior of Doppler-shift compensation in the horseshoe bat survives
      bilateral lesion of the paralemniscal tegmental area.
AB  - The role of the paralemniscal tegmental area of the horseshoe bat, Rhinolophus
      rouxi, in the control of vocalization and Doppler-shift compensation was
      investigated using electrical and pharmacological stimulation and lesioning
      techniques. The paralemniscal tegmental area is situated in the dorsolateral
      tegmentum ventral to the inferior colliculus and rostral and medial to the dorsal
      and intermediate nuclei of the lateral lemniscus. Vocalizations indistinguishable
      from spontaneously uttered calls can be elicited with both electrical and
      pharmacological stimulation methods, demonstrating that the stimulation of neural
      elements within the area and not fibers passing through the area are responsible
      for the stimulated call emission. The audiovocal feedback system for Doppler
      shift compensation was also investigated. Doppler-shift compensation adjusts the
      frequency of the emitted calls according to the increases in the frequency of the
      echoes that are normally encountered in flying bats. Bats compensate for Doppler
      shifts not only under natural conditions but also when echoes are played back to
      the bat following spontaneous vocalizations or vocalizations induced by
      electrical or pharmacological stimulation of the investigated brain area.
      Unilateral electrolytic lesions of the paralemniscal tegmental area did not
      impair the ability to evoke vocalizations with electrical stimulation of the
      unlesioned side. The calls had exactly the same structure and frequency
      composition as those emitted prior to lesioning. Unilateral lesions also did not
      impair Doppler-shift compensation performance. After bilateral lesioning of the
      paralemniscal area, vocalizations could not be evoked with electrical
      stimulation. However, normal calls were emitted spontaneously and Doppler-shift
      compensation during spontaneous call emission was unaltered compared with the
      intact condition. The paralemniscal tegmental area is therefore not an audiovocal
      feedback system required for Doppler-shift compensation, but rather a brain area
      whose stimulation and activation is sufficient but not necessary for call
      emission. It is also not directly involved in the control of spectral parameters
      of vocalization but contributes to the control of the occurrence of vocal output.

PMID- 9521533
TI  - Motor unit discharge and force tremor in skill- and strength-trained individuals.
AB  - We examined motor unit (MU) discharge properties (mean interspike interval, ISI,
      discharge variability, short-term synchronization, common drive) and force tremor
      in the first dorsal interosseous (FDI) muscle of five musicians (skill-trained),
      five weight-lifters (strength-trained) and six untrained subjects during low
      force isometric abduction of the index finger. Mean MU ISI was slightly shorter
      in skill-trained subjects than in untrained subjects. Discharge variability of
      FDI MUs did not differ significantly between groups. The mean strength of MU
      synchronization (expressed as the frequency of extra synchronous discharges above
      chance) was different in skill-trained (0.22+/-0.02 s(-1), 162 MU pairs),
      untrained (0.32+/-0.02 s(-1), 199 MU pairs) and strength-trained subjects (0.44+/
      0.03 s(-1), 183 MU pairs). FDI MU synchrony was weak and of equivalent strength
      in both hands of skill-trained subjects and the dominant (skilled) hand of
      untrained subjects. The stronger FDI MU synchrony in the non-dominant hand of
      untrained subjects was equivalent to that found in both hands of strength-trained
      subjects. The extent of common modulation of firing rates (common drive) was
      assessed for a subset of MU pairs and was weaker in skill-trained subjects
      (0.30+/-0.04, n=14) than untrained (0.43+/-0.3, n=14) and strength-trained
      (0.48+/-0.03, n=21) subjects. Force tremor was quantified for each hand in the
      same subjects during isometric index finger abduction at target forces of 0.5 N
      and 3.5 N. Tremor rms amplitude and peak power in the force frequency spectrum
      were significantly lower in skill-trained subjects than strength-trained subjects
      with the 3.5-N target force. The peak tremor frequency was similar in the three
      groups. The relatively more independent discharge of pairs of FDI MUs in skill
      trained subjects was not responsible for the reduced tremor amplitudes in these
      subjects. Correlations between the overall extent of MU synchrony and common
      drive in FDI muscles and tremor measures obtained during the same experimental
      session were all non-significant. Differences in the central descending command
      signals are the most likely explanation for the more independent discharge of FDI
      MUs in skill-trained hands, while neural or peripheral muscular factors may be
      responsible for the weaker tremor.

PMID- 9521534
TI  - Indications for coupling between feline spinocervical tract neurones and
      midlumbar interneurones.
AB  - The possibility of collateral segmental actions of spinocervical tract (SCT)
      neurones upon interneurones with input from cutaneous and group II muscle
      afferents was investigated in deeply anaesthetized cats. To this end,
      intracellular and/or extracellular recordings were made from 35 dorsal horn and
      15 intermediate zone interneurones in midlumbar segments of the spinal cord and
      effects of stimulation of the ipsilateral dorso-lateral funiculus (DLF) at C3 and
      C1 levels, i.e. below and above the lateral cervical nucleus where axons of SCT
      cells terminate, were compared. The stimuli applied at the C3 segment were within
      the range of stimuli (50-100 microA) required for antidromic activation of SCT
      neurones in the same experiment. Those applied at the C segment (200-500 microA)
      were at least 3 times stronger than C3 stimuli. Under the same experimental
      conditions, long ascending and descending tract neurones (dorsal spino-cerebellar
      and rubro-spinal tract neurones) with axons in the DLF were activated at similar
      thresholds from the C and C3 segments. Intracellular recordings were made from 29
      interneurones of which 19 (65%) were dorsal horn and 10 (35%) were intermediate
      zone interneurones. Excitatory postsynaptic potentials (EPSPs) evoked by single
      stimuli applied at the C3 segment, but not the C segment, were found in 14 (48%)
      of those interneurones; their latencies (3.0-5.7 ms) and frequency following with
      only minimal temporal facilitation were as required for potentials being evoked
      monosynaptically by the fastest conducting SCT neurones. Extracellular recordings
      were made from 30 interneurones (24 dorsal horn and 6 intermediate zone
      interneurones), and in these neurones spike potentials induced from the C3, but
      not from the C segment, were evoked only by short trains of stimuli. However,
      their latencies from the first effective stimulus (4.3-5.4 ms) were compatible
      with mono- or oligosynaptically mediated collateral actions of SCT neurones. They
      were found in 10 (33%) of the 30 investigated interneurones. Similar effects of
      C3 stimuli were found in similar proportions of dorsal horn interneurones and
      intermediate zone interneurones. Indications were also found for synaptic actions
      evoked by C3 stimuli that could not be attributed to direct collateral actions of
      SCT neurones. In some intracellularly recorded dorsal horn interneurones, short
      latency EPSPs were evoked from the C3 segment by the 2nd or 3rd stimulus in the
      train, but not by single stimuli. In other dorsal horn and intermediate zone
      interneurones, inhibitory postsynaptic potentials (IPSPs) were evoked from the C3
      segment at minimal latencies (2.7-3.2 ms), which might be too short to allow
      their mediation via SCT neurones. We conclude that SCT neurones might be used to
      forward information from muscle group II and cutaneous afferents not only to
      neurones in the lateral cervical nucleus and via them to thalamus and cerebral
      cortex but also to interneurones in spinal reflex pathways. Thereby reflex
      actions evoked from group II and cutaneous afferents might be co-ordinated with
      responses mediated by supraspinal neurones. We conclude also that dorsal horn and
      intermediate zone mid-lumbar interneurones might contribute to the previously
      reported di-and poly-synaptic excitation or inhibition of postsynaptic dorsal
      column (PSDC), spinothalamic tract (STT) and spinomesencephalic tract (SMT)
      neurones by collateral actions of SCT cells. Thereby these interneurones might
      contribute to the co-ordination of responses mediated by various populations of
      supraspinal neurones.

PMID- 9521535
TI  - Subcellular localization of low-affinity nerve growth factor receptor
      immunoreactive protein in adult rat purkinje cells following traumatic injury.
AB  - Cerebellar Purkinje cells in the rat express low-affinity nerve growth factor
      receptor (p75 NGFR) antigen during development, but rarely in normal adult
      animals. In striking contrast, re-expression of p75 NGFR-immunoreactive protein
      was reported by light microscopy immunocytochemistry in adult rat Purkinje cells
      as early as 1 day after traumatic axotomy. Characteristically, varicose axons
      through the infraganglionic zone were also stained. To date, however, there is no
      information on the subcellular location of the antigenic re-expression. To
      address this, a pre-embedding immunocytochemical ultrastructural study using
      affinity-purified monoclonal 192-IgG was carried out after an experimentally
      induced traumatic lesion of the rat cerebellum. At the electron microscopic
      level, immunostaining was intense in Purkinje cells. In these cells, the
      immunoreactivity was always associated with the internal face of the membranes of
      the rough endoplasmic reticulum, Golgi apparatus and nuclear envelope. Patches of
      immunoreactivity were also associated with the outer surface of the plasma
      membrane of the cell body, dendritic processes and axons. It is noteworthy that
      receptor immunoreactivity was detected in recurrent collaterals of Purkinje cell
      axons forming symmetric synaptic contacts with the cell body and dendrites of
      immunonegative local circuit neurons. Results of this study show that injury
      induced re-expression of p75 NGFR antigen is restricted to Purkinje cells. Also,
      the relative importance of the contribution of the local circuit neurons to the
      production of neurotrophic substances after trauma is suggested.

PMID- 9521536
TI  - Role of proprioceptive information in the temporal coordination between joints.
AB  - Ten subjects made rapid, simultaneous movements of jaw (elevation or lowering)
      and right foot (ankle flexion or extension) in two experimental situations: (1)
      in response to an external signal (reaction-time situation), and (2) in a self
      paced situation. We calculated the mean time intervals between the onsets of
      electromyographic (EMG) activity of agonist muscles (tibialis anterior or
      gastrocnemius lateralis compared with masseter or digastricus pars anterior) and
      those between the onsets of movement acceleration at each joint. Despite the fact
      that subjects reported simultaneous jaw-foot movements, there was always a short
      time interval between the two movements as between the agonist EMG activities.
      When the subjects were asked to perform a jaw elevation movement simultaneously
      with an ankle movement (flexion or extension), the sign of the time interval was
      dependent on the situation of movement initiation. In the reaction-time
      situation, the jaw motor activity preceded that of the ankle, whereas the reverse
      temporal order was observed in the self-paced situation. This is consistent with
      a previous hypothesis suggesting that the simultaneity of two motor actions is
      centrally established through two separate central processes: reactive or
      predictive. When subjects tried to perform simultaneous jaw lowering and foot
      flexion or extension movements, the strict temporal order observed when
      considering jaw elevation and ankle movements disappeared. The jaw motor activity
      generally preceded that of ankle in the reactive situation, but, depending on the
      subjects, it preceded or followed the ankle motor activity during self-paced
      movements. It is likely that the specific spindle supply of jaw muscles accounts
      for these results. Indeed, the jaw depressor muscles, in contrast to the
      elevators, lack muscle spindles. Our results suggest that the kinesthetic inputs
      used by the upper central nervous system to synchronize two rapid voluntary
      movements are mainly those from spindles located in the muscles that accelerate
      the movement, suggesting a strong alpha-gamma linkage.

PMID- 9521537
TI  - Dual (excitatory and inhibitory) calretinin innervation of AMPA receptor
      containing neurons in the rat lateral septum.
AB  - A recent study demonstrated both an extrinsic and an intrinsic calretinin (CR)
      innervation of the rat septal complex and that a population of the extrinsic
      calretinin fibers is aspartate/glutamate-containing. The aim of this study was to
      determine which types (GluR1, GluR2/3, or both) of AMPA receptor-containing
      lateral septal area neurons are innervated by extrinsic and intrinsic CR neurons
      and whether the intrinsic CR cells are GABAergic. Light- and electron-microscopic
      single immunostaining for CR, GluR1, and GluR2/3, as well as light- and electron
      microscopic-double immunostaining experiments for CR plus GluR1 and CR plus
      GluR2/3 were performed in the lateral septal area. Furthermore, the "mirror"
      colocalization technique was employed on consecutive vibratome sections of the
      septal complex to investigate whether the intrinsic septal CR neurons are
      GABAergic. The results are summarized as follows: (1) both GluR1- and GluR2/3
      immunoreactive neurons are innervated by CR-containing fibers; (2) the majority
      of these synapses, observed mainly on the soma and, to a lesser extent, on
      proximal dendrites of AMPA receptor-containing neurons, represent asymmetric
      synaptic membrane specializations; (3) a minority of CR-containing axon terminals
      associated with both GluR1- and GluR2/3-immunoreactive neurons form symmetric
      contacts, predominantly on their soma; and (4) 93% of the lateral septal area CR
      cells are GABAergic. These observations indicate that both GluR1- and GluR2/3
      containing lateral septal area neurons receive a dual intrinsic and extrinsic CR
      innervation. The former (intrinsic) CR boutons are GABAergic, while the latter
      form asymmetric synaptic contacts, are excitatory, and probably originate in the
      supramammillary area, since previous work has demonstrated that a population of
      supramammillo-septal fibers contain aspartate and/or glutamate.

PMID- 9521538
TI  - Perturbed step initiation in cerebellar subjects. 1. Modifications of postural
      responses.
AB  - Recent experiments in healthy subjects have demonstrated that automatic postural
      responses can be suppressed when subjects are instructed to step instead of
      maintain stance in response to the surface translation. The aim of the present
      study was to investigate the role of the cerebellum in coordinating this
      interaction between the central command to step and peripherally triggered
      automatic postural responses. Eight subjects with cerebellar degeneration and
      eight control subjects were instructed to either maintain stance or step forward
      in response to a backward translation. In order to determine whether prediction
      of perturbation amplitude assisted suppression of postural responses, three
      platform translations were presented in both a serial (predictable) and a random
      (unpredictable) order. Cerebellar subjects were able to suppress their initial
      postural responses to the same amount as control subjects when instructed to step
      forward in response to backward translations, despite their hypermetria and
      inability to scale responses to predictable perturbation amplitudes. Control, but
      not cerebellar, subjects scaled the size of their postural responses to
      predictable perturbation amplitudes. The perturbation amplitude, however, had no
      effect on the size of early automatic responses when they were suppressed by
      instruction to step. The size of the suppressed postural response was independent
      of predictability of perturbation amplitudes in both control and cerebellar
      subjects. The dynamic interaction between automatic postural responses to an
      external perturbation and anticipatory postural adjustments for step initiation
      seems independent of prediction of perturbation amplitude and the integrity of
      the cerebellum. Although cerebellar subjects show larger-than-normal magnitude
      and variability of postural responses and an inability to scale the size of
      responses to predictable perturbation amplitudes, the cerebellum does not seem to
      be critical for suppression of the early postural response with a centrally
      intended movement.

PMID- 9521539
TI  - Localisation of arginine vasopressin V1a receptors on sympatho-adrenal
      preganglionic neurones.
AB  - Vasopressin-containing nerve terminals are present in the spinal cord of several
      species. This study was designed to determine whether sympatho-adrenal
      preganglionic neurones (SPN) express vasopressin receptors (VPRs). SPN in the
      spinal cord were revealed by retrograde labelling of Fluorogold following its
      unilateral injection into the adrenal medulla of 12-20 day postnatal rats. VPRs
      were simultaneously visualised in the Fluorogold-labelled slices of spinal cord
      using a recently developed biotinylated vasopressin receptor antagonist [1
      phenylacetyl,2-O-methyl-D-tyrosine,6-arginine,8-arginine,9-lysinam ide(Nepsilon
      biotinamidocaproamide)]vasopressin, PhAcAL(Btn)VP. The VPR:PhAcAL(Btn)VP
      complexes were visualised either with Texas Red-conjugated avidin or with a
      Vectastain avidin:alkaline phosphatase detection kit. These dual-labelling
      experiments revealed VPRs to be present in the spinal grey matter and to be
      particularly dense in the intermediate grey matter and adjacent regions of the
      ventral horn. Many SPN were associated with receptor-specific labelling of
      PhAcAL(Btn)VP, thereby demonstrating that VPRs are expressed by these neurones.
      These VPRs were pharmacologically defined as the V1a subtype. It is concluded
      that sympatho-adrenal preganglionic neurones express VPRs and that these are of
      the V1a subtype. The distribution of VPRs is not, however, restricted to these
      SPN in the spinal cord.

PMID- 9521540
TI  - Monocular and binocular control of human interceptive movements.
AB  - Previous work in our laboratory has demonstrated that binocular vision makes an
      important contribution to skilled reaching and grasping movements directed at
      static targets. In the present study we examine the contribution of binocular
      vision to interceptive reaching movements. We monitored such movements using a
      high-resolution, opto-electronic recording device (WATSMART), while subjects
      attempted to catch balls projected at them. No differences were found between
      monocular and binocular viewing conditions using this paradigm - either with
      respect to the velocity profiles or trajectories of the reaches. Moreover, the
      grasp was not affected by the type of vision available. It appears, then, that
      the moving targets provide adequate monocular depth and direction information (on
      the basis of optic flow) for the control of skilled interceptive movements
      directed at them. In addition, the time to achieve maximum grip aperture was
      constant across the trials - a finding consistent with the use of a time-to
      contact variable derived from optic flow information. Finally, the transport
      component of prehension was found to be affected by certain variables that have,
      in the past, been thought to exclusively affect the grasp component of
      prehension, whereas the grasp component of prehension was affected by factors
      that have traditionally been thought to affect only the transport component.

PMID- 9521541
TI  - Comparative study of event-related potentials and positron emission tomography
      activation during a paired-associate memory paradigm.
AB  - Event-related potentials (ERP) and regional cerebral blood flow (rCBF) activation
      using 15O-labeled water associated with retrieval and retention of episodic
      memory were studied during a visual paired-association task with delayed response
      in eight healthy subjects. In both studies, the subjects memorized four pairs of
      figures during the learning period. They were presented with each cue (S1) and
      asked to judge whether the following figure (S2) formed one of the memorized
      pairs. In an attempt to identify brain activity related to memory function, a
      choice reaction task with delay was used as a behavioral control. The ERP study
      showed a posterior positive component in the difference waveform, which was
      obtained by subtracting responses in the choice reaction task from those in the
      paired association task, between 300 and 850 ms after S1 presentation. It was
      maximal at the parietal midline electrode and distributed predominantly over the
      left posterior quadrant of the scalp. The rCBF activation study showed a greater
      increase in rCBF in the right dorsolateral prefrontal cortex (Brodmann's area
      46), left inferior frontal cortex (Brodmann's area 44/45), left thalamus, and
      bilateral cerebellar hemisphere during the paired association task as compared to
      the choice reaction task, which suggests a possible involvement of cerebello
      thalamo-cortical circuit in the memory processing. Additionally, it is suggested
      that the scalp distribution of the ERP component may not necessarily represent
      regional cortical activation below the electrodes where such a component is
      observed and could indirectly represent activation in remote areas such as
      subcortical regions. It seems that ERP and rCBF activation may provide
      information about different aspects of higher brain function.

PMID- 9521542
TI  - Contribution of vestibular nerve irregular afferents to viewing distance-related
      changes in the vestibulo-ocular reflex.
AB  - The contribution of irregular vestibular afferents to viewing distance-related
      changes in the angular vestibulo-ocular reflex (AVOR) and combined angular and
      linear VOR (CVOR) was studied in squirrel monkeys trained to fixate earth
      stationary targets that were near (10 cm) and distant (90-170 cm) from their
      eyes. Perilymphatic anodal galvanic currents were used to reversibly silence
      irregular vestibular afferents for periods of 4-5 s during the AVOR and CVOR
      evoked by 0.5- to 4-Hz sinusoidal rotations (6-20 degrees/s peak velocity) or 250
      400 degrees/s2 acceleration steps. The direction and magnitude of linear
      translation were changed by positioning the monkeys at different distances off
      the axis of turntable rotation. The effects of irregular afferent galvanic
      ablation (GA) on viewing distance-related changes in the AVOR were studied in
      four animals. Viewing distance-related changes in the AVOR could not always be
      evoked and were frequently small in amplitude. GA reduced viewing distance
      related change in the AVOR by an average of 64% when it was present. Thus
      vestibular irregular afferents appear to play an important and necessary role in
      viewing distance-related changes in the AVOR - on those occasions when the
      changes occur. Viewing distance-related changes in the CVOR were large and
      reliably evoked. GA had very little effect on the gain or phase of viewing
      distance-related changes in the CVOR, although the viewing distance-related CVOR
      responses of individual central vestibular neurons were affected. We conclude
      that irregular afferents probably contribute to central signal processing related
      to both the AVOR and the CVOR, but the signals carried by these afferents are
      only essential for viewing distance-related changes in AVOR.

PMID- 9521543
TI  - Mapping episodic memory.
AB  - This paper presents an analysis of brain regions generally associated with a
      frequently used episodic memory task; visual word recognition. The results from
      five positron emission tomography studies of regional cerebral blood flow,
      involving a total of nine pairwise comparisons of brain activity related to
      episodic retrieval and to performance on non-episodic reference tasks, were
      considered. Across studies, increased activity has been observed in the right
      anterior and posterior prefrontal, anterior cingulate, bilateral parietal, and
      cerebellar regions. Decreased activity has been found in bilateral temporal and
      left midfrontal regions. Comparison of this activation pattern with those of
      other memory tasks, episodic and semantic, indicate that the right anterior and
      posterior prefrontal regions guide processes selectively demanded by episodic
      memory retrieval. There is suggestive evidence from subtraction analyses that
      these prefrontal regions are activated by different processing components, and
      analyses of functional connectivity provide further support for functional
      differentiation. These analyses also point to a critical role of medial-temporal
      brain regions in episodic retrieval. Taken together, these results show that
      episodic memory retrieval is mediated by an extensive set of brain regions, some
      of which seem to be specifically engaged by episodic remembering.

PMID- 9521544
TI  - Electrical self-stimulation in the central amygdaloid nucleus after ibotenic acid
      lesion of the lateral hypothalamus.
AB  - This experiment was carried out in order to investigate the involvement of
      lateral hypothalamus (LH) in electrical self-stimulation of the central
      amygdaloid nucleus (CeA). Adult male Sprague-Dawley rats were bilaterally
      implanted with a guide cannula situated above each LH and with two electrodes in
      the CeA. Self-stimulation was subsequently obtained separately from both right
      and left electrodes. The LH was then lesioned unilaterally by ibotenic acid (IBO)
      injection. Eight days later, the effect of this unilateral lesion on self
      stimulation of the ipsilateral and contralateral CeA was tested. Then the neurons
      of the remaining non-lesioned LH side were lesioned with IBO and self-stimulation
      was tested 15 days after the second lesion. Both unilateral as well as bilateral
      lesions of LH produced a significant decrease in CeA self-stimulation rates but
      had no significant effect on the reward effectiveness. The unilateral lesions did
      not produce any modification of the rate-intensity function in the contralateral
      CeA. This lesion-induced depression in performance was reversed by treatment with
      phenobarbital. These results provide clear evidence that the rewarding effects of
      CeA electrical stimulation do not result from the activation of the LH outputs
      and that the apparent decrease in CeA self-stimulation may result from the LH
      lesion-induced increase in the frequency of epileptiform manifestations that
      occur following amygdaloid stimulation.

PMID- 9521545
TI  - Regional brain changes in [3H]SCH 23390 binding to dopamine D1, receptors after
      long-term haloperidol treatment: lack of correspondence with the development of
      vacuous chewing movements.
AB  - Localized alterations in brain D1 receptors have been suggested to play a role in
      the development of vacuous chewing movements (VCMs) in rodents after long-term
      neuroleptic treatment. In the present study [3H]SCH 23390 binding to D1 receptors
      in basal ganglia and other brain regions was examined in rats showing high or low
      VCM levels after 21 weeks of treatment with haloperidol decanoate (HAL). D1
      binding was significantly decreased in the caudate-putamen of HAL-treated rats,
      compared with vehicle-treated controls (- 18%, P < 0.001). However, this decrease
      occurred equally in treated rats showing high or low levels of VCMs. No changes
      were observed in any other brain region examined, including various subdivisions
      of the substantia nigra pars reticulata. D1/D2 binding ratios were significantly
      decreased in HAL-treated as compared to vehicle controls in all regions examined,
      with the exception of the olfactory tubercle. However, no differences in D1/D2
      ratios between high VCM and low VCM subgroups were detected. Correlations between
      frequency of VCMs and D1 binding, D2 binding or D1/D2 binding ratios across brain
      regions were generally modest (< 0.5). These results confirm the ability of long
      term haloperidol to induce selective decreases in D1 binding in specific brain
      areas, but fail to provide evidence for a possible role of altered D1 receptor
      binding in the development of oral dyskinetic syndromes after long-term
      neuroleptic treatment.

PMID- 9521546
TI  - Protective effects of fetal neocortical transplants on cognitive function and
      neuron size in rats with congenital micrencephaly.
AB  - The rat with micrencephaly, produced by prenatal exposure to methylazoxymethanol,
      provides a useful model to study neurobehavioral abnormalities associated with
      congenital brain defects. The micrencephalic animals have a life-long learning
      impairment. As they age, their already impaired learning competence deteriorates
      further. To determine whether the aging-associated functional deterioration could
      be ameliorated by a neural transplant, micrencephalic rats bearing solid
      transplants of normal fetal neocortical tissue since infancy were evaluated on a
      visual pattern discrimination learning at 15 months and a spatial navigation test
      at 24 months of age. The transplant-bearing rats learned both tasks significantly
      better than the micrencephalic rats without transplants. Morphometric analyses
      revealed that cortical pyramidal neurons were larger in the transplant-bearing
      rats than in micrencephalic rats without transplants. The life-long presence of a
      transplant appeared to have protected the micrencephalic brain against aging
      associated deterioration. This is the first demonstration that a neural
      transplant, placed in a congenitally defective infant brain, can ameliorate aging
      associated cognitive deficits.

PMID- 9521547
TI  - NMDA-coupled periaqueductal gray glycine receptors modulate anxioselective drug
      effects on plus-maze performance.
AB  - The present study was carried out to investigate a possible interaction between
      the effects of anxiety modulating drugs which act at the GABA-A receptor complex
      and selective N-methyl-D-aspartic acid (NMDA) coupled glycine receptor (GLY-B
      receptor) ligands within the dorsal periaqueductal gray (DPAG). The plus-maze
      performance of rats pretreated with diazepam (0.37 and 0.75 mg/kg, i.p.) or
      pentylenetetrazole (15 and 30 mg/kg, i.p.), standard anxiolytic and anxiogenic
      drugs respectively, was assessed following intra-periaqueductal injections of
      either glycine (0.2 M, 0.4 microl/30 s, i.c.) or its competitive antagonist, 7
      chlorokynurenic acid (7ClKYN, 0.02 M, 0.4 microl/30 s, i.c.). Whilst diazepam
      produced a typical anxiolytic effect in intracranially-injected CSF rats,
      increasing open arm exploration, pentylenetetrazole displayed an opposite
      anxiogenic profile. Either anxiogenic or anxiolytic effects were seen in
      peripherally-injected vehicle rats following intra-periaqueductal injections of
      glycine or 7ClKYN, respectively. Intra-periaqueductal injection of glycine
      markedly attenuated the anxiolytic effect of diazepam. Moreover, while the
      anxiogenic effects of pentylenetetrazole were barely changed by glycine, they
      were markedly attenuated by intra-periaqueductal injection of 7ClKYN. Interaction
      of diazepam and 7ClKYN produced non-selective sedative-like effects which masked
      any possible anxiolytic action. Accordingly, the present results suggest that the
      NMDA-coupled glycine receptors located in the DPAG interfere with anxioselective
      effects of GABA-A acting drugs on the elevated plus-maze. In spite of the
      prevailing notion that the NMDA coupled glycine receptor is saturated at in vivo
      brain concentrations of glycine, our results also suggest that either unoccupied
      or low-affinity GLY-B receptors are likely to be activated by glycine injection
      into DPAG.

PMID- 9521548
TI  - Judgements of visual precedence by strabismics.
AB  - Strabismus induced early in the life of cats results in disruption of the normal
      development of the posterior corpus callosum. In human strabismic amblyopic
      subjects a similar disruption in callosal development may cause poor
      interhemispheric integration of simple visual information. To examine this
      possibility judgements of visual target onset precedence were made for targets
      presented in bilateral and unilateral viewing conditions using a method of
      constants psychophysical procedure. In one condition, with targets presented in
      opposite visual fields requiring integration between the two hemispheres, the
      subjects having strabismic amblyopia had significantly larger just noticeable
      difference values (JNDs) than those found for the non-strabismic controls. In a
      second condition, with targets presented within a visual field requiring
      integration within only a single hemisphere, the JNDs for the two groups were not
      significantly different. The results suggest that strabismic amblyopes have poor
      integration of visual information between the cerebral hemispheres, and that this
      reflects disruptions in the development of the posterior corpus callosum.

PMID- 9521549
TI  - Cardiovascular and somatic startle and defense: concordant and discordant actions
      of benzodiazepine receptor agonists and inverse agonists.
AB  - Benzodiazepine receptor (BZR) agonists and inverse agonists yield generally
      opposing effects on GABAergic transmission, and the functional consequences of
      these ligands are often bidirectional. BZR agonists exert anxiolytic effects,
      whereas the BZR partial inverse agonist FG 7142 has been reported to have
      anxiogenic actions in a variety of paradigms. In keeping with this literature, we
      found that the cardioacceleratory defensive response is enhanced by FG 7142, and
      attenuated by the BZR agonist chlordiazepoxide. In contrast, both compounds
      attenuated basal and fear-potentiated somatic startle responses. This did not
      appear to reflect a global reduction of startle reactivity, however, as the
      cardiac startle response was not significantly altered. These findings support
      the view that multiple substrates underlie distinct aspects or features of fear
      and anxiety. The results are consistent with the suggestion that FG 7142 may
      selectively enhance those aspects of anxiety that depend on cortical-cognitive
      processing.

PMID- 9521550
TI  - Light deprivation produces a therapeutic effect on neglect induced by unilateral
      destruction of the posterior parietal cortex in rats.
AB  - Light deprivation has been found to produce accelerated recovery from severe
      multimodal neglect induced by unilateral destruction of medial agranular cortex,
      the rat analog of area 8 in humans. However, neglect in humans is most often
      produced by destruction of the parietal association cortex. Therefore, the
      present study examined whether light deprivation would produce accelerated
      recovery from severe multimodal neglect induced by unilateral destruction of the
      rodent analog of the parietal association cortex. Subjects received unilateral
      parietal association cortex lesions, and 4 h after surgery were tested for
      neglect of visual, tactile, and auditory stimuli. If severe neglect was obtained,
      subjects experienced either light deprivation, constant light, or a 12:12
      light/dark cycle for 48 h. The results indicated that, relative to the other
      groups, the light deprivation group demonstrated significant accelerated recovery
      from neglect. Recovery was evident on the first post-light deprivation behavioral
      test, and was maintained for the 3 weeks of behavioral testing. The results
      provide further support for the therapeutic effects of light deprivation on
      neglect induced by cortical lesions when light deprivation is administered in the
      immediate postoperative period.

PMID- 9521551
TI  - Impaired spatial working and reference memory in segmental trisomy (Ts65Dn) mice.
AB  - To evaluate the cognitive phenotype of the segmental trisomy 16 (Ts65Dn) mouse, a
      model of Down Syndrome (DS, trisomy 21), we assessed spatial working and
      reference memory using a 12-arm radial maze (RAM). Ts65Dn mice made a greater
      number of reference memory errors across trials compared to control mice. Both
      genotypes showed improvement across trials, although improvement was slower in
      Ts65Dn mice. Ts65Dn mice also made a greater number of working memory errors on
      the RAM, and in contrast to control mice, did not improve across trials, always
      performing at near-chance levels. These results provide evidence for both spatial
      working and reference memory deficits in Ts65Dn mice, characteristics of
      cognitive dysfunction.

PMID- 9521552
TI  - Intermale aggression, GAD activity in the olfactory bulbs and Y chromosome effect
      in seven inbred mouse strains.
AB  - The capacity to attack a passive standard opponent in a resident-intruder test
      and the GAD activity in the olfactory bulbs were measured in 140 male mice from
      seven different inbred mouse strains. The effect of the non-pseudo autosomal
      region of the Y-chromosome (YNPAR) on these two phenotypes has also been
      investigated using a quartet of reciprocal strains congenic for the YNPAR. A
      strong negative correlation was found between the two variables but the YNPAR is
      not involved. This result suggests that males of more attacking strains have a
      lower olfactory threshold, making the olfactory discrimination of the opponent
      easier and its identification as a stranger more efficient.

PMID- 9521553
TI  - Rapid determination of trans-fatty acids in human adipose tissue. Comparison of
      attenuated total reflection infrared spectroscopy and gas chromatography.
AB  - A rapid attenuated total reflection (ATR) infrared (IR) spectroscopy procedure
      was used for quantitating the levels of total trans-fatty acid methyl ester
      (FAME) derivatives in neat (without solvent) test samples isolated from human
      adipose tissue. This procedure requires no weighing of the laboratory sample. The
      single-beam spectrum of the trans-containing FAMEs was 'ratioed' against that of
      a reference material having only cis double bonds in order to obtain a symmetric
      absorption band at 966 cm(-1) on a horizontal background. A single-reflection ATR
      diamond cell that requires only about 1 microl of neat FAMEs was used. The
      average level of trans-fatty acids in human adipose tissue found by ATR (3.07+/
      0.27%) was generally higher than that obtained by gas chromatography (2.59+/
      0.20%). Reasons for such a difference are discussed.

PMID- 9521554
TI  - Improved high-performance liquid chromatographic separation of peptidoglycan
      isolated from various Staphylococcus aureus strains for mass spectrometric
      characterization.
AB  - Reversed-phase high-performance liquid chromatography (RP-HPLC) of muropeptides,
      obtained by muramidase digestion of peptidoglycan in combination with amino acid
      analysis and plasma desorption time-of-flight mass spectrometry is today by far
      the best tool to analyze the fine structure of the peptidoglycans. Here we report
      further improvements of the RP-HPLC separation of muropeptides for analyzing the
      peptidoglycans of various methicillin-resistant strains of Staphylococcus aureus,
      with emphasis on a more detailed characterization of the interpeptide bridge of
      the peptidoglycans of this species.

PMID- 9521555
TI  - Control of hemoglobin synthesis in erythroid differentiating K562 cells. II.
      Studies of iron mobilization in erythroid cells by high-performance liquid
      chromatography-electrochemical detection.
AB  - We have demonstrated that iron controls hemoglobin (Hb) synthesis in erythroid
      differentiating K562 cells by enhancing the activity of a key enzyme of the Hb
      synthesis, delta-aminolevulinate synthase (ALAS). In the present study, we
      studied iron mobilization and the role of iron in erythroid differentiating cells
      by measuring the level of iron by means of high-performance liquid chromatography
      using electrochemical detection (HPLC-ED). After treatment of K562 cells with
      sodium butyrate, the expression of transferrin receptor (TfR) increased
      initially, followed by an increase in the levels of both total iron and Hb as
      well as the ALAS activity. However, no increase could be found in the levels of
      non-heme iron, low-molecular-mass iron (LMMFe) and ferritin. Addition of diferric
      transferrin (FeTf) enhanced both delta-aminolevulinic acid (ALA) and Hb
      synthesis. In contrast, addition of hemin elevated the levels of all iron species
      as well as the Hb synthesis but reduced the TfR expression and ALA contents in
      both butyrate treated and untreated cells. These results suggest that Hb
      synthesis is controlled by TfR expression, and that the ALA synthesis is
      suppressed by iron released from heme and/or Hb due to lowered expression of TfR.

PMID- 9521556
TI  - Simplified method for purification of colostrum to obtain secretory component of
      immunoglobulin A, using secretory component as a reference protein in tracheal
      aspirate fluid.
AB  - Many studies employ bronchoalveolar lavage fluid for assessment of biologically
      active substances secreted from the lung. However, investigators continue to
      search for a useful reference standard to correct for the inevitable but variable
      degree of dilution of this fluid. The glycoprotein, soluble secretory component
      of IgA, may serve as a valid reference protein. We report a simplified method for
      the purification of secretory component from colostrum. Soluble secretory
      component was isolated from human colostrum using serial centrifugation, size
      exclusion fractionation and ion-exchange chromatography. Secretory component rich
      fractions were assayed by enzyme immunoassay. They were also evaluated for total
      amino acid content and distribution and sequence determination with satisfactory
      agreement with published results. We then demonstrated that soluble secretory
      component concentration in tracheal aspirate fluid did not correlate with either
      albumin or with total protein measured in the same samples. Therefore, we
      conclude that the secretory component of IgA serves as a useful reference marker
      because its use may avoid errors resulting from leakage of plasma proteins into
      epithelial lining fluid. Advantages of this method for establishing a standard
      for secretory component include ready availability of soluble secretory
      component, simplicity of the method and relative rapidity of the techniques.

PMID- 9521557
TI  - Study of an anti-human transthyretin immunoadsorbent. Influence of coupling
      chemistry on binding capacity and ligand leakage.
AB  - A variant of transthyretin (TTR Val30Met) has been identified as the main protein
      precursor of the amyloid fibrils deposited in familial amyloidotic polyneuropathy
      (FAP). Specific removal of TTR in an extracorporeal immunoadsorption procedure is
      currently under investigation as a possible treatment of FAP. Immunoadsorbents
      were constructed by immobilizing murine anti-TTR monoclonal antibody 88.6.BA9
      onto agarose gel supports via several different coupling chemistries. The
      influence of coupling conditions such as pH and antibody density, and of
      perfusion variables, such as antigen concentration and applied flow-rate, on the
      TTR capture efficiency, was determined. Cyanogen bromide-, carbonyldiimidazole-
      and aldehyde-activated (ALD) supports conjugated with antibody at optimal pH,
      provided immunoadsorbents with comparable TTR binding capacities. Regarding
      stability, leakage was lowest for the ALD based immunoadsorbents, particularly at
      high pH.

PMID- 9521559
TI  - Separation of proteolytic enzymes originating from Antarctic krill (Euphausia
      superba) by capillary electrophoresis.
AB  - Extracts prepared from Antarctic krill (Euphausia superba), mainly consisting of
      acidic proteolytic enzymes, have been studied with capillary electrophoretic
      techniques. Approximately 50 repeatable peaks were obtained with capillary zone
      electrophoresis on an untreated fused-silica capillary using a phosphate buffer
      containing anionic and cationic fluorosurfactant additives as separation medium.
      A faster separation was achieved on a polyvinyl alcohol coated capillary.
      Quantitative variations of individual proteins regarding different krill enzyme
      batches were noted. In the krill samples trypsin-like serine proteinase,
      carboxypeptidase A and carboxypeptidase B were tentatively identified.

PMID- 9521558
TI  - Analysis of proteins in microsamples of rat airway surface fluid by capillary
      electrophoresis.
AB  - A thin layer of airway surface fluid (ASF) lining the pulmonary airways plays an
      important role in the primary defense mechanisms of the lung against bacterial
      infection. However, little is known about the composition of ASF due to the
      thinness (typically 5-30 microm in healthy animals) of the fluid layer and its
      relative inaccessibility, which causes considerable difficulties in sample
      collection and subsequent analysis. We have used a novel technique of capillary
      sampling coupled with capillary electrophoresis (CE) to analyze the protein
      composition of rat ASF. CE analyses were performed under two different
      conditions: a borate buffer, pH 9.1, or a phosphate buffer, pH 2.5, with 0.5 mM
      spermine. The different selectivities afforded by the two methods aid in peak
      identification, and quantitation of most of the major species was possible using
      both separation conditions. Albumin, transferrin and globulins are observed to be
      the major protein components in rat ASF, at concentrations of 28 mg ml(-1), 4.0
      mg ml(-1) and 34 mg ml(-1) respectively, in comparison to 31 mg ml(-1), 3.1 mg
      ml(-1) and 40 mg ml(-1), respectively, in rat plasma.

PMID- 9521560
TI  - Determination of phosphatidylethanol in blood from alcoholic males using high
      performance liquid chromatography and evaporative light scattering or
      electrospray mass spectrometric detection.
AB  - The 'pathologic' phospholipid, phosphatidylethanol (PEth), formed only in the
      presence of ethanol, was determined in extracts of human blood using high
      performance liquid chromatography with evaporative light scattering detection
      (ELSD) or electrospray (ES) mass spectrometry. Separation was performed using a
      diol column and a normal-phase binary gradient system. Decreasing concentrations
      of PEth (15 to 1 nmol/ml blood) could be detected by ELSD in three male
      alcoholics, up to 3 weeks after the beginning of an alcohol-free period. Using
      ES, levels down to 100 pmol/ml blood was detected. The molecular species of PEth
      were similar to those of phosphatidylcholine found in the same blood sample. The
      method provides a rapid quantitative and qualitative determination of PEth in
      blood. The limits of detection were 200 pmol (approximately 125 ng) using ELSD
      and 140 fmol (approximately 100 pg) using ES, total amounts injected. ON

PMID- 9521561
TI  - Comparison of anion-exchange and ion-modified reversed-phase liquid
      chromatography for the determination of S-sulfocysteine.
AB  - A dual Hg-Au amalgam electrode is used to detect S-sulfocysteine (SSC) in this
      study. There exist two main components in the acetonitrile (ACN) rat brain
      extracts, namely, Cl- and GSSG (oxidized glutathione), that are active in our
      detection system (GSH is not extracted in ACN). Two strong anion-exchange columns
      from different companies were used to separate the samples under different
      conditions, but SSC and Cl- were not separated at the optimum detection pH of
      5.2. The signal from Cl- was greatly decreased by lowering the potential at the
      downstream electrode, though it cannot be completely eliminated. While a silver
      cartridge removed Cl- from micromoles to several millimoles without any negative
      effect on the SSC signal in aqueous standards, a large negative peak which
      interferes with SSC detection was unfortunately introduced when a silver
      cartridge was applied to brain tissue samples. However, SSC and Cl- in the
      samples are successfully separated by ion-modified reversed-phase LC in acetate
      buffer at the optimum detection pH (5.2). The separation conditions are 20 mM
      acetic acid, 2% methanol, 0.5 mM cetyltrimethylammonium p-toluene sulfonate
      (CTMA) (pH 5.2). Most importantly, the sensitivity of SSC under the optimum
      separation conditions is not sacrificed. The detection limit is 8 nM (20 microl
      injected).

PMID- 9521562
TI  - Use of an immunoaffinity column for tetrachlorodibenzo-p-dioxin serum sample
      cleanup.
AB  - Covalently linking 1-amino-3,7,8-trichlorodibenzo-p-dioxin with either keyhole
      limpet hemocyanin (KLH) or bovine serum albumin (BSA) provided antigens that
      generated antibodies in chickens. Competitive ELISA analysis demonstrated that
      the antibodies isolated from egg yolk (IgY) bound with 1,3,7,8-tetrachlorodibenzo
      p-dioxin (1,3,7,8-TCDD). The antibodies were linked to CNBr-Sepharose to generate
      an immunoaffinity column. Radiolabeled 1,3,7,8-TCDD in a 0.05% Tween 20 solution
      was retained by the column and could be eluted by increasing the Tween 20
      concentration. The binding efficiency for 10.7 ng per ml gel matrix ranged from
      85 to 97%. Immunoaffinity columns generated by this method did not effectively
      bind 14C-1,3,7,8-TCDD from serum samples. Diluting the serum 1:20 with 0.05%
      Tween 20 increased the binding efficiency. Alternately, ethanol-hexane extraction
      followed by solid phase extraction on a carbon column using a fat removal
      protocol also provided an appropriate preaffinity column cleanup for serum
      samples. After this preaffinity column cleanup, spiked serum samples applied to
      the immunoaffinity column showed binding efficiencies of over 90%.

PMID- 9521563
TI  - Single step thin-layer chromatographic method for quantitation of enzymatic
      formation of fatty acid anilides.
AB  - The activity of the enzyme involved in catalyzing the formation of fatty acid
      anilides can be measured by quantitating the fatty acid anilides formed. We have
      shown earlier that oleic acid is the most preferred substrate among other fatty
      acids studied for the conjugation with aniline. The reaction product (oleyl
      anilide) could be separated by thin-layer chromatography (TLC) and then
      quantified by reversed-phase high-performance liquid chromatography (HPLC). Using
      [1-(14)C]oleic acid as substrate, the fatty acid anilide forming activity can be
      determined in a single step by TLC analysis. The conventional TLC methods used
      for the separation of the fatty acid esters, however, could not resolve oleyl
      anilide from the residual [1-(14)C]oleic acid. Therefore, a simple and reliable
      TLC method was developed for the separation of oleyl anilide from oleic acid
      using a freshly prepared solvent consisting of petroleum ether-ethyl acetate
      ammonium hydroxide (80:20:1, v/v). Using this solvent system the relative flow
      (Rf) values were found to be 0.54 for oleyl anilide and 0.34 for aniline, whereas
      oleic acid remained at the origin. The TLC procedure developed in the present
      study could be used to determine the fatty acid anilide forming activity using [1
      (14)C]oleic or other fatty acids as substrate and was also found suitable for the
      analysis of fatty acid anilides from the biological samples.

PMID- 9521565
TI  - Gas chromatographic-mass spectrometric determination of serum mexiletine
      concentration after derivatization with perfluorooctanoyl chloride, a new
      derivative.
AB  - Mexiletine is an antiarrhythmic agent used in the treatment of ventricular
      arrhythmia. The drug has a narrow therapeutic window which necessitates
      monitoring its serum concentrations. We describe a gas chromatographic-mass
      spectrometric analysis of mexiletine using selected ion monitoring. Mexiletine
      was extracted from alkaline serum with dichloromethane and then derivatized with
      perfluorooctanoyl chloride. The derivatization reaction was completed in 20 min
      at 80 degrees C. We used N-propylamphetamine as the internal standard. The ions
      monitored were m/z 122, 454 and 575 for the derivatized mexiletine and m/z 91,
      118, 440 and 452 for the derivatized internal standard. The within-run precision
      at a serum mexiletine concentration of 1 mg/l was 1.9% (mean=0.98, S.D.=0.019
      mg/l, n=7) and the between-run precision was 2.5% (mean=0.99, S.D.=0.025 mg/l,
      n=7). The assay was linear for serum mexiletine concentrations of 0.2 to 4 mg/l.
      The detection limit was 0.1 mg/l. The average recoveries of mexiletine and the
      internal standard were 80% and 84%, respectively at a mexiletine concentration of
      1 mg/l. There was no carry over problem in our assay. We observed a good
      correlation between mexiletine concentrations measured by a reference laboratory
      (GC) and by our new GC-MS assay.

PMID- 9521564
TI  - Immunological analysis of methamphetamine antibody and its use for the detection
      of methamphetamine by capillary electrophoresis with laser-induced fluorescence.
AB  - An accurate, simple and rapid immunoassay is demonstrated for the detection of
      methamphetamine in urine by capillary electrophoresis (CE) with laser-induced
      fluorescence (LIF). An aminobutyl derivative of methamphetamine was conjugated
      with proteins, and used as an immunogen to produce antibodies for the assay. The
      methamphetamine derivative was also labeled with fluorescein isothiocyanate
      (FITC) to compete with free methamphetamine in the sample for the antibody
      binding site. Levels of free and antibody-bound FITC-labeled methamphetamine were
      monitored by performing CE-LIF using an untreated fused-silica column. This
      competitive immunoassay used antiserum instead of purified antibody or antibody
      fragment, yet was found to have good precision with a sensitivity of lower than
      20 ng/ml. Various antibodies were also screened, and cross-reactivity of anti-MA
      antibody with methamphetamine analogues were also investigated. The results
      indicate that CE-LIF-based immunoassay is a powerful tool for the screening and
      characterization of antibody and may have possible applications in the detection
      of abused drugs in urine.

PMID- 9521566
TI  - Microscale high-performance liquid chromatography-electrospray tandem mass
      spectrometry assay for cyclosporin A in blood.
AB  - To facilitate quantitative analysis of cyclosporin A in low volume blood samples
      we developed a sensitive and specific microscale reversed-phase HPLC-electrospray
      tandem mass spectrometry assay. Blood samples (100 microl) were prepared by
      acetonitrile precipitation and C18 solid-phase extraction. Detection was by
      multiple-reactant monitoring. The method was linear over the range 5-1000
      microg/l (r> or =0.997) with accuracy between 95.4 and 102.0% over this range.
      Total imprecision was 11.1% at 10 microg/l and 2.8% at 800 microg/l. Absolute
      recovery of cyclosporin A and internal standard was 72.5 and 73.3%, respectively.
      When this method was evaluated against a conventional HPLC with UV detection, in
      patient samples, they were interchangeable (y=0.988x + 10.0, r=0.996). This HPLC
      ESI-MS-MS method will be applicable to therapeutic monitoring in paediatric
      transplant patients and multiple point pharmacokinetic studies in animals and
      humans.

PMID- 9521567
TI  - Tissue extraction and high-performance liquid chromatographic determination of
      ketoprofen entantiomers.
AB  - Local transcutaneous delivery of non-steroidal anti-inflammatory drugs avoids
      gastrointestinal side effects and concentrates drugs in the intended tissues. An
      extraction and HPLC method was developed for ketoprofen in skin, fascia and
      muscle. Tissue samples were homogenized in NaHCO3. After methylene chloride
      removal of lipids, the aqueous layer was acidified with HCl and back extracted
      into isooctane/isopropanol. Ketoprofen was derivatized with ethylchloroformate/S
      (-)-alpha-phenylethylamine in triethylamine, then detected by HPLC. Ketoprofen
      recovery was linear (1-33 microg/g) and was detected in these tissues following
      in vivo cathodic iontophoresis (160 mA*min). This represents the first non
      radioactive method for determination of ketoprofen in tissues following
      transcutaneous iontophoresis.

PMID- 9521568
TI  - Simultaneous measurement of venlafaxine and its major metabolite,
      oxydesmethylvenlafaxine, in human plasma by high-performance liquid
      chromatography with coulometric detection and utilisation of solid-phase
      extraction.
AB  - Venlafaxine, oxydesmethylvenlafaxine and an internal standard (paroxetine) were
      extracted from plasma by a solid-phase extraction technique. Chromatography was
      performed using isocratic reversed-phase high-performance liquid chromatography
      (HPLC) with coulometric endpoint detection. The standard curves were linear over
      the range 0-200 ng/ml for both venlafaxine and oxydesmethylvenlafaxine in plasma.
      The mean inter- and intra-assay coefficients of variation over the range of the
      standard curves were less than 10%. The absolute recovery averaged 74% for
      venlafaxine and 67% for oxydesmethylvenlafaxine. The sensitivity was 0.5 ng for
      both the analytes. Plasma profiles of the analytes following oral administration
      of venlafaxine, are presented.

PMID- 9521569
TI  - Determination of acetylsalicylic acid and salicylic acid in skin and plasma by
      high-performance liquid chromatography.
AB  - This study describes a HPLC method to determine the concentrations of
      acetylsalicylic acid (ASA) and salicylic acid (SA) in human stratum corneum and
      in plasma. The stratum corneum layers for ASA/SA analysis were removed from three
      patients with postherpetic hyperalgesia treated with topical and oral aspirin.
      Blood samples were also collected from the same patients. Tape strippings were
      placed in acetonitrile and sonicated for 15 min. After centrifuging, aliquots of
      the supernatant were injected into the chromatograph. ASA and SA from plasma
      samples were extracted on Isolute C8 columns. Due to interfering peaks in the
      tape samples, HPLC conditions were slightly different for tape and plasma
      samples. ASA and SA were separated on a LiChrospher 100 RP-18 column at 1 ml/min
      using a water-phosphate buffer (pH 2.5)-acetonitrile mobile phase (35:40:25,
      v/v/v). A linear response to quantities of ASA from 0.1 to 100 microg/cm2 and of
      SA from 0.1 to 5 microg/cm2 in tape and to quantities of ASA 0.1 to 2 microg/ml
      and 1 to 50 microg/ml was obtained and the recovery from tape and plasma samples
      was over 98%. The method is sensitive (0.1 microg/cm2) and specific enough to
      allow the determination of the drugs in the skin not only after topical but also
      after oral administration. A good sensitivity was also obtained in plasma (0.1
      microg/ml) allowing study of the kinetics of ASA and SA in plasma after oral
      administration. Concentrations of ASA after topical administration were 100-200
      times higher than after oral administration. Plasma levels of ASA and SA after
      oral administration were similar to those previously found. No ASA or SA were
      detected in plasma after topical ASA administration.

PMID- 9521570
TI  - High-performance liquid chromatographic-electrochemical assay for the
      quantitation of BMS-181885 in monkey plasma.
AB  - A high-performance liquid chromatographic-electrochemical assay was developed and
      validated for the quantitation of BMS-181885 (I), an anti-migraine agent, in
      monkey plasma. The assay involved a solid-phase extraction of I and BMY-46317
      (internal standard; I.S.) on a 1-ml cyano cartridge using the automatic solid
      phase extraction cartridge (ASPEC) system. Immediately following the conditioning
      of the cyano column (3 ml of methanol and 2 ml of 1% glacial acetic acid), plasma
      (0.25 ml) was loaded on to the column. The column was then washed with a 3 ml of
      0.1 M ammonium acetate buffer (pH 6). The final elution of the analytes was
      performed using 2 ml of methanol. The eluate was then evaporated to dryness
      (gentle stream of nitrogen at 40 degrees C) and the residue was dissolved in the
      mobile phase and injected on to a YMC basic column (15 cm x 4.6 mm; 5 microm
      particle size) at a flow-rate of 1 ml/min. A mixture of 0.1 M ammonium acetate at
      pH 6-acetonitrile-methanol (70:20:10, v/v) was used as the mobile phase. Standard
      curves, with a lower limit of quantitation of 2 ng/ml of I were linear (r2> or
      =0.998; range: 2-50 ng/ml). Based on the analysis of the quality control (QC)
      samples, the assay was both accurate and precise. The stability of I was
      established following freeze-thaw cycles and storage at or below -20 degrees C.
      The extraction recovery of I from monkey plasma was about 82%. The validated
      assay method was applied to determine the pharmacokinetics of I in monkeys
      following a single 1 mg/kg intravenous dose.

PMID- 9521571
TI  - Sensitive liquid chromatographic technique to measure isoniazid in alveolar
      cells, bronchoalveolar lavage and plasma in HIV-infected patients.
AB  - The need to monitor the effectiveness of antimicrobial drugs in treating
      opportunistic infections such as tuberculosis in HIV-infected patients requires
      the development of sensitive assays. A suitable HPLC method was developed to
      measure the concentration of isoniazid (INH) in plasma 1 h after a standard 300
      mg dose and to detect the low levels typically found in alveolar cells obtained
      by bronchoalveolar lavage of subjects maintained on a standard regimen of the
      drug. Following extraction with a chloroform-butanol mixture, the INH was back
      extracted into dilute acid which was subsequently analyzed by HPLC using a CN
      reversed-phase column and an acetonitrile-isopropanol based mobile phase. Another
      HPLC method was developed using direct injection and a polymer based column to
      measure minute concentrations of INH in the cell-free lavage. In both systems,
      detection of the drug was accomplished with a sealed coulometric detector (+0.6
      V) capable of giving a consistent daily response without adjustment. When saline,
      cellular extracts and plasma from untreated subjects were spiked with various
      amounts of INH and analyzed, the lowest level of quantitation was 10, 25 and 100
      ng/ml, respectively. Calibration curves showed good linearity when spiked
      concentrations were compared to peak areas (r=0.991, 0.993 and 0.998,
      respectively). Alveolar cell extracts and cell-free bronchoalveolar fluid from
      HIV-positive patients maintained on a standard INH regimen had detectable levels
      of INH 4 h after a 300 mg oral dose. The plasma INH at 1 h had a range of 0.3-7.1
      microg/ml (n = 50). Precision studies with plasma spiked at 0.1, 0.5, 1.0 and 5.0
      microg/ml revealed within-run coefficients of variation (C.V.s) of 8.9, 7.2, 4.2
      and 4.9%, respectively and analytical recoveries of 97, 108, 108 and 98%,
      respectively. The day-to-day C.V.s for the plasma method were 7.6, 4.9 and 3.8%
      at concentrations of 0.5, 1.0 and 3.0 microg/ml, respectively. The results
      suggest that this rugged HPLC technique can quantitate INH in 1 h plasma with
      good precision and can be used to estimate the very low INH concentrations found
      in alveolar cells and cell-free lavage recovered from patients undergoing anti
      tuberculosis therapy.

PMID- 9521572
TI  - Semi-automatic liquid chromatographic analysis of pamidronate in serum and
      citrate plasma after derivatization with 1-naphthylisothiocyanate.
AB  - The semi-automatic method for the determination of the bisphosphonate pamidronate
      in serum and citrate plasma involves a manual protein precipitation with
      trichloroacetic acid and a manual coprecipitation of the bisphosphonate with
      calcium phosphate, followed by an automated solid-phase extraction on anion
      exchange columns. After off-line evaporation of the extract under nitrogen and
      reconstitution in water, the automatic procedure is continued by automatic
      derivatization with 1-naphthylisothiocyanate, ion-pair liquid-liquid extraction
      and a treatment with hydrogen peroxide, prior to analysis by ion-pair HPLC and
      fluorescence detection at 285/390 nm. The intra- and inter-day precisions are 1.3
      and 7%, respectively, for a standard of 100 ng ml(-1) pamidronate in serum; the
      average accuracy for this standard is 107%. The lower limit of quantification is
      20 ng ml(-1) pamidronate in 1 ml of human serum.

PMID- 9521573
TI  - Application of capillary electrophoresis to the separation of structurally
      diverse N-(substituted)-glycine-peptoid combinatorial mixtures.
AB  - The capillary electrophoresis (CE)-based separation of five N-(substituted)
      glycine (NSG)-peptoid mixtures with a wide range of physical and chemical
      properties was studied. A CE separation, initially developed using a single
      representative peptoid mixture, with a background electrolyte (BGE) modified by
      the addition of both methyl-beta-cyclodextrin and heptane sulfonic acid was found
      to provide good separations of most of the combinatorial mixtures investigated.
      For those mixtures not separated well by this procedure, the use of SDS micelles
      in conjunction with methyl-beta-cyclodextrin resulted in dramatic improvements in
      the separation. While no single set of separation conditions proved sufficient
      for all of the NSG-peptoid combinatorial mixtures, the two methods were able to
      provide separation sufficient for characterization of a set of mixtures with a
      wide range of physical and chemical properties. The efficiency of the CE-based
      separation of the combinatorial mixtures studied was compared to a reversed-phase
      liquid chromatographic method using gradient elution.

PMID- 9521574
TI  - Resolution of fibronectin and other uncharacterized proteins by two-dimensional
      polyacrylamide electrophoresis with thiourea.
AB  - Several proteins, which are recognized components of serum, are not resolved by
      two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) under standard
      conditions. One major example is fibronectin, which is detected in fairly high
      concentration (milligram range) by immunoassays, while undetectable in 2D-PAGE
      gels. Following several experiments with a combination of zwitterionic and
      chaotropic substances we obtained a good resolution of the protein in gels
      containing 0.5 M thiourea plus 8 M urea. By this technique, fibronectin was, for
      the first time, found to be microheterogeneous between pl values of 5.3 and 5.6.
      Besides fibronectin we detected three other families of uncharacterized proteins
      with Mr of 130000, 110000 and 34000 respectively, whose identity and function are
      currently under investigation.

PMID- 9521575
TI  - Nicotine monitoring in sweat with a sweat patch.
AB  - In recent years, remarkable advances in sensitive analytical techniques have
      enabled the analysis of drugs in unconventional samples, such as sweat. In a
      study conducted with cigarettes smokers and nonsmokers, PharmChek sweat patches
      were applied to 29 subjects for 72 h. Nicotine was extracted in 5 ml methanol in
      the presence of 200 ng nicotine-d4, used as internal standard. After 20 min
      agitation, the methanolic solution was evaporated to dryness in the presence of
      10 microl octanol to ensure nonvolatility of nicotine. Nicotine was determined
      using gas chromatography coupled to mass spectrometry after separation on a 30-m
      capillary HP5 MS column. The assay was linear in the range 50-2500 ng/patch, with
      an extraction recovery of 76+/-5%. Limit of detection was 10 ng/patch. Nicotine
      concentrations in sweat were not detected for the nonexposed nonsmokers (n = 8),
      87 to 266 ng/patch for the passive smokers (n = 6) and 150 to 2498 ng/patch for
      the smokers (n = 15). This study demonstrated a useful application of the sweat
      patch for monitoring tobacco exposure.

PMID- 9521576
TI  - Use of high-performance liquid chromatography for the estimation of
      polychlorinated biphenyls and p,p-DDE residues in marine mammals.
AB  - We present a screening technique for the detection of polychlorinated biphenyls
      (PCBs) and p,p-DDE residue levels in marine mammal blubber using high-performance
      liquid chromatography (HPLC). This method modifies the standard extraction and
      clean-up methods for organochlorines for use with HPLC and uses a method of
      chemical derivatization to separate and semi-quantify the two organochlorines
      with HPLC.

PMID- 9521577
TI  - In vitro and in vivo metabolism of myristicin in the rat.
AB  - Myristicin [5-allyl-1-methoxy-2,3-(methylenedioxy)benzene] is a flavoring plant
      constituent and has been known to produce significant psychopharmacological
      responses as well as insecticidal activity. From in vitro and in vivo metabolism
      of myristicin, the two metabolites 5-allyl-1-methoxy-2,3-dihydroxybenzene and 1'
      hydroxymyristicin were identified using GC-MS after derivatization of sample
      matrices with a mixture of BSTFA-TMCS. Those metabolites from in vitro study were
      also confirmed in urine after an oral administration of myrisitcin to rats, and
      enzymatic hydrolysis of urine suggested that these metabolites were excreted as
      conjugated forms as well.

PMID- 9521578
TI  - Increased rate of nondisjunction in sex cells derived from low-quality semen.
AB  - The relationship between chromosomal nondisjunction and semen quality was studied
      in two groups of males who differ highly in their semen quality: 12 individuals
      with low-quality semen caused by varicocele, and 8 subjects with high-quality
      semen, selected from sperm donors for in vitro fertilization. Chromosomal
      nondisjunction was inferred from the rate of disomy found in mature sperm cells.
      To determine the rate of disomy, we applied fluorescence in situ hybridization
      using satellite-specific probes for chromosomes 1, 15, 18, X and Y. In sperm
      cells of males with low-quality semen, the mean rate of disomy for each of the
      autosomes and of hetero-disomy for the sex chromosomes (XY) was significantly
      higher than that observed in the high-quality semen samples: more than 15-fold
      higher for chromosomes 1 and 15, and 7-fold higher for chromosomes 18 and XY.
      Yet, the homo-disomy rate for each of the sex chromosomes (XX and YY) was almost
      the same in both types of semen. The large discrepancy between the low- and high
      quality semen in the rate of sex chromosome hetero-disomy versus the similar rate
      of homo-disomy strongly suggests that the abnormal chromosomal segregation in
      meiocytes of males with low-quality semen resulted from chromosomal
      nondisjunction at the first meiotic division. The results indicate that men
      showing poor semen quality are at an increased risk for meiotic nondisjunction,
      similar to women at the end of their reproductive years.

PMID- 9521579
TI  - Inheritance of chronic tension-type headache investigated by complex segregation
      analysis.
AB  - We investigated the mode of inheritance of chronic tension-type headache in 122
      families. The probands were from the Copenhagen Headache Clinic, Denmark. The
      criteria of the International Headache Society were used. The patterns of
      segregation of chronic tension-type headache were assessed by complex segregation
      analysis performed with the computer program POINTER. Of the 122 probands with
      chronic tension-type headache, 56 had 71 first-degree relatives with chronic
      tension-type headache. The complex segregation analysis indicates that chronic
      tension-type headache has multifactorial inheritance.

PMID- 9521580
TI  - DNA polymorphisms and haplotypes in the human transferrin gene.
AB  - Although a large number of human serum transferrin (TF) variants have been
      described, only one RFLP (AvaI) has so far been found. Here we report three new
      RFLPs (MvaI in intron 5 and exon 7, BbvI in exon 7) and correlations between
      RFLPs and between RFLPs and serum TF types. There were strong, but not always
      complete, disequilibria between RFLP and serum protein alleles. Thus, the most
      common serum TF variant, C1, was heterogeneous and could be subdivided into two
      common haplotypes, whereas the C2, C3, and DCHI variants were completely or
      almost completely (C2) homogeneous. There was a total genotypic agreement between
      the BbvI polymorphism and the presence/absence of the TF C3 variant, and the
      mutation that creates the BhvI site was found to lead to a G258S amino acid
      substitution.

PMID- 9521581
TI  - The mutations in FGFR2-associated craniosynostoses are clustered in five
      structural elements of immunoglobulin-like domain III of the receptor.
AB  - Exons 5 and 7 of the fibroblast growth factor receptor 2 (FGFR2) gene code for
      immunoglobulin-like domain III (IgIII) and for the region connecting the second
      and the third Ig domain of the receptor. Numerous mutations in these two exons
      have been shown to cause various craniosynostotic syndromes. Here, we describe
      three previously unrecognized mutations at amino acid positions 276, 301, and
      314, in one nonspecific craniosynostosis and in two Crouzon patients. We also
      present a polypeptide model of IgIII of FGFR2. The known mutations involve five
      distinct structural elements of the receptor. The changes within these elements
      affect receptor function by various mechanisms, including altered dimerization,
      truncation, increased mobility between Ig domains, disintegration of IgIII, and
      alteration of the ligand-binding site.

PMID- 9521582
TI  - Failure of testicular development associated with a rearrangement of 9p24.1
      proximal to the SNF2 gene.
AB  - In 46,XY individuals, testes are determined by the activity of the SRY gene (sex
      determining region Y), located on the short arm of the Y chromosome. The other
      genetic components of the cascade that leads to testis formation are unknown and
      may be located on the X chromosome or on the autosomes. Evidence for the
      existence of several loci associated with failure of male sexual development is
      indicated by reports of 46,XY gonadal dysgenesis associated with structural
      abnormalities of the X chromosome or of autosomes (chromosomes 9, 10, 11 and 17).
      In this report, we describe the investigation of a child presenting with multiple
      congenital abnormalities, mental retardation and partial testicular failure. The
      patient had a homogeneous de novo 46,XY,inv dup(9)(pter-->p24.1::p21.1-
      >p23.3::p24.1-->qter) chromosome complement. No deletion was found by either
      cytogenetic or molecular analysis. The SRY gene and DSS region showed no
      abnormalities. Southern blotting dosage analysis with 9p probes and fluorescent
      in situ hybridisation data indicated that the distal breakpoint of the duplicated
      fragment was located at 9p24.1, proximal to the SNF2 gene. We therefore suggest
      that a gene involved in normal testicular development and/or maintenance is
      present at this position on chromosome 9.

PMID- 9521583
TI  - Detection of structural abnormalities in spermatozoa of a translocation carrier
      t(3;11)(q27.3;q24.3) by triple FISH.
AB  - Structural chromosome abnormalities in spermatozoa represent an important
      category of paternally transmittable genetic damage. A couple was referred to our
      centre because of repetitive abortions and the man was found to be a carrier of a
      reciprocal translocation t(3;11)(q27.3;q24.3). A tailored fluorescence in situ
      hybridisation (FISH) approach was developed to study the meiotic segregation
      patterns in spermatozoa from this translocation carrier. A combination of three
      DNA probes was used, a centromeric probe for chromosome 11, a cosmid probe for
      chromosome 11q and a YAC probe for chromosome 3q. The frequency of spermatozoa
      carrying an abnormal chromosome constitution was compared with baseline
      frequencies in control semen specimens and it was found that a significantly
      higher percentage of spermatozoa carried an abnormal constitution for the
      chromosomes involved in the translocation. A normal or balanced chromosome
      constitution was found in 44.3% of the analysed spermatozoa, while the remainder
      exhibited an abnormal chromosome constitution reflecting different modes of
      segregation (15.9% adjacent I segregation, 6.5% adjacent II segregation, 28.9%
      3:1 segregation, 0.8% 4:0 segregation, 3.6% aberrant segregation). The frequency
      of aneuploidy for chromosomes X, Y, 13 and 21 was assessed using specific probes
      but there was no evidence of interchromosomal effects or variations in the sex
      ratio in spermatozoa from the translocation carrier. In conclusion, structural
      aberrations can be reliably assessed in interphase spermatozoa using unique DNA
      probe cocktails, and this method provides insight into the genetic constitution
      of germ cells and enables evaluation of potential risks for the offspring.

PMID- 9521584
TI  - Retroviral gene transfer for the assignment of Fanconi anemia (FA) patients to a
      FA complementation group.
AB  - Fanconi anemia (FA) is an autosomal recessive disorder characterized by bone
      marrow failure, cancer susceptibility, and a variety of developmental defects.
      The disease is clinically heterogeneous; eight different complementation groups
      (FA A-H) and, thus, genetic loci have been discovered. Two genes, FAA and FAC,
      have been cloned. Disease-associated mutations have been detected and rapid
      mutation screening makes possible the assignment of patients without resorting to
      time-consuming cell fusion and complementation analysis. Amplification of
      specific cDNAs from RNA followed by direct or indirect sequence analysis is a
      standard method for mutation detection. During the course of such examinations of
      the FAC gene, we have noted that frequently only one of the expressed alleles is
      successfully amplified. This can lead to false assignment of patients to a
      complementation group. As we report here, such cases can be rapidly clarified by
      retroviral gene transfer and complementation analysis.

PMID- 9521585
TI  - Refined localisation of the voltage-gated chloride channel, CLCN3, to 4q33.
AB  - Mutations in ion channels have been shown to be responsible for a variety of
      neurological and muscular diseases. The voltage-gated chloride channel CLCN3 was
      recently mapped to chromosomal region 4q32. We are analysing a young female
      patient with Wolf-Hirschhorn syndrome and chorea associated with an inversion
      deletion of chromosome 4 [46XX,inv(4)del(4)(qter-->q33::p15.32-->q33].
      Considering that chorea in this patient might be due to the disruption of a gene
      at either of the 4p15.32 or 4q33 breakpoints, CLCN3 was considered as a candidate
      gene. We showed by FISH analysis with a CLCN3 YAC that the gene was not broken by
      the inv-del event, and was therefore an unlikely candidate. Using high resolution
      techniques, we refined the localisation of CLCN3 to 4q33.

PMID- 9521586
TI  - Transmission of mitochondrial DNA heteroplasmy in normal pedigrees.
AB  - The presence of multiple mitochondrial genotypes (heteroplasmy) has been studied
      in normal individuals. Six multigenerational normal families were screened for
      heteroplasmy by PCR of the mitochondrial control region and the cytochrome c
      oxidase intergenic regions. Two individuals from different families exhibited
      multiple length polymorphisms in a homopolymeric tract at positions 16184-16193
      and a grandmother in a third family was heteroplasmic for both cytosine and
      thymidine at position 15945. Although the 15945 T variant comprised 28% of the
      grandmother's mitochondrial DNA, this sequence was not present in any of her
      descendants. Heteroplasmy was detected in 2.5% of the 96 mother-offspring pairs,
      consistent with the possibility that it may not be rare.

PMID- 9521587
TI  - A double missense mutation in the ATM gene of a Dutch family with ataxia
      telangiectasia.
AB  - Ataxia telangiectasia (AT) is an autosomal recessive disorder characterized by
      cerebellar ataxia, telangiectasia, immunodeficiency, elevated alpha-fetoprotein
      levels, chromosomal instability, predisposition to cancer, and radiation
      sensitivity. We report the identification of a new, double missense mutation in
      the ataxia telangiectasia gene (ATM) of a Dutch family. This homozygous mutation
      consists of two consecutive base substitutions in exon 55: a T-->G transversion
      at position 7875 of the ATM cDNA and a G-->C transversion at position 7876. These
      transversions were confirmed by polymerase chain reaction/primer-induced
      restriction analysis with CelII. The double base substitution results in an amino
      acid change of an aspartic acid to a glutamic acid at codon 2625 and of an
      alanine to a proline at codon 2626 of the ATM protein. Both amino acids are
      conserved between the ATM protein and its functional homolog, the Atm gene
      product in the mouse. Furthermore, the Chou-Fasman and Robson predictions both
      demonstrate a change in the secondary structure of the ATM protein carrying the
      D2625E/A2626P mutation. These findings suggest that the double base substitution
      in the ATM gene is a disease-causing mutation.

PMID- 9521588
TI  - Structure of the human amyloid-precursor-like protein gene APLP1 at 19q13.1.
AB  - Amyloid-precursor-like protein 1 (APLP1) is a membrane-associated glycoprotein,
      whose gene is homologous to the APP gene, which has been shown to be involved in
      the pathogenesis of Alzheimer's disease. APLP1 is predominantly expressed in
      brain, particularly in the cerebral cortex postsynaptic density. The genomic
      organization of mouse APLP1 has been determined, and the human gene has been
      mapped to chromosomal region 19q13.1. In the present study, the entire sequence
      of human APLP1 has been determined from a cosmid clone, and the genomic structure
      has been determined. The gene is 11.8 kb long and contains 17 exons. We have
      previously mapped the gene for congenital nephrotic syndrome (CNF) to the APLP1
      region, to the vicinity of marker D19S610 located between markers D19S191 and
      DS19608. APLP1 is the only known gene in the vicinity of the marker D19S610.
      Because of its location and the proposed interference of amyloid with basement
      membrane assembly, APLP1 has been considered a candidate gene for CNF. All exon
      regions of the gene were amplified by the polymerase chain reaction and sequenced
      from DNA of CNF patients. No differences were observed between CNF patients and
      controls, suggesting that mutations in APLP1 are not involved in the etiology of
      CNF.

PMID- 9521590
TI  - Localization of the gene responsible for Peutz-Jeghers syndrome within a 6-cM
      region of chromosome 19p13.3.
AB  - Patients with Peutz-Jeghers syndrome (PJS), an autosomal dominant disease
      characterized by hamartomatous polyposis of the gastrointestinal tract, are
      thought to be predisposed to malignancies of the digestive tract, genital tract,
      and other organs. Using microsatellite markers on chromosome 19p, we have closely
      defined the region containing the gene responsible for this disorder through
      linkage analysis in seven affected families. The lack of obligate recombinants at
      two of these loci, D19S883 and D19S878, with maximum LOD scores of 2.88 and 3.75,
      confirmed the localization of the PJS locus to chromosome 19. Furthermore,
      haplotype analysis placed the PJS locus within a 6-cM telomeric region of
      chromosome 19p, between D19S886 and D19S565.

PMID- 9521591
TI  - Quantitative DNA pooling to increase the efficiency of linkage analysis in
      autosomal dominant disease.
AB  - DNA pooling is an efficient method to rapidly perform genome-wide linkage scans
      in autosomal recessive diseases in inbred populations where affected individuals
      are likely to be homozygous for alleles near the disease gene locus. We wanted to
      examine whether this approach would detect linkage in autosomal dominant (AD)
      disorders where affected individuals may share one allele identical by descent at
      loci tightly linked to the disease. Two large outbred pedigrees in which the AD
      diseases familial venous malformation (FVM) and hereditary hemorrhagic
      telangiectasia (HHT1), linked to 9p and 9q, respectively, were investigated.
      Separate pools of DNA from affected (n = 21 for FVM and 17 for HHT1) and
      unaffected family members (n = 9 FVM and HHT1), and 25 unrelated population
      controls were established. Polymorphic markers spanning chromosome 9 at
      approximately 13.5-cM intervals were amplified using standard PCR. Allele
      quantitation was performed with a fluorimager. Visual inspection of allele
      intensities and frequency distributions suggested a shift in frequency of the
      most common allele in the affecteds lane when compared to control lanes for
      markers within 30 cM of the FVM and HHT1 loci. These subjective assessments were
      confirmed statistically by testing for the difference between two proportions
      (one-sided; P < or = 0.05). When using population controls, the true-positive
      rates for FVM and HHT1 were 5/5 and 2/5 markers, respectively. False-positive
      rates for FVM and HHT1 were 3/9 and 2/9, respectively. In both AD diseases
      investigated, quantitative DNA pooling detected shifts in allele frequency, thus
      identifying areas of known linkage in most cases. The utility of this technique
      depends on the size of the pedigree, frequency of the disease-associated allele
      in the population, and the choice of appropriate controls. Although the false
      positive rate appears to be high, this approach still serves to reduce the amount
      of overall genotyping by about 60%. DNA pooling merits further investigation as a
      potential strategy in increasing the efficiency of genomic linkage scans.

PMID- 9521589
TI  - A germline mutation abolishing the original stop codon of the human adenine
      phosphoribosyltransferase (APRT) gene leads to complete loss of the enzyme
      protein.
AB  - Adenine phosphoribosyltransferase (APRT) is a purine metabolic enzyme and a
      homozygous deficiency in this enzyme causes 2,8-dihydroxyadenine urolithiasis.
      Various germline abnormalities have been described, but we report here a unique
      type of germline mutation in a homozygous individual (SY) who had excreted 2,8
      dihydroxyadenine crystals. In SY, TCA was substituted for the physiological stop
      codon TGA. This base substitution generates a new HinfI restriction site, and,
      using the polymerase chain reaction and subsequent digestion by this enzyme, it
      was confirmed that SY is homozygous for the base substitution. This base change
      is unique in that it generates an open reading frame that extends to the poly(A)
      addition site. The amount of mRNA in transformed B cells from SY was
      approximately a quarter of that in control subjects and no APRT proteins were
      detected. In eukaryotes, unlike in prokaryotes, no rescue systems for defective
      polypeptide termination caused by a missing stop codon have been found.
      Therefore, the outcome of the defect of SY is unclear from present knowledge
      about termination of polypeptide synthesis. Investigations into the mechanisms of
      the absence of protein in the cells of SY may lead to a better understanding of
      the physiological and nonphysiological termination of polypeptide synthesis in
      eukaryotic cells.

PMID- 9521592
TI  - A novel missense mutation (S18N) in the 5' non-HMG box region of the SRY gene in
      a patient with partial gonadal dysgenesis and his normal male relatives.
AB  - Mutations in the sex-determining region of the Y chromosome (the SRY gene) have
      been reported in low frequency in patients with 46,XY gonadal dysgenesis. We
      investigated 21 Brazilian 46,XY sex-reversed patients, who presented either
      complete or partial gonadal dysgenesis or embryonic testicular regression
      syndrome. Using Southern blotting, polymerase chain reaction, denaturing gradient
      gel electrophoresis and direct sequencing, we analyzed deletions and point
      mutations in the SRY gene. We found a missense mutation at codon 18 upstream of
      the 5' border of the HMG box of the SRY gene in one patient with partial gonadal
      dysgenesis. This variant sequence was also found in DNA obtained from blood and
      sperm cells of his father and in blood cells of his normal brother. The S18N
      mutation was not found in 50 normal males, ruling out the possibility of a common
      polymorphism. We identified a novel familial missense mutation (S18N) in the 5'
      non-HMG box of the SRY gene in 1 of 21 patients with 46,XY sex reversal.

PMID- 9521593
TI  - Novel and recurrent mutations in the PKD1 (polycystic kidney disease) gene.
AB  - A search has been conducted for disease-causing mutations in the PKD1 gene in 147
      unrelated ADPKD index cases. Using the polymerase chain reaction with primer
      pairs located in the 3' single copy region of the gene and single-strand
      conformation polymorphism analysis, we detected novel aberrant bands in five
      individuals that were absent in 100 control samples. Sequencing revealed three
      nonsense mutations (Q4010X, E4024X, Q4041X), a frameshift mutation (12262 del 2
      bp), and a missense mutation (G4031D). In addition, three polymorphisms were
      detected [12346 + 19delG, heterozygosity (0.13), I4044V (0.23), 12212-34C > A
      (0.07)]. The mutational mechanism for the recurrent mutation (Q4041X) is likely
      to be slipped mispairing of an adjacent direct imperfect repeat sequence.

PMID- 9521594
TI  - Localisation of receptor interacting protein 140 (RIP140) within 100 kb of D21S13
      on 21q11, a gene-poor region of the human genome.
AB  - Human chromosome 21 is the smallest and one of the most intensively studied
      autosomes. The generation of high quality genetic and physical maps for the long
      arm has enabled the research community to accelerate gene discovery and the
      identification of disease loci on the chromosome. However, the emerging pattern
      from large-scale transcriptional mapping from many groups suggests that the
      majority of the 600-1000 genes predicted to reside on the chromosome are
      clustered in two distinct regions of the long arm, on distal 21q22.1 and 21q22.3.
      Here, we report the mapping of the gene for receptor interacting protein 140
      (RIP140) on 21q11 by means of YACs, PACs and hybrid cell lines. We have placed
      RIP140 within 100 kb of D21S13, in a region of the chromosome where only one
      other gene has been described to date. The association of the RIP140 protein with
      the superfamily of nuclear receptors may be of significance in studies of trisomy
      21 (Down syndrome) and Alzheimers disease, since a modifier locus has been
      speculated to reside on 21q11.

PMID- 9521596
TI  - Polarity of mutations in tumor-associated microsatellite instability.
AB  - Many factors have been implicated in influencing the rate of microsatellite
      mutations, including the length and base composition of the repeat motif, number
      of repeats, base composition of flanking sequences and, perhaps most importantly,
      degree of perfection of the repeats. The latter is of clinical relevance, since
      in both spino-cerebellar ataxia and fragile X syndrome, alleles with imperfect
      repeats appear to be much more stable than perfect ones. As yet, the relative
      importance of increased replication slippage and decreased mismatch repair
      efficiency in the preference of mutations to occur within perfect repeats has not
      been fully determined. D13S308E is an asymmetric trinucleotide repeat
      microsatellite with the sequence (CAT)3CAC(CAT)CAC(CAT)2CAC(CAT)CAC(CAT)15, thus
      containing two parts: an 11-repeat imperfect portion (underlined above) and a 15
      repeat perfect one (bold). We sequenced eight new mutant alleles of D13S308E from
      three human gastric tumors with instability in this and other microsatellites. In
      all mutations the size variation occurred exclusively in the perfect part of the
      microsatellite. These results constitute direct evidence that the molecular basis
      of microsatellite alterations seen in normal cells is similar to those that occur
      in human tumors with extensive microsatellite instability. The investigation of
      mechanisms involved in microsatellite mutations has been handicapped by the fact
      that they are rare events. The microsatellite instability observed in malignant
      tumors provides us with a useful general system to study these mechanisms.

PMID- 9521595
TI  - Analysis of the CFTR gene in Turkish cystic fibrosis patients: identification of
      three novel mutations (3172delAC, P1013L and M1028I).
AB  - In order to determine the spectrum of cystic fibrosis (CF) mutations in the
      Turkish population, a complete coding region of the cystic fibrosis transmembrane
      conductance regulator (CFTR) gene including exon-intron boundaries, on 122
      unrelated CF chromosomes from 73 Turkish CF families was analysed by denaturing
      gradient gel electrophoresis and multiplex heteroduplex analysis on MDE gel
      matrix. In addition to 15 previously reported mutations and 12 polymorphisms,
      three novel mutations, namely 3172delAC, P1013L and M1028I, were detected.
      DeltaF508 was found to be present on 18.8% of CF chromosomes. The second most
      common mutation was 1677delTA, with a frequency of 7.3%, followed by G542X and
      2183AA-->G mutations, with frequencies of 4.9%. These four most common mutations
      in Turkish CF population account for approximately 36% of mutations. This study
      could only detect 52.5% of disease-causing mutations in this population; 47.5% of
      CF alleles remain to be identified, reflecting the high molecular heterogeneity
      of the Turkish population.

PMID- 9521597
TI  - Linkage between atopy and the IgE high-affinity receptor gene at 11q13 in atopic
      dermatitis families.
AB  - Atopic dermatitis is a common skin disease frequently associated with allergic
      disorders such as allergic rhinitis and asthma. Controversial linkage findings
      between atopy and markers at chromosome 11q13 led us to search chromosome 11 for
      genes conferring susceptibility to atopic dermatitis and atopy. Twelve families
      were investigated using highly polymorphic markers and a powerful model-free
      linkage test. Two markers gave evidence for linkage, D11S903 (P = 0.02) and
      FCER1B (P = 0.005). A two-point lod-score analysis between these two markers
      revealed significant evidence for linkage (zmax = 4.02 at (theta = 0.0). In
      regard to model-dependent lod-score analyses between atopic disorders and FCER1B,
      two-point analysis gave a lod score of z = 0.78 whereas two-locus analysis using
      a recessive-dominant mode of inheritance displayed a significant lod score of z =
      3.55. Only 2 of 12 families showed evidence for linkage using the latter
      oligogenic model. In conclusion, the results of our study map the FCER1B gene in
      close proximity to D11S903, support the finding of Cookson et al. implicating the
      IgE high-affinity receptor gene (FCER1B) at 11q13, and furthermore suggest an
      oligogenic mode of inheritance as well as heterogeneity in the genetic
      susceptibility to atopy and atopic dermatitis.

PMID- 9521599
TI  - Gene symbol: NF2. Disease: neurofibromatosis 2.

PMID- 9521598
TI  - Structure and dynamics of human interphase chromosome territories in vivo.
AB  - A new approach is presented which allows the in vivo visualization of individual
      chromosome territories in the nuclei of living human cells. The fluorescent
      thymidine analog Cy3-AP3-dUTP was microinjected into the nuclei of cultured human
      cells, such as human diploid fibroblasts, HeLa cells and neuroblastoma cells. The
      fluorescent analog was incorporated during S-phase into the replicating genomic
      DNA. Labelled cells were further cultivated for several cell cycles in normal
      medium. This well-known scheme yielded sister chromatid labelling. Random
      segregation of labelled and unlabelled chromatids into daughter nuclei resulted
      in nuclei exhibiting individual in vivo detectable chromatid territories. The
      territories were composed of subcompartments with diameters ranging between
      approximately 400 and 800 nm which we refer to as subchromosomal foci. Time
      resolved in vivo studies demonstrated changes of positioning and shape of
      territories and subchromosomal foci. The hypothesis that subchromosomal foci
      persist as functionally distinct entities was supported by double labelling of
      chromatin with CldU and IdU, respectively, at early and late S-phase and
      subsequent cultivation of corresponding cells for 5-10 cell cycles before
      fixation and immunocytochemical detection. This scheme yielded segregated
      chromatid territories with distinctly separated subchromosomal foci composed of
      either early- or late-replicating chromatin. The size range of subchromosomal
      foci was similar after shorter (2 h) and longer (16 h) labelling periods and was
      observed in nuclei of both living and fixed cells, suggesting their structural
      identity. A possible functional relevance of chromosome territory
      compartmentalization into subchromosomal foci is discussed in the context of
      present models of interphase chromosome and nuclear architecture.

PMID- 9521600
TI  - Altered peptide ligand modulation of experimental allergic encephalomyelitis:
      immune responses within the CNS.
AB  - An altered peptide ligand (analog) of the encephalitogenic epitope of proteolipid
      protein residues 139-151 (p139-151) in which residues 144 and 147 are substituted
      with leucine and arginine, respectively (LR), protects from clinical but not
      histological experimental allergic encephalomyelitis (EAE). To understand in situ
      events associated with this protection, T cells from brains of mice immunized
      with either native p139-151, the analog LR or a combination of the two were
      isolated and characterized. High proportions of cells from co-immunized mice
      (38%) and LR-immunized mice (58%) reacted to both p139-151 and LR, whereas fewer
      cells from p139-151 immunized mice (7%) were cross-reactive. T cell clones
      derived from brains of LR- and co-immunized mice were also cross-reactive in
      vitro. By reverse transcriptase-based polymerase chain reaction, higher levels of
      TGF-beta mRNA, and lower levels of TNF-alpha and IFN-gamma mRNA were found in the
      central nervous system (CNS) tissue of LR and co-immunized mice.
      Immunohistochemistry demonstrated greater TGF-beta immunoreactivity in CNS
      inflammatory foci in co-immunized and LR-immunized mice. There were no
      significant differences in CD4+ or CD8+ cell infiltrates among the groups and
      differences in other cytokines were not identified by immunocytochemistry.
      Protection from clinical EAE in LR and co-immunized mice was partially abolished
      by anti-TGF-beta antibody treatment. Thus, protection from clinical disease
      following immunization with the analog LR is associated with infiltration into
      the CNS of a T cell population that could potentially recognize the native PLP
      peptide and with enhanced TGF-beta production by cells within CNS inflammatory
      foci.

PMID- 9521601
TI  - Enhancement of expression of inducible NO synthase and inhibition of DNA
      synthesis in rat thymocytes by in vivo hydrocortisone treatment.
AB  - Glucocorticoids (GC) are known to inhibit the mitogen-induced proliferation of T
      cells. Some of the effects of GC have been ascribed to the inhibition of nitrogen
      monoxide (NO) production, since NO is involved in the effecter function of
      phagocytic cells. Although the effects of GC in vitro on thymocytes are known,
      the effect of in vivo GC treatment on proliferation and NO synthesis in
      thymocytes has not been clarified. In this study, we investigated the effects of
      the administration of hydrocortisone succinate (HC), a potent anti-inflammatory
      GC, in Sprague-Dawley rats by s.c. injection (100 mg/kg). A substantial reduction
      of concanavalin A (Con A)-stimulated [3H]thymidine incorporation was observed in
      the thymocytes from HC-treated rats. This effect was accompanied by an increase
      in the Con A-stimulated expression of the inducible type of nitric oxide synthase
      (iNOS) and nitrite accumulation. The constitutive type of NOS (cNOS) in
      thymocytes did not change during the course of in vivo HC treatment. Addition of
      NO donors, which stimulated cyclic GMP accumulation, to rat thymocytes in vitro
      inhibited Con A-stimulated DNA synthesis. Addition of dibutyryl cyclic GMP, a
      membrane permeable analog, also inhibited DNA synthesis. Co-culture with
      N(G)monomethyl-L-arginine, an inhibitor of NOS, recovered Con A-stimulated
      [3H]thymidine incorporation in the thymocytes from HC-treated rats. These
      findings suggest that NO and cyclic GMP inhibited DNA synthesis in rat thymocytes
      and that HC treatment in vivo inhibited DNA synthesis via the expression of the
      iNOS protein, and the accumulation of NO and cyclic GMP. Although it is known
      that GC regulate iNOS expression negatively in several types of cells in vitro,
      GC treatment in vivo regulates iNOS protein expression positively in rat
      thymocytes.

PMID- 9521603
TI  - Rat lymphocytes produce and secrete acetylcholine in dependence of
      differentiation and activation.
AB  - Previous data from this laboratory suggested for the first time that immune cells
      of the immune system of different species are capable to synthesize the
      neurotransmitter acetylcholine. In the present study we detected the RNA message
      for choline acetyltransferase in thymic, splenic and peripheral blood lymphocytes
      of rats using RT-PCR. Furthermore, using a sensitive radioimmunoassay, we
      measured acetylcholine in thymic, splenic and peripheral blood lymphocytes. T
      cells were found to contain about three times the amount of acetylcholine as
      compared to B-cells, and CD4+ cells showed significantly higher levels as
      compared to CD8+ cells. Mitogenic stimulation with PHA increased the
      acetylcholine levels in lymphoid cells as well as the release into the
      supernatants.

PMID- 9521602
TI  - Functional IL-4 receptors on mouse astrocytes: IL-4 inhibits astrocyte activation
      and induces NGF secretion.
AB  - IL-4 is a Th2-derived cytokine which plays an important role in the function of
      various immunocompetent cells as well as in the pathophysiology of various CNS
      disorders. In this study we characterized the expression of IL-4R in cultured
      astrocytes and explored the effects of IL-4 on the function of these cells. We
      found that astrocytes express the mRNA of both the membrane-bound and the soluble
      forms of the IL-4R, whereas they do not secrete IL-4. IL-4 inhibited both NO
      production and iNOS expression induced by LPS stimulation and decreased the
      secretion of TNF-alpha and the expression of ICAM-1. In contrast, IL-4 induced
      the secretion of NGF by astrocytes and synergized with LPS and TNF-alpha in this
      effect. These results suggest an important role for IL-4 as an immunosuppressive
      and a neurotrophic factor in the CNS.

PMID- 9521604
TI  - Interferon-gamma antagonizes transforming growth factor-beta2-mediated
      immunosuppression in murine Toxoplasma encephalitis.
AB  - The in vivo modulating activity of recombinant transforming growth factor (TGF)
      beta2 on acute toxoplasmosis was evaluated in both Toxoplasma gondii susceptible
      C57BL/6 and resistant BALB/c mice. TGF-beta2 lethally exacerbated Toxoplasma
      encephalitis in C57BL/6, but not in BALB/c mice. In C57BL/6 mice, TGF-beta2
      induced a profound dose-dependent increase of the intracerebral parasitic load as
      well as a reduction of IFN-gamma levels in serum and cerebrospinal fluid with a
      coincident decrease of MHC class II antigen expression of macrophages, microglial
      cells, and B cells. Furthermore, TGF-beta2-treated C57BL/6 mice showed a reduced
      activation of CD4+ and CD8+ T cells and a diminished recruitment of immune cells
      to the brain. The TGF-beta2-mediated development of lethal toxoplasmosis in
      C57BL/6 mice was abolished by treatment with recombinant interferon (IFN)-gamma.

PMID- 9521605
TI  - Primary sensory neurons migrate in response to the chemokine RANTES.
AB  - We examined the potential for the C-C chemokine RANTES to stimulate dorsal root
      ganglia (DRG) cell migration. Embryonic day 12 (E12.5) mouse DRG cells migrated
      in response to RANTES, in vitro, differentiating to the nociceptive phenotype
      within 18 h. In addition, RANTES stimulated intracellular calcium mobilization in
      DRG cells. RANTES expression was demonstrated by polymerase chain reaction
      analysis to be present in E10.5 limb bud, E12.5 DRG, Schwann cells, spinal cord
      and skin. RANTES protein was detected immunohistochemically in E12.5 DRG and the
      cutaneous layers of the developing hind limb. Thus, RANTES expression is
      spatially and temporally consistent with an effector molecule in sensory
      neuropoiesis, potentially expanding the role of this chemokine to include
      neurotropism.

PMID- 9521606
TI  - Evidence for deficiencies in intracerebral cytokine production, adhesion molecule
      induction, and T cell recruitment in herpes simplex virus type-2 infected mice.
AB  - We examined the intracerebral T cell response in mice infected with neurovirulent
      HSV-2 strains and an avirulent HSV-1. In HSV-2-infected brains, (i) IL-1beta, TNF
      alpha and IFN-gamma mRNA expression was low, (ii) ICAM-1 and VCAM-1 were not
      induced, (iii) few CD4+ or CD8+ cells were detected. By contrast, in HSV-1
      infected brains, (i) cytokine mRNA expression was high, (ii) adhesion molecules
      were strongly expressed, (iii) many T cells were detected. We suggest that
      deficient T cell extravasation into HSV-2-infected brain regions is caused by
      negligible ICAM-1 and VCAM-1 expression, which is due to low expression of
      critical cytokines.

PMID- 9521607
TI  - Evidence that deficient IFN-gamma production is a biological basis of herpes
      simplex virus type-2 neurovirulence.
AB  - Although immune response control of herpes simplex virus (HSV) has been well
      demonstrated, numerous HSV-2 strains are neurovirulent in immunocompetent mice.
      Using an RNase protection assay and an ELISA, we found that HSV-2-infected mice
      exhibited a deficient IFN-gamma response, an inability to clear virus, and
      eventual death. An HSV-based amplicon vector expressing mouse IFN-gamma was
      constructed and packaged into HSV-1-helper virus (HSV(pIFN-gamma)). In mice
      treated with HSV(pIFN-gamma), (i) the LD50 of HSV-2(G) increased 5000-fold, (ii)
      intracerebral IFN-gamma expression increased 10-fold, and (iii) HSV titer rapidly
      decreased. We suggest that the deficient IFN-gamma response is a basis for HSV-2
      neurovirulence in mice.

PMID- 9521608
TI  - Polymorphisms in IL-1beta and IL-1 receptor antagonist genes are associated with
      myasthenia gravis.
AB  - Interleukin 1 (IL-1)beta, TaqI restriction fragment length polymorphism (RFLP) in
      exon 5 and IL-1 receptor antagonist (IL-1Ra) polymorphism, variable numbers of an
      86-bp tandem repeat (VNTR), were analysed in 107 patients with myasthenia gravis
      (MG) and 82 ethnically matched healthy control (HC) individuals. Positive
      association was found with IL-1beta TaqI RFLP allele 2 carriage in MG (OR =
      2.007), while allele 1 was negatively associated with MG (OR = 0.498). When
      homozygous individuals for allele 2 were considered, the association was stronger
      (OR = 4.630), indicating a dose effect of allele 2. Analysis of IL-1beta TaqI
      RFLP in relation to HLA-B8 demonstrated that the allelic association was more
      pronounced in patients without HLA-B8 (OR = 2.813). There was no difference in IL
      1Ra VNTR allelic distribution in MG patients compared with HC. However, MG
      patients who were noncarriers of IL-Ra allele 2 had a significantly higher
      percentage of IL-1beta TaqI RFLP allele 2 carriage (OR = 3.085), while there was
      no such difference in IL-1Ra allele 2 carriers. Our results demonstrate a new
      genetic marker in MG, which exerts its maximum effect in patients with the lowest
      MHC-associated susceptibility. We propose a possible pathogenetic role of IL
      1beta and a possible intrinsic dyregulation of IL-1 in MG.

PMID- 9521610
TI  - The role of microglia and tumor-primed lymphocytes in the interaction between T
      lymphocytes and brain endothelial cells.
AB  - We investigated the role of IFN-gamma activated microglia in the passage of T
      lymphocytes across a monolayer of brain endothelial cells (EC) in vitro.
      Microglia isolated from Fisher 344 (F344) newborn rats were stimulated with IFN
      gamma (100 U/ml) for 48 h. T lymphocytes primed with glioma cells were 51Cr
      labeled, and added to the monolayer of F344 brain EC. In the adhesion assay, when
      EC were cultured in medium containing the supernatant of reactive microglia
      before the assay was carried out, the number of T lymphocytes adhering was
      increased. In addition, this adhesion was blocked by the addition of anti-ICAM-1
      mAb to the EC. In the migration assay, performed using the double chamber system,
      when reactive microglia adhered to the other side of EC, the number of T
      lymphocytes migrating to the underwell was also increased. When T lymphocytes
      were primed to tumor cells in vivo, both their adhesion and migration were
      enhanced. These results suggest that some soluble factors from reactive microglia
      are capable of enhancing the expression of ICAM-1 on the brain EC. As a
      consequence, large numbers of tumor-primed T lymphocytes can adhere to EC and
      migrate across the EC monolayer.

PMID- 9521609
TI  - Nitric oxide synthase inhibitor, aminoguanidine, reduces inflammation and
      demyelination produced by Theiler's virus infection.
AB  - This study evaluated effects of the inducible nitric oxide synthase (iNOS)
      inhibitor, aminoguanidine (AG), on the neuropathology and clinical disease
      produced by Theiler's murine encephalomyelitis virus (TMEV) DA strain infection.
      Treatment with AG was started on day 7, 14, 28 or 66 post-inoculation and
      continued for a minimum of 21 days. Inflammation, demyelination and axonal
      necrosis were scored in a blinded fashion on spinal cord sections from each
      mouse. Reduction in inflammation, demyelination and axonal necrosis was observed
      in mice treated with AG. Apoptosis within the spinal cord parenchyma and
      perivascular cuffs was significantly decreased. AG treatment resulted in delayed
      onset of clinical disease.

PMID- 9521611
TI  - Striational autoantibodies in myasthenia gravis patients recognize I-band titin
      epitopes.
AB  - Myasthenia gravis (MG) patients develop autoantibodies primarily against the
      acetylcholine receptor in the motor endplate, but also against intracellular
      striated muscle proteins, notably titin, the giant elastic protein of the
      myofibrillar cytoskeleton. Titin antibodies have previously been shown to be
      directed against a single epitope on the molecule, located at the A-band/I-band
      junction and referred to as the main immunogenic region (MIR) of titin. By using
      immunofluorescence microscopy on stretched single myofibrils, we now report that
      approximately 40% of the sera from 18 MG/thymoma patients and 8 late-onset MG
      patients with thymus atrophy contain antibodies that bind to a more central I
      band titin region. This region consists of homologous immunoglobulin domains and
      is known to be differentially spliced dependent on muscle type. All patients with
      I-band titin antibodies also had antibodies against the MIR. Although a
      statistically significant correlation between the occurrence of I-band titin
      antibodies and MG severity was not apparent, the results could hint at an initial
      immunoreactivity to titin's MIR, followed by reactivity along the titin molecule
      in the course of the disease.

PMID- 9521612
TI  - Effects of an anti-IL-10 monoclonal antibody on rIFNbeta-1b-mediated immune
      modulation. Relevance to multiple sclerosis.
AB  - The mechanism of action of recombinant IFNbeta1b (IFNbeta-1b), as a therapy for
      multiple sclerosis (MS), is still unknown but may result from the enhancement of
      ConA-induced suppressor cell function and the inhibition of IFNgamma secretion by
      lymphocytes. We previously demonstrated that IFNbeta-1b stimulated modest amounts
      of IL-10 secretion by monocytes and IL-10 activity, as cytokine synthesis
      inhibitory factor, was normal in MS. To determine whether IL-10 plays a role in
      IFNbeta-1b modulation of immune function in MS, we studied ConA-induced
      suppressor cell function and IFNgamma production in presence of IFNbeta-1b and an
      anti-IL-10 monoclonal antibody (mAb). Anti-IL-10 mAb significantly reduced the
      effect of IFNbeta-1b on ConA-induced suppressor cell function and IFNgamma
      production in healthy subjects; MS patients showed a trend of inhibition. We
      hypothesized that IL-10 may play a role in mediating the effects of IFNbeta-1b on
      suppressor cell function and IFNgamma production but suppressor molecules other
      than IL-10 could be also involved.

PMID- 9521613
TI  - Antibodies to gangliosides and galactocerebroside in patients with Guillain-Barre
      syndrome with preceding Campylobacter jejuni and other identified infections.
AB  - The relationship between preceding infections and antibodies to glycolipids was
      investigated in 205 Japanese patients with Guillain-Barre syndrome (GBS).
      Serological evidence of recent Campylobacter jejuni (C. jejuni) infection was
      found in 45% of the patients, compared with 1% in healthy controls. In contrast,
      recent infection of cytomegalovirus (CMV), Mycoplasma pneumoniae (M. pneumoniae)
      and Epstein-Barr virus (EBV) was detected in only 5%, 2% and none of the
      patients, respectively. C. jejuni-associated GBS was more frequent in early
      spring than in other seasons. All stool specimens positive for C. jejuni
      isolation were obtained within 10 days after the onset of GBS symptoms. Of 13 C.
      jejuni isolates from GBS patients, 10 (77%) belonged to Penner serotype 19 (heat
      stable, HS-19). Elevated titers of anti-GM1 antibody were found in 8 (80%) of 10
      GBS patients whose C. jejuni isolates belonged to HS-19 and in none of those
      infected with non-HS-19 C. jejuni (P = 0.04), and in 49% of 92 patients with C.
      jejuni infection and 25% of patients without infection of C. jejuni, CMV, EBV, or
      M. pneumoniae (P = 0.0007). The frequencies of elevated antibody titers to GD1a,
      GD1b and GQ1b were also significantly higher in GBS patients associated with C.
      jejuni than those not associated with C. jejuni, CMV, EBV, and M. pneumoniae. GBS
      in Japan seems to be associated more frequently with C. jejuni and less
      frequently with CMV than in Europe and North America.

PMID- 9521614
TI  - Substance P induces secretion of immunomodulatory cytokines by human astrocytoma
      cells.
AB  - In human astrocytoma cell lines, substance P (SP) stimulated interleukin (IL)-8,
      IL-6, granulocyte macrophage colony-stimulating factor and leukemia inhibitory
      factor protein secretion. These SP effects were blocked by a specific NK1
      tachykinin receptor antagonist. Further, SP stimulation increased the half-life
      of IL-6 and IL-8 messenger RNAs, suggesting that the synthesis of these cytokines
      is also regulated post-transcriptionally. SP-induced cytokine release was
      inhibited by staurosporine and phorbol 12-myristate 13-acetate desensitization
      suggesting protein kinase C involvement. The demonstration that SP affects
      cytokine production in glioma cells might be of relevance for the biology of such
      tumors.

PMID- 9521615
TI  - Close association of IgA anti-ganglioside antibodies with antecedent
      Campylobacter jejuni infection in Guillain-Barre and Fisher's syndromes.
AB  - IgA has an important function in the gastrointestinal immune system. We
      investigated IgA anti-ganglioside antibodies in Guillain-Barre syndrome (GBS) and
      Fisher's syndrome (FS) subsequent to Campylobacter jejuni enteritis. In previous
      studies, serological diagnosis of C. jejuni infection was based on the detection
      of IgG, IgA, and IgM anti-C. jejuni antibodies. Our study, however, showed that
      the detection of IgG anti-C. jejuni antibody alone was sufficient for the
      serological diagnosis of antecedent C. jejuni enteritis in GBS and FS, when the
      cut-off level was defined for results of sera from C. jejuni-isolated patients.
      Serological evidence of C. jejuni infection was found in 62 (31%) of 201 GBS
      patients and 12 (18%) of 65 FS patients. IgA anti-GMI antibody was detected in
      sera from 33 (16%) of the GBS patients, 1 (2%) of the FS patients, and none of
      the 46 normal control subjects. IgA anti-GM1 antibody titers were significantly
      higher in the GBS patients with positive C. jejuni serology than in those with
      negative serology (P < 0.0001) or the FS patients with positive C. jejuni
      serology (P = 0.007). IgA anti-GQ1b antibody was detected in sera from 18 (28%)
      of the FS patients, 9 (4%) of the GBS patients, and none of the normal control
      subjects. FS patients with positive C. jejuni serology had significantly higher
      titers of IgA anti-GQ1b antibody than those with negative serology (P = 0.01) or
      the GBS patients with positive C. jejuni serology (P < 0.0001). We conclude that
      anti-GM1 and anti-GQ1b IgA antibodies are closely associated with antecedent C.
      jejuni enteritis in GBS and FS, respectively.

PMID- 9521616
TI  - Restoration of sympathetic noradrenergic nerve fibers in the spleen by low doses
      of L-deprenyl treatment in young sympathectomized and old Fischer 344 rats.
AB  - It is well-established that noradrenergic (NA) nerve fibers in spleen and lymph
      nodes influence cell-mediated immune responses. Such responses are diminished in
      young animals following chemical sympathectomy and in older animals accompanying
      an age-related decline in NA nerve fibers in spleen and lymph nodes. The purpose
      of this study was to determine whether treatment with deprenyl, an irreversible
      monoamine oxidase-B (MAO-B) inhibitor, would hasten the process of splenic NA
      reinnervation following chemical sympathectomy in young rats and would reverse
      the age-related loss of sympathetic NA fibers in the spleen of old rats. To
      examine the effects of deprenyl in young sympathectomized rats, 3-month-old male
      Fischer 344 (F344) rats were treated with 6-hydroxydopamine (6-OHDA) and
      administered 0, 0.25, 1.0, 2.5, or 5.0 mg deprenyl/kg body weight (BW)/day
      intraperitoneally (i.p.) for 1, 15, or 30 days. In another study, 21-month-old
      male F344 rats were treated with 0, 0.25, or 1.0 mg deprenyl/kg BW/day i.p. for 9
      weeks. At the end of the treatment period, spleens were removed and NA
      innervation was assessed by fluorescence histochemistry, immunocytochemistry, and
      quantitation of norepinephrine (NE) by high performance liquid chromatography
      with electrochemical detection (HPLC-EC). In the spleens of young
      sympathectomized rats, there was faint fluorescence or absence of fluorescence
      and tyrosine hydroxylase-positive (TH+) fibers around the central arteriole and
      in the periarteriolar lymphatic sheath of the white pulp one day after
      administration of 6-OHDA, indicating a severe loss of NA innervation compared
      with unlesioned control animals. Treatment of sympathectomized rats with 1.0 mg,
      2.5 mg, and 5.0 mg/kg deprenyl for 30 days increased the density of NA
      innervation estimated by both fluorescence histochemistry and immunocytochemistry
      compared with vehicle-treated controls recovering spontaneously from 6-OHDA.
      Splenic NE concentration was increased in the hilar region of sympathectomized
      rats treated with 2.5 mg and 1.0 mg/kg deprenyl after 15 and 30 days,
      respectively, compared with untreated and vehicle-treated sympathectomized rats.
      The spleens of untreated and saline-treated old rats showed a reduction in the
      density of NA innervation in the white pulp compared with young animals.
      Treatment of old rats for 9 weeks with 1.0 mg/kg deprenyl induced moderate to
      intense fluorescent fibers and linear TH+ nerve fibers around the central
      arteriole and in other compartments of the white pulp, and increased splenic NE
      concentration in the hilar region and NE content in the whole spleen. Taken
      together, these results provide strong evidence for a neurorestorative property
      of deprenyl on sympathetic NA innervation of the spleen, which may lead to an
      improvement in cell-mediated immune responses.

PMID- 9521617
TI  - Golli-MBP gene in multiple sclerosis susceptibility.
AB  - Multiple sclerosis (MS) is an oligo- or polygenic disease but no specific
      susceptibility genes have been identified so far. In the Finnish population we
      have previously found evidence for linkage between MS and the myelin basic
      protein gene (here called Golli-MBP gene) suggesting that either Golli-MBP or
      another gene in its vicinity contributes to MS suceptibility. Here we have
      screened the Golli-MBP gene for nucleotide variations and carried out multipoint
      association analyses in a Finnish case-control data-set as well as in an
      independent data-set composed of 151 MS families from Finland and Sweden. In both
      data-sets we found association between MS and alleles in the 1.27 kilobase (kb)
      range at a tetranucleotide repeat element (TGGA)n which is located 1 kb upstream
      of the MBP exon 1. Haplotype analyses suggested that the MS-associated 1.27 kb
      alleles can be split into predisposing and non-predisposing variants and provided
      evidence that the candidate DNA region contributing to MS susceptibility should
      be located at the Golli-MBP gene within a 20-25 kb segment that was conserved in
      the predisposing haplotypes. These findings suggest a role for the Golli-MBP
      locus in MS susceptibility, at least in a subset of patients, and serve as a
      basis for highly focused attempts to identify predisposing mutation(s).

PMID- 9521618
TI  - CD95 expression and CD95-mediated apoptosis of T cells in multiple sclerosis. No
      differences from normal individuals and no relation to HLA-DR2.
AB  - CD95-mediated apoptosis is a potent endogenous pathway of T cell elimination that
      has been suggested to be altered in multiple sclerosis (MS). MS is associated
      with the HLA-DR2, Dw2, DQ6 HLA class II haplotype. We have previously reported
      that T cell lines from HLA-DR2-positive individuals show enhanced production of
      tumor necrosis factor (TNF), a cytokine homologous to CD95 ligand, in response to
      specific antigen. Here we have studied CD95 expression and susceptibility to CD95
      mediated apoptosis in peripheral blood mononuclear cells (PBMC) and activated T
      cells of 20 healthy individuals and 20 MS patients, half of whom were HLA-DR2
      positive. MS patients did not differ from healthy individuals in either
      parameter. There was also no difference in CD95 expression or CD95-mediated
      apoptosis when MS patients and healthy individuals were grouped and compared
      according to HLA-DR status. These data reveal no differential regulation of
      PBMC/T cell apoptosis induced by CD95 receptor ligation in MS and show no impact
      of HLA-DR2 status on PBMC/T cell susceptibility to the same apoptotic stimulus.
      However, to assess the contribution of T cell apoptosis to the pathogenesis of MS
      further studies on other details of the complex system leading to T cell
      apoptosis are required.

PMID- 9521619
TI  - FcgammaRIIA and FcgammaRIIIB polymorphisms in myasthenia gravis.
AB  - The Fcgamma receptors, FcgammaRIIA and FcgammaRIIIB contain polymorphisms with
      different capacity for IgG binding and phagocytosis. Thirty myasthenia gravis
      (MG) patients and 49 healthy controls were genotyped for the FcgammaRIIA and
      FcgammaRIIIB polymorphisms using polymerase chain reaction. The frequency of the
      FcgammaRIIA-H/H genotype was increased in thymoma MG patients compared to other
      MG patients (P = 0.05) and controls (P = 0.02). The distribution of FcgammaRIIIB
      alleles in MG patients did not differ from the controls, but MG patients with the
      NA1/NA1 genotype had the most severe MG (P = 0.01). Levels of AChR-antibodies and
      frequency of titin or ryanodine receptor antibodies were not associated with the
      FcgammaRIIA or FcgammaRIIIB genotypes. The results suggest different pathogenetic
      mechanisms in paraneoplastic and non-paraneoplastic autoimmune MG.

PMID- 9521620
TI  - The role of regulatory T cells in Lewis rats resistant to EAE.
AB  - Adult Lewis (LEW) rats are highly susceptible to experimental autoimmune
      encephalomyelitis (EAE), induced actively by immunization with guinea pig (GP)
      myelin basic protein (MBP) in complete Freund's adjuvant or adoptively
      transferred with activated T lymphocytes reactive to GP MBP peptide 68-88. Once
      LEW rats recover from active EAE or when given MBP in incomplete Freund's
      adjuvant (IFA), they become resistant to further attempts to induce active or
      passive EAE. In this study, we examined whether such EAE-resistant rats after MBP
      IFA immunization have reduced frequencies of MBP-reactive T cells, whether these
      T cells are anergized, and whether the activity of regulatory T cells is
      increased to the event that they prevent activation of MBP-specific T cell
      subpopulations. By limiting dilution analyses (LDA) of unfractionated splenic T
      cells, the levels of MBP-reactive T cells in EAE-resistant rats appeared to be
      approximately 5% of the levels in EAE-susceptible rats. However, a subsequent
      analysis of CD4+ enriched T cell populations, depleted of the CD8 subset, showed
      similar frequencies of MBP-reactive cells in susceptible and resistant LEW rats.
      Not only were the frequencies on LDA altered by suppressor cells, but also LDA
      comparisons based on cell proliferation and cytokine production as indicators of
      MBP reactive cell frequencies gave markedly different results. We conclude that
      MBP-reactive T cells in this model of EAE-resistant LEW rats are hyporeactive to
      MBP as the result of an increased activity of a regulatory subset of CD8+ T
      cells. These results also demonstrate that the quantitation of MBP-reactive CD4+
      T cells by LDA is strongly influenced by the presence of functionally
      antagonistic CD8+ T cells, which cause an underestimation of responder T cell
      frequencies, and by the method of detecting T cell reactivity.

PMID- 9521621
TI  - Distribution of nociceptin/orphanin FQ receptor transcript in human central
      nervous system and immune cells.
AB  - We have examined the distribution of the opioid receptor-like-1 (ORL-1)
      transcript in the human CNS as well as human immune cells by RT-PCR and RNAse
      protection. The hORL-1 mRNA was distributed throughout the brain and particularly
      abundant in cortical areas, striatum, thalamus and hypothalamus. In the immune
      system, gene transcription was observed in normal circulating lymphocytes and
      monocytes as well as in T, B and monocytic cell lines. A splice variant, lacking
      15 nucleotides at the junction between exon 1 and exon 2, showed a distribution
      similar to the already known ORL-1 transcript. Altogether these results show
      comparable expression levels of the hORL-1 gene in both nervous and immune
      systems, suggesting that the ORL-1-encoded receptor may participate to neuronal
      and non-neuronal physiological functions in humans.

PMID- 9521622
TI  - The role of stress hormones in exercise-induced suppression of alveolar
      macrophage antiviral function.
AB  - We hypothesized that a previously observed exercise-induced suppression of
      alveolar macrophage antiviral resistance results from increases in corticosterone
      and/or epinephrine. Mice (CD-1) were run to fatigue on a treadmill (exercise), or
      placed in Plexiglas lanes above the treadmill (control). The role of
      corticosterone was assessed by further dividing mice into groups receiving one of
      the following treatments; sham surgery, adrenalectomy, or adrenalectomy plus
      corticosterone replacement. Macrophage antiviral function was suppressed in the
      exercised mice compared to the control mice. However, macrophage antiviral
      function was not suppressed in the exercised mice that underwent adrenalectomy or
      adrenalectomy plus corticosterone replacement. We tested whether another adrenal
      factor (epinephrine) may be involved by dividing mice into exercise and control
      groups treated with either saline or propranolol. Macrophage antiviral function
      was again suppressed in the saline-treated exercised mice compared to saline
      treated control mice, but no differences were found between the exercised mice
      receiving propranolol, control mice receiving propranolol, or saline-treated
      control mice. Isoproterenol, when added to alveolar macrophages in culture, also
      suppressed antiviral resistance. These findings suggest that decreased macrophage
      antiviral function following exercise may be due to increased release of adrenal
      catecholamines.

PMID- 9521623
TI  - Aminoguanidine, a selective inhibitor of the inducible nitric oxide synthase, has
      different effects on experimental allergic encephalomyelitis in the induction and
      progression phase.
AB  - To elucidate the role of excessive nitric oxide (NO) via the inducible nitric
      oxide synthase (iNOS) in experimental allergic encephalomyelitis (EAE), the
      effect of a selective iNOS inhibitor, aminoguanidine, was investigated using mice
      with actively induced EAE. Administration of aminoguanidine by intraperitoneal or
      intracisternal injection from day 2 to day 12 after immunization produced a
      significant delay in the onset of EAE. On the other hand, administration of
      aminoguanidine by intraperitoneal or intracisternal injection for 10 days after
      the onset of EAE enhanced the clinical severity and mortality rate and hastened
      the onset of relapse significantly. The histological study at day 11 after the
      onset revealed that more inflammatory cells were present in the central nervous
      system of mice treated with aminoguanidine as compared with mice without
      aminoguanidine treatment. These results suggested that NO via iNOS was a
      pathogenetic factor in the induction phase of EAE, but had an inhibitory role in
      the progression phase of EAE. Although the effect of NO synthase inhibitors on
      EAE has been controversial, the present study suggested that the timing of
      administration might be an important consideration and might explain the previous
      contradictory reports.

PMID- 9521624
TI  - The rat dermorphin-like immunoreactivity is supported by an aminopeptidase
      resistant peptide.
AB  - Site-directed antibodies against synthetic related dermorphin peptides were
      previously produced and characterized. One of them, which specifically recognizes
      the crucial 'opioid message' (the N-terminal part of the dermorphin molecule
      (i.e. Tyr-D-Ala-Phe-Gly) was selected in order to detect and locate endogenous
      dermorphin-like molecules in rat, mouse and guinea pig tissues. Dermorphin-like
      peptides were found to be present in tissues known to contain peptides such as
      neurons in the central nervous system, nerve fibers in the gut and B and T immune
      cells. With all the tissues assayed, the HPLC profile obtained on the
      immunoreactive material showed the same main peak eluted at a retention time of
      32 +/- 1 min. The results of biochemical experiments in which enzymatic
      treatments were performed on the dermorphin-like immunoreactivity indicate the
      immunoreactivity is a peptide resistant to aminopeptidase hydrolysis. This
      finding suggests the presence of a residue conferring resistance to proteolytic
      processes of this kind, which is likely to be a D-amino acid residue.

PMID- 9521625
TI  - Mammalian zinc transporters.
AB  - Genes that are involved in mammalian zinc transport recently have been cloned.
      These all predict proteins with multiple membrane spanning regions, and most have
      a histidine-rich intracellular loop. ZnT-1 was the first cloned and is associated
      with zinc efflux. It is found in all tissues examined, and, at least in some, ZnT
      1 expression is regulated by dietary zinc intake. In enterocytes of the small
      intestine and renal tubular cells, ZnT-1 is localized to the basolateral
      membrane, suggesting an orientation that is consistent with zinc
      absorption/retention. ZnT-2 is also an exporter and may be involved in zinc
      efflux or uptake into vesicles in intestine, kidney, and testis. ZnT-3 is
      involved in zinc uptake into vesicles in neurons and possibly in testis. ZnT-4 is
      also an exporter and is highly expressed in mammary gland and brain. The divalent
      cation transporter 1 (DCT1) is regulated by iron, but exhibits transport activity
      for a number of trace elements including zinc. Description of a family of zinc
      transporters bridges the integrative and reductionist approach to the study of
      zinc metabolism. Other members of this transporter family may emerge. Many of
      these may be regulated by zinc, and some may respond to immune challenge,
      oxidative stress, and competing metals in the dietary supply. Collectively,
      description of transporters that influence cellular zinc uptake and efflux will
      provide a clearer understanding of the molecular events that regulate zinc
      absorption and homeostasis.

PMID- 9521626
TI  - Selective elevation of glutathione levels in target tissues with L-2
      oxothiazolidine-4-carboxylate (OTC) protects against hyperoxia-induced lung
      damage in protein-energy malnourished rats: implications for a new treatment
      strategy.
AB  - It has become recognized that enhancing the antioxidant defense system during the
      early phase of rehabilitation is important to the survival of wasting protein
      energy malnourished (PEM) patients. In this study, we compared the efficacy of
      dietary protein replenishment and supplementation with L-2-oxothiazolidine-4
      carboxylate (OTC, 3.5 mg/d), a cysteine precursor, to protect against hyperoxia
      induced lung damage in PEM rats. The PEM rats were produced by feeding weanling
      rats a protein-deficient diet (0.5% protein) for 14 d. PEM rats were then divided
      in three dietary treatment groups, 0.5% protein (-Pr), 0.5% protein plus the OTC
      supplement (+OTC), or 15% protein (+Pr) during 4 d of either hyperoxia (85% O2)
      or air exposure. Increased lung-to-body weight ratios, indicative of oxidative
      tissue damage, were observed following exposure to hyperoxia in -Pr and +Pr rats,
      but not in +OTC rats, even though the OTC supplement and the 15% protein diet
      contained a comparable amount of cysteine. Tissue reduced glutathione (GSH)
      status, GSH-dependent enzyme activity and antioxidant defense enzyme activities
      were monitored in the lung, liver and blood during 4 d of hyperoxia exposure. OTC
      supplementation enhanced GSH levels significantly in the lung of PEM rats,
      whereas protein repletion significantly elevated blood GSH concentrations. The
      protective effect of OTC was not a function of changes in activity of GSH
      dependent enzymes or oxygen defense enzymes in the lung. These results indicate
      that a short-term strategy that selectively elevates GSH levels in the lung is
      more effective than protein repletion in protecting against hyperoxia-induced
      oxidative lung damage in PEM rats.

PMID- 9521627
TI  - Obese gene expression in porcine adipose tissue is reduced by food deprivation
      but not by maintenance or submaintenance intake.
AB  - The relationship between obese gene expression and energy intake was determined
      in pigs of various body weights. With ad libitum consumption, expression
      increased (P < 0.001) with body weight from 55 to 163 kg. Obese mRNA relative
      abundance was correlated with fat mass (r = 0.74, P < 0.0001) and percentage of
      fat (r = 0.72, P < 0. 0001). Obese expression was also evaluated at 159 kg
      (initial weight) and ad libitum, maintenance or 23% of maintenance intake for 28
      d. Obese mRNA was independent of treatment (P > 0.78) despite considerable weight
      differences. Obese mRNA abundance was then compared at 136 kg (initial weight)
      and ad libitum or maintenance intake for 3 or 28 d. Abundance was not influenced
      by either duration of treatment or intake, despite a small increase (P < 0.01) in
      serum nonesterified fatty acids (NEFA) and a reduction (P < 0.02) in insulin
      attributable to maintenance intake. Finally, mRNA abundance was determined at 60
      and 136 kg and conditions of food deprivation or ad libitum intake for 3 d. Food
      deprivation reduced (P < 0.01) serum insulin and increased (4- to 5-fold) NEFA
      concentrations. Obese mRNA abundance was greater (P < 0.01) in the heavier pigs
      and was reduced (P < 0.01) by food deprivation. We conclude that obese mRNA
      abundance in pigs correlates with fat mass and percentage of body fat under
      conditions of ad libitum intake. Furthermore, obese mRNA abundance is reduced by
      food deprivation, whereas lesser degrees of intake restriction do not change
      obese mRNA abundance, even when accompanied by appreciable weight loss.

PMID- 9521628
TI  - Thiamine deficiency decreases steady-state transketolase and pyruvate
      dehydrogenase but not alpha-ketoglutarate dehydrogenase mRNA levels in three
      human cell types.
AB  - Reductions in the levels and activities of enzymes that utilize thiamine
      diphosphate (ThDP) as a cofactor are thought to be responsible for the tissue
      damage suffered during thiamine deficiency. Although loss of cofactor can account
      in part for loss of enzyme activity, thiamine and its phosphorylated derivatives
      may also regulate the expression of the genes encoding these proteins. To examine
      this possibility, steady-state mRNA levels for three ThDP-dependent enzymes were
      measured in human fibroblasts, lymphoblasts and neuroblastoma cells cultured
      under conditions of thiamine sufficiency and deficiency. In all three cell types,
      the mRNA levels of transketolase and the E1beta subunit of pyruvate dehydrogenase
      complex were lower in thiamine-deficient cultures. In contrast, mRNA levels for a
      ThDP-binding subunit of alpha-ketoglutarate dehydrogenase, the E1 subunit did not
      differ. These results indicate that thiamine or a thiamine metabolite regulates
      the expression in humans of some, but not all, genes encoding ThDP-utilizing
      enzymes.

PMID- 9521629
TI  - Fermentation products of sugar-beet fiber by cecal bacteria lower plasma
      cholesterol concentration in rats.
AB  - Plasma cholesterol concentration is reduced by feeding some dietary fibers but
      the mechanism is not fully understood. We examined whether cecal fermentation
      products are involved in lowering plasma cholesterol by feeding rats a highly
      fermentable sugar-beet fiber (SBF) in four separate experiments. These were
      designed to investigate the effects on plasma cholesterol of oral ingestion of
      fermentation products on plasma cholesterol, the effects of the products in
      comparison with that of a short-chain fatty acid (SCFA) mixture, effects of
      individual SCFA and effects of alteration of energy and nitrogen ratio in the
      diet by the addition of the SCFA mixture. Cecal contents of rats were cultured
      with SBF by using a jar fermenter under anaerobic conditions, and the supernatant
      from the culture medium, containing fermentation products of SBF, was collected
      and freeze-dried before feeding to rats. Yield of fermentation products as dry
      weight from the fiber was 80-90%. In rats fed a diet containing fermentation
      products (80 g/kg diet), plasma cholesterol concentrations were lower than in
      rats of the fiber-free group 3, 7 and 14 d after feeding the test diet. Major
      SCFA in the fermentation products were sodium salts of acetic, propionic and
      butyric acids. Plasma cholesterol concentration in rats fed the diet containing a
      mixture of equal amounts of the three SCFA salts (66 g/kg diet) as the
      fermentation products diet was also lower than that in the fiber-free group and
      was not different from those in rats fed SBF (100 g/kg diet) and the fermentation
      products. In rats fed an acetate-containing diet but not in rats fed diets
      without acetate, plasma cholesterol was significantly lower than in the fiber
      free group. In conclusion, absorption of SCFA from cecal fermentation products
      lowers plasma cholesterol. Acetate, and not propionate, may be responsible for
      lowering plasma cholesterol concentration.

PMID- 9521630
TI  - Alcoholic beverage consumption and lung cancer risk among residents of Los
      Angeles County.
AB  - Although studies generally support a positive association between alcohol
      consumption and lung-cancer risk, the relationship between specific alcoholic
      beverages and lung-cancer risk has been inconsistent. We examined recent and past
      alcoholic beverage intake among 261 incident cases and 615 population controls
      enrolled in a lung-cancer case-control study of African Americans and Caucasians
      in Los Angeles County between 1991 and 1994. An in-person interview elicited
      information about past alcohol intake from ages 30 to 40 y, smoking, other lung
      cancer risk factors, as well as recent intake of alcohol, and recent dietary
      intake. An association was observed between recent hard-liquor consumption and
      lung-cancer risk. The odds ratio (OR) for 1 or more drinks (1.5 oz or 0.051 mL)
      per day of hard liquor compared with infrequent liquor drinking (0-3 drinks per
      month), adjusted for smoking, the matching factors, saturated fat and other
      alcoholic beverages was 1.87 [95% confidence interval (CI) = 1.02-3.42]. No
      appreciable association was observed for total alcohol, whereas small inverse
      associations were observed for beer and wine, although confidence intervals were
      wide. An elevated lung-cancer risk was also observed for past liquor consumption
      (between ages 30 and 40 y). The adjusted OR for 1 or more drinks per day of
      liquor compared with infrequent drinkers was 1.83 (95% CI = 1. 06-3.15).
      Confounding of the association between alcohol and lung cancer by smoking was
      apparent. Although we devoted considerable efforts to adjusting for smoking in
      our analyses, residual confounding is still possible because smoking and alcohol
      are closely associated. In addition, case-control studies including this study
      should be viewed with caution because of possible selection bias. An increased
      risk of lung cancer might occur with moderate drinking of hard liquor but
      confirmation is required in larger studies.

PMID- 9521631
TI  - Adolescent obesity increases significantly in second and third generation U.S.
      immigrants: the National Longitudinal Study of Adolescent Health.
AB  - Little is known concerning obesity patterns of ethnic subpopulations in the U.S.
      and the effects of acculturation on these patterns. Adolescent obesity, a major
      public health problem, has important health, social and economic consequences for
      the adolescent. The National Longitudinal Study of Adolescent Health survey is
      unique in the size of the adolescent sample and in its ability to provide large
      representative samples of Anglo, African-American, Hispanic and Asian-American
      adolescents. A nationally representative sample of 13,783 adolescents was
      studied. Measurements of weight and height collected in the second wave of the
      survey were used to study adolescent obesity. Multivariate logit techniques were
      used to provide an understanding of the ethnic, age, gender and intergenerational
      patterns of adolescent obesity. Comparisons are presented between the NHANES III
      results and those from the Adolescent Health Survey. The smoothed version of the
      NHANES I 85th percentile cut-off was used for the measure of obesity in this
      paper. For the total sample, 26.5% were obese. The rates were as follows: white
      non-Hispanics, 24.2%; black non-Hispanics, 30.9%; all Hispanics, 30.4%; and all
      Asian-Americans, 20.6%. Important variations within the Hispanic and Asian
      American subpopulations are presented. The Chinese (15.3%) and Filipino (18.5%)
      samples showed substantially lower obesity than non-Hispanic whites. All groups
      showed more obesity among males than among females, except for blacks (27.4% for
      males and 34.0% for females). Asian-American and Hispanic adolescents born in the
      U.S. are more than twice as likely to be obese as are first generation residents
      of the 50 states.

PMID- 9521633
TI  - A prospective study of dietary fiber types and symptomatic diverticular disease
      in men.
AB  - To examine prospectively dietary fiber calculated from food composition values
      based on analytic techniques and specific dietary fiber types in relation to risk
      of diverticular disease, we analyzed data from a prospective cohort of 43,881
      U.S. male health professionals 40-75 y of age at base line; subjects were free of
      diagnosed diverticular disease, colon or rectal polyps, ulcerative colitis and
      cancer. The insoluble component of fiber was inversely associated with risk of
      diverticular disease relative risk (RR) = 0. 63, 95% confidence interval (CI),
      0.44-0.91, P for trend = 0.02, and this association was particularly strong for
      cellulose (RR = 0.52, 95% CI, 0.36-0.75, P for trend = 0.002). The association
      between diverticular disease and total dietary fiber intake calculated from the
      AOACstandards method was not appreciably different from results using the
      Southgate or Englyst method [for AOAC method, RR = 0.60, 95% CI, 0.41-0.87; for
      Southgate method, RR = 0.61, 95% CI, 0.42-0. 88; for Englyst method, RR = 0.60,
      95% CI, 0.42-0.87, for the highest quintiles]. Our findings provide evidence for
      the hypothesis that a diet high in dietary fiber decreases the risk of
      diverticular disease, and this result was not sensitive to the use of different
      analytic techniques to define dietary fiber. Our findings suggest that the
      insoluble component of fiber was significantly associated with a decreased risk
      of diverticular disease, and this inverse association was particularly strong for
      cellulose.

PMID- 9521632
TI  - Metallothionein expression is increased in monocytes and erythrocytes of young
      men during zinc supplementation.
AB  - The metallothionein gene is transcriptionally regulated by zinc. Consequently,
      metallothionein has potential for serving as an index of dietary zinc status in
      humans. To examine this possibility, an enzyme-linked immunoassay (ELISA) based
      on a sandwich approach that utilizes monoclonal and chicken egg yolk antibodies
      was used to compare the response of erythrocyte metallothionein protein levels
      with the response of monocyte metallothionein mRNA levels as measured by
      competitive reverse transcriptase-polymerase chain reaction (CRT-PCR) during zinc
      supplementation. Young male subjects participated in an 18-d supplementation
      study in which zinc was provided at 50 mg/d. Control subjects received a placebo.
      The zinc supplement resulted in significantly greater erythrocyte metallothionein
      levels by d 8 of supplementation compared with controls. Monocyte metallothionein
      mRNA levels were significantly greater than those of controls by d 2 of
      supplementation. Both remained elevated through d 18. They returned to base line
      by 8 and 4 d after supplementation, respectively. The plasma zinc concentration
      was significantly greater than in controls by d 6 and had returned to control
      levels by d 22 of supplementation. The results presented here show that both
      monocyte metallothionein mRNA and erythrocyte metallothionein protein
      concentrations change in human subjects in response to elevated dietary zinc
      intake and that monocyte metallothionein mRNA responds more rapidly to elevation
      of dietary zinc status than erythrocyte metallothionein protein. Consequently,
      both erythrocyte metallothionein and monocyte metallothionein mRNA may prove to
      be measures useful for assessment of either zinc depletion or the bioavailability
      of zinc supplements.

PMID- 9521634
TI  - Dietary supplementation with L-methionine impairs the utilization of urea
      nitrogen and increases 5-L-oxoprolinuria in normal women consuming a low protein
      diet.
AB  - Urea kinetics were measured in normal women after 5 d consuming a low protein
      diet [LP, 67 mg N/(kg.d), 0.42 g protein/(kg.d)]. To determine whether the
      availability of methionine limits the utilization of nonessential nitrogen from
      low protein diets, the study was repeated on four further occasions with the
      addition of dietary supplements of L-methionine, 9 mg N/(kg.d) (LP-M); urea, 52
      mg N/(kg.d) (LP-U); urea and methionine (LP-UM); or urea, 26 mg N/(kg.d), and
      glycine, 26 mg N/(kg.d), (LP-UG). Urea kinetics were derived after prime and
      intermittent oral doses of [15N15N]urea from the measurements of enrichment by
      isotope ratio mass spectrometry in urea isolated from urine. Nitrogen balance was
      significantly improved when the women consumed LP-U and LP-UG, but not LP-M or LP
      UM. The urinary excretion of 5-L-oxoproline was measured as a marker of glycine
      availability and was significantly lower when women consumed LP-U and LP-UG
      compared with either LP or LP-M and LP-UM. There was a significant correlation
      between urinary 5-L-oxoproline and urinary sulfate excretion (r = 0.68, P =
      0.00003). The availability of methionine was not limiting for nitrogen metabolism
      when women consumed these diets, whereas the response to supplementation with
      urea alone or urea with glycine showed that the availability of nonessential
      nitrogen was limiting. Glycine is consumed in the detoxification of excess
      methionine, and supplementation with methionine appeared to place a competitive
      demand on the availability of glycine for other metabolic processes.

PMID- 9521635
TI  - Supplementation with isoflavonoid phytoestrogens does not alter serum lipid
      concentrations: a randomized controlled trial in humans.
AB  - Isoflavonoids are a class of flavonoids that are derived in the human diet mainly
      from soybean-based foods. The major dietary isoflavonoids, genistein and
      daidzein, have estrogen-like activity and are classed as phytoestrogens. Because
      estrogens can lower serum LDL cholesterol and raise HDL cholesterol, the
      objective of this study was to determine if isoflavonoids could improve serum
      lipids in healthy subjects. Forty-six men and 13 postmenopausal women not
      receiving hormone replacement therapy completed a randomized, double-blind,
      placebo-controlled trial of two-way parallel design and 8 wk duration. One tablet
      containing 55 mg of isoflavonoids (predominantly in the form of genistein) or one
      placebo tablet was taken daily with the evening meal. Subjects maintained their
      usual diet and physical activity, which were unchanged throughout the
      intervention. Measurement of isoflavonoids and their metabolites in 24-h urine
      samples provided an assessment of compliance and of isoflavonoid metabolism.
      Serum total, LDL, HDL and HDL subclass cholesterol, triglycerides and lipoprotein
      (a) were assessed at baseline and during the last week of intervention. After
      adjustment for baseline values, no significant differences in postintervention
      serum lipid and lipoprotein (a) concentrations between groups were identified.
      Further adjustment for age, gender and weight change did not alter the results.
      In addition, changes in urinary isoflavonoids were not significantly correlated
      with changes in serum lipids and lipoprotein (a). Therefore, this study does not
      support the hypothesis that isoflavonoid phytoestrogens can improve the serum
      lipids, at least in subjects with average serum cholesterol concentrations.

PMID- 9521636
TI  - In vivo glucose contribution to glutamate synthesis is maintained while its
      contribution to acetyl CoA is lowered in adult mice fed a diet with a high
      fat:carbohydrate ratio.
AB  - To investigate the contribution of dietary carbohydrate to glutamate and acetyl
      CoA synthesis, two groups of adult mice were fed a high- (HCD) or a low
      carbohydrate diet (LCD) in which 5% of the carbohydrate was [U-13C]-glucose. Four
      animals from each dietary group were killed after 1, 2 and 5 d. The tracer:tracee
      ratios of [13C3] and [13C6]blood glucose and of the [13C2] and [13C3] isotopomers
      of blood, mucosal, hepatic and muscle alanine and glutamate were used to
      calculate the fractional contribution of glucose to the 3-carbon, acetyl CoA and
      oxaloacetate pools of each tissue. In the HCD mice, glucose contributed 66, 33
      and 31% of the acetyl CoA pool of muscle, liver and mucosa, respectively. The
      contribution of glucose to acetyl CoA was lowered by 33% (P < 0.05) and 55% (P <
      0.01) in the liver and muscle of the LCD group, respectively, but was unaltered
      in the mucosa. Glucose made a minor contribution to glutamate synthesis via
      oxaloacetate in the liver (23%) and muscle (10%) of the HCD group. The fraction
      of hepatic and muscle glutamate synthesis derived from glucose was not affected
      by the diet. We conclude that glucose oxidation in liver and muscle parallels the
      contribution of carbohydrate to dietary energy and that glucose is not a major
      carbon precursor for muscle glutamate synthesis. Net glutamate synthesis in
      extraintestinal tissues is preserved when dietary carbohydrate is restricted.

PMID- 9521637
TI  - Maternal diet fatty acid composition affects neurodevelopment in rat pups.
AB  - The effect of pre- and postnatal maternal dietary fatty acid composition on
      neurodevelopment in rat pups was studied. Timed pregnant dams were fed, beginning
      on d 2 of gestation and throughout lactation, either nonpurified diet (reference)
      or a purified diet whose fat source (22% of energy) was either corn oil or
      menhaden fish oil. On postnatal d 3, pups were randomly cross-fostered among dams
      of the same diet group and culled to 10 pups per dam. Milk was removed from
      stomachs of culled pups for fatty acid analyses. From postnatal d 4 to 30, pups
      were assessed daily for the appearance of neurodevelopmental reflexes. Auditory
      brainstem conduction times were measured on postnatal d 23 and 29. Pups were
      killed on postnatal d 30, and cerebrums were removed for fatty acid analyses. The
      fatty acid composition of maternal milk and pup cerebrums reflected maternal diet
      with higher levels of (n-3) and (n-6) fatty acids in the fish oil and corn oil
      groups, respectively. The time of appearance of auditory startle was
      significantly delayed (P = 0.004), and auditory brainstem conduction times on
      postnatal d 23 and 29 were significantly longer in pups of the fish oil- than
      corn oil-fed dams (P </= 0.05). A delay in the appearance of the auditory startle
      reflex and longer auditory brainstem conduction times in pups of dams fed fish
      oil-supplemented diet may be due to negative effects on myelination of the
      auditory brainstem pathway.

PMID- 9521638
TI  - One or more serum factors promote peptide utilization in cultured animal cells.
AB  - We have shown previously that MACT-T and C2C12 cells utilize methionine
      containing di- to octapeptides as methionine sources for protein accretion and
      cell proliferation in the presence of 60 mL/L desalted fetal bovine serum. In
      this study, serum factors that may regulate the use of peptides as amino acid
      sources in C2C12 and MAC-T cells were examined. The basal media contained
      methionine-free Dulbecco's modified Eagle's medium supplemented with 4.0 mL/L
      bovine serum lipids, 10 mL/L chemically defined lipid concentrate, bovine insulin
      (1 mg/L), 30 mL/L low protein serum replacement (LPSR-1) or 60 mL/L desalted
      animal serum. Treatment media included basal media supplemented with no
      methionine, L-methionine, or one of the methionine-containing peptides. L
      Methionine promoted protein and DNA accretion (P < 0.05) in the presence of
      desalted animal sera, insulin or LPSR-1. Methionine-containing peptides also
      promoted protein and DNA accretion (P < 0.05) in the presence of desalted animal
      sera or LPSR-1, but not with insulin, except methionylleucine. In a cell-free
      medium, fetal bovine serum hydrolyzed peptides to varying degrees. We conclude
      that animal sera contain one or more factors that regulate utilization of
      peptides as amino acid sources for C2C12 and MAC-T cells.

PMID- 9521639
TI  - Taurine status in cats is not maintained by dietary cysteinesulfinic acid.
AB  - Endogenous synthesis of taurine by cats is limited. Putative precursors of
      taurine, cysteinesulfinic acid and cysteic acid, were fed to cats to determine
      whether they were utilized. Groups of five cats were depleted of taurine by a
      resin (Colestipol(R)) diet, then given 6 dietary treatments containing (g/kg
      diet): 0.0, 0.4, or 0.8 taurine; or 0.98 or 1.96 cysteinesulfinic acid, or 0.4
      taurine + 1.0 cysteic acid for 12 wk. Plasma and whole blood taurine
      concentrations and body weights were measured weekly. Concentration of taurine in
      semitendinosus muscle was measured initially, after 2 wk of taurine depletion
      (after resin-diet), and monthly thereafter. The resin diet decreased
      concentrations of taurine in plasma, whole blood, and muscle to 0.20, 0.49, and
      0.37 of initial values, respectively. Cysteinesulfinic acid diets resulted in no
      significant (P > 0.05) increase in the concentration of taurine in plasma, whole
      blood, or muscle, and no increased excretion of cysteinesulfinate or taurine in
      urine or feces. Cats fed the diets containing 1.0 g cysteic acid + 0.4 g taurine,
      or 0.8 g taurine/kg diet had similar concentrations of taurine in plasma, whole
      blood, and muscle. Aminotransferase activity for cysteinesulfinic acid in the
      liver and intestinal mucosa of cats and rats was higher than that for aspartic or
      cysteic acids. Transamination of dietary cysteinesulfinic acid to beta
      sulfinylpyruvate (which spontaneously decomposes), rather than decarboxylation is
      postulated as the basis for no detectable conversion to taurine. In contrast,
      cysteic acid is reversibly transaminated to beta-sulfopyruvate which is stable
      and thereby is a precursor for taurine in cats.

PMID- 9521640
TI  - Chronic ethanol consumption affects glutathione status in rat liver.
AB  - There is no consensus yet on the role of oxidative stress in the nutritional
      outcome of chronic ethanol feeding and the status of cellular antioxidative
      defense systems against ethanol toxicity. In this study, chronic alcohol
      consumption in humans was reproduced in Sprague-Dawley rats to investigate the
      effect of ethanol ingestion on the regulation of oxidative stress in liver with a
      special focus on glutathione. Adult male rats were given 36% of total energy as
      alcohol in the Lieber-DeCarli liquid diet for 6 wk. The control group was pair
      fed the diet containing isocaloric dextrin-maltose instead of ethanol. Chronic
      ethanol ingestion enhanced expression of cytochrome P450 II E1 in the liver, but
      did not significantly alter either the level of hepatic thiobarbituric acid
      reactive substances or the carbonyl group content of proteins. The hepatic
      concentrations of total and reduced glutathione and the activities of catalase,
      glutathione reductase and glutathione S-transferase were significantly higher in
      the ethanol group than in the control group. The activities of glutathione
      peroxidase and glucose-6-phosphate dehydrogenase were significantly lower in the
      ethanol group than in controls. Chronic ethanol consumption by well-nourished
      rats for 6 wk increased enzyme activities related to the recycling and
      utilization of glutathione in the liver. Such an enhancement in the activities of
      the hepatic antioxidative defense system may be one of the protective mechanisms
      of the body against oxidative tissue damage caused by ethanol-induced free
      radicals.

PMID- 9521641
TI  - Iron supplementation does not affect cell proliferation or aberrant crypt foci
      development in the colon of sprague-dawley rats.
AB  - It has been suggested that high iron stores enhance colon carcinogenesis. The
      effect of high dietary iron (Fe) on indices of iron, copper (Cu) and manganese
      (Mn) status, lipid peroxidation using the thiobarbituric acid reactive substances
      assay, superoxide dismutase, glutathione peroxidase, glutathione transferase and
      ceruloplasmin activities, cell proliferation and development of preneoplastic
      lesions known as aberrant crypt foci (ACF) in rat colon was examined using a 3 x
      2 factorial design. Male weanling Sprague-Dawley rats were fed adequate (AFe; 45
      mg Fe/kg diet), moderately high (MHFe; 225 mg Fe/kg diet) and high (HFe; 450 mg
      Fe/kg diet) dietary Fe for 2.5 wk, then treated with azoxymethane (AOM; 2
      injections, 1 wk apart; total dose 30 mg/kg body weight) or saline (n = 14-15 per
      group). Dietary treatment continued for another 6 wk after the second AOM dose.
      At the time of AOM injection, colon Fe concentrations were one- and threefold
      higher for MHFe and HFe rats, respectively, than for AFe rats. It was proposed
      that high dietary Fe would adversely affect Cu and Mn status, resulting in
      impaired antioxidant enzyme activity. However, neither indices of Cu and Mn
      status nor colonic mucosal antioxidant enzyme activities were affected by dietary
      Fe except for plasma ceruloplasmin activity, which was slightly lower in rats fed
      high iron diets than in rats fed adequate iron diets (P < 0.01). Dietary Fe had
      no significant effect on colonic mucosal lipid peroxidation, cell proliferation
      or ACF development. In conclusion, our findings suggest that dietary Fe
      concentrations that are approximately 5 and 10 times adequate do not enhance
      oxidative stress, cell proliferation and ACF development in the colon of rats.

PMID- 9521642
TI  - Neurochemical changes after imbalanced diets suggest a brain circuit mediating
      anorectic responses to amino acid deficiency in rats.
AB  - Amino acid-imbalanced (IMB) diets induce an acute amino acid deficiency and
      hypophagic responses in most animals. The neural circuits underlying these
      responses are unknown. To ascertain potential neural circuits involved in the
      recognition of IMB, we measured the concentrations of norepinephrine, dopamine,
      serotonin, their metabolites and 20 amino acids in 14 rat brain areas in three
      studies. Rats were prefed a basal diet with L-amino acids as the protein source
      for at least 1 wk. For the experiments, either threonine or isoleucine IMB diet
      was offered for 2.5 or 3.5 h. Brains were taken before (using a mildly IMB diet)
      or after (using moderately or severely IMB diet) food intake was significantly (P
      < 0.05) depressed. Brain areas were dissected and analyzed for monoamines,
      metabolites and amino acids. Only in the anterior piriform cortex (APC), a brain
      area that may contain the amino acid chemosensor, was the limiting amino acid
      lower in IMB groups than in controls across all of the experiments. Before the
      onset of the anorectic response to the IMB diets, monoaminergic activity was
      affected in areas that have recognized monosynaptic connections with the APC. We
      propose a circuit for the neural responses in the initial recognition of acute
      amino acid deprivation that begins with activation of the APC and includes areas
      in the hindbrain and hypothalamus. After a significant hypophagic response,
      serotonergic indicators were altered in areas of the taste pathway and the limbic
      system. These results suggest that different circuits mediate the initial
      recognition and secondary conditioned responses to IMB diets.

PMID- 9521643
TI  - Cyclobutane thymine dimers with a disrupted phosphodiester bond are refractory to
      T4 endonuclease V digestion but have increased sensitivity to UvrABC nuclease.
AB  - UV irradiation induces the dimerization of synthetic single-stranded, 80-mer
      oligonucleotides with self-complementary, alternating purine-pyrimidine
      sequences, and terminal 5'- and 3'-thymines; this process can be reversed by
      photoreactivation. The UV-induced 160-mers are sensitive to digestion by the
      restriction enzyme SnaBI, but monomers are insensitive to digestion, indicating
      that UV irradiation stabilizes the formation of double-stranded DNA. These
      results suggest that UV irradiation of these 80-mer oligonucleotide substrates
      induces the formation of a novel cyclobutane thymine dimer which lacks an
      intradimer phosphodiester bond (CPD*). This CPD*, linking the terminal thymines
      of two separate 80-mer molecules, is formed in a double-stranded DNA region
      created by self-annealing and intermolecular hybridization of the two 80-mer
      strands. We have found that these UV-induced CPD* in 160-mers are sensitive to
      cleavage by the nucleotide excision enzyme complex UvrABC nuclease, but resistant
      to cleavage by the cyclobutane pyrimidine dimer-specific enzyme T4 endonuclease
      V. However, pretreatment of the 160-mers with ligase reverses their sensitivity
      to these two enzymes, significantly reducing their susceptibility to cleavage by
      UvrABC nuclease but dramatically increasing their susceptibility to cleavage by
      T4 endonuclease. The biological significance of these findings is discussed.

PMID- 9521644
TI  - Bovine epidermal fatty acid-binding protein: determination of ligand specificity
      and cellular localization in retina and testis.
AB  - The fatty acid-binding protein (FABP) family consists of small, cytosolic
      proteins believed to be involved in the uptake, transport, and solubilization of
      their hydrophobic ligands. Members of this family have highly conserved sequences
      and tertiary structures. Using an antibody against testis lipid-binding protein,
      a member of the FABP family, a protein was identified from bovine retina and
      testis that coeluted with exogenously added docosahexaenoic acid during
      purification. Amino acid sequencing and subsequent isolation of its cDNA revealed
      it to be nearly identical to a bovine protein expressed in the differentiating
      lens and to be the likely bovine homologue of the human epidermal fatty acid
      binding protein (E-FABP). From quantitative Western blot analysis, it was
      estimated that bovine E-FABP comprised 0.9%, 0.1%, and 2.4% of retina, testis,
      and lens cytosolic proteins, respectively. Binding studies using the fluorescent
      probe ADIFAB indicated that this protein bound fatty acids of differing levels of
      saturation with relatively high affinities. Kd values ranged from 27 to 97 nM. In
      addition, the protein was immunolocalized to the Muller cells in the retina as
      well as to Sertoli cells in the testis. The location of bovine E-FABP in cells
      known to be supportive to other cell types in their tissues and the ability of E
      FABP to bind a variety of fatty acids with similar affinities indicate that it
      may be involved in the uptake and transport of fatty acids essential for the
      nourishment of the surrounding cell types.

PMID- 9521645
TI  - Structure and ligand binding determinants of the recombinant kringle 5 domain of
      human plasminogen.
AB  - The X-ray crystal structure of the recombinant (r) kringle 5 domain of human
      plasminogen (K5HPg) has been solved by molecular replacement methods using K1HPg
      as a model and refined at 1.7 A resolution to an R factor of 16.6%. The
      asymmetric unit of K5HPg is composed of two molecules related by a
      noncrystallographic 2-fold rotation axis approximately parallel to the z
      direction. The lysine binding site (LBS) is defined by the regions His33-Thr37,
      Pro54-Val58, Pro61-Tyr64, and Leu71-Tyr74 and is occupied in the apo-form by
      water molecules. A unique feature of the LBS of apo-K5HPg is the substitution by
      Leu71 for the basic amino acid, arginine, that in other kringle polypeptides
      forms the donor cationic center for the carboxylate group of omega-amino acid
      ligands. While wild-type (wt) r-K5HPg interacted weakly with these types of
      ligands, replacement by site-directed mutagenesis of Leu71 by arginine led to
      substantially increased affinity of the ligands for the LBS of K5HPg. As a
      result, binding of omega-amino acids to this mutant kringle (r-K5HPg[L71R]) was
      restored to levels displayed by the companion much stronger affinity HPg
      kringles, K1HPg and K4HPg. Correspondingly, alkylamine binding to r-K5HPg[L71R]
      was considerably attenuated from that shown by wtr-K5HPg. Thus, employing a
      rational design strategy based on the crystal structure of K5HPg, successful
      remodeling of the LBS has been accomplished, and has resulted in the conversion
      of a weak ligand binding kringle to one that possesses an affinity for omega
      amino acids that is similar to K1HPg and K4HPg.

PMID- 9521646
TI  - Conformational conversion of antithrombin to a fully activated substrate of
      factor Xa without need for heparin.
AB  - Regulation of the inhibitory activity of antithrombin, the principal inhibitor of
      the blood-clotting proteinases factor Xa and thrombin, is accomplished by binding
      to heparin. We report here an antithrombin variant in which serine at position
      380, 14 residues N-terminal from the reactive bond and at a hinge point in the
      structure, was replaced by cysteine to test a proposed mechanism of heparin
      activation of antithrombin as an inhibitor of factor Xa. By derivatization of
      this cysteine with a bulky group, fluorescein, the antithrombin became
      permanently and fully activated toward reaction with factor Xa in a manner
      analogous to heparin activation, albeit as a substrate. These findings establish
      a structural basis for the mechanism of heparin activation of antithrombin
      against factor Xa in agreement with that proposed from an X-ray structure of
      antithrombin.

PMID- 9521647
TI  - Substrate and inhibitor binding sites in Corynebacterium glutamicum
      diaminopimelate dehydrogenase.
AB  - The three-dimensional structures of Corynebacterium glutamicum diaminopimelate
      dehydrogenase as a binary complex with the substrate meso-diaminopimelate (meso
      DAP) and a ternary complex with NADP+ and an isoxazoline inhibitor [Abbot, S.D.,
      Lane-Bell, P., Kanwar, P.S.S., and Vederas, J. C. (1994) J. Am. Chem. Soc. 116,
      6513-6520] have been solved and refined against X-ray diffraction data to 2.2 A.
      Diaminopimelate dehydrogenase is a homodimer of approximately 35,000 molecular
      weight subunits and is the only dehydrogenase present in the bacterial
      diaminopimelate/lysine biosynthetic pathway. Inhibitors of the enzymes of L
      lysine biosynthesis have been proposed as potential antibiotics or herbicides,
      since mammals lack this metabolic pathway. Diaminopimelate dehydrogenase
      catalyzes the unique, reversible, pyridine dinucleotide-dependent oxidative
      deamination of the D-amino acid stereocenter of meso-diaminopimelate to generate
      L-2-amino-6-oxopimelate. The enzyme is absolutely specific for the meso
      stereoisomer of DAP and must distinguish between two opposite chiral amino acid
      centers on the same symmetric substrate. The determination of the three
      dimensional structure of the enzyme--meso-diaminopimelate complex allows a
      description of the molecular basis of this stereospecific discrimination. The
      substrate is bound in an elongated cavity, in which the distribution of residues
      that act as hydrogen bond donors or acceptors defines a single orientation in
      which the substrate may bind in order to position the D-amino acid center of meso
      DAP near the oxidized nucleotide. The previously described isoxazoline inhibitor
      binds at the same site as DAP but has its L-amino acid center positioned where
      the D-amino acid center of meso-DAP would normally be located, thereby generating
      a nonproductive inhibitor complex. The relative positions of the N-terminal
      dinucleotide and C-terminal substrate-binding domains in the diaminopimelate
      dehydrogenase--NADP+, diaminopimelate dehydrogenase--DAP, and diaminopimelate
      dehydrogenase--NADP(+)--inhibitor complexes confirm our previous observations
      that the enzyme undergoes significant conformational changes upon binding of both
      dinucleotide and substrate.

PMID- 9521648
TI  - Role of the omega-loop in the activity, substrate specificity, and structure of
      class A beta-lactamase.
AB  - The structure of class A beta-lactamases contains an omega-loop associated with
      the active site, which carries a key catalytic residue, Glu166. A 16-residue
      omega-loop deletion mutant of beta-lactamase from Staphylococcus aureus PC1,
      encompassing residues 163-178, was produced in order to examine the functional
      and structural role of the loop. The crystal structure was determined and refined
      at 2.3 A, and the kinetics of the mutant enzyme was characterized with a variety
      of beta-lactam antibiotics. In general, the wild-type beta-lactamase hydrolyzes
      penicillin compounds better than cephalosporins. In contrast, the deletion of the
      omega-loop led to a variant enzyme that acts only on cephalosporins, including
      third generation compounds. Kinetic measurements and electrospray mass
      spectrometry revealed that the first and third generation cephalosporins form
      stable acyl-enzyme complexes, except for the chromogenic cephalosporin,
      nitrocefin, which after acylating the enzyme undergoes hydrolysis at a 1000-fold
      slower rate than that with wild-type beta-lactamase. Hydrolysis of the acyl
      enzyme adducts is prevented because the deletion of the omega-loop eliminates the
      deacylation apparatus comprising Glu166 and its associated nucleophilic water
      site. The crystal structure reveals that while the overall fold of the mutant
      enzyme is similar to that of the native beta-lactamase, local adjustments in the
      vicinity of the missing loop occurred. The altered beta-lactam specificity is
      attributed to these structural changes. In the native structure, the omega-loop
      restricts the conformation of a beta-strand at the edge of the active site
      depression. Removal of the loop provides the beta-strand with a new degree of
      conformational flexibility, such that it is displaced inward toward the active
      site space. Modeled Michaelis complexes with benzylpenicillin and cephaloridine
      show that the perturbed conformation of the beta-strand is inconsistent with
      penicillin binding because of steric clashes between the beta-lactam side chain
      substituent and the beta-strand. In contrast, no clashes occur upon cephalosporin
      binding. Recognition of third generation cephalosporins is possible because the
      bulky side chain substituents of the beta-lactam ring typical of these compounds
      can be accommodated in the space freed by the deletion of the omega-loop.

PMID- 9521649
TI  - Engineering an anion-binding cavity in antichymotrypsin modulates the "spring
      loaded" serpin-protease interaction.
AB  - Expressed in a kinetically trapped folding state, a serpin couples the
      thermodynamic driving force of a massive beta-sheet rearrangement to the
      inhibition of a target protease. Hence, the serpin-protease interaction is the
      premier example of a "spring-loaded" protein-protein interaction. Amino acid
      substitutions in the hinge region of a serpin reactive loop can weaken the
      molecular spring, which converts the serpin from an inhibitor into a substrate.
      To probe the molecular basis of this conversion, we report the crystal structure
      of A349R antichymotrypsin in the reactive loop cleaved state at 2.1 A resolution.
      This amino acid substitution does not block the beta-sheet rearrangement despite
      the burial of R349 in the hydrophobic core of the cleaved serpin along with a
      salt-linked acetate ion. The inhibitory activity of this serpin variant is not
      obliterated; remarkably, its inhibitory properties are anion-dependent due to the
      creation of an anion-binding cavity in the cleaved serpin.

PMID- 9521651
TI  - Conformation and DNA binding properties of a single-stranded DNA binding region
      of sigma 70 subunit from Escherichia coli RNA polymerase are modulated by an
      interaction with the core enzyme.
AB  - A derivative of the sigma 70 subunit from Escherichia coli RNA polymerase with
      specific fluorescence probes in conserved region 2.3 (DNA "melting motif") was
      prepared by replacing tryptophan residues at positions 314 and 326 of the wild
      type sigma 70 with alanine. The remaining two tryptophan residues (Trp 433 and
      434) of [Ala 314, 326]sigma 70 were biosynthetically replaced with 5-hydroxy
      tryptophan (5OHTrp), a fluorescent tryptophan analogue with unique emission that
      can be selectively observed both in free 5OHTrp[Ala 314, 326]sigma 70 as well as
      in 5OHTrp[Ala 314, 326]sigma 70 bound to the core RNA polymerase. Fluorescence
      quenching experiments revealed that positions 433 and 434 were solvent exposed in
      free 5OHTrp[Ala314, 326]sigma 70. The binding of sigma 70 to core polymerase
      reduced the solvent exposure of these residues. In the presence of single
      stranded oligonucleotides, fluorescence of 5OHTrp at position 433 and 434 was
      quenched approximately 65% and these residues became inaccessible to the solvent.
      Using fluorescence of 5OHTrp at positions 433 and 434 as a specific signal of DNA
      binding, we show that free sigma 70 bound single-stranded DNA weakly and did not
      discriminate between nontemplate and template strand of promoter DNA. Binding of
      sigma 70 to the core increased the affinity for binding nontemplate DNA, whereas
      the affinity to template or "nonspecific" DNA was reduced, resulting in a
      holoenzyme which could bind nontemplate strand approximately 200-fold better then
      the template strand. We concluded that Trp 433 and 434 of sigma 70 are located
      within a single-stranded DNA binding region of sigma 70 and that binding of sigma
      70 to the core enzyme induced conformational changes in a single-stranded DNA
      binding region of the protein. As a consequence of these conformational changes,
      sigma 70 subunit gains the specificity for the nontemplate strand of the melted
      region in the "open" complex.

PMID- 9521650
TI  - Proton transfer in benzyl alcohol dehydrogenase during catalysis: alternate
      proton-relay routes.
AB  - His51 in horse liver alcohol dehydrogenase (ADHE) has been proposed to act as a
      proton donor/acceptor in the NAD+/NADH-dependent oxidation/reduction of
      alcohol/aldehyde. The residue corresponding to His51 of ADHE is Val51 (Val45 in
      the protein sequence) in benzyl alcohol dehydrogenase (BADH) encoded by TOL
      plasmid pWW0. The 3-D structure of BADH modeled from the crystal structure of
      ADHE suggests that His47 (His41 in the protein sequence, corresponding to Arg47
      in ADHE) of BADH would play the role of His51 in ADHE. To test this hypothesis,
      mutants of BADH, in which His47 was replaced by Gln(His47Gln) and/or Val51 was
      replaced by His (Val51His), were constructed. The kcat/K(m) value of the His47Gln
      mutant for benzyl alcohol was 125-fold lower than that of wild-type BADH, while
      the kcat/K(m) value of the His47Gln/Val51His double mutant was 12-fold higher
      than that of the His47Gln mutant. The kcat/K(m) value of the His47Gln mutant
      increased with increasing concentration of exogenous amines. These results
      suggest that His47 in wild-type BADH, exogenous amines in the His47Gln mutant,
      and His51 in the double mutant act as a general base catalyst during alcohol
      oxidation.

PMID- 9521652
TI  - Transient high affinity binding of tissue factor pathway inhibitor-factor Xa
      complexes to negatively charged phospholipid membranes.
AB  - The interaction of tissue factor pathway inhibitor (TFPI), factor Xa, and TFPI
      factor Xa complexes with negatively charged phospholipid membranes composed of 25
      mol % phosphatidylserine and 75 mol % phosphatidylcholine was studied by
      ellipsometry. The binding of TFPI alone was negligible; factor Xa bound with
      moderate affinity, with a dissociation constant Kd = 42 nM. Formation of the TFPI
      factor Xa complex drastically enhanced the affinity for phospholipid membranes,
      Kd = 5 nM, compared to that of either protein alone. TFPI1-161, a TFPI variant
      lacking the third Kunitz domain and the positively charged C-terminus did not
      enhance binding affinity of the factor Xa. Analysis of the kinetics of adsorption
      and desorption confirmed the equilibrium binding data, although upon longer
      residence at the lipid membrane the desorption rate of TFPI-factor Xa complexes
      became slower, indicating an increase in affinity with longer residence of the
      TFPI-factor Xa complexes at the membrane. In contrast, binding of TFPI-factor Xa
      complexes in the presence of an excess factor Xa was transient; maximal binding
      is followed by a slow desorption of the complex. Immunoblot analysis revealed
      that this desorption was accompanied with cleavage of TFPI by membrane-bound
      factor Xa. Collectively, our results show that phosphatidylserine containing
      membranes will accumulate tightly bound TFPI-factor Xa complexes, and that
      uncomplexed, phospholipid-bound, factor Xa, will cause limited proteolysis of
      TFPI accompanied by simultaneous release of these complexes from the phospholipid
      membrane.

PMID- 9521653
TI  - Spin-lattice relaxation of the phyllosemiquinone radical of photosystem I.
AB  - The spin-lattice relaxation time (T1) of the phyllosemiquinone anion radical, A1
      , of the photosystem I (PSI) reaction center, were measured between 4.5 and 85 K
      by electron spin-echo spectroscopy. The selective removal of the iron-sulfur
      centers, FA, FB, and FX, from PSI allowed the measurement of the intrinsic T1 of
      the A1- radical. The temperature dependence of the intrinsic (T1)-1 for A1- was
      found to be approximately T1.3 +/- 0.1. The spin-lattice relaxation of the
      reduced form of iron-sulfur center FX was also measured at low temperatures, in
      FA/FB-depleted PSI membranes. It was found that the fast-relaxing FX center
      enhances the spin-lattice relaxation of the phyllosemiquinone due to dipolar
      coupling. The effect of the reduced forms of FA/FB on the T1 of the
      phyllosemiquinone was minor compared to the effect of FX. By analyzing the data
      with a dipolar model in the light of limitations imposed by other information
      present in the literature, the distance between the phyllosemiquinone and FX in
      PSI is estimated to be 14.8 +/- 4 A.

PMID- 9521654
TI  - Mutational analysis of the P-glycoprotein first intracellular loop and flanking
      transmembrane domains.
AB  - The role of individual intracellular (IC) loops linking transmembrane (TM)
      domains in P-glycoprotein (P-gp) function remains largely unknown. The high
      degree of sequence conservation of these regions in the P-gp family and other ABC
      transporters suggests an important role in a common mechanism of action of these
      proteins. To gain insight into this problem, we have randomly mutagenized a
      portion of TM2, the entire IC1 loop, TM3, the entire extracellular loop (EC2),
      and part of TM4, and analyzed the effect of such mutations on P-gp function.
      Random mutagenesis was carried out using Taq DNA polymerase and dITP under
      conditions of low polymerase fidelity, and the mutagenized segments were
      reintroduced in the full length mdr3 cDNA by homologous recombination in the
      yeast Saccharomyces cerevisiae strain JPY201. The biological activity of mutant P
      gp variants was analyzed in yeast by their ability to confer cellular resistance
      to the antifungal drug FK506 and the peptide ionophore valinomycin, and by their
      ability to complement the yeast Ste6 gene and restore mating in a yeast strain
      bearing a null mutation [Raymond, M., et al. (1992) Science 256, 232-4] at this
      locus. The analysis of 782 independent yeast transformants allowed the
      identification of 49 independent mutants bearing single amino acid substitutions
      in the mutagenized segment resulting in an altered P-gp function. The mutants
      could be phenotypically classified into two major groups, those that resulted in
      partial or complete overall loss of function and those that seemed to affect
      substrate specificity. Several of the mutants affecting overall activity mapped
      in IC1; in particular we identified a segment of four consecutive mutation
      sensitive residues (TRLT, positions 169-172) with such a phenotype. On the other
      hand, we identified a cluster of mutants affecting substrate specificity within
      the short EC2 segment and in the adjacent portion of the neighboring TM4 domain.
      Expression and partial purification of a representative subset of these mutants
      showed that in all but two cases, loss of function was associated with loss of
      drug-induced ATPase activity of P-gp. Therefore, it appears that TM domains, IC
      and EC loops, are structurally and functionally tightly coupled in the process of
      drug stimulatable ATPase characteristic of P-gp.

PMID- 9521655
TI  - A high-affinity inhibitor of yeast carboxypeptidase Y is encoded by TFS1 and
      shows homology to a family of lipid binding proteins.
AB  - A 25-kDa inhibitor of the vacuolar enzyme carboxypeptidase Y from Saccharomyces
      cerevisiae has been characterized. The inhibitor, Ic, binds tightly with an
      apparent Ki of 0.1 nM. Consistent with a cytoplasmic localization, Ic is soluble
      and contains no sequences which could serve as potential signals for transport
      into the endoplasmic reticulum. Surprisingly, Ic is encoded by TFS1, which has
      previously been isolated as a high-copy suppressor of cdc25-1. CDC25 encodes the
      putative GTP exchange factor for Ras1p/Ras2p in yeast. In an attempt to
      rationalize this finding, we looked for a physiological relationship by deleting
      or overexpressing the gene for carboxypeptidase Y in a cdc25-1 strain. However,
      this did not change the phenotype of this mutant strain. Ic is the first member
      of a new family of protease inhibitors. The inhibitor is not hydrolyzed on
      binding to CPY. It has fairly high degree of specificity, showing a 200-fold
      higher Ki toward a carboxypeptidase from Candida albicans which is highly
      homologous to carboxypeptidase Y. The TFS1 gene product shows extensive
      similarity to a class of proteins termed "21-23-kDa lipid binding proteins",
      members of which are found in several higher eukaryotes, including man. These
      proteins are highly abundant in some tissues (e.g., brain) and have in general
      been found to bind lipids. Considering their homology to Ic, it is tempting to
      speculate that they may also be inhibitors of serine carboxypeptidases.

PMID- 9521656
TI  - Substrate specificity of deubiquitinating enzymes: ubiquitin C-terminal
      hydrolases.
AB  - Ubiquitin C-terminal hydrolases (UCH) are deubiquitinating enzymes which
      hydrolyze C-terminal esters and amides of ubiquitin. Here we report the
      processing of a number of ubiquitin derivatives by two human UCH isozymes
      (isozymes L1 and L3) and find that these enzymes show little discrimination based
      on the P1' amino acid, except that proline is cleaved slowly. Ubiquitinyllysine
      derivatives linked by the alpha- or epsilon-amino group are hydrolyzed at
      identical rates. Isozyme-specific hydrolytic preferences are only evident when
      the leaving group is large. The ubiquitin gene products can be cotranslationally
      processed by one or both of these UCH isozymes, and purified UbCEP52 can be
      hydrolyzed by UCH isozyme L3. Binding of nucleic acid by UbCEP52 converts it to a
      form resistant to processing by these enzymes, apparently because of the
      formation of a larger, more tightly folded substrate. Consistent with this
      postulate is the observation that these enzymes do not hydrolyze large ubiquitin
      derivatives such as N epsilon-ubiquitinyl-cytochrome-c, N epsilon
      K48polyubiquitinyl-lysozyme, or an N alpha-ubiquitinyl-beta-galactosidase fusion
      protein. Thus, these enzymes rapidly and preferentially cleave small leaving
      groups such as amino acids and oligopeptides from the C-terminus of ubiquitin,
      but not larger leaving groups such as proteins. These data suggest that the
      physiological role of UCH is to hydrolyze small adducts of ubiquitin and to
      generate free monomeric ubiquitin from ubiquitin proproteins, but not to
      deubiquitinate ubiquitin-protein conjugates or disassemble polyubiquitin chains.

PMID- 9521657
TI  - Kinetic role of electrostatic interactions in the unfolding of hyperthermophilic
      and mesophilic rubredoxins.
AB  - The temperature dependence of the unfolding kinetics of rubredoxins from the
      hyperthermophile Pyrococcus furiosus (RdPf) and the mesophile Clostridium
      pasteurianum (RdCp) has been studied. Results show that RdPf unfolds much more
      slowly, under all experimentally accessible temperature regimes, than RdCp and
      other typical mesophilic proteins. Rates of RdCp and RdPf unfolding decrease upon
      increasing the pH above 2 and diverge dramatically at pH 7. As shown by detailed
      electrostatic energy calculations, this is the result of a differential degree of
      protonation of the negatively charged amino acids, which causes distinct
      electrostatic configurations as a function of pH. We propose that ion pairs,
      particularly those that are placed in key surface positions, may play a kinetic
      role by mildly clamping the protein and thereby influencing the nature and the
      number of the vibrational normal modes that are thermally accessible upon
      unfolding. More generally, these modes are also likely to be affected by the
      favorable electrostatic configurations, which we have shown to be directly linked
      to the extremely slow unfolding rates of RdPf at neutral pH. Even at pH 2, in the
      absence of any salt bridges, the unfolding rates of RdPf are much smaller than
      those of RdCp. This is ascribed to presently unidentified structural elements of
      nonelectrostatic nature. Since electrostatic effects influence the unfolding
      kinetics of both mesophilic and thermophilic rubredoxins, these findings may be
      of general significance for proteins.

PMID- 9521658
TI  - Unfolding mechanism of rubredoxin from Pyrococcus furiosus.
AB  - As part of our studies on the structural and dynamic properties of
      hyperthermostable proteins, we have investigated the unfolding pathways of the
      small iron-sulfur protein rubredoxin from Pyrococcus furiosus (RdPf) at pH 2.
      Unfolding has been initiated by temperature jump, triggered by manual mixing of a
      concentrated protein solution into a thermally preequilibrated buffer. The
      process has been followed in real time by absorption, tryptophan fluorescence
      emission, and far-UV circular dichroism. Unlike the case of the mesophilic
      rubredoxin from Clostridium pasteurianum (RdCp), RdPf displays a complex
      unfolding kinetics, pointing to the formation of at least three intermediates.
      All of the steps, including the one involving metal ion release, are extremely
      slow. However, hydrophobic core relaxation--not Fe3+ loss--is rate-determining
      for RdPf unfolding. This clearly rules out the fact that Fe3+ is solely
      responsible for the kinetic stability of RdPf. Results have been discussed in
      terms of sequential vs parallel pathways, and the possible role of irreversible
      phenomena has been taken into consideration. Aggregation does not appear to play
      a significant role in the observed kinetic complexities. According to a proposed
      sequential mechanism, partial release of secondary structure elements precedes
      iron loss, which is then followed by further loss of beta-sheet content and,
      finally, by hydrophobic relaxation. Although the main features of the RdPf
      unfolding mechanism remain substantially unchanged over the experimentally
      accessible temperature range, final hydrophobic relaxation gets faster, relative
      to the other events, as the temperature is decreased. A qualitative assessment of
      the unfolding activation parameters suggests that this arises from the very low
      activation energies (Ea) that characterize this step.

PMID- 9521659
TI  - Interplay between S1 and S4 subsites in Kex2 protease: Kex2 exhibits dual
      specificity for the P4 side chain.
AB  - The yeast Kex2 protease is the prototype of a family of eukaryotic proprotein
      processing proteases that includes PC1, PC2, and furin. The catalytic domains of
      these enzymes are homologous to the degradative serine proteases of the
      subtilisin family. Kex2 exhibits optimal activity toward substrates with Lys or
      Arg at P2 and Arg at P1 (Lys-Arg or Arg-Arg cleavage sites). However, mammalian
      proprotein processing proteases such as furin exhibit more stringent requirements
      for basic residues at P4 than at P2. Here we demonstrate that Kex2 protease also
      recognizes P4, with dual specificity for aliphatic and basic residues.
      Recognition of P4 is even more readily apparent in substrates having a poor P1
      residue (Lys). Kinetic analysis of a series of otherwise identical fluorogenic
      substrates with Lys at P1 and different residues at P4 indicates that large,
      aliphatic P4 residues increase kcat/KM by 100-fold. However, smaller residues or
      acidic residues at P4 do not. P4 Arg also confers efficient cleavage on such a
      substrate, but the uncharged isostere of Arg, citrulline, does not. Kex2 may thus
      possess distinct subsites that recognize aliphatic or basic P4 side chains.
      Although a favorable P4 residue can partially compensate for the defects in kcat
      and kcat/KM seen with Lys in place of Arg at P1, this substitution resulted in a
      change in rate-determining step for all substrates examined. As previously seen
      in the case of subtilisin, effects of substitutions at the P1 and P4 positions
      were not independent, suggesting that interplay between these two positions is a
      common feature of substrate specificity for both processing proteases and
      degradative enzymes of the subtilisin superfamily.

PMID- 9521660
TI  - Serine protease of hepatitis C virus expressed in insect cells as the NS3/4A
      complex.
AB  - Hepatitis C virus (HCV) protease NS3 and its protein activator NS4A participate
      in the processing of the viral polyprotein into its constituent nonstructural
      proteins. The NS3/4A complex is thus an attractive target for antiviral therapy
      against HCV. We expressed the full-length NS3 and NS4A in insect cells as a
      soluble fusion protein with an N-terminal polyhistidine tag and purified the two
      proteins to homogeneity. Cleavage at the junction between HisNS3 and NS4A occurs
      during expression, producing a noncovalent complex between HisNS3 and NS4A with a
      subnanomolar dissociation constant. We purified the HisNS3/4A complex by
      detergent extraction of cell lysate and by metal chelate chromatography. We
      removed the His tag by thrombin cleavage and then further purified the complex by
      gel filtration. The purified NS3/4A complex is active in a protease assay using a
      synthetic peptide substrate derived from the NS5A-NS5B junction, with kcat/K(m)
      of 3700 (+/- 600) M-1 s-1, an order of magnitude above those previously reported
      for NS3 expressed by other strategies. This high protease activity implies that
      the full-length sequences of NS3 and NS4A are required for optimal activity of
      the NS3 protease domain. We examined the dependence of the NS3/4A protease
      activity on buffer conditions, temperature, and the presence of detergents. We
      find that, under most conditions, NS3 protease activity is dependent on the
      aggregation state of the NS3/4A complex. The monodisperse, soluble form of the
      NS3/4A complex is associated with the highest protease activity.

PMID- 9521661
TI  - Structure and position of the N-terminal membrane-binding domain of pp60src at
      the membrane interface.
AB  - Hydrophobic and electrostatic interactions between the acylated N-terminal end of
      Src and lipid bilayers are responsible for the attachment of this nonreceptor
      tyrosine kinase to the membrane-solution interface. To investigate the structure
      and dynamics of this domain at the membrane interface, a series of peptides based
      upon the N-terminal end of pp60src, myr-src(2-16), was synthesized with single
      site cysteine substitutions and derivatized with a sulfhydryl-reactive proxyl
      nitroxide. The EPR line shapes and mobility of these peptides when bound to the
      membrane interface were consistent with an extended peptide conformation, and no
      evidence was found for either a helical or sheet structure. Line shapes on the
      myristoylated N-terminal end indicate that this segment is more restricted in its
      motion than at the C-terminus. Although the membrane affinity of this peptide is
      much stronger in the presence of acidic lipid, EPR line shapes were not strongly
      affected by the presence of acidic lipid. An EPR power saturation technique was
      used to provide information on the position of nitroxides from the interface for
      the membrane-bound peptide. When membrane bound, labeled side chains at the N
      terminal end of the peptide were found to lie in the aqueous phase near the
      membrane interface; however, for the C-terminal half of the peptide, residues
      were further off the membrane and were 10-15 A from the interface. Peptides
      derived from the membrane and calmodulin binding domains of the myristoylated
      alanine-rich C kinase substrate and neuromodulin were previously found to be in
      extended conformations; however, side chains for these peptides penetrated the
      membrane-solution interface. We speculate that the relatively polar character of
      the N-terminal segment of Src and a Born repulsion energy prevent this peptide
      from penetrating into the membrane interface when membrane bound.

PMID- 9521662
TI  - Reconstitution of core light-harvesting complexes of photosynthetic bacteria
      using chemically synthesized polypeptides. 1. Minimal requirements for subunit
      formation.
AB  - Described are the chemical synthesis, isolation and characterization of each of
      three polypeptides whose amino acid sequences reproduce portions of the amino
      acid sequence of the beta-polypeptides of the core light-harvesting complex (LH1)
      of Rhodobacter sphaeroides or Rhodospirillum rubrum. The native beta-polypeptides
      of LH1 of these organisms contain 48 and 54 amino acids, respectively. The
      smallest synthetic polypeptide had an amino acid sequence identical to that of
      the last 16 amino acids of the beta-polypeptide of Rb. sphaeroides (sph beta 16)
      but failed to form either a subunit- or LH1-type complex under reconstitution
      conditions. Also, this polypeptide, lengthened on the N terminus by adding the
      sequence Lys-Ile-Ser-Lys to enhance solubility, failed to form a subunit- or LH1
      type complex. In contrast, polypeptides containing either the 31 amino acids at
      the C terminus of the beta-polypeptide of Rb. sphaeroides (sph beta 31) or the
      equivalent 31 amino acids of the beta-polypeptide of Rs. rubrum (rr beta 31) were
      fully competent in forming a subunit-type complex and exhibited association
      constants for complex formation comparable to or exceeding those of the native
      beta-polypeptides. The absorption and CD spectra of these subunit-type complexes
      were nearly identical to those of subunit complexes formed with native beta
      polypeptides. It may be concluded that all structural features required to make
      the subunit complex are present in the well-defined, chemically synthesized
      polypeptides. Neither polypeptide appeared to interact with the native alpha
      polypeptides to form a LH1-type complex. However, sph beta 31 formed a LH1-type
      complex absorbing at 849 nm without an alpha-polypeptide. Although chemical
      syntheses of polypeptides of this size are common, the purification of membrane
      spanning segments is much more challenging because the polypeptides lack
      solubility in water. The chemical syntheses reported here represent the first
      such syntheses of membrane-spanning polypeptides which display native activity
      upon reconstitution.

PMID- 9521663
TI  - Reconstitution of core light-harvesting complexes of photosynthetic bacteria
      using chemically synthesized polypeptides. 2. Determination of structural
      features that stabilize complex formation and their implications for the
      structure of the subunit complex.
AB  - Chemically synthesized polypeptides have been utilized with a reconstitution
      assay to determine the role of specific amino acid side chains in stabilizing the
      core light-harvesting complex (LH1) of photosynthetic bacteria and its subunit
      complex. In the preceding paper [Meadows, K. A., Parkes-Loach, P. S., Kehoe, J.
      W., and Loach, P. A. (1998) Biochemistry 37, 3411-3417], it was demonstrated that
      31-residue polypeptides (compared to 48 and 54 amino acids in the native
      polypeptides) having the same sequence as the core region of the beta-polypeptide
      of Rhodobacter sphaeroides (sph beta 31) or Rhodospirillum rubrum (rr beta 31)
      could form subunit-type complexes. However, neither polypeptide interacted with
      the native alpha-polypeptides to form a native LH1 complex. In this paper, it is
      demonstrated that larger segments of the native Rb. sphaeroides beta-polypeptide
      possess native behavior in LH1 formation. Polypeptides were synthesized that were
      six (sph beta 37) and ten amino acids (sph beta 41) longer than sph beta 31.
      Although sph beta 37 exhibited behavior nearly identical to that of sph beta 31,
      sph beta 41 behaved more like the native polypeptide. In the case of rr beta 31,
      a polypeptide with four additional amino acids toward the C terminus was
      synthesized (rr beta 35). Because LH1-forming behavior was not recovered with
      this longer polypeptide, one or more of the three remaining amino acids at the C
      terminal end of the native beta-polypeptide seem to play an important role in LH1
      stabilization in Rs. rubrum. Three analogues of the core region of the Rb.
      sphaeroides beta-polypeptide were synthesized, in each of which one highly
      conserved amino acid was changed. Evidence was obtained that the penultimate
      amino acid, a Trp residue, is especially important for subunit formation. When it
      was changed to Phe, the lambda Max of the subunit shifted from 823 to 811 nm and
      the association constant decreased about 500-fold. Changing each of two other
      amino acids had smaller effects on subunit formation. Changing Trp to Phe at the
      location six amino acid residues toward the C terminus from the His coordinated
      to Bchl resulted in an approximately 10-fold decrease in the association constant
      for subunit formation but did not affect the formation of a LH1-type complex
      compared to sph beta 31. Finally, changing Arg to Leu at the location seven amino
      acid residues toward the C terminus from the His coordinated to Bchl decreased
      the association constant for subunit formation by about 30-fold. In this case, no
      LH1-type complex could be formed. On the basis of these results, in comparison
      with the crystal structure of the LH2 beta-polypeptide of Rhodospirillum
      molischianum, two possible structures for the subunit complex are suggested.

PMID- 9521664
TI  - Electron transfer in photosystem I reaction centers follows a linear pathway in
      which iron-sulfur cluster FB is the immediate electron donor to soluble
      ferredoxin.
AB  - Reaction centers of photosystem I contain three different [4Fe-4S] clusters named
      FX, FA, and FB. The terminal photosystem I acceptors (FA, FB) are distributed
      asymmetrically along the membrane normal, with one of them (FA or FB) being
      reduced from FX and the other one (FB or FA) reducing soluble ferredoxin. In the
      present work, kinetics of electron transfer has been measured in PSI from the
      cyanobacterium Synechocystis sp. PCC 6803 after inactivation of FB by treatment
      with HgCl2. Photovoltage measurements indicate that, in the absence of FB,
      reduction of FA by FX is still faster than the rate of FX reduction [(210 ns)-1].
      Flash-absorption measurements show that the affinity of ferredoxin for HgCl2
      treated PSI is only decreased by a factor of 3-4 compared to untreated
      photosystem I. The first-order rate of ferredoxin reduction by FA-, within the
      photosystem I/ferredoxin complex, has been calculated from measurements of P700+
      decay. Compared to control PSI, this rate is several orders of magnitude smaller
      (6 s-1 versus 10(4)-10(6) s-1). Moreover, it is smaller than the rate of
      recombination from FA-, resulting in inefficient ferredoxin reduction (yield of
      25%). After reconstitution of FB, about half of the reconstituted photosystem I
      reaction centers recover fast reduction of ferredoxin with kinetics similar to
      that of untreated photosystem I. These results support FB as the direct partner
      of ferredoxin and as the more distal cluster of photosystem I with respect to the
      thylakoid membrane, in accordance with a linear electron-transfer pathway FX-->FA
      ->FB-->ferredoxin.

PMID- 9521665
TI  - Probing intramolecular electron transfer within flavocytochrome b2 with a
      monoclonal antibody.
AB  - Flavocytochrome b2 or L-lactate dehydrogenase from yeast is a tetrameric enzyme
      which oxidizes lactate at the expense of cytochrome c or artificial electron
      acceptors. The prosthetic group FMN is reduced by the substrate and then
      transfers sequentially the reducing equivalents to heme b2 in the same subunit.
      The latter is reoxidized by cytochrome c. The crystal structure of the enzyme
      indicates that each subunit is composed of a flavodehydrogenase domain (FDH) and
      a cytochrome b2 domain; the latter, which encompasses the first 99 residues of
      the peptide chain, is mobile relative to the tetrameric FDH assembly. We describe
      here the properties of a monoclonal antibody elicited against the holoenzyme. It
      only recognizes the heme-binding domain, with a Kd lower than 10(-7) M, and its
      epitope is conformational. In the enzyme-IgG complex, flavin is reduced normally
      and can be reoxidized by ferricyanide, but no longer by heme b2. Stopped-flow
      experiments in the absence of electron acceptors give no indication of flavin to
      heme electron transfer in the enzyme-antibody complex. In other words, the two
      domains are functionally uncoupled. The binding stoichiometry is 1/1 for the Fab
      fragment with respect to the isolated, monomeric, heme-binding domain, but 2/4
      with respect to the enzyme tetramer; furthermore, binding of two Fab fragments
      per tetramer is sufficient to cause inhibition of intra-subunit flavin to heme
      electron transfer in all four subunits. Altogether these results can only be
      rationalized by considering that mobility of the cytochrome domain with respect
      to the FDH is an essential component of the catalytic cycle. The first experiment
      designed to locate the epitope shows it does not encompass the interdomain
      peptide linker (so-called hinge region, centered on residues 99-100).

PMID- 9521666
TI  - Effects of phosphatidylinositol diphosphate on phospholipid asymmetry in the
      human erythrocyte membrane.
AB  - While phospholipid asymmetry has been well characterized in red blood cells
      (RBCs), controversy exists as to what role PIP2 plays in cation-induced
      phosphatidylserine (PS) exposure. We report that PIP2 can redistribute
      intracellular cations and thereby lead to a loss of phospholipid asymmetry. Flow
      cytometry was employed to monitor intracellular cation levels by using the
      fluorophore Fluo-3 and exposure of PS on the outer surface of the RBC bilayer by
      using fluorescently labeled annexin V. The addition of PIP2 to RBCs led to a
      concentration-dependent increase in cytosolic cations and PS exposure. IF RBCs
      were preincubated with 25 microM neomycin sulfate, an inhibitor of
      phosphoinositide metabolism, PIP2-induced PS exposure decreased dramatically. If
      the RBC buffer system contained 2.5 mM EGTA, PS exposure also decreased
      significantly, suggesting a competition between intracellular Fluo-3 and
      extracellular EGTA. Together, these data indicate that (1) PS exposure was found
      in RBCs that exhibited an increased cytosolic cation concentration available for
      the fluorophore. Fluo-3, (2) both the level of intracellular cations and the
      movement of PS from the inner to the outer monolayer were affected by the level
      of PIP2 in the bilayer, (3) the cleavage of PIP2 by a phosphoinositide-specific
      phospholipase lead to the redistribution of intracellular cations and to an
      increase in the amount of PS exposed on the outer leaflet of the bilayer, and (4)
      a transient channel could be formed during the interaction of PIP2 with the RBC
      membrane which would then allow the transbilayer movement of phospholipids and
      cations.

PMID- 9521667
TI  - Substrate specificity of Staphylococcus hyicus lipase and Staphylococcus aureus
      lipase as studied by in vivo chimeragenesis.
AB  - Staphylococcus hyicus lipase (SHL) and Staphylococcus aureus lipase (SAL) are
      highly homologous enzymes, yet they show remarkable differences in their
      biochemical characteristics. SHL displays a high phospholipase activity,
      hydrolyses neutral lipids, and has no chain length preference, whereas SAL only
      degrades short-chain fatty acid esters. To identify the regions in the primary
      sequence of SHL responsible for phospholipase activity and chain length
      selectivity, a set of histidine-tagged SAL/SHL chimeras was generated by in vivo
      recombination in Escherichia coli. Several classes of chimeric enzymes were
      identified on the basis of restriction site analysis. All chimeras were well
      expressed as active enzymes. They were characterized for their specific
      activities on both phospholipids and p-nitrophenyl esters of various chain
      lengths. Phospholipase activity appeared to be determined by three regions, all
      located in the C-terminal domain of SHL. Testing of the enzymatic activity of the
      chimeras toward p-nitrophenyl esters showed that chain length selectivity is
      defined by elements within the region of residues 180-253. Moreover, also
      residues along the stretch 275-358 contribute to the binding of acyl chains.
      Interestingly, several chimeras were even more active than the parent enzymes on
      long-chain p-nitrophenyl esters.

PMID- 9521668
TI  - One-headed kinesin derivatives move by a nonprocessive, low-duty ratio mechanism
      unlike that of two-headed kinesin.
AB  - A single molecule of the "two-headed" motor enzyme kinesin can move along a
      microtubule continuously for many enzymatic turnovers (processive movement), and
      the velocity produced by one kinesin molecule is the same as that produced by
      many kinesin molecules (high duty ratio). We studied the microtubule movement
      driven at 1 mM ATP by biotinated N-terminal fragments of Drosophila kinesin heavy
      chain attached to streptavidin-coated coverslips at various surface densities.
      K448-BIO has velocity at a high density of vmax = 750 nm s-1 and is dimeric
      (hence two-headed); K365-BIO (vmax = 200 nm s-1) and K340-BIO (vmax = 90 nm s-1)
      are monomeric. Escape of microtubules from the surface was prevented by
      methylcellulose so that continuous trajectories of microtubules not continuously
      attached to motor molecules could be recorded by video microscopy. The component
      of instantaneous velocity parallel to the microtubule axis (v) was analyzed in
      trajectories with a mean velocity 0.4-0.7 times vmax. In K448-BIO trajectories,
      the distribution of v was bimodal with peaks near 0 and 750 nm s-1. Temporal
      autocorrelation analysis of v detected lengthy episodes of high-velocity movement
      consistent with isolated processive microtubule runs driven at vmax by single
      K448-BIO dimers. K365-BIO and K340-BIO trajectories had unimodal distributions of
      v and autocorrelation times much shorter than those for K448-BIO. Therefore the
      monomeric motors have duty ratio < 55% (i.e., no forward movement is generated
      for at least 45% of the enzymatic cycle time) or processivity below the detection
      limit of approximately 300 turnovers even in methylcellulose. Continuous movement
      at maximal velocity thus requires more than one kinesin head.

PMID- 9521669
TI  - Oligosaccharide binding characteristics of the molecular chaperones calnexin and
      calreticulin.
AB  - Calnexin and calreticulin are homologous molecular chaperones of the endoplasmic
      reticulum. Their binding to newly synthesized glycoproteins is mediated, at least
      in part, by a lectin site that recognizes the early N-linked oligosaccharide
      processing intermediate, Glc1Man9GlcNAc2. We compared the oligosaccharide binding
      specificities of calnexin and calreticulin in an effort to determine the basis
      for reported differences in their association with various glycoproteins. Using
      mono-, di-, and oligosaccharides to inhibit the binding of Glc1Man9GlcNAc2 to
      calreticulin and to a truncated, soluble form of calnexin, we show that the
      entire Glc alpha 1-3Man alpha 1-2Man alpha 1-2Man structure, extending from the
      alpha 1-3 branch point of the oligosaccharide core, is recognized by both
      proteins. Furthermore, analysis of the binding of monoglucosylated
      oligosaccharides containing progressively fewer mannose residues suggests that
      for both proteins the alpha 1-6 mannose branch point of the oligosaccharide core
      is also essential for recognition. Consistent with their essentially identical
      substrate specificities, calnexin and calreticulin exhibited the same relative
      affinities when competing for binding to the Glc1Man9GlcNAc2 oligosaccharide.
      Thus, differential glycoprotein binding cannot be attributed to differences in
      the lectin specificities or binding affinities of calnexin and calreticulin. We
      also examined the effects of ATP, calcium, and disulfide reduction on the lectin
      properties of calnexin and calreticulin. Whereas oligosaccharide binding was only
      slightly enhanced for both proteins in the presence of high concentrations of a
      number of adenosine nucleotides, removal of bound calcium abrogated
      oligosaccharide binding, an effect that was largely reversible upon readdition of
      calcium. Disulfide reduction had no effect on oligosaccharide binding by
      calnexin, but binding by calreticulin was inhibited by 70%. Finally, deletion
      mutagenesis of calnexin and calreticulin identified a central proline-rich region
      characterized by two tandem repeat motifs as a segment capable of binding
      oligosaccharide. This segment bears no sequence homology to the carbohydrate
      recognition domains of other lectins.

PMID- 9521671
TI  - Energetics of two-step binding of a chromophoric reaction product, trans-3
      indoleacryloyl-CoA, to medium-chain acyl-coenzyme-A dehydrogenase.
AB  - We previously demonstrated that the UV/visible spectrum of a chromophoric ligand,
      trans-3-indoleacryloyl-coenzyme-A (IACoA), is red-shifted (due to polarization of
      its carbonyl group) upon binding to pig kidney medium-chain acyl-CoA
      dehydrogenase (MCAD). The transient kinetic data revealed that the overall
      binding occurred in two steps. The first (fast) step involved the formation of an
      MCAD-IACoA collision complex in which the electronic structure of IACoA remained
      unchanged (the "colorless" complex), followed by a slow isomerization step with a
      concomitant red-shift in the IACoA spectrum (the "colored" complex) [Johnson, J.
      K., Wang, Z. X., and Srivastava, D. K. (1992) Biochemistry 31, 10564-10575]. To
      ascertain the energetics of the above two-step process, we investigated the
      temperature dependence of the spectral changes, binding constant of the MCAD
      IACoA complex, and the rate constants for the conversion between the colorless
      and colored complexes. The data revealed that as the temperature of the
      incubation mixture of MCAD and IACoA ([IACoA] >> [MCAD] > Kd) increases from 12
      to 35 degrees C, the resultant spectral peak of the MCAD-IACoA complex (lambda
      max = 417 nm) decreases. However, in this temperature range, the equilibrium
      constant for the second (isomerization) step remains unaffected. Isothermal
      titration calorimetric studies for the binding of IACoA to MCAD reveal that the
      overall binding energy at 25 degrees C (delta G degree = -7.4 kcal/mol) is
      contributed almost equally by the enthalpic (delta H degree = -3.7 kcal/mol) and
      entropic (T delta S degree = 3.7 kcal/mol) changes. As the temperature increases,
      both delta H degree and T delta S degree decrease proportionately, resulting in a
      strong enthalpy-entropy compensation effect. The temperature dependence of delta
      H degree yields a delta Cp degree value of -0.24 kcal/mol. The data presented
      herein throw light on the energetic consequences for the binding of IACoA to
      MCAD, the apparent similarity between the van't Hoff and calorimetric enthalpies,
      enthalpic and entropic contributions during the polarization of the carbonyl
      group of IACoA, and the overall structural-functional features of the enzyme
      ligand complex as well as enzyme catalysis.

PMID- 9521670
TI  - A single amino acid substitution in the human and a bacterial hypoxanthine
      phosphoribosyltransferase modulates specificity for the binding of guanine.
AB  - Early studies involving purine salvage in Salmonella typhimurium resulted in the
      isolation and identification of a mutant strain possessing a genetically modified
      hypoxanthine phosphoribosyl-transferase (HPRT) with enhanced substrate
      specificity for guanine [Benson, C. E., and Gots, J. S. (1975) J. Bacteriol. 121,
      77-82]. To explore the molecular basis for this altered substrate specificity in
      the mutant hpt gene product, degenerate oligonucleotide primers, designed
      according to the N- and C-termini of the HPRT of Escherichia coli, were used in
      polymerase chain reactions to amplify both the mutant and wild-type S.
      typhimurium hpt genes from genomic DNA. Analysis of the deduced amino acid
      sequences revealed that a single base mutation resulted in the encoding of a Thr
      in the mutant HPRT, instead of an Ile found in the wild-type enzyme, at a
      position analogous to position 192 (Leu-192) of the human HPRT. Comparison of
      kinetic data for purified recombinant mutant and wild-type HPRTs showed no
      difference in the overall catalytic efficiency (kcat/K(m)) with hypoxanthine as
      substrate, but with guanine, the mutant enzyme exhibited a more than 50-fold
      higher kcat/K(m) largely as a result of a decrease of nearly 2 orders of
      magnitude in K(m). Involvement in substrate binding of the cognate amino acid at
      position 192 in the human HPRT was investigated using site-directed mutagenesis.
      Mutation of Leu-192 to Thr did not significantly alter kcat/K(m) values for
      hypoxanthine and guanine compared to wild-type, and replacement of Leu-192 with
      Ile had no significant change in kinetics for either hypoxanthine or PRPP.
      However, this Ile substitution resulted in an over 15-fold decrease in the
      kcat/K(m) for guanine due to a greater than 15-fold increase in K(m). These
      results demonstrate that a single active site amino acid substitution in HPRTs
      can significantly alter the specificity for binding guanine.

PMID- 9521672
TI  - Aspartate-279 in aminolevulinate synthase affects enzyme catalysis through
      enhancing the function of the pyridoxal 5'-phosphate cofactor.
AB  - 5-Aminolevulinate synthase (ALAS) catalyzes the first step in the heme
      biosynthetic pathway in nonplant eukaryotes and some prokaryotes, which is the
      condensation of glycine with succinyl-coenzyme A to yield coenzyme A, carbon
      dioxide, and 5-aminolevulinate. ALAS requires pyridoxal 5'-phosphate as an
      essential cofactor and functions as a homodimer. D279 in murine erythroid enzyme
      was found to be conserved in all aminolevulinate synthases and appeared to be
      homologous to D222 in aspartate aminotransferase, where the side chain of the
      residue stabilizes the protonated form of the cofactor ring nitrogen, thus
      enhancing the electron sink function of the cofactor during enzyme catalysis.
      D279A mutation in ALAS resulted in no detectable enzymatic activity under
      standard assay conditions, and the conservative D279E mutation reduced the
      catalytic efficiency for succinyl-CoA 30-fold. The D279A mutation resulted in a
      19-fold increase in the dissociation constant for binding of the pyridoxal 5'
      phosphate cofactor. UV-visible and CD spectroscopic analyses indicated that the
      D279A mutant binds the cofactor in a different mode at the active site. In
      contrast to the wild-type and D279E mutant, the D279A mutant failed to catalyze
      the formation of a quinonoid intermediate upon binding of 5-aminolevulinate.
      Importantly, this partial reaction could be rescued in D279A by reconstitution of
      the mutant with the cofactor analogue N-methyl-PLP. The steady-state kinetic
      isotope effect when deuteroglycine was substituted for glycine was small for the
      wild-type enzyme (kH/kD = 1.2 +/- 0.1), but a strong isotope effect was observed
      with the D279E mutant (kH/kD = 7.7 +/- 0.3). pH titration of the external
      aldimine formed with ALA indicated the D279E mutation increased the apparent pKa
      for quinonoid formation from 8.10 to 8.25. The results are consistent with the
      proposal that D279 plays a crucial role in aminolevulinate synthase catalysis by
      enhancing the electron sink function of the cofactor.

PMID- 9521673
TI  - Selenium-containing formate dehydrogenase H from Escherichia coli: a
      molybdopterin enzyme that catalyzes formate oxidation without oxygen transfer.
AB  - Formate dehydrogenase H, FDH(Se), from Escherichia coli contains a molybdopterin
      guanine dinucleotide cofactor and a selenocysteine residue in the polypeptide.
      Oxidation of 13C-labeled formate in 18O-enriched water catalyzed by FDH(Se)
      produces 13CO2 gas that contains no 18O-label, establishing that the enzyme is
      not a member of the large class of Mo-pterin-containing oxotransferases which
      incorporate oxygen from water into product. An unusual Mo center of the active
      site is coordinated in the reduced Mo(IV) state in a square pyramidal geometry to
      the four equatorial dithiolene sulfur atoms from a pair of pterin cofactors and a
      Se atom of the selenocysteine-140 residue [Boyington, J. C., Gladyshev, V. N.,
      Khangulov, S. V., Stadtman, T. C., and Sun, P. D. (1997) Science 275, 1305-1308].
      EPR spectroscopy of the Mo(V) state indicates a square pyramidal geometry
      analogous to that of the Mo(IV) center. The strongest ligand field component is
      likely the single axial Se atom producing a ground orbital configuration Mo(dxy).
      The Mo-Se bond was estimated to be covalent to the extent of 17-27% of the
      unpaired electron spin density residing in the valence 4s and 4p selenium
      orbitals, based on comparison of the scalar and dipolar hyperfine components to
      atomic 77Se. Two electron oxidation of formate by the Mo(VI) state converts Mo to
      the reduced Mo(IV) state with the formate proton, Hf+, transferring to a nearby
      base Y-. Transfer of one electron to the Fe4S4 center converts Mo(IV) to the EPR
      detectable Mo(V) state. The Y- is located within magnetic contact to the [Mo-Se]
      center, as shown by its strong dipolar 1Hf hyperfine couplings. Photolysis of the
      formate-induced Mo(V) state abolishes the 1Hf hyperfine splitting from YHf,
      suggesting photoisomerizaton of this group or phototransfer of the proton to a
      more distant proton acceptor group A-. The minor effect of photolysis on the 77Se
      hyperfine interaction with [77Se] selenocysteine suggests that the Y- group is
      not the Se atom, but instead might be the imidazole ring of the His141 residue
      which is located in the putative substrate-binding pocket close to the [Mo-Se]
      center. We propose that the transfer of Hf+ from formate to the active site base
      Y- is thermodynamically coupled to two-electron oxidation of the formate
      molecule, thereby facilitating formation of CO2. Under normal physiological
      conditions, when electron flow is not limited by the terminal acceptor of
      electrons, the energy released upon oxidation of Mo(IV) centers by the Fe4S4 is
      used for deprotonation of YHf and transfer of Hf+ against the thermodynamic
      potential.

PMID- 9521674
TI  - Stability and oligosaccharide binding of the N1 cellulose-binding domain of
      Cellulomonas fimi endoglucanase CenC.
AB  - Differential scanning calorimetry has been used to study the thermal stability
      and oligosaccharide-binding thermodynamics of the N-terminal cellulose-binding
      domain of Cellulomonas fimi beta-1,4-glucanase CenC (CBDN1). CBDN1 has a
      relatively low maximum stability (delta Gmax = 33 kJ/mol = 216 J/residue at 1
      degree C and pH 6.1) compared to other small single-domain globular proteins. The
      unfolding is fully reversible between pH 5.5 and 9 and in accordance with the two
      state equilibrium model between pH 5.5 and 11. When the single disulfide bond in
      CBDN1 is reduced, the protein remains unfolded at all conditions, as judged by
      NMR spectroscopy. This indicates that the intramolecular cross-link makes a major
      contribution to the stability of CBDN1. The measured heat capacity change of
      unfolding (delta Cp = 7.5 kJ mol-1 K-1) agrees well with that calculated from the
      predicted changes in the solvent accessible nonpolar and polar surface areas upon
      unfolding. Extrapolation of the specific enthalpy and entropy of unfolding to
      their respective convergence temperature indicates that per residue unfolding
      energies for CBDN1, an isolated domain, are in accordance with those found by
      Privalov (1) for many single-domain globular proteins. DSC thermograms of the
      unfolding of CBDN1 in the presence of various concentrations of cellopentaose
      were fit to a thermodynamic model describing the linkage between protein-ligand
      binding and protein unfolding. A global two-dimensional minimization routine is
      used to regress the binding enthalpy, binding constant, and unfolding
      thermodynamics for the CBDN1-cellopentaose system. Extrapolated binding constants
      are in quantitative agreement with those determined by isothermal titration
      calorimetry at 35 degrees C.

PMID- 9521675
TI  - Mutagenesis of 3 alpha-hydroxysteroid dehydrogenase reveals a "push-pull"
      mechanism for proton transfer in aldo-keto reductases.
AB  - Rat liver 3 alpha-hydroxysteroid dehydrogenase (3 alpha-HSD, E.C. 1.1.1.213,
      AKR1C9) is a member of the aldo-keto reductase (AKR) superfamily which
      inactivates circulating steroid hormones. We have proposed a catalytic mechanism
      in which Tyr 55 acts as a general acid with its pK value being lowered by a
      hydrogen bond with Lys 84 which is salt-linked to Asp 50. To test this mechanism,
      residues at the active site were mutated and the mutant enzymes (Y55F, Y55S,
      K84M, K84R, D50N, D50E, and H117A) were purified to homogeneity from an
      Escherichia coli expression system. Spectrophotometric assays showed that
      mutations of Tyr 55 and Lys 84 gave enzymes that were apparently inactive for
      steroid oxidation and reduction. All mutants appeared inactive for steroid
      reduction. The catalytic efficiencies for steroid oxidation were reduced 4-10
      fold for the Asp 50 mutants and 300-fold for the H117A mutant. Fluorescence
      titration with NADPH demonstrated that each mutant bound cofactor unimpeded.
      Equilibrium dialysis indicated that the competitive inhibitor testosterone formed
      E.NADH.testosterone complexes only with the Y55F, Y55S, and D50N mutants with Kd
      values 10-fold greater than those for wild-type. Therefore the loss of steroid
      oxidoreductase activity observed for the Tyr 55 mutants cannot be attributed
      simply to an inability to bind steroid. Using a highly sensitive radiometric
      assay in which the conversion of [14C]-5 alpha-dihydrotestosterone (DHT) to [14C]
      3 alpha-androstanediol (3 alpha-Diol) was measured, the rate enhancement
      (kcat/knoncat) for the reaction was estimated to be 2.6 x 10(9). Using this
      assay, all mutants formed steroid product with decreases in an overall rate
      enhancement of 10(1)-10(4). It was found that Tyr 55 made the single largest
      contribution to rate enhancement. This is the first instance where point
      mutations in the conserved catalytic tetrad of an AKR yielded enzymes which were
      still catalytically active. This enabled the construction of pH vs kcat profiles
      for the reduction of [14C]-5 alpha-DHT catalyzed by the tetrad mutants. These
      profiles revealed that the titratable group assigned to the general acid (pK =
      6.50 +/- 0.42) was eliminated in the Y55F and H117A mutants. The pH-independent
      value of kcat was decreased in the H117A and Y55F mutants, by 2 and 4 log units,
      respectively. pH vs kcat(app) profiles for the oxidation of [3H]-3 alpha-Diol
      showed that the same titratable group (pK = 7.50 +/- 0.30) was eliminated in both
      the Y55F and K84M mutants but was retained in the H117A mutant. Since only the
      Y55F mutant eliminated the titratable group in both the reduction and oxidation
      directions it is assigned as the catalytic general acid/base. The differential
      effects of His 117 and Lys 84 on the ionization of Tyr 55 are explained by a
      "push-pull" mechanism in which His 117 facilitates proton donation and Lys 84
      facilitates proton removal by Tyr 55.

PMID- 9521676
TI  - Structural analysis of the P10/11-P12 RNA domain of yeast RNase P RNA and its
      interaction with magnesium.
AB  - The P10/11-P12 RNA domain of yeast RNase P contains several highly conserved
      nucleotides within a conserved secondary structure. This RNA domain is essential
      for enzyme function in vivo, where it has a demonstrated role in divalent cation
      utilization. To better understand the function of this domain, its structure and
      alterations in response to magnesium have been investigated in vitro. A secondary
      structure model of the P10/11-P12 RNA domain had been previously developed by
      phylogenetic analysis. Computer modeling and energy minimization were applied to
      the Saccharomyces cerevisiae P10/11-P12 domain to explore alternatives and
      additional interactions not predicted by the phylogenetic consensus. The working
      secondary structure models were challenged with data obtained from 1H NMR and in
      vitro chemical and enzymatic probing experiments. The solution structure of the
      isolated domain was found to conform to the phylogenetic prediction within the
      context of the holoenzyme. Structure probing data also discriminated among
      additional base contacts predicted by energy minimization. The withdrawal of
      magnesium does not appear to cause gross refolding or rearrangement of the RNA
      domain structure. Instead, subtle changes occur in the solution accessibility of
      specific nucleotide positions. Most of the conserved nucleotides reported to be
      involved in magnesium utilization in vivo also display magnesium-dependent
      changes in vitro.

PMID- 9521677
TI  - DNA minor groove binding-directed poisoning of human DNA topoisomerase I by
      terbenzimidazoles.
AB  - We have employed a broad range of spectroscopic, calorimetric, DNA cleavage, and
      DNA winding/unwinding measurements to characterize the DNA binding and
      topoisomerase I (TOP1) poisoning properties of three terbenzimidazole analogues,
      5-phenylterbenzimidazole (5PTB), terbenzimidazole (TB), and 5-(naphthyl[2,3
      d]imidazo-2-yl)bibenzimidazole (5NIBB), which differ with respect to the
      substitutions at their C5 and/or C6 positions. Our results reveal the following
      significant features. (i) The overall extent to which the three terbenzimidazole
      analogues poison human TOP1 follows the hierarchy 5PTB > TB >> 5NIBB. (ii) The
      impact of the three terbenzimidazole analogues on the superhelical state of
      plasmid DNA depends on the [total ligand] to [base pair] ratio (rbp), having no
      effect on DNA superhelicity at rbp ratios < or = 0.1, while weakly unwinding DNA
      at rbp ratios > 0.1. This weak DNA unwinding activity exhibited by the three
      terbenzimidazoles does not appear to be correlated with the abilities of these
      compounds to poison TOP1. (iii) Upon complexation with both poly(dA).poly(dT) and
      salmon testes DNA, the three terbenzimidazole analogues exhibit flow linear
      dichroism properties characteristic of a minor groove-directed mode of binding to
      these host DNA duplexes. (iv) The apparent minor groove binding affinities of the
      three terbenzimidazole analogues for the d(GA4T4C)2 duplex follow a qualitatively
      similar hierarchy to that noted above for ligand-induced poisoning of human TOP1
      namely, 5PTB > TB > 5NIBB. In the aggregate, our results suggest that DNA minor
      groove binding, but not DNA unwinding, is important in the poisoning of TOP1 by
      terbenzimidazoles.

PMID- 9521678
TI  - Pre-steady-state kinetics of nucleotide insertion following 8-oxo-7,8
      dihydroguanine base pair mismatches by bacteriophage T7 DNA polymerase exo-.
AB  - 8-Oxo-7,8-dihydroguanine (8-oxoGua) can base pair with either cytosine (C) or
      adenine (A) when replicated by DNA polymerases. The 8-oxoGua.A mismatch is
      extended in preference to the 8-oxoGua.C pair. Using a model 25-mer/36-mer DNA
      duplex containing either guanine (Gua).C, 8-oxoGua.C, or 8-oxoGua.A base pairs at
      the primer terminus and A at the standing start position, we found that the pre
      steady-state addition of dTTP opposite A following all three base pairs by
      bacteriophage T7 DNA polymerase exo- showed burst kinetics, suggesting that
      extension of all three base pairs is controlled by the rate of a step at or
      before phosphodiester bond formation. Substitution of dTTP alpha S for dTTP
      yielded modest thio effects of 1-6, suggesting that extension of all three pairs
      is limited by the rate of the conformational change prior to phosphodiester bond
      formation. Pre-steady-state values for kpol (maximum polymerization rate) were
      120, 12, and 28 s-1, and Kd values were 2, 75, and 22 microM for insertion of
      dTTP following Gua.C, 8-oxoGua.C, and 8-oxoGua.A base pairs, respectively.
      Additional analysis of extension was provided by substitution of A in the
      standing start position by 2-aminopurine (2-AP), a fluorescent base analogue.
      Comparison of rapid-quench gel-based assays with stopped-flow fluorescence
      quenching assays suggested that during addition of dTTP opposite 2-AP
      phosphodiester bond formation was rate-limiting when 8-oxoGua.C or 8-oxoGua.A
      were the preceding base pairs, while conformational change was rate-limiting when
      Gua.C was the preceding base pair. Furthermore, the difference in apparent
      conformational change rates for addition of dTTP opposite 2-AP following the 8
      oxoGua base pairs was greater than the differences in their phosphodiester bond
      formation rates, suggesting that discrimination in extension may be influenced
      more by conformational change rates than the rates of phosphodiester bond
      formation in this mispaired system.

PMID- 9521679
TI  - Oligomerization of endogenous and synthetic amyloid beta-protein at nanomolar
      levels in cell culture and stabilization of monomer by Congo red.
AB  - Amyloid beta-proteins (A beta) are proteolytic fragments of the beta-amyloid
      precursor protein (beta APP) that are secreted by mammalian cells throughout life
      but also accumulate progressively as insoluble cerebral aggregates in Alzheimer's
      disease (AD). Because mounting evidence indicates that A beta aggregation and
      deposition are early, critical features of AD leading to neurotoxicity, many
      studies of A beta aggregation have been conducted using synthetic peptides under
      generally nonphysiological conditions and concentrations. We recently described
      the oligomerization of A beta peptides secreted by beta APP-expressing cells at
      low nanomolar (20-30 ng/mL) levels into sodium dodecyl sulfate- (SDS-) stable
      oligomers of 6-16 kDa. Here, we extensively characterize this in vitro system and
      show that the amyloid binding dye, Congo red, acts to markedly decrease
      oligomer/monomer ratios by stabilizing the 4 kDa A beta monomers (ID50
      approximately equal to 3.4 microM). Addition of radioiodinated synthetic A beta 1
      40 to the cultures or to their conditioned media at physiological concentrations
      (0.25-2.5 nM) reveals that it undergoes progressive aggregation into SDS-stable
      oligomers of 6-25 kDa during brief (approximately 4 h) incubation at 37 degrees
      C, and this is inhibitable by Congo red. The level of A beta oligomers can be
      quantitated in the Chinese hamster ovary (CHO) conditioned medium by size
      exclusion chromatography as well as by SDS-polyacrylamide gel electrophoresis
      (PAGE), and comparison of these two methods suggests that aggregation of A beta
      into higher molecular weight polymers that are not detectable by SDS-PAGE occurs
      in the cultures. We conclude that both endogenous and synthetic A beta can
      assemble into stable oligomers at physiological concentrations in cell culture,
      providing a manipulable system for studying the mechanism of early A beta
      aggregation and identifying inhibitors thereof under biologically relevant
      conditions.

PMID- 9521680
TI  - Photoaffinity labeling of the human receptor for urokinase-type plasminogen
      activator using a decapeptide antagonist. Evidence for a composite ligand-binding
      site and a short interdomain separation.
AB  - Binding of urokinase-type plasminogen activator (uPA) to its cellular receptor
      (uPAR) renders the cell surface a favored site for plasminogen activation.
      Recently, a 15-mer peptide antagonist of the uPA-uPAR interaction, with an IC50
      value of 10 nM, was identified using phage display technology [Goodson, R. J.,
      Doyle, M. V., Kaufman, S. E., and Rosenberg, S. (1994) Proc. Natl. Acad. Sci. 91,
      7129-7133]. In the present study, the molecular aspects of the interaction
      between this peptide and uPAR have been investigated. We have characterized the
      real-time receptor binding kinetics for the antagonist using surface plasmon
      resonance and identified critical residues by alanine replacements. The minimal
      peptide antagonist thus derived (SLNFSQYLWS) was rendered photoactivatable by
      replacing residues important for uPAR binding with photochemically active
      derivatives of phenylalanine containing either (trifluoromethyl)diazirine or
      benzophenone. These peptides incorporated covalently into purified soluble uPAR
      upon photoactivation, and this was inhibited by preincubation with receptor
      binding derivatives of uPA. The intact three-domain structure of uPAR was
      essential for efficient photoaffinity labeling. Proteolytic domain mapping using
      chymotrypsin revealed a specific labeling of both uPAR domain I and domains II +
      III dependent on the position of the photoprobe in the antagonist. On the basis
      of these studies, we propose the existence of a composite ligand binding site in
      uPAR combined of residues located in distinct structural domains. According to
      this model, a close spatial proximity between uPAR domain I and either domains II
      or III in intact uPAR is required for the assembly of this composite binding
      site. Since the receptor binding properties of the peptide antagonist closely
      mimic those of uPA itself, these two ligands presumably share coincident binding
      site in uPAR.

PMID- 9521681
TI  - Solution structure of Ace-AMP1, a potent antimicrobial protein extracted from
      onion seeds. Structural analogies with plant nonspecific lipid transfer proteins.
AB  - The three-dimensional solution structure of Ace-AMP1, an antifungal protein
      extracted from onion seeds, was determined using 1H NMR spectroscopy and
      molecular modeling. This cationic protein contains 93 amino acid residues and
      four disulfide bridges. Its structure was determined from 1260 NOE-derived
      distance restraints and 173 dihedral restraints derived from NOEs and 3JCaHNH
      coupling constants. The global fold involves four helical segments connected by
      three loops and a C-terminal tail without regular secondary structures, except
      for a 3(10)-helix turn and a beta-turn. The most striking feature is the absence
      of any continuous cavity running through the whole molecule as found in recently
      determined structures of nonspecific transfer proteins extracted from wheat and
      maize seeds, although their global folds are very similar. Consistent with the
      absence of a cavity in the core of Ace-AMP1, it was found that this protein, in
      contrast to ns-LTPs, does not bind fluorescently labeled phospholipids in
      solution. On the other hand, Ace-AMP1 is able to interact with phospholipid
      membranes as shown by the release of carboxyfluorescein from the lumen of
      artificial liposomes and by the induction of alterations in fluorescence
      polarization of fluorescently labeled phospholipids embedded in artificial
      liposomes.

PMID- 9521682
TI  - Solution studies of isepamicin and conformational comparisons between isepamicin
      and butirosin A when bound to an aminoglycoside 6'-N-acetyltransferase determined
      by NMR spectroscopy.
AB  - NMR spectroscopy, combined with molecular modeling, was used to determine the
      conformations of isepamicin and butirosin A in the active site of aminoglycoside
      6'-N-acetyltransferase-Ii [AAC-(6')-Ii]. The results suggest two enzyme-bound
      conformers for isepamicin and one for butirosin A. The dihedral angles that
      describe the glycosidic linkage between the A and B rings for the two conformers
      of AAC(6')-Ii-bound isepamicin were phi AB = -7.9 +/- 2.0 degrees and psi AB = 
      46.2 +/- 0.6 degrees for conformer 1 and phi AB = -69.4 +/- 2.0 degrees and psi
      AB = -57.7 +/- 0.5 degrees for conformer 2. Unrestrained molecular dynamics
      calculations showed that these distinct conformers are capable of interconversion
      at 300 K. When superimposed at the 2-deoxystreptamine ring, one enzyme-bound
      conformer of isepamicin (conformer 1) places the reactive 6' nitrogen in a
      similar position as that of butirosin A. Conformer 2 of AAC(6')-Ii-bound
      isepamicin may represent an unproductive binding mode. Unproductive binding modes
      (to aminoglycoside modifying enzymes) could provide one reason isepamicin remains
      one of the more effective aminoglycoside antibiotics. The enzyme-bound
      conformation of butirosin A yielded an orthogonal arrangement of the 2,6-diamino
      2,6-dideoxy-D-glucose and D-xylose rings, as opposed to the parallel arrangement
      which was observed for this aminoglycoside in the active site of an
      aminoglycoside 3'-O-phosphotransferase [Cox, J. R., and Serpersu, E. H. (1997)
      Biochemistry 36, 2353-2359]. The complete proton and carbon NMR assignments of
      the aminoglycoside antibiotic isepamicin at pH 6.8 as well as the pKa values for
      it's amino groups are also reported.

PMID- 9521683
TI  - 13C NMR, X-ray, and differential scanning calorimetry investigations of truncated
      BPTI (aprotinin) analogues.
AB  - Truncated BPTI missing residues 1 and 2 is investigated together with variants
      thereof (Lys-15, Arg-17, and Arg-42 are replaced by other residues in various
      combinations). A comparison of the X-ray structure of BPTI with that of 3
      58BPTI(K15R,R17A,R42S) shows only minor variations for the backbone, but the lack
      of salt bridge between the terminals and the lack of two N-terminal residues
      provide a structure open at one end. Comparisons of amide exchange rates show a
      dramatic increase for the most slowly exchanging NH protons of 3-58BPTI and the
      analogues thereof, as compared to those of the wild-type despite only small
      differences in the structures. The amide exchange rates for truncated analogues
      increase with decreasing TTEP (temperature top endothermic peak) values. On the
      basis of the known structural changes comparisons to 13C chemical shifts are
      made. 13C chemical shifts are assigned using the D-isotope and HMBC techniques.
      Excellent resolution is obtained in these 1D natural abundance spectra. 13C NMR
      chemical shifts are shown to be able to gauge structural changes. A comparison of
      13C chemical shifts of WT BPTI (aprotinin) and 3-58BPTI reveals effects caused by
      (i) the removal of the salt bridge of the terminii, (ii) the charge of the N
      terminus, and (iii) the increased mobility of the side chain of Tyr-23. Small
      effects are also seen due to a conformational change of the aromatic ring of Phe
      4. Ring current shifts at 13C chemical shifts are calculated. The difference in
      the calculated ring current effects are small comparing the wild-type with 3
      58BPTI(K15R,R17A,R42S) provided the structures are relaxed. Protein unfolding as
      a function of pH and temperature is studied by DSC. Unfolding occurs at lower
      temperature with N-terminally truncated analogues, and the maximum is shifted
      toward higher pH.

PMID- 9521684
TI  - Crystal structure of human arylsulfatase A: the aldehyde function and the metal
      ion at the active site suggest a novel mechanism for sulfate ester hydrolysis.
AB  - Human lysosomal arylsulfatase A (ASA) is a prototype member of the sulfatase
      family. These enzymes require the posttranslational oxidation of the -CH2SH group
      of a conserved cysteine to an aldehyde, yielding a formylglycine. Without this
      modification sulfatases are catalytically inactive, as revealed by a lysosomal
      storage disorder known as multiple sulfatase deficiency. The 2.1 A resolution X
      ray crystal structure shows an ASA homooctamer composed of a tetramer of dimers,
      (alpha 2)4. The alpha/beta fold of the monomer has significant structural analogy
      to another hydrolytic enzyme, the alkaline phosphatase, and superposition of
      these two structures shows that the active centers are located in largely
      identical positions. The functionally essential formylglycine is located in a
      positively charged pocket and acts as ligand to an octahedrally coordinated metal
      ion interpreted as Mg2+. The electron density at the formylglycine suggests the
      presence of a 2-fold disordered aldehyde group with the possible contribution of
      an aldehyde hydrate, -CH(OH)2, with gem-hydroxyl groups. In the proposed
      catalytic mechanism, the aldehyde accepts a water molecule to form a hydrate. One
      of the two hydroxyl groups hydrolyzes the substrate sulfate ester via a
      transesterification step, resulting in a covalent intermediate. The second
      hydroxyl serves to eliminate sulfate under inversion of configuration through C-O
      cleavage and reformation of the aldehyde. This study provides the structural
      basis for understanding a novel mechanism of ester hydrolysis and explains the
      functional importance of the unusually modified amino acid.

PMID- 9521685
TI  - NarL dimerization? Suggestive evidence from a new crystal form.
AB  - The structure of the Escherichia coli response regulator NarL has been solved in
      a new, monoclinic space group, and compared with the earlier orthorhombic crystal
      structure. Because the monoclinic crystal has two independent NarL molecules per
      asymmetric unit, we now have three completely independent snapshots of the NarL
      molecule: two from the monoclinic form and one from the orthorhombic. Comparison
      of these three structures shows the following: (a) The pairing of N and C domains
      of the NarL molecule proposed from the earlier analysis is in fact correct,
      although the polypeptide chain connecting domains was, and remains, disordered
      and not completely visible. The new structure exhibits identical relative
      orientation of N and C domains, and supplies some of the missing residues,
      leaving a gap of only seven amino acids. (b) Examination of corresponding
      features in the three independent NarL molecules shows that deformations in
      structure produced by crystal packing are negligible. (c) The "telephone
      receiver" model of NarL activation is confirmed. The N domain of NarL blocks the
      binding of DNA to the C domain that would be expected from the helix-turn-helix
      structure of the C domain. Hence, binding can only occur after significant
      displacement of N and C domains. (d) NarL monomers have a strong tendency toward
      dimerization involving contacts between helixes alpha 1 in the two monomers, and
      this may have mechanistic significance in DNA binding. Analogous involvement of
      helix alpha 1 in intermolecular contacts is also found in UhpA and in the
      CheY/CheZ complex.

PMID- 9521686
TI  - Crystal structure of yeast thymidylate kinase complexed with the bisubstrate
      inhibitor P1-(5'-adenosyl) P5-(5'-thymidyl) pentaphosphate (TP5A) at 2.0 A
      resolution: implications for catalysis and AZT activation.
AB  - The crystal structure of yeast thymidylate kinase (TmpK) complexed with the
      bisubstrate inhibitor P1-(5'-adenosyl) P5-(5'-thymidyl) pentaphosphate (TP5A) was
      determined at 2.0 A resolution. In this complex, TmpK adopts a closed
      conformation with a region (LID) of the protein closing upon the substrate and
      forming a helix. The interactions of TmpK and TP5A strongly suggest that arginine
      15, which is located in the phosphate binding loop (P-loop) sequence, plays a
      catalytic role by interacting with an oxygen atom of the transferred phosphoryl
      group. Unlike other nucleoside monophosphate kinases where basic residues from
      the LID region participate in stabilizing the transition state, TmpK lacks such
      residues in the LID region. We attribute this function to Arg 15 of the P-loop.
      TmpK plays an important role in the phosphorylation of the AIDS prodrug AZT. The
      structures of TmpK with dTMP and with AZT-MP [Lavie, A., et al. (1997) Nat.
      Struct. Biol. 4, 601-604] implicate the movement of Arg15 in response to AZT-MP
      binding as an important factor in the 200-fold reduced catalytic rate with AZT
      MP. TmpK from Escherichia coli lacks this arginine in its P-loop while having
      basic residues in the LID region. This suggested that, if such a P-loop movement
      were to occur in the E. coli TmpK upon AZT-MP binding, it should not have such a
      detrimental effect on catalysis. This hypothesis was tested, and as postulated,
      E. coli TmpK phosphorylates AZT-MP only 2.5 times slower than dTMP.

PMID- 9521687
TI  - Local dynamics and stability of apocytochrome b562 examined by hydrogen exchange.
AB  - Cytochrome b562 is a heme-binding protein consisting of four helices folded into
      a classic helix bundle motif. Though retaining much of the topology of the
      holoprotein, apocytochrome b562 displays physical features commonly associated
      with so-called protein molten globules. Here, the stability and dynamics of this
      "structured" molten globule are probed by examination of the dependence of its
      hydrogen exchange behavior upon the presence of a chemical denaturant. Compared
      to other systems studied in this manner, apocytochrome b562 displays a limited
      dynamic range of hydrogen exchange rates and the analysis required the
      development of a quantitative approach. The protein is found to have three
      regions of subglobal cooperative stability. The most stable region, or core, is
      composed of the central two helices of the bundle, with the N- and C-terminal
      helices being of independent and lower stability. The dependence of the global
      unfolding free energy upon denaturant concentration indicates the applicability
      of a binding model and explains the observed difference between global unfolding
      free energies obtained by the linear extrapolation method and those obtained by
      calorimetry and hydrogen exchange. These observations place a significant
      restraint upon the type of folding pathway that is operative for this protein and
      suggest that that the N- and C-terminal helices fold and unfold independently of
      the core of the molecule.

PMID- 9521689
TI  - Destabilized PCNA trimers suppress defective Rfc1 proteins in vivo and in vitro.
AB  - Replication factor C (RFC) and the proliferating cell nuclear antigen (PCNA) are
      two essential DNA polymerase accessory proteins that are required for numerous
      aspects of DNA metabolism including DNA replication, DNA repair, and telomere
      metabolism. PCNA is a homotrimeric ring-shaped sliding DNA clamp that can
      facilitate DNA replication by tethering DNA polymerase delta or DNA polymerase
      epsilon to the DNA template. RFC is the 5-subunit multiprotein complex that loads
      PCNA onto DNA at primer-template junctions in an ATP-dependent reaction. All five
      of the RFC subunits share a set of related sequences (RFC boxes) that include
      nucleotide-binding consensus sequences. We report here that a mutation in the
      gene encoding the large subunit of yeast RFC gives rise to DNA metabolism defects
      that can be observed in vivo and in vitro. The rfc1-1 substitution (D513N) lies
      within the widely conserved RFC box VIII consensus sequence and results in
      phenotypes including DNA replication defects, increased sensitivity to DNA
      damaging agents, and elongated telomeres. Mutant Rfc1-1 complexes exhibit in
      vitro DNA replication defects that are sensitive to ATP concentrations, and these
      defects can be suppressed by mutant PCNA proteins which contain substitutions
      that destabilize the homotrimeric sliding DNA clamp.

PMID- 9521688
TI  - Identification of a 13 amino acid peptide mimetic of erythropoietin and
      description of amino acids critical for the mimetic activity of EMP1.
AB  - To obtain information about the functional importance of amino acids required for
      effective erythropoietin (EPO) mimetic action, the conserved residues of a
      peptide mimetic of EPO, recently discovered by phage display, were subjected to
      an alanine replacement strategy. Further, to identify a minimal mimetic peptide
      sequence, a series of truncation peptides has been generated. One EPO mimetic
      peptide sequence, EMP1, was targeted and more than 25 derivatives of this
      sequence were evaluated for their ability to compete with [125I]EPO for receptor
      binding and for their ability to support the proliferation of two EPO-responsive
      cell lines. Two hydrophobic amino acids, Tyr4 and Trp13, appear essential for
      mimetic action, and aromatic residues appear to be important at these sites.
      These findings are consistent with the previously reported X-ray crystal
      structure of EMP1 complexed with the extracellular domain of the EPO receptor
      (EPO binding protein; EBP). In our efforts to define the structural elements
      required for EPO mimetic action, a 13 amino acid peptide was identified which
      possesses mimetic properties and contains a minimal agonist epitope. The ability
      of this peptide to effectively serve as a mimetic capable of the induction of EPO
      responsive cell proliferation appears to reside within a single residue,
      equivalent to position Tyr4 of EMP1, when present in a sequence that includes the
      cyclic core peptide structure. Although these peptides are less potent than EPO,
      they should serve as an excellent starting point for the design of compounds with
      EPO mimetic activity.

PMID- 9521691
TI  - Lysine and arginine residues in the N-terminal 18% of apolipoprotein B are
      critical for its binding to microsomal triglyceride transfer protein.
AB  - Apolipoprotein B (apoB) and microsomal triglyceride transfer protein (MTP) are
      essential for the efficient assembly and secretion of triglyceride-rich
      lipoproteins. We have presented evidence for a high-affinity interaction between
      these proteins [Hussain, M. M., et al. (1997) Biochemistry 36, 13060-13067]. In
      this study, we used chemically modified low-density lipoproteins (LDL) and
      recombinant human apoB18 to identify amino acid residues in apoB that are
      critical for its interactions with MTP. Acetoacetylation of 74% of lysine
      residues and cyclohexanedione modification of 54% of arginine residues completely
      abolished the interactions between LDL and MTP. Regeneration of lysine and
      arginine residues by hydroxylamine treatment completely restored the binding of
      modified LDL to MTP. Carboxyethylation of all the histidine residues decreased,
      but did not abolish, apoB-MTP interactions. In contrast, glycine methyl ester
      modifications of aspartic and glutamic acid residues, up to 38-44%, had no effect
      on LDL-MTP interactions. Furthermore, modification of lysine and arginine, but
      not the aspartic and glutamic acid, residues in apoB18 also completely abolished
      its interactions with MTP. These studies indicated that lysine and arginine, but
      not aspartic and glutamic acid, residues are critical for apoB-MTP interactions,
      whereas histidine residues are not as critical. Since lysine and arginine
      residues in apoB are known to interact with the LDL receptors and heparin, we
      studied the effect of different glycosaminoglycans on apoB-MTP interactions.
      Glycosaminoglycans had no significant inhibitory effect on apoB-MTP interactions,
      suggesting that the lysine and arginine residues crucial for apoB-MTP
      interactions are different from those that interact with the LDL receptor and
      heparin. The lysine and arginine residues in apoB18 may directly interact with
      negatively charged residues in the MTP molecule, or they may function to maintain
      the conformation of the recognition site.

PMID- 9521690
TI  - Analysis of the ligand binding site in Fas (CD95) by site-directed mutagenesis
      and comparison with TNFR and CD40.
AB  - Fas and its ligand (FasL) are members of the tumor necrosis factor receptor
      (TNFR) and tumor necrosis factor (TNF) superfamilies, respectively. Fas-FasL
      interactions trigger controlled cell death (apoptosis) in the immune system and
      thus play a key role in the regulation of immune responses. Structural details of
      the Fas-Fas ligand interaction are currently unknown. Previously, six Fas
      residues were identified by mutagenesis as important for ligand binding. We have
      now extended our mutagenesis analysis and identified additional residues which
      contribute to the Fas-FasL interaction. Candidate and control residues were
      selected based on a molecular model of the Fas extracellular region. Although
      residues in all three extracellular domains were identified to contribute to
      binding, the Fas-FasL interaction is centered on the second TNFR-like domain.
      Important residues were compared to critical positions in TNFR and CD40, another
      member of the TNFR family.

PMID- 9521692
TI  - Evidence for lipid-dependent structural changes in specific domains of
      apolipoprotein B100.
AB  - The structural organization and stability of apoB100 in complexes containing
      triglyceride (TG) and phospholipid have been examined. LDL was delipidated to
      form aqueous soluble apoB100-TG complexes that retain approximately 70% of LDL
      TG, but contain no other lipids. The apoB100-TG complexes exhibited reduced
      amphipathic alpha-helical content (17%) and net negative charge (-2.9 mV) as
      compared to native LDL-apoB100 (49% and -6 mV, respectively). Of 28 anti-apoB
      monoclonal antibodies tested, 15 showed partial or full reactivity with apoB100
      TG. The immunoreactive epitopes of apoB100-TG were restricted to those situated
      in either the amino terminal globular domain (4 of 6) or in regions of apoB100
      that are predicted to be composed of amphipathic beta-strands (11 of 13).
      Incubation of the apoB100-TG complex with palmitoyloleoylphosphatidylcholine
      (POPC) spontaneously (< 10 min) formed homogeneous lipoproteins (20 nm) that
      contained approximately 300 molecules of POPC per particle (apoB100-PC).
      Phospholipidation of apoB100-TG complexes partially recovered the alpha-helical
      content (34%) and net negative charge (-4.9 mV) of the native LDL and restored
      resistance of apoB100 to denaturation by guanidine HCl (5.8 M). Addition of
      phospholipids to apoB100-TG also increased the immunoreactivity of specific
      epitopes that are located primarily in regions of apoB100 that are thought to be
      constituted of amphipathic beta-strands. The effects of TG and phospholipid on
      apoB100 conformation appear to be highly domain-specific. On the basis of these
      results, we propose that the beta-strands of apoB100 may represent a nonflexible
      lipid-associating backbone, while the amphipathic alpha-helical domains may
      represent flexible lipid-binding regions that allow the particle to accommodate
      varying amounts of lipid.

PMID- 9521693
TI  - Restoration of catalytic activity beyond wild-type level in glucoamylase from
      Aspergillus awamori by oxidation of the Glu400-->Cys catalytic-base mutant to
      cysteinesulfinic acid.
AB  - Glucoamylase catalyzes the hydrolysis of glucosidic bonds with inversion of the
      anomeric configuration. Site-directed mutagenesis and three-dimensional structure
      determination of the glucoamylase from Aspergillus awamori previously identified
      Glu179 and Glu400 as the general acid and base catalyst, respectively. The
      average distance between the two carboxyl groups was measured to be 9.2 A, which
      is typical for inverting glycosyl hydrolases. In the present study, this distance
      was increased by replacing the catalytic base Glu400 with cysteine which was then
      oxidized to cysteinesulfinic acid. Initially, this oxidation occurred during
      attempts to carboxyalkylate the Cys400 residue with iodoacetic acid, 3
      iodopropionic acid, or 4-bromobutyric acid. However, endoproteinase Lys-C
      digestion of modified glucoamylase followed by high-pressure liquid
      chromatography in combination with matrix-assisted laser desorption
      ionization/time-of-flight mass spectrometry on purified peptide fragments
      demonstrated that all enzyme derivatives contained the cysteinesulfinic acid
      oxidation product of Cys400. Subsequently, it was demonstrated that treatment of
      Glu400-->Cys glucoamylase with potassium iodide in the presence of bromine
      resulted in complete conversion to the cysteinesulfinic acid product. As
      expected, the catalytic base mutant Glu400-->Cys glucoamylase had very low
      activity, i.e., 0.2% compared to wild-type. The oxidation of Cys400 to
      cysteinesulfinic acid, however, restored activity (kcat) on alpha-1,4-linked
      substrates to levels up to 160% of the wild-type glucoamylase which corresponded
      to approximately a 700-fold increase in the kcat of the Glu400-->Cys mutant
      glucoamylase. Whereas Glu400-->Cys glucoamylase was much less thermostable and
      more sensitive to guanidinium chloride than the wild-type enzyme, the oxidation
      to cysteinesulfinic acid was accompanied by partial recovery of the stability.

PMID- 9521694
TI  - Enzymatic properties of the cysteinesulfinic acid derivative of the catalytic
      base mutant Glu400-->Cys of glucoamylase from Aspergillus awamori.
AB  - The pKa of the catalytic base was lowered and its distance to the general acid
      catalyst, Glu179, was increased in the glucoamylase from Aspergillus awamori by
      replacing the catalytic base Glu400 with cysteine followed by oxidation to
      cysteinesulfinic acid [Fierobe, H.-P., Mirgorodskaya, E., McGuire, K. A.,
      Roepstorff, P., Svensson, B. and Clarke, A. J. (1998) Biochemistry 37, 3743-3752.
      1H NMR spectroscopy demonstrated that the oxidized mutant Glu400-->Cys-SO2H
      glucoamylase, like the wild-type, catalyzed hydrolysis with inversion of the
      anomeric configuration of the product. Relative to the catalytic base mutant
      Glu400-->Cys, the Cys400-SO2H glucoamylase had 700 times higher kcat toward
      maltose, while K(m) was unchanged. Compared to wild-type glucoamylase, the Cys400
      SO2H derivative had kcat values of 150-190% and 85-320% on malto- and
      isomaltooligosaccharides, respectively, while K(m) values were similar to those
      of wild-type with the two disaccharides and 3.5-5.5- and 1.8-2.5-fold higher for
      the longer malto- and isomaltooligosaccharides substrates, respectively. The pH
      activity dependence at saturating concentration of maltose indicated that the pKa
      of the catalytic base Cys400-SO2H was about 0.5 pH unit lower than that of wild
      type Glu400. The Ki of Cys400-SO2H glucoamylase for the pseudotetrasaccharide and
      potent inhibitor acarbose increased more than 10(4)-fold, but Ki values of the
      mono- and disaccharide analogues 1-deoxynojirimycin and beta-O
      methylacarviosinide were unchanged, suggesting perturbation at binding subsites
      beyond the catalytic center. A distinct property of Cys400-SO2H glucoamylase was
      the catalysis of the condensation of beta-D-glucopyranosyl fluoride and
      subsequent hydrolysis of the product to beta-glucose, under conditions where this
      was not detected for the wild-type enzyme.

PMID- 9521695
TI  - Regeneration of bovine pancreatic ribonuclease A: identification of two
      nativelike three-disulfide intermediates involved in separate pathways.
AB  - During the regeneration of bovine pancreatic ribonuclease A (RNase A) from the
      reduced to the native form with mixtures of oxidized and reduced dithiothreitol
      at 25 degrees C, pH 8.0, the disulfide-containing protein intermediates achieve a
      steady-state distribution. By manipulating the redox conditions after the
      attainment of the steady-state condition, it has been possible to kinetically
      trap and, thereby, isolate and identify the disulfide-bonded species that follow
      the rate-determining step in the regeneration pathway. Two three-disulfide
      species have been identified by peptide mapping. Both species contain three
      native disulfide-bond pairings, one lacks the 65-72 disulfide bond (des-[65-72]),
      and the other lacks the 40-95 disulfide bond (des-[40-95]). These species are the
      same as those identified during the reduction of RNase A. By restarting the
      regeneration process from isolated des-[65-72] and des-[40-95], it is shown that
      both intermediates lie directly on regeneration pathways.

PMID- 9521696
TI  - Regeneration of bovine pancreatic ribonuclease A: detailed kinetic analysis of
      two independent folding pathways.
AB  - The regeneration of bovine pancreatic ribonuclease A (RNase A) from the reduced
      to the native form with mixtures of oxidized and reduced dithiothreitol at 25
      degrees C, pH 8.0, proceeds through two separate pathways in which separate
      nativelike three-disulfide species are populated. The populations of these two
      three-disulfide species during the regeneration process have been monitored
      directly through the use of a reduction pulse. A detailed kinetic analysis of the
      regeneration process using improved experimental procedures and data analysis has
      been carried out to obtain rate constants for disulfide interconversion among the
      various disulfide-bonded intermediates. This analysis indicates that these two
      pathways can account for essentially 100% of the native protein regenerated and
      that the relative amount of native protein regenerated through these two pathways
      is insensitive to the redox conditions used. These results indicate that the rate
      determining step in both pathways involves formation of the nativelike three
      disulfide species, a step in which most of the conformational folding takes
      place. The experimentally determined rate constants indicate that these two
      pathways are sufficient to explain the differences in the temperature dependence
      of the regeneration rate with different redox reagents. In addition, the
      population of a fully oxidized species that contains three native disulfide
      bonded pairs and a dithiothreitol bridging cysteines 65 and 72 has been observed.

PMID- 9521697
TI  - Stopped-flow analysis of CO and NO binding to inducible nitric oxide synthase.
AB  - The oxygenase domain (amino acids 1-498) of inducible nitric oxide synthase
      (iNOSox) is a hemeprotein that binds L-arginine (L-Arg) and tetrahydrobiopterin
      (H4B). During NO synthesis, the heme iron must bind and activate O2, but it also
      binds self-generated No to form an inactive complex. To better understand how L
      Arg and H4B affect heme iron function in iNOSox, we utilized stopped-flow
      spectroscopy to study heme reactivity with CO and NO and the properties of the
      resulting CO and NO complexes. CO and NO binding to ferrous and ferric (NO only)
      iNOSox and subsequent complex stability was studied under four conditions: in the
      absence of L-Arg and H4B and in the presence of either or both molecules. Ferric
      iNOSox without L-Arg or H4B was dimeric and contained low-spin heme iron, while
      in H4B- or L-Arg-saturated iNOSox, the heme iron was partially or almost
      completely high-spin, respectively. In the presence of L-Arg or H4B, the rate of
      CO binding to ferrous iNOSox was slowed considerably, indicating that these
      molecules restrict CO access to the heme iron. In contrast, rates of NO binding
      were minimally affected. Under all conditions, the off rates for CO and NO were
      very high as compared to other hemeproteins. The six-coordinate FeII-CO and -NO
      complexes that initially formed were unstable and converted either slowly (CO) or
      quickly (NO) to their respective 5-coordinate complexes. However, this transition
      was largely prevented by either L-Arg or H4B and was reversed upon air oxidation
      of the complex in the presence of these molecules. Thus, H4B and L-Arg both
      promote a conformational change in the distal heme pocket of iNOSox that can
      greatly reduce ligand access to the heme iron. The ability of H4B and L-Arg to
      prevent formation of a five-coordinate heme Fe-NO complex, along with the high
      off rates observed for NO, help explain why iNOS can remain active despite
      forming a complex with NO during its normal catalysis.

PMID- 9521698
TI  - Regulation of N-arginine dibasic convertase activity by amines: putative role of
      a novel acidic domain as an amine binding site.
AB  - Peptide sequence analysis and cDNA cloning indicate that a previously described
      mouse arginine-specific dibasic cleaving enzyme (dynorphin converting enzyme)
      [Csuhai et al. (1995) Biochemistry 34, 12411] is the homologue of N-arginine
      dibasic convertase (NRDc) isolated from rat testis [Chesneau et al. (1994) J.
      Biol. Chem. 269, 2056]. A mouse NRDc cDNA exhibited 98% amino acid identity with
      the rat cDNA. However, within a 74 residue acidic stretch, this identity drops to
      82%. Likewise, the corresponding acidic stretch of human NRDc is only 73%
      identical with that of rat NRDc. To reconcile previously observed kinetic
      differences between rat and mouse NRDc, the hydrolysis of peptide substrates by
      the rat, human, and mouse enzymes was compared using phosphate and Tris as
      buffers. Although the three NRDc's behaved similarly, Tris had a pronounced
      effect on the kinetics of peptide hydrolysis. With BAM-8, alpha-neoendorphin, and
      dynorphin B as substrates, Tris increased KM up to 40-fold with little change in
      Vmax, while with dynorphin A or somatostatin 28 as substrate, Tris caused a
      decrease in KM of up to 100 fold, again with only a modest change in Vmax. Other
      amines, including the polyamines putrescine, spermidine, and spermine, all
      affected NRD convertase activity. It is proposed that amines bind to the acidic
      stretch found in NRDc, and that quantitative differences in the sensitivity to
      amines between the rat, mouse, and human enzymes can be at least partially
      accounted for by differences in their acidic stretch. The role of polyamines as
      physiological modulators of N-arginine dibasic convertase is considered.

PMID- 9521699
TI  - Phosphorylation of the cAMP response element binding protein CREB by cAMP
      dependent protein kinase A and glycogen synthase kinase-3 alters DNA-binding
      affinity, conformation, and increases net charge.
AB  - The cAMP response element binding protein CREB activates the transcription of
      genes in response to phosphorylation by cAMP-dependent protein kinase A (PKA) and
      other protein kinases. Phosphorylated CREB activates transcription by recruiting
      transcriptional co-activators such as the CREB binding protein. Here, we describe
      experiments that analyze the effects of phosphorylation on the DNA binding
      affinity of CREB and the structural characteristics of the CREB/DNA complex in
      solution. Analysis of deletion mutants of CREB indicate that amino acid sequences
      within the transactivation domain promote high-affinity binding of CREB to
      fluorescently labeled oligonucleotides containing cAMP response elements. In
      vitro experiments indicate that phosphorylation is processive between PKA as the
      initial kinase and glycogen synthase kinase-3 (GSK-3) but not casein kinase II as
      the secondary kinase. Fluorescent electrophoretic mobility shift assays show that
      phosphorylation by PKA results in a 3-5-fold increase in the binding affinity of
      CREB to both the symmetrical somatostatin CRE (SMS-CRE) and the asymmetric
      somatostatin upstream element (SMS-UE). Processive phosphorylation of CREB by GSK
      3 attenuates the enhanced DNA binding in response to PKA thus acts as an
      inhibitor of PKA-induced binding. Ferguson plot analyses demonstrate that
      phosphorylation of CREB by PKA and GSK-3 result in an increase in the spherical
      size and the net positive surface charge of the CREB/DNA complex. Moreover, these
      analyses uncovered the unexpected finding that CREB associates as a tetramer both
      in the presence and absence of DNA. These findings suggest a model by which
      phosphorylation of CREB alters the secondary structure and charge characteristics
      of the CREB/DNA complex resulting in an alteration in binding affinity.

PMID- 9521700
TI  - ATP cross-linked to Escherichia coli single-strand DNA-binding protein can be
      utilized by the catalytic center of primase as initiating nucleotide for primer
      RNA synthesis on phage G4oric template.
AB  - We report a new observation of the role of Escherichia coli single-strand DNA
      binding protein (SSB) in synthesis of primer RNA (pRNA) catalyzed by.E.coli
      primase on the SSB-coated phage G4oric template. Using a set of ATP priming
      substrates with reactive groups attached to the 5' gamma-phosphate on different
      length "arms", we have demonstrated that, in the primase/SSB/G4oric pRNA
      synthesis complex, ATP cross-linked to both primase and SSB could be equally
      utilized as initiating nucleotide for pRNA synthesis. The distance between SSB
      surface and alpha-phosphorus of the priming substrate was estimated to be less
      than 7 A. ATP cross-linked to primase and SSB can be further elongated in the
      presence of other NTPs, giving almost identical patterns of covalently attached
      pRNAs of up to 12 nucleotides in length. The regions of primase and SSB with
      cross-linked ATP that can be used for pRNA synthesis are, therefore, arranged in
      a similar way relative to the active center of pRNA synthesis. The pRNA
      covalently linked to SSB was localized, mapping between Met48 and Trp88. This
      observation raises the possibility that SSB may play an active role in the
      initiation of pRNA synthesis in this system.

PMID- 9521701
TI  - Mammalian DNA topoisomerase I activity and poisoning by camptothecin are
      inhibited by simian virus 40 large T antigen.
AB  - DNA topoisomerase I (top1) is a ubiquitous enzyme that forms reversible DNA
      single-strand breaks (cleavage complexes) and plays a role in transcription, DNA
      replication, and repair. Top1 is the target of camptothecins which selectively
      trap top1 cleavage complexes and represent a novel class of anticancer drugs
      active against human solid tumors. The present study demonstrates that
      recombinant large T antigen (T-Ag), a virus encoded helicase with strong affinity
      for tumor suppressors and cell cycle- and replication-related proteins,
      suppresses top1 cleavage complexes and top1 catalytic activity. This top1
      suppressive activity is probably not due to T-Ag binding to DNA, as a T-Ag
      truncation mutant containing only the first 246 amino acids and deficient in DNA
      binding also inhibited top1, and the inhibition was independent of ATP. T-Ag also
      antagonized and reversed the trapping of top1 cleavage complexes by camptothecin.
      These results demonstrate a functional interaction between T-Ag and top1: they
      also suggest the importance of top1-protein interactions for the regulation of
      DNA replication and modulation of camptothecin activity.

PMID- 9521702
TI  - Production and purification of recombinant 2'-5' oligoadenylate synthetase and
      its mutants using the baculovirus system.
AB  - Investigation of the structure-function relationship of the 2'-5' oligoadenylate
      [2-5 (A)] synthetases has been hampered by the lack of an efficient expression
      system for a recombinant enzyme. Here, we report that the 9-2 isozyme of murine 2
      5 (A) synthetase can be efficiently expressed in insect cells using the
      baculovirus system. The recombinant protein was purified to apparent homogeneity,
      and its enzymatic activity was characterized. It had a high specific activity,
      required double-stranded RNA as a cofactor, and synthesized dimers to hexamers of
      2-5 (A). The utility of our expression system was demonstrated by studying the
      properties of two previously reported mutant proteins. Both of these mutants,
      when produced in bacteria, are enzymatically inactive, although similarly
      produced wild-type protein is active. Unexpectedly, when expressed in insect
      cells, both mutant proteins were enzymatically as active as the wild-type
      protein. These results suggest that in the eukaryotic expression system described
      here, the mutant proteins can undergo appropriate modifications or folding that
      is required for attaining an enzymatically active conformation.

PMID- 9521703
TI  - Mg2+ mediated sequence-specific binding of transcriptional activator protein C of
      bacteriophage Mu to DNA.
AB  - The contributions from the secondary structure of the transcriptional activator
      protein C of bacteriophage Mu to its specific DNA binding and the influence of
      various factors, viz., electrolytes, and minor groove and major groove binders on
      this protein-DNA interaction have been addressed. Circular dichroism (CD)
      spectral results suggest that, in the absence of Mg2+, C protein exhibits a beta
      pleated sheetlike structure and Mg2+ changes the conformation to a more alpha
      helical structure which could provide specific geometrical constraints
      complementary to those of DNA-helix. Thus, Mg2+ acts as a cofactor for the
      binding of the C protein to its specific site in DNA by inducing conformational
      changes in the protein. Competitive binding studies with minor and major groove
      binding drugs, viz., distamycin A and methyl green, respectively, and the DMS
      footprinting data indicate that the C protein recognizes the major groove of DNA
      during complex formation. Further, upon major groove binding, C protein brings
      about changes in DNA conformation; such conformational changes could have
      implications in the transcription process.

PMID- 9521704
TI  - Sequence specificity of a group II intron ribozyme: multiple mechanisms for
      promoting unusually high discrimination against mismatched targets.
AB  - Group II intron ai5 gamma was reconstructed into a multiple-turnover ribozyme
      that efficiently cleaves small oligonucleotide substrates in-trans. This
      construct makes it possible to investigate sequence specificity, since second
      order rate constants (kcat/K(m), or the specificity constant) can be obtained and
      compared with values for mutant substrates and with other ribozymes. The ribozyme
      used in this study consists of intron domains 1 and 3 connected in-cis, together
      with domain 5 as a separate catalytic cofactor. This ribozyme has mechanistic
      features similar to the first step of reverse-splicing, in which a lariat intron
      attacks exogenous RNA and DNA substrates, and it therefore serves as a model for
      the sequence specificity of group II intron mobility. To quantitatively evaluate
      the sequence specificity of this ribozyme, the WT kcat/Km value was compared to
      individual kcat/Km values for a series of mutant substrates and ribozymes
      containing single base changes, which were designed to create mismatches at
      varying positions along the two ribozyme-substrate recognition helices. These
      mismatches had remarkably large effects on the discrimination index (1/relative
      kcat/K(m)), resulting in values > 10,000 in several cases. The delta delta G++
      for mismatches ranged from 2 to 6 kcal/mol depending on the mismatch and its
      position. The high specificity of the ribozyme is attributable to effects on
      duplex stabilization (1-3 kcal/mol) and unexpectedly large effects on the
      chemical step of reaction (0.5-2.5 kcal/mol). In addition, substrate association
      is accompanied by an energetic penalty that lowers the overall binding energy
      between ribozyme and substrate, thereby causing the off-rate to be faster than
      the rate of catalysis and resulting in high specificity for the cleavage of long
      target sequences (> or = 13 nucleotides).

PMID- 9521705
TI  - Forskolin-induced dephosphorylation of the androgen receptor impairs ligand
      binding.
AB  - When androgen receptor containing cells are cultured in the presence of the PKA
      stimulator forskolin, a rapid dephosphorylation of the androgen receptor occurs
      resulting in a decrease in the amount of 112 kDa androgen receptor isoform and an
      increase in 110 kDa androgen receptor isoform on SDS-PAGE. To establish which
      amino acid residues in the androgen receptor were phosphorylated in control and
      forskolin-treated cells, trypsin-digested androgen receptors were subjected to RP
      HPLC analysis and subsequently to Edman degradation. It was observed that serine
      residues 506, 641, and 653 were potentially phosphorylated in control cells,
      while after forskolin treatment strong evidence was obtained that phosphorylation
      of serines 641 and 653 was significantly reduced. When the dephosphorylated
      androgen receptor was analyzed for its transcription activation capacity, it was
      observed that androgen-induced transcriptional regulation of two endogenous genes
      (PSA) and beta 1-subunit of Na,K-ATPase), in cells cultured in the presence of
      forskolin, was inhibited as compared to the control situation. The observation
      that the dephosphorylated androgen receptor was transcriptionally less active was
      further strengthened by the finding that the dephosphorylated androgen receptor
      was markedly impaired in ligand binding (Bmax was found to be reduced by
      approximately 40%). The current investigations show for the first time a clear
      function for the rapid phosphorylation which occurs directly after synthesis of
      the androgen receptor, namely, effective ligand binding.

PMID- 9521706
TI  - Labeling and identification of the postulated acid/base catalyst in the alpha
      glucosidase from Saccharomyces cerevisiae using a novel bromoketone C-glycoside.
AB  - alpha-Glucosidase from Saccharomyces cerevisiae is a member of a sequence-related
      family of alpha-glycosidases (family 13) that includes digestive alpha-amylases
      and commercially important cyclodextrin glucanotransferases. These enzymes
      catalyze the hydrolysis of alpha-linked oligosaccharides by a two-step mechanism
      involving a glycosyl-enzyme intermediate. A novel bromoketone C-glycoside
      inactivator, 1'-bromo-3'-(alpha-D-mannopyranosyl)-2'-propanone, has been
      synthesized and used to label the putative acid/base catalyst (Glu-276) of yeast
      alpha-glucosidase. Electrospray ionization mass spectrometry was used to
      demonstrate stoichiometric labeling of the protein. The labeled residue was
      identified by comparative liquid chromatographic/mass spectrometric analysis of
      peptic digests of labeled and unlabeled enzyme samples, which confirmed the
      unique presence of two labeled peptides of m/z 745 and 694. Subsequent tandem
      mass spectrometric analysis in the daughter-ion scan mode showed the two peptides
      to have an overlapping sequence in which Glu-276 was the labeled residue.
      Together with active-site-directed protection against inactivation with
      deoxynojirimycin, these results prove that Glu-276 is located within the active
      site of yeast alpha-glucosidase and, thus, provide further evidence for this
      residue playing an important role in catalysis.

PMID- 9521707
TI  - Reactions of alternate substrates demonstrate stereoelectronic control of
      reactivity in dialkylglycine decarboxylase.
AB  - Kinetic and product analyses of the reactions of dialkylglycine decarboxylase
      with several alternative substrates are presented. Rate constants for the
      reactions of amino and keto acids of several substrates decrease logarithmically
      with increasing side-chain size. Conversely, kcat for L-amino acid
      decarboxylation increases with side-chain size. These and other data confirm a
      proposed model for three binding subsites in the active site. In this model, bond
      making and breaking in both the decarboxylation and transamination half-reactions
      occurs at the "A" subsite, which maintains the scissile bond aligned with the p
      orbitals of the conjugated aldimine and thus maximizes stereoelectronic effects.
      This strongly supports the proposal by Dunathan (Proc. Natl. Acad. Sci. U.S.A.
      55, 712-716) that PLP-dependent enzymes can largely control reaction specificity
      by specific orientation about C alpha in the external aldimine intermediate. The
      "B" subsite can accept either an alkyl or a carboxylate group, while the "C"
      subsite accepts only small alkyl groups. This model predicts the existence of
      nonproductive binding modes for amino acids, which is proposed to be the ultimate
      origin of the kcat increase with side-chain size for L-amino acid
      decarboxylation. The specificity of the 2-aminoisobutyrate decarboxylation half
      reaction toward oxidative decarboxylation is very high (< 1 in 10(5) turnovers
      yields nonoxidative decarboxylation). The origin of this specificity is explored
      with the reactions of amino- and methylaminomalonate. These substrates exhibit
      high yields of nonoxidative decarboxylation, providing support for a model in
      which the interaction between a carboxylate group in the B subsite and Arg406 is
      a prerequisite to proton donation to and removal from C alpha.

PMID- 9521708
TI  - Pre-steady-state kinetic analysis of the reactions of alternate substrates with
      dialkylglycine decarboxylase.
AB  - The pre-steady-state kinetics of the half-reactions of several substrates with
      dialkylglycine decarboxylase are examined by multiwavelength kinetics and global
      analysis. The substrates examined fall into two groups: those that exhibit
      simple, monophasic kinetics and those that exhibit biphasic kinetics. The rate of
      the AIB half-reaction is likely limited by the decarboxylation step based on the
      simple kinetics and spectra obtained from global analysis. The spectra for the
      first species in the transamination half-reactions of L-alanine and L
      aminobutyrate show long-wavelength absorption characteristic of a carbanionic
      quinonoid intermediate. This demonstrates that formation of the external aldimine
      intermediates and abstraction of the C alpha protons from them are rapid. The
      reactions of the slower substrates L-phenylglycine and 1-aminocyclohexane-1
      carboxylate may have external aldimine formation as the rate-determining step.
      The biphasic reactions of 2-methyl-2-aminomalonate, 1-aminocyclopentane-1
      carboxylate, isopropylamine, and glycine all have external aldimine formation as
      the rapid observable step, based on the spectral changes observed in absorption
      and circular dichroism measurements. 2-Methyl-2-aminomalonate reacts
      approximately 10(4)-fold slower than does AIB with dialkylglycine decarboxylase,
      compared to approximately 10(5)-fold faster with coenzyme in solution. It is
      proposed that this radical reactivity reversal is due to a slow protein
      conformational change that is a prerequisite to decarboxylation of MAM, which
      occurs rapidly thereafter. Circular dichroism measurements on active site bound
      coenzyme provide evidence supporting this proposal. The binding of the
      noncovalent inhibitors pyruvate or lactate or the covalently binding inhibitor 1
      aminocyclopropane-1-carboxylate all induce a slow change in coenzyme circular
      dichroism that quantitatively parallels the slow decarboxylation of 2-methyl-2
      aminomalonate. Fast circular dichroism changes are seen in the mixing time of
      these measurements for both 1-aminocyclopropane-1-carboxylate and 2-methyl-2
      aminomalonate, indicating rapid external aldimine formation on this longer time
      scale.

PMID- 9521709
TI  - Regulating energy transfer in the ATP sulfurylase-GTPase system.
AB  - ATP sulfurylase, isolated from Escherichia coli K-12, is a GTPase-target complex
      that catalyzes and links the energetics of GTP hydrolysis to the synthesis of
      activated sulfate (APS). When the GTP concentration is saturating and held fixed
      with a regenerating system, the APS reaction reaches a steady state in which its
      mass ratio is shifted (5.4 x 10(6))-fold toward the product by the hydrolysis of
      GTP. If GTP is not regenerated, the shift toward the product is transient,
      producing a pulse-shaped progress curve. The mechanistic basis of this transience
      is the subject of this paper. The product transient is caused by the binding of
      GDP to the enzyme which establishes a catalytic pathway that allows the chemical
      potential that had been transferred to the APS reaction to "leak" into the
      chemical milieu. The system leaks because the E.GDP complex catalyzes the
      uncoupled APS reaction. The addition of phosphate to the leaky GDP.E.APS.PPi
      complex converts it into the central Pi.GDP.E.APS.PPi complex which catalyzes the
      energy-transfer reaction. Thus, Pi binding directs the system through the coupled
      mechanism, "plugging" the leak. GMPPNP, which also causes a leak, is used to
      demonstrate that the mass ratio of the APS reaction can be "tuned" by adjusting
      flux through the coupled and uncoupled pathways. This energy-coupling mechanism
      provides a means for controlling the quantity of chemical potential transferred
      to the APS reaction. This versatile linkage might well be used to the cell's
      advantage to avoid the toxicity associated with an excess of activated sulfate.

PMID- 9521710
TI  - Inhibitor and NAD+ binding to poly(ADP-ribose) polymerase as derived from crystal
      structures and homology modeling.
AB  - Inhibitors of poly(ADP-ribose) polymerase (PARP, EC 2.4.2.30) are of clinical
      interest because they have potential for improving radiation therapy and
      chemotherapy of cancer. The refined binding structures of four such inhibitors
      are reported together with the refined structure of the unligated catalytic
      fragment of the enzyme. Following their design, all inhibitors bind at the
      position of the nicotinamide moiety of the substrate NAD+. The observed binding
      mode suggests inhibitor improvements that avoid other NAD(+)-binding enzymes.
      Because the binding pocket of NAD+ has been strongly conserved during evolution,
      the homology with ADP-ribosylating bacterial toxins could be used to extend the
      bound nicotinamide, which is marked by the inhibitors, to the full NAD+ molecule.

PMID- 9521711
TI  - Effect of single chain lipids on phospholipase C-promoted vesicle fusion. A test
      for the stalk hypothesis of membrane fusion.
AB  - The effect of low proportions (up to 5 mol %) of single-chain lipids on
      phospholipase C-promoted fusion of large unilamellar vesicles has been
      investigated with the aim of testing the so-called stalk model of membrane
      fusion. This model is known in two main versions, the one originally published by
      Kozlov and Markin [Kozlov, M. M. and Markin, V. S. (1983) Biofizika 28, 255-261]
      and what is known as the "modified stalk model" [Siegel, D. P. (1993) Biophys. J.
      65, 2124-2140], that differ in a number of predictions. In the view of the latter
      author, hydrocarbons or other nonpolar lipids should help fusion by decreasing
      the interstitial energy of the stalk connecting the two apposed bilayers. We show
      that small amounts of hexadecane or squalene increase significantly the fusion
      rates in our system. Changes in monolayer curvature are the object of different
      predictions by the original and modified stalk theories. According to the
      original form, fusion would be promoted by lipids inducing a negative curvature
      in the closest (cis) monolayers of the fusing membranes and inhibited by the same
      lipids in the trans monolayers; the opposite would happen with lipids inducing a
      positive curvature. The modified stalk model predicts that fusion is helped by
      increasing the negative curvature of both monolayers. In our system,
      symmetrically distributed arachidonic acid, which increases the negative
      curvature, enhances lipid and content mixing, and the opposite is found with
      symmetrically distributed lysophosphatidylcholine or palmitoylcarnitine, which
      facilitate a positive monolayer curvature. In addition, fluorescence polarization
      and 31P NMR studies of the lamellar-to-isotropic (Q224 cubic) thermotropic
      transition of a lipid mixture corresponding to our liposomal composition reveal
      that all lipids that facilitate fusion decrease the transition temperature, while
      fusion inhibitors increase the transition temperature. Moreover, fusion (content
      mixing) rates show a maximum at the lamellar-to-isotropic transition temperature.
      These observations support the involvement of inverted lipid structures, as
      occurring in the inverted cubic phases, in membrane fusion. All these data are in
      full agreement with the stalk model of membrane fusion, particularly in its
      modified version.

PMID- 9521712
TI  - Magainin 2 amide interaction with lipid membranes: calorimetric detection of
      peptide binding and pore formation.
AB  - The interaction of the antibiotic magainin 2 amide (M2a) with lipid bilayers was
      investigated with high-sensitivity titration calorimetry. The enthalpy of
      transfer of the cationic M2a to negatively charged small unilamellar vesicles
      composed of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and 1
      palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol (POPG) (75:25, mol/mol) was
      measured as delta H = -17.0 +/- 1 kcal/mol of peptide. The adsorption isotherm
      was determined by injecting lipid vesicles into peptide solutions at low peptide
      concentrations (cPo < 7 microM). The apparent partition coefficient was Kapp
      approximately 1.2 x 10(4) M-1 at a peptide equilibrium concentration of 1 microM
      but decreased with increasing peptide concentration. The hydrophobic partitioning
      of M2a into the lipid membrane is modulated by electrostatic effects that arise
      from the attraction of the positively charged peptide to the negatively charged
      membrane. Using the Gouy-Chapman theory to correct for electrostatic attraction,
      the experimental binding isotherms can be explained with an intrinsic
      (hydrophobic) partition coefficient of K = 55 +/- 5 M-1 and an effective peptide
      charge of z = 3.7-3.8. The free energy of binding is delta G = -4.8 kcal/mol. At
      peptide concentrations cPo > approximately 7 microM, a second effect comes into
      play, and the titration enthalpies can no longer be explained exclusively by
      peptide partitioning. The first few injections produce enthalpies of reaction
      which are distinctly smaller than expected from a pure partition equilibrium,
      followed by a series of injections with reaction heats larger than expected.
      After subtracting the enthalpic contribution due to partitioning, the residual
      enthalpies are endothermic for the first few injections, and exothermic for the
      consecutive steps. Furthermore, the endothermic excess heat is compensated
      exactly by the exothermic excess heat; i.e., the excess heat consumed in the
      first part of the titration experiment is returned during the second part.
      Endothermic excess enthalpies are observed for total molar peptide-to-lipid
      ratios of P/L > approximately 3.0%, whereas exothermic excess heats were seen for
      0.7% < P/L < 3.0%. Below P/L < approximately 0.7%, the binding follows the
      partition equilibrium. Based on earlier spectroscopic evidence, it is suggested
      that magainin 2 amide binds to the lipid membrane and forms pores at high peptide
      to-lipid ratio, this process being characterized by an endothermic reaction
      enthalpy. Pore formation is reversed with increasing lipid concentration, and the
      peptide pores disintegrate. The limiting peptide-to-lipid ratio deduced from
      titration calorimetry for M2a pore formation is in excellent agreement with
      spectroscopic methods. The enthalpy of pore formation amounts to delta H = +6.2
      +/- 1.6 kcal/mol peptide or delta H approximately 25-45 kcal/mol pore if the pore
      is comprised of 4-7 peptide molecules.

PMID- 9521713
TI  - Identification of novel in vitro PKA phosphorylation sites on the low and middle
      molecular mass neurofilament subunits by mass spectrometry.
AB  - Phosphorylation of the head domains of intermediate filament proteins by second
      messenger-dependent kinases is important in regulating filament assembly. In the
      case of neurofilaments, head domain phosphorylation is known to be important in
      assembly, but few sites have been identified. Using matrix-assisted laser
      desorption-ionization (MALDI) and nano-electrospray mass spectrometry, we report
      the identification of several novel in vitro cAMP-dependent protein kinase (PKA)
      phosphorylation sites in the low (NF-L) and middle (NF-M) molecular mass
      neurofilament subunits. Neurofilament polypeptides were purified from adult rat
      brain, and fractions containing a mixture of NF-L and NF-M were
      nonradioisotopically phosphorylated with PKA prior to proteolytic digestion of
      the polypeptides in situ in polyacrylamide excised from SDS gels. Sites of
      phosphorylation were determined by mass spectrometric analysis of mixtures
      enriched in tryptic phosphopeptides. In NF-L, four novel sites were identified:
      serines 12, 41, and 49 in the head domain and serine 435 in the carboxyl-terminal
      tail domain, and data consistent with phosphorylation of serine 2 were obtained.
      Recombinant rat NF-L protein was also phosphorylated with PKA, and the same
      serines were identified as phosphorylation sites, with two additional sites,
      serine 43 and probable phosphorylation of serine 55. In NF-M, one novel site,
      serine 1 in the amino-terminal head domain, was found to be phosphorylated, and
      serine 46, also in the amino-terminal head domain, was confirmed as a PKA
      phosphorylation site.

PMID- 9521714
TI  - Characterization of the phosphorylation sites of human high molecular weight
      neurofilament protein by electrospray ionization tandem mass spectrometry and
      database searching.
AB  - Hyperphosphorylated high molecular weight neurofilament protein (NF-H) exhibits
      extensive phosphorylation on lysine-serine-proline (KSP) repeats in the C
      terminal domain of the molecule. Specific phosphorylation sites in human NF-H
      were identified by proteolytic digestion and analysis of the resulting digests by
      a combination of microbore liquid chromatography, electrospray ionization tandem
      (MS/MS) ion trap mass spectrometry, and database searching. The computer programs
      utilized (PEPSEARCH and SEQUEST) are capable of identifying peptides and
      phosphorylation sites from uninterpreted MS/MS spectra, and by use of these
      methods, 27 phosphopeptides and their phosphorylated residues were identified. On
      the basis of these phosphopeptides, 38 phosphorylation sites in human NF-H were
      characterized. These include 33 KSP, lysine-threonine-proline (KTP) or arginine
      serine-proline (RSP) sites and four unphosphorylated sites, all of which occur in
      the KSP repeat domain (residues 502-823); and one threonine phosphorylation site
      observed in a KVPTPEK motif. Six KSP sites were not characterized because of the
      failure to isolate and identify corresponding phosphopeptides. Heterogeneity in
      serine and threonine phosphorylation was observed at three sites or deduced to
      occur at three sites on the basis of enzyme specificity. As a result of the
      phosphorylated motifs identified (KSPAKEE, KSPVKEE, KS/TPEKAK, KSPEKEE, KSPVKAE,
      KSPAEAK, KSPPEAK, KSPEAKT, KSPAEVK, and KVPTPEK), human NF-H tail domain is
      postulated to be a substrate of proline-directed kinases. The threonine
      phosphorylated KVPTPEK motif suggested the existence of a novel proline-directed
      kinase.

PMID- 9521716
TI  - Demonstration of covalent binding of lipoprotein(a) [Lp(a)] to fibrin and
      endothelial cells.
AB  - It has been well documented that Lp(a) binds noncovalently to fibrin or human
      umbilical vein endothelial cells. This binding is to lysines and is inhibited by
      lysine analogues such as epsilon-aminocaproic acid (EACA). In the present study,
      Lp(a) (0.006-0.6 microM) binding to immobilized fibrin and endothelial cells was
      evaluated by ELISA with an anti-Lp(a) antibody. A significant portion
      (approximately 65%) of the Lp(a) was found to resist dissociation by EACA (0.2
      M). The EACA resistant binding of Lp(a) was time and concentration dependent. The
      addition of EDTA to the incubation mixture had no effect, thereby excluding cross
      linking by transglutaminase as a mechanism. This portion of Lp(a) was also
      resistant to dissociation by acid (0.1 N HCl), 0.1% SDS, 1 M benzamidine, Tris
      HCl (1 M, pH 12), or DTT (5 mM), but it was washed off by 0.1 N NaOH (which did
      not remove the immobilized fibrin). This suggested that the Lp(a) was covalently
      linked by an ester bond. Covalent binding was inhibited when Lp(a) was mildly
      oxidized by BioRad Enzymobeads, which may explain why it escaped recognition in
      experiments with radiolabeled Lp(a). Covalent binding was attenuated when Lp(a)
      was pretreated with DFP suggesting that the serine residue in the pseudo active
      site of Lp(a) was involved. Lp(a) also bound covalently to immobilized BSA,
      indicating some nonspecificity. However, binding to BSA was almost 3-fold less
      than to fibrin, suggesting that lysine binding may facilitate covalent binding. A
      similar proportion of EACA resistant binding of Lp(a) was found with endothelial
      cells. In conclusion, the findings demonstrate a novel, covalent binding by Lp(a)
      which is kringle independent and is postulated to involve the pseudo protease
      domain of Lp(a). This property may contribute to the deposition of Lp(a) on
      endothelial surfaces and its colocalization with fibrin in atheromas.

PMID- 9521717
TI  - Binding of actinomycin D to DNA oligomers of CXG trinucleotide repeats.
AB  - Actinomycin D (ACTD) binding propensities of DNA with CXG trinucleotide repeats
      were investigated using oligomers of the form d[AT(CXG)n = 2-4AT] and their
      corresponding heteroduplexes, where X = A, C, G, or T. These oligonucleotides
      contain -CXGCXG-, -CXGCXGCXG-, and -CXGCXGCXGCXG- units that can form
      homoduplexes containing one, two, and three GpC binding sites, respectively, with
      flanking X/X mismatches. The corresponding heteroduplexes contain these same
      sites with flanking Watson-Crick base pairs. It was found that oligomers with X =
      G exhibit weak ACTD affinities whereas those with X not equal to G and n = 3
      exhibit unusually strong ACTD binding affinities with binding constants ranging
      from 2.3 x 10(7) to 3.3 x 10(7) M-1 and binding densities of approximately 1 drug
      molecule/strand (or 2/duplex). These binding affinities are considerably higher
      than those of their shorter and longer counterparts and are about 2- and 10-fold
      stronger than the corresponding CAG.CTG and CGG.CCG heteroduplexes, respectively.
      The CTG-containing oligomer d[AT(CTG)3AT] stands out as unique in having its ACTD
      dissociation kinetics being dominated by a strikingly slow process with a
      characteristic time of 205 min at 20 degrees C, which is 100-fold slower than
      d[AT(CAG)3AT], nearly 10-fold slower than the corresponding heteroduplex, and
      considerably slower than d[AT(CTG)2AT] (63 min) and d[AT(CTG)4AT] (16 min). The
      faster dissociation rate of the n = 4 oligomer compared to its n = 2 counterpart
      is in apparent contrast with the observed 10-fold stronger ACTD binding affinity
      of the former. It was also found that d[AT(CCG)3AT] exhibits the slowest
      dissociation rate of the CGG/CCG series, being more than an order of magnitude
      slower than that of its heteroduplex (tau slow of 43 vs 2 min). The finding that
      a homoduplex d[AT-CXG-CXG-CXG-AT]2 can bind two ACTD molecules tightly is
      significant since it was thought unlikely for two consecutive GpC sites separated
      by a single T/T mismatch to do so.

PMID- 9521715
TI  - Identification of residues lining the anthrax protective antigen channel.
AB  - In its activated 63 kDa form, the protective antigen (PA) component of anthrax
      toxin forms a heptameric prepore, which converts to a pore (channel) in endosomal
      membranes at low pH and mediates translocation of the toxin's enzymic moieties to
      the cytosol. It has been proposed that the prepore-to-pore conversion involves a
      conformational rearrangement of a disordered amphipathic loop (D2L2; residues 302
      325), in which loops from the 7 protomers combine to form a transmembrane 14
      stranded beta barrel. To test this model, we generated Cys substitutions in 24
      consecutive residues of the D2L2 loop, formed channels in artificial bilayers
      with each mutant, and examined changes in channel conductance after adding the
      thiol-reactive, bilayer-impermeant reagent methanethiosulfonate
      ethyltrimethylammonium (MTS-ET) to the trans compartment. The rationale for these
      experiments is that reaction of MTS-ET with a Cys residue adds a positively
      charged group and therefore would likely reduce channel conductance if the
      residue were in the ion-conducting pathway. We found alternating reduction and
      absence of reduction of conductance in consecutive residues over two stretches
      (residues 302-311 and 316-325). This pattern is consistent with alternating polar
      and apolar residues of the two stretches projecting into the pore lumen and into
      the bilayer, respectively. Residues connecting these two stretches (residues 312
      315) were responsive to MTS-ET, consistent with their being in a turn region.
      Single channels formed by selected mutants (H304C and N306C) showed multiple
      conductance step changes in response to MTS-ET, consistent with an oligomeric
      pore. We also found that the binding site for the channel-blocking
      tetraalkylammonium ions is located cis relative to the inserted D2L2 loops. These
      findings constitute strong evidence in favor of the model of conversion of the
      prepore to a 14-stranded beta barrel pore and solidify the foundation for studies
      to understand the mechanism of translocation by anthrax toxin.

PMID- 9521718
TI  - Evidence for oxidation-state-dependent conformational changes in human ferredoxin
      from multinuclear, multidimensional NMR spectroscopy.
AB  - Human ferredoxin belongs to the vertebrate ferredoxin family which includes
      bovine adrenodoxin. It is a small (13.8 kDa) acidic protein with a [2Fe-2S]
      cluster. It functions as an electron shuttle in the cholesterol side-chain
      cleavage reaction which is the first step of steroid hormone biosynthesis. The
      protein studied here was produced in Escherichia coli and doubly labeled with 13C
      and 15N. The diamagnetic 15N, 13C', 13C alpha, 13C beta, 1H alpha, and 1HN
      resonances from about 70% of the 124 amino acid residues for oxidized human
      ferredoxin and 80% of those for the reduced protein have been assigned primarily
      on the basis of results from three-dimensional, triple-resonance experiments.
      Secondary structure features for human ferredoxin in its oxidized and reduced
      states have been identified from a combination of chemical shift index and NOE
      data. Comparison of NMR results from the protein in its oxidized and reduced
      states indicates that structural changes accompany the change in the oxidation
      state of the [2Fe-2S] cluster. Major differences are localized at two regions:
      residues 29-31 and residues 109-124; the latter stretch forms the C-terminal
      region of the protein. The possible functional significance of these oxidation
      state-dependent structural changes is discussed.

PMID- 9521719
TI  - Proton/hydrogen transfer affects the S-state-dependent microsecond phases of
      P680+ reduction during water splitting.
AB  - To investigate a possible coupling between P680+ reduction and hydrogen transfer,
      we studied the effects of H2O/D2O exchange on the P680+ reduction kinetics in the
      nano- and microsecond domains. We concentrated on studying the period-4
      oscillatory (i.e., S-state-related) part of the reduction kinetics, by analyzing
      the differences between the P680+ reduction curves, rather than the full
      kinetics. Earlier observations that P680+ reduction kinetics have microsecond
      components were confirmed: the longest observable lifetime whose amplitude showed
      period-4 oscillations was 30 microseconds. We found that solvent isotope exchange
      left the nanosecond phases of the P680+ reduction unaltered. However, a
      significant effect on the oscillatory microsecond components was observed. We
      propose that, at least in the S0/S1 and S3/S0 transitions, hydrogen (proton)
      transfer provides an additional decrease in the free energy of the YZ+P680 state
      with respect to the YZP680+ state. This implies that relaxation of the state
      YZ+P680 is required for complete reduction of P680+ and for efficient water
      splitting. The kinetics of the P680+ reduction suggest that it is intraprotein
      proton/hydrogen rearrangement/transfer, rather than proton release to the bulk,
      which is occurring on the 1-30 microseconds time scale.

PMID- 9521720
TI  - Local-access model for proton transfer in bacteriorhodopsin.
AB  - The accessibility of the retinal Schiff base in bacteriorhodopsin was studied in
      the D85N/D96N mutant where the proton acceptor and donor are absent. Protonation
      and deprotonation of the Schiff base after pH jump without illumination and in
      the photocycle of the unprotonated Schiff base were measured in the visible and
      the infrared. Whether access is extracellular (EC) or cytoplasmic (CP) was
      decided from the effect of millimolar concentrations of azide on the rates of
      proton transfers. The results, together with earlier work on the wild-type
      protein, suggest a new hypothesis for the proton-transfer switch: (i) In the
      metastable 13-cis, 15-anti and all-trans, 15-syn photoproducts, but not in the
      stable isomeric states, access flickers between the EC and CP directions. (ii)
      The direction of proton transfer is decided both by this local access and by the
      presence of a suitable donor or acceptor group (in the wild type), or the proton
      conductivity in the EC and CP half-channels (in D85N/D96N). (iii) Thermal
      reisomerization of the retinal can occur only when the Schiff base is protonated,
      as is well-known. In the wild-type transport cycle, the concurrent local EC and
      CP access during the lifetime of the metastable 13-cis, 15-anti state enables the
      changing pKa's of the proton acceptor and donor to determine the direction of
      proton transfer. Proton transfer from the Schiff base to Asp-85 in the EC
      direction is followed by reprotonation by Asp-96 from the CP direction because
      proton release to the EC surface raises the pKa of Asp-85 and a large-scale
      protein conformation change lowers the pKa of Asp-96. The unexpected finding we
      report here for D85N/D96N, that when the retinal is in the stable all-trans, 15
      anti and 13-cis, 15-syn isomeric forms access of the Schiff base is locked (in
      the EC and CP directions, respectively), suggests that in this protein
      reisomerization, rather than changes in the proton conductivities of the EC and
      CP half-channels, provides the switch function. With this mechanism, the various
      modes of transport reported for Asp-85 mutants (CP to EC direction with blue
      light, and EC to CP direction with blue plus green light) are understood also in
      terms of rules i-iii.

PMID- 9521721
TI  - The MCD and EPR of the heme centers of nitric oxide reductase from Pseudomonas
      stutzeri: evidence that the enzyme is structurally related to the heme-copper
      oxidases.
AB  - EPR spectra at liquid helium temperatures and MCD spectra at room temperature and
      4.2 K are presented for fully oxidized nitric oxide reductase (NOR) from
      Pseudomonas stutzeri. The MCD spectra show that the enzyme contains three heme
      groups at equivalent concentrations but distinctive in their axial coordination.
      Two, in the low-spin ferric state at all temperatures, give rise to infrared
      charge-transfer transitions which show the hemes to have bis-histidine and
      histidine-methionine ligation, respectively. The EPR spectra show them to be
      magnetically isolated. The third heme has an unusual temperature-dependent spin
      state and spectroscopic features which are consistent with histidine-hydroxide
      coordination. No EPR signals have been detected from this heme. Together with its
      unusual near-infrared MCD, this suggests a spin-spin interaction between this
      heme and another paramagnet. The three hemes account for only 75% of the iron
      content, and it is concluded that the additional paramagnet is a mononuclear
      ferric ion. These results provide further evidence that NOR is indeed
      structurally related to heme-copper oxidases and that it contains a heme/non-heme
      iron spin-coupled pair at the active site.

PMID- 9521722
TI  - Origin of dimeric structure in the ribonuclease superfamily.
AB  - To enable application of postgenomic evolutionary approaches to understand the
      divergence of behavior and function in ribonucleases (RNases), the impact of
      divergent sequence on the divergence of tertiary and quaternary structure is
      analyzed in bovine pancreatic and seminal ribonucleases, which differ by 23 amino
      acids. In a crystal, seminal RNase is a homodimer joined by two "antiparallel"
      intersubunit disulfide bonds between Cys-31 from one subunit and Cys-32' from the
      other and having composite active sites arising from the "swap" of residues 1-20
      from each subunit. Specialized Edman degradation techniques have completed the
      structural characterization of the dimer in solution, new cross-linking methods
      have been developed to assess the swap, and sequence determinants of quaternary
      structure have been explored by protein engineering using the reconstructed
      evolutionary history of the protein family as a guide. A single Cys at either
      position 32 (the first to be introduced during the divergent evolution of the
      family) or 31 converts monomeric RNase A into a dimer. Even with an additional
      Phe at position 31, another residue introduced early in the seminal lineage, swap
      is minimal. A hydrophobic contact formed by Leu-28, however, also introduced
      early in the seminal lineage, increases the amount of "antiparallel" connectivity
      of the two subunits and facilitates swapping of residues 1-20. Efficient swapping
      requires addition of a Pro at position 19, a residue also introduced early in the
      divergent evolution of the seminal RNase gene. Additional cysteines required for
      dimer formation are found to slow refolding of the protein through formation of
      incorrect disulfide bonds, suggesting a paradox in the biosynthesis of the
      protein. Further studies showed that the dimeric form of seminal RNase known in
      the crystal is not the only form in vivo, where a substantial amount of
      heterodimer is known. These data complete the acquisition of the background
      needed to understand the evolution of new structure, behavior, and function in
      the seminal RNase family of proteins.

PMID- 9521723
TI  - Origin of the catalytic activity of bovine seminal ribonuclease against double
      stranded RNA.
AB  - Bovine seminal ribonuclease (RNase) binds, melts, and (in the case of RNA)
      catalyzes the hydrolysis of double-stranded nucleic acid 30-fold better under
      physiological conditions than its pancreatic homologue, the well-known RNase A.
      Reported here are site-directed mutagenesis experiments that identify the
      sequence determinants of this enhanced catalytic activity. These experiments have
      been guided in part by experimental reconstructions of ancestral RNases from
      extinct organisms that were intermediates in the evolution of the RNase
      superfamily. It is shown that the enhanced interactions between bovine seminal
      RNase and double-stranded nucleic acid do not arise from the increased number of
      basic residues carried by the seminal enzyme. Rather, a combination of a dimeric
      structure and the introduction of two glycine residues at positions 38 and 111 on
      the periphery of the active site confers the full catalytic activity of bovine
      seminal RNase against duplex RNA. A structural model is presented to explain
      these data, the use of evolutionary reconstructions to guide protein engineering
      experiments is discussed, and a new variant of RNase A, A(Q28L K31C S32C D38G
      E111G), which contains all of the elements identified in these experiments as
      being important for duplex activity, is prepared. This is the most powerful
      catalyst within this subfamily yet observed, some 46-fold more active against
      duplex RNA than RNase A.

PMID- 9521724
TI  - Structural variation induced by different nucleotides at the cleavage site of the
      hammerhead ribozyme.
AB  - The hammerhead ribozyme is capable of cleaving RNA substrates at 5' UX 3'
      sequences (where the cleavage site, X, can be A, C, or U). Hammerhead complexes
      containing dC, dA, dI, or rG nucleotides at the cleavage site have been studied
      by NMR. The rG at the cleavage site forms a Watson-Crick base pair with C3 in the
      conserved core of the hammerhead, indicating that rG substrates inhibit the
      cleavage reaction by stabilizing an inactive conformation of the molecule.
      Isotope-edited NMR experiments on the hammerhead complexes show that there are
      different short proton-proton distances between neighboring residues depending
      upon whether there is a dC or dA at the cleavage site. These NMR data demonstrate
      that there are significant differences in the structure and/or dynamics of the
      active-site residues in these hammerhead complexes. Molecular dynamics
      calculations were used to model the conformations of the cleavage-site variants
      consistent with the NMR data. The solution conformations of the hammerhead
      ribozyme-substrate complexes are compared with the X-ray structure of the
      hammerhead ribozyme and are used to help understand the thermodynamic and kinetic
      differences among the cleavage-site variants.

PMID- 9521725
TI  - Steady-state kinetics of the hypoxanthine-guanine-xanthine
      phosphoribosyltransferase from Tritrichomonas foetus: the role of threonine-47.
AB  - Tritrichomonas foetus, an anaerobic flagellated protozoan, causes urogenital
      trichomoniasis in cattle. Hypoxanthine-guanine-xanthine phosphoribosyl
      transferase (HGXPRTase), an essential enzyme in T. foetus required for salvaging
      exogenous purine bases, has been regarded as a promising target for anti
      tritrichomonial chemotherapy. The steady-state kinetic analyses of synthesis and
      pyrophosphorolysis of IMP, GMP, and XMP and product inhibition studies have been
      used to elucidate the reaction mechanisms. Double-reciprocal plots of initial
      velocities versus the varying concentrations of one substrate at a fixed
      concentration of the other show intersecting lines indicating a sequential
      mechanism for both the forward and the reverse reactions. In terms of the kcat/Km
      ratios, hypoxanthine is the most effective substrate whereas guanine and xanthine
      are converted equally well into their corresponding nucleotides. The minimum
      kinetic model from the data in product inhibition studies is an ordered bi-bi
      mechanism, where the substrates bind to the enzyme (first PRPP followed by the
      purine bases), and the products released (first PPi followed by purine
      nucleotide) in a defined order. The Kms for PPi in the T. foetus HGXPRTase
      catalyzed reactions are unusually high, close to the millimolar range. Since the
      crystal structure of this enzyme [Somoza et al. (1996) Biochemistry 35, 7032
      7040] suggests potential binding between the threonine-47 in a conserved cis
      peptide loop and PPi whereas human HGPRTase has lysine-68 [Eads et al. (1994)
      Cell 78, 325-334] at the corresponding position, we prepared a T47K enzyme mutant
      and found in the T47K-catalyzed reaction a 4-10-fold decrease of Km for PPi. The
      lack of ionic interactions between Thr-47 and PPi and an increased distance
      between the loop and the active site as compared to the human HGPRTase are thus
      proposed to be responsible for the high Km for PPi in the T. foetus HGXPRTase
      catalyzed reaction.

PMID- 9521726
TI  - Structure/function relationships of a G-protein coupling pocket formed by the
      third intracellular loop of the m5 muscarinic receptor.
AB  - Using random saturation mutagenesis, we have previously identified the amino
      acids K439, A440, and A441 in the C-terminus of the third intracellular loop
      (Ci3) of the m5 muscarinic receptor as being critical for G-protein coupling
      [Burstein, E. S., Spalding, T. A., Hill-Eubanks, D., and Brann, M. R. (1995) J.
      Biol. Chem. 270, 3141-3146]. In the present study, we have constructed a series
      of point mutants at each of these residues and characterized their functional
      phenotypes in order to define the structure/function relationships of each of
      these residues for G-protein coupling. Although a wide variety of substitutions
      were tolerated at K439, most caused significant increases in the EC50 of
      carbachol and decreases in the maximum response (Rmax). Only other basic residues
      were well tolerated (<10-fold increase in EC50, >70% of wild type). Acidic
      substitutions had the largest effects, reducing Rmax to under 20% of wild type.
      At A440, only the conservative substitution threonine was well tolerated.
      Substitutions by hydrophobic, polar, and basic residues caused 10-80-fold
      increases in EC50 values and in many cases also significantly reduced Rmax (<70%
      of wild type). In contrast, at A441 mutations selectively affected EC50 but not
      Rmax values. Previously we identified I216, Y217, T220, and R223 as the residues
      in the N-terminus of the i3 loop of m5 (Ni3) that are critical for G-protein
      coupling [Burstein, E. S., Spalding, T. S., and Brann, M. R. (1996) J. Biol.
      Chem. 271, 2882-2885]. To investigate whether there were additive contributions
      of Ni3 and Ci3 to G-protein coupling, the functional responses of two double
      mutants, R223E/K439E and Y217S/A441T, were evaluated. Though these mutations were
      tolerated individually, both double mutant receptors produced almost indetectable
      responses. Little or no changes in expression levels or ligand binding properties
      were detected, suggesting the observed effects were caused primarily by changes
      receptor/G-protein coupling. We conclude that K439 participates in G-protein
      activation through an ionic mechanism, that A440 fulfills a structural role
      forming part of the G-protein coupling pocket, and that A441 contributes to
      receptor affinity for G-proteins. We propose that the third intracellular loop
      forms a G-protein coupling pocket comprised of a positively charged "lip" and a
      hydrophobic core.

PMID- 9521727
TI  - Conformations of nicked and gapped DNA structures by NMR and molecular dynamic
      simulations in water.
AB  - We have analyzed and compared the molecular structures and dynamics of DNA
      duplexes containing a nick or a gap of one nucleotide where the base in front of
      the gap is a guanine. The continuous strand has the sequence 5'(CAGAGTCXCTGGCTC)
      where the residue X is absent for the nick, 14-mer, and where it is a G residue
      for the gap. Duplexes were formed with the two corresponding 7-mers. Neither of
      these is phosphorylated adjacent at the nick site, but it is a good model for a
      single strand break. For the nick structure, the quantitative NMR data show that
      the global conformation is very close to canonical B-form DNA, but it displays
      enhanced local flexibility. For the gap structure, we observe only one species in
      which the extra G is well stacked into the helix. The two half-helices around
      this residue also show a B-form conformation. As with the nick duplex, the
      adjacent G imino protons show enhanced exchange with solvent. The gap does not
      close completely. Using distance constraints, MD calculations show that the nick
      conformation is very close to a duplex with no lesion but is indeed more flexible
      in the central part. The gapped structure shows two families of conformations.
      One is close to B-DNA, the other is significantly kinked at the gap which reduces
      the size of the cavity. We observe a spine of hydration within the cavities,
      similar, but of different geometry in the two cases.

PMID- 9521728
TI  - Structural basis for different inhibitory specificities of human cystatins C and
      D.
AB  - Human cystatins C and D share almost identical primary structures of two out of
      the three segments proposed to be of importance for enzyme interactions but have
      markedly different profiles for inhibition of the target cysteine peptidases,
      cathepsins B, H, L, and S. To investigate if the N-terminal binding regions of
      the inhibitors are responsible for the different inhibition profiles, and thereby
      confer biological selectivity, two hybrid cystatins were produced in Escherichia
      coli expression systems. In one hybrid, the N-terminal segment of cystatin C was
      placed on the framework of cystatin D, and the second was engineered with the N
      terminal segment of cystatin D on the cystatin C scaffold. Truncated cystatin C
      and D variants, devoid of their N-terminal segments, were obtained by incubation
      with glycyl endopeptidase and isolated, in a second approach to assess the
      importance of the N-terminal binding regions for cystatin function and
      specificity. The affinities of the four cystatin variants for cathepsins B, H, L,
      and S were measured. By comparison with corresponding results for wild-type
      cystatins C and D, it was concluded (1) that both the N-terminal and framework
      part of the molecules significantly contribute to the observed differences in
      inhibitory activities of cystatins C and D and (2) that the N-terminal segment of
      cystatin C increases the inhibitory activity of cystatin D against cathepsin S
      and cathepsin L but results in decreased activity against cathepsin H. These
      differences in specificity were explained by the residues interacting with the S2
      subsite of peptidases (Val- and Ala-10 in cystatin C and D, respectively). Also,
      removal of the N-terminal segment results in total loss of enzyme affinity for
      cystatin D but not for cystatin C. Therefore, structural differences in the
      framework parts, as well as in the N-terminal segments, are critical for both
      inhibitory specificity and potency. Homology modeling was used to identify
      residues likely responsible for the generally reduced inhibitory potency of
      cystatin D.

PMID- 9521729
TI  - The ice-binding site of Atlantic herring antifreeze protein corresponds to the
      carbohydrate-binding site of C-type lectins.
AB  - The type II antifreeze proteins (AFPs) of smelt and Atlantic herring are
      homologous to the carbohydrate-recognition domains (CRDs) of Ca2+-dependent (C
      type) animal lectins and, like these lectins, acquire a stable and active
      structure upon binding Ca2+ ions. In the C-type lectin CRD, the carbohydrate
      binding site is located at a Ca2+-binding site. Site-directed mutagenesis was
      used to test the hypothesis that the ice-binding site of the type II AFP
      corresponds to the carbohydrate-binding site of the lectins. To disrupt this site
      in the herring AFP without perturbing the Ca2+-dependent protein fold, a double
      mutant was constructed that changed the Ca2+- and carbohydrate-binding motif from
      the galactose-type of wild-type AFP containing the sequence Gln-Pro-Asp to a
      mannose-type that has the sequence Glu-Pro-Asn and is also known to bind Ca2+.
      The mutant AFP exhibited proper Ca2+ binding, folding, and stability as
      demonstrated by ruthenium red staining, proteolysis protection assays, and CD
      spectroscopy. However, it showed no antifreeze activity (thermal hysteresis) and
      did not alter ice crystal morphology to form bipyramidal crystals as does the
      active wild-type AFP. These results demonstrate that the ice-binding site of the
      herring type II AFP corresponds to the carbohydrate-binding site of the C-type
      lectin CRDs and further suggest that this ice-binding function evolved from the
      carbohydrate-binding site of a preexisting C-type lectin.

PMID- 9521730
TI  - Role of the carboxyl-terminal lectin domain in self-association of galectin-3.
AB  - Galectin-3 is a member of a large family of beta-galactoside-binding animal
      lectins and is composed of a carboxyl-terminal lectin domain connected to an
      amino-terminal nonlectin part. Previous experimental results suggest that, when
      bound to multivalent glycoconjugates, galectin-3 self-associates through
      intermolecular interactions involving the amino-terminal domain. In this study,
      we obtained evidence suggesting that the protein self-associates in the absence
      of its saccharide ligands, in a manner that is dependent on the carboxyl-terminal
      domain. This mode of self-association is inhibitable by the lectin's saccharide
      ligands. Specifically, recombinant human galectin-3 was found to bind to galectin
      3C (the carboxyl-terminal domain fragment) conjugated to Sepharose 4B and the
      binding was inhibitable by lactose. In addition, biotinylated galectin-3 bound to
      galectin-3 immobilized on plastic surfaces and the binding could also be
      inhibited by various saccharide ligands of the lectin. A mutant with a tryptophan
      to leucine replacement in the carboxyl-terminal domain, which exhibited
      diminished carbohydrate-binding activity, did not bind to galectin-3C-Sepharose
      4B. Furthermore, galectin-3C formed covalent homodimers when it was treated with
      a chemical cross-linker and the dimer formation was completely inhibited by
      lactose. Therefore, galectin-3 can self-associate through intermolecular
      interactions involving both the amino- and the carboxyl-terminal domains and the
      relative contribution of each depends on whether the lectin is bound to its
      saccharide ligands.

PMID- 9521731
TI  - Leishmania major pteridine reductase 1 belongs to the short chain dehydrogenase
      family: stereochemical and kinetic evidence.
AB  - Pteridine reductase 1 (PTR1) is a novel broad spectrum enzyme of pterin and
      folate metabolism in the protozoan parasite Leishmania. Overexpression of PTR1
      confers methotrexate resistance to these protozoa, arising from the enzyme's
      ability to reduce dihydrofolate and its relative insensitivity to methotrexate.
      The kinetic mechanism and stereochemical course for the catalyzed reaction
      confirm PTR1's membership within the short chain dehydrogenase/reductase (SDR)
      family. With folate as a substrate, PTR1 catalyzes two rounds of reduction,
      yielding 5,6,7, 8-tetrahydrofolate and oxidizing 2 equiv of NADPH. Dihydrofolate
      accumulates transiently during folate reduction and is both a substrate and an
      inhibitor of PTR1. PTR1 transfers the pro-S hydride of NADPH to carbon 6 on the
      si face of dihydrofolate, producing the same stereoisomer of THF as does
      dihydrofolate reductase. Product inhibition and isotope partitioning studies
      support an ordered ternary complex mechanism, with NADPH binding first and NADP+
      dissociating after the reduced pteridine. Identical kinetic mechanisms and
      NAD(P)H hydride chirality preferences are seen with other SDRs. An observed
      tritium effect upon V/K for reduction of dihydrofolate arising from isotopic
      substitution of the transferred hydride was suppressed at a high concentration of
      dihydrofolate, consistent with a steady-state ordered kinetic mechanism.
      Interestingly, half of the binary enzyme-NADPH complex appears to be incapable of
      rapid turnover. Fluorescence quenching results also indicate the existence of a
      nonproductive binary enzyme-dihydrofolate complex. The nonproductive complexes
      observed between PTR1 and its substrates are unique among members of the SDR
      family and may provide leads for developing antileishmanial therapeutics.

PMID- 9521732
TI  - Identification of the 4-glutamyl radical as an intermediate in the carbon
      skeleton rearrangement catalyzed by coenzyme B12-dependent glutamate mutase from
      Clostridium cochlearium.
AB  - A series of 2H- and 13C-labeled glutamates were used as substrates for coenzyme
      B12-dependent glutamate mutase, which equilibrates (S)-glutamate with (2S,3S)-3
      methylaspartate. These compounds contained the isotopes at C-2, C-3, or C-4 of
      the carbon chain: [2-2H], [3,3-2H2], [4,4-2H2], [2,3,3,4,4-2H5], [2-13C], [3
      13C], and [4-13C]glutamate. Each reaction was monitored by electron paramagnetic
      resonance (EPR) spectroscopy and revealed a similar signal characterized by g'xy
      = 2.1, g'z = 1.985, and A' = 5.0 mT. The interpretation of the spectral data was
      aided by simulations which gave close agreement with experiment. This approach
      underpinned the idea of the formation of a radical pair, consisting of
      cob(II)alamin interacting with an organic radical at a distance of 6.6 +/- 0.9 A.
      Comparison of the hyperfine couplings observed with unlabeled glutamate with
      those from the labeled glutamates enabled a principal contributor to the radical
      pair to be identified as the 4-glutamyl radical. These findings support the
      currently accepted mechanism for the glutamate mutase reaction, i.e., the process
      is initiated through hydrogen atom abstraction from C-4 of glutamate by the 5'
      deoxyadenosyl radical, which is derived by homolysis of the Co-C sigma-bond of
      coenzyme B12.

PMID- 9521733
TI  - Catalysis in human hypoxanthine-guanine phosphoribosyltransferase: Asp 137 acts
      as a general acid/base.
AB  - Hypoxanthine-guanine phosphoribosyltransferase (HGPRTase) catalyzes the
      reversible formation of IMP and GMP from their respective bases hypoxanthine (Hx)
      and guanine (Gua) and the phosphoribosyl donor 5-phosphoribosyl-1-pyrophosphate
      (PRPP). The net formation and cleavage of the nucleosidic bond requires
      removal/addition of a proton at the purine moiety, allowing enzymic catalysis to
      reduce the energy barrier associated with the reaction. The pH profile of kcat
      for IMP pyrophosphorolysis revealed an essential acidic group with pKa of 7.9
      whereas those for IMP or GMP formation indicated involvement of essential basic
      groups. Based on the crystal structure of human HGPRTase,
      protonation/deprotonation is likely to occur at N7 of the purine ring, and Lys
      165 or Asp 137 are each candidates for the general base/acid. We have
      constructed, purified, and kinetically characterized two mutant HGPRTases to test
      this hypothesis. D137N displayed an 18-fold decrease in kcat for nucleotide
      formation with Hx as substrate, a 275-fold decrease in kcat with Gua, and a 500
      fold decrease in kcat for IMP pyrophosphorolysis. D137N also showed lower KD
      values for nucleotides and PRPP. The pH profiles of kcat for D137N were severely
      altered. In contrast to D137N, the kcat for K165Q was decreased only 2-fold in
      the forward reaction and was slightly increased in the reverse reaction. The Km
      and KD values showed that K165Q interacts with substrates more weakly than does
      the wild-type enzyme. Pre-steady-state experiments with K165Q indicated that the
      phosphoribosyl transfer step was fast in the forward reaction, as observed with
      the wild type. In contrast, D137N showed slower phosphoribosyl transfer
      chemistry, although guanine (3000-fold reduction) was affected much more than
      hypoxanthine (32-fold reduction). In conclusion, Asp137 acts as a general
      catalytic acid/base for HGPRTase and Lys165 makes ground-state interactions with
      substrates.

PMID- 9521734
TI  - Mutational analysis of posttranslational heterocycle biosynthesis in the gyrase
      inhibitor microcin B17: distance dependence from propeptide and tolerance for
      substitution in a GSCG cyclizable sequence.
AB  - Microcin B17 (MccB17) is a peptidyl antibiotic that is secreted in stationary
      phase by several strains of Escherichia coli. The antibiotic efficacy of this
      polypeptide depends on the posttranslational modification of eight cysteine and
      serine residues to thiazoles and oxazoles, respectively, within the 69 aa McbA
      structural gene product. Mono- and bisheterocycle formation is mediated by MccB17
      synthetase, an enzyme complex composed of three proteins: McbB, -C, and -D. After
      substrate processing, an N-terminal 26 aa propeptide sequence is cleaved to
      afford the mature antibiotic. A method for the overexpression and rapid
      purification of microcin synthetase has been developed using a calmodulin-binding
      peptide tag. The determinants of substrate recognition and synthetase-mediated
      heterocycle formation were investigated by a systematic evaluation of 15 McbA1-46
      analogues representing minimal substrates containing the first
      bisheterocyclization site (Gly39-Ser40-Cys41-Gly42) and variants thereof. Each
      substrate analogue was overexpressed and affinity-purified as fusions to maltose
      binding protein, incubated with purified synthetase, and evaluated for processing
      by Western blots, UV spectroscopy, and mass spectrometry. Insights gained into
      the process of enzymatic heterocycle formation from cysteine and serine residues
      are discussed, including the distance dependence of the first cyclized residue
      from the propeptide and the local sequence context at the cyclizable sites. A
      model for McbA substrate recognition and processing by MccB17 synthetase is
      proposed.

PMID- 9521735
TI  - Evaluation of atypical cytochrome P450 kinetics with two-substrate models:
      evidence that multiple substrates can simultaneously bind to cytochrome P450
      active sites.
AB  - Some cytochrome P450 catalyzed reactions show atypical kinetics, and these
      kinetic processes can be grouped into five categories: activation,
      autoactivation, partial inhibition, substrate inhibition, and biphasic saturation
      curves. A two-site model in which the enzyme can bind two substrate molecules
      simultaneously is presented which can be used to describe all of these observed
      kinetic properties. Sigmoidal kinetic characteristics were observed for
      carbamazepine metabolism by CYP3A4 and naphthalene metabolism by CYPs 2B6, 2C8,
      2C9, and 3A5 as well as dapsone metabolism by CYP2C9. Naphthalene metabolism by
      CYP3A4 and naproxen metabolism by CYP2C9 demonstrated nonhyperbolic enzyme
      kinetics suggestive of a low Km, low Vmax component for the first substrate
      molecule and a high Km, high Vmax component for the second substrate molecule. 7,
      8-Benzoflavone activation of phenanthrene metabolism by CYP3A4 and dapsone
      activation of flurbiprofen and naproxen metabolism by CYP2C9 were also observed.
      Furthermore, partial inhibition of 7, 8-benzoflavone metabolism by phenanthrene
      was observed. These results demonstrate that various P450 isoforms may exhibit
      atypical enzyme kinetics depending on the substrate(s) employed and that these
      results may be explained by a model which includes simultaneous binding of two
      substrate molecules in the active site.

PMID- 9521737
TI  - Reaction of Escherichia coli cytochrome bo3 with substoichiometric ubiquinol-2: a
      freeze-quench electron paramagnetic resonance investigation.
AB  - The reaction of the quinol oxidase cytochrome bo3 from Escherichia coli with
      ubiquinol-2 (UQ2H2) was carried out using substoichiometric (0.5 equiv) amounts
      of substrate. Reactions were monitored through the use of freeze-quench EPR
      spectroscopy. Under 1 atm of argon, semiquinone was formed at the QB site of the
      enzyme with a formation rate constant of 140 s-1; the QB semiquinone EPR signal
      decayed with a rate constant of about 5 s-1. Heme b and CuB were reduced within
      the 10-ms dead time of the freeze-quench experiment and remained at a constant
      level of reduction over the 1-s time course of the experiment. Quantitation of
      the reduction levels of QB and heme b during this reaction yielded a reduction
      potential of 30-60 mV for heme b. Under a dioxygen atmosphere, the rates of
      semiquinone formation and its subsequent decay were not altered significantly.
      However, accurate quantitation of the EPR signals for heme b and heme o3 could
      not be made, due to interference from dioxygen. In the reaction between the QB
      depleted enzyme and UQ2H2 under substoichiometric conditions, there was no
      observable change in the EPR spectra of the enzyme over the time course of the
      reaction, suggesting an electron transfer from heme b to the binuclear site in
      the absence of QB which occurs within the dead time of the freeze-quench
      apparatus. Analysis of the thermodynamics and kinetics of electron transfers in
      this enzyme suggests that a Q-cycle mechanism for proton translocation is more
      likely than a cytochrome c oxidase-type ion-pump mechanism.

PMID- 9521736
TI  - Localization of histidine residues responsible for heme axial ligation in
      cytochrome b556 of complex II (succinate:ubiquinone oxidoreductase) in
      Escherichia coli.
AB  - Complex II (succinate:ubiquinone oxidoreductase) from Escherichia coli contains
      four different subunits. Two of the subunits (SDHC and SDHD) are hydrophobic and
      anchor the two more hydrophilic (flavin and iron-sulfur) subunits (SDHA and SDHB)
      to the cytoplasmic membrane. Previous studies have shown that the complex of
      SDHC/SDHD is required to maintain the heme B component of the enzyme and that the
      heme B is ligated to the protein by two histidine ligands. In the current work,
      the histidines within SDHC and SDHD have been systematically mutated. SDHC-His91
      and SDHD-His14 were eliminated as potential ligands by these studies. SDHC-His84
      and SDHD-His71 have been identified as the most likely heme axial ligands in the
      E. coli enzyme, suggesting that the heme bridges these two subunits in the
      membrane. Furthermore, the results show that the four-subunit Complex II
      assembles and retains function despite the absence of the heme B prosthetic group
      in the membrane. The results do not rule out completely SDHC-His30 as a candidate
      for heme ligation, but do show that mutation at this position prevents assembly
      of Complex II in the membrane.

PMID- 9521738
TI  - Role of thylakoid lipids in the structural flexibility of lamellar aggregates of
      the isolated light-harvesting chlorophyll a/b complex of photosystem II.
AB  - We studied the role of added thylakoid lipids in the light-induced reversible
      structural changes in isolated macroaggregates of the main light-harvesting
      chlorophyll a/b complex of photosystem II (LHCII). Loosely stacked lamellar
      macroaggregates were earlier shown to undergo light-induced reversible structural
      changes and changes in the photophysical pathways, which resembled those in
      thylakoid membranes exposed to excess light [Barzda, V., et al. (1996)
      Biochemistry 35, 8981-8985]. This structural flexibility of LHCII depends
      critically on the lipid content of the preparations [Simidjiev, I., et al. (1997)
      Anal. Biochem. 250, 169-175]. It is now reported that lamellar aggregates of
      LHCII are capable of incorporating substantial amounts of different thylakoid
      lipids. The long-range order of the chromophores is retained, while the
      ultrastructure of the lipid-protein macroaggregates can be modified
      significantly. Addition of thylakoid lipids to the preparations significantly
      enhances the ability of the LHCII macroaggregates to undergo light-induced
      structural changes. The lipid environment of the LHCII complexes therefore plays
      a significant role in determining the structural flexibility of the
      macroaggregates. As concerns the mechanism of these changes, it is proposed that
      the absorption of light and the dissipation of its energy in the macrodomains
      induces thermal fluctuations which bring about changes in the shape or in the
      stacking interactions of the membranes, this in turn affecting the long-range
      order of the embedded chromophores. In thylakoids, a similar mechanism is likely
      to explain the light-induced structural changes which are largely independent of
      the photochemical activity of the membranes.

PMID- 9521739
TI  - Structural requirements for human inducible nitric oxide synthase substrates and
      substrate analogue inhibitors.
AB  - Inducible nitric oxide synthase (iNOS; EC 1.14.13.39) catalyzes the NADPH
      dependent oxidation of one of the free guanidino nitrogens of L-Arg to form
      nitric oxide and L-citrulline. Analogues of L-Arg and the inhibitor, L-N6-(1
      iminoethyl)lysine, were used to define structural elements required for the
      binding and catalysis of compounds. L-Arg analogues with sequentially shorter
      methylene spacing between the guanidino group and the amino acid portion of the
      molecule were not iNOS substrates but were reversible inhibitors. L-Arg analogues
      such as agmatine with a hydroxyl substitution at the 2-amino position were
      substrates. Desaminoarginine was not a substrate but a reversible inhibitor.
      Desaminoarginine, agmatine, and argininic acid bound to the enzyme to give type I
      difference spectra similar to that of L-Arg. The amidino compounds L-N6-(1
      iminoethyl)lysine, L-N5-(1-iminoethyl)ornithine, and N5-(1
      iminoethyl)cadaverdine, but not N6-(1-iminoethyl)-6-aminocaproic acid, were NADPH
      dependent, irreversible inactivators of iNOS. For both the L-Arg and L-N6-(1
      iminoethyl)lysine analogues, the 2-amino group appeared to play an important role
      in catalytic events leading to either substrate turnover or mechanism-based
      inactivation. Inactivation of iNOS by L-N6-(1-iminoethyl)lysine was NADPH- and
      dioxygen-dependent, but low incorporation of radiolabel with DL--4, 5-3H]-N6-(1
      iminoethyl)lysine indicates that the mechanism of enzyme inactivation is not
      covalent modification of the protein.

PMID- 9521740
TI  - Conversion of a cosubstrate to an inhibitor: phosphorylation mutants of nicotinic
      acid phosphoribosyltransferase.
AB  - Nicotinic acid phosphoribosyltransferase (NAPRTase; EC 2.4.2.11) forms nicotinic
      acid mononucleotide (NAMN) and PPi from 5-phosphoribosyl 1-pyrophosphate (PRPP)
      and nicotinic acid (NA). The Vmax NAMN synthesis activity of the Salmonella
      typhimurium enzyme is stimulated about 10-fold by ATP, which, when present, is
      hydrolyzed to ADP and Pi in 1:1 stoichiometry with NAMN formed. The overall
      NAPRTase reaction involves phosphorylation of a low-affinity form of the enzyme
      by ATP, followed by generation of a high-affinity form of the enzyme, which then
      binds substrates and produces NAMN. Hydrolysis of E-P then regenerates the low
      affinity form of the enzyme with subsequent release of products. Our earlier
      studies [Gross, J., Rajavel, M., Segura, E., and Grubmeyer, C. (1996)
      Biochemistry 35, 3917-3924] have shown that His-219 becomes phosphorylated in the
      N1 (pi) position by ATP. Here, we have mutated His-219 to glutamate and
      asparagine and determined the properties of the purified mutant enzymes. The
      mutant NAPRTases fail to carry out ATPase, autophosphorylation, or ADP/ATP
      exchanges seen with wild-type (WT) enzyme. The mutants do catalyze the slow
      formation of NAMN in the absence of ATP with rates and KM values similar to those
      of WT. In striking contrast to WT, NAMN formation by the mutant enzymes is
      competitively inhibited by ATP. Thus, the NAMN synthesis reaction may occur at a
      site overlapping that for ATP. Previous studies suggest that the yeast NAPRTase
      does not catalyze NAMN synthesis in the absence of ATP. We have cloned,
      overexpressed, and purified the yeast enzyme and report its kinetic properties,
      which are similar to those of the bacterial enzyme.

PMID- 9521741
TI  - Kinetic mechanism of nicotinic acid phosphoribosyltransferase: implications for
      energy coupling.
AB  - Nicotinic acid phosphoribosyltransferase (NAPRTase; EC 2.4.2.11) is a facultative
      ATPase that uses the energy of ATP hydrolysis to drive the synthesis of
      nicotinate mononucleotide and pyrophosphate from nicotinic acid (NA) and
      phosphoribosyl pyrophosphate (PRPP). To learn how NAPRTase uses this hydrolytic
      energy, we have further delineated the kinetic mechanism using steady-state and
      pre-steady-state kinetics, equilibrium binding, and isotope trapping. NAPRTase
      undergoes covalent phosphorylation by bound ATP at a rate of 30 s-1. The
      phosphoenzyme (E-P) binds PRPP with a KD of 0.6 microM, a value 2000-fold lower
      than that measured for the nonphosphorylated enzyme. The minimal rate constant
      for PRPP binding to E-P is 0.72 x 10(5) M-1 s-1. Isotope trapping shows that
      greater than 90% of bound PRPP partitions toward product upon addition of NA.
      Binding of NA to E-P.PRPP is rapid, kon >/= 7.0 x 10(6) M-1 s-1, and is followed
      by rapid formation of NAMN and PPi, k >/= 500 s-1. After product formation, E-P
      undergoes hydrolytic cleavage, k = 6.3 s-1, and products NAMN, PPi, and Pi are
      released. Quenching from the steady state under Vmax conditions indicates that
      slightly less than half the enzyme is in phosphorylated forms. To account for
      this finding, we propose that one step in the release of products is as slow as
      5.2 s-1 and, together with the E-P cleavage step, codetermines the overall kcat
      of 2.3 s-1 at 22 degrees C. Energy coupling by NAPRTase involves two strategies
      frequently proposed for ATPases of macromolecular recognition and processing.
      First, E-P has a 10(3)-fold higher affinity for substrates than does
      nonphosphorylated enzyme, allowing the E-P to bind substrate from low
      concentration and nonphosphorylated enzyme to expel products against a high
      concentration. Second, the kinetic pathway follows "rules" [Jencks, W. P. (1989)
      J. Biol. Chem. 264, 18855-18858] that minimize unproductive alternative reaction
      pathways. However, an analysis of reaction schemes based on these strategies
      suggests that such nonvectorial reactions are intrinsically inefficient in ATP
      use.

PMID- 9521742
TI  - Hydropathic analysis and mutagenesis of the catalytic domain of the cGMP-binding
      cGMP-specific phosphodiesterase (PDE5). cGMP versus cAMP substrate selectivity.
AB  - The mechanism of discrimination between cGMP and cAMP in the catalytic site of
      the cGMP-binding cGMP-specific phosphodiesterase (BTPDE5A1 or PDE5) has been
      investigated. A hydropathy analysis of the catalytic domains of different
      families of PDEs suggests that substrate selectivity of PDEs could result from
      the pattern of hydrophobic/hydrophilic residues in a short segment surrounding a
      conserved Glu that has been shown to be critical for cGMP binding in the
      catalytic domain of PDE5. This implies that the substrate selectivity of PDE5
      could be altered by replacing the residues within this segment that are conserved
      in cGMP-specific PDEs with the conserved residues in the corresponding positions
      of cAMP-specific PDEs. The A769T/L771R, W762L/Q765Y, and W762L/Q765Y/A769T/L771R
      mutant PDE5s were expressed in High Five cells, and their substrate selectivities
      were compared with that of wild-type PDE5. The results indicate that the
      substrate-binding site of PDE5 contains positive elements for accommodating cGMP,
      as well as negative elements that discriminate against binding of cAMP, and that
      the cGMP/cAMP selectivity of PDE5 can be shifted 106-fold by substituting four
      residues of PDE5 with the residues in the corresponding positions of PDE4.

PMID- 9521743
TI  - Nonequilibrium analysis alters the mechanistic interpretation of inhibition of
      acetylcholinesterase by peripheral site ligands.
AB  - The active site gorge of acetylcholinesterase (AChE) contains two sites of ligand
      binding, an acylation site near the base of the gorge with a catalytic triad
      characteristic of serine hydrolases, and a peripheral site at the mouth of the
      gorge some 10-20 A from the acylation site. Many ligands that bind exclusively to
      the peripheral site inhibit substrate hydrolysis at the acylation site, but the
      mechanistic interpretation of this inhibition has been unclear. Previous
      interpretations have been based on analyses of inhibition patterns obtained from
      steady-state kinetic models that assume equilibrium ligand binding. These
      analyses indicate that inhibitors bound to the peripheral site decrease acylation
      and deacylation rate constants and/or decrease substrate affinity at the
      acylation site by factors of up to 100. Conformational interactions have been
      proposed to account for such large inhibitory effects transmitted over the
      distance between the two sites, but site-specific mutagenesis has failed to
      reveal residues that mediate the proposed conformational linkage. Since
      examination of individual rate constants in the AChE catalytic pathway reveals
      that assumptions of equilibrium ligand binding cannot be justified, we introduce
      here an alternative nonequilibrium analysis of the steady-state inhibition
      patterns. This analysis incorporates a steric blockade hypothesis which assumes
      that the only effect of a bound peripheral site ligand is to decrease the
      association and dissociation rate constants for an acylation site ligand without
      altering the equilibrium constant for ligand binding to the acylation site.
      Simulations based on this nonequilibrium steric blockade model were in good
      agreement with experimental data for inhibition by the peripheral site ligands
      propidium and gallamine at low concentrations of either acetylthiocholine or
      phenyl acetate if binding of these ligands slows substrate association and
      dissociation rate constants by factors of 5-70. Direct measurements with the
      acylation site ligands huperzine A and m-(N,N, N
      trimethylammonio)trifluoroacetophenone showed that bound propidium decreased the
      association rate constants 49- and 380-fold and the dissociation rate constants
      10- and 60-fold, respectively, relative to the rate constants for these acylation
      site ligands with free AChE, in reasonable agreement with the nonequilibrium
      steric blockade model. We conclude that this model can account for the inhibition
      of AChE by small peripheral site ligands such as propidium without invoking any
      conformational interaction between the peripheral and acylation sites.

PMID- 9521744
TI  - Thermodynamics of the DNA binding reaction of transcription factor MASH-1.
AB  - MASH-1, a member of the basic helix-loop-helix (BHLH) family of transcription
      factors, promotes the differentiation of committed neuronal precursor cells. We
      have determined the thermodynamic parameters of the DNA binding reaction of the
      BHLH domain of MASH-1 (MASH-BHLH) by isothermal titration calorimetry and found
      that the specificity of the binding reaction was rather low. At 27 degrees C, the
      association constant for binding was 5.13 (+/-0.51) x 10(8) M-1 for an E-box
      containing oligonucleotide, while for a heterologous DNA sequence it was 5.14 (+/
      1.93) x 10(7) M-1. The reaction enthalpy and the reaction entropy were strongly
      dependent on the temperature, but the reaction free energy was almost independent
      of temperature. The association reaction was enthalpically driven throughout the
      physiological temperature range and characterized by a large negative heat
      capacity change. No change in the protonation state of the protein and/or the DNA
      was observed at pH 6. Within experimental error, the reaction was independent of
      pH between pH 6 and 8. Dissection of the entropy change of the binding reaction
      indicated that binding was coupled to local protein folding of approximately 25
      amino acids per protein subunit. The circular dichroism spectra of free and DNA
      bound MASH-BHLH revealed the formation of additional alpha-helical structure
      comprising approximately 25 amino acids upon complex formation. Therefore, while
      the basic region was in an alpha-helical conformation in the DNA complex, in free
      MASH-BHLH it was substantially unfolded even at concentrations where the protein
      is mainly dimeric. The association between MASH-1 and DNA is therefore an example
      of "induced fit".

PMID- 9521745
TI  - A Tetrahymena thermophila G4-DNA binding protein with dihydrolipoamide
      dehydrogenase activity.
AB  - G4-DNA is a four-stranded structure that is formed by guanine-rich sequences. We
      report here the purification and characterization of a novel G4-DNA binding
      protein from Tetrahymena thermophila, designated TGP2. TGP2 was found to
      preferentially bind to G4-DNA oligonucleotides with adjacent single-stranded
      domains containing phosphorylated 5' ends and the sequence element, 5'-ACTG-3'.
      The amino acid sequence of TGP2 has high similarity to dihydrolipoamide
      dehydrogenase (DLDH) from a variety of species, and TGP2 was shown to have DLDH
      activity. Purified DLDH from porcine heart and bovine intestinal mucosa were
      shown to bind specifically to G4-DNA oligonucleotides. On the basis of these
      results we conclude that TGP2 is DLDH in T. thermophila and suggest that the G4
      DNA binding capability of TGP2/DLDH may be biologically relevant.

PMID- 9521746
TI  - RNA-protein interactions in the Tat-trans-activation response element complex
      determined by site-specific photo-cross-linking.
AB  - Transcriptional regulation in human immunodeficiency virus type 1 (HIV-1)
      requires specific interactions of Tat protein with the trans-activation
      responsive region (TAR) RNA, a 59-base stem-loop structure located at the 5'-end
      of all HIV transcripts. We have used a site-specific cross-linking method based
      on 6-thioguanosine (6-thioG) photochemistry to determine the conformation of TAR
      RNA and its interaction with Tat protein under physiological conditions. Two
      different TAR RNA constructs with a single photoactive nucleoside (6-thioG) at
      position 21 or 26 were synthesized. Upon UV irradiation, 6-thioG at both
      positions formed interstrand covalent cross-links in TAR RNA. Determination of
      cross-link sites by RNA sequencing revealed that 6-thioG at position 21 contacts
      U42, while a 6-thioG at position 26 cross-links to C39. The addition of arginine
      did not alter the site of RNA-RNA cross-links; however, the yields of 6-thioG26
      C39 cross-link were decreased. In the presence of a Tat fragment, Tat(38-72), UV
      irradiation of RNA modified with 6-thioG at position 21 resulted in RNA-protein
      cross-links but no RNA-RNA cross-links were observed. 6-thioG at position 26
      formed both RNA-RNA and RNA-protein cross-links in the presence of Tat(38-72).
      Our results provide direct evidence that, during RNA-protein recognition, Tat is
      in close proximity to O6 of G21 and G26 in the major groove of TAR RNA.

PMID- 9521747
TI  - Interactions between domains of apo calmodulin alter calcium binding and
      stability.
AB  - Calmodulin (CaM) is an essential protein that exerts exquisite spatial and
      temporal control over diverse eukaryotic processes. Although the two half
      molecule domains of CaM each have two EF-hands and bind two calcium ions
      cooperatively, they have distinct roles in activation of some targets.
      Interdomain interactions may mediate coordination of their actions. Proteolytic
      footprinting titrations of CaM [Pedigo and Shea (1995) Biochemistry 34, 1179
      1196; Shea, Verhoeven, and Pedigo (1996) Biochemistry 35, 2943-2957] showed that
      calcium binding to the high-affinity sites (III and IV in the C-domain) alters
      the conformation of helix B in the N-domain despite sites I and II being vacant.
      This may arise from calcium-induced disruption of interactions between the apo
      domains. In this study, comparing the cloned domains (residues 1-75, 76-148) to
      whole CaM, the proteolytic susceptibility of helix B in the apo isolated N-domain
      was higher than in apo CaM. The isolated N-domain was monotonically protected by
      calcium binding and had a higher calcium affinity than when part of whole CaM.
      The change in affinity was small (1-1.5 kcal/mol) but acted to separate the
      domain saturation curves of whole CaM. Unfolding enthalpies and melting
      temperatures of the apo isolated domains did not correspond to the two
      transitions resolved for apo CaM. In summary, the interactions between domains of
      apo CaM protected the N-domain from proteolysis and raised its Tm by 10 degrees
      C, demonstrating that CaM is not the sum of its parts.

PMID- 9521749
TI  - Cyclopiazonic acid effect on Ca2+-dependent conformational states of the
      sarcoplasmic reticulum ATPase. Implication for the enzyme turnover.
AB  - The affinity of sarcoplasmic reticulum Ca2+-ATPase for cyclopiazonic acid is
      dependent on the conformational state of the enzyme. It is high in the absence of
      Ca2+ but low in its presence. When Ca2+ was added to the enzyme in the presence
      of equimolar toxin, the apparent rate constant for Ca2+ binding was 0.6 min-1
      when measured at 37 degrees C. The apparent equilibrium constant for Ca2+
      dissociation increased from 0.2 to 0.6 microM at neutral pH, and from 5.9 to 37
      microM at pH 6.0. The apparent equilibrium constant for Ca2+ dissociation
      increased progressively as the amount of toxin increased above an equimolar
      level. Cyclopiazonic acid decreased phosphorylation by ATP and Ca2+ when the
      enzyme in the absence of Ca2+ was incubated in the presence of toxin, although no
      effect was observed after a preliminary incubation with Ca2+ at 37 degrees C.
      Cyclopiazonic acid incubated with the enzyme in the presence of Ca2+ could be
      eliminated with a Sephadex column. However, the toxin could not be removed when
      it was incubated with the enzyme in the absence of Ca2+. In the latter case,
      cyclopiazonic acid was eliminated when the enzyme in the presence of toxin was
      incubated with Ca2+ at 37 degrees C. Under turnover conditions and in the
      presence of 10 microM ATP, the toxin-enzyme interaction can be characterized by
      an apparent Kd of 7 nM. With an ATP concentration of 1 mM, the enzyme was
      inhibited completely at a toxin/enzyme molar ratio of approximately 10.
      Furthermore, enzyme activity was observed to recover at a toxin/enzyme molar
      ratio of 1 when the Ca2+ concentration was raised, which is consistent with the
      competitive character of cyclopiazonic acid and Ca2+. It is concluded that ATP
      and Ca2+ can protect against cyclopiazonic acid inhibition.

PMID- 9521748
TI  - Protonation behavior of histidine 24 and histidine 119 in forming the pH 4
      folding intermediate of apomyoglobin.
AB  - Heteronuclear NMR methods are used to study the protonation of histidine and
      aspartate residues in the acid-induced unfolding of recombinant sperm whale
      apomyoglobin. The results are combined with fluorescence and circular dichroism
      measurements of acid-induced unfolding of wild-type and double mutant
      (H24V/H119F) proteins. They are consistent with a simple model in which the
      failure to protonate a single buried histidine, H24, is largely responsible for
      the partial unfolding of native (N) wild-type apomyoglobin to the pH 4 folding
      intermediate (I). H24 is known to form an unusual interaction in which its side
      chain is buried and hydrogen-bonded to the side chain of H119. Two-dimensional 1H
      15N heteronuclear NMR spectra indicate that H24 is present in the rare delta
      tautomeric form and remains neutral until N unfolds to I, while H119 becomes
      protonated before the N --> I reaction occurs. In the H24V/H119F double mutant,
      all histidines are protonated in N and the N --> I reaction occurs at lower pH.
      Therefore, the protonation of aspartate and/or glutamate residues must provide an
      additional driving force for the N to I reaction. Two-dimensional 1H-13C NMR
      experiments are used to measure the protonation of aspartates in selectively 13C
      labeled apomyoglobin; the results indicate that none of the aspartate residues
      has a strongly depressed pKa in N, as would be expected if it forms a stabilizing
      salt bridge.

PMID- 9521750
TI  - Engineering of the nonspecific phospholipase C from Bacillus cereus: replacement
      of glutamic acid-4 by alanine results in loss of interfacial catalysis and
      enhanced phosphomonoesterase activity.
AB  - The nonspecific phospholipase C from Bacillus cereus is a zinc metalloenzyme that
      catalyzes the hydrolysis of phospholipids to yield diacylglycerol and a phosphate
      monoester. Glu-4 has been proposed as a potential candidate for the general base
      in the hydrolysis reaction and was shown to interact with the substrate
      headgroup. Site-specific mutagenesis studies suggest that Glu-4 is important for
      substrate binding but not for catalysis. This residue is also critical for the
      enzyme's preference for a phosphodiester substrate. PA, both monomeric and
      micellar, is shown to be a poor substrate and inhibitor of wild-type PLC. When
      Glu-4 was mutated to an alanine, a significant increase in PA hydrolysis and a
      decrease in PC hydrolysis were observed. Unlike the wild type, kinetic studies
      suggest that the Glu-4-->Ala mutant does not exhibit interfacial activation and
      processive catalysis. Glu-4 is part of a highly flexible loop flanking the
      entrance to the active site, suggesting that this loop might constitute an
      interfacial binding recognition site. This is the first evidence for the presence
      of an interfacial binding site distinct from the active site in the nonspecific
      PLC.

PMID- 9521751
TI  - Characterization of AT4 receptor from bovine aortic endothelium with
      photosensitive analogues of angiotensin IV.
AB  - Newly developed photosensitive analogues of AngIV were used to characterize the
      AT4 receptor of bovine aortic endothelial cells. The photoactivatable AngIV
      analogues [N3-Phe6]AngIV and [Bpa6]AngIV displayed high affinities for AT4
      receptor, with IC50's of 3.7 +/- 0.3 and 19.1 +/- 3.5 nM, respectively. The
      radioiodinated ligands showed a good efficiency of photoaffinity labeling
      demonstrated by high proportions (60-75%) of acid-resistant binding. Covalently
      labeled receptor was solubilized under reducing or nonreducing conditions and
      subjected to SDS-PAGE. Under nonreducing conditions, autoradiographies revealed a
      major band of Mr 186 +/- 2 kDa and a minor band of Mr 241 +/- 6 kDa. The labeling
      of these bands was completely abolished in the presence of 10 microM AngIV. Under
      reducing conditions, only the low Mr 186 kDa band was revealed. After
      endoglycosidase digestion with an enzyme that cleaves N-linked saccharides, the
      Mr of the denatured AT4 receptor was decreased by 31% to a value of 129 +/- 10
      kDa. Kinetic studies revealed a stepwise process of AT4 receptor deglycosylation
      by endoglycosidase F, suggesting at least two different sites of N-linked
      saccharides. Mild trypsin treatment of photolabeled endothelial cell membranes
      released a large fragment of Mr 177 +/- 3 kDa which accounts for about 95% of the
      whole receptor molecular mass. These results demonstrate that [N3-Phe6]AngIV and
      [Bpa6]AngIV are very efficient tools for selective photoaffinity labeling of AT4
      receptor. We have shown that AT4 receptor is a 186 kDa integral membrane
      glycoprotein with a very large extracellular domain. These properties are
      consistent with those of a growth factor or cytokine receptor.

PMID- 9521752
TI  - Three-dimensional solution structure of lactoferricin B, an antimicrobial peptide
      derived from bovine lactoferrin.
AB  - The solution structure of bovine lactoferricin (LfcinB) has been determined using
      2D 1H NMR spectroscopy. LfcinB is a 25-residue antimicrobial peptide released by
      pepsin cleavage of lactoferrin, an 80 kDa iron-binding glycoprotein with many
      immunologically important functions. The NMR structure of LfcinB reveals a
      somewhat distorted antiparallel beta-sheet. This contrasts with the X-ray
      structure of bovine lactoferrin, in which residues 1-13 (of LfcinB) form an alpha
      helix. Hence, this region of lactoferricin B appears able to adopt a helical or
      sheetlike conformation, similar to what has been proposed for the amyloidogenic
      prion proteins and Alzheimer's beta-peptides. LfcinB has an extended hydrophobic
      surface comprised of residues Phe1, Cys3, Trp6, Trp8, Pro16, Ile18, and Cys20.
      The side chains of these residues are well-defined in the NMR structure. Many
      hydrophilic and positively charged residues surround the hydrophobic surface,
      giving LfcinB an amphipathic character. LfcinB bears numerous similarities to a
      vast number of cationic peptides which exert their antimicrobial activities
      through membrane disruption. The structures of many of these peptides have been
      well characterized, and models of their membrane-permeabilizing mechanisms have
      been proposed. The NMR solution structure of LfcinB may be more relevant to
      membrane interaction than that suggested by the X-ray structure of intact
      lactoferrin. Based on the solution structure, it is now possible to propose
      potential mechanisms for the antimicrobial action of LfcinB.

PMID- 9521754
TI  - Thermodynamic studies on the equilibrium properties of a series of recombinant
      betaW37 hemoglobin mutants.
AB  - In human hemoglobin (Hb) the beta37 tryptophan residue (betaW37), located at the
      hinge region of the alpha1beta2 interface, forms many contacts with alpha subunit
      residues of the opposite dimer, in both the T and R quaternary structures. We
      have carried out equilibrium O2 binding studies on a series of recombinant Hbs
      that have mutations at this residue site: betaW37Y, betaW37A, betaW37G, and
      betaW37E. Binding isotherms measured at high concentrations of these mutants were
      found to be shifted toward increased affinity and decreased cooperativity from
      that of the normal HbA0 tetramer. Analysis of these binding isotherms indicated
      that amino acid substitutions at the beta37 position could both destabilize the
      tetrameric form of the mutants relative to their constituent dimers and also
      alter cooperativity of the intact tetrameric species. These alterations from wild
      type function are dependent on the particular side chain substituted, with the
      magnitude of change increasing as Trp is substituted by Tyr, Ala, Gly, and Glu.
      The dimer to tetramer assembly free energy of deoxy-betaW37E, the most perturbed
      mutant in the series, was measured using analytical gel chromatography to be 9
      kcal/tetramer less favorable than that of deoxy HbA0. Stabilizing the betaW37E
      tetramer by addition of IHP, or by cross-linking at the alphaK99 positions, does
      not restore normal O2 binding behavior. Thermodynamic parameters of all the
      mutants were found to correlate with their CO binding rates and with their high
      resolution X-ray crystal structures (see accompanying papers: Kwiatkowski et al.
      (1998) Biochemistry 37, 4325-4335; Peterson & Friedman (1998) Biochemistry 37,
      4346-4357; Kavanaugh et al. (1998) Biochemistry 37, 4358-4373].

PMID- 9521753
TI  - Preparation and kinetic characterization of a series of betaW37 variants of human
      hemoglobin A: evidence for high-affinity T quaternary structures.
AB  - Four variants of human beta globin in which the Trp at position 37 has been
      replaced with a Tyr, Ala, Gly, or Glu have been expressed in Escherichia coli.
      These globins have been combined with normal human alpha chains and heme to form
      tetrameric hemoglobin molecules. A technique for the preparation of alpha chain
      dimers, which are cross-linked between their alpha99 lysine residues, has been
      developed, and these alpha dimers were combined with two of the beta globins,
      betaW37G and betaW37E, to form the corresponding cross-linked variants. The
      kinetics of CO binding to the deoxygenated derivatives following rapid mixing and
      of CO rebinding following flash photolysis have been examined as functions of pH
      in the presence and absence of the organic phosphate inositol hexaphosphate, IHP.
      The kinetic measurements indicate that replacement of the tryptophan with other
      residues destabilizes the hemoglobin tetramer, resulting in considerable
      dissociation of even the deoxygenated hemoglobins into alphabeta dimers at
      micromolar protein concentrations. Substitutions at beta37 also alter the
      properties of the deoxygenated hemoglobin tetramer. The alteration of the
      functional properties of the T states of these variants as well as the tendency
      of the deoxygenated derivatives to dissociate into alphabeta dimers increases in
      the order HbA < betaW37Y < betaW37A < betaW37G < betaW37E. Stabilizing the
      betaW37G or betaW37E tetramers by addition of IHP or by cross-linking does not
      restore the normal functional properties of the T state. Measurements of the
      geminate rebinding of CO establish a kinetic difference between the normal R
      state tetramer and the alphabeta dimer consistent with quaternary enhancement,
      the greater affinity of oxygen for the R state tetramer than for the alphabeta
      dimer. Kinetics of geminate rebinding also suggest that quaternary enhancement
      may be altered by substitutions at the beta37 position.

PMID- 9521755
TI  - A possible allosteric communication pathway identified through a resonance Raman
      study of four beta37 mutants of human hemoglobin A.
AB  - The highly conserved tryptophan at position beta37 occupies a key locus at the
      hinge region within the alpha1beta2 interface of the mammalian hemoglobins. This
      residue is thought to play an important role in mediating the heme-heme
      interaction associated with the cooperative binding of oxygen; however, its
      explicit function is unclear. In this study, the proximal heme environments of
      several beta37 mutants of adult human hemoglobin (HbA) are probed using visible
      (Soret band enhanced) resonance Raman spectroscopy. In the equilibrium deoxy
      derivatives of these mutants, a systematic variation in proximal strain, as
      reflected in the iron-proximal histidine (F8) stretching frequency, nu(Fe-His),
      is seen upon mutation of the beta37 residue. The variation in proximal strain
      correlates with both the ligand binding rates [Kwiatkowski et al. (1998)
      Biochemistry 37, 4325-4335] and conformational changes observed at the FG corner
      through X-ray crystallography [Kavanaugh et al. (1998) Biochemistry 37, 4358
      4373]. The results from the deoxy samples indicate a plasticity of the tertiary
      structure within the T quaternary state. The correlation between the X-ray data
      and the Raman supports the idea that the proximal strain at the heme within the T
      state can be modulated by a combination of forces including those arising from
      the hinge region of the alpha1beta2 interface, from the binding of allosteric
      effectors, and from the degree of iron displacement from the heme plane. Each of
      these contributors appears to operate through a shifting of the F helix either
      away from or toward the FG corner. The Raman spectra obtained from the 10 ns CO
      photoproduct of the beta37 mutant Hb's indicate that these mutants contain an
      altered coupling between the R state alpha1beta2 interface and the proximal heme
      environment. This altered coupling could be due to either dissociation of the
      ligated mutant tetramers into dimers or the formation of an R state tetramer with
      significantly weakened hydrogen bonds and van der Waals contacts between the
      alpha1 and beta2 subunits at the interface. In either case, the results reveal a
      clear-cut structural basis for the quaternary enhancement effect in which the
      normal R state quaternary structure produces a higher affinity ligand binding
      site than that which occurs in the corresponding dimeric form of the protein. The
      normal R state interface is shown to be important for stabilizing a favorable
      ligand binding environment that persists long enough after laser photolysis to
      enhance the geminate rebinding process within the photoproduct. The addition of
      IHP to the solution of mutant COHb proteins results in photoproduct spectra that
      are all identical and are consistent with the ligand-bound derivatives having
      either a T state structure or a very strained and anomalous R state structure.

PMID- 9521756
TI  - High-resolution crystal structures of human hemoglobin with mutations at
      tryptophan 37beta: structural basis for a high-affinity T-state,.
AB  - The high-resolution X-ray structures of the deoxy forms of four recombinant
      hemoglobins in which Trp37(C3)beta is replaced with Tyr (betaW37Y), Ala
      (betaW37A), Glu (betaW37E), or Gly (betaW37G) have been refined and analyzed with
      superposition methods that partition mutation-induced perturbations into
      quaternary structure changes and tertiary structure changes. In addition, a new
      cross-validation statistic that is sensitive to local changes in structure (a
      "local Rfree" parameter) was used as an objective measure of the significance of
      the tertiary structure changes. No significant mutation-induced changes in
      tertiary structure are detected at the mutation site itself for any of the four
      mutants studied. Instead, disruption of the intersubunit contacts associated with
      Trp37(C3)beta results in (1) a change in quaternary structure at the alpha1beta2
      interface, (2) alpha subunit tertiary structure changes that are centered at
      Asp94(G1)alpha-Pro95(G2)alpha, (3) beta subunit tertiary structure changes that
      are located between residues Asp99(G1)beta and Asn102(G4)beta, (4) increased
      mobility of the alpha subunit COOH-terminal dipeptide, and (5) shortening of the
      Fe-Nepsilon2His(F8) bond in the alpha and beta subunits of the betaW37G and
      betaW37E mutants. In each case, the magnitude of the change in a particular
      structural parameter increases in the order betaW37Y < betaW37A < betaW37E
      approximately betaW37G, which corresponds closely to the degree of functional
      disruption documented in the preceding papers.

PMID- 9521757
TI  - An intercalated and thermally stable FAPY adduct of aflatoxin B1 in a DNA duplex:
      structural refinement from 1H NMR.
AB  - The structure of a formamidopyrimidine (FAPY) adduct arising from imidazole ring
      opening of the initially formed trans-8, 9-dihydro-8-(N7-guanyl)-9
      hydroxyaflatoxin B1 adduct under basic conditions and positioned in the 5'
      d(CTATFAPYGATTCA)-3'*5'-d(TGAATCATAG)-3' oligodeoxynucleotide was determined. The
      FAPY adduct may be a major progenitor of aflatoxin B1-induced mutations in DNA.
      The freshly prepared sample showed biphasic melting, with transitions at 28 and
      56 degreesC. NMR initially showed multiple subspectra. Over a period of several
      days at 4 degreesC, the sample converted to a single species with a Tm of 56
      degreesC, 15 degrees C greater than the unmodified duplex. The deoxyribose was in
      the beta configuration about the anomeric carbon, evidenced by NOEs between
      FAPYG5 H3', H2', H2", and H1'. FAPY formation resulted in the loss of the guanine
      H8 proton, and the introduction of the formyl proton, which showed NOEs to FAPYG5
      H1' and A6 N6Ha. A total of 31 NOEs from AFB1 to DNA protons were observed,
      mostly to the 5'-neighboring base, T4 in the modified strand. Sequential NOEs
      were interrupted between T4 and FAPYG5 in the modified strand, between C16 and
      A17 in the complementary strand, and between T4 N3H and FAPYG5 N1H. An NOE
      between FAPYG5 N1H and C16 N4H showed intact hydrogen bonding at FAPYG5*C16.
      Upfield chemical shifts were observed for T4 H6 and A17 H8. Molecular dynamics
      calculations converged with pairwise rmsd differences of <0.9 A. The sixth root
      residual was 8.7 x 10(-2). The AFB1 moiety intercalated from the major groove
      between FAPYG5 and T4*A17, and stacked with T4 and FAPYG5 and partially stacked
      with A17. The base step between T4*A17 and FAPYG5*C16 was increased from 3.4 to 7
      A. The duplex unwound by about 15 degrees. The FAPY formyl group was positioned
      to form a hydrogen bond with A6 N6Ha. Strong stacking involving the AFB1 moiety,
      and this hydrogen bond explains the thermal stabilization of four base pairs by
      this adduct, and may be a significant factor in its processing.

PMID- 9521758
TI  - Crystal structure of fructose-1,6-bisphosphate aldolase from the human malaria
      parasite Plasmodium falciparum.
AB  - The structure of the glycolytic enzyme class I fructose-1, 6-bisphosphate
      aldolase from the human malaria parasite Plasmodium falciparum has been
      determined by X-ray crystallography. Homotetrameric P. falciparum aldolase
      (PfALDO) crystallizes in space group P3221 with one 80 kDa dimer per asymmetric
      unit. The final refined PfALDO model has an R-factor of 0.239 and an R-free of
      0.329 with respect to data from 8 to 3.0 A resolution. PfALDO is potentially a
      target for antimalarial drug design as the intraerythrocytic merozoite lifestage
      of P. falciparum is completely dependent upon glycolysis for its ATP production.
      Thus, inhibitors directed against the glycolytic enzymes in P. falciparum may be
      effective in killing the parasite. The structure of PfALDO is compared with the
      previously determined structure of human aldolase in order to determine possible
      targets for the structure-based design of selective PfALDO ligands. The salient
      structural differences include a hydrophobic pocket on the surface of PfALDO,
      which results from some amino acid changes and a single residue deletion compared
      with human aldolase, and the overall quaternary structure of the PfALDO tetramer,
      which buries less surface area than human aldolase.

PMID- 9521759
TI  - Determining protein-protein interactions by oxidative cross-linking of a glycine
      glycine-histidine fusion protein.
AB  - The Ni(II) complex of the tripeptide NH2-glycine-glycine-histidine-COOH (GGH)
      mediates efficient protein-protein cross-linking in the presence of oxidants such
      as oxone and monoperoxyphthalic acid (MMPP). Here we demonstrate that GGH fused
      to the amino terminus of a protein can still support cross-linking. The
      tripeptide was expressed at the amino terminus of ecotin, a dimeric
      macromolecular serine protease inhibitor found in the periplasm of Escherichia
      coli. In the presence of Ni(OAc)2 and MMPP, GGH-ecotin is cross-linked to give a
      species that has an apparent molecular mass of a GGH-ecotin dimer with no
      observable protein degradation. The cross-linking reaction occurs between two
      ecotin proteins in a dimer complex. Furthermore, GGH-ecotin can be cross-linked
      to a serine protease target, trypsin, and the reaction is specific for proteins
      that interact with ecotin. The cross-linking reaction has been carried out on
      small peptides, and the reaction products have been analyzed by matrix-assisted
      laser desorption/ionization mass spectrometry. The target of the reaction is
      tyrosine, and the product is bityrosyl cross-links. The yield of the cross
      linking is on the order of 15%. However, the reaction efficiency can be increased
      4-fold by a single amino acid substitution in the carboxy terminus of ecotin that
      places an engineered tyrosine within 5 A of a naturally occurring tyrosine. This
      cross-linking methodology allows for the protein cross-linking reagent to be
      encoded for at the DNA level, thus circumventing the need for posttranslational
      modification.

PMID- 9521760
TI  - Predominant interactions between mu-conotoxin Arg-13 and the skeletal muscle Na+
      channel localized by mutant cycle analysis.
AB  - High-affinity mu-conotoxin block of skeletal muscle Na+ channels depends on an
      arginine at position 13 (Arg-13). To understand both the mechanism of toxin
      interaction and the general structure of its binding site in the channel mouth,
      we examined by thermodynamic mutant cycle analysis the interaction between the
      critical Arg-13 and amino acid residues known to be in the channel's outer
      vestibule. Arg-13 interacts specifically with domain II Glu-758 with energy of
      about -3.0 kcal/mol, including both electrostatic and nonelectrostatic
      components, and with Glu-403 with energy of about -2.0 kcal/mol. Interactions
      with the other charged residues in the outer vestibule were shown to be almost
      entirely electrostatic, because these interactions were maintained when Arg-13
      was replaced by lysine. These results place the bound Arg-13 at the channel mouth
      adjacent to the P (pore) loops of domains I and II. Distance estimates based on
      interaction energies suggest that the charged vestibule residues are in relative
      positions similar to those of the Lipkind-Fozzard vestibule model [Lipkind, G.
      M., and Fozzard, H. A. (1994) Biophys. J. 66, 1-13]. Kinetic analysis suggests
      that Arg-13 interactions are partially formed in the ligand-channel transition
      state.

PMID- 9521761
TI  - Silent nucleotide substitution in the sterol 27-hydroxylase gene (CYP 27) leads
      to alternative pre-mRNA splicing by activating a cryptic 5' splice site at the
      mutant codon in cerebrotendinous xanthomatosis patients.
AB  - A functionally silent nucleotide substitution of the sterol 27-hydroxylase gene
      (CYP 27), identified in two families with cerebrotendinous xanthomatosis (CTX),
      was confirmed to cause alternative pre-mRNA splicing of the gene. Full-length RT
      PCR analysis of the CYP 27 gene in a patient from one of the CTX families
      revealed one major and an additional faint band. Sequence analysis of the cloned
      RT-PCR product showed three species of cDNA: 3' terminal 13 bp of exon 2 deleted
      cDNA, exon 2 skipped cDNA, and full-length cDNA with a functionally silent G to T
      mutation at codon 112 (GGG 112Gly to GGT 112Gly). Only a single base change was
      identified by genomic DNA sequence analysis of the CYP 27 gene in the patient: T
      replaced G at the third position of codon 112, 13 bp upstream from the 3'
      terminus of exon 2. Transfection of constructed minigenes, with or without the
      mutation, confirmed that this silent mutation resulted in alternative pre-mRNA
      splicing by activating a cryptic 5' splice site around the mutant codon. The
      mutation was also identified in two patients from another CTX family, with a
      compound heterozygous pattern of A for G substitution at codon 372, a mutation
      reported previously by our group. The results elucidate a novel molecular basis
      for the CTX and suggest the significance of a silent nucleotide substitution with
      regard to pre-RNA splicing.

PMID- 9521762
TI  - Crystal structures of substrates and products bound to the phosphoglycerate
      kinase active site reveal the catalytic mechanism.
AB  - Phosphoglycerate kinase (PGK) catalyzes the reversible phosphoryl transfer
      between 1,3-bisphosphoglycerate and ADP to form 3-phosphoglycerate and ATP in the
      presence of magnesium. The detailed positions of the substrates during catalysis
      have been a long-standing puzzle due to the major conformational changes required
      for active site formation. Here we report the refined closed form Trypanosoma
      brucei PGK ternary complex at an improved resolution of 2.5 A, together with the
      crystal structure of closed form T. brucei PGK in complex with the nucleotide
      analogue AMP-PNP. In the 180 000 Da asymmetric unit of the ternary complex, four
      closed form PGK molecules appear to be arranged as two asymmetric dimers. Quite
      surprisingly, each dimer is comprised of one 3-phosphoglycerate. MgADP.PGK
      ternary complex and one Pi.MgADP.PGK pseudoternary complex. The substrates in the
      ternary complex are bound in a fashion nearly identical to that in open form PGK,
      but a 30 degrees hinge bending conformational change has brought them together
      and in-line for catalysis. The pseudoternary complex subunits exhibit a similar
      hinge closure but contain, instead of 3-phosphoglycerate, a single phosphate
      molecule bound in the active site. This phosphate binds to a site expected for
      the 1-position phosphate of 1,3-bisphosphoglycerate, hence providing information
      for the binding mode for this chemically unstable substrate. The structure of the
      binary PGK.MgAMP-PNP complex indicates the binding mode for MgATP. An examination
      of the interactions made by the transferring phosphate groups of the substrate,
      1, 3-bisphosphoglycerate, and the product, ATP, reveals that in each case only
      two of the three nonbridging phosphate oxygens are stabilized by hydrogen bonds.
      In contrast, a model of the transition state phosphoryl group based on all
      available structural data reveals active site stabilization of all three
      negatively charged phosphoryl oxygens. These structural models provide insight
      into the nature of the phosphoryl-transfer reaction catalyzed by PGK and related
      enzymes.

PMID- 9521763
TI  - Mutation and modeling analysis of the Saccharomyces cerevisiae Swi6 ankyrin
      repeats.
AB  - The Swi4-Swi6 family of transcription factors confers G1/S specific transcription
      in budding and fission yeast. These proteins contain four ankyrin repeats, which
      are present in a large number of functionally diverse proteins and have been
      shown to be important for protein-protein interaction. However, no specific
      sequence has been identified that is diagnostic of an ankyrin repeat-interacting
      protein. To determine the function of the ankyrin repeats of Swi6, we generated
      both random and site-directed mutations within the ankyrin repeat domain of Swi6
      and assayed the transcriptional function of these mutant swi6 alleles. We found
      six single mutations, scattered within the first and the fourth repeats, that
      generate a temperature-sensitive Swi6 protein. In addition, we found that alanine
      substitutions for the most conserved residues in each repeat were highly
      deleterious and also confer temperature sensitivity. Most of these swi6 alleles
      are able to form ternary complexes with Swi4 and DNA, but these complexes display
      reduced mobility in band-shift gels, suggesting a dramatic conformational change.
      We have modeled the ankyrin repeats of Swi6 using the coordinates derived for
      53BP2 and find that, despite its low level of sequence conservation, these
      modeling studies and our mutation data are consistent with Swi6 having a
      structure very similar to that of 53BP2. Moreover, all but one of our single
      mutants and all of the site-directed mutants disrupt critical structural features
      of the predicted folding pattern of these repeats. We conclude that the ankyrin
      repeats play a major structural role in Swi6. Ankyrin repeats are unlikely to
      have inherent protein or DNA binding properties. However, they form a
      characteristic and stable structure with surfaces that may be tailored for many
      different macromolecular interactions.

PMID- 9521765
TI  - Fourier transform infrared analysis of the interaction of azide with the active
      site of oxidized and reduced bovine Cu,Zn superoxide dismutase.
AB  - Binding of azide to the native and arginine-modified bovine Cu,Zn superoxide
      dismutase in the oxidized and reduced form and to the copper-free derivative has
      been investigated by Fourier transform infrared spectroscopy. The antisymmetric
      stretching band of the azide is shifted to higher energy upon coordination to the
      copper atom of the oxidized form of the native enzyme. Similar spectral changes
      occur upon interaction of the anion with the Cu-diethylenetriamine model
      compound. On the other hand, interaction of azide with the native reduced form of
      the enzyme results in a band shift toward lower energy with respect to the free
      anion band. The same shift is observed after reaction of the azide with free
      lysine or arginine but not when it is reacted with other amino acid residues. The
      antisymmetric band of the azide is not perturbed by addition of the reduced
      arginine-modified enzyme; it is likely shifted toward higher energy upon addition
      of oxidized arginine-modified enzyme while it is again shifted toward lower
      energy in the presence of the copper-free derivative of the unmodified enzyme. It
      is concluded that azide does not directly coordinate to the copper in the reduced
      form of Cu,Zn superoxide dismutase but it remains in the active-site pocket in
      electrostatic interaction with the guanidinium group of Arg141, which is an
      invariant residue in this class of enzymes.

PMID- 9521764
TI  - Opiate analgesics' dual role in firefly luciferase activity.
AB  - The effects of three opiate analgesics, isolated from opium, on the firefly
      luciferase enzyme have been studied. Morphine (MN), 6-acetylmorphine (MAM), and
      diacetylmorphine (DAM) inhibited the enzyme activity at different levels. At
      lower concentrations, MN and MAM enhanced enzyme activity, effecting inhibition
      at higher concentrations. However, DAM inhibited the enzyme activity at all
      concentrations investigated. The stimulating activity of MN and MAM is attributed
      to the hydrophilic interaction of the proton donor-acceptor type with the polar
      regions of the luciferase located outside the binding pocket of the active site.
      The inhibition at higher concentrations of MN and MAM and at all concentrations
      of DAM is found to be competitive in nature, with the analgesics competing for
      the binding of the enzyme's natural substrate luciferin. The binding site of the
      luciferase could accommodate only one analgesic molecule. Binding constants
      determined from bioluminescence studies showed that the inhibitor binding site is
      hydrophobic in nature. The inhibition constants of analgesics are in the order MN
      > MAM > DAM. The greater binding of DAM to luciferase is attributed to its
      ability to form a ground state complex with ATP and greater hydrophobicity. At
      higher concentrations of ATP, the binding constants increased. The results
      obtained are explained assuming that the firefly luciferase acts as a subtype mu
      opioid receptor model.

PMID- 9521766
TI  - Kinetic analysis of zinc ligand mutants of mammalian protein farnesyltransferase.
AB  - Protein farnesyltransferase (FTase) is a zinc metalloenzyme that catalyzes the
      prenylation of several proteins that are important in cellular regulatory events.
      A specific residue of FTase, Cys299 in the beta subunit previously identified as
      essential for zinc binding and catalysis, had been tentatively assigned as one of
      the zinc ligands. This assignment was subsequently confirmed in the X-ray
      structure of FTase, which also identified two additional residues, Asp297 and
      His362 in the beta subunit, as the remaining protein-derived metal ligands. To
      more fully explore the role of zinc in the catalytic mechanism of FTase, site
      directed mutagenesis was performed on these two zinc ligands. Although the
      abilities of all the mutants to bind the farnesyl diphosphate substrate were
      similar to that of the wild-type enzyme, all the mutants displayed markedly
      reduced enzymatic activities and zinc affinities. Steady-state and pre-steady
      state kinetic analyses of the residual activities indicated that the rate
      limiting step changed from product release in the wild-type enzyme to the
      chemical step of product formation for three of the mutant enzymes. Additionally,
      single-turnover experiments indicated that the greatest effect of alteration of
      zinc ligands for all the mutants was on the product formation step, this being
      reduced 10(3)-10(5)-fold in the mutant forms compared to the wild-type enzyme.
      These results confirm a critical involvement of the zinc in catalysis by FTase
      and support a model in which the metal ion is directly involved in the chemical
      step of the enzymatic reaction.

PMID- 9521767
TI  - Substrate specificity of mammalian prenyl protein-specific endoprotease activity.
AB  - We have previously identified proteolytic activity in rat liver microsomes that
      cleaves an intact tripeptide, VIS, from S-farnesylated-CVIS tetrapeptide. This
      enzymatic activity, termed prenyl protein-specific endoprotease (PPEP) activity,
      has been solubilized in CHAPS and purified 5-fold. To probe the peptide
      recognition features of PPEP activity, 64 tripeptides [N-acetyl-C(S
      farnesyl)a1a2] were prepared and tested as competitive inhibitors of PPEP
      activity-catalyzed hydrolysis of N-acetyl-C(S-farnesyl)VI[3H]S. It was found that
      PPEP activity prefers large hydrophobic residues in the a1 and a2 positions. A
      subset of N-acetyl-C(S-farnesyl)a1a2 peptides were prepared in radiolabeled form,
      and it was found that PPEP activity preferences for these substrates correlated
      well in most cases with the inhibition data. The exception is that R in the a1
      position does not prevent binding of peptide to PPEP activity, but such peptides
      are poor substrates. The anionic residue D in the a2 position is not tolerated by
      PPEP activity. Five farnesylated radiolabeled tetrapeptides, Ac-C(F)FM[3H]L, Ac
      C(F)LI[3H]L, Ac-C(F)LL[3H]L, Ac-C(F)LM[3H]L, and Ac-C(F)VI[3H]L were prepared,
      and PPEP activity kinetic studies revealed that they are good substrates and show
      comparable KM values (2.2-13.5 microM). Ac-C(F)RL[3H]S is a poor substrate. The
      reported peptide binding preferences of PPEP activity should be useful in
      designing compounds that block the C-terminal proteolysis of prenylated proteins.
      Nonprenylated peptides do not bind to PPEP activity, and replacement of the
      farnesyl group with ann-pentadecyl group modestly reduces binding. Peptide
      membrane partitioning studies were used together with theoretical arguments to
      fully understand the substrate specificity of PPEP activity toward these
      compounds.

PMID- 9521768
TI  - Specificity of alcohol dehydrogenases for sulfoxides.
AB  - Sulfoxides inhibit horse liver alcohol dehydrogenase (EqADH) by binding to the
      enzyme-NADH complex. X-ray crystallography suggests that sulfoxides make a cation
      pi interaction with the benzene ring of Phe-93 [Cho et al. (1997) Biochemistry
      36, 382-389]. Structure-function relationships were examined with seven different
      sulfoxides binding to five human enzymes (alpha, beta1, gamma2, pi, and sigma)
      and three mutated forms of the horse enzyme. The human gamma2 enzyme, EqADH, and
      EqADH with Phe-93 replaced with Trp were selectively and strongly inhibited (Ki
      </= 1 microM) by the 3-butyl or hexyl derivatives of thiolane 1-oxide. The other
      human enzymes (all with Thr-48) and EqADH with Ser-48 substituted with Thr had
      relatively lower affinities for the thiolane 1-oxides due to close contact of the
      methyl group of Thr-48 with a carbon adjacent to the sulfoxide sulfur. EqADH
      binds the S isomers of 3-butylthiolane 1-oxides, hexyl methyl sulfoxide, and
      phenyl methyl sulfoxide more tightly than the R isomers, but EqADH with Phe-93
      substituted with Ala and the human alpha enzyme (with Ala-93) prefer (R)-phenyl
      methyl sulfoxide, apparently because the phenyl ring fits into the space near
      residue 93. EqADH and the enzymes with Phe-93 replaced with Ala or Trp had
      similar affinities for sulfoxides, indicating that the contribution of the cation
      pi interaction to binding is small or compensated for by altered interactions. Ab
      initio calculations also suggest that the interaction of a sulfoxide with benzene
      is relatively weak.

PMID- 9521769
TI  - Regeneration of three-disulfide mutants of bovine pancreatic ribonuclease A
      missing the 65-72 disulfide bond: characterization of a minor folding pathway of
      ribonuclease A and kinetic roles of Cys65 and Cys72.
AB  - The oxidative regeneration pathways of two three-disulfide mutants of bovine
      pancreatic ribonuclease A (RNase A) missing the 65-72 disulfide bond, [C65S,C72S]
      and [C65A,C72A], have been studied by using oxidized dithiothreitol (DTTox) as an
      oxidizing agent and 2-aminoethylmethanethiosulfonate (AEMTS) as a thiol-blocking
      agent at 25 degrees C and pH 8.0. These mutants are analogues of the des-[65-72]
      intermediate, which is one of the two major three-disulfide intermediates that
      follow after the transition states in the regeneration pathways of wild-type
      RNase A [Rothwarf, D. M., Li, Y.-J., and Scheraga, H. A. (1998) Biochemistry 37,
      3760-3766, 3767-3776.]. Both mutants folded through the same pathway but at a
      rate lower than that of the wild-type protein. The major rate-determining step in
      the regeneration of these mutants was determined to be the oxidation from the two
      disulfide intermediates (2S) to the post-transition-state three-disulfide
      intermediate (3S*), suggesting the existence of a minor oxidation pathway (2S -->
      3S*, where 3S* is des-[65-72]) in the regeneration of the wild-type protein, in
      addition to one of the two major disulfide-rearrangement pathways (3S --> des-[65
      72]). The regeneration intermediates of these mutants (R, 1S, 2S, and 3S)
      participate in a steady state with a kinetic behavior resembling that of the wild
      type protein. However, the apparent equilibrium constants () in the steady state,
      averaged with statistical factors for these mutants, are significantly smaller
      than those for the wild-type protein, indicating that the intermediates in the
      regeneration of the mutants are relatively less stable by 0.32 kcal/mol. This
      difference is due to the decrease in the average rate constants for
      intramolecular disulfide-bond formation () for the mutant proteins. Loop entropy
      calculations indicate that the increase in the average length of all possible
      disulfide loops of the mutants due to the replacement of Cys65 and Cys72 is not
      sufficient to account for the observed reduction of the values of for the
      mutants. Therefore, it is the removal of energetic factors (arising from the loss
      of the 65-72 disulfide loop) that leads to deceleration of the regeneration of
      the mutant proteins. The formation of the 65-72 disulfide loop in the
      regeneration of wild-type RNase A appears to facilitate the subsequent folding
      events.

PMID- 9521770
TI  - Identification of histidine 105 in the beta1 subunit of soluble guanylate cyclase
      as the heme proximal ligand.
AB  - Soluble guanylate cyclase isolated from bovine and rat lung is a heterodimeric
      hemoprotein composed of alpha1 and beta1 subunits. The heme binding region has
      been localized to residues 1-385 of the beta1 subunit [beta1(1-385)], while the
      catalytic site(s) have been localized to the C-terminal region of sGC. There are
      four conserved histidine residues in the heme binding region of sGC. H220 and
      H346 are conserved among all known sGC subunits (alpha and beta), while H105 and
      H134 are conserved only in the beta subunits (beta1 and beta2). Site-directed
      mutagenesis was used to individually change each of the conserved histidines in
      sGC beta1(1-385) to alanine or glycine, and the resulting mutants were expressed
      in E. coli. All of the mutants except for H105A and H105G had heme bound as
      isolated. Imidazole (Im) was able to rescue heme binding to H105G when added to
      the growth medium and purification buffers. The heme in H105G isolated in the
      presence of imidazole [H105G(Im)] was ferric and a mixture of 5-coordinate, high
      spin and 6-coordinate, low-spin complexes. After reduction, the ferrous heme in
      H105G(Im) was 5-coordinate, high-spin as indicated by resonance Raman
      spectroscopy. When imidazole in H105G(Im) was exchanged with N-methylimidazole
      (MeIm), the Fe-N(Im/MeIm) stretching frequency was shifted from 221 to 212 cm-1.
      A shift of this magnitude is expected when the ligand is directly coordinated to
      the heme iron. All of the data are consistent with the conclusion that H105 in
      the beta1 subunit is the heme proximal ligand.

PMID- 9521771
TI  - Retroviral envelope glycoprotein processing: structural investigation of the
      cleavage site.
AB  - Proteolytic activation of retroviral envelope glycoprotein precursors occurs at
      the carboxyl side of a consensus motif consisting of the amino acid sequence
      (Arg/Lys)-Xaa-(Arg/Lys)-Arg. Synthetic peptides spanning the processing sites of
      HIV-1/2 and SIV glycoprotein precursors were examined for their ability to be
      cleaved by the subtilisin-like endoproteases kexin and furin. To determine the
      potential role of secondary structure on proteolytic activation, we examined the
      secondary structure of synthetic peptides by circular dichroism and NMR
      spectroscopy. The results indicate that (i) the peptides were correctly cleaved
      by kexin and furin and therefore could be used as specific substrates for the
      purification and characterization of the lymphocyte endoprotease(s) responsible
      for proteolytic processing of precursors; (ii) the regions surrounding the
      cleavage sites could be characterized by their flexibility in aqueous solutions.
      However, a loop has been shown to be a determinant for the specificity of the
      interaction between the enzyme and its substrate as determined by molecular
      modeling. Furthermore, we determine and propose a possible structure of the
      cleavage site which fits to the active site of the modeled furin.

PMID- 9521772
TI  - Structural basis for specificity of retroviral proteases.
AB  - The Rous sarcoma virus (RSV) protease S9 variant has been engineered to exhibit
      high affinity for HIV-1 protease substrates and inhibitors in order to verify the
      residues deduced to be critical for the specificity differences. The variant has
      9 substitutions (S38T, I42D, I44V, M73V, A100L, V104T, R105P, G106V, and S107N)
      of structurally equivalent residues from HIV-1 protease. Unlike the wild-type
      enzyme, RSV S9 protease hydrolyzes peptides representing the HIV-1 protease
      polyprotein cleavage sites. The crystal structure of RSV S9 protease with the
      inhibitor, Arg-Val-Leu-r-Phe-Glu-Ala-Nle-NH2, a reduced peptide analogue of the
      HIV-1 CA-p2 cleavage site, has been refined to an R factor of 0.175 at 2.4-A
      resolution. The structure shows flap residues that were not visible in the
      previous crystal structure of unliganded wild-type enzyme. Flap residues 64-76
      are structurally similar to residues 47-59 of HIV-1 protease. However, residues
      61-63 form unique loops at the base of the flaps. Mutational analysis indicates
      that these loop residues are essential for catalytic activity. Side chains of
      flap residues His 65 and Gln 63' make hydrogen bond interactions with the
      inhibitor P3 amide and P4' carbonyl oxygen, respectively. Other interactions of
      RSV S9 protease with the CA-p2 analogue are very similar to those observed in the
      crystal structure of HIV-1 protease with the same inhibitor. This is the first
      crystal structure of an avian retroviral protease in complex with an inhibitor,
      and it verifies our knowledge of the molecular basis for specificity differences
      between RSV and HIV-1 proteases.

PMID- 9521773
TI  - Glycosaminoglycans bind to homologous cardiotoxins with different specificity.
AB  - We have reported that some cardiotoxins (CTXs), homologous basic polypeptides of
      cobra venom, bind strongly to heparin. Herein we show that CTXs from spitting
      cobra venom bind avidly to chondroitin-6-sulfate (CS6) and dermatan sulfate (DS),
      the glycosaminoglycans (GAGs) abounding in the cornea and elsewhere. We compared
      the binding strength of Tgamma, a major component of spitting cobra, Naja
      nigricollis, venom with that of CTX A3, a major component of Naja atra venom to
      various GAGs including CS6, chondroitin-4-sulfate (CS4), DS, keratan sulfate
      (KS), hyaluronan (HYA), and heparin. The binding strength of Tgamma followed the
      order CS6 > KS > HYA > DS > CS4 > heparin, whereas that of CTX A3 was heparin >
      KS > CS4 > DS > CS6 > HYA. The binding specificity displayed by different CTXs
      toward GAGs is impressive, given the high homology among CTXs and among GAGs.
      Strong binding of Tgamma to CS6, rather than to the highly anionic and versatile
      cousin, heparin, implies specific interaction with CS6. Heparin, at high
      concentration, displaced CS6 from CS6-Tgamma and CS6-A3 complexes. We also show
      that corneal CS/DS likely allow Tgamma to bind to corneal epithelium. CTXs of
      spitting cobra venom are known to cause corneal opacity and/or blindness. Taken
      together with these observations, our results suggest that corneal CS/DS play a
      role in the action of CTX in the eye. Most importantly, the present results
      establish CTXs as cationic, readily available, avidly binding ligands of CS/DS.

PMID- 9521774
TI  - Mode of action of site-directed irreversible folate analogue inhibitors of
      thymidylate synthase.
AB  - 5,8-Dideazafolate analogues are tight binding but not irreversible inhibitors of
      thymidylate synthase (TS). However, when a chloroacetyl (ClAc) group is
      substituted at the N10-position of 2-desamino-2-methyl-5,8-dideazafolate (DMDDF),
      the resulting compound, ClAc-DMDDF, although still a reversible inhibitor (KI =
      3.4 x 10(-3) M), gradually inactivates thyA-TS irreversibly at a rate of 0.37 min
      1. The corresponding iodoacetyl derivative alkylated the enzyme somewhat slower
      (k3 = 0.15 min-1 ) than ClAc-DMDDF but was bound more tightly (KI = 1.4 x 10(-5)
      M), resulting in a second-order rate constant (k3/KI) of inactivation that was
      100-fold greater than that of ClAc-DMDDF. A tryptic digest of the ClAc-DMDDF
      inactivated enzyme yielded a peptide on HPLC, which revealed that cysteine-146,
      the residue at the active site that is intimately involved in the catalytic
      process, had reacted with ClAc-DMDDF to form a covalent bond. This derivative was
      confirmed indirectly by Edman analysis and more directly by mass spectrometry.
      Deoxyuridine 5'-monophosphate, a substrate in the catalytic reaction, protected
      against inactivation. Similar to previously described Lactobacillus casei TS
      inhibition studies with sulfhydryl reagents [Galivan, J., Noonan, J., and Maley,
      F. (1977) Arch. Biochem. Biophys. 184, 336-345], the kinetics of inhibition
      suggested that complete inhibition occurs on reaction of only one of the two
      active site cysteines, although sequence and amino acid analysis revealed that
      iodoacetate and ClAc-DMDDF had reacted with both active site cysteines. These
      studies demonstrate that a sulfhydryl reactive compound that is directed to the
      folate binding site of TS may diffuse to the active site cysteine, and form a
      covalent bond with this residue. How this inhibition comes about is suggested in
      a stereoscopic view of the ligand when modeled to the known crystal structure of
      Escherichia coli TS.

PMID- 9521775
TI  - Fundamental metabolic differences between hepatocytes and islet beta-cells
      revealed by glucokinase overexpression.
AB  - Adenovirus-mediated overexpression of the glucose phosphorylating enzyme
      glucokinase causes large changes in glycolytic flux and glucose storage in
      isolated rat hepatocytes, but not in pancreatic islets. We have used the well
      differentiated insulinoma cell line INS-1 to investigate the basis for these
      apparent cell-type specific differences. We find that 2- or 5-[3H]glucose usage
      is increased at low (</=5 mM) but not high glucose concentrations in INS-1 cells
      treated with a recombinant adenovirus containing the glucokinase cDNA (AdCMV
      GKI), while glucose usage is increased at both low and high glucose
      concentrations in similarly treated hepatocytes. Utilization of 2-[3H]glucose in
      INS-1 cells is suppressed in glucokinase overexpressing INS-1 cells in a rapid,
      glucose concentration-dependent, and reversible fashion, while such regulation is
      largely absent in hepatocytes. Levels of hexose phosphates (glucose-6-phosphate,
      fructose-6-phosphate, and fructose-1,6-bisphosphate) were profoundly and rapidly
      elevated following the switch to high glucose in either AdCMV-GKI-treated INS-1
      cells or hepatocytes relative to controls. In contrast, triose phosphate levels
      (glyceraldehyde-3-phosphate + dihydroxyacetone phosphate) were much higher in
      AdCMV-GKI-treated INS-1 cells than in similarly treated hepatocytes, suggesting
      limited flux throught the glyceraldehyde-3-phosphate dehydrogenase (G3PDH) step
      in the former cells. Hepatocytes were found to contain approximately 62 times
      more lactate dehydrogenase (LDH) activity than INS-1 cells, and this was
      reflected in a 3-fold increase in lactate production in AdCMV-GKI-treated
      hepatocytes relative to similarly treated INS-1 cells. Since the amounts of G3PDH
      activity in INS-1 and hepatocyte extracts are similar, we suggest that flux
      through this step in INS-1 cells is limited by failure to regenerate NAD in the
      LDH reaction and that a fundamental difference between hepatocytes and islet beta
      cells is the limited capacity of the latter to metabolize glycolytic
      intermediates beyond the G3PDH step.

PMID- 9521777
TI  - Mechanism of phosphatidylinositol-specific phospholipase C: a unified view of the
      mechanism of catalysis.
AB  - The mechanism of phosphatidylinositol-specific phospholipase C (PI-PLC) has been
      suggested to resemble that of ribonuclease A. The goal of this work is to
      rigorously evaluate the mechanism of PI-PLC from Bacillus thuringiensis by
      examining the functional and structural roles of His-32 and His-82, along with
      the two nearby residues Asp-274 and Asp-33 (which form a hydrogen bond with His
      32 and His-82, respectively), using site-directed mutagenesis. In all, twelve
      mutants were constructed, which, except D274E, showed little structural
      perturbation on the basis of 1D NMR and 2D NOESY analyses. The H32A, H32N, H32Q,
      H82A, H82N, H82Q, H82D, and D274A mutants showed a 10(4)-10(5)-fold decrease in
      specific activity toward phosphatidylinositol; the D274N, D33A, and D33N mutants
      retained 0. 1-1% activity, whereas the D274E mutant retained 13% activity. Steady
      state kinetic analysis of mutants using (2R)-1, 2-dipalmitoyloxypropane-3
      (thiophospho-1d-myo-inositol) (DPsPI) as a substrate generally agreed well with
      the specific activity toward phosphatidylinositol. The results suggest a
      mechanism in which His-32 functions as a general base to abstract the proton from
      2-OH and facilitates the attack of the deprotonated 2-oxygen on the phosphorus
      atom. This general base function is augmented by the carboxylate group of Asp-274
      which forms a diad with His-32. The H82A and D33A mutants showed an unusually
      high activity with substrates featuring low pKa leaving groups, such as DPsPI and
      p-nitrophenyl inositol phosphate (NPIPs). These results suggest that His-82
      functions as the general acid with assistance from Asp-33, facilitating the
      departure of the leaving group by protonation of the glycerol O3 oxygen. The
      Bronsted coefficients obtained for the WT and the D33N mutant indicate a high
      degree of proton transfer to the leaving group and further underscore the
      "helper" function of Asp-33. The complete mechanism also includes activation of
      the phosphate group toward nucleophilic attack by a hydrogen bond between Arg-69
      and a nonbridging oxygen atom. The overall mechanism can be described as
      "complex" general acid-general base since three elements are required for
      efficient catalysis.

PMID- 9521776
TI  - Electrospray ionization mass spectrometric analyses of phospholipids from rat and
      human pancreatic islets and subcellular membranes: comparison to other tissues
      and implications for membrane fusion in insulin exocytosis.
AB  - Glucose-induced insulin secretion from pancreatic islets involves hydrolysis of
      arachidonic acid from phospholipids as an intermediary event. Accumulation of
      nonesterified arachidonate in islet membranes may influence both ion fluxes that
      trigger insulin secretion and fusion of secretory granule and plasma membranes.
      Recent findings indicate that plasmenylethanolamine species may also participate
      in fusion of such membranes, but high-performance liquid chromatographic (HPLC)
      and gas chromatographic/mass spectrometric (GC/MS) analyses of islet secretory
      granule phospholipids suggested that they contain little plasmenylethanolamine.
      Here, electrospray ionization mass spectrometry (ESI/MS) of intact phospholipid
      molecules is used to demonstrate that the most prominent components of all major
      glycerophospholipid headgroup classes in islets are arachidonate-containing
      species. Such species contribute the majority of the ESI/MS negative ion current
      from rat and human islet glycerophosphoethanolamine (GPE), and the fraction of
      GPE negative ion current contributed by plasmenylethanolamine species in rat
      islets is higher than that for rat liver or heart and similar to that for brain.
      The most prominent sn-2 substituent of plasmenylethanolamine species in brain is
      docosahexaenoate and in islets is arachidonate. Arachidonate-containing
      plasmenylethanolamine species are also prominent components of GPE from islet
      secretory granules and plasma membranes. Fusion of islet secretory granule and
      plasma membranes is demonstrated to be catalyzed by cytosolic components from
      insulinoma cells and rat brain with chromatographic similarities to a rabbit
      brain factor that specifically catalyzes fusion of plasmenylethanolamine
      containing membranes.

PMID- 9521778
TI  - Dephosphorylation kinetics of pig kidney Na+,K+-ATPase.
AB  - The kinetics of K+-stimulated dephosphorylation of the Na+,K+-ATPase were
      investigated at pH 7.4, 24 degrees C, and an ATP concentration of 1.0 mM via the
      stopped-flow technique using the fluorescent label RH421. Two different mixing
      procedures were used: (a) premixing with ATP to allow phosphorylation to go to
      completion, followed by mixing with KCl; and (b) simultaneous mixing with ATP and
      KCl. Using mixing procedure (a), the dephosphorylation rate constant of enzyme
      complexed with K+ ions could be determined directly to be </=366 s-1 and the rate
      constant for spontaneous dephosphorylation (without K+) </=60 s-1. The K+
      concentration dependence of the observed reciprocal time constant showed half
      saturation at a K+ concentration of 2.4-2.6 mM with positive cooperativity
      involved in the occupation of the K+ binding sites on the E2P conformation of the
      enzyme. Using mixing procedure (b), it was found that at saturating K+
      concentrations the dephosphorylation of the enzyme is rate-limited by its
      phosphorylation, which occurs with a rate constant of approximately 190 s-1 (1).
      These results show that all reactions occurring after phosphorylation and prior
      to dephosphorylation, i.e., the E1P to E2P conformational transition as well as
      Na+ release and K+ binding steps, must be fast (>190 s-1).

PMID- 9521779
TI  - Mutations in either nucleotide-binding site of P-glycoprotein (Mdr3) prevent
      vanadate trapping of nucleotide at both sites.
AB  - Vanadate trapping of nucleotide and site-directed mutagenesis were used to
      investigate the role of the two nucleotide-binding (NB) sites in the regulation
      of ATP hydrolysis by P-glycoprotein (mouse Mdr3). Mdr3, tagged with a
      hexahistidine tail, was overexpressed in the yeast Pichia pastoris and purified
      to about 90% homogeneity by Ni-affinity chromatography. This protocol yielded
      purified, reconstituted Mdr3 which exhibited high verapamil stimulation of ATPase
      activity with a Vmax of 4.2 micromol min-1 mg-1 and a KM of 0.7 mM, suggesting
      that Mdr3 purified from P. pastoris is highly functional. Point mutations were
      introduced into the core consensus sequence of the Walker A or B motifs in each
      of the two NB sites. The mutants K429R, K1072R (Walker A) and D551N, D1196N
      (Walker B) were functionally impaired and unable to confer cellular resistance to
      the fungicide FK506 in the yeast Saccharomyces cerevisiae. Single and double
      mutants (K429R/K1072R, D551N/D1196N) were expressed in P. pastoris, and the
      effect of these mutations on the ATPase activity of Mdr3 was characterized.
      Purified reconstituted Mdr3 mutants showed no detectable ATPase activity compared
      to proteoliposomes purified from negative controls (<5% of wild-type Mdr3).
      Vanadate readily induced trapping of 8-azido-nucleotide in the wild-type enzyme
      after a short 10 s incubation, and specific photolabeling of Mdr3 after UV
      irradiation. No such vanadate-induced trapping/photolabeling was observed in any
      of the mutants, even after a 60 min trapping period at 37 degrees C. Since
      vanadate trapping with 8-azido-ATP requires hydrolysis of the nucleotide, the
      data suggest that 8-azido-ATP hydrolysis is dramatically impaired in all of the
      mutant proteins (<0.3% activity). These results show that mutations in either NB
      site prevent single turnover and vanadate trapping of nucleotide in the nonmutant
      site. These results further suggest that the two NB sites cannot function
      independently as catalytic sites in the intact molecule. In addition, the N- or C
      terminal NB sites appear functionally indistinguishable, and cooperative
      interactions absolutely required for ATP hydrolysis may originate from both
      sites.

PMID- 9521780
TI  - Groups with polar characteristics can locate at both shallow and deep locations
      in membranes: the behavior of dansyl and related probes.
AB  - To understand the relationship between the chemical structure of polar molecules
      and their membrane location, the behavior of dansyl
      (dimethylaminonaphthalenesulfonyl) and related polar fluorescent probes was
      examined. The depth of these probes in lipid bilayers was determined by parallax
      analysis of fluorescence quenching [Chattopadhyay and London (1987) Biochemistry
      26, 39-45; Abrams & London, Biochemistry (1993) 32, 10826-10831]. Quenching was
      measured for dansyl groups: (1) attached to the polar headgroup of PE, (2) linked
      to an alkyl chain, (3) attached to the end of a fatty acyl chain, and (4)
      attached to the polar headgroup of PE via a spacer group. In all cases, the
      dansyl probes located in the polar headgroup region, 19-21 A from the bilayer
      center. This shows the dansyl group has a strong tendency to seek a shallow
      location in the polar headgroup region. The only exception to this pattern was in
      the case of a dialkylated dansyl, for which two populations were observed. One
      population was at the polar headgroup level, but the second was deeply buried in
      the acyl chain region. To see if the polar sulfonamide group of dansyl influences
      depth, a structurally related probe substituting a thiocarbamoyl linkage,
      dimethylaminonaphthalenethiocarbamoyl (dantyl)-labeled PE, was synthesized.
      Dantyl groups were located deeper than dansyl groups, 13-16 A from the bilayer
      center. There was an even more dramatic difference in depth between dansyl and
      mansyl (methylanilinonaphthalenesulfonyl) derivatives. Mansyl probes, which have
      an extra phenyl group relative to dansyl, were found to locate deeply within the
      acyl chain region of the bilayer (6-7 A from the bilayer center) when attached to
      the polar headgroup of PE. Thus, the membrane location of polar groups depends
      strongly on the details of their chemical structure, and it is possible for a
      polar group to locate both at shallow and deep locations. These results suggest
      the energy to bury a polar moiety in the hydrophobic part of the bilayer is not
      prohibitively high. This contrasts to the behavior of charged groups, which
      appear to be restricted to shallow locations in membranes. In this report, the
      effect of populations at two different depths on the parallax analysis is also
      considered.

PMID- 9521782
TI  - Involvement of two aspartate residues of Rubisco activase in coordination of the
      ATP gamma-phosphate and subunit cooperativity.
AB  - Aspartate residues are involved in coordination of the nucleotide-metal of
      several nucleotide triphosphatases. To examine interactions between Rubisco
      activase and ATP, site-directed mutations were made at two species-invariant
      aspartate residues, D174 and D231. In the absence of the magnesium cofactor, the
      mutant proteins D231R, D174Q, and D174A, but not D174E, bound ATP with higher
      affinity than did wild-type. In the presence of Mg2+, the affinity for ATP of
      D231R was further increased, but was reduced with mutations at D174. Although all
      mutants bound ATP, only D174E aggregated in response to ATP/Mg2+ and retained
      partial ATPase and Rubisco activation activities. In mixing experiments, the
      catalytically competent D174E stimulated wild-type ATPase activity, whereas the
      mutants lacking ATPase activity were inhibitory to wild-type enzyme and prevented
      aggregation. These results are consistent with a mechanism for activase that
      involves ATP-binding, subunit aggregation and ATP hydrolysis as sequential steps
      in the catalytic mechanism. The results also indicated that precise coordination
      of the gamma-phosphate is required for aggregation and depends on D174 and D231.
      To account for the pronounced cooperativity of Rubisco activase subunits, we
      suggest that coordination of the ATP gamma-phosphate may involve participation of
      residues from adjacent subunits.

PMID- 9521781
TI  - Role of the [Fe4S4] cluster in mediating disulfide reduction in spinach
      ferredoxin:thioredoxin reductase.
AB  - Thioredoxin reduction in plant chloroplasts is catalyzed by a unique class of
      disulfide reductases which use a one-electron donor, [Fe2S2]2+,+ ferredoxin, and
      has an active site involving a disulfide in close proximity to a [Fe4S4]2+
      cluster. In this study, spinach ferredoxin:thioredoxin reductase (FTR) reduced
      with stoichiometric amounts of reduced benzyl viologen or frozen under turnover
      conditions in the presence of thioredoxin is shown to exhibit a slowly relaxing S
      = 1/2 resonance (g = 2.11, 2.00, 1.98) identical to that of a modified form of
      the enzyme in which one of the cysteines of the active-site disulfide is
      alkylated with N-ethylmaleimide (NEM-FTR). Hence, in accord with the previous
      proposal [Staples, C.R., Ameyibor, E., Fu, W., Gardet-Salvi, L., Stritt-Etter, A.
      L., Schurmann, P., Knaff, D.B., and Johnson, M.K. (1996) Biochemistry 35, 11425
      11434], NEM-FTR is shown to be a stable analogue of a one-electron-reduced
      enzymatic intermediate. The properties of the Fe-S cluster in NEM-FTR have been
      further investigated by resonance Raman and electron nuclear double resonance
      spectroscopies; the results, taken together with the previous UV-visible
      absorption, variable temperature magnetic circular dichroism, and resonance Raman
      data, indicate the presence of a novel type of [Fe4S4]3+ cluster that is
      coordinated by five cysteinates with little unpaired spin density delocalized
      onto the cluster-associated cysteine of the active-site disulfide. While the
      ligation site of the fifth cysteine remains undefined, the best candidate is a
      cluster bridging sulfide. On the basis of the spectroscopic and redox results,
      mechanistic schemes are proposed for the benzyl viologen-mediated two-electron
      reduction of FTR and the catalytic mechanism of FTR. The catalytic mechanism
      involves novel S-based cluster chemistry to facilitate electron transfer to the
      active-site disulfide resulting in covalent attachment of the electron-transfer
      cysteine and generation of the free interchange cysteine that is required for the
      thiol-disulfide interchange reaction with thioredoxin.

PMID- 9521783
TI  - A triple mutation in the a subunit of the Escherichia coli/Propionigenium
      modestum F1Fo ATPase hybrid causes a switch from Na+ stimulation to Na+
      inhibition.
AB  - Previously we have shown that the Na+-translocating Escherichia coli (F1
      delta)/Propionigenium modestum (Fo+delta) hybrid ATPase acquires a Na+
      independent phenotype by the c subunit double mutation F84L, L87V that is
      reflected by Na+-independent growth of the mutant strain MPC8487 on succinate
      [Kaim, G., and Dimroth, P. (1995) J. Mol. Biol. 253, 726-738]. Here we describe a
      new class of mutants that were obtained by random mutagenesis and screening for
      Na+-independent growth on succinate. All six mutants of the new class contained
      four mutations in the a subunit (S89P, K220R, V264E, I278N). Results from site
      specific mutagenesis revealed that the substitutions K220R, V264E, and I278N were
      sufficient to create the new phenotype. The resulting E. coli mutant strain
      MPA762 could only grow in the absence but not in the presence of Na+ ions on
      succinate minimal medium. This effect of Na+ ions on growth correlated with a Na+
      specific inhibition of the mutant ATPase. The Ki for NaCl was 1. 5 mM at pH 6.5,
      similar to the Km for NaCl in activating the parent hybrid ATPase at this pH. On
      the other hand, activation by Li+ ions was retained in the new mutant ATPase. In
      the absence of Na+ or Li+, the mutant enzyme had the same pH optimum at pH 6.5
      and twice the specific activity as the parent hybrid ATPase. In accordance with
      the kinetic data, the reconstituted mutant ATPase catalyzed H+ or Li+ transport
      but no Na+ transport. These results show for the first time that the coupling ion
      selectivity of F1Fo ATPases is determined by structural elements not only of the
      c subunit but also of the a subunit.

PMID- 9521784
TI  - Effect of four helix bundle topology on heme binding and redox properties.
AB  - We have designed two alternative four helix bundle protein scaffold topologies
      for maquette construction to examine the effect of helix orientation on the heme
      binding and redox properties of our prototype heme protein maquette, (alpha-SS
      alpha)2, previously described as H10H24 [Robertson, D. E., Farid, R. S., Moser,
      C. C., Mulholland, S. E., Pidikiti, R., Lear, J. D., Wand, A. J., DeGrado, W. F.,
      and Dutton, P. L. (1994) Nature 368, 425]. Conversion of the disulfide-bridged di
      alpha-helical monomer of (alpha-SS-alpha)2 into a single polypeptide chain
      results in topological reorientation of the helix dipoles and side chains within
      a 62 amino acid helix-loop-helix monomer, (alpha-l-alpha), which self-associates
      to form (alpha-l-alpha)2. Addition of an N-terminal cysteine residue to (alpha-l
      alpha) with subsequent oxidation yields a 126 amino acid single molecule four
      helix bundle, (alpha-l-alpha-SS-alpha-l-alpha). Gel permeation chromatography
      demonstrated that (alpha-SS-alpha)2 and (alpha'-SS-alpha')2, a uniquely
      structured variant of the prototype, as well as (alpha-l-alpha)2 and (alpha'-l
      alpha')2 assemble into distinct four helix bundles as designed, whereas (alpha-l
      alpha-SS-alpha-l-alpha) elutes as a monomeric four alpha-helix bundle. Circular
      dichroism (CD) spectroscopy proves that these peptides are highly alpha-helical,
      and incorporation of four hemes has little effect on the helical content of the
      secondary structure. Four heme dissociation constants were evaluated by UV
      visible spectroscopy and ranged from the 15 nM to 25 microM range for each of the
      peptides. The presence of Cotton effects in the visible CD illustrated that the
      hemes reside within the protein architecture. The equilibrium redox midpoint
      potentials (Em8) of the four bound hemes in each peptide are between -100 and 
      280 mV, as determined by redox potentiometry. The heme affinity and
      spectroelectrochemical properties of the hemes bound to (alpha-l-alpha)2 and
      (alpha-l-alpha-SS-alpha-l-alpha) are similar to those of the prototype, (alpha-SS
      alpha)2, and to bis-histidine ligated b-type cytochromes, regardless of the
      global architectural changes imposed by these topological rearrangements. The
      hydrophobic cores of these peptides support local electrostatic fields which
      result in nativelike heme chromophore properties (spectroscopy, elevated
      reduction potentials, heme-heme charge interaction, and reactivity with exogenous
      diatomics) illustrating the utility of these non-native peptides in the study of
      metalloproteins.

PMID- 9521785
TI  - The biochemistry of hemolysin toxin activation: characterization of HlyC, an
      internal protein acyltransferase.
AB  - Hemolysin toxin produced and secreted by pathogenic Escherichia coli is one of a
      family of cytolytic, structurally homologous protein toxins known as RTX (repeats
      in toxin) toxins. RTX toxins are products of a gene cluster, CABD. The A gene
      product, nontoxic hemolysin (proHlyA), is made toxic by posttranslational fatty
      acylation of two internal lysine residues. HlyC, the C gene product, is essential
      for acylation, and acyl-acyl carrier protein (ACP) is the acyl donor. HlyB and
      HlyD are involved in secretion of the toxin. ProHlyA and HlyC were separately
      subcloned, expressed, and purified, and acyl-ACPs with diverse radioactive acyl
      groups were synthesized. With these proteins, the conversion of proHlyA to HlyA
      by acyl transfer was assayed. Acyl-ACP was the obligate acyl donor. Acyl transfer
      was catalyzed by HlyC monomer, and an acyl-enzyme intermediate was shown.
      Reaction was inhibited by ACPSH but not by fatty acid or fatty-acyl CoA. Km and
      Vmax for HlyA were 0.94 microM and 7.5 pmol of acyl group transferred/min,
      respectively; Km and Vmax for myristoyl-ACP were 0.48 microM and 6.9 pmol/min.
      The kinetic parameters of different acyl-ACPs resembled a competitive inhibition
      as acyl group carbon chain length increased; Km's increased while Vmax's remained
      unchanged. The different kinetic efficacies in the acyltransferase reaction of
      the ACPs with different acyl groups contrasted notably with the lytic powers of
      the corresponding acyl-toxins that they generated.

PMID- 9521787
TI  - Induced circular dichroism of benzo[a]pyrene-7,8-dihydrodiol 9,10-epoxide
      stereoisomers covalently bound to deoxyribooligonucleotides used to probe
      equilibrium distribution between groove binding and intercalative adduct
      conformations.
AB  - Binding conformations of single anti-BPDE-N2-dG adducts in oligonucleotides of
      varying base composition have been studied by induced circular dichroism (ICD).
      The sign of the ICD around 350 nm of single-stranded oligonucleotide adducts and
      the sign of an exciton type of CD component at 260 nm in both single strand and
      duplex forms of adducts correlate with the absolute configuration of the
      cyclohexyl moiety of the adduct. Changes in magnitude and sign of the ICD around
      350 nm were observed upon duplex formation. The results show that adducts
      displaying external (minor groove) binding characteristics are associated with a
      significant positive ICD. Conversely, adducts displaying intercalation binding
      characteristics were found to have a positive or negative ICD. The magnitude of
      the ICD is dependent on the sequence context and the particular adduct isomer
      studied. Duplexes with (+)-trans-anti-BPDE-N2-dG in 5'-d(CCTATCGCTATCC) or 5'
      d(CCTATAGATATCC) exhibit a relatively strong positive ICD. In contrast, the
      duplexes with (+)-trans-anti-BPDE-N2-dG in 5'-d(CCTATTGCTATCC) and 5'
      d(CCTATTGTTATCC) display a small positive and negative ICD, respectively, in both
      cases suggesting conformational heterogeneity. Partially complementary duplexes
      (dA, dT, or dG) localized opposite the (+)-trans-anti-BPDE-N2-dG adduct in 5'
      d(CCTATCGCTATCC) or 5'-d(CCTATAGATATCC) also demonstrated negative ICD. These
      results together with light absorption characteristics suggest a preferred
      conformation of intercalation for the mismatched duplexes. Evidence of an
      equilibrium between the external and intercalative adduct conformation is
      provided by the results from the temperature dependence of the near-UV absorption
      and ICD characteristics of (+)-trans-anti-BPDE-N2-dG complex in a 5'
      d(CCTATAGATATCC) duplex.

PMID- 9521788
TI  - Movement of the intermediate and rate determining transition state of barnase on
      the energy landscape with changing temperature.
AB  - Barnase folds cooperatively via an intermediate, followed by a rate-limiting
      transition state. We have probed possible movements of the intermediate and
      transition state on the energy landscape with changing temperature, from the
      temperature dependence of phi-values. These measure interaction energies at the
      level of individual residues. The results suggest that single destabilizing
      mutations can redistribute the structures in each ensemble on the energy
      landscape as the temperature is varied. The results were also analyzed in terms
      of the bulk properties of each ensemble and their movements on the energy
      landscape. These movements can be described in terms of the "new view" or
      equivalently in terms of the classical "Hammond" or "anti-Hammond" effects,
      observed previously for the transition states of barnase at 7.25 M urea and
      chymotrypsin inhibitor 2 (CI2) at 0.3 and 6 M GdmCl. The results presented here
      are under more relevant physiological conditions, free of chemical denaturants.
      The "average" structures of the intermediate and the transition state do not
      appear to move on the energy landscape as the temperature is varied. However,
      there are small rearrangements in the major alpha-helix of the transition state,
      its average structure moving closer to the native state as the temperature is
      increased, in agreement with the Hammond effect observed previously.

PMID- 9521786
TI  - A novel acidophilic RNA motif that recognizes coenzyme A.
AB  - Specific recognition of nucleotide cofactors by RNA may be important in
      engineering new RNA enzymes (ribozymes). Although in vitro selections (SELEX)
      have identified nucleic acid motifs ("aptamers") that bind a variety of adenosine
      cofactors, none of these recognizes coenzyme A (CoA), the primary biological
      cofactor used in acyltransfer reactions. We used SELEX experiments with two
      random RNA pools to identify aptamers that bind CoA. Functional boundary
      determination and extensive comparative sequence analysis (including reselection
      of a mutagenized, circularly permuted RNA) led to the identification of a 52
      nucleotide minimal aptamer ("min52"). The RNA structural motif contains a large
      internal loop with 26 unpaired nucleotides flanked by helices of any base-paired
      sequence. Twenty loop nucleotides are specifically required for binding activity,
      12 of which are derived from the original primer binding sequences. Specificity
      studies with CoA analogues demonstrated that the aptamer recognizes many
      adenosine analogues, including ATP, and that recognition is predominantly through
      the Hoogsteen face of adenine. Binding activity is greatest at acidic pH (optimum
      near 5.0), in low or no monovalent salt, and at high concentrations of either
      Mg2+ or Mn2+. Strong binding activity (86% of maximum) is observed at pH 4.0,
      suggesting that at least some extreme conditions (acidic pH) may be compatible
      with RNA World theories of the origin and early evolution of life. In the
      presence of 10 mM Mg2+, binding is unaffected by the addition of 1 mM Ca2+, but
      it is mildly inhibited by 1 mM Zn2+ or Co2+ or by 0.1 mM Cu2+ or Ni2+. The
      dissociation constant (Kd) for the association of min52 RNA with ATP in solution
      was measured to be 2.4 +/- 0.4 microM under the conditions of the selection and
      0.5 +/- 0.1 microM under optimized conditions. Finally, we show that the selected
      CoA aptamer populations contain other RNAs at low frequencies that preferentially
      recognize intact CoA and are not eluted from the resin by AMP alone.

PMID- 9521790
TI  - Beta-tubulin isotypes purified from bovine brain have different relative
      stabilities.
AB  - The highly conserved nature and tissue specificity of the seven vertebrate beta
      tubulin isotypes provide circumstantial evidence that functional differences
      among isotypes may exist in vivo. Compelling evidence from studies of bovine
      brain beta-isotypes indicated significant conformational and functional
      differences in vitro and implied that these differences could be related to in
      vivo function. A previously uninvestigated parameter of potential importance in
      assessing functional significance is molecular stability. We examined the
      relative stability of alphabetaII and alphabetaIII tubulin dimers purified from
      bovine brain. The use of probes to monitor the exposure of hydrophobic areas and
      sulfhydryls and the loss of colchicine binding, all of which are known to
      accompany tubulin's time-dependent loss of function, showed an acceleration of
      these criteria in alphabetaII relative to alphabetaIII when the isotypes were
      incubated at 37 degrees C. Studies using differential scanning calorimetry
      suggested that unfolding of the isotypes at approximately 60 degrees C and decay
      at 0 degrees C were both highly cooperative. It was also observed that
      alphabetaIII had a higher melting temperature and a larger population of
      molecules retaining tertiary structure after incubation at 0 degrees C for 20 h.
      These studies support the conclusion that alphabetaIII is significantly more
      stable than alphabetaII and raise the possibility that differences in relative
      stabilities of tubulin isotypes may be important in regulating the functional
      properties of microtubules in vivo.

PMID- 9521789
TI  - Topological disposition of Cys 222 in the alpha-subunit of nicotinic
      acetylcholine receptor analyzed by fluorescence-quenching and electron
      paramagnetic resonance measurements.
AB  - The structure of the nicotinic acetylcholine receptor (AChR) has been studied
      using a combination of fluorescence quenching and electron paramagnetic resonance
      (EPR) collision gradient methods. The AChR from Torpedo californica was labeled
      with a fluorescent probe, N-(1-pyrenyl)maleimide, specific for sulfhydryls in a
      hydrophobic environment, under conditions of selective labeling of Cys222 in the
      alpha-subunit. alphaCys222 is located in the postulated M1 transmembrane domain
      and predicted to be at the center of an alpha-helical secondary structure. The
      spatial disposition of the acetylcholine receptor-bound pyrene with respect to
      the membrane bilayer was assessed by fluorescence quenching measurements.
      Quenching of pyrene fluorescence by spin-labeled fatty acids with the doxyl group
      at positions C-5 and C-12 revealed that the former was more effective, suggesting
      that the fluorophore is located closer to the membrane-water interface than to
      the hydrophobic interior. Power saturation EPR spectroscopy was also used to
      examine the effect of molecular oxygen and water-soluble paramagnetic reagents on
      the saturation behavior of a nitroxide spin label, which was specifically
      attached to the same alphaCys222 residue. Using the gradients of these
      paramagnetic reagents through the membrane-solution interface, the distance for
      the nitroxide derivative from the membrane-solution interface was measured to be
      approximately 7 A from the headgroup region of the phospholipid bilayer, in
      agreement with fluorescence quenching results. These results suggest that the M1
      transmembrane domain of the AChR probably forms an irregular structure, a beta
      strand, or an alpha-helical structure that may span the membrane in a way
      different from a linear alpha-helix.

PMID- 9521791
TI  - Male advertisement call and female preference in sympatric and allopatric midwife
      toads
AB  - Advertisement calls and female preferences in allopatric populations of midwife
      toads, Alytes obstetricans and A. cisternasiiwere compared with those in a
      sympatric population. These species have simple tonal advertisement calls which
      overlap substantially in frequency and duration. In both species, the duration of
      male advertisement calls did not differ between an allopatric and a sympatric
      population. Playback tests suggested that females in allopatric populations
      preferentially approach low frequency calls and long calls, exerting directional
      selection for larger males and males with longer calls. Female A. cisternasii
      from the sympatric zone did not prefer low frequency calls, which could be made
      by males of A. obstetricansSimilarly, female A. obstetricans from the sympatric
      zone did not preferentially approach long calls, which could be made by A.
      cisternasii males. The differences in female preference between sympatry and
      allopatry follow the expected direction of reproductive character displacement.
      Within each species, female preferences differed clearly between sympatry and
      allopatry while male call characteristics did not.Copyright 1997 The Association
      for the Study of Animal BehaviourCopyright 1997The Association for the Study of
      Animal Behaviour.

PMID- 9521792
TI  - Sexual selection constrained by internal fertilization in the livebearing fish
      Xenotoca eiseni
AB  - Fish of the family Goodeidae have an advanced form of viviparity but males lack a
      specialized copulatory organ. Goodeids show reduced sexual-size dimorphism
      compared with the other livebearing families of the order Cyprinodontiformes. I
      investigated some mechanisms of sexual selection acting on body size in the
      goodeid fish Xenotoca eiseni. Both males and females strongly prefer mates of
      their own size. Comparison of mating activities in pairs with various degrees of
      size difference between males and females showed that matched pairs copulated
      more successfully. Similar mate preference in the two sexes thus appears to be
      the consequence of the primitive method of internal fertilization that requires
      the partners to be exactly synchronized during sperm transfer. Competition for
      access to a female was intense and body size determined the hierarchy in a small
      group. However, unless the size of the female was close to that of the dominant
      male, assortative mate preferences prevailed and the large-male advantage in
      competition was offset. Reduced size dimorphism in X. eiseni and in other
      goodeids may be explained by constraints on the action of sexual selection
      imposed by the need for effective fertilization.Copyright 1997 The Association
      for the Study of Animal BehaviourCopyright 1997The Association for the Study of
      Animal Behaviour.

PMID- 9521793
TI  - Brood division in birds in relation to offspring size: sibling rivalry and
      parental control
AB  - In some altricial birds with biparental care, it is the female, and in others the
      male, that provides more food to the smallest offspring within the brood. Many
      hypotheses have been proposed to account for such puzzling patterns of parental
      care. A parsimonious explanation is that no difference exists between the parents
      in priority of care but that differences arise simply from sibling rivalry, with
      dominant chicks trying to position themselves closest to the parent that provides
      most care (the sibling rivalry hypothesis). A refinement of the idea is that
      parents use the way they approach the chicks to counter selfish offspring and in
      this way control allocation of care (the parental approaching hypothesis). A
      comparison across species suggested that female care of the smallest chick within
      a brood is the ancestral and most common pattern. However, strong variation
      exists within single populations. In one species, the American robin, Turdus
      migratorius the sibling rivalry hypothesis and the parental approaching
      hypothesis were both supported because in broods where males provided more care
      than females, the largest chick was predominantly fed by the male whereas the
      smallest chick was predominantly fed by the female. When the male provided less
      care than the female, an opposite result was found. The same patterns of
      allocation of care also seemed to exist when chicks were quite immobile just
      after having left the nest and when their positions were experimentally
      controlled, suggesting parental control.Copyright 1997 The Association for the
      Study of Animal BehaviourCopyright 1997The Association for the Study of Animal
      Behaviour.

PMID- 9521794
TI  - Courtship feeding in tree crickets increases insemination and female reproductive
      life span
AB  - Courtship feeding in the majority of insects may influence female reproductive
      patterns either directly, through effects of the gift material, or indirectly,
      through correlated effects of prolonged copulation and larger ejaculates. This
      distinction is important because the cause of changes in fecundity may influence
      patterns of the allocation of resources between the sexes, with implications for
      the intensity of sexual selection and magnitude of sexual conflict. I show that
      post-copulatory feeding on the secretions of a gland on the metanotum of male
      Oecanthus nigricornis. Walker correlates with oviposition and affects the number
      of sperm remaining within the spermatophore. Manipulations of gland feeding and
      insemination duration showed that changes in fecundity are due to the gift rather
      than the ejaculate. Metanotal gland feeding increased female fecundity by
      increasing reproductive life span without significantly increasing oviposition
      rate. These changes in reproduction were directly due to the gift itself.
      Although gland feeding was positively correlated with the duration of
      insemination and thus the number of sperm transferred from the spermatophore to
      the female, experimentally prolonging or reducing insemination had no significant
      effect on reproductive life span. Male phenotype was also associated with female
      fecundity but in this case the effect was caused by an increase in the
      oviposition rate of females that mated with relatively large males. Male size had
      no significant effect on female reproductive life span, suggesting that its
      effect is not simply due to a quantitative increase in gift size. Three other
      measures of male phenotype, fluctuating asymmetry, condition (i.e. size
      standardized wet body mass) and age, had no significant effects on female
      reproduction.Copyright 1997 The Association for the Study of Animal
      BehaviourCopyright 1997The Association for the Study of Animal Behaviour.

PMID- 9521795
TI  - Ultraviolet vision and band-colour preferences in female zebra finches,
      Taeniopygia guttata
AB  - Zebra finches have previously been found to have preferences for particular
      colours of both natural and artificial traits among opposite sex conspecifics.
      For example, in some studies female zebra finches preferred males wearing red leg
      bands to orange-banded and unbanded birds and rejected light green-banded males.
      In other studies, females also preferred males with red beaks to orange-beaked
      males. However, several authors have failed to replicate these results. We show
      that females may fail to show a colour preference because of the absence or
      removal of ultraviolet light under experimental conditions. In mate-choice
      trials, females observing males through filters that transmitted ultraviolet
      preferred red-banded males but where females viewed males through ultraviolet
      blocking filters, no such preference was observed. Further investigation revealed
      that the lack of a colour preference when ultraviolet was absent was probably due
      to the change in overall appearance of the bird, rather than the change in
      appearance of the rings themselves. This work highlights the importance of proper
      consider-ation of the sensory capabilities of animals in experimental design,
      particularly with regard to the role of ultraviolet light in avian colour
      perception.Copyright 1997 The Association for the Study of Animal
      BehaviourCopyright 1997The Association for the Study of Animal Behaviour.

PMID- 9521796
TI  - Reproductive synchrony and extra-pair mating strategy in a socially monogamous
      bird, Dendroica petechia
AB  - Depending on the circumstances under which extra-pair mating occurs, theory makes
      opposing predictions about how reproductive synchrony should influence extra-pair
      paternity. This study investigated which sex initiated extra-pair mating in the
      yellow warbler, whether extra-pair behaviour and extra-pair paternity were
      related to reproductive synchrony, and whether synchrony affected the mating
      success of all males equally. Observations and captures of individuals making
      territorial intrusions indicated that males initiated extra-pair mating. Spatial
      patterns of male territorial intrusions and of extra-pair paternity were similar.
      Males' extra-pair activity was reduced when their social partner was fertile.
      More offspring were sired by the extra-pair male when the female nested
      asynchronously with that sire's social mate. Neither population-wide synchrony,
      nor synchrony with neighbours, however, seemed to predict the incidence of extra
      pair parentage or the identity of the sire, indicating factors other than
      synchrony were also important. Males with more breast streaking (a plumage
      ornament) were more successful as extra-pair sires, and were least affected by
      the constraint of synchrony. Larger males were less often cuckolded, and achieved
      extra-pair success mainly when their partner was not fertile. Thus, male yellow
      warblers apparently use different mating tactics depending on their plumage and
      size. More generally, the results suggest how mating strategies are affected by
      which sex initiates extra-pair mating and by the relative contributions of within
      pair and extra-pair paternity to total reproductive success.Copyright 1997 The
      Association for the Study of Animal BehaviourCopyright 1997The Association for
      the Study of Animal Behaviour.

PMID- 9521797
TI  - Seasonal changes in sheltering: effect of light and temperature on diel activity
      in juvenile salmon
AB  - Previous work has shown that juvenile Atlantic salmon, Salmo salar L, are
      predominantly nocturnal during winter (spending the day sheltering in streambed
      refuges) but become active 24 h a day in the summer. Observations of salmon in a
      semi-natural stream revealed how light, temperature and time of year determined
      these activity patterns; we also tested whether the life-history strategy of the
      fish affected diel activity, comparing fish that would migrate to sea the
      following spring with those that would be resident in fresh water for at least an
      additional year. Fish tended to hide at high light levels whenever the water was
      cold but were increasingly likely to emerge as the winter progressed. There were
      significant differences between the two groups of fish: the putative migrants
      sheltered more than the resident group in winter, but this trend was reversed in
      the spring. Reducing the risk of predation in winter may be one of the reasons
      for this seasonal change in behaviour.Copyright 1997 The Association for the
      Study of Animal BehaviourCopyright 1997The Association for the Study of Animal
      Behaviour.

PMID- 9521798
TI  - Associative learning by locusts: pairing of visual cues with consumption of
      protein and carbohydrate
AB  - We investigated whether fifth instar African migratory locusts, Locusta
      migratoria could learn to associate visual cues with the macronutrient content of
      synthetic foods. During a 48-h training period, the insects had ad libitum access
      to two synthetic foods which were identical in all respects except that one
      lacked protein and the other lacked digestible carbohydrate. One food was placed
      at the end of a transparent Perspex cylinder which had been tinted green, and the
      other at the end of a yellow-tinted cylinder which was similar in all other
      respects. To obtain a balanced diet, the insects were thus forced to ingest the
      two macronutrients in visually different environments. Following this training
      period, they were then made selectively deficient in either protein or
      carbohydrate, before being tested for their tendency to enter, and the depth of
      entry into, yellow- or green-tinted cylinders that did not contain food. Locusts
      entered significantly more frequently the colour of cylinder that had previously
      been paired with the deficient nutrient (henceforth termed the 'training
      colour'). This was true irrespective of whether the nutrient was protein or
      carbohydrate, and whether the training colour was green or yellow. There was no
      effect of training on the average depth of entry into the cylinders. However,
      protein-deprived locusts penetrated significantly more deeply than carbohydrate
      deprived locusts into both green and yellow cylinders, irrespective of the
      training colour. A separate experiment demonstrated that naive locusts entered
      more frequently into the yellow than the green side-arm, but there was no
      influence of colour on the depth of entry by naive locusts.Copyright 1997 The
      Association for the Study of Animal BehaviourCopyright 1997The Association for
      the Study of Animal Behaviour.

PMID- 9521799
TI  - Unequal subfamily proportions among honey bee queen and worker brood
AB  - Queens from three colonies of feral honey bees, Apis mellifera were removed and
      placed in separate nucleus colonies. For each colony, eggs and larvae were taken
      from the nucleus and placed in the main hive on each of 3-4 consecutive weeks.
      Workers in the queenless parts selected young larvae to rear as queens. Queen
      pupae, together with the surrounding worker pupae, were removed from each colony
      and analysed at two to three microsatellite loci to determine their paternity. In
      all three colonies, the paternity of larvae chosen by the bees to rear as queens
      was not a random sample of the paternities in the worker brood, with certain
      subfamilies being over-represented in queens. These results support an important
      prediction of kin selection theory: when colonies are queenless, unequal
      relatedness within colonies could lead to the evolution of reproductive
      competition, that is some subfamilies achieving greater reproductive success than
      others. The mechanism by which such dominance is achieved could be through a
      system of kin recognition and nepotism, but we conclude that genetically based
      differential attractiveness of larvae for rearing as queens is more
      likely.Copyright 1997 The Association for the Study of Animal BehaviourCopyright
      1997The Association for the Study of Animal Behaviour.

PMID- 9521800
TI  - How many birds does it take to put a flock to flight?
AB  - Flights from foraging flocks of sanderlings, Calidris alba were observed at
      Redcar, northeast England, in order to investigate how individual decisions to
      fly related to the behaviour of other flock members. Flights of sanderlings
      tended to be either of all birds in the flock on the ground, or of single birds
      or groups representing only a small proportion of the foraging flock. The latter
      accounted for the majority of movement events but after weighting by flock size
      the former accounted for the majority of bird movements. As flock size increased,
      the number of birds that flew without the whole flock taking flight increased.
      Thus, as flock size increased, it took more individual departures before the
      whole flock took flight. When flocks were disturbed by people or dogs, they were
      more cohesive, with more departures being of whole flocks.Copyright 1997 The
      Association for the Study of Animal BehaviourCopyright 1997The Association for
      the Study of Animal Behaviour.

PMID- 9521801
TI  - Self-recognition in Saguinus? A critical essay
AB  - No abstractCopyright 1997 The Association for the Study of Animal
      BehaviourCopyright 1997The Association for the Study of Animal Behaviour.

PMID- 9521802
TI  - Life beyond the mirror: a reply to Anderson & Gallup
AB  - No abstractCopyright 1997 The Association for the Study of Animal
      BehaviourCopyright 1997The Association for the Study of Animal Behaviour.

PMID- 9521803
TI  - Associative learning of visual and vestibular stimuli in Lymnaea.
AB  - A conditioned withdrawal response was characterized in the pond snail Lymnaea
      stagnalis. Using light as the conditioned stimulus and high-speed orbital
      rotation as the unconditioned stimulus, experimental animals were trained with 30
      paired presentations of light and orbital rotation per day for 3 days. After
      training, all experimental animals responded to light with a withdrawal response,
      the conditioned response. Control animals exposed to the same number of
      explicitly unpaired presentations of light and orbital rotation, light alone, or
      no stimulation did not respond to light. Thirty paired presentations per day for
      2 days produced less than optimal acquisition of the conditioned withdrawal
      response. Neither 45 paired presentations per day for 2 days nor 90 paired
      presentations for 1 day resulted in complete acquisition of the conditioned
      withdrawal response. The conditioned withdrawal response observed following 30
      paired presentations per day for 3 to 5 days persisted to Day 10, regardless of
      the number of training days. As a measure of savings, reacquisition of the
      conditioned response after extinction was investigated. After the conditioned
      withdrawal response was extinguished, only 2 to 5 paired presentations of light
      and orbital rotation were required for reacquisition of the conditioned response
      for most animals. This study further establishes Lymnaea as an animal model of
      basic associative learning.

PMID- 9521804
TI  - Structural studies of alpha-N-acetylgalactosaminidase: effect of glycosylation on
      the level of expression, secretion efficiency, and enzyme activity.
AB  - alpha-N-Acetylgalactosaminidase (alphaNAGAL, EC 3.2.1.49) is an exoglycosidase
      specific for the hydrolysis of terminal alpha-linked N-acetylgalactosamine from
      oligosaccharide chains. After cloning of its cDNA, the recombinant alphaNAGAL
      (ralphaNAGAL) was produced in Pichia pastoris, a methylotrophic yeast strain. The
      enzyme was hyperglycosylated by the host cells, resulting in a protein with a
      molecular mass of approximately 50 kDa, which was 7 kDa larger than that of its
      native counterpart. When deglycosylated with endoglycosidase H under
      nondenaturing conditions, ralphaNAGAL remained fully active, suggesting that the
      glycosylation is not required for enzyme activity. Data derived from mass
      spectrometry indicated that all three putative N-glycosylation sites [Asn
      residues at positions 161 (N1), 185 (N2), and 369 (N3)] in the enzyme were
      glycosylated, and a high-mannose structure, which was possibly phosphorylated,
      was attached to the sites N1 and N2. In order to examine the effect of individual
      N-linked oligosaccharide chains on the expression of ralphaNAGAL in P. pastoris,
      we mutated each of the N-glycosylation sites, as well as all three sites in the
      same protein molecule, by substituting the Asn with a Gln residue. The results
      indicate that ralphaNAGAL mutations in any of the three glycosylation sites, N2
      being the most profound, impaired the expression level, altered subcellular
      distribution, and decreased the efficiency of secretion. Our data suggest that
      the N-glycosylation of ralphaNAGAL expressed in P. pastoris may be important in
      protein folding and resistance to protease degradation during protein synthesis,
      although it is apparently not required for enzyme activity.

PMID- 9521805
TI  - Expression of functional aromatic hydrocarbon receptor and aromatic hydrocarbon
      nuclear translocator proteins in murine bone marrow stromal cells.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) acting through the aromatic
      hydrocarbon receptor (AhR) and its dimerization partner, the AhR nuclear
      translocator protein (arnt), elicits numerous toxicological effects including
      immunosuppression and thymic atrophy. Previous work has shown that TCDD alters
      bone marrow prothymocyte populations. These effects could be mediated at the
      lymphocyte level directly and/or through effects on bone marrow stromal cells, a
      population important in the support of lymphopoiesis. The purpose of this study
      was to characterize AhR and arnt expression in three murine bone marrow stromal
      cell lines (S17, M2-10B4, and BMS2) and in primary stromal cell cultures.
      Immunoblot analysis detected AhR protein in M2-10B4 and BMS2 cells. AhR protein
      was also detected in the primary cultures. Arnt protein could be detected in all
      cell cultures. Electrophoretic mobility shift assays detected TCDD-dependent
      dioxin-responsive element (DRE) binding in all three cell lines. DNA binding was
      sequence-specific and dependent on AhR, as demonstrated by the addition of
      unlabeled DRE DNA or of anti-AhR antibody. Results obtained with the primary
      cultures paralleled those seen with the stromal cell lines. The ED50 for
      induction of TCDD-dependent DRE binding in M2-10B4 cells was 0.21 nM. TCDD
      treatment did not induce stromal P4501A1 mRNA expression but did increase P4501B1
      mRNA levels in all three cell lines and in the primary cultures. These results
      indicate that murine bone marrow stromal cells express AhR and arnt proteins.
      Furthermore, these proteins are functional in terms of their DRE-binding ability
      and potential to regulate mRNA levels in a gene-specific fashion.

PMID- 9521806
TI  - Differential effects of unilateral lidocaine infusion into the globus pallidus on
      consolidation and performance of inhibitory avoidance.
AB  - The striatum is involved in memory consolidation; also involved in this process
      is one of its two major efferent targets, namely, the substantia nigra. It is not
      clear, however, if the other target, the globus pallidus, participates in storage
      and/or performance of learned information. To examine this problem, male Wistar
      rats were trained in an inhibitory avoidance task and tested for retention 24 h
      afterward. Independent groups were infused, unilaterally, with 2% lidocaine in
      the pallidus either 2 min after training or 2 min before testing. No disturbances
      of memory were detected with posttraining infusion, but a significant deficit in
      retention was observed as a consequence of pretest infusion. Infusion of isotonic
      saline into the globus pallidus, or of lidocaine before testing into the parietal
      cortex, after training into the ventral thalamic nucleus, and both before
      training and testing into this thalamic nucleus were without effect. Taken
      together, the data indicate that unilateral inactivation of the GP interferes
      with retrieval of information derived from inhibitory avoidance training, but not
      with the early stages of memory consolidation of this task, and other work
      indicates that the pallidus may be involved in a late phase of this process.

PMID- 9521807
TI  - Electrochemical oxidation of N-acyldopamines and regioselective reactions of
      their quinones with N-acetylcysteine and thiourea.
AB  - The metabolism of catechols often involves their oxidation to quinones and
      subsequent nucleophilic addition reactions with sulfur-containing compounds.
      Adducts formed during these reactions may play important roles in many biological
      systems. We have studied the electrochemical oxidation of N-acetyldopamine (NADA)
      and N-beta-alanyldopamine (NBAD) in the presence of two sulfur-centered
      nucleophiles, N-acetylcysteine (NACySH) and thiourea (TU), and have characterized
      the adducts and reaction pathways. NADA and NBAD react similarly, but their
      adducts with NACySH and TU were formed regioselectively. NACySH yields mainly 5
      adducts and TU only 6-adducts. The NACySH adducts are oxidized more easily than
      the parent N-acyldopamine, and their oxidations are chemically reversible.
      However, the TU adducts are more difficult to oxidize, and their oxidation
      products undergo further chemical reactions. An intramolecular base catalysis
      mechanism for adduct formation with NACySH is proposed, which facilitates removal
      of the proton from the sulfhydryl group of NACySH and directs formation of the 5
      adduct via a 1,6-Michael addition reaction. The absence of a proton on the
      thioureylene sulfur atom leads to formation of the 6-thioureylene adduct via a
      1,4-Michael addition reaction of TU. This mechanism is consistent with the
      formation of other sulfur-centered adducts of catechols previously reported in
      the literature.

PMID- 9521808
TI  - Fimbria-fornix vs selective hippocampal lesions in rats: effects on locomotor
      activity and spatial learning and memory.
AB  - The behavioral effects of interrupting the axons that pass in the fimbria and
      dorsal fornix were compared with the effects of selective removal of the cells
      that comprise the hippocampus with ibotenic acid. Starting 4.5 months after
      surgery, lesioned and control rats were (i) trained in both the Morris water maze
      and the eight-arm radial maze using protocols that placed an emphasis on either
      working memory (WM) or reference memory (RM) and (ii) tested for locomotor
      activity in the home cage. In comparison to sham-operated rats, the rats from
      both lesion groups were impaired in most learning/memory tasks, but there were
      some interesting differences between the two lesioned groups. When compared to
      rats with fimbria-fornix lesions (FIFX rats), hippocampal rats (HIPP rats) were
      slower in learning to swim to a visible platform and showed a greater impairment
      than FIFX rats in the radial-maze task when the testing procedure required the
      utilization of RM and WM in a more demanding WM task. In the test of locomotor
      activity, FIFX and control rats did not differ, but HIPP rats were more active
      than the rats in both other groups. The pattern of results obtained after a 4.5
      month recovery period support the following general conclusions. (1) While there
      are some similarities in the effects on behavior of interrupting the axons in the
      fimbria-fornix compared to removing the hippocampus, there are some important
      differences. (2) From the findings that are available, a possible explanation to
      account for the difference between FIFX and HIPP rats is that the 4.5-month
      survival time permitted some recovery in the group of rats with FIFX lesions. (3)
      While it is well known that the Morris water maze and the radial-arm maze tasks
      provide useful measures of spatial learning and memory processes, our results
      suggest that the information provided by the two spatial learning tasks may
      differ in important respects.

PMID- 9521809
TI  - Molecular cloning and characterization of a novel nuclear protein kinase in mice.
AB  - We cloned cDNAs which encode a mouse liver nuclear protein with an apparent
      molecular mass of 51 kDa, using sequences derived from a purified protein as the
      basis for designing specific primers. The deduced amino acid sequences revealed
      that the 51-kDa protein contains characteristic subdomain structures of a protein
      kinase. The bacterially expressed recombinant 51-kDa protein catalyzed
      phosphorylation of general substrates such as casein and was autophosphorylated
      at serine residue(s). This 51-kDa protein kinase, designated 51PK, is 40%
      identical to the 34-kDa protein kinase encoded by the vaccinia virus B1 gene and
      25% identical to the casein kinase I isoforms, including yeast HRR25. The 51PK
      mRNA was expressed as two splice variants and the 51PK protein was exclusively
      localized in nuclei. Northern hybridization showed that 51PK mRNA was expressed
      in various tissues, with highest levels in testis, spleen, lung, and liver. These
      results, therefore, indicate that 51PK is a nuclear serine/threonine kinase and a
      novel distinct member of the protein kinase superfamily.

PMID- 9521810
TI  - The Leu-3 residue of Serratia marcescens metalloprotease inhibitor is important
      in inhibitory activity and binding with Serratia marcescens metalloprotease.
AB  - Serratia marcescens metalloprotease inhibitor (SmaPI) is a proteinase inhibitor
      toward Serratia marcescens metalloprotease (SMP). In sequential deletion analysis
      of the N-terminal region of the SmaPI, SmaPIs starting at Ser-2 and Leu-3
      residues, respectively, had nearly a full inhibitory activity toward SMP.
      However, SmaPI starting at Ala-4 residue showed severely decreased inhibitory
      activity. Furthermore, kinetic analysis demonstrated that SmaPI starting at the
      Ala-4 residue had an inhibition constant for SMP approximately fourfold higher
      than that of wild-type SmaPI. The interactions of Leu-3 with SMP contribute 0.73
      kcal mol-1 to the overall stability of the SMP-SmaPI complex (8.44 kcal mol-1).
      To elucidate the detailed role of the Leu-3 residue in inhibitory activity of
      SmaPI, several site-directed mutations were introduced. The inhibitory activities
      of Leu-3 mutants in which the Leu-3 has been converted to Ala, Asp, Gly, Ile,
      Lys, Phe, or Pro were correlated with the hydrophobicities of substituted amino
      acids. About 0.3 kcal mol-1 is attributable to the side chain of the Leu-3
      residue in the binding with SMP. From these results, it is suggested that (i) in
      contrast with the Erwinia chrysanthemi inhibitor, Gly-1 and Ser-2 of SmaPI are
      not critical and (ii) the hydrophobicity of Leu-3 may be important in its
      inhibitory activity and binding with SMP.

PMID- 9521811
TI  - Alkaline lipase from brain: is it the same enzyme as pancreatic lipase from
      pancreas?
AB  - A new alkaline lipase was detected in rat brain and its properties were compared
      with those of the well-characterized pancreatic lipase and pancreatic lipase
      related protein 2. The activity of the alkaline lipase was determined using
      trioleoylglycerol emulsion at pH 8.0. Subcellular fractions were prepared from
      brain homogenates by differential centrifugation. Lipase activities of the
      cytosolic fraction (the supernatant obtained by differential centrifugation of
      100,000g) were stimulated by addition of colipase and bile salts and inhibited by
      addition of an antibody against rat pancreatic lipase. The partially purified
      enzyme had an isoelectric point of pH 6.8, which was identical to that found for
      rat pancreatic lipase. The enzyme had interfacial activation and dependence on
      colipase in the presence of bile salts. The enzyme had no measurable
      phospholipase A activity. The band produced by the enzyme on SDS-polyacrylamide
      gel electrophoresis was identical to that of the rat pancreatic lipase when
      detected by immunoblotting analysis using an antibody against pancreatic lipase.
      These results show that pancreatic lipase such as alkaline lipase is in rat
      brain.

PMID- 9521812
TI  - Histological and behavioral protection by (-)-nicotine against quinolinic acid
      induced neurodegeneration in the hippocampus.
AB  - Injections of quinolinic acid (60, 180, and 600 nmol) in the dorsal hippocampus
      induced significant neurotoxicity that was evident 1 day after the injection. By
      day 3, pyramidal as well as granular cells were affected even at the lowest dose
      of quinolinic acid, an effect that persisted up to 20 days. Consistent with the
      histological findings, animals with bilateral injections in the dorsal
      hippocampus were cognitively impaired during acquisition and retention of spatial
      information in the water maze. A subacute treatment with (-)-nicotine (62
      micromol/kg/day) delivered by subcutaneous minipumps prevented the histological
      and cognitive deficits induced by the bilateral quinolinic acid (60 nmol)
      injections. These data indicate that quinolinic acid can induce degeneration of
      both pyramidal as well as granule cells in the hippocampus, leading to cognitive
      impairments in the rat, and that activation of neuronal nicotinic acetylcholine
      receptors can prevent the neurodegenerative process induced by quinolinic acid.

PMID- 9521813
TI  - Hemin-enhanced resistance of human leukemia cells to oxidative killing: antisense
      determination of ferritin involvement.
AB  - Human HL-60 cells exhibited a strong hyperresistance to the lethal effects of
      photodynamic activity (singlet oxygen) or glucose oxidase activity (hydrogen
      peroxide) 16-20 h after being exposed to hemin (ferriprotoporphyrin IX).
      Hyperresistance was accompanied by the overproduction of immunodetectable
      ferritin, predominantly the heavy (H) subunit, which exhibits ferroxidase
      activity. Cells that had been enriched in apoferritin via pinocytotic uptake
      showed similar hyperresistance to both types of oxidative challenge. On the other
      hand, preincubating cells with hemin in the presence of a phosphorothioate-linked
      antisense oligodeoxynucleotide against H-ferritin mRNA resulted in a strong
      diminution in both hyperresistance and H-ferritin induction. No effects were seen
      when a scrambled order oligodeoxynucleotide of the same base composition was
      used, confirming that the antisense oligomer had specifically inhibited H
      ferritin translation. These results indicate that induced ferritin played a
      crucial role in the observed cytological responses. Enhanced oxidant resistance
      is attributed to the ability of this ferritin to rapidly sequester and
      incapacitate redox-active iron.

PMID- 9521815
TI  - Posttraining administration of substance P and its N-terminal fragment block the
      amnestic effects of diazepam.
AB  - This study examined the effects of posttraining administration of substance P
      (SP) and of certain N- or C-terminal SP-fragments on retention performance of
      rats treated with diazepam (DZP). Twenty minutes before the training on an
      inhibitory avoidance task rats were given intraperitoneal injections of either
      DZP (2 mg/kg) or vehicle. Immediately after they were injected with SP (50
      micrograms/kg), SPN 1-7 (167 micrograms/kg), SPC 6-11 (134 micrograms/kg), or
      vehicle. The posttrial administration of SP and SPN, but not SPC, facilitated
      avoidance behavior. Animals that received DZP before training and vehicle after
      the conditioning trial showed impaired retention. In contrast, in animals
      injected with SP and SPN after the training trial, DZP did not affect retention.
      These findings suggest that the amnestic effects of DZP can be blocked by the
      administration of SP and that the amino acid sequence responsible for this effect
      may be encoded by its N-terminal part.

PMID- 9521814
TI  - Protein tyrosine kinase inhibitors block tumor necrosis factor-induced activation
      of nuclear factor-kappaB, degradation of IkappaBalpha, nuclear translocation of
      p65, and subsequent gene expression.
AB  - Several inflammatory effects of tumor necrosis factor (TNF) are known to be
      mediated through activation of a nuclear transcription factor NF-kappaB, but how
      TNF activates NF-kappaB is incompletely understood. In the present report, we
      examined the role of protein tyrosine kinases (PTK) in TNF-mediated NF-kappaB
      activation by using genistein and erbstatin, two potent inhibitors of PTK. The
      treatment of human myeloid U-937 cells with either inhibitor completely
      suppressed the TNF-induced NF-kappaB activation in a dose- and time-dependent
      manner. Suppression correlated with PTK activity, since among the structural
      analogues of genistein, only an active inhibitor of PTK, quercetin blocked TNF
      induced NF-kappaB activation and not daidzein, an inactive inhibitor. Inhibition
      of NF-kappaB activation was not limited to myeloid cells, as it was observed with
      T cells and epithelial cells. Both the PTK inhibitors blocked the degradation of
      IkappaBalpha, the inhibitory subunit of NF-kappaB, and the consequent
      translocation of the p65 subunit without any significant effect on p50 or on c
      Rel. The PTK inhibitors did not interfere with NF-kappaB binding to DNA. The NF
      kappaB-dependent CAT reporter gene expression in transient transfection assays
      was also suppressed by the PTK inhibitors. Both PTK inhibitors abolished TNF
      induced activation of N-terminal c-Jun kinase and mitogen-activated protein
      kinase kinase. Overall, our results suggest that a genistein- and erbstatin
      sensitive PTK is involved in the pathway leading to NF-kappaB activation and gene
      expression by TNF and thus could be used as a target for development of
      antiinflammatory drugs.

PMID- 9521816
TI  - Temporal determinants of olfactory long-term retention in honeybee classical
      conditioning: nonmonotonous effects of the training trial interval.
AB  - The question of which acquisition parameters govern long-term retention is
      important to an understanding of memory function. We investigate the effects of
      the time interval between learning trials on mediate (1 day)- and long-term (4
      days) retention. In classical conditioning of the proboscis extension reflex, we
      train honeybees to associate an odorant with a sucrose reward using intertrial
      intervals of either 30 s, 1 min, 3 min, or 20 min. Intervals of 20 and 1 min
      result in stable retention but 3-min and 30-s intervals result in reduced
      retention after 4 days compared to that seen after 1 day. Thus, stability of long
      term retention depends nonmonotonously on the intertrial interval. Reduced
      retention with 3-min intervals might be caused by a disruption of memory
      consolidation which is known to be especially sensitive to interference 3 min
      after a conditioning trial. Habituation and backward inhibitory learning are
      discussed as explanations for reduced retention with 30-s intervals.

PMID- 9521817
TI  - Mutational analysis of the four alpha-helix bundle iron-loading channel of rat
      liver ferritin.
AB  - We previously reported that the heavy chain of ferritin was required for loading
      it with iron using ceruloplasmin as a ferroxidase [J.-H. Guo, M. Abedi, and S. D.
      Aust (1996) Arch. Biochem. Biophys. 335, 197-204]. Site-directed mutagenesis,
      K58E and G61H, on recombinant rat liver L chain ferritin (rL-Ft) was performed to
      construct a proposed iron-loading channel in the alpha-helix bundle similar to
      rat liver H chain ferritin (rH-Ft). Conversely, the channel in rH-Ft was closed
      by mutations E62K and H65G to form a K62 to E107 salt bridge, which is believed
      to exist in the L chain. Both variants were expressed in insect cells and were
      soluble and able to form multi-subunit homopolymers. The rH-Ft mutant homopolymer
      could not be loaded, whereas the rL-Ft mutant homopolymer could be loaded with
      iron by ceruloplasmin. However, we found that the initial rate of iron loading
      into the rL-Ft mutant homopolymer by ceruloplasmin was less than that into the rH
      Ft homopolymer. When 500 atoms of iron per ferritin were used for loading, 98%
      was loaded into the rH-Ft homopolymer by ceruloplasmin in 15 min, but only 30%
      was loaded into the rL-Ft mutant homopolymer in the same time. Moreover, the
      ferroxidase activity of ceruloplasmin was enhanced in the presence of the rH-Ft
      and the rH-Ft mutant homopolymers, but not in the presence of the rL-Ft or the rL
      Ft mutant homopolymers. These observations suggested that the four alpha-helix
      bundle channel of ferritin is required for iron loading, but an additional
      factor, i.e. , a site which stimulate the ferroxidase activity of ceruloplasmin,
      is also essential.

PMID- 9521818
TI  - Characterization of the secondary structure and membrane interaction of the
      putative membrane anchor domains of prostaglandin I2 synthase and cytochrome P450
      2C1.
AB  - Prostaglandin I2 synthase (PGIS) produces prostaglandin I2 (PGI2) which has
      opposite actions on platelet aggregatory and vasoconstrictive properties compared
      to thromboxane A2 (TXA2) produced from the same substrate by another P450 enzyme,
      thromboxane A2 synthase (TXAS). PGIS and TXAS have only 16% amino acid sequence
      identity. Hydropathy analysis suggests that the putative NH2-terminal membrane
      anchor domain of PGIS is similar to many other membrane-bound microsomal P450s,
      which are believed to be anchored by a single transmembrane segment, and thus
      different from the TXAS anchor, which appears to have two transmembrane segments.
      To characterize the membrane anchor function of the PGIS NH2-terminal region, we
      have used the peptidoliposome reconstitution assay to identify the membrane
      anchor segment in the PGIS NH2-terminal domain and compared it with the anchor
      segment of P450 2C1. Four peptides, mimicking putative NH2-terminal membrane
      anchor segments of PGIS and P450 2C1, containing residues 1-28 (PGIS-LP1 and P450
      2C1-LP1) or residues 25-54 (PGIS-LP2 and P450 2C1-LP2), were synthesized and
      their ability to insert in a lipid bilayer was evaluated. The results indicated
      that both LP1 peptides of PGIS and P450 2C1 became bound to the lipid bilayer,
      whereas both LP2 peptides did not bind the lipid. The two LP1 peptides were
      further characterized as to their conformation using CD spectroscopy. Helical
      structure induced in these peptides by addition of trifluoroethanol,
      dodecylphosphocholine, or incorporation into liposomes indicated that these
      segments tend to adopt a helical structure in a hydrophobic environment and thus
      could function as membrane anchor segments. These results support the hypothesis
      that PGIS and TXAS interact with the endoplasmic reticulum membrane in different
      ways, in which the NH2-terminal anchor domain of PGIS, as with P450 2C1, appears
      to have a single transmembrane segment.

PMID- 9521819
TI  - Further support for nitric oxide-dependent memory processing in the day-old
      chick.
AB  - There is considerable evidence that nitric oxide activity is essential for memory
      formation, particularly from studies using inhibitors of nitric oxide synthase.
      The particular stage of memory formation requiring nitric oxide activity has not,
      however, been systematically investigated. In the current experiments, day-old
      black Australorp-white Leghorn chicks were trained on a passive avoidance task.
      Intracranial injections of the nitric oxide synthase inhibitor, l-NG
      nitroarginine methylester (0.5 mM), were found to inhibit memory formation
      shortly after training, when injected pre- or posttraining. This effect was
      replicated with a second inhibitor, l-NG-nitroarginine (1 mM), and counteracted
      by the NO donor, sodium nitroprusside (150 microM). These findings provide
      covergent evidence that nitric oxide activity plays a critical role in the
      consolidation of memory in the day-old chick.

PMID- 9521820
TI  - Degradation of yeast cytochromes c dependent and independent on its physiological
      partners.
AB  - Altered iso-1- and iso-2-cytochromes c, with certain amino acid replacements,
      occur at diminished levels due to degradation in the yeast Saccharomyces
      cerevisiae. A subclass of the labile isocytochromes c are significantly protected
      from degradation by the presence of cytochromes a.a3 and c1, the physiological
      partners of cytochrome c. We have investigated the degradation that is dependent
      on physiological partners by examining the levels of iso-1-cytochrome c having
      all or most amino acid replacements at positions 6, 41, 52, and 78, in both rho+
      strains and rho- strains, which lacks cytochrome a.a3. In addition, we have
      examined some of these replacements in strains also having the N52I replacement,
      which suppresses a variety of abnormal iso-1-cytochromes c, including those whose
      degradation is either dependent or independent on the physiological partners.
      Although some degree of preferential rho--dependent reductions was observed for
      iso-1-cytochromes c having replacements at each of the 6, 41, 52, and 78 sites,
      prominent effects of rho+/rho- ratios of approximately 100/0 to 30/0 were
      observed for iso-1-cytochromes c having replacements mainly at the 41, 52, and 78
      sites, but not the G6 site. We suggest that prominent degradation dependent on
      physiological partners may be restricted to certain regions of the cytochrome c
      molecule. Furthermore, we suggest that the region of the largest confirmational
      difference between oxidized and reduced cytochrome c appears to be particularly
      protected by interactions with its physiological partners.

PMID- 9521821
TI  - Studies on the protein tyrosine phosphatase activity of tartrate-resistant acid
      phosphatase.
AB  - Tartrate-resistant acid phosphatase (TRAP) is an enzyme with unknown biological
      function. In human tissues, its expression is restricted to bone-resorbing
      osteoclasts and activated macrophages. Osteoclasts secrete TRAP to the
      circulation during bone resorption. Reduction of the enzyme's binuclear iron
      center is important in regulating its activity. The purple form of the enzyme is
      inactive and contains two ferric ions. Mild reduction activates it to a pink form
      containing one ferric and one ferrous ion. Instead, strong reduction removes the
      iron content, resulting in a colorless, inactive enzyme. We describe spontaneous
      activation of the purple form to the pink form upon incubation at +37 degrees C.
      Further incubation results in slow inactivation of the enzyme and color change to
      yellowish. The enzyme purified from osteoclasts is a mixture of the purple and
      pink forms, but the enzyme purified from serum represents the yellowish form. We
      suggest that the newly synthesized enzyme is purple and reduced in the cell to
      the functionally active pink form. After fulfilling its biological function in
      the cell, the enzyme is further reduced to the yellowish form and secreted into
      the circulation. In the serum, further reduction would dissociate the iron
      content. The enzymes from osteoclasts and macrophages had similar catalytic
      properties, both being active as a protein tyrosine phosphatase (PTPase). The
      acid phosphatase (AcP) and PTPase activities were similar, and the preferred AcP
      substrate, pNPP, was processed in the same active site as phosphotyrosine. Our
      results suggest that redox-regulated PTPase activity may be a major function of
      TRAP in vivo.

PMID- 9521822
TI  - Active-site disruption in native Limulus hemocyanin and its subunits by disulfide
      bond reductants: a chemical probe for the study of structure-function
      relationships in the hemocyanins.
AB  - The crystal structure analysis of Subunit II of Limulus hemocyanin has shown that
      its polypeptide chain is folded into three distinct structural domains. The
      oxygen-binding, dinuclear copper center is located deep in the core of Domain 2.
      Two disulfide bonds are located in a bridging domain, Domain 3. These disulfide
      bonds are remote from the oxygen-binding site, but are positioned so that they
      could affect its stability. When the disulfide bonds are broken by dithiothreitol
      or other disulfide-bond reductants, the 340-nm absorption band, associated with
      oxygen binding, is lost. Disulfide-bond reductants also cause the loss of the
      oxygen-binding capacity of all seven of the other subunits of Limulus hemocyanin.
      Thus, disulfide bonding is a general feature of the Limulus hemocyanin subunits
      that is important to the maintenance of the physiologically effective geometry of
      the oxygen-binding site. The rate of loss of oxygen-binding capacity, however, is
      highly dependent on subunit type, aggregation state, and protein conformation.
      Evidence that protein conformation markedly affects the rate of disruption of the
      oxygen-binding site comes from the finding that the addition of dithiothreitol to
      fully oxygenated samples results in a slow initial loss of oxygen-binding
      capacity followed by an appreciably faster reaction rate. In contrast, in the
      deoxygenated conformation, the reaction rate is monophasic and never attains the
      faster rates observed for oxygenated samples. When the disulfide bonds are broken
      and oxygen-binding capacity is lost, there is subunit-specific variability in the
      extent of polypeptide-chain unfolding, subunit aggregation, and loss of active
      site copper ions. When the disulfide-bond reductant is removed by dialysis so
      that disulfide bonds can re-form, there is also subunit-specific variability in
      the extent of restoration of oxygen-binding capacity. Complete restoration of
      structure and function as the disulfide bonds re-form occurs only for the 48
      subunit native molecule, whose architecture is stabilized by bound Ca2+ and
      extensive intersubunit contacts. We have found a similar loss of oxygen-binding
      capacity upon breaking disulfide bonds in a number of other arthropod and mollusc
      hemocyanins, suggesting that the active site of Limulus hemocyanin is not unique
      in its dependence upon intact disulfides. The results presented in this paper
      suggest that disulfide-bond reduction may provide a simple, but powerful,
      chemical tool with which to probe internal and environmental factors that govern
      physiologically important structure-function relationships in the hemocyanins.

PMID- 9521823
TI  - 3-Hydroxy-3-methyl-glutaryl-CoA reductase in Trypanosoma (Schizotrypanum) cruzi:
      subcellular localization and kinetic properties.
AB  - The subcellular localization of 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA)
      reductase, which catalyzes the first committed step of the mevalonate pathway,
      was investigated in Trypanosoma cruzi epimastigotes using well-established cell
      fractionation procedures. It was found that ca. 80% of the activity of the enzyme
      was associated with the glycosomes, microbody-like organelles unique to
      kinetoplastid protozoa which contain most of the enzymes of the glycolytic
      pathway, while the rest of the activity was found in the soluble (cytoplasmatic)
      fraction, with almost no activity associated with microsomes. The glycosome
      associated enzyme is not membrane-bound as it was recovered quantitatively in the
      aqueous phase of the biphasic system formed by Triton X-114 at 30 degrees C.
      Studies with digitonin-permeabilized intact epimastigotes demonstrated the
      presence of two pools of soluble HMG-CoA reductase in these cells, associated to
      the cytoplasmic and glycosomal compartments. Steady-state kinetic studies of the
      glycosome-associated enzyme indicated classical Michaelis-Menten behavior with
      Km,app (HMG-CoA) 28 +/- 3 microM, Km,app (NADPH) 37 +/- 4 microM, and Vm,app 3.9
      +/- 0.2 nmol/min mg protein; the transition-state analog lovastatin behaved as a
      competitive inhibitor with respect to HMG-CoA with Kis 23 nM and a noncompetitive
      inhibitor toward NADPH with Kii 29 nM. The results are in complete agreement with
      recent gene cloning and expression studies which showed that T. cruzi HMG-CoA
      reductase lacks the NH2-terminal membrane-spanning sequence. This is the first
      demonstration of a soluble eukaryotic HMG-CoA reductase and also the first report
      on the presence of an enzyme of the isoprenoid biosynthesis pathway in
      glycosomes.

PMID- 9521824
TI  - Nitration of veratryl alcohol by lignin peroxidase and tetranitromethane.
AB  - Lignin peroxidase (LiP), from Phanerochaete chrysosporium, in the presence of
      H2O2 and tetranitromethane (TNM), oxidizes veratryl (3,4-dimethoxybenzyl) alcohol
      (VA) (I) to veratraldehyde (IV), 4,5-dimethoxy-2-nitrobenzyl alcohol (V), and 3,4
      dimethoxy-nitrobenzene (VI). The formation of these products is explained by a
      mechanism involving the one-electron oxidation of VA by LiP to produce the
      corresponding cation radical, which loses a proton to generate the benzylic
      radical. The latter reduces TNM to generate the trinitromethane anion (VIII) and
      the nitrogen dioxide radical (.NO2). .NO2 couples with the VA cation radical, and
      the subsequent loss of a proton leads to V. Alternatively, the attack of .NO2 at
      C-1 of the VA cation radical, followed by aromatization and loss of formaldehyde
      (VII), yields VI. Isotopic labeling experiments confirm that V is generated by
      the reaction of .NO2 with the VA cation radical, rather than with the benzylic
      radical. The nitration of two other LiP substrates, 1,4-dimethoxybenzene (II) and
      tyrosine (III), also was examined. Product analysis of reactions conducted in the
      presence of H2O2 with these substrates indicated less nitrated product was formed
      from 1,4-dimethoxybenzene and no nitrated product was formed from tyrosine.
      However, significant amounts of nitrated products were formed from 1,4
      dimethoxybenzene and tyrosine when glucose and glucose oxidase were used as an
      H2O2 source. These results suggest that a reductant, either the veratryl alcohol
      benzylic radical or superoxide, is required in the reaction to reduce TNM to
      generate .NO2. These results provide further evidence for the formation of the VA
      cation radical and the first chemical evidence for the formation of the VA
      benzylic radical in LiP-catalyzed reactions.

PMID- 9521825
TI  - Roles and microenvironments of tryptophanyl residues of spinach
      phosphoribulokinase.
AB  - Phosphoribulokinase is one of several Calvin cycle enzymes that are light
      regulated via the ferredoxin-thioredoxin system (R. A. Wolosiuk and B. B.
      Buchanan, 1978, Arch. Biochem. Biophys. 189, 97-101). Substitution of the only
      two Trp residues of the enzyme was prompted by the following goals: to identify
      each tryptophanyl residue with respect to prior classifications as exposed and
      buried (C. A. Ghiron et al., 1988, Arch. Biochem. Biophys. 260, 267-272); to
      explore the possible active-site location and function of conserved Trp155, as
      suggested by sequence proximity to catalytic Asp160 (H. A. Charlier et al., 1994,
      Biochemistry 33, 9343-9350); and to determine if fluorescence of a Trp residue
      can serve as a gauge of conformational differences between the reduced (active)
      and the oxidized (inactive) forms of the enzyme. Emission spectra and acrylamide
      quenching data demonstrate that Trp155 is solvent exposed, while Trp241 is
      buried. Kinetic parameters of the W241F mutant are not significantly altered
      relative to those of wild-type enzyme, thereby discounting any requirement for
      Trp at position 241. While substitution of Trp155 with Phe or Ala has little
      impact on Vmax, the Km for Ru5P and ATP are increased substantially; the
      diminished affinity for ATP is particularly pronounced in the case of the Ala
      substitution. In further support of an active-site location of Trp155, its
      fluorescence emission is subject to quenching by nucleotides. Fluorescence
      quenching of reduced W241F by ATP gives a dissociation constant (Kd) of 37
      microM, virtually identical with its Km of 46 microM, and provides for the first
      time a direct measurement of the interaction of the kinase with product ADP (Kd
      of 1.3 mM). Fluorescence quenching of oxidized W241F by ATP reveals a Kd of 28
      mM; however, this weakened binding does not reflect an altered microenvironment
      of Trp155, as its steady-state emission and fluorescence lifetimes are unaffected
      by the oxidation state.

PMID- 9521827
TI  - Overexpression, single-step purification, and site-directed mutagenetic analysis
      of casbene synthase.
AB  - Casbene synthase is a diterpene cyclase isolated from castor bean (Ricinus
      communis L), which catalyzes the cyclization of geranylgeranyl diphosphate to
      form the phytoalexin casbene. We here report the overexpression of casbene
      synthase in Escherichia coli in soluble form using a thioredoxin fusion system.
      The amplified DNA by PCR carried on pCS7 was inserted into the expression vector
      pET32b(+) to form pCAS.2. The resulting transformants of pCAS. 2/BL21(DE3)
      produced a thioredoxin casbene synthase fusion protein (20-30% of total soluble
      protein) when induced with isopropyl beta-d-thiogalactopyranoside at 20 degrees
      C. Recombinant casbene synthase was purified to homogeneity in a single step with
      a His-binding metal-affinity column. Casbene synthase has a conserved aspartate
      rich region [amino acids 355-359 (DDTID)], one cysteine, and three histidines
      with several prenyl transferases and terpene cyclases. Seven mutants were
      constructed by site-directed mutagenesis. The importance of Asp 355 and Asp 356
      for catalysis was established by an increase in Km as well as a reduction in kcat
      in the corresponding glutamate mutants. These results indicate that the first and
      the second aspartate are involved in catalysis, while the third aspartate and the
      conserved cysteine and histidine residues selected for mutagenesis appear not to
      be involved in catalysis.

PMID- 9521826
TI  - The choline kinase inhibitor hemicholinium-3 can inhibit mitogen-induced DNA
      synthesis independent of its effect on phosphocholine formation.
AB  - In NIH 3T3 cells, phosphocholine (PCho) stimulates mitogenesis in synergism with
      insulin, ATP, and sphingosine-1-phosphate (S1P) via an extracellular target.
      Intracellular PCho also has been suggested to mediate the mitogenic effects of
      fibroblast growth factor (FGF) and several other growth factors based, in part,
      on the observed inhibition of growth factor-induced mitogenesis by the choline
      kinase inhibitor hemicholinium-3 (HC-3). Here we examined the specificity of HC-3
      effects on mitogenesis in serum-starved NIH 3T3 and Swiss 3T3 cells. In both cell
      lines, FGF greatly enhanced DNA synthesis in a medium containing 28 microM
      choline, and it also stimulated the formation of -14C-PCho from both 50 microM
      and 5 mM [14C]choline. HC-3 (2 mM) inhibited basal or FGF-induced formation of
      [14C]PCho and [14C]phosphatidylcholine as well as the uptake of -14C-choline only
      at the 50 microM, but not the 5 mM, concentration of [14C]choline. In addition,
      HC-3 (1 mM) from three different sources (95-99.9% purity) inhibited FGF
      stimulated DNA synthesis by 53-58% which was not reversed by 5 mM choline. The
      choline analogue dimethylethanolamine (1 mM) also inhibited FGF-stimulated
      formation of [14C]PCho from 50 microM -14C-choline, but it had no effect on FGF
      induced DNA synthesis. Of the other growth regulators examined, synergistic
      stimulation of DNA synthesis by extracellular PCho and S1P or PCho and ATP via
      choline kinase-independent mechanisms was inhibited by 2 mM HC-3. However, HC-3
      failed to inhibit the synergistic mitogenic effects of PCho and insulin or S1P
      and insulin. The results suggest that FGF-induced mitogenesis does not require
      PCho formation and that HC-3 can inhibit DNA synthesis independent of its
      inhibitory effects on choline metabolism.

PMID- 9521828
TI  - Levels of cyclooxygenase-1 and -2 mRNA expression at various stages of acute
      gastric injury induced by ischemia-reperfusion in rats.
AB  - Recently, the state of cyclooxygenase (COX) mRNA expression has been reported in
      an acetic acid-induced chronic gastric ulcer model of mice. However, the time
      course of COX expression during the developmental stage and the subsequent repair
      process of acute gastric injury is not well understood at present. In this study,
      we quantitatively investigated the time course of the level of COX-2 and -1 mRNA
      expression from the developmental stage through the healing stage in ischemia
      reperfusion (I-R)-induced acute gastric damage. COX-2 mRNA was expressed at low
      or undetectable levels in the normal gastric tissues of control rats. The COX-2
      expression between 6 and 48 h following I-R was higher than that of the control
      gastric tissues; the histological findings were erosion during 1-36 h and
      transitional appearance from erosion to ulcer at 48 h. The maximum expression of
      COX-2 mRNA was recorded at 24 h (approximately 200-fold elevation). The COX-2
      message was very low or undetectable at 72 h (ulcer stage) and at 96 and 120 h
      (healing stage of ulcer) after I-R. The level of COX-1 mRNA remained stable
      through all stages of acute gastric damage. These results are potentially useful
      for understanding the role of COX and evaluating the effects of drugs on
      expression of COX at various stages of acute gastric injury.

PMID- 9521829
TI  - Experiences of remembering, knowing, and guessing.
AB  - This article presents and discusses transcripts of some 270 explanations subjects
      provided subsequently for recognition memory decisions that had been associated
      with remember, know, or guess responses at the time the recognition decisions
      were made. Only transcripts for remember responses included reports of
      recollective experiences, which seemed mostly to reflect either effortful
      elaborative encoding or involuntary reminding at study, especially in relation to
      the self. Transcripts for know responses included claims of just knowing, and of
      feelings of familiarity. These transcripts indicated that subjects were often
      quite confident of the accuracy of their decisions, compared with those for guess
      responses. Transcripts for decisions associated with guess responses also
      expressed feelings of familiarity but additionally revealed various strategies
      and inferences that did not directly reflect memory for studied items. The
      article concludes with a historical and theoretical overview of some
      interpretations of the states of awareness measured by these responses.

PMID- 9521830
TI  - Apparent amnesia on experimental memory tests in dissociative identity disorder:
      an exploratory study.
AB  - Dissociative identity disorder (DID; called multiple personality disorder in
      DSMIII-R) is a psychiatric condition in which two or more identity states
      recurrently take control of the person's behavior. A characteristic feature of
      DID is the occurrence of apparently severe amnestic symptoms. This paper is
      concerned with experimental research of memory function in DID and focuses on
      between-identity transfer of newly learned neutral material. Previous studies on
      this subject are reviewed and a pilot study with four subjects is described. This
      study is specifically concerned with the question whether self-reported
      asymmetries in between-identity transfer can be replicated on experimental memory
      tests. A secondary aim was to examine whether, in the absence of explicit
      transfer, implicit transfer of information would occur. The results showed that
      the apparent amnestic asymmetry for explicit information was substantiated in the
      laboratory, although at least some leakage was present between the apparently
      amnestic identities. No evidence was found for better performance on implicit
      than on explicit memory tests in the apparently amnestic identities. In the
      discussion, parallels between apparent amnesia in DID and state-dependent memory
      are drawn, and the question of simulated amnesia is addressed.

PMID- 9521831
TI  - Neuronal phenomena associated with vigilance and consciousness: from cellular
      mechanisms to electroencephalographic patterns.
AB  - The neuroanatomical substrates controlling and regulating sleeping and waking,
      and thus consciousness, are located in the brain stem. Most crucial for bringing
      the brain into a state conducive for consciousness and information processing is
      the mesencephalic part of the brain stem. This part controls the state of waking,
      which is generally associated with a high degree of consciousness. Wakefulness is
      accompanied by a low-amplitude, high-frequency electroencephalogram, due to the
      fact that thalamocortical neurons fire in a state of tonic depolarization.
      Information can easily pass the low-level threshold of these neurons, leading to
      a high transfer ratio. The complexity of the electroencephalogram during
      conscious waking is high, as expressed in a high correlation dimension.
      Accordingly, the level of information processing is high. Spindles, and alpha
      waves in humans, mark the transition from wakefulness to sleep. These phenomena
      are related to drowsiness, associated with a reduction in consciousness.
      Drowsiness occurs when cells undergo moderate hyperpolarizations. Increased
      inhibitions result in a reduction of afferent information, with a lowered
      transfer ratio. Information processing subsides, which is also expressed in a
      diminished correlation dimension. Consciousness is further decreased at the onset
      of slow wave sleep. This sleep is controlled by the medullar reticular formation
      and is characterized by a high-voltage, low-frequency electroencephalogram. Slow
      wave sleep becomes manifest when neurons undergo a further hyperpolarization.
      Inhibitory activities are so strong that the transfer ratio further drops, as
      does the correlation dimension. Thus, sensory information is largely blocked and
      information processing is on a low level. Finally, rapid eye movement sleep is
      regulated by the pontine reticular formation and is associated with a "wake-like"
      electroencephalographic pattern. Just as during wakefulness, this is the
      expression of a depolarization of thalamocortical neurons. The transfer ratio of
      rapid eye movement sleep has not yet been determined, but seems to vary. Evidence
      exists that this type of sleep, associated with dreaming, with some kind of
      perception and consciousness, is involved in processing of "internal"
      information. In line with this, rapid eye movement sleep has higher correlation
      dimensions than slow-wave sleep and sometimes even higher than wakefulness. It is
      assumed that the "near-the-threshold" depolarized state of neurons in the
      thalamus and cerebral cortex is a necessary condition for perceptual processes
      and consciousness, such as occurs during waking and in an altered form during
      rapid eye movement sleep.

PMID- 9521832
TI  - An electrophysiological measure of priming of visual word-form.
AB  - Priming and recollection are expressions of human memory mediated by different
      brain events. These brain events were monitored while people discriminated words
      from nonwords. Mean response latencies were shorter for words that appeared in an
      earlier study phase than for new words. This priming effect was reduced when the
      letters of words in study-phase presentations were presented individually in
      succession as opposed to together as complete words. Based on this outcome,
      visual word-form priming was linked to a brain potential recorded from the scalp
      over the occipital lobe about 450 ms after word onset. This potential differed
      from another potential previously associated with recollection, suggesting that
      distinct operations associated with these two types of memory can be monitored at
      the precise time that they occur in the human brain.

PMID- 9521833
TI  - Eyelid movements and mental activity at sleep onset.
AB  - The nature and time course of sleep onset (hypnagogic) mentation was studied in
      the home environment using the Nightcap, a reliable, cost-effective, and
      relatively noninvasive sleep monitor. The Nightcap, linked to a personal
      computer, reliably identified sleep onset according to changes in perceived
      sleepiness and the appearance of hypnagogic dream features. Awakenings were
      performed by the computer after 15 s to 5 min of sleep as defined by eyelid
      quiescence. Awakenings from longer periods of sleep were associated with (1) an
      increase in reported sleepiness, (2) a decrease in the length of mentation
      reports, (3) a decrease in the frequency of reports of normal, wake-like
      thoughts, (4) an increase in the frequency of "unusual thoughts," and (5)
      increased frequencies of formal dream features, including visual hallucination,
      self-representation, fictive movement, narrative plot, and bizarreness. While
      sleep-onset reports can include all features of rapid eye movement (REM) dream
      reports, the number of such features is markedly reduced at sleep onset,
      suggesting that this mentation is a greatly diminished version of REM dreaming.

PMID- 9521834
TI  - The mere exposure effect is differentially sensitive to different judgment tasks.
AB  - The mere exposure effect is the increase in positive affect that results from the
      repeated exposure to previously novel stimuli. We sought to determine if
      judgments other than affective preference could reliably produce a mere exposure
      effect for two-dimensional random shapes. In two experiments, we found that
      brighter and darker judgments did not differentiate target from distracter
      shapes, liking judgments led to target selection greater than chance, and
      disliking judgments led to distracter selection greater than chance. These
      results for brighter, darker, and liking judgments were obtained regardless of
      whether shape recognition was greater (Experiment 1) or not greater (Experiment
      2) than chance. Effects of prior exposure to novel shapes were reliably observed
      only for affective judgment tasks. These results are inconsistent with general
      predictions made by the nonspecific activation hypothesis, but not the affective
      primacy or perceptual fluency hypotheses which were discussed in terms of
      cognitive neuroscience research.

PMID- 9521836
TI  - Conference on neural correlates of consciousness: empirical and conceptual
      questions 
AB  - Copyright

PMID- 9521835
TI  - On the utility of the signal detection model of the remember-know paradigm.

PMID- 9521838
TI  - The association of tau-like proteins with vimentin filaments in cultured cells.
AB  - There is increasing evidence that the different polymers that constitute the
      cytoskeleton are interconnected to form a three-dimensional network. The
      macromolecular interaction patterns that stabilize this network and its intrinsic
      dynamics are the basis for numerous cellular processes. Within this context, in
      vitro studies have pointed to the existence of specific associations between
      microtubules, microfilaments, and intermediate filaments. It has also been
      postulated that microtubule-associated proteins (MAPs) are directly involved in
      mediating these interactions. The interactions of tau with vimentin filaments,
      and its relationships with other filaments of the cytoskeletal network, were
      analyzed in SW-13 adenocarcinoma cells, through an integrated approach that
      included biochemical and immunological studies. This cell line has the advantage
      of presenting a wild-type clone (vim+) and a mutant clone (vim-) which is
      deficient in vimentin expression. We analyzed the cellular roles of tau, focusing
      on its interactions with vimentin filaments, within the context of its functional
      aspects in the organization of the cytoskeletal network. Cosedimentation
      experiments of microtubular protein with vimentin in cell extracts enriched in
      intermediate filaments, combined with studies on the direct interaction of tau
      with nitrocellulose-bound vimentin and analysis of tau binding to vimentin
      immobilized in single-strand DNA affinity columns, indicate that tau interacts
      with the vimentin network. These studies were confirmed by a quantitative
      analysis of the immunofluorescence patterns of cytoskeleton-associated tubulin,
      tau, and vimentin using flow cytometry. In this regard, a decrease in the levels
      of tau associated to the cytoskeletal network in the vim- cell mutant compared
      with the wild-type clones was observed. However, immunofluorescence data on SW-13
      cells suggest that the absence of a structured network of vimentin in the mutant
      vim- cells does not affect the cytoplasmic organization formed by microtubules
      and actin filaments, when compared with the wild-type vim+ cells. These studies
      suggest that tau associates with vimentin filaments and that these interactions
      may play a structural role in cells containing these filaments.

PMID- 9521837
TI  - Apoptosis, excitotoxicity, and neuropathology.
AB  - While a high rate of cell loss is tolerated and even required to model the
      developing nervous system, an increased rate of cell death in the adult nervous
      system underlies neurodegenerative disease. Evolutionarily conserved mechanisms
      involving proteases, Bcl-2-related proteins, p53, and mitochondrial factors
      participate in the modulation and execution of cell death. In addition, specific
      death mechanisms, based on specific neuronal characteristics such as excitability
      and the presence of specific channels or enzymes, have been unraveled in the
      brain. Particularly important for various human diseases are excessive nitric
      oxide (NO) production and excitotoxicity. These two pathological mechanisms are
      closely linked, since excitotoxic stimulation of neurons may trigger enhanced NO
      production and exposure of neurons to NO may trigger the release of excitotoxins.
      Depending on the experimental situation and cell type, excitotoxic neuronal death
      may either be apoptotic or necrotic.

PMID- 9521839
TI  - Formation of postsynaptic-like membranes during differentiation of embryonic stem
      cells in vitro.
AB  - To analyze the formation of neuromuscular junctions, mouse pluripotent embryonic
      stem (ES) cells were differentiated via embryoid bodies into skeletal muscle and
      neuronal cells. The developmentally controlled expression of skeletal muscle
      specific genes coding for myf5, myogenin, myoD and myf6, alpha 1 subunit of the L
      type calcium channel, cell adhesion molecule M-cadherin, and neuron-specific
      genes encoding the 68-, 160-, and 200-kDa neurofilament proteins, synaptic
      vesicle protein synaptophysin, brain-specific proteoglycan neurocan, and
      microtubule-associated protein tau was demonstrated by RT-PCR analysis. In
      addition, genes specifically expressed at neuromuscular junctions, the gamma- and
      epsilon-subunits of the nicotinic acetylcholine receptor (AChR) and the
      extracellular matrix protein S-laminin, were found. At the terminal
      differentiation stage characterized by the formation of multinucleated
      spontaneously contracting myotubes, the myogenic regulatory gene myf6 and the
      AChR epsilon-subunit gene, both specifically expressed in mature adult skeletal
      muscle, were found to be coexpressed. Only the terminally differentiated myotubes
      showed a clustering of nicotinic acetylcholine receptors (AChR) and a
      colocalization with agrin and synaptophysin. The formation of AChRs was also
      demonstrated on a functional level by using the patch clamp technique. Taken
      together, our results showed that during ES cell differentiation in vitro neuron-
      and muscle-specific genes are expressed in a developmentally controlled manner,
      resulting in the formation of postsynaptic-like membranes. Thus, the embryonic
      stem cell differentiation model will be helpful for studying cellular
      interactions at neuromuscular junctions by "loss of function" analysis in vitro.

PMID- 9521840
TI  - Subcellular distribution of distinct nucleolin subfractions recognized by two
      monoclonal antibodies.
AB  - Monoclonal antibodies binding to different domains of nucleolin have been used to
      localize nucleolin in tissue culture cells of Xenopus laevis. The monoclonal
      antibody b6-6E7 binds to an epitope in the N-terminal domain, which contains
      arrays of phosphorylation consensus sites. This monoclonal antibody binds to
      nucleolin of oocytes and of eggs with high affinity. In contrast, the monoclonal
      antibody Nu-1H6 binds poorly to the modified forms of nucleolin arising during
      meiosis and mitosis. In interphase cells, monoclonal antibody b6-6E7
      preferentially stains the periphery of the nucleoli, where most of the rRNA
      accumulates. Staining by monoclonal antibody Nu-1H6 complements this pattern by
      staining mainly the center of the nucleoli. The epitope of monoclonal antibody Nu
      1H6 is within the central domain of nucleolin, which contains the first two RNA
      binding domains. RNase treatment of cells results in loss of nucleolin from
      nucleoli. In mitotic cells, both monoclonal antibodies decorate the surface of
      condensing chromosomes in prophase. The periphery of the condensed chromosomes in
      metaphase and anaphase is preferentially stained by monoclonal antibody b6-6E7.

PMID- 9521841
TI  - Differences in elasticity of vinculin-deficient F9 cells measured by magnetometry
      and atomic force microscopy.
AB  - We have investigated a mouse F9 embryonic carcinoma cell line, in which both
      vinculin genes were inactivated by homologous recombination, that exhibits
      defective adhesion and spreading [Coll et al. (1995) Proc. Natl. Acad. Sci. USA
      92, 9161-9165]. Using a magnetometer and RGD-coated magnetic microbeads, we
      measured the local effect of loss and replacement of vinculin on mechanical force
      transfer across integrins. Vinculin-deficient F9Vin(-/-) cells showed a 21%
      difference in relative stiffness compared to wild-type cells. This was restored
      to near wild-type levels after transfection and constitutive expression of
      increasing amounts of vinculin into F9Vin(-/-) cells. In contrast, the
      transfection of vinculin constructs deficient in amino acids 1-288 (containing
      the talin- and alpha-actinin-binding site) or substituting tyrosine for
      phenylalanine (phosphorylation site, amino acid 822) in F9Vin(-/-) cells resulted
      in partial restoration of stiffness. Using atomic force microscopy to map the
      relative elasticity of entire F9 cells by 128 x 128 (n = 16,384) force scans, we
      observed a correlation with magnetometer measurements. These findings suggest
      that vinculin may promote cell adhesions and spreading by stabilizing focal
      adhesions and transferring mechanical stresses that drive cytoskeletal
      remodeling, thereby affecting the elastic properties of the cell.

PMID- 9521842
TI  - The interaction of Mip-90 with microtubules and actin filaments in human
      fibroblasts.
AB  - The novel microtubule-interacting protein Mip-90 was originally isolated from
      HeLa cells by using affinity columns of agarose derivatized with peptides from
      the C-terminal regulatory domain on beta-tubulin. Biochemical and
      immunocytochemical data have suggested that the association of Mip-90 with the
      microtubule system contributes to its cellular organization. Here we report the
      interaction patterns of Mip-90 with microtubules and actin filaments in
      interphase human fibroblasts. A polyclonal monospecific antibody against Mip-90
      was used for immunofluorescence microscopy analysis to compare the distribution
      patterns of this protein with tubulin and actin. A detailed observation of
      fibroblasts revealed the colocalization of Mip-90 with microtubules and actin
      filaments. These studies were complemented with experiments using cytoskeleton
      disrupting drugs which showed that colocalization patterns of Mip-90 with
      microtubules and actin filaments requires the integrity of these cytoskeletal
      components. Interestingly, a colocalization of Mip-90 with actin at the leading
      edge of fibroblasts grown under subconfluency was observed, suggesting that Mip
      90 could play a role in actin organization, particularly at this cellular domain.
      Mip-90 interaction with actin polymers was further supported in vitro by
      cosedimentation and immunoprecipitation experiments. The cosedimentation analysis
      indicated that Mip-90 bound to actin filaments with an association constant Ka =
      1 x 10(6) M-1, while an stoichiometry Mip-90/actin of 1:12 mol/mol was
      calculated. Western blots of the immunoprecipitates revealed that Mip-90
      associated to both actin and tubulin in fibroblasts extracts. These studies
      indicate that Mip-90, described as a microtubule-interacting protein, also bears
      the capacity to interact with the microfilament network, suggesting that it may
      play a role in modulating the interactions between these cytoskeletal filaments
      in nonneuronal cells.

PMID- 9521843
TI  - Response of lens epithelial cells to hydrogen peroxide stress and the protective
      effect of caloric restriction.
AB  - Hydrogen peroxide (H2O2) has been reported to be present at significant levels in
      the lens and aqueous humor in some cataract patients and suggested as a possible
      source of chronically inflicted damage to lens epithelial (LE) cells. We measured
      H2O2 effects on bovine and mouse LE cells and determined whether LE cells from
      old calorically restricted mice were more resistant to H2O2-induced cellular
      damage than those of same age ad libitum fed (AL) mice. Bovine lens epithelial
      cells were exposed to H2O2 at 40 or 400 microM for 2 h and then allowed to
      recover from the stress. The cells were assayed for DNA damage, DNA synthesis,
      cell viability, cell morphology, response to growth stimuli, and proliferation
      potential. Hydrogen peroxide-treated cells showed an increased DNA unwinding 50%
      greater than that for untreated controls. These DNA strand breaks appeared to be
      almost completely rejoined by 30 min following removal of the cells from a 2-h
      exposure. The 40 microM exposure did not produce a significantly lower DNA
      synthesis rate than the control, it responded to growth factor stimuli, and it
      replicated as did the control cells after removal of H2O2. The 400 microM H2O2
      severely affected DNA synthesis and replication, as shown by increased cell size
      and by markedly reduced clonal cell growth. The cells did not respond to growth
      stimulation by serum or growth factors and lost irreversibly the capacity to
      proliferate. The responses of LE cells from old adlib diet (AL) and calorically
      restricted (CR) mice to H2O2 were significantly different. Exposure of LE cells
      to 20, 40, or 100 microM H2O2 for 1 h induces a significant loss of cellular
      proliferation in cells from old AL mice. LE cells from long-term CR mice of the
      same strain and age were more resistant to oxidative damage at all three
      concentrations of H2O2 than those of both old and young AL mice and showed a
      significantly higher proliferation potential following treatment. It is concluded
      that CR results in superior resistance to reactive oxygen radicals in the lens
      epithelium.

PMID- 9521844
TI  - Induction of retinoblastoma gene expression during terminal growth arrest of a
      conditionally immortalized fetal rat lung epithelial cell line and during fetal
      lung maturation.
AB  - The process by which fetal lung epithelial cells differentiate into type 1 and
      type 2 cell is largely unknown. In order to study lung epithelial cell
      proliferation and differentiation we have infected 20-day fetal lung epithelial
      cells with a retrovirus carrying a temperature-sensitive SV40 T antigen (T Ag)
      and isolated several immortalized fetal epithelial cell lines. Cell line 20-3 has
      characteristics of lung epithelial cells including the presence of distinct
      lamellar bodies, tight junctions, keratin 8 and 18 mRNA, HFH8, and T1 alpha mRNA
      and low levels of surfactant protein A mRNA. At 33 degrees C 20-3 grows with a
      doubling time of 21 h. At 40 degrees C the majority of cells cease to
      proliferate. Growth arrest is accompanied by significant morphological changes
      including an increase in cell size, transition to a squamous phenotype that
      resembles type 1 cells, and an increase in the number of multinucleated cells
      within the population. Greater than 95% of the cells incorporate [3H]thymidine
      into DNA at 33 degrees C whereas at 40 degrees C label incorporation drops to
      less than 20%. When shifted down to 33 degrees C 40% of the cells remain
      terminally growth arrested. In addition, cells plated at 40 degrees C have a
      reduced ability to form colonies when replated at 33 degrees C. Treatment with
      TGF-beta increases the percentage of cells that terminally growth arrest to
      greater than 80%. Growth arrest is accompanied by an increase in the levels of c
      jun, jun D, cyclin D1, C/EBP-beta, transglutaminase type II, and retinoblastoma
      (Rb) mRNA and an induction of p105, the hypophosphorylated, growth regulatory
      form of Rb. Evaluation of Rb mRNA in fetal lung indicates that it is induced 2.5
      fold between 17 and 21 days of gestation. These studies indicate that 20-3
      terminally growth arrests in culture at the nonpermissive temperature and that it
      may be useful in studying changes in gene expression that accompany terminal
      growth arrest during lung development.

PMID- 9521845
TI  - Distinct alterations in mitochondrial mass and function characterize different
      models of apoptosis.
AB  - Recent studies have shown that reduction in mitochondrial membrane potential
      (delta psi m) and generation of reactive oxygen species are early events in
      apoptosis. In this study, we present two different models of apoptotic cell
      death, Chinese hamster ovary (CHO) cells treated with aphidicolin and
      dexamethasone-treated 2B4 T-cell hybridoma cells, which display opposing
      mitochondrial changes. CHO cells arrested at G1/S with aphidicolin have a
      progressive increase in mitochondria mass and number, assessed by flow cytometry
      and fluorescent microscopy with mitochondria-specific probes. The increase in
      mitochondrial mass was not accompanied by a gain in net cellular mitochondrial
      membrane potential, consistent with an accumulation of relatively depolarized
      mitochondria. Fluorescent microscopy demonstrated an increased content of low
      delta psi m mitochondria in aphidicolin-treated CHO cells, but high delta psi m
      mitochondria were also present and remained stable in number. Mitochondrial mass
      correlated with decreased clonogenicity of aphidicolin-treated CHO cells.
      Cycloheximide prevented both the proliferation of mitochondria and subsequent
      cell death. In contrast, dexamethasone treatment of 2B4 T-cell hybridoma cells
      caused a decrease in delta psi m without mitochondrial proliferation.
      Cycloheximide and Bcl-2 overexpression inhibited the loss of delta psi m, as well
      as apoptosis. In both models, cell death was associated with a decrease in
      mitochondrial potential relative to mitochondrial mass, suggesting that an
      accumulation of damaged or dysfunctional mitochondria had occurred.

PMID- 9521846
TI  - Expression of mutant dynamin protects cells against diphtheria toxin but not
      against ricin.
AB  - Diphtheria toxin is believed to enter sensitive mammalian cells via receptor
      mediated endocytosis from clathrin-coated pits, while ricin can enter via both
      clathrin-dependent and clathrin-independent endocytosis. The present study has
      confirmed this by determining the toxin sensitivity of COS-7y cells which were
      transiently overexpressing a trans dominant negative mutant of dynamin, a GTPase
      required for the budding of clathrin-coated vesicles from the plasma membrane.
      Cells overexpressing wild-type dynamin showed normal receptor-mediated
      endocytosis of transferrin and remained sensitive to both diphtheria toxin and
      ricin. Cells overexpressing a mutant dynamin defective in GTP binding and
      hydrolysis were unable to endocytose transferrin and were protected against
      diphtheria toxin, but they remained completely sensitive to ricin intoxication.
      Treating non-transfected cells or cells overexpressing mutant dynamin with
      nystatin caused a redistribution of the caveolae membrane marker protein VIP21
      caveolin from the cell surface to intracellular locations, but did not affect
      their sensitivity to ricin. The redistribution of caveolin seen after nystatin
      treatment may reflect the disappearance of caveolae. If this is the case,
      caveolae are not responsible for the endocytosis of ricin. An alternative
      clathrin-independent route may operate for ricin, since cellular uptake,
      intracellular transport, and translocation into the cytosol remain unaffected
      when clathrin-dependent endocytosis is effectively blocked.

PMID- 9521848
TI  - Integrin alpha 5 beta 1 expression is required for inhibition of keratinocyte
      migration by ganglioside GT1b.
AB  - Polysialoganglioside GT1b, a keratinocyte membrane glycosphingolipid, inhibits
      normal keratinocyte adhesion and migration on a fibronectin matrix. The
      specificity of the inhibition for cells plated on a fibronectin matrix and
      competition of GT1b inhibition with peptide RGDS suggest that GT1b abrogates the
      alpha 5 beta 1/fibronectin interaction. We examined the effects of GT1b on the
      adhesion and migration of keratinocyte-derived cell lines and correlated GT1b
      responsiveness and alpha 5 beta 1 integrin expression. GT1b (5 nM) significantly
      inhibited migration of normal human keratinocytes, immortalized keratinocytes,
      and squamous cell carcinoma SCC12F2 cells on fibronectin, but not on collagen I.
      Concentrations as high as 5 microM had no effect on SCC13 or HaCaT cells.
      Likewise, GT1b inhibited fibronectin-dependent cell adhesion of normal human
      keratinocytes, immortalized keratinocytes, and SCC12F2 cells, but had no effect
      on SCC13 or HaCaT cells. Flow cytometric and Western immunoblot analysis of
      integrin expression showed significantly decreased alpha 5 and beta 1 integrin
      expression in SCC13 and HaCaT cells compared to normal keratinocytes,
      immortalized keratinocytes, and SCC12F2 cells. Incubation with TGF-beta 1
      increased alpha 5 beta 1 integrin expression and induced responsiveness to GT1b
      in HaCaT cells. These data imply that GT1b "response" requires sufficient
      expression of alpha 5 beta 1 and further suggest that the mechanism of the
      inhibitory effect of GT1b involves GT1b/alpha 5 beta 1 interaction.

PMID- 9521847
TI  - Sulfated glycosaminoglycans enhance tumor cell invasion in vitro by stimulating
      plasminogen activation.
AB  - Metastasizing tumor cells invade host tissues by degrading extracellular matrix
      constituents. We report here that the highly sulfated glycosaminoglycans, heparin
      and heparan sulfate, as well as the sulfated polysaccharide, fucoidan,
      significantly enhanced tumor cell invasion in vitro into fibrin, the basement
      membrane extract, Matrigel, or through a basement membrane-like extracellular
      matrix. The enhancement of tumor cell invasion was due to a stimulation of the
      proteolytic cascade of plasminogen activation since the effect required
      plasminogen activation and was abolished by inhibitors of urokinase-type
      plasminogen activator (uPA) or plasmin. Sulfated polysaccharides enhanced five
      reactions of tumor-cell initiated plasminogen activation in a dose-dependent
      manner. They amplified plasminogen activation in culture supernatants up to 70
      fold by stimulating (i) pro-uPA activation by plasmin and (ii) plasminogen
      activation by uPA. (iii) In addition, sulfated polysaccharides partially
      protected plasmin from inactivation by alpha 2-antiplasmin. Sulfated
      polysaccharides also stimulated tumor-cell associated plasminogen activation,
      e.g., (iv) cell surface pro-uPA activation by plasmin and (v) plasminogen
      activation by cell surface uPA. These results suggest that sulfated
      glycosaminoglycans liberated by tumor-cell mediated extracellular matrix
      degradation in vivo might amplify pericellular plasminogen activation and locally
      enhance tumor cell invasion in a positive feedback manner.

PMID- 9521850
TI  - Focal adhesion kinase pp125FAK and the beta 1 integrin subunit are constitutively
      complexed in HaCaT cells.
AB  - Binding of integrins to the extracellular matrix (ECM) activates various signal
      transduction pathways and regulates gene expression in many cell types. Integrin
      dependent cytoplasmic protein/protein interactions are necessary for activation
      of those signal transduction cascades. In our studies we investigated a possible
      association of pp125FAK, an adhesion involved tyrosine kinase, with the integrin
      beta 1 subunit. Further we wanted to know to which extent protein tyrosine
      phosphorylation affects cell adhesion to the ECM and the possible beta 1
      integrin/pp125FAK complex. We were able to show that in HaCaT cells (a human
      keratinocyte derived cell line) the integrin beta 1 subunit is associated with
      tyrosine kinase pp125FAK. This association was observed in ECM-adherent cells and
      nonadherent cells and is independent of tyrosine phosphorylation. However, cell
      adhesion of HaCaT cells to specific substrates requires tyrosine phosphorylation
      since genistein treatment that blocks phosphorylation of many cellular proteins
      as pp125FAK led to a reduced substrate adhesion.

PMID- 9521849
TI  - A putative G-protein-coupled receptor, H218, is down-regulated during the
      retinoic acid-induced differentiation of F9 embryonal carcinoma cells.
AB  - We have previously cloned a novel guanine nucleotide-binding protein (G-protein)
      coupled receptor, H218, that has sequence similarity to a lysophosphatidic acid
      receptor, edg2. We present here Northern analysis indicating that the H218 mRNA
      is expressed in undifferentiated F9 embryonal carcinoma cells. The H218 message
      is down-regulated and its stability is decreased during retinoic acid- and
      dibutyryl cAMP-induced differentiation. Treatment by various receptor-selective
      retinoids indicated that retinoic acid receptor beta or gamma signaling, but not
      retinoid X receptor activation, is required for the down-regulation of H218 mRNA.
      Activation of the H218 receptor may contribute to the phenotype of
      undifferentiated F9 embryonal carcinoma cells.

PMID- 9521851
TI  - GFAP-deficient astrocytes are capable of stellation in vitro when cocultured with
      neurons and exhibit a reduced amount of intermediate filaments and an increased
      cell saturation density.
AB  - Glial fibrillary acidic protein (GFAP) is an intermediate filament protein
      predominantly expressed in cells of astroglial origin. To allow for the study of
      the biological functions of GFAP we have previously generated GFAP-negative mice
      by gene targeting [Pekny et al. (1995) EMBO J. 14, 1590-1598]. Astrocytes in
      culture, similar to reactive astrocytes in vivo, express three intermediate
      filament proteins: GFAP, vimentin, and nestin. Using primary astrocyte-enriched
      cultures from GFAP-negative mice, we now report on the effect of GFAP absence on
      (i) the synthesis of other intermediate filament proteins in astrocytes, (ii)
      intermediate filament formation, (iii) astrocyte process formation (stellation)
      in response to neurons in mixed cerebellar astrocyte/neuron cultures, and (iv)
      saturation cell density in vitro. GFAP-/- astrocytes were found to produce both
      nestin and vimentin. At the ultrastructural level, the amount of intermediate
      filaments as revealed by transmission electron microscopy was reduced in GFAP-/-
      astrocytes compared to that in GFAP+/+ astrocytes. GFAP-/- astrocytes retained
      the ability to form processes in response to neurons in mixed astrocyte/neuron
      cultures from the cerebellum. GFAP-/- astrocyte-enriched primary cultures
      exhibited an increased final cell saturation density. The latter leads us to
      speculate that the loss of GFAP expression observed focally in a proportion of
      human malignant gliomas may reflect tumor progression toward a more rapidly
      growing and malignant phenotype.

PMID- 9521852
TI  - Melanosomal defects in melanocytes from mice lacking expression of the pink-eyed
      dilution gene: correction by culture in the presence of excess tyrosine.
AB  - Mutations in the murine pink-eyed dilution (p) gene, or its human homologue P,
      result in oculocutaneous albinism. Melanocytes cultured from mice lacking p gene
      expression exhibit defective melanogenesis, but following culture in the presence
      of high concentrations of L-tyrosine, increased melanin deposition is observed.
      Electron microscopy and image analysis demonstrated that untreated p mutant
      melanocytes exhibited small melanosomes, largely of stages I-II. Following
      tyrosine treatment, increased proportions of stage III-IV melanosomes, almost
      normal in size, were observed. Levels of tyrosinase protein and to a lesser
      extent of tyrosinase-related protein-1 (TRP-1) were subnormal but rose
      dramatically following stimulation by tyrosine. Levels of TRP-2 and Pmel17/silver
      gene product were not altered, nor were the levels of mRNA for tyrosinase, TRP-1,
      TRP-2, or the Pmel17/silver gene product. As expected, the 110-kDa product of the
      p gene was absent from both stimulated and unstimulated p mutant cells. In a
      melanoblast line derived from the same mice, excess tyrosine failed to stimulate
      visible melanogenesis or increase the low levels of tyrosinase. The melanosomes
      in these cells were smaller still than those in the mutant melanocytes even when
      cultured in the presence of excess tyrosine. Thus, absence of the p gene product
      affects melanosomal structure and protein composition at the posttranscriptional
      level. These defects are correctable at least in part by supplementation with L
      tyrosine.

PMID- 9521853
TI  - Mechanical strain increases protein tyrosine phosphorylation in airway smooth
      muscle cells.
AB  - Mechanical stress contributes to normal structure and function of the lung as
      well as pathology in such diseases as bronchopulmonary dysplasia and adult
      respiratory distress syndrome. Stress-related increases in airway smooth muscle
      (ASM) quantity are reflected in vitro where cultured ASM cells respond to cyclic
      deformational strain with increased proliferation, cell reorientation, protein
      production, stress fibers, and focal adhesions. To understand the mechanisms of
      mechanical signaling in ASM cells, we investigated whether strain increased
      tyrosine phosphorylation of focal adhesion-related proteins. ASM cells were grown
      to confluence on collagen type I and subjected to 30 min of cyclic deformation
      strain (2 s of 25% deformation of the substratum, 2 s relaxation) and compared at
      various time points with identical cells not subjected to strain for
      phosphotyrosine content of three focal adhesion-concentrated proteins (pp125FAK,
      paxillin, and talin) by Western blotting. Strain caused a rapid increase in
      tyrosine phosphorylation of pp125FAK and paxillin. Tyrosine phosphorylation
      decreased by 4 h in pp125FAK after discontinuing strain but remained elevated in
      paxillin at 24 h. Increases in tyrosine phosphorylation of talin were not found.
      In separate studies, when cells were strained in the presence of tyrosine kinase
      inhibitors (genistein and herbimycin A), strain-induced reorientation and
      elongation were inhibited. Mechanochemical signal transduction appears to mediate
      cell morphologic changes through quantitative and possibly qualitative changes in
      tyrosine phosphorylation of adhesion-related proteins.

PMID- 9521855
TI  - Telomere length dynamics in telomerase-positive immortal human cell populations.
AB  - It has been proposed that the progressive shortening of telomeres in somatic
      cells eventually results in senescence. Previous experiments have demonstrated
      that many immortal cell lines have acquired telomerase activity leading to
      stabilization of telomere length. Telomere dynamics and telomerase activity were
      examined in the telomerase-positive immortal cell lines HeLa and 293 and
      subclones derived from them. A mass culture of HeLa cells had a stable mean
      telomere length over 60 population doublings (PD) in vitro. Subclones of this
      culture, however, had a range of mean telomere lengths indicating that telomeric
      heterogeneity exists within a population with a stable mean telomere length. Some
      of the subclones lacked detectable telomerase activity soon after isolation but
      regained it by PD 18, suggesting that at least some of the variation in telomere
      length can be attributed to variations in telomerase activity levels. 293
      subclones also varied in telomere length and telomerase activity. Some telomerase
      positive 293 subclones contained long telomeres that gradually shortened,
      demonstrating that factors other than telomerase also act to modulate telomere
      length. Fluctuations in telomere length in telomerase-positive immortalized cells
      may contribute to chromosomal instability and clonal evolution.

PMID- 9521854
TI  - Accelerated proliferative senescence of rat embryo fibroblasts after stable
      transfection of multiple copies of the c-Myc DNA-binding sequence.
AB  - The protooncogene c-myc positively regulates cellular proliferation whereas it
      exhibits negative effects on both cellular senescence and differentiation.
      Ectopic overexpression of c-myc in transfection experiments or titration of the c
      myc mRNA by antisense oligonucleotides has demonstrated that small changes of the
      concentration of cellular c-myc mRNA or protein levels can be crucial for these
      processes. In view of the role of c-Myc as a transcription factor, most of these
      effects may be mediated via its binding to specific DNA sequences. Here we
      studied the cellular reactions after manipulating the cellular concentration of c
      Myc DNA-binding sites. Multiple copies of the c-Myc-binding sequence GACCACGTGGTC
      or, alternatively, the control sequence GACCAGCTGGTC that displays only a poor
      affinity for c-Myc were stably introduced into the genome of rat embryo
      fibroblasts. Transfection with the c-Myc-binding sequence yielded much lower
      clone numbers and sizes than transfection with the control sequence. After
      polyclonal selection and further subcultivation cells transfected with c-Myc
      binding sequence exhibited a reduced growth rate and achieved less than two
      thirds of the cumulative population doublings before becoming senescent and
      irreversibly growth arrested compared to the controls. Southern blot analysis
      demonstrated that 30 binding sequences on average were integrated into the
      cellular genome. Our results can be interpreted as competition of the ectopically
      introduced c-Myc-binding sequences with the functional genomic ones and assume
      that a fairly low number of the latter exist in the normal cellular genome.
      Hence, only a low copy number of introduced c-Myc-binding sequences is sufficient
      to cause signs of accelerated proliferative senescence.

PMID- 9521856
TI  - Ultrastructural localization of interferon-inducible double-stranded RNA
      activated enzymes in human cells.
AB  - The protein kinase PKR and the 2',5'-oligoadenylate (2-5A) synthetase are two
      interferon-induced and double-stranded RNA-activated enzymes which are implicated
      in the mechanism of action of interferon. Their distribution was undertaken here
      at the ultrastructural level by the immunogold procedure, following the use of
      specific monoclonal antibodies directed against PKR and 69- and 100-kDa forms of
      the 2-5A synthetase. These enzymes were detected as a pool of nonaggregated
      proteins scattered throughout the cell and as aggregates often associated with
      electron-dense doughnut-like structures showing a similar aspect whatever their
      subcellular localization: the cytoplasm, the nuclear envelope, and the nucleus.
      In general, the 2-5A synthetases were present in much more lower amounts than the
      PKR, probably due to the difficulty of detecting traces of proteins by electron
      microscopy. To circumvent this, we used a human lymphoblastoid cell line
      overexpressing the 69-kDa form of the 2-5A synthetase. In such cells, the
      synthetase was then clearly observed in both the cytoplasm and the nucleus;
      isolated or small clusters of gold particles were numerous in the cell mainly
      over the RNP fibrils of the interchromatin space, nucleolus, and ribosomes.
      Interestingly, gold particles were also found to be associated with the membranes
      of nuclear envelope and rough endoplasmic reticulum probably due to the
      myristilated motif of this form of 2-5A synthetase. Finally, intensely labeled
      electron-opaque dots sometimes associated with the nuclear pore complexes were
      present in the nucleus and in the cytoplasm of cells which might suggest their
      transport from the nucleus to the cytoplasm or reciprocally through the nuclear
      pore complexes. These observations indicate the wider distribution of the dsRNA
      activated enzymes in the cell, thus pointing out their potential implication in
      as yet undetermined physiological function(s) necessary for various cellular
      metabolic reactions.

PMID- 9521857
TI  - Micromolar zinc affects endonucleolytic activity in hydrogen peroxide-mediated
      apoptosis.
AB  - When damaged by hydrogen peroxide, peripheral blood lymphocytes undergo cell
      death by apoptosis in the absence of internucleosomal DNA cleavage, while, in the
      same cells, other apoptosis-inducing treatments bring DNA cleavage to completion.
      However, the formation of internucleosomal DNA fragments is readily obtained if
      cells are pretreated with a divalent metal chelator, TPEN, at micromolar
      concentrations. Since the coadministration of equimolar zinc concentrations
      abrogates the formation of the ladder, a zinc-inhibitable endonucleolytic
      activity is accounted for the effect. Most notably, subtraction of zinc ions does
      not increase the percentage of cells undergoing apoptosis, but rather results in
      a rescue from death.

PMID- 9521858
TI  - Dynamics of basement membrane formation by keratinocyte-fibroblast interactions
      in organotypic skin culture.
AB  - The cutaneous basement membrane zone, composed of numerous macromolecules, plays
      a multifunctional role in tissue regeneration and maintenance. To elucidate the
      cellular origin and dynamics of basement membrane formation, de novo synthesis,
      deposition, and ultrastructural assembly of its components were analyzed in
      organotypic cultures of adult skin keratinocytes on collagen gels with or without
      collagen-embedded dermal cells. Collagen IV and laminin-1 deposition occurred
      only in the presence of mesenchymal cells: patchy at day 4 and continuous after 1
      week. Chain-specific mRNA expression started at day 2 in both keratinocytes and
      fibroblasts. It steadily increased up to day 10, however, with a reciprocal
      induction pattern, mRNA abundance shifting from keratinocytes to fibroblasts. On
      the other hand, laminin-5 staining was first observed at day 4, but in
      keratinocyte both mono- and cocultures. This was followed by nidogen, which was
      detected in cocultures but also in dermal monocultures. Laminin-5 protein
      persisted throughout day 21, whereas nidogen steadily increased in intensity.
      Expression kinetics revealed high levels of laminin-5 transcripts early and in
      keratinocytes only, whereas nidogen was expressed later and predominantly in
      fibroblasts. Although basement membrane protein deposition was continuous at day
      14, the ultrastructural organization was still fragmentary, eventually
      normalizing at 3 weeks. These data demonstrate a dynamic interaction and
      cooperation of epithelial and mesenchymal skin cells in basement membrane
      formation. This interaction is supposedly mediated via diffusible factors. Our
      findings further extend the scope of epithelial-mesenchymal interactions
      stressing that both cell compartments are essential to constitute a tissue
      specific extracellular matrix structure.

PMID- 9521859
TI  - Mechanism of UV-induced apoptosis in human leukemia cells: roles of Ca2+/Mg(2+)
      dependent endonuclease, caspase-3, and stress-activated protein kinases.
AB  - Ultraviolet light (UV) induced rapid apoptosis of U937 leukemia cells, concurrent
      with DNA fragmentation and cleavage of poly(ADP-ribose)polymerase (PARP) by
      activated caspase-3. The in vitro reconstitution of intact HeLa S3 nuclei and
      apoptotic U937 cytosolic extract (CE) revealed that (i) Ca2+/Mg(2+)-dependent,
      Zn(2+)-sensitive endonuclease activated in the apoptotic CE induced DNA ladder in
      HeLa nuclei at pH 6.8-7.4, (ii) activated caspase-3 cleaved PARP in HeLa nuclei,
      and (iii) when the apoptotic CE was treated with the caspase-3 inhibitor (1
      microM Ac-DEVD-CHO) or the caspase-1 inhibitor (10 microM Ac-YVAD-CHO), the
      former, but not the latter, caused a 50% inhibition of DNA fragmentation and the
      complete inhibition of PARP cleavage in HeLa nuclei. Similarly, Ac-DEVD-CHO (100
      microM) inhibited apoptosis and DNA ladder by 50% and PARP cleavage completely in
      UV-irradiated U937 cells, but Ac-YVAD-CHO (100 microM) did not. Thus, UV-induced
      apoptosis of U937 cells involves the Ca2+/Mg(2+)-dependent endonuclease pathway
      and the caspase-3-PARP cleavage-Ca2+/Mg(2+)-dependent endonuclease pathway. The
      former pathway produced directly 50% of apoptotic DNA ladder, and the latter
      involved activated caspase-3 and PARP cleavage, followed by formation of the
      remaining 50% DNA ladder by the activated endonuclease. In UV-irradiated B-cell
      lines, further, p53-dependent increase of Bax resulted in a greater caspase-3
      activation compared to its absence. However, UV-induced activation of JNK1 and
      p38 was not affected by the caspase-1 and -3 inhibitors in U937 cells, so that
      caspases-1 and -3 do not function upstream of JNK1 and p38.

PMID- 9521860
TI  - TNF-alpha and 9-cis-retinoic acid synergistically induce ICAM-1 expression:
      evidence for interaction of retinoid receptors with NF-kappa B.
AB  - TNF-alpha and 9-cis-retinoic acid (9-cis-R) synergistically enhance ICAM-1
      protein expression in immortalized human aortic endothelial cells (HAECTs). At a
      TNF-alpha concentration of 0.1 ng/ml, 1 microM 9-cis-R enhanced ICAM-1 protein
      expression 4-fold. Treatment with 1 microM 9-cis-R alone caused no induction of
      ICAM-1 expression. Functional analysis of human ICAM-1 promoter-luciferase
      constructs revealed that the synergism was attributable to transcriptional
      regulation. Expression of a luciferase reporter vector containing a 311-bp
      fragment of the ICAM-1 promoter (-252 to + 59 bp relative to the transcriptional
      start site) was increased 2.9- and 4.9-fold by treatment with 9-cis-R and TNF
      alpha, respectively, while cotreatment with 9-cis-R and TNF-alpha induced
      expression to 19.9-fold. Mutation studies revealed that RARE and NF-kappa B sites
      located respectively at -226 and -188 bp relative to the transcription start site
      are essential for the synergistic control of promoter activity. Mutation of
      either the RARE or the NF-kappa B site eliminated the synergistic enhancement of
      promoter activity. Moreover, mutation of the RARE abrogated promoter activity
      induced by treatment with TNF-alpha alone and mutation of the NF-kappa B site
      eliminated promoter activity induced by treatment with 9-cis-R alone. We conclude
      that retinoid receptors and NF-kappa B act in concert at the promoter level to
      facilitate ICAM-1 expression in endothelial cells.

PMID- 9521861
TI  - MSJ-1, a new member of the DNAJ family of proteins, is a male germ cell-specific
      gene product.
AB  - A cDNA encoding for a new member of the DnaJ protein family has been isolated by
      screening a mouse spermatogenic cell expression library. The full-length cDNA
      obtained by extension of the original clone with RT-PCR has been characterized
      with respect to its DNA sequence organization and expression. The predicted open
      reading frame encodes a protein of 242 amino acid residues whose sequence is
      similar to that of bacterial DnaJ proteins in the amino-terminal portion since it
      contains the highly conserved J domain which is present in all DnaJ-like proteins
      and is considered to have a critical role in DnaJ protein-protein interactions.
      In contrast, the middle and carboxyl-terminal regions of the protein are not
      similar to any other DnaJ proteins, with the exception of the human neuronal HSJ
      1 with which displays a 48% identity in a 175-amino-acid overlap. Analysis of
      RNAs from a wide spectrum of mouse somatic tissues, including the brain, and from
      ovary and testis reveals that the gene is specifically expressed in testis only.
      Developmental Northern blot analysis of testis RNA from mice of different ages
      and in situ hybridization on juvenile and adult testis sections demonstrate that
      the mRNA is first transcribed in spermatids. A similar pattern of expression is
      exhibited also in rat testis. Based upon all these observations, we have named
      this novel mouse gene, MSJ-1, for mouse sperm cell-specific DNAJ first homolog.

PMID- 9521862
TI  - Alterations in membrane lipid dynamics of leukemic cells undergoing growth arrest
      and differentiation: dependency on the inducing agent.
AB  - The effect of various differentiation inducers on membrane cell dynamics was
      studied using HL-60 and K562 leukemic cell lines. Membrane lipid dynamics was
      measured by the steady-state fluorescence polarization (P) method utilizing
      either 1,6-diphenyl-1,3,5-hexatriene (DPH) or the trimethyl ammonium derivative
      of DPH (TMA-DPH), which ascertains anchorage of the label to the membrane-water
      lipid interface. Decrease in membrane microfluidity was observed in HL-60 cells
      undergoing differentiation into macrophages by 1,25-dihydroxyvitamin D3 and by
      K562 cells induced to differentiate by DMSO. Sodium butyrate caused an increase
      in membrane fluidity in K562 cells undergoing differentiation into erythroid-like
      cells while in HL-60 cells a dual effect was observed. At 0.4 mM concentration,
      in which the cells were induced to differentiate along the monocyte pathway, a
      decrease in membrane fluidity was observed, while at 1 mM concentration an
      increase in membrane fluidity occurred. Interferon-gamma (IFN-gamma) induced an
      increase in membrane fluidity in both cell lines. Using HL-60 cells fluorescently
      labeled by TMA-DPH, similar results indicating fluidization of the membrane
      following IFN-gamma treatment were obtained. Advanced fluorescence lifetime
      measurements, evaluated either by phase modulation spectrofluorometry or by
      single photon correlation fluorometry confirmed that the decrease in fluorescence
      polarization by IFN-gamma resulted from membrane fluidization and not from
      elongation of the probe's excited state lifetime. It is suggested that the
      inducer mode of action, and not the differentiation route, determine the outcome
      of changes in membrane microviscosity.

PMID- 9521863
TI  - Synchronization of cultured vascular smooth muscle cells following reversal of
      quiescence induced by treatment with the antioxidant N-acetylcysteine.
AB  - Smooth muscle cell (SMC) proliferation plays an important role in the
      pathogenesis of vascular diseases such as atherosclerosis and postangioplasty
      restenosis. Recently we demonstrated the thiol antioxidant N-acetylcysteine (NAC)
      inhibits constitutive NF-kappa B/Rel activity and growth of vascular SMCs. Here
      we show that treatment of human and bovine aortic SMC with the thiol antioxidant
      NAC causes cells to exit the cell cycle and remain quiescent as determined by a
      greatly reduced incorporation of [3H]thymidine and G0/G1 DNA content. Removal of
      NAC from the culture medium stimulates SMCs to synchronously reenter the cell
      cycle as judged by induction of cyclin D1 and B-myb gene expression during mid
      and late G1 phase, respectively, and induction of histone gene expression and
      [3H]thymidine incorporation during S phase. The time course of cyclin D1, B-myb,
      and histone gene expression after NAC removal was similar to that of serum
      deprived cells induced to resume cell cycle progression by the addition of fetal
      bovine serum to the culture medium. Taken together, these results indicate that
      NAC treatment causes SMCs to enter a reversible G0 quiescent, growth-arrested
      state. Thus, NAC provides an important new method for synchronizing SMCs in
      culture.

PMID- 9521864
TI  - Identification of glucocorticoid receptor domains necessary for transcriptional
      activation of the mouse mammary tumor virus promoter integrated in the genome.
AB  - It has previously been determined that the mouse mammary tumor virus (MMTV)
      promoter when integrated in the genome assumes a defined chromatin structure
      which is disrupted upon addition of glucocorticoids. In contrast, a transiently
      introduced MMTV promoter has a random nucleoprotein structure. To reveal
      glucocorticoid receptor (GR) domains necessary for transcriptional activation of
      the MMTV promoter we compared the effects of mutations of the GR on
      transcriptional activation of the stably integrated versus transiently introduced
      MMTV promoter. For this purpose we generated a GR-negative cell line which has an
      MMTV promoter/reporter construct integrated in the genome and studied the
      transcriptional activation of this construct by different GR mutants introduced
      into the cells. Transcriptional activation of the integrated and transiently
      introduced promoter was achieved by the wild-type GR or a chimeric receptor in
      which the MR hormone-binding domain (HBD) replaced the GR HBD. In contrast, we
      found that deletion of the HBD of the GR or replacement of this region with the
      equivalent domain of the estrogen receptor produced receptors that were unable to
      activate the MMTV promoter integrated in the genome although these receptors
      efficiently activated the transiently introduced MMTV promoter. The HBD was not
      the sole determinant of MMTV transcriptional activation when integrated in the
      genome. Chimeric receptors which harbored the MR amino terminal domain or the
      wild-type MR were also unable to activate the integrated MMTV promoter. Taken
      together, these data indicate a rigid requirement for sequences in both the GR
      amino and the carboxy terminal domains for transcriptional activation of a
      hormone response element in the defined chromatin context of the MMTV promoter.

PMID- 9521866
TI  - Localization of a cell adhesion site on collagen XIV (undulin).
AB  - Cell adhesion to collagen XIV is implied to be mediated by proteoglycans as
      cellular receptors (T. Ehnis et al., 1996, Exp. Cell Res. 229, 388-397). In order
      to define the cell binding region(s), fusion proteins expressed in Escherichia
      coli and covering the large noncollagenous domain NC3 of collagen XIV were used
      as substrates for the adhesion of skin fibroblasts. A prominent cell binding site
      could be localized in the N-terminal fibronectin type III repeat of collagen XIV
      and its immediate C-terminal extension. Since this region also mediates the
      binding of the small chondroitin/dermatan sulfate proteoglycan decorin (T. Ehnis
      et al., 1997, J. Biol. Chem. 272, 20414-20419), our finding could provide the
      molecular basis for the observation that decorin serves as inhibitor and
      potential modulator of cellular interactions with collagen XIV.

PMID- 9521865
TI  - Role of the bullous pemphigoid antigen 180 (BP180) in the assembly of
      hemidesmosomes and cell adhesion--reexpression of BP180 in generalized atrophic
      benign epidermolysis bullosa keratinocytes.
AB  - Bullous pemphigoid antigen 180 (BP180) is a transmembrane component of
      hemidesmosomes (HD), cell-substrate attachment complexes in stratified and
      complex epithelia. To determine the role of BP180 in the assembly of HD and cell
      adhesion, using SV40 virions we have immortalized BP180-deficient keratinocytes
      derived from a patient with the inherited skin blistering disorder generalized
      atrophic benign epidermolysis bullosa (GABEB). The GABEB keratinocytes form HD
      like structures, which contain alpha 6 beta 4 integrin and HD1/plectin, but not
      the bullous pemphigoid antigen 230 (BP230). The expression of integrin subunits
      by GABEB keratinocytes was comparable to that of an immortalized normal human
      keratinocyte cell line (NHK), except for alpha 6 and beta 4, which were less
      strongly expressed in GABEB cells. In short-term adhesion assays, both GABEB
      keratinocytes and NHK bound strongly and to a similar extent to laminin-1,
      laminin-5, fibronectin, and type IV and V collagens, which suggests that BP180 is
      not involved in promoting the initial adhesion to these ligands. Transfection of
      GABEB keratinocytes with cDNAs for wild-type or a mutant of BP180 lacking the
      collagenous extracellular domain resulted in the expression of recombinant BP180
      proteins that were correctly polarized at the basal cell surface together with
      alpha 6 beta 4. In addition, restored synthesis of BP180 affected the subcellular
      localization of BP230, which was no longer diffusely distributed in the
      cytoplasm, but was found in HD-like structures. In contrast, a BP180 mutant with
      a 36-amino-acid deletion from the amino terminus of the cytoplasmic domain failed
      to localize to HD-like structures. These results demonstrate that a region within
      the cytoplasmic domain of BP180 is essential for its localization into HD and
      that BP180 may play a critical role in coordinating the subcellular distribution
      of BP230.

PMID- 9521867
TI  - Expression of genes (CAPN3, SGCA, SGCB, and TTN) involved in progressive muscular
      dystrophies during early human development.
AB  - The developmental expression pattern of four human genes, three of which are
      involved in progressive muscular dystrophies, was investigated. The rationale for
      these experiments is that these patterns might provide useful information on the
      pathophysiology underlying these myopathies. Despite the presence of overlapping
      clinical signs, the spatiotemporal expression profiles of the corresponding genes
      differed widely. Transcripts of alpha-sarcoglycan (SGCA) were visible as soon as
      myotomes were formed, and constitute, together with titin transcripts, precocious
      muscular system landmarks. beta-sarcoglycan (SGCB) was initially transcribed in a
      ubiquitous manner, and, toward the second part of the embryonic period, became
      specific to striated muscle, heart, and the central nervous system. Whereas titin
      (TTN) transcription and translation seem to be coupled, for the sarcoglycans,
      translation seemed restricted to skeletal muscle. Calpain3 (CAPN3) RNA was found
      in only skeletal muscles during the fetal period. It was, however, present
      earlier in the whole heart, where it selectively disappeared. Finally, evidence
      for differentially spliced calpain3 variants in smooth muscles was also seen. The
      expression profiles of these genes is suggestive of their having a role during
      myogenesis, knowledge of which could be pertinent to the understanding of the
      pathophysiology of the associated diseases.

PMID- 9521868
TI  - Cloning and expression of an immunoglobulin superfamily gene (IGSF1) in Xq25.
AB  - We have isolated a novel full-length cDNA for a gene (IGSF1) located in distal
      Xq25. This transcript is highly expressed in adult testis and fetal liver but is
      undetectable in adult liver. A smaller alternate form is highly expressed in
      adult heart. The gene encodes a protein of 1327 amino acids with several
      recognizable functional domains. The protein has a putative signal peptide and
      transmembrane region, 15 potential sites for N-linked glycosylation, and 12 C2
      type immunoglobulin (Ig)-like domains. All of the Ig-like domains contain the two
      conserved cysteine residues that form intradomain disulfide bonds typical of this
      superfamily. These features are consistent with a possible role for this molecule
      in cell surface recognition or cell-cell interaction.

PMID- 9521869
TI  - A mouse single-copy gene, Gtf2i, the homolog of human GTF2I, that is duplicated
      in the Williams-Beuren syndrome deletion region.
AB  - We have cloned and characterized Gtf2i, the mouse homolog of human GTF2I (general
      transcription factor II-I), which encodes BAP-135, a target for Bruton's tyrosine
      kinase. GTF2I represents the telomeric and functional copy of a duplicated gene
      flanking the 2-Mb Williams-Beuren syndrome (WBS) common deletion at 7q11.23.
      GTF2I is deleted in WBS, while a truncated centromeric pseudogene (GTF2IP1) is
      not deleted. In mouse, there appears to be only a single locus, Gtf2i, which we
      mapped to mouse chromosome 5 in a region of conserved mouse-human synteny. Gtf2i
      is 87.7% identical to GTF2I at the nucleotide and 97% at the amino acid level and
      generates several alternatively spliced transcripts. The gene is widely expressed
      in adult tissues and equally in all areas of the brain. Gtf2i transcript is
      detectable in ES cells by RT-PCR and on Northern blots of tissues from 7-dpc
      embryos. A ubiquitous expression pattern is seen by Northern and tissue in situ
      hybridization studies of 14-dpc embryos.

PMID- 9521870
TI  - Homozygosity and physical mapping of the autosomal recessive retinitis pigmentosa
      locus (RP14) on chromosome 6p21.3.
AB  - Retinitis pigmentosa (RP) is a heterogeneous genetic disorder with autosomal
      dominant, autosomal recessive, and X-linked forms. We previously mapped an
      additional arRP locus to chromosome 6p21 (RP14) in a single extended kinship from
      the Dominican Republic. Aided by a second linked RP pedigree from the same region
      of the Dominican Republic, we have refined the disease locus to a 2-cM region
      that is homozygous-by-descent in both pedigrees. A complete YAC, and a partial
      BAC, contig of the RP14 locus was constructed between the markers D6S1560 and
      D6S291, encompassing approximately 2.1 Mb. The contig contains 12 YACs and 31
      BACs and is characterized by 45 markers including 8 microsatellite markers, 6
      gene-derived sequences/ESTs obtained from the databases, and 28 new STSs and 4
      new ESTs obtained by BLAST search using DNA sequence from the ends of the BAC and
      YAC inserts. With a STS density of approximately 1 every 20 kilobases, this
      contig significantly enhances available maps of the region.

PMID- 9521871
TI  - Cloning and characterization of a novel gene (TM7SF1) encoding a putative seven
      pass transmembrane protein that is upregulated during kidney development.
AB  - We have used the cDNA differential display of mRNA technique to isolate genes
      differentially regulated during kidney development. Here we report the
      identification of a novel gene, TM7SF1, which is upregulated in the course of
      kidney development. The full-length cDNA of TM7SF1 is about 2.4 kb and contains
      an open reading frame of 1197 nucleotides. The predicted secondary structure of
      the corresponding protein displays seven putative helical transmembrane domains,
      a structural feature shared by all members of the G-protein-coupled receptor
      class of transmembrane proteins. Two minor alternatively spliced versions of
      approximately 2.3 and approximately 2.2 kb could be detected, one of which
      contains a nearly identical open reading frame with a truncated carboxy-terminus
      of the deduced protein. The second alternatively spliced version harbors a
      completely shifted open reading frame with a potential new ATG start codon. By
      the use of single-chromosome hybrid cells and fluorescence in situ hybridization
      experiments, TM7SF1 could be localized to chromosome 1q42-q43. Human multiple
      tissue Northern blot analysis revealed TM7SF1 transcripts in human kidney, heart,
      brain, and placenta tissue. Studies on Wilms tumor samples showed variable TM7SF1
      expression, ranging from nearly undetectable levels to an abundant level of
      expression comparable to that of adult kidney tissue.

PMID- 9521872
TI  - Molecular properties and chromosomal location of cadherin-8.
AB  - Cloning of rat cadherin-8 cDNA demonstrated two types of cDNAs. The overall
      structure of the protein defined by one type of the cDNA is essentially the same
      as that of classic cadherins, whereas the protein defined by the other type of
      cDNA ends near the N-terminus of the fifth repeat of the extracellular domain
      (EC5) and contains a short unique sequence at the C-terminus. The same truncated
      type of cDNA was also obtained from a human cDNA library. In Northern blot
      analysis of rat brain mRNA, a probe for EC5 detected multiple bands of about 3.5
      4.3 knt, whereas a probe for the alternative form hybridized with a band of about
      3.5 knt. Western blot experiments showed that an antibody against the
      extracellular domain of rat cadherin-8 stained a band of about 95 kDa and a faint
      band of about 130 kDa in rat brain extract. These results suggest that cadherin-8
      is expressed in two forms, a complete form and a truncated form without a
      transmembrane domain or cytoplasmic domain, in brain. The complete form of
      cadherin-8 expressed in L cells was about 130 kDa in molecular mass and was
      located at the cell periphery, mainly at the cell-cell contact sites. However, we
      failed to express the truncated form in L cells. The transfectants of the
      complete form showed weak cell adhesion activity. The complete form of cadherin-8
      was sensitive to trypsin digestion, and Ca2+ did not protect cadherin-8 from
      digestion, in contrast to the classic cadherins. The complete form of cadherin-8
      coprecipitated with beta-catenin, but did not immunoprecipitate well with alpha
      catenin or gamma-catenin. Cadherin-8, as well as cadherin-11, was mapped to a
      specific region of chromosome 8 that also includes cadherins-1, -3, and -5.

PMID- 9521874
TI  - Genomic organization of the 70-kDa peroxisomal membrane protein gene (PXMP1).
AB  - The 70-kDa peroxisomal membrane protein (PMP70) is a member of a family of half
      ATP-binding cassette (ABC) transporter proteins located in the human peroxisomal
      membrane. Other members include the PMP70-related peroxisomal membrane protein,
      the adrenoleukodystrophy protein (ALDP), and the adrenoleukodystrophy-related
      protein. The functions of ABC transporters in the peroxisomal membrane are poorly
      understood. Evidence from yeast and human mutants suggests that they are involved
      in the peroxisomal import of fatty acids and/or fatty acyl-CoAs into the
      organelle. We report the cloning and characterization of the human PMP70
      structural gene (gene symbol: PXMP1) localized on human chromosome 1p21-p22.
      PXMP1 is approximately 65 kb in length, contains 23 exons, and is quite different
      in structure from the gene (ALD) that encodes the related protein, ALDP. We also
      analyzed the 5' flanking region of the human PXMP1 gene and the corresponding
      region of murine Pxmp-1. Both promoters have features of housekeeping genes,
      including a high GC content and multiple consensus Sp1 binding sequences. In more
      than 3 kb of Pxmp-1 5' flanking sequence we did not identify a consensus
      peroxisomal proliferator responsive element.

PMID- 9521873
TI  - Structure and genomic organization of the human AUF1 gene: alternative pre-mRNA
      splicing generates four protein isoforms.
AB  - The steady-state levels of many mRNAs are determined in part by their turnover
      rates. Turnover rates, in turn, are usually controlled by proteins that bind cis
      acting sequence elements in mRNAs. One class of cis-acting instability
      determinants is composed of A + U-rich elements present in the 3'-UTRs of many
      labile mRNAs. Many A + U-rich elements are bound by the AUF1 family of RNA
      binding proteins, which may target these mRNAs for rapid decay. cDNA cloning and
      immunoblot analyses suggest that the AUF1 family consists of at least four
      isoforms. Previous genomic cloning combined with FISH and Southern analyses of a
      panel of monochromosomal mouse/human or hamster/human somatic cell hybrids
      localized two AUF1 loci to human 4q21.1-q21.2 and Xq12 (B. Wagner et al., 1996,
      Genomics 34: 219-222). In the present study AUF1 gene organization was examined.
      The results suggest that the four known AUF1 isoforms are generated by
      alternative pre-mRNA splicing of a transcript encoded by the chromosome 4 locus.
      Functionally, this creates isoforms with different RNA-binding affinities and
      specificities. Thus, alternative pre-mRNA splicing may serve to create functional
      versatility within the AUF1 family of proteins.

PMID- 9521875
TI  - The mouse transketolase (TKT) gene: cloning, characterization, and functional
      promoter analysis.
AB  - The transketolase (TKT) gene is expressed 30-50 times more highly in the mature
      mouse cornea than in other tissues. Here, we have cloned and characterized the 30
      to 40-kb single-copy mouse TKT gene. Sequence analysis supports the suggestion
      that present-day TKT and TKT-like genes arose from the duplication of a single
      common ancestral gene. A 6-bp polymorphism is present between different mouse
      strains in the noncoding region of exon 2. 5' RACE and primer extension analyses
      indicated that two regions separated by 630 bp are used as transcription
      initiation sites; both mRNAs appear to use a common initiator ATG codon. The
      minor distal transcription initiation site, preceded by a TATA sequence, is
      utilized in liver and is followed by an untranslated exon (exon 1). The major
      proximal transcription initiation site lies within intron 1, is used in cornea
      and liver, lacks a TATA sequence, is GC rich, and initiates at multiple sites
      within a 10-bp span, resembling the promoters of other housekeeping genes. In
      transfected cornea and lens cell lines, the -49/+90 fragment fused to the CAT
      gene acted as a minimal promoter, with higher activity noted for the -510/+91
      fragment. TKT mRNA levels increased sixfold in the mouse cornea in vivo within 1
      2 days of eye opening and were elevated in a lens cell line exposed to H2O2 or
      the glutathione-specific oxidizing agent diamide and in whole newborn mouse eyes
      incubated in the presence of light, consistent with multiple consensus stress
      inducible control sequences in the TKT promoter regions. Taken together, these
      observations suggest that oxidative stress may play a role in the regulation of
      this gene in the cornea.

PMID- 9521876
TI  - Multiple copies of the ALA-D gene are located at the Lv locus in Mus domesticus
      mice.
AB  - Incremental differences in delta-aminolevulinate dehydratase (ALA-D; the second
      enzyme of the heme biosynthetic pathway) activity among inbred mouse strains can
      be attributed to variation in the number of copies of the ALA-D gene. We have
      cloned and characterized the Lv locus from an inbred mouse strain (DBA/2J) that
      has three times the normal ALA-D activity levels. The entire 12-kb ALA-D gene
      plus 16 kb of flanking DNA are found in 28-kb tandemly repeating units. We used
      the derived nucleotide sequence surrounding the internal junction of the repeats
      to survey wild-caught mice and demonstrate that multiple copies of the ALA-D gene
      occur in 7 of 24 worldwide locations of Mus domesticus mice. Data are consistent
      with a model that high lead (Pb) in the environment may be providing a selective
      advantage to mice harboring multiple copies of the ALA-D gene, since the enzyme
      is potently inhibited by lead.

PMID- 9521877
TI  - A high-resolution metric HAPPY map of human chromosome 14.
AB  - We have mapped 1001 novel sequence-tagged sites on human chromosome 14. The mean
      spacing between markers is approximately 90 kb, most markers are mapped with a
      resolution of better than 100 kb, and physical distances are determined. The map
      was produced using HAPPY mapping, a simple and widely applicable in vitro
      approach that is analogous to linkage or to radiation hybrid mapping, but that
      circumvents many of the difficulties and potential artifacts associated with
      these methods. We show also that the map serves as a robust scaffold for building
      physical maps using large-insert clones.

PMID- 9521878
TI  - cDNA cloning, mRNA expression, and chromosomal mapping of human and mouse
      periplakin genes.
AB  - A portion of the intracellular domain of Type XVII collagen, used as a bait in a
      yeast two-hybrid screen of an epidermal keratinocyte cDNA library, identified
      overlapping cDNA clones that showed a high degree of homology to envoplakin and
      other members of the plakin family of intermediate filament connector molecules.
      Subsequent cloning allowed identification of contiguous cDNA sequences with an
      open reading frame of 5268 bp encoding a putative polypeptide of 1756 amino acids
      with a computed molecular mass of 204.7 kDa. Northern analysis using these cDNA
      clones revealed a prominent band of approximately 6.5 kb in keratinocytes, which
      was barely detectable in fibroblasts. Multiple tissue RNA analysis showed that
      this protein is highly expressed in tissues with a prominent component of
      epithelial cells. This novel member of the plakin family was designated
      periplakin. The human gene (PPL) was mapped to the interval between D16S510 and
      D16S509 by radiation hybrid mapping, corresponding to chromosomal band 16p13.
      Murine ESTs having 97.2% amino acid identity to the human sequence were
      identified. Interspecific backcross mapping was used to place the murine
      periplakin gene (Ppl) 0.53 cM distal to marker D16mit32 on the proximal part of
      murine chromosome 16, close to the locus of mahoganoid (md), a mouse hair mutant.
      Mapping of this gene in human and mouse will allow evaluation of periplakin as a
      candidate locus for disorders of epithelial fragility, with or without other
      phenotypes.

PMID- 9521879
TI  - Cloning of the canine beta-glucuronidase cDNA, mutation identification in canine
      MPS VII, and retroviral vector-mediated correction of MPS VII cells.
AB  - Mucopolysaccharidosis type VII (MPS VII) is an inherited disease resulting from
      deficient activity of the lysosomal acid hydrolase beta-glucuronidase (GUSB) and
      has been reported in humans, mice, cats, and dogs. To characterize canine MPS
      VII, we have isolated and sequenced the canine GUSB cDNA from normal and affected
      animals. A single nucleotide substitution was detected in the GUSB cDNA derived
      from MPS VII dogs. This guanosine to adenine base change at nucleotide position
      559 in the canine cDNA sequence causes an arginine to histidine substitution at
      amino acid position 166. Introduction of the G to A substitution at position 559
      in a mammalian expression vector containing the normal canine GUSB cDNA nearly
      eliminated the GUSB enzymatic activity, demonstrating that this mutation is the
      cause of canine MPS VII. A retroviral vector expressing the full-length canine
      beta-glucuronidase cDNA corrected the deficiency in MPS VII cells.

PMID- 9521880
TI  - Isolation and chromosomal mapping of the human homolog of perilipin (PLIN), a rat
      adipose tissue-specific gene, by differential display method.
AB  - Using the differential display technique, we isolated a cDNA clone encoding the
      human homolog of rat perilipin, a unique protein associated with intracellular
      neutral lipid droplets in adipocytes and steroidogenic cells. The full cDNA
      contains an open reading frame of 1566 nucleotides encoding 522 amino acids and
      bears 79% amino acid identity to rat perilipin. Northern blot analysis showed
      that among 20 human adult tissues examined, human perilipin was expressed
      specifically in adipose tissues. We determined the chromosomal location of the
      perilipin gene at 15q26 by means of fluorescence in situ hybridization.

PMID- 9521881
TI  - Physical linkage of the human growth hormone gene cluster and the CD79b (Ig
      beta/B29) gene.
AB  - We have previously characterized a locus control region for the GH1 gene
      consisting of four DNase I hypersensitive sites (HS) located between 14.5 and 32
      kb 5' to the GH1 gene transcription start site. Sequence analysis of the region
      between the GH1 gene and its most proximal HS (HSI) revealed a perfect match to
      the B-lymphocyte-specific CD79b gene. Restriction mapping and hybridization
      analysis of YAC and cosmid clones confirmed the close linkage of the CD79b gene
      to the hGH gene cluster and facilitated the assembly of a 100-kb physical map
      linking the hGH locus, the CD79b gene, and the more distant muscle-specific
      sodium channel alpha-subunit (SCN4A) gene.

PMID- 9521882
TI  - cDNA characterization and chromosome mapping of the human GAS2 gene.
AB  - Murine Gas2 is a microfilament-associated protein whose expression is increased
      at growth arrest in mammalian cells. During apoptosis, Gas2 is specifically
      cleaved at its C-terminus by a still unknown ICE-like protease, and the processed
      protein induces dramatic rearrangements in the cytoskeleton when overexpressed in
      several cell types. Here we report the characterization of a cDNA encoding the
      human homologue of Gas2, showing high conservation with the murine counterpart at
      the protein level. Fluorescence in situ hybridization analysis and radiation
      hybrid mapping localized the GAS2 gene on human chromosome 11p14.3-p15.2, in a
      region homologous to the gas2 region on mouse chromosome 7.

PMID- 9521883
TI  - P450RAI (CYP26A1) maps to human chromosome 10q23-q24 and mouse chromosome 19C2-3.

PMID- 9521884
TI  - Mapping of the human HPRP3 and HPRP4 genes encoding U4/U6-associated splicing
      factors to chromosomes 1q21.1 and 9q31-q33.

PMID- 9521885
TI  - Assignment of the mouse Pde7A gene to the proximal region of chromosome 3 and of
      the human PDE7A gene to chromosome 8q13.

PMID- 9521886
TI  - Alpha adrenoceptors in the rabbit ear thermoregulatory microcirculation.
AB  - The rabbit ear microcirculation was analyzed in a chronic unanesthetized model to
      evaluate alpha adrenergic microvascular control in a thermoregulatory end organ.
      This model allowed direct measurement of microcirculatory responses without the
      effects of anesthetics or inflammatory responses induced by acute surgical
      intervention. The ipsilateral facial artery was catheterized for drug injections
      into the experimental ear. Microvascular diameter changes following stimulation
      or blockade of adrenoceptor (AR) subtypes were observed directly through a
      chronic microvascular chamber implanted in the rabbit ear. Vascular alpha1- and
      alpha2-ARs appear to be distributed differently across the arterioles and AVAs of
      the rabbit ear. Both alpha1- and alpha2-ARs appear to contribute to
      vasoconstriction of AVAs in the conscious rabbit ear. In contrast, alpha1-AR's
      (vs alpha2-ARs) appear to predominate in adrenergically mediated sympathetic
      vasoconstriction of arterioles.

PMID- 9521887
TI  - In vitro side-view imaging technique and analysis of human T-leukemic cell
      adhesion to ICAM-1 in shear flow.
AB  - The objective of the present study is to apply a novel side-view imaging
      technique to investigate T-leukemic Jurkat cell adhesion to a surface-immobilized
      ICAM-1 in shear flow, a ligand for leukocyte LFA-1. Images have revealed that
      Jurkat cell adhesion on ICAM-1 under flow conditions in vitro is quasistatic. The
      cell-substrate contact length steadily increased with time during the initial
      cell attachment to the ICAM-1-coated surface and subsequently decreased with time
      as the trailing edge of the cell membrane peeled away from the substrate under
      the influence of fluid shear forces. Changes in flow shear stresses, cell
      deformability, or substrate ligand strength resulted in a significant change in
      the characteristic adhesion binding time and contact length. A 3-D flow field
      with shear stresses acting on an adherent cell was calculated by using finite
      element methods based on cell shapes obtained from the in vitro images. The
      maximum shear stress acting on an actual cell body was found to be 3-5 times
      greater than the upstream inlet wall shear stress and was influenced by the
      extent of cell deformation within the flow channel. Therefore, the application of
      such a side-view imaging technique has provided a practical assay to study the
      mechanics of cell-surface adhesion in 3-D. The elongation of cells in shear flow
      tempers hydrodynamic shear forces on the cell, which affects the transients in
      cell-surface adhesion.

PMID- 9521888
TI  - Prazosin administration enhances proliferation of arteriolar adventitial
      fibroblasts.
AB  - Chronic vasodilation stimulates the formation of new arterioles in skeletal
      muscle, a process that requires the differentiation of mesenchymally derived
      precursor cells on the abluminal surface of capillaries. Fibroblast proliferation
      and migration to the arterializing capillary likely precede this differentiation
      process. In the current study, we investigated the effects of chronic
      vasodilation with the alpha1 adrenergic blocker prazosin, a treatment that
      produces enhanced terminal arteriolar development, on the proliferation of
      fibroblasts present in the adventitia of transverse arterioles. Dual
      immunofluorescence labeling for the smooth muscle contractile protein SM-myosin
      heavy chain (MHC) and for bromodeoxyuridine (BRDU) uptake revealed that prazosin
      treatment for 4 days stimulated a threefold increase in the density of
      proliferating fibroblasts surrounding transverse arteriolar trees. This increase
      was primarily due to an eightfold increase in the density of S-phase fibroblasts
      surrounding <8 micron m diameter terminal arterioles and a 280% increase in the
      density of S-phase fibroblasts surrounding 8- to 12-micron m terminal arterioles.
      Alcian blue counterstaining indicated that no proliferating cells were mast
      cells. An in vitro study demonstrated that prazosin, at concentrations of 0.5 and
      0.05 mg/liter, has no direct effect on fibroblast proliferation. It is concluded
      that chronic vasodilation with prazosin, a treatment that elicits elevated levels
      of hemodynamic stress, stimulates the proliferation of adventitial fibroblasts,
      particularly at the terminal endings of transverse arteriolar trees.

PMID- 9521889
TI  - Indocyanine green: physicochemical factors affecting its fluorescence in vivo.
AB  - This study reinvestigates the spectral properties of ICG (Indocyanine green) in
      vivo, the role of quenching, and the possibility of an interaction of ICG with
      blood components and/or vessel walls. ICG quenching as a function of
      concentration was studied by spectrophotometry on whole blood samples from golden
      hamsters. Fluorescence ICG characteristics were evaluated by front-face
      fluorometry. In vivo, fluorescence measurements were performed on the femoral
      artery of golden hamsters. In vitro, on whole blood samples, fluorescence
      intensity is modified by ICG quenching as concentration increases above 80
      microgram/ml. The maximum fluorescence peak is not affected and remains centered
      at 832 nm. The in vivo measurements display a similar fluorescence intensity
      shape, which is affected only by ICG concentrations. However, the maximum
      fluorescence emission peak is modified significantly with time. Between 0 and 120
      min, four phases can be distinguished in which a wavelength shift from 826 to 835
      nm is observed. The wavelength shift with change in fluorescence intensity
      observed in vivo could be due to a localization of ICG molecules in sites more
      hydrophobic than serum proteins. It is possible to hypothesize the presence of an
      endothelium-bound form with a specific fluorescence spectrum. The amphiphilic
      properties of ICG are consistent with fixation of some ICG molecules on sites
      other than plasmatic proteins after injection. The process of fixation of ICG
      molecules on surface components or within the vascular endothelium could be due
      to a change in the microenvironment of some ICG molecules.

PMID- 9521890
TI  - Microvascular hematocrit and permeability-surface area product in contracting
      canine skeletal muscle in situ.
AB  - The dynamics of the microvasculature of the blood-perfused canine gastrocnemius
      plantaris muscle in situ at rest and during contraction were determined using
      multiple-indicator dilution analysis. Permeability-surface area product (PS) was
      estimated using a bolus indicator dilution of 86Rb, with 125I-albumin serving as
      the reference tracer, while microvascular hematocrit (Hmv) was estimated using
      the relationship between plasma (125I-albumin) and erythrocyte (51Cr) tracer
      washout curves. The muscle was stimulated to contract, under self-perfusion, for
      3-min periods with either isometric twitch (1.5, 3, or 5 Hz; 4 ms) or tetanic
      (20, 40, or 60 trains/min, 200 ms, 100 Hz) contractions, separated by 25 min of
      rest, randomized to prevent ordering effects. At all stimulation frequencies, Hmv
      increased significantly from rest value of 36.5 +/- 1.6% to 3 min of either
      isometric twitch or tetanic contractions. PS rose significantly from 0.08 +/-
      0.002 ml/g min at rest to a maximum of 0. 40 +/- 0.01 ml/g min at 60 isometric
      tetanic contractions per minute and 0.38 +/- 0.01 at 5 Hz. Changes in PS appeared
      related to stimulation frequency in both twitch and tetanic contractions. The
      change in Hmv with muscle contraction appeared to depend on contraction frequency
      during twitch contractions only, but was independent of stimulus frequency during
      tetanic contractions.

PMID- 9521891
TI  - In vivo measurement of morphometric and hemodynamic changes in the
      microcirculation during angiogenesis under chronic alpha1-adrenergic blocker
      treatment.
AB  - The effect of chronic administration of the alpha 1 blocker prazosin on
      microvascular angiogenesis was studied in rabbit ear chamber to investigate the
      role of concomitant increase in flow-oriented wall shear stress in vascular
      remodeling during angiogenesis. Rabbits were treated with prazosin hydrochloride
      (50 mg/liter in water) orally after ear chambers were installed. The
      microcirculation in the chamber was observed and recorded from 4 to 23
      postoperative day (POD) by an intravital videomicroscope. The total vascular area
      (TA) were quantified as a morphometric parameter. Changes in wall shear stress in
      venules (20-40 micron ID) were calculated from flow velocity, vessel diameter,
      and in vivo blood viscosity. TA was significantly increased in the prazosin
      treated animals. The levels of shear stress, which was increased 1.43 times by
      prazosin on 9 POD, gradually decreased toward the control level on 13 POD and
      they almost coincided on 21 POD. These findings experimentally provided
      supporting evidence that shear stress is probably involved in the adaptive
      response as one of mechanical factors regulating vascular remodeling during
      angiogenesis.

PMID- 9521892
TI  - Comparison of VEGF delivery techniques on collateral-dependent microvascular
      reactivity.

PMID- 9521893
TI  - Three-dimensional investigation of vascular nets by fluorochrome-labeled
      angiography.

PMID- 9521894
TI  - Striated muscle microvascular hematocrit: the increase from rest to contraction.

PMID- 9521895
TI  - vasa is required for GURKEN accumulation in the oocyte, and is involved in oocyte
      differentiation and germline cyst development.
AB  - The Drosophila gene vasa is required for pole plasm assembly and function, and
      also for completion of oogenesis. To investigate the role of vasa in oocyte
      development, we generated a new null mutation of vasa, which deletes the entire
      coding region. Analysis of vasa-null ovaries revealed that the gene is involved
      in the growth of germline cysts. In vasa-null ovaries, germaria are atrophied,
      and contain far fewer developing cysts than do wild-type germaria; a phenotype
      similar to, but less severe than, that of a null nanos allele. The null mutant
      also revealed roles for vasa in oocyte differentiation, anterior-posterior egg
      chamber patterning, and dorsal-ventral follicle patterning, in addition to its
      better-characterized functions in posterior embryonic patterning and pole cell
      specification. The anterior-posterior and dorsal-ventral patterning phenotypes
      resemble those observed in gurken mutants. vasa-null oocytes fail to efficiently
      accumulate many localized RNAs, such as Bicaudal-D, orb, oskar, and nanos, but
      still accumulate gurken RNA. However, GRK accumulation in the oocyte is severely
      reduced in the absence of vasa function, suggesting a function for VASA in
      activating gurken translation in wild-type ovaries.

PMID- 9521896
TI  - Homeotic gene action in embryonic brain development of Drosophila.
AB  - Studies in vertebrates show that homeotic genes are involved in axial patterning
      and in specifying segmental identity of the embryonic hindbrain and spinal cord.
      To gain further insights into homeotic gene action during CNS development, we
      here characterize the role of the homeotic genes in embryonic brain development
      of Drosophila. We first use neuroanatomical techniques to map the entire
      anteroposterior order of homeotic gene expression in the Drosophila CNS, and
      demonstrate that this order is virtually identical in the CNS of Drosophila and
      mammals. We then carry out a genetic analysis of the labial gene in embryonic
      brain development. Our analysis shows that loss-of-function mutation and
      ubiquitous overexpression of labial results in ectopic expression of neighboring
      regulatory genes. Furthermore, this analysis demonstrates that mutational
      inactivation of labial results in regionalized axonal patterning defects which
      are due to both cell-autonomous and cell-nonautonomous effects. Thus, in the
      absence of labial, mutant cells are generated and positioned correctly in the
      brain, but these cells do not extend axons. Additionally, extending axons of
      neighboring wild-type neurons stop at the mutant domains or project ectopically,
      and defective commissural and longitudinal pathways result. Immunocytochemical
      analysis demonstrates that cells in the mutant domains do not express neuronal
      markers, indicating a complete lack of neuronal identity. An alternative glial
      identity is not adopted by these mutant cells. Comparable effects are seen in
      Deformed mutants but not in other homeotic gene mutants. Our findings demonstrate
      that the action of the homeotic genes labial and Deformed are required for
      neuronal differentiation in the developing brain of Drosophila.

PMID- 9521897
TI  - A plasticity window for blood vessel remodelling is defined by pericyte coverage
      of the preformed endothelial network and is regulated by PDGF-B and VEGF.
AB  - Little is known about how the initial endothelial plexus is remodelled into a
      mature and functioning vascular network. Studying postnatal remodelling of the
      retina vasculature, we show that a critical step in vascular maturation, namely
      pericyte recruitment, proceeds by outmigration of cells positive for (alpha)
      smooth muscle actin from arterioles and that coverage of primary and smaller
      branches lags many days behind formation of the endothelial plexus. The transient
      existence of a pericyte-free endothelial plexus coincides temporally and
      spatially with the process of hyperoxia-induced vascular pruning, which is a
      mechanism for fine tuning of vascular density according to available oxygen.
      Acquisition of a pericyte coating marks the end of this plasticity window. To
      substantiate that association with pericytes stabilizes the vasculature,
      endothelial-pericyte associations were disrupted by intraocular injection of PDGF
      BB. Ectopic PDGF-BB caused the detachment of PDGF-beta receptor-positive
      pericytes from newly coated vessels, presumably through interference with
      endogenous cues, but had no effect on mature vessels. Disruption of endothelial
      pericyte associations resulted in excessive regression of vascular loops and
      abnormal remodelling. Conversely, intraocular injection of VEGF accelerated
      pericyte coverage of the preformed endothelial plexus, thereby revealing a novel
      function of this pleiotropic angiogenic growth factor. These findings also
      provide a cellular basis for clinical observations that vascular regression in
      premature neonates subjected to oxygen therapy [i.e. in retinopathy of
      prematurity] drops precipitously upon maturation of retina vessels and a
      mechanistic explanation to our previous findings that VEGF can rescue immature
      vessels from hyperoxia-induced regression.

PMID- 9521898
TI  - Regulation of bHLH-PAS protein subcellular localization during Drosophila
      embryogenesis.
AB  - The Drosophila Single-minded and Tango basic-helix-loop-helix-PAS protein
      heterodimer controls transcription and embryonic development of the CNS midline
      cells, while the Trachealess and Tango heterodimer controls tracheal cell and
      salivary duct transcription and development. Expression of both single-minded and
      trachealess is highly restricted to their respective cell lineages, however tango
      is broadly expressed. The developmental control of subcellular localization of
      these proteins is investigated because of their similarity to the mammalian basic
      helix-loop-helix-PAS Aromatic hydrocarbon receptor whose nuclear localization is
      dependent on ligand binding. Confocal imaging of Single-minded and Trachealess
      protein localization indicate that they accumulate in cell nuclei when initially
      synthesized in their respective cell lineages and remain nuclear throughout
      embryogenesis. Ectopic expression experiments show that Single-minded and
      Trachealess are localized to nuclei in cells throughout the ectoderm and
      mesoderm, indicating that nuclear accumulation is not regulated in a cell
      specific fashion and unlikely to be ligand dependent. In contrast, nuclear
      localization of Tango is developmentally regulated; it is localized to the
      cytoplasm in most cells except the CNS midline, salivary duct, and tracheal cells
      where it accumulates in nuclei. Genetic and ectopic expression experiments
      indicate that Tango nuclear localization is dependent on the presence of a basic
      helix-loop-helix-PAS protein such as Single-minded or Trachealess. Conversely,
      Drosophila cell culture experiments show that Single-minded and Trachealess
      nuclear localization is dependent on Tango since they are cytoplasmic in the
      absence of Tango. These results suggest a model in which Single-minded and
      Trachealess dimerize with Tango in the cytoplasm of the CNS midline cells and
      trachea, respectively, and the dimeric complex accumulates in nuclei in a ligand
      independent mode and regulates lineage-specific transcription. The lineage
      specific action of Single-minded and Trachealess derives from transcriptional
      activation of their genes in their respective lineages, not from extracellular
      signaling.

PMID- 9521899
TI  - A common mechanism controls the life cycle and architecture of plants.
AB  - The overall aerial architecture of flowering plants depends on a group of
      meristematic cells in the shoot apex. We demonstrate that the Arabidopsis
      TERMINAL FLOWER 1 gene has a unified effect on the rate of progression of the
      shoot apex through different developmental phases. In transgenic Arabidopsis
      plants which ectopically express TERMINAL FLOWER 1, both the vegetative and
      reproductive phases are greatly extended. As a consequence, these plants exhibit
      dramatic changes in their overall morphology, producing an enlarged vegetative
      rosette of leaves, followed by a highly branched inflorescence which eventually
      forms normal flowers. Activity of the floral meristem identity genes LEAFY and
      APETALA 1 is not directly inhibited by TERMINAL FLOWER 1, but their upregulation
      is markedly delayed compared to wild-type controls. These phenotypic and
      molecular effects complement those observed in the tfl1 mutant, where all phases
      are shortened. The results suggest that TERMINAL FLOWER 1 participates in a
      common mechanism underlying major shoot apical phase transitions, rather than
      there being unrelated mechanisms which regulate each specific transition during
      the life cycle.

PMID- 9521900
TI  - CHR3: a Caenorhabditis elegans orphan nuclear hormone receptor required for
      proper epidermal development and molting.
AB  - CHR3 is a Caenorhabditis elegans orphan nuclear hormone receptor highly
      homologous to Drosophila DHR3, an ecdysone-inducible gene product involved in
      metamorphosis. Related vertebrate factors include RORalpha/RZRalpha, RZRbeta and
      RevErb. Gel-shift studies show that CHR3 can bind the DR5-type hormone response
      sequence. CHR3 is a nuclear protein present in all blastomeres during early
      embryogenesis. During morphogenesis, both CHR3 protein and zygotically active
      reporter genes are detectable in epidermal cells and their precursors. Inhibition
      of the gene encoding CHR3 results in several larval defects associated with
      abnormal epidermal cell function, including molting and body size regulation,
      suggesting that CHR3 is an essential epidermal factor required for proper
      postembryonic development.

PMID- 9521901
TI  - Adenovirus-mediated ectopic expression of Msx2 in even-numbered rhombomeres
      induces apoptotic elimination of cranial neural crest cells in ovo.
AB  - Distinct cranial neural crest-derived cell types (a number of neuronal as well as
      non-neuronal cell lineages) are generated at characteristic times and positions
      in the rhombomeres of the hindbrain in developing vertebrate embryos. To examine
      this developmental process, we developed a novel strategy designed to test the
      efficacy of gain-of-function Msx2 expression within rhombomeres in ovo prior to
      the emigration of cranial neural crest cells (CNCC). Previous studies indicate
      that CNCC from odd-numbered rhombomeres (r3 and r5) undergo apoptosis in response
      to exogenous BMP4. We provide evidence that targeted infection in ovo using
      adenovirus containing Msx2 and a reporter molecule indicative of translation can
      induce apoptosis in either even- or odd-numbered rhombomeres. Furthermore,
      infected lacZ-control explants indicated that CNCC emigrated, and that 20% of
      these cells were double positive for crest cell markers HNK-1 and beta-gal. In
      contrast, there were no HNK-1 and Msx2 double positive cells emigrating from Msx2
      infected explants. These results support the hypothesis that apoptotic
      elimination of CNCC can be induced by 'gain-of-function' Msx2 expression in even
      numbered rhombomeres. These inductive interactions involve qualitative,
      quantitative, positional and temporal differences in TGF-beta-related signals,
      Msx2 expression and other transcriptional control.

PMID- 9521902
TI  - prdl-a, a gene marker for hydra apical differentiation related to triploblastic
      paired-like head-specific genes.
AB  - Two homeobox genes, prdl-a and prdl-b, which were isolated from a Hydra vulgaris
      cDNA library, encode paired-like class homeodomains highly related to that of the
      aristaless-related genes. In adult polyps, prdl-b is a marker for synchronously
      dividing nematoblasts while prdl-a displays an expression restricted to the the
      nerve cell lineage of the head region. During budding and apical regeneration, an
      early and transient prdl-a expression was observed in endodermal cells of the
      stump at a time when the head organizer is established. When apical regeneration
      was delayed upon concomittant budding, prdl-a expression was found to be altered
      in the stump. Furthermore, a specific anti-prdl-a protein immunoserum revealed
      that prdl-a was overexpressed in adult polyps of the Chlorohydra viridissima
      multiheaded mutant, with an expression domain extending below the tentacle ring
      towards the body column. Accordingly, prdl-a DNA-binding activity was enhanced in
      nuclear extracts from this mutant. These results suggest that prdl-a responds to
      apical forming signals and might thus be involved in apical specification. When a
      marine hydrozoan (Podocorynae carnea) was used, the anti-prdl-a antibody showed
      cross-reactivity with cells located around the oral region, indicating that prdl
      a function is shared by other cnidaria. The ancestral role for prdl-a-related
      genes in the molecular definition of the head (or oral-surrounding region) is
      discussed.

PMID- 9521904
TI  - Runt determines cell fates in the Drosophila embryonic CNS.
AB  - The segmentation gene, runt, is expressed by a subset of the 30 neuroblasts that
      give rise to each neuromere of the Drosophila embryo. Runt activity in the
      neuroblasts is necessary for expression of even-skipped in the EL neurons. runt
      is therefore a good candidate for a gene specifying neuroblast identities. We
      have ectopically expressed Runt in restricted subsets of neuroblasts and show
      that Runt is sufficient to activate even-skipped expression in the progeny of
      specific neuroblasts. Using the marker Tau-green fluorescent protein to highlight
      the axons, we have found that the extra Even-skipped-expressing neurons project
      axons along the same pathway as the EL neurons. We find that Runt is expressed in
      neuroblast 3-3, supporting an autonomous role for runt during neuroblast
      specification.

PMID- 9521903
TI  - The CArG boxes in the promoter of the Arabidopsis floral organ identity gene
      APETALA3 mediate diverse regulatory effects.
AB  - APETALA3 is a MADS box gene required for normal development of the petals and
      stamens in the Arabidopsis flower. Studies in yeast, mammals and plants
      demonstrate that MADS domain transcription factors bind with high affinity to a
      consensus sequence called the CArG box. The APETALA3 promoter contains three
      close matches to the consensus CArG box sequence. To gain insights into the
      APETALA3 regulatory circuitry, we have analyzed the APETALA3 promoter using
      AP3::uidA(GUS) fusions. 496 base pairs of APETALA3 promoter sequence 5' to the
      transcriptional start directs GUS activity in the same temporal and spatial
      expression pattern as the APETALA3 RNA and protein in wild-type flowers. A
      synthetic promoter consisting of three tandem repeats of a 143 base pair sequence
      directs reporter gene activity exclusively to petals and stamens in the flower.
      We have analyzed the role of the CArG boxes by site-specific mutagenesis and find
      that the three CArG boxes mediate discrete regulatory effects. Mutations in CArG1
      result in a decrease in reporter expression suggesting that CArG1 is the binding
      site for a positively acting factor or factors. Mutations in CArG2 result in a
      decrease in reporter expression in petals, but the expression pattern in stamens
      is unchanged. By contrast, mutations in CArG3 result in an increase in the level
      of reporter gene activity during early floral stages suggesting that CArG3 is the
      binding site for a negatively acting factor.

PMID- 9521905
TI  - Genetic analysis of a Hoxd-12 regulatory element reveals global versus local
      modes of controls in the HoxD complex.
AB  - Vertebrate Hoxd genes are essential determinants of limb morphogenesis. In order
      to understand the genetic control of their complex expression patterns, we have
      used a combined approach involving interspecies sequence alignments in parallel
      with transgenic analyses, followed by in vivo mutagenesis. Here, we report on the
      identification of a regulatory element that is located in the vicinity of the
      Hoxd-12 gene. While this element is well conserved in tetrapods, little sequence
      similarity was scored when compared to the cognate fish DNA. The regulatory
      potential of this region XI (RXI) was first assayed in the context of a Hoxd
      12/lacZ reporter transgene and shown to direct reporter gene expression in
      posterior limb buds. A deletion of this region was generated by targeted
      mutagenesis in ES cells and introduced into mice. Analyses of animals homozygous
      for the HoxDRXI mutant allele revealed the function of this region in controlling
      Hoxd-12 expression in the presumptive posterior zeugopod where it genetically
      interacts with Hoxa-11. Downregulation of Hoxd-12 expression was also detected in
      the trunk suggesting that RXI may mediate a rather general function in the
      activation of Hoxd-12. These results support a model whereby global as well as
      local regulatory influences are necessary to build up the complex expression
      patterns of Hoxd genes during limb development.

PMID- 9521907
TI  - Murine Otx1 and Drosophila otd genes share conserved genetic functions required
      in invertebrate and vertebrate brain development.
AB  - Despite the obvious differences in anatomy between invertebrate and vertebrate
      brains, several genes involved in the development of both brain types belong to
      the same family and share similarities in expression patterns. Drosophila
      orthodenticle (otd) and murine Otx genes exemplify this, both in terms of
      expression patterns and mutant phenotypes. In contrast, sequence comparison of
      OTD and OTX gene products indicates that homology is restricted to the
      homeodomain suggesting that protein divergence outside the homeodomain might
      account for functional differences acquired during brain evolution. In order to
      gain insight into this possibility, we replaced the murine Otx1 gene with a
      Drosophila otd cDNA. Strikingly, epilepsy and corticogenesis defects due to the
      absence of Otx1 were fully rescued in homozygous otd mice. A partial rescue was
      also observed for the impairments of mesencephalon, eye and lachrymal gland. In
      contrast, defects of the inner ear were not improved suggesting a vertebrate Otx1
      specific function involved in morphogenesis of this structure. Furthermore, otd,
      like Otx1, was able to cooperate genetically with Otx2 in brain patterning,
      although with reduced efficiency. These data favour an extended functional
      conservation between Drosophila otd and murine Otx1 genes and support the idea
      that conserved genetic functions required in mammalian brain development evolved
      in a primitive ancestor of both flies and mice.

PMID- 9521906
TI  - The PS2 integrin ligand tiggrin is required for proper muscle function in
      Drosophila.
AB  - Tiggrin is a novel extracellular matrix ligand for the Drosophila PS2 integrins.
      We have used flanking P elements to generate a precise deletion of tiggrin. Most
      flies lacking tiggrin die as larvae or pupae. A few adults do emerge and these
      appear to be relatively normal, displaying only misshapen abdomens and a low
      frequency of wing defects. Examination of larvae shows that muscle connections,
      function and morphology are defective in tiggrin mutants. Muscle contraction
      waves that extend the length of the larvae are much slower in tiggrin mutants.
      Direct examination of bodywall muscles shows defects in muscle attachment sites,
      where tiggrin is specifically localized, and muscles appear thinner. Transgenes
      expressing tiggrin are capable of rescuing tiggrin mutant phenotypes. Transgenes
      expressing a mutant tiggrin, whose Arg-Gly-Asp (RGD) integrin recognition
      sequence has been mutated to Leu-Gly-Ala (LGA) show much reduced, but
      significant, rescuing ability. Cell spreading assays detect no interactions of
      this mutant tiggrin with PS2 integrins. Therefore, while the RGD sequence is
      critical for PS2 interactions and full activity in the whole fly, the mutant
      tiggrin retains some function(s) that are probably mediated by interactions with
      other ECM molecules or cell surface receptors

PMID- 9521908
TI  - Equivalence of the fly orthodenticle gene and the human OTX genes in embryonic
      brain development of Drosophila.
AB  - Members of the orthodenticle gene family are essential for embryonic brain
      development in animals as diverse as insects and mammals. In Drosophila,
      mutational inactivation of the orthodenticle gene results in deletions in
      anterior parts of the embryonic brain and in defects in the ventral nerve cord.
      In the mouse, targeted elimination of the homologous Otx2 or Otx1 genes causes
      defects in forebrain and/or midbrain development. To determine the morphogenetic
      properties and the extent of evolutionary conservation of the orthodenticle gene
      family in embryonic brain development, genetic rescue experiments were carried
      out in Drosophila. Ubiquitous overexpression of the orthodenticle gene rescues
      both the brain defects and the ventral nerve cord defects in orthodenticle mutant
      embryos; morphology and nervous system-specific gene expression are restored. Two
      different time windows exist for the rescue of the brain versus the ventral nerve
      cord. Ubiquitous overexpression of the human OTX1 or OTX2 genes also rescues the
      brain and ventral nerve cord phenotypes in orthodenticle mutant embryos; in the
      brain, the efficiency of morphological rescue is lower than that obtained with
      overexpression of orthodenticle. Overexpression of either orthodenticle or the
      human OTX gene homologs in the wild-type embryo results in ectopic neural
      structures. The rescue of highly complex brain structures in Drosophila by either
      fly or human orthodenticle gene homologs indicates that these genes are
      interchangeable between vertebrates and invertebrates and provides further
      evidence for an evolutionarily conserved role of the orthodenticle gene family in
      brain development.

PMID- 9521910
TI  - Oocyte polarity depends on regulation of gurken by Vasa.
AB  - Vasa, a DEAD box mRNA helicase similar to eIF4A, is involved in pole plasm
      assembly in the Drosophila oocyte and appears to regulate translation of oskar
      and nanos mRNAs. However, several vasa alleles exhibit a wide range of early
      oogenesis phenotypes. Here we report a detailed analysis of Vasa function during
      early oogenesis using novel as well as previously identified hypomorphic vasa
      alleles. We find that vasa is required for the establishment of both anterior
      posterior and dorsal-ventral polarity of the oocyte. The polarity defects of vasa
      mutants appear to be caused by a reduction in the amount of Gurken protein at
      stages of oogenesis critical for the establishment of polarity. Vasa is required
      for translation of gurken mRNA during early oogenesis and for achieving wild-type
      levels of gurken mRNA expression later in oogenesis. A variety of early oogenesis
      phenotypes observed in vasa ovaries, which cannot be attributed to the defect in
      gurken expression, suggest that vasa also affects expression of other mRNAs.

PMID- 9521909
TI  - Discrete spatial and temporal cis-acting elements regulate transcription of the
      Arabidopsis floral homeotic gene APETALA3.
AB  - The APETALA3 floral homeotic gene is required for petal and stamen development in
      Arabidopsis. APETALA3 transcripts are first detected in a meristematic region
      that will give rise to the petal and stamen primordia, and expression is
      maintained in this region during subsequent development of these organs. To
      dissect how the APETALA3 gene is expressed in this spatially and temporally
      restricted domain, various APETALA3 promoter fragments were fused to the uidA
      reporter gene encoding beta-glucuronidase and assayed for the resulting patterns
      of expression in transgenic Arabidopsis plants. Based on these promoter analyses,
      we defined cis-acting elements required for distinct phases of APETALA3
      expression, as well as for petal-specific and stamen-specific expression. By
      crossing the petal-specific construct into different mutant backgrounds, we have
      shown that several floral genes, including APETALA3, PISTILLATA, UNUSUAL FLORAL
      ORGANS, and APETALA1, encode trans-acting factors required for second-whorl
      specific APETALA3 expression. We have also shown that the products of the
      APETALA1, APETALA3, PISTILLATA and AGAMOUS genes bind to several conserved
      sequence motifs within the APETALA3 promoter. We present a model whereby
      spatially and temporally restricted APETALA3 transcription is controlled via
      interactions between proteins binding to different domains of the APETALA3
      promoter.

PMID- 9521911
TI  - crooked legs encodes a family of zinc finger proteins required for leg
      morphogenesis and ecdysone-regulated gene expression during Drosophila
      metamorphosis.
AB  - Drosophila imaginal discs undergo extensive pattern formation during larval
      development, resulting in each cell acquiring a specific adult fate. The final
      manifestation of this pattern into adult structures is dependent on pulses of the
      steroid hormone ecdysone during metamorphosis, which trigger disc eversion,
      elongation and differentiation. We have defined genetic criteria that allow us to
      screen for ecdysone-inducible regulatory genes that are required for this
      transformation from patterned disc to adult structure. We describe here the first
      genetic locus isolated using these criteria: crooked legs (crol). crol mutants
      die during pupal development with defects in adult head eversion and leg
      morphogenesis. The crol gene is induced by ecdysone during the onset of
      metamorphosis and encodes at least three protein isoforms that contain 12-18 C2H2
      zinc fingers. Consistent with this sequence motif, crol mutations have stage
      specific effects on ecdysone-regulated gene expression. The EcR ecdysone
      receptor, and the BR-C, E74 and E75 early regulatory genes, are submaximally
      induced in crol mutants in response to the prepupal ecdysone pulse. These changes
      in gene activity are consistent with the crol lethal phenotypes and provide a
      basis for understanding the molecular mechanisms of crol action. The genetic
      criteria described here provide a new direction for identifying regulators of
      adult tissue development during insect metamorphosis.

PMID- 9521912
TI  - Progressive lineage analysis by cell sorting and culture identifies FLK1+VE
      cadherin+ cells at a diverging point of endothelial and hemopoietic lineages.
AB  - Totipotent murine ES cells have an enormous potential for the study of cell
      specification. Here we demonstrate that ES cells can differentiate to hemopoietic
      cells through the proximal lateral mesoderm, merely upon culturing in type IV
      collagen-coated dishes. Separation of the Flk1+ mesoderm from other cell lineages
      was critical for hemopoietic cell differentiation, whereas formation of the
      embryoid body was not. Since the two-dimensionally spreading cells can be
      monitored easily in real time, this culture system will greatly facilitate the
      study of the mechanisms involved in the cell specification to mesoderm,
      endothelial, and hemopoietic cells. In the culture of ES cells, however, lineages
      and stages of differentiating cells can only be defined by their own
      characteristics. We showed that a combination of monoclonal antibodies against E
      cadherin, Flk1/KDR, PDGF receptor(alpha), VE-cadherin, CD45 and Ter119 was
      sufficient to define most intermediate stages during differentiation of ES cells
      to blood cells. Using this culture system and surface markers, we determined the
      following order for blood cell differentiation: ES cell (E-cadherin+Flk1
      PDGFRalpha-), proximal lateral mesoderm (E-cadherin-Flk1+VE-cadherin-),
      progenitor with hemoangiogenic potential (Flk1+VE-cadherin+CD45-), hemopoietic
      progenitor (CD45+c-Kit+) and mature blood cells (c-Kit-CD45+ or Ter119+), though
      direct differentiation of blood cells from the Flk1+VE-cadherin- stage cannot be
      ruled out. Not only the VE-cadherin+CD45- population generated from ES cells but
      also those directly sorted from the yolk sac of 9.5 dpc embryos have a potential
      to give rise to hemopoietic cells. Progenitors with hemoangiogenic potential were
      identified in both the Flk1+VE-cadherin- and Flk1+VE-cadherin+ populations by the
      single cell deposition experiment. This line of evidence implicates Flk1+VE
      cadherin+ cells as a diverging point of hemopoietic and endothelial cell
      lineages.

PMID- 9521913
TI  - A genetic screen for modifiers of Drosophila decapentaplegic signaling identifies
      mutations in punt, Mothers against dpp and the BMP-7 homologue, 60A.
AB  - decapentaplegic (dpp) is a Transforming Growth Factor beta (TGF-beta)-related
      growth factor that controls multiple developmental processes in Drosophila. To
      identify components involved in dpp signaling, we carried out a genetic screen
      for dominant enhancer mutations of a hypomorphic allele of thick veins (tkv), a
      type I receptor for dpp. We recovered new alleles of tkv, punt, Mothers against
      dpp (Mad) and Medea (Med), all of which are known to mediate dpp signaling. We
      also recovered mutations in the 60A gene which encodes another TGF-beta-related
      factor in Drosophila. DNA sequence analysis established that all three 60A
      alleles were nonsense mutations in the prodomain of the 60A polypeptide. These
      mutations in 60A caused defects in midgut morphogenesis and fat body
      differentiation. We present evidence that when dpp signaling is compromised,
      lowering the level of 60A impairs several dpp-dependent developmental processes
      examined, including the patterning of the visceral mesoderm, the embryonic
      ectoderm and the imaginal discs. These results provide the first in vivo evidence
      for the involvement of 60A in the dpp pathway. We propose that 60A activity is
      required to maintain optimal signaling capacity of the dpp pathway, possibly by
      forming biologically active heterodimers with Dpp proteins.

PMID- 9521914
TI  - Nerve-muscle interactions during flight muscle development in Drosophila.
AB  - During Drosophila pupal metamorphosis, the motoneurons and muscles differentiate
      synchronously, providing an opportunity for extensive intercellular regulation
      during synapse formation. We examined the existence of such interactions by
      developmentally delaying or permanently eliminating synaptic partners during the
      formation of indirect flight muscles. When we experimentally delayed muscle
      development, we found that although adult-specific primary motoneuron branching
      still occurred, the higher order (synaptic) branching was suspended until the
      delayed muscle fibers reached a favourable developmental state. In reciprocal
      experiments we found that denervation caused a decrease in the myoblast pool.
      Furthermore, the formation of certain muscle fibers (dorsoventral muscles) was
      specifically blocked. Exceptions were the adult muscles that use larval muscle
      fibers as myoblast fusion targets (dorsal longitudinal muscles). However, when
      these muscles were experimentally compelled to develop without their larval
      precursors, they showed an absolute dependence on the motoneurons for their
      formation. These data show that the size of the myoblast pool and early events in
      fiber formation depend on the presence of the nerve, and that, conversely,
      peripheral arbor development and synaptogenesis is closely synchronized with the
      developmental state of the muscle.

PMID- 9521916
TI  - Editor's note 

PMID- 9521915
TI  - Wnt and TGFbeta signals subdivide the AbdA Hox domain during Drosophila mesoderm
      patterning.
AB  - Hox genes have large expression domains yet control the formation of fine pattern
      elements at specific locations. We have examined the mechanism underlying
      subdivision of the abdominal-A (abdA) Hox domain in the visceral mesoderm. AbdA
      directs formation of an embryonic midgut constriction at a precise location
      within the broad and uniform abdA expression domain. The constriction divides the
      abdA domain of the midgut into two chambers, the anterior one producing the
      Pointed (Pnt) ETS transcription factors and the posterior one the Odd-paired
      (Opa) zinc finger protein. Transcription of both pnt and opa is activated by abdA
      but the adjacent non-overlapping patterns are not due to mutual opa-pnt
      regulation. Near the anterior limit of the abdA domain, two signals, Dpp (a
      TGFbeta) and Wg (a Wnt), are produced, in adjacent non-overlapping patterns,
      under Hox control in mesoderm cells. The two signals are known to regulate local
      mesodermal cell fates and to signal to the endoderm. We find that, in addition,
      they precisely subdivide the abdA domain: Wg acts upon anterior abdA domain cells
      to activate pnt transcription, while Dpp is essential in the same region to
      prevent abdA from activating opa transcription. pnt activation is required to
      determine the appropriate numbers of mesodermal cells in the third midgut
      chamber.

PMID- 9521918
TI  - Phylogenomics: improving functional predictions for uncharacterized genes by
      evolutionary analysis.

PMID- 9521917
TI  - Base qualities help sequencing software.

PMID- 9521919
TI  - Late-night thoughts on the sequence annotation problem.

PMID- 9521920
TI  - WebWise: guide to the Baylor College of Medicine Human Genome Sequencing Center's
      web site.

PMID- 9521921
TI  - Base-calling of automated sequencer traces using phred. I. Accuracy assessment.
AB  - The availability of massive amounts of DNA sequence information has begun to
      revolutionize the practice of biology. As a result, current large-scale
      sequencing output, while impressive, is not adequate to keep pace with growing
      demand and, in particular, is far short of what will be required to obtain the 3
      billion-base human genome sequence by the target date of 2005. To reach this
      goal, improved automation will be essential, and it is particularly important
      that human involvement in sequence data processing be significantly reduced or
      eliminated. Progress in this respect will require both improved accuracy of the
      data processing software and reliable accuracy measures to reduce the need for
      human involvement in error correction and make human review more efficient. Here,
      we describe one step toward that goal: a base-calling program for automated
      sequencer traces, phred, with improved accuracy. phred appears to be the first
      base-calling program to achieve a lower error rate than the ABI software,
      averaging 40%-50% fewer errors in the data sets examined independent of position
      in read, machine running conditions, or sequencing chemistry.

PMID- 9521922
TI  - Base-calling of automated sequencer traces using phred. II. Error probabilities.
AB  - Elimination of the data processing bottleneck in high-throughput sequencing will
      require both improved accuracy of data processing software and reliable measures
      of that accuracy. We have developed and implemented in our base-calling program
      phred the ability to estimate a probability of error for each base-call, as a
      function of certain parameters computed from the trace data. These error
      probabilities are shown here to be valid (correspond to actual error rates) and
      to have high power to discriminate correct base-calls from incorrect ones, for
      read data collected under several different chemistries and electrophoretic
      conditions. They play a critical role in our assembly program phrap and our
      finishing program consed.

PMID- 9521923
TI  - Consed: a graphical tool for sequence finishing.
AB  - Sequencing of large clones or small genomes is generally done by the shotgun
      approach (Anderson et al. 1982). This has two phases: (1) a shotgun phase in
      which a number of reads are generated from random subclones and assembled into
      contigs, followed by (2) a directed, or finishing phase in which the assembly is
      inspected for correctness and for various kinds of data anomalies (such as
      contaminant reads, unremoved vector sequence, and chimeric or deleted reads),
      additional data are collected to close gaps and resolve low quality regions, and
      editing is performed to correct assembly or base-calling errors. Finishing is
      currently a bottleneck in large-scale sequencing efforts, and throughput gains
      will depend both on reducing the need for human intervention and making it as
      efficient as possible. We have developed a finishing tool, consed, which attempts
      to implement these principles. A distinguishing feature relative to other
      programs is the use of error probabilities from our programs phred and phrap as
      an objective criterion to guide the entire finishing process. More information is
      available at http:// www.genome.washington.edu/consed/consed. html.

PMID- 9521924
TI  - Reconstruction of amino acid biosynthesis pathways from the complete genome
      sequence.
AB  - The complete genome sequence of an organism contains information that has not
      been fully utilized in the current prediction methods of gene functions, which
      are based on piece-by-piece similarity searches of individual genes. We present
      here a method that utilizes a higher level information of molecular pathways to
      reconstruct a complete functional unit from a set of genes. Specifically, a
      genome-by-genome comparison is first made for identifying enzyme genes and
      assigning EC numbers, which is followed by the reconstruction of selected
      portions of the metabolic pathways by use of the reference biochemical knowledge.
      The completeness of the reconstructed pathway is an indicator of the correctness
      of the initial gene function assignment. This feature has become possible because
      of our efforts to computerize the current knowledge of metabolic pathways under
      the KEGG project. We found that the biosynthesis pathways of all 20 amino acids
      were completely reconstructed in Escherichia coli, Haemophilus influenzae, and
      Bacillus subtilis, and probably in Synechocystis and Saccharomyces cerevisiae as
      well, although it was necessary to assume wider substrate specificity for
      aspartate aminotransferases.

PMID- 9521925
TI  - Software for constructing and verifying pedigrees within large genealogies and an
      application to the Old Order Amish of Lancaster County.
AB  - This paper describes PedHunter, a software package that facilitates creation and
      verification of pedigrees within large genealogies. A frequent problem in medical
      genetics is to connect distant relatives with a pedigree. PedHunter uses methods
      from graph theory to solve two versions of the pedigree connection problem for
      genealogies as well as other pedigree analysis problems. The pedigrees are
      produced by PedHunter as files in LINKAGE format ready for linkage analysis.
      PedHunter uses a relational database of genealogy data, with tables in specified
      format, for all calculations. The functionality and utility of PedHunter are
      illustrated by examples using the Amish Genealogy Database (AGDB), which was
      created for the Old Order Amish community of Lancaster County, Pennsylvania.

PMID- 9521926
TI  - Computational advances in maximum likelihood methods for molecular phylogeny.
AB  - We have developed a generalization of Kimura's Markov chain model for base
      substitution at a single nucleotide site. This generalized model incorporates
      more flexible transition rates and consequently allows irreversible as well as
      reversible chains. Because the model embodies just the right amount of symmetry,
      it permits explicit calculation of finite-time transition probabilities and
      equilibrium distributions. The model also meshes well with maximum likelihood
      methods for phylogenetic analysis. Quick calculation of likelihoods and their
      derivatives can be carried out by adapting Baum's forward and backward algorithms
      from the theory of hidden Markov chains. Analysis of HIV sequence data
      illustrates the speed of the algorithms on trees with many contemporary taxa.
      Analysis of some of Lake's data on the origin of the eukaryotic nucleus contrasts
      the reversible and irreversible versions of the model.

PMID- 9521928
TI  - Estimation of errors in "raw" DNA sequences: a validation study.
AB  - As DNA sequencing is performed more and more in a mass-production-like manner,
      efficient quality control measures become increasingly important for process
      control, but so also does the ability to compare different methods and projects.
      One of the fundamental quality measures in sequencing projects is the position
      specific error probability at all bases in each individual sequence. Accurate
      prediction of base-specific error rates from "raw" sequence data would allow
      immediate quality control as well as benchmarking different methods and projects
      while avoiding the inefficiencies and time delays associated with resequencing
      and assessments after "finishing" a sequence. The program PHRED provides base
      specific quality scores that are logarythmically related to error probabilities.
      This study assessed the accuracy of PHRED's error-rate prediction by analyzing
      sequencing projects from six different large-scale sequencing laboratories. All
      projects used four-color fluorescent sequencing, but the sequencing methods used
      varied widely between the different projects. The results indicate that the error
      rate predictions such as those given by PHRED can be highly accurate for a large
      variety of different sequencing methods as well as over a wide range of sequence
      quality.

PMID- 9521927
TI  - GAIA: framework annotation of genomic sequence.
AB  - As increasing amounts of genomic sequence from many organisms become available,
      and as DNA sequences become a primary reagent in biologic investigations, the
      role of annotation as a prospective guide for laboratory experiments will expand
      rapidly. Here we describe a process of high-throughput, reliable annotation,
      called framework annotation, which is designed to provide a foundation for
      initial biologic characterization of previously unexamined sequence. To examine
      this concept in practice, we have constructed Genome Annotation and Information
      Analysis (GAIA), a prototype software architecture that implements several
      elements important for framework annotation. The center of GAIA consists of an
      annotation database and the associated data management subsystem that forms the
      software bus along which other components communicate. The schema for this
      database defines three principal concepts: (1) Entries, consisting of sequence
      and associated historical data; (2) Features, comprising information of biologic
      interest; and (3) Experiments, describing the evidence that supports Features.
      The database permits tracking of annotation results over time, as well as
      assessment of the reliability of particular results. New framework annotation is
      produced by CARTA, a set of autonomous sensors that perform automatic analyses
      and assert results into the annotation database. These results are available via
      a Web-based query interface that uses graphical Java applets as well as text
      based HTML pages to display data at different levels of resolution and permit
      interactive exploration of annotation. We present results for initial application
      of framework annotation to a set of test sequences, demonstrating its
      effectiveness in providing a starting point for biologic investigation, and
      discuss ways in which the current prototype can be improved. The prototype is
      available for public use and comment at http://www.cbil.upenn.edu/gaia.

PMID- 9521929
TI  - Sequence assembly with CAFTOOLS.
AB  - Large-scale genomic sequencing requires a software infrastructure to support and
      integrate applications that are not directly compatible. We describe a suite of
      software tools built around the Common Assembly Format (CAF), a comprehensive
      representation of a sequence assembly as a text file. These tools form the
      backbone of sequencing informatics at the Sanger Centre and the Genome Sequencing
      Center. The CAF format is intentionally flexible, and our Perl and C libraries,
      which parse and manipulate it, provide powerful tools for creating new
      applications as well as wrappers to incorporate other software. The tools are
      available free by anonymous FTP from ftp://ftp.sanger.ac.uk/pub/badger/.

PMID- 9521930
TI  - EbEST: an automated tool using expressed sequence tags to delineate gene
      structure.
AB  - Large numbers of expressed sequence tags (ESTs) continue to fill public and
      private databases with partial cDNA sequences. However, using this huge amount of
      ESTs to facilitate gene finding in genomic sequence imposes a challenge,
      especially to wet-lab scientists who often have limited computing resources. In
      an effort to consolidate the information hidden in the vast number of ESTs into a
      readable and manageable format, we have developed EbEST-a program that automates
      the process of using ESTs to help delineate gene structure in long stretches of
      genomic sequence. The EbEST program consists of three functional modules-the
      first module separates homologous ESTs into clusters and identifies the most
      informative ESTs within each cluster; the second module uses the informative ESTs
      to perform gapped alignment and to predict the exon-intron boundary; and the
      third module generates text file and graphic outputs that illustrate the
      orientation, exonic structure, and untranslated regions (UTRs) of putative genes
      in the genomic sequence being analyzed. Evaluation of EbEST with 176 human genes
      from the ALLSEQ set indicated that it performed in-line with several existing
      gene finding programs, but was more tolerant to sequencing errors. Furthermore,
      when EbEST was challenged with query sequences that harbor more than one gene, it
      suffered only a slight drop in performance, whereas the performance of the other
      programs evaluated decreased more. EbEST may be used as a stand-alone tool to
      annotate human genomic sequences with EST-derived gene elements, or can be used
      in conjunction with computational gene-recognition programs to increase the
      accuracy of gene prediction. [EbBEST is available at http://EbEST.ifrc.mcw.edu]

PMID- 9521931
TI  - Alternative gene form discovery and candidate gene selection from gene indexing
      projects.
AB  - Several efforts are under way to partition single-read expressed sequence tag
      (EST), as well as full-length transcript data, into large-scale gene indices,
      where transcripts are in common index classes if and only if they share a common
      progenitor gene. Accurate gene indexing facilitates gene expression studies, as
      well as inexpensive and early gene sequence discovery through assembly of ESTs
      that are derived from genes that have not been sequenced by classical methods. We
      extend, correct, and enhance the information obtained from index groups by
      splitting index classes into subclasses based on sequence dissimilarity
      (diversity). Two applications of this are highlighted in this report. First it is
      shown that our method can ameliorate the damage that artifacts, such as
      chimerism, inflict on index integrity. Additionally, we demonstrate how the
      organization imposed by an effective subpartition can greatly increase the
      sensitivity of gene expression studies by accounting for the existence and tissue
      or pathology-specific regulation of novel gene isoforms and polymorphisms. We
      apply our subpartitioning treatment to the UniGene gene indexing project to
      measure a marked increase in information quality and abundance (in terms of
      assembly length and insertion/deletion error) after treatment and demonstrate
      cases where new levels of information concerning differential expression of
      alternate gene forms, such as regulated alternative splicing, are discovered.
      [Tables 2 and 3 can be viewed in their entirety as Online Supplements at
      http://www.genome.org.]

PMID- 9521932
TI  - BioViews: Java-based tools for genomic data visualization.
AB  - Visualization tools for bioinformatics ideally should provide universal access to
      the most current data in an interactive and intuitive graphical user interface.
      Since the introduction of Java, a language designed for distributed programming
      over the Web, the technology now exists to build a genomic data visualization
      tool that meets these requirements. Using Java we have developed a prototype
      genome browser applet (BioViews) that incorporates a three-level graphical view
      of genomic data: a physical map, an annotated sequence map, and a DNA sequence
      display. Annotated biological features are displayed on the physical and sequence
      based maps, and the different views are interconnected. The applet is linked to
      several databases and can retrieve features and display hyperlinked textual data
      on selected features. In addition to browsing genomic data, different types of
      analyses can be performed interactively and the results of these analyses
      visualized alongside prior annotations. Our genome browser is built on top of
      extensible, reusable graphic components specifically designed for bioinformatics.
      Other groups can (and do) reuse this work in various ways. Genome centers can
      reuse large parts of the genome browser with minor modifications, bioinformatics
      groups working on sequence analysis can reuse components to build front ends for
      analysis programs, and biology laboratories can reuse components to publish
      results as dynamic Web documents.

PMID- 9521933
TI  - SeqHelp: a program to analyze molecular sequences utilizing common computational
      resources.
AB  - Here we describe a tool to analyze molecular sequences utilizing the internet and
      existing computational resources for molecular biology. The computer program
      SeqHelp organizes information from database searches, gene structure prediction,
      and other information to generate multiply aligned, hypertext-linked reports to
      allow for fast analysis of molecular sequences. The efficient and economical
      strategy in this program can be employed to study molecular sequences for gene
      cloning, mutation analysis, and identical sequence search projects.

PMID- 9521934
TI  - Kaleidaseq: a Web-based tool to monitor data flow in a high throughput sequencing
      facility.
AB  - Tracking data flow in high throughput sequencing is important in maintaining a
      consistent number of successfully sequenced samples, making decisions on
      scheduling the flow of sequencing steps, resolving problems at various steps and
      tracking the status of different projects. This is especially critical when the
      laboratory is handling a multitude of projects. We have built a Web-based data
      flow tracking package, called Kaleidaseq, which allows us to monitor the flow and
      quality of sequencing samples through the steps of preparation of library plates,
      plaque-picking, preparation of templates, conducting sequencing reactions,
      loading of samples on gels, base-calling the traces, and calculating the quality
      of the sequenced samples. Kaleidaseq's suite of displays allows for outstanding
      monitoring of the production sequencing process. The online display of current
      information that Kaleidaseq provides on both project status and process queues
      sorted by project enables accurate real-time assessment of the necessary samples
      that must be processed to complete the project. This information allows the
      process manager to allocate future resources optimally and schedule tasks
      according to scientific priorities. Quality of the sequenced samples can be
      tracked on a daily basis, which allows the sequencing laboratory to maintain a
      steady performance level and quickly resolve dips in quality. Kaleidaseq has a
      simple easy-to-use interface that allows access to all major functions and
      process queues from one Web page. This software package is modular and designed
      to allow additional processing steps and new monitoring variables to be added and
      tracked with ease. Access to the underlying relational database is through the
      Perl DBI interface, which allows for the use of different relational databases.
      Kaleidaseq is available for free use by the academic community from
      http://www.cshl.org/kaleidaseq.

PMID- 9521935
TI  - Identification of human gene core promoters in silico.
AB  - Identification of the 5'-end of human genes requires identification of functional
      promoter elements. In silico identification of those elements is difficult
      because of the hierarchical and modular nature of promoter architecture. To
      address this problem, I propose a new stepwise strategy based on initial
      localization of a functional promoter into a 1- to 2-kb (extended promoter)
      region from within a large genomic DNA sequence of 100 kb or larger and further
      localization of a transcriptional start site (TSS) into a 50- to 100-bp
      (corepromoter) region. Using positional dependent 5-tuple measures, a quadratic
      discriminant analysis (QDA) method has been implemented in a new program
      CorePromoter. Our experiments indicate that when given a 1- to 2-kb extended
      promoter, CorePromoter will correctly localize the TSS to a 100-bp interval
      approximately 60% of the time. [Figure 3 can be found in its entirety as an
      online supplement at http://www.genome.org.]

PMID- 9521936
TI  - Minimal head trauma in children revisited: is routine hospitalization required?
AB  - OBJECTIVE: Children with a question of occult head injury are routinely
      hospitalized despite having both normal central nervous system (CNS) and computed
      tomographic (CT) scan examinations. We determined the incidence of significant
      CNS morbidity after occult head injury to determine whether or not hospital
      admission was necessary in children after minimal head trauma. METHODS: We
      reviewed the records of children admitted to a level I trauma center with a
      question of closed head injury, an initial Glasgow Coma Scale equal to 15, a
      normal neurologic exam, and a normal head CT scan. Children with associated
      injuries requiring admission were excluded. The endpoints were deterioration in
      CNS exam, new CT findings, and the need for a prolonged hospital stay. RESULTS:
      Sixty-two patients were studied with a mean age of 7 years (range, 1 month to 15
      years), and 65% were male. The primary mechanisms of injury were fall (45%) and
      vehicular crash (23%). The mean injury severity score was 4 +/- 2. The mean
      length of stay was 1.2 days (range, 1 to 3 days). Prolonged hospitalization
      occurred in 9 patients (15%). No child developed significant CNS sequelae
      warranting hospital admission. Total charges for these hospitalizations were $177
      874. CONCLUSIONS: Children undergoing emergency department work-up of occult head
      injury, who have a normal CNS exam and a normal head CT scan, do not seem to be
      at risk for significant CNS sequelae. These patients can be discharged home with
      parental supervision and avoid unnecessary and costly hospitalization.

PMID- 9521937
TI  - Evaluation of a bicycle helmet giveaway program--Texas, 1995.
AB  - OBJECTIVE: To determine the effect of a bicycle helmet giveaway program on helmet
      use among children. METHODS: In 1995, a bicycle helmet giveaway program was
      conducted in two rural towns in Texas. Helmets were given to all 403 school
      children in kindergarten through grade 8. Helmet education, a bicycle rodeo, and
      incentives to increase helmet use were part of the program. Observations of
      helmet use were made before the helmet program began and after the program at
      several intervals throughout the school year and during the summer. A self
      reported survey questionnaire was administered to children in grades 4 through 8
      before the helmet program began and at several intervals during the school year
      to determine their attitudes about helmet use, safety perceptions, and peer
      pressure. A questionnaire also was administered to the parents of these children
      to determine attitudes and bicycle helmet use among parents. RESULTS: Helmet use
      increased from 3% before the giveaway to 38% at the end of the school year, 7
      months later. However, during the subsequent summer, helmet use decreased to 5%.
      Helmet use among 7th- and 8th-grade students was 0% at all observations periods
      after the giveaway. Even though 96% of all students thought that helmet use
      increased riding safety and 68% thought helmets should be worn at all times when
      riding, only 25% thought that their friends would approve of helmet use. Most
      parents also believed that helmets increased riding safety and should be worn,
      but only 23% reported always wearing one when riding a bicycle. CONCLUSIONS:
      Bicycle helmet giveaway programs can increase helmet use temporarily, but they
      may not be sufficient to sustain it. This program was not effective among 7th-
      and 8th-grade students.

PMID- 9521938
TI  - Results of screening 1.9 million Texas newborns for 21-hydroxylase-deficient
      congenital adrenal hyperplasia.
AB  - OBJECTIVE: To assess results of newborn screening for 21-hydroxylase-deficient
      congenital adrenal hyperplasia (CAH) in Texas over 6 years of screening 1.9
      million infants. METHODS: In 1989, CAH was incorporated into the ongoing Texas
      Newborn Screening Program, which requires two screens on each newborn. 17
      Hydroxyprogesterone was assayed, without extraction, by radioimmunoassay of blood
      collected from heel sticks onto filter paper collection cards. Infants with
      elevated levels of 17-hydroxyprogesterone were referred for evaluation, and those
      considered to have CAH were studied with respect to disease characteristics. Data
      were collected by pediatric endocrinologists using standardized forms that
      included type of CAH, results of laboratory tests, treatment regimen, disease
      symptoms and signs, and, for girls, degree of genital virilization. RESULTS: The
      incidence of classic CAH in Texas is 1:16 008, with a ratio of salt-wasting to
      simple-virilizing of 2.7:1. A majority of infants detected were undiagnosed until
      screened, despite signs of salt-wasting or ambiguous genitalia. It was difficult
      to differentiate salt-wasting from simple-virilizing CAH in infants who were
      identified before the onset of adrenal insufficiency or electrolyte
      abnormalities. A substantial number of infants with nonclassic (NC) CAH also were
      detected. Not all infants were detected on the initial screen; 14% of infants
      with classic CAH and 87% with NC CAH were detected on the second routine
      screening test. CONCLUSIONS: Our findings confirm the benefits of newborn
      screening for CAH and the importance of a second screening test, and suggest that
      programs for newborn CAH screening must consider complex issues in diagnosis and
      treatment. These results also confirm that CAH is a continuum of disorders,
      rather than a disorder with discrete subtypes. In addition, the difficulties in
      differentiating CAH subtypes in newborns, and thus deciding appropriate
      treatment, and the high incidence of NC CAH suggest that standard diagnostic
      criteria and treatment regimens for CAH may need modification. Where screening
      exists, physicians will encounter more cases of CAH than in the past.

PMID- 9521939
TI  - Personal, financial, and structural barriers to immunization in socioeconomically
      disadvantaged urban children.
AB  - OBJECTIVE: To evaluate personal, financial, and structural barriers to
      vaccination in socioeconomically disadvantaged urban children in the first 2
      years of life. DESIGN: Prospective cohort study. SETTING: A large municipal
      teaching hospital in the Midwest. PARTICIPANTS: Healthy term newborns discharged
      to the care of their mothers. Mothers were interviewed 24 to 72 hours postpartum
      regarding personal and financial barriers, and 2 years later regarding personal,
      financial, and structural barriers to care. MAIN OUTCOME MEASURE: Vaccination
      status at age 2 years. RESULTS: Of 399 children with documented vaccination
      status, 47% had not received all recommended vaccinations by 2 years of age.
      After adjusting for mother's age, race, and education, mothers who were unmarried
      (adjusted odds ratio [AOR] 1.74; 95% confidence interval [CI]: 1.05, 2.90),
      multiparous (AOR 2.10; 95% CI: 1.26, 3.52), not coresident with the child's
      grandmother (AOR 1.75; 95% CI: 1.01, 3.03), had not received adequate prenatal
      care (AOR 1.78; 95% CI: 1.12, 2.84), or lived in poverty (AOR 2.62; 95% CI: 1.44,
      4.75) were more likely to have undervaccinated children, as were mothers who
      perceived less satisfaction with their child's health care (AOR 1.63; 95% CI:
      1.01, 2.61), less control over their lives (AOR 2.01; 95% CI: 1.03, 3.94), or
      more benefit of medical care to prevent vaccine-related diseases (AOR 1.76; 95%
      CI: 1.25, 2.48). CONCLUSIONS: Family environment, a mother's history of prenatal
      care use, and financial barriers are important factors related to vaccination
      receipt among socioeconomically disadvantaged children at age 2 years. These
      factors, however, do not fully explain the variation in vaccination status.

PMID- 9521942
TI  - Persistent low immunization coverage among inner-city preschool children despite
      access to free vaccine.
AB  - OBJECTIVE: To compare vaccination coverage among children 19 to 35 months of age
      from public housing developments where a free vaccine outreach program was in
      place with children residing elsewhere in the city. DESIGN: A household survey
      using a multistage cluster sampling method to compare community areas which
      accounted for 80% of measles cases during 1989 (high-risk stratum), areas which
      accounted for the remaining 20% of cases (low-risk stratum), and public housing
      developments (public housing stratum) having free, on-site vaccination services.
      SETTING: Inner-city Chicago households, April to May 1994. OUTCOME VARIABLES:
      Antigen-specific and series-specific coverage based on written records. RESULTS:
      Based on evaluation of 1244 children, citywide coverage for four doses of
      diphtheria-tetanus-pertussis vaccine, three doses of polio vaccine, and one dose
      of measles-containing vaccine (4:3:1) was 47% [95% confidence interval (CI), 40%
      to 55%]. Coverage was significantly lower among children residing in public
      housing (23%; 95% CI, 18% to 28%) compared with those residing in high-risk
      strata (45%; 95% CI, 38% to 52%) and low-risk strata (51%; 95% CI, 43% to 60%).
      Compared with white children (53%), coverage for the 4:3:1 series was lower among
      African-American children in public housing (29%) or outside public housing
      (36%). Moreover, 11% (95% CI, 8% to 14%) of children residing in public housing
      had never received any immunizations. CONCLUSIONS: African-American children
      throughout Chicago, particularly in public housing, remain at increased risk for
      vaccine-preventable diseases and should be targeted further for vaccination
      services. Vaccination coverage remains low several years after a major outbreak
      of measles and implementation of a free vaccine outreach program. Cluster surveys
      may be useful for monitoring vaccination coverage in high-risk urban settings.

PMID- 9521943
TI  - Acute otitis media in children with bronchiolitis.
AB  - OBJECTIVE: We investigated the prevalence and the etiology of acute otitis media
      (AOM) in children with bronchiolitis to determine whether AOM in such children is
      due entirely or mainly to respiratory syncytial virus (RSV), in which case
      routine antimicrobial treatment would not be appropriate. METHODS: The study
      group consisted of children aged 2 to 24 months with bronchiolitis. In patients
      with AOM at entry, nasal washings for RSV enzyme-linked immunosorbent assay were
      obtained, and Gram-stained smear, bacterial culture, and reverse transcriptase
      polymerase chain reaction to detect the presence of RSV were performed on middle
      ear aspirates. Patients without AOM were reevaluated at 48 to 72 hours, 8 to 10
      days, and 18 to 22 days. RESULTS: Forty-two children with bronchiolitis were
      enrolled. Sixty-two percent had AOM at entry or developed AOM within 10 days. An
      additional 24% had or eventually developed otitis media with effusion. Only 14%
      remained free of both AOM and otitis media with effusion throughout the 3-week
      observation period. All patients with AOM had 1 or more bacterial pathogens
      isolated from one or both middle-ear aspirates. Of 33 middle-ear aspirates,
      Streptococcus pneumoniae was isolated in 15, Haemophilus influenzae in 8,
      Moraxella catarrhalis in 8, and Staphylococcus aureus in 2. Two middle-ear
      aspirates yielded 2 pathogens each; 2 aspirates had no growth. RSV was identified
      in 17 (71%) of 24 patients with AOM. CONCLUSION: Bacterial AOM is a complication
      in most children with bronchiolitis. Accordingly, in patients with bronchiolitis
      and associated AOM, antimicrobial treatment is indicated.

PMID- 9521940
TI  - Three-year follow-up of vaccine response in extremely preterm infants.
AB  - OBJECTIVE: To assess whether the adequate antibody response observed in former
      extremely premature infants after the primary series of immunizations is
      sustained after the first booster vaccines. SUBJECTS AND METHODS: Sixteen former
      extremely premature (<29 weeks, <1000 g at birth) and 17 former full-term (>37
      weeks) infants had sera obtained for antibody titer measurement at 3 to 4 years
      of age. All had received the primary series and first booster vaccines for
      diphtheria, pertussis, tetanus, polio, and Haemophilus influenzae type b. Twelve
      preterm and 14 full-term children had completed the hepatitis B vaccine series.
      RESULTS: At 3 to 4 years of age, former preterm and full-term children had
      similar geometric mean titer (GMT) values of antibodies to tetanus, diphtheria,
      and pertussis. Preterm children had a lower GMT value of Haemophilus
      polyribosylribitol phosphate (PRP) antibody than did full-term children (0.99 vs
      3.06 microg/mL). Fifty percent of preterm and 88% of full-term children had PRP
      antibody >1.0 microg/mL; 100% of preterm and 94% of full-term children had anti
      PRP titers >0.15 microg/mL. GMT values of neutralizing antibodies to polio
      serotypes 1 and 2 were similar, with 94% to 100% of both groups above protective
      levels (>/=1:8). The difference in GMT values of polio serotype 3 approached
      significance (29 vs 73); fewer preterm children had protective titer values (75%
      vs 100%). Among children vaccinated against hepatitis B, 75% of preterm and 71%
      of full-term children were protected (10 mIU/mL). CONCLUSIONS: Preterm children
      immunized at the recommended chronological ages displayed antibody responses
      similar to those for full-term children for most immunizing antigens. Responses
      to PRP and polio serotype 3 were less robust than those of full-term children.

PMID- 9521941
TI  - Safety and immunogenicity of heptavalent pneumococcal vaccine conjugated to
      CRM197 in United States infants.
AB  - OBJECTIVE: To determine the safety and immunogenicity of heptavalent pneumococcal
      saccharide vaccine (serotypes 4, 6B, 9V, 14, 18C, 19F, 23F) individually
      conjugated to CRM197 (PNCRM7), administered at 2, 4, 6, and 12 to 15 months of
      age. DESIGN: Two hundred twelve healthy 2-month-old infants were equally
      randomized to receive four consecutive doses of PNCRM7 or an investigational
      meningococcal group C conjugate vaccine, which served as a control. Concomitantly
      administered routine vaccines were oral polio vaccine and combined diphtheria
      toxoid, tetanus toxoid, and whole cell pertussis vaccine/Haemophilus influenzae
      type b vaccine consisting of capsular oligosaccharides conjugated to CRM197
      (DTP/HbOC) at 2, 4, and 6 months, and either measles-mumps-rubella vaccine or
      HbOC at 12 to 15 months. Active safety surveillance was conducted for 3 days
      after each dose. Antibody concentrations to each of the 7 pneumococcal serotypes
      were measured by enzyme-linked immunosorbent assay prevaccination, after doses
      two and three, prebooster, and postbooster. RESULTS: Significantly fewer children
      experienced local reactions at the PNCRM7 injection site than at the DTP/HbOC
      site. There was no increase in the incidence or severity of local reactions at
      the PNCRM7 site with increasing doses of vaccine. Mild to moderate
      postvaccination fever was common in both the PNCRM7 and control vaccine groups,
      however DTP/HbOC was administered concurrently. All 7 vaccine serotypes were
      immunogenic. The kinetics of the immune responses were serotype-specific. After
      three doses of PNCRM7, between 92% to 100% of children had >/=0.15 microg/mL of
      antibody, and 51% to 90% achieved a level of >/=1 microg/mL against specific
      serotypes. A booster dose of PNCRM7 resulted in a brisk anamnestic response to
      all 7 vaccine serotypes, demonstrating effective stimulation of T-cell memory by
      the primary series of vaccinations. CONCLUSION: Primary immunization followed by
      a booster dose of PNCRM7 seemed to be acceptably safe and resulted in significant
      rises in antibody to all 7 serotypes. Implications. Studies to assess vaccine
      efficacy of PNCRM7 for prevention of systemic disease, nasopharyngeal
      colonization, and acute otitis media are in progress. If PNCRM7 proves to be
      protective, there is the potential to prevent up to 85% of invasive pneumococcal
      disease occurring in US children.

PMID- 9521944
TI  - Does child abuse predict adolescent pregnancy?
AB  - OBJECTIVE: To determine whether sexual and nonsexual childhood abuse are risk
      factors for early adolescent sexual activity and pregnancy. DESIGN; Cross
      sectional study. SETTING: Prenatal clinic within an inner-city teaching hospital
      from June 1990 to August 1991. POPULATION: One thousand twenty-six primiparous,
      African-American women enrolled in a randomized clinical trial of nurse home
      visitation. MAIN OUTCOME MEASURES: Four measures of child abuse were used: sexual
      abuse, incidents of physical abuse, any major physical abuse, and emotional
      abuse. The outcome measures were age of first consensual coitus and age of first
      pregnancy. RESULTS: After adjustments for household income, parental separation,
      urban residence, age of menarche, and teen smoking, sexual abuse during childhood
      was associated with younger age at first coitus (7.2 months; 95% confidence
      interval [CI], 2.6 to 11.7 months) and younger age at first pregnancy (9.7
      months; 95% CI, 3.0 to 16.3 months). Incidents of physical abuse showed minimal
      effect on age at first coitus (1.2 days per incident; 95% CI, 0.5 to 1.9 days)
      and no effect on age of first pregnancy. A history of major physical abuse or
      emotional abuse showed no effect on age of first coitus or first pregnancy.
      CONCLUSION: Child sexual abuse, but not child physical or emotional abuse, seems
      to be a risk factor for earlier pregnancy among African-American adolescents.

PMID- 9521945
TI  - Child fatalities from religion-motivated medical neglect.
AB  - OBJECTIVE: To evaluate deaths of children from families in which faith healing
      was practiced in lieu of medical care and to determine if such deaths were
      preventable. DESIGN: Cases of child fatality in faith-healing sects were
      reviewed. Probability of survival for each was then estimated based on expected
      survival rates for children with similar disorders who receive medical care.
      PARTICIPANTS: One hundred seventy-two children who died between 1975 and 1995 and
      were identified by referral or record search. Criteria for inclusion were
      evidence that parents withheld medical care because of reliance on religious
      rituals and documentation sufficient to determine the cause of death. RESULTS:
      One hundred forty fatalities were from conditions for which survival rates with
      medical care would have exceeded 90%. Eighteen more had expected survival rates
      of >50%. All but 3 of the remainder would likely have had some benefit from
      clinical help. CONCLUSIONS: When faith healing is used to the exclusion of
      medical treatment, the number of preventable child fatalities and the associated
      suffering are substantial and warrant public concern. Existing laws may be
      inadequate to protect children from this form of medical neglect.

PMID- 9521946
TI  - Neurodevelopmental outcomes in children with Fontan repair of functional single
      ventricle.
AB  - OBJECTIVES: The purpose of this study was to assess the neurodevelopmental status
      of children after Fontan repair of functional single ventricle and to examine the
      relationship between cognitive function and selected patient characteristics.
      STUDY DESIGN: Neurodevelopmental tests including the Stanford-Binet Intelligence
      (IQ) scale and the Developmental Test of Visual Motor Integration (VMI) were
      administered to 32 children (26 months to 16 years of age) with complex single
      ventricle. The mean and distribution of IQ and VMI scores were compared with
      population norms. The relationship between test scores and patient
      characteristics was examined utilizing analysis of variance and correlational
      methods. RESULTS: The majority of children had intellectual function within the
      normal range (mean, 97.5 +/- 12.1). Below average VMI scores were found in 21.4%
      of children. There were no significant correlations between intellectual function
      or visual motor integration ability and preoperative oxygen saturation or age at
      Fontan. Children who had deep hypothermic circulatory arrest during a prior
      Norwood procedure tended to have a lower IQ score. CONCLUSIONS: Intellectual
      development in children with Fontan repair of complex heart defects is
      essentially within the normal range. Visual motor integration deficits may be
      more prevalent in these children. In our population, the duration and degree of
      preoperative hypoxemia had no apparent effect on cognitive function.

PMID- 9521947
TI  - Helicobacter pylori and abdominal symptoms: a population-based study among
      preschool children in southern Germany.
AB  - OBJECTIVE: To determine the relation of Helicobacter pylori infection with
      gastrointestinal symptoms in a healthy population-based sample of children.
      DESIGN: Population-based cross-sectional study of preschool children. SETTING:
      Screening examination for school fitness by physicians of the Public Health
      Service in Ulm, a city with 100 000 inhabitants in southern Germany.
      PARTICIPANTS: One thousand two hundred one preschool children. MAIN OUTCOME
      MEASURES: Infection status was determined by 13C-urea breath test. Information on
      gastrointestinal symptoms was collected from children's parents by a standardized
      questionnaire and integrated into a symptom score. Results. Nine hundred forty
      five children participated in the study (response rate, 79%). Overall, 127
      children (13.4%) were infected. H pylori infection was not positively related to
      specific gastrointestinal symptomatology. Infected children had even fewer
      symptoms when compared with uninfected children. CONCLUSIONS: Our results
      indicate that H pylori infection in children is mostly asymptomatic and not
      associated with specific gastrointestinal symptoms.

PMID- 9521948
TI  - Treatment of aural foreign bodies in children.
AB  - OBJECTIVE: To determine the proper treatment of children and adolescents with
      foreign bodies of the external auditory canal (EAC). DESIGN: Retrospective case
      series. SETTING: Specialty care referral hospital. PATIENTS: All patients younger
      than 18 years of age who presented in the emergency ward or office setting with a
      foreign body of the EAC during a 5-year period. RESULTS: One hundred ninety-one
      patients with aural foreign bodies were identified. Age at presentation ranged
      from 10 months to 17 years with 141 patients (74%) younger than 8 years old.
      Twenty-seven different objects were encountered with pebbles, beads, insects, and
      plastic toys the most common. Fifty-seven (30%) of the patients required surgical
      removal of the aural foreign body under general anesthesia. CONCLUSION: Adequate
      immobilization and proper instrumentation allow the uncomplicated removal of many
      EAC foreign bodies in the pediatric population. The use of general anesthesia is
      preferred in very young children and in children of any age with aural foreign
      bodies whose contour, composition, or location predispose to traumatic removal in
      the ambulatory setting. Criteria for otolaryngologic referral and consideration
      of operative microscopic removal are outlined.

PMID- 9521949
TI  - Trends in mortality and cerebral palsy in a geographically based cohort of very
      low birth weight neonates born between 1982 to 1994.
AB  - OBJECTIVE: To analyze whether the increasing survival of very low birth weight
      infants during the 1980s and 1990s has increased the risk of cerebral palsy among
      survivors. METHODS: The study cohort consisted of 2076 consecutively born
      infants, with birth weights of 500 to 1500 g and no major anomaly, born July 1,
      1982, through June 30, 1994, to residents of a 17-county region in North
      Carolina. These infants had a mean birth weight of 1096 g (standard deviation,
      251 g) and a mean gestational age of 29 weeks (standard deviation, 3 weeks). One
      thousand five hundred sixty-eight infants (76%) survived to 1 year adjusted age,
      at which point 1282 infants (82%) were examined at our medical center. The
      diagnosis of cerebral palsy was made only if the examining pediatrician and a
      pediatric physical therapist agreed on the diagnosis. To analyze trends across
      time, the Cochran-Armitage chi2 test and logistic regression were applied to data
      for infants categorized into six 2-year epochs according to year of birth.
      RESULTS: Mortality did not change significantly through 1990, and then began to
      decrease in 1990 to 1994. During the study period, mortality decreased from 36.8%
      between 1982 and 1984, to 13.8% between 1992 and 1994. The prevalence of cerebral
      palsy among survivors was constant from 1982 to 1988 (11.3%), decreased slightly
      from 1988 to 1990 (9.2%), and was lowest in 1990 to 1994 (5.2%). These secular
      trends in mortality and cerebral palsy risk remained significant when adjusted
      for gestational age, gender, and race. When adjusted for surfactant use, the
      trend in mortality was no longer significant, whereas the trend in cerebral palsy
      risk persisted. CONCLUSIONS: The increasing survival of very low birth weight
      infants in the 1980s and 1990s has not resulted in an increased prevalence of
      cerebral palsy among survivors.

PMID- 9521951
TI  - Candida sepsis and association with retinopathy of prematurity.
AB  - OBJECTIVE: To assess the association of Candida sepsis with retinopathy of
      prematurity (ROP) in extremely low birth weight infants. METHODS: We
      prospectively identified 253 infants admitted to the Critical Care Nursery at
      Georgetown University Hospital with birth weights </=1000 g born between January
      1, 1994, and June 30, 1996. Of these 253 infants, 62 died and 55 were transferred
      to other institutions before ophthalmologic screening for ROP. Clinical data on
      98% (133/136) infants were reviewed. Candida sepsis was defined as a positive
      blood culture for Candida species. Severity of ROP was staged by the
      International Classification for ROP. Data were analyzed using the chi2 test for
      nominal data, unpaired t test for continuous data, Mann-Whitney U test for
      ordinal data, and logistic regression. RESULTS: The mean birth weight (+/-SD) of
      the population studied was 777 g (+/-136 g), and the mean gestational age at
      birth was 26.0 weeks (+/-1.8 weeks). The overall incidence of ROP was 74%, and it
      correlated significantly with birth weight, gestational age, days on supplemental
      oxygen, and 5-minute Apgar scores. The incidence of ROP was significantly higher
      in the infants who had Candida sepsis (21/22 [95%]) compared with those who did
      not (77/111 [69%]). Using logistic regression to control for the influence of
      birth weight, gestational age, days on supplemental oxygen, and 5-minute Apgar
      scores, Candida sepsis was an independent predictor of stage 3 or worse ROP. In
      addition, 9 (41%) of 22 infants with Candida sepsis required laser surgery
      compared with 10 (9%) of 111 infants without Candida sepsis. This difference was
      significant independent of birth weight, gestational age, days on supplemental
      oxygen, and 5-minute Apgar scores. CONCLUSIONS: Candida sepsis is independently
      associated with increased severity of ROP and the need for laser surgery in
      extremely low birth weight infants.

PMID- 9521950
TI  - Mainstream end-tidal carbon dioxide monitoring in the neonatal intensive care
      unit.
AB  - BACKGROUND: Continuous noninvasive monitoring of arterial carbon dioxide (CO2) in
      neonatal intensive care unit (NICU) patients would help clinicians avoid
      complications of hypocarbia and hypercarbia. End-tidal CO2 monitoring has not
      been used in this population to date, but recent technical advances and the
      introduction of surfactant therapy, which improves ventilation-perfusion
      matching, might improve the clinical utility of end-tidal monitoring. OBJECTIVE:
      To determine the accuracy and precision of end-tidal CO2 monitoring in NICU
      patients. DESIGN: Nonrandomized recording of simultaneous end-tidal and arterial
      CO2 pairs. SETTING: Two university NICUs. PATIENTS: Forty-five newborn infants
      receiving mechanical ventilation who had indwelling arterial access, and a
      predefined subsample of infants who were <1000 g birth weight, <8 days of age,
      and who received surfactant therapy (extremely low birth weight -ELBW- <8).
      OUTCOME MEASURES: The correlation coefficient, degree of bias, and 95% confidence
      interval were determined for both the overall population and the ELBW <8
      subgroup. Those factors which significantly influenced the bias were identified.
      The ability of the end-tidal monitor to alert the clinician to instances of
      hypocarbia or hypercarbia was determined. RESULTS: There were 411 end
      tidal/arterial pairs analyzed from 45 patients. The correlation coefficient was
      0.833 and the bias was -6. 9 mm Hg (95% confidence interval, +/-11.5 mm Hg). The
      results did not differ markedly in the ELBW <8 infants. Measures of the degree of
      lung disease, the ventilation index and the oxygenation index, had small
      influences on the degree of bias. This type of capnometry identified 91% of the
      instances when the arterial CO2 pressure was between 34 and 54 mm Hg using an end
      tidal range of 29 to 45 mm Hg. End-tidal values outside this range had a 63%
      accuracy in predicting hypocarbia or hypercarbia. CONCLUSION: End-tidal CO2
      monitoring in NICU patients is as accurate as capillary or transcutaneous
      monitoring but less precise than the latter. It may be useful for trending or for
      screening patients for abnormal arterial CO2 values.

PMID- 9521952
TI  - Single-dose and steady-state pharmacokinetics of a new oral suspension of
      ciprofloxacin in children.
AB  - OBJECTIVE: Quinolones are used ever increasingly in pediatrics, although
      officially they are still contraindicated. Lack of evidence of arthropathic
      effects in human offspring favors their use, but little is known about the
      pharmacokinetics of oral or parenteral ciprofloxacin in children, especially
      those without cystic fibrosis. DESIGN: We studied 16 non-cystic fibrosis patients
      ranging in age from 0.3 to 7.1 years to whom the new suspension formulation of
      ciprofloxacin (10 mg/kg body weight) was given orally three times daily. Single
      dose and steady-state pharmacokinetic parameters were elucidated. RESULTS:
      Ciprofloxacin was rapidly absorbed. The maximum plasma concentrations, with the
      means varying from 1.7 to 3.6 mg/L, were reached within 1 hour, almost regardless
      of whether single-dose administration or steady state. The mean oral clearance
      was lower in children <6 years of age than in those >/=6 years. Terminal half
      life values, with the means varying only between 4.2 and 5.1, suggest that dosing
      recommendations based on body weight are pertinent, although caution should be
      exercised in small infants. No arthropathic or other adverse events attributable
      to ciprofloxacin suspension were observed. CONCLUSION: A dose of the suspension
      form of ciprofloxacin of 10 mg/kg body weight given orally three times daily
      seems appropriate in children, provided the drug is clearly indicated.

PMID- 9521953
TI  - The growth pattern and final height of girls with Turner syndrome with and
      without human growth hormone treatment.
AB  - BACKGROUND: Shortness is the most frequent and quite disturbing characteristic of
      girls with Turner syndrome (TS). Human growth hormone administration (hGH) to
      girls with TS increases growth velocity (GV), but a favorable effect on final
      height (FH) has not been documented. The aim of this study was to evaluate the
      effect of hGH administration on the growth pattern and FH in girls with TS.
      METHODS: The study group was comprised of 123 girls with TS who were cared for in
      our center. Eighty-two of these girls received hGH (mean dose, 0.78 +/- 0.12
      IU/kg/week), given subcutaneously 5 to 7 times per week for a period of 2.2 +/-
      1.2 years (hGH group). The mean chronological age (CA) and bone age (BA) at hGH
      initiation were 11.5 +/- 2.5 years and 9.7 +/- 2.3 years, respectively. The
      remaining 41 girls did not receive hGH and are designated as the untreated
      control group. In both groups, gonadal steroids were given for pubertal
      initiation and maintenance. RESULTS: The GV during the first year of hGH therapy
      (GV1) was higher than the year before hGH (6.3 cm/year vs 4.0 cm/year) and higher
      than the GV of the untreated group at a similar CA (4.4 cm/year). The GVs during
      the second (GV2) and third (GV3) year of hGH treatment (5.4 and 4.9 cm/year,
      respectively) were lower, but still higher in the hGH group, in comparison with
      the untreated group (GV2, 4.2 cm/year; GV3, 3.4 cm/year). GV1, GV2, and GV3 were
      negatively related to age and to BA at hGH initiation. The FH of the 35 hGH
      treated girls was not significantly different from the FH of the 27 untreated
      girls (146.1 cm vs 144.0 cm). The Delta target height-FH was not significantly
      different in the two groups. The FH standard deviation score of the hGH-treated
      group was positively related to height standard deviation score for CA at
      treatment initiation (r = +0.73), maternal height (r = +0.57), target height (r =
      + 0.66), and birth weight (r = +0.54), but was unrelated to CA or BA at start of
      therapy or to hGH dose. CONCLUSIONS: hGH therapy in girls with TS, in the dose
      and duration of treatment applied in this study, significantly accelerated GV but
      did not significantly improve FH.

PMID- 9521954
TI  - Aggressors or victims: gender and race in music video violence.
AB  - OBJECTIVE: To examine portrayals of violence in popular music videos for patterns
      of aggression and victimization by gender and race. DESIGN AND SETTING: Content
      analysis of 518 music videos broadcast over national music television networks,
      Black Entertainment Television (BET), Country Music Television (CMT), Music
      Television (MTV), and Video Hits-1 (VH-1) during a 4-week period at randomly
      selected times of high adolescent viewership. MAIN OUTCOME MEASURES: Differences
      in the genders and races portrayed as aggressors and victims in acts of violence.
      RESULTS: Seventy-six (14.7%) of the analyzed music videos contained portrayals of
      individuals engaging in overt interpersonal violence, with a mean of 6.1 violent
      acts per violence-containing video. Among the 462 acts of violence, the music
      video's main character was clearly the aggressor in 80.1% and the victim in
      17.7%. In 391 (84.6%) of the violence portrayals, the gender of the aggressor or
      victim could be determined. Male gender was significantly associated with
      aggression; aggressors were 78.1% male, whereas victims were 46.3% female. This
      relationship was influenced by race. Among whites, 72.0% of the aggressors were
      male and 78.3% of the victims were female. Although blacks represent 12% of the
      United States population, they were aggressors in 25.0% and victims in 41.0% of
      music video violence. Controlling for gender, racial differences were significant
      among males; 29.0% of aggressors and 75.0% of victims were black. A logistic
      regression model did not find direct effects for gender and race, but revealed a
      significant interaction effect, indicating that the differences between blacks
      and whites were not the same for both genders. Black males were more likely than
      all others to be portrayed as victims of violence (adjusted odds ratio = 28.16,
      95% confidence interval = 8.19, 84.94). CONCLUSIONS: Attractive role models were
      aggressors in more than 80% of music video violence. Males and females were
      victims with equivalent frequency, but males were more than three times as likely
      to be aggressors. Compared with United States demographics, blacks were
      overrepresented as aggressors and victims, whereas whites were underrepresented.
      White females were most frequently victims. Music videos may be reinforcing false
      stereotypes of aggressive black males and victimized white females. These
      observations raise concern for the effect of music videos on adolescents'
      normative expectations about conflict resolution, race, and male-female
      relationships.

PMID- 9521956
TI  - Recent declines in New York City infant mortality rates.
AB  - BACKGROUND: Although infant mortality rates have declined gradually in New York
      City for many years, the rate of that decline began to accelerate dramatically at
      the end of the 1980s. OBJECTIVE: To analyze the recent accelerated decline in
      infant mortality for three race/ethnicity designations in New York City and to
      investigate whether shifts in birth weight distribution or changes in birth
      weight-specific death rates were more important in determining these declines
      between 1988 to 1989 and 1992 to 1993. METHODS: Two complete cohorts of linked
      birth-death certificate files consisting of all live births in New York City in
      1988 to 1989 and 1992 to 1993 were examined. For each cohort, separate
      multinomial logistic regressions were estimated by race/ethnicity to analyze the
      probability of a neonatal or postneonatal death relative to survival as a
      function of a spectrum of covariates. The coefficients from these regressions
      were used to construct direct and indirect standardization exercises to predict
      changes in infant mortality holding characteristics of the cohort, including
      birth weight distribution, constant over time, or holding the influence of
      determinants, including birth weight-specific death rates, constant over time.
      RESULTS: For whites, Hispanics, and blacks, infant mortality rates declined by
      27.4%, 24.8%, and 22.7%, respectively, between 1988 to 1989 and 1992 to 1993. For
      whites and blacks, the largest decreases occurred for neonatal mortality rates,
      whereas for Hispanics, postneonatal rates fell the greatest. Although infant
      mortality rates among very low birth weight infants (<1500 g) fell by 27.8%,
      19.3%, and 16.6% for whites, Hispanics, and blacks, the greatest decreases in
      rates were seen among normal birth weight infants (>2500 g). Infant mortality
      rate declines for this category of infants reached 31%, 31.7%, and 31.3%,
      respectively, for whites, Hispanics, and blacks. Direct and indirect
      standardization exercises indicated that the most important factor in determining
      these declines were decreases in birth weight-specific death rates, not
      improvements in the birth weight distribution over time. CONCLUSIONS: We conclude
      that the large decreases in infant mortality rates witnessed in New York City
      between 1988 to 1989 and 1992 to 1993 were attributable not to improvements in
      birth weight distribution of the population but to declines in birth weight
      specific death rates and that normal birth weight infants showed the greatest
      improvement.

PMID- 9521955
TI  - Treatment of symptomatic chronic adenotonsillar hypertrophy with
      amoxicillin/clavulanate potassium: short- and long-term results.
AB  - OBJECTIVE: To evaluate the short- and long-term effects of treatment of
      symptomatic chronic adenotonsillar hypertrophy (CATH) with a 30-day course of
      amoxicillin/clavulanate potassium (AMOX/CLAV). PATIENTS: Children 2 to 16 years
      of age with obstructive symptoms attributable to CATH, who did not have a history
      of recurrent adenotonsillitis. DESIGN: A prospective, randomized, double-blinded,
      placebo-controlled trial. SETTING: Ambulatory clinic of a tertiary care hospital.
      INTERVENTION: Patients were randomly treated with 30-day courses of either
      placebo (PLAC) or AMOX/CLAV (40 mg/kg in 3 divided doses daily). OUTCOME
      MEASURES: Patients' signs and symptoms were assessed by physical examination and
      by both physician and parental forced-choice questionnaires 1, 3, and 24 months
      after treatment. The decision to proceed to surgery or to continue expectant
      management was made for all patients by the same physician, based on reported
      symptoms and physical findings. RESULTS: Treatment with a 30-day course of
      AMOX/CLAV significantly reduced the need for surgery in the short term compared
      with PLAC (37.5% vs 62.7%) at 1-month follow-up). The reduced need for surgery in
      the AMOX/CLAV-treated group persisted at 3 months (AMOX/CLAV 54.5% vs PLAC 85.7%)
      and 24 months (AMOX/CLAV 83.3% vs PLAC 98.0%). CONCLUSIONS: A 30-day course of
      AMOX/CLAV significantly reduces the need for surgery in children with obstructive
      adenotonsillar hypertrophy at 1-month follow-up. This relative reduction persists
      at 3 and 24 months posttreatment, although the absolute percentages of patients
      requiring surgery increased in both groups as time after treatment increased. The
      reduction in symptoms in AMOX/CLAV-treated patients is modest but significant
      even in long-term follow-up. The precise role of this treatment for CATH is yet
      to be determined; however, our results suggest that a 30-day course of AMOX/CLAV
      can be used in situations when a temporary relief in symptoms is desirable or
      surgery would incur unacceptable risk.

PMID- 9521957
TI  - Inhaled nitric oxide: a tenth anniversary observation.

PMID- 9521958
TI  - Cooling the asphyxiated newborn-responsibly.

PMID- 9521959
TI  - Hemolytic uremic syndrome associated with invasive Streptococcus pneumoniae
      infection.

PMID- 9521960
TI  - Congenital myotonic dystrophy requiring prolonged endotracheal and noninvasive
      assisted ventilation: not a uniformly fatal condition.
AB  - In this report we present two infants with congenital myotonic dystrophy (CMD)
      who were successfully weaned from prolonged ventilatory support using nasal
      continuous positive airway pressure (N-CPAP). The first infant received 127 days
      of endotracheal mechanical ventilation as part of 141 days of total ventilatory
      support, including N-CPAP; the second infant received 27 days of endotracheal
      mechanical ventilation as part of 84 days of total ventilatory support.
      Noninvasive N-CPAP facilitated weaning these two infants from ventilatory
      support, thereby minimizing the morbidity associated with prolonged intubation.
      The developmental outcomes of our two infants were comparable to infants not
      requiring prolonged endotracheal mechanical ventilation. We suggest that this
      noninvasive modality of ventilatory support may be advantageous in the management
      and beneficial to the outcome of infants with CMD who are respirator-dependent
      >30 days.

PMID- 9521961
TI  - Cardiac disease in Costello syndrome.

PMID- 9521962
TI  - Succinyl-CoA:3-ketoacid CoA-transferase deficiency.

PMID- 9521963
TI  - Toxic effects of indoor molds. American Academy of Pediatrics. Committee on
      Environmental Health.
AB  - This statement describes molds, their toxic properties, and their potential for
      causing toxic respiratory problems in infants. Guidelines for pediatricians are
      given to help reduce exposures to mold in homes of infants. This is a rapidly
      evolving area and more research is ongoing.

PMID- 9521964
TI  - Medical necessity for the hospitalization of the abused and neglected child.
      American Academy of Pediatrics. Committee on Hospital Care and Committee on Child
      Abuse and Neglect.
AB  - The child suspected of being abused or neglected demands prompt evaluation in a
      protective environment where knowledgeable consultants are readily available. In
      communities without specialized centers for the care of abused children, the
      hospital inpatient unit becomes an appropriate setting for their initial
      management. Medical, psychosocial, and legal concerns may be assessed
      expeditiously while the child is housed in a safe haven awaiting final
      disposition by child protective services. The American Academy of Pediatrics
      recommends that hospitalization of abused and neglected children, when medically
      indicated or for their protection/diagnosis when there are no specialized
      facilities in the community for their care, should be viewed as medically
      necessary by both health professionals and third-party payors.

PMID- 9521965
TI  - Risk of ionizing radiation exposure to children: a subject review. American
      Academy of Pediatrics. Committee on Environmental Health.
AB  - Exposure of children to ionizing radiation most commonly is from the environment,
      chiefly through cosmic rays and radon, or from medical technology. Medical
      radiation exposure occurs during diagnosis, therapy, and dental radiography. More
      is known about the biological effects of exposure to ionizing radiation than to
      nonionizing radiation from microwaves, radiowaves, and the electrical fields of
      other electrical appliances. This review applies only to sources of ionizing
      radiation and does not include the potential risks of indoor radon. The effects
      on children of ionizing radiation have been studied from war activities and
      environmental accidents. Protections are mode from that data to help
      pediatricians evaluate risk from radiation when ordering radiographs.

PMID- 9521966
TI  - In-line skating injuries in children and adolescents. American Academy of
      Pediatrics. Committee on Injury and Poison Prevention and Committee on Sports
      Medicine and Fitness.
AB  - In-line skating has become one of the fastest-growing recreational sports in the
      United States. Recent studies emphasize the value of protective gear in reducing
      the incidence of injuries. Recommendations are provided for parents and
      pediatricians, with special emphasis on the novice or inexperienced skater.

PMID- 9521967
TI  - Guidance for effective discipline. American Academy of Pediatrics. Committee on
      Psychosocial Aspects of Child and Family Health.
AB  - When advising families about discipline strategies, pediatricians should use a
      comprehensive approach that includes consideration of the parent-child
      relationship, reinforcement of desired behaviors, and consequences for negative
      behaviors. Corporal punishment is of limited effectiveness and has potentially
      deleterious side effects. The American Academy of Pediatrics recommends that
      parents be encouraged and assisted in the development of methods other than
      spanking for managing undesired behavior.

PMID- 9521968
TI  - The collaborative UK ECMO (Extracorporeal Membrane Oxygenation) trial: follow-up
      to 1 year of age.
AB  - OBJECTIVE: To evaluate the clinical effectiveness of neonatal extracorporeal
      membrane oxygenation (ECMO), in terms of mortality and morbidity, in the
      treatment of cardiorespiratory failure in term infants. METHODS: The criteria for
      trial entry were: an oxygenation index of >40 or arterial partial pressure of
      carbon dioxide (PaCO2) >12 kPa for at least 3 hours; gestational age at birth of
      35 completed weeks or more; a birth weight of 2 kg or more; <10 days high
      pressure ventilation; an age of <28 days; and no contraindication to ECMO such as
      previous cardiac arrest or intraventricular hemorrhage. Eligible infants were
      randomized either to be transferred to one of five ECMO centers in the United
      Kingdom or to continue conventional treatment. The principal outcome was death or
      severe disability at the age of 1 year. Severe disability was defined as an
      overall developmental quotient of <50 using the Griffiths Mental Development
      Scales, or blindness or a level of function so as to make assessment using the
      Griffiths Scales impossible. Families of surviving children were contacted at
      regular intervals during the first year and at the age of 1, and an assessment of
      the child was performed by one of three developmental pediatricians. This
      included a neurologic examination, assessment of hearing and vision,
      developmental level, general health, and health service use. RESULTS: Of 185
      infants recruited into the trial, 93 infants were in the ECMO arm and 92 were
      allocated conventional treatment. The groups were comparable at trial entry.
      Thirty of 93 (32%) ECMO infants died before the age of 1 year and 54 of 92 (59%)
      of the infants in the conventional group died. Two infants were lost to follow
      up, 1 from each arm of the trial. Of the remaining 99 survivors, at the age of 1
      year, 2 infants (1 in each arm) were still in the hospital, and 5 (3 in the ECMO
      arm and 2 conventional) still required supplementary oxygen. Fifteen infants had
      tone changes in the limbs, 10/62 (16%) in the ECMO arm and 5/37 (13.5%) in the
      conventional arm. These signs were more common on the left side in both groups.
      One infant (in the ECMO arm) had bilateral sensorineural deafness and 1 infant
      (also in the ECMO arm) had low vision. Overall, 2 infants were severely disabled
      (1 ECMO and 1 conventional), 16 others also had evidence of functional loss (12
      vs 4), and 8 had impairment without functional loss (4 vs 5). There was a trend
      toward proportionately greater respiratory morbidity in the conventional group.
      Neurologic morbidity was more common in the ECMO group, reflecting the larger
      number of survivors. The lower rate of adverse primary outcome (death or severe
      disability at 1 year) was found among infants allocated ECMO in all the
      predefined stratified analyses. Disease severity at trial entry and type of
      referral center did not appear to alter the effects of ECMO. Only 4 of 18 infants
      with congenital diaphragmatic hernia survived and at age 1 year only 1 of the 4
      survivors was considered normal. CONCLUSION: These results are in accord with the
      earlier preliminary findings that a policy of ECMO support reduces the risk of
      death without a concomitant rise in severe disability. However, 1 in 4 survivors
      had evidence of impairment with or without disability. Further follow-up is
      planned at the age of 4 and 7 years.

PMID- 9521969
TI  - Telephone charges and payments in a diabetes clinic.
AB  - OBJECTIVES: To determine reimbursement rates after initiation of charges for
      certain telephone calls in a pediatric diabetes care center. DESIGN: A review of
      charges and payments data during 1996. RESULTS: Four hundred seventy-two
      telephone calls initiated by patients and parents were billed during the study
      period. These calls regarded treatment of hypoglycemia, hyperglycemia, ketonuria,
      sick day treatment, and insulin dose changes. Insured patients were charged for
      384 telephone calls and indigent patients were charged for 88 telephone calls.
      Telephone calls from insured patients generated charges of $9215 and payments of
      $3074. Insurance payments were $1677 (18% of charges), and patient payments were
      $1396 (15% of charges). Telephone calls from uninsured patients covered by Texas
      Medicaid or Chronically Ill and Disabled Children funding generated charges of
      $2193 and no payments. CONCLUSIONS: Telephone charges were reimbursed by all
      payors at an overall rate of 27%.

PMID- 9521970
TI  - Effectiveness and cost-effectiveness of letters, automated telephone messages, or
      both for underimmunized children in a health maintenance organization.
AB  - BACKGROUND: Immunization rates have improved in the United States, but are still
      far from the national 90% goal for the year 2000. There is scant evidence about
      the effectiveness and costs of automated telephone messages to improve
      immunization rates among privately insured children. OBJECTIVE: To evaluate the
      effectiveness and cost-effectiveness of sending letters, automated telephone
      messages, or both to families of underimmunized 20-month-olds in a health
      maintenance organization (HMO). METHODS: In this randomized trial, underimmunized
      20-month-olds identified by the HMO's computerized immunization tracking system
      were assigned to one of four interventions: 1) an automated telephone message
      alone; 2) a letter alone; 3) an automated telephone message followed by a letter
      1 week later; and 4) a letter followed by an automated telephone message 1 week
      later. The primary outcome was receipt of any needed immunization by 24 months of
      age. Decision analysis was used to evaluate the projected cost-effectiveness of
      the alternative strategies. RESULTS: A total of 648 children were randomized. A
      letter followed by a telephone message (58% immunized) was significantly better
      than either a letter alone (44% immunized) or a telephone message alone (44%
      immunized). A telephone message followed by a letter (53% immunized) also was
      more effective than either alone, although the differences were not statistically
      significant. Among a similar comparison group that received no systematic
      intervention, 36% were immunized. The estimated cost per child immunized was
      $7.00 using letters followed by automated telephone messages, $9.80 using
      automated telephone messages alone, and $10.50 using letters alone. Under
      alternative cost assumptions for automated telephone messages and mailed
      messages, the cost per child immunized ranged from $2.20 to $6.50. CONCLUSIONS:
      For underimmunized 20-month-olds in this HMO setting, letters followed by
      automated telephone messages were more effective and cost-effective than either
      message alone. The cost-effectiveness of automated telephone messages and letters
      may vary widely depending on the setting, and choices among strategies should be
      tailored to the populations being served.

PMID- 9521971
TI  - Analgesia for neonatal circumcision: a randomized controlled trial of EMLA cream
      versus dorsal penile nerve block.
AB  - OBJECTIVE: To compare the efficacy of the dorsal penile nerve block (DPNB) with a
      less invasive form of local anesthesia, eutectic mixture of local anesthetic
      (EMLA) cream, for reduction of pain during neonatal circumcision. DESIGN:
      Prospective, blinded, randomized, controlled trial. SETTING: Tertiary referral,
      neonatal intensive care nursery in a university teaching hospital. PATIENTS:
      Fifty infants >/=341/2 weeks postmenstrual age and stable for discharge at time
      of circumcision; gestational age at birth 25 to 41 weeks; birth weight 600 to
      4390 g; age at study 3 to 105 days. An additional cohort of term newborns (n =
      20), who were not randomized, were circumcised without anesthesia. INTERVENTIONS:
      Administration of either EMLA cream (0.5 g topically 1 hour before circumcision)
      or 1% lidocaine (0.7-1.0 mL subcutaneously 3 minutes before circumcision).
      OUTCOME MEASURES: Primary: Neonatal Infant Pain Scale (NIPS) score; secondary:
      heart rate, respiratory rate. All outcome measures were assessed by an individual
      who was blinded to the group assignment and did not perform the circumcision.
      RESULTS: NIPS scores were significantly lower in the DPNB infants (2.3 +/- 1.8)
      compared with the EMLA infants (4.8 +/- 0.7). NIPS scores in patients circumcised
      without anesthesia indicated severe pain. There was a significantly greater
      increase in heart rate over the duration of the circumcision in the EMLA group
      than in the DPNB group (49 vs 9 beats per minute). Adverse effects included small
      hematomas at the site of injection in DPNB infants (10/23), mild erythema at 1
      and/or 24 hours after circumcision in the EMLA infants (3/21), and penile edema
      noted 5 days after circumcision requiring removal of the circumcision bell in 1
      DPNB infant. CONCLUSIONS: DPNB provides better pain reduction during neonatal
      circumcision than EMLA cream. EMLA cream may provide pain reduction compared with
      no anesthesia during neonatal circumcision.

PMID- 9521973
TI  - Long-term outcome after neonatal meconium obstruction.
AB  - OBJECTIVE: It is unclear whether children with cystic fibrosis (CF) who present
      with neonatal meconium ileus have a different long-term outcome from those
      presenting later in childhood with pulmonary complications or failure to thrive.
      We examined a cohort of patients with meconium ileus, and compared their long
      term outcome with children who had CF without meconium ileus and neonates who had
      meconium obstruction without CF (meconium plug syndrome). STUDY DESIGN:
      Comparative study using retrospective and follow-up interview data. PATIENTS:
      Group 1 consisted of 35 surviving CF patients who presented with meconium ileus
      between 1966 and 1992. Two control groups were also studied: 35 age- and sex
      matched CF patients without meconium ileus (group 2), and 12 infants presenting
      with meconium plug syndrome during the same time period (group 3). OUTCOME
      MEASURES: Pulmonary, gastrointestinal, nutritional, and functional status were
      reviewed, and surgical complications were recorded. RESULTS: Mean follow-up was
      12.6 +/- 6, 12.6 +/- 6, and 9. 3 +/- 4 years in groups 1, 2, and 3, respectively.
      Patients without CF (group 3) demonstrated better growth and functional status,
      and had a lower incidence of pulmonary and gastrointestinal problems. Although
      the presence of meconium ileus among CF patients was associated with an earlier
      diagnosis, there were no significant differences between groups 1 and 2 with
      respect to hepatobiliary, nutritional, functional, or respiratory status.
      Meconium ileus was associated with a higher risk of meconium ileus equivalent
      (20% vs 6%), although this difference was not statistically significant. Long
      term surgical complications (adhesive small bowel obstruction and blind loop
      syndrome) were seen in 27% of children with meconium ileus; there were no long
      term surgical complications in groups 2 or 3, because these infants did not have
      any neonatal surgical procedures. Children presenting with complicated meconium
      ileus had a higher rate of long-term surgical complications than those with
      uncomplicated meconium ileus (36% vs 17%), and those managed with resection or
      enterostomy had more complications than those treated by enterotomy and lavage
      (33% vs 0%). CONCLUSIONS: Long-term outcome is similar in CF patients who present
      with meconium ileus and those who do not, except for a slightly higher incidence
      of meconium ileus equivalent, and a significantly higher rate of surgical
      complications. The risk of surgical complications is highest in those presenting
      with complicated meconium ileus and those undergoing resection or enterostomy.
      Patients with meconium obstruction who do not have CF have an excellent long-term
      prognosis. This information will be useful in counseling the families of infants
      presenting with neonatal meconium obstruction.

PMID- 9521974
TI  - Anaphylaxis in children: clinical and allergologic features.
AB  - BACKGROUND: Despite the importance of anaphylaxis, little information is
      available on its clinical features. OBJECTIVE: To evaluate the clinical and
      allergologic features of anaphylaxis in children referred to the allergology and
      immunology unit of A. Meyer Children's Hospital (Florence, Italy) from 1994 to
      1996. RESULTS: Ninety-five episodes of anaphylaxis occurred in 76 children (50
      boys and 26 girls). Sixty-six children (87%) had only one episode of anaphylaxis,
      while 10 (13%) had two or more episodes. Sixty-two (82%) of the 76 patients had a
      personal history of atopic symptoms, although 14 (18%) did not. Sixty (79%) of
      the 76 children studied had at least one positive skin prick test to one or more
      of the common inhalant and/or food allergens. Children with venom-induced
      anaphylaxis usually had negative skin tests to the allergens tested. A younger
      age and eczema were more frequent among children with food-dependent anaphylaxis,
      whereas an older age together with urticaria-angioedema were common among those
      with exercise-induced anaphylaxis. The mean latent period (+/-SD) of the
      anaphylaxis episodes was 15.4 +/- 27.5 minutes. Skin and respiratory
      manifestations had an earlier onset and were more common than the
      gastrointestinal and cardiovascular ones. The most frequent clinical
      manifestation in children with food anaphylaxis was gastrointestinal symptoms,
      whereas cardiovascular symptoms were rare. The most probable causative agents in
      the 95 episodes described were foods (57%), drugs (11%), hymenoptera venom (12%),
      exercise (9%), additives (1%), specific immunotherapy (1%), latex (1%), and
      vaccines (2%), but in 6 cases (6%) the agent was never determined. Among the
      foods, seafood and milk were the most frequently involved. As for location, 57%
      of the anaphylactic events occurred in the home (54/95), 12% outdoors (11/95); 5%
      in restaurants (5/95); 3% in the doctor's office (3/95); 3% in hospitals (3/95);
      3% on football fields (3/95); 2% on the beach (2/95); 1% in the gym (1/95); 1% at
      school (1/95); and 1% in the operating room (1/95). In the remaining 12% of cases
      (11/95) the site remained unknown. Sixty-two percent of the patients (59/95) were
      treated in an emergency room or hospital, while 32% (30/95) were not (this
      information is lacking in 6% of the cases [6/95]). Patients were treated with
      corticosteroids in 72% of the cases (68/95), with antihistamines in 20% (19/95),
      with epinephrine in 18% (17/95), with beta2-agonists in 5% (5/95), and with
      oxygen in 4% (4/95). CONCLUSIONS: In our area, foods, particularly seafood and
      milk, seem to be the most important etiologic factors triggering anaphylaxis.
      Food-induced anaphylaxis often occurs in younger children with a severe food
      allergy, whereas exercise-induced anaphylaxis occurs more often in older children
      with a history of urticaria-angioedema. The venom-induced variant usually
      presents itself in nonatopic subjects. Given the fact that most of the children
      had only one anaphylactic reaction, prevention is almost impossible. Epinephrine,
      although it is the first-choice treatment of anaphylaxis, often goes unused, even
      in hospitals and doctors' offices.

PMID- 9521975
TI  - Normative sexual behavior in children: a contemporary sample.
AB  - OBJECTIVE: Sexual behavior in children can cause uncertainty in the clinician
      because of the relationship between sexual abuse and sexual behavior.
      Consequently, it is important to understand normative childhood sexual behavior.
      DESIGN: Sexual behavior in 1114 2- to 12-year-old children was rated by primary
      female caregivers. These children were screened for the absence of sexual abuse.
      A 38-item scale assessing a broad range of sexual behavior (Child Sexual Behavior
      Inventory, Third Version) was administered along with the Child Behavior
      Checklist and a questionnaire assessing family stress, family sexuality, social
      maturity of the child, maternal attitudes regarding child sexuality, and hours in
      day care. RESULTS: Sexual behavior was related to the child's age, maternal
      education, family sexuality, family stress, family violence, and hours/week in
      day care. Frequencies of sexual behaviors for 2- to 5-, 6- to 9-, and 10- to 12
      year-old boys and girls are presented. CONCLUSIONS: A broad range of sexual
      behaviors are exhibited by children who there is no reason to believe have been
      sexually abused. Their relative frequency is similar to two earlier studies, and
      this reinforces the validity of these results.

PMID- 9521976
TI  - Congenital anomalies in the offspring of mothers with a bicornuate uterus.
AB  - BACKGROUND: Most of the reports on mothers with bicornuate uterus analyze
      fertility, reproductive capacity, and pregnancy outcomes. Very few of them,
      however, mention the risk for congenital anomalies in their offspring. Further,
      to our knowledge, no epidemiologic studies estimating the risk for congenital
      defects and analyzing the type of anomalies observed in infants born to mothers
      with bicornuate uterus have been reported. METHODS: Using a case-control study
      series, we estimated the risk of congenital anomalies in the offspring of women
      with a bicornuate uterus. To identify the specific defects associated with the
      presence of a bicornuate uterus in the mother, we analyzed 26 945 consecutive
      malformed infants from the Spanish Collaborative Study of Congenital
      Malformations and assessed the frequency of congenital anomalies in the offspring
      of mothers with a bicornuate uterus and in those born to mothers with a normal
      uterus. We then calculated the relative frequency, which is the quotient of the
      frequency of the individual defects in each group. This figure expresses the
      times each congenital defect is more frequent in infants of mothers with a
      bicornuate uterus than in those born to mothers with a normal uterus. RESULTS:
      Offspring of mothers with a bicornuate uterus had a risk for congenital defects
      four times higher than infants born to women with a normal uterus. The risk was
      statistically significant for some specific defects such as nasal hypoplasia,
      omphalocele, limb deficiencies, teratomas, and acardia-anencephaly. CONCLUSIONS:
      Offspring of mothers with bicornuate uterus are not only at high risk for
      deformations and disruptions, but also for some type of malformations.

PMID- 9521977
TI  - Benefits of neonatal screening for congenital adrenal hyperplasia (21-hydroxylase
      deficiency) in Sweden.
AB  - OBJECTIVES: The aim of this study was to evaluate the benefits of neonatal
      screening for congenital adrenal hyperplasia (CAH). METHODS: All children with
      CAH born in Sweden from January 1989 to December 1994 were subjected to a
      systematic follow-up. Clinical symptoms were recorded and laboratory data
      collected. The clinical diagnosis versus diagnosis by screening was investigated.
      The results were compared with those of a retrospective study of all patients
      diagnosed during 1969-1986 (before the introduction of neonatal screening).
      RESULTS: The prevalence of CAH in Sweden was 1:9800 with screening. Patients with
      CAH were identified earlier by screening. Half of the infants (47%) were not
      diagnosed at the time of recall, which was 8 days (median). In the study
      population, 25% of the girls and 73% of the boys were diagnosed by screening
      alone. The median age at the time of the definite diagnosis in boys was 21 days
      before screening as compared with 9 days (median) during the last part of the
      screening period. During the screening period, only 1 boy had a severe salt loss
      crisis, which occurred at the age of 8 days. Before screening, (1969-1986) 2 boys
      had died in the neonatal period because of an adrenal crisis. The lowest serum
      sodium recorded at the time of diagnosis was 124 mmol/L (median; range, 93-148)
      before, as compared with 134 mmol/L (median; range, 115-148) after the
      introduction of screening. The number of girls who were initially considered to
      be boys was not reduced by screening (17% vs 18%). The period of uncertainty
      regarding gender attributable to virilization was shortened considerably, as well
      as the time it took to make a correct gender assignment: 23 days (median) before
      screening versus 3 days (median) with screening. The maximum time it took to make
      the correct gender assignment was 960 days before screening and 14 days with
      screening. The number of patients diagnosed late, ie, after the first year of
      life, decreased considerably after the introduction of screening. The false
      positive rate (when a new filter paper blood sample was requested or when a child
      was referred to a pediatrician for follow-up) was <0.05% and in about 60% of the
      cases, it was attributable to preterm infants. The cost of screening was US
      dollar 2.70 per screened infant. CONCLUSION: The main benefits of screening were
      avoidance of serious salt loss crises, earlier correct gender assignment in
      virilized girls, and detection of patients who would have otherwise been missed
      in the neonatal period. Deaths in the neonatal period were prevented by
      screening. The aim of the screening program was to identify patients with the
      severe forms of CAH. Nevertheless, it must be considered a distinct benefit that
      a number of patients with milder forms of CAH were detected earlier, because
      earlier therapy results in decreased virilization, normalized growth and puberty,
      and, in all probability, an improved psychosocial situation for these children.
      We conclude that, in the Swedish health care system, the benefits of screening
      for CAH outweigh the costs.

PMID- 9521978
TI  - Cardiovascular disease insulin risk in Mexican-American and Anglo-American
      children and mothers.
AB  - OBJECTIVE: To evaluate the relationship between insulin levels and cardiovascular
      risk factors in children and determine whether it varies among ethnic groups.
      METHODS: Cardiovascular risk factors and insulin levels were compared in 144
      Mexican-American and Anglo-American mother-child pairs, when the children were 11
      years of age. RESULTS: Although mean age did not differ between ethnicities,
      Mexican-American mothers and children both had a greater body mass index
      (mothers: 29.2 +/- 6.2 vs 27.2 +/- 7.9; children: 21.7 +/- 4.7 vs 19.7 +/- 4.6)
      and sum of skinfolds than did Anglo-Americans. Triglycerides, very low-density
      lipoprotein cholesterol, fasting insulin, and cholesterol/high-density
      lipoprotein ratio were higher, while high-density lipoprotein cholesterol was
      lower in both Mexican-American adults and children compared with Anglo-Americans.
      After adjusting for measures of obesity, only high-density lipoprotein
      cholesterol levels remained significantly lower in Mexican-Americans. For both
      adults and children, higher quartiles of insulin levels were associated with
      significantly higher triglycerides, blood pressure and lower high-density
      lipoprotein cholesterol, and low-density lipoprotein cholesterol/apolipoprotein B
      levels (estimate of dense low-density lipoprotein size). A summary variable
      representing cardiovascular risk factors present in adult syndrome X patients was
      higher in both Mexican-American adults and children than in Anglo-Americans.
      CONCLUSION: Mexican-American children and adults have higher levels of many
      cardiovascular risk factors, and this appears related to higher insulin levels
      and overweight. Appropriate nutrition, weight control, and exercise at early ages
      could be important in slowing the development of atherosclerosis.

PMID- 9521979
TI  - Comparison of length of stay for asthma by hospital type.
AB  - OBJECTIVE: To determine whether length of stay (LOS) for asthma admissions at a
      local university-affiliated children's hospital (UACH) is similar to that of
      community hospitals within the same county. METHODS: A retrospective analysis was
      performed using computerized hospital abstract records from 1989 through 1994.
      The study population was children 1 to 18 years old whose first or only
      hospitalization for a primary diagnosis of asthma occurred during the study
      period at either the UACH or one of the 17 community hospitals in King County,
      WA, that admit pediatric patients (n = 2491). Transfers and patients with chronic
      obstructive asthma or secondary diagnoses such as cystic fibrosis were not
      included in the study. Asthma patients were compared by sociodemographic and
      health risk characteristics such as age, sex, insurance status, and a comorbidity
      severity score. Differences between the two hospital populations were tested by
      chi2 and t tests. The effect of hospitalization at the UACH or the community
      hospitals on LOS was determined using analysis of covariance after adjusting for
      the sociodemographic and health risk covariates. RESULTS: Sixty-two percent (62%)
      of the asthma patients in the study population were discharged from the UACH.
      Compared with patients discharged from the community hospitals, the UACH patients
      were significantly younger, more often male, used public insurance, and resided
      in areas with lower median household incomes. The severity of comorbidities was
      not different between the two hospital groups. Overall, adjusted mean LOS was not
      significantly longer at the UACH (2.1 days) than at the community hospitals (2.0
      days); however, adjusted mean LOS for specific subgroups, most notably poor
      children and those with public insurance, was significantly longer at the UACH.
      CONCLUSION: LOS for first or only asthma hospitalizations during 1989 through
      1994 at the UACH was similar to local community hospitals within the same county.
      Specific subgroups of children were hospitalized for a longer period at the UACH,
      but children with private insurance and from areas with higher median household
      incomes had similar LOS, and presumably costs, at the UACH and the community
      hospitals.

PMID- 9521980
TI  - Effect of reperfusion on biventricular function and survival after right
      ventricular infarction.
AB  - BACKGROUND: Although the salutary effects of reperfusion in patients with left
      ventricular infarction are well documented, the benefits in patients with acute
      right ventricular infarction are less clear. METHODS: To determine whether
      primary angioplasty improves right ventricular function and the clinical outcome
      in patients with right ventricular infarction, we performed echocardiographic
      studies before and after angioplasty in 53 patients with acute right ventricular
      infarction. RESULTS: Complete reperfusion, defined as normal flow in the right
      main coronary artery and its major right ventricular branches, was achieved in 41
      patients (77 percent), leading to prompt and striking recovery of right
      ventricular function (mean [+/-SE] score for free-wall motion, 3.0+/-0.1 at base
      line and 1.4+/-0.1 at three days; P<0.001). Twelve patients (23 percent) had
      unsuccessful reperfusion, defined as the failure to restore right ventricular
      branch flow, with or without patency of the right main coronary artery.
      Unsuccessful reperfusion was associated with lack of recovery of right
      ventricular function (score for free-wall motion, 3.2+/-0.2 at base line and
      3.0+/-0.9 at three days; P= 0.55), as well as persistent hypotension and low
      cardiac output (in 83 percent of the patients, vs. 12 percent of those with
      successful reperfusion; P=0.002) and a high mortality rate (58 percent, vs. 2
      percent for those with successful reperfusion; P=0.001). CONCLUSIONS: In patients
      with right ventricular infarction, complete reperfusion of the right coronary
      artery by angioplasty results in the dramatic recovery of right ventricular
      performance and an excellent clinical outcome. In contrast, unsuccessful
      reperfusion is associated with impaired recovery of right ventricular function,
      persistent hemodynamic compromise, and a high mortality rate.

PMID- 9521981
TI  - Association between preinfarction angina and a lower risk of right ventricular
      infarction.
AB  - BACKGROUND: Right ventricular infarction occurs in conjunction with inferior
      myocardial infarction caused by proximal occlusion of the right coronary artery.
      However, right ventricular infarction occurs infrequently, and the reasons for
      this are uncertain. METHODS: We retrospectively assessed the association between
      preinfarction angina and right ventricular infarction, as well as the short-term
      outcome, in 113 patients with a first acute inferior myocardial infarction caused
      by right-coronary-artery occlusion. The association between the timing of angina
      during the week before infarction and the clinical outcome was also assessed.
      RESULTS: The absence of preinfarction angina predicted the development of right
      ventricular infarction (odds ratio, 6.3; 95 percent confidence interval, 2.7 to
      15.1; P<0.001), complete atrioventricular block (odds ratio, 3.6; 95 percent
      confidence interval, 1.4 to 10.3; P=0.01), and combined hypotension and shock
      (odds ratio, 12.4; 95 percent confidence interval, 4.5 to 40.6; P<0.001). Angina
      24 to 72 hours before infarction was most strongly associated with reductions in
      the rates of right ventricular infarction (adjusted odds ratio, 0.2; 95 percent
      confidence interval, 0 to 0.8; P=0.02) and combined hypotension and shock
      (adjusted odds ratio, 0.1; 95 percent confidence interval, 0 to 0.5; P=0.02).
      CONCLUSIONS: Preinfarction angina was an independent predictor of the absence of
      right ventricular infarction in patients with acute inferior myocardial
      infarction. The patients with preinfarction angina also had better short-term
      outcomes than those without preinfarction angina.

PMID- 9521982
TI  - Sexual transmission and the natural history of human herpesvirus 8 infection.
AB  - BACKGROUND: Although human herpesvirus 8 (HHV-8) has been suspected to be the
      etiologic agent of Kaposi's sarcoma, little is known about its seroprevalence in
      the population, its modes of transmission, and its natural history. METHODS: The
      San Francisco Men's Health Study, begun in 1984, is a study of a population-based
      sample of men in an area with a high incidence of human immunodeficiency virus
      (HIV) infection. We studied all 400 men infected at base line with HIV and a
      sample of 400 uninfected men. Base-line serum samples were assayed for antibodies
      to HHV-8 latency-associated nuclear antigen (anti-LANA). In addition to the
      seroprevalence and risk factors for anti-LANA seropositivity, we analyzed the
      time to the development of Kaposi's sarcoma. RESULTS: Anti-LANA antibodies were
      found in 223 of 593 men (37.6 percent) who reported any homosexual activity in
      the previous five years and in none of 195 exclusively heterosexual men. Anti
      LANA seropositivity correlated with a history of sexually transmitted diseases
      and had a linear association with the number of male sexual-intercourse partners.
      Among the men who were infected with both HIV and HHV-8 at base line, the 10-year
      probability of Kaposi's sarcoma was 49.6 percent. Base-line anti-LANA
      seropositivity preceded and was independently associated with subsequent Kaposi's
      sarcoma, even after adjustment for CD4 cell counts and the number of homosexual
      partners. CONCLUSIONS: The prevalence of HHV-8 infection is high among homosexual
      men, correlates with the number of homosexual partners, and is temporally and
      independently associated with Kaposi's sarcoma. These observations are further
      evidence that HHV-8 has an etiologic role in Kaposi's sarcoma and is sexually
      transmitted among men.

PMID- 9521983
TI  - Screening of maternal serum for fetal Down's syndrome in the first trimester.
AB  - BACKGROUND: Screening of maternal serum to identify fetuses with Down's syndrome
      is now routinely offered during the second trimester of pregnancy. Prenatal
      screening by means of serum assays or ultrasonographic measurements, either alone
      or in combination, may also be possible in the first trimester. METHODS: We
      measured serum alpha-fetoprotein, unconjugated estriol, human chorionic
      gonadotropin (hCG), the free beta subunit of hCG, and pregnancy-associated
      protein A in 4412 women (82 percent of whom were 35 years of age or older) who
      came to 16 prenatal diagnostic centers for chorionic-villus sampling or early
      amniocentesis at 9 to 15 weeks of gestation. Ultrasound measurements of fetal
      nuchal translucency were also reported. Fetal chromosomal analysis was performed
      in all pregnancies. Altogether, there were 61 fetuses with Down's syndrome.
      RESULTS: A total of 48 pregnancies affected by Down's syndrome and 3169
      unaffected pregnancies were identified before 14 weeks of gestation; the rates of
      detection of Down's syndrome for the five serum markers were as follows: 17
      percent for alpha-fetoprotein, 4 percent for unconjugated estriol, 29 percent for
      hCG, 25 percent for the free beta subunit of hCG, and 42 percent for pregnancy
      associated protein A, at false positive rates of 5 percent. The results of the
      measurements of serum hCG and its free beta subunit were highly correlated. When
      used in combination with the serum concentration of pregnancy-associated protein
      A and maternal age, the detection rate was 63 percent for hCG (95 percent
      confidence interval, 47 to 76 percent) and 60 percent for its free beta subunit
      (95 percent confidence interval, 45 to 74 percent). Measurements of nuchal
      translucency varied considerably between centers and could not be reliably
      incorporated into our calculations. CONCLUSIONS: Screening for Down's syndrome in
      the first trimester is feasible, with use of measurements of pregnancy-associated
      protein A and either hCG or its free beta subunit in maternal serum.

PMID- 9521984
TI  - Bone marrow transplants from unrelated donors for patients with chronic myeloid
      leukemia.
AB  - BACKGROUND: Chronic myeloid leukemia can be cured by marrow transplantation from
      an HLA-identical sibling donor. The use of transplants from unrelated donors is
      an option for the 70 percent of patients without an HLA-identical sibling, but
      the morbidity and mortality associated with such transplants have been cause for
      concern. We analyzed the safety and efficacy of transplants from unrelated donors
      for the treatment of chronic myeloid leukemia and identified variables that
      predict a favorable outcome. METHODS: Between May 1985 and December 1994, 196
      patients with Philadelphia chromosome-positive chronic myeloid leukemia in
      chronic phase received marrow transplants from unrelated donors. RESULTS: The
      median follow-up was 5 years (range, 1.2 to 10.1). Graft failure occurred in 5
      percent of patients who could be evaluated. Acute graft-versus-host disease of
      grade III or IV severity was observed in 35 percent of patients who received HLA
      matched transplants, and the estimated cumulative incidence of relapse at five
      years was 10 percent. The Kaplan-Meier estimate of survival at five years was 57
      percent. Survival was adversely affected by an interval from diagnosis to
      transplantation of one year or more, an HLA-DRB1 mismatch, a high body-weight
      index, and an age of more than 50 years. Survival was improved by the
      prophylactic use of fluconazole and ganciclovir. The Kaplan-Meier estimate of
      survival at five years was 74 percent (95 percent confidence interval, 62 to 86
      percent) for patients who were 50 years of age or younger who received a
      transplant from an HLA-matched donor within one year after diagnosis.
      CONCLUSIONS: Transplantation of marrow from an HLA-matched, unrelated donor is
      safe and effective therapy for selected patients with chronic myeloid leukemia.

PMID- 9521985
TI  - Images in clinical medicine. Chloroma in acute myelogenous leukemia.

PMID- 9521986
TI  - Status epilepticus.

PMID- 9521987
TI  - Reperfusion for right ventricular infarction.

PMID- 9521988
TI  - A chance of cure for every patient with chronic myeloid leukemia?

PMID- 9521989
TI  - Pennsylvania's Focus on Heart Attack--grading the scorecard.

PMID- 9521990
TI  - How large employers are shaping the health care marketplace. First of two parts.

PMID- 9521991
TI  - The unpackaging of routine in older women.
AB  - OBJECTIVE: A qualitative research design using grounded theory procedures and
      techniques was used to explore how routine changed in later adulthood for seven
      Caucasian, college-educated, middle-class women who were not employed and who
      were free of major functional impairments. METHOD: In-depth interviews,
      observations, an autobiography, and researcher-generated memos provided data.
      Data analysis involved concept formation, concept development, and conceptual
      modification and integration. Data collection and analysis were concurrent,
      iterative, reflective, and reflexive. RESULTS: Although the participants used
      routines to facilitate their well-being, they reported doing so to a lesser
      extent than when they had children living at home or when they worked. These
      participants unpackaged routines and molded them into increasingly flexible time
      use strategies in response to age-related changes in their ecocultural niche,
      philosophy of life, and physical status. CONCLUSION: That the participants sought
      less obligation and more freedom as they aged may influence the way they respond
      to a health care practitioner's advocating for an increase in routine.
      Interventions with older women must be compatible with existing routines and
      family themes and directly linked to well-being.

PMID- 9521992
TI  - Clinical interpretation of "the unpackaging of routine in older women".

PMID- 9521993
TI  - Effects of task goal on movement kinematics and line bisection performance in
      adults without disabilities.
AB  - OBJECTIVE: This study investigated (a) whether the kinematic profile of a
      reaching-for-an-object movement would differ depending on the goal of the
      reaching task and (b) the effect of task goal on attentional carryover. METHOD:
      Twenty-four adults without disabilities performed a horizontal line bisection
      task under three conditions: (a) a natural condition (pressing the ringing lever
      of a desk bell), (b) an impoverished condition (touching the ringing lever of a
      desk bell), and (c) a control condition (bisecting a line only). Only the natural
      and impoverished conditions used the reaching task (i.e., pressing or touching
      the ringing lever of the desk bell). The kinematic profile of reaching for the
      bell was established with the OPTO-TRAK system, a quantitative kinematic analysis
      measure. The line bisection task was performed immediately after the reaching
      task, which was located adjacent to the left of the line to be bisected. RESULTS:
      The natural condition elicited better quality of reaching movement than did the
      impoverished condition. It produced significantly shorter movement time and
      higher peak velocity. A less impressive effect was found for percentage of reach
      where peak velocity occurs. Bisection performance under the two experimental
      conditions was leftward biased relative to the control condition, and the
      magnitude of leftward bias in the natural condition was greater than that for the
      impoverished condition. CONCLUSION: Results supported one core assumption of
      occupational therapy: goal-directed and functional tasks can be used to enhance
      human performance. If the results hold for clinical populations, manipulations of
      functional goals may enhance movement performance of persons with disabilities
      and remediate left neglect often seen in clients who have had a stroke.

PMID- 9521994
TI  - Orchestration of work and play within families.
AB  - OBJECTIVES: Parental occupations within families include parents' participation
      in household work and in play with their children. This study explored the nature
      of parents' play with their preschool-aged children and how it was orchestrated
      within their daily occupations. METHOD: Participant observations and intensive
      interviews were conducted with 10 families with preschool-aged children. Data
      were analyzed with a grounded theory approach. RESULTS: Parents used two types of
      strategies to orchestrate work and play in their families: Strategies of
      segregation resulted in play interspersed with household work, and strategies of
      inclusion resulted in play embedded in household work. CONCLUSION: This study
      identified the process of occupational scaffolding through which parents foster
      their children's competence as adults; the need for deconstruction of the notion
      of work and play as separate experiences; and new ideas to guide occupational
      therapy practice with parents who are juggling paid work, household work, and
      time with their children.

PMID- 9521996
TI  - The end of occupational therapy.
AB  - In this article, I propose that the unique end, or goal, of occupational therapy
      is to help persons with performance deficits of any kind make and express meaning
      through organized human performance, which I call occupation. To support this
      thesis, I show that, too often, philosophers, psychologists, and others who have
      studied meaning do not see human performance as a crucial way of making and
      expressing meaning. This article challenges the assumption that meaning making is
      only a cognitive process in which language is its primary expression and shows
      that the nature of humans is to make meaning through occupation. Furthermore,
      this article reveals why occupational therapy should emphasize human performance
      and its role in meaning making. Finally, I propose that occupation is properly
      defined as intentional human performance organized in number and kind to meet the
      demands of self-maintenance and identity in the family and community. I justify
      this definition and discuss the likely therapeutic nature of occupation and
      examples of the end, or goal, of occupational therapy.

PMID- 9521995
TI  - The relationship of cumulative motor asymmetries to scoliosis in Rett syndrome.
AB  - OBJECTIVES: Interrelationships between Rett syndrome scoliosis and symmetric and
      asymmetric motor pull, ambulation, and advancement of age were investigated in
      order to provide a treatment rationale for slowing the progression of scoliosis.
      METHOD: Questionnaires (N = 262) completed by International Rett Syndrome
      Association families were analyzed with logistic regression, odds ratio, Kruskal
      Wallis one-way, and Fisher's exact test analyses. RESULTS: Rett syndrome
      scoliosis was found to be significantly related to orthopedic risk factors of
      asymmetric movements and positions (odds ratio = 4.5, p < .001). The odds ratio
      for asymmetric upper-body positioning (4.4), nonambulation (3.1), and age
      advancement (14.1) indicated that each was a significant predictor of scoliosis
      by logistic regression analysis. Univariate Kruskal-Wallis one-way analysis
      identified a significant relationship between scoliosis and asymmetric higher
      shoulder positioning (p < .001) and bodyside movements (p = .03). Hemisyndrome
      aspects of Rett syndrome were identified as the increased prevalence of symptoms
      in either right or left bodyside. CONCLUSION: A significant relationship was
      found between the prevalence of Rett syndrome scoliosis and orthopedic risk
      factors. These findings suggest a treatment approach for Rett syndrome scoliosis
      that focuses on balancing bilateral muscular pull.

PMID- 9521997
TI  - Use of a computer simulator for training children with disabilities in the
      operation of a powered wheelchair.
AB  - OBJECTIVE: The purpose of this study was to evaluate the ability of a basic
      driving simulator program to evaluate and train children with disabilities in
      their ability to operate a powered wheelchair. METHOD: With a rating scale of
      skills considered essential for safe and efficient wheelchair operation, 22
      children 7 to 22 years of age with either progressive muscular dystrophy or
      cerebral palsy were evaluated in their ability to drive a powered wheelchair
      through a driving course. They were divided into two groups: one without prior
      experience driving a powered wheelchair and the other with experience. After the
      driving assessment with an actual powered wheelchair, the inexperienced drivers
      were trained on a joystick-controlled computer game in which they navigated
      through labyrinths similar in layout to their own school environment. A test maze
      was administered before and after this training. Both groups were then evaluated
      on their ability to drive a powered wheelchair through the driving course.
      RESULTS: The inexperienced drivers significantly increased their simulator scores
      over the training period. Their wheelchair driving performance was significantly
      better after the simulator training, although their performance remained poorer
      than that of the experienced drivers. CONCLUSION: A simulator program can assist
      in the development and evaluation of the skills required to operate a powered
      wheelchair.

PMID- 9521998
TI  - Teaching clinical reasoning as a thinking frame.
AB  - OBJECTIVE: Clinical reasoning concepts can be viewed as descriptions of mental
      operations or as a thinking frame--a structure to organize and support clinical
      thinking. This study examined an approach for teaching clinical reasoning as a
      thinking frame to occupational therapy students. METHOD: A quasi-experimental,
      pretest-posttest design was used with a convenience sample of 10 undergraduate
      occupational therapy seniors. All participants (a) acquired the thinking frame of
      clinical reasoning concepts through explicit instruction and (b) practiced that
      thinking frame with an external aid--the Clinical Reasoning Case Study Format.
      The accuracy of participants' definitions of clinical reasoning concepts before
      and after this learning experience were examined to assess their acquisition of
      the thinking frame. The content of clinical reasoning case studies were examined
      to assess students' application of the thinking frame to clinical situations.
      RESULTS: Wilcoxon signed rank tests done on presemester and postsemester
      definitions ratings indicated that the latter were rated significantly higher
      than the former for (a) narrative reasoning (p = .008), (b) procedural reasoning
      (p = .005), (c) interactive reasoning (p = .006), (d) pragmatic reasoning (p =
      .008), and (e) conditional reasoning (p = .01). The content of participants'
      clinical reasoning case studies indicated that they were able to apply clinical
      reasoning concepts. CONCLUSION: The results suggest that using a clinical
      reasoning thinking frame to organize clinical observations is an effective way to
      help entry-level occupational therapy students learn and apply clinical reasoning
      concepts.

PMID- 9521999
TI  - Skills for teaching: a problem-based learning faculty development workshop.

PMID- 9522000
TI  - Why are occupational therapists not doing more replication research?

PMID- 9522001
TI  - Diagnosis of personality disorders in cocaine-dependent individuals.
AB  - The authors explored the relationship between personality disorder (PD) and
      cocaine use. Diagnostic interviews for PD were performed at baseline and 12 weeks
      (study termination) in 47 cocaine-dependent individuals entering a pharmacologic
      treatment trial; 68% met criteria for a PD at baseline, 51% at study termination.
      In comparing baseline and termination PD, 22 individuals had no change in the
      number of PDs, 6 had more, and 17 had fewer. The group with an increase in the
      number of PD diagnoses had more positive urine drug screens than either of the
      other groups and more cocaine use by self-report. Personality disorders appear to
      be common in cocaine-dependent individuals but may be affected by cocaine use and
      withdrawal.

PMID- 9522002
TI  - Use of the Internet for addiction education. Combining network therapy with
      pharmacotherapy.
AB  - The authors prepared a course in addiction psychiatry for the Internet that
      combines a psychosocial and a medication modality for alcoholism; namely, network
      therapy and naltrexone. Responses of those who accessed the course revealed 679
      counts (visits) at the Web Site. A group of 210 unique respondents, of whom 154
      were psychiatrists, answered a demographic question set. Over half of these
      psychiatrists completed the course and evaluated it. The majority indicated that
      it helped them understand "a good deal" about the management of alcoholism and
      the use of network therapy and naltrexone. This result suggests the feasibility
      of using the Internet as a vehicle for teaching in addiction psychiatry, an area
      where needs for training are often unmet.

PMID- 9522003
TI  - Further validation of the Obsessive-Compulsive Drinking Scale (OCDS).
      Relationship to alcoholism severity.
AB  - The authors administered the Obsessive-Compulsive Drinking Scale (OCDS), a self
      rated questionnaire that quantifies some cognitive and behavioral dimensions of
      "craving" for alcohol, to 124 alcohol-dependent subjects in three pharmacological
      treatment studies. The OCDS total scores had significant correlations with both
      the Alcohol Dependence Scale (r = 0.42; P < 0.0001) and the alcohol subscale of
      the Addiction Severity Index (r = 0.44; P < 0.0001). Previous alcoholism
      treatment was associated with higher OCDS Total and Obsessive subscale scores.
      These data support the congruent validity of the OCDS with previously well
      established measures of alcohol dependence severity and suggest that this
      measurement of craving may help in formulating appropriate treatment plans for
      alcoholic patients.

PMID- 9522004
TI  - The Minnesota Substance Abuse Problems Scale. Psychometric analysis and
      validation in a clinical population.
AB  - The authors determined interrelationships among 61 items in a scale designed to
      assess the severity of substance-related disorder (SRD) and develop subscales
      that measure distinct substance-related areas of dysfunction. They evaluated 642
      outpatients with items previously developed among patients with SRDs. Trained
      interviewers administered the Minnesota Substance Abuse Problem Scales (M-SAPS),
      which uses responses to yes/no (lifetime) questions. A factor analysis of items
      was compared with data from patients and addiction psychiatrists to measure the
      concurrent validity of the M-SAPS factors, yielding 37 items in three factors:
      Psychiatric-Behavioral Problems (14 items), Social-Interpersonal Problems (11
      items), and Addiction-Dependence Symptoms (12 items). These three scales
      correlate with 10 scales/assessments concurrently collected independently of the
      M-SAPS, yielding a brief, valid, interviewer-administered, substance-related
      problem scale that assesses SRD severity in three distinct areas.

PMID- 9522005
TI  - Drug use problem awareness and treatment readiness in dual-diagnosis patients.
AB  - Problem awareness and treatment readiness are factors that influence treatment
      seeking behavior, and thus, morbidity and outcome. The authors elucidated
      patterns of problem awareness and treatment readiness among hospitalized dually
      diagnosed patients by administering the Problem Awareness and Readiness for
      Treatment subscales of the Alcohol Use Inventory to 67 psychiatric inpatients
      with comorbid substance-related disorders and using a multivariate model approach
      to data analysis. The results suggested differential and interactive effects of
      gender, ethnicity, voluntary admission status, and a diagnosis of major
      depression (MDD) on drug abuse problem awareness and treatment readiness. Female
      gender, voluntary admission status, and a comorbid diagnosis of MDD were
      associated with increased awareness and readiness for treatment.

PMID- 9522006
TI  - Treatment needs and initial outcomes of a residential recovery program for
      African-American women and their children.
AB  - The current research was designed to assess the treatment needs of 42 substance
      abusing women and the efficacy of a women-based, culturally influenced,
      multifaceted residential treatment program for women and their children. Women
      presented with multidimensional treatment needs, including limited
      educational/employment histories, significant child-care needs, and histories of
      victimization and psychological distress. Women remained in residence for an
      average of 259 days. In all, 88% of the women remained substance-free at
      discharge; 49% had jobs or were enrolled in school/job training. This integrated,
      gender/culture-based approach provides a model for more effective substance-abuse
      treatment for women and their families.

PMID- 9522007
TI  - Substance use disorders in gay/bisexual men with HIV and AIDS.
AB  - The authors conducted a longitudinal study of psychological adaptation to AIDS in
      subjects with and without lifetime and current substance use disorders (SUD), in
      a cohort of HIV+ gay/bisexual subjects. A sample of HIV+ gay/bisexual men (n =
      183) and an HIV- comparison group (n = 84) were assessed for SUD, depression, and
      anxiety disorders. Among HIV+ men, combined lifetime (42%) but not current
      (11.5%) SUDs were more prevalent than in HIV- men (27% and 10%, respectively).
      HIV+ men with current SUD reported more depression, distress and diminished
      quality of life than HIV+ men with no SUD, but HIV-illness severity did not
      differ. HIV+ men in recovery did not differ from men with no lifetime history.
      Most HIV+ gay/bisexual men with SUD discontinue or reduce substance use before or
      subsequent to knowledge of their HIV infection, probably in an attempt to adopt a
      healthier lifestyle. However, for some HIV+ men, persistent substance
      abuse/dependence is accompanied by higher levels of distress and diminished
      quality of life, underscoring their need for treatment intervention.

PMID- 9522008
TI  - The role of multifamily therapy in promoting retention in treatment of alcohol
      and cocaine dependence.
AB  - The authors present a model for incorporating multifamily therapy in the
      treatment of chemical dependency and investigate the association of family
      participation in multifamily therapy group with treatment retention in a sample
      of 164 alcohol- and/or cocaine-dependent outpatients. Results indicate that level
      of family attendance at a multifamily group strongly predicted completion of
      short-term and long-term out-patient treatment. Effects were greater for cocaine
      dependent than for alcohol-dependent subjects in analyses of short-term treatment
      retention. Multifamily therapy may be a powerful method to engage patients
      families in treatment and promote treatment retention, especially in the early,
      intensive phases of treatment for cocaine dependency.

PMID- 9522009
TI  - HIV risk factors in dually diagnosed patients.
AB  - The authors examined correlates of HIV seropositivity in a sample of dually
      diagnosed inpatients. The subjects were 147 consecutively admitted patients to a
      specialized dual-diagnosis unit in a municipal hospital who were given a
      structured interview and HIV testing. The HIV seroprevalence was 19%, with women
      having a nearly fourfold increased risk of being HIV seropositive, as compared
      with men. Cocaine as drug of choice was also highly significant as a risk factor
      for HIV infection, independent of gender. This finding suggests that targeted
      prevention and education programs need to be developed for the dually diagnosed
      patient.

PMID- 9522010
TI  - Psychiatric hospital outcomes of dual diagnosis patients under managed care.
AB  - The authors compared patterns of psychiatric hospitalization utilization and
      outcomes between persons with and without co-existing substance-related disorders
      in a managed care environment by means of a prospective follow-along study of
      persons hospitalized for psychiatric reasons under the auspices of a large
      regional managed care firm. Forty-two psychiatric inpatients with comorbid
      substance disorders and 121 inpatients without coexisting substance disorders
      were compared across measures of service use and psychiatric acuity. Readmission
      to the hospital was assessed at 30 days and after 6 months. Patients with
      coexisting substance disorders spent fewer days in the hospital, but were
      rehospitalized at a higher rate both within 30 days and (significantly) after 6
      months. These results suggest that the revolving-door pattern of service
      utilization is also present in managed care environments.

PMID- 9522011
TI  - Observations on treatment with ibogaine.

PMID- 9522012
TI  - Risperidone, ERG and cocaine craving.

PMID- 9522013
TI  - [Evidence-based medicine].

PMID- 9522014
TI  - [Solitary pulmonary nodule: application of Bayes theorem in prediction of
      malignancy].
AB  - Most radiological signs are of low specificity for predicting malignancy in
      patients with a solitary pulmonary nodule (SPN), making clinical management
      difficult. Only certain calcification patterns in SPN or the absence of growth
      over a period two years assures that the nodule is benign. The clinical and
      radiological characteristics of 31 patients with SPN were studied. Twenty-two
      were cases bronchopulmonary carcinoma and 9 were pulmonary tuberculoma. Accuracy
      in the prediction of malignancy was assessed using Bayes' theorem, which is based
      on degrees of likelihood of various radiological and clinical characteristics.
      Patients with carcinoma (mean age 65 +/- 9 years) were significantly older than
      those with tuberculoma (38 +/- 19 years) (p < 0.05). The proportion of smokers
      was significantly higher among patients with carcinoma (91%) than those with
      tuberculoma (44%) (p < 0.05). In 50% of the patients with SPN due to
      bronchopulmonary carcinoma (11 patients), the nodule was in the upper right lobe;
      in 55% of those with tuberculomas (5 patients) the nodule was found in the upper
      left lobe. There were no significant differences in the characteristics of the
      computerized tomography images for the two groups. Mean likelihood of malignancy
      for patients with carcinoma, by Bayes' theorem, was 83.7%, a rate that was
      significantly higher than that of tuberculoma patients (46%) (p < 0.05). The
      application of Bayes' probability theorem for a set of clinical and radiological
      characteristics can orient the physician as to whether an SPN is likely to be
      malignant or not, thereby providing guidance on the advisability of performing
      invasive diagnostic procedures to determine etiology.

PMID- 9522015
TI  - [Follow-up of patients with non-small-cell pulmonary cancer undergoing complete
      resection. Should surgeons be in charge?].
AB  - To evaluate the effectiveness of patient follow-up after complete lung resection
      for non-small cell carcinoma in the same unit where the patients were treated.
      Retrospective review of outpatient clinic records of patients undergoing surgery
      for lung cancer between January 1994 and December 1996 who met the following
      conditions: histologically complete resection (segmentary and wedge resections
      were excluded) and survival at least three months after surgery. Follow-up was in
      accordance with preestablished guidelines that included taking the patient's
      medical history and performing physical examination, simple chest X-ray,
      hematocrit and biochemical parameters, chest and abdominal computerized
      tomography (CT) and periodic bronchoscopy. In 103 cases followed for between
      three to 34 months, 27 recurrences were detected (13 remote, 11 local and 3 local
      and remote). The clinical diagnosis of recurrence was made by case history adn
      physical examination in 18 cases, by simple chest film in 3, by biochemical blood
      parameters in 2, by fiber optic bronchoscopy in 2, and by CT findings in 2. One
      of the patients with local recurrence (bronchial stump) underwent a second
      operation 11 months after the first. Most recurrences are detected during simple
      checkups that can be performed without hospital admission. Only one patient
      underwent surgery for a local recurrence, suggesting that follow-up by thoracic
      surgery units does not appear to be worthwhile.

PMID- 9522016
TI  - [Approach to bronchopleural fistula in patients undergoing lung cancer surgery. A
      prospective study].
AB  - Twenty-four cases of bronchopleural fistula were found by fiberoptic bronchoscopy
      performed in 526 consecutive patients undergoing surgery for diagnosis or
      treatment of lung cancer between February 1990 and January 1997 in Hospital
      General Universitario in Valencia (Spain). In 327 of the patients lung resection
      was performed. Clinical symptoms included fever, purulent or bloodstained
      expectoration, chest pain, dyspnea and general unfitness, with 83.33% of the
      patients having pleural empyema. Treatment was based on pleural drainage and
      broad-spectrum antibiotic therapy, along with planning of the appropriate surgery
      technique to each patient. Surgery consisted in re-thoracotomy and bronchial
      closure in early detection cases without evidence of infection (< 48 h);
      thoracostomy (Clagett) and second stage myoplasty if confirmed pleural infection;
      thoracoplasty in cases of incomplete fistulas that were unresolved by pleural
      drainage. Biological glues were delivered by fiberoptic bronchoscope in one
      patient. The incidence of bronchopleural fistula was studied, as were associated
      factors and the results obtained by various surgical techniques.

PMID- 9522017
TI  - [Usefulness of mucoactive drugs in respiratory diseases].

PMID- 9522019
TI  - [Several aspects of Mantoux test].

PMID- 9522018
TI  - [Pulmonary sequestration: 2 cases (intralobar and extralobar) in surgically
      treated adults].
AB  - We present two cases of pulmonary sequestration, one intralobar and the other
      extrapulmonary, in young adults. The diagnoses were obtained after surgical
      resection in both cases. The cases are of interest in that the first (intralobar
      sequestration) started with massive hemoptysis requiring emergency treatment, and
      the second (extrapulmonary sequestration) involved an unusual location in the
      upper mediastinum, requiring surgery by video assisted thoracoscopy.

PMID- 9522020
TI  - [Breast tumor as presentation of pleural tuberculosis].

PMID- 9522021
TI  - [Intestinal metastasis of bronchogenic carcinoma].

PMID- 9522022
TI  - [Cerebrospinal fluid fistula and thoracic trauma].

PMID- 9522024
TI  - [The relative bioavailability and pharmacokinetics of chloral hydrate and its
      metabolites].
AB  - Two open, randomized cross-over trials were performed in 18 healthy volunteers
      each to evaluate the relative bioavailability and the pharmacokinetics of chloral
      hydrate (CAS 302-17-0), the active ingredient of Chloraldurat 500 (immediate
      release capsules, CH), Chloraldurat rot (immediate release capsules, CR) and
      Chloraldurat blau (enteric-coated modified release capsules, CB). In the first
      study the male subjects, aged 21 to 31 years, were randomly given one capsule of
      CH or 500 mg of chloral hydrate as drinking solution. In the second study the
      volunteers, aged 20 to 28 years, received either one capsule of CR or one capsule
      of CB or 250 mg of chloral hydrate as drinking solution. The time of
      administration was between 6:30 and 7:30 a.m. and the capsules had to be
      swallowed with 150 ml water. The reference medication consisted of 150 ml
      drinking solution. The wash out time in both studies was 4 weeks. Prior to the
      administration and (2, 4, 6, only for CH) 8, 10, 15, 20, 40, 60 min and 1.5, 2,
      4, 6, 8, 12, 24, 36, 48, 72, 96, 144, 192, 240 (and 408 only for CR/CB) h
      afterwards blood samples of 4.5 ml were taken from the antecubital vein.
      Additional 4.5 ml were drawn before and 10, 20, 40 and 60 min after
      administration to detect unchanged chloral hydrate. In the second study times of
      blood sampling were modified up to 4 h after administration due to the estimated
      later onset of release from CB in comparison to CR. Blood samples were
      centrifuged within 20 min, the plasma was separated and immediately frozen at -20
      degrees C. Due to the extremely short terminal half-life of chloral hydrate its
      active metabolite trichloroethanol is regarded as the pharmacokinetically
      relevant parameter for the assessment of the bioavailability of the parent
      substance. Compared to the reference formulation (drinking solution) the
      bioavailability of trichloroethanol was 94.8% (CH), 100.7% (CR) and 101.6 (CB),
      respectively. The maximum plasma concentrations (Cmax) of trichloroethanol were
      5176 ng/ml after intake of CH (reference 6131 ng/ml), after intake of CR 3241
      ng/ml and CB 3279 ng/ml (reference 2993 ng/ml). Maximum plasma concentrations
      (tmax) of trichloroethanol were reached after 0.67 h (reference) and after 0.98
      (CH), 0.76 (CR) and 2.38 h (CB), respectively. The terminal half-life for
      trichloroethanol was calculated to be 9.3 to 10.2 h, for the inactive metabolite
      trichloracetic acid the half-life ranged from 89 to 94 h. Chloral hydrate itself
      could be detected only 8 to 60 min after application at very low concentrations
      in some of the plasma samples. It is justified to characterize its
      bioavailability by the active metabolite trichloroethanol due to the extremely
      short terminal half-life and high variability of the parent substance.

PMID- 9522023
TI  - [The plasma level of the neurotoxin 1-trichloromethyl-1,2,4,5-tetrahydro-beta
      carboline (TaClo) in man after oral administration of chloral hydrate].
AB  - Chloral hydrate (CAS 302-17-0) is a widely used hypnotic and sedative agent. It
      was recently reported in the literature that a neurotoxin, TaClo (1
      trichloromethyl-1,2,3,4-tetrahydro-beta-carboline), may be formed in vitro from
      tryptamine (Ta) and chloral (Clo). Intraperitoneal administration of TaClo led to
      parkinson-like symptoms in the rat. Hence, the plasma levels of TaClo were
      determined at various time-points in 18 healthy volunteers in two periods each
      during a bioavailability study of several chloral hydrate preparations. The limit
      of quantitation for TaClo was 5 ng/ml. No TaClo could be determined in the plasma
      of the various volunteers following administration of human therapeutic doses of
      chloral hydrate. Hence, it is unlikely that TaClo will be formed in man after
      application of therapeutic doses of chloral hydrate to patients.

PMID- 9522025
TI  - Cardioprotective effects of dihydrolipoic acid and tocopherol in right heart
      hypertrophy during oxidative stress.
AB  - Rat hearts hypertrophied by exposure of the animals to low oxygen pressure were
      perfused by the Langendorff technique. After oxidative stress induced by
      hypoxia/reoxygenation, functional recovery of the hypertrophied right heart was
      insufficient when compared to non-hypertrophied controls. Accordingly,
      mitochondrial membrane potential did not recover sufficiently. There was a
      positive trend for improvement of the rate-pressure product during reoxygenation
      in lipoic acid (CAS 1077-28-7; 0.8 mumol/l) treated hearts which was also
      verified for membrane potential. Adenosine 5'-triphosphate and creatine phosphate
      contents as well as the ATP/ADP ratio in hypertrophied right ventricle were
      significantly increased after reoxygenation in hearts treated with lipoic acid.
      With lipoic acid, there was a significantly higher content of glutathione
      (oxidized form) after reoxygenation, Ca2+ uptake was significantly increased in
      mitochondria isolated from hypertrophied right ventricles and treated by 12
      nmol/mg protein of lipoic acid. The results reveal a distinct improvement of
      mitochondrial structure/function by lipoic acid and suggest for therapy a
      combination with the synergistic free radical scavenging properties of tocopherol
      (CAS 10191-41-0).

PMID- 9522026
TI  - Vasorelaxant and negative inotropic effects of gallopamil and LU49700, a
      metabolite of gallopamil, on isolated rat aorta and guinea-pig ventricular
      myocardium.
AB  - The effects of LU49700 (CAS 116759-60-5), the main metabolite of gallopamil (CAS
      16662-47-8) on the mechanical response of isolated rat aortic and guinea-pig
      ventricular papillary muscle preparations were compared with those of gallopamil.
      Gallopamil and LU49700 inhibited the 64 mmol/l KCl-induced contraction of rat
      aorta in a concentration-dependent manner. The vasorelaxant potency of LU49700
      was 244 times weaker than that of gallopamil. Gallopamil and LU49700 produced
      concentration-dependent negative inotropic effects on isolated right ventricular
      papillary muscles. The negative inotropic potency of LU49700 was 418 times weaker
      than that of gallopamil. These findings indicate that LU49700 has a weaker
      cardiovascular depressant potency than gallopamil. Therefore, LU49700 may not
      mediate the effects of gallopamil for treating subjects with cardiovascular
      diseases.

PMID- 9522027
TI  - Effect of heart rate reduction by 4-(N-ethyl-N-phenyl-amino)-1,2-dimethyl-6
      (methylamino)pyrimidinium chloride on infarct size in dog.
AB  - Heart rate (HR) reduction may reduce the severity of myocardial ischemia. ZD7288
      (4-(N-ethyl-N-phenylamino)-1,2-dimethyl-6-(methylamino)pyrimidinium++ + chloride)
      is a novel bradycardic agent with a specific effect on the sinoatrial node
      without having any other direct effects on the heart. In the present study, the
      effect of ZD7288 on infarct size and regional myocardial function during regional
      myocardial ischemia and reperfusion was investigated. Seventeen anesthetized open
      chest dogs (control, n = 8, and ZD7288, n = 9) underwent 1 h of left anterior
      descendent artery (LAD) occlusion followed by 6 h of reperfusion. In one group,
      ZD7288 was given intravenously (0.7 mg/kg body weight) 45 min before LAD
      occlusion. Regional myocardial function was assessed by sonomicrometry as
      systolic wall thickening fraction (sWTF) in the anteroapical (interest region,
      IR) and the posterobasal wall (control region, CR). Ischemic regional myocardial
      blood flow (RMBF) was determined by colored microspheres and infarct size (IS) by
      triphenyltetrazolium staining. ZD7288 injection decreased HR from 104 +/- 5 to 74
      +/- 3 bpm (mean +/- SEM, p < 0.001 vs control, vs baseline), but did not change
      sWTF. During reperfusion, sWTF of the IR was significantly greater in the ZD7288
      group (26 +/- 12 vs -14 +/- 13%, 1 h reperfusion, p < 0.05), while sWTF of CR
      stayed equal (120 +/- 13 vs 111 +/- 16%, p = ns). IS was markedly reduced in the
      ZD7288 group (4.7 +/- 1.8 vs 18.0 +/- 5.2% of IR, p < 0.05). There was no
      difference in ischemic endocardial RMBF (ZD7288 11.0 +/- 4.3 vs control 12.3 +/-
      6.5 ml/min/100 g, p = ns). ZD7288 reduces HR without having direct effects on
      regional myocardial function. This HR reduction leads to a smaller IS and to a
      better regional functional recovery.

PMID- 9522029
TI  - Quantitative structure-activity relationship study of some 7-substituted
      theophyllines.
AB  - Some novel 7-substituted theophylline derivatives have been investigated for
      quantitative structure-activity relationship (QSAR). For this purpose, their
      bronchodilatory activities (in vitro), which were examined by the inhibition of
      acetylcholine induced contraction in tracheae isolated from guinea pigs, have
      been correlated with various quantum chemical and physicochemical parameters.

PMID- 9522028
TI  - Metabolism of 14C-moxisylyte after percutaneous application in hairless rat.
AB  - The pharmacokinetics of 14C-thymoxamine (4-(2-dimethylaminoethoxy)-5-isopropyl-2
      methyl phenyl acetate, CAS 54-32-0, moxisylyte, Carlytene) were studied in female
      hairless rats following different administration routes: oral, intravenous or
      percutaneous. After percutaneous administration, the half-life of elimination of
      14C-thymoxamine and its metabolites was longer (t 1/2 = 15 h) than after oral or
      intravenous administration (t 1/2 = 9 h). The penetration/resorption phenomenon
      of thymoxamine base mainly located in the horny layer could explain the high
      value of the pseudo half-life of elimination observed after percutaneous
      administration. Due to the absorption slower than elimination, this special
      pharmacokinetics had to be considered as a flip-flop model. The type and
      proportions of thymoxamine metabolites recovered in plasma varied according to
      the route of administration. The unconjugated metabolites, desacetyl-thymoxamine
      (DAT) + desacetyl-desmethyl-thymoxamine (DMAT), were observed only after
      intravenous or percutaneous administration, they represented 12% and 15%,
      respectively. They were never observed after oral administration suggesting the
      existence of a hepatic first-pass metabolism. The other metabolites observed were
      sulphate conjugates and glucuronides of DAT + DMAT. The values of sulfoconjugates
      were constant with each administration route (21%), whereas glucuronides
      increased with oral administration. In conclusion, the pharmacokinetics of
      percutaneous thymoxamine presented two main features: the drug absorption was
      high and durable (t 1/2 = 15 h); the cutaneous application allowed to avoid the
      hepatic first-pass metabolism.

PMID- 9522030
TI  - Inhibitory effect of oxatomide on oxygen-radical generation and peptide
      leukotriene release from guinea pig eosinophils.
AB  - Eosinophils are prominent inflammatory cells which play a critical role in the
      pathogenesis of allergic diseases and bronchial asthma. The aim of this
      experiment was to examine the effects of oxatomide (CAS 60607-34-3, KW-4354), an
      antiallergic agent, on oxygen-radical generation and peptide-leukotriene (p-LT)
      release from guinea pig eosinophils. Ketotifen (CAS 345080-13-7) and epinastine
      (CAS 80012-43-7) were used as reference drugs. Eosinophils were isolated from the
      peritoneal exudate of guinea pigs, in which peritoneal eosinophilia had been
      induced by injection of horse serum. Oxygen-radicals were measured with luminol
      dependent chemiluminescence and p-LT release was measured with enzyme
      immunoassay. When eosinophils were stimulated with phorbol miristate acetate,
      oxatomide and ketotifen inhibited the oxygen-radical generation with a
      concentration required for 50% inhibition (IC50) of 11.7 mumol/l and 28.4
      mumol/l. Oxatomide, ketotifen or epinastine showed an inhibition of oxygen
      radical generation induced by calcium ionophore A-23187 and the IC50 value was
      11.3 mumol/l for oxatomide, 15.1 mumol/l for ketotifen and 27.3 mumol/l for
      epinastine, suggesting that oxatomide is a more potent inhibitor of oxygen
      radical generation than ketotifen and epinastine. Oxatomide also inhibited p-LT
      release induced by calcium ionophore A-23187 (IC50, 9.83 mumol/l). Ketotifen and
      epinastine only weakly inhibited p-LT release. These results suggest that
      oxatomide may regulate inflammatory diseases, such as bronchial asthma, through
      suppression of eosinophil function.

PMID- 9522031
TI  - Effects of prostaglandin E2 on nitric oxide-mediated nonadrenergic noncholinergic
      relaxations in the guinea-pig tracheal muscle.
AB  - The effects of histamine, prostaglandin (PG) E2 and substance P (SP) on functions
      of nonadrenergic noncholinergic inhibitory (iNANC) nerves were examined in the
      guinea-pig tracheal muscle in vitro. In the presence of indometacin (10 mumol/l),
      atropine (2 mumol/l) and propranolol (1 mumol/l), field stimulation (FS) (1-80
      Hz, 1 ms, 30 V for 45 s) was applied to the muscle strip under a condition where
      the same degree of contraction was produced by each agonist. Magnitudes of FS
      induced relaxations were significantly smaller for the case of PGE2- or SP
      produced contraction than those for the case of histamine-produced contraction.
      The FS-induced relaxations at lower stimulus frequencies (1-5 Hz) were suppressed
      by N omega-nitro-L-arginine methylester (L-NAME) (100 mumol/l) during histamine,
      although they were not affected by L-NAME during PGE2 or SP. Susceptibility of
      tracheal muscle to S-nitroso-N-acetylpenicillamine, a donor of nitric oxide (NO),
      was not different during PGE2 or histamine; it was significantly less during SP.
      FS-induced relaxation during histamine was suppressed by concomitant
      administration of PGE2 (10 nmol/l), however, not by concomitant administration of
      SP (30-100 nmol/l). These results suggest that PGE2 may inhibit release of NO
      from iNANC nerves in airways, whereas SP may suppress responsiveness of airway
      smooth muscle to the released NO. Results also indicate a possible involvement of
      these inflammatory mediators under conditions where airway iNANC nerves are
      impaired.

PMID- 9522032
TI  - Effects of loxiglumide on pancreatic exocrine secretion stimulated by
      cholecystokinin-8 in conscious dogs.
AB  - The effects of loxiglumide (CAS 107097-80-3, CR 1505), a novel cholecystokinin
      A(CCK-A) receptor antagonist, on pancreatic exocrine secretion stimulated by
      exogenously administered CCK-8 were examined in conscious dogs with chronic
      pancreatic fistula. Pancreatic exocrine secretion in dogs was significantly
      increased by intravenous infusion of CCK-8 at a dose of 0.06 microgram/kg/h.
      Loxiglumide inhibited CCK-8-augmented outputs of pancreatic protein, trypsin and
      amylase at intravenous doses of 1, 3, 10 mg/kg/h (p < 0.05 or 0.01), and
      inhibited pancreatic juice volume at a dose of 10 mg/kg/h (p < 0.05). These
      results demonstrated that the selective CCK-A antagonist loxiglumide inhibited
      the increase of pancreatic exocrine secretion stimulated by CCK-8 based on
      selective blockade of receptor binding of CCK in dogs.

PMID- 9522033
TI  - Effects of loxiglumide on pancreatic exocrine secretion stimulated by meal in
      conscious dogs.
AB  - The effects of loxiglumide (CAS 107097-80-3, CR 1505), a novel cholecystokinin
      A(CCK-A) receptor antagonist, on pancreatic exocrine secretion stimulated by meal
      were examined in conscious dogs with chronic pancreatic fistula. Pancreatic
      exocrine secretion was stimulated by intraduodenal infusion of a liquid test meal
      and postprandial plasma CCK levels were apparently elevated. Loxiglumide
      inhibited the meal-stimulated outputs of pancreatic protein, amylase and
      bicarbonate at an intravenous dose of 10 mg/kg/h (p < 0.05). However, loxiglumide
      did not show apparent inhibition of pancreatic juice volume and trypsin output.
      These results show that the selective CCK-A antagonist loxiglumide may inhibit
      the increase of pancreatic exocrine secretion based on selective blockade of
      receptor binding of CCK endogenously induced by meal in dogs.

PMID- 9522034
TI  - Biochemical and pharmacological profiles of loxiglumide, a novel cholecystokinin
      A receptor antagonist.
AB  - Loxiglumide ((+/-)-4-(3,4-dichlorobenzamido)-N-(3-methoxypropyl)-N-
      pentylglutaramic acid, CAS 107097-80-3, CR1505) is a new derivative of glutaramic
      acid. Radioligand displacement assay was performed to characterize the
      selectivity of loxiglumide to CCK-A (cholecystokinin-A) receptor (rat pancreas
      and bovine gallbladder) and CCK-B/gastrin receptors (guinea pig cerebral cortex
      and guinea pig gastric parietal cell). And tissue bioassay was performed to
      investigate the effect of the compound on contractions of the guinea pig
      gallbladder and ileum. Loxiglumide inhibited 125I-CCK-8 binding to rat pancreatic
      and bovine gallbladder membranes with IC50 values of 195 and 77.1 nmol/l,
      respectively. Loxiglumide also inhibited 125I-CCK-8 binding to guinea pig
      cerebral cortex membranes and parietal cells with IC50 values of 12363 and 15455
      nmol/l, respectively. In addition, loxiglumide inhibited 125I-gastrin binding to
      guinea pig parietal cells with IC50 values of 6134 nmol/l. These results indicate
      that the affinity of loxiglumide to CCK-A receptor is at least 63 times greater
      than that to CCK-B/gastrin receptors. In vitro functional studies utilizing CCK
      induced contractions of the isolated guinea pig gallbladder and ileum further
      demonstrate that loxiglumide acts as a competitive CCK antagonist with a high
      affinity to these tissues (gallbladder, pA2:6.71).

PMID- 9522035
TI  - Effects of loxiglumide on experimental acute pancreatitis in comparison with
      gabexate mesilate.
AB  - Loxiglumide ((+/-)-4-(3,4-dichlorobenzamido)-N-(3-methoxypropyl)-N-
      pentylglutaramic acid, CAS 107097-80-3, CR 1505) is a cholecystokinin-A (CCK-A)
      receptor antagonist. In this report, the effects of loxiglumide and gabexate
      mesilate were studied on three experimental acute pancreatitis models induced by
      caerulein, sodium taurocholate + caerulein and closed duodenal loop. The
      intravenous injection of loxiglumide at 3 and 10 mg/kg (6 times at hourly
      intervals) significantly inhibited an increase in serum amylase activity induced
      by the intraperitoneal injection of caerulein (50 micrograms/kg i.p., 6 times at
      hourly intervals) in mice. But gabexate mesilate at 10, 30 and 60 mg/kg did not.
      The intravenous infusion of loxiglumide at 18 and 60 mg/kg/h showed a life
      prolonging effect in the lethal necrotizing pancreatitis, induced by the
      subcutaneous injection of caerulein (50 micrograms/kg s.c., 4 times at 2 h
      intervals) after the injection of sodium taurocholate (10%, 0.1 ml/body) into the
      common bile duct, cumulative survival rates being 86 and 90%, respectively.
      Gabexate mesilate at 180 mg/kg/h showed the prolonging effect (cumulative
      survival rates 75%). The intravenous injection of loxiglumide at 6, 18 and 60
      mg/kg/h significantly inhibited an increase in total ascitic lipase activity, and
      plasma amylase and lipase activity of rats with closed duodenal loop. These
      results suggest that CCK plays an important role in the progression of acute
      pancreatitis, and that loxiglumide may have a therapeutic potential for
      pancreatitis.

PMID- 9522036
TI  - Gastric mucosal function following withdrawal of omeprazole in rats.
AB  - In the following study the function of gastric mucosa after withdrawal of 4-week
      suppression of acid secretion was examined. Rats were treated orally for 4 weeks
      with omeprazole (CAS 73590-58-6, 150 mg/kg/day). While elevated plasma gastrin
      levels during the treatment returned to normal 4 days after the last dosing,
      exogenously applied pentagastrin induced higher acid secretion compared with the
      vehicle-treated controls. Acetylsalicylic acid induced mucosal lesion 3.6-fold
      over the control as well. In contrast, the HCl-induced lesion was inhibited by
      24.4%. These results indicate that not only the acid secretion but also the
      mucosal protection is enhanced after 4-week treatment with omeprazole in rats.

PMID- 9522037
TI  - Electrochemical determination of ibuprofen.
AB  - Two simple and accurate electrochemical methods for the determination of
      ibuprofen (CAS 15687-27-1) as a bulk drug and as an active compound in
      pharmaceutical formulations are presented. For the potentiometric determination
      of ibuprofen sodium hydroxide and triethanolamine were used as titrants. The
      influence of different solvents, such as water, methanol, acetonitrile, dimethyl
      sulfoxide and N,N-dimethylformamide, on the conductometric titrations was
      investigated. The same titrants as in the potentiometric titrations were used.
      The methods are accurate and results are reproducible in quantities ranging from
      1 to 10 mg of ibuprofen in analysed pharmaceutical dosage forms. The relative
      standard deviation (n = 10) varies over the range 0.38-1.63%.

PMID- 9522038
TI  - Investigation on the effect of experimental phospholipase A2 inhibitors on the
      formyl-methionyl-leucyl-phenylalanine-stimulated chemotaxis of human leukocytes
      in vitro.
AB  - We investigated the effects of phospholipase A2 (PLA2) activation and inhibition
      on the chemotaxis of mixed human leukocytes (MHL) in a 48-well microchemotaxis
      chamber and on the production of leukotriene B4 (LTB4) by an enzyme immuno assay.
      LTB4 is the eicosanoid which is most likely responsible for induction of
      chemotaxis and its production can be used as an indicator of PLA2 stimulation.
      Formyl-methionyl-leucyl-phenylalanine (F-met-leu-phe, f-MLP), a well known
      inducer of PLA2 in our experiments stimulated dose-dependently the chemotaxis of
      MHL with a maximum at 10 nmol/l. In accordance with the chemotaxis assay the
      maximum LTB4-production was found at 10 nmol/l f-MLP. The preincubation of MHL
      with the PLA2 inhibitors mepacrine (1-100 mumol/l), manoalide (1-100 mumol/l) and
      BM 16.2115 (1,6-dioxadispiro[4.1.5.1]trideca-8,11-diene-2,10-dione, 0.5-50
      mumol/l) dose-dependently reduced the chemotaxis of MHL induced by 10 nmol/l f
      MLP. The inhibitory effect of the experimental compound BM 16.2115 was about 2
      times stronger than those of the reference compounds mepacrine and manoalide.
      Thus inhibitors of PLA2 reduce chemotaxis of leukocytes probably by reducing
      production of LTB4. This mechanism could be of considerable interest for the
      development of anti-inflammatory drugs.

PMID- 9522039
TI  - Effects of the bisphosphonate zoledronate on bone loss in the ovariectomized and
      in the adjuvant arthritic rat.
AB  - The effect of the bisphosphonate zoledronate (CAS 118072-93-8, CGP 42446) on
      trabecular bone in two rat models of osteopenia, i.e. the ovariectomized rat and
      the adjuvant arthritic rat, was tested and compared to the activity of
      alendronate and pamidronate. All three bisphosphonates prevented bone loss in the
      distal femur and in the lumbar vertebrae in both animal models, as measured by
      chemical analysis and/or bone densitometry. Zoledronate was the most potent
      bisphosphonate, 10-30 times more potent than alendronate and 120 times more
      potent than pamidronate.

PMID- 9522040
TI  - Proteomics--a new way for drug target discovery.
AB  - The results of the genome projects and the obvious problems with handling,
      storing and interpretation of generated data pose a lot of pressure on existing
      strategies in drug target discovery and development of new therapeutic concepts.
      Genomic data, i.e. DNA/RNA sequences identified by subtractive expression pattern
      analysis, are not enough per se for a clear identification of a therapeutic
      target, mainly because proteins and not DNA/RNA are the loci for drug mode-of
      action. The effects seen on the gene expression level are only a response to drug
      effects on the protein level. In addition, there is not always a direct
      correlation between gene expression and protein expression. Therefore, the major
      focus of current efforts in drug discovery is the linkage between the genes and
      the function. One of the most powerful technologies for this purpose is now
      evolving and has been designated as Proteomics.

PMID- 9522041
TI  - Magnesium reduces nickel inhibition of DNA polymerization.
AB  - The activities of DNA polymerization and DNA ligation in extract of Chinese
      hamster ovary cells were both stimulated by MgCl2. DNA polymerization was
      stimulated by MgCl2 above 0.25 mM, whereas, MgCl2 above 2 mM was required to
      stimulate DNA ligation. The activity of DNA polymerization maintained a plateau
      at MgCl2 1-12 mM, whereas DNA ligation reached a maximal activity at MgCl2 6 mM
      and decreased thereafter. NiCl2 0.1-0.2 mM also had a stimulatory effect on DNA
      polymerization, but was much less potent than MgCl2. However, nickel ion (Ni2+)
      had no detectable stimulating effect on the activity of DNA ligation. In the
      presence of MgCl2, the activities of DNA polymerization and DNA ligation
      decreased with increasing concentration of NiCl2. Ni2+ inhibition of DNA
      polymerization was reduced by increasing the concentration of MgCl2, but
      increasing the concentration of MgCl2 did not reduce Ni2+ inhibition of DNA
      ligation. Preincubating cell extract with MgCl2 decreased the Ni2+ inhibition of
      DNA polymerization but not DNA ligation. These results suggest that Ni2+ may
      compete with magnesium ion (Mg2+) to reduce DNA polymerization, but this
      mechanism seems not applicable to Ni2+ inhibition of DNA ligation.

PMID- 9522042
TI  - Effects of acute iron overload on Atlantic salmon (Salmo salar) and rainbow trout
      (Oncorhynchus mykiss).
AB  - Distribution of radioiron to various tissues after intraperitoneal injections was
      examined in Atlantic salmon and rainbow trout. Liver and spleen were found to be
      the major iron storage tissues. Injections of 1 or 5 mg iron as ferric ammonium
      citrate led to a fall in hemoglobin levels in both species after 2 d. Hemoglobin
      levels returned to normal levels in rainbow trout after 8 d, but Atlantic salmon
      had not recovered, and Hb levels fell below 3 g/100 mL. In both species, the fall
      in Hb was associated with a raise in iron levels in spleen and liver, suggesting
      damage to erythrocytes. Atlantic salmon liver ferritin showed a two- to threefold
      increase, while rainbow trout showed a sixfold increase, and a more rapid
      response. The toxic effect of iron in fish appears to be different from the
      effect in other vertebrates.

PMID- 9522043
TI  - Zinc depletion suppresses tumor growth in mice.
AB  - The hypothesis that in tumor-bearing animals an increase of host hepatic zinc
      metallothionein (Zn-MT) causes a restriction of zinc in the tumor tissue was
      studied. Three types of tumors were induced in laboratory mice by cell
      transplant. Tumor growth appears to be inhibited under zinc-deficient conditions,
      even in cases where zinc deficiency was started after tumor cell transplant. The
      survival times of tumor-bearing mice were prolonged by administration of cadmium
      chloride, which induces the synthesis of a combined zinc-cadmium metallothionein
      derivative in the host liver, but not in the tumor tissue, leading to an increase
      of hepatic zinc in the treated animals. The uptake of 65Zn by the liver of Cd
      treated, tumor bearing mice was significantly higher than that of controls
      whereas uptake of 65Zn by tumor cells was significantly higher in controls than
      in the treated animals. These results suggest that restriction of zinc intake
      suppresses tumor growth.

PMID- 9522044
TI  - Increased serum copper and decreased serum zinc levels in children with iron
      deficiency anemia.
AB  - In order to evaluate serum copper and zinc status in children with iron
      deficiency anemia (IDA), 60 children with IDA aged 1-14 yr and 64 healthy
      children as controls aged 1-14 yr were included the study. Serum copper levels
      were higher in children with IDA (189 +/- 49 micrograms/dL) than those of
      controls (163 +/- 37 micrograms/dL) (p = 0.001). Serum zinc levels were lower in
      the patient group (109 +/- 59 micrograms/dL) than those of control subjects (135
      +/- 56 micrograms/dL) (p = 0.017). In addition, there were statistically
      significant negative correlations between hematological parameters and serum
      copper levels in the patient group, but not in controls. No correlation between
      hematological parameters and serum zinc levels were found in both patient and
      control groups, except positive correlation between mean corpuscular volume (MCV)
      and serum zinc level in patients. It was concluded that at the time of managing
      children with IDA, zinc deficiency must be borne in mind and if necessary
      treatment should be initiated with zinc.

PMID- 9522045
TI  - Cerium levels are elevated in the serum of patients with endomyocardial fibrosis
      (EMF).
AB  - The geochemical hypothesis on endomyocardial fibrosis (EMF) links causation of
      the disease to increased levels of cerium in the heart. Since cardiac tissues are
      not easily accessible from patients, we explored whether cerium can be detected
      in the serum using neutron activation analysis (NAA). Cerium levels in serum of
      EMF patients were significantly elevated (p < 0.05) compared to controls.

PMID- 9522046
TI  - Selenium speciation in human milk with special respect to quality control.
AB  - Selenium- (SE) organo compounds of pooled human milk (7th-14th d after delivery)
      were separated by centrifugation and subsequent size-exclusion chromatography
      (SEC) as described in ref. (1). The SEC fractions were used for Se determinations
      by electrothermal vaporization inductively coupled plasma mass spectrometry (ETV
      ICP-MS) in parallel to identification procedures of the organic ligands by two
      different capillary zone electrophoresis (CZE) methods. Further, the combination
      of isotachophoresis- (ITP) CZE with ETV-ICP-MS was used for final
      identifications. Mass balances were carried out at each analytical step for
      quality assurance. Reinjection experiments were performed to check the stability
      of Se-organo compounds during the analytical procedure. These quality-control
      experiments showed that no species transformations took place during the
      analytical procedure, and the Se species were native in human milk. The
      identification and quantification of organic ligands were clear and resulted in
      values of 2 (+/- 0.2) mg/L GSH/GSeH, 2 (+/- 0.22) mg/L cystamine/Se-cystamine, 4
      (+/- 0.4) mg/L cystine/ Se-cystine, and 1 (+/- 0.18) mg/L methionine/Se
      methionine. Unfortunately, a differentiation between sulfur (S) and Se analogs
      was not possible with the applied CE methods. The Se values per organic ligand
      were determined as 2.5 (+/- 0.23) mg/L associated with GSH (as GSeH), 3.1 (+/-
      0.31) mg/L associated with cystamine (as Se-cystamine), 5.2 (+/- 0.4) mg/L
      associated with cystine (as Se-cystine), and 1 (+/- 0.1) mg/L associated with
      methionine (as Se-methionine).

PMID- 9522047
TI  - Multielement determination in small samples of human milk by inductively coupled
      plasma atomic emission spectrometry.
AB  - Inductively coupled plasma atomic emission spectroscopy (ICP-AES) was used for
      routine analysis of small samples of human milk. The concentrations of calcium
      (Ca), copper (Cu), iron (Fe), magnesium (Mg), manganese (Mn), phosphorus (P), and
      zinc (Zn) were determined in 203 milk samples from postpartum women at different
      stages of lactation after stepwise digestion in HNO3, HClO4, and H2O2 under heat.
      Validation of the procedure was achieved using certified reference material of
      bovine liver (NBS 1577) with mean recoveries of 103.5%. The concentrations of the
      above elements in milk matrix were comparable with previously reported values.
      The analytical results from breast milk will provide reference information for
      mineral studies of Brazilian mothers and breast-fed infants.

PMID- 9522048
TI  - Multielemental analysis of human fetal tissues using inductively coupled plasma
      mass spectrometry.
AB  - Inductively coupled plasma-mass spectrometry (ICP-MS) was used to study the
      distribution of 26 major and trace elements in six tissues from 21 human fetuses
      aged 16-22 wk. Brain, lung, spleen, kidney, heart, and liver were analyzed
      following a microwave oven digestion step carried out according to clean
      techniques designed for ultratrace metal analyses. Precision and accuracy
      controls were conducted using standard reference material #1577b Bovine Liver.
      Significant differences among tissues were found for most of the elements.
      Essential trace elements seem to be increasingly retained as fetal tissues mature
      and become physiologically functional. The ranges of concentrations measured in
      fetal tissues at this stage of development are generally lower and much narrower
      than in adult tissues. The age of the fetus, which is not given in most studies,
      as well as the different techniques and levels of quality assurance could be
      responsible for the discrepancies in the trace metal concentrations reported here
      and in the literature. Intratissue homogeneity was also assessed in five human
      fetal brains. Frontal, occipital, parietal and temporal lobes, striatum,
      hippocampus, and thalamus were isolated and analyzed separately. No significant
      differences were found in the distribution of any of the elements at this stage
      of development. Because of the relatively narrow ranges of concentrations found
      for most elements, we believe that the results presented in this study represent
      the inorganic fingerprint of the main tissues of normal fetuses at midpregnancy
      for the Greater Montreal area.

PMID- 9522049
TI  - Trace element contents in hair of residents from Harbin (China), Medan
      (Indonesia), and Tokushima (Japan).
AB  - The concentrations of 19 trace element in hair samples from 1273 residents of
      Harbin (China), Medan (Indonesia), and Tokushima (Japan) were measured by
      inductively coupled plasma emission spectrometry. The mean concentrations of Ba,
      Ca, and Se were significantly higher in the Harbin hair samples when compared to
      those from Medan, but Al, B, Cu, Fe, Mn, Na, Pb, Ti, Zn, and K were significantly
      higher in Medan than in Harbin hair samples. The differences in the mean
      concentrations of As, Cr, Mg, P, Sn, and Sr between the Medan and Harbin lots
      were not significant. In the Tokushima hair samples, Na and K were significantly
      higher, but As, B, Ba, Ca, Cr, Mg, Mn, Pb, Sn, Sr, and Se were significantly
      lower than in the Harbin hair samples. The differences in the mean concentrations
      of Al, Cu, Fe, P, Ti, and Zn between Harbin and Tokushima were not significant.
      In the Medan hair samples, Al, As, B, Ba, Ca, Cr, Cu, Fe, Mg, Mn, Pb, Sn, Sr, Ti,
      and Zn were significantly higher, but P and Se were significantly lower than in
      Tokushima hair samples. Differences in mean concentrations of Na and K between
      Tokushima and Medan were not significant.

PMID- 9522050
TI  - Inhibition of lipid peroxidation.
AB  - Lipid peroxy radicals (ROO.) were detected by electron spin resonance (ESR) at
      low temperature after formation by addition of H2O2 into a suspension of mice
      lymphocytes. If lymphocytes were treated with selenomethionine (Se-Met) prior to
      addition of H2O2, ROO. formation was inhibited in a fashion that was dependent on
      Se-Met concentration. Formation of ROO. in the spleen of mice was induced by 60Co
      irradiation. Animals that were supplemented with Na2SeO3 prior to irradiation
      exhibited a lower ROO. concentration than that of nontreated animals. Based on
      our experiments, we have concluded that Se has an oxygen-free radical scavenging
      effect. This should be a protective effect against lipid peroxy radical cellular
      attack.

PMID- 9522051
TI  - Investigation on arteriosclerosis among population in a rare earth area in south
      China.
AB  - An ophthalmofunduscope was used to investigate arteriosclerosis among villagers
      aged 20-40 yr old in two rare earth areas in Ganzhou, Jiangxi Province. It was
      noted that the occurrence of arteriosclerosis of the fundus aculi was
      significantly high (P < 0.05-0.01), the detection of serum cholesterol (CHO) was
      remarkably increased (P < 0.01), and the level of IgM was also elevated. However,
      high-density lipoprotein (HDL) remained at a low level. The effect of taking rare
      earth elements (REE) could be direct or indirect, thus causing an increase in
      cholesterol and interfering with the synthesis of high-density lipoprotein.
      Furthermore, rare earth could also cause immunogenic damage to the vascular wall.
      All of these could facilitate the formation of arteriosclerosis.

PMID- 9522052
TI  - Zinc deficiency inhibits the direct growth effect of growth hormone on the tibia
      of hypophysectomized rats.
AB  - The effect of zinc deficiency on the direct-growth effect of growth hormone (GH)
      on tibia growth in hypophysectomized rats was studied. There were three dietary
      groups. Zinc deficient (ZD) group (0.9 mg/kg diet), control (C) group (66 mg/kg
      diet) and zinc adequate pair fed (PF) group (66 mg zinc/kg diet). All rats in
      each group received local infusion of recombinant human-growth hormone (hGH) (1
      microgram/d), except for half of the animals in the control group, which were
      sham-treated, receiving vehicle infusion only. The substances were infused
      continuously for 13 d by osmotic minipumps through a catheter implanted into the
      right femoral artery. Food intake was lower and body weight loss was greater in
      ZD, and PF animals compared with C animals (p < 0.001). Tissue-zinc concentration
      and plasma alkaline-phosphatase activity were decreased (p < 0.05) by dietary
      zinc deficiency. GH infusion increased the tibial-epiphyseal width of the treated
      right limb, but not of the noninfused left limb in C and PF animals. However, in
      ZD rats, no difference was found between the infused and the noninfused limbs.
      These results demonstrate that zinc deficiency inhibits the direct-growth effect
      of GH on long-bone growth.

PMID- 9522053
TI  - The pH dependence of silicon-iron interaction in rats.
AB  - A 2 x 2 x 3 factorial experiment was conducted to study the pH dependence of a
      silicon-iron interaction in vivo. The dietary treatments used in the factorial
      design were the following (mg/kg of diet): silicon, 0 and 500; iron, 35 and 187;
      acid-base, ammonium chloride as 0.5% of total diet (acidic), sodium bicarbonate
      as 1.0% of total diet (basic), or no supplementation of acid or base (control).
      The supplementation of 500 mg silicon/kg of diet increased plasma-iron
      concentration in rats fed the acidic or control diets, but not in rats fed the
      basic diet. A high dietary-iron level suppressed copper absorption and
      utilization and subsequently imposed a negative effect on its own utilization. An
      increase in the plasma total-cholesterol concentration caused by high dietary
      iron level was likely a consequence of the antagonistic effect of iron on copper
      absorption and utilization. The use of cupric sulfate pentahydrate as the dietary
      copper source in this study resulted in plasma copper concentrations that were
      approximately twice those obtained in a related study using cupric carbonate.
      Also, a 42% coefficient of variation (C.V.) for plasma-copper concentrations of
      rats fed cupric sulfate in this study was greatly reduced from the C.V. = 108%
      previously associated with the dietary cupric carbonate.

PMID- 9522054
TI  - Biochemical interactions among silicon, iron and ascorbic acid in the rat.
AB  - A 2 x 2 x 2 factorial experiment was conducted using two dietary levels each
      (mg/kg of diet) of silicon, 0 and 500; iron, 35 and 187; and ascorbic acid, 0 and
      900, to identify biochemical interactions occurring among these nutrients.
      Supplemental silicon, in conjunction with the higher dietary-iron level,
      prevented the plasma-iron decreasing effect observed for the higher level of iron
      in the absence of silicon. In the absence of ascorbic acid, silicon also
      increased iron concentration in the liver. Lower growth of the silicon and iron
      supplemented rats is believed to be a response to a subsequent iron-imposed
      aberration of copper or zinc metabolism. This is supported by decreased
      intestinal metallothionein, increased weights (g/100 g body weight) of liver,
      heart, and testes, and decreased packed-cell volume and hemoglobin concentration.
      The lower plasma-iron level associated with the higher level of dietary iron
      appeared to be an expression of the iron-imposed reduction of liver copper
      stores. Ascorbic acid decreased plasma-iron concentration and prevented the
      silicon-related increase in liver iron.

PMID- 9522055
TI  - Alterations in lipid composition and neuronal injury in primates following
      chronic aluminium exposure.
AB  - The effect of chronic aluminium exposure (25 mg/kg b.wt.) was studied on the
      lipid composition and various membrane-bound enzymes in different regions of
      monkey brain. Aluminium (Al) administration caused a significant decrease in the
      total lipid, glycolipid, and phospholipid content of primate brain. Cholesterol
      levels and the phospholipid to cholesterol ratio were, however, markedly
      increased as a consequence of Al administration, thereby indicating a loss of
      membrane integrity. This was further confirmed when Al treatment was found to
      have a significant effect on the various membrane-bound enzymes in terms of
      decreased activities of Na+ K+ ATPase and acetylcholinesterase, along with a
      decrease in the activity of the myelin-specific enzyme, 2' 3'-cyclic nucleotide
      phosphohydrolase.

PMID- 9522056
TI  - Zinc and cadmium analysis in human prostate neoplasms.
AB  - The objective of this study was to test the hypothesis that prostatic cancer is
      associated with the changes of zinc (Zn) and cadmium (Cd) concentration. Normal
      prostate, benign prostatic hyperplasia (BPH), and prostatic carcinoma (PCA) were
      analyzed for Zn and Cd by atomic absorption spectrometry. Cd level was measured
      using a graphite furnace and Zn level was measured by flame mode. Metal content
      was assessed in whole tissues and in nuclear, plasma membrane, and cytosolic
      fractions. An increase of Zn content in BPH, but a decrease in PCA as compared to
      normal tissue, was observed. Cd concentration appeared to be higher in BPH and
      PCA than in normal tissue. No correlation between Zn and Cd level was found in
      BPH specimens obtained from the same patients. Probability values of p < or =
      0.05 were considered to indicate significant differences. Obtained results seem
      to support the hypothesis of Cd carcinogenicity and preventing function of Zn in
      prostatic cancer. Plasma membrane fraction corresponding to lysosomal,
      mitochondrial, and microsomal subcellular compartments are probably critical in
      Zn and Cd participation in human prostate neoplasms.

PMID- 9522057
TI  - Serum and milk iron levels during sheep intramammary infection caused by
      coagulase-negative staphylococci.
AB  - The concentration of iron (Fe) in the milk and serum of sheep was determined
      before and during experimental intramammary infection (IMI) by coagulase-negative
      staphylococci (C-NS). Fe concentration of normal milk and serum samples was 0.24
      microgram/mL and 1.56 micrograms/mL respectively. Presence of C-NS in the mammary
      gland resulted in a significant increase in milk-iron concentration (p < 0.001)
      and a decrease in the serum-iron concentration. Serum-iron concentration was
      significantly decreased (p = 0.04) one d after the intramammary introduction of C
      NS and 29 d later (p = 0.03).

PMID- 9522060
TI  - High accumulations of calcium and phosphorus in women's pubic symphysis.
AB  - To elucidate compositional changes of the pubic symphysis (PS) by aging, elements
      of pubic symphysis (PSs) removed from 26 cadavers were determined by inductively
      coupled plasma atomic-emission spectrometry. It was found that the relative
      contents (RCs) of calcium and phosphorus in women's PSs were about three- and
      five-fold amounts as compared with those in men's PSs, respectively. In contrast,
      the RCs of sulfur, magnesium, sodium, and iron in women's PSs were somewhat lower
      than those in men's PSs. The accumulations of calcium (Ca) and phosphorus (P) in
      women's PSs occurred mainly beyond the age of 70-yr-old, but did not occur in
      men's PSs.

PMID- 9522059
TI  - Age-independent constancy of mineral contents in human vertebra and auditory
      ossicle.
AB  - To elucidate age-related changes of mineral contents in human bones, element
      contents of human vertebrae and auditory ossicles were determined by inductively
      coupled plasma atomic-emission spectrometry. The cervical, thoracic, and lumbar
      vertebrae were removed from 12 vertebral columns. The mallei of auditory ossicle
      were removed from 27 cadavers. It was found that average relative contents (RCs)
      of calcium and phosphorus in cervical, thoracic, and lumbar vertebrae remained
      almost constant within ages ranging from 46 to 99 y. In addition, it was found
      that the RCs of calcium and phosphorus in men's and women's mallei remained
      constant within ages ranging from 40 to 98 yr. These results support the view
      that there is no significant age-dependent change of mineral contents in human
      bones.

PMID- 9522058
TI  - Effect of lithium on hepatic drug-metabolizing enzymes of protein-deficient rats.
AB  - Protein deficiency was produced by feeding synthetic 8%-protein diet. Lithium
      carbonate at the dose level of 1.1g/kg diet was administered to normal and
      protein-deficient rats for a period of one mo. A significant inhibition in the
      levels of cytochrome (cyt) P450, cyt b5, glutathione (GSH), glutathione S
      transferase (GST) and glutathione peroxidase (GPx), but an increase in gamma
      glutamyl transpeptidase (gamma-GT), was observed in low-protein LP-fed rats.
      Lithium treatment to normal rats caused no significant change in the activities
      of cyt P450, cyt b5, GST, and GSH levels, whereas there was elevation in the
      activities of gamma-GT and GPx and suppression in glutathione reductase (GRd)
      activity. Lithium administration to LP-fed rats resulted in significant increases
      in the hepatic gamma-GT and GPx activities.

PMID- 9522061
TI  - Effect of selenium supplementation on mice infected with LP-BM5 MuLV, a murine
      AIDS model.
AB  - LP-BM5 Murine leukemia virus (MuLV) infection of C57BL/6 mice develop a disease
      that has many features in common with human acquired immunodeficiency syndrome
      (AIDS), in particular abnormal lymphoproliferation and severe immunodeficiency.
      Thus, this MAIDS model may be useful for evaluation of potent antirival agents in
      vivo. Deficiency in antioxidant micronutrients such as selenium, zinc, and
      glutathione have been observed in AIDs and AIDS-related complex (ARC) patients.
      In the present study, the MAIDS model was used to evaluate immunological and
      oxidative effect of Se as sodium selenite. Results indicated that Se treatment
      0.1 mg/kg/d (p.o.) inhibited splenomegaly and sera IgG elevation effectively. In
      addition to abnormal immunity, oxidative imbalance possibly existed in MAIDS
      model, as lipid peroxide increased significantly in spleen and whole blood
      glutathione peroxidase (GSH-Px) activity decreased markedly. Se supplementation
      had good protective effect.

PMID- 9522062
TI  - Effects of dietary selenium and vitamin E concentrations on phospholipid
      hydroperoxide glutathione peroxidase expression in reproductive tissues of
      pubertal maturing male rats.
AB  - Phospholipid hydroperoxide glutathione peroxidase (PHGPX) is the second
      intracellular selenium (Se)-dependent glutathione peroxidase (GSH-Px) identified
      in mammals. Our objectives were to determine the effect of dietary vitamin E and
      Se levels on PHGPX activity expression in testis, epididymis, and seminal
      vesicles of pubertal maturing rats, and the relationship of PHGPX expression with
      testicular development and sperm quality. Forty Sprague-Dawley male weanling rats
      (21-d old), were initially fed for 3 wk a torula yeast basal diet (containing
      0.05 mg Se/kg) supplemented with marginal levels of Se (0.1 mg/kg as Na2SeO3) and
      vitamin E (25 IU/kg as all-rac-alpha-tocopheryl acetate). Then, rats were fed the
      basal diets supplemented with 0 or 0.2 mg Se/kg and 0 or 100 IU vitamin E/kg diet
      during the 3-wk period of pubertal maturing. Compared with the Se-supplemented
      rats, those fed the Se-deficient diets retained 31, 88, 67, and 50% of Se
      dependent GSH-Px activities in liver, testis, epididymis, and seminal vesicles,
      respectively. Testes and seminal vesicles had substantially higher (5- to 20
      fold) PHGPX activity than liver. Dietary Se deficiency did not affect PHGPX
      activities in the reproductive tissues, but reduced PHGPX activity in liver by
      28% (P < 0.0001). Dietary vitamin E supplementation did not affect PHGPX activity
      in liver, whereas it raised PHGPX activity in seminal vesicles by 43% (P <
      0.005). Neither dietary vitamin E nor Se levels affected body weight gains,
      reproductive organ weights, or sperm counts and morphology. In conclusion,
      expression of PHGPX activity in testis and seminal vesicles was high and
      regulated by dietary Se and vitamin E differently from that in liver.

PMID- 9522063
TI  - Paleodietary analysis on the prehistoric population of El Hierro (Canary
      Islands).
AB  - In order to deepen our knowledge of the dietary habits of the prehispanic
      inhabitants of El Hierro, we have determined bone strontium (Sr), manganese (Mn),
      magnesium (Mg), copper (Cu), zinc (Zn), and calcium (Ca) in 52 human tibiae (23
      belonging to male and 20 to female individuals) buried in a single burial cave;
      in 21 modern individuals who served as controls; and in 11 bones of herbivores
      found at archeological sites of the Canary Islands. Results suggest that females
      consumed a more vegetarian diet, although site-corrected Sr/Ca ratio of both
      males and females speaks for a mixed-diet consumption.

PMID- 9522064
TI  - [Surgical technical guidelines in intestinal ischemia].
AB  - Acute occlusive mesenteric ischemia is caused by a local impairment of splanchnic
      blood flow and poses a particular surgical challenge. Acute superior mesenteric
      occlusion is a medical/surgical emergency mandating prompt diagnosis (clinical
      awareness, angiography) and therapy (exploratory laparotomy with possible
      arterial reconstruction; embolectomy, thrombectomy; and/or bowel resection). The
      difficulty of early diagnosis is probably the most important cause of the high
      mortality which varies from 70% to 90% in arterial and functional mesenteric
      ischemia and from 20% to 70% in an acute thrombosis of the mesenteric veins.
      Improved survival from nonocclusive mesenteric ischemia is dependent upon the
      identification of high-risk groups and on aggressive diagnostic and therapeutic
      measures (intra-arterial infusion of papaverine through the angiographic catheter
      with or without bowel resection). For assessment of bowel viability, the clinical
      judgement during first- or second-look exploration is still the most reliable
      parameter. The surgical management of chronic mesenteric ischemia includes
      aortomesenteric grafting and transaortic endarterectomy in the majority of
      patients with comorbidity of cardiovascular arteriosclerotic diseases and results
      in a high rate of symptom-free patients. Prophylactic reconstruction of visceral
      arteries is indicated only in certain limited circumstances.

PMID- 9522065
TI  - [Vascular surgery within the scope of visceral surgery-oncologic interventions].
AB  - The surgeon dealing with oncological operations within the abdominal cavity will
      be frequently confronted with vascular problems. These include surgically
      relevant vascular anomalies, arteriosclerotic changes, tumor infiltration of
      vessels and iatrogenic vascular lesions. The diagnosis, indications and, above
      all, the vascular surgical techniques applied during oncological procedures on
      the pancreas and liver are described in this review.

PMID- 9522066
TI  - [Surgical technique and surgical-oncologic tactics in tumors of soft tissues and
      extremities with vascular involvements].
AB  - Patients suffering from soft tissue sarcoma of the extremities may sometimes
      require vascular reconstruction to remove the tumor with adequate margins of
      clearance. Besides this, recurrent lymph node metastases are often affixed to
      neighboring vessels. MRI and angiography represent the adequate diagnostic
      procedures. Vessel-invasive sarcoma can hardly be treated by surgical resection
      with curative intent alone. If there is doubt about invasion of arteries and
      veins, the vessels should be resected and replaced by autologous vein graft. Soft
      tissue coverage is of major importance, particularly if prosthetic grafts are
      used or the resection is within an area of irradiated tissue. After radical
      resection and combined modality therapy, one can expect local recurrence rates
      similar to those without vessel invasion. To achieve this goal, surgical
      oncologists, vascular surgeons and plastic surgeons must work together. Today,
      amputation can hardly be justified even in vessel-invasive soft tissue tumors.

PMID- 9522067
TI  - [Ruptured aortic aneurysm as an unexpected finding in laparotomy for acute
      abdomen].
AB  - The ruptured abdominal aortic aneurysm as an incidental finding in emergency
      laparotomy for acute abdominal symptoms is a rare event. For this reason it is
      more important to know the necessary diagnostic and therapeutic strategies.
      Nowadays sonography facilitates the preoperative diagnosis. The performance of an
      additional computed tomography or angiography depends on the clinical appearance
      of the patient. In hemodynamically instable patients with a ruptured aneurysm, an
      immediate laparotomy is mandatory. If intraoperatively the aortic aneurysm has a
      diameter of more than 5 cm and shows no signs of rupture, implantation of an
      aortic prosthesis is indicated. This procedure has also priority when patients
      with a ruptured aneurysm are suffering from an additional abdominal disease. If
      additional septic reasons are diagnosed intraoperatively, the abdominal operation
      has to be performed synchronously with the aortic prosthesis. Alternatively, the
      use of an antimicrobial vascular prosthesis or resection of the aortic aneurysm
      with extra-anatomic bypass has to be considered. The technical difficulty of the
      operation is in the control of the proximal aorta. The lethality of operations
      for ruptured aneurysm has been consisted high (between 21 and 70%) in the past.
      In an elective operation, mortality has how improved up to 5%. This indicates
      that the essential prognostic factors, degree of retroperitoneal hematoma and
      hemorrhagic shock, and the condition of the patient, are not influenced by modern
      patient management. However, a further dominant prognostic parameter for
      lethality, how qualified the surgeon is in vascular surgery, can be influential.

PMID- 9522068
TI  - [Vascular surgery techniques in peripheral vascular embolism].
AB  - Acute limb ischemia is an emergency which regularly requires operative treatment
      in departments of general surgery. In about 70% of cases there is an embolic
      reason for acute ischemia. In the majority of cases urgent operative
      desobliteration is required to guarantee limb salvage. The introduction of
      balloon catheters reduced the surgical trauma significantly in cases of long
      secondary thromboses. More complex procedures are required in patients with
      preexisting chronic arterial occlusive disease. The mortality of these emergency
      operations is still 10-20% with a limb salvage rate of 80-90%.

PMID- 9522069
TI  - [Hemorrhagic pseudocysts and pseudoaneurysms in pancreatitis. Diagnosis and
      therapy].
AB  - Acute hemorrhage from pseudocysts and pseudoaneurysms is a threatening
      complication of chronic pancreatitis. Whilst surgical intervention still has high
      perioperative mortality (16.8%), transcatheter arterial embolization is becoming
      more frequently used for suitable cases and appears to have lower mortality
      (6.1%). We report on six patients treated in our unit. Four of them underwent
      primary surgical treatment, the other two were treated by embolisation. One of
      the latter patients subsequently required laparotomy for further treatment. All
      six patients survived. Comparing the literature covering the periods between 1951
      and 1981 and between 1982 and 1996, transcatheter embolisation seems to be
      valuable in controlling this type of bleeding, thereby reducing mortality.

PMID- 9522070
TI  - [Postcholecystectomy complaints one year after laparoscopic cholecystectomy.
      Results of a prospective study of 253 patients].
AB  - AIMS: We studied the nature and frequency of symptoms 1 year after laparoscopic
      cholecystectomy in order to define pre- and perioperative factors that influence
      the long-term outcome. METHOD: Between September 1994 and August 1995 we
      prospectively evaluated 268 patients undergoing laparoscopic cholecystectomy
      using a standard questionnaire. After an average of 16 months (12-25 months) the
      patients were asked about their symptoms using a similar questionnaire by
      telephone or were followed up clinically if necessary. RESULTS: In the long-term
      follow-up the severity of the symptoms according to the Visick score were: Visick
      I (no symptoms): 164 patients (65%); Visick II: 72 (28%); Visick III: 12 (5%);
      Visick IV: 5 (2%). The aetiologies of the postcholecystectomy syndrome were:
      residual stones 1%, subhepatic liquid formation 0.8%, incisional hernia 0.4%,
      peptic diseases 4%, wound pain 2.4%, functional disorders 26%. Patients with
      typical or atypical symptoms preoperatively showed no difference in the outcome 1
      year after laparoscopic cholecystectomy. Neither did the number and location of
      laparotomies prior to cholecystectomy or the gallbladder perforation or loss of
      stones intraoperatively influence the severity of the postcholecystectomy
      symptoms. CONCLUSIONS: One year after laparoscopic cholecystectomy 93% of the
      patients have no or only minor abdominal symptoms. Neither the number and
      location of the laparotomies prior to cholecystectomy nor the loss of gallstones
      intraoperatively have an impact on the long-term result.

PMID- 9522071
TI  - [Cholecystectomy in high risk patients. A comparison between conventional and
      laparoscopic procedures].
AB  - Laparoscopic cholecystectomy offers many advantages, but cardiopulmonary impaired
      patients may be endangered by the haemodynamic and respiratory effects of the
      pneumoperitoneum. Between June 1990 and December 1995, laparoscopic
      cholecystectomies were performed on 19 high-risk patients (ASA IV) and
      conventional cholecystectomies on 26 patients with the same operative risk (ASA
      IV). Out of 45 patients, 5 (11.1%) suffered intraoperative cardiopulmonal
      complications. Three belonged to the group with laparoscopic cholecystectomy
      (15.8%) and two to the group with open laparotomy (7.7%). General postoperative
      complications occurred in 15 cases (33.3%), whereby patients of the conventional
      cholecystectomy group were concerned more often [46.2% (n = 12) versus 15.8% (n =
      3), P = 0.03]. The number of days spent in hospital after open cholecystectomy
      was higher (P = 0.01) (11.6 +/- 5.6 days in the laparotomy group versus 7.6 +/-
      5.0 days in the laparoscopy group). The classification as a high-risk patient
      indicates an elevation of the perioperative rate of complications in laparoscopic
      and open cholecystectomy, whereby the rate of postoperative complications is
      lower in the laparoscopic group.

PMID- 9522072
TI  - [Simplified appendectomy without stump embedding. Experiences of 20 years
      conventional and 5 years laparoscopic application].
AB  - Since 1975, the Department of Surgery in the Grevenbroich Community Hospital
      (Germany) has applied a simplified technique of open appendectomy. The inhouse
      modified procedure without stump embedding has been performed in 3,448 cases to
      date. The same approach has been used in 1,463 laparoscopic appendectomies since
      1991. In the laparoscopic procedure the stump is ligated solely with Roeder's
      loop. None of the 4,911 patients who have undergone either open or laparoscopic
      appendectomy have developed stump inadequacy or stercoral fistulae. According to
      the special literature, the complication rate after appendectomies without stump
      embedding is lower than that after standard procedures. In retrospect,
      laparoscopic appendectomy with simple ligation has confirmed the results achieved
      with simple ligation in open appendectomies. The technique should therefore
      become more common practice in open appendectomies, as well.

PMID- 9522074
TI  - [Except from the speech "Small Trilogy" on the occasion of the emeritus forum of
      Professor Dr. med. Dr. med. h. c. Michael Trede September 20, 1997, Mannheim].

PMID- 9522073
TI  - [Carbohydrate-deficient transferrin (CDT) as preoperative alcohol marker in
      surgical risk patients].
AB  - In a prospective study the preoperative risk of alcohol addiction was evaluated
      in 46 patients with squamous cell carcinoma of the esophagus. In all patients the
      alcohol marker carbohydrate-deficient transferrin (CDT) was measured prior to
      esophagectomy and correlated with the incidence of postoperative withdrawal
      symptoms (yes/no) and the postoperative course (good/moderate/poor/fatal).
      Withdrawal symptoms were more frequently observed in cases of elevated CDT values
      (median of CDT with withdrawal 17.0 U/l vs without withdrawal 10.7 U/l; P =
      0.0006). CDT values were significantly increased in case of a complicated
      postoperative course (median of CDT for moderate/poor/fatal postoperative course
      14.0 U/l vs good course 10.8 U/l; P = 0.02). The CDT value correlated (P = 0.04)
      with the patient's history of preoperative alcohol consumption
      (normal/increased/high). In a multivariate logistic regression analysis CDT and
      preoperative alcohol consumption were independent parameters to predict
      significantly the postoperative course and withdrawal. The sensitivity was 71.4%
      and the specificity 84.4% selecting the parameter "postoperative withdrawal" and
      a CDT cut-off point of < 15.3 U/l. CDT can effectively identify patients with
      high alcohol consumption prior to esophagectomy.

PMID- 9522075
TI  - [Surgeons in humanitarian medical emergency aid exemplified by the mission
      Physicians without Boundaries in Kismayo/Somalia in January 1997].

PMID- 9522076
TI  - [Definitions for perioperative performance analysis].

PMID- 9522077
TI  - [Restructuring due to the development clause. Decision of the Federal Employment
      Court 28 May 1997--5 AZR 125/96].

PMID- 9522078
TI  - [Physicians in France].

PMID- 9522079
TI  - [Graduate curriculum "ambulatory surgery" for physician assistants].

PMID- 9522080
TI  - [Individual prognosis of critically ill patients with septic shock by neural
      network?].
AB  - From 1. 11. 93 to 30. 3. 97, 1149 patients were prospectively studied during
      their ICU stay. Of them, 114 met the criteria of septic shock, with lethality of
      47.3%. A neural network was trained with datasets from 91 of these 114 patients.
      Testing the trained neural network with the remaining 23 patients, the following
      result was obtained: all 10 patients dying from septic shock were correctly
      predicted; of 13 surviving patients, 12 were correctly identified (sensitivity
      100%; specificity 92.3%).

PMID- 9522081
TI  - [Glycosaminoglycans as markers of post-traumatic gonarthrosis?].
AB  - Osteoarthritis (OA) influences the levels of free intraarticular
      glucosaminoglycans (GAG). Little is known about the direction--decrease/increase-
      of these changes, and information on the correlation between GAG levels and the
      degree of OA is sparse. Objectives of this study were to investigate the
      correlation between intraarticular levels of sulphated and unsulphated GAG and
      the degree of experimental OA, the time course of these changes and whether GAG
      might be useful as a marker for OA. Twenty-one sheep were randomly assigned to
      three groups: (1) transsection of the posterolateral bundle of the anterior
      cruciate ligament, ACL (TD), (2) medial meniscectomy (ME), and (3) meniscectomy
      and resection of the ACL (MV). During follow-up clinical and radiological
      examinations were done. After screening for intraarticular effusions, a joint tab
      was performed and the levels of hyaluronic acid and chondroitin sulphate were
      measured. The radiological scores differ significantly between group TD and
      groups ME and MV (P < 0.01). Hyaluronic acid levels in ME and MV are
      significantly higher than in the controls. Significantly increased levels (P <
      0.01) of chondroitin sulphate are found 6 months after ME and 1 year following
      TD. Clinical consequences: Hyaluronic acid levels--at least in the experimental
      setting--correspond to a certain degree with osteoarthrotic changes: increasing
      levels were found along with increasing postoperative interval and increasing
      grade of OA. Chondroitin sulphate, on the other hand seems, to lend itself as a
      marker for chondromalacia, in other words for prearthrotic deformities and early
      stages of OA.

PMID- 9522082
TI  - [Post-traumatic arteriovenous fistula between splenic artery and vein as a rare
      cause of acute myocardial ischemia].
AB  - Arteriovenous fistulas of the portal system are rare. Congenital fistulas have to
      be differentiated from acquired fistulas; the latter are of posttraumatic or
      iatrogenic origin. The case presented demonstrates a history of diffuse abdominal
      pain and the first description of myocardial ischemia caused by a posttraumatic
      splenic arterioportal fistula. After diagnostic and therapeutic difficulties, the
      definitive treatment consisted in resection of the fistula system including the
      pancreatic tail.

PMID- 9522083
TI  - [Iatrogenic arteriovenous fistulas of the vertebral artery after venipuncture of
      the neck. Vascular surgery treatment and long-term outcome].
AB  - Direct puncture of the vertebral artery for angiography has been abandoned since
      the introduction of angiography catheters. Nowadays puncture of jugular veins for
      intravenous nutrition or monitoring is the predominant cause of accidental
      arteriovenous vertebral artery fistulas. We describe the history of four patients
      with such fistulas and the long-term results after surgical repair.

PMID- 9522084
TI  - [Renal angiomyolipoma as a rare cause of retroperitoneal hemorrhage].
AB  - Angiomyolipomas are hamartomas that may be found sporadically or associated with
      tuberous sclerosis (M. Bourneville-Pringle). Clinically, this long-term
      asymptomatic tumor becomes evident as an acute retroperitoneal hemorrhage or by
      symptoms of a flank mass. Due to the high percentage of fat components in this
      tumor type, computed tomography is far superior to other radiological procedures.
      In view of two of our own case reports, the therapeutic strategies are discussed,
      paying regard to the actual literature in this field.

PMID- 9522085
TI  - [Diagnosis and therapy of hypothenar hammer syndrome].
AB  - Traumatic injuries of arteries lead to acute bleeding or ischemia. In the hand,
      which is perfused by two arteries, this symptom could be missed. The hypothenar
      hammer syndrome is a traumatic occlusion of the distal arteria ulnaris. Dependent
      on the mechanism of the trauma the clinical symptoms may appear late. A specific
      angiographic or duplex sonographic diagnostic investigation is necessary to show
      the arterial occlusion. There is no proven therapeutic procedure. Exact diagnosis
      of the occlusion as an effect of the trauma is important for the patient and is
      the basis of any therapeutic intervention.

PMID- 9522086
TI  - [Zwickau surgery from Karl Hermann Karg to Frank Otto Mayer].
AB  - Zwickau Hospital in Saxony has been a famous center of surgery since the very
      beginning. It was built by Heinrich Braun, the founder of modern local
      anesthesia. His successors, Kulenkampff and Mayer, preserved, continued and
      completed his life's work. The surgery center in Zwickau provided very important
      ideas for general and local anesthesia, for building and managing hospital and
      for the science of surgery in words and illustrations.

PMID- 9522087
TI  - [Fascia transversalis in inguinal hernia repair with total extraperitoneal
      plasty. Comment on the contribution by H. Witte et al].

PMID- 9522088
TI  - [Infiltrating intramuscular lipoma. Comment on the contribution by H. Schellong
      et al].

PMID- 9522089
TI  - [Deep rectum resection and inter-sphincter rectum excision. Comment on the
      contribution by H.-P. Bruch and G. Kolbert].

PMID- 9522090
TI  - [Treatment of rupture of the Achilles tendon].

PMID- 9522092
TI  - [Gastric neurinoma].

PMID- 9522091
TI  - [Primary adenocarcinoma of the duodenum].
AB  - Adenocarcinoma of the duodenum represents a rare neoplasia characterized by an
      indefinite symptomatology, at least early, and deceitful, that, therefore,
      arrives at surgeon, almost always, in advanced stage. The Authors, taking from a
      clinical case, recently observed, as a starting point, review the literature,
      referring the etiopathogenetic hypothesis that explain the relative rarity of
      this neoplasia. They therefore report the diagnostic and therapeutic procedure to
      carry out in these patients.

PMID- 9522093
TI  - Gastric stump cancer after stomach resection due to peptic disease.
AB  - Stump cancer is the most severe late complication of stomach resection due to
      peptic disease. Recent clinical studies show an increase in the incidence of
      gastric carcinoma in patients who underwent stomach resection, in comparison to
      the general population. Cancers detected within the first four years following
      resection are considered a consequence of false pathological diagnosis. The
      etiologic factors which contribute to the development of "late" gastric
      carcinomas (20-40 years after initial operation) remain unknown. In this
      retrospective study, we have analysed the incidence of stomach cancer in the
      whole population of patients operated for peptic disease (stomach resection
      methods and vagotomy) in our Department over the "1973 to 1993" period. A total
      of 1343 patients were operated on for malignant diseases of the stomach, and 4531
      patients underwent surgery for peptic disease. Gastric stump cancer surgery was
      performed in 35 (0.8%) patients following resection of the stomach for peptic
      disease. Their mean age was 63.5 years. An average of 21.4 years elapsed from the
      initial surgery to the diagnosis and reoperation of the stump cancer. Results of
      the study point to the importance of a systematic follow-up of patients who
      underwent stomach surgery due to peptic disease regardless of the surgery
      applied. Early detection of stomach cancer in previously operated patients is the
      most important factor contributing to their successful treatment.

PMID- 9522094
TI  - [Our experience in the treatment of intrathoracic and intraspinal hourglass
      neurogenic neoplasms].
AB  - The authors describe their experience in the treatment of dumbbell neurogenic
      tumours, intrathoracic and intraspinal, with particular reference to clinical
      presentation, diagnostic for imaging, anatomo-pathological classification and
      surgical treatment, comparing their clinical cases (9) with the international
      literature, accurately reviewed. The authors think that the best surgical
      treatment is the combined approach, in only one stage, of thoracic surgeon and
      neurosurgeon by hemilaminectomy and extended costotrasversectomy, reserving
      hemilaminectomy and thoracotomy only for the tumours with big dimension of
      intrathoracic portion.

PMID- 9522095
TI  - [Acute biliary pancreatitis: mini-invasive treatment].
AB  - Acute biliary pancreatitis (ABP) still retains high morbidity (15-50%) and
      mortality (20-35%). Therefore it appears to be crucial clearly assessing the
      aetiological factors (50% of idiopathic are in fact biliary pancreatitis) and
      establishing the severity in order to plan the appropriate treatment. Forty-nine
      ABP patients were diagnosed by ultrasound (75.5%) or by laboratory findings
      (22.5%). Following Ranson and APACHE II scoring, 15 cases (30.6%) were classified
      as severe, 34 (69.3%) as mild. All patients with severe ABP had emergency ERCP +
      ES (within 24-48 hours) followed by LC (< or = 10 days). Patients with mild ABP
      had LC within 10 days; in these cases IOC was always done. In severe cases
      operative endoscopy cured pancreatic inflammation in 11 cases. Subsequent LC
      never showed serious morbidity, but subcutaneous emphysema in one case. In 4
      cases laparotomy was required since pancreatic necrosis was present, with 75%
      mortality. In patients with mild pancreatitis LC was successfully performed in
      all cases, with 8.8% morbidity. IOC showed choledochal stones in 32.5% of cases,
      while in severe cases stones in the biliary tree were showed in 80% of cases. In
      conclusion ABP treatment is always surgical, and almost always with minimally
      invasive procedures in severe cases (ERCP + ES with LC < or = 10 days) if surgery
      is performed within 24-48 hours as well as in mild cases (LC + IOC) when surgery
      is done within 10 days.

PMID- 9522096
TI  - [Acute cholecystitis: video-laparoscopic or laparotomic treatment? Role of the
      immune system].
AB  - Recent clinical studies suggest that laparoscopic cholecystectomy (LC) causes
      less depression of cell-mediated immunity than open cholecystectomy. LC is a so
      called "mini invasive" surgical presidia, and on the basis of this consideration
      we have investigated if and how the immune response is modified in patients with
      acute cholecystitis after laparoscopic cholecystectomy compare to patients
      undergone open cholecystectomy. Immune-activity (neutrophils, total lymphocytes
      count, lymphocytes subpopulations, HLA-DR, 6-Interleukin, skin multitests) was
      evaluated in 28 patients 24-36 hours before surgery and p.o. after 1, 3 and 6
      days: 16 patients underwent "open" cholecystectomy and 12 LC. One day after
      surgery patients with open cholecystectomy showed significant increase (p < or =
      0.05) of plasma neutrophils and 6-Interleukin, while these parameters were almost
      unchanged in patients with LC. Moreover, skin tests showed ipo or anergic
      response in the majority (81.8%) of patients with "open" surgery compare to
      patients with LC (10.5%): (p < or = 0.05). Finally monocyte antigen HLA-DR was
      also reduced in patients with "open" cholecystectomy: in this group we also
      recorded 2 cases (12.5%) of respiratory tract infection. In conclusion, LC for
      acute cholecystitis, avoids p.o. immunosuppression with better p.o. morbidity
      compare to open surgery.

PMID- 9522097
TI  - [Cholangiojejunostomy of the duct of the 3d segment. Palliative treatment of
      cholestatic jaundice caused by neoplastic obstruction of the hepatic hilus].
AB  - Cholangiojejunostomy of the duct of the III segment in the palliative treatment
      of mechanical jaundice from neoplastic obstruction of the hepatic hilus. The
      neoplastic obstruction of the liver hilus has an almost total absence of
      forewarning clinical signs and therefore results in surgery at a late stage when
      the patient is not susceptible to radical treatment. It is therefore necessary to
      use palliative treatment in order to resolve the serious jaundice, the main cause
      of a quick death. Among the palliative treatment the Authors report their
      experience of intrahepatic cholangiojejunostomy of the duct of the III segment
      that they consider the most suitable technique for its ease of execution, its
      constant anatomical situation and the peripheral position of the anastomoses in
      relation to the neoplastic lesion. This allows a lasting biliary decompression
      with a good residual life.

PMID- 9522098
TI  - [Ambulatory treatment of inguinal hernia].
AB  - The Authors report their experience about the inguinal hernioplasty operation by
      implantation of prostheses in prolene following the Licthenstein technique.
      Prolene mesh strengthens the inguinal canal wall, with no suture tension point.
      The technique is performed under local anesthesia, in day-hospital system,
      consenting the patient a rapid reinstatement in the social-working ambit.

PMID- 9522099
TI  - [Chronic abdominal pain: role of video-laparoscopic adhesiolysis].
AB  - Adhesions have been suggested as a possible cause of chronic abdominal pain, but
      the reports of their etiological role conflict. Lysis of adhesions has been
      proposed as the therapeutic modality of choice, although the reports of success
      are controversial. The aim our prospective study was to determine whether
      laparoscopic adhesiolysis ameliorates chronic abdominal pain in patients with
      abdominal adhesions. Forty-one patients with chronic abdominal pain lasting for
      more than 6 months, but with no abnormal findings other than adhesions found at
      laparoscopy, underwent laparoscopic adhesiolysis. 37 patients (90.2%) were
      available for follow-up after a median time interval of 18 months (range: 12-41
      months). Twenty-two patients (59.4%) were free from abdominal pain and 9 (24.3%)
      patients reported significant amelioration of their pain. Six (16.2%) patients
      had no amelioration. In conclusion the laparoscopy is an effective tool for the
      evaluation of patients with chronic abdominal pain, and laparoscopic adhesiolysis
      cures of ameliorates chronic abdominal pain in more than 80% of patients.

PMID- 9522100
TI  - [Endovascular treatment of isolated aneurysms of the hypogastric artery:
      technical considerations apropos of 2 cases].
AB  - Isolated aneurysm of the internal iliac artery is uncommon, with an incidence
      approaching 0.4%; its diagnosis is difficult; its natural course is progressive
      expansion and rupture. Two cases of hypogastric aneurysms, promptly treated with
      embolization, are reported. In selected patients the endovascular technique can
      represent a good alternative to the traditional surgical treatment that is
      associated with higher complication and mortality rate.

PMID- 9522101
TI  - Chemotherapeutic agents for human immunodeficiency virus infection: mechanism of
      action, pharmacokinetics, metabolism, and adverse reactions.
AB  - Since the mid-1980s, four new nucleoside reverse transcriptase (RT) inhibitors
      (zalcitabine, didanosine, stavudine, and lamivudine), two nonnucleoside RT
      inhibitors (nevirapine and delavirdine), and four new protease inhibitors
      (saquinavir, ritonavir, indinavir, and nelfinavir) have been approved by the US
      Food and Drug Administration for the treatment of patients with acquired
      immunodeficiency syndrome. The driving force behind the development of these new
      agents has been the increasing need for more potent agents with reduced or
      modified toxicity profiles. The purpose of this article is to review the
      absorption, distribution, metabolism, elimination, toxicities, adverse reactions,
      and mechanism of action of the currently available drugs.

PMID- 9522102
TI  - The role of clobetasol propionate emollient 0.05% in the treatment of patients
      with dry, scaly, corticosteroid-responsive dermatoses.
AB  - The use of topical corticosteroids has significantly enhanced the treatment of
      patients with dermatoses such as psoriasis and eczema. In particular, group I
      high-potency corticosteroids such as clobetasol propionate have proved safe and
      effective for limited-course treatment of inflammatory and pruritic
      manifestations of moderate-to-severe corticosteroid-responsive dermatoses. At the
      same time, much effort has gone into devising more effective strategies for
      addressing the dry skin conditions associated with various dermatologic
      disorders. An emollient added to a steroid, although not itself an active
      ingredient, can help restore the normal moisturizing process of the skin; this
      may be particularly important in soothing the discomfort of the dry skin
      conditions often encountered in moderate-to-severe dermatoses. In addition, the
      degree of epidermal hydration can affect the penetration of steroids into the
      skin. Therefore, successful outcomes in the treatment of patients with
      corticosteroid-responsive dermatoses may involve more than use of an effective
      topical steroid. This article examines a currently available cream formulation of
      0.05% clobetasol propionate containing moisturizers--emollients, dimethicone, and
      a humectant--that may contribute to improved moisture content in treated skin. A
      review of recent studies shows that clobetasol propionate emollient cream is well
      tolerated and effective in courses of up to 4 weeks for the treatment of patients
      with psoriasis or atopic dermatitis.

PMID- 9522103
TI  - Oropharyngeal candidiasis: a review of its clinical spectrum and current
      therapies.
AB  - With the increased use of antibiotics and immunosuppressive agents, oropharyngeal
      candidiasis is becoming more common. This infection is also associated with such
      advances in medical management as chemotherapy and organ transplantation and with
      human immunodeficiency virus infection. Various topical and systemic agents are
      available to treat patients with candidiasis, but optimal management can be
      elusive. Treatment of uncomplicated oropharyngeal candidiasis in the
      immunocompetent patient involves selecting a particular formulation of a topical
      medication based on oral conditions, length of contact time, and taste, texture,
      and cost of the medication. Treatment of severe oropharyngeal candidiasis,
      particularly in patients with a compromised immune system, is often more
      difficult, and relapses are common. Reports of resistance to systemic agents,
      particularly in patients needing recurrent therapy, are increasing. Amphotericin
      B, long used as an intravenous agent, is now available as an oral suspension that
      may offer therapeutic benefits comparable to those of systemic therapy without
      the toxicity associated with systemic absorption.

PMID- 9522104
TI  - Risperidone versus haloperidol: I. Meta-analysis of efficacy and safety.
AB  - Haloperidol is widely considered a reference standard in antipsychotic therapy
      and is commonly used in comparative studies of the efficacy and safety of
      antipsychotic medication. Comparative clinical trials have shown that the novel
      antipsychotic agent risperidone tends to have greater efficacy (i.e., clinical
      response defined as a > or = 20% reduction in total scores on the Positive and
      Negative Syndrome Scale) than haloperidol in patients with chronic schizophrenia
      and poses less risk of extrapyramidal symptoms (EPS). We used DerSimonian and
      Laird's random-effects model to analyze pooled patient data from available
      randomized, double-masked, comparative trials of risperidone and haloperidol in
      patients with schizophrenia treated for at least 4 weeks at recommended doses.
      The purpose of the analysis was to determine whether there are significant
      overall differences in the rates of patient clinical response, prescription of
      anticholinergic agents, and treatment dropout. Six of the nine trials revealed in
      a literature search met all criteria for inclusion in the meta-analysis. The meta
      analysis showed that in patients with chronic schizophrenia, risperidone therapy
      is associated with significantly higher response rates, significantly less
      prescribing of anticholinergic medication, and significantly lower treatment
      dropout rates than haloperidol. These results demonstrate the greater treatment
      efficacy associated with risperidone compared with haloperidol and suggest both a
      lower incidence of EPS and improved treatment compliance.

PMID- 9522106
TI  - Comparison of the skin irritation potential of two testosterone transdermal
      systems: an investigational system and a marketed product.
AB  - Effective transdermal therapy provides controlled release of the appropriate
      amount of a therapeutic agent while minimizing local irritation. Transdermal
      administration of testosterone has the potential to produce skin irritation. This
      open-label, randomized, 14-day, outpatient study compared the skin irritation of
      an investigational testosterone transdermal system (System I) with that of a
      marketed testosterone transdermal system (System II) in healthy men. In Part 1 of
      the study. System I was applied 10 times over 14 days to the same skin site on
      the backs of 26 healthy men. In Part 2, the skin irritation resulting from daily
      application of Systems I and II was assessed over 14 days in 17 men less than 65
      years of age and 16 men 65 years of age or older. At the end of Part I of the
      study, 65.4% of the subjects experienced no erythema, 15.4% of subjects had faint
      erythema, and 19.2% had moderately intense erythema immediately after System I
      removal. At the completion of Part 2, none of the System I application sites were
      assessed as having moderately intense erythema, whereas one third (33.3%) of
      System II application sites demonstrated moderately intense erythema. There were
      no differences in erythema rates between younger and older subjects with either
      transdermal system. During this study, repeated application of System I to the
      same skin site resulted in acceptable noncumulative irritation, suggesting that
      application-site rotation may not be necessary. A comparison of the two systems
      demonstrates that System I results in significantly less application-site
      irritation than does System II and that older men do not have a higher rate of
      skin reactions.

PMID- 9522105
TI  - Clinical comparison of cefaclor twice daily versus amoxicillin-clavulanate or
      erythromycin three times daily in the treatment of patients with streptococcal
      pharyngitis.
AB  - The present study was undertaken to compare the efficacy and safety of a new
      regimen of cefaclor (25 mg/kg BID) with amoxicillin-clavulanate and erythromycin
      TID at standard doses for the treatment of pediatric patients with acute
      pharyngotonsillitis (APT). A total of 673 children (age range, 2 to 12 years)
      with signs and symptoms of APT were enrolled; 245 of these children who had a
      positive throat culture for group A beta-hemolytic streptococci (GABHS) entered
      the study and were randomly assigned to receive cefaclor 25 mg/kg BID,
      amoxicillin-clavulanate 15 mg/kg TID, or erythromycin 15 mg/kg TID. A 10-day
      antibiotic course was prescribed for each patient. Clinical and bacteriologic
      responses were assessed at the end of treatment (day 10) and at the follow-up
      visit (day 30). All GABHS strains isolated from throat cultures were tested for
      in vitro sensitivity to the antibiotics used in the study. Side effects (mainly
      nausea) were rare and mild in each group and did not require discontinuation of
      therapy. No GABHS strain was resistant to cefaclor or to amoxicillin-clavulanate;
      37.9% of the strains were resistant to erythromycin. The results indicated that
      cefaclor given BID seems to be as effective as amoxicillin-clavulanate given TID
      (cure rate, 91.9% and 90.5%, respectively) and more effective than erythromycin
      given TID (cure rate, 76.8%) for the treatment of patients with APT. Erythromycin
      resistance among GABHS is an emerging problem in many geographic areas.

PMID- 9522107
TI  - Comparison of ceftibuten once daily and amoxicillin-clavulanate three times daily
      in the treatment of acute exacerbations of chronic bronchitis.
AB  - In medical practice, antibiotics are generally given empirically for the
      treatment of acute exacerbations of chronic bronchitis (AECB). To be effective,
      antibiotic therapy should be broad in spectrum, and it should also cover the
      common beta-lactamase-producing pathogens. In this multicenter, randomized,
      investigator-masked study, 469 patients with AECB were randomized (in a ratio of
      2:1) to receive 400-mg oral ceftibuten capsules once daily or 500-mg amoxicillin
      clavulanate tablets three times daily for 5 to 15 days. Patients receiving
      ceftibuten were further divided into those who took the capsule with a meal (fed)
      and those who took the capsule 1 hour before a meal (fasted). Clinical and
      microbiologic responses were evaluated after treatment at 0 to 6 days (end of
      treatment) and 7 to 21 days (follow-up). Overall clinical success was determined
      by cure/improvement of signs and symptoms of AECB at the end of treatment and at
      follow-up. Overall microbiologic assessment was graded as eradication,
      persistence, relapse, reinfection, colonization, superinfection, or unassessable.
      Tolerability was evaluated by grading observed adverse events. The mean duration
      of treatment was 10.4 days for patients who received ceftibuten and 10.1 days for
      patients who received amoxicillin-clavulanate. A total of 252 patients receiving
      ceftibuten and 117 patients receiving amoxicillin-clavulanate were evaluable for
      clinical efficacy, and 55 patients were evaluable for microbiologic response.
      Both treatments improved the signs and symptoms of bronchitis, and overall
      clinical success rates were equivalent for patients treated with ceftibuten (211
      of 252 [84%]) and amoxicillin-clavulanate (93 of 117 [79%]) (95% confidence
      interval [CI], -4.5% to 13.6%). Overall microbiologic eradication rates were also
      similar for patients treated with ceftibuten (36 of 37 [97%]) and amoxicillin
      clavulanate (12 of 14 [86%]) (95% CI, -5.2% to 21.2%). The most frequently
      reported treatment-related adverse events were gastrointestinal disturbances,
      which occurred in 15% (47 of 316) and 24% (36 of 152) of patients treated with
      ceftibuten and amoxicillin-clavulanate, respectively. No significant difference
      was observed in the ceftibutenfed and ceftibuten-fasted groups in overall
      clinical assessments of the clinical efficacy population and safety population.
      In conclusion, 400 mg oral ceftibuten once daily has a similar clinical success
      rate to 500 mg amoxicillin-clavulanate three times daily, with a trend toward
      fewer gastrointestinal side effects, in the treatment of patients with AECB.

PMID- 9522108
TI  - Effects of doxazosin in patients with mild, intermediate, and severe benign
      prostatic hyperplasia.
AB  - Traditionally, drug therapy for benign prostatic hyperplasia (BPH) has been
      reserved for patients with mild or moderate symptoms. The objective of this
      analysis was to compare responses to an alpha 1-adrenergic receptor blocker,
      doxazosin, in patients with severe, intermediate, and mild disease. Data were
      analyzed from patients with symptomatic BPH who were enrolled in two 16-week,
      double-masked, placebo-controlled studies of doxazosin. In study 1, 163
      hypertensive patients were stratified according to baseline maximum (Qmax) and
      mean (Qmean) urinary flow rate as having severe, intermediate, or mild disease.
      In study 2, 82 normotensive patients were stratified according to their baseline
      American Urological Association (AUA) BPH symptom severity score and modified
      Boyarsky symptom bothersomeness score. Overall, doxazosin was significantly more
      effective than placebo in improving Qmax and Qmean in study 1 and in improving
      the AUA-derived and modified Boyarsky scores in study 2. There were statistically
      significant differences in the response to treatment, as represented by Qmax'
      Qmean, and modified Boyarsky score, between patients with severe, intermediate,
      and mild disease. There were no significant differences in the AUA-derived scores
      of patients in the three severity groups. These results have important clinical
      implications, suggesting that the majority of BPH patients are candidates for a
      course of drug therapy, regardless of baseline disease status.

PMID- 9522109
TI  - Effect of nabumetone on hemostasis during arthroscopic knee surgery.
AB  - The known effects of commonly used nonsteroidal anti-inflammatory drugs (NSAIDs)
      on hemostatic parameters have led to concern over their use in the perioperative
      period. Nabumetone, unlike other NSAIDs, has little effect on collagen-induced
      platelet aggregation. To evaluate the effect of nabumetone 2000 mg daily on other
      hemostatic parameters (e.g., bleeding time, prothrombin time, and partial
      thromboplastin time) in the clinical setting, this double-masked study was
      conducted in patients with osteoarthritis undergoing arthroscopic knee surgery.
      After a 1-week placebo washout period, 58 patients were randomized to receive
      nabumetone and 53 were randomized to receive placebo. They were assessed before
      surgery (after 1 to 2 weeks of treatment) and again after surgery (after an
      additional 3 weeks of treatment). The study was designed to have 90% power to
      show equivalence in bleeding time to within 1.5 minutes, a difference assumed to
      be of no clinical importance. No meaningful differences were observed between the
      groups in any of the measured hemostatic parameters. Before surgery, the bleeding
      time increased by only 0.3 minutes with nabumetone and decreased by 0.2 minutes
      with placebo. The mean (+/- SD) difference between the groups in change from
      baseline was 0.5 +/- 0.3 minutes. After surgery, the changes were 0.1 minutes and
      0.0 minutes, respectively, and the difference between groups was 0.2 +/- 0.3
      minutes. These differences were neither statistically nor clinically significant,
      and maximum individual increases were similar in each group. Furthermore, there
      were no reports of abnormal bleeding in the operative knees. The results of this
      study show that nabumetone had little or no effect on hemostasis and suggest that
      this drug can be used safely in the perioperative period.

PMID- 9522110
TI  - Stimulation of glucose and amino acid transport and activation of the insulin
      signaling pathways by insulin lispro in L6 skeletal muscle cells.
AB  - The monomeric insulin analogue insulin lispro (Lys B28, Pro B29) is a rapid
      acting insulin with a shorter duration of activity than human regular insulin.
      This compound has the advantage of reducing early postprandial hyperglycemia and
      the accompanying late hypoglycemia, thereby improving overall blood glucose
      control. To date, all published studies of the functional properties of insulin
      lispro have been conducted in whole animals. This study aimed to characterize the
      cellular actions of insulin lispro and the signals it elicits in an insulin
      sensitive muscle cell line, L6 cells. Comparing the cellular actions of insulin
      lispro with those of human regular insulin, a number of observations were made.
      (1) Insulin lispro stimulated glucose and amino acid transport into L6 myotubes
      with a dose dependency and time course virtually identical to those of human
      regular insulin. (2) Insulin lispro was as effective as human regular insulin in
      stimulating time-dependent phosphorylation of insulin receptor substrate 1 (IRS
      1), p70 ribosomal S6 kinase, and two isoforms of mitogen-activated protein kinase
      (ERK1 and ERK2). (3) Insulin lispro's ability to induce the association of IRS-1
      with the p85 subunit of phosphatidylinositol 3-kinase was similar to that of
      human regular insulin. (4) As with human regular insulin, 100 nmol of the fungal
      metabolite wortmannin completely inhibited insulin lispro stimulation of glucose
      uptake. We concluded that the cellular actions of insulin lispro are similar to
      those of human regular insulin with respect to glucose and amino acid uptake and
      that the biochemical signals elicited are also comparable.

PMID- 9522111
TI  - Efficacy and tolerability of twice-daily ciprofloxacin 750 mg in the treatment of
      patients with acute exacerbations of chronic bronchitis and pneumonia.
AB  - In a review of the US Bayer ciprofloxacin (CIP) database, an analysis was
      undertaken to summarize the effectiveness and tolerability of CIP 750 mg BID in
      the treatment of patients with acute exacerbations of chronic bronchitis (AECB)
      and pneumonia. In five controlled studies, comparator (COMP) agents included
      ampicillin, intravenous cefuroxime/cefaclor, and other unspecified agents.
      Primary efficacy end points were clinical success (resolution plus improvement)
      and bacteriologic eradication at the end of therapy. The incidence of adverse
      events for CIP 750 mg BID was compared with that for COMP and with that in the
      CIP 500-mg-BID AECB and pneumonia clinical trials database. In five uncontrolled
      studies, 443 patients received CIP 750 mg BID; in 5 controlled trials comprising
      344 patients, 169 received CIP 750 mg BID and 175 received COMP. Clinical success
      for CIP was 93% (368/396) and 99% (160/162), respectively, in the uncontrolled
      and controlled studies versus 98% (156/160) for COMP agents. Corresponding
      bacteriologic eradication rates for CIP 750-mg-BID-treated patients were 77%
      (273/356) and 95% (122/128), respectively, and 77% (96/125) for COMP agents.
      Overall bacteriologic eradication by organism for CIP 750 mg BID included
      Streptococcus pneumoniae 96% (51/53), Haemophilus influenzae 98% (92/94),
      Haemophilus parainfluenzae 100% (56/56), Moraxella catarrhalis 100% (14/14; 13 of
      14 organisms were isolated in patients with AECB), and Pseudomonas aeruginosa 66%
      (135/204). Drug-related adverse events were reported in 113 (26%) CIP 750-mg-BID
      treated patients in uncontrolled trials and in 62 (37%) CIP 750-mg-BID- and 61
      (35%) COMP-treated patients in controlled trials. In the combined data from the
      CIP 750-mg-BID uncontrolled and controlled trials, adverse events occurred with
      similar frequency compared with COMP except for nausea (CIP 10%, COMP 7%) and
      diarrhea (CIP 3%, COMP 13%). In conclusion, CIP 750 mg BID provided excellent
      clinical success rates in the treatment of patients with AECB and pneumonia. CIP
      750 mg BID was well tolerated compared with the COMP agents administered.

PMID- 9522112
TI  - Potential biases in assessing the risks of pharmacotherapy due to mismeasurement
      of drug exposure.
AB  - We undertook this review to propose a minimum set of standards with which any
      evaluation of pharmacotherapy should comply, to review the evidence on which the
      relative risks of calcium channel blocker therapy for hypertension are based, and
      to evaluate published studies against these proposed standards. We selected
      English-language primary study reports published in peer-reviewed biomedical
      journals between 1995 and 1997. All the reviewed studies suffer from either
      possible misclassification of antihypertensive drug therapy, mismeasurement of
      drug exposure, or both. Given the inadequate documentation of subjects' drug
      therapy, resulting relative risk estimates cannot be substantiated.

PMID- 9522113
TI  - Costs and duration of care for lower extremity ulcers in patients with diabetes.
AB  - Medical and pharmaceutical insurance claims associated with lower extremity
      diabetic ulcers were examined retrospectively to better understand the costs and
      duration of treatment in clinical practice. The study population consisted of
      working-age individuals (18 to 64 years old) with health care benefits provided
      through private employer-sponsored insurance plans. Diagnostic information
      contained in the claims database was used to identify the severity of the ulcers,
      and the charges associated with treatment were based on claims data. Claims for
      lower extremity ulcers were found in 5.1% of individuals with diabetes. Although
      many lower extremity ulcers heal with standard treatment, some are more resistant
      to treatment and require costly ongoing medical care. Almost half of these cases
      were associated with deep infection, osteomyelitis, or amputation. Total payments
      for treatment of lower extremity ulcers in this population averaged $2687 per
      patient per year, or $4595 per ulcer episode, with inpatient expenditures
      accounting for more than 80% of these costs. Costs were significantly higher for
      patients with more severe ulcers or with inadequate vascular status in the
      affected limb. We concluded that lower extremity ulcers occur in a large number
      of working-age people with diabetes and contribute significantly to the morbidity
      associated with this disease. The high cost of treating diabetic foot ulcers
      suggested by this analysis argues for the development of better treatment
      strategies and outcomes assessments for these patients.

PMID- 9522114
TI  - A pharmacoeconomic assessment of enoxaparin and warfarin as prophylaxis for deep
      vein thrombosis in patients undergoing knee replacement surgery.
AB  - This paper examines the relative cost-effectiveness of enoxaparin and warfarin as
      prophylactic therapy for the prevention of deep vein thrombosis (DVT) in patients
      undergoing knee replacement surgery in a managed care setting. Although
      enoxaparin is more expensive than warfarin, it is also more effective in the
      prevention of DVT after knee replacement surgery. To date there has been no
      comprehensive assessment of the cost-effectiveness of the alternative agents used
      for this purpose. This evaluation is undertaken using a decision model that
      contrasts enoxaparin and warfarin regimens. The model takes explicit account of
      the incidence of proximal DVT, distal DVT, pulmonary embolism (PE), and major
      bleeds. The probabilities of clinical events are taken from data from a published
      randomized, controlled, clinical trial. Key assumptions are that PEs derive only
      from asymptomatic proximal DVTs and that a false-positive diagnosis of DVT is
      made in 10% of cases. Unit resource cost data are taken from pharmacoeconomic
      studies of DVT prophylaxis in hip replacement surgery. The analysis focuses on
      the actual or expected cost of prophylactic treatment using enoxaparin as opposed
      to warfarin and, as appropriate measures of cost-effectiveness, the cost per DVT
      event avoided and the cost per incidence of PE avoided. The expected cost of
      warfarin prophylaxis is $105 less per patient than that of enoxaparin. In terms
      of expected cost per DVT event avoided, enoxaparin prophylaxis is $2525 less than
      for warfarin; in terms of expected cost per PE avoided, it is $87,201 less.
      Enoxaparin is more cost-effective than warfarin in terms of both DVT events and
      PEs avoided in patients who have undergone knee replacement surgery.

PMID- 9522115
TI  - Risperidone versus haloperidol: II. Cost-effectiveness.
AB  - Australia and Canada are currently the only Western nations with government
      guidelines for analyzing the cost-effectiveness of drugs. We used guidelines
      issued by the Australian Pharmaceutical Benefits Advisory Committee to construct
      a model for comparing the cost-effectiveness of risperidone and haloperidol over
      a 2-year period in patients with chronic schizophrenia. Use of clozapine was also
      included in the analysis as an alternative treatment given to patients who proved
      unresponsive to therapy with haloperidol or risperidone. Results are expressed in
      Australian dollars. Cost-effectiveness was determined by using decision-analytic
      modeling to compare clinical outcomes and costs. The analytic model contained a
      decision tree for each of the compared agents that tracked the distribution of
      patients between treatment outcome pathways (i.e., scenarios). Distributions were
      based on probabilities derived from our meta-analysis results reported elsewhere
      and from other sources. Each scenario had an associated monetary cost that
      included all significant direct costs (i.e., hospital costs; outpatient costs;
      and the cost of drugs, the services of health care professionals, and government
      subsidized hostel accommodation). The cost for a given outcome was the sum of
      costs for all scenarios leading to that outcome. Cost-effectiveness was expressed
      as the total cost per favorable outcome. The definition of a favorable outcome
      was one in which the patient was in a response phase at the end of the 2-year
      period. The probability of a patient experiencing a favorable outcome at the end
      of 2 years was 78.9% for risperidone versus 58.9% for haloperidol. The total cost
      of treatment for 2 years was $15,549.00 for risperidone versus $18,332.00 for
      haloperidol. The expected cost per favorable outcome was $19,709.00 for
      risperidone and $31,104.00 for haloperidol. Risperidone was more cost-effective
      than haloperidol and therefore was "dominant" in pharmacoeconomic terms because
      it produced a higher proportion of favorable outcomes at lower cost. Sensitivity
      analysis showed that the difference in clinical response rate was a key
      determinant of cost-effectiveness.

PMID- 9522116
TI  - Sequence and gene content in 35 kb genomic clone mapping in the human Xq27.1
      region.
AB  - This paper presents detailed analysis of the entire sequence of a cosmid clone,
      26H7, containing 35 kb of human DNA. This cosmid resides on the q27.1 region of
      the human X chromosome between, DXS1232 and DXS119 loci. Novel potential small
      exons were detected for which conventional gene identification strategies
      (Northern blot analysis and extensive cDNA library screening) proved to be
      inefficient. Of the standard repetitive elements we found: 8 Alu's making up 6.2%
      of the sequence; 10 MIR segments (4.1%); 5 LINE1 elements (4.8%), 3 MIR2 (1.0%);
      2 MLT (2.9%), and 1 MSTA (0.7%) representing about 20% of the total sequence. The
      overall GC content was rather low, only 42% and no CpG island was detected using
      rare restriction enzymes. However, a CpG-rich region was identified. Computer
      aided analysis of the sequence inferred the presence of three possible genes: one
      of them was found to be homologous to the U7 RNA family elements; a second is
      reported in this paper, however at the moment no significant homology has been
      found in the data bank. The third predicted gene has not as yet been found to be
      detectable by RT-PCR. We also report in this paper the identification of X
      chromosome specific repeated sequences.

PMID- 9522118
TI  - MIRs are present in coding regions of human genes.
AB  - By using a weighted function and the method of enlarged similarity a search has
      been performed to identify mammalian interspersed repeats (MIRs) in DNA sequences
      from the EMBL data bank. The existence of MIRs is shown in coding regions of
      human genes and also in chicken and duck genomes. It is possible to conclude from
      the results obtained that MIRs were established in the coding regions of some
      genes and may have taken part in gene evolution. Furthermore, MIRs may have been
      amplified in vertebrate genomes before the origin of mammals.

PMID- 9522117
TI  - Gene identification and classification in the Synechocystis genomic sequence by
      recursive gene mark analysis.
AB  - The GeneMark method has proven to be an efficient gene-finding tool for the
      analysis of prokaryotic genomic sequence data. We have developed a procedure of
      deriving and utilizing several GeneMark models in order to get better gene
      detection performance. Upon applying this procedure to the 1.0 Mb contiguous DNA
      sequence of Synechocystis sp. strain PCC6803, we were able to cluster predicted
      genes into distinct classes and to produce the class-specific GeneMark models
      reflecting statistical characteristics of each gene class. One gene class
      apparently includes genes of exogenous origin. Using class-specific models
      reduces the gene under prediction error rate down to 1.7% in comparison with 8.1%
      reported in the previous study when only one GeneMark model was used.

PMID- 9522119
TI  - Molecular cloning and sequence of the ovine gastrin gene.
AB  - A clone encoding ovine preprogastrin was isolated from a sheep genomic library.
      The deduced 104 amino acid sequence of ovine preprogastrin was 92% and 68%
      identical to the sequences of bovine and human preprogastrin, respectively. While
      the similarity was greatest in the gastrin-17 sequence, and unexpected similarity
      was also observed in the N-terminus of mature progastrin.

PMID- 9522120
TI  - Complete genomic sequence of the human PK-L/R-gene includes four intragenic
      polymorphisms defining different haplotype backgrounds of normal and mutant PK
      genes.
AB  - The human pyruvate kinase L/R-gene has been completely sequenced in unrelated
      normal individuals and in pyruvate kinase-deficient patients by a PCR-based
      direct genomic sequencing approach and analyzed for polymorphisms. The total
      length of the gene is 8409 nucleotides. Four polymorphic sites have been
      detected: C/A1705 and C/T1992 in exon 12, a T-stretch in intron 1 occurring in
      the two polymorphic forms (T)10 and (T)19 and an (ATT)n microsatellite in intron
      J which has been found in the variation (ATT)11-17. Haplotype analysis using
      these four markers has been applied to trace the genetic background in PK
      deficiencies. The results support the idea of a single origin of most of the
      individual PK-mutations.

PMID- 9522121
TI  - Tissue-specific distribution of mouse casein kinase I alpha mRNA.
AB  - A clone isolated from a mouse skeletal muscle cDNA library by differentially
      screening for sequences expressed in skeletal but not cardiac muscle was found to
      correspond to the a-isoform of casein kinase I. The bulk of the clone
      corresponded to the 3'-untranslated region of the mRNA, which is isoform
      specific. Hybridization to mRNA indicated a tissue-specific distribution for this
      isoform of casein kinase I.

PMID- 9522122
TI  - Nucleotide and amino acid sequence analysis of the 100K protein of a serotype 3
      porcine adenovirus.
AB  - The genomic region between map units 69 and 78 of a type 3 porcine adenovirus
      (PAV3) was sequenced and analysed. An open reading frame (ORF) of 2514
      nucleotides encoding a polypeptide of 838 amino acids and approximately 94.1 kDa
      was found. The size and location of the ORF suggested it was the PAV3 homologue
      of the 100K gene and this was confirmed by nucleotide sequence comparison with
      the 100K of human adenovirus type 2. Amino acid sequence alignment of the
      predicted polypeptide with the sequences of the 100K proteins of four human
      adenoviruses and type 10 fowl adenovirus revealed sequence identities of between
      31% and 52%. Although amino acid conservation was present throughout the entire
      sequences compared, lower identity was noted in both the amino- and carboxy
      termini.

PMID- 9522123
TI  - Nucleotide sequences of the proA and proB genes of Treponema pallidum, the
      syphilis agent.
AB  - The nucleotide sequences of the putative proA and proB genes of Treponema
      pallidum were determined. The proA gene is 1287 nucleotides long and encodes a
      428 amino acid protein with a predicted M(r) of 46.6 kDa. The proB gene is 891
      nucleotides long and encodes a 296 amino acid protein with a predicted M(r) of
      31.3 kDa. The deduced amino acid sequences of the treponemal ProA and ProB
      proteins have a high degree of homology to the amino acid sequences of several
      bacterial ProA and ProB proteins. The order of the T. pallidum pro genes
      (proA/proB) is unique in comparison to the order of these genes in other
      bacteria. The identification of the putative proA and proB genes in T. pallidum,
      coupled with the previous identification of the proC gene, strongly suggests that
      this fastidious spirochete is capable of proline biosynthesis.

PMID- 9522124
TI  - Genomic structure of human cystatin A.
AB  - Cystatin A is a cysteine proteinase inhibitor with a molecular mass of 11 kDa,
      and is located mainly in the keratohyaline granules of the stratum granulosum and
      the cornified envelope of the stratum corneum in the epidermis. In this study, we
      demonstrated the genomic structure of this proteinase inhibitor in which there
      were three exons of 111 bp, 102 bp and 226 bp in length, while the lengths of the
      1st and 2nd intron were approximately 14 Kbp and 4 Kbp, respectively. The
      conserved sequence of QVVAG was encoded in the 2nd exon and was not inserted by
      any introns. There were binding sites for SP-1 and AP-2 in the promoter region
      and an AP-1 binding site in the 1st intron. The successful amplification of each
      exon of cystatin A may possibly contribute to the detection of the genomic
      abnormality of some skin disorders e.g. keratinization disorder, chronic
      bacterial infection or photophobia.

PMID- 9522125
TI  - Nucleotide and predicted peptide sequence of feline interleukin-12 (IL-12).
AB  - Feline Interleukin-12 (IL-12) is a heterodimeric glycoprotein consisting of two
      disulfide linked subunits of about 40 kD (p40) and 35 kD (p35). It is a
      pleiotropic cytokine mediating biological activities on T- and NK-cells. One
      important function is the induction of a Th1 immune response. Here we report the
      cloning and sequencing of feline IL-12, the expression of the p40-protein in E.
      coli and production of monoclonal antibodies. At the nucleotide level, feline IL
      12 shows between 87-90%, on the amino acid level between 82-87% identity to the
      bovine and human IL-12, respectively.

PMID- 9522126
TI  - Nucleotide sequence of a highly conserved region of the canine p53 tumour
      suppressor gene.
AB  - An evolutionary conserved region of the canine tumour suppressor gene, p53, was
      PCR amplified and its DNA sequence determined. The 1003 bp fragment consisted of
      exons 5 to 8 and the intervening introns. A high level of sequence homology was
      demonstrated with human sequences, with the evolutionary conserved domains II,
      III, IV and V being identical.

PMID- 9522128
TI  - Isolation and characterization of the dnaKJ operon from Actinobacillus
      actinomycetemcomitans.
AB  - The dnaKJ operon of Actinobacillus actinomycetemcomitans Y4 was cloned by the DNA
      probing method using synthetic oligonucleotides designed on the basis of two
      conserved regions in DnaK/hsp70 proteins and sequenced by inverse PCR. The
      sequenced region was shown to contain two open reading frames coding for proteins
      analogous to DnaK and DnaJ.

PMID- 9522130
TI  - Primary structure of Drosophila ribosomal protein L14 and identification of
      conserved protein motifs.
AB  - Determination of the primary structure of individual ribosomal proteins is
      important for understanding their functions and organization within the ribosome.
      I have sequenced a cDNA that encodes a Drosophila homolog of the rat ribosomal
      protein L14. The cDNA sequence was 601 nucleotides long, with an open reading
      frame encoding a protein of 166 amino acids. Homology searches revealed 34-38%
      sequence identity to the rat and yeast L14 ribosomal proteins. There were also
      extensive homologies to sequences in the EST database, which are likely to encode
      portions of L14. Analysis of sequence comparisons revealed several highly
      conserved regions, one of which is related to a portion of ribosomal protein L27.
      The sizes of the L14 proteins vary between different species, with most of the
      variability confined to the C-terminal region.

PMID- 9522129
TI  - The introns of the canine rod opsin gene show higher sequence homology to the
      human than to the rodent introns.
AB  - Using genomic DNA from late-onset retinal degenerate and wild type Labrador
      Retrievers as templates and canine exon-specific oligonucleotides as primers in
      polymerase chain reaction, all four introns of opsin were cloned and sequenced.
      Dot-matrix comparisons were made for human, murine and canine introns. Selected
      sequences containing either intronic or coding sequences were aligned and used
      for phylogenetic relationship analysis. The opsin gene introns are conserved
      between the human, the mouse and the dog with regards to number and length. In
      addition there is an astonishingly high degree of sequence homology between the
      second and fourth introns. Introns 2(1277 bp in dog) and 4 (863 bp in dog) are
      72% and 71% homologous to the human introns, and 57% and 52% homologous to the
      mouse introns, respectively. The coding sequence (CDS) of the dog shows 93%
      homology to human CDS and 88% homology to mouse CDS. A phylogenetic analysis of
      the intronic sequences 2 and 4 confirms the higher relatedness between dog and
      human than between mouse and human opsin genes. As there are good reasons to
      believe that the primate and rodent lineages are closer to each other than to the
      Canis familiaris, there must be some functional constraints on the evolution of
      human and dog opsins.

PMID- 9522127
TI  - Characterization of two length cDNA for human MSX-2 from dental pulp-derived
      cells.
AB  - Screening of a human dental pulp cells cDNA library with mouse Msx-1 and Msx-2
      cDNA probes led to the isolation of human MSX-2. Sequence and Northern Blotting
      analysis revealed that two different type of transcripts due to the length of 3'
      untranslated region were expressed in the human dental pulp cells.

PMID- 9522131
TI  - Nucleotide sequence of grapevine (Vitis vinifera) cDNA similar to SNAP proteins.
AB  - A cDNA clone (VS1) homologous to SNAP proteins was isolated from a grapevine cDNA
      library. The cDNA insert was 1167 bp long and contained a single open reading
      frame coding for 289 amino acids. The amino acid sequence of VS1 shows similarity
      (35%-45%) to SNAP proteins from various sources.

PMID- 9522132
TI  - Estimation of arterial CO2 partial pressure by measurement of tracheal CO2 during
      high-frequency jet ventilation in patients with a laryngectomy.
AB  - Tracheal and arterial CO2 partial pressures were measured simultaneously in 27
      laryngectomized patients both while they were awake and during high-frequency jet
      ventilation. Tracheal gas was sampled during brief interruptions of high
      frequency jet ventilation. Agreement between tracheal and arterial CO2 partial
      pressures was assessed using the Bland-Altman method. The tracheal-arterial CO2
      partial pressures gradient during spontaneous breathing was significantly lower
      (P < 0.0002) than during high-frequency jet ventilation. During spontaneous
      ventilation, the bias was -0.77 kPa (95% CI = -0.99 to -0.55 kPa), and the upper
      and lower limits of agreement were 0.29 kPa (95% CI = -0.11 to -0.7 kPa) and 
      1.83 kPa (95% CI = -2.24 to -1.43 kPa). During high-frequency jet ventilation,
      the bias was -1.61 kPa (95% CI = -1.76 to -1.46 kPa), and the limits of agreement
      were -0.48 kPa (95% CI = -0.75 to -0.21 kPa) and -2.74 kPa (95% CI = -3.01 to 
      2.47 kPa). Despite the poor agreement between tracheal CO2 partial pressure and
      arterial CO2 partial pressure, it is sufficient to allow for adjustment of
      ventilator settings during jet ventilation.

PMID- 9522133
TI  - Comparison of intrathecal morphine and continuous femoral 3-in-1 block for pain
      after major knee surgery under spinal anaesthesia.
AB  - Major knee surgery is associated with moderate or severe post-operative pain.
      Intrathecal morphine and continuous femoral 3-in-1 block were compared
      prospectively in 40 patients for pain after major knee surgery under spinal
      anaesthesia, with 4 mL isobaric 0.5% bupivacaine. In a random order, 20 patients
      received preservative free morphine 0.3 mg mixed with spinal bupivacaine. In 20
      patients, following spinal anaesthesia with only bupivacaine, femoral 3-in-1
      block was performed post-operatively with 0.5% bupivacaine 2 mg kg-1. The block
      was continued via a catheter with 0.25% bupivacaine 0.1 mL h-1 kg-1 until the
      next morning (24 h after induction of spinal anaesthesia). Intramuscular
      oxycodone was given as a rescue analgesic in all patients. Two patients from the
      femoral group were excluded due to technical failure. Three patients in the
      morphine group and one patient in the femoral group did not need any additional
      oxycodone. In the morphine group on average 2.8 (range 0-7) and in the femoral
      group 3.2 (0-5) additional doses of oxycodone were needed during the 24 h
      observation period. The mean pain scores were significantly lower in the morphine
      group at 9 and 12 h into the 24-h trial. Itching was seen only in the morphine
      group (40% of the patients). Other side effects were similar in the two groups.
      All patients were satisfied with their pain therapy. Both intrathecal morphine
      and femoral 3-in-1 block alone were insufficient for the treatment of severe pain
      after major knee surgery.

PMID- 9522134
TI  - Intra-articular analgesia after arthroscopic knee surgery: comparison of three
      different regimens.
AB  - One hundred and three patients ASA grades I-II, 16-80 years of age scheduled for
      arthroscopic meniscectomy were prospectively studied, and randomly allocated to
      one of four groups: group 1 (n = 25): 0.25% bupivacaine (50 mg) intra-articular
      (IA), group 2 (n = 27): 1 mg of 0.1% preservative free morphine chloride in
      saline, group 3 (n = 26): 1 mg of 0.1% preservative free morphine chloride in
      0.25% bupivacaine and group 4 (n = 25): normal saline (0.9%). The volume given
      was always 20 mL. Ketorolac [Toradol, 30 mg intramuscularly (i.m.)] was used as
      rescue medication; analgesia was assessed using a visual analogue scale (VAS), a
      verbal rating scale (VRS), supplemental analgesic consumption post-operatively
      (SAC) and the presence of side effects. Verbal rating scale and visual analogue
      scale scores showed better pain control in group 1, 20 min after surgery, and in
      groups 1 and 2 at 4 h and 10 h as well as in the global VAS. In multifactorial
      analysis no significant differences among groups or side effects was found, pH
      analysis of the substances used showed no alterations in the basal pH range. The
      analgesic efficacy of 20 mL of bupivacaine 0.25% is similar to that of 1 mg of
      morphine in 20 mL of saline 0.9%. The morphine-bupivacaine mixture was no more
      efficacious than bupivacaine or morphine alone.

PMID- 9522135
TI  - Peri-operative dysrhythmias in patients undergoing major vascular surgery--a
      preliminary report.
AB  - The objective of this prospective study was to determine the nocturnal/diurnal
      distribution of peri-operative cardiac dysrhythmias in patients with coronary
      artery disease undergoing major vascular surgery. Eight patients with significant
      coronary artery disease undergoing major vascular surgery were studied.
      Continuous Holter monitoring was performed on each patient from approximately 1 h
      pre-operatively until 2-5 days post-operatively. Frequencies of isolated
      supraventricular and ventricular premature beats, and runs of supraventricular
      and ventricular premature beats were calculated for 6-h periods (00.00-06.00;
      06.00-12.00; 12.00-18.00; 18.00-24.00 hours). Supraventricular tachycardia
      occurred significantly more frequently between 00.00 and 06.00 hours than during
      the other 6-h periods studied in the post-operative period following major
      vascular surgery.

PMID- 9522136
TI  - Influence of acute normovolaemic haemodilution on the relation between the dose
      and response of rocuronium bromide.
AB  - The influence of acute moderate haemodilution on the relation between dose and
      response for rocuronium was evaluated in 60 adult patients, ASA grade I,
      undergoing elective plastic surgery. The patients were randomly allocated to
      either the control or the haemodilution group. Following the induction of general
      anaesthesia, the status of acute moderate haemodilution in the haemodilution
      group was achieved by draining venous blood, and intravenous infusion of lactated
      Ringer's solution, 6% dextran or gelofusine, during which the levels of
      haemoatocrit and haemoglobin dropped from 44% to 27.5% and from 148.3 to 91.3 g L
      1, respectively. Neuromuscular function was assessed mechanomyographically with
      train-of-four stimulation at the wrist every 12 s and the percentage depression
      of T1 response was used as the study parameter. The relation between dose and
      response for rocuronium in the two groups was determined by the cumulative dose
      response technique. The results showed that the dose-response curve for
      rocuronium during acute moderate haemodilution was shifted in a parallel fashion
      to the left and the potency of rocuronium was increased. There were significant
      differences in ED50, ED90 and ED95 between the two groups. The ED50, ED90 and
      ED95 of rocuronium in the haemodilution group was decreased by 28.2%, 35.4% and
      38.8%, respectively, compared with the control group.

PMID- 9522137
TI  - In vitro changes in the transparency and pH of cerebrospinal fluid caused by
      adding midazolam.
AB  - The effects of adding midazolam and bupivacaine to human cerebrospinal fluid in
      glass test tubes were examined by looking for changes in pH and a reduction in
      the transparency of the solution. Midazolam (n = 6), 0.25% bupivacaine (n = 6), 5
      mg of midazolam in 6 mL of 0.25% bupivacaine (n = 6) and 5 mg of midazolam in 10
      mL of saline (n = 6) were added to 1.5-mL samples (n = 24) of cerebrospinal fluid
      taken at the time spinal anaesthesia was begun. Transparency and pH were checked
      after each increment. Cerebrospinal pH was decreased to below 7.0 by adding more
      than 3 mg of midazolam, more than 1.9 mL of 0.25% bupivacaine or 1.3 mL of the
      mixture. Cerebrospinal transparency was decreased by adding more than 0.7 mg of
      midazolam, 1.1 mL of 0.25% bupivacaine or 0.6 mL of the mixture. Midazolam in
      saline neither decreased the pH below 7.0 nor reduced transparency. These results
      do not suggest that clinically useful doses of intrathecal or epidural midazolam
      are neurotoxic.

PMID- 9522138
TI  - Disposition of lignocaine for intravenous regional anaesthesia during day-case
      surgery.
AB  - Lignocaine is a suitable and safe agent for intravenous regional anaesthesia
      (IVRA) with rapid onset of good surgical anaesthesia. The onset time of the local
      anaesthetic action of lignocaine was 11.2 +/- 5.1 min. Satisfactory surgical
      conditions, evidenced by good sensory blockade were achieved within 20 min, and
      no additional analgesics were required. There was no trend towards a fixed
      sequence, radial, median and ulnar in the development of sensory blockade. No
      patient exhibited objective symptoms of toxicity, either local or systemic, after
      release of the tourniquet, nor were there any subjective complaints. No changes
      in blood pressure, heart rate or oxygen saturation were observed at any time
      during the procedure, or after deflation of the tourniquet. After releasing the
      tourniquet lignocaine is rapidly and biexponentially eliminated, with a t1/2a of
      4.3 +/- 2.1 min and a t1/2 beta of 79.1 +/- 31.2 min. Total body clearance was
      0.86 +/- 0.39 L min-1. Eight patients showed rapid release of lignocaine from the
      exsanguinated area. In two patients the systemic plasma concentration of
      lignocaine increased more slowly than in the remaining eight. This can be
      explained by a greater degree of lignocaine absorbtion in the tissues of the arm.
      Pharmacokinetic constants after rapid and slow absorption were calculated.

PMID- 9522139
TI  - Does neostigmine have a deleterious effect on the resistance of colonic
      anastomoses?
AB  - The aim of the present study was to evaluate the effects of neostigmine as a
      final anaesthetic manoeuvre on colonic anastomoses. A colonic anastomosis was
      constructed in 40 Sprague-Dawley rats. The animals were divided into two groups:
      (1) rats receiving intravenous saline solution (placebo); and (2) rats receiving
      an intravenous injection of neostigmine. The size of the caecum, and the
      diameters of the pre-anastomotic and post-anastomotic colon were measured during
      the operation and 4 days after surgery, when all the animals were sacrificed. At
      this time, the presence of adhesions was also investigated. Each segment
      containing an anastomosis was removed, and the bursting pressure and bursting
      wall tension were determined. Loss of caecum diameter was significantly greater
      in group 2 than in group 1 (P = 0.03). Dilatation and obstruction of the colon
      were significantly more frequent in group 1 (dilatation, P = 0.01; obstruction, P
      = 0.047). Also, consumption of water by group 2 was greater than that by group 1
      (P = 0.049). No statistically significant differences were found between the
      diameters of the colon (pre- and post-anastomosis), or with respect to general
      adhesions and adhesions to the anastomotic line. No significant differences were
      found between anastomotic resistance (determined in terms of bursting pressure
      and bursting wall tension) in the two groups. The inclusion of neostigmine in an
      anaesthetic protocol under experimental setting did not reduce the resistance of
      colonic anastomoses and did not compromise normal healing. Moreover, obstruction
      caused by peristaltic weakness might be prevented by the expulsion of stool that
      is induced by the strong contraction of the colonic smooth muscle.

PMID- 9522140
TI  - Monitoring of respiratory function before and after cardiopulmonary bypass using
      side-stream spirometry.
AB  - Pulmonary impairment is more frequent after cardiac surgery than after other
      major surgical procedures. The present study investigates whether, by using
      standard respiratory monitoring, i.e. side-stream spirometry and blood gas
      analysis, it is possible to detect changes in pulmonary function secondary to
      cardiopulmonary bypass. We investigated 18 patients undergoing elective coronary
      bypass surgery or aortic valve replacement. Cardiopulmonary bypass resulted in a
      nonsignificant increase in alveolar-arterial oxygen difference from 33.0 +/- 10.6
      kPa to 36.1 +/- 12.5 kPa and arterial to end-tidal CO2 tension difference from
      0.67 +/- 0.39 kPa to 0.79 +/- 0.54 kPa. Respiratory system resistance was
      unaltered. In contrast, dynamic compliance decreased significantly after
      cardiopulmonary bypass from 78.6 +/- 22.9 to 65.4 +/- 22.4 mL cmH2O-1 with open
      chest and from 61.0 +/- 10.2 to 51.1 +/- 17.2 mL cmH2O-1 with closed chest,
      compared with corresponding values before cardiopulmonary bypass. In conclusion,
      pulmonary gas exchange was not compromised after cardiopulmonary bypass, but a
      diminished respiratory compliance was a consistent finding, even in uncomplicated
      cardiac surgery using routine respiratory monitoring.

PMID- 9522141
TI  - Cardiovascular changes during laparoscopic cholecystectomy: a study using
      transoesophageal Doppler monitoring.
AB  - A transoesophageal Doppler cardiac output monitor was used to study the
      cardiovascular changes occurring during laparoscopic cholecystectomy in patients
      without (group A) or with (group B) a history of cardiovascular disease, i.e.
      hypertension, ischaemic heart disease or heart failure. Insufflation of the
      abdomen with carbon dioxide caused significant (P < 0.01) falls in mean cardiac
      index (17.9% in group A, 25.1% in group B) and mean stroke volume index (15.3% in
      group A, 21.2% in group B). Simultaneously, there was a significant (P < 0.05)
      increase in mean systolic blood pressure (19.4%) in group A. There were no other
      differences in the cardiovascular responses of the two groups. There was no
      correlation between systolic blood pressure and either cardiac index or stroke
      volume index. No significant complications or morbidity were associated with the
      use of the transoesophageal Doppler monitor. We conclude that the cardiovascular
      changes associated with insufflation are neither predictable by clinical
      assessment nor adequately determined by routine monitoring. We recommend the
      transoesophageal Doppler monitor for use in this situation.

PMID- 9522142
TI  - The peri-operative cytokine response in infants and young children following
      major surgery.
AB  - The peri-operative cytokine response was studied in 13 infants and young children
      undergoing major surgery. All children were anaesthetized with a combined general
      and epidural anaesthetic technique, followed by post-operative epidural analgesia
      with bupivacaine and fentanyl. Blood samples were taken before and after surgery,
      24 h post-operatively, and finally, when the children were mobilized and had
      regained gastrointestinal function. Plasma samples were analysed for tumour
      necrosis factor-alpha, interleukin-1 alpha, interleukin-1 beta, interleukin-6,
      interferon-gamma, interleukin-10 and the interleukin-1 receptor antagonist. The
      cytokine responses were highly variable. Overall, no significant changes between
      pre- and post-operative plasma concentrations were found. Tumour necrosis factor
      alpha and the interleukin-1 receptor antagonist were detectable in all children,
      and a trend towards an early increase in the interleukin-1 receptor antagonist
      levels at the end of surgery was seen. The other cytokines were only detectable
      at low concentrations among a minority of children. In conclusion, this study
      showed highly variable peri-operative cytokine responses in infants and young
      children undergoing major surgery.

PMID- 9522143
TI  - The effect of different anaesthetic agents in hearing loss following spinal
      anaesthesia.
AB  - The cause of hearing loss after spinal anaesthesia is unknown. Up until now, the
      only factor studied has been the effect of the diameter of the spinal needle on
      post-operative sensorineural hearing loss. The aim of this study was to describe
      this hearing loss and to investigate other factors influencing the degree of
      hearing loss. Two groups of 22 similar patients were studied: one group received
      6 mL prilocaine 2%; and the other received 3 mL bupivacaine 0.5%. Patients given
      prilocaine were more likely to develop hearing loss (10 out of 22) than those
      given bupivacaine (4 out of 22) (P < 0.05). The average hearing loss for speech
      frequencies was about 10 dB after prilocaine and 15 dB after bupivacaine. None of
      the patients complained of subjective hearing loss. Long-term follow-up of the
      patients was not possible.

PMID- 9522144
TI  - Comparison of respiratory effects of tramadol and pethidine.
AB  - Tramadol is a centrally acting opioid with a low affinity for mu-opioid
      receptors, which has been claimed not to depress respiration as do the classic
      opioids. The respiratory effects of intravenous (i.v.) pethidine (0.6 mg kg-1)
      and tramadol (0.6 mg kg-1) were compared in 36 ASA Grade I-II patients in a
      placebo-controlled double-blind study. After induction of anaesthesia with
      propofol followed by suxamethonium-facilitated endotracheal intubation, the
      patients spontaneously breathed halothane in 70% nitrous oxide and oxygen via a
      non-rebreathing valve. Inspiratory and expiratory oxygen, and end-tidal carbon
      dioxide concentrations (PETCO2), tidal volume (VT), minute volume of ventilation
      (MV) and respiratory rate were monitored by a side-stream spirometry at an end
      tidal halothane of 0.3%. The recordings were collected before surgery. Pethidine
      caused significant respiratory depression seen as an increase in fractional
      inspiratory-expiratory oxygen difference and PETCO2 and as a decrease in MV and
      respiratory rate. However, the effects of tramadol were similar to those of a
      placebo. Tidal volume was not affected by any study drug. In conclusion, tramadol
      0.6 mg kg-1 was shown not to be associated with respiratory depression, unlike
      equipotent dose of pethidine in this setting.

PMID- 9522145
TI  - International, multicentre, placebo-controlled study to evaluate the
      effectiveness of ondansetron vs. metoclopramide in the prevention of post
      operative nausea and vomiting.
AB  - Ondansetron 4 mg was compared with metoclopramide 10 mg for prevention of post
      operative nausea and emesis in in-patients undergoing major gynaecological
      surgery in this double-blind, randomized, placebo-controlled, multicentre study.
      A total of 1044 patients received a single intravenous (i.v.) injection of study
      medication immediately before induction of anaesthesia. Nausea and emesis were
      assessed over the 24 h post-operative period. Significantly more patients who
      received ondansetron experienced no emetic episodes (44%) compared with those who
      received metoclopramide (37%, P = 0.049) or placebo (25%, P < 0.001). No nausea
      was experienced by significantly more patients who received ondansetron (32%)
      than with patients who received metoclopramide (24%, P = 0.009) or placebo (16%,
      P < 0.001). In addition, fewer emetic episodes, less severe nausea and a reduced
      need for rescue antiemetics were also observed with ondansetron (P < 0.05 vs.
      metoclopramide and placebo). Metoclopramide and placebo-treated patients were
      also 1.5 times (95% Cl 1.5-4.2) and 2.5 times (95% Cl 1.1-2.0) more likely,
      respectively, to experience nausea post-operatively. Overall, ondansetron was the
      most effective antiemetic in this patient population.

PMID- 9522146
TI  - Local anaesthetic effects on tetrodotoxin-resistant Na+ currents in rat dorsal
      root ganglion neurones.
AB  - Besides the fast tetrodotoxin-sensitive Na+ current, small dorsal root ganglion
      neurones of rats also possess a slower tetrodotoxin-resistant Na+ current. The
      blocking effect of commonly used local anaesthetics upon the tetrodotoxin
      resistant Na+ current was investigated in the present paper. Dorsal root ganglia
      were dissected from adult rats and cells were enzymatically isolated. The whole
      cell patch clamp technique was then used to measure inward Na+ currents of small
      dorsal root ganglion neurones. Externally applied local anaesthetics reversibly
      blocked the tetrodotoxin-resistant Na+ current in a dose-dependent manner. Half
      maximal blocking concentrations for tonic block were: lignocaine, 326 microM;
      prilocaine, 253 microM; mepivacaine, 166 microM; etidocaine, 196 microM
      bupivacaine, 57 microM procaine, 518 microM benzocaine, 489 microM; tetracaine,
      21 microM; and dibucaine, 23 microM. Blocking of the current by lignocaine was
      independent of temperature. The quaternary lignocaine derivative OX-314 did not
      have any effect upon the tetrodotoxin-resistant Na+ current when applied
      externally. High concentrations of tetrodotoxin also blocked the tetrodotoxin
      resistant Na+ current with a half-maximal blocking concentration of 115 microM.
      The block by high tetrodotoxin concentrations did not compete with the lignocaine
      block, suggesting that there were two independent blocking mechanisms for the two
      substances. The tetrodotoxin-resistant Na+ currents also showed a marked
      sensitivity to phasic (use-dependent) block by local anaesthetics.

PMID- 9522147
TI  - Molecular actions of droperidol on human CNS ion channels.
AB  - The molecular effects of droperidol (C22H22FN3O2) on single sodium channels from
      the human brain were investigated using the electrophysiological planar lipid
      bilayer technique. Droperidol (0.05-0.8mM) induced a concentration dependent and
      voltage independent reduction in the time averaged single channel conductance by
      two mechanisms: a reduction in the fractional channel open time (major effect,
      approximately 90%) and a decrease in the channel amplitude (minor effect). The
      weighted computer fit of the concentration response for the combined effect curve
      yielded an EC50 of 0.68 mM droperidol and a maximal conductance block of 77%.
      These blocking effects of droperidol on CNS sodium channels occurred at a
      concentration range comparable with other specific anaesthetic compounds but far
      beyond clinical serum levels (up to 0.002 mM). Therefore in contrast with animal
      preparations (frog peripheral nerve, sodium channel) the human brain sodium
      channel is not a major target site for droperidol during clinical anaesthesia.

PMID- 9522148
TI  - Diazepam-induced Ca(2+)-channel blockade reduces hypothermia-induced
      electromechanical changes in isolated guinea pig ventricular muscle.
AB  - Calcium-channel blockers reduce the in vitro effects of hypothermia and
      benzodiazepines have been reported to reduce inward calcium flow through L-type
      cardiac-calcium channels. Thus, this study was designed to determine if diazepam
      could reduce hypothermia-induced changes in ventricular papillary muscle
      electromechanical activity. Conventional microelectrode techniques were used
      while force was recorded using a miniature force transducer. Six experimental
      groups of electrically paced papillary muscles were formed (n = 6 per group). One
      was exposed to one microM nisoldipine and four were exposed to one of four
      diazepam concentrations (0.1, 1.0, 10 or 100 microM). A final group had no drug
      and provided a time-matched control. The effects were determined at 37 degrees C
      and then at 27 degrees C. At 37 degrees C, diazepam initially increased and then
      reduced inotropy and APD90. Nisoldipine reduced both APD90 and inotropy. At 27
      degrees C, 100 microM diazepam and nisoldipine (1.0 microM) reduced the
      hypothermia-induced lengthening of APD and the increase in force. Although
      diazepam reduced the hypothermia-induced alterations, the concentration required
      to do so (100 microM) suggests that this effect has little role in clinical use.

PMID- 9522149
TI  - Neurological complaints after unsuccessful spinal anaesthesia as a manifestation
      of incipient syringomyelia.
AB  - The medical literature sometimes reports neurological complications after spinal
      or epidural anaesthesia. In a few cases, the onset of symptoms can be a sign of a
      pre-existing disease without a primary connection with regional anaesthesia. In
      the following case report, the patient complained of paraesthesias in both legs
      after a failed spinal anaesthesia, even though the needle had been placed
      intrathecally. Only neurological examination and nuclear magnetic resonance
      imaging revealed the presence of syringomyelia.

PMID- 9522150
TI  - Intracranial meningioma with progesterone positive receptors presenting in late
      pregnancy.
AB  - A 36-year-old female presented with seizures and transient dysphasia in her 31
      week of pregnancy. Neuroradiological investigations revealed a large falx
      meningioma. A decision was taken to deliver the infant and excise the tumor
      before term because of the risk of an increase in the size of the tumour and the
      risk of sinus thrombosis. Therefore, she underwent in her 32 week of pregnancy an
      elective Caesarean section followed by a craniotomy to remove the meningioma.
      There were no neonatal complications and she made an uneventful recovery. The
      final pathology report confirmed the diagnosis of meningioma with progesterone
      positive receptors.

PMID- 9522151
TI  - Horner's syndrome following low-dose epidural infusion for labour: a cautionary
      tale.
AB  - While Horner's syndrome is a rare and occasionally reported complication of
      epidural 'top-ups' administered for labour and Caesarean delivery, the case
      reported here followed a low-dose epidural infusion of bupivacaine. Low-dose
      epidural infusions have generally been regarded as a safer alternative to bolus
      doses in labour. It is also the case that close supervision is deemed unnecessary
      in some centres where the mother is receiving such an epidural infusion. This
      case is reported in order to highlight the potential dangers of a low-dose regime
      which in spite of the lack of early warning signs may be associated with a high
      block.

PMID- 9522152
TI  - A transient neurological deficit following intrathecal injection of 1% hyperbaric
      bupivacaine for unilateral spinal anaesthesia.
AB  - We describe a case of transient neurological deficit that occurred after
      unilateral spinal anaesthesia with 8 mg of 1% hyperbaric bupivacaine slowly
      injected through a 25-gauge pencil-point spinal needle. The surgery and
      anaesthesia were uneventful, but 3 days after surgery, the patient reported an
      area of hypoaesthesia over L3-L4 dermatomes of the leg which had been operated on
      (loss of pinprick sensation) without reduction in muscular strength. Sensation in
      this area returned to normal over the following 2 weeks. Prospective multicentre
      studies with a large population and a long follow-up should be performed in order
      to evaluate the incidence of this unusual side effect. However, we suggest that a
      low solution concentration should be preferred for unilateral spinal anaesthesia
      with a hyperbaric anaesthetic solution (if pencil-point needle and slow injection
      rate are employed), in order to minimize the risk of a localized high peak
      anaesthetic concentration, which might lead to a transient neurological deficit.

PMID- 9522153
TI  - Malignant hyperthermia during prolonged surgery for tumour resection.
AB  - The onset of malignant hyperthermia in a patient during a prolonged anaesthetic
      for tumour resection is described. The onset was delayed with a gradual rise in
      heart rate and PETCO2 before becoming fulminant; muscle rigidity was not a
      feature. Other aspects of the patient's condition confused the presentation,
      delayed the diagnosis and may have been involved in precipitating the event.
      However, it responded rapidly to treatment and surgery was continued. A possible
      recrudescence occurred 18 h later. Malignant hyperthermia should be considered
      early in cases of unexplained tachycardia or rising PETCO2.

PMID- 9522154
TI  - Resection of phaeochromocytoma at 16-weeks gestation.

PMID- 9522155
TI  - Cost implications of the practice of anaesthesiology.

PMID- 9522156
TI  - Cerebrospinal fluid (CSF) concentration of adenylate kinase.

PMID- 9522157
TI  - Biochemical markers of cerebral damage.

PMID- 9522158
TI  - Rodent models of global cerebral ischemia: a comparison of two-vessel occlusion
      and four-vessel occlusion.
AB  - 1. Human stroke is a complex and heterogeneous phenomenon that may defy attempts
      to develop a unitary animal model with which to address all of the relevant
      issues. 2. Focal models are regarded by many to be the approach of choice, but
      both global and focal models of cerebral ischemia can be sources of useful and
      complementary insight. 3. Of the global models, four-vessel occlusion requires a
      preparatory operative procedure that may increase the risk of extraneous factors
      confounding the response to the ischemic insult itself. The procedures are only
      partly reversible, with the vertebral arteries remaining permanently occluded. 4.
      The two-vessel occlusion model is easier to perform in a single procedure, and
      the less-intrusive surgical intervention allows greater scope for recovery
      experiments. The occlusion is fully reversible. 5. Many classes of compounds with
      therapeutic potential have been identified in the laboratory, often on the basis
      of success in one class of animal model, but translating these successes into a
      clinical context has proved singularly difficult. If, in future, compounds of
      interest are tested across a range of the available models, the likelihood of
      subsequent clinical success may be enhanced.

PMID- 9522159
TI  - Halofuginone: a novel antifibrotic therapy.
AB  - 1. Fibrosis is characterized by extracellular matrix deposition, of which
      collagen type I is the major constituent. The progressive accumulation of
      connective tissue resulted in destruction of normal tissue architecture and
      function. 2. Fibrosis is a common response to various insults or injuries and can
      be the outcome of any perturbation in the cellular function of any tissue. 3.
      Halofuginone was found to inhibit collagen alpha 1(I) gene expression and
      collagen synthesis in a variety of cell cultures including human fibroblasts
      derived from patients with excessive skin collagen type I synthesis. 4.
      Halofuginone was found to inhibit collagen alpha 1(I) gene expression and
      collagen synthesis in animal models characterized by excessive deposition of
      collagen. In these models, fibrosis was induced in various tissues such as skin,
      liver, lung, etc. Halofuginone was injected intraperitoneally, added to the
      foodstuff or applied locally. 5. Halofuginone decreased skin collagen in a
      chronic graft-versus-host disease patient. 6. The ability of extremely low
      concentrations of halofuginone to inhibit collagen alpha 1(I) synthesis
      specifically and transiently at the transcriptional level suggests that this
      material fulfills the criteria for a successful and effective anti-fibrotic
      therapy.

PMID- 9522160
TI  - Review of some actions of taurine on ion channels of cardiac muscle cells and
      others.
AB  - 1. Taurine has recently been known to protect against ischemia and heart failure.
      Taurine possesses plenty of actions on the ion channels and transports, but is
      very non-specific. 2. Taurine may directly and indirectly help to regulate the
      [Ca]i level by modulating the activity of the voltage-dependent Ca2+ channels
      (also dependent on [Ca]i/[Ca]o), by regulation of Na+ channels, and secondly via
      Na-Ca exchange and Na(+)-taurine cotransport. 3. Taurine can prevent the Ca2+
      ([Ca]o or [Ca]i)-induced cardiac functions. 4. Therefore, it seems possible that
      taurine could exert the potent cardioprotective actions even under the condition
      of low [Ca]i levels as well as under the Ca2+ overload condition. 5. The
      electrophysiological actions of taurine on cardiomyocytes, smooth muscle cells,
      and neurons from recent studies are summarized.

PMID- 9522161
TI  - Antidepressant drugs in the elderly.
AB  - 1. In this article some of the most important and tolerated drugs in the elderly
      are reviewed. 2. Tricyclic antidepressants have to be used carefully because of
      their important side effects. Nortriptyline and desipramine appear to be the best
      tolerated tricyclics in old people. 3. Second generation antidepressants are
      preferred for the elderly and those patients with heart disease as they have
      milder side effects and are less toxic in overdose. 4. MAO inhibitors are useful
      drugs in resistant forms of depression in which the above mentioned drugs have no
      efficacy and the last generation drugs (reversible MAO inhibitors), such as
      moclobemide, seem to be very successful. 5. Lithium is sometimes used especially
      to prevent recurrence of depression, even if its use is limited in old patients
      due to its side effects. 6. Psychotherapy is often used as an adjunct to
      pharmacotherapy, while electroconvulsant therapy is used only in the elderly
      patients with severe depression, high risk of suicide, or drug-resistant forms.

PMID- 9522162
TI  - Bradykinin-induced responses in a coaxial bioassay system composed of rat
      anococcygeus muscle and guinea pig trachea.
AB  - 1. Epithelium-dependent effects of bradykinin (BK) were investigated in a coaxial
      bioassay system which consisted of guinea pig trachea as donor organ and rat
      anococcygeus muscle as test tissue. 2. BK (10(-9) to 10(-5) M) produced
      concentration-dependent relaxations on the phenylephrine (3 x 10(-6) M)
      precontracted rat anococcygeus muscle mounted alone. Relaxations decreased
      significantly when muscle was mounted in epithelium-intact trachea. There was
      also a significant difference between the relaxations obtained in the muscle
      within epithelium-intact and epithelium-denuded trachea (at 10(-7) to 10(-5) M
      concentrations). 3. Capsaicin (10(-5) M) pretreatment did not change BK (10(-9)
      to 10(-5) M)-induced relaxations in each preparation compared with vehicle
      pretreatment. Indomethacin (10(-6) M) in combination with thiorphan (10(-5) M)
      and atropine (10(-6) M) did not affect the BK-induced relaxations of the muscle
      within capsaicin-pretreated epithelium-intact or denuded trachea. 4. CGS 8515 (a
      specific 5-lipoxygenase inhibitor, 10(-6) M) did not change BK (10(-5) M)-induced
      relaxation on the muscle alone, and caused an increase of BK-induced relaxation
      on the muscle within epithelium-intact trachea compared with that obtained
      without CGS 8515. 5. Results showed that epithelial or nonepithelial factors were
      capable of modulating the responsiveness of rat anococcygeus muscle to BK. The
      decreased relaxation by BK in anococcygeus muscle did not occur by the release of
      cyclooxygenase products or tachykinins from tracheal epithelium, but it may have
      occurred by the contractile action of lipoxygenase product secreted by
      nonepithelial sources. In addition, BK might stimulate the secretion of an
      epithelium-derived inhibitory factor from the trachea.

PMID- 9522163
TI  - Mediation by 5-HT2 receptors of 5-hydroxytryptamine-induced contractions of human
      placental vein.
AB  - 1. In isolated human placental chorionic vein segments, 5-hydroxytryptamine (5
      HT; 10(-8) to 5 x 10(-5) M) elicited concentration-dependent contractions with
      EC50 = 5.5 (5.2-5.7) x 10(-8) M) and Emax = 93.1 +/- 7.3% of 75 mM KCl-induced
      contraction. 2. The agonist of 5-HT2 receptors, alpha-methyl-5-hydroxytryptamine,
      and the selective agonist of 5-HT1 receptors, N,N-dipropyl-5
      carboxamidotryptamine and 5-carboxamidotryptamine, induced pronounced
      concentration-related contractions, which reached 71.1 +/- 6.0%, 53.0 +/- 5.0%
      and 75.0 +/- 7.8% at the highest dose tested, respectively. The agonist of 5-HT3
      receptor, 2-methyl-5-hydroxytryptamine, reached a maximum averaging 36.7 +/- 5.1%
      of the maximal response to KCl. 3. The 5-HT1 and 5-HT3 receptor antagonists,
      methiothepin and metoclopramide (10(-7) to 10(-6) M) did not alter the response
      to 5-HT. However, ketanserin (10(-7) to 10(-6) M), a 5-HT2 receptor antagonist,
      induced significant inhibition of the concentration-response curve to 5-HT. 4.
      Contractile responses to 5-carboxamidotryptamine and 2-methyl-5-hydroxytryptamine
      were not affected by methiothepin and metoclopramide, respectively, whereas
      ketanserin significantly attenuated the contractile response to these agonists.
      5. In conclusions, our study shows that 5-HT2 receptors mediate contraction of
      the human placental vein with no obvious role for 5-HT1-like, or 5-HT3 receptors.

PMID- 9522164
TI  - Interaction between lead acetate and morphine on antinociception in mice by
      formalin test.
AB  - 1. In this study, the effects of lead acetate on two types of pain (nociception
      and inflammation) induced by formalin and its interactions with opioid system and
      morphine-induced analgesia were examined. Male albino mice weighing 22-27 g were
      used in the experiments. 2. To study nociception, the formalin test was selected.
      Morphine was administered subcutaneously 30 min before formalin injection. Lead
      acetate treatment was administered 90 min before any injection. Comparisons
      between groups were made by analysis of variance and then by Newman-Keuls test.
      Differences with P < or = 0.05 was considered statistically significant. 3.
      Different doses of morphine induced antinociception in both phases of the
      formalin test. Lead acetate induced non-dose-dependent nociception in the early
      phase and dose-dependent analgesia in the late phase. 4. Pretreatment with lead
      acetate antagonized the effect of morphine in the early phase. In the other hand,
      the effect of lead acetate in the early phase was reduced by morphine and its
      effect eliminated in the late phase. 5. It is concluded that lead can modulate
      pain response and interact with morphine-induced antinociception. Additional
      research to find the mechanisms of these effects are suggested.

PMID- 9522165
TI  - Inhibition of human erythrocyte (Na(+)-K+)ATPase by organic hydroperoxides and
      protection by ascorbic acid and butylated hydroxytoluene.
AB  - 1. The in vitro effects of cumene hydroperoxide and t-butyl hydroperoxide on
      intact human erythrocyte membrane (Na(+)-K+)ATPase activities have been studied.
      2. (Na(+)-K+)ATPase activities on erythrocyte membranes decreased in agreement
      with the results of chemiluminescence experiments. 3. Our results demonstrated
      that the organic hydroperoxides inhibit the activity of (Na(+)-K+) ATPase enzyme
      and that the antioxidants used prevent this inhibition.

PMID- 9522166
TI  - The role of dopamine in the expression of morphine withdrawal.
AB  - 1. Both L-dopa and low doses of apomorphine potentiated withdrawal symptoms such
      as jumping, "wet dog" shakes and burrows. L-dopa reduced hypothermia and
      potentiated body weight loss, whereas apomorphine produced opposite effects. 2.
      Higher doses of apomorphine attenuated jumping and burrows but had no effect on
      "wet dog" shakes. On the other hand, and with the exception of sulpiride, all
      other dopamine (DA) antagonists produced effects opposite those of the agonists
      with regard to jumping, "wet dog" shakes and burrows. 3. In addition, DA
      antagonists reduced hypothermia and body weight loss. The effects of DA agonists
      and antagonists were investigated in mice injected with 6-hydroxydopamine (6
      OHDA) intracerebrally to examine whether DA-mediated effects are somehow linked
      to noradrenergic pathways. 4. Mice pretreated with 6-OHDA developed a higher
      degree of naloxone-induced withdrawal jumping than did untreated mice. 6-OHDA
      reversed the effects of apomorphine on "wet dog" shakes and burrows while
      abolishing those of L-dopa on all withdrawal symptoms, the only exception being
      jumping, which remained unchanged. 5. 6-OHDA also reversed the effects of
      sulpiride on all withdrawal symptoms while reversing the effects of pimozide on
      jumping, and it abolished its effect on hypothermia. 6. These findings provide
      evidence suggesting that the effects of DA agonists and antagonists are dependent
      at least partly on intact noradrenergic pathways.

PMID- 9522167
TI  - Reactive oxygen production by glutamate agonists in dissociated cerebellar cells:
      a flow cytometric study.
AB  - 1. The effect of glutamate, N-methyl-D-aspartate (NMDA) and kainate on radical
      oxygen species (ROS) production and calcium influx was studied in dissociated
      cerebellar granule cells with the use of flow cytometry. 2. Glutamate and NMDA
      induced an intracellular ROS increase by an activation of NMDA receptors. 3.
      (+)MK-801 inhibited the effect on ROS production of both agonists (IC50 values of
      1.52 +/- 0.05 and 0.71 +/- 0.02 microM, respectively). 4. (+)MK-801 inhibited the
      intracellular calcium increase induced by glutamate and NMDA, whereas 6-cyano-7
      nitroquinoxaline-2,3-dione inhibited that induced by kainate. 5. NG-Nitro-L
      arginine, but not nitrendipine, inhibited the ROS production induced by glutamate
      agonists. Consequently, nitric oxide synthase might play an important role in the
      neurotoxic process induced by excitatory amino acids.

PMID- 9522168
TI  - Antihistaminic and antiallergic properties of dextro-mequitamium iodide in upper
      and lower guinea pig airways: comparison with azelastine.
AB  - 1. The ability of dextro-mequitamium iodide (d-Meq) to antagonize bronchomotor
      and inflammatory effects mediated by histamine and antigen challenge in the upper
      or lower guinea pig airways or both and its potential activity against the
      recruitment and activation of eosinophils in the bronchial wall have been
      evaluated in comparison with azelastine. 2. In receptor-binding studies, d-Meq
      displayed a nanomolar affinity for H1 and muscarinic receptors, and it was
      endowed with potent bronchodilating properties in the nanomolar range toward
      tonic contractions induced by histamine and carbachol. 3. d-Meq (100-1,000
      nmol/guinea pig) and azelastine (100-5,000 nmol/guinea pig) administered by
      aerosol significantly inhibited histamine- and antigen-induced increases in
      insufflation pressure in sensitized animals. 4. d-Meq (1,000-6,000 nmol/kg i.v.)
      dose dependently inhibited the histamine- or antigen-induced increase in vascular
      permeability in the upper airways. 5. d-Meq was more effective against histamine
      than antigen challenge, and its potency was similar or greater than that of
      azelastine. 6. Aerosolized d-Meq (1,000 nmol/animal) reduced antigen-induced
      eosinophil accumulation in the bronchoalveolar lavage (BAL) fluid from sensitized
      guinea pigs. 7. Eosinophils recovered from the BAL fluid of antigen-challenged
      animals showed an increased chemotaxis in response to LTB4 or platelet-activating
      factor. Both d-Meq and azelastine (300 nmol/animal) reduced this increase without
      affecting direct chemotaxis induced by leukotriene B4 (LTB4). 8. These findings
      provide evidence that local administration of d-Meq might be useful in the
      treatment of allergic disorders, such as rhinitis and asthma.

PMID- 9522169
TI  - Comparative study of the effects of clozapine and clothiapine in different
      preparations of guinea pig and rat isolated organs.
AB  - 1. A study has been made to know the effects of clozapine and clothiapine on the
      responses of rat isolated vas deferens to norepinephrine, dopamine and potassium,
      those of the rat isolated uterus to serotonin and potassium, and that of guinea
      pig isolated ileum to histamine. 2. Clozapine was a noncompetitive antagonist to
      norepinephrine, dopamine, serotonin and histamine; it inhibited potassium-induced
      contraction in isolated rat uterus and vas deferens. 3. Clothiapine was a
      competitive antagonist to serotonin and a noncompetitive antagonist to
      norepinephrine, dopamine and histamine; it inhibited potassium-induced
      contractions in isolated rat uterus and vas deferens.

PMID- 9522170
TI  - Alteration of cholinergic pressor and antinociceptive responses in rats
      pretreated with the cholinergic toxin AF64A.
AB  - 1. In the present study, the pressor and antinociceptive effects of physostigmine
      and oxotremorine were investigated in rats injected with AF64A
      intracerebroventricularly. 2. Physostigmine (50-100 micrograms/kg, i.v.)-induced
      pressor responses were significantly lower in AF64A-injected rats compared with
      saline-injected animals, whereas oxotremorine (20-80 micrograms/kg, i.v.)-induced
      responses were found to be similar to those seen in the saline group. 3. The
      physostigmine (100 micrograms/kg, s.c.)-induced antinociceptive effect was
      totally abolished by AF64A treatment, but that of oxotremorine (30 micrograms/kg,
      s.c.) remained unchanged at the tail-flick test. 4. The results of this study
      present functional evidence for AF64A-produced substantial loss of cholinergic
      neurons involved in the regulation of blood pressure and nociception but not in
      postsynaptic muscarinic receptors.

PMID- 9522171
TI  - Neuroactive steroids modulate in vitro the Mg(2+)-dependent Ca(2+)-ATPase
      activity in cultured rat neurons.
AB  - 1. The in vitro effect of neuroactive steroids on the Mg(2+)-dependent Ca(2+)
      ATPase activity in neuronal membranes isolated from primary cell culture of rat
      cortex was examined. 2. A 1-hr treatment of neuronal cell culture with 17-beta
      estradiol (10 pM) and pregnenolone sulfate (1 microM) resulted in an increase in
      the enzyme activity of as much as 130% and 160%, respectively. 3. Neuroactive
      steroids moderately decreased the stimulation of the Mg(2+)-dependent Ca(2+)
      ATPase activity by 72 nM calmodulin, by 20-30%. 4. The effects of hormones on the
      ATPase activity were irreversible after extensive washing of the membranes. 5.
      These results suggest that 17-beta-estradiol and pregnenolone sulfate at
      physiological concentrations could participate in the regulation of neuronal
      calcium homeostasis at a membrane level.

PMID- 9522172
TI  - Effects of NIK-247 and tacrine on muscarinic receptor subtypes in rats.
AB  - 1. The purpose of this study was to compare the effect of NIK-247 on muscarinic
      receptor subtypes with that of tacrine (THA) in rats. 2. NIK-247 and tacrine dose
      dependently inhibited the binding of [3H]pirenzepine (M1), [3H]AF-DX 384 (M2),
      and [3H]4-DAMP (M3). The IC50 values for NIK-247 were 4.4 x 10(-6) M, 1.1 x 10(
      5) M, and 1.5 x 10(-5) M, respectively, whereas those for tacrine were 5.8 x 10(
      7) M, 2.0 x 10(-6) M, and 5.8 x 10(-6) M, respectively. 3. Gpp[NH]p, a GTP
      analogue, slightly shifted the curve of displacement of [3H]AF-DX. 384 binding
      for NIK-247 to the right. However, Gpp[NH]p did not shift the curve of
      displacement of [3H]pirenzepine and [3H]4-DAMP binding to the right. 4. NIK-247
      moderately decreased the rate of beating in right atrial preparations, but did
      not decrease it below 50% of control level. 5. These findings indicate that NIK
      247 is an M1 antagonist, M2 partial agonist, and M3 antagonist.

PMID- 9522173
TI  - Cellular and molecular mechanisms of nitric oxide-induced heart muscle
      relaxation.
AB  - 1. The nitric oxide (NO) donor S-nitro-N-acetyl-penicillamine (SNAP) inhibits
      Helix aspersa heart activity and relaxes muscles. 2. K-free saline and ouabain
      both depress SNAP-induced relaxation in most experiments, but in a few
      preparations they either had no effect or potentiated SNAP-induced relaxation. 3.
      Na-K pump reactivation following preincubation in K-free saline leads to the
      pronounced transient relaxation of heart muscle, the magnitude of which depends
      on the duration of preincubation. 4. 0.1 mM SNAP inhibited the ouabain sensitive
      part of 86Rb uptake, which reflects Na-K pump activity. This inhibition is
      potentiated by phospholipase C. 5. SNAP increased cGMP levels in the heart. 6.
      These results indicate that SNAP-induced relaxation depends on Na and Ca
      gradients across the membrane, which suggests that Na:Ca exchange is involved in
      the mechanisms of SNAP-induced relaxation. It is postulated that SNAP elicits its
      inhibitory effect on the heart through a cGMP-dependent Na:Ca exchange.

PMID- 9522174
TI  - Isolation of tyrosylprotein sulfotransferase from rat liver.
AB  - 1. Tyrosylprotein sulfotransferase (TPST) is involved in the posttranslational
      modification of proteins and plays a critical role in the biological activity and
      secretion of proteins. A simple method has been developed to isolate the TPST
      (28% yield) from rat liver, using polyclonal anti-TPST antibodies. 2. The protein
      fractions eluted from antibody affinity column showed TPST activity and revealed
      a 50-54 kDa protein band in the silver stained SDS-polyacrylamide gels. 3. The
      enzyme exhibited optimum activity at pH 5.5 with 20 mM MnCl2. Unlike the TPST
      activity of the Golgi membrane, the activity of the purified enzyme was not
      stimulated by NaF, 5'-AMP, and Triton X-100. 4. The antibody was also used to
      study the TPST protein turnover in rat liver of animals that were given
      [35S]methionine. The TPST protein synthesis assessed by measuring initial rates
      of incorporation of [35S]methionine into TPST protein showed enzyme synthesis for
      up to 60 min. 35S-labeled TPST protein of rat liver was degraded with a half-life
      of 30 hr. 5. The immunoaffinity purification method using rat liver as an enzyme
      source appeared to be very simple, rapid, and easy to perform with significant
      enzyme recovery. Further, the antibody was also found to be useful in the study
      involving TPST protein metabolism.

PMID- 9522175
TI  - Fatty acid compositions in mucus and roe of Haruan, Channa striatus, for wound
      healing.
AB  - 1. Fatty acid profiles in the external mucus extract and roe of Channa striatus
      were determined using gas chromatography (GC). 2. The mucus samples were
      collected by inducing hypothermic stress (-20 degrees C) for about 1 hr, and the
      roe were collected from gravid females at night soon after they liberated their
      eggs in a spawning program. 3. All mucus and roe samples were freeze-dried,
      except a part of roe which was not. 4. The mucus extract contained unsaturated
      fatty acid (oleic acid, C18:1 and linoleic acid, C18:2) as a major component,
      21.25% and 22.47% of total lipid. 5. For the freeze- and nonfreeze-dried roe, the
      major components of fatty acid were somewhat similar to the mucus but with higher
      percentages: 58.56%, 26.08% and 45.76%, 20.94%. Interestingly, the nonfreeze
      dried roe contained a large proportion of arachidic acid, C20:0 (22.16%), which
      was totally absent in the freeze-dried roe samples. 6. This profiling of the
      fatty acid mucus extract and roe is useful in strengthening the earlier claims
      that haruan possesses a potential remedy for wound healing (Mat Jais et al.,
      1994). Therefore, we are discussing the possibility of getting an optimum amount
      of the essential fatty acid for wound healing from various other parts of the
      fish without sacrificing the fish.

PMID- 9522176
TI  - Hirunorms, novel hirudin-like direct thrombin inhibitors.
AB  - 1. Hirunorms are new synthetic peptides designed to interact with thrombin in a
      similar way to the natural inhibitor hirudin. 2. Hirunorms are specific and
      efficient in vitro inhibitors of thrombin activity. 3. Hirunorms are potent
      anticoagulant and antithrombotic agents in in vivo experimental models devoid of
      hemorrhagic effects at doses that are active in preventing thrombosis.

PMID- 9522177
TI  - Why tryptophan hydroxylase is difficult to purify: a reactive oxygen-derived
      species-mediated phenomenon that may be implicated in human pathology.
AB  - 1. Attempts and apparently successful procedures to obtain reasonable quantities
      of electrophoretically homogenous mammalian brain-derived tryptophan hydroxylase,
      (TPH), have been described, starting in the early 1970s. This work has been
      carried out with the primary objective to obtain specific antisera to this enzyme
      to map out serotonergic pathways in the nervous system. 2. By using a multitude
      of techniques, antisera have indeed been fabricated and employed. However, it is
      doubtful if pure, native TPH has ever been produced. Indeed, there is strong
      evidence that more than one isoform of TPH exists in the rat brain. Thus, these
      antisera are probably directed against TPH-derived polypeptides and not the
      holoenzyme(s). 3. The difficulty in the purification of TPH lies not only in its
      subjectivity to proteolysis, but more importantly in its probable capacity to
      produce superoxide leading to hydrogen perioxide formation. This, in turn, may
      undergo Fenton chemistry with iron at the active site of the protein to produce
      hydroxyl radicals that directly attack and destroy the enzyme molecule. Evidence
      for such a mechanism is presented together with possible protocols that might be
      used to produce pure stable holo TPH(s). 4. It is hypothesized that similar
      oxidative events may take place in vivo under certain conditions leading to
      pathological results. Strategies to block these events are suggested.

PMID- 9522178
TI  - Inhibitory effect of MCI-186, a free radical scavenger, on cerebral ischemia
      following rat middle cerebral artery occlusion.
AB  - 1. In this study, we investigated the effect of a radical scavenger, MCI-186 (3
      methyl-1-phenyl-2-pyrazolin-5-one), on cerebral damage induced by rat middle
      cerebral artery (MCA) occlusion, and further measured the hydroxyl radical level
      at the ischemic border zone using a microdialysis technique. 2. MCI-186, at a
      dose of 3 mg/kg per 30 min, was administered as a continuous infusion two times
      for 30 min, starting 20 min and then 80 min after Rose Bengal injection. 3. MCI
      186 significantly (P < 0.05) reduced size of cerebral damage 24 hr after MCA
      occlusion and significantly (P < 0.05) reduced hydroxyl radical level.

PMID- 9522179
TI  - M3-type muscarinic receptors predominantly mediate neurogenic quick contraction
      of bovine ciliary muscle.
AB  - 1. The present experiments were designed to investigate which subtypes of
      muscarinic receptors are involved in the neurogenic quick contraction of bovine
      ciliary muscle in connection to quick eye focal accommodation. 2. Transmural
      electrical stimulation (TES) produced a transient contraction, which was
      abolished in the presence of 3 x 10(-7) M tetrodotoxin and 10(-6) M atropine, but
      greatly augmented by 3 x 10(-7) M physostigmine. 3. The exogenously applied
      acetylcholine (ACh: 10(-9) to 3 x 10(-6) M) produced a concentration-dependent
      contraction, which was competitively antagonized by 10(-6) M atropine and
      augmented by 3 x 10(-7) M physostigmine, but unaffected by 3 x 10(-7) M
      tetrodotoxin. 4. The magnitude and time to peak of the maximal contraction
      produced by TES were significantly greater (1267.5 +/- 86.0 mg, P < 0.005) and
      shorter (9.0 +/- 0.2 sec, P < 0.005) than corresponding values (97.0 +/- 9.9 mg
      and 20.3 +/- 2.1 sec, respectively) of the phasic contraction caused by
      exogenously applied 10(-5) M ACh, at which concentration the agonist caused the
      maximal contraction. The velocity (140.6 +/- 7.8 mg/sec) of the transient
      contraction caused by TES was approximately 28-fold greater than that of the
      phasic contraction caused by ACh (5.1 +/- 0.9 mg/sec). 5. The contractions
      produced by TES were greatly attenuated by 4-diphenylacetoxy-N-methylpiperidine
      (4-DAMP) as an M3 antagonist and slightly by pirenzepine as an M1 antagonist
      (20.2 +/- 7.9% inhibition at the highest concentration), but not by methoctramine
      (MET) as an M2 antagonist. The IC50 value (-log M) for 4-DAMP was determined to
      be 7.17 +/- 0.14. 6. Scatchard plot analysis of [3H]-quinuclidinylbenzilate (QNB)
      binding revealed that the binding sites constituted a single population with a Kd
      of 31.2 +/- 0.8 pM and a Bmax of 895.5 +/- 93.2 fmol/mg protein. The activity in
      inhibiting [3H]-QNB binding was most potent with 4-DAMP (-log Ki = 7.98 +/-
      0.02), but less potent with pirenzepine (-log Ki = 6.43 +/- 0.04) and MET (-log
      Ki = 7.32 +/- 0.16). 4-DAMP was approximately 35- and 5-fold more potent than
      pirenzepine and MET in terms of -log Ki values, respectively, suggesting the
      predominant localization of M3 receptor subtypes in the bovine ciliary muscle
      membrane. 7. These results suggest that TES produces a neurogenic quick
      contraction of the bovine ciliary muscle, which would be mediated mainly by ACh
      released from the intramural nerve terminals and subsequent excitation of M3
      receptor subtypes localized on the ciliary muscle cells, and that neurogenic
      quick contraction of the ciliary muscle is possibly involved in part in eye focal
      accommodation.

PMID- 9522180
TI  - Comparison of relaxations evoked by photoactivation of NO-containing compounds
      and nitrergic nerve stimulation in 5-hydroxytryptamine- and potassium-contracted
      rat gastric fundus.
AB  - 1. The aim of the present study was to further investigate our earlier proposal
      of liberation of nitric oxide (NO) by photoactivation of molecules containing NO
      or NO2, which in turn relaxes gastric smooth muscle, and to determine whether
      presynaptic- and/or postsynaptic NO-mediated relaxation is affected differently
      by the degree of membrane depolarization in rat gastric fundus smooth muscle. 2.
      During contraction of rat gastric fundus with 5-hydroxytryptamine (5-HT, 10
      microM), low (K+, 25 mM) and high potassium (K+, 65.4 mM), relaxation responses
      to nitrergic nerve stimulation, photo-activation of caged NO compounds
      (streptozotocin [STZ], N omega-nitro-L-arginine-methylacetate [L-NAME], N omega
      nitro-D-arginine-methylacetate [D-NAME]), and sodium nitroprusside (SNP) were
      compared. 3. Nitrergic nerve (presynaptic) stimulation and photoactivation
      (postsynaptic) of all caged NO compounds produced rapid, transient and reversible
      relaxation of 5-HT and low-K(+)-contracted tissues. However, when contractions
      were induced by high K+, the relaxation induced by nerve stimulation was
      abolished, whereas relaxations induced by photoactivated NO compounds were
      significantly (P < 0.01) reduced. 4. The relaxation induced by sodium
      nitroprusside (SNP), but not papaverine, was also diminished in high-K(+)
      contracted tissues. The magnitude of photoactivated NO-induced relaxation was
      related to the amount of NO release, light intensity and concentration of
      compounds. 5. The evidence that photoactivated NO-induced relaxation is mediated
      by cGMP comes from the observation that zaprinast, but not forskolin, potentiated
      the relaxation. 6. It is concluded that rat gastric smooth muscle relaxes to
      photoactivation of NO or NO2-carrying molecules via NO, and it appears that
      degree of membrane depolarization may be a critical factor in dissociating the
      response to presynaptic- and postsynaptic NO-mediated relaxation in this muscle.

PMID- 9522181
TI  - Responsiveness of glycogen catabolism to adrenergic agonists during insulin
      induced hypoglycemia in rat livers.
AB  - 1. Insulin-induced hypoglycemia (IIH) promoted decreased responsiveness of
      hepatic glycogen catabolism to phenylephrine and isoproterenol, but not to
      glucagon and cyanide. 2. In addition, glycogen phosphorylase activity and
      glycogen levels were not affected by IIH. 3. It was concluded that hypoglycemia
      promoted changes in hepatic responsiveness to adrenergic agonists. 4. However,
      the ability of the liver to mobilize glycogen was not influenced by hypoglycemia.

PMID- 9522182
TI  - Dissimilar effects of lithium and valproic acid on GABA and glutamine
      concentrations in rat cerebrospinal fluid.
AB  - 1. This study compared the effects of the antimanic drugs, lithium and valproic
      acid, on GABA and glutamine CSF concentration and on head-shakes during
      hyponatremia. 2. Hyponatremic and normonatremic rats were treated with 2 mEq/kg
      lithium and 360 mg/kg valproic acid. Behavioral observation was conducted for 120
      min after which blood and CSF collection were performed under anesthesia. 3.
      Peritoneal dialysis with glucose induced moderate hyponatremia and doubled
      glutamine CSF concentrations. Both lithium and valproic acid significantly
      increased GABA CSF levels in normonatremic and hyponatremic animals. Valproic
      acid induced head-shakes and increased CSF glutamine concentration. 4. The
      results suggest that both antimanic drugs have similar effects on GABA, but
      lithium is preferred if the increase in glutamine concentration poses a problem,
      either in the presence or absence of hyponatremia.

PMID- 9522183
TI  - Differential effects of rANF and chronic guanabenz to presynaptic and
      postsynaptic alpha 2-adrenoceptor-mediated cardiovascular response in pithed
      rats.
AB  - 1. In normal rats, intracerebroventricular (i.c.v.) guanabenz induced a decrease
      in blood pressure (BP) and heart rate (HR), and this hypotension or bradycardia
      was not changed by rANF pretreatment (3 micrograms i.c.v.). 2. In pithed rats,
      intravenous (i.v.) guanabenz, an alpha 2-adrenoceptor agonist, produced an
      increase in mean blood pressure (MBP) in a dose-dependent manner. The pressor
      response by guanabenz was attenuated by infusion of rANF. This attenuation was
      additive when incubated in combination with yohimbine. 3. In pithed rats, the
      pressor response due to the increase of sympathetic outflow with electrical
      stimulation was partially blocked by rANF infusion or chronic guanabenz
      treatment. This reduction was not augmented by chronic guanabenz plus rANF
      treatment. 4. The inhibitory action of guanabenz in tachycardia evoked by
      electrical stimulation at the C7-T1 site was attenuated by rANF, but not by
      chronic treatment with guanabenz.

PMID- 9522184
TI  - Effects of intrathecally administered aminoglycoside antibiotics, calcium-channel
      blockers, nickel and calcium on acetic acid-induced writhing test in mice.
AB  - 1. Antinociceptive effects of intrathecally administered aminoglycoside
      antibiotics, calcium-channel blockers, nickel and calcium ions on the acetic acid
      induced writhing test in mice were examined. 2. Neomycin (0.5-20.0
      micrograms/mouse) gentamicin (5-40 micrograms/mouse), nicardipine, diltiazem and
      verapamil (0.5-80.0 micrograms/mouse) and calcium ions (0.02-1.0 mumol/mouse)
      exerted a dose-dependent antinociceptive activity on the acetic acid-induced
      writhing test. Nickel ions (2.5, 5.0 and 10.0 mumol/mouse) were found ineffective
      in this test. 3. These results suggest that N- and L-type, but not T-type,
      voltage-dependent calcium channels are implicated in the spinal processing of
      nociceptive information.

PMID- 9522185
TI  - [Ficus benjamina--the hidden allergen in the house].
AB  - The weeping fig, Ficus benjamina (Fb), is a relatively common indoor allergen.
      Many cases of perennial allergic rhinoconjunctivitis and allergic asthma caused
      by Fb hypersensitivity are not detected. These patients typically have proven
      sensitization to housedust mites and do not improve after avoidance of exposure
      (encasing) and specific immunotherapy. The number of Fb sensitizations is
      increasing in Germany, which can partly be explained by the cross-reactivity
      between Hevea brasiliensis (Hb) latex and Fb and the rapidly increasing number of
      mostly occupational latex allergies. But Fb itself is a potential sensitizer
      which is widely spread as ornamental plant in homes and offices. As relevant
      indoor allergen Fb ranks third after housedust mites and pets but before molds
      among our allergy patients. For diagnosis, prick-tests with Fb-latex seem to be
      more sensitive than in vitro-methods (RAST, CAPRAST). Fb plants should not be
      kept in the homes of atopic individuals or persons with latex (Hb) allergy.

PMID- 9522186
TI  - [Modification of stratum corneum quality by glycerin-containing external
      ointments].
AB  - The effects of glycerol are discussed in detail. Glycerol can lead to a
      transition of crystalline lipid structures within the horny layer lipids into
      liquid crystalline states. Especially if applied in oil/water-emulsions it
      improves, the hydration of the horny layers better than urea. In addition, if
      facilitates the dissolution of desmosomes within the superior layers of the horny
      layer enhancing desquamation. Furthermore, by using glycerol, the mechanical
      properties of the skin can be influenced; long term used leads to increased
      elasticity. The roughness of the horny layer is reduced, which can be explained
      by the abrasive and/or the hydrating effect. Glycerol used in o/w-emulsions also
      protects against the influence of tensides or noxious lipophilic agents.
      Presumably a flux from the base of the epidermis towards its surface triggers the
      regeneration of the barrier. Finally, glycerol can lead--similarly to urea--to an
      improvement in active agent penetration, as has been proven for hexylnicotinate.

PMID- 9522187
TI  - [Sun protection by optimally designed fabrics].
AB  - A rising incidence worldwide of skin cancer has been observed for years. A high
      cumulative exposure to UV radiation is a major factor in the development of such
      neoplasms. Suitable protective measures are therefore becoming increasingly
      important. Textiles provide simple, effective and medically safe protection
      against UV radiation. At present, however, in Europe--in contrast to Australia-
      the UV protection factor (UPF) for summer textiles is not stated. It is a largely
      unknown fact that by far not all textiles offer sufficient protection. Our goal
      was to study the factors which determine the UV transmission of fabrics and,
      based on these findings, to design materials which provide enhanced protection. A
      spectrophotometric method was used to determine the UV transmission by fabrics
      made of cotton, silk, polyester and viscose. The UV protection factors of the
      fabrics were computed on the basis of the transmission data. The UV protection
      factor is dependent on the type of fibre, yarn and surface design, weight per
      square metre, moisture content, colour, finishing method and degree of wear. To
      optimize the UV protection via textiles, a viscose yarn with a low UV
      transmission was used. This yarn makes it possible to design light-weight summer
      fabrics with optimized UV protection. This development will make it possible to
      offer clothing with high UV protection on the European marked. This clothing will
      not be more expensive than normal products, so that effective prevention should
      be more available.

PMID- 9522188
TI  - [Immunochemotherapy of malignant melanoma. Epifocal administration of
      dinitrochlorobenzene (DNCB) combined with systemic chemotherapy with dacarbazine
      (DTIC)].
AB  - We describe an immunochemotherapy for metastatic melanoma that combines epifocal
      applications of the contact sensitizer DNCB over cutaneous metastases with
      systemic DTIC treatment. 4 complete remissions and 3 partial remissions were
      achieved in 15 patients. 6 of these remissions were seen in the 7 previously
      untreated patients. The advantages of this therapy which is in particular
      interesting for dermatologists are tolerable side effects and low costs. This
      publication is designed to stimulate larger randomized trials in order to answer
      open questions.

PMID- 9522189
TI  - [Langerhans cell histiocytosis in the elderly].
AB  - Disseminated Langerhans-cell-histiocytosis (LCH) is most frequent in children at
      the age of 1-3 years, seldomly seen in adults and extremely rare in the elderly.
      The clinical course may be acute, subacute or chronic, progressive or stationary.
      Spontaneous remissions are possible, but rare. In elderly patients often the
      disease is at first limited to the skin before it becomes systemic. A 73-year-old
      female patient with chronic stationary disease of 3.5 years duration died 4 weeks
      after the acute dissemination of her LCH. At the beginning, her skin and liver
      involvement had responded to chemotherapy with etoposide. Six months later
      cutaneous relapse occurred with a more disseminated pattern involving the
      external auditory meatus. Treatment with topical nitrogen mustard followed by
      thalidomide produced marked improvement. As complications an irritation after
      topical application of nitrogen mustard and a maculo-papular exanthem after
      thalidomide were noted. No further visceral involvement was documented for one
      year. Then the patient developed acute disseminated disease and died within four
      weeks. As LCH may show a highly unpredictable course with progress and
      spontaneous remission, the prognosis is difficult. Any therapeutical procedures
      should be based on the actual state of the disease as determined by careful
      examination of the organs most commonly involved.

PMID- 9522190
TI  - [Cicatricial pemphigoid with autoantibodies to laminin 5 (epiligrin) in a patient
      with metastatic endometrial carcinoma].
AB  - A 71-year-old female patient presented with erosions of the oral, genital and
      ocular mucosa, but without skin lesions. One year prior to the onset of lesions,
      a metastatic adenocarcinoma of the endometrium had been diagnosed. In
      perilesional skin, direct immunofluorescence showed linear deposits of C3 and IgG
      along the basement membrane zone. Indirect immunofluorescence demonstrated anti
      basement membrane zone antibodies which bound exclusively to the dermal side of
      1M NaCl-split skin. In immunoprecipitation studies, the autoantibodies bound a
      set of proteins characteristic of epiligrin/laminin-5, and they specifically
      immunoblotted the alpha-subunit of this protein. These results confirmed our
      presumed diagnosis of anti-epiligrin cicatricial pemphigoid. Combined treatment
      with methylprednisolone and dapsone resulted in prompt remission, despite
      progression of her malignancy. So far, only eight patients with anti-epiligrin
      cicatricial pemphigoid have been reported worldwide. Our patient represents the
      first case from Austria and is clinically and immunopathologically similar to
      previously reported cases.

PMID- 9522191
TI  - [Granulomatous slack skin].
AB  - A 48-year-old woman developed granulomatous slack skin (GSS), one of the special
      forms of cutaneous T-cell lymphoma. The lesional skin slack with an atrophic,
      poikilodermic surface and granulomatous induration. Histopathological findings
      included epidermotropism, diffuse lymphoid cell infiltration and foreign body
      giant cells as well as granulomatous reactions from superficial to deep dermis,
      including part the subcutis. The diagnosis was established by positive results
      for rearrangement of the T-cell receptor gene. The therapeutic possibilities,
      especially with corticosteroids and monitoring the disease course by following
      serum angiotensin converting enzyme activity are discussed.

PMID- 9522192
TI  - [Acanthosis nigricans maligna. Case report and review of the literature].
AB  - More than 400 cases of acanthosis nigricans maligna (ANM) and 23 cases of "florid
      cutaneous papillomatosis" (FCP) were published. ANM is an obligatory
      paraneoplastic symptom. A 28-year old female patient with an adenocarcinoma of
      the stomach presented with ANM. We review the number and types of associated
      cancer with ANM. In most cases and adenocarcinoma of the gastrointestinal tract
      has been present. We feel that FCP is not an entity of its own but a variant of
      ANM; the literature supports this view.

PMID- 9522193
TI  - [Scleredema adultorum Buschke. Case report and review of the literature].
AB  - Scleredema adultorum of Buschke is a rare disorder of unknown aetiology. It is
      characterized by diffuse, non-pitting swelling and induration of the skin. Skin
      biopsies reveal marked thickening of the dermis due to collagenous replacement of
      the subcutis and deposition of hyaluronic acid between the collagen fibers. The
      disease classically only affects the skin. In 24 cases an associated monoclonal
      gammopathy has been detected. A 75-year-old patient had a 19-year history of
      scleredema adultorum. In addition to a monoclonal gammopathy the patient suffered
      from involvement of the tongue, pharynx and upper esophagus. Furthermore a
      polyneuropathy, ocular involvement with restricted eye movements and a sicca
      syndrome were present. The simultaneous occurrence of cutaneous scleredema with
      any one of the above mentioned symptoms has been reported before. The wide
      variety of extracutaneous manifestations of scleredema as found in our patient is
      amazing and has not been previously described.

PMID- 9522194
TI  - [Local treatment with chloramphenicol].

PMID- 9522195
TI  - [On the color black].
AB  - The colour black often has a negative symbolic connotation. However, our synopsis
      of its occurrence in dermatology, and the historical changes and sociocultural
      differences in the way it is viewed, highlight the diversity of its potential
      meaning. Unlike any other colour, black requires personal confrontation.

PMID- 9522197
TI  - [Skin diseases and genetic instability. I: Basic principles of genetic
      instability].

PMID- 9522196
TI  - [Keratosis follicularis spinulosa decalvans].

PMID- 9522198
TI  - Adolescent health and school health: it's time to meet the challenge.

PMID- 9522199
TI  - Increasing access to child mental health services for urban children and their
      caregivers.
AB  - This article presents the results of a study that evaluated the effects of two
      engagement interventions on the initial attendance and ongoing retention in child
      mental health services of 109 primarily children of color and their families.
      Both the combined intervention (telephone and first interview) and the telephone
      alone intervention were associated with significant increases in attendance at
      initial intake appointments over the usual intake procedure, but only the
      combined intervention was related to the greater ongoing use of services.
      Implications for future research and recommendations for modifying procedures in
      outpatient child mental health centers are also presented.

PMID- 9522200
TI  - Developing a social work research agenda on ethics in health care.
AB  - This article advocates greater empirical research on ethics in health care by
      social work researchers. Although an extensive theoretical literature exists,
      scant empirical research has been conducted on ethical issues by social work
      researchers since 1980, compared with physicians and other health care
      researchers. A theoretical framework is presented as a heuristic device to
      stimulate research on a range of topics, including the content and nature of
      ethical deliberations, contextual factors, and ethical outcomes. By demonstrating
      empirically that their interventions improve ethical outcomes, social work
      researchers can provide ammunition to support social work's role in ethical
      deliberations in health care settings.

PMID- 9522201
TI  - Informed consent meets managed care.
AB  - The doctrine of informed consent requires that health care providers disclose to
      patients the nature of procedures to be performed and the attendant risks,
      benefits, and alternatives. Equipped with an understanding of their options,
      patients then have the right to consent to treatment or to refuse it. Obtaining
      informed consent can be an intricate process, in part because of variations in
      patients' capacity for understanding and the complexities of health conditions.
      Managed care further complicates the procedure because structural and economic
      factors may influence providers' options and patients' choices. This article
      reviews the features of informed consent as they apply under managed care and
      addresses ways to ensure that consent is appropriately delivered under managed
      care systems.

PMID- 9522202
TI  - Against all odds: positive life experiences of people with advanced amyotrophic
      lateral sclerosis.
AB  - The study discussed in this article describes the nature of positive life
      experiences of 13 people coping exceptionally well while living with advanced
      amyotrophic lateral sclerosis (ALS), or Lou Gehrig's disease, and the resulting
      significant physical disability. The most powerful themes to emerge were the use
      of cognitive reappraisal, reframing, and intellectual stimulation as coping
      mechanisms; the development of wisdom; and the vital importance of interpersonal
      relationships. On the basis of our findings, we make suggestions for ways
      professionals can assist people with ALS and their significant others.

PMID- 9522203
TI  - Health status of homeless and marginally housed users of mental health self-help
      agencies.
AB  - The study discussed in this article investigated the health status of 310
      homeless and marginally housed people to determine the usefulness of mental
      health self-help agencies (SHAs) in addressing their physical health needs. The
      study compared self-reported health problems among SHA users with similar reports
      and clinical assessments of other homeless or marginally housed populations.
      Findings indicate that frequencies of health problems among respondents were
      similar to those of other homeless or marginally housed groups and that the study
      group had a higher prevalence of HIV infection and tuberculosis than the general
      population. Because this hard-to-reach group actively seeks SHAs, these
      organizations may be uniquely suited to health outreach, education, testing, and
      treatment.

PMID- 9522204
TI  - The linkage model for delivering mental health services in rural communities:
      benefits and challenges.
AB  - Growing recognition of the interconnections between physical and mental health
      has generated interest in finding ways to link these sectors of care. An
      interorganizational linkage model that places mental health staff within general
      health care settings potentially can improve the linkage between mental and
      general health care. This article presents the results of a study involving 28
      mental health staff placed in these arrangements in rural health centers. Staff
      identified roles, benefits, and barriers to linkages. Benefits included increased
      access and coordination and promotion of a more holistic sense of health care.
      Barriers were lack of space, differences among health disciplines, and
      administrative logistic problems. Social workers need good clinical and
      communication skills to work effectively in these programs.

PMID- 9522205
TI  - Children with HIV/AIDS and their families: a successful social work intervention
      based on the culturally specific health care model.
AB  - Health care utilization and community support are of utmost importance in
      minimizing the sociomedical problems of people with HIV/AIDS. This article
      describes a health clinic in Belle Glade, Florida, that effectively uses the
      Culturally Specific Health Care Model defined by the author in a previous
      article. The current article explains the process used to assess the immediate
      needs of children with HIV/AIDS and their families. It also explores some of the
      personal and social determinants that prevented the families from pursuing
      medical treatment at a community migrant health center after pediatricians had
      diagnosed the children as having HIV/AIDS.

PMID- 9522206
TI  - Meeting the mental health needs of incarcerated women.

PMID- 9522207
TI  - The dead end of self-determination.

PMID- 9522208
TI  - Humor debate continues.

PMID- 9522209
TI  - Current status of CD44 variant isoforms as cancer diagnostic markers.

PMID- 9522210
TI  - Expression of CD44 in premalignant and malignant Barrett's oesophagus.
AB  - AIMS: To establish the prevalence of CD44 protein expression in a large surgical
      series of Barrett's adenocarcinoma and associated preneoplastic lesions and to
      correlate this expression with clinicopathological data and prognosis. METHODS
      AND RESULTS: CD44H and variants (V4/V5, V6) expression was detected by
      immunohistochemistry in formalin-fixed, paraffin wax tissue samples of Barrett's
      mucosa (50) and Barrett's adenocarcinoma (73) obtained from surgical resections
      from 73 patients. This expression was correlated with pathological features of
      the tumour and prognosis. CD44H and V6 expression was found in 62% and 55% of
      Barrett's specialized mucosa negative for dysplasia and in 70% and 63% of
      Barrett's adenocarcinoma, respectively. CD44H and V6 expression was restricted to
      the lower part of the crypts in Barrett's specialized mucosa negative for
      dysplasia and reached the upper part of the crypts in high-grade dysplasia. A
      significant relation was found between CD44V6 expression and depth of tumour
      invasion in the oesophageal wall (P = 0.05), neoplastic vascular invasion (P =
      0.0001), neoplastic perineural invasion (P = 0.0004) and stage in Rosenberg's
      classification (P = 0.02). Cancers with CD44V6 expression had a significantly
      poorer prognosis (5-year survival: 17%) than those without (5-year survival: 44%)
      (P = 0.02) in univariate analysis. However, multivariate analysis showed that
      CD44V6 expression had no independent prognostic value when tumour invasion and
      lymph node involvement were taken as explanatory variables. CONCLUSION: CD44H and
      V6 are frequently expressed in Barrett's oesophagus. The pattern of expression
      that we observed from mucosa negative for dysplasia to adenocarcinoma suggests
      that CD44H and V6 may be involved in the carcinogenesis of Barrett's mucosa.
      CD44V6 expression in adenocarcinoma is correlated to aggressive pathological
      features.

PMID- 9522211
TI  - Partial or near-total pancreatectomy for persistent neonatal hyperinsulinaemic
      hypoglycaemia: the pathologist's role.
AB  - AIMS: To determine whether the presence of abnormal B-cell nuclei predicts the
      existence of a focal or of a diffuse form of persistent neonatal and infantile
      hyperinsulinaemic hypoglycaemia in a series of 20 infants. METHODS AND RESULTS:
      Intra-operative frozen sections were performed on small specimens from the
      pancreatic head, isthmus and tail. In 13 cases, abnormal B-cell nuclei were
      identified, but even a near-total pancreatectomy was insufficient to cure some of
      these patients, in whom no focal lesion was detected. On the other hand, abnormal
      insular B-cell nuclei were not found in seven cases; based on the results of
      selective venous catheterization, a limited resection was performed, sufficient
      to cure each patient, and a focal adenomatous hyperplasia was found in each
      resected specimen. CONCLUSIONS: Intra-operative examination of small pancreatic
      specimens taken from the different parts of the gland allows one to determine the
      type of lesion (focal or diffuse) in neonatal onset hyperinsulinaemic
      hypoglycaemia, and to decide on the most appropriate surgical treatment.

PMID- 9522213
TI  - Apoptosis is inversely related to bcl-2 but not to bax expression in salivary
      gland tumours.
AB  - AIMS: We investigated the extent of apoptosis in 55 benign and malignant salivary
      gland tumours and its association with the immunohistochemical expression of bcl
      2 and bax. METHODS AND RESULTS: Apoptosis was detected in histological sections
      by the 3'-end DNA labelling method. bcl-2 and bax protein expression was
      determined by immunohistochemistry. The frequency of apoptosis was clearly higher
      in malignant than in benign tumours. In pleomorphic adenomas and Warthin's
      tumours the average apoptotic index was 0.01% (range 0.00-0.07%) while in the
      malignant salivary gland tumours it was 0.42% (range 0.00-1.75%).
      Immunohistochemical bcl-2 expression was observed in all pleomorphic adenomas and
      Warthin's tumours and in most cases the expression was strong. In malignant
      tumours, 9/25 cases showed no expression and in the rest of the cases, apart from
      adenoid cystic carcinomas, the bcl-2 expression was often weak. There were
      significantly more cases with no or weak bcl-2 positivity in malignant than in
      benign salivary gland tumours (P = 0.001). There was a statistically significant
      association between a weak bcl-2 expression and a high frequency of apoptosis (P
      = 0.02). In contrast to bcl-2, strong bax expression was found in both benign and
      malignant tumours and was not associated with the frequency of apoptosis.
      CONCLUSIONS: The low bcl-2 expression in malignant tumours suggests that down
      regulation of its expression might contribute to their higher frequency of
      apoptosis.

PMID- 9522212
TI  - Value of a panel of antibodies to identify the primary origin of adenocarcinomas
      presenting as bladder carcinoma.
AB  - AIMS: Adenocarcinomas may arise primarily from the urinary bladder, but secondary
      involvement from adenocarcinomas arising in adjacent organs is more common. In
      the present study we tried to differentiate primary urinary bladder
      adenocarcinomas from adenocarcinomas arising from the surrounding organs, based
      on their antigen profiles in routinely processed, paraffin-embedded tissue
      specimens. We analysed the staining results using stepwise linear discriminant
      analysis. METHODS AND RESULTS: We investigated the usefulness of a panel of
      antibodies against cytokeratin 7, E48, cytokeratin 20, PSA, PSAP, CEA, vimentin,
      OC125 and HER-2/neu, to discriminate primary bladder adenocarcinoma from
      adenocarcinomas arising from the prostate, urachus, colon, cervix, ovary and
      endometrium. In the differential diagnosis with urinary bladder adenocarcinoma,
      an overall correct classification was reached for 77% and 81% of urachal and
      colonic carcinomas, respectively, using CEA, for 93% of prostatic adenocarcinomas
      using PSA, for 82% and 70% of cervical and ovarian adenocarcinomas, respectively,
      using OC125, and for 91% of endometrial adenocarcinomas using vimentin. Adding
      other antibodies did not improve the classification results for any of these
      differential diagnoses. CONCLUSIONS: For the surgical pathologist, a panel of
      antibodies consisting of CEA, PSA, OC125 and vimentin is helpful to differentiate
      primary urinary bladder adenocarcinomas from adenocarcinomas originating from
      prostate and endometrium, less helpful in differentiation with urachal carcinoma,
      and not helpful in differentiation with colonic, cervical and ovarian carcinoma.

PMID- 9522214
TI  - Apoptosis in thyroid neoplasms: relationship with p53 and bcl-2 expression.
AB  - AIM: Cell gain and loss occurs concurrently in tumours. Apoptosis may play a
      major role in determining the growth and aggressiveness of the tumours. The aim
      of this study was to investigate whether apoptosis is related to the degree of
      differentiation and expression of mutated p53 and bcl-2 in thyroid neoplasms.
      METHODS AND RESULTS: Fifty-three thyroid tumours of various histological types
      and 10 multinodular goitres were investigated semiquantitatively for the presence
      of apoptosis using a DNA end ligase method. Simultaneously, quantitative
      immunostaining was performed for bcl-2 and p53, two known regulators of
      apoptosis. No apoptosis was detected in normal thyroid tissues, multinodular
      goitres and in four follicular adenomas, all of which were positive for bcl-2. On
      the other hand, two anaplastic and one insular carcinomas showed marked increase
      in apoptosis along with intense p53 positivity and bcl-2 negativity. The majority
      of the follicular carcinomas showed results similar to that of follicular
      adenomas. No apoptosis was detected in 41% of papillary carcinomas, the majority
      of these being p53 negative and bcl-2 positive. Forty-four per cent of the
      papillary carcinomas demonstrated low apoptosis rate, with variable bcl-2
      positivity and mostly negative for p53. Fifteen per cent of papillary carcinomas
      showed a high apoptosis rate. They were p53 negative and mostly negative for bcl
      2. The differences of staining in various tumours with respect to p53, bcl-2 and
      apoptosis were statistically significant. Correlation analysis demonstrated a
      significant relationship between apoptosis and bcl-2 expression in thyroid
      tumours (P < 0.001), whereas no relationship was seen with p53. CONCLUSION: These
      data suggest that bcl-2 expression in thyroid neoplasms is related to apoptosis,
      p53 expression is associated with high grade thyroid tumours, but may not be
      important in the apoptotic pathways in all thyroid tumours.

PMID- 9522215
TI  - Histone mRNA in-situ hybridization in astrocytomas: a comparison with PCNA, MIB-1
      and mitoses in paraffin-embedded material.
AB  - AIMS: Non-isotopic histone mRNA in-situ hybridization (HmRNA NISH) allows
      detection of cells in the S phase of the cell cycle in paraffin-embedded tissue.
      The aim of this study was to evaluate the technique in measuring the
      proliferative activity of astrocytic neoplasms, and to compare the results with
      other proliferation estimates and patient survival. METHODS AND RESULTS: The
      proliferative activity of 71 routinely fixed and paraffin-embedded astrocytomas
      was studied by light microscopic HmRNA NISH, proliferating cell nuclear antigen
      (PCNA), Ki67MIB-1 and mitoses. A significant correlation was found between the
      labelling indices of histone mRNA (the percentage of histone-positive tumour
      cells: HmRNA-LI), immunohistochemical proliferation marker labelling indices
      (PCNA-LI: r = 0.64 and Ki67MIB-1-LI: r = 0.44) and mitotic indices (r = 0.45).
      The results were reproducible as judged by intra- and interobserver agreement
      (HmRNA/10 HPF (high power fields): r = 0.91 and r = 0.75, respectively, and HmRNA
      LI: r = 0.61 and r = 0.62, respectively). The fraction of the cells in the most
      active cell cycle phases, as suggested by the HmRNA/Ki67 and mitotic index/Ki67
      ratios, increased significantly with malignancy grade. In the univariate analysis
      the association of HmRNA-LI with survival was highly significant (P < 0.0001).
      Multivariate survival analysis showed that HmRNA-LI was an independent prognostic
      marker. CONCLUSIONS: Non-isotopic histone mRNA in-situ hybridization assay offers
      an alternative and reproducible method for measuring proliferative activity (S
      phase) in tumours under morphological control.

PMID- 9522217
TI  - Congenital acinar dysplasia: a rare cause of pulmonary hypoplasia.
AB  - AIMS: To describe a third case of congenital pulmonary acinar dysplasia,
      comparing its clinicopathological features with those of the two previous cases
      and with cystic adenomatoid malformations. METHODS AND RESULTS: An externally
      normal female infant was born to a 25-year-old after a normal pregnancy.
      Ventilation was not established. At autopsy the hypoplastic lungs showed
      bronchial development but no acinar development, resembling the pseudoglandular
      phase of 16 weeks gestation. As in the previous cases the infant was female, born
      at term with unaffected older sibling(s): however, no intrapulmonary
      haematopoietic tissue was identified in the present case. Cystic adenomatoid
      malformations also resemble microscopically the pseudoglandular phase but are
      focal pulmonary hyperplasias rather than generalized pulmonary hypoplasias.
      CONCLUSION: Congenital acinar dysplasia is a rare, apparently sporadic lethal
      developmental defect resulting in pulmonary hypoplasia due to failure of lung
      development beyond the pseudoglandular phase seen at 16 weeks gestation.

PMID- 9522216
TI  - Clinicopathological study of seven cases of spinal cord teratoma: a possible germ
      cell origin.
AB  - AIMS: To establish the clinical and pathological aspects of teratoma affecting
      the spinal cord. METHOD AND RESULTS: We reviewed our neurosurgical records for
      the last 15 years and found seven cases of teratoma of the spinal cord. The cases
      were reviewed clinically, radiologically and pathologically using
      immunohistochemical markers to identify various tissue components. We found that
      spinal cord teratoma is an extremely rare tumour of spinal cord affecting
      patients aged 23-47 years and of approximately equal male to female distribution.
      The terminal portions of spinal cord and intradural location of the tumour are
      common. Three cases were associated with vertebral anomaly. Most tumours showed
      benign (mature) components derived from more than one germ cell layer; one showed
      malignant adenocarcinomatous component. All cases were treated by surgical
      resection and two recurred at 6 and 10 year intervals without malignant
      transformation. CONCLUSION: Spinal cord teratoma is a rare, mainly benign tumour,
      which could be associated with vertebral anomaly. The pathogenesis of this tumour
      is controversial, possibly due to germinal cell aberration.

PMID- 9522218
TI  - Cutaneous lung tissue heterotopia.
AB  - AIMS: We describe the clinical and pathological findings of a previously
      unreported cutaneous lung tissue heterotopia in a child. CASE DETAILS: The 3-year
      old female patient developed a 8-mm secreting papule over her left scapula.
      Pathological examination revealed a lesion composed of bronchioles and alveoli
      within the subcutis and the dermis, with bronchiolar connection to the epidermis.
      Alveolar type II cells indicating full pulmonary differentiation were detected
      with a monoclonal antibody (AMH 152). CONCLUSIONS: The described features suggest
      that this lesion is a unique variant of rarely observed bronchus-like entities of
      the skin, designated as cutaneous bronchogenic cysts or cutaneous branchial cleft
      cysts.

PMID- 9522219
TI  - Alveolar soft part sarcoma: review of nine cases including two cases with unusual
      histology.
AB  - AIM: Alveolar soft part sarcoma is a very rare tumour. Nine cases are reviewed in
      order to identify new aspects of this tumour. METHODS AND RESULTS: The clinical
      course, histological, immunohistochemical and ultrastructural features of nine
      cases of alveolar soft part sarcoma were reviewed. Proliferative activity and p53
      protein accumulation were assessed immunohistochemically. The patients were aged
      between 18 and 70 years. In the cases with sufficient follow-up, survival was
      variable with two patients dying within 5 months and four alive at 4 years.
      Histologically all tumours had an alveolar component but one case also had a
      spindle component and another case had a pseudoglandular pattern. Six cases
      showed desmin immunoreactivity, one was muscle-specific actin positive, two were
      positive for S100 protein and three were positive for vimentin. MIB-1
      immunostaining was seen in up to 35% of cells. Two cases showed p53 protein
      accumulation. CONCLUSIONS: There appeared to be no correlation between short term
      survival (4 years or less) and clinical presentation, adjuvant treatment, tumour
      size, histological grade, vascular invasion by tumour, proliferative index, or
      p53 protein accumulation. Although unusual, spindle cell or pseudoglandular
      components can be seen in alveolar soft part sarcoma.

PMID- 9522220
TI  - Expression of E-cadherin, alpha-catenin and beta-catenin in normal ovarian
      surface epithelium and epithelial ovarian cancers.
AB  - AIMS: To study the expression of the epithelial adhesion molecule E-cadherin and
      its associated proteins alpha and beta catenin in paraffin sections of normal
      ovaries, benign cystadenomas and ovarian carcinomas, and in immortalized normal
      ovarian surface epithelial cells and ovarian carcinoma cells in culture. METHODS
      AND RESULTS: Immunocytochemistry was used to study expression of the proteins in
      paraffin sections and western blotting was used to determine levels of expression
      of the proteins in cell extracts. E-cadherin expression was found to be absent in
      ovarian surface epithelial cells in culture and infrequently expressed in normal
      ovarian surface epithelial cells in vivo, although apical punctate staining was
      occasionally seen. Seven of nine benign cystadenomas and 29/34 epithelial ovarian
      carcinomas showed some expression of E-cadherin, but expression was absent in
      poorly differentiated tumours. Expression of alpha and beta catenin was
      consistently detected on the lateral membranes of normal ovarian epithelium and
      benign cystadenomas. alpha and beta catenin expression was lost in 18% and 21% of
      ovarian carcinomas, respectively: other ovarian carcinomas expressed these
      proteins at a reduced level. A small number of these tumours showed a diffuse
      cytoplasmic rather than membranous staining. Reduced staining for alpha and beta
      catenin appeared to correlate with a more spindly, less adhesive morphology and
      increased invasive potential in matrigel. CONCLUSIONS: The results suggest that E
      cadherin expression is generally induced in well differentiated ovarian cancers.
      In contrast, alpha and beta catenins are consistently expressed in the normal
      ovarian surface epithelium and benign tumours, but are sometimes reduced or
      absent in ovarian carcinomas. It is likely that the catenins associate with
      membrane proteins other than E-cadherin in ovarian epithelium, and they may
      possibly function as tumour suppressors in this epithelium.

PMID- 9522221
TI  - Making sense of inhibin in ovarian tumours.

PMID- 9522222
TI  - Foci resembling olfactory neuroblastoma and craniopharyngioma are seen in
      sinonasal teratocarcinosarcomas.

PMID- 9522223
TI  - The grey area of mitotic counts in breast cancer.

PMID- 9522224
TI  - Myoepithelial carcinoma with predominance of plasmacytoid cells arising in a
      pleomorphic adenoma of the parotid gland.

PMID- 9522225
TI  - Villous adenoma of urethra associated with tubulovillous adenoma and
      adenocarcinoma of rectum.

PMID- 9522226
TI  - Ectopic thyroid tissue adjacent to the gallbladder.

PMID- 9522227
TI  - Arterial tumour embolism causing acute limb ischaemia.

PMID- 9522228
TI  - Dermatoepidemiology. III. ABC principles for a critical review of the literature.
AB  - EPIDEMIOLOGY: Is the study of disease occurrence in human populations. As a
      science, epidemiology emphasizes descriptive and analytic observation, clinical
      trial, behavioral intervention, and the practical utility of diagnostic tests.
      "Epidemiology" is derived from the Greek epi (among), demos (people), and logos
      (doctrine). CLINICAL EPIDEMIOLOGY: Is the application of epidemiologic principles
      and methods to problems arising in clinical medicine, dermatology included. For
      dermatologists, understanding this discipline is as important as mastering other
      basic sciences, such as immunology, microbiology, and dermatopathology. The
      recognization of Lyme disease is a classic work of "infectious" disease
      epidemiology. In 1972, a disease characterized by erythema chronicum migrans and
      "endemic arthritis" clustered in Lyme, Connecticut. By 1975, an infectious agent
      was suspected to be the cause of the disease. In 1977, the tick was thought to be
      the vector; in 1980, the spirochete became the prime suspect and, in 1982,
      Borrelia burgdorferi was identified as the etiologic agent. The study of
      hexachlorobenzene exposure, resulting in porphyria turcica, is an example of
      classic "chronic" disease epidemiology. The illness began in 1955 when sporadic
      cases of porphyria occurred in eastern Turkey. In 1957, the first case with
      illness resembling congenital erythropoietic porphyria was described. In
      subsequent years, over 3000 patients developed "epidemic" porphyria. The cause
      was due to the ingestion of seed wheat which had been treated with fungicides
      containing 20% hexachlorobenzene. EPIDEMIOLOGIC METHODS: For research, published
      elsewhere as Dermatoepidemiology. I., include descriptive observational study,
      analytic observational study, epidemiologic experimental study and tests for
      sensitivity, specificity, and positive/negative predictive value. Epidemiologic
      principles, instead, stress the correct interpretation of data, minimization of
      bias, and the appreciation of natural variations in collected data.

PMID- 9522229
TI  - Umbilical metastasis or Sister Mary Joseph's nodule.

PMID- 9522230
TI  - From capitation to rhinocitation.

PMID- 9522231
TI  - Long-term administration of therapeutic corticosteroids without risk of inducing
      aseptic necrosis.

PMID- 9522232
TI  - Different patterns of in vitro acantholysis in normal human skin samples
      explanted from different sites of the body.
AB  - BACKGROUND: The factors that contribute to a preferential anatomic localization
      of pemphigus lesions are not well known. In particular, the question arises as to
      whether certain skin areas may be more acantholysis-prone than others. OBJECTIVE:
      To verify whether, in pemphigus patients, a different susceptibility to
      acantholysis exists among different cutaneous regions, the technique of tissue
      cultures was used. METHODS: Normal human skin explants from two distinct anatomic
      regions (back and buttocks) of two former pemphigus patients were cultured in
      vitro in the presence of enalapril (6 mM) or cystamine (10 mM), two substances
      with a proven biochemical acantholytic effect. After 4 days of culture, the
      tissues were processed for standard histology. RESULTS: Diffuse acantholysis,
      with large intraepidermal splits, was observed in the explants taken from the
      backs of both subjects and cultured with either enalapril or cystamine. Mild to
      moderate acantholytic changes were detected in the explants taken from the
      buttocks of both subjects and cultured with either enalapril or cystamine. No
      structural changes were seen in the control cultures. CONCLUSIONS: Pemphigus
      patients present different thresholds of acantholysis in different areas of their
      bodies. This might explain, at least in part, certain preferential anatomic
      localizations of pemphigus lesions.

PMID- 9522233
TI  - The relation between nailfold bleeding and capillary microscopic abnormality in
      patients with connective tissue diseases.
AB  - BACKGROUND: Patients with connective tissue diseases, mainly scleroderma, show
      nailfold bleeding and nailfold capillary abnormality. An attempt was made to
      determine the possible relation between nailfold bleeding and nailfold capillary
      abnormality. METHODS: The correlation between nailfold bleeding and nailfold
      capillary abnormality was studied using quantitative nailfold capillary
      microscopy. RESULTS: The frequencies of nailfold bleeding in scleroderma, mixed
      connective tissue disease, dermatomyositis/polymyositis, and secondary Raynaud's
      phenomenon were significantly higher than those of normal controls. The
      distributions of abnormal values of capillary parameters in scleroderma, mixed
      connective tissue disease, dermatomyositis/polymyositis, systemic lupus
      erythematosus, primary Sjogren's syndrome, secondary Raynaud's phenomenon,
      primary Raynaud's phenomenon, and diabetes mellitus were significantly higher
      than those of normal controls. In normal controls, scleroderma, mixed connective
      tissue diseases, dermatomyositis/polymyositis, systemic lupus erythematosus,
      primary Sjogren's syndrome, primary Raynaud's phenomenon, and diabetes mellitus,
      all nailfold bleeding was observed in subjects with nailfold capillary
      abnormality. The distribution of nailfold bleeding in secondary Raynaud's
      phenomenon with abnormal values of capillary parameters was significantly higher
      than that with normal values. CONCLUSIONS: There is a close relationship between
      nailfold bleeding and nailfold capillary abnormality.

PMID- 9522234
TI  - A questionnaire study of road pavers' and roofers' work-related skin symptoms and
      bitumen exposure.
AB  - BACKGROUND: Skin contact with the components in asphalt and bitumen can lead to
      irritant and allergic contact dermatitis, but few data are available in the
      dermatologic literature on the skin symptoms caused by work with bitumen. In
      addition, working methods have changed markedly during recent decades. METHODS: A
      questionnaire was delivered to 50 roofers and 101 road pavers. The questionnaire
      dealt with skin symptoms, symptoms caused by solvent products, the use of
      personal protection, smoking, eating habits, work conditions, changing and
      cleaning of overalls, etc. RESULTS: Forty-eight per cent of the road pavers and
      58% of the roofers responded to the questionnaire. Relatively high percentages of
      work-induced skin irritation were reported by both the roofers (44%) and the road
      pavers (31%); 22% of the road pavers had dermatitis often or sometimes compared
      with 15% of the roofers. The hands, arms, face, and lower extremities were the
      most common sites affected. In addition to bitumen products, the road pavers
      considered amine adhesion-improving agents for paving and naphtha and solvents
      used in machine repairs, to be the main causes of their skin symptoms. The skin
      problems of the roofers were caused by man-made mineral fibers, cutback bitumen,
      and hot bitumen burns. CONCLUSIONS: Roofers endure greater exposure to chemicals
      than road pavers. Certain components, e.g. polycyclic aromatic hydrocarbons in
      bitumen, can be absorbed through the skin. Skin exposure should be lowered by
      keeping the tools, working clothes, shoes, and gloves clean. Overalls and gloves
      are recommended to be changed at least once a week. Water laundering is not
      sufficient in dissolving bitumen from overalls and underwear. Cleaning the skin
      with solvents or naphtha is not recommended, as they are skin irritants.

PMID- 9522235
TI  - Contact sensitization to cyanoacrylate adhesive as a cause of severe
      onychodystrophy.
AB  - BACKGROUND: The technology used for artificial nails, the chemistry of
      cyanoacrylates and the reported reactions to these products are briefly reviewed.
      MATERIALS AND METHODS: We studied three patients with prominent fingernail
      dystrophy, nail bed hyperkeratosis, fingertip eczema, and onycholysis, two of
      whom also had eczematous lesions at distant sites, ostensibly from hand transfer.
      Patch testing was performed with a standard screening tray, dried cyanoacrylate
      adhesives, and, in one case, with fingernail clippings. RESULTS: All three
      patients were prominently patch-test positive to the polymerized 2
      ethylcyanoacrylate, used as an adhesive on artificial (plastic) fingernails. One
      patient was also mildly formaldehyde sensitive, one was mildly reactive to two
      acrylate allergens, and one was extremely allergic to toluenesulfonamide
      formaldehyde resin. One patient had a positive patch test to her fingernail
      clippings 2 months after use of the adhesive was discontinued and an attempt was
      made to remove it. CONCLUSIONS: Reactions to cyanoacrylate adhesives used for
      artificial nails can cause both nail dystrophy and fingertip eczema, and may
      produce eczema elsewhere, probably from hand transfer. Persistence is likely due
      to retained polymer, which slowly degrades in the presence of water probably
      releasing antigens. Patch testing with the dried adhesive on an adhesive plaster
      seems to be reliable.

PMID- 9522236
TI  - Nevocellular nevus associated with alopecia presenting as aplasia cutis
      congenita.

PMID- 9522237
TI  - EB virus-related angiocentric T-cell lymphoma.

PMID- 9522238
TI  - Cutaneous calcinosis with transepithelial elimination in a patient with
      sarcoidosis.

PMID- 9522240
TI  - Oral-facial-digital syndrome (OFDS) type I in a patient with Werdnig-Hoffman
      disease.

PMID- 9522239
TI  - Regional ganglionar metastasis 24 years after surgical resection of a malignant
      melanoma.

PMID- 9522241
TI  - Familial occurrence of the LEOPARD syndrome.

PMID- 9522242
TI  - A comparative study of calcipotriol and anthralin for chronic plaque psoriasis in
      a day care treatment center.
AB  - Eighteen patients with symmetric plaque-type psoriasis were recruited for an
      open, controlled, bilateral half-body comparison study to evaluate the efficacy
      of calcipotriol/tar/UVB vs. anthralin/tar/UVB in a day care treatment setting. No
      patient had been on systemic antipsoriatic agents for at least 3 months prior to
      enrolment. One half-body was arbitrarily assigned to treatment with gradually
      increasing concentrations of anthralin as tolerated. The other half-body received
      calcipotriol ointment twice daily. Both sides received UVB and additional coal
      tar distillate in accordance with our standard day care regimen. Patients who
      were admitted to the day care program attended the clinic for UVB, anthralin, and
      calcipotriol on weekdays for two consecutive weeks. Anthralin was applied to
      psoriatic plaques on one side in the following fashion: anthralin 0.1% with
      salicylic acid 3% in zinc oxide paste on days 1 and 2; anthralin 0.2% with
      salicylic acid 3% in zinc oxide paste on days 3-5; anthralin 1% with salicylic
      acid 3% in hydrophilic petrolatum for 60 min on days 8-10 to thicker lesions; and
      anthralin 2% with salicylic acid 3% in hydrophilic petrolatum for 60 min on day
      11 to thicker lesions. On the contralateral side, calcipotriol ointment 0.05
      microgram/mL (Leo Pharmaceuticals, Ajax, Ontario) was applied to lesions twice
      daily. No anthralin or calcipotriol was applied on weekends. All patients applied
      coal tar oil 50% (Doak Oil Forte, Trans CanaDerm, St-Laurent, Quebec, equivalent
      to 5% coal tar distillate) with salicylic acid 5% in hydrophilic petrolatum to
      their lesions at home in the evenings and on weekends. UVB (FSX72T12 lamps,
      National Biologic Corporation, Twinsburg, Ohio) was administered twice daily on
      weekdays in increasing doses as tolerated (to erythema) prior to the application
      of the topical medications. No trial medications were applied to the face, scalp,
      or genital regions. For clinical evaluation, the standard Psoriasis Activity and
      Severity Index (PASI) score was modified by splitting the score for area under
      10%; the modified score (mPASI) for an area of coverage of 1%-4% was 0.5 and for
      an area of 5%-9% was 1. The head and neck area was excluded from the analysis
      since neither anthralin nor calcipotriol was used at these sites. Each half-body
      was considered to represent 100% in the area score determination. The maximum
      modified score for each side was 64.8 (vs. 72 in the standard PASI scoring
      system). Clinical evaluations were completed at days 0 (baseline), 3, 7, 10, and
      42. The primary end-point was day 10. On day 10, patients were asked to compare
      the calcipotriol ointment to the anthralin on a five-point scale in terms of
      efficacy and irritancy and to state their future preferred treatment modality.
      Following discharge from day care, patients were continued on outpatient UVB and
      tar treatments three times weekly and asked to return for a repeat clinical
      assessment after 4 weeks (day 42). Blood samples taken prior to treatment and at
      day 10 were analyzed for serum calcium. Comparisons of treatment efficacy were
      based on changes in the mPASI scores from onset of treatment to day 10, as well
      as on the corresponding percentage changes. Analyses were carried out using the
      Wilcoxon test. Subjective patient comparisons of effectiveness and irritancy, as
      well as patient preference, were tested for equiprobability using the chi-square
      goodness-of-fit test with an examination of the adjusted residuals.

PMID- 9522243
TI  - Topical isotretinoin vs. topical retinoic acid in the treatment of acne vulgaris.
AB  - This is a clinical, prospective, and longitudinal study comparing the efficacy
      and incidence of averse effects of topical isotretinoin against those of topical
      retinoic acid in the treatment of acne vulgaris. The 30 participants were
      recruited from the patients attending the outpatient clinic of the Department of
      Dermatology of "Dr Manuel Gea Gonzalez" General Hospital in Mexico City. They
      belonged to either sex and any race, their ages ranged between 13 and 30 years,
      and they presented with 15 to 100 facial inflammatory lesions (papulo-pustules)
      and/or 15 to 100 noninflammatory lesions (comedones) and no more than three
      nodulo-cystic lesions. The criteria of exclusion were as follows: pregnancy or
      lactation, systemic treatment with steroids, antibiotics, antiandrogens, or oral
      retinoids in the preceding 24 months, treatment with ultraviolet radiation,
      hypersensitivity to retinoids, or a severe systemic illness. From 44 interviewed
      patients, 14 were excluded. A detailed clinical history was obtained from the
      remaining individuals, the degree of seborrhea was recorded, and acne lesions
      were counted. Each patient received either isotretinoin gel 0.05% or retinoic
      acid cream 0.05%. The patients were instructed to wash their faces in the
      mornings and evenings with a neutral soap, and to apply the product after the
      evening cleansing. The patients were examined again after 2, 4, 8, and 12 weeks
      of treatment and, at each appointment, the number of lesions was recorded and the
      severity of acne was graded according to the classification of Plewig and
      Kligman. The seriousness of the adverse effects, such as stinging, pruritus,
      erythema, xerosis, and desquamation, was evaluated blindly by an investigator who
      did not know what group the patient belonged to, and graded as 1 = mild, 2 =
      moderate, and 3 = severe. The efficacy of each drug was determined by the
      reduction in the number of lesions between weeks 0 and 12 of treatment. An
      excellent response corresponded to a 76%-100% reduction of the lesions, a good
      response to a 51%-75% reduction, a fair response to a 26%-50% reduction, and a
      poor response to a 0%-25% reduction. The results were analyzed statistically
      using the chi-square test, the exact test of Fisher and the test of Wilcoxon-Mann
      Whitney. The changes in the numbers of lesions between weeks 0 and 12 were
      analyzed separately for each group of treatment, and the level of statistical
      significance was fixed at 0.05. The analysis was performed with the aid of a Stat
      program, version 4.0. RESULTS: The patients were assigned randomly to either
      Group I (isotretinoin) or Group II (retinoic acid). Each group was composed of 15
      individuals and, as a coincidence, in each group there were nine women and six
      men. The clinical differences between the groups at the first visit were not
      statistically significant. In both groups, there was, in general, a good response
      to treatment (Fig. 1). Both drugs had a similar degree of efficacy on
      inflammatory lesions. At the first visit, grades III and IV predominated,
      whereas, after 12 weeks of treatment, most patients were classified in grades I
      or II (Fig. 2). Similar results were observed regarding noninflammatory lesions
      (Fig. 3). Ten of the patients of Group II complained of stinging associated with
      the treatment, especially at weeks 8 and 12, as well as erythema and desquamation
      at the 12th week. Erythema and stinging lasted for minutes or hours, whereas
      desquamation persisted for several days. Seven individuals receiving isotretinoin
      mentioned irritation, which was of a mild degree.

PMID- 9522244
TI  - An approach to the treatment of psychogenic parasitosis.
AB  - BACKGROUND: Patients with psychogenic parasitosis typically seek help from
      nonpsychiatric physicians and can be difficult and time-consuming to treat.
      Pimozide has been promoted as the treatment of choice but is not indicated for
      every patient presenting with this symptom. Our purpose was to develop a
      realistic treatment protocol for the nonpsychiatric physician faced with these
      patients. METHODS: Using what is known about this problem through review of the
      literature and our own experience with 20 patients, a practical treatment
      strategy is suggested. RESULTS: It is proposed that dermatologists and primary
      care professionals seeing these patients determine (1) whether or not the
      patient's belief in infestation is shakable and (2) whether or not the patient is
      depressed, in order to chose a therapeutic plan. CONCLUSIONS: Dermatologists and
      psychiatrists can work together to develop treatment protocols that minimize risk
      and maximize therapy for patients with psychogenic parasitosis.

PMID- 9522245
TI  - Pharmacoeconomic analysis of topical treatments for tinea infections.
AB  - BACKGROUND: A payor-perspective economic analysis of the topical creams
      ciclopirox, clotrimazole, ketoconazole, miconazole, and terbinafine (TER) used to
      treat dermatophytosis has been made. This pharmacoeconomic evaluation was
      conducted in Austria, Germany, and Switzerland. METHODS: A four-phase approach
      was used. Phase 1: experts were assembled to identify the standard approach for
      management of fungal infections and a decision tree was constructed to model the
      process. Phase 2: meta-analysis was used to determine success, failure, and
      relapse rates. Phase 3: economic analyses performed included cost of regimen,
      total expected cost, and cost-effectiveness. Phase 4: sensitivity analyses
      (robustness analysis) were also executed to determine the validity of the
      assumptions. RESULTS: In the total expected cost analysis, TER demonstrated the
      lowest overall cost of treating patients. Terbinafine also provided the highest
      number of disease-free days during the analytic time horizon and, consequently,
      the lowest cost per disease-free day. Sensitivity analyses suggest that TER is
      the most cost-effective topical product for treating dermatophytosis in Austria,
      Germany, and Switzerland. CONCLUSIONS: All analytic scenarios suggest that TER
      therapy demonstrates lower expected costs and generates more DFDs when compared
      with the fungistatic topical therapies included in this pharmacoeconomic
      analysis. Terbinafine is expected to be the most cost-effective choice in
      Austria, Germany, and Switzerland for treatment of dermatophytosis minor.

PMID- 9522246
TI  - Osler's legacies to dermatologists.
AB  - A century ago, Dr William Osler was the best-known physician in the world.
      Although not yet Sir William, an honor bestowed in 1909, his encyclopedic
      Principles and Practice of Medicine of 1892 had been translated into many
      languages and was to see several further editions. Meanwhile, his fame as a
      teacher, speaker, essayist, educational administrator, clinical investigator,
      medical consultant par excellence, kind and wise mentor and friend, humanist,
      bibliophile and collector, practical joker, and loving family man had made him a
      legend when he was barely 40 years old. A native of Canada, who at the age of 35
      came to the United States for 21 years and then moved to England for the final 14
      years. Osler's stunning list of achievements continued until his death in 1919
      and has since become a myth in its magnitude, aided substantially by the 1925
      Pulitzer-prize-winning, huge, and adoring biography by his student and acolyte,
      Harvey Cushing. Today, dermatologists can recite the cutaneous signs of Cushing's
      disease, but may be less secure in stating (or, more importantly, identifying) a
      variety of lesions associated with Osler's name. This article reviews those
      lesions which commemorate the name and dermatologic contributions of this great
      physician. In addition, other contributions and important personal
      characteristics that justify keeping his memory alive are discussed.

PMID- 9522247
TI  - Our scabies treatment is archaic, but ivermectin has arrived.

PMID- 9522248
TI  - Ketoconazole for the treatment of tinea versicolor.

PMID- 9522249
TI  - Tethered cord associated with intraspinal lipoma and a subcutaneous abscess
      secondary to a dermal sinus.

PMID- 9522250
TI  - Spontaneous skin necrosis in alcoholic liver cirrhosis.

PMID- 9522251
TI  - The mixture distribution of left minus right hand skill in men and women.
AB  - The distribution of left minus right (L - R) hand skill (peg moving) was studied
      in 436 men and 247 women. In total sample, the distribution was continuous and a
      sum of two Gaussian curves. One of them was constituted by subjects with better
      right hand (79.0%) and better left hand (21.0%). The other curve (2.5% of total)
      was exclusively due to the subjects with better left hand. In men and women, the
      total curve was a sum of three overlapping Gaussian curves. Two of them were
      mostly due to the subjects with better right hand. There was a third curve
      representing almost entirely the subjects with better left hand. Women were more
      strongly right-handed than men. There was no significant sex difference at the
      sinistral side. The overall results were compatible with the right shift theory,
      but there was not a single Gaussian curve representing a chance distribution with
      a mean of zero. These results suggested that the distribution of manual asymmetry
      in skill is continuous, which may be described by probabilities due to subjects
      with better right and left hands; there is no place for chance in human
      handedness.

PMID- 9522252
TI  - Immunological aspects of kaolin-induced hydrocephalus.
AB  - Adult female Sprague Dawley rats were administrated 0.1 ml Kaolin (250 mg/ml)
      into cisterna magna. One, 4 and 8 weeks later, brains were analyzed using
      antibodies against MHC class I (OX18), MHC class II (OX6), CD4 (OX38), CD8 (OX8),
      OX42, ED1, NF, GFAP, AChE and TH. Remarkably high numbers of T lymphocytes, and
      OX42- and ED1-positive macrophages were found aggregated in subarachnoid spaces,
      and in the third and fourth ventricles. Marked aggregations of ED1-positive
      reactive microglial cells were also found in paraventricular structures, medial
      septum, retrosplenic cortex and commissural structures. However, no such cells
      were found in hippocampus. ED1-positive areas were also positive for round cells
      with a rim of MHC I fluorescent cytoplasm as well as for OX42-positive cells and
      MHC II positive microglial cells. At week 1, in ventro-frontal areas of cortex,
      CD8-positive cells and MHC I positive astroglial fibers were detected. At week 1,
      MHC I positive ramified microglial cells were also recognized in almost the
      entire brain. These positive cells gradually decreased with time and finally
      remained rounded with a rim of fluorescent cytoplasm. In addition, ED1 positive
      partly ramified microglial cells could be recognized in corpus callosum, probably
      representing cells in transition between ramified and reactive microglia. CD8+
      cells entered ventral brain structures, and were found in the horizontal diagonal
      band at week 4, and had disappeared at week 8. Finally in cortex, ED1 positive
      microglial cells could be identified only in the retrosplenic cortex, and there
      were also "dark shrunken neurons" in light microscopic stainings. However, there
      was only a moderate GFAP positive gliosis. In conclusion, kaolin-induced
      hydrocephalus leads to immune reactions in several defined areas such as
      cholinergic systems, corpus callosum, circumventricular organs, pontine
      cerebellar peduncles and the vestibular nucleus.

PMID- 9522253
TI  - Tri-axial recording of event-related potentials during passive cognitive tasks in
      patients with Alzheimer's disease.
AB  - Standard methods used to assess cognitive function in patients with Alzheimer's
      Disease (AD) often use instructions to direct attention and gauge task
      difficulty, and measure only the output of processing, i.e., the patient's
      behavioral response. Because this may focus assessment on functions that are
      observable and to periods when patient comprehension is not compromised, the
      present study presented stimuli without instruction, manipulated task difficulty
      by varying stimulus factors, and used the brain's electrical response as the
      dependent variable. Because the recording electrode's position on the scalp may
      limit full examination of the voltage distribution of these responses, a Tri
      Axial method of recording electrical activity within a Cartesian coordinate
      system was used. Results suggest attention may inhibit habituation so that inputs
      can be represented, discriminated and consolidated. For the control group, the
      levels of task difficulty modulated electrical peaks presumed to reflect the
      brain's ability to perform these functions. In the AD group, these responses were
      attenuated or absent, suggesting that dysfunctional attentional processing may
      underlie response errors often attributed to memory.

PMID- 9522254
TI  - Scanning eye movements made when viewing film: preliminary observations.
AB  - Eye movements were recorded in 10 adult subjects during the viewing of fiction
      and nonfiction films. Individual differences in scan paths for fiction films were
      found to be relatively small. Generally, eyes concentrated on the screen center
      when looking at characters and objects in rapid motion. Scan paths through the
      screen were observed in special cases, for example, in the case of a dialogue
      between two characters. No differences emerged in scan paths for the same clip
      presented in black-and-white and color versions. Results are relevant for both
      filmmaking and research on perceptual and cognitive strategies involved in
      processing motion pictures.

PMID- 9522255
TI  - Repeated microdialysis from the nucleus tractus solitarii of chronically
      instrumented, unsedated piglets.
AB  - Normal development of respiratory rhythm and control, and perturbations thereof,
      likely relate to neuromodulators in brainstem regions. To assess the feasibility
      of repeated neurochemical sampling by in vivo microdialysis from the respiratory
      related nucleus tractus solitarii (NTS) during development. 19-24 day-old piglets
      (n = 7) were implanted under anesthesia with chronic microdialysis guides near
      NTS around obex. Unsedated piglets then underwent in vivo microdialysis twice, 3
      days apart, through probes inserted acutely via the guides to abut against the
      NTS. The probe tips, surrounded by normal neurons and only diffuse gliosis,
      either intersected, or were within < or = 300 microns from the NTS. Thirty-min
      microdialysates were collected for 120 min in normoxia, HPLC-fractionated, and
      assayed for substance-P (SP), a respiratory excitatory neuropeptide. SP levels
      stabilized within 90 min from probe placement, and did not differ between the 2
      experimental days. Thus, repeated in vivo microdialysis from NTS of conscious
      piglets is feasible, and can illuminate respiratory-related normal and
      pathological neurochemical processes during development.

PMID- 9522256
TI  - Speech impairment in Parkinson's disease is improved by transcranial application
      of electromagnetic fields.
AB  - A 52 year old fully medicated physician with juvenile onset Parkinsonism
      experienced 4 years ago severe "on-off" fluctuations in motor disability and
      debilitating speech impairment with severe stuttering which occurred
      predominantly during "on-off" periods. His speech impairment improved 20%-30%
      when sertraline (75 mg/day), a serotonin reuptake inhibitor, was added to his
      dopaminergic medications which included levodopa, amantadine, selegiline and
      pergolide mesylate. A more dramatic and consistent improvement in his speech
      occurred over the past 4 years during which time the patient received, on a
      fairly regular basis, weekly transcranial treatments with AC pulsed
      electromagnetic fields (EMFs) of picotesla flux density. Recurrence of speech
      impairment was observed on several occasions when regular treatments with EMFs
      were temporarily discontinued. These findings demonstrate that AC pulsed
      applications of picotesla flux density EMFs may offer a nonpharmacologic approach
      to the management of speech disturbances in Parkinsonism. Furthermore, this case
      implicates cerebral serotonergic deficiency in the pathogenesis of Parkinsonian
      speech impairment which affects more than 50% of patients. It is believed that
      pulsed applications of EMFs improved this patient's speech impairment through the
      facilitation of serotonergic transmission which may have occurred in part through
      a synergistic interaction with sertraline.

PMID- 9522257
TI  - Development and course of receptive and expressive vocabulary from infancy to old
      age: administrations of the Peabody Picture Vocabulary Test, Third Edition, and
      the Expressive Vocabulary Test to the same standardization population of 2725
      subjects.

PMID- 9522258
TI  - Neuroprotective effect of chronic verapamil treatment on cognitive and
      noncognitive deficits in an experimental Alzheimer's disease in rats.
AB  - It is well known that disturbance of calcium homeostasis has a significant role
      in the development of neurodegenerative disorders, such as Alzheimer's disease
      (AD). Our recent data suggest that acute treatment with the calcium antagonist
      verapamil can improve some behavioral deficits in an experimental model of AD.
      Therefore, the present study was done to establish the effect of chronically
      administered verapamil on cognitive and noncognitive behavior of rats with
      bilateral electrolitical lesions of nucleus basalis manocellularis (NBM)--an
      animal model of AD. The NBM lesions produce a deficit in performance of diverse
      behavior tests: active avoidance (AA), low level of fear (the open field test) as
      well as aggressive (the test of foot-shock induced aggression) and depressive
      (the learned helplessness test) behavior. Verapamil (1.0, 2.5, 5.0 and 10.0 mg/kg
      i.p.) or saline solution (1 ml/kg i.p.) were injected 24 hr after the lesion of
      NBM and then repeatedly administered during the next 8 days (twice a day).
      Performance of the two-way active avoidance test, the open field test, the foot
      shock-induced aggression test and the learned helplessness test were done on day
      4 after the last verapamil or saline treatment (day 13 after the lesion).
      Verapamil in doses of 2.5 and 5.0 mg/kg significantly ameliorated the deficit in
      the performance of AA, the open field behavior, and the depression, but not the
      aggressive behavior. The obtained beneficial effect of chronic administered
      verapamil suggests that the regulation of calcium homeostasis during the early
      period after NBM lesions might be a reasonable way to prevent the behavioral
      deficits in an experimental model of AD.

PMID- 9522259
TI  - Treatment with electromagnetic fields improves dual-task performance (talking
      while walking) in multiple sclerosis.
AB  - Multiple sclerosis (MS) is associated with an increased risk of falling resulting
      from visual disturbances, difficulties with gait and balance, apraxia of gait and
      peripheral neuropathy. These factors often interact synergistically to compromise
      the patient's gait stability. It has long been recognized that walking involves a
      cognitive component and that simultaneous cognitive and motor operations (dual
      task) such as talking while walking may interfere with normal ambulation. Talking
      while walking reflects an example of a dual-task which is frequently impaired in
      MS patients. Impaired dual-task performance during walking may compromise the
      patient's gait and explain why in some circumstances, MS patients unexpectedly
      lose their balance and fall. Frontal lobe dysfunction, which commonly occurs in
      MS patients, may disrupt dual-task performance and increase the risk of falling
      in these patients. This report concerns a 36 old man with remitting-progressive
      MS with an EDSS score of 5.5 who experienced marked increase in spasticity in the
      legs and trunk and worsening of his gait and balance, occasionally resulting in
      falling, when talking while walking. His gait and balance improved dramatically
      after he received two successive transcranial treatments, each of 45 minutes,
      with AC pulsed electromagnetic fields (EMFs) of 7.5 picotesla flux density.
      Simultaneously, there was improvement in dual-task performance to the extent that
      talking while walking did not adversely affect his ambulation. In addition,
      neuropsychological testing revealed an almost 5-fold increase in word output on
      the Thurstone's Word-Fluency Test, which is sensitive to frontal lobe
      dysfunction. It is suggested that facilitation of dual-task performance during
      ambulation contributes to the overall improvement of gait and balance observed in
      MS patients receiving transcranial treatment with AC pulsed EMFs.

PMID- 9522260
TI  - Assessment of isometric contractions performed with maximal subjective effort:
      corresponding results for EEG changes and force measurements.
AB  - In order to find a parameter or parameters that can be attributed to movements
      performed with maximal subjective effort, EEG recordings and force measurements
      were taken in connection with isometric muscle contractions performed with 80% of
      the subjective maximal force (IMC80) or with maximal subjective effort (IMC100).
      Criteria based on EEG recordings and force measurements have been considered as
      indicators for maximal subjective effort in a given movement. The following
      criteria were selected: A. If the mean spectral theta amplitude across the
      parieto-occipital area decreases from IMC80 to IMC100 then the isometric
      contraction is taken to be performed with maximal effort; B. If the obtained
      force values can be fitted to a switch function and if the achieved forces are
      only a predetermined percentage lower than the maximal force value obtained over
      all trials then this isometric contraction is accepted to be performed with
      maximal effort. 18 out of 24 cases fulfill the EEG criterion whereas the
      criterion for force measurements is fulfilled in 16 out of 24 trials. The
      comparison between the results obtained by means of the EEG criterion and by
      means of criterion for force measurement shows that the results are in agreement
      in 22 out of 24 cases (p < .001). The high correspondence of the assessments
      allows us to suspect that both criteria specify the same phenomenon, namely the
      performance of a motor task with maximal subjective effort.

PMID- 9522261
TI  - P300 and cerebral blood flow before and after TRH in olivopontocerebellar
      atrophy.
AB  - Ten cases of olivopontocerebellar atrophy (OPCA) (mean age 56 +/- 9 years) and 8
      healthy controls (mean age 58 +/- 9 years) were studied. The P300 was measured
      with a Synax 1100 evoked potential recorder and the regional cerebral blood flow
      was measured using the stable xenon computed tomography method. The P300 latency
      was significantly longer in the OPCA group than in the healthy control group. The
      P300 latency after the intravenous infusion of thyrotropin releasing hormone
      (TRH) in the OPCA group was significantly shorter than that before the
      intravenous infusion of TRH. The blood flows in all the measured areas (the
      cerebellar cortex, the cerebellar white matter, the brainstem, the thalamus, the
      basal ganglia, the frontal lobe cortex and the frontal lobe white matter) were
      significantly lower in the OPCA group than in the healthy control group. The
      blood flows in the cerebellar cortex and in the frontal lobe cortex after the
      intravenous infusion of TRH were significantly higher than those before the
      intravenous infusion of TRH. The prolongation of P300 latency in the OPCA group
      suggests that subclinical disturbance in recognition function is present in OPCA
      and may be related to the blood flow decrease outside the cerebellum.

PMID- 9522262
TI  - Local luminance and pattern reversal stimuli yield different visual evoked
      potential topography.
AB  - We studied how the stimulation of quadrants of the visual field affect brain
      potential topography, and we compared activity elicited by conventional pattern
      reversal or by local luminance stimuli. The method of quasi-simultaneous
      stimulation of many small visual field elements by binary m-sequences allowed us
      to reconstruct the potentials evoked at each of 54 visual field locations
      independently. Data from all field elements within each quadrant and in the whole
      stimulation field were summed and compared to those elicited by checkerboard
      reversal stimuli presented in the four quadrants or as full field stimuli. In
      twenty-two healthy adults evoked brain activity was recorded in 30 channels with
      an electrode array densely spaced over the occipital brain areas. With local
      flash stimuli as well as with checkerboard reversal the topographical
      distributions of cortical activation changed significantly with retinal stimulus
      location. Analysis of three components occurring between 50 and 240 ms revealed
      significant differences between pattern reversal and local luminance evoked brain
      activity. Reversal stimuli yielded not only larger amplitudes but also a
      completely different component structure and topography. Our results illustrate
      that different neuronal generators are activated by pattern reversal and local
      luminance stimuli although visual field location of the stimuli was identical
      indicating that the same retinal and cortical structures respond in a different
      way depending on stimulation mode.

PMID- 9522263
TI  - Central motor pathway evaluation using magnetic coil stimulation in hereditary
      motor and sensory neuropathy type I (HMSN type I, Charcot-Marie-Tooth disease).
AB  - Central Motor Conduction Time (CMCT) was investigated in 18 patients (5 m, 13 f;
      age range: 11-69 yrs) with clinical and electrophysiological features of HMSN
      type I, using Magnetic Coil (MC) stimulation. No one exhibited clinically
      pyramidal signs. Brain stimulation Motor Evoked Potentials (MEPs), recorded
      monolaterally from the left abductor digiti minimi (ADM) and tibialis anterior
      (TA) muscles, were evoked in all patients from upper extremities and absent in
      11.1% from lower limbs. Total Motor Conduction Time (TMCT), as well as Peripheral
      Motor Conduction Time estimated by either magnetic nerve root stimulation (mag
      PMCT) or F-wave latency values (F-PMCT), were markedly delayed in all patients.
      Central Motor Conduction Time was calculated by subtracting both the latency of
      mag-PMCT (mag-CMCT) and F-PMCT (F-CMCT) from that one obtained by cortical
      stimulation. F-CMCT was abnormal in 22.2% in upper extremities and in 27.8%
      patients from lower extremities, whereas mag-CMCT in 22.2% from ADM muscles and
      in 33.3% from TA muscles. Furthermore, CMCT to both methods was not possible to
      evaluate in 5.6% from upper and lower extremities and following magnetic root
      stimulation in 11.1% from lower limbs. These findings prove lower motor neuron
      involvement, in agreement with electroneurographic data, and suggest a possible
      central motor pathways impairment, even in patients without any clinical
      evidence, but they cannot explain which is the underlying pathophysiological
      mechanism, a true upper motor neuron involvement or an abnormal spinal motor
      neuron excitability.

PMID- 9522264
TI  - Goal setting as a predictor of return to work in a population of chronic
      musculoskeletal pain patients.
AB  - To assess prospectively the association between personal attributes, vocational
      factors, and the return to work outcome for patients with chronic, nonmalignant,
      musculoskeletal pain, we assessed return to work (RTW) motivation though an open
      format listing of treatment goals in 59 chronic pain patients admitted to a
      university pain management program. Patients were then followed (average of 17.9
      months) in the posttreatment period to determine whether they had in fact
      returned to employment. Results indicated that a number of pretreatment factors
      predicted future employment status in this patient population. Age, marital
      status, education and decreased length of unemployment were predictive of RTW
      outcome. Overall, RTW goal was the single best predictor of return to work
      outcome. In contrast, increased number of premorbid jobs, compensation status,
      patient's race and sex were not predictive. The present study suggests that the
      assessment of an individual's motivation as defined by goal-setting may be a key
      factor in predicting a favorable outcome in this typically refractory population
      of patients.

PMID- 9522265
TI  - Heteronymous monosynaptic Ia facilitation from supine to standing and its
      relationship to the soleus H-reflex.
AB  - To measure changes in presynaptic inhibition, 10 subjects (5 male, 5 female) were
      tested under two conditions: supine and standing. This study utilized the
      heteronymous facilitation protocol, as described by Hulborn et al. (1987a), to
      measure presynaptic inhibition of the Ia afferent pathway onto the soleus alpha
      motoneuron pool. The magnitude of the facilitation produced by the conditioning
      stimulus provides an indirect assessment of presynaptic inhibition from supine to
      standing. Maximal soleus H-reflex (H-max) and motor response (M-max) amplitudes
      were determined prior to testing at each condition. Subjects received 24 test H
      reflex stimuli (approximately 15% M-max), and 24 conditioned stimuli at each body
      position. Results demonstrated a significant decrease in H-max/M-max ratio from
      supine (68.7%) to standing (54.8%). This was the result of changes in H-max
      between the two body positions with no significant changes in M-max. Significant
      inhibition of the conditioned H-reflex was also demonstrated from supine to
      standing (30.7% M-max vs 17.5% M-max). Furthermore, it was demonstrated that a
      strong correlation (r = .85) existed between individual changes in H-max/M-max
      ratio and the changes in facilitation of the conditioned H-reflex from supine to
      standing. This relationship helps explain the modulation of the H-reflex during
      static changes in body position, and it could also provide insight into the
      reflex modulation associated with more functional activities such as walking or
      running. These results are consistent with the hypothesis that presynaptic
      inhibition increases as body position is changed from supine to standing.

PMID- 9522266
TI  - P300 event-related-potential amplitudes and evoked cardiac responses during
      hypnotic alteration of somatosensory perception.
AB  - Ten highly hypnotizable women and 10 women with low hypnotizability were tested
      in a somatosensory target detection task to evaluate the effects of hypnotic
      alterations of somatosensory perception on P3 peak amplitude and evoked cardiac
      response. Stimulus detection task consisted of standard and target electric
      stimuli delivered with a fixed foreperiod. The P3 peak amplitude of ERPs recorded
      from frontal, central and temporo-parieto-occipital (posterior) scalp sites and
      phasic heart rate deceleration response were compared in four conditions: (1)
      normal attention in waking state, (2) hypnotic obstructive hallucination, (3)
      hypnotic attention, (4) hypnotic passive attention. High hypnotizable subjects
      demonstrated significant suppression of P3 peak amplitude to target stimuli in
      the left frontal and posterior scalp sites during hypnotic obstructive
      hallucination as compared to a normal attention condition. In this condition P3
      suppression was paralleled by a smaller anticipatory heart rate deceleration
      response to probe stimulus onset. The P3 peak to standard stimuli was found
      significantly greater in low hypnotizable subjects than for those with high
      hypnotizability regardless of condition. These findings demonstrate that
      hypnotically induced obstructive hallucination to somatosensory stimuli involve
      alterations in neural and autonomic responses and are consistent with a trait
      conception of hypnotizability.

PMID- 9522267
TI  - Science and hyperbole: melatonin.

PMID- 9522268
TI  - Electrophysiological measures of cognition in biological psychiatry: some
      cautionary notes.
AB  - Research into the electrophysiological correlates of mental illness is currently
      expanding, largely because of the availability of relatively inexpensive and
      powerful computers. However, improvements in technology do not always lead to
      enhanced methodological procedures; thus, there are concerns over the proper
      interpretation of the results of these investigations. Our argument is that
      electroencephalographic (EEG) research into psychopathology of psychiatric
      diseases should adopt a cognitivist model of mental dysfunction rather than a
      neurologist model of brain disease. Cognitive science has significant potential
      as an integrative framework for theorizing and researching psychiatric disorders
      and their treatment. Models of human cognitive functioning have rather special
      and unique features; these will make their impact upon the nature of both the
      analysis and interpretation of EEG data. The adoption of a sound model of brain
      function has implications for the methods to be used at different successive
      stages of the research process. We address a number of methodological
      requirements pertaining to: the recording and analysis of EEG signals, the
      laboratory context, the nature of the tasks, and the attribution of obtained
      effects. However, there are grounds for great caution. Even if the mapping of
      electrical changes in brain activity leads to a good approximation of the
      temporal and spatial dynamics of higher brain function, exploitation of such
      information presupposes a deeper understanding of both human cognition and the
      physiological basis of the EEG than is often displayed in the literature. To
      demonstrate this fundamental point, we draw a number of comparisons between
      traditional neurological approaches to brain assessment and contemporary
      cognitive psychophysiology.

PMID- 9522269
TI  - Effects of task variables on the amplitude and phase-locking of auditory gamma
      band responses in human.
AB  - The present study was designed to assess the effects of stimulus certainty and
      motor task-relevance on auditory transient 40-Hz or gamma band responses. To
      study the effects of these factors in a balanced design, auditory event-related
      potentials (ERPs) of 9 young adults were recorded in a passive listening, simple
      reaction task, and choice-reaction task (target tone probability = 0.5)
      conditions. Amplitude and phase-locking of event-related gamma activity were
      analyzed separately at the level of single sweeps by applying a method that
      allows the independent quantification of phase synchronization between
      consecutive single responses. Major results demonstrated that (1) During auditory
      stimulus processing discernible gamma oscillation bursts were observed in three
      time windows of the poststimulus epoch: early (0-120) ms, middle (120-250 ms) and
      late (250-400 ms). (2) Early gamma response amplitudes were significantly largest
      for highly expected motor-task stimuli, whereas the phase-locking did not depend
      on either of the two variables. (3) The phase-locking of late gamma responses,
      however, was significantly stronger to targets than to nontargets. These results
      indicate that auditory gamma responses are functionally involved in the
      processing of task variables such as stimulus certainty and motor-task relevance.
      It is also demonstrated that single gamma response amplitude and phase-locking
      have independent functional significance as being affected in a different manner
      by different task conditions.

PMID- 9522270
TI  - Psychoneuroendocrine immunology: site of recognition, learning and memory in the
      immune system and the brain.
AB  - How the interaction between the brain and immune system takes place has not been
      clearly defined. Because multiple changes are occurring simultaneously in all
      organ systems (e.g., cardiovascular, gastrointestinal, reproductive, renal,
      respiratory, immune, CNS), how many single systems interacts with the brain
      becomes extraordinarily difficult to understand. The problem boils down to
      developing an approach that not only allows one to study the whole organism and
      define the mediators of the interacting systems, but also permit one to establish
      the connection and physiologic relevance of the responses that are being
      evaluated. Conditioning, a phenomenon made popular by the work of Pavlov (1906,
      1927), may provide insight into the pathways of communication between the brain
      and possibly any organ system of the body. Conditioning allows one to separate
      the afferent from the efferent circuits. That is, signals from the immune system
      to the CNS (IS-->CNS) can be effectively separated from signals from the CNS to
      immune system (CNS-->IS). This permits one to study each pathway individually.
      Simple, single association trial models to condition fever, natural killer (NK)
      cell and cytotoxic lymphocyte (CTL) activities have been developed to evaluate
      the pathways. Single trial learning is not new. Pavlov has observed that "The
      electric buzzer set going before administration of food established a conditioned
      alimentary reflex after only a single combination," whereas the reverse order of
      presentation failed to condition the animal (Pavlov 1927 p. 27). Thus,
      conditioning can be used to train the brain to activate the immune system and
      other organ systems participating in the response. During the course of the
      conditioned response, presumably the CNS via the hypothalamus integrates in a
      cohesive orderly fashion all input and output signals and coordinates the
      responses made by the brain to the organ systems. The odor of camphor, the
      conditioned stimulus (CS) can be associated with the response produced by an
      unconditioned stimulus (US). The unconditioned stimuli used are poly I:C to raise
      fever and nonimmunospecific NK cell activity or alloantigens to raise
      immunospecific CTL activity. The unconditioned stimulus serves only as a means to
      activate the immune system and unbalance the homeostasis so that a transient but
      new bidirectional communication loop can be established between the immune system
      and the CNS (IS<-->CNS). The expression of the conditioned response (i.e.,
      elevation of fever, NK cell, or CTL activity) induced with the CS (odor stimulus)
      is an outcome of neural activity (CNS-->IS). This infers that during
      conditioning, the signals generated by the CS and US imprints a neural pathway
      located within the central nervous system and leaves behind a CS/US memory of the
      association. The immune activity (NK cell or CTL activity) which is modulated
      indicate that the memory pathway was activated in the brain of the animal
      expressing the conditioned response. The immune cells that are modulated can be
      considered to be casual bystander cells. These cells however must be in the
      proper (ready) state of activation to receive salient signals from the brain.
      Along with changes in the indicator cell population, other complex physiological
      processes are altered by the brain via sympathetic and neuroendocrine pathways to
      raise the fever response. These observations suggest that the physiological
      changes which are being evaluated such as fever, NK cell or CTL activities or
      perhaps blood pressure, heart rate, fat metabolism, oxygen consumption serve only
      as indicators (readouts), and infer that the CNS has made a coordinated reply in
      response to the CS signal.

PMID- 9522271
TI  - Soluble complement receptor 1 (sCR1) is not as effective as cobra venom factor in
      the treatment of experimental allergic neuritis.
AB  - To further investigate the role of complement activation in Experimental Allergic
      Neuritis (EAN), the effect of systemic complement blockade by soluble CR1 (sCR1)
      was compared to complement depletion by Cobra Venom Factor (CVF) in EAN rats
      immunized with bovine peripheral nerve myelin. EAN rats treated with CVF (n = 10)
      had significantly reduced clinical scores compared to rats treated with sCR1 (n =
      9) or saline (n = 10) (score: sCR1 0.66 +/- 0.7; CVF 0; saline 0.6 +/- 0.8; mean
      +/- SD). CVF treatment more effectively decreased inflammation and demyelination
      compared to sCR1 treatment which had only a partial effect (inflammation: sCR1
      1.8 +/- 1.4; CVF 0.3 +/- 0.7; saline 1.9 +/- 1.2; demyelination; sCR1 1.3 +/- 1;
      CVF 0.1 +/- 0.6; saline 1.7 +/- 1.2). In lumbosacral nerve roots significantly
      less infiltrating ED1 positive macrophages and CD11bc (expressing complement
      receptor 3 or CR3) positive inflammatory cells were present in CVF treated EAN
      rats while there was a limited decrease in inflammation in the sCR1 treated
      animals compared to the saline treated rats (ED1: sCR1 1.4 +/- 1.2; CVF 0.5 +/-
      0.6; saline 1.7 +/- 1.2; CD11bc: sCR1 1.9 +/- 1.2; CVF 0.9 +/- 1; saline 2.1 +/-
      1.2). Our findings suggest that complement depletion by CVF is more effective
      than complement blockade by sCR1 in reducing the severity of inflammatory
      peripheral nerve demyelination.

PMID- 9522272
TI  - Differentially expressed genes associated with 5-Aza-2'-deoxycytidine-induced
      hindlimb defects in the Swiss Webster mouse.
AB  - 5-Aza-2'-deoxycytidine (d-AZA) inhibits methylation of DNA, a process that serves
      as an epigenetic regulator of gene expression. We have shown that d-AZA causes
      temporally related defects in mice. Gestational day (GD) 10 treatment induced
      severe long-bone defects of the hindlimb but not the forelimb. Exposure of
      younger embryos (GD 8 or 9) does not induce similar defects in forelimbs. This
      limb-dependent response suggests that methylation alterations in genes specific
      for fore- or hindlimbs may contribute to the observed pattern of defects.
      Subtraction hybridization (SH) studies were conducted to identify differential
      expression of DNA subsequent to the administration of d-AZA to mice on GD 10.
      Hindlimb buds collected from both treated and untreated embryos at 4, 12, and 24
      hours post-treatment were used. A clone isolated from the untreated sample (down
      regulation in treated tissue) was identified as a member of the murine B1 family
      of repetitive sequences. The two other clones isolated from the treated tissue
      (up-regulation) were homologous to avian myogenic regulatory protein mRNA and
      activin receptor type II gene. Both species are active during embryogenesis.
      These findings suggest that the isolated clones may have roles in abnormal
      embryonic development when inappropriately expressed.

PMID- 9522273
TI  - Streptozotocin may provide protection against subsequent oxidative stress of
      endotoxin or streptozotocin in rats.
AB  - Endotoxin lipopolysaccharide (LPS) and streptozotocin-induced diabetes are known
      to cause oxidative stress in vivo. There is some evidence that a sublethal dose
      of LPS provides protection against subsequent oxidative stress. Because of its
      wide use as a diabetogenic agent, this study was undertaken to determine if
      streptozotocin can likewise provide a protective effect against further oxidative
      stress in rats. Female Sprague-Dawley rats were given streptozotocin (50 mg/kg
      intraperitoneally once) prior to exposure to either bacterial endotoxin from
      Salmonella abortus equii (5 mg/kg intraperitoneally) or three additional daily
      doses of streptozotocin (50 mg/kg intraperitoneally). One week after LPS or
      streptozotocin treatments, oxidative stress was determined by measuring changes
      in antioxidant activity (glutathione peroxidase, glutathione reductase,
      superoxide dismutase, catalase, glutathione S-transferase, and gamma
      glutamyltranspeptidase) and in concentrations of glutathione, nitrite, and
      thiobarbituric acid reactants in liver, kidney, intestine, and spleen. High
      levels of some antioxidants in the LPS-control and streptozotocin-control rats,
      in contrast to normal levels found in diabetes + LPS and multidose-streptozotocin
      rats, suggest that streptozotocin, like LPS, may confer a protective effect
      against subsequent oxidative stress.

PMID- 9522274
TI  - Development of a radiolabeled ATP assay for carboxylic acid:CoA ligases and its
      use in the characterization of the xenobiotic carboxylic acid:CoA ligases of
      bovine liver mitochondria.
AB  - A radiolabeled ATP assay was developed for measuring carboxylic acid:CoA ligase
      activity. The assay was designed to measure the formation of [gamma
      33P]pyrophosphate from [gamma-33P]ATP in the course of the reaction. The assay
      was linear with protein concentration, and rates as low as 1 pmol/min were
      measurable. Rates determined with this assay were in agreement with rates
      determined with [14C]carboxylic acids. The assay was used to characterize the
      substrate specificity of the XL-I, XL-II, and XL-III ligases from bovine liver
      mitochondria. Forty carboxylic acids were tested for activity. The enzymes
      differed in their substrate specificities with XL-I and XL-II being the most
      similar and XL-III having the broadest specificity. This study has uncovered 19
      new carboxylic acids that are substrates for these enzymes.

PMID- 9522275
TI  - Involvement of cytochrome P450 3A in the metabolism and covalent binding of 14C
      monocrotaline in rat liver microsomes.
AB  - The metabolism and covalent binding of 14C-monocrotaline in Sprague-Dawley (SD)
      rat liver microsomes was investigated using the inducers dexamethasone,
      clotrimazole, pregnenolone-16 alpha-carbonitrile, and phenobarbital.
      Monocrotaline is a pyrrolizidine alkaloid (PA) that causes a syndrome in rats
      that is a model for human primary pulmonary hypertension. It has been documented
      that bioactivation of PAs (dehydrogenation to reactive pyrroles) in the liver by
      cytochromes P450 is required for their toxicity. Covalent binding of these
      reactive pyrroles to tissue macromolecules has been hypothesized to correspond to
      PA toxicosis. We correlated metabolism and total microsomal covalent binding of
      14C-monocrotaline with cytochrome P450 3A using the aforementioned inducers,
      troleandomycin (a cytochrome P450 3A inhibitor), erythromycin N-demethylase assay
      of cytochrome P450 3A activity, and Western blots employing anti-rat cytochrome
      P450 3A antibodies. In addition, autoradiography of membranes electroblotted from
      SDS-PAGE demonstrated the formation of radiolabeled adducts with specific
      protein(s). The most intensely radiolabeled protein bands have an apparent
      molecular weight of approximately 52 kDa, which was similar to the molecular
      weight detected by anti-rat cytochrome P450 3A antibodies in the Western blots.
      No radiolabeled proteins were detected in microsomes pretreated with
      troleandomycin.

PMID- 9522276
TI  - Thymidylate synthase activity and the cell growth are inhibited by the beta
      carboline-benzoquinolizidine alkaloid deoxytubulosine.
AB  - Employing thymidylate synthase (TS) (5, 10-CH2-H4PteGlu: dUMP C
      methyltransferase, EC 2.1.1.45), a key target enzyme in chemotherapy, the
      biological activity of the beta-carboline-benzoquinolizidine alkaloid
      deoxytubulosine (DTB) isolated from the Indian medicinal plant Alangium lamarckii
      has been evaluated and assessed for the first time. The TS employed in the
      present studies was purified from Lactobacillus leichmannii. The DTB was
      demonstrated to exhibit potent cytotoxicity and inhibited the cell growth of L.
      leichmannii, and DTB potently inhibited TS activity (IC50 = 40 microM). The DTB
      concentrations > 80 microM resulted in a total loss of the TS activity, thus
      suggesting that the beta-carboline-benzoquinolizidine alkaloid is a promising
      potential antitumor agent. The DTB binding to TS appears to be irreversible and
      tight through a possible covalent linkage. Although DTB strongly binds to DNA, it
      is not known whether DTB binds to RNA associated with TS. Inhibition kinetics
      showed that TS has a Ki value of 7 x 10(-6) M for DTB and that the inhibition is
      a simple linear "noncompetitive" type.

PMID- 9522277
TI  - N-dealkylation of aminopyrine catalyzed by soybean lipoxygenase in the presence
      of hydrogen peroxide.
AB  - A hypothesis that lipoxygenase may mediate N-dealkylation of xenobiotics was
      investigated using the prototype drug aminopyrine and soybean lipoxygenase as a
      model enzyme in the presence of hydrogen peroxide. Formaldehyde production as a
      result of N-demethylation of aminopyrine exhibited pH optimum of 6.5. The
      reaction was dependent on the incubation time, amount of enzyme, and
      concentration of aminopyrine and hydrogen peroxide. Under the experimental
      conditions employed, the specific activity for N-demethylation of aminopyrine was
      found to be 823 +/- 93 nmoles per min/mg protein or 89 +/- 10 nmoles per
      min/nmole of enzyme. The reaction was significantly inhibited by
      nordihydroguaiaretic acid and gossypol, the classical inhibitors of lipoxygenase.
      Spectrophotometric analyses indicated the generation of a nitrogen-centered free
      radical cation as the initial oxidation product of aminopyrine. The rate of
      accumulation of this radical species was also dependent on pH, the amount of
      enzyme, and concentration of aminopyrine and hydrogen peroxide. The radical
      production was markedly suppressed by ascorbate, glutathione, and dithiothreitol
      in a concentration-dependent manner. Preliminary data gathered for the oxidation
      of other chemicals indicated that the lipoxygenase exhibits a unique substrate
      specificity. Collectively, the evidence presented suggests for the first time
      that lipoxygenase pathway may be involved in N-demethylation of aminopyrine and
      other chemicals.

PMID- 9522278
TI  - Protein oxidation: examination of potential lipid-independent mechanisms for
      protein carbonyl formation.
AB  - Previous data indicated that diquat-mediated protein oxidation (protein carbonyl
      formation) occurs through multiple pathways, one of which is lipid dependent, and
      the other, lipid independent. Studies reported here investigated potential
      mechanisms of the lipid-independent pathway in greater detail, using bovine serum
      albumin as the target protein. One hypothesized mechanism of protein carbonyl
      formation involved diquat-dependent production of H2O2, which would then react
      with site-specifically bound ferrous iron as proposed by Stadtman and colleagues.
      This hypothesis was supported by the inhibitory effect of catalase on diquat
      mediated protein carbonyl formation. However, exogenous H2O2 alone did not induce
      protein carbonyl formation. Hydroxyl radical-generating reactions may result from
      the H2O2-catalyzed oxidation of ferrous iron, which normally is bound to protein
      in the ferric state. Therefore, the possible reduction of site-specifically bound
      Fe3+ to Fe2+ by the diquat cation radical (which could then react with H2O2) was
      also investigated. The combination of H2O2 and an iron reductant, ascorbate,
      however, also failed to induce significant protein carbonyl formation. In a
      phospholipid-containing system, an ADP:Fe2+ complex induced both lipid
      peroxidation and protein carbonyl formation; both indices were largely
      inhibitable by antioxidants. There was no substantial ADP:Fe(2+)-dependent
      protein carbonyl formation in the absence of phospholipid under otherwise
      identical conditions. Based on the lipid requirement and antioxidant sensitivity,
      these data suggest that ADP:Fe(2+)-dependent protein carbonyl formation occurs
      through reaction of BSA with aldehydic lipid peroxidation products. The precise
      mechanism of diquat-mediated protein carbonyl formation remains unclear, but it
      appears not to be a function of H2O2 generation or diquat cation radical
      dependent reduction of bound Fe3+.

PMID- 9522279
TI  - Seeing difference: market health reform in Europe.
AB  - The comparative literature on health care reform has identified a convergence
      upon market models as nations respond to similar economic, technological, social,
      and demographic pressures. In this article I first challenge the conventional
      view by comparing "market" reforms of the late 1980s and early 1990s in the
      United Kingdom, the Netherlands, and Sweden. Though these nations did indeed
      converge upon the instrument of the market incentive, there was considerable
      divergence in the content and aims of their reform strategies. These nations
      designed their respective markets to make different tradeoffs among competing
      values. While all three exploited the principle of provider competition, they
      appointed different actors to judge the contest: the cost-conscious public
      authority in the United Kingdom, the quality-conscious patient in Sweden, and the
      optimizing consumer in the Netherlands. I argue that these countries were thus
      using common market tools to promote different health policy goals.
      Distinguishing these reforms further is the fact that--particularly in the
      Netherlands--there was a gap between market plans and the reality of implemented
      change. I then ask why nations responded so differently to such similar objective
      pressures. My contention is that this divergence reflects, in part, the different
      ideological orientations of the ruling party or coalition in each nation. Yet
      divergence is also the result of differences in both the design of political
      institutions and the structure of the pre-reform health system in each country.

PMID- 9522280
TI  - Exceptionalism as the rule? U.S. health policy innovation and cross-national
      learning.
AB  - American health care reformers, who often look to other nations for models of
      desirable health systems, are often surprised nowadays by cross-national
      infatuation with health policy innovations minted in the United States. American
      innovations appeal to policy makers abroad as they struggle with cost pressures,
      distinguish knowledge about how health systems work, and deal with changing
      images of what constitutes good public policy. These strategems are adapted, not
      adopted; however, the premises and practices with which other nations follow
      American directions differ deeply from those in the United States. Ironically,
      even cross-national experiments may end up offering instructive policy "rules" to
      the exceptionalist United States.

PMID- 9522281
TI  - Do uncompensated care pools change the distribution of hospital care to the
      uninsured?
AB  - In 1983, New York State established an uncompensated care pool using the New York
      Prospective Hospital Reimbursement Methodology (NYPHRM). Two policy objectives of
      the NYPHRM were (1) to encourage more equitable distribution of uncompensated
      care across hospitals and (2) to increase access to hospital care for the
      uninsured. This article demonstrates that the New York uncompensated care pool
      was only moderately successful in achieving these goals. The principal findings
      are that the NYPHRM did result in routine care being redistributed away from
      hospitals that traditionally provided care to the uninsured, while provision of
      highly technological care was not significantly redistributed. This article
      suggests that if the primary policy goal is to increase access to care for the
      uninsured by changing the distribution of hospitals willing to provide care, the
      uncompensated care pool approach is moderately effective.

PMID- 9522282
TI  - Addressing racial inequities in health care: civil rights monitoring and report
      cards.
AB  - Large racial inequities in health care use continue to be reported, raising
      concerns about discrimination. Historically, the health system, with its
      professionally dominated, autonomous, voluntary organizational structure, has
      presented special challenges to civil rights efforts. De jure racial segregation
      in the United States gave way to a period of aggressive litigation and
      enforcement from 1954 until 1968 and then to the current period of relative
      inactivity. A combination of factors--declining federal resources and
      organizational capacity to address more subtle forms of discriminatory practices
      in health care settings, increasingly restrictive interpretations by the courts,
      and the lack of any systematic mechanisms for the statistical monitoring of
      providers--offers little assurance that discrimination does not continue to play
      a role in accounting for discrepancies in use. The current rapid transformation
      of health care into integrated delivery systems driven by risk-based financing
      presents both new opportunities and new threats. Adequate regulation, markets,
      and management for such systems impose new requirements for comparative
      systematic statistical assessment of performance. My conclusion illustrates ways
      that current "report card" approaches to monitoring performance of such systems
      could be used to monitor, correct, and build trust in equitable treatment.

PMID- 9522283
TI  - Senate voting and social construction of target populations: a study of AIDS
      policy making, 1987-1992.
AB  - Scholars have devoted considerable attention to analyzing the social construction
      of AIDS. To explore the politics of AIDS policymaking, this research uses
      Schneider and Ingram's (1993) theory of the social construction of target
      populations to evaluate the U.S. Senate's response to AIDS between 1987 and 1992.
      Our study found that Schneider and Ingram's model provides important insights
      into how political processes affect AIDS policy design. While our data did not
      strictly conform to all of the model's theoretical expectations, the data
      provided evidence confirming its predictions about broad patterns in the
      allocation of both substantive and symbolic policy benefits and burdens to
      different target populations.

PMID- 9522284
TI  - Interactions between mental health and law enforcement systems: problems and
      prospects for cooperation.
AB  - This article examines the challenges posed by system specialization, as
      illustrated by the difficulties of coordinating the roles of the mental health
      and law enforcement agencies working with people with severe mental illness.
      Dealing with the needs of clients in one system when they are most appropriately
      served by the other may make both law enforcement and mental health systems
      appear ineffective and inefficient. This could increase the incidence of
      disorderly or violent behavior, which forments the myth that the seriously
      mentally ill are inherently dangerous. Despite the evident need to manage these
      issues, conventional methods of coordinating services have failed. This article
      concludes by developing a contracting model that creates more appropriate
      incentives for the two systems and bridges the gap between them.

PMID- 9522285
TI  - The economic impact of biomedical research: a case study of voluntary
      institutions in the New York metropolitan region.
AB  - This study estimates the economic significance of biomedical research for a
      geographic region. Through a survey of nonprofit biomedical research institutions
      in the metropolitan New York region and an analysis of research budget data
      obtained from the area's six largest research institutions, estimates were made
      of the spending effect of biomedical research on the region. Biomedical research
      undertaken by the voluntary institutions in metropolitan New York accounted for
      almost $1.15 billion per year in direct spending in 1991. When the indirect and
      induced ripple effects of this spending on the regional economy were considered,
      the total annual spending impact was over $2.3 billion. Sponsored biomedical
      research directly generated 19,816 jobs per year in the host institutions. The
      indirect and induced job creation in the region amounted to an additional 12,773
      jobs per year for a total of almost 32,600 regional jobs per year. As economic
      development becomes more competitive locally, regionally, and internationally,
      the biomedical sciences that have always been intrinsically valued gain extrinsic
      value. Therefore, techniques for estimating their economic impact are becoming
      increasingly important.

PMID- 9522286
TI  - Investigation of infection in the neutropenic patient with fever.
AB  - Episodes of infection occurring in neutropenic patients are often associated with
      high levels of morbidity and mortality and prompt, accurate diagnosis allowing
      the rapid instigation of appropriate treatment can lead to an improved outcome.
      Recent developments in laboratory technology have increased the range of
      investigations available to the physician. The improved sensitivity of
      traditional microbiological culture, methods for antigen and antibody detection
      and the advances in molecular biology are among the reasons for an increased
      ability to detect both familiar and novel pathogens. This article describes the
      current methods available for determining the aetiology of an infectious episode
      in these patients. A plan of management for investigation of febrile episodes in
      neutropenic patients is suggested.

PMID- 9522287
TI  - Recurrence of symptoms in Clostridium difficile infection--relapse or
      reinfection?
AB  - We have fingerprinted Clostridium difficile isolates from patients with
      symptomatic recurrences of infection, using random amplified polymorphic DNA
      (RAPD). The medical records of 55/79 patients were examined, from whom multiple
      C. difficile-positive faeces were received during hospitalization at least five
      days, but no more than two months, apart. In 20 of these cases symptoms either
      did not recur (i.e., absent for at least three days between episodes), or were
      explainable by other causes, such as laxative administration. Of the remaining 35
      patients, 27 sets of C. difficile isolates (23 pairs and four triplicates) were
      available for RAPD fingerprinting. Differing C. difficile DNA fingerprints (at
      least three major bands difference) were obtained for 15/27 patients, and hence
      at least 56% of the clinical recurrences of infection were in fact due to re
      infection as opposed to relapse. Since we found that an endemic C. difficile
      clone was present in 18 out of 27 patients (67%) and accounted for 53% (31/58) of
      all isolates, it is probable that the majority of symptomatic recurrences are in
      fact re-infections, with either a different or the same C. difficile strain. We
      conclude that more attention must be given to preventing the re-infection of C.
      difficile symptomatic patients. Isolation of symptomatic individuals is the
      preferred option for the protection of other patients, but measures must be taken
      to ensure that further strain acquisition by the index cases does not occur.

PMID- 9522288
TI  - Simultaneous outbreaks of two strains of toxigenic Clostridium difficile in a
      general hospital.
AB  - We report an outbreak of Clostridium difficile-associated disease (CDAD) in a
      large Dublin hospital. From January to June 1995, inclusive, 139 patients were
      affected; the mean age of cases was 68.8 +/- 19 years. Clinical information is
      available for 73 cases identified during the first four months of the outbreak.
      The majority of patients presented with abrupt onset of watery diarrhoea;
      however, 19.2% presented with an unexplained pyrexia following a course of
      antimicrobial therapy and 5.5% presented with a surgical acute abdomen. Twenty
      patients (27.4%) experienced relapsing disease and seven (9.6%) patients died.
      Seventy-six percent of cases received a cephalosporin prior to the onset of
      disease, the highest relative risks occurring with third-generation agents;
      however, 9.6% of patients affected had not been exposed to antimicrobial therapy
      in the preceding eight weeks. Pyrolysis mass spectrometry identified two clusters
      of isolates, representing two strains of C. difficile. There was marked spatial
      clustering of these strains, with each confined to a separate area of the
      hospital. Infection control measures and an antibiotic policy were introduced.
      Throughout the outbreak period the use of the most frequently used cephalosporin
      in the hospital increased; this was accompanied paradoxically by a reduction in
      the number of new cases of CDAD.

PMID- 9522289
TI  - Rhizopus microsporus in wooden tongue depressors: a major threat or minor
      inconvenience?
AB  - The investigation and management of an apparent outbreak of Rhizopus spp. in a
      London paediatric referral centre between September 1995 and April 1996 is
      described. The organism was identified in microbiological surveillance samples
      from 23 patients nursed in four hospital areas. Investigations revealed the
      presence of the organism in spatulae from all ward areas investigated and from
      closed boxed containers held in the central hospital stores obtained from a new
      supplier. In contrast, culture of spatulae from the initial supplier failed to
      yield any fungal isolates. The incident was reported to the Medical Device Agency
      (MDA), the Central Public Health Laboratory Service (CPHLS) and the Birmingham
      PHLS. A statement was prepared for the weekly Communicable Disease Report and a
      hazard warning issued by the MDA. The spatulae were withdrawn from use and the
      contract with the original supplier was re-established. This incident resulted in
      contamination of samples only and no patient involvement. It highlights the
      problems which may follow use of equipment for unintended purposes and the need
      for good manufacturing practice guidelines to be applied to non-sterile equipment
      used in direct patient care.

PMID- 9522290
TI  - Epidemiology of Klebsiella bacteraemia: a case control study using Escherichia
      coli bacteraemia as control.
AB  - Epidemiological data from 117 episodes of Klebsiella bacteraemia were compared
      with those from matched controls with Escherichia coli bacteraemia. Cases and
      controls were obtained from 20,631 blood cultures taken from patients in Hvidovre
      Hospital between 1990 and 1992. The data studied included: sex and age, risk
      factors, portal of entry, outcome, nosocomial acquisition and distribution within
      the hospital. The incidence of Klebsiella bacteraemia was 9.3/10,000 admissions
      (76% Klebsiella pneumoniae; 24% Klebsiella oxytoca). Patients with Klebsiella and
      E. coli bacteraemia had many common features, including a high incidence of
      neoplastic disease, biliary tract disease, and renal failure. Many had undergone
      surgery or received therapy with steroids, antacids or antibiotics. Klebsiella
      bacteraemia was more often found in males, in patients with hospital contact
      within the previous month, and polymicrobial infection. Logistic regression
      analysis showed that use of invasive plastic devices and diabetes were
      significantly associated with Klebsiella bacteraemia. The urinary tract was the
      commonest source, followed by the biliary tract; 27% of patients had no obvious
      focus of infection, and in many of these an invasive device may have been
      involved. Forty-five K-serotypes were found--the largest number being nine
      strains of type K3; only a few strains had acquired resistance characters to
      antimicrobial agents. There were no differences between community- and hospital
      acquired strains; indicating that our hospital does not have a resident strain of
      Klebsiella.

PMID- 9522292
TI  - Growth and enterotoxin production by diarrhoeagenic Bacillus cereus in dietary
      supplements prepared for hospitalized HIV patients.
AB  - This study was initiated because of an increase in diarrhoeal episodes in a ward
      caring for patients infected with the human immunodeficiency virus (HIV). An
      examination of hospital-prepared dietary supplements (build-up food) found
      Bacillus cereus to be a potential problem. Due in part to inadequate
      refrigeration conditions (13 +/- 4 degrees C), the microbial flora in
      commercially pasteurized semi-skimmed milk (PSSM) reached potentially hazardous
      levels (> 10(6) cfu/mL). While refrigerated PSSM did not support enterotoxin
      production, reconstitution of build-up powder in PSSM followed by storage in the
      HIV ward (4 h at 28 +/- 3 degrees C) resulted in growth of B. cereus (> 10(7)
      cfu/mL) and synthesis of diarrhoeal enterotoxin. While insufficient
      epidemiological data was available to establish conclusively a causal
      relationship between patients' symptoms and source, the study highlights a
      potential B. cereus problem with hospital-prepared dietary supplements and
      recommendations are proposed to prevent this re-occurrence.

PMID- 9522291
TI  - Frequency of parenteral exposure and seroprevalence of HBV, HCV, and HIV among
      operation room personnel.
AB  - A study was designed to determine the frequency of needle-stick injuries,
      immunization status for hepatitis B virus (HBV) and sero-prevalence of HBV,
      hepatitis C virus (HCV), and human immunodeficiency virus (HIV) infections among
      operation room personnel. Self-assessment questionnaires were completed and blood
      tested for HBsAg, anti-HBc (total), anti-HCV and anti-HIV. Of 114 operation room
      personnel studied, the majority (58.8%) reported more than four needle-stick
      injuries per year, 36.8% one to three needle-stick injuries per year, while 4.4%
      reported no needle-stick injury in the last five years. Thirty-six percent of
      personnel had received a complete course of hepatitis B vaccination. There was
      serological evidence of hepatitis HBV virus and/or HCV infections in 31% of the
      studied population. Four percent were reactive for HCV infection, 7.5% for HBsAg
      infection and 25.43% for anti-HBc (total); none was HIV positive. Eighty percent
      of the HCV positive and 55% of the anti-HBc (total) positive personnel had more
      than four needle-stick injuries per year in the last five years, while 75% HBsAg
      reactive personnel had received one to three needle-stick injuries per year. This
      study indicates a need for continued efforts to minimize the risk of blood-borne
      infection by enhancing the compliance of operation room personnel with HBV
      vaccination and adherence to infection control measures.

PMID- 9522293
TI  - Nosocomial outbreak of multi-resistant Acinetobacter sp. on an intensive care
      unit: possible association with ventilation equipment.

PMID- 9522294
TI  - Antibiotic resistant Escherichia coli in a Sudanese hospital.

PMID- 9522295
TI  - Risk factors and outcome of non-Candida spp. yeasts causing fungaemia in cancer
      patients: comparison with Candida albicans.

PMID- 9522296
TI  - Bacteraemia complicating coronary artery stenting.

PMID- 9522297
TI  - [Organization of the Pediatric Tumor Cell Bank of the Society of Pediatric
      Oncology and Hematology (GPOH)].
AB  - Characterized cell lines are absolutely necessary in applied research of cell
      biology and medicine. For the completion of diagnosis and therapy especially in
      pediatric oncology we are establishing a Cell Bank for Pediatric Tumors. The Cell
      Bank for Pediatric Tumors collects tissue samples of different types of solid
      malignant tumors from children and young adults. The specimens are transferred to
      in vitro culture (guidelines of the American Type Culture Collection-ATCC), the
      resulting cells are characterized to assure accordance with the histogenesis of
      the original tumor and stored in liquid nitrogen. The cell cultures are
      characterized morphologically (phase contrast microscopy) and
      immunocytochemically (ABC-method). To prove the malignancy of cells in primary
      culture the amount of hypertetraploid cells was determined (DNA-Scanning
      Cytophotometry). Cell lines are checked to find out whether they develop tumors
      in nude mice followed by an analysis of the karyotype. Additional investigations
      (e.g. in vitro test of cytostatic drug resistance) are carried out on request by
      the sender. Part of the tumor tissue which is used to start the cell culture is
      in parallel diagnosed histopathologically at the Children's Tumor Register, Kiel
      and/or at the Charite. By the end of the year 1995 the Cell Bank for Pediatric
      Tumors had received 183 different specimens including 123 solid tumors (e.g. 24
      neuroblastomas, 18 osteosarcomas, 12 Wilms' tumors, 13 rhabdomyosarcomas), 44
      tissue specimens without any malignant cells, 8 probes without vital cells and 8
      leukemias and lymphomas. We were able to establish primary cell cultures of 50%
      of the sterile tumor tissue probes, to cultivate them for a minimum of 5-10
      passages, to characterize and freeze them. Six out of these tumor cell lines were
      already cultivated for one year and are available to the scientific community.

PMID- 9522298
TI  - [Manifestations of sickle cell disease in adolescents and young adults. Clinical
      aspects and therapy references].
AB  - In Germany about 300 sickle cell patients are being seen at more than 100
      different hospitals. One third of these patients are adolescents and young
      adults. Since this is a congenital chronic disease, the majority of these
      teenagers and young adults are being cared for by pediatricians. Sickle cell
      disease in patients older than 15 years is characterized by the development of
      chronic organ damage, in addition to the occurrence of acute manifestations of
      disease such as pain crises, splenic sequestration, aplastic crises and Acute
      Chest Syndrome. Pediatricians who care for older sickle cell patients have to
      handle not only internal medicine problems but also to answer questions
      concerning pregnancy and contraception. In this paper the specific problems of
      adolescents and young adults with sickle cell disease are presented and
      suggestions are offered for the care of this group of patients.

PMID- 9522299
TI  - [Value of the new anticonvulsants in pediatrics].
AB  - Within the last years five new antiepileptics have become available in Germany.
      Vigabatrin is a second choice drug against partial seizures, West syndrome and
      epilepsies in infant encephalopathy syndromes. Lamotrigine and Gabapentin can be
      used as add-on therapy in partial seizures in children above 12 years of age
      Felbamate has a high incidence of severe side-effects like aplastic anemia and
      liver failure. Therefore it should be restricted to the treatment of Lennox
      Gastaut syndrome. Oxcarbazepine is not yet on the German market, but is available
      by import from Austria. Its therapeutic range is similar to carbamazepine with
      less side-effects. The new antiepileptics discussed have turned out to be useful
      additional therapeutics, especially in focal epilepsies. There is, however, still
      limited experience with these drugs in children. So none can as yet be considered
      a drug of first choice in any epileptic childhood disorder. The classical
      antiepileptic drugs remain essential in antiepileptic therapy.

PMID- 9522300
TI  - [Predictors of follow-up course of asthma complaints in early childhood--results
      of a follow-up study].
AB  - A follow-up study was undertaken to determine the predictors of the course of
      recurrent wheezing episodes in children (between 0 to 8 years). In 1991, 600
      children with wheezing episodes had been recorded by physicians who participated
      in a sentinel practice network. On each consultation with the same physicians
      from October 1994 until June 1995, parents of these children were questioned
      again about the course of their respiratory symptoms (n = 218). Associations
      between the course of disease and predictors (recorded by physicians in 1991)
      were analysed using polytomous logistic regression. The following factors were
      significantly associated with the frequency of asthmatic episodes (odds ratio
      (OR) > 1 indicates an unfavourable course of disease in comparison with the
      reference category, [95% confidence interval]): indoor cigarette smoking: OR =
      1.7; [1.0-3.0], older than 1 year of age (reference: < 1 year): OR = 3.0; [1.1
      8.5], more than 5 asthmatic episodes during the year before the first
      registration: OR = 2.7; [1.3-5.6], infect-associated asthma: OR = 0.4 [0.2-1.0],
      paediatrician as recording physician (reference: general practitioner): OR = 0.4
      (0.2-0.8). No significant association with the course of disease was found for
      sex, education of the parents, region, parental asthma, hospital admissions
      because of obstructive symptoms. In correspondence with other studies, the
      majority of children showed a favourable course of their obstructive respiratory
      symptoms: for only 7% the frequency of episodes increased during 3 years after
      the first contact. Indoor smoking and severity of asthma are known as predictors
      of the course of the disease. The better prognosis of infect-associated
      obstructive symptoms supports the thesis that the majority of infants with
      asthmatic symptoms have narrow, infect-mediated airways obstructions, but no
      increased risk for bronchial asthma in their later lives. An early identification
      of children at risk may allow a specific and intensified therapy to improve the
      course of disease.

PMID- 9522302
TI  - [Monitoring kidney function during neonatal intensive care: comparison between
      Doppler ultrasound findings and renal function parameters].
AB  - 33 neonates between 4th and 7th day of life were enrolled in the study. The data
      of renal Doppler sonography were compared to renal excretion parameters. In
      infants with respiratory distress a decrease of creatinine clearance as well as
      an increase of fractional sodium excretion were associated with reduced peak
      systolic flow velocity in the A. renalis. The results suggest the importance of
      the Doppler sonography in the monitoring of the renal function in the newborn
      intensive care.

PMID- 9522301
TI  - [Symptomatic congenital complete atrioventricular block--a medical challenge].
AB  - Congenital complete atrioventricular block is a rare entity. The association
      between this disease, maternal connective tissue disease and maternal antibodies
      [anti-Ro (SS-A) resp. anti-La (SS B)] is well known. Diagnosis can be made by
      means of fetal Doppler-echocardiography by the 16th week of gestation. In our
      case diagnosis was established in the 21st week of gestation. Ventricular rate
      was 55/min, atrial rate 70/min. There were no signs of fetal hydrops. There were
      no signs of maternal connective tissue disease, but anti-Ro and anti-La
      antibodies could be detected. The mother was treated with steroids from the time
      of diagnosis until the end of pregnancy. Altogether 9 Doppler-echocardiographic
      studies were performed. A recurrence of normal rhythm did not occur. A slow but
      continuous decrease of atrial and ventricular rate was observed. Interestingly,
      there was no development of fetal hydrops until the very end of pregnancy when
      the fetal heart rate reached a low of 28 beats per minute. We speculate, that the
      therapy with steroids might have played an important role in the prevention of
      early hydrops. At the onset of fetal hydrops delivery should be considered. In
      symptomatic complete atrioventricular block we prefer the implantation of a
      permanent pacemaker system immediately after birth. Efficient care for the fetus
      resp. the newborn can only be achieved through well planned cooperation.

PMID- 9522303
TI  - [Functional disorder of the hypothalamic osmoreceptor as the cause of excessive
      hypernatremia in a girl with absence epilepsy].
AB  - BACKGROUND: Chronic hypernatremia is a rare disorder in childhood and normally
      results from impairment of the water homeostasis. In some cases, chronic
      hypernatremia is caused by decreased intake of water based on impaired thirst
      perception. CASE REPORT: We report a girl with microcephaly, partial agenesis of
      the corpus callosum, mild midface hypoplasia and absence seizures, who presented
      with severe hypernatremia (serum sodium concentration 189 mmol/l). Though serum
      osmolality was increased up to 382 mOsm/kg, the girl showed no signs of thirst.
      After normalization by intravenous fluid therapy, serum osmolality and serum
      sodium concentration remained in the normal range with an oral water intake of at
      least 1500 ml/d. Polyuria was never present, the ability to concentrate urine was
      preserved. CONCLUSIONS: In summary, we speculate that the chronic hypernatremia
      in our patient is caused by a selective hypothalamic osmoreceptor dysfunction
      associated with mild dysplasia of the midline structures. Only very few similar
      cases have been documented in the literature.

PMID- 9522304
TI  - [Eruptive melanocytic nevi after chemotherapy].
AB  - BACKGROUND: Induction of melanocytic naevi by chemotherapy in children is
      reported in the literature. The reason for this phenomenon is not known yet.
      HISTORY AND CLINICAL FINDINGS: We present a 6-year-old girl who fell ill with
      acute lymphoblastic leukemia at the age of 2 years. After a combined
      chemotherapeutic treatment for 2 years followed by complete remission of
      leukemia, many (> 100) small pigmented naevi appeared over the whole body. The
      naevi did not show features suggestive of dysplasia. CONCLUSIONS: Patients with
      excess numbers of melanocytic naevi constitute a risk group for malignant
      melanoma, therefore periodic skin examination is recommended.

PMID- 9522305
TI  - [Peliosis hepatis with hepato-pulmonary syndrome].
AB  - Sinusoidal dilatation is a hallmark of peliosis hepatis, a rare vascular disorder
      that can be either drug induced or of infectious origin. Here we report a patient
      with peliosis hepatis of unknown etiology. An hepato-pulmonary syndrome developed
      which was reversible following liver transplantation.

PMID- 9522306
TI  - [Paralysis of the superior laryngeal nerve after whiplash trauma].
AB  - BACKGROUND: The current literature rejects the possibility of strain of the
      superior laryngeal nerves by whiplash injury. However, due to the anatomic
      situation and the mechanism of the whiplash injury this damage does not seem
      unlikely. PATIENT: A 58-year-old male patient, who was a trained singer,
      complained of a loss of his head voice following a major whiplash injury.
      Indirect laryngoscopy revealed no unusual findings. The phoniatric examination
      showed a loss of the head voice in the vocal field indicating paresis of the
      superior laryngeal nerves. Three and one-half months after the whiplash injury,
      the paresis had completely receded and the patient had a voice well above average
      with an excellent frequency range. CONCLUSIONS: In the case presented the paresis
      of the superior laryngeal nerves could have been caused by a strain of the nerves
      during whiplash injury. A complete and exact phoniatric diagnosis can be
      recommended for elderly patients complaining of an altered voice following
      whiplash injury.

PMID- 9522307
TI  - [External vocal fold medialization: surgical experiences and modifications].
AB  - BACKGROUND: Despite a first report as early as 1915 by Payr, vocal fold
      medialization by an external approach did not gain general acceptance for many
      decades. Only when Isshiki took up these first attempts again in the 1970s,
      fundamentally revised them, and expanded the methods into the groups of Laryngeal
      Framework Surgery and Thyroplasty, did these techniques spread. Now they are
      increasingly performed. We have been using this technique since 1991. In a
      retrospective study we critically reviewed surgical experience with the original
      technique and several newly developed surgical modifications. PATIENTS: An
      external vocal fold medialization was performed in 53 patients (22 male, 31
      female). The underlying cause for the glottic insufficiency was in most of the
      cases unilateral laryngeal palsy, predominantly caused by thyroid surgery. Ten
      patients presented with an atrophy and/or scar of the vocal folds. In 7 out of
      these 10 cases the vocal folds were mobile. Most of the patients were operated on
      (n = 32) using the Isshiki technique. In the remaining 21 patients surgical
      modifications were used. In 7 cases new developed implants made out of glass
      ionomer cement were used, in 5 patients vocal fold medialization was performed
      using a 0.25 mm titanium sheet. RESULTS: No intraoperative or postoperative
      complications could be observed. The surgical procedure was very well tolerated
      by all patients. The degree of glottic insufficiency was significantly reduced.
      There was also a statistically significant correlation between the preoperative
      and the postoperative degrees of glottic insufficiency. It was not always
      possible to close large glottic gaps completely in every case. Despite good
      overall results we experienced some limitations of the implant and the surgical
      technique as well. We therefore began to modify the implant and the surgical
      technique on the basis of anatomic and experimental studies. CONCLUSIONS:
      External vocal fold medialisation proved to be a safe and well tolerated surgical
      procedure. It is reversible and revisable, suitable for nearly all kinds of
      glottic insufficiencies, and can be combined with other phonosurgical procedures.
      Significant reduction of glottic insufficiency can usually be achieved, although
      large glottic gaps cannot be closed completely in every case. It should be
      possible to overcome certain limitations of the currently performed technique by
      developing new implants and modified surgical procedures. External vocal fold
      medialisation could then become established as a standard procedure providing
      even better and more stable functional results, at minimal risk to the patient.

PMID- 9522309
TI  - [Clinical and molecular biology studies of laryngeal papillomatosis].
AB  - BACKGROUND: Recurrent laryngeal papillomatosis is a benign neoplastic disease
      which is probably caused by but at least associated with the Human Papilloma
      Virus. It can be of significant importance for the affected patients because of
      its recurrent clinical course. A wide variety of therapeutic measures have been
      described including the surgical removal either with conventional instruments or
      laser. Malignancies developing from papillomas have been reported. PATIENTS: The
      clinical courses of all 95 patients who have been treated for laryngeal
      papillomatosis since 1960 were analysed retrospectively. The two most common
      forms of treatment, surgical removal either conventionally or with the use of the
      laser, were compared. "Hot-start" polymerase chain reaction and Southern blot
      hybridization were used to detect HPV-DNA. The case reports of all patients
      developing cancer of the larynx are included. RESULTS: Laryngeal papillomatosis
      is a disease of all ages, more often first diagnosed before age 10 or after age
      30. Puberty had no effect on the clinical course. However, the rate of
      complications such as tracheostomy and glottic webs was significantly reduced
      after laser surgery. HPV-DNA was found in 10 of 11 samples. Squamous cell
      carcinoma subsequently developed in four cases, three of which occurred almost
      simultaneously and were therefore not included. CONCLUSION: The term juvenile
      laryngeal papillomatosis should be replaced by recurrent respiratory
      papillomatosis. The occurrence of squamous cell carcinomas in patients previously
      treated for papillomas underlines the need for repeated histological studies. The
      surgical treatment remains the mainstay in the management of laryngeal
      papillomatosis. The laser surgical technique is superior to conventional removal.
      Using the most sensitive and specific methods presently available, HPV-DNA can be
      detected in a large percentage of laryngeal papillomas.

PMID- 9522308
TI  - [External vocal cord medialization: functional outcome].
AB  - BACKGROUND: Comprehensive evaluation of voice function is the precondition for
      indication and quality control of every phonosurgical procedure. In 53 patients
      presenting with glottic insufficiencies of different etiologies an external vocal
      fold medialisation was performed. Functional voice results obtained with this
      operation are presented and discussed. METHODS: The following voice parameters
      were measured preoperatively and postoperatively, and statistical comparison was
      performed: mean fundamental frequency and sound pressure level, frequency and
      intensity range (voice range profile), perceptual evaluation of hoarseness, and
      maximum phonation time. The impairment of vocal communication skills was rated on
      a newly developed 7-point scale. A combined parameter called "Voice Dysfunction
      Index" was introduced for global assessment of vocal abilities in particular for
      long term observations. RESULTS: Statistically significant improvement of all
      voice parameters was demonstrated. Interestingly, in nearly all measurements male
      patients yielded significantly better results than females. Glottic
      insufficiencies due to scarring produced poorer functional results but without
      statistical significance. A statistically significant correlation between the
      preoperative and postoperative Voice Dysfunction Index could be observed. This
      score was also significantly correlated with the degree of glottal gap. No
      significant correlation between voice results and preoperative delay or follow-up
      period were observed. Voice therapy was performed in 81% of the patients.
      Correlation of duration of voice therapy and voice results was statistically
      significant and negative. Analysis of this surprising result showed that it was
      caused by some patients with vocal fold scarring in whom outcome was poor despite
      a long period of voice therapy. CONCLUSIONS: Significant improvement of vocal
      function can be obtained by external vocal fold medialization in patients with
      glottic insufficiencies. Glottal gaps caused by vocal fold scarring and/or
      atrophy can be treated with this method, too. However, results are not as good as
      in paralysis and require additional long term voice therapy. Satisfying results
      can be expected in patients with a long history of disturbances, and in older
      patients. Due to the reversibility of the operation, external vocal fold
      medialization can be performed even in cases of palsy prior to the spontaneous
      recovery period. The degree of glottic gap determines the functional disturbance.
      The degree of the preoperative impairment correlates with the outcome. Results
      are stable with respect to the follow-up period (mean 66 weeks).

PMID- 9522310
TI  - [Cytokine pattern in various forms of sinusitis].
AB  - BACKGROUND: Inflammatory sinus diseases include acute sinusitis, chronic purulent
      sinusitis, and chronic polypoid rhinosinusitis. We investigated the cytokine
      profile of different types of rhinosinusitis in order to evaluate whether a
      distinct form of rhinosinusitis is associated with the expression of a specific
      cytokine profile. METHODS AND PATIENTS: Fresh sinus mucosa obtained during
      routine surgery from patients with acute sinusitis (n = 10), chronic sinusitis (n
      = 7), antrochoanal polyp (n = 10), nasal polyps (n = 8), and controls of
      turbinate mucosa (n = 7) were homogenized. The cytokine protein content (IL-1
      beta,IL-3,IL-5,IL-6,IL-8,GM-CSF) of tissue homogenates was measured using ELISA
      technique. RESULTS: In the group of proinflammatory cytokines, the protein levels
      measured for interleukin IL-8, a proinflammatory cytokine, IL-1 beta, and IL-6
      were elevated in acute sinusitis. In the group of eosinophil-activating cytokines
      interleukin-3, -5 and granulocyte an makrophage-colony stimulating factor, we
      measured a significantly elevated protein level of IL-5 in nasal polyp tissue in
      contrast to significantly elevated IL-3 protein level in chronic sinusitis.
      CONCLUSIONS: These findings suggest that IL-8 plays a pivotal role in neutrophil
      dominated and IL-5 in eosinophil-dominated sinusitis. IL-3 seems to sustain
      chronic inflammation.

PMID- 9522311
TI  - [Epithelialization of titanium prostheses in the middle ear of the rabbit.
      Possible model of mucosa development].
AB  - BACKGROUND: The epithelialization of middle ear implants is regarded as a sign of
      biocompatibility of the implant material. METHODS: The mucosal coverage of
      titanium was studied in the middle ear of rabbits in light microscopy. Implants
      were used as middle ear prostheses or as a free implants. Studies were performed
      after 28, 84, 168, 336, and 504 days. RESULTS: The prostheses were seen to be
      covered by regular mucosa after 28 days. The free implants were not seen to be
      totally epithelialized even after 504 days. There were no inflammation cells on
      the surface of the material, nor were unusual amounts of fibrous tissue observed.
      The middle ear mucosa was initially thickened, but soon returned to normal
      values. CONCLUSIONS: The results of this animal experiment show that titanium is
      a suitable material for ossicular replacement.

PMID- 9522312
TI  - [Re-amplification of differentially expressed mRNA fragments of head-neck cancers
      without cloning].
AB  - BACKGROUND: mRNA expression of healthy and malignant cells can be compared to
      each other by employing the "differential display" (DD) technique. Most studies
      describe sequence analysis of differentially expressed fragments after
      reamplification by a second round of PCR and subsequent molecular cloning to gain
      a sufficient amount of DNA for sequencing. The aim of this study was to show
      whether a sufficient amount of differentially expressed mRNA of squamous cell
      carcinoma cells of the head and neck region can be generated by PCR alone without
      cloning steps. MATERIAL AND METHODS: mRNA isolated from cultivated keratinocytes
      and squamous cell carcinoma cells was reverse transcribed into cDNA which was
      amplified with PCR. Differentially expressed fragments detected after gel
      electrophoresis were isolated from the gel and reamplified in a second PCR. The
      resulting cDNA amounts of the second PCR were suitable for cloning but not for
      direct sequencing. A third round of PCR with the undiluted final product of the
      second PCR as template regularly failed. Dilutions of the second PCR products
      between 1:10 and 1:10(10) were prepared. The third round of PCR was carried out
      with these various template concentrations. RESULTS: A sufficient amount of
      differentially expressed fragments for sequencing procedures resulted when
      dilutions of the second PCR products ranging from 1:10(2) to 1:10(7) were used as
      templates in the third round of PCR. CONCLUSION: Modifications of PCR parameters
      provide high DNA copy numbers of differentially expressed mRNA fragments from
      squamous cell carcinoma cells of the upper aerodigestive tract in amounts that
      are needed for sequence analysis. This may make it possible to avoid labor
      intensive cloning procedures requiring high safety standards.

PMID- 9522314
TI  - [Elevatorium for fractures of the nasal bone and zygomatic arch].
AB  - BACKGROUND: Unsuitable instruments are often used for the reduction of nasal
      fractures and fractures of the zygomatic arc. A new instrument for elevation and
      reduction of these common fractures is presented. METHOD: The special shape of
      the elevator, which is adapted to the anatomy of the nasal dome, is helpful in
      nasal surgery. The bayonet-shaped angle also allows elevation of compressed
      fragments of the zygomatic arc. RESULTS: This instrument was successfully used in
      the reduction of 107 bony fractures of the nose and 36 fractures of the zygomatic
      arc. CONCLUSION: From the clinical point of view the elevator can be recommended
      for ENT specialist working in a trauma setting.

PMID- 9522313
TI  - [Is there a correlation between sudden deafness and smoking?].
AB  - BACKGROUND: The etiology of sudden hearing loss is not yet known. The most common
      mechanism of sudden hearing loss would appear to be impaired cochlear blood
      circulation. Tobacco smoking causes changes in hemostasis and raises the body's
      need for oxygen because of carbon monoxide, one component of the smoke which
      blocks a part of the hemoglobin. PATIENTS AND METHODS: 297 patients (76 smokers,
      99 former smokers, and 122 non smokers) who were treated because of sudden
      hearing loss in the hospital in the last 5 years were queried about their smoking
      habits. We asked the patients to complete a questionnaire in order to get more
      reliable answers. We explored the kind of tobacco, the number of cigarettes or
      cigars per day, the age at onset of smoking, the number and rate of recurrence of
      sudden hearing loss, the result of the treatment of a former sudden hearing loss
      (if there was one), the characteristics of tinnitus, the possibility of stopping
      smoking, and the significance of tobacco smoking as reflected in health policy.
      RESULTS: Tobacco smoking does not increase the overall risk of sudden hearing
      loss. The incidence of smokers in the population of the region and the incidence
      of smokers among patients with sudden hearing loss is equal. But the average age
      of the smoking patients is significantly lower than the average age of non
      smokers and former smokers. Smokers have a higher rate of recurrence of a sudden
      hearing loss. The result of treatment of former sudden hearing loss is worse in
      smoking patients. CONCLUSIONS: There is no obvious relation between the risk of
      sudden hearing loss and tobacco smoking.

PMID- 9522315
TI  - [Diagnosis and therapy of tinnitus].
AB  - INTRODUCTION: Tinnitus is still one of the most frequent symptoms encountered by
      the otorhinolaryngologist. Diagnosis and therapy present high demands due to the
      complex etiology and secondary symptoms. PATHOPHYSIOLOGY: In contrast to
      objective ear ringing with a physical sound source near the ear, tinnitus is
      faulty coding within the auditory system. Damage due to all kinds of causes can
      lead to a change of spontaneous activity in the auditory system. The result is a
      subjective auditory impression which is increased by further learning processes.
      DIAGNOSTICS: The aim of otorhinolaryngologic and especially audiologic diagnostic
      studies is to find the cause of the tinnitus. Modern methods for the
      objectivation of tinnitus are still experimental. The psychosomatic diagnostic
      studies evaluate secondary symptoms. THERAPY: Acute tinnitus is treated like
      sudden deafness. For chronic forms, the analysis of the causes is particularly
      important for developing an individual consultation and therapy plan. Providing
      information of the patient is the first step for a sensible treatment of the
      symptoms. The retraining therapy represents a learning process to reduce
      subjective symptoms, inconvenience, and loudness. Supportive therapy includes the
      use of instrumentation and medication. CONCLUSION: Acute tinnitus is often
      curable. However, only palliative treatment is available for chronic tinnitus.
      The otorhinolaryngologist plays a crucial role in the management of the disorder.

PMID- 9522316
TI  - [Interesting case no. 9. Esthesioneuroblastoma (olfactory neuroblastoma)].

PMID- 9522317
TI  - [Reconstructive interventions].

PMID- 9522318
TI  - Urogenital and vasomotor symptoms in relation to menopausal status and the use of
      hormone replacement therapy (HRT) in healthy women during transition to
      menopause.
AB  - OBJECTIVE: To investigate the relationship between climacteric status, hormonal
      levels, vasomotor symptoms, vaginal dryness and urinary incontinence in a cohort
      of healthy women during transition to menopause, and further to evaluate the
      effects of hormone replacement therapy on these symptoms. METHODS: A total of 147
      women were followed for 4 years during transition to menopause. They were all 49
      years old when entering the study. Each annual visit included a general health
      screening, gynecological examination and blood sampling. The subjects were
      questioned about sociodemographic background, obstetric and gynecological history
      and they kept bleeding diary cards. RESULTS: Urinary incontinence was reported by
      57% at the first visit and decreased to 34% at the last visit. No correlation to
      hormonal levels or to the use of HRT (hormone replacement therapy) was seen, but
      parity was significantly (P = 0.05) correlated to urinary incontinence. Vaginal
      dryness occurred in 37% at the first visit. Vaginal dryness was experienced by
      1/3 of the premenopausal women. Vasomotor symptoms were reported by 56% at the
      first visit and were associated with high levels of FSH and LH (P < 0.001 and P =
      0.002, respectively). One third of premenopausal women reported on vasomotor
      symptoms. Hormone replacement therapy did not relieve hot flushes in these women.
      CONCLUSIONS: Urogenital and vasomotor symptoms experienced by premenopausal women
      do not seem to be relieved by hormone replacement therapy.

PMID- 9522319
TI  - Continuous versus cyclical transdermal estrogen replacement therapy in
      postmenopausal women: influence on climacteric symptoms, body weight and bleeding
      pattern.
AB  - OBJECTIVES: To compare continuous and cyclical transdermal estrogen replacement
      therapy (ERT) with or without an oral progestogen regarding climacteric symptoms,
      body weight and bleeding pattern. METHODS: A total of 2459 postmenopausal women
      were treated for three cycles of 28 days in an open, randomized, parallel group
      multicenter study. Patients received an estrogen matrix patch (50 micrograms
      17/beta-estradiol/day) twice weekly, either continuously (eight patches/cycle) or
      cyclically (six patches/cycle, i.e. 3 weeks on, 1 week off). A total of 1232
      patients were treated continuously and 1227 cyclically. In the study group 1150
      patients had an intact uterus (543 in the continuous and 607 in the cyclical
      treatment arm) and received, in addition to the estrogen patch, an oral
      progestogen in a transformation dose for 12 days of each cycle. Hysterectomized
      patients totaling 1309 (689 in the continuous versus 620 in the cyclical group)
      did not receive progestogen. Of the 2459 patients, 771 (31.4%) participated in a
      follow-up study with two further treatment cycles, which was offered to the
      patients at the end of the main study. The main outcome measures were climacteric
      symptoms, measured at the end of cycles 1-3 by a Visual Analogue Scale at
      baseline, and body weight measured at baseline at the end of cycles 3 and 5. In
      addition, the bleeding time per cycle (days) was evaluated in all patients with
      an intact uterus. RESULTS: Continuous and cyclical transdermal ERT reduced, over
      three treatment cycles, the average climacteric symptom score by 1.77 and 1.70,
      respectively. The percentage remission and improvement rates for the ten
      climacteric symptoms ranged between 69.3 and 88.0% and did not differ between the
      two groups. In patients with a higher symptom score at baseline, the continuous
      treatment was slightly more effective. However, this effect was statistically not
      significant. After three treatment cycles body weight increased in both treatment
      groups by between 500 and 700 g. Further treatment during the follow-up study
      induced an additional average weight gain of 200-400 g. These results were not
      influenced by the addition of an oral progestogen. In patients with an intact
      uterus, the average bleeding time at the end of the first cycle (5.4 days in the
      continuous versus 5.3 days in the cyclical group) increased slightly during cycle
      2 and returned to baseline values at the end of cycle 3. CONCLUSIONS: Continuous
      and cyclical transdermal ERT were equally effective in reducing climacteric
      symptoms. The short term use of five cycles transdermal ERT induced a slight
      increase in body weight which was independent of the treatment regimen. These
      results were not influenced by the type and mode of administration of a
      progestogen. Both ERT regimens were very well tolerated and are suitable
      alternatives for estrogen replacement therapy of postmenopausal women.

PMID- 9522320
TI  - Neuroendocrine effects of different estradiol-progestin regimens in
      postmenopausal women.
AB  - OBJECTIVE: New regimens and routes of administration of hormonal replacement
      therapy (HRT) in climateric women are becoming available. Since there is no
      information on the neuroendocrine effects of sequential combined treatment with
      17 beta-estradiol and a progestin, the present study evaluated the
      neuroendocrine, clinical vasomotor and psychological changes before and after
      different sequential combined HRT regimens (17 beta-estradiol plus nomegestrol
      acetate, or cyproterone acetate, or vaginal progesterone). Vasomotor and
      behavioral effects were evaluated by using the Kupperman score, while changes in
      plasma endorphin (beta-END) levels were used as marker of neuroendocrine effects.
      METHODS: Postmenopausal women (n = 30) were randomly divided into three groups
      (ten women for each group); all women received continuous 17 beta-estradiol (50
      mg, transdermal) and each group was sequentially treated with different
      progestins for 12 days/month: group A, cyproterone acetate (5 mg p.o.); group B,
      nomegestrol acetate (5 mg p.o.); and group C, progesterone (100 mg, vaginal
      cream). A group of healthy fertile women (n = 8) served as control. Before and
      after 6 months of HRT, postmenopausal women underwent an evaluation of subjective
      Kupperman score and two neuroendocrine tests: (a) naloxone (4 mg i.v.) and (b)
      clonidine (1.25 mg i.v.). Plasma beta-END levels were measured before and at 15,
      30, 45, 60 and 90 min after drug injection. Control women were studied by
      administering the two neuroendocrine tests only once. RESULTS: Postmenopausal
      women before HRT showed a pathological Kupperman and no changes of plasma beta
      END levels in response to the clonidine and naloxone tests score. On the contrary
      the increase was significant in healthy women. In each of the three groups of
      treated women both naloxone and clonidine tests induced a significant increase in
      plasma beta-END levels (P < 0.01). After 6 months of HRT, an improvement of
      vasomotor and psychological symptoms was shown by a decrease of Kupperman score.
      CONCLUSIONS: The present study indicates that sequential treatment with
      transdermal 17 beta-estradiol and progestin, no matter which progestin was used,
      restores the beta-END release, improves vasomotor and psychological symptoms.

PMID- 9522321
TI  - Improving compliance with hormonal replacement therapy in primary osteoporosis
      prevention.
AB  - OBJECTIVES: To evaluate whether introduction of treatment alternatives would
      improve compliance with hormonal replacement therapy (HRT) as primary
      osteoporosis prevention in women not tolerating the first line osteoporosis
      prevention schedule. MATERIAL AND METHODS: Follow-up in four hospitals
      participating in the Danish Osteoporosis Prevention Study. A total of 706 peri-
      and postmenopausal women aged 45-57 years between 3 and 24 months from last
      menstrual bleeding took part, 489 women were randomised to HRT and 217 received
      HRT by personal choice. A total of 135 (19%) women were hysterectomised. HRT was
      given as oral or transdermal oestradiol supplemented with progestogen. If the
      initial treatment allocation was not acceptable several alternatives were
      available in a pragmatic approach. RESULTS: Compliance with first treatment
      schedule was lower in women with intact uterus (at 5 years: 48.3 +/- 2.4%
      compliance) than in hysterectomised (64.7 +/- 5.8%, P < 0.001 in a Cox analysis)
      but did not differ after the introduction of HRT alternatives (67.0 +/- 2.9 vs
      77.8 +/- 5.9, P = 0.12). Compliance decreased with increasing age at treatment
      start (RR = 1.11, P < 0.001) in women with intact uterus but not in
      hysterectomised women (P = 0.96). Headache/migraine was more frequent among women
      with intact uterus on oral sequential oestrogen plus progestogen than among
      hysterectomised women receiving oral continuous oestrogen (RR = 11.3, P < 0.01).
      CONCLUSIONS: It seems possible to maintain a high HRT compliance by a pragmatic
      approach including offering alternative HRT formulations to women not tolerating
      the primary HRT. Further research into long-term compliance with HRT and cost
      benefit is warranted.

PMID- 9522322
TI  - Effects of nasal administration of calcitonin in oophorectomized women: 2-year
      controlled double-blind study.
AB  - OBJECTIVE: The aim of this study was to assess the effects of nasal salmon
      calcitonin (SCT) administration on bone turnover in ovariectomized women.
      METHODS: Patients who had undergone bilateral ovariectomy 7 days previously,
      received either calcium supplementation (1000 mg/day, together with nasal SCT
      (100 IU/day) (n = 19) or the same calcium supplementation together with a placebo
      intranasal spray daily (n = 19), for 2 years. RESULTS: In the calcium-only
      treated subjects, lumbar bone mineral density (BMD) was found to have decreased
      significantly (P < 0.001), 6 months after surgery and remained at this level
      until the end of the study. In the SCT-treated group, BMD remained stable during
      the 1st year and then decreased gradually, reaching a statistically significant
      level in the 2nd year. Mean serum osteocalcin concentration was unchanged during
      the 1st year of SCT treatment but was significantly elevated during the 2nd year
      (P < 0.01). The observed rise in serum osteocalcin concentration and urinary
      hydroxyproline excretion during the 2nd year of treatment with SCT was
      accompanied by a significant rise in serum calcitonin levels (P < 0.001 after 18
      months and P < 0.01 after 24 months). CONCLUSION: This study shows that
      continuous treatment with intranasal SCT is able to prevent the bone loss that
      follows ovariectomy.

PMID- 9522324
TI  - The effect of transdermal 17-beta-estradiol on glucose metabolism of
      postmenopausal women is evident during the oral but not the intravenous glucose
      administration.
AB  - OBJECTIVES: To evaluate the effect of transdermal 17-beta-estradiol (50
      micrograms/day) on glucose metabolism of postmenopausal women. STUDY DESIGN: A
      frequently sampled intravenous glucose tolerance test (FSIGT), to calculate
      insulin sensitivity (SI) and peripheral glucose utilization independent of
      insulin (SG), and an oral glucose tolerance test (75 g; OGTT), were performed in
      nine postmenopausal women prior to, and after 2 months of, treatment. RESULTS:
      Estradiol decreased insulin and increased the C-peptide/insulin ratio both during
      fasting (P < 0.02) and OGTT (insulin levels, P < 0.01; C-peptide/insulin ratio, P
      < 0.05), but not FSIGT. Glucose levels, C-peptide levels, SI and SG were not
      affected. CONCLUSIONS: In spite of unmodified SI, the reduction of insulin levels
      and the increase of the C-peptide/insulin ratio, observed during fasting and
      OGTT, support a beneficial effect of estradiol on glucose metabolism. This effect
      probably requires the interplay of estradiol with gastrointestinal factors.

PMID- 9522323
TI  - Continuously combined hormone replacement therapy and bone turnover: the
      influence of dydrogesterone dose, smoking and initial degree of bone turnover.
AB  - In this study we examined whether the effect of continuously combined hormone
      replacement therapy (HRT) on bone metabolism is influenced by dydrogesterone
      dose, smoking and initial degree of bone turnover. In a double-blind randomized
      study, 123 healthy postmenopausal women (mean age 51.7 years; range 30-61 years)
      received 17 beta-estradiol, 2 mg orally per day, continuously combined with
      either 2.5, 5, 10 or 15 mg of dydrogesterone daily. At baseline and at 3 and 6
      months of therapy, bone formation was assessed by determining total alkaline
      phosphatase (TAP), bone-derived alkaline phosphatase (BAP), and the carboxy
      terminal propeptide of collagen type I (PICP) in serum; bone resorption was
      assessed by the calcium/creatinine (Ca/Creat) and hydroxyproline/creatinine
      (Hp/Creat) ratio in 2-h fasting urine, and the serum carboxy-terminal
      pyridinolyne cross-linked telopeptide of collagen type I (ICTP). Dydrogesterone
      dose did not influence the effect of HRT on any of the bone markers. Combining
      the data of the four treatment groups, the decrease in each marker, compared to
      baseline values, was significant. However, in non-smokers, compared to smokers,
      after 6 months of therapy the decline in BAP and TAP was significantly more
      pronounced and the plasma estradiol level was significantly higher. For each
      bonemarker at baseline, women in the highest quartile, compared to women in the
      lowest quartile, showed a significantly stronger decrease in this marker in
      response to HRT. We conclude that dydrogesterone dose does not modify the
      effectiveness of replacement therapy. However, smoking and a low bone turnover at
      baseline may diminish its beneficial effect on bone.

PMID- 9522325
TI  - A comparative study of two levonorgestrel-containing hormone replacement therapy
      regimens of efficacy and tolerability variables.
AB  - OBJECTIVE: To compare the effect of two sequential hormone replacement regimens
      differing in the dose of levonorgestrel on climacteric symptoms, bleeding pattern
      and lipid metabolism in postmenopausal women. STUDY DESIGN: In a multicentre,
      randomized, double-blind, active-treatment-controlled study, 210 postmenopausal
      women were assessed at the end of treatment cycles 3 and 6. The high
      levonorgestrel group was treated with 2 mg estradiol valerate (days 1-21)
      sequentially combined with 0.25 mg levonorgestrel (days 12-21). The low
      levonorgestrel group received the same estrogen regimen (2 mg estradiol valerate,
      days 1-21), but levonorgestrel was administered sequentially in a dose of 0.15 mg
      during the last 12 days of the cycle (days 10-21). Statistical analysis by
      Student's t-test for dependent variables (measured values versus baseline) and
      independent variables (differences between groups), and the composite t-test
      method for comparison of both regimens with respect to efficacy, was performed.
      RESULTS: Both groups were statistically comparable. The trial was completed by
      137 subjects. Protocol violations occurred in 38 cases. Thirty-five subjects
      dropped out during the study, 21 of them because of adverse events. Both
      treatments were equally effective in the treatment of climacteric complaints.
      There were no clinically significant changes in body weight, blood pressure,
      haematological tests, and parameters of clinical chemistry. There was a tendency
      towards a reduction in bleeding intensity in both groups in the second half of
      the treatment period. The treatment for six cycles with both regimens
      significantly (P < 0.05) decreased plasma concentrations of triglycerides
      (significant in the low-levonorgestrel group only), high-density lipoprotein
      cholesterol, high-density lipoprotein-3-cholesterol, lipoprotein(a) and
      apolipoprotein A1. In parallel, the serum concentration of total cholesterol
      increased significantly in both treatment groups, whereas low-density lipoprotein
      cholesterol increased significantly in the high-levonorgestrel group only. The
      changes in high-density lipoprotein-2-cholesterol, and apolipoprotein B did not
      reach statistical significance. CONCLUSIONS: It can be concluded that both
      sequential combined oral hormone replacement therapy (HRT) regimens were
      equivalent with respect to efficacy and tolerability in the treatment of women
      with climacteric complaints. The preparation with the lower dose of progestin
      showed a tendency towards a less unfavourable influence on the lipid profile.

PMID- 9522326
TI  - Mechanisms of relaxation of rat aorta in response to progesterone and synthetic
      progestins.
AB  - OBJECTIVE: To compare the acute effects of progesterone, chlormadinone acetate
      (CMA), norethisterone acetate (NETA) and dienogest (DNG) with those of 17 beta
      estradiol (17 beta-E2) on the vascular reactivity of male rat thoracic aorta.
      METHODS: Aortic rings with or without endothelium were placed in an organ bath
      for isometric tension recording. The integrity of the endothelium was assessed by
      the relaxant response of precontracted rings to acetylcholine (1 and 10 microM),
      which was diminished after mechanical removal of the endothelium. The
      concentrations of the steroid hormones were 0.01-10 microM. RESULTS: In vessels
      precontracted with phenylephrine (1 microM), CaCl2 (3 mM) or KCl (30 mM),
      progesterone, CMA and NETA (10 microM each) an endothelium-independent relaxation
      of 20-35% resulted, with a maximum response after 20-30 min, while DNG had a
      negligible effect in all experiments. The same concentration of 17 beta-E2 was
      twice as potent as the progestins. Indomethacin, the cyclooxygenase inhibitor and
      glibenclamide, an inhibitor of the ATP-sensitive potassium channels, did not
      affect the relaxant responses. The antagonists of progesterone receptors J 867 (1
      microM) as well as of estrogen receptors ICI 182780 (1 microM) did not counteract
      the relaxation induced by progesterone and 17 beta-E2, respectively. Progesterone
      (10 microM) did not interfere with endothelium-dependent acetylcholine-induced
      relaxation of precontracted aortic rings. Pretreatment of the vessels with the
      hormones attenuated the maximal contractile response to phenylephrine. In the
      presence of verapamil (1 microM) or progesterone (10 microM) or 17 beta-E2 (1 and
      10 microM) the concentration-response curves for calcium-induced contractions in
      K(+)-depolarized vessels were shifted to the right, with suppression of the
      maximum response. CONCLUSIONS: These studies suggest that in addition to 17 beta
      E2 the progestins, progesterone, CMA and NETA caused a reduction of vascular
      tone, probably due to blockade of voltage-dependent and/or receptor-operated
      calcium channels.

PMID- 9522327
TI  - [Psychopharmacotherapy during pregnancy and lactation. 1: Pregnancy].
AB  - Approximately one-third of all pregnant women take psychotropic drugs at least
      once during pregnancy. At the same time, there are no preparations on the market
      that can be considered entirely appropriate for expectant mothers. The effects of
      psychopharmacological therapies have exclusively been discussed in the context of
      their risk during the first trimester. However, treatment after this phase is not
      absolutely without risk, and it is striking that there are grave differences
      between various substances. There are currently controversial discussions going
      on in literature as far as the teratogenicity of lithium is concerned, especially
      during the formation of the heart. It is suggested that the risk for congenital
      malformations is increased after intrauterine lithium exposure, whereas such a
      risk cannot be proved for most of the antidepressants and neuroleptics. Still, it
      should be noted that psychopharmacology is not harmless even after the
      organogenesis, as intrauterine exposure during the 2nd and 3rd trimester can lead
      to postnatal complications. For example, floppy-infant syndrome after taking
      benzodiazepines, and the extrapyramidal-motor effects on the newborn after
      neuroleptic therapy during pregnancy should be mentioned.

PMID- 9522328
TI  - [Psychopharmacotherapy in pregnancy and lactation. 2: Lactation].
AB  - Whilst the incidence of psychiatric disorders decreases during pregnancy, the
      risk during the postpartum period increases significantly, often leading to the
      necessity of psychopharmacological intervention during the puerperium, and
      subsequently during lactation and breast-feeding. The necessity for lithium
      prophylaxis in manic-depressive women after childbirth has been identified, and
      it is recommended that weaning rather than omission of psychopharmacological
      treatment is preferable during the puerperium.

PMID- 9522329
TI  - [Electroconvulsive therapy in psychiatric clinics in Germany in 1995].
AB  - A total of 451 German psychiatric hospitals were asked in 1995 about their use of
      electroconvulsive therapy (ECT). As ECT nowadays is well accepted as a
      therapeutic tool, we wanted to compare our data with data collected in former
      inquiries in 1977 and 1985 and to acquire information from the new German States.
      Since 1977, the use of ECT has evidently increased. The psychiatric hospitals
      that often use ECT are for scattered throughout the whole country. ECT is mainly
      indicated for febrile catatonia/febrile stupor and depressive stupor, not for
      schizophrenia. ECT is applied especially when depressive patients are resistant
      or intolerant of psychopharmacotherapy. The preparation and application
      correspond to the standards. One focus in the present study was the attitudes of
      the managing directors towards ECT. Data were collected by open questionnaires.
      When these data were compared with data from a standardized inquiry of 1985, a
      similar trend was found regarding positive statements about ECT. Statements are
      emphasized even more when using open questionnaires. If there is a strong
      indication for ECT, the basic attitudes of the managing directors toward ECT are
      very positive. However, its application is in fact much more influenced by social
      factors than by indication because of negative attitudes by colleagues and
      nursing staff and political and stereotypic thinking of the general population.

PMID- 9522330
TI  - [Depression in the very elderly].
AB  - In the Berlin Aging Study (BASE) an age and gender stratified sample of 516
      persons aged 70 to over 100 was assessed by means of the semi-structured GMS-A
      interview, the CES-D-self-rating scale and the Hamiltion-Depression-observer
      rating scale. Prevalence rates were 4.8% for Major Depression, 9.1% for all DSM
      III-R specified depressive disorders and 26.9% of subthreshold depression was
      included. There was no increase in prevalence rates with age but an increase in
      scores on the self rating CES-D. The prevalence rates for DSM III-R specified
      depression in females was 10.3% and almost double that of men (5.6%). Depressed
      persons do not show significant cognitive impairment as measured with the MMSE in
      comparison to controls. As compared to the total sample higher prevalence rates
      of overall depression were seen in persons with multimorbidity (36.8%) and lower
      rates in married persons. 13.2% of the elderly talked about feeling tired with
      life, 7.9% had thoughts about death and 1.2% reported suicidal ideation, which
      was closely linked to depressive disorders. In 44% of depressed cases
      undertreatment was observed. Only 6% got Antidepressants but 40% benzodiazepines.

PMID- 9522331
TI  - [Time perception and time estimation in depressive patients].
AB  - Subjective time-experience and objective time-estimation were examined in 20
      endogenous, 20 neurotic depressives, and 15 healthy volunteers. Subjective
      experience of past and anticipated future time was more extended in both
      depressive groups than in healthy controls. Objective time estimation differed
      between depressives and controls concerning relatively long time spans whereas
      very short time spans were correctly estimated also by depressives. There were no
      significant differences between endogenous and neurotic depressives. The
      perception of extended time normalized during treatment. The depressives' time
      perception, differences correlated with the extent of depressive
      psychopathological symptoms and--to a lesser degree--with retardation. The
      findings support the hypotheses of anthropological phenomenology concerning
      disturbed time perception and estimation in depressives. Amelioration of
      experienced time-extension in intentionally structured time spans compared to
      empty time spans suggests psychotherapeutic consequences in the sense of
      Lewinsohn.

PMID- 9522332
TI  - [Risk factors for recurrence in bipolar manic-depressive patients].
AB  - A prospective multidimensional study with 71 remitted bipolar outpatients (37
      bipolars without, 34 with psychotic symptoms during acute mania) was made to
      assess relevant influential factors on relapse and readmission to hospital:
      characteristic data of previous course, psycho(patho)logical state and
      personality after remission, personality disorders, and ways of coping. In the
      course of the 5 years after the first examination, 48% of the patients were
      readmitted, 60% of them because of a (schizo)manic state. The study confirms the
      prognostic relevance of past course, e.g. number of previous episodes and mania
      quotient. A further risk-factor are residual psychopathological alterations which
      persist after remission ("negative symptoms" of strictly bipolars, increased
      vulnerability for dynamic derailment for the bipolars with psychotic symptoms).
      Patients with "syntonic" personality in the free interval suffered less relapses.
      The relevance of other personality traits differed in the diagnostic subgroups of
      nonpsychotic and psychotic bipolars. Active coping was positively correlated with
      staying healthy, but the correlations were weak.

PMID- 9522333
TI  - ["I have killed my child". Experiences with severe depression in mothers after
      sudden infant death from the psychiatric and legal medicine viewpoint].
AB  - Grief and depressive syndrome belong to normal reaction by parents after a sudden
      infant death (SID). In the following we report on two cases from the point of
      view of psychiatry and forensic medicine in which, subsequent to SID, mothers
      reacted with extremely grave depression and accused themselves of having killed
      the child. Furthermore, some recommendations are given for the care of parents
      affected.

PMID- 9522334
TI  - [Inpatient treatment of depressed patents. Conceptual considerations and results
      of a pilot project for quality assurance in Baden-Wurttemberg].
AB  - Quality-assurance activities will become more important in psychiatry during the
      next few years. In relation to other medical disciplines, some special aspects
      concerning structure, process and outcome quality as well as practical
      realization and methodologic aspects must be considered. These specific issues
      were the focus of a study dealing with the treatment of depressed inpatients. The
      experiences and results as well as considerations concerning future quality
      assurance projects are discussed.

PMID- 9522335
TI  - [Sleep deprivation and subsequent sleep phase advance stabilizes the positive
      effect of sleep deprivation in depressive episodes].
AB  - Approximately 60% of patients with major depression disorder show a beneficial
      response to total sleep deprivation (TSD), but the positive effect of TSD is
      short, and naps or the following night's sleep destroy it. Various methods have
      been tried to stabilize the positive sleep-deprivation effect. A consecutive 1
      week advance in the sleep phase stabilized mood in more than 50% of the sleep
      deprivation responders. We examined 40 male patients with major depression who in
      addition to medical treatment took part in a phase advance study to prove
      possible synergistic effects. About 60% of the patients showed positive mood
      stabilization after 1-week of treatment when the patients were sleep-deprivation
      responders. These results support data from other groups.

PMID- 9522336
TI  - [Benefits and risks of electroconvulsive therapy (ECG) in elderly patients with
      cardiovascular risk factors].
AB  - Between January 1995 and June 1996, 24 inpatients at our hospital (mean age 55.6
      years) were treated with electroconvulsive therapy (ECT). Clinical improvement
      was observed in 80% of the patients, including those without risk factors (NRG, n
      = 16), as well as those with concomitant cardiovascular diseases (RG, n = 8).
      During a mean period of observation of 224 days after the end of ECT 7 patients
      (35%) relapsed. The rate of relapse was higher in RG than in NRG patients (57.1
      vs 23.1%). In all cases ECT was well tolerated; 285 applications of ECT did not
      result in mortality or persistent morbidity. However, RG patients may be at
      increased risk for the development of minor cardiovascular complications, which
      were noted in three RG patients (37.5%), but only in one patient (6.2%) in the
      NRG (Fisher's test, P = 0.09). Taken together, our results demonstrate that ECT
      is a safe treatment regimen for depression even in medically ill patients of old
      age.

PMID- 9522337
TI  - [Unmasking pheochromocytoma by amitriptyline].
AB  - A report is given about a 57-year-old woman with a major depression, melancholic
      subtype. While under amitriptyline 75 mg/day no adverse effects were observed,
      immediately after increasing the dosage to 150 mg/day "head spasms" with
      headache, profuse sweating and arterial hypertension appeared. The diagnosis of a
      pheochromcytoma was made and adrenalectomy was performed. This is the first case
      of unmasking a pheochromcytoma by amitriptyline; furthermore a connexion was
      found with the daily dosage of the antidepressant.

PMID- 9522338
TI  - [Ethical implications of psychotherapy].

PMID- 9522339
TI  - ["The psychiatric illness of Vincent van Gogh". Comment on the contribution by W.
      K. Strik].

PMID- 9522340
TI  - [An unusual case of psychosis. Scopolamine poisoning with paranoid hallucinatory
      psychosis? Comment on the contribution by O. Rubner, P. W. Kummerhoff, H. Haase].

PMID- 9522342
TI  - [Comments on the position paper of the DGPPN (German Society of Psychiatry,
      Psychotherapy and Neurology].

PMID- 9522341
TI  - [Primary and secondary negative symptoms: still a reliable differentiation?
      Comment on the contribution by W. Barnett. Ch. Mundt, P. Richter].

PMID- 9522344
TI  - Neurovascular flow simulation review.
AB  - Computer simulation of the cerebral circulation has been carried out for three
      decades. We review the developments of cerebral circulation computer models of
      the last 30 years. Existing models are discussed in terms of fluid dynamics and
      possible clinical usage. Also the status and new achievements in some related
      research areas are summarized. Any new achievements in such areas would
      contribute to the progress of building a better model. A patient specific, highly
      predictive and reflective model could be a powerful clinical tool which would
      greatly benefit neurosurgeons and patients.

PMID- 9522343
TI  - Nonlinear analysis of EEG in septic encephalopathy.
AB  - Electroencephalograms (EEG) were recorded in fourteen patients who experienced a
      severe septic encephalopathy (SE). EEG analysis included visual inspection,
      spectral analysis and a recently developed nonlinear analysis (the Kaplan test).
      All EEGs showed decreased fast activity and an increase of slow wave activity on
      visual inspection. There was a nonsignificant trend of negative correlation
      between the spectral EEG analysis and the severity of the acute systemic illness
      (based on the sum score of 14 variables known as APACHE II score) (standard
      coefficient = -0.43, p = 0.118). However, a much more pronounced and significant
      negative correlation was observed between the Kaplan test and the APACHE II score
      (standard coefficient = -0.94, p = 0.005). The EEG abnormalities seen in these
      patients were independent of the sedation level. Neither the EEG parameters, nor
      the APACHE II score, predicted outcome. Nonlinear analysis is more powerful than
      spectral analysis to extract clinical relevant information from EEGs in patients
      who experience a severe SE. The nonlinear EEG analysis suggest that brain
      dynamics in SE may be characterized by a shift into a fundamentally different
      level of cortical information exchange which can be summarized in nonlinear
      terminology as a loss of deterministic structure in the EEG.

PMID- 9522345
TI  - Distribution of nerve growth factor in cat brains following topical application
      of solution or Minipellet.
AB  - The distribution of nerve growth factor (NGF) was studied after topical
      application of NGF solution or NGF Minipellet into the caudate nucleus of cat
      brains. Each aliquot of NGF solution or a piece of NGF Minipellet contains 200
      micrograms of mouse 2.5S beta-NGF. The concentrations of NGF in various areas of
      the brain were determined by enzyme-linked immunosolvent assay (ELISA). The
      tissue concentrations of NGF were very high at 6 h after injection of NGF
      solution (124.0 +/- 2.46 to 2144.0 +/- 16.03 ng g-1), but quickly decreased on
      day 1. The tissue concentrations of NGF were low at 6 h after implantation of NGF
      Minipellet, but were considerably increased on day 1 (11.22 +/- 3.36 to 72.04 +/-
      20.45 ng g-1), and slowly decreased during the following 6 to 14 days. The
      present study demonstrates the temporal and spatial profiles of NGF distribution
      in the brain of middle-sized animals after topical application. Injection of NGF
      solution resulted in abrupt, but very transient, elevation of tissue NGF.
      Implantation of NGF Minipellet maintained the tissue NGF at biologically
      effective levels for 6 to 14 days.

PMID- 9522346
TI  - Argyrophilic structures stimulate glial reactions in neurofibrillary tangles and
      senile plaques.
AB  - Neurofibrillary tangles (NFT) and senile plaques (SP) contain various
      pathological structures, and the majority of these pathological structures are
      argyrophilic. To investigate the glial reactions of the argyrophilic substance,
      we performed immunohistochemistry for microglia or for astroglia after Gallyas
      Braak staining, which is one of the most sensitive silver impregnation techniques
      detecting argyrophilic structures in NFT and SP. We found that extracellular
      argyrophilic structures in NFT and SP showed glial reactions, and we observed
      reactive microglia in the center of NFT and SP in contrast to astroglia, which
      were situated in the periphery. These findings suggest that the exposed
      argyrophilic components in the extracellular space stimulate both glial
      reactions, but that there is a striking difference in localization between
      microglia and astroglia.

PMID- 9522347
TI  - Evidence for apoptosis in human intracranial aneurysms.
AB  - There is no accepted hypothesis explaining the mechanism of growth and the
      subsequent rupture of intracranial aneurysms. Both congenital and acquired
      factors are believed to contribute to the formation and development of
      intracranial aneurysms. Apoptosis, commonly observed under a wide range of
      physiological conditions, occurs in the various pathological situations including
      some vascular diseases. We discuss the contribution of apoptosis to the formation
      and the rupture of human intracranial aneurysm. Five aneurysms without surgical
      treatment from four autopsy cases suffering from subarachnoid hemorrhage were
      studied by a specific in situ nick-end labeling method for DNA breaks.
      Conventional hematoxylin and eosin staining, and van Gieson staining for elastic
      fiber were also performed. Nonatherosclerotic regions in the parent arteries of
      the aneurysms or contralateral arteries were examined for controls in the same
      manner. Many apoptotic cells with nuclear DNA fragmentation were recognized in
      neck and dome of aneurysms, while few findings for DNA breaks were available in
      control arteries. Evidence for apoptosis was present in the spindle-shaped cells
      constituting the thin wall close to the rupture point within aneurysmal dome.
      These results strongly suggest that apoptosis plays an important role not only in
      the development of intracranial aneurysms but also in the aneurysmal rupture.

PMID- 9522348
TI  - Chloride influx during cerebral energy deprivation.
AB  - The purpose of the present study was to investigate the possible role of chloride
      influx and GABA release during cerebral energy deprivation (ED). The functional
      activity measured by evoked activity (population spike) in hippocampal slices was
      recorded during nine minutes of ED and 60 minutes recovery. Treatment groups were
      exposed to ED following administration of the GABAA antagonist penicillin G (pc
      G) or substitution of extracellular chloride. The release of glutamate and GABA
      was measured by HPLC. The efflux of 36Cl from preloaded slices was measured
      during ED with and without blocking the GABAA receptor. The population spike
      disappeared during ED, and there was a marked release of GABA and glutamate.
      During recovery the population spike recovered partially. Both application of pc
      G and substitution of extracellular chloride during ED improved population spike
      recovery. Uptake of radiolabeled chloride was significantly reduced by pc G.
      Glutamate release, but not GABA, was significantly reduced by chloride
      substitution. These results indicate a possible role of chloride mediated injury
      during ED, and suggest that chloride entry may partly occur through ligand
      operated channels. Furthermore there may be an early chloride dependent release
      of glutamate during cerebral ischemia, whereas later release seems to be chloride
      independent.

PMID- 9522349
TI  - Transcranial cerebral oximetry in random normal subjects.
AB  - Near infrared optical spectroscopy is becoming a useful method for monitoring
      regional cerebral oxygenation status. The method is simple, reliable and
      noninvasive and the information which it provides is clinically significant in
      managing a growing number of neurological ailments. Use of this technique has
      been described previously by numerous authors. In the present study, regional
      cerebral oxygen saturation was measured at rest in 94 subjects randomly selected
      from a diverse population of individuals. This sample consisted of 38 males and
      65 females (age range 18-70 years). There were 68 light-skinned individuals and
      35 with darker skin comprising various ethnic and cultural backgrounds. Mean
      regional cerebral hemoglobin oxygen saturation was recorded as 67.14 +/- 8.84%.
      The association of the man regional cerebral hemoglobin oxygen saturation in
      various groups of individuals with relationship to their age, race, sex and skin
      color is examined.

PMID- 9522350
TI  - Intraoperative on-line monitoring of cerebral pH by microdialysis in
      neurosurgical procedures.
AB  - The objective of this study was to improve the ability to detect cerebrovascular
      complications in patients undergoing complicated neurosurgical procedures using
      on-line monitoring of cerebral pH with in vivo microdialysis. We employed on-line
      pH monitoring in patients with a variety of neurosurgical procedures including
      high-flow bypass surgery, aneurysm clipping, and temporal resection in epilepsy
      treatment. The pH was monitored with a microdialysis probe, usually inserted into
      the frontal cortex and pH of the dialysate was measured on-line with a pH
      electrode. We monitored 17 cases: 12 high-flow extracranial-intracranial (EC-IC)
      bypass procedures, 3 surgeries to clip large basilar tip aneurysms under
      protection of hypothermic circulatory arrest, and 2 surgeries for intractable
      seizure disorders. In the patients undergoing high-flow bypass, the pH remained
      stable in 5 patients and all had an uneventful outcome. In 3 patients, the pH
      decreased during surgery. One patient had a severe hemiparesis on awaking from
      anesthesia. The fall in pH in another patient was corrected when the blood
      pressure was raised during surgery. The pH was also responsive to changes in
      intraoperative ventilation and probably also to brain edema with elevation of pH
      values. In the three patients undergoing basilar tip aneurysm clipping under
      hypothermic circulatory arrest, the pH fell to 6.41 in one patient. This patient
      awoke with a mild hemiparesis. In the other two patients, the pH was stable
      during the hypothermia and neither patient had complications. In the patients
      undergoing temporal lobectomy and hippocampectomy, the pH fell rapidly with the
      onset of ischemia. We conclude that it is possible to monitor the cerebral
      extracellular pH with on-line microdialysis. The information obtained may alert
      the surgeon to the possibility of impending cerebral ischemia or other
      complications. However, further experience is needed before the technique can be
      recommended for general use.

PMID- 9522351
TI  - Serial neuroimaging studies in Sotos syndrome (cerebral gigantism syndrome).
AB  - To elucidate the mechanism of excessive size of the head in Soto syndrome, serial
      neuroimaging features from birth were reviewed in two patients. Macrocephaly
      shortly after birth was attributed to increased volume of the cerebral parenchyma
      itself (megalencephalon). Subsequent excessive size of the head was related to
      retention of cerebrospinal fluid in the ventricles and the subarachnoid spaces.
      Thus, macrocephaly in Sotos syndrome reflects two different mechanisms. The value
      of serial evaluation of intracranial structures is emphasized.

PMID- 9522352
TI  - Cost-efficient localization of seizures of mesiotemporal onset with foramen-ovale
      electrodes.
AB  - Foramen ovale (FO) electrodes can identify mesiotemporal lobe (MTL) seizure
      onsets but are infrequently used in the USA. Ten patients with presumed MTL ictal
      onset, unlocalized noninvasively, had FO electrodes inserted during long term
      monitoring for epilepsy. Placement was facilitated by intraoperative use of
      oblique submental and modified Caldwell view fluoroscopy. Eighty percent of
      patients had ictal localization by FO electrodes. This led to anterior temporal
      lobectomy in six with 83% being seizure free after follow-up of 20-32 months. The
      mean total costs of placing these electrodes was approximately half that of
      subdural strips and a quarter that of depth electrodes. Foramen ovale electrodes
      represent a cost-effective and efficient method of seizure localization when
      noninvasive workup suggests but is not definitive for MTL origin.

PMID- 9522353
TI  - Glycine receptor reduction within segmental gray matter in a rat model in
      neuropathic pain.
AB  - Glycine is an amino acid neurotransmitter found in the spinal cord and is closely
      associated with interneurons that modulate afferent activity. We have previously
      shown that low segmental glycine concentrations or blockade of normal glycinergic
      activity lowers the threshold for pain thresholds. In addition, intrathecal
      glycine infusion increases the pain threshold in animal models of neuropathic
      pain. However, the role of the glycine receptor in neuropathic pain is not clear
      and is the basis for the current study. Using a unilateral sciatic nerve
      constriction injury model of neuropathic pain, the strychnine sensitive glycine
      receptor population was studied using immunohistochemical techniques. Glycine
      receptors are reduced in number in the dorsal horn bilaterally in injured
      animals. Glycine and related compounds are potentially valuable agents for
      treating chronic pain conditions in humans. A better understanding of glycine
      receptor interactions should prove valuable as these compounds are studied in
      greater depth.

PMID- 9522354
TI  - Pathways of cerebral calcium accumulation in a model of focal ischemia in rats.
AB  - Focal cerebral ischemia was produced in anesthetized rats by a minimally invasive
      photothrombic procedure. Rose bengal was injected into a tail vein and the right
      middle cerebral artery region irradiated for 5 min through the skull with the
      right common carotid artery temporarily occluded. This resulted in focal cerebral
      infarction which was restricted to the cortex as shown by autoradiography and
      histopathology. Edema and the uptake of 45Ca were determined 1, 3 or 24 hours
      after ischemia in different regions of the brain, ipsilateral and contralateral
      to the ischemic injury, the tracer uptake at three time points after
      administration. The values of 45Ca uptake and edema were the highest at the
      center of the infarction. Simulation of the 45Ca uptake kinetics in the 24 h post
      ischemic group, enabled the determination of the contributions of different
      physiological pathways to cerebral calcium flux. The results indicated the
      breakdown of the blood-brain barrier to be primarily responsible for the
      increased uptake of the tracer by the ischemic cortex. A concomitant, presumably
      intracellular, sequestration resulted in a ca. 16-fold increase in the tissue
      pool of exchangeable calcium. Simulation such as proposed here would be of value
      in predicting the outcome of tracer accumulation in pathological situations.

PMID- 9522355
TI  - Fosphenytoin.
AB  - Fosphenytoin is a phenytoin prodrug that has been introduced to overcome some of
      the problems and limitations associated with parenteral phenytoin sodium
      administration. Fosphenytoin is a phosphate ester prodrug that is converted to
      phenytoin in vivo by peripheral esterases. Fosphenytoin has several advantages
      and disadvantages that should be considered when selecting its use in place of
      parenteral phenytoin. Advantages with fosphenytoin include better tolerability,
      improved safety, better stability, ability for intramuscular administration, and
      faster infusion rates. Disadvantages with fosphenytoin include rate and dose
      related paresthesias and pruritus, delayed decreases in blood pressure, the
      potential for therapeutic drug monitoring errors, and higher drug acquisition
      costs. In general, given the pros and cons of the new drug, fosphenytoin offers
      an attractive alternative for parenteral phenytoin in select individuals.

PMID- 9522356
TI  - Short-term and long-term excitability changes of the insular cortical neurons
      after the acquisition of taste aversion learning in behaving rats.
AB  - Conditioned taste aversion, a long-lasting type of learning established after a
      single pairing of a novel taste and subsequent internal malaise, is an adaptive
      behavior to prevent animals from repeated intakes of poisonous substances. The
      present study was designed to identify the time-dependent excitability changes of
      cortical neurons to gustatory stimuli after the acquisition of conditioned taste
      aversion in freely behaving rats. Conditioned taste aversion to saccharin was
      established by an intraperitoneal injection of lithium chloride, a sickness
      inducing agent, soon after an intraoral infusion of saccharin. Twenty minutes
      after the pairing, 25 (29%) of 86 rats showed aversive taste reactivities to
      saccharin, and 30 min after the pairing, all of the rats showed aversive
      behaviors to saccharin; these behavioral changes lasted throughout the test
      session (over 360 min). When unit activities were recorded from the insular
      cortex simultaneously with the behavioral test, 14 (11%) of 122 neurons showed a
      significant enhancement of excitability in response to saccharin, but not to
      other taste stimuli, after the acquisition of taste aversion. Eight of these 14
      neurons showed a short-term enhancement: significant effects were detected only
      30 min after the pairing. The remaining six neurons exhibited a long-term
      enhancement: the effects lasted over 360 min after the pairing. The existence of
      such short-term and long-term excitability changes suggests that the gustatory
      insular cortex is involved in different aspects of taste aversion learning.

PMID- 9522357
TI  - Nuclear estrogen receptor-independent neuroprotection by estratrienes: a novel
      interaction with glutathione.
AB  - Post-menopausal estrogen replacement therapy is associated with a reduction in
      the risk of Alzheimer's disease and has been reported to improve cognitive
      functioning in several small clinical trials. The present study evaluates the
      dependence of estrogenic neuroprotection on the presence of estrogen receptors
      using the murine neuronal cell line, HT-22, exposed to the neurotoxic beta
      amyloid peptide. These cells lack functional estrogen receptors. The amyloid
      peptide killed 50-60% of these cells and concurrent treatment with either of
      three estratrienes, beta-estradiol, alpha-estradiol, or estratrien-3-ol, resulted
      in a dose-dependent protection. The potency of this estrogen neuroprotection was
      dependent on the presence of glutathione in the culture media. The presence of
      reduced glutathione in the media increases the neuroprotective potency of
      estrogens by an average of 400-fold. These results demonstrate that a nuclear
      estrogen receptor is not necessary for the neuroprotective actions of estrogens;
      however, the presence of an appropriate antioxidant in the extracellular milieu
      is needed for estratriene neuroprotection at physiologically and
      pharmacologically relevant doses. These data suggest the possibility of combined
      estrogen-antioxidant therapy for neurodegenerative diseases such as Alzheimer's
      disease.

PMID- 9522358
TI  - The contribution of intracortical inhibition to dynamics of orientation tuning in
      cat striate cortex neurons.
AB  - Orientation tuning of some neurons in cat visual cortex (area 17) revealed
      successive shifts of the preferred orientation and widening of tuning in time
      during the first 150 ms after onset of a flashing light bar. The mechanisms of
      these dynamics and the possible role of intracortical inhibition are still under
      discussion. In this study we analysed the dynamics using the time slice method
      before and during blockade of GABAergic inhibition by microiontophoretic
      application of bicuculline and observed two main types of neuronal behaviour. The
      first group of neurons (39 of 68 units or 57.4%) with relatively sharp tuning and
      absence or relatively small shifts of preferred orientation under control
      conditions increased or developed this shift during bicuculline application.
      Changes in tuning were observed between 30 and 150 ms after stimulus onset when
      inhibition was blocked. Neurons of the second group (29 units or 42.6% of cases)
      displayed pronounced shifts of preferred orientation under control conditions
      which was typically diminished or lost during blockade of inhibition. The results
      indicate different contributions of intracortical inhibition to different neurons
      distinguishing by stability or time dependence of their orientation preference
      during normal response generation. In one group of striate cells orientation
      tuning was kept narrow and constant in time by intracortical inhibition, while in
      another group orientation tuning dynamics are induced by inhibitory mechanisms.

PMID- 9522359
TI  - Orientation tuning and receptive field structure in cat striate neurons during
      local blockade of intracortical inhibition.
AB  - The contribution of intracortical inhibition to orientation tuning in the cat
      striate cortex (area 17) was studied by responses to flashing light bars of
      different orientations and lengths in 68 single-units before and during
      microiontophoretical application of bicuculline, a GABAA antagonist, A three-fold
      increase in the background activity (13.3 +/- 1.3 vs 4.4 +/- 0.5 imp/s) and 4.4
      fold increase in the maximal discharge frequency (264.4 +/- 22.3 vs 60.6 +/- 5.3
      imp/s) was found in 96.0% of the cells studied during microiontophoresis. In most
      units all characteristics of orientation tuning significantly changed during
      application of bicuculline: i) tuning width increased in 76.3% of cells from 52.7
      +/- 2.8 degrees in control to 85.2 +/- 4.6 degrees, ii) tuning selectivity
      diminished in 63.6% of cells by a factor of 1.5, and iii) tuning quality dropped
      in 68.5% of cases by a factor of 2.5. The threshold ejection current of
      bicuculline for widening of tuning was in 2/3 of the cells in the range from +10
      to +40 nA (+31.0 +/- 4.5 nA) and the maximum effect was obtained in 3/4 of units
      with +30(-) + 100 nA (+67.1 +/- 6.0 nA). Unmasking of additional excitatory
      inputs to the studied cells due to blockade of the inputs from inhibitory
      interneurons in considered as the main mechanism of the described bicuculline
      effects.

PMID- 9522360
TI  - The K+ channel, Kv2.1, is apposed to astrocytic processes and is associated with
      inhibitory postsynaptic membranes in hippocampal and cortical principal neurons
      and inhibitory interneurons.
AB  - A variety of voltage-gated ion channels are expressed on principal cell dendrites
      and have been proposed to play a pivotal role in the regulation of dendritic
      excitability. Previous studies at the light microscopic level demonstrated that
      the K+ channel subunit Kv2.1 expression was polarized to the cell soma and
      dendrites of principal neurons throughout the central nervous system. Here, using
      double immunostaining we now show that Kv2.1 protein is similarly expressed in
      the majority of cortical and hippocampal parvalbumin, calbindin and somatostatin
      containing inhibitory interneurons. At the electron microscopic level Kv2.1
      immunoreactivity was primarily observed on the plasma membrane of the somata and
      proximal dendrites of both principal neurons and inhibitory interneurons;
      expression was low on smaller dendritic branches, and absent on axons and
      presynaptic terminals. Kv2.1 subunit expression was highly concentrated on the
      cell surface membrane immediately facing astrocytic processes. Kv2.1 expression
      was also concentrated in specific cytoplasmic compartments and on the subsurface
      cisterns underlying the plasma membrane facing astrocytes. In addition, Kv2.1
      subunit immunoreactivity was associated with postsynaptic densities of a fraction
      of inhibitory symmetric synapses; while expression at asymmetric synapses was
      rare. These data demonstrate that channels formed by Kv2.1 subunits are uniquely
      positioned on the soma and principal dendrites of both pyramidal cells and
      inhibitory interneurons at sites immediately adjacent to astrocytic processes.
      This close apposition to astrocytes will ensure a rapid removal and limit the
      influence of K+ released into the extracellular space. This expression pattern
      suggests that channels formed by Kv2.1 are poised to provide a role in the
      regulation of neuronal dendritic excitability.

PMID- 9522361
TI  - Reduction of the extracellular level of glutamate in the median raphe nucleus
      associated with hippocampal theta activity in the anaesthetized rat.
AB  - The relationship between hippocampal activity and the extracellular level of
      excitatory amino acids in the median raphe nucleus has been studied in urethane
      anaesthetized rats, using the in vivo microdialysis technique. Dialysates were
      collected from the median raphe nucleus during two to eight sampling periods of
      equal length (20 min) and hippocampal electroencephalogram was continuously
      monitored. For each observation period, the average glutamate level in the median
      raphe nucleus was determined and the percentage of theta and non-theta segments
      in the hippocampal recordings was calculated. Theta synchronization, in these
      experiments, either developed spontaneously or it was elicited by injection of
      anticholinesterase (Physostigmine or Sintostigmine, i.p.) or by a series of short
      tail pinches. The relationship between hippocampal activity and glutamate release
      in the median raphe nucleus was characterized by comparison of the direction of
      changes in these two parameters in consecutive sampling periods. We found that as
      long as theta/non-theta ratio changed spontaneously or under the effect of
      anticholinesterase (n = 7), the extracellular level of glutamate in the median
      raphe nucleus was elevated during periods dominated by desynchronized hippocampal
      activity as compared with those mostly containing long and/or frequently
      occurring theta segments. Such relationship was not observed in the adjacent
      reticular formation (n = 4) and in the median raphe nucleus during sensory
      stimulation (n = 2). The present data complete those found earlier indicating
      that the desynchronizing serotonergic influence originating from the brainstem is
      maintained by a tonic excitatory input to the median raphe nucleus. Since the
      majority of glutamatergic afferents to the median raphe nucleus originates from
      the lateral habenula and the interpeduncular nucleus, known to connect limbic
      forebrain to the brainstem, theta associated changes in median raphe nucleus
      glutamate levels might reflect descending forebrain influences, suggesting
      therefore a feedback regulation of the hippocampal activity involving brainstem
      structures.

PMID- 9522362
TI  - Adenosine A2 receptors modulate hippocampal synaptic transmission via a cyclic
      AMP-dependent pathway.
AB  - Blockade of adenosine A2 receptors has been shown to significantly reduce the
      level of tetanus-induced long-term potentiation in area CA1 of rat hippocampus
      [Kessey K. et al. (1997) Brain Res. 756, 184-190; Sekino Y. et al. (1991)
      Biochem. biophys. Res. Commun. 181, 1010-1014]. In the present study, the effects
      of A2 receptor activation and blockade on the modulation of normal synaptic
      transmission and tetanus-induced long-term potentiation were examined at the
      Schaffer-CA1 synapse in rat hippocampal slices. A2 receptor activation reversibly
      enhanced synaptic transmission evoked by low-frequency test pulses as measured by
      the dendritic field excitatory postsynaptic potential. In the presence of A1
      receptor blockade, A2 activation further enhanced the excitatory postsynaptic
      potential, while A2 receptor blockade resulted in a reversible decrease of the
      excitatory postsynaptic potential. The A2a receptor agonist, CGS21680, had no
      effect on the excitatory postsynaptic potential, suggesting that tonic activation
      of A2b receptors contributes to synaptic transmission under normal physiological
      conditions. Furthermore, we investigated the contribution of A2 receptors to the
      level of tetanus-induced long-term potentiation. Under control conditions, a
      single tetanus potentiated the excitatory postsynaptic potential by 63.5%
      relative to baseline 30 min post-tetanus. In contrast, tetanus-induced long-term
      potentiation during A2 blockade was 21.3%. A2 receptor activation increased the
      level of tetanus-induced long-term potentiation to 90.2%. Because A2 receptors
      are known to stimulate cyclic-AMP accumulation, the possible involvement of
      cyclic-AMP was examined. Forskolin, a direct adenylate cyclase activator, and 8
      bromo-cyclic-AMP, a membrane-permeable analog of cyclic-AMP, were able to
      reconstitute tetanus-induced long-term potentiation during A2 receptor blockade;
      however, the inactive analog 1,9-dideoxyforskolin had no effect, indicating that
      the effects of A2 activation on synaptic transmission were mediated largely
      through the regulation of intracellular cyclic-AMP. Because A1 receptors exert an
      opposing effect on synaptic transmission relative to A2 receptors, these results
      suggest that the stoichiometry of A1 versus A2 receptor activation appears to
      play an important role in the modulation of normal synaptic transmission and long
      term potentiation in the CA1 region of the hippocampus.

PMID- 9522364
TI  - Induction of protein inhibitor of neuronal nitric oxide synthase/cytoplasmic
      dynein light chain following cerebral ischemia.
AB  - Administration of inhibitors of neuronal nitric oxide synthase or deletion of the
      encoding gene in rodents provided evidence that neuronal nitric oxide synthase
      activity may contribute to neuronal cell death following global and focal
      cerebral ischemia. In the present study, we investigated by in situ hybridization
      the expression of an endogenous inhibitor of neuronal nitric oxide synthase
      activity, designated protein inhibitor of neuronal nitric oxide synthase and
      homologous to cytoplasmic dynein light chain, in the post-ischemic rat brain.
      Following global ischemia induced by cardiac arrest, messenger RNA expression of
      protein inhibitor of neuronal nitric oxide synthase was rapidly induced in
      pyramidal neurons of the hippocampal CA3 region and granule cell of the dentate
      gyrus which are resistant to ischemic damage. In vulnerable CA1 pyramidal neurons
      however, protein inhibitor of neuronal nitric oxide synthase expression remained
      at basal level after global ischemia and was associated with an increase in
      nicotinamide adenine dinucleotide phosphate-diaphorase activity and subsequent
      DNA fragmentation indicating ischemia-mediated neuronal cell death. Following
      focal cerebral ischemia induced by permanent occlusion of the middle cerebral
      artery, transcripts of protein inhibitor of neuronal nitric oxide synthase
      progressively accumulated in cortical neurons bordering the infarct area. After
      transient middle cerebral artery occlusion however, messenger RNA levels of
      protein inhibitor of neuronal nitric oxide synthase increased in the reperfused
      neocortex. Our findings indicate that cerebral ischemia leads to an increase in
      neuronal expression of protein inhibitor of neuronal nitric oxide synthase in
      brain regions where sustained or "uncoupled" nitric oxide synthase activity may
      be detrimental to neurons. Lack of post-ischemic induction of protein inhibitor
      of neuronal nitric oxide synthase in CA1 pyramidal neurons may result in high
      nitric oxide synthase activity after global ischemia and could contribute to
      delayed neuronal cell death.

PMID- 9522363
TI  - The pro-convulsant actions of corticotropin-releasing hormone in the hippocampus
      of infant rats.
AB  - Whole-cell patch-clamp and extracellular field recordings were obtained from 450
      microns-thick brain slices of infant rats (10-13 days postnatal) to determine the
      actions of corticotropin-releasing hormone on glutamate- and GABA-mediated
      synaptic transmission in the hippocampus. Synthetic corticotropin-releasing
      hormone (0.15 microM) reversibly increased the excitability of hippocampal
      pyramidal cells, as determined by the increase in the amplitude of the CA1
      population spikes evoked by stimulation of the Schaffer collateral pathway. This
      increase in population spike amplitude could be prevented by the corticotropin
      releasing hormone receptor antagonist alpha-helical (9-41)-corticotropin
      releasing hormone (10 microM). Whole-cell patch-clamp recordings revealed that,
      in the presence of blockers of fast excitatory and inhibitory synaptic
      transmission, corticotropin-releasing hormone caused only a small (1-2 mV)
      depolarization of the resting membrane potential in CA3 pyramidal cells, and it
      did not significantly alter the input resistance. However, corticotropin
      releasing hormone, in addition to decreasing the slow afterhyperpolarization,
      caused an increase in the number of action potentials per burst evoked by
      depolarizing current pulses. Corticotropin-releasing hormone did not
      significantly change the frequency, amplitude or kinetics of miniature excitatory
      postsynaptic currents. However, it increased the frequency of the spontaneous
      excitatory postsynaptic currents in CA3 pyramidal cells, without altering their
      amplitude and single exponential rise and decay time constants. Corticotropin
      releasing hormone did not change the amplitude of the pharmacologically isolated
      (i.e. recorded in the presence of GABAA receptor antagonist bicuculline)
      excitatory postsynaptic currents in CA3 and CA1 pyramidal cells evoked by
      stimulation of the mossy fibers and the Schaffer collaterals, respectively.
      Current-clamp recordings in bicuculline-containing medium showed that, in the
      presence of corticotropin-releasing hormone, mossy fiber stimulation leads to
      large, synchronized, polysynaptically-evoked bursts of action potentials in CA3
      pyramidal cells. In addition, the peptide caused a small, reversible decrease in
      the amplitude of the pharmacologically isolated (i.e. recorded in the presence of
      glutamate receptor antagonists) evoked inhibitory postsynaptic currents in CA3
      pyramidal cells, but it did not significantly alter the frequency, amplitude,
      rise and decay time constants of spontaneous or miniature inhibitory postsynaptic
      currents. These data demonstrate that corticotropin-releasing hormone, an
      endogenous neuropeptide whose intracerebroventricular infusion results in seizure
      activity in immature rats, has diverse effects in the hippocampus which may
      contribute to epileptogenesis. It is proposed that the net effect of
      corticotropin-releasing hormone is a preferential amplification of those incoming
      excitatory signals which are strong enough to reach firing threshold in at least
      a subpopulation of CA3 cells. These findings suggest that the actions of
      corticotropin-releasing hormone on neuronal excitability in the immature
      hippocampus may play a role in human developmental epilepsies.

PMID- 9522365
TI  - Insulin-like growth factor-I analogue prevents apoptosis mediated through an
      interleukin-1 beta converting enzyme (caspase-1)-like protease of cerebellar
      external granular layer neurons: developmental stage-specific mechanisms of
      neuronal cell death.
AB  - Using an organotypic slice culture system of neonatal rat cerebellum, we examined
      developmental stage-specific mechanisms of cell death of granule neurons. This
      culture system allows a serial process of granule neuron development including
      their proliferation during the early culture period and the proceeding migration
      from the external granular layer to the internal granular layer in the presence
      of a supraphysiological concentration (5 micrograms/ml) of insulin. Insulin
      deprivation induced apoptosis of granule neurons in external granular layer but
      not in internal granular layer. A truncated analogue of insulin-like growth
      factor-I (des (1-3) insulin-like growth factor-I) prevented this apoptosis at a
      concentration of 65-650 ng/ml. Some apoptotic granule neurons expressed
      proliferating cell nuclear antigen but not TAG-1, a marker protein of the
      postmitotic and premigratory granule neurons. Thus, this apoptosis occurred at a
      specific stage in granule neuron development: at the stage before TAG-1
      expression and at least partly at the proliferative state. Ac-YVAD-CHO, an
      inhibitor of interleukin-1 beta converting enzyme (caspase-1)-like proteases, had
      a protective effect on this apoptosis. Interleukin-1 beta converting enzyme
      (caspase-1)-like protease activity increased under the apoptosis-induced
      condition. High concentration of K+, which is known to prevent granule neuron
      apoptosis in dissociated cultures, had a partial protective effect on this
      apoptosis. These findings suggest that (i) cerebellar granule neurons fall into
      apoptosis at the specific developmental stage unless stimulated by insulin-like
      growth factor-I (analogue), (ii) this apoptosis is mediated through an
      interleukin-1 beta converting enzyme-like protease, and (iii) this apoptosis
      consists of K(+)-sensitive and K(+)-insensitive components.

PMID- 9522366
TI  - Distribution of the neurotrophins brain-derived neurotrophic factor, neurotrophin
      3, and neurotrophin-4/5 in the postnatal rat brain: an immunocytochemical study.
AB  - The neurotrophin family of trophic factors influences survival and function of
      neurons in both the peripheral and central nervous systems. Critical information
      regarding physiological function of these factors may be gained by examining
      their localization in the brain. Here we report the immunocytochemical
      characterization of antisera directed against brain-derived neurotrophic factor,
      neurotrophin-3, and neurotrophin 4/5. These antisera provide important tools to
      localize the bioactive neurotrophin proteins. Correspondence between protein
      distribution and previously determined messenger RNA expression was observed in
      some brain regions, such as hippocampus and cortex. However, neurotrophin
      proteins were also detected in neurons which have no apparent corresponding
      messenger RNA, indicating that the proteins may be transported from the sites of
      synthesis in certain populations. Immunocytochemical double-labelling analysis
      also indicated that a sub-population of neurotrophin-positive cells were labelled
      with an astrocyte marker (glial fibrillary acidic protein) as well, demonstrating
      that trophic molecules are localized to glial cells as well as neurons in vivo.
      Thus, the use of antisera specific for individual neurotrophic factors has
      indicated potential cellular sites of action.

PMID- 9522367
TI  - Simultaneous expression of brain-derived neurotrophic factor and neurotrophin-3
      in Cajal-Retzius, subplate and ventricular progenitor cells during early
      development stages of the rat cerebral cortex.
AB  - To identify production sites and action targets of neurotrophins during
      neurogenesis, we investigated immunoreactivities of neurotrophins and their
      tyrosine kinase receptors in the cerebral cortex of rat embryos. Two sets of
      ligand-receptor systems, brain-derived neurotrophic factor/TrkB and neurotrophin
      3/TrkC, were expressed simultaneously in Cajal-Retzius, subplate neurons and
      ventricular multipotent stem cells at embryonic days 13 and 15. Intraventricular
      administration of brain-derived neurotrophic factor or neurotrophin-3 at
      embryonic day 16 markedly modulated microtubule-associated protein II and/or Hu
      protein expression in different ways in the cortical plate cells by embryonic day
      20. These observations indicate the involvement of autocrine and/or local
      paracrine action of brain-derived neurotrophic factor and/or neurotrophin-3
      during formation of the cerebral cortex.

PMID- 9522368
TI  - Synergistic but transient rescue effects of BDNF and GDNF on axotomized neonatal
      motoneurons.
AB  - Brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic
      factor (GDNF), members of distinct families of polypeptide growth factors, have
      been shown to support motoneurons under various in vitro and in vivo conditions.
      We used a model of motoneuron cell death induced by sciatic nerve section in
      newborn rats and compared the efficacy of BDNF and GDNF administered alone or
      simultaneously in order to determine whether combinations of neurotrophic
      proteins can produce more potent motoneuron rescue than individual factors. The
      factors were administered by different methods, including (i) a single dose on to
      the transected nerve, (ii) continuous delivery from implanted slow-release
      polymer rods (BDNF) or encapsulated cells (GDNF), and (iii) repeated systemic
      injections (BDNF). Irrespective of the method of administration, either factor
      alone produced rescue effects which dramatically declined at two weeks as
      compared to one week post-lesion. In contrast, this decrease was significantly
      reduced when BDNF and GDNF were used simultaneously provided that one factor was
      applied on to the nerve while the other was continuously released from the rods
      or capsules. Other combinations in which GDNF was replaced by ciliary
      neurotrophic factor or axokine-1 failed to reproduce such additive activity. Two
      conclusions can be made from these experiments. First, when BDNF and GDNF are
      administered simultaneously but by distinct routes of delivery, their survival
      promoting effects on the injured developing motoneurons are potentiated; second,
      even continuous delivery of each of these trophic factors alone cannot completely
      abrogate the time-dependent decline in rescue effects in this model of motoneuron
      cell death.

PMID- 9522369
TI  - Motoneuron survival and expression of neuropeptides and neurotrophic factor
      receptors following axotomy in adult and ageing rats.
AB  - Three months after facial nerve transection, total numbers of motoneurons in the
      facial nucleus of six month (adult) Fischer 344 and Wistar rats were reduced to
      83% and 75% of contralateral values, respectively (P < 0.05). This procedure in
      22-26 month (ageing) Fischer 344 rats and Wistar rats resulted in a reduction of
      motoneuron numbers to 77% and 60% of the respective contralateral values (P <
      0.05). Compared to adults, contralateral facial nuclei of aging Fischer 344 rats
      contained 10% fewer motoneurons (non-significant), while ageing Wistar rats had
      22% fewer (P < 0.05). No significant changes were found in the proportion of
      surviving motoneurons expressing calcitonin gene-related peptide, galanin,
      receptor tyrosine kinase-C or the alpha subunit of the ciliary neurotrophic
      factor receptor. We conclude that ageing reduces facial motoneuron number and
      increases their vulnerability to axotomy in Wistar rats, but not in Fischer 344
      rats. In neither strain, however, does the proportion of surviving motoneurons
      expressing the above neuropeptides or neurotrophic factor receptors change. This
      information may be relevant to those hypotheses of age-related neuronal
      degenerations which assume that decreased neurotrophic support renders ageing
      neurons more vulnerable to injury.

PMID- 9522370
TI  - Enlargement of motoneuron peripheral field following partial denervation with or
      without dorsal rhizotomy.
AB  - In partially denervated skeletal muscle, spared motor fibres sprout, enlarging
      motor unit size. Neuritogenesis and sprouting are known to depend on the synaptic
      input to the neurons. This suggests that spared motoneuron reaction to partial
      muscle denervation might be controlled by primary sensory neurons which directly
      or indirectly project to motoneurons. In two groups of rats, different surgical
      procedures were carried out: partial denervation of the extensor digitorum longus
      muscle without or with homolateral dorsal rhizotomy. Spared motoneuron peripheral
      field was evaluated by nerve-evoked tension measures. Following partial muscle
      denervation, spared motoneurons enlarged their projection peripheral field five
      to six times, innervating most of the denervated portion of the muscle. When
      dorsal rhizotomy was carried out together with partial denervation, the
      enlargement of the motoneuron's peripheral field occurred later; however, the
      peripheral field size was the same or greater than that found in partially
      denervated muscles without dorsal rhizotomy in the long term. Excitatory
      postsynaptic potential recordings at neuromuscular junctions consistently showed
      that innervation of denervated muscle cells by spared motoneurons was impaired
      when the dorsal roots were cut. Finally, in both groups of operated rats an
      increase in motor unit number occurred early after surgery, anticipating a
      process normally occurring in the same age range. These findings are consistent
      with the idea that sensory input trans-synaptically controls motoneuron
      peripheral field size.

PMID- 9522371
TI  - Expression of Jun, Fos, and ATF-2 proteins in axotomized explanted and cultured
      adult rat dorsal root ganglia.
AB  - The expression of c-Jun, JunB, JunD, c-Fos and ATF-2 transcription factors was
      studied in L4/L5 dorsal root ganglion neurons of adult rats, in order to
      determine the extent to know to which extend the expression of transcription
      factors in vitro parallels the pathophysiological expression in vivo. First,
      dorsal root ganglia were dissociated and cultured for up to 15 days in vitro
      (culture). Second, the dorsal root and the peripheral nerve fibres were
      transected close at the dorsal root ganglia, and the completely axotomized dorsal
      root ganglia were kept in artificial cerebrospinal fluid for up to 24 h. This
      procedure (explantation) preserves the intraganglionic morphology intact. Culture
      evoked a persistent expression of c-Jun and JunD in the majority of small neurons
      independent on neurite extension, In contrast, the number of large neurons with c
      Jun decreased and with JunD increased with incubation time. JunB and c-Fos, which
      were also visible in the majority of neurons, strongly decreased with culture
      time in both small and large neurons. ATF-2 was visible in the vast majority of
      neurons and did not change during the observation period. Incubation with brain
      derived neurotrophic factor for 15 days reduced JunB expression and raised c-Fos
      expression, but did not affect c-Jun or JunD labelings. Explantation of dorsal
      root ganglia evoked a dramatic and rapid induction of c-Jun in neurons located in
      the periphery of the ganglia, an area that showed prominent apoptosis as
      visualized by transferase dUTP nick end-labelling, followed by a delayed increase
      in neurons of the central parts of dorsal root ganglia. Expression of JunB showed
      a dramatic increase within 2 h in the whole ganglion, but disappeared within the
      following hours. JunD dropped from its basal levels within 4 h and was almost
      absent after 8 h. c-Fos did not appear until 6 h, when transferase dUTP nick end
      labelling also became detectable, and remained visible in a rather small number
      of neurons. As with culture, incubation of explanted dorsal root ganglia with
      brain-derived neurotrophic factor prevented the initial rise in JunB, accelerated
      and enhanced c-Fos expression, but did not alter c-Jun and JunD expression.
      Immunoreactivity of ATF-2 declined or disappeared in those dorsal root ganglia
      compartments that showed a rise in c-Jun and transferase dUTP nick end-labelling.
      These findings demonstrate that inducible transcription factors such as Jun and
      Fos proteins are differentially expressed in adult neurons in vitro when compared
      to pathophysiological conditions in vivo such as nerve fibre transection (axotomy
      or rhizotomy). Moreover, the comparison between the explantation and culture
      experiments suggests that it is the complete axotomy of neurons that provokes
      those expression patterns found in neuronal cultures of adult neurons. The rapid
      and persisting expression of c-Jun during neurite extension and apoptosis points
      at the activation of a pivotal program that might be determined by the presence
      or absence of ATF-2 and that is involved in regeneration or degeneration.

PMID- 9522372
TI  - Semi-quantitative ultrastructural analysis of the localization and neuropeptide
      content of gonadotropin releasing hormone nerve terminals in the median eminence
      throughout the estrous cycle of the rat.
AB  - The ultrastructural appearance of gonadotropin releasing hormone-immunoreactive
      elements was studied in the external zone of the median eminence of adult female
      Wistar rats. On the one hand, the purpose of the study was to determine the
      distribution of gonadotropin releasing hormone terminals towards the
      parenchymatous basal lamina at the level of hypothalamo-hypophyseal portal
      vessels, throughout the estrous cycle. On the other hand, we have semi-quantified
      the gonadotropin releasing hormone content in nerve terminals or preterminals
      during this physiological condition. A morphometric study was coupled to a
      colloidal 15 mn gold postembedding immunocytochemistry procedure. Animals were
      killed at 09.00 on diestrus II, 0.900, 10.00, 13.00, 17.00 and 18.00 on proestrus
      and 09.00 on estrus (n = 4-8 rats/group). A preliminary light microscopic study
      was carried out to identify an antero-posterior part of median eminence strongly
      immunostained by anti-gonadotropin releasing hormone antibodies but which was, in
      addition, easily spotted. This last condition was necessary to make a good
      comparison between each animal. Contacts between gonadotropin releasing hormone
      nerve terminals and the basal lamina were observed only the day of proestrus.
      Such contacts, however, were rare and in the great majority of cases,
      gonadotropin releasing hormone terminals are separated from basal lamina by
      tanycytic end feet. The morphometric analysis showed no significant variation in
      average distance between gonadotropin releasing hormone terminals and capillaries
      throughout the estrous cycle. Consequently, it did not appear that a large
      neuroglial plasticity exists during the estrous cycle. However, the observation
      of contacts only on proestrus together with some ultrastructural images evoke the
      possibility of a slight plasticity. The semi-quantitative results show that the
      content of gonadotropin releasing hormone in the nerve endings presented two
      peaks on proestrus: one at 09.00 (23 +/- 5 particles/micrograms2, P < 0.03)
      before the onset of luteinizing hormone surge, and the second at 18.00 (16 +/- 2
      particles/micrograms2, P < 0.01) concomitantly with the luteinizing hormone
      surge, when compared to baseline values on proestrus 10.00 (8 +/-
      particles/micrograms2).

PMID- 9522373
TI  - Stress promotes major changes in dopamine receptor densities within the
      mesoaccumbens and nigrostriatal systems.
AB  - This study investigated the effects of stress on brain dopamine receptor
      densities in two inbred strains of mice. Analysis of [3H]SCH23390 binding by
      quantitative autoradiography revealed that repeated restraint stress
      significantly increases D1-like receptor density in the nucleus accumbens of mice
      of the DBA/2 strain whist reducing it in the caudate-putamen of C57BL/6 mice. No
      significant changes in D2-like receptor quantified by [3H](-)-sulpiride binding
      were observed in caudate, substantia nigra and accumbens of stressed C57BL/6
      mice. Instead, in DBA/2 mice, stress significantly increased D2-like receptor
      density in the nucleus accumbens whilst reducing it in the substantia nigra.
      Finally, stress significantly increased D2-like receptor density within the
      ventral tegmental area of C57BL/6 mice whilst significantly reducing it in mice
      of the DBA/2 strain. These results indicate that stress promotes major changes in
      mesoaccumbens and nigrostriatal dopamine receptor densities. The direction of
      these changes depends on receptor subtype, brain area and strain. Moreover, the
      opposite changes of D2-like receptor densities promoted by stress in the ventral
      tegmental area of the two inbred strains of mice suggest that mesoaccumbens
      dopamine autoreceptors density might be controlled by a major genotype x stress
      interaction.

PMID- 9522374
TI  - Haloperidol induces persistent down-regulation of tyrosine hydroxylase
      immunoreactivity in substantia nigra but not ventral tegmental area in the rat.
AB  - The dopamine antagonist haloperidol can cause tardive side-effects that may
      persist after the drug is withdrawn. We studied the time course of changes in
      dopaminergic neurons of the substantia nigra and ventral tegmental area following
      withdrawal of haloperidol. Rats received daily intraperitoneal injections of
      saline or haloperidol for eight weeks and were killed at two, four or 12 weeks
      after the final injection. Sections of substantia nigra and ventral tegmental
      area were processed for tyrosine hydroxylase immunohistochemistry. Quantitative
      morphometric analysis was carried out blinded in order to determine the number,
      cell body size and topography of tyrosine hydroxylase-positive cells, and the
      immunoreactive area of the substantia nigra and ventral tegmental area. In
      haloperidol-treated rats, tyrosine hydroxylase-positive cell counts were normal
      in ventral tegmental area but were decreased in substantia nigra by 34% at two
      weeks withdrawal and by 52% at four weeks withdrawal; cell counts were almost
      fully recovered by 12 weeks withdrawal. Cross-sectional area of tyrosine
      hydroxylase immunoreactivity within the substantia nigra demonstrated a similar
      pattern of reduction, with full recovery by 12 weeks withdrawal. Mean cell size,
      by contrast, was essentially unchanged at two and four weeks withdrawal, but was
      significantly decreased in sub-regions of substantia nigra at 12 weeks
      withdrawal. These results indicate that haloperidol can produce selective changes
      in midbrain dopamine neurons that persist long after discontinuation of the drug.
      This decrease in tyrosine hydroxylase-immunoreactive cell counts may play a role
      in the neurobiology of the persistent tardive syndromes associated with the use
      of neuroleptics.

PMID- 9522375
TI  - Behavioural recovery after unilateral lesion of the dopaminergic
      mesotelencephalic pathway: effect of repeated testing.
AB  - Functional recovery following a complete unilateral lesion of the nigrostriatal
      pathway in adult rats was studied. We examined the effect of training on the
      spontaneous or induced postural bias following the lesion. Two tasks measuring
      lateralization were used to assess the lesion-induced postural bias: spontaneous
      asymmetry was evaluated in the Y-maze, whereas induced body bias was measured by
      hanging the rat by its tail. Recovery was assessed at three different times
      following the lesion. The effects of lesion in adult rats in the short, medium
      and long term were evaluated and compared with the effects of dopaminergic
      transplants. In adult lesioned rats, destruction of dopaminergic innervation of
      the neostriatum induced initially an ipsilateral bias as measured in the "tail
      hang test" and the Y-maze. Recovery of function was observed in the tail hang
      test as ipsilateral bias declined on repeated testing. Apart from this effect,
      there was a post-lesion interval effect, since the postural bias disappeared more
      rapidly on repeated testing in the long-term lesioned rats. This spontaneous
      recovery was impaired by intrastriatal dopaminergic grafts. Furthermore, no
      spontaneous recovery was observed in the Y-maze test. These observations show
      that repeated testing can influence the long-term effects of damage to the
      nigrostriatal dopamine system.

PMID- 9522376
TI  - Activation of adenosine A2A and dopamine D1 receptors stimulates cyclic AMP
      dependent phosphorylation of DARPP-32 in distinct populations of striatal
      projection neurons.
AB  - In the striatum, adenosine A2A and dopamine D1 receptors are segregated in
      striatopallidal and striatonigral projection neurons, respectively. In this
      study, we have examined the effects of activating adenosine A2A and dopamine D1
      receptors on the state of phosphorylation of DARPP-32 (dopamine- and cyclic AMP
      regulated phosphoprotein of mol. wt 32,000), a potent endogenous regulator of
      protein phosphatase-1 that is highly expressed in striatal medium-sized spiny
      neurons. In rat striatal slices, the D1 receptor agonist SKF 81297 and the A2A
      receptor agonist CGS 21680 transiently increased the levels of phosphorylated
      DARPP-32 in a concentration-dependent manner. In the same preparation, the two
      agonists were also able to induce a significant increase in cyclic AMP formation.
      When striatal slices were incubated with a combination of CGS 21680 and SKF
      81297, the effects of the two agonists on both DARPP-32 phosphorylation and
      cyclic AMP formation were additive. The maximal effects of SKF 81297 and CGS
      21680 on DARPP-32 phosphorylation were of similar magnitude, and were completely
      abolished by the cyclic AMP-dependent protein kinase inhibitor, Rp-cAMPS. The
      present results show that DARPP-32 phosphorylation in the striatum is stimulated
      by adenosine, acting on A2A receptors, and dopamine, acting on D1 receptors, and
      that cyclic AMP is the mediator in both cases. Our data also suggest that
      dopamine and adenosine regulate the state of phosphorylation of DARPP-32 in
      distinct sub-populations of medium-sized spiny neurons expressing dopamine D1 and
      adenosine A2A receptors, respectively.

PMID- 9522377
TI  - Nerve-induced release of nitric oxide exerts dual effects on nicotinic
      transmission within the coeliac ganglion in the rabbit.
AB  - The involvement of nitric oxide in the modulation of nicotinic activation was
      investigated in vitro in isolated rabbit coeliac ganglion. The electrical
      activity of the ganglionic neurons was recorded using intracellular recording
      techniques. When a train of pulses of supramaximum intensity was applied to the
      splanchnic nerves, gradual depression of fast nicotinic activation occurred: the
      pulses do not systematically elicit action potentials, but very often elicit
      excitatory postsynaptic potentials only. This phenomenon appeared between 15 and
      20 Hz and increased with the frequency of stimulation. It was not related to any
      change in the membrane potential of the ganglionic neurons. For a given
      frequency, the depression appeared progressively and it was particularly strong
      at the end of the train. The use of pharmacological agents that interfere with
      the nitric oxide pathway, such as L-arginine (precursor of nitric oxide), D
      arginine (non-precursor of nitric oxide) N(omega_-nitro-L-arginine and N(omega)
      nitro-L-arginine methyl ester (inhibitors of nitric oxide synthase), and 2-(4
      carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (nitric oxide
      scavenger), demonstrated that nitric oxide modulated this depression phenomenon
      by exerting a dual effect on the nicotinic activation, i.e. facilitation or
      inhibition. Agents interfering with the guanosine 3',5'-cyclic monophosphate
      pathway, such as oxadiazolo[4,3-a] quinoxalin-1-one (selective inhibitor of the
      nitric oxide-activated soluble guanylate cyclase) and zaprinast (selective
      inhibitor of the phosphodiesterases involved in the guanosine 3',5'-cyclic
      monophosphate pathway) demonstrated that only the facilitatory effect of nitric
      oxide on the nicotinic activation was mediated through the guanosine 3',5'-cyclic
      monophosphate pathway. The mechanism sustaining the inhibitory effect remains to
      be determined. By modulating the nicotinic activation, nitric oxide plays a role
      in the integrative properties of the prevertebral ganglia. This opens new
      perspectives with regard to the control of visceral functions by the prevertebral
      level of regulation.

PMID- 9522378
TI  - Somatotopic redistribution of c-fos expressing neurons in the superficial dorsal
      horn after peripheral nerve injury.
AB  - The functional somatotopic reorganization of the lumbar spinal cord dorsal horn
      after nerve injury was studied in the rat by mapping the stimulus-evoked
      distribution of neurons expressing proto-oncogene c-fos. In three different nerve
      injury paradigms, the saphenous nerve was electrically stimulated at C-fibre
      strength at survival times ranging from 40 h to more than six months: 1)
      Saphenous nerve stimulation from three weeks onwards after ipsilateral sciatic
      nerve transection resulted in an increase in the number of Fos-immunoreactive
      neurons within the dorsal horn saphenous territory in laminae I-II, and an
      expansion of the saphenous territory into the denervated sciatic territory until
      14 weeks postinjury. 2) Saphenous nerve stimulation from five days onwards after
      ipsilateral sciatic nerve section combined with saphenous nerve crush resulted in
      an increase in the number of Fos-immunoreactive neurons within the dorsal horn
      saphenous nerve territory, and an expansion of the saphenous nerve territory into
      the denervated sciatic nerve territory. 3) Stimulation of the crushed nerve
      (without previous adjacent nerve section) at five days, but not at eight months
      resulted in a temporary increase in the number of Fos-immunoreactive neurons
      within the territory of the injured nerve, and no change in area at either
      survival time. The results indicate that nerve injury results in an increased
      capacity of afferents in an adjacent uninjured, or regenerating nerve, to excite
      neurons both in its own and in the territory of the permanently injured nerve in
      the dorsal horn. The onset and duration of the increased postsynaptic
      excitability and expansion depends on the types of nerve injuries involved. These
      findings indicate the complexity of the central changes that follows in nerve
      injuries that contain a mixture of uninjured, regenerating and permanently
      destroyed afferents.

PMID- 9522379
TI  - Brain natriuretic peptide-mediated changes in the extracellular neurotransmitter
      turnover in the rostral ventrolateral medulla.
AB  - Changes in the rostral ventrolateral medullary neurotransmitter levels and
      associated cardiovascular functions in response to local administration of brain
      natriuretic peptide were investigated in urethane-anesthetized Sprague-Dawley
      rats. Unilateral injections of various doses of brain natriuretic peptide into
      the rostral ventrolateral medulla region led to significant reductions in both
      blood pressure and heart rate. To identify the changes occurring in the
      extracellular neurochemical profile, brain natriuretic peptide was perfused at
      the rate of 1.5 microliters/min for a period of 1 h through a microdialysis probe
      implanted stereotaxically into the rostral ventrolateral medulla area and the
      dialysate was assayed every 15 min for both catechols and indoleamine. Both
      norepinephrine and epinephrine concentrations were significantly reduced.
      Dihydroxyphenylacetic acid concentration showed no significant change in response
      to brain natriuretic peptide perfusion. On the other hand, serotonin turnover
      estimated by the measurement of its metabolite (5-hydroxyindoleacetic acid)
      concentration increased during the perfusion of brain natriuretic peptide. Blood
      pressure and heart rate also showed significant reduction during the perfusion of
      brain natriuretic peptide. These results suggest that brain natriuretic peptide
      may be relevant in the central regulation of cardiovascular functions by
      modulating monoamine neurotransmitters.

PMID- 9522380
TI  - Projections of pelvic autonomic neurons within the lower bowel of the male rat:
      an anterograde labelling study.
AB  - The tissues of the large intestine which receive an innervation by neurons of the
      major pelvic ganglia were identified following in vivo and in vitro anterograde
      labelling with the lipophilic tracer 1,1'didodecyl-3,3,3',3'
      tetramethylindocarbocyanine perchlorate in the male rat. The primary target in
      the gut of major pelvic ganglion neurons is the myenteric plexus of the distal
      colon and the rectum. The serosal ganglia, on the surface of the most distal
      region of the rectum and the circular muscle of the distal colon and rectum were
      less densely innervated. The pelvic ganglia do not innervate the longitudinal
      muscle, submucosal blood vessels, submucosal plexus, or mucosa. The pelvic supply
      reaches the bowel via two groups of rectal nerves and branches of the penile
      nerves. All of these connections also carry the axons of viscerofugal neurons
      from the bowel, some of which have terminal axons in the major pelvic ganglia.
      Finally, the different nerves supplied different targets. In particular, while
      the rectal nerves carried pelvic axons supplying the myenteric plexus, circular
      muscle, and serosal ganglia, the penile nerves only innervated the serosal
      ganglia. In addition, the two groups of rectal nerves innervated slightly
      different regions of the bowel and provided different projection patterns.
      However, successful in vivo labelling was achieved in only 6/12 animals and while
      all in vitro experiments resulted in successful labelling, it was clear that only
      a proportion of pelvic projections in any given nerve were labelled. These
      studies have shown that the major pelvic ganglia are primarily involved in the
      control of motility, but not of vascular and secretomotor functions. Thus pelvic
      neurons do not innervate the same range of target tissues within the bowel as the
      prevertebral ganglia. This study has also shown that the different pathways to
      the gut from the major pelvic ganglia innervate different tissues, suggesting
      that the autonomic innervation of the gut is not homogeneous along its length.

PMID- 9522381
TI  - Distribution of chromogranins A and B and secretogranin II (secretoneurin) in rat
      pelvic neurons and vas deferens.
AB  - The family of chromogranins/secretogranin peptides comprises three major
      subtypes: chromogranin A, chromogranin B and secretogranin II. We have
      characterized these proteins in rat vas deferens and pelvic ganglia by using two
      approaches. Firstly, extracts of rat vas deferens were subjected to molecular
      sieve chromatography followed by radioimmunoassay. The results indicate that, in
      the peripheral nerves of this organ, chromogranin B and secretogranin II are
      processed to small peptides, i.e. PE-11 and secretoneuron, respectively.
      Secondly, we investigated the localization of each of these peptides in the rat
      pelvic ganglia and vas deferens. Comparisons with the distribution of tyrosine
      hydroxylase, choline acetyltransferase, vesicular acetylcholine transporter and
      SV2 were carried out in double labelling studies. All tyrosine hydroxylase
      positive neurons contained neuropeptide Y, but many neuropeptide Y-containing
      neurons were negative for tyrosine hydroxylase. In the pelvic ganglia,
      chromogranin A was widely localized in the neuropeptide-positive neurons and 65%
      of chromogranin A-containing neurons were positive for tyrosine hydroxylase,
      suggesting their adrenergic nature. However, in nerve terminals of the vas
      deferens, chromogranin A was present at very low, or undetectable, levels. The
      chromogranin B-derived peptide PE-11, on the other hand, was absent from the
      large-sized, tyrosine hydroxylase-positive neurons, but present in some small
      sized neurons that were choline acetyltransferase/vesicular acetylcholine
      transporter-positive and tyrosine hydroxylase-negative. In the vas deferens, PE
      11 was present with intense immunoreactivity in nerve terminals of the lamina
      propria beneath the epithelium, but it was very sparse in the muscular layer and
      co-localized with vesicular acetylcholine transporter-like immunoreactivity,
      suggesting a cholinergic nature. The secretogranin II-derived peptide
      secretoneurin was distributed with strong immunoreactivity in the somata of
      pelvic ganglion neurons, 72% of which also contained tyrosine hydroxylase, as
      well as in nerve terminals in the muscular layer and the lamina propria of the
      vas deferens. Most, if not all, secretoneurin-positive terminals in the pelvic
      ganglia and the vas deferens were positive for choline
      acetyltransferase/vesicular acetylcholine transporter-like immunoreactivity.
      Retrograde tracing with FluoroGold demonstrated that the majority of FluoroGold
      labelled neurons in the pelvic ganglia were positive for either chromogranin A or
      secretoneurin. The present study indicates that chromogranins A and B and
      secretogranin II are proteolytically processed to a high degree in the nerves of
      the rat vas deferens. Furthermore, they are heterogeneously localized in subsets
      of neurons of the pelvic ganglia and in different sets of nerve terminals in the
      vas deferens, suggesting that each of these peptides may play distinct roles in
      neurons of the autonomic nervous system to the vas deferens.

PMID- 9522382
TI  - Spatio-temporal patterns of ensheathing cell differentiation in the rat olfactory
      system during development.
AB  - An immunocytochemical approach with specific glial markers was used to
      investigate the temporal and spatial patterns of differentiation of ensheathing
      glia wrapping axon fascicles along the primary olfactory pathway of the rat
      during development. The two glial markers tested, the proteins S-100 and glial
      fibrillary acidic protein, are known to be expressed at different stages of
      maturation in glial cells. The S-100 protein was first weakly expressed in cells
      accompanying the olfactory axons at embryonic day 14 (E14), while a first faint
      glial fibrillary acidic protein staining was detected along the olfactory axons
      at E15 and along the vomeronasal nerves at E16. A strong S-100 immunoreactivity
      was already present from E16 onwards along the axon fascicles through their
      course in both the nasal mesenchyme and the subarachnoid space before entering
      the olfactory nerve layer of the olfactory bulb. A gradual increase in glial
      fibrillary acidic protein expression was observed along this part of the
      developing olfactory pathway from E16 up to E20, when an adult-like pattern of
      staining intensity was seen. By contrast, most of the ensheathing cells residing
      in the olfactory nerve layer exhibited some delay in their differentiation timing
      and also a noticeable delayed maturation. It was only from E20 onwards that a
      weak to moderate S-100 expression was detected in an increasing number of cells
      throughout this layer, and only few of them appeared weakly glial fibrillary
      acidic protein positive at postnatal days 1 and 5. The immunocytochemical data
      indicate that there is a proximodistal gradient of differentiation of ensheathing
      cells along the developing olfactory pathway. The prolonged immaturity of
      ensheathing cells in the olfactory nerve layer, which coincides with the
      formation of the first glomeruli, might facilitate the sorting out of olfactory
      axons leading to a radical reorganization of afferents before they end in
      specific glomeruli.

PMID- 9522383
TI  - The feasibility of triple-energy absorptiometry for the determination of bone
      mineral, Ca and P in vivo.
AB  - The theoretical feasibility of triple-energy absorptiometry in general and the
      experimental conditions when using triple-energy absorptiometry for the
      determination of bone mineral, elemental calcium and phosphorus content in vivo
      have been investigated. A theoretical analysis of the decomposition of the mass
      attenuation coefficients is presented and discussed. The main obstacle to the
      effective use of triple-energy absorptiometry in vivo is the large number of
      pulses which must be detected to reduce the statistical fluctuations.

PMID- 9522384
TI  - An assessment of the radiation dose to patients and staff from a Lunar Expert-XL
      fan beam densitometer.
AB  - Dual-energy x-ray absorptiometry (DXA) is a widely used technique for measuring
      bone mineral density for the identification and management of osteoporotic
      subjects. The original DXA pencil beam systems expose patients to an effective
      dose of ionizing radiation of around 2 muSv and require no additional protective
      shielding for staff. The new fan beam densitometers incorporate solid state
      detectors and have a higher photon flux, enabling faster acquisition times and
      giving improved resolution. However, this may be at the expense of higher
      radiation dose. This study was conducted to assess the radiation dose to patients
      and staff from the standard scan modes using a Lunar Expert-XL fan beam
      densitometer. This is, we believe, the first dose assessment of the Expert-XL.
      The results indicate that the scatter dose at 1 m from the scan table, assuming
      four AP spine and femoral neck examinations per hour, is about 4 muSv h-1. This
      is well below the limit of 7.5 muSv h-1 set by the UK's Ionising Radiation
      Regulations for defining a Controlled Area but above the lesser limit of 2.5 muSv
      h-1 for a Supervised Area. Typical effective doses to patients are 59 muSv for an
      AP lumbar spine scan, up to 56 muSv for AP femoral neck, 71 muSv for lateral
      spine morphometry and 75 muSv for whole body. Although exceeding those of pencil
      beam DXA machines, these doses are less than for standard radiographic
      procedures, particularly of the lumbar spine. Where reduced scan time, improved
      image resolution or morphometric analysis of the spine are required, the patient
      doses from the Lunar Expert-XL are not prohibitive.

PMID- 9522385
TI  - Influences of lung parenchyma density and thoracic fluid on ventilatory EIT
      measurements.
AB  - Ventilatory impedance changes can be measured by electrical impedance tomography
      (EIT). Several studies have pointed out that the ventilatory-induced impedance
      change measured over the lungs shows a linear relationship with tidal volume.
      However, EIT measures the ventilatory impedance changes relative to a reference.
      Therefore, changes in the reference due to lung parenchyma destruction (increase
      of thoracic impedance) or lung water (decrease of thoracic impedance) might
      influence ventilatory EIT measurements. A study was designed to evaluate the
      influence of the density of lung parenchyma and the thoracic fluid content on
      ventilatory EIT measurements. Eleven emphysema patients with a variable degree of
      lung parenchyma destruction, nine haemodialysis patients with general fluid
      overload and ten healthy subjects were measured. The impedance changes were
      measured with the subject in the supine position breathing a constant tidal
      volume of 1 litre starting at the maximum end-expiratory level. In the emphysema
      group a significantly lower impedance change between ins- and expiration was
      found in comparison with the healthy subjects (11.6 +/- 6.4 AU l-1 versus 18.6 +/
      4.2 AU l-1, p < 0.05), whereas the haemodialysis group showed a significantly
      larger impedance change between ins- and expiration before haemodialysis (30.5 +/
      13.1 AU l-1, p < 0.05). A significant decrease in ventilation-induced impedance
      change during dialysis was found (30.5 +/- 13.1 AU l-1 versus 21.4 +/- 8.6 AU l
      1, p < 0.01). Furthermore, a significant correlation between lung function
      parameters, which indicate the severity of lung parenchyma destruction, and the
      measured impedance change was found in emphysema patients. From these results it
      can be concluded that the density of lung parenchyma and the thoracic fluid
      content have a serious impact on the ventilation-induced impedance change.

PMID- 9522386
TI  - Monitoring relative fluid balance alterations in haemodialysis of diabetic
      patients by electrical impedance.
AB  - Measurements of total-body electrical impedance in the frequency range between
      200 Hz and 300 kHz were performed on 37 diabetic patients undergoing chronic
      haemodialysis. Special attention was paid to the instrument design, where a self
      balancing differential current source was used, reducing considerably the common
      mode voltage at the amplifier input. The patient-instrument interface includes
      screened leads, separately driven by unity-gain buffers. The measurement error
      was < 1% for the impedance within the range of 20 to 1000 omega and < 0.3 degree
      (mean) for the phase angle. Impedance/phase and ultrafiltration measurements were
      carried out throughout the entire procedure. Total and extracellular water were
      computed and compared with extracted fluid volumes. The trends of change of the
      extracellular and intracellular fluid volumes during and immediately after
      dialysis corresponded to the respective clinical condition of the patients and
      enabled us to divide them into four groups. This approach is a step toward
      continuous monitoring and adaptive treatment, tailored to the individual patient
      needs.

PMID- 9522387
TI  - Potential errors in the application of mixture theory to multifrequency
      bioelectrical impedance analysis.
AB  - Potential errors in the application of mixture theory to the analysis of multiple
      frequency bioelectrical impedance data for the determination of body fluid
      volumes are assessed. Potential sources of error include: conductive length;
      tissue fluid resistivity; body density; weight and technical errors of
      measurement. Inclusion of inaccurate estimates of body density and weight
      introduce errors of typically < +/- 3% but incorrect assumptions regarding
      conductive length or fluid resistivities may each incur errors of up to 20%.

PMID- 9522388
TI  - The impedivity of freshly excised human breast tissue.
AB  - A set of 120 impedivity spectra was collected in breast tissue immediately after
      excision from 64 patients undergoing breast surgery. The measurements were made
      at 12 discrete frequencies halving from 1 MHz to 488 Hz. The spectra were sorted
      into three groups of normal tissue, mammary gland, connective tissue and adipose
      tissue, and three groups of pathological tissue, mastopathy, fibroadenoma and
      carcinoma. Intergroup multiple comparisons of the components of impedivity and
      admittivity were systematically carried out at every measurement frequency. The
      low-frequency-limit resistivity, the fractional power and characteristic
      frequencies were calculated from the experimental data. No significant
      correlation between impedivity and admittivity and patient's age was observed,
      except for mastopathy. No significant difference between groups of normal tissue
      and benign pathology (mammary gland, mastopathy and fibroadenoma) was found. The
      group of carcinoma differed from all the other groups principally by the low
      frequency-limit resistivity, the fractional power and the phase angle at
      frequency above 125 kHz. These results indicate that impedance spectroscopy is
      appropriate for the detection of breast cancer.

PMID- 9522389
TI  - Beat-to-beat wavelet variance of the QRS complex as a marker of arrhythmogenic
      substrate in ventricular tachycardia patients.
AB  - This study proposes a wavelet transform based technique to assess the beat-to
      beat variation of the QRS signal in post-myocardial infarction patients with
      sustained monomorphic ventricular tachycardia. Recent electrophysiological
      investigations suggested that the diminished synchrony between the normal
      myocardium and the scarred arrhythmogenic tissue bordering a myocardial
      infarction area gives rise to beat-variable ECG signal components. Using a
      mathematical model of small variations in a largely repetitive waveform, we show
      that the inherent alignment errors (trigger jitter) of the high-resolution ECG
      (HRECG) can artificially increase the value of the time-domain beat-to-beat
      variance, making it less valuable as a marker of beat-variable signal components.
      To overcome this drawback, we propose the wavelet based approach which
      discriminates between the different factors responsible for the beat variability
      (the alignment error and the beat-variable signal components). The Morlet wavelet
      transform is performed on HRECG signals from normal individuals (control group)
      and postmyocardial infarction patients with documented ventricular tachycardia.
      Electrical variability is quantitatively assessed via the beat-to-beat wavelet
      variance measurements. A marker of arrhythmogenic induced variance which achieves
      a good performance in discrimination of ventricular tachycardia patients from
      normal subjects was found between 200 Hz and 300 Hz. This finding is in agreement
      with the proposed mathematical model which states that the useful part of the
      time-frequency map is shifted upward in a precise mathematical way, as the
      variance induced by the beat-variable arrhythmogenic signals depend on the
      frequency characteristics of the first derivative of these signals. We conclude
      that the dynamics of the arrhythmogenic substrate as revealed by the beat-to-beat
      wavelet variance can be a new estimator of ventricular tachycardia risk.

PMID- 9522390
TI  - The variability of the photoplethysmographic signal--a potential method for the
      evaluation of the autonomic nervous system.
AB  - The heart rate variability is composed of low- and high-frequency fluctuations,
      which are mediated by the sympathetic and the parasympathetic nervous systems.
      The baseline and the amplitude of the photoplethysmographic (PPG) signal also
      show fluctuations in the same frequencies. In the current study, PPG examinations
      were performed on the fingers of normal subjects and diabetic patients, and three
      parameters were derived from each PPG pulse: the baseline of the pulse, its
      amplitude and its period (which is equal to the heart period). The level of the
      variability of each PPG pulse parameter was measured by the ratio of the standard
      deviation of the parameter to its mean value. The level of the low-frequency
      fluctuations for the PPG amplitude and for the heart cycle period did not differ
      between males and females, but was lower for diabetic patients, indicating lower
      activity of the autonomic nervous system. The curves of the baseline and the
      amplitude of the PPG signal for the non-diabetic subjects showed high correlation
      between the left and the right hands. For most of the diabetic patients the right
      left correlation coefficients were significantly lower than those for the non
      diabetic subjects. Our initial results have shown that the variability of the PPG
      parameters shows promise for the assessment of the function of the autonomic
      nervous system.

PMID- 9522391
TI  - Postural stability of normal subjects measured by sway magnetometry: pathlength
      and area for the age range 15 to 64 years.
AB  - Fifty-eight subjects with no known vestibular pathology, postural problems or
      cerebrovascular disease were studied to determine the range of sway values in a
      normal working-age population. Sway was measured with a magnetometry system,
      previously shown to be highly successful in distinguishing sway with and without
      the eyes open in individual subjects. 30 subjects were aged 15-29 years and 28
      aged 30-64 years. With the subject standing on a firm base the pathlength and
      area enclosed by movement of the hips in the horizontal plane were measured over
      30 second periods with eyes open and eyes closed. There were no significant
      differences between the two age ranges. We obtained the following upper limits of
      normal values for the age range 15 to 64 years: pathlength with eyes open 140 mm,
      pathlength with eyes closed 200 mm, area with eyes open 150 mm2, and area with
      eyes closed 300 mm2. The mean and standard deviation of the Romberg coefficient
      (sway with eyes open/sway with eyes closed) was 0.73 +/- 0.09 for pathlength
      measurement and 0.70 +/- 0.26 for area measurement.

PMID- 9522392
TI  - Assessment of prematurely born children at follow-up using a tidal breathing
      parameter.
AB  - Prematurely born children frequently have respiratory problems at follow-up. A
      non-invasive and easily performed lung function test would greatly facilitate
      their evaluation and appropriate treatment. We have, therefore, assessed whether
      the shape of the tidal breathing expiratory flow curve would give useful
      information in such a population. One hundred and twenty traces were randomly
      selected from plethysmographic measurements of thoracic gas volume and airway
      resistance made during a follow-up study of a prematurely born population. The
      children had a median gestational age of 29 (range 23-35, interquartile range 27
      31) weeks and postnatal age at the time of measurement of 11 (range 6-24,
      interquartile range 7-13) months. From the flow and volume signals, the mean time
      to reach peak tidal expiratory flow as a proportion of the total expiratory time
      (tPTEF : tE) was determined for each child. The median tPTEF : tE differed
      significantly between children who, in the neonatal period, had or had not
      required mechanical ventilation (p < 0.001) and had or had not had an increased
      inspired oxygen requirement (p < 0.01), and who were or were not symptomatic at
      follow-up (p < 0.001). Logistic regression analysis demonstrated that a low tPTEF
      : tE ratio was independently associated with symptom status. These results
      suggest that assessment of a tidal breathing parameter during follow-up of
      prematurely born children may be useful. As tPTEF : tE can be measured without
      sedation, relatively quickly and with simple equipment, potentially large study
      populations could be investigated, and this technique should now be evaluated in
      a non-sedated group of young prematurely born children.

PMID- 9522393
TI  - Transventricular pressure-velocity wave propagation in diastole: adherence to the
      Moens-Korteweg equation.
AB  - In the latter half of the diastolic phase of the cardiac cycle, the left atrium
      contracts and generates a pressure-velocity wave which enters the left ventricle.
      The wave moves through the inflow tract of the ventricle, reflects off the apex
      and heads towards the aortic valve. The time taken for the pressure-velocity wave
      to propagate through the ventricle, referred to as the A-Ar interval, may be
      measured using pulsed Doppler echocardiography and occurs in the range 20-80 ms.
      It has been shown previously that there is a significant negative linear
      correlation between the A-Ar interval and the passive elastic modulus of the
      ventricular wall (r = -0.782, p < 0.001). This relationship may be explained by
      modelling the left ventricle as a folded-over elastic tube through which the
      pressure-velocity wave is propagated according to the principles of the Moens
      Korteweg equation.

PMID- 9522394
TI  - Molecular biology of glutamate receptors in the central nervous system and their
      role in excitotoxicity, oxidative stress and aging.
AB  - Forty years of research into the function of L-glutamic acid as a
      neurotransmitter in the vertebrate central nervous system (CNS) have uncovered a
      tremendous complexity in the actions of this excitatory neurotransmitter and an
      equally great complexity in the molecular structures of the receptors activated
      by L-glutamate. L-Glutamate is the most widespread excitatory transmitter system
      in the vertebrate CNS and in addition to its actions as a synaptic transmitter it
      produces long-lasting changes in neuronal excitability, synaptic structure and
      function, neuronal migration during development, and neuronal viability. These
      effects are produced through the activation of two general classes of receptors,
      those that form ion channels or "ionotropic" and those that are linked to G
      proteins or "metabotropic". The pharmacological and physiological
      characterization of these various forms over the past two decades has led to the
      definition of three forms of ionotropic receptors, the kainate (KA), AMPA, and
      NMDA receptors, and three groups of metabotropic receptors. Twenty-seven genes
      are now identified for specific subunits of these receptors and another five
      proteins are likely to function as receptor subunits or receptor associated
      proteins. The regulation of expression of these protein subunits, their
      localization in neuronal and glial membranes, and their role in determining the
      physiological properties of glutamate receptors is a fertile field of current
      investigations into the cell and molecular biology of these receptors. Both
      ionotropic and metabotropic receptors are linked to multiple intracellular
      messengers, such as Ca2+, cyclic AMP, reactive oxygen species, and initiate
      multiple signaling cascades that determine neuronal growth, differentiation and
      survival. These cascades of complex molecular events are presented in this
      review.

PMID- 9522395
TI  - An ultrastructural study of the neural circuit between the prefrontal cortex and
      the mediodorsal nucleus of the thalamus.
AB  - Synaptic connectivity between the prefrontal cortex (PFC) and the mediodorsal
      thalamic nucleus (MD) of the rat has been investigated with the electron
      microscope after labeling both the pre- and postsynaptic elements. Prefrontal
      corticothalamic fibers end exclusively as small axon terminals with round
      synaptic vesicles (SR boutons), which make asymmetrical synaptic contacts with
      distal dendritic segments of MD neurons. Thalamocortical terminals from MD in PFC
      are also of the SR type and form asymmetrical synaptic contacts predominantly
      with dendritic spines arising from the apical or basal dendrites of pyramidal
      cells whose somata reside in layers III, V and VI. At least some pyramidal cells
      in layer III that receive MD afferents are callosal cells, whereas deep layer
      pyramidal cells projecting to MD receive directly some of the thalamocortical
      terminations from MD, suggesting that the recurrent loop to MD is
      monosynaptically mediated. Thus, taken together with recent evidence that both
      the PFC-MD and MD-PFC pathways are glutamatergic and excitatory, the cortical
      excitation exerted by afferent fibers from MD is transferred, not only back to MD
      itself through deep pyramidal cells, but also the contralateral prefrontal cortex
      via pyramidal cells in layer III of the ipsilateral prefrontal cortex. Concerning
      modulatory and inhibitory inputs, fibers to MD from the ventral pallidum and
      substantia nigra pars reticulata have been shown to be inhibitory and GABAergic.
      In addition, fibers from the ventral tegmental area preferentially make
      symmetrical membrane thickenings (i.e. inhibitory synapses) on deep pyramidal
      cells in PFC that receive synaptic endings from MD. From these morphological
      grounds, therefore, cells in the ventral pallidum, the substantia nigra pars
      reticulata and the ventral tegmental area may mediate, to some extent, an
      inhibitory effect on the reverberatory excitation between PFC and MD.

PMID- 9522396
TI  - Use of explant cultures of peripheral nerves of adult vertebrates to study axonal
      regeneration in vitro.
AB  - Explanted preparations of peripheral nerves with attached dorsal root ganglia of
      adult mammals and amphibia survive for several days in serum-free medium and can
      be used to study axonal regeneration in vitro. This review outlines the methods
      which we routinely use and how they may be applied to study different aspects of
      axonal regeneration. When the peripheral nerves are crushed in vitro, axons
      regenerate through the crush site into the distal stump within 1 day (mouse) or 3
      days (frog). The outgrowth distance of the leading sensory axons can be
      determined with the use of a simple method based on axonal transport of labelled
      proteins. A compartmentalised system permits selective application of drugs and
      other agents to either ganglia or peripheral nerve containing the regenerating
      axons and has been used to study selected aspects of regeneration including
      influence of non-neuronal cells, retrograde signalling, axonal release of
      proteins during regeneration and the role of phospholipase A2 activity. Explanted
      preparations may also be cultured in a layer of extracellular matrix material
      (matrigel), in which spontaneous outgrowth of a large number of naked axons from
      the cut ends of nerves starts within 1 day and continues for several days. This
      provides an opportunity to study the direct effects of different agents on axonal
      elongation. Preparations cultured in collagen gels show sparse spontaneous axonal
      growth, but this can be increased by addition of certain growth factors. The
      phenotype of the regenerating axons can be studied using immunohistochemical
      methods.

PMID- 9522397
TI  - Adrenalectomy-induced neuronal degeneration.
AB  - The binding of glucocorticoids to CNS receptors results in the modulation of many
      processes, ranging from neurotransmission to cell birth and death. It is of no
      surprise, therefore, that the removal of these steroids following adrenalectomy
      disrupts a variety of physiological functions throughout the brain. It is the aim
      of this review to briefly describe the findings of research examining some of
      these glucocorticoid-mediated CNS effects; however, as many of these areas have
      been reviewed extensively by others, this review will focus on the recently
      described phenomenon, adrenalectomy-induced hippocampal cell death.

PMID- 9522398
TI  - Mood state and cerebral metabolism in persons with age-associated memory
      impairment.
AB  - People undergoing medical procedures sometimes experience feelings that may
      influence the results. In this study, we explore the relationship between changes
      in mood state self-ratings and cerebral glucose metabolism during positron
      emission tomography (PET) in persons with age-associated memory impairment (mean
      age 59.4 +/- 9.8 years). Brain regions of interest involved in both mood and
      memory were examined. Mood ratings of increased boredom correlated significantly
      with mesial temporal and parietal asymmetry and decreased parietal metabolism.
      Mood ratings of increased fatigue correlated with basal ganglia asymmetry and the
      right basal ganglia and left mesial temporal metabolism. These findings suggest
      that subjective mood state changes during PET may influence metabolism in brain
      regions implicated in emotion and memory function in people with age-related
      memory complaints.

PMID- 9522399
TI  - Functional MRI reveals left amygdala activation during emotion.
AB  - The potential of functional magnetic resonance imaging (fMRI) for experimental
      studies of the brain and behavior considerable given its superior time and
      spatial resolution, but few studies have attempted to validate them against
      established methods for measuring cerebral activation. In a previous study
      absolute regional cerebral blood flow was measured in 16 healthy individuals
      using quantitative H215O-PET during standardized happy and sad mood induction and
      during two non-emotional control conditions. During sad mood, blood flow
      increased in the left amygdala and these changes correlated with shifts towards a
      negative affect. In the present study blood oxygenation level dependent (BOLD)
      changes were measured with fMRI during the same experimentally controlled mood
      states and control tasks. Twelve right-handed normal subjects were examined with
      a T2*-weighted FLASH sequence. A significant increase in signal intensity was
      found during sad as well as happy mood induction in the left amygdala. This
      converging evidence supports the potential of fMRI for advancing the
      understanding of neural substrates for emotional experience in humans.

PMID- 9522400
TI  - Frontal CSF enlargement in panic disorder: a qualitative CT-scan study.
AB  - Brain morphology was assessed qualitatively in CT scans of 21 patients with panic
      disorder and 21 normal control subjects. Patients showed significant bilateral
      enlargement of frontal cerebrospinal fluid (CSF) spaces. These findings suggest
      that alterations in brain morphology are involved in the etiology of panic
      disorder.

PMID- 9522401
TI  - Single-voxel 1H-MRS investigation of brain metabolic changes during lactate
      induced panic.
AB  - Intravenous sodium lactate infusion is a robust laboratory technique for
      eliciting panic in susceptible individuals. The objective for this study was to
      replicate previous work which found differential brain lactate rises among
      lactate-sensitive panic subjects relative to control subjects using single-voxel
      1H-magnetic resonance spectroscopy (MRS). Single-voxel 1H-MRS was used to measure
      brain lactate changes in the insular cortex region among 13 panic disorder
      subjects and 10 healthy control subjects during the infusion. One panic subject
      prematurely terminated the study due to a panic response during lactate infusion.
      Data from two additional control subjects and one panic subject were lost due to
      technical problems. Four panic subjects were reinfused with lactate while panic
      free under treatment with fluoxetine (20 mg/day). At the time of initial
      infusion, all subjects were medication-free for at least 1 month. Ten panic
      subjects, but no control subjects, panicked during lactate infusion. In
      comparison to control subjects, panic subjects demonstrated significantly greater
      and prolonged brain lactate rises in the insular cortex region. Three of four
      medicated panic subjects experienced blockage of panic symptoms during lactate
      reinfusion but all exhibited persistent excesses in brain lactate rise.
      Consistent with our prior observations, greater and prolonged lactate rises in
      the insular brain region occur during and following lactate infusion among panic
      subjects compared to control subjects. This differential brain metabolic response
      did not appear to normalize when a small subset of panic patients were reinfused
      following resolution of panic symptoms during treatment over 3-4 months with
      fluoxetine.

PMID- 9522402
TI  - Phosphorus-31 magnetic resonance brain spectroscopy of children at risk for a
      substance use disorder: preliminary results.
AB  - The purpose of this exploratory investigation was to evaluate the heuristic
      potential of 31P magnetic resonance spectroscopy (MRS) in elucidating a
      neurobiologic component of the liability for a substance use disorder (SUD). We
      investigated 31P MRS spectra employing chemical shift imaging (CSI) derived from
      four distinct anatomic brain locations (i.e. frontal, occipital, right parietal,
      left parietal) in three groups of peripubertal children who are hypothesized to
      be at increasing levels of familial SUD risk. Specifically, we studied children
      with a positive paternal family history of SUD and a disruptive behavior disorder
      (DBD) diagnosis (SUD+/DBD+; n = 10), in contrast, to those with a positive
      paternal SUD history in the absence of other psychopathology (SUD+/DBD-; n = 13)
      and matched control children from normal families (SUD-/DBD-; n = 13). In
      addition, we examined neurocognitive tests of our subjects to determine any
      associations between cognitive capacities with regional 31P MRS spectra. The
      highest-risk sample (SUD+/DBD+) demonstrated a diminished proportion of
      phosphodiesters confined to the right parietal voxel. This right parietal
      phosphodiester proportion correlated only with the Information Scale score on a
      standard intelligence test for children. This suggested a relationship between
      general learning ability and motivation for academic achievement and right
      parietal physiology in the highest-risk sample. Variations in synaptic pruning
      could account for this observation.

PMID- 9522403
TI  - Multiple regression analysis of relationship between frontal lobe phosphorus
      metabolism and clinical symptoms in patients with schizophrenia.
AB  - We investigated the differences among diagnostic types of 36 schizophrenic
      patients in the brain phosphorus metabolism in the frontal lobe. We performed
      phosphorus-31 magnetic resonance spectroscopy (31P-MRS) in the frontal region in
      patients with schizophrenia of the catatonic (n = 4), disorganized (n = 8),
      paranoid (n = 10) and undifferentiated (n = 14) types. In the disorganized type,
      the PME level was significantly decreased compared to those in the other three
      types, while the phosphodiester (PDE) level tended to be higher, although not
      significantly, than those in the other types. Using multiple regression analysis,
      we investigated whether or not the clinical symptoms were correlated with the
      brain phosphorus metabolism. An increased motor retardation factor score was
      significantly correlated with decreased PME level, whereas more severe emotional
      withdrawal and blunted affect were associated with increased PDE level. These
      results suggest that altered membrane phospholipid metabolism in the frontal
      region may be associated with negative symptoms and that schizophrenia of the
      disorganized type is associated with more severe negative symptoms and may
      present more severe brain abnormalities compared to the other types.

PMID- 9522404
TI  - Decreased energy demanding processes in the frontal lobes of schizophrenics due
      to neuroleptics? A 31P-magneto-resonance spectroscopic study.
AB  - In the present investigation on 31P-magneto-resonance spectroscopic parameters in
      the frontal lobe, we found phosphocreatine levels and the ratio
      phosphocreatine/adenosine triphosphate to be increased (12.62 +/- 1.98% resp.
      0.31 +/- 0.06) in 50 neuroleptic-treated schizophrenics, whereas no differences
      were detected in 10 neuroleptic-free patients (11.66 +/- 2.57% resp. 0.29 +/-
      0.08) compared to 36 controls (11.37 +/- 1.45 resp. 0.29 +/- 0.04). This result
      points to a major role of neuroleptics in the metabolism of high-energy
      phosphates.

PMID- 9522405
TI  - 'Schizophrenia as a chronic active brain process ...': perhaps, but only in part.

PMID- 9522406
TI  - Neuroimaging of cerebral and cerebellar atrophy in anorexia nervosa.

PMID- 9522407
TI  - Some roots of persistent homosexual fantasy and the quest for father's love:
      conflicted parental identifications in a male patient: fragment of an analysis.
AB  - This is a clinical paper, which includes material from sessions, presenting the
      process of the analysis of a young adult male whose narcissistic character
      patterns, related to and evolved from failed attempts to integrate conflicting
      parental identifications. These unintegrated mother and father identifications
      contributed to life-long latent homosexual fantasies. Rodney's analysis indicates
      that for a boy/man, even a mother who has the qualities of a good enough parent,
      is not good enough to enable him to reach a nonconflicted manhood. A mother
      cannot provide for the boy the male model he needs and is searching for, the male
      who would affirm him in his maleness. Rodney wanted a father on whose shoulders
      he could stand to become a man. Rodney's persistent homosexual fantasy life, his
      quest for father's love, and his search for a masculine object to identify with
      stem from a combination of several factors. Rodney's regression to the negative
      oedipal phase was probably stimulated when father left the family. Rodney was
      eleven at the time. He felt overwhelmed experiencing himself as the oedipal
      victor. Unconsciously, Rodney feared his exacerbated incestuous wishes. He
      projected them upon his mother and subsequently incorporated them in his
      fantasies. His regression to more infantile dependency feelings was defensive.
      Rodney's father was an unsuitable object for identification. He was disinterested
      in Rodney and emotionally unavailable. Rodney, however, sought his father, whose
      lack of loving acknowledgement resulted in a lack of affirmation of Rodney's
      masculinity. Mother provided for Rodney the loving acknowledgement he lacked in
      his relationship with father. She was emotionally sustaining, an energetic,
      vibrant personality, who was seen by Rodney as a "superior human being." Rodney
      consciously idealized his mother toward whom he unconsciously also had ambivalent
      feelings. Rodney's identification with mother was not counterbalanced by the
      presence of a strong, loving father figure whom he could have used as a suitable
      model. This led to the development in Rodney of a strong sense of effeminization.
      Rodney in his homosexual fantasies assumed the so-called "feminine victimized"
      role. The regression to the negative oedipal phase contributed to an exacerbation
      of erotic, father-directed feelings, intensified by the identification with
      mother. Rodney was fixated in his quest for father's love. In addition, Rodney's
      unconscious guilt related to father and mother directed incestuous impulses, and
      his intense aggressivesadistic feelings contributed to the masochistic cast of
      his masturbation fantasies. Rodney's narcissistic aims and the quality of his
      narcissism changed during the analysis. His grandiosity almost disappeared.
      Rodney's goals became realistic and he acquired the skills necessary to achieve
      them. Inhibitions related to the "fear of success" were worked through. This
      enabled Rodney to compete successfully. His healthy narcissism derives from the
      success of his many achievements. Though Rodney remained a basically narcissistic
      personality, he did derive great pleasure from being a giving person. This was
      one of the many ways in which he identified with his mother. At the present,
      Rodney's identifications are selective and do not evoke intrapsychic conflict.

PMID- 9522408
TI  - Psychoanalysis and the myths we work by: a Burkean view.

PMID- 9522409
TI  - Deadly unconscious logics in Joseph Heller's Catch-22.

PMID- 9522410
TI  - Hurtful presences.

PMID- 9522411
TI  - Goodnight moon: repetition and the mastery of separation.

PMID- 9522412
TI  - [Positron-emission tomography in the diagnosis of abdominal tumors].
AB  - PET is recognized as a powerful imaging research tool. Its clinical application
      has been increasing significantly in recent years. Based on pathophysiological
      and biochemical principles, functional PET imaging makes it possible to assess
      parameters of tumor biology not easily accessible to conventional imaging, such
      as metabolic activity, proliferation, adrenergic transmitter uptake or
      accumulation of cytostatics in individual tumor manifestations. For clinical
      application, PET imaging with 2-[F-18]fluorodeoxyglucose (FDG) is of paramount
      importance. This article reviews recent developments in the use of PET in the
      diagnosis of abdominal malignant tumors. Diagnosis of pancreatic carcinoma and
      related liver metastases, locoregional and distant recurrence, as well as therapy
      control of colorectal cancer, nodal and extranodal staging and therapy monitoring
      of malignant lymphoma, can be reliably performed with PET. Several appropriately
      labeled adrenergic transmitters are currently being developed for specific
      imaging of neuroendocrine tumors. Radiolabeled cytostatics such as F-18 5-FU will
      shortly be available for clinical use as probes for primary or secondary
      cytostatic resistance. Encouraging clinical results and attractive new imaging
      concepts promise increasing use and importance for PET for imaging of abdominal
      malignancies.

PMID- 9522413
TI  - Imaging of the small intestine.
AB  - Endoscopy is not yet a practical procedure for examining the small intestine. A
      variety of radiological techniques are available for investigating suspected
      small intestinal disorders. Plain radiographs are the initial procedure in
      patients who present acutely, and barium studies are mostly used in the patients
      who present less acutely. Enteroclysis (small bowel enema) is proving to be an
      accurate barium technique. Computed tomography (CT) is useful in certain cases,
      particularly in established intestinal obstruction, while angiography and
      radionuclide studies can be extremely useful in suspected intestinal bleeding.
      Ultrasound has a limited role in the investigation of intestinal disorders.

PMID- 9522414
TI  - [Gamma knife radiosurgery in neurosurgery].
AB  - The gamma knife is a stereotactic radiosurgery device which allows well defined,
      deep seated brain tumors, or arteriovenous malformations having a diameter of
      less than 3 cm, to be treated in a single session under local anesthesia. This
      technique, which was first described over 40 years ago, has undergone major
      development in recent years and is the most commonly used method for radiosurgery
      worldwide. The principle relies on the over-lapping of narrow collimated beams
      from 201 cobalt-60 sources. The technique, which was introduced into Switzerland
      in September 1994, has rapidly gained recognition. 184 patients have been treated
      by 30 April 1997. An average follow-up period of 15 months is much too short for
      analysis of patients treated by radiosurgery. However, our series of benign
      tumors shows stabilization of volume in the first few months followed by a slow
      reduction of the tumor volume, in all but two cases. The gamma knife represents
      the treatment of choice for recurrent and unsuccessfully operated patients with
      endocrine active pituitary adenomas. With brain metastases, a rapid reduction in
      tumor volume is seen in the first few weeks in the majority of cases. The tumor
      volume may then remain stable or reduce further until complete disappearance. In
      the case of arteriovenous malformations complete obliteration of the nidus is not
      seen, on average, for 2-3 years. Individual patient follow-up studies illustrate
      these results. To date our results have shown zero morbidity and mortality.
      International statistics from 58,766 cases (as of December 1996) from 77 gamma
      knife centers demonstrate the value of this technique as a complement or,
      depending on the indication, an alternative to classical microsurgery.

PMID- 9522415
TI  - [Computer in radiation oncology: a review].
AB  - In radiation oncology the computer has its confirmed importance for many
      activities and now appears indispensable. Many applications in treatment planning
      and during treatment are only possible with its support. The most important
      applications of the computer in a radiation oncology centre are reviewed. A
      computer-network of the different subsystems involves advantages and improves
      work flow security. Two future applications under development are presented:
      dynamic treatment, and inverse treatment planning. Treatment of the individual
      patient is a matter of co-decision by all concerned. The computer is an auxiliary
      resource which offers greater facility, increases safety and improves accuracy.

PMID- 9522416
TI  - [Half of a diagnosis].

PMID- 9522417
TI  - [Re: Whiplash injury of the cervical spine. Tha value of modern imaging methods,
      by Nidecker A, Pernus B, Hayek J. Ettlin T. Schweiz Med Wochenschrift 1997;
      127:1643-51].

PMID- 9522418
TI  - Epidemiological survey in hay fever patients: symptom prevalence and severity and
      influence on patient management.
AB  - The prevalence and severity of symptoms of self-reported hay fever were assessed
      in 509 symptomatic patients not currently receiving treatment who consulted their
      physicians in Switzerland during the 1994 pollen season. Conjunctivitis was
      diagnosed in 93.3% of cases (in 8% isolated), rhinitis in 92% (isolated in 6.7%).
      24.2% suffered from current asthma symptoms. The severity of the asthma symptoms
      was mild in 43.9%, moderate in 48% and severe in 8.1%. When the main
      symptomatology of hay fever (excluding asthma) was taken into account (the
      diagnosis with the severest symptomatology), 22.4% of patients suffered
      predominantly from conjunctivitis, 24.6% from rhinitis and 53% from both. Onset
      of symptoms typically occurred between March and May and lasted on average 2.7 +/
      1.8 months. Severe symptoms were most common in the rhinitis group and least
      common in the rhinoconjunctivitis group. Conjunctivitis was more common than
      rhinitis in younger patients, whilst asthma prevalence increased with age (so
      called "Etagenwechsel"). Topical therapy was the preferred treatment for all
      three symptomatologies and particularly for conjunctivitis. Overall, topical
      therapy was recommended for 50.5% of patients and in a further 33% in combination
      with oral therapy. In conclusion, conjunctivitis symptoms are at least as severe
      as rhinitis symptoms in approximately 70% of patients with hay fever. This would
      appear to influence clinical management as indicated by a preference for topical
      therapy.

PMID- 9522420
TI  - [Air pollution and health--data from Switzerland].

PMID- 9522419
TI  - [Importance of endoscopic hemostasis in peptic ulcer hemorrhage in a teaching
      hospital].
AB  - INTRODUCTION: The results of endoscopic treatment for bleeding peptic ulcers in a
      teaching hospital are little reported. Most studies are published by a limited
      number of specialized authors with a reported success rate of 76-83%. The aim of
      this study is to evaluate the success rate in a teaching hospital. PATIENTS AND
      METHOD: We retrospectively studied 150 patients hospitalized in our service
      between 1994 and 1995. They comprised 59 females (median age 80.5 [24-93] years)
      and 91 males (median age 61.5 [26-98]). 49% were aged 70 or over. 39 patients
      (29%) had a past history of peptic ulcer disease, the others being admitted for
      an initial episode of bleeding ulcer. Biopsies for urease test were obtained in
      84 patients. In this group the prevalence of Helicobacter pylori infection was
      respectively 88% and 58% in subjects with a history of ulcer disease and in those
      with an initial episode of bleeding ulcer. 46% and 54% respectively had taken
      nonsteroidal anti-inflammatory drugs during the previous weeks. Neither of these
      two risk factors was present in 9 patients without a previous history of ulcer
      disease; they were present in none of those with a history. RESULTS: All patients
      underwent emergency esogastroduodenoscopy; 48 underwent endoscopic hemostasis. 12
      gastroenterologists were involved in these procedures. The definitive success
      rate is 81%. The success rate for a first hemostasis for a posterior bulbar ulcer
      is 41% vs 88% for the other localizations, a difference which is statistically
      significant (p = 0.002). Endoscopic hemostasis showed a higher failure rate where
      the bleeding stigmata was a spurting vessel (44% vs 18%) but this was not
      significant (p = 0.18). CONCLUSION: Endoscopic treatment for bleeding peptic
      ulcer is effective in a teaching hospital. The technique shows a higher failure
      rate for posterior bulbar ulcers. In view of the risk of recurrence, patients
      should be kept in hospital after a first procedure.

PMID- 9522421
TI  - [Swiss Study on Air Pollution and Lung Diseases in Adults (SAPALDIA)].
AB  - Long-term health effects of moderate ambient air pollution are rarely
      investigated. In Switzerland, no large-scale study has addressed this issue so
      far. Important results of the Swiss Study on Air Pollution and Lung Disease in
      Adults (SAPALDIA) are presented. During the period 1991-1993, SAPALDIA
      investigated a random population sample (18-60 years) in eight Swiss areas with
      different environmental characteristics (Aarau, Basel, Davos, Geneva, Lugano,
      Montana, Payerne, Wald). In total, 9651 adults (60%) participated in the cross
      sectional investigation (part 1, 1991), consisting of the following standardized
      procedures: questionnaire (interview), forced expiratory lung function test,
      bronchial challenge with methacholine, atopy assessment (Phadiatop, unspecific
      total IgE), allergy skin tests, and endexpiratory CO-measurements. Subjects with
      a history of respiratory symptoms, increased bronchial reactivity, reduced lung
      function (FEV1/FVC < 80% predicted) and 150 healthy never-smokers were included
      in the subsequent diary study (part 2; n = 3281, 1992/93). Peak flow (morning and
      evening), symptoms, medication, personal activity and visits to the doctor were
      monitored. Across regions, annual mean values ranged from 9 to 52 mg/m3 (NO2) and
      10 to 33 mg/m3 (PM10) respectively. Air pollution had effects on prevalence of
      dyspnea (+41% per 10 mg/m3 increment of the annual mean PM10, 95% CI 20-65%), on
      symptoms of chronic bronchitis (+31%, 10-55%), on FVC (-3.1%; -3.7 to -2.6%), and
      FEV1 (-1.1%; -1.7% to -0.5%), on the incidence of respiratory symptoms and the
      length of symptomfree intervals (11% change per 10 mg/m3 PM10), but not on the
      prevalence of asthma. Environmental tobacco smoke (ETS) showed impact on wheezing
      (OR 1.94; 1.39-2.70), asthma (1.39; 1.04-1.86), bronchitis (1.60; 1.24-2.08) and
      chronic bronchitis (1.50; 1.11-2.02). Health effects of moderate air pollution
      were confirmed in Switzerland. Although for the individual the relative risks are
      small, the public health impact may be considerable. An ongoing follow-up will
      investigate the mortality profile of the SAPALDIA cohort.

PMID- 9522422
TI  - [Swiss journey through the clinical and genetic characteristics of diabetes in
      young patients].
AB  - The aim of this study is to understand better the genetic causes of type II
      diabetes and the phenotypic consequences of the genetic changes. We first
      investigated the relative prevalence of the different forms of diabetes in young
      adults and their clinical features. 51 non-obese patients were identified in whom
      diabetes had been diagnosed before age 40; cases of typical insulin-dependent
      type I diabetes were excluded. A search for mutations of the glucokinase and HNF
      1 alpha genes and for mitochondrial DNA was made, anti-islet and anti-GAD
      antibodies were determined and HLA class II genotyping was performed. Patients
      were subdivided on clinical grounds into a MODY (maturity onset diabetes of the
      young) group (n = 19) and a non-MODY group (n = 32). MODY is a form of diabetes
      which has an autosomal dominant inheritance for which 3 genes have already been
      implicated (MODY1, HNF-4 gene; MODY2, glucokinase gene, and MODY3, HNF-1 alpha
      gene). In the MODY group we identified 3 patients with MODY2, 1 with MODY3, 1
      with the 3243 mitochondrial mutation and a further patient with autoimmune
      diabetes. In the non-MODY group we found 5 patients with autoimmune diabetes and
      1 with MODY2. No clinical parameter was helpful in classifying patients in one of
      these subclasses of diabetes; however, glucagon stimulated C-peptide was useful
      in discriminating between MODY2 patients and the others. Young and lean non
      insulin-dependent diabetic patients thus constitute a very heterogeneous group,
      though presenting similar clinical features. In the second study we analyzed
      hepatic glucose metabolism in patients with a mutation of the glucokinase gene
      expressed in both liver and islet beta cells. We found that endogenous glucose
      production is inadequately inhibited by hyperglycemia, a fact which contributes
      to the pathogenesis of hyperglycemia in these patients.

PMID- 9522423
TI  - [Tumor in the abdomen. II].

PMID- 9522424
TI  - Over the hill and far away: distance as a barrier to the provision of assistance
      to elderly relatives.
AB  - This paper considers the impact of the distance between employed caregivers and
      their elderly relatives on the provision of various forms of family-based
      assistance ("eldercare"), and in so doing it contributes to two overlapping
      literatures, one on the geography of care for elderly persons and the other on
      eldercare as a "work and family" issue. The paper also seeks to interpret and
      understand the spatiality of eldercare in light of evolving public policy on the
      care of dependent populations, and does so with an eye to the highly gendered
      nature of family caregiving. The empirical portion of the paper draws on a
      national survey of work and family conducted by CARNET (The Canadian Aging
      Research Network). Analysis of data for 1149 respondents with eldercare
      responsibilities reveals significant distance-decay effects in the average
      (weekly) number of hours devoted to eldercare. However, disaggregation by gender
      reveals that only male caregivers display this normative behaviour. Analysis of
      the average time-distances at which particular types of assistance are provided
      reveals a similar "gender gap"--women are willing to travel farther, more often,
      than male caregivers. The results suggest that the reconceptualization of aging
      as a "private" problem, to be attended to (by women) in the family and community,
      will particularly affect the careers and family lives of female caregivers, for
      they are more likely than their male counterparts to take on more travel and try
      to squeeze more into already tight time budgets.

PMID- 9522425
TI  - Intellectual intersections: gender and health in the Pacific.
AB  - Intriguing intellectual intersections offer the promise of enriching medical
      geography and making it both more theoretically sophisticated and more policy
      relevant. Employing a socio-ecological model of health, this paper explores
      several of these intersections, including the incorporation of gender into our
      research frameworks. As a context, the complex reasons for the increased interest
      in women's health over the past two decades, including the persistent tensions
      surrounding this interest, are reviewed. Drawing not only from conventional
      sources but also from literature on gender relations, domestic violence and aging
      in the Pacific as well as recent reports on health and socioeconomic development,
      key issues for women's health in the Pacific Islands are addressed.

PMID- 9522426
TI  - Cultural constraints on the delivery of HIV/AIDS prevention in Ireland.
AB  - HIV appeared in Ireland following an opiate epidemic in the early 1980s.
      Initially, however, the gay community mounted the only response to the spread of
      the virus while the implementation of early actions by the government was
      hampered by the constructions of the disease within Irish society. This paper
      considers the influence of the religious hierarchy in both the development of
      AIDS policy and in the shaping of public perceptions of the disease and those
      affected. A qualitative methodology is used to examine the role of such cultural
      constraints in an evaluation of the social context within which the prevention of
      HIV infection occurs. Three key issues pertinent to the policy context in Ireland
      are explored in depth. These are the role of the Catholic Church, the influences
      on health education programmes, particularly information giving, and the
      development of services and other interventions. These findings are discussed
      within the social and political contexts in which health policy is formulated.

PMID- 9522427
TI  - Tuberculosis mortality in England and Wales during 1982-1992: its association
      with poverty, ethnicity and AIDS.
AB  - This paper seeks to establish the strength of association between contemporary
      tuberculosis (TB) in England and Wales and several potential aetiological
      factors. It presents an ecological analysis of standardised annual TB mortality
      rates for the 403 local authority districts between 1982 and 1992, disaggregated
      by age and sex. Social, demographic and ethnicity measures from the 1981 and 1991
      censuses and standardised annual AIDS-related mortality rates for young men are
      used to calculate Poisson regression models. A strong association was found
      between all TB mortality groups and overcrowding at the household level. For
      women, no other measures improved the explanatory power of the models. In
      multiple regressions, both poverty and AIDS-related mortality explained
      additional variation in the model for younger men. The link between ethnicity and
      tuberculosis notifications was not reflected in this analysis of mortality. For
      all groups no evidence of a positive relationship with ethnicity was found, once
      overcrowding had been accounted for. The significance of household as opposed to
      district level crowding suggests that prolonged contact is required for disease
      transmission. Regression analysis indicates that it is the overcrowding and
      poverty among ethnic populations that is significant for their tuberculosis
      mortality. The fact that the relationship between AIDS and TB is confined to the
      group most typical of AIDS patients provides evidence that AIDS has little
      influence on the level of tuberculosis mortality in the wider population.
      Explanations for the observed relationship include preferential certification,
      migration for treatment and shortcomings in health care provision.

PMID- 9522428
TI  - Hypothesized foetal and early life influences on adult heart disease mortality:
      an ecological analysis of data for the Republic of Ireland.
AB  - Spatial disparities in the prevalence of heart disease are frequently explained
      in terms of adult lifestyle factors (e.g. diet, smoking, alcohol consumption,
      stress, exercise, etc.). However, research in recent years suggests an
      alternative explanation: namely, that the risk of heart disease in adult life may
      be influenced either by living conditions shortly after birth or by foetal
      development before birth. This paper outlines the evolution of this line of
      thought, and tests whether these hypotheses are consistent with ecological data
      for deaths from ischaemic heart disease between 1981 and 1990 and infant deaths
      between 1916 and 1935 in the Republic of Ireland. Support for the hypotheses is
      found to be ambiguous. Possible interpretations of these findings are discussed,
      paying particular attention to the anomalous nature of infant mortality in
      Ireland between 1916 and 1935.

PMID- 9522429
TI  - Multi-drug resistant tuberculosis in Finland--a forecast.
AB  - Since the collapse of the Soviet system, travel between the St Petersburg
      district and the Baltic states and Finland has increased substantially. Although
      it is difficult to obtain exact figures on the number of cases of tuberculosis
      (TB) and multi-drug resistant (MDR) TB in these countries, there is strong
      evidence of growing epidemics, bringing added epidemiological threat to Finland.
      The purpose of this study is to produce a short-term "worst case" forecast of the
      spatial development of a threatened MDR-TB epidemic in Finland. The method
      applied is a chorological multistep procedure using statistical and geographical
      methods and a simulation technique. Instead of focusing on populations of
      carriers and susceptibles, emphasis is placed on identifying the primary
      influences directing the epidemic as a spatial process. This was done by dividing
      Finland into small-area units and by assigning the risk of obtaining MDR-TB to
      each unit based on socioeconomic and structural characteristics of the
      population. The simulated 6 year cumulative distribution of new MDR-TB cases
      showed a marked concentration of cases in the capital region and in a cluster of
      municipalities along the west coast. Although socioeconomic factors are important
      in explaining the distribution of cases, frequent and widespread international
      contacts seemed to be equally important at the beginning of the epidemic.

PMID- 9522430
TI  - Geographical variation in attitudes towards smoking: findings from the COMMIT
      communities.
AB  - This paper examines the links between attitudes towards cigarette smoking and the
      social environments of communities involved in the U.S. National Cancer
      Institute's Community Intervention Trial for Smoking Cessation (COMMIT). Our
      objective is to identify sources of social-geographic variation in smoking
      attitudes and norms which can hinder or enhance public health efforts to reduce
      tobacco use. The analysis had two stages: (1) place (measured as region and
      community) was identified as an important main effect accounting for individual
      variation in smoking attitudes independent of smoking status and personal
      characteristics; (2) case studies of COMMIT sites in North Carolina, Iowa,
      Washington, New Jersey and New Mexico were conducted to reveal features of the
      local milieux which could account for variations in smoking attitudes. Some of
      the place characteristics that we suggest are linked to local attitudes include
      economic reliance on the tobacco industry, libertarian political orientations,
      socio-economic conditions, legislative context and ethnic composition. Given the
      effects of regional and community attributes on individual attitudes towards
      smoking, we conclude that public health efforts to control smoking should
      continue to be targeted beyond individual smokers to the broader social
      environment.

PMID- 9522431
TI  - The public health risks of Lyme disease in Breckland, U.K.: an investigation of
      environmental and social factors.
AB  - This paper considers the public health risks of Lyme disease, a borrelial
      infection transmitted to humans chiefly by nymphal Ixodes ticks. A study
      undertaken in the Breckland area of East Anglia, U.K., combined analysis of the
      spatial and temporal factors affecting tick activity at recreational sites with a
      survey of current levels of disease awareness among visitors to these locations.
      Significant relationships were found between densities of questing ticks and
      vegetation type, relative humidity and temperature. More than two thirds of the
      general public visiting the sites were aware ticks could carry diseases, but only
      13% recognized an unfed nymph, and under half knew that Lyme disease could be
      contracted from tick bites. Such results need to be taken into account when
      formulating public health and education measures.

PMID- 9522432
TI  - The problem of atopic eczema: aetiological clues from the environment and
      lifestyles.
AB  - Atopic eczema is the most common inflammatory skin disease in children, affecting
      around 10% of children in the developed world. It can be a distressing condition,
      influencing children's well-being, personal and educational development, and
      family life, and it has huge economic implications for health services and
      individual budgets. Like other atopic diseases such as asthma and hay fever, the
      prevalence of atopic eczema has increased substantially over the last 30 years,
      for reasons largely unknown. Although a genetic predisposition to the disease has
      been implicated, evidence from a range of sources suggests that environmental
      factors play a crucial role in the disease expression. This paper reviews the
      epidemiology of atopic eczema, with particular attention to potential
      environmental aetiological factors and draws evidence from studies in the UK and
      internationally. First, atopic eczema has been found to vary socially and to be
      more prevalent in the UK among social class I and II families than among other
      socio-economic groups. Second, it has been suggested that cross infection from
      other siblings in large families may have a protective role in atopic disease
      expression. Third, it has been proposed that an increased risk of atopic eczema
      may result from decreases in helminthic infestation. Fourth, studies of migrant
      groups have shown large increases in disease prevalence compared with migrants'
      country of origin, suggesting clues as to the importance of socio-economic and
      environmental changes such as those associated with industrialization. Finally, a
      distinct and consistent geographical pattern of eczema has been observed in the
      UK which cannot be explained by social class distribution. The various types of
      study have attempted to identify reasons for differences in prevalence but, to
      date, no definitive causation has been identified. In some cases, specific risk
      factors have been suggested and include house dust mites, dietary allergens and
      irritants. It is argued here that the aetiology is unlikely to be simple or uni
      causal and that an understanding of the relationships between the disease and
      behaviour, lifestyle, home and external environmental factors is crucial. This
      paper reports the preliminary stages of an interdisciplinary research project
      involving dermatologists, epidemiologists and health geographers, and calls for
      investigation into associations between atopic eczema and possible environmental
      and lifestyle factors. These include behavioural factors, microenvironment
      factors and macroenvironments.

PMID- 9522433
TI  - Pathways of dependence: the impact of health and social care restructuring--the
      voluntary experience.
AB  - The current emphasis on community over institutionally based modes of health and
      social care delivery in the UK, together with legislative change, has placed a
      renewed emphasis on the role of the informal sector in service provision.
      Simultaneously, there has been an attempt to modify the provider-role of the
      statutory sector, in favour of an evolving role as purchaser and enabler of
      independently provided services. Drawing on material that forms part of a 3 year
      study into health and social care restructuring, and its effect on the caring
      networks of elderly dependent populations, this paper focuses on the changing
      role of the voluntary sector. Using empirical material drawn from the Scottish
      environment, it illustrates how the restructuring process may be modifying the
      voluntary sector and contributing to a growth in geographical inequity in
      voluntary service provision. In doing so, it considers four main factors
      affecting local voluntary organisations--the growth of contracting, external
      constraints on voluntary provisioning, the influence of the local authority and
      Wolch's concept of the "Shadow State". It highlights the emerging social and
      spatial manifestations arising from such change, and how these modifications may
      also be contributing to a growth in geographical inequity for service recipients
      linked within the dependence network.

PMID- 9522434
TI  - The study of human behavior and schistosomiasis transmission in an irrigated area
      in Morocco.
AB  - This paper presents a research strategy for studying water contact, water use and
      schistosomiasis transmission in an irrigated area of Morocco. This setting, with
      many scattered water contact sites, many activities carried out at these sites,
      and the small number of people involved, was not appropriate for a conventional
      water contact study based on the observation of water contact sites, such as had
      been carried out in the Nile delta. The Moroccan study utilizes three related
      concepts: the household, time geography, and the gendered use of space. It seeks
      to understand processes and interrelationships underlying the daily mobility
      pattern of individual households, and seen as part of a larger system of
      organization and structure in time and space. The preliminary results of the
      study indicated the complexity and dynamism of water use and water contact, which
      need to be considered in planning disease control strategies especially in
      changing settings, such as those associated with environmental interventions in
      the study area.

PMID- 9522435
TI  - Alfred Haviland's nineteenth-century map analysis of the geographical
      distribution of diseases in England and Wales.
AB  - The nineteenth-century English physician Alfred Haviland used the national
      mortality statistics for England and Wales to develop an elaborate geographical
      explanation based on map analysis for the cause of heart, cancer, and
      tuberculosis deaths. He found that females had higher rates for all three causes
      of death. However, although his technique was innovative his analysis was flawed.

PMID- 9522436
TI  - Roles of two allelic variants (Arg144Cys and Ile359Leu) of cytochrome P4502C9 in
      the oxidation of tolbutamide and warfarin by human liver microsomes.
AB  - 1. Tolbutamide methyl hydroxylation and racemic warfarin 7-hydroxylation
      activities were determined in liver microsomes of 39 Japanese and 45 Caucasians
      genotyped for the cytochrome P450 (P450 or CYP) 2C9 gene into three groups,
      namely the wild-type (Arg144.Ile359), and two heterozygous Cys allele
      (Cys144.Ile359) and Leu allele (Arg144.Leu359) variants. 2. Good correlations
      were found between tolbutamide methyl hydroxylation and racemic warfarin 7
      hydroxylation activities in liver microsomes of Japanese and Caucasians. Humans
      with the Cys allele CYP2C9 variant, which was detected in 22% of Caucasians, were
      found to have similar catalytic rates to those of the wild-type in the oxidations
      of tolbutamide and racemic warfarin, whereas humans with the Leu allele, which
      was detected in 8% Japanese and 7% Caucasian samples, had lower catalytic rates
      than those of other two groups. 3. The rates of 6- and 7-hydroxylation of racemic
      warfarin were correlated well with those of S-warfarin, but not R-warfarin, in
      human liver microsomes. 4. Both human liver microsomes and recombinant CYP2C9
      catalysed 7-hydroxylation of S-warfarin more extensively than those of R
      warfarin. K(m)'s for the 7-hydroxylation of S-warfarin were not very different in
      liver microsomes of humans with these three genotypes. Anti-CYP2C9 antibodies and
      sulphaphenazole inhibited the 6- and 7-hydroxylation of S-warfarin, but not R
      warfarin, by > 90% and the methyl hydroxylation of tolbutamide by about 50%. 5.
      These results suggest that humans with Leu allele of CYP2C9 have lower Vmax's for
      S-warfarin 7-hydroxylation and tolbutamide methyl hydroxylation than those with
      wild-type and Cys allele CYP2C9, although the K(m)'s are not very different in
      liver microsomes of these three groups of humans. R-warfarin hydroxylation may be
      catalysed by P450 enzymes other than CYP2C9 in man.

PMID- 9522437
TI  - Inhibition of 7-ethoxycoumarin O-deethylase activity in rat liver microsomes by
      naturally occurring flavonoids: structure-activity relationships.
AB  - 1. The inhibitory effects of several naturally occurring flavonoids and related
      compounds on cytochrome P450-dependent 7-ethoxycoumarin O-deethylase (ECOD) and
      the structure-activity relationships were studied in liver microsomes from rats
      treated with 3-methylcholanthrene (MC). 2. All the flavonoids (flavone, apigenin,
      chrysin, flavonol, fisetin, kaempferol, morin, myrisetin, quercetin, flavanone,
      hesperetin and naringenin) studied inhibited microsomal ECOD activity in the
      following order: flavones > flavonols > flavanones, were mixed type inhibitors
      and had Ki in the range of 0.17-4.5 microM. (+/-)-Catechin had no effect. 3. The
      double bond between C2 and C3 of the C ring, the keto group and hydroxyl group of
      this ring in the flavonoids seem to play major roles in inhibiting the ECOD
      activity. 4. The hydroxyl groups in the C5 and C7 positions of A ring in the
      flavone and the hydroxyl group in the C3 position of C ring in the flavonol
      classes, respectively, were important factors for the inhibition of the enzyme.
      5. In a series of 3, 5, 7-trihydroxyflavones, the hydroxyl group at the C4 in the
      B ring was also an important factor for the inhibition of ECOD activity, but
      hydroxyl groups in other positions of the B ring had little effect on the
      inhibition. 6. We conclude that all the flavonoids studied inhibit ECOD activity
      by interfering with the binding of substrate to the active site and other site(s)
      of the enzyme and that their structural differences lead to different binding
      affinities at the active site and possibly to binding at other site(s) of the
      enzyme for the flavonoids.

PMID- 9522438
TI  - Diastereospecific kinetics of nicotine N'-oxidation in rat liver microsomes.
AB  - 1. In kinetic studies, both Eadie-Hofstee plots for cis- and trans-nicotine-1'-N
      oxide formation from nicotine in rat liver microsomes were linear. For the
      formation of cis- and trans-nicotine-1'-N-oxide, the apparent K(m) were 0.240 +/-
      0.069 and 1.524 +/- 0.951 mM respectively. Corresponding Vmax were 1.52 +/- 0.48
      and 1.19 +/- 0.74 nmol/mg/min respectively. 2. The formation of cis-nicotine-1'-N
      oxide was greater than the formation of trans-nicotine-1'-N-oxide in rat liver
      microsomes and the intrinsic clearance of cis-nicotine-1'-N-oxide formation was
      8.1-fold greater than that of trans-nicotine-1'-N-oxide formation. 3. The
      formation of both cis- and trans-nicotine-1'-N-oxide in rat liver microsomes was
      inhibited by the addition of 1-(1-naphthyl)-2-thiourea or by heat-treatment of
      microsomes. 2-Diethylaminoethyl-2, 2-diphenylvalerate (SKF525A) and carbon
      monoxide did not affect these activities even at high concentrations. 4.
      Formations of cis- and trans-nicotine-1'-N-oxide correlated significantly with
      each other (r = 0.862, p < 0.01). These results suggested that the same flavin
      containing monooxygenase (FMO) isoform is responsible for the formation of cis-
      and trans-nicotine-1'-N-oxide in rat liver.

PMID- 9522439
TI  - Baculovirus-mediated expression of cytochrome P4502C8 and human NADPH-cytochrome
      P450 reductase: optimization of protein expression.
AB  - 1. High expression levels of cytochrome P450 (CYP) 2C8 and NADPH-cytochrome P450
      oxidoreductase (OxR) in Spodoptera frugiperda (Sf21) cells have been achieved
      using the baculovirus expression system. 2. The baculovirus dual expression
      plasmid, pAcUW31, was used to insert CYP2C8 and OxR cDNAs downstream of the
      polyhedrin (polh) or p10 promoters, either separately or together, generating
      four recombinant baculoviruses; two expressing single proteins (CYP2C8 driven by
      the p10 promoter, bVp10.2C8 or OxR driven by the polh promoter, bVpolh.OxR) with
      another two coexpressing both CYP2C8 and OxR under reciprocal control of the polh
      and p10 promoters (bVpolh.OxR-p10.2C8 and bVpolh.2C8-p10.OxR). 3. High levels of
      singly expressed CYP2C8 and OxR were achieved from bVp10.2C8 and bVpolh.OxR, with
      levels of 0.7-1.2 nmol CYP/mg protein and 400-500 nmol cytochrome c
      reduced/min/mg protein respectively. 4. The two dual gene clones (bVpolh.OxR
      p10.2C8 and bVpolh.2C8-p10.OxR) showed, in general, greater variation in CYP
      content and OxR activity than single gene clones. Screening was therefore
      necessary for the selection of dual gene clones expressing both proteins
      optimally. 5. Sf21 microsomes infected by selected dual gene clones were, on
      average, 14 times more active in tolbutamide hydroxylase activity than those
      expressing CYP2C8 alone, with a mean spectral CYP content of 79 pmol/mg cell
      lysate protein and a mean OxR level of 600 nmol/min/mg cell lysate protein.

PMID- 9522440
TI  - Metabolism of droloxifene in the CD-1 mouse, Fischer-344 rat and cynomolgus
      monkey.
AB  - 1. The fate of [14C]droloxifene, a novel non-steroidal anti-oestrogen, was
      studied following oral administration to the CD-1 mouse, F-344 rat and Cynomolgus
      monkey. 2. Most of the radioactivity was primarily excreted in the faeces and
      urine was the minor route of excretion. 3. Droloxifene was extensively
      metabolized in all three species, primarily by two metabolic pathways;
      glucuronidation of unchanged droloxifene and oxidative metabolism, presumably by
      cytochrome P450. 4. In mouse, oxidative metabolism followed by conjugation played
      a significant role in the elimination of droloxifene. An unusual diglucuronide of
      4-hydroxydroloxifene was also identified in this species. 5. In rat,
      glucuronidation and oxidative metabolism were significant, whereas in monkey
      glucuronidation of droloxifene was the predominant pathway of elimination.

PMID- 9522441
TI  - Metabolism of a novel CCK-B antagonist in rat, dog and human liver microsomes.
AB  - 1. The in vitro metabolism of a novel CCK-B antagonist ((+)-N-[1-adamantane-1
      methyl)-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-1H- 1, 5-benzodiazepin-3-yl]N'
      phenyl-urea; GV150013X) was investigated using rat, dog and human liver
      microsomes. 2. Four monohydroxy and four dihydroxy metabolites of GV150013X in
      rat and man were identified by comparison with authentic standards using HPLC and
      mass spectrometry. 3. The dihydroxy metabolite M1 was not detected in dog liver
      microsomes mixtures. 4. The formation of dihydroxylated metabolites proceeds via
      monohydroxylated metabolites M5 and M8 and not directly from GV150013X. 5. A
      monohydroxy metabolite M5 was the major metabolite in rat and dog, with M5 and
      dihydroxy metabolites M2 and M3 major metabolites in man.

PMID- 9522442
TI  - Absorption, distribution, metabolism and excretion of 14C-labelled enantiomers of
      the calcium channel blocker benidipine after oral administration to rat.
AB  - 1. Each of the 14C-labelled optical isomers of benidipine, a new calcium
      antagonist, was separately administered orally to the male rat at a dose of 0.5
      or 1 mg/kg. The absorption, distribution, metabolism and excretion of the 14C
      labelled optical isomers were investigated. 2. Plasma concentrations of
      radioactivity after administration of the (-)-alpha isomer were higher than those
      after administration of the (+)-alpha isomer. 3. The highest radioactivity was
      found in liver and high levels of radioactivity were found in the kidney, adrenal
      gland and lung after administration of the (+)- or (-)-alpha isomers of
      benidipine. Up to 72 h, the tissue concentration of radioactivity fell from 1.4
      to 9.2% of the highest level in each tissue for the (+)-alpha isomer and from 1.8
      to 13.0% for the (-)-alpha isomer. 4. The ratios of the area under the time-curve
      of each tissue concentration to that of the corresponding plasma concentration
      were almost equal after the separate administrations of both isomers. 5. The
      dominant urinary and biliary metabolic pathways of the (+)-isomer were the
      hydrolysis of 1-benzyl 3-piperidylester followed by the oxidation of the
      dihydropyridine ring and N-dealkylation followed by hydrolysis of the
      methylester. Those of the (-)-isomer were the hydrolysis of 1-benzyl 3
      piperidylester followed by the oxidation of dihydropyridine ring and of the
      oxidation methyl group, N-dealkylation followed by hydrolysis of the methylester,
      decarboxylation and glucuronidation of the piperidyl moiety after the oxidation
      of the dihydropyridine ring. 6. The cumulative excretion of radioactivity in
      urine and faeces up to 72 h after administration of the (+)-alpha isomer was 8.8
      and 90.7% of the dose respectively. The corresponding values of the (-)-alpha
      isomer were 19.7 and 72.9% of the dose respectively. 7. The excretion of
      radioactivity in bile up to 48 h after administration of the (+)- and (-)-alpha
      isomer was 42.1 and 46.7% of the dose respectively.

PMID- 9522443
TI  - Metabolism of 2,2',4,4'-tetrabromodiphenyl ether in rat and mouse.
AB  - 1. The distribution and excretion of orally administered 14C-labelled 2,2',4,4'
      tetrabromodiphenyl ether (TBDE) have been studied in rat and mouse. 2. TBDE was
      efficiently absorbed and stored in adipose tissue where high concentrations were
      observed in both species. 3. In the rat, 86% of the dose was retained after 5
      days, while 14% was excreted via the faeces and < 0.5% via the urine. 4. The
      mouse excreted 20% of the dose via the faeces and 33% via the urine, the latter
      as a hydrophilic and labile metabolite. 5. Metabolites covalently bound to
      macromolecules and lipids were noted in tissues and faeces from both species. 6.
      The major individual compound was parent TBDE in the faeces and tissues although
      small amounts of five hydroxylated metabolites were indicated by GC-MS. 7. In
      plasma from both rat and mouse only a few of the hydroxylated metabolites were
      present, indicating selective retention of these metabolites.

PMID- 9522446
TI  - Binding of Escherichia coli verotoxins to cell surface protein on wild-type and
      globotriaosylceramide-deficient Vero cells.
AB  - We have examined verotoxin (VT) binding to cell surface proteins. When Vero or
      globotriaosylceramide (Gb3) deficient Vero (VRP) cells were incubated with 125I
      labelled verotoxin 2(VT2) and disuccinimidyl suberate cross-linker, SDS-PAGE of
      cell lysates showed radiolabelled bands at 44, 50, 60, 86, 102, and 138 kDa. When
      125I-labelled verotoxin 1 (VT1) was cross-linked, radioactive bands occurred at
      51, 67, 101, 160, 188, and 232 kDa. In contrast, 125I-labelled VT1 B subunit
      produced a single radioactive band migrating at 50 kDa. CHO cells did not bind
      labelled VT. VT2 binding to VRP cells fit a rectangular hyperbola suggesting a
      single class of binding sites. In contrast, VT1 and VT1 B subunit binding to VRP
      cells was best fit by sigmoidal curves suggesting the presence of positive
      cooperativity between at least two binding sites. Scatchard analysis of VT2
      binding data yielded 3.5 x 10(9) molecules bound/microgram of cell protein with
      an equilibrium dissociation constant (KD) of 13 nM. The apparent KD was 9.7nM for
      VT1 and 73.2 nM for VT1 B subunit. These results indicate that VT binds to a
      protein, or proteins, on the surface of susceptible cells and that there appear
      to be differences between VT1 and VT2 binding. Interactions between VT1 or VT2
      and the proteins demonstrated here may be important in the biological activity of
      VT.

PMID- 9522444
TI  - Effect of tea on the formation of DNA adducts by azoxymethane.
AB  - 1. The effect of black tea on the conversion of azoxymethane (AOM) to DNA
      reactive metabolites was studied in four groups of the male F344 rat. Each
      received 1.25% solutions of tea for 2 or 6 weeks, and simultaneous controls drank
      water. All rats were injected s.c. twice with 15 mg/kg AOM after the first or
      fifth week respectively, on tea or water, and again 1 week later. Groups were
      killed 6 h after the last dose, or 18 h later. The liver and colon were rapidly
      removed and rinsed with buffer solution, pH 7.0. DNA was isolated from these
      tissues, and DNA methylation was examined by the typical fluorescence of 06
      methylated and N-7-methylated products, separated by HPLC. 2. Two or 6 weeks of
      tea intake failed to affect significantly the formation of alkylated DNA from
      liver and colon compared with controls drinking water. Only in the group of rats
      on tea for 6 weeks, and killed 6 h after the last dose of AOM, was the O6
      methyldG and 7-methyldG decreased in DNA obtained from colon. 3. Thus, solutions
      of tea affected the formation of alkylated products in DNA of the colon of rats
      given AOM only at one time point, but did not do so under most other experimental
      conditions. The underlying mechanism is based on our previous finding that tea
      does not affect cytochrome P4502E1 that our group established to be the enzyme
      metabolizing AOM.

PMID- 9522447
TI  - Quantification of poliovirus in seawater and sewage by competitive reverse
      transcriptase--polymerase chain reaction.
AB  - Reverse transcriptase-polymerase chain reaction (RT-PCR) has been used
      extensively to detect enteric viruses in environmental samples. Advantages of RT
      PCR include its high detection sensitivity and rapid turn-around time. However,
      unlike traditional cell culture, RT-PCR has not provided quantitation and
      infectivity information. In this study, we have developed a quantitative RT-PCR
      method that can be used to determine the amount of poliovirus RNA in
      environmental samples. An RNA internal standard for poliovirus RT-PCR was
      designed and obtained through genetic engineering. Serial dilutions of RNA
      internal standard templates were amplified with a 5'-carboxyfluorescein-labeled
      poliovirus downstream primer and a nonlabeled poliovirus upstream primer in the
      RT-PCR. The fluorescent light intensity of labeled RT-PCR products was quantified
      using an ABI DNA sequencer with GeneScan software. The internal standard was
      coamplified with poliovirus in the RT-PCR, allowing for enumeration of the
      poliovirus RNA present in the seawater and sewage samples. This method, using a
      cloned internal standard and specified primers in the PCR, may be applied to
      quantify other microorganisms in environmental samples. Although quantitative RT
      PCR has begun to be used more extensively for detecting pathogens in clinical
      samples, the complex nature of many environmental samples has limited the sample
      range of the effectiveness of quantitative RT-PCR.

PMID- 9522448
TI  - Biphenyl-associated meta-cleavage dioxygenases from Comamonas testosteroni B-356.
AB  - In addition to 2,3-dihydroxybiphenyl 1,2-dioxygenase (B1,2O), biphenyl-grown
      cells of Comamonas testosteroni B-356 were shown to produce a catechol 2,3
      dioxygenase (C2,3O). B1,2O showed strong sequence homology with B1,2Os found in
      other biphenyl catabolic pathways, while partial sequence analysis of the C2,3O
      of B-356 suggested a relationship with xylEII-encoded C2,3O. The coexistence of
      two meta-cleavage dioxygenases in this strain prompted a comparison between the
      catalytic properties of the two enzymes. C2,3O has a much broader substrate
      specificity than native or His-tagged B1,2O: both enzymes were inhibited by
      chlorocatechols, but B1,2O was more sensitive than C2,3O. The results are
      discussed in terms of the physiological implications of interaction between
      metabolites from the lower biphenyl-chlorobiphenyl pathway and enzymes of the
      upper pathway.

PMID- 9522449
TI  - Developmentally regulated protein synthesis during intraperiplasmic growth of
      Bdellovibrio bacteriovorus 109J.
AB  - Bdellovibrio bacteriovorus 109J is an obligate intraperiplasmic predator of other
      Gram-negative bacteria. Collision with a suitable prey cell initiates a
      developmental sequence ultimately resulting in the destruction of the prey cell
      and the production of progeny bdellovibrios. Two-dimensional gel analysis of
      patterns of protein synthesis at various times in a synchronously growing culture
      of Bdellovibrio bacteriovorus 109J revealed over 30 polypeptides whose syntheses
      are developmentally regulated. The majority of these polypeptides fall into nine
      categories: attack phase specific or one of eight different kinetic groups
      expressed during the intraperiplasmic growth phase. The results indicate that
      Bdellovibrio bacteriovorus 109J has a complex system for regulating gene
      expression during its developmental cycle.

PMID- 9522450
TI  - Sequencing of porA from clinical isolates of Neisseria meningitidis defines a
      subtyping scheme and its genetic regulation.
AB  - Subtyping Neisseria meningitidis by methods that rely on monoclonal antibody
      (mAb) reactivity results in an unusually high number of strains that are not
      subtypeable. To subtype 48 strains isolated (1993-1994) in the province of Quebec
      that were not subtypeable by mAb-based techniques, we used DNA sequencing of the
      variable regions of porA, a gene that encodes the class 1 outer membrane protein.
      We assigned subtypes to all the previously nonserosubtypeable isolates and
      identified some novel subtypes. Because our sequencing strategy included the
      promoter region of porA, different isolates were compared in their sequences of
      the porA promoter region. A poly(G) stretch lies between the -10 and -35 regions
      of the promoter; replacement of a G residue by an A residue in this region
      resulted in loss of expression of porA. No correlation was found between the
      number of G residues in the poly(G) stretch and the level of expression; a
      minimum of 10 G residues is required in this stretch for expression of porA. One
      isolate expressed no class 1 outer membrane protein because of the insertion
      sequence IS1301 in the coding region of porA. Another isolate did not express the
      protein owing to a frame-shift mutation within the coding region of porA.
      Sequencing of porA allowed assignments of subtypes to previously uncharacterized
      isolates and provided insights about the regulation of expression of this gene in
      N. meningitidis.

PMID- 9522452
TI  - In vitro antifungal activity of some Mannich bases of conjugated styryl ketones.
AB  - Four Mannich bases of some conjugated styryl ketones IIa-IId were examined for
      antifungal activity. These compounds were designed as thiol-alkylators and had
      two centers for attack by cellular thiols. The most potent compounds IIa and IIb
      possessed hydrophobic, electron-attracting substituents in the aryl rings and in
      general had minimum inhibitory concentration (MIC) values of 0.2-25 microM
      against a variety of fungi. None of the four compounds inhibited the growth of a
      number of bacteria (MIC > 100 microM). The minimum fungicidal concentration (MFC)
      values for IIa and IIb were generally either similar or twofold higher than the
      MIC figures for fungi. Compound IIa demonstrated rapid, concentration-dependent
      inhibition of the growth of Candida albicans B311. The toxicity of IIa to normal
      human cells was much lower than the concentrations of this compound required to
      inhibit fungal growth. In summary, this study of four prototypic molecules has
      revealed that this class of compounds may have potential for further development
      as candidate antifungal agents.

PMID- 9522453
TI  - Functional characterization of the Haemophilus influenzae 4.5S RNA.
AB  - The putative 4.5S RNA of Haemophilus influenzae was identified in the genome by
      computer analysis, amplified by the polymerase chain reaction, and cloned. We
      have determined that this putative 4.5S RNA will complement an Escherichia coli
      strain conditionally defective in 4.5S RNA production. The predicted secondary
      structures of the molecules were quite similar, but Northern analysis showed that
      the H. influenzae RNA was slightly larger than the E. coli RNA. The H. influenzae
      gene encoding this RNA is the functional homolog of the ffs gene in E. coli.

PMID- 9522454
TI  - The division apparatus of plastids and mitochondria.
AB  - Mitochondria and plastids in eukaryotic cells contain distinct genomes and
      multiply in the cytoplasm by binary division of preexisting organelles.
      Mitochondrial and plastid nuclei are easily visualized as compartments in the
      matrix of organelles by high-resolution fluorescence microscopy and by
      immunoelectron microscopy using anti-DNA antibodies. Plastid and mitochondrial
      division can be clearly separated into two main events: division of the organelle
      nuclei, and then division of the rest of the organelles, the process of
      organellokinesis (mitochondriokinesis and plastidokinesis). The mechanical
      apparatus that regulates organellokinesis has remained undetermined. In 1986, the
      plastid-dividing apparatus (PD ring) for plastidokinesis was first identified by
      us in the primitive red alga Cyanidium caldarium RK-1. The PD ring is located in
      the cytoplasm outside the organelle envelope at the constricted isthmus of
      dividing organelles and has subsequently been found in all eukaryotic plants
      examined. We were also the first to identify the mitochondrion-dividing apparatus
      (MD ring) for mitochondriokinesis in the unicellular red alga Cyanidioschyzon
      merolae in 1993. Eukaryotic cell division is therefore controlled by at least
      three dividing apparata (rings), a contractile ring, an MD ring, and a PD ring,
      while bacterial division is controlled by a single bacterial contractile FtsZ
      ring. The aims of this review are to present the fine structure, process of
      formation, and contraction of the organelle-dividing apparatus, focusing on
      evolutionary conservation and diversion from the bacterial contractile ring.

PMID- 9522455
TI  - Nuclear and cytoplasmic glycosylation.
AB  - O-GlcNAcylation is a form of cytoplasmic and nuclear glycosylation that is found
      on many diverse proteins of the cell including RNA polymerase II and its
      associated transcription factors, cytoskeletal proteins, nucleoporins, viral
      proteins, heat shock proteins, tumor suppressors, and oncogenes. It involves the
      attachment of a single, unmodified N-acetylglucosaminyl residue O-glycosidically
      linked to the hydroxyl groups of serine and threonine moieties of proteins. It is
      a highly abundant and dynamic form of posttranslational modification that appears
      to modulate function in a manner similar to phosphorylation. All O-GlcNAc
      containing proteins are phosphoproteins that are involved in the formation of
      multimeric complexes, suggesting that O-GlcNAc may play a role in mediating
      protein-protein interactions. O-GlcNAc sites resemble phosphorylation sites and
      in many cases the two modifications are mutually exclusive; therefore, O
      GlcNAcylation may act as an antagonist of phosphorylation and help to mediate
      many essential functions of the cell.

PMID- 9522456
TI  - Microtubule-organizing centers and nucleating sites in land plants.
AB  - Microtubule-organizing centers (MTOCs) are morphologically diverse cellular sites
      involved in the nucleation and organization of microtubules (MTs). These
      structures are synonymous with the centrosome in mammalian cells. In most land
      plant cells, however, no such structures are observed and some have argued that
      plant cells may not have MTOCs. This review summarizes a number of experimental
      approaches toward the elucidation of those subcellular sites involved in
      microtubule nucleation and organization. In lower land plants, structurally well
      defined MTOCs are present, such as the blepharoplast, multilayered structure, and
      polar organizer. In higher plants, much of the nucleation and organization of MTs
      occurs on the nuclear envelope or other endomembranes, such as the plasmalemma
      and smooth (tubular) endoplasmic reticulum. In some instances, one endomembrane
      may serve as a site of nucleation whereas others serve as the site of
      organization. Structural and motor microtubule-associated proteins also appear to
      be involved in MT nucleation and organization. Immunochemical evidence indicates
      that at least several of the proteins found in mammalian centrosomes, gamma
      tubulin, centrin, pericentrin, and polypeptides recognized by the monoclonal
      antibodies MPM-2, 6C6, and C9 also recognize putative lower land plant MTOCs,
      indicating shared mechanisms of nucleation/organization in plants and animals.
      The most recent data from tubulin incorporation in vivo, mutants with altered MT
      organization, and molecular studies indicate the potential of these research
      tools in investigation of MTOCs in plants.

PMID- 9522457
TI  - The Wilms' tumor 1 gene: oncogene or tumor suppressor gene?
AB  - The Wilms' tumor 1 (wt1) gene is one of at least three genes that are involved in
      the development of Wilms' tumor, a pediatric kidney cancer. The expression
      pattern of the gene indicates that wt1 not only plays a role during kidney
      development but is also involved in the development and homeostasis of several
      other tissues. The physiological function of the gene, however, remains to be
      elucidated. The gene products have been implicated in many processes like
      proliferation, differentiation, and programmed cell death (apoptosis). The WT1
      proteins function as transcription factors but may additionally be involved in
      splicing. Disruption of these activities may lead to aberrant development. In
      this paper we will discuss the role of the wt1 gene during normal development and
      homeostasis of several tissues. In addition, we will address the involvement of
      the gene products in processes like apoptosis and tumorigenesis.

PMID- 9522458
TI  - Exocytosis in chromaffin cells of the adrenal medulla.
AB  - The chromaffin cell has been used as a model to characterize releasable
      components present in secretory granules and to understand the cellular
      mechanisms involved in catecholamine release. Recent physiological and
      biochemical developments have revealed that molecular mechanisms implicated in
      granule trafficking are conserved in all eukaryotic species: a rise in
      intracellular calcium triggers regulated exocytosis, and highly conserved
      proteins are essential elements which interact with each other to form a
      molecular scaffolding, ensuring the docking of granules at the plasma membrane,
      and perhaps membrane fusion. However, the mechanisms regulating secretion are
      multiple and cell specific. They operate at different steps along the life of a
      granule, from the time of granule biosynthesis up to the last step of exocytosis.
      With regard to cell specificity, noradrenaline and adrenaline chromaffin cells
      display different receptor and signaling characteristics that may be important to
      exocytosis. Characterization of regulated exocytosis in chromaffin cells provides
      not only fundamental knowledge of neurosecretion but is of additional importance
      as these cells are used for therapeutic purposes.

PMID- 9522459
TI  - The role of the dynactin complex in intracellular motility.
AB  - Dynactin is a multisubunit complex that binds to the minus-end-directed
      microtubule motor cytoplasmic dynein and may provide a link between the motor and
      its cargo. Results from genetic studies in Saccharomyces cerevisiae, Neurospora
      crassa, Aspergillus nidulans, and Drosophila have suggested that cytoplasmic
      dynein and dynactin function in the same cellular pathways. p150Glued, a
      vertebrate homologue of the Drosophila gene Glued, is the largest polypeptide in
      the dynactin complex with multiple protein interactions. Centractin, the most
      abundant dynactin subunit polypeptide, forms an actin-like filament at the base
      of the complex. Studies on dynamitin, the 50-kDa dynactin subunit, predict a role
      for dynactin in mitotic spindle assembly. Other subunits of dynactin have also
      been cloned and characterized; these studies have provided insight into the role
      of the complex in essential cellular processes.

PMID- 9522460
TI  - Dual mechanisms of apoptosis induction by cytotoxic lymphocytes.
AB  - Cytotoxic T lymphocytes and natural killer cells together comprise the means by
      which the immune system detects and rids higher organisms of virus-infected or
      transformed cells. Although differing considerably in the way they detect foreign
      or mutated antigens, these cells utilize highly analogous mechanisms for inducing
      target cell death. Both types of effector lymphocytes utilize two principal
      contact-dependent cytolytic mechanisms. The first of these, the granule
      exocytosis mechanism, depends on the synergy of a calcium-dependent pore-forming
      protein, perforin, and a battery of proteases (granzymes), and it results in
      penetration by effector molecules into the target cell cytoplasm and nucleus. The
      second, which requires binding of FasL (CD95L) on the effector cell with trimeric
      Fas (CD95) molecules on receptive target cells, is calcium independent and
      functions by generating a death signal at the inner leaflet of the target cell
      membrane. Exciting recent developments have indicated that both cytolytic
      mechanisms impinge on an endogenous signaling pathway that is strongly conserved
      in species as diverse as helminths and humans and dictates the death or survival
      of all cells.

PMID- 9522461
TI  - Drought-induced responses in plant cells.
AB  - Plants subjected to water stress undergo numerous physiological and metabolic
      changes. A general decrease in photosynthetic rate is among the most common
      responses. This is due to a programmed process involving the closure of stomata
      and reduction in the activity of photosynthetic enzymes. The plant hormone
      abscisic acid plays an important role in this process. Accumulation of compatible
      solutes, during water stress, is thought to be an adaptive response which has
      been developed by some plant species. Engineering the genes involved in the
      synthesis of these compounds, into nonaccumulating plants, has demonstrated
      promising results for genetic improvement of drought tolerance. Drought stress
      induces alteration of gene expression. A large number of genes which are
      upregulated by water stress have been isolated and characterized. Proteins
      encoded by some of these genes share several characteristics. The biochemical
      role of most of these gene products is unknown, but potential adaptive functions
      have been suggested. Abscisic acid is involved in the regulation of some of these
      genes.

PMID- 9522462
TI  - Peptidergic control of the corpus cardiacum-corpora allata complex of locusts.
AB  - The brain-corpora cardiaca-corpora allata complex of insects is the physiological
      equivalent of the brain-hypophysis axis of vertebrates. In locusts there is only
      one corpus cardiacum as a result of fusion, while most other insect species have
      a pair of such glands. Like the pituitary of vertebrates, the corpus cardiacum
      consists of a glandular lobe and a neurohemal lobe. The glandular lobe
      synthesizes and releases adipokinetic hormones. In the neurohemal part many
      peptide hormones, which are produced in neurosecretory cells in the brain, are
      released into the hemolymph. The corpora allata, which have no counterpart in
      vertebrates, synthesize and release juvenile hormones. The control of the locust
      corpus cardiacum-corpora allata complex appears to be very complex. Numerous
      brain factors have been reported to have an effect on biosynthesis and release of
      juvenile hormone or adipokinetic hormone. Many neuropeptides are present in
      nerves projecting from the brain into the corpora cardiaca-corpora allata
      complex, the most important ones being neuroparsins, ovary maturating parsin,
      insulin-related peptide, diuretic peptide, tachykinins, FLRFamides, FXPRLamides,
      accessory gland myotropin I, crustacean cardioactive peptide, and schistostatins.
      In this paper, the cellular distribution, posttranslational processing, peptide
      receptor interaction, and inactivation of these peptides are reviewed. In
      addition, the signal transduction pathways in the release of adipokinetic hormone
      and juvenile hormone from, respectively, the corpora cardiaca and corpora allata
      are discussed.

PMID- 9522463
TI  - The expression of an abscisic acid-responsive glycine-rich protein coincides with
      the level of seed dormancy in Fagus sylvatica.
AB  - By differential screening of a cDNA library constructed from poly (A+) RNA of ABA
      treated seeds of Fagus sylvatica L., we have isolated an ABA-responsive clone
      that is present in dormant seeds and under conditions that maintain dormancy, but
      it tends to disappear under conditions breaking seed dormancy. A search of the
      sequence data bases showed that the clone codes for a Glycine-Rich Protein and
      has sequence similarity to RNA-binding proteins. The clone, which exibits the
      characteristics of lea-genes, is up-regulated by ABA and down-regulated by GA3.
      Paclobutrazol abolishes the effect of GA3, which is restored upon addition of
      GA3. The possible relationship of this Glycine-Rich Protein to seed dormancy in
      F. sylvatica is discussed.

PMID- 9522464
TI  - The chloroplast-located homolog of bacterial DNA recombinase.
AB  - The cDNA for the chloroplast-located homolog of bacterial RecA protein,
      designated recA-AT, was placed in a plasmid appropriate for in vitro
      transcription and translation. Translation with 35S-labeled Met permitted
      demonstration of uptake of the protein product into isolated pea chloroplasts,
      and processing to a mature size. Preliminary evidence for the first amino acid
      was estimated from results using both 35S-Met and 3H-Leu for in vitro
      transcription and translation, followed by uptake into chloroplasts and
      processing. The labeled protein was subject to sequential amino acid hydrolyses,
      and radioactivity was measured in each round. Induction of gene transcription in
      leaves infiltrated with the DNA-damaging agent, methyl methane-sulfonate was
      shown by Northern blot analysis. Further constructs were made for over-expression
      of the gene in E. coli; and one out of many tried permitted production of some
      soluble protein. Extracts from transformed bacteria were shown to have RecA
      activity using the "POM" assay [Bertrand et al. (1993) Nucl. Acids Res. 21:3653]
      for DNA strand transfer. The protein was purified to close to homogeneity using
      methods developed for E. coli RecA isolation.

PMID- 9522465
TI  - The expression of an aquaporin promoter from Mesembryanthemum crystallinum in
      tobacco.
AB  - The promoter region of the MipB gene encoding an aquaporin from Mesembryanthemum
      crystallinum was isolated and used in a transcriptional fusion to control uidA
      expression in tobacco. The sequence of the promoter was determined for 2 kb
      upstream of the translation initiation site. Three start sites were utilized with
      approximately equal frequency, located 176, 170, and 161 bases, respectively,
      upstream of the translation initiation site. As judged by analysis of GUS
      expression, promoter MipB retains its specificity in transgenic tobacco. In
      germinating seedlings, all cells showed GUS expression of different intensities
      with the strongest signals in root meristems. In older seedlings, GUS staining
      was observed in rapidly expanding cells--root and apical meristem, and lateral
      root primordia. In mature plants, strong GUS activity was located to glandular
      trichomes, subepidermal cells of the stem and petioles, to cells surrounding
      vascular tissues as well as in xylem parenchyma cells. In immature floral organs,
      GUS expression was strong in sepals, petals, stamen, and pistil. The intensity
      declined as they matured. In general, this promoter was active in rapidly
      expanding cells and cells with high water flux capacity, especially in the xylem
      parenchyma.

PMID- 9522466
TI  - Effects of site-directed mutagenesis of conserved Lys606 residue on catalytic and
      regulatory functions of maize C4-form phosphoenolpyruvate carboxylase.
AB  - Lys606, one of the two highly conserved lysine residues in maize C4-form
      phosphoenolpyruvate carboxylase (PEPC), was converted to Asn, Glu or Arg by site
      directed mutagenesis. Resulted mutant enzymes expressed using pET system [Dong,
      L.-Y. et al. (1997) Biosci. Biotech, Biochem. 61:545] were purified by one step
      procedure through nickel-chelate affinity chromatography to a purity of about
      95%. The replacement of Lys606 by Arg had little effect on the kinetic and
      allosteric properties of the resulting mutant enzyme. In contrast, the maximum
      velocities (Vmax) were decreased to 22% and 2% of that of wild-type PEPC upon the
      substitution of Lys606 by Asn and Glu, respectively. The value of S0.5(HCO3-) was
      increased 21-25 fold by the replacements, whereas the S0.5(Mg2+) and S0.5(PEP)
      values were increased only 5-8 fold. The extents of activation of mutant enzymes
      by glucose 6-phosphate and glycine were 2 to 3-fold higher than those of wild
      type enzyme. The mutant enzymes showed less sensitivity to malate inhibition,
      compared with the wild-type enzyme. The results suggested that the Lys606 is not
      obligatory for the enzyme activity, but may be involved in the bicarbonate
      binding and contribute somehow to the allosteric regulatory properties.

PMID- 9522467
TI  - Changes in soluble sugar, starch, and alcohol dehydrogenase in Arabidopsis
      thaliana exposed to N2 diluted atmospheres.
AB  - Proper exchange of atmospheric gases is important for normal root and shoot
      metabolism in plants. This study was conducted to determine how restricted air
      supply affects foliar carbohydrates, while using the marker enzyme alcohol
      dehydrogenase (ADH) to report on the oxygenation status of the rootzone. Fourteen
      day-old Arabidopsis thaliana (L.) Heynh. plants grown singly in 7-ml tubes
      containing agarified nutrient medium were placed in coupled Magenta vessels and
      exposed for six days to either ambient air or one of six different air/nitrogen
      dilutions. Redox potential of the agar medium was measured immediately after
      harvesting and freezing leaf tissue, and then root systems were quickly extracted
      from the agar and frozen for subsequent analyses. Redox potential measurements
      indicated that this series of gas mixtures produced a transition from hypoxia to
      anoxia in the root zones. Root ADH activity increased at higher rates as the
      redox potential neared anoxic levels. In contrast, ADH mRNA expression quickly
      neared its maximum as the medium became hypoxic and showed little further
      increase as it became anoxic. Foliar carbohydrate levels increased 1.5- to 2-fold
      with decreased availability of metabolic gases, with starch increasing at higher
      concentrations of air than soluble carbohydrate. The results serve as a model for
      plant performance under microgravity conditions, where absence of convective air
      movement prevents replenishment of metabolic gases.

PMID- 9522469
TI  - cDNA cloning and tissue specific expression of a gene for sucrose transporter
      from rice (Oryza sativa L.).
AB  - We describe the cloning and expression analysis of a sucrose transporter cDNA
      from a monocot (the rice plant, Oryza sativa L.). The cDNA clone (OsSUT1) encoded
      an open reading frame of 1,611 bp (537 amino acids) and showed 76.8 to 79.7%
      similarity at the amino acid level to other sucrose transporters of dicot
      species. The predicted membrane topology of OsSUT1 protein is made up of 12
      transmembrane helices which is consistent with most of the mono- and disaccharide
      transporters previously identified. When OsSUT1 cDNA was introduced into yeast
      and expressed, the cells rapidly accumulated sucrose demonstrating that OsSUT1
      does, in fact, encode a sucrose transporter. From genomic Southern hybridization
      OsSUT1 appeared to be a single copy gene. OsSUT1 was expressed in source organs
      such as leaf blade, leaf sheath and germinating seed whereas little or no
      expression was observed in some sink organs such as the panicles before heading
      and the roots. Transcript was observed at high levels in panicles after heading,
      particularly in the portion containing endosperm and embryo. In addition,
      expression of OsSUT1 was high in etiolated seedlings and decreased during light
      induced greening.

PMID- 9522468
TI  - Expression of the plastid ndhF gene product in photosynthetic and non
      photosynthetic tissues of developing barley seedlings.
AB  - A fragment of the NDH-F subunit of the plastid NAD(P)H dehydrogenase complex
      (NAD(P)H-plastoquinone-oxidoreductase) from barley was expressed as a fusion
      protein in Escherichia coli and an antibody to the fusion protein was prepared.
      Western blot analysis using the anti-NDH-F antibody showed specificity towards a
      plastid polypeptide of approximately 70 kDa present in both photosynthetic and
      non-photosynthetic barley tissue. The polypeptide was found in thylakoid
      membranes of green leaves whereas in etiolated leaves it was shown to be
      associated with the membrane fraction of etioplasts. NDH-F levels were higher in
      roots and etiolated tissue than in greening or young leaves. During leaf
      ontogeny, NDH-F levels decreased from young to mature tissue but increased during
      senescence. The accumulation of NDH-F in thylakoids of young leaves was
      stimulated by photooxidative treatment. The results indicate a high degree of
      expression of plastid ndh genes (which encode NAD(P)H dehydrogenase subunits) in
      non-photosynthetic plastids and under conditions which impair the photosynthetic
      activity of chloroplasts. In addition to its putative implication in
      photosynthetic electron transport, a non-photosynthetic role, such as
      chlororespiration, is proposed for the plastid NAD(P)H dehydrogenase complex.

PMID- 9522470
TI  - Spatial patterns of phytochrome expression in young leaves of the fern Adiantum
      capillus-veneris.
AB  - The spatial distribution of phytochrome (PHY1) mRNA in the fern Adiantum was
      investigated by in situ hybridization. PHY1 mRNAs are expressed predominantly in
      the abaxial rather than the adaxial part of the petiole of leaf croziers.
      Moreover, the signals in light-grown croziers are predominantly nuclear in
      location rather than cytoplasmic.

PMID- 9522471
TI  - cDNA cloning of squalene synthase genes from mono- and dicotyledonous plants, and
      expression of the gene in rice.
AB  - cDNA clones encoding squalene synthases were isolated from rice, maize and
      soybeans. A phylogenetic tree showed that the enzymes of monocots and dicots form
      distinct subgroups. In rice, squalene synthase mRNA was detected in tissues
      containing dividing cells and its level was repressed by illumination.

PMID- 9522472
TI  - A pumpkin 72-kDa membrane protein of precursor-accumulating vesicles has
      characteristics of a vacuolar sorting receptor.
AB  - Precursor-accumulating (PAC) vesicles were previously shown to mediate the
      transport of the precursor of a major storage protein (pro2S albumin) to protein
      storage vacuoles in developing pumpkin cotyledons. In this study, we
      characterized two homologous proteins from PAC vesicles, a 72 kDa protein (PV72)
      and an 82 kDa protein (PV82). PV72 and PV82 showed an ability to bind to peptides
      derived from both an internal propeptide and a C-terminal peptide of pro2S
      albumin. PV72 was predicted to be a type I integral membrane protein with
      epidermal growth factor (EGF)-like motifs. These results suggest that PV72 and
      PV82 are potential sorting receptors for 2S albumin to protein-storage vacuoles.

PMID- 9522473
TI  - Integrated access to genomic and other bioinformation: an essential ingredient of
      the drug discovery process.
AB  - Due to the high rate of data production and the need of researchers to have rapid
      access to new data, public databases have become the major medium through which
      genome mapping and sequencing data as well as macromolecular structural data are
      published. There are now more than 250 databases of biomolecular, structural,
      genetic, or phenotypic data, many of which are doubling in size annually. These
      databases, many of which were created and are maintained by experimentalists for
      their own research use, provide valuable collections of organized, validated
      data. However, the very number and diversity of databases now make efficient data
      resource discovery as important as effective data resource use. Existing
      autonomous biological databases contain related data which are more valuable when
      interconnected than when isolated. Political and scientific realities dictate
      that these databases will be built by different teams, in different locations,
      for different purposes, and using different data models and supporting DBMSs. As
      a consequence, connecting the related data they contain is not straightforward.
      Experience with existing biological databases indicates that it is possible to
      form useful queries across these databases, but that doing so usually requires
      expertise in the semantic structure of each source database. Advancing to the
      next level of integration among biological information resources poses
      significant technical and sociological challenges.

PMID- 9522474
TI  - Data management in olfaction studies.
AB  - Problems arising in the collection of data in olfaction studies are discussed in
      relation with the specific nature of perception and description of odors.
      Olfactory data depend strongly on individual physiological differences, on
      measurement methods and on psychological factors. Classifications of odors are
      necessary to put some order in odor descriptions which are used in structure-odor
      relationships. Published classifications have been based on empirical, semi
      empirical, or statistical approaches. In the last category data may be obtained
      using semantic descriptions, or profiles, or similarity estimations. Examples of
      each kind of classification are presented and discussed. The intensity data are
      most often threshold data. They also present a huge variability which makes it
      difficult to relate them to physicochemical properties. Data on thresholds and
      attempts to standardize them are presented and discussed.

PMID- 9522475
TI  - Comparison of benzodiazepine-like compounds using topological analysis and
      genetic algorithms.
AB  - Four compounds within a set of ligands for the benzodiazepine receptors are
      characterized by their electron density maps at different resolution levels and
      reconstructed from calculated structure factors. The resulting complex three
      dimensional density maps are first simplified into connected graphs using
      topological analysis. Then, an original genetic algorithm method, GAGS (Genetic
      Algorithm for Graph Similarity search), is developed and implemented in order to
      compare the connected graphs. Finally, the analysis of the best solutions of the
      algorithm are expressed in terms of functional group superimpositions. The GAGS
      analysis is applied to different resolution levels of the electron density maps
      and the resulting models are compared in order to assess the influence of the
      resolution on the resulting pharmacophore models.

PMID- 9522476
TI  - Visualizing the future of molecular graphics.
AB  - The field of computer graphics has played an important role in the advancement of
      structural molecular biology and in the development of structure-based drug
      design. This article will provide a brief background on the development of this
      technology, and then focus on the current trends and future directions in
      molecular graphics and how they will impact the practice of molecular modeling
      and design. Specific areas that will be covered include: 1) the development of
      surface and volume based representations of molecular properties and
      interactions; 2) new approaches to modeling flexible and multi-component
      structures, and 3) the impact of object-oriented graphics-based programming and
      the rapidly growing use of network based computing.

PMID- 9522477
TI  - Automated docking and the search for HIV protease inhibitors.
AB  - This article will discuss the motivations, technologies, and future directions of
      computational automated docking in the context of the structure-based rational
      design of HIV-1 protease inhibitors. Docking simulations are widely used for
      screening of compound libraries to identify new drug leads, employing a simple
      model for rapid testing of thousands of compounds. Docking simulations are also
      useful for lead enhancement, using more detailed models to analyze the atomic
      interactions between inhibitors and target macromolecules. Major advances have
      been reported in the development of empirical force fields, which now allow
      assessment of relative binding strength and drug specificity, and extensions of
      automated docking techniques allow de novo drug design.

PMID- 9522479
TI  - [Current prospects in the community treatment of schizophrenia].
AB  - The advances of pharmacological and psychosocial therapies in recent years have
      deeply changed the perspectives on the treatment of schizophrenia in the
      community. The hospital-centred models are progressively being replaced with
      comprehensive community care models. After discussing the main aspects of this
      evolution at a conceptual level, the authors describe the currently available
      therapeutic interventions of schizophrenia in the community (pharmacological
      therapies, psychotherapies, psychosocial and family interventions) and their
      effectiveness. The authors also discuss the cost-effectiveness studies on the
      different models of treatment, namely those comparing the community-centred
      models with the more traditional ones. Finally, the organisational problems of
      the implementation of community-centred models are discussed and the perspectives
      in this field in our country are considered.

PMID- 9522480
TI  - Quality assurance in liaison psychiatry. European Consultation-Liaison Workgroup.
AB  - As far as we know, there is no experience of quality management in mental health
      care in Portugal. This study fills a gap in the area of consultation-liaison
      psychiatry. Due to its multidisciplinarity and to the complexity of the problems
      it deals with, consultation-liaison psychiatry seems a privileged field for the
      development of this kind of programme. The authors describe the different steps
      necessary for the implementation of a quality management study in one of the
      national centres and report some preliminary results that show the success it has
      attained.

PMID- 9522481
TI  - [Progress in psychoanalytic treatment].
AB  - The author considers psychoanalytic treatment to be most effective when based
      upon an interactive, intersubjective conception of normal and pathological
      psychic development. By internalizing pathological and pathogenic relationships
      during childhood, the person builds up a troubled internal relational pattern; it
      determines his her choices and ensuing relationships and thus perpetuates his her
      pathology. When it appears in the psychoanalytic relationship this pathological
      relational style can be analysed and resolved, while a new relationship, promoted
      by the psychoanalyst, is begun. It aims at fostering the person's development and
      mental health. This new, healthier relationship is progressively integrated into
      the patient's everyday life. Consequently the internal relationship pattern
      itself, through the person's new experiences, changes. Psychoanalysis comes to an
      end when the new internal relational pattern is consolidated. Therefore the
      psychoanalytic cure is seen as a process of transformation; and the psychoanalyst
      is its agent. Therein, the author maintains that counter transference precedes
      transference and is the driving force of the curing process. The author states
      that: precedence and priority should be given to counter-transference.

PMID- 9522482
TI  - [Psychosomatic syndromes in clinical practice. A proposal of diagnostic
      criteria].
AB  - The following is a translation of the proposed diagnostic criteria established by
      a European group for twelve common psychosomatic syndromes found in general
      clinical practice. Many of them have the potential to occur during different
      stages of a large variety of diseases and their detection could lead to better
      holistic provision of health care.

PMID- 9522483
TI  - [The applications of sleep studies in psychiatry].
AB  - In the last two decades considerable progress has been made in defining sleep
      changes in mental disorders, as well as in studying the relationship between
      sleep and psychiatric treatments. The pathophysiological significance of those
      changes has also been investigated, with some theoretical models of mental
      disorders indicating a direct role of sleep. In psychiatric research, sleep
      studies have contributed to the clarification of a variety of issues in relation
      to taxonomy, aetiology, pathogenesis and treatment. Furthermore, clinical and EEG
      aspects of sleep have proven useful for practical diagnostic and treatment
      purposes. This article aims to provide a systematic and critical review of
      current applications of sleep studies in psychiatry, both in research and
      clinical fields.

PMID- 9522485
TI  - [The consequences of drug use in adolescence].
AB  - This article is a overview of the multiple consequences of drug use, abuse and
      dependence among adolescents. Developmental issues on transition to adulthood are
      highlighted. The usual behavioural problems of drug addicts are explained on the
      basis of pathological defense mechanisms. A contemporary approach is made of the
      physical, psychological and social consequences of drug use.

PMID- 9522484
TI  - [Winter depression and phototherapy. The state of the art].
AB  - Winter depression (seasonal affective disorder, SAD) is characterised by a
      seasonal major depressive episode in the last 2 years. Hypersomnia, carbohydrate
      craving and weight-gain are specific traits. These patients preferentially seek
      help from their General Practitioner. Current research on the aetiology of SAD
      covers fields such as retinal deficiency, phase-disturbance of the internal
      circadian rhythms given by internal oscillators and neuro-endocrinologically
      expressed disorders, assuming that melatonin is the main mediator of human
      circadian systems in the CNS. Disorders of neurotransmitters (serotonin) are
      another cue. Recent longitudinal studies show a prevalence of seasonal depressive
      symptoms in up to 10% of the general population. Among patients treated for
      depression, the prevalence of SAD is even higher. The SAD sex-ratio of women to
      men of 3 to 1 is found repeatedly. SAD becomes rare above the age of 50.
      Effectiveness of phototherapy is showed in nearly all controlled studies. Bright
      light appears to be most effective for patients with mild SAD. Hypersomnia and
      hyperphagia seem to be predictors of response to bright light therapy. To enable
      evaluation of unspecific therapeutic factors in phototherapy a true placebo for
      bright light-studies is still to be found. Possible new indications for photo
      therapy are currently being explored. Bright light for non- seasonal depression
      has been tested with encouraging results; panic disorders seem to have features
      in common with SAD; effectiveness in bulimia has been suggested and recently
      sleep disorders in elderly patients have been successfully and substantially
      diminished.

PMID- 9522486
TI  - [The influence of sociodemographic and familial factors on the therapeutic
      evolution of heroin addicts in a program of staged combined treatment].
AB  - In this study the authors evaluate the history of drug abuse, the familial and
      sociodemographic influence on the clinical evolution of 74 heroin-addicts,
      admitted sequentially to a therapeutic drug-free program named Sequential
      Combined Treatment (SCT), based on family and individual counselling, with a
      daily administration of naltrexone and with regular evaluation of drug
      abstinence, based on urinary analysis collected by family members. The enrollment
      rate recorded was 76%, and the participation rates during the course of the
      program were 88% after 3 months of administering the antagonist, 57% after 6
      months, 47% after 9 months and 46% at the end of the 12th month. The results
      showed that age and previous scholarship levels, as well as parental or marital
      conflicts were significant predictors of over the subjects' total participation
      time in the program. The heroin-addicts with higher levels of scholarship or with
      drug abuse problems with other family members had more relapses during the
      treatment. No differences were found in the clinical variables of the therapeutic
      evolution among drug-addicts belonging to nuclear or enlarged family structures
      and single-parent or reconstructed family structures, which suggests that
      Sequential Combined Treatment (SCT) seems to have sufficiently similar results
      independently of the type of family structure to which they belong.

PMID- 9522487
TI  - [The bases and indications for the staged combined treatment of heroin addicts as
      outpatients].
AB  - Combined and staged treatment is a new clinical methodology for the orientation
      of drug addiction cases within families. This methodology resorts to several
      techniques in a combined way, such as: family therapy and counselling; the use of
      psychopharmacology and opioide antagonists; as well as individual and group
      psycho-therapeutics. These are all linked to a personal psycho-social
      rehabilitation program. This treatment is based on family accessibility and
      therapeutic community programs. The authors review different contributions and
      the evolution of different therapeutic modalities. Finally they propose a list
      for inductions and another for the formal contra-indications for this kind of
      treatment.

PMID- 9522489
TI  - [Psychiatry and primary care. A liaison experience].
AB  - Psychiatric problems are common in general medical practice. This paper reviews
      information supporting the need to integrate psychiatry and general medical
      practice. The two year liaison between the psychiatric ward of Santa Maria
      Hospital and Sete Rios Medical Centre is described. A model of longitudinal case
      supervision analogous to that used in psychiatric residency training to provide
      knowledge and skills in mental health can respond to the needs of general
      practitioners.

PMID- 9522488
TI  - [The alcohol-dependent outpatient: a clinical typology].
AB  - The aim of this study was to construct a typology integrating sociodemographic,
      clinical and personality data of alcohol-dependent patients. We studied a
      consecutive population attending an alcohol-dependent outpatient psychiatric
      department, assessed by instruments that measured psychiatric,
      psychopathological, personality and sociodemographic characteristics of alcohol
      dependent patients. The factorial analysis allowed us to define three main
      expressions of alcoholism: physical, psychological and social. In the elicited
      typology, both physical and social appear mixed in their expression. The
      psychological expression is divided into two main categories: the alexithymic
      (with a depressive personal and family history) and the psychopathologic type
      (with actual depression and anxiety). This typology should allow us to correlate
      these types with neurophysiological and biochemical patterns and could be
      particularly useful in building an etiologic model of alcohol dependence which
      could contribute to a better prediction of prognosis and choice of the best
      therapeutic intervention.

PMID- 9522492
TI  - [Education in liaison psychiatry in the psychiatric internship].
AB  - The development of consultation-liaison psychiatry in Portuguese general
      hospitals raises the need for specific training to be included in the preparation
      of psychiatric trainees. In order to contribute to a better quality of liaison
      psychiatric training we propose guidelines for this training period. We describe
      the aims of a training period, the core curriculum, the structure of this
      training and provide a bibliography. We also propose a systematic evaluation
      profile for psychiatric trainees and supervisor.

PMID- 9522491
TI  - [Platelet serotonin as a biological marker of autism].
AB  - Platelet levels of serotonin were determined by a quantitative direct
      radioimmunoassay, in a group of autistic patients and a control group. Thirty six
      autistic patients (28 males and 8 females), all with severe mental retardation,
      and a group of 23 matched controls, were studied. The serotonin levels in
      autistic patients (mean +/- SD) (88.37 mmol/dl +/- 40.38) were significantly
      higher that in the control group (49.54 mmol/dl +/- 16.49). There were no
      significant differences in levels between the sexes and age groups among subjects
      in the patient and the control groups. We detected a hyperserotoninaemia in 70%
      of the autistic patients. We also discuss correlations between serotonin levels
      in our patients with known aetiologies and levels quoted in the literature and
      propose RIA to be used as a quick, easy and reliable method for the analysis of
      large numbers of samples.

PMID- 9522490
TI  - [Psychological disorders. A study of social support].
AB  - Many studies have shown that social support is related with psychological
      disorders and both are high consumers of health service resources. A study was
      carried out by the author to identify psychological disorder relationships with
      social support and how they change in presence or absence of life events. An
      inquiry by questionnaire was conducted among a stratified proportional by sex and
      random age sample of correctly registered patients in the Family Medicine Out
      Patients Clinic of Ajuda Health Centre, Lisbon. A prevalence of 38.2% was
      obtained with the mental health scale and is clearly greater than other
      applications on identical populations. The Psychological situation depends
      inversely on social support adequacy, crisis resources, contacts network and
      economic situation; it depends on quantity and availability, but not on quality
      and accessibility; it is independent of the occurrence of life events. Social
      support induces changes on mental state (direct effect), but one life events it
      only induces changes in mental state related with social support (indirect
      effect). Social support seems to induce a buffering effect on life events upon
      psychological changes, but this work cannot support this evidence.

PMID- 9522493
TI  - [Mental anorexia].
AB  - After a brief theoretical introduction on mental anorexia the authors present a
      clinical case with this pathology, a male patient, which is rare in this
      pathology, who had been admitted to the Psychiatric Department of S. Francisco
      Xavier Hospital in 1994. Firstly the authors present a brief chronological
      summary of the patient's history in order to focus on the insidious development
      of this pathological process with increasing severity. Secondly the essential
      features of the disease are explained for the clinical evaluation of this
      patient. Finally the therapeutic approach is presented, drafted in a
      multidisciplinary perspective.

PMID- 9522494
TI  - [Dermatitis artefacta].
AB  - We report a case of a 29-year-old man presenting skin ulcerations on both sides
      of the mandible. The diagnosis of dermatitis artefacta was based on the
      morphology and evolution of the lesions, on the patient's borderline personality,
      on the objects found in his possession, and a later admission of having an
      involvement in the aggravation of the lesions.

PMID- 9522495
TI  - [Acromegaly with the sleep apnea syndrome].
AB  - The authors present the clinical of a male patient aged 45 years whose main
      complaints were loud snoring and excessive daytime sleepiness. Polysomnographic
      study revealed a sleep obstructive apnea syndrome with an apnea/hypopnea index of
      86.5. After being treated with nasal continuous positive air pressure, (12 cm
      H2O), the apneas ended and sleep architecture was corrected. Physical examination
      also indicated the presence of an acromegaly, and therefore, the patient was
      subjected to endocrinological and cerebral imagiological studies; the diagnosis
      confirmed it as a predisposing factor to the sleep breathing disorder. A brief
      literature review about the incidence of sleep apnea syndrome in acromegaly is
      also made; the authors conclude that there is still the need for a systematic
      screening of sleep breathing disorders in acromegalic patients in order to
      optimise the treatment and prognosis of this disorders.

PMID- 9522496
TI  - [Transthoracic needle aspiration as a diagnostic method].

PMID- 9522497
TI  - [Transthoracic needle aspiration biopsy. The diagnostic accuracy of pulmonary
      lesions].
AB  - We performed 91 transthoracic functions, under fluoroscopy, sonographically or by
      computed tomography control, at Clinic Hospital in Valencia. The procedures was
      performed with Chiba needle 22 gauges while the cytopathologist was present.
      Maximum number of needle passes was four. Malignant diagnosis has been obtained
      in 64.8% of cases, in 12 patients a benign diagnosis was obtained and confirmed,
      13 cases were false negative and the specimen was insufficient for diagnosis in 7
      (5 of them lesions had a diameter less than 2 cm). The study showed 82% for
      sensitivity, 100% for specificity and 85% for accuracy. The punction was guided
      by fluoroscopy in 49 patients, by sonography in 6 and by computed tomography
      control in 36. The accuracy diagnosis for fluoroscopy guidance was 96%. The
      complications were 9 (9.9%): Two patients presented minor hemoptysis resolved
      spontaneously, 6 patients showed minor pneumothorax and one patient was treated a
      cause of a large pneumothorax. We concluded that transthoracic biopsy is a simple
      and save technique that can provide a high diagnosis accuracy in patients with
      pulmonary pathology.

PMID- 9522498
TI  - [Serum creatine kinase MM isoforms and lactate dehydrogenase isoenzymes in
      patients with non-traumatic acute rhabdomyolysis].
AB  - We studied lactate-dehydrogenase (LD) isoenzymes and creatinekinase MM (CKMM)
      isoforms MM1, MM2 and MM3, in the serum of 18 patients with nontraumatic acute
      rhabdomyolysis, to test the utility of these markers in the diagnosis and disease
      evolution. The isoenzymes were separated by electrophoresis on agarose gel and
      were quantified with a densitometer. We studied the correlation between CKMM
      isoforms calculating the MM3/MM1 ratio, establishing the reference values from
      control group of 36 healthy adults. MM3 and MM3/MM1 ratio values were
      significantly increased in patients with rhabdomyolysis (p < 0.001) and
      progressively decreased coinciding with signs of getting better, showing 10 days
      after similar values of control group. LD4 and LD5 isoenzymes were significantly
      increased (p < 0.001) keeping elevated until 8-10 days when they showed a
      significant decrease compared with admission values (p < 0.05) but keeping
      elevated respect to control (p < 0.01).

PMID- 9522499
TI  - [The use of mebendazole associated with inoxuprin in the treatment of
      Schistosomiasis haematobium].
AB  - A controlled clinic assay was realized with 217 students of Marracuene, Maputo
      province in Mozambique. They were positives to Schistosoma haematobium parasite
      and 204 of them were positives helmints too. We created two groups for study.
      Group I received Mebendazole as treatment and Group II received Mebendazole and
      Inoxuprin that is considered as immunomodulator. They were rechecked one and six
      month after received treatment and we comproved that any people in Group II
      resulted positive after six month of treatment. We can be suppose that inoxuprin
      act to increasing the FC expression spot in mastocytes, eosinophils and B
      leukocytes and produce an augment in the number of specific IgE. In other hand
      when the parasites number is reduced or eliminated by Mebendazole, is reduced too
      the neuropeptides concentration and diminish the blocked of IFN gamma excretion,
      in this form we can to explain the infection resistance in the ages that are
      reported.

PMID- 9522500
TI  - [Multiple osteonecrosis in a patient with chronic alcoholism].
AB  - The osteonecrosis is usually due to various precipitating circumstances or
      predisposing factors that quite often appear mixed, although it can also appear
      with no evident cause. In this report, we provide a case of multiple
      osteonecrosis caused by chronic alcoholism, we review the literature and go over
      the general characteristics of the aseptic necrosis.

PMID- 9522501
TI  - [Angiosarcoma of gingival presentation].
AB  - We present the case of a woman of 62 years old with changes history in the
      intestinal habit, weak, thing, anemia, violet injuries in the gums and hemoptysis
      of small quantity. After the various tests accomplishment of image and biopsy of
      the injuries gingival and of lymphadenopathy supraclavicular was demonstrated the
      existence of a angiosarcoma of high degree of malignity. This neoplasm is
      originated in the cells of vascular endothelium and constitutes 1% of all the
      sarcomas and solely 4% appear the the oral cavity. These tumors has a high
      mortality (superior to the 20%) to five years. Once diagnosed its manage must be
      aggressive in spite of its wrong therapeutic response.

PMID- 9522502
TI  - [Clinical and sociological reflections before death].
AB  - The objective of this paper was to determine wether the clinical and sociological
      factors are implicated on the social rejection against the death. This is an
      inmutable phenomenon it is also changing and it has historicity. On the western
      countries it has become a peculiar phenomenon the dying patients and the death
      has shifted from home to hospital. Death on the hospital has been deshumaniced.
      Also, the physical and social death are differentiated and social and historical
      factors and social attitude changer are analyzed.

PMID- 9522503
TI  - [Management of chronic obstructive pulmonary disease: is there really more
      consensus, or just more consensus statements?].
AB  - Advances in the knowledge of chronic obstructive pulmonary disease
      pathophysiology have introduced chantes in the treatment of this disease, that
      have been presented in several guidelines published at a national or
      supranational level. In this paper some of these changes are analysed, together
      with significant aspects of these guidelines and items that remain unclear.

PMID- 9522504
TI  - [Methimazole arthritis in Graves Basedow disease].

PMID- 9522505
TI  - [Splenic spontaneous rupture in primary spleen lymphoma].

PMID- 9522506
TI  - [Clarithromycin-carbamazepine interaction: neurological symptoms and
      hyponatremia].

PMID- 9522507
TI  - [Primary cutaneous amyloidosis and idiopathic thrombocytopenic purpura].

PMID- 9522508
TI  - [Primary HIV infection with esophageal candidiasis and acute toxoplasmosis].

PMID- 9522509
TI  - [Analysis of mortality at a regional hospital: is it an index of assistance
      quality?].

PMID- 9522510
TI  - [Abdominal and thoracic subcutaneous emphysema with retropneumoperitoneum and
      pneumomediastinum in a gut-perforated patient].

PMID- 9522513
TI  - [HIV viral load. Current situation and perspectives].

PMID- 9522512
TI  - [Benign tumors of the liver: how to recognize them and what to do].

PMID- 9522514
TI  - [Clinical and epidemiologic study of meningococcal meningitis in the health
      region of Santiago de Compostela (1990-1997)].
AB  - BACKGROUND: The aim of this study was to determine the clinico-epidemiologic
      characteristics of meningitis caused by Neisseria meningitidis. METHODS: A
      retrospective study was performed of the bacterial meningitis with LCR positive
      cultures for Neisseria meningitidis from January 1990 to 31 March, 1997. To
      calculate the rate of incidence data from the 1990 population census were used
      corresponding to a population of 465,786 inhabitants per year attended in our
      hospital. RESULTS: A growth was observed in the strains of N. meningitidis in 61
      LCR, representing 30% of all positive LCRs. Thirty-three strains belonged to
      serogroup B (54%) and 28 of serogroup C (46%). Ninety-one point nine percent of
      the cases were found in patients under the age of 20. The annual rates of
      incidence ranged from 2.3 cases/100,000 inhabitants in 1990 to 3.4 cases/100,000
      inhabitants in 1996 with a slight decrease between these two dates. In patients
      under the age of 15 years, the rates of incidence ranged from 12.3/100,000 in
      1990 to 13.4 per 100,000 inhabitants in 1996. In the remaining years the rates
      decreased with a minimum of 2.2 cases/100,000 inhabitants. The incidence for N.
      meningitis serogroup C ranged from 0 to 0.9 cases/100,000 inhabitants between
      1990 and 1995. In 1996 the rate increased up to 2.6 cases/100,000 inhabitants.
      The rate of mortality was 6.6% and sequelae 8.7%. Since 1995 strains with
      decreased sensitivity to penicillin have been isolated, with percentages ranging
      from 20% to 56.25%. All strains remained sensitive to third generation
      cephalosporins and rifampicin. CONCLUSIONS: Neisseria meningitidis remains the
      most frequent etiologic agent of acute bacterial meningitis. The increase in
      serogroup C strains and the ever more frequent appearance of strains with
      decreased resistance to penicillin are confirmed, as is the persistence of high
      levels of endemia in our medium.

PMID- 9522515
TI  - [Usefulness of the disk diffusion method for evaluating the sensitivity of
      Neisseria meningitidis to penicillin and cefotaxime].
AB  - BACKGROUND: Routine susceptibility testing of Neisseria meningitidis to
      penicillin and other beta lactams is recommended after the isolation of N.
      meningitidis of moderately resistant to penicillin (MRP). We have evaluated the
      disk-diffusion method to determine susceptibility of N. meningitidis to
      penicillin (using disks of either penicillin or oxacillin) and to cefotaxime.
      METHODS: Fifty-four strains of N. meningitidis isolated from clinical samples
      were studied. MICs of penicillin and cefotaxime were determined by microdilution.
      Disks of 2 U of penicillin, 1 microgram of oxacillin and 30 micrograms of
      cefotaxime and two culture media, Mueller-Hinton agar (MHA) and MHA supplemented
      with 5% sheep blood (MHS) were used in the disk-diffusion assay. RESULTS: For
      disk of 2 U of penicillin assayed in MHA, 86.4% of the susceptible strains and
      20% of MRP strains were considered susceptible when a breakpoint of 28 mm was
      considered. None of the MRP strains was considered susceptible when using MHS,
      but only 38.6% of susceptible strains appeared as such on this medium. When a 1
      microgram oxacillin disk was used all MRP strains presented an inhibition zone <
      or = 10 mm on both MHA and MHS, but 54.4 and 4.5% of susceptible strains
      presented an inhibition zone > or = 11 mm on MHA and MHS, respectively. All
      strains were susceptible to cefotaxime, showing inhibition zones around a 30
      micrograms disk on MHA and MHS of > or = 35 mm and > or = 25 mm, respectively.
      CONCLUSION: Disk diffusion with cefotaxime (30 micrograms) allows to determine
      susceptibility of N. meningitidis to this antimicrobial agent. Discs of
      penicillin (2 U) and oxacillin (1 microgram) are not useful for screening of MRP
      N. meningitidis.

PMID- 9522516
TI  - [Epidemiology of Serratia marcescens between 1987 and 1995 at Vall d'Hebron
      Hospital].
AB  - BACKGROUND: Nosocomial infection have a relative high prevalence, which is
      necessary to reduce in order to improve the quality of patient care. The aims of
      this work is to study the behaviour of Serratia marcescens in our hospital as
      between 1987 and 1995. METHODS: Between February 1987 and March 1995 we detected
      679 isolates of Serratia marcescens in 504 patients. We used serotype as first
      marker and phagotype as second, and evaluation of PGFE as a discriminator of
      doubtful strains was done. RESULTS: 35.8% of the strains were from the
      respiratory tract, 37.2% from urinary tract; and 11.7% were isolated in blood
      culture, among them 23.3% came form children younger than 7 years. We noticed a
      tendency to decrease the number of isolates along the studied period. The most
      frequent serotypes were O:6, O:3 and O:2; representing the 36.0% of the total.
      Serotypes O:6;14, O:4, O:5, O:11 and polyagglutinables accounted for 37% of the
      total. The frequency was variable from year to year, and the predominant
      serotypes were different in every one of the hospitals in which the center is
      divided. A 60% of the patients were hospitalized in the General Hospital Vall
      d'Hebron building, in ICU (20%) and in chirurgical services (25%). Ninety-six
      patients had more than one isolate, 91 of them (94.8%) can be classified by
      phenotypic test. The PFGE is discriminatory in three of the five unclassificable
      isolates. In more than 35% of the patients the strains isolated along the time
      are different. The 66.7% of the patients acquired Serratia strains in the same
      admission, and in some cases with few days of difference. We detected 17 cross
      infections, predominantly in ICUs. With PFGE we could discriminate isolates which
      produced cross infections between patient who are not in the same hospital.
      CONCLUSIONS: Although the prevalence of Serratia marcescens is diminishing, it is
      able to produce crossed infections that, in general, affected few patients. The
      serotype and phagotype discriminate 94.8% of isolates. The PFGE is high
      discriminatory and reproducible, only 6.8% of the 44 strains tested by this
      method can not be typed.

PMID- 9522517
TI  - [Characterization of isolated adenovirus associated with acute lower respiratory
      infection in pediatrics].
AB  - BACKGROUND: Acute respiratory infection (ARI) are a health care problem as the
      adenovirus (ADV) has shown to be one of the most frequent viral agents detected
      in children admitted for mild ARI in the authors medium. METHODS: Over a 7-year
      period (1988-1994) ADV isolated from patients under the age of 5, admitted for
      mild ARI in hospitals in the city of Buenos Aires (Argentina). All the strains
      were isolated in HEp-2 cell cultures from nasopharyngeal aspirates in which the
      presence of ADV was detected by indirect immunofluorescence with monoclonal
      antibodies. Antigenic characterization was performed by sero- and genome
      neutralization with restriction enzymes. RESULTS: The isolates corresponded to
      the genomic variants of ADV 7i, ADV 7c and to a greater number of ADV 7h. An
      increase was observed in the quantity of cases in the second half of the year. In
      the population studied, the most commonly infected were males (67.9%) and
      patients from 2 months to 1 year in age (89.2%). Sixty-six percent of the cases
      were severe infections with the length of hospitalization being greater than that
      of patients normally admitted for mild ARI by other virus and showed a high
      mortality. CONCLUSIONS: All the above events suggest that the genomic variants
      detected are highly pathogenic.

PMID- 9522519
TI  - [Infection prophylaxis in neutropenic patients].

PMID- 9522518
TI  - [Pseudomonas aeruginosa bacteremia as a complication after endoscopic retrograde
      cholangiopancreatography].
AB  - BACKGROUND: The present was performed to describe the characteristics of
      bacteremias by Pseudomonas aeruginosa following cholangiopancreatography and the
      methods of prevention and treatment of the same. METHODS: Twelve different
      episodes of bacteremia by Pseudomonas aeruginosa were retrospectively studied in
      patients submitted to endoscopic cholangiopancreatography (ERCP) from 1993-1997.
      RESULTS: Three point six percent of the patients undergoing ERCP presented
      episodes of bacteremias by the microorganism in the 48 hours following the
      procedure. Except for one case, the patients presented obstructive disease in the
      form of calculi or neoplasms at the level of the biliary tree. In three cases,
      sphincterotomy had been carried out which was followed by clinical manifestations
      of hemorrhage in one case. Three patients (25%) died as a consequence of
      bacteremia and a hepatic abscess was developed in one case. The bacteremia
      appeared in successive outbreaks from 1993-1997. CONCLUSIONS: Bacteremia by
      Pseudomonas aeruginosa following ERCP is more frequent in patients with
      obstructive disease of the biliary tract and has an important additional
      morbimortality. It is associated with incorrect endoscopic disinfection. The use
      of drugs with an antipseudomonal spectrum should be considered as preendoscopic
      prophylaxis.

PMID- 9522520
TI  - [Subacute paresis of the lower limbs].

PMID- 9522521
TI  - [Conjunctival infestation by fly larva].

PMID- 9522522
TI  - [Pulmonary cystic image and anaphylaxis].

PMID- 9522523
TI  - [Cryptococcal arthritis as the initial form of human immunodeficiency syndrome].

PMID- 9522524
TI  - [Pulmonary and subcutaneous nocardiosis in an HIV-positive patient].

PMID- 9522525
TI  - [Clostridium perfringens sepsis in an immunocompetent patient. Presentation of a
      case and review of the literature].

PMID- 9522526
TI  - [Is resistant acid-alcohol staining losing specificity in the diagnosis of
      tuberculosis?].

PMID- 9522527
TI  - [Effect of preincubation of hemoculture vials in the detection of bacterial
      growth using the Bactec 9240 system].

PMID- 9522528
TI  - [Mycobacterium simiae disseminated infection in HIV patient].

PMID- 9522529
TI  - [Acute infantile myositis: a viral infection?].

PMID- 9522530
TI  - [Presence of urogenital mycoplasma in fertile women].

PMID- 9522531
TI  - [Working on a terminal: one more advantage of computerization in clinical
      microbiology].

PMID- 9522532
TI  - [Mupirocin].

PMID- 9522533
TI  - [Acupuncture--how effective is it really?].
AB  - Since acupuncture is now being used more and more in routine healthcare, the
      question as to its efficacy is certainly justified. The present article is an
      attempt to provide an answer by tabulating the results of controlled clinical
      trials relating to pain in general, osteoarthritis, back pain, asthma, giving up
      smoking, weight reduction, nausea and stroke rehabilitation. Although some
      studies have shown promising results, the efficacy of acupuncture has not been
      proven beyond reasonable doubt, except in the case of nausea, for which the
      evidence is unequivocally positive. It follows that the efficacy of acupuncture
      requires further clarification by suitable clinical trials.

PMID- 9522534
TI  - [The risks of complementary therapy methods].
AB  - Complementary treatments are currently more popular than ever-not least because
      they are perceived to be innocuous. This perception is, however, almost certainly
      wrong. Serious complications are being reported with worrying regularity, as is
      shown by the present article using acupuncture and herbal remedies as examples.
      The true incidence of such complications is, for the most part, unknown. Only
      when reliable figures have been provided by systematic investigation will it be
      possible to undertake a risk-benefit analysis. It follows that a study of this
      problem is now a matter of urgency.

PMID- 9522535
TI  - [Yohimbine in therapy of erectile dysfunction].
AB  - The bark of the yohimbine tree has long been appreciated as an aphrodisiac.
      Recent studies have shown that yohimbine is effective in the symptomatic
      treatment of erectile dysfunction. It is superior to placebo and has fewer side
      effects compared with the invasive treatment of erectile dysfunction. The
      evidence for effectiveness seems less compelling for other oral drugs used in
      this condition. It can be concluded that yohimbine is an attractive option in the
      symptomatic treatment of erectile dysfunction.

PMID- 9522536
TI  - [Case report from general practice. When "complementary" is forgotten.
      Hypokalemia as a differential diagnostic puzzle].

PMID- 9522537
TI  - [Cholestatic liver diseases--diagnosis and therapy. 3: Therapy of primary biliary
      cirrhosis].

PMID- 9522538
TI  - [What is "high normal" blood pressure?. Interview by Eckhard Bottcher-Buhler].

PMID- 9522539
TI  - [AIDS: when a nightmare becomes controllable...].

PMID- 9522540
TI  - [Safer sex--do new therapies promote risk taking?].

PMID- 9522541
TI  - [Atypical neuroleptics--the future of schizophrenia treatment?].
AB  - Since schizophrenia is not a rare occurrence and is often chronic, the general
      practitioner and internist providing primary care should also be informed on new
      developments in treatment with neuroleptics. A major new form of treatment is
      provided by the so-called atypical neuroleptics which, however, in terms of their
      receptor specificity are not a uniform group, and have only a few properties in
      common. A prototype of this group is clozapine (Leponex), which has a good
      antipsychotic effect and virtually no action on the extrapyramidal motor system
      (EPS). Whether clozapine is also capable of improving the primary negative
      symptoms of schizophrenia (e.g. flattering of affect, reduction of drive,
      cognitive disorders, etc.) has not yet been ascertained. On account of the rare
      but possibly fatal agranulocytosis it may induce, it may be prescribed only when
      certain safety precautions are taken. Risperidone (Risperdal) has similar
      efficacy against the classical positive symptoms, with no action on the EPS (up
      to a medium dosage), and has no hematological effects. Other atypical
      neuroleptics have recently become available: quetiapine, olanzapine and
      sertindole. They have at least some of the advantages of clozapine but a very low
      risk of producing hematological effects. However, before they are widely used in
      the doctor's practice, further clinical experience is needed.

PMID- 9522542
TI  - [Noncompliance--a typical problem in psychiatric patients. Individual, social and
      illness-specific factors].

PMID- 9522543
TI  - [Coping with psychoses in daily life. Social support exemplified by the Bavarian
      Society of Psychological Health. Interview by Dr. rer. nat. Anita Schweiger].

PMID- 9522544
TI  - [Vaccination noncompliance can actually have fatal sequelae. Severe vaccination
      deficits and inadequate prophylaxis: increase in infectious diseases].

PMID- 9522545
TI  - [Cholestatic liver diseases--diagnosis and therapy. 4: Diagnosis and therapy of
      primary sclerosing cholangitis].

PMID- 9522546
TI  - [1 in 100 children has too high blood pressure values. Interview by Dr. nat. rer.
      Anita Schweiger].

PMID- 9522548
TI  - [Leukotrienes promote inflammation and proliferation. Interaction with other
      mediator systems--modulation by therapeutic measures].

PMID- 9522547
TI  - [Ginkgo biloba special extract EGb 761--an anti-dementia drug].

PMID- 9522549
TI  - [Social inequality seriously compromises health].

PMID- 9522550
TI  - [Hospital utilization for acute problems of the elderly. Catalonia, 1982-1990].
AB  - OBJECTIVE: Analyse the total and causal hospital utilization in Catalonia from
      1982 to 1990 for the elderly. METHODS: Hospital admissions and the length of stay
      will be analysed using direct adjusted rates, age specific rates, percentage
      variation and the corresponding confidence intervals and significance tests.
      RESULTS: In population older than 65, male population have a greater hospital
      utilization and there is an increase in usage of hospitals with age. Sex
      differences are stressed among the elderly that in general population.
      Circulatory system diseases are the principal cause of admission in acute
      hospitals for the elderly of both sexes. CONCLUSIONS: Men and old people make
      greater hospital utilization. Circulatory system diseases comprise the major part
      of admissions in acute hospitals, even though other causes are gaining
      importance, especially mental disorders.

PMID- 9522551
TI  - [Smoking among nursing students in Catalonia: knowledge, attitudes and practice].
AB  - OBJECTIVE: Determine the prevalence and characteristics of tobaccoism, as well as
      some attitudes and their knowledge about tobaccoism in nursing university
      students in Catalonia. METHODS: A descriptive study with transversal section has
      been done. A self-filling anonymous questionnaire was designed following the
      guidelines of the European Regional Office of the W.H.O. We selected a sample of
      conglomerates of classrooms at random which was stratified according to levels in
      all the university schools in Catalonia. The field work was performed during the
      first term of the academic year 1994-1995 handing the questionnaires individually
      to the students and collecting them once filled. In the data analysis we used the
      ji squared test to Pearson with the Yates' correction and the lineal tendency
      test of Mantel-Haenszel. RESULTS: 904 students answered the questionnaire. The
      global prevalence of smokers is 38.7% (IC 95%: 35.8-41.6). There were no
      significant differences when considering levels or sex. The prevalence of
      tobaccoism in students over 24 years of age is 13% higher (p < 0.01) than in the
      group between 18 and 24 years of age. The group of daily smokers consumes an
      average of 12 cigarettes per day (DE: 5.9 cig/day). Significant differences were
      observed between smokers and nonsmokers in all the attitude variables analysed
      towards tobaccoism. 32% of third year students consider their knowledge is not
      enough in order to give advice against tobacco. CONCLUSIONS: A prevalence higher
      than 30% of the established objective in the Health Plan in Catalonia has been
      observed for the nursing professionals in the year 2000.

PMID- 9522552
TI  - [Validation of a questionnaire for retrospectively measuring occupational
      pesticide exposure].
AB  - OBJECTIVE: The aim of this study is to validate a questionnaire intended to
      assess retrospective occupational exposure to pesticides in a case control study
      of workers exposed to pesticides and congenital malformations. METHODS:
      Occupational data were gathered through personal interviews to 56 agricultural
      workers and this information was compared to: 1) personal interviews with the
      workers' foremen, 2) direct observation of working places and 3) another
      questionnaire self-administered previously by the workers as a part of the
      "Training Program for Pesticide Applicators". RESULTS: Accuracy and reliability
      indices are high for variables such as the crops where the interviewees have been
      working, the time period of the treatments with pesticides and the use of
      personal protection during treatments (sensitivity ranges between 0.81 and 1 and
      Kappa index ranges between 0.65 and 0.80). However, for variables such as the
      duration of the treatments and the pesticides used, sensitivity values range
      between 0.32 and 0.50. CONCLUSIONS: The results suggest that the questionnaire is
      a valid tool for measuring some items but in order to improve the quality of the
      exposure assessment the questionnaire was modified, including a question about
      size of treated areas (as a proxy variable for duration of treatments) and prompt
      lists were developed to make easier recall by the workers of specific pesticides
      used in treatments.

PMID- 9522554
TI  - [Relation of direct hospitalization costs with length of stay].
AB  - OBJECTIVE: Our main objective is to analyse to the relationship between the
      direct cost of a hospitalary discharge and the length of stay controlling for
      other care variables. METHODS: Analysis of the direct costs of pharmacy,
      laboratory, pathology and radiology tests of the 21,883 discharged patients in
      two Barcelona hospitals during 1993, in relationship to care variables contained
      in the basic minimum data set for discharged patient (BMDSDP). Using both
      hospital information systems in which are detailed the complete activity carried
      out and the assignment of unitary costs by means of different methods adapted to
      the available information, the direct cost is built up for patient and it is
      assembled by DRG. With the direct cost information and the care variables of the
      BMDSDP, a simple linear regression (least squared method) is carried out.
      RESULTS: The average direct cost is up to 31,533 pesetas. The regression by least
      squared method explains 70% of the variance (R2) and the variables with higher
      explanatory power are the length of stay and the relative weight of average DRG
      direct costs, that acts like variable of adjustment. CONCLUSIONS: The variability
      of the direct cost is explained principally by the length of stay. In addition,
      the length of stay is also very important on explaining the internal variability
      of DRG direct cost.

PMID- 9522553
TI  - [Obstacles to overcome in the control of pulmonary tuberculosis in the border
      region of Chiapas, Mexico].
AB  - OBJECTIVE: To improve the control of the pulmonary tuberculosis in the Border
      Region of Chiapas, Mexico. DESIGN: Academic researchers, health development
      workers from the nongovernmental sector and government health authorities met in
      a workshop to analyze recent experiences with tuberculosis. RESULTS: Among the
      important issues addressed were: with regard to official health services, the
      lack of resources, particularly medication, organizational problems which result
      in poor or absent communication within and among different health entities, the
      under diagnosis of cases and the lack of sufficient index of suspicion for
      tuberculosis among health personnel. With regard to the population at risk, there
      are profound socio-cultural barriers which include a lack of confidence in the
      quality of government health care centers and little attention given to chronic
      cough. Poorest, indigenous and more remote people have less access to care and
      are more likely to have advanced tuberculosis before seeking treatment if at all.
      New strategies proposed were to integrate communication efforts in tuberculosis
      control among all the involved health services, including private physicians,
      identify those patients at greatest risk, improve diagnostic skills of health
      providers, develop education campaigns in rural areas. CONCLUSIONS: Certain
      factors which impede better TB control seem amenable to change, others, such as
      severe poverty, particularly among peasants and indigeneous people, as well as
      the current political disruption, will require much broader intersectorial
      interventions.

PMID- 9522556
TI  - [Medical education].

PMID- 9522555
TI  - [Prevalence of tubercular infection among adolescents in Puerto de Sagunto].

PMID- 9522559
TI  - [Quality criteria and quality standards--social medicine expert assessment and
      its effectiveness in the social insurance system].
AB  - Basing on formulated criteria of expertises opinions in social medicine, the
      results of four investigations are presented aiming at the utilisation of expert
      opinions from external surveyors for social insurance. Leaving aside deficits
      that may be compensated, the results and assessments justify the view that
      consideration of only a few quality standards may increase the sociomedical
      competence and relevance of expert opinions.

PMID- 9522558
TI  - [Scope of social medicine 20 years after adoption into medical education-
      analysis test questions 1976-1996 by the IMPP (Institute for Medical and
      Pharmaceutical Test Questions)].
AB  - The list of educational objectives known as "Gegenstandskatalog" for each
      discipline within medical education should be represented in constancy at least
      in the sum of multiple-choice examinations which are part of German licensing
      regulations. All multiple-choice questions of social medicine which have been
      used within the last twenty years were looked up and compared with all the
      objectives of the discipline. The surprising results were: several objectives
      were highly overrepresented. Others never were asked for, among them such
      important ones as "social environment and illness", "cooperation in health
      systems" and "forms of organisation and impact of non-professional support
      systems". This result of the study undermines the commonly assumed close relation
      between official educational objectives and multiple-choice questions and
      therefore the composition of examinations in general. For other disciplines still
      no similar studies exist. Again it is necessary to ask what are really the
      educational goals and what are the educational objectives of all the disciplines,
      if not those of the "Gegenstandskatalog".

PMID- 9522557
TI  - [The present and future of social medicine].
AB  - There have been far-reaching structural changes in medicine in recent years,
      prompting us to review the social medicine from the time it was first officially
      included in the medical curriculum of instruction and examination of licensed
      physicians (1970) to the present day. This subdiscipline focuses on the specific
      interactions between medicine and society on the one hand and on the structures
      and functions of public health services in an ever-changing society on the other.
      Diseases and their sequels are considered to occur on a somatopsychosocial plane.
      Analysis of the close interaction between health and social factors affords a
      view on the problem of social inequality and disease or its sequels and the way
      they are attacked or overcome in our society, from the legal claim for assistance
      to the complementary help offered by a socially oriented structure of medicine.
      This is the range of operations of sociomedicine, concentrating mainly on
      prevention and rehabilitation. Epidemiological analysis is one aspect, individual
      social medical expertising another, both of them being important instruments in
      affording help within the framework of statutory health insurance allowances
      (sickness insurance, pension fund, medical care insurance, unemployment insurance
      and the like). In the future, increasing importance will be attached by
      reflecting the social consequences of developments in medicine and vice versa.
      This, in turn, will have an influence on the scientific and social approaches
      practised by social medicine.

PMID- 9522560
TI  - [GSG (Structured Health Regulation)-conforming documentation of surgical
      interventions in a university clinic--3 years clinical experiences 1994-1996].
AB  - The cost increase in the public health sector is steadily mounting and hence
      politicians are forced to redefine the economic conditions for regulations. As a
      new quality in the area of inpatient hospital care the new German law of
      structural health care (GSG), valid as of January 1, 1993 replaces the principle
      of covering full costs. The GSG law required in our hospital an adjustment of
      existing EDP structures with integrated automatic remuneration estimate and the
      installation of a medical structure of the organisation for complete and correct
      documentation. Weakpoints of the prescribed obligatory ICPM codes and inadequate
      legal regulations result in a lack of separation or wrong integration of the lump
      sum payment in individual cases (FP) and special compensation (SE). The summary
      analysis of the compensation system with a subsequent medical control system
      showed a primarily inaccurate classification by 12%. There is as yet no proof for
      the usefulness of a lump sum payment system resulting in a selection of risks.

PMID- 9522561
TI  - [Internal consistency and validity of work disability duration].
AB  - In this study results of a survey taken of persons insured under the public
      health care system were presented. The main objective of the survey was to
      determine the health of the insured on the basis of their subjective data, as
      well as to assess their prevention behaviour and their wish that the health
      insurance should offer prevention programmes. In addition, the health insurance
      provided data on how often the insured persons were unable to work for health
      reasons during a period of seven years. The data of work absenteeism are used to
      divide the group of respondents according to their health. To determine internal
      consistency it was first investigated whether persons with periods of disablement
      during one year (cross-section) also had long periods of disablement in the years
      before or after (longitudinal section). It was found that in the cross-section,
      persons with serious health problems (more than six weeks of disablement)
      differed little from those with average disablement periods (from one to six
      weeks) in the long-term development of disablement. The study also examined the
      correlation of periods of disablement and subjective data (validity). A mean
      correlation was found between the respondents' subjective assessment of their
      health and the length of disablement periods. There was also a significant
      negative correlation between internal health locus of control beliefs and the
      length of disablement. The results are discussed, and the ways and limits of
      using periods of disablement for empirical studies are presented.

PMID- 9522562
TI  - [Morbidity and health care costs of the elderly].
AB  - Pure demographic prognoses cannot adequately foresee the future trends in (multi
      )morbidity and costs of illness of the elderly. One has to take into account the
      current structure and distribution of morbidity in ambulatory and clinical care
      as well as the scientific hypotheses on different types of morbidity of the
      elderly which may be responsible for specific patterns of use of the health
      services and for the action taken by the health care system.

PMID- 9522563
TI  - [Morbidity spectrum and drug therapy of homeless persons in Munich].
AB  - In Germany there are currently approx. 200,000 homeless single people, and the
      trend is rising. As a result of the situation in which they find themselves, many
      of these persons are ill and in need of medical treatment. A study was performed
      in Munich/Germany, focussing on a medical practice providing care for the
      homeless, to investigate their illnesses and pharmacological therapy. The medical
      practice was located in a municipal shelter. Each year about 350 different
      destitute homeless men--about 15 per cent of all single homeless people in Munich
      -were cared for. The men, whose ages ranged from about 17 to 74 years were single
      and the majority lived in shelters, bed and breakfast accommodations, or shared
      apartments. About ten per cent lived on the street. For the study, 171 randomly
      selected medical records were analysed for the period of July 1994 to June 1995.
      The homeless men suffered principally from the following illnesses: psychiatric
      illnesses (36%), infectious and parasitic diseases (31%), skin diseases (30%),
      injuries (29%), diseases of the skeleton, of the muscles and of the connective
      tissues (28%), diseases of the respiratory organs (27%), cardiovascular diseases
      (24%), and diseases of the digestive organs (17%). Seventy-five per cent of the
      patients received drug treatment. In the case of 37% of the patients, wounds were
      treated and dressed in the medical practice itself. The most frequently
      prescribed drugs were: analgesics (12%), antibiotics (10%), antihypertensives
      (10%), gastrointestinal treatments (9%), treatments for colds (9%), and
      dermatopharmacological preparations (6%). It was surprising that only 16% of the
      psychic ill patients were treated with drugs, while over 60% of the other
      illnesses were mostly treated pharmacologically. The interaction with alcohol was
      the reason for that. The study showed that the practice did not sufficiently
      reach women and homeless people living on the street. The homeless situation, the
      personal and social difficulties faced by the homeless and the frequent misuse of
      alcohol caused many problems in medical treatment, such as low compliance.
      Special medical institutions like the Munich medical practice are capable of
      handling these problems. Co-operation with social relief organisations helps to
      improve the overall situation of the patient and also improves his state of
      health. These medical institutions are useful and necessary for providing good
      health care for the social fringe population, such as the homeless are.

PMID- 9522564
TI  - [Health insurance in Africa: a straw for the health care system].
AB  - Health Care Systems Clutch at a Straw: The health care systems of sub-Saharan
      Africa are facing a global crisis which is severely challenging their survival.
      Currently, alternatives to the traditional financing of health care by government
      grants and/or "fee for service" are sought. Otherwise the vast majority of poor
      rural inhabitants of these countries will lose access to Western medicine at the
      end of this century, making appropriate medical care a privilege of a small
      number of rich urbans. One approach to solving this crisis is the introduction of
      a health insurance system. However, the culture of African people must also be
      considered if one attempts to design and implement an insurance scheme. This
      paper reflects some of the problems of health insurance in an African context.
      Since the author contributed to the design of a "Community Based Health
      Insurance" of the Evangelical Lutheran Church in Tansania, this scheme is used
      here as an example.

PMID- 9522565
TI  - [Incidence of facial clefts in the Magdeburg region].
AB  - There is a varying frequency of oral clefts between different ethnic groups and
      several European regions: however, global investigations on the incidence of oral
      clefts over longer periods in Germany do not exist, because there has been no
      continuous system of registering malformations. Such a registration system has
      been in existence in Magdeburg, with a population of about 1.5 million and a
      yearly birth rate of about 8000 children, since 1980. A very high rate of oral
      clefts was found in Magdeburg, mainly a cleft lip with or without a cleft palate,
      which is a prevalence of 18.5 per 10,000 births. Twenty-two percent of all
      children with oral clefts had additional malformations. At a rate of about 10%,
      heart defects were most frequently combined with oral clefts. A significant
      prevalence increase was recorded in 1988 and 1989. Exogenous influences are being
      considered as a joint cause for this increase because of the prevalence peaks of
      neural tube defects from 1987 to 1989.

PMID- 9522566
TI  - [p53 as a biomarker in radiotherapy of carcinoma of the mouth cavity].
AB  - Multimodal therapy of oral squamous cell carcinomas today is based on surgery,
      radiotherapy and chemotherapy. Despite the combination of all three therapeutic
      options, there is still a large number of treatment failures and therefore major
      questions remain. Recent investigations suggest that mutations of the p53 tumor
      suppressor gene may account for some of the therapeutic failures. Inactivation of
      the gene may be an important determinant of the efficacy of today's multimodal
      therapy protocols. In 90 patients with squamous cell carcinomas of the oral
      cavity biopsy specimens were taken before and after preoperative
      radiochemotherapy. From all patients, biopsy and resection material was available
      for immunohistochemical analysis of p53. After radiation treatment, 51 patients
      (57%) showed a complete response; 39 patients (43%) only showed a partial
      response or did not respond at all. Among the responders, 82% of the
      pretherapeutic tumors were p53 positive, whereas among the nonresponders only 56%
      of the pretherapeutic tumors were p53 positive. The majority of the residual
      tumors were also p53 negative according to immunohistology after radiation
      treatment. In our study, detection of p53 protein by immunohistochemistry seemed
      to be connected with a more radiosensitive reaction of the tumors. Nevertheless,
      successful strategies for radiation therapy may need to take into account the
      tissue of origin and the status of p53 in the tumor.

PMID- 9522567
TI  - [Glossitis granulomatosa--an unusual subtype of Melkersson-Rosenthal syndrome].
AB  - So-called "glossitis granulomatosa", described in 1952 by H. Schuermann as a
      peculiar manifestation of Melkersson-Rosenthal syndrome (MRS), is little known in
      oral medicine due to the paucity of cases published so far. During the past 25
      years the author has observed eight definite cases of glossitis granulomatosa and
      confirmed its close connections with MRS. The recurrent inflammation tends to
      change into persisting macroglossia with considerable functional and sensory oral
      disturbances. The clinical diagnosis, histologically supported by biopsy, can
      definitely be established, yet the outcome of the mostly chronic macroglossitis
      (with danger of later tongue carcinoma) may be very doubtful. Knowledge of
      Schuermann's glossitis, a member of the group of etiologically unclarified
      lingual inflammations, is important for physicians involved in oral medicine
      because of its therapeutic and prognostic implications.

PMID- 9522568
TI  - [Endosseous implant management of tumor patients with the bone lock system. A 5
      year study].
AB  - The implantologic rehabilitation of patients after ablative oral tumour surgery
      and defect reconstruction is carried out generally without strict assessment of
      the successfulness of the outcome. Therefore 210 dental implants inserted in 58
      tumour patients were subjected to regular follow-up examinations for 5 years. The
      Bone-Lock osseointegrated implant system (Howmedica Leibinger, Freiburg) was used
      exclusively. The plaque index (Silness and Loe), the sulcus bleeding index (Loe),
      the pocket probing depth, the width of the passive peri-implant tissue, implant
      mobility by means of the Periotest method and bone resorption according to X-ray
      findings were ascertained. At 60-70% of measurement points a passive peri-implant
      tissue was created. After the beginning of loading, specific adaptation phenomena
      of tumour patients could be detected. Despite constant plaque accumulation (mean
      1.79), the bleeding disposition diminished from maximal 1.83 to 0.71.
      Corresponding to this finding the pocket probing depths decreased from 5.75 mm to
      4.57 mm. The implant mobility (Periotest method: mean 2.25, range -3 to +8.5)
      showed a decrease in the first 2 years, then the values increased. The mobility
      depends on the kind of supraconstruction. Ball attachments have the lowest and
      implant-supported bridges have the highest values. Peri-implant bone resorption
      showed 1.43 mm as a mean value of all measurements and had a horizontal component
      of 73-84%. In accordance with this the vertical bone loss was small. After an
      increase during the first 2 years both values reached a steady state around 2.5
      mm. The success rate for all 210 inserted implants is 83.2%. For implants in
      place for over 365 days the success rate is 93%. Prosthetic restoration in tumour
      patients can be achieved with osseointegrated dental implants according to the
      acknowledged international standards.

PMID- 9522569
TI  - [Glassman palatine expansion. Experiences with mono- and bimaxillary dysgnathia
      operations].
AB  - The median palatine suture has long been regarded as having the greatest
      resistance to dilatation of the maxilla. In 1984 Glassman [3] presented a
      conservative-surgical method of division of the palatineal suture in which only
      the lateral and anterior support of the maxilla is debilitated surgically. An
      orthodontic apparatus cemented in place preoperatively is already used
      intraoperatively for dilatation of the maxilla. In the period from 1991 to 1997,
      16 patients with a leptomaxilla and various dysnathic findings have been operated
      on at our clinic by the method described by Glassman. Sometimes the maxilla was
      dilated intraoperatively using the apparatus cemented in place by the method of
      Derichsweiler and dilatation was continued post-operatively until the described
      result was achieved. After successful dilatation of the maxilla and a stabilizing
      phase, a mono- or bimaxillary operation was performed. The use of this method led
      to the desired result in 15 patients. Dilatation of the maxilla was objectivized
      by determining the pre- and postoperative width of the anterior and posterior
      dental arch using models and X-ray of the occlusal overlay of the maxilla. In one
      patient who was operated on at the age of 38 years, a fracture of the alveolar
      process of the maxilla occurred unilaterally due to the completed ossification of
      the median palatine suture. The method of surgically aided dilatation of the
      maxilla at the level of Le Fort I plane is suitable for patients up to the age of
      30. In older patients, the median palatine suture should be transsected as well.

PMID- 9522570
TI  - [p53 mutations and HPV infections in squamous epithelial carcinomas of the head
      neck region. Long-term follow-up].
AB  - Mutations of the p53 gene are the most commonly observed genetic alterations in
      malignant tumors and are often associated with a loss of the tumor suppressor
      function of the p53 protein. We have analyzed specimens of head and neck squamous
      cell carcinomas (HNSCC) from 110 patients for p53 gene mutations and 92 of them
      additionally for human papillomavirus (HPV) infection in order to evaluate the
      prognostic significance of these factors by comparison with clinical follow-up
      data. Using the method of polymerase chain reaction (PCR)/temperature gradient
      gel electrophoresis (TGGE), mutations within the exons 5 to 8 of the p53 gene
      were found in 48 tumors (44%). Sequencing revealed missense mutations in most
      cases (15/20). Frequency of p53 gene mutations was not related to the tumor
      stage, the grade of differentiation, the presence of lymph node metastases, or
      the smoking history of the patients. With the help of a highly sensitive
      PCR/hybridization assay, an infection with the high-risk HPV types 16 and 18
      could be detected in 39/92 tumor specimens (42%). Follow-up data were obtained
      from 99 patients with a range of 2-112 months. No correlation of overall survival
      on the presence of p53 gene mutations or HPV infection could be observed. The
      absence of statistically significant correlations between p53 gene mutations and
      progressive disease, however, does not exclude its putative relevance in early
      phases of tumor development.

PMID- 9522571
TI  - [Syringomatous carcinoma of the facial skin. Case report of a rare tumor entity].
AB  - A rare case of well-differentiated syringomatous carcinoma of the nose, at first
      histologically misdiagnosed as morpheiform basal cell carcinoma, presented as an
      ulcerated nasal mass. Recurrence of the tumor and repeated histological
      examination of tissue specimens led to revision of the primary diagnosis. The
      histological features of the two entities are compared. The clinician should be
      aware that knowledge of the biological behavior of this tumor is sparse (based on
      less than 100 cases) and that the tumor possesses some features of malignancy,
      requiring a very careful and close follow-up.

PMID- 9522572
TI  - [Mandibular osteomyelitis after mandibular conduction anesthesia].
AB  - Several complications following a mandibular nerve block were reported in the
      literature. In some cases pterygomandibular abscess formation may be caused by
      mandibular needle injections. There is no report of odontogenic osteomyelitis of
      the ascending mandibular ramus in the literature. Here two patients with
      osteomyelitis of the ascending ramus following a mandibular nerve block injection
      are presented.

PMID- 9522573
TI  - [Leiomyosarcoma of the mandibular canal. Possible differential diagnosis of
      cystic processes of the mandible].
AB  - Leiomyosarcomas in the mandible are extremely rare. The cases of a 40-year-old
      woman with a leiomyosarcoma in the mandible is reported. Diagnostic and
      therapeutic problems are discussed.

PMID- 9522574
TI  - [Odontogenic fibromyxoma of the mandible].
AB  - Odontogenic fibromyxomas are extremely rare, benign odontogenic tumours, found
      preferentially in the second and third decades of life. They have a preference
      for the mandible. The present case report describes a 25-year-old patient with an
      odontogenic fibromyxoma in the lower jaw. Differential diagnosis, histology and
      therapy of this neoplasm are described.

PMID- 9522575
TI  - International meeting on intra-arterial chemotherapy in head and neck cancer.

PMID- 9522576
TI  - [Percutaneous transluminal angioplasty of the supraaortic trunks and extracranial
      internal carotid artery].

PMID- 9522577
TI  - [Urinary and sexual alterations in multiple sclerosis].
AB  - Urinary and sexual symptoms in patients with multiple sclerosis (MS) are
      frequent, although this question has scarcely been addressed in our country. The
      aim of this study is to prospectively evaluate the presence of such symptoms in
      77 MS patients. We have valued the neurological involvement and the degree of
      functional disability through the Minimum Dossier of Disability for Multiple
      Sclerosis. The urinary and sexual symptoms were collected through a directed
      survey. We have performed an urodynamic study in order to evaluate the bladder
      function. Urinary symptoms wire observed in 81.8% of patients, with predominance
      of the mixed syndrome (52%). Males show greater neurological affectation and
      functional disability, as well as greater urinary symptoms frequency (91%). The
      most frequent symptoms have been urgency (66.6%), frequency (60.3%) and dysuria
      (53.8%). The complications have been scarce, of infectious type (14.28%) and with
      female predominance. The most frequent urodynamic finding has been the detrusor
      hyperreflexia (60%). The minimum dossier of Disability for Multiple Sclerosis is
      useful to establish comparative parameters with other studies and with more
      specific urologic data. The presence of urinary symptoms in multiple sclerosis
      correlated with the degree of neurological (pyramidal and cerebellar) involvement
      and of functional disability in the Dysfunction Status Escale.

PMID- 9522578
TI  - [Vehicle drivers with Parkinson disease: behavior schedules of a patient sample
      from the Community of Madrid].
AB  - The aim of this study was to evaluate features of the disease, habits patterns at
      the wheel, and reasons to give up driving motor vehicles in subjects with
      Parkinson's disease (PD). Prospective study using a semistructured questionnaire
      comparing current or former drivers with PD patients and a control group matched
      for age, sex and social background. In a PD and movement disorders clinic in an
      university hospital. Sixty-two out of 166 PD subjects interviewed owned a driving
      licence. Only 19.2% of PD subjects were currently active drivers. Compared to
      parkinsonian ex-drivers, they were 6 years younger on average, most were in
      disease stage II, and were less often under antidepressant medication.
      Nevertheless, disabling motor fluctuations and dyskinesias were present in 19% of
      the patients. A 47% of the active drivers reported no difficulty at the wheel;
      the remaining declared to experience a wide range of difficulties, particularly
      to manage pedals or to assess distances properly. PD itself lead to driving
      withdrawal in 80% of ex-drivers in contrast to 6% of controls who stop driving
      due to other illness. Only 40% of PD subjects were driving 5 years after
      diagnosis. Medical advice was influential in deciding to stop driving in a single
      patient. Disease onset in early adulthood often allowed to keep driving for 10
      years or longer. Most subjects with PD give up driving during the first 5 years
      following disease onset, most due to the disease itself. Most active drivers
      adapt themselves to their physical circumstances, either by reducing the number
      of hours at the wheel or reducing speed. They are usually in early stages of the
      disease, despite which many experience subjective motor and visuospatial
      difficulties during driving. A minority keep on driving despite disabling
      fluctuations. This subset presumably represent a group at risk to suffer an
      increased rate of traffic accidents and in whom medical advice would be
      desirable.

PMID- 9522579
TI  - [Sixty-seven-year-old male with subacute progressive ataxia and extensive
      involvement of the lower cranial nerves].

PMID- 9522580
TI  - [Physiopathology of migraine].

PMID- 9522581
TI  - [Diagnostic criteria of Parkinson's disease and their influence on the prevalence
      of this disease in population studies].
AB  - Parkinson's disease is one of the most frequent chronic diseases. Prevalence
      varies widely across geographic areas and studies. Although geographic variation
      could be produced by environmental factors, most of the studies have different
      methodology, and the diagnostic criteria which have been used are not
      homogeneous. Population-based door-to-door studies are an accurate method for
      determining disease frequency in a community. This paper analyses diagnostic
      criteria in Parkinson's disease and its influence on the prevalence estimated by
      this type of studies.

PMID- 9522582
TI  - [Periodic movements of legs and sleep stages].

PMID- 9522583
TI  - [Patient with Hansen disease and lepromatous reaction with predominant neural
      involvement].
AB  - We describe a patient with a diagnosis of Hansen's disease borderline type,
      presenting as cutaneous lesions and silent multineuritis. Samples of nasal mucus,
      earlobe and cutaneous lesions were positive for acid-fast bacilli. He was given
      treatment with rifampin, dapsone and clofazimine. Five years later, he developed
      fever, poliarthritis, orchitis and hepatic involvement. Searching for acid-fast
      bacilli in many cutaneous and mucosal locations was fruitfulness. Because of
      clinical suspicion of erythema nodosum leprosum, he was treated with steroids
      with improvement of his clinical picture, but subsequently he developed
      multineuritis with many sensitive symptoms. A high number of bacilli was seen in
      nerve biopsy. We comment on atypical features of clinical evolution and erythema
      nodosum leprosum, and emphasize the significance of large number of bacilli into
      peripheral nerve in contrast with their absence at other levels.

PMID- 9522584
TI  - [Palpebral ptosis and blepharospasm secondary to hemispheric cerebral
      infarction].
AB  - A case that combines cerebral eyelid ptosis and blepharospasm secondary to
      cerebral hemisphere infarction is shown. EMG recording from the facial and eyelid
      muscles revealed lack of the levator palpebrae superioris, orbicularis oculi and
      corrugator muscles activity. Any voluntary opening attempt lead to a simultaneous
      contraction of the three muscles. Blink reflex responses were normal although
      showed facilitation features on the right side and mild inhibition
      characteristics from the left side. Median nerve SEP revealed a loss of
      precentral components (P22-N30) as well as a delay and amplitude decrease of N20.
      Transcranial magnetic stimulation disclosed a complete lesion of corticospinal
      pathway for right upper limb. In this case, a right hemisphere lesion caused an
      unusual eyelid motor abnormality: cerebral eyelid ptosis and blepharospasm
      induced by the voluntary eyelid opening.

PMID- 9522585
TI  - [Parry-Romberg syndrome: a form of focal vasculitis].
AB  - The Parry-Romberg syndrome (PRS), which was described many years ago, is a
      process of unknown etiology which evolves with invalidating lesions in one half
      of the face to which different neurologic, cutaneous or analytical abnormalities
      may be associated. A clinical, analytical and radiologic study of 5 patients in
      whom intracranial lesions were shown are herein presented. These findings,
      together with alterations in the cutaneous biopsies reported in the literature
      lead to the hypothesis that PRS may be due to a neurovascular alteration of
      immunologic basis, indicating antiinflammatory or immunosuppressive treatment.

PMID- 9522586
TI  - [Provision of a university teaching position and the post of the neurology
      department chief... and neurologists].

PMID- 9522587
TI  - [Meningitis due to Streptococcus bovis in a healthy woman].

PMID- 9522589
TI  - [Transitory hemi-chorea and lacunar infarction localized in contralateral
      putamen].

PMID- 9522588
TI  - [Wallenberg syndrome secondary to cardiac catheterization].

PMID- 9522591
TI  - [The 86th annual meeting of the Japanese Urological Association. Kagoshima,
      Japan. April 8-11, 1998. Abstracts].

PMID- 9522590
TI  - [The 68th annual meeting of the Japanese Society for Hygiene. Okayama, Japan.
      March 23-27, 1998. Abstracts].

PMID- 9522592
TI  - [Medical family therapy in children with chronic illness].
AB  - This article describes a medical family therapy approach to working with families
      of a child with a chronic medical illness. Medical family therapy combines the
      systemic paradigm of family therapy with the biopsychosocial paradigm of medicine
      to treat patients and families who are experiencing medical illness or
      disability. This article describes how family dynamics influence children's
      health and how children's health influences family dynamics. It then addresses
      special assessment issues, treatment issues, and collaboration issues for medical
      therapists when a child has a chronic illness.

PMID- 9522593
TI  - [Psychology and psychobiology of childhood trauma].
AB  - Exposure to overwhelming stress often determines how people subsequently organize
      their perceptions of themselves and of others. Traumatic experiences at different
      developmental levels have different effects on cognitive, affective and
      biological self-organization. Acute or chronic exposure to trauma may be
      expressed as Post Traumatic Stress Disorder (PTSD), dissociative disorders,
      somatic disturbances and alterations in perception of self and others. These
      disorders involve (a) the involuntary repetitive re-living of the trauma in
      thoughts, images, somatic states or behaviors, (b) attempts to avoid dealing with
      reminders of the past, (c) problems with the modulation of physiological
      responses to subsequent stress, and (d) a loss of capacity to engage in love and
      work with pleasure and satisfaction. The display of extremes of emotional
      distress, or of bizarre or disorganized behaviors, easily obscures the fact that
      current problems may have their origins in past trauma. The recognition that many
      psychiatric patients organize much of their lives around repetitive patterns of
      re-living and warding off traumatic memories, reminders and affective states, may
      help clinicians understand their symptoms as misguided attempts to regain a sense
      of control and safety, rather than as bizarre behaviors that need to be merely
      controlled. Since safe attachments appear to be the primary way in which children
      learn to regulate internal state changes, the negotiation of interpersonal safety
      needs to be the first focus of treatment. Since the labeling and categorization
      of emotional states is one of the principal areas of functioning that is
      disrupted by developmental trauma, treatment needs to include learning how to use
      words to understand and interpret feelings in general and stressful events, in
      particular. Since distrust and lack of social safety are critical parts of
      developmental trauma, structure and predictability are essential. Identifying
      specific trauma-based perceptions and expectations and learning how to negotiate
      the fulfillment of one's emotional needs are critical aspects of effective
      treatment.

PMID- 9522594
TI  - [Conditions facilitating social behavior disorder in children and adolescents in
      a clinic referred sample].
AB  - The patients referred to our center from 1989 to 6/1994 (n = 1076) were divided
      into three groups: "conduct disorder" (n = 235), "none psychiatric diagnosis" (n
      = 324) and "other psychiatric diagnosis" (n = 517). These groups were compared
      with regard to frequency, age, sex, the frequency of specific developmental
      disorders, the IQ, and the frequency of abnormal psychosocial circumstances.
      Additional the religiosity of the families and the televiewing of the children
      were investigated. Abnormal psychosocial circumstances and enlarged televiewing
      of the children were significantly associated with conduct disorders.

PMID- 9522595
TI  - [Blood doping].

PMID- 9522596
TI  - [Integrated treatment of alcoholism. Evaluation of its efficacy].
AB  - Patients with alcohol addiction are analyzed after one year from the beginning of
      therapy. Treatment is carried out by an Anti-addiction Service working in
      territory, an Hospital medical ward, anti-alcoholic clubs and Hospital voluntary
      groups. The method is described at first, then the answers of investigated
      patients, the abstinence period, the attendance to help groups, the use of drugs
      (disulfiram) and the emerged problems are considered and analyzed. More than one
      year later, patients with alcohol addiction who have followed this method are
      still in abstinence and have changed their habit from alcoholic to unalcoholic
      one, as just they have done for the behaviour and the relationship.

PMID- 9522597
TI  - [Respiratory medicine in the aged. Therapeutic problemsd].
AB  - Chronic obstructive pulmonary disease (COPD) is very common in the elderly, and
      its treatment needs special concern. Data from two clinical studies (in-patients
      of an Internal Medicine Department and Nursing-Home, respectively) have been
      evaluated in order to compare therapeutic approaches to COPD in three separate
      settings: home, hospital and Nursing-Home. Less than 50% of the overall patients
      received medical treatment according to the guidelines emerged in the literature.
      Although cardiovascular problems were highly common in out-patients, their
      bronchodilator therapy included systemic beta 2-agonists. Theophylline was the
      main drug prescribed to in-patients discharged from hospital, although inhaling
      beta 2-agonists were also recommended in few cases. Topical steroids have been
      widely used. Nursing-Home patients received mostly systemic steroids and few of
      them had theophylline and inhaling steroids. Anti-cholinergic drugs have never
      been employed in the overall population of elderly patients. Data concerning
      medical treatment of infectious respiratory diseases of Nursing-Home patients
      (both with and without COPD) have also been evaluated. Antimicrobial therapy has
      been performed according to the special needs of the elderly. During COPD
      reacutizations, beta 2-agonists and, again, theophylline consumption increased.

PMID- 9522598
TI  - [Usefulness of pulse oximetry in respiratory diseases].
AB  - The aim of the present study was to verify the usefulness and the limits of the
      pulse oximeter (po) in the management of patients with pulmonary disease. To this
      end oxyhemoglobin saturation measured with the po (SpO2) in 81 outpatients (mean
      age 67.7 +/- 12.7 years) was compared to oxyhemoglobin saturation calculated from
      a Radiometer computerized system (ScO2) and measured with a Co-oximeter (SaO2),
      considered as a reference value. Both SpO2 values and ScO2 values were, in
      average, significantly higher than SaO2 values (p < 0.001). In a multiple
      stepwise regression analysis, carboxyhemoglobin was the determinant of both SaO2
      SpO2 and SaO2-ScO2 differences. The relationship between SpO2 values and the
      arterial gas data revealed that a wide range of PaO2 and PaCO2 values could be
      related to a narrow range of SpO2 values showing a clear variability of PaO2 and
      PaCO2 for the same value of SpO2. These findings seem to indicate that the po can
      be regarded as a simple, non-invasive, and non-expensive method to measure the
      oxyhemoglobin saturation with a sufficient reliability. The SpO2 values could be
      used in the management and follow-up of patients with hypoxemia, but SpO2 values
      could be misleading in presence of hypercapnia and/or hemoglobinopathies.

PMID- 9522600
TI  - [Splenic vein thrombosis with pancytopenia and fever: antiphospholipid antibody
      syndrome].
AB  - Antiphospholipid antibody syndrome (APS) is now recognized as one of the most
      important causes of hypercoagulability. The most common site for venous
      thrombosis in APS is deep venous thrombosis of the lower extremities. Other sites
      of venous thrombosis include retinal veins, renal veins, and hepatic veins. The
      authors report a case of splenic vein thrombosis disclosing antiphospholipid
      syndrome in which also the cytolytic effect of aPL may play a role of "cofactor"
      in the genesis of thrombosis through the release of thromboplastin from the lysis
      of red cells, granulocytes and platelets, making them vulnerable to clearance by
      splenic macrophages. Important considerations are stressed about differential
      diagnosis, etiopathogenetic factors, therapy and follow-up of the patient.

PMID- 9522599
TI  - [Heart and autonomic nervous system in connective tissue disorders].
AB  - Heart rate variability (HRV) is a suitable diagnostic tool in identifying
      patients with autonomic nervous system (ANS) disorders even in pre-clinical
      stage. We have enrolled in this study all patients with large variety of
      connective tissue disorders, given the possibility of an involvement of ANS in
      these diseases. The study population consisted in eighty-five patients (68
      females and 17 males), 35 of whom affected by systemic lupus erythematosus, 16 by
      rheumatoid arthritis, 14 by Sjogren syndrome, 12 by progressive systemic
      sclerosis, 3 by Behcet syndrome and 5 by antiphospholipid antibodies syndrome.
      The mean age ranged between 33.7 of patients with lupus erythematosus and 51.8 of
      those with Sjogren syndrome. As control, we enrolled healthy subjects of
      different age, divided into two groups, to rule out the aging as potential source
      of considered parameters alteration. The autonomic function has been evaluated by
      24 hours ambulatory monitoring, using a Zymed 1210 Scanner with Zymed 3.74-PC
      1990 software. We have considered: in the time domain, the standard deviation of
      the RR intervals average (SDNN) and the percentage of RR adjacent intervals
      differing each other more than 50 msec (pNN50); in the frequency domain, the low
      (LF) and high (HF) frequencies, the LF/HF ratio, and the total power (RT). The
      HRV parameters resulted abnormal in every type of the connective tissue diseases
      considered: particularly SDNN, pNN50, LF, HF and RT (p < or = 0.01). IN
      CONCLUSION: the results of our study suggest that autonomic neuropathy may be
      present in any kind of connective tissue disorders even in preclinical stage.

PMID- 9522601
TI  - [Granulomatous hepatitis and fever of unknown origin].

PMID- 9522602
TI  - [Common variable immunodeficiency in an atopic patient with asthmatic
      manifestations].

PMID- 9522604
TI  - [Choices and costs of liver transplantation].

PMID- 9522603
TI  - [Superaspirin in the platelet aggregation inhibitor therapy].

PMID- 9522605
TI  - [Low molecular weight heparin].
AB  - Low-molecular-weight heparins (LMWHs) are obtained by depolymerization from
      standard heparin and show substantial advantages compared with the parent
      compound, by virtue of their different pharmacokinetics and lower interaction
      with platelets, so that they are supplanting heparin in various clinical
      indications. In the prophylaxis of venous thromboembolism, LMWHs are more
      efficacious than unfractionated heparin in patients at high thrombotic risk, and
      equally efficacious in patients at moderate thrombotic risk, with the benefit of
      once-a-day administration. In the treatment of acute deep venous thrombosis and
      pulmonary embolism, LMWHs administered subcutaneously in fixed dose per kg of
      body weight show equivalent efficacy and safety than intravenous heparin in
      adjusted dose, and allow home treatment in selected cases. In the treatment of
      deep venous thrombosis after the acute phase, LMWHs are equally effective and
      safer than oral anticoagulants. In unstable angina and non Q myocardial
      infarction, nadroparine and enoxaparin plus aspirin have been shown to be more
      efficacious than unfractionated heparin plus aspirin. In acute ischemic stroke,
      preliminary results are promising, but the evidence of efficacy must be
      substantiated by other studies, which are currently in progress.

PMID- 9522606
TI  - [Clinical evaluation in the early diagnosis of tuberculous meningoencephalitis].
AB  - In this short review, the Author evaluates the most important diagnostic problems
      about tuberculous meningoencephalitis. Any inadequate therapy can alternate the
      clinical picture and the results of the cerebrospinal fluid examination, and the
      clinical evaluation may become very difficult. The neuroradiological findings (CT
      and MRI), even when correlated to the typical neuropathological features of the
      disease, could be very sensitive but not specific. An accurate evaluation of the
      clinical context and, above all, of the clinical history, is the best way to
      avoid a tardive diagnosis and inappropriate therapies, and to choose which
      diagnostic procedures must be performed. In the latest years, the
      immunodeficiency status related to HIV infection, and the mobility of many
      persons from geographic areas endemic for TBC stressed the importance of this
      diagnosis. The extreme variability of the clinical picture is discussed, and the
      author describes the common manifestations as well as the rare syndromes
      associated with this disorder. The review indicates also the diseases with which
      the neurologist must challenge for a differential diagnosis. Some practical
      suggestions indicate how to minimize a diagnostic and therapeutic delay, for a
      disorder that in many cases is still lethal or leading to serious neurological
      complications or sequelae.

PMID- 9522607
TI  - [Valve diseases in the aged: when to operate?].
AB  - Valvular lesions, especially aortic stenosis, are not uncommon among the elderly,
      a sector of the population that is increasing in relative (extreme decrease in
      birth rates) and absolute terms (reduction of morbidity/mortality due to health
      and social advances), and their treatment presents a major challenge to the
      health system. Advanced age constitutes a surgical risk, but this is more likely
      due to a greater prevalence of comorbid conditions than to an intrinsic effect of
      old age. Moreover, the morbid effects of age are extremely variable, and an
      individualized evaluation of the problem is required. The decision to surgically
      intervene in an elderly patient must take into account of three aspects: a) that
      the valvular lesion has important hemodynamic consequences; b) that the symptoms
      are a product of the lesion and not of a concomitant disease, and c) that there
      is no comorbid condition whose symptoms and prognosis are even worse than the
      valvular disease itself. The psychological attitude of patients and their family
      members is also a factor to be considered. In severe aortic stenosis, valve
      substitution normally has a highly effective palliative effect, although at the
      cost of a moderately increased surgical risk. In mitral stenosis, preference
      should be given when possible to valvuloplasty with a balloon catheter. In
      degenerative mitral regurgitation, reconstructive techniques and prosthetic
      substitution with chordal preservation have considerably improved surgical
      outcomes, so that surgery is now indicated earlier to avoid the development of
      irrecoverable ventricular dysfunction. In mitral regurgitation of ischemic
      origin, structural damage (rupture of papillary muscle) must be differentiated
      from functional damage (dysfunction of papillary muscle); in the former, surgery
      is normally mandatory with a favorable outcome; in the latter the issue is more
      complex, and the possibility of improving the regurgitation by angioplasty of the
      culprit vessel must be thoroughly explored. The valvular sequelae of infectious
      endocarditis, a disease with higher incidence in old age, receive the same
      treatment at younger ages. Finally, in autochthonous tricuspid regurgitation,
      which can appear years after successful left side heart surgery, the decision to
      intervene is more difficult; in most cases it may be an expression of right
      ventricular dysfunction and a conservative approach would be indicated.

PMID- 9522608
TI  - [Cardiac tumors. I. General considerations. Benign primary tumors].
AB  - With the widespread use of echocardiography, cardiac tumors are no longer a rare
      disease. They are increasingly being diagnosed and surgically treated. In this
      review we present a practical classification of heart tumors, most common
      symptoms, diagnostic methods and guidelines for surgical treatment. Benign
      cardiac tumors are described specially in reference to pathology and surgical
      treatment. Cardiac myxomas are more extensively deal with.

PMID- 9522609
TI  - [Prognostic value of pre-discharge exertion echocardiography after acute
      myocardial infarct].
AB  - OBJECTIVE: The aim of the present work was to ascertain the usefulness of
      exercise echocardiography performed prior to discharge following acute non
      complicated myocardial infarction in the prognosis and detection of multi-vessel
      disease. PATIENTS AND METHODS: Sixty-five consecutive patients with primary
      episode of acute non-complicated myocardial infarction, with normal or slightly
      depressed ventricular function, were studied. Submaximal exercise test including
      echocardiogram pre- and immediately post-exercise were performed 7 to 10 days
      after infarction. Mean follow-up was 15 +/- 8 months; 15 patients presented
      angina, 9 revascularization and 1 died. RESULTS: Electrocardiographic ischaemia
      had low sensitivity and negative predictive value regarding complications (44%
      and 73% respectively); however, its specificity and positive predictive values
      were high (97% and 92%). In contrast, echocardiography-detected ischaemia showed
      much better sensitivity and negative predictive values (72% and 83%), with a
      slight decrease in specificity and positive predictive values (87% and 78%). Both
      remote ischaemia and the increase in global score > 0.25 during exercise were of
      high prognostic value (p < 0.001). Remote echocardiographic ischaemia yielded the
      diagnosis of multi-vessel disease with greater sensitivity than
      electrocardiographic ischaemia (84% vs 41%). CONCLUSIONS: Exercise
      echocardiography is highly useful in the prognostic assessment of patients prior
      to discharge following acute non-complicated myocardial infarction. The ischaemia
      detected on sub-maximal exercise and assessed by echocardiography was much more
      sensitive than that detected by electrocardiography in the prediction of new
      coronary events and multi-vessel disease.

PMID- 9522610
TI  - [Heart pathology of extracardiac origin. IV. Pulmonary hypertension in chronic
      respiratory diseases].
AB  - Pulmonary hypertension is the major cardiovascular complication of chronic
      respiratory disorders and its development is a sign of poor prognosis. Pulmonary
      circulation is characterized by its low vascular tone and the response to hypoxia
      by vasoconstriction. Pulmonary endothelium plays an important role in modulating
      these characteristics. Structural abnormalities of pulmonary arteries in
      pulmonary hypertension affect preferentially the intimal layer and may damage the
      endothelial cells. Endothelial dysfunction of pulmonary arteries has been
      recognized in the different forms of pulmonary hypertension. Vasodilators are
      recommended for the treatment of primary pulmonary hypertension. However, in
      pulmonary hypertension associated with chronic respiratory disorders, both
      systemic and selective pulmonary vasodilators are not indicated since they may
      worsen gas exchange due to the inhibition of hypoxic vasoconstriction. The most
      effective treatment of pulmonary hypertension associated with chronic hypoxic
      lung diseases is long-term oxygen therapy.

PMID- 9522611
TI  - [Intramural hematomas of the ascending aorta].
AB  - We present four patients with intramural hematomas in the ascending aorta.
      Diagnostic suspicion was aortic dissection in two of them. Prompt surgical
      procedures were performed in all of them. After reviewing other series, we
      conclude that ascending aorta hematomas should be treated as true aortic
      dissections.

PMID- 9522612
TI  - [Occult rupture of the aortic arch caused by a traffic accident].
AB  - A patient presented to our emergency department from another hospital diagnosed
      with pelvic fracture after a motor vehicle accident. In the ensuing 12 hours,
      chest pain developed, and a widened mediastinum on chest radiography was found.
      Posterior aortography showed aortic arch rupture. During surgery, we found a
      complete circumferential disruption of the arch between the brachiocephalic trunk
      and the carotid artery. Even though thoracic aortic injuries rarely occur in
      motor vehicle accidents, thoracic arch ruptures are extremely uncommon. This
      injury should be suspected after high-speed motor vehicle accidents, when
      accompanied with chest pain or widened mediastinum.

PMID- 9522613
TI  - [Emergency implantation of intracoronary stent after acute occlusion of the
      common trunk of the left coronary artery].
AB  - Nowadays, the implantation of coronary endoprosthesis within the left main
      coronary artery is not considered as an absolute contraindication. Here, we show
      a case of acute occlusion within the left main coronary artery. This was resolved
      by implanting a stent during a programmed cardiac catheterization. It should be
      stressed that this problem was occurred without manipulating the left coronary
      tree. In addition, the patient was in cardiac arrest when the stent was
      implanted. Cardiopulmonary resuscitation was applied because of this condition.

PMID- 9522614
TI  - [Fibrinolytic treatment of thrombus of the right atrium causing severe pulmonary
      embolism].
AB  - A case of acute pulmonary embolism and right atrial thrombus "in transit" treated
      with recombinant tissue plasmin activator is described. An early
      echocardiographic study in acute pulmonary embolism can detect right atrial
      thrombus in 15% of the time. It is well known that this finding is associated
      with poor prognosis, but the best treatment is controversial. The present case,
      in accordance with other previous reports, suggests the use of systemic
      fibrinolytic therapy in patients with right atrial thrombus and pulmonary
      embolism in course.

PMID- 9522616
TI  - [Changes in the treatment concepts in cardiovascular disease].

PMID- 9522615
TI  - [Pheochromocytoma and cardiac insufficiency].
AB  - Catecholamine-induced cardiomyopathy is a rare complication of pheochromocytoma.
      We present a case of pheochromocytoma that developed preoperative heart failure.
      Left ventricular dilation and severe hypokinesia were demonstrated by
      echocardiography. Heart failure was successfully treated with digitalis,
      diuretics and captopril. There were no surgical complications and the follow up
      showed and improvement on the systolic function evaluated by echocardiography and
      isotope ventriculography, 3 and 6 months after surgery. We review the
      pathophysiology and evolution of catecholamine induced cardiomyopathy. Preload
      reserve can be one of the adaptive mechanisms of the ventricle in catecholamine
      induced cardiomyopathy. Conventional therapy of hypertension and heart failure
      can be effective to correct the symptoms of cardiac dysfunction.

PMID- 9522617
TI  - [A review of infectious endocarditis due to Candida].
AB  - OBJECTIVE: As fungal endocarditis is a serious disease, frequently requiring
      cardiac surgery, a review was made of the experience of our Departments in this
      pathology. DESIGN: A retrospective analysis of clinical, echocardiographic and
      surgical data. SETTING: Patients studied in a tertiary care Hospital with cardiac
      surgery available. PATIENTS: Between 1984 and 1994 there were ten cases of
      candida endocarditis in nine patients, four male and five female, mean age--45 +/
      12 years (31-65). INTERVENTIONS: The following parameters were analysed:
      clinical (predisposing factors, clinical evolution, complications, therapy and
      mortality), echocardiographic (presence of vegetations, abscesses, valvular
      regurgitations). Patients studied in other Centres and referred to our Department
      only for examination (echocardiograms) were excluded from this analysis. RESULTS:
      Eight cases in seven patients were prosthetic valve endocarditis and two native
      valve endocarditis. No patient was drug addicted. Seven cases of prosthetic valve
      endocarditis developed less than one year after surgery and another had a
      gynecological fungal infection as the cause of the endocarditis. Four patients
      had had previous endocarditis. There were four embolic events and three developed
      heart failure. There were three perivalvular infections, six valvular
      regurgitations and only one case with huge vegetations on echocardiography. Nine
      patients were treated with amphotericin B, in five fluocytosin was added and in
      four ketoconazol, which was replaced by flukonazol in one patient. Therapy was
      continued for at least eight weeks. Six patients were operated during the acute
      stage and one died. One patient was operated on late after the infection. Three
      patients died during the active stage. In a follow up of 5.2 +/- 4.8 years (8
      months to 8 years) there was one fatal candida endocarditis relapse, one fatal
      candida sepsis, one non cardiac death, one patient developed a periprosthetic
      leak and one had recurrent systemic embolization. Abscesses/pseudoaneurysms were
      found in five out of seven patients submitted to surgery. CONCLUSION: Candida
      infective endocarditis has a bad prognosis, specially in those patients not
      operated early; it develops in patients with predisposing factors, which in our
      series were a previous infective endocarditis (four patients) and/or a prosthetic
      valve implantation less than one year before; it has important morbidity with
      multiple embolic events, perivalvular involvement, valvular regurgitation and
      heart failure.

PMID- 9522618
TI  - [Coronary disease in the postmenopausal woman. The experience of an intensive
      care unit over 10 years].
AB  - OBJECTIVES: Analysis of the characteristics of acute myocardial infarction in
      female patients admitted to a coronary care unit during a 10 year period. DESIGN:
      Retrospective analysis of computerized data collected during a 10-year period in
      every patient with acute myocardial infarction admitted between 1986 and 1995.
      SETTING: A coronary care unit of a central hospital. PATIENTS AND METHODS: Data
      on 2439 patients were analyzed in what concerns gender, age and hospital
      mortality. In the restricted group of 655 patients admitted between 1993 and 1995
      the prevalence of the following risk factors was assessed: arterial hypertension,
      dyslipidemia, smoking and diabetes mellitus. RESULTS: During a 10-year period,
      1918 male (M) and 521 female (F) patients were admitted, originating a 3.5 to 1
      M:F ratio. The M:F relation decreased from decade to decade from 11:1 in patients
      under 50 years old to 1.8:1 in patients over 70 years old. Hospital mortality was
      25.9% in female patients and 12.0% in male patients (p < 0.001). Mortality was
      similar in males and females until 60 years of age; significant differences were
      found only in the seventh decade of life (25% in females vs. 12% in males, p <
      0.001) and in patients over 70 years old (36% in females vs. 24% in males, p <
      0.005). Hypertension was significantly move prevalent in females (66% in females
      vs 46% in males, p < 0.001) as well as diabetes mellitus (31% in females vs. 20%
      in males). Similarly, a previous history of dyslipidemia was more frequently
      found in females than in males, but the difference was not significant (24% vs.
      19%, respectively). On the contrary, smoking was significantly less frequent in
      female patients (11% in female patients vs. 44% in male patients, p < 0.001).
      CONCLUSIONS: The probability of the occurrence of acute myocardial infarction is
      very low in premenopausal women. The M:F ratio decreases with aging. The risk of
      death progressively increases with age, and it is significantly higher in females
      in relation to males after the age of 60 years. Women, besides being older, have
      a higher prevalence of coronary artery disease risk factors, namely hypertension,
      diabetes mellitus and dyslipidemia.

PMID- 9522619
TI  - [Primary cardiac tumors: a review of 29 cases].
AB  - A series of 29 cardiac tumors were operated in Asturias Central Hospital between
      1974 and 1994. There were 23 benign and 6 malignant tumors. Among the benign
      neoplasms, 22 were myxomas and 1 lipoma; there were 6 remalignant tumors, one
      pulmonary artery sarcoma, two rhabdomyosarcoma, one mesothelioma and two
      lymphomas. We review the clinical findings of these patients. Long-term results
      were excellent in patients with benign lesions, and only one recurrence was
      found. In patients with malignant tumors, surgical procedures were only
      palliative and aimed at prolonging life; hence, prognosis remained unchanged.

PMID- 9522620
TI  - [Ischemic cardiopathy. Isomorphic forms of apolipoprotein A and their relation to
      coronary disease].

PMID- 9522621
TI  - [Depression of the ST segment in the V4-V6 leads in patients with an acute
      inferior infarct--an indicator of severe coronary disease].

PMID- 9522622
TI  - [Stress tests for the detection of coronary disease: a comparison between the
      sensitivity, specificity and predictive value of a computerized decision-support
      program and conventional assessment].

PMID- 9522623
TI  - [Post-myocardial infarct rupture of the interventricular septum. The prognostic
      factors of hospital mortality].

PMID- 9522624
TI  - [Kissing stenting--the initial experience and preliminary results].

PMID- 9522625
TI  - [Laser coronary angioplasty for an intrastent stenosis].

PMID- 9522626
TI  - [The role of abciximab in the prevention of the acute thrombotic complications of
      coronary angioplasty].

PMID- 9522627
TI  - [De-novo reversible stenoses in tortuous arteries during coronary angioplasty due
      to the accordion effect. A clinical case and review of the literature].
AB  - During the performance of PTCA, the operator must be able to differentiate true
      complications from pseudocomplications. Mechanical coronary shortening and vessel
      wall invagination due to accordion effect, "pseudo-transection", dissection,
      coronary spasm, and localized thrombosis are sources of iatrogenic obstruction
      during angioplasty. We report a case in which straightening of a right tortuous
      coronary artery during angioplasty produced an iatrogenic lesion that has a
      typical invaginate appearance. Conservative management is indicated in the
      absence of definitive angiographic aspect of vessel trauma, because they
      disappear after withdrawal of angioplasty equipment or adequate management of the
      guidewire.

PMID- 9522630
TI  - [What is your diagnosis? Juxtapapillary lipoma].

PMID- 9522631
TI  - [Cardiovascular risk patient--how much prevention is necessary and rational?].
AB  - Cardiovascular primary prevention may consist of strategies concerning the entire
      population (population strategy) or individuals at high risk for a cardiovascular
      event (high risk strategy). Clinicians are mainly involved in the identification
      and treatment of high risk individuals. Even more so, preventive measures should
      be focused on patients who are already affected by coronary artery disease (CAD)
      or other manifestations of atherosclerosis (secondary prevention). According to
      the beneficial effect anticipated by cardiovascular prevention, there should be a
      priority list guiding the therapeutic measures: first priority therapy should be
      reserved for patients with existing CAD, then persons without CAD symptoms at
      high risk for disease manifestation due to an accumulation of coronary risk
      factors (hypercholesterolemia, hypertension, smoking, diabetes mellitus, lack of
      physical activity, adipositas) should be treated. Third priority for preventive
      therapy for cardiovascular diseases is reserved for asymptomatic 1st degree
      relatives of CAD patients with an early onset CAD. Fourth priority have persons
      who are close relatives of high risk individuals, and fifth priority prevention
      is cardiovascular risk factor assessment in the general population. Estimation of
      the risk for future cardiovascular events is very important because it provides a
      rational basis for the necessity and relevance of a treatment strategy. In this
      review, several therapeutic options for cardiovascular prevention are described
      and discussed.

PMID- 9522632
TI  - [Control of blood pressure: a key factor in prevention].
AB  - An increase in blood pressure represents one of the most common conditions in
      daily medical practice. Many different factors are regarded as risk factors for a
      stroke. Hypertension, cardiac diseases, atrial fibrillation, smoking, diabetes
      mellitus, alcohol consumption and dyslipidemia are central stroke risk factors.
      The pathophysiological importance of these different risk factors is discussed.
      Hypertension represents the most prevalent risk factor for stroke in the general
      population. A decrease in blood pressure leads in general to a reduction of the
      risk. Besides an optimal pharmacological control of blood pressure miscellaneous
      non-pharmacological means should be implemented in any patient with high blood
      pressure. The most important non-pharmacological means of blood pressure control
      are discussed in the context of stroke risk.

PMID- 9522633
TI  - [Prevention of accidental falls in the elderly].
AB  - A variety of effective methods to prevent falls of the elderly are presented for
      everyday practice.

PMID- 9522634
TI  - [Secondary prevention of cancer].
AB  - Annual screening for cervical cancer is recommended from the onset of sexual
      maturity onward. Mammography has been recommended after the age of 50 to 70.
      Colorectal cancer should be looked for by hemoccult-test after 40 to 50 years of
      age. The negative consequences of false positive test results are in general
      considered acceptable. They seem unacceptable at the time being for cancer of the
      breast between 40 and 50 years of age and for cancer of the prostate.

PMID- 9522635
TI  - [Routine preventive vaccinations].
AB  - In 1996, a second measles, mumps and rubella (MMR) vaccination at the time of
      school entry was included in the Swiss Childhood Immunization schedule, and
      universal hepatitis B immunization will likely be added in 1998. An additional
      innovation is the possibility to use acellular pertussis vaccines which have a
      lower rate of side effects. Each physician who is involved in immunizations
      should be familiar with the arguments that support the official immunization
      recommendations in order to be able to provide competent advice to patients or
      their parents.

PMID- 9522636
TI  - [Public health and environmental protection. Political, legislative and public
      aspects].
AB  - Environmental and preventive medicine are closely related to each other as well
      as to politics and public awareness. To illustrate this, the example air
      pollution and the evolution of knowledge thereon are outlined and compared to
      four other environmental hazards: cigarette smoking, lead, asbestos and
      electromagnetic fields. The role of the media, of scientists, industry,
      legislation, and the courts in relation to each of the five hazards are assessed
      in a table.

PMID- 9522637
TI  - [Consensus conference on the therapeutic effects of L-carnitine in patients with
      myocardial ischemia and left ventricular remodeling].

PMID- 9522639
TI  - [Physiologic bases for the use of L-carnitine in cardiology].
AB  - L-Carnitine can affect cardiac function principally by improving fatty acid
      and/or glucose metabolism, by increasing perfusion due to modulation of the
      deformability of erythrocytes and/or vasodilatation, and by stabilising
      mitochondrial and plasma membranes of cardiomyocytes. While short-term
      administration of L-carnitine in vivo does not increase the muscular and probably
      also not the cardiac L-carnitine content, it improves the function of perfused
      rat or pig hearts in the reperfusion phase after ischemia. Long-term
      administration of L-carnitine increases the cardiac L-carnitine content in mice
      and has been shown to improve surrogate markers of coronary heart disease such as
      arrhythmias, nitrate consumption, and left ventricular dilatation and infarct
      size in patients after myocardial infarction. The only clear indication for L
      carnitine in cardiology is to date cardiomyopathy associated with primary L
      carnitine deficiency.

PMID- 9522640
TI  - [Therapeutic action of L-carnitine in myocardial ischemia and left ventricular
      remodeling: clinical data].

PMID- 9522638
TI  - [The effect of L-carnitine on ischemic heart disease: experimental results].
AB  - L-Carnitine is a key regulatory compound of glucose and fatty acid metabolism in
      the myocardium. A number of experimental observations indicate that L-Carnitine
      may favorably influence the outcome of the myocardium after ischemic injury.

PMID- 9522641
TI  - [The 95% confidence interval and the p-value].

PMID- 9522642
TI  - [Fatigue, general weakness, subcutaneous nodules].
AB  - A 58 year old female patient presented with subcutaneous nodules (adenocarcinoma
      on cytology) and general symptoms as first symptoms of advanced metastasizing
      cancer of the breast. The patient succumbed to metastatic disease and terminal
      bronchopneumonia a few months later. The path to diagnosis in a situation with
      diffusely metastasizing cancer, the differential diagnosis during evaluation and
      the rationale for the choice of investigations in a patient with far advanced
      metastasizing cancer but unknown primary site are discussed.

PMID- 9522643
TI  - [Elevated alkaline phosphatase].

PMID- 9522644
TI  - [Antisemitism in medical-natural science and philosophical writings of
      Paracelsus].
AB  - During the "Third Reich", the famous German medical doctor Paracelsus (1493/94
      1541) was often honoured as a forerunner of certain aspects of the "Nazi"
      ideology. Especially some invectives against jews in his medical writings were
      often quoted in this context. But was he really the "racial" antisemite as the
      Nazis wanted to see him? In the present study the authors demonstrate in detail
      that Paracelsus, like many christian scholars in the early modern period, indeed
      was a propagator of a clear-cut antisemitism. But although he often used
      antisemitic stereotypes, his antisemitism was in no way "racial", and he was not
      one of the extremely radical antisemites of his time.

PMID- 9522645
TI  - Hellenism postponed: some aspects of Renaissance medicine, 1490-1530.
AB  - This paper aims to draw attention to some of the problems in traditional accounts
      of the revival of classical medicine in the Renaissance. The rediscovery of Galen
      from 1525 onwards, and the success of Vesalian anatomy in the 1540s, have
      encouraged historians to read back into the period from 1490 to 1530 ideas
      promoted by only a handful of individuals, and to assume that the rhetoric of the
      reformers was swiftly successful. This was rarely the case. Few could read Greek,
      the manifesto of Leoniceno in 1490 demanding a return to Greek as the basis of
      medicine was hardly implemented before the 1530s. Instead, it was Latin authors,
      both from the past and among the new Humanists, who were most important in the
      transformation of medical ideas in the first quarter of the sixteenth century.

PMID- 9522647
TI  - [Otto Lubarsch (1860-1933) and pathology at the Berlin Charite from 1917 to 1928.
      From the trauma of war time destruction to the daily routine of a German national
      university teacher of the Weimar Republic].
AB  - This paper deals with the interdependence of medicine and society in a situation
      of political crisis. The example of the Pathological Institute at the University
      of Berlin illustrates how non-scientific, political measures exerted an influence
      on daily scientific work via the Science Ministry as well as the director and the
      staff of the Institute. Not only did financial problems of the German State and
      difficulties of the Prussian Science Ministry in keeping the Institute running
      hamper successful work in Pathology; moreover, the political ambitions of its
      director, Otto Lubarsch, and the changes in daily life as a result of the general
      situation of misery had their impact on scientific work. Therefore, an
      examination of the interdependence between medical science and politics should
      not be limited to physicians who are enrolled in a political party. Furthermore,
      research must be undertaken on the level of laboratory communities and everyday
      life with the help of archive material.

PMID- 9522646
TI  - [Early reception of Darwin's selection theory and its sequelae for comparative
      morphology today].
AB  - It is argued that Darwin's concept of evolutionary change is primarily based on
      the idea of functional adaptation. Genealogical aspects are seen as a secondary
      consequence of this hypothesis. Unfortunately, the reception of Darwin's work was
      concentrated on the genealogical aspects from the very beginning (Huxley,
      Haeckel) and thus channeled future development of evolutionary morphology in a
      very one-sided way. This direction of development led to the adoption of cladism
      as a very sophisticated concept of comparative morphology. Though cladism claims
      to contribute to our understanding of evolution, it is demonstrated that it
      suffers in this regard because of the incompatibility of "pure morphology" with
      the demands of functional thinking as an integrative part of Darwin's
      proposition.

PMID- 9522648
TI  - [Follow-up of the introduction of medical-natural science curricula into
      education].
AB  - A source-oriented research study that began with medieval library catalogs,
      provided the material needed to establish the organization und structuring of the
      teaching of natural science in monastic/convent schools. The further development
      of natural science from here to present-day teaching of biology was then traced.
      The wealth of material available since the late Middle Ages enabled the
      individual phases of development of this new teaching subject to be identified
      and their adoption into the Latin education system determined. This process
      revealed a series of different establishment phases. From the Middle Ages
      onwards, the study is based on teacher's and pupils' books known to have been
      used in the Latin education system, and, from the 18th Century onward, on an
      additional 7,000 or so school annual reports as well as, from the second part of
      the 19th Century, teaching curricula.

PMID- 9522649
TI  - [Mussels as therapy in ancient Crete].

PMID- 9522650
TI  - [TIPS--a therapeutic progress in portal hypertension].

PMID- 9522651
TI  - [Cerebrovascular circulation].

PMID- 9522652
TI  - [Antiviral prophylaxis and treatment of influenza].

PMID- 9522653
TI  - ["CADASIL"--a newly discovered hereditary cerebrovascular disease].
AB  - CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and
      Leucoencephalopathy) is a newly discovered inherited cerebrovascular disease
      characterized clinically by recurrent stroke-like incidents, dementia and often
      pseudobulbar palsy. Neuroimaging reveals intensive subcortical changes and
      pathologically one finds apparently systemic changes concerning the vessels such
      as thickening of the vessel wall, loss of smooth muscle cells and patches of
      granular material of unknown origin. The disease is not associated with
      atherosclerosis and vascular risk factors are missing or few. The CADASIL-locus
      maps to chromosome 19, but the gene has not yet been identified. Treatment and
      pathogenesis are unknown. In a Danish stroke population (The Copenhagen Stroke
      Study) no CADASIL-suspected cases were found among patients < or = 55 years,
      indicating a rare disease as far as Denmark is concerned.

PMID- 9522654
TI  - [Transjugular intrahepatic portosystemic shunt. Treatment of patients with
      recurrent bleeding from esophageal varices].
AB  - We report the results of transjugular intrahepatic portosystemic shunt (TIPS)
      procedure in six patients with liver cirrhosis and recurrent bleeding or acute
      intractable bleeding from oesophageal varices in spite of multiple sessions of
      sclerotherapy. Median follow-up was 15 months (range 1-24 months). The procedure
      was technically successful in all patients without procedure-related morbidity or
      mortality. Four of the procedures were performed electively and two as an
      emergency procedure. The portosystemic pressure gradient decreased to below 12
      mmHg following TIPS implantation and the shunt bloodflow was one quarter to three
      quarters of the portal bloodflow determined by Doppler ultrasound. Recurrent
      bleeding occurred in one patient but was amenable to endoscopic sclerotherapy. In
      this patient the shunt had developed a stenosis that was treated by
      balloondilatation and insertion of an additional stent six months following the
      initial procedure, and no further bleeding occurred. The remaining five patients
      had no rebleeding episodes. Repeated Doppler examinations in the followup period
      demonstrated patency of all shunts. None of the patients developed portosystemic
      encephalopathy. One patient died of cerebral haemorrhage, unrelated to TIPS, 16
      months following implantation. Another patient died 14 months following TIPS due
      to acute mesenteric occlusion and septicaemia. We conclude that TIPS is feasible
      and effective in selected patients with liver cirrhosis and persistent or
      recurrent variceal bleeding following repeated endoscopic therapy.

PMID- 9522655
TI  - [Transjugular intrahepatic portosystemic shunt in the treatment of portal
      hypertension].
AB  - The transjugular intrahepatic portosystemic shunt (TIPS) represents an important
      advance in the treatment of complications of portal hypertension. The results
      from the first 10 TIPS procedures in Arhus are reported. We found, as also
      documented in other clinical series, that TIPS is more effective in controlling
      acute haemorrhage than treatment with sclerotherapy and specific medical
      treatment. Seven out of 10 were treated for acute haemorrhage, and two patients
      were treated for recurrent variceal bleeding in spite of at least 20 procedures
      of sclerotherapy and pharmaceutical therapy. One patient was treated with TIPS
      due to refractory ascites. All 10 TIPS procedures were satisfactory, in four
      patients it was necessary to embolize collaterals. There were no acute
      complications associated to the TIPS procedures, but one patient developed
      stenosis of the shunt within one year, and another chronic encephalopathy. Two
      patients died, one because of sepsis with Candida albicans, and the other of
      intracerebral bleeding 16 months after the TIPS procedure.

PMID- 9522656
TI  - [The effect of parity on anorectal function].
AB  - An observational study of 144 (mean age 50 [range 45-57] years) perimenopausal
      women randomly selected from the National Register was conducted in order, to
      study long term effects of vaginal deliveries on anorectal function. The mean
      number of vaginal deliveries was two (range 0-6). Measurements were perineal
      position at rest and during straining, anal mucosa electrosensitivity, maximum
      resting pressure, maximum squeeze pressure of the anal sphincters, and pudendal
      nerve terminal motor latency. All tests were performed by a single investigator
      (AMR) who had no knowledge of the subject's parity. Increasing parity correlated
      with a lowered perineal position at rest (correlation coefficient (r) = 0.26, p =
      0.003) and during straining (r = 0.24, p = 0.006), an increased threshold of anal
      sensibility (r = 0.22, p = 0.008), and an increased pudendal nerve terminal motor
      latency (r = 0.27, p = 0.002). No effect of parity on 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 only accounted for a minor fraction
      of the total variability (between 3.6-5.7%). It is concluded that repeated
      vaginal deliveries have a long term adverse effect on anorectal function in a
      population of randomly selected healthy perimenopausal women.

PMID- 9522657
TI  - [Hepatitis C virus (HCV) status in recipients transfused with blood from anti-HCV
      positive donors].
AB  - Ten donors positive for antibodies to hepatitis C were discovered in the
      community of Aarhus after the introduction of screening of blood donors. These
      donors had donated blood products to 123 recipients. Of these recipients 76 were
      dead and 21 were not contacted for various reasons. Follow-up of anti-HCV status
      was performed in the remaining 26 recipients. Twenty-four (92%) of the recipients
      were positive in the RIBA confirmatory test, one was inconclusive and one was
      negative. Nine (90%) of the donors were hepatitis C virus RNA positive, while 17
      (68%) of the recipients were HCV-RNA positive. Altogether (donors and recipients)
      25 (76%) of the HCV-RNA positive patients had abnormal liver enzymes, while all
      HCV-RNA negative patients had normal enzyme levels. Eight of eleven HCV-RNA
      positive patients had an abnormal liver biopsy, while one patient in the HCV-RNA
      negative group had an abnormal liver biopsy. Three have been treated with
      interferon. In view of the liver damage already found only few years after
      transfusion, follow-up investigations in order to identify younger persons
      transfused with hepatitis C positive donations should be carried out and patients
      offered treatment if necessary. The National Board of Health has decided to
      recommend this strategy.

PMID- 9522658
TI  - [Randomized comparison of intravenous immunoglobulin and methylprednisolone pulse
      therapy in children with newly diagnosed idiopathic thrombocytic purpura. The
      Danish ITP Study Group].
AB  - Forty three children with newly diagnosed idiopathic thrombocytopenic purpura
      (ITP), platelet count (pl.c.) below 20 x 10(9)/l, and either clinically
      significant bleeding or failure to show a spontaneous platelet rise within three
      days of admission were randomly allocated to treatment with intravenous infusions
      of either immunoglobulin (IVIG) 1 g/kg or methylprednisolone (MPPT) 30 mg/kg on
      two consecutive days. Prompt induction of partial remission with pl.c. > 50 x
      10(9)/l after 72 hours was seen in 21/23 given IVIG versus 10/20 given MPPT
      (exact p = 0.003); mean pl.c.s after 72 hours were 188 versus 77 x 10(9)/l (2p <
      0.001). Poor responders were then given the alternative infusions in addition.
      After six days, complete remission with pl.c. > 150 x 10(9)/l was achieved in
      16/23 versus 10/20 (p = 0.16). During six months follow-up, there were no
      significant differences regarding relapse rates or chronic course. Eleven
      children with relapse were crossed over to the alternative treatment arm: the
      estimated treatment effect in pl.c. after 72 hours was 134 x 10(9)/l in favour of
      IVIG. These results indicate that IVIG infusions may be preferable to high-dose
      corticosteroids as initial treatment for children with ITP.

PMID- 9522659
TI  - [Delay from start of symptoms to hospital admission among 5.978 patients with
      acute myocardial infarction].
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. A group of 6676 consecutive patients with AMI, admitted
      alive to 27 Danish hospitals from 1990 to 1992, were studied. Due to missing
      information on delay or in hospital acute myocardial infarction 698 patients were
      excluded. Mean patient delay was 9.1 hours, median delay 3.25 hours (5 to 95
      percentiles: 0.67-40 hours). In multivariate logistic regression analysis patient
      delay was independently associated with male gender, increased age, diabetes
      mellitus, left ventricular systolic function (wall motion index), onset from
      midnight to 6 a.m., onset on a weekday, history of angina pectoris, chest pain as
      initial symptom, ventricular fibrillation or-tachycardia, Killip class > or = 3,
      presence of ST-elevation and ST-depressions. In conclusion, patient delay
      continues to be disappointingly long. This also applies to patients with a high
      risk of acute myocardial infarction (notably history of diabetes mellitus and
      angina pectoris).

PMID- 9522660
TI  - [Parvovirus B19--a cause of hepatitis in patients with liver transplantation,
      anemia in HIV positive individuals and encephalopathies in children].

PMID- 9522661
TI  - ["Back pain" and radiologists].

PMID- 9522662
TI  - [Treatment of dementia].

PMID- 9522663
TI  - [Medicine--what are we to believe?].

PMID- 9522664
TI  - [Fractures of the pediatric foot. "What heals during growth"?].

PMID- 9522665
TI  - [Fractures of the pediatric foot].
AB  - Some 13% of fractures in children are in the foot. Of these fractures, 50%
      involve the metatarsals and the phalanges. These are treated conservatively and
      do not cause therapeutic problems in general. In contrast, fractures and
      dislocations of the midfoot and hindfoot occur very rarely, so profound
      therapeutic expertise is lacking. The present paper takes stock and provides a
      critical assessment of the therapeutic concepts presented hitherto and new
      approaches to different problematic fractures. The long-term results of the
      literature and our own follow-up of dislocated intraarticular talus and calcaneus
      fractures which were not reduced anatomically has shown important problems in
      terms of pain, limited range of motion and malalignment in adolescence. In
      contrast to the findings in adults, no arthrosis was apparent in the radiological
      examinations. The findings were similar in mishealed Chopart dislocation and
      Lisfranc dislocation. The treatment of complex foot trauma is a multidisciplinary
      team approach. These challenging injuries should be treated only in centers where
      vascular and plastic surgeons are constantly available. The precise scientific
      assessment of foot fractures in children is confronted with the problem that so
      far too few cases have been evaluated. Rare problematic fractures (i.e. talus,
      calcaneus) require scientific work-up to establish a "gold standard" for
      operative and conservative treatment. This can only be accomplished in a
      multicenter study.

PMID- 9522666
TI  - [Treatment of humeral shaft fracture with intramedullary procedures (Seidel nail,
      Marchetti-Vicenzi nail, Prevot pins)].
AB  - Humeral shaft fractures can be treated either conservatively or operatively.
      Plating of the humerus is the established operative method, but recently interest
      has also been focussed on intramedullary nailing. Fifty-nine cases of humeral
      fractures treated with intramedullary nailing (Seidel/Marchetti-Vicenzi/Prevot)
      from January 1991 to December 1995 (44 fractures after trauma, 11 pathological
      fractures, 3 pseudarthroses, 1 re-fracture). Closed reduction in 55/59 cases. One
      infection (soft tissue); 2/48 pseudarthrosis (indication for nailing:
      pseudarthrosis!). No iatrogenic palsy of the radial nerve. Functional
      postoperative treatment in all 44 cases of humeral fractures after adequate
      trauma. One poor functional result: periarticular ossification after retrograde
      nailing, possibly connected with long-term respiratory treatment after trauma.
      Treatment of humeral shaft fractures by intramedullary nailing is favoured in our
      clinic (low complication rates, excellent or good functional results, limited
      approaches, small scars). Proximal fractures should be treated by the Seidel nail
      (stable interlocking of the proximal fragment); very distal fractures need Prevot
      nailing (reaming of condylar canals). All other fractures of the humeral shaft
      can be treated by each of the implants used in our clinic. Pathological fractures
      are an excellent indication for intramedullary stabilization. These patients
      benefit from stable fixation without intense surgical trauma. Pseudarthrosis,
      according to our limited experience, seems to require plating plus bone grafting.
      Plating is also recommended if revision of the radial nerve becomes necessary.

PMID- 9522667
TI  - [Comparison of internal fixation methods for the symphysis in multi-directional
      dynamic gait simulation].
AB  - For the stabilization of the ruptured pubic symphysis, rigid forms of fixation
      such as plate osteosynthesis and flexible fixations such as wire loops or PDS
      banding have been recommended. All methods have only been tested by static
      unidirectional loading until failure of the system. By this experimental
      arrangement Ecke and Hofmann found comparable results for flexible and rigid
      methods of internal stabilization of the pubic symphysis. They preferred flexible
      methods to maintain mobility of the symphysis and to prevent symphyseal fusion.
      We tested dynamic compression plate osteosynthesis, reconstruction plate
      osteosynthesis, wire loops and PDS banding for internal fixation of injured pubic
      symphysis in a dynamic multidirectional experimental arrangement simulating gait
      conditions. The specimens were loaded with 85 N in vertical (y-) direction and 34
      N in sagittal (z-) direction, which represent 50% of the forces acting at the
      pubic symphysis during walking and with a frequency of 1.5 Hz over 55,500 loads
      simulating the conditions over a 6-week mobilization period. Loading with 100% of
      the acting forces (corresponding to full weight bearing mobilization) led to
      early failure of the system. Our experimental analysis showed that neither wire
      loops nor PDS banding is able to stabilize the ruptured pubic symphysis, even
      immediately after fixation before loading. During the tests instability increased
      until failure of the system due to cutting of the bone or breaking of the wires
      or PDS banding. Success of plate osteosynthesis was dependent on the initial
      stability of the fixation. Overwinding of the screws, as in osteoporotic bone,
      lead to increasing loosening during repeated loading, whereas primary stable
      fixation of the screws was almost completely maintained during the test. In
      consequence, neither wire loops nor PDS banding should be used for stabilization
      of injured pubic symphysis if early mobilization with partial weight bearing is
      desired. Plate osteosynthesis (DC or reconstruction plate) tolerates early half
      weight bearing in patients with "open-book" injury only if safe screw fixation is
      guaranteed.

PMID- 9522668
TI  - [Proprioceptive abilities of surgically and conservatively treated knee joints
      with injuries of the cruciate ligament].
AB  - In the present study we evaluated proprioceptive capabilities of the knee joint
      with a balance test and correlated these findings to parameters which document
      mechanical stability. We compared 8 conservatively treated and 12 surgically
      treated patients with ACL-deficient knee joints with a control group of 12
      subjects. The balance test was performed with a Kistler force plate. Both the
      conservatively treated and the surgically treated patients showed significantly
      higher deviations of their centre of gravity than the control group. This was
      true not only for the injured leg but also for the noninjured contralateral leg.
      The differences were most remarkable when comparing the entire distance of centre
      of gravity deviations during 10 s. Additionally, the conservatively treated
      patients interrupted the test procedure significantly more frequently than the
      other two groups. We were not able to document any correlation between
      proprioceptive function and parameters for joint stability such as anterior
      drawer, Lachman, pivot shift and KT-1000 measurements. CLINICAL SIGNIFICANCE: In
      patients with conservatively or surgically treated ACL tears the rehabilitation
      of proprioceptive capabilities is mandatory both for the injured leg and for the
      noninjured contralateral leg in order to restore the function of the lower
      extremities. Reconstruction of passive stability alone is not sufficient.

PMID- 9522669
TI  - [Prospective comparison of MRI vs. direct magnification radiography in occult
      fractures of the scaphoid bone].
AB  - The diagnosis of occult fractures of the scaphoid bone is even more challenging
      than that of conventional fractures of the scaphoid. This study aimed to compare
      prospectively the gold standard method (plain radiographs in four projections,
      after about 14 days) and the primary findings with direct magnification
      radiography (DIMA) and magnetic resonance imaging (MRI). Primary MRI showed much
      higher diagnostic power than plain radiography at 10-14 days in occult scaphoid
      fractures and in detection of associated carpal injuries. This may lead to a
      decreasing time of disease. DIMA was inferior in detecting occult fractures of
      the scaphoid.

PMID- 9522670
TI  - [Contribution of soft tissue trauma and/or bone fracture to immune suppression
      after hemorrhagic shock in the animal experiment].
AB  - Bone fracture, soft-tissue trauma and hemorrhagic shock are frequent
      complications in trauma patients, and these patients are known to be
      immunocompromised. Nonetheless, it is difficult to differentiate the effect of
      soft-tissue trauma plus hemorrhage from that of bone fracture and hemorrhage on
      host immune function in the clinical setting. To determine this experimentally,
      closed bone fracture (right lower leg) and/or soft-tissue trauma (2.5 cm midline
      laparotomy) were induced prior to hemorrhagic shock (mean arterial BP of 35 +/- 5
      mm Hg for 90 min) in male C3H/HeN mice. All animals were killed at 72 h after
      initiation of the experiment and the spleens were collected aseptically. More
      significant depression of splenocyte IL-2 and IL-3 release occurred with the
      combined insult than after bony injury or tissue trauma alone with hemorrhage.
      The present study suggests that different traumatic insults, i.e. bone fracture
      as well as soft-tissue trauma in conjunction with hemorrhagic shock, produce
      comparable depression of host immune function. Moreover, combination of closed
      bone fracture and soft-tissue trauma prior to hemorrhagic shock leads to even
      more compromised immunity. This indicates that different mechanisms of immune
      depression may be involved following soft-tissue trauma or bony injury coupled
      with hemorrhage. The markedly depressed immune function following bony injury,
      soft-tissue trauma and hemorrhagic shock may contribute to the increased
      susceptibility of severely injured patients to sepsis and the ensuing multiple
      organ failure in the clinical situation.

PMID- 9522671
TI  - [Prospective randomized pilot study of ambulatory prevention of thromboembolism.
      2 times 500 mg aspirin (ASS) vs. clivarin 1750 (NMH)].
AB  - From March 1994 to March 1996, 287 patients, presenting with lower extremity
      injuries, who required immobilizing bandages or casts, where included in a
      prospective, randomized study. These patients received either low-molecular
      heparin or acetylsalicylic acid for thrombosis prophylaxis. In all patients a
      clinical examination and a colour-coded duplex sonography were performed after
      removal of the cast for detection of lower extremity venous thrombosis. A
      plebography was performed when thrombosis was suspected. A subcutaneous injection
      of divarin 1750 was given once daily in 143 patients. Thrombosis prophylaxis with
      Aspirin 2 x 500 mg administered orally was performed in 144 patients. Deep vein
      thrombosis occurred in 9 patients (6.3%) with clivarin prophylaxis and in 7
      patients (4.8%) treated with Aspirin. In both groups, no clinically significant
      side effects of the medications were observed.

PMID- 9522672
TI  - [Soft tissue tumors II. Treatment, multi-modality therapy concepts].

PMID- 9522673
TI  - [Late lesion of the brachial plexus after clavicular fracture].
AB  - Neurological complications in clavicle fractures are rare. As a primary lesion,
      it is caused by the trauma itself. More often however, the neurological symptoms
      develop later by large callus formation that encroach on the costoclavicular
      space. A case report is presented of delayed injury to the brachial plexus due to
      clavicular fracture with non-union and callus formation.

PMID- 9522674
TI  - [Rupture of the rotator cuff and skeletal muscle metastasis of primary lung
      carcinoma. A rare disease picture in differential diagnosis of shoulder pain].
AB  - Skeletal muscles is an uncommon site for metastatic spreading of malignancies
      such as carcinoma of the lung. Thus, to date, there have been only a small number
      of reports of carcinoma of the lung spreading to the skeletal muscles. This case
      study reports the rare combination of a rotator cuff lesion of the shoulder with
      the late occurrence of the metastasis of a squamous cell carcinoma of the lung in
      the ipsilateral deltoid muscle. The problems that result from this combination
      concerning diagnosis and therapy are discussed.

PMID- 9522675
TI  - [Specialist for trauma surgery].

PMID- 9522676
TI  - [Necrotizing soft tissue infections and "toxic shock syndrome"].

PMID- 9522677
TI  - [Limits of perceptual robustness in perspective distortion].
AB  - Pictures often do not appear distorted even when viewed at oblique angles. Three
      hypotheses have been put forth to explain this robustness of virtual space toward
      affine transformations. First, array specificity holds that the perception of
      depicted space is fully specified by the information available at the point of
      observation. Second, the notion of a compensatory mechanism involves an
      unconscious recreation of the scene according to the original viewpoint. Third,
      the indiscrimination hypothesis denies the ability of the visual system to
      resolve or detect affine transformations up to a certain degree. Three
      experiments were conducted to investigate these claims. Using a double projection
      technique devised by Cutting (1987), Experiment I showed that observers are able
      to discriminate and compensate, to some degree, for affine transformations if
      information about the projection surface is available. However, observers relied
      on relative image velocities rather than reconstructing the object. In Experiment
      2 additional observer motion was simulated. In single and double projection
      trials that required more difficult judgments of object rotation, compensation
      was poor and observers seemed to rely on local cues. Finally, real and simulated
      rotation of the projection surface revealed that observers are able to compensate
      for only one primary projection surface slant. The results reject the
      indiscrimination hypothesis and support the notion of array specificity.

PMID- 9522678
TI  - [Two-stimulus--two choice paradigm for psychophysics: range-frequency model and
      adaptation level theory in comparison].
AB  - The predictions provided by the range-frequency model and the adaptation-level
      theory were compared in respect of size judgments in an averbal two-category
      experiment. Squares of different sizes were presented in two different frequency
      distributions. After a two stimulus-two choice training, in which the subjects (N
      = 64) learned to which of the two response categories a relative small or large
      square belonged, a generalization context-series test followed. The two test
      series represented the two different frequency distributions used (the arithmetic
      mean was either smaller or larger than the median or midpoint). The percentage of
      large responses was registered. Furthermore, to investigate which experimental
      design would be appropriate for this research paradigm, the study was carried out
      using both a between-subjects and a within-subjects design. For the two
      experimental designs, the results pointed to a confirmation of the predictions
      provided by the adaptation-level theory (D. R. Thomas, 1993) but not the range
      frequency model (Parducci, 1983, 1995).

PMID- 9522679
TI  - [Semantic dimensions of vocabulary for emotional concepts].
AB  - The present paper analyzes the semantic features of positive and negative emotion
      names. In a pretest the 12 most typical positive rated emotion names were
      selected by means of a free listing of 70 Ss. These 12 items were presented to 42
      Ss as stimulus words for a free association test. From this association data
      overlap coefficients were computed and analyzed by means of nonmetric
      multidimensional scaling. It was possible to fit the features "Soziale Nahe
      Soziale Distanz" (social distance) und "Korperhaftigkeit" (Quality of body
      feeling) in the two-dimensional euclidian solution. In the same way as described
      above, an experiment was carried out with 11 negative emotion names. In this case
      it was possible to fit in the same two features and the feature "Aktivation"
      (activation).

PMID- 9522681
TI  - The prediction of criminal and violent recidivism among mentally disordered
      offenders: a meta-analysis.
AB  - A meta-analysis was conducted to examine whether the predictors of recidivism for
      mentally disordered offenders are different from the predictors for nondisordered
      offenders. Effect sizes were calculated for 35 predictors of general recidivism
      and 27 predictors of violent recidivism drawn from 64 unique samples. The results
      showed that the major predictors of recidivism were the same for mentally
      disordered offenders as for nondisordered offenders. Criminal history variables
      were the best predictors, and clinical variables showed the smallest effect
      sizes. The findings suggest that the risk assessment of mentally disordered
      offenders can be enhanced with more attention to the social psychological
      criminological literature and less reliance on models of psychopathology.

PMID- 9522682
TI  - Illusions of control, underestimations, and accuracy: a control heuristic
      explanation.
AB  - The illusions of control area is reviewed, and 5 conditions that influence
      control judgments are identified: skill-related factors, success or failure
      emphasis, need for the outcome, mood, and the intrusion of reality. It is
      proposed that individuals use a control heuristic that includes perceptions of
      intentionality and connection. Judgments of intentionality are based on
      foreseeability, ability to produce the effect, and valence of the outcome.
      Judgments of connection are based on the perceived association between the action
      and the outcome, which includes temporal, shared meaning, and predictive
      association. Effects of motives to overestimate, underestimate, and have accurate
      assessments of control are explained, using the concepts of hindsight bias,
      connection, and counterfactuals. In addition, the relation between the control
      heuristic and illusory correlation research and applications of the control
      heuristic to coping with chronic illness are explored.

PMID- 9522683
TI  - Situation models in language comprehension and memory.
AB  - This article reviews research on the use of situation models in language
      comprehension and memory retrieval over the past 15 years. Situation models are
      integrated mental representations of a described state of affairs. Significant
      progress has been made in the scientific understanding of how situation models
      are involved in language comprehension and memory retrieval. Much of this
      research focuses on establishing the existence of situation models, often by
      using tasks that assess one dimension of a situation model. However, the authors
      argue that the time has now come for researchers to begin to take the
      multidimensionality of situation models seriously. The authors offer a
      theoretical framework and some methodological observations that may help
      researchers to tackle this issue.

PMID- 9522684
TI  - Dissociations and dissociation theory in hypnosis: comment on Kirsch and Lynn
      (1998)
AB  - I. Kirsch and S. J. Lynn's (1998) critique of the neodissociation theory of
      divided consciousness fails to consider evidence of dissociations between
      explicit and implicit memory and perception in hypnosis. Contrary to their
      conclusions, evidence that the rate of hidden observer response (like other
      hypnotic responses) varies with the wording of instructions does not contradict
      neodissociation theory; rather, it underscores the fact that hypnosis entails
      social interaction as well as alterations in conscious awareness. Neodissociation
      and sociocognitive theories of hypnosis complement each other. Each draws
      attention to aspects of the experience of hypnosis that the other neglects.

PMID- 9522686
TI  - Dentin contamination protection after mechanical preparation for veneering.
AB  - PURPOSE: To evaluate in vivo the efficacy in preventing post-operative
      sensitivity and bacterial invasion of primed dentin that was left unprotected for
      4 days after laminate veneer preparation. MATERIALS AND METHODS: Twelve vital,
      periodontically involved anterior teeth were prepared for experimental laminate
      veneers and divided into three groups: (1) Control group, in which the prepared
      surfaces were left unprotected after preparation; (2) Prepared dentin surfaces
      were cleaned with Tubulicid Red Label and covered with Tubulitec Primer; (3) All
      Bond 2 Primer was applied to the prepared dentin surface. Post-operative
      sensitivity was evaluated immediately and a second appointment, 4 days later. The
      teeth were then extracted and examined by SEM. RESULTS: The application of a
      primer (Groups 2 and 3) prevented all sensitivity. After 4 days, the teeth in
      Group 1 were still sensitive to air blasts. Bacterial penetration into the
      unprotected tubules was observed in Group 1, but not in Groups 2 and 3.

PMID- 9522685
TI  - Diagnosis of approximal caries in primary teeth: radiographic versus clinical
      examination using tooth separation.
AB  - PURPOSE: To compare the accuracy of clinical examination performed with bitewing
      radiographs or clinical examination using tooth separation to identify carious
      lesion activity. MATERIALS AND METHODS: 320 surfaces from 40 bitewing radiographs
      were examined for approximal caries on the maxillary and mandibular primary
      molars of 20 patients 3-10 years old. The patients were divided into three
      groups: (1) Absence of the permanent first molar; (2) Partial eruption of the
      permanent first molar; and (3) Full eruption of the permanent first molar. Two
      examiners evaluated the radiographs using a megascope, a magnifying glass (x2),
      and an amplifying image screen. Approximal radiolucencies were identified on 72
      surfaces. Following the radiographic examinations, the two examiners performed
      conventional clinical inspection using a No. 4 dental mirror, a No. 5 dental
      explorer, and an air-water syringe, with artificial light and relative isolation.
      The separation method was performed with elastic bands, which were removed after
      24 hours, and the clinical examination conducted as in the non-separation group.
      RESULTS: The correlation between the extension of interproximal radiolucent
      lesions in primary dentition and their clinical diagnoses following separation of
      the teeth, was similar to findings on literature evaluating the permanent
      dentition. On radiographic findings for enamel lesions, white spots predominated
      both in the inner (100%) and in the outer (94%) half of enamel upon clinical
      examination with separation of teeth. For radiolucent lesions in dentin, on the
      other hand, cavities predominated over white spot lesions (84%). In Groups 1 and
      2 (young primary), white spots occurred in cases where the radiolucent lesions
      reached the dentin (15% and 25%), similar to findings for young permanent teeth.
      Clinical diagnosis performed with the mechanical separation of teeth cannot be
      considered conclusive for the primary dentition.

PMID- 9522687
TI  - Performance of composite finishing and polishing instruments after sterilization.
AB  - PURPOSE: To evaluate the performance before and after sterilization of Enhance
      and Min-Identoflex finishing and polishing systems on TPH and Z100 composites.
      MATERIALS AND METHODS: Finishing and polishing instruments consisted of a light
      cured resin cup impregnated with an abrasive and a silicon dioxide impregnated
      rubber cup. Sterilization methods included microwaving and autoclaving. RESULTS:
      Performance of the finishing and polishing instruments were affected more by the
      composite being finished and polished than by autoclaving or microwaving.

PMID- 9522688
TI  - Distortion of alloy by sandblasting.
AB  - PURPOSES: To measure distortion of alloy plates caused by sandblasting, and to
      determine the influence on degree of distortion of type of alloy, plate
      thickness, and sandblasting conditions i.e. particle size of alumina, air
      pressure, and duration of blasting period. MATERIALS AND METHODS: Plates were
      cast in a noble alloy and in a Co-Cr alloy. One end of the plates was fastened in
      a device, and the projecting 20 mm of the plates was sandblasted. Distortion was
      determined as the deflection of the plates at a distance of 20 mm from the
      mounting device. RESULTS: The mean deflections varied between 0.37 mm and 1.72
      mm. Plates of Co-Cr alloy showed less deflection than did plates of noble alloy.
      Deflection was increased by an increase in duration of the blasting, pressure,
      particle size of the alumina, and by a decrease in plate thickness.

PMID- 9522689
TI  - Chemical treatment of cavity walls following manual excavation of carious dentin.
AB  - PURPOSE: To improve the conditioning of cavity walls resulting from minimal
      mechanical preparation of carious lesions, such as is done in modified Class II
      tunnel preparations. MATERIALS AND METHODS: Proximal carious lesions in premolars
      and molars were excavated manually and the cavity walls studied using a
      stereomicroscope and by scanning electron microscopy (SEM) following treatment
      with either polyacrylic acid, sodium hypochlorite, the enzyme preparation
      Pronase, or sequential combinations of the agents. Polyacrylic acid (10%) was
      used according to the manufacturer's instructions, while concentrated sodium
      hypochlorite (5.25%) was applied with either intermittent scrubbing or with
      ultrasonic energy for 5-10 minutes, or the cavity wall was incubated with the
      agent at +/- 37 degrees C for periods up to 24 hours. Incubation with the
      proteolytic enzyme preparation Pronase was carried out at 37 degrees C for a
      period up to 48 hours. RESULTS: Manual excavation did not remove all carious
      dentin, neither did treatment with polyacrylic acid. Scrubbing or sonication with
      ample amounts of sodium hypochlorite, followed by treatment with polyacrylic
      acid, or prolonged incubation with sodium hypochlorite, removed most of the
      remaining carious dentin. However, the "cleanest" surfaces were obtained after 48
      hours of incubation with Pronase. Spots of thicker, soft layers of decayed dentin
      that were left intentionally at some locations could be disintegrated only by the
      Pronase treatment. It was concluded that treatment with sodium hypochlorite and
      polyacrylic acid in tandem, or with Pronase may represent potential supplements
      to conventional cavity cleaning that deserve further investigation. In the clinic
      more efficient cavity cleaning may improve the bonding ability and thus reduce
      the risk of marginal ridge fracture in teeth with Class II tunnel restorations.

PMID- 9522690
TI  - Marginal integrity of bonded amalgam restorations.
AB  - PURPOSE: To evaluate the marginal integrity of amalgam restorations in
      association with four different bonding agents in an in vitro stressing system.
      MATERIALS AND METHODS: Cylindrical cavities were prepared in extracted human
      molars. The enamel-dentin interface of each cavity was treated with one of four
      different bonding agents and a non-bonded group. Following treatment with one of
      the four systems; Amalgambond (AB), Amalgambond Plus (AP) Superbond D-liner II
      (SD) and Bond-It (BI). Each cavity was then restored with a high-copper spherical
      amalgam alloy Tytin (TY). Using a load of 75 Newtons (N), a total of 100,000
      cycles were applied to each restoration surface. Marginal integrity of each tooth
      restoration interface was replicated with epoxy and evaluated for gap width with
      a profilometer and SEM. RESULTS: There were no significant differences in gap
      width between the loaded and unloaded groups. The non-bonded group (before
      loading) was statistically different than AB, AP, and SD. In addition, there were
      no significant differences among the 4-META bonded groups, regardless of the type
      of bond system, whether loaded or unloaded. The four different bonding agents
      were significantly different after loading than the non-bonded group. Our SEM and
      profilometry data demonstrate that the marginal integrity of amalgam alloy
      restorations is significantly improved by use of bonding systems.

PMID- 9522691
TI  - 2-year clinical evaluation of dentin bonding systems.
AB  - PURPOSE: To clinically evaluate dentin bonding systems. MATERIALS AND METHODS:
      Eighty Class V carious lesions were prepared and restored with four different
      adhesive systems: Clearfil Liner Bond/Clearfil Photo Anterior, Scotchbond Multi
      Purpose/Silux Plus, Syntac/Heliomolar, and Gluma 2000/Pekalux. All restorations
      were evaluated at baseline, after 1 year and 2 years using the USPHS criteria.
      RESULTS: No significant difference was noticed between the tested materials after
      1 year. However, the 2-year results revealed that the restorations of Groups 1
      and 2 were superior to restorations of Groups 3 and 4. Adhesive systems that
      remove the smear layer and have a substantial lining function performed better
      than those that only modify the smear layer.

PMID- 9522692
TI  - Dentin bond strength of fluoride-releasing materials.
AB  - PURPOSE: To evaluate the shear bond strength to dentin of fluoride-releasing
      materials. MATERIALS AND METHODS: Human, noncarious extracted permanent molars
      stored in distilled water were used. Flat buccal and lingual dentin surfaces were
      ground wet on 600-grit silicon carbide paper. The teeth were then distributed at
      random into three groups of 8 teeth (16 surfaces) each: Group 1: Compoglass;
      Group 2: Fuji II LC; Group 3: Dyract. Cylindrical samples of the materials were
      prepared in plastic molds and bonded to the dentin surface according to the
      manufacturers' instructions. All samples were placed in distilled water for 24
      hours, thermocycled for 500 cycles in distilled water at 6 degrees C and 60
      degrees C and sheared with an Instron at a crosshead speed of 0.5 mm/minute.
      RESULTS: In MPa: Group 1: 16.29 +/- 5.35; Group 2: 15.42 +/- 4.77; Group 3: 15.33
      +/- 6.96. ANOVA revealed that there was no statistically significant difference
      between the groups. Fracture patterns, examined with the SEM, revealed material
      cohesive failures for all groups.

PMID- 9522694
TI  - Significance of pulpal pressure during clinical bonding procedures.
AB  - PURPOSE: To determine whether pulpal pressure in vital teeth plays a significant
      role in dentin bonding procedures. MATERIALS AND METHODS: Half the teeth in three
      baboons received root canal treatment thus eliminating pulpal pressure. All teeth
      were then prepared on the buccal surface with a diamond wheel to create flat
      surfaces into dentin, measuring at least 4 mm in diameter. Dentin bonding systems
      from two manufacturers were applied. Using a Bencor tensile nozzle freehand, 3.5
      mm diameter composite buttons were bonded to the prepared surfaces. The animals
      were sacrificed 24 hours later, the teeth removed and mounted in specimen rings,
      using the same Bencor tensile nozzle for proper axial alignment. The composite
      buttons were tested for shear bond strength in a tensometer. RESULTS: The results
      showed no statistically significant difference between the two materials tested,
      furthermore there was no difference in SBS between materials bonded to vital or
      non-vital teeth. After completion of the tests, 20 teeth (10 for each dentin
      bonding system) were prepared according to standard laboratory procedures for a
      dentin bond strength test using the Bencor Multi-T system. The values obtained
      were higher, but again there was no statistically significant difference between
      the two systems.

PMID- 9522693
TI  - Clinical evaluation of Dyract in primary molars: 1-year results.
AB  - PURPOSE: To evaluate the 1-year clinical performance of Dyract in primary molars.
      MATERIALS AND METHODS: 55 children (aged 4-9 years) received 1-3 restorations (n
      = 91) utilizing Dyract, a new restorative material combining properties of both
      glass ionomers and composites. RESULTS: The so-called compomer material showed
      good handling characteristics and a survival rate of 97% after 1 year.
      Nevertheless, the material demonstrated an average wear of 190 microns during 1
      year, with 67% of the restorations having occlusal wear of less than 200 microns.
      The combination of a low failure rate and the ease of application makes the
      compomer material very suitable for application in the primary dentition.

PMID- 9522695
TI  - Evaluation of adhesive systems using acidic primers.
AB  - PURPOSE: To evaluate in vitro the dentin and enamel shear bond strength of two
      adhesive systems that contain acidic primers. MATERIALS AND METHODS: Clearfil
      Liner Bond 2 (CLB2) and Denthesive II (DTII), containing acid primers were used
      with (ETCH) and without (NOET) etching. Scotchbond Multi-Purpose (SBMP) was
      utilized as a control. Sixty flat enamel and dentin bonding sites were prepared
      to 600 grit on extracted human molars. Both acidic primer systems were used with
      (ETCH) and without etching (NOET) for both enamel and dentin surfaces. The
      control group used etching only. After applying primer and adhesive, a microfill
      composite (Silux Plus) was placed in a 2.5 mm diameter matrix on the tooth
      surface, and polymerized for 40 seconds. All specimens were thermocycled 500
      times. Shear bond strengths were determined using a Zwick testing machine.
      RESULTS: One-way ANOVA revealed significant differences among groups for enamel
      (P = 0.0001) and dentin (P = 0.0002). Duncan's multiple range test (alpha = 0.05)
      revealed that enamel shear bond strength of DTII-ETCH was equal to that of CLB2
      NOET and these were significantly greater than CLB2-ETCH, SBMP and DTII-NOET. For
      dentin, bond strengths for CLB2-ETCH and CLB2-NOET were significantly greater
      than DTII-NOET.

PMID- 9522696
TI  - Bonding mechanism of three "one-bottle" systems to conditioned and unconditioned
      enamel and dentin.
AB  - PURPOSE: This in vivo study investigated the formation of hybrid layer, resin
      tags and adhesive lateral branches, by use of the latest generation of enamel
      dentin bonding systems ("one-bottle" systems) on conditioned and unconditioned
      enamel and dentin. MATERIALS AND METHODS: The dentin adhesives were tested on 24
      flat dentin preparations made on facial surfaces of vital, periodontally
      compromised teeth. The experimental teeth were randomly divided in six groups of
      four samples each. Group 1: Prime & Bond 2.1 (conditioned dentin, CD); Group 2:
      Single Bond (CD); Group 3: Syntac Sprint (CD); Group 4: Prime & Bond 2.1
      (unconditioned dentin, UD); Group 5: Single Bond (UD); Group 6: Syntac Sprint
      (UD). In the first three groups, the "one-bottle" systems were applied following
      the manufacturers' instructions, while in the other three groups the dentin and
      the enamel were not treated with phosphoric acid and the primer was applied
      directly on the prepared surfaces. On top of the primer-adhesive, a thin layer of
      resin was applied and light-cured for 20 seconds. The sample teeth were extracted
      immediately after the adhesive material was light-cured. All the samples were
      split-fractured along their long axis. Half of the samples were deproteinized and
      decalcified at the interface in order to visualize the hybrid layer and the other
      halves were completely dissolved in order to observe the morphology of resin tags
      by use of scanning electron microscopy. RESULTS: Groups 1-3: All the tested
      products showed the same micromechanical bonding mechanism to conditioned dentin
      with phosphoric acid: they formed hybrid layer, resin tags and adhesive lateral
      branches. In the samples of the first three groups, characteristic reverse cone
      shaped tags with their corresponding adhesive lateral branches were evident. At
      the enamel site, traditional pattern of etch enamel was always observed. Groups 4
      6: When the bonding systems were applied on unconditioned dentin, hybrid layer
      was not formed, resin tags were rarely noted and their shape was narrow and they
      did not completely seal the tubular orifices. The tubules remained mainly closed
      by smear plugs. At the enamel site, the unetched surface showed absence of
      characteristic etch pattern and of resin tags.

PMID- 9522697
TI  - Marginal morphology of Class V composite restorations.
AB  - PURPOSE: To evaluate the morphology of enamel and dentin margins of Class V
      restorations filled with different resin composites and glass ionomer cements by
      SEM examination of replicas. Microleakage was also evaluated between the
      restorative materials and dentin and enamel at different levels. MATERIALS AND
      METHODS: Non-retentive Class V cavities were prepared in extracted third molars
      on buccal and lingual surfaces at the CEJ level. Each material was used according
      to manufacturer's directions. Immediately after finishing, an impression of each
      restoration was made using a polyvinylsiloxane material to obtain an epoxy resin
      replica. Each replica was inspected under SEM to evaluate the morphology of the
      margin along the cervical-dentin and incisal-enamel junctions. Each tooth was
      then stored in dye solution (erythrosin B) for 24 hours. First an evaluation was
      made along the restoration margins to evaluate circumferential leakage. After
      longitudinal sectioning, leakage was calculated along the cavity wall in dentin
      and at the enamel interface (longitudinal leakage). RESULTS: Enamel margins were
      characterized (SEM) by prism fractures around restorations along with enamel
      chips and overhangs. These lesions were observed in about 30% of the samples.
      Dentin margins showed gaps along the dentin-bonding agents and fractures in the
      bonding agent/composite interface. Glass ionomers showed similar but fewer
      lesions both at enamel and dentin interfaces.

PMID- 9522698
TI  - Fracture resistance of endodontically-treated premolars adhesively restored.
AB  - PURPOSE: To investigate the cusp fracture resistance of endodontically treated
      teeth, adhesively restored with various materials. MATERIALS AND METHODS: MOD
      preparations and endodontic treatment was carried out on extracted sound
      maxillary premolars. The cavities were restored with the amalgam Valiant in
      combination with Superbond or Panavia bonding, the resin composites Z100,
      Herculite XRV or Clearfil RP with their respective bonding systems, Z100 in
      combination with the glass ionomers Ketac Fil, Fuji II and Vitremer, and Tetric
      in combination with Compoglass. Fracture resistance was measured by axial loading
      in an Instron testing machine. RESULTS: One of the restorative methods, resin
      composites in combination with dentin bonding systems in beveled MOD preparations
      rendered the tooth a cusp fracture resistance which did not differ significantly
      from that of sound natural teeth. Two other restorative methods, bonded amalgam
      and a sandwich of glass ionomer cement/resin composite in beveled preparations
      were significantly weaker in resisting cusp fracture than sound natural teeth,
      but still significantly stronger than the unrestored tooth with a MOD
      preparation. It was statistically apparent that several adhesive restorative
      systems could satisfactorily be used to restore teeth after endodontic therapy.

PMID- 9522699
TI  - Bond strength and interfacial morphology of adhesives to primary teeth dentin.
AB  - PURPOSES: To evaluate (1) the shear bond strength to the dentin of primary teeth
      and failure site of hydrophilic dentin bonding agents, (2) the interfacial
      micromorphology of these adhesives on primary teeth. MATERIALS AND METHODS:
      Seventy-six primary noncarious molars stored in distilled water were obtained.
      The teeth were cleaned with pumice and a rubber cup. The mesio-buccal surface of
      the teeth was ground flat with hand pressure with a series of SiC paper ending
      with the 600 grit to provide a uniform surface on superficial dentin to which the
      adhesives and resin composite could be applied. After preparing the dentin
      surface, the teeth were stored in distilled water for 48 hours. They were then
      rinsed and dried with compressed air and divided at random into four groups of 16
      specimens each: Group 1: Dentastic; Group 2: One-Step; Group 3: Prime & Bond 2.0;
      Group 4: Compoglass SCA. Z100 resin was used in all groups. All specimens were
      thermocycled (500x) and sheared in an Instron machine. After shear testing, the
      debonding sites of all samples were examined with a stereomicroscope and selected
      samples were also examined with the scanning electron microscope. Three
      additional samples per group were used to evaluate the resin adaptation to
      dentin. RESULTS: The results in MPa were: Dentastic 19.62 (4.67); One-Step 11.24
      (3.67), Prime & Bond 22.38 (6.47), Compoglass SCA 18.88 (4.04). ANOVA (P <
      0.0001) revealed that there was a significant difference between the groups. The
      Student-Newman-Keuls test (P < 0.05) showed no statistically significant
      difference between Dentastic, Prime & Bond and Compoglass SCA. However, these
      three groups were statistically significantly higher than One Step. In the
      Dentastic group, 14 of 16 samples revealed resin cohesive failure (resin
      fracture) while two of 16 displayed dentin cohesive failure (dentin fracture). In
      the One Step group, 15 samples failed at the resin and one sample showed dentin
      cohesive failure. In the Prime & Bond group, 12 specimens revealed resin cohesive
      failure while four displayed dentin cohesive failure. In the Compoglass SCA
      group, 13 samples had resin cohesive failures while three had dentin cohesive
      failures. All samples revealed an intimate adaptation to the dentin displaying
      resin tag formation.

PMID- 9522700
TI  - Enamel remineralization on teeth adjacent to Class II glass ionomer restorations.
AB  - PURPOSE: To examine the in vitro remineralization of incipient carious lesions on
      teeth adjacent interproximally to teeth with Class II glass ionomer cement
      restorations. MATERIALS AND METHODS: Artificial carious lesions were created at
      the contact area of 30 teeth. Ten teeth had Class II glass ionomer cement/resin
      composite restorations placed, 10 teeth had Class II glass ionomer silver cermet
      restorations placed and 10 teeth had Class II amalgam restorations placed.
      Sections 100 microns thick were obtained longitudinally through the caries sites
      and polarized photomicrographs were taken in imbibition media of water and
      Thoulet's (R.I. 1.41 and 1.47) solutions, representing 5%, 10% and 25% pore
      volume respectively. Varnish was placed on the section, leaving only the external
      section site exposed, then sections were situated back into the original tooth.
      The restored teeth were abutted to the carious tooth so that the restorations
      came into contact with the adjacent restoration. The specimens were placed into
      closed environments of artificial saliva for 14 days, then were photographed
      again under polarized light and areas of the carious lesions were quantitated.
      RESULTS: An ANOVA indicated significant variance in adjacent tooth
      remineralization, when comparing the experimental groups, in imbibition media of
      water (P < 0.05), Thoulet's 1.41 solution (P < 0.008) and Thoulet's 1.47 solution
      (P < 0.006). Duncan's multiple range test demonstrated the glass ionomer
      cement/resin composite group to have significantly greater decrease in pore
      volume (P < 0.05) than the amalgam control group in water imbibition media and
      Thoulet's 1.47 media. There was no statistically significant difference between
      the glass ionomer cement/resin composite and glass ionomer silver cermet groups
      in these two imbibition media. The glass ionomer cement/resin composite group
      demonstrated significantly more (P < 0.05) decrease in pore volume than both the
      glass ionomer silver cermet group and amalgam control group in Thoulet's 1.47
      imbibition media.

PMID- 9522702
TI  - Bleaching following porcelain veneers: clinical cases.
AB  - These clinical reports present two somewhat identical cases needing bleaching of
      the opposing teeth following placement of porcelain veneers. Using a new light
      activated power bleaching gel (Opalescence Xtra) eliminated color discrepancies
      between veneered and non-veneered teeth. In both cases ideal esthetic results
      were achieved.

PMID- 9522701
TI  - Effect of nail varnishes and petroleum jelly combinations on glass ionomer dye
      uptake.
AB  - PURPOSE: To evaluate the effectiveness of different brands of nail varnish alone
      or associated with petroleum jelly as surface protectors for glass ionomer
      cements by determining dye uptake spectrophotometrically. MATERIALS AND METHODS:
      Three hundred thirty six specimens, 3.0 mm in diameter and 1.0 mm thick, were
      made with Chelon-Fil (CF) and ChemFil II (CII) and divided into 14 groups for
      each material. Positive control (A) and negative control (B) specimens were not
      protected, while experimental specimens were protected with six brands of nail
      varnish used with and without petroleum jelly. The specimens were immersed in
      0.05% methylene blue solution 10 minutes after mixing except for negative control
      specimens that were immersed in deionized water. RESULTS: Dye uptake (microgram
      dye/restoration) for CF was: A = 11.3 +/- 3.1; B = 0.0 +/- 0.0 with varnish
      groups ranging from 0.6 to 2.5 and for CII: A = 12.4 +/- 2.5; B = 0.0 +/- 0.0
      with varnish groups ranging from 0.4 to 2.4. The data were analyzed by ANOVA. The
      dye uptake among the groups was not significantly different (P < 0.01), except
      for the control group (unprotected cements).

PMID- 9522703
TI  - Keeping ether in vogue. The role of Nathan Cooley Keep, M.D., D.M.D. in the
      history of etherization.

PMID- 9522704
TI  - A survey on the use of mouthguards and associated oral injuries in athletics.

PMID- 9522705
TI  - An evaluation of removable partial dentures: a retrospective study.
AB  - A 50% sample (N = 100) of all patients aged between 50-70 years at the time of
      treatment who received RPDs' were interviewed by telephone for 8-10 minutes. The
      questionnaires evaluated the subjects' denture experience, attitudes to dentures,
      and satisfaction with them. A large majority were satisfied with their RPD's but
      a higher proportion of women reported problems with mandibular RPD's. About one
      third of the group had not returned for recalls. Statistically significant
      relationships were found which suggested that subjects who were satisfied with
      their previous dentures were more likely to be satisfied with their replacements,
      and subjects who removed their RPD's to eat were likely to be dissatisfied with
      them.

PMID- 9522707
TI  - Opinion survey on dental assisting duties.

PMID- 9522706
TI  - "Care for Kids": Iowa's E.P.S.D.T. program. Early and periodic screening,
      diagnosis and treatment.

PMID- 9522708
TI  - Data Bank: Q & A.

PMID- 9522709
TI  - Results of the 1994 Iowa Oral Health Survey.

PMID- 9522710
TI  - Panavia/sandblasted resin bonded prostheses: a five year retrospective study.
AB  - The authors feel that this study suggests that the Panavia/sandblasted retention
      method, with its low debond rate, is a viable method for luting resin bonded
      prostheses. The authors wish to acknowledge the services of Ms. Jane Jakobsen
      (statistician) and Ms. Connie Norton (secretary) who made significant
      contributions to the completion of this article. Their help was much appreciated.

PMID- 9522711
TI  - Diabetes and the dental team.

PMID- 9522712
TI  - Etiology of cracked teeth: a review and proposal.
AB  - Factors in the etiology of the cracked or fractured tooth can be generally
      divided into three categories: tooth strength, magnitude of applied force, and
      control of applied force. Dental caries, restorations and endodontic procedures
      appear to play a major part in the etiology of most cracked or fractured teeth
      though sound teeth frequently are cracked or fractured. Tentative evidence
      indicates that females, who can apply less force, may crack more teeth than do
      males. Control of occlusal forces applied may be an overlooked factor. Drugs
      affecting proprioception and other sensory receptors modulating force and reflex
      should be evaluated as possible contributors to the etiology of cracked or
      fractured teeth.

PMID- 9522713
TI  - Diagnostic exercise. A radiopaque entity.

PMID- 9522714
TI  - Radiolucent entity of the anterior maxilla.

PMID- 9522715
TI  - Periodontal treatment options or implants? A discussion illustrated by four
      cases.

PMID- 9522716
TI  - Two cases of vertical root fracture.

PMID- 9522717
TI  - Pre-pubertal periodontitis: a case presentation.

PMID- 9522718
TI  - Determination of the critical size for non-healing defects in the mandibular bone
      of sheep. Part 1: A pilot study.

PMID- 9522719
TI  - The developing role of the hygienist in New Zealand: Part I.

PMID- 9522720
TI  - NZ National Certificate in Dental Hygiene: a review of the first graduates in
      1995.

PMID- 9522721
TI  - Calcifying fibroblastic granuloma. A case report.

PMID- 9522722
TI  - The cosmetic practice: building from the ground up.
AB  - Is this practice management, patient relations, public relations or simply
      marketing? The name is insignificant as long as one realizes what it is and how
      it can work for each and every one of us. Call it what you will: practice
      management, patient relations, etc. Simply stated, marketing is a systematic
      approach to practice growth which consists of analysis, development of a
      philosophy or focus, strategies, techniques, and skills. The elements involved
      include image, identity, environment, and communication, both verbal and
      nonverbal. Using a structured program that takes into consideration each of these
      elements will educate patients regarding quality care. It will provide patients
      with expanded services. It will give patients alternative esthetic options, and
      give them something to smile about. It will change any practice into a growing
      and thriving cosmetic practice. One picture is worth a thousand words. The
      practices that say "cosmetic dentistry" will succeed in the 1990s.

PMID- 9522723
TI  - Endodontics and the geriatric patient: is there a difference?

PMID- 9522725
TI  - Restoration of minimally invasive micropreparations with a compomer.

PMID- 9522724
TI  - Pediatric infection with the human immunodeficiency virus.
AB  - While rates of infection with the HIV virus are decreasing, the number of
      children infected continues to increase. There are multiple implications for the
      practicing pediatric dentist. Many of these children will seek or be referred by
      other health care providers for treatment of resulting oral pathology. Dentists
      must be prepared to provide dental services to the HIV-infected child.

PMID- 9522726
TI  - Resin bonding technology.

PMID- 9522727
TI  - The secrets to effective bonding.

PMID- 9522728
TI  - The National Practitioner Data Bank: is big brother watching you?

PMID- 9522729
TI  - Dental computing for the new millennium (or band-aids for dentists on the cutting
      edge).

PMID- 9522730
TI  - Dental caries and oral hygiene amongst 12-14 years old handicapped children of
      Bombay, India.
AB  - The present study was carried out to assess the oral health status of children
      suffering from different handicapping conditions studying in various schools of
      Bombay. A total of 593 handicapped children in the age group of 12-14 years were
      included in the study. The prevalence and severity of dental caries was found to
      be highest in the cerebral palsy group and lowest in the blind group. In general,
      in all the groups the decayed (D) component took predominance over the missing
      (M) and filled (F) components. Periodontal status was assessed using the CPITN
      and it was found that the bleeding & calculus components were higher than the
      healthy components in all the groups and almost all the children required
      treatment in the form of deep scaling and/or prophylaxis and oral hygiene
      instructions. The study confirmed the need of curative and preventive services
      towards these neglected children of the society.

PMID- 9522731
TI  - Assessment of puberty growth spurt in boys and girls--a dental radiographic
      method.
AB  - The first radiographic appearance of adductor sesamoid bone of thumb is
      considered reliable and is the most commonly used indicator of puberty growth
      spurt. The purpose of this study was to find out whether the tooth mineralization
      stage/stages were as reliable an indicator of puberty growth spurt as the
      adductor sesamoid bone. Puberty assessment has its necessary application in
      diagnosis, treatment planning of various malocclusions and in medico legal cases.
      The results indicated that a close relationship existed between tooth
      mineralization Stage G and appearance of the sesamoid bone. Hence it can be used
      in dentistry as an indicator for onset of puberty growth spurt via periapical or
      panoramic radiographs. The result of this study were not applicable to boys as
      the apical closure of these teeth had already occurred at the time of early
      radiographic appearance of the adductor sesamoid bone.

PMID- 9522732
TI  - An in vitro comparative evaluation of the tensile bond strength at the two
      interfaces of the sandwich technique.
AB  - This study was conducted to compare the tensile bond strength at the two
      interfaces of the "sandwich technique". 48 hours after the specimens were tested,
      using Hounsfield tensometer. Load was gradually applied on to the specimen till
      the bond at the interface failed. The load at which the bond failed was recorded
      and analysed for statistical significance. From the present study it can be
      concluded that the bond between glass ionomer and dentine is better than the bond
      between glass ionomer and composite resin.

PMID- 9522733
TI  - Physiological response to dental anxiety in children.
AB  - The study was conducted among 50 children in the age group of 8-9 yrs. to
      evaluate the anxiety producing dental procedures in the dental operatory viz.
      waiting at the reception area, examination in the dental chairs, scaling,
      polishing, cavity cutting, injection, extraction and post extraction period. The
      pulse rates were very high during local anaesthesia, extraction, waiting at
      reception and examination. A significant correlation was observed between the
      pulse rate and blood pressure.

PMID- 9522734
TI  - Dentin dysplasia--a case report.

PMID- 9522735
TI  - Oral candidal carriage in young insulin dependent diabetics.
AB  - Fifty patients with insulin-dependent diabetes mellitus (IDDM) in the age group
      of 5-20 years were assessed for oral candidal carriage state and other related
      oral manifestations. The control group showed 16% Candida carrier state, whereas
      the IDDM group showed 92% candida carrier state. The candidal count was
      significantly higher in the IDDM group. Other associated oral manifestations like
      dry mouth, burning sensation, and painful fissures were also observed in the IDDM
      subjects.

PMID- 9522736
TI  - Oral mucosal lesions in patients with acute leukemias and related disorders due
      to cytotoxic therapy.
AB  - Forty-seven children afflicted with acute leukemia were studied at the Tata
      Memorial Hospital Bombay to record the occurrence of oral manifestations prior to
      and during chemotherapy. Lymphadenopathy was the most frequent single finding
      suggestive of leukemia during head and neck examination. Gingival abnormalities,
      bleeding gums and oral mucosal pallor were the other findings on initial oral
      examination. Due to immunosuppression caused by the chemotherapy drugs oral
      mucosal ulcerations, uncontrolled herpes, candidiasis and pseudomoniasis were
      observed.

PMID- 9522737
TI  - Occlusal status and permanent teeth eruption in Libyan children.
AB  - The occlusal status was assessed in 2015 Libyan children. Angle class I was found
      to be the predominant type (94.5%), overbite relationship in the majority (50.6%)
      were within the incisal third. The mean overjet measurements ranged from 2 mm. to
      8 mm. Small proportion (13.4%) of the children examined were assessed to have a
      signs of crowding. Only 18.7% of the children were found to require orthodontic
      treatment. Eruption of permanent teeth was earlier in girls than in boys. The
      interval of rest between the mandibular lateral incisors and canines was 2.68
      years for boys and 2.76 years for girls.

PMID- 9522738
TI  - Formulation of a prediction chart for mixed dentition analysis.

PMID- 9522739
TI  - Keratins as markers in odontogenesis--an immunocytochemical experimental study in
      rats.
AB  - The expression and distribution of keratins within different layers of enamel
      organs of embryonic and neonatal rats studied by using indirect immunoperoxidase
      and immunofluorescent techniques in paraffin-embedded tissues employing specific
      antibodies revealed Keratin positivity in odontoblastic layer, oral epithelium
      and dental lamina in primitive stages; other odontogenic tissues showed negative
      reaction.

PMID- 9522741
TI  - An evaluation of pH changes of human dental plaque after oral rinsing of commonly
      prescribed syrup medications.
AB  - The study was carried out on 60 school going children (dft/DMFT 2-5) aged 8-13
      years randomly distributed into six age groups of ten subjects each. One group
      acted as a control in which subjects rinsed with 10% sucrose while in the other
      five groups, the subjects rinsed with 5 commonly prescribed syrup medications for
      10 seconds. Plaque samples were collected before rinsing and at 5,10,20,30 min.
      intervals post rinsing and plaque pH was measured extraorally. All the 5 groups
      showed drop in the plaque pH, similar to control group 10% sucrose solution, but
      not to the extent of critical pH (5.5).

PMID- 9522740
TI  - Study of microflora in well-nourished and mal-nourished children in relation to
      dental caries.
AB  - Forty-five children in the age group of 2-12 years comprising 20 well-nourished
      (W.N.), 20 malnourished (M.N.) (both groups having DMFS of > or = 5) and 5 caries
      free well nourished children (control group) were studied to find out the oral
      microflora in these groups S. mutans was present in 55%, 20% and 0% in W.N.,
      M.N., and control groups while S. Salivarius was isolated in 45%, 80% and 40% in
      the three groups respectively. There was no significant difference in the
      prevalence of Lactobacillus and C. albicans in the three groups. The correlation
      between means DMFS and the prevalence of S. mutans in W.N. and M.N. groups was
      highly significant (P < 0.001). Nutritional status including different grades of
      malnutrition had no significant bearing on the prevalence of micro-organisms
      isolated. The caries prevalence was higher in the W.N. group (P) while the
      gingival index was higher in M.N. group.

PMID- 9522742
TI  - Localised disturbances associated with primary teeth eruption.
AB  - The survey carried out on 201 infants of Calcutta aged 6-12 months to find out
      the localised disturbances associated with the eruption of the primary teeth, as
      judged through a questionnaire revealed that the most common disturbance was the
      inflammation of gums followed by flushing of cheeks, ulcers in mouth, cheek rash
      and eruption cyst.

PMID- 9522743
TI  - Evaluation of the change in the knowledge of community regarding infant dental
      care subsequent to intervention strategies through existing health manpower in
      rural areas of Haryana (India).
AB  - The knowledge about infant dental care (as a part of primary preventive
      programme) was delivered by the existing health team of CHC viz. medical doctors,
      multipurpose workers, health workers, Anganwadi workers (ICDS scheme), after due
      training from the dental experts, in the rural community of Raipur Rani
      (Haryana). The knowledge of community regarding infant dental care subsequent to
      intervention strategies when evaluated and compared to baseline values three
      years after intervention revealed that 72 percent of the community had the
      correct knowledge of prolonged breast/bottle feeding causing nursing bottle
      caries. 94 per cent had correct knowledge about harmful effects of thumb/finger
      sucking on teeth and jaw bones and 77 percent about harmful effects of mouth
      breathing. 98 percent of expecting mothers knew when to clean the gum pads and 62
      percent how to clean the gum pads in an infant. 100 percent of the expecting
      mothers had the correct knowledge that pacifiers should not be used in small
      children.

PMID- 9522744
TI  - Fluoride profiles of enamel following topical application of neutral and
      acidulated NaF solution using x-ray photoelectron spectroscopy (ESCA)--an in
      vitro study.
AB  - An in vitro analysis of fluoride in the surface enamel using x-ray photo-electron
      spectroscopy carried out on sound untreated teeth, sound teeth treated with
      neutral NaF and acidulated NaF and teeth with artificial caries treated with NaF
      and acidulated NaF revealed Ca/F ratio at surface and 360 degrees A as 0.140:1
      and 0.140:1; 0.636:1 and 0.192:1; 1.112:1 and 0.908:1. 1.2:1 and 1.289:1; 2.11:1
      and 1.87:1 respectively.

PMID- 9522745
TI  - Effect of a specially formulated remineralizing solution on the remineralizing
      capacity of saliva.
AB  - The present study was carried out to assess whether the remineralization of
      artificial caries like lesion by artificial saliva can be improved by daily 5
      minute treatment in a specially formulated remineralizing solution containing Ca,
      P, Zn, Sr, F. Extracted human premolars were dipped for 24 hours in artificial
      saliva and subsequently daily for 5 minutes in the remineralizing solution for 3
      weeks. Lesions were assessed using transverse microradiography, electron probe
      microanalysis (EPMA) and scanning electron microscope (SEM). The results showed
      that remineralization by specially formulated solutions repair the enamel lesion
      and enhances the salivary remineralizing potential.

PMID- 9522746
TI  - Oratest:--a simple, chair-side caries activity test.
AB  - Caries activity tests are an essential part of any programme concerned with the
      study or treatment of dental caries. Most of the caries activity tests require
      expensive kits or specially prepared media or facilities for incubation which
      limits their use in clinical practice. The present study sample consisted of
      twenty five children with dental caries and twenty five controls, free of caries,
      gingivitis and other oral ailments. The test is simple and consists of rinsing
      the mouth with 10 ml of sterile milk, 3 ml of which is mixed with 0.12 ml of 0.1%
      methylene blue dye and observed for colour change. The present study demonstrated
      the potential uses of this test in a pediatric dental clinic setup.

PMID- 9522748
TI  - Configuration of root canals in permanent mandibular first molars--an in vitro
      study.
AB  - The study attempts to show a number of variations in the root canal morphology of
      permanent mandibular first molar. The presence of variations increases the chance
      of failure of endodontic treatment. Knowledge about internal anatomy of the teeth
      is very essential for a favourable prognosis.

PMID- 9522747
TI  - A study of toothbrush contamination at different time intervals and comparative
      effectiveness of various disinfecting solutions in reducing toothbrush
      contamination.
AB  - Toothbrush contamination during the procedure of brushing was assessed at
      different time intervals of usage. A peak value of 100% contamination was found
      at 1 month interval. Hence, a method suggesting disinfection of the toothbrush
      was employed by comparing the effectiveness of various disinfecting solutions
      available in the market so that, the brush does not become a source of potential
      pathogens.

PMID- 9522749
TI  - Prevalence and severity of dental caries and oral hygiene status in rural and
      urban areas of Calcutta.
AB  - A study was carried out in urban Calcutta and rural Belur (outskirts of Calcutta)
      amongst 9600 children in the age group of 6 to 14 years. It was seen that the
      prevalence and severity of dental caries was higher among children in urban areas
      whereas the oral hygiene levels were poorer among children in rural areas. It was
      also observed that rate of dental caries increased with age. Organised efforts
      are a must to prevent and control dental caries before it takes its toll with
      disastrous results.

PMID- 9522750
TI  - Natal and neonatal teeth: a review of 50 cases.
AB  - 50 cases of natal and neonatal teeth were studied at Seth G. S. Medical College
      and K.E.M. Hospital in order to find out its most common location, sexual
      predilection, occurrence etc. The cases of natal and neonatal teeth usually
      report to the hospital due to difficulty in suckling, ulceration to the breast
      nipple and fear of aspiration of the teeth.

PMID- 9522751
TI  - Infant palatal obturator.
AB  - The occurrence of a congenital cleft palate greatly impedes the habituation of
      efficient deglutition of an infant, causing aspiration of fluids in the air
      passage which may lead to complications like bronchopneumonia and infection of
      the airway and lungs. Inadequate nourishment due to difficulty in feeding affects
      the health and acts as a stumbling block in the milestones of normal development.
      Severe nutritional deficiencies further complicate surgical closure at the right
      time. A palatal obturator given to the infant effectively separates the oral
      cavity from the nasal cavity and is of great help in feeding till the defect can
      be surgically repaired.

PMID- 9522752
TI  - Combined effect of carbon-dioxide laser and neutral 2% NaF on acid resistance of
      human tooth enamel.
AB  - Specimens of human enamel were treated topically with 2% sodium fluoride solution
      before and after laser irradiation. The samples were examined using wet chemical
      analysis and SEM. The results showed that samples treated with neutral 2% NaF
      after irradiation caused a remarkable increase in acid resistance of the enamel,
      while samples treated with neutral 2% NaF before irradiation showed a lesser
      effect. The results were consistent with observations made by using wet chemical
      analysis and SEM findings.

PMID- 9522753
TI  - The effect of carbon dioxide laser on acid resistance of human tooth enamel: an
      evaluation by wet chemical analysis and scanning electron microscopy.
AB  - The use of the laser in improving acid resistance of tooth enamel has captured
      the imagination of most researchers. Man's susceptibility to dental caries
      presents itself as one of the most complicated problems to solve. The carbon
      dioxide laser at a wavelength of 10.6 microns is highly efficient for dental
      purposes as this wavelength is close to optimum absorption of dental enamel. A
      study was carried out using a pulsed carbon dioxide laser to find the effects of
      laser beam on human tooth enamel in an energy range of 2-20 J/cm2 at a pulse rate
      of 5 Hz. The effective resistance to acid was determined by wet chemical analysis
      whereas superficial changes seen on the surface were determined using the
      scanning electron microscope.

PMID- 9522754
TI  - Capillary hemangioma--report of a case.
AB  - A ten-year-old girl was referred for the management of a recurrent lobulated mass
      present in the upper anterior region. Histopathological investigations were
      suggestive of capillary hemangioma. Surgical excision of the lesion was performed
      and postoperative recovery was uneventful.

PMID- 9522755
TI  - Clinical and radiological evaluation of zinc oxide-eugenol and Maisto's paste as
      obturating materials in infected primary teeth--nine months study.
AB  - The present study, performed in-vivo, included 30 infected primary teeth in 26
      children in the age group of 3-8 years. The purpose of this study was to compare
      the efficacy of two obturating materials, zinc oxide-eugenol and Maisto's paste,
      in infected primary teeth. 30 teeth were divided into two groups of 15 teeth.
      Teeth in Group I were obturated using zinc oxide-eugenol and those in Group II
      were obturated using Maisto's paste. On clinical evaluation, teeth obturated with
      Maisto's paste showed 100% success. Five teeth that were overfilled with Maisto's
      paste showed complete resorption of excess material within 3 months while the two
      teeth overfilled with zinc oxide-eugenol showed incomplete resorption of the
      excess material even after 9 months. Zinc oxide-eugenol treated cases showed only
      26.7% bone regeneration while in case of Maisto's paste, it was 93%. Complete
      healing of the inter-radicular pathology was seen with Maisto's paste. However,
      the pathology was present in 40% of the zinc oxide-eugenol treated teeth even
      after 9 months. Maisto's paste was thus seen to be superior to zinc oxide-eugenol
      both in clinical as well as radiological evaluation, done over a period of 9
      months in relation to bone regeneration, healing of inter-radicular pathology and
      resorption of excess material.

PMID- 9522756
TI  - Sagittal craniofacial morphology in repaired unilateral and bilateral complete
      cleft lip and palate cases.
AB  - Fifty repaired complete cleft lip and palate cases (38 UCLP and 12 BCLP) in the
      age of 6 to 14 years were evaluated for sagittal craniofacial morphology using
      lateral cephalograms. A total of twenty three measurements (19 angular and 4
      linear) were used in the analysis to represent a comprehensive pattern of dento
      craniofacial morphology. The results of comparison between UCLP and BCLP revealed
      differences for only the skeletodental and interincisor sagittal relationship
      (greater retroclination in BCLP group).

PMID- 9522757
TI  - Dentigerous cyst with inflammatory etiology from a deciduous predecessor--report
      of a case.
AB  - Dentigerous cysts arising from overlying infected predecessor teeth are very
      rare. This report describes one such case where extraction of the infected
      deciduous tooth with marsupialization led to the eruption of the premolar.
      Periodic radiographic evaluation is required to note and prevent recurrence and
      other serious complications arising from these cysts.

PMID- 9522758
TI  - Effect of 4-META adhesive on bond strength and marginal seal of amalgam
      restorations and repairs--an in vitro study.
AB  - Amalgam remains unchallenged as a posterior restorative material. But its
      inability to bond to the teeth leads to some amount of microleakage at the
      restoration-tooth interface with associated problems such as post operative
      sensitivity, pulpal complications etc. Also a broken amalgam restoration requires
      replacement which will further weaken the tooth structure. Recently, 4-META has
      been introduced which can graft amalgam and composite to enamel, dentin and old
      amalgam restorations. In this study, the bonding and marginal sealing abilities
      of 4-META was assessed both at the tooth-amalgam interface and old amalgam fresh
      amalgam interface.

PMID- 9522759
TI  - Evaluation of fluoride uptake by enamel in children from fluoride dentifrices.
AB  - Fluoride dentifrices are well accepted for their caries preventive effects.
      Although it is generally accepted that the presence of fluoride in the enamel
      protects teeth against carious attack, at the same time, there is some concern
      that ingestion of fluoride from toothpastes may substantially contribute to the
      total intake of this element. The present study was undertaken to clinically
      evaluate the fluoride uptake by human enamel after the use of lower
      concentrations of fluoride dentifrices and compare their potency to higher
      concentration in increasing the uptake of fluoride by enamel. Enamel biopsy was
      conducted on first permanent molars of 100 school children, aged 6-8 years before
      brushing and at intervals of one hour, 3 weeks, 6 weeks and 12 weeks following
      brushing with different concentrations of fluoride dentifrices. The fluoride
      content of the enamel biopsy samples were estimated using the Orion
      microprocessor ion analyser and by taking into consideration the enamel biopsy
      mass and depth of the etch. The results of the present study suggest that low
      fluoride concentration dentifrices provide similar fluoride uptake by enamel when
      compared with that of higher concentrations.

PMID- 9522760
TI  - Surface treatment of enamel with laser--a potential alternative for acid etching-
      an in vitro study.
AB  - An in-vitro study was carried out on 80 human premolars to study the use of
      Nd:YAG laser as a potential alternative for acid etching in the surface treatment
      of enamel prior to sealant application. The determination of bond strength using
      Universal Testing Machine, Model 1011 and marginal leakage using the
      spectrophotometric dye recovery method showed no statistically significant
      difference between the groups with laser and acid surface treatments. But, there
      was a significantly lower bond strength and increased dye penetration in the
      group with no surface treatment. Scanning electron microscopic study of the
      interface between sealant and enamel surface of the acid and laser treated
      specimens was also carried out.

PMID- 9522761
TI  - The comparative evaluation of release profiles of aluminium, fluoride, sodium and
      strontium by resin modified and conventional glass polyalkenoate cements in
      neutral and acidic medium--an in vitro study.
AB  - The present study was carried out to evaluate the Al, F, Na and Sr release
      profiles of conventional and resin modified glass polyalkenoate cements in
      neutral (deionized water) and acidic medium (lactic acid). Twelve pellets of each
      material were prepared under standardised conditions and were immersed in their
      respective solutions for a study period of 90 days. Fluoride analysis was carried
      out by Orion Electrode and the other elemental analysis were done by Atomic
      Absorption Spectrophotometer. Statistical analysis revealed no significant
      difference in the Al, F and Na release profiles between the two materials in both
      neutral and acidic media.

PMID- 9522762
TI  - Doomed angels--a case report.
AB  - A three year old female child was brought to the Department of Pedodontics,
      Dental College, Thiruvananthapuram with a greyish white papillomatous lesion
      involving a large area on the buccal mucosa. VDRL was positive for the little
      girl as well as her father and was positive in low concentrations for her one
      month-old sister as well as her mother.

PMID- 9522763
TI  - A dermatoglyphic predictive and comparative study of Class I, Class II, div. 1,
      div.2 and Class III malocclusions.
AB  - A study was conducted using dermatoglyphics to predict and compare Class I, Class
      II, div. 1, div.2 and Class III malocclusions. A total of 96 subjects were
      divided into 3 malocclusion groups, i.e. Class I (control group), Class II,
      div.1, div.2 and Class III (experimental group) in the ages of 12-14 years. The
      dermatoglyphic findings revealed that the craniofacial Class II, div. 1, div.2
      pattern was associated with increased frequency of arches and ulnar loops and
      decreased frequency of whorls, whereas in Class III, there was an increased
      frequency of arches and radial loops with decreased frequency of ulnar loops. In
      predicting Class III malocclusion, based on frequency of arches, the sensitivity
      values were found to be higher and more reliable than the sensitivity values of
      Class II, div.1 and div.2 malocclusion.

PMID- 9522764
TI  - Etching of young permanent teeth with acid gel--a comparison between the effect
      of 15 seconds & 60 seconds of etching.
AB  - The purpose of present study was to compare the effect of 15 seconds & 60 seconds
      of etching of young permanent teeth in vitro with 50% phosphoric acid gel using
      scanning electron microscope. 25 pairs of enamel surfaces selected for the study
      were divided into 3 experimental groups. The control group consisted of unetched
      enamel surfaces. In Group II, the effect of 50% phosphoric acid gel was compared
      with 37% phosphoric acid solution for 15 seconds whereas in group III, the effect
      of 15 seconds & 60 seconds of etching with 50% phosphoric acid gel was compared.
      The degree of etching pattern was evaluated by using scoring pattern from 1-3.
      Results showed no significant difference between the etching pattern obtained
      with the use of 37% solution and 50% gel for 15 seconds. But it was observed that
      etching with 50% for 15 seconds resulted in equal or even an enhanced etching
      pattern as compared to the pattern obtained in 60 seconds with 50% phosphoric
      acid gel.

PMID- 9522765
TI  - Arteriovenous malformation of the mandible--report of a case.
AB  - An eight-year-old girl was referred for the management of recurrent bleeding from
      the lower, left gingival region and a diffused swelling on the left side of her
      face. Doppler study and carotid angiogram were suggestive of an arteriovenous
      malformation. Segmental mandibular resection was performed after ligation of the
      left external carotid artery. Post-operative period was uneventful and there has
      been no recurrence of the lesion till date.

PMID- 9522766
TI  - Complex odontome in deciduous dentition.
AB  - A three-year-old boy reported to the Dept. of Pedodontics with the complaint of
      swelling in the lower left side of the mouth. The radiographic and histologic
      study revealed the case to be a complex odontome which is rare in deciduous
      dentition.

PMID- 9522767
TI  - Bilaterally fused primary mandibular incisors--a case report.
AB  - Fusion of teeth results from abnormal events in the embryologic development of
      teeth. In most cases the clinical and radiological findings allow only a
      presumptive diagnosis to be established since the specific terminology described
      refers to the etiology of the process, which often cannot be established. An
      unusual case of bilateral fusion in primary mandibular incisor region in a four
      year-old boy is reported.

PMID- 9522768
TI  - Evaluation of an alum containing mouthrinse on plaque and gingivitis inhibition
      over 2 weeks of supervised use.
AB  - The present study was carried out on 40 municipal school children in the age
      group of 12-14 years to evaluate the effectiveness of daily supervised rinsing
      with specially formulated alum containing mouthrinse on plaque and gingivitis
      inhibition. The results of this 2 week study demonstrate that a mouthrinse
      containing 0.02 M Aluminium has significant effect on plaque inhibition. There
      was a reduction in gingivitis but it was not significant statistically.

PMID- 9522769
TI  - Dentistry: health care that works. A special report on national health system
      reform for Tennessee dentists.

PMID- 9522770
TI  - The Swiss heroin trials: testing alternative approaches.

PMID- 9522771
TI  - Deaths related to intrapartum asphyxia.

PMID- 9522772
TI  - Subcutaneous apomorphine in Parkinson's disease.

PMID- 9522773
TI  - Communication among health professionals.

PMID- 9522774
TI  - New government, same narrow vision.

PMID- 9522775
TI  - Lessons of a hip failure.

PMID- 9522777
TI  - Wisheart begins to give evidence at GMC.

PMID- 9522776
TI  - Short course of zidovudine cuts transmission of HIV.

PMID- 9522778
TI  - Doctor admits research fraud.

PMID- 9522779
TI  - Tissue trade in Hungary is investigated.

PMID- 9522782
TI  - Warning issued over hip implants.

PMID- 9522780
TI  - Marketing of antipsychotic drugs attacked.

PMID- 9522783
TI  - Inquiry ordered into transfer of the frail elderly.

PMID- 9522785
TI  - Commentary: identifying the correct risks in diagnosis.

PMID- 9522784
TI  - Population based study of risk factors for underdiagnosis of asthma in
      adolescence: Odense schoolchild study.
AB  - OBJECTIVE: To describe factors related to underdiagnosis of asthma in
      adolescence. DESIGN: Subgroup analysis in a population based cohort study.
      SETTING: Odense municipality, Denmark. SUBJECTS: 495 schoolchildren aged 12 to 15
      years were selected from a cohort of 1369 children investigated 3 years earlier.
      Selection was done by randomisation (n = 292) and by a history indicating allergy
      or asthma-like symptoms in subject or family (n = 203). MAIN OUTCOME MEASURES:
      Undiagnosed asthma defined as coexistence of asthma-like symptoms and one or more
      obstructive airway abnormalities (low ratio of forced expiratory volume in 1
      second to forced vital capacity, hyperresponsiveness to methacholine or exercise,
      or peak flow hypervariability) in the absence of physician diagnosed asthma. Risk
      factors (odds ratios) for underdiagnosis. RESULTS: Undiagnosed asthma comprised
      about one third of all asthma identified. Underdiagnosis was independently
      associated with low physical activity, high body mass, serious family problems,
      passive smoking, and the absence of rhinitis. Girls were overrepresented among
      undiagnosed patients with asthma (69%) and underrepresented among diagnosed
      patients (33%). Among the risk factors identified, low physical activity and
      problems in the family were independently associated with female sex. The major
      symptom among those undiagnosed was cough (58%), whereas wheezing (35%) or
      breathing trouble (50%) was reported less frequently than among those diagnosed.
      Less than one third of those undiagnosed had reported their symptoms to a doctor.
      CONCLUSIONS: Asthma, as defined by combined symptoms and test criteria, was
      seriously underdiagnosed among adolescents. Underdiagnosis was most prevalent
      among girls and was associated with a low tendency to report symptoms and with
      several independent risk factors that may help identification of previously
      undiagnosed asthmatic patients.

PMID- 9522786
TI  - Commentary: improving the diagnostic rate in asthma: a community issue.

PMID- 9522787
TI  - Numbers of deaths related to intrapartum asphyxia and timing of birth in all
      Wales perinatal survey, 1993-5.
AB  - OBJECTIVES: To investigate the relation between the timing of birth and the
      occurrence of death related to an intrapartum event. DESIGN: Analysis of 107,206
      births to Welsh residents in 1993-5, including 608 cases of stillbirth and 407 of
      neonatal death identified in the all Wales perinatal survey, the cause of death
      classified with the clinicopathological system. SUBJECTS: 79 normally formed
      babies stillborn or who died in the neonatal period, birth weight > 1499 g, for
      whom cause of death was related to an intrapartum event. MAIN OUTCOME MEASURES:
      Relative risk of death due to an intrapartum event according to the hour, day,
      and month of birth. RESULTS: Mortality was higher in babies born between 9.00 pm
      and 8.59 am than in those born between 9.00 am and 8.59 pm; relative risk (95%
      confidence interval) 2.18 (1.37 to 3.47). July and August births also had a
      higher death rate than births in other months; relative risk 1.99 (1.23 to 3.23).
      Weekened births had a higher death rate but it was not significant. CONCLUSIONS:
      The excess of deaths at night and during months when annual leave is popular may
      indicate an overreliance on inexperienced staff at these times. Errors of
      judgement may also be related to physical and mental fatigue, demanding a more
      disciplined systematic approach at night. Mistakes may be ameliorated by
      increasing shiftwork, but shifts should be carefully designed to avoid undue
      disruption of circardian rhythms. In addition, greater supervision by senior
      staff may be required at night and during summer months.

PMID- 9522788
TI  - Effectiveness of screening older people for impaired vision in community setting:
      systematic review of evidence from randomised controlled trials.
AB  - OBJECTIVE: To assess whether population screening for impaired vision among older
      people in the community leads to improvements in vision. DESIGN: Systematic
      review of randomised controlled trials of population screening in the community
      that included any assessment of vision or visual function with at least 6 months'
      follow up. SUBJECTS: Adults aged 65 or over. MAIN OUTCOME MEASURE: Proportions
      with visual impairment in intervention and control groups with any method of
      assessing visual impairment. RESULTS: There were no trials that primarily
      assessed visual screening. Outcome data on vision were available for 3494 people
      in five trials of multiphasic assessment. All the trials used self reported
      measures for vision impairment, both as screening tools and as outcome measures.
      The inclusion of a visual screening component in the assessment did not result in
      improvements in self reported visual problems (pooled odds ratio 1.04:95%
      confidence interval 0.89 to 1.22). A small reduction (11%) in the number of older
      people with self reported visual problems cannot be excluded. CONCLUSIONS:
      Screening of asymptomatic older people in the community is not justified on
      present evidence. Visual impairment in this age group can usually be reduced with
      treatment. It is unclear why no benefit was seen. Further work is needed to
      clarify what interventions are appropriate for older people with unreported
      impairment of vision.

PMID- 9522789
TI  - Association of glutamine 27 polymorphism of beta 2 adrenoceptor with reported
      childhood asthma: population based study.

PMID- 9522790
TI  - Parental history of gastric or duodenal ulcer and prevalence of Helicobacter
      pylori infection in preschool children: population based study.

PMID- 9522791
TI  - Relation of aplastic anaemia to use of chloramphenicol eye drops in two
      international case-control studies.

PMID- 9522792
TI  - Risk of serious haematological toxicity with use of chloramphenicol eye drops in
      a British general practice database.

PMID- 9522793
TI  - Effect of asthma and its treatment on growth: four year follow up of cohort of
      children from general practices in Tayside, Scotland.
AB  - OBJECTIVE: To investigate whether asthma or its treatment impairs children's
      growth, after allowing for socioeconomic group. DESIGN: 4 year follow up of a
      cohort of children aged 1-15. SETTING: 12 general practices in the Tayside region
      of Scotland. SUBJECTS: 3347 children with asthma or features suggestive of asthma
      registered with the general practices. MAIN OUTCOME MEASURES: Height and weight
      standard deviation scores. RESULTS: Children who lived in areas of social
      deprivation (assessed by postcode) had lower height and weight than their
      contemporaries (mean standard deviation score -0.26 (SD 1.02) and -0.18 (1.15)
      respectively, P < 0.001 for both). Children who were receiving > or = 400
      micrograms daily of inhaled steroids and who were attending both hospital and
      general practice for asthma care had lower height and weight than average,
      independent of the effect of deprivation (mean standard deviation score -0.62
      (1.01), P = 0.002, for height and -0.58 (0.94), P = 0.005, for weight). Children
      receiving high doses of inhaled corticosteroids also showed lower growth rates
      (mean change in standard deviation score -0.19 (0.51), P = 0.003). However, no
      other children with asthma showed growth impairment. CONCLUSION: Most children
      with asthma were of normal height and weight and had normal growth rates.
      However, children receiving high doses of inhaled steroids and requiring both
      general practice and hospital services had a significant reduction in their
      stature. This effect was independent from but smaller than the effect of
      socioeconomic group on stature.

PMID- 9522794
TI  - Communication behaviours in a hospital setting: an observational study.
AB  - OBJECTIVE: An exploratory study to identify patterns of communication behaviour
      among hospital based healthcare workers. DESIGN: Non-participatory, qualitative
      observational study. SETTING: British district general hospital. SUBJECTS: Eight
      doctors and two nurses. RESULTS: Communication behaviours resulted in an
      interruptive workplace, which seemed to contribute to inefficiency in work
      practice. Medical staff generated twice as many interruptions via telephone and
      paging systems as they received. Hypothesised causes for this level of
      interruption include a bias by staff to interruptive communication methods, a
      tendency to seek information from colleagues in preference to printed materials,
      and poor provision of information in support of contacting individuals in
      specific roles. Staff were observed to infer the intention of messages based on
      insufficient information, and clinical teams demonstrated complex communication
      patterns, which could lead to inefficiency. CONCLUSION: The results suggest a
      number of improvements to processes or technologies. Staff may need instruction
      in appropriate use of communication facilities. Further, excessive emphasis on
      information technology may be misguided since much may be gained by supporting
      information exchange through communication technology. Voicemail and email with
      acknowledgment, mobile communication, improved support for role based contact,
      and message screening may be beneficial in the hospital environment.

PMID- 9522796
TI  - Hypopituitarism after coronary artery bypass grafting.

PMID- 9522795
TI  - Update on male erectile dysfunction.

PMID- 9522797
TI  - Commentary: hypoadrenalism should also be considered in cases of persistent
      hyponatraemia.

PMID- 9522798
TI  - ABC of allergies. Diagnosing allergy.

PMID- 9522799
TI  - Interpreting treatment effects in randomised trials.

PMID- 9522800
TI  - The new genetics. Psychological responses to genetic testing.

PMID- 9522801
TI  - Maintaining standards in British and Canadian medicine: the developing role of
      the regulatory body.

PMID- 9522802
TI  - Prophylaxis after occupational exposure to HIV. Portsmouth has 24 hour hotline
      staffed by nurse specialists.

PMID- 9522803
TI  - Prophylaxis after occupational exposure to HIV. Follow up may have to be for
      longer than six months.

PMID- 9522804
TI  - Prophylaxis after occupational exposure to HIV. Register of cases of occupational
      exposure exists.

PMID- 9522805
TI  - Prophylaxis after occupational exposure to HIV. "Source testing" should be
      allowed.

PMID- 9522806
TI  - Prophylaxis after occupational exposure to HIV. Universal precautions should be
      used during all surgical procedures.

PMID- 9522807
TI  - Substitution of another opioid for morphine may be useful for pain control.

PMID- 9522808
TI  - Studies of drugs in epilepsy cited by author are not evidence based.

PMID- 9522809
TI  - Search for evidence of effective health promotion. Quantitative outcome
      evaluation with qualitative process evaluation is best.

PMID- 9522810
TI  - Search for evidence of effective health promotion. Systematic reviews include
      studies other than randomised controlled trials.

PMID- 9522811
TI  - Debate is needed over who provides drug treatment in attention deficit
      hyperactivity disorder.

PMID- 9522812
TI  - Community based heart health promotion project in England. Self reporting
      overestimates smoking cessation rates.

PMID- 9522813
TI  - Community based heart health promotion project in England. Authors conclusions
      are unjustified and misleading.

PMID- 9522814
TI  - Bus shelters in photograph, showing drug adverts, were replaced long ago.

PMID- 9522815
TI  - Consultants could give patients a letter summarising their consultation.

PMID- 9522816
TI  - Self regulation is necessary in war on drugs.

PMID- 9522817
TI  - Vulval Pain Society provides information on vulval symptoms.

PMID- 9522819
TI  - Several factors were not considered in study of increase in hay fever and eczema.

PMID- 9522818
TI  - Weight loss will be much faster in lean than in obese hunger strikers.

PMID- 9522820
TI  - Royal colleges need modernisation.

PMID- 9522821
TI  - Historical perspective on nutritional support of cancer patients.
AB  - Initially, total parenteral nutrition (TPN) was not used in cancer patients
      because of the fear of sepsis and the potential for stimulation of tumor growth.
      It was used first in cancer patients who had failed all attempts at enteral
      nutrition and in whom adequate anticancer therapy would have been otherwise
      impossible. TPN candidates today remain patients with responsive tumors who
      cannot tolerate the toxicity of cancer therapy because they are malnourished.

PMID- 9522823
TI  - The politics of addiction: status of the tobacco settlement.
AB  - The enactment of an effective national tobacco control policy is a needed first
      step toward reducing smoking, controlling the tobacco industry, and significantly
      reducing tobacco-related disease and death. Dr. Seffrin, Chief Executive Officer
      of the American Cancer Society, outlines the critical public health measures that
      the ACS is working to see included in comprehensive federal tobacco control
      legislation.

PMID- 9522822
TI  - Nutritional support of the cancer patient.
AB  - Malnutrition, a common problem in cancer patients, adversely affects survival and
      quality of life. It results from several factors that alter nutritional intake
      and cause massive metabolic disturbances. Anticancer therapies may compound the
      malnutrition. Optimal nutrition improves therapeutic modalities and the clinical
      course and outcome. Oral nutrition should be used whenever possible; in patients
      unable to ingest adequate amounts orally, enteral and parenteral feedings are
      safe and effective.

PMID- 9522824
TI  - Standards for diagnosis and management of invasive breast carcinoma. American
      College of Radiology. American College of Surgeons. College of American
      Pathologists. Society of Surgical Oncology.
AB  - Because knowledge has advanced in several fields related to the treatment of
      early breast cancer, revising the landmark 1992 standards for breast-conservation
      treatment by these four organizations is appropriate. The current report reviews
      and summarizes the literature and describes the selection and evaluation of
      patients, the technical aspects of surgical treatment and irradiation, follow-up
      care, and areas for further research.

PMID- 9522826
TI  - Primary care management of benign prostatic hyperplasia.

PMID- 9522825
TI  - Standards for diagnosis and management of ductal carcinoma in situ (DCIS) of the
      breast. American College of Radiology. American College of Surgeons. College of
      American Pathologists. Society of Surgical Oncology.
AB  - A sufficient body of knowledge has developed about ductal carcinoma in situ of
      the breast to warrant a separate report on standards of care for women with this
      disease. This consensus report by these four organizations discusses evaluation
      of the patient, selection of treatment, technical aspects of diagnostic biopsy
      and definitive local excision, pathologic evaluation, radiation therapy
      considerations, follow-up care recommendations, and questions for future
      research.

PMID- 9522827
TI  - Antibiotics and myasthenia gravis.

PMID- 9522828
TI  - Prophylaxis for acute mountain sickness.

PMID- 9522829
TI  - Thyrotoxic hypokalemic periodic paralysis.

PMID- 9522830
TI  - Cardiomyopathy with a pulse of 100.

PMID- 9522831
TI  - Case in point. Chest-wall lipoma.

PMID- 9522832
TI  - Unexplained weight loss and arterial thromboses.

PMID- 9522833
TI  - The genetics of obesity.
AB  - Five genes have been identified, each capable of causing obesity in mice and each
      with a human homologue. One of them codes for a signal expressed by adipose
      tissue, and another for the signal's brain receptor. The rest reveal brain
      pathways probably downstream from the receptor. Together, the genes offer
      glimpses of an intricate system that defends adipose stores--and in some persons
      maintains an unhealthful set-point.

PMID- 9522834
TI  - Arthropathy in hemochromatosis.
AB  - Arthritis may be the presenting manifestation of iron overload. The
      metacarpophalangeal joints are often involved, producing a condition that
      resembles osteoarthritis but at a site typically affected by rheumatoid
      arthritis. Treatment of the arthritis is often disappointing, but identification
      of the underlying disease permits institution of life-saving phlebotomy therapy.

PMID- 9522835
TI  - Pulmonary edema in a young man after postoperative extubation.

PMID- 9522836
TI  - Atypical ketoacidosis in type 2 diabetes.
AB  - The clinical stereotype that divides diabetic patients into those who are thin
      and need insulin and those who are obese and do not need insulin can be
      misleading. Some patients with type 2 diabetes present with ketoacidosis and
      require insulin treatment. Many of them can be weaned from insulin, although they
      may require hypoglycemic therapy.

PMID- 9522837
TI  - Evaluation and treatment of wrist and hand pain.

PMID- 9522838
TI  - Leadership in the changing health care world.

PMID- 9522839
TI  - Fatigue and abdominal fullness in a 36-year-old woman.

PMID- 9522840
TI  - Progress in the management of Alzheimer's disease.
AB  - As the population of the United States continues to age, age-related diseases
      such as Alzheimer's, the most common form of dementia, pose an increasing
      clinical challenge. The diagnosis of Alzheimer's disease hinges on the evaluation
      of cognitive function. Management options are expanding and include new
      cholinesterase inhibitors, cholinergic agonists, antioxidants, monoamine oxidase
      inhibitors, and estrogen.

PMID- 9522841
TI  - Acute coronary syndromes: 1. The platelet's role.
AB  - Platelets play key physiologic roles in the hemostatic response to vascular
      injury. But thrombi that form in the absence of vessel wall damage may either
      disrupt or completely block blood flow. A better understanding of platelet
      pathophysiology promises to lead to improved therapy of myocardial infarction,
      unstable angina, and related syndromes.

PMID- 9522842
TI  - Evidence-based medicine at the Agency for Health Care Policy and Research.

PMID- 9522843
TI  - Health and major resource developments in Papua New Guinea: pot of gold or can of
      worms at the end of the rainbow?

PMID- 9522844
TI  - Infant mortality in a deprived area of Papua New Guinea: priorities for antenatal
      services and health education.
AB  - This cross-sectional study of women was conducted in a deprived area of Papua New
      Guinea with an estimated infant mortality rate of 133/1000 live births. Mortality
      patterns derived from birth histories showed that neonatal deaths contribute
      proportionally more to infant mortality than postneonatal deaths, emphasizing the
      need for better care at delivery. To examine possible mechanisms for
      intervention, pregnant women were interviewed to determine patterns of antenatal
      clinic use, antimalarial drugs and micronutrient supplements given, and how much
      the women smoked. The results showed that the health system was failing to
      implement current routine supplementation and prophylaxis regimens, and that
      there was a need to revise national guidelines. A large proportion of pregnant
      women smoked during pregnancy, and this behaviour could be a target for future
      public health campaigns and health worker promotion advice to women.

PMID- 9522845
TI  - How should very low birthweight babies best be managed in Papua New Guinea?
AB  - Short-term outcome in very low birthweight babies has never been closely examined
      in Papua New Guinea. A cohort of neonates born over a year at Port Moresby
      General Hospital was followed from birth to death or discharge. Intrauterine
      growth retardation was an important contributor to low birthweight. Simple,
      inexpensive care resulted in respectable survival figures. Improving antenatal
      surveillance will have much more impact in reducing mortality in this group in
      the future than trying to emulate sophisticated and costly western neonatal care.

PMID- 9522846
TI  - Resistance of Plasmodium falciparum malaria to amodiaquine, chloroquine and
      quinine in the Madang Province of Papua New Guinea, 1990-1993.
AB  - The in vivo response of Plasmodium falciparum parasites to amodiaquine or
      chloroquine was assessed in children with symptomatic malaria attending different
      health facilities in the Madang area. Among the 27 subjects who were completely
      followed up, 4 (15%) were infected with parasites fully susceptible and 23 (85%)
      with parasites exhibiting some degree of resistance. Out of the latter group, 52%
      were of RI level, 26% RII and 22% RIII. 14 subjects out of 42 (33%) failed to
      clear their parasitaemia by day 7 and 92 out of 134 (69%) had persistent or
      recrudescent parasitaemia at day 21. The level of in vivo resistance was similar
      for amodiaquine and chloroquine. 86% of the isolates tested in vitro showed
      resistance to amodiaquine, 86% to chloroquine and 7% to quinine. In ten years the
      prevalence of resistant isolates in vivo has increased from 47% to 85%. Of more
      concern is the shift from RI level of resistance to RII and RIII: the proportion
      of resistant strains that were RI dropped from 90% to 52% over the ten-year
      period. To determine if the standard antimalarial regimens are still appropriate,
      there is a need not only to assess the level of parasite resistance but also the
      prevalence of treatment failure in different parts of Papua New Guinea.

PMID- 9522847
TI  - Women in the central highlands of Irian Jaya, Indonesia.
AB  - The weight, height and mid-upper-arm circumference (MUAC) were measured in 159
      women of reproductive age between June and November 1991 in four remote valleys
      in the Eastern Central Highlands of Irian Jaya, Indonesia. The average weight was
      42.3 +/- 5.2 kg and 26% weighed less than 40 kg. The average height was 141.3 +/-
      9.1 cm and 30% were shorter than 140 cm. By the MUAC measurement, the nutritional
      status was considered to be inadequate (MUAC less than 23 cm) in 58% of the
      women. 8% of the women were observed to be visibly pregnant and 43% were
      lactating. In the same period 112 women in the Yamil valley were visited at home.
      They had given birth to 331 children, of whom 83 had died before the age of five
      years, i.e. a child mortality rate of 251 per 1000 births. Nearly half of the
      mortality (45%) occurred shortly after birth.

PMID- 9522848
TI  - Profile of blood donors in Port Moresby.
AB  - A record analysis study was conducted on blood donors in the greater Port Moresby
      area to determine the trend in the number of blood donations and the profile of
      donors between 1985 and 1994. There was no significant change in the donation
      trend between 1985-1989 and 1990-1994. While there were no changes in the age
      distribution between these two periods, there were significant increases in
      female donors (from 17% to 25%) and new donors (47% to 54%) during 1990-1994. The
      study data show that there has been a problem in the retention of donors in the
      greater Port Moresby area during the 1990-1994 period.

PMID- 9522849
TI  - Papua New Guinea Red Cross Blood Transfusion Service: present status and future
      considerations.
AB  - About 28,000 units of blood are collected per annum. This is adequate for present
      needs. 11 donors have been found positive for human immunodeficiency virus (HIV)
      since testing started in 1987, 8 of these in the last year and a half. No case of
      transmission of HIV by transfusion in Papua New Guinea has been established.
      Although the prevalence varies in different areas, on average 15% of donors are
      positive for hepatitis B. The impact of these figures, future requirements for
      quantity of blood and the need for additional testing of donations for hepatitis
      C (HCV) and cytomegalovirus (CMV) will require clear evaluation of the choices
      and firm decisions.

PMID- 9522850
TI  - Intestinal infarction in systemic lupus erythematosus--report of a case with an
      unusual obliterative vascular lesion.
AB  - Intestinal infarction is a rare complication of systemic lupus erythematosus
      (SLE). A 26-year-old Papua New Guinean female who developed such a complication
      and underwent emergency laparotomy is described. The pathological changes in the
      mesenteric vessels and possible pathogenetic mechanisms are discussed. The
      relevant literature is briefly reviewed.

PMID- 9522851
TI  - Sclerosing stromal tumour of the ovary.
AB  - Two cases of sclerosing stromal tumour of the ovary in young Melanesian females
      are described and the differential diagnosis is discussed. Sclerosing stromal
      tumour of the ovary is a rare benign tumour of ovarian stromal origin which is
      associated with endocrine activity in a few cases. One of the patients presented
      with signs of precocious puberty and the tumour in this patient was considered as
      a functioning lesion.

PMID- 9522852
TI  - Basics of molecular biology and its applications: I. Molecular biology in
      medicine: basic concepts.
AB  - Medicine has, in recent years, incorporated wave after wave of new scientific
      discoveries and technologies. Molecular medicine is one of these technologies and
      shows a dramatic example of the impact of advances in basic science. Advances in
      molecular biology have revolutionized daily clinical practice, particularly in
      developed countries, such that practitioners who received their medical education
      decades ago now need to adapt to this new discipline. While molecular medicine
      may not be a priority health issue in developing countries such as Papua New
      Guinea, it is equally important to ensure that the basic principles of knowledge
      and understanding of what goes on in that field form part of today's teaching of
      all practitioners of medicine and allied health workers. The three papers in this
      series aim to present molecular biology and its medical applications in as simple
      and lucid a manner as possible so that its scientific basis and principles as
      well as its potential for diagnosis and management of diseases are well
      appreciated.

PMID- 9522853
TI  - The management of cryptococcal meningitis in Papua New Guinea.
AB  - Cryptococcal meningitis is a difficult disease to treat and requires biochemical
      and haematological monitoring to detect the common adverse effects of treatment.
      Combination therapy with amphotericin B and flucytosine for at least 6 weeks is
      the best treatment so far evaluated. The role of azole drugs should become
      clearer as the results of large multicentre studies become available in the
      future. High case fatality and morbidity rates despite standard treatment suggest
      that other ancillary treatments such as corticosteroids and other treatments
      directed at lowering raised intracranial pressure may also be required in some
      patients.

PMID- 9522854
TI  - Childhood disabilities in Papua New Guinea.

PMID- 9522855
TI  - Prevalence of vaginal infections with bacterial vaginosis, Trichomonas vaginalis
      and Candida albicans among pregnant women at the Port Moresby General Hospital
      Antenatal Clinic.
AB  - A clinico-sociodemographic and microbiological survey was carried out at the Port
      Moresby General Hospital Antenatal Clinic to determine the prevalences of
      bacterial vaginosis, Trichomonas vaginalis and Candida albicans vaginal
      infections in pregnancy and to examine if the infections had any association with
      some suspected sociodemographic risk factors. The study was carried out between
      December 1990 and January 1991. Of 206 consecutive subjects surveyed, 79 (38%)
      had symptomatic infection. However, on speculum examination, abnormal discharge
      was seen in 188 (91%). 118 (57%) had microbiologically confirmed infection. The
      prevalences of the individual infections were T. vaginalis 19%, C. albicans 23%
      and bacterial vaginosis 23%. Combined infection, i.e. two infections occurring
      together in the same subject, was uncommon. None of the infections had an
      association with any of the sociodemographic characteristics studied. Of the 118
      positive subjects, 52 (44%) complained of vaginal discharge and 55 (47%)
      complained of pruritus.

PMID- 9522856
TI  - Symphysiotomy or caesarean section after failed trial of assisted delivery.
AB  - The perinatal and maternal outcomes of 65 symphysiotomies and 108 caesarean
      sections carried out after failed trial of assisted delivery at the Port Moresby
      General Hospital between 1988 and 1994 were retrospectively analyzed. There were
      no significant differences in perinatal outcomes between the treatment groups.
      There were no maternal deaths in either group. Mothers who had symphysiotomy had
      a longer postoperative stay in hospital but fewer complications requiring further
      surgery. There are many advantages of symphysiotomy, particularly in developing
      countries, following a failed trial of assisted delivery, provided the
      indications for it are strictly met. Obstetricians experienced in the technique
      are able to apply it at the optimal time, with long-term benefit to their
      patients, who thereby avoid the risks of pregnancy subsequent to caesarean
      section.

PMID- 9522857
TI  - Knowledge about AIDS and follow-up compliance in patients attending a sexually
      transmitted disease clinic in the highlands of Papua New Guinea.
AB  - In a survey of 300 consecutive new attenders at the Porgera Health Centre
      Sexually Transmitted Disease Clinic information was obtained regarding knowledge
      about AIDS from male and female attenders. The differences between the sexes
      regarding a variety of socioeconomic variables, knowledge about AIDS and their
      compliance to follow-up appointments were studied as well as possible
      relationships between these social variables and the degrees of AIDS knowledge
      and compliance. Males tended to originate from further afield, be more educated,
      be either in salaried employment or not working at all, and be single as compared
      to females. They also admitted to more extramarital sexual contacts and received
      more adequate treatment. Knowledge about AIDS was also significantly higher
      amongst male attenders and in this group was correlated strongly with overall
      educational attainment and employment status but did not show any relationship
      with the number of extramarital contacts admitted to. Only 9% of the patients
      knew about condoms and their role in prevention. Follow-up compliance was
      generally poor, and not significantly higher in those with higher scores of
      knowledge about AIDS, but showed a relationship with the type of disease being
      treated and with the ultimate adequacy of treatment received.

PMID- 9522858
TI  - Audit of death certificates.
AB  - Information on the number and causes of death is one of the basic components of a
      country's health information system. Data are usually derived from death
      certificates and health facility discharge summaries. There are usually several
      causes of error in the routine collection of this information. A criteria audit
      of death certificates is presented to assess these sources of error in Papua New
      Guinea. This procedure involved the systematic and critical analysis of hospital
      mortality as reported in death certificates. The audit is simple, cheap and
      useful for monitoring the quality of the mortality information which will be used
      in health planning and management. Quality criteria are defined and the
      completeness and relevance of the data audited are discussed. Recommendations for
      the improvement of the health information system are made.

PMID- 9522859
TI  - The clinical competency of community health workers in the eastern highlands
      province of Papua New Guinea.
AB  - A case study of the clinical competency of community health workers employed in
      the Eastern Highlands Province of Papua New Guinea was conducted in March 1993.
      Of the 79 who graduated from the Onamuga Community Health Worker Training School
      between 1989 and 1992, only 24 were currently employed in the province. Current
      knowledge and clinical competency were compared with results on completion of
      basic community health worker training. Results showed that 22 of the 24
      maintained their knowledge competency, and 15 maintained clinical competency. It
      was found that those community health workers (CHWs) employed at a health
      subcentre use 40% to 50% of their skills, whilst those at a district health
      centre or provincial hospital use only 20% to 30% of their skills. Only 8% of the
      CHWs studied used all the skills obtained in their basic training. This study
      indicates that the CHW is being viewed by some health managers as a replacement
      for the nurse aide. If CHWs' skills are to be maintained, certainly good
      supervision, inservice training and adequate logistic support are needed, but so
      also is a change in management thinking. The CHW has been trained specifically to
      improve the access to essential primary health care services of people living in
      rural areas, especially in preventive and maternal and child health care. If in
      practice the CHW is not given the opportunity to practise and hence maintain
      these skills, the whole logic of the CHW training scheme will need to be
      reexamined.

PMID- 9522863
TI  - Pneumoperitoneum in a five-day-old baby: a case report.
AB  - A five-day-old male was admitted to Mt Hagen Hospital with a history of vomiting,
      fever and rapidly progressive abdominal distension of one-day duration. Urgent
      abdominal X-ray revealed pneumoperitoneum. Laparotomy revealed a malrotation of
      the intestine with jejunal perforation. The baby died postoperatively, 21 hours
      after admission. The importance of plain abdominal X-rays and reliance on
      'classical' plain film radiographic signs is highlighted.

PMID- 9522861
TI  - Relative repellency of woodsmoke and topical applications of plant products
      against mosquitoes.
AB  - The repellent action of various plant products was evaluated against anopheline
      and culicine mosquitoes in a rural village in the Wosera area, Papua New Guinea.
      A 5 x 5 Latin square design was used. Wood from four home-grown plant species was
      burned outdoors in the first experiment, and mosquitoes attracted to human bait
      were collected from 1800 to 2400 hours. In the second experiment, bruised leaves
      from another four plant species were rubbed on to the legs of human baits
      followed by mosquito collections. Woodsmoke and topical applications reduced
      biting of human volunteers by 79% and 51%, respectively. This low-technology
      control method may be included in the range of options for householders in order
      to reduce mosquito nuisance and improve their standard of health.

PMID- 9522860
TI  - Rehabilitation of the handicapped child--what about the caregiver?
AB  - The mental health of caregivers of handicapped children (n = 68) and of
      caregivers of children with minor ailments (n = 40) was assessed using the
      General Health Questionnaire (GHQ). In the comparative study, the caregivers of
      handicapped children had a significantly higher mean score (6.8), which was above
      the threshold score of 4. This suggests that the task of caring for disabled
      children may have a stressful impact on the caregivers which may contribute to
      psychiatric morbidity. There is a need periodically to assess the mental health
      of the caregiver, even as the rehabilitation of the handicapped child progresses.
      Addressing the psychological disturbances in the caregiver should form part of
      the treatment of the handicapped child.

PMID- 9522862
TI  - Ten cases of bush thoracotomy in Enga Province, Papua New Guinea.
AB  - Bush thoracotomy is the traditional practice of incising the chest wall into the
      pleural space in an attempt to relieve chest pain. The procedure is practised by
      village people in Enga Province in the highlands of Papua New Guinea and causes
      considerable morbidity. The beliefs on which it is based are discussed, and the
      methods employed described. Ten cases presenting after bush thoracotomy are
      documented, and one case of bush laparotomy noted. A way of reducing the
      morbidity from this practice is suggested.

PMID- 9522864
TI  - Symphysiotomy: technique, problems and pitfalls, and how to avoid them.

PMID- 9522865
TI  - Social and ecological considerations in the prevention of enteric infections.

PMID- 9522867
TI  - Persistent diarrhoea in children admitted to Port Moresby General Hospital.
AB  - A retrospective study of the records of children admitted to Port Moresby General
      Hospital with diarrhoea during 1992 and 1993 was carried out to determine the
      morbidity, mortality and risk factors associated with persistent diarrhoea. 858
      admissions of children under five years of age who had diarrhoea were identified
      from the ward admission registers, and case records for 724 were studied.
      Persistent diarrhoea occurred in 20%, and nearly half of these were in the 12-23
      months age group. Children with persistent diarrhoea had a case fatality rate of
      4.9%. Seasonality was similar for both persistent and non-persistent diarrhoea.
      In the crude analysis children of 12 months and older had a greater risk of
      developing persistent diarrhoea than those less than 12 months (odds ratio for
      children 12-23 months was 2.0 and for children 24-59 months 1.7; confidence
      intervals were 1.2-3.1 and 1.0-2.9 respectively); however, this difference was
      not found after logistic regression analysis. Poor nutritional status was a
      significant risk factor for persistent diarrhoea and remained so after
      controlling for confounding variables (odds ratio 2.7; confidence interval 1.8
      4.0).

PMID- 9522866
TI  - Diarrhoea in children in Papua New Guinea.
AB  - National data for diarrhoeal disease in children can only be used as a very rough
      guide to morbidity and mortality, since they are based on incomplete reporting.
      Furthermore, when only one diagnosis per attendance, admission or cause of death
      is recorded, the true importance of diarrhoea as a cause of morbidity and
      mortality may be obscured. This may in part explain discrepancies between figures
      recorded in national and hospital statistics and those recorded in detailed
      studies of diarrhoeal admissions. While there appear to be quite marked
      differences in the relative importance of diarrhoea in different parts of the
      country, and while diarrhoeal disease is less of a scourge than in some other
      parts of the world, it is nevertheless a major cause of attendance at health
      facilities, the second or third most common cause of admission to many of the
      hospitals in the country, and a significant and often preventable cause of death.
      Limited studies of diarrhoeal aetiology indicate the major importance of
      rotavirus, Shigella and enteropathogenic and enterotoxigenic Escherichia coli.
      The control of diarrhoeal diseases in children is based not only on early and
      appropriate treatment, but also on preventive strategies. These include
      breastfeeding (which has saved the lives of many thousands of Papua New Guinean
      children and which is once again under threat), ensuring good host defence by
      good nutrition, immunization and early treatment of childhood illness, and
      ensuring satisfactory sanitation and hygiene. Increasing fluid intake to prevent
      dehydration remains the most important part of the early management of acute
      diarrhoeal disease. In the management of children with dehydration, UNICEF
      glucose-based oral rehydration therapy is widely available but not used as well
      as it should be. There are significant advantages in cereal-based oral
      rehydration solutions, and the use of such solutions, locally prepared, should be
      encouraged. Breastfeeding should be continued during episodes of diarrhoea,
      unless there is the specific contraindication of lactose intolerance. In all
      events the child's nutritional intake should be maintained and if possible
      increased during episodes of diarrhoea. There are specific indications for the
      use of antibiotics in the management of children with diarrhoea. They should not
      be used, and may be harmful, in the absence of these indications. Persistent
      diarrhoea--lasting more than 14 days--is associated with a high mortality and
      severe malnutrition. It is therefore important that children whose diarrhoea is
      prolonged for more than 7 days are managed appropriately, using the standard
      guidelines.

PMID- 9522868
TI  - Acceptability of a rice-based oral rehydration solution in Port Moresby General
      Hospital's Children's Outpatient Department.
AB  - The guardians of children brought to the Port Moresby General Hospital's
      Children's Outpatient Department with a chief complaint of diarrhoeal disease
      were questioned regarding their preference of glucose-based vs rice-based oral
      rehydration solution (ORS) in order to determine the acceptability of a rice
      based ORS. Of the 93 guardians interviewed, greater than 60% preferred the
      glucose-based solution in its mixability, appearance and taste, and 65% initially
      reported that their children preferred the taste of the glucose solution.
      However, after a 30-minute trial, only 58% of children still preferred the
      glucose solution. In a country where diarrhoeal disease is a leading cause of
      child death and guardians are the primary health care providers, the
      acceptability of an ORS is critical to the morbidity and mortality of Papua New
      Guinea's children.

PMID- 9522869
TI  - A 3-hour quantitative comparison of glucose-based versus rice-based oral
      rehydration solution intake by children with diarrhoea in Port Moresby General
      Hospital.
AB  - Measurements were made of the intake of a WHO/UNICEF glucose-based and a rice
      cereal-based oral rehydration solution (ORS) by children with diarrhoea. Twenty
      children who presented to the Children's Outpatient Department at Port Moresby
      General Hospital with acute diarrhoea and mild dehydration were randomly assigned
      to an ORS and measurements were taken over the following 3 hours. For data
      analysis, the patients were paired by weight. Testing the means of the paired
      samples by t test showed that there was no significant difference between the
      amount of rice ORS and the amount of glucose ORS taken over 3 hours.

PMID- 9522870
TI  - Improved diagnosis as an aid to better surveillance of Taenia solium
      cysticercosis, a potential public health threat to Papua New Guinea.
AB  - Taenia solium cysticercosis has been recognized as a public health problem in
      Indonesian Irian Jaya since its unfortunate introduction in a number of infected
      pigs imported from Bali. From its original point of introduction in 1971, the
      infection has spread from the Wissel Lakes area to other places within Irian
      Jaya. The present situation at the border between Irian Jaya and Papua New Guinea
      (PNG) is difficult to assess accurately but, in light of the flow of refugees and
      the traditional rights of movement of people with their pigs in the border area,
      PNG populations are now at risk. Government health officers and veterinarians in
      PNG are well aware of this threat and have been watching closely for transmission
      of Taenia solium into PNG. A rigorous survey of Irianese refugees at the border
      and surrounding areas in PNG using recently developed immunodiagnostic procedures
      such as the EITB (enzyme immunoelectrotransfer blot) for detecting human and pig
      cysticercosis and the dipstick ELISA (enzyme-linked immunosorbent assay) for
      identifying T. solium carriers, coupled with careful assessment of medical
      history and clinical and stool examination, is, however, required. Such a study
      would allow evaluation of the prevalence of cysticercosis and taeniasis in Irian
      Jayan refugees residing in camps in PNG. The study would also determine the
      extent to which the parasite has spread easterly and, importantly, whether
      cysticercosis/taeniasis has crossed the border and is endemic in PNG, thereby
      constituting a potentially serious public health problem.

PMID- 9522871
TI  - Gastrointestinal nematodes: the Karkar experience.
AB  - This paper reviews our research on the hookworm Necator americanus over several
      years. Our field site for the research was on Karkar Island, Papua New Guinea,
      where we found a prevalence of N. americanus infection among adults of nearly
      100%. The intensity of infection was related to host age and to the development
      of iron deficiency anaemia, which occurred at a much lower infection intensity
      than had been previously reported. We studied the immune response to infection
      and our results initially suggested that antibody responses and eosinophilia do
      not protect the host against infection. However, we have more recently found a
      negative correlation of both IgE and eosinophilia with the weight and fecundity
      of N. americanus which suggests that the immune response does have some effect on
      N. americanus and that this immunity is dependent on the Th2 subset of T
      lymphocytes. Following treatment for hookworm, the prevalence of N. americanus
      returned almost to pretreatment levels within 2 years, with the rate of
      acquisition of adult worms independent of host age. A significant predisposition
      to hookworm infection was demonstrated by individuals. Prevention will result
      from measures to reduce the transmission and intensity of infection, and can be
      achieved through improved sanitation or by vaccination. However, vaccination is
      not yet a viable option because of our limited knowledge about protective
      immunity.

PMID- 9522872
TI  - The new problem of typhoid fever in Papua New Guinea: how do we deal with it?
AB  - This paper reviews some of the issues relating to typhoid fever in Papua New
      Guinea. Before the mid-1980s only sporadic cases of typhoid were reported but it
      is now one of the greatest public health problems in the highlands and some urban
      areas. In one study near Goroka an annual incidence rate of 1208 per 100,000
      people was found, with settlers from other areas at greater risk than the local
      landowners. Problems relating to management included differentiation from other
      diseases, the limitations of the Widal test and poor compliance among
      outpatients. In Papua New Guinea it appears that transmission is largely from
      person to person, with little evidence for water-borne transmission. The
      prolonged convalescent excretion of Salmonella typhi and the difficulties this
      poses for control of the disease are discussed. Prevention will only be achieved
      in the long term by improvements in hygiene and sanitation, though more immediate
      control could be achieved by vaccination with an appropriate vaccine.

PMID- 9522873
TI  - Typhoid in the highlands of Papua New Guinea 1984-1990: a hospital-based
      perspective.
AB  - A first-hand account is given of the epidemic of typhoid in the Goroka area as it
      evolved from 1984 to 1990. The monthly admissions for typhoid to Goroka Base
      Hospital showed a peak in 1988. The sex and age distribution showed a
      predominance of young adults. The overall case fatality rate of hospitalized
      patients was of the order of 10-15%; in a carefully documented group of 374
      patients 27% were assessed as having severe typhoid and this subgroup had a case
      fatality rate of 44%. The clinical features were studied in 516 patients. The
      high mortality appeared to result from septic shock; ileal perforation was found
      in only 1.3% of patients. A skin lesion equivalent to but significantly different
      from the classic rose spot was found in 30% of patients. The typhoid facies was
      commonly encountered in patients with well-established typhoid. Cerebellar tremor
      and hearing loss were frequent diagnostic findings. Blood and bone marrow
      cultures were used to confirm the diagnosis; bone marrow culture proved
      practicable but gave little increased yield over blood culture. A clinical
      algorithm to help distinguish typhoid and malaria was developed, principally for
      use in health centres in the highlands. The mainstay of treatment was
      chloramphenicol and very few problems were encountered with its use in
      inpatients. Bacteriological resistance to chloramphenicol did not develop over
      the study period. Other drugs, such as fluorinated quinolones, may be more
      effective when all aspects are considered, despite higher cost, but this remains
      to be investigated. Hydrocortisone in patients with severe disease was evaluated
      and shown to be ineffective but whether high-dose dexamethasone would reduce the
      mortality from typhoid in patients in Papua New Guinea still remains an
      unanswered question.

PMID- 9522874
TI  - The role of the laboratory in the diagnosis and management of typhoid fever.
AB  - In typhoid-endemic areas the results obtained from the laboratory are important
      in confirming the clinical diagnosis of typhoid and may also contribute to
      decisions made on the management and treatment of typhoid cases. Isolation of
      Salmonella typhi remains the gold standard, with culture from bone marrow
      aspirate or a combination of specimens from other body sites resulting in the
      greatest sensitivity. Antibody detection techniques may still provide valuable
      information, but only if the results are interpreted in the context of the
      background antibody levels in the local population. None of the available antigen
      detection techniques have been consistently demonstrated to be of diagnostic
      value and a recently developed polymerase chain reaction (PCR) for the detection
      of Salmonella typhi has yet to undergo a full-scale clinical evaluation. The
      initial identification of chronic typhoid carriers relies upon the detection of
      elevated Vi capsular antibody levels, but seeking out chronic carriers will be of
      limited value in controlling the spread of typhoid in areas where transmission is
      principally mediated by convalescent excretors. Whilst resistance of Salmonella
      typhi to antibiotics has emerged as an increasing problem in some areas of the
      world, it is still uncommon in isolates from Papua New Guinea. However,
      monitoring of antibiotic susceptibility patterns will ensure that signs of
      developing resistance are detected early and that the appropriate action is
      taken.

PMID- 9522875
TI  - Changing hygiene behaviour in Papua New Guinea.
AB  - Sanitation and water supplies are critical to health and an adequate standard of
      living. In Papua New Guinea water supplies in both rural and urban areas are
      installed with no attention to the social and cultural aspects of water use and
      personal hygiene. This paper argues that improved hygiene and sanitation could be
      achieved if sufficient resources were focused on the people who use water and
      sanitation systems and not simply on the systems themselves.

PMID- 9522876
TI  - A review of the current status of enteric vaccines.
AB  - Much progress has been made in developing vaccines against the most important
      enteric infections. Two new vaccines against typhoid fever (oral Ty21a and
      parenteral Vi polysaccharide) have been licensed in many countries. Newer, more
      sophisticated typhoid vaccines undergoing clinical testing include recombinant
      attenuated Salmonella typhi strains and Vi polysaccharide-carrier-protein
      conjugate vaccines. Two inactivated oral cholera vaccines, consisting of
      inactivated Vibrio cholerae O1 bacteria alone or in combination with B subunit of
      cholera toxin, each conferred 50-53% protection over three years in a field trial
      in Bangladesh where subjects were immunized with a three-dose regimen. An
      engineered live oral cholera vaccine, strain CVD 103-HgR, has been shown in
      extensive clinical trials to be well tolerated by children and adults in less
      developed countries and highly immunogenic following administration of just a
      single oral dose; a large-scale field trial of the efficacy of this vaccine is
      underway. In experimental challenge studies in volunteers, a single dose of CVD
      103-HgR confers significant protection against challenge with wild-type V.
      cholerae O1 of either classical or El Tor biotype and either Inaba or Ogawa
      serotype. Several candidate vaccines against Shigella and enterotoxigenic
      Escherichia coli are in clinical trials. A multivalent rotavirus vaccine (rhesus
      reassortant vaccine) is undergoing extensive field testing in developed and less
      developed countries.

PMID- 9522877
TI  - When does the patient with diarrhoea need surgery?

PMID- 9522878
TI  - 1997 Memory Disorders Conference. Proceedings and abstracts.

PMID- 9522879
TI  - Individual error in radiology.

PMID- 9522880
TI  - Rates of disagreement in imaging interpretation in a group of community
      hospitals.
AB  - RATIONALE AND OBJECTIVES: Prospective studies of radiologists' interpretations of
      selected radiographs reported 20-40 years ago indicated error rates of 30% and
      higher. The authors retrospectively evaluated the interpretations of groups of
      radiologists and determined a range of rates of disagreement in interpretation.
      Quality assessment or recredentialing may add to the importance of such studies
      in the future. MATERIALS AND METHODS: Over a 7-year period, a team of
      radiologists reviewed imaging interpretations in the radiology departments of six
      community hospitals. Each review, which lasted about 3 days, included evaluation
      of the interpretations of a 3%-4% sample of the images read by the radiologists
      at these hospitals. Reading errors were quantitated and evaluated qualitatively.
      RESULTS: In a review of over 11,000 images read by 35 radiologists, the authors
      found a 4.4% mean rate of interpretation disagreement; only one radiologist had a
      mean rate above 8%. Qualitative analysis of the interpretation errors revealed a
      mean rate of 3.0% of errors that were considered to be below an acceptable
      standard of care. Radiologists whose errors included a relatively high proportion
      of false-positive findings tended to make relatively fewer total errors.
      CONCLUSION: Rates of disagreement for a broad range of studies that radiologists
      interpret in a community hospital setting appear to be far lower than earlier
      studies on selective radiographs indicated.

PMID- 9522881
TI  - Automated computerized classification of malignant and benign masses on digitized
      mammograms.
AB  - RATIONALE AND OBJECTIVES: To develop a method for differentiating malignant from
      benign masses in which a computer automatically extracts lesion features and
      merges them into an estimated likelihood of malignancy. MATERIALS AND METHODS:
      Ninety-five mammograms depicting masses in 65 patients were digitized. Various
      features related to the margin and density of each mass were extracted
      automatically from the neighborhoods of the computer-identified mass regions.
      Selected features were merged into an estimated likelihood of malignancy by,
      using three different automated classifiers. The performance of the three
      classifiers in distinguishing between benign and malignant masses was evaluated
      by receiver operating characteristic analysis and compared with the performance
      of an experienced mammographer and that of five less experienced mammographers.
      RESULTS: Our computer classification scheme yielded an area under the receiver
      operating characteristic curve (Az) value of 0.94, which was similar to that for
      an experienced mammographer (Az = 0.91) and was statistically significantly
      higher than the average performance of the radiologists with less mammographic
      experience (Az = 0.81) (P = .013). With the database used, the computer scheme
      achieved, at 100% sensitivity, a positive predictive value of 83%, which was 12%
      higher than that for the performance of the experienced mammographer and 21%
      higher than that for the average performance of the less experienced
      mammographers (P < .0001). CONCLUSION: Automated computerized classification
      schemes may be useful in helping radiologists distinguish between benign and
      malignant masses and thus reducing the number of unnecessary biopsies.

PMID- 9522882
TI  - Value of case-of-the-week presentations on the radiology component of the
      Comprehensive Clinical Assessment examination.
AB  - RATIONALE AND OBJECTIVES: The Comprehensive Clinical Assessment (CCA) examination
      at the University of Michigan Medical School is a series of test stations through
      which the mastery of clinical skills is evaluated. The purpose of this study was
      to determine whether student performance on the radiology station improved in
      years when radiology faculty presented case-of-the-week unknowns to the 3rd-year
      students. MATERIALS AND METHODS: The authors compared four separate classes of
      medical students in examination years 1993, 1994, 1995, and 1996 by using the
      total CCA examination score, the radiology station score, and radiology station
      pass/fail rates. Radiology case-of-the-week presentations were given by the
      radiology faculty only in academic years 1993-1994 and 1994-1995 (examination
      years 1994 and 1995). RESULTS: The means and standard deviations of the radiology
      station scores for the examination years when case-of-the-week presentations were
      not given, 1993 and 1996, were 78.92 +/- 13.62 and 79.76 +/- 13.62, respectively.
      In the years case-of-the-week presentations were given, 1994 and 1995, the
      radiology station scores averaged 90.83 +/- 8.58 and 89.97 +/- 9.66, respectively
      (P < .001, global alpha = .05). Total CCA percentage correct scores were similar
      for all years studied. In 1993 and 1996, 7.6% and 5.3% of students, respectively,
      failed the radiology station. In 1994 and 1995, 0.4% and 0% of students,
      respectively, failed (P < .0001). CONCLUSION: Case-of-the-week presentations by
      radiology faculty increased 3rd-year students' basic radiologic knowledge as
      evidenced by increased scores on the radiology station of the CCA examination.

PMID- 9522883
TI  - Computed radiography versus screen-film mammography in detection of simulated
      microcalcifications: a receiver operating characteristic study based on phantom
      images.
AB  - RATIONALE AND OBJECTIVES: The authors compare a 43-micron computed radiographic
      system with a mammographic screen-film system for detection of simulated
      microcalcifications in an observer-performance study. MATERIALS AND METHODS: The
      task of detecting microcalcifications was simulated by imaging aluminum wire
      segments (200-500 microns in length; 100, 125, or 150 microns in diameter) that
      overlapped with tissue background structures produced by beef brisket. A total of
      288 such simulations were generated and examined with both computed radiography
      and conventional screen-film mammography techniques. Computed radiography was
      performed with high-resolution plates, a 43-micron image reader, and a 43-micron
      laser film printer. Computed radiographic images were printed with simple
      contrast enhancement and compared with screen-film images in a receiver operating
      characteristic study in which experienced readers detected and scored the
      simulated microcalcifications. Observer performance was quantitated and compared
      by computing the area under the receiver operating characteristic curve. RESULTS:
      Although the resolution of the computed radiography system was better than that
      of commercial systems, it fell short of that of screen-film systems. For the 100
      micron microcalcifications, the difference in the average area under the curve
      was not statistically significant, but it was significant for the larger
      simulated microcalcifications: the average area under the curve was 0.58 for
      computed radiography versus 0.76 for screen-film imaging for the 125-micron
      microcalcifications and 0.83 versus 1.00, respectively, for the 150-micron
      microcalcifications. CONCLUSION: Observer performance in the detection of small
      simulated microcalcifications (100-150 microns in diameter) is better with screen
      film images than with high-resolution computed radiographic images.

PMID- 9522884
TI  - Incorporation of a set enumeration trees-based classifier into a hybrid computer
      assisted diagnosis scheme for mass detection.
AB  - RATIONALE AND OBJECTIVES: The authors evaluated whether a hybrid classifier of
      two independent computer-aided diagnosis (CAD) schemes, the set enumeration (SE)
      trees approach and an artificial neural network (ANN), could improve the
      detection of masses on digitized mammograms. The potential benefits resulting
      from the interpretability of the SE trees model was also explored. MATERIALS AND
      METHODS: Two hundred thirty verified mass regions and 230 negative but suspicious
      regions were randomly selected from 618 digitized mammograms. Each region was
      represented by a 24-parameter feature vector. These features were used as input
      data for the SE trees and ANN-based schemes. After the positive and negative
      regions were randomly segmented into five exclusive partitions, a fivefold cross
      validation method was applied to evaluate and compare the performance of the SE
      trees, ANN, and hybrid system in the identification of masses. RESULTS: The
      performance of the SE trees approach was comparable to that of the ANN. The
      average area under the receiver operating characteristic (ROC) curves for all
      five partitions was 0.88 (standard deviation, 0.04). Owing to the relatively low
      correlation between the region-based results of the SE trees and ANN methods, the
      hybrid classifier yielded a significantly improved performance, with an area
      under the ROC curve of 0.94 (standard deviation, 0.02; P < .05). CONCLUSION: The
      hybrid CAD scheme significantly improved performance. The amenability of the SE
      trees models to interpretation may aid in the assessment of the importance of
      specific features.

PMID- 9522885
TI  - A multipurpose model of radiology appropriateness criteria.
AB  - RATIONALE AND OBJECTIVES: Appropriateness criteria and practice guidelines are
      being developed in attempts to improve the cost-effectiveness of medical care.
      The authors sought to make a set of radiology appropriateness criteria usable for
      education, computer-based decision support, and utilization review. MODEL
      DEVELOPMENT: Sixty clinical conditions from the American College of Radiology's
      appropriateness criteria were selected. To make the information more suitable for
      automation, the names of the imaging procedures were standardized. Indexing terms
      were assigned to identify clinical conditions and to distinguish between each
      condition's variants. Semantic relationships between terms were defined.
      Information about the clinical conditions and variants, radiologic procedures,
      indexing terms, and relationships was encoded into a standardized language for
      document interchange. IMPLEMENTATION: The 1,956 rows in the appropriateness
      criteria tables for the 60 clinical conditions and their 212 variants were mapped
      into references to 163 distinct imaging procedures. The system's knowledge base
      included 301 indexing terms and 569 additional terms. CONCLUSION: Radiology
      appropriateness criteria can be indexed and encoded into a form that facilitates
      their use and interchange. The use of open, internationally accepted standards is
      an important step to make such knowledge portable and suitable for integration
      with evolving computer-based patient record systems.

PMID- 9522887
TI  - Disabled residency candidates and federal law: implications of the Americans with
      Disabilities Act.

PMID- 9522886
TI  - Nonadhesive liquid embolic agent: role of its components in histologic changes in
      embolized arteries.
AB  - RATIONALE AND OBJECTIVES: The authors evaluated the safety and efficacy of a
      nonadhesive liquid embolic material and the role of its components in histologic
      changes in embolized arteries. MATERIALS AND METHODS: A Eudragit-E mixture (Rohm
      Chemische Fabrik, Darmstadt, Germany) was made of a cationic copolymer (Eudragit
      E) dissolved in an equal volume of absolute ethanol and iopamidol. The Eudragit-E
      mixture, an ethanol-iopamidol mixture, and an iopamidol-saline mixture were
      injected into 12 rabbit renal arteries each. Three rabbits from each group were
      followed up for 1 day, 1 week, 1 month, and 3 months, at which time they were
      sacrificed. Kidneys were removed for histologic examination. RESULTS: The
      Eudragit-E mixture occluded all renal arteries without difficulty: the arteries
      did not recanalize. Histologically, acute vasculitis was caused by both the
      Eudragit-E and ethanol-iopamidol mixtures, but not by the iopamidol-saline
      mixture. Small infarctions were elicited with the ethanol-iopamidol mixture but
      not with the iopamidol-saline mixture. CONCLUSION: The Eudragit-E mixture is
      effective and easy to handle. Fifty percent ethanol may play a role in vessel
      occlusion with Eudragit-E mixture and in acute vasculitis.

PMID- 9522888
TI  - News from the Academy of Radiology Research: why we need a National Institute of
      Biomedical Imaging.

PMID- 9522889
TI  - CT and MR imaging of nonaccidental pediatric head trauma.

PMID- 9522890
TI  - Results of the 1997 survey of the American Association of Academic Chief
      Residents in Radiology.
AB  - RATIONALE AND OBJECTIVES: The American Association of Academic Chief Residents in
      Radiology annually surveys residency programs on a variety of issues related to
      residency training. The survey results allow individual programs to compare
      features of their programs with national averages and to gauge trends in
      radiology residency training. MATERIALS AND METHODS: Questionnaires were mailed
      to the chief residents in 180 accredited radiology residency programs in the
      United States. A variety of demographic and common-interest questions were asked.
      The 1997 survey focused on American Board of Radiology (ABR) examination
      preparation, residency curriculum, and socioeconomic issues relevant to
      graduating radiology residents. RESULTS: Completed surveys from 73 programs (41%)
      were returned. Areas of curriculum concern among chief residents reflected
      primarily current turf issues. A higher than expected percentage of residents
      considered their training to be inadequate in nonneurologic magnetic resonance
      imaging and chest, musculoskeletal, and genitourinary radiology. Job security is
      a major emerging concern for radiology residents who are considering careers in
      private practice. The practice of remembering and transcribing questions from the
      ABR written examination is common, and these questions are a valued resource in
      preparing for the diagnostic section of the written examination. Most residents
      attend a commercial review course before the oral examination, and the majority
      of programs also provide internal review courses. CONCLUSION: A higher than
      expected percentage of chief residents expressed concern regarding training in
      subspecialties of radiology that are neither areas of turf dispute nor areas
      where certificate of additional qualification examinations are offered. Radiology
      programs and residents expend substantial resources on preparation for the ABR
      examinations in addition to the usual 4-year curriculum. The most valued resource
      for the diagnostic section of the examination is almost certainly not equally
      available. Radiology residents are increasingly concerned about future job
      security.

PMID- 9522891
TI  - Hyaluronan in human deciduous tooth germs in the bell stage. Histochemistry and
      immunohistochemistry.
AB  - The primary aim of the present study was a localization of hyaluronan (HA) in
      human deciduous tooth germs in the bell stage. HA was compared to the content of
      chondroitin sulfates (CSs). HA was detected with a biotin-labeled HA-binding
      protein (HABP) and CS with a monoclonal antibody. As controls, enzyme digestions
      were carried out. Furthermore, the glycosaminoglycans were investigated
      histochemically with enzyme digestions followed by alcian blue staining. The
      investigation showed a considerable content of HA in the stellate reticulum,
      although CS was also found, primarily when treatment with protease was omitted.
      The dental papilla contained both HA and CS, while the predentin and the dentin
      contained only CS. The enamel did not contain any CS, but some staining with HABP
      was observed along the borderline between the ameloblasts and the enamel. The
      significance of HA in the stellate reticulum is discussed. The importance of
      carrying out investigations with and without protease digestions is stressed.

PMID- 9522892
TI  - A fifth pharyngeal arch artery does not exist in rat.
AB  - The development of the caudal pharyngeal arch arteries was studied in perfused
      rat embryos in the interval of embryonic day 12 1/2 to embryonic day 13 3/4 using
      semithin serial sections and computer-aided 3-dimensional reconstructions. The
      fourth pharyngeal arch artery was already developed at embryonic day 12 1/2. The
      sixth developed from cystic enlarged vascular sprouts at embryonic day 13 1/4. A
      real fifth pharyngeal arch artery was not found between the fourth and sixth
      artery. Instead a vascular plexus was present at embryonic day 12 1/2 which was
      interposed between the epithelial sheets of the fourth pharyngeal pouch and the
      lower cervical sinus. At the onset of development this plexus arose ventrally and
      dorsally from the fourth pharyngeal arch artery only. Subsequent to the
      development of the sixth pharyngeal arch artery, vascular branches arose
      ventrally and dorsally from this artery, too. The plexus underwent incipient
      involution from embryonic day 13 1/4. It arose either from the fourth or the
      sixth pharyngeal arch artery only from embryonic day 13 3/4. It drained to the
      venous system. Branches of the plexus which ran towards the epithelial sheet of
      the lower cervical sinus became prominent.

PMID- 9522893
TI  - Development of lung, kidney and skin in the brushtail possum, Trichosurus
      vulpecula.
AB  - The thyroid gland is not present at birth in marsupials and thyroid function
      begins during the latter half of pouch life. The hormonal output of the thyroid
      gland is important for normal development. In this study the structure of the
      lung, kidney and skin of the developing possum was examined and the structural
      development of these three organs was described. The lung of the newborn
      brushtail possum was functional and continued to develop during pouch life,
      alveolar formation beginning at day 39 and concluding at day 113 postpartum. The
      mesonephric kidneys of the newborn possum degenerated and were replaced by the
      metanephric kidneys, the nephrogenic zone of the metanephric kidney being present
      from 35 to 96 days postpartum. No new nephrons were formed after day 96. After
      the completion of nephrogenesis, the kidney increases in size through glomerular
      and tubular growth. The sequence of steps in the development of the possum skin
      was identical to that observed in other marsupials. The epidermis of the possum
      was thickest at 60 microns on about day 28 postpartum and as development
      proceeded the epidermis gradually decreased in thickness. A sparse number of
      primordia of hair follicles were observed at day 10 and the possum had a good
      covering of hair by day 129 postpartum. Correlation between the development of
      the lung, kidney and skin with the previously published plasma thyroxine
      concentration in the young possum suggests that thyroxine from the mother and
      from the young is important in the development of these three organs.

PMID- 9522894
TI  - Developmental study of the round window region.
AB  - A silicone impression method to study the anatomy of the round window region was
      used in 102 temporal bones belonging to individuals aged from 4 months of fetal
      life to 3-year-old children as well as adults. A total of 2,142 measurements of
      the round window, oval window and round window fossula was made in the molds. The
      data demonstrate that the round window shows a diameter from 1.21 mm (average for
      the short axis) to 1.74 mm (average for the long axis) and the circular shape was
      present in 55% of the adult temporal bones and in 18.18% of the fetal and
      infantile ones. The adult dimensions of the measured structures are reached
      during fetal development.

PMID- 9522895
TI  - Anchoring and support system of pulmonary gas-exchange tissue in four bird
      species.
AB  - Avian air capillaries are delicate structures compared to the mammalian pulmonary
      alveolus. A transmission and scanning electron microscopic study was carried out
      on several species of birds with the aim of determining the support structures of
      the avian gas-exchange mantle. Lung tissue of two bird species belonging to
      strong flying birds (pigeon and barn owl) and two relatively flightless species
      (domestic fowl and quail) was subjected to standard processing for transmission
      and scanning electron microscopy after intratracheal inflation. Twisted profiles
      of lipoproteinaceous trilaminar substance as specific secretory product of avian
      squamous respiratory cells can be seen in the cell body and cytoplasmic
      extensions that are wedged between the blood capillaries, partly surrounding
      them. The intracytoplasmatically located trilaminar complexes form a three
      dimensional intricate spiderweb-like system between the blood capillaries and air
      capillaries, which presumably function as an anchoring and support structure of
      the gas-exchange tissue. This system is strengthened by retinacula--pairs of
      attenuated parallel processes of squamous respiratory cells that project to the
      airway lumen--expanding and bridging the opposite side of air capillaries. The
      trilaminar substance is discharged in the form of a 15-nm-thick acellular lining
      layer which is uniquely adapted to the extremely thin respiratory epithelium. The
      trilaminar substance arises in the cytoplasm of squamous respiratory cells from
      profiles of granular and smooth endoplasmic reticulum. The integrity and
      stability of the gas-exchange tissue is likely to be guaranteed by a specific
      arrangement of the squamous respiratory cells, in which the trilaminar substance
      plays a paramount role. This general pattern can be observed in strong flying
      bird species as in the relatively flightless birds.

PMID- 9522897
TI  - Cartilage and synovium of the human atlanto-odontoid joint. An anatomic and
      histological study.
AB  - The surface area, thickness and composition of articular cartilage of the atlanto
      odontoid joints were investigated in twenty human cadaveric cervical spine
      specimens. The specimens were also examined grossly and by light microscopy to
      determine the location of the synovium. The anterior arch of the atlas and
      ventral and dorsal articular surfaces of the dens were covered with hyaline
      cartilage. The mean values of the articular surface areas on the ventral surface
      of the dens and anterior arch of the atlas were 55.10 and 58.24 mm2,
      respectively. The mean thickness of the articular cartilage of the anterior arch
      of the atlas, ventral and dorsal surfaces of the dens was 0.80, 0.81 and 0.82 mm,
      respectively. Synovial membranes were associated with the joint capsules and
      surrounding tissues of both anterior and posterior atlanto-odontoid joint spaces,
      where the synovial membranes were attached to the margins of the articular
      surfaces of the dens and anterior arch of the atlas anteriorly and the region of
      the cruciate ligament immediately peripheral to the cartilage region apposed to
      the dens and dens cartilage itself, posteriorly.

PMID- 9522896
TI  - Effects of continuous or cyclic administration of pamidronate on the skeleton in
      intact and oophorectomized young rats.
AB  - Bisphosphonates are potent inhibitors of bone resorption, and are therefore used
      for the treatment of various bone diseases including osteoporosis. We examined
      whether cyclic therapy with bisphosphonates in oophorectomized osteoporotic rats
      had any advantage over continuous treatment. We therefore treated intact and
      oophorectomized young female rats for 8 weeks with 1 and 5 mg/kg/day of
      pamidronate. The 8-week treatment was given continuously for 6 days/week or
      intermittently, i.e. 6 days of pamidronate (APD) and 3 weeks off, for 2 cycles.
      We found an increase in tibial wet and ash weight and in the mineral content in
      oophorectomized rats treated continuously or intermittently with APD in
      comparison to nontreated oophorectomized animals. Histomorphometric analysis
      showed an increase in the volume of metaphyseal cartilage and bone. No changes
      were found in the volume of epiphyseal or diaphyseal bone. Pamidronate had very
      little effect on the bone of intact rats. Pamidronate seems to be more effective
      in inhibiting bone resorption in bone that undergoes rapid turnover (i.e. in
      oophorectomized animals) when compared to bone with low turnover (intact rats).
      Although the results of cyclic treatment were similar to those of continuous
      treatment, we have to remember that cyclic therapy may be more advantageous since
      animals receiving cyclic therapy received only 25% of the dose of rats
      continuously treated.

PMID- 9522898
TI  - Accessory extensor carpi radialis muscle and interconnecting muscular bundle.
AB  - An accessory muscle and a muscular bundle were found and prepared in both
      forearms of a 55-year-old male cadaver. On the left side, the accessory muscle
      originated from the medial aspect of the extensor carpi radialis brevis (ECRB)
      muscle, coursed downwards, crossed posterior to the tendon of ECRB, passed
      through the second chamber of the extensor retinaculum and inserted into the base
      of second metacarpal bone. Additionally, a muscular bundle was observed between
      the extensor carpi radialis longus (ECRL) and ECRB muscles. On the right side,
      both ECRL and ECRB had bifid tendons. The long and thin additional tendon of ECRL
      coursed downwards and joined the accessory tendon of the ECRB before entering the
      second chamber of the extensor retinaculum and the common tendon inserted into
      the base of the second metacarpal bone.

PMID- 9522899
TI  - Function and structure in early modern muscular mechanics. Four episodes and a
      dialogue between Stensen and Borelli on two chief muscular systems.
AB  - The dispute on the movement of skeletal muscles in 1667 between Giovanni Alfonso
      Borelli, who maintained the ancient movement caused by inflation theory, and
      Niels Stensen (Nicolaus Steno), who proposed the first recorded theory of fibre
      contraction, had far reaching implications for understanding the relation between
      muscle morphology and function. A dialogue is reconstructed from citations from
      the two authors' main works. They had a similar dispute on the movement of the
      heart along the lines of the debate in the 1630s between William Harvey favouring
      contraction and Rene Descartes favouring swelling. Evidence is provided for the
      delayed general acceptance of fibre contraction in both heart and skeletal
      muscles. It is shown that the inflation interpretation of muscular mechanics
      elaborated by Borelli, Johann Bernoulli, his son Daniel, and by others, was
      maintained from ancient authors and Descartes in part due to a conceptual block
      resulting from the mechanical philosophy that denied any force of attraction in
      nature. The alternative theory, that of fibre contraction, was thought of as self
      motion, which violated an accepted mechanical principle and therefore was
      rejected. In the mid-18th century, Albrecht von Haller recorded no microscopic
      structures in support of inflation. He adopted the view that contraction in
      fibres of muscles is generated through an 'irritability'. Research on this entity
      has taken place ever since with a clear preponderance of studies on single fibre
      properties and subcellular structures. Haller did not, however, refer to the
      original contribution of Stensen on fibre contraction. Haller even rejected
      Stensen's functional architecture of skeletal muscle. This structure, now called
      the unipennate, or semipennate, actuator, was overlooked and had to await
      confirmation by anatomical rediscovery and pragmatic demonstration through
      successful applications in computer models of muscular contraction in the 1980s.

PMID- 9522901
TI  - Prevention of local scar formation after operative discectomy for lumbar disc
      herniation.
AB  - This was a prospective study. The study evaluated the use of Preclude Spinal
      Membrane to inhibit peridural fibrosis and reduce fibroses-related problems after
      first-time lumbar discectomy. Peridural scarring causes tethering of dura and
      nerve roots. Following discectomy Preclude Spinal Membrane was applied to
      patients of first group (10 patients). The second group (10 patients) was
      operated on without Preclude Spinal Membrane. Outcome was evaluated with MRI, 3
      and 6 month after operation for all patients. No peridural or epidural scar
      tissue could be found in patients with Preclude Spinal Membrane, in the control
      group who were operated on without the preclude Spinal Membrane scar tissue of
      varying degree with complete enclosure of the nerve roots and dura was found.

PMID- 9522900
TI  - Anterior interbody fusion with the BAK-cage in cervical spondylosis.
AB  - BAK-C is a new autostabilizing interbody cage which is implanted during an
      anterior cervical procedure to provide stability to the motion segment and allow
      fusion to occur. Special instrumentation is provided with a bone collecting
      reamer. The system utilizes surgical site bone graft as the osteo-inductive
      material within the implant. Biomechanical testing indicates improved stability
      and animal studies show good fusion. The basic principle is distraction
      compression using the tension forces of the annulus fibrosus. Operative material
      concerns a two years experience with 80 patients (101 levels), 72 with cervical
      radiculopathy, 8 with myelopathy. Clinical evaluation is assessed on a ten point
      analogue pain scale for neck and arm/shoulder pain, with neurological
      examination. Radiological evaluation includes dynamic X-rays, myelo-CT and MRI.
      Patients are re-evaluated at 1, 6, 12 months postoperatively. Results for neck
      and radicular pain is excellent, but neurological recovery for radiculopathy and
      myelopathy is quite different. Radiological results are also good with (except
      one case) no instability, no cage migration, no kyphosis, no pseudarthrosis. Bone
      fusion is assessed at 6 and 12 months. Complications are few with proper
      technique, mainly correct distraction, symmetrical endplate drilling and lateral
      X-ray control. Only one patient needed an early re-operation with additional
      miniplate fixation. Immediate stability with good clinical response and no graft
      morbidity are the advantages of this implant compared to conventional cervical
      interbody grafting techniques.

PMID- 9522902
TI  - Analysis of fluid in cysts accompanying various primary and metastatic brain
      tumours: proteins, lactate and pH.
AB  - There is a growing interest in cystic lesions of the brain. By examining the cyst
      content of brain tumours more insight into the pathogenesis of cyst formation has
      been found. In this study, 39 samples of cyst fluid of 34 patients with a cyst
      accompanying a brain tumour were collected and studied biochemically regarding
      their protein content, lactate and pH. In this study we investigated the relation
      between the grade of malignancy and the lactate-concentration and the discrepancy
      between the high levels of lactate in cysts and their alkaline environment. The
      results of the measurements of the concentrations of albumin, immunoglobulines
      (IgG, IgA, IgM) and alpha 2-macroglobulin in cysts compared to those in sera
      suggest that cyst formation associated with tumour is based upon a disruption of
      the blood-brain barrier with exudation of plasma proteins into the brain
      parenchyma resulting in accumulation of fluid (oedema) and eventually in
      formation of a cyst. There appears to be a positive relation between the grade of
      malignancy and the concentration of lactate in the cysts with a significant 2
      fold increase in lactate concentration in malignant tumour cysts compared to the
      more benign tumour cysts (p < 0.001) probably on account of aerobic glycolysis
      with production of lactate by the tumour. The measured pH values in the cysts
      were above normal, resulting in a discrepancy of the high levels of lactate in
      the cyst with the alkaline environment and this suggests efflux of H(+)-ions by a
      Na/H exchange mechanism to compensate for the change of pH.

PMID- 9522903
TI  - Multilobular cavernous malformation: report of two cases.
AB  - The authors report two cases of cavernous malformation characterized by a
      multilobular appearance on magnetic resonance images. At surgery, the
      malformations consisted of several nests of angiomatous components that were
      separated by intervening brain tissue and connected with each other by tiny
      vessels. This basic configuration seems to explain the unexpected postoperative
      recurrence of cavernous malformations and/or rebleeding from the residual
      lesions.

PMID- 9522904
TI  - Proliferative potential of recurrent intracranial meningiomas as evaluated by
      labelling indices of BUdR and Ki-67, and tumour doubling time.
AB  - This study was designed to provide the reciprocal relationship among labelling
      indices of 5-bromodeoxyuridine (BUdR LI), Ki-67 (Ki-LI), and tumour doubling time
      (Td) of recurrent meningiomas. In our series of 182 primary intracranial
      meningiomas, 46 cases recurred. The average of BUdR LI and Ki LI for nonrecurrent
      meningiomas were 0.77 +/- 0.13% and 4.71 +/- 1.96%, respectively. Recurrent
      meningiomas had significantly higher LIs at the first operation: BUdR LI was 3.77
      +/- 1.22% and Ki LI was 14.78 +/- 3.17%. The recurrent ratio significantly
      increased with the degrees of each LI. And the linear regression analysis has
      demonstrated a significant correlation between BUdR and Ki LI. Td was calculated
      accurately by NIH, a computer software. Td showed a significant inverse
      correlation with each of the labelling indices. Consequently, BUdR, Ki LIs and Td
      of individual tumours correlate mutually well. Of the 46 recurrent cases, 4
      received radiation after the operation. Td of the irradiated meningiomas tended
      to be longer than expected for their higher level of BUdR and Ki LIs before
      radiation therapy. Thus, it was shown that the radiation therapy delays the
      regrowth of meningiomas.

PMID- 9522905
TI  - Craniofacial access in children.
AB  - We have used craniofacial access in 20 children (age range 3/12-14 years) for
      complex skull base/intracranial pathology over the past 5 years. The majority of
      the patients had a tumour-7 of the skull base, 5 extensive suprasellar lesions
      and 3 acoustic neuromas; 4 had an aneurysm or AVM and in 1 there was a congenital
      problem. This extended application of established adult techniques in a
      paediatric practice emphasises the fundamental point that the quintessence of
      good surgical practice is the construction of an operation for the individual
      patient's pathology. We therefore used transzygomatic, orbital, transoral,
      transmandibular, petrous, transcondylar, translabyrinthine and transbasal access
      techniques. Good function and cosmesis with minimal complications were achieved.
      We have not observed complications with craniofacial growth and the majority of
      patients were able to return to normal school. The range of approaches used
      emphasise the importance of a multidisciplinary team with both paediatric and
      neurosurgical expertise, especially with complex vascular and skull base
      pathology, in dealing with these difficult problems. The case for specialist
      referral merits some discussion within the representative bodies of paediatric
      neurosurgeons.

PMID- 9522906
TI  - Diffuse axonal injury (DAI) is not associated with elevated intracranial pressure
      (ICP).
AB  - OBJECTIVE: Traditionally, intracranial pressure (ICP) monitoring has been
      utilized in all patients with severe head injury (Glasgow coma score of 3-8).
      Ventriculostomy placement, however, does carry a 4 to 10 percent complication
      rate consisting mostly of hematoma and infection. The authors propose that a
      subgroup of patients presenting with severe head trauma and diffuse axonal injury
      without associated mass lesion, do not need ICP monitoring. Additionally, the
      monitoring data from ICP, MAP, and CPP for a comparison severe head injury group,
      and subgroups of DAI would be presented. MATERIALS AND METHODS: Thirty-six
      patients sustaining blunt head trauma and fitting our strict clinical and
      radiographic diagnosis of DAI were enrolled in our study. Inclusion criteria were
      severe head injury patients who did not regain consciousness after the initial
      impact, and whose CT scan demonstrated characteristic punctate hemorrhages of <
      10 mm diameter at the greywhite junction, basal ganglia, corpus callosum, upper
      brainstem, or a combination of the above. Patients with significant mass lesions
      and documented anoxia were excluded. Their intracranial pressure (ICP) and
      cerebral perfusion pressure (CPP) were compared to a control group of 36
      consecutive patients with severe non-penetrating non-operative head injury, using
      the Analysis for Variance method. RESULTS: Eighteen (50.0%), six (16.7%), and
      twelve (33.3%) patients had types I, II, and III DAI, respectively. The admission
      Glasgow Coma Score (GCS) was higher for types I and II than for type III DAI. ICP
      was monitored from 23 to 165 hours, with a mean ICP for 36 patients of 11.70 mmHg
      (SEM = 0.75) and a range from 4.3 to 17.3 mmHg. Of all ICP recordings, of which
      89.7%, (2421/2698) were < or = 20 mmHg. Average mean arterial pressure (MAP) was
      96.08 mmHg (SEM = 1.69), and 94.6% (2038/2154) of all MAP readings were greater
      than 80 mmHg. Average cerebral perfusion pressure (CPP) was 85.16 mmHg (SEM =
      1.68), and 90.1% (1941/2154) of all CPP readings were greater than 70 mmHg. This
      is compared to the control group mean ICP, MAP, and CPP of 16.84 mmHg (p =
      0.000021), 92.80 mmHg (p = 0.18), and 76.49 mmHg (p = 0.0012). No treatment for
      sustained elevated ICP > 20 mmHg was needed for DAI patients except in two; one
      with extensive intraventricular and subarachnoid hemorrhage who developed
      communicating hydrocephalus, and another with ventriculitis requiring intrathecal
      and intravenous antibiotic treatments. Two complications, one from a catheter
      tract hematoma, and another with Staph epidermidis ventriculitis, were
      encountered. All patients, except type III DAI, generally demonstrated marked
      clinical improvement with time. The outcome, as measured by Glasgow Coma Score
      (GCS) and Glasgow Outcome Score (GOS) was similarly better with types I and II
      than type III DAI. CONCLUSION: The authors conclude that ICP elevation in DAI
      patients without associated mass lesions is not as prevalent as other severe head
      injured patients, therefore ICP monitoring may not be as critical. The presence
      of an ICP monitoring device may contribute to increased morbidity. Of key
      importance, however, is an accurate clinical history and interpretation of the CT
      scan.

PMID- 9522907
TI  - Spontaneous intracranial hypotension associated with subdural hematoma:
      diagnostic usefulness of percutaneous subdural tapping and magnetic resonance
      imaging.
AB  - A 55-year-old woman presented with headache which was characterized by
      aggravation in the upright position and relief in recumbency. Although
      intracranial hypotension syndrome was considered to be the most-likely possible
      entity, computed tomography (CT) scans demonstrated subdural fluid collections
      associated with findings reminiscent of transtentorial herniation. Because of
      these CT features, cerebrospinal fluid pressure measurement by a lumbar puncture
      was not performed. In stead, as an alternative method, she underwent percutaneous
      subdural tapping, which failed to obtain spontaneous drainage of liquid
      haematoma, indicating intracranial hypotension. In addition, gadolinium-enhanced
      magnetic resonance imaging study performed later supported the diagnosis of
      spontaneous intracranial hypotension. Thus, the usefulness and safety of
      percutaneous subdural tapping for the diagnosis of spontaneous intracranial
      hypotension is stressed.

PMID- 9522908
TI  - Inflammatory cytokines locally elevated in chronic subdural haematoma.
AB  - The involvement of inflammation in the development and propagation of chronic
      subdural haematoma (CSH) was investigated by measuring the levels of inflammatory
      cytokines (tumour necrosis factor [TNF] alpha, interleukin [IL]-1 beta, IL-6, and
      IL-8). Peripheral venous blood and subdural fluid were obtained at the time of
      burr hole surgery from 34 patients with CSH and from 9 with subdural effusion.
      The levels of the inflammatory cytokines were analysed by enzyme-linked
      immunosorbent assay. The blood levels of TNF alpha, IL-1 beta, IL-6, and IL-8 in
      both CSH and subdural effusion groups were almost within the range of normal
      subjects, and no differences were observed between the two groups. IL-6 and IL-8
      in the subdural fluid were much higher than in the blood of both groups, and the
      levels in CSH patients were significantly higher (10 times) than in subdural
      effusion patients. Local elevation of inflammatory cytokines in the subdural
      space of both CSH and subdural effusion without systemic change suggests the
      presence of local inflammation in the two diseases. The same behavioural patterns
      of cytokines for these and higher levels of cytokines in the CSH also suggest
      that inflammatory cytokines may be involved in the continuous development from
      subdural effusion to CSH and propagation of CSH.

PMID- 9522909
TI  - Management of minor head injuries: admission criteria, radiological evaluation
      and treatment of complications.
AB  - The clinical course of patients admitted following minor head injuries (Glasgow
      Coma Score [GCS] 13-15) has been studied less extensively than in severely head
      injured patients. Admission criteria, methods and indications for radiological
      evaluation are controversial. To study this further, a retrospective review of
      633 patients admitted following such injuries to King Khalid University Hospital
      between 1986 and 1993 was undertaken. Their ages ranged from one month to 80
      years (average 17 years). The mechanisms of injury were mainly falls in 339
      (53.5%) cases and road traffic accidents in 234 (37%). None of the cases resulted
      from a non-accidental injury. Radiological evaluation was by skull radiography in
      616 (97.3%) cases followed by CT scan in 131 (20.7%). These studies revealed a
      skull fracture in 78 (12.7%) cases. Six of these 78 patients with skull fracture
      required a neurosurgical procedure during the first week post injury. These
      represented 0.97% of the cases who had skull radiographs. A base of skull
      fracture was an ominous sign, since 3 of the 5 cases with such fractures required
      ventilation of which one resulted in the only mortality of this series, the
      fourth developed meningitis. Of the cases studied, 3 (0.5%) developed growing
      skull fractures all had the initial injury during their first year of life. Other
      complications were as follows: 25 (3.9%) early post-traumatic seizures, 10 (1.6%)
      chronic subdural haematomas, 9 (1.4%) extradural haematomas, 2 (0.3%) post
      traumatic hydrocephalus and one (0.2%) cerebral abscess. We conclude that
      patients who have an abnormal GCS, a neurological deficit, post-traumatic
      seizure, signs or suspicion of basal or depressed skull fracture should be
      admitted for observation because of the risk of deterioration. Patients with a
      history of loss of consciousness or amnesia without any of the previous may be
      discharged to be observed at home by a competent observer, otherwise, will need
      admission for observation. Radiological evaluation once indicated must be by CT
      scan. There is no benefit from immediate skull radiography in the initial
      evaluation of minor head injuries. The indications for CT are an abnormal GCS,
      presence of neurological deficit, signs of basilar or depressed fracture and
      persistent or progressive headache or vomiting. Infants with minor injuries
      should be followed up at least once after two to three months for possible
      growing fractures.

PMID- 9522911
TI  - The breast: a concealed site for implanting a morphine pump.

PMID- 9522912
TI  - Experimental traumatic cerebral contusion: morphological study of brain
      microvessels and characterization of the oedema.
AB  - Several experimental brain oedema models are currently available, but most of
      them are very different from what happens in clinical practice. As it is simple
      and seems to replicate the range of injuries seen in man we decided to evaluate
      Marmarou's model of head injury in order to test physiopathogenic and therapeutic
      hypotheses. Three groups of Wistar rats weighting 360-400 gr, anaesthetized with
      sodium pentobarbitone and breathing spontaneously, without tracheal intubation,
      were studied. In the first group six animals were killed two hours after injury
      and the brain's water content compared with that of nine controls. In another
      group Evans blue (100 mg/kg) was injected one hour before trauma and dye's
      extraction ratio determined at various times after injury: five animals at 15
      minutes, six at 30 minutes, five at 60 minutes and nine at 120 minutes. A total
      of twenty-eight animals served as controls. In the last group morphological
      studies with light and electron microscopy were performed in the traumatized
      brain tissue from rats killed 5 and 120 minutes after injury and in brain tissue
      from control rats. Results showed that Marmarou's brain trauma model induced
      perivascular brain oedema, already visible at the ultrastructural level 5 minutes
      after the injury. Endothelial cells themselves were "oedematiated", rich in
      pinocytotic vesicles and membrane blebs, and presented intact tight junctions.
      Two hours after trauma the perivascular oedema was more marked. At this time the
      brain water content was significantly higher than that in controls. Evans blue
      extraction ratio increased linearly with time, being significantly higher than in
      controls 120 minutes after injury. We conclude that Marmarou's model is a
      suitable model for the study of brain oedema induced by trauma, and that this
      oedema, assessed by three different methodologies, was statistically significant
      two hours after injury.

PMID- 9522910
TI  - The value of long-term clinical follow-up for cases of spontaneous carotid
      cavernous fistula.
AB  - To clarify the value of clinical long-term follow-up with radiological
      examination, ranging from 12 to 63 months (average: 35 months), 18 consecutive
      patients suffering from spontaneous carotid cavernous fistula (CCF), were studied
      prospectively. Five aged patients without aggressive symptoms were treated
      conservatively, and the other 13 underwent transarterial embolization. The
      radiological follow-up was primarily by magnetic resonance angiography (MRA),
      performed from 2 to 6 times (average: 4.1 times) during the follow-up period. In
      three cases, CCFs persisted, but the other fifteen (83%) demonstrated complete
      cure as defined by long-term follow-up MRA. The three patients with persistent
      CCFs were comparatively young, less than 60 years old, had no atherosclerotic
      factors and demonstrated multiple venous drainage routes with cortical venous
      drainage on angiography. In two of them, the symptoms completely disappeared, and
      the other had only mild chemosis. However, surprisingly, in two, MRA revealed
      residual CCF with drainage into only cortical veins through the sphenoparietal
      sinus, this radiological finding being well known to signify danger. During the
      follow-up period, central retinal vein thrombosis occurred in two cases. The
      common point in these cases was that the superior ophthalmic vein was the only
      venous drainage route. This is also a point requiring care. We therefore
      emphasize the importance of careful long-term radiological follow-up for
      spontaneous CCF patients even when their symptoms improve or disappear. MRA is
      particularly suitable for this purpose and applicable in the out-patient clinic
      because of its non-invasive nature.

PMID- 9522913
TI  - The effect of oestrogen on the development of arteriovenous fistulae induced by
      venous hypertension in rats.
AB  - PURPOSE: Dural arteriovenous fistulae (AVF) represent abnormal communication
      between the meningeal arteries and the dural sinuses. Clinically, this condition
      appears more frequently in post-menopausal and pregnant women than in the general
      population. Oestrogen is believed to play an important role in the development of
      dural AVF; however, its exact role has not been clearly defined. We have
      previously reported that by surgically creating a carotid-jugular shunt in male
      rats, which then induces venous hypertension, spontaneous arteriovenous fistulae
      can result. To examine the specific role that oestrogen may have in the
      development of AVF induced by venous hypertension, we performed the following
      experimental procedure. MATERIALS AND METHODS: Ninety-four Sprague-Dawley female
      rats (250-300 grams in weight) were randomly assigned to four different groups.
      Group 1 (n = 20): control (bilateral ovariectomy only). Group 2 (n = 19):
      bilateral ovariectomy and implantation of the oestrogen pellet (17-beta
      oestradiol 0.75 mg/pellet, 60 days release). Group 3 (n = 17): bilateral
      ovariectomy and venous hypertension (left carotid-jugular shunt with proximal
      jugular vein occlusion). Group 4 (n = 38): bilateral ovariectomy and oestrogen
      pellet implantation and venous hypertension. All of the groups were examined by
      angiography 60 days after treatment. In Groups 1 and 2, bilateral common carotid
      angiography was performed via a transfemoral route. In Groups 3 and 4,
      angiography was done after surgical ligation of the carotid-jugular shunt to
      examine for any newly developed AVF. RESULTS: No newly developed AVF were found
      in either Groups 1, 2, or 3. In Group 4, 2 rats (5.3%) developed newly formed AVF
      which occurred in the nose and neck. Our previous study demonstrated that AVF
      appeared in 3 of 22 (13.6%) venous hypertensive male rats. Therefore, no
      statistical difference in the appearance rate of newly formed AVF was found among
      groups 1, 2, 3 or 4 and between our previously reported group of male venous
      hypertensive rats. CONCLUSION: In this experimental study, ovariectomy with or
      without oestrogen did not affect the development of spontaneous AVF induced by
      venous hypertension.

PMID- 9522914
TI  - The use of cardiac troponin-I (cTnI) to determine the incidence of myocardial
      ischemia and injury in patients with aneurysmal and presumed aneurysmal
      subarachnoid hemorrhage.
AB  - A prospective single center study was performed to determine the minimal
      preoperative incidence of unrecognized cardiac injury in patients suffering
      aneurysmal and presumed aneurysmal subarachnoid hemorrhage (SAH). When caring for
      such patients in the pre- and post operative period clinicians must be aware of
      the possibility of cardiac injury even when a history of previous cardiac
      symptomatology is not present. Forty-seven consecutive patients suffering from
      SAH over a five-month period underwent serum measurements of the cardiac muscle
      marker troponin I (cTnI) immediately upon admission. Repeat studies, if possible,
      were done 24 hours later. EKG was performed in all patients and was available for
      review in 44 of the 47 cases. Echocardiography was performed in four of eight
      patients with elevated cTnI levels. Signs and symptoms relating to cardiac
      ischemia were recorded by the patients' physicians and nurses. Eight individuals
      (17%) had elevations in cardiac troponin I levels. Because surgical treatment is
      generally carried out as soon as possible following the hemorrhage, many patients
      with normal troponin I levels within twenty-four hours of their hemorrhage were
      operated upon before a repeat enzyme could be obtained or possibly before
      elevations could be recorded. In addition, a number of patients were referred to
      our center several days post-hemorrhage at a time when marker levels may have
      normalized. Therefore, the 17% incidence of elevated cTnI may be an
      underestimate. Only two of the eight patients had clinical abnormalities in
      cardiac function. Four patients with elevated levels had echocardiograms, three
      of which were abnormal. One additional patient died of a myocardial infarction
      before an echocardiogram could be obtained. EKG was abnormal in six of the seven
      patients with elevated troponin who had tracings available for review. Recordings
      consistent with recent myocardial ischemia were present in four of these. Of the
      39 patients with negative troponin I levels, 37 had EKG available for review.
      None had recordings clearly consistent with recent myocardial ischemia although
      13 were suggestive of ischemic changes. None of these 39 patients had pre- or
      post-operative clinical changes in cardiac function. Elevations in troponin I
      appeared to be unrelated to the patient's Hunt and Hess grade or Fisher score
      although our numbers were too small to draw any meaningful conclusions.

PMID- 9522915
TI  - Delayed hearing loss after microvascular decompression of the trigeminal nerve.
AB  - OBJECTIVE: The development of sudden postoperative hearing loss as a complication
      of microvascular decompression (MVD) operations in the cerebellopontine angle has
      already been reported. A sudden hearing loss of vascular origin may also occur
      hours or days after such operations, but even in such cases an improvement of
      hearing over the following weeks is possible. Here we report on a gradual
      deterioration of hearing over a period of two weeks after MVD which has not been
      described in the literature up to now. CLINICAL PRESENTATION: A MVD operation was
      performed twice on a 36 year old patient with trigeminal neuralgia. After the
      second operation the patient developed a slight hearing impairment 3 days
      postoperatively which increased over a period of two weeks and ended up with
      total deafness. The course of intra-operative brainstem auditory evoked
      potentials and postoperative audiograms is documented. CONCLUSION: Because of
      gradual development of the delayed hearing loss, we conclude that postoperative
      tissue scarring may be the underlying pathology.

PMID- 9522917
TI  - Extensive parasellar chondroma with Ollier's disease.

PMID- 9522916
TI  - Acute encephalopathy after iohexol ventriculography in functional stereotaxy.

PMID- 9522920
TI  - Federal program, higher administration fees boost vaccination rates, study shows.

PMID- 9522919
TI  - Report tracks HMO pharmacy cost, benefit trends.

PMID- 9522918
TI  - Intraclinoidal ophthalmic artery aneurysm.

PMID- 9522921
TI  - FDA sets policy on industry-sponsored educational programs.

PMID- 9522922
TI  - Texas Society rebuts antisubstitution articles.

PMID- 9522923
TI  - Expiration and beyond-use dates.

PMID- 9522924
TI  - Setting up the herbal formulary system for an alternative medicine clinic.

PMID- 9522925
TI  - Working in a latex-safe environment.

PMID- 9522926
TI  - Transition to managed care, Part 3.

PMID- 9522927
TI  - Anastrozole: a selective aromatase inhibitor for the treatment of breast cancer.
AB  - The role of anastrozole, a new selective aromatase inhibitor, in treating hormone
      responsive metastatic breast cancer is discussed. Treatment options for hormone
      dependent breast cancer focus on interfering with the endocrine system in an
      attempt to modify the effects of estrogen. Tamoxifen is the drug of choice for
      primary endocrine therapy, but there is a need for agents with similar or greater
      efficacy and better tolerability. Anastrozole inhibits the conversion of
      androgens to estrogens by aromatase. Bioavailability studies have demonstrated
      almost complete absorption of anastrozole after oral administration. The drug's
      terminal half-life after multiple doses is 50 hours. Anastrozole is cleared
      principally by the liver. Clinical trials comparing anastrozole with megestrol
      acetate demonstrated no significant differences in clinical efficacy, although a
      follow-up study revealed a longer median overall survival rate in patients
      receiving anastrozole. The drug is well tolerated. Among the most frequently
      reported adverse effects are asthenia, hot flashes, headache, and back pain. The
      recommended dosage is 1 mg daily. The average wholesale cost of month's supply of
      anastrozole is $187.20, compared with approximately $100 for generic megestrol
      acetate or aminoglutethimide plus hydrocortisone. Although anastrozole will
      likely become the preferred second-line agent in the treatment of postmenopausal
      breast cancer in patients with disease progression after tamoxifen therapy, it is
      not a therapeutic alternative to aminoglutethimide on the basis of approved
      indications. Anastrozole and other aromatase inhibitors may have multiple
      applications in treating hormone-responsive breast cancer.

PMID- 9522928
TI  - Development of an interdisciplinary, telephone-based care program.
AB  - An interdisciplinary, telephone-based care program at a Veterans Affairs medical
      center (VAMC) is described. Patients telephoning the Oklahoma City VAMC
      complained that they were transferred multiple times and that they had difficulty
      contacting their provider between scheduled visits. Some went to the walk-in
      urgent care clinic with nonurgent problems. The average waiting time in the
      clinic exceeded three hours. An interdisciplinary, telephone-based care program
      was begun in 1995 to allow efficient problem resolution over the telephone;
      provide clinical consultations, interventions, and referrals as necessary; and
      reduce use of the urgent care clinic for nonurgent problems. A team consisting of
      a patient service representative, a pharmacist, and a nurse was established to
      handle calls. Policies and procedures were designed to respond appropriately to
      patients' problems and document the telephone "visits." The pharmacist was given
      practice privileges, including prescribing authority. A questionnaire indicated
      patient satisfaction with the new service. Mean waiting times in the urgent care
      clinic were reduced to less than two hours, and an estimated annual net cost
      avoidance of $677,671 was achieved by the program's averting unnecessary visits
      to the urgent care clinic. An interdisciplinary, telephone-based care program at
      a VAMC successfully responded to patients' concerns, improved their access to
      care, and conserved urgent care resources.

PMID- 9522929
TI  - Design, construction, implementation, and cost of a hospital pharmacy cleanroom.

PMID- 9522930
TI  - Storage of extemporaneously prepared ophthalmic antimicrobial solutions.
AB  - The feasibility of long-term storage of commonly used ophthalmic antimicrobial
      solutions was studied. Solutions of tobramycin 15 mg/mL (as the sulfate salt),
      cefazolin 33 mg/mL (as the sodium salt), and vancomycin 50 mg/mL (as the
      hydrochloride salt), each in artificial tears, were prepared with aseptic
      technique. Ten 15-mL portions of each solution were prepared; five of each were
      stored at 4 degrees C and the other five at 25 degrees C. Samples of each portion
      were tested before storage and 7, 14, 21, and 28 days after preparation for
      osmolality, pH, and antimicrobial activity. For the tobramycin solution there
      were no differences in osmolality or the zone of inhibition associated with
      temperature or time. The pH dropped between days 0 and 7 at both temperatures.
      For the cefazolin solution there were no differences in osmolality associated
      with temperature or time. The pH was higher in portions stored at 25 degrees C
      than at 4 degrees C and increased over time in portions stored at either
      temperature. The zone of inhibition was larger for portions stored at 4 degrees C
      than at 25 degrees C but did not change over time. For the vancomycin solution
      there were no differences in osmolality associated with temperature or time. The
      pH did not differ between portions stored at 4 and 25 degrees C but dropped
      sharply at both temperatures between days 0 and 7. The zone of inhibition did not
      differ with temperature or time. The tobramycin solution could be stored for 28
      days at room temperature and the cefazolin solution for 28 days under
      refrigeration. The pH of the vancomycin solution changed too quickly for storage
      to be recommended.

PMID- 9522932
TI  - Disease management in the alternate-site health care setting.
AB  - The role of pharmacies that specialize in the treatment of specific chronic
      diseases in the alternate-site health care setting is discussed. The optimal use
      of medications through disease management programs can improve patient outcomes
      and lower overall health care costs. The increase in disease management programs
      has spawned the growth of disease-specific pharmacies in the home care and other
      alternate-site health care settings. These pharmacies usually operate from a
      single location or are regionalized operations that deliver pharmaceutical
      products to patients throughout the United States. The pharmacies employ
      clinicians who specialize in a particular disease. These clinicians conduct
      comprehensive patient education programs, drug-use review, and compliance
      monitoring. Disease management pharmacies focus on chronic, expensive diseases;
      costs related to inventory, equipment, and storage can be very high. Many disease
      management pharmacies are involved in preferred-distribution or closed
      distribution arrangements with pharmaceutical manufacturers. Pharmacists involved
      in disease management programs routinely send compliance information about their
      patients to pharmaceutical companies, managed care organizations, or prescribing
      physicians. Disease management pharmacies act as advocates for patients with
      particular chronic diseases. Various foundations and patient advocacy and
      research groups have created their own disease management pharmacies. Disease
      management has also reached the community pharmacy practice setting. Pharmacies
      specializing in the treatment of specific chronic diseases in the alternate-site
      health care setting can improve health care and promote efficient use of health
      care dollars.

PMID- 9522931
TI  - Stability of undiluted and diluted adenosine at three temperatures in syringes
      and bags.
AB  - The stability of adenosine in various diluents in polypropylene syringes and
      polyvinyl chloride (PVC) bags at three temperatures was studied. Portions of
      pooled undiluted adenosine infusion (3 mg/ mL) were stored in 60-mL capped
      syringes, 20 for each storage condition. Adenosine infusions were prepared by
      mixing adenosine with 5% dextrose injection, 0.9% sodium chloride injection,
      lactated Ringer's injection, or 5% dextrose and lactated Ringer's injection to
      produce a concentration of 0.75 mg/mL. Samples of each infusion were stored in 60
      mL capped syringes and 50-mL bags, 20 syringes and 20 bags for each storage
      condition. Syringes and bags were stored in the dark at 25, 5, and -15 degrees C.
      At various sampling times, three syringes and three bags of each infusion were
      removed for visual inspection, pH measurement, and high-performance liquid
      chromatographic analysis. At 10 and 16 days, fungal growth at 25 degrees C was
      suspected in the infusions prepared with 5% dextrose injection. For all other
      samples, there was no evidence of precipitation or change in pH. The
      concentration of adenosine remained constant in all samples at all storage
      conditions. Adenosine 3 mg/mL was stable in polypropylene syringes for 7 days at
      25 degrees C, 14 days at 5 degrees C, and 28 days at -15 degrees C; adenosine
      0.75 mg/ mL in 0.9% sodium chloride injection and in 5% dextrose injection was
      stable in polypropylene syringes and PVC bags for 16 days at 25, 5, and -15
      degrees C; and adenosine 0.75 mg/mL in lactated Ringer's injection and in 5%
      dextrose and lactated Ringer's injection was stable in syringes and bags for 14
      days at 25, 5, and -15 degrees C.

PMID- 9522933
TI  - ASHP advances Healthy People 2000 objectives.

PMID- 9522934
TI  - Selection of narcotic analgesics for pain associated with pancreatitis.

PMID- 9522935
TI  - Home care practice as a model for providing pharmaceutical care.

PMID- 9522936
TI  - Assay reliability.

PMID- 9522937
TI  - Effect of five percent dehydration on breath hydrogen concentrations in dogs.
AB  - OBJECTIVE: To determine the effect of mild dehydration (5%) on expired breath H2
      concentrations in dogs. ANIMALS: 10 healthy, colony-source dogs. PROCEDURE:
      Expired breath samples were collected at baseline, and every 90 minutes for 18
      hours after ingestion of a test meal (commercial dog food and kibbled wheat) in
      fully hydrated dogs and in the same dogs when they had lost 5% of their body
      weight after food and water deprivation. The areas under the breath H2
      concentration versus time curves (AUC) for the dehydrated and nondehydrated
      states were compared, using a two-stage, balanced, crossover, repeated measures
      technique. The number of breath samples considered to be contaminated by flatus
      were compared by use of a one-sided sign test. RESULTS: Expired breath H2
      concentration of dogs during the dehydration test period was significantly (P <
      0.02) greater than that during the nondehydration test period. In addition,
      flatulence was significantly (P < 0.033) more frequent in dogs during the
      dehydration period. CONCLUSIONS: Dehydrated dogs have greater expired breath H2
      concentration and produce more flatus after ingestion of a carbohydrate
      containing meal. Considered together, these findings suggest that dehydration
      results in an increase in the net amount of H2 produced in the gastrointestinal
      tract. CLINICAL RELEVANCE: Care should be taken to assess the hydration status,
      and to correct hydration deficits of dogs prior to breath H2 testing.

PMID- 9522938
TI  - Serum markers of bone metabolism in dogs.
AB  - OBJECTIVE: To establish reference values for a panel of serum markers of bone
      turnover in dogs of various ages. ANIMALS: Dogs in 4 age groups (0 to 1 year; 1
      to 2 years; 3 to 7 years; > 8 years). PROCEDURE: Serum concentrations of the
      carboxyterminal propeptide of type-I procollagen (PICP) and the aminoterminal
      propeptide of type-I procollagen (PINP), both markers of type-I collagen
      synthesis (hence, bone formation), were measured by use of commercial human
      radioimmunoassay kits. Serum concentrations of the carboxyterminal cross-linked
      telopeptide of type-I collagen (ICTP), a marker for type-I collagen breakdown
      (hence, bone resorption), also were measured by use of a commercial human
      radioimmunoassay kit. Serum osteocalcin (OC) concentrations and alkaline
      phosphatase (ALP) isoenzyme activities were measured by use of techniques
      developed specifically for dogs. RESULTS: As expected, the highest values for all
      of the markers were found in young dogs (< 12 months old). Concentrations of OC
      and ICTP decreased with age, and were lowest in dogs > 8 years old. Total ALP and
      bone-specific ALP activities initially decreased with age, then increased in dogs
      > 8 years old. CONCLUSIONS AND CLINICAL RELEVANCE: Serum markers of bone turnover
      may be useful diagnostic and prognostic tools for management of dogs with
      musculoskeletal disorders.

PMID- 9522939
TI  - Oral malodor measurements on a tooth surface of dogs with gingivitis.
AB  - OBJECTIVE: To measure production of volatile sulfur compounds (VSC) responsible
      for halitosis on the crown surface of the maxillary fourth premolar of dogs with
      gingivitis. ANIMALS: 28 dogs owned by veterinary students who complained that
      their dogs had halitosis. PROCEDURE: Clinical dental indices (plaque index,
      calculus index, and gingival index) were measured on the most diseased maxillary
      fourth premolar tooth. Production of VSC from the crown surface of the tooth was
      recorded by use of a portable sulfide monitor. Measurements were performed
      several times on each dog over a 2-month period, resulting in 98 series of
      measurements. RESULTS: Dogs with heavy amounts of plaque or calculus (plaque and
      calculus indices of 2 or 3) had significantly higher VSC readings than did dogs
      with no visible plaque and calculus accumulation. Significant (P = 0.0008)
      correlation was found between VSC measurements and plaque index, and significant
      correlations were found between VSC measurements and calculus index (P = 0.00118)
      and gingival index (P = 0.00475). CONCLUSION: VSC production recorded on the
      crown of maxillary fourth premolar teeth of dogs with gingivitis is significantly
      correlated with the amount of plaque and calculus accumulation and with severity
      of gingivitis. CLINICAL RELEVANCE: VSC measurements on tooth surfaces could be
      used as a site-specific method to assess, in conjunction with clinical dental
      variables, effectiveness of dental hygiene products.

PMID- 9522941
TI  - Immunocytochemical differences in adenohypophyseal cells among adult Mongolian
      pony mares, stallions, and geldings.
AB  - OBJECTIVE: To analyze the sex difference in 6 kinds of adenohypophyseal cells of
      Mongolian ponies and the effect of prepubertal orchidectomy on adenohypophyseal
      cells. SAMPLE POPULATION: Pituitary glands collected from 15 adult Mongolian
      ponies, 5 to 10 years old: 5 stallions, 5 mares, and 5 geldings, orchidectomized
      between the ages of 1 and 2 years. PROCEDURE: Morphologic comparison of 6 kinds
      of adenohypophyseal cells among mares, stallions, and geldings was done, using
      immunocytochemistry and morphometry. RESULTS: A sex difference was evident in the
      percentage of somatotrophs, gonadotrophs (follicle-stimulating hormone [FSH] and
      luteinizing hormone [LH] cells), and lactotrophs in adult ponies: somatotrophs
      were more numerous (P = 0.0003) in stallions (approx 40%) than in mares (approx
      25%), whereas FSH and LH cells and lactotrophs were more numerous (P = 0.0116, P
      = 0.0044, P = 0.0085, respectively) in mares (approx 10, 20, and 24%,
      respectively) than in stallions (approx 6, 15, and 15%, respectively).
      Prepubertal orchidectomy markedly reduced the proportion of somatotrophs (approx
      28%; P = 0.0016) and increased that of lactotrophs (approx 22%; P = 0.0318) in
      geldings, compared with stallions. The LH cell area was larger in mares than
      stallions (P < 0.0001). Prepubertal orchidectomy increased FSH (P = 0.0005) and
      LH (P < 0.0001) cell areas in adult geldings, compared with stallions.
      CONCLUSIONS: A sex difference exists in adenohypophyseal cells of adult ponies:
      somatotrophs are more abundant in stallions; FSH and LH cells and lactotrophs are
      more abundant in mares. Our data indicate that equine testes during postnatal
      life may stimulate development of GH cells while suppressing development of FSH
      and LH cells and lactotrophs. The effects of prepubertal orchidectomy on pony
      somatotrophs and lactotrophs differ greatly from effects on those cells in mice.

PMID- 9522940
TI  - Use of the urine cortisol-to-creatinine ratio for monitoring dogs with pituitary
      dependent hyperadrenocorticism during induction treatment with mitotane (o,p'
      DDD).
AB  - OBJECTIVE: To determine whether the urine cortisol-to-creatinine ratio (UCCR)
      could replace the ACTH stimulation test in monitoring effectiveness of mitotane
      induction treatment in dogs with pituitary-dependent hyperadrenocorticism (PDH).
      ANIMALS: 15 dogs with PDH. PROCEDURE: All 15 dogs were given an induction dose of
      mitotane (o,p'-DDD: 35 to 50 mg/kg of body weight/d) for 3 to 14 days. During the
      induction period, free-catch morning urine samples were collected for
      determination of UCCR, followed by ACTH stimulation testing, every other day.
      Treatment response was divided into 3 categories: well-controlled PDH (post-ACTH
      serum cortisol concentration > or = 28 nmol/L but < or = 138 nmol/L), deficient
      cortisol secretion (post-ACTH serum cortisol concentration < 28 nmol/L), and
      excess cortisol secretion (post-ACTH serum cortisol concentration > 138 nmol/L).
      RESULTS: The linear relation between UCCR and post-ACTH serum cortisol
      concentration was significant (P < 0.001); however, the prediction intervals
      surrounding the line were too broad to be clinically useful. The UCCR overlapped
      among the 3 categories of treatment response. Nevertheless, dogs with PDH
      receiving mitotane induction treatment and with UCCR > 79 x 10(-6) were always
      classified as having excess cortisol secretion. CONCLUSION AND CLINICAL
      RELEVANCE: The UCCR failed to predict post-ACTH cortisol concentration during
      mitotane induction treatment sufficiently close to be a clinically reliable
      indicator of treatment control. Seemingly, however, UCCR > 79 x 10(-6) obtained
      from a dog with PDH during mitotane induction would indicate inadequate adrenal
      cortex destruction and the need for continued mitotane induction; UCCR < or = 79
      x 10(-6) would be inconclusive.

PMID- 9522942
TI  - Genetic test for myophosphorylase deficiency in Charolais cattle.
AB  - OBJECTIVE: To develop a simple test for the determination of genetic
      susceptibility to myophosphorylase deficiency in Charolais cattle. ANIMALS: 48
      adult Charolais cattle and 233 calves from one herd and 3 Charolais cattle from 2
      other herds. Sixty Piedmontese and 34 Saler cattle provided negative-control
      samples. PROCEDURE: Cattle were from a Charolais herd in which myophosphorylase
      deficiency was identified and 2 other herds in which cattle had signs compatible
      with the disease. Genomic DNA was isolated from heparinized blood samples. A
      segment of the myophosphorylase gene containing the mutation site was amplified
      by polymerase chain reaction assays, and the genotype (normal vs affected allele)
      was determined by using restriction enzyme and agarose gel electrophoretic
      analysis. RESULTS: The 3 myophosphorylase genotypes (homozygous normal,
      homozygous affected, and heterozygous) could be readily identified. Segregation
      of the affected allele could be determined in an extended pedigree, and all
      clinically affected cattle were homozygous for this allele. Determination of the
      distribution of normal and affected alleles in a large population did not
      indicate a strong selective advantage for heterozygous carriers in this herd.
      Heterozygotes were also identified in Charolais cattle from the 2 other herds.
      CONCLUSIONS: Breeders of Charolais cattle can use this genetic test to perform
      marker-assisted selection and remove cattle with the mutant myophosphorylase
      allele from the breeding population. Alternatively, they could more accurately
      determine selective advantages and disadvantages for cattle with the affected
      allele. CLINICAL RELEVANCE: Development of this test enables rapid genetic
      screening of Charolais and related breeds of cattle for detection of the mutation
      responsible for myophosphorylase deficiency.

PMID- 9522943
TI  - Biochemical and ribotypic comparison of Actinomyces pyogenes and A pyogenes-like
      organisms from liver abscesses, ruminal wall, and ruminal contents of cattle.
AB  - OBJECTIVE: To isolate Actinomyces pyogenes and A pyogenes-like (APL) organisms
      from the ruminal wall and ruminal contents of cattle and compare them with
      isolates from liver abscesses from the same animals, using ribosomal DNA
      restriction fragment length polymorphism analysis or ribotyping. PROCEDURE:
      Specimens of liver abscesses, ruminal walls, and ruminal contents were collected
      from 59 cattle at slaughter. All beta-hemolytic, pinpoint colonies that were gram
      positive, pleomorphic rod-shaped, and catalase negative, and that hydrolyzed
      casein and gelatin were presumptively identified as A pyogenes and were
      characterized biochemically, using an identification kit. The isolates that
      resembled A pyogenes but fermented mannitol or raffinose, or both, were called
      APL organisms. Isolates from the ruminal wall and ruminal contents were compared
      with liver abscess isolates from the same animal by use of ribotyping. RESULTS:
      Actinomyces pyogenes and APL organisms were isolated more frequently from the
      ruminal wall than from ruminal contents. Ruminal isolates of A pyogenes and APL
      had biochemical characteristics similar to those of the isolates from liver
      abscesses. Among 6 sets of isolates (4 A pyogenes and 2 APL), 2 isolates from
      liver abscesses had ribopatterns identical to the corresponding ruminal wall
      isolates. Also, the APL organisms isolated from the ruminal content matched with
      the corresponding liver abscess isolates for both sets of specimens tested.
      CONCLUSIONS: The ruminal wall may be the niche for A pyogenes and APL organisms
      in the rumen. The genetic similarity, on the basis of ribotyping among isolates
      from liver abscesses, the ruminal wall, and ruminal contents of the same animal
      suggests that A pyogenes and APL organisms that cause liver abscesses originate
      from the rumen.

PMID- 9522944
TI  - Efficacy of an in-feed formulation of ivermectin against somatic larvae of
      Strongyloides ransomi in pregnant swine.
AB  - OBJECTIVE: To confirm that ivermectin fed for 7 days to pregnant sows controls
      transmission of Strongyloides ransomi larvae to pigs via the colostrum or milk.
      ANIMALS: 24 mixed-breed sows. PROCEDURE: The sows were infected with 250,000 S
      ransomi larvae on 3 occasions (days 63, 64, or 65, days 71 or 73, and days 78,
      79, or 80 of gestation). Eight sows received ivermectin at a dosage of 100
      micrograms of ivermectin/kg of body weight/d from days 92 to 99 of gestation, and
      8 sows were treated from days 103 to 110 of gestation; 8 remaining sows received
      unmedicated vehicle. Numbers of S ransomi larvae were counted in samples of
      colostrum or milk collected 1, 2, and 7 days after parturition. At 7 and 14 days
      after parturition, fecal samples were collected from each sow and from 4 pigs
      from each litter for determination of nematode egg counts; at the latter date,
      pigs were euthanatized and necropsied for worm counting. RESULTS: Pigs born to
      ivermectin-treated sows had significantly (P < 0.01) fewer adult S ransomi than
      did those born to control sows; efficacy was 100%. Treated sows had significantly
      (P < 0.05) fewer S ransomi larvae in colostrum/milk samples taken 1, 2, and 7
      days after parturition than did control sows; efficacy was 100%, with the
      exception of 1 S ransomi larva found in a milk sample from 1 treated sow at 2
      days after parturition. CONCLUSION AND CLINICAL RELEVANCE: Ivermectin fed to sows
      during the last third of gestation at a dosage of 100 micrograms/kg/d for 7
      consecutive days is highly efficacious for control of transmission of infective S
      ransomi larvae to pigs via colostrum or milk.

PMID- 9522945
TI  - Antipyrine pharmacokinetics and urinary excretion in female horses.
AB  - OBJECTIVE: To measure renal clearance of antipyrine and urinary excretion of
      antipyrine (AP) metabolites in horses by use of validated high-performance liquid
      chromatography (HPLC) methods. ANIMALS: 8 Standardbred mares. PROCEDURE: HPLC
      methods for measurement of AP in equine plasma and AP and its metabolites in
      equine urine were validated. Antipyrine (20 mg/kg of body weight) was
      administered i.v., and blood samples and urine specimens were collected over 24
      hours. RESULTS: Median plasma clearance of AP in horses was 6.2 ml/min/kg, of
      which < 2% could be attributed to renal clearance. Urinary excretion of AP and
      its metabolites over 24 hours accounted for < 22% of the AP dose administered.
      The major metabolite of AP in urine was 4-hydroxyantipyrine. CONCLUSIONS AND
      CLINICAL RELEVANCE: Use of the proven validated methods for measuring AP and its
      metabolites indicated that AP has minimal renal clearance in horses, suggesting
      that plasma clearance of AP reflects hepatic clearance. Combined with AP
      metabolite data, the pharmacokinetics of AP may be useful for assessment of
      hepatic cytochrome P450 activity in horses.

PMID- 9522946
TI  - Preclinical evaluation of a sterically stabilized liposome-encapsulated cisplatin
      in clinically normal cats.
AB  - OBJECTIVE: To evaluate the effects of administration of a sterically stabilized
      liposome-encapsulated cisplatin (SSL-CDDP) to cats. ANIMALS: 4 clinically normal
      cats. PROCEDURE: 2 of the cats were given multiple i.v. injections of SSL-CDDP at
      a dosage of 70 mg of free CDDP equivalent/m2 of body surface area at 3-week
      intervals. The other 2 cats received single i.v. injections of identical liposome
      preparations not containing CDDP. Vital signs; appetite; attitude; hematologic,
      serum biochemical, and urinalysis findings; and thoracic radiographic views were
      evaluated at predetermined intervals. RESULTS: Sterically stabilized liposome
      encapsulated cisplatin was well tolerated by all cats. The only significant
      alterations in measured variables were an increase in serum cholesterol
      concentration 2 days after injection, and repeatable pyrexia in the cats
      receiving SSL-CDDP that began 10 to 12 hours after injection and continued for 18
      hours, peaking at 40.5 to 41 C. Alterations in rectal temperature were not
      significant in cats receiving empty liposome vehicle. CONCLUSIONS: SSL-CDDP
      appears to be safe to administer to cats at a dosage of 70 mg of free CDDP
      equivalent/m2, a CDDP dose known to be therapeutic in dogs. Pyrexia, although
      marked, appears to be a short-term and well tolerated side effect. CLINICAL
      RELEVANCE: SSL-CDDP appears to abrogate the uniformly fatal side effects
      associated with administration of tumoricidal quantities of free CDDP to cats.
      This new formulation should allow investigation of the antitumor properties of
      CDDP against spontaneously arising neoplasms in cats.

PMID- 9522947
TI  - Pharmacokinetics of ketoprofen in healthy foals less than twenty-four hours old.
AB  - OBJECTIVE: To determine pharmacokinetic variables that describe disposition of
      ketoprofen after its i.v. administration to foals < 24 hours old. ANIMALS: 6
      healthy foals (1 male and 5 females); mean age, 12.5 (range, 8.5 to 17) hours at
      time of dose administration. PROCEDURE: Ketoprofen was administered i.v. to foals
      at a dosage of 2.2 mg/kg of body weight. Ketoprofen concentration in plasma
      samples was analyzed, using high-performance liquid chromatography. Concentration
      versus time profiles were analyzed according to standard pharmacokinetic
      techniques. Blood samples were obtained from foals by jugular venipuncture at
      defined times during a 48-hour period. Samples were centrifuged, and plasma was
      frozen at -70 C until analyzed. One-, two-, and three-compartment analyses were
      conducted. The most appropriate model was determined by use of Akaike's
      information criterion analysis. RESULTS: Plasma concentration versus time
      profiles were best described, using a two-compartment open model. Clearance
      (normalized for body weight) was significantly lower than that determined for
      adult horses. Volume of distribution (normalized for body weight) was larger than
      that determined for adult horses. Mean (harmonic) plasma half-life for healthy
      foals < 24 hours old was 4.3 hours. CLINICAL RELEVANCE: Although additional
      factors, such as dehydration or sepsis, must be considered on a case-by-case
      basis, the dose of ketoprofen administered to foals < 24 hours old should be
      different from the dose administered to adult horses. Under similar clinical
      circumstances, doses in foals should be increased by as much as 1.5 times to
      produce comparable therapeutic concentrations; longer dose intervals, based on
      clinical response, would be necessary to avoid drug toxicity.

PMID- 9522948
TI  - Effect of synovial membrane infection in vitro on equine synoviocytes and
      chondrocytes.
AB  - OBJECTIVE: To determine the functional response of synovium to infection, and the
      influence of infected synovium on articular cartilage metabolism. SAMPLE
      POPULATION: Synovium and articular cartilage explants from the midcarpal and
      tarsocrural joints of adult horses. PROCEDURE: For experiment 1, synovium
      explants were incubated as follows: control--incubation in standard medium,
      infected (I)--incubation with Staphylococcus aureus, and infected-filtered (IF)-
      incubation with medium collected from the infected group and filtered (0.22
      micron filter). Daily collected medium was assayed for interleukin 1 beta (IL-1
      beta), IL-6, tumor necrosis factor, and hyaluronan (HA) concentrations. For
      experiment 2, cartilage explants were incubated as follows: control--incubation
      in standard medium, and IF--incubation in medium collected from infected synovium
      cultures and filtered. After 48 hours, explant proteoglycan synthesis and
      endogenous proteoglycan and glycosaminoglycan contents were determined. RESULTS:
      IL-1 beta and IL-6 values were significantly increased in synovium explants from
      the I and IF groups. Hyaluronan concentration was lower in I and IF groups.
      Proteoglycan synthesis and content, and total glycosaminoglycan and chondroitin
      sulfate concentrations, were significantly decreased in cartilage from the IF
      group. CONCLUSIONS: Bacterial infection was associated with decreased HA
      concentration and increased mediator release. These effects were also observed
      despite elimination of bacteria. Exposure to sterile but previously infected
      medium decreased articular cartilage matrix synthesis and composition. CLINICAL
      RELEVANCE: Resident synovial cells may contribute appreciably to articular damage
      during bacterial infection in the absence of migrant inflammatory cells. This
      response is prolonged despite elimination of the bacteria.

PMID- 9522949
TI  - Study of spinal cord evoked injury potential by use of computer modeling and in
      dogs with naturally acquired thoracolumbar spinal cord compression.
AB  - OBJECTIVE: To add objective measurements of the characteristics of evoked injury
      potentials (EIP) and their relations to clinical severity in dogs with
      thoracolumbar spinal cord damage. ANIMALS: 25 dogs with naturally acquired spinal
      cord compression attributable to disk extrusion or vertebral fracture at the
      level of the thoracolumbar junction and with various degrees of
      paresis/paralysis. PROCEDURE: Spinal cord potentials evoked by tibial nerve
      stimulation were recorded every 5 to 10 mm at the lamina level in the vicinity of
      the cord compression. This allowed an EIP to be recorded even in the least
      handicapped dogs. A computer model yielded information about the waveform changes
      of the EIP in the vicinity of conduction blocks. RESULTS: The EIP waveform
      changed from biphasic to monophasic a short distance caudad to the location of
      spinal cord compression. Location of a maximal conduction block was measured in
      relation to position of the electrodes recording this waveform change. The
      distance between the assumed conduction block and the actual spinal cord
      compression was larger in the most affected dogs. The amplitude of the EIP was
      not related to severity of the clinical picture; however, the proximity of the
      recording electrode to the spine influenced the amplitude and the waveform of the
      EIP. CONCLUSION AND CLINICAL RELEVANCE: Change in the EIP waveform from biphasic
      to monophasic makes it possible to estimate the conduction block location along
      the spinal cord. A large distance between the assumed conduction block and site
      of actual cord compression could be an objective argument to confirm severity of
      a lesion.

PMID- 9522950
TI  - Influence of tidal volume and positive end-expiratory pressure on inspiratory gas
      distribution and gas exchange during mechanical ventilation in horses positioned
      in lateral recumbency.
AB  - OBJECTIVE: To study effects of intermittent positive-pressure ventilation (IPPV)
      with large tidal volumes and addition of positive end-expiratory pressure (PEEP)
      on maldistribution of ventilation in anesthetized horses positioned in lateral
      recumbency. ANIMALS: 6 healthy adult horses. PROCEDURE: Anesthesia was induced by
      i.v. infusion of thiopental sodium and guiafenesin and was maintained with
      supplemental doses of thiopental and i.v. infusion of chloral hydrate. Functional
      separation of the lungs was achieved, using a tube-in-tube intubation technique.
      Intermittent positive-pressure ventilation of both lungs with air was done by use
      of an anesthetic circle system and a ventilator. Data were collected during
      spontaneous respiration and during IPPV, using increasing tidal volumes with and
      without PEEP of 10 and 20 cm of H2O. RESULTS: Uneven distribution of inspired gas
      between the lungs that existed during spontaneous respiration was not altered by
      IPPV and large tidal volumes. Addition of PEEP caused a significant and
      reversible shift of inspired gas to the dependent lung and preferentially
      increased functional residual capacity of the nondependent lung. This was
      accompanied by significant increase in PaO2. With IPPV, the combined effects of
      PEEP and large tidal volume caused an increase of the fractional distribution of
      inspired gas to the dependent lung from 34% to 50%, accompanied by an increase in
      PaO2 and alveolar dead space of both lungs. CONCLUSIONS AND CLINICAL RELEVANCE:
      Use of PEEP during IPPV changes distribution of inspired gas. Increased in PaO2
      can be attributed to improved ventilation-perfusion, especially in the dependent
      lung, in which previously collapsed lung units might have been reopened and
      participated again in gas exchange after redistribution of inspired gas. The most
      pronounced effects of IPPV and PEEP were associated with high airway pressures,
      which are likely to offset the beneficial effects of the increase of PaO2 on
      total oxygen availability to the tissues because of the expected negative effects
      on cardiac output.

PMID- 9522951
TI  - Myoelectric activity of the ileum, cecum, and right ventral colon, and cecal
      emptying of radiolabeled markers in clinically normal ponies.
AB  - OBJECTIVES: To determine normal cecal emptying curves for liquid- and solid-phase
      radiolabeled markers and to further define myoelectric patterns of the ileum,
      cecum, and colon in healthy ponies. ANIMALS: 6 adult ponies. PROCEDURE: A cecal
      cannula and 12 bipolar Ag-AgCl recording electrodes were sutured to the ileum,
      cecum, and right ventral colon of the ponies. Radioisotopes, indium 111-labeled
      diethyltriaminepentaacetic acid (111In-DTPA) and technetium 99m (99mTc)-labeled
      sulfur colloid bound to egg albumen, were introduced through the cannula directly
      into the cecal body. Movement of these markers from the cecum was monitored by a
      gamma camera, and power exponential clearance curves were generated. Myoelectric
      data were collected before and after i.v. administration of isotonic saline (0.9%
      NaCl) solution, and were analyzed for spike burst (SB) rate, relative activity
      index, and mean burst duration. Myoelectric complexes were identified from
      observation of chart recordings or compressed, digitized data. RESULTS: Clearance
      curves were generated for liquid (111In-DTPA)- and solid (99mTc)-phase markers.
      Marker types were not different with respect to lag phase, but liquid markers
      emptied at a slightly faster rate than did solids. Baseline values were
      calculated after saline solution administration for each of the myoelectric
      variables investigated. A relation between ileal, cecal, and colonic myoelectric
      activity was identified. Activity consistent with the previously described
      colonic migrating myoelectric complex in the pelvic flexure was identified in the
      right ventral colon. CONCLUSIONS AND CLINICAL RELEVANCE: Baseline data on normal
      cecal emptying was obtained; this technique could be used to evaluate the effect
      of postulated motility-modifying treatments used in equine practice.

PMID- 9522952
TI  - Effect of alpha 2-adrenergic, cholinergic, and nonsteroidal anti-inflammatory
      drugs on myoelectric activity of ileum, cecum, and right ventral colon and on
      cecal emptying of radiolabeled markers in clinically normal ponies.
AB  - OBJECTIVE: To determine effect of xylazine hydrochloride (XYL), yohimbine
      hydrochloride (YOH), bethanechol chloride (BET), neostigmine methyl sulfate
      (NEO), or flunixin meglumine (FLU) on ileocecocolic myoelectric activity and
      passage of radiolabeled markers from the cecum. ANIMALS: 6 healthy adult ponies.
      PROCEDURE: A cecal cannula was surgically implanted, and 12 were sutured to the
      ileum, cecum, and right ventral colon. After a 12-hour nonfeeding period, 370 MBq
      of technetium 99m-labeled sulfur colloid in egg albumen and 37 MBq of indium 111
      labeled diethyltriaminepentaacetic acid in 60 ml of water were injected into the
      cecal apex. All drugs were administered i.v. as a bolus, with the exception of
      NEO, which was given SC: XYL, 0.5 mg/kg of body weight; YOH, 0.075 mg/kg; BET,
      0.025 mg/kg; NEO, 0.025 mg/kg; FLU, 1.1 mg/kg; and saline solution (SAL), 10 ml.
      Drugs were administered in a randomized complete block design, each treatment was
      administered twice to each pony, and dual-phase scintigraphic images were
      obtained. The time to 50% emptying (t50) and the slope of the emptying curve
      (beta) were derived from the calculated power exponential equation. RESULTS: The
      t50 after BET (184.8 +/- 16.5 minutes) and NEO (124.7 +/- 16.5 minutes)
      administration were significantly shorter than values after saline (230.2 +/-
      17.1 minutes) administration. The t50 after XYL administration (250.5 +/- 18.6
      minutes) was longer, and that after YOH administration (190.1 +/- 16.2 minutes)
      was shorter, than the t50 after saline administration, but neither difference was
      significant. The t50 and beta after FLU administration differed from those after
      saline administration. Myoelectric data appeared to be well correlated with drug
      induced alterations in isotope clearance. CONCLUSIONS AND CLINICAL RELEVANCE:
      Cholinergic agonists, BET and NEO, have significant effects on the myoelectric
      activity of ileum, cecum, and right ventral colon, with the net effect of
      hastening cecal emptying.

PMID- 9522954
TI  - Effect of alpha-chymotrypsin on breaking strength and ultrastructural morphology
      of canine ciliary zonules.
AB  - OBJECTIVE: To determine the effect of alpha-chymotrypsin treatment on breaking
      strength and ultrastructural morphology of canine ciliary zonules. SAMPLE
      POPULATION: Eyes from young random-source dogs from an animal shelter. PROCEDURE:
      Eyes were obtained immediately after euthanasia of dogs. The enzyme alpha
      chymotrypsin was applied to the ciliary zonules of 1 eye of each dog; the other
      eye was treated with saline solution as a control. The breaking strength of
      ciliary zonules was measured, using a linear actuator and force transducer. The
      lenses and ciliary bodies were then analyzed by scanning and transmission
      electron microscopy. RESULTS: alpha-Chymotrypsin reduced the breaking strength of
      ciliary zonules by a mean +/- SD 44 (+/- 20)%, compared with that for saline
      treated control eyes. Increasing the volume of enzyme further decreased the
      breaking strength of the zonules. Differences in the appearance of the ciliary
      body by electron microscopy were not apparent between enzyme- and saline-treated
      specimens. CONCLUSIONS AND CLINICAL RELEVANCE: Application of alpha-chymotrypsin
      to enucleated canine eyes at a concentration used in people significantly reduces
      the breaking strength of canine ciliary zonules without any apparent damage to
      the ciliary body. alpha-Chymotrypsin may be useful in the removal of subluxated
      canine lenses and in removal of cataractous lenses in young dogs, in which
      phacoemulsification often results in appreciable post operative capsular
      opacification.

PMID- 9522953
TI  - Effect of erythromycin lactobionate on myoelectric activity of ileum, cecum, and
      right ventral colon, and cecal emptying of radiolabeled markers in clinically
      normal ponies.
AB  - OBJECTIVE: To determine the effect of erythromycin lactobionate (ERY) on
      ileocecocolic myoelectric activity and passage of radiolabeled markers from the
      cecum. ANIMALS: 6 healthy adult ponies. PROCEDURE: After a 12-hour nonfeeding
      period, 370 MBq of technetium 99m-labeled sulfur colloid in egg albumen and 37
      MBq of indium 111-labeled diethyltriaminepentaacetic acid in 60 ml of water were
      administered directly into the cecal apex. The following drug concentrations were
      tested: ERY, 0.01, 0.10, 1.0, and 10.0 mg/kg of body weight; ERY, 0.10 mg/kg
      bolus; and saline (0.9% NaCl) solution, 10 ml. All treatments, with the exception
      of the 0.10-mg/kg bolus and saline solution, were infusions administered i.v.
      during a 60-minute period in a randomized complete block design. Each treatment
      was administered 2 times/pony. Dual-phase scintigraphic images were obtained, and
      the best-fit function was determined for each study, using data from the right
      side. Myoelectric data were collected before and after each treatment and
      analyzed for spike burst rate, relative activity, and burst duration. RESULTS:
      The time to 50% emptying (t50) after ERY administration was dose dependent, and
      all treatments, with the exception of the 0.01-mg/kg infusion, resulted in a
      significantly shorter t50 than that observed after saline administration (230.2
      +/- 17.12 minutes). The shortest t50 was observed after the 1.0 mg/kg dosage of
      ERY (76.9 +/- 22.0 minutes). Although not significantly different, the t50 and
      beta were shorter (108.6 +/- 25.9 minutes) and steeper after a bolus dose of 0.10
      mg/kg of ERY than after infusion at the same dosage (131.1 +/- 18.7 minutes).
      CONCLUSIONS AND CLINICAL RELEVANCE: ERY may be a useful prokinetic for prevention
      or treatment of cecal motility dysfunction. The ability of ERY to evoke a similar
      response during the early postanesthetic or postoperative period remains to be
      determined.

PMID- 9522955
TI  - Effect of ischemia and reperfusion on oxidative processes in the large colon and
      jejunum of horses.
AB  - OBJECTIVE: To evaluate and compare oxidative processes during ischemia and
      reperfusion of the equine large colon and jejunum. ANIMALS: 2 groups of 6
      anesthetized horses undergoing a terminal procedure. PROCEDURE: Isolated loops of
      large colon and jejunum were subjected to 2 hours of ischemia, followed by 2
      hours of reperfusion. Tissue specimens were taken after 105 minutes of ischemia
      and 10, 30, 60, and 120 minutes of reperfusion. Mesenteric arterial and venous
      blood samples were collected for blood gas analysis at the same times to evaluate
      ischemia and reoxygenation. Oxidative processes in tissues were evaluated by use
      of biochemical assays for malondialdehyde and conjugated dienes and by use of the
      manganese-diaminobenzidine histochemical technique for localized superoxide
      generation. RESULTS: Significant quantities of malondialdehyde and conjugated
      dienes were detected in the jejunum after 60 and 120 minutes of reperfusion
      together with histochemical evidence of superoxide generation in jejunal
      endothelial cells and in submucosal neutrophils and eosinophils. CONCLUSIONS:
      Oxidative processes do not appear to have an appreciable role in inducing damage
      in the equine large colon during reperfusion after 2 hours of ischemia. In
      contrast to the jejunum, reactive oxygen species are not generated in measurable
      quantities in the large colon subsequent to ischemia and reperfusion. CLINICAL
      RELEVANCE: Free radical scavengers are not likely to be effective in prevention
      of equine colonic mucosal deterioration after ischemia.

PMID- 9522956
TI  - Long-term consequences of experimental desmotomy of the accessory ligament of the
      deep digital flexor tendon in adult horses.
AB  - OBJECTIVE: To evaluate clinical and biomechanical consequences of desmotomy of
      the accessory ligament (AL) of the deep digital flexor tendon (DDFT) of equine
      forelimbs and determine whether this procedure is a viable treatment for chronic
      desmitis of the AL-DDFT. ANIMALS: 6 adult Standardbred trotters. PROCEDURE:
      Biomechanical recordings obtained before and 6 months after desmotomy were
      compared. Walk and trot joint angles, ground reaction forces, peak joint moments,
      and tendon forces were assessed. RESULTS: Within 10 days after surgery, all
      horses were sound at a trot. Swelling, increased carpal flexion in the terminal
      stance phase, and incidental stumbling at the beginning of exercise were
      observed. Flexion angle in the carpal joints was significantly increased at the
      end of the stance phase. Peak moments around the distal interphalangeal joint and
      forces in the DDFT and AL-DDFT were decreased. Metacarpophalangeal joint angles,
      peak metacarpophalangeal joint moments, and peak loading of the suspensory
      ligament and the superficial digital flexor tendon were unchanged. CONCLUSION: 6
      months after desmotomy, AL-DDFT strain was reduced without causing changes in
      joint angles or increasing tendon loads or joint moments that could be considered
      hazardous for the horses. CLINICAL RELEVANCE: Changes in locomotion that remained
      6 months after AL-DDFT desmotomy would be acceptable for horses with chronic
      desmitis if conservative treatment failed.

PMID- 9522957
TI  - Effects of experimental desmotomy on material properties and histomorphologic and
      ultrasonographic features of the accessory ligament of the deep digital flexor
      tendon in clinically normal horses.
AB  - OBJECTIVE: To evaluate posttrauma biomechanical behavior of the scar attributable
      to desmotomy of the accessory ligament of the deep digital flexor tendon (AL
      DDFT), compared with the histomorphologic and ultrasonographic appearance.
      ANIMALS: 5 Standardbred trotters. PROCEDURE: Gross appearance, length, cross
      sectional area (CSA), in vitro material properties, and ultrasonographic and
      histomorphologic features were studied 6 months after desmotomy. Tensile tests
      were conducted, with forces and elongation simultaneously recorded. Surgically
      treated limbs were compared with nontreated contralateral limbs. RESULTS: The CSA
      of the treated ligaments was increased threefold, and treated ligaments were 1 cm
      longer than control ligaments. In the healed AL-DDFT, stress and material
      stiffness were approximately a third of those values for controls. The functional
      characteristics, force and elongation at failure, reached 80% of control values.
      Ultrasonographic and the histomorphologic examination of the scar tissue revealed
      high amounts of randomly oriented collagen. CONCLUSION: From the ultrasonographic
      and histomorphologic findings and the material properties, it was concluded that
      the scar tissue was of inferior quality. However, the functional properties had
      been restored for the most part by increase of the CSA. The length increase may
      lead to strain relief in the AL-DDFT after desmotomy. CLINICAL RELEVANCE:
      Desmotomy is recommended as treatment for chronic desmitis.

PMID- 9522958
TI  - Production and characterization of canine osteosarcoma cell lines that induce
      transplantable tumors in nude mice.
AB  - OBJECTIVE: To produce and characterize cell lines from canine primary
      appendicular osteosarcomas that induce transplantable tumors in athymic nude
      mice. ANIMALS: 57 six- to 8-week-old female athymic nude mice. PROCEDURE: Canine
      primary appendicular osteosarcoma tumors were harvested and cell lines were
      produced. Canine osteosarcoma (COSCA)-Toby (COSCA-T; 10 mice), COSCA-Princess
      (COSCA-Pr; 16) or canine osteosarcoma D-17 (ATCC CCL-183; 31) cells were injected
      into the proximal portion of the left tibia of nude mice to evaluate tumor
      production from each cell line; the right tibia served as the control. Tibial
      measurements were taken on alternating days to evaluate tumor growth during a 6
      month period. Student's t-tests were used to determine whether size of the
      proximal portion of the left and right tibias differed significantly during the
      observation period. RESULTS: 88% of mice receiving COSCA-Pr and 50% of mice
      receiving COSCA-T cells developed a tumor at the injection site by 9 days after
      implantation. The D-17 cells induced tumors in 50% of injected tibias; however,
      tumors were not detected for 79 days. Tumors generated from COSCA-Pr and COSCA-T
      cells in nude mice were histologically similar to the canine tumor from which
      they were developed. CONCLUSION: New osteosarcoma cell lines that can reliably
      and rapidly induce transplantable tumors in nude mice were developed. CLINICAL
      RELEVANCE: Use of cell lines will allow evaluation of new treatments of canine
      primary appendicular osteosarcoma in a nude mouse model.

PMID- 9522959
TI  - Expression of c-kit and stem cell factor mRNA in liver specimens from healthy
      adult dogs.
AB  - OBJECTIVE: To determine expression of c-kit and stem cell factor (SCF) mRNA in
      liver specimens from healthy adult dogs and to investigate whether
      differentiation of mast cells in the liver of dogs is supported by the c-kit
      receptor tyrosine kinase/SCF system. ANIMALS: 3 healthy adult Beagles. PROCEDURE:
      The nucleic acid sequence of the canine c-kit fragment of the intracellular
      tyrosine kinase domain was determined. Magnitudes of c-kit and SCF mRNA
      expression in liver samples was determined by means of northern blot analysis,
      using probes based on canine sequences. To determine which cells were expressing
      c-kit and SCF mRNA, in situ hybridization was performed. RESULTS: Expression of c
      kit and SCF mRNA in liver samples was weak but appreciable. In situ hybridization
      revealed that c-kit and SCF mRNA expression was restricted to mast cells and
      plasma cells, respectively. CONCLUSION: Expression of SCF mRNA was detected in
      liver from healthy adult dogs. The c-kit receptor tyrosine kinase/SCF system may,
      possibly in combination with other growth factor and receptor systems, be
      involved in proliferation and differentiation of liver mast cells in dogs.

PMID- 9522960
TI  - Postprandial dyslipidemia: a risk factor for coronary heart disease.

PMID- 9522961
TI  - Gestational age and origin of human milk influence total lipid and fatty acid
      contents.
AB  - The human milk composition may be influenced by several factors, such as
      gestational age or genetic characteristics and dietary habits of different
      populations. To analyze the total lipid and fatty acid contents of human milk, we
      have conducted two studies, one on mothers who had delivered preterm and term
      newborns and another on mothers from two different sociocultural backgrounds
      (Spain and Panama). The total lipid content (g/100 g wet weight) was
      significantly higher in term (2.76 +/- 0.66; mean +/- SD) than in preterm mature
      milk (1.06 +/- 0.4). The relative amount of 18:1n-9 was significantly higher in
      preterm than in term milk for transitional and mature milk, whereas that for the
      colostrum followed the opposite trend. Concerning the comparison between milk
      from mothers born in different countries, the relative contents of each of the
      fatty acids 16:0, 16:1n-7, 18:2n-6, 18:3n-3, and 22:5n-3 were higher in
      Panamanian than in Spanish milk, whereas the mean percentages of saturated fatty
      acids < 14:0, of 16:1n-9, and of 18:1n-9 were higher in Spanish than in
      Panamanian milk. Statistically significant differences were found during the
      three periods of lactation considered for almost all the fatty acids mentioned
      above, especially for 18:1n-9 and 18:3n-3. Although the potential biological
      significance of the changes in oleic acid content between preterm and term milk
      remains unclear, differences in fatty acid content between Spanish and Panamanian
      milk reflect the different composition of the diet among women from these
      countries.

PMID- 9522962
TI  - Qualitative analysis of human milk produced by women consuming a maize
      predominant diet typical of rural Mexico.
AB  - The milk composition of women on a typical rural Mexican diet was compared with
      that secreted by American women, consuming a diet typical of affluent countries.
      Milk concentrations of free fatty acids, cholesterol, total amino acids, and
      selected key minerals were analyzed at 4 or 6 months postpartum. The total milk
      fat concentration was lower in the Otomi (22.7 +/- 6.7 mg/g milk) than in the
      American women (31.3 +/- 5.4 mg/g milk, p = 0.001). Although the absolute
      concentration did not differ, cholesterol, expressed in terms of total lipid, was
      higher in the Otomi milk (3.9 +/- 1.1 vs. 3.1 +/- 0.7 mg/g fat, p = 0.005).
      Saturated medium-chain (C10:0-C14:0) and unsaturated intermediate-chain fatty
      acids (C16:1 and C18:2) were higher in the Otomi than in the American milk (p <
      0.03). The concentrations of C16:0, C18:0, and C18:1 were significantly lower in
      Otomi than in American milk. The milk concentrations of protein and nonprotein
      nitrogen were comparable between the two groups. The concentrations of serine,
      proline, cystine, methionine, and tryptophan were higher in the Otomi than in the
      American milk (p < 0.05-0.001). The concentrations of valine and isoleucine were
      significantly lower in the Otomi milk (p = 0.05). Expressed per gram of milk
      protein, the cystine, methionine, lysine, and tryptophan concentrations were
      higher, and the glutamine/glutamate, valine, isoleucine, and arginine levels were
      lower in the Otomi milk. The concentrations of phosphorus and copper were lower
      in the Otomi than in the American milk at 4 months postpartum (p = 0.05). These
      differences in milk fatty acid and amino acid patterns and mineral content are
      unlikely to affect infant growth, but may have other biological consequences yet
      to be ascertained.

PMID- 9522963
TI  - Iron status in a healthy population of Hungarian secondary school boys and girls.
AB  - Iron status was assessed in a sample of 103 male and 282 female students aged
      from 15 to 18 years attending secondary schools in Budapest. Using a ferritin
      model, in boys the prevalence of iron depletion, iron-deficient erythropoiesis
      and iron-deficient anemia was 3.9, 2.9 and 1.0%, respectively. In girls these
      values were 9.6, 8.2 and 2.8%, respectively. Males had better eating habits than
      females. Data for nutrients intake connected with iron status are discussed. The
      authors recommend the improvement of iron status by dietary means and oppose the
      indiscriminate iron supplementation.

PMID- 9522964
TI  - Could long-term alimentary iron overload have an impact on the parameters of
      oxidative stress? A study on the basis of a village in southern Estonia.
AB  - The effects of long-term alimentary (drinking water) iron overload on the
      parameters of oxidative stress were evaluated. The study group (n = 35) from a
      village in southern Estonia was 37.1 +/- 13.3 years old, and the mean period of
      drinking water iron overload was 20.6 +/- 9.3 years. The serum iron content was
      significantly higher than normal. The total iron-binding capacity of serum tended
      to be lowered. There was no change in the transferrin content. The parameters of
      lipid peroxidation like conjugated dienes and thiobarbituric acid reactive
      substances showed also significant differences. In addition, the red blood cell
      glutathione content was also decreased. The total antioxidant capacity of serum
      was not changed. It can be concluded from our results that a long-term alimentary
      iron overload results in a positive serum iron balance, which, in turn, yields an
      increased oxidative stress.

PMID- 9522965
TI  - Physiological effects of a pea protein isolate in gnotobiotic rats: comparison
      with a soybean isolate and meat.
AB  - Pea proteins have been considered for the introduction into the human diet only
      recently. This protein source was tested on nutritional and digestive parameters
      in heteroxenic male Fischer rats inoculated with a human faecal microflora from a
      methane producer. Compared to soybean proteins, pea proteins have similar effects
      on the rat's endogenous and bacterial digestive patterns. Compared to the pea
      proteins, a diet containing a standard meat meal enhanced the pH and the
      production of ammonia, while a lyophilized beef meat enhanced that of urea. The
      diet containing the standard meat decreases short-chain fatty acids and modifies
      the ratio of caecal short-chain fatty acids. Both animal diets decreased the
      specific activities of pancreatic proteases such as chymotrypsin (EC 3.4.21.1),
      trypsin (EC 3.4.21.4), and carboxypeptidase A (EC 3.4.17.1) when compared to the
      diet containing the pea isolate. In conclusion, the whole composition of the
      diet, more than the origin of the dietary protein, influences the rat's digestive
      pattern.

PMID- 9522967
TI  - Ageing gracefully in 2020.

PMID- 9522966
TI  - Triglyceride turnover, lipoprotein lipase activity, and fat cell size in adipose
      tissue of rats during the first 2 weeks of pregnancy.
AB  - Understanding the biological function of the fat retained during pregnancy is
      important when estimating energy needs during reproduction. Women as well as rats
      are often considered to gain fat at specific anatomical sites during pregnancy
      and use this fat as a source of energy during lactation. However, mobilized body
      fat covers only a minor part of the energy needed by the lactating rat dam. In
      this paper, fat cell size, lipoprotein lipase activity, as well as triglyceride
      turnover in parametrial and subcutaneous adipose tissues were studied during the
      first 2 weeks of gestation and in virginal controls to further explore the
      metabolic and physiological basis for changes in body fat during reproduction in
      rats. Pregnancy increased the size of parametrial but not of subcutaneous
      adipocytes. The lipoprotein lipase activity in subcutaneous adipocytes was not
      increased by pregnancy. The accumulation in adipose tissue of 14C from orally
      administered 14C-oleic acid was higher in virginal than in pregnant rats. No
      effect of pregnancy on the rate of lipid turnover in parametrial or subcutaneous
      adipocytes was found. The findings are in accordance with the contention that
      body fat gained during rat pregnancy, to a large extent, is a consequence of a
      general growth of maternal tissues rather than the result of a stimulating effect
      of pregnancy on fat accumulation by adipocytes from specific body sites.

PMID- 9522968
TI  - Functional status of the elderly in Singapore--the trend over a decade.
AB  - The study looks at the level and types of functional disabilities of a random
      sample of elderly individuals in the community through direct interviews using a
      questionnaire in 1992 and compares the results to that obtained from a similar
      study done in 1982. Two hundred and eighty-three elderly aged 60 years and above
      were studied. In the activities of daily living (ADL) functions category, most
      elderly individuals were independent in dressing (96.1%), bathing (95.4%),
      preparing meals (92.6%) and using the toilet (89.4%). There was increasing
      disabilities in the instrumental activities of daily living (IADL) functions, in
      ascending order of difficulty--light chores (81.3% independent), shopping (67.8%
      independent) and heavy chores (60.1% independent). Eight (2.8%) of the elderly
      were confined to bed most of the time. Comparing the results with the 1982
      cohort, the 1992 cohort was more dependent, with significant increase in
      difficulty with dressing, using the toilet, bathing, and higher functional
      activities. There was also significant increase in the number of elderly confined
      to bed most of the time, from 1% to 2.8%. The only activity that showed a reverse
      trend was food preparation. The trend of dependence among the elderly is growing
      and deserves further specific studies to examine the possible reasons for the
      increasing disabilities in the elderly population, especially as the population
      is ageing rapidly.

PMID- 9522970
TI  - Postural stability in non-insulin dependent diabetics.
AB  - Postural stability in 55 non-insulin dependent diabetics was compared with 53 non
      diabetic controls matched for age and gender. The study was conducted in a
      primary care clinic, using a computerised postural sway system. Changes in the
      centre of pressure while the subjects stood on a force platform were recorded,
      and sway parameters computed using customised software. Clinical data were
      obtained by interview, physical examination, and from case records. Results of
      the study showed that non-insulin dependent diabetics were more unstable than the
      non-diabetic controls for four out of the six parameters studied (namely L,
      length of sway path; Vel, average speed of centre of pressure along its path; Ao,
      area included within the path of the centre of pressure; and Ae, 95% confidence
      elliptical area), after adjusting for height, weight, adequate sleep and alcohol
      intake the night before, and history of bone or thyroid disorders. Amongst
      diabetic subjects, significant factors associated with postural stability were
      age, weight, presence of peripheral neuropathy or cataract, metformin, use, and
      HbAlc levels > 9%. Further studies are indicated to look into factors affecting
      postural stability (other than diabetic neuropathy) in greater depth.

PMID- 9522969
TI  - The demography, clinical manifestations and natural history of human
      immunodeficiency virus (HIV) infection in an older population in Singapore.
AB  - In this retrospective study, we report 43 cases (41 males and 2 females) of human
      immunodeficiency virus (HIV) infection in the Singapore population aged 50 years
      and above at first presentation. We found an increasing proportion of these older
      individuals among our HIV-seropositive patients; from 4.8% in 1991 to 16.7% by
      mid-1996. The mean age at presentation was 59.2 years (range 50 to 75 years).
      They were mainly heterosexuals (93%) and the majority (79.1%) were previously or
      currently married. Thirty-six (83.7%) patients had multiple sexual exposures to
      commercial sex workers. Nearly all had acquired the infection through the sexual
      route. The majority (76.7%) were symptomatic at presentation. Common clinical
      presentations were weight loss (72%), respiratory symptoms (60%) and oral
      candidiasis (56%). More than half (58.1%) of the patients had acquired
      immunodeficiency virus (AIDS) at the time of first presentation with a low median
      CD4 count of 17 cells/mm3. Pneumocystis carinii pneumonia and tuberculosis were
      the common AIDS-defining diseases. Survival in patients presenting with AIDS
      (median survival 3 months) is poorer compared to younger HIV-seropositive
      patients (< 50 years; median survival 1 year). No increase in age-related
      infection or malignancy was seen. Common causes of death were pneumonia and
      septicaemia. Physicians should consider HIV infection in older patients
      particularly when he/she presents with unexplained weight loss, respiratory
      symptoms and oral candidiasis. A history of high-risk sexual behaviour must be
      sought in all patients, including the elderly.

PMID- 9522972
TI  - Ultrasound of the tibia--precision error, left versus right sides and correlation
      with bone mineral density.
AB  - Ultrasound of the tibia measures the speed of sound through cortical bone and is
      a measure of bone density and strength. Ten subjects were measured twice each on
      the same side by a single operator using the Myriad Soundscan 2000. Intra
      operator precision error expressed as CV% was 0.3%. Inter-operator precision
      error was also found to be 0.3% when results on the same ten subjects by two
      operators were analysed. Seventy-four subjects had their speed of sound (SOS)
      measured on both the left and right tibiae by a single operator. The Pearson
      correlation co-efficient was 0.83. Fifty subjects had their SOS measured as well
      as their bone mineral density (BMD) determined by dual energy X-ray
      absorptiometry (DEXA) using the Hologic QDR 2000. BMD measurements were made at
      the lumbar spine AP view, neck of femur, trochanter, Ward's triangle and total
      hip. Pearson correlations between these various sites and SOS were as follows:
      SOS versus BMD AP spine r = 0.61, P < 0.0001; SOS versus neck of femur r = 0.68,
      P < 0.0001; SOS versus trochanter r = 0.71, P < 0.0001; SOS versus Ward's
      triangle r = 0.7, P < 0.0001; SOS versus total hip r = 0.67, P < 0.0001. In
      conclusion, ultrasound of the tibia is a precise and promising tool in the
      assessment of osteoporosis. Further studies are needed to document its clinical
      usefulness.

PMID- 9522971
TI  - Out-patient management of febrile neutropenia in indigent paediatric patients.
AB  - Affordability of costly in-patient medical care and accessibility to the few
      cancer centres are serious problems faced by cancer patients in developing
      countries. Febrile neutropenia in particular is a major problem because delay in
      institution of antibiotic therapy can be rapidly fatal. We conducted a
      prospective non-randomised trial to evaluate the efficacy of administration of
      oral ofloxacin by caregivers to paediatric cancer patients with fever and
      neutropenia. Patients receiving chemotherapy who resided for away and were unable
      to reach the oncology ward within 12 hours of onset of fever or were unable to
      afford the expensive in-patient care were eligible for inclusion in the study.
      Requirements for enrollment included an absolute neutrophil count of < or = 0.5 x
      10(9)/L, a temperature of > or = 38 degrees C, and ability to take oral
      medications. Caregivers were instructed to immediately administer oral ofloxacin
      on recognition of fever and to maintain constant contact with the oncology staff.
      Eighty-five of the 91 episodes were evaluable. These were most patients with
      solid tumours or non-Hodgkin's lymphoma (79%). Duration of neutropenia and fever
      was short and majority had pyrexia of undetermined origin (84%). Seventy-seven
      (91%) of the febrile episodes responded to ofloxacin with resolution of fever and
      neutropenia and hospitalisation was never required. Eight (9%) patients required
      hospitalisation. Most of them had prolonged neutropenia. They all responded to
      parenteral antibiotic therapy. No toxicity was observed and the cost of therapy
      was negligible. Out-patient therapy with oral ofloxacin may be an alternative to
      hospitalisation for those paediatric patients who are unable to afford or do not
      have access to in-patient care.

PMID- 9522973
TI  - Correlation between oestrogen receptor protein expression in infiltrating ductal
      carcinoma of the breast by immunohistochemistry and cytosol measurements.
AB  - Fresh frozen neoplastic tissues from 70 infiltrating ductal breast carcinomas
      were analysed for cytosolic oestrogen receptor (ER) protein content using a solid
      phase enzyme immunoassay (EIA) method based on a "sandwich" principle (Abbott ER
      EIA monoclonal). Formalin-fixed, paraffin-embedded sections from the same
      carcinomas were examined for nuclear immunoreactivity against a monoclonal
      antibody for ER protein (Dako) using the standard avidin-biotin complex
      immunoperoxidase (IP) method after microwave antigen retrieval. The degree of ER
      positivity by IP was also scored according to a visual estimation of the
      percentage of cells expressing immunopositivity and the intensity of staining.
      Twenty-eight (40%) of the carcinomas were ER-positive by EIA and 34 (48.6%) were
      positive by IP. Twenty-five (35.7%) were ER-positive and 33 (47.1%) were ER
      negative by both methods. Nine (12.9%) were ER-negative by EIA but were positive
      by IP, this discrepancy being ascribed to sampling inadequacy for EIA. However, 3
      (4.3%) tumours were ER-positive by EIA and negative by IP. This discrepancy may
      be variously due to inadequate antigen retrieval, faulty technique and the
      possibility that the two methods do not measure identical ER proteins. IP appears
      to have an advantage over EIA in that it has a higher pick-up rate, does not
      require fresh tissue and can be applied to archival material. However, to reduce
      false negative estimations, it may be necessary to run IP staining using more
      than one ER antibody. Standardisation of the IP method for ER is desirable before
      this method is to be widely adopted in Malaysian laboratories. Quantitation of ER
      positivity by IP scoring correlated poorly with actual cytosolic levels. Caution
      should be exercised in attaching patient management value to visual IP scoring.

PMID- 9522974
TI  - The subcellular localisation and the time course of bismuth in the gastric mucosa
      of rats after short-term administration of colloidal bismuth subcitrate.
AB  - The aim of this study was to investigate if colloidal bismuth subcitrate (CBS)
      can penetrate the gastric mucus barrier to reach the different sites of the
      antral mucosa and to estimate the time course for CBS to reach and remain in the
      mucosa. A single dose of CBS was administered orally to rats that were sacrificed
      at different time intervals post treatment. The control group received gum acacia
      without CBS. Colloidal bismuth subcitrate, visualised as electron dense
      precipitate (EDP), was seen in the gastric mucus layer, intercellular spaces and
      intracellularly after 30 minutes and disappeared after 6 hours. Scant amounts of
      EDP were observed in the gastric crypts, confined only to the upper parts of
      these structures. We concluded that CBS can penetrate the mucus and has a wide
      but uneven distribution in the gastric mucosa. Colloidal bismuth subcitrate, in
      the concentration given only penetrated the upper two-thirds of gastric pits and
      not the lower one-third. We also concluded that CBS has to be given 6 hourly to
      ensure its continuous presence in the gastric mucosa.

PMID- 9522975
TI  - Gastrointestinal lymphoma--a review of 54 patients in Singapore.
AB  - Primary gastrointestinal (GI) lymphoma accounts for 2% to 5% of all GI
      malignancies. Primary therapy in uncomplicated GI lymphoma remains controversial.
      Fifty-four patients (male to female ratio of 4:3, median age 56 years) with GI
      lymphoma were studied to evaluate complications and results of therapy. The sites
      involved were the stomach (31), small bowel (12), large bowel (4), gallbladder
      (1) and multifocal (6). Distribution by stage and grade (Working Formulation or
      Kiel) were: IE-30%, IIE-43%, IIIE-6%, IV-20% and unknown-1%; low grade-33%,
      intermediate grade-59% and high grade-8%. Majority (54%) had diffuse large cell
      lymphoma. Twenty-three patients (43%) underwent primary resection of the tumour
      followed by chemotherapy in 14 or radiotherapy in 3. Seventeen patients (31%) had
      primary chemotherapy and 3 (6%) had primary radiotherapy. Of the 48 patients who
      underwent therapy, 52% had complete response. At the last follow-up (median 21
      months), 25 patients were disease-free. Overall survival was 67% at two years.
      Treatment strategies employing surgery, radiotherapy and chemotherapy, alone or
      in combination, do not appear to influence outcome. Surgical resection plus
      chemotherapy appear to be effective in the control of local and distant disease.

PMID- 9522976
TI  - Aldosterone to renin ratios in the evaluation of primary aldosteronism.
AB  - Primary aldosteronism, though an uncommon cause of hypertension, causes
      significant morbidity, making it important to diagnose and treat this condition.
      Its evaluation requires complex and time consuming investigative procedures in
      order to confirm the diagnosis and to differentiate between the subtypes of
      aldosterone producing adenoma and idiopathic hyperaldosteronism. Often, the
      values of renin and aldosterone are equivocal, and the diagnosis of primary
      aldosteronism is in doubt. In this study, we examine the use of aldosterone to
      renin ratios in confirming the diagnosis of primary aldosteronism when the usual
      criteria of suppressed renin and elevated aldosterone are not met. We have found
      that an aldosterone to renin ratio of 50 has a 100% specificity and 92%
      sensitivity for detecting primary aldosteronism. Also, an aldosterone to renin
      ratio of > 2000 is suggestive of an aldosterone producing adenoma.

PMID- 9522977
TI  - Coagulation activation, fibrinolysis and inhibitors in neonates.
AB  - Enhanced coagulation activation with reduced antithrombin III (ATIII) activity
      was seen in healthy neonates. Although systemic tissue plasminogen activator (t
      PA) and urokinase-like plasminogen activator (u-PA) levels showed no significant
      differences from normal adults, enhanced fibrinolysis was indicated by elevated D
      dimer and low plasminogen levels in the neonates in this study. Enhanced
      fibrinolysis observed was countered by elevated plasminogen activator inhibitor-I
      (PAI-1) levels, a trend similar to that observed in the amniotic fluid during
      labour. The elevated PAI-1 level seen in neonates may have a beneficial effect in
      preventing haemorrhage in the neonatal period. The haemostatic and fibrinolytic
      mechanisms studied in normal pregnancy neonates were similar to neonates born to
      gestational diabetes mellitus (GDM) mothers. Further studies need to include
      neonates with poor outcome and low Apgar score to assess their haemostatic
      status.

PMID- 9522978
TI  - Computerised analysis of foetal heart rate variation: prediction of adverse
      perinatal outcome in patients undergoing prostaglandin induction of labour at
      term.
AB  - The aim of this study was to determine the value of antenatal numerical
      assessment of foetal heart rate variation in the prediction of adverse perinatal
      outcome in patients undergoing prostaglandin induction of labour at term. Two
      hundred and seven patients who underwent prostaglandin cervical ripening after 37
      weeks gestation for the indications of pregnancy-induced hypertension, foetal
      growth retardation or post-dates pregnancy were included in this study. Prior to
      commencement of cervical ripening, a 30-minute cardiotocography tracing was
      recorded on the System 8000 machine and the long-term and short-term variations
      were calculated. Forty-three patients (20.8%) had a long-term variation of less
      than 30 ms; 9 (4.3%) had a short-term variation of less than 3 ms. The
      sensitivity and positive predictive values of long-term variation in the
      prediction of admission to neonatal special care unit were 25.6% and 23.2%,
      respectively. Corresponding values for short-term variation were 2.6% and 11.1%,
      respectively. The sensitivity and positive predictive values of long-term
      variation in the prediction of caesarean section for foetal distress were 33.3%
      and 9.3%, respectively. Corresponding values for short-term variation were 8.3%
      and 11.1%, respectively. Long-term and short-term variations appeared to be both
      poor predictors of adverse perinatal outcome. However, of 4 foetuses with both
      reduced antenatal heart rate variation and who were subsequently delivered by
      caesarean section for foetal distress in labour, all 4 were admitted to neonatal
      special care unit (NSCU). Foetuses with intrapartum evidence of foetal distress
      were more likely to be admitted to NSCU when antenatal foetal heart rate
      variation was reduced.

PMID- 9522979
TI  - Cervicovaginal foetal fibronectin in the prediction of preterm labour in a low
      risk population.
AB  - The aim of this study was to evaluate the role of cervicovaginal fibronectin as a
      screening test in a low-risk population. Swabs were taken from the posterior
      fornix at 28 weeks gestation and foetal fibronectin levels were assayed using
      enzyme immunoassay. Eighteen patients (7.7%) delivered at less than 37 weeks of
      gestation, and 6 (2.4%) at less than 34 weeks of gestation. Five patients (2.1%)
      had a positive fibronectin test result. The sensitivity, specificity, positive
      predictive value and negative predictive value in the prediction of delivery less
      than 37 weeks of gestation were 16.7%, 99.1%, 60.0% and 93.4%, respectively. The
      sensitivity of foetal fibronectin in the prediction of delivery less than 34
      weeks of gestation was higher (50%) compared with the prediction of delivery less
      than 37 weeks of gestation (16.7%). The low sensitivity of this test suggests a
      limited role for cervicovaginal fibronectin in the low-risk population. Further
      studies need to be carried out to assess whether multiple testing of
      cervicovaginal fibronectin at different gestational ages will further increase
      the sensitivity.

PMID- 9522980
TI  - The ageing worker.
AB  - In Singapore, the age for retirement has increased from 55 years to 60 years, and
      will eventually reach 67 years. At the same time, the proportion of workers aged
      above 45 years will continue to increase. The World Health Organisation has
      reported that in 1980, 32% of the working population were older than 45 years of
      age in countries of the Organisation for Economic Co-operation and Development
      (OECD). This proportion is expected to rise to 35.5% in the year 2000 and 41.3%
      in the year 2055. What are the implications of the emergence of an ageing
      workforce? This population represents a special group of individuals in the
      workforce that have special health, occupational and environmental needs. On the
      one hand, they have the problem of a reduction in physical work capacity,
      decreased adaptability, and a generally lower health status. On the other, ageing
      workers are more experienced and have greater expertise. They are also usually
      more motivated and may generally have a more positive attitude when compared with
      younger workers. Society, as well as health care professionals, needs to respond
      to this issue of an ageing workforce. The response should be three pronged.
      Firstly, prevention of the premature decline of physical capacities and
      adaptability of the worker could be addressed by health promotion and continuing
      job training. Secondly, some measures for adjusting work demands in accordance
      with functional capacities of the individual are needed. Thirdly, employers and
      fellow workers should be educated on the strengths of the ageing worker, and the
      capacity of such workers to continue contributing because of their experience,
      motivation and skills. If implemented, these measures would ensure a path towards
      productive ageing. The end results would be that ageing workers would have their
      functional capacity maintained, the concept of "age-adjusted workload" would be a
      reality, and ageing workers would not be discriminated against, but instead have
      their contributions to society maximised.

PMID- 9522981
TI  - Current concepts in ventilator-associated pneumonia.
AB  - Ventilator-associated pneumonia (VAP) is a common problem in the intensive care
      unit (ICU). It is associated with a distinct spectrum of pathogens and its
      pathogenesis involves microaspiration of oropharyngeal organisms. Clinical and
      radiographic criteria have been shown to be unreliable in diagnosing VAP, and it
      remains a challenge for intensivists to utilise the array of diagnostic
      procedures at their disposal to optimise diagnostic accuracy (improve
      specificity) and guide in therapy. These procedures and guided antibiotic therapy
      may not always improve the outcome and therefore simple preventive measures
      should be employed to reduce the incidence.

PMID- 9522982
TI  - Scrub typhus in the Western Pacific region.
AB  - Scrub typhus is widely endemic in Asia. Man's behaviour and climatic changes
      greatly influenced the occurrence of the disease. Increasing prevalences of scrub
      typhus have been reported from some Asian countries and may coincide with the
      widespread use of beta-lactam antibiotics or to improve diagnostic facilities
      and/or more urbanisation into rural areas. Many cases acquired in Asia surfaced
      in Europe and America. The disease probably is overlooked among paediatric
      patients. Most patients with scrub typhus present with acute fever of unknown
      origin (acute FUO). Eschars are rare among Southeast Asian patients.
      Complications usually develop after the first week of illness. The complications
      include pneumonitis, meningoencephalitis, renal failure and jaundice. Improved
      serologic and molecular diagnostic tests are now available. Although drug
      resistant strain of Orientia tsutsugamushi has been reported, the infection
      usually responds to simple but unpopular drugs such as doxycycline or
      chloramphenicol.

PMID- 9522983
TI  - Update on techniques in the diagnosis of Chlamydia trachomatis infections.
AB  - There are two major advances in the laboratory diagnosis of Chlamydia
      trachomatis, one lies in the use of nucleic acid amplification techniques and the
      second in the evaluation of urine as an alternative to invasive sampling of
      urethral and cervical specimens. There is however, the problem of inhibitors in
      urine that needs to be addressed, in order for this method to achieve 100%
      sensitivity. The Q-beta (Q beta) replicase test, Gen-Probe transcription-mediated
      amplification (TMA) test and the nucleic acid sequence-based amplification
      (NASBA) test are some of the newer nucleic acid amplification methods being
      evaluated for the detection of C. trachomatis. These are RNA-based amplification
      techniques that can potentially achieve very high levels of sensitivity because
      of the presence of multiple RNA copies in microorganisms and may also be useful
      for detecting active infection. Q-beta has been found to be less subjected to
      inhibitory substances in urine than polymerase chain reaction (PCR). Cell culture
      remains the gold standard for the legal diagnosis of C. trachomatis infections
      and is the method of choice for the detection of infection at uncommon sites. It
      forms part of the expanded gold standard for the evaluation of nonculture methods
      that do not involve nucleic acid amplification, and is also a confirmatory test
      for such techniques. Notwithstanding, clinicians must remember the basic tenet of
      laboratory tests, that is, good specimen collection and handling, for any
      laboratory test to yield accurate information to guide their management of
      patients.

PMID- 9522984
TI  - Vancomycin-resistant enterococci.
AB  - Vancomycin-resistant enterococci (VRE) are gaining much attention in the West,
      chiefly because of the lack of available antimicrobial therapy for VRE infections
      as most VRE are also resistant to drugs previously used to treat such diseases
      (e.g. aminoglycosides and ampicillin), the possibility that the vancomycin
      resistant genes present in VRE can be transferred to methicillin-resistant
      Staphylococcus aureus (MRSA), and increasing reports of VRE and the trend towards
      endemicity in North America. There are three case reports and a study showing
      stool carriage of more than 10% from Singapore. One of the case reports is
      notable as the VRE isolated from the urinary tract is community-acquired. In
      Europe, there is a strong association between the use of avoparcin (a
      glycopeptide) in animal feeds and the emergence of VRE. Clonal dissemination
      resulting in nosocomial transmission is also demonstrated. Prior vancomycin use
      is a risk factor for the subsequent development of VRE bacteraemia. The
      laboratory plays an important role, namely, a) detection of VRE, and b)
      determination of susceptibilities of antimicrobials whereby possible therapeutic
      options may be instituted when antimicrobial intervention is indicated. There is
      a need to evaluate existing infection control measures against VRE to prevent it
      from becoming endemic in Singapore as had happened in North America.

PMID- 9522985
TI  - Dengue virus infection--the Malaysian experience.
AB  - Since dengue was first documented in Malaysia in 1902 and made notifiable in
      1973, the disease pattern has changed from major outbreaks every four years to
      one of increasing trend yearly. The largest outbreak was seen in 1996 with 14,255
      dengue cases reported and 32 deaths. The case fatality rate varied from a high of
      10.43% in 1985 when dengue type 3 was the predominant type to a low of 1.29% when
      dengue type 1 predominated. Severe disease patterns have been observed with
      dengue 2 and 3 serotypes in the country. The clinical spectrum has also been
      changing and multisystem involvement with more severe manifestations are being
      seen. Liver involvement has been documented since 1987. Fulminant hepatitis with
      encephalopathy can resemble Reye's syndrome. Dengue type 3 has been isolated from
      liver biopsy specimens. Neurological manifestations can very from irritability,
      convulsions, coma to peripheral neuritis. The isolation of dengue viruses from
      cerebrospinal fluids recently strongly suggests that dengue viruses can be
      neurovirulent. Adult respiratory distress syndrome was seen in three children
      admitted with shock. Deaths were more frequent in children in the early period
      but since 1982, over 50% of deaths have occurred in patients over the age of 15
      years.

PMID- 9522986
TI  - Molecular diagnosis and epidemiology of dengue virus infection.
AB  - Early diagnosis of dengue fever contributes towards appropriate management of the
      disease and its potentially severe complications. Better and more rapid molecular
      procedures are increasingly available for detecting dengue viral RNA, antibodies
      and antigens. Using consensus primers based on the conserved non-structural-3
      gene, the reverse transcription-polymerase chain reaction (RT-PCR) technique can
      amplify all four dengue virus types as well as certain flaviviruses. Consensus
      primers used together with four type-specific downstream primers in single-step
      or semi-nested RT-PCR formats can discriminate the specific dengue virus type by
      virtue of the diagnostic size of the RT-PCR target fragment on agarose gel
      electrophoresis. Alternatively, RT-PCR products may be labelled with digoxigenin
      and allowed to hybridise with individual biotinylated type-specific PCR primers
      which act as capture probes immobilised on solid phase via streptavidin-coated
      tubes. With automated instrumentation for enzyme-linked immunosorbent assay
      (ELISA), the hybridised RT-PCR products can be quantitated spectrophotometrically
      via anti-digoxigenin antibodies conjugated with an enzyme which reacts with
      colourimetric substrate. While RT-PCR is highly sensitive, specific and
      successfully identifies the dengue virus type in clinical serum samples and adult
      Aedes mosquitoes, it generally yields positive results in viraemic sera collected
      within 2 to 5 days of pyrexia. Sera obtained after the period of viraemia are
      more likely to be positive by serological tests such as IgM capture ELISA or the
      commercial Dengue Blot kit. The RT-PCR primers can also be utilised for direct
      cycle dideoxy DNA sequencing to monitor the molecular epidemiology and evolution
      of geographically and temporally separated virus strains. To exemplify this,
      nucleotide and amino acid sequence data as well as phylogenetic trees of several
      strains of dengue 1 and 2 viruses from patients and field-caught Aedes mosquitoes
      are presented.

PMID- 9522987
TI  - Sexually-transmitted diseases in Singapore--trends in the last two decades.
AB  - We review the epidemiology and trends of sexually transmitted diseases (STDs) in
      Singapore from 1977 to 1996. There has been a progressive decline in the
      incidence of bacterial STDs over the period of observation. However, viral STDs
      have not shown the same trends, remaining at a relatively constant level. Early
      detection and treatment of STDs, and health education and prevention measures
      targeting sex workers have been a major factor in controlling STDs. Vigilant
      monitoring of antibiotic resistance patterns in Neisseria gonorrhoeae has allowed
      timely changes to recommended treatment regimens. The advent of the human
      immunodeficiency virus (HIV) infection pandemic in the 1980s and public education
      campaigns have contributed to the success of the STDs control programme. In view
      of the incurable nature of many viral STDs, prevention and counselling have
      become a cornerstone of STD control. Surveillance and monitoring of STD trends
      will continue to provide important information regarding the effectiveness of
      existing health programmes and help us formulate new plans for the future.

PMID- 9522988
TI  - Aesthetic life-like finger and hand prostheses: prosthetic prescription and
      factors influencing choices.
AB  - This paper reviews the authors' experience with fitting life-like finger and hand
      prosthesis. The methodology and technical considerations in producing these
      prostheses, the prosthetic prescription according to the level of amputation and
      the challenges faced with each level are discussed. In cases where the amputation
      is sufficiently distal, a thimble prosthesis has been used. This is compared to
      fitting a full-length finger prosthesis. Besides allowing free range of motion of
      the proximal finger joints which would otherwise be covered and restricted with
      fitting a finger prosthesis, a thimble prosthesis minimises skin coverage for
      optimal sensibility and is easier to don and doff. In cases of amputations where
      a digital fitting is precluded, a partial or a total hand is prescribed. A
      comparison between fitting a finger, a partial hand prosthesis and a total hand
      prosthesis is also discussed. Cases of a digital, transcarpal and a more proximal
      transmetacarpal amputations are relatively easy to fit with a prosthesis. An
      incomplete transmetacarpal amputation where much of the breadth of the hand is
      preserved presents a difficult challenge as it necessitates fitting with a
      partial hand prosthesis. Besides the need to cover a large area of the intact
      skin and the associated problems with reduced sensibility and stump perspiration,
      a partial hand prosthesis is difficult to don and doff.

PMID- 9522989
TI  - A review of free flap failures in the University Hospital, Kuala Lumpur.
AB  - Sixty-one free flaps performed in 59 patients from April 1983 to April 1995 were
      analysed. Various factors that might have affected the outcome of the surgery
      were studied. These included the patient's age, history of smoking, pre-existing
      medical problems such as hypertension and diabetes mellitus, the type of free
      flaps, flap infection, use of postoperative anticoagulation, postoperative
      anaemia and re-exploration. The infection rate was 16.4% and this had a strong
      correlation with the free flap failure in our study population. Postoperative
      anaemia could adversely affect the tissue oxygenation of the free flap and delay
      the re-exploration due to the high anaesthetic risk. Dextran was routinely used
      for postoperative anticoagulation. There were also rescue attempts using heparin
      infusion when needed. The overall failure rate was 13.1%. Besides good
      anaesthetic support, a well-prepared protocol is necessary both for the
      preoperative planning of free flap surgery as well as salvaging a failure.

PMID- 9522990
TI  - A case of unusual electrocardiographic presentation of right ventricular
      myocardial infarction.
AB  - This is a case of an unusual electrocardiographic manifestation of a patient with
      right ventricular (RV) myocardial infarction occurring in association with left
      ventricular inferoposterior myocardial infarction. There was massive ST-segment
      elevation in the precordial leads resembling that of an anterior myocardial
      infarct in addition to the ST-segment elevation seen normally in right
      ventricular leads. Two-dimensional echocardiography confirmed right ventricular
      hypokinesia and coronary angiography revealed single-vessel coronary artery
      disease involving the right coronary artery. It served to remind us that the
      presence of diffuse and massive ST-segment elevation in the precordial leads in a
      patient with inferior myocardial infarction may indicate simultaneous RV
      infarction and warrants further confirmatory tests.

PMID- 9522991
TI  - Isolated hypoglossal nerve palsy in Behcet's disease.
AB  - Isolated hypoglossal nerve paresis as a manifestation of Behcet's disease has not
      been reported. We describe a 42-year-old man with isolated unilateral hypoglossal
      nerve paresis, who had had a five-year history of recurrent orogenital aphthae
      and relapsing arthritic manifestations. It is suggested that the nerve disorder
      represents a form of mononeuritis that may occur in Behcet's disease.

PMID- 9522992
TI  - Duodeno-ureteric fistula secondary to chronic duodenal ulceration.
AB  - Renoalimentary fistulae are rare. When they occur, they are usually between the
      right renal pelvis and the duodenum. The primary pathology often resides in the
      kidney, and nephrectomy is often necessary in the management of such fistulae. We
      describe a case of an elderly man who presented with non-specific abdominal
      pains. He had a history of peptic ulcer which was treated with H2 antagonist. He
      was well for the past few years until recently when he experienced upper
      abdominal pains. Subsequent investigations showed a duodeno-ureteric fistula
      secondary to a chronic duodenal ulcer. The kidney was normal. Polya gastrectomy
      was performed and the patient recovered with complete resolution of his symptoms.

PMID- 9522993
TI  - Re: Vocal cord dysfunction: two case reports.

PMID- 9522994
TI  - Detection of nitric oxide and nitric oxide synthases in psoriasis.
AB  - Biopsies from psoriasis lesions and clinically uninvolved skin of eight patients
      and five normal subjects were studied by immunocytochemistry with computerized
      image analysis for the presence of endothelial, neuronal and inducible isoforms
      of nitric oxide synthase. Endothelial nitric oxide synthase was expressed in the
      endothelium and weakly in some keratinoctyes. Its expression was not
      significantly different in psoriasis. Inducible nitric oxide synthase, however,
      was absent from normal skin but was significantly upregulated in psoriatic
      lesional skin, focally in keratinocytes but to the greatest extent in the
      papillary dermis and to a lesser extent in clinically uninvolved psoriatic skin.
      Inducible nitric oxide synthase staining was greatest in the more severe lesions
      and correlated with the inflammatory infiltrate (CD3-positive cells) and with
      keratinocyte proliferation (Ki-67-positive cells). In normal skin, neuronal
      nitric oxide synthase was expressed only in keratinocytes in the granular layer
      and eccrine sweat glands. However, in psoriasis and clinically uninvolved skin
      the neuronal form was present through all levels of the epidermis. Direct
      measurement of nitric oxide production from the skin surface revealed a tenfold
      increase in the lesions of 16 psoriatic patients compared with their nonlesional
      skin, and this nitric oxide production was inhibited by topical betamethasone.

PMID- 9522995
TI  - Spontaneous release of leukemia inhibitory factor and oncostatin-M is increased
      in supernatants of short-term organ cultures from lesional psoriatic skin.
AB  - Several cytokines are increased in psoriatic skin, mainly at the lesional level.
      Some of these mediators seem to be very important in the pathogenesis of
      psoriasis since they are thought to stimulate keratinocyte proliferation and/or
      to drive the inflammatory changes associated with psoriasis. Among the
      proinflammatory modulators, hematopoietins, which are a family of cytokines
      sharing a receptor component (the gp130 subunit), have been under intensive
      investigation in recent years. The hematopoietin family includes interleukin-6
      (IL-6), interleukin-11 (IL-11,) leukemia inhibitory factor (LIF), oncostatin-M
      (OSM), granulocyte colony-stimulating factor (G-CSF), ciliary neurotrophic factor
      (CNTF) and cardiotrophin. Amounts of two of these molecules, IL-6 and IL-11, have
      been found to be increased in psoriatic lesions. The present study adds new
      information concerning the spontaneous release of two hematopoietins, namely LIF
      and OSM, in 48-h culture supernatants of lesional and nonlesional skin punch
      biopsies from psoriatic patients and normal subjects. The cytokine determinations
      were performed using commercially available ELISA kits. The results are expressed
      as picograms per milligram of tissue, after weight normalization. The levels of
      LIF released by lesional skin (median 2.4 pg/mg, range 0.05-13.4 pg/mg) were
      significantly higher than from nonlesional (median 0.4 pg/mg, range under
      detection limit (UDL)-4.4 pg/mg; P = 0.001) and normal skin (median 0.4 pg/mg,
      range UDL-0.9 pg/mg; P = 0.005). The OSM levels were also significantly higher in
      supernatants of lesional skin (median 0.9 pg/mg, range 0.4-5.2 pg/mg) than in
      supernatants of nonlesional (median 0.2 pg/mg, range UDL-0.8 pg/mg; P = 0.001)
      and normal skin (median 0.1 pg/mg, range UDL-0.4 pg/mg; P = 0.0001). In addition,
      interleukin-8 (IL-8), a cytokine involved in the pathomechanisms of psoriasis,
      showed a similar behaviour when measured in the same samples. Lesional skin
      showed a median value of 752.5 pg/mg, range 98.8-2063.8 pg/mg, nonlesional skin a
      median value of 58.3 pg/mg, range UDL-1252.5 pg/mg (P = 0.007) and normal skin a
      median value of 44.6 pg/mg, range UDL-176.7 pg/mg (P = 0.004). No significant
      differences were found between nonlesional and normal skin for the three
      molecules analyzed. Taken together with the fact that at least two other
      hematopoietins (namely IL-6 and IL-11) are also increased in supernatants of
      lesional psoriatic skin, these data point to a possible involvement of the
      hematopoietins in inflammatory processes associated with psoriasis.

PMID- 9522996
TI  - In vitro reactivity of mast cells in urticaria pigmentosa skin.
AB  - The aim of our study was to evaluate the sensitivity of skin mast cells from
      urticaria pigmentosa (UP) patients to substance P (SP), tumor necrosis factor
      alpha (TNF-alpha) and anti-IgE, and to compare the sensitivity of these cells
      with that of skin mast cells from healthy human donors. Mast cells for in vitro
      functional studies were obtained using an enzymatic dispersion technique from
      skin biopsies (from 11 patients with UP and 11 healthy donors), and the
      reactivity of these cells was estimated on the basis of histamine release. Our
      observations indicated that UP skin mast cells and healthy skin mast cells had
      similar sensitivities to challenge with TNF-alpha at a concentration 10(-7) M
      (16.4% vs 15.2%) and with anti-IgE at a dilution 1:100 (41.0% vs 37.0%). However,
      UP mast cells showed considerably higher sensitivity to challenge with SP at a
      concentration 10(-4) M than healthy skin mast cells (20.0% vs 6.8%), and the
      difference was statistically significant (P < 0.001). UP skin mast cells also
      demonstrated significantly higher spontaneous histamine release than healthy skin
      mast cells (32.1% vs 12.4%, P < 0.001). Our findings indicating UP skin mast cell
      sensitivity to SP might suggest that mechanisms involving neurogenic inflammation
      could contribute to the course of this disease.

PMID- 9522997
TI  - Cadexomer-iodine ointment shows stimulation of epidermal regeneration in
      experimental full-thickness wounds.
AB  - The use of iodine in wound healing is still controversial. Both wound healing
      stimulating effects and toxic effects leading to impaired wound healing have been
      reported. In order to study the direct effects of iodine on wound healing without
      interference of infectious pathogens, we investigated wound-healing parameters in
      noninfected experimental full-thickness wounds in the pig. Topical iodine
      treatment with an ointment consisting of a combination of iodine and cadexomer
      (modified starch), was compared with cadexomer ointment, the vehicle without
      iodine, and with treatment with saline. Treatment lasted for 30 days, followed by
      30 days of wound assessment. The rate of epithelialization, wound contraction,
      systemic iodine absorption and several immunohistochemical markers were
      evaluated. All 36 wounds healed without macroscopic signs of wound infection and
      reepithelialized within 21 days. During the first 9 days of treatment, wounds
      treated with cadexomer-iodine ointment showed significantly more
      epithelialization than the wounds treated with either cadexomer or saline. In
      addition, the epidermis of wounds treated with cadexomer-iodine ointment had
      significantly more epithelial cell layers from day 12 to day 30, and these wounds
      stained for chondroitin sulphate proteoglycans in the newly formed basement
      membrane zone, which was not observed with the other treatments. No negative
      effects of cadexomer-iodine ointment on the formation of granulation tissue,
      neovascularization or wound contraction were observed. During the treatment
      systemic iodine absorption was physiologically acceptable. These results showed
      that treatment with cadexomer-iodine-containing ointment had positive effects on
      epidermal regeneration during the healing of full-thickness wounds in the pig
      compared with ointment alone or saline treatment.

PMID- 9522999
TI  - TNF receptors--how they function and interact.
AB  - Tumor necrosis factor (TNF) is a pleiotropic cytokine regulating various immune
      and inflammatory reactions. It induces cellular responses upon binding to
      specific cell surface receptors of two distinct molecular species--p55 and p75
      TNF receptors (TNF-Rs). Cloning of the respective cDNAs and obtaining the
      receptor-specific molecular tools such a agonistic and blocking monoclonal
      antibodies, TNF muteins with exclusive ability to bind to only one receptor type,
      as well as generation of TNF-R mutants by site-directed mutagenesis enabled
      researchers to answer key questions of the biology of initial steps in the
      cascade of TNF signal transduction. The presented mini-review describes the mode
      of function of the two receptors and discusses the possible ways of interaction
      between them.

PMID- 9523000
TI  - Integrins and bone--cell adhesion and beyond.
AB  - Integrins are a superfamily of cell surface receptors involved in cell-cell and
      cell-matrix adhesion. Integrin-mediated interactions are involved in the
      regulation of numerous cellular functions such as fertilization, implantation,
      cell differentiation and migration during embryonic development, maintaining
      tissue architecture, blood clot formation and retraction programmed cell death,
      tumor growth and metastasis formation, lymphocyte homing and response of cells to
      mechanical stresses. This broad spectrum of activity is achieved by combining the
      ability to create mechanically functional junctions (cell-matrix and cell-cell)
      and signal-transducing capabilities. Osteoblasts and osteoclasts express specific
      integrin receptors and the pattern of expression varies depending on the stage of
      cell differentiation. Interactions of integrins with bone-matrix adhesive
      proteins are thought to be important for regulating the tissue integrity and may
      provide a local, responsive regulatory system of osteoblastic differentiation as
      well. Osteoclasts most likely attach to osteopontin exposed on the bone surface
      via the classic vitronectin receptor alpha v beta 3 and this binding may be
      crucial to their bone resorption activity.

PMID- 9522998
TI  - IL-5 levels in the serum and blister fluid of patients with bullous pemphigoid:
      correlations with eosinophil cationic protein, RANTES, IgE and disease severity.

PMID- 9523001
TI  - Immunological status of septic and trauma patients. II. Proliferative response
      and production of interleukin 6 and tumor necrosis factor alpha by peripheral
      blood mononuclear cells from septic survivor, nonsurvivor and trauma patients: a
      correlation with the survival rate.
AB  - We have studied proliferative response to phytohemagglutinin (PHA) and bacterial
      lipopolysaccharide (LPS) of peripheral blood mononuclear cells (PBMC) and their
      ability to produce IL-6 and TNF-alpha in vitro in: septic survivors, nonsurvivors
      and with multiple injury patients. Blood samples for determination of PBMC
      reactivity were taken upon admission and after 1, 2 and 5 days later. The
      proliferative response of lymphocytes, both spontaneous as well as PHA- and LPS
      induced, was generally higher in septic nonsurvivor patients comparing to other
      groups. Markedly elevated LPS-induced proliferation (particularly on day 3) was a
      bad prognostic sign for survival. The ability of PBMC from the patients to
      produce IL-6 in culture was depressed in nonsurvivor septic patients and elevated
      in trauma patients, comparing to control donors. More profound differences were
      found with respect to TNF-alpha production which was deeply depressed (both
      spontaneous and induced) in septic nonsurvivors. In contrast, TNF-alpha
      production in septic survivors was significantly higher with a peak response on
      day 3. Trauma patients, on the other hand, had significantly increased ability to
      produce TNF-alpha on day 1 and 2, declining thereafter. The data presented in
      this report reveal that low production (or even anergy) with respect to synthesis
      of proinflammatory cytokines in vitro, as well as increased spontaneous
      proliferation of PBMC and proliferation in response to LPS, are significantly
      correlated with the fatal outcome of the septic shock.

PMID- 9523002
TI  - Does cyclophosphamide combined with methylprednisolone affect the expression of
      leukocyte function associated antigen 1 in refractory rheumatoid arthritis.
AB  - In the present study, in order to get a better insight into the mechanism of
      action of cyclophosphamide (CY) in rheumatoid arthritis (RA), we monitored the
      changes in lymphocytes' expression of leukocyte function associated antigen 1
      (LFA-1). A group of 28 patients with refractory severe RA were treated with CY
      and methylprednisolone (MO) intravenously. Using flow cytometry we evaluated the
      changes in LFA-1 molecule expression on peripheral lymphocytes. In the analyzed
      group of patients the proportion of LFA-1 "dim" cells was reduced. After the
      treatment the ratio was partly normalized. Twelve months after cessation of the
      therapy high proportion of LFA-1 "dim" was observed only among CY/MP treated
      patients. The changes were related to clinical improvement. Based on the obtained
      data, it seems, that the treatment affecting the expression of LFA-1 may slow
      down lymphocyte migration and by that limit chronic inflammation within the
      synovium.

PMID- 9523003
TI  - CD3-/HLA-DR+, CD3+/HLA-DR+ cell levels and PHA stimulation of lymphocytes
      obtained from women with recurrent spontaneous abortions and subjected to
      partner's lymphocyte immunization.
AB  - It is assumed that 80% of recurrent spontaneous abortions (RSA) of unknown
      etiology are of immunological origin. The proposed experimental treatment of
      those patients could be immunization with paternal lymphocytes, though the exact
      mechanism through which this therapy exerts its effect is still unknown. Some
      authors suggest that lymphocyte alloimmunization alters the number and activity
      of particular subpopulations of peripheral blood lymphocytes. The aim of this
      study was to evaluate the proliferative O activity of lymphocytes stimulated with
      phytohemagglutinin (PHA) and the percentage of peripheral lymphocytes carrying
      CD3+/HLA-DR+ and CD3-/HLA-DR+ markers, present in 32 selected for this study RSA
      women subjected to paternal lymphocytes' alloimmunization performed prior to
      conception and in early pregnancy. We conclude that, the post-immunization
      changes seem to have different quantitative and qualitative character comparing
      to those seen in normal pregnancy. They seem to avert unfavourable immunological
      phenomena observed in RSA women, allowing for successful continuation of
      pregnancy.

PMID- 9523004
TI  - Polymorphism of the fourth component of complement (C4) and three clinical
      pictures of hepatitis B virus infection in children.
AB  - The fourth component of complement (C4) phenotype and allele frequencies were
      studied in 3 groups of unrelated children affected with hepatitis B virus (HBV)
      infection (25 with glomerulonephritis (GN), 39 with chronic active hepatitis
      (CAH), 24 with Gianotti-Crosti syndrome (GS-S)) and in 100 unrelated healthy
      individuals (H). Ten phenotypes in GN, 14 in CAH, 10 in GC-S and 23 in H were
      found. Some rare phenotypes appeared in the individual cases of ill children.
      Statistical analysis was performed by chi-square test. Each group was compared to
      the others. We found significantly higher frequency of the A3B2,Q0 phenotype in
      CAH than in H as well as significant increase of the A x 4 gene frequency in GC-S
      as compared to H. However, these events could be caused by limited number of
      tested patients. We suspect that the association between C4 alleles and immune
      complex diseases, studied here, does not rather exist.

PMID- 9523005
TI  - Ultrastructure and functional state of rabbit lymphoid cells after repeated
      exposure to lipopolysaccharide and external heating.
AB  - The ultrastructure and proliferative activity of lymphoid tissue cells in rabbits
      after repeated exposures to lipopolysaccharide (LPS) or external heating were
      studied. It was shown that in conditions of the same increase in body temperature
      the production of IL-1-like activity by blood and splenic cells was inhibited to
      the same extent in both groups of animals. It was suggested that one of the
      causes of LPS-induced tolerance may be events provoked by temperature factor per
      se. There were similar changes in activity of epithelial cells in the thymus,
      reticular cells in the spleen, in activation of mast cells in these organs and in
      proliferative processes in the thymus after both exposures, however inhibition of
      proliferative activity of splenic and lymph node cells was observed only in LPS
      treated animals.

PMID- 9523006
TI  - Loss of T cell receptor diminished tumorigenicity of thymocyte-derived lymphoma
      cells in the T cell receptor transgenic mice.
AB  - Mice with transgenic T cell receptor (TCR) recognizing H-Y male antigen developed
      spontaneous lymphomas originated from immature thymocytes, with the surface
      expression of transgenic TCR and CD4/CD8 co-receptors. During in vitro long-term
      culture (3 months) some lymphoma cell lines lost the surface expression of TCR
      and co-receptors. Interestingly, the proteins of transgenic receptor were
      expressed intracellularly but TCR was not detectable on the surface of the in
      vitro selected subline in contrast to TCR-positive parental cells maintained in
      vivo. TCR-negative subline has been found to be slowly growing in vivo (i.p.
      injection) and less tumorigenic (s.c. injection) than parental TCR positive
      lymphoma. It seems that the in vivo interactions of lymphoma cells with
      microenvironment preserve their TCR expression and endow with growth advantage,
      while the selected in vitro TCR-negative cells lose the tumorigenic potential.

PMID- 9523007
TI  - Effect of lactoferrin on proliferation and differentiation of the Jurkat human
      lymphoblastic T cell line.
AB  - The effect of human lactoferrin on the human lymphoblastic T cell line (Jurkat)
      was tested with regard to proliferation and differentiation. Lactoferrin enhanced
      cell proliferation in a serum-reduced (1% fetal calf serum) culture. The
      stimulatory effect of lactoferrin on proliferation depended on the degree of iron
      saturation but the amplitude of the effect was low, similar to that obtained in
      the presence of serum transferrin. The proliferation stimulatory effect of
      lactoferrin was not observed in the presence of 10% fetal calf serum (FCS) in the
      culture medium. These results suggest that Fe-lactoferrin can substitute for Fe
      transferrin during the prolonged culture of cells in a low serum concentration.
      Iron-saturated lactoferrin was also shown to promote T cell differentiation.
      Jurkat cells, when exposed to iron-saturated lactoferrin in the presence of 10%
      FCS, gradually exhibited a decrease in the cell volume, cell surface density of
      CD71 antigen, the nuclear incorporation of [methyl-3H]thymidine, but an increase
      of the percentage of cell population in the G0/1 phase of the cell cycle. These
      modifications were accompanied by the appearance of CD4 antigen at the cell
      surface. Therefore, in the continuous presence of lactoferrin, proliferating
      cells slowly enter into quiescence state, undergoing cell differentiation.

PMID- 9523009
TI  - Investigations on human lutropin from pituitary gland and urine.
AB  - Two newly isolated monoclonal anti-beta hLH antibodies did not recognize both
      human chorionic gonadotropin (hCG) and three synthetic peptide fragments
      corresponding to beta hLH sequence. These antibodies were applied for ELISA of
      human luteinizing hormone (hLH), however, sensitivities of these assays were much
      lower than those with two other monoclonal antibodies obtained earlier in our
      laboratory. No significant differences between assays of hLH from pituitary and
      urine with 6 different pairs of monoclonal antibodies (4 anti-beta and 1 anti
      alpha-subunit) were noticed. The highest hLH concentration in urine samples
      collected during 53 menstrual cycles of 6 women was demonstrated at different
      times of the day. In 14 out of 52 "preovulatory urine" portions, preserved for
      several weeks, over 80% increase of assayed hLH was shown. The highest assays of
      hLH from pituitary and urine were noted at pH 7.5-9.0. Using affinity
      chromatography the whole pituitary hLH was bound to ConA-Sepharose column and was
      eluted with alpha-methyl-D-mannoside as a single peak. However, a small part of
      hLH from urine was eluted from the column as non retarded peak. When HPLC
      analysis with DEAE column was performed, pituitary hLH was separated in two
      fractions while lutropin from urine was eluted as a single peak.

PMID- 9523010
TI  - Further investigations on thymopentin-like fragments of HLA-DQ and their analogs.
AB  - Recently we showed that the fragments of HLA-DQ with the Thr-Pro-Gln-Arg-Gly-Asp
      Val-Tyr-Thr and Gln-Arg-Gly-Asp-Val-Tyr-Thr sequences strongly suppress the
      immune response, while their shorter analogs, Arg-Gly-Asp-Val, Arg-Gly-Asp-Val
      Tyr and Gln-Arg-Gly-Asp-Val-Tyr, show very weak stimulatory activity with respect
      to humoral immunological response. The fragments contain the sequence which is
      very similar to thymopentin (pentapeptide Arg-Lys-Asp-Val-Tyr, an active fragment
      (32-36) of thymopoietin, an immune system activator produced in thymi), and at
      the same time contains the Arg-Gly-Asp (RGD) sequence, known as an inhibitor of
      adhesion processes. In the present study we found that a hexapeptide: Arg-Gly-Asp
      Val-Tyr-Thr is the smallest size fragment of HLA-DQ having both cellular and
      humoral immunosuppressive activity. We also found that linear and cyclic
      fragments of HLA-DQ do not affect cell line production of various cytokines, what
      suggests that the mechanism of interactions of these peptides with the
      immunological system is different as compared with most other known
      immunosuppressors.

PMID- 9523008
TI  - Morphine modulation of thioglycollate-elicited peritoneal inflammation in the
      goldfish, Carassius auratus.
AB  - Intraperitoneal (i.p.) injection of adult goldfish with 3% thioglycollate (TG)
      induces an acute peritoneal inflammation connected with a massive influx of
      inflammatory leukocytes mainly of the head kidney origin. The number of
      peritoneal exudate cells retrieved on day 2 of the inflammatory response is
      significantly lower in fish injected with TG and morphine (20 mg/kg b.w.) than in
      animals injected with TG only. The morphine effect was totally antagonized in
      fish injected 20 min earlier with naltrexone (1 mg/kg), a well-known blocker of
      opioid receptors. Light microscopy of the head kidney Epon sections revealed that
      basophilic granulocytes are common in the control PBS-injected fish and even more
      frequent in fish injected with morphine only. In sharp contrast basophils are
      very rare in the head kidneys from animals with the TG-induced peritoneal
      inflammation, while they are more numerous in fish injected with TG and morphine.
      Supposedly, the basophilic granulocytes might be involved in the inhibitory
      effects of morphine on the acute inflammation in goldfish. An involvement of the
      head kidney in the morphine modulation of the inflammatory response is strongly
      supported by the detection of opioid receptors in the head kidney cells
      suspension.

PMID- 9523011
TI  - Conjugation of the monoclonal antibody 17-1A with the nitroacridine compound C921
      with the poly-L-lysine as an intermediate agent.
AB  - Monoclonal antibody 17-1A specific for human gastric carcinoma was coupled
      directly or indirectly, using poly-L-lysine as an intermediate, with
      nitroacridine compound C921. The aim of the study was to obtain selectively
      cytotoxic immunoconjugates for experimental therapy. Directly coupled conjugates
      retained antibody specificity towards cells of several human adenocarcinoma lines
      but were non cytotoxic in vitro, whereas conjugates obtained with the use of
      intermediate poly-L-lysine expressed only low, non-specific cytotoxicity,
      probably exerted by the poly-L-lysine content.

PMID- 9523013
TI  - Decreased expression of the high-mobility group protein T160 by antisense RNA
      impairs the growth of mouse fibroblasts.
AB  - The T160 protein belongs to the HMG-1 box protein family and preferentially binds
      to non-B-DNA conformations with no sequence specificity. Its exact role has yet
      to be defined, though it seems to participate in processes involving DNA, such as
      replication, transcription and recombination. We have used an antisense RNA
      strategy to investigate its role in cell growth and proliferation. T160
      expression is strongly suppressed by stable introduction of an antisense
      construct into NIH3T3 cells, and this decrease is accompanied by substantial
      changes in the growth properties of the stable transfectants. Impaired growth of
      T160- cells was mainly related to two mechanisms: i) decreased rates of cell
      proliferation at normal serum concentration; and ii) occurrence of cell death by
      apoptosis at low serum concentration, as demonstrated by both flow cytometry and
      microscopy. The finding that decreased T160 availability affects cell
      proliferation, provides further evidence of its involvement in a basic cell
      function, such as DNA replication.

PMID- 9523012
TI  - A set of polyclonal and monoclonal antibodies reveals major differences in post
      translational modification of the rat HNF1 and vHNF1 homeoproteins.
AB  - The related homeodomain-containing transcription factors HNF1 (HNF1 alpha) and
      vHNF1 (HNF1 beta) recognise common target DNA sequences in the regulatory regions
      of many genes and are expressed in several parenchymal cell types, predominantly
      in liver, kidney, intestine and pancreas. HNF1-null mutant mice, with a wild-type
      vHNF1 gene, develop normally, but die within a few weeks of birth with severe
      liver and kidney failure. Humans with a mutation in the HNF1 alpha gene develop
      non-insulin dependent diabetes on maturity (MODY 3). To determine distinctive
      roles for each of these proteins we produced a set of polyclonal sera and
      monoclonal antibodies, directed against different parts of the rat HNF1 and vHNF1
      proteins. These antibodies reveal that HNF1 is present in vivo as a heterogeneous
      mixture of 92-98 kDa molecular mass polypeptides, a mass higher than that
      expected from its amino acid sequence. vHNF1 is present in the form of two
      isoforms of roughly the expected molecular masses, 65 and 68 kDa. In addition,
      some antibodies prepared against bacterially-produced HNF1 recognise vHNF1 but
      not HNF1, in liver and kidney extracts. Hence, we present the first evidence for
      differential post-translational modification of HNF1 and vHNF1 proteins.

PMID- 9523014
TI  - Immunochemical determination of the cellular content of polypeptide chain release
      factor RF3 in Escherichia coli.
AB  - Polypeptide chain termination in Escherichia coli is known to require two codon
      specific release factors, RF1 and RF2. A third factor, RF3, has been described to
      stimulate the termination. Earlier investigations have estimated the cellular
      content of factors RF1 and RF2. Two different immunological techniques for
      measuring the amount of RF3 per cell in crude E coli cell extracts are reported
      here, using a sensitive immunoblotting method and a sandwich assay by ELISA.
      Monoclonal murine antibodies and polyclonal rabbit antibodies were raised against
      extensively purified recombinant E coli RF3. The immunoblotting involves a
      specific monoclonal antibody (mAb), biotinylated second antibody and finally
      radioactive iodinated streptavidin. In the sandwich assay polyclonal antibodies
      are immobilised on a polystyrene surface before addition of crude cell extract; a
      specific mAb serves as primary antibody and an HRP-labelled anti-mouse Ig as
      secondary antibody. Both methods are accurate and rapid to perform. The number of
      RF3 molecules per cell in exponentially growing E coli cells was found to vary
      considerably according to the K12 strain examined and depended on the culture
      medium (from 20 to 500 molecules per cell), faster growth being positively
      correlated with the number of RF3 molecules per cell.

PMID- 9523015
TI  - Cysteinyl-tRNA synthetase from Saccharomyces cerevisiae. Purification,
      characterization and assignment to the genomic sequence YNL247w.
AB  - Cysteinyl-tRNA synthetase (CRS) from Saccharomyces cerevisiae was purified 2300
      fold with a yield of 33%, to a high specific activity (kcat4.3 s-1 at 25 degrees
      C for the aminoacylation of yeast tRNACys). SDS-PAGE revealed a single
      polypeptide corresponding to a molecular mass of 86 kDa. Polyclonal antibodies to
      the purified protein inactivated CRS activity and detected only one polypeptide
      of 86 kDa in a yeast extract subjected to SDS-PAGE followed by immunoblotting. In
      contrast to bacterial CRS which is a monomer of about 50 kDa, the native yeast
      enzyme behaved as a dimer, as assessed by gel filtration and cross-linking. Its
      subunit molecular mass is in good agreement with the value of 87.5 kDa calculated
      for the protein encoded by the yeast genomic sequence YNL247w. The latter was
      previously tentatively assigned to CRS, based on limited sequence similarities to
      the corresponding enzyme from other sources. Determination of the amino acid
      sequence of internal polypeptides derived from the purified yeast enzyme
      confirmed this assignment. Alignment of the primary sequences of prokaryotic and
      yeast CRS reveals that the larger size of the latter is accounted for mostly by
      several insertions within the sequence.

PMID- 9523016
TI  - The effect of different molecular species of sphingomyelin on phospholipase C
      delta 1 activity.
AB  - Bovine brain sphingomyelin was separated into different molecular species using a
      reverse phase column. PLC delta 1 was inhibited by all molecular species of
      sphingomyelin. The extent of this inhibition was dependent on the hydrophobicity.
      Based on fatty acid analysis, we conclude that the inhibition of PLC delta 1
      depends on the chain length and degree of unsaturation of the fatty acid moiety
      of SM. N-palmitoyl-D-sphingomyelin and N-stearoyl-D-sphingomyelin inhibited PLC
      delta 1 less then N-oleoyl-D-sphingomyelin. In the absence of Ca2+ (1 mM EGTA)
      all tested molecular species of SM inhibited weakly the enzyme. The sensitivity
      of PLC delta 1 to inhibition by SM increased with increasing Ca2+ concentration.
      The shape of calcium curve differed for molecular species with saturated and
      unsaturated fatty acids. Inhibition of PLC delta 1 by N-palmitoyl-D-sphingomyelin
      and N-stearoyl-D-sphingomyelin reached a maximum at 0.2 microM Ca2+, while
      inhibition by N-oleoyl-D-sphingomyelin reached maximum at 2 microM Ca2+. PLC
      delta 1 is more sensitive to inhibition by SM when it is maximally activated by
      spermine and calcium and the extent of this inhibition depends on the length and
      degree of fatty acid unsaturation of the molecular species.

PMID- 9523017
TI  - Pig I alpha I appears unmodified in plasma in case of endotoxin-induced
      disseminated intravascular coagulation.
AB  - The unrestricted activity of leukocyte proteinases is thought to contribute to
      the degradation of plasma proteins and thus amplify the coagulation disorders
      occurring in septic shock. Inter-alpha-inhibitor (I alpha I) is a plasma protein
      particularly susceptible to their action. Therefore we investigated its behavior
      in a porcine model of endotoxin shock which reproduces the coagulation changes
      observed in human sepsis. We did not detect any qualitative or quantitative
      modification of porcine I alpha I in plasmas collected from pigs after endotoxin
      infusion. To explain these data, I alpha I was incubated with polymorphonuclear
      neutrophils (PMN) stimulated by FMLP in the presence of cytochalasin B. We found
      that, unlike human PMN, porcine cells were unable to proteolyze I alpha I.
      Moreover, in the incubation medium of pig PMN, triggered either by FMLP or PMA,
      no measurable elastase activity was evidenced. Therefore, we urge to better take
      into account species differences in functional responses of PMN, to explain the
      experimental results obtained in animal models of septic shock.

PMID- 9523018
TI  - Bifunctional structure of two adenylyl cyclases from the myxobacterium
      Stigmatella aurantiaca.
AB  - Two adenylyl cyclase genes (cyaA and cyaB) from the myxobacterium Stigmatella
      aurantiaca were cloned by complementation of Escherichia coli mutants defective
      in the cya gene. cyaA codes for a protein of 424 amino acid residues (AC1), while
      cyaB encodes a protein of 352 residues (AC2). Both cyclases are sensitive to
      adenosine: cAMP production was strongly inhibited in E coli cells and cell
      extracts expressing these genes. AC1 comprises a hydrophobic domain of six
      transmembrane helices coupled to a cytoplasmic catalytic domain endowed with
      adenylyl cyclase activity. A 17 amino acid residue sequence, which is a signature
      of G-protein coupled receptors, as well as of slime mold Dictyostelium discoideum
      cyclic AMP receptors, was found in the membrane domain. AC2 displays features
      also indicating that it is a bifunctional enzyme. The domain located upstream
      from the catalytic adenylyl cyclase domain shows strong similarity to receiver
      modules of response regulators of two-component bacterial signaling systems. In
      vitro mutagenesis of conserved aspartate residues in this domain was shown to
      interfere with cAMP synthesis.

PMID- 9523019
TI  - Echistatin inhibits pp72syk and pp125FAK phosphorylation in fibrinogen-adherent
      platelets.
AB  - The adhesion of ADP-stimulated platelets to immobilized fibrinogen induces the
      tyrosine phosphorylation of multiple proteins which include pp72syk and pp125FAK.
      The phosphorylation of these two proteins increases as function of time of
      platelet adhesion to fibrinogen; however, pp72syk results strongly phosphorylated
      already after 15 min, whereas pp125FAK reaches high levels of phosphorylation
      after 1 h of platelet adhesion. Phosphorylation of both proteins is only slightly
      detectable when platelets are held in suspension or when platelets are allowed to
      adhere to bovine serum albumin, a non-specific substrate. Echistatin, an Arg-Gly
      Asp (RGD)-containing snake-venom protein, affects protein tyrosine
      phosphorylation promoted by platelet adhesion to fibrinogen, by causing an
      approximately 44% and 39% decrease of pp72syk and pp125FAK phosphorylation,
      respectively. The interaction of echistatin with fibrinogen receptor glycoprotein
      IIb-IIIa on platelet surface might be responsible for the block of integrin
      mediated signaling cascade, including pp72syk and pp125FAK inactivation.

PMID- 9523020
TI  - Internal motions of nucleic acid structures and the determination of base-pair
      lifetimes.
AB  - Over the years, imino proton exchange measurements have provided a description of
      base-pair opening and of properties of internal motions of nucleic acids such as
      the individual opening of base pairs and the insensitivity of base-pair lifetimes
      to the nature and stability of neighboring pairs. A recent determination of base
      pair lifetimes in d(CGCGATCGCG) conflicts with the original measurements and
      their interpretation. This question is analyzed in the present work. We emphasize
      the importance of high concentrations of exchange catalyst (eg 1 M NH3) for the
      accurate determination of base-pair lifetimes. These concentrations entail a high
      ionic strength, which can lead to aggregation, enhanced magnetic relaxation and
      underestimation of base-pair lifetimes if exchange is measured by its effect on
      the proton relaxation rate. Magnetization transfer which provides a more direct
      method for the measurement of proton exchange rates is therefore preferred. We
      show that the lack of measurements at high catalyst concentration is responsible
      for the discrepancy mentioned above. Measurements by the magnetization transfer
      method validate the original interpretation and inversion recovery experiments
      illustrate the effect of the ionic strength on the relaxation rate of the imino
      protons.

PMID- 9523021
TI  - Poly(A) dependent translation in rabbit reticulocyte lysate.
AB  - Poly(A) tail has been known to enhance mRNA translation in eukaryotic cells.
      However, the effect of poly(A) tail in in vitro is rather small. Rabbit
      reticulocyte lysate (RRL) is widely used for studying translation in vitro.
      Translation in RRL is typically performed in nuclease-treated lysate in which
      most of the endogenous mRNA have been removed. In this condition, the difference
      in the translational efficiency between poly(A)+ and poly(A)- mRNAs is about two
      fold. We studied the effect of poly(A) tail on luciferase mRNA translation in
      nuclease untreated rabbit reticulocyte lysate, in which endogenous globin mRNAs
      were actively translated. In the case of capped mRNAs, stimulation of translation
      by poly(A) addition was about 1.5- to 1.6-fold and the effect of the poly(A)
      length was small. However, in the case of uncapped mRNAs, the addition of poly(A)
      tail increased luciferase expression over 10-fold. The effect of the poly(A) tail
      was dependent on its length. The difference in the translational efficiency was
      not due to the change of mRNA stability. These data indicate that RRL has the
      potential to translate mRNA in a poly(A) dependent manner.

PMID- 9523022
TI  - The coenzyme A-synthesizing protein complex and its proposed role in CoA
      biosynthesis in bakers' yeast.
AB  - An improved procedure is described for the recovery and purification of the
      coenzyme A-synthesizing protein complex (CoA-SPC) of Saccharomyces cerevisiae
      (bakers' yeast). The molecular mass of the CoA-SPC, determined prior to and
      following its purification, is estimated by Sephacryl S-300 size exclusion
      chromatography to be between 375,000-400,000. Two previously unreported catalytic
      activities attributed to CoA-SPC have been identified. One of these is CoA
      hydrolase activity which catalyzes the hydrolysis of CoA to form 3',5'-ADP and 4'
      phosphopantetheine, and the other is dephospho-CoA-pyrophosphorylase activity
      which catalyzes a reaction between 4'-phosphopantetheine and ATP to form
      dephospho-CoA. The dephospho-CoA then reacts with ATP, catalyzed by the dephospho
      CoA-kinase, to reform CoA. This sequence of reactions, referred to as the CoA/4'
      phosphopantetheine cycle, provides a mechanism by which the 4'-phosphopantetheine
      can be recycled to form CoA. Each turn of the cycle utilizes two mol of ATP and
      produces one mol of ADP, one mol of PPi, and one mol of 3',5'-ADP. Other than the
      hydrolysis of CoA by CoA-SPC, the 4'-phosphopantetheine for the cycle apparently
      could be supplied by alternate sources. One alternate source may be the
      conventional pathway of CoA biosynthesis. Intact CoA-SPC has been separated into
      two segments. One segment is designated apo-CoA-SPC and the other segment segment
      is referred to as the 10,000-15,000 M(r) subunit. The 5'-ADP-4'-pantothenic acid
      synthetase, 5'-ADP-4'-pantothenylcysteine-synthetase, 5'-ADP-4'
      pantothenylcysteine-decarboxylase, and CoA-hydrolase activities reside in the apo
      CoA-SPC segment of CoA-SPC. Whereas the dephospho-CoA-kinase and the dephospho
      CoA-pyrophosphorylase activities reside in the 10,000-15,000 M(r) subunit. Thus,
      the 10,000-15,000 M(r) subunit mimics the bifunctional enzyme complex that
      catalyzes the final two steps in the conventional pathway of CoA biosynthesis.

PMID- 9523024
TI  - alpha-Tocopherol protects against expression of adhesion molecules on neutrophils
      and endothelial cells.
AB  - Leukocyte-endothelial cell interactions, which are mediated by various adhesion
      molecules, are a crucial event in inflammatory reactions including
      atherosclerosis. alpha-tocopherol (alpha-Toc) has been used for therapy of
      vascular diseases because of its antioxidant activity. However, the effect of
      alpha-Toc on inflammatory reactions has not been investigated very well. In the
      present study, we examined the effect of alpha-Toc on expression of adhesion
      molecules on human neutrophils and human umbilical vein endothelial cells
      (HUVEC). Expression of CD11a, CD11b and CD18 on neutrophils was assessed by
      immunofluorescence flow cytometry 30 min after the stimulation of neutrophils
      with 10(-7) M platelet-activating factor (PAF). Surface expression of
      intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1
      (VCAM-1) on HUVEC was evaluated by enzyme immunoassay 8 h after the incubation of
      HUVEC with IL-1 beta (20 U/ml). PAF induced upregulation of CD11b and CD18 on
      neutrophils and IL-1 beta increased surface expression of ICAM-1 and VCAM-1 on
      HUVEC. Coincubation of neutrophils with alpha-Toc and pretreatment of HUVEC with
      alpha-Toc significantly reduced PAF-induced CD11b/CD18 expression and IL-1 beta
      induced upregulation of ICAM-1 and VCAM-1, respectively. These findings indicate
      that alpha-Toc may work as an anti-inflammatory agent through inhibiting
      neutrophil-endothelial cell adhesive reactions.

PMID- 9523023
TI  - Molecular basis of alpha-tocopherol control of smooth muscle cell proliferation.
AB  - Rat and human vascular smooth muscle cell proliferation is specifically sensitive
      to alpha-tocopherol, but not beta-tocopherol. The former, but not the latter, is
      capable of limiting proliferation and inhibiting protein kinase C activity in a
      dose-dependent manner. The phenomenon occurs at concentrations in the range 10-50
      microM. beta-tocopherol addition together with alpha-tocopherol, prevents both
      cell growth and protein kinase C inhibition. alpha-tocopherol increases de novo
      synthesis of protein kinase C molecules. The enzyme specific activity, however,
      is diminished, due to a decreased phosphorylation of protein kinase C, occurring
      in the presence of alpha-tocopherol. Experiments with protein kinase C isoform
      specific inhibitors and precipitating antibodies show that the only isoform
      affected by alpha-tocopherol is protein kinase C-alpha. The effect of alpha
      tocopherol is prevented by okadaic acid indicating a phosphatase of the PP2A type
      as responsible for protein kinase C-alpha dephosphorylation produced in the
      presence of alpha-tocopherol. At a gene level alpha-tocopherol but not beta
      tocopherol induces a transient activation of alpha-tropomyosin gene transcription
      and protein expression. It is proposed that, by inhibiting protein kinase C
      activity via an activation of a phosphatase PP2A, alpha-tocopherol controls
      smooth muscle cell proliferation through changes in gene expression.

PMID- 9523025
TI  - Inhibition of NF-kappa B transcriptional activity by alpha-tocopheryl succinate.
AB  - The role of vitamin E in cell regulation in addition to its function as an
      antioxidant has attracted attention. The effects of alpha-tocopherol (T) and
      alpha-tocopheryl succinate (TS) on transcriptional activation of the tumor
      necrosis factor alpha (TNF-alpha) gene and nuclear factor kappa B (NF-kappa B)
      activation were examined. Two stable transformants were used: TR-1 cells derived
      from THP-1 cells transfected with a vector contains the human TNF-alpha promoter
      (1.4-kb) joined to the human placental alkaline phosphatase (PLAP) coding
      sequence, and B164 cells derived from the same cell line but carrying the vector
      containing the human beta-actin promoter (4.3-kb) as a control. The transfectants
      were cultured in the presence of TS, followed by stimulation with
      lipopolysaccharide (LPS). After stimulation, PLAP activity secreted into the
      culture medium was measured. TS reduced TNF-alpha transcriptional activity in a
      concentration-dependent manner, while no effect was observed on that of the beta
      actin promoter. Gel shift assay revealed that THP-1 cells pretreated with TS and
      then with LPS showed inhibition of NF-kappa B activity by 43% at 50 microM versus
      the TS-untreated group. Since TS did not affect activator protein-1 (AP-1)
      activity under the same conditions, the inhibitory effect of TS on NF-kappa B
      activation might be specific. However, T had no effect on the results of the gel
      shift assay. Vitamin E transportation was analyzed by simultaneous determination
      of vitamin E and its derivatives using HPLC. The vitamin E recovered from culture
      pellets showed almost the same amounts of T and TS transferred and was recovered
      in unchanged form. These observations indicated that TS inhibited NF-kappa B
      activation and/or translocation to the nuclei in its unchanged form under the
      culture conditions used here. These results suggested that vitamin E is involved
      in signal transduction via an effect distinct from its antioxidant function. To
      explain the lack of activity with T, it remains to be clarified whether
      physiological incorporation of T occurred.

PMID- 9523026
TI  - Singlet oxygen scavenging by alpha-tocopherol and beta-carotene: kinetic studies
      in phospholipid membranes and ethanol solution.
AB  - The rate constants (ks) of 1O2 scavenging for alpha-tocopherol (alpha-Toc) and
      beta-carotene (beta-Car) were measured in liposome membranes, and compared with
      those in EtOH solution. 1O2 was site-specifically generated by photoirradiation
      using two photosensitizers, water-soluble Rose bengal (RB) and lipid-soluble 12
      (1-pyrene)-dodecanoic acid (PDA). The ks value for beta-Car in EtOH solution was
      1.3 x 10(10) M-1 s-1, which was 36 times that for alpha-Toc (3.6 x 10(8) M-1 s
      1), but there was no difference between their ks values in liposomes (1.8 x 10(7)
      M-1 s-1 for beta-Car and 1.2 x 10(7) M-1 s-1 for alpha-Toc). In the liposomes,
      the ks value for alpha-Toc was affected by the membrane site where 1O2 was
      generated, which depended on the localization of the photosensitizer, being high
      at the membrane surface in the RB-system and low in the inner region of the
      membrane in the PDA-system. In contrast, the ks value for beta-Car was not
      affected by the 1O2-generating site. These differences were supposed to be caused
      by differences in the relative concentrations of 1O2 and active sites of alpha
      Toc and beta-Car in the membranes. alpha-Toc and beta-Car inhibited 1O2-dependent
      peroxidation of egg yolk phosphatidylcholine (egg PC). The concentrations of
      alpha-Toc required for 50% inhibition of lipid peroxidation (IC50) were higher
      than those of beta-Car, being more than 6 times higher in EtOH solution and less
      than 2 times higher in liposomes. The ratio of the antioxidant activity of beta
      Car to that of alpha-Toc was more in EtOH solution than in liposomes, and was
      well correlated with the ratio of their 1O2 scavenging rate constants.

PMID- 9523027
TI  - Action of vitamin E as antioxidant against oxidative modification of low density
      lipoprotein.

PMID- 9523028
TI  - Effect of supplementation with vitamin E on LDL oxidizability and prevention of
      atherosclerosis.
AB  - Supplementation of LDL with vitamin E is thought to protect LDL from oxidative
      modification and prevent the development of atherosclerosis. Large
      epidemiological studies have revealed that vitamin E levels in plasma are
      inversely correlated to the incidence of coronary heart disease. Double-blind
      placebo-controlled trials have reported that supplementation with vitamin E
      decreases the incidence of coronary events in coronary heart disease (CHD)
      patients. However, it is not clear how high a dose of vitamin E is needed to
      prevent formation of atherosclerosis. In animal studies, a diet containing 0.125%
      vitamin E increased its levels in plasma two-fold and prevented formation of
      early atherosclerotic lesions in the thoracic aorta of hypercholesterolemic
      rabbits. Dose-response studies in humans have reported that 400 IU/day vitamin E
      increased its levels in plasma two-fold and prolonged the lag time before LDL
      oxidation. It has been reported that oxidizability of LDL was correlated to the
      atherosclerotic score of coronary angiography in CHD patients. About 400 IU/day
      vitamin E, which increases its levels two-fold and prolongs sufficiently the lag
      time before LDL oxidation, might be beneficial in decreasing the individual risk
      of CHD.

PMID- 9523029
TI  - Prevention of diabetes-induced abnormal retinal blood flow by treatment with d
      alpha-tocopherol.
AB  - Hyperglycemia in diabetes mellitus has been shown to activate diacylglycerol
      (DAG)-protein kinase C (PKC) pathway in the vascular tissues, possibly altering
      vascular function. We have characterized the effects of vitamin E (d-alpha
      tocopherol) on activation of PKC and DAG levels in retinal tissues of diabetic
      rats, and correlated its effects to retinal hemodynamics using video-based
      fluorescein angiography (VFA). Comparing streptozotocin-induced diabetic rats to
      controls, membranous PKC specific activities were increased by 71% (p < 0.05).
      Western blot analysis showed that the membranous PKC beta II isoform was
      significantly increased by 133 +/- 45% (p < 0.05). Intraperitoneal injection of d
      alpha-tocopherol (40 mg/kg) every other day prevented the increases in membranous
      PKC specific activity and PKC beta II protein shown by immunoblots. Similar to
      PKC activities, total DAG levels were increased in the retina and were normalized
      by d-alpha-tocopherol treatment. Physiologically, abnormalities of retinal blood
      hemodynamics, as measured using VFA, which previously have been reported to be
      associated with increases of DAG and PKC levels in the diabetic rats, were
      prevented by d-alpha-tocopherol treatment in diabetic rats. The direct effect of
      d-alpha-tocopherol on total DAG and [3H]-palmitate incorporation into DAG were
      also examined using cultured bovine retinal endothelial cells (REC). Exposure of
      REC to 22 mM glucose for three days increased total DAG and [3H]-palmitate
      labeled DAG levels by 35 +/- 8% and 50 +/- 8%, respectively (p < 0.05). The
      presence of d-alpha-tocopherol (50 micrograms/ml) prevented the increase of both
      total DAG and [3H]-palmitate labeled DAG levels in cells exposed to 22 mM
      glucose. These findings suggested that the mechanism of the d-alpha-tocopherol's
      effect appears to be mediated by the normalization of the hyperglycemia-induced
      activation of the DAG-PKC pathway which leads to the normalization of abnormal
      retinal blood flow seen in diabetes mellitus.

PMID- 9523030
TI  - d-alpha-tocopherol treatment prevents glomerular dysfunctions in diabetic rats
      through inhibition of protein kinase C-diacylglycerol pathway.
AB  - Since diabetes now accounts for 35% of all new cases of end-stage renal disease
      in the United States, it is really important to prevent the onset of diabetic
      nephropathy. Activation of protein kinase C (PKC) is implicated to be one of the
      causal factors in the development of renal dysfunctions in diabetes. In this
      study, we have demonstrated that total diacylglycerol (DAG) contents and PKC
      activity in glomeruli were significantly increased in diabetic rats as compared
      to control rats, but intraperitoneal injection of d-alpha-tocopherol prevented
      these biochemical abnormalities in parallel with normalization of glomerular
      dysfunction such as increased glomerular filtration rate (GFR) in diabetic rats.
      Albuminuria in diabetic rats was also significantly increased as compared to
      control rats, whereas d-alpha-tocopherol treatment again ameriolated increased
      albuminuria in parallel with the inhibition of glomerular PKC activation by
      diabetes. Moreover, we have observed that the activity of DAG kinase, which
      metabolizes DAG to phosphatidic acid and acts as an attenuator for the DAG-PKC
      pathway, was enhanced by d-alpha-tocopherol treatment. These results suggest that
      the increase in the DAG-PKC pathway might play an important role for the
      development of glomerular dysfunctions in diabetes and d-alpha-tocopherol
      treatment could be helpful in diabetic nephropathy.

PMID- 9523032
TI  - Developmental changes in the expression of alpha-tocopherol transfer protein
      during the neonatal period of rat.
AB  - It is well known that the cellular concentration of alpha-tocopherol (alpha-toc)
      is about 10-fold greater than that of gamma-tocopherol (gamma-toc) despite the
      ingestion of a large amount of gamma-toc in the diet. Recently, this
      discrimination of tocopherol is considered to be attributed to alpha-tocopherol
      transfer protein (alpha-TTP) which binds to alpha-toc in preference to the other
      forms of tocopherol in the liver. In the present study, developmental changes in
      expression of alpha-TTP after birth were investigated using rats with respect to
      plasma changes of tocopherols. The expression of alpha-TTP in the neonatal rat
      liver, which was very low immediately after birth, increased steadily during the
      two weeks of life before weanling and reached the adult level at four weeks.
      During the suckling period, the plasma ratio of alpha-toc to gamma-toc linearly
      increased, because plasma alpha-toc which was low immediately after birth,
      increased rapidly during the period, while gamma-toc remained unchanged. The
      increase in the ratio seemed to correlate with the developmental expression of
      alpha-TTP in the liver during this period.

PMID- 9523031
TI  - The role of vitamin E in T-cell differentiation and the decrease of cellular
      immunity with aging.
AB  - The purpose of this study is to investigate the effects of vitamin E on both the
      decrease of cellular immunity with aging (Section 2) and the differentiation of T
      cells in thymus (Section 3). In Section 2, spontaneously hypertensive rats (SHR)
      as a model for aging were used in this experiment and fed regular (50 IU/kg diet)
      or a high vitamin E (500 IU/kg diet) diet for 6 weeks. At 12 weeks old, they were
      killed and assayed. Although proliferation of thymic lymphocytes was
      significantly decreased in SHR fed the regular diet compared to that of Wistar
      Kyoto rats (WKY) fed the same diet, the high vitamin E diet induced higher
      proliferation of thymic lymphocytes in SHR, which was almost the same as that of
      WKY fed the regular diet. In addition, the expressions of both CD4 and CD8
      antigens on CD4+ CD8+ T-cells were also decreased in SHR, which was significantly
      improved by a high vitamin E diet. These results suggest that a high vitamin E
      diet enhances thymic lymphocyte proliferation through increased T-cell
      differentiation in the thymus. Then, the effect of vitamin E on T-cell
      differentiation in the thymus was investigated by using male Fisher rats. Rats
      were divided into three groups; vitamin E-free, regular and high vitamin E groups
      and fed a diet containing various levels of vitamin E (0, 50 and 500 IU/kg diet)
      for 7 weeks. Although the proportions of CD4+ CD8- and CD4- CD8+ T-cells in
      thymocytes were significantly greater in the high vitamin E group, the proportion
      of CD4+ CD8- T-cells inversely decreased in the vitamin E-free group compared to
      that of the regular group. We have tried to investigate the mechanism on the
      increased T-cell differentiation in the thymus of rats fed the high vitamin E
      diet through cytokine production, thymic epithelial cell (TEC) and macrophage
      functions. As their results, we have found that vitamin E enhances T-cell
      differentiation through the increase of not macrophage but TEC function in the
      thymus, which is associated with the increased binding capacity of TEC to
      immature T-cells via increased expression of the adhesion molecule, ICAM-1. These
      results suggest that vitamin E is a potent nutrient for promoting health in the
      aged via the improvement of cellular immunity decreased with aging.

PMID- 9523033
TI  - Can antioxidant supplementation slow the aging process?
AB  - The oxidative stress theory of aging is well supported by accumulated evidence
      from various aging intervention studies. Early antioxidant supplementation
      studies indicate life span extensions by antioxidant feeding in various
      experimental organisms. Data collected under tightly controlled conditions show
      that the feeding of 2-mercaptoethanol (0.25%) effectively prolonged both the
      median and maximum life spans of mice. Evidence has been obtained showing dietary
      vitamin E to protect against oxidative damage to DNA in human lymphocytes and
      white blood cells. Other clear evidence of vitamin E's protective effect has been
      seen in its suppressive action of LDL oxidation both in vitro and in vivo. New
      evidence on the physiological roles of antioxidants, in addition to their well
      known role as free radical scavengers, is emerging from recent research. For
      instance, the beneficial effect of vitamin E in improving glucose transport and
      the insulin sensitivity and its putative role as a regulator of cell
      proliferation should open new research dimensions. This presentation will review
      some of the anti-aging aspects of dietary antioxidant supplementation, as well as
      the potential problems of its long-term administration that stem from our lack of
      knowledge about free radical metabolism and the regulation of endogenous defense
      mechanisms.

PMID- 9523034
TI  - Aging and oxidative stress in neurodegeneration.
AB  - The effect of oxidative stress on the function of brain synapse, the difference
      in susceptibility of synapse to hyperoxia with age, and the changes in vitamin E
      status by stress and aging were investigated. Synaptic membrane permeability to
      sucrose was increased with age. When rats were subjected to hyperoxia, the
      membrane permeability on each age increased significantly. The susceptibility of
      synapse of 25 month old rats exposed to stress was about 2.5 times higher than
      unexposed old rats. The synaptic plasma membrane fluidity decreased significantly
      either in response to hyperoxia or during aging. The thiobarbituric acid reactive
      substances (TBARS) in the synaptic plasma membranes increased with age, and those
      in the membranes of oxygen-exposed rats were higher than in the unexposed rats.
      The cholesterol/phospholipids (C/P) ratio of the membranes increased
      significantly with age, and the values in the membranes of oxygen-exposed rats
      increased more significantly than in unexposed rats of each age. In a measurement
      of fatty acid content in the membranes, the content of docosahexaenoic acid (DHA,
      C22:6) decreased significantly during aging and by hyperoxia. These results
      suggest that free radicals derived from oxygen may attack nerve terminals and
      peroxidize the membrane, resulting in the deterioration of function of brain
      synapse, and that susceptibility of synapse to oxidative stress was significantly
      increased with age. Vitamin E content in the synaptic plasma membranes decreased
      with age. When rats were subjected to oxidative stress, the content was lower in
      each age than in normal rat membranes. An intraperitoneal administration of
      vitamin E prior to stress reduced these abnormalities. It is obvious that vitamin
      E contributes to the protection against nerve terminal dysfunction caused by
      oxidative stress.

PMID- 9523035
TI  - Vitamins E plus C and interacting conutrients required for optimal health. A
      critical and constructive review of epidemiology and supplementation data
      regarding cardiovascular disease and cancer.
AB  - Antioxidants are crucial components of fruit/vegetable rich diets preventing
      cardiovascular disease (CVD) and cancer: plasma vitamins C, E, carotenoids from
      diet correlate prevalence of CVD and cancer inversely, low levels predict an
      increased risk of individuals which is potentiated by combined inadequacy (e.g.,
      vitamins C + E, C + carotene, A + carotene); self-prescribed rectification of
      vitamins C and E at adequacy of other micronutrients reduce forthcoming CVD, of
      vitamins A, C, E, carotene and conutrients also cancer; randomized exclusive
      supplementation of beta-carotene +/- vitamin A or E lack benefits except prostate
      cancer reduction by vitamin E, and overall cancer reduction by selenium;
      randomized intervention with synchronous rectification of vitamins A + C + E + B
      + minerals reduces CVD and counteracts precancerous lesions; high vitamin E
      supplements reveal potentials in secondary CVD prevention. Plasma values
      desirable for primary prevention: > or = 30 mumol/l lipid-standardized vitamin E
      (alpha-tocopherol/cholesterol > or = 5.0 mumol/mmol); > or = 50 mumol/l vitamin C
      aiming at vitamin C/vitamin E ratio > 1.3-1.5; > or = 0.4 mumol/l beta- (> or =
      0.5 mumol/l alpha+ beta-) carotene. CONCLUSIONS: In CVD vitamin E acts as first
      risk discriminator, vitamin C as second one; optimal health requires
      synchronously optimized vitamins C + E, A, carotenoids and vegetable conutrients.

PMID- 9523036
TI  - A personal overview of vitamin E research.

PMID- 9523037
TI  - Desperately seeking difference.

PMID- 9523038
TI  - Difficult difference.

PMID- 9523040
TI  - Social class and medical decisionmaking: a neglected topic in bioethics.

PMID- 9523039
TI  - The difference that culture can make in end-of-life decisionmaking.

PMID- 9523041
TI  - The religious difference in clinical healthcare.

PMID- 9523043
TI  - Distracted by disability. The "difference" of disability in the medical setting.

PMID- 9523042
TI  - Approximation and negotiation: clinical pragmatism and difference.

PMID- 9523044
TI  - CQ sources/bibliography.

PMID- 9523045
TI  - Response to "Dimensions and classification of genetic interventions in the human
      genome" by Matthew D. Bacchetta and Gerd Richter (CQ vol. 5, no. 3)

PMID- 9523046
TI  - Response to "Ethics and drug infants" by Michelle Oberman (CQ vol. 6, no. 2)

PMID- 9523047
TI  - A crossroads in genetic counseling and ethics.

PMID- 9523048
TI  - Mass pre-embryo adoption.

PMID- 9523049
TI  - The status of hospital ethics committees in Pennsylvania.

PMID- 9523051
TI  - Migraine headaches: epidemiology and comorbidity.
AB  - Migraine imposes substantial burdens both on individual headache sufferers and on
      society. Prevalence studies reveal that the condition affects about 18% of women
      and about 6% of men. Prevalence is highest between the ages of 25 and 55, during
      the peak productive years. Despite the development of new and effective treatment
      options, migraine remains an underdiagnosed and undertreated condition. In this
      article, we review the incidence, prevalence, and distribution of migraine and
      the conditions which are comorbid with migraine.

PMID- 9523052
TI  - Cortical electrophysiology in migraine and possible pathogenetic implications.
AB  - According to recent evoked potential studies a fundamental, probably protective,
      feature of cortical information processing, i.e., 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 potential 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 propose 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, 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- 9523053
TI  - Serotonin receptors and the acute attack of migraine.
AB  - The development of serotonin (5HT) agonists that have highly specific receptor
      profiles has fueled the study of 5HT receptor pharmacology and in particular the
      pharmacology of the 5HT1 sub-class of receptors. The currently accepted
      classification of 5HT receptors includes seven classes known as 5HT1 through 5HT7
      and the class most implicated in migraine 5HT1, which consists of the A, B, D, E,
      and F sub-types. Currently, effective and relatively specific anti-migraine
      compounds, as a group, are potent 5HT1B/1D agonists. Their possible mechanisms of
      action include carotid territory vasoconstrictor effects and inhibitory effects
      on both the peripheral and central terminals of the trigeminal innervation of the
      pain-producing intracranial structures. Future drug development will target these
      individual mechanisms to dissect out which, if any, determines the clinical
      efficacy of the compounds.

PMID- 9523054
TI  - Role of magnesium in the pathogenesis and treatment of migraines.
AB  - The importance of magnesium in the pathogenesis of migraine headaches is clearly
      established by a large number of clinical and experimental studies. However, the
      precise role of various effects of low magnesium levels in the development of
      migraines remains to be discovered. Magnesium concentration has an effect on
      serotonin receptors, nitric oxide synthesis and release, NMDA receptors, and a
      variety of other migraine related receptors and neurotransmitters. The available
      evidence suggests that up to 50% of patients during an acute migraine attack have
      lowered levels of ionized magnesium. Infusion of magnesium results in a rapid and
      sustained relief of an acute migraine in such patients. Two double-blind studies
      suggest that chronic oral magnesium supplementation may also reduce the frequency
      of migraine headaches. Because of an excellent safety profile and low cost and
      despite the lack of definitive studies, we feel that a trial of oral magnesium
      supplementation can be recommended to a majority of migraine sufferers.
      Refractory patients can sometimes benefit from intravenous infusions of magnesium
      sulfate.

PMID- 9523055
TI  - Nitric oxide theory of migraine.
AB  - The molecular mechanisms of migraine pain have not yet been clarified. Neurogenic
      inflammation and a subsequent plasma extravasation in the dura mater have been
      suggested. However, monoamine and peptide neurotransmitters involved in
      neurogenic inflammation do not cause significant head pain. Based on our previous
      studies of headache induced by i.v.infusions of glyceryl trinitrate (exogenous
      nitric oxide donor) and histamine (which liberates nitric oxide from vascular
      endothelium), we suggest that nitric oxide (NO) is a more likely candidate
      molecule. The present review deals with the biology of this small messenger
      molecule and the scientific evidence suggesting a key role for this molecule in
      migraine headache. We hypothesise that the release of NO from either blood
      vessels, perivascular nerve endings, or brain tissue is a molecule trigger
      mechanism of spontaneous migraine pain. These novel observations dictate new
      approaches to the pharmacological treatment of migraine.

PMID- 9523056
TI  - Genetic basis of migraine.
AB  - Rapid technological advances in the field of molecular genetics are being applied
      successfully to the analysis of migraine. Specific mutations leading to an
      increased risk of rare forms of migraine have been identified in both
      mitochondrial DNA and a calcium channel gene. Association studies have
      demonstrated that polymorphic variations in serotonergic and dopaminergic genes
      may alter the clinical susceptibility to migraine. Massive amounts of additional
      genetic data relating to migraine will be generated in the next few years. These
      data are revolutionizing the diagnosis and management of migraine, a heretofore
      subjective clinical disorder.

PMID- 9523057
TI  - Quality of life in migraine.
AB  - Health-related quality of life (QoL) is becoming an important outcome measure in
      the field of migraine. Several generic and migraine-specific questionnaires have
      been evaluated for reliability and validity in migraine. The generic instruments
      demonstrate the severe impairment in the QoL of migraine patients compared to
      patients with other chronic diseases and to the general population. The migraine
      specific instruments are designed to measure the short- and long-term impact of
      migraine on QoL and are responsive to changes in QoL secondary to migraine
      therapy. The widespread use of these standardized instruments can increase
      awareness of the burden of migraine and lead to improved therapeutic intervention
      for migraine.

PMID- 9523058
TI  - Non-pharmacological treatment of headaches--why?
AB  - Headache and mood disorders co-occur at significant rates. Two psychological
      techniques of proven effectiveness in treating headache are biofeedback and
      relaxation training. For treating the mood disorders that accompany chronic
      headache, cognitive-behavioral and pharmacological therapies are highly effective
      both individually and combined. The present article discusses the importance of
      treating anxiety-spectrum disorders as well as pain when treating headache, and
      of manipulating factors known to influence the probability of a patient's
      developing chronic pain and disability.

PMID- 9523059
TI  - Management of an acute primary headache.
AB  - Effective management of primary (benign) headaches generally depends upon proper
      diagnosis and rational use of medications. Successful treatment requires adequate
      dosing plus choosing the optimal route for drug delivery. When oral remedies
      fail, transnasal, rectal, or parenteral therapy may succeed. While cure of
      headaches is not currently possible, control is possible for the majority of
      sufferers. Most patients can adequately treat their headaches without resorting
      to the doctor's office or emergency room. Many therapies may not only relieve
      head pain, but also alleviate associated symptoms.

PMID- 9523060
TI  - Pharmacological prevention of migraine.
AB  - Although abortive treatment and nonpharmacologic interventions are effective for
      many if not most patients' occasional migraine attacks, patients who have
      frequent and/or severe attacks may benefit from preventive pharmacotherapy. This
      is particularly critical for those patients whose migraines are not treated
      effectively by acute-care medications because lack of pain control may lead to
      overuse syndromes that complicate further treatment. Inappropriate use of acute
      care medication may contribute to chronic daily headache, tolerance to
      symptomatic medication, and headache refractory to all treatment. In addition,
      patients who increase use of acute-care medication due to lack of effect may
      suffer ergotism, GI problems, liver toxicity, analgesic nephropathy, drug induced
      headache, and withdrawal symptoms when overused agents are withdrawn. Finally,
      overuse of acute-care medication may interfere with the effectiveness of
      preventive medication. The remainder of this article will focus on when to treat
      with preventive medication and which medications are currently available for
      prevention of migraine.

PMID- 9523061
TI  - Death in custody.
AB  - Death in custody is the most demanding investigation that a medical examiner or
      coroner can perform. The investigation requires attention to detail at the time
      of scene investigation and autopsy examination, as well as a careful assessment
      of the toxicologic results and circumstances of the death. Synthesis of the many
      facts that are developed during the investigation should allow the medical
      examiner or coroner to establish a reasonable cause of death. There can be
      legitimate points of disagreement of interpretation because the conclusions so
      frequently are predicated on physiologic processes and not on anatomic findings.
      It is incumbent on the medical examiner and coroner responsible for investigating
      deaths of these types to utilize all the information generated during the
      investigation and to identify an appropriate cause of death.

PMID- 9523062
TI  - Epidemiologic aspects of forensic pathology.
AB  - Forensic pathologists have made great contributions to epidemiologic research and
      will undoubtedly continue to do so by providing information that can help to
      describe, explain, predict, and control the occurrence of specific disorders.
      Greater funding is needed, however, to realize the potential applications of
      forensic pathology to epidemiologic research. Public health officials have only
      recently recognized what forensic pathologists have known for a long time and
      what Hirsch has recently stated: the public health aspects of forensic pathology,
      which include epidemiologic research, exemplify "forensic pathology at its best."

PMID- 9523063
TI  - Traumatic neuropathology.
AB  - The neuropathology of trauma is reviewed based on the mechanism of injury.
      Pathology is divided into primary and secondary injury, based on the relationship
      to the time of injury. It is further divided by mechanism, with primary impact
      injury including skull fracture, epidural hematoma, brain contusion and
      laceration, and intracerebral hemorrhage; primary inertial injury including
      subdural hematoma, diffuse axonal injury, and diffuse vascular injury; and
      secondary injury including hypoxia/ischemia, brain swelling, infection, and
      increased intracranial pressure. The neuropathology of child abuse is also
      reviewed.

PMID- 9523064
TI  - Forensic science. An overview of new technology and instrumentation for the
      forensic pathologist.
AB  - The use of computerized databases in the areas such as, fingerprint
      identification, firearms identification and DNA analysis will change the role of
      the forensic practitioner in the future. The forensic scientist will direct
      investigations by making associations, through use of these databases, with other
      crimes, both locally and nationally. Computer systems will also make it easier
      for the forensic scientist to demonstrate to the jury the significance of
      individual items of evidence as well as their relationship with each other and
      items from other cases.

PMID- 9523065
TI  - Forensic pathology of heat-and cold-related injuries.
AB  - The human body must maintain a relatively constant temperature to function. The
      thermoregulatory system plus human behavior control the balance of heat loss and
      heat gain. Heat is produced at a relatively constant rate by the body's basal
      metabolism. Heat production can be increased by increasing skeletal muscular
      activity. Heat is lost from the body to the environment by conduction,
      convection, radiation, and evaporation. Illness due to heat stress develops when
      the body gains more heat than it loses. Illness due to cold stress develops when
      the body loses more heat than it can produce or gain from external sources.
      During periods of extreme heat, mortality may rise sharply, sometimes to epidemic
      proportions. Because nearly all heat-related deaths are preventable, early
      detection of these deaths will allow appropriate preventive measures to be
      implemented. The autopsy findings in both heat-related and cold-related deaths
      are nonspecific. Information about environmental conditions, scene investigation,
      and the available medical history are very important in formulating the
      diagnosis.

PMID- 9523066
TI  - Informatics. Using the Internet for forensic sciences.
AB  - This article deals with the elementary concepts of the use of Internet
      informatics for communication of information between individuals having an
      interest in forensics. The use of the Internet for purposes of e-mail and news
      group communication, Medline literature search, information search of the
      Internet for areas of interest, Web sites of interest to forensic-based
      personnel, and the availability of File Transfer Protocols are briefly discussed.

PMID- 9523067
TI  - The pathology of terrorism. Acts of violence directed against citizens of the
      United States while abroad.
AB  - Acts of terrorism resulting in serious injury and death have become a daily
      occurrence in the late 1990s. Forensic pathologists play a key role in the
      investigation and eventual prosecution of such cases. Meticulous attention to
      injuries as well as photographic documentation of findings along with the
      recognition and recovery of trace evidence are critical parts of the autopsy on
      the victims of terrorist violence. Specific cases of terrorist events from the
      period of 1985-1007 are presented along with a detailed explanation of explosion
      related injuries.

PMID- 9523068
TI  - Postmortem identifications of remains.
AB  - Forensic pathologists must identify the bodies and remains falling under their
      purview in the normal course of death investigation and death certification.
      Accurate identification is critical and can at times be daunting challenge,
      especially in mass disaster situations. Many methods can be employed from various
      scientific disciplines and otherwise, resulting in positive or presumptive
      identification. Then, proper identification must be maintained and supported
      where challenged.

PMID- 9523069
TI  - Actions for damages against medical examiners and the defense of sovereign
      immunity.
AB  - The doctrine of sovereign or official immunity has protected medical examiners in
      cases alleging negligent performance of the autopsy and in cases involving
      negligent harvesting of organs. It has not protected examiners in cases alleging
      performance of autopsy without authorization. The medical examiner, therefore, is
      well advised to determine whether there may be any objection by the next-of-kin
      to an autopsy and particularly any religious objection-and if there is such an
      objection, to proceed only after making contemporaneous and documented decision
      that there is a compelling need for the autopsy.

PMID- 9523070
TI  - Image processing in forensic pathology.
AB  - Image processing applications in forensic pathology are becoming increasingly
      important. This article introduces basic concepts in image processing as applied
      to problems in forensic pathology in a non-mathematical context. Discussions of
      contrast enhancement, digital encoding, compression, deblurring, and other topics
      are presented.

PMID- 9523071
TI  - Controversies in neonatal resuscitation.
AB  - In the delivery room, pediatricians are frequently required to make immediate
      decisions about resuscitating infants. Is the baby too small, too immature, or
      too asphyxiated to be revived? To achieve the best outcome, resuscitation once
      initiated, must be performed expeditiously, safely, and with the utmost
      diligence. Not all the tools and medications have undergone the intense scrutiny
      that might otherwise be assumed. In this article, resuscitation topics are
      discussed and recommendation offered.

PMID- 9523072
TI  - Surfactant. Evolving issues.
AB  - Understanding surfactant composition, function, and therapeutic usefulness has
      increased exponentially over the last 40 years. This article reviews the history
      and current understanding of surfactants, composition and comparisons of
      surfactants, method and timing of surfactant administration, dosage and
      retreatments, and the use of surfactants in conditions other than respiratory
      distress syndrome.

PMID- 9523073
TI  - Ventilatory management in neonates. Science or art?
AB  - Conventional mechanical ventilation continues to be the standard mode of support
      for neonates with respiratory failure. Controversies regarding the selection of
      optimal ventilatory strategies still abound. A deep understanding of physiologic
      concepts as well as a critical appraisal of the literature is needed to optimize
      the ventilatory management of the newborn. Principles of gas exchange, pulmonary
      mechanics and control of breathing are reviewed in the context of their relevance
      during mechanical ventilation. The application of these concepts to the
      ventilatory strategies for the management of infants with respiratory distress is
      presented, and current controversies are emphasized.

PMID- 9523074
TI  - Controversies in patient-triggered ventilation.
AB  - Patient-triggered ventilation is a relatively recent development in neonatal
      mechanical ventilation. Advances in microprocessor-based technology, transducers,
      and monitoring have enabled patient-driven ventilator control and synchronization
      of mechanical ventilation with patient effort. The novelty of the newer
      ventilatory techniques has generated several controversies that remain to be
      resolved. Among these are signal detection and transduction, the optimal
      ventilatory modes, and weaning during patient-triggered ventilation.

PMID- 9523075
TI  - The use of sedation and muscle relaxation in the ventilated infant.
AB  - The use of sedation, muscle relaxation, or analgesia in the management of
      ventilated neonates has been controversial. Many neonatologists face a difficult
      decision on whether or not to use a muscle relaxant on a ventilated infant. This
      article reviews neonatal physiology and pharmacology, drug administration,
      absorption, distribution, and certain selected sedatives and analgesics. The
      muscle relaxants, financial issues, and family issues are also discussed.

PMID- 9523076
TI  - Issues in the nutritional support of the ventilated baby.
AB  - Extremely low birth weight (ELBW) premature infants who populate intensive care
      nurseries today often receive such overriding attention to their acute
      respiratory illness that appropriate attention to certain other adjunctive needs;
      adequate nutrition is often delayed. The outcome for these ELBW infants may be
      influenced by the intensity and length of the period of less-than-adequate
      nutrition. This article discusses initial fluid therapy, early postnatal
      intravenous amino acid administration, choice of energy substrate, and initiation
      and advancement of enteral feedings.

PMID- 9523077
TI  - Transfusion practices in infants receiving assisted ventilation.
AB  - Controversies about medical practices usually arise from lack of definitive
      scientific studies. In the presence of continuing controversy about the
      appropriate hemoglobin level for ventilated (or nonventilated) infants, we can
      attempt to derive as much useful information as possible. In this article, the
      authors focus on four subjects: the physiologic role of red cells, the clinical
      effects of anemia and the proposed clinical benefit of red cell transfusions in
      preterm infants, the risks associated with transfusions, and the use of
      recombinant erythropoietin as an alternative to transfusion therapy.

PMID- 9523078
TI  - Controversies in high-frequency ventilation.
AB  - Clinical care of newborns with respiratory failure is constantly changing and
      improving. Thus, optimizing health care is a commitment to constant, but careful
      change. This article addresses five current controversies about high-frequency
      ventilation and provides a discussion on each debated question.

PMID- 9523079
TI  - Extracorporeal membrane oxygenation. Controversies in selection of patients and
      management.
AB  - This article reviews controversies associated with the selection of patients for
      extracorporeal membrane oxygenation (ECMO) and their management. Although there
      has been a raging debate regarding the use of ECMO in the management of hypoxic
      respiratory failure in the near-term and term newborn, the authors maintain that
      this issue is resolved and that ECMO is now a standard of care and should be
      offered to every neonate who is likely to fail conventional treatment. It is the
      authors' contention, that there is no apparent increase in morbidity associated
      with the use of ECMO and that better results might be achieved if ECMO were
      employed earlier in the patient's course, before hypoxic-ischemia organ damage
      occurs.

PMID- 9523080
TI  - Is liquid ventilation a reasonable alternative?
AB  - Liquid breathing has been in medical literature for nearly 80 years and has been
      proposed as a means of improving gas exchange in critically ill infants since the
      1970s. Extensive laboratory experience with perfluorochemical liquid ventilation
      has lead to clinical trials in infants, children, and adults. This article
      discusses the process and physiologic response to liquid breathing in neonates,
      and reviews some of the factors that need clarification prior to approval as a
      routine clinical therapy.

PMID- 9523081
TI  - Volutrauma, PaCO2 levels, and neurodevelopmental sequelae following assisted
      ventilation.
AB  - Today it is essential that we define care practices in neonatology that not only
      increase survival but also produce optimal pulmonary and neurodevelopmental
      outcomes for our patients. Assisted ventilatory care continues to be influential
      at all three levels. In this article, the authors discuss current understanding
      of the possible mechanisms for pulmonary and neurologic injury, or benefits
      associated with ventilation at both low and high PaCO2 levels, as well as
      evidence for neurodevelopmental sequelae with various ventilator strategies.

PMID- 9523082
TI  - Treatment of bronchopulmonary dysplasia. A review.
AB  - Bronchopulmonary dysplasia (BPD), first described in 1966, remains an issue of
      both clinical and public health importance. BPD may be associated with chronic
      respiratory difficulties, prolonged and recurrent hospitalization, an increased
      incidence of neurodevelopmental disabilities, growth restriction, and death.
      Controversies regarding the cause of BPD are important to resolve in an attempt
      to develop strategies for prevention.

PMID- 9523083
TI  - Controversies in the use of inhaled nitric oxide therapy in the newborn.
AB  - Inhaled nitric oxide (NO) causes sustained improvement in oxygenation in near
      term and term newborns with persistent pulmonary hypertension of the newborn
      (PPHN), and reduces the need for extracorporeal membrane oxygenation (ECMO).
      However, many questions remain concerning the application of inhaled NO to less
      severely ill infants, its use in units without immediate access to adjuvant
      therapies for hypoxemic respiratory failure, and in centers without ECMO.
      Particular vigilance must be given to the potential impact of widespread
      dissemination on inhaled NO therapy on time ECMO initiation, and the
      inappropriate use of inhaled NO in premature neonates.

PMID- 9523084
TI  - Contemporary controversies in the management of congenital diaphragmatic hernia.
AB  - Congenital diaphragmatic hernia (CDH) has remained the most frustrating of the
      major birth defects to manage successfully. Despite the earlier detection of
      severe diaphragmatic defects by prenatal ultrasound, and the early recognition of
      CDH as a cause for respiratory distress presenting at birth, current mortality
      has improved little from the original series presented in 1940 by Ladd and Gross.
      This article discusses the difficulty in defining population with congenital
      diaphragmatic hernia, current controversies in the medical and surgical
      management of these patients, appropriate timing and usage of ECMO, a review of
      current, experimental therapies, and short-term and long-term outcomes of these
      patients.

PMID- 9523085
TI  - Ceramic drug-delivery devices.
AB  - A variety of ceramics and delivery systems have been used to deliver chemicals,
      biologicals, and drugs at various rates for desired periods of time from
      different sites of implantation. In vitro and in vivo studies have shown that
      ceramics can successfully be used as drug-delivery devices. Matrices, inserts,
      reservoirs, cements, and particles have been used to deliver a large variety of
      therapeutic agents such as antibiotics, anticancer drugs, anticoagulants,
      analgesics, growth factors, hormones, steroids, and vaccines. In this article,
      the advantages and disadvantages of conventional drug-delivery systems and the
      different approaches used to deliver chemical and biological agents by means of
      ceramic systems will be reviewed.

PMID- 9523086
TI  - The interaction of liposomes with the complement system.
AB  - Activation of complement (C) by haptenized liposomes has been utilized for a long
      time to study the interaction of biological membranes with C proteins, or as a
      sensitive immunoassay for the measurement of specific antigens, antibodies, or
      serum hemolytic C levels. However, it has been increasingly recognized that
      regardless of antigenicity, C activation is an intrinsic property of all charged
      phospholipid/cholesterol bilayers. Liposome-induced C activation and its
      biological consequences show significant interspecies and interindividual
      variation, and critically depend on the properties of vesicles as well.
      Activation can proceed through both the classical and the alternative pathways,
      with or without the involvement of antibodies. The practical significance of the
      phenomenon is twofold: 1) opsonization of the vesicles promotes their clearance
      from the circulation and 2) the liberation of C3a and C5a can cause numerous,
      potentially adverse, biological reactions. In fact, many cardiovascular and
      hematological changes observed following administration of liposomes in vivo can
      be explained by C activation; a fact that has not yet gained wide recognition in
      the field of drug-carrier liposomes.

PMID- 9523088
TI  - Anterior chamber angle biometry: quadrant variation, age change and sex
      difference.
AB  - PURPOSE: To estimate the anterior change angle width (ACAW) in healthy volunteers
      quantitatively using an anterior eye segment analysis system and to clarify the
      involvement of aging and sex in ACAW. METHODS: The ACAW of the upper, lower,
      medial, and lateral quadrants of 42 eyes from 42 healthy volunteers was measured
      by the NIDEK EAS-1000 anterior eye segment analysis system, a non-invasive in
      vivo measuring method based on Scheimpflug image analysis. Data from all subjects
      were employed to investigate aging and quadrant differences; and age-matched male
      and female subjects were chosen from all subjects to study sex difference and
      aging. RESULTS: Young subjects showed no significant inter-quadrant differences
      of ACAW. However, ACAW showed a significant negative correlation with age in all
      quadrants, but the lateral quadrant showed much more narrowing than the others.
      The age-matched study revealed that ACAW narrowing was much greater in females
      than in males, and a polynomial regression analysis showed that this sex
      difference appeared in subjects older than middle age. CONCLUSIONS: The anterior
      eye segment analysis system revealed that ACAW decreased with age, especially in
      the lateral quadrant. The significantly more marked narrowness of ACAW in females
      older than middle age may be related to the high incidence of angle closure
      glaucoma in elderly females.

PMID- 9523087
TI  - Measurement of oxygen production by in vitro human and animal lenses with an
      oxygen electrode.
AB  - PURPOSE: This paper describes an advantageous method of measuring the activity of
      the enzyme catalase, which has an important antioxidative role in the lens. This
      method allows the measurement of catalase in whole lenses. METHODS: Exposure to
      UVA (99% UV-A) radiation was used to stress animal and human (Eye Bank) lenses in
      vitro. The ability of lens catalase to convert H2O2 into O2 was measured
      directly, using an oxygen electrode and meter. This method is very specific, as
      catalase is the only enzyme that converts H2O2 to O2. RESULTS: Catalase in the
      lenses of humans, rabbits, and squirrels catalyzed the production of O2 from H2O2
      very efficiently. The anterior equatorial regions of these lenses were the most
      active O2 producing areas. More than 95% of lens catalase activity was found in
      the capsule-epithelium layer. Exposure to UVA radiation, up to approximately 100
      J/cm2 in 18 h, strongly inhibited O2 production from 0.77 mM H2O2 by the lenses.
      Catalase activity decreased with increasing age. Mixed cataractous human lenses
      produced O2 from H2O2 at only 60% of the rate of normal lenses of similar ages.
      Nuclear cataracts produced O2 at only 75% of the rate of normal lenses. Alpha
      tocopherol (10(-5) M) protected lens catalase activity strongly. Alpha-tocopherol
      is known to accumulate in and protect against cell membrane peroxidation, and
      against singlet oxygen formation. These oxidative mechanisms appear to contribute
      to catalase photoinactivation. CONCLUSIONS: The method described indicated that
      catalase is a crucial antioxidative enzyme in the normal lens. Its inactivation
      could upset the oxidation-reduction balance in the lens and stimulate lens
      opacification.

PMID- 9523089
TI  - Beta adrenergic antagonist permeation across cultured rabbit corneal epithelial
      cells grown on permeable supports.
AB  - PURPOSE: To determine whether cultured rabbit corneal epithelial cells (RCEC),
      grown on permeable supports, provide a suitable in vivo model for characterizing
      transcellular drug permeation and metabolism. METHODS: Primary rabbit corneal
      epithelial cells grown in DMEM-F12 were seeded on Transwell-COL inserts coated
      with fibronectin. The epithelial barrier integrity was evaluated, based on
      measurements of 14C-mannitol and 3H-PEG900, and their transepithelial electrical
      resistance (TEER). Ultrastructure evaluation was based on scanning electron
      microscopy and transmission electron microscopy, which were performed 8 days
      after seeding. Measurements of beta adrenergic antagonist permeability were
      performed to assess transcellular permeability. RESULTS: Eight days after
      seeding, the TEER reached a peak of 144 omega.cm2 and the 14C-mannitol and 3H
      PEG900 permeabilities were 6.8 x 10(-6) and 2.9 x 10(-6) cm/sec, respectively.
      Ultrastructural analysis revealed a multilayered structure with numerous
      microplicae and typical cytoplasmic organelles along with desmosomes. The
      relationship between permeation of beta-blockers and lipophilicity resembled the
      intact isolated cornea. CONCLUSIONS: This is the first description of cultured
      RCEC grown on permeable support. Many of its properties mimic those described in
      the intact corneal epithelium. Even though its electrical tightness is less than
      that of the intact cornea, the transcellular permeability to lipophilic beta
      antagonists is comparable to the isolated preparation. Therefore, this model will
      facilitate characterization of ocular permeation mechanisms of hydrophobic drugs
      whose route of permeation is transcellular.

PMID- 9523090
TI  - Matrix metalloproteinases and metalloproteinase inhibitors in human
      interphotoreceptor matrix and vitreous.
AB  - PURPOSE: We wished to establish which matrix metalloproteinases (MMPs) and
      metalloproteinase inhibitors (TIMPs) were present in human interphotoreceptor
      matrix (IPM) and vitreous. METHODS: IPM and vitreous were obtained from
      postmortem human eyebank eyes. Western immunoblots were probed with antibodies
      against human MMPs and TIMPs. Assays specific for elastase activity were also
      performed. RESULTS: Immunoblot analysis indicated the presence of MMP-1
      (interstitial collagenase), MMP-2 and MMP-9 (gelatinases A and B), MMP-3
      (stromelysin-1) and TIMP-1, -2 and -3 in both IPM and vitreous. MMP-7
      (matrilysin) and MMP-12 (metalloelastase) were not found in either IPM or
      vitreous. CONCLUSIONS: This is the first demonstration of the MMPs and TIMPs in
      human IPM and of the TIMPs in human vitreous. While these enzymes are most likely
      involved in normal turnover within the extracellular matrices that surround the
      neural retina, they may also play a role in a number of retinal diseases,
      particularly proliferative diabetic retinopathy and age-related macular
      degeneration.

PMID- 9523091
TI  - Cytidine-5'-diphosphocholine improves visual acuity, contrast sensitivity and
      visually-evoked potentials of amblyopic subjects.
AB  - PURPOSE: Cytidine-5'-diphosphocholine (CDP-choline) therapy is currently used to
      improve the consciousness level in patients with brain lesions and as a
      complement to levodopa therapy in Parkinson's disease. Recently, the substance
      has been shown to improve the visual acuity (VA) of both eyes of adults with
      amblyopia. This study aims at establishing whether Contrast Sensitivity (CS) and
      visually-evoked potentials (VEPs) also change after CDP-choline treatment.
      METHODS: VA, CS, and VEPs were measured in a group of amblyopic volunteers (n =
      10, mean age 24.8 years) before treatment with Neuroton (CDP-choline, 1 g/day
      intramuscularly [IM] for 15 days) and the day after termination of the same. CS
      was evaluated, using a forced-choice, automatic procedure (QUEST: Watson and
      Pelli, 1983). Steady-state VEPs were recorded in response to counterphased (8 Hz)
      sinusoidal gratings (2 c/deg) of different contrasts. RESULTS: On average, after
      treatment, VA improved 1.4-1.5 lines in the amblyopic eyes and 0.4 lines in the
      normal eyes. CSs improved in both dominant and amblyopic eyes by about 3 dB. VEPs
      increased in amplitude (about 30%) and advanced in phase (about 0.2 pi rad).
      Amplitude and phase changes were not correlated. CONCLUSIONS: Treating adult
      amblyopes with CDP-choline has the effect of improving their VA, CS and VEPs.
      Changes occur in both eyes, although to different extents, and resemble those
      previously reported for levodopa treatment.

PMID- 9523092
TI  - Morin hydrate: a better protector than purpurogallin of corneal endothelial cell
      damage induced by xanthine oxidase and SIN-1.
AB  - PURPOSE: Free radicals are responsible for tissue injury in corneal preservation
      and transplantation. Morin hydrate, a flavonoid from Brazil wood, has been shown
      to be cytoprotective in several types of cells. The aim of this study was to
      investigate the effectiveness of morin hydrate on rabbit corneal endothelial
      cells against damage induced by oxyradicals and nitric oxide. METHODS: Corneal
      endothelial cell cultures were prepared from New Zealand white rabbits, using
      standard microcarrier technique. Two free-radical-generating systems were used-17
      IU/L xanthine oxidase/1 mM hypoxanthine and 5 mM 3-morpholinosydnonimine-N
      ethylcarbamide (SIN-1, a nitric oxide-donating agent). RESULTS: Over 95% of
      cultured corneal endothelial cells necrosed within 3.6 +/- 1.5 min after exposure
      to xanthine oxidase/hypoxanthine. Adding morin hydrate delayed cell necrosis to
      5.8 +/- 0.3 min (0.25 mM morin hydrate), 13.3 +/- 5.0 min (0.5 mM), and 41.5 +/-
      8.6 min (1.0 mM). Exposed to nitric oxide generated by SIN-1, cells necrosed by
      9.5 +/- 2.5 min, versus 14.1 +/- 1.3 min (0.25 mM morin hydrate), 27.2 +/- 2.0
      min (0.5 mM), and 43.3 +/- 5.4 min (1.0 mM). Morin hydrate significantly
      prolonged survival of cells compared to equimolar concentrations of
      purpurogallin, Trolox, or ascorbate (P < 0.01). CONCLUSION: This study
      demonstrates that morin hydrate behaves as a broad-spectrum antioxidant: it
      scavenges not only xanthine oxidase/hypoxanthine-generated oxyradicals, but also
      nonenzymatic, nitrogen-derived radicals, better than those above mentioned
      antioxidants. This property of morin hydrate may help prevent free radical damage
      in corneal preservation solutions.

PMID- 9523093
TI  - Probing cataractogenesis associated with mevalonic aciduria.
AB  - PURPOSE: Mevalonic aciduria in humans results from a genetic deficiency of
      mevalonate kinase and is characterized by very high plasma mevalonic acid levels,
      developmental malformations and cataracts. This study tested the possibility that
      the cataracts could result from direct toxicity of the accumulated mevalonate.
      METHODS: Young rat lenses were cultured for up to 4 days in medium TC199
      containing 1 to 5 mM mevalonic acid. Changes in the water, sodium and potassium
      content of the lens were followed; electrolytes were measured by atomic
      absorption spectroscopy. The identities of proteins leaked from the lens were
      determined by sodium dodecylsulfate polyacrylamide electrophoresis and
      isoelectric focusing. Changes in cation flux were measured by 86Rb uptake. Lens
      concentrations of mevalonic acid were measured from uptake of 3H-mevalonolactone.
      RESULTS: Culture of young rat lenses with 3 to 5 mM mevalonic acid produced lens
      opacification and nuclear cataracts starting within 1 to 2 days of culture.
      Mevalonic acid did not concentrate in the lens. Treated lenses accumulated water
      and sodium and lost potassium and soluble gamma crystallin proteins. These
      changes were preceded by a loss of the len's capacity to concentrate 86Rb, a
      potassium analogue. The loss of 86Rb uptake might have been due to a slow
      poisoning of the cation pump, direct effects on membrane integrity or both.
      CONCLUSIONS: The results show that chronic exposure of the lens to mevalonic acid
      can induce cataracts, which appear caused by a progressive increase in the
      permeability of lens cell membranes. The cataracts associated with mevalonic
      aciduria could be due to toxicity from mevalonic acid.

PMID- 9523094
TI  - Saccade-vergence trajectories under free- and instrument-space environments.
AB  - PURPOSE: The purpose of this study was to examine in detail the binocular
      fixation top-view trajectories of saccade-vergence responses to asymmetrical
      targets, and to compare latency difference between saccade and vergence, under
      the free- and instrument-space viewing environments. METHODS: Binocular eye
      movements were recorded using the infrared reflection technique in five visually
      normal subjects. Responses were obtained for various asymmetrical target
      positions under both free- and instrument-space environments. RESULTS: Four types
      of top-view trajectories that represented normal variations in saccade and
      vergence control were found: straight, overshoot, undershoot, and saccade
      vergence. Also, it was found that under the instrument-space environment, there
      was a predominance of saccade-vergence trajectories and a scarcity of overshoot
      trajectories, whereas under the free-space environment, there was a predominance
      of overshoot trajectories, and a scarcity of saccade-vergence trajectories.
      Further, under the instrument-space environment, latency was significantly longer
      for saccade than vergence (35.9 +/- 15.7 msec; t = 5.1, degrees of freedom (df) =
      4, P < 0.01), whereas under the free-space environment, there was no latency
      difference (-10.5 +/- 14.8 msec; = -1.6, df = 4, P > 0.05). CONCLUSIONS: The
      differences in response profiles under the two viewing environments could be
      accounted for by differences in timing of saccade and vergence onset. Moreover,
      in contrast to some recent investigations that suggest higher center control of
      individual trajectories, which was dependent on the naturalistic scene, these
      trajectories could be accounted for by known neural and oculomotor mechanisms,
      with the higher centers using a priori information about spatial location of the
      target, to assist in the synchrony of saccade and vergence onset under the free
      space environment.

PMID- 9523095
TI  - Uveal melanomas contain antigenically specific and non-specific infiltrating
      lymphocytes.
AB  - PURPOSE: Tumor-infiltrating lymphocytes (TIL) were recovered from a series of
      human choroidal melanomas and expanded in cultures containing interleukin-2 (IL
      2) to determine whether TIL contained cytotoxic cells that could be activated in
      vitro. METHODS: TIL were recovered from six ocular melanoma patients and expanded
      in vitro with IL-2. Cytotoxic activity was tested in a standard 4-hr 51Cr release
      assay. The HLA class I phenotype of patients was determined, using peripheral
      blood lymphocytes and the Amos modified-cytotoxicity test. HLA class I expression
      on tumor cells was determined by flow cytometry. RESULTS: TIL from four patients
      lysed autologous ocular melanoma cells. Two of these patients possessed TIL that
      displayed specific cytotoxic activity and failed to lyse tumor cells from other
      patients (HLA-mismatched, or -matched). TIL from the remaining two patients
      possessed non-specific cytotoxic cells that lysed ocular melanoma cells from a
      variety of other patients (HLA-mismatched). TIL from patients that failed to lyse
      autologous tumor cells possessed cytotoxic activity for ocular melanoma cells
      from other HLA-mismatched patients. CONCLUSIONS: Ocular melanomas accumulate
      lymphocytes with the potential to kill tumor cells. Our results imply that
      elimination of tumor cells may be possible by activation of cytotoxic cells
      present within progressively growing ocular tumors.

PMID- 9523096
TI  - Gelatinase concentration in tears of corneal-grafted patients.
AB  - PURPOSE: Gelatinolytic enzymes, which degrade type IV basement membrane collagen,
      have been shown to be expressed by corneal cells, either constitutively
      (gelatinase A or MMP-2) or after induction (gelatinase B or MMP-9). Our aim was
      to determine whether an enhanced MMP-9 and eventually MMP-2 concentration in
      tears could be evidenced in the case of corneal-graft failure. METHODS: The
      amount of MMP-2 and MMP-9 gelatinolytic enzymes was measured by quantitative
      zymography in tears of twenty-one controls (84 samplings) and in tears of twenty
      three corneal-grafted patients in a one-year post-graft follow-up study. RESULTS:
      The mean MMP-2 values in controls were of 8.4 (+/-7.3) pg/10 micrograms protein
      and the mean MMP-9 values in controls were of 73 (+/-76) pg/10 micrograms
      protein. No active gelatinase form was detected in any of controls, but in all
      cases of corneal graft failure, the active forms of both enzymes were present,
      and enzyme concentrations were higher than control values. All patients had
      significantly higher MMP-9 values than controls at each sampling time (p <
      0.0001). The "corneal-graft failure" patient group had statistically significant
      higher MMP-9 concentrations in tears than the "successful-graft" patient group at
      one month (p = 0.0312), four months (p = 0.0158) and one year (p < 0.01) after
      the graft. The presence of active MMP-9 was highly significant of graft failure
      four months and one year after the graft (p < 0.0001). In contrast, MMP-2
      increase was delayed, with significantly higher MMP-2 values than controls in all
      patients at four months (p = 0.0231) and one year (p = 0.0001) after the graft,
      but MMP-2 values could not discriminate between patient groups. CONCLUSIONS: In
      our study, all cases of graft failure showed abnormally high levels of the active
      forms of metalloproteinase enzymes, and these values far exceeded the maximum
      control concentration. MMP-9 measurements in tears made between one and four
      months after corneal transplantation, and while local corticotherapy is steadily
      established, should help in predicting corneal graft rejection.

PMID- 9523097
TI  - Tear changes in contact lens wearers following overnight eye closure.
AB  - PURPOSE: Tear protein composition alters during eye closure, by becoming rich in
      secretory IgA (sIgA) and certain complement proteins. This may reflect altered
      ocular defense mechanisms during eye closure. Since overnight wear of contact
      lenses (CLs) is associated with an increased risk of corneal infection and
      inflammation, this study aimed to quantify tear protein changes with overnight
      soft CL wear. METHODS: Non-stimulated tears were collected from 9 CL wearers
      prior to CL wear (baseline), after daily CL wear, and after 8 h sleep. Lenses
      were removed following wear and were extracted in 80% urea at 95 degrees C.
      Secretory IgA, complement C3 and C4, were measured using ELISA and total protein
      using the Pierce BCA assay. Assays were performed on tear samples and CL
      extracts. RESULTS: Baseline tear protein concentrations were: 0 total tear
      protein (9.37 +/- 2.97 mg/mL), C3 (4.4 +/- 2.1 micrograms/mL), C4 (0.1 +/- 0.1
      micrograms/mL), and sIgA (0.84 +/- 0.34 mg/mL). There were no differences in any
      protein levels between daily CL wear and no CL wear (p > 0.05). Following sleep,
      protein concentrations were: total tear protein (43.64 +/- 24.30 mg/mL), C3 (72.5
      +/- 49.9 micrograms/mL), C4 (6.7 +/- 5.2 micrograms/mL), and sIgA (5.53 +/- 5.15
      mg/mL). Total protein extracted from CLs after daily wear was 90 +/- 27
      micrograms/CL and, after overnight wear, 152 +/- 24 micrograms/CL. Negligible
      levels of C3, C4 and sIgA were recovered from CL extracts. CONCLUSIONS:
      Uncomplicated daily use of soft CLs does not appear to alter certain tear
      proteins compared with baseline levels. Uptake of these proteins by the CL does
      not appear to deplete the tear protein levels. Overnight levels of all tear
      proteins were increased, compared to daily CL wear.

PMID- 9523098
TI  - Endothelium-dependent vasodilation in the uvea of hypertensive and normotensive
      rats.
AB  - PURPOSE: The effects of endothelium-related substances such as acetylcholine, a
      stimulator of endogenous NO-production, the NO-synthesis inhibitor L-NMMA, the
      exogenous NO-donor sodium nitroprusside and the endothelin (ET)A-receptor
      antagonist BQ123, on uveal blood flow were investigated in normotensive and
      hypertensive SHR rats. METHOD: The radioactively-labelled microsphere method was
      applied for the measurement of regional blood flow in the uvea. RESULTS: Under
      resting conditions, local blood flow was lower in the hypertensive animals. The
      increase in choroidal blood flow (145 +/- 50%; P < 0.01) and reduction in
      vascular resistance (-58 +/- 7%; P < 0.01) observed in the WKY after i.v.
      infusion of acetylcholine, 2 micrograms x kg bw-1 x min-1, were significantly
      less pronounced in animals pretreated with L-NMMA, indicating local formation of
      NO as a vasodilator mechanism. In contrast, acetylcholine did not induce
      significant vasodilation in the choroid of SHR rats. In the anterior uvea of both
      strains, acetylcholine did not affect local blood flow. L-NMMA, 20 mg x kg bw-1,
      alone reduced blood flow in the entire uvea of both strains. Intravenous
      injection of BQ123, 1 mg x kg bw-1, did not affect regional blood flow in the
      uvea of WKY or SHR animals. Infusion of acetylcholine following ETA-receptor
      blockade induced vasodilation in both the choroid and anterior uvea in the WKY
      but not in the SHR. CONCLUSIONS: Acetylcholine-stimulated NO-mediated
      vasodilation, but not basal NO-formation, was impaired in the choroid of the SHR.
      Furthermore, an interaction between vasoconstricting ET and acetylcholine was
      found in the anterior uvea of normotensive but not hypertensive rats.

PMID- 9523099
TI  - Calcitonin gene-related peptide relaxes rabbit iris dilator smooth muscle via
      cyclic AMP-dependent mechanisms: cross-talk between the sensory and sympathetic
      nervous systems.
AB  - PURPOSE: The purpose of these studies is to determine whether or not cyclic AMP
      is involved in the relaxant action of calcitonin gene-related peptide (CGRP) in
      rabbit iris dilator muscle. METHODS: Iris dilator muscle isolated from rabbit was
      used. Accumulation of cAMP and cGMP in the tissue extracts was measured by
      radioimmunoassay (RIA), IP3 production was measured by ion-exchange
      chromatography, and changes in tension were recorded isometrically. RESULTS:
      CGRP, vasoactive intestinal peptide, prostaglandin E2, isoproterenol and
      forskolin (1 microM of each) increased cAMP accumulation by 136, 256, 78, 141 and
      315%, respectively. CGRP dose-dependently increased cAMP accumulation (EC50 =
      5.25 nM), inhibited IP3 production (EC50 = 5.4 nM) and induced relaxation (EC50 =
      10 nM) in muscle precontracted with norepinephrine (NE) (10 microM).
      Prostaglandin E2, isoproterenol and forskolin also induced relaxation. CGRP
      stimulated cAMP formation either in the presence or absence of 3-isobutyl-1
      methylxanthine (IBMX), a cAMP phosphodiesterase inhibitor, in a time- and
      concentration-dependent manner. The neuropeptide had no effect on cGMP
      accumulation. CGRP (8-37), a CGRP receptor antagonist, reversed the relaxant
      action of the neuropeptide and inhibited CGRP-induced cAMP accumulation in a
      concentration-dependent manner (IC50 = 12.5 nM). 2',5'-dideoxyadenosine (DDA), a
      specific adenylate cyclase inhibitor, significantly reduced the inhibitory
      actions of CGRP on NE-induced contraction and IP3 production and inhibited CGRP
      induced cAMP accumulation in a concentration-dependent manner (IC50 = 6.9 nM).
      CONCLUSIONS: These results strongly suggest that cAMP mediates the relaxant
      action of CGRP in rabbit iris dilator. The mechanism of cAMP inhibition of NE
      induced IP3 production and contraction is unclear. Modulation of alpha 1
      adrenergic function in the iris dilator by CGRP-induced cAMP formation is yet
      another example of cross-talk between the cAMP and IP3-Ca2+ second messenger
      systems, it demonstrates a cross-talk between the sympathetic and sensory nervous
      systems. CGRP-containing sensory nerve fibers could play an important role in
      regulation of smooth muscle function in the iris-ciliary body.

PMID- 9523100
TI  - Inflammatory reaction via arachidonic acid cascade after intravitreal injection
      of endothelin-1.
AB  - PURPOSE: To investigate the characteristics of anterior chamber inflammatory
      reaction induced by intravitreal injection of endothelin-1 (ET-1). METHODS: The
      time course of changes in aqueous protein concentration (APC) after intravitreal
      injection of 10(-4), 10(-5), 10(-6) and 10(-7) M ET-1 into rabbit eyes was
      measured with a laser flare-cell meter. The influence of a topical diclofenac
      sodium (DFNa) pre- and post-treatment was assessed. Aqueous prostaglandin E2 and
      leukotriene B4 concentration was quantified using a radioimmunoassay technique.
      RESULTS: Intravitreal injection of 10(-4) and 10(-5) M ET-1 significantly
      increased APC, while 10(-6) and 10(-7) M ET-1 did not induce anterior chamber
      inflammation. After 10(-5) M ET-1 injection, APC reached a maximum at 4 h post
      treatment and returned to a normal level 48 h after injection. Eyes treated with
      10(-4) M ET-1 displayed a bi-phasic time course, with peak values observed 4 to 8
      h as well as 48 h after administration. Pre- and post-treatment with topical DFNa
      completely suppressed the APC increase in the 10(-5) M ET-1 preparation, and
      considerably inhibited it in the 10(-4) M ET-1 preparation. After ET-1 injection,
      aqueous prostaglandin E2 concentration increased significantly, followed by an
      increase in APC. There were no changes in leukotriene B4 concentration.
      CONCLUSIONS: ET-1 induces anterior chamber inflammation via the cyclooxygenase
      pathway of the arachidonic acid cascade. The lipoxygenase pathway is not involved
      in this reaction.

PMID- 9523101
TI  - Effects of ascorbic acid on levels of fibronectin, laminin and collagen type 1 in
      bovine trabecular meshwork in organ culture.
AB  - PURPOSE: Fibronectin, laminin and collagen type I are important extracellular
      matrix products of trabecular meshwork cells. This study was performed to examine
      the effects of ascorbic acid, a significant component in the aqueous humor, on
      the levels of these proteins in trabecular meshwork cells maintained in organ
      culture. METHODS: The anterior segment of freshly enucleated bovine eyes was
      perfused in a modified organ culture system. Three cultures were set up
      simultaneously. One received serum-free medium containing 100 micrograms/ml of
      ascorbic acid, one received 250 micrograms/ml of ascorbic acid and one served as
      a control. After 72 h, the tissues were processed for paraffin sections and
      immunostaining was conducted using an avidin-biotin-peroxidase complex method.
      Western blot and dot blot assays were performed on tissue extracts. RESULTS:
      Compared with the controls, the staining for fibronectin and laminin was markedly
      enhanced in trabecular meshwork tissues treated with both concentrations of
      ascorbic acid. Increased collagen type I production by trabecular meshwork cells
      was also demonstrated in the presence of ascorbic acid. Western blot and dot blot
      results confirmed the immunostaining findings. CONCLUSIONS: Ascorbic acid
      promotes production of fibronectin, laminin and collagen type I by trabecular
      meshwork cells. The organ culture results are consistent with those obtained
      previously from tissue culture studies.

PMID- 9523103
TI  - Innate immunity antigen recognition. Web alert.

PMID- 9523102
TI  - The vitreous protein concentration is increased prior to neovascularization in
      experimental ROP.
AB  - PURPOSE: To test the hypothesis that the vitreous protein content is altered
      prior to the development of neovascularization in an experimental model of
      retinopathy of prematurity (ROP). METHODS: Newborn rats underwent either a
      variable oxygen exposure or room air exposure following birth. On day 13 or 14,
      two days prior to neovascularization, the steady state vitreous and plasma total
      protein levels in room-air controls or variable-oxygen-exposed newborn rats were
      determined; similar measurements were also made for control adult rats. RESULTS:
      There was a significant difference (P < 0.05, 2-tailed t-test) in the vitreous
      protein concentration between the age-matched control and experimental newborn
      rats. The protein level in the ROP rat plasma was not significantly (P > 0.05)
      different from that in the age-matched control animals. The vitreous-to-plasma
      protein ratios of both the control and ROP newborn animals were significantly
      greater (P < 0.05) than that in the adults. CONCLUSIONS: The results of this
      study demonstrate, for the first time, increased vitreous protein levels prior to
      the development of neovascularization in the newborn rat model of ROP. In
      addition, developmental changes in vitreous protein levels were identified. The
      role of developmental and pathologic alterations in the blood-ocular barriers in
      this study is discussed.

PMID- 9523104
TI  - An ancient system of host defense.
AB  - Research over the past few years has begun to provide significant advances in our
      understanding of the interplay between the innate and adaptive immune systems.
      New findings in several model systems reveal remarkable parallels and
      conservation of ancient host defense pathways in organisms separated by over a
      billion years of evolution.

PMID- 9523105
TI  - Antimicrobial proteins in induced plant defense.
AB  - During the past few years a wide spectrum of plant antimicrobial proteins has
      been detailed, and enhanced resistance has been obtained by introducing the
      corresponding genes into crop species to produce transgenic lines. With the aim
      of manipulating the plant signals that regulate an array of defense responses,
      the most intense research focuses on the avr-R-mediated recognition events and
      elucidation of the subsequent signaling pathways that govern the activation of
      genes encoding antimicrobial proteins.

PMID- 9523106
TI  - Role of the prophenoloxidase-activating system in invertebrate immunity.
AB  - The melanization reaction, which is a common response to parasite entry in
      invertebrate animals, especially arthropods, is due to the activity of an
      oxidoreductase, phenoloxidase. This enzyme is part of a complex system of
      proteinases, pattern recognition proteins and proteinase inhibitors constituting
      the so-called prophenoloxidase-activating system. It is proposed to be a non-self
      recognition system because conversion of prophenoloxidase to active enzyme can be
      brought about by minuscule amounts of molecules such as lipopolysaccharide,
      peptidoglycan and beta-1, 3-glucans from micro-organisms. Several components of
      this system recently have been isolated and their structure determined.

PMID- 9523107
TI  - Complement-related serine proteases in tunicates and vertebrates.
AB  - Serum mannose-binding lectin binds to pathogens in association with a serine
      protease termed MASP, and in this form, plays a crucial role in innate immunity
      by activating complement in a manner similar to activation via the classical
      pathway. MASP, C1r and C1s belong to the same family of serine proteases. In
      addition to its presence in advanced species, MASP also exists in primitive life
      forms such as tunicates and may be an evolutionary prototype of this family.

PMID- 9523108
TI  - Linkages of innate and adaptive immunity.
AB  - The innate immune system is activated by pathogens or environmental antigens
      following their binding by recognition molecules such as mannan-binding lectin, C
      reactive protein and the mannose receptor. Natural antibody, which represents a
      collection of germline-encoded antigen recognition molecules, is also important
      in recognition of pathogens and activation of the innate immune system via the
      classical pathway of complement activation. The major source of natural antibody
      is CD5+ B-1 cells which differ from conventional B cells (B-2 cells) firstly
      because they are thought to require contact with antigen for expansion and
      maintenance and secondly because in general they do not appear to undergo somatic
      hypermutation. We review results which support an important role for complement
      in maintenance of B-1 cells, the effect being mediated by B cell expression of
      complement receptors CD21 and CD35. We propose that complement and natural
      antibody are interdependent: clonal selection and expansion of CD5+ B-1 cells is
      dependent on contact with antigen coated by the complement component C3d, while
      efficient recognition of pathogens and activation of complement is dependent in a
      large part on natural antibody. This hypothesis is supported by the finding that
      mice deficient in CD21 and CD35 have a reduced number of CD5+ B-1 cells and are
      missing specificities for certain antigens commonly found in wild-type mice, such
      as lipopolysaccharide, Escherichia coli surface antigens and neoepitopes
      expressed on hypoxic intestinal endothelium.

PMID- 9523111
TI  - The mannose receptor is a pattern recognition receptor involved in host defense.
AB  - The mannose receptor recognizes the patterns of carbohydrates that decorate the
      surfaces and cell walls of infectious agents. This macrophage and dendritic cell
      pattern-recognition receptor mediates endocytosis and phagocytosis. The mannose
      receptor is the prototype of a new family of multilectin receptor proteins
      (membrane-spanning receptors containing eight-ten lectin-like domains, which
      appear to play a key role in host defense) and provides a link between innate and
      adaptive immunity. Recent advances include the identification of three new
      members of the mannose receptor family, additional work on defining the molecular
      requirements for sugar binding, a role for the mannose receptor in antigen
      presentation of lipoglycan antigens and evidence that the mannose receptor is
      associated with a signal transduction pathway leading to cytokine production.

PMID- 9523109
TI  - Antimicrobial peptides of vertebrates.
AB  - The past year brought several discoveries that focused attention on antimicrobial
      peptides on epithelial surfaces. The malfunction of these substances was
      implicated as a cause of airway infections in cystic fibrosis. Other highlights
      included new insights into the relative selectivity of antimicrobial peptides for
      microbial membranes, their primary site of action.

PMID- 9523110
TI  - Role of the bactericidal/permeability-increasing protein in host defence.
AB  - Much has been learned recently about the structure and function of 55 kDa
      bactericidal/permeability-increasing protein (BPI), a member of a genomically
      conserved lipid-interactive protein family. Analysis of BPI fragments and the
      crystal structure of human BPI have established that BPI consists of two
      functionally distinct domains: a potently antibacterial and anti-endotoxin amino
      terminal domain (approximately 20 kDa) and a carboxy-terminal portion that
      imparts opsonic activity to BPI. A recombinant amino-terminal fragment (rBPI21)
      protects animals against the effects of Gram-negative bacteria and endotoxin. In
      man, rBPI21 is nontoxic and non-immunogenic and is in Phase II/III clinical
      trials with apparent therapeutic benefit.

PMID- 9523112
TI  - Antigen recognition.

PMID- 9523113
TI  - The pathogenetic role of HLA-B27 in chronic arthritis.
AB  - Population and peptide specificity analyses and studies in transgenic rodents
      support a role of HLA-B27 as an antigen-presenting molecule in
      spondyloarthropathy. The interplay between HLA-B27 and arthritogenic bacteria on
      infected cells suggests that HLA-B27 might also influence disease by other
      mechanisms. Recent genetic advances promise the identification of additional
      susceptibility genes.

PMID- 9523114
TI  - Unusual MHC-like molecules: CD1, Fc receptor, the hemochromatosis gene product,
      and viral homologs.
AB  - The MHC fold, with its well-characterized peptide-binding groove, can perform
      other functions in addition to presentation of antigenic peptides to T cells.
      Homologs of MHC molecules have diverse roles that include presentation of lipid
      antigens (by CD1), transport of immunoglobulins (by the neonatal Fc receptor),
      regulation of iron metabolism (by the hemochromatosis gene product, HFE), and
      deception of the host immune system (by viral homologs). Recent crystal
      structures of two of these non-standard MHC-like molecules have allowed
      comparison of the recognition properties of classical. MHC molecules with those
      of their unusual homologs.

PMID- 9523115
TI  - Conserved motifs in T-cell receptor CDR1 and CDR2: implications for ligand and
      CD8 co-receptor binding.
AB  - Recent X-ray crystallographic structures of the T-cell receptor (TCR) alpha and
      beta chains, as well as their trimolecular complexes with peptide-MHC ligand,
      have established their structural similarity with the immunoglobulin molecules.
      The complementarity-determining region (CDR1) and CDR2 encoded within the TCR
      germline variable (V) sequence genes are well conserved across different TCR V
      alpha and V beta subfamilies. Multiple sequence alignments have been made based
      on structural information; they indicate that there will be only a limited number
      of canonical conformations for the first and second CDR loops. The limited
      diversity shown by CDRs 1 and 2 contrasts with the extreme junctional CDR3
      diversity. Furthermore, CDR2 alignments have revealed conservation of a positive
      net charge in V alpha subfamilies. A model has been proposed for a direct
      interaction of the lateral part of CDR2 alpha with the negatively charged
      membrane-proximal 'stalk' region of the CD8 molecule.

PMID- 9523117
TI  - Role of B-cell and Fc receptors in the selection of T-cell epitopes.
AB  - The role of specific receptors in antigen internalization and presentation to
      helper T lymphocytes has been known for more than ten years. However, recent work
      indicates that internalization may not always be sufficient for antigen
      presentation. Indeed, antigen receptors such as B-cell receptors and Fc receptors
      may also be involved in the post-endocytic transport events that determine
      selectively the delivery of antigens to different endocytic compartments and
      thereby the presentation of different T-cell epitopes.

PMID- 9523116
TI  - CD4 and CD8: modulators of T-cell receptor recognition of antigen and of immune
      responses?
AB  - The response of T cells to antigen involves the participation of a number of
      distinct receptor-ligand engagements. The major players in the recognition of
      complexes of major histocompatibility complex molecules and peptide antigens are
      the T-cell receptors and the co-receptors CD4 and CD8. Progress in understanding
      the physical structures of these molecules, and how complexes between them are
      formed, is helping our understanding of how they participate in regulating the
      signals transduced to T cells.

PMID- 9523118
TI  - Endosomal proteolysis and MHC class II function.
AB  - Newly synthesized MHC class II alpha and beta chains associate with a protein
      chaperone, the invariant chain, which promotes the proper assembly of MHC class
      II complexes and their trafficking through cells and prevents their untimely
      loading with peptides. Efficient loading of MHC class II heterodimers with
      antigenic peptides requires concurrent proteolytic processing of both the
      invariant chain and endocytosed proteins. Recent studies have elucidated the
      critical roles of specific cysteine proteases, especially cathepsins S and L, in
      degrading the invariant chain and regulating the convergence of processed antigen
      and MHC class II dimers competent for peptide loading.

PMID- 9523119
TI  - Biochemical, cell biological and immunological issues surrounding the endoplasmic
      reticulum chaperone GRP94/gp96.
AB  - The past year has born witness to compelling demonstrations of the utility of
      peptide complexes with glucose regulated protein 94 (GRP94, also known as gp96)
      in cancer immunotherapy. Insights into the structural basis of peptide binding to
      GRP94 have been obtained and the role of the transporter for antigen presentation
      in defining the GRP94-bound peptide composition has been determined.

PMID- 9523120
TI  - Intracellular distribution of proteasomes.
AB  - Proteasomes are large multicatalytic proteinase complexes which are responsible
      for the selective degradation of cellular proteins and the production of peptides
      for antigen presentation. Proteasomes are localized both in the nucleus and in
      the cytoplasm, where some are associated with the endoplasmic reticulum membrane.
      Recent studies have shown differences in the localization of proteasome
      subpopulations, demonstrated the functional importance of endoplasmic reticulum
      associated proteasomes and investigated the role of putative nuclear localization
      signals and tyrosine phosphorylation on proteasome transport into the nucleus.

PMID- 9523121
TI  - Congenital diaphragmatic hernia from the womb to childhood.

PMID- 9523123
TI  - Observer variation in gynaecological cytopathology.

PMID- 9523122
TI  - Guidelines, standards and evidence in cervical screening: a personal view.

PMID- 9523124
TI  - Guidelines for anal cytology--to make cytological diagnosis and follow up much
      more reliable.
AB  - Anal intraepithelial neoplasia is a difficult diagnostic and management problem,
      particularly when it occurs in women with synchronous or metachronous genital
      intraepithelial neoplasia. Diagnosis and follow up by colposcopy is too
      specialized for widespread use, and although anal cytology has been used before
      it has been thought of as too inconsistent for practical application. This study
      standardized collection of specimens and investigated interobserver variation.
      The aim of the study was to determine whether observers could reliably
      distinguish high grade anal intraepithelial neoplasia from other conditions.
      Standardized collection of anal preparations was achieved in the host centre. A
      meeting of experienced cytopathologists was convened to agree guidelines for anal
      cytology. These guidelines were sent to the panel of six observers who were
      subsequently circulated with 30 cytopathological preparations in random order and
      asked to report them all. The results were collected and processed centrally.
      Four individuals were in complete agreement about those preparations which were
      inadequate for reporting, but two others had a lower threshold for rejecting
      preparations as inadequate. There was agreement between the observers in over 95%
      of cases in distinguishing high grade intraepithelial neoplasia from other
      cytological conditions. Kappa values range from 0.66 to 1.00. This study
      demonstrates that the provision of guidelines for the interpretation of anal
      cytopathological preparations can result in a high degree of interobserver
      agreement about the clinically important distinction between high grade anal
      intraepithelial neoplasia and other conditions. Anal cytology is a more useful
      technique for diagnosis and follow up of 'at risk' individuals than has
      previously been suggested, and should be utilized more widely in this group of
      patients.

PMID- 9523125
TI  - Cytological changes of the respiratory tract in young adults related to high
      levels of air pollution exposure.
AB  - Several histopathological and cytological studies have shown that lesions of the
      respiratory tract epithelium become increasingly severe with duration of exposure
      to high levels of urban air pollution as well as with ageing of studied
      population groups. In this study we investigated and compared findings of
      cytological abnormalities in sputa of young adults (21-25 years of age) exposed
      to high levels of air pollution since birth with those who were exposed in the
      last 2-3 years only. All subjects were non-smokers and were clinically healthy at
      the time of sampling. No significant differences in the incidence or severity of
      any of the cytological findings were found. The fact that even 10 times longer
      exposure to air pollution resulted in no major respiratory tract epithelial
      changes is, in our opinion, a result of the extremely efficient defence
      mechanisms and enormous regenerative potential of the respiratory tract of
      younger people.

PMID- 9523126
TI  - Detection of cytomegalovirus (CMV) in HIV+ patients: comparison of
      cytomorphology, immunocytochemistry and in situ hybridization.
AB  - CMV is regarded as an important pathogen in immunocompromised patients. This
      study compares three cytological methods of diagnosis of CMV in alcohol-fixed
      smears from bronchoalveolar lavage (BAL) specimens from 40 HIV+ patients, using
      cytomorphology (CM), immunocytochemical staining (ICC) and in situ hybridization
      (ISH). The results of CM are compared with virological detection methods using
      the detection of early fluorescent foci (DEAFF) 48-h culture technique and virus
      isolation studies (VISO 1). ICC was the most sensitive technique, identifying CMV
      in 13 cases, six of which were also positive on ISH. Cytomorphology was the least
      sensitive, with only one case showing diagnostic features of CMV cytopathic
      effect. One additional case showed morphological features suggesting viral
      infection but not specific for CMV. Both of these cases were confirmed by ICC and
      ISH. Virology studies identified CMV in all 13 cases and in an additional five
      cases. ICC detected two cases which were negative on the DEAFF test but which
      were later detectable by the VISO 1 technique. These findings support the
      usefulness of ISH and ICC in confirming CMV in cases where the infection was
      suspected on cytomorphological features. ISH and ICC also increase the detection
      of CMV in BAL smears not showing morphological features on CM.

PMID- 9523127
TI  - Peritoneal fluid cytology in serous borderline tumours of the ovary.
AB  - Peritoneal fluid cytology findings in three patients with serous borderline
      tumours of the ovary and peritoneal serous implants are presented. The specimens
      were characterized by papillary groups, acinar clusters and single neoplastic
      cells exhibiting cytoplasmic vacuolation and nuclear atypia of variable degree.
      The cytological appearances were initially considered consistent with ovarian
      adenocarcinoma in all cases. Histological correlation is required to avoid this
      diagnostic pitfall.

PMID- 9523128
TI  - Evaluation of 40 x 22 mm coverslip area in cervical cancer screening.
AB  - Nine hundred and twenty-three smears covered by 40 x 22 mm size coverslips were
      examined inside and outside the coverslip area to determine whether this
      coverslip size could be responsible for missed dyskaryotic cells in conventional
      cervical cancer screening. There was no instance when abnormal cells seen outside
      the coverslip were not also present within the coverslipped area.

PMID- 9523129
TI  - Parotid Castleman's disease.

PMID- 9523130
TI  - Disseminated alveolar rhabdomyosarcoma identified by cytology, presenting as
      bilateral pneumothoraces.

PMID- 9523131
TI  - Cystic lesions of the male breast harbouring malignancy--the role of wne needle
      aspiration (FNA)

PMID- 9523132
TI  - Certification, licensing, accreditation, and proficiency testing in
      cytopathology: let there be light!

PMID- 9523133
TI  - Fine-needle sampling of salivary gland lesions. VI. Cytological review of 44
      cases of primary salivary squamous-cell carcinoma with histological correlation.
AB  - Fine-needle sampling (FNS) of 44 salivary squamous cell carcinomas, including 34
      primary tumors arising from parotid gland, 6 local recurrences, and 4 lymph node
      cervical metastases, was performed in 44 patients. Cytologic diagnoses were
      concordant with histological diagnoses in 36 (81.8%) cases, whereas 5 (11.4%)
      cases were classified as malignant (carcinoma or adenocarcinoma), 1 (2.3%) case
      as suspicious, and 2 (4.5%) cases were false-negative (necrosis). No samples were
      unsatisfactory for cytologic evaluation.

PMID- 9523134
TI  - Diagnostic challenge of lobular carcinoma on aspiration cytology.
AB  - Lobular carcinomas are among the most difficult to type correctly on aspiration
      cytology. The inherent cytologic traits such as small size and bland appearance
      of cells in scanty aspirates may lead to false-negative diagnoses. Due to the low
      incidence of this form of breast carcinoma, there are few studies solely on
      lobular carcinoma, and the cytomorphologic features are not well defined. To
      delineate the cytomorphologic features and to assess their utility in correctly
      typing an aspirate as lobular carcinoma, we undertook a retrospective review of
      fine-needle aspirates from 31 cases of lobular carcinoma. The cytologic features
      of monomorphic cells, with scant cytoplasm, central vesicular nuclei, and
      inconspicuous nucleoli were found most helpful in correct typing of the cases.
      Intracytoplasmic vacuoles, nuclear grooves, and "Indian-file" arrangement of
      cells were corroborating features. We postulate that a combination of cytologic
      features makes the diagnostic delineation of lobular carcinomas possible on
      aspiration cytology.

PMID- 9523136
TI  - Demonstration of myxoid change in fine-needle aspiration of synovial sarcoma: a
      case report.
AB  - We report a case of synovial sarcoma with extensive myxoid change diagnosed by
      fine-needle aspiration. The patient is a 46-year-old woman who presented with a
      right paratibial mass. Aspiration cytology demonstrated a spindle cell neoplasm
      consistent with a synovial sarcoma but containing a prominent myxoid matrix. The
      clinical suspicion and cytologic diagnosis of a synovial sarcoma was confirmed by
      histologic and immunohistochemical findings. The cytologic differential diagnosis
      of spindle cell neoplasms with extensive myxoid change should be broadened to
      include synovial sarcoma.

PMID- 9523135
TI  - Synchronous malignancies detected by effusion cytology.
AB  - This case report describes the detection of two synchronous malignancies by
      cytologic examination of pleural effusion fluid in a 66-year-old man. The
      effusion cytology examination documented an adenocarcinoma in the background of
      chronic lymphocytic leukemia. The cytologic findings were confirmed by surgical
      biopsy and ancillary studies performed on the cytology specimen including
      immunocytochemistry, flow cytometry and electron microscopy. This case is unusual
      and to the best of our knowledge the first reported case in the English
      literature of two synchronous malignancies being diagnosed by effusion cytology.
      When two separate populations of atypical cells are present in the cytology
      smears, the possibility of multiple malignancies should be considered.

PMID- 9523137
TI  - Cytologic characteristics of parathyroid carcinoma: a case report.
AB  - A 44-yr-old man with a preoperative diagnosis of malignant mediastinal goiter
      underwent a preoperative fine-needle aspiration (FNA) biopsy. Fine-needle
      aspiration biopsy showed enlarged uniform nuclei, prominent nucleoli, few mitotic
      figures, karyolysis, anuclear cells, hyalinized nonepithelial cell clusters with
      hemosiderin deposits, and a perivascular pseudorosette pattern. This study
      reviewed the current literature dealing with this cytologic feature of
      parathyroid carcinoma. To our knowledge, this is the first report of an oxyphilic
      cell type of parathyroid carcinoma detected by FNA in the English-language
      literature.

PMID- 9523138
TI  - Odontogenic ghost cell tumor: a case report with cytologic findings.
AB  - Odontogenic ghost cell tumor is a rare, neoplastic form of calcifying odontogenic
      cyst (Gorlin cyst) whose cytologic features have not been previously reported. We
      present a case of odontogenic ghost cell tumor diagnosed by fine-needle
      aspiration biopsy (FNAB). The aspirate was characterized by (1) tissue fragments
      with basaloid epithelial cells, (2) "ghost" cells, (3) scattered multinucleated
      giant cells, (4) rare, eosinophilic, densely hyalinized "dentinoid" material in
      close association with the basaloid cells, and (5) calcific debris. The aspirate
      was diagnosed as "consistent with odontogenic ghost cell tumor." The cytologic
      features of odontogenic ghost cell tumor, as described, closely parallel the
      major histologic findings in this rare tumor. The differential diagnoses include
      other odontogenic tumors, squamous cell carcinoma, basaloid cell tumors of the
      salivary gland, and pilomatrixoma.

PMID- 9523139
TI  - Isolated pleural effusion with hematopoietic cells of mixed lineage in a patient
      receiving granulocyte-colony-stimulating factor after high-dose chemotherapy.
AB  - A 43-yr-old woman with recently diagnosed breast carcinoma presented with a right
      pleural effusion after a cycle of adjuvant, high-dose chemotherapy supported by
      peripheral blood progenitor cells (PBPC) and granulocyte-colony-stimulating
      factor (G-CSF, Filgrastim). Cytologic examination of the pleural aspirate yielded
      highly cellular material composed predominantly of cells of myeloid and
      macrophage/monocytic lineages. Despite clinical concern of a malignant effusion,
      the combination of cytologic and immunophenotypic examination yielded the correct
      diagnosis of a nonneoplastic effusion related to underlying pleural inflammation
      and possibly the administration of G-CSF.

PMID- 9523140
TI  - Hepatic angiosarcoma: aspiration biopsy cytology and immunocytochemical
      contribution.
AB  - In the absence of previously documented sarcoma, the initial diagnosis of
      angiosarcoma (AS) on fine-needle aspiration (FNA) biopsy of the liver is
      difficult. However, awareness of its occurrence and the assistance of
      immunocytochemical stains may aid in arriving at the correct diagnosis. In this
      paper, a 59-yr-old smoker and alcoholic woman presented after a syncopal episode
      and was found to have a palpable right abdominal mass. An abdominal CT scan
      confirmed multiple centrally necrotic liver masses, from which an FNA biopsy was
      obtained. The smears were bloody with groups of relatively dishesive and singly
      dispersed spindle cells in a somewhat necrotic background. The nuclei were
      elongated to ovoid-round with small nucleoli. The cytoplasm was ample and ill
      defined. The cells were reactive for factor VIII-related antigen and CD31 but
      negative for cytokeratin immunocytochemical stains, and a diagnosis of
      "suspicious for angiosarcoma" was entertained. The patient declined further
      studies or treatment but presented 4 mo later with light-headedness and
      hypoglycemia. Laparoscopic tissue biopsies of the liver/abdominal masses were
      obtained and revealed AS. Rarely, liver masses may represent AS. Pathologists
      should be aware of their cytomorphology and characteristic immunostaining to
      avoid their misinterpretation.

PMID- 9523141
TI  - Peritoneal washing in borderline epithelial ovarian tumors in women under 25: the
      use of cell block preparations.
AB  - Serous tumors of low malignant potential are uncommon in women under 30-years-old
      peritoneal washings play an important role in the diagnosis and prognosis of
      ovarian neoplasms. Accurate diagnosis of peritoneal washings is important in
      determining therapeutic regimens and in determining patient prognosis. In
      peritoneal washings, these tumors can be difficult to distinguish from reactive
      benign mesothelial cells. The cases of four women with borderline serous ovarian
      tumors, all of whom were under the age of 25, and had peritoneal washings which
      were positive for papillary tumors were reviewed.

PMID- 9523142
TI  - Diagnostic dilemmas in the interpretation of fine-needle aspirates of
      granulomatous prostatitis.
AB  - We have reassessed the fine-needle aspirates of ten cases previously diagnosed as
      granulomatous prostatitis (GP). Presence of unequivocal epithelioid granulomas
      (EG) or typical caseous necrosis was required for a smear to be diagnosed as
      nonspecific granulomatous prostatitis (NGP) or tuberculous prostatitis (TP),
      respectively. As a consequence only six cases met the criteria set up for the
      diagnosis of NGP and two for TP. The purpose of this revision was fourfold: to
      find out if there are other prostatic conditions which may be confused with GP
      cytologically, to investigate if there is a single cytologic finding that permits
      a confident diagnosis of GP, to find out if the etiology can be suggested on
      cytologic grounds alone, and, finally, to assess if carcinoma can be ruled out
      safely. We conclude the following: 1) There are various prostatic conditions
      which share some cytologic findings with GP; 2) the presence of distinct EG is
      the hallmark criterion of GP; 3) NGP and TP can be safely diagnosed cytologically
      but other forms of GP would require additional clinical data and ancillary
      techniques; and 4) carcinoma can be safely distinguished from GP cytologically.
      To succeed in this task the cytopathologist must diagnose carcinoma only if clear
      cut carcinoma cells are present and must be aware of the reactive changes induced
      by the inflammatory infiltrate both in duct/acinar and metaplastic cells.

PMID- 9523143
TI  - Transitional cell metaplasia of the cervix: a newly described entity in
      cervicovaginal smears.
AB  - Transitional cell metaplasia (TCM) of the cervix is rarely reported in the
      pathology literature. To our knowledge, no case reports describing TCM in
      cervicovaginal smears exist. We report the cytologic features of TCM and compare
      them with squamous-cell carcinoma in situ (CIS), tubal metaplasia (TM), and
      atrophy. One hundred twenty-seven cervicovaginal smears from 31 patients with
      histologically proven cervical TCM were reviewed: seven smears (five patients)
      showed TCM. Five smears each of CIS, TM, and atrophy were evaluated as to
      architecture, nuclear features, nuclear to cytoplasmic ratios, and cytoplasmic
      haloes for comparison to TCM. The features that characterize TCM and allow its
      distinction from CIS, TM, and atrophy include cohesive groups of streaming
      spindled nuclei with haloes, grooves, tapered ends, and wrinkled contours.

PMID- 9523144
TI  - Status of intraoperative cytology in the diagnosis of epithelioid hemangioma.
AB  - Whereas evaluation of the frozen section of a subcutaneous retro-auricular mass
      was equivocal, the correct diagnosis of epithelioid hemangioma could be suggested
      on examination of intraoperative cytological smears. It is proposed that in the
      absence of cytological cues of malignancy and in the presence of the proper
      clinical setting, the constellation of vascular structures, eosinophils,
      lymphocytes, and clusters of cuboidal cells with vacuoles in their abundant
      acidophilic cytoplasm is indicative of epithelioid hemangioma.

PMID- 9523145
TI  - Impact of training on cytotechnologists' interpretation of gynecologic thin-layer
      preparations.
AB  - This study determines the impact of training on the accurate interpretation of
      gynecologic thin-layer (TL) preparations. A workshop was developed, implemented
      and evaluated. Training materials were developed with the assistance of a Delphi
      panel. Sixty-six self-selected cytotechnologists participated. The experimental
      group consisted of 40 participants tested before and after an educational
      intervention, using gynecologic TL preparations. The 26 individuals in the
      comparison group were given the same pre- and post-tests as the experimental
      group, but the educational intervention was not offered until after the tests
      were administered. Data were analyzed using the t-test for independent and
      dependent samples, McNemar's test, point biserial correlation, and descriptive
      statistics. No significant difference in test scores was observed between the two
      groups. A correlation was observed between prior exposure to TL preparations and
      cytotechnologists' test scores. No correlation between experience and test scores
      was found.

PMID- 9523147
TI  - Pap piecework pay problematical still...

PMID- 9523146
TI  - Evaluation of the CytoRich technique for cervical smears.
AB  - The aim of the study was to assess the ability of the CytoRich System to prepare
      optimal gynaecological smears for diagnosis. The diagnostic results obtained from
      evaluating 1,325 matched slide-pairs, prepared using conventional methods and
      thin-layer technology, were compared. Cytological material for study was obtained
      using the combined spatula-cytobrush sampling technique. An assessment of the
      pitfalls associated with the interpretation of these smears was also undertaken.
      Diagnostic agreement was achieved in 1,272 of the 1,325 matched slide-pairs
      (96.0%), and these included 1,172 negative, 50 atypical, 24 low-grade squamous
      intraepithelial lesion (LSIL), 24 high-grade SIL (HSIL), and two malignancies. A
      total of 1,309 cases showed the same diagnosis within one diagnostic grade for an
      agreement of 98.8%. Evaluation of the 53 discordant diagnoses revealed that the
      conventional smear identified a significantly greater number of abnormal smears
      than the CytoRich technique (P < .001). It is suspected that the use of the
      combined spatula-cytobrush sampling technique did not provide adequate residual
      specimen for CytoRich after conventional smear preparation. This limitation is
      evidenced by the fact that the CytoRich preparations showed a lower yield of
      endocervical cells (P < .001) and infectious organisms (P < .001) than was
      demonstrated on conventional smears. Despite a number of diagnostic pitfalls
      associated with the interpretation of thin-layer smears, these preparations were
      easier and faster to screen and showed well-preserved and evenly distributed
      cells. Thin-layer smears were also characterised by a marked reduction in thick
      cell groups, air drying artifact, and obscuring inflammation and blood. The
      results confirm the limitation of the combined spatula-cytobrush technique in
      these types of comparative studies.

PMID- 9523148
TI  - Reply to Saitas et al.

PMID- 9523149
TI  - Identification of two further gap-junctional proteins, connexin40 and connexin45,
      in human myometrial smooth muscle cells at term.
AB  - The powerful synchronous contractions of the uterus in labor depend on electrical
      coupling of myometrial smooth muscle cells by gap junctions. In humans and other
      mammals, gap junctions are scarce in the myometrium of the non-pregnant uterus,
      but become abundant at term and/or with the onset of labor. Previous work has
      shown that the gap-junctional protein (connexin) expressed by human myometrial
      smooth muscle cells is connexin43, the same connexin type that predominates in
      cardiac muscle. Here we show that two further gap junctional proteins, connexin40
      and connexin45, are expressed by the myometrial smooth muscle cells of the human
      uterus at term. Transcripts encoding the human isoforms of these connexins were
      demonstrated by Northern blot analysis, and immunoconfocal microscopy enabled
      precise localization of the corresponding proteins to punctate contact points
      (i.e., gap junctions) between interacting smooth muscle cells. Double labeling
      demonstrated that, while some fluorescent spots comprise only connexin43, both
      connexin40 and connexin45 predominantly colocalize to connexin43-positive
      fluorescent spots. Triple labeling revealed that where all three connexin types
      were expressed, they frequently localized to the same gap junction spot. As gap
      junctional channels composed of different connexin types have been demonstrated
      in vitro to have different functional properties, multiple connexin expression
      may contribute to modulation of gap junction function in human myometrial smooth
      muscle cells in vivo.

PMID- 9523150
TI  - Centrosome structure and function is altered by chloral hydrate and diazepam
      during the first reproductive cell cycles in sea urchin eggs.
AB  - This paper explores the mode of action of the tranquillizers chloral hydrate and
      diazepam during fertilization and mitosis of the first reproductive cell cycles
      in sea urchin eggs. Most striking effects of these drugs are the alteration of
      centrosomal material and the abnormal microtubule configurations during exposure
      and after recovery from the drugs. This finding is utilized to study the
      mechanisms of centrosome compaction and decompaction and the dynamic
      configurational changes of centrosomal material and its interactions with
      microtubules. When 0.1% chloral hydrate or 350-750 microM diazepam is applied at
      specific phases during the first cell cycle of sea urchin eggs, expanded
      centrosomal material compacts at distinct regions and super-compacts into dense
      spheres while microtubules disassemble. When eggs are treated before pronuclear
      fusion, centrosomal material aggregates around each of the two pronuclei while
      microtubules disappear. Upon recovery, atypical asters oftentimes with multiple
      foci are formed from centrosomal material surrounding the pronuclei which
      indicates that the drugs have affected centrosomal material and prevent it from
      functioning normally. Electron microscopy and immunofluorescence studies with
      antibodies that routinely stain centrosomes in sea urchin eggs (4D2; and Ah-6)
      depict centrosomal material that is altered when compared to control cells. This
      centrosomal material is not able to reform normal microtubule patterns upon
      recovery but will form multiple asters around the two pronuclei. When cells are
      treated with 0.1% chloral hydrate or 350-750 microM diazepam during mitosis, the
      bipolar centrosomal material becomes compacted and aggregates into multiple dense
      spheres while spindle and polar microtubules disassemble. With increased
      incubation time, the smaller dense centrosome particles aggregate into bigger and
      fewer spheres. Upon recovery, unusual irregular microtubule configurations are
      formed from centrosomes that have lost their ability to reform normal mitotic
      figures. These results indicate that chloral hydrate and diazepam affect
      centrosome structure which results in the inability to reform normal microtubule
      formations and causes abnormal fertilization and mitosis.

PMID- 9523151
TI  - gamma-Tubulin is transiently associated with the Drosophila oocyte meiotic
      apparatus.
AB  - Evidence of a distinct microtubule organizing center in the meiotic apparatus of
      the fertilized Drosophila egg is provided by means of specific antibodies. This
      center contained gamma-tubulin and CP190 antigens and nucleated a transient array
      of radial microtubules. When the eggs were incubated with the microtubule
      depolymerizing drug colchicine, gamma-tubulin became undetectable in
      correspondence with the meiotic chromosomes, whereas it was visible near the
      sperm nucleus. Since the main difference between male and female microtubule
      organizing centers was the presence/absence of the centrioles, we propose that
      these organelles were mainly involved in the spatial organization of the
      microtubule nucleating material.

PMID- 9523152
TI  - Prion protein expression in muscle cells and toxicity of a prion protein
      fragment.
AB  - The prion protein (PrP) is a cell surface glycoprotein normally associated with
      neurones. Expression of the prion protein in cultured mouse myoblasts and
      myotubes suggests that the prion protein may play a physiological role in
      skeletal muscle. When myotubes differentiate from myoblasts prion protein
      expression is upregulated. Accompanying this increase is an upregulation of Cu/Zn
      superoxide dismutase (SOD-1) in myotubes. Muscle cells derived from mice
      deficient in cellular PrP (PrPc) show little increase in SOD-1 after
      differentiation from myoblasts to myotubes. Myoblasts and myotubes are resistant
      to the toxicity of a neurotoxic prion protein peptide (PrP106-126). However, in
      the presence of murine microglia, PrP106-126 causes a reduction in cell number.
      This effect is greater on myotubes than myoblasts. Even in the presence of
      microglia PrP106-126 is not toxic to muscle cells derived from PrP-deficient
      mice. Our results suggest that PrPc expression is associated with regulation of
      cellular resistance to oxidative stress in skeletal muscle.

PMID- 9523153
TI  - alpha B-crystallin and hsp25 in neonatal cardiac cells--differences in cellular
      localization under stress conditions.
AB  - Two members of the small heat shock protein family, alpha B-crystallin and hsp25,
      occur at high levels in the mammalian heart. To try and understand any
      differences in functioning, we compared their properties in cultured rat neonatal
      cardiac myocytes. Both proteins are stress-inducible, but the level of hsp25 is
      only slightly increased in cultured cardiac myocytes subjected to hyperthermic
      stress, while alpha B-crystallin levels even remain unchanged. Phosphorylation of
      alpha B-crystallin and to a lesser extent also of hsp25 is induced after the heat
      shock. Directly after heat stress, alpha B-crystallin and hsp25 are partly found
      in detergent-insoluble fractions, representing cytoskeletal/nuclear structures.
      Additionally, we show by confocal laser scanning microscopy that alpha B
      crystallin and hsp25 become associated with sarcomeric structures directly after
      the heat shock, indicating a cytoskeletal protective function. Four to six hours
      after the heat shock, both proteins reoccupy their original positions in the
      cytoplasm again. In contrast to alpha B-crystallin, hsp25 not only translocates
      to the cytoskeleton but also migrates to positions inside the nucleus. Despite
      the fact that both proteins are normally part of the same complex, their behavior
      in neonatal cardiac myocytes appears to be very different. The sarcomeric
      association of alpha B-crystallin occurs under milder conditions and persists for
      a longer period of time in comparison with hsp25. Our findings suggest that alpha
      B-crystallin and hsp25 are both involved in protection of the cytoskeleton during
      stress situations in the heart, although in different manners. In addition, hsp25
      also plays a role inside the nucleus.

PMID- 9523154
TI  - Parafusin is a membrane and vesicle associated protein that cycles at exocytosis.
AB  - In the unicellular eukaryote Paramecium tetraurelia, stimulation of exocytosis
      leads to Ca2+ activation of an alpha Glc-1-phosphodiesterase that
      dephosphoglucosylates the phosphoglycoprotein parafusin (PFUS). This process
      fails in exo mutant nd9 and also in the absence of Ca2+ influx upon stimulation
      suggesting that PFUS dephosphoglucosylation may be causally related to
      exocytosis. To further corroborate the hypothesis that PFUS is involved in the
      molecular events in exocytosis, we used laser confocal scanning microscopy and a
      PFUS specific peptide antibody to perform localization studies of PFUS in wild
      type (wt) and mutant Paramecium. In unstimulated wt cells, PFUS was associated
      both with the exocytic site of the cell membrane and with the membrane of the
      dense core secretory vesicles. Localization at these two sites was shown to be
      independent of each other since the exocytosis mutant (exo-) tam8, in which
      docking of its vesicles is blocked, still showed cell membrane staining.
      Immunofluorescence and immunoblotting of isolated intact secretory vesicles also
      revealed PFUS association. Upon stimulation of exocytosis, PFUS dissociated from
      both the dense core secretory vesicles and the cell membrane in a Ca(2+)
      dependent manner. During recovery of exocytic capacity, PFUS reassociated with
      the newly formed secretory vesicles in the cytoplasm prior to their docking at
      the exocytic sites. Immunoblot analysis of PFUS during this time showed no
      changes in levels of the protein. Stimulation of exocytosis in wt in Mg2+ buffer
      or in the exo- temperature sensitive mutant (nd9) at the non-permissive
      temperature did not lead to dissociation of the PFUS. We conclude that PFUS is a
      novel critical component whose cycling probably participates in the molecular
      exocytic fusion machinery in these cells.

PMID- 9523155
TI  - Intact Ras function is required for sustained activation and nuclear
      translocation of extracellular signal-regulated kinases in nerve growth factor
      stimulated PC12 cells.
AB  - PC12 pheochromocytoma cell lines expressing the dominant negative Ha-Ras Asn-17
      protein at different levels were used in this study to analyze the relationship
      between nerve growth factor (NGF)-induced activation of members of the mitogen
      activated protein kinase (MAPK) family, and neuritogenesis. In wild-type PC12
      cells, NGF rapidly stimulated the extracellular signal-regulated kinases (ERKs).
      Kinase activation was sustained and was followed by the translocation of ERK 1
      and ERK 2 into the nucleus ultimately leading to neurite outgrowth. In cells
      expressing relatively high levels of the inhibitory Ras protein, NGF stimulation
      of ERK 1 and ERK 2 as well as nuclear translocation of these protein kinases were
      greatly inhibited. In contrast, in PC12 subclones expressing low amounts of Ha
      Ras Asn-17 the peak of ERK activation was only slightly reduced, but became
      transient in nature and was not followed by nuclear translocation of ERKs 1 and
      2. Since all PC12 subclones expressing detectable levels of the dominant
      inhibitory Ras protein are resistant to NGF induction of neurite formation, our
      observations support the notion that sustained activation and translocation of
      ERKs into the nucleus are essential for NGF-induced neuronal differentiation of
      PC12 cells.

PMID- 9523156
TI  - Growth hormone stimulates multinucleated cell formation in long-term bone marrow
      cultures.
AB  - Although the effects of growth hormone on bone metabolism are well-documented,
      their role in the regulation of immune responses such as the inflammatory process
      has not been thoroughly explored. This study investigated the formation of
      multinucleated cells (MNC) in long-term human bone marrow cultures. Experiments
      using 1 and 100 ng/ml of human recombinant growth hormone (hGH) and 10(-7) M of
      1,25 dihydroxyvitamin D3 (VD3) showed that hGH increased the total number and
      nucleation of MNC. The effects of hGH were generally greater than those observed
      with VD3. Cytological and immunological characterization of MNC revealed several
      macrophage polykaryon features. MNC did not respond to calcitonin in a cyclic
      adenosine monophosphate assay and failed to resorb dentin slices. These results
      demonstrate that MNC formed in the presence of hGH and VD3 present an essentially
      macrophage polykaryon phenotype. In this context, growth hormone may be involved
      in the inflammatory process through upmodulation of macrophage polykaryon
      formation.

PMID- 9523158
TI  - Classification of human scleral spur cells in monolayer culture.
AB  - Aqueous humor outflow in primate eyes can be facilitated by ciliary muscle
      contraction, thereby widening fluid pathways through the trabecular meshwork.
      Recently in the scleral spur smooth muscle (sm) alpha-actin positive
      myofibroblast-like cells have been described which are in contact with the
      elastic fiber system of both the spur and trabecular meshwork. In the vicinity of
      these cells nerve terminals have been described. It is speculated that
      contraction of scleral spur cells can facilitate aqueous humor outflow, too. To
      provide a tool for further physiological and pharmacological studies monolayer
      cell cultures of human scleral spur have been established and characterized. For
      this purpose, cells derived from scleral spur, outer and inner trabecular
      meshwork and ciliary muscle tips from 7 donor eyes (43-87 years-old respectively,
      obtained 3-7 h post mortem) were grown in tissue culture medium and the different
      monolayer cells classified by their growth characteristics, and by
      immunohistochemical staining for vimentin, alpha-sm-actin, desmin, and alpha B
      crystallin, respectively. In addition, the presence of alpha B-crystallin mRNA
      and desmin mRNA was verified using the polymerase chain reaction (PCR)-method. We
      were able to characterize and distinguish human scleral spur cells from adjacent
      ciliary muscle and trabecular meshwork cells. Scleral spur cells (SPC) grew
      slower than ciliary muscle cells (CMC) but much faster than trabecular meshwork
      cells (TMC). All cells showed the same staining characteristics in vitro as they
      did in vivo. Scleral spur cells stained for vimentin and alpha-sm-actin, but not
      for desmin and alpha B-crystallin. The corresponding mRNAs of the latter two
      proteins could not be detected by PCR in the spur cells. Cells grew out from all
      donor eyes so that they actually provide a tool for further experimental studies.

PMID- 9523157
TI  - Loss of glucose transport in developing avian red cells.
AB  - Although red cells are generally associated with significant glucose transport
      and dependence on glycolysis, the mature red cells of some species (e.g. pig)
      show very low glucose transport. The generally low level of glucose transport in
      mature mammalian red cells is the result of maturational development, since it
      has been shown that even in red cells which have negligible glucose transport
      (e.g. pig red cells) the corresponding reticulocytes have significant glucose
      transport activity. The reticulocytes of the chicken, however, show minimal
      glucose transport activity. But this also is the result of maturational
      development, since chicken bone marrow red cells do transport glucose which
      diminishes upon cell maturation in vitro. The erythroblast chicken cell line,
      HD3, has high glucose transport activity which is lost upon induction to the red
      cell phenotype. Growing HD3 cells have much higher levels of transport than
      native chicken bone marrow cells and this is associated in part with elevation of
      glucose transporter (GLUT) mRNAs as a consequence of the expression of the v-erbA
      and v-erbB oncogenes. Both native bone marrow red cells and HD3 cells, when
      incubated in vitro under conditions where maturation occurs, show substantial
      losses of GLUT mRNA and GLUT proteins. To assess whether the inducers of
      maturation (hemin and butyrate) affect only the normally expressed GLUTs, chicken
      GLUT3 expressed from a different promoter was introduced into the HD3 cell by
      retroviral infection. Both the endogenous and exogenous transporters were lost
      upon cell differentiation and maturation, leaving a cell with low glucose
      transport activity. Conversely, in growing cells, butyrate had a pronounced
      effect on the elevation of the GLUT3 mRNA, especially on the exogenous GLUT3
      mRNA, and elevated glucose transport prior to differentiation. These results are
      consistent with the conclusion that chicken red cell development involves a
      requirement to reduce glucose transport activity. The near absence of glucose
      transport in the embryonic chicken red cell is thus due to a loss of this
      transporter during early development which occurs at an earlier developmental
      stage in the chicken red cell than in the mammalian red cell.

PMID- 9523159
TI  - Linkage disequilibria between Duffy blood groups, Fc gamma IIa and Fc gamma IIIb
      allotypes.
AB  - Fc gamma receptors (Fc gamma R) on white blood cells and the Duffy blood group
      antigens on red blood cells are coded for on the long arm of chromosome 1. They
      appear in different allotypic forms: the high responder/low responder (HR/LR)
      forms of Fc gamma RIIa, the alloantigens NA1 and NA2 of Fc gamma RIIIb and the
      Duffy blood group antigens Fya and Fyb. The aim of this study was to analyze
      possible linkage disequilibria between these allotypic immunomodulatory
      receptors, and thus provide evidence for the existence of a hypothetical gene
      complex. The Duffy phenotype was determined by the indirect antiglobulin test,
      NA1/NA2 phenotypes by the granulocyte agglutination test and the HR/LR
      polymorphism by an immunophagocytosis assay. Two haplotypes were found to be in
      linkage disequilibrium. For the haplotype NA2, Fyb we calculated a delta-value of
      -0.07 and for the haplotype NA1, HR we obtained a delta-value of -0.02.

PMID- 9523160
TI  - Common Caucasoid HLA-A1B8DR3 linkage group and immune responsiveness in a hybrid
      Venezuelan population: preliminary data.
AB  - A study performed on Venezuelans reveals a correlation between the common
      Caucasoid linkage group HLA-A1 B8 (A*0101, B*0801, DR3-) and increased
      lymphoproliferative activity stimulated by several concentrations of
      phytohemagglutin and concanavalin A in comparison to the group of persons
      possessing either the HLA-A1 (A*0101) antigen or the HLA-B8,DR3
      (B*0801,DRB1*03012) haplotype. The increased lymphoproliferative activity was
      simultaneously present with increased CD16 cell counts and decreased CD3 and
      total mononuclear counts. A further comparison of lymphocyte population and
      subpopulation counts in peripheral blood and serum Ig G,A,M levels in the HLA-A1+
      B8+ versus the HLA-A1-B8-high-responder individuals revealed increased CD16 cell
      counts and IgM levels in persons with the common Caucasoid haplotype (HLA-A1 B8).
      The data may suggest that some of the genes responsible for these levels or genes
      controlling their expression could be localized in or along the length of the
      common Caucasoid haplotype HLA-A1 B8 between the A and B loci of the MHC.

PMID- 9523161
TI  - Distribution of HLA-A, B and DR genes and haplotypes in the Irish population.
AB  - The distribution of HLA phenotypes, genes and haplotypes in the normal population
      is of considerable importance in, for example, disease susceptibility studies,
      platelet transfusion support and transplantation. HLA population genetics studies
      have been carried out on numerous population samples, however, no major studies
      have been performed on Irish Caucasoids. We have analysed the HLA-A, B and DR
      phenotypes of 1,910 healthy unrelated Irish blood donors recruited onto the Irish
      Bone Marrow Donor Panel. HLA typing was performed by a combination of serology,
      the polymerase chain reaction with sequence-specific primers and reverse
      hybridisation. We calculated Hardy-Weinberg fit, phenotype and gene frequencies
      and two- and three-locus haplotype frequencies, linkage disequilibrium (LD)
      values and their significance levels and relative LD values. Compared to many
      other European populations, the Irish show a high frequency of HLA-A1, B7, B8 and
      DR2 and a reduced frequency of HLA-A9, A30, B15 and DR4. Two- and three-locus
      haplotypes and the combinations of alleles in positive LD were all typical of
      northern European populations. However, the Irish have especially high
      frequencies of the common HLA-A1/B8, A2/B44, A3/B7, HLA-B8/DR3, B7/DR2, B44/DR4
      and B44/DR7 haplotypes, while the frequency of other relatively common
      haplotypes, e.g. HLA-A2/B15, is reduced. These frequencies are of particular
      value for estimating the likelihood of finding bone marrow donors in patients'
      extended families and unrelated donor panels.

PMID- 9523162
TI  - Evaluation of soluble CD44 splice variant v5 in the diagnosis and follow-up in
      breast cancer patients.
AB  - Aberrant expression of CD44 splice variants has been detected on a variety of
      human tumor cells. Overexpression of specific isoforms has been shown to be
      associated with metastasis and poor prognosis in breast cancer. We evaluated the
      possible utility of soluble CD44 splice variant v5 (sCD44v5) as a circulating,
      tumor-associated marker in breast cancer patients. Serum levels of sCD44v5 were
      determined in 147 healthy volunteers, in 53 patients with nonmalignant breast
      disease, in 85 patients with breast cancer at presentation, in 13 patients with
      recurrence and in 73 patients with active metastatic disease. Statistically, the
      levels at presentation in stages I-IV, in benign disease, and in a female control
      group were not significantly different. First longitudinal studies over 1-2 years
      in the follow-up of 28 patients who have remained tumor-free showed considerable
      between-patient variation while the intrapatient levels remained within
      relatively narrow limits. In patients with active metastatic disease, elevated
      levels of sCD44v5 (> 58 ng.ml-1) were detected in 50% of the cases with marked
      elevation in only 26%. In these cases, sCD44v5 correlated with the extent of
      metastatic disease and fell during clinical response to cytoreductive therapy. In
      comparison with CA15-3 in the patients' follow-up serum levels of sCD44v5 proved
      to be much less sensitive concerning lead time, percentage of raised serum levels
      at the time of recurrence and in metastatic disease. The value of sCD44v5
      determinations in breast cancer patients was further limited by the poor
      diagnostic specificity of this marker due to elevated levels in smokers and
      chronic inflammatory disease.

PMID- 9523163
TI  - Characterization, mapping and partial cDNA sequence of the 57-kD intracellular Ki
      1 antigen.
AB  - A novel antigen was identified by the cross-reactivity of the anti-CD30 antibody
      Ki-1. This 57-kD intracellular Ki-1 antigen (Ki-1/57) is induced upon activation
      of leukocytes and is transported to the nuclear compartment. We describe the
      partial cloning and sequencing of the Ki-1/57 cDNA from a lambda gt 11-cDNA
      library derived from the Hodgkin-analogous cell line L540. New monoclonal
      antibodies were produced against the recombinant Ki-1/57 protein fragment which
      were used to confirm that the Ki-1/57 antigen is associated with kinase activity
      and is expressed in a variety of tumor cell lines and in activated but not
      resting leukocytes. The Ki-1/57 gene was mapped to the bands 9q22.3-31 of human
      chromosome 9. This is an area which appears to be associated with secondary
      chromosomal aberrations in acute myeloid leukemias.

PMID- 9523164
TI  - Simple purification method of the antiphospholipid antibody from normal human
      plasma.
AB  - We have reported that rabbit serum contains a phospholipid (PL)/ganglioside
      binding protein which adsorbs to Sephacryl S-400 gel and agglutinates human red
      blood cells. A new protein similar to the PL/ganglioside-binding protein was
      simply purified from normal human plasma using Sephacryl S-400, Sepharose CL-4B
      and DEAE-Sepharose CL-6B columns. The purified protein was found to agglutinate
      rabbit red blood cells. The hemagglutination was specifically inhibited by two
      PL, phosphatidylserine and phosphatidylinositol, but not by any other PL,
      gangliosides, saccharides or glycoproteins tested. From analyses of the N
      terminal amino acid sequence and immunological specificity, the protein was
      identified to be a human immunoglobulin M.

PMID- 9523165
TI  - HLA-DQA1*0501 and DQB1*02 homozygosity and disease susceptibility in Spanish
      coeliac patients.
AB  - Coeliac disease (CD) susceptibility is strongly associated with HLA-DQA1*0501 and
      DQB1*02 alleles. There are discordant reports on whether homozygosity increases
      the risk. We genotyped HLA-DQA1*0501 and DQB1*02 in 50 CD patients, 100 parents,
      and 50 controls. Most patients (96%) were positive for DQA1*0501 (RR = 18.07, p <
      0.001), 94% for DQB1*02 (RR = 17.55, p < 0.001), and 92% for both alleles
      together (RR = 31.82, p < 0.001). DQA1*0501 was found in 52% of controls, DQB1*02
      in 44%, and only 24% had both alleles. Patients homozygosity or heterozygosity
      was estimated by assessing-in each case-whether one or both parents were carriers
      of the allele of risk. The frequencies of parents both positive for DQA1*0501
      (58%) and for DQB1*02 (53.1%) were higher than expected by the fact that the
      proband is a carrier. These findings suggest that the frequency of homozygosity
      is increased among CD patients, and therefore, homozygosity for either DQA1*0501
      or DQB1*02 represents a risk factor added to the fact of being a carrier.

PMID- 9523166
TI  - Evidence for TGF-beta-mediated 'defense' of the glomerulus: a blackguard molecule
      rehabilitated?
AB  - Transforming growth factor beta (TGF-beta) has been regarded as a 'blackguard
      molecule' that induces glomerular diseases. During the process of
      glomerulonephritis, upregulated TGF-beta stimulates the production of
      extracellular matrix and inhibits its degradation, leading to excessive matrix
      deposition. On the other hand, TGF-beta has the potential to be anti-inflammatory
      via inhibition of mitogenesis and production of inflammatory mediators by
      glomerular cells. This molecule strongly inactivates infiltrating cells,
      especially macrophages, which play a pivotal role in the generation of glomerular
      injury. The aim of this article is to summarize the potentially beneficial action
      of TGF-beta in the glomerulus and to address its 'bright side' in glomerular
      inflammation.

PMID- 9523167
TI  - What PAX genes do in the kidney.
AB  - Of the nine known PAX genes, only two (PAX2 and PAX8) are expressed in the
      developing kidney. Genetic evidence in mice and humans indicates that PAX2 plays
      a critical role in normal renal development and may sit atop a molecular cascade
      which unfolds during the transition from undifferentiated mesenchyme to the early
      stages of nephrogenesis. Less is known about the role of PAX8 in kidney
      development; although PAX8 is expressed in the S-shaped body and early proximal
      tubule, preliminary data suggest that renal morphogenesis is unaffected by its
      absence. In this review, we discuss the basic aspects of PAX gene structure and
      function and how mutations of PAX2 might interfere with structure of the
      developing nephron.

PMID- 9523168
TI  - How cytotoxic is nitric oxide?
AB  - Nitric oxide (NO) shows an unusual divergence of action, being utilised both as a
      physiological signalling molecule, and as a toxic mediator. NO-mediated cellular
      injury may arise by a variety of mechanisms, including disruption of
      mitochondrial respiration, enzyme inhibition, lipid peroxidation and genetic
      mutation. Toxicity is largely mediated via intermediates such as N2O3 and
      peroxynitrite, arising from the reaction of NO with either molecular oxygen or
      reactive oxygen species. In general, such reactions become significant only when
      high concentrations of NO are generated by the induction of nitric oxide
      synthase.

PMID- 9523169
TI  - Origin of glomerular capillaries: is the verdict in?
AB  - Classical studies with murine embryonic kidneys (metanephroi) grown in organ
      culture or on the avian chorio-allantoic membrane have suggested that kidney
      endothelia arise by ingrowth or angiogenesis. More recent studies, however,
      indicate that glomerular capillaries and arterioles may form in situ by
      vasculogenesis when more realistic experimental conditions are deployed: these
      include glomerulogenesis after transplantation of metanephroi to the nephrogenic
      renal cortex of mice as well as development in oculo. This conclusion is
      supported by the finding that receptor tyrosine kinases such as VEGFR-1/2 and Tie
      1, characteristic of endothelial precursors, are expressed in the metanephros at
      a stage when no patent vessels are apparent. Further studies are required to
      determine the origin of endothelial cells in renal vessels of larger calibre.

PMID- 9523170
TI  - Interleukin 10: a logical candidate for suppressing glomerular inflammation?
AB  - Inflammatory processes within the glomerulus are switched off by the local
      generation of anti-inflammatory mediators. These mediators include eicosanoids
      (e.g., lipoxins), anti-inflammatory cytokines (interleukins 4 and 13),
      antagonists of proinflammatory cytokines (interleukin 1 receptor antagonist),
      neuropoietic cytokines (leukemia inhibitory factor and interleukin 6), as well as
      deactivators of inflammatory macrophages (transforming growth factor beta and
      interleukin 10). They limit the effects of proinflammatory mediators by
      inhibiting their production, stability, or function. Recent attempts to reduce
      inflammatory lesions in experimental glomerulonephritis have focused on
      upregulating the expression of these anti-inflammatory mediators by using protein
      or gene transfer. In particular administration of interleukin 4, interleukin 1
      receptor antagonist, leukemia inhibitory factor, or interleukin 10 has been shown
      to be effective in the treatment of nephrotoxic nephritis. Of all the mediators
      already tested, interleukin 10 has the greatest potential because of its strong
      anti-inflammatory effects and weak adverse effects.

PMID- 9523171
TI  - Prevention of renal injury in diabetic MWF rats by angiotensin II antagonism.
AB  - We studied the effect of the combination of streptozotocin-induced diabetes and
      spontaneous renal injury in male MWF rats. Renal hemodynamics was studied by
      micropuncture 1 month after streptozotocin administration, and kidney
      morphological evaluation was performed after 4 months of diabetes. We also
      studied the effect of angiotensin II antagonism on development of renal lesions.
      Untreated animals developed mild hypertension, proteinuria, and
      glomerulosclerosis. Induction of diabetes, and maintenance of a moderate
      hyperglycemic state, was associated with slight but significant elevation in
      systemic and glomerular capillary blood pressure. Development of proteinuria was
      not accelerated or exacerbated by diabetes. Glomerular and tubular structural
      changes were also not worsened by diabetes. Antihypertensive treatment with an
      ACE inhibitor (benazepril) or with an AII receptor antagonist (valsartan) almost
      completely prevented systemic and glomerular capillary hypertension, proteinuria
      and renal structural changes. No significant differences in glomerular volume
      were observed among the four groups. That induction of experimental diabetes,
      although associated with glomerular capillary hypertension, did not aggravate the
      rate of progression of renal dysfunction would suggest that glomerular injury is
      not directly influenced by glomerular hemodynamic conditions in these animals.
      Prevention of renal functional and structural abnormalities by antagonism of AII
      activity in diabetic MWF rats suggests a pathogenetic role for angiotensin in
      inducing the renal disease in these animals.

PMID- 9523172
TI  - Beneficial effect of the long-term treatment with the combination of an ACE
      inhibitor and a calcium channel blocker on renal injury in rats with 5/6
      nephrectomy.
AB  - The effects of the addition of a calcium channel blocker, verapamil (20
      mg/kg/day) to an ACE inhibitor, trandolapril (0.7 mg/kg/day) in a 6-month
      treatment on renal insufficiency development in rats with 5/6th nephrectomy, were
      studied. Every month we measured heart rate and arterial pressure by the tail
      cuff method. Renal function studies were performed in metabolic cages. At the end
      of the study, renal tissue was prepared for light microscope analysis. Renal
      lesions were assessed by semiquantitative scores in a blind fashion. Corpuscular
      section area, intraglomerular and tubulointerstitial fibrosis were determined by
      digital image analysis with a specific software (Fibrosis HR) on syrium red
      stained renal sections. Trandolapril markedly increased the survival ratio that
      after 6 months reached 87% in comparison with 61% in untreated rats. No mortality
      was observed in rats treated with the combination of verapamil and trandolapril.
      Trandolapril treatment prevented the development of hypertension. The combination
      verapamil-trandolapril did not induce further reduction on blood pressure. The
      untreated group showed a marked proteinuria, that in the trandolapril group
      showed an important reduction. The verapamil + trandolapril group showed a
      proteinuria significantly smaller than that of all the other groups. Light
      microscopy semiquantitative studies of the renal injury showed that the
      trandolapril and verapamil + trandolapril groups had a marked reduction in
      glomerular and tubulointerstitial alterations, compared with untreated animals.
      Quantitative determinations of glomerular and interstitial fibrosis performed on
      syrium red-stained renal sections demonstrated that fibrosis was reduced when
      rats when treated with trandolapril and even more with verapamil + trandolapril
      when they were compared to untreated animals' values. In conclusion, long-term
      treatment with verapamil given in addition to trandolapril produces additional
      protection against progressive renal injury associated to subtotal nephrectomy.

PMID- 9523173
TI  - Oral supplementation of L-arginine prevents chronic cyclosporine nephrotoxicity
      in rats.
AB  - This study was performed to evaluate the effect of L-arginine (L-Arg) on the
      prevention of chronic cyclosporine (CsA) nephrotoxicity in rats. Rats pair-fed a
      low-salt diet (0.05%) were given CsA (15 mg/kg/day s.c.), CsA and L-Arg (L-Arg
      group, 1.25 g/l water), CsA and N-nitro-L-arginine methyl ester (L-NAME group, 70
      mg/l water) or vehicle. After 28 days, the L-Arg group had a higher glomerular
      filtration rate compared to the CsA (0.42 +/- 0.05 vs. 0.31 +/- 0.06 ml/min/100
      g, p < 0.05) and the L-NAME groups (vs. 0.19 +/- 0.04 ml/min/100 g, p < 0.05) and
      a significantly lower serum creatinine level compared to the CsA (0.70 +/- 0.06
      vs. 0.92 +/- 0.12 mg/dl, p < 0.05) and the L-NAME groups (vs. 1.21 +/- 0.17
      mg/dl, p < 0.05). The L-Arg group had less fibrosis, tubular injury (TI), and
      arteriolopathy than the CsA (fibrosis 0.39 +/- 0.14 vs. 0.74 +/- 0.15; TI 1.3 +/-
      0.3 vs. 2.0 +/- 0.1; arteriolopathy 33 +/- 7 vs. 48 +/- 17, p < 0.05,
      respectively) and the L-NAME groups (fibrosis vs. 1.67 +/- 0.32, TI vs. 2.6 +/-
      0.3, arteriolopathy vs. 63 +/- 10, p < 0.05, respectively). Plasma renin activity
      in the L-Arg group was less than in the CsA (18 +/- 2 vs. 23 +/- 3 ng Ang I/ml/h,
      p < 0.05) and the L-NAME groups (vs. 30 +/- 3 ng Ang I/ml/h, p < 0.05). Nitric
      oxide production in L-Arg group was higher than in the CsA (24.2 +/- 1.7 vs. 11.1
      +/- 1.5 mumol/24 h, p < 0.05) and the L-NAME groups (vs. 8.4 +/- 1.0 mumol/24 h,
      p < 0.05). In conclusion, the nitric oxide pathway is associated with the
      pathogenesis of chronic CsA nephrotoxicity, and exogenous L-Arg supplementation
      is effective in reducing chronic CsA nephrotoxicity in rats.

PMID- 9523175
TI  - Tubular epithelial cells as accessory cells for superantigen-induced T cell
      activation.
AB  - In various inflammatory kidney diseases, tubular epithelial cells (TEC) express
      major histocompatibility complex class II antigens. To assess whether they might
      have the capacity to directly activate T cells, human TEC in culture were treated
      with gamma interferon to induce class II expression. TEC were then cocultivated
      with staphylococcus enterotoxin and cloned T cells or highly purified peripheral
      T cells. After 1-2 days, release of interleukin 2 and of gamma interferon was
      seen; after 3-5 days T cell proliferation occurred. The proliferation could be
      inhibited by antibodies to class II antigens or by antibodies to ICAM-1; the
      latter is also expressed on TEC in inflammatory processes and on TEC in culture
      as well. In conclusion, human TEC might function as accessory cells for T cell
      activation and might support T cell dependent immune response.

PMID- 9523174
TI  - Mechanical stretch/relaxation stimulates a cellular renin-angiotensin system in
      cultured rat mesangial cells.
AB  - Angiotensin II (Ang II) may play a significant role mediating intraglomerular
      hypertension and glomerular sclerosis. Therefore, we investigated whether a model
      of pressure-induced stress, mechanical stretch/relaxation, affected the renin
      angiotensin system (RAS) in cultured rat mesangial cells. Type 1 Ang II receptor
      (AT1R) expression was assessed by 125I-Ang II binding and quantitative reverse
      transcription polymerase chain reaction. Stretch/relaxation increased steady
      state AT1R mRNA levels as well as specific [125I]Ang II binding. Increased AT1R
      expression was associated with altered AT1R signaling. Ang II (100 nM) increased
      total phosphoinositide hydrolysis in control cells (186 +/- 25%, n = 6; p < 0.025
      vs. no treatment). However, stretch/relaxation for 48 h further augmented AT1R
      mediated PI hydrolysis (293 +/- 38%, n = 6; p < 0.025 vs. Ang II treatment
      alone). We examined other RAS components in mesangial cells subjected to
      stretch/relaxation. Angiotensinogen, determined by radioimmunoassay of Ang I
      generation in conditioned media, increased with stretch/relaxation, and reverse
      transcription polymerase chain reaction demonstrated increased angiotensinogen
      gene expression in stretch/relaxation-treated cells. However, renin activity and
      angiotensin-converting-enzyme-like activity were unaffected by
      stretch/relaxation. Thus, mesangial cells maintain a local RAS similar to those
      described in other tissues, and AT1R expression and angiotensinogen production in
      this cellular RAS are increased by stretch/relaxation. It is likely that
      mesangial cells in vivo, exposed to variations in intraglomerular pressure, may
      regulate their responses via a local RAS.

PMID- 9523176
TI  - Low catalase activity in rats with ureteral ligation: relation to lipid
      peroxidation.
AB  - Progression of some renal diseases is characterized by generation of reactive
      oxygen metabolites that are also involved in the pathophysiology of obstructive
      nephropathy. Catalase activity and lipid peroxidation were investigated in rats
      with unilaterally (UUL) and bilaterally ligated ureters (BUL). Forty-eight hours
      after ligation, the animals were sacrificed, and enzyme activity as well as the
      malondialdehyde (MDA) concentration were measured in the plasma, kidneys and
      livers. The activity of catalase was significantly reduced in the plasma of the
      BUL rats and in the kidneys of both investigated groups. In the liver, catalase
      activity was decreased only in the BUL group. The MDA concentration in the plasma
      and kidneys of the BUL rats was significantly increased while in the liver it
      remained unchanged. These results suggest that lipid peroxidation in the induced
      uremic state could be responsible for catalase inactivation.

PMID- 9523177
TI  - Optimizing ribozymes for somatic cell gene therapy.
AB  - Therapeutic ribozymes are created through a multistep process that requires trial
      and error. There are few established rules governing ribozyme design, but
      guidelines are emerging. It is not yet known whether hammerheads and hairpins,
      the two ribozymes most widely studied as potential gene therapy agents, have the
      inherent capability to ablate single genes. Their capacity for specificity and
      selectivity remains to be explored through rigorous experimentation. These
      experiments require a battery of control molecules, the characteristics of which
      are outlined here. Methods for completing the steps in the ribozyme development
      process, from the selection of a target gene to the quantitation of RNA levels,
      are also presented and discussed.

PMID- 9523178
TI  - Antisense oligonucleotides.
AB  - Antisense technology was developed to inhibit gene expression by utilizing an
      oligonucleotide complementary to the mRNA which encodes the target gene. There
      are a few possible mechanisms for the inhibitory effects of antisense
      oligonucleotides. Among them, degradation of mRNA by RNase H is considered to be
      the major mechanism of action for antisense oligonucleotides. This technique was
      originally used to elucidate the function of a target gene, but may also have
      therapeutic applications, provided it is designed carefully and properly.

PMID- 9523179
TI  - Prospects of glutamate antagonists in the therapy of Parkinson's disease.
AB  - It has been suggested that the excitatory amino acid glutamate, acting as both a
      neurotoxin and a neurotransmitter, might play a central role in the
      pathophysiology of Parkinson's disease (PD). Intrinsic energetic defects of the
      neurons of the substantia nigra pars compacta, the brain area where the
      degenerative process of PD takes place, may render nigral neurons highly
      vulnerable to the effects of glutamate, which acts as a neurotoxin in the
      presence of impaired cellular energy metabolism. Degeneration of dopamine nigral
      neurons and striatal dopaminergic denervation cause a cascade of functional
      modifications in the activity of basal ganglia nuclei. Due to the close
      relationship that links dopaminergic and glutamatergic neurotransmission,
      glutamate is directly involved in the functional alterations of basal ganglia
      circuitry that lead to the development of parkinsonian motor symptoms. Drugs
      counteracting the effects of glutamate might therefore provide new protective and
      symptomatic strategies for therapy of PD.

PMID- 9523180
TI  - Experimental and clinical methods in the development of anti-Alzheimer drugs.
AB  - Methodology used for the development of anti-Alzheimer's disease (AD) drugs
      raises specific problems which are rarely examined in the literature. While the
      general development scheme is similar to that required for most drugs, some
      specific aspects must be analyzed, highly dominated by the dual goal of
      pharmacology, i.e., to obtain both symptomatic and etiopathogenic drugs. During
      preclinical studies, aged or lesioned animals are mainly useful for symptomatic
      drugs, whereas transgenic models or neurodegeneration-induced techniques would
      probably lead to etiopathogenic drugs potentially slowing down the process of AD.
      The first administrations of a new compound to human beings raise the question of
      the activity measurement techniques. Psychometry remains the most informative
      procedure to detect and analyze the activity of the drugs on the different
      components of cognition. Electrophysiology and neuroimaging need some
      complementary studies before they can be proposed as surrogate criteria in phase
      III trials. At this stage of development, American and the recently published
      European guidelines are of great help while insisting on long-term (6 months)
      placebo controlled trials with the use of the triple efficacy criterion: an
      objective cognition scale, a global assessment, and the opinion of the caregiver.
      In the long term, pharmacoepidemiology and pharmacoeconomy will have to confirm
      the rationale of this recent progress in the methodology of anti-AD drug
      development.

PMID- 9523181
TI  - Experimental study of antidiarrheal activity of Salicairine.
AB  - Experimental antidiarrheal activity of a traditionally used medication,
      Salicairine, was demonstrated in comparison to loperamide by significant
      inhibition of castor oil-induced diarrhea in mice (increases in hard faeces/total
      faeces ratio of 38 and 54 and 5 and 54% with respect to controls, at 0.5 and 1
      mL/kg and 1 and 2 mg/kg, respectively) and bisacodyl-induced increase in large
      intestine transit in rats (125 and 280 and 210% with respect to controls, at 0.4
      and 2 mL/kg Salicairine and 5 mg/kg loperamide, respectively). Salicairine was
      able to reduce contractions of isolated rat duodenum induced by barium chloride
      and acetylcholine, although not completely (that is about 60%) as seen with
      loperamide. Also, it did not change normal gastrointestinal transit in mice at
      doses of 0.5 to 1 mL/kg, conversely to loperamide which had a significant effect
      (decrease of 50%) at 2 mg/kg. Finally, Salicairine at 0.01 mL/mL, like loperamide
      at 0.2 mg/mL, significantly increased net fluid absorption in rat colon, either
      in basal conditions (30 and 64% respectively) or after a prostaglandin E1-induced
      increase in net fluid secretion (41 and 35%, respectively). The antidiarrheal
      activity of Salicairine is possibly related, at least in part, to an increase in
      colon net fluid absorption or a decrease in net fluid secretion.

PMID- 9523182
TI  - Enhancement of the vasodepressor response to adenosine by nicorandil in rats:
      comparison with cromakalim.
AB  - The effect of nicorandil on systemic blood pressure (SBP) and heart rate (HR)
      responses to adenosine was compared with that of cromakalim, an adenosine
      triphosphate (ATP)-sensitive K+ channel opener, in anesthetized rats. Intravenous
      (i.v.) adenosine in doses of 1-100 micrograms/kg elicited dose-dependent
      decreases in SBP, accompanied by decreases in HR. Potentiation of adenosine
      action by i.v. infusion of either nicorandil (10 or 30 micrograms/kg per min) or
      cromakalim (0.1 microgram/kg per min) occurred in all of the animals tested.
      After i.v. treatment with glibenclamide (20 mg/kg), an ATP-sensitive K+ channel
      blocker, not only adenosine action but also the enhancement of adenosine action
      by nicorandil and cromakalim were significantly attenuated. The present result
      indicates that the enhancement of the adenosine action by nicorandil and
      cromakalim appears to occur at least partly through ATP-sensitive K+ channel
      activation.

PMID- 9523183
TI  - Effect of activation of protein kinase A and of protein kinase C on the kinetics
      of the renal basolateral PAH transporter.
AB  - The aim of the present study was to examine the effect of activation of the
      protein kinase A (PKA) and protein kinase C (PKC) pathways on 3H-p-aminohippurate
      (PAH) uptake of isolated S2 segments of proximal tubules, microdissected from
      rabbit kidneys without the use of enzymatic agents. Because the tubules were not
      perfused, and hence were collapsed, the tubular uptake of 3H-PAH reflects
      transport across the basolateral membrane. The phorbol ester phorbol 12-myristate
      13-acetate (PMA) (10(-7) M), an activator of PKC, significantly increased tubular
      3H-PAH uptake with steady state conditions (by 115%), whereas dibutyryl cyclic
      adenosine monophosphate (db-cAMP) (10(-4) M) and forskolin (10(-4) M)
      significantly inhibited it (by 42% and 52%, respectively). Kinetic data, which
      were based on 15 sec PAH uptake measurements, revealed that PMA, after a 10 min
      incubation period, significantly enhanced Km and Vmax of the PAH transporter (Km
      from 174 +/- 22 to 447 +/- 91 microM, Vmax from 2.76 +/- 0.24 to 16.67 +/- 1.85
      pmol nL-1 min-1), whereas db-cAMP significantly decreased Vmax (from 2.76 +/-
      0.24 to 1.82 +/- 0.19 pmol nL-1 min-1). The Km value was also numerically lowered
      by dibutyryl-cAMP (from 174 +/- 22 to 139 +/- 21 microM), but this change did not
      reach statistical significance. The data provide evidence that short time
      activation of the PKC pathway 1) enhances the effectiveness of PAH transport into
      proximal S2 segments across the basolateral cell membrane, 2) increases the
      maximum transport rate of the PAH transporter and 3) decreases its affinity for
      PAH. Activation of the cAMP/PKA pathway induces the opposite effects.

PMID- 9523184
TI  - Regional differences in the vasorelaxant effects of nicorandil and amlodipine on
      isolated porcine coronary arteries.
AB  - The vasorelaxant effects of nicorandil, a K(+)-channel opener, and amlodipine, a
      dihydropyridine-type Ca(2+)-channel blocker, were investigated on partially and
      maximally K(+)-depolarized ring preparations from the porcine left anterior
      descending coronary artery. By comparing vascular responses in the proximal and
      distal parts of the epicardial segment, the scope of the study was to evaluate
      regional differences in the action of nicorandil and amlodipine. Nicorandil (10(
      7)-10(-4) M) shifted the K+ concentration-response curves to the right and
      depressed the maximal contractile responses in a concentration-dependent manner,
      consistent with K(+)-channel opening and secondary non-K(+)-channel opening
      mechanisms of action. Nicorandil had a significantly more potent relaxant effect
      in the proximal compared to the distal arterial rings contracted with 85 mM K+.
      Pretreatment with methylene blue (10(-5) M) did not significantly influence the
      regional difference in the action of nicorandil. Amlodipine (10(-9)-10(-6) M) had
      a significantly more potent and effective inhibitory and relaxant effect than
      nicorandil under the same conditions. In contrast to nicorandil, the effect of
      amlodipine was more prominent in the distal compared to the proximal vessel
      rings. The cumulative addition of extracellular Ca2+ exhibited a more potent
      contractile response in the distal rather than in the proximal rings. Nicorandil
      totally and amlodipine partly eliminated the contractile responses to the lowest
      concentration of Ca2+. The inhibitory effect of amlodipine on the contractile
      responses to higher Ca2+ concentrations was more pronounced than that of
      nicorandil. The results show that there are regional differences in the
      responsiveness of porcine coronary arteries to Ca2+, nicorandil and amlodipine.
      Our findings indicate that the regional difference in nicorandil-induced
      vasodilation was caused neither by the K(+)-channel opening nor by the nitrate
      like mechanism of action, but could be due to a direct Ca(2+)-influx blocking
      effect of the drug.

PMID- 9523185
TI  - Effects of carbamazepine on plasma extravasation and bronchoconstriction induced
      by substance P, capsaicin, acetaldehyde and histamine in guinea-pig lower
      airways.
AB  - We evaluated the in vivo effects of the pretreatment with carbamazepine (CBZ) at
      different doses (10, 20 and 40 mg/kg p.o.) on the Evans-blue extravasation and on
      bronchoconstriction induced by different substances in guinea-pig tracheal
      tissue. The drug dose-dependently inhibited the extravasation induced by
      substance P (SP), capsaicin and acetaldehyde, but not that induced by histamine.
      At the highest dose (40 mg/kg) CBZ inhibited the bronchoconstriction induced by
      SP, capsaicin and acetaldehyde, but not that produced by histamine
      administration. The in vitro study with guinea-pig tracheal preparation indicates
      that the drug does not interfere with the binding of SP to its receptors. Our
      results suggest that CBZ exerts a protective activity against the pro
      inflammatory action of SP.

PMID- 9523186
TI  - The in vitro pharmacological profile of KR31080, a nonpeptide AT1 receptor
      antagonist.
AB  - KR31080 (2-butyl-5-methyl-6-(1-oxopyridin-2-yl)-3-[[2'-(1H-tetrazol- 5-yl)
      biphenyl-4-yl]methyl]-3H-imidazo[4,5-b] pyridine) is a potent inhibitor of
      angiotensin type 1 (AT1) receptors in rabbit aorta and human recombinant AT1
      receptors. In the isolated rabbit thoracic aorta, KR31080 caused a nonparallel
      shift to the right of the concentration-response curves to angiotensin II (AII)
      with decreased maximal response (pD'2 = 10.1 +/- 0.1), but had no effect on the
      contractile response induced by norepinephrine. KR31080 inhibited specific
      [125I]AII binding to rabbit aortic membranes (AT1 receptors) and [125I][Sar1,
      Ile8]AII binding to human recombinant AT1 receptors in a concentration-dependent
      manner with IC50 values of 0.84 +/- 0.08 nM and 1.92 +/- 0.15 nM, respectively,
      but did not inhibit specific [125I]AII binding to bovine cerebellum membranes
      (AT2 receptors). In the Scatchard analysis, KR31080 interacted with rabbit aortic
      AT1 receptors in a competitive manner, similar to losartan. These results
      demonstrate that KR31080 is a potent and AT1 selective angiotensin receptor
      antagonist which exerts a competitive antagonism in the [125I]AII binding assay
      and insurmountable AT1 receptor antagonism in the functional study.

PMID- 9523187
TI  - Sparfloxacin but not levofloxacin or ofloxacin prolongs cardiac repolarization in
      rabbit Purkinje fibers.
AB  - Sparfloxacin, a fluoroquinolone antibacterial, has been reported to prolong
      cardiac repolarization in some patients. In this study, we have investigated the
      in vitro cardiac electrophysiological effects of two other fluoroquinolones,
      levofloxacin and ofloxacin, and compared them with those exerted by sparfloxacin.
      Cardiac action potentials have been recorded from rabbit Purkinje fibers using
      conventional glass microelectrodes. The influence of a sudden decrease in
      stimulation rate on repolarization is examined. It is found that ofloxacin and
      levofloxacin (1-100 microM) do not alter the action potential parameters even at
      a concentration as high as 100 microM. The stimulation rate is without effect on
      repolarization. On the contrary, sparfloxacin (1-100 microM) lengthens
      concentration-dependently the duration of action potential, this effect being
      significant from the concentration of 10 microM. A non significant decrease in
      maximal rate of rise of phase 0 depolarization was observed at the concentration
      of 100 microM. Under low stimulation rate, the sparfloxacin-induced prolonging
      effect was magnified and early afterdepolarizations occurred in one of seven
      fibers from the concentration of 30 microM and in four other fibers at the
      concentration of 100 microM. These results suggest that levofloxacin and
      ofloxacin had no effect on cardiac cellular electrophysiology whereas
      sparfloxacin exerts pure class III electrophysiological effects, which can
      explain the prolongation of QT interval observed clinically in some patients and
      might become arrhythmogenic in the presence of other predisposing factors.

PMID- 9523188
TI  - Positive chronotropic activity of bradykinin in the pithed normotensive rat.
AB  - The positive chronotropic effect of bradykinin was investigated in the pithed rat
      preparation. Cumulative treatment with bradykinin (0.20 nmol/kg-6.59 mumol/kg,
      intravenous [i.v.]) caused a dose-dependent increase in heart rate (HR) by a
      maximum of 80 +/- 3.3 beats min-1. In contrast, the active metabolite of
      bradykinin and selective bradykinin B1-receptor agonist, [des-Arg9]-bradykinin
      did not influence the spontaneous frequency of beating. Propranolol alone reduced
      the bradykinin-induced increase in HR and a combination of propranolol with
      prazosin abolished the chronotropic effect of bradykinin. The selective
      bradykinin B2 receptor antagonist. Hoe 140, dose-dependently shifted the dose
      response curves of bradykinin to the right, whereas the bradykinin B1 receptor
      antagonist, des-Arg10-[Leu9]-kallidin proved ineffective. From our experiments it
      may be concluded that bradykinin induces tachycardia in the pithed rat primarily
      by stimulating the sympathetic ganglia leading to the release of noradrenaline,
      which subsequently activates cardiac beta 1-adrenoceptors. The bradykinin-induced
      chronotropic effect is mediated by bradykinin B2-receptors, whereas B1-receptors
      appear not to be involved.

PMID- 9523189
TI  - Studies on the possible mechanism of the gastric mucosal protection by Calotropis
      procera--involvement of 5-lipoxygenase pathway.
AB  - The role of chloroform fraction of Calotropis procera root extract on different
      experimental ulcer models in rats was investigated. The extract demonstrated
      significant anti-ulcer activity against aspirin, indomethacin, ethanol,
      indomethacin + ethanol, or stress-induced ulcerations. Significant inhibition of
      gastric secretory volume and total acidity in pylorus ligated rats were observed
      to occur with the extract. It was also observed that the root extract
      significantly inhibited arachidonic acid metabolism induced by soyabean
      lipoxygenase. The results suggest that the anti-ulcer activity of the extract
      might be attributable to the inhibition of 5-lipoxygenase (5-LO).

PMID- 9523190
TI  - Effects of SR140333, a selective non-peptide NK1 receptor antagonist, on
      trigemino-thalamic nociceptive pathways in the rat.
AB  - Trigeminal stimulation of C-fibers increased c-fos expression within the
      trigeminal nucleus caudalis (NtV) and thalamic neuronal activity which both
      reflect the transmission of a nociceptive message. We examined the effects on
      both these phenomena of the selective NK1 and NK2 receptor antagonists, SR140333
      and SR48968. SR140333 (0.3, 1 and 3 micrograms/kg intravenously [i.v.]) dose
      dependently, reversibly and stereoselectively antagonized the increase of
      contralateral thalamic activity. This compound, when given i.v. (30
      micrograms/kg) or orally (10 mg/kg), also reduced the number of Fos-like
      immunoreactive cells particularly at the medial and caudal level of the NtV. In
      contrast, SR48968 did not exert any antagonistic effect either on thalamic
      activity or on Fos-like immunoreactivity. The data strongly suggest a
      preferential involvement of NK1 vs NK2 receptors in nociceptive transmission
      following trigeminal ganglion stimulation. Taken together, our results indicate
      that SR140333 could provide a potent drug for the relief of pain occurring under
      excessive activity of sensory trigeminal fibers.

PMID- 9523191
TI  - Nasal nitric oxide concentration is decreased in heart failure patients receiving
      nitrates.
AB  - Nitric oxide (NO) is a free radical gas and a short-lived messenger which has
      many paracrine functions. Direct assessment of NO production is very difficult in
      vivo. However, the paranasal cavities generate a high amount of NO which diffuses
      in the nasal cavity where it can be easily measured. Several studies have
      suggested alterations of the NO production in heart failure. Thus, we assessed
      nasal NO concentration in normal subjects and in heart failure patients. The
      nasal NO concentration averaged 227 +/- 10 ppb in the control group (n = 20), and
      210 +/- 10, 198 +/- 20 and 159 +/- 54 ppb in New York Heart Association (NYHA)
      class II (n = 30), III (n = 28) and IV (n = 7) patients, respectively (mean +/-
      standard error [SE], not significant using analysis of variance [ANOVA]). Nasal
      NO level was not influenced by age, sex or etiology of the heart failure or by
      treatment with frusemide, angiotensin-converting enzyme inhibitor or digoxin.
      However, treatment with NO-releasing drugs (nitrates or molsidomine)
      significantly decreased the nasal NO level in heart failure patients. A two-way
      ANOVA revealed that treatment with a NO-releasing drug influenced nasal NO
      concentration (P = 0.0005), whereas NYHA class did not (P = 0.23), with a trend
      towards an interaction between the two parameters (P = 0.09): the inhibitory
      effect of NO-releasing drug on nasal NO concentration was more pronounced in
      severe heart failure. In an additional group of 12 patients (NYHA class II or
      III), the nasal NO concentration was 174 +/- 19 ppb during NO-releasing drug
      treatment and increased to 231 +/- 27 ppb 3 days after withdrawal of the nitrates
      (P = 0.0007 using paired t-test). Conversely, the nasal NO concentration in
      another group of seven patients (NYHA class II or III) was 219 +/- 32 ppb without
      nitrate treatment and decreased to 188 +/- 28 ppb 7 days after nitrate addition
      (P = 0.02 using paired t-test). In contrast, the nasal NO concentration in
      another group of ten ischemic patients without heart failure was 203 +/- 25 ppb
      without nitrate treatment and was similar (207 +/- 28 ppb) 7 days after nitrate
      addition (not significant using paired t-test). In conclusion, nasal NO
      production is normal in heart failure, except in patients receiving NO-releasing
      drugs. Nasal NO concentration could be useful for investigating the mechanism(s)
      by which exogenous NO donors decrease endogenous NO production.

PMID- 9523192
TI  - Molecular cytogenetics of primary breast cancer by CGH.
AB  - Comparative genomic hybridization (CGH) reveals DNA sequence copy number changes
      that are shared among the different cell subpopulations present in a tumor and
      may help to delineate the average progression pathways of breast cancer. Previous
      CGH studies of breast cancer have concentrated on selected subgroups of breast
      cancer. Here, 55 unselected primary breast carcinomas were analyzed using
      optimized quality-controlled CGH procedures. Gains of 1q (67%) and 8q (49%) were
      the most frequent aberrations. Other recurrent gains were found at 33 chromosomal
      regions, with 16p, 5p12-14, 19q, 11q13-14, 17q12, 17q22-24, 19p, and 20q13 being
      most often (> 18%) involved. Losses found in > 18% of the tumors involved 8p,
      16q, 13q, 17p, 9p, Xq, 6q, 11q, and 18q. The total number of aberrations per
      tumor was highest in poorly differentiated (P = 0.01) and in DNA aneuploid (P =
      0.05) tumors. The high frequency of 1q gains and presence of +1q as the sole
      abnormality suggest that it is an early genetic event. In contrast, gains of 8q
      were most common in genetically and phenotypically advanced breast cancers. The
      vast majority of breast cancers (80%) have gains of 1q, 8q, or both, and 3
      changes (+1q, +8q, or -13q) account for 91% of the tumors. In conclusion, CGH
      results indicate that certain chromosomal imbalances are very often selected for,
      sometimes in a preferential order, during the progression of breast cancer.
      Further studies of such common changes may form the basis for a molecular
      cytogenetic classification of breast cancer.

PMID- 9523193
TI  - Allelic imbalance and cytogenetic deletion of 1p in colorectal adenomas: a target
      region identified between DIS199 and DIS234.
AB  - Both cytogenetic and molecular genetic analyses have shown that many colorectal
      adenomas carry an acquired deletion distally in the short arm of one chromosome
      1, but the two methods have never been brought to bear on the same tumors. The
      major part of this study was the analysis of 53 previously short-term cultured
      and karyotyped colorectal adenomas for allelic imbalance at eight microsatellite
      loci in 1p. Allelic imbalances were detected in seven of the 12 adenomas that had
      cytogenetically visible abnormalities of chromosome 1, as well as in four
      adenomas that either had a normal karyotype (one case) or had clonal chromosome
      abnormalities that did not seem to involve chromosome 1 (three cases); i.e., 30%
      of the adenomas had abnormalities involving 1p by the combined approach. A
      minimal region of overlap seemed to map to between DIS199 and DIS234, suggesting
      that this is a relevant target region. This genomic area contains the human
      homologue of the tumor modifier gene Mom1 (1p35-36.1), which, in mice, modifies
      the number of intestinal tumors in multiple intestinal neoplasia (Min)-mutated
      animals. To evaluate whether the imbalances corresponded to interstitial
      deletions of 1p material, we performed fluorescence in situ hybridization with a
      pericentromeric probe (15 adenomas) and a telomeric probe (6 adenomas) on
      uncultured cells from the 16 adenomas with chromosome 1 abnormalities. Except for
      three adenomas that had already been shown by banding analysis to have a trisomic
      pattern, two centromere 1 signals were invariably found. In the cases hybridized
      with the 1p-telomeric probe, we found the same frequencies of telomeric and
      centromeric signals, in agreement with the interpretation that the deletions were
      interstitial. One of the 53 adenomas had genomic instability, seen as new alleles
      at five of eight microsatellite loci. A comparison of the genetic findings with
      clinicopathologic data indicated that adenomas in the rectum have 1p
      abnormalities more often than do adenomas of the sigmoid colon, and that adenomas
      with 1p changes are larger than adenomas without abnormalities of chromosome 1.

PMID- 9523194
TI  - Genetic analysis of glioblastoma multiforme provides evidence for subgroups
      within the grade.
AB  - We analyzed 72 primary and 25 recurrent glioblastoma multiforme (GBM) samples for
      DNA sequence copy number abnormalities (CNAs) by comparative genomic
      hybridization (CGH). The number of aberrations per tumor ranged from 2 to 23 in
      primary GBM and 5 to 25 in recurrent GBM. There were 26 chromosome regions with
      CNAs in more than 20% of tumors. 7q22-36 was the most common gain and 10q25-26
      was the most common loss; each occurred in more than 70% of tumors. Of 27
      amplification sites, epidermal growth factor receptor (EGFR) was the most common;
      it was observed in 25% of primary GBMs. Statistical analysis based on pairwise
      correlation of CNAs indicated that there is more than one class of primary GBM.

PMID- 9523195
TI  - Screening for loss of heterozygosity and microsatellite instability in
      oligodendrogliomas.
AB  - To assess the frequency of loss of heterozygosity (LOH) and microsatellite
      instability (MI) in oligodendrogliomas, we performed an extensive screening of 16
      oligodendrogliomas and nine anaplastic oligodendrogliomas by using 132
      microsatellite markers on chromosomes 1 through 12 and 15 through 21. In total,
      3,135 loci were examined in 25 tumor samples. Only 33/1,965 (1.7%) of
      oligodendroglioma (low-grade) and 11/1,070 (1.0%) of anaplastic oligodendroglioma
      (high-grade) loci exhibited MI. High-frequency LOH regions were identified on
      chromosome arms 1p (31-73% for oligodendrogliomas and 60-100% for anaplastic
      oligodendrogliomas) and 19q (23-69% for oligodendrogliomas and 100% for
      anaplastic oligodendrogliomas). In addition, regions on chromosomes 4, 6, and 11
      were found to be lost in 30-80% of both oligodendrogliomas and anaplastic
      oligodendrogliomas. Increased LOH frequency of chromosome 17 (38-40%) was found
      only in high-grade oligodendrogliomas. The differences in LOH frequencies between
      low-grade and high-grade oligodendrogliomas in all loci combined and at three
      loci (DIS447, DIS226, and DIS252) on chromosome arm 1p were determined to be
      statistically significant [chi 2(1) = 20.2, P < 0.0001, and Fisher's exact test
      respective P values: 0.01, 0.03, and 0.02]. Our results provide evidence that
      microsatellite instability does not play an important role in the development of
      oligodendrogliomas. Furthermore, high LOH frequency on chromosomes 6 and 11 in
      addition to that identified previously on chromosomes 1, 19, and 4 suggests that
      multiple candidate tumor suppressor genes on these chromosomes may underlie the
      processes of initiation and/or progression in oligodendroglioma tumorigenesis.

PMID- 9523196
TI  - Multiple possible sites of BRCA2 interacting with DNA repair protein RAD51.
AB  - To investigate the biological consequences of aberrant BRCA2 protein during
      mammary carcinogenesis, we attempted to identify proteins that normally interact
      with BRCA2. By using a yeast two-hybrid system with a hybrid protein that
      contained residues 639-1,508 of BRCA2 protein fused to the GAL4 DNA-binding
      domain, we isolated five independent cDNA clones that encoded parts of RAD51
      protein, a human homolog of bacterial RecA. In vitro experiments using anti-RAD51
      antibody confirmed interaction of BRCA2 with RAD51. The RAD51-binding region of
      BRCA2 detected in the present study was distinct from the region reported
      recently. Further studies using smaller portions of BRCA2 defined at least two
      additional RAD51-binding domains, residues 982-1,066 and 1,139-1,266. Our results
      suggest that BRCA2 can interact with RAD51 through multiple sites of BRCA2 and
      that control of mitotic and meiotic recombination and/or of genomic integrity
      through binding to RAD51 may be a crucial mechanism by which BRCA2 suppresses
      abnormal proliferation of mammary cells.

PMID- 9523197
TI  - Identification of new partner chromosomes involved in fusions with the ETV6 (TEL)
      gene in hematologic malignancies.
AB  - Several partner genes on different chromosomes have been reported to be fused
      with the ETV6 gene (located in chromosome band 12p13), with different breakpoints
      and different frequencies, in various hematologic malignancies, particularly
      acute myeloid and lymphoid leukemias and myelodysplastic syndromes. By using FISH
      and molecular analyses, we have analyzed five different pediatric and adult
      patients carrying cytogenetic abnormalities involving 12p13. Our findings
      demonstrate that ETV6 was rearranged in all the cases analyzed. In particular,
      ETV6 was disrupted by translocations with chromosomal bands 7q22, 7q36, 9q11, and
      13q12, not previously described as partners of ETV6 in translocations, thus
      extending its promiscuity in rearranging with different partner genes.

PMID- 9523198
TI  - Isolation, mapping, and functional analysis of a novel human cDNA (BNIP3L)
      encoding a protein homologous to human NIP3.
AB  - We have isolated a novel cDNA that encodes a product showing significant sequence
      homology (56% identity) to human NIP3, a protein thought to interact with
      adenovirus E1B19kD and human BCL2 proteins. This cDNA contains an open reading
      frame of 657 nucleotides encoding a 219 amino acid polypeptide. The gene,
      designated BNIP3L, was expressed in all 16 normal human tissues examined; we
      mapped it to chromosome band 8p21 by fluorescence in situ hybridization.
      Introduction of the BNIP3L gene into six different cancer-cell lines caused
      significant growth suppression in each of them, while no such effect occurred
      when the antisense cDNA or the vector DNA was transfected, indicating that BNIP3L
      may function as a tumor suppressor.

PMID- 9523199
TI  - Homozygous deletion and frequent allelic loss of the 21q11.1-q21.1 region
      including the ANA gene in human lung carcinoma.
AB  - The frequent occurrence of 21q deletions in human non-small cell lung carcinoma
      (NSCLC) indicates the presence of a tumor suppressor gene on this chromosome arm.
      Since the ANA (Abundant in Neuroepithelium Area) gene, a member of an
      antiproliferative gene family, was mapped to 21q11.2-q21.1, we searched for
      genetic alterations of the ANA gene in human lung cancers. The gene was
      homozygously deleted in a human NSCLC cell line, Ma17. The gene was mapped in the
      0.33 Mb Not1 fragment at 21q21.1 of the Not1 restriction map for 21q. Loss of
      heterozygosity (LOH) at this locus was detected in 24/47 (51.1%) of NSCLC, and
      the frequency of LOH in brain metastases was significantly higher than that in
      stage I-II primary tumors (P = 0.018). These results suggested that the
      homozygously deleted region harbors a novel tumor suppressor gene involved in
      NSCLC progression. Since mutation of the ANA gene was not detected in other lung
      cancer cell lines and fresh lung tumors with LOH at this locus, it is unlikely
      that the ANA gene is a target gene inactivated by two mutational events in this
      chromosomal region. Physical mapping of the homozygously deleted region showed
      that the deletion had occurred interstitially at 21q11.1-q21.1 and the size of
      the deletion was estimated as being more than 3 Mb. Our mapping results will
      facilitate further efforts to identify a tumor suppressor gene on 21q.

PMID- 9523200
TI  - Identification of missense and truncating mutations in the BRCA1 gene in sporadic
      and familial breast and ovarian cancer.
AB  - The cloning of the breast and ovarian cancer susceptibility gene, BRCA1, allows
      direct estimation of the proportion of these cancers in the general population
      which can be attributed to germline mutations in this gene. We have used a
      combination of SSCP, heteroduplex analysis, and chemical cleavage of mismatch to
      screen the BRCA1 gene for mutations in the germline of 42 patients with breast or
      ovarian cancer who either have a moderate family history of these cancers, or
      have no family history of malignancy but a very early onset of the disease. A
      total of 30 sequence variants were observed, eight of which have not been
      described previously. Three sequence changes detected by chemical cleavage or
      heteroduplex analysis were missed by SSCP. The variants included 13 missense
      mutations, which were assessed for their pathogenic implications. Two of these
      (M18T and A1708E) are nonconservative substitutions which are located in
      evolutionarily conserved regions of the gene: M18T lies just upstream of the RING
      finger motif, and A1708E abolishes the transcriptional transactivation activity
      of the carboxy-terminal region of BRCA1. Mutations were observed in eight
      patients overall (19.0%), and protein-truncating mutations occurred in five of 27
      (18.5%) families with 1-3 cases of breast or ovarian cancer. The data suggest
      that a significant proportion of patients with a modest or no family history of
      these cancers may carry germline mutations in BRCA1.

PMID- 9523201
TI  - Follicular thyroid carcinoma: chromosome analysis of 19 cases.
AB  - Short-term cultures of 19 follicular thyroid carcinomas were examined
      cytogenetically. Clonal chromosomal changes were detected in 12 tumors. Two
      follicular carcinomas had only numerical alterations: one with a hyperdiploid
      karyotype with trisomies/polysomies of chromosomes 7 and 12, similar to the
      karyotypes previously identified in a sub-group of benign thyroid lesions, and
      the other with monosomy 20. In the remaining ten cases several structural
      chromosome anomalies were found. Loss of the short arm of chromosome 3 was
      observed in one tumor. In two widely invasive and metastasizing follicular
      carcinomas there was a t(7;8)(p15;q24) as the sole abnormality in one case and a
      der(8)t(7;8)(p15;q24) together with other cytogenetic alterations in the other
      case. This finding suggests that t(7;8)(p15;q24) may be related to an aggressive
      behavior of follicular thyroid carcinomas.

PMID- 9523202
TI  - The second ETV6 allele is not necessarily deleted in acute leukemias with a
      ETV6/ABL fusion.
AB  - The ETV6 (TEL) locus at chromosome band 12p 13 is a major site of translocations
      in acute leukemia, particularly in childhood acute lymphoblastic leukemia (ALL).
      In cases with translocations involving ETV6, the normal ETV6 allele is often
      deleted. In addition, loss of heterozygosity of ETV6 is frequently observed in
      childhood'ALL. Thus, it has been suggested that ETV6 may have an anti-oncogenic
      role to play, in addition to its oncogenic role. We have described an unusual
      case of ALL in which ETV6 is found fused to the ABL gene; ABL is normally
      activated by fusion to the BCR gene in the 9:22 translocation. We expanded the
      primary cells from this ETV6/ABL rearranged case of ALL in SCID animals and
      analyzed them for expression of both ETV6/ABL and the normal ETV6 mRNA. We found
      that both the rearranged and normal ETV6 mRNAs are expressed in the expanded cell
      population. Furthermore, sequence analysis of the ETV6 PCR product revealed no
      point mutations which would influence the amino acid sequence. Thus, deletion of
      the second ETV6 allele is not necessary for the transformation to leukemia by
      ETV6/ABL.

PMID- 9523203
TI  - Bilateral multiple renal oncocytomas and cysts associated with a constitutional
      translocation (8;9)(q24.1;q34.3) and a rare constitutional VHL missense
      substitution.
AB  - We report here on a patient with bilateral multifocal renal oncocytomas and
      cysts. Cytogenetic analysis of the patient's lymphocytes revealed a
      constitutional 46,XY,add (9)(q34.3) karyotype. The rearrangement was further
      resolved as a constitutional reciprocal t(8;9)(q24.1;q34.3) by microdissection
      and FISH. Because the 9q breakpoint was located in the same region as the
      tuberous sclerosis type I locus (TSC1), which is associated with renal tumors, we
      performed FISH with two TSC1 flanking cosmids that were mapped proximal to the 9q
      breakpoint, thus excluding its involvement. Loss of heterozygosity (LOH) studies
      of the tumors revealed LOH in chromosome I, further strengthening the molecular
      diagnosis of oncocytoma. A previously unreported germline missense substitution,
      Pro40Arg, in exon I of the VHL gene was also found in the patient's
      constitutional DNA, adding to the complexity of the genetic profile.

PMID- 9523204
TI  - Cytogenetic and molecular analysis of cellular atypical mesoblastic nephroma.
AB  - Cytogenetic and molecular analyses were performed on three cellular (atypical)
      congenital mesoblastic nephromas (CMNs). Two cases had trisomy 11; in one, it was
      the sole karyotypic abnormality, and the other had additional numerical changes
      as well as an isochromosome for the long arm of chromosome 1. Markers for the
      11p13 and 11p15 loci were present in three copies in these two CMNs. In the third
      CMN, two apparently normal copies of chromosome 11 were present together with
      additional numerical and structural chromosome changes. Because loss of
      heterozygosity was observed for both 11p13 and 11p15 markers, we assume that
      mitotic recombination occurred. Duplication and loss of imprinting of genes at
      11p15 has also been observed frequently in Wilms' tumor. We therefore propose
      that CMN and Wilms' tumor might share common genetic pathways.

PMID- 9523205
TI  - RAS mutations in pediatric leukemias with MLL gene rearrangements.
AB  - Translocations of the MLL gene at chromosome band 11q23 are the most common
      cytogenetic alterations in de novo leukemia in infants and in leukemia related to
      chemotherapy with DNA topoisomerase II inhibitors. Experiments on knock-in mice
      suggest that additional mutational events may by required for full
      leukemogenesis. Therefore, we used single-strand conformation polymorphism
      analysis and an allele-specific restriction enzyme assay to investigate the
      frequency of KRAS and NRAS mutations in 32 pediatric leukemias with translocation
      of the MLL gene. Of 25 de novo cases, 13 were acute lymphoblastic leukemia (ALL),
      10 were acute myeloid leukemia (AML), and 2 were biphenotypic. Three secondary
      leukemias were AML, 1 was biphenotypic, 1 was ALL, and 2 were diagnosed as
      myelodysplasia. The frequency of RAS mutations was 2 of 10 in de novo AML. Both
      mutations occurred in infant monoblastic variants. RAS mutations were otherwise
      absent in this series. This is the first report of congenital leukemias where
      translocation of the MLL gene and RAS mutation coexist. The frequency of RAS
      mutations in de novo AMLs with MLL gene translocations is similar to that in
      other forms of AML, but RAS mutations play a limited role in lymphoid and
      treatment-related leukemias with similar translocations.

PMID- 9523206
TI  - Mutations in the human homologue of the Drosophila patched gene in esophageal
      squamous cell carcinoma.
AB  - The human homologue (PTCH) of the Drosophila segment polarity gene patched has
      recently been identified as a tumor-suppressor gene for nevoid basal cell
      carcinoma syndrome and for sporadic basal cell carcinomas of the skin. We
      analyzed 30 esophageal squamous cell carcinomas (ESCC) for intrageneic mutations
      of the PTCH gene by polymerase chain reaction-single-strand conformation
      polymorphism analysis followed by DNA sequencing. We identified two somatic PTCH
      mutations (7%) in 30 ESCC. These were a nonsense mutation (CAG to TAG at codon
      361) in exon 8 and a missense mutation (CAG to CTG, Gln to Leu at codon 816) in
      exon 14. These tumors exhibited loss of heterozygosity at the polymorphic site of
      the PTCH gene. These results indicate that inactivation of the PTCH gene via a
      two-hit mechanism occurs in a subset of ESCC.

PMID- 9523207
TI  - CAT scans, PET scans, and genomic scans.
AB  - As we begin the long march toward genetic dissection of complex traits, it
      becomes necessary to develop optimum study designs and retool ourselves to face
      the emerging new challenges. Key issues pertaining to the design of genomic scans
      are reviewed, including: sampling unit, definition and refinement of phenotype,
      genotyping issues, one-stage vs. two-stage strategies, sample size and power, and
      cost and feasibility. It is emphasized that false positives should not be
      minimized in isolation from the issue of false negatives. Striking a practical
      balance between the two error rates is suggested. In terms of future directions
      to pursue, three areas are suggested: meta-analysis for pooling linkage results
      from multiple scans, rapid multivariate screening methods for increased power to
      detect quantitative trait loci (QTLs), and classification and regression trees
      (CART) methodology for handling heterogeneity and interactions. Finally, three
      recommendations are proposed for genomic scans. First, so as to minimize false
      negatives for a fixed sample size, it is recommended that we tolerate/accept a
      reasonable rate of false positives, on average, one false positive per individual
      scan. Second, so as to enable the use of relatively strict significance levels
      for interpreting the results from a genomic scan, it is highly recommended that
      the sample size be derived based on a significance level of at most 0.01 (and not
      0.05) and 90% power (and not 80%). Third, it is recommended that the stringent
      significance levels suggested by Lander and Kruglyak be used when pooling
      evidence from multiple genomic scans (and not at the level of individual scans).

PMID- 9523208
TI  - Syndrome X: is it for real?
AB  - The term syndrome X has been applied to the association of hypertension, non
      insulin-dependent diabetes mellitus (NIDDM), android obesity, insulin resistance,
      and dyslipidemia. In this paper, based on population samples from Tecumseh,
      Michigan, and Hiroshima, Japan, characterized by persons > or = 40 years of age,
      we examine the validity of regarding this constellation of traits as a true
      syndrome, i.e., an array of traits with a single, unifying pathophysiology
      underlying its components. Data were not available on insulin resistance and
      dyslipidemia, and obesity was expressed as body mass index (BMI) without the
      division into android and non-android types. The four ethnic-gender data sets
      were analyzed on the basis of two age classes, age > or = 40 years and age > or =
      50 years, and two obesity classes, BMI > or = 27 and > or = 30. A simple chi 2
      test of goodness-of-fit under a model of independence revealed non-random
      associations between hypertension, NIDDM, and BMI which were in part attributable
      to an excess of persons with all three traits. However, when the four data sets
      were subjected to separate log-linear analyses of the three-way association
      tables, none of the three-factor interaction terms (i.e., syndrome X) was
      significant. High significance was, however, observed in the two-factor
      interaction term for BMI*hypertension. It is concluded that the significant
      association between these three traits is driven by the BMI*hypertension
      interaction, and there is no evidence in these data sets of a significant role
      for a syndrome X. Genet.

PMID- 9523209
TI  - Univariate genetic analyses of epilepsy and seizures in a population-based twin
      study: the Virginia Twin Registry.
AB  - The purpose of this study was to examine the roles of genetic and environmental
      factors in the etiology of epilepsy and seizures in twins ascertained from the
      Virginia Twin Registry. Health history information on twins was collected by
      questionnaire. Concordance rates were calculated and used to estimate degree of
      concordance for seizure types in monozygotic (MZ) and dizygotic (DZ) twin pairs.
      Univariate twin analyses were performed for each epilepsy and seizure type to
      determine models which best explained observed variation. Health history
      information concerning epilepsy and febrile seizure occurrences was provided by
      members of 8,655 twin pairs; 6,684 of these supplied additional information
      reporting absence, complex partial, tonic-clonic, and unspecified seizures.
      Models including additive genetic and unique environmental factors best explained
      febrile seizures, epilepsy, complex partial seizures, and unspecified seizures.
      For complex partial seizures, however, the contributions of genetic and
      environmental effects did not vary across gender. These results show that, under
      univariate analysis methods, genetic factors played an important role in the
      expression of seizures in epilepsy, febrile seizures, unspecified seizures, and
      complex partial seizures. Additional support for these findings was provided by
      the concordance results for all categories except male twins reporting complex
      partial seizure occurrence. However, environmental influences still remained an
      important factor in seizure expression in these specific categories.

PMID- 9523211
TI  - Inheritance of the shared epitope and long-term outcomes of rheumatoid arthritis
      among community-based Caucasian females.
AB  - Multiple HLA-DRB1 alleles encoding a shared epitope (SE) at amino acid positions
      70-74 are associated with susceptibility and severity of rheumatoid arthritis
      (RA). We examined the relationship between the number and DRB1 genotype of SE
      alleles inherited and long-term outcomes of 180 community-based, Caucasian female
      RA patients followed annually for up to 12 years. Outcomes examined were
      physician assessment of RA course; annual measures of pain, function, and number
      of painful joint groups; history of joint surgery; and resource utilization.
      Models accounted for correlation among serial observations for the same patient
      and adjusted for patient age and disease stage. We examined two genetic models: a
      SE model in which patients were classified according to the number of SE copies
      inherited and a genotype model in which patients were categorized into one of six
      groups based on the inherited DRB1 genotype. We used likelihood ratio tests to
      compare these genetic models and to compare alternative model specifications. Our
      results demonstrate strong associations between inheritance of the SE and long
      term outcomes of community-based Caucasian females with RA. However, the pattern
      of results is not consistent across the outcomes. An additive model of risk is
      apparent for history of joint surgery and RA hospitalization. In contrast, a near
      reversal of this pattern is apparent for function, joint pain, pain rating, and
      RA physician visits. Finally, although the genotype model did not appear to be a
      better predictive model for RA outcomes overall, it did reveal some striking
      heterogeneity of SE alleles that was masked by the more parsimonious SE model.
      For example, the odds ratio (OR) for joint surgery for patients with 2 SE copies
      (OR = 3.16) reflects an average of 2 very different ORs when patients are further
      categorized according to genotype groups 4 and 5 (OR = 1.3 and 11.9,
      respectively).

PMID- 9523210
TI  - Increased risk for familial ovarian cancer among Jewish women: a population-based
      case-control study.
AB  - Jewish women have been reported to have a higher risk for familial breast cancer
      than non-Jewish women and to be more likely to carry mutations in breast cancer
      genes such as BRCA1. Because BRCA1 mutations also increase women's risk for
      ovarian cancer, we asked whether Jewish women are at higher risk for familial
      ovarian cancer than non-Jewish women. To determine the effects of 1) Jewish
      religion and 2) ovarian cancer in a first-degree relative on women's risk for
      epithelial ovarian cancer, we used data from a population-based, case-control
      study conducted in 8 geographic regions in the United States from 1980 through
      1982. The study group included 471 cases and 4,025 controls. Jewish women were
      more likely to have familial ovarian cancer than non-Jewish women [odds ratio
      (OR) = 8.4, 95% confidence interval (CI) = 2.6-28]. The risk of having ovarian
      cancer appeared to be greater in Jewish women having a first-degree relative with
      ovarian cancer (OR = 8.81, 95% CI = 2.02-38.23) than in non-Jewish women having a
      first-degree relative with ovarian cancer (OR = 3.01, 95% CI = 1.61-5.64), but
      differences between Jewish and non-Jewish women were not statistically
      significant. Jewish women with no first-degree relative with ovarian cancer had
      no increased risk for ovarian cancer (OR = 1.27, 95% CI = 0.74-2.91) compared to
      non-Jewish women. These results suggest that Jewish women may have a higher rate
      of familial ovarian cancer than non-Jewish women, but because the results are
      based on a small number of Jewish women with familial ovarian cancer, the results
      need to be confirmed in larger studies.

PMID- 9523212
TI  - Segregation analysis of two-locus models regulating apolipoprotein-A1 levels.
AB  - For quantitative traits associated with risk to complex diseases, such as heart
      disease, single major locus models are likely to be too simplistic. Currently,
      researchers have begun to use oligogenic models of inheritance, but the resolving
      power of these models remains to be determined. As the major apoprotein of high
      density lipoprotein (HDL), apolipoprotein A1 (apo-A1) is generally accepted as a
      protective factor for coronary artery disease. Although familial aggregation of
      apo-A1 levels has been reported, the mode of inheritance of apo-A1 remains ill
      defined. In the present study, we conducted a segregation analysis comparing a
      series of one-locus and two-locus univariate models for apo-A1 levels in a sample
      of 137 families ascertained through probands undergoing elective, diagnostic
      coronary angiography. A two-locus Mendelian model fit these data significantly
      better than any one-locus model. The incorporation of the second major locus into
      the model of inheritance leads to a significant improvement in the fit, and a
      significant decrease of the residual heritability. The best-fitting model
      included two loci with a reciprocal pattern of epistasis generating 4 distinct
      genotypic distributions. Taken together, these two major loci account for 58% of
      the variance of adjusted apo-A1 levels. This demonstration of a second major
      locus controlling apo-A1 levels may explain the equivocal results obtained from
      previous studies. This two-locus model may be more powerful for linkage analysis
      to map one or both of these quantitative trait loci.

PMID- 9523213
TI  - Method and computer program for controlling the family-wise alpha rate in gene
      association studies involving multiple phenotypes.
AB  - Multiple significance testing involving multiple phenotypes is not uncommon in
      the context of gene association studies but has remained largely unaddressed. If
      no adjustment is made for the multiple tests conducted, the type I error
      probability will exceed the nominal (per test) alpha level. Nevertheless, many
      investigators do not implement such adjustments. This may, in part, be because
      most available methods for adjusting the alpha rate either: 1) do not take the
      correlation structure among the variables into account and, therefore, tend to be
      overly stringent; or 2) do not allow statements to be made about specific
      variables but only about multivariate composites of variables. In this paper we
      develop a simulation-based method and computer program that holds the actual
      alpha rate to the nominal alpha rate but takes the correlation structure into
      account. We show that this method is more powerful than several common
      alternative approaches and that this power advantage increases as the number of
      variables and their intercorrelations increase. The method appears robust to
      marked non-normality and variance heterogeneity even with unequal numbers of
      subjects in each group. The fact that gene association studies with biallelic
      loci will have (at most) three groups (i.e., AA, Aa, aa) implies by the closure
      principle that, after detection of a significant result for a specific variable,
      pairwise comparisons for that variable can be conducted without further
      adjustment of the alpha level.

PMID- 9523215
TI  - Male lower urinary tract symptoms: is surgery always necessary?
AB  - A transurethral resection of the prostate is a good operation to relieve bladder
      outflow obstruction and has a low incidence of complications. However, recent
      work suggests that many men with symptoms may not require an operation, and it
      can probably be delayed in a majority for many years. This may be particularly
      important in old and frail patients. Many men with outflow obstruction have
      irritative symptoms such as urgency, frequency and nocturia; these could be
      treated with anticholinergics, provided they have normal flow rates and small or
      absent residual urine volumes. Pharmacological treatment to relieve outflow
      obstruction is disappointing. There may be some benefit from alpha-adrenoreceptor
      antagonists, but the place for 5 alpha-reductase inhibitors is still unsure. All
      drugs have side effects which are unacceptable in patients who are not bothered
      by their urinary symptoms and can wait for active treatment.

PMID- 9523214
TI  - FRAXA and FRAXE prevalence in patients with nonspecific mental retardation in the
      Hellenic population.
AB  - Mutations at FRAXA and FRAXE loci are due to expansions of a CGG trinucleotide
      repeat and are characterized by mental retardation. Here we report a pilot
      screening survey by means of cytogenetic and molecular methods of 433 unrelated
      retarded individuals and their parents of Hellenic origin coming from various
      parts of Greece and Cyprus. The purpose of the study was to estimate the
      frequency of FRAXA mutation in individuals with nonspecific mental retardation
      without family history and phenotypic stigmata in the Hellenic population. Five
      FRAXA-positive children (1.15%) were identified, of whom four were found to carry
      a full mutation and one a premutation. Furthermore we present preliminary data on
      a screening of FRAXE mutation frequency. We screened 257 male patients with
      nonspecific mental retardation, finding none positive for FRAXE mutation.

PMID- 9523216
TI  - Age differences in decision making: to take a risk or not?
AB  - A controlled laboratory experiment was used to assess the efficacy of the
      cognitive processes that underlie risk taking decision making in young and
      elderly people. Thirty-six participants took part in the study: half the subjects
      were elderly (mean age of 74) and the other half were young adults (mean age of
      19). The elderly participants made equivalent decisions to those of the control
      young adults. Both age-groups of participants systematically and comparably
      changed their behavior as a function of risk levels. Furthermore, the elderly
      participants, relative to young adults, did not exhibit any slowing down in the
      speed of processing the information involved in making risk taking decisions,
      reflecting that healthy elderly people are cognitively apt to making risk taking
      decisions. Both age-groups took comparably less time on the easy trials (trials
      with either low or high levels of risk) and comparably more time on the difficult
      trials (trials with medium levels of risk).

PMID- 9523217
TI  - Thiol-disulfide exchange systems in the liver of aging Fischer 344 rats.
AB  - The purpose of this study was to determine whether the major thiol-disulfide
      oxidoreductase activities of the rat liver were altered as a consequence of
      aging, and whether the alterations had any consequences in terms of hepatic thiol
      concentrations. Liver fractions were prepared from male and female Fischer 344
      rats at ages representing young adulthood (5 months), middle age (15 months) and
      old age (24-29 months), and the activities of the major thiol-disulfide exchange
      enzymes, together with protein and nonprotein sulfhydryl contents, were measured
      using spectrophotometric procedures. Thioltransferase, protein disulfide
      isomerase and thioredoxin reductase activities in livers of male and female rats
      were unchanged with aging, while glutathione disulfide (GSSG) reductase activity
      remained the same (in male livers) or increased (in female livers) as a
      consequence of aging. Both protein and nonprotein sulfhydryl concentrations were
      well maintained in old age. The absence of age-dependent alterations in the thiol
      protein disulfide exchange enzymes and the lack of compromise in the glutathione
      GSSG reductase system suggest that aged livers retain their capacity to regulate
      their thiol-disulfide redox balance under normal physiological conditions.

PMID- 9523218
TI  - Consequences of aging on mitochondrial respiratory chain enzymes in cultured
      human fibroblasts treated with ascorbate.
AB  - The activities of mitochondrial respiratory chain enzymes with and without
      ascorbate pretreatment were assayed in 10- to 20-week-old cultures of human
      fibroblasts. Aging was associated with a significant loss of respiratory chain
      enzyme activities. The presence of ascorbate in the medium reduced the rate of
      loss of these enzymes. Free radical-mediated injuries may also contribute to
      aging since the changes seen in respiratory chain enzyme activities are similar
      to those seen in oxidatively stressed cells. This study demonstrates an age
      related decline in mitochondrial respiratory chain activity as well as a
      protective role for ascorbate in aging.

PMID- 9523219
TI  - Comparison of normal and in vitro aging by non-enzymatic glycation as verified by
      differential scanning calorimetry.
AB  - The biomechanical parameters of rat tail tendons (RTTs) from 35-, 64-, 180- and
      900-day-old animals, corresponding to the early maturation phase, the mature and
      the senescent state were determined. The increase of maximum stiffness, ultimate
      stress and the elastic fraction of stress was most pronounced in the maturation
      phase. Differential scanning calorimetry (DSC) experiments were performed showing
      an almost linear increase of the collagen denaturation temperature in the age
      range 35-139 days. After 14 days incubation in glucose, we observed a marked
      increase of the biomechanical parameters in the young, an increase of maximum
      stiffness in mature, and only slight alterations of the biomechanical behavior in
      senescent RTTs. Both glucose incorporation and formation of advanced glycation
      end products were most prominent in 35-day-old RTTs. These biochemical findings
      were in excellent agreement with the enhancement of the collagen denaturation
      temperature after the incubation phase. Results suggest that the validity of the
      term 'accelerated aging' depends on the experimental approach, i.e. biomechanical
      tests, thermal isometric contraction or DSC.

PMID- 9523220
TI  - Splenic function in old age.
AB  - Hyposplenism has been reported in elderly people. However, from previous studies,
      it was not clear whether the observed alterations in splenic function were a
      physiologic effect of advanced age itself or a consequence of age-related
      diseases. As hyposplenism is believed to predispose to infections, autoimmune
      phenomena and thrombosis, this question is of great clinical concern. In the
      present study splenic function was assessed by counting the pitted red cells in
      65 healthy subjects aged 50-108 years. At variance from previous studies, our
      study population consisted of free-living individuals carefully selected in order
      to exclude any underlying disease. The percentage of pitted red cells in 37
      subjects over 70 years was significantly higher than in 28 younger subjects,
      although only 1 subject had a pitted red cell count indicating splenic
      hypofunction. A positive, but weak, correlation between the percentage of pitted
      red cells and age was also found when considering the whole population (rs =
      0.273, p = 0.029). In conclusion, although slightly reduced with advancing age,
      splenic function seems basically to be maintained in elderly people.

PMID- 9523221
TI  - Correlates of cognitive function in middle-aged adults. Atherosclerosis Risk in
      Communities (ARIC) Study Investigators.
AB  - The Atherosclerosis Risk in Communities Study administered cognitive function
      tests to more than 14,000 middle-aged adults in 1990-1992. The battery included
      the Delayed Word Recall test, the Digit Symbol Subtest of the Wechsler Adult
      Intelligence Scale-Revised, and the Controlled Oral Word Association (Word
      Fluency) test. Test performance was correlated positively with education level,
      negatively with age, was better in women than in men, and better in
      managers/professionals compared with other occupations. After controlling for
      these factors, race and community, the findings most consistent for both sexes
      were that Delayed Word Recall was negatively associated with depressive symptoms,
      diabetes, and fibrinogen level; the Digit Symbol Subtest was associated with
      marital status, negatively associated with depressive symptoms, smoking status,
      fibrinogen level, and carotid intima-media thickness, and positively associated
      with alcohol drinking and FEV1; and the Word Fluency test was positively
      associated with marital status, alcohol drinking, sports participation, and FEV1.
      Most of these cross-sectional results were in the predicted direction and have
      biologic plausibility, but mean differences between extreme categories were small
      (generally on the order of 0.1 to 0.2 of a standard deviation). Longitudinal
      study is warranted to evaluate whether small differences in middle-age lead to
      larger, clinically meaningful deficits with aging.

PMID- 9523222
TI  - Lipoprotein profile and high-density lipoproteins: subfractions distribution in
      centenarians.
AB  - In order to assess the role of HDL on longevity, we studied HDL subfraction
      distribution in centenarian women compared with a group of weight- and gender
      matched healthy normolipidemic controls. We did not find any significant
      difference in the mean plasma lipid, apolipoprotein, and Lp(a) levels. On the
      contrary, in spite of similar HDL-cholesterol concentrations (1.32 +/- 0.41
      mmol/l in centenarians vs. 1.32 +/- 0.25 mmol/l in controls, p = not
      significant), HDL2b and HDL3a levels were, respectively, significantly increased
      and significantly reduced in centenarians in comparison with controls (HDL2b 32.4
      +/- 9.2% in centenarians vs. 23.4 +/- 7.7% in controls, p < 0.002, and HDL3a 26.3
      +/- 9.8% in centenarians vs. 34.1 +/- 7.3% in controls, p < 0.01). Moreover,
      HDL2b levels were significantly raised and HDL3a levels were significantly
      reduced in centenarians in comparison with both 'middle-aged' and 'elderly'
      subjects, whereas no difference for any HDL subfraction was found between the two
      groups of controls of different ages. Age was significantly correlated with HDL2b
      and HDL3a (respectively, +0.452, p < 0.001, and -0.370, p < 0.01) in all
      subjects, but not with all the other lipid, lipoprotein and apolipoprotein
      parameters, but we observed a large overlapping of individual values of HDL2b
      between centenarians and controls. Since HDL2b levels were found to be inversely
      correlated with coronary heart disease risk, we could speculate that, in some
      cases, this may probably favor a healthy ageing, but long-term longitudinal
      studies are necessary to define the relative importance of HDL subfractions
      distribution as a marker of longevity. Probably other factors or clinical
      characteristics play a major role in the ageing process.

PMID- 9523223
TI  - Hemorheological changes during human aging.
AB  - Various researchers have reported an association of hemorheological,
      hematological and metabolic changes with human aging. In this article an attempt
      has been made to review the present understanding of hemorheological changes and
      their probable role in the development of certain disorders/diseases during
      aging. The rise in fibrinogen, blood viscosity, plasma viscosity, red cell
      rigidity, fibrin degradation products and early activation of the coagulation
      system are some of the most prominent findings. It is generally agreed that a
      rise in blood viscosity factors leads to a state of hypoperfusion which results
      in impaired microcirculation. The cumulative effect of these changes appears in
      the form of a disturbed blood flow profile in older subjects leading to the
      development or aggravation of various circulatory disorders. Many studies
      indicate that hemorheological parameters that change in a number of diseases
      prevalent during aging include hypertension, stroke, diabetes. In addition
      correlations found between hemorheological parameters in the aged and decrements
      in certain cognitive functions and behavioral patterns suggest that
      hemorheological changes contribute to nonclinical aging changes.

PMID- 9523224
TI  - Biology of chronic myelogenous leukemia.
AB  - This article reviews the biology of chronic myelogenous leukemia (CML) and its
      effect on the process of hematopoiesis. The relevance of the BCR-ABL fusion
      protein as well as murine models are also discussed. CML has been studied more
      extensively than any other malignancy, yet the correlation between the clinical
      symptoms of chronic phase CML and the BCR-ABL oncoprotein is poorly understood.
      Insights from recent efforts both to develop a good in vivo animal model and to
      characterize the effect of the BCR-ABL oncoprotein on relevant signal molecules
      may lead to a better understanding of the pathophysiology of chronic phase CML
      and, thereby, to the development of targeted therapeutic approaches.

PMID- 9523225
TI  - Clinical course and therapy of chronic myelogenous leukemia with interferon-alpha
      and chemotherapy.
AB  - This article begins with a review of the natural history of chronic myelogenous
      leukemia (CML), with an emphasis on prognostic features. Current standard therapy
      of CML with interferon-alpha based regimens, and interferon-alpha, in the context
      of allogenic stem cell transplantation is then discussed. Finally, some
      potentially effective novel agents including homoharringtonine, decitabine, ATRA,
      and topotecan are described.

PMID- 9523226
TI  - Related donor bone marrow transplantation for chronic myelogenous leukemia.
AB  - HLA-identical sibling bone marrow transplantation is an effective and commonly
      used therapy for young patients with chronic myelogenous leukemia. Efficacy
      results from high dose chemotherapy, with or without radiation, given for
      pretransplant conditioning and from immune-mediated antileukemia effects of the
      graft. The primary determinant of outcome is the patient's disease phase at time
      of transplant, with best results observed when transplants are done early in the
      chronic phase. Major causes of treatment failure are graft-versus-host disease
      and other transplant-related complications. Relatively few patients relapse
      unless the disease is advanced pretransplant or the donor bone marrow is T-cell
      depleted.

PMID- 9523227
TI  - Unrelated donor transplant therapy for chronic myelogenous leukemia.
AB  - Unrelated donor transplant therapy for chronic myelogenous leukemia is both
      feasible and effective. As discussed in this article, clinical outcome can be
      predicted based on several patient characteristics and transplant conditions.
      Highly selected subsets of patients experience outcomes not appreciably different
      from recipients of related donor transplants. In many cases, however, unrelated
      donor transplant is associated with significant peritransplant mortality and
      other complications. The impact of recent improvements in donor-recipient typing,
      marrow procurement, graft-versus-host disease prevention and treatment, medical
      support, and donor selection should soon become apparent.

PMID- 9523228
TI  - Effect of HLA matching on outcome of related and unrelated donor transplantation
      therapy for chronic myelogenous leukemia.
AB  - This article examines the diversity and biologic role of human lymphocyte antigen
      (HLA) genes as related to marrow transplantation for chronic myelogenous leukemia
      (CML). A better understanding of the nature and function of HLA variation is
      necessary as unrelated marrow transplantation evolves into a safe and effective
      treatment for CML. HLA matching is an important aspect of donor selection
      criteria and has a role in engraftment as well as the development of graft-versus
      host disease and tolerance after transplant.

PMID- 9523229
TI  - Infusion of donor peripheral blood mononuclear cells to treat relapse after
      transplantation for chronic myelogenous leukemia.
AB  - Until recently, the only curative therapy for patients with chronic myelogenous
      leukemia (CML) who relapse after allogeneic bone marrow transplantation (BMT) has
      been second allogeneic BMT. Recently, donor mononuclear cells have been given to
      patients with relapsed CML to induce a potent graft-versus-leukemia reaction and
      re-establish complete remissions in the majority of patients without the need for
      a second transplant. The extraordinary success of donor mononuclear cell
      infusions shows that it is possible to manipulate and harness the graft-versus
      leukemia (GVL) reaction for clinical benefit. The identity of the effector cells
      and target antigens is unclear, but intensive investigation is beginning to
      define the complex cytokine and cellular interactions that mediate GVL
      reactivity. Current clinical trials are investigating strategies that will retain
      and enhance the GVL effects while limiting toxicity from this therapy.
      Ultimately, the ability to harness the GVL potential of allogeneic donor cells
      without excessive toxicity from graft-versus-host disease will be a central
      challenge in BMT and cellular immunotherapy.

PMID- 9523230
TI  - Autologous transplantation for the treatment of chronic myelogenous leukemia.
AB  - There is evidence that benign, Ph-negative hematopoietic progenitors persist in
      the marrow and blood of some patients with chronic myelogenous leukemia (CML). A
      number of pilot studies using purged and unpurged marrow or peripheral blood
      autografts have demonstrated that autologous transplantation can result in
      transient cytogenetic responses in CML. Although not curative, this procedure may
      be associated with longer-than-expected patient survival and represents an
      alternative treatment for patients ineligible for allogeneic transplantation and
      not responding to interferon-alpha therapy. Several novel approaches are being
      developed to improve graft purging and eliminate residual leukemia post
      transplantation. Such approaches may allow for long-term restoration of Ph
      negative hematopoiesis following the procedure.

PMID- 9523231
TI  - Innovative therapy for chronic myelogenous leukemia.
AB  - Innovative therapies for chronic myelogenous leukemia (CML) have focused mainly
      on combining autologous transplantation with another modality of therapy for
      purging of the graft or treatment of the patient after transplant. Of the three
      categories of innovative therapies, two are based on studies that demonstrate the
      bcr/abl gene rearrangement in the pathogenesis of CML, whereas the third is based
      on the observation that allogeneic disparity is important to maintain remissions
      in CML. The rationale and data supporting these innovative approaches are
      reviewed in this article and future strategies are discussed.

PMID- 9523232
TI  - Production of a single chain anti-CEA antibody from the hybridoma cell line
      T84.66 using a modified colony-lift selection procedure to detect antigen
      positive ScFv bacterial clones.
AB  - Recombinant single chain Fv (scFv) antibodies offer many advantages over mouse
      monoclonal antibodies (MAbs) such as faster clearance from blood, improved tumor
      localization, reduced human anti-mouse antibody (HAMA) response, and the
      availability to manipulate the scFv through genetic approaches. The scFv antibody
      (designated RK10.2) was generated using anti-CEA T84.66 hybridoma cells as a
      source of genetic starting material and the Pharmacia Recombinant Phage Antibody
      System (RPAS). Escherichia coli clones expressing antigen-positive soluble scFv
      were identified using a modified colony-life selection procedure and antigen
      coated filters. The resultant anti-CEA scFv (designated RK10.2) had a molecular
      weight of approximately 33.6 kDa and an isoelectric point of 5.2 at 15 degrees C.
      The RK10.2 scFv interacted with LS174 T cells bearing the CEA antigen and
      inhibited the anti-CEA MAb/CEA antigen interaction in ELISA and the anti-CEA
      MAb/LS174 T cell interaction in a RIA. The modified colony-lift approach
      circumvented the more time-consuming phage-display approach that is normally
      taken to affinity select for antigen-positive scFv clones.

PMID- 9523233
TI  - Monoclonal antibodies define a cellular antigen involved in HTLV-I infection.
AB  - The exact mechanism by which the human T cell leukemia viruses (HTLV) infects
      target cells remains unclear; although some molecules have been identified to be
      important in viral infection and entry. To investigate these phenomena, we
      generated a panel of monoclonal antibodies (MAb) against a B cell line (BJAB-WH)
      which is highly permissive for infection with HTLV. These MAb have been used to
      further characterize the membrane molecules important for HTLV infection. Three
      of these MAb designated 4.2.3, 3.3.10, and 11.2.3 were capable of inhibiting
      syncytium formation induced in human B and T cell lines (i.e., BJAB-WH and SupT
      1, respectively) by co-culture with HTLV-I infected MT-2 cells. All of these MAbs
      immunoprecipitated a 80-85 kDa antigen from the lysates of metabolically labeled
      BJAB-WH but not from BJAB-CC/84, a noninfectible target cell. The binding of
      these MAb with different HTLV target cells was analyzed and compared with binding
      of polyclonal monospecific antisera to the same cell lines. A 80-85 kDa membrane
      glycoprotein was isolated with an immunoaffinity chromatographic column
      constructed with MAbs 4.2.3 and 3.3.10. This cellular antigen was capable of
      inhibiting HTLV I/MT-2 induced fusion. This is the first direct demonstration
      that a 80-85 kDa cellular glycoprotein is directly involved in HTLV I/II
      infection and syncytium formation.

PMID- 9523234
TI  - Establishment of epitope-defined monoclonal antibodies with specificity for
      fibroblast growth factor receptor types 1 and 2.
AB  - The development of specific antibody probes for characterizing the expression of
      the family of 4 fibroblast growth factor receptor (FGFR) types has been difficult
      because of their close homology to each other and high degree of evolutionary
      conservation. Of the existing anti-FGFR monoclonal antibodies (MAbs), there are
      few that are useful for staining paraffin-embedded tissues. We have raised MAbs
      against human FGFR1 and FGFR2 in both rats and mice using bacterial recombinant
      receptor fusion proteins as immunogens. We used peptide epitope mapping to
      characterize the immune sera and the selected MAbs. Immunized animals were
      selected that displayed the broadest reactivity against epitopes unique to the
      immunizing receptor type. We produced FGFR1 specific MAbs that bind epitopes in
      immunoglobulin domain I (Ig-I) and FGFR2 specific MAbs that bind epitopes in Ig
      I, Ig-II, and the acid box. The specificity of the antibodies was demonstrated by
      ELISA and immunoblot analysis of purified recombinant FGFR1 and FGFR2
      extracellular domains produced both in E. coli and in eucaryotic cells. Based on
      the lack of epitope homology, these MAbs would not be expected to cross-react
      with FGFR3 or FGFR4. We isolated MAbs that bound to paraffin embedded tissue and
      immunoblots of recombinant receptor. These epitope-defined MAbs can distinguish
      between members of the FGF receptor family and should be useful as tools for
      assessing FGF receptor expression in a variety of normal and diseased tissues.

PMID- 9523235
TI  - Characterization of a unique anti-DNA hybridoma.
AB  - We have previously described the isolation and in vitro binding properties of
      eight anti-DNA monoclonal antibodies (MAbs) from an MRL-lpr mouse. In light of
      recent reports that have indicated it is possible to isolate multiple MAbs from a
      single hybridoma, our pathogenic hybridoma, 11F8, was examined for evidence of
      similar phenomena. Chromosome counting suggested that 11F8 cells are unusual and
      might indeed be expressing multiple heavy and/or light chains. PCR, cloning, and
      sequencing of immunoglobulin heavy and light chains indicate that 11F8 displays
      expression of both gamma 2a and gamma 3 heavy chains at the DNA level. Flow
      cytometry and amino acid sequencing reveals that expression of multiple isotypes
      also occurs at the protein level but only a single heavy- and light-chain
      sequence is able to bind DNA. Based on these results, we conclude that 11F8 is an
      unusual hybridoma that secretes two distinct heavy and at least one light chain
      from a single cell, and may represent a trioma, a stable three-cell fusion.

PMID- 9523236
TI  - Differential effects of immunosuppressants and antibiotics on human monoclonal
      antibody production in SCID mouse ascites by five heterohybridomas.
AB  - SCID mice were inoculated with five human-mouse heterohybridomas derived by
      fusion of human lymph node lymphocytes from lung cancer patients with murine
      myeloma cells or human-mouse heteromyeloma cells, and the production of their
      human monoclonal antibodies (MAb) in the mouse ascites was investigated. In a
      comparison of the effects of pretreatment by i.p. (intraperitoneal) injection of
      pristane and anti-asialo GM1 serum on the antibody production of three of the
      hybridomas, pristane pretreatment resulted in substantial antibody production by
      all three, and pretreatment with anti-asialo GM1 serum resulted in similar or
      slightly lower levels of antibody production by two of the hybridomas but none by
      the third. In a second series of experiments using four of the hybridomas with
      pristane pretreatment, the co-injection of either penicillin G and streptomycin
      or kanamycin together with the hybridoma at the time of i.p. inoculation resulted
      in enhanced MAb production by the two heterohybridomas that had been propagated
      in medium containing hypoxanthine-aminopterin-thymidine (HAT) but not by the two
      that had been propagated in HAT-free medium.

PMID- 9523237
TI  - Monitoring of PPAR alpha protein expression in human tissue by the use of PPAR
      alpha-specific MAbs.
AB  - We report the production and characterization of two PPAR alpha subtype-specific
      monoclonal antibodies raised against the N-terminal domain of PPAR alpha. P alpha
      b 11.80A is a Western-reactive antibody, whereas P alpha b 32.51 is useful for
      immunohistochemistry. Both antibodies exhibited high affinity against the
      immunogen based on BIAcore analysis, recognized full-length PPAR alpha protein in
      PPAR alpha-transfected CV-1 cells, and displayed no cross-reactivity against the
      N-terminal domains of PPAR gamma or PPAR delta proteins as demonstrated by
      various immunoassays. The application of these antibodies to a panel of normal
      human tissues revealed that PPAR alpha protein expression is highest in skeletal
      muscle, liver, and kidney, consistent with previously reported mRNA expression
      data. These antibodies provide us with valuable tools to further explore the
      function of PPAR alpha.

PMID- 9523238
TI  - Five monoclonal antibodies against glycophorin A of human erythrocyte recognize
      glycoprotein of bovine erythrocyte.
AB  - To study heterophile blood antigens on erythrocytes between human and
      experimental or domestic animals, we have produced 295 monoclonal antibodies
      (MAbs) to human erythrocyte membrane protein. According to the affinity,
      reactivity, and titre of the MAbs, we selected 40 clones to study the heterophile
      blood antigens between human and bovine, chicken, guinea pig, horse, rabbit,
      sheep, and swine. Five MAbs commonly reacted with human type A, type B, and type
      O erythrocytes and reacted with bovine erythrocytes as well but did not react
      with erythrocytes from other species. Other MAbs did not react with erythrocytes
      from all the tested animals. These five MAbs reacted with the same erythrocyte
      membrane protein, 90 KD glycophorin A (GPA) of human or 200 KD major glycoprotein
      and other two components of bovine by immunoblotting and GPA competitive
      inhibition assay. Furthermore, by enzyme treatment and monosaccharide competitive
      inhibition assay, it was confirmed that these five MAbs recognized antigen
      epitope of glycosylation free amino acid portion but not glycosylation portion of
      GPA of erythrocyte membrane.

PMID- 9523239
TI  - Production and characterization of a monoclonal antibody against mannose
      sensitive hemagglutinin of Vibrio cholerae.
AB  - We have generated murine monoclonal antibodies (MAb) against Vibrio cholerae
      mannose-sensitive hemagglutinin (MSHA) using conventional hybridoma procedures.
      Seven hybridomas were obtained and one characterized. Hybridoma 2F12/F1 secreted
      an antibody of the IgG3 type that reacted with a 17-kDa antigen corresponding to
      the product of the mshA gene. This MAb inhibited mannose-sensitive agglutination
      of chicken erythrocytes by EL tor and O139 vibrios. Vibrios expressing MSHA
      activity inhibited binding of the antibody secreted by 2F12/F1 to MSHA-coated
      microtiter plates.

PMID- 9523240
TI  - Generation of murine monoclonal antibodies in serum-free medium.
AB  - Traditional hybridoma fusion technology requires complete medium with serum
      supplements to support the growth of hybridoma cells. Serum is also required for
      subcloning of hybridoma cells to support low density cell growth. IL-6 has been
      shown to enhance the growth of hybridomas and stimulate antibody production by B
      cells. We found that the serum requirement in media used for generation of
      hybridomas can be totally eliminated by substituting with 300 units/ml of IL-6.
      Stable hybridoma cell lines were generated to peptide and protein antigens using
      serum-free adapted P3.653 myelomas as the fusion partner and medium containing IL
      6. Our results indicate that, in general, the fusion efficiencies of serum-free
      IL-6 supplemented fusions are lower than the fusions employing serum containing
      media (40%-60% vs. 80%-100%). However, in spite of the lower fusion efficiency,
      the number of antigen-specific clones generated using IL-6 was equal to or
      greater than fusions using serum supplements. The use of IL-6 instead of serum in
      the generation of monoclonal antibodies (MAbs) has several advantages. We are
      able to eliminate the costly need for serum in media by using IL-6 that is
      prepared in house. In addition, we eliminate the need for time-consuming serum
      free adaptation of hybridoma cell lines prior to transfer to hollow fiber
      bioreactors.

PMID- 9523241
TI  - Random expression of human immunodeficiency virus-1 (HIV-1) p17 (epitopes) on the
      surface of the HIV-1-infected cell.
AB  - Twenty monoclonal antibodies (MAbs) were obtained by immunizing Balb/c mice with
      recombinant p17 (rp17) of HIV-1. Epitope specificity of each MAb was determined
      using six peptides that cover the entire region of p17. We found that each MAb
      reacts with only one of the peptides, residues 12-29, 30-52, 53-87, and 87-115
      (P12-29, P30-52, P53-87, P87-115) of p17 with the exception of one MAb. Three
      kinds of MAbs that recognize P30-52, P87-115, and a conformational epitope,
      suppressed the infectivity of HIV-1 (JMH-1) when they added in the culture of MT
      4 cells infected by HIV-1 within 24 h of the infection.

PMID- 9523242
TI  - Occupational and environmental medicine in Denmark.

PMID- 9523243
TI  - Risk for hand eczema in employees with past or present atopic dermatitis.
AB  - Persons with atopic dermatitis run a considerable risk of developing hand eczema
      when exposed to occupational agents that are a burden to the skin. This also
      pertains to those with a history of skin atopy in childhood. This review presents
      estimates of the risk of developing hand eczema and examines the evidence for an
      effect modification by skin atopy on exposure. Skin atopy at least doubles the
      effects of irritant exposure and, thus, doubles the risk in occupations where
      hand eczema is a common problem. On the basis of this evidence, guidelines for
      occupational counseling can be given. Further development of a scale indicating
      the degree of atopic skin diathesis should facilitate the targeting of this
      counseling toward specific high-risk groups.

PMID- 9523244
TI  - Ambient and biochemical effect monitoring of workers exposed to ethylene oxide.
AB  - OBJECTIVES: Ethylene oxide is an alkylating agent known to be a directly acting
      mutagen and carcinogen. This study describes the relationship between workplace
      ambient air concentrations of ethylene oxide and the concentration of N-2
      hydroxyethylvaline in the globin of exposed workers. METHODS: During the
      sterilization of medical equipment, 12 workers were occupationally exposed to
      ethylene oxide. Personal and stationary ambient air measurements were carried out
      to monitor the external exposure. The determination of the protein adducts was
      based on the N-alkyl-Edman method, introducing a new commercially available
      dipeptide standard for calibration purposes. RESULTS: Ethylene oxide
      concentrations ranging from 0.2 to 8.5 ppm were found in the workplace air. The
      adduct concentrations ranged from 5,219 to 32,738 pmol N-2-hydroxyethylvaline/g
      globin in the case of regularly exposed workers (n = 9) and from 518 to 3,321
      pmol N-2-hydroxyethylvaline/g globin for three persons with occasional contact
      with ethylene oxide. CONCLUSIONS: The Deutsche Forschungsgemeinschaft established
      in 1993 a relationship between the ethylene oxide concentration in ambient air
      and the amount of N-2-hydroxyethylvaline in human globin. By extrapolation,
      constant exposure to 1 ppm ethylene oxide should yield approximately 4,000 pmol N
      2-hydroxyethylvaline/g globin. The ambient air concentrations of ethylene oxide
      and the amount of N-2-hydroxyethylvaline determined within the present study
      confirm this extrapolation in practice. In addition, the determination of adducts
      based on the use of commercially available dipeptide standards for calibration
      purposes turned out to be an advantageous alternative to the commonly used
      protein standards.

PMID- 9523245
TI  - Interleukin 1 alpha hematological examination in mechanics exposed to low benzene
      concentrations.
AB  - OBJECT: To examine the hypothesis of Renz and Kalf relative to the involvement of
      interleukin 1 alpha (IL-1 alpha) in the development of anemia in benzene-exposed
      workers. According to this hypothesis, benzene inhibits the cleavage of the IL-1
      alpha precursor (proIL-1 alpha) to mature IL-1 alpha and the lack of this
      cytokine is responsible for benzene-induced bone marrow suppression. This
      inhibition of the processing of proIL-1 alpha is attributed to an inhibition of
      calpain. METHOD: Selection of a population of mechanics exposed to low levels of
      benzene from fuels, assessment of usual exposure and lifetime exposure duration,
      and measurements of concentrations of workplace-air benzene and urinary benzene
      metabolites. Determination of IL-1 alpha concentrations was done by a whole-blood
      assay after lipopolysaccharide stimulation and a hematological examination was
      carried out. Statistical analysis considered several possible confounding
      factors, particularly smoking and drinking habits. DESIGN: Cross-sectional study.
      RESULTS: The level of exposure of the mechanics to benzene from fuels was mostly
      well below 1 ppm. IL-1 alpha production was not decreased in mechanics exposed to
      benzene from fuels, and no correlation between IL-1 alpha concentrations and red
      blood cell counts appeared. With the exception of a slight decrease in red blood
      cell counts in mechanics, no hint of a toxic effect of exposure on hematological
      parameters was found. CONCLUSIONS: The hypothesis of Renz and Kalf could not be
      confirmed. Although the low level exposure of the study population and
      methodological factors are possible explanations, it cannot be excluded that the
      hypothesis of Renz and Kalf is not generalizable to benzene-exposed humans.
      Presently, one cannot advise the measurement of IL-1 alpha production for
      biological effect monitoring of workers exposed to low concentrations of benzene.

PMID- 9523246
TI  - Vibration sense in the upper limb in patients with repetitive strain injury and a
      group of at-risk office workers.
AB  - OBJECTIVES: To investigate in patients with repetitive strain injury (RSI) and in
      office workers using computer keyboard equipment (a) whether the vibration
      threshold in the hand was altered, (b) the immediate effects of keyboard use on
      vibration thresholds and (c) whether the tolerance of suprathreshold vibration
      was normal. METHOD: A vibrametre (Somedic Ab, Stockholm Sweden) was used to
      obtain threshold vibration measurements, by the method of limits, for all
      peripheral-nerve cutaneous distributions in the hand. Tolerance of suprathreshold
      stimulation was obtained by stimulation of the soft tissues of the forearm by
      increasing the amplitude of vibration. RESULTS: Thresholds for vibration were
      significantly raised for the median nerve in both the patient and office-worker
      groups. The patient group additionally had raised thresholds for the ulnar nerve.
      Following use of the keyboard, thresholds for the median nerve were further
      elevated in the patient group, but not in the other groups, demonstrating a work
      related exacerbation. At suprathreshold stimulation. 14 members (82%) of the
      patient group experienced an allodynic response to vibration, indicating,
      possible changes in the central processing of non-noxious sensory information.
      This changed sensory response was not seen in either the office-worker or control
      groups. CONCLUSION: Patients may have a minor polyneuropathy, whereas the office
      workers demonstrate early signs of the condition. Quantitative measurement of
      vibration perception may prove useful in patient assessment and for detection of
      the early onset of RSI in the work environment.

PMID- 9523247
TI  - Albumin and hemoglobin adducts as biomarkers of exposure to styrene in fiberglass
      reinforced-plastics workers.
AB  - OBJECTIVE: The purpose of this work was to compare levels of styrene-7,8-oxide
      (SO) adducts of albumin (Alb) and hemoglobin (Hb) with those of two urinary
      metabolites of styrene, mandelic acid (MA) and phenylglyoxylic acid (PGA), among
      workers exposed to styrene in the reinforced-plastics industry and in unexposed
      subjects. We also wished to determine whether cigarette smoking influenced adduct
      levels among these subjects. METHODS: A group of 22 male workers was selected on
      basis of an expectedly high level of exposure to styrene, and a group of 15
      controls was selected from hospital blood donors and hospital staff. In the
      exposed group, MA and PGA were quantified by high-performance liquid
      chromatography (HPLC) analysis of urine samples collected prior to the work
      shift. The SO adducts were cleaved from cysteine residues by reaction with Raney
      nickel to give 1-phenylethanol (1-PE) and 2-phenylethanol (2-PE), which, after
      derivatization, were measured using gas chromatography-mass spectrometry (GC-MS)
      in the negative-chemical-ionization (NCI) mode. RESULTS: The estimated mean
      levels of MA and MA + PGA were 74 and 159 mg/g creatinine, respectively. Using
      the levels of urinary metabolites, an average styrene concentration of about 100
      mg/m3 in the workplace air was estimated. The mean levels of 2-PE and 1-PE
      adducts in exposed workers were 2.84 and 0.60 nmol/g Alb and 5.44 and 0.43 nmol/g
      Hb, respectively. When subjects were stratified by level of urinary metabolites
      [zero (controls), low-level exposure (MA + PGA < or = 159 mg/g creatinine), and
      high-level exposure (MA + PGA > 159 mg/g creatinine)] and smoking status (smokers
      versus nonsmokers), a difference in Alb adduct levels was found among the groups
      (2-PE P = 0.002, I-PE P = 0.052). The difference in 2-PE-Alb levels was related
      to exposure category, to smoking status, and to their interaction. Correlations
      at or near a 0.05 level of significance were observed among the workers (n = 22)
      between individual levels of SO-protein adducts and MA + PGA (2-PE Alb, r = 0.54,
      2-PE Hb, r = 0.40). CONCLUSION: Our data suggest that only exposure to relatively
      high levels of styrene allows a clear relationship to be detected between styrene
      exposure and SO adducts, due in part to the effects of cigarette consumption and
      to the high background levels of these adducts observed in unexposed subjects.

PMID- 9523248
TI  - Low-level arsenic excretion in breast milk of native Andean women exposed to high
      levels of arsenic in the drinking water.
AB  - OBJECTIVE: To investigate the excretion of arsenic in breast milk of lactating
      native Andean women living in a village in northwestern Argentina with high
      concentrations of arsenic in the drinking water (about 200 micrograms/l) and to
      assess the exposure of children to arsenic during the very first period of life.
      METHODS: The study included ten lactating women and two nursing babies. Hydride
      generation atomic absorption spectrometry (HG-AAS) was used to determine the
      concentration of arsenic in samples of human milk, drinking water, blood, and
      urine. RESULTS: The concentrations of arsenic detected in maternal blood (total
      arsenic) and urine (metabolites of inorganic arsenic) were high, averaging 10 and
      320 micrograms/l, respectively. In subjects without known exposure to arsenic the
      average concentrations found in blood and urine are 1-2 and about 10
      micrograms/l, respectively. The metabolites of inorganic arsenic constituted more
      than 80% of the total arsenic in the urine, which shows that inorganic arsenic
      was the main form of arsenic ingested. The average concentration of arsenic
      detected in human milk was 2.3 micrograms/kg fresh weight (range 0.83-7.6
      micrograms/kg). Although data on background levels of arsenic in human breast
      milk are scarce, the present concentrations seem to be slightly elevated.
      However, considering the high levels of arsenic exposure in the mothers, the
      total arsenic concentrations measured in human milk were low. In concordance with
      the low concentrations of arsenic found in the milk, the concentrations of
      arsenic metabolites measured in the urine of two of the nursing babies were low:
      17 and 47 micrograms/l, respectively. CONCLUSIONS: The low concentrations of
      arsenic detected in the breast milk and urine of the two nursing babies in
      relation to the high level of maternal exposure to arsenic indicate that
      inorganic arsenic is not excreted in breast milk to any significant extent. This
      is a very important reason for long breast-feeding periods.

PMID- 9523249
TI  - Effects on the kidney of occupational exposure to styrene.
AB  - OBJECTIVES: To elucidate the extent of nephrotoxicity of long-term occupational
      exposure to styrene. METHODS: In all 10 styrene-exposed workers (employed, mean
      age 12.6 years) and 15 nonexposed workers were studied. Each participant
      collected multiple overnight and end-of-shift urine samples. The sum of the
      urinary concentrations of mandelic acid and phenylglyoxylic acid (MAP) was
      determined to assess the absorbed dose of styrene. The urinary parameters alanine
      aminopeptidase (AAP), beta-galactosidase (beta GAL), N-acetyl-beta-D
      glucosaminidase (NAG), retinol-binding protein (RBP), and albumin (ALB) were
      determined to assess the effects on renal function and integrity. RESULTS: The
      median concentration of MAP in urine was 175 mg/g urinary creatinine (CREAT-U;
      range 72-496 mg/g). The 8-h time-weighted average (8-h TWA) exposure to styrene
      was estimated from the urinary concentration of MAP and ranged from 21 to 405
      mg/m3. RBP showed a borderline correlation with the dose of styrene. ALB in end
      of-shift urine samples showed a borderline correlation with the absorbed dose of
      styrene. CONCLUSIONS: From the borderline correlation of RBP with the dose of
      styrene it was concluded that there might be a slight effect on the tubuli. The
      borderline correlation of ALB with the dose of styrene, together with the
      observation that five values were above the reference limit of the laboratory,
      suggests an effect on this parameter.

PMID- 9523250
TI  - Occurrence of occupational asthma in aluminum potroom workers in relation to
      preventive measures.
AB  - The purpose of this study was to investigate whether preventive measures such as
      reduction of exposure and the introduction of the histamine provocation test
      (HPT) as a selection instrument resulted in a lower incidence of potroom asthma
      (PA) and a longer time lag between the commencement of employment and the
      occurrence of PA. Between 1970 and 1990, 179 cases of PA were diagnosed. This
      period was divided into three periods. During period 1 (1970-1975), no exposure
      data were available. Period 2 (1976-1981) is characterized by known exposure data
      obtained by means of fluoride determinations in urine. At the beginning of period
      3 (1982-1990) the HPT was incorporated into the preemployment medical
      examination. We computed the incidence density (ID) in the three periods and
      analyzed the timelag in relation to the year of employment and confounding
      factors such as age, atopic history, blood eosinophil counts, lung function,
      smoking habits at preemployment, and exposure level. After introduction of the
      preemployment HPT the ID decreased, but cases continued to occur (ID 11.6 in
      period 2 versus 2.5 in period 3). The time lag was did not differ when subjects
      with bronchial hyperresponsiveness were screened out. The exposure level and an
      atopic history were factors associated with the period of employment and,
      therefore, confounded the results. The results of this study support the role of
      an atopic history as a risk factor for development of PA at lower exposure levels
      and suggest that potroom exposure not only incites asthmatic symptoms but also
      acts as an inducer of respiratory disease.

PMID- 9523251
TI  - Exposure to cobalt and nickel in the hard-metal production industry.
AB  - OBJECTIVE: The shortage of cobalt (Co) on the metal market forced the industry to
      add nickel (Ni) to Co as a binding agent for the sintering of hard metal. This
      change enabled us to study (1) the exposure to Ni powder and (2) the effect of Ni
      on Co uptake (and vice versa). METHODS: Equal amounts of Co and Ni were used in
      the mixture in a plant employing 50 workers. Both personal ambient-air samples
      and single-void urine samples were taken twice in the same week, i.e., on Monday
      and Thursday. Atomic absorption spectroscopy (AAS) was used for analyses.
      RESULTS: The airborne availability of Ni (mean value 41.65 +/- 6.29
      micrograms/m3) was 2-fold that of Co (mean value 21.85 +/- 24.25 micrograms/m3),
      although the two series of data (n = 20) were significantly correlated. Even if
      the Co and Ni urinary concentration values (n = 45) recorded on Monday morning
      and Thursday evening were significantly correlated, at the end of the week there
      was a 3-fold increase, specifically, from 7.3 to 22.28 micrograms/l, in Co
      elimination (a significant difference) and a 30% increase in Ni elimination from
      11.98 to 15.83 micrograms/l. Moreover, on Monday morning, 90% of Ni urinary
      concentration values were higher than those of Co as opposed to only 33% on
      Thursday evening. In the six cases in which both airborne and urine
      determinations were performed on the 2 days, no significant relationship was
      found between external exposure and biological monitoring data. CONCLUSIONS:
      Although Ni uptake was variable, it was generally low, whereas Co uptake was
      substantial, as had previously been observed in the same plant when Co was the
      only binder under use. It was therefore possible to rule out any influence of Ni
      exposure on Co uptake and to suggest the contrary, as has been demonstrated in
      bacterial species and in rats using everted intestinal sacs.

PMID- 9523252
TI  - Medical surveillance programs in Germany.

PMID- 9523253
TI  - Synthesis of a one-bead one-compound combinatorial peptide library.

PMID- 9523254
TI  - Enzyme-linked colorimetric screening of a one-bead one-compound combinatorial
      library.

PMID- 9523255
TI  - Synthesis and screening of positional scanning combinatorial libraries.

PMID- 9523256
TI  - Synthesis and screening of peptide libraries on continuous cellulose membrane
      supports.

PMID- 9523257
TI  - Peralkylation. "Libraries from libraries": chemical transformation of synthetic
      combinatorial libraries.

PMID- 9523258
TI  - Introduction to combinatorial solid-phase assays for enzyme activity and
      inhibition.

PMID- 9523259
TI  - Preparation of biocompatible resins for library syntheses.

PMID- 9523260
TI  - Intramolecular fluorescence-quenched substrate libraries.

PMID- 9523261
TI  - The solid-phase enzyme inhibitor library assay.

PMID- 9523263
TI  - The use of peptide library for the determination of kinase peptide substrates.

PMID- 9523262
TI  - Determination of peptide substrate motifs for protein kinases using a "one-bead
      one-compound" combinatorial library approach.

PMID- 9523264
TI  - Analysis of protein kinase substrate specificity by the use of peptide libraries
      on cellulose paper (SPOT-method).

PMID- 9523265
TI  - Generation of multiuse peptide libraries for functional screenings.

PMID- 9523266
TI  - Functional screening of multiuse peptide libraries using melanophore bioassay.

PMID- 9523267
TI  - The basic structure of filamentous phage and its use in the display of
      combinatorial peptide libraries.

PMID- 9523268
TI  - Construction and use of a 20-mer phage display epitope library.

PMID- 9523269
TI  - Construction of disulfide-constrained random peptide libraries displayed on phage
      coat protein VIII.

PMID- 9523270
TI  - Conformational mimicry through random constraints plus affinity selection.

PMID- 9523271
TI  - The use of combinatorial libraries to identify ligands that interact with surface
      receptors in living cells.

PMID- 9523272
TI  - Screening phage display peptide libraries on nitrocellulose membranes.

PMID- 9523273
TI  - Identification of disease-specific epitopes.

PMID- 9523274
TI  - Identification of peptide ligands for the antigen binding receptor expressed on
      human B-cell lymphomas.

PMID- 9523275
TI  - Major histocompatibility complex allele-specific peptide libraries and
      identification of T-cell mimotopes.

PMID- 9523276
TI  - Phage display of peptide libraries on protein scaffolds.

PMID- 9523277
TI  - Displaying libraries of conformationally constrained peptides on the surface of
      Escherichia coli as flagellin fusions.

PMID- 9523278
TI  - Combinatorial peptide library as an immunogen.

PMID- 9523280
TI  - Effect of aging on the tumoricidal functions of murine peritoneal macrophages.
AB  - The present investigation was carried out to study the effect of aging on the
      activation of murine peritoneal macrophages by lipopolysaccharide (LPS) plus
      interferon-gamma (IFN-gamma) to tumoricidal state. Age-dependent alteration in
      macrophage-mediated tumor cell binding, cytotoxicity, cytostasis and production
      of the tumoricidal effector molecules oncostatin M, tumor necrosis factor and
      nitric oxide (NO) was studied. Macrophages (1.5 x 10(5)) obtained from mice of
      different age groups were separated on the basis of the reproductive status of
      the mice into prereproductive (young), reproductive (adult) and postreproductive
      (old) for studying their activation. Macrophages obtained from the old mice were
      found to be least responsive to the activation signal of LPS + IFN-gamma for
      macrophage-mediated tumoricidal activity and production of effector molecules.
      The macrophages of the old mice did not express inducible nitric oxide synthase,
      an enzyme responsible for the production of NO by activated macrophages.
      Macrophages of the adult and young groups showed better response; however,
      optimal response was observed in the macrophages of adult mice. The reasons for
      the observed difference in the response of macrophages are discussed.

PMID- 9523279
TI  - Human interleukin-2-activated adherent natural killer cells recognize a conserved
      antigen found on tumor cells and protozoan parasites.
AB  - Plastic adherent interleukin-2-activated human natural killer (NK) cells (ALAK)
      lyse many different histological types of tumor target cells. In order to effect
      their function as cytotoxic mediators of innate immunity, ALAKs may 'recognize'
      antigen(s) of protozoan parasites, select virus-infected cells and they may
      release certain cytokines in response to bacterial antigens. In the present
      study, we demonstrate that CD3-/CD56dim/CD16dim/monoclonal antibody 5C6bright
      human ALAKs bind to an antigenic determinant on tumor cells independent of target
      cell H-2 allotype expression. The conserved antigen was originally obtained from
      the protozoan Tetrahymena pyriformis, however it is also located on the membranes
      of many ALAK-sensitive tumor cells. The sequence of this protein, i.e. NK target
      antigen/NKTag, was previously deduced from cDNA. One ALAK cognate determinant of
      NKTag was identified by inhibition of cytotoxicity using NKTag-derived synthetic
      peptides. Biotinylated synthetic peptide [amino acids (aa) 58-74] bound to ALAKs,
      and synthetic peptides corresponding to this sequence inhibited ALAK lysis of
      U937 target cells. Inhibition effects of peptide binding were nonreversible. To
      determine the requirements for recognition by ALAKs of this antigenic
      determinant, the cognate peptide aa 55-74 was truncated to 17-, 14-, 10-, 7- and
      6-mer lengths and tested for inhibition of cytotoxicity. All inhibited except the
      6-mer. A possible mechanism of peptide inhibition of cytotoxicity following ALAK
      binding to an antigenic determinant was a requirement for recognition of one
      anchor peptide (arginine) and receptor occupancy by a minimum of five to six
      additional amino acids. In antibody-dependent cell-mediated cytotoxicity
      experiments, synthetic peptide (aa 68-74) inhibited ALAK killing of anti-H-2d
      sensitized P815 targets. This same peptide also inhibited conventional lysis of
      nonsensitized P815 and IM-9 targets. However, the cognate synthetic peptide (aa
      58-74) did not inhibit conjugate formation between ALAKs and U937 target cells.
      These data demonstrate that ALAK binding to a soluble monomeric peptide inhibited
      cytotoxicity. Peptide binding appeared to negatively regulate cytotoxicity, and
      the inhibitory effects following peptide binding were nonreversible.
      Effector:target cell conjugate formation was not affected by peptide binding,
      however, recognition was required because inhibition was specific for the amino
      acid sequence of the synthetic peptide.

PMID- 9523282
TI  - Bcl-2 is expressed in human natural killer cells and is regulated by interleukin
      2.
AB  - Bcl-2 is a major anti-apoptotic protein expressed in many normal and malignant
      cells. Recently, low to absent expression was reported in human natural killer
      (NK) cells cultured in serum-free media which could be induced with stem cell
      factor. We investigated the expression of bcl-2 protein of NK cells in normal
      blood donors and compared the bcl-2 expression in CD56+ NK cells with CD3+ T
      cells. To determine bcl-2 reactivity, a three-color flow-cytometric technique was
      used. CD56+ CD3- NK cells had an average bcl-2 expression of 83% compared with
      CD3+ T cells. CD56 and CD3 double positive T cells had an average content of 111%
      compared with all peripheral CD3+ T lymphocytes. When peripheral mononuclear
      cells were cultured with interleukin-2 (IL-2), bcl-2 could be upregulated by IL-2
      in all cell populations studied. The induction of bcl-2 in these cell populations
      paralleled the induction in CD56- T lymphocytes cultured under identical
      conditions. The induction of bcl-2 by IL-2 was confirmed by Western blotting. The
      maximum induction of bcl-2 by IL-2 was observed at an IL-2 dose of 100-1,000
      U/ml. Our data confirm the anti-apoptotic protein bcl-2 as an activation- or
      proliferation-associated marker of normal NK cells which can be induced by IL-2.

PMID- 9523283
TI  - The eye within the framework of human senescence: biological decline and
      morbidity.
AB  - An introduction to basic risk theory is applied to an analysis which is used to
      calculate risks for mortality, age-related maculopathy, and nuclear cataract. A
      number of ad hoc assumptions are introduced, and the predicted results compared
      with results culled from the literature. The results for nuclear cataract
      indicate that the loss of life expectancy associated with this condition may
      exceed 3 years. Finally, the theory is applied to an estimate of general
      blindness.

PMID- 9523281
TI  - A natural immunity-activating plant lectin, Viscum album agglutinin-I, induces
      apoptosis in human lymphocytes, monocytes, monocytic THP-1 cells and murine
      thymocytes.
AB  - A galactoside-specific plant lectin, Viscum album agglutinin-I (VAA-I) with
      protein synthesis-inhibiting properties, has been shown to be cytotoxic in
      various eukaryotic cells, in vitro above a 10 ng/ml concentration. Noncytotoxic
      concentrations of VAA-I induced mRNA expression and enhanced secretion of
      proinflammatory cytokines in cultures of human peripheral blood mononuclear
      cells. In an animal model VAA-I has been shown to stimulate natural killer cells
      and granulocytes. In this study, human peripheral blood lymphocytes (PBL), human
      peripheral blood monocytes (PBM), murine thymocytes and human monocytic THP-1
      cells were incubated for 24 h in the presence of various concentrations of VAA-I.
      The apoptotic effect of VAA-I was analyzed by flow cytometry following staining
      of the apoptotic nuclei in the cells with PI in hypotonic buffer and quantitative
      detection of DNA breaks were analyzed by the terminal deoxynucleotidyl
      transferase-mediated dUTP-digoxigenin nick end-labeling (TUNEL) assay. In
      cultures of all types of investigated cells, a dose-dependent VAA-I
      concentrations above 10 ng/ml in PBL and at 1 ng/ml VAA-I concentration in PBM,
      thymocytes and THP-1 cells, a lectin-induced increase of the apoptotic nuclei was
      observed. In 24-hour cultures of PBL and thymocytes, the ratios between apoptotic
      and nonapoptotic cells were enhanced 10 times and 8 times, respectively, by 100
      ng/ml VAA-I compared to the negative control. The concentration of 100
      micrograms/ml VAA-I only caused necrosis. The isolated A chain of the VAA-I
      induced apoptosis in PBL and thymocytes. In the culture of PBL the isolated B
      chain of the VAA-I was not effective indicating that cytokine induction by VAA-I
      is probably not involved in its apoptotic effect. On CD4+8+ thymocytes, VAA-I
      resulted in a reduced expression of CD8+ molecules that could be related to a
      loss of volume and increase of density, both characteristic features of
      apoptosis.

PMID- 9523285
TI  - Does light stimulus at eye opening of the developing rat influence retinal
      expression of GTP-binding protein (G(0))?
AB  - We previously hypothesized that light stimulus at eye opening of rats on
      postnatal days (P) 13 or 14 has an effect on the expression of GTP-binding
      proteins (G(0) in the retina) because the concentration of G(0) alpha increased
      rapidly between P10 and P15. This hypothesis was also supported by the findings
      that the distribution of G(0) alpha in the retina was almost the same as that of
      adult rats between P10 and P15. In this study, pregnant rats were kept in a dark
      room after vaginal plugs were identified; they gave birth to their pups in the
      dark, and their pups were reared by their mothers in the dark. The postnatal rats
      were sacrificed at P10, P15, P18, P22, P24, P27, and P30. Their retinas were
      investigated immunochemically and immunohistochemically, using G(0) alpha
      antibody, and these results were compared with those of the rat pups reared
      normally. Only G(0) alpha immunoreactivity in the inner nuclear layer of rats
      reared in the dark room was weaker than in the controls; the distribution of G(0)
      alpha in the retina did not change, as compared with pups reared in normal
      conditions. In addition, in pups reared in the dark, G(0) alpha increased rapidly
      from P10 to P15. However, the concentration of G(0) alpha in the retina of rat
      pups reared in the dark was significantly low at P22 (p < 0.01) and P30 (p <
      0.05), as compared with pups reared in normal conditions. Although the function
      of G(0) in the retina may have something to do with the light stimulus after eye
      opening, it appeared that the expression of G(0) was not influenced by light
      stimulus at eye opening.

PMID- 9523284
TI  - Gene expression of the phosducin-like protein in the retina.
AB  - Phosducin, which is expressed abundantly in the retina, mediates
      phototransduction or signal transduction cascades by interacting with transducin
      or G-protein beta gamma-subunits. We have reported on the possibility that
      phosducin is expressed from a multiple gene family and that each phosducin may
      mediate G-protein-coupled signal transduction cascades. To elucidate new genes
      that may mediate signal transduction cascades in the retina and that may form a
      gene family with phosducin, we screened a bovine retinal cDNA library. During the
      screening, we identified a cDNA that looked the same as the phosducin-like
      protein of the rat, as reported by other investigators. We examined the gene
      expression in rat retina using semiquantitative polymerase chain reaction and
      compared it to that of other organs. One form generated by alternative splicing
      expressed in the retina was the same as in other tissues, but, interestingly,
      another form had differing tissue distribution and was expressed abundantly in
      the retina.

PMID- 9523286
TI  - Pattern electroretinogram elicited by a dartboard pattern.
AB  - The receptive field size of retinal ganglion cells is closely related to their
      eccentricity from the fovea. To elicit larger pattern-reversal electroretinograms
      (P-ERGs), it may be useful to stimulate the retina with patterns having elements
      that parallel this change in receptive field size. We describe a dartboard
      pattern consisting of reversal elements that enlarge gradually from the central
      to the peripheral stimulus field. The utility of the dartboard pattern for
      eliciting P-ERG was investigated by comparing it with the conventional uniform
      checkerboard pattern, but with the other stimulus parameters remaining unchanged
      (96% contrast, 35.9 cd/m2 mean luminance, 3.3 rev/s temporal frequency, 15
      degrees circular field). The dartboard pattern produced a significantly larger
      P50 amplitude than did the checkerboard pattern, while no difference in peak
      latency was found when 54 min of arc was used as a standard check size for the
      checkerboard pattern. The dartboard pattern for eliciting P-ERG should prove
      clinically useful.

PMID- 9523287
TI  - Effect of topical Na-hyaluronan on hemidesmosome formation in n-heptanol-induced
      corneal injury.
AB  - The present study investigated the effect of Na-hyaluronan (Na-HA) on the
      hemidesmosome morphogenesis in n-heptanol-induced corneal wounds. Central
      epithelial wounds were induced in the rabbit cornea by applying a 5.5-mm round
      filter paper, which was soaked in n-heptanol, for 60 s. 1% Na-HA in phosphate
      buffered saline (PBS) or PBS alone were topically administered to the wounded
      cornea 4 times daily for up to 7 days. Epithelial healing rates during the first
      2 days were not altered by Na-HA. The number of hemidesmosomes in the basement
      membrane of the central cornea was significantly increased in both 3- and 7-day
      groups after treatment with 1% Na-HA. The results suggest that topically applied
      1% Na-HA may enhance the formation of hemidesmosomes during the early healing
      phase in n-heptanol-induced corneal wounds.

PMID- 9523288
TI  - Pharmacological evaluation of a new timolol/pilocarpine formulation.
AB  - A new formulation (HYA) based on timolol hyaluronate and pilocarpine hyaluronate
      salts has been shown to improve the bioavailability of the drugs and to extend
      the duration of their action. Extent of the intraocular pressure lowering effect,
      duration of action and aqueous bioavailability of timolol and pilocarpine of HYA
      were compared with a commercial preparation. Ocular hypertension in the rabbit
      was induced by alpha-chymotrypsin or by water loading. The hypotensive effect of
      HYA treatment was significantly greater and longer than that observed in rabbit
      eyes treated with the commercial preparation both in the normotensive and in the
      hypertensive animals. Furthermore, we evaluated the miotic response; due to
      pilocarpine, normotensive rabbits showed a greater miotic response and an
      extended duration when the eyes were treated with HYA. The new formulation
      increased the aqueous availability of timolol and pilocarpine compared to the
      commercial preparation as determined by HPLC. The pharmacodynamic and
      pharmacokinetic profiles of HYA indicate an increase in efficacy and duration of
      action along with an increase in bioavailability of timolol and pilocarpine in
      comparison with the commercial preparation.

PMID- 9523289
TI  - Lenticular calcium, magnesium, and iron levels in diabetic rats and verapamil
      effect.
AB  - Lenticular calcium (Ca), magnesium (Mg), and iron (Fe) changes in diabetic rats
      and the effects of the Ca antagonist drug verapamil on this electrolyte imbalance
      were studied. Verapamil administration had no effect on the blood glucose values.
      Compared to the control group, a significant increase was observed in the
      lenticular Ca, Mg, and Fe content of the diabetic rats. Eight weeks of verapamil
      administration to the diabetic animals significantly reduced lenticular Ca, Mg,
      Fe values. Therefore it is suggested that verapamil might be a useful drug to
      prevent diabetic cataract formation.

PMID- 9523290
TI  - Intracameral levels of intravenously injected fluorescein, cefmenoxime, and
      chloramphenicol in the prostaglandin E2-administered eyes of albino rabbits.
AB  - We evaluated the effects of inflammation and physicochemical nature of selected
      agents on the intracameral levels of intravenously injected drugs in albino
      rabbits. Transcorneal diffusion of prostaglandin E2 (10, 50 or 250 micrograms/ml)
      using a glass cylinder was used to produce inflammation of the anterior segment
      in the right eyes. As a control, a vehicle was applied to the left cornea.
      Immediately, 2, 5, or 11 h after prostaglandin E2 administration, a mixed
      solution of fluorescein, cefmenoxime, and chloramphenicol (50 mg each/kg body
      weight) was injected intravenously. One hour after injection of the drugs, the
      primary aqueous humor was withdrawn. The intracameral levels of protein and these
      drugs after prostaglandin E2 administration increased at 1 h in a dose-dependent
      manner. These levels then gradually decreased. One hour after prostaglandin E2
      administration, the intracameral levels of protein and these drugs in the
      prostaglandin E2-administered eyes were significantly higher than those in the
      vehicle-administered eyes, except chloramphenicol after administration of 10
      micrograms/ml prostaglandin E2. Our findings indicate that the intracameral
      levels of intravenously administered drugs are altered not only by the severity
      of inflammation but also by the properties of drugs.

PMID- 9523291
TI  - Cell growth inhibition and DNA incorporation of mitomycin C in cell culture.
AB  - The present study was performed to clarify the effects of a 4-min exposure of
      mitomycin C (MMC) on cell growth, the cell cycle and MMC dose incorporated into
      DNA, using Chang's cultured human conjunctival cells. A low dose of MMC ranging
      from 0.00025 to 0.004% showed dose-dependent cytotoxicity when cell growth was
      active. Fifty percent cell viability was found when cells were treated with
      0.001% MMC. A flow cytometer showed that 0.001% MMC inhibited the DNA synthetic
      phase. After 0.04% MMC was exposed to 3 x 10(6) cells and immediately rinsed, DNA
      was isolated to measure the dose of MMC detected from DNA. The total amount of
      DNA was 7 micrograms from which 3 micrograms of MMC was detected by high
      performance liquid chromatography. The above results revealed that the lowest
      concentration of MMC which caused 50% cell viability and cell cycle inhibition
      was 0.001% and that MMC was rapidly incorporated into DNA.

PMID- 9523292
TI  - Corneal swelling.

PMID- 9523293
TI  - A pediatrician's view. Earaches.

PMID- 9523294
TI  - Should acute otitis media ever be treated with antibiotics?

PMID- 9523296
TI  - Acute otitis media in the 1990s: the impact of antibiotic resistance.

PMID- 9523295
TI  - The role of inflammatory mediators and anti-inflammatory drugs in otitis media.
AB  - Despite multiple studies, the role of anti-inflammatory drugs in the treatment of
      AOM and OME is unclear. Although the AHCPR was against the use of steroids in
      OME, other studies suggest a possible role with potential cost savings and a
      decrease in the need for surgery in some patients. But the risk-benefit ratio of
      steroid treatment is unclear. There is some evidence that NSAIDs may decrease
      otalgia associated with AOM, but no proof that NSAIDs reduce or prevent
      inflammatory changes in the middle ear associated with AOM and OME.

PMID- 9523297
TI  - The diagnosis and management of otitis media with effusion.

PMID- 9523298
TI  - Preventing otitis media: medical approaches.

PMID- 9523300
TI  - Economics of drug delivery.

PMID- 9523299
TI  - Bioequivalence of topical dermatological dosage forms--methods of evaluation of
      bioequivalence.

PMID- 9523302
TI  - Hydrophobic ion pairing: altering the solubility properties of biomolecules.
AB  - The high aqueous solubility of ionic compounds can be attributed to the ease of
      solvation of the counter ions. Replacement of the counter ions with ionic
      detergents dramatically alters the solubility properties of the molecule. Not
      only does the aqueous solubility drop precipitously, but the solubility in
      organic phases increases as well. Consequently, the partition coefficient changes
      by orders of magnitude. This ion pairing phenomenon, which we term hydrophobic
      ion pairing (HIP), has been extended to polyelectrolytes, such as proteins and
      polynucleotides. These materials form HIP complexes that dissolve in a range of
      organic solvents, often with retention of native structure and enzymatic
      activity. The HIP process has been used to purify protein mixtures, conduct
      enzymatic reactions in nonaqueous environments, increase structural stability,
      enhance bioavailability, and prepare new dosage forms.

PMID- 9523303
TI  - Characterization of frozen aqueous solutions by low temperature X-ray powder
      diffractometry.
AB  - PURPOSE: A low temperature X-ray powder diffractometric (XRD) technique has been
      developed which permits in situ characterization of the solid-state of solutes in
      frozen aqueous solutions. METHODS: A variable temperature stage, with a working
      temperature range of -190 to 300 degrees C, was attached to a wide-angle XRD. The
      stage was calibrated with a sodium chloride-water binary system. RESULTS: When
      aqueous nafcillin sodium solution (22% w/w) was frozen, eutectic crystallization
      of the solute was not observed. However, annealing at -4 degrees C, caused
      crystallization of the solute. With increasing annealing time, there was a
      progressive increase in the crystallinity of the solute. Studies were carried out
      with sodium nafcillin solutions ranging in concentration from 20 to 50% w/w. The
      solid-state of the phase crystallizing from solution was independent of the
      solute concentration. Next, solutions of mono- and disodium hydrogen phosphate
      were individually frozen. Only the latter crystallized as the dodecahydrate
      (Na2HPO4.12H2O). However when an aqueous buffer mixture of mono- and disodium
      hydrogen phosphate was frozen, the former inhibited the crystallization of the
      latter. CONCLUSIONS: Since freezing of solutions is the first step in
      lyophilization, the XRD technique can provide a mechanistic understanding of the
      alterations in solid-state that occur during freeze-drying. DSC has so far been
      the technique of choice to study frozen systems. The advantage of XRD is that it
      not only permits unambiguous identification of the crystalline solid phase(s),
      but it also provides information about the degree of crystallinity. While
      overlapping thermal events are difficult to interpret in DSC, XRD does not suffer
      from such a limitation.

PMID- 9523304
TI  - Interleukin-1 receptor (IL-1R) liquid formulation development using differential
      scanning calorimetry.
AB  - PURPOSE: To elucidate the solution conditions that confer stability of aqueous IL
      1R using differential scanning calorimetry (DSC). METHODS: Optimal pH conditions
      were determined by monitoring degradation products encountered during accelerated
      studies (at elevated temperatures) using SDS-PAGE. At the pH optimum, DSC
      screened for excipients that enhanced thermal stability by shifting the Tm to
      higher values. Using SEC the relationship between thermal unfolding and stability
      was investigated by considering if lower Tm's in the presence of preservatives
      correlated with degradation products at 37 degrees C over time. The degree of
      aggregation relative to that of a control determined the level of stability
      achieved. RESULTS: Circular dichroism (CD) measurements confirmed molecular
      modeling studies showing IL-1R to be about 39% beta-sheet. Two major transitions
      characterized the DSC data with Tm's observed near 47 degrees C and 66 degrees C.
      Among 21 excipients screened, NaCl exhibited the greatest stabilizing influences
      based on shifting the low temperature transition to 53 degrees C. The low
      temperature transition was later found to comprise two transitions, yielding a
      total of three melting transitions for IL-1R. High Tm's arising from the presence
      of preservatives correlated with the order of stability (i.e., 0.065% phenol >
      0.1% m-Cresol > 0.9% benzyl alcohol). CONCLUSIONS: The three melting transitions
      are consistent in origin with the cooperative unfolding of three unique
      immunoglobulin-like domains of IL-1R. Optimal stability was achieved in 20 mM
      sodium citrate at pH 6 with sufficient NaCl to attain the tonicity of human
      serum. A correlation between the predicted ranking of stability and the extent of
      aggregation was demonstrated using DSC.

PMID- 9523301
TI  - DNA methylation as a target for drug design.
AB  - DNA methylation is essential for normal embryonic development. Distinctive
      genomic methylation patterns must be formed and maintained with high fidelity to
      ensure the inactivities of specific promoters during development. The mutagenic
      and epigenetic aspects of DNA methylation are especially interesting because they
      may lead to the inactivation of genes which are involved in human carcinogenesis.
      The mutagenicity of 5-Methylcytosine (5mC) and the role of promoter
      hypermethylation in gene silencing, particularly in cancer, suggest a clinical
      significance for the design of novel DNA methylation inhibitors which may be
      utilized to reverse the effects of DNA methylation.

PMID- 9523305
TI  - pH-metric logP 10. Determination of liposomal membrane-water partition
      coefficients of ionizable drugs.
AB  - PURPOSE: To investigate a novel approach for the determination of liposomal
      membrane-water partition coefficients and lipophilicity profiles of ionizable
      drugs. METHODS: The measurements were performed by using a pH-metric technique in
      a system consisting of dioleylphosphatidylcholine (DOPC) unilamellar vesicles in
      0.15 M KCl at 25 degrees C. The DOPC unilamellar vesicle suspension was prepared
      via an extrusion process. RESULTS: The liposomal membrane-water partition
      coefficients of eight ionizable drugs: ibuprofen, diclofenac, 5-phenylvaleric
      acid, warfarin, propranolol, lidocaine, tetracaine and procaine were determined
      and the values for neutral and ionized species were found to be in the ranges of
      approximately 4.5 to 2.4 and 2.6 to 0.8 logarithmic units, respectively.
      CONCLUSIONS: It has been shown that the liposomal membrane-water partition
      coefficients as derived from the pH-metric technique are consistent with those
      obtained from alternative methods such as ultrafiltration and dialysis. It was
      found that in liposome system, partitioning of the ionized species is significant
      and is influenced by electrostatic interaction with the membranes. We have
      demonstrated that the pH-metric technique is an efficient and accurate way to
      determine the liposomal membrane-water partition coefficients of ionizable
      substances.

PMID- 9523306
TI  - The role of the drug/excipient particle size ratio in the percolation model for
      tablets.
AB  - PURPOSE: In previous papers, a linear relationship between drug particle size and
      drug percolation threshold was found in inert matrix tablets. The main objectives
      of the present work are: to study the influence of the excipient particle size on
      the drug percolation threshold and to investigate if the change in the drug
      percolation threshold is due either to the absolute or to the relative drug
      particle size. METHODS: Matrix tablets have been prepared using KCl (7 different
      particle size fractions) as a drug model and Eudragit RS-PM (4 granulommetric
      fractions) as matrix forming material. In vitro release assays were carried out
      on the 66 lots of tablets. The drug percolation thresholds were estimated
      following the method of Bonny and Leuenberger. RESULTS: The particle size of the
      excipient has shown an opposite effect to the drug size on the drug percolation
      threshold. Nevertheless, the influence of drug and excipient sizes on the drug
      percolation threshold are of the same magnitude. CONCLUSIONS: The drug
      percolation threshold depends linearly on the relative drug particle size. This
      finding is in agreement with percolation theory and can facilitate the use of the
      percolation threshold as a preformulation parameter to improve the pharmaceutical
      dosage forms design.

PMID- 9523307
TI  - Reduced systemic availability of an antiarrhythmic drug, bidisomide, with meal co
      administration: relationship with region-dependent intestinal absorption.
AB  - PURPOSE: The aim of this research was to determine the mechanism by which a co
      administered meal decreases the oral absorption of bidisomide and does not
      influence the oral absorption of the chemically-related antiarrhythmic agent,
      disopyramide. METHODS: Bidisomide plasma levels, following oral administration
      and intravenous infusion in the fasted state and with various meal treatments,
      were determined in human subjects. A dialysis technique was employed to examine
      the potential for drug binding to meal homogenates. Plasma levels, following drug
      administration through duodenal and jejunal intestinal access ports and following
      various meal treatments with oral drug co-administration, were compared for
      bidisomide and disopyramide in a canine model. RESULTS: Bidisomide plasma AUC was
      significantly reduced following oral drug co-administration with breakfast
      compared to fasted-state controls in human subjects and in dogs independent of
      the composition of the solid cooked breakfast. While intravenous bidisomide
      infusion in human subjects showed a statistically significant reduction in AUC 15
      minutes after oral administration of a high fat breakfast as compared to drug
      infusion in the fasted state, the reduction (-13%) was substantially smaller than
      the reduction (from -43% to -63%) observed with oral bidisomide meal co
      administration. The percentages of bidisomide and disopyramide lost by binding to
      homogenates of cooked breakfast were 25.0 +/- 5.7% and 23.7 +/- 7.7%,
      respectively, as determined by dialysis at 4 hours. In dogs, the extent of
      absorption of disopyramide was comparable from oral, duodenal and mid-jejunal
      administration while the extent of bidisomide absorption from mid-jejunal
      administration was significantly lower than for oral or duodenal administration.
      Non-viscous liquid meals decreased Cmax but not AUC, while viscous homogenized
      solid meals decreased both Cmax and AUC for bidisomide with oral drug-meal co
      administration. Oral non-caloric hydroxypropyl methylcellulose meals decreased
      bidisomide to the same extent as homogenized solid meals but did not lower
      disopyramide AUC. CONCLUSIONS: The significant reduction in bidisomide plasma
      levels observed with meal co-administration in human subjects was predominantly
      mediated through a reduction in drug absorption and was independent of solid meal
      composition. The difference in meal effect on the absorption of the two drugs in
      humans did not appear to be a function of drug binding to cooked meal components
      over typical human upper gastrointestinal residence times. In dogs, the high
      viscosity medium generated by oral co-administration of a solid meal reduced the
      upper intestinal absorption of bidisomide and disopyramide. Bidisomide AUC was
      decreased since it was well absorbed in the upper but not lower small intestine.
      Disopyramide AUC was not significantly affected since it was well absorbed from
      both regions. A similar mechanism may play a role in drug plasma level reductions
      following oral co-administration with solid meals for drugs showing similar
      regionally-dependent absorption profiles.

PMID- 9523308
TI  - Risedronate gastrointestinal absorption is independent of site and rate of
      administration.
AB  - PURPOSE: Two studies were conducted to compare the absorption of risedronate
      administered as a solution to three different gastrointestinal sites (study A)
      and to determine the extent of absorption of risedronate solution administered by
      rapid and slow infusion to the second part of the duodenum (study B). METHODS:
      Each study was designed as a single-dose, crossover (three periods, study A; two
      periods, study B) trial in healthy male subjects, with a 14-day washout period
      between dosing. Subjects fasted overnight before drug administration and for 4
      hours after drug administration. In study A, a risedronate solution of 40 mg in
      30 mL of water was administered directly into the stomach, the second part of the
      duodenum, or the terminal ileum over 1 minute via a nasoenteral tube in a three
      period crossover design. In study B, a risedronate solution of 40 mg in 30 mL of
      water was administered directly into the second part of the duodenum over 1
      minute and over 1 hour in a randomized, two-period crossover design. Serum and
      urine samples were obtained for 48 hours after dosing for risedronate analysis.
      RESULTS: Eight subjects completed each study. No statistically significant site
      specific differences in any pharmacokinetic parameter were observed (study A).
      Based on the area under the serum concentration-time profile and the amount of
      drug excreted in the urine unchanged, the extent of risedronate absorption did
      not differ significantly following a rapid or a slow infusion (study B). Only
      minor symptomatic complaints were reported by subjects, such as headaches and
      body aches. CONCLUSIONS: These studies indicate that the rate and extent of
      risedronate absorption are independent of the site of administration along the
      gastrointestinal tract, and that the extent of absorption is not affected by the
      rate of administration.

PMID- 9523309
TI  - Drug marker absorption in relation to pellet size, gastric motility and viscous
      meals in humans.
AB  - PURPOSE: The objective of this study was to evaluate drug marker absorption in
      relation to the gastric emptying (GE) of 0.7 mm and 3.6 mm enteric coated pellets
      as a function of viscosity and the underlying gastric motility. METHODS: Twelve
      subjects were evaluated in a 3-way crossover study. 0.7 mm caffeine and 3.6 mm
      acetaminophen enteric coated pellets were concurrently administered with a
      viscous caloric meal at the levels of 4000, 6000 and 8000 cP. Gastric motility
      was simultaneously measured with antral manometry and compared to time events in
      the plasma profiles of the drug markers. RESULTS: Caffeine, from the 0.7 mm
      pellets, was observed significantly earlier in the plasma than acetaminophen,
      from the 3.6 mm pellets, at all levels of viscosity. Motility related size
      differentiated GE was consistently observed at all viscosity levels, however,
      less variability was observed with the 4000 cP meal. Specifically, the onset of
      absorption from the of 3.6 mm pellets correlated with the onset of Phase II
      fasted state contractions (r = 0.929, p < 0.01). CONCLUSIONS: The timeframe of
      drug marker absorption and the onset of motility events were not altered within
      the range of viscosities evaluated. Rather, the differences in drug marker
      profiles from the non-digestible solids were most likely the result of the
      interaction between viscosity and motility influencing antral flow dynamics. The
      administration of the two sizes of pellets and a viscous caloric meal with
      subsequent monitoring of drug marker profiles is useful as a reference to assess
      the influence of motility patterns on the absorption profile of orally
      administered agents.

PMID- 9523310
TI  - Comparison of the disposition of ester prodrugs of the antiviral agent 9-(2
      phosphonylmethoxyethyl)adenine [PMEA] in Caco-2 monolayers.
AB  - PURPOSE: To evaluate the potential of several bis-ester prodrugs of the antiviral
      agent 9-(2-phosphonylmethoxyethyl)adenine (PMEA, adefovir) to enhance the oral
      absorption of PMEA. METHODS: Caco-2 monolayers were used to estimate intestinal
      transport and metabolism of the bis(pivaloyloxymethyl)-ester [bis(POM)-] and a
      series of bis(S-acyl-2-thioethyl)-esters [bis(SATE)-] of PMEA. An LC-MS method
      was used for the identification of unknown metabolites which were formed from the
      SATE-esters. RESULTS: During transport across Caco-2 monolayers, all esters were
      extensively degraded as could be concluded from the appearance of the mono-ester
      and free PMEA in apical as well as basolateral compartments. Incubation of SATE
      esters with the monolayers resulted in the formation of two additional
      metabolites, which were identified as 2-thioethyl-PMEA and its dimerisation
      product. All ester prodrugs resulted in enhanced transepithelial transport of
      total PMEA (i.e. the bis-esters and their corresponding metabolites, including
      PMEA), but significant differences could be observed between the various esters.
      Transport of total PMEA ranged from 0.4 +/- 0.1% for the bis[S(methyl) ATE]-ester
      to 15.3 +/- 0.9% for the more lipophilic bis[S(phenyl)ATE]-PMEA. A relationship
      between total transport of the esters and their lipophilicity (as estimated by
      their octanol/water partition coefficient) was established (r2 = 0.87).
      Incubation of prodrug esters with homogenates from Caco-2 cells showed large
      differences in susceptibility of the compounds to esterases, the half-lives of
      the bis-esters varying from 4.3 +/- 0.3 min for the bis[S(phenyl)ATE]-PMEA to
      41.5 +/- 0.8 min for its methyl analogue. In addition, intracellularly formed
      PMEA was observed to be further converted by the cells to the diphosphorylated
      PMEA (PMEApp). CONCLUSIONS: Several SATE-esters of PMEA can be considered as
      potential alternatives to bis(POM)-PMEA, due to enhanced epithelial transport,
      sufficient chemical and enzymatic stability and adequate release of PMEA.
      Toxicological studies as well as in vivo experiments are required in order to
      further explore the potential of those SATE-esters as prodrugs for oral delivery
      of PMEA.

PMID- 9523311
TI  - Permeation of unfolded basic fibroblast growth factor (bFGF) across rabbit buccal
      mucosa--does unfolding of bFGF enhance transport?
AB  - PURPOSE: To investigate whether recombinant human basic fibroblast growth factor
      (rhbFGF) would permeate freshly-excised rabbit buccal mucosa. In addition, the
      effect of a permeation enhancer (Na+ glycocholate) and the possibility of
      reversibly unfolding the globular protein to a more linear conformation to
      increase the permeability of the test protein was evaluated. METHODS: The in
      vitro flux of bFGF through freshly-excised rabbit buccal mucosa was determined
      using side-by-side diffusion systems. Detection of bFGF was performed using
      gradient elution, reversed-phase high-pressure liquid chromatography (RP-HPLC).
      Fluorescence spectroscopy and heparin affinity chromatography were used to assess
      the tertiary structure of bFGF. RESULTS: Preliminary in vitro results have
      demonstrated that the bFGF flux increased from 1.4 +/- 0.13 ng min-1 cm-2 to 3.2
      +/- 0.38 ng min-1 cm-2 with the addition of 15 mM Na+ glycocholate (NaG) to the
      donor solution. Subsequent addition of guanidine HCl (GnHCl) to the donor
      solution (3 M) was not followed by a further increase in the flux of bFGF (2.9 +/
      0.26 ng min-1 cm-2). However, when the order of addition of the additives was
      reversed (GnHCl first followed by NaG), the flux of bFGF across rabbit buccal
      mucosa was increased. Upon addition of GnHCl, there was a significant (p < .05)
      increase in bFGF flux from 1.2 +/- 0.15 ng min-1 cm-2 to 5.0 +/- 0.58 ng min-1 cm
      2. Addition of NaG further increased the flux to 8.5 +/- 1.1 ng min-1 cm-2 which
      was approximately 3- to 3.5-fold greater than that determined with the protein
      alone in the absence of any donor phase additives. The percent of parent bFGF
      remaining following a 3-hr exposure of a bFGF solution to either the mucosal,
      serosal, or both sides of rabbit buccal mucosa were 54.3 +/- 5.7%, 71.8 +/- 6.3%,
      and 36.2 +/- 5.4%, respectively with the majority of parent bFGF lost during the
      first 15 minutes. A model endopeptidase (endoproteinase Arg-C from mouse
      submaxillary gland) was shown in vitro to contribute to the loss in parent bFGF.
      CONCLUSIONS: The permeation of bFGF across rabbit buccal mucosa may be
      significantly increased by initially unfolding the protein with GnHCl and then
      treating the tissue with the permeation enhancer, NaG. Refolding and possible
      reactivation of bFGF's bioactivity may occur following membrane transport and
      subsequent dilution into an infinite sink.

PMID- 9523312
TI  - Effects of non-covalent self-association on the subcutaneous absorption of a
      therapeutic peptide.
AB  - PURPOSE: To utilize an acylated peptide as a model system to investigate the
      relationships among solution peptide conformation, non-covalent self-association,
      subcutaneous absorption and bioavailability under pharmaceutically relevant
      solution formulation conditions. METHODS: CD spectroscopy, FTIR spectroscopy,
      equilibrium sedimentation, dynamic light scattering, and size exclusion
      chromatography were employed to characterize the effects of octanoylation on
      conformation and self-association of the 31 amino acid peptide derivative des
      amino-histidine(7) arginine(26) human glucagon-like peptide (7-37)-OH
      (IP(7)R(26)GLP-1). Hyperglycemic clamp studies were performed to compare the
      bioavailability, pharmacokinetics, and pharmacodynamics of solution formulations
      of oct-IP(7)R(26)GLP-1 administered subcutaneously to normal dogs. RESULTS:
      Octanoylation of IP(7)R(26)GLP-1 was shown to confer the propensity for a major
      solvent-induced conformational transition with an accompanying solvent- and
      temperature-dependent self-association behavior. Formulations were characterized
      that give rise to remarkably different pharmacodynamics and pharmacokinetics that
      correlate with distinct peptide conformational and self-association states. These
      states correspond to: (i) a minimally associated alpha-helical form (apparent
      molecular weight = 14 kDa), (ii) a highly associated, predominantly beta-sheet
      form (effective molecular diameter 20 nm), and (iii) an unusually large, micelle
      like soluble beta-sheet aggregate (effective molecular diameter 50 nm).
      CONCLUSIONS: Bioavailability and pharmacokinetics of a self-associating peptide
      can be influenced by aggregate size and the ease of disruption of the non
      covalent intermolecular interactions at the subcutaneous site. Hydrophobic
      aggregation mediated by seemingly innocuous solution formulation conditions can
      have a dramatic effect on the subcutaneous bioavailability and pharmacokinetics
      of a therapeutic peptide and in the extreme, can totally preclude its absorption.
      A size exclusion chromatographic method is identified that distinguishes
      subcutaneously bioavailable aggregated oct-IP(7)R(26)GLP-1 from non-bioavailable
      aggregated oct-IP(7)R(26)GLP-1.

PMID- 9523313
TI  - Synthesis and in vitro evaluation of chitosan-EDTA-protease-inhibitor conjugates
      which might be useful in oral delivery of peptides and proteins.
AB  - PURPOSE: To develop a novel mucoadhesive polymer that protects peptide drugs from
      degradation by secreted as well as membrane-bound proteases in the intestine, and
      to evaluate this polymer in vitro. METHODS: The serine protease inhibitors
      antipain, chymostatin and elastatinal were covalently linked to chitosan (poly-[1
      ->4]-beta-D-glucosamine). Thereafter, the complexing agent
      ethylenediaminetetraacetic acid (EDTA) was bound to the remaining primary amino
      groups of the polymer. The inhibitory effect of the resulting polymer-conjugate
      towards trypsin (EC 3.4.21.4), chymotrypsin (EC 3.4.21.1), elastase (3.4.21.36),
      carboxypeptidase A (EC 3.4.17.1), carboxypeptidase B (EC 3.4.17.2) and
      aminopeptidase N (EC 3.4.11.2) as well as its mucoadhesive properties were
      evaluated in vitro. RESULTS: Whereas the novel polymer-conjugate exhibited
      excellent swelling properties, its adhesive force was under our assay conditions
      42% lower than that of unmodified chitosan. However, the polymer-conjugate showed
      a strong inhibitory activity towards all tested serine proteases. Due to its
      additional high binding affinity towards bivalent metal ions, it also inhibited
      the Zn(2+)-dependent exopeptidases carboxypeptidase A, B and aminopeptidase N.
      CONCLUSIONS: The novel mucoadhesive polymer-conjugate described in this study
      seems to be a useful tool in overcoming the enzymatic barrier to perorally
      administered therapeutic peptides and proteins.

PMID- 9523314
TI  - Stealth PLA-PEG nanoparticles as protein carriers for nasal administration.
AB  - PURPOSE: The aim of the study was to encapsulate a model protein antigen, tetanus
      toxoid (TT), within hydrophobic (PLA) and surface hydrophilic (PLA-PEG)
      nanoparticles and to evaluate the potential of these colloidal carriers for the
      transport of proteins through the nasal mucosa. METHODS: TT-loaded nanoparticles,
      prepared by a modified water-in-oil-in-water solvent evaporation technique, were
      characterized in their size, zeta potential and hydrophobicity. Nanoparticles
      were also assayed in vitro for their ability to deliver active antigen for
      extended periods of time. Finally, 125I-TT-loaded nanoparticles were administered
      intranasally to rats and the amount of radioactivity recovered in the blood
      compartment, lymph nodes and other relevant tissues was monitored for up to 48 h.
      RESULTS: PLA and PLA-PEG nanoparticles had a similar particle size (137-156 nm)
      and negative surface charge, but differed in their surface hydrophobicity: PLA
      were more hydrophobic than PLA-PEG nanoparticles. PLA-PEG nanoparticles,
      especially those containing gelatine as an stabilizer, provided extended delivery
      of the active protein. The transport of the radiolabeled protein through the rat
      nasal mucosa was highly affected by the surface properties of the nanoparticles:
      PLA-PEG nanoparticles led to a much greater penetration of TT into the blood
      circulation and the lymph nodes than PLA nanoparticles. Furthermore, after
      administration of 125I-TT-loaded PLA-PEG nanoparticles, it was found that a high
      amount of radioactivity persisted in the blood compartment for at least 48 h.
      CONCLUSIONS: A novel nanoparticulate system has been developed with excellent
      characteristics for the transport of proteins through the nasal mucosa.

PMID- 9523315
TI  - Why rate of absorption inferences in single dose bioequivalence studies are often
      inappropriate.
AB  - PURPOSE: Peak drug concentration (Cmax) measures the extremity of drug exposure
      and is a secondary indicator of the extent of absorption after area under the
      concentration time curve (AUC). Cmax serves as the indicator of absorption rate
      in bioequivalence (BE) studies in the US (1). The use of Cmax, not the time to
      Cmax (Tmax), as the metric to assess absorption rate causes erratic inferences in
      BE studies, and incorrect conclusions for some. We can improve BE efficiency
      (i.e., get the answer right the first time), by properly analyzing the time to
      Cmax (Tmax) instead of Cmax. METHODS: We have previously redirected attention to
      Tmax as the unconfounded absorption rate variable, instead of Cmax, and have
      called for equally spaced sampling times during the suspected absorption phase to
      improve the performance of the rate metric (2). Equal spacing converts Tmax
      easily into a count variable and we illustrated an appropriate statistical
      analysis for counts. This paper provides some measurement theory concepts to help
      judge which is the more appropriate analysis, and also provides parametric
      confidence limits for Tmax treatment differences. Three separate BE studies are
      then analyzed by both methods. RESULTS: By focusing on the differences in
      conclusions, or inferences, this paper identifies three major issues with the
      current FDA "recommended" analysis of BE studies. First, Cmax, a continuous
      variable peak-height or extent measure has usurped Tmax's function and performs
      erratically as a substitute measure for the rate of absorption. Second, Tmax,
      should be analyzed as a discrete attribute, not as a continuous variable. Third,
      since several extent measures (AUC, Cmax), not one, are actually being analyzed,
      an adjustment for multiple testing is mandatory if we are to maintain the size of
      the test at the desired alpha level (13), and not inadvertently use a narrower
      bioequivalence window than is intended. These actions all can have serious
      unintended consequences on inferences, including making inappropriate ones.

PMID- 9523316
TI  - Analysis of chromameter results obtained from corticosteroid-induced skin
      blanching. I: Manipulation of data.
AB  - PURPOSE: One of the unresolved issues in the FDA Guidance document for topical
      corticosteroid bioequivalence testing is the method of manipulation suggested for
      the chromameter data. The purpose of this study was to manipulate the
      instrumental data from a typical blanching study in a number of ways to
      investigate the appropriateness of these procedures for comparison with the
      subjective visually-assessed results. METHODS: The human skin blanching assay
      methodology routinely practiced in our laboratories was utilised and the
      vasoconstriction produced by two corticosteroid formulations of different potency
      was assessed visually and instrumentally by use of a Minolta chromameter. The
      instrumental data were corrected for zero-time and unmedicated site readings. In
      addition, Euclidean distances were calculated using all data generated by the
      instrument. RESULTS: Individually the a-, b- and L-scale chromameter values are
      imprecise and there is negligible vasoconstriction response recorded for the
      moderately potent formulation. Arithmetical manipulation of the data as suggested
      by the FDA does not appear to improve the quality of the data in any way.
      Euclidean distance analysis more closely resembles the visual data and appears to
      have better precision. CONCLUSIONS: It is clear that mathematical correction of
      chromameter data is unnecessary, especially since the instrumental data are
      extremely imprecise. Furthermore, the assessment of each individual chromameter
      index does not adequately characterise the blanching response profile. It is
      therefore suggested that Euclidean distance may be a better measure on which to
      base an analysis of bioequivalence than the truncated data set methodology
      currently suggested by the FDA.

PMID- 9523317
TI  - Dihydroorotate dehydrogenase inhibitors: quantitative structure-activity
      relationship analysis.
AB  - PURPOSE: The main purpose of this study is to analyze the quantitative structure
      activity relationship of two series of dihydroorotate dehydrogenase inhibitors
      (leflunomide and quinoline carboxylic acid analogues), and to determine the
      structural requirements for optimum activity of these analogues. METHODS: A new
      CQSAR program was used in deriving regression equations and calculating the
      octanol/water partition coefficient and the molar refractivity values. The
      molecular modeling was performed using the HyperChem program. RESULTS:
      Statistically significant correlations were obtained using a combination of 3-4
      parameters. The structural requirements for optimum activity and critical regions
      for the inhibitory activity of dihydroorotate dehydrogenase were identified.
      CONCLUSIONS: The quantitative structure-activity relationship analysis
      demonstrated that two series of dihydroorotate dehydrogenase inhibitors may bind
      to different binding sites on the enzyme. These results provide a better
      understanding of dihydroorotate dehydrogenase inhibitor-enzyme interactions, and
      may be useful for further modification and improvement of inhibitors of this
      important enzyme.

PMID- 9523318
TI  - Biochemical characterization of a glucocorticoid-induced membrane protein (RM3/1)
      in human monocytes and its application as model system for ranking glucocorticoid
      potency.
AB  - PURPOSE: Upon glucocorticoid stimulation, human mononuclear leucocytes express an
      antigen, RM3/1, which characterizes a subpopulation of human monocytes and
      macrophages evolving in late phase of inflammation. We investigated biochemical
      properties of the RM3/1 antigen and correlations between antigen expression and
      glucocorticoid potency. METHODS: Biochemical properties were analyzed after
      solubilization by immunoaffinity methods and SDS-PAGE. RESULTS: Induction of the
      RM3/1 antigen is a glucocorticoid receptor mediated process, in contrast,
      inflammatory mediators such as LPS or TPA were not able to upregulate RM3/1
      expression. After SDS-PAGE, the antigen appeared as a 130 kDa (nonreduced)/150
      kDa (reduced) glycoprotein with a 25 kDa N-linked glycoportion. The
      interdependence between antigen density and glucocorticoid efficacy was assessed
      by calculation of relative antigen expression induced by dexamethasone,
      fluticasone propionate, budesonide, triamcinolone acetonide, flunisolide,
      beclomethasone, prednisolone and triamcinolone. Relative antigen expression was
      significantly correlated with the relative receptor affinity of the
      glucocorticoid. CONCLUSIONS: We described biochemical properties of the
      glucocorticoid-induced protein RM3/1. Though the precise role of the RM3/1
      antigen in the antiinflammatory process is not fully understood yet, an useful
      application of the induced expression could already be demonstrated for pre
      clinical screening of glucocorticoid potency.

PMID- 9523319
TI  - Pharmacological activity and membrane interactions of antiarrhythmics: 4D
      QSAR/QSPR analysis.
AB  - PURPOSE: This study was done to explore the relationships of both macroscopic and
      molecular level physicochemical properties to in-vivo antiarrhythmic activity and
      interactions with phospholipid membranes for a set of cationic-amphiphilic
      analogs. METHODS: The 4D-QSAR method, recently developed by Hopfinger and co
      workers (1), was employed to establish 3D-QSAR/QSPR models. Molecular dynamics
      simulations provided the set of conformational ensembles which were analyzed
      using partial least squares regression in combination with the Genetic Function
      Approximation algorithm to construct QSAR and QSPR models. RESULTS: Significant
      QSAR models for in-vivo antiarrhythmic activity were constructed in which logP
      (the partition coefficient), and specific grid cell occupancy (spatial)
      descriptors are the main activity correlates. LogP is the most significant QSAR
      descriptor. 4D-QSPR models were also developed for two analog-membrane
      interaction properties, the change in a membrane transition temperature and the
      ability of the analogs to displace adsorbed Ca(2+)-ions from phosphatidylserine
      monolayers. CONCLUSIONS: Spatial features, represented by grid cell occupancy
      descriptors, supplement partition coefficient, which is the most important
      determinant of in-vivo antiarrhythmic activity, to provide a comprehensive model
      for drug action. The QSPR models are less significant in statistical measures,
      and limited to interpretation of possible molecular mechanisms of action.

PMID- 9523320
TI  - Influence of surface properties at biodegradable microsphere surfaces: effects on
      plasma protein adsorption and phagocytosis.
AB  - OBJECTIVE: The objective of this work was to determine plasma protein adsorption
      and macrophage phagocytosis of biodegradable polyanhydride, polylactic acid and
      polylactic-co-glycolic acid microspheres prepared by both spray-drying and
      solvent evaporation techniques. METHODS: Microspheres were characterized by
      scanning electron microscopy (SEM), confocal laser microscopy, particle size
      distribution and zeta (zeta) potential determination. Plasma protein adsorption
      onto the microspheres was determined using a fluoroaldehyde reagent. Phagocytosis
      was evaluated by incubating microspheres containing the angiotensin II
      antagonist, L-158,809, with the macrophages in the presence or absence of the
      phagocytosis inhibitor cythochalasin D. The extent of phagocytosis was
      established by fluorescence determination of L-158,809 and by optical microscopy.
      The effect of amphiphilic poly(ethylene glycol) (PEG) derivatives on phagocytosis
      was determined using PEG-distearate incorporated into the microspheres. RESULTS:
      The average diameter of the microspheres, which depended on the polymer and the
      initial formulation, ranged from 0.9 to 3.2 micrometers. Zeta potential studies
      showed strong negative values irrespective of the polymer used for the spray
      dried formulations. The zeta potential was masked by the incorporation of PEG 400
      or PEG 1,400-distearate in the formulation. Confocal laser microscopy showed a
      homogenous dispersion of PEG (measured as PEG-fluorescein) in the microspheres.
      Protein adsorption was not observed for any of the microsphere formulations
      following incubation with bovine serum. Incubation of microspheres with murine
      macrophages showed that PEG-distearate inhibited phagocytosis at appropriate
      levels (0.1% w/w). Higher levels > 1% w/w of PEG-distearate) resulted in enhanced
      association with macrophages, despite the presence of the phagocytosis inhibitor
      cytochalasin D, indicating fusion between the microspheres and the plasma
      membrane. CONCLUSIONS: These results demonstrate that spray-dried PEG-containing
      microspheres can be manufactured and that an appropriate concentration of this
      excipient in microspheres results in decreased phagocytosis.

PMID- 9523321
TI  - Modification of the copolymers poloxamer 407 and poloxamine 908 can affect the
      physical and biological properties of surface modified nanospheres.
AB  - PURPOSE: To investigate the effects of the modification of the copolymers
      poloxamer 407 and poloxamine 908 on the physical and biological properties
      surface modified polystyrene nanospheres. METHODS: A method to modify poloxamer
      407 and poloxamine 908, introducing a terminal amine group to each PEO chain has
      been developed. The aminated copolymers can be subsequently radiolabelled with
      Iodinated (I125) Bolton-Hunter reagent. The aminated copolymers were used to
      surface modify polystyrene nanospheres. The physical and biological properties of
      the coated nanospheres were studied using particle size, zeta potential, in vitro
      non-parenchymal cell uptake and in vivo biodistribution experiments. RESULTS: The
      presence of protonated amine groups in the modified copolymers significantly
      affected the physical and biological properties of the resulting nanospheres,
      although the effects were copolyme specific. The protonated surface amine groups
      in both copolymers reduced the negative zeta potential of the nanospheres.
      Acetylation of the copolymer's free amine groups resulted in the production of
      nanospheres with comparable physical properties to control unmodified copolymer
      coated nanospheres. In vivo, the protonated amine groups in the copolymers
      increased the removal of the nanospheres by the liver and spleen, although these
      effects were more pronounced with the modified poloxamer 407 coated nanospheres.
      Acetylation of the amine groups improved the blood circulation time of the
      nanospheres providing modified poloxamine 908 coated nanospheres with comparable
      biological properties to control poloxamine 908 coated nanospheres. Similarly,
      modified poloxamer 407 coated nanospheres had only slightly reduced circulation
      times in comparison to control nanospheres. CONCLUSIONS: The experiments have
      demonstrated the importance of copolymer structure on the biological properties
      of surface modified nanospheres. Modified copolymers, which possess comparable
      properties to their unmodified forms, could be used in nanosphere systems where
      antibody fragments can be attached to the copolymers, thereby producing
      nanospheres which target to specific body sites.

PMID- 9523322
TI  - Efficacy and pharmacokinetics of site-specific cefazolin delivery using
      biodegradable implants in the prevention of post-operative wound infections.
AB  - PURPOSE: The study objective was to evaluate the efficacy and pharmacokinetics of
      cefazolin delivered locally as a glyceryl monostearate (GMS) based biocompatible
      implant for prevention of post-operative wound infection in Sprague Dawley rats
      subcutaneously inoculated with Staphylococcus aureus. METHODS: For the efficacy
      and pharmacokinetic studies, 18 rats were subcutaneously inoculated with 4.5 x
      10(7) CFU of S. aureus on the dorsum (6 per rat), and randomly assigned into
      three group of 6 rats each: (1) the control group, in which rats did not receive
      antibiotics, (2) the intermittent i.m. treatment group, in which rats received
      i.m. injections of 10 mg/kg cefazolin every 4 hr (total of 180 mg/kg in 3 days),
      and (3) the implant treatment group, in which rats were implanted subcutaneously
      with four Cefazolin-GMS implants in the vicinity of the inoculations. The
      implants were designed to deliver 180 mg/kg cefazolin over a 3 day period. For
      efficacy evaluation, the rats were euthanized one week post-inoculation and
      abscess count, weight and size were determined. RESULTS: Rats in the control
      group had developed 21 abscesses out of the 36 inoculations, indicating validity
      of the infection model. The local delivery of cefazolin resulted in complete
      eradication of the infection, since no abscesses formed in the rats in the
      implant group. In the IM treatment group, only one abscess was formed and no
      significant difference in efficacy between the two treatment groups was observed.
      The GMS implants sustained the release of cefazolin for a period of three days
      with only 3-fold fluctuations in plasma concentration (5.5-17.5 micrograms/ml).
      However, plasma concentrations after the intermittent IM administration of
      cefazolin fluctuated 110-fold between 44-0.4 micrograms/ml every 4 hr. The
      release rate of cefazolin from the implants was nearly zero order for the entire
      duration. Bioerosion of the implants was determined by examining the condition of
      the implants six weeks post-implantation. Two of the 12 implants had completely
      disappeared and the remaining implants were in a pasty form and had lost 20-80%
      of their weight. Absence of irritation or inflammation around the implants
      indicated biocompatibility of the GMS implants. CONCLUSIONS: Implantable system
      that provided a prolonged delivery of cefazolin was found to be effective against
      S. aureus infection, and demonstrated suitable pharmacokinetics and
      biocompatibility with significant bioerosion.

PMID- 9523323
TI  - DQAsomes: a novel potential drug and gene delivery system made from Dequalinium.
AB  - PURPOSE: Dequalinium, a drug known for over 30 years, is a dicationic amphiphile
      compound resembling bolaform electrolytes. The purpose of our work was to
      determine the state of aggregation of dequalinium in aqueous medium and to
      investigate both, its ability to bind DNA and its potential to serve as a novel
      non-viral transfection vector. METHODS: The form of aggregation was determined
      employing electron microscopic techniques. The DNA binding capacity of
      dequalinium was assayed using SYBR Green I stain. For in vitro cell transfection
      experiments plasmid DNA encoding for firefly luciferase was used. RESULTS:
      Dequalinium forms in aqueous medium liposome-like aggregates, which we term
      DQAsomes. These dequalinium vesicles bind DNA and they are able to transfect
      cells in vitro with an efficiency comparable to Lipofectin. CONCLUSIONS: Based on
      the intrinsic properties of dequalinium such as the in vivo selectivity for
      carcinoma cells and selective accumulation in mitochondria we propose DQAsomes as
      a novel and unique drug and gene delivery system.

PMID- 9523324
TI  - Development and utility of anti-PepT1 anti-peptide polyclonal antibodies.

PMID- 9523325
TI  - Reaction of acyl glucuronides with insulin in vitro: identification of an imine
      mechanism by electrospray ionization mass spectrometry.

PMID- 9523326
TI  - Use of the stable isotopes technique to evaluate the bioavailability of a
      pharmaceutical form of magnesium in man.

PMID- 9523327
TI  - A cross-section device to improve visualization of fluorescent probe penetration
      into the skin by confocal laser scanning microscopy.

PMID- 9523329
TI  - Electron microscopy and spectroscopical studies on the coloured patches on the
      wing of a butterfly, Graphium sarpedon (Lepidoptera: Papillionidae) with
      reference to their photobiological and electrical properties.
AB  - The surface ultra-structural features of the coloured patches on the wing of a
      butterfly Graphium sarpedon have been studied with the help of scanning electron
      microscopy. Comparisons have been made between the dark brown area and the light
      green patches of the wing. A diffraction grating pattern with 15 lines per micron
      2 with a uniform spacing of about 1 micron is present in the light green patches.
      A slightly coarser grating is present on the dark brown area, which constitutes
      the major portion of the wing. Sensilla chaetica was found on both the light
      green and dark brown area. A special type of sensilla trichodea with a big socket
      and some elongated projections were localized only on the light green patches.
      This region of the wing also contains some spherical structures with a diameter
      of 0.5 to 0.6 micron. The infra-red spectroscopy has revealed some differences in
      the nature and position of the peaks in the low-energy region in the dark brown
      area and the light green patches. The atomic absorption spectroscopy also shows
      qualitative as well as quantitative differences in the inorganic set up of the
      two regions. The electron spin resonance spectroscopy reveals the presence of a
      peak in the dark brown region only, indicating the presence of free radical in
      it. The differences observed in the ultra-structural and spectroscopical
      features, and also in the inorganic components of the two regions, are discussed
      in relation to their physical and physiological properties.

PMID- 9523328
TI  - A large-scale process to produce microencapsulated proteins.

PMID- 9523330
TI  - Arbutin increases the pigmentation of cultured human melanocytes through
      mechanisms other than the induction of tyrosinase activity.
AB  - We assessed the effects of arbutin on the pigmentation of cultured normal human
      melanocytes. As indicated by a cell-blotting assay, arbutin at concentrations in
      the range of 0.5-8 mM increased the pigmentation of the cultured melanocytes,
      while kojic acid at concentrations in the range of 0.5-4 mM decreased the
      pigmentation. The pigmentation-augmenting effect of arbutin was further confirmed
      by the results of a cell-pelleting assay, the traditional method of assessment.
      Treatment of the cells with arbutin increased the melanin content of the cells
      and the protein content as well. On the other hand, the tyrosinase activity in
      the cells was reduced by arbutin treatment. The levels of transcription of
      tyrosinase and tyrosinase related protein-1 genes were not affected by arbutin
      treatment as indicated by a semi-quantitative reverse transcription-polymerase
      chain reaction assay. These results demonstrate that arbutin promotes an increase
      in pigmentation of cultured human melanocytes that is not mediated by augmented
      tyrosinase activity.

PMID- 9523331
TI  - In situ and in vitro expression of protein kinase C alpha in human melanocytes.
AB  - Protein kinase C (PKC) is a multigene family of at least 12 isoforms involved in
      the transduction of extracellular signals. We investigated whether PKC-alpha, a
      major isoform known to be relatively abundant in brain tissue, is increased in
      human melanocytes relative to keratinocytes in vitro and in situ.
      Immunohistochemical staining for PKC-alpha in frozen neonatal human foreskin
      exhibited intermittent 2-3 + staining along the basal cell layer consistent with
      melanocytes, and 0-1 + staining of keratinocytes (on a scale of 0-3). Microscopic
      densitometry of the intermittent cellular staining was at least 3-fold greater
      than that of adjacent keratinocyte cell cytoplasm. Sequential frozen sections
      revealed similar intermittent cell staining with PKC-alpha and Mel-5 (tyrosinase
      related protein-1), known to specifically react with melanocytes. Northern blot
      analysis with a specific cDNA probe for PKC-alpha showed strong PKC-alpha mRNA
      expression in cultured melanocytes, whereas PKC-alpha mRNA in cultured non
      stratifying keratinocytes was expressed at low levels. Western blot analysis
      revealed a prominent PKC-alpha band at approximately 80 kDa in melanocytes as
      opposed to a weak band in keratinocytes. Densitometry of the northern and western
      blots revealed that melanocytes had at least 10-fold more PKC-alpha mRNA and
      approximately 6-fold more PKC-alpha protein expression than keratinocytes. Total
      PKC activity measured in vitro revealed that melanocytes had 5-fold more activity
      than keratinocytes. The marked difference in melanocyte and keratinocyte
      expression of PKC-alpha provides further evidence for cell type specificity in
      the balance of PKC-alpha expression and may implicate differential PKC isoform
      signaling pathways in neuro-ectodermally derived cells.

PMID- 9523332
TI  - N-acetyl-L-tyrosine (NAT) as a substrate for mushroom tyrosinase.
AB  - N-acetyl tyrosine (NAT) is hydroxylated by mushroom tyrosinase and the N-acetyl
      dopa formed is oxidized by the enzyme to N-acetyl dopaquinone (lambda max = 390
      +/- 10 nm). H2O2 and NH2OH each shortened the lag period of NAT hydroxylation by
      the enzyme. H2O2 had an effect on the changes with time in the spectrum of
      product(s) formed and on the spectrum of the final product(s) obtained when NAT
      was hydroxylated by mushroom tyrosinase, in a manner suggesting that H2O2
      converts N-acetyl dopaquinone to a pink-violet product(s) (lambda max = 490 nm),
      whereas such a product(s) was not formed in the absence of H2O2. A pink-violet
      product(s) (lambda max 490 +/- 20 nm) was also formed when NAT was hydroxylated
      by mushroom tyrosinase in the presence of NH2OH or para amino benzoic acid
      (PABA), probably as a result of an interaction between N-acetyl dopaquinone and
      NH2OH or PABA forming mono- or di-oximes. Kojic acid (5-hydroxy-2-hydroxymethyl)
      4H-pyran-4-one) inhibited effectively the rate of NAT hydroxylation by mushroom
      tyrosinase in the absence or presence of H2O2. When NAT was oxidized by the
      enzyme in the absence of kojic acid, N-acetyl dopaquinone was formed at once and
      a shoulder at 490-530 nm appeared later. Under identical conditions but in the
      presence of kojic acid, a yellow product(s), characterized by a peak at 320 +/-
      10 nm, was detected, suggesting that N-acetyl dopaquinone oxidizes kojic acid to
      the yellow product(s). Maltol (3-hydroxy-2-methyl-4H-pyran-4-one), a gamma-pyrone
      derivative structurally related to kojic acid, also inhibited the rate of NAT
      hydroxylation by mushroom tyrosinase. The addition of maltol at the plateau phase
      of the reaction resulted in an immediate decline in absorbance at 400 nm,
      suggesting that maltol conjugates with N-acetyl dopaquinone, yielding a
      product(s) characterized by a lower extinction coefficient at 400 nm than that of
      N-acetyl dopaquinone alone. The final brown-red product(s) formed when NAT was
      hydroxylated by mushroom tyrosinase was bleached in the presence of ascorbic acid
      or H2O2.

PMID- 9523333
TI  - The mechanism of melanocyte dendrite formation: the impact of differentiating
      keratinocytes.
AB  - In human epidermis one dendritic melanocyte interacts with about 36 keratinocytes
      and supplies them with melanin. In contrast to the vivo situation melanocytes in
      culture are far less dendritic. In the present study different culture systems
      were tested in order to observe the mechanism of melanocyte dendrite formation.
      In particular, we focused on the role of keratinocytes in this process. Time
      lapse studies revealed that only differentiated keratinocytes enhance melanocyte
      dendricity. Differentiated keratinocytes form connected cell sheets, which attach
      to part of the melanocyte plasma membrane. By contraction and retraction of
      keratinocyte units, new dendrites were drawn out from the melanocytes.
      Melanocytes remain passive during this process, which is indicated by the
      observation that sometimes extended dendrites could not withstand the tension and
      shear.

PMID- 9523334
TI  - Cellular plasticity among axolotl neural crest-derived pigment cell lineages.
AB  - Many of the factors and mechanisms guiding the migration/differentiation of
      neural crest cells that give rise to a number of distinguishable cell types,
      including all dermal and epidermal pigment cells, remain unknown. The axolotl
      possesses three pigment cell types that differentiate according to specific
      developmentally programmed sequences and contribute to pigment pattern in the
      adult. A single lineage of the crest that becomes restricted to one of three
      pigment cell types gives us the opportunity to examine the existence of a neural
      crest stem cell population and the potential for trans-differentiation events.
      Interpretations of experiments involving drug-treated and mutant axolotls
      implicate cellular plasticity leading to observed phenotypes. We present results
      from recent in vitro studies designed to identify parameters influencing
      differentiation events of individual neural crest-derived pigment cell lineages.
      We demonstrate that the differentiation of xanthophores is enhanced, while that
      of the melanophores are inhibited in guanosine-supplemented neural crest cell
      cultures. Data suggest that the increase in one pigment cell population is at the
      expense of another, indicative of cellular plasticity. Videomicroscopy used in
      this study agrees with an abundance of correlative evidence supporting the
      hypothesis of transdifferentiation events among neural crest-derived pigment cell
      populations. The embryonic neural crest-derived pigment cell system is an ideal
      model to study differentiation of multipotential stem cells that play critical
      roles in patterning.

PMID- 9523336
TI  - Fallacies of numerology.

PMID- 9523335
TI  - alpha-MSH and melanogenesis in normal human adult melanocytes.
AB  - Normal human skin melanocytes do not pigment consistently to alpha-melanocyte
      stimulating hormone (alpha-MSH) in culture. The aim of this study was to
      establish media conditions in which to obtain a reproducible melanogenic response
      to alpha-MSH in these cells. Twenty-five media of varying mitogen composition
      were examined. As previously noted by other workers, melanocyte morphology and
      proliferation are greatly affected by media composition. However, under the
      majority of media conditions that supported melanocyte survival and
      proliferation, cells did not respond to alpha-MSH with any consistent increase in
      dopa oxidase activity or melanin content. In only one medium condition, where
      basic fibroblast growth factor (bFGF) was the sole mitogen present, alpha-MSH
      induced both an increase in dopa oxidase activity (at 48%) and in melanin content
      (of 283%).

PMID- 9523337
TI  - Adult leukaemia: what is the role of currently known risk factors?
AB  - Leukaemias are a heterogeneous group of tumours including acute and chronic
      forms. Considerable efforts have been made to identify risk factors for these
      diseases, but only a minority of leukaemia cases can currently be attributed to
      identified or hypothesized factors. This review highlights recent epidemiological
      literature concerning adult leukaemia, discussing in detail the hereditary,
      environmental and medical risks. Chromosomal syndromes and genetically based
      diseases carry a high risk of leukaemia, but rarely occur in the population.
      Environmental and occupational exposures to chemicals including pesticides have
      been widely studied, although the results are not consistent, with the exception
      of benzene. Smoking seems to be a weak causal risk factor. The risk of ionizing
      radiation has further been quantified in recent studies, although the effects of
      low doses have not yet been clarified. The results for non-ionizing radiation
      continue to be inconsistent, but a large effect of electromagnetic fields on the
      risk of leukaemia appears to be unlikely. Medically applied radio- and
      chemotherapy are clearly associated with subsequent leukaemia development, and
      there are links between leukaemia and viral infections. Future research should
      emphasize the shortcomings in exposure assessment that pervade many studies, and
      interactions between different risk factors need to be taken into consideration.

PMID- 9523338
TI  - Monte Carlo simulation of diffusion and reaction in water radiolysis--a study of
      reactant 'jump through' and jump distances.
AB  - In Monte Carlo simulations of water radiolysis, the diffusion of reactants can be
      approximated by "jumping" all species randomly, to represent the passage of a
      short period of time, and then checking their separations. If, at the end of a
      jump, two reactant species are within a distance equal to the reaction radius for
      the pair, they are allowed to react in the model. In principle, the possibility
      exists that two reactants could "jump through" one another and end up with a
      separation larger than the reaction radius with no reaction being scored.
      Ignoring this possibility would thus reduce the rate of reaction below that
      intended by such a model. By making the jump times and jump distances shorter,
      any error introduced by 'jump through' is made smaller. This paper reports
      numerical results of a systematic study of 'jump through' in Monte Carlo
      simulations of water radiolysis. With a nominal jump time of 3 ps, it is found
      that more than 40% of the reactions of the hydrated electron with itself and of
      the H atom with itself occur when reactions during 'jump through' are allowed.
      For all other reactions, for which the effect is smaller, the contributions of
      'jump through' lie in the range 1%-16% of the total. Corrections to computed rate
      constants for two reactions are evaluated for jump times between 0.1 and 30 ps.
      It is concluded that jump-through corrections are desirable in such models for
      jump times that exceed about 1 ps or even less. In a separate study, we find that
      giving all species of a given type the same size jump in a random direction
      yields results that are indistinguishable from those when the jump sizes are
      selected from a Gaussian distribution. In this comparison, the constant jump size
      is taken to be the root-mean-square jump size from the Gaussian distribution.

PMID- 9523339
TI  - Monte Carlo simulation of DNA strand-break induction in supercoiled plasmid
      pBR322 DNA from indirect effects.
AB  - We present a new Monte Carlo simulation code system (DBREAK) of the detailed
      events that occur when ionizing radiation interacts with water and DNA molecules.
      The model treats the initial energy deposition by radiation, the formation of
      chemically active species, subsequent diffusion-controlled chemical reactions,
      and induction of DNA strand breaks. DBREAK assumes one-hit single-strand break
      (SSB) and two-hit double-strand break (DSB) mechanisms. A high-resolution model
      of plasmid DNA structure has been introduced. The calculated results are compared
      with the results of previously performed experiments of the same type. Under
      aerobic conditions, 89.4% of the DNA damage was attributed to OH-radical and
      10.5% and 0.1% to eaq- and H, respectively. We also compared the differences
      between liquid-water track structure and gas-phase-water track structure. The
      calculated yield of SSBs by liquid-water track structure exceeded that of gas
      phase-water track structure by a factor of 1.2.

PMID- 9523340
TI  - A metabolic approach to simulating the dynamics of C-14, H-3 and S-35 in sheep
      tissues.
AB  - The results of a study in which groups of sheep were given single oral
      administrations of 14C, 3H and 35S and then slaughtered over a period of 1 year
      are reported. The experimental data were used to investigate the potential of
      metabolically based models for describing the transfer of the three radionuclides
      to sheep tissues. The structure of these models is based upon a simplified
      understanding of the transfer of the macro-elements C, H and S by processes such
      as respiration and protein synthesis/degradation. A consequence of this approach
      is that the three models have many common parameters. The models reproduced the
      general trends of the observations, accounting for 74%, 66%, and 58% of the
      observed variation in the 14C, 3H and 35S data, respectively, suggesting that
      they may provide a useful alternative approach to modelling the transfer of these
      radionuclides. The models presented are limited to the particular experimental
      situation for which they were developed, and further experimental work would be
      required to extend them. However, such metabolically based models have great
      potential: for example, they should be able to account for the influence of
      dietary intake, physiological status or the form of the radionuclide in the
      animals diet (e.g. tritiated water or organically bound tritium).

PMID- 9523341
TI  - Analysis of chromosome aberrations in human peripheral lymphocytes induced by 5.4
      keV x-rays.
AB  - Irradiation of human lymphocytes by x-rays has been seen, in past studies, to
      produce increasing frequencies of chromosome aberrations at lower x-ray energies.
      However, in one earlier irradiation experiment with chromium x-rays, the relative
      biological effectiveness (RBE) did not appear to be larger than that of hard x
      rays, especially at higher doses. A possible reason for this unexpected result
      may have been the irradiation and culture conditions. We have, therefore, in the
      present study used a technique that has been developed in our laboratory to
      ensure uniformity of irradiation within lymphocytes and to avoid artefacts due to
      the cell cycle kinetics. Monolayers of 3-h-stimulated lymphocytes were exposed to
      5.4 keV x-rays. A linear-quadratic dose-response was found for dicentrics. The
      comparison to an earlier finding with 220 kV x-rays shows the expected result of
      the RBE of the 5.4 keV x-rays to be above that of 220 kV x-rays. The
      intercellular distribution of dicentrics did not differ significantly from a
      Poisson distribution.

PMID- 9523342
TI  - Radiation-induced genetic instability: no association with changes in
      radiosensitivity or cell cycle checkpoints in C3H 10T1/2 mouse fibroblasts.
AB  - We investigated various phenotypic characteristics of radiation-induced
      morphologically transformed C3H 10T1/2 mouse fibroblasts. The cells were treated
      with 8 Gy x-rays, and type II/III foci were isolated. Cell lines were developed
      from these foci, and subsequently clones were established from these focal lines.
      The clones were examined for DNA content, radiosensitivity and inducible cell
      cycle arrests. Besides the morphological changes associated with the transformed
      state, the major difference between the isolated focal lines or derived clones
      and the parental C3H 10T1/2 line was one of ploidy. The transformed cells often
      displayed aneuploid and multiple polyploid populations. No change in the
      radiosensitivity of the transformed cells was observed. Furthermore, the two
      major radiation- and staurosporine-induced G1 and G2 cell cycle arrests observed
      in the parental cell line were also observed in the morphological transformants,
      suggesting that checkpoint function was normal.

PMID- 9523343
TI  - Thyroid dose and thyroid cancer incidence after the Chernobyl accident:
      assessments for the Zhytomyr region (Ukraine).
AB  - In the Zhytomyr region, about 52,000 measurements of the 131I activity in
      thyroids were performed. On the basis of these measurements, individual doses
      have been assessed for the people monitored and age-dependent average doses have
      been estimated for those settlements with more than 11 direct measurements. In
      order to estimate the pattern of thyroid exposure in the Zhytomyr region, these
      doses have been interpolated or extrapolated to population groups who were not
      monitored during May-June 1986. For this purpose, a model has been developed
      based on a correlation between thyroid dose estimates with the 137Cs deposition
      and the co-ordinates of the settlements relative to Chernobyl. Collective doses
      of people who were born in the years 1968 to 1986 were calculated. The radiation
      induced thyroid cancer incidence in the period 1991 to 1995 was assessed by
      subtracting the spontaneous incidence from the observed incidence. The result is
      considerably lower than that observed in longer periods after external exposures.
      Possible reasons for this difference are discussed.

PMID- 9523344
TI  - Measurement of resuspended aerosol in the Chernobyl area. Part II. Size
      distribution of radioactive particles.
AB  - Size distribution measurements of particulate radionuclides were performed at two
      sites in the Chernobyl 30-km exclusion zone using several cascade impactors. The
      results obtained in the period September 1986 till June 1993 were discussed with
      regard to the general assumption of a log-normal activity size distribution in
      inhalation dose assessment. At Zapolie (a site 14 km from the Chernobyl reactor)
      a bimodal distribution was observed in 91% of all measured distributions. In most
      cases the medians were about 4 microns and in the range 20-30 microns. According
      to soil granulometric data this finding was explained by superimposing two
      processes: local resuspension and advective transport of radioactive aerosol from
      highly contaminated territories. The mean air concentration showed an increasing
      proportion of inhalable particles over the years since the accident. In 1993 the
      inhalable fraction was about 48% of the total concentration. At Pripyat, a site
      situated within a highly contaminated area, unimodal types of size distributions
      were predominant with the median diameters in the range 5-10 microns for 137Cs.
      For the three nuclides 137Cs, 144Ce and 106Ru, very similar types of distribution
      were observed. Apparently, the radioactive aerosol was of fuel origin. During a
      forest fire at a distance of 17 km, the majority of the radioactivity was
      associated with submicrometer particles with median diameters in the range 0.28
      0.50 micron.

PMID- 9523345
TI  - PARATI--a dynamic model for radiological assessments in urban areas. Part III:
      Parameter uncertainty analysis.
AB  - The uncertainties in the exposure predictions after contamination of an urban
      area due to the variabilities in environmental transfer parameters and in dose
      conversion factors have been estimated. This was done using the "Latin Hypercube"
      sampling scheme and the computer codes PRISM and PARATI. For the scenario 'urban
      contamination by 137Cs' and the population groups considered, the main sources
      contributing to the uncertainty in the resulting exposures are the limited
      knowledge of the initial deposition and retention, the weathering processes, the
      actual urban environments, and the characteristics and habits of the population.
      The effect of the parameter uncertainties on the variability of the dose is
      almost constant over time.

PMID- 9523346
TI  - Experimentally determined translocation of 134Cs in potatoes. Comparison with the
      radioecological model ECOSYS-87 and literature data.
AB  - The results of a greenhouse experiment on the translocation rate of 134Cs from
      potato leaves to tubers were compared with calculations of the radioecological
      model ECOSYS-87 and other literature values. The 134Cs activities applied at
      three development stages (three pinnate leaves fully developed, onset of
      flowering, onset of yellowing) to leaves of the plant were taken as starting
      points for the model to calculate the activity in the tubers at harvest. The
      default yield in the model was replaced by the experimentally obtained values.
      The translocation rate measured in the greenhouse experiment was 4 to 14 times
      higher than the calculations of the model. Some possible reasons for such a high
      translocation rate, compared with the literature data, are discussed. Based on
      these comparisons, it is concluded that maximal translocation occurs at the
      growth stage of flowering of a crop and that the development stage of a crop
      might be a stronger parameter to describe the time dependency of translocation
      than the usually applied parameter 'days before harvest'.

PMID- 9523347
TI  - A response to "Perinatal mortality in Bavaria, Germany, after the Chernobyl
      accident" by Grosche et al.

PMID- 9523348
TI  - Response to the letter to the editor by H. H. Rossi.

PMID- 9523349
TI  - Response to the letter to the editor by J. D. Boice and L.-E. Holm.

PMID- 9523350
TI  - Mutation in the exon 10 (R173W) of the hydroxymethylbilane synthase gene in two
      unrelated Japanese families with acute intermittent porphyria.
AB  - Acute intermittent porphyria (AIP) is an inherited disorder characterized by a
      deficiency of hydroxymethylbilane synthase (EC 4.3.1.8.; HMBS), the third enzyme
      in the heme biosynthetic pathway. To date, 113 different HMBS gene mutations have
      been reported in the world. However, there were a few reports of the gene
      mutations in the Japanese AIP patients. We studied the gene mutation in two
      unrelated AIP families in the San-in district, a local area of Western Japan. The
      overlapping 6 fragments of the HMBS gene, amplified by the reverse transcript
      polymerase chain reaction, were analyzed by the single-strand conformation
      polymorphism with silver staining technique. The abnormal fragment from a member
      of one family was sequenced to detect the C to T substitution at 517 nucleic acid
      position of cDNA, which led to a missense mutation of arginine to tryptophan
      exchange at an amino acid level (R173W). This mutation located in exon 10 created
      a new site of the MSP 1 restriction endonuclease and was screened by the
      amplified fragment of exon 10 from genomic DNA with the MSP 1 digestion. The
      mutation was detected totally in three members of the family and interestingly
      also in two patients of an unrelated family. This mutation has been reported
      widely in the world independently, such as in a Swedish, a Canadian, a Finnish,
      and a French family, but is the first in Japanese patients. The screening method
      for this mutation is useful for diagnosis in Japanese AIP patients.

PMID- 9523351
TI  - Nucleotide and amino acid sequences of the monkey P450 2B gene subfamily.
AB  - The nucleotide sequence of a cDNA coding for monkey cytochrome P450 (P450) 2B has
      been determined. Using antibody against P450 CMLa which had been purified from
      hepatic microsomes of untreated cynomolgus monkeys, a cDNA clone with 2,275 bp
      insert (Mac2B) was isolated from a gamma gt11 cDNA library prepared from hepatic
      mRNA from an untreated rhesus monkey. The cloned insert was sequenced and found
      to contain an open reading frame coding for a polypeptide of 491 amino acids. The
      molecular weight calculated from the deduced amino acid sequence was 55,969. The
      N-terminal 34 amino acids encoded by Mac2B were identical to those determined by
      Edman degradation analysis of purified cynomolgus monkey P450 CMLa. The
      nucleotide and the deduced amino acid sequences of Mac2B which is now called
      CYP2B17 were the most similar to those of human P450 2B6 among the P450 2B
      subfamily and those sequences of Mac2B were 94% and 90% identical to those of
      human P450 2B6, respectively.

PMID- 9523352
TI  - cis-Diamminedichloroplatinum induces peroxisomes as well as CYP4A1 in rat kidney.
AB  - Effects of cis-diamminedichloroplatinum (cisplatin) on rat kidney were
      investigated. Clinical parameters in rat urine and blood were studied. Blood urea
      nitrogen (BUN) and creatinine in blood and K+ in urine increased, but Na+ in
      urine decreased. Contents of total P450 and metabolic activities towards lauric
      acid and arachidonic acid in rat renal microsomes were not changed by cisplatin
      treatment. The levels of P450 isozymes (CYP4A1, 4A2, 4A8 and 2C23) were
      determined in rat renal microsomes by immunoblotting. The levels of CYP4A2 and
      4A8 which are lauric acid omega-hydroxylases were not changed, but the levels of
      CYP2C23 and 4A1 were increased significantly by cisplatin treatment. Effects of
      clofibrate, a typical inducer for CYP4A1, on rat kidney were compared with those
      of cisplatin. Clofibrate induced palmitoyl CoA oxidase (a marker enzyme of
      peroxysome), CYP4A1, and CYP4A2 and reduced triglyceride level in plasma.
      Cisplatin had similar effects to clofibrate and induced peroxysomes as well as
      CYP4A1, although the effects were at a lesser extent than those of clofibrate.
      The induction levels of CYP4A1 correlated with increased levels of BUN. The
      present findings suggest that induction of P450 by cisplatin may take part in the
      renal injury or nephrotoxicity of cisplatin.

PMID- 9523353
TI  - Expression of Shaker-type voltage-gated potassium channel genes in the guinea
      pig.
AB  - Few potassium channel genes have been isolated in the guinea-pig despite detailed
      electrophysiological characterization of potassium channels in the guinea-pig
      heart. We obtained partial clones of Shaker-type potassium channel genes in the
      guinea-pig and demonstrated their tissue distribution. Partial clones of the
      Shaker-type potassium channel genes were obtained by RT-PCR or genomic PCR. mRNA
      expression was measured by RNase protection assays in the heart, brain, and
      skeletal muscle. Three of the five obtained channel genes were expressed in the
      guinea-pig heart; Kv1.2, Kv1.3, and Kv1.6. Kv 1.6 expression was markedly at a
      higher level in the atrium than in the ventricle. Expression of the channel genes
      in the guinea-pig was different from that in human and rat, which may contribute
      to the species-specific action potential waveform.

PMID- 9523354
TI  - Clinical significance of serum P53 antibody in patients with gastric cancer.
AB  - The presence of serum p53 antibody has been reported to have prognostic
      significance in patients with breast and ovarian cancers. In order to clarify
      clinical and prognostic significance of p53 antibody in serum, we measured p53
      antibody in patients with gastric cancer. Twenty-five patients with gastric
      cancer were examined as well as 9 patients with gastric polyp as controls. Eight
      of 25 patients (32%) with gastric cancer were positive for p53 antibody, while no
      patients with gastric polyp were positive in gastric polyp group (p < 0.05). The
      presence of p53 antibody was significantly associated with histology, liver
      metastasis and stage classification in gastric cancer (p < 0.05, respectively).
      Presence of liver metastasis, type of histology and presence of p53 antibody are
      independent prognostic factors (p < 0.05, respectively). The overall survival in
      patients with p53 antibody was significantly shorter survival than for those
      without antibody (p < 0.05%). These data suggest that p53 antibody serves as one
      of the prognostic factors in gastric cancer.

PMID- 9523355
TI  - Effect of monocrotaline metabolites on glutathione levels in human and bovine
      pulmonary artery endothelial cells.
AB  - After being dehydrogenated by cytochrome P450 enzymes in the liver,
      monocrotaline's highly-reactive pyrrole metabolite, dehydromonocrotaline, is
      believed to interact with pulmonary artery endothelial cells to initiate a
      pulmonary vascular toxicity resembling pulmonary hypertension. Glutathione, an
      abundant antioxidant in pulmonary artery endothelial cells, has been shown to
      react with and detoxify the pyrrolic metabolites derived from monocrotaline in
      the liver. Using high-performance liquid chromatography with electrochemical
      detection, glutathione levels were measured in a time- and dose-dependent manner
      in human pulmonary artery endothelial cells following treatment with
      dehydromonocrotaline, dehydroretronecine and N-ethylmaleimide and bovine
      pulmonary artery endothelial cells after treatment with dehydromonocrotaline. The
      bovine cells had 40% less glutathione than the human in the control groups.
      Bovine pulmonary artery endothelial glutathione levels were depleted 20% more
      than the human at 15 minutes when treated with 100 microM dehydromonocrotaline.
      15 microM N-ethylmaleimide caused an 80% depletion of glutathione compared to a
      30% depletion with 15 microM dehydromonocrotaline in human pulmonary artery
      endothelial cells.

PMID- 9523356
TI  - Dietary iron concentration alters LDL oxidatively. The effect of antioxidants.
AB  - Low-density lipoprotein (LDL) cholesterol participates in the atherosclerotic
      process only after oxidative modification (o-LDL). Persons with elevated body
      iron concentrations are at higher risk of atherosclerosis. Iron in vitro is
      capable of oxidizing LDL, but it is unknown whether or not high dietary iron
      concentrations alter LDL in vivo. The aim of this study was, therefore, to
      investigate (i) whether dietary iron concentrations cause LDL-cholesterol
      oxidation and (ii) whether antioxidants can prevent such changes. Rats received
      diets differing only in iron concentration: 35 mg/kg, 150 mg/kg or 300 mg/kg
      diet. A LDL-VLDL particle was isolated and the following parameters measured:
      malondialdehyde and lipid hydroperoxide concentrations (as an indication for
      lipid peroxidation); alpha-tocopherol and retinol concentrations (as
      antioxidants); protein sulfhydryl and carbonyl concentrations (as an indication
      of protein modification); agarose gel electrophoresis and cholesterol/protein
      ratio. Dietary iron increased LDL-VLDL lipid peroxidation (malondialdehyde and
      lipid hydroperoxide concentrations), protein modification (sulfhydryl
      concentration), agarose migration distance and band width as well as
      cholesterol/protein ratio. Increased quantities of dietary iron led to a higher
      degree of oxidative change in LDL-VLDL. Lipid peroxidation, as well as protein
      modification, occurred, suggesting apoB changes. This was probably due to
      diminished antioxidant concentrations of alpha-tocopherol and beta-carotene.
      Antioxidant supplementation (alpha-tocopherol and beta-carotene), however,
      prevented all the above changes and could be helpful in the prevention of
      atherosclerosis.

PMID- 9523357
TI  - Insulinotropic action of the polyacetate esters of metabolized and non
      metabolized monosaccharides in pancreatic islets from normal and diabetic rats.
AB  - The polyacetate esters of selected monosaccharides were recently found to either
      stimulate insulin release or inhibit glucose-stimulated insulin secretion in
      islets from normal rats. The present study extends such findings both to new
      combinations of either D-glucose or L-leucine and some polyacetate esters and to
      hereditarily diabetic, as distinct from normal, rats. In the normal animals, 2
      deoxy-D-glucose tetraacetate (1.7 mM) increased both glucose- and leucine
      stimulated insulin output. The secretory response to L-leucine was also increased
      by beta-D-glucose pentaacetate, but inhibited by alpha-D-galactose pentaacetate
      and D-mannoheptulose hexaacetate (1.7 mM) in the islets of normal rats. In the
      diabetic rats, the secretory response to D-glucose (8.3 mM) was increased by
      alpha- or beta-D-glucose pentaacetate and 2-deoxy-D-glucose tetraacetate (1.7
      mM), inhibited by alpha-D-galactose pentaacetate and D-mannoheptulose
      hexaacetate, and unaffected by beta-L-glucose pentaacetate, all esters being
      tested at 1.7 mM concentration. L-Leucine-stimulated insulin release was also
      increased by alpha-D-glucose pentaacetate, but not significantly affected by beta
      D-galactose pentaacetate, beta-L-glucose pentaacetate, 2-deoxy-D-glucose
      tetraacetate and D-mannoheptulose hexaacetate in the islets of diabetic animals.
      These findings suggest a dual mode of action of the esters in the pancreatic
      islet B-cell, involving both the metabolic response to their sugar moieties and a
      direct effect of the esters themselves upon a specific receptor system. It is
      proposed that selected esters could be used as insulinotropic tools in non
      insulin-dependent diabetes mellitus.

PMID- 9523358
TI  - Effects of the nonsteroidal anti-inflammatory drug nimesulide on energy
      metabolism in livers from adjuvant-induced arthritic rats.
AB  - The effects of nimesulide on energy metabolism and the hepatic metabolic
      alterations produced by adjuvant-induced arthritis were investigated in the
      perfused rat liver an in isolated liver mitochondria. Nimesulide, at therapeutic
      levels (20-50 microM), produced: (1) stimulation of oxygen consumption in the
      perfused rat liver and in isolated mitochondria, (2) inhibition of
      gluconeogenesis; (3) reduction of ADP/O ratio and the respiratory control ratio
      and stimulation of glycogenolysis in the livers from healthy rats, but not in
      livers from arthritic rats. These results indicate that nimesulide acts as a
      mitochondrial uncoupler. The main alterations produced by adjuvant-induced
      arthritis were: higher rates of oxygen consumption in both perfused livers and
      isolated mitochondria, with no decrease in the efficiency of mitochondrial energy
      transduction; (2) decreased gluconeogenesis and lack of glycogenolytic response
      to uncouplers, but not to alpha 1-agonists. These data allow to conclude that
      nimesulide-induced impairment of energy metabolism should worsen the hepatic
      disturbances that are already associated with the adjuvant disease.

PMID- 9523359
TI  - Simultaneous determination of a new hepatoprotective agent, YH439, and its
      metabolites, M4, M5, and M7 in plasma and urine by high-performance liquid
      chromatography.
AB  - A high-performance liquid chromatographic method was developed for the
      simultaneous determination of YH439, and its metabolites (M4, M5, and M7) in
      human plasma and rat urine using testosterone as an internal standard. The method
      involved deproteinization (plasma sample) or extraction (urine sample) followed
      by injection onto a C18 reversed-phase column. The mobile phase was acetonitrile
      0.063 M phosphoric acidisopropyl alcohol (38:48:14, v/v/v), and the flow rate was
      1.0 ml/min for the two methods. The column effluent was monitored by a UV
      detector set at 317 nm. The detection limits for YH439, M4, M5, and M7 in human
      plasma were 50, 40, 50, and 50 ng/ml, respectively, using the deproteinization
      method, and the corresponding values in rat urine were 50, 100, 50, and 50 ng/ml
      using the extraction method. No interferences from endogenous substances were
      found.

PMID- 9523360
TI  - Determination of aloesin in plasma by high-performance liquid chromatography.
AB  - A high-performance liquid chromatographic method was developed for the
      determination of aloesin in human plasma. The method involved deproteinization of
      biological samples with 1 volume of each 0.04 M Ba(OH)2 and 10% ZnSO4 aqueous
      solution. A 50-microliter aliquot of the supernatant was injected onto a C18
      reversed-phase column. The mobile phase, methanol-H2O (20:80, v/v), was run at a
      flow-rate 1.5 ml/min. The column effluent was monitored by a ultraviolet detector
      at 254 nm. The retention time of aloesin was 7 min. The detection limit for
      aloesin in human plasma was 0.1 microgram/ml. The coefficient of variation of the
      assay was generally low (below 5.04%) for human plasma. No interferences from
      endogenous substances were observed.

PMID- 9523361
TI  - History of tuberculosis.

PMID- 9523362
TI  - Old versus new: nitroglycerin versus NO?

PMID- 9523363
TI  - Prescription of medications by primary care physicians in the light of asthma
      guidelines.
AB  - The purpose of this study was the evaluation of the extent of dissemination of
      asthma guidelines among primary health care physicians in Greece. Sixty-five of
      80 primary care physicians (response rate 80.2%) answered a questionnaire about
      asthma morbidity, manner of choice of treatment and asthma management plans. One
      out of 12 patients who were examined by a primary care physician suffered from
      bronchial asthma. Forty-two physicians treated their asthma patients according to
      the pulmonologist's recommendations, and only 15 prescribed asthma treatment
      according to asthma guidelines. beta 2-agonist inhalers and theophylline tablets
      represent 41% of all prescribed medicines in asthma and corticosteroid inhalers
      24% of medications. Eight physicians prescribed theophylline as the first and 20
      physicians corticosteroid inhalers as the third choice of medication in asthma
      treatment. Consequently, the prescription of beta 2-agonist inhalers and
      theophylline tablets seems to be higher than asthma guidelines recommend. Better
      dissemination of guidelines among specialists and primary health care physicians
      will hopefully make asthma management optimal.

PMID- 9523364
TI  - Indices of respiratory muscle endurance in healthy subjects.
AB  - BACKGROUND: The evaluation of respiratory muscle performance can be described in
      terms of strength and endurance, the latter usually being measured by means of
      resistive or threshold inspiratory loads, using devices that are also used for
      respiratory muscle training. Few authors, however, have published endurance
      reference values for healthy subjects. To that end, we studied two indices of
      respiratory muscle endurance in a population of 99 healthy volunteers (50 men, 49
      women) divided into five age groups (20-70 years old) applying a modification of
      the methods of Martyn et al. and Nickerson and Keens. Inspiratory muscle
      endurance (Tlim) was defined as the time the subject was able to sustain
      breathing against an inspiratory pressure load equivalent to 80% of the maximum
      tolerated load (Cmax). Cmax was calculated using a 2-min incremental threshold
      load. RESULTS: We found that the heaviest inspiratory threshold load tolerated
      for 2 min and the time a load equivalent to 80% of Cmax (Tlim) could be sustained
      were not significantly different for male and female subjects. Tlim correlated
      with Cmax, age, height, and maximum respiratory pressures.

PMID- 9523365
TI  - Hypoxic ventilatory responses and gas exchange in patients with Parkinson's
      disease.
AB  - Ventilatory responses to isocapnic, progressive hypoxic rebreathing (HVR), in
      supine and sitting positions, lung ventilation and gas exchange while breathing
      air and during 5 min of breathing 11% O2 in N2 were studied in 12 healthy young
      (20-28 years), 5 old (57-73 years) male subjects, and in 7 male patients with
      Parkinson's disease (PD) aged 55-67 years. The piecewise linear approximation
      technique was used for evaluation of the ventilatory response curves, which
      allowed a separate analysis of slopes during minor and severe hypoxia. It has
      been shown that body position affected HVR. In the range of PETO2 from 60 to 35
      mm Hg, the ventilatory response in the sitting position was higher than supine:
      in young persons by 43%, in healthy old persons by 76%, and in the PD patients by
      211%. No significant differences in HVR to minor hypoxia (PETO2 from 100 to 60 mm
      Hg) were found in the 3 groups. During severe hypoxia (PETO2 from 60 to 35 mm Hg)
      the slope of minute ventilation versus O2 was 4.6 (supine) and 2.6 (sitting)
      times greater in healthy old men than PD patients' slopes. PD patients compared
      to old controls had 32% lower alveolar ventilation, 10% lower PETO2 and 15%
      elevation of PETCO2 while breathing air; similar differences were found while the
      patients were breathing 11% O2. The reduced alveolar ventilation under severe
      hypoxia in patients with PD could not be attributed to mechanical restriction of
      lung function. We suggest that the discrepancy in HVR under minor and severe
      hypoxia results from dysfunction in chemoreception associated with Parkinsonism.

PMID- 9523366
TI  - Sarcoidosis: family contact study.
AB  - AIM: To assess the familial aggregation in sarcoidosis in our environment.
      METHODS: The medical centers of Catalonia (Spain) were approached to identify,
      retrospectively, patients diagnosed as sarcoidosis from 1986 to 1988. 245
      sarcoidosis cases were recorded (annual incidence: 1.36/100,000 inhabitants).
      Finally, in 1990 a telephone questionnaire was administered to 188 sarcoidosis
      cases. RESULTS: These cases reported 3,757 familial contacts, 5 of whom had
      confirmed sarcoidosis. The clinical presentation of familial sarcoidosis was
      similar to nonfamilial sarcoidosis, only Lofgren syndrome stood out. The
      prevalence of sarcoidosis among familial contacts was 1.33/1,000. CONCLUSIONS:
      The familial association is low and corresponds with the low annual incidence in
      our community.

PMID- 9523367
TI  - Slow compartment features and gas exchange impairment in mild asthma: effects of
      beta agonist inhalation.
AB  - Static and dynamic lung volumes, arterial blood gases, alveolar ventilation and
      ventilation-perfusion (VA/Q) relationships were studied in 14 mild asthmatic
      patients and in 7 normal subjects (as controls) before and after fenoterol
      inhalation. Multiple nitrogen washout curves were analyzed by a bicompartmental
      distribution model, in order to assess the distribution of ventilation and VA/Q
      mismatch. At baseline, asthmatics showed mild airway obstruction and gas exchange
      impairment [forced expiratory volume in 1 s (FEV1) = 79% pred; PaO2 = 87.4;
      alveolar-arterial oxygen tension gradient (AaPO2) = 22.9 mm Hg]. By analysing
      nitrogen washout curves, an alveolar slow space representing 45.1% of total lung
      volume (vs. 36.8% in normals; p = 0.044) was identified; its alveolar ventilation
      per minute per unit lung volume (VA2/L2) was lower than in normals (p = 0.01).
      beta-Agonist inhalation by the asthmatics, which reversed airway obstruction
      (FEV1 = 98% pred.; p < 0.001) and improved gas exchange (PaO2 = 92.6 mm Hg, p <
      0.001; AaPO2 = 16.8 mm Hg, p = 0.003), led to a highly significant increase in
      VA2/L2 (p = 0.001). The improvement in PaO2 was associated with the increase in
      VA2/L2 (r2 = 0.39; p = 0.017), but not with the increase in FEV1. Lastly, the
      changes in FEV1 and VA2/L2 were not correlated with each other. We conclude that
      even in mild stable asthma there is substantial unevenness of ventilation,
      detectable by bicompartmental analysis of nitrogen washout curves, which is
      responsible for gas exchange impairment and is not related to common spirometric
      parameters. In addition, the improvement in gas exchange is probably due to the
      effect of fenoterol on the tributary airways of the alveolar slow compartment.
      This effect can be assessed by this simple method, which can be used in clinical
      pharmacology studies and in the follow-up of asthmatic patients.

PMID- 9523368
TI  - CT bronchus sign-guided bronchoscopic multiple diagnostic procedures in
      carcinomatous solitary pulmonary nodules and masses.
AB  - CT bronchus sign (BS) designates a bronchus leading directly to a peripheral
      pulmonary lesion. The objective of this investigation is to determine the
      contribution of BS-guided bronchoscopic multiple diagnostic procedures (BMDPs) to
      the diagnostic yield of solitary nodules or masses (SPNMs) suspected of pulmonary
      carcinoma (PC). A prospective study was carried out in 92 patients with a 2-5 cm
      diameter SPNM at the level of third to fifth bronchial branching and without
      endobronchial tumors. Within 10 days after 2-mm CT scans were done, in each of
      92, bronchial washing (BW), brushing (BR), transbronchial needle aspiration
      (TBNA) and transbronchial lung biopsy (TBB) were performed respectively, via
      fiberoptic bronchoscopy (FB) under fluoroscopic guidance. In 40 (82%) of 49 with
      BS and in 19 (44%) of 43 without BS, FB established the diagnosis (p < 0.01). In
      84 cases of PC, BW, BR, TBNA and TBB provided the diagnostic yields of 4% (3),
      26% (22), 57% (48) and 49% (41), respectively; the combined yield reached 68%
      (57). A metastasis and a tuberculoma were diagnosed exclusively by TBB, and TBNA,
      respectively. All differences of diagnostic yield except that between TBNA and
      TBB (p > 0.05) were determined to be significant (p < 0.05). Thoracotomy verified
      diagnosis in 48 of 59 cases diagnosed and 19 of 33 undiagnosed by FB, and various
      tissue biopsies or clinical follow-up in 11 diagnosed and 14 undiagnosed by FB.
      The above data suggest that in the diagnosis of PC as a SPNM at the level of
      third-fifth bronchial branching, combining the guidance of CT BS, and BMDPs under
      fluoroscopic guidance can increase the yield considerably.

PMID- 9523369
TI  - Single breath diffusing capacity for carbon monoxide: effects of adjustment for
      inspired volume dead space, carbon dioxide, hemoglobin and carboxyhemoglobin.
AB  - In order to assess the additive effects of taking into account dead space volume
      (VD), carbon dioxide, hemoglobin (Hb) and carboxyhemoglobin on computation of
      single breath carbon monoxide diffusing capacity (DLCOsb), we sequentially
      applied all the corrections recommended by the 1987 American Thoracic Society
      (ATS) document on DLCOsb standardization. We used data from 739 men (333
      nonsmokers and 406 current smokers) and 475 women (403 nonsmokers and 72 current
      smokers) who underwent measurement of DLCOsb in the decade 1985-1994 at the Lung
      Function Laboratory of our institute. With respect to the unadjusted DLCOsb
      value, significant small differences were found for all the corrected formulas,
      ranging from -0.18 to 1.48 ml/min/mm Hg in men and from -0.24 to 1.57 ml/min/mm
      Hg in women. After computing the percent change of DLCOsb [(unadjusted-adjusted
      value) x 100/unadjusted value], we observed that the correction for VD caused an
      underestimation of DLCOsb of about 5.8% in men and 7.7% in women. However, when
      all the corrections were considered, these figures decreased to about 0.9% in
      males and 2.9% in females. Regarding specifically the correction for Hb, the
      adjusted value was slightly lower in men, while it was some-what higher in women,
      with respect to the unadjusted DLCOsb. In conclusion, the corrections suggested
      by ATS in the computation of DLCOsb, when considered altogether, seem to account
      for a limited proportion of test variability in usual clinical conditions,
      especially in males.

PMID- 9523370
TI  - Effects of inhalation of nitroglycerin on hypoxic pulmonary vasoconstriction.
AB  - Recent studies suggest that nitric oxide (NO) may play an important role in the
      pathophysiology of pulmonary hypertension. Nitroglycerin is metabolized to NO,
      which is a potent vascular smooth muscle relaxant. The aim of the present study
      was to compare the effects of inhaled and infused nitroglycerin on pulmonary
      hemodynamics and gas exchange in anesthetized, artificially ventilated dogs.
      Nitroglycerin was administrated either by inhalation or by infusion. Systemic
      blood pressure (SBP), pulmonary arterial pressure (PAP), and pulmonary capillary
      wedge pressure (PCWP) were measured, and cardiac output was estimated by an
      electromagnetic flowmeter. Blood gas measurements were performed during hypoxic
      gas exposure (FiO2; 0.1) with a continuous inhalation or infusion of
      nitroglycerin (1, 2.5 micrograms/kg/min). Inhaled (n = 4) and infused (n = 4)
      nitroglycerin (1 microgram/kg/min) did not produce any detectable effects on the
      hemodynamics. Inhaled nitroglycerin (2.5 micrograms/kg/min) reduced SBP, PAP and
      calculated pulmonary vascular resistance (PVR) in all dogs. Cardiac output did
      not change. In addition, inhaled nitroglycerin increased PaO2. In contrast, the
      continuous infusion of nitroglycerin (2.5 micrograms/kg/min) did not change in
      PAP, whereas infused nitroglycerin decreased the mean SBP. Infused nitroglycerin
      did not alter cardiac output and calculated PVR. A decreased PaO2 was noted in 2
      dogs on nitroglycerin infusion. These findings indicate that inhaled
      nitroglycerin effects the pulmonary circulation relatively more than infused
      nitroglycerin, which tends to have more of a general effect on the systemic
      circulation. The effects of inhaled nitroglycerin may thus be comparable to the
      effects of NO inhalation.

PMID- 9523372
TI  - Suppressive BALF lymphocyte phenotype in a patient with prolonged stable alveolar
      proteinosis.
AB  - The case history of a 25-year-old man suffering from idiopathic alveolar
      proteinosis is described. The patient showed a prolonged stable mild disease and
      a distinct suppressive phenotypic profile of BALF lymphocytes. Specifically, a
      low T4/T8 ratio and a high percentage of CD11b+ T8 lymphocytes was found.
      Correlations with disease expression are made.

PMID- 9523371
TI  - Effect of inhaled cyclosporin on the rat airway: histologic and bronchoalveolar
      lavage assessment.
AB  - Airway inflammation plays a pivotal role in asthma. Over the last 10 years,
      evidence has accumulated for the potential role of lymphocytes in airway
      inflammation. Since cyclosporin A (Cyc-A) can profoundly influence lymphocyte
      activation, it is appropriate to consider this drug as a novel antiasthmatic. The
      effect of inhalation of low doses of Cyc-A on airway inflammation remains
      unclear. The purpose of this study was to investigate the bronchoalveolar lavage
      (BAL), peripheral blood cell profiles, and lung biopsy specimens in Cyc-A
      pretreated rats. Twenty-nine rats (8 controls, 10 ovalbumin sensitized, and 11
      Cyc-A inhaling and ovalbumin sensitized) were included in the study. A commercial
      intravenous Cyc-A solution was given as a single dose of 20 mg/kg 1 h prior to
      inhalation of ovalbumin via nebulizer. The total number of BAL cells
      significantly increased in rats inhaling Cyc-A when compared with ovalbumin
      sensitized rats (2.37 +/- 2.34 x 10(6)/ml and 1.01 +/- 0.49 x 10(6)/ml
      respectively, p < 0.05). There was a significant increase in the percentage of
      lymphocytes (14.5 +/- 8.5 versus 27.4 +/- 7.4%, p < 0.03), a nonsignificant
      increase in the percentage of eosinophils (0.8 +/- 1.0 versus 3.0 +/- 4.6%), and
      a significant decrease in the percentage of polymorphonuclear leukocytes (9.4 +/-
      6.9 versus 3.4 +/- 3.8%, p < 0.01) and macrophages (75.4 +/- 5.1 versus 50.2 +/-
      11.8%, p < 0.02) in BAL in the ovalbumin-sensitized group as compared with
      controls. Differential cell counts revealed a higher percentage of neutrophils
      and macrophages in the BAL of Cyc-A-pretreated rats than in that of the ovalbumin
      sensitized group (26.3 +/- 26.8 versus 3.4 +/- 3.8%, p < 0.01 and 66.1 +/- 7.7
      versus 50.2 +/- 11.8%, p < 0.02). There was a nonsignificant decrease of
      lymphocytes and eosinophils in the Cyc-A-pretreated group when compared with the
      ovalbumin-sensitized group (27.4 +/- 7.4 versus 21.1 +/- 12.4 and 3.0 +/- 4.6%
      versus 2.4 +/- 2.6%). The peripheral blood total white blood cell count decreased
      in the ovalbumin-sensitized and Cyc-A-pretreated groups as compared with the
      control group (2,520 +/- 1,098/mm3, 3,591 +/- 2,251/mm3, and 5,975 +/- 2,787/mm3,
      respectively, p < 0.01). In addition, peripheral eosinophilia was detected in the
      Cyc-A-pretreated group when compared with controls and the ovalbumin-sensitized
      group (6.9 +/- 4.7, 2.4 +/- 1.1, and 2.6 +/- 2.4%, respectively, p < 0.01). Light
      microscopic examination of the airways revealed prominent eosinophilia in
      tracheal, bronchial, and bronchiolar sections in the ovalbumin-sensitized group:
      counts were 1.8 +/- 2.3/HPF, 10.3 +/- 11.4/HPF, 63.3 +/- 45.0/HPF, respectively.
      Cyc-A resulted in a decrease of the eosinophil counts/HPF to 0/HPF in trachea (p
      < 0.05), to 4.3 +/- 9.4/HPF in bronchi (p < 0.02), to 19.4 +/- 38.4 in
      bronchioles (p < 0.004). In conclusion, the present study supports the theory
      that locally administered inhaled low-dose Cyc-A is effective on inflammatory
      cells of sensitized airways and peripheral cells. It may therefore be useful in
      elucidating the inflammatory mechanisms involved in asthma.

PMID- 9523373
TI  - Parathyroid-hormone-related-protein-producing thymic carcinoma presenting as a
      giant extrathoracic mass.
AB  - A 53-year-old female with a 9-month history of chest pain presented with a giant
      anterior chest wall mass. Radiologic examination showed an anterior mediastinal
      tumor invading the chest wall. Serum calcium and parathyroid hormone-related
      protein (PTHrP) levels were extremely elevated. Biopsy specimens disclosed a
      squamous cell carcinoma with Hassall's corpuscle-like keratotic pearls, and an
      immunohistological study showed a positive staining with PTHrP. The tumor and
      serum PTHrP concentration markedly decreased following cisplatin-based
      chemotherapy and radiation. This is the first case of PTHrP producing a thymic
      carcinoma with the unusual presentation of a large extrathoracic mass.

PMID- 9523374
TI  - Treatment of chronic, refractory cough with baclofen.
AB  - Chronic, nonproductive cough may result from enhanced sensitivity of the cough
      reflex. Often, this debilitating symptom is refractory to standard antitussive
      therapy. Baclofen, an agonist of gamma-aminobutyric acid (GABA), has been shown,
      in animals, to have antitussive activity via a central mechanism. Recently, in
      normal subjects, we have demonstrated the ability of baclofen to inhibit
      capsaicin-induced cough, as well as cough due to angiotensin-converting enzyme
      (ACE) inhibitors. Herein, we describe two patients with chronic, refractory cough
      who obtained symptomatic improvement after a 14-day course of low-dose, oral
      baclofen, administered in a double-blind, placebo-controlled manner. In addition,
      both subjects demonstrated significant increases in cough threshold to inhaled
      capsaicin after treatment with baclofen.

PMID- 9523375
TI  - Effect of inhaled ingredients of a commercial cyclosporin A ampoule on airway
      inflammation.

PMID- 9523376
TI  - A true coin lesion.

PMID- 9523377
TI  - What is your diagnosis. Multiple pulmonary nodules.

PMID- 9523378
TI  - A plea for the use of standardized outcome measures in everyday practice.

PMID- 9523379
TI  - How should we treat primary hyperparathyroidism?

PMID- 9523380
TI  - Diagnostic value for rheumatoid arthritis of antiperinuclear factor at the 1:100
      threshold. Study of 600 patients and meta-analysis of the literature.
AB  - Six hundred sera from patients with chronic rheumatic diseases including 429 with
      rheumatoid arthritis were tested in a blind fashion for IgG antiperinuclear
      factor using an indirect fluorescent antibody assay on buccal cells. Using the
      dilution of 1:100 found to be optimal in an earlier study, 283 of the 429 (66%)
      rheumatoid arthritis sera and 22 of the 171 (13%) control sera were positive for
      antiperinuclear factor. Titers were higher in the rheumatoid arthritis group than
      in the control group. A meta-analysis of studies that used sera diluted 1:80 or
      1:100 (2853 sera including 939 from patients with rheumatoid arthritis, 1539 from
      patients with other rheumatic diseases and 375 from healthy controls or patients
      with unclassified rheumatic diseases) yielded a sensitivity of 0.75, a
      specificity of 0.93, and a positive predictive value of 0.87. These data
      demonstrate that antiperinuclear factor testing contributes usefully to the
      diagnosis of rheumatoid arthritis.

PMID- 9523381
TI  - Localization of the centromere protein CENP-B using scleroderma sera and evidence
      for a role in centromere survival.
AB  - OBJECTIVE: To determine whether centromeric CENP A, B and C proteins play a role
      in centromere survival. METHODS: Sixteen anti-centromere sera from scleroderma
      patients were used. The most common reactivity demonstrated by Western blot was
      anti-CENP-A, followed by anti-CENP-B and -C, in that order. The reactivity of
      these sera with HEp-2 cells was studied using an indirect immunofluorescence
      assay with and without prior digestion by a DNase, Aspergillus nuclease and the
      restriction endonucleases Bam HI, Hind III, and Eco RI. CENP-B was purified using
      affinity chromatography and anti-CENP-B antibody. The interaction between CENP-B
      and the CENP-B box was evaluated using immunoprecipitation. Precipitates
      containing alphaDNA were amplified using a PCR method with specific primers for
      the CENP-B box. RESULTS: None of the nucleases altered the fluorescence pattern.
      PCR amplification showed that CENP-B adsorbed on a Sepharose-4B/anti-CENP-B
      antibody column retained alphaDNA satellites. No retention was seen in the
      absence of CENP-B. CONCLUSIONS: CENP-B protects alphaDNA from digestion by
      nucleases and prevents DNase or restriction enzyme digestion from affecting the
      morphology and location of centromeres. CENP-B may promote and maintain joining
      of DNA satellites in the centromere.

PMID- 9523382
TI  - Sex hormones in spondylarthropathies. A study in 57 patients.
AB  - Studies of the hormonal status of patients with spondylarthropathies are few in
      number, despite the predominantly male sex ratio characteristic of these
      diseases. Most suggested an elevation in androgen levels. We determined the
      following parameters in 57 men with spondylarthropathies: FSH, LH, prolactin,
      estradiol, total testosterone, free testosterone, delta-4-androstenedione, 17-OH
      progesterone, estradiol over total testosterone ratio and estradiol over free
      testosterone ratio. Results were compared to those in a group of 100 healthy
      controls. Mean patient age was 41.9 years, and mean disease duration was one
      year. None of the patients were under corticosteroid therapy. The mean prolactin
      level was normal (8.4 +/- 4.5 ng/ml), whereas the mean 17-OH-progesterone level
      was significantly elevated (2.02 +/- 0.8 ng/ml). The estradiol over testosterone
      ratios were normal. This hormone profile is consistent with partial deficiency in
      the enzyme 21-hydroxylase, which is encoded by a gene located on chromosome 6
      only 600 kb away from the HLA B locus. We suggest that some class I alleles may
      be associated with an alteration in 21-hydroxylase responsible for an increase in
      17-OH-progesterone levels and for macrophage inhibition resulting in delayed
      elimination of antigens. This hypothesis is consistent with the possibility
      raised by others that macrophage inhibition may explain the increased prevalence
      of infections due to intracellular organisms in patients with
      spondylarthropathies.

PMID- 9523383
TI  - Abnormalities of the adult shoulder due to sickle cell osteonecrosis during
      childhood.
AB  - PATIENTS AND METHODS: A retrospective study of 110 adults with sickle cell anemia
      (SS genotype) was conducted to determine the frequency of complications of sickle
      cell osteonecrosis of the shoulder in childhood. The glenohumeral joint was
      evaluated on plain anteroposterior and lateral radiographs of the shoulder.
      RESULTS: Mean time since osteonecrosis of the shoulder was 24 years. Radiographic
      abnormalities were seen in 106 of the 220 shoulders (48.2%). Both shoulders were
      affected in 86% of cases and at least one hip in 96%. Radiographic abnormalities
      included isolated caput magna, caput plana, a short humeral neck and ascension of
      the tuberosities. Twelve shoulders exhibited glenoid fossa abnormalities, which
      consisted in complete or partial hypoplasia. Evidence of glenohumeral
      osteoarthritis was seen in 11 shoulders. DISCUSSION: The shoulder abnormalities
      seen in our patients were probably due to growth disturbances in the proximal
      humerus secondary to osteonecrosis of the humeral head during childhood. They
      were common but less likely to produce functional impairment than osteonecrosis
      related lesions of the hip. However, some patients had premature osteoarthritis
      and geometric shoulder abnormalities responsible for functional loss in
      adulthood.

PMID- 9523385
TI  - Harmful effects of the placebo-controlled design.

PMID- 9523384
TI  - Psychosocial and occupational impact of chronic low back pain.
AB  - The significant psychosocial and occupational impact of low back pain is a risk
      factor for chronicization but remains difficult to be evaluated. METHODS: A cross
      sectional study of acute and chronic low back pain patients managed by 1282
      physicians was conducted using an 85-item questionnaire. Most items were composed
      of multiple or binary clauses. A semi quantitative six-point scale was used to
      evaluate effects of the pain on family and personal life. A total of 2741
      completed questionnaires were sent in. The present study was conducted on the
      1072 questionnaires completed for "active" (as opposed to retired) patients with
      chronic low back pain. Mean age was 44 years. RESULTS AND DISCUSSION: As compared
      to the general population, there were fewer blue-collar workers, executives, and
      skilled professionals and more intermediate professions (34% versus 19% according
      to an INSEE survey, p < 0.001). Twelve per cent of patients were able either to
      change jobs or to find lighter duties in their current job, but a similar
      proportion were completely incapacitated or awaiting a job modification.
      Significant negative effects on everyday life were reported by 80% of patients,
      on emotional life by 58%, and on sexual activity by 46%. Most patients had
      reduced their leisure and household activities. Psychological disorders were
      noted in 75% of patients. On the day of the visit, two-thirds of patients were
      given a prescription for analgesics, nonsteroidal antiinflammatory drugs, and/or
      muscle relaxants, whereas only 34% received advice regarding their diet and life
      style and only 4% were sent to a back school. Despite significant effects on
      everyday and personal experiences associated with an increased risk of
      chronicization, treatments given to low back pain patients consist mainly of
      symptomatic medication.

PMID- 9523386
TI  - Ro(SS-A) and anti-Ro(SS-A): an update.
AB  - Anti-Ro/SSA antibodies are the antinuclear antibodies most commonly found in
      everyday clinical practice and are closely associated with Sjogren's syndrome,
      systemic lupus erythematosus and neonatal lupus. They play a pathogenic role in a
      variety of clinical manifestations, including skin lesions and neonatal lupus
      heart block. Autoantibodies to Ro(SS-A) recognize a ribonucleoprotein complex
      composed of small single-stranded RNAs (hYRNAs) and of one or more peptides. Four
      molecular forms of this complex have been differentiated based on the nature of
      the peptide: a lymphocyte and an erythrocyte Ro with a 60 kDa peptide, a
      lymphocyte Ro with a 52 kDa peptide and an erythrocyte Ro with a 54 kDa peptide.
      The Ro complex is found in most tissues and cells (erythrocytes, platelets), with
      differences in structure and quantity across tissues, species and embryonic
      development stages. Although its function remains unknown, its ability to bind
      nucleic acids and the fact that it shares homologies with gene regulation
      proteins suggest that it may participate in RNA transcription processes. A number
      of environmental factors (exposure to ultraviolet radiation, viral infections)
      may cause translocation of the Ro complex to nucleocytoplasmic and membrane sites
      where it is not normally found, thereby leading to the development of
      autoimmunity. The structure of the Ro(SS-A)-hYRNA complex and the development of
      autoimmunity are currently the focus of active research efforts that can be
      expected to improve our understanding of the clinical manifestations directly
      related to anti-Ro(SS-A) antibodies.

PMID- 9523387
TI  - Third-degree atrioventricular block in a patient under chloroquine therapy.
AB  - The first case of chronic cardiac toxicity due to an antimalarial agent was
      reported in 1971 and since then several cases of heart failure, restrictive
      cardiomyopathy or atrioventricular block have been ascribed to this family of
      drugs. We report the case of a 43-year-old woman who developed juvenile chronic
      arthritis at the age of ten, followed in adulthood by sero-positive rheumatoid
      arthritis. In 1980 she was put under chloroquine sulfate (hydroxychloroquine was
      not available) in a dose of 200 mg/d (152.66 mg of chloroquine), with 10 mg/day
      of prednisone. She developed myalgia and increased skin pigmentation, but
      disregarded recommendations that these symptoms required discontinuation of
      chloroquine therapy. She was lost to follow-up, but continued the chloroquine
      therapy of her own accord. In December 1993, she developed a third-degree
      atrioventricular block with syncopes requiring implantation of a pacemaker. The
      rare but well-documented myopathy induced by antimalarial agents can produce
      early severe lesions of the cardiac muscle, which may have a predilection for the
      interventricular septum, explaining the risk of atrioventricular block. Although
      histologic studies were not performed in our patient, the clinical evidence of
      toxicity, absence of underlying heart disease and fairly young age of the patient
      pointed to chloroquine toxicity. Periodic cardiac investigations including
      electrocardiography may be warranted in patients under antimalarial therapy.

PMID- 9523388
TI  - Sudden cochlear hearing loss in a patient with Behcet's disease.
AB  - A Behcet's disease patient developed sudden cochlear hearing loss during a flare
      of her disease. Prednisone and cyclosporin therapy was ineffective, probably
      because it was initiated late. Sensorineural hearing loss is a rare but
      underrecognized complication of various forms of vasculitis such as Wegener's
      granulomatosis, polyarteritis nodosa, giant cell arteritis and Behcet's disease.
      Its importance lies in the need for an early diagnosis, since prompt treatment
      with steroids and immunosuppressive agents may lead to restoration of hearing.

PMID- 9523389
TI  - Bronchiolitis obliterans organizing pneumonia in a patient with rheumatoid
      arthritis.
AB  - A 75-year old man with rheumatoid arthritis developed bronchiolitis obliterans
      organizing pneumonia (BOOP), which responded to treatment with prednisolone (1
      mg/kg/d) and cyclophosphamide (100 mg/d).

PMID- 9523390
TI  - Two cases of discitis due to Propionibacterium acnes.
AB  - We report two cases of discitis due to Propionibacterium acnes and review
      previously published cases of bone and joint infections in which this organism
      was recovered as a pure culture. P. acnes is an anaerobic organism usually
      considered a normal inhabitant of the skin but capable of producing a variety of
      infections including discitis, osteitis, arthritis, and chest wall osteitis. Most
      patients were immunocompetent. A few infections occurred spontaneously, whereas
      others were secondary to a break in the skin or to implantation of foreign
      material into the body for instance during internal fixation of a fracture or
      arthroplasty. Cases of P. acnes chest wall infection have been reported in
      patients with palmoplantar pustulosis or chronic or multifocal osteitis,
      supporting a role for P. acnes in SAPHO syndrome.

PMID- 9523392
TI  - Metastasis from a glioblastoma and Staphylococcus aureus spondylitis in the same
      vertebral body.

PMID- 9523391
TI  - Frozen shoulder: a new delayed complication of protease inhibitor therapy? .
AB  - We report three cases of frozen shoulder (including one with bilateral
      involvement) in human immunodeficiency virus (HIV)-positive patients under triple
      antiretroviral therapy. In each case, the diagnosis was confirmed by
      arthrography, and the classic causes of frozen shoulder were ruled out. We
      suggest that protease inhibitor therapy may have contributed to the development
      of frozen shoulder in these patients. Long-term follow-up of the increasing
      numbers of patients under triple antiretroviral therapy will confirm or refute
      this hypothesis.

PMID- 9523393
TI  - Aspergillus osteomyelitis. Report of a case investigated by magnetic resonance
      imaging.

PMID- 9523394
TI  - Isolated polyarthritis followed by systemic polyangiitis with antineutrophil
      cytoplasmic antibody.

PMID- 9523395
TI  - Neonatal immunology.
AB  - The neonate, whether premature or of normal gestational age, is a unique host
      from an immunologic perspective. Many components of the immune system function
      less well in neonates compared with adults, giving rise to the concept of an
      "immunodeficiency of immaturity." The adaptive significance of these alterations
      for neonatal survival remains obscure. This review highlights some of the most
      prominent quantitative and qualitative differences between neonatal and adult
      immune systems. From a clinical standpoint, the most important differences appear
      to be (1) reduction in the available bone marrow reserve of granulocyte
      precursors, (2) reduction in serum complement activity, (3) decreased ability to
      produce antibodies against bacterial polysaccharide antigens, and (4) increased
      percentage of T lymphocytes bearing an antigenically "naive" cell surface
      phenotype and a correspondingly naive functional program.

PMID- 9523396
TI  - Early onset neonatal bacterial infections.
AB  - The evaluation of a neonate with suspected sepsis is one of the most common, most
      demanding, and most important tasks of the pediatrician or neonatologist. This
      review summarizes the difficulties in the prompt diagnosis of neonatal sepsis and
      the appropriate utilization of screening laboratory tests of blood, urine, and
      cerebrospinal fluid in this setting. The appropriate utilization of these
      laboratory tests requires careful consideration of the inherent limitations and
      appreciation of the sensitivity and specificity of these tests for the diagnosis
      of early onset bacteremia and sepsis.

PMID- 9523397
TI  - Neonatal nosocomial infections.
AB  - Nosocomial acquisition of infection is now the most common mode of transmission
      of infection in neonatal intensive care units (NICUs). Surveillance studies have
      shown rates of infection in the NICU of 15% to 20%, which are as high as those in
      adult medical or surgical ICUs and higher than those in most pediatric ICUs.
      Studies of NICU nosocomial infections have pinpointed the use of indwelling
      vascular catheters, high-calorie hyperalimentation infusions, assisted
      ventilation, and prior use of antibiotics as significant risk factors for
      infection. Strategies to reduce nosocomial infections with the use of
      prophylactic antibiotics, immunoglobulins, and physical barriers have been
      unsuccessful. New methods of reducing risk factors and enhancing the neonate's
      resistance to infection are badly needed.

PMID- 9523398
TI  - Prophylaxis for neonatal group B streptococcus infections.
AB  - For the past two decades, group B streptococcus (GBS) has been the pathogen most
      frequently isolated from neonates with invasive bacterial disease. This is a
      review of the relevant aspects of microbiology, epidemiology, and clinical
      manifestations and a summary of the major studies of prevention strategies that
      led to the development of the 1996 consensus guidelines for prevention of
      perinatal GBS disease. There is now sufficient experience to know that > or = 80%
      of cases of early onset GBS disease can be prevented when a protocol for
      intrapartum chemoprophylaxis with either penicillin or ampicillin is implemented
      consistently within a delivery population. Present controversies revolve around
      the choice between a universal screening-based strategy versus a risk factor
      based strategy, optimal management of the neonate born to a mother who received
      intrapartum antimicrobial prophylaxis, and effective methods to ensure
      implementation. The present guidelines will likely be refined as additional
      experience is gained.

PMID- 9523399
TI  - The role of intravenous immunoglobulin for the prevention and treatment of
      neonatal sepsis.
AB  - The use of intravenous immunoglobulin (IVIG) for the prevention and treatment of
      sepsis in neonates is appealing because of the relative immunodeficiency of the
      neonate and the desire to improve the relatively poor outcome even with optimal
      antimicrobial treatment. The effectiveness of IVIG for these uses has been
      studied in numerous prospective as well as retrospective small and large trials
      that have had discordant conclusions. Meta-analysis demonstrates the marginal but
      significant benefit of prophylactic IVIG administered shortly after birth in
      preventing early onset sepsis in premature low birth weight newborns (P = .0193,
      two-sided). The expense of prophylactic use of IVIG administration for the
      relatively large premature newborn population given the minimal benefit as
      demonstrated by original studies and by meta-analysis is not justified. In
      contrast, meta-analysis of studies of IVIG for the treatment of neonates with
      sepsis shows a significant and unequivocal sixfold decrease in the mortality rate
      (P = .007, two-sided) when IVIG is administered in addition to standard
      therapies. The additional benefit of decreasing the risk for acute mortality
      indicates that the inclusion of IVIG should be considered a part of the routine
      therapy of neonatal sepsis.

PMID- 9523400
TI  - Neonatal herpes simplex virus infections.
AB  - Neonatal herpes simplex virus (HSV) infection is one of the life-threatening
      infections of newborns. It affects approximately 1,500 to 2,200 infants per year
      in the United States. Changes in the presentation of neonatal HSV infection over
      the past two decades include an increase in the frequency of skin, eye, and mouth
      (SEM) disease with a relatively unchanged rate of central nervous system (CNS)
      disease, but a relative decline in disseminated infection. Although the mortality
      of neonatal HSV infections has declined with current antiviral therapy, the
      mortality rate in CNS disease (15%) and disseminated disease (57%) remains high.
      Morbidity has been seen most frequently in infants with CNS and disseminated
      disease, with seizures or infection with HSV-2 determined to be risk factors for
      poor outcome in survivors. In a multicenter, randomized, blinded study by the
      Collaborative Antiviral Study Group, no differences in outcome were seen between
      neonates treated with vidarabine and acyclovir. More recently, administration of
      oral acyclovir has been demonstrated to prevent cutaneous recurrences of HSV
      after neonatal SEM disease. Although promising, this investigational protocol
      requires further evaluation before a routine recommendation for prophylactic
      therapy with oral acyclovir can be made. The application of polymerase chain
      reaction to rapid diagnosis of neonatal HSV disease may provide additional
      information on which clinical decisions may be based, but its diagnostic utility
      outside the research setting is still unproven. Further clinical trials for
      prophylaxis of recurrent SEM disease, prophylactic therapy for the prevention of
      recurrences of CNS or disseminated disease, the appropriate use of rapid
      diagnostic testing, and future therapies that may include passive antibody plus
      antiviral therapy or higher dosage and longer duration of antiviral therapy need
      to be evaluated.

PMID- 9523401
TI  - Medical management of the pregnant woman infected with human immunodeficiency
      virus type 1 and her child.
AB  - Heterosexual contact and intravenous drug use continue to result in new cases of
      human immunodeficiency virus type 1 (HIV-1) infection among adolescents and women
      of childbearing age. In North American and European surveys, 0.1% to 0.3% of
      childbearing women are infected with HIV; rates are 10 to 20 times higher in some
      inner-city areas. Timely, comprehensive, and well-coordinated care of the
      pregnant HIV-infected mother offers a unique opportunity to significantly
      influence two lives simultaneously. The mother can be offered therapeutic and
      prophylactic agents to treat her own infection, including antiretroviral therapy,
      which has been shown to markedly reduce the risk of vertical HIV-1 transmission.
      Recent advances in diagnostic virology now make it possible to definitively
      identify by 3 to 4 months of age those infants who are infected with HIV. Infants
      infected with HIV can be offered effective prophylaxis against Pneumocystis
      carinii pneumonia, which has dramatically reduced the incidence of this once
      common infection. Infected infants also should be monitored closely to institute
      antiretroviral therapy, and to diagnose and treat opportunistic and intercurrent
      infections and other acquired immunodeficiency syndrome-defining illnesses in a
      timely way.

PMID- 9523402
TI  - Respiratory syncytial virus immunoglobulin and monoclonal antibodies in the
      prevention and treatment of respiratory syncytial virus infection.
AB  - Respiratory syncytial virus (RSV) infection is particularly severe in infants
      with bronchopulmonary dysplasia (BPD) and in premature infants without BPD.
      Attempts to develop a vaccine against RSV have been unsuccessful. Passive
      immunoprophylaxis of premature infants with or without BPD using a hyperimmune
      human globulin against RSV (RSVIg) decreases the severity of RSV infection such
      that the rate of hospitalization following infection is reduced by 40%. The
      severity of illness among hospitalized infants is also reduced. To avoid the
      difficulties associated with intravenous infusion of immunoglobulins, monoclonal
      IgG antibodies against the fusion protein of RSV have been developed. In one
      trial, the antibodies were ineffective, although subsequent trials using higher
      doses of the antibody show more promising results. Studies of IgA monoclonal
      antibodies directed against RSV, which are administered in the form of nose
      drops, are also in progress. None of these preparations appear to be effective in
      the treatment of established RSV infection. Each of the preparations appeared to
      be safe, with one exception. Infants with cyanotic heart disease who received
      RSVIg had an increased risk of surgical complications, perhaps related to
      increases in serum viscosity as a result of receiving the hyperimmunoglobulin
      monthly in doses of 750 mg/kg. While definitive cost/benefit analyses are
      pending, RSVIg may be useful in infants and children with BPD who have current or
      recent oxygen requirements, as well as in certain premature infants without BPD.
      Recommendations on the use of RSVIg are provided.

PMID- 9523403
TI  - Primary extinction in cylinders and spheres
AB  - By transforming the Takagi equations into a representation using angular
      coordinates, it is in principle possible to obtain analytical expressions for the
      coefficients in a series expansion for the primary extinction factor in perfect
      crystals with a circular diffraction plane. In practice, it has been possible to
      obtain the first five terms in the expansion. This involves establishing
      recurrence relations for the families of Bragg and Laue boundary-value Green
      functions combined with integrations over the entrance and exit surfaces. The
      calculations, which cover the whole range of values for the scattering angle,
      theta oh, are performed using the mathematical software systems Mathematica and
      Maple.

PMID- 9523404
TI  - Absorption and weighted path lengths in cylinders and spheres
AB  - By using the boundary-value Green-function technique for the Takagi equations, it
      is possible to calculate the normal absorption factor and weighted path length in
      cylinders and spheres as double integrals in angular coordinates of well defined
      functions. The results are easy to implement for numerical computations. Exact
      analytical expressions for both crystal geometries are found in the limits of the
      Bragg angle theta oh-->0 degree and theta oh-->90 degrees.

PMID- 9523405
TI  - Fiber diffraction patterns for general unit cells: the cylindrically projected
      reciprocal lattice
AB  - The positions of reflections on the diffraction pattern from a polycrystalline
      fiber are described by a cylindrical projection of the reciprocal lattice. The
      characteristics of the projection depend on the crystal system and the
      orientation of the fiber axis relative to the unit-cell axes. Expressions
      describing the cylindrically projected reciprocal lattice for a general triclinic
      system and any orientation of the fiber axis are derived. Calculations using
      these expressions illustrate characteristics of the projected reciprocal lattice
      and aid in the interpretation of fiber diffraction patterns.

PMID- 9523406
TI  - Saying no to unwanted thoughts: self-focus and the regulation of mental life.
AB  - Drawing from models of mental control and cognitive self-regulation, it was
      hypothesized that heightened self-focus would promote the spontaneous suppression
      of social stereotypes. Participants who were induced to experience heightened
      self-focus indeed produced less stereotypic descriptions of social targets
      (Studies 1-4). Study 5 further demonstrated that self-focus produced reductions
      in stereotyping only among those participants whose personal standards dictated
      stereotype avoidance. A final study demonstrated that these spontaneous forms of
      stereotype suppression can produce a rebound effect, in which the magnitude of
      stereotyping increases markedly after a period of suppression. These findings are
      considered in the context of contemporary issues in mental control and social
      stereotyping.

PMID- 9523407
TI  - Terror management and aggression: evidence that mortality salience motivates
      aggression against worldview-threatening others.
AB  - The hypothesis that mortality salience (MS) motivates aggression against
      worldview-threatening others was tested in 4 studies. In Study 1, the
      experimenters induced participants to write about either their own death or a
      control topic, presented them with a target who either disparaged their political
      views or did not, and gave them the opportunity to choose the amount of hot sauce
      the target would have to consume. As predicted, MS participants allocated a
      particularly large amount of hot sauce to the worldview-threatening target. In
      Studies 2 and 3, the authors found that following MS induction, the opportunity
      to express a negative attitude toward the critical target eliminated aggression
      and the opportunity to aggress against the target eliminated derogation. This
      suggests that derogation and aggression are two alternative modes of responding
      to MS that serve the same psychological function. Finally, Study 4 showed that MS
      did not encourage aggression against a person who allocated unpleasant juice to
      the participant, supporting the specificity of MS-induced aggression to worldview
      threatening others.

PMID- 9523408
TI  - Turning up the contrast: self-enhancement motives prompt egocentric contrast
      effects in social judgments.
AB  - Contrast effects occur when people judge the behavior and attitudes of others
      relative to their own. We tested a motivational account suggesting that these
      effects arise because people tailor their judgments of others to affirm their own
      self-worth. Consistent with that interpretation, participants displayed more
      egocentric contrast in their judgments of another person's intelligence (i.e.,
      their evaluation of his score on the Scholastic Aptitude Test was more negatively
      related to their own score) after their self-esteem was threatened than after it
      was bolstered (Studies 1 and 2). High-self-esteem individuals displayed more
      judgmental contrast overall than did their low-esteem counterparts (Study 2).
      Strongly pro-choice participants whose esteem was threatened also displayed more
      contrast in their judgments of another person's attitude on abortion, relative to
      esteem-bolstered participants (Study 3). Discussion centers on the implications
      of these findings for theory on social comparison, self-affirmation, and social
      judgment.

PMID- 9523409
TI  - Feedback to minorities: evidence of a positive bias.
AB  - This research tested the prediction that Whites supply more lenient feedback to
      Blacks than to fellow Whites. In Study 1, White undergraduates were led to
      believe that they were giving feedback on essays written by either a Black or a
      White fellow student. As predicted, feedback was less critical when the supposed
      feedback recipient was Black rather than White. It was also predicted that the
      feedback bias would be selective for subjective evaluative domains (i.e., essay
      content) in contrast to objective evaluative domains (i.e., essay mechanics). An
      interaction between recipient race and evaluative domain confirmed this
      prediction. The domain-specific quality of the feedback bias suggests that the
      bias may arise from social motives rather than from more automatic processes.
      Study 2 replicated these results.

PMID- 9523410
TI  - Self-promotion as a risk factor for women: the costs and benefits of
      counterstereotypical impression management.
AB  - Three experiments tested and extended recent theory regarding motivational
      influences on impression formation (S. T. Fiske & S. L. Neuberg, 1990; J. L.
      Hilton & J. M. Darley, 1991) in the context of an impression management dilemma
      that women face: Self-promotion may be instrumental for managing a competent
      impression, yet women who self-promote may suffer social reprisals for violating
      gender prescriptions to be modest. Experiment 1 investigated the influence of
      perceivers' goals on processes that inhibit stereotypical thinking, and reactions
      to counterstereotypical behavior. Experiments 2-3 extended these findings by
      including male targets. For female targets, self-promotion led to higher
      competence ratings but incurred social attraction and hireability costs unless
      perceivers were outcome-dependent males. For male targets, self-effacement
      decreased competence and hireability ratings, though its effects on social
      attraction were inconsistent.

PMID- 9523411
TI  - On self-aggrandizement and anger: a temporal analysis of narcissism and affective
      reactions to success and failure.
AB  - Narcissists are thought to display extreme affective reactions to positive and
      negative information about the self. Two experiments were conducted in which high
      and low-narcissistic individuals, as defined by the Narcissistic Personality
      Inventory (NPI), completed a series of tasks in which they both succeeded and
      failed. After each task, participants made attributions for their performance and
      reported their moods. High-NPI participants responded with greater changes in
      anxiety, anger, and self-esteem. Low self-complexity was examined, but it neither
      mediated nor moderated affective responses. High-NPI participants tended to
      attribute initial success to ability, leading to more extreme anger responses and
      greater self-esteem reactivity to failure. A temporal sequence model linking self
      attribution and emotion to narcissistic rage is discussed.

PMID- 9523412
TI  - Sex differences in emotion: expression, experience, and physiology.
AB  - Although previous studies of emotional responding have found that women are more
      emotionally expressive than men, it remains unclear whether men and women differ
      in other domains of emotional response. We assessed the expressive, experiential,
      and physiological emotional responses of men and women in 2 studies. In Study 1,
      undergraduates viewed emotional films. Compared with men, women were more
      expressive, did not differ in reports of experienced emotion, and demonstrated
      different patterns of skin conductance responding. In Study 2, undergraduate men
      and women viewed emotional films and completed self-report scales of
      expressivity, gender role characteristics, and family expressiveness. Results
      replicated those from Study 1, and gender role characteristics and family
      expressiveness moderated the relationship between sex and expressivity.

PMID- 9523413
TI  - Can the promise of reward increase creativity?
AB  - Two experiments, involving 436 preadolescent schoolchildren, investigated how the
      explicitness of promised reward affects creativity. In the first study, the
      nonspecific promise of reward increased the creativity of picture drawing if
      children had previously received divergent-thinking training (generating novel
      uses for physical objects). In the second study, promised reward increased the
      creativity of children's drawings if current task instructions clarified the
      necessity of creative performance. Promised reward evidently increases creativity
      if there is currently, or was previously, an explicit positive relationship
      between creativity and reward.

PMID- 9523414
TI  - The relationship between racial identity and self-esteem in African American
      college and high school students.
AB  - The Multidimensional Model of Racial Identity was used to examine the
      relationship between racial identity and personal self-esteem (PSE) in a sample
      of African American college students (n = 173) and a sample of African American
      high school students (n = 72). Racial identity was assessed using the Centrality
      and Regard scales of the Multidimensional Inventory of Black Identity, whereas
      the Rosenberg Self-Esteem Scale was used to assess PSE. Four predictions were
      tested: (a) racial centrality is weakly but positively related to PSE; (b)
      private regard is moderately related to PSE; (c) public regard is unrelated to
      PSE; and (d) racial centrality moderates the relationship between private regard
      and PSE. Multiple regression analysis found that racial centrality and public
      racial regard were unrelated to PSE in both samples. Private regard was
      positively related to PSE in the college sample. Racial centrality moderated the
      relationship between private regard and PSE in both samples, such that the
      relationship was significant for those with high levels of centrality but
      nonsignificant for those with low levels.

PMID- 9523415
TI  - Symbolic immortality and the management of the terror of death: the moderating
      role of attachment style.
AB  - Three studies were designed to examine the contribution of R. J. Lifton's (1979)
      symbolic immortality construct to the management of the terror of death and to
      investigate whether attachment style may underlie this contribution. Using a
      sample of 420 Israeli students, Study 1 revealed an inverse correlation between
      self-reports of symbolic immortality and fear of personal death. This finding was
      validated in Study 2 (N = 120), which found that high symbolic immortality
      reduced the effects of a death salience manipulation on the level of punishment
      given to a social transgressor. Study 3 (N = 270) refined the association between
      symbolic immortality and fear of death. The inverse correlation found in Study 1
      was revealed only among securely attached persons. The discussion emphasizes the
      interconnectedness between personality, symbolic immortality, and the management
      of the terror of death.

PMID- 9523416
TI  - Personal resilience, cognitive appraisals, and coping: an integrative model of
      adjustment to abortion.
AB  - We hypothesized that the effects of personality (self-esteem, control, and
      optimism) on postabortion adaptation (distress, well-being, and decision
      satisfaction) would be fully mediated by preabortion cognitive appraisals (stress
      appraisals and self-efficacy appraisals) and postabortion coping. We further
      proposed that the effects of preabortion appraisals on adaptation would be fully
      mediated by postabortion coping. Results of a longitudinal study of 527 women who
      had first-trimester abortions supported our hypotheses. Women with more resilient
      personalities appraised their abortion as less stressful and had higher self
      efficacy for coping with the abortion. More positive appraisals predicted greater
      acceptance/reframing coping and lesser avoidance/denial, venting, support
      seeking, and religious coping. Acceptance-reframing predicted better adjustment
      on all measures, whereas avoidance-denial and venting related to poorer
      adjustment on all measures. Greater support seeking was associated with reduced
      distress, and greater religious coping was associated with less decision
      satisfaction.

PMID- 9523417
TI  - Ambivalence over emotional expression and reading emotions in situations and
      faces.
AB  - Three studies explored the relation of ambivalence over emotional expression (AE)
      and emotional expressiveness (EE) to reading the emotions of others. In Study 1
      (N = 340, 110 men), AE positively correlated and EE negatively correlated with
      self-reported confusion in reading others' emotions. In Studies 2 and 3,
      participants wrote descriptions of the emotions likely to be felt by a person in
      an emotional scenario or in a slide of a universal facial expression.
      Descriptions were content analyzed for emotion words. Results revealed
      significant AE x EE interactions. In both studies, inexpressive ambivalent
      individuals used emotion words of the opposite valence of that implied in the
      scenes or expressions. Implications for social relationships are discussed.

PMID- 9523418
TI  - The sense of control as a moderator of social class differences in health and
      well-being.
AB  - The authors examined social class differences in 2 aspects of the sense of
      control (mastery and perceived constraints) in 3 national probability samples of
      men and women ages 25-75 years (N1 = 1,014; N2 = 1,195; N3 = 3,485). Participants
      with lower income had lower perceived mastery and higher perceived constraints,
      as well as poorer health. Results of hierarchical multiple regression analyses
      showed that for all income groups, higher perceived mastery and lower perceived
      constraints were related to better health, greater life satisfaction, and lower
      depressive symptoms. However, control beliefs played a moderating role;
      participants in the lowest income group with a high sense of control showed
      levels of health and well-being comparable with the higher income groups. The
      results provided some evidence that psychosocial variables such as sense of
      control may be useful in understanding social class differences in health.

PMID- 9523419
TI  - Self-control as limited resource: regulatory depletion patterns.
AB  - If self-regulation conforms to an energy or strength model, then self-control
      should be impaired by prior exertion. In Study 1, trying to regulate one's
      emotional response to an upsetting movie was followed by a decrease in physical
      stamina. In Study 2, suppressing forbidden thoughts led to a subsequent tendency
      to give up quickly on unsolvable anagrams. In Study 3, suppressing thoughts
      impaired subsequent efforts to control the expression of amusement and enjoyment.
      In Study 4, autobiographical accounts of successful versus failed emotional
      control linked prior regulatory demands and fatigue to self-regulatory failure. A
      strength model of self-regulation fits the data better than activation, priming,
      skill, or constant capacity models of self-regulation.

PMID- 9523420
TI  - Regulating responses to anger: effects of rumination and distraction on angry
      mood.
AB  - Previous research has found that self-focused rumination maintains or increases
      depressed mood, whereas distraction decreases depressed mood (S. Nolen-Hoeksema &
      J. Morrow, 1993; S. Nolen-Hoeksema, J. Morrow, & B. L. Fredrickson, 1993). The
      present series of experiments examined these mood regulation strategies in the
      context of an angry mood. In Experiments 1 and 3, rumination increased anger,
      whereas distraction decreased or had no effect on anger. In Experiments 2 and 4,
      women were more likely to choose to ruminate when in a neutral mood but to
      distract themselves following induction of an angry mood. Men were equally likely
      to choose rumination or distraction, regardless of mood condition. The results
      are interpreted and discussed within the framework of an associative-network
      model of anger.

PMID- 9523421
TI  - Genetic and environmental influences on MMPI factor scales: joint model fitting
      to twin and adoption data.
AB  - In general, the shared family environment appears to play a negligible role in
      determining individual differences in personality and interests. Nevertheless,
      scattered reports of significant shared environmental influence on such variables
      appear in the literature. Using data from the Texas Adoption Project (TAP), the
      current study attempted to replicate twin study findings of significant shared
      environmental variance on four of nine Minnesota Multiphasic Personality
      Inventory (MMPI) factor scales (Rose, 1988). Conventional behavioral genetic
      analyses of the adoption data agreed in affirming a significant shared
      environmental influence on individual differences in Religious Orthodoxy only.
      Subsequent simultaneous modeling of Rose's twin data and TAP adoption data
      resulted in three scales (Extraversion, Inadequacy, and Religious Orthodoxy)
      showing significant shared environmental influence. Again, effects were most
      substantial for Religious Orthodoxy, where the shared environment accounted for
      nearly 50% of the variance. It is argued that assortative mating cannot explain
      this finding.

PMID- 9523422
TI  - Hydrophobicity and serum sensitivity of Klebsiella pneumoniae treated with sub
      MICs of quinolones.
AB  - Cell surface hydrophobicity and serum sensitivity of Klebsiella pneumoniae, after
      treatment with sub-minimum inhibitory concentrations (sub-MICs) of ciprofloxacin,
      norfloxacin and enoxacin, were studied. The quinolones tested at 1/4, 1/8 and
      1/16 of the MICs decreased surface hydrophobicity. The most significant reduction
      of the bacterial cell surface hydrophobicity was found after treatment with
      antibiotics at 1/16 of the MICs (to 20.3% for both ciprofloxacin and norfloxacin,
      and to 23.6% for enoxacin, compared with control values). The most significant
      increase in the susceptibility of the bacteria to serum bactericidal activity was
      seen after 180 min incubation with ciprofloxacin and enoxacin at 1/16 of their
      MICs. Survival of treated bacteria was 55 +/- 8% 56 +/- 10% as compared with
      controls without antibiotics.

PMID- 9523423
TI  - Antigenic and genetic structure of Borrelia burgdorferi.
AB  - Lyme borreliosis is a disease caused by the spirochaetes Borrelia burgdorferi,
      Borrelia afzelii and Borrelia garinii and it is transmitted by ticks. Most of the
      proteins (outer surface proteins, flagellar proteins and other uncertain location
      proteins) have a strong antigenic variability. Osp A protein genetic and
      serological studies facilitated the differentiation of seven serotypes strongly
      correlated with the known genospecies. The genetic structure of these
      spirochaetes included a large linear chromosome, several linear microchromosomes
      as well as a number of circular plasmids.

PMID- 9523424
TI  - Susceptibility of different isolates of Vibrio harveyi to antibiotics.
AB  - The susceptibility of six Vibrio harveyi strains to antibiotics was studied. Four
      strains originally isolated from diseased penaeids and two reference strains
      originally isolated from either sea water (ATCC 25919) or diseased Talorchestia
      sp. (ATCC 14126) were used in the present study. Results revealed that all three
      strains isolated in Taiwan exhibited resistance against nitrofurantoin,
      novobiocin and sulphonamide. The two reference strains and the strain isolated in
      Indonesia were susceptible to these three antibiotics.

PMID- 9523426
TI  - Cobalt 60 radiation and growth of eleven species of micro-fungi from Evolution
      Canyon, Lower Nahal Oren, Israel.
AB  - Eleven micro-fungal species isolated from both the north facing slope (NFS) and
      the south facing slope (SFS) of Evolution Canyon, Lower Nahal Oren, Israel, were
      examined for growth rates before and after exposure to 60Co irradiation. Species
      of Alternaria, Aspergillus, Humicola, Oidiodendron, and Staphylotrichum from SFS
      grew faster than the NFS isolates while Fusarium, Sordaria, and Stachybotrys grew
      at greater rates from the NFS than from the SFS. Mucor and Ulocladium isolates
      grew at the same rate from both SFS and NFS. The eleven isolates from each slope
      were next subjected to 60Co irradiation. At 40,000 rads exposure, Alternaria,
      Fusarium, and Stachybotrys grew more rapidly when isolated from the NFS, while
      Humicola and Staphylotrichum grew at a faster rate when isolated from the SFS.
      Aspergillus, Mucor, Sordaria, and Ulocladium from both the NFS and the SFS had
      relatively the same growth rate at 40,000 rads exposure. At 400,000 rads
      exposure, growth rates remained much the same for both the N and S exposed
      isolates as they were at 40,000 rads. Above 10(6) rads, growth ceased but
      recovery occurred at various times for individual isolates of the same species
      from opposing canyon slopes.

PMID- 9523425
TI  - Effects of protein kinase C activators and staurosporine on protein kinase
      activity, cell survival, and proliferation in Tetrahymena thermophila.
AB  - Autocrine factors prevent cell death in the ciliate Tetrahymena thermophila, a
      unicellular eukaryote, in a chemically defined medium. At certain growth
      conditions these factors are released at a sufficient concentration by > 500
      cells ml-1 to support cell survival and proliferation. The protein kinase C
      activators phorbol 12-myristate 13-acetate (PMA) or 1-oleyl 2-acetate glycerol
      (OAG) when added to 250 cells ml-1 supported cell survival and proliferation. In
      the presence of the serine and threonine kinase inhibitor staurosporine the cells
      died both at 250 cells ml-1 in cultures supplemented with either PMA or OAG, or
      at 2,500 cells ml-1. At 500 cells ml-1 PMA induced the in vivo phosphorylation of
      at least six proteins. The myelin basic protein fragment 4-14 was phosphorylated
      in vitro in crude extracts of a culture of 250,000 cells ml-1. Both the in vivo
      and the in vitro phosphorylation were inhibited by staurosporine.

PMID- 9523427
TI  - On the slowly rising phase of the sodium gating current in the squid giant axon.
AB  - High-resolution records of the sodium gating current in the squid giant axon
      demonstrate the existence of a slowly rising phase that is first apparent at
      pulse potentials slightly below zero, and becomes increasingly pronounced at more
      positive potentials. At +80 mV the current reaches its peak with a delay of 30
      microseconds at 10 degrees C. It is suggested that this current is generated by
      the first two steps labelled R-->P and P-->A in the S4 units of all four domains
      of the series-parallel gating system, activating the channel before its opening
      by the third steps A-->B in domains I, II and III in conjunction with hydration.
      The kinetics of the slowly rising phase can only be explained by the
      incorporation of an appropriate degree of voltage-dependent cooperativity between
      the S4 voltage-sensors for their two initial transitions.

PMID- 9523428
TI  - Modelling the activation, opening, inactivation and reopening of the voltage
      gated sodium channel.
AB  - A model of the voltage-gated sodium channel is put forward suggesting that the
      four S4 voltage-sensors behave as screw-helices making a series of discrete
      transitions that carry one elementary charge for each notch of the screw helix.
      After the channel has been activated by the first two steps R in equilibrium with
      P in equilibrium with A in all four domains, followed by a voltage-independent
      rearrangement, it is opened by a third cooperative step A in equilibrium with B
      in domains I, II and III in conjunction with hydration. Inactivation is a voltage
      dependent process controlled by the third step A in equilibrium with I in sensor
      IVS4, and the closing of the channel is brought about its dehydration. From the
      inactivated steady state the channel may be reopened by a fourth step, I in
      equilibrium with C in sensor IVS4 and rehydration. The computed kinetics of the
      model are shown to conform closely with those observed experimentally.

PMID- 9523429
TI  - On the origin of skewed distributions of spontaneous synaptic potentials in
      autonomic ganglia.
AB  - The histograms of spontaneous synaptic potentials at synapses in autonomic
      ganglia are described by distributions consisting of mixtures of Gaussians,
      rather than by single Gaussian distributions. The possible origin of these mixed
      distributions is investigated, using Monte-Carlo simulations of the action of
      spontaneously released units of transmitter. A single unit of acetylcholine of
      fixed size, released from an active zone with receptor patches both beneath and
      adjacent to the zone, does not give rise to the observed histograms. But if the
      unit is of variable size, consisting of integer multiples of smaller units, and
      release is from an active zone onto either the receptor patch beneath, or in
      addition onto adjacent patches, then the histogram is well described by a mixture
      of Gaussians. However, this explanation is unlikely to be correct as present
      evidence suggests that in most cases the released unit of transmitter saturates
      the postsynaptic receptor patch beneath the active zone. The final case
      considered is where a unit of transmitter is spontaneously released from an
      active zone, simultaneously with a unit in an adjacent zone less than one micron
      away. The histogram of potentials then conforms to those observed even when there
      are differences in the sizes of the receptor patches. It is suggested that this
      kind of release could provide an explanation for distributions of spontaneous
      potentials that are mixtures of Gaussians.

PMID- 9523430
TI  - Neural networks predict response biases of female tungara frogs.
AB  - Artificial neural networks have become useful tools for probing the origins of
      perceptual biases in the absence of explicit information on underlying neuronal
      substrates. Preceding studies have shown that neural networks selected to
      recognize or discriminate simple patterns may possess emergent biases toward
      pattern size of symmetry--preferences often exhibited by real females--and have
      investigated how these biases shape signal evolution. We asked whether simple
      neural networks could evolve to respond to an actual mate recognition signal, the
      call of the tungara frog, Physalaemus pustulosus. We found that not only were
      networks capable of recognizing the call of the tungara frog, but that they made
      remarkably accurate quantitative predictions about how well females generalized
      to many novel calls, and that these predictions were stable over several
      architectures. The data suggest that the degree to which P. pustulosus females
      respond to a call may often be an incidental by-product of a sensory system
      selected simply for species recognition.

PMID- 9523431
TI  - The function of Barbary macaque copulation calls.
AB  - In a wide variety of animal species, females produce vocalizations specific to
      mating contexts. It has been proposed that these copulation calls function to
      incite males to compete for access to the calling female. Two separate advantages
      of inciting male-male competition in this way have been put forward. The first
      suggests that as a result of calling, females are only mated by the highest
      ranking male in the vicinity (indirect mate choice hypothesis). The second
      proposes that copulation calling results in a female being mated by many males,
      thus promoting competition at the level of sperm (sperm competition hypothesis).
      In this paper, I give results from the first experimental study to test these
      hypotheses. Playback was used to examine the function of copulation calls of
      female Barbary macaques (Macaca sylvanus) in Gibraltar. Although rank did not
      affect lone males' likelihood of approaching copulation calls, when playbacks
      were given to pairs of males only the higher ranking individual approached.
      Moreover, females were mated significantly sooner after playback of their
      copulation call than after playback of a control stimulus. These results suggest
      that the copulation calls of female Barbary macaques play a key role in affecting
      patterns of male reproductive behaviour, not only providing an indirect mechanism
      of female choice, but also promoting sperm competition by reducing the interval
      between copulations. Potential fitness benefits of inciting male-male competition
      at these two levels are discussed.

PMID- 9523432
TI  - Genetic diversity in Leavenworthia populations with different inbreeding levels.
AB  - Levels of neutral genetic diversity within and between populations were compared
      between outcrossing (self-incompatible) and inbreeding populations in the annual
      plant genus Leavenworthia. Two taxonomically independent comparisons are
      possible, since self-incompatibility has been lost twice in the group of species
      studied. Within inbred populations of L.uniflora and L.crassa, no DNA sequence
      variants were seen among the alleles sampled, but high diversity was seen in
      alleles from populations of the outcrosser L. stylosa, and in self-incompatible
      L. crassa populations. Diversity between populations was seen in all species.
      Although total diversity values were lower in the sets of inbreeding populations,
      between-population values were as high or higher, than those in the outcrossing
      taxa. Possible reasons for these diversity patterns are discussed. As the effect
      of inbreeding appears to be a greater than twofold reduction in diversity, we
      argue that some process such as selection for advantageous mutations, or against
      deleterious mutations, or bottlenecks occurring predominantly in the inbreeders,
      appears necessary to account for the findings. If selection for advantageous
      mutations is responsible, it appears that it must be some form of local adaptive
      selection, rather than substitution of alleles that are advantageous throughout
      the species. This is consistent with the finding of high between-population
      diversity in the inbreeding taxa.

PMID- 9523433
TI  - Molecular genetic evidence for parallel evolution in a marine gastropod,
      Littorina subrotundata.
AB  - Littorina subrotundata from wave-exposed rocky shores differ consistently in
      shell and radula morphology from those found in wave-protected salt-marshes. To
      determine if the two morphological forms of this gastropod represent separate
      species, clades, or ecotypes, DNA sequencing and single-stranded conformational
      polymorphism (SSCP) analysis were used to assay variation in a 480 bp fragment of
      the mitochondrial cytochrome-b gene. Several nested analyses of molecular
      variance (AMOVA) were then performed to test if grouping populations by
      geographical region or habitat type better explained the distribution of
      cytochrome-b haplotypes among some northeastern Pacific populations. The analysis
      by geographic region resulted in a significant variance component that explained
      53% of the variance, whereas the analysis by habitat type was not significant.
      These results, along with previous studies showing that the differences in shell
      morphology among different forms have a heritable component, suggest that the two
      forms are ecotypes and not separate species or clades as had been previously
      proposed. These results also imply that each ecotype has evolved independently in
      each geographic area and that the morphological similarity of individuals from
      the same habitat type is most likely the result of parallel evolution.

PMID- 9523434
TI  - Coevolution of recovery ability and virulence.
AB  - Most models for coevolution of hosts and parasites are based on the assumption
      that resistance of hosts to parasites is an all-or-nothing effect. In many cases,
      for example where parasites require an appropriate receptor on host cells, this
      is a reasonable assumption. However, in many other cases, for example where hosts
      mount an immune response, this picture may be too simple. An immune system is
      expensive to maintain, which poses a question as to how much of its resources a
      host should allocate to resist parasites: if the risk of infection is low,
      natural selection may favour hosts with less effective immune systems. As optimal
      allocation to defence will depend on the force of infection, and the force of
      infection, in turn, depends on the level of defence in the rest of the host
      population, a game-theoretic approach is necessary. Here I analyse a simple model
      for the evolution of the ability to recover from infection. If parasites are not
      allowed to coevolve, the outcome is a single evolutionarily stable strategy
      (ESS). If the parasites coevolve, multiple evolutionary outcomes are possible,
      one in which the parasites are relatively avirulent and common and the hosts
      invest little in recovery ability, and another (the escalated arms race) where
      parasites are rare but virulent and the hosts invest heavily in defence.

PMID- 9523435
TI  - Population dynamics of Norwegian red deer: density-dependence and climatic
      variation.
AB  - We present a model on plant-deer climate interactions developed for improving our
      understanding of the temporal dynamics of deer abundance and, in particular, how
      intrinsic (density-dependent) and extrinsic (plants, climate) factors influence
      these dynamics. The model was tested statistically by analysing the dynamics of
      five Norwegian red deer populations between 1964 and 1993. Direct and delayed
      density-dependence significantly influenced the development of the populations:
      delayed density-dependence primarily operated through female density, whereas
      direct density-dependence acted through both female and male densities.
      Furthermore, population dynamics of Norwegian red deer were significantly
      affected by climate (as measured by the global weather phenomenon, the North
      Atlantic Oscillation: NAO). Warm, snowy winters (high NAO) were associated with
      decreased deer abundance, whereas the delayed (two-year) effect of warm, snowy
      winters had a positive effect on deer abundance. Our analyses are argued to have
      profound implications for the general understanding of climate change and
      terrestrial ecosystem functioning.

PMID- 9523436
TI  - Receptor noise as a determinant of colour thresholds.
AB  - Inferences about mechanisms at one particular stage of a visual pathway may be
      made from psychophysical thresholds only if the noise at the stage in question
      dominates that in the others. Spectral sensitivities, measured under bright
      conditions, for di-, tri-, and tetrachromatic eyes from a range of animals can be
      modelled by assuming that thresholds are set by colour opponency mechanisms whose
      performance is limited by photoreceptor noise, the achromatic signal being
      disregarded. Noise in the opponency channels themselves is therefore not
      statistically independent, and it is not possible to infer anything more about
      the channels from psychophysical thresholds. As well as giving insight into
      mechanisms of vision, the model predicts the performance of colour vision in
      animals where physiological and anatomical data on the eye are available, but
      there are no direct measurements of perceptual thresholds. The model, therefore,
      is widely applicable to comparative studies of eye design and visual ecology.

PMID- 9523437
TI  - Independent component filters of natural images compared with simple cells in
      primary visual cortex.
AB  - Properties of the receptive fields of simple cells in macaque cortex were
      compared with properties of independent component filters generated by
      independent component analysis (ICA) on a large set of natural images. Histograms
      of spatial frequency bandwidth, orientation tuning bandwidth, aspect ratio and
      length of the receptive fields match well. This indicates that simple cells are
      well tuned to the expected statistics of natural stimuli. There is no match,
      however, in calculated and measured distributions for the peak of the spatial
      frequency response: the filters produced by ICA do not vary their spatial scale
      as much as simple cells do, but are fixed to scales close to the finest ones
      allowed by the sampling lattice. Possible ways to resolve this discrepancy are
      discussed.

PMID- 9523438
TI  - Overcoming cytoplasmic incompatibility in Drosophila.
AB  - The endocellular microbe Wolbachia pipientis infects a wide variety of
      invertebrate species, in which its presence is closely linked to a form of
      reproductive failure termed cytoplasmic incompatibility (CI). CI renders infected
      males unable to father offspring when mated to uninfected females. Because CI can
      dramatically affect fitness in natural populations, mechanisms that abate CI can
      have equally large impacts on fitness. We have discovered that repeated
      copulation by Wolbachia-infected male Drosophila simulans significantly
      diminishes CI. Repeated copulation does not prevent Wolbachia from populating
      developing spermatids, but may reduce the time during spermatogenesis when
      Wolbachia can express CI. This restoration of fertility in premated infected
      males could have important implications for Wolbachia transmission and
      persistence in nature and for its exploitation as an agent of biological pest
      control.

PMID- 9523439
TI  - Isolation and characterization of a cDNA encoding a potential morphogen from the
      marine sponge Geodia cydonium that is conserved in higher metazoans.
AB  - Species belonging to the lowest metazoan phylum, the sponges (Porifera), exhibit
      a surprisingly complex and multifaceted Bauplan (body plan). Recently, key
      molecules have been isolated from sponges which demonstrate that the cells of
      these animals are provided with characteristic metazoan adhesion and signal
      transduction molecules, allowing tissue formation. In order to understand which
      factors control the spatial organization of these cells in the sponge body plan,
      we screened for a cDNA encoding a soluble modulator of the behaviour of
      endothelial cells. A cDNA encoding a putative protein, which is highly similar to
      the human and mouse endothelial monocyte-activating polypeptide (EMAP) II has
      been isolated from a library of the marine sponge Geodia cydonium. The sponge
      EMAP-related polypeptide (EMAPR) has been termed EMAPR1_GC. The full-length cDNA
      clone, GCEMAPR1, has a size of 592 nucleotides (nt) and contains a 447 nt-long
      potential open reading frame; the molecular weight (MW) of the deduced amino acid
      sequence, 16,499 Da, is close to that of mature mammalian EMAP II (ca. 18 kDa).
      The sponge polypeptide is also closely related to a deduced polypeptide from the
      cosmid clone F58B3 isolated from Caenorhabditis elegans. A phylogenetic analysis
      revealed that the sponge and the nematode EMAPR molecules form a cluster which is
      significantly separated from the corresponding mammalian EMAP molecules. The
      function of the first cloned putative soluble modulator of endothelial cells in
      sponges remains to be determined.

PMID- 9523440
TI  - Mechanics of blood supply to the heart: wave reflection effects in a right
      coronary artery.
AB  - Mechanics of blood flow in the coronary circulation have in the past been based
      largely on models in which the detailed architecture of the coronary network is
      not included because of lack of data: properties of individual vessels do not
      appear individually in the model but are represented collectively by the elements
      of a single electric circuit. Recent data from the human heart make it possible,
      for the first time, to examine the dynamics of flow in the coronary network based
      on detailed, measured vascular architecture. In particular, admittance values
      along the full course of the right coronary artery are computed based on actual
      lengths and diameters of the many thousands of branches which make up the
      distribution system of this vessel. The results indicate that effects of wave
      reflections on this flow are far more significant than those generally suspected
      to occur in coronary blood flow and that they are actually the reverse of the
      well known wave reflection effects in the aorta.

PMID- 9523441
TI  - Characterizing dose-response: I: Critical assessment of the benchmark dose
      concept.
AB  - We present a critical assessment of the benchmark dose (BMD) method introduced by
      Crump as an alternative method for setting a characteristic dose level for
      toxicant risk assessment. The no-observed-adverse-effect-level (NOAEL) method has
      been criticized because it does not use all of the data and because the
      characteristic dose level obtained depends on the dose levels and the statistical
      precision (sample sizes) of the study design. Defining the BMD in terms of a
      confidence bound on a point estimate results in a characteristic dose that also
      varies with the statistical precision and still depends on the study dose levels.
      Indiscriminate choice of benchmark response level may result in a BMD that
      reflects little about the dose-response behavior available from using all of the
      data. Another concern is that the definition of the BMD for the quantal response
      case is different for the continuous response case. Specifically, defining the
      BMD for continuous data using a ratio of increased effect divided by the
      background response results in an arbitrary dependence on the natural background
      for the endpoint being studied, making comparison among endpoints less meaningful
      and standards more arbitrary. We define a modified benchmark dose as a point
      estimate using the ratio of increased effect divided by the full adverse response
      range which enables consistent placement of the benchmark response level and
      provides a BMD with a more consistent relationship to the dose-response curve
      shape.

PMID- 9523442
TI  - Lognormal distributions for skin area as a function of body weight.
AB  - This paper reanalyzes the dataset cited by the U.S. Environmental Protection
      Agency in its Exposure Factors Handbook that contains measurements of skin area,
      height, and body weight for 401 people spanning all stages of development. The
      reanalysis shows that a univariate model for total skin area as a function of
      body weight gives useful and practical results with little or no loss of
      reliability as compared to the Agency's bivariate model. This new result leads to
      a new method to develop Lognormal distributions for total skin area as a function
      of body weight alone.

PMID- 9523443
TI  - Quantifying the distribution of inhalation exposure in human populations: 2.
      Distributions of time spent by adults, adolescents, and children at home, at
      work, and at school.
AB  - Using distributions of time spent at various ventilation levels, ranges of
      inhalation exposure in the population can be established. Distributions of
      exposure time were determined using results of a study by the California Air
      Resources Board (CARB) which focused on time spent by humans participating in
      various activities and the locations where the activities occurred. The daily at
      home activities from the CARB study were assigned to one of three ventilation
      levels, generating aggregate time periods. Distinct age and gender populations
      were identified, and distributions for aggregate time were established for these
      populations at each of the ventilation levels. In addition to aggregate time
      spent at home, distributions for various ages and genders were established for
      aggregate time spent at school and work. By combining distributions of aggregate
      time with corresponding ventilation rates, the distribution of inhalation rates
      can be established for at home, at work, and at school exposures.

PMID- 9523444
TI  - The EPA health risk assessment of methylcyclopentadienyl manganese tricarbonyl
      (MMT).
AB  - This paper describes the U.S. Environmental Protection Agency's assessment of
      potential health risks associated with the possible widespread use of a manganese
      (Mn)-based fuel additive, methylcyclopentadienyl manganese tricarbonyl (MMT).
      This assessment was significant in several respects and may be instructive in
      identifying certain methodological issues of general relevance to risk
      assessment. A major feature of the inhalation health risk assessment was the
      derivation of Mn inhalation reference concentration (RfC) estimates using various
      statistical approaches, including benchmark dose and Bayesian analyses. The
      exposure assessment component used data from the Particle Total Exposure
      Assessment Methodology (PTEAM) study and other sources to estimate personal
      exposure levels of particulate Mn attributable to the permitted use of MMT in
      leaded gasoline in Riverside, CA, at the time of the PTEAM study; on this basis
      it was then possible to predict a distribution of possible future exposure levels
      associated with the use of MMT in all unleaded gasoline. Qualitative as well as
      quantitative aspects of the risk characterization are summarized, along with
      inherent uncertainties due to data limitations.

PMID- 9523445
TI  - Air nicotine and saliva cotinine as indicators of workplace passive smoking
      exposure and risk.
AB  - We model nicotine from environmental tobacco smoke (ETS) in office air and
      salivary cotinine in nonsmoking U.S. workers. We estimate that: an average
      salivary cotinine level of 0.4 ng/ml corresponds to an increased lifetime
      mortality risk of 1/1000 for lung cancer, and 1/100 for heart disease; > 95% of
      ETS-exposed office workers exceed OSHA's significant risk level for heart disease
      mortality, and 60% exceed significant risk for lung cancer mortality; 4000 heart
      disease deaths and 400 lung cancer deaths occur annually among office workers
      from passive smoking in the workplace, at the current 28% prevalence of
      unrestricted smoking in the office workplace.

PMID- 9523446
TI  - Worry and risk perception.
AB  - Risk perception is sometimes measured by means of judgments about worry,
      sometimes as perceived risk more directly. However, perceived level of risk calls
      for a more intellectual judgment and worry tends to refer to emotional reactions.
      These two are therefore not the same and need not be strongly correlated. Results
      reported here show that perceived risk and worry are indeed weakly correlated,
      both for generalized worry and for more specific measures of worry matched with
      the same hazard as risk ratings. A distinction is suggested between cognitive,
      abstract hazards and concrete, sensory hazards, with implications for the worry
      perceived risk relationship. It was furthermore found by means of cluster
      analysis that there were groups of subject displaying different dynamics of risk
      and worry.

PMID- 9523447
TI  - Methodological approaches to assessing risk perceptions associated with food
      related hazards.
AB  - The psychometric approach developed by Slovic and his co-workers has been
      effectively used to assess risk perceptions associated with different food
      related hazards. However, further examination (using questionnaire data and
      partial correlation techniques) has indicated that technological hazards are
      highly differentiated from lifestyle hazards, in terms of both hazard control and
      knowledge about the hazard. Optimistic bias was also seen to vary between
      hazards. Further research has focused on a particular hazard, genetic
      engineering. Risk perceptions associated with genetic engineering are underpinned
      by ethical concern and questions relating to perceived need for the technology,
      as well as perceptions of risk or harm. However, increasing the specificity of
      hazard stimuli was found to alter the factor structure of underlying risk
      perceptions. The utility of preference mapping procedures in determining
      individual differences in trust in risk regulators is also discussed.

PMID- 9523448
TI  - Risk perceptions of offshore workers on UK oil and gas platforms.
AB  - Knowledge of the workforce's risk perceptions and attitudes to safety is
      necessary for the development of a safety culture, where each person accepts
      responsibility for working safely. The ACSNI Human Factors report stresses the
      importance of assessing workforce perceptions of risk to achieve a proper safety
      culture. Risk perception research has been criticized for insufficient analysis
      of the causal relationships between risk factors and perceived risk. The present
      study reports some of the factors which predicted risk perception in a sample of
      622 employees from six UKCS offshore oil installations who completed a 15-section
      questionnaire. This paper focuses on the accuracy of workers' risk perceptions
      and what underlying factors predict the perception of personal risk from both
      major and minor hazards.

PMID- 9523449
TI  - Risk perception by offshore oil personnel during bad weather conditions.
AB  - This article presents the results of analyses of employee subjective risk
      assessments caused by platform movements on an offshore oil installation in the
      Norwegian sector of the North Sea. The results are based on a self-completion
      questionnaire survey conducted among 179 respondents covering three shifts on the
      platform. The data collection was carried out during the spring of 1994. A
      minority expressed worry due to platform movements. A greater proportion of the
      personnel stated worry about the construction of the platform. The personnel were
      more unsafe when they assessed their own safety attitudes with regard to specific
      potentially hazardous consequences of platform movements. Two approaches aimed at
      modeling worry and concern caused by platform movements were tested. The models
      were the mental imagery approach and the rationalistic approach. The
      rationalistic and mental imagery models fitted equally well. Implications of the
      results for risk communication are discussed.

PMID- 9523450
TI  - Judgments of personal and environmental risks of consumer products--do they
      differ?
AB  - Many psychometric studies have investigated judgments concerning personal risks
      from technologies, activities or consumer products, but only a few studies have
      included judgments of risk to the environment. Thus, little is known about this
      aspect of environmental risk perception, and whether it differs from personal
      risk perception. This study investigates risk judgments for 30 consumer products
      of various types such as herbal remedies, mobile telephones, genetically
      engineered drugs, or garden pesticides. A survey was conducted in two German
      cities: Leipzig and West Berlin. In total, 408 subjects evaluated the consumer
      products with regard to personal and environmental risk (and other risk-related
      aspects) and whether they would recommend the product to others. The findings
      show statistically significant differences between the mean values of perceived
      personal risk and environmental risk for most products. Despite these
      differences, the rank order of mean personal risk and environmental risk
      judgments for the products is quite similar. However, separate analyses for each
      product reveal that correlations between perceived personal and environmental
      risk vary strongly across products. Multiple regression analyses with personal
      and environmental risk judgments as predictors and product recommendation as
      criterion, run separately for each consumer product, show that it is mainly the
      judgment of perceived personal risk that explains product recommendation.
      Perceived risk to the environment adds little explanatory power. The study also
      explores differences in judgments of personal and environmental risk with regard
      to two sociodemographic variables: location (former East Germany vs. West
      Germany) and gender. Differences in both types of risk judgments are found with
      regard to location but not for gender.

PMID- 9523451
TI  - Enhancement of the biodegradability of model wastewater containing recalcitrant
      or inhibitory chemical compounds by photocatalytic pre-oxidation.
AB  - m-Dinitrobenzene, diphenylamine and resorcinol, three aromatic compounds found
      inhibitory or recalcitrant to biological treatments, were chosen as model
      chemicals for this study on the integration of photocatalytic-biological
      treatments. The degradation of each of these compounds was achieved by
      ultraviolet photocatalytic oxidation, leading to the formation of intermediate
      compounds. The photocatalytic treatment was performed in a TiO2 slurry reactor
      containing an aqueous solution of one of the three chemicals. The
      biodegradability of model wastewater treated photocatalytically was measured in
      terms of BOD1/TOC. Intermediate compounds that appeared at early stages of the
      photocatalytic degradation of m-dinitrobenzene or diphenylamine seemed to be more
      inhibitory than the parent compounds but this was not the case for resorcinol. A
      substantial improvement in BOD1/TOC could be achieved, but it required the
      mineralization of at least 80% of the organic carbon originally in the water.
      Microtox toxicity results confirmed the BOD1/TOC trends for diphenylamine.

PMID- 9523452
TI  - Implementation of natural attenuation at a JP-4 jet fuel release after active
      remediation.
AB  - After eighteen months of active remediation at a JP-4 jet-fuel spill, a residual
      of unremediated hydrocarbon remained. Further site characterization was conducted
      to evaluate the contribution of natural attenuation to control exposure to
      hazards associated with the residual contamination in the subsurface. Activities
      included the detailed characterization of ground-water flow through the spill;
      the distribution of fuel contaminants in groundwater; and the analysis of soluble
      electron acceptors moving into the spill from upgradient. These activities
      allowed a rigorous evaluation of the transport of contaminants from the spill to
      the receptor of groundwater, the Pasquotank River. The transport of dissolved
      contaminants of concern, that is benzene, toluene, ethyl benzene, xylene isomers
      (BTEX) and methyl-tertiary-butyl ether (MTBE), into the river from the source
      area was controlled by equilibrium dissolution from the fuel spill to the
      adjacent groundwater, diffusion in groundwater from the spill to permeable layers
      in the aquifer, and advective transport in the permeable layers. The estimated
      yearly loading of BTEX compounds and MTBE into the receptor was trivial even
      without considering biological degradation. The biodegradation of hydrocarbon
      dissolved in groundwater through aerobic respiration, denitrification, sulfate
      reduction, and iron reduction was estimated from changes in ground-water
      chemistry along the flow path. The concentrations of target components in
      permanent monitoring wells continue to decline over time. Long term monitoring
      will ensure that the plume is under control, and no further active remediation is
      required.

PMID- 9523453
TI  - Genes for all metals--a bacterial view of the periodic table. The 1996 Thom Award
      Lecture.
AB  - Bacterial chromosomes have genes for transport proteins for inorganic nutrient
      cations and oxyanions, such as NH4+, K+, Mg2+, Co2+, Fe3+, Mn2+, Zn2+ and other
      trace cations, and PO4(3-), SO4(2-) and less abundant oxyanions. Together these
      account for perhaps a few hundred genes in many bacteria. Bacterial plasmids
      encode resistance systems for toxic metal and metalloid ions including Ag+, AsO2
      , AsO4(3-), Cd2+, Co2+, CrO4(2-), Cu2+, Hg2+, Ni2+, Pb2+, TeO3(2-), Tl+ and Zn2+.
      Most resistance systems function by energy-dependent efflux of toxic ions. A few
      involve enzymatic (mostly redox) transformations. Some of the efflux resistance
      systems are ATPases and others are chemiosmotic ion/proton exchangers. The Cd(2+)
      resistance cation pump of Gram-positive bacteria is membrane P-type ATPase, which
      has been labeled with 32P from [gamma-32P]ATP and drives ATP-dependent Cd2+ (and
      Zn2+) transport by membrane vesicles. The genes defective in the human hereditary
      diseases of copper metabolism, Menkes syndrome and Wilson's disease, encode P
      type ATPases that are similar to bacterial cadmium ATPases. The arsenic
      resistance system transports arsenite [As(III)], alternatively with the ArsB
      polypeptide functioning as a chemiosmotic efflux transporter or with two
      polypeptides, ArsB and ArsA, functioning as an ATPase. The third protein of the
      arsenic resistance system is an enzyme that reduces intracellular arsenate
      [As(V)] to arsenite [As(III)], the substrate of the efflux system. In Gram
      negative cells, a three polypeptide complex functions as a chemiosmotic
      cation/protein exchanger to efflux Cd2+, Zn2+ and Co2+. This pump consists of an
      inner membrane (CzcA), an outer membrane (CzcC) and a membrane-spanning (CzcB)
      protein that function together.

PMID- 9523454
TI  - Biodegradation of cyanides, cyanates and thiocyanates to ammonia and carbon
      dioxide by immobilized cells of Pseudomonas putida.
AB  - Pseudomonas putida utilizes cyanide as the sole source of carbon and nitrogen.
      Agar, alginate, and carrageenan were screened as the encapsulating matrices for
      P. putida. Alginate-immobilized cells of P. putida degraded sodium cyanide (NaCN)
      more efficiently than non-immobilized cells or cells immobilized in agar or
      carrageenan. The end products of biodegradation of cyanide were identified as
      ammonia (NH3) and carbon dioxide (CO2). These products changed the medium pH. In
      bioreactors, the rate of cyanide degradation increased with an increase in the
      rate of aeration. Maximum utilization of cyanide was observed at 200 ml min-1 of
      aeration. Immobilized cells of P. putida degraded cyanides, cyanates and
      thiocyanates to NH3 and CO2. Use of Na[14C]-CN showed that 70% of carbon of
      Na[14C]-CN was converted into 14CO2 and only 10% was associated with the cell
      biomass. The substrate-dependent kinetics indicated that the Km and Vmax values
      of P. putida for the substrate, NaCN were 14 mM and 29 nmol of oxygen consumed mg
      protein-1 min-1 respectively.

PMID- 9523455
TI  - Production of pectinesterase and polygalacturonase by Aspergillus niger in
      submerged and solid state systems.
AB  - Production of pectinesterase and polygalacturonase by Aspergillus niger was
      studied in submerged and solid-state fermentation systems. With pectin as a sole
      carbon source, pectinesterase and polygalacturonase production were four and six
      times higher respectively in a solid state system than in a submerged
      fermentation system and required a shorter time for enzyme production. The
      addition of glucose increased pectinesterase and polygalacturonase production in
      the solid state system but in submerged fermentation the production was markedly
      inhibited. A comparison of enzyme productivities showed that those determined for
      pectinesterase and polygalacturonase with pectin as a carbon source were three
      and five times higher by using the solid state rather than the submerged
      fermentation system. The productivities of the two enzymes were affected by
      glucose in both fermentation systems. The membranes of cells from the solid state
      fermentation showed increased levels of C18:1, C16:0 and C18:0 fatty acids.
      Differences in the regulation of enzyme synthesis by Aspergillus niger depended
      on the fermentation system, favoring the solid state over the submerged
      fermentation for pectinase production.

PMID- 9523456
TI  - Mycotoxins of Alternaria alternata produced on ceiling tiles.
AB  - The production of mycotoxins by Alternaria alternata in cellulosic ceiling tiles
      was examined with thin-layer chromatography and high-performance liquid
      chromatography procedures. Alternariol and alternariol monomethyl ether were
      found in ceiling tile extracts, whereas extracts of control rice cultures of all
      three isolates produced these mycotoxins plus altenuene and altertoxin I.
      Extensive fungal growth and mycotoxin production occurred in the ceiling tiles at
      relative humidities of 84-89% and 97%.

PMID- 9523457
TI  - Effect of the siderophore alcaligin E on the bioavailability of Cd to Alcaligenes
      eutrophus CH34.
AB  - Alcaligin E, the siderophore of the heavy metal-resistant A. eutrophus strain
      CH34, was shown to interact with Cd and consequently affect its bioavailability
      and toxicity. The addition of alcaligin E markedly stimulated the growth in the
      presence of Cd of an alcaligin E-deficient CH34 derivative. Using bioluminescence
      assays, this effect could be assigned to a decrease in bioavailability of Cd in
      the presence of alcaligin E. However, Cd-uptake studies showed no influence of
      alcaligin E on the cellular concentration of Cd. Furthermore, by scanning
      electron microscopy, the morphology of precipitated Cd crystals was shown to be
      altered by alcaligin E. These data suggest that alcaligin E, besides its function
      in iron supply to the cell, provides a protection against heavy metal toxicity. A
      link between the A. eutrophus CH34 siderophore system and the czc-mediated Cd
      efflux system is hypothesized.

PMID- 9523458
TI  - Room temperature sterilization of surfaces and fabrics with a one atmosphere
      uniform glow discharge plasma.
AB  - We report the results of an interdisciplinary collaboration formed to assess the
      sterilizing capabilities of the One Atmosphere Uniform Glow Discharge Plasma
      (OAUGDP). This newly-invented source of glow discharge plasma (the fourth state
      of matter) is capable of operating at atmospheric pressure in air and other
      gases, and of providing antimicrobial active species to surfaces and workpieces
      at room temperature as judged by viable plate counts. OAUGDP exposures have
      reduced log numbers of bacteria, Staphylococcus aureus and Escherichia coli, and
      endospores from Bacillus stearothermophilus and Bacillus subtilis on seeded solid
      surfaces, fabrics, filter paper, and powdered culture media at room temperature.
      Initial experimental data showed a two-log10 CFU reduction of bacteria when 2 x
      10(2) cells were seeded on filter paper. Results showed > or = 3 log10 CFU
      reduction when polypropylene samples seeded with E. coli (5 x 10(4)) were
      exposed, while a 30 s exposure time was required for similar killing with S.
      aureus-seeded polypropylene samples. The exposure times required to effect > or =
      6 log10 CFU reduction of E. coli and S. aureus on polypropylene samples were no
      longer than 30 s. Experiments with seeded samples in sealed commercial
      sterilization bags showed little or no differences in exposure times compared to
      unwrapped samples. Plasma exposure times of less than 5 min generated > or = 5
      log10 CFU reduction of commercially prepared Bacillus subtilis spores (1 x
      10(5)); 7 min OAUGDP exposures were required to generate a > or = 3 log10 CFU
      reduction for Bacillus stearothermophilus spores. For all microorganisms tested,
      a biphasic curve was generated when the number of survivors vs time was plotted
      in dose-response cures. Several proposed mechanisms of killing at room
      temperature by the OAUGDP are discussed.

PMID- 9523460
TI  - Imaging techniques in the analysis of brain function and behaviour.
AB  - Techniques such as positron-emission tomography, single-photon-emission computed
      tomography, functional magnetic-resonance imaging and magnetoencephalography
      permit the observation of biological processes in the brain in a noninvasive
      manner. They have yielded new insights into the biological interrelations of
      sensory, motor and cognitive functions, as well as into brain diseases. Combined
      use of these techniques may provide more information than just the sum of its
      constituents, and this may narrow the gap between the biological data provided by
      these techniques and the mental models described by clinicians, mathematicians,
      psychologists and philosophers.

PMID- 9523459
TI  - Epoxide hydrolases: new tools for the synthesis of fine organic chemicals.
AB  - Epoxide hydrolases are ubiquitous enzymes able to hydrolyse an epoxide to its
      corresponding vicinal diol. These hydrolases have been shown often to be highly
      enantio- and regioselective, thus allowing both the epoxide and the diol to be
      prepared at high enantiomeric purity. Because these products show high chemical
      versatility, they are important for the synthesis of various biologically active
      products. Recent studies have provided valuable information on the molecular
      structure of these enzymes, as well as insight to the enzymatic mechanisms
      involved.

PMID- 9523461
TI  - Fluorescent-protein biosensors: new tools for drug discovery.
AB  - Recent improvements in target discovery and high-throughput screening have
      increased the pressure at key points along the drug-discovery pipeline. High
      content screening was developed to ease the bottlenecks formed at the target
      validation and lead-optimization points, and a new generation of reagents that
      report on specific molecular processes in living cells (fluorescent-protein
      biosensors) have been important in its development. Creative designs of
      fluorescent-protein biosensors have emerged and been used to measure the
      molecular dynamics of macromolecules, metabolites and ions. Recent applications
      of fluorescent-protein biosensors to biological problems have provided a
      foundation for their use in biotechnology.

PMID- 9523462
TI  - [Primary extragonadal germ cell tumors].
AB  - Extragonadal germ cell tumors (ECT) account for only 2-5% of all germ cell
      neoplasms in adults. These tumors in part biologically distinct from their
      testicular counterparts and have distinct clinical features. The author presents
      a review of articles in the literature about hematologic neoplasia associated
      with mediastinal germ cell tumors. These hematologic neoplasms are not related to
      therapy. The optimal management ECT continues to be defined.

PMID- 9523463
TI  - [Occurrence and susceptibility of hospital strains producing enzymes with a wide
      spectrum of substrate profiles].
AB  - In connection with more and more frequent occurrence of extended spectrum beta
      lactamases an effort has been made to detect their presence in the biological
      materials coming from the patients of different wards of Mining Hospital in
      Sosnowiec from January to September 1995. Among 38 diagnostic materials, from
      which the strains in question were isolated, the following materials have been
      examined: bronchial lavage (52.6%), surgical wounds (18.4%), urines (15.8%) and
      others (13.2%). The examined diagnostic materials came from Intensive Care Unit
      (87.0%), Casualty and Orthopaedic Surgery Clinic (5.0%) and General Surgery
      Clinic (3.0%). The most frequently isolated microorganisms were Klebsiella
      pneumoniae. (47.4%), Serratia marcescens (36.8%), Enterobacter cloacae (10.5%)
      and others (5.3%). Half of the examined strains constituted those producing
      extended spectrum beta-lactamases and probably possessing an extra resistance
      mechanism: (Serratia marcescens--74%, Enterobacter cloacae--21%, Enterobacter
      aerogenes--5.0%) and 50% were those producing extended--spectrum beta-lactamases.
      (Klebsiella pneumoniae--95%, Escherichia coli--5%). Susceptibility of the
      examined strains to anti-microbial antibiotics was diverse. Full susceptibility
      of the analysed strains has been observed exclusively in case of Karbapenems
      (Imipenem, Meropenem and Cefamycyn). In case of beta-lactamase with beta
      lactamase inhibitor combinations susceptibility was diverse and dependent on the
      species of the examined microorganism.

PMID- 9523464
TI  - [Fibrinolysis process in blood of patients with bladder carcinoma].
AB  - In patients with bladder carcinoma a shorter ELT, and increased concentrations of
      EDP and t-PA were observed. These indicate on fibrinolysis activation caused by
      the released of t-PA. The increased fibrinolytic activity can be a cause of
      hemorrhagic complication occurring sometimes in bladder carcinoma. We observed
      much stronger activation of fibrinolysis in patients with an advanced bladder
      carcinoma.

PMID- 9523465
TI  - [Evaluation of long-term results of surgical treatment of lung cancer].
AB  - In term Jan. 1988 and Dec. 1989 222 patients from 31 to 77 years old were
      surgically treated for lung cancer at The Department of The Thoracic Surgery of
      Medical Academy in Bydgoszcz. 102 patients (45.9%) had the first stage of
      disease, 31(13.9%) second and 89(40.2%) third stage of disease. 179(80.8%)
      patients had a resected proceeder and 43(19.2%) explorative thoracotomy. The
      perioperative mortality was 13(5.8%) patients. 64(36.4%) patients survived 5
      years. We found a significant influence of a stage and the range of a surgical
      resection on the long-term survival. We found that 5-years survivals did not
      depend on the age and sex and place of life of the patients and histological type
      of cancer.

PMID- 9523466
TI  - [Use of long-acting drainage (sino-ject) in treatment of chronic maxillary
      sinusitis].
AB  - The authors present the results of treatment of chronic maxillary sinusitis with
      punctures and with permanent drainage (sino-ject). The use of permanent drainage
      shortened the time of treatment and increased percentage of very good results of
      treatment. Presented method of permanent drainage of maxillary sinus avoid many
      punctures of sinus. The drainage of sinus allow for each day rinsing of sinus
      with physiological saline and with drugs (mucolitic, antibiotic) and also for
      bacteriological examination of sinus secretion. As in classical puncture of
      maxillary sinus the permanent drainage play a diagnostic and therapeutic roles.
      The permanent drainage of maxillary sinus allow for inflow of oxygen into sinus
      and protect from anaerobic infection. The fact that puncture needle is pushed to
      a depth of only 1 cm greatly reduces the risk of injuring neighbouring
      structures. This method enables puncture of maxillary sinus with minimum trauma
      and hardly any pain.

PMID- 9523467
TI  - [Mediastinal abscesses and empyema of the pleural cavity after iatrogenic
      fracture of the sternum].
AB  - A case report presents fracture of sternum during the resuscitation and in
      continuity iatrogenic hematoma and afterwards abscessus of mediastinum, and
      empyema the both of pleura cavities. Fracture of thorax wall is rather often
      event, but in the most, it has not adverse effects. This case refers to 68 years
      old patient, who had one of the most serious complications: abscessus of
      mediastinum, empyema of left and right pleura cavities with perforation outside
      the anterior wall of thorax. He was treated in General Hospital Biala Podlaska,
      Department of Surgery with good results and was extracted home as well-being
      patient after 35 days spent in hospital the second hospitalisation.

PMID- 9523468
TI  - [Ischemic hepatitis].
AB  - The patients with chronic congestive heart failure and acute deterioration of
      heart failure (pulmonary oedema, significant reduction of blood pressure) have
      decrease liver's perfusion with signs of acute damage of liver's cells--ischemic
      hepatitis. Aspat, AIAT and LDH in blood rich very high level. The level of
      bilirubin, alkaline phosphatase and glucose increase slightly. Hepatotoxic
      viruses are never observed. The authors described a case of 34 years old man, who
      two years earlier had large myocardial infarction with aneurysm of heart and
      congestive heart failure. He was admitted to hospital in shock. The shock was
      caused probably by overdose of nitroglycerin. In ECG and Echo examinations he had
      no signs of acute myocardial infarction, but we observed serious damage of
      liver's cells with very high levels of AspAT, AIAT and LDH. Based on clinical and
      biochemical examinations we diagnosed ischemic hepatitis. The patient's clinical
      and biochemical tests were normalized after improvement of heart failure. Biopsy
      of liver was normal at that time. Prognosis in ischemic hepatitis depends on
      course of heart failure.

PMID- 9523469
TI  - [Clinical pathology and diagnostic aspects of giardiasis].
AB  - From the presented review of data on clinical pathology of giardiasis the authors
      conclude that type and variability of pattern and course of the disease are
      shaped by several factors. On one hand they are influenced by genetically
      distinct character of a given Giardia isolate, its pathogenicity, ability to
      colonize small intestine and releasing of secretory-excretory products; on the
      other hand the clinical variability reflects immune response of the host,
      development and intensity of pathomorphology in the intestine mucosa, secondary
      secretory disturbances in gastric mucosa and coexistence of pathogenic bacterial
      flora in small intestine. Application of not only the serological tests (ELISA,
      IF) to detect antibodies against Giardia but also use of tests detecting Giardia
      GSA65 co-proantigen and of analysis of parasite DNA represent significant
      progress in diagnosing Giardia invasion. The modern tests do not negate the need
      of performing morphological Giardia analysis which continues to represent a basic
      test in giardiasis.

PMID- 9523471
TI  - [Current views on the pathophysiology of bacterial meningitis--new therapeutic
      possibilities?].
AB  - Despite the introduction of numerous antimicrobial therapeutic advances, the
      morbidity and mortality associated with bacterial meningitis remain high. New
      understanding of the pathogenesis and molecular pathophysiology of bacterial
      meningitis have led to the development of innovative, adjunctive treatment
      strategies in the hopes of improving outcome from this disorders. Studies in
      animal models have demonstrated, that the inflammatory response resulting from
      bacterial invasion of the subarachnoid space is due in large part to the activity
      of host-derived mediators (cytokines). This inflammatory response is responsible
      for the long-term neurological sequelae and death associated with bacterial
      meningitis. Experimental studies have demonstrated, that attenuation of the
      inflammatory response by anti-inflammatory agents may be useful in preventing
      many of the pathophysiologic consequences of bacterial meningitis. Numerous
      potential therapeutic agents, that may limit inflammation of the subarachnoid
      space have been and are being developed, and trials in animal models and in
      humans are under way. There are: corticosteroids (dexamethasone), non-steroidal
      anti-inflammatory agents, pentoxifylline, anti-leukocyte CD-18 receptor
      antibodies, specific cytokine antagonists, antagonists of Platelet-Activating
      Factor (PAF) and others. Safe and effective agents with demonstrated efficacy as
      adjuvants to bactericidal antimicrobial agents in the therapy for bacterial
      meningitis in humans may improve the prognosis of this disease.

PMID- 9523470
TI  - [Adenosine deaminase: isoenzymes ADA1 and ADA2].
AB  - The isoenzymes ADA1 and ADA2 of the enzyme adenosine deaminase (ADA 3.5.4.4)
      deaminate mainly two nucleotides: adenosine and 2'-deoxyadenosine, molecules with
      many effects on human cells. Thus, the ADA1 and ADA2 in human cells are of
      extreme importance. Biochemical and biological properties of the isoenzymes ADA1
      and ADA2 as well as their usefulness in diagnostic of many diseases were
      described.

PMID- 9523472
TI  - [Management in cases of multiple cerebral aneurysms].
AB  - In the management of multiple intracranial aneurysms one has to face some
      problems, which do not occur in cases with single ones. The majority of
      neurosurgeons nowadays trend to operate on all detected aneurysms. Some
      controversy still exists concerning operating strategy--to operate all aneurysms
      simultaneously or in stages. Those who advocate the late way of treatment have to
      recognise which one of aneurysms was the cause of haemorrhage and must be
      operated first. This is one of the main factors influencing the results of
      treatment of multiple cerebral aneurysms.

PMID- 9523473
TI  - [Methods of evaluating physical activity in the elderly].
AB  - Various methods measuring physical activity (PA) that have been used so far in
      older population are described. Different PA questionnaires and their potential
      application in routine PA assessment in that age group are discussed.

PMID- 9523474
TI  - [August Karl Bier--one hundred years of cocaine use in spinal anesthesia].
AB  - It is a history of cocaine use by A.K. Bier in spinal anaesthesia. A.K. Bier was
      a pioneer of spinal anaesthesia with cocaine. He described his experience with
      this technique in 6 patients. This contribution was the first clinical word
      concerning a description of instruments and complication of spinal anaesthesia
      with cocaine. First in Poland who used cocaine in spinal anaesthesia was
      Franciszek Kijewski, surgeon from Warsaw.

PMID- 9523475
TI  - [Was Doctor Tadeusz Zelenski (Boy) an outstanding physician].

PMID- 9523476
TI  - [Autoimmune hepatitis and chronic hepatitis C].

PMID- 9523477
TI  - [Selected cellular immunity parameters in patients with Lesniowski-Crohn
      disease].
AB  - The study was aimed at investigating the expression of HLA-DR, CD4, CD8, CD56 and
      CD16 surface antigens on peripheral blood lymphocytes in patients with Crohn's
      disease. The percentage of rosette-forming T-cells in theophylline test was
      assessed simultaneously. The experiment at group consisted of 18 patients (aged
      16-66) of long standing Crohn's disease history, being in the remission period
      and not treated by steroid antiinflammatory drugs. The percentage of lymphocytes
      with HLA-DR, CD4, CD8, CD56 and CD16 surface antigens was examined by means of
      the monoclonal antibodies (DAKO), and the APAAP procedure. The immunological test
      included also an assessment of the number of T-cells forming active (ARFC) and
      total (TRFC) rosettes in the theophylline test. Significantly increased (p <
      0.001) percentage of lymphocytes with HLA-DR surface antigens was observed in
      patients with Crohn's disease. The percentage of lymphocytes with CD4, CD8, CD56
      and CD16 surface antigens did not differ significantly from the control group,
      although the tendency for increase in the percentage of lymphocytes with CD8
      surface antigens was clearly marked. The ratio of lymphocytes with CD4 to CD8
      surface antigens and the number of T-cells forming active and total rosettes were
      significantly lower (p < 0.05) in patients with Crohn's disease. In 10 of 18
      patients the number of T-cells forming active and total rosettes was lower than
      500 cells in 1 mm3 peripheral blood. In addition particular notice should be
      given to the fact that no T-cells reaction to theophylline was obtained in
      patients' group. The results suggest significant cellular immunoreactivity
      disturbances which may be the result of the persisting intestinal mucosa's
      inflammation in patients with Crohn's disease being in the remission period. The
      studies of peripheral blood lymphocytes with HLA-DR surface antigens may have
      significance in Crohn's disease's clinical monitoring.

PMID- 9523478
TI  - [Detection of IgA antibodies as important markers of acute primary infection with
      Toxoplasma gondii].
AB  - The diagnosis of Toxoplasma gondii infection is currently based on immunological
      tests, but tests for IgM and IgG antibodies alone are often insufficient to
      estimate the risk of active disease, especially during pregnancy and in
      immunodeficient patients. Classically the study of anti-toxoplasma immunity
      involves titration of IgG antibodies, which reflect immunity to the parasite, and
      IgM antibodies which of present, reveal acute infection. However, technical
      advances have shown the limitations of these tests as tests for IgM can be
      positive because of residual specific IgM or even in subjects free of acute
      infection due to the existence of natural interfering IgM. In addition, IgM can
      be absent in children with congenital toxoplasmosis or subjects with secondary
      reactivation. The purpose of our study was to evaluated of IgA antibodies to T.
      gondii in serum samples which were positive in screening test. Our results
      confirm the diagnostic value of testing for anti-toxoplasma IgA antibodies. These
      antibodies are absent in uninfected subjects and are detected rapidly after
      primary infection. The determination of IgA complements IgM determination for the
      diagnosis of toxoplasmosis.

PMID- 9523479
TI  - [Resistance to antibiotics of Streptococcus pneumoniae strains].
AB  - Streptococcus pneumoniae strains are exhibiting increasing rates of antibiotics
      resistance. A rapid increase of resistance was seen not only to penicillin but
      also other antimicrobial agents and therefore this paper describes the study of
      resistance and multiresistance of pneumococci to 7 antibiotics: penicillin (P),
      erythromycin (E), clindamycin (CC), tetracycline (T), co-trimoxazole (SXT),
      cefotaxime (CTX) and vancomycin (Va), using the disk-diffusion technique
      according to NCCLS procedure. We tested a total of 218 S. pneumoniae strains
      isolated from various materials: from sputum (54), noses (117), throats (28) and
      different swabs specimens (19). The overall percentage of resistant isolates to
      penicillin was 3.7%, to erythromycin--4.1%, to clindamycin--10.6%, to
      tetracycline--17.4%, to co-trimoxazole--15.6%, to cefotaxime--2.3%. In the sputum
      was most the monoresistant strains (66.7%). The multiresistance was highest in
      the penicillin resistant pneumococci. With the exception of vancomycin, the
      number of resistant strains to non-beta-lactam antibiotics (erythromycin,
      clindamycin, tetracycline, co-trimoxazole) was higher in penicillin-resistant
      strains compared with penicillin susceptible isolates. All isolates were
      susceptible to vancomycin.

PMID- 9523480
TI  - [Chlamydia trachomatis in imminent premature deliveries].
AB  - In the period od February-August 1995 fifty-two pregnant women treated for
      imminent premature deliveries were tested. Among 18 of them (34.6%) presence of
      chlamydial antibodies were found. The premature rupture of membranes occurred in
      19.2% of women with positive Ch. trachomatis test results (p < 0.05).

PMID- 9523481
TI  - [Cytometric analysis of lymphocyte phenotype in cord and newborn blood].
AB  - At birth and in early childhood, phenotypic and functional investigation of the
      immune system is often necessary to identify primary immunological disorders and
      may provide additional diagnostic and prognostic information in certain
      intrauterine infections. We compared, using of flow cytometric immunophenotyping,
      a broad panel of lymphocyte subsets in paired samples obtained from healthy
      infants at birth (cord blood) and at 3 days of age. Results were compared to
      those of normal children (7 to 17 years) evaluated using the same methods.
      Significant age-related differences were demonstrated in lymphocyte
      subpopulations. Our data can be used as age-matched reference values for blood
      lymphocyte immunophenotyping.

PMID- 9523482
TI  - [Results of treatment with interferon for chronic hepatitis B in children].
AB  - 8 children with chronic hepatitis B were treated with interferon, 3 M.U.
      subcutaneously three times a week for 4-5 months. Seroconversion from HBe antigen
      to anti HBe antibodies was observed in 3 of them and in 1 also seroconversion
      from HBs antigen to anti HBs antibodies. In remaining 5 cases the therapy was
      ineffective which could be caused by: more advanced inflammatory lesions in
      liver, infection with HB in infancy and low activity of aminotransferases before
      the treatment. Side effects of interferon were only transitory and in no case
      caused cessation of the therapy.

PMID- 9523483
TI  - [The effect of substance P on collagen concentration in rat colon].
AB  - Anastomotic leakage is the main reason of high mortality in colorectal surgery.
      The healing of anastomosis is predominantly derived from collagen fibrils.
      Substance P causes the proliferation of fibroblasts and connective tissue. The
      effect of SP on postoperative changes of collagen concentration was measured
      around the anastomotic side in rats. The studies shows, that SP induces a
      significant decrease in collagen synthesis in colon.

PMID- 9523484
TI  - ["Reversible cholelithiasis" in patients with chronic renal failure treated with
      ceftriaxone].
AB  - Patients with chronic renal failure were admitted to the Neurological Department
      and symptoms of cholelithiasis were observed. Ceftriaxone therapy in one case was
      clinically effective.

PMID- 9523486
TI  - [Etiology of Wilson's disease].

PMID- 9523485
TI  - [Gynecologic diagnostic problems in women with porphyria].
AB  - In the study shows case of acute porphyria in 27 year old women, admitted to
      hospital with suspicion of rupture extrauterine pregnancy. We shows difficulties
      in diagnosis associated with polysymptomatology of signs. Authors considered,
      that urines getting dark trial could improve process of reaching the diagnosis of
      porphyria, which could often protected patient from exploratory laparotomy
      getting worse a prognostication.

PMID- 9523487
TI  - [Endoscopic polypectomy in the large bowel--the pathologist's view].
AB  - Colonoscopy remains the main diagnostic tool in colorectal diseases. Endoscopic
      polypectomy is a routine therapeutic method for colorectal adenomas, but its
      yield must be verified histologically. Complete endoscopic and histologic
      resection of an adenoma is regarded as a sufficient method of its treatment. Some
      early colon cancers can also be managed endoscopically, providing that strict
      histologic criteria are fulfilled. It is the duty of clinicians to supply
      pathologists with all the clinical data on the patient and to properly mark the
      resected specimen. Pathologists must understand the therapeutic technique, its
      limits, and provide physicians with a detailed histopathological report that
      includes not only a proper histological assessment of the resected tissue, but
      also a comment on completeness of the neoplasm resection. This article should
      help both clinicians and pathologists to benefit from the potential of
      histological examination.

PMID- 9523488
TI  - [The role of some cytokines in the physiology of proliferation of hematopoietic
      cells].
AB  - Cytokines are of great importance in the regulation of proliferation of
      haematopoietic system cells. Most of known cytokines stimulate the proliferation
      of cells of granulocyte-macrophage, monocyte, and lymphocyte system. Some of them
      stimulate the proliferation of cells from erythrocyte, eosinophil and
      megakaryocyte systems and proliferation of B and T lymphocytes.

PMID- 9523489
TI  - [Cytokines in certain proliferative diseases of the hematopoietic system].
AB  - Some cytokines playing a great role in the proliferation of neoplastic
      haematopoietic system cells were described. Most of cytokines stimulate the cell
      proliferation in non-lymphoblastic leukemia, less of them act in lymphocytic
      leukemia and least in the other proliferative diseases of haematopoietic system.

PMID- 9523490
TI  - How should we evaluate health status? A comparison of three methods in patients
      presenting with obstructive sleep apnoea.
AB  - The purpose of this paper is to compare three approaches to the measurement of
      patient-reported health status which produce summary scales of health status: the
      Patient-generated Index (PGI) is a measure of individual quality of life (QoL),
      the EuroQol is a measure of QoL the results of which are weighted by utility
      values gained from community surveys and the SF-36 which produces two summary
      scales of health status (the physical component summary (PCS) and the mental
      component summary (MCS) scores). A follow-up interview survey of patients with
      obstructive sleep apnoea (OSA) was conducted. The patients received continuous
      positive airways pressure therapy (CPAP) between the two administrations of the
      questionnaires. One hundred patients presenting with OSA and who were suitable
      for CPAP therapy were asked if they would take part in the study. The results on
      the PGI, EuroQol EQ-5D utility weighted scores and 'thermometer' scores and SF-36
      physical and mental summary scores were measured. Eighty-nine respondents
      provided sufficient data to calculate PGI and EuroQol scores and 86 patients
      provided sufficient data to calculate SF-36 summary scores. The PGI indicated
      substantial improvement after CPAP treatment whereas the EuroQol indicated little
      or no improvement on either utility weighted or thermometer scores. The SF-36 PCS
      and MCS scores were lower than those of the general population at baseline, but
      had improved to the normative levels after treatment. The EuroQol provided a
      substantially different picture of change to either of the ones gained from the
      SF-36 or PGI. It is suggested that the EuroQol does not contain questions which
      relate to important aspects of health and well-being and may not accurately
      reflect the health state of individuals. Consequently, caution must be exercised
      to assure that an appropriate instrument has been employed when using health
      outcomes data to assess or prioritize available health care treatments.

PMID- 9523491
TI  - Evaluation of a population-based measure of quality of life: the Health and
      Activity Limitation Index (HALex).
AB  - This paper briefly discusses the rationale and methods for developing and
      evaluating the Health and Activity Limitation Index (HALex), a generic measure of
      health that consists of two attributes: perceived health and activity limitation.
      Using a multiattribute utility scoring system, information from these attributes
      was combined to form a single score that represents health-related quality of
      life (QoL) on a 0.0-1.0 continuum. The construct and incremental validity are
      evaluated using data from a sample of over 40,000 adults who participated in the
      1990 US National Health Interview Survey. The health state distributions for
      known groups, defined in terms of personal or lifestyle characteristics such as
      sex, age and smoking status, were comparable to those for similarly defined
      states that have been studied by other researchers. Of the regression models
      examined in this analysis, age, years of schooling and being in a high-risk group
      based on body mass index (BMI) were found to have the largest impact on health as
      measured by the HALex. Although this measure was developed to be combined with
      mortality data to form a quality-adjusted life year (QALY) for detecting changes
      in the health of the US population from 1990 to 2000, it may also be useful for
      inclusion in clinical studies, in particular as the national data are readily
      available for use as norms.

PMID- 9523492
TI  - Health-related quality of life following liver transplantation.
AB  - The objectives of this study were to report on the health-related quality of life
      (QoL) experienced by patients following liver transplantation and to investigate
      the factors associated with its variation. A questionnaire comprising the SF-36
      and EuroQol EQ-5D instruments was sent by post to 147 patients who had received a
      liver transplant, indicated by a chronic liver disease, in the previous 8 years.
      The scores of the respondents were compared to population norm scores. The
      variation in both the SF-36 and EQ-5D scores was explored. Many liver transplant
      patients experienced most satisfactory QoL levels post-transplantation although,
      in general terms, the levels were poorer than those seen in the general
      population. The variation in the post-transplant health-related QoL scores was
      found to be associated with a number of pre-transplant factors: disease severity
      (proxied by Child Pugh class), disease duration at the time of transplantation
      and liver transplant history (whether the patient had received a single or
      multiple transplants). In making clinical decisions about the use of
      transplantation for chronic liver diseases, consideration should be given to the
      key factors likely to affect subsequent health-related QoL.

PMID- 9523493
TI  - Construct validation of the USA-Spanish version of the SF-36 health survey in a
      Cuban-American population with benign prostatic hyperplasia.
AB  - This study examined the USA-Spanish version of the SF-36 health survey (validated
      in Mexican-Americans) and tested its construct validity in Cuban-Americans with
      benign prostatic hyperplasia (BPH). The study evaluated the SF-36 and American
      Urological Association (AUA) Symptom Index scores of 264 individuals with BPH.
      Individuals were assigned to one of the following groups: non-Hispanics who
      received the English version, Cubans who received the English version and Cubans
      who received the Spanish version. The objective was to determine the correlation
      between the individuals' SF-36 and AUA Symptom Index scores. It was expected that
      patients in the severe category would have the lowest quality of life (QoL)
      scores. The analysis was conducted using a MANOVA with a planned comparisons
      procedure. For all eight scales, the English and Spanish versions of the SF-36
      were able to classify individuals with mild/moderate symptoms of BPH as having
      statistically higher QoL scores than those with severe symptoms of BPH. We
      concluded that the USA-Spanish version of the SF-36 can differentiate between
      levels of symptom severity in individuals with BPH. More importantly the
      construct validity of the English and Spanish versions of the SF-36 was
      demonstrated through significant correlation with the theorized constructs.

PMID- 9523494
TI  - Psychometric performance of the Asthma Quality of Life Questionnaire in a US
      sample.
AB  - The purpose of this study was to examine the psychometric characteristics of the
      Juniper Asthma Quality of Life Questionnaire (AQLQ) in a sample of asthmatics
      from the USA, employing data from the Asthma Symptom Utility Index (ASUI)
      validation study. One hundred and sixty-one adults (66 men) undergoing standard
      care in an asthma clinic participated in the study (mean age = 34.7 +/- 10.7
      years, mean duration of illness = 17.3 +/- 11.22 years and mean FEV1% predicted =
      85.6% +/- 17.1%). The internal consistency reliability (infinity) ranged from
      0.90 (environment subscale) to 0.95 (overall score) and the 2 week
      reproducibility (ICC) ranged from 0.81 (activities subscale) to 0.93 (symptoms
      subscale). The AQLQ was significantly correlated with an asthma disease severity
      scale and the Health Utilities Index (p < 0.001). No relationship was found
      between the AQLQ score and FEV1% predicted. Men reported better overall quality
      of life (QoL), fewer activity limitations and less environmental exposure than
      women (p < 0.01), while patients with a high school education or less had more
      severe asthma and poorer QoL across all subscales (p < 0.001). This may reflect
      the differential experiences of asthma across gender and socioeconomic groups.
      The results suggest that the AQLQ may be a useful outcome measure for clinical
      trials conducted in the USA.

PMID- 9523495
TI  - Disease-specific quality of life: is it one construct?
AB  - The objective of this study was to examine the structure of disease-specific
      quality of life (QoL). Models of QoL with either one overall construct or more
      constructs were tested and the relationships (factor loadings) between the
      constructs and dimensions were established, using structural equation modelling.
      The models were tested over time to assess the stability of the structure. To
      generalize the results further, disease-specific questionnaires of two very
      different chronic diseases have been compared: inflammatory bowel disease (IBD)
      and Parkinson's disease (PD). Questionnaires were mailed in 1994 and a repeated
      measurement was conducted in 1995. Data were obtained from 222 IBD patients and
      235 PD patients. The results show that for both diseases, disease-specific QoL
      can be considered as one construct. The stability over time of the structure of
      the QoL models was satisfactory. In PD the factor loadings between the dimensions
      and QoL were within a small range and remained the same over time, while in IBD,
      the factor loadings had a larger range and fluctuated more. These results imply
      that one meaningful sum score can be obtained from these questionnaires.

PMID- 9523496
TI  - The international development of the RGHQoL: a quality of life measure for
      recurrent genital herpes.
AB  - This paper describes the international development and psychometric testing of
      the Recurrent Genital Herpes Quality of Life Questionnaire (RGHQoL), a condition
      specific quality of life (QoL) instrument. The theoretical foundation for the
      measure is the needs-based model of QoL and the content of the instrument was
      derived from in-depth qualitative interviews with relevant patients in the UK.
      Versions of the RGHQoL were required for the UK, USA, Italy, Germany, France and
      Denmark for use in international clinical trials. The results indicate that the
      final 20 item measure has good reliability, internal consistency and validity for
      all language versions. A small responsiveness study in Denmark suggested that the
      measure is sensitive to changes in QoL associated with the initiation of
      suppression treatment for recurrent genital herpes (RGH). It is concluded that
      the RGHQoL is a valuable instrument for inclusion in clinical trials. The
      psychometric properties of the instrument are such that it may also be used to
      monitor the progress of individual patients.

PMID- 9523497
TI  - Comparison of the EQ-5D and SF-12 in an adult US sample.
AB  - The purpose of this paper is to discuss the results of a direct comparison of two
      instruments, the SF-12 health survey and the EuroQol Group's EQ-5D, in a sample
      drawn from the adult US population. The data were collected via a survey
      instrument mailed to 1,800 subjects in the USA. The instrument contained the EQ
      5D valuation questionnaire and the items of the SF-12. In addition, the subjects
      were asked to provide demographic information, complete a depression screening
      item and to indicate if they had any of seven common chronic conditions. The
      usable response rate was 23.7%. Patients indicating a health problem on the EQ-5D
      had significantly lower mean SF-12 component scores (i.e. MCS-12 and PCS-12) for
      all dimensions. As was expected, the relationships were stronger between the EQ
      5D functional dimensions and the PCS-12 and between the MCS-12 and the EQ-5D
      anxiety/depression dimension. The EQ-5D visual analogue scale (VAS) scores were
      positively correlated with both component scores; r = 0.55 for PCS-12 and r =
      0.41 for MCS-12. The results of this investigation provide support for the
      validity of both the EQ-5D and the SF-12 as descriptive measures of health
      status. The measurements by both instruments behaved in patterns that were
      consistent with recognized sociodemographic differences in health status. The
      limitations of the dimensional structure of the EQ-5D were somewhat overcome by
      the use of the VAS, which may also be possible with a constructed index score
      based on explicit values derived from a general population. The SF-12 appeared to
      be more sensitive to differences associated with less severe morbidity.

PMID- 9523498
TI  - The development and testing of the well-being index for surgical patients (WISP).
AB  - The development and testing of the Well-being Index for Surgical Patients (WISP),
      an instrument designed to assess the well-being of patients between 1 and 4
      months after abdominal surgery, is described. The measure was intended for use in
      a study of the effectiveness of a dietary supplement for patients undergoing such
      surgery. Interviews were conducted with 15 patients who had had abdominal
      operations between 1 and 4 months previously. They provided information about
      their well-being at the time of their interview and also during the period since
      they had been discharged from hospital. A draft questionnaire was derived from
      the interviews and field tested with a further 17 patients who found the content
      to be relevant and the questionnaire easy to complete. A further 44 patients
      completed the measure on three occasions; 1, 2 and 4 months after abdominal
      surgery. The instrument was shown to have good internal consistency and produced
      statistically significant improvements in well-being over time. A postal survey
      with 20 patients indicated that the instrument's test-retest reliability was
      adequate. The WISP is acceptable to patients and easy to administer, making it
      suitable for inclusion in clinical trials.

PMID- 9523500
TI  - Finally! The TennCare bureau releases new data on program.

PMID- 9523501
TI  - Physician-patient communication: does it matter?

PMID- 9523499
TI  - Quality of life assessment by community pharmacists: an exploratory study.
AB  - Implicit in the evolving role of pharmacy is that its practitioners embrace the
      concept of quality of life (QoL). In recent years there has been an increased
      interest in incorporating health-related quality of life (HRQoL) measures into
      clinical practice, primarily focusing on the physician as the user of this
      information. Pharmacists may be able to use these instruments in their practices
      to provide better pharmaceutical care. To explore the feasibility of such an
      undertaking, questionnaires were mailed to a national sample of community
      pharmacies. In addition to the questionnaire, the respondents were provided with
      examples of two instruments: the Duke Health Profile and the QOLIE-10. A
      definition of HRQoL was provided to the respondents. After two mailings and a
      reminder postcard, a usable response rate of 27.2% was achieved. The results
      revealed that over 80% of the respondents currently discuss HRQoL issues with
      their patients. In addition, 66% reported that they attempt to assess the HRQoL
      of their patients, albeit usually on a subjective, informal basis. After viewing
      examples of HRQoL instruments, over three-quarters of the respondents reported a
      willingness to use HRQoL assessment tools in their practices. However, only 53.7%
      of the respondents were familiar with the concept of HRQoL. Less than 5% reported
      familiarity with formal instruments. The self-reported knowledge of pharmacists
      concerning HRQoL was low and the respondents recognized a significant gap between
      their current knowledge and the level of knowledge needed to assess the HRQoL of
      their patients formally. The results suggest a possible role for the pharmacist
      in HRQoL assessment. However, the use of HRQoL instruments in community
      pharmacies will require further training and education on the part of pharmacists
      concerning the concept of HRQoL, the issues involved in its measurement and how
      they can use HRQoL information in their practices. In addition, a number of
      unanswered questions must be addressed through the research process in order for
      HRQoL questionnaires to become clinical tools in the practice of pharmacy.

PMID- 9523502
TI  - Not always right--never in doubt.

PMID- 9523505
TI  - Episodic unilateral mydriasis and headaches.
AB  - When anisocoria is associated with headaches, it usually heralds serious central
      nervous system pathology such as tumors, aneurysms, or herniation. But when a
      patient has isolated, episodic unilateral mydriasis and migraine, such a patient
      may be reassured and further workup undertaken only if symptoms worsen or change.
      We present a 17-year-old who had severe headaches and episodic pupillary
      dilation, and review the current literature on the topic.

PMID- 9523504
TI  - Human sequelae of severe carbamate poisoning.
AB  - Carbofuran is a carbamate that functions as a cholinesterase inhibitor.
      Accidental or intentional ingestion can produce a life-threatening syndrome that
      requires prompt diagnosis and treatment. We describe a case of intentional
      carbofuran ingestion that resulted in coma, respiratory failure from acute
      respiratory distress syndrome (ARDS), and cortical blindness.

PMID- 9523506
TI  - An intrahepatic biloma following a gunshot wound to the liver.

PMID- 9523507
TI  - A case of paraquat poisoning.

PMID- 9523508
TI  - Shaken baby syndrome--don't shake that baby!

PMID- 9523509
TI  - Expanded programme on immunization (EPI). Progress towards poliomyelitis
      eradication, 1994-1997.

PMID- 9523510
TI  - CHD technical briefings at WHO headquarters.

PMID- 9523511
TI  - Recommended composition of influenza virus vaccines for use in the 1998-1999
      season.

PMID- 9523512
TI  - Surgical and research aspects of inflammatory bowel disease: introduction.

PMID- 9523513
TI  - Proctocolectomy and ileostomy to pouch surgery for ulcerative colitis.
AB  - The development of continence-preserving and sphincter-preserving procedures for
      operation of ulcerative colitis has a long and interesting history. Reported
      clinical results on the continent ileostomy (Kock pouch) and the pelvic pouch
      procedure have often been enthusiastic; and when confronted with the options
      patients have mostly been in no doubt in selecting "the best operation." However,
      even if the continent ileostomy and subsequently restorative proctocolectomy were
      great innovations, it is by no means obvious that they should be recommended as
      the first choice for all patients. For patients old enough to join in a
      responsible discussion the pros and cons of the various operations available
      today must first be carefully described and a decision reached that reasonably
      meets the patient's wishes and that seems to the surgeon to be soundly based.
      When comparing the postoperative morbidity, long-term outcome, and quality of
      life assessment of the options, such a decision is in fact far from easy. Thus
      panproctocolectomy and ileostomy for ulcerative colitis can be considered a
      comparatively safe, predictable operation that can cure the patient and allow a
      short hospital stay, a quick recovery, and rehabilitation. It should also enable
      the patient to be free of hospital supervision after a year or so. Although there
      is a major change in body image and sexual disturbances may occur, the operation
      is in fact still the yardstick by which the other options should be compared.
      Despite the great attraction of rectum- and sphincter-preserving operations,
      there will always be patients for whom panproctocolectomy and a conventional end
      ileostomy is the superior alternative. The ileal pouch operations are technically
      demanding and should probably best be restricted to specialist centers even in
      the future. Complications, if they arise, are often serious, and the hospital
      stay is often counted in weeks. The functional result may be good, but defects in
      continence are common and sexual dysfunction is a problem for many of these
      patients. The pouchitis syndrome is a great disappointment, and recent reports on
      subsequent epithelial dysplasia and even development of cancer are alarming. The
      long-term results are in this respect still uncertain. Careful patient selection,
      with full discussion with the patient and his or her family are essential before
      a decision on a continent ileostomy or a pelvic pouch is reached. Strong
      motivation toward avoidance of a conventional ileostomy is important. When
      compared with the imperfect functional results and the high morbidity associated
      with the pelvic pouch procedure, there is at present a great revival of interest
      for total colectomy with ileorectal anastomosis. It is still a useful operation
      and should be seriously considered particularly in the young. The functional
      results are comparatively good. Sexual function is well preserved. The use of the
      operation may enable the teenager to regain good health and finish education and
      family planning. Due to the cancer risk the need for subsequent supervision must
      be made clear, however. The operation may also be valuable in elderly patients
      who would be much bothered by an ileostomy and who are unlikely to live long
      enough for carcinoma to become a problem. The great advantage is that should a
      failure occur the other options remain.

PMID- 9523514
TI  - Reconstructive surgery for pelvic pouches.
AB  - Restorative proctocolectomy with ileo-pouch-anal anastomosis has become the
      elective surgical procedure of choice for most of our patients with ulcerative
      colitis and for selected patients with familial adenomatous polyposis. This
      report reviews the results of the outcome of patients who have undergone a more
      radical reconstructive approach for salvage of the pelvic pouch where multiple
      local procedures have failed. A group of 24 patients were reviewed (19 females, 5
      males). The indication for surgery was ulcerative colitis in 22 patients; 10 of
      the 24 patients were referred from other centers. The 24 patients underwent a
      mean of 2.9 local salvage procedures per patient. Of the 19 females within the
      group, 12 had an anastomotic vaginal fistula. The 24 patients were divided into
      two groups. The first group consisted of 14 patients whose initial pouch was used
      once again for revisionary surgery. Group 2 comprised 10 patients whose initial
      pouch was removed and a redo pouch was constructed. Of the 24 patients, only 2
      have had their pouches removed. More than 75% of the patients have had a
      successful outcome using a reconstructive approach. Four patients still have an
      ileostomy; of these four, two are awaiting closure of their loop ileostomy. Of 18
      patients who were evaluable, 13 were considered to have normal daytime
      continence, and 17 of 18 were sexually functional. Of the 18 evaluable patients,
      15 were satisfied with the outcome. Radical reconstructive surgery can be
      performed where local procedures to effect pouch salvage have failed, and it
      should be considered as a first-line management where factors dictate that local
      procedures might fail. The commitment of the surgeon and the patient to achieving
      a successful outcome is essential. Severe pouch-specific complications can be
      managed successfully by surgeons who have a specific interest in pelvic pouch
      surgery and have considerable experience dealing with complications that arise.

PMID- 9523515
TI  - Pouchitis: risk factors, etiology, and treatment.
AB  - A Medline literature review of pouchitis has been conducted, and relevant
      information from this search and the authors' own experience has been used to
      produce an overview on pouchitis at the current time. Particular attention is
      given to etiology, pathophysiology, and clinical management.

PMID- 9523516
TI  - Cancer and inflammatory bowel disease: bias, epidemiology, surveillance, and
      treatment.
AB  - Individuals with chronic ulcerative colitis are at increased risk of developing
      colorectal carcinoma, particularly if there is long-standing disease or extensive
      colitis. It is generally accepted that the risk of colorectal cancer does not
      begin until 8 to 10 years after the time of diagnosis of ulcerative colitis.
      Thereafter it increases by approximately 0.5% to 1.0% per year. In patients with
      Crohn's disease, the risk of malignancy is smaller and less well defined. The
      most significant predictor of the risk of malignancy in patients with
      inflammatory bowel disease is the presence of dysplasia in colonic biopsies.
      There is considerable controversy in the literature regarding the efficacy of
      colonoscopic surveillance programs and the role of prophylactic surgery to
      prevent colorectal cancer. Surveillance certainly fails to detect carcinoma in
      some patients who are having regular colonoscopy. Concerns have also been raised
      as to the cost-benefit of colonoscopic surveillance in patients with colitis.
      Randomized controlled trials of surveillance programs are highly unlikely in view
      of the low prevalence of IBD in the population, the long period of observation
      required, and the probability of contamination of surveillance programs by
      colonoscopy for assessment of disease activity. Despite the lack of clear
      guidelines, surveillance colonoscopy and biopsy continues to be widely practiced.
      Research is proceeding to identify genetic and biochemical markers that may prove
      clinically useful for predicting cancer risk. At present, however, surveillance
      programs are likely to continue according to institutional practice. It is
      important for those participating in such programs to be aware of the limitations
      of colonoscopy and biopsy as a means of reducing the risk of cancer in
      inflammatory bowel disease.

PMID- 9523517
TI  - Strictureplasty for Crohn's disease: techniques and long-term results.
AB  - Strictureplasty for treatment of symptomatic intestinal strictures secondary to
      Crohn's disease is being performed with increasing frequency. To determine the
      overall clinical results after strictureplasty for Crohn's disease, all patients
      undergoing this procedure were prospectively studied. Between 6/1/89 and 2/1/97,
      57 Crohn's disease patients underwent 60 operations utilizing strictureplasties.
      A total of 109 strictureplasties were performed (90 Heineke-Mikulicz, 6 Finney,
      and 13 side-to-side isoperistaltic). The 30-day perioperative morbidity was 12%,
      with complications being less common for patients undergoing elective versus
      unscheduled operations (p < 0.002). Recurrence of Crohn's disease requiring
      operation was seen in seven patients after a mean follow-up of 38 months. The
      estimated cumulative recurrence rate after 2 years was 15 +/- 6% (+/- standard
      error) and 22 +/- 10% at 5 years. A recurrence developed at the site of the
      previous strictureplasty in only five cases. Strictureplasty is a safe, effective
      means of providing long-term surgical palliation to selected patients with
      Crohn's disease. Perioperative complication rates are comparable to those seen
      with standard surgical treatment, and recurrences are not excessive.

PMID- 9523518
TI  - Factors determining recurrence following surgery for Crohn's disease.
AB  - Many factors have been examined in an attempt to define groups at higher risk for
      recurrence or recrudescence of Crohn's disease. Among these factors are age and
      onset of disease, gender, site of disease, number of resections, symptomatic
      status at the time of surgery, length of small bowel resection, fistulizing
      versus obstructive forms of disease, proximal margin length, microscopic margin
      histology, strictureplasty, and number of sites of disease, as well as the
      presence of colonic only disease, the presence of granulomas, blood transfusions,
      family history, and prophylactic treatment. To date, only proctocolectomy with
      Brooke ileostomy versus other procedures for colonic only disease, and
      prophylactic treatment have been shown with some degree of confidence to lead to
      a lower recurrence rate after surgery for Crohn's disease.

PMID- 9523519
TI  - Laparoscopy for inflammatory bowel disease: pros and cons.
AB  - The role of laparoscopic surgery in the treatment of colorectal malignancies is
      still under investigation, although it can offer significant benefits to many
      patients with inflammatory bowel disease (IBD). The aim of this study was to
      assess the pros and cons of the laparoscopic management of IBD. Data were
      obtained from a review of the literature published since 1992, when the first
      report of laparoscopic surgery for IBD appeared in print. From 1992 to 1997
      several series of laparoscopic colorectal surgery for the management of IBD have
      been reported. A close evaluation of these studies revealed that laparoscopy in
      patients with terminal ileal Crohn's disease or anal Crohn's disease in need of
      fecal diversion offers significant advantages compared to laparotomy, including
      decreased pain, length of hospitalization, and disability. An additional bonus is
      improved cosmesis and a reduction in symptomatic postoperative adhesions. These
      many benefits can be achieved without any increase in morbidity or expense.
      Conversely, the use of this technology for restorative proctocolectomy in
      patients with mucosal ulcerative colitis is associated with a longer operative
      time and an increased incidence of both intra- and postoperative complications
      compared to laparotomy. Laparoscopic colorectal surgery can thus be advantageous
      for treatment of terminal ileal Crohn's disease but cannot be routinely justified
      for the treatment of mucosal ulcerative colitis.

PMID- 9523520
TI  - Quality of life of patients with inflammatory bowel disease after surgery.
AB  - Quality of life is an important outcome measure following surgery for ulcerative
      colitis. Quality of life incorporates not only the physical or functional
      outcome; it also considers the emotional and social well-being of patients.
      Quality of life may be measured using disease-specific or generic quality of life
      measures or by utility measurement. Although the pelvic pouch procedure is
      preferred by most patients, there are data to suggest that the quality of life is
      excellent irrespective of the procedure, possibly because physical well-being is
      improved and is the main determinant of outcome. Those who have a pelvic pouch
      may be less restricted in some activities. Compared to medically treated
      patients, quality of life is usually superior in surgical patients, although it
      varies depending on the activity of the disease and the surgical outcome. Despite
      more publications on this topic in recent years, there is a need for further
      studies comparing quality of life in patients receiving medical and surgical
      treatment as well as assessing outcome following the various surgical procedures.

PMID- 9523521
TI  - Cytokines in inflammatory bowel disease.
AB  - Cytokines play a central role in the modulation of the intestinal immune system.
      They are produced by lymphocytes (especially T cells of the Th1 and Th2
      phenotypes), monocytes, intestinal macrophages, granulocytes, epithelial cells,
      endothelial cells, and fibroblasts. They have proinflammatory functions
      [interleukin-1 (IL-1), tumor necrosis factor (TNF), IL-6, IL-8, IL-12] or
      antiinflammatory functions [interleukin-1 receptor antagonist (IL-1ra), IL-4, IL
      10, IL-11, transforming growth factor beta (TGF beta)]. Mucosal and systemic
      concentrations of many pro- and antiinflammatory cytokines are elevated in
      inflammatory bowel disease (IBD). An imbalance between proinflammatory and
      antiinflammatory cytokines was found for the IL-1/IL-1ra ratio in the inflamed
      mucosa of patients with Crohn's disease, ulcerative colitis, diverticulitis, and
      infectious colitis. Furthermore, the inhibition of proinflammatory cytokines and
      the supplementations with antiinflammatory cytokines reduced inflammation in
      animal models, such as the dextran sulfate colitis (DSS) model, the
      trinitrobenzene sulfonic acid (TNBS) model, or the genetically engineered model
      of IL-10 knockout mice. Based on these findings a rationale for cytokine
      treatment was defined. The first clinical trials using neutralizing monoclonal
      antibodies against TNF alpha (cA2) or the antiinflammatory cytokine IL-10 have
      shown promising results. However, many questions must be answered before
      cytokines can be considered standard therapy for IBD.

PMID- 9523522
TI  - Experimental studies on the effect of lidocaine on wound healing.
AB  - Local anesthetics have several effects on wound healing. In experimental studies,
      procaine at high concentrations has been proved to retard healing in surgical
      wounds by diminishing the synthesis of mucopolysaccharides and hence probably
      collagen. Other studies have shown that lidocaine and bupivacaine inhibit
      collagen synthesis in fibroblast tissue cultures in rats. This study was designed
      to evaluate the effect of lidocaine on wound healing. An experimental,
      prospective, comparative, crossover and double-blind study was designed. Forty
      male guinea pigs, weighing 300 to 600 g, were randomly assigned to two groups. In
      control group A (20 animals), skin and subcutaneous tissue in a clean wound were
      incised and infiltrated with regular saline solution; in group B 20 animals were
      infiltrated with 1% lidocaine. All animals were sacrificed on day 8 and evaluated
      for breaking strength, number of collagen fibers by morphometry, and histologic
      examination of collagenization, edema, vascularity, and presence of acute and
      chronic inflammatory cells. The histopathologic appearance of tissues infiltrated
      with lidocaine did not vary consistently in relation to collagenization, edema,
      or acute and chronic inflammatory processes. The mean breaking strength between
      both groups was not statistically significant (p = 0.120). Important statistical
      differences were observed in vascularity (p < 0.003) and morphometric results (p
      < 0.001), where collagen was found in small amounts in the lidocaine group. The
      results of this study suggest that local infiltration of lidocaine produces
      significant histopathologic changes, but it does not substantially alter wound
      healing as there were no differences in the breaking strength of the wounds.

PMID- 9523523
TI  - Determinants of survival following hepatic resection for metastatic colorectal
      cancer.
AB  - Hepatic resection remains the only potentially curative treatment for metastatic
      colorectal cancer. This retrospective review study was undertaken in an attempt
      to identify factors that influence patient survival following hepatic resection
      for metastatic colorectal cancer. From January 1978 to December 1993, a total of
      301 patients underwent a total of 345 planned hepatic resections for metastatic
      colorectal cancer. Of those, 245 patients had one resection, 44 had two
      resections, and 12 had three resections. For all patients the overall median
      survival was 20.6 months, operative mortality was 1.1%, and overall morbidity was
      17.2%. Average hospital stay was 9 days. Statistical analysis included univariate
      analysis using log rank comparisons, Kaplan-Meier survival curves, and
      multivariate analysis using Cox proportional hazards regression. The
      statistically significant factors that influenced survival were distribution of
      liver metastases, unilobar versus bilobar (p = 0.0001), resected versus
      nonresected (p < 0.0001), and tumor-free surgical margins versus positive margins
      (p = 0.001). Surprisingly, the disease-free interval and the original stage of
      the primary tumor did not predict survival (p = not significant). Other factors
      that had no influence on survival were type of resection, size and number of
      liver metastases, ABO blood group, and the number of perioperative blood
      transfusions. For those patients who underwent resection of unilobar metastases
      with tumor-free margins, the 5-year survival rate was 29% with a median survival
      of 35 months and eight survivors > 7 years. In addition, one patient with bilobar
      disease had survival > 7 years and five patients who had resection of hepatic
      metastases and extrahepatic cancer simultaneously had survival > 3 years. Our
      data support the concept that patients with unilobar metastatic disease who
      undergo surgical resection with tumor-free surgical margins can be afforded a
      significant opportunity at long-term survival with acceptable morbidity,
      mortality, and hospital stay. Also, certain patients with bilobar or extrahepatic
      disease (or both) who undergo complete resection can enjoy a long-term survival.
      In these subgroups of patients resection should be considered on an individual
      basis.

PMID- 9523524
TI  - Hepatic resection in the elderly.
AB  - From 1986 to 1995 a total of 97 patients > 65 years of age underwent hepatic
      resections at the Department of General Surgery, Hospital Lainz, Vienna, Austria.
      The population consisted of 39 men and 58 women with a mean age of 74.0 +/- 5.5
      years. Primary neoplasia of the liver was the cause of resection in 35 patients,
      gallbladder cancer in 16 patients, and metastatic disease to the liver (due to
      colorectal cancer in 70%) in 40 patients. The rate of major resections (> or = 3
      liver segments) was 96% for primary neoplasia of the liver, 70% for metastatic
      disease to the liver, and 50% for gallbladder cancer; the associated mortality
      rates were 23%, 2.5%, and 25%, respectively. The magnitude of the resection had a
      significant influence on survival for gallbladder cancer (p = 0.02) and for
      primary neoplasia of the liver (p = 0.002) but not for metastatic disease to the
      liver. This reflects the high rate of cirrhosis in hepatocellular and
      cholangiocellular carcinoma (88%) and gallbladder cancer (37.5%). Both pre- and
      postoperative severe liver dysfunction had a significantly higher risk for
      postoperative mortality and morbidity, which showed an incremental risk with age.
      Another organ system able to predict outcome at the beginning of treatment by its
      moderate severe dysfunction were the lungs. Overall, only right and extended
      right lobectomies carried a significantly higher risk for postoperative mortality
      and morbidity. Postoperative complications were recorded in 43% of our patients,
      with infection the most frequent problem in nearly all of these patients (95%).
      Pneumonia was the leading complication associated patient survival. All patients
      who developed pneumonia as a late complication during a complicated postoperative
      course died postoperatively. The postoperative Goris score of the patients who
      died was 6.9 +/- 2.9 (range 3-11), whereas the surviving patients' score averaged
      2.2 +/- 1.9 (range 0-9), which was significantly different (p = 0.0003). None of
      the 54 patients with a GORIS score < or = 2 died postoperatively, whereas 5 of 6
      patients with a score > or = 9 died (p = 0.0001). Severe liver dysfunction rather
      than the extent of resection influences clinical mortality. Patients > 80 years
      of age with a preoperative severe liver dysfunction showed a postoperative
      mortality of 57%, and all of these patients developed postoperative
      complications. Therefore resection cannot be recommended for those patients.
      Cirrhosis led to an unacceptable mortality of 44% after hepatic resection of > or
      = 5 liver segments for primary neoplasia of the liver. Major resections cannot be
      recommended in the aged with gallbladder cancer because 50% of the patients died
      after such operations. Overall, only resection of > or = 5 liver segments with
      segments I to III or less remaining were found to pose a major risk for clinical
      mortality and morbidity, but the cause of death was preexisting liver dysfunction
      and cirrhosis in all of these patients. Major resections of large neoplasia of
      the liver can be recommended even in the aged, but a preoperative preselection of
      patients with respect to liver function and pulmonary function preoperatively may
      help lower the postoperative morbidity and mortality, especially in patients who
      will undergo resection of > or = 5 liver segments. Major hepatic resection for
      metastatic disease to the liver in the elderly carries no additional survival
      risk. Patients > 65 years of age and especially those > 80 years of age are more
      liable to succumb to postoperative organ failure and complications, especially
      infections.

PMID- 9523525
TI  - Palliative operation for cancer of the head of the pancreas: significance of
      pancreaticoduodenectomy and intraoperative radiation therapy for survival and
      quality of life.
AB  - The benefits of a palliative operation and intraoperative radiation therapy
      (IORT) for survival and quality of life (QOL) of patients with cancer of the head
      of the pancreas are not clear. Survival and hospital-free survival (HFS), which
      are considered to be objective indicators of QOL, were studied in 13 patients who
      underwent palliative pancreaticoduodenectomy (PD) and 32 patients who underwent
      surgical bypass. Although there was no significant difference in the survival of
      patients who underwent PD or bypass (median survivals of 9 months and 7 months,
      respectively), HFS for 3 months or longer was achieved in 84.6% of the patients
      who underwent PD, which was significantly higher than that of the 53.1% in
      patients who underwent surgical bypass (p < 0.05). Among TNM stage III patients,
      a significant difference in survival was observed between surgical bypass
      associated with IORT and bypass alone (p < 0.05); the median survival time of the
      IORT group was 10 months, whereas that of the control group was 5 months. In
      addition, HFS of 3 months or longer was achieved in 83.3% of patients who
      underwent bypass with IORT but in only 25.0% of the patients who underwent
      surgery alone (p < 0.01). The addition of IORT to palliative PD neither prolonged
      survival nor improved HFS. These results show the beneficial effect of palliative
      PD on QOL, and the efficacy of IORT for survival and QOL was proved in cases with
      stage III pancreatic cancer who underwent surgical bypass. For patients subjected
      to palliative PD, however, IORT is not thought to be beneficial for either
      survival or QOL.

PMID- 9523527
TI  - Splenectomy remains the therapeutic procedure of choice for SH.

PMID- 9523526
TI  - Adrenalectomy for primary aldosteronism: long-term follow-up study in 29
      patients.
AB  - Primary aldosteronism consists of a mixture of subgroups. The operative treatment
      is successful only in cases of aldosterone-producing neoplasia (and in rare cases
      of primary unilateral hyperplasia); all other cases should be treated medically.
      The aim of this study was to determine if aldosterone-producing neoplasia had
      been successfully differentiated from the other subgroups and the outcome of
      operative treatment. Altogether 29 patients with primary aldosteronism were
      operated on between January 1, 1979 and December 31, 1993. Patient charts were
      reviewed retrospectively. The follow-up data were collected from the patients'
      charts, and all patients were contacted to obtain recent blood pressure and serum
      potassium values. The patients were asked about symptoms related to
      hyperaldosteronism. If any suspicion of recidive aldosteronism was present,
      patients were carefully reexamined by hormonal tests and computed tomography
      (CT). A total of 27 patients had unilateral adenoma, 1 patient had hyperplasia,
      and 1 patient had an aldosterone-producing cortical carcinoma. There was no
      operative mortality or morbidity. The serum potassium level had normalized in all
      patients. Mean follow-up time was 76 months. One patient died during the follow
      up from cholangiocarcinoma; 11 patients (41%) were cured by the operation, 10
      patients (37%) have a mild but medicated hypertension, and in the remaining 22%
      the hypertension persisted but was well controlled by the medication. Of the 29
      patients, 28 were correctly diagnosed as having an aldosterone-producing
      neoplasm. Basic hormonal studies and CT can be used effectively to differentiate
      aldosterone-producing neoplasia from hyperplasia in most cases.

PMID- 9523528
TI  - Optical absorption of blood depends on temperature during a 0.5 ms laser pulse at
      586 nm.
AB  - Optical properties are important parameters in port wine stain laser treatment
      models. In this study we investigated whether changes in blood optical properties
      occur during a 0.5 ms laser pulse. Blood from three volunteers was irradiated in
      vitro with laser pulses (radiant exposure 2-12 J cm-2, wavelength 586 nm, pulse
      length 0.5 ms). Reflection and transmission coefficients, measured using double
      integrating spheres, decreased slightly during the first part of the pulse. At
      2.9 J cm-2 radiant exposure, the reflectance increased, independent of total
      radiant exposure of the pulse. This was caused by blood coagulation. A second
      sudden increase in reflection and a significant increase in transmission occurred
      near 6.3 J cm-2 and was accompanied by a "popping" sound, indicating rapid
      expansion of bubbles due to blood vaporization. A multilayered model of blood was
      used to fit calculated transmission coefficient curves to the measurements and
      determine temperature-dependent optical blood absorption. Heat diffusion was
      shown to be of minor importance. A 2.5-fold increase in absorption for
      temperatures increasing from 20 to 100 degrees C, accurately describes
      transmission coefficients measured up to 2.9 J cm-2.

PMID- 9523529
TI  - Control of NO concentration in solutions of nitrosothiol compounds by light.
AB  - We studied the thermal and photolytic decomposition of two S-nitrosothiols, S
      nitrosoglutathione (GSNO) and S-nitroso-N-acetylpenicillamine (SNAP), in water or
      propanol solutions. A "concentration clamp" (relatively constant concentration of
      NO as a function of time) could be implemented in a closed volume by varying the
      pH, concentration of nitrovasodilator and intensity of the light source.
      Depending on the conditions, the light either stimulated NO release or sharply
      decreased NO concentration in the test solutions. Changes in the absorption
      spectra of GSNO solutions were monitored as a function of light exposure.
      Generation of superoxide as a product of a photolytic decomposition reaction of S
      nitrosothiols and further oxidation of NO is the most likely mechanism for light
      suppression of NO concentration.

PMID- 9523530
TI  - Mutagenesis mediated by triple helix-forming oligonucleotides conjugated to
      psoralen: effects of linker arm length and sequence context.
AB  - Targeted mutagenesis and gene knock-out can be mediated by triple helix-forming
      oligonucleotides (TFO) linked to mutagenic agents, such as psoralen. However,
      this strategy is limited by the availability of homopurine/homopyrimidine
      stretches at or near the target site because such sequences are required for high
      affinity triplex formation. To overcome this limitation, we have tested TFO
      conjugated to psoralen via linker arms of lengths varying from 2 to 86 bonds,
      thereby designed to deliver the psoralen at varying distances from the third
      strand binding site present at the 3' end of the supFG1 mutation reporter gene.
      Following triplex formation and UVA irradiation, mutations were detected using an
      SV40-based shuttle vector assay in human cells. The frequency and distribution of
      mutations depended on the length of the linker arm. Precise targeting was
      observed only for linker arms of length 2 and 6, which also yielded the highest
      mutation frequencies (3 and 14%, respectively). Psoralen-TFO with longer tethers
      yielded mutations at multiple sites, with the maximum distance from the triplex
      site limited by the linker length but with the distribution within that range
      influenced by the propensity for psoralen intercalation at A:T base-pair-rich
      sites. Thus, gene modification can be extended beyond the site of third strand
      binding but with a decrease in the precision of the targeting.

PMID- 9523531
TI  - Regulation of stimulated cyclic AMP synthesis by urocanic acid.
AB  - Urocanic acid (UCA) has been shown to mediate the UVB radiation-induced
      immunosuppression initiated in the skin by UV-induced isomerization from the
      trans to the cis isomer. However, the mechanism by which cis-UCA acts is still
      unclear. Therefore, the present study was undertaken to determine the effect of
      trans- and cis-UCA on cyclic adenosine 3',5'-monophosphate (cAMP) synthesis in
      human dermal fibroblasts, Golden Syrian hamster hepatocytes and in the human
      adenocarcinoma cell line, HT29. Neither trans- nor cis-UCA was able to stimulate
      cAMP synthesis directly in any of the models tested. In human dermal fibroblasts,
      cis-UCA, in contrast to trans-UCA, specifically inhibited cAMP synthesis induced
      by either prostaglandin (PG) E1 or PGE2 with a maximum inhibitory effect of 25
      30% at cis-UCA concentrations greater than 1 microM and half-maximum inhibitory
      effect (EC50) observed at 35 nM. The effect of cis-UCA was not to stimulate
      phosphodiesterase and cAMP breakdown. The inhibitory effect of cis-UCA (an
      imidazole derivative) was not mediated through stimulation of the alpha 2
      adrenergic receptor. The inhibitory effect of cis-UCA on stimulated cAMP
      synthesis was a function of the cell density and was only significant when the
      fibroblasts were confluent or postconfluent. In contrast to the studies with
      human dermal fibroblasts, an inhibitory effect of cis-UCA was not observed in
      either isolated hamster hepatocytes or HT29 cells, in which cAMP synthesis was
      stimulated by glucagon and vasoactive intestinal peptide, respectively. These
      results point to a possible regulation of cAMP synthesis in fibroblasts as one
      mechanism by which cis-UCA exerts its biological effect in the skin.

PMID- 9523532
TI  - A comparative analysis of silicon phthalocyanine photosensitizers for in vivo
      photodynamic therapy of RIF-1 tumors in C3H mice.
AB  - Photofrin photodynamic therapy (PDT) has recently received FDA approval for the
      palliative treatment of totally and partially obstructing esophageal
      malignancies. However, there is a need for new PDT photosensitizers because
      Photofrin has a number of undesirable features. The purpose of this study was to
      evaluate the efficacy of four amine-bearing silicon phthalocyanines--Pc4, Pc10,
      Pc12 and Pc18--as potential PDT photosensitizers. Equimolar concentrations of
      these Pc were found to be highly effective at causing the regression of RIF-1
      tumors transplanted to C3H/HeN mice. The amount of Pc4 necessary to cause an
      equivalent amount of tumor regression in this model system was substantially less
      than the amount of Photofrin. The cutaneous phototoxicity of the silicon Pc
      photosensitizer was assessed by the utilization of the murine ear-swelling model.
      When C3H mice were exposed to 167 J/cm2 of polychromatic visible light from a UVB
      filtered solar simulator, which emitted UV radiation and visible light above 320
      nm, the Pc produced little, if any, cutaneous photosensitivity. These results
      indicate that Pc4, Pc10, Pc12 and Pc18 are at least as effective as Photofrin in
      PDT protocols, while at the same time addressing many of the drawbacks of
      Photofrin.

PMID- 9523533
TI  - Importance of the treatment field for the application of vascular photodynamic
      therapy to inhibit intimal hyperplasia.
AB  - Intimal hyperplasia (IH) plays a dominant role in the development of restenosis.
      In previous studies, photodynamic therapy (PDT) prevented IH induced by segmental
      balloon injury of the rat carotid. The critical elements required to control IH
      effectively with this technique are not fully understood. This study assessed the
      importance of the treatment field by studying the repair process of injured
      vessels, in which the PDT-treatment field did not target the entire injured area.
      The entire rat common carotid artery was balloon-injured to induce IH, whereas
      only the cervical segment below the bifurcation was subjected to PDT by external
      light irradiation after administration of the photosensitizer chloroaluminum
      sulfonated phthalocyanine. Light irradiation of injured arteries without
      photosensitizer served as control for PDT, and PDT of uninjured arteries was
      included as a control group for the balloon injury. Histologic characterization
      of the repair process was sequentially assessed. Balloon-injured arteries without
      PDT displayed rapid IH development with a peak at 2 weeks. Photodynamic therapy
      of balloon-injured arteries resulted in complete local depletion of medial smooth
      muscle cells (SMC), which was associated with a lack of IH until 2 weeks.
      However, at 4 and 16 weeks there was significant IH in PDT-treated arteries
      despite a lack of medial SMC repopulation. A wave of IH progression over the
      acellular media was observed in these arteries, migrating from the injured non
      PDT-treated area. The PDT of uninjured arteries did not result in IH and was also
      associated with a persistent acellular media. Delayed IH development after PDT of
      injured vessels can result from IH progression from an injured site not included
      in the treatment field. This also indicated that the source of cells developing
      the intimal hyperplasia lesion can originate from an area remote from the lesion.
      Together with previous results and the determination that PDT itself does not
      induce IH, it can be reasoned that inclusion of the whole injured artery or a
      section of an uninjured margin in the treatment field is essential for effective
      PDT prevention of IH.

PMID- 9523534
TI  - Factors affecting virus photoinactivation by a series of phenothiazine dyes.
AB  - A series of four phenothiazine dyes, including methylene blue (MB), were
      previously tested for their ability to photoinactivate viruses in red cell
      suspensions. One of the dyes, 1,9-dimethyl-3-dimethylamino-7
      dimethylaminophenothiazine (1,9-dimethylmethylene blue), exhibited good
      intracellular and extracellular virucidal activity for several RNA and DNA
      viruses under conditions that minimally affected red cell properties. In order to
      understand why the virucidal specificity of 1,9-dimethylmethylene blue was
      greater than other phenothiazines tested, the physical and chemical properties of
      the dye were compared to three other closely related analogues (MB, 1,9-dimethyl
      3-diethylamino-7-dibutylaminophenothiazine [compound 4-140], 1,9-dimethyl-3
      dimethylamino-7-diethylaminophenothiazine [compound 6-136]). All compounds
      required light and oxygen for virucidal activity and had relatively high singlet
      oxygen yields (> 0.5), but 1,9-dimethylmethylene blue had a singlet oxygen yield
      approximately 50% greater than that of MB. In addition, the
      hydrophobicity/hydophilicity of the compounds varied, with the partition
      coefficients (2-octanol : water) ranging from 0.11 for MB to 3560 for compound 4
      140. The dyes had the following affinities for DNA: 1,9-dimethylmethylene blue >
      compound 6-136 > MB approximately compound 4-140. This order was similar to the
      order of activities for photoinactivation of the nonenveloped bacteriophage, R17,
      by the four compounds. Results with the most hydrophobic compound, 4-140,
      contrasted with those obtained with 1,9-dimethylmethylene blue. Compound 4-140
      had a high affinity for protein and a low affinity for DNA. Although compound 4
      140 and light inactivated the nonenveloped bacteriophage R17 poorly, the dye
      readily photoinactivated enveloped viruses in buffer. However, unlike results
      with 1,9-dimethylmethylene blue, viral inactivation of enveloped viruses by
      compound 4-140 was completely inhibited by the presence of red cells and plasma.
      Thus, the high affinity of 1,9-dimethylmethylene blue for DNA and the dye's
      efficient singlet oxygen yield suggest viral nucleic acid as a potential target,
      which could explain the photosensitizer's ability to inactivate viruses without
      adversely affecting anucleate red cells.

PMID- 9523535
TI  - Potential mechanisms of photodynamic inactivation of virus by methylene blue. I.
      RNA-protein crosslinks and other oxidative lesions in Q beta bacteriophage.
AB  - A spectrum of oxidative lesions was observed in a bacteriophage-based model
      system that is very sensitive to the photodynamic activity of selected dyes. When
      suspensions of the intact bacteriophage Q beta were exposed to methylene blue
      plus light (MB + L), inactivating events, or "hits" occurred that were oxygen
      dependent and that were associated with the formation of several specific
      lesions: (1) carbonyl moieties on proteins, (2) 8-oxo-7,8-dihydroguanine (8
      oxoGua), and (3) single-strand breaks (ssb) in the RNA genome and (4) RNA-protein
      crosslinks. Formation of carbonyl groups associated with protein in the Q beta
      phage preparation correlated positively with photoinactivation of the phage with
      increasing doses of either of the sensitizers MB or rose bengal. Strand breaks in
      the Q beta genomic RNA were observable at high MB concentrations but appeared not
      to be significant at the lower concentrations of MB, as full-length Q beta RNA
      was observable well beyond the 99% inactivation point in MB dosage. It was shown
      that the number of 8-oxoGua lesions were unlikely to be sufficient to account for
      the number of lethal events. Following exposure to MB + L, crosslink formation
      between Q beta RNA and protein was observed by virtue of the location of RNA at
      the interface of phenol-aqueous extractions of phage suspensions. A significant
      increase over background of RNA-protein complexes (including full-length Q beta
      RNA) was observed at the lowest concentration of MB tested (0.5 microM), which
      corresponded roughly to an average of 2 lethal hits per phage or approximately
      13% survival compared to the zero MB control (100% survival). Due to its close
      correlation with Q beta inactivation and its expected lethality, RNA-protein
      crosslink formation may be important as an inactivating lesion in bacteriophage Q
      beta following MB + L exposure.

PMID- 9523536
TI  - Photodynamic treatment with benzoporphyrin derivative monoacid ring A produces
      protein tyrosine phosphorylation events and DNA fragmentation in murine P815
      cells.
AB  - Treatment with benozopophyrin derivative monoacid ring A (BPD-MA, verteporfin)
      and broad-spectrum fluorescent light rapidly produced apoptosis in murine P815
      mastocytoma cells. Fragmentation of DNA, a fundamental characteristic of cells
      undergoing apoptosis, was evident within 3 h following the photodynamic
      treatment. Western immunoblot analysis using the specific antiphosphotyrosine
      monoclonal antibody 4G10 indicated that molecular species of > 200 kDa were
      phosphorylated on tyrosine residues during or immediately following the
      irradiation of cells loaded with BPD-MA. Increased tyrosine phosphorylation of a
      15 kDa protein was evident by 15 min postirradiation. In the absence of light,
      BPD-MA did not affect the status of cellular protein tyrosine phosphorylation or
      cause DNA fragmentation. The protein kinase inhibitor staurosporine prevented
      tyrosine phosphorylation of the > 200 kDa species but did not affect tyrosine
      phosphorylation of the 15 kDa protein or the level of DNA fragmentation produced
      by the photodynamic treatment. The protein tyrosine phosphorylation events
      observed for P815 cells treated with cytotoxic levels of BPD-MA and light may not
      be directly related to the induction of the apoptotic cell death pathway.

PMID- 9523537
TI  - Selective examination of plasma membrane-associated photosensitizers using total
      internal reflection fluorescence spectroscopy: correlation between photobleaching
      and photodynamic efficacy of protoporphyrin IX.
AB  - Fluorescence spectra, fluorescence decay kinetics, photobleaching kinetics and
      photodynamic efficacy of protoporphyrin IX (PP) were investigated in endothelial
      cells in vitro after different incubation times. Fluorescence spectra and
      photobleaching kinetics were determined during total internal reflection (TIR)
      illumination or epi-illumination. Because penetration depth of the excitation
      light during TIR illumination was limited to about 100 nm, plasma membrane
      associated PP was almost selectively examined. Spectra obtained by TIR
      fluorescence spectroscopy (FS) showed a very low background, whereas spectra
      obtained by epi-illumination exhibited considerable background by
      autofluorescence and scattered light. For photobleaching kinetics during TIR
      illumination after 1 h or 24 h incubation, a biexponential fluorescence decrease
      was observed with a rapidly and a slowly bleaching portion. After 1 h incubation,
      the rapidly bleaching portion was the predominant fraction, whereas after 24 h
      incubation comparable relative amounts of the rapidly and slowly bleaching
      portion were determined. The rapidly and slowly bleaching portion were assigned
      to PP monomers and aggregated species in close vicinity to the plasma membrane.
      Fluorescence decay measurements after epi-illumination support the decrease of PP
      monomers within the whole cell with increasing incubation time. In contrast to
      TIR illumination, photobleaching of PP during epi-illumination was characterized
      by slow monoexponential fluorescence decrease after 1 h or 24 h incubation.
      Photodynamic efficacy of PP using epi-illumination was found to depend strongly
      on incubation time. Considerable cell inactivation was determined for short
      incubation times (1 h or 3 h), whereas photodynamic efficacy was diminished for
      longer incubation times. Reduced photodynamic efficacy after long incubation
      times was assigned to the lower amount of photodynamically active monomers
      determined close to the plasma membrane as well as within the whole cell. In
      conclusion, TIRFS measurements are suggested to be an appropriate tool for the
      examination of the plasma membrane-associated photosensitizer fraction in living
      cells.

PMID- 9523538
TI  - Reliability study of the Leg-O-Meter, an improved tape measure device, in
      patients with chronic venous insufficiency of the leg. VEINES Group.(Venous
      Insufficiency Epidemiologic and Economic Study).
AB  - The objective of this study was to evaluate the inter-rater reliability of the
      Leg-O-Meter, an instrument designed to measure the ankle or calf circumference.
      The Leg-O-Meter consists of a tape measure fixed to a stand attached to a small
      board on which the patient is in standing position. For this study the tape
      measure of the Leg-O-Meter was fixed at 10 cm from the board in order to
      standardize all measurements. Informed consent to participate in the study was
      obtained from 39 patients consulting the phlebology clinic of Hopital St-Michel,
      Paris, France. Participants were asked to enter a closed room where four
      independent and blinded observers consecutively took measurements of both legs
      with the Leg-O-Meter. The order of the observers was randomized between patients.
      Under the assumption of a two-way random effects model an intraclass correlation
      coefficient (ICC) was used to determine the reliability or reproducibility of a
      measure with the Leg-O-Meter. The overall reliability coefficient calculated by
      the ICC for the right and left leg were estimated at 97.09% [95.52%;100%]95% and
      97.08% [95.86%;100%]95%, respectively. The authors conclude that the Leg-O-Meter
      gives a standardized and reliable measure of the circumference of the ankle.
      Furthermore, it is not invasive or costly.

PMID- 9523539
TI  - LDL apheresis for arteriosclerosis obliterans with occluded bypass graft: change
      in prostacyclin and effect on ischemic symptoms.
AB  - To study the mechanism of efficacy of low-density lipoprotein (LDL) adsorption
      for arteriosclerosis obliterans (ASO), eight ASO patients without indication for
      bypass surgery underwent LDL apheresis twice a week for 5 weeks and the change in
      prostaglandin 12 (PGI2) and thromboxane A2 (TXA2) due to LDL apheresis was
      measured. The concentration of 6-keto-PGF1alpha, a metabolite of PGI2, in
      systemic venous blood significantly increased from 10.4 +/- 1.8 to 42.0 +/- 10.6
      pg/mL (P<0.05) after one session of LDL apheresis, while no significant change of
      TXB2, a metabolite of TXA2, was encountered. The ratio of 6-keto-PGF1alpha/TXB2
      also rose dramatically from 0.213 +/- 0.044 to 0.522 +/- 0.128 (P<0.05). In five
      patients, the ischemic clinical symptoms improved and both the concentration of 6
      keto-PGF1alpha and the ratio of 6-keto-PGF1alpha/TXB2 increased significantly,
      whereas in three patients there was no effect on clinical symptoms and neither
      parameter changed. These results suggest that elevated production of PGI2 from
      vascular cells due to LDL apheresis might contribute to improvement of ischemic
      symptoms.

PMID- 9523540
TI  - Preservation of skin vasoconstrictor responses in chronic atherosclerotic
      peripheral vascular disease.
AB  - Peripheral neuropathy is often found in ischemic limbs with nondiabetic
      atherosclerotic peripheral vascular disease (PVD). Sensory symptoms such as
      burning pain are common in severely ischemic limbs, and sympathectomy has been
      undertaken for ischemic rest pain. The authors assessed noninvasive quantitative
      skin vasomotor reflexes in toes and standard systemic cardiovascular autonomic
      tests in 44 PVD subjects with varying severity of limb ischemia, 30 age-matched
      control subjects, and nine PVD subjects associated with diabetes. Skin
      vasoconstrictor reflexes to inspiratory gasp, Valsalva maneuver, and postural
      change, and the postischemic reactive hyperemic response, were evaluated by the
      measurement of skin blood flow on toe pads by use of a laser Doppler flowmeter.
      Vasoconstrictor responses were not significantly different between PVD toes, even
      in severely ischemic limb, and age-matched controls. Reactive hyperemia was
      significantly less in PVD than in controls. Cardiovagal and systemic
      vasoconstrictor reflexes were also evaluated. All PVD subjects showed normal
      systemic cardiovascular reflexes. In contrast, these reflexes were severely
      impaired in diabetic PVD. The authors demonstrated that skin vasoconstrictive
      sympathetic reflex is preserved in chronically ischemic limbs with PVD,
      suggesting that sympathetic nerve fibers are relatively resistant to chronic
      ischemia.

PMID- 9523541
TI  - Association of subclavian and jugular vein thrombosis: color doppler sonographic
      evaluation.
AB  - In case of clinical symptoms of subclavian vein thrombosis a phlebographic or
      color Doppler sonographic investigation should be performed. Phlebography is a
      sensitive method to exclude the thrombosis in the subclavian vein but not in the
      jugular vein. Color Doppler sonography additionally gives information about the
      surrounding tissue and the jugular vein. The authors analyze their color Doppler
      sonographic data, first, to evaluate the association of internal jugular and
      subclavian vein thrombosis and, second, to demonstrate the necessity for a color
      Doppler investigation. Of 213 patients who suffered from a thrombosis, 93 had a
      subclavian vein thrombosis, 64 had a combined thrombosis in the internal jugular
      and subclavian vein, and 56 had an isolated internal jugular vein thrombosis.
      There is a high association between subclavian and internal jugular vein
      thrombosis, and a color Doppler investigation of both the subclavian and internal
      jugular veins is necessary.

PMID- 9523542
TI  - Plasma leukocyte elastase concentration and coronary artery disease.
AB  - It has previously been shown that leukocyte elastase is involved in the
      pathogenesis of atherosclerosis. Few studies have addressed the relation between
      leukocyte elastase concentrations and coronary artery disease (CAD). The authors
      investigated (1) the clinical significance of leukocyte elastase determination in
      the diagnosis of CAD and (2) the relation between plasma leukocyte elastase
      concentration and lesion morphology. The study included 185 subjects (140 men, 45
      women) who underwent coronary angiography during investigation of chest pain; 135
      had coronary stenosis (Group I) and 50 had nonstenotic coronaries (Group II).
      Among Group I patients, those with simple atheromatous plaques were distinguished
      from those with complex plaques. Elastase concentrations in Group I were greater
      than in Group II (57.1 +/- 1.16 micrograms I[-1] vs 27.6 +/- 1.0 microgram, I[
      1], P<0.001), and greater in complex plaque patients than in those with simple
      plaques (64.5 +/- 1.24 micrograms I[-1] vs 45.9 +/- 1.01 micrograms I[-1],
      P<0.001). Logistic regression analysis showed (1) that elastase concentration,
      age, and sex had independent value for prediction of CAD and (2) that among Group
      I patients, the risk of complex plaques was greatest for those with high elastase
      concentration. These results suggest that plasma leukocyte elastase concentration
      is a sensitive diagnostic marker of CAD and that high values of elastase may
      indicate the presence of complex atheromatous plaques.

PMID- 9523543
TI  - Evaluation of polarographic measurements of basal muscle oxygen tension in type I
      diabetic patients.
AB  - Microcirculatory changes occur early in insulin-dependent diabetes mellitus
      (IDDM) and are believed to be an early feature of late diabetic complications,
      leading to reduced oxygen pressure and hypoxia in the skin and other tissues.
      Whether muscle oxygen supply is also altered is unknown. Therefore, the authors
      analyzed polarographic measurements of muscle oxygen tension in 44 healthy type I
      diabetic patients (mean age 28 years; mean diabetes duration 7 years) and in 57
      healthy controls, matched for age, sex, and body mass index, and the
      corresponding influencing factors. Two measurements were taken at rest 60 minutes
      apart in the anterior tibial muscle. Muscle oxygen tensions did not differ
      between IDDM patients and controls (23.0 +/- 8.6 vs 25.3 +/- 9.0 mmHg) and were
      reproducible on repeated measurements (25.3 +/- 9.7 vs 25.5 +/- 7.4 mmHg).
      Coefficients of variation were 13.5 +/- 10.8% in IDDM patients and 13.1 +/- 9.3%
      in controls. Compared with controls, in IDDM patients hemoglobin A1c (HbA1c) and
      blood glucose concentrations were elevated, and arterial oxygen pressure was
      significantly lower. Muscle oxygen tensions were positively correlated with blood
      glucose concentrations in IDDM patients (Rho=0.48, P=0.002) but not with HbA1c or
      with insulin concentrations. The authors conclude that the polarographic
      measurement of muscle oxygen tension is a reliable method with good
      reproducibility. Hypoxia in the anterior tibial muscle of type I diabetic
      patients can be excluded. In IDDM patients the level of muscle oxygen tension is
      correlated with the level of blood glucose concentration.

PMID- 9523544
TI  - Suppressive effect of simvastatin on intramural small coronary arterial lesions
      in cholesterol-fed rabbits.
AB  - The aim of this study was to examine the suppressive effect of simvastatin on
      intramural coronary arterial lesions in cholesterol-fed rabbits. In one
      experiment, six groups of rabbits were fed laboratory chow alone or with added
      0.1%, 0.2%, 0.3%, 0.5% or 1.0% cholesterol for 16 weeks. In another experiment,
      four groups of rabbits were fed a 0.5% cholesterol diet and treated with
      simvastatin at 1, 3, or 5 mg/kg/day or placebo. In each rabbit, the levels of
      serum total cholesterol (TC) were determined at 1-week intervals to calculate the
      integrated values. The lesion induction ratio was defined as the ratio of
      intramural coronary arteries 50-150 microm in diameter with arterial lipoidosis
      to the total number of arteries of the same diameter. In the two experiments,
      there were positive correlations between the lesion induction ratio and
      integrated TC (r=0.785, P<0.0001 and r=0.763, P<0.0001, respectively). The slopes
      of the regression lines for integrated TC obtained in the two experiments were
      similar, but the lesion induction ratio in the simvastatin-treated group was
      always lower, by about 14%, in comparison with that in the non-simvastatin
      treated group. These findings suggest that simvastatin induces lesion reduction
      not only by reducing the levels of circulating cholesterol but also by directly
      suppressing the development of lipoidosis.

PMID- 9523545
TI  - Cocaine-induced peripheral vascular occlusive disease--a case report.
AB  - Two patients with cocaine-induced peripheral vascular occlusive disease are
      presented. A 37-year-old man was admitted to the hospital for evaluation of
      severe pain and numbness of his feet. He had used cocaine prior to admission.
      Arteriography showed bilateral occlusions of superficial femoral, popliteal, and
      trifucation arteries. Despite repeated infusions of urokinase, he developed
      progressive bilateral gangrene of both legs necessitating bilateral below-knee
      amputations. The second patient developed similar symptoms after smoking cocaine.
      Arteriography showed vasospasm bilaterally from the iliac arteries distally. I.v.
      nitroglycerin infusion caused resolution of the vasospasm and ischemic symptoms.

PMID- 9523546
TI  - Pseudoaneurysm of the descending thoracic aorta following Streptococcus
      pneumoniae bacteremia--a case report.
AB  - Reported here is the case of an 82-year-old man with underlying atherosclerotic
      vascular disease who developed an aortic pseudoaneurysm following Streptococcus
      pneumoniae bacteremia. The patient experienced severe midthoracic back pain in
      association with fever, chills, leukocytosis, and an elevated erythrocyte
      sedimentation rate. Computed tomography revealed a pseudoaneurysm of the
      descending thoracic aorta with displacement of intimal calcification, which was
      likely due to infection and subsequent ulceration of an atherosclerotic plaque
      from preceding S. pneumoniae bacteremia. The patient declined surgical
      intervention and, despite antibiotic therapy, died shortly after presentation.

PMID- 9523547
TI  - Aortic valve stenosis as a cause of major systemic embolism--a case report.
AB  - This is the first documented case of a patient suffering from embolic occlusion
      of the left brachial artery caused by a large embolus growing on a lesion of a
      stenosed calcified aortic valve. Supported by their own additional observations
      the authors suggest that severe calcified aortic valve stenosis should be
      considered as an indication for anticoagulation in the period before surgical
      valve replacement.

PMID- 9523548
TI  - Anomalous course of the common carotid arteries: CT and MRA illustration--a case
      report.
AB  - Recognition of normal vascular variations is tantamount to accurate diagnosis and
      intervention. The authors describe an unusual course for the common carotid
      arteries that was incidentally identified on routine cervical spine x-ray films.
      The embryonic events leading to this normal variant are reviewed.

PMID- 9523549
TI  - GM1 ganglioside: in vivo and in vitro trophic actions on central neurotransmitter
      systems.
AB  - There is now substantial evidence that GM1 ganglioside is effective in partially
      correcting the consequences of neuroinjury in a number of in vivo and in vitro
      model systems. Although the molecular mechanism(s) and the substrates for the
      neurotrophic activity of the gangliosides are not fully understood, the published
      experimental work suggests that GM1 has antineurotoxic, neuroprotective, and
      neurorestorative effects on various central neurotransmitter systems. This review
      focuses attention on studies reporting that GM1 restores neuronal integrity and
      function in the brain of lesioned young as well as aged animals. Critical
      analysis of these studies can provide guidance for future ganglioside research
      and may point to novel approaches for treating neuroinjury and a variety of
      degenerative conditions, including aging.

PMID- 9523550
TI  - Splicing of a regulated exon reveals additional complexity in the axonal
      microtubule-associated protein tau.
AB  - Tau is a microtubule-associated protein whose transcript undergoes complex
      regulated splicing in the mammalian nervous system. Exon 6 of the gene is an
      alternatively spliced cassette whose expression pattern and splicing regulation
      had not been previously analyzed in the human. The expression profile of exon 6
      is completely different from that of the better-analyzed exons 2, 3, 4A, and 10,
      implying the utilization of distinct regulatory factors. The default splicing
      behavior of the exon had demonstrated the existence of what were initially
      considered cryptic splice sites. However, analysis of the expression pattern of
      exon 6 suggests that these splice sites are utilized in certain human tissues
      and, if translated, would result in a radically altered tau protein. Lastly,
      expression of exon 6 minigene constructs in cells indicates that its flanking
      exons are involved in its inclusion and in the modulation of the ratio of its
      variants.

PMID- 9523551
TI  - A novel orphan G protein-coupled receptor primarily expressed in the brain is
      localized on human chromosomal band 2q21.
AB  - A human hippocampus cDNA library was screened with a probe obtained from
      degenerate RT-PCR aimed at P2Y-homologous sequences. A positive clone, designated
      hip4, was identified containing an open reading frame of 1,020 bp that had been
      previously detected in a published genomic clone called R12. Subsequent screening
      of a human fetal brain cDNA library yielded a splice variant with a 1,104-bp open
      reading frame, which was named fb1. Both variants display the seven-transmembrane
      topology that is typical for G protein-coupled receptors. Probing a human
      multitissue northern blot revealed two brain-specific transcripts of 2.3 and 6.3
      kb, respectively. Northern blot analyses with specific fragments confirmed that
      the two transcripts are generated by alternative polyadenylation yielding two
      different 3' untranslated regions. A genomic clone from the corresponding gene
      was isolated and mapped to human chromosomal band 2q21 by fluorescence in situ
      hybridization.

PMID- 9523552
TI  - Distribution of mRNAs encoding the peroxisome proliferator-activated receptor
      alpha, beta, and gamma and the retinoid X receptor alpha, beta, and gamma in rat
      central nervous system.
AB  - We report the isolation, by RT-PCR, of partial cDNAs encoding the rat peroxisome
      proliferator-activated receptor (PPAR) isoforms PPAR alpha, PPAR beta, and PPAR
      gamma and the rat retinoid X receptor (RXR) isoforms RXR alpha, RXR beta, and RXR
      gamma. These cDNAs were used to generate antisense RNA probes to permit analysis,
      by the highly sensitive and discriminatory RNase protection assay, of the
      corresponding mRNAs in rat brain regions during development. PPAR alpha, PPAR
      beta, RXR alpha, and RXR beta mRNAs are ubiquitously present in different brain
      regions during development, PPAR gamma mRNA is essentially undetectable, and RXR
      gamma mRNA is principally localised to cortex. We demonstrate, for the first
      time, the presence of PPAR and RXR mRNAs in primary cultures of neonatal
      meningeal fibroblasts, cerebellar granule neurons (CGNs), and cortical and
      cerebellar astrocytes and in primary cultures of adult cortical astrocytes. PPAR
      alpha, PPAR beta, RXR alpha, and RXR beta mRNAs are present in all cell types,
      albeit that PPAR alpha and RXR alpha mRNAs are at levels near the limit of
      detection in CGNs. PPAR gamma mRNA is expressed at low levels in most cell types
      but is present at levels similar to those of PPAR alpha mRNA in adult astrocytes.
      RXR gamma mRNA is present either at low levels, or below the level of detection
      of the assay, for all cell types studied.

PMID- 9523553
TI  - Cyclic AMP protects against staurosporine and wortmannin-induced apoptosis and
      opioid-enhanced apoptosis in both embryonic and immortalized (F-11kappa7)
      neurons.
AB  - The mechanism by which opiates affect fetal development is unknown, but one
      potential target is the programmed cell death (apoptosis) pathway of neurons.
      Apoptosis was induced in both primary neuronal cultures from embryonic day 7
      cerebral hemispheres of chick brain (E7CH) and the F-11kappa7 cell line (an
      immortalized mouse neuroblastoma x dorsal root ganglion hybrid stably transfected
      to overexpress kappa-opioid receptors) by either staurosporine or the
      phosphatidylinositol 3-kinase inhibitors wortmannin and LY294002. Cells
      pretreated with either the mu-specific opioid agonist morphiceptin (E7CH) or the
      kappa-specific opioid agonist U69,593 (F-11kappa7) for 24 h showed increased
      apoptosis in response to staurosporine or wortmannin when compared with non
      pretreated cells. The effects of morphiceptin and U69,593 were time- and dose
      dependent and antagonist-reversible, suggesting that they were receptor-mediated.
      Neither morphiceptin nor U69,593 by themselves had any measurable effect on cell
      viability or DNA fragmentation, and coaddition of opiates at the same time as
      staurosporine, wortmannin, or LY294002 did not enhance apoptosis. Time course
      studies indicated a maximal opioid effect at a time (16-24 h) when inhibition of
      adenylate cyclase had been maximal for many hours. Addition of dibutyryl cyclic
      AMP either before or at the time of opioid addition protected against apoptosis
      and reduced fragmentation to levels seen for staurosporine plus dibutyryl cyclic
      AMP alone. The specificity for cyclic AMP was confirmed by showing protection
      with the specific agonist Sp-adenosine 3',5'-cyclic monophosphothioate and
      increased killing with the antagonist Rp-adenosine 3',5'-cyclic
      monophosphothioate. We conclude that the opioid enhancement of apoptosis is based
      on the inhibition of adenylate cyclase and that the effect is time-dependent.

PMID- 9523554
TI  - Characterization of two distinct monoclonal antibodies specific for glial cell
      line-derived neurotrophic factor.
AB  - Here we report the generation and characterization of two distinct monoclonal
      antibodies, G-90 and B-1531, specific to glial cell line-derived neurotrophic
      factor (GDNF). ELISA results confirmed that G-90 and B-1531 both recognize GDNF.
      Western blots showed that G-90 recognized only the GDNF dimer, whereas B-1531
      recognized both the monomer and dimer. Peptide competition ELISA (PCE) and
      BIAcore data suggested that G-90 and B-1531 recognize different epitopes: PCE
      confirmed that B-1531 binds to NH2-terminal peptides between amino acids 18 and
      37, whereas G-90 does not; BIAcore data showed that B-1531 binds to the NH2
      terminus of GDNF, whereas G-90 does not. G-90, in a concentration-dependent
      manner, completely neutralized the GDNF-induced increases of choline
      acetyltransferase in cultured motoneuron and of dopamine uptake and morphological
      differentiation in dopaminergic neuron cultures. B-1531 had no neutralizing
      effects. GDNF-induced Ret autophosphorylation in NGR-38 cells was completely
      neutralized by G-90, whereas B-1531 had a moderate effect. These data show that G
      90 and B-1531 are specific antibodies to GDNF. The data also suggest that the NH2
      terminus of GDNF is not critical for activity. Partial inhibition of Ret
      phosphorylation is insufficient to down-regulate GDNF-induced biological
      activity.

PMID- 9523555
TI  - Cytotoxic effect of beta-amyloid on a human differentiated neuron is not mediated
      by cytoplasmic Ca2+ accumulation.
AB  - The effects of synthetic beta-amyloid (A beta1-42) on cell viability and cellular
      Ca2+ homeostasis have been studied in the human neuron-like NT2N cell, which
      differentiates from a teratocarcinoma cell line, NTera2/C1.D1, by retinoic acid
      treatment. NT2N viability was measured using morphological criteria and
      fluorescent live/dead staining and quantified using 3-(4,5-dimethylthiazol-2-yl)
      2,5-diphenyltetrazolium bromide metabolism. A beta1-42 dose-dependently caused
      NT2N cell death when it was present in the cell culture for 14 days but had no
      effect on viability when it was present for 4 days. The lowest effective
      concentration was 4 microM, and the strongest effect was produced by 40 microM.
      Control NT2N cells produced spontaneous cytosolic Ca2+ oscillations under basal
      conditions. These oscillations were inhibited dose-dependently (0.4-40 microM) by
      A beta1-42 that was present in the cell culture for 1 or 4 days. Ca2+ wave
      frequency was decreased from 0.21 +/- 0.02 to 0.05 +/- 0.02/min, amplitude from
      88 +/- 8 to 13 +/- 4 nM, and average Ca2+ level from 130 +/- 8 to 58 +/- 3 nM.
      The Ca2+ responses to 30 mM K+ and 100 microM glutamate were not different
      between control and A beta-treated cells. Thus, the results do not support the
      hypothesis that cytosolic early Ca2+ accumulation mediates A beta-induced NT2N
      cell death.

PMID- 9523556
TI  - Apoptosis of central and peripheral neurons can be prevented with cyclin
      dependent kinase/mitogen-activated protein kinase inhibitors.
AB  - Previous studies have indicated that certain members of the cyclin-dependent
      kinase/mitogen-activated protein kinase superfamily are involved in apoptosis of
      neuronal cells. Here, we have examined programmed cell death induced by
      withdrawal of neurotrophic support from CNS (rat retinal) and PNS (chick
      sympathetic, sensory, and ciliary) neurons. All four neuron types were equally
      rescued by the purine analogues olomoucine and roscovitine. Olomoucine inhibits
      multiple cyclin-dependent and mitogen-activated protein kinases with similar
      potency. Roscovitine is a more selective cyclin-dependent kinase inhibitor; but,
      so is butyrolactone I, which did not prevent retinal ganglion cell death. The
      specific p38MAPK inhibitor SB-203580 did not prevent apoptosis in retinal
      ganglion cells. Death of these cells in the absence of neurotrophic factors was
      accompanied by morphological changes indicative of apoptosis, including nuclear
      condensation and fragmentation. Treatment with olomoucine or roscovitine not only
      prevented these apoptotic changes in retinal ganglion cells but also blocked
      neurite outgrowth. The survival-promoting activity of olomoucine correlated with
      its in vitro IC50 for c-Jun N-terminal kinase-1 and its potency to repress c-jun
      induction in live PC12 cells. Roscovitine was more potent in rescuing neurons
      than in inhibiting Jun kinase. Thus, the antiapoptotic action of roscovitine
      might be due to inhibition of additional kinases.

PMID- 9523557
TI  - Collaborative and reciprocal effects of ciliary neurotrophic factor and nerve
      growth factor on the neuronal phenotype of human neuroblastoma cells.
AB  - We have probed the molecular basis of functional effects of ciliary neurotrophic
      factor (CNTF) and nerve growth factor (NGF) on aspects of the neuronal
      differentiation of LA-N-2 neuroblastoma cells. The influence of CNTF on the
      cholinergic phenotype can be accounted for by transcriptional/translational
      effects without implicating posttranslational mechanisms. Although both NGF
      receptors are expressed constitutively by LA-N-2 cells, CNTF has a marked
      stimulatory effect on trkA mRNA and protein. The NGF receptors are functional in
      serum-free conditions where they mitigate CNTF effects on cell adhesion but do
      not support process extension. Following priming by CNTF, NGF and CNTF have
      synergistic influences on process formation but not on choline acetyltransferase
      specific activity.

PMID- 9523558
TI  - Role of oxidative stress and the glutathione system in loss of dopamine neurons
      due to impairment of energy metabolism.
AB  - Alterations in the glutathione system and impairment in energy metabolism have
      both been implicated in the loss of dopamine neurons in Parkinson's disease. This
      study examined the importance of cellular glutathione and the involvement of
      oxidative stress in the loss of mesencephalic dopamine and GABA neurons due to
      inhibition of energy metabolism with malonate, the reversible, competitive
      inhibitor of succinate dehydrogenase. Consistent with previous findings, exposure
      to malonate for 24 h followed by 48 h of recovery caused a dose-dependent loss of
      the dopamine population with little effect on the GABA population. Toxicity was
      assessed by simultaneous measurement of the high-affinity uptake of [3H]dopamine
      and [14C]GABA. Total glutathione content in rat mesencephalic cultures was
      decreased by 65% with a 24-h pretreatment with 10 microM buthionine sulfoxamine.
      This reduction in glutathione level greatly potentiated damage to both the
      dopamine and GABA populations and removed the differential susceptibility between
      the two populations in response to malonate. These findings point to a role for
      oxidative stress occurring during energy impairment by malonate. Consistent with
      this, several spin-trapping agents, alpha-phenyl-tert-butyl nitrone and two
      cyclic nitrones, MDL 101,002 and MDL 102,832, completely prevented malonate
      induced damage to the dopamine neurons in the absence of buthionine sulfoxamine.
      The spin-trapping agents also completely prevented toxicity to both the dopamine
      and GABA populations when cultures were exposed to malonate after pretreatment
      with buthionine sulfoxamine to reduce glutathione levels. Counts of tyrosine
      hydroxylase-positive neurons verified enhancement of cell loss by buthionine
      sulfoxamine plus malonate and protection against cell loss by the spin-trapping
      agents. NMDA receptors have also been shown to play a role in malonate-induced
      dopamine cell loss and are associated with the generation of free radicals.
      Consistent with this, toxicity to the dopamine neurons due to a 1-h exposure to
      50 microM glutamate was attenuated by the nitrone spin traps. These findings
      provide evidence for an oxidative challenge occurring during inhibition of energy
      metabolism by malonate and show that glutathione is an important neuroprotectant
      for midbrain neurons during situations when energy metabolism is impaired.

PMID- 9523559
TI  - Continuous activation of pituitary adenylate cyclase-activating polypeptide
      receptors elicits antipodal effects on cyclic AMP and inositol phospholipid
      signaling pathways in CATH.a cells: role of protein synthesis and protein
      kinases.
AB  - Continuous exposure of cells to agonists develops a process that determines the
      extent to which the cells eventually respond to further stimuli. Here we used
      CATH.a cells (a catecholaminergic neuron-like cell line), which express pituitary
      adenylate cyclase-activating polypeptide (PACAP) receptors linked to both
      adenylyl cyclase and phospholipase C-beta pathways, to investigate the influence
      of prolonged hormonal treatment on dual signaling and gene transcription.
      Prolonged incubation of cells with PACAP failed to down-regulate the density and
      affinity of membrane binding sites and caused opposite changes in messenger
      systems: PACAP-stimulated cyclic AMP accumulation was attenuated in a time- and
      dose-dependent fashion (t(1/2) = 6.7 h and IC50 = 0.1 nM), whereas
      phosphoinositide turnover was overstimulated. Both effects were insensitive to
      pertussis toxin, whereas the drop in cyclic AMP concentration was also unchanged
      in the presence of 3-isobutyl-1-methylxanthine, indicating that neither Gi-like
      proteins nor cyclic nucleotide phosphodiesterases play a critical role in these
      processes. Blockade of protein synthesis with cycloheximide, as well as
      inhibition by H89 of cyclic AMP-dependent protein kinase (but not by
      bisindolylmaleimide of protein kinase C) antagonized the influences exerted by
      PACAP on adenylyl cyclase activity and inositol phosphate formation.
      Transcription of the chimeric GAL4-CREB construct, transiently transfected into
      CATH.a cells, was stimulated by PACAP, and this effect was potentiated as a
      result of chronic PACAP treatment. The results of the present investigation
      provide new insight into the possible differential regulation and cross-talks of
      transduction signals of receptors linked to multiplex signaling. They demonstrate
      that prolonged exposure of CATH.a cells to PACAP results in the desensitization
      of the cyclic AMP pathway and superinduction of the inositol phosphate signal,
      through protein neosynthesis and cyclic AMP-dependent protein kinase activation.
      At the same time, they show that desensitization of cyclic AMP signaling not only
      fails to hamper, but actually amplifies PACAP-stimulated CREB-regulated
      transcription.

PMID- 9523560
TI  - Down-regulation of the noradrenaline transporter by interferon-alpha in cultured
      bovine adrenal medullary cells.
AB  - The aim of this study was to investigate the effect of long-term treatment with
      interferon (IFN)-alpha on the noradrenaline transporter of bovine adrenal
      medullary cells. Treatment of cultured adrenal medullary cells with IFN-alpha
      caused a decrease in uptake of [3H]noradrenaline by the cells in time (4-48 h)-
      and concentration (300-1,000 U/ml)-dependent manners. IFN-beta also inhibited
      [3H]noradrenaline uptake to a lesser extent than did IFN-alpha, whereas IFN-gamma
      had little effect. An anti-IFN-alpha antibody reduced the effect of IFN-alpha on
      [3H]noradrenaline uptake. Saturation analysis of [3H]noradrenaline uptake showed
      that the inhibitory effect of IFN-alpha was due to a reduction in the maximal
      uptake velocity (Vmax) values without altering apparent Michaelis constant (Km)
      values. Incubation of cells with IFN-alpha caused a translocation of protein
      kinase C from the soluble to the particulate fraction in the cells. The effect of
      IFN-alpha on [3H]noradrenaline uptake was diminished in protein kinase C-down
      regulated cells. Incubation of cells with IFN-alpha for 48 h significantly
      reduced the specific binding of [3H]desipramine to crude plasma membranes
      isolated from cells. Scatchard analysis of [3H]desipramine binding revealed that
      IFN-alpha decreased the maximal binding (Bmax) values without any change in the
      dissociation constant (K(D)) values. These findings suggest that IFN-alpha
      suppresses the function of noradrenaline transporter by reducing the density of
      the transporter in cell membranes through, at least in part, a protein kinase C
      pathway.

PMID- 9523562
TI  - Beta-amyloid peptides increase the binding and internalization of apolipoprotein
      E to hippocampal neurons.
AB  - The frequency of the epsilon4 allele of apolipoprotein E (apoE) is increased in
      late-onset and sporadic forms of Alzheimer's disease (AD). ApoE also binds to
      beta-amyloid (A beta) and both proteins are found in AD plaques. To further
      investigate the potential interaction of apoE and A beta in the pathogenesis of
      AD, we have determined the binding, internalization, and degradation of human
      apoE isoforms in the presence and absence of A beta peptides to rat primary
      hippocampal neurons. We demonstrate that the lipophilic A beta peptides, in
      particular A beta(1-42), A beta(1-40), and A beta(25-35), increase significantly
      apoE-liposome binding to hippocampal neurons. For each A beta peptide, the
      increase was significantly greater for the apoE4 isoform than for the apoE3
      isoform. The most effective of the A beta peptides to increase apoE binding, A
      beta(25-35), was further shown to increase significantly the internalization of
      both apoE3- and apoE4-liposomes, without affecting apoE degradation. Conversely,
      A beta(1-40) uptake by hippocampal neurons was shown to be increased in the
      presence of apoE-liposomes, more so in the presence of the apoE4 than the apoE3
      isoform. These results provide evidence that A beta peptides interact directly
      with apoE lipoproteins, which may then be transported together into neuronal
      cells through apoE receptors.

PMID- 9523561
TI  - Veratridine-induced depolarization reduces the palmitoylation of brain and myelin
      glycerolipids.
AB  - In this study, we have investigated the effect of neuronal depolarization on the
      palmitoylation of myelin lipids. For this purpose, brain slices from 60-day-old
      rats were incubated with [3H]palmitate for 1 h in the presence or absence of
      various drugs. Veratridine (100 microM) reduced the incorporation of
      [3H]palmitate into all brain glycerolipids by 40-50%, whereas the labeling of
      sphingolipids was unaffected. Similar results were obtained by using [3H]glycerol
      as a precursor, demonstrating that veratridine also causes a reduction in the de
      novo synthesis of glycerolipids. Both tetrodotoxin (1 microM) and ouabain (1 mM)
      prevented the effect of veratridine, indicating that it is mediated through the
      opening of voltage-gated sodium channels and involves the stimulation of the Na+/
      K+ pump. Decreased levels of both ATP, due to activation of the Na+,K+-ATPase,
      and the precursor palmitoyl-CoA were found in the veratridine-treated slices,
      thus explaining the reduction in lipid synthesis. Neuronal depolarization also
      decreased the synthesis of lipids present in the myelin fraction. The relatively
      high specific radioactivity of myelin lipids and the results from both repeated
      purification experiments and mixing experiments ruled out the possibility that
      the radioactive lipids present in myelin could derive from contamination with
      other subcellular fraction(s). Because neither mature oligodendrocytes nor myelin
      is known to express voltage-dependent Na+ channels, it is conceivable that the
      effect of veratridine on myelin glycerolipid metabolism occurs by an indirect
      mechanism such as an increase in the extracellular [K+]. However, the presence of
      60 mM KCl in the medium did not affect the acylation of either brain or myelin
      lipids. These results raise questions as to the absence of sodium channels in
      myelinating oligodendrocytes and/or myelin.

PMID- 9523563
TI  - Ethanol and regulation of the NMDA receptor subunits in fetal cortical neurons.
AB  - Previous studies have shown that chronic ethanol treatment up-regulates the
      expression of the N-methyl-D-aspartate (NMDA) receptor number and function both
      in vitro and in vivo. In vitro chronic ethanol treatment specifically augments
      mRNA levels of the R2B subunit without altering R1 subunit mRNA levels, although
      similar treatment results in increased levels of both R1 and R2B polypeptides. To
      further delineate the molecular mechanisms involved in differential regulation of
      NMDA receptor subunits by chronic ethanol treatment (50 mM, 5 days), we have
      determined the mRNA stability of the NMDA R1 and R2B subunits and the
      transcription rate of the respective genes using mouse fetal cortical neurons.
      Our observations demonstrated that ethanol stabilized the NMDA R1 mRNA over the
      time period examined (24 h) without altering the stability of the R2B mRNA.
      Chronic exposure of fetal cortical neurons to ethanol enhanced the rate of R2B
      gene transcription approximately twofold. Taken together, these results suggest
      that up-regulation of the NMDA receptor number seen in cultured cortical neurons
      after chronic ethanol treatment is due to the regulation of the NMDA R2B receptor
      subunit at the transcriptional level and that of the NMDA R1 subunit mainly at
      the posttranscriptional level.

PMID- 9523564
TI  - Extracellular calcium deprivation in astrocytes: regulation of mRNA expression
      and apoptosis.
AB  - Cell viability and gene expression were studied in primary astroglial cells
      cultured in a nominally calcium-free medium. Ca2+ deprivation reduced
      progressively the astrocytes' viability, starting from 12 h; the restoration of a
      normal Ca2+ concentration (1.8 mM) in the medium after 12-h deprivation reversed
      the degenerative effect within 24 h. Biochemical and morphological examinations
      indicated that cell death induced by Ca2+ deprivation was mediated by apoptosis.
      This was associated with the expression of c-fos, c-jun, and c-myc, which, with
      different time courses, were induced in astrocytes after Ca2+ deprivation.
      Furthermore, shifting to a Ca2+-free medium modified the expression of Ich-1S
      transcript and rapidly increased intracellular cyclic AMP, which has been
      implicated in the transcriptional activation of immediate-early genes. The
      absence of Ca2+ in the medium reduced the expression of constitutive proteins
      such as alpha-actin, clusterin, glial fibrillary acidic protein, amyloid
      precursor protein, and glucose-6-phosphate dehydrogenase. The expression of these
      mRNAs was reduced >50% after 8 h of Ca2+ deprivation, when the effect on cell
      viability was negligible. When Ca2+ deprivation was prolonged for 24 h the
      expression of mRNA dropped completely, and restoration of the Ca2+ ions in the
      medium for 48 h did not reverse this effect. In contrast with general assumption,
      the apoptotic machinery in astrocytes is activated similarly not only by
      increased Ca2+ influx but also with the extracellular Ca2+ deprivation.

PMID- 9523565
TI  - Suppression of astroglial nitric oxide synthase expression by norepinephrine
      results from decreased NOS-2 promoter activity.
AB  - We previously demonstrated that norepinephrine (NE) inhibits induction of the
      calcium-independent isoform of nitric oxide synthase (NOS-2) in primary rat
      astrocyte cultures. However, the molecular mechanisms underlying this effect are
      unknown. In C6 cells and astrocytes, NE suppressed both cytokine- and
      lipopolysaccharide (LPS)-dependent nitrite accumulation, an index of NOS-2
      activity. NE reduced the steady-state levels of NOS-2 mRNA induced by LPS plus
      cytokines but did not decrease NOS-2 mRNA stability or inhibit activation or
      subunit composition of transcription factor nuclear factor kappaB, which is
      necessary for NOS-2 induction. In C6 cells stably transfected with a 1,588-bp
      mouse NOS-2 promoter, NE reduced LPS plus cytokine-induced reporter gene
      expression, suggesting inhibition of NOS-2 promoter activity. In contrast,
      suppression was lost when a truncated 85-bp NOS-2 promoter was used, and in these
      cells NE potentiated reporter gene expression, alone or in the presence of LPS
      and cytokines. These results suggest that the suppressive effects of NE are due
      to modification of transcription factor activity in a region located between 
      1,588 and -85 of the NOS-2 promoter and may help explain observations that in
      some cells cyclic AMP can potentiate, rather than suppress, NOS-2 expression.

PMID- 9523567
TI  - Increase of extracellular glutamate and expression of Fos-like immunoreactivity
      in the ventral tegmental area in response to electrical stimulation of the
      prefrontal cortex.
AB  - Electrical stimulation of the medial prefrontal cortex caused glutamate release
      in the ventral tegmental area (VTA) of freely moving animals. Cathodal
      stimulation was given through monopolar electrodes in 0.1-ms pulses at an
      intensity of 300 microA and frequencies of 4-120 Hz. Glutamate was measured in 10
      min perfusate samples by HPLC coupled with fluorescence detection following
      precolumn derivatization with o-phthaldialdehyde/beta-mercaptoethanol. The
      stimulation-induced glutamate release was frequency dependent and was blocked by
      the infusion of the sodium channel blocker tetrodotoxin (10 microM) through the
      dialysis probe. The stimulation also induced bilateral Fos-like immunoreactivity
      in ventral tegmental neurons, with a significantly greater number of Fos-positive
      cells on the stimulated side. These findings add to a growing body of evidence
      suggesting that the medial prefrontal cortex regulates dopamine release in the
      nucleus accumbens via its projection to dopamine cell bodies in the VTA.

PMID- 9523566
TI  - Repeated cocaine administration alters extracellular glutamate in the ventral
      tegmental area.
AB  - The present study determined if repeated cocaine injections alter the effect of
      cocaine on extracellular glutamate in the ventral tegmental area (VTA). All rats
      were treated with daily cocaine (15 mg/kg i.p. x 2 days, 30 mg/kg i.p. x 5 days)
      or saline for 7 days. At 21 days after discontinuing the daily injections, a
      dialysis probe was placed into the VTA and the extracellular levels of glutamate
      were estimated. A systemic injection of cocaine (15 mg/kg i.p.) elevated
      extracellular glutamate in the VTA of rats pretreated with daily cocaine but not
      in the daily saline-pretreated subjects. No significant change in glutamate was
      produced by a saline injection in either pretreatment group. In a group of rats
      pretreated with daily cocaine, the D1 antagonist SCH-23390 (30 microM) was
      infused through the dialysis probe prior to the acute injections of saline and
      cocaine. SCH-23390 prevented the increase in extracellular glutamate associated
      with the acute administration of cocaine. Behavioral data were collected
      simultaneously with the measures of extracellular glutamate. The behavioral
      stimulant effect of cocaine was greater in cocaine-pretreated than saline
      pretreated subjects, and the behavioral augmentation in cocaine-pretreated rats
      was partly blocked by SCH-23390. These data support the hypotheses that repeated
      cocaine administration produces an increase in the capacity of D1 receptor
      stimulation to release glutamate in the VTA and that this mechanism partly
      mediates behavioral sensitization produced in rats treated with daily cocaine
      injections.

PMID- 9523568
TI  - Presynaptic GABA(B) receptor modulation of glutamate exocytosis from rat
      cerebrocortical nerve terminals: receptor decoupling by protein kinase C.
AB  - GABA and the GABA(B) receptor agonist (-)-baclofen inhibited 4-aminopyridine
      (4AP)- and KCl-evoked, Ca2+-dependent glutamate release from rat cerebrocortical
      synaptosomes. The GABA(B) receptor antagonist CGP 35348, prevented this
      inhibition of glutamate release, but phaclofen had no effect. (-)-Baclofen
      mediated inhibition of glutamate release was insensitive to 2 microg/ml pertussis
      toxin. As determined by examining the mechanism of GABA(B) receptor modulation of
      glutamate release, (-)-baclofen caused a significant reduction in 4AP-evoked Ca2+
      influx into synaptosomes. The agonist did not alter the resting synaptosomal
      membrane potential or 4AP-mediated depolarization; thus, the inhibition of Ca2+
      influx could not be attributed to GABA(B) receptor activation causing a decrease
      in synaptosomal excitability. Ionomycin-mediated glutamate release was not
      affected by (-)-baclofen, indicating that GABA(B) receptors in this preparation
      are not coupled directly to the exocytotic machinery. Instead, the data invoke a
      direct coupling of GABA(B) receptors to voltage-dependent Ca2+ channels linked to
      glutamate release. This coupling was subject to regulation by protein kinase C
      (PKC), because (-)-baclofen-mediated inhibition of 4AP-evoked glutamate release
      was reversed when PKC was stimulated with phorbol ester. This may therefore
      represent a mechanism by which inhibitory and facilitatory presynaptic receptor
      inputs interplay to fine-tune transmitter release.

PMID- 9523569
TI  - Cyclic AMP resets the circadian clock in cultured Xenopus retinal photoreceptor
      layers.
AB  - The Xenopus retinal photoreceptor layer contains a circadian oscillator that
      regulates melatonin synthesis in vitro. The phase of this oscillator can be reset
      by light or dopamine. The phase-response curves for light and dopamine are
      similar, with transitions from phase delays to phase advances in the mid
      subjective night. Light and dopamine each can inhibit adenylate cyclase in
      retinal photoreceptors, suggesting cyclic AMP as a candidate second messenger for
      entrainment of the circadian oscillator. We report here that treatments that
      increase intracellular cyclic AMP reset the phase of the photoreceptor circadian
      oscillator, and that the phase-response curves for these treatments are 180
      degrees out of phase with the phase-response curves for light and dopamine.
      Activation of adenylate cyclase by forskolin during the late subjective day or
      early subjective night caused phase advances. The same treatment during the late
      subjective night or early subjective day caused phase delays. Similar phase
      shifts were induced by 3-isobutyl-1-methylxanthine (a phosphodiesterase
      inhibitor) or 8-(4-chlorophenylthio)cyclic AMP. All of these treatments also
      acutely increased melatonin release. Forskolin and 3-isobutyl-1-methylxanthine
      increased the accumulation of intracellular cyclic AMP, but not cyclic GMP, in
      photoreceptor layers. The results indicate that cyclic AMP-dependent pathways
      regulate the photoreceptor circadian oscillator and suggest that a decrease in
      cyclic AMP may be involved in circadian entrainment by light and/or dopamine.

PMID- 9523570
TI  - Effects of local administration of L-, N-, and P/Q-type calcium channel blockers
      on spontaneous dopamine release in the striatum and the substantia nigra: a
      microdialysis study in rat.
AB  - The pivotal role for voltage-sensitive calcium channels in initiating synaptic
      transmitter release is undisputed, but it is only partly known to what extent the
      different subtypes contribute in vivo. Their importance for the dendritic release
      of dopamine has not been investigated in vivo previously. To evaluate
      comprehensively the relative importance of different voltage-sensitive calcium
      channel subtypes for striatal dopamine release, and to further investigate the
      mechanism of dendritic dopamine release in the reticulate part of substantia
      nigra, dopamine was measured by in vivo microdialysis in the striatum or
      substantia nigra of awake rats. The calcium channel blockers nimodipine, omega
      conotoxin-GVIA, omega-agatoxin-IVA, and neomycin were administered locally
      through the dialysis probes and compared with calcium-free perfusion. Results
      indicate that dopamine release in the striatum is mainly dependent on N- and P/Q
      type channels, but the dendritic dopamine release in the substantia nigra is
      mediated mainly by some other calcium-dependent mechanism, for example, calcium
      mobilization through T-, O-, or R-type calcium channels. A portion of the
      dendritic release is calcium independent but can be inhibited partially by
      neomycin, which might suggest a role for inositol 4,5-bisphosphate breakdown
      products.

PMID- 9523571
TI  - Nitric oxide causes glutamate release from brain synaptosomes.
AB  - We determined the ability of pathological levels of nitric oxide (NO) to cause
      glutamate release from isolated rat brain nerve terminals using a fluorometric
      assay. It was found that NO (0.7 and 2 microM) produced (4 and 10 nmol/mg of
      synaptosomal protein) Ca2+-independent glutamate release from synaptosomes (after
      1 min of exposure). Spermine/NO complex (spermine NONOate; a slow NO donor) and
      potassium cyanide (an inhibitor of cytochrome oxidase) also caused Ca2+
      independent glutamate release. Preincubation of synaptosomes with 5 microM 1H
      [1,2,4]oxadiazole[4,3-a]quinoxalin-1-one (an inhibitor of soluble guanylyl
      cyclase) had no effect on NO-induced Ca2+-independent glutamate release. Ca2+
      independent glutamate release produced by NO was greater in a low-oxygen medium.
      NO, spermine NONOate, and potassium cyanide inhibited synaptosomal respiration
      with a similar order of potency with respect to their ability to cause glutamate
      release. Because NO has been shown previously to inhibit reversibly cytochrome
      oxidase in competition with oxygen, our findings in this study suggest that NO
      (and cyanide) causes glutamate release following inhibition of mitochondrial
      respiration at the level of cytochrome oxidase. Thus, elevated NO production
      leading to mitochondrial dysfunction, glutamate release, and excitotoxicty may
      contribute to neuronal death in neurological diseases.

PMID- 9523572
TI  - Down-regulation of the human norepinephrine transporter in intact 293-hNET cells
      exposed to desipramine.
AB  - The effects of continuous exposure of cultured cells expressing the human
      norepinephrine transporter (hNET) to the hNET inhibitor desipramine on hNET
      expression and function were studied. Exposure of HEK-293 cells transfected
      stably with the hNET cDNA (293-hNET cells) to desipramine for 3 days reduced the
      specific binding of [3H]nisoxetine in membrane homogenates in a concentration
      dependent manner. The magnitude of the reductions in [3H]nisoxetine binding to
      hNET was dependent on the length of time of the exposure to desipramine, reaching
      77% after a 21-day exposure. The reduction of [3H]nisoxetine binding returned to
      control levels within 72 h after a 3-day exposure to desipramine. Reductions in
      [3H]nisoxetine binding to hNET were accompanied by time-dependent and exposure
      concentration-dependent reductions in hNET protein levels as determined by
      western blotting. Similar to binding, hNET protein levels returned to control
      levels 72 h after cessation of desipramine exposure. Northern blotting indicated
      that exposure of 293-hNET cells to desipramine did not significantly alter hNET
      mRNA levels. Uptake of [3H]norepinephrine by 293-hNET cells was markedly reduced
      after a 3-day exposure to desipramine. However, desipramine exposure had no
      effect on uptake of [3H]glutamate or [3H]alanine. The present findings imply that
      down-regulation of the hNET in 293-hNET cells induced by desipramine results from
      a selective reduction in hNET protein levels, presumably a consequence of either
      a reduction in the translation of hNET mRNA or from an enhanced degradation of
      hNET protein.

PMID- 9523573
TI  - Effect of immobilization stress on transcriptional activity of inducible
      immediate-early genes, corticotropin-releasing factor, its type 1 receptor, and
      enkephalin in the hypothalamus of borderline hypertensive rats.
AB  - The effects of immobilization on the expression of immediate-early gene c-fos and
      nerve growth factor-inducible (NGFI)-B mRNAs, corticotropin-releasing factor
      (CRF) mRNA, CRF heteronuclear RNA (hnRNA), CRF receptor types 1 and 2alpha mRNA,
      and enkephalin hn/mRNA were investigated in the hypothalamic paraventricular
      nucleus of Wistar-Kyoto (WKY) rats and borderline hypertensive rats (BHRs). Rats
      were deeply anesthetized 0, 30, 60, and 180 min after the beginning of the
      immobilization session (60 min maximum). BHR paraventricular nuclei displayed
      slight differences in their resting levels of NGFI-B mRNA and CRF hnRNA, both
      being significantly elevated compared with those of WKY rats. Conversely, basal
      levels of enkephalin primary transcript were significantly lower in BHRs.
      Immobilization, however, induced transient variations in the hybridization
      signals for all evaluated genes within the paraventricular nucleus (except for
      CRF 2alpha receptor). Immediate-early gene mRNA levels were higher and more
      prolonged in BHRs than in WKY rats. This heightened neuronal activation in the
      BHRs was associated with a more rapid increase in CRF mRNA expression (30 min)
      compared with that in WKY rats (60 min). It is interesting that a transient rise
      in CRF hnRNA levels was detected in stressed WKY rats, whereas the BHR group
      displayed a progressive decline in this transcript, being significantly below
      resting levels 180 min after the immobilization session. The stress-induced
      expression of CRF type 1 receptor mRNA was similar in both strains. Moreover, no
      significant differences were observed for enkephalin hn/mRNA in either strain
      during the immobilization session. Therefore, the hypothalamic paraventricular
      nucleus appears to be involved in the functional hyperreactivity of the
      hypothalamic-pituitary-adrenal and autonomic axes to stress observed in BHRs,
      which may lead ultimately to a stress-induced hypertensive state.

PMID- 9523575
TI  - Substance P and histamine induce interleukin-6 expression in human astrocytoma
      cells by a mechanism involving protein kinase C and nuclear factor-IL-6.
AB  - Interleukin-6 (IL-6) is a proinflammatory cytokine whose synthesis is induced by
      a variety of stimuli including interleukin-1 (IL-1), substance P (SP), and
      histamine. Because IL-6 has been implicated in the etiopathology of different
      human diseases including multiple myeloma, rheumatoid arthritis, multiple
      sclerosis, acquired immunodeficiency syndrome dementia complex, and Alzheimer's
      disease, its inhibition may be of therapeutic interest. A main demand on an
      effective inhibitor of IL-6 expression is that it inhibits IL-6 synthesis
      independently of the inducing stimulus. We therefore used human astrocytoma cells
      to search for signal transduction cascades and transcription factors whose
      inhibition suppresses IL-6 synthesis after stimulation with three different
      inductors, IL-1beta, SP, and histamine. Whereas the antioxidant
      pyrrolidinedithiocarbamate was only able to inhibit IL-1beta-induced IL-6
      expression, inhibition of protein kinase C prevented IL-6 expression induced by
      all three substances. Promoter deletion analysis revealed that IL-1beta-induced
      IL-6 expression required the transcription factor nuclear factor-kappaB (NF
      kappaB), whereas SP- and histamine-induced IL-6 synthesis was essentially
      controlled by NF-IL-6. These findings suggest that inhibition of protein kinase C
      or a combinatory inhibition of NF-IL-6 and NF-kappaB binding are strategies to
      effectively suppress IL-6 synthesis. They therefore provide the basis for the
      development of antiinflammatory drugs used to treat disorders in which IL-6 is
      pathogenically involved.

PMID- 9523574
TI  - Endomorphin-stimulated [35S]GTPgammaS binding in rat brain: evidence for partial
      agonist activity at mu-opioid receptors.
AB  - Endomorphin-1 is a peptide whose binding selectivity suggests a role as an
      endogenous ligand at mu-opioid receptors. In the present study, the effect of
      endomorphin-1 on mu receptor-coupled G proteins was compared with that of the mu
      agonist DAMGO by using agonist-stimulated [35S]GTPgammaS binding in rat brain.
      [35S]GTPgammaS autoradiography revealed a similar localization of endomorphin-1-
      and DAMGO-stimulated [35S]GTPgammaS binding in areas including thalamus, caudate
      putamen, amygdala, periaqueductal gray, parabrachial nucleus, and nucleus tractus
      solitarius. Naloxone blocked endomorphin-1-stimulated labeling in all regions
      examined. Although the distribution of endomorphin-1-stimulated [35S]GTPgammaS
      binding resembled that of DAMGO, the magnitude of endomorphin-1-stimulated
      binding was significantly lower than that produced by DAMGO. Concentration-effect
      curves of endomorphin-1 and DAMGO in thalamic membranes confirmed that
      endomorphin-1 produced only 70% of DAMGO-stimulated [35S]GTPgammaS binding.
      Differences in maximal stimulation of [35S]GTPgammaS binding between DAMGO and
      endomorphin-1 were magnified by increasing GDP concentrations, and saturation
      analysis of net endomorphin-1-stimulated [35S]GTPgammaS binding revealed a lower
      apparent Bmax value than that obtained with DAMGO. Endomorphin-1 also partially
      antagonized DAMGO stimulation of [35S]GTPgammaS binding. These results
      demonstrate that endomorphin-1 is a partial agonist for G protein activation at
      the mu-opioid receptor in brain.

PMID- 9523576
TI  - Expression, purification, and encephalitogenicity of recombinant human myelin
      oligodendrocyte glycoprotein.
AB  - Myelin oligodendrocyte glycoprotein (MOG), a putative autoantigen in multiple
      sclerosis (MS), is a quantitatively minor component of the CNS. In view of the
      difficulties associated with the purification of MOG from brain tissues, the
      extracellular domain of human MOG corresponding to the N-terminal 121 amino acids
      was expressed in Escherichia coli as a glutathione sulfotransferase fusion
      protein. The expressed protein was localized to inclusion bodies, and varying the
      growth parameters resulted in the solubilization of small amounts of GST-MOG that
      could be affinity purified on glutathione agarose columns. The fusion protein
      found in the inclusion bodies could be solubilized with urea. The solubilized
      fusion protein was cleaved with thrombin, and the extracellular domain was
      purified by CM Sephadex 50 chromatography to homogeneity. Injection of
      recombinant human MOG into different strains of mice resulted in the induction of
      an MS-like disease, characterized by severe neurological impairment and extensive
      CNS demyelinated lesions. Recombinant MOG produced in E. coli should prove to be
      useful as a highly purified biological reagent for immunological, pathological,
      functional, and structural studies.

PMID- 9523577
TI  - Decreased expression of calmodulin kinase II and calcineurin messenger RNAs in
      the mouse hippocampus after kainic acid-induced seizures.
AB  - The Ca2+/calmodulin-dependent protein kinase II (CaMKII) and the phosphatase
      calcineurin (CaN) are especially abundant in the mammalian CNS, where they have
      been implicated repeatedly in different neuronal functions. CaMKII is a
      holoenzyme that is likely to be constituted of both homomultimers and
      heteromultimers, CaMKIIalpha and CaMKIIbeta being the most abundant subunits in
      the brain. CaN is a heterodimer constituted of a catalytic subunit (CaN A) and a
      regulatory subunit (CaN B), and CaN Aalpha is the predominant form in the brain.
      We studied the expression of CaMKIIalpha, CaMKIIbeta, and CaN Aalpha subunit
      messenger RNAs in the mouse hippocampus at different times after the
      administration of a convulsant dose of kainic acid. CaMKIIalpha and CaN A
      immunohistochemistry was also performed. We observed a transient decrease in the
      three messenger RNAs in the kainic acid-treated mice, peaking at 5 or 24 h of
      treatment. The effect had disappeared completely 8 days after treatment. No
      significant alterations in CaMKII or CaN immunolabelling were observed in the
      hippocampus of kainic acid-treated mice. The observed modifications could be due
      to the neuronal hyperexcitability induced by kainic acid rather than neuronal
      degeneration, because no areas of neuronal loss were detected. Our results
      suggest that the expression of CaMKII and CaN mRNAs is down-regulated in neuronal
      cells in response to the hyperexcitability induced by kainic acid. The transient
      nature of the effect and the apparent absence of significant modifications in the
      amount of their corresponding proteins may be related to the absence of neuronal
      damage.

PMID- 9523578
TI  - Distinct changes in peptide YY binding to, and mRNA levels of, Y1 and Y2
      receptors in the rat hippocampus associated with kindling epileptogenesis.
AB  - Electrical kindling of the rat dorsal hippocampus induced significant changes in
      the binding of 125I-peptide YY to Y1 and Y2 subtypes of neuropeptide Y receptors
      and in their mRNA levels in the area dentata as assessed by quantitative receptor
      autoradiography and in situ hybridization histochemistry. Binding to Y1 receptor
      sites decreased by 50% (p < 0.05) in the molecular layer of the stimulated
      dentate gyrus, 2 days after preconvulsive stage 2 and 1 week or 1 month after
      generalized stage 5 seizures compared with sham-stimulated rats. Binding to Y2
      receptor sites increased bilaterally by 36-87% (p < 0.05) in the hilus at stage 2
      and 1 week or 1 month after stage 5. No significant changes were observed after
      one afterdischarge or in the other hippocampal subfields or in the cortex. Y1
      receptor mRNA signal decreased bilaterally by 50-64% (p < 0.01) in the granule
      cell layer, 6 h but not 24 h after stages 2 and 5. The Y2 receptor mRNA signal
      was enhanced by 283% (p < 0.01) in the stimulated granule cell layer 24 h after
      stage 2. At 6 and 24 h after stage 5, mRNA levels were increased both
      ipsilaterally (283 and 360%, respectively; p < 0.01) and contralaterally (190 and
      260%, respectively; p < 0.05). No significant changes in level of either mRNA was
      found following one afterdischarge. These modifications, and the enhanced
      neuropeptide Y release previously shown in the hippocampus, suggest that kindling
      is associated with lasting changes in neuropeptide Y-mediated neurotransmission.

PMID- 9523579
TI  - Protection against beta-amyloid toxicity in primary neurons by paclitaxel
      (Taxol).
AB  - Neurofibrillary tangles in Alzheimer's disease contain aggregates of abnormally
      phosphorylated microtubule-associated protein tau, indicating that microtubule
      breakdown is a primary event in the neurodegenerative cascade. Recent studies
      have shown that addition to neuronal cultures of amyloid peptides found in
      Alzheimer's leads to abnormal phosphorylation of tau and neurofibrillary
      pathology. We tested the possibility that the microtubule-stabilizing drug
      paclitaxel (Taxol) might protect primary neurons against amyloid-induced
      toxicity. Neurons exposed to aggregated amyloid peptides 25-35 and 1-42 became
      pyknotic with degenerating neurites within 24 h. Treatment of cultures with
      paclitaxel either 2 h before or 2 h after addition of the peptide prevented these
      morphological alterations. When numbers of viable cells were determined in
      cultures exposed to amyloid peptide with or without paclitaxel for 24 or 96 h,
      the percentage of surviving cells was significantly higher in paclitaxel-treated
      cultures, and activation of the apoptosis-associated protease CPP32 was
      significantly reduced. These observations indicate that microtubule-stabilizing
      drugs may help slow development of the neurofibrillary pathology that leads to
      the loss of neuronal integrity in Alzheimer's disease.

PMID- 9523580
TI  - Analysis of local structure in the D2/S1-S2 region of the rat skeletal muscle
      type 1 sodium channel using insertional mutagenesis.
AB  - A reporter epitope was inserted at 11 positions in a region encompassing proposed
      transmembrane segments S1 and S2 in the second repeat domain (D2) of the rat
      skeletal muscle type 1 sodium channel. All mutations produced full-length
      membrane-associated protein following transfection into cultured cells, although
      the level of expression varied with insertion position. Characterization of
      cognate cRNAs for each mutation in Xenopus oocytes by two-electrode voltage clamp
      defined a permissive region between the proposed transmembrane regions in which
      these large insertions did not interfere with channel function. Two of the
      mutations, in which the point of insertion was within the proposed S1-S2 loop,
      demonstrated extracellular membrane labeling when studied either by antibody
      binding in oocytes or by confocal analysis following transfection into primary
      muscle cells. Our results define the likely boundaries of an extramembrane region
      linking the S1 and S2 transmembrane segments in D2 and confirm the extracellular
      location of this S1-S2 loop predicted by current models of channel tertiary
      structure.

PMID- 9523581
TI  - Tetanus toxin enhances protein kinase C activity translocation and increases
      polyphosphoinositide hydrolysis in rat cerebral cortex preparations.
AB  - Tetanus toxin (TeTx) has been recently demonstrated to be a Zn2+-dependent
      endopeptidase that cleaves synaptobrevin, a protein in part responsible for
      neurotransmitter release. Nevertheless, certain aspects of TeTx action, for
      example, the causal relationship between TeTx and protein kinase C (PKC; EC
      2.7.1.37) activity cannot be explained by this cleavage alone. In the present
      study, primary neurons from fetal rat brain, synaptosomes, and whole slices have
      been used to examine this issue. Low doses of TeTx (< or = 10(-8) M) caused PKC
      activity translocation in a manner similar to that produced by 12-O
      tetradecanoylphorbol 13-acetate (TPA). TPA (< or = 10(-7) M) caused sustained PKC
      activity translocation, whereas TeTx produced translocation followed by
      relocation, depending on the dose and time of exposure. Immunoidentification with
      a monoclonal antibody recognizing both alpha and beta isoforms revealed that TeTx
      induced moderate losses of PKC in the cytosolic fraction, without a comparable
      increase in the particulate fraction. Although moderate losses of activity were
      also noticed in the cytosolic fraction, the inconsistency with respect to
      activity translocation may be explained by translocation of additional PKC
      isoforms that are not identified by the antibody. Comparable levels of water
      soluble inositol phosphate-labeled intermediates were obtained after treatment of
      cerebral cells and/or cortical brain slices with TeTx. Significant increases of
      19 and 114% in the water-soluble myo-[2-(3)H]inositol-labeled inositol phosphate
      metabolites were found in cerebral cell culture and brain slices, respectively,
      after treatment with 10(-8) M TeTx. TeTx (10(-8) M) increased to the same degree
      the water-soluble inositol phosphate levels as did serotonin (10(-5) M) or
      carbachol (10(-6) M). It is suggested that part of the signaling cascade of TeTx
      consists of a component involving inositol phospholipid hydrolysis, which is
      associated with PKC activity translocation.

PMID- 9523582
TI  - Identification, characterization, immunocytochemical localization, and
      developmental changes in the activity of calcium/calmodulin-dependent protein
      kinase II in the CNS of Bombyx mori during postembryonic development.
AB  - In the present investigation, in vitro phosphorylation of CNS proteins of the
      silkworm Bombyx mori during the postembryonic development have been studied.
      Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography of
      phosphorylated proteins revealed the presence of major phosphoproteins of 59/60
      kDa. Based on molecular mass, calcium/calmodulin-dependent autophosphorylation,
      substrate specificity, KN-62 inhibition, apparent Km for ATP and syntide-2, these
      proteins were identified as calcium/calmodulin-dependent protein kinase II (CaM
      kinase II). Anti-rat CaM kinase II monoclonal antibody showed immunoreactivity
      with Bombyx CaM kinase II isoforms. This kinase showed a high degree of
      autophosphorylation in neural tissue. During postembryonic development of Bombyx,
      two distinct peaks of enzyme activity could be noticed, one at the late-larval
      and another at the late-pupal stage, which were associated with an increase in
      amount of the enzyme. These results suggested that the expression of CaM kinase
      II in the CNS of Bombyx was developmentally regulated.

PMID- 9523583
TI  - Pituitary adenylate cyclase-activating polypeptide causes Ca2+ release from
      ryanodine/caffeine stores through a novel pathway independent of both inositol
      trisphosphates and cyclic AMP in bovine adrenal medullary cells.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) causes both Ca2+
      release and Ca2+ influx in bovine adrenal chromaffin cells. To elucidate the
      mechanisms of PACAP-induced Ca2+ release, we investigated expression of PACAP
      receptors and measured inositol trisphosphates (IP3), cyclic AMP, and the
      intracellular Ca2+ concentration in bovine adrenal medullary cells maintained in
      primary culture. RT-PCR analysis revealed that bovine adrenal medullary cells
      express the PACAP receptor hop, which is known to couple with both IP3 and cyclic
      AMP pathways. The two naturally occurring forms of PACAP, PACAP38 and PACAP27,
      both increased cyclic AMP and IP3, and PACAP38 was more potent than PACAP27 in
      both effects. Despite the effects of PACAP on IP3 production, the Ca2+ release
      induced by PA-CAP38 or by PACAP27 was unaffected by cinnarizine, a blocker of IP3
      channels. The potencies of the peptides to cause Ca2+ release in the presence of
      cinnarizine were similar. The Ca2+ release induced by PACAP38 or by PACAP27 was
      strongly inhibited by ryanodine and caffeine. In the presence of ryanodine and
      caffeine, PACAP38 was more potent than PACAP27. PACAP-induced Ca2+ release was
      unaffected by Rp-adenosine 3',5'-cyclic monophosphothioate, an inhibitor of
      protein kinase A. Ca2+ release induced by bradykinin and angiotensin II was also
      inhibited by ryanodine and caffeine, but unaffected by cinnarizine. Although IP3
      production stimulated by PACAP38 or bradykinin was abolished by the phospholipase
      C inhibitor, U-73122, Ca2+ release in response to the peptides was unaffected by
      U-73122. These results suggest that PACAP induces Ca2+ release from
      ryanodine/caffeine stores through a novel intracellular mechanism independent of
      both IP3 and cyclic AMP and that the mechanism may be the common pathway through
      which peptides release Ca2+ in adrenal chromaffin cells.

PMID- 9523584
TI  - Disruption by lithium of phosphoinositide signalling in cerebellar granule cells
      in primary culture.
AB  - Mild depolarisation (20 mM KCl) synergistically enhances the ability of a
      muscarinic agonist to activate phosphoinositide turnover and to elevate inositol
      1,4,5-trisphosphate [Ins(1,4,5)P3] in cerebellar granule cells in primary
      culture. The effects of lithium on this intense stimulation of phosphoinositide
      turnover was studied. Lithium causes depletion of cytoplasmic inositol and
      phosphoinositides, which results in the inhibition of phosphoinositide turnover
      within 15 min and the return of Ins(1,4,5)P3 to basal levels at this time. This
      inhibition could not be reversed by culturing and preincubating cerebellar
      granule cells in concentrations of inositol similar to those detected in the CSF.
      Inositol concentrations substantially in excess of those in the CSF not only
      reversed the effects of lithium on stimulated Ins(1,4,5)P3 levels, but
      significantly enhanced this level in comparison with stimulation in the absence
      of lithium. sn-1,2-Diacylglycerol elevation during stimulated phosphoinositide
      turnover was also disrupted by lithium, but in contrast to Ins(1,4,5)3, the
      presence of lithium resulted in a transient enhancement of the elevation evoked
      by carbachol plus mild KCl depolarisation, which was reversed by 500 microM
      inositol, but not by 200 microM inositol. The implications of these phenomena in
      relation to the mechanism of action of lithium in the treatment of manic
      depression are discussed.

PMID- 9523585
TI  - Differential cleavage of provasopressin by the major molecular forms of SPC3.
AB  - We have investigated the roles of full-length and carboxyl-terminus-truncated
      forms of the subtilisin-like prohormone convertase SPC3 in the processing of the
      radiolabeled vasopressin and oxytocin precursors, in vitro. We found SPC3 cleaves
      provasopressin at both the vasopressin-neurophysin and neurophysin-glycopeptide
      processing sites. Prooxytocin is cleaved by SPC3 at the oxytocin-neurophysin
      cleavage site. However, our results reveal differences in processing of
      provasopressin by the different molecular forms of SPC3. In incubations where the
      rate of autocatalytic carboxyl-terminus truncation of SPC3 was dramatically
      reduced, 86-kDa SPC3, which has an unprocessed carboxyl terminus, cleaved
      provasopressin at the neurophysin-glycopeptide junction. Cleavage at the
      vasopressin-neurophysin junction only occurred with the appearance of carboxyl
      terminus-truncated forms of the enzyme. Incubations containing 64-kDa SPC3 or 64
      kDa SPC3-T, a recombinant form of SPC3 truncated 14 amino acids beyond the
      conserved carboxyl-terminal "P-domain," rapidly cleaved provasopressin at both
      the vasopressin-neurophysin and neurophysin-glycopeptide junctions. Our results
      also suggest that prooxytocin is unable to be cleaved by the 86-kDa form of SPC3.
      We propose that SPC3 should be considered as a candidate endoprotease in the
      biosynthesis of vasopressin. Furthermore, we suggest that the carboxyl terminus
      of SPC3 alters the cleavage specificity of SPC3.

PMID- 9523586
TI  - Glutamatergic activation of hippocampal phospholipase D: postnatal fading and
      receptor desensitization.
AB  - Phospholipase D (PLD) activity was determined in rat hippocampal slices between
      postnatal days 3 and 35. After birth, basal PLD activity was low and, within 2
      weeks, increased to reach a plateau that was maintained up to the adult age.
      Likewise the response to glutamate developed postnatally to reach a maximum at
      day 8, but then faded rapidly and was almost absent at day 35. Activation of PLD
      by 4beta-phorbol 12beta,13alpha-dibutyrate (PDB) was independent of age, whereas
      the effect of aluminum fluoride (AlF4-) increased to a plateau within the first
      week. At day 8, PLD stimulation by glutamate via metabotropic receptors involved
      protein kinase C activation, but was independent of Ca2+ influx; the time course
      of PLD activation by PDB or AlF4- was linear throughout the experiment, whereas
      the response to glutamate or 1-aminocyclopentane-1,3-dicarboxylic acid followed a
      biphasic pattern: the rapid "first phase activation" desensitized within a few
      minutes and disclosed a small, but maintained "second phase." Pretreatment
      experiments confirmed desensitization of PLD activation by glutamate, but not by
      AlF4- or PDB. The biphasic pattern of glutamatergic PLD activation changed during
      development, i.e., the first phase activation faded and the second phase
      remained. These results were fully confirmed by the time courses of the PLD
      mediated efflux of choline evoked by glutamate. In conclusion, postnatal
      glutamatergic activation of hippocampal PLD is composed of a pronounced and
      desensitizing first phase activation and a small, but nondesensitizing second
      phase. The first, but not the second, phase activation fades rapidly during
      development. The hypothesis is discussed that the glutamatergic activation of PLD
      occurs along different pathways in neonate and adult tissue.

PMID- 9523587
TI  - Effects of copper on survival of prion protein knockout neurons and glia.
AB  - The N-terminal region of the prion protein (PrP) contains an octameric repeat
      region suggested to bind copper. A 32-amino acid peptide (PrPOcta) based on this
      region in the protein was tested for its effects on cultured cerebellar cells.
      Cerebellar cells from mice deficient in cellular PrP (Prnp0/0 mice) are more
      sensitive to copper toxicity and oxidative stress. PrPOcta selectively promotes
      the survival of Prnp0/0 cerebellar cells. However, PrPOcta also reduces the
      toxicity of CuSO4 on cerebellar cells and abolishes the difference in increased
      sensitivity of Prnp0/0 cells to both copper toxicity and also oxidative stress
      from xanthine oxidase. PrPOcta does not promote the survival or proliferation of
      astrocytes or microglia. The survival-promoting effects of PrPOcta on neurons may
      be due to its ability to effectively chelate copper. The octameric repeat region
      of PrP may represent a functional domain of the native protein.

PMID- 9523588
TI  - Involvement of receptor cycling and receptor reserve in resensitization of
      muscarinic responses in SH-SY5Y human neuroblastoma cells.
AB  - Preexposure of SH-SY5Y cells to the muscarinic agonist carbachol caused a rapid
      desensitization of subsequent carbachol-stimulated intracellular Ca2+ responses
      and a slower decrease in the number of receptors at the plasma membrane.
      Desensitization (to 30% of the control response) was maximal after 1 min of
      exposure to agonist, whereas the number of cell surface receptors reached a
      minimum (33% of control) only after 5 min. Following agonist washout, the
      recovery of response was complete within 12 min, whereas the recovery of surface
      receptor number reached a plateau at 65% of control after 30 min. Treatment with
      inhibitors of endocytosis (concanavalin A) or recycling (nigericin) did not
      affect rapid desensitization but did decrease resensitization, suggesting that
      receptor cycling is involved in resensitization. Experiments with the
      irreversible antagonist propylbenzilylcholine mustard demonstrated that the
      receptor reserve for the Ca2+ response to 1 mM carbachol is approximately 50%.
      Removal of this receptor reserve led to a decrease in the rate of
      resensitization. We propose that the existence of a receptor reserve might
      explain the poor correlation between functional response and surface receptor
      number, and that one of its roles might be to permit rapid resensitization after
      a significant agonist-induced decrease in surface receptor number. The purpose of
      receptor cycling might be to allow dephosphorylation (and reactivation) of
      receptors that have become phosphorylated (and inactivated) in response to
      agonist stimulation, because the protein phosphatase inhibitor calyculin A
      significantly reduced resensitization.

PMID- 9523589
TI  - Expression of the oligodendrocyte-myelin glycoprotein by neurons in the mouse
      central nervous system.
AB  - The oligodendrocyte-myelin glycoprotein (OMgp) is a 110-kDa
      glycosylphosphatidylinositol-linked protein that was initially identified as a
      myelin-specific protein but whose precise function remains unknown. In this
      study, immunohistochemistry, western blots, in situ hybridization, and northern
      blots were used to determine the distribution of OMgp in the mouse brain. OMgp is
      present in a concentration detectable on western blots in the brains of newborn
      mice, and its concentration gradually increases until day 24 of life. OMgp mRNA
      is also present in amounts detectable on northern blots in the brains of newborn
      mice, and its concentration gradually increases until day 21 of life, after which
      the concentration diminishes a little. Most of the OMgp in the mouse brain
      appears to be expressed in diverse groups of neurons, but it is particularly
      prominent in large projection neurons such as the pyramidal cells of the
      hippocampus, the Purkinje cells of the cerebellum, motoneurons in the brainstem,
      and anterior horn cells of the spinal cord. However, OMgp is not confined to
      these cells and is expressed in cells in the white matter as well. The OMgp gene
      is placed within an intron of the neurofibromatosis type I gene and on the
      opposite strand. This organization raises the possibility that there may be a
      relationship between the functions of the products of the two genes. In support
      of this possibility, we show that within the mouse CNS OMgp and neurofibromin are
      expressed in the same cell types.

PMID- 9523590
TI  - Structure-activity relationships of conformationally constrained peptide
      analogues of loop 2 of brain-derived neurotrophic factor.
AB  - Brain-derived neurotrophic factor (BDNF) promotes the survival of various
      neuronal populations and thus shows potential in the treatment of
      neurodegenerative disease. However, BDNF is not pharmacokinetically optimal for
      use as a therapeutic agent. As a step toward the development of low-molecular
      weight BDNF-like drugs, we have designed a series of small, conformationally
      constrained peptides of various sizes using the three-dimensional structure of
      BDNF derived by homology modeling as a template. When tested in cultures of
      embryonic chick sensory neurons the peptides produced concentration-dependent
      inhibition of BDNF-mediated neuronal survival and caused both a rightward shift
      and depression of the maximum of the BDNF concentration-response curve. The
      compounds had no effect on the survival response to nerve growth factor and were
      without intrinsic trophic or toxic effects when added to cultures alone. With the
      aid of pharmacodynamic simulations we demonstrated that the inhibitory activity
      of the active peptides is consistent with them acting as competitive antagonists
      of BDNF for its high-affinity receptor, trkB. An alanine scan of the largest
      peptide identified several residues important in mediating the inhibitory action
      of the peptides. We intend to use the data from these studies to develop small
      peptidic BDNF-like agonists.

PMID- 9523591
TI  - Stimulation of muscarinic receptors induces expression of individual fos and jun
      genes through different transduction pathways.
AB  - The transduction pathways coupling muscarinic receptors to induction of fos and
      jun genes were investigated in neuroblastoma SH-SY5Y cells. Stimulation with
      carbachol induced expression of c-fos, fosB, c-jun, junB, and junD. This effect
      was abolished by pretreatment with atropine, indicating an involvement of
      muscarinic receptors. These genes were also induced by activation of protein
      kinase C with phorbol ester or by elevating the intracellular Ca2+ concentration
      with a Ca2+ ionophore. The Ca2+ effect was inhibited by KN-62, suggesting an
      induction through Ca2+/calmodulin-dependent kinase II. Inhibition of protein
      kinase C with GF109203X suppressed the carbachol-stimulated increase in mRNA
      levels of c-fos, fosB, and junB by approximately 70% but had only minor effects
      on the expression of c-jun and junD. On the other hand, preincubation with KN-62
      attenuated the carbachol-induced increase in c-jun and junD expression by 70% but
      had no effect on c-fos, fosB, and junB mRNA levels. Simultaneous inhibition of
      both protein kinase C and Ca2+/calmodulin-dependent kinase II completely
      abolished the carbachol-stimulated expression of c-jun and junD, but c-fos, fosB,
      and junB were still expressed to a certain extent under this condition.
      Comparison of the inhibitory effects of GF109203X and Go 6976 suggests the
      involvement of classical protein kinase C isozymes in muscarinic receptor
      stimulated expression of fos and jun genes. These results demonstrate that the
      muscarinic receptor-induced expression of individual fos and jun genes is
      regulated via different pathways, primarily protein kinase C or Ca2+/calmodulin
      dependent kinase II.

PMID- 9523593
TI  - Somatostatin potently stimulates in vivo striatal dopamine and gamma-aminobutyric
      acid release by a glutamate-dependent action.
AB  - We have used in vivo microdialysis in anaesthetised rats to investigate whether
      somatostatin (SRIF) can play a neuromodulatory role in the striatum. When 100 nM
      SRIF was retrodialysed for 15 min, it increased concentrations of dopamine (DA)
      by 28-fold, gamma-aminobutyric acid (GABA) by eightfold, and glutamate (Glu) by
      sixfold as well as those of aspartate (Asp) and taurine (Tau). These effects were
      both calcium- and tetrodotoxin-sensitive. Lower (10 or 50 nM) and higher (1
      microM) SRIF concentrations were less effective. Rapid sampling showed that
      whereas Asp and Glu concentrations were raised for 3 min at the start of 15-min
      SRIF infusions, those of DA were increased for 12 min. A second 15-min
      application of 100 nM SRIF given 135 min after the first application failed to
      increase transmitter release. An NMDA receptor antagonist, 2-amino-5
      phosphonopentanoic acid (200 microM), blocked SRIF (100 nM)-evoked Asp, Glu, Tau,
      and GABA release and reduced that of DA. An alpha-amino-3-hydroxy-5
      methylisoxazole-4-propionic acid (AMPA)/kainate antagonist, 6,7
      dinitroquinoxaline-2,3-dione (100 microM), blocked SRIF-induced DA and Tau
      release and reduced that of Asp, Glu, and GABA. These results show that SRIF
      increases DA, Glu, Asp, GABA, and Tau release in the rat striatum and suggest
      that its actions on DA and GABA release are mainly mediated through increased
      excitatory amino acid release.

PMID- 9523592
TI  - Biotransformation of L-DOPA to dopamine in the substantia nigra of freely moving
      rats: effect of dopamine receptor agonists and antagonists.
AB  - We investigated the effects of continuous intranigral perfusion of dopamine D1
      and D2 receptor agonists and antagonists on the biotransformation of locally
      applied L-DOPA to dopamine in the substantia nigra of freely moving rats by means
      of in vivo microdialysis. The "dual-probe" mode was used to monitor
      simultaneously changes in extracellular dopamine levels in the substantia nigra
      and the ipsilateral striatum. Intranigral perfusion of 10 microM L-DOPA for 20
      min induced a significant 180-fold increase in extracellular nigral dopamine
      level. No effect of the intranigral L-DOPA administration was observed on
      dopamine levels in the ipsilateral striatum, suggesting a tight control of
      extracellular dopamine in the striatum after enhanced nigral dopamine levels.
      Continuous nigral infusion with the D1 receptor agonist CY 208243 (10 microM) and
      with the D2 receptor agonist quinpirole at 10 microM (a nonselective
      concentration) attenuated the L-DOPA-induced increase in dopamine in the
      substantia nigra by 85 and 75%, respectively. However, perfusion of the
      substantia nigra with a lower concentration of quinpirole (1 microM) and the D1
      antagonist SCH 23390 (10 microM) did not affect the nigral L-DOPA
      biotransformation. The D2 antagonist (-)-sulpiride (10 microM) also attenuated
      the L-DOPA-induced dopamine release in the substantia nigra to approximately 10%
      of that of the control experiments. We confirm that there is an important
      biotransformation of L-DOPA to dopamine in the substantia nigra. The high
      concentrations of dopamine formed after L-DOPA administration may be the cause of
      dyskinesias or further oxidative stress in Parkinson's disease. Simultaneous
      administration of D1 receptor agonists with L-DOPA attenuates the
      biotransformation of L-DOPA to dopamine in the substantia nigra. The observed
      effects could occur via changes in nigral GABA release that in turn influence the
      firing rate of the nigral dopaminergic neurons.

PMID- 9523594
TI  - Histamine H1 receptor antagonists produce increases in extracellular
      acetylcholine in rat frontal cortex and hippocampus.
AB  - Lesions of the neuronal histaminergic system or pharmacological blockade of
      histamine receptors, e.g., with histamine H1 receptor antagonists, can enhance
      the performance of rats in several tests of learning and memory. The underlying
      neuronal systems that mediate these behavioral effects are not known. Here, we
      examined the effects of treatment with histamine H1 antagonists on extracellular
      levels of acetylcholine (ACh) in adult rats anesthetized with urethane (1.25
      g/kg). ACh was quantified using in vivo microdialysis and HPLC with
      electrochemical detection. Basal levels of ACh in the frontal cortex and
      hippocampus were in the range of 0.54 +/- 0.13 and 0.96 +/- 0.17 pmol/20 min,
      respectively. Injection (intraperitoneally) of saline did not produce significant
      increases in ACh levels, even though there was a slight and gradual increase in
      cortical ACh levels throughout the course of the experiments (up to 4 h after an
      injection). Administration of the H1 receptor antagonist chlorpheniramine
      (intraperitoneally) produced a dose-dependent increase of cortical ACh levels to
      a maximum of 260, 280, and 570% of baseline values after doses of 5, 10, and 20
      mg/kg, respectively. In the hippocampus, ACh content increased to a maximum of
      approximately 600% of baseline levels after chlorpheniramine administration (20
      mg/kg, i.p.). Administration of the H1 antagonist pyrilamine (intraperitoneally)
      increased cortical ACh content to a maximum of 300 and 500%, whereas hippocampal
      ACh levels increased to 215 and 280% after doses of 10 and 20 mg/kg,
      respectively. In an additional experiment using nonanesthetized, freely moving
      rats, cortical ACh content showed a moderate increase (to 190%) after saline
      injections (intraperitoneally) and a much higher increase (to 370%) after
      chlorpheniramine treatment (20 mg/kg, i.p.). These data suggest that cortical and
      hippocampal levels of ACh can be effectively modulated by systemic treatment with
      histamine H1 antagonists. The increases in ACh levels produced by H1 antagonists
      may suggest that some histaminergic receptors exert an inhibitory influence over
      central ACh levels. The enhanced availability of ACh in the forebrain may
      contribute to the behavioral effects observed with H1 antagonist treatment.

PMID- 9523595
TI  - Murine glial cells regenerate NAD, after peroxide-induced depletion, using either
      nicotinic acid, nicotinamide, or quinolinic acid as substrates.
AB  - The potential for regeneration of intracellular pyridine nucleotide levels from
      different precursors, after peroxide-induced NAD depletion, in cultured glial
      cells was investigated. Cultured murine glial cells showed a decrease in
      intracellular NAD levels of >40% after treatment with H2O2 (100 microM). Removal
      of the H2O2 followed by a 2-h incubation did not result in NAD recovery in the
      absence of precursors. However, NAD levels increased significantly in these cells
      after the following substrate additions, at minimum effective concentrations of 1
      mM for quinolinic acid (QUIN), 500 microM for nicotinamide, and 2 microM for
      nicotinic acid. The regeneration of significant amounts of NAD from nicotinic
      acid at doses 250 and 500 times lower than either nicotinamide or QUIN indicates
      a preferred route for NAD biosynthesis in glial cells in vitro, probably via
      nicotinic acid phosphoribosylation.

PMID- 9523596
TI  - Activation of p38MAPK in microglia after ischemia.
AB  - p38MAPK has been implicated in the regulation of proinflammatory cytokines and
      apoptosis in vitro. To understand its role in neurodegeneration, we determined
      the time course and localization of the dually phosphorylated active form of
      p38MAPK in hippocampus after global forebrain ischemia. Phosphorylated p38MAPK
      and mitogen-activated protein kinase-activated protein 2 activity increased over
      4 days after ischemia. Phosphorylated p38MAPK immunoreactivity was observed in
      microglia in regions adjacent to, but not in, the dying CA1 neurons. In contrast,
      neither c-Jun N-terminal kinase 1 nor p42/p44MAPK activity was altered after
      ischemia. These results provide the first evidence for localization of activated
      p38MAPK in the CNS and support a role for p38MAPK in the microglial response to
      stress.

PMID- 9523597
TI  - Lithium increases tyrosine hydroxylase levels both in vivo and in vitro.
AB  - Lithium, a simple monovalent cation, is the mainstay in the treatment of manic
      depressive illness, but despite extensive research, its mechanism of action
      remains to be elucidated. Because lithium requires chronic administration for
      therapeutic efficacy and because its beneficial effects last well beyond its
      discontinuation, it has been postulated that lithium may exert major effects at
      the genomic level. We have previously shown that lithium, at therapeutically
      relevant concentrations, increases gene expression through the activator protein
      1 (AP-1) transcription factor pathway in vitro. In the present study, we have
      sought to determine if lithium also increases the expression of endogenous genes
      known to be regulated by AP-1 and have therefore investigated the effects of
      lithium on tyrosine hydroxylase (TH) levels. Male Wistar rats were treated with
      LiCl for 9 days (subacute) or 4 weeks (chronic), and TH levels were measured in
      frontal cortex, hippocampus, and striatum using immunoblotting. Chronic (but not
      subacute) lithium treatment resulted in significant increases in TH levels in rat
      frontal cortex, hippocampus, and striatum. Lithium (1 mM) also increased TH
      levels in human SH-SY5Y neuroblastoma cells in vitro, indicating that lithium
      increases TH levels in both rodent and human tissues, likely via a direct
      cellular effect. These effects are compatible with (but likely not exclusively
      due to) an effect on the DNA binding of the 12-O-tetradecanoylphorbol 13-acetate
      response element to the AP-1 family of transcription factors.

PMID- 9523598
TI  - Effects of human type 1alpha metabotropic glutamate receptor expression level on
      phosphoinositide and Ca2+ signalling in an inducible cell expression system.
AB  - Stable expression of the human type 1alpha metabotropic glutamate (mGlu 1alpha)
      receptor was achieved in Chinese hamster ovary cells using an isopropyl-beta-D
      thiogalactoside (IPTG)-repressible expression system. Treatment of the cells with
      IPTG resulted in a time- and concentration-dependent induction of receptor
      expression. Maximal expression was obtained after treatment of the cells with 100
      microM IPTG for 20 h, leading to a marked increase in receptor immunoreactivity
      detected by western blot, >30-fold stimulation of 3H-labelled inositol phosphate
      (3H-InsP) production, and a robust increase in intracellular calcium
      concentration in single cells after stimulation with 20 microM quisqualate. The
      basal level of 3H-InsP accumulation in cells induced with IPTG was increased by
      two- to threefold as compared with control cells; however, this basal activity
      was found to be dependent on glutamate released by the cells into the incubation
      medium. Following IPTG treatment, stable expression of the mGlu 1alpha receptor
      was maintained for at least 1 week. Taken together, these results clearly
      indicate the advantages of working with an inducible expression system when
      studying the biochemical and pharmacological properties of the human mGlu 1alpha
      receptor in transfected cells.

PMID- 9523599
TI  - Physicians for Peace.

PMID- 9523600
TI  - Use of the balloon dissector in minimally invasive aesthetic and reconstructive
      surgery.
AB  - The use of minimally invasive surgery continues to evolve in all fields of
      surgery with new developments in techniques and instrumentation. One instrument
      that has evolved and become useful in the field of plastic surgery is the balloon
      dissector. The purpose of this paper is to examine the role of the balloon
      dissector in minimally invasive aesthetic and reconstructive plastic surgery. We
      define the concept of the fascial cleft-the loose areolar space between fascial
      linings. In addition, the balloon dissector and its use is described. The optical
      cavity created by the balloon dissector device is discussed, along with the two
      techniques used to maintain the optical cavity, and manual retraction and carbon
      dioxide insufflation. The application of the balloon dissector in various regions
      of the body is discussed along with its use in free tissue transfers. Three
      patients are presented to illustrate the application of the balloon dissector.

PMID- 9523601
TI  - Bridge narrowing in ethnic noses.
AB  - In certain ethnic noses with a relative lack of dorsal projection, patients often
      request a narrowed appearance on frontal view. There is little debate about the
      benefits of dorsal augmentation, but considerable disagreement about concomitant
      osteotomies. In a series of six African-American and Asian rhinoplasties, the
      author has addressed the wide-bridge appearance with dorsal augmentation alone,
      without osteotomies. Gore-Tex or cartilage was used for the augmentation. All
      patients were satisfied with the apparent bridge narrowing on frontal view.

PMID- 9523602
TI  - A controlled subatmospheric pressure dressing increases the rate of skin graft
      donor site reepithelialization.
AB  - The ability to increase the rate of skin graft donor site reepithelialization
      significantly in a cost-effective manner has important implications for the
      patient undergoing major reconstructive procedures. In this study the effect of
      externally applied reduced pressure (the V.A.C.) on the rate of healing of donor
      site wounds was initially investigated using a porcine model (N = 4), then
      repeated on humans (N = 10). Split-thickness skin grafts were harvested from the
      backs of pigs using standard technique. Half of the donor sites were treated with
      subatmospheric pressure (125 mmHg) and half were treated with an OpSite dressing.
      Biopsies taken every 48 hours demonstrated that sites exposed to reduced pressure
      healed at a much faster rate than sites treated with a standard occlusive
      dressing. Similarly, donor sites in humans reepithelialized faster in 7 of 10
      patients, the rate was the same in 2 of 10 patients, and OpSite was faster in 1
      of 10 patients. We believe this technology has the potential to be a relatively
      simple and cost-efficient method for increasing the rate of donor site healing.

PMID- 9523603
TI  - Use of pedicled flaps and tissue expanders to reconstruct burn scars of the skin
      of the anterior abdomen and chest.
AB  - Extensive scarring of the skin of the abdomen and chest is sometimes encountered
      postburn. It is possible to excise the burn scar serially and replace it with
      unburned skin from areas such as the lower abdomen by means of various
      advancement flaps. Expanders may be inserted to facilitate coverage as indicated.
      We report 9 patients (3 males and 6 females) in whom such staged procedures were
      carried out. Original burn size ranged from 4% to 52%, with a mean total body
      surface area of 23.8%. No major complications or blood loss requiring transfusion
      were encountered.

PMID- 9523604
TI  - Design-enhanced breast reduction: an approach for very large, very ptotic breasts
      without a vertical incision.
AB  - Breast reduction and mastopexy have been performed with a number of techniques.
      Due to problems encountered with prior procedures (such as fat necrosis, skin and
      nipple necrosis, decreased nipple sensitivity, shaping difficulties, and
      bleeding), we have changed our approach to breast reduction and mastopexy. Eleven
      initial patients have been operated with a design-enhanced procedure that
      emphasizes (1) a wide-based, glandular deepithelialized pedicle; (2) an attempt
      to preserve the fourth intercostal nerve; (3) adequate vertical-dimension skin
      excision leaving no vertical scar; (4) mesial advancement of thick, superior skin
      flaps; and (5) administration of dilute lidocaine/epinephrine solution. We have
      been pleased with our results and recommended this technique as our procedure of
      choice for patients with very large, very ptotic breasts.

PMID- 9523605
TI  - Reduction mammaplasty using the inferior pedicle technique.
AB  - A retrospective study of 350 reduction mammaplasties by the inferior pedicle
      technique performed over a 3-year period allows a critical evaluation of
      postoperative complications and patient satisfaction. The procedure can be done
      in a timely manner on an outpatient basis and is applicable to breasts of
      different shapes and sizes. The rate of postoperative complications (5%) was
      comparable with previous studies. Patient satisfaction was high (98%), with near
      total relief of preoperative symptoms. Concern about the resultant scars was low
      (2%) when the incisions followed the natural contour of the breast.

PMID- 9523606
TI  - Treatment of adolescent gynecomastia using a bipedicle technique.
AB  - Many methods have been described for the treatment of gynecomastia. Eleven
      adolescent boys have been managed with a bipedicle technique. These patients were
      evaluated for nipple-areolar viability, scarring, patient satisfaction, and
      hematoma or seroma formation. The pedicles providing blood supply to the nipple
      areolar complex are reliable and are derived from the dermis and glandular breast
      tissue, thus minimizing nipple-areolar necrosis and hypopigmentation as a
      complication of the procedure. A periareolar incision provides adequate exposure
      for safe dissection and excision of the breast tissue, and facilitates reduction
      in the complex if needed. Good to excellent results were reported in all 11
      patients at 2 weeks to 13 months of follow-up. There was no evidence of nipple
      areolar necrosis and only one case of postoperative seroma formation. This
      approach utilizes a safe and reliable method of breast reduction that is
      particularly effective in the male adolescent group.

PMID- 9523607
TI  - Microcirculatory studies of frostbite injury.
AB  - Frostbite represents a spectrum of injury ranging from irreversible cellular
      destruction to reversible changes seen after rewarming. These changes include
      increases in tissue edema, circulatory stasis, and progressive thrombosis leading
      to further tissue necrosis. For this reason, it is often difficult at the time of
      surgical debridement to determine the extent of frostbite injury. This delayed
      tissue injury is similar to that seen in muscle during ischemia/reperfusion
      injury. Muscle that initially appears viable on reperfusion may subsequently
      necrose due to collapse of the microcirculation. Adherent neutrophils have been
      specifically cited as important components in ischemia/reperfusion injury and
      have also been suggested to play a role in frostbite injury. We have used an
      intravital microscopic muscle preparation to study microcirculatory changes
      carefully in frostbite injury during rewarming. The right gracilis muscle of male
      Wistar rats is dissected free from its primary vascular pedicle and the rat is
      positioned on a specially constructed microsurgical stage. Temperature changes of
      the muscle are recorded. The prepared axial pattern flap is transilluminated with
      a microscope and projected on a video screen, allowing measurement of arteriolar
      diameters and changes in the numbers of stuck and rolling neutrophils before
      frostbite, during rewarming, and for several hours later. Cold silicone oil is
      used to freeze the muscle to -5+/-2 degrees C in 2 to 3 minutes and to hold this
      temperature for 5 minutes. The muscle is rewarmed with 42 degrees C normal saline
      placed directly on the muscle surface. Baseline vessel diameter and leukocyte
      counts in 100-mm segments of the microvasculature are recorded as well as at 5,
      15, and 30 minutes, and at 1, 2, and 3 hours postrewarming of frozen muscle.
      Observations from our initial 11 animals show that reperfusion of the muscle
      following freezing is varied temporally and spatially, with circulation to most
      vascular segments restored 5 to 10 minutes after rewarming. In 9 of 11 animals we
      observed the shedding of "white clots" in small arterioles and venules occurring
      as soon as 5 minutes after thawing. In some instances shedding continued for as
      long as 1 hour after rewarming. Microvascular hemorrhage was widespread 1 hour
      following the thaw, but there was no significant increase in neutrophil adherence
      observed until 3 hours following rewarming. The exact nature of the vascular
      injury and the composition of the "white clots" are now being determined from
      ultrastructural studies. Blood flow in microcirculation stops during freezing,
      but small-vessel perfusion returns immediately on thawing. This suggests that the
      vascular architecture is maintained during the freezing and thawing. Unlike
      ischemia/reperfusion injury, neutrophil adhesion plays a smaller role in the
      early response to frostbite injury. The early microcirculatory observations seen
      after rewarming suggest progressive and severe perturbations in platelet function
      and fibrin formation that are significantly different from ischemia/reperfusion
      injury.

PMID- 9523608
TI  - Cold intolerance is not more common or disabling after digital replantation than
      after other treatment of compound digital injuries.
AB  - Cold intolerance is a common reason for disability after hand injury. In this
      study of posttraumatic cold intolerance, 20 patients with a history of digital
      replantation were matched with 20 control subjects who had not undergone
      replantation. The incidence and intensity of cold-related symptoms among patients
      in the two groups was investigated through the use of individual interviews and a
      grading scale for self-assessment of symptoms. The analysis of data indicates
      that although the pattern of symptoms may vary, the condition is neither more
      common nor more disabling among those who have undergone digital replantation.
      Cold intolerance after digital replantation seems, therefore, to be defined by
      the initial trauma and not by the subsequent reconstructive surgery.

PMID- 9523609
TI  - Portable fluoroscopy in the management of zygomatic arch fractures.
AB  - Operative methods that do not allow intraoperative visualization of the fracture
      fragments in patients with isolated zygomatic arch fractures often result in
      inadequate reduction. This article describes a technique using a portable,
      surgeon-operated fluoroscopic machine that can be used preoperatively,
      intraoperatively, and postoperatively in patients with isolated zygomatic arch
      fractures. Using the portable fluoroscopic unit, reduction of isolated zygomatic
      arch fractures was performed in 9 consecutive patients over a period of 1.5
      years. Postoperative alignment was confirmed using computed tomography (CT).
      These CT images were compared with the fluoroscopic images in several of the
      patients. Eight of the nine fractures were reduced via an intraoral approach and
      one through a Gillies approach. All nine fractures were easily visualized and
      their reductions were confirmed with intraoperative dynamic visualization using a
      portable fluoroscopic unit. Postoperative CT revealed images of the reduction
      that were comparable with intraoperative and postoperative fluoroscopic images.
      The use of portable fluoroscopy intraoperatively allows for dynamic visualization
      of instrumentation and the immediate confirmation of the adequacy of fracture
      reduction. Moreover, this technique may eliminate the need for postoperative CT
      in isolated zygomatic arch fractures. Portable fluoroscopy may also have a place
      in the management of certain zygomatic complex fractures.

PMID- 9523610
TI  - Further clinical experience in permanent lip augmentation using autologous breast
      implant capsule.
AB  - Lip augmentation is a well tolerated procedure that can lead to a more youthful
      appearance. Autologous tissue offers the safest and most long lasting results.
      Recently, a new source of autologous tissue, breast implant capsule, was
      described in the performance of permanent lip augmentation. Long term data in
      thirteen patients is presented and documents persistence of volume enhancement of
      over one year postoperatively.

PMID- 9523611
TI  - Use of the free innervated dorsalis pedis tendocutaneous flap in composite hand
      reconstruction.
AB  - We used the free dorsalis pedis flap including the extensor digitorum longus or
      the extensor hallucis brevis, and/or the superficial peroneal nerve to
      reconstruct composite loss of skin and tendons on the dorsum of the hand. Between
      February 1992 and February 1996 we treated 7 patients with composite tissue loss
      on the dorsal hand caused by trauma or burn. Six men and 1 woman had an average
      age of 26 years (range, 19-42 years). Flap size ranged from 3 x 4 cm to 9.5 x 9
      cm. The follow-up period ranged from 10 to 44 months. At 1 week postoperatively,
      active flexion and passive extension commenced, and progressive resistance
      exercises were performed for an additional 5 weeks. Two-point discrimination of
      the transferred flaps averaged 25 mm. Recovery rates for range of motion of the
      metacarpophalangeal joints in the operated fingers ranged from 83% to 99%
      (average, 91.4%). All transferred flaps showed similar color match and skin
      texture compared with the normal skin of the hand. The advantages of this
      procedure are mass action reconstruction with multiple tendons, provision of
      similar skin texture, sensory reinnervation, one-stage operation, faster healing
      with less adhesion formation, and early mobilization. The disadvantages are donor
      site scarring and weak extension of the toe.

PMID- 9523612
TI  - The effects of preoperative irradiation on peripheral nerve regeneration.
AB  - The purpose of this study was to evaluate the effects of preoperative external
      cobalt60 beam irradiation on nerve regeneration. Ninety 250-g male Sprague-Dawley
      rats were studied. Peripheral nerve regeneration was measured by walking track
      analysis and histomorphology of the proximal, grafted, and distal nerve segments.
      Ninety animals were randomly assigned to one of five treatment groups, receiving
      a total fractionated dose of 30, 50, 70, and 90 Gy. Each animal received a 15-mm
      interposition nerve graft into the right posterior tibial nerve 6 weeks following
      completion of radiation therapy. The left leg served as a control. The remaining
      10 animals received a nerve isograft subjected to a single dose of 30 Gy prior to
      placement (group 5). Walking track analysis was performed monthly through 8
      months. At the conclusion of 120 and 240 days, sections of the proximal, grafted,
      and distal nerve were harvested, stained, and examined histomorphologically.
      Evaluation of the print length index demonstrated no statistical difference
      between our previously established nonirradiated controls, the irradiated groups,
      and the irradiated isograft group (group 5). The total number of axons per square
      millimeter was significantly decreased in the distal segment of all irradiated
      groups when compared with the controls. No statistical difference in number of
      axons per square millimeter was noted in the irradiated isograft group.
      Furthermore, no statistical difference was noted in the nerve fiber density
      between the control group, the preoperative irradiated groups, or the irradiated
      isograft group (group 5). Despite the reduction in myelinated regenerating
      fibers, no reduction in function was observed as measured by walking track
      analysis. Thus, immediate reconstruction of peripheral nerve defects in the face
      of preoperative irradiation may not be contraindicated.

PMID- 9523613
TI  - Closed septal osteotomy.
AB  - A technique is described that permits realignment of the bony septum
      (perpendicular plate of the ethmoid, vomer, and vomerine ridge). It involves a
      closed fracture of the bones by means of a large, long nasal speculum. Mere
      spreading of the septum fractures the bony septum, permitting reasonable, midline
      realignment in most patients. Spreading with the speculum also infractures the
      turbinates in many instances and thereby helps open up the airway even further.
      Of the 32 patients reviewed, it was found that the perpendicular plate and vomer
      could be fractured in 100% of patients. The vomerine ridge (premaxilla area), on
      the other hand, could only be fractured in 69%. Of the patients in whom fracture
      was possible, the bony septum was straightened dramatically in 82% of patients
      and improved greatly in 18% of patients.

PMID- 9523614
TI  - A new technique for aesthetic labia minora reduction.
AB  - A new technique has been developed to reduce the labia minora yet maintain the
      normal labial edge and color. Labia minora enlargement can be congenital or
      acquired by chronic irritation, exogenous androgenic hormones, and stretching
      with weights. This can cause inflammation, poor hygiene, interference with sexual
      intercourse, or intermittent urinary self-catheterization. Aesthetically,
      asymmetrical or enlarged labia minora causes self-consciousness sexually and when
      the subject wears tight pants. Previously labia minora reduction was performed by
      amputation of the protuberant segment and oversewing the edge. Now, rather than
      amputation, a wedge of protuberant labial tissue is excised and the labial edges
      are reapproximated. Four patients have undergone this aesthetic procedure with
      excellent results. No complications occurred. The new technique is relatively
      simple and can greatly enhance the patient's confidence.

PMID- 9523615
TI  - Customized composite reconstruction of extensive midfacial defects.
AB  - We describe the treatment of 2 patients with extensive midfacial defects by using
      a customized composite flap. Autogenous bone was transferred from the iliac
      crest, revascularized by the rectus muscle, and then transferred as a complete
      unit by microvascular technique to provide a vascularized bone graft to this area
      of difficult reconstruction. The bone was shaped and customized to fit the
      osseous defect. Although the rectus muscle was relatively bulky at the time of
      harvest, its hearty blood supply permitted trimming and contouring to fit the
      gap. This technique was based on the principles proposed previously by other
      authors regarding the vascularization of a free bone graft and its transfer as a
      composite flap. This technique requires more research and refinement, however
      this clinical demonstration shows the feasibility of revascularizing a composite
      flap and the extent to which this technique can be performed.

PMID- 9523616
TI  - Staged sequential reconstruction of a total lower lip, chin, and anterior
      mandibular defect.
AB  - The combination of a total lower lip, chin, and anterior mandibular defect
      following cancer resection is an extremely complex problem that requires a
      sequence of operations to optimize functional and aesthetic results. One patient
      is presented in whom the defect was reconstructed with a free fibular flap
      followed by a series of ancillary procedures using both modern and traditional
      techniques. At the time of tumor ablation, the through-and-through oromandibular
      defect was reconstructed with a fibular osteocutaneous flap. The lower lip and
      gingivolabial sulcus was reconstructed later with a tongue flap. Tissue expansion
      was subsequently used to replace the fibular skin with expanded submental hair
      bearing skin. A polyethylene implant was added later to the fibular bone for chin
      augmentation. Subsequently the lower lip was supported with a tendinous graft
      suspended to the anterior masseter bilaterally. Lastly, the vermilion border was
      elevated by removing a rim of the tongue flap and covering the secondary wound
      with a full-thickness skin graft. At the end of the reconstructive procedures,
      lip seal and oral aperture were good with no drooling and excellent speech.

PMID- 9523617
TI  - Bilateral facial lipoatrophy secondary to connective tissue panniculitis treated
      with two microsurgically transplanted latissimus dorsi muscles.
AB  - A case of bilateral facial atrophy diagnosed as atrophic connective tissue
      panniculitis is presented. Reconstruction of both cheeks was performed with two
      staged latissimus dorsi muscle flaps. The initial good result on the right cheek
      deteriorated as the disease continued to progress after surgery. The good result
      on the left cheek, however, remained stable. Detailed clinical examinations,
      laboratory analysis, and deep biopsies from the affected areas are important for
      accurate diagnosis. Reconstructive procedures should be delayed while the disease
      is still active.

PMID- 9523618
TI  - In defense of defense.

PMID- 9523619
TI  - Bye-bye close shave.

PMID- 9523620
TI  - Re: Saving face.

PMID- 9523621
TI  - Re: Psychological characteristics of women who undergo single and multiple
      cosmetic surgeries.

PMID- 9523622
TI  - Re: Functional reconstruction of total lower lip defects with a radial forearm
      free flap combined with a depressor anguli oris muscle transfer.

PMID- 9523623
TI  - Re: Mammographic visualization of a nonpalpable breast mass through a radiolucent
      breast implant.

PMID- 9523624
TI  - Nasoenteral feeding tube knot.

PMID- 9523625
TI  - Keloid fibroblasts from a Caucasian patient: are there differences in growth
      kinetics?

PMID- 9523626
TI  - Increasing efficiency in the operative field: knot tying, instrument ties, and
      locking the suture.

PMID- 9523627
TI  - Surgical considerations for improving elective incisions with emphasis on the
      breast, chest, and back.

PMID- 9523628
TI  - Health evaluation of black-faced impala (Aepyceros melampus petersi) using blood
      chemistry and serology.
AB  - As part of ongoing ecological studies of black-faced impala (Aepyceros melampus
      petersi) in northern Namibia, blood samples were collected and analyzed from 26
      animals captured for translocation in 1992. All animals appeared to be in good
      condition and no abnormality was noted during physical examination. Serum
      chemistry and mineral levels were measured and correlated with the results of
      bacterial and viral serology and were within the normal ranges for domestic
      ruminants. Antibody titers for infectious bovine rhinotracheitis and bovine viral
      diarrhea were detected. Serological tests for bluetongue, foot-and-mouth disease,
      rinderpest, parainfluenza 3, brucellosis, leptospirosis, and anaplasmosis were
      negative. Significant differences in disease prevalence were not found between
      sexes.

PMID- 9523629
TI  - Health evaluation of free-ranging and hand-reared macaws (Ara spp.) in Peru.
AB  - As part of ongoing ecological studies and reproduction enhancement efforts for
      macaws in southwestern Peru, a health survey of parent- and hand-reared scarlet
      macaws (Ara macao) and blue and gold macaws (Ara ararauna) was conducted in 1994.
      Thirty-three birds were examined during handling procedures, and blood samples
      were collected from 27 (9 parent reared, 18 hand reared) for laboratory analysis.
      All but one bird appeared to be in good condition, with no abnormality noted
      during physical examination. Hematology, plasma chemistries, and plasma vitamin
      and mineral levels were studied and correlated with the results of bacterial and
      viral serology. Positive antibody titers for Salmonella and psittacine
      herpesvirus were found. These diseases have the potential to affect wildlife
      population dynamics, and Salmonella may have public health significance.
      Serological tests for avian influenza, infectious laryngotracheitis,
      paramyxovirus-1, -2, -3, polyoma virus, chlamydiosis, and aspergillosis were
      negative. Differences in disease prevalence were found between rearing
      situations.

PMID- 9523630
TI  - The anatomy and perfusion of the renal portal system in the red-eared slider
      (Trachemys scripta elegans).
AB  - The anatomy of the renal portal system of the red-eared slider (Trachemys scripta
      elegans) is described, based on dissection of six double latex-injected specimens
      (three males, three females). The anatomy of these vessels, which had not
      previously been described in this species, was found not to differ significantly
      from the fundamental chelonian pattern. Fluoroscopic radioangiography revealed
      that venous blood returning from the hindlimbs flowed predominantly to the liver
      and bypassed the kidneys. Blood from the tail either flowed to the kidneys or
      bypassed them and flowed directly to the liver. A putative valve is described
      that governs venous blood flow from the caudal body to or around the kidneys.

PMID- 9523632
TI  - Hematology and clinical chemistry reference ranges for clinically normal, captive
      New Guinea snapping turtle (Elseya novaeguineae) and the effects of temperature,
      sex, and sample type.
AB  - Median values and confidence intervals for hematology and serum and plasma
      chemistry parameters were established for 29 male and female healthy New Guinea
      snapping turtles (Elseya novaeguineae) held at 24.5 degrees C and 30.0 degrees C.
      Creatine kinase, albumin, potassium, and phosphorus values were significantly
      higher at 24.5 degrees C than at 30.0 degrees C. Glucose, alkaline phosphatase,
      aspartate transaminase, alanine aminotransferase, total carbon dioxide, and
      chloride values were significantly higher at 30.0 degrees C than at 24.5 degrees
      C. Cholesterol and calcium values were significantly higher in females than in
      males. Hemoglobin, packed cell volume, and bilirubin were significantly higher in
      males than in females, and bile acid values were significantly higher in serum
      than in plasma.

PMID- 9523631
TI  - The effect of the renal portal system on pharmacokinetic parameters in the red
      eared slider (Trachemys scripta elegans).
AB  - The premise that drugs not be injected into the caudal body of reptiles because
      they will be carried by the renal portal system to the kidneys, where they may be
      nephrotoxic or rapidly excreted, was tested by comparing the pharmacokinetics of
      gentamicin (excreted via glomerular filtration in mammals) and carbenicillin
      (excreted partly via renal tubular secretion in mammals) following injection into
      the forelimb or hindlimb of red-eared sliders (Trachemys scripta elegans). Ten
      sliders received intramuscular gentamicin (10 mg/kg) in a forelimb (n = 5) or a
      hindlimb (n = 5), and plasma levels of the drug were assayed over time. Following
      drug clearance, the experiment was repeated with the site of injection reversed
      so that each animal acted as its own control. Another 10 sliders were similarly
      treated, using intramuscular carbenicillin (200 mg/kg). Injection site of
      gentamicin had no effect on any pharmacokinetic parameter (time to maximum plasma
      concentration, maximum plasma concentration, half-life, area under the curve,
      clearance, and volume of distribution). However, the area under the curve of
      plasma carbenicillin concentration vs. time was significantly lower following
      hindlimb injection, in comparison with forelimb injection, at 1, 4, and 8 hr,
      which may reflect reduced bioavailability of the drug, as would be expected with
      renal portal perfusion and tubular excretion on first pass through the kidney.
      This effect on carbenicillin likely is not clinically important because plasma
      levels remained above recommended minimum inhibitory concentrations. Because
      blood draining the caudal body of reptiles passes through the kidneys or the
      liver before reaching the central circulation, the effect on the pharmacokinetics
      of a drug injected in that region will vary with its renal or hepatic extraction
      rate. Generally, this effect is unlikely to be significant.

PMID- 9523633
TI  - Serum lipoprotein, thyroid hormone and resting cortisol levels in normal cheetahs
      (Acinonyx jubatus).
AB  - Blood obtained from 20 cheetahs (Acinonyx jubatus) during annual physical
      examinations was analyzed for serum lipid concentration, for lipoprotein
      distribution by agarose gel electrophoresis, and for thyroid hormone and resting
      cortisol levels by solid-phase radioimmunoassay to develop normal reference
      ranges.

PMID- 9523634
TI  - The impact of water temperature on core body temperature of North American river
      otters (Lutra canadensis) during simulated oil spill recovery washing protocols.
AB  - Ten North American river otters (Lutra canadensis) were anesthetized with Telazol
      and instrumented with ingestable radiotelemetry temperature sensors for measuring
      core body temperature. The otters were then subjected to a washing protocol to
      simulate rehabilitation following an oil spill contamination. This protocol
      consisted of a 30-min wash in a 1:16 dilution of dishwashing liquid using either
      cold (24 degrees C) water or water near baseline core body temperature (38.4
      degrees C), followed by a 30-min rinse with water of the same temperature,
      followed by 10 min of forced hot air drying. Core body temperatures of the otters
      washed in cold water fell at a median rate of 0.1 degrees C/min, whereas otters
      washed in warm water maintained stable core temperatures until the completion of
      the protocol, at which time their core temperatures began to drop at a similar
      rate. Core temperatures restabilized in both groups, and no statistical
      difference in core temperature between groups remained 180 min after initiation
      of the protocol. Efforts to examine the efficacy of supplemental squalene
      administration to speed the recovery of fur condition and waterproofing were
      unsuccessful because the washing protocol did not cause loss of coat
      waterproofing in 8 of the 10 subjects.

PMID- 9523635
TI  - Postanesthetic monitoring of core body temperature using telemetry in North
      American river otters (Lutra canadensis).
AB  - Remote thermal telemetry was performed on North American river otters (Lutra
      canadensis) during the 1995 North Carolina Wildlife Resources Commission Otter
      Restoration Project. Otters were anesthetized with either ketamine-midazolam (n =
      11) or tiletamine-zolazepam (n = 9) combinations. Based upon initial rectal
      temperatures, mild to moderate hyperthermia (39.4-40.5 degrees C) developed in
      five otters given ketamine-midazolam and three otters given tiletamine-zolazepam.
      Following anesthetic induction, each otter received an ingestible temperature
      transmitter. Dependent upon gastrointestinal transit time and transmitter battery
      life, core body temperature was monitored for up to 13.75 hr postanesthesia.
      Thermal telemetry revealed a gradual decline in core temperature in all otters
      after anesthetic recovery (30-60 min). Median core temperature stabilized
      subsequently within 0.3 degrees C of resting temperature (38.4 degrees C) 1.75 hr
      after initial injection in otters given tiletamine-zolazepam and 2.75 hr in
      otters given ketamine-midazolam. Minor fluctuations in body temperature (less
      than 1 degree C) occurred in most otters from 6 to 13.75 hr and were attributed
      to variations in physical activity.

PMID- 9523636
TI  - Tiletamine-zolazepam anesthesia in North American river otters (Lutra canadensis)
      and its partial antagonism with flumazenil.
AB  - North American river otters (Lutra canadensis) were anesthetized with tiletamine
      zolazepam or tiletamine-zolazepam-flumazenil combinations in cooperation with the
      North Carolina Wildlife Resources Commission Otter Restoration Project for
      evaluation of physiologic changes during anesthesia. Sixteen otters received
      tiletamine-zolazepam (4 mg/kg combined, i.m.) in 1994. Induction and recovery
      times were recorded and physiologic data (heart rate and rhythm, respiratory
      rate, rectal temperature, relative oxyhemoglobin saturation, and mean arterial
      blood pressure) were collected at 5-min intervals. Respiratory depression
      developed initially in all otters, and median relative oxyhemoglobin saturation
      remained below 90% for the first 15 min of anesthesia. Anesthetic induction with
      tiletamine-zolazepam was rapid and smooth, but recovery was prolonged (median =
      89 min) and characterized by persistent head motion. In 1995, flumazenil was
      evaluated as a partial antagonist for tiletamine-zolazepam anesthesia in otters.
      Sixteen otters were anesthetized with tiletamine-zolazepam (4 mg/kg combined,
      i.m.) and given flumazenil (1 mg per 25 mg of zolazepam) after 20 min. Flumazenil
      markedly shortened recovery time in all otters anesthetized with tiletamine
      zolazepam (median = 65 min) with no adverse effects.

PMID- 9523637
TI  - Predicting body weight from body measurements in Asian elephants (Elephas
      maximus).
AB  - Accurate estimates of body weight can be useful in the evaluations of feeding
      programs, nutritional status and general health, and in calculation of dose
      levels (such as for anesthesia)-thus providing a valuable tool for captive
      elephant management. We used body measurements of 75 Asian elephants (Elephas
      maximus) to predict body weight. Weight, heart girth, height at the withers, body
      length, and foot-pad circumference were measured. All possible linear regressions
      of weight on one, two, three, or four body measurements were calculated. The
      highest correlation with a single measurement was that between heart girth and
      weight (R2 = 0.90). The data were also divided into age groups (1-13, 18-28, 29
      39, and 40-57 yr), and all possible linear regressions were calculated for each
      group (there were no elephants aged 14-17 yr). Adding body length or pad
      circumference to heart girth resulted in a slight increase in R2. We conclude
      that body weight in Asian elephants can be predicted from body measurements and
      that heart girth is the best predictor. A second body measurement might improve
      predictive accuracy for some age groups.

PMID- 9523638
TI  - Analysis of urinary progesterone metabolites with behavioral correlation in
      Guenther's dik-dik (Madoqua guentheri).
AB  - Urine samples and behavioral data were collected from nine adult female
      Guenther's dik-dik (Madoqua guentheri) from September 1989-November 1992. The
      durations of predefined individual behaviors were recorded during focal sampling
      periods and ad libitum. Immunoreactive pregnanediol-3-glucuronide (PdG)
      concentration in dik-dik urine was determined by radioimmunoassay. The
      immunoreactive PdG radioimmunoassay was validated for use with dik-dik by
      determining parallelism [F(alpha=0.05,1,4) = 0.04) between a serially diluted PdG
      standard and serially diluted dik-dik urine. Behavioral estrus was manifested by
      lordosis. Eighty-nine percent of the estrous behavior occurred during or within 2
      days of the interluteal phase period, as delineated by immunoreactive PdG
      concentrations; thus, a high degree of correlation between hormone concentrations
      and behavioral data was observed. The mean (+/-SD) luteal phase, interluteal
      phase, and estrous cycle lengths were 14.4+/-5.5 days (range, 6-29 days; n = 50),
      6.6+/-5.1 days (range, 2-33 days; n = 50), and 20.2+/-6.6 days (range, 10-43
      days; n = 48), respectively. During the collection period, one animal conceived,
      with a gestation period of 170 days. Estrous cyclicity occurred throughout the
      year, with no evidence of seasonality. Cochromatography of pooled urine samples
      with radiolabeled PdG indicated that the major progesterone metabolite detected
      by the immunoreactive PdG antibody during luteal phase and pregnancy was not PdG.
      This is the first detailed description of female dik-dik reproductive endocrine
      activity.

PMID- 9523639
TI  - Cutaneous mycoses in chameleons caused by the Chrysosporium anamorph of
      Nannizziopsis vriesii (Apinis) Currah.
AB  - A dermatophyte-like fungus was isolated from skin biopsies of three different
      species of captive chameleon in which fungal elements had been observed by
      histologic examination. An adult Parson's chameleon (Chamaeleo parsonii)
      presented with vesicles that became crusty brown lesions on the limbs and body.
      Skin biopsies revealed fungal hyphae in the affected epidermis and underlying
      dermis. The lesions regressed fully after oral administration of itraconazole. An
      adult jewel chameleon (Chamaeleo lateralis) from the same private collection
      presented with localized black skin lesions and died while being treated with
      itraconazole. A pulmonary granuloma was also present in this chameleon at
      autopsy. Cultures obtained from skin and lung lesions yielded the same fungus. A
      third isolate was obtained from a skin biopsy of a Jackson's chameleon (Chamaeleo
      jacksoni) with deep ulcerative cutaneous lesions located at the base of the tail.
      The fungus, in all three cases, has been identified as the Chrysosporium anamorph
      of Nannizziopsis vriesii, a poorly known ascomycetous species recorded previously
      from the skin of a lizard and from soil, on the basis of its keratinolytic
      activity, resistance to cycloheximide, strongly restricted growth at 37 degrees
      C, formation of clavate or pyriform single-celled or two-celled aleurioconidia,
      and alternate and fission arthroconidia.

PMID- 9523640
TI  - A comparison of sampling methods for airborne fungal spores during an outbreak of
      aspergillosis in the forest aviary of the North Carolina Zoological Park.
AB  - An outbreak of aspergillosis with the death of six birds in the North Carolina
      Zoological Park R. J. Reynolds Forest Aviary in the spring of 1993 led to an
      investigation of the concentration of Aspergillus fumigatus spores in the air. No
      Aspergillus sp. was found in the facility through use of the drop plate method
      (gravitometric sampling) along with swab-sampling of selected surfaces within the
      exhibit and plating of food samples and nesting material onto petri dishes of
      nutrient media. A number factors that could stress the avian population were
      identified. These included excessive heat in the upper portion of the aviary due
      to the failure of an air handling system, a malfunctioning cooling tower, and
      large numbers of visitors to the facility (an average of 3,500/day). In addition,
      the outbreak occurred during a period of increased nesting behavior. Sampling of
      the fungal population of the air was conducted 1 year later, when no disease was
      noted, to compare the sensitivity of the commonly used drop plate method (open
      plates of nutrient media) with a volumetric impaction method (Andersen N-6 Air
      Sampler). The volumetric method delivered quantitative as well as qualitative
      data and exhibited more sensitivity for fungal spores of size similar to those of
      Aspergillus sp.

PMID- 9523642
TI  - Comparative rectal bacterial flora of four species of flying fox (Pteropus sp.).
AB  - The rectal anaerobic and aerobic bacterial flora of four species of flying foxes
      were determined and compared. Four bacterial species were found in > or = 1
      individual from each bat species at a significant (> or = 10%) level of the
      bacterial population: alpha-hemolytic Streptococcus sp. (41 of 56 bats),
      Enterococcus sp. (25/56), Escherichia coli (21/ 56), and group D Streptococcus
      sp., not Enterococcus sp. (9/56). Five other microbial species were also found in
      all four flying fox species, but at less significant percentages (found in at
      least one bat species, > or = 5% and < or = 10% of the recovered microbial
      population). These were nonhemolytic Streptococcus sp. (30/56), yeast (26/56),
      Corynebacterium sp. (25/56), Staphylococcus sp. (25/56), and Staphylococcus
      aureus (22/56). The majority of the species found were gram-positive, and only
      two obligate anaerobes, a Lactobacillus and a Bacteroides sp., were recovered
      from one bat.

PMID- 9523641
TI  - Hematologic and plasma biochemical reference values for three flying fox species
      (Pteropus sp.).
AB  - Reference hematologic and plasma biochemical values from island (Pteropus
      hypomelanus), Malaysian (P. vampyrus), and Rodriquez Island (P. rodricensis)
      flying foxes were determined. In comparison to other mammals, these bats had very
      low plasma cholesterol and urea levels, which may be related to diet. The
      predominant white blood cells observed in P. hypomelanus and P. vampyrus were
      lymphocytes, while in P. rodricensis they were neutrophils. Elevated plasma
      levels of calcium, phosphorus, and alkaline phosphatase observed in the juvenile
      P. hypomelanus were expected, given the greater osteogenic activity of growing
      animals. In P. hypomelanus, bilirubin levels were higher in juveniles than in
      adults, and cholesterol levels were higher in females than in males.

PMID- 9523643
TI  - Hyperlipidemia in four related male cheetahs (Acinonyx jubatus).
AB  - Hyperlipidemia was identified in an 11-yr-old male cheetah (Acinonyx jubatus) and
      three related 3-yr-old male cheetah littermates. Hyperlipidemia in these four
      cheetahs was characterized by hypertriglyceridemia and hypercholesterolemia. The
      mean percentages of chylomicron and beta-lipoproteins were greater (P < 0.05) and
      the mean percent of alpha-lipoproteins was lower (P < 0.05) than the respective
      means for a group of 20 nonhyperlipidemic and clinically normal cheetahs. The
      etiology of the hyperlipidemia in these four cheetahs was not determined.
      However, the older cheetah also had chronic renal insufficiency and a parathyroid
      adenoma, conditions that have been associated with hyperlipidemia.

PMID- 9523645
TI  - Pulmonary cryptococcoma and cryptococcal meningoencephalomyelitis in a king
      cheetah (Acinonyx jubatus).
AB  - A captive king cheetah (Acinonyx jubatus) was evaluated for a subacute onset of
      ataxia in all four limbs. The ataxia appeared to be spinal in origin, evidenced
      by apparent conscious proprioceptive deficits in all limbs, and there was no
      evidence of cerebellar involvement. Anesthesia was performed and survey spinal
      radiographs were normal. Cerebrospinal fluid analysis revealed an apparently
      sterile meningitis of unknown etiology. Although transient improvement was noted
      with glucocorticoid and antimicrobial therapy, the condition deteriorated
      subsequently and the animal became quadriparetic and paraplegic. Follow-up
      cerebrospinal fluid analysis and culture revealed the presence of Cryptococcus
      neoformans. Myelography demonstrated obstruction of the subarachnoid space at the
      level of the seventh cervical vertebra. Pathological examination following
      euthanasia revealed a solitary pulmonary cryptococcoma and confirmed cryptococcal
      meningoencephalomyelitis.

PMID- 9523644
TI  - Duodenal perforation in a cheetah (Acinonyx jubilatus).
AB  - An 11-yr-old female cheetah (Acinonyx jubilatus) from a privately owned breeding
      center for endangered species was referred for evaluation with a history of
      vomiting and depression of 10 days' duration. After anesthetic induction with
      tiletamine and zolazepam and anesthetic maintenance with isoflurane, a complete
      diagnostic workup was performed, including hematology, serum chemistry, and
      radiography. The clinical diagnosis was septic suppurative inflammation and
      hemorrhage in the abdomen, consistent with perforation or rupture of the
      gastrointestinal tract. An exploratory laparotomy showed a perforated duodenal
      ulcer, which was resected. Subsequent endoscopy revealed no further evidence of
      ulceration in the upper gastrointestinal tract. Biopsy of the ulcerated tissue
      collected from the duodenum revealed Gastrospirillum-like organisms. Histologic
      examination revealed widespread infiltration of lymphocytes and plasma cells into
      the lamina propria and submucosa. Intraepithelial leukocytes were present along
      with attenuation, erosion, and ulceration of the superficial epithelium. Fourteen
      days after surgery, this cheetah was returned to its breeding compound, and no
      subsequent vomiting has been observed for 4 yr.

PMID- 9523646
TI  - Fatal Toxoplasma gondii infection in golden lion tamarins (Leontopithecus rosalia
      rosalia).
AB  - Four of five golden lion tamarins (Leontopithecus rosalia rosalia) died after a
      brief period of illness 13 to 21 days following the consumption of a feral mouse
      by the group. Three of the four animals died within hours after being observed as
      clinically healthy. The fourth animal became weak, failed to respond to
      treatment, and died several hours after treatment. At necropsy, there were bands
      of serosal and mucosal hemorrhages of the intestines, and the lungs were mottled.
      Histologically, necrosis and acute inflammation associated with tachyzoites of
      Toxoplasma gondii were found in intestines, liver, heart, lung, and eyes. The
      communally consumed mouse was presumed to be the source of T. gondii infection in
      this exhibit. The surviving tamarin probably did not share food.

PMID- 9523647
TI  - Fatal Erysipelothrix rhusiopathiae septicemia in a captive Pacific white-sided
      dolphin (Lagenorhyncus obliquidens).
AB  - One male of a group of seven Pacific white-sided dolphins (Lagenorhynchus
      obliquidens) died after a brief period of nonspecific clinical signs. Four beluga
      whales (Delphinapterus leucas) and four harbor seals (Phoca vitulina) were
      managed in the same water system. Gross examination of the dolphin revealed only
      moderately enlarged mesenteric lymph nodes. Histopathology revealed small to
      massive numbers of gram-positive bacilli, usually intravascular, in all tissues.
      Bacteria were both extracellular and present in macrophages, monocytes, and
      neutrophils. Aerobic bacterial culture of lung, liver, kidney, and spleen yielded
      pure cultures of Erysipelothrix rhusiopathiae. Based on clinical course,
      histopathology, and bacteriology, a diagnosis of acute erysipelas septicemia was
      made. None of the other cetaceans or pinnipeds exhibited clinical signs.

PMID- 9523648
TI  - Small intestinal adeno-like virus in a mountain chameleon (Chameleo montium).
AB  - An adult male mountain chameleon (Chameleo montium), one of 92 individuals
      recently caught in the wild and transported, died after a 28-day history of
      anorexia. Gross examination revealed marked emaciation and enteric nematodiasis.
      Histopathologic examination of the small intestine revealed moderate numbers of
      enterocytes containing 2-15 micrometer-diameter round to ellipsoid, basophilic,
      intranuclear inclusions. Ultrastructurally, the inclusions consisted of
      crystalline arrays of hexagonal viral particles 67-76 nm in diameter with
      electron-dense cores. The viral particles were consistent with an adenovirus. No
      pathologic changes were associated with the adenoviral infection.

PMID- 9523649
TI  - Clinical challenge. Multiple primary rhabdomyosarcomas within the myocardium of a
      vulture.

PMID- 9523650
TI  - Fournier's gangrene.

PMID- 9523651
TI  - Lower moiety heminephroureterectomy in the duplex refluxing kidney: the accuracy
      of isotopic scintigraphy in functional assessment.
AB  - OBJECTIVE: To determine the accuracy of dimercaptosuccinic acid (DMSA)
      scintigraphy in assessing the differential function between upper and lower
      moieties of a refluxing duplex system. PATIENTS AND METHODS: Between 1990 and
      1996, 20 patients underwent lower moiety heminephroureterectomy. All patients had
      their differential renal function assessed by DMSA scintigraphy before and after
      surgery, the results being assessed by comparing the predicted and actual loss of
      renal function. RESULTS: The mean (SD, range) function attributed to the scarred
      lower moiety (predicted loss of function) was 4.3 (4.9, 0-14)%, which compared
      with an actual mean loss of function of 6.8 (5.1, +4 to -16)%. Thus the mean (SD,
      range) difference between the predicted and actual loss of renal function was 
      2.1 (3.2, +4 to -8)%. CONCLUSION: DMSA scintigraphy provides an accurate
      assessment of the differential renal function between upper and lower moieties in
      a duplex system. The decision to proceed to lower moiety heminephroureterectomy
      can be logically based on the information gained from DMSA scintigraphy.

PMID- 9523652
TI  - The role of power Doppler ultrasonography in the diagnosis of acute
      pyelonephritis.
AB  - OBJECTIVE: To assess the ability of power Doppler ultrasonography (PDU) to detect
      acute pyelonephritis and to compare the findings from PDU with those from
      enhanced computed tomography (CT). PATIENTS AND METHODS: Eleven patients (mean
      age 18.5 years, range 5-37) admitted to hospital with a clinical diagnosis of
      pyelonephritis were assessed with PDU and enhanced CT. the latter providing the
      reference method. RESULTS: The imaging studies showed normal findings in three
      patients; a single focus of pyelonephritis was detected by CT in six, whereas a
      matching defect was detected on PDU in five, with PDU failing to detect an
      infective focus in one. Multifocal diffuse pyelonephritis was diagnosed correctly
      by enhanced CT and PDU in two patients. CONCLUSION: Power Doppler ultrasonography
      had an overall sensitivity of 88% and complete specificity in the evaluation of
      patients with acute pyelonephritis.

PMID- 9523653
TI  - Prevalence of lower urinary tract symptoms in Finnish men: a population-based
      study.
AB  - OBJECTIVE: To determine the prevalence of lower urinary tract symptoms (LUTS) in
      Finnish men, using a population-based cross-sectional survey. SUBJECTS AND
      METHODS: In 1994, a modified Danish prostatic symptom score system (DAN-PSS-1)
      questionnaire on the occurrence and severity of LUTS was mailed to all men (3143)
      born in 1924, 1934 or 1944 living in the city of Tampere or 11 rural and semi
      rural municipalities in the same county. RESULTS: After exclusions, 68% of the
      men were ultimately included in the study. LUTS were common and increased with
      age so that the prevalence of at least one symptom was 89% in the whole
      population (84%) among 50-year-old, 91% among 60-year-old and 94% among 70-year
      old men). Most of the symptoms were mild, with post-micturition dribbling and
      nocturia the most prevalent symptoms, and stress incontinence the least
      prevalent. CONCLUSIONS: The high incidence of LUTS may indicate a high prevalence
      of benign prostatic enlargement secondary to benign prostatic hyperplasia, but
      other causes are also involved. With the increase in the mean age of the general
      population, the number of individuals with LUTS is likely to increase and must be
      considered when resources are planned for medical care.

PMID- 9523654
TI  - Changes in white blood cell counts in men undergoing thrice-weekly prostatic
      massage, microbial diagnosis and antimicrobial therapy for genitourinary
      complaints.
AB  - OBJECTIVE: To report changes in the white blood cell (WBC) counts in expressed
      prostatic secretions (EPS) in men with pelvic symptoms undergoing thrice-weekly
      prostatic massage combined with antimicrobial therapy. PATIENTS AND METHODS: The
      study comprised a retrospective analysis of the records of 35 patients (mean age
      45.3 years, range 28-70, SD, 12.03) with pelvic pain, pain in the lower back,
      obstructive urinary symptoms, irritative urinary symptoms, or sexual dysfunction,
      who had undergone the same diagnosis and treatment protocol in a genitourinary
      clinic in Manila, Philippines, from September 1992 to September 1995. RESULTS:
      EPS were obtained 347 times in 35 patients (median 9 times per patient, range 6
      16). In 26 of the 35 (74%) patients the WBC count in the EPS was < 10 per oil
      immersion field (OIF, x1000) at the first prostatic massage. In 34 of 35 (97%)
      patients the WBC count rose to > or = 10 as prostatic massage continued on a
      thrice-weekly schedule. The mean (range, SD) initial WBC count in the EPS was 8.4
      (1-48, 8.43) and the maximum was 40.9 (6-60, 19.05); the difference between these
      values was 32.5 (3-57, 18.78; 95% confidence interval 26.1-40.1) and the
      difference was statistically significant (paired t-test, P < 0.001). CONCLUSIONS:
      The classification of patients into those with prostatodynia or prostatitis based
      on one EPS examination is misleading and thrice-weekly massage of the prostate is
      better than a single collection of EPS to obtain the most purulent sample for
      Gram staining and culture.

PMID- 9523655
TI  - Microwave thermotherapy: a long-term follow-up of 67 patients from a single
      centre.
AB  - OBJECTIVE: To determine the long-term therapeutic value of transurethral
      microwave thermotherapy (TUMT) in the treatment of bladder outflow obstruction
      secondary to benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: A total of
      67 patients with BPH, assessed using symptom scores and measurements of urinary
      flow rate, underwent TUMT using the Leo Microthermer system (Laser Electro Optics
      Ltd, London, UK) between October 1990 and June 1992. Follow-up information was
      obtained on 60 patients (90%). If they had undergone no further treatment for
      their BPH, they were re-assessed with symptom scores and measurements of flow
      rate. RESULTS: The mean follow-up was 52.4 months; eight of the 6 7 patients had
      died and seven were lost to follow-up. Sixteen of the remaining 52 (31%) had
      undergone another treatment for BPH; one patient developed prostatitis and one
      developed localized carcinoma of the prostate. Thirty-four patients had had no
      further treatment, 29 of whom attended for assessment. In these patients, a
      statistically significant improvement in both the symptom score and flow rate was
      maintained at 4 years. No patients developed retrograde ejaculation. CONCLUSION:
      This is the first study to report a follow-up of at least 4 years after TUMT with
      any device. Treatment with the Leo Microthermer provided at least a 50%
      symptomatic improvement in 16 of 50 patients treated at 4 years. However, 30% of
      the patients needed further treatment for their BPH. TUMT is safe and effective
      in patients not wanting anaesthesia and in young patients concerned about
      retrograde ejaculation.

PMID- 9523657
TI  - Evaluation of histological structure and its effect on the distribution of alpha1
      adrenoceptors in human benign prostatic hyperplasia.
AB  - OBJECTIVE: To evaluate the histological structure of benign prostatic hyperplasia
      (BPH) and its relationship with the density of alpha1-adrenoceptors in smooth
      muscle. MATERIALS AND METHODS: Specimens from hyperplastic tissues obtained from
      14 patients with BPH were evaluated for the density of alpha1-adrenoceptors in
      smooth muscle using autoradiography, Mallory-Azan staining and computer-assisted
      image analyses. The binding of [3H] tamsulosin (a selective alpha1-blocker) and
      the ratio of smooth muscle area was calculated, and the density of alpha1
      adrenoceptors per area of smooth muscle determined by dividing the degree of
      binding by the ratio of smooth muscle to total area. RESULTS: There was a
      significant difference between the ratio of smooth muscle area in the
      hyperplastic acinar nodule and the surrounding stroma (P < 0.01). The density of
      alpha1-adrenoceptor per smooth muscle area was significantly higher in the
      hyperplastic acinar nodule than in the surrounding stroma (P < 0.05). There was
      no correlation between prostatic weight and the ratio of smooth muscle area or
      the density of alpha1-adrenoceptors in each region. CONCLUSION: The distribution
      of alpha1-adrenoceptors on smooth muscle differed with histological structure;
      both the histological conformation and the difference in the distribution of
      alpha1-adrenoceptors could affect urethral obstruction in BPH.

PMID- 9523656
TI  - Placebo therapy of benign prostatic hyperplasia: a 25-month study. Canadian
      PROSPECT Study Group.
AB  - OBJECTIVE: To analyse the efficacy, correlations and adverse-event profile of
      placebo therapy from the initial placebo run-in period to beyond 2 years of
      treatment. PATIENTS AND METHODS: The effects of placebo therapy on prostate size,
      maximum urinary flow rate (Qmax) and symptoms were analysed, and adverse drug
      experiences documented, for a period of 25 months in 303 patients randomized to
      the placebo arm of a controlled trial evaluating finasteride in the treatment of
      BPH (the Canadian PROSPECT study). RESULTS: For all variables, the values during
      follow-up were significantly different from baseline (P < or = 0.001).
      Transrectal ultrasonography confirmed a progressive increase in prostate volume
      over 25 months (+8.4%) but Qmax improved for the first 5 months (to 1.4 mL/s over
      baseline) and remained 1.0 mL/s more than baseline at 25 months. The total
      symptom score improved by -2.9 points in the first 2 months on placebo and was
      ultimately 2.3 points below baseline at 25 months. The extent of the placebo
      response for symptoms (r=0.08, P=.180) and Qmax (r=0.04, P=0.550) was independent
      of age, but the response correlated with the initial severity of symptoms (r= 
      0.394, P < or = 0.001) and initial Qmax (r= -0.134, P=0.023). Patients with a
      prostate of < or = 40 mL had a clinically more important placebo response than
      those with larger prostates. In all, 246 patients (81.2%) reported adverse events
      thought to be secondary to placebo therapy. The most common complaint was
      urogenital (40.3%), specifically impotence (6.3%) and decreased libido (6.3%);
      13.2% of patients discontinued placebo therapy because of significant adverse
      reactions. CONCLUSIONS: Placebo therapy rapidly produces a significant
      improvement in Qmax and symptoms of BPH but also causes clinically important
      adverse effects. The beneficial effect fades but remains after 2 years.

PMID- 9523658
TI  - Improvements in the efficiency of care after implementing a clinical-care pathway
      for transurethral prostatectomy.
AB  - OBJECTIVE: To investigate the efficiency of care, length of hospital stay and
      admission charges after implementing a clinical-care pathway for transurethral
      prostatectomy (TURP). PATIENTS AND METHODS: Changes in the length of hospital
      stay and admission charges were identified by comparing a series of 100 patients
      undergoing TURP and treated after implementing a clinical-care pathway with 100
      patients treated by the same physicians before implementation. RESULTS: After
      implementing the care pathway, the mean length of hospital stay and admission
      charges were significantly lower (P < 0.01). The shorter length of stay was
      caused by a significant reduction (P < 0.05) in patient-related
      psychological/social delay after implementation. The number of laboratory tests
      and use of pharmacological agents were also significantly lower (P < 0.001) after
      implementation, with the decreases in these last variables significantly greater
      (P < 0.001) among junior physicians. CONCLUSIONS: The advantages of the TURP
      clinical-care pathway were the shorter hospital stay, arising from reduced
      patient-related psychological or social delay, and reduced admission charges
      consequent on the decreased use of laboratory tests and drugs, particularly for
      patients treated by junior physicians. These results suggest that physicians are
      likely to modify their management methods to improve efficiency when a clinical
      path is implemented.

PMID- 9523659
TI  - A clinical-care pathway for decreasing hospital stay after radical prostatectomy.
AB  - OBJECTIVES: To evaluate the use of a clinical-care pathway that decreased the
      stay in hospital after radical retropubic prostatectomy from 3 to 2 days,
      assessing the costs and quality of care. PATIENTS AND METHODS: Forty-four
      consecutive men who underwent radical retropubic prostatectomy were evaluated
      prospectively. The first 22 men were hospitalized under the standard 3-day
      clinical-care pathway in use at our institution. This pathway was evaluated,
      shortened to construct a 2-day pathway, and a second group of 22 consecutive men
      hospitalized under the new pathway. Both groups were evaluated and compared 6
      weeks post-operatively. RESULTS: The mean (SD) hospital stay was 2.1 (0.3) days
      for men in the 2-day and 2.9 (0.4) days for men in the 3-day pathway (P < 0.001).
      The mean (SD) hospital cost was $8468 (801) in the 2-day and $8806 (630) in the 3
      day pathway (P=0.13). None of the men in the 2-day and one of 22 men in the 3-day
      pathway experienced a major complication (P=0.31). Two of 22 men in the 2-day and
      one of 22 in the 3-day pathway exceeded the expected stay by one day (P=0.55).
      CONCLUSION: The hospital stay after radical retropubic prostatectomy can be
      safely shortened from 3 to 2 days for most men. However, the shorter hospital
      stay does not result in significant cost savings. The shorter stay does not
      appear to compromise quality of care. Proper patient education and careful pre-
      and post-operative supervision are necessary for a successful outcome.

PMID- 9523660
TI  - Transforming growth factor-beta1 serum concentration in patients with prostatic
      cancer and benign prostatic hyperplasia.
AB  - OBJECTIVE: To assess serum levels of transforming growth factor-beta1 (TGF
      beta1), normally markedly elevated in prostate cancer tissue, in patients with
      cancer of the prostate, and to correlate these levels with tumour stage and serum
      prostate specific antigen (PSA) levels. PATIENTS AND METHODS: Serum TFG-beta1 and
      PSA levels were determined in 32 patients with untreated prostate cancer.
      Patients were divided into: group 1, 14 patients with pT1-3pN0M0; group 2, four
      with T1-3pN+M0); and group 3, 14 with T1-4NxM+. Ten patients with histologically
      confirmed benign prostatic hyperplasia (BPH) served as controls. RESULTS: The
      median TGF-beta1 levels were no different between patients with cancer or BPH
      (30.7 ng/mL and 26.9 ng/mL, respectively; P > 0.05). Furthermore, there was no
      increase in TGF-beta1 concentrations with advancing tumour stage (group 1, 34.1
      ng/mL; group 2, 33.0 ng/mL; group 3, 28.3 ng/mL; P > 0.05). There was no
      correlation with PSA levels (group 1, r= -0.42: group 2, r= -0.43; group 3, r= 
      0.23; BPH, r=0.38). CONCLUSION: TGF-beta1 levels did not discriminate between
      patients with BPH and prostate cancer, and there was no increase in TGF-beta1
      levels with advancing tumour stage.

PMID- 9523661
TI  - Expression of E-cadherin in primary prostate cancer: correlation with clinical
      features.
AB  - OBJECTIVE: To correlate the immunohistochemically detected loss of E-cadherin
      expression with patient age, clinical and biological variables, and to
      investigate the prognostic value of these variables for the relapse-free and
      overall survival of patients with different stages of newly diagnosed prostate
      cancer. PATIENTS AND METHODS: Sixty-seven patients (median age 63 years, range 48
      78) undergoing radical prostatectomy for the treatment of primary prostate cancer
      were assessed to determine whether age, tumour stage, histological grading, serum
      levels of prostate specific antigen and prostatic acid phosphatase, regional
      lymph node status and E-cadherin expression were prognostic factors for relapse
      free and overall survival. RESULTS: With a median (range) follow-up of 54 (3-193)
      months, there was no independent prognostic value of decreased E-cadherin
      expression for the long-term or recurrence-free survival of patients, using a
      threshold value of 40% for the relative amount of positively stained tumour
      cells, or for any other threshold value calculated (25%, 60% or 75%). However,
      comparing a follow-up of 16 months in patients with < 40% positivity and 46
      months in patients with > or = 34% positivity, those patients retaining E
      cadherin expression had a significantly longer recurrence-free interval after
      radical prostatectomy (P < 0.01). CONCLUSION: The value of E-cadherin expression
      as an additional independent prognostic variable for patients with primary
      prostate cancer is questionable.

PMID- 9523662
TI  - Prediction of pathological stage and clinical outcome in prostate cancer: an
      improved pre-operative model incorporating biopsy-determined intraductal
      carcinoma.
AB  - OBJECTIVE: To relate the predictive value of serum prostate specific antigen
      (PSA) levels, histological grade and intraductal carcinoma (IDC-P, a possible
      marker of poor prognosis) to pathological stage and subsequent clinical outcome,
      and thus derive an improved predictive model to aid the decision to initiate
      potentially curative therapy in localized prostate cancer. MATERIALS AND METHODS:
      Fifty-nine radical prostatectomy specimens were histologically graded, allocated
      a pathological stage and the tumour volume determined by image analysis. Pre
      operative (needle biopsy) tumour grade, the presence or absence of IDC-P, and
      serum PSA levels were correlated with the pathological stage. This was used to
      define the sequence and values that would be incorporated into a predictive model
      for pathological stage and clinical outcome. RESULTS: There were close
      correlations between cancer volume and tumour grade (P = 0.004) and between
      cancer volume and serum PSA level (P = 0.003). However, in tumours with IDC-P,
      serum PSA level did not correlate with tumour volume of IDC-P (P > 0.9). IDC-P
      was an independent variable that significantly improved the prediction of
      pathological stage and tumour volume, and furthermore, was closely related to (r
      = 0.53, P = 0.001) and accurately predicted treatment failure. CONCLUSION: The
      model which best predicted pathological stage and clinical outcome involved first
      identifying those cancers with IDC-P as having the poorest outcome. Cancers
      without IDC-P were then separated into low- and high-risk groups on the basis of
      serum PSA levels below and above 10 ng/mL, and those in the high-risk group
      further stratified using Gleason grading. Furthermore, the use of a sequential
      consideration of pre-operative variables including IDC-P allowed cases to be
      grouped which, after radical surgery, closely correlated with clinical outcome.

PMID- 9523663
TI  - Free/total serum prostate-specific antigen ratio: how helpful is it in detecting
      prostate cancer?
AB  - OBJECTIVE: To determine whether the use of free/total (f/t) serum prostate
      specific antigen (PSA) ratio would help reduce the number of prostate biopsies
      performed without compromising the detection of prostate cancer. in the setting
      of a transrectal ultrasonography (TRUS) clinic. PATIENTS AND METHODS: The study
      included 93 consecutive patients referred to the clinic for TRUS and biopsy.
      Serum samples were assessed for total PSA and free PSA, and the f/t PSA ratio
      calculated: 70 biopsies were taken. Patients over the age of 70 years with TRUS
      findings consistent with benign prostatic hyperplasia and with PSA levels < 10
      ng/mL were not biopsied. RESULTS: Tumour was detected in 23 patients; receiver
      operating characteristic curves showed no advantage for the f/t PSA ratio when
      compared with total PSA in detecting prostate cancer. If a f/t PSA ratio of <
      0.15 had been used to determine the necessity for biopsy in the group with a
      total PSA of 4-10 ng/mL, then two-thirds of all tumours would have been
      undetected. CONCLUSION: The f/t PSA ratio had no advantage over total PSA in
      improving specificity at a given sensitivity for detecting prostate cancer.
      Therefore, it cannot be recommended as a means of decreasing unnecessary biopsies
      in patients with a raised PSA level and/or an abnormal digital rectal
      examination. This applied particularly to the group of patients with a total PSA
      of 4-10 ng/mL.

PMID- 9523664
TI  - Endogenous neurotransmitters mediating penile erection.

PMID- 9523666
TI  - Vasoactive intestinal polypeptide and phentolamine mesylate administered by
      autoinjector in the treatment of patients with erectile dysfunction resistant to
      other intracavernosal agents.
AB  - OBJECTIVE: To study the effect of vasoactive intestinal polypeptide (VIP) and
      phentolamine mesylate (PM) on patients in whom previous intracavernosal therapy
      had failed. PATIENTS AND METHOD: The study comprised 70 consecutive patients
      attending a clinic for erectile dysfunction, in whom previous therapy with
      intracavernosal prostaglandin-E1 (20 microg and papaverine (30 mg) combined with
      1 mg PM had failed. They were given intracavernosal injections, initially with 25
      microg VIP/1 mg PM (VIP1) and if unsuccessful, 25 microg VIP/2 mg PM (VIP2). Both
      VIP1 and VIP2 were administered using a pre-filled ready-to-use autoinjector
      fitted with a 29 G needle. The patients were diagnosed as having spinal cord
      lesion (eight), diabetes (21), ischaemic heart disease (12), hypertension (six),
      other diagnoses (nine), or idiopathic causes (14). RESULT: Forty-seven (67%) of
      patients achieved erections sufficient for sexual intercourse (33 on VIP1 and 14
      on VIP2), initially under clinical supervision and subsequently during home use.
      Minor side-effects were transient facial flushing in 37 (53%), truncal flushing
      in six (9%), bruising in 14 (20%) and pain from the injection needle in eight
      (11%). No patients reported priapism or other serious adverse events. CONCLUSION:
      The combination of VIP and PM at the dose used was a safe and effective treatment
      in patients in whom other therapies had failed.

PMID- 9523665
TI  - Pharmacological characterization of kinin-induced relaxation of human corpus
      cavernosum.
AB  - OBJECTIVE: To characterize the kinin receptor subtype involved in the relaxation
      of human isolated corpus cavernosum (HCC) induced by bradykinin (BK), Lys
      bradykinin (Lys-BK), Met-Lys-bradykinin (Met-Lys-BK) and des-Arg9-bradykinin, and
      to investigate whether the kinin-induced relaxation of HCC results from the
      stimulation of nonadrenergic, noncholinergic (NANC) neurons supplying the
      cavernosal tissue. MATERIALS AND METHODS: Excised HCC tissues were immediately
      placed in Krebs solution and kept at 4 degrees C until use (never > 24 h after
      removal). HCC was cut in strips of approximately 2 cm, suspended in a cascade
      system and superfused with oxygenated and warmed Krebs solution at 5 mL/min.
      After equilibration for approximately 90 min, noradrenaline (3 micromol/L) was
      infused to induce a submaximal contraction of the HCC strips. The release of
      cyclo-oxygenase products was prevented by infusing indomethacin (6 micromol/L).
      HCC strips were calibrated by injecting a single bolus of the nitrovasodilator
      glyceryl trinitrate (GTN) and the sensitivity of the tissues adjusted
      electronically to be similar. The agonists (kinins, histamine and acetylcholine)
      were injected as a single bolus (up to 100 microL) and the relaxation of HCC
      expressed as a percentage of the submaximal relaxation induced by GTN. RESULTS:
      Bradykinin, Lys-BK and Met-Lys-BK significantly relaxed the HCC tissues; on a
      molar basis, there was no statistical difference among the degrees of relaxation
      induced by these peptides. The B1 kinin receptor agonist des-Arg9-bradykinin had
      no effect on the HCC. The infusion of the B2 kinin receptor antagonist Hoe 140
      (50 nmol/L) virtually abolished the relaxation induced by BK, Lys-BK and Met-Lys
      BK without affecting those induced by acetylcholine and histamine. The infusion
      of the nitric oxide synthase inhibitor N(omega)-nitro-L-arginine methyl ester
      increased the tone of the HCC tissues and significantly reduced (P < 0.01) the
      relaxation induced by BK (74%), Lys-BK (90%), Met-Lys-BK (87%) and acetylcholine
      (89%) without affecting those induced by GTN. The subsequent infusion of L
      arginine (300 micromol/L) partially reversed the increased tone and significantly
      (P < 0.01) restored the relaxation induced by BK, Lys-BK and Met-Lys-BK. The
      results were similar with the novel guanylate cyclase inhibitor 1H-[1,2,4]
      oxadiazolo[4,3,-alquinoxalin-1-one] which reduced by > 95% (P < 0.01) the
      relaxation induced by BK, Lys-BK, Met-Lys-BK, acetylcholine and GTN. The infusion
      of the sodium-channel blocker tetrodotoxin had no significant effect on the BK-,
      GTN- and acetylcholine-induced relaxation of HCC. CONCLUSION: This study clearly
      showed the existence of functional B2 kinin receptors in human erectile tissues
      that when activated lead to the release of NO and hence relaxation of the HCC
      tissues. As tetrodotoxin failed to affect the kinin-induced relaxation of HCC
      strips, it is likely that these peptides release NO from the endothelium of
      sinusoidal capillaries rather than from neuronal sources supplying the cavernosal
      tissue. Although tissue kallikreins and their components have been found in the
      male reproductive system, the physiopathological importance of these findings has
      yet to be elucidated.

PMID- 9523667
TI  - Comparison of intraurethral liposomal and intracavernosal prostaglandin-E1 in the
      management of erectile dysfunction.
AB  - OBJECTIVE: To compare the intraurethral application of liposomal prostaglandin-E1
      (PGE1) with intracavernosal injection of PGE1 in patients with organic or
      psychogenic erectile dysfunction (ED). PATIENTS AND METHODS: Penile tumescence
      and rigidity were classified by palpation in 25 patients (10 with psychogenic and
      15 with organic ED: median age 45 years, range 23-67). All patients were
      undergoing primary treatment for ED, the median (range) duration of which was 2 3
      (2-44) months. After administering PGE1 by each route (1 mg intraurethral and
      0.02 or 0.01 mg intracavernosal), the degree of erection was assessed and duplex
      ultrasonography of the deep penile artery was performed. RESULTS: After the
      intraurethral application of liposomal PGE1, there was mild penile tumescence in
      12 patients with organic ED, the others having no response. In contrast,
      intracavernosal injection produced sufficient rigidity in 13 patients with
      organic ED, while two only had a slight increase in tumescence. In patients with
      psychogenic ED, intraurethral application gave adequate rigidity in six, with
      four having little or no tumescence, and intracavernosal injection induced
      sufficient rigidity for intercourse in all. Duplex ultrasonography of the deep
      penile artery of the penis showed that intraurethral application induced lower
      flow rates than intracavernosal injection. No patient reported pain after
      intraurethral application but two of 25 reported severe pain after
      intracavernosal injection. CONCLUSIONS: The intraurethral application of
      liposomal PGE1 did not produce sufficient rigidity and was not effective in
      patients with organic ED. However, it did produce sufficient rigidity in six of
      10 patients with psychogenic ED and may thus provide a therapeutic alternative in
      selected patients.

PMID- 9523668
TI  - Histological and ultrastructural alterations in an animal model of Peyronie's
      disease.
AB  - OBJECTIVE: To determine the role of transforming growth factor beta (TGF-beta),
      one of the cytokines known to induce tissue fibrosis, in the induction of a
      Peyronie's-like condition, and to produce an animal model for the further study
      of Peyronie's disease. MATERIALS AND METHODS: Twenty-four adult male Sprague
      Dawley rats were divided into two groups: in group 1, different concentrations of
      cytomodulin, a synthetic heptapeptide with TGF-beta-like activity, were injected
      into the tunica of each of 18 rats and six rats group 2 received saline
      injections as a control. The tunical tissues were taken after 3 days, 2 and 6
      weeks and were examined histologically using Hart and trichrome stains. Electron
      microscopy was used to examine the ultrastructural changes in the same tissue
      samples. RESULTS: There were histological and ultrastructural alterations in 15
      of 18 rats in group 1 (cytomodulin-injected), especially in tissue examined after
      6 weeks. The most prominent histological changes were chronic inflammatory
      cellular infiltration, focal and diffuse elastosis, thickening, disorganization
      and clumping of the collagen bundles. The ultrastructural changes were in the
      form of densely packed collagen, fragmented and scarce elastic fibres, separation
      of neuronal fibres by interposing clumps of packed collagen, and perivascular
      collagen deposition as a part of the reorganization of the interstitial matrix.
      CONCLUSION: Cytomodulin can induce a Peyronie's-like condition in the rat penis,
      which may explain the role of TGF-beta in the pathogenesis of Peyronie's disease.
      With further refinement, such rats may be used as an experimental model for
      studies of Peyronie's disease.

PMID- 9523669
TI  - Predicting regional lymph node metastasis in carcinoma of the penis: a comparison
      between fine-needle aspiration cytology, sentinel lymph node biopsy and medial
      inguinal lymph node biopsy.
AB  - OBJECTIVE: To evaluate the accuracy of clinical examination and fine-needle
      aspiration cytology (FNAC) in detecting groin metastases in patients with
      carcinoma of the penis, and to assess the positive and negative predictive value
      (PPV, NPV) of a preliminary sentinel lymph-node biopsy (SNB) and biopsy of the
      most medial of the horizontal group of inguinal lymph nodes (MIN) in selecting
      patients for an ilio-inguinal block dissection. PATIENTS AND METHODS: The study
      comprised 28 patients (56 groins) with Stage I (one), Stage II (11) and Stage III
      (16) carcinoma of the penis. All patients underwent a detailed clinical
      examination followed by FNAC of the palpable inguinal nodes, and were
      subsequently submitted for block dissection. The MIN, the SN and the rest of the
      inguinal and iliac nodes were histologically examined separately for metastases.
      RESULTS: The clinical evaluation had a sensitivity of 74%, a specificity of 61%,
      a PPV of 57% and a NPV of 77%. The corresponding values for FNAC were all 100%,
      and the specificity and PPV for both MIN and SN were 100%. The sensitivity and
      NPV of MIN were higher than for SN, although not significantly so. CONCLUSION:
      Clinical examination alone is inaccurate in selecting patients with carcinoma of
      the penis for block dissection. FNAC is accurate and specific when nodes are
      palpable; in those with impalpable nodes a preliminary MIN biopsy followed by SNB
      if the MIN biopsy is negative will accurately select all patients with metastases
      in the groin nodes. This can be performed by examining frozen sections of the
      lymph nodes; if positive, block dissection can be carried out at the same time.

PMID- 9523670
TI  - Is the timing of post-vasectomy seminal analysis important?
AB  - OBJECTIVE: To review the practice in two hospitals with differing protocols in
      the timing of seminal analysis after vasectomy. PATIENTS AND METHODS: The results
      from 245 vasectomies carried out at Hospital A, where semen was assessed 3 months
      after vasectomy, were reviewed and compared with those from 100 consecutive
      vasectomies at Hospital B, where semen was assessed 6 months after vasectomy. The
      results of seminal analysis at Hospital A were also audited after changing to the
      6-month protocol. The patients' preferences for the timing of seminal analysis
      were also obtained. RESULTS: Of the 245 patients at Hospital A, 58 (24%) failed
      to provide samples, leaving 187 (76%) for evaluation; 528 samples were examined
      (mean 2.8 per patient, range 1-13). The first sample was positive in 36 (19.3%)
      and the second positive in 10 (5.3%), the first being negative. Four (2%)
      patients had persistent spermatozoa at 6 months, one subsequently undergoing
      exploration. Thirty-one (17%) patients provided further samples despite providing
      two consecutive clear ones. At Hospital B, 24 (24%) patients failed to provide
      samples; 10 (13%) patients had persistent spermatozoa at 6 months and live
      spermatozoa were detected in one patient's samples. All eventually produced clear
      samples, with none requiring exploration. After changing the protocol, 87
      vasectomies were performed, with 18 (21%) patients failing to provide samples;
      seven (10%) of the samples collected showed occasional nonmotile spermatozoa at 6
      months in either the first, second or both samples, with all samples clear by 8
      months after vasectomy. CONCLUSIONS: The complete disappearance of spermatozoa
      after vasectomy takes longer than is generally believed and we therefore suggest
      that given adequate counselling, seminal analysis 6 months after vasectomy is
      cost-effective and in the patient's interest.

PMID- 9523671
TI  - Urodynamic patterns in infants with normal lower urinary tracts or primary vesico
      ureteric reflux.
AB  - OBJECTIVE: To compare bladder function in infants with primary vesico-ureteric
      reflux (VUR) and those with normal lower urinary tracts. PATIENTS AND METHODS:
      The study comprised 42 patients (36 males) with VUR (grades III to V) and 21 (16
      males) without VUR (mean age in both groups, 6 months). Intravesical catheters
      were placed suprapubically under general anaesthesia and, after at least 24 h,
      natural-tilling urodynamics were monitored for three or more filling and voiding
      cycles. RESULTS: Various urodynamics patterns were defined: for infants without
      VUR these were either normal or normal-immature (discoordinated micturition) and
      none showed features indicating abnormal bladder function. By comparison, 24 of
      42 infants with VUR showed abnormal urodynamic patterns (57%, 95% confidence
      interval 41% to 72%, P < 0.001). Seven (17%) were defined as unstable with small
      voided volumes, five (12%) had inadequate voiding dynamics, 10 (24%) showed a
      markedly dyssynergic pattern and two (5%) had obstructive patterns. The unstable,
      inadequate and obstructive patterns occurred only in boys. Detrusor activity
      during the filling phase occurred in 14 infants (13 boys) with VUR and in only
      one without VUR, when it was trivial. Post-void residual volumes of > 30%
      capacity were seen only in the VUR group (in 24 patients). There were 18 infants
      with VUR that showed the normal or immature urodynamics patterns, but for the 14
      males the voiding pressures were higher than for those without VUR (mean maximum
      detrusor pressure, 161 and 117 cmH2O, respectively: P < 0.02). CONCLUSIONS: There
      is an association between abnormal urodynamic variables and a diagnosis of
      primary VUR in young infants (notably males) that may have important implications
      for concepts about the genesis and persistence of VUR.

PMID- 9523672
TI  - Cystometry in infants and children with no apparent voiding symptoms.
AB  - OBJECTIVE: To evaluate bladder function in infants and children with no apparent
      voiding symptoms. SUBJECTS AND METHODS: The study included 83 infants and
      children (51 boys and 32 girls, aged 3 days to 12 years) with no neurological and
      lower urinary tract pathology but who had undergone or were about to undergo
      surgery for upper urinary tract or other pathology. They were evaluated using
      slow-filling cystometry, with simultaneous electromyography recorded using
      surface electrodes on the perineum. The voiding variables were compared among
      groups categorized by age, sex and body weight. RESULTS: In boys and girls,
      respectively, the mean (SD) post-void residual urine volume (PVR) was 6.3 (3.9)
      and 5.4 (4.8) mL, the maximum detrusor pressure during voiding was 66.1 (13.1)
      and 56.6 (14.7) cmH2O and the maximum voiding pressure was 73.9 (16.6) and 62.7
      (16.2) cmH2O. There was no significant difference in these variables between the
      sexes or between infants and children (P > 0.05). Detrusor instability (DI) was
      apparent in nine of 83 (10.8%) infants and children and occurred in the late
      filling phase. Bladder capacity increased with age and body weight (from 30 mL in
      neonates to 350 mL in 12-year-old children), and mean (SD) bladder compliance
      increased with age, from 3.6 (0.5) mL/cmH2O in infants to 13.3 (3.0) mL/cmH2O in
      older children, at a filling rate of 5-7 mL/min. CONCLUSIONS: In these infants
      and children with no apparent voiding symptoms, most bladders were stable, DI
      could occur in the late filling phase of cystometry, voiding was nearly complete,
      the PVR being usually < 10 mL, and bladder capacity increased with age and body
      weight.

PMID- 9523673
TI  - A single-system ectopic ureter draining an ectopic dysplastic kidney: delayed
      diagnosis in the young female with continuous urinary incontinence.
AB  - OBJECTIVE: To document the array of diagnostic modalities, the variety of errant
      diagnoses and treatments. and the time from initial presentation to ultimate
      diagnosis in girls with an ectopic single-system ureter draining an ectopic
      hypoplastic and/or dysplastic kidney. PATIENTS AND METHODS: Between 1990 and
      1997, seven females were identified who had an ectopic hypoplastic and/or
      dysplastic kidney with an ectopically draining ureter, and who were treated at
      our institutions, either initially or upon referral. The nature and number of all
      diagnostic evaluations, previous diagnoses and treatments, and the time from
      presentation to definitive diagnosis were recorded. RESULTS: All seven females
      had a classical history of successful toilet training, a normal voiding pattern
      and continuous urinary incontinence. Typically, a solitary kidney was noted on
      the initial diagnostic evaluation by ultrasonography and/or intravenous
      urography. The mean (range) age at initial presentation was 3.2 (2-6) years.
      Additionally, voiding cysto-urethrography, urodynamics, radionuclide
      scintigraphy, computed tomography, magnetic resonance imaging and endoscopy were
      performed. The age at definitive diagnosis was 3-16.5 years and the mean (range)
      time from initial presentation to diagnosis was 5.7 (1-10) years.
      Nephroureterectomy was curative and all kidneys were dysplastic. CONCLUSION:
      Continuous urinary incontinence in females with a normal voiding pattern should
      prompt an evaluation for ureteric ectopia. When the initial evaluation yields the
      diagnosis of a solitary kidney, clinicians should be aware of the possibility of
      a hypoplastic and/or dysplastic, often ectopic, contralateral kidney with an
      ectopically draining ureter. Identification of this entity should allow curative
      surgical treatment.

PMID- 9523674
TI  - The penile disassembly technique in hypospadias repair.
AB  - OBJECTIVE: To report experience and results with penile disassembly in
      hypospadias repair. PATIENTS AND METHODS: From November 1995 to May 1997 penile
      disassembly was used in 92 patients aged from 9 months to 32 years. The
      indications for operation were hypospadias with severe penile curvature
      (especially with curvature in the distal third of the corpora cavernosa), chordee
      without hypospadias, and small penis with hypospadias. The technique involves
      separating the penis into its component parts, i.e. the glans cap with
      neurovascular bundle dorsally, together with the undivided or divided urethra and
      urethral plate ventrally, and the corpora cavernosa. The manoeuvre allows any
      curvature to be corrected, especially when in the distal third of the corporal
      bodies, glans tilt to be rectified, and the penis to be enlarged, particularly
      elongated, which is a significant gain in small penises with hypospadias.
      RESULTS: The patients were followed for 3-20 months (mean 14); the penis was
      straightened in all cases, with no recurrence of curvature. In 37 patients (40%)
      penile disassembly combined with extensive urethral mobilization resolved the
      hypospadiac meatus with no need to form a neourethra; the penis was larger after
      surgery. Complications were related to urethroplasty and included four urethral
      stenoses, two fistulae and three diverticula. There was no injury to the
      neurovascular bundle and urethra; sensitivity and erection were preserved in all
      patients. CONCLUSION: The penile disassembly technique is most effective for
      hypospadias with severe curvature, especially for glans tilt and curvature
      located distally. Penile augmentation is possible using this technique.

PMID- 9523675
TI  - A needle-pusher for urethral suture placement in urethrovesical anastomosis.

PMID- 9523676
TI  - Simple, safe and inexpensive retrieval of JJ stents with a flexible cystoscope.

PMID- 9523677
TI  - Massive bladder hernia: ultrasonographic imaging in two cases.

PMID- 9523678
TI  - Inactivation of the retinoblastoma susceptibility gene in metachronous eye and
      bladder tumours.

PMID- 9523679
TI  - Acid-fast bacilli persisting in the genitourinary tract 3 years after
      intravesical bacille Calmette-Guerin therapy for bladder carcinoma.

PMID- 9523680
TI  - Spontaneous passage of shotgun pellets during voiding.

PMID- 9523681
TI  - Colovesical fistula following ingestion of a foreign body.

PMID- 9523682
TI  - Transhepatic venous collaterals arising from inferior vena caval extension of
      renal cell carcinoma.

PMID- 9523683
TI  - Failure of seminal emission in retroperitoneal fibrosis.

PMID- 9523684
TI  - Bilateral crossed testicular ectopia with unilateral absence of the vas deferens:
      a possible case and hypothetical mechanism.

PMID- 9523685
TI  - Prostatic cancer 30 years after bilateral orchidectomy.

PMID- 9523686
TI  - Penile necrosis after coronary artery bypass grafting.

PMID- 9523687
TI  - The urokinase-type-plasminogen-activator receptor (CD87) is a pleiotropic
      molecule.
AB  - Since its discovery over a decade ago, evidence has accumulated implicating the
      cell-surface urokinase receptor (u-PAR), in numerous biological processes. Most
      notable has been the identification of a critical role for u-PAR in the
      regulation of cell-surface plasminogen activation in physiological and
      pathological conditions. Recent evidence suggests that u-PAR, a
      glycosylphosphatidylinositol-linked receptor, lacking transmembrane and
      cytoplasmic domains, is also involved in processes not related to plasminogen
      activation, including cellular adhesion and the transmission of extracellular
      signals across the plasma membrane. Involvement of activated u-PAR in these
      events identifies previously unsuspected roles for this molecule and defines a
      new field of research in u-PAR biology. We discuss the molecular biology of u-PAR
      together with the underlying mechanisms responsible for the novel functional
      roles recently ascribed to this pleiotropic molecule.

PMID- 9523688
TI  - Effects of adrenal steroid hormones on mitochondrial maturation during the late
      fetal period.
AB  - In the present work, we described the perinatal changes in mitochondrial
      maturation that contribute to metabolic development in the rat kidney. We focused
      on cytochrome-c oxidase activity and gene expression from the last three days of
      gestation to one day after birth. The role of adrenal steroids in the development
      of cytochrome-c oxidase expression and of mitochondrial DNA content was also
      investigated by studying the effects of fetal adrenalectomy. During the perinatal
      period, the developmental pattern of the cytochrome-c oxidase enzymatic complex
      exhibited parallel increases in transcript levels, protein content and enzyme
      activity, suggesting a transcriptional regulation of this enzyme. Adrenalectomy
      led to a decrease in fetal kidney cytochrome-c oxidase messengers and mtDNA
      content while administration of dexamethasone restored normal levels. In
      contrast, mtDNA content was unchanged in liver and heart after adrenalectomy
      whereas levels of cytochrome-c oxidase transcripts were controlled by adrenal
      steroids in liver but not in heart. These results indicate that adrenal steroid
      hormones contribute to the regulation of perinatal maturation of mitochondria in
      rat kidney and that these hormones are involved in the fetal mitochondrial
      biogenesis in a tissue-specific manner.

PMID- 9523689
TI  - Molecular and immunological characterization of group V allergen isoforms from
      velvet grass pollen (Holcus lanatus).
AB  - Group V grass pollen allergens belong to the major grass pollen allergens causing
      reactions of type I allergy. cDNAs coding for two isoforms of the group V
      allergen of velvet grass pollen (Holcus lanatus), a widespread grass species,
      were isolated from a cDNA library by hybridization with a 5'-terminal reverse
      transcribed PCR-derived cDNA probe. Amino acid sequences of the two isoforms,
      designated rHol l 5.01 and rHol l 5.02, revealed high similarity between them
      (78% identity) and to group V allergens and their isoforms found in other grass
      species. Recombinant Hol l 5 isoforms were expressed in Escherichia coli and
      purified as fusion proteins. To compare their immunological reactivities with
      group-V-specific monoclonal antibodies and patients' IgE, immunoblotting, ELISA
      and histamine release assay were performed. Interestingly, monoclonal antibody
      Bo9, specific for group Vb isoforms of timothy grass, bound only to isoform rHol
      l 5.01, not to rHol l 5.02. On the other side, IgE reactivities of patients' sera
      revealed no differences between the two isoforms when investigated by
      immunoblotting and only slight differences when investigated by ELISA. In
      histamine release assay both isoforms released comparable amounts of histamine
      from basophils of four individual patients. Thus, the two group V isoforms of
      velvet grass pollen exhibit differential binding when tested with monoclonal
      antibodies, i.e. different structure of single epitopes, but negligible
      differences concerning overall IgE-binding capacity and histamine-releasing
      capacity.

PMID- 9523691
TI  - Semenogelin I and semenogelin II, the major gel-forming proteins in human semen,
      are substrates for transglutaminase.
AB  - The major seminal vesicle secreted proteins in human semen, semenogelin I and
      semenogelin II, interact non-covalently and via disulphide bridges to instantly
      form a coagulum upon ejaculation. The coagulum is liquefied after a few minutes
      due to the action of a prostatic serine protease, prostate-specific antigen
      (PSA). In contrast to rat semen, which forms an insoluble plug within minutes of
      expulsion, no transglutaminase-mediated cross-linking has been demonstrated in
      ejaculated human semen. However, we here show that semenogelin I and semenogelin
      II, both in seminal vesicle fluid and purified from semen, are substrates for
      factor XIIIa, the fibrin cross-linking transglutaminase. The cross-linking of the
      semenogelins, which was conformation-dependent, and the incorporation of a
      fluorescence-labelled amine, were visualised by SDS/PAGE and Western blot.
      Purified semenogelin I and semenogelin II could be cross-linked separately into
      complexes. Moreover, digestion of semenogelin with PSA produced fragments, some
      of which were cross-linked into complexes by factor XIIIa. We also found that PSA
      was unable to release any semenogelin fragments during exposure of the high
      molecular-mass complexes of cross-linked semenogelin to active PSA.

PMID- 9523690
TI  - Human cancer cell lines growth inhibition by GTn oligodeoxyribonucleotides
      recognizing single-stranded DNA-binding proteins.
AB  - Oligonucleotides can specifically target not only nucleic acids but also
      proteins. Some proteins recognizing oligonucleotides in a sequence-specific
      manner have been related to cancer transformation and progression. We have found
      that oligonucleotides composed by repeated and/or variable intervals of GTn with
      1 < or = n < or = 7, are able to exert a specific and dose-dependent growth
      inhibition on human CCRF-CEM, CEM-VLB300, U937, Jurkat, H9 and HeLa tumor cell
      lines. In contrast, G-->C, G-->A, T-->C and T-->A base substituted control
      oligonucleotides do not significantly alter cellular growth. In all cell lines, a
      nuclear protein (molecular mass = 45+/-7 kDa), which specifically recognizes GTn,
      was identified. Our hypothesis is that the formation of the GTn-protein complex
      in human cancer cell lines may be involved in the growth inhibition effect. In
      fact, we found that the reduction or lack of cytotoxic effects by GTn in phorbol
      12-myristate 13-acetate-treated CCRF-CEM cells and in normal human lymphocytes is
      paralleled by the simultaneous reduction or lack of GTn-protein complex.
      Oligonucleotides specifically 'quenching' intracellular protein activities by
      forming oligonucleotide-protein complexes may be of potential interest in the
      treatment of human tumors.

PMID- 9523692
TI  - The accessible surface of the nicotinic acetylcholine receptor. Identification by
      chemical modification and cross-linking with 14C-dimethyl suberimidate.
AB  - To obtain structural information on the nicotinic acetylcholine receptor from
      Torpedo electric tissue we modified and cross-linked lysine residues with the
      agonistic bifunctional reagent [14C]dimethyl suberimidate. This reagent labels
      exposed lysine residues, especially those located near the ligand-binding site,
      and cross-links lysine residues located not more than 11 A, the length of the
      cross-linker, apart. Using this method, we identified a cross-link located
      between betaLys177 and betaLys191 showing that the 13 amino acids in between form
      a loop with these two residues located at the surface. Cross-linking also
      occurred between the vicinal lysine residues alphaLys76 and alphaLys77,
      indicating that these neighbouring lysine residues are not involved in a beta
      sheet structure. A total of 21 out of 97 lysine residues present in the receptor
      were modified by [14C]dimethyl suberimidate. Thus these residues are located on
      the accessible extramembrane surface. The two lysine residues alphaLys76 and
      alphaLys179 were predominantly labelled. Because of the agonistic property of
      [14C]dimethyl suberimidate [Watty, A., Methfessel, C. & Hucho, F. (1997) Proc.
      Natl Acad. Sci. USA 94, 8202-8209] this might be due to their close proximity to
      the ligand binding site.

PMID- 9523694
TI  - Purification, properties and in situ localization of the amphibolic enzymes D
      ribulose 5-phosphate 3-epimerase and transketolase from spinach chloroplasts.
AB  - The amphibolic enzymes D-ribulose 5-phosphate 3-epimerase and transketolase have
      been purified from stroma extracts of spinach chloroplasts using ammonium sulfate
      fractionation and FPLC. For the native enzymes, a molecular mass of 180 kDa for
      epimerase and 160 kDa for transketolase was found and the molecular masses of the
      subunits was determined to be 23 kDa for epimerase and 74 kDa for transketolase.
      Protein sequencing of the purified chloroplast enzymes revealed the NH2-terminal
      amino acid sequences of mature epimerase (NH2-TSRVDKFSKSDIIVSP) and transketolase
      (NH2-AAVEALESTDTDQLVEG). The enzymic properties of both enzymes such as Km values
      or pH optima, were found to be very similar to those for epimerases and
      transketolases from other sources, including yeast and animal cells. In contrast
      to the light-activated enzymes of the Calvin cycle, the activity of these
      amphibolic enzymes was not redox-dependent. Immunogold electron microscopy on
      spinach leaf thin sections revealed that about 90% of the total epimerase and
      transketolase, and 96% of the total chloroplast H+-ATP synthase portion CF1 are
      associated with thylakoid membranes in situ. Ribulose-1,5-bisphosphate
      carboxylase/oxygenase, in contrast, was evenly distributed throughout
      chloroplasts. These and other results indicate that minor chloroplast enzymes are
      arranged in a thin layer on thylakoid membrane surfaces in vivo.

PMID- 9523693
TI  - Enzymic confirmation of reactions involved in routes to astaxanthin formation,
      elucidated using a direct substrate in vitro assay.
AB  - An in vitro assay procedure for the carotenoid (beta-ionone ring) 3,3'
      hydroxylase and 4,4'-oxygenase has been developed that enables efficient
      conversion of non-radiolabeled carotenoid substrates added directly into aqueous
      solution. The following enzymic conversions were demonstrated and apparent
      kinetic constants (Vmax, Km, and specificity constants) obtained: (a) 3,3'
      hydroxylase (from Agrobacterium aurantiacum and Alcaligenes sp. strain PC-1)
      converted phoenicoxanthin (adonirubin) to astaxanthin, 3-hydroxyechinenone to 4
      ketozeaxanthin (adonixanthin), 3'-hydroxyechinenone to 4-ketozeaxanthin, as well
      as echinenone to 4-ketozeaxanthin via 3- and 3'-hydroxyechinenone; (b) 4,4'
      Oxygenase (from A. aurantiacum, Alcaligenes sp. strain PC-1 and Haematococcus
      pluvialis) converted 4-ketozeaxanthin to astaxanthin, 3-hydroxyechinenone to
      phoenicoxanthin, 3'-hydroxyechinenone to phoenicoxanthin, and echinenone to
      canthaxanthin. Determination of substrate specifities allowed assessment of
      biosynthetic routes to astaxanthin formation and demonstrated that pathways via
      mono-hydroxylated and ketolated products are enzymically feasible.

PMID- 9523695
TI  - Isolation and characterisation of cAMP-dependent protein kinase from Candida
      albicans. Purification of the regulatory and catalytic subunits.
AB  - cAMP-dependent protein kinase (PKA) from Candida albicans yeast cells was
      isolated and characterised. Structural parameters of the holoenzyme and those of
      its subunits suggested that C. albicans PKA is a tetramer of 287 kDa composed of
      two regulatory (R) subunits of 64 kDa and two catalytic (C) subunits of unusually
      large molecular mass of 78 kDa. The apparent Km for ATP and Kemptide were 30
      microM and 60 microM respectively. The [A]0.5 for cAMP activation was 150 nM with
      a Hill coefficient of 1.6. The holoenzyme undergoes autophosphorylation on the R
      subunit, a characteristic of the type-II R subunits. Photoaffinity labeling with
      8-azido-[32P]cAMP of crude extracts from yeast and mycelial cells strongly
      suggests that only one type of R subunit is present in the fungus. The R subunit
      was purified to apparent homogeneity as a protein of 64 kDa. A highly specific
      polyclonal antiserum raised against the purified protein immunoprecipitated a 64
      kDa protein from crude extracts, indicating that the purified R subunit very
      probably represents the native form of the protein. The 78-kDa form of the C
      subunit was detected in crude extracts and in Mono Q Sepharose column fractions
      with heterologous anti-C Ig. It could be isolated by cAMP treatment of the
      holoenzyme immunoprecipitated from crude extracts with anti-R serum, but this
      form could not be purified further. Instead, a 60-kDa protein with the main
      characteristics of C subunit was purified to near homogeneity from soluble
      extracts of yeast cells. Evidence is presented that this protein very probably
      derives from the 78-kDa form by proteolytic degradation.

PMID- 9523697
TI  - Secondary structure of the intact H+,K+-ATPase and of its membrane-embedded
      region. An attenuated total reflection infrared spectroscopy, circular dichroism
      and Raman spectroscopy study.
AB  - Models of P-type ATPase predict that membrane-embedded fragments represent about
      20% of the protein and adopt an all-alpha-helical structure. While this
      prediction was confirmed for the Ca2-ATPase [Corbalan-Garcia, S., Teruel, J.,
      Villalain, J. & Gomez-Fernandez, J. (1994) Biochemistry 33, 8247-8254], it is at
      odds with recent experimental evidence gathered on the Neurospora crassa plasma
      membrane H+-ATPase [Vigneron, L., Ruysschaert, J.-M. & Goormaghtigh, E. (1995) J.
      Biol. Chem. 270, 17685-17696] and on the gastric H+,K+-ATPase [Raussens, V.,
      Ruysschaert, J.-M. & Goormaghtigh, E. (1997) J. Biol. Chem. 276, 262-270].
      Extensive proteinase K proteolysis of open gastric tubulovesicles was performed
      here to generate the membrane-protected fragments of the H+,K+-ATPase. Secondary
      structure of the intact and of the membrane-protected segments was compared for
      oriented membrane films by attenuated total-reflection Fourier-transform infrared
      spectroscopy and by circular dichroism and for vesicles suspension by circular
      dichroism and Raman spectroscopy. All the spectroscopic data indicate that the
      protease-resistant membrane-bound residue of the H+,K+-ATPase contains
      significant amount of beta-sheet structure, both on films and in membrane
      suspensions. Polarized attenuated total-reflection infrared spectroscopy
      indicates that only the alpha-helical content of protease-resistant membrane
      bound residue of the H+,K+-ATPase is oriented (parallel) with respect to the
      membrane normal. Raman spectroscopy reveals that Phe residues are preferentially
      removed by protease activity. Evaluation of the amount of removed Phe and Tyr
      residues places constraints on the model of membrane insertion of the H+,K+
      ATPase.

PMID- 9523696
TI  - Structural analysis of oligosaccharide-alditols released by reductive beta
      elimination from the jelly coats of the anuran Bufo arenarum.
AB  - Amphibian egg jelly coats are formed by components secreted along the oviduct.
      These secretion products overlay the oocytes as they are transported toward the
      cloaca. Mucin type glycoproteins are the major constituents of the egg jelly
      coats. In this study, the O-linked carbohydrate chains of the jelly coat
      surrounding the eggs of Bufo arenarum were released by alkaline borohydride
      treatment. Fractionation of the mixture of O-linked oligosaccharide-alditols was
      achieved by a combination of chromatographic techniques comprising gel-permeation
      chromatography, ion-exchange chromatography and high-performance liquid
      chromatography using an amino-bonded silica column, afforded 11 fractions. The
      primary structures of these O-glycans were determined by one-dimensional and two
      dimensional 1H-NMR spectroscopy in conjunction with matrix-assisted laser
      desorption-ionization--time-of-flight mass spectrometry. 11 oligosaccharide
      structures, possessing a core consisting of Galbeta1-->3GalNAc-ol with or without
      branching through a GlcNAc residue linked beta1-->6 to the GalNAc residue (core
      type 2 or core type 1, respectively) are described. These oligosaccharide
      alditols with these types of cores have been identified previously in mammalian
      mucins or in oviducal amphibian jellies. These glycans contain blood group
      determinants such as H, A or Cad antigens.

PMID- 9523698
TI  - Localization of the 23-kDa subunit of the oxygen-evolving complex of photosystem
      II by electron microscopy.
AB  - A dimeric photosystem II light-harvesting II super complex (PSII-LHCII SC),
      isolated by sucrose density gradient centrifugation, was previously structurally
      characterized [Boekema, E. J., Hankamer, B., Bald, D., Kruip, J., Nield, J.,
      Boonstra, A. F., Barber, J. & Rogner, M. (1995) Proc. Natl Acad. Sci. USA 92, 175
      179]. This PSII-LHCII SC bound the 33-kDa subunit of the oxygen-evolving complex
      (OEC), but lacked the 23-kDa and 17-kDa subunits of the OEC. Here the isolation
      procedure was modified by adding 1 M glycine betaine (1-carboxy-N,N,N
      trimethylmethanaminium hydroxide inner salt) to the sucrose gradient mixture.
      This procedure yielded PSII-LHCII SC that contained both the 33-kDa and the 23
      kDa subunits and had twice the oxygen-evolving capacity of the super complexes
      lacking the 23-kDa polypeptide. Addition of CaCl2 to PSII-LHCII SC with the 23
      kDa subunit attached did not increase the oxygen-evolution rate. This suggests
      that the 23-kDa subunit is bound in a functional manner and is present in
      significant amounts. Over 5000 particle projections extracted from electron
      microscope images of negatively stained PSII-LHCII SC, isolated in the presence
      and absence of glycine betaine, were analyzed using single-particle image
      averaging techniques. Both the 23-kDa and 33-kDa subunits could be visualized in
      top-view and side-view projections. In the side view the 23-kDa subunit is seen
      to protrude 0.5-1 nm further than the 33-kDa subunit, giving the PSII particle a
      maximal height of 9.5 nm. Measured from the centres of the masses, the two 33-kDa
      subunits associated with the dimeric PSII-LHCII SC are separated by 6.3 nm. The
      corresponding distance between the two 23-kDa subunits is 8.8 nm.

PMID- 9523699
TI  - Fluorescence resonance energy transfer mapping of subunit delta in spinach
      chloroplast F1 ATPase.
AB  - Despite the considerable progress in the field of F0F1-ATPases caused by solving
      the 2.8-A structure of mitochondrial F1 ATPase [Abrahams, J. P., Leslie, A. G.
      W., Lutter, R. & Walker, J. E. (1994) Nature 370, 621-628], little is known about
      the position and function of the enzyme's small subunits which were not resolved
      in the X-ray analysis. We have previously genetically engineered Cys residues
      into the delta subunit of chloroplast F1 and used these mutant subunits in cross
      linking studies [Lill, H., Hensel, F., Junge, W. & Engelbrecht, S. (1996) J.
      Biol. Chem. 271, 32737-32742]. In this work, various fluorophores have been
      introduced into the mutant delta subunits and used in fluorescence-resonance
      energy-transfer measurements. The resulting distances were fitted into the
      framework of existing data. Subunit delta was found to be located between two
      alpha/beta couples, stretching from the level of the nucleotide binding sites up
      to a position close to the N-termini of subunits alpha and beta. These results
      corroborate and further refine the previously found location of spinach CF1 delta
      at the periphery and membrane-distal part of CF1, where it may constitute a part
      of a stator in the rotatory machinery of F0F1.

PMID- 9523700
TI  - Identification of a specific effector of the small GTP-binding protein Rap2.
AB  - Rap2 is a small GTP-binding protein that belongs to the Ras superfamily and whose
      function is still unknown. To elucidate Rap2 function, we searched for potential
      effectors by screening a mouse brain cDNA library in a yeast two-hybrid system
      using as a bait a Rap2A protein bearing a mutation of Gly to Val at position 12.
      This strategy lead to the identification of a protein that interacts specifically
      with Rap2A complexed with GTP, and requires an intact effector domain of Rap2A
      for interaction; we designated this protein Rap2-interacting protein 8 (RPIP8).
      Biochemical data obtained from in vitro studies with purified proteins confirmed
      the genetic results. Mouse RPIP8 consists of 446 amino acids, bears a coiled-coil
      domain between residues 265 and 313, and is expressed principally in brain. Its
      human counterpart, of 400 amino acids, exhibits 93.7% identity in their common
      region. A search for similar sequences in expressed-sequence-tags databanks
      revealed the presence in human and rodents of mRNAs encoding the 400-residue and
      446-residue forms of RPIP8. Furthermore a doublet of 45-50 kDa, corresponding to
      the 400-residue and 446-residue forms of the protein, was detected by western
      blotting of mouse brain extracts and lysates from pheochromocytoma PC12 cells and
      the pancreatic beta-cell lines HIT-T15 and RIN-m5F. Using transient transfections
      of HIT-T15 cells it was possible to demonstrate that [Val12]Rap2 and wild-type
      Rap2 could be immunoprecipitated with RPIP8. These data therefore argue for RPIP8
      being a specific effector of the Rap2 protein in cells exhibiting neuronal
      properties.

PMID- 9523701
TI  - Primary cause of mortality in the armyworm larvae simultaneously parasitized by
      parasitic wasp and infected with bacteria.
AB  - Parasitoid wasps never kill their hosts before the wasp larvae emerge from the
      host. However, almost 100% of the host armyworm larvae Pseudaletia separata die
      within 2-3 days by parasitization with the wasp Cotesia kariyai or by injection
      of polydnavirus, the wasp symbiont virus, when they are simultaneously infected
      by the pathogenic bacterium Serratia marcescens. The present study was conducted
      to elucidate the crucial factor causing this larval mortality. An insecticidal
      protein has been shown to exist in the hemolymph of dying host larvae; it has
      been purified by procedures consisting of reverse-phase column extraction, gel
      filtration and ion-exchange column chromatography. The purified protein showed a
      strong insecticidal effect with a median lethal dosage (LD50) of 13 pmol/larva
      and was estimated to have a molecular mass of 57 kDa. The amino acid sequence of
      the insecticidal protein was partially characterized and used for isolation and
      sequencing of the genomic DNA. The deduced amino acid sequence for this protein
      revealed striking similarity with the metalloprotease of S. marcescens
      enterobacter.

PMID- 9523702
TI  - Functional analysis of the guanylate kinase-like domain in the synapse-associated
      protein SAP97.
AB  - SAP97 is a membrane cytoskeletal protein localized at the presynaptic nerve
      terminals of type 1 asymmetric synapses. It has been implicated in the assembly
      of synapses and in particular in the localization and clustering of ion channels.
      The C-terminal GK domain of SAP97 shares a high degree of sequence similarity
      with low-molecular-mass guanylate kinases. These enzymes are involved in the
      guanine nucleotide metabolic cycle and in the maintenance of GTP/GDP pools
      required for example in Ras-mediated cell signaling. It has therefore been
      hypothesized that SAP97 plays an essential role in cellular signaling by
      regulating the guanine nucleotide pools at synaptic junctions. Here, we test this
      hypothesis by assessing whether the GK domain in SAP97 encodes an authentic
      guanylate kinase. We show that the GK domain in and of itself does not encode an
      active guanylate kinase, that it cannot be activated by its binding partner GKAP
      and that flanking regions are not acting as inhibitory regulators for enzymatic
      activity. Thus, it would appear that the GK domain of SAP97 is not involved in
      the metabolism of guanine nucleotides required for signaling events.

PMID- 9523703
TI  - Characterization of wheat thioredoxin h cDNA and production of an active Triticum
      aestivum protein in Escherichia coli.
AB  - Two cDNA clones, pTaM13.38 and pTd14.13.2, encoding a Triticum aestivum and a
      Triticum durum thioredoxin h, respectively, were isolated from mid-maturation
      seed cDNA libraries. The T aestivum thioredoxin h has a molecular mass of 13.5
      kDa and that from T durum has a molecular mass of 13.8 kDa. These two wheat
      thioredoxin h are 98.5% similar and contain the canonical WCGPC active site and
      the important structural and functional amino acids that are conserved in
      thioredoxin sequences. The recombinant T. aestivum thioredoxin h (TrxTa)
      overproduced in BL21(DE3)pLysS was purified to homogeneity by a three-step
      procedure including heat treatment, anion-exchange chromatography and gel
      filtration. TrxTa showed a lower stability to high temperature than Escherichia
      coli thioredoxin or plant thioredoxin m. The molecular mass of TrxTa, determined
      by mass spectrometry, is 13,391 Da and corresponds to a protein lacking the first
      methionine residue, as confirmed by its N-terminal end sequence AASAAT. Using the
      5,5'-dithiobis(2-nitrobenzoic acid)-reduction assay and monobromobimane
      revelation we showed that TrxTa is specifically reduced by wheat NADP:thioredoxin
      reductase (NTR), and not by E. coli NTR. TrxTa is able to reduce identified
      target proteins i.e. wheat seed alpha-amylase inhibitors (chloroform/methanol
      soluble proteins). The presence of a putative transmembrane domain at the N
      terminal end of the two wheat thioredoxins raises the question of whether these
      proteins are membrane anchored.

PMID- 9523704
TI  - 3,5-Diiodothyronine binds to subunit Va of cytochrome-c oxidase and abolishes the
      allosteric inhibition of respiration by ATP.
AB  - The short-term effects of thyroid hormones, which do not occur via gene
      expression, were postulated to be based on interaction of diiodothyronines with
      mitochondria. We demonstrate specific binding of labelled 3,5-diiodothyronine to
      subunit Va of cytochrome-c oxidase from bovine heart. 3,5-Diiodothyronine, and to
      a small extent triiodothyronine, but not thyroxine and thyronine, abolish the
      allosteric inhibition of ascorbate respiration of reconstituted cytochrome c
      oxidase by ATP [Arnold, S. & Kadenbach, B. (1997) Eur. J. Biochem. 249, 350-354].
      This abolition of ATP-inhibition by 3,5-diiodothyronine is completely prevented
      by a monoclonal antibody to subunit Va. The results explain at the molecular
      level the short-term action of thyroid hormones on basal metabolic rate.

PMID- 9523705
TI  - Alpha-glucan binding of potato-tuber starch-branching enzyme I as determined by
      tryptophan fluorescence quenching, affinity electrophoresis and steady-state
      kinetics.
AB  - The affinity of potato tuber starch-branching enzyme-I (PSBE-I) for various
      linear malto-oligosaccharides, cyclodextrins, (CDs) and macromolecular alpha
      glucans was investigated by alpha-glucan induced fluorescence quenching of
      intrinsic PSBE-I tryptophan residues and by affinity electrophoresis. alpha
      Glucan binding was characterised by distinct shifts towards shorter wavelengths
      of the PSBE-I fluorescence emission spectrum and by concomitant reductions in
      fluorescence intensity. The magnitudes of both the maximum shift in emission
      spectrum and reduction in fluorescence intensity were dependent on the alpha
      glucan ligands used. Maximum Kd for a range of linear malto-oligosaccharides
      analysed was 0.13 mM as found at a degree of polymerisation (DP) of 13. Large
      differences in dissociation constants were measured for CDs with DP 6 (alpha-CD,
      6.0 mM), DP 7 (beta-CD, 0.25 mM) and DP 8 (gamma-CD, 0.67 microM). The high
      molecular-mass alpha-glucans amylose and amylopectin, both substrates for PSBE-I,
      showed apparent affinities of 0.018 and 0.066 mg/ml, respectively. Small linear
      and cyclic oligosaccharides competed with amylopectin in the affinity
      electrophoresis system and they were also competitive inhibitors for PSBE-I
      activity. The affinities for oligosaccharides as measured by competition were,
      however, about 10-fold lower than as measured by fluorescence quenching
      suggesting the existence of a separate oligosaccharide binding site on PSBE-I.
      Affinity electrophoresis revealed multiform heterogeneity in the enzyme
      preparation with respect to alpha-glucan interaction.

PMID- 9523706
TI  - Mitochondria and apoptosis.
AB  - Programmed cell death serves as a major mechanism for the precise regulation of
      cell numbers and as a defense mechanism to remove unwanted and potentially
      dangerous cells. Despite the striking heterogeneity of cell death induction
      pathways, the execution of the death program is often associated with
      characteristic morphological and biochemical changes, and this form of programmed
      cell death has been termed apoptosis. Genetic studies in Caenorhabditis elegans
      had led to the identification of cell death genes (ced). The genes ced-3 and ced
      4 are essential for cell death; ced-9 antagonizes the activities of ced-3 and ced
      4, and thereby protects cells that should survive from any accidental activation
      of the death program. Caspases (cysteine aspartases) are the mammalian homologues
      of CED-3. CED-9 protein is homologous to a family of many members termed the Bcl
      2 family (Bcl-2s) in reference to the first discovered mammalian cell death
      regulator. In both worm and mammalian cells, the antiapoptotic members of the Bcl
      2 family act upstream of the execution caspases somehow preventing their
      proteolytic processing into active killers. Two main mechanisms of action have
      been proposed to connect Bcl-2s to caspases. In the first one, antiapoptotic Bcl
      2s would maintain cell survival by dragging caspases to intracellular membranes
      (probably the mitochondrial membrane) and by preventing their activation. The
      recently described mammalian protein Apaf-1 (apoptosis protease-activating factor
      1) could be the mammalian equivalent of CED-4 and could be the physical link
      between Bcl-2s and caspases. In the second one, Bcl-2 would act by regulating the
      release from mitochondria of some caspases activators: cytochrome c and/or AIF
      (apoptosis-inducing factor). This crucial position of mitochondria in programmed
      cell death control is reinforced by the observation that mitochondria contribute
      to apoptosis signaling via the production of reactive oxygen species. Although
      for a long time the absence of mitochondrial changes was considered as a hallmark
      of apoptosis, mitochondria appear today as the central executioner of programmed
      cell death. In this review, we examine the data concerning the mitochondrial
      features of apoptosis. Furthermore, we discuss the possibility that the mechanism
      originally involved in the maintenance of the symbiosis between the bacterial
      ancestor of the mitochondria and the host cell precursor of eukaryotes, provided
      the basis for the actual mechanism controlling cell survival.

PMID- 9523707
TI  - Sorting of invertase signal peptide mutants in yeast dependent and independent on
      the signal-recognition particle.
AB  - There is growing evidence that yeast contains two efficient pathways of protein
      translocation across the endoplasmic reticulum membrane, one dependent on the
      signal-recognition particle (SRP) and the other independent. Their specificity,
      however, is largely obscure. For higher eukaryotes it has been shown that a high
      average hydrophobicity of the core region with a minimal length around six or
      seven amino acids, as well as a stabilized alpha-helix, are decisive structural
      features for translocation. Using yeast invertase as a secretory model protein,
      we have found that mutated signal sequences with Pro or Gly in the core, or
      having only four hydrophobic amino acids, are not functional in translocation
      across microsomal membranes of dog pancreas because they do not interact with the
      SRP. Expression of these mutant variants in Saccharomyces cerevisiae revealed
      that they are sorted independently of the SRP since translocation was not
      impaired in an SRP-deficient yeast strain. In contrast to this, wild-type
      invertase is translocated SRP-dependently in wild-type cells and shows a
      decreased translocation in SRP-deficient cells. By overexpression of Srp54p, but
      not of Hsc70p, the translocation defect of wild-type invertase in an SRP54
      disruptant is restored. The data indicate that targeting of proteins to the
      endoplasmic reticulum in Saccharomyces cerevisiae seems to be more flexible than
      in higher eukaryotes as far as the structural requirements of signal sequences
      are concerned, and that the route taken is specified by the sequence.

PMID- 9523708
TI  - Probing the mechanism of an Mn2+-dependent ribozyme by means of platinum
      complexes.
AB  - The smallest ribozyme system known is the pentanucleotide GAAACp, which is
      specifically cleaved by Mn2+, in the presence of poly(U), generating guanosine
      2',3'-cyclic phosphate and AAACp. A plausible mechanism has been proposed,
      involving the participation of two Mn2+ with structural and catalytic roles, the
      first one cross-linking the two N7 atoms of G1 and A4, and the other binding to
      the N7 atom of A2 and activating the 2'-OH group of G1 [Kazakov, S. & Altman, S.
      (1992) Proc. Natl Acad. Sci. USA 89, 7939-7943]. In the present work, we have
      utilized the high affinity of Pt(II) complexes for N7 atoms of purines in an
      attempt to form a stable active ribozyme by replacing the structural Mn2+ by
      Pt2+. We thus replaced the proposed kinetically labile G1N7-Mn2+-A4N7 cross-link
      by an inert N7-trans-Pt(NH3)(2)(2+)-N7 cross-link. In a complementary
      investigation, the N7 atoms of the individual purines of GAAACp were selectively
      blocked by a Pt(NH3)(3)(2+) residue to determine which of the N7 sites
      participate in the Mn2+-mediated cleavage. Other N7-Pt(II)-N7 crosslinks were
      also investigated. Accordingly, we have prepared four monoadducts, each bearing
      the Pt(NH3)(3)(2+) residue on one of the purines and a series of chelates of
      trans-Pt(NH3)(2)(2+) and cis-Pt(NH3)(2)(2+) and have tested them for Mn2+-induced
      cleavage. Binding of Pt(NH3)(3)(2+) to G1 or A4 did not alter the efficiency of
      the specific cleavage between G1 and A2 catalyzed by Mn2+/poly(U), whereas cross
      linking of G1 and A4 by trans-Pt(NH3)(2)(2+) inhibited it completely. Hence, a
      cross-link between G1 and A4 is not required for the site-specific cleavage.
      Binding of Pt(NH3)(3)(2+) to A2 or A3 strongly inhibits the G1/A2 cleavage,
      suggesting that these bases are likely to be involved in manganese coordination
      in the cleaving complex. A site-specific Mn2+-dependent cleavage between A4 and
      C5 was observed for the G1-A4 and G1-A3 adducts cross-linked by trans
      Pt(NH3)(2)(2+), the G1-A2 adduct cross-linked by cis-Pt(NH3)(2)(2+), and the
      three monoadducts bearing the Pt(NH3)(3)(2+) residue on G1, A2 or A3; poly(U) did
      not exert any influence on this cleavage.

PMID- 9523709
TI  - A detailed analysis of the C5a anaphylatoxin effector domain: selection of C5a
      phage libraries on differentiated U937 cells.
AB  - We have used a phage-display-based system to investigate the effect of
      simultaneous substitutions within the C5a effector domain. Two different
      libraries were constructed. In library I, known binding positions 67, 68, 72 and
      74 of human complement C5a (hC5a) and in library II, positions 69-73 of hC5a
      without C-terminal Arg74 (des-Arg74-C5a) were randomly mutated. In more than 80%
      (position 72) or 90% (positions 68 and 74) of all cases, the original residues of
      hC5a were selected from library I, demonstrating that the phage system can be
      used to define binding points within the C5a molecule. Surprisingly, in more than
      90% of all clones, a Phe residue was enriched at position 67 instead of the
      original His residue which, however, did not affect the binding affinity or the
      signalling activity. In library II, Leu was preferentially selected at positions
      70-72 and Tyr at position 73, while no enrichment of an individual amino acid was
      observed at position 69. Mutants with (a) Leu in positions 71 and 72 (b) Ser or
      Leu in position 70 and (c) Arg or Tyr in position 73, showed a 4-10-fold higher
      binding affinity as compared to des-Arg74-[Ala27, Phe67]C5a. The binding affinity
      was indistinguishable from that of hC5a. In consequence, not only position 72 but
      also positions 70, 71 and 73 are able to interact with the C5a receptor, whereas
      position 69 is not. Intriguingly, one mutant with a high binding affinity but
      without signalling activity was selected. Thus, random mutagenesis of phage
      displayed C5a was proven to be a powerful strategy to define receptor-binding
      points and to select C5aR antagonists based on the structure of the natural
      ligand.

PMID- 9523710
TI  - Kinetics and specificity of reductive acylation of wild-type and mutated lipoyl
      domains of 2-oxo-acid dehydrogenase complexes from Azotobacter vinelandii.
AB  - The kinetics and specificity of reductive acylation of lipoyl domains derived
      from Azotobacter vinelandii 2-oxo-acid dehydrogenase complexes, catalysed by A.
      vinelandii and Escherichia coli complexes, have been investigated. With the wild
      type pyruvate dehydrogenase complex from A. vinelandii the rate of reductive
      acetylation and deacetylation was studied by rapid mixing methods. The rate of
      reductive acetylation, 126 s(-1), corresponds well with the turnover rate derived
      from steady-state measurements. Deacetylation was rapid and specific for coenzyme
      A. No deacetylation was observed with reduced or oxidised lipoamide or with
      dithiothreitol. The rate of reductive acetylation of complex-bound lipoyl domains
      by pyruvate dehydrogenase (E1p) is at least 60 times higher than of free lipoyl
      domains under comparable conditions. This gain in catalytic rate indicates a
      large diffusion limitation of lipoyl domains when attached via the flexible
      linker segments to the complex, and illustrates the efficiency of substrate
      channeling in the multienzyme complex. The 2-oxo-acid dehydrogenases exhibit
      specificity for lipoyl domains in the reductive acylation reaction. The A.
      vinelandii lipoyl domain derived from the pyruvate dehydrogenase complex is a
      good substrate for A. vinelandii E1p, but not for A. vinelandii 2-oxoglutarate
      dehydrogenase (E1o), and vice versa. The A. vinelandii lipoyl domain of the
      pyruvate dehydrogenase complex is also, although at a lower rate, reductively
      acetylated by E. coli E1p and reductively succinylated by E. coli E1o. Likewise,
      the A. vinelandii lipoyl domain derived from the 2-oxoglutarate dehydrogenase
      complex is recognised by E. coli E1o, but not by E. coli E1p. This suggests that
      common determinants of the lipoyl domains exist that are responsible for
      recognition by the E1 components. On the basis of the observed specificity and
      lipoyl domain sequences and structures, an exposed loop of the A. vinelandii 2
      oxoglutarate dehydrogenase complex lipoyl domain was subjected to mutagenesis.
      Although the reductive acylation experiments of mutants of the lipoyl domain
      indicate the importance of this loop for recognition, it is probably not the
      single determinant for specificity.

PMID- 9523711
TI  - Structural studies of histidine-containing phosphocarrier protein from
      Enterococcus faecalis.
AB  - Based on the complete sequential assignment of the 1H-NMR spectrum by
      multidimensional NMR techniques the secondary structure and the local geometry of
      the active site of histidine-containing phosphocarrier protein (HPr) from
      Enterococcus faecalis were elucidated. We present a comparative analysis of the
      active site in the seven known structures of HPr from different organisms
      determined by NMR or X-ray crystallography. In catalysis, HPr is phosphorylated
      at the ring N61 of His15. No general agreement exists in literature regarding the
      structure of the active-centre loop. In the crystal structure of HPr from E.
      faecalis, a torsion strain of the backbone at position 16 was observed, which was
      assumed to be important to the catalytic mechanism. Coupling constants were
      determined in order to calculate phi angles to establish whether there are
      strained torsion angles in HPr from E. faecalis in the solution state. The
      evaluation of data obtained indicate a stable and well-defined structure of HPr
      from E. faecalis, with an overall fold similar to that found in HPr from other
      bacteria. We find that in the active-site region there are relatively large
      variations in local geometry between the evaluated structures. In HPr from E.
      faecalis, a particularly detailed view of the phosphate-binding His15 and
      residues in close spatial proximity was obtained by determination of coupling
      constants obtained from the double-quantum-filtered COSY spectrum. Our data
      indicate that in aqueous solution, in the dominant conformational state there is
      no torsion strain of the backbone at position 16, as observed in the crystal
      state. The maximum population of a strained conformation in solution can be
      estimated to be smaller than 23%. The analysis of the data suggests that the
      active-centre loop is able to adopt different conformations in solution. A
      similar observation was made for HPr from E. faecalis phosphorylated at its
      regulatory site (Ser46). 31P-NMR shows that phosphorylated HPr exists in two
      conformational substates with nearly equal populations.

PMID- 9523712
TI  - Production and purification of active snowdrop lectin in Escherichia coli.
AB  - Recombinant snowdrop lectin was produced in Escherichia coli from a cDNA clone
      encoding mature Galanthus nivalis agglutinin. After induction with isopropylthio
      beta-D-galactoside, inclusion bodies from E. coli were solubilised and the G.
      nivalis agglutinin purified by metal-affinity chromatography using a carboxy
      terminal hexahistidine tag. The protein was refolded on the metal-affinity column
      prior to elution. After purification, the recombinant G. nivalis agglutinin
      agglutinated rabbit erythrocytes to a dilution similar to that determined for
      'native' lectin purified from snowdrop, and showed similar specific binding to
      mannose. The toxicity of the recombinant G. nivalis agglutinin towards rice brown
      planthopper (Nilaparvata lugens) was shown to be similar to that of 'native' G.
      nivalis agglutinin when incorporated into an artificial diet. The recombinant G.
      nivalis agglutinin is thus functionally similar to 'native' snowdrop lectin.

PMID- 9523713
TI  - Heat-induced conformational changes of patatin, the major potato tuber protein.
AB  - This paper presents a first structural characterization of isolated patatin, the
      major potato tuber protein, at ambient and elevated temperatures. Isolated
      patatin at room temperature is a highly structured molecule at both secondary and
      tertiary levels. It is estimated from far-ultraviolet circular dichroism data
      that about 33% of the residues adopts an alpha-helical and 46% a beta-stranded
      structure. Patatin is thermally destabilized at temperatures exceeding 28 degrees
      C, as was indicated by near-ultraviolet circular dichroism. It was shown that
      parts of the alpha-helical contributions unfold in the 45-55 degrees C region,
      whereas the beta-stranded parts unfold more gradually at temperatures of 50-90
      degrees C. This was confirmed with Fourier-transform infrared spectroscopy.
      Differential scanning calorimetry indicated a cooperative transition between 50
      60 degrees C, most likely reflecting the unfolding of alpha-helical parts of the
      molecule. Furthermore, fluorescence spectroscopy confirmed a global unfolding of
      the protein between 45-55 degrees C. The observed unfolding of the protein
      coincides with the inactivation of the patatin enzyme activity and with the
      precipitation as occurs in the potato fruit juice upon heating. At high
      temperatures, patatin still contains some helical and stranded structures. Upon
      cooling the protein partly refolds, it was observed that mainly alpha-helical
      structures were formed.

PMID- 9523714
TI  - A core-shell model of calcium phosphate nanoclusters stabilized by beta-casein
      phosphopeptides, derived from sedimentation equilibrium and small-angle X-ray and
      neutron-scattering measurements.
AB  - Calcium phosphate nanoclusters were prepared under standardised conditions using
      10 mg ml(-1) of the 25-amino-acid N-terminal tryptic phosphopeptide of bovine
      beta-casein as a stabilising agent. The Mr determined by sedimentation
      equilibrium was 197,600+/-13,700 and the apparent radius of gyration determined
      by X-ray scattering was 2.80+/-0.05 nm. A small-angle neutron scattering contrast
      variation study in 1H2O/2H2O mixtures was performed and gave radii of gyration at
      the calculated match points for the calcium phosphate (88.2% 2H2O) and
      phosphopeptide (41.3% 2H2O) of 3.39+/-0.08 nm and 1.85+/-0.05 nm, respectively.
      Measurements at larger scattering wave vector showed a subsidiary maximum at
      about Q = 1.6 nm(-1). The results are consistent with a model of the nanoclusters
      comprising a spherical core of 355+/-20 CaHPO4 x 2 H2O units, density 2.31 g ml(
      1) and radius 2.30+/-0.05 nm surrounded by 49+/-4 peptide chains with a partial
      specific volume of 0.7 cm3 g(-1), forming a tightly packed shell with an outer
      radius of 4.04+/-0.15 nm. This model suggests that the phosphopeptide is able to
      arrest the process of growth of the precipitating phase of calcium phosphate at
      its earliest stages. A similar role for whole casein could be vital to the normal
      functioning of the mammary gland during milk secretion.

PMID- 9523715
TI  - A gene encoding a vicilin-like protein is specifically expressed in fern spores.
      Evolutionary pathway of seed storage globulins.
AB  - The isolation and characterisation of a cDNA coding for a vicilin-like protein of
      the fern Matteuccia struthiopteris is described. The corresponding gene is
      specifically expressed during late stages of spore development. Extensive
      sequence comparisons suggest that the fern protein can be considered as a
      molecular missing link between single-domain germin/spherulin-like proteins and
      two-domain seed storage globulins of gymnosperms and angiosperms. Further,
      evidence is provided for the existence of a superfamily of structurally related,
      functionally different proteins which includes storage globulins of the vicilin
      and legumin families, a membrane-associated sucrose-binding protein of soybean, a
      Forssman antigen-binding lectin of velvet bean, the precursor of the vacuolar
      membrane bound proteins MP27/MP32 of pumpkin, the embryogenesis-specific protein
      Gea8 of carrot, the fern-spore-specific protein described here as well as the
      functionally diverse family of germins/germin-like proteins and the spherulins of
      myxomycetes. We propose that seed storage globulins of spermatophytes evolved
      from desiccation-related single-domain proteins of prokaryotes via a duplicated
      two-domain ancestor that is best represented by the extant fern spore-specific
      vicilin-like protein.

PMID- 9523716
TI  - Glucose oxidase from Penicillium amagasakiense. Primary structure and comparison
      with other glucose-methanol-choline (GMC) oxidoreductases.
AB  - The complete amino acid sequence of glucose oxidase from Penicillium
      amagasakiense was determined by Edman degradation and mass spectrometry of
      peptide fragments derived from three different specific proteolytic digests and a
      cyanogen bromide cleavage. The complete sequence of each monomer comprises 587
      amino acid residues, contains three cysteine residues, and seven potential N
      glycosylation sites, of which at least five were confirmed to be glycosylated.
      Glucose oxidase from P. amagasakiense shows a high degree of identity (66%) and
      79% similarity to glucose oxidase from Aspergillus niger, and is a member of the
      glucose-methanol-choline (GMC) oxidoreductase family. The tertiary structures of
      glucose oxidase from A. niger and cholesterol oxidase from Brevibacterium
      sterolicum were superimposed to provide a template for the sequence comparison of
      members of the GMC family. The general topology of the GMC oxidoreductases is
      conserved, with the exception of the presence of an active site lid in
      cholesterol oxidase and the insertion of additional structural elements in the
      substrate-binding domain of alcohol oxidase. The overall structure can be divided
      into five distinct sequence regions: FAD-binding domain, extended FAD-binding
      domain, flavin attachment loop and intermediate region, FAD covering lid, and
      substrate-binding domain. The FAD-binding and the extended FAD-binding domains
      are composed of several separate sequence regions. The other three regions each
      comprise a single contiguous sequence. Four major consensus patterns have been
      identified, including the nucleotide-binding consensus sequence close to their N
      termini. The functions of the two motifs recently selected by the Genetics
      Computer Group, Madison, Wisconsin, as additional signature patterns of the GMC
      oxidoreductases are discussed. The other consensus patterns belong to either the
      FAD-binding or the extended FAD-binding domain. In addition, the roles of
      conserved residues are discussed wherever possible.

PMID- 9523718
TI  - Fibrin selectivity of the isolated protease domains of tissue-type and vampire
      bat salivary gland plasminogen activators.
AB  - The activity of vampire bat (Desmodus rotundus) salivary plasminogen activator
      (D. rotundus PA alpha1) and to a much lesser extent of tissue-type plasminogen
      activator (t-PA) is stimulated by the presence of fibrin. This cofactor
      requirement has in the past intuitively been attributed to fibrin binding. We
      have previously shown that elements of the non-protease domain of D. rotundus PA
      alpha1 could contribute to fibrin stimulation irrespective of fibrin binding. We
      now demonstrate that the protease domain of D. rotundus PA alpha1 by itself
      exhibits fibrin selectivity, i.e. it is 32-fold stimulated by fibrin but only 1.5
      fold by fibrinogen. To a lesser extent this fibrin selectivity is also shared by
      the protease domain of t-PA. Our findings indicate that protein-protein
      interactions apart from fibrin binding affect the stimulatory mechanism of fibrin
      on D. rotundus PA alpha1 and t-PA.

PMID- 9523717
TI  - The mechanism of porcine pancreatic alpha-amylase. Inhibition of maltopentaose
      hydrolysis by acarbose, maltose and maltotriose.
AB  - A kinetic study was carried out on the inhibitory effects of acarbose, maltose,
      and maltotriose on porcine pancreatic alpha-amylase (PPA), using maltopentaose as
      the substrate. Lineweaver-Burk plots showed that the inhibitory action of
      acarbose is of the mixed non-competitive type. The secondary plots gave straight
      lines. A model involving abortive complexes accounts for these results. Dixon
      plot analysis led to the same conclusion. According to the proposed model, one
      molecule of acarbose per amylase molecule binds either directly to free enzyme at
      the active site or to the enzyme-substrate complex at a secondary carbohydrate
      binding site, which becomes functional after the substrate has bound to the
      enzyme molecule at the active site. Kinetic analysis of the inhibition exerted by
      either the maltose or maltotriose reaction products of maltopentaose hydrolysis
      were then performed. The inhibitory effect of maltose was found to be of the non
      competitive type, while that of maltotriose was competitive. It can therefore be
      concluded that the first reaction product to be released upon maltopentaose
      hydrolysis is maltose, and that the second product is maltotriose. This indicates
      that after hydrolysis of the maltopentaose chain, the reducing side fragment is
      released first.

PMID- 9523719
TI  - A substrate-induced change in the stereospecificity of the serine
      hydroxymethyltransferase-catalysed exchange of the alpha-protons of amino acids-
      evidence for a second catalytic site.
AB  - NMR has been used to study the catalysis of the hydrogen-deuterium exchange of
      the alpha-protons of amino acids by serine hydroxymethyltransferase (EC 2.1.2.1)
      from Escherichia coli. 13C-NMR was used to follow the exchange of the alpha
      protons of [2-13C]glycine. The enzyme-catalysed first-order exchange rate of the
      pro-2S proton of glycine was approximately 7000 times more efficient than that of
      the pro-2R proton of glycine at both pH 7.0 and 7.8. 1H-NMR was used to follow
      the hydrogen-deuterium exchange rates of the alpha-protons of L- and D-2-amino
      derivatives of butyric, pentanoic and hexanoic acids at pH 7.8. Increasing the
      size of the R-group leads to a progressive change in the stereospecificity of the
      exchange reaction from the pro-2S proton of glycine to the 2R proton of L-amino
      acids. The stereospecificity for the alpha-protons of L-amino acids increased as
      the size of the R-group increased. With glycine, removal of tetrahydrofolate led
      to a large decrease in the stereospecificity of the exchange reaction but did not
      affect the exchange rates of the alpha-protons of any of the larger amino acids
      studied. We show that the Schiff base formed between L-2-aminohexanoic acid (L
      norleucine) and pyridoxal 5'-phosphate binds at a different site from the Schiff
      base between glycine and pyridoxal 5'-phosphate. The molecular basis of these
      results is discussed.

PMID- 9523720
TI  - Characterisation of peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase A
      and its N-glycans.
AB  - Peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase A (PNGase A) was
      purified from almonds (Prunus amygdalus var. dulcis). Contrary to previous
      results in the literature, the enzyme appeared to be a heterodimer with subunits
      of 55 and 27 kDa when analysed by SDS/PAGE and two-dimensional electrophoresis.
      Peaks corresponding to molecular masses of 54.2, 21.2 and 75.5 kDa were observed
      with matrix-assisted laser-desorption/ionization mass spectrometry. The N
      terminal sequences of the larger and the smaller chain were determined to be
      LASGYHSWAD and EPTPLHDFPP, respectively. Both polypeptides reacted with
      concanavalin A, indicating their glycoprotein nature. Upon digestion of PNGase
      with pepsin, the N-linked oligosaccharides were released with active PNGase and
      analysed as their 2-aminopyridine derivatives by two-dimensional HPLC and by
      matrix-assisted laser-desorption mass spectrometry. The most abundant N-glycan of
      the four species found exhibited the well known vacuole type structure, i.e. the
      pentasaccharide core with xylose and alpha1,3-linked fucose. The other structures
      either had an additional mannose residue and/or lacked the fucose. PNGase A was
      largely but not absolutely resistant to self-deglycosylation. However, only at an
      extremely high enzyme/substrate ratio, N-glycans released from PNGase A itself
      caused a detectable contamination of a PNGase digest of a glycopeptide.

PMID- 9523721
TI  - Purification and properties of the 5'-3' exonuclease D190-->a mutant of DNA
      polymerase I from Streptococcus pneumoniae.
AB  - A D190-->A mutation was introduced at the 5'-3' exonuclease domain of
      Streptococcus pneumoniae DNA polymerase I by site-directed mutagenesis of the
      polA gene. Comparison of the S. pneumoniae DNA polymerase I, its polymerase
      domain, and the [Ala190]exonuclease mutant revealed that the mutant polypeptide
      retains the polymerase activity of the parental enzyme and displayed the strand
      displacement activity of its polymerase domain. However, introduction of the
      mutation resulted in a 2500-fold reduction of the 5'-3' exonuclease catalytic
      rate compared with the wild-type enzyme. Moreover, the mutation at the Asp190
      residue of the pneumococcal polymerase affected the dependency on metal
      activation of its 5'-3' exonucleolytic activity. These results provide
      experimental support for a direct involvement of this aspartic acid residue in a
      metal-assisted 5'-3' exonucleolytic reaction in type-I-like bacterial DNA
      polymerases and related bacteriophage 5'-3' exonucleases.

PMID- 9523722
TI  - Purification and characterization of N-acetylglucosamine kinase from rat liver-
      comparison with UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase.
AB  - N-Acetylglucosamine, a major sugar in complex carbohydrates, enters the pathways
      of aminosugar metabolism by the action of N-acetylglucosamine kinase (EC
      2.7.1.59). In this study we report the purification to homogeneity of GlcNAc
      kinase from rat liver cytosol using salmine sulfate precipitation, chromatography
      on phenyl-Sepharose, ATP-agarose and MonoQ, and finally gel filtration on
      Superdex 200. It was characterized as a dimer of 39-kDa subunits. About 25% of
      the amino acid sequence of GlcNAc kinase was established by peptide mapping. Part
      of the ATP-binding site of GlcNAc kinase was identified by sequence comparison
      with related hexokinases, including the bifunctional enzyme UDP-N
      acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (EC 5.1.3.14/2.7.1.60),
      the key enzyme of N-acetylneuraminic acid biosynthesis in rat liver. The Cys
      residues in the active sites of GlcNAc kinase and ManNAc kinase were
      characterized by chemical modification with N-ethylmaleimide, iodoacetamide and
      5,5'-dithiobis(2-nitrobenzoic acid). The finding that the substrates GlcNAc and
      ManNAc protected their respective enzymes from inhibition by the above sulfhydryl
      reagents indicates that Cys residues are located in or near the active sites of
      both enzymes. Use of the specific dithiol-modifying chemical reagents, sodium
      meta-periodate, sodium meta-arsenite/2,3-dimercaptopropanol and
      diazenedicarboxylic acid bis-N,N'-dimethylamide revealed that the active sites of
      GlcNAc kinase and ManNAc kinase possess at least one pair of vicinal thiols.
      Chemical treatment of UDP-GlcNAc 2-epimerase provided no evidence for the
      presence of cysteine in the active site of this enzyme. From the incorporation of
      N-[3H]ethylmaleimide into GlcNAc kinase in the absence and presence of ligands we
      estimated that the active site of GlcNAc kinase contains two Cys residues.

PMID- 9523724
TI  - Induction of aromatase activity in human adipose tissue stromal cells by
      extracellular nucleotides--evidence for P2-purinoceptors in adipose tissue.
AB  - Here we describe properties of the P2-purinoceptor, which is involved in the
      regulation of the key enzyme of estrogen biosynthesis, aromatase cytochrome P
      450, in stromal cells from human adipose tissue. Aromatase activity induced by
      cortisol and platelet-derived growth factor BB (PDGF-BB) is further increased by
      addition of ATP, ADP, AMP and, albeit with reduced potency, adenosine, GTP and
      adenosine(5')tetraphospho(5') adenosine. Stable P1-purinoceptor agonists are
      inactive, whereas P2X-purinoceptor agonists mimic the effects of purine(s)
      (nucleotides). Prior incubation of cells with a P2-purinoceptor antagonist, but
      not P1-purinoceptor antagonists, blocks augmentation of aromatase activity by all
      ligands. Nucleotides, but not adenosine, retain their ability to augment
      aromatase activity in the presence of adenosine deaminase, indicating that they
      do not act via their metabolite adenosine. These results lead to the conclusion,
      that at least one member of the P2-subclass of purinoceptors exists in adipose
      tissue and is involved in modulation of aromatase activity in vitro. The
      pharmacological profile of the P2-site differs from those reported for cloned P2
      purinoceptors, but is similar to that of the P2X-subclass. Therefore, a combined
      response of different members of the P2X-purinoceptor subclass or of members of
      different P2-purinoceptor subclasses cannot be discounted. Purinoceptor
      activation triggers cytoplasmic calcium transients, which, in contrast to
      aromatase induction, are independent from the presence of cortisol and PDGF-BB.
      Therefore the involved P2-purinoceptor(s) seem(s) to be constitutively expressed
      in human adipose tissue stromal cells. P2-purinoceptor(s) might provide a direct
      link between sympathetic nerve activity and estrogen biosynthesis in human
      adipose tissue. Furthermore it (or they) may contribute to the regulation of
      lipolysis.

PMID- 9523723
TI  - Comparison of the kinetics of active efflux of 99mTc-MIBI in cells with P
      glycoprotein-mediated and multidrug-resistance protein-associated multidrug
      resistance phenotypes.
AB  - The overexpression of two membrane glycoproteins, P-glycoprotein and multidrug
      resistance protein (MRP1) is a major cause of resistance to chemotherapeutic
      agents in the treatment of human cancers. Both proteins confer a similar
      multidrug-resistant (MDR) phenotype. 99mTc-MIBI, a myocardial imaging agent,
      which is also useful for the detection of a variety of tumours, has been shown to
      be a substrate for P-glycoprotein and MRP1. It thus may provide additional
      information about the P-glycoprotein and MRP1 status of tumour cells. In order to
      obtain information on the substrate specificity of these proteins, we have
      studied the transport kinetics of Tc-MIBI in two cell lines, K562/ADR and
      GLC4/ADR, which overexpress P-glycoprotein and MRP1, respectively. The mean
      active efflux coefficient ka, which is proportional to the ratio of maximal
      efflux rate VM to the apparent Michaelis-Menten constant Km, used to characterise
      the efficiency of the active efflux, was very similar being 1.9 +/- 0.6 x 10(-11)
      s(-1) x cells x ml and 1.3 +/- 0.5 x 10(-11) s(-1) x cells x ml for drug
      resistant K562 and GLC4, respectively. These values are 50-100-times lower than
      for daunorubicin and other anthracycline derivatives, strongly suggesting that
      the efficiency of both transporters to pump Tc-MIBI is by far less than that to
      efflux anthracyclines. Our data show that (a) P-glycoprotein and MRP transporter
      efficiencies to wash out Tc-MIBI are similar, in spite of a different suspected
      mechanism of its transport and (b) that both transporters are less efficient to
      pump Tc-MIBI than to pump anthracyclines (the ka parameter is about 100-times
      lower for TC-MIBI than for anthracycline).

PMID- 9523725
TI  - The N-termini of the alpha and beta subunits at the top of F1 stabilize the
      energy-transfer function in the mitochondrial F1Fo ATP synthase.
AB  - Limited trypsin digestion of isolated F1 removed 15 and 7 amino acids from the N
      termini of the alpha and beta subunits respectively and left other subunits
      untouched as shown by electrophoresis, immunoblotting and protein sequencing. The
      cooperativity for ATP hydrolysis by soluble F1 was impaired by trypsin digestion.
      The Km2 obtained from Eadie-Hofstee plots apparently decreased in trypsin
      digested F1 but the affinity for adenosine 5'-[beta,gamma-imido]triphosphate
      (AdoPP[NH]P) and GTP hydrolysis was not influenced. The inhibition of ATP
      hydrolysis by ADP was attenuated by trypsin digestion. Trypsin digestion of F1
      did not affect its capacity to bind to Fo nor did it alter the sensitivity of ATP
      hydrolysis in the F1Fo reconstituted system to oligomycin and N,N'
      dicyclohexylcarbodiimide. The cleavage of the alpha and beta subunits did, on the
      other hand impair: (a) the ATP-driven proton pumping in the reconstituted F1Fo
      complex: (b) the inhibition by F1 of passive proton conduction in Fo; (c) the
      inhibition of passive proton conduction in Fo by AdoPP[NH]P binding to F1. These
      results show that the limited cleavage of the N-termini of the alpha and beta
      subunits, located on the top of F1, results in decoupling of catalysis from
      proton transport. The possible relationship of these observations with the
      binding change rotatory model of the F1Fo ATP synthase is discussed.

PMID- 9523726
TI  - Negative control of the Mig1p repressor by Snf1p-dependent phosphorylation in the
      absence of glucose.
AB  - Mig1p, a zinc-finger protein that is related to the Krox/Egr, Wilms' tumor and
      Sp1 proteins, mediates glucose repression in the yeast Saccharomyces cerevisiae.
      Mig1p is inactive in the absence of glucose, and this inhibition is dependent on
      the Snf1p (Cat1p) protein kinase. The regulation is mediated by an internal part
      of Mig1p, and it can be transferred to a Mig1-viral protein 16 (VP16) fusion
      protein that functions as an activator [Ostling, J., Carlberg, M. & Ronne, H.
      (1996) Mol. Cell. Biol. 16, 753-761]. We have used Mig1-VP16 to identify three
      target sites for phosphorylation that mediate Snf1p-dependent inhibition of its
      activity in the absence of glucose. Two of the sites, Ser278 and Ser311, fit the
      consensus sequence for phosphorylation by the kinase Snf1p, as determined in
      vitro. However, a third phosphorylated site, Ser108, does not resemble a Snf1p
      site. We tested the effect of deleting residues 181-245, which contain two
      conserved alanine-leucine-serine motifs. We found that the deletion produces a
      partially constitutive activator, indicating that this region plays a general
      negative role in regulating Mig1p.

PMID- 9523727
TI  - Characterization of a gene that is inversely correlated with estrogen receptor
      expression (ICERE-1) in breast carcinomas.
AB  - Differential display was used to compare patterns of gene expression in two
      estrogen receptor (ER)-positive breast carcinoma cell lines (MCF7 and T-47D) and
      two ER-negative breast carcinoma cell lines (MDA-MB-231 and HBL-100). A 377-bp
      fragment was identified that was overexpressed in the ER-negative cell lines.
      Sequence analysis of this clone and comparison with the GenBank/EMBL databases
      indicated that it did not match any genes published previously. The expression
      pattern of this gene was inversely correlated with the expression of ER and has
      been termed ICERE-1 (inversely correlated with estrogen receptor expression). A
      longer clone of ICERE-1 was isolated from a MDA-MB-231 cDNA library and sequence
      analysis indicated that this 2168-bp cDNA contained an ORF encoding a protein of
      234 amino acids that bears little similarity with any previously described
      protein sequence. Northern blot analysis of a panel of breast cancer cell lines
      demonstrated that an ICERE-1 mRNA of approximately 2.2 kb was abundantly
      expressed in the ER-negative breast carcinoma cell lines, MDA-MB-231 and HBL-100,
      and the ER-negative cell lines. HEC-1-B, HeLa, and 293. Expression of ICERE-1 was
      absent or minimal in the ER-positive breast carcinoma cell lines MCF7, T-47D, MDA
      MB-361, ZR-75-1, BT-474 and BT-20. Reverse transcription/PCR was used to examine
      ICERE-1 expression in 29 primary breast carcinomas, 15 of which had been
      designated as ER positive and 14 as ER negative by immunohistochemistry. The
      expression level of ICERE-1 was significantly lower (P < 0.001) in the ER
      positive tumors compared with the ER-negative tumors. The pattern of expression
      of ICERE-1 indicates that this gene may be involved in tumor biology specific to
      hormonally unresponsive breast cancers.

PMID- 9523728
TI  - Transient up-regulation of a prolyl endopeptidase activity in the microsomal
      fraction of rat liver during postnatal development.
AB  - To identify proteases which are involved in cell proliferation and
      differentiation of liver cells, we assayed various protease activities in rat
      liver during its postnatal development. We found that a protease activity
      specific to proline residues in the microsomal fraction of rat liver was
      transiently increased around postnatal day 8 and decreased thereafter, indicating
      that the enzyme activity is highly correlated to the proliferation and
      differentiation of liver cells. This protease was purified to an apparent
      homogeneity from the microsomal fraction of the postnatal-day-8 rat liver. The
      purified enzyme gave a single band with an apparent molecular mass of 65,000 on
      SDS/PAGE. It cleaved several peptide 4-methylcoumaryl-7-amide substrates and
      bioactive peptides at the C-terminus of proline residues. The enzyme did not
      hydrolyze any protein substrate examined suggesting that it is a peptidase rather
      than a proteinase. Although the best substrate among those tested was succinyl
      Gly-Pro-Leu-Gly-Pro-4-methylcoumaryl-7-amide (-NH-Mec), the purified enzyme did
      not hydrolyze succinyl-Gly-Pro-NH-Mec, indicating that the enzyme has different
      substrate specificity from any hitherto known prolyl endopeptidases. These
      results suggest that the purified enzyme is a unique prolyl endopeptidase which
      may be involved in proliferation and differentiation of liver cells.

PMID- 9523729
TI  - Pharmacokinetic behavior of vincristine sulfate following administration of
      vincristine sulfate liposome injection.
AB  - The pharmacokinetic behavior of vincristine sulfate (VINC) following
      administration of vincristine sulfate liposome injection (VSLI), 0.16 mg/ml, as
      an intravenous infusion over 60 min in 24 of 25 patients enrolled in a phase I
      clinical study of this drug is described. Plasma samples for determination of the
      pharmacokinetic behavior of VINC were collected during the infusion at 15, 30 and
      60 min as well as at 2, 4, 8, 12, 48 and 72 h postinfusion. Total VINC
      concentration was determined using a validated high-performance liquid
      chromatographic (HPLC) assay. Patients receiving doses of 0.5 to 1.5 mg/m2 VSLI
      did not provide useful pharmacokinetic data at late time-points owing to the
      limit of quantitation of the HPLC assay (28.6 ng/ml). Sufficient concentration
      time data were available for seven of the patients receiving doses of VSLI from
      2.0 to 2.8 mg/m2 for compartmental modelling. A two-compartment open model
      (PCNONLIN Model 10) was the best fit for the observed VINC plasma data for these
      patients. The mean maximum observed concentration values were significantly
      greater for patients receiving VSLI at 2.8 mg/m2 (2260 +/- 212 ng/ml, n = 2) than
      for those receiving 2.0 mg/m2 and 2.4 mg/m2 (891 +/- 671 ng/ml, n = 6; 679 +/-
      634 ng/ml, n = 6, respectively). No significant differences were observed in
      maximum concentration values between patients at 2.0 mg/m2 and those at 2.4
      mg/m2. A trend towards higher parametric AUC (0 to infinity) values with
      increasing dose (on a milligram per meter squared basis) was observed but
      statistical significance was not reached. Comparison of the pharmacokinetic
      behavior of VSLI observed in this study with nonencapsulated VINC demonstrated
      that (1) the variability observed for VSLI pharmacokinetic parameters was similar
      to nonencapsulated VINC, (2) although variability in absolute concentration was
      observed between patients, the behavior of VSLI in individual patients followed a
      two- rather than a three-compartment open model, and (3) VINC plasma
      concentrations were significantly greater following administration of VSLI than
      described for nonencapsulated VINC. Overall, the results for patients treated
      with VSLI from 2.0 to 2.8 mg/m2 suggest that this formulation protects VINC from
      the early phase of rapid elimination seen with nonencapsulated drug, resulting in
      significantly elevated VINC plasma concentrations over extended periods of time.

PMID- 9523730
TI  - Reduced activity of topoisomerase II in an Adriamycin-resistant human stomach
      adenocarcinoma cell line.
AB  - A human stomach-adenocarcinoma cell line (MKN-45) was selected for resistance to
      Adriamycin by stepwise exposure to increasing concentrations of this agent. The
      resulting cell line (MKN/ADR) exhibited a high level of cross-resistance to
      topoisomerase II (topo II)-targeted drugs such as Adriamycin, mitoxantrone, and
      etoposide but showed no cross-resistance to other chemotherapeutic agents such as
      cisplatin, carboplatin, 5-fluorouracil, or mitomycin-C. P-glycoprotein encoded by
      the mdr-1 gene was not overexpressed in the MKN/ADR cell line. The doubling time
      of the MKN/ADR cell line (2.1 days) increased only slightly as compared with that
      of the MKN cell line (1.7 days). The patterns of cross-resistance to various
      chemotherapeutic agents led us to examine the cellular contents of topo II in
      both the drug-sensitive and the drug-resistant cells. Extractable topo II enzyme
      activity was 3-fold lower in MKN/ADR cells as compared with the parental MKN
      cells. Levels of topoisomerase I (topo I) catalytic activity were similar in both
      wild-type MKN and drug-resistant MKN/ADR cells. Southern-blot analysis of genomic
      DNA probed with topo IIalpha or IIbeta showed no sign of either gene
      rearrangement or hypermethylation. Northern-blot analysis revealed that both topo
      IIalpha and topo IIbeta mRNA transcripts were essentially identical in the MKN
      and MKN/ADR cells. In contrast, Western-blot analysis revealed an approximately
      20-fold lower level of topo IIalpha in drug-resistant cells as compared with drug
      sensitive cells, whereas topo IIbeta levels were similar in both lines. Moreover,
      the amount of in vivo topo IIalpha-DNA covalent complexes formed in the presence
      of etoposide was also approximately 20-fold lower in drug-resistant cells. No
      mutation was detected in the promoter region of the topo IIalpha gene in
      resistant cells as compared with sensitive cells. Thus, low levels of topo
      IIalpha polypeptide cannot be ascribed to changes in the mRNA levels.
      Collectively, the data suggest that a quantitative reduction in topo IIalpha may
      contribute to the resistance of MKN cells to Adriamycin and other topo II
      targeted drugs.

PMID- 9523731
TI  - Induction of DNA damage, inhibition of DNA synthesis and suppression of c-myc
      expression by the anthracycline analog, idarubicin (4-demethoxy-daunorubicin) in
      the MCF-7 breast tumor cell line.
AB  - PURPOSE: Studies were designed to elucidate the basis for the antiproliferative
      activity of the anthracycline antibiotic, idarubicin (4-demethoxy-daunorubicin)
      in MCF-7 breast tumor cells. METHODS: Growth inhibition was evaluated using the
      MTT tetrazolium dye assay, induction of DNA strand breaks was determined by
      alkaline elution, inhibition of DNA synthesis was assessed by measuring the
      incorporation of labelled thymidine into DNA, modulation of the expression of the
      c-myc oncogene was determined by Northern blotting and the induction of apoptosis
      was evaluated by alkaline unwinding, static field gel electrophoresis, terminal
      end labelling and assessment of cell morphology. RESULTS: MCF-7 cells were
      relatively sensitive to idarubicin, with an IC50 value for growth inhibition of
      approximately 0.01 microM. While DNA strand breakage was not evident below a
      concentration of 0.1 microM idarubicin, where growth inhibition exceeded 70%,
      both the inhibition of DNA synthesis and suppression of c-myc expression closely
      paralleled the profile of antiproliferative activity for idarubicin. Finally,
      while exposure to idarubicin resulted in a substantial loss of viable cells
      within 48-72 h, there was no morphological evidence of apoptotic body formation.
      The absence of apoptosis in cells exposed to idarubicin was supported by studies
      demonstrating the absence of DNA fragmentation using gel electrophoresis,
      alkaline elution and in situ DNA end-labelling assays. CONCLUSIONS: The results
      of these studies extend previous results from this laboratory indicating an
      association between suppression of c-myc expression, inhibition of DNA synthesis
      and growth arrest by topoisomerase II inhibitors, as well as the lack of
      induction of apoptotic cell death by topoisomerase II inhibitors in MCF-7 breast
      tumor cells.

PMID- 9523732
TI  - Investigation of the enterohepatic recirculation of Adriamycin and its
      metabolites by a linked-rat model.
AB  - We investigated the possible role of enterohepatic recirculation in prolongation
      of the half-life of elimination for Adriamycin, a commonly prescribed anticancer
      agent. We sought to determine whether enterohepatic recirculation of Adriamycin
      and its metabolites occurs using a linked-rat model. Two rats, a donor and a
      receiver, were linked via a catheter from the bile duct of the donor rat to the
      duodenum of the receiver. Control experiments were conducted with intact rats
      (without a bile duct cannula, control A) in order to estimate the half-life of
      elimination and with bile duct-cannulated rats (control B) to determine the
      amounts of Adriamycin and its metabolites in the bile. [14C-14]-Adriamycin was
      injected intravenously via the femoral vein to control A, control B and donor
      rats. The biological half-life of Adriamycin in the intact rats (control A, 10 h)
      was significantly higher than in the bile-duct-cannulated rats (control B, 4 h).
      The cumulative amount of Adriamycin and its metabolites excreted in the urine of
      the control A rats was also greater than from control B rats, indicating higher
      levels of the drug in their systemic circulation. Biological samples (bile,
      urine, plasma, blood cells and the major organs heart, liver and kidney) of the
      receivers contained significant amounts of Adriamycin and its metabolites. The
      total radioactivity recovered in the bile of the receivers accounted for 0.1% to
      8% of the Adriamycin dose that was administered to the donors. Adriamycin and its
      metabolites appeared there only after a lag time that was consistent among all
      the receivers. Doxorubicinol aglycone was the major metabolite found in the bile
      and urine of the receivers. Low but constant levels of radioactivity were also
      detected in the plasma and blood cells of the receivers. The presence of
      unchanged Adriamycin in the bile and urine of the receivers suggested absorption
      of the parent drug from the intestine of the receivers. Overall, we estimated
      that about 22% of the dose injected to the donors was absorbed from the intestine
      of the receivers. Taken together, these findings clearly demonstrate a
      significant role for enterohepatic recirculation of Adriamycin and its
      metabolites, which may contribute to the ability of these compounds to induce
      cumulative cardiac damage and/or to increase the efficacy of Adriamycin.

PMID- 9523733
TI  - A clinical pharmacokinetics study of carzelesin given by short-term intravenous
      infusion in a phase I study.
AB  - We investigated the pharmacokinetic behavior of carzelesin in 31 patients
      receiving this drug by 10-min intravenous infusion in a Phase I clinical trial,
      which was conducted at institutions in Nijmegen (institution 1) and Brussels
      (institution 2). The dose steps were 24, 48, 96, 130, 150, 170, 210, 250, and 300
      microg/m2. Carzelesin is a cyclopropylpyrroloindole prodrug that requires
      metabolic activation via U-76,073 to U-76,074. The lower limit of quantitation
      (LLQ) of the high-performance liquid chromatography (HPLC) method used in this
      study was 1 ng/ml for the parent drug and its metabolic products. Carzelesin was
      rapidly eliminated from plasma (elimination half-life 23 +/- 9 min; mean value +/
      SD). At all dose levels, U-76,073 was found as early as in the first samples
      taken after the start of the infusion. However, the concentration of U-76,074
      exceeded the LLQ for only short periods and only at the higher dose levels.
      Although the plasma levels of all three compounds were well above the respective
      IC50 values obtained by in vitro clonogenic assays, they were much lower than
      those observed in a preclinical study in mice. There was a substantial
      discrepancy in the mean plasma clearance observed between patients from
      institution 1 (7.9 +/- 2.1 l h[-1] m[-2]) and those from institution 2 (18.4 +/-
      13.6 l h[-1] m[-2]; P = 0.038), probably reflecting problems with drug
      administration in the latter institution. The results recorded for patients in
      institution 1 indicated that the AUC increased proportionately with increasing
      doses. There was a good correlation between the maximal plasma concentration and
      the AUC, enabling future monitoring of drug exposure from one timed blood sample.
      Urinary excretion of carzelesin was below 1% of the delivered dose.

PMID- 9523734
TI  - In vitro and in vivo interaction between cisplatin and topotecan in ovarian
      carcinoma systems.
AB  - Topotecan, a camptothecin analogue, is a specific inhibitor of topoisomerase I
      approved for use in the treatment of patients with refractory ovarian carcinoma.
      The drug's mechanism of action suggests a potential efficacy of drug combinations
      incorporating DNA-damaging agents. In an attempt better to define a rational
      basis for drug combination we examined the effect of topotecan on the
      cytotoxicity and antitumor activity of cisplatin in an ovarian carcinoma system
      growing in vitro and in vivo as a tumor xenograft. The in vitro cell system
      included a cisplatin-sensitive cell line, IGROV-1, and a cisplatin-resistant
      subline, IGROV-1/Pt0.5, which is characterized by p53 mutation and loss of normal
      function of the wild-type gene of the parental cell line. This cell system was
      chosen since the cell sensitivity to DNA-damaging agents appears to be dependent
      on p53 gene status. Cytotoxicity was assessed by the growth inhibition assay
      using different schedules: (a) a 1-h period of cisplatin exposure followed by a
      24-h topotecan treatment and (b) a 1-h period of simultaneous exposure to
      cisplatin and topotecan. In the case of the sequential schedule, an additive
      interaction was observed in IGROV-1 and IGROV-1/Pt0.5 cells. When the
      simultaneous schedule was used, a synergistic interaction, more evident for the
      cisplatin-sensitive cells, was found. On the basis of these observations at a
      cellular level, the effect of concomitant administration of the two drugs (i.e.,
      the most favorable schedule) was studied in the IGROV-1 tumor xenograft, which is
      moderately responsive to cisplatin and topotecan. Suboptimal doses of each drug
      (with a low dose of topotecan, 5.1 mg/kg) achieved an antitumor effect comparable
      with or superior to that of the optimal dose of a single treatment (tumor weight
      inhibition, 60%), thus indicating a pharmacological advantage of the combination
      over the single treatment. However, an increase in the topotecan dose (7.1 mg/kg)
      was associated with an evident increase in the toxicity of the combination,
      thereby suggesting that the drug interaction was not tumor-specific. Although the
      molecular basis of the drug interaction is not clear, it is likely that
      inhibition of topoisomerase I affects the ability of cells to repair cisplatin
      adducts. Such findings may have pharmacological implications since they suggest
      the potential clinical interest of topoisomerase I inhibitors in combination with
      cisplatin.

PMID- 9523735
TI  - Identification of the structural region of taxol that may be responsible for
      cytokine gene induction and cytotoxicity in human ovarian cancer cells.
AB  - PURPOSE: Interleukin-8 (IL-8) is a pleiotropic chemokine with both
      chemoattractant and angiogenic properties. In addition to its cytotoxic effects
      on ovarian cancer cells, taxol can transcriptionally activate genes such as IL-8
      that may play a role in tumorigenesis. Utilizing IL-8 as a prototypic marker of
      tumor-derived modulators of growth, we undertook a systematic study of taxol and
      11 structurally modified taxol analogs to identify the region of the taxane
      skeleton responsible for IL-8 gene induction. METHODS: The human ovarian cancer
      cell line OVCA-420 was exposed to taxol or taxol analogs. IL-8 gene induction was
      assessed by Northern blot analysis after 6 h and cytotoxicity after 72 h.
      RESULTS: Changes in the southern hemisphere (C-1 to C-4) of the taxane skeleton
      had greater effects on IL-8 induction than changes in the northern hemisphere (C
      7 to C-11). Some of the taxol analogs modified at positions C-1 and/or C-2 with
      increased hydrophobicity induced IL-8 expression more than threefold over that
      induced by taxol or taxotere and more than 20-fold over control cells. Cells that
      failed to induce IL-8 gene expression in response to taxol were only marginally
      responsive to the analogs unless first primed with IL-1beta. Modifications to the
      northern hemisphere did not alter taxol's effect on IL-8 expression in human
      cells, but did influence TNFalpha expression in murine macrophage cells,
      suggesting species and/or gene specificity. We found a direct correlation between
      IL-8 induction and cytotoxicity, in that analogs that dramatically upregulated IL
      8 expression proved to be the most cytotoxic, inhibiting cell survival by > 90%.
      CONCLUSION: Taken together our results demonstrate that changes in the southern
      hemisphere of the taxane skeleton influence both the gene induction and cytotoxic
      potential of taxol in human ovarian cancer cells.

PMID- 9523736
TI  - The mechanism of polyamine analog-induced enhancement of cisplatin cytotoxicity
      in the U-251 MG human malignant glioma cell line.
AB  - PURPOSE: During the last decade, several polyamine analogs have been developed as
      antineoplastic agents that replace intracellular polyamines but cannot mimic the
      biological functions of polyamines related to cell growth. It has been shown that
      pretreatment of several human brain tumor cell lines with some of these polyamine
      analogs increases the cytotoxicity of cis-diamminedichloroplatinum (CDDP). It has
      also been established that some of these polyamine analogs affect chromatin
      organization. In the study reported here we attempted to elucidate the mechanism
      by which polyamine analog-induced changes in DNA and chromatin structure may
      increase CDDP cytotoxicity. METHODS: We studied the micrococcal nuclease
      sensitivity of the nuclei and measured the amount of platinum incorporated into
      the nucleosomal and linker regions of chromatin isolated from CDDP-treated U-251
      MG human malignant brain tumor cells with or without pretreatment with two
      cytotoxic polyamine analogs 1,11-bis(ethylamino)-4,8-diazaundecane (BE-3-3-3) and
      1,19-bis(ethylamino)-5,10,15-diazanonadecane (BE-4-4-4-4). RESULTS: The
      pretreatment with the polyamine analogs decreased the MNase sensitivity and
      increased the incorporation of CDDP preferentially into the linker region of the
      chromatin. CONCLUSIONS: Pretreatment of cells with polyamine analogs probably
      alters the structure and/or the organization of the linker region such that more
      CDDP incorporates into the linker DNA. This is probably the reason for the
      observed enhancement of CDDP cytotoxicity in the polyamine analog-pretreated
      cells.

PMID- 9523737
TI  - Gemcitabine induces programmed cell death and activates protein kinase C in BG-1
      human ovarian cancer cells.
AB  - PURPOSE: Cytosine arabinoside induces apoptosis and this cell death process is
      influenced by protein kinase C signaling events in leukemic cells. We present
      findings that extend these observations to include another deoxycytidine analog,
      gemcitabine, which is more potent in solid tumors. METHODS AND RESULTS:
      Gemcitabine induced programmed cell death in BG-1 human ovarian cancer cells
      based on biochemical and morphologic analyses. The DNA was fragmented in BG-1
      cells exposed to gemcitabine (0.5 microM, 1.0 microM and 10 microM) for 8 h, but
      gemcitabine treatment did not induce internucleosomal DNA degradation. Scanning
      and transmission electron microscopy of BG-1 cells showed morphologic changes
      associated with apoptosis in response to gemcitabine: membrane blebbing, the
      formation of apoptotic bodies and chromatin condensation. Thus, BG-1 cells
      undergo programmed cell death in response to gemcitabine treatment without
      internucleosomal DNA fragmentation. Furthermore, gemcitabine (10 microM)
      activated protein kinase C in BG-1 cells and the phosphorylation of the
      endogenous protein kinase C substrate, myristoylated alanine-rich C kinase
      substrate, was increased following exposure of BG-1 cells to gemcitabine for up
      to 6 h. Clonogenicity studies with gemcitabine in combination with various
      protein kinase C-modulating agents demonstrated that gemcitabine cytotoxicity was
      influenced by protein kinase C signaling events in BG-1 cells. Short-term (1 h)
      exposure to TPA (1 or 10 nM) followed by gemcitabine (0.5 microM for 4 h) did not
      alter the response to gemcitabine. However, a 24-h exposure to TPA followed by
      gemcitabine resulted in synergistic cytotoxicity, while coincubation of TPA with
      a PKC inhibitor (e.g. bisindolylmaleimide or calphostin-C) in this regimen
      abrogated the synergistic response. CONCLUSIONS: Based on our findings, it is
      plausible that gemcitabine therapy could be improved by modulating PKC signaling
      events linked to drug-induced apoptosis/cytotoxicity.

PMID- 9523738
TI  - Acute changes in urine protein excretion may predict chronic ifosfamide
      nephrotoxicity: a preliminary observation.
AB  - PURPOSE: To evaluate proteinuria occurring early after ifosfamide therapy and to
      assess the use of changes in proteinuria in the prediction of severe chronic
      nephrotoxicity. METHODS: One-dimensional sodium dodecyl sulphate polyacrylamide
      gel electrophoresis was used to characterize urine protein excretion in 12
      children with solid tumours before and after the first course of ifosfamide
      treatment, and in 24 healthy children. Chronic nephrotoxicity was evaluated at 6
      months after ifosfamide treatment and graded as none, mild, moderate or severe.
      RESULTS: Urine from healthy children and from 10 of 12 patients before ifosfamide
      therapy showed a protein band with a molecular weight (95.4 kDa) corresponding to
      that of Tamm-Horsfall protein but no lower molecular weight proteins. After the
      first course of ifosfamide this 95.4-kDa protein was lost in six of ten patients
      with a concomitant appearance of a low molecular weight proteinuria (< 70 kDa) in
      eight. Tamm-Horsfall protein was lost in two of five patients who subsequently
      developed no or mild nephrotoxicity and in four of five patients who subsequently
      developed moderate or severe nephrotoxicity. CONCLUSIONS: Early subclinical
      changes in urine protein excretion after ifosfamide, manifested by a loss of Tamm
      Horsfall protein excretion, may be predictive of subsequent chronic
      nephrotoxicity.

PMID- 9523739
TI  - Geldanamycin-induced cytotoxicity in human colon-cancer cell lines: evidence
      against the involvement of c-Src or DT-diaphorase.
AB  - We investigated two of the major proposed modes of action of the benzoquinoid
      ansamycin geldanamycin using a pair of human colon-carcinoma cell lines, BE and
      HT29. One potential mechanism of action in colorectal cancer is the inhibition of
      c-Src kinase activity, since this proto-oncogene is hyperexpressed in human large
      bowel tumours. Our results show that despite the 9-fold higher level of c-Src
      kinase activity found in HT29 cells, there was only a 1.4-fold difference in
      cytotoxicity as compared with BE cells, the latter being the most sensitive.
      Moreover, even at concentrations of geldanamycin that resulted in cell kill of
      80% or more after a 24-h period of exposure, there was no effect on c-Src kinase
      activity in HT29 cells, although c-Src protein was depleted at supralethal levels
      of exposure. We also investigated the metabolism of the quinone moiety of
      geldanamycin by DT-diaphorase, an enzyme that activates certain quinone
      antibiotics such as mitomycin C and is hyperexpressed in colorectal cancer cells.
      Geldanamycin was shown to be a substrate for DT-diaphorase present in HT29 cells.
      However, the lack of a major differential in cytotoxicity between HT29 and BE
      cells indicates that this is unlikely to be pharmacologically significant, since
      the former contains high levels of enzyme activity, whereas BE cells have no
      significant activity due to a point mutation in the DT-diaphorase (NQO1) gene.
      Although reduction of geldanamycin was also catalysed by non-DT-diaphorase
      reductases in HT29 and BE cells, providing the potential for free radical
      induction, this is unlikely to be significant since studies previously reported
      by us elsewhere showed that cells exposed to geldanamycin exhibited no evidence
      of DNA damage. Thus, as far as the mode of action of geldanamycin in human colon
      carcinoma cells is concerned, the present results rule out two major
      possibilities, namely, the involvement of c-Src tyrosine kinase inhibition and DT
      diaphorase metabolism.

PMID- 9523740
TI  - Effect of filgrastim on the pharmacokinetics of MX2 hydrochloride in patients
      with advanced malignant disease.
AB  - PURPOSE: To investigate the effect of granulocyte colony-stimulating factor (G
      CSF) on the pharmacokinetics and pharmacodynamics of the new morpholino
      anthracycline drug MX2. METHODS: A total of 25 patients with advanced malignant
      disease participated in a dose-escalation study in the first cycle of treatment
      given i.v. at doses of 50-80 mg/m2 (74-152 mg) with concomitant filgrastim (G
      CSF, 5 microg/kg) given daily beginning at 24 h after the dose of MX2. RESULTS:
      The mean fast distribution half-life (1.5 +/- 1.0 min) and the mean plasma
      clearance (2.18 +/- 0.95 l/min) were significantly lower than the respective mean
      values found in a previous study in which 27 patients had received MX2 (16.8
      107.5 mg) alone (3.3 +/- 2.2 min and 2.98 +/- 1.68 l/min, respectively; P <
      0.05). There was no correlation between plasma clearance and the delivered dose
      for the combined MX2-alone and MX2-filgrastim groups, indicating that the lower
      clearance observed in the G-CSF group was probably not due to the higher dose.
      Elimination half-lives of the metabolites M1 and M4 were significantly greater in
      the filgrastim group (19.8 +/- 14.7 and 11.8 +/- 5.0 h for M1 and 14.8 +/- 4.1
      and 12.3 +/- 6.3 h for M2, respectively). Unlike the MX2-alone group, there was
      no relationship in the MX2-filgrastim group between the relative nadir neutrophil
      count and the dose or between the duration of grade IV neutropenia and the dose
      of MX2. CONCLUSIONS: This study shows that filgrastim decreased the plasma
      clearance of MX2 by approximately 25%, possibly by inhibition of metabolism.

PMID- 9523741
TI  - Progression of Parkinson's disease with impairment of vision under
      carboplatin/cyclophosphamide therapy for ovarian cancer.

PMID- 9523742
TI  - Recent advances in the treatment of idiopathic thrombocytopenic purpura: the anti
      D clinical experience.

PMID- 9523743
TI  - Idiopathic thrombocytopenic purpura: A concise summary of the pathophysiology and
      diagnosis in children and adults.
AB  - Idiopathic thrombocytopenic purpura (ITP) is a disorder that has distinct
      clinical manifestations in children and adults. In children, ITP is typically
      abrupt in onset and self-limited in its course. Girls and boys are equally
      affected. In adults, ITP is typically more indolent in its onset and the course
      is persistent, often lasting many years or characterized by recurrent
      exacerbations of disease. Most patients are young women. Intracerebral
      hemorrhage, while rare, is the most common cause of death in children and adults
      with ITP. In both children and adults, the ITP is assumed to be caused by
      antibody-mediated platelet consumption, where Fc receptors on the macrophage bind
      to antibody-coated platelets resulting in an accelerated platelet destruction.
      However, tests for antiplatelet antibodies have not yet been established as
      clinically useful for management decisions. The natural history and long-term
      prognosis of adults with ITP remain incompletely defined.

PMID- 9523744
TI  - Safety profile of WinRho anti-D.
AB  - WinRho anti-D is manufactured with multiple processes to minimize the risk of
      transmitting blood-borne diseases such as viruses. These safety features include
      donor selection, plasma testing, solvent-detergent viral inactivation, and
      nanofiltration. To date, there has not been any case of viral transmission in
      association with use of WinRho anti-D. Adverse drug reactions are infrequent and
      generally mild; the most common are headache, fever, and chills. Some degree of
      hemolysis is inevitable due to the mechanism of action of WinRho anti-D, but this
      is predictable and transient. A few cases of intravascular hemolysis have been
      reported; hypersensitivity reactions are very rare. WinRho anti-D has been shown
      in both clinical trials and postmarketing surveillance to be safe and effective
      in the treatment of idiopathic thrombocytopenic purpura (ITP) and in the
      prevention of Rh isoimmunization.

PMID- 9523745
TI  - Anti-D: mechanisms of action.
AB  - Immunoglobulin that recognizes and binds specifically to the erythrocyte D
      antigen (anti-D globulin, WinRho SDF; Nabi, Boca Raton, FL) has recently been
      shown to be an effective therapy for many patients with idiopathic
      thrombocytopenic purpura (ITP). Its mechanisms of action are not completely
      understood. Intravenous (IV) infusion of anti-D into a D-positive recipient leads
      to antibody coating of circulating erythrocytes that are cleared primarily by the
      spleen. This immune-mediated clearance of sensitized erythrocytes occupies the
      reticuloendothelial system and allows survival of antibody-coated platelets.
      Based on clinical observations, experimental data, and theoretical calculations,
      the efficacy of anti-D therapy in ITP depends on several factors that influence
      the amount of erythrocyte sensitization and the rate of immune-mediated
      erythrocyte clearance by the spleen. Antibody characteristics, including the
      antibody concentration, binding affinity, and dissociation constants, may be
      important, as well as the number of D-antigen binding sites on the erythrocytes.
      Although the primary mechanism of action of anti-D is believed to be immunologic
      blockade of Fc receptors (FcR) within the reticuloendothelial system (RES), other
      immunomodulatory effects are also possible.

PMID- 9523746
TI  - Efficacy, safety, and dose response of intravenous anti-D immune globulin (WinRho
      SDF) for the treatment of idiopathic thrombocytopenic purpura in children.
AB  - We analyzed data from 20 children treated for acute or chronic idiopathic
      (immune) thrombocytopenic purpura (ITP) at a single institution to determine the
      relationship between dose of intravenous anti-D immune globulin (WinRho SDF;
      Nabi, Boca Raton, FL), increase in platelet count, and decrease in hemoglobin in
      the therapy of ITP. Higher doses of anti-D were clearly associated with a greater
      therapeutic response in the platelet count, with no increase in hemolysis for
      both acute and chronic ITP. A significant correlation was found between dose and
      peak increase in platelet count measured in the 14 days following administration.
      This effect was present for both acute ITP (17 infusions, P = .0001) and chronic
      ITP (30 infusions, P = .038). Although hemolysis was seen in nearly all
      infusions, with a median hemoglobin fall of 1.9 g/dL (range, 0 to 4.2), the
      decrease in hemoglobin was greater than 2.5 for only three infusions, and the
      largest fall in hemoglobin (4.2) was in a child with an underlying hemolytic
      anemia. Furthermore, for both acute and chronic ITP there was no relationship
      between the decrease in hemoglobin and the dose given (P = .22), nor between the
      increase in platelet count and fall in hemoglobin (P = .27). This analysis
      supports the use of higher doses of anti-D for the treatment of ITP, and
      demonstrates the need for a trial of high-dose anti-D (>100 microg/kg) in acute
      and chronic ITP.

PMID- 9523747
TI  - Treatment of acute immune thrombocytopenic purpura.
AB  - Medical history, physical examination, and laboratory testing are essential to
      arriving at the diagnosis of acute immune thrombocytopenic purpura (ITP). A
      history of recent viral illness occurs in about half of the pediatric patients
      who present with acute symptoms of ITP. The physical examination is normal except
      for purpura; a complete blood cell count with a differential white blood cell
      count can be used to confirm the diagnosis of acute ITP. Treatment decisions for
      acute ITP remain controversial. Treatment generally is designed to prevent life
      threatening complications, such as intracranial hemorrhage, and may include
      single or combination therapy with corticosteroids, intravenous immunoglobulin
      (IVIg), anti-D, and splenectomy. Corticosteroids are inexpensive and offer an
      alluring option, especially in the recent era of cost-containment. The often slow
      platelet response and the potentially severe adverse effects of corticosteroid
      therapy are frequently a deterrent. IVIg usually leads to a rapid rise in
      platelet count; however, IVIg is very expensive and adverse effects associated
      with its infusion are common and sometimes troublesome. The role of anti-D in
      acute ITP is still evolving. It is similar to IVIg in platelet response and is
      considerably less expensive. Some degree of hemolysis, the main adverse reaction
      with anti-D, is inevitable due to the binding of anti-D antibody to Rh-positive
      erythrocytes. However, most cases of hemolysis do not require medical
      intervention. Splenectomy is reserved for refractory thrombocytopenia with life
      threatening hemorrhage in acute ITP or after recurrent severe thrombocytopenia in
      chronic ITP. Other immunomodulatory therapies are also discussed.

PMID- 9523748
TI  - Management of chronic immune thrombocytopenic purpura in children and adults.
AB  - Chronic immune thrombocytopenic purpura (ITP) is characterized by macrophage
      destruction of platelets, primarily in the spleen, and occurs in both adults and
      children. Historically, splenectomy is often required, especially in adults with
      chronic ITP; however, several medical options have been used successfully prior
      to splenectomy or when this procedure has either failed or been refused by the
      patient. These include corticosteroids, intravenous immunoglobulin (IVIg),
      intravenous anti-D, danazol, vinca alkaloids, and other immunosuppressive agents
      such as azathioprine and cyclophosphamide. Platelet transfusions have been used
      in emergency situations. Several therapies that have been reported, but that are
      rarely used in chronic ITP, include cyclosporine A, interferon-alpha (IFN-alpha),
      plasma exchange, staphylococcal protein A immunoadsorption, combination
      chemotherapy, dapsone, ascorbic acid, and colchicine. Each of these approaches to
      treatment of chronic ITP are discussed.

PMID- 9523749
TI  - Clinical experience with anti-D in the treatment of idiopathic thrombocytopenic
      purpura.
AB  - Idiopathic thrombocytopenic purpura (ITP), an autoimmune disease of children and
      adults, is characterized by low platelet counts and bleeding through mucous
      membranes. While not uncommon among otherwise healthy adults and children, ITP is
      a frequent complication of human immunodeficiency virus (HIV) infection. Anti-D
      is a gamma globulin (IgG) fraction containing a high proportion of antibodies to
      the Rh0 (D) antigen of the red blood cells. Clinical studies over the past 10
      years have shown intravenous anti-D to be a safe and effective treatment for Rh
      positive, nonsplenectomized patients with ITP (classic or HIV-related). While it
      is unlikely that anti-D is a curative treatment for ITP, repeated infusions can
      be used to maintain the platelet count at a level sufficient to provide adequate
      hemostasis (>30,000/microL) and may enable patients to postpone or even avoid
      splenectomy.

PMID- 9523750
TI  - Idiopathic thrombocytopenia purpura: Treatment patterns and an analysis of cost
      associated with intravenous immunoglobulin and anti-D therapy.
AB  - A retrospective study was conducted to determine treatment patterns for
      idiopathic thrombocytopenia purpura (ITP) across the US and to determine the cost
      of its treatment with high-dose intravenous immunoglobulin (IVIg) and anti-D
      therapy. Information on the incidence, treatment patterns, hospital care, and
      costs for ITP was derived from three data bases and supplemented by in-depth case
      studies from five hospital centers in the US. Data collection forms were
      developed to collect data on treatment patterns and costs at the five hospital
      centers. Treatment patterns were analyzed and used to model the comparative costs
      of IVIg and anti-D therapy. Cost estimations were based on a process and cost
      finding analysis reflecting current practice patterns for the use of IVIg and
      anti-D therapy in an outpatient clinic. The incidence of ITP was estimated at 65
      per 10,000 in human immunodeficiency virus (HIV)-positive individuals and 1.5 per
      10,000 in HIV-negative individuals. Hospital discharge data from all 1991 and
      1992 hospital discharges in Maryland revealed that both Medicare patients and
      patients who had other payment options spent less time in hospital compared to
      Medicaid patients. The limited case study data indicate that anti-D therapy
      increased platelet counts to greater than 25,000/microL in 82% of evaluable
      episodes and that IVIg-treated patients reached 25,000/microL in 48% of treated
      episodes. The estimated cost per treated episode of ITP was $4,269 for IVIg and
      $2,716 for anti-D therapy, reflecting a cost savings of $1,553 per episode. This
      retrospective study has shown that the use of anti-D therapy is associated with
      lower costs compared with IVIg treatment in patients with ITP. The shorter
      infusion time required for anti-D therapy may also contribute to a better quality
      of life for patients.

PMID- 9523752
TI  - 7Li and 23Na NMR studies of transmembrane cation transport mediated by ionophore
      lasalocid A.
AB  - Ion transport across phospholipid vesicles was studied by 7Li and 23Na-NMR using
      an aqueous anionic paramagnetic shift reagent, dysprosium nitrilotriacetate
      [Dy(NTA)2](3-), mediated by ionophores, lasalocid A and A23187. The intra- and
      extracellular 7Li and 23Na-NMR signals were well separated (20 Hz) at mM
      concentration of the shift reagent. The observed data on the rate constant for
      lithium transport across DPPC vesicles at various concentrations of the
      ionophores indicated that lasalocid A is a more efficient carrier for lithium ion
      compared with the sodium ion transport by this ionophore, while A23187 was not
      specific to either of the ions (Li or Na).

PMID- 9523751
TI  - Applications of the Mitsunobu reaction in peptide chemistry.
AB  - The Mitsunobu reaction--the nucleophilic substitution of an alcoholic hydroxyl
      group mediated by the redox system trialkylphosphine/dialkyl azodicarobxylate--is
      widely used in the chemistry of biologically active compounds. The paper deals
      with applications of the Mitsunobu reaction in amino acid and peptide chemistry.
      The process provides easy access to many unnatural amino acids and derivatives.
      Since the reaction occurs with complete inversion of the configuration at the
      carbinol chiral centre, it can be used for the synthesis of diastereoisomers of
      hydroxy- and tioprolines. Cyclization of beta-hydroxy amino acid containing
      peptides under Mitsunobu reaction conditions leads to a constrained peptide that
      mimics the stabilizing reverse turn secondary structure.

PMID- 9523753
TI  - Conformational behaviour of C(alpha,alpha)-diphenylglycine: folded vs. extended
      structures in DphiG-containing tripeptides.
AB  - The crystal structures of three fully protected tripeptides containing the Dphi g
      residue (C[alpha,alpha]-diphenylglycine) in the central position are reported,
      namely Z-Gly-Dphi g-Gly-OMe (a), Z-Gly-Dphi g-Aib-OMe (b) and Z-Aib-Dphi g-Aib
      OMe (c). The molecular conformations are quite unusual because the Dphi g residue
      adopts a folded conformation in the 3(10)-helical region when the following
      residue adopts a folded conformation of opposite handedness (peptides b and c).
      In contrast, the Dphi g residue adopts the more frequently observed fully
      extended conformation when the following residue adopts a semi-extended
      conformation (peptide a). These findings are in agreement with the theoretical
      calculations on Ac-Dphi g-Aib-NHCH3 and Ac-Aib-Dphi g-NHCH3 also reported in this
      work.

PMID- 9523755
TI  - Alpha-hydroxymethylserine as a peptide building block: synthetic and structural
      aspects.
AB  - A synthetic methodology has been developed for peptide bond formation with alpha
      hydroxmethylserine as the carboxyl or amino component and also for the
      preparation of homo-sequences. The key intermediate, O,O-protected alpha
      hydroxymethylserine in the form of an isopropylidene derivative, is easily
      accessible and represents the first example of a heterocyclic C(alpha,alpha)
      disubstituted amino acid containing an 1,3-dioxane ring. The use of this
      intermediate facilitates protection of the sterically hindered amino and carboxyl
      groups and is advantageous for the coupling and deprotection steps. X-ray
      structure determination of Z-HmS(Ipr)-Ala-OMe revealed that the two
      crystallographically independent molecules present in the asymmetric unit adopt
      an S-shaped conformation. In the one molecule the achiral HmS(Ipr) residue has
      the torsion angle values (phi = 61.4 degrees, psi, = 40.8 degrees) in the left
      handed helical region of the Ramachandran map, while in the second molecule the
      negative torsion angles (phi = -60.1 degrees, psi = -44.4 degrees) are associated
      with the right-handed helix.

PMID- 9523754
TI  - Linear and cyclic peptides as substrates for Lyn tyrosine kinase.
AB  - Two Tyr residues are supposed to play a crucial role in the regulation of protein
      tyrosine kinases of the Src family. Autophosphorylation of Src Tyr416 correlates
      with enzyme activation, while phosphorylation of C-terminal Tyr527 by Csk gives
      rise to inactive forms of Src kinases. It has previously been demonstrated that
      the Src-like tyrosine kinase expressed by the oncogene lyn displays a
      particularly high affinity (Km 20 microm) toward the dimeric linear and cyclic
      derivatives of the heptapeptide H-Glu-Asp-Asn-Glu-Tyr-Thr-Ala-OH which reproduces
      the main autophosphorylation site of most of the Src enzymes. Under the
      experimental conditions used only one Tyr residue of the dimeric sequence can be
      phosphorylated [P. Ruzza, A. Calderan, B.Filippi, B. Biondi, A. Donella Deana, L.
      Cesaro, L. A. Pinna & G. Borin (1995) Int. J. Peptide Protein Res. 45, 529-539].
      The present study addresses the problem of the efficiency displayed by Lyn
      towards the two Tyr residues located at positions 5 and 12 of the dimeric
      peptide. To this purpose, two tetradecapeptides were synthesized by the classical
      solution method, each containing one of the two Tyr residues alternatively
      replaced by Phe, and the corresponding univocal cyclic form. A possible
      correlation between the different structural properties induced by the
      modifications of the native sequence and the ability of the peptides to act as
      Lyn substrates was noted. The kinetic data obtained indicate that Lyn
      phosphorylates the residues located at different positions in the two linear
      analogues differently. In particular, while the Tyr5, Phe12 derivative presents a
      Km value similar to those obtained for the dimeric linear and cyclic unmodified
      analogues, the Km value of the Phe5, Tyr12 derivative is two-fold higher than
      those found for the above-mentioned peptides. Moreover, as previously reported
      for the linear and cyclic dimeric forms of the native sequence, in the mono
      tyrosine containing series of dimers the still conformationally flexible cyclic
      derivative shows a phosphorylation efficiency two-fold higher than those found
      for the linear derivatives.

PMID- 9523756
TI  - Conformational investigations on glycosylated threonine-oligopeptides of
      increasing chain length.
AB  - Stepwise solution syntheses are described of the homo-oligomers Z-(Thr)n-NHCH3
      (n=1-4, I1-4), Z-?[Gal(Ac)4beta]Thr?n-NHCH3(n=1-5, II1-5) and Z-[(Galbeta)Thr]n
      NHCH3 (n=1-5, III1-5). Members of the III1-5 series were obtained by de
      acetylation of the corresponding oligomers of the II1-5 series. The
      conformational preferences of the terminally protected homo-peptides of the three
      series were investigated by FT-IR absorption spectroscopy both in the solid state
      and in CDCl3 solution, at various concentrations. Proton NMR measurements in
      CDCl3 and in DMSO-d6 were also carried out and the effect of temperature
      variation on the chemical shifts of amide protons was determined in DMSO-d6
      (range 298-335 K) and in CDCl3 (range 298-320K). CD spectra were recorded in
      water and in TFE. Solubility problems prevented measurements in CDCl3 solution
      for Z-(Thr)4-NHCH3 and for the entire III1-5 series. The existence of unordered
      structures in the carbohydrate-free oligomers and of more or less extended,
      organized structures in the glycosylated derivatives is indicated by the NMR and
      IR measurements. The sugar moieties apparently show a structure-inducing effect
      on the peptide chain.

PMID- 9523757
TI  - Chemoselectively addressable HCan building blocks in peptide synthesis: L
      homocanaline derivatives.
AB  - (S-2-amino-5-(aminooxy)pentanoic acid (L-homocanaline, HCan), a structural
      analogue of lysine, contains a reactive alkyloxyamine side chain and is therefore
      considered to react chemoselectively with carbonyl compounds by forming a
      kinetically stable oxime bond. The chemical synthesis of L-homocanaline starting
      from protected glutamic acid derivatives is described. Two orthogonally protected
      homocanaline derivatives were synthesized and their use in standard SPPS
      procedures was exemplified for the synthesis of a chemoselectively addressable
      cyclic peptide for use in TASP design. Moreover, the wide range of applications
      of this unique building block was demonstrated for the chemoselective ligation of
      an unprotected disaccharide to a HCan containing model peptide resulting in a
      chimeric glycopeptide structure.

PMID- 9523758
TI  - Structural evolution in boron nitrides during the hexagonal-cubic phase
      transition under high pressure at high temperature.
AB  - Structural evolution during the phase transition from h (hexagonal)- to c (cubic)
      boron nitrides (BN) under high pressure (6.5-7.7 GPa) at high temperature (1,700
      2,150 degrees C) was examined by using high-resolution transmission electron
      microscopy (HRTEM) and electron energy loss spectroscopy (EELS). At the initial
      stage of the evolution, some starting h-BN plates were strongly folded, while
      others were slightly bent. As a result, a strong texture was formed. HRTEM
      revealed that the interplanar distance between sp2 sheets became slightly
      shortened and they were slightly sheared to each other during the folding and
      bending. As a result, m (monoclinic)-BN was formed near the folding plane with
      lattice parameters; a = 0.433 nm, b = 0.250 nm, c = 0.32-0.33 nm, and beta = 90
      92 degrees. In a succeeding stage, the value of beta increased to 92-95 degrees.
      c-BN grains appeared with nano-scale twins and sometimes partly included wurtzite
      type BN. They started to grow with secondary twins at higher temperature. EELS
      analysis revealed that the band structure of sp2 sheets changed during the
      transition from h-BN to m-BN; the density of state for the pi* bond became
      prominently high in m-BN as compared to that in h-BN.

PMID- 9523759
TI  - High-voltage high-resolution electron microscopy study of alkaline-earth copper
      oxides.
AB  - Two families of alkaline-earth copper oxides are studied by using high-voltage
      high-resolution electron microscopy. One is Sr(n-1) Cu(n)O(2n-1) (n = 2, 3), the
      so-called spin-ladder compounds, and the other is ACuO2 (A = Ca-Sr) crystallizing
      in the infinite-layer structure, which is a parent structure for all copper oxide
      superconductors. It is demonstrated in the former compounds that oxygen columns
      as well as metal columns are directly imaged in a "structure" image. Moreover,
      twin-related lattice defects, which can be the origin of free Cu2+ spins observed
      previously in magnetic measurements, have been detected in SrCu2O3. An
      interesting irradiation effect under a 1,000-kV electron beam has been observed
      in the infinite-layer compound: An unusual structural phase transformation to a
      NaCl-type lattice is induced, accompanied by the formation of nm-size twin
      domains.

PMID- 9523760
TI  - Ultimate observation of tungsten atoms and clusters adsorbed on single
      crystalline MgO films.
AB  - Tungsten single atoms and clusters composed of four and five atoms deposited on
      MgO (001) thin films were observed by high-resolution transmission electron
      microscopy at R.T. The observation was realized by optimizing the thickness of
      the MgO films and by using special imaging techniques such as an off-Bragg HREM
      method. The multislice simulation for the interpretation of the image contrast
      showed a possibility of discrimination of the atomic configuration of clusters,
      such as "b.c.c.," "on-top," or "f.c.c." type clusters, from details of the image
      contrast. The image intensity at the center of the clusters with the b.c.c.
      configuration was evidently smaller than that of the clusters with the f.c.c.
      configuration. The reason for the difference was clarified through the multislice
      image simulation, suggesting that the lattice mismatch between the clusters and
      the MgO lattice was a key factor in determining the intensity of the center of
      the clusters.

PMID- 9523761
TI  - New stacking variant of Laves phase found in (Ti0.95 V0.05) Co2 alloy.
AB  - Microstructures of the Laves phase alloy, (Ti0.95 V0.05) Co2, were studied by
      high resolution electron microscopy and electron diffraction. In this alloy
      system, coexistence of several kinds of layered structures was observed. Among
      these structures, a new stacking variant was found and was analyzed to be
      ABCAB'A'C'BCA'C'B'. This structure belongs to the trigonal system of the space
      group P3m1 (no. 164). The lattice parameters presented in the hexagonal system
      are a = 0.4727 +/- 0.0009 nm and c = 4.628 +/- 0.008 nm. This structure is called
      12T in the Ramsdell notation and 4323 in the Zhdanov symbol, and is classified
      into hP3m1-(6i)5(3f)(3e)(2d)12(2c)6 using the Wyckoff notation.

PMID- 9523762
TI  - Study of amorphous alloy structures with medium range atomic ordering.
AB  - Structures with atomic medium range order (MRO) extending as small as
      approximately 2 nm in amorphous alloys can be observed under suitable defocus
      conditions as clear lattice fringe images by means of axial-beam high-resolution
      electron microscopy (HREM). In this article, our studies of local structure
      observation in some metal-metalloid amorphous alloys with the "selected-defocus
      method" are introduced. Also introduced are an HREM image simulation study of
      amorphous alloy structures and a nano-probe (1-1.5 nm) electron diffraction
      analysis of MRO structure. A multislice image simulation study for suitable
      structure models (1) with a random atomic distribution, (2) with MRO regions
      having different sizes, distributions, and specimen thicknesses, is a necessary
      step to verify the MRO observation in amorphous alloys. It was demonstrated that
      not only HREM information but also nano-diffraction information are necessary in
      order to understand local structures of amorphous alloys.

PMID- 9523763
TI  - Structure analysis of defects in nanometer space inside a crystal: creation and
      agglomeration of point defects in Si and Ge revealed by high-resolution electron
      microscopy.
AB  - Recent structural studies of point-defect-agglomerates in Si and Ge by high
      resolution transmission electron microscopy (HRTEM) are compiled along with some
      new results. After examining the wave nature of incident electrons on defect
      formation during HRTEM observation and the correlated recombination of point
      defects under electron irradiation, we show that HRTEM is the unique means to
      analyze the atomic structure of small agglomerates of point defects, nanometer in
      size, inside a crystal. Emphasis is placed on the extension of studies made
      possible only by the elaborate and crucial structure determination by HRTEM: the
      mechanism of agglomeration at the atomic level, the extraction of novel unit
      structures of point defects, and the electronic structure of the agglomerate.
      Some examples on the subjects are demonstrated in cases of the [113] and [001]
      defects. The effect of specimen surfaces on structure determination is also
      discussed. Finally, a development of TEM technique with in-situ optical
      spectroscopy is described, which is utilized to pursue interaction of point
      defects under electron irradiation and thus may reinforce HRTEM experiments.

PMID- 9523764
TI  - Characterization of microstructural morphology of austempered ductile iron by
      electron microscopy.
AB  - Mechanical properties of austempered ductile iron (ADI) are mainly controlled by
      its unique microstructure. The objectives of this paper are to characterize the
      microstructural morphology and the phase distribution of ADI using scanning
      electron microscopy (SEM) and transmission electron microscopy (TEM) and to
      determine the mechanism of strengthening and toughening of ADI. The experimental
      results show that, in the microstructure of ADI composing of upper bainite,
      retained austenite, graphitic nodule, and a small amount of martensite, the upper
      bainite is composed of sub-units of ferrite in the shape of "wheat ears" on which
      the "wheat grains" grow at an angle of about 60 degrees to the long axis of the
      "wheat ears." The retained austenite is connected with each other in the shape of
      a continuous net. The wheat-ear like bainite with a homogeneous distribution in
      the continuous austenite net plays an important role to the strengthening and
      toughening of ADI. The metastable austenite appears in the shape of a large plate
      in which the martensite is preferentially formed. The appearance of martensite
      can be suppressed at the time when retained austenite remains stable, which is of
      benefit to the continuity and homogeneity of austenite net.

PMID- 9523765
TI  - Quantitative evaluation of opioid withdrawal signs in rats repeatedly treated
      with morphine and injected with naloxone, in the absence or presence of the
      antiabstinence agent clonidine.
AB  - An opioid withdrawal syndrome was induced in rats by repeated morphine
      administration and final naloxone injection. The withdrawal causes alteration of
      several physiological signs. The aim of the study was to describe a quantitative
      opioid abstinence syndrome to validate the methodology by utilizing clonidine, a
      well-known antiwithdrawal agent, and propose the procedure for the screening of
      antiabstinence drugs. In particular, rats were treated with saline, morphine,
      naloxone, morphine and naloxone and four doses of clonidine (0, 0.04, 0.1, and
      0.25 mg/kg orally). In rats repeatedly exposed to morphine and then injected with
      naloxone, signs like excretion of feces and urine, salivation, behavioral jumping
      and wet dog shakes, rectal temperature, and pain threshold have been observed.
      Consequently, the objective symptoms observed in morphine plus naloxone-treated
      animals have been taken as markers of opioid withdrawal. These factors have been
      quantitatively measured and grouped to form a standardized procedure of opioid
      abstinence syndrome. In addition, it is possible to observe that the
      antiabstinence drug clonidine exerted effects on modified physiological signs
      appearing in morphine-dependent rats treated with naloxone, like fecal excretion,
      levels of rectal temperature, latency times, salivation as well as jumping
      behavior. The effects exerted by clonidine in this procedure and in other methods
      are compared and appear to be similar. In addition, comparative observations
      referring to both the previous methods and the present procedure related to the
      type of signs studied, the modality of evaluation, and suppressive activity
      exerted by the antiwithdrawal agent, clonidine, are performed: the greater
      accuracy of the proposed method becomes apparent. Thus, this experimental model,
      validated by the antiabstinence agent clonidine, is proposed as a useful screen
      for drugs affecting opioid withdrawal syndrome.

PMID- 9523766
TI  - Rapid generation of homologous internal standards and evaluation of data for
      quantitation of messenger RNA by competitive polymerase chain reaction.
AB  - Sensitive and quantitative measurement of messenger RNA (mRNA) is important for
      accurate assessment of gene expression. Conventional methods of mRNA measurement
      frequently lack the sensitivity required to detect mRNA expressed at low level,
      such as mRNA encoding receptors and intracellar signaling molecules. Thus, the
      extremely sensitive RT-PCR has become the method of choice for examination of
      gene expression. However, quantitation of mRNA by PCR is difficult because small
      variations in amplification efficiencies among sample tubes can lead to
      substantial differences in product yield, thereby rendering direct comparisons
      between samples invalid. Development of protocols for quantitative RT-PCR has
      relied on internal standards to monitor the efficiency of the RT-PCR in different
      reaction tubes. Technically, the two most serious limitations to routine
      successful application of competitive quantitative PCR is ready access to
      competitive internal standards and efficient methods for accurate quantitative
      analysis of the data. In the present manuscript, application and validation of a
      simple approach to generate homologous internal competitive standards and to
      quantitate data for rapid, accurate determination of the expression level of
      genes by quantitative PCR is described. Generation of the competitive standard
      from a previously amplified PCR product by the methods described requires only
      one additional primer pair, and an additional two-step reaction; it can be
      completed in 1-2 days. Analyzing the results of the competitive PCR reaction via
      phosphoimager analysis provides a simple, rapid method for accurate quantitation
      of results. Data presented here clearly illustrate that the methods described
      have been successfully applied, and that they should have wide application for
      competitive quantitative PCR analysis of gene expression.

PMID- 9523767
TI  - Hepatocyte primary culture bioassay: a simplified tool to assess the initiation
      of the liver regeneration cascade.
AB  - The objective was to develop and optimize a hepatocyte primary culture bioassay
      to detect proliferative factors (PF) in the serum or plasma of partially
      hepatectomized (PHX) rats to serve as a tool to assess the initiation of the
      liver regeneration cascade. The bioassay detects PF by measuring hepatocyte
      proliferation through directly counting increases in viable cell number over the
      culture period using a hemocytometer. Hepatocytes were obtained using a two-step
      collagenase perfusion procedure. The purified hepatocytes (>80% viability, >95%
      parenchymal cells) were seeded into 6-well culture plates and allowed to attach
      overnight. The unattached cells were washed out, and the starting cell count was
      determined from three randomly selected wells after trypsin digestion. Sera from
      2/3 PHX rats at 1-6 h postPHX was added to the culture. With a medium change at
      24 h, the final cell counting was performed at 48 h. The net cell proliferation
      was expressed as the difference between the counts at 48 h and starting h. The
      optimized assay conditions could detect an increase of PF in PHX rat serum
      between 1 and 4 h after PHX (peaking at 4 h). The bioassay showed both a
      qualitative and quantitative sensitivity to distinguish between the PF levels in
      1/3 and 2/3 PHX rats.

PMID- 9523768
TI  - Redox potential measurements of plasma in patients undergoing coronary artery
      bypass graft and its clinical significance.
AB  - The apparent redox potentials (Em) of plasma as a marker of oxidant injury during
      coronary artery bypass graft (CABG) is determined, and their clinical
      significance is discussed. We measured plasma Em of normal volunteers (n = 20)
      and samples drawn at different time points from patients undergoing elective CABG
      (n = 60) directly and by adding 5 microl (20 mM) oxidants or reductants with
      known redox potential to plasma (95 microl), using a micro Pt/AgCl combination
      redox electrode. The Em value stays elevated up to 30 min during the surgery,
      after the administration of protamine it came down toward a more reduced state.
      Similar changes are seen with the lactate pyruvate ratio. Smaller changes of Em
      than normal are observed in plasma samples from patients treated with Aprotinin
      (antiprotease), Carmeda (heparin-coated) circuit and aspirin reflecting their
      protective effect. Redox potential (Em) measurements appear to be effective and
      useful in monitoring redox shifts wherever oxidative stress needs to be
      monitored.

PMID- 9523770
TI  - Isolation of liver nuclei that retain functional trans-membrane transport.
AB  - We have developed a method for the rapid isolation of hepatocyte nuclei, which
      employs gentle homogenization and centrifugation conditions, and involves minimal
      processing time. The purified nuclei were morphologically unaltered when observed
      by light and electron microscopy. No significant contamination from cytoplasm or
      mitochondria was detected when assessed by marker enzymes. Membrane transport
      function, measured as ATP-dependent calcium uptake, was intact. This isolation
      method was devised to be applicable to studies that involve measurement of uptake
      and active transport of a variety of substances by the cell nucleus.

PMID- 9523769
TI  - The influence of restraint on blood pressure in the rat.
AB  - We examined the influence of procedures used in blood pressure measurement on
      blood pressure and the effects of antihypertensive agents. Subjects were
      spontaneously hypertensive rats (SHR) and their Wistar/Kyoto (WKY) controls.
      Blood pressure was recorded by telemetry. Twenty-four h baseline pressure were
      measured, and the effect of minor handling on blood pressure and heart rate was
      examined. The influence of restraint such as is used for tail-cuff blood
      pressures was examined. The effects of three different antihypertensive drugs was
      also examined in the SHR. In the home-cage environment, the SHRs showed higher
      systolic blood pressures, but had similar hypertensive responses to minor
      handling as the WKYs. Both strains had elevated heart rate and blood pressure
      when restrained in the manner used for tail-cuff readings. The antihypertensive
      effects of captopril and losartan in the SHR were unchanged when the animals were
      restrained but the hypotensive effect of hydralazine was greater. These results
      confirm that significant changes in heart rate and blood pressure can occur as a
      result of the minor procedures frequently used in blood pressure recording in
      both SHR and WKY rats. This suggests that telemetry may have significant
      advantages as a method for continuous blood pressure monitoring. The
      pharmacological profile of antihypertensive drugs may well be different in
      animals where telemetry is employed and are not subject to the stresses involved
      in previous methods of monitoring blood pressure.

PMID- 9523771
TI  - Development and pharmacological characterization of a modified procedure for the
      measurement of carbonic anhydrase activity.
AB  - Carbonic anhydrases (CAs) are a family of zinc metalloenzymes of molecular mass
      30-60 kDa; seven different isoenzymes belong to this family (Okuyama et al.,
      1992, Proc Natl Acad Sci USA 89:1315-1319). They may be broadly recognized
      according to the efficiency with which they catalyze the reversible
      interconversion of CO2 and HCO3-, and they differ in physicochemical properties,
      in sensitivity to various inhibitors and in their subcellular localization;
      cytoplasmic (CA I, CA II, CA III, and CA VII), cell-surface membrane (CA IV), and
      mitochondrial (CA V) and secretory (CA VI) isoenzymes have been described.
      Several methods are reported in the literature for the measure of CA enzymatic
      activity; they may be broadly divided into two categories: those based on the
      measure of pH variation (pH-stat and colorimetric assays) (Wu et al., 1993, J
      Ocular Pharm 9:97-108; Maren, 1991, Molec Pharmacol 41:419-426) and the ones in
      which CO2 production is measured through pCO2 sensors (Botre and Botre, 1990,
      Anal Biochem 185:254-264).

PMID- 9523772
TI  - The emerging science of functional assessment: our tool for outcomes analysis.

PMID- 9523773
TI  - Diagnostic coding and medical rehabilitation length of stay: their relationship.
AB  - OBJECTIVE: To determine if diagnostic information provided in the form of
      International Classification of Diseases, 9th Revision, Clinical Modification
      (ICD-9-CM) codes improves rehabilitation length of stay (LOS) prediction when
      used in combination with the Functional Independence Measure-Function Related
      Groups (FIM-FRGs) classification system. DESIGN: Various models characterizing
      diagnostic information using ICD-9-CM codes were created that included individual
      ICD-9-CM codes and groupings of those codes by organ or etiology involved. Each
      method was evaluated using linear regression with the natural logarithm of LOS as
      the dependent variable. Separate validation data sets were held back to quantify
      the incremental effect of diagnosis when combined with the FIM-FRG classification
      system. SETTING: Records from 252 rehabilitation facilities and hospital units
      across the nation. PATIENTS: Analyses were undertaken using 82,646 records from
      patients discharged in 1992. RESULTS: The addition of ICD-9-CM diagnostic
      information to the FIM-FRG classification system increased the variance explained
      by a maximum of 1.9%, from 31.5% to 33.4%. CONCLUSIONS: Refinement of the FIM
      FRGs to include ICD-9-CM diagnoses does not appear warranted on the basis of the
      small increase in the percentage of explained variance in LOS. We believe the
      lack of improved prediction with the addition of ICD-9-CM codes relates primarily
      to incomplete coding practices and to the effect of patients' diagnoses being
      absorbed in variables as already expressed by the FIM-FRG system. Although ICD-9
      CM codes, overall, did not greatly improve LOS prediction, they appeared to have
      some impact in certain impairment categories.

PMID- 9523774
TI  - A randomized controlled evaluation of low-intensity laser therapy: plantar
      fasciitis.
AB  - OBJECTIVE: To determine whether low-intensity laser irradiation, a widespread but
      controversial physical therapy agent, is an effective treatment of plantar
      fasciitis. DESIGN: A randomized, double-blinded, placebo-controlled clinical
      study. SETTING: A sports medicine clinic. SUBJECTS: Thirty-two otherwise healthy
      individuals with plantar fasciitis of more than 1 month's duration. INTERVENTION:
      Dummy or active irradiation with a 30 mW .83 microm GaAlAs continuous-wave
      infrared (IR) diode laser three times a week for 4 weeks. MEASUREMENTS: Morning
      pain, pain with toe walking, tenderness to palpation, windlass test response,
      medication consumption, and orthotic use were evaluated immediately before the
      study, as well as at the midpoint and end of treatment. Subjects were also
      evaluated at a follow-up 1 month after their last treatment. RESULTS: No
      significant differences were found between the groups in any of the outcome
      measures either during treatment or at the 1-month follow-up. Treatment, however,
      was well tolerated and side effects were minimal. CONCLUSIONS: Low-intensity IR
      laser therapy appears safe but, at least within the parameters of this study, is
      not beneficial in the treatment of plantar fasciitis.

PMID- 9523775
TI  - Vesicourethral dysfunction and urodynamic findings in multiple sclerosis: a study
      of 149 cases.
AB  - OBJECTIVE: Vesicourethral dysfunction is common in people with multiple sclerosis
      and results in significant impairment. We studied the clinical and urodynamic
      findings in such patients to define risk factors for incontinence and upper
      urinary tract infections. DESIGN AND SETTING: A cohort study of 149 patients with
      multiple sclerosis and urinary symptoms seen in our urodynamic laboratory.
      INTERVENTION: A complete urodynamic study of each patient with urethrocystometry
      and continuous recording of the urethral sphincter electromyography and
      assessment of postvoid residual. RESULTS: Detrusor hyperreflexia and sphincter
      dyssynergia were the main dysfunctions. No significant relation between clinical
      features and urodynamic patterns was found. Women with low maximal urethral
      pressure were particularly prone to incontinence, which occurred in 69% of the
      patients. Pyelonephritis was associated with a postvoiding residual urine of >
      30% of the functional detrusor capacity, and was found more often in the male
      population. CONCLUSION: Urodynamic assessment of bladder function is critical to
      direct therapy for urinary complaints in people with multiple sclerosis.

PMID- 9523776
TI  - Types of spiritual well-being among persons with chronic illness: their relation
      to various forms of quality of life.
AB  - OBJECTIVES: Derive a spiritual well-being classification and thereby enhance
      understanding of the relation between spiritual well-being, quality of life
      (QOL), and health among persons with chronic illness or disability. DESIGN:
      Cluster analyses were performed to develop a spiritual well-being classification.
      Analysis of variance was used to compare cluster groups on various dimensions of
      QOL. SETTING: Part of a larger QOL study conducted at a midwestern medical
      center. PATIENTS: A convenience sample of 216 inpatients: amputation (n = 74),
      postpolio (n = 37), spinal cord injury (n = 34), breast cancer (n = 36), and
      prostate cancer (n = 35). Minors were excluded from the study. MAIN OUTCOME
      MEASURES: Spiritual Well-Being Scale (SWBS), Functional Assessment of Cancer
      Therapy (FACT), Functional Living Index-Cancer (FLIC), Sickness Impact Profile
      (SIP), Medical Outcome Survey-Short Form (SF-36), and the Satisfaction With Life
      Scale (SWLS). RESULTS: Three types of spiritual well-being were identified:
      religious (n = 146), existential (n = 37), and nonspiritual (n = 30). Significant
      cluster differences (p < .03 to p < .001) were observed across all QOL domains
      and life satisfaction. Compared with the other cluster groups, the nonspiritual
      group reported significantly lower levels of QOL and life satisfaction and the
      highest proportion of health status change with respect to both improvement and
      decline in health. CONCLUSIONS: Three types of spiritual well-being were
      empirically identified in this sample. Subtypes differed significantly with
      respect to various aspects of QOL. Further research is needed to validate this
      classification and to determine if type of spiritual well-being has a causal
      effect on treatment outcome or on the recovery process.

PMID- 9523777
TI  - Skin response to repetitive mechanical stress: a new experimental model in pig.
AB  - OBJECTIVES: To develop a new animal model for investigating the relations between
      interface stresses at the skin, adaptation, and breakdown. There were two
      hypotheses. (1) In skin subjected to varying types of repetitive mechanical
      stress, the tissue response depends on the direction and magnitude of the load.
      As the shear stress increases, tissue breakdown occurs earlier. (2) In skin
      subjected to repetitive mechanical stress of longer duration, there will be
      evidence of tissue adaptation. DESIGN: Multiple case control, single-blind.
      INTERVENTIONS: Varying combinations of normal and shear mechanical loads are
      applied to pig's skin for short durations (breakdown studies) or longer durations
      (adaptation studies). MAIN OUTCOME MEASURES: Gross evidence of breakdown (visual
      inspection of skin) and microscopic changes (eg, histologic features of
      breakdown; thickness of epidermis and dermis; the length and shape of the
      basement membrane; concentration of inflammatory cells, mast cells, and
      fibroblasts; and quantity of elastin fibers). RESULTS: The instrumentation was
      reliable and a significant improvement over past models in that shear forces were
      delivered and measured in a controlled manner. The animal model and tissue
      methodology provided consistent results, and it was found that skin breakdown
      occurred earlier as shear forces were increased. Evidence of tissue adaptation
      occurred in the long-term experiments, although corresponding morphologic changes
      have been difficult to elucidate. CONCLUSIONS: To address the problem of skin
      breakdown, new animal models are strongly needed to better understand basic
      biologic processes related to pressure ulcer development.

PMID- 9523778
TI  - Sensory, motor, and pain thresholds for stimulation with medium frequency
      alternating current.
AB  - OBJECTIVES: To investigate the effect of frequency of alternating current on the
      sensory, motor, and pain thresholds in normal subjects, and to establish the
      optimal frequency for motor stimulation with minimal subject discomfort. DESIGN:
      A repeated measures design using two groups of 11 subjects. SETTING: A laboratory
      setting was used. PARTICIPANTS: Participants were volunteers who met the
      inclusion criteria. INTERVENTIONS: Alternating current with 20 different carrier
      frequencies between 1 and 35 kHz, all modulated at 50 Hz, was applied to each
      subject on two separate occasions. For half the subjects, the frequency was
      increased or decreased sequentially (reversed on second occasion), and for the
      other half, it was applied in a different random order on each occasion. MAIN
      OUTCOME MEASURES: The voltage at the sensory threshold was recorded for each
      applied frequency. This was subsequently repeated for motor and pain thresholds.
      RESULTS: Sensory, motor, and pain thresholds decreased with increasing frequency
      between 1 kHz and approximately 10 kHz. Above 10 kHz, the thresholds increased.
      The ratio pain threshold/sensory threshold increased systematically with
      increasing frequency over the range examined. By contrast, the ratio pain
      threshold/motor threshold showed a distinct maximum at a frequency of 10 kHz.
      Marked accommodation to motor and pain fiber stimulation was observed.
      CONCLUSIONS: For comfortable sensory stimulation, a high frequency of alternating
      current is preferable. Discrimination between pain and motor stimulation is
      maximal at a frequency of approximately 10 kHz. This suggests that the optimal
      frequency for comfortable motor stimulation, one that is least likely to elicit
      pain fiber stimulation, is close to 10 kHz.

PMID- 9523780
TI  - The predictive value of provocative sacroiliac joint stress maneuvers in the
      diagnosis of sacroiliac joint syndrome.
AB  - OBJECTIVE: To determine the clinical validity of provocative sacroiliac joint
      (SIJ) maneuvers in making the diagnosis of sacroiliac joint syndrome (SIJS).
      DESIGN: Prospective constructive cohort study using sacroiliac joint block (SIJB)
      as the diagnostic gold standard. SETTING: Tertiary care center. PATIENTS:
      Consecutive patients describing low back pain including the region of the sacral
      sulcus. Physical examination revealed a positive response to three provocative
      SIJ maneuvers, two of which had to be Patrick's test and pain with palpation over
      the ipsilateral sacral sulcus. INTERVENTIONS: All subjects underwent
      fluoroscopically guided SIJB. MAIN OUTCOME MEASURES: Response to SIJB was
      assessed with visual analog scale (VAS) ratings before and after the block. A
      reduction of the VAS rating by at least 80% was considered a positive response to
      SIJB. RESULTS: Fifty consecutive patients met our criteria and underwent SIJB.
      Thirty patients had positive response to SIJB, making up the positive SIJS group.
      Twenty patients had less than 80% pain reduction with SIJB and thus comprised the
      negative SIJS group. The positive predictive value of provocative SIJ maneuvers
      in determining the presence of SIJS is therefore 60%. CONCLUSIONS: Our results do
      not support the use of provocative SIJ maneuvers to confirm a diagnosis of SIJS.
      Rather, these physical examination techniques can, at best, enter SIJS into the
      differential diagnosis.

PMID- 9523779
TI  - Incidence, acute care length of stay, and discharge to rehabilitation of
      traumatic amputee patients: an epidemiologic study.
AB  - OBJECTIVE: To examine patterns of trauma-related amputations over time by age and
      gender of the patient and by level and type of amputation, and to explore factors
      affecting acute care length of stay and discharge to inpatient rehabilitation.
      DESIGN: Population-based hospital discharge data for Maryland from 1979 through
      1993. PARTICIPANTS: Patients (N = 6,069) discharged with either (1) a principal
      or secondary diagnosis of a trauma-related amputation to the upper or lower
      extremity or (2) a procedure code for a lower or upper limb amputation in
      combination with a principal diagnosis of an extremity injury or injury-related
      complication. RESULTS: Incidence of major amputations declined 3.4% (p < .05)
      annually from 1.88 per 100,000 in 1979 to 1.07 per 100,000 in 1993. Incidence of
      minor amputations declined 4.8% (p < .05) annually from 10.8 per 100,000 in 1979
      to 4.7 per 100,000 in 1993. Acute care length of stay for trauma-related
      amputations declined 40% over the study period and was significantly affected by
      the patient's payer source, amputation level, and injury characteristics. Of the
      patients with a major amputation, 15% were discharged to inpatient
      rehabilitation; 60% were discharged directly home. More proximal amputation
      levels, presence of severe injuries to other body systems, and acute care at a
      designated trauma center significantly increased the likelihood of disposition to
      inpatient rehabilitation. The leading causes of trauma-related amputation were
      injuries involving machinery (40.1%), powered tools and appliances (27.8%),
      firearms (8.5%), and motor vehicle crashes (8%). CONCLUSIONS: Findings suggest a
      substantial decline in incidence rates of both major and minor amputations over
      the 15-year study period, a low rate of disposition to inpatient rehabilitation
      services of patients sustaining major amputations, and an apparent role of
      firearms as a cause of trauma-related amputations in patients younger than 25
      years of age. The consequences of increasingly shorter acute care hospital stays
      and low rates of discharge to inpatient rehabilitation on the long-term outcomes
      of persons who have had traumatic amputation should be examined.

PMID- 9523781
TI  - Resistive inspiratory muscle training in subjects with chronic cervical spinal
      cord injury.
AB  - OBJECTIVE: To determine whether pulmonary function, respiratory muscle strength,
      and dyspnea can be improved in individuals with chronic cervical spinal cord
      injury (SCI). STUDY DESIGN: Ten subjects participated in an 8-week resistive
      inspiratory muscle training (IMT) program for 15 minutes twice daily. Spirometry,
      lung volumes, maximum inspiratory pressure (MIP), maximum expiratory pressure
      (MEP), and dyspnea were measured at baseline, week 4, and week 8. Six months
      after the study, spirometry, MIP, and MEP were re-measured in a subgroup of the
      original participants. RESULTS: We found that regular IMT in subjects with
      cervical SCI significantly improved forced vital capacity (means +/- SE) (11% +/-
      2.82% increase), forced inspiratory vital capacity (21% +/- 6.91%), vital
      capacity (8% +/- 4.36%), total lung capacity (12% +/- 3.23%), functional residual
      capacity (15% +/- 5.96%), and MIP (24% +/- 6.98%) (p < .05). Furthermore,
      although no statistical differences were observed for the dyspnea scale, the fact
      that subjects reported decreased levels (43% +/- 21.30% reduction) of perceived
      difficulty breathing may be of greater importance. No significant differences
      from baseline values were found in the seven subjects whose spirometry and
      respiratory muscle strength were measured 6 months after the study. CONCLUSIONS:
      Our findings suggest that in individuals with cervical SCI regular resistive IMT
      may result in decreased restrictive ventilatory impairment and reported dyspnea
      and, thus, reduced incidence of chronic respiratory complaints, respiratory
      infection, and other pulmonary complications.

PMID- 9523782
TI  - Outcomes in the first 5 years after traumatic brain injury.
AB  - OBJECTIVE: To examine the extent to which outcomes from traumatic brain injury
      differ as a function of time and can be predicted at discharge from inpatient
      rehabilitation. DESIGN: Survey method employing cross-sectional analyses.
      SETTING: An inpatient brain injury rehabilitation unit in a large midwestern
      academic medical center. SUBJECTS: Ninety-five adults with traumatic brain
      injuries, 6 months to 5 years after inpatient rehabilitation, stratified by time
      postdischarge. MAIN OUTCOME MEASURES: Functional Independence Measure (FIM),
      Sickness Impact Profile (SIP), Medical Outcomes Survey SF-36, Community
      Integration Questionnaire (CIQ), Craig Handicap Assessment and Reporting
      Technique (CHART), Brief Symptom Inventory (BSI), Satisfaction With Life Scale
      (SWLS), and indices of current psychosocial functioning. RESULTS: Substance
      abuse, need for supervision, life satisfaction, and selected subscales of the CIQ
      and CHART differed over the period 6 months to 5 years after discharge.
      Approximately 75% of the variance in current FIM scores, and 40% to 50% of CHART,
      CIQ, and SIP total scores, could be predicted at time of discharge. CONCLUSIONS:
      Outcomes over the first 5 years after discharge were dynamic, with most change
      being improvement, at least after the first 2 years. Important aspects of outcome
      could not be predicted based on premorbid characteristics, injury severity, and
      initial functional abilities.

PMID- 9523783
TI  - Predicting acute denervation in carpal tunnel syndrome.
AB  - OBJECTIVE: To determine which nerve conduction parameters can predict the
      presence of acute denervation in carpal tunnel syndrome. SETTING: The
      electrodiagnostic laboratories of a hospital and a county hospital district.
      DESIGN: A retrospective review. PATIENTS: A total of 1,590 consecutive cases from
      January 1992 to June 1996, diagnosed as having median neuropathy at the wrist.
      MAIN OUTCOME MEASURES: Evidence of acute denervation on needle electromyography
      of the abductor pollicis brevis and its relationship to patient age, gender, and
      parameters obtained from nerve conduction studies, including median sensory
      latency and amplitude, and median motor latency and amplitude. RESULTS: Logistic
      regression analysis identified gender, median motor latency, and median motor
      amplitude (all p < or = .008) as contributing to the prediction of denervation.
      Needle examination of the cases with a median motor amplitude <7 mV detected
      95.3% (141/148) of all cases with denervation and could have spared 52%
      (708/1,362) of the population from a needle examination of the abductor pollicis
      brevis. CONCLUSION: The median motor amplitude can predict the presence of acute
      denervation in the thenar muscles in median neuropathy at the wrist and possibly
      eliminate a painful needle examination of the median-innervated thenar muscles in
      over 50% of the cases.

PMID- 9523784
TI  - Seat interface pressures of individuals with paraplegia: influence of dynamic
      wheelchair locomotion compared with static seated measurements.
AB  - OBJECTIVE: To provide a comparison of the seat interface pressures between static
      seating and dynamic seating during wheelchair locomotion of individuals with
      paraplegia. DESIGN: Repeated measures multivariate analysis of variance (MANOVA)
      comparing two conditions: static seat and dynamic seat interface pressures.
      SETTING: University campus and clinic. PARTICIPANTS: Fifteen participants, each
      of whom propelled a manual wheelchair for at least 5 hours per week over the
      previous 6 months and functioned with a spinal cord injury/ disability level of
      T1 or below. MAIN OUTCOME MEASURES: Peak pressure (PP) and pressure time integral
      (PTI) as measured by the Novel Pliance System, which consists of a flexible 32 x
      32 capacitive sensor mat (each sensor 1.5 cm2) interfaced with a PC, was sampled
      at 10Hz. The participants were measured in their own wheelchair with a new Jay
      Active seat cushion. RESULTS: The repeated measures MANOVA showed a difference in
      the PP and PTI between the static and dynamic measurements (Wilk's = .00, p <
      .05). Follow-up dependent t tests yielded a difference in PP (t = 5.40, p <
      0.025) and no difference in the PTI between static and dynamic conditions (t =
      1.45, p > 0.025). The PP during static seating (mean = 16.2 +/- 5.0 kPa [121 +/-
      37.5 mmHg]) was less than during dynamic seat interface pressures during
      wheelchair locomotion (20.03 +/- 6.6 kPa [152.3 +/- 49.5 mmHg]). PP varied by up
      to 42% during the wheelchair locomotion cycle. The PTI was similar between static
      (30.1 +/- 9.3 kPa [225.75 +/- 69 mmHg]) and dynamic conditions (36.2 +/- 18.1 kPa
      [271 +/- 135.7 mmHg]). CONCLUSIONS: The results from this study are consistent
      with some of the previous work on the nondisabled and a single case study, but
      with greater external validity because of the nature of the sample chosen and the
      methodology employed. PPs were greater during dynamic wheelchair locomotion
      compared with static seating interface pressures, with the peak varying up to 42%
      during the wheelchair locomotion cycle. The PTI indicates that the cumulative
      effect of the loading was comparable between conditions. The question that
      remains is whether this dynamic loading, resulting in a change in PP throughout
      the cycle, has a significant effect on tissue health.

PMID- 9523785
TI  - Biomechanical gait alterations independent of speed in the healthy elderly:
      evidence for specific limiting impairments.
AB  - OBJECTIVES: It is not known whether changes in the biomechanics of elderly gait
      are related to aging per se, or to reduced walking speed in this population. The
      goals of the present study were to identify specific biomechanical changes,
      independent of speed, that might impair gait performance in healthy older people
      by identifying age-associated changes in the biomechanics of gait, and to
      determine which of these changes persist at increased walking speed. DESIGN:
      Stereophotogrammetric and force platform data were collected. Differences in peak
      joint motion (kinematic) and joint moment and power (kinetic) values between
      healthy young and elderly subjects at comfortable and increased walking speed
      were measured. SETTING: A gait laboratory. SUBJECTS: Thirty-one healthy elderly
      (age 65 to 84 years) and 31 healthy young adult subjects (age 18 to 36 years),
      all without known neurologic, musculoskeletal, cardiac, or pulmonary problems.
      MAIN OUTCOME MEASURES: All major peak kinematic and kinetic variables during the
      gait cycle. RESULTS: Several kinematic and kinetic differences between young and
      elderly adults were found that did not persist when walking speed was increased.
      Differences that persisted at both comfortable and fast walking speeds were
      reduced peak hip extension, increased anterior pelvic tilt, and reduced ankle
      plantarflexion and ankle power generation. CONCLUSION: Gait performance in the
      elderly may be limited by both subtle hip flexion contracture and ankle
      plantarflexor concentric weakness. Results of the current study should motivate
      future experimental trials of specific hip flexor stretching and ankle
      plantarflexor concentric strengthening exercises to preserve and potentially
      improve walking performance in the elderly.

PMID- 9523786
TI  - Self-directed strength training: its effect on leg strength in men with mental
      retardation.
AB  - OBJECTIVE: To compare isokinetic measures of peak torque (newton-meters) and
      total work (joules) in men with mental retardation on a test of knee extension
      after 12 weeks of trainer-directed training and 1 year of self-directed training.
      DESIGN: Repeated measures of analysis of variance using a planned comparison
      approach involving an independent 2 x 3 (group x test) design. SETTING: Subjects
      were tested at a university athletic training facility on three separate days.
      SUBJECTS: Volunteer sample of 12 subjects with mental retardation: 6 in strength
      training group, 6 in control group. INTERVENTION: Subjects performed an
      isokinetic knee extension test at a velocity of 60 degrees/sec on three separate
      days. Test 1 was the pretest, test 2 was conducted after 12 weeks of trainer
      directed hydraulic resistance training, and test 3 was conducted after 1 year of
      self-directed hydraulic resistance training. RESULTS: For both isokinetic
      parameters measured, the strength-trained subjects demonstrated significantly
      higher scores after 12 weeks of training and after 1 year of training than the
      scores achieved on the pretest. No significant differences in peak torque or
      total work scores were found between test 2 and test 3 scores for the strength
      trained group. No significant changes in isokinetic scores between test sessions
      were found for the control subjects. CONCLUSION: Men with mental retardation can
      maintain strength following a self-directed hydraulic resistance strength
      training program.

PMID- 9523787
TI  - Impairment and disability: their relation during stroke rehabilitation.
AB  - OBJECTIVES: To describe the association between impairment and disability during
      stroke rehabilitation and to examine the effects of rehabilitation by studying
      the degree of disability reduction experienced by stroke patients who did not
      have significant reductions in impairment levels. DESIGN: Statistical analysis of
      items from a database of prospectively collected information on stroke patients
      admitted for rehabilitation. SETTING: Large urban academic freestanding
      rehabilitation facility. PARTICIPANTS: Four hundred two patients consecutively
      admitted for comprehensive acute stroke inpatient rehabilitation. MAIN OUTCOME
      MEASURES: The National Institutes of Health Stroke Scale (NIHSS) was used to
      measure impairment and the Functional Independence Measure (FIM) was used to
      measure disability. Motor and cognitive subscales of the FIM instrument were
      evaluated. Raw NIHSS and FIM scores were converted to linear measures using Rasch
      analysis. METHODS: Relationships were studied between converted NIHSS and the two
      FIM subscales for admission, discharge, and change scores using linear regression
      analysis. In a second analysis, two groups of patients were identified; the 342
      patients who experienced no substantial reduction of impairment comprised the "no
      impairment reduction (NIR) group," and the 60 patients who had a significant
      reduction of impairment level comprised the "impairment reduction (IR) group."
      Multivariate analysis of variance was used to determine and compare the amount of
      change in motor and cognitive FIM measures over time for each of the two groups.
      RESULTS: NIHSS correlated significantly with motor and cognitive FIM subscores
      for admission, discharge, and change measures; R2 values ranged between .02 and
      .36. Both the NIR group and the IR group experienced significant decreases in
      disability during rehabilitation. The differences in discharge FIM measures
      between the two groups were relatively small. CONCLUSIONS: Although stroke
      related impairment and disability are significantly correlated with each other,
      reduced impairment level alone does not fully explain the reduced disability that
      occurs during rehabilitation. Even patients without substantial impairment
      reduction demonstrate disability reduction during rehabilitation, suggesting that
      rehabilitation has an independent role in improving function beyond that
      explained by neurologic recovery alone.

PMID- 9523788
TI  - Myofascial trigger points in intercostal muscles secondary to herpes zoster
      infection of the intercostal nerve.
AB  - Chronic pain in the chest wall is a major complication after herpes zoster
      infection of intercostal nerves. It is usually difficult to control pain of such
      origin. Two cases are reported of postherpetic neuralgia after herpes zoster
      infection involving the intercostal nerves. Both patients had shooting, burning,
      aching, and localized pain in the muscle supplied by the involved intercostal
      nerves 1 to 3 months after onset. Compression palpation of a tender spot in one
      of these muscles induced a referred pain that followed the corresponding
      interspace, usually in the distal anterior direction. Local twitch responses
      could be elicited during injection of 0.5% or 1% lidocaine into one of these
      tender spots; the pain in the interspace was consistently eliminated immediately
      after injection. One patient had complete pain relief after three series of
      injections. The effect of pain relief for the other patient lasted for 1 to 2
      weeks after the initial injection and lasted progressively longer (up to 2
      months) after repeated injections. It appears that many of the tender spots
      formed in intercostal muscles after herpes zoster are myofascial trigger points
      that respond to injection with referred pain, local twitch responses, and
      immediate pain relief.

PMID- 9523789
TI  - Recurrent spontaneous hemarthrosis associated with reflex sympathetic dystrophy.
AB  - Reflex sympathetic dystrophy is a mysterious entity with unclear pathogenesis.
      The diagnosis is largely clinical and based on signs and symptoms of pain and
      vasomotor dysfunction. Treatment is a challenge because the underlying mechanism
      remains unknown. Our patient is a 75-year-old woman 2 years after left total knee
      replacement who presented with her second spontaneous hemarthrosis in 3 months.
      After arthrocentesis, dusky discoloration, edema, hyperesthesia, and decreased
      range of motion of the left knee and entire distal extremity were noted. Despite
      analgesia and physical therapy her symptoms worsened. Radiographs of her left
      knee showed severe periprosthetic osteopenia and a triple phase bone scan was
      negative. Clinically, reflex sympathetic dystrophy was considered likely and a
      lumbar sympathetic block was performed. The patient improved and continued to do
      well after a series of blocks. This is the first reported case of recurrent
      atraumatic hemarthrosis associated with reflex sympathetic dystrophy.

PMID- 9523790
TI  - Hyperhomocysteinemia as a cause of premature stroke in a young patient.
AB  - A case is presented of a woman who had an occlusive stroke at age 29. She was
      seen in a rehabilitation medicine clinic for central nervous system-mediated pain
      that had developed soon after a cerebrovascular event. After an extensive workup
      to find the cause of her cerebrovascular occlusion, it was discovered that she
      had a markedly elevated fasting plasma homocysteine level of 59 micromol/L. A
      discussion of premature vascular disease in the rehabilitation patient is
      followed by a short review of the clinical detection of, and potential therapy
      for, hyperhomocysteinemia.

PMID- 9523791
TI  - Neuropharmacologic treatment of hemineglect: a case report comparing
      bromocriptine and methylphenidate.
AB  - Individuals who have hemineglect fail to attend to stimuli presented on the side
      of the body contralateral to a brain lesion. Although in animal studies the
      severity of neglect correlates with the degree of dopamine depletion, in
      hemineglect patients dopamine-enhancing medications have produced inconsistent
      results. We present a case of hemineglect following a right cerebrovascular
      accident in a 68-year-old man treated consecutively with methylphenidate and
      bromocriptine. Tests sensitive to neglect were administered during treatment with
      methylphenidate, then after all medications had been discontinued, then when the
      patient was taking low and moderate doses of bromocriptine, and again after all
      medications had been discontinued for 4 and 26 days. Methylphenidate was superior
      to no drug treatment. Bromocriptine produced more improvement in neglect than
      methylphenidate. Although the patient showed an exacerbation of his neglect after
      withdrawal from methylphenidate, performance gains persisted after withdrawal
      from bromocriptine. Treatment effects appear related to medication choice, timing
      of drug treatment, and the adaptability of dopaminergic receptor systems.

PMID- 9523792
TI  - Axillary hyperhidrosis: treatment with botulinum toxin A.
AB  - Hyperhidrosis can be emotionally challenging and socially and professionally
      disruptive, and there are few effective treatments. This condition was
      successfully treated with botulinum toxin in two men who, since their early
      teens, had had excessive axillary sweating, requiring frequent shirt changes.
      They received bilateral axillary injections with 100 units of botulinum toxin
      type A, and within 5 days reported cessation of excessive sweating. Quantitative
      measurements before and 2 to 4 weeks after the injections demonstrated an average
      reduction of 71% and 76% (from 11.6 to 3.4 and from 2.5 to 0.6 mL/min m2) in
      axillary sweating during rest. A 96% reduction (from 42.9 to 1.7 mL/min m2) was
      seen in one patient during mental stress. No complications developed. This study
      quantitates the reduced axillary sweating achieved through chemodenervation with
      botulinum toxin A.

PMID- 9523793
TI  - Hyperthermia, rhabdomyolysis, and disseminated intravascular coagulation
      associated with baclofen pump catheter failure.
AB  - A 29-year-old man with C6 tetraplegia (ASIA A) using an implanted baclofen pump
      and intrathecal catheter infusion system for spasticity control developed severe
      spasticity, hyperthermia, hypotension, rhabdomyolysis, and disseminated
      intravascular coagulation after catheter disconnection. Tracheal intubation and
      mechanical ventilation were necessary. Extensive workup for a concurrent
      infection was negative except for urine cultures. The patient remained febrile
      for 10 days despite empirical antibiotic trials. Administration of high-dose
      benzodiazepines was inadequate for spasticity control. Spasticity control and his
      clinical condition, including body temperature, did not improve until his
      catheter was surgically replaced and intrathecal baclofen administration was
      resumed. The pharmacopathology of abrupt baclofen withdrawal and the similarities
      between this presentation, sepsis, neuroleptic malignant syndrome, and malignant
      hyperthermia are discussed. High-dose dantrolene was not used; however, based on
      similarities between this patient's presentation and neuroleptic malignant
      syndrome, it may have been the drug of choice.

PMID- 9523794
TI  - Adverse outcomes after surgery in the year 2001--a continuing odyssey.

PMID- 9523795
TI  - A rabbit model of the brain and cardiopulmonary bypass: the bunny that just keeps
      going and going and going...

PMID- 9523796
TI  - Optical isomers open a new window on anesthetic mechanism.

PMID- 9523797
TI  - Rural realities.

PMID- 9523798
TI  - Myocardial infarction after noncardiac surgery.
AB  - BACKGROUND: In this study, the authors intensively monitored isoenzyme and
      electric activity of the heart for the first 7 days after noncardiac surgery in a
      large group of patients at risk for postoperative myocardial infarction (PMI).
      METHODS: After institutional review board approval and written informed consent
      were received, 323 patients, aged 50 yr or older, who had ischemic heart disease
      and presented for noncardiac surgery, were enrolled in this prospective, blinded
      study. After operation, patients had daily clinical assessments,
      electrocardiograms, and measurements of creatine kinase (CK), CK-2 (mass and
      activity), and Troponin-T on the operative night, twice daily on postoperative
      days 1-4, and then daily on days 5-7. A diagnosis of PMI was made if the total CK
      was > 174 U/l and in the presence of two of the following: (1) CK-2/CK (mass or
      activity) > 5%, (2) new Q waves lasting > or = 0.04 s and 1 mm deep in at least
      two contiguous leads, (3) Troponin-T was > 0.2 microg/l, or (4) a positive result
      of pyrophosphate scan. RESULTS: Eighteen of the 323 patients (5.6%) had a PMI, of
      which 3 (17%) were fatal. Only 3 of 18 patients had chest pain, whereas 10 of 18
      patients (56%) had other clinical findings. The electrocardiographic
      classification of the PMI was Q wave in 6, non-Q wave in 10, and indeterminate in
      2. The PMIs occurred on the day of operation in 8, on day one in 6, on day two in
      3, and on day four in 1 patient. CONCLUSIONS: This study determined that PMI was
      an early event, only occasionally associated with chest pain, and usually non-Q
      wave in nature.

PMID- 9523799
TI  - The sensitivity and specificity of the caffeine-halothane contracture test: a
      report from the North American Malignant Hyperthermia Registry. The North
      American Malignant Hyperthermia Registry of MHAUS.
AB  - BACKGROUND: The caffeine-halothane contracture test (CHCT) is the only recognized
      laboratory test to diagnose malignant hyperthermia (MH). The authors report the
      results of their analysis of pooled data from the North American Malignant
      Hyperthermia Registry database to determine the sensitivity and specificity of
      the CHCT. METHODS: The MH Clinical Grading Scale was used to identify 32 case
      subjects who were "almost certain" to be MH susceptible based on clinical
      criteria alone. Their CHCT results were compared with those of a group of 120
      control subjects considered to be at low risk for MH. Diagnostic thresholds of
      the CHCT were adjusted, and its component tests were combined to generate
      receiver operating characteristic curves. The maximal Youden index for each
      component test was chosen as the diagnostic threshold indicative of MH
      susceptibility. RESULTS: The highest sensitivity (97%; 95% CI, 84-100%) was
      achieved with a two-component test with thresholds of > or = 0.5 g contracture
      for 3% halothane, > or = 0.3 g contracture at 2 mM caffeine, or both, considered
      positive for MH. The test specificity was 78% (95% CI, 69-85%). The addition of
      other CHCT component tests did not improve CHCT sensitivity or specificity.
      CONCLUSION: The CHCT achieves high sensitivity and acceptable specificity as a
      clinical laboratory diagnostic test when it is performed according to published
      standards. However, it cannot be used as a screening test because of the low
      prevalence of MH in the general population.

PMID- 9523800
TI  - Bayesian modeling of muscle biopsy contracture testing for malignant hyperthermia
      susceptibility.
AB  - BACKGROUND: Phenotyping malignant hyperthermia (MH) by contracture testing has a
      low but quantifiable degree of inaccuracy, measured by its sensitivity and
      specificity. Quantifying the limitations inherent in diagnostic testing for MH
      can help resolve issues in clinical practice, such as the interpretation of a
      negative test and the apparent lack of complete genetic linkage to RYR1. METHODS:
      Bayesian models, mathematical descriptions of the outcome of diagnostic testing,
      were constructed. The inputs to the model include patient factors, summarized in
      a single number called pretest probability (PTP), and sensitivity and specificity
      that specify the accuracy of the entire test process. The outputs of the model
      include positive predictive value (PPV) and negative predictive value (NPV),
      which are numeric expressions of diagnostic certainty of positive and negative
      test results. A special case was constructed for equivocal results. RESULTS: The
      PPV, NPV, and efficiency of contracture testing for MH are functions of PTP,
      sensitivity, and specificity. The NPV is high for all clinical PTP, whereas PPV
      is clinically useful for moderate to high PTP. CONCLUSIONS: Diagnostic
      contracture testing for MH is clinically useful because of high NPV and can
      exclude MH with near certainty. For MH probands, the clinical grading scale for
      MH may guide PTP estimation, whereas for relatives of probands, PTP is a function
      of kinship to a known MH-susceptible relative. A sequential testing strategy
      optimizes diagnostic information by maximizing PTP within a pedigree. Incomplete
      testing of parents of an MH susceptible child can pose a significant risk of
      false-negative results for the untested parent. Even with optimal pedigree
      testing strategies, the PPV drift effect results in a considerable source of
      phenotypic uncertainty for genetic linkage studies.

PMID- 9523801
TI  - Absence of biochemical evidence for renal and hepatic dysfunction after 8 hours
      of 1.25 minimum alveolar concentration sevoflurane anesthesia in volunteers.
AB  - BACKGROUND: Sevoflurane is degraded by carbon dioxide absorbents to a
      difluorovinyl ether (compound A) that can cause renal and hepatic injury in rats.
      The present study applied sensitive markers of renal and hepatic function to
      determine the safety of prolonged (8 h), high concentration (3% end-tidal)
      sevoflurane anesthesia in human volunteers. METHODS: Thirteen healthy male
      volunteers provided informed consent to undergo 8 h of 1.25 minimum alveolar
      concentration sevoflurane anesthesia delivered with a fresh gas flow of 2 l/min.
      Glucose, protein, albumin, N-acetyl-beta-D-glucosaminidase (NAG), and alpha- and
      pi-glutathione-S-transferase (GST) levels were analyzed in urine collected at 24
      h before and for 3 days after sevoflurane anesthesia. Daily blood samples were
      analyzed for creatinine, blood urea nitrogen (BUN), alanine aminotransferase,
      alkaline phosphatase, and bilirubin concentrations. Circuit compound A and plasma
      fluoride concentrations were measured. RESULTS: During anesthesia, average and
      maximum inspired compound A concentrations were 27 +/- 7 and 34 +/- 6 (mean +/-
      SD) and median mean blood pressure, esophageal temperature, and end-tidal carbon
      dioxide levels were 63 mmHg, 36.8 degrees C, and 32 mmHg, respectively. The
      average serum inorganic fluoride concentration 2 h after anesthesia was 66.2 +/-
      14.7 microM. Results of tests of hepatic function and renal function (BUN,
      creatinine concentration) were unchanged after anesthesia. Glucose, protein,
      albumin, and NAG excretion were not significantly increased after anesthesia.
      Urine concentrations of alpha-GST and pi-GST were increased on day 1 after
      anesthesia and alpha-GST was increased on day 2 after anesthesia but returned to
      normal afterward. CONCLUSIONS: Prolonged (8 h), high concentration (3%)
      sevoflurane anesthesia administered to volunteers in a fresh gas flow of 2 l/min
      does not result in clinically significant changes in biochemical markers of renal
      or hepatic dysfunction.

PMID- 9523802
TI  - Cysteine conjugate beta-lyase-dependent metabolism of compound A (2
      [fluoromethoxy]-1,1,3,3,3-pentafluoro-1-propene) in human subjects anesthetized
      with sevoflurane and in rats given compound A.
AB  - BACKGROUND: Sevoflurane undergoes Baralyme- or soda lime-catalyzed degradation in
      the anesthesia circuit to yield compound A (2-[fluoromethoxy]-1,1,3,3,3
      pentafluroro-1-propene), which is nephrotoxic in rats and undergoes metabolism
      via the cysteine conjugate beta-lyase pathway in those animals. The objective of
      these experiments was to test the hypothesis that compound A undergoes beta-lyase
      dependent metabolism in humans. METHODS: Human volunteers were anesthetized with
      sevoflurane (1.25 minimum alveolar concentration, 3%, 2 l/min, 8 h) and thereby
      exposed to compound A. Urine was collected at 24-h intervals for 72 h after
      anesthesia. Rats, which served as a positive control, were given compound A
      intraperitoneally, and urine was collected for 24 h afterward. Human and rat
      urine samples were analyzed by 19F nuclear magnetic resonance spectroscopy and
      gas chromatography-mass spectrometry for the presence of compound A metabolites.
      RESULTS: Analysis of human and rat urine showed the presence of the compound A
      metabolites S-[2(fluoromethoxy)-1,1,3,3,3-pentafluoropropyl]-N-acetyl-L-
      cysteine, (E)- and (Z)-S-[2-(fluoromethoxy)-1,3,3,3-tetrafluoro-1-propenyl]-N
      acetyl- L-cysteine, 2-(fluoromethoxy)-3,3,3-trifluoropropanoic acid, 3,3,3
      trifluorolactic acid, and inorganic fluoride. The presence of 2
      (fluoromethoxy)3,3,3-trifluoropropanoic acid and 3,3,3-trifluorolactic acid in
      human urine was confirmed by gas chromatography-mass spectrometry. CONCLUSIONS:
      The formation of compound A-derived mercapturates shows that compound A undergoes
      glutathione S-conjugate formation. The identification of 2-(fluoromethoxy)-3,3,3
      trifluoropropanoic acid and 3,3,3-trifluorolactic acid in the urine of humans
      anesthetized with sevoflurane shows that compound A undergoes beta-lyase
      dependent metabolism. Metabolite formation was qualitatively similar in both
      human volunteers anesthetized with sevoflurane, and thereby exposed to compound
      A, and in rats given compound A, indicating that compound A is metabolized by the
      beta-lyase pathway in both species.

PMID- 9523803
TI  - Transient neurologic symptoms after spinal anesthesia with mepivacaine and
      lidocaine.
AB  - BACKGROUND: Spinal anesthesia with lidocaine is ideal for ambulatory surgery
      because of its short duration of action. However, transient neurologic symptoms
      (TNS) occur in 0-40% of patients. The incidence of TNS with mepivacaine, which
      has a similar duration of action, is unknown. METHODS: Sixty ambulatory patients
      undergoing knee arthroscopy received spinal anesthesia in a randomized, double
      blinded manner, with either 45 mg 1.5% mepivacaine or 60 mg 2% lidocaine. An L3
      L4 midline approach was used with a 27-gauge Whitacre needle and a 20-gauge
      introducer. The local anesthetic was injected over approximately 30 s with the
      aperture of the Whitacre needle in a cephalad direction. Two to 4 days after
      operation, each patient was questioned about the development of TNS. In addition,
      the two groups were compared for time to regression of sensory and motor blockade
      and time to discharge milestones. RESULTS: Three patients receiving lidocaine
      were lost to follow-up. None of the 30 patients in the mepivacaine group
      developed TNS, whereas 6 of 27 (22%) in the lidocaine group did (P = 0.008). Time
      to regression to the L5 sensory level and to complete resolution of motor block
      were similar in both groups. The times to discharge milestones were also
      comparable. CONCLUSIONS: The incidence of TNS is greater with 2% lidocaine than
      with 1.5% mepivacaine for patients having unilateral knee arthroscopy under
      spinal anesthesia. Mepivacaine seems to be a promising alternative to lidocaine
      for outpatient surgical procedures because of its similar duration of action.
      Further studies are warranted to determine the optimal dose of intrathecal
      mepivacaine for ambulatory surgery and the incidence of TNS with other doses and
      concentrations of intrathecal mepivacaine.

PMID- 9523804
TI  - Incidence of transient neurologic symptoms after hyperbaric subarachnoid
      anesthesia with 5% lidocaine and 5% prilocaine.
AB  - BACKGROUND: Hyperbaric 5% lidocaine has been associated with transient neurologic
      symptoms (TNSs) after spinal anesthesia. A prospective, masked, randomized study
      was conducted to compare the incidence of TNSs after spinal anesthesia with
      hyperbaric 5% lidocaine or 5% prilocaine to assess the utility of prilocaine as
      an alternative to lidocaine in patients having short surgical procedures.
      METHODS: The number of patients to be enrolled (100 per group) was determined by
      power analysis (80%, P = 0.05) considering an incidence of TNSs after spinal
      anesthesia with lidocaine of at least 11% according to data reported in other
      studies. Two hundred patients scheduled for elective surgery expected to last <60
      min were allocated at random to receive spinal anesthesia with hyperbaric 5%
      lidocaine or hyperbaric 5% prilocaine. Three to 5 days after spinal anesthesia,
      all patients were interviewed by an anesthesiologist who was blinded to the group
      assignment and details of the anesthetic and surgical technique using a
      standardized symptom checklist. Patients with symptoms underwent neurologic
      examination. RESULTS: Both groups were comparable with regard to demographic data
      and details of the surgical and anesthetic procedures. The incidence of TNSs in
      both groups was low and differences were not found (4% in the lidocaine group and
      1% in the prilocaine group). The mean age of patients with TNSs (58 yr) was
      higher than that of patients without TNSs (48 yr; P < 0.05). No relation with any
      of the other variables was found. CONCLUSIONS: The low incidence of TNSs among
      lidocaine-anesthetized patients (4%) may account for the lack of significant
      differences between hyperbaric 5% lidocaine and 5% prilocaine and to the
      insufficient power of the study to exclude the possibility of a type II error.

PMID- 9523805
TI  - Transient neurologic symptoms after spinal anesthesia: a lower incidence with
      prilocaine and bupivacaine than with lidocaine.
AB  - BACKGROUND: Recent evidence suggests that transient neurologic symptoms (TNSs)
      frequently follow lidocaine spinal anesthesia but are infrequent with
      bupivacaine. However, identification of a short-acting local anesthetic to
      substitute for lidocaine for brief surgical procedures remains an important goal.
      Prilocaine is an amide local anesthetic with a duration of action similar to that
      of lidocaine. Accordingly, the present, prospective double-blind study compares
      prilocaine with lidocaine and bupivacaine with respect to duration of action and
      relative risk of TNSs. METHODS: Ninety patients classified as American Society of
      Anesthesiologists physical status I or II who were scheduled for short
      gynecologic procedures under spinal anesthesia were randomly allocated to receive
      2.5 ml 2% lidocaine in 7.5% glucose, 2% prilocaine in 7.5% glucose, or 0.5%
      bupivacaine in 7.5% glucose. All solutions were provided in blinded vials by the
      hospital pharmacy. Details of spinal puncture, extension and regression of spinal
      block, and the times to reach discharge criteria were noted. In the evening of
      postoperative day 1, patients were evaluated for TNSs by a physician unaware of
      the drug administered and the details of the anesthetic procedure. RESULTS: Nine
      of 30 patients receiving lidocaine experienced TNSs, 1 of 30 patients receiving
      prilocaine (P = 0.03) had them, and none of 30 patients receiving bupivacaine had
      TNSs. Times to ambulate and to void were similar after lidocaine and prilocaine
      (150 vs. 165 min and 238 vs. 253 min, respectively) but prolonged after
      bupivacaine (200 and 299 min, respectively; P < 0.05). CONCLUSIONS: Prilocaine
      may be preferable to lidocaine for short surgical procedures because it has a
      similar duration of action but a lower incidence of TNSs.

PMID- 9523806
TI  - The response to repeated nitric oxide inhalation is inconsistent in patients with
      acute respiratory distress syndrome.
AB  - BACKGROUND: Nitric oxide (NO) is administered frequently in patients with acute
      respiratory distress syndrome (ARDS) and pulmonary hypertension. The efficacy of
      this therapy over several days is not well known. The authors first determined
      the consistency of the response to repeated administration of NO and then the
      baseline variables that were associated with improvement in patients with severe
      ARDS. METHODS: In a prospective trial, 32 mechanically ventilated patients with
      severe ARDS received 10 parts per million NO by inhalation. In 22 of these
      patients, its effect was tested repeatedly (up to four times) in several days.
      Improvement was defined as an increase >10% in the ratio of pressure of oxygen in
      arterial blood (P(aO2)) to the inspiratory pressure of oxygen (FIO2) from
      baseline. Patients showing such an improvement were maintained on NO inhalation.
      RESULTS: Twelve of the 22 patients (54%) showed a clinically significant and
      reproducible increase in the P(aO2)/FIO2 ratio with NO, from 74 +/- 30 mmHg (mean
      +/- SD) to 95 +/- 41 mmHg (P < 0.001). In three patients (14%), P(aO2) did not
      improve, even with multiple exposures. In seven patients (32%), an inconsistent
      response was seen on different days. Mean pulmonary artery pressure decreased for
      the entire group from 34 +/- 10 mmHg to 29 +/- 9 mmHg (P < 0.01), but this
      decrease did not correlate with the increase in P(aO2) in individual patients.
      The baseline P(aO2)/FIO2 ratio and mixed venous oxygenation (P(vO2)) were
      significantly lower, and the venous admixture was greater in patients showing
      beneficial effects of NO inhalation on P(aO2). CONCLUSIONS: Repeated NO
      inhalation caused a consistent improvement in P(aO2) in about one half of these
      patients with severe ARDS; no significant benefit or inconsistent effects on
      pulmonary gas exchange were noted in the others. These findings could be related
      to the complexity of the mechanisms regulating the vasomotor changes in this
      syndrome. Severe baseline hypoxemia may be associated with a more favorable
      effect of NO on P(aO2).

PMID- 9523807
TI  - Electroencephalographic derivatives as a tool for predicting the depth of
      sedation and anesthesia induced by sevoflurane.
AB  - BACKGROUND: The electroencephalogram (EEG) has been evaluated as a tool for
      measuring depth of anesthesia, but the use of the EEG monitoring is still
      controversial. The current study was designed to evaluate the accuracy of three
      EEG parameters and anesthetic concentration for predicting depth of sedation and
      anesthesia during sevoflurane anesthesia METHODS: One low and one high
      equilibrated concentration ranging from 0.2-1.8% were assigned randomly and
      administered consecutively to 69 patients. The bispectral index (BIS; version
      3.2), 95% spectral edge frequency (SEF), and median power frequency (MPF) were
      obtained from a bipolar frontomastoid (Fp1-A1, Fp2-A2) montage using an EEG
      monitor. Sedation was assessed using the responsiveness portion of the observer's
      assessment of alertness-sedation scale. In the second phase of the study, the 47
      patients who were scheduled to have skin incisions were observed for purposeful
      movement in response to skin incision at sevoflurane concentrations between 1.6%
      and 2.4%. The relation among BIS, 95% SEF, MPF, sevoflurane concentration,
      sedation score, and movement or no movement after skin incision, was determined.
      Prediction probability values for EEG parameters and sevoflurane concentration to
      predict depth of sedation and anesthesia were also calculated. RESULTS: The BIS
      and sevoflurane concentration correlated closely with the sedation score. Both
      95% SEF and MPF changed significantly but biphasically with increasing sedation.
      The prediction probability values for BIS and sevoflurane concentration were
      0.966 and 0.945, respectively, indicating a high predictive performance for depth
      of sedation. No EEG parameters predicted movement after skin incision better than
      chance alone. CONCLUSIONS: Parameters derived from EEG, such as BIS, and 95% SEF
      are reliable guides to the depth of sedation, but not to the adequacy of
      anesthesia level for preventing movement during sevoflurane anesthesia.

PMID- 9523808
TI  - Intrathecal clonidine combined with sufentanil for labor analgesia.
AB  - BACKGROUND: Intrathecal sufentanil provides rapid-onset and complete analgesia
      for the first stage of labor. The dose required to produce this effect can be
      associated with maternal respiratory depression, hypotension, nausea, or
      pruritus. Because clonidine potentiates the analgesic effects of opioids without
      increasing their side effects, the authors wanted to determine the efficacy of
      low doses of intrathecal clonidine (15 and 30 microg) combined with sufentanil.
      METHODS: Ninety-eight parturient requesting labor analgesia were studied. In a
      combined spinal-epidural technique, patients were randomly assigned to receive
      one of the following intrathecal solutions: either 15 microg clonidine (n = 10);
      30 microg clonidine (n = 10); 2.5 microg sufentanil (n = 13); 5 microg sufentanil
      (n = 13); 2.5 microg sufentanil and 15 microg clonidine (n = 13); 2.5 microg
      sufentanil and 30 microg clonidine (n = 13); 5 microg sufentanil and 15 microg
      clonidine (n = 13); or 5 microg sufentanil and 30 microg clonidine (n = 13).
      Visual analog scores for pain, blood pressure, heart rate, sensory levels,
      incidence of nausea and pruritus, and motor blockade, and maternal and cord blood
      concentrations of clonidine were recorded. RESULTS: Patients receiving 30 microg
      intrathecal clonidine with 2.5 or 5 microg intrathecal sufentanil had
      significantly longer-lasting analgesia (145 +/- 36 and 145 +/- 43 min vs. 104 +/-
      35 for those receiving 5 microg intrathecal sufentanil alone). Clonidine levels
      were undetectable in maternal serum. CONCLUSIONS: Thirty micrograms of
      intrathecal clonidine combined with 2.5 or 5 microg intrathecal sufentanil
      significantly increased the duration of analgesia during the first stage of labor
      without adverse maternal or fetal effects.

PMID- 9523809
TI  - Application of physiologic models to predict the influence of changes in body
      composition and blood flows on the pharmacokinetics of fentanyl and alfentanil in
      patients.
AB  - BACKGROUND: The influence of changes in the physiologic state of a patient on the
      disposition of fentanyl and alfentanil is poorly understood. The aims of this
      study were to determine whether physiologic pharmacokinetic models for fentanyl
      and alfentanil, based on data from rats, could predict plasma concentrations of
      these opioids in humans and to determine how changes in physiology would
      influence the predictions of their disposition. METHODS: The predictions of the
      models were tested against plasma concentration data from published
      pharmacokinetic studies. The influences of changes in body composition, cardiac
      output, and regional blood flows on the disposition of the opioids were
      simulated. RESULTS: The models could predict independently measured plasma
      concentrations of the opioids after short infusions in humans. Simulations then
      predicted that differences in body composition between men and women would have
      little influence on the pharmacokinetics of the opioids. Changes in cardiac
      output would affect drug redistribution, and consequently the early decay of the
      plasma concentrations, but not markedly influence rates of elimination. Further,
      the clearance of the opioids would decrease and their volumes of distribution
      increase with the age of the patient, but this would only marginally affect the
      early disposition of the drugs. Even large fluctuations in peripheral or hepatic
      blood flows would have modest effects on arterial plasma concentrations of the
      opioids, and sudden "postoperative" increases in peripheral blood flows would
      cause minor secondary plasma concentration peaks. CONCLUSIONS: The ability of the
      physiologic models to predict plasma concentrations of fentanyl and alfentanil in
      humans was confirmed. When changes in physiologic condition were simulated,
      effects on the pharmacokinetics of the opioids with possible implications for
      dosing were obtained only if cardiac output was varied over a wide range.

PMID- 9523810
TI  - Povidone iodine and skin disinfection before initiation of epidural anesthesia.
AB  - BACKGROUND: Povidone iodine (PI) solution is used commonly for skin disinfection
      before epidural and spinal anesthesia. Although there have been reports
      indicating the presence of microbial contaminants in PI solution, none have
      evaluated the prevalence of PI contamination. The aims of this study were to
      assess the frequency of bacterial contamination of previously opened bottles of
      PI solution and to compare the effectiveness of new and previously opened bottles
      of PI solution for skin disinfection. METHODS: Twenty previously opened and ten
      previously unopened multiple-use bottles of PI solution were evaluated for
      microbial contamination. In addition, final swabs and PI solution used for skin
      disinfection in 80 patients undergoing elective epidural analgesia were
      evaluated. RESULTS: The inside of the bottle cap or the PI solution from 40% of
      the multiple-use PI bottles in use were contaminated. There was no growth from
      any previously unused PI bottles. Povidone iodine from newly opened bottles
      provided more effective skin decontamination than did solution from previously
      opened bottles. CONCLUSIONS: Multiple-use PI bottles in normal use may become
      contaminated by bacteria. In addition, PI solution from previously opened bottles
      was less effective than PI from previously unopened bottles. Based on these
      findings, if PI solution is chosen for skin antisepsis before initiation of
      epidural and spinal anesthesia, only single-use containers should be used.

PMID- 9523811
TI  - A comparison of the intubation conditions between mivacurium and rocuronium
      during balanced anesthesia.
AB  - BACKGROUND: Comparisons of the intubation conditions with mivacurium and
      rocuronium from previous reports are confounded by the use of varied induction
      regimens. The authors compared intubation conditions of mivacurium, rocuronium,
      and a placebo at 90 s and their recovery profiles during anesthesia with nitrous
      oxide, oxygen, and propofol. METHODS: After induction with midazolam, fentanyl,
      and propofol in a randomized blinded study, 100 patients received one of the
      following treatments: 0.25 mg/kg mivacurium in divided doses (0.15 mg/kg followed
      by 0.1 mg/kg 30 s later); 0.45, 0.6, 0.9, or 1.2 mg/kg rocuronium; or placebo.
      Evoked thumb adduction was measured throughout. Intubation was attempted 90 s
      after the initial dose of mivacurium and other treatment doses by a "blinded"
      physician. Intubating conditions were graded as excellent, good, poor, or not
      possible. Spontaneous recovery was studied until a 25% initial twitch height was
      reached. Mean arterial blood pressure and heart rate changes between groups were
      determined before induction through 6 min after administration of the study
      drugs. RESULTS: There were no important changes or intergroup differences in mean
      arterial blood pressure and heart rate. Intubation conditions were good or
      excellent for both mivacurium and rocuronium at the 0.9 mg/kg dose (93%) and at
      the 1.2 mg/kg dose (100%). Rocuronium at the 0.6 mg/kg dose was excellent in 27%
      of patients, whereas rocuronium at the 0.45 mg/kg dose had the least number of
      excellent conditions and the most poor or not possible assessments. Patients
      given placebo could not be intubated. Times to maximum blockade for 0.9 and 1.2
      mg/kg rocuronium were the shortest. The times to 25% recovery for 0.6 mg/kg
      rocuronium (mean +/- SD = 27 +/- 8.6 min), 0.9 mg/kg (43.1 +/- 10.8), and 1.2
      mg/kg (62.3 +/- 17.4 min) were significantly longer than were those for
      mivacurium (17.4 +/- 6.2 min). CONCLUSIONS: Mivacurium in a 0.25 mg/kg divided
      dose and rocuronium at 0.9 mg/kg and 1.2 mg/kg provide good or excellent
      intubation conditions at 90 s in most patients. Rocuronium was faster in onset at
      the higher doses (0.9 and 1.2 mg/kg) but had more prolonged recovery times to 25%
      single twitch height.

PMID- 9523812
TI  - Perioperative risk of bradyarrhythmias in patients with asymptomatic chronic
      bifascicular block or left bundle branch block: does an additional first-degree
      atrioventricular block make any difference?
AB  - BACKGROUND: The incidence of perioperative bradyarrhythmias in patients with
      bifascicular or left bundle branch block (LBBB) and the influence of an
      additional first-degree atrioventricular (A-V) block has not been evaluated with
      24-h Holter electrocardiographic monitoring. Therefore the authors assessed the
      rate of block progression and bradyarrhythmia in these patients. METHODS:
      Patients (n = 106) with asymptomatic bifascicular block or LBBB with or without
      an additional first-degree A-V block scheduled for surgery under general or
      regional anesthesia were enrolled prospectively. Three patients were excluded. Of
      the 103 remaining, 56 had a normal P-R interval and 47 had a prolonged one.
      Holter monitoring (CM2, CM5) was applied to each patient just before induction of
      anesthesia and was performed for 24 h. The primary endpoint of the study was the
      occurrence of block progression. As secondary endpoints, bradycardias < 40
      beats/min with hemodynamic compromise (systolic blood pressure < 90 mmHg) or
      asystoles > 5 s were defined. RESULTS: Block progression to second-degree A-V
      block and consecutive cardiac arrest occurred in one case of LBBB without a
      prolonged P-R interval Severe bradyarrhythmias with hypotension developed in
      another eight patients: asystoles > 5 s occurred in two cases and six patients
      had bradycardias < 40/min. Pharmacotherapy was successful in these eight
      patients. There was no significant difference for severe bradyarrhythmias
      associated with hemodynamic compromise between patients with and without P-R
      prolongation (P = 1.00). CONCLUSIONS: In patients with chronic bifascicular block
      or LBBB, perioperative progression to complete heart block is rare. However, the
      rate of bradyarrhythmias with hemodynamic compromise proved to be relevant.
      Because an additional first-degree A-V block did not increase the incidence of
      severe bradyarrhythmias and pharmacotherapy by itself was successful in nearly
      all cases, routine prophylactic insertion of a temporary pacemaker in such
      patients should be questioned.

PMID- 9523813
TI  - Patient-controlled epidural analgesia with bupivacaine and fentanyl on hospital
      wards: prospective experience with 1,030 surgical patients.
AB  - BACKGROUND: The efficacy and safety of patient-controlled epidural analgesia
      (PCEA) for postoperative analgesia on hospital wards was studied. METHODS:
      Postoperative analgesia was provided for 1,030 patients with PCEA using 0.05%
      bupivacaine and fentanyl, 4 microg/ml, in a standardized manner. Patients were
      seen at least twice a day by the staff of the anesthesia pain management service.
      Prospectively gathered data included verbal pain scores at rest and activity (0
      10); consumption of bupivacaine and fentanyl; and incidences of pruritus, nausea,
      sedation, hypotension, motor block, and respiratory depression. Descriptive
      statistics were used. Risk factors for side effects were determined using
      logistic regression. RESULTS: The study included 552 women and 477 men who
      underwent a median (mode) of 3 (2) days of PCEA. Their mean age was 59 +/- 16 yr
      and their mean weight was 76 +/- 19 kg. There were 454 abdominal, 165
      gynecologic, 126 urologic, 108 vascular, 90 thoracic, 83 orthopedic, and 4
      plastic surgical procedures. Median (mode) pain scores were 1 (0) at rest and 4
      (5) with activity on postoperative day 1. Incidences of side effects were 16.7%
      (pruritus), 14.8% (nausea), 13.2% (sedation), 6.8% (hypotension), 2% (motor
      block), and 0.3% (respiratory depression). Reasons for termination of PCEA were
      elective (82%), displaced epidural catheter (12%), anticoagulation (3%),
      infection (1%), side effects (1%), inadequate analgesia (1%), and other (<1%).
      Risk factors for side effects were female sex, patient weight <73 kg, patient age
      <58 yr, bupivacaine and fentanyl consumption >9 ml/h, use of analgesic adjuncts,
      and lumbar placement of epidural catheters. CONCLUSION: Patient-controlled
      epidural analgesia provides effective and safe postoperative analgesia on
      hospital wards.

PMID- 9523815
TI  - Stereoselective effects of etomidate optical isomers on gamma-aminobutyric acid
      type A receptors and animals.
AB  - BACKGROUND: The intravenous anesthetic etomidate is optically active and exists
      in two mirror-image enantiomeric forms. However, although the R(+) isomer is used
      as a clinical anesthetic, quantitative information on the relative potencies of
      the R(+) and S(-) isomers is lacking. These data could be used to test the
      relevance of putative molecular targets. METHODS: The anesthetic concentrations
      for a half-maximal effect (EC50) needed to induce a loss of righting reflex in
      tadpoles (Rana temporaria) were determined for both etomidate enantiomers. The
      effects of the isomers on gamma-aminobutyric acid (GABA)-induced currents in
      stably transfected mouse fibroblast cells was also investigated using the patch
      clamp technique. In addition, the effects of the isomers on a lipid chain-melting
      phase transition were determined. RESULTS: The EC50 concentrations for general
      anesthesia for the R(+) and S(-) isomers were 3.4 +/- 0.1 microM and 57 +/- 1
      microM, with slopes of n = 1.9 +/- 0.1 and n = 2.9 +/- 0.2, respectively. The
      R(+) isomer was also much more effective than the S(-) isomer at potentiating
      GABA-induced currents, although the degree of stereoselectivity varied with
      anesthetic concentration. R(+) etomidate potentiated the GABA-induced currents by
      increasing the apparent affinity of GABA for its receptor. Both isomers were
      equally effective at disrupting lipid bilayers. CONCLUSIONS: These data are
      consistent with the idea that the GABA(A) receptor plays a central role in the
      actions of etomidate. Etomidate exerts its effects on the receptor by binding
      directly to a specific site or sites on the protein and allosterically enhancing
      the apparent affinity of GABA for its receptor.

PMID- 9523814
TI  - Recovery of evoked potential amplitude after cerebral arterial air embolism in
      the rabbit: a comparison of the effect of cardiopulmonary bypass with normal
      circulation.
AB  - BACKGROUND: Cerebral arterial air embolism (CAAE) may cause neurologic injury
      during cardiac surgery. It is not known whether cardiopulmonary bypass (CPB)
      increases or decreases brain injury from CAAE compared with the normal
      circulation. METHODS: A model of CAAE was produced by injection of 50 microl/kg
      air into the internal carotid artery of methohexital-anesthetized New Zealand
      white rabbits. Somatosensory-evoked potential (SSEP) amplitude was measured
      serially as a marker of neurologic recovery. In experiment A, saline rather than
      air was injected to control for surgical manipulation and time in CPB (n = 4) and
      nonheparinized non-CPB (n = 4) animals. In experiment B, 50 microl/kg air was
      injected in CPB (n = 11) and nonheparinized non-CPB (n = 11) animals. In
      experiment C, non-CPB animals (n = 6) were given heparin according to the same
      protocol as for CPB. RESULTS: In experiment A, SSEP latencies and amplitudes did
      not differ between CPB and non-CPB conditions. In experiment B, there was no SSEP
      recovery 5 min after CAAE in either CPB or non-CPB animals. Thereafter, SSEP
      recovery was less in CPB animals than in non-CPB animals at 30 min (9 +/- 12% vs.
      29 +/- 20%; P = 0.009) and 60 min (18 +/- 15% vs. 39 +/- 22%; P = 0.030) after
      CAAE. Ninety-minute SSEP recovery did not differ between CPB and non-CPB groups
      (at 24 +/- 19% vs. 39 +/- 24%, respectively; P = 0.146). In experiment C
      (heparinized non-CPB), SSEP recovery 5, 30, 60, and 90 min after CAAE was 67 +/-
      48%, 72 +/- 47%, 80 +/- 35%, and 77 +/- 35%, respectively. CONCLUSIONS:
      Somatosensory-evoked potential recovery after CAAE is no better (and is probably
      worse) during CPB than during normal circulation. The adverse effect of CPB
      occurs despite heparinization, which, under non-CPB conditions, appears to be
      protective. Therapies in addition to heparin are needed during CPB to reduce
      neurologic injury from CAAE.

PMID- 9523816
TI  - Stereoselective differences in the vasorelaxing effects of S(+) and R(-) ketamine
      on rat isolated aorta.
AB  - BACKGROUND: S(+) ketamine, because of its higher anesthetic potency and lower
      risk of psychotomimetic reactions, has been suggested to be superior to presently
      available racemic ketamine. The racemate is a direct vasodilator in vivo, and
      thus the authors investigated the vasorelaxing effects of ketamine enantiomers on
      rat aorta. METHODS: Rat isolated aortic rings with and without endothelium were
      contracted with 3 x 10(-7) M norepinephrine. Then 10(-5) to 3 x 10(-3) M S(+), R(
      ), or racemic ketamine were added cumulatively. Vascular responses to ketamine
      were further studied in rings pretreated with the nitric oxide synthase inhibitor
      N(omega)-nitro-L-arginine (NNLA), the adenosine triphosphate-sensitive K+ channel
      antagonist glibenclamide, and the L-type calcium channel blocking agent D888.
      RESULTS: Ketamine enantiomers and the racemate produced concentration-dependent
      vasorelaxation. The relaxing effect of S(+) ketamine was significantly weaker
      compared with R(-) ketamine and the racemate reflected by the half-maximum
      effective concentration (EC50) values of 11.6 x 10(-4), 4.8 x 10(-4), and 6 x 10(
      4) M, respectively. Removal of the endothelium and NNLA or glibenclamide
      pretreatment did not significantly alter the vasorelaxing effect of ketamine. In
      contrast, D888 pretreatment significantly shifted the concentration-effect curves
      of both S(+) and R(-) ketamine rightward (EC50 values of 18.9 x 10(-4) and 8.5 x
      10(-4) M, respectively), whereas the difference between the isomers was not
      affected. CONCLUSIONS: Vasorelaxation by ketamine enantiomers is quantitatively
      stereoselective: The effect of S(+)ketamine is significantly weaker compared with
      that of the racemate and R(-) ketamine. This stereoselective difference is not
      due to nitric oxide release, activation of adenosine triphosphate-sensitive
      potassium channels, or differential inhibition of L-type calcium channels.

PMID- 9523817
TI  - Influence of acidosis on cardiotonic effects of milrinone.
AB  - BACKGROUND: The present study was designed to determine whether augmentation of
      cardiac performance by milrinone is affected by acidosis in in vivo canine and in
      vitro guinea pig preparations, and to elucidate a mechanism in relation to the
      cyclic adenosine monophosphate (cAMP) formation. METHODS: Halothane-anesthetized,
      ventilated dogs were randomly assigned to a control group (arterial pH [pHa]
      approximately 7.4, base excess [BE] > -2 mM; n = 7), mild acidosis group (pHa
      approximately 7.2, BE < -9 mM; n = 7); or severe acidosis group (pHa < 7, BE < 
      20 mM; n = 6). Arterial blood pressure, left ventricular pressure (including
      maximum rate of increase, LV dP/dtmax), and pulmonary blood flow (PBF) were
      measured. Acidosis was induced by transient hypoxia and maintained with hydrogen
      chloride infusion. Hemodynamic responses to milrinone infusions at 2 and 5 microg
      x kg(-1) x min(-1) were then studied. In addition, left atria and right
      ventricular strips were dissected from guinea pig hearts and suspended in HEPES
      Tyrode solution, with pH values adjusted to 7.4, 7, or 6.6. The concentration
      response relation of isometric contractions for milrinone (10(-7) to 10(-4) M)
      and 8-bromo-cAMP (10(-4) to 10(-3) M) were determined. RESULTS: In the control
      group of dogs, significant increases in LV dP/dtmax (2,674 +/- 822 to 3,999 +/-
      1,016 mmHg/s [means +/- SD]) and PBF (2.04 +/- 0.98 to 2.44 +/- 0.96 l/min [means
      +/- SD]) were seen with a milrinone infusion of 5 microg x kg(-1) x min(-1). In
      the mild acidosis group, 5 microg x kg(-1) x min(-1) milrinone also increased LV
      dP/dtmax and PBF. However, neither LV dP/dtmax nor PBF changed in the severe
      acidosis group. In in vitro experiments, milrinone exerted a positive inotropic
      effect in a concentration-dependent manner on the right ventricular preparations
      at pH 7.4, but not at pH 7 and 6.6, whereas no significant difference was
      observed in inotropic responses to 8-bromo-cAMP at pH values of 6.6, 7, and 7.4
      on the right ventricular strips. In the right ventricular in vitro preparation,
      10(-4) M milrinone was accompanied by a significant increase in intracellular
      cAMP content at apH of 7.4 but not 7. CONCLUSIONS: These results indicate that
      the inotropic effect of milrinone is attenuated by acidosis due, at least in
      part, to decreased cAMP formation in acidotic muscle.

PMID- 9523818
TI  - Is calcium a coronary vasoconstrictor in vivo?
AB  - BACKGROUND: Calcium produces constriction in isolated coronary vessels and in the
      coronary circulation of isolated hearts, but the importance of this mechanism in
      vivo remains controversial. METHODS: The left anterior descending coronary
      arteries of 20 anesthetized dogs whose chests had been opened were perfused at 80
      mmHg. Myocardial segmental shortening was measured with ultrasonic crystals and
      coronary blood flow with a Doppler flow transducer. The coronary arteriovenous
      oxygen difference was determined and used to calculate myocardial oxygen
      consumption and the myocardial oxygen extraction ratio. The myocardial oxygen
      extraction ratio served as an index of effectiveness of metabolic vasodilation.
      Data were obtained during intracoronary infusions of CaCl2 (5, 10, and 15 mg/min)
      and compared with those during intracoronary infusions of dobutamine (2.5, 5.0,
      and 10.0 microg/min). RESULTS: CaCl2 caused dose-dependent increases in segmental
      shortening, accompanied by proportional increases in myocardial oxygen
      consumption. Although CaCl2 also increased coronary blood flow, these increases
      were less than proportional to those in myocardial oxygen consumption, and
      therefore the myocardial oxygen extraction ratio increased. Dobutamine caused
      dose-dependent increases in segmental shortening and myocardial oxygen
      consumption that were similar in magnitude to those caused by CaCl2. In contrast
      to CaCl2, however, the accompanying increases in coronary blood flow were
      proportional to the increases in myocardial oxygen consumption, with the result
      that the myocardial oxygen extraction ratio remained constant. CONCLUSIONS:
      Calcium has a coronary vasoconstricting effect and a positive inotropic effect in
      vivo. This vasoconstricting effect impairs coupling of coronary blood flow to the
      augmented myocardial oxygen demand by metabolic vascular control mechanisms.
      Dobutamine is an inotropic agent with no apparent direct action on coronary
      resistance vessels in vivo.

PMID- 9523819
TI  - Neuromuscular relaxants as antagonists for M2 and M3 muscarinic receptors.
AB  - BACKGROUND: Neuromuscular relaxants such as pancuronium bind to M2 and M3
      muscarinic receptors as antagonists. Blockade of muscarinic receptors in atria of
      the M2 subtype mediates tachycardia. In the lung, blockade of M2 receptors on
      parasympathetic nerves potentiates vagally induced bronchospasm, whereas blockade
      of M3 receptors on bronchial smooth muscle inhibits bronchospasm. The current
      study was designed to quantify the affinity of a series of neuromuscular
      relaxants for the M2 and M3 muscarinic receptors, which were individually stably
      transfected in Chinese hamster ovary cell lines. METHODS: Competitive radioligand
      binding assays determined the relative binding affinities of the neuromuscular
      relaxants pancuronium, succinylcholine, mivacurium, doxacurium, atracurium,
      rocuronium, gallamine, and pipecuronium for the muscarinic receptor in the
      presence of a muscarinic receptor antagonist (3H-QNB) in membranes prepared from
      cells individually expressing either the M2 or M3 muscarinic receptor. RESULTS:
      All muscle relaxants evaluated displaced 3H-QNB from muscarinic receptors. The
      relative order of potency for the M2 muscarinic receptor (highest to lowest) was
      pancuronium, gallamine, rocuronium, atracurium, pipecuronium, doxacurium,
      mivacurium, and succinylcholine. The relative order of potency for the M3
      muscarinic receptor (highest to lowest) was pancuronium, atracurium,
      pipecuronium, rocuronium, mivacurium, gallamine, succinylcholine, and doxacurium.
      CONCLUSIONS: All neuromuscular relaxants studied had affinities for the M2 and M3
      muscarinic receptor, but only pancuronium and gallamine had affinities within the
      range of concentrations achieved with clinical use. The high affinities of
      gallamine and pancuronium for the M2 muscarinic receptor are consistent with a
      mechanism of M2 receptor blockade in relaxant-induced tachycardia.

PMID- 9523820
TI  - Halothane and isoflurane decrease alveolar epithelial fluid clearance in rats.
AB  - BACKGROUND: Active sodium transport is the primary mechanism that drives alveolar
      fluid clearance. In the current study, the effects of exposure to halothane and
      isoflurane on alveolar fluid clearance in rats were evaluated. METHODS: Rats were
      exposed to either halothane (0.4% for 6 h or 2% for 2 h) or isoflurane (0.6% for
      6 h or 2.8% for 2 h). Reversibility of halothane effects was assessed after 2 h
      of exposure to 2% halothane. Alveolar and lung liquid clearance were measured by
      intratracheal instillation of a 5% albumin solution with 1.5 microCi of 125I
      albumin, during mechanical ventilation with 100% FiO2 and the halogenated agent.
      The effect of terbutaline (10(-4) M) added to the albumin solution was tested
      after 2 h of exposure to 2% halothane. The increase in protein concentration in
      the airspaces over 1 h was used to evaluate alveolar liquid clearance. Lung
      liquid clearance was calculated gravimetrically. RESULTS: Alveolar liquid
      clearance rates were decreased by 24%, 30% and 40% compared with controls (P <
      0.05) after 2 h of exposure to halothane, 6 h of exposure to halothane, and 6 h
      of exposure to isoflurane, respectively. After 2 h of exposure to isoflurane,
      alveolar liquid clearance did not change. In the 2-h halothane exposure group,
      alveolar liquid clearance returned to the control value 2 h after withdrawal of
      halothane. Terbutaline increased alveolar liquid clearance by 50% and 89% in the
      control and 2-h halothane exposure groups, respectively. In all experiments, the
      same results were obtained for alveolar and lung liquid clearance. CONCLUSIONS:
      Halothane and isoflurane caused a reversible decrease in alveolar epithelial
      fluid clearance. Two hours of exposure to halothane did not alter the stimulatory
      effect of terbutaline on alveolar liquid clearance.

PMID- 9523821
TI  - Hypoxia causes apnea during epidural anesthesia in rabbits.
AB  - BACKGROUND: Although pulmonary function is minimally changed by neuraxial
      blockade in most cases, ventilatory arrest may ensue in rare cases. The authors
      examined the mechanism of apnea in a rabbit model of sudden ventilatory arrest
      during the combination of epidural anesthesia and hypoxia. METHODS: Rabbits were
      studied during alpha-chloralose sedation and spontaneous ventilation through a
      tracheostomy tube. Heart rate and mean arterial pressure were monitored by
      intraarterial cannulation. Respiratory rate and tidal volume were measured by
      pneumotachograph. Responses were recorded during administration of oxygen at
      inspired oxygen concentrations of 11% for 2.5 min and 0% for 40 s, before and
      after either thoracolumbar epidural blockade (0.4 ml/kg lidocaine, 1.5%) or
      intramuscular lidocaine (15 mg/kg). In a third group of animals, epinephrine was
      given intravenously during epidural blockade to return mean arterial pressure to
      baseline values before hypoxia. In a fourth group of animals, which did not get
      lidocaine, sympathetic blockade and hypotension were produced with intravenously
      administered trimethaphan rather than epidural blockade. RESULTS: Thoracolumbar
      epidural anesthesia decreased mean arterial pressure from 76 +/- 4 mmHg (mean +/-
      SE) to 42 +/- 2 mmHg. Apnea during hypoxia occurred in 90% of these animals (nine
      of ten) but in only 11% of animals (one of nine) after intramuscularly
      administered lidocaine (P < 0.01). Treatment of epidural hypotension with
      epinephrine prevented apnea (zero of nine animals). Apnea during hypoxia occurred
      in 50% (three of six) of animals given trimethaphan. Apnea in all groups was
      sudden in onset, with no preceding decreases in respiratory rate or tidal volume.
      CONCLUSIONS: Epidural anesthesia results in a narrowed margin of safety for
      oxygen delivery to the brain and predisposes subjects to ventilatory arrest
      during hypoxia. This results from the combined effects of decreased blood oxygen
      content, which is due to decreased inspired oxygen concentration superimposed on
      circulatory depression due to neural blockade.

PMID- 9523822
TI  - Ketamine inhibits monoamine transporters expressed in human embryonic kidney 293
      cells.
AB  - BACKGROUND: Ketamine has been characterized as having psychotomimetic and
      sympathomimetic effects. These symptoms have raised the possibility that ketamine
      affects monoaminergic neurotransmission. To elucidate the relation between
      ketamine and monoamine transporters, the authors constructed three cell lines
      that stably express the norepinephrine, dopamine, and serotonin transporters and
      investigated the effects of ketamine on these transporters. METHODS: Human
      embryonic kidney cells were transfected using the Chen-Okayama method with the
      human norepinephrine, rat dopamine, and rat serotonin transporter cDNA subcloned
      into the eukaryotic expression vector. Using cells stably expressing these
      transporters, the authors investigated the effects of ketamine on the uptake of
      these compounds and compared them with those of pentobarbital. RESULTS:
      Inhibition analysis showed that ketamine significantly inhibited the uptake of
      all three monoamine transporters in a dose-dependent manner. The Ki (inhibition
      constant) values of ketamine on the norepinephrine, dopamine, and serotonin
      transporters were 66.8 microM, 62.9 microM, and 162 microM, respectively.
      Pentobarbital, a typical general anesthetic agent with no psychotic symptoms, did
      not affect the uptake of monoamines, however. Further, neither the glycine
      transporter 1 nor the glutamate/aspartate transporter was affected by ketamine,
      indicating that ketamine preferentially inhibits monoamine transporters.
      CONCLUSIONS: Ketamine inhibited monoamine transporters expressed in human
      embryonic kidney cells in a dose-dependent manner. This result suggests that the
      ketamine-induced inhibition of monoamine transporters might contribute to its
      psychotomimetic and sympathomimetic effects through potentiating monoaminergic
      neurotransmission.

PMID- 9523823
TI  - Anesthesia sensitivity in mice that lack the beta3 subunit of the gamma
      aminobutyric acid type A receptor.
AB  - BACKGROUND: The mammalian gamma-aminobutyric acid type A (GABA(A)) receptor, a
      likely target of anesthetic action, exhibits remarkable subunit heterogeneity. In
      vitro expression studies suggest that there is subunit specificity to anesthetic
      responses at the GABA(A) receptor. The authors tested whether genetically
      engineered mice that lack the beta3 subunit of the GABA(A) receptor differed in
      their sensitivities to several general anesthetic agents. METHODS: Median
      effective concentrations for loss-of-righting reflex and tail clamp/withdrawal
      for enflurane and halothane were determined in mice with and without the beta3
      gene and gene product. Sleep time was measured after intraperitoneal injection of
      pentobarbital, ethanol, etomidate, and midazolam. RESULTS: Null allele mice
      (beta3 -/-) did not differ from wild-type mice (beta3 +/+) in the obtunding
      response to enflurane and halothane but were significantly more resistant to
      enflurane (null allele half-effect concentrations [EC50] of 2.59 +/- 0.10 vs.
      wild-type EC50 of 2.06 +/- 0.12 atm %, P < 0.001) and halothane (null allele EC50
      of 1.73 +/- 0.04 vs. wild-type EC50 of 1.59 +/- 0.05 atm %, P = 0.01) as
      determined by tail clamp response. Wild-type and null allele mice exhibited
      divergent responses to other sedative agents active at the GABA(A) receptor. No
      differences were noted in sleep times after administration of pentobarbital and
      ethanol, but null allele mice were more resistant to etomidate (null allele EC50
      of 17.8 +/- 1.9 min vs. wild-type EC50 of 26.2 +/- 2.4 min, P < 0.02) and
      midazolam (null allele EC50 of 14.2 +/- 7.8 min vs. wild-type EC50 of 41.3 +/-
      10.4 min, P < 0.05). CONCLUSIONS: The beta3 subunit of the GABA(A) receptor
      appears to be important in the mediation of the immobilizing (tail clamp) but not
      obtunding (loss-of-righting reflex) effects of the volatile anesthetic agents
      enflurane and halothane. These data support the hypotheses that separate
      components of the anesthetic state are mediated via different central nervous
      system loci; that the GABA(A) receptor is a likely target for the immobilizing
      response to volatile anesthetic agents; and that the beta3 subunit plays a direct
      or indirect role in the mediation of this response. Absence of the beta3 subunit
      appears to attenuate the obtunding effect of midazolam and etomidate but appears
      not to alter the obtunding effect of pentobarbital, enflurane, and halothane,
      suggesting that these anesthetic agents produce hypnosis by different specific
      molecular mechanisms.

PMID- 9523824
TI  - Propofol and ketamine only inhibit intracellular Ca2+ transients and contraction
      in rat ventricular myocytes at supraclinical concentrations.
AB  - BACKGROUND: The cellular mechanisms that mediate the cardiodepressant effects of
      intravenous anesthetic agents remain undefined. The objective of this study was
      to elucidate the direct effects of propofol and ketamine on cardiac excitation
      contraction coupling by simultaneously measuring intracellular calcium
      concentration ([Ca2+]i) and shortening in individual, field-stimulated
      ventricular myocytes. METHODS: Freshly isolated rat ventricular myocytes were
      loaded with the Ca2+ indicator, fura-2, and placed on the stage of an inverted
      fluorescence microscope in a temperature-regulated bath. [Ca2+]i and myocyte
      shortening (video edge detection) were monitored simultaneously in individual
      cells that were field-stimulated at 0.3 Hz. RESULTS: Baseline [Ca2+]i (mean +/-
      SEM) was 80 +/- 12 nM, and resting cell length was 112 +/- 2 microm. Field
      stimulation increased [Ca2+]i to 350 +/- 23 nM, and the myocytes shortened by 10%
      of diastolic cell length. Both intravenous anesthetic agents caused dose
      dependent decreases in peak [Ca2+]i and shortening. At 300 microM, propofol
      prolonged time to peak concentration and time to 50% recovery for [Ca2+]i and
      shortening. In contrast, changes in time to peak concentration and time to 50%
      recovery in response to ketamine were observed only at the highest
      concentrations. Neither agent altered the amount of Ca2+ released from
      intracellular stores in response to caffeine. Propofol but not ketamine, however,
      caused a leftward shift in the dose-response curve to extracellular Ca2+ for
      shortening, with no concomitant effect on peak [Ca2+]i. CONCLUSIONS: These
      results indicate that both intravenous anesthetic agents have a direct negative
      inotropic effect, which is mediated by a decrease in the availability of [Ca2+]i.
      Propofol but not ketamine may also alter sarcoplasmic reticulum Ca2+ handling and
      increase myofilament Ca2+ sensitivity. The effects of propofol and ketamine are
      primarily apparent at supraclinical concentrations, however.

PMID- 9523826
TI  - Availability of anesthesia personnel in rural Washington and Montana.

PMID- 9523825
TI  - Benzodiazepines differentially inhibit phenylephrine-induced calcium oscillations
      in pulmonary artery smooth muscle cells.
AB  - BACKGROUND: Modulation of intracellular free calcium is a critical determinant of
      vasomotor tone. The authors investigated the effects of three benzodiazepines on
      alpha-adrenergic-induced oscillations in intracellular free calcium in individual
      pulmonary artery smooth muscle cells. METHODS: Pulmonary artery smooth muscle
      cells were cultured from explants of canine intrapulmonary artery. Fura-2-loaded
      pulmonary artery smooth muscle cells were continuously superfused with
      phenylephrine (10 microM) at 37 degrees C on the stage of an inverted
      fluorescence microscope. Intracellular free calcium was measured using a dual
      wavelength spectrofluorometer. After establishment of steady-state intracellular
      free calcium oscillations induced by phenylephrine, lorazepam, diazepam, or
      midazolam was added to the superfusate. The amplitude and frequency of the
      intracellular free calcium oscillations were compared before and after addition
      of each agent. RESULTS: Resting mean +/- SEM values of intracellular free calcium
      were 68 +/- 8 nM. Phenylephrine stimulated dose-dependent oscillations in
      intracellular free calcium, which reached a peak concentration of 676 +/- 35 nM
      and a frequency of 1.08 +/- 0.1 transients/min. Addition of lorazepam (1 microM)
      inhibited (P < 0.05) the amplitude (591 +/- 32 nM) but not the frequency (0.97 +/
      0.1 transients/min) of the oscillations. Conversely, diazepam (1 microM)
      decreased (P < 0.05) the frequency (0.79 +/- 0.1 transients/min) but not the
      amplitude (663 +/- 37 nM) of the oscillations. These effects were dose-dependent.
      In contrast, midazolam (1-30 microM) had no effect on the amplitude or frequency
      of intracellular free calcium oscillations. At concentrations higher than 100
      microM, however, all three benzodiazepines inhibited both the amplitude and
      frequency of the intracellular free calcium oscillations. CONCLUSION: Lorazepam
      and diazepam but not midazolam exerted differential inhibitory effects on
      phenylephrine-induced intracellular free calcium oscillations. Benzodiazepines
      may alter the pulmonary vascular response to sympathetic alpha-adrenoreceptor
      activation by direct inhibition of intracellular free calcium signaling in
      pulmonary artery smooth muscle cells.

PMID- 9523827
TI  - Health-care report cards and implications for anesthesia.

PMID- 9523828
TI  - Methohexital as alternative to propofol for intravenous anesthesia in children
      undergoing daily radiation treatment: a case report.

PMID- 9523829
TI  - Intravenous regional phenoxybenzamine in the treatment of reflex sympathetic
      dystrophy.

PMID- 9523830
TI  - Coronary revascularization without cardiopulmonary bypass: use of ischemic
      preconditioning and adenosine.

PMID- 9523831
TI  - Unintended supraventricular tachycardia induced by extracorporeal shock wave
      lithotripsy.

PMID- 9523832
TI  - A technique for population pharmacodynamic analysis of concentration-binary
      response data.

PMID- 9523833
TI  - Cost savings in the operating room.

PMID- 9523834
TI  - Efficacy of tracheal gas insufflation during expiration in reducing PaCO2.

PMID- 9523835
TI  - Expiratory washout in patients with severe acute respiratory distress syndrome.

PMID- 9523836
TI  - The use of brachial plexus block for venous catheterization in low and very low
      birthweight infants.

PMID- 9523837
TI  - A better, safer, and inexpensive way to open glass ampules.

PMID- 9523838
TI  - Central venous access via the distal femoral vein using ultrasound guidance.

PMID- 9523839
TI  - Rapid intercellular transfer of GPI-anchored CD4.

PMID- 9523840
TI  - Abnormal cholesterol biosynthesis produced by AY 9944 in the rat leads to
      skeletal deformities similar to the Smith-Lemli-Opitz syndrome.

PMID- 9523841
TI  - The Th1/Th2 paradigm in allergic bronchopulmonary aspergillosis.

PMID- 9523842
TI  - Rationale for immune-based therapies for HIV-1 infection.

PMID- 9523843
TI  - Hypoxia-inducible factor 1 and the molecular physiology of oxygen homeostasis.

PMID- 9523844
TI  - Variegated transfer of recombinant glycosylphosphatidylinositol-anchored CD4
      among cultured cells: correlation of flow cytometric and microscopic
      observations.
AB  - Glycosylphosphatidylinositol-anchored proteins (GPI-proteins) expressed on the
      outer leaflet of cell membranes are involved in diverse physiologic as well as
      pathologic processes in humans. Previously, we demonstrated the intercellular
      transfer of overexpressed CD4-GPI in vitro from transduced HeLa cells to their
      parental cell line. In this report we present further information on the transfer
      process and the nature of the transferred GPI-proteins. In mixed-cell
      populations, the transfer of CD4-GPI was detectable within minutes at levels
      proportional to the ratio of donor and recipient cells. The amount of CD4-GPI
      detected with flow cytometry on the surface of the recipient cells varied
      according to cell type. Microscopy of mixed cell populations revealed discrete
      CD4-GPI containing aggregates on the target cells, whereas colocalized transfer
      of cytoplasm was not detected. Separation of cocultivated cells by semipermeable
      membranes largely prevented CD4-GPI transfer, but aggregates containing CD4-GPI
      were demonstrated by electron microscopy in supernatants passed through filters
      of 0.4-mm pore size.

PMID- 9523845
TI  - Abnormal cholesterol biosynthesis as in Smith-Lemli-Opitz syndrome disrupts
      normal skeletal development in the rat.
AB  - Smith-Lemli-Opitz syndrome (SLOS) in human infants is a common autosomal
      recessive malformation syndrome (estimated incidence, 1:20,000). It is
      characterized clinically by congenital anomalies, especially craniofacial and
      limb defects, and biochemically by a defect in 7-dehydrocholesterol-delta7
      reductase activity (7DHC-reductase), the final enzyme in cholesterol
      biosynthesis. In previous studies, early administration of the 7DHC-reductase
      inhibitor AY9944 to pregnant rats resulted in a high frequency of
      holoprosencephaly, relevant to craniofacial anomalies of SLOS. In order to test
      the effect of AY9944 on limb development, we treated dams on gestation day 7
      (GD7), which delays the biochemical defect to about GD13 to GD14. Sera were
      sampled on GD12, GD14, and GD21 and cholesterol and dehydrocholesterols (7DHC and
      8DHC) were measured by gas-chromatography-mass spectrometry (GC-MS), as for the
      diagnosis of SLOS. GD21 fetuses were examined for gross malformations and
      skeletal development. In treated dams, the SLOS biochemical marker 7DHC accounted
      for one fourth and one third of total sterols, respectively, on GD12 and GD14,
      and cholesterolemia on these two gestation days was reduced by 50% and 43%,
      respectively, as compared with control values. This maternal metabolic defect was
      associated with decrease in fetal weight and delayed ossification. In addition,
      scapular malformations were observed in four fetuses from three litters. The
      malformations could have been caused by the same mechanism as holoprosencephaly
      after early treatment with AY9944. These cholesterol-deficiency-based
      malformations could have a common cause in the abnormal expression of Hedgehog or
      other developmental gene proteins, and may thus explain various congenital
      polymalformative syndromes in humans, including SLOS.

PMID- 9523846
TI  - IgE down regulation and cytokine induction by Aspergillus antigens in human
      allergic bronchopulmonary aspergillosis.
AB  - Allergic bronchopulmonary aspergillosis (ABPA), occurring primarily in patients
      with asthma or cystic fibrosis (CF), is a hypersensitivity reaction to
      Aspergillus fumigatus (Af), and is characterized by increased serum IgE levels
      and peripheral blood and pulmonary eosinophilia. We evaluated the IgE and
      cytokine profile in ABPA through enzyme-linked immunosorbent assay (ELISA), and
      evaluated eosinophil activity with the eosinophil peroxidase (EPO) assay. IgE and
      cytokines were measured in supernatants from cultures of peripheral blood
      mononuclear cells (PBMC) from three subject groups: ABPA patients, patients with
      asthma, and healthy individuals. All cultures for the three subject groups were
      studied in the presence and absence of two purified Af antigens (the 35-kD
      antigen and heat shock protein 1). We found that increased in vitro levels of IgE
      in unstimulated PBMC culture supernatants correlated significantly with serum IgE
      concentrations in ABPA patients. We measured a decrease in IgE levels of up to
      75% of baseline values in supernatants from PBMC cultured with Af antigens.
      Interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) concentrations in cultures
      with Af were increased in ABPA, whereas concentrations of IL-4 did not differ in
      the three subject groups. An inverse relation was noted between the changes in
      IgE and IFN-gamma measured in 4 of 5 ABPA patients. The PBMC supernatants also
      promoted EPO activity in purified eosinophils from ABPA patients, and to a lesser
      extent in purified eosinophils from healthy subjects. These results show that the
      35-kD antigen and HSP1 from Af downregulate IgE in vitro but are capable of
      inducing eosinophilia in ABPA. Further studies could result in the
      characterization of epitopes leading to these disparate effects. An
      identification of the IgE-down-regulating epitopes in Af antigens might have
      therapeutic significance.

PMID- 9523847
TI  - Prolonged decreases in plasma nitrate levels at early postoperative phase after
      hepato-pancreato-biliary surgery.
AB  - Nitric oxide (.NO) is known to influence circulatory, neural, immunologic, and
      metabolic alterations. To evaluate the clinical significance of .NO production
      under surgical stress, serial measurements of plasma nitrite plus nitrate levels
      were performed in 45 surgical patients. Group A included 19 patients who
      underwent major surgery with uneventful postoperative courses. Group B included
      18 patients who underwent laparoscopic cholecystectomy. Group C included 8
      patients whose surgery was complicated by intra-abdominal abscesses. Eight
      healthy volunteers served as controls. Plasma nitrate levels were determined with
      a redox chemiluminescence .NO analyzer and coincided with measurements made by
      high-performance liquid chromatography (r = 0.868, p < 0.0001, 58 samples).
      During laparotomy, arterial nitrate levels correlated well with peripheral,
      portal, and hepatic venous nitrate levels (r = 0.966, 0.938, and 0.949,
      respectively; p < 0.0001). A significant decrease in nitrate from preoperative
      levels in groups A (postoperative day (POD) 1 and 3; p < 0.0005) and B (POD 1, p
      < 0.0001) was observed; nitrate levels in group C did not decrease for 14 days
      after surgery. Plasma nitrate levels in groups A and B were significantly
      different (POD 1 through 6, p < 0.05) and at POD 3 were significantly lower in
      group A (p < 0.005). Plasma nitrate levels measured before and after fasting or
      food intake were not significantly different. These results suggest that surgical
      stress leads to a decrease in the end product of .NO in the whole body, and that
      the greater the surgical stress the longer the duration of decreased .NO
      production.

PMID- 9523849
TI  - Use of proliferating cell nuclear antigen as a marker of liver regeneration after
      partial hepatectomy in rats.
AB  - In order to document and compare proliferating cell nuclear antigen (PCNA) mRNA
      and protein levels with more traditional parameters of hepatic regenerative
      activity in a rat model, adult male Sprague-Dawley rats (4 to 6 per group) were
      killed at various times up to 96 hours after 70% partial hepatectomy. At each
      time interval, tissue PCNA mRNA abundance and protein levels were documented (by
      Northern and Western blot analysis, respectively) and compared with the results
      of PCNA immunostaining and 3H-thymidine incorporation into hepatic DNA. Tissue
      PCNA protein levels were also documented in additional groups of rats 12, 24, 36,
      and 48 hours after sham or 30% partial hepatectomy. PCNA mRNA expression after
      partial hepatectomy was variable: almost undetectable at 24 hours, levels
      returned to baseline at 36 hours, then fell again to low levels at 96 hours. PCNA
      protein levels remained stable for 36 hours, increased to fourfold above baseline
      (p < 0.01) at 48 hours, then remained elevated for the duration of the 96-hour
      study. Changes in PCNA by immunostaining were similar but tended to occur
      somewhat earlier (significant increases being detectable at 24 hours), whereas 3H
      thymidine incorporation detected the earliest increases in DNA synthesis at 12
      hours and peaked at 36 hours. Peak PCNA protein levels correlated with the extent
      (0%, 30%, or 70%) of hepatic resection. The results indicate that PCNA protein
      level as determined by Western blot analysis, but not PCNA mRNA expression,
      correlates with PCNA immunostaining and 3H-thymidine incorporation in the
      regenerating liver. These findings support the use of PCNA protein determinations
      as an additional quantitative measure of hepatic regenerative activity after
      partial hepatectomy in rats.

PMID- 9523848
TI  - Prevalence of antiphospholipid antibodies in patients with chronic liver disease
      related to alcohol or hepatitis C virus: correlation with liver injury.
AB  - Antiphospholipid antibodies (APAs) have been reported in various clinical
      conditions. However, the pathogenesis and clinical significance of these
      antibodies are still unclear. The objective of this study was to assess the
      prevalence of APAs in patients with chronic alcohol- or hepatitis C virus (HCV)
      related liver disease and to evaluate their relation to the underlying liver
      disease. We prospectively studied 201 patients referred to an hepato
      gastroenterology department, including 77 patients with a history of alcohol
      abuse (group I) and 124 with chronic HCV infection (group II), and 107 healthy
      subjects (control population). Liver biopsy was performed in all patients. In
      cirrhotic patients, the severity of the liver disease was assessed with the use
      of Child's classification, as modified by Pugh. Several biologic parameters,
      including lupus anticoagulant and anticardiolipin antibodies, were determined.
      Forty-eight percent of patients in group I and 33% of those in group II had APAs.
      Among cirrhotic patients, APAs were more frequent in patients with Child grade B
      or C than in those with grade A severity. In patients with chronic HCV-related
      liver disease, a correlation was found between APA levels and liver fibrosis (P =
      0.009); no relation was found between APA levels and histologic liver disease
      activity (P = 0.25). In the control group, one subject was APA-positive. None had
      lupus anticoagulant. APAs seem to be frequently associated with chronic liver
      disease of various causes. These results suggest further investigations on the
      potential role of these antibodies in fibrosis or liver injury.

PMID- 9523850
TI  - Value of methylprednisolone in prevention of the arthralgia-myalgia syndrome
      associated with the total dose infusion of iron dextran: a double blind
      randomized trial.
AB  - The safety and efficacy of total dose infusion (TDI) of iron dextran has been
      well documented. In 40% of treated patients, an arthralgia-myalgia syndrome
      develops. The purpose of this randomized, double-blind, prospective study was to
      investigate whether intravenous (i.v.) administration of methylprednisolone (MP)
      prevents this complication. Sixty-five patients, 34 women and 31 men, ages 36 to
      80 years, received either normal saline before and after TDI (group 1), 125 mg
      i.v. MP before and saline after TDI (group 2), or 125 mg i.v. MP before and after
      TDI (group 3). Patients were observed for 72 hours and reactions were recorded
      and graded according to severity. Fifty-eight percent of group 1 patients, 33% of
      group 2, and 26% of group 3 had reactions to TDI. The severity of reactions
      (minimal, mild, and moderate, respectively) was as follows: group 1--6, 6, and 2;
      group 2--1, 5, and 0; group 3--5, 1, and 0. Data were analyzed by the two-sided
      Fisher's exact test using 95% confidence intervals with the approximation of
      Woolf. These data demonstrate that administration of MP before and after TDI
      reduces the frequency and severity of the arthralgia-myalgia syndrome. We
      conclude that 125 mg i.v. MP should be given routinely before and after TDI of
      iron dextran.

PMID- 9523851
TI  - Interleukin-1 increases expression of the LYT-10 (NFkappaB2) proto
      oncogene/transcription factor in renal cell carcinoma lines.
AB  - The LYT-10 gene was initially cloned by virtue of its disruption by the
      translocation breakpoint in some t(10;14) lymphoid neoplasms. LYT-10 is now known
      to encode a component of the NF-kappaB family of transcriptional activators and
      has therefore also been designated NFkappaB2. Activation of NF-kappaB is
      generally associated with its transfer to the nucleus and is followed by a rapid
      increase in expression of its target genes, which include cytokines such as
      interleukin-6 (IL-6). IL-6 can also be induced by other transcription factors
      such as NF-IL6. We studied the interaction of IL-1 and these transcription
      factors in two renal cell carcinoma cell lines (ACHN and Caki-1). These lines
      produce high levels of IL-6, show endogenous chloramphenicol acetyltransferase
      activity for the IL-6 promoter, and have high basal levels of transcripts
      encoding the NF-kappaB components Lyt-10, p50, and p65 as well as the NF-IL6
      transcription factor. IL-1alpha and IL-1beta markedly increased steady-state
      levels of LYT-10 (NFkappaB2) transcripts and nuclear Lyt-10 protein in both cell
      lines. Levels of the NFkappaB1 (p50-encoding), p65, and NF-IL6 transcripts also
      increased after IL-1 exposure. These changes were accompanied by a 20-fold or
      greater increase in levels of IL-6 messenger ribonucleic acid (mRNA) and protein.
      Our observations suggest that the mechanism by which IL-1alpha or IL-1beta
      induces IL-6 may be mediated through increases in LYT-10 mRNA and protein levels
      as well as increases in expression of other transcription factors (NFkappaB1,
      p65, and NF-IL6), in addition to the known ability of IL-1 to post
      translationally activate NF-kappaB.

PMID- 9523852
TI  - Haptotactic and growth stimulatory effects of fibrin(ogen) and thrombin on
      cultured fibroblasts.
AB  - We tested the ability of purified, ultraviolet C virally inactivated components
      of human fibrin sealant (FS) to modulate the chemotaxis, adherence, and
      proliferation of cultured cells. A fibrin clot formed on a near-confluent layer
      of human fibroblasts (HFs) recruited cells from the surrounding area. Thrombin
      (Thr) enhanced HF proliferation by a factor of 1.5 to 1.8, whereas fibrinogen
      (Fib) exerted only a minimal proliferative effect. We developed a new cell
      haptotactic/attachment assay by using Thr and Fib covalently bound to Sepharose
      beads (SBs). The kinetics of cell binding were approximately equivalent for beads
      coated with either protein. Uncoated SBs or fibrinogen-bound SBs (Fib-SB)
      pretreated with plasmin did not attract HFs. AlphaThr-SB induced a positive
      migratory response that was not affected by blocking its proteolytic site,
      whereas gammaThr-SB elicited no response. X irradiation of HFs at a dose of 6 Gy
      showed that the migratory response of HF is independent of proliferation, as
      confirmed by a bromodeoxyuridine uptake assay. Several types of cultured cells
      (murine fibroblasts, smooth muscle cells, aortic endothelial cells, and murine
      mammary carcinoma cells) also attached to Fib-SB. By contrast, human
      keratinocytes, human ovarian carcinoma cells, murine macrophage-like cells,
      leukemic cells, and murine mast cells did not attach. Our results provide some
      mechanistic insights into the haptotactic and proliferative effects of Fib and
      Thr on different cells.

PMID- 9523853
TI  - Utility of a nitric oxide electrode for monitoring the administration of nitric
      oxide in biologic systems.
AB  - Amperometric techniques for the detection of nitric oxide (NO) are commercially
      available, but their sensitivity and specificity are not well described. We
      evaluated the sensitivity and specificity of a Clark-style, platinum NO
      electrode. The electrode has a lower limit of detection for NO of <25 pmol/ml in
      vitro and is linear over the range from 25 pmol/ml to 4 nmol/ml. The electrode is
      specific for NO so long as the protective membrane that covers the electrode is
      intact. Any defect in this membrane results in the detection of other redox
      agents such as hydrogen peroxide. Because of its ease of handling, specificity,
      and sensitivity, the NO electrode is a useful tool for quantification of
      administered NO in vitro and in various biologic systems.

PMID- 9523854
TI  - Transfer of surface markers.

PMID- 9523855
TI  - Lack of inhibitory effect of octreotide on intestinal adaptation in short bowel
      syndrome in the rat.
AB  - BACKGROUND: Octreotide is a long-acting analogue of somatostatin, which is
      effective in the treatment of secretory diarrhea in a number of disorders
      including short bowel syndrome. Its use in this syndrome has been limited because
      of concerns about potential adverse effect on intestinal adaptation, because it
      inhibits a number of trophic hormones. This study was conducted to determine
      whether octreotide inhibits intestinal adaptation in a rat model of short bowel
      syndrome. METHODS: Thirty male Sprague-Dawley rats were divided into four
      treatment groups, eight receiving 80% small-bowel resection and treated with 2.25
      microg/kg(-1) per day(-1) of octreotide, eight receiving 80% small-bowel
      resection and treated with 25 microg/kg(-1) per day(-1) of octreotide, eight
      receiving 80% small-bowel resection with saline control, and six receiving sham
      operation with saline control. Mucosal weight, protein, and sucrase levels were
      subsequently analyzed after 2 weeks of therapy. RESULTS: Massive adaptation
      occurred in all three groups relative to sham-operated controls. However, neither
      the pharmacologic nor the much higher dose of octreotide demonstrated any adverse
      effects on intestinal adaptation. CONCLUSION: In our animal model, octreotide
      does not inhibit intestinal adaptation after massive small-bowel resection.

PMID- 9523856
TI  - Disturbances in biotin metabolism in children undergoing long-term anticonvulsant
      therapy.
AB  - BACKGROUND: In subjects undergoing long-term therapy with carbamazepine and/or
      phenytoin, reduced plasma concentrations of biotin have been reported. However,
      the diagnostic value of plasma biotin is unclear, in part because of the presence
      of significant plasma concentrations of biotin metabolites. Pathologic organic
      aciduria has also been reported with long-term anticonvulsant therapy, suggesting
      biotin deficiency, but no mechanism leading to deficiency has yet been
      determined. METHODS: In the current study, we sought to determine whether biotin
      catabolism was accelerated in children receiving long-term treatment with certain
      anticonvulsants and to assess biotin status as judged by urinary excretion of
      biotin and 3-hydroxyisovaleric acid, an organic acid that is an indicator of
      deficiency of a biotin-dependent enzyme. Seven children treated with
      carbamazepine and/or phenytoin and six treated with phenobarbital provided
      untimed urine samples. Sixteen healthy children receiving no anticonvulsants
      served as controls. Biotin and biotin metabolites were determined by high
      performance liquid chromatography/avidin-binding assay. Urinary excretion of 3
      hydroxyisovaleric acid was determined using gas chromatography/mass spectrometry.
      RESULTS: Bisnorbiotin excretion was increased significantly in the
      carbamazepine/phenytoin group and in the phenobarbital group. Biotin sulfoxide
      excretion was significantly increased in the carbamazepine/phenytoin group but
      not in the phenobarbital group. 3-Hydroxyisovaleric acid excretion was increased
      significantly in the carbamazepine/phenytoin group. However, only one child
      (carbamazepine/phenytoin group) had a decreased urinary excretion of biotin.
      CONCLUSION: These data provide evidence that long-term administration of some
      anticonvulsants can accelerate biotin catabolism, but the indicators of biotin
      status conflict.

PMID- 9523857
TI  - Copper in infant nutrition: safety of World Health Organization provisional
      guideline value for copper content of drinking water.
AB  - BACKGROUND: Copper is an essential nutrient for humans. Recently, a limit of
      31.48 micromol/l (2 mg/l) was proposed by the World Health Organization as the
      provisional guideline value for copper content of drinking water. The objective
      of the study was to determine the tolerance of chronic exposure to drinking water
      with low or high copper content in infants. METHODS: Healthy infants (n = 128)
      were randomly assigned to receive drinking water with less than 1.57 micromol/l
      (<0.1 mg/l) (n = 48) or 31.48 micromol/l (2 mg/l) of copper (n = 80) from 3 to 12
      months of age. At 6, 9, and 12 months of age, serum concentrations of copper,
      ceruloplasmin, and superoxide dismutase; erythrocyte metallothionein; bilirubin;
      transaminases; and gamma-glutamyl transferase were measured. RESULTS: Small
      differences in biochemical indexes of copper nutrition were observed between the
      groups, but there was no evidence of adverse or toxic effects. These findings may
      be explained by an adaptive response to the higher copper intake, limiting copper
      absorption, and increasing biliary secretion, as well as by an increase in copper
      storage. It is also possible that the sensitivity of the biochemical indicators
      employed to detect differences in copper status is limited. CONCLUSION: No acute
      or chronic adverse consequences of consuming water with copper content of 31.48
      micromol/l (2 mg/l) were detected in infants during the first year of life. The
      results support the safety of the World Health Organization's provisional
      guideline value for copper in drinking water during infancy.

PMID- 9523858
TI  - Discrepancies between males and females with cystic fibrosis in dietary intake
      and pancreatic enzyme use.
AB  - BACKGROUND: Length of survival of females with cystic fibrosis is worse than it
      is in males. Results of current research have shown an important correlation
      among dietary intake, nutritional status, lung function, and survival. The
      purpose of this study was to explore gender differences in dietary intake and
      pancreatic enzyme replacement therapy in males and females with cystic fibrosis.
      METHODS: The study was a cross-sectional measurement of clinical characteristics,
      energy, and fat intakes in males and females attending the cystic fibrosis
      outpatients clinics of the John Hunter Hospital, Newcastle, Australia. Twenty
      nine subjects, (17 females and 12 males), completed 4-day weighed food records to
      measure total energy intake and the contribution of macronutrients and to
      document use of pancreatic enzyme replacement therapy. Energy intake was assessed
      as the percentage of the recommended energy intake for age and sex. RESULTS:
      Females with cystic fibrosis had significantly lower energy and fat intakes than
      males, whereas the females used significantly more pancreatic enzyme replacement
      therapy. There were no significant differences in clinical characteristics
      between groups. CONCLUSION: The results support the possibility that gender
      differences in the energy and fat intakes of older patients may contribute to
      differential median survival time of males and females with cystic fibrosis.

PMID- 9523859
TI  - Glutathione peroxidase is not a functional marker of selenium status in the
      neonatal period.
AB  - BACKGROUND: The antioxidant enzyme glutathione peroxidase is a selenoprotein
      that, in adults with low selenium intakes, has a strong linear relationship with
      blood selenium and hence is used as a functional indicator of selenium status.
      Our aim was to evaluate glutathione peroxidase as a functional marker of selenium
      status in preterm infants. METHODS: Erythrocyte glutathione peroxidase activity
      and plasma and erythrocyte selenium were measured between days 1-5 and then
      weekly until discharge in 63 preterm infants with mean +/- standard error birth
      weight and gestation of 1572+/-60g and 30.7+/-0.3 weeks. A healthy reference
      group of term infants (n = 46) was assessed at day 5 and at 6 weeks. RESULTS: In
      preterm infants, over the first 3 months, the association of glutathione
      peroxidase activity with erythrocyte selenium was weak and inconsistent and
      nonexistent with selenium intake or plasma selenium. No correlations between any
      of these indicators were evident for term infants. In preterm infants, plasma and
      erythrocyte selenium declined over the first 6 weeks (p < 0.01), while
      glutathione peroxidase activity increased (p < 0.05). In term infants, plasma
      selenium increased (p < 0.001), but there was no change in erythrocyte selenium
      or glutathione peroxidase activity. For preterm infants, glutathione peroxidase
      activities at weeks 4 and 6 were associated with maximum inspired oxygen
      concentration, ventilator pressure, and days of ventilation. CONCLUSIONS: This
      data is consistent with animal and in vitro evidence that glutathione peroxidase
      may be confounded by oxygen. We conclude that erythrocyte glutathione peroxidase
      activity is not a reliable functional marker of preterm selenium status in the
      neonatal period.

PMID- 9523860
TI  - Gastroesophageal reflux and Nissen fundoplication following percutaneous
      endoscopic gastrostomy in children.
AB  - BACKGROUND: Abnormal gastroesophageal reflux after percutaneous endoscopic
      gastrostomy is a serious problem in neurologically impaired children. Protective
      fundoplication has been advocated. Whether esophageal pH monitoring before
      percutaneous endoscopic gastrostomy will predict later problems with
      gastroesophageal reflux is unclear. METHODS: Eighty-five mostly neurologically
      impaired pediatric patients who underwent percutaneous endoscopic gastrostomy
      were studied retrospectively regarding complications, success of nutritional
      rehabilitation, and the incidence of pathologic gastroesophageal reflux. Follow
      up period was 1 to 4 years. Twenty-four-hour esophageal pH monitoring was
      performed in 46 patients before percutaneous endoscopic gastrostomy. RESULTS:
      There were no deaths. Two major complications occurred that required surgical
      intervention, and 14 minor complications occurred related to the procedure. Z
      scores for weight increased significantly after percutaneous endoscopic
      gastrostomy. pH probe results were normal in 22 patients (group 1). Five required
      medical treatment for gastroesophageal reflux after percutaneous endoscopic
      gastrostomy, but only 1 (5%) later required Nissen fundoplication. pH probe
      results were abnormal in 24 patients (group 2). Nineteen required medical therapy
      for gastroesophageal reflux, and 7 (29%) later needed fundoplication (p < 0.05,
      incidence of fundoplication group 1 vs. group 2). Improvement in Z-scores was
      similar in patients requiring and not requiring fundoplication. CONCLUSIONS:
      Percutaneous endoscopic gastrostomy is a safe and effective technique for long
      term nutritional support in children. Abnormal gastroesophageal reflux is common.
      Normal findings in an esophageal pH study before percutaneous endoscopic
      gastrostomy may be predictive of a favorable outcome with respect to
      gastroesophageal reflux. This is in contrast to patients with abnormal results in
      pH studies before percutaneous endoscopic gastrostomy of whom a relatively large
      percentage may later require fundoplication. Improved nutritional status after
      percutaneous endoscopic gastrostomy does not appear to have an impact on the
      severity of gastroesophageal reflux.

PMID- 9523861
TI  - Aluminum in total parenteral nutrition solutions produces portal inflammation in
      rats.
AB  - BACKGROUND: Aluminum contaminates parenteral nutrition solutions and accumulates
      in bone and liver of patients receiving total parenteral nutrition therapy.
      Although previous reports have shown that parenteral administration of aluminum
      in pharmacologic doses to rats results in the production of elevated total serum
      bile acid concentrations alone or in combination with decreased bile flow, they
      have failed to demonstrate any abnormalities in the histologic appearance of
      liver tissue. The effects of aluminum in total parenteral nutrition and of
      aluminum chloride on total serum bile acid concentrations, aluminum contents of
      the liver, and histopathologic changes in the liver were studied in rats.
      METHODS: The aluminum concentrations in the aluminum chloride solution and total
      parenteral nutrition formula were equal (300 microg/l). They were given
      intraperitoneally as follows: control group, 0.9% saline for 14 days; T7 group,
      total parenteral nutrition for 7 days; A7 group, aluminum chloride for 7 days;
      A14 group, aluminum chloride for 14 days; T7A7 group, total parenteral nutrition
      for 7 days and aluminum chloride for the next 7 days; and T7O7 group, total
      parenteral nutrition for 7 days and 0.9% saline for the next 7 days. Volumes of
      0.9% saline, aluminum chloride, and total parenteral nutrition given to rats were
      equal. During the experiment, rats were maintained on rat chow and water ad
      libitum. Serum glutamic oxaloacetic transaminase, serum glutamic pyruvic
      transaminase, alkaline phosphatase, and bile acid concentrations and aluminum
      content of the liver were measured. The liver was evaluated histopathologically
      by light microscope, and a morphologic portal inflammation index was calculated.
      RESULTS: Portal inflammation was present in all groups except the control group.
      The morphologic portal inflammation correlated with hepatic aluminum accumulation
      in all groups and was the highest in the T7A7 group. Levels of serum glutamic
      oxaloacetic transaminase, serum glutamic pyruvic transaminase, and alkaline
      phosphatase did not correlate with the histopathologic findings, but serum bile
      acid concentrations correlated with morphologic portal inflammation and hepatic
      aluminum accumulation in all groups. Hepatic aluminum accumulation also
      correlated with the duration of exposure to total parenteral nutrition and
      aluminum chloride concentration. CONCLUSION: Aluminum in contaminating doses, not
      in pharmacologic doses, accumulates in the liver and can produce hepatobiliary
      dysfunction characterized by portal inflammation detectable in histologic
      examination of liver tissue.

PMID- 9523862
TI  - Intestinal absorption of ursodeoxycholic acid in children and adolescents with
      inflammatory bowel disease.
AB  - BACKGROUND: Ursodeoxycholic acid absorption in the proximal intestine may be
      impaired in patients with inflammatory bowel disease. METHODS: We examined the
      intestinal absorption of ursodeoxycholic acid by the oral ursodeoxycholic acid
      tolerance test in 19 children and adolescents with inflammatory bowel disease at
      various stages, including 8 patients with unoperated Crohn's disease, 3 patients
      with ileal-resected Crohn's disease, 8 with ulcerative colitis, and 8 healthy
      control subjects. RESULTS: Ursodeoxycholic acid malabsorption was present in all
      patients with unoperated Crohn's disease in the first diagnosed active stage, in
      3 of 5 patients in a relapsing active stage, and in 2 of 8 patients in remission.
      Ursodeoxycholic acid absorption was significantly lower in patients in the first
      diagnosed active stage than in the healthy controls (p < 0.01) or in patients in
      remission (p < 0.01). There was no significant difference between healthy
      controls and the patients in a relapsing active stage or in remission.
      Ursodeoxycholic acid absorption was abnormal during the first postoperative month
      in patients with ileal-resected Crohn's disease, but normalized over time.
      Malabsorption of ursodeoxycholic acid was not observed in any patients with
      ulcerative colitis. CONCLUSIONS: These findings suggest that absorption of
      ursodeoxycholic acid in the proximal intestine is impaired in patients with
      Crohn's disease and that the oral ursodeoxycholic acid tolerance test is a
      convenient and useful means of evaluating the absorption of bile acid in the
      proximal intestine in pediatric patients with ileal or ileocolic Crohn's disease.

PMID- 9523863
TI  - Lack of correlation between genotype and phenotype in celiac disease.
AB  - BACKGROUND: Celiac disease has a wide range of clinical features. The goal of
      this study was to evaluate whether specific HLA genotypes are associated with
      particular clinical appearances. METHODS: One hundred forty-five patients with
      confirmed celiac disease were oligotyped for DR and DQ HLA genes. Clinical notes,
      physical examination, and a questionnaire provided their personal data. Patients
      were grouped into nine genotypic categories, according to the presence of the
      specific DQ heterodimer DQA1*0501-DQB1*0201 (hence termed alpha0beta0), in single
      or double dose, and the presence of the DRB4 antigen. RESULTS: Age at first
      symptoms and age at beginning of gluten-free diet were not significantly
      different in the nine groups. The initial symptoms of the disease had a similar
      distribution in all groups. In twenty-seven patients, disease was diagnosed by
      family screening: they shared a similar HLA genotype with those who had relevant
      symptoms. The actual growth status-evaluated by standardized height, percentage
      of median weight for age, and percentage of median weight for height--was not
      different in the nine groups. Presence of unusual health complaints was not
      associated with a specific genotype. CONCLUSIONS: There is no evidence that
      clinical features of celiac disease are associated with different HLA genotypes.
      Genes outside the HLA may play a relevant role.

PMID- 9523864
TI  - The 13carbon urea breath test for the noninvasive detection of Helicobacter
      pylori in children: comparison with culture and determination of minimum analysis
      requirements.
AB  - BACKGROUND: The purpose of the study was to determine the accuracy of the
      labelled 13carbon urea breath test for the diagnosis of Helicobacter pylori in
      children and to simplify the 13carbon urea breath test in identifying the most
      discriminating sampling time. METHODS: H. pylori was searched for in 100 children
      aged 10.5+/-4.5 years by histology, bacteriological counts, and culture on antral
      biopsies together with serology and 13carbon urea breath test. Breath samples
      were obtained before ingestion (T0) of 75 mg urea-13C and every 10 minutes after
      until T60. 13CO2 excess ratio was measured by isotope ratio mass spectrometry,
      and values expressed as delta per mil over baseline enrichment (delta 13CO2). The
      arithmetic mean (Mdelta 13CO2) of T20 to T60 values was calculated and the test
      considered positive with Mdelta 3CO2 higher than Mdelta 13CO2 + 3 SD as
      determined in noninfected children. RESULTS: Mdelta 13CO2 of noninfected children
      as assessed by culture was 1.4+/-0.6 per mil, determining a positive cut-off
      value of 3.44 per mil. Mdelta 13CO2 was correlated in 11 children with biopsy
      bacteriological counts. Both culture and 13carbon urea breath test were positive
      in 38 of 100 children, without any discordance. Plotting 13carbon urea breath
      test results at each sampling time versus Mdelta 13CO2 showed weaker correlations
      at T20, T30, T50, and T60, than at T40. The two-sample method at T0 and T30, T40,
      T50, had high sensitivity and specificity. Single-sample analysis obtained at T40
      gave a comparable sensitivity and a slightly reduced specificity. CONCLUSION:
      13carbon urea breath test is sensitive and specific in children. Two samples
      collected at T0 and T40 provide the most discriminating procedure.

PMID- 9523865
TI  - Protein and amino acid metabolism in three- to twelve-month-old infants fed human
      milk or formulas with varying protein concentrations.
AB  - BACKGROUND: The metabolic response to different protein intakes from breast milk
      and/or formulas varying in protein concentrations, in combination with
      supplementary foods, has not been studied in infants who are in the second half
      of infancy. METHODS: Healthy infants, exclusively breast-fed until 3 months old,
      were randomly assigned to one of three groups, F13, F15, or F18, and were given
      formulas with 13, 15, or 18 g/l of protein, respectively. Infants breast-fed (B)
      and mixed-fed (M) (breast milk and formula) at 6 months formed the fourth and
      fifth groups. All infants received the same supplementary foods and were studied
      from ages 3 to 12 months. RESULTS: The concentrations of albumin, prealbumin, and
      transferrin were similar in all groups. At 6 months, serum and urine urea
      concentrations were lower in B and M, compared with urea levels in the formula
      fed groups of infants. At 12 months, urine urea was lower in B + M than it was in
      F18. At 6 months, plasma concentrations of phenylalanine, tyrosine, and
      methionine were higher in all formula-fed groups; and those of valine.
      isoleucine, and threonine were higher in F18 and F15 than they were in B and M.
      Plasma concentrations of methionine, valine, and threonine were higher in F18
      than in F13. At 12 months, plasma levels of tyrosine, methionine, valine,
      isoleucine, and leucine were higher in F18 than they were in B + M. CONCLUSION:
      Many indexes of protein metabolism were similar in groups F13, B, and M,
      particularly at 6 months. In contrast, the provision of a formula with 18 g/l of
      protein resulted in a different metabolic pattern, which could indicate
      unnecessarily high protein intakes.

PMID- 9523866
TI  - Peptide excretion in celiac disease.
AB  - BACKGROUND: In celiac disease, the mucosa in the small intestine is damaged. This
      study was conducted to determine whether the normal peptide and protein uptake
      from the gut is increased in patients with celiac disease. METHODS: The low
      molecular-weight peptides were measured in urine from children and adults with
      untreated celiac disease. A reversed-phase technique was used. RESULTS: The
      excretion of peptides increased compared with that in an age- and sex-matched
      reference group. CONCLUSIONS: Celiac patients have hyperpeptiduria. It is
      possible that some of these peptides are bioactive and may mediate varying
      systemic effects also found in untreated celiac disease.

PMID- 9523867
TI  - Growth of prepubertal children with inflammatory bowel disease.
AB  - BACKGROUND: Growth retardation has been reported in children with chronic
      inflammatory bowel disease, especially in those with Crohn's disease. Most of
      these studies concern adolescent patients. METHODS: The growth of 47 prepubertal
      children (20 boys and 27 girls, mean age at diagnosis 7 years) with inflammatory
      bowel disease was studied at Tampere University Hospital, Department of
      Paediatrics. The mean height and height velocity standard deviation scores were
      calculated at diagnosis and, after that, yearly. The cumulative doses of oral and
      rectal prednisone per year were calculated. The severity of the disease was
      scored. The statistical analysis was carried out using the analysis of variance
      for repeated measurements. RESULTS: During the year preceding the diagnosis,
      children with inflammatory bowel disease had grown more slowly than their healthy
      peers. At diagnosis, they were slightly shorter as a group than are healthy
      children. During treatment and follow-up the mean height velocity of children
      with inflammatory bowel disease increased (change in the mean height velocity
      standard deviation scores from -0.84 to +1.08), normalizing the mean heights of
      these children compared with those of their healthy peers (change in the mean
      height standard deviation scores from -0.32 to +0.05). In the analysis of
      covariance, the poorest growth was seen in children with Crohn's disease, scored
      as severe, and the best growth in children with mild ulcerative colitis. No
      difference was seen in groups with or without prednisone treatment. CONCLUSIONS:
      Growth retardation is an important sign of chronic inflammatory bowel disease in
      prepubertal as well as adolescent children. During treatment, increasing growth
      velocity brings these children as a group to normal heights for age and sex.

PMID- 9523868
TI  - Acute pancreatitis after orthotopic liver transplantation in children: incidence,
      contributing factors, and outcome.
AB  - BACKGROUND: Acute pancreatitis after orthotopic liver transplantation is a well
      known complication in adults that has never been described in children. In
      adults, end-stage liver disease related to hepatitis B, intraoperative pancreatic
      injury caused by extensive peripancreatic dissection, the type of biliary
      anastomosis performed, and numerous drugs, have all been described as
      predisposing factors in acute pancreatitis after liver transplantation. The
      current retrospective review was undertaken to identify the incidence, the
      contributing factors, and the outcome of acute pancreatitis after liver
      transplantation in children. METHODS: During a 10-year period, 375 children
      underwent 434 liver transplantations in the authors' institution. In seven
      patients (1.9%), clinical acute pancreatitis developed after orthotopic liver
      transplantation. Indication for initial liver transplantation was biliary atresia
      (n = 3), acute liver failure (n = 3), and type 1 Crigler-Najjar syndrome. In all
      seven patients, liver graft function was initially adequate. The diagnosis of
      acute pancreatitis was based on clinical, biochemical, ultrasonographic, and
      surgical signs. RESULTS: In six patients, acute pancreatitis appeared within the
      first week after transplantation. The diagnosis was confirmed by abdominal
      laparotomy in five children. In the current series, emergency liver
      transplantation (p < 0.001), retransplantations (p < 0.001), and infectious
      peritonitis (p < 0.001) were contributing factors. Despite supportive measures,
      three patients died (43%) because of multiple organ dysfunction syndrome.
      CONCLUSIONS: Acute pancreatitis is an uncommon but life-threatening complication
      after liver transplantation in children. Early diagnosis and aggressive treatment
      of infectious complications are major elements in the management of acute
      pancreatitis after liver transplantation.

PMID- 9523869
TI  - Clinical quiz. Gastric volvulus in a large paraesophageal hiatal hernia.

PMID- 9523870
TI  - The biology of inherited disorders of the gastrointestinal tract part I:
      gastrointestinal disorders.

PMID- 9523871
TI  - Aspects of sugar transport relevant to oral rehydration therapy.

PMID- 9523872
TI  - Metastatic cutaneous Crohn's disease in a child.

PMID- 9523873
TI  - Chronic diarrhea with massive intestinal plasma cell infiltration and high
      polyclonal immunoglobulin A serum level.

PMID- 9523874
TI  - Comment on the vitamin E content in infant formulas, follow-on formulas, and
      formulas for low birth weight infants. ESPGHAN Committee on Nutrition. European
      Society of Pediatric Gastroenterology, Hepatology and Nutrition.

PMID- 9523875
TI  - Mesenchymal hamartoma of the liver: failed management by marsupialization.

PMID- 9523876
TI  - Use of octreotide for the treatment of severe gastrointestinal bleeding in
      children.

PMID- 9523877
TI  - New, improved Helicobacter pylori eradication therapy in children.

PMID- 9523878
TI  - Genes in the development of the pancreas.

PMID- 9523879
TI  - Requirements for training to ensure competence of endoscopists performing
      invasive procedures in children.

PMID- 9523880
TI  - Laparoscopic esophagomyotomy as treatment for achalasia.

PMID- 9523881
TI  - Recurrence of Crohn's disease.

PMID- 9523883
TI  - Endoscopic diagnosis of duodenal stenosis.

PMID- 9523882
TI  - H. pylori infection and gastritis.

PMID- 9523884
TI  - Cyclical vomiting syndrome.

PMID- 9523885
TI  - 40- and 70-kHz vocalizations of mice (Mus musculus) during copulation.
AB  - Ultrasonic vocalizations were tape recorded from five pairs of copulating mice
      and subjected to spectrographic analysis. As expected, the mice emitted numerous
      70-kHz vocalizations. At the beginning of the test, before copulation began, 70
      kHz calls were emitted almost continuously, while calls with lower spectrographic
      frequencies were not observed. Subsequently, bursts of 70-kHz calling generally
      began shortly before mounts and intromissions and persisted until dismount.
      Intermixed with these 70-kHz calls were additional vocalizations of about 40 kHz.
      Calling rates were highest just prior to intromission. Once intromissions began,
      70-kHz calls continued at a lower rate until dismount; however, 40-kHz calls
      occurred infrequently. In a second experiment, the male was found to emit the
      majority of the 70-kHz calls and all of the 40-kHz calls. When the male was
      devocalized, few calls were detected, regardless of whether the female was able
      to call. If the male was not devocalized, high rates of calling were detected,
      even if the female was devocalized.

PMID- 9523886
TI  - Effects of housing conditions and 5-HT2A activation on male rat sexual behavior.
AB  - Adult male rats were housed individually or in groups for a period of 39 days. In
      Experiment 1, the effects of housing conditions on sexual behavior and concurrent
      spontaneous "wet dog shaking" (WDS) were investigated. Individual housing
      significantly impaired male sexual behavior and resulted in a trend toward
      increased WDS. In Experiment 2, the effects of housing conditions were examined
      following administration of the serotonergic type 2A (5-HT2A) agonist DOI.
      Individual housing significantly increased DOI-induced WDS. The implications of
      these findings are discussed in the context of stress-induced corticosterone
      secretion and the possible regulatory effect on 5-HT2A receptors.

PMID- 9523887
TI  - Separation of septal influences on lordosis, ultrasound production, and body
      weight.
AB  - Previous results suggest that septal fibers inhibit lordosis, ultrasound
      production, and bodily growth (rate of weight gain) in female hamsters. To
      determine if the systems responsible for these effects can be dissociated, septal
      connections with or through the preoptic area (POA) were disrupted by horizontal
      cuts across the interface between these areas. Some subjects received cuts that
      were centered medially and extended across most of the interface. Others received
      cuts that were offset laterally and disrupted just the lateral half of this
      region. Each response was affected by at least one of these cuts. However, the
      patterns of effects differed across measures. Lordosis was facilitated equally by
      medial and lateral cuts, suggesting its dependence on fibers that are
      concentrated where the cuts overlapped, i.e., laterally along the septal-POA
      interface. In contrast, ultrasound rate was increased just by the more medial
      cuts, suggesting its dependence on relatively medial fibers. Finally, body weight
      was increased by both lesions but consistently responded more to the more medial
      cuts. This suggests that the relevant fibers are distributed across much of the
      septal-POA interface but are concentrated in its medial half. Taken together,
      these results suggest that septal connections affecting lordosis, ultrasound
      production, and body weight follow different trajectories as they enter or leave
      the ventral septum. In turn, this strengthens the case for the mediation of these
      effects by distinct populations of septal cells.

PMID- 9523888
TI  - Presence of cues from stressed conspecifics increases reactivity to aversive
      events in cattle: evidence for the existence of alarm substances in urine.
AB  - In gregarious species like cattle, the presence of partners often affects fear
      related reactions. The first experiment investigated whether behavioral and
      physiological responses to stress depend on the emotional state of the partner.
      Aubrac heifers were presented with food in a novel environment. Compared to
      heifers in the presence of a companion that had been previously habituated to the
      environment without receiving shocks, those in the presence of a companion animal
      that had previously received electric shocks in that environment had a stronger
      increase of cortisol response (11.2+/-1.1 vs. 7.4+/-0.9 ng/mL), showed a
      significantly longer latency to feed (60.1+/-12.3 vs. 17.8+/-5.9 s), and fed more
      slowly (54.5+/-11.4 vs. 110+/-7.3 s). After repeated exposure to the test
      conditions, when heifers of both treatments fed rapidly after entrance, response
      to an unexpected air blast from the feeding bucket was measured. Heifers in the
      presence of a stressed companion showed an increased latency to feed again
      compared to those with a nonstressed companion (44.5+/-5.1 vs. 22.8+/-4.3 s).
      Stressed companions urinated during tests; therefore the second experiment
      investigated whether heifers respond differently to urine collected from stressed
      and nonstressed conspecifics. In a first test, heifers were presented with food
      on a grid in a bucket in a novel environment. They had a longer latency to feed
      when the bucket contained urine from stressed rather than from nonstressed
      conspecifics underneath the grid (128.1+/-9.6 vs. 108.2+/-4.9 s). In a second
      test, heifers were presented with a novel object in a familiar environment.
      Heifers showed a longer latency to explore the object when it had been sprayed
      with urine from stressed compared to urine from nonstressed conspecifics (215.2+/
      45.0 vs. 25.8+/-8.6 s). The results show that heifers perceive the state of
      increased stress of conspecifics and become more fearful as a result. They
      further show that this perception is at least partly mediated by olfactory cues
      in the urine.

PMID- 9523889
TI  - An automated training device for pattern discrimination learning of group-housed
      gerbils.
AB  - The setup, designed for the rodent Meriones unguiculatus (gerbil), allows
      flexible stimulus presentations and rewarding as well as on-line data
      registration. It consists of a spacious housing where the animals have free
      access to water. Food is supplied exclusively in the y-maze training compartment
      and serves as a reinforcer in an operant conditioning paradigm.

PMID- 9523890
TI  - The rat's acceptance and preference for sucrose, maltodextrin, and saccharin
      solutions and mixtures.
AB  - Prior work indicates that rats prefer a mixture of sucrose and maltodextrin to
      either carbohydrate alone. The present experiment examined whether a sucrose +
      maltodextrin (S + M) mixture also increases total fluid intake as does saccharin
      + carbohydrate mixtures. In 23 h/day, one-bottle tests male rats consumed more of
      a 1% sucrose + 1% maltodextrin mixture than they did of either 2% sucrose or 2%
      maltodextrin. Adding 0.2% saccharin to the S + M mixture further stimulated
      consumption. The rats overconsumed the mixture solutions primarily by increasing
      bout size. In two-bottle choice tests the rats strongly preferred the S + M
      mixture to the 2% sucrose and 2% maltodextrin solutions and showed a nonreliable
      preference for the S + M + saccharin mixture to the S + M mixture. The
      palatability of the S + M mixture is thought to be related to the activation of
      separate "sweet" and "maltodextrin" tastes.

PMID- 9523891
TI  - c-fos-like immunoreactivity in the subfornical organ and nucleus of the solitary
      tract following salt intake by sodium-depleted rats.
AB  - Acute sodium depletion by furosemide induces a robust salt appetite in the rat
      which is satiated rapidly by ingestion of sodium chloride (salt) solutions. To
      identify neuronal populations activated by sodium depletion and by salt intake,
      we quantified c-fos-like immunoreactivity (c-FLI) in the subfornical organ (SFO)
      and nucleus of the solitary tract (NTS) after sodium depletion and at time
      intervals from 30 min to 12 h after 1 h of access to 0.3 M NaCl. Rats drank 10+/
      1.6 mL over 1 h, with most of the intake occurring by 30 min. Increased numbers
      of c-FLI-positive cells were observed in the SFO 24 h after sodium depletion; c
      FLI remained elevated for 90 min after 0.3 M NaCl intake and then declined until
      the number of c-FLI-positive cells at 12 h was not significantly different from
      mock-depleted levels. Sodium depletion alone did not significantly elevate c-FLI
      in the NTS, but the number of c-FLI-positive nuclei in the NTS was significantly
      increased after 0.3 M NaCl intake. The cellular location and temporal pattern of
      c-FLI expression are consistent with activation of neural circuitry sensitive to
      humoral, gustatory, and postingestive stimuli accompanying sodium depletion and
      0.3 M NaCl ingestion. c-FLI in the SFO and NTS may serve as quantifiable markers
      in the central nervous system of the state of sodium depletion and of ingestive
      (orosensory and gastrointestinal) sensory stimulation, respectively.

PMID- 9523892
TI  - Double-vein jugular/inferior vena cava clamp technique for long-term in vivo
      studies in rats.
AB  - We present a step-by-step manual for chronic cannulation of rats using a simple
      technique. This concept facilitates repeated clamping of the same rat over a 6-10
      week period, providing a completely separate infusion route from blood sampling
      access which is placed into mixed venous blood in the inferior vena cava.
      Permanent catheters implanted into the left external jugular vein and the
      inferior vena cava were used for miniature blood sampling and recycling. The
      design and running of clamp experiments and other physiological research models
      are detailed. Long-term reliable venous access, simple installation, and easy
      after-care of the rats' cannulas are the principal advantages of the procedure
      described.

PMID- 9523893
TI  - Body temperature and behavior of tree shrews and flying squirrels in a thermal
      gradient.
AB  - The daily rhythms of body temperature, temperature selection, and locomotor
      activity of tree shrews and flying squirrels were studied in a thermal gradient.
      In accordance with previous observations in other mammalian species, the rhythm
      of temperature selection was found to be 180 degrees out of phase with the body
      temperature rhythm in both species. Comparison of the amplitude of the body
      temperature rhythm in the presence and absence of the ambient temperature
      gradient indicated that behavioral temperature selection reduces the amplitude of
      the body temperature rhythm. This provides support for the hypothesis that the
      homeostatic control of body temperature opposes-rather than facilitates-the
      circadian oscillation in body temperature.

PMID- 9523894
TI  - Galanin injection into the nucleus of the solitary tract stimulates feeding in
      rats with lesions of the paraventricular nucleus of the hypothalamus.
AB  - Feeding can be stimulated by injection of galanin into the area postrema/nucleus
      of the solitary tract (AP/NTS) or fourth ventricle (4V). However, the threshold
      for galanin-induced feeding is lower when galanin is injected into the
      paraventricular nucleus of the hypothalamus (PVN) than when injected into the
      NTS. The greater apparent sensitivity of the PVN to galanin and the proximity of
      this nucleus to the third ventricle raise the possibility that galanin injected
      into the AP/NTS or 4V may stimulate feeding by accessing receptors in the PVN
      rather than by a local action in the hindbrain. To assess this possibility,
      feeding in response to NTS galanin was evaluated in rats with bilateral
      electrolytic lesions of the PVN. We found that PVN lesions did not abolish
      feeding induced by injections of galanin into the NTS. Rather, galanin-induced
      feeding, but not mercaptoacetate- or 2-deoxy-D-glucose-induced feeding, was
      significantly enhanced in PVN-lesioned rats compared to sham-operated controls.
      These results suggest that galanin receptors in the NTS region mediate feeding in
      response to galanin and that the galaninergic nerve terminals innervating these
      receptors may originate in part from cell bodies in the PVN.

PMID- 9523895
TI  - Effect of maternal deprivation on N-acetyltransferase activity rhythm in blinded
      rat pups.
AB  - It has been reported that the rhythms of infant rats synchronize with the
      mother's rhythm until the light-dark cycle comes and has strong effects on their
      endogenous clocks. We found that periodic maternal deprivation (PMD) was able to
      cause a phase shift of serotonin N-acetyltransferase (NAT) in neonatal blinded
      rat pups. PMD in which contact with the mother was allowed for only 4 h caused a
      phase shift of NAT rhythm, irrespective of the timing of contact with the mother
      in a day. Acute single mother deprivation caused an excess of NAT activity for
      more hours than usual and contact with the mother prevented such an excessive
      response. Mother deprivation may act as a cold stress, since artificial warming
      of pups gave the same results as contact with the mother. When the pups were
      artificially warmed by a heater during a 1-week deprivation period, a flat 24-h
      pattern of NAT was observed. The mechanism causing a phase shift of NAT activity
      rhythm of rat pups may be complicated.

PMID- 9523896
TI  - Induced preference or conditioned aversion for sodium chloride in rats with
      chronic bile duct ligation.
AB  - We examined whether a learned aversion to saline could account for the reduction
      in saline intake produced by bile duct ligation (BDL) in rats and whether
      increased saline intake by BDL rats was associated with hypotension. In three
      experiments, rats were given continuous access to water in choice with saline
      after surgery. In Experiment 1, rats were deprived of food and fluid for 24 h and
      then given 2-h access to either 0.15 or 0.3 M saline. Rats received a BDL or sham
      ligation immediately (paired) or 48 h after (nonpaired) the 2-h bout of saline
      ingestion. The results show that nonpaired BDL rats increased their daily saline
      intake relative to nonpaired sham-ligated or paired BDL rats approximately 1-4
      weeks after surgery. In Experiment 2, when water and either cherry or grape Kool
      Aid (0.05% w/v) dissolved in 0.15 M saline to distinguish the flavor of the
      solution was offered prior to surgery, BDL rats reduced their ingestion of grape
      flavored saline after surgery regardless of whether they were exposed to grape-
      or cherry-flavored saline prior to surgery. In Experiment 3, when rats were
      offered water and 0.3 M saline 48 h after surgery, BDL rats ligated for 4 weeks
      increased their saline intake relative to sham-ligated controls and this
      elevation in saline intake by BDL rats was associated with hypotension. The
      results suggest that the symptoms associated with the BDL surgery can serve as
      effective unconditioned stimuli in the acquisition of learned flavor aversions,
      and that hypotension may play a role in the elevated intake of saline by BDL
      rats.

PMID- 9523897
TI  - Comparative study of behavioral development between high and low shuttlebox
      avoidance rats.
AB  - Previously, we reported that high- and low-avoidance animals (HAA and LAA,
      respectively), selectively bred for different avoidance response rates in a
      shuttlebox avoidance test, showed additional behavioral differences in wheel cage
      activity and in water maze performance after weaning. In the present study,
      physical and behavioral development were examined in HAA and LAA during the
      preweaning period. As compared to HAA, LAA offspring showed lower body weight,
      delayed eye opening, poorer performance in pivoting and negative geotaxis, and
      increased open-field activity. A fostering study indicated that these differences
      observed in eye opening, pivoting, negative geotaxis, open-field activity,
      swimming speed, shuttlebox avoidance and wheel cage activity were independent of
      maternal care. Only the pup weight was strongly dependent on the maternal line.
      These results indicate that behavioral differences between HAA and LAA observed
      in the pre- and postweaning periods may be linked to the avoidance genotype, but
      the difference in pup weight may be caused by maternal care.

PMID- 9523898
TI  - Circadian control of insulin secretion is independent of the temporal
      distribution of feeding.
AB  - To investigate whether there is a circadian regulation of insulin secretion, rats
      were adapted to a feeding regimen of six meals equally distributed over 24 h.
      Under these conditions basal glucose and insulin levels increased during the
      light phase and decreased during the dark phase. Maximal blood glucose responses
      were fairly similar during the six different meals, but glucose increments were
      clearly delayed during the last two meals consumed during the light period.
      Insulin increments were highest during the dark phase and clearly diminished
      during the second half of the light phase. This situation was reversed when the
      scheduled meals were replaced by i.v. glucose infusions, i.e., no significant
      differences were detected between insulin responses, whereas glucose increments
      were reduced during the dark period. These results show that there is a circadian
      regulation of basal blood glucose and feeding-induced insulin responses, which is
      independent of the temporal distribution of feeding activity.

PMID- 9523899
TI  - Behavioral and endocrine change following chronic predatory stress.
AB  - Adult male rats showed very high levels of crouching when exposed to a cat, with
      suppression of the nondefensive behaviors (e.g., lying, locomotion, rearing) that
      were shown by toy cat-exposed controls. The crouching of cat-exposed rats
      declined slightly but reliably with increasing time within daily 60-min exposure
      sessions. However, the lack of a reliable cat-exposure x days interaction for
      crouching over the 20 days of testing indicated minimal habituation of the rats'
      defensive response to the cat over this exposure schedule, although rat and cat
      were separated by a wire mesh screen, precluding contact and pain. Following the
      20th day of exposure, cat-exposed rats showed reliably higher basal plasma
      corticosterone levels, suggesting a lack of habituation of this stress-linked
      response as well. Adrenal weights were also higher and thymus weights lower in
      these animals compared with controls, while spleen and testes weights and
      testosterone levels were not reliably different. Of the 13 cat-exposed subjects,
      6 (and a single control) failed to show a 10 microg/mL corticosterone (CORT)
      increase in response to an acute restraint stressor. In 3 of these 6 cat-exposed
      rats, the failure to meet this criterion was attributable to a low level of CORT
      following restraint, suggesting failure of the normal CORT surge to the acute
      restraint stressor. These findings of organ weight changes, enhanced basal CORT,
      and reduced CORT response to stress in a subgroup of animals are similar to many
      of the phenomena obtained with other intense, chronic stressors such as
      subordination, and suggest that repeated predator exposure produces a pattern of
      intense behavioral and endocrine response that is very slow to habituate. Because
      it is a natural stressor for both male and female subjects, and one for which
      pain and even handling of the subject is unnecessary, cat exposure may provide a
      particularly relevant and adaptable paradigm for research involving analysis of
      gender effects on the stress response.

PMID- 9523900
TI  - Exploratory and displacement behavior in transgenic mice expressing high levels
      of brain TNF-alpha.
AB  - Studies reported recently have shown that tumor necrosis factor-alpha (TNF-alpha)
      a cytokine released by macrophages and monocytes plays a key role in inflammatory
      processes and immune and neuro-endocrine regulation. TNF-alpha is also produced
      in the central nervous system (CNS). However, the role of this cytokine in the
      CNS is largely unknown, although evidence indicates that it is involved in
      various neurobehavioral manifestations. Using transgenic mice expressing high
      amounts of murine TNF-alpha transgene in the neurons of the CNS, we investigated
      the stereotyped, exploratory, and displacement activities in the hole-board and
      black/white box. Transgenic mice and their normal control littermates were
      hybrids of the CBA x C57BL/6 genetic backgrounds and were obtained by
      backcrossing the CBA x C57BL/6 founder female and her progeny with F1 hybrid
      mates. Transgenic mice did not show changes in the stereotyped behavior on the
      hole-board, but they displayed several alterations in the exploratory activities
      both in the hole-board and black/white box. Transgenic mice also exhibited an
      increase in grooming when exposed to a highly unfamiliar environmental stimuli in
      the black/white box. The study suggests that supranormal endogenous TNF-alpha in
      the brain affects the behavioral responses to stressful conditions.

PMID- 9523901
TI  - Effects of a daylight cycle reversal on locomotor activity in several inbred
      strains of mice.
AB  - There is some evidence of melatonin implication in the nycthemeral regulation of
      running activity rhythm in rodents. Because some inbred strains of mice such as
      C57BL/6 and BALB/c have been generally found to present no nocturnal melatonin
      peak, in contrast to others such as C3H/He and CBA mice, the aim of this study
      was to examine the adaptation of daily locomotor activity to a light/dark cycle
      phase shift in these four strains. An apparatus consisting of two boxes connected
      by a tunnel was used to record spontaneous locomotor activity, defined as the
      number of transitions between the two boxes. Locomotor activity was monitored
      continuously during 3 days before and 14 days after a 12-h phase delay of the
      light/dark cycle. Results essentially showed that the adaptation of the locomotor
      activity rhythm to the phase shift was faster in C57BL/6 and BALB/c mice than in
      C3H/He and CBA mice. This could be related, at least in part, to the differences
      in melatonin synthesis between the former strains and the latter ones. Although
      melatonin nocturnal peak is not necessary to a daylight regulation of circadian
      functions in rodents, it could be considered as an endocrine message that takes
      part in the anticipation of the following light/dark cycle.

PMID- 9523902
TI  - Interleukin-1-induced sickness behavior depends on behavioral lateralization in
      mice.
AB  - Inter-individual differences in brain-immune interactions have been demonstrated
      previously in mice using lateralization as a behavioral trait of population
      heterogeneity. Lipopolysaccharide (LPS), which is known to induce neurochemical,
      neuroendocrine, and immune responses depending on lateralization, is also able to
      induce sickness behavior, via the production of interleukin-1 (IL-1). The
      objective of this study was to determine whether lateralization can influence the
      behavioral response to LPS and to IL-1. To test this hypothesis, adult female C3H
      mice, previously selected for paw preference in a food reaching task, were
      injected intraperitoneally (i.p.) with 0.75 microg LPS or 0.75 microg recombinant
      IL-1beta. Sickness induced by these molecules was measured by depressed social
      behavior, increased immobility, loss of body weight, and reduced food intake
      during the 6 h following injection. LPS-induced sickness was similar in right-
      and left-pawed mice. In contrast, IL-1-induced sickness behavior was dependent on
      behavioral lateralization. IL-1-induced depression of social investigation was
      more pronounced in right-pawed mice than in left-pawed animals. Likewise, IL-1
      induced immobility was more important in right-pawed mice. There was a similar
      trend for food intake to be lower and loss of body weight to be higher in right
      pawed mice than in left-pawed animals. These results demonstrate that right-pawed
      mice are more sensitive to IL-1-induced sickness than left-pawed animals. They
      extend our previous data showing a greater susceptibility to stress of right
      pawed animals. The existence of inter-individual differences in the reactivity to
      stress or immune activation may be useful to study the mechanisms of the various
      strategies used by an individual in response to environmental aggressions.

PMID- 9523903
TI  - Concurrent monitoring of EEG and performance in the common marmoset: a
      methodological approach.
AB  - A model has been developed in a nonhuman primate, the common marmoset (Callithrix
      jacchus), which should enable the study of long term effects of compounds with
      potentially psychoactive properties. The technique facilitates concurrent
      monitoring of both behavioral and electrophysiological parameters while animals
      remain in their home cages. Subjects were trained to perform tests from a
      neuropsychological test battery (The Cambridge Neuropsychological Test Automated
      Battery, CANTAB) in which they learned to discriminate between pairs of stimuli
      presented on a touch sensitive computer screen. Single channel cortical
      electroencephalography (EEG) by radiotelemetry was simultaneously recorded while
      behavioral testing took place.

PMID- 9523904
TI  - Effects of a high NaCl diet on eating and drinking patterns in pygmy goats.
AB  - Eating and drinking patterns of eight pygmy goats were recorded under two diets
      with different NaCl content. A 3% NaCl diet in comparison to a 0.5% NaCl diet
      caused a long lasting depression of food intake, whereas water intake did not
      change. Therefore, the ratio between cumulative water and food intake increased
      significantly. Feeding the 3% NaCl diet mainly decreased food intake through a
      decrease in the size (31%) and frequency (16%) of meals which were not associated
      with drinking. Size and frequency of meals associated with drinking were not
      substantially affected by the 3% NaCl diet. Size and frequency of drafts were not
      altered. Size of meals associated with drinking was generally bigger than that of
      meals not associated with drinking. These findings can best be explained by
      control of feeding through osmolality of rumen fluid. Ruminal osmolality seems to
      be less important for control of drinking.

PMID- 9523906
TI  - The relationship between the putative optic pathway potential and the
      electroretinogram.
AB  - The putative optic pathway flash visual evoked potential (FVEP) and the
      electroretinogram (ERG) were recorded consecutively in the lightly anesthetised
      rat. The purpose was to test the hypothesis that the optic pathway FVEP is only
      an artifact created by distorted volume-conducted retinal activity. A comparison
      of the timing of the ERG with that of the optic pathway FVEP confirmed this
      suspicion. It is shown that there is a close temporal correspondence between
      individual subcomponents of the optic pathway potential and those of the ERG
      (i.e., the a-wave, b-wave, and the oscillatory potentials). In addition, it was
      found that when ERG currents are recorded far field from the vicinity of the
      optic nerve or tract, they acquire a triphasic positive-negative-positive
      waveform, thereby heightening the illusion that the optic pathway FVEP is a
      genuine compound action potential. It is concluded that experimental findings
      derived from the recording of the optic pathway FVEP must be treated with
      caution.

PMID- 9523905
TI  - Social stress in loser rats: opposite immunological effects in submissive and
      subdominant males.
AB  - The impact of chronic confrontation on behavior, body weight, and aspects of
      blood cellular immunity was investigated in 24 Long Evans intruder rats. At the
      beginning of a 1-week confrontation period, an adult male was introduced into a
      one male-one female resident group which resulted in fights for dominance.
      Although most intruders became losers in this situation, their specific behavior
      differed. Two groups of losers were defined: subdominant (N = 11) and submissive
      intruders (N = 9). In contrast to subdominant intruders, submissive males often
      displayed behaviors indicating social defeat. They were frequently involved in
      agonistic interactions and lost 7% of their initial body weight. Confrontation
      provoked marked changes in many measures of blood cellular immunity. Importantly,
      the immunological effects differed significantly in magnitude and direction
      depending on the individuals' behavior. Submissive males reacted with reduction
      in lymphocyte proliferation in response to ConA and shifts in lymphocyte subsets
      (decline in percentage of CD4 and CD8 T cells, increase of B cells), but with
      little change in lymphocyte numbers. In addition, a pronounced increase in
      granulocytes was evident. In contrast, in subdominant males lymphocyte, T cell,
      and B cell counts were lowered but no change in subset composition occurred. The
      effects on T and B cell composition were not fully reversible within 7 days after
      end of the confrontation period indicating long-term consequences for migration
      of lymphocyte subsets. These data show that a detailed behavioral analysis is
      required for a meaningful biological evaluation of social stress-induced immune
      changes in rats, because different coping strategies result in different
      immunological consequences.

PMID- 9523908
TI  - Effects of cocaine on adrenal sympathetic nerve discharge in anesthetized rats.
AB  - Cocaine increases the circulating levels of plasma catecholamines, presumably via
      the activation of the sympathoadrenal axis. However, a number of reports have
      shown that the predominant response to cocaine is a generalized decrease in
      sympathetic nerve activity. One possible explanation for the increase in plasma
      catecholamines may be that the adrenal sympathetic nerve is less sensitive to the
      sympathoinhibitory actions of cocaine than are other nerves. This study compared
      the effects of cocaine on adrenal and renal sympathetic nerve discharge (SND)
      recorded simultaneously in pentobarbital-anesthetized rats. Cocaine produced dose
      related decreases in both renal and adrenal SND; however, the decreases in
      adrenal SND were significantly smaller than in renal SND. Cocaine also elicited
      pressor responses in these rats. The decreases in adrenal SND were similar in
      baroreceptor intact and sinoaortically denervated rats, indicating that pressor
      mediated baroreceptor reflex activation was not responsible for the decrease in
      adrenal SND. In a separate group of rats, i.v. administration of desipramine
      decreased both adrenal and renal SND. As with cocaine, the decreases in adrenal
      SND after desipramine were smaller, suggesting that the differences in the neural
      responses did not reflect a differential local anesthetic effect of cocaine on
      the two nerves. In conclusion, these studies showed that cocaine decreases
      adrenal SND in pentobarbital-anesthetized rats. However, the adrenal sympathetic
      nerve is less sensitive than the renal nerve to the sympathoinhibitory actions of
      cocaine. Whether the adrenal SND remaining after cocaine contributes to the
      increase in plasma catecholamines produced by this drug remains to be determined.

PMID- 9523907
TI  - Effects of carbohydrate and lipid on resting energy expenditure, heart rate,
      sleepiness, and mood.
AB  - The effects of gastric infusions of fat and carbohydrate on physiological and
      psychological measures were compared using a within subject design in 9 healthy
      subjects (6 males). Each subject received isovolaemic rapid gastric infusions of
      sucrose solution (100% energy carbohydrate), lipid emulsion (100% energy fat, 20%
      Intralipid), and a non-nutrient control (0.9% saline) in a randomised order.
      Nutrient infusions were isoenergetic, containing one-third of an individual
      subject's estimated daily energy requirements (mean, 3227 kJ; range, 2479-3971
      kJ). Measures of heart rate (HR), energy expenditure (EE), mood, and sleepiness
      were collected before the infusions and every 0.5 h for 3.5 h. Mean postingestive
      HR, EE, and satiation were significantly greater after the nutrient infusions
      than after the control. Sucrose induced a rapid increase in HR and EE, whereas
      lipid had a lesser and more delayed effect. Thirty minutes after the gastric
      infusions, HR and EE were significantly higher after the sucrose than after the
      lipid and saline. Hedonic tone was greater and tension lower after the saline and
      sucrose infusions than after the lipid infusion. From 3 to 3.5 h after ingestion,
      subjects felt significantly more sleepy after the lipid infusion than they did at
      these times after the saline infusion, and significantly more dreamy after the
      lipid infusion than they did after the sucrose infusion. In conclusion, the
      presence of lipid and sucrose in the intestine induces significant and differing
      physiological and psychological effects, which are independent of cognitive and
      orosensory influences.

PMID- 9523909
TI  - A comparison of visual- and response-generated cues in a spatial DMTS task for
      rats.
AB  - In an attempt to clarify the nature of the memory cues used in a spatial, working
      memory task, rats were tested in a two-choice water maze. Each trial consisted of
      an information run, which forced the rat to the correct choice compartment, a
      retention period, and a test run. A response-associated cue condition, in which
      the relevant cue was the direction of the turn in the information run, was
      compared to a visual cue condition in which the animal had to remember whether
      the escape platform had been in the light or dark compartment. Of the subjects
      supplied with either visual or response-associated cues, the subjects allowed to
      employ response-associated cues did better, but the best performance occurred
      when both cues were available. When rats trained with both cues present were
      forced to choose between cues, they stopped using either and reverted to making a
      preferred right or left turn. The results support the idea that rats can form
      integrated, relational-cue memories which, in some circumstances, prove a
      hindrance to performance.

PMID- 9523910
TI  - Long- and short-term habituation of acoustic startle is not frequency specific in
      the rat.
AB  - Two experiments examined the frequency specificity of habituation of the acoustic
      startle response in the rat. Following the long-term habituation of startle to
      one of two pure tone stimuli in Experiment 1, animals were presented with the
      other stimulus. Startle response asymptotes were unaffected by this change in
      stimulus frequency. Short-term habituation of startle also was insensitive to
      stimulus frequency. In Experiment 2, pure tone stimuli were used to provoke both
      a startle response and the interruption of drinking. Long-term habituation of
      startle to either stimulus was unaffected by a change in frequency. Animals that
      received the two stimuli on alternating days showed as rapid a habituation as did
      the groups receiving only one stimulus frequency during acquisition. Conversely,
      the lick suppression measure was found to be frequency specific. Lick suppression
      durations rose to pre-habituation levels when the frequency of the stimulus was
      changed. Animals that received the two stimuli on alternating days showed
      retarded habituation compared to those groups presented with only one stimulus
      frequency during acquisition. Although long-term habituation of startle is not
      stimulus specific, it is mediated by central processes and thus remains a
      valuable model in the study of neurophysiological mechanisms of behavioral
      change.

PMID- 9523912
TI  - Pretest CS cueing facilitates the recovery of avoidance behavior following visual
      cortex lesions in the rat.
AB  - Rats were trained on a four-way shuttle box with a compound light-tone
      conditioned stimulus (CS) until they emitted 7 avoidance responses in 10 trials
      (7/10) prior to bilateral ablation of the visual cortex or sham surgery. On Day 5
      after surgery, rats were cued with either the compound light-tone CS, the light
      or tone portion of the CS only, or had no exposure to the CS. On Day 10 after
      surgery, all animals were tested for avoidance retention under the same
      conditions as preoperative training. The findings indicate that following a
      lesion, cueing with the light-tone compound CS facilitates performance as does
      light alone. Cueing to the tone alone has no effect. In sham animals, only cueing
      with the light-tone CS was effective in enhancing avoidance retention. Results
      are interpreted as early and modality-specific sensory cueing may facilitate the
      recovery process.

PMID- 9523911
TI  - Histology and enzymatic activity in the postnatal development of limb muscles in
      rodents.
AB  - The present work examines how increases in spontaneous motor capabilities during
      postnatal development are reflected in enzymatic activity and the histology of
      hindlimb muscles of the dormouse (Eliomys melanurus), the jird (Meriones
      tristrami), the vole (Microtus socialis), and the spiny mouse (Acomys cahirinus).
      The precocial neonate of the spiny mouse had the most advanced developmental
      state of young myofibers with striations as early as 1 week after delivery. At
      the same age, the altricial neonate vole had less developed muscles compared to
      the spiny mouse, but was more mature compared to other altricial species. The
      dormouse was the least developed, with numerous myoblasts and few myotubes at 1
      week after delivery. These differences in myogenic development were conspicuous
      throughout postnatal development. Similar differences between the species were
      also evident at the biochemical level, as measured in the kinetics of activity of
      the enzyme creatine-phosphokinase immediately after delivery. On postnatal day 7,
      the creatine-phosphokinase level in the spiny mouse was fourfold higher than in
      the dormouse or vole. The enzymatic activity of acid phosphatase decreased during
      the first week postdelivery in the spiny mouse while peaking in the first,
      second, and third week in the jird, vole, and dormouse, respectively. These
      results support the notion that precocial species undergo certain developmental
      stages in utero, whereas, the same stages commence in altricials only
      postnatally. For the tested altricial species, the results illustrate that limb
      muscles in the vole, which displays more basic gaits, mature before limb muscles
      of the jird and dormouse, which display more specialized gaits.

PMID- 9523913
TI  - Responses of slaughter pigs to transport and lairage sounds.
AB  - The behavioral and physiological responses of pigs to transport and subsequent
      exposure to slaughterhouse sounds were examined. Forty-one groups of four
      slaughter pigs were separately loaded onto a lorry and transported for 25 min.
      Another 43 groups were loaded onto the lorry which then remained stationary for
      25 min. Following unloading pigs were moved to a race with a length of 15 m and a
      width of 1.5 m. Either one of the following sounds was played at 85 dB(A) for 10
      min: Pigs in front of the restrainer, Machines in lairage, White Noise, or
      Control (no sound). Pigs exposed to the Machines and White Noise treatment spent
      significantly more time close to their group-mates compared with Control pigs,
      with pigs subjected to the Pig sound being intermediate. Transported pigs spent
      less time exploring the race and were less active than pigs from the stationary
      lorry. Heart rate was higher during transport than during the stationary period.
      In contrast, during unloading, the sound exposure period and the post-sound
      period, heart rate was lower in the transported groups. Heart rate did not
      significantly differ between sound treatments. Salivary cortisol concentrations
      were significantly higher after transport than after the stationary period and
      remained higher for transported pigs after the sound exposure period. Cortisol
      levels did not differ significantly between sound treatments. It is tentatively
      suggested that social support from conspecifics may protect pigs from potentially
      adverse effects of exposure to lairage sounds.

PMID- 9523914
TI  - Influence of male-related stimuli on female postejaculatory refractory period in
      rats.
AB  - Female rats "pace" their sexual contacts with the male when tested in situations
      where they can escape from the male during copulation. The type and quality of
      vaginocervical stimulation that the females receive during copulation influences
      their pacing behavior. This study investigated the effect of several male-related
      stimuli on the female's postejaculatory refractory period (PER). Females were
      tested in a two-compartment test chamber from which they could escape the male
      through one of four openings along the bottom of the barrier separating the two
      compartments. Experiment 1 examined the influence of the seminal plug, the penile
      cup, and prostate secretions on the female's PER. Results showed that neither the
      seminal plug, the penile cup, nor prostate secretions contributed to the female's
      PER. Experiment 2 investigated the relation of pre-ejaculatory intromission
      frequency, ejaculation duration, and the number of pelvic thrusts during
      ejaculation to the female's PER. Results indicated that pre-ejaculatory
      intromission frequency and ejaculation duration but not the number of pelvic
      thrusts during ejaculation were significantly correlated with the female's PER.
      In addition, pre-ejaculatory intromission frequency was significantly correlated
      with ejaculation duration. Partial correlation analysis suggested that pre
      ejaculatory intromission frequency affected ejaculation duration which, in turn,
      influenced the female's PER. This finding was further supported by the evidence
      that ejaculation duration and the female's PER were significantly shorter in
      tests in which the male ejaculated on the first or second intromission.

PMID- 9523915
TI  - Magnetic field conditioned taste aversion in rats.
AB  - Conditioned taste aversion is a common classic conditioning procedure used to
      identify noxious stimuli. When a rat is given a taste solution, the conditioned
      stimulus (CS), followed by an unpleasant experience, the unconditioned stimulus
      (US), the rat will avoid consumption of the CS in future presentations. These
      experiments use the taste aversion procedure to examine the effect of exposure to
      a high magnetic field. A solution consisting of 3.0 g glucose and 1.25 g
      saccharin per 1 L of solution (G+S) was used as the CS and a 9.4-T magnet served
      as the US. In Experiment 1, all rats received a 10 min presentation of the G+S
      solution followed by either a 30 min exposure to the magnetic field (Magnet, n =
      8), a 30-min exposure in a container with similar conditions but lacking the
      magnetic field (Sham, n = 8), or no exposure (Control, n = 8). The Magnet Group
      showed a taste aversion on the first day of preference testing (p < 0.05).
      Experiment 2 employed the same US-CS protocol for 3 consecutive days of
      conditioning. The Magnet Group demonstrated a taste aversion for the postexposure
      Days 1-8 (p < 0.01). There was no difference between the Sham and Control Groups
      in either experiment. The results of this study clearly demonstrate that the rats
      associated the G+S solution with the experience of being exposed to the high
      magnetic field and avoided the solution in subsequent presentations.

PMID- 9523916
TI  - Endotoxin tolerance does not alter open field-induced fever in rats.
AB  - Exposure to an open field has been shown to cause a rise in the body temperature
      of rats. In many respects, this rise in body temperature is similar to fevers
      caused by endotoxin and other inflammatory stimuli. Rats repeatedly injected with
      endotoxin develop tolerance to the fever-inducing action of endotoxin. We
      hypothesized that repeated pretreatment with endotoxin would modify the fever
      caused by exposure to psychological stress. To test this hypothesis, we compared
      open field-induced fevers in rats made endotoxin tolerant to those rats not
      endotoxin tolerant. We found that endotoxin tolerance had no effect on open field
      fevers.

PMID- 9523917
TI  - The effects of acute and repeated restraint stress on the nociceptive response in
      rats.
AB  - The effects of acute and repeated restraint stress on nociception, as measured by
      the tail-flick latency, were studied in adult male and female rats. After the
      exposure to a single restraint session, both male and female rats presented an
      increased latency in the tail-flick test. On the other hand, chronically stressed
      females presented a performance similar to the control group, whereas chronically
      stressed male rats responded to restraint with a decrease in the tail-flick
      latency. This response could be determined by the chronic treatment itself or by
      the restraint done just before the measurement. Thus, the effect of chronic
      stress upon basal tail-flick latency was evaluated. In male rats, this latency
      was significantly decreased in the stressed animals compared with the control
      group. In female rats, no difference between those groups was observed.
      Therefore, the results suggest that: (a) acute restraint stress induces an
      analgesic response in both male and female rats, and (b) there is a gender
      specific nociceptive response induced by repeated restraint stress with a
      hyperalgesic effect in response to stress only in males.

PMID- 9523918
TI  - Salt preference in adolescence is predicted by common prenatal and infantile
      mineralofluid loss.
AB  - We investigated early determinants of salt preference in humans. In animals,
      physiological events, among them perinatal mineralofluid loss, contribute to long
      term salt intake. Recent findings suggest that in humans prenatal mineralofluid
      loss (high levels of maternal vomiting) may increase the lifelong avidity for
      salt in offspring. Here we report that commonly occurring events that cause mild
      fluid loss and electrolyte imbalance in infancy, as well as prenatally, predict
      the avidity for salt in adolescents. Using questionnaires, 50 mothers recalled
      incidence and severity of infantile diarrhea and vomiting in their adolescent
      offspring. The adolescents' avidity for salt was determined by testing the
      preferred concentration of salt in soup, voluntary consumption of salty snack
      items, and by self report of salt use habits, and a dietary questionnaire. A
      reported history of mineralofluid loss including maternal vomiting and infantile
      vomiting and diarrhea increases the avidity for salt but not for sweet. Thus,
      commonly occurring early mineralofluid loss may contribute to lifelong salt
      intake. The findings raise the possibility that other causes of mineralofluid
      loss such as hemorrhage, exercise-induced dehydration, or neonatal diuretic
      therapy may also increase the avidity for salt, and its attendant health risks.

PMID- 9523919
TI  - Visual discrimination in pigeons impaired by glutamatergic blockade of nucleus
      accumbens.
AB  - The nucleus accumbens septi (Acc) is thought to be involved in the control of
      cognitive processes and to be implicated in the pathophysiology of schizophrenia.
      Because perceptual-cognitive distortions are a core symptom in schizophrenia, any
      evidence that the Acc intervenes in a sensory recognition task in an animal
      species would be of interest. Pigeons were instrumentally trained to discriminate
      visual shapes. The acute effects of drug microinjections into the Acc on the
      discrimination of the training shapes, on the correction responding after errors,
      and on the generalisation to different shapes were examined. The effects of
      conduction blockade with lidocaine, glutamatergic blockade with 7
      aminophosphonoheptanoic acid, and dopaminergic stimulation with apomorphine on
      behavioural performance were tested. No effects were observed with lidocaine and
      apomorphine. A significant and reversible performance disruption to near chance
      levels was obtained after aminophosphonoheptanoic acid injections into the Acc.
      It appears that a glutamatergic blockade of the Acc interferes with the visual
      discrimination processes of pigeons.

PMID- 9523920
TI  - Intracerebroventricular cholecystokinin A-receptor antagonist does not reduce
      satiation by endogenous CCK.
AB  - Suppression of sham feeding by exogenous CCK-8 or intraintestinal oleate infusion
      is attenuated by peripheral administration of the CCK-A receptor antagonist,
      devazepide, but not by the CCK-B antagonist, L365260. Likewise, systemically
      administered devazepide increases food intake by real feeding rats. These results
      suggest that endogenous CCK participates in the reduction of food intake by
      intestinal oleate and ingested food. Although originally categorized as a
      "peripheral" receptor subtype, the CCK-A receptor is also present in the brain.
      In an effort to examine whether devazepide acts in the brain or in the periphery
      to attenuate suppression of food intake by intraintestinal oleate, we injected
      devazepide into the lateral or fourth cerebral ventricles of intraintestinally
      infused, sham-fed rats. We also compared the ability of intracerebroventricular
      (i.c.v.) and intraperitoneal (i.p.) devazepide to elicit increased food intake in
      real feeding rats. Doses of devazepide that were sufficient to attenuate or
      abolish oleate-induced suppression of sham feeding, when administered i.p.,
      failed to attenuate suppression of intake when administered i.c.v., i.p.
      devazepide also was more effective than i.c.v. devazepide for attenuation of the
      suppression of sham feeding by i.p. injection of exogenous CCK-8. Finally, i.c.v.
      devazepide was ineffective for increasing real food intake, whereas the same dose
      administered i.p. significantly increased food intake. Our results do not support
      participation of brain CCK-A receptors in the suppression of food intake by
      exogenous CCK, or by endogenous CCK released after intraintestinal oleate
      infusion, or food intake.

PMID- 9523921
TI  - An improved method for precise control of light exposure at a known circadian
      time during an animal's subjective night.
AB  - The paper describes an electronic device that improves the feedback lighting
      (LDFB) developed previously. LDFB links environmental lighting conditions to
      locomotor or other monitored behavior. Subjective Night Light (SNL) has the
      following advantages over LDFB: it eliminates the multiple transitions between
      light and dark; it allows for precise control over lighting so that a light
      signal of variable duration can be phase locked to any phase of the subjective
      night; it dissociates to a much greater extent any potential cognitive perception
      of the link between locomotor activity and lighting; and it can be programmed
      easily. Finally, SNL retains the significant advantage of LDFB in its ability to
      maintain phase relationship with the endogenous biologic rhythms even in
      circumstances of phase-shifting or free-running conditions. The SNL system is
      made from components that can be purchased at most electronics outlets for less
      than US$100.

PMID- 9523923
TI  - Effects of L-arginine on angiotensin II-related water and salt intakes.
AB  - Nitric oxide (NO) has been implicated centrally as an inhibitory neuromodulator,
      acting in short feedback loops. Neurons capable of NO synthesis have been
      localized in various thirst-related hypothalamic nuclei. Intracerebroventricular
      (icv) injection of L-arginine (L-arg), the precursor for NO, has previously been
      shown to attenuate both dehydration- and angiotensin II (Ang II)-induced drinking
      behavior. The present study further examines the effects of L-arg on drinking. We
      confirmed that icv administration of L-arg (50 microg) reduced water intakes
      induced by both 24 h water deprivation and icv Ang II (250 ng). We additionally
      showed that L-arg inhibited the water intake induced by peripheral injection of
      Ang II and the intake of 0.3 M NaCl following 24 h sodium depletion. We
      demonstrated the behavioral specificity of L-arg treatment by showing that it did
      not inhibit the intake of sucrose in food deprived rats and did not act as an
      unconditional stimulus for the formation of a conditioned taste aversion. These
      results lend further support to the idea that NO plays a role in modulating fluid
      balance and drinking behavior.

PMID- 9523922
TI  - A beta-3 adrenergic agonist (BRL-37,344) decreases food intake.
AB  - This study evaluated the effect of peripheral injections of a beta3 adrenergic
      agonist, BRL-37,344 on food intake and whether this inhibition could be blocked
      by a nonspecific beta-adrenergic antagonist, propranolol, given peripherally or
      into the central nervous system. When BRL-37,344 was injected intraperitoneally
      (i.p.) into lean and obese Zucker rats, food intake was decreased. The reduction
      of food intake by BRL-37,344 was attenuated when propranolol was administered
      i.p. prior to giving the beta adrenergic agonist. When propranolol was
      administered into the third cerebral ventricle, it increased food intake in lean
      rats, but not the fatty rats. Propranolol administered into the third cerebral
      ventricle attenuated the effect on food intake of i.p. injection of BRL-37,344.
      These studies support the hypothesis that there are peripheral beta-3 adrenergic
      receptors that can reduce food intake and that there are central beta2 or beta3
      adrenergic receptors that mediate the peripheral effect of the beta3 agonist.

PMID- 9523925
TI  - Out-of-hospital spinal immobilization: is it really necessary?

PMID- 9523924
TI  - An inexpensive new device to provide random rewards for behavioral studies.
AB  - Behavior modification in rats often involves controlling the frequency of
      providing food rewards. This is accomplished with computer-controlled devices or
      equipment purchased specifically for this purpose. Investigators currently choose
      from a few commercially available models, but each has its disadvantages or
      limitations, including a high cost (about US$1000). Computer-controlled devices
      can also be expensive and need a dedicated machine and software packages to
      perform the tasks. We designed a custom-built device to reward an action randomly
      from 1 out of 10 times to 10 out of 10 times. The device can be manufactured
      easily and inexpensively (about US$150). It has been in use for several months in
      our laboratories with no malfunctions.

PMID- 9523926
TI  - Antipersonnel land mines: why they should be banned.

PMID- 9523927
TI  - Randomized, controlled trial of inhaled budesonide as an adjunct to oral
      prednisone in acute asthma.
AB  - OBJECTIVE: To compare the clinical effect of nebulized budesonide with placebo in
      acute pediatric asthma. METHODS: A randomized, controlled, double-blind trial
      with parallel design was used in the ED of a tertiary care children's hospital.
      Children aged 6 months to 18 years with a moderate to severe exacerbation of
      asthma [Pulmonary Index Score (PIS) > or = 5 or < or = 11 after a salbutamol
      nebulization of 0.15 mg/kg] were eligible. All patients received prednisone 1
      mg/kg orally and nebulized salbutamol (0.15 mg/kg) every 30 minutes for 3 doses
      and then every hour for 4 hours. The intervention was 2 mg (4 mL) of nebulized
      budesonide or 4 mL of nebulized normal saline. RESULTS: Baseline characteristics
      were comparable in the budesonide group (n = 24) and in the placebo group (n =
      20). There were no significant differences in the primary outcome measure (PIS)
      between the 2 groups. However, the PIS at 1 hour had a tendency to be lower in
      the budesonide group (median = 5) as compared with the placebo group (median = 6;
      p = 0.07). Survival analysis of release/discharge from the ED/hospital showed a
      more rapid rate in the budesonide group as compared with the placebo group (p =
      0.02). No adverse effects were seen. CONCLUSION: Although these preliminary
      results suggest that nebulized budesonide may be an effective adjunct to oral
      prednisone in the management of moderate to severe asthma exacerbations, a larger
      trial will be required before the widespread use of inhaled budesonide in acute
      asthma can be advocated.

PMID- 9523928
TI  - Out-of-hospital spinal immobilization: its effect on neurologic injury.
AB  - OBJECTIVE: To examine the effect of emergency immobilization on neurologic
      outcome of patients who have blunt traumatic spinal injuries. METHODS: A 5-year
      retrospective chart review was carried out at 2 university hospitals. All
      patients with acute blunt traumatic spinal or spinal cord injuries transported
      directly from the injury site to the hospital were entered. None of the 120
      patients seen at the University of Malaya had spinal immobilization during
      transport, whereas all 334 patients seen at the University of New Mexico did. The
      2 hospitals were comparable in physician training and clinical resources.
      Neurologic injuries were assigned to 2 categories, disabling or not disabling, by
      2 physicians acting independently and blinded to the hospital of origin. Data
      were analyzed using multivariate logistic regression, with hospital location,
      patient age, gender, anatomic level of injury, and injury mechanism serving as
      explanatory variables. RESULTS: There was less neurologic disability in the
      unimmobilized Malaysian patients (OR 2.03; 95% CI 1.03-3.99; p = 0.04). This
      corresponds to a <2% chance that immobilization has any beneficial effect.
      Results were similar when the analysis was limited to patients with cervical
      injuries (OR 1.52; 95% CI 0.64-3.62; p = 0.34). CONCLUSION: Out-of-hospital
      immobilization has little or no effect on neurologic outcome in patients with
      blunt spinal injuries.

PMID- 9523929
TI  - The potential benefit of a home fire safety intervention during emergency medical
      services calls.
AB  - OBJECTIVE: To determine how often house fires occur at 1- and 2-family dwellings
      visited previously by emergency medical services (EMS) personnel and whether
      these visits were missed opportunities for a point-of-contact home fire safety
      intervention. METHODS: A retrospective, consecutive, case series analysis of all
      Milwaukee Fire Department alarm responses during 1994 was performed. Measurements
      included date of service, type of response, property type, dollar loss estimate,
      number of injuries and fatalities, cause of alarm, and presence of an operational
      smoke detector. Descriptive, chi2, and relative risk statistics were used to
      describe the relationship between EMS responses and fire responses at 1- and 2
      family dwellings. RESULTS: The Milwaukee Fire Department dispatched 94,378
      requests for service to 43,556 addresses. 16,150 addresses generated multiple
      requests; 7.2% (1,162/16,150) were for an "alarm of fire" response [relative risk
      1.83 (95% CI: 1.69-1.99) for addresses with multiple requests vs those with a
      single request for service]. Most [62% (721/1,162)] of the addresses were visited
      by EMS personnel prior to the alarm; 28% (205/721) were 1- and 2-family
      dwellings. A mean of 1.8 (376/205) EMS responses occurred prior to the "alarm of
      fire" response; 121 addresses received 1 response, 46 received 2, 18 received 3,
      and 20 received > or = 4 responses. Of 169 addresses with complete data, there
      was a total fire dollar loss of $1,963,020 (1994) along with 32 injuries and 0
      fatalities. While 47% (80/169) of the 1- and 2-family dwellings had a smoke
      detector present, only 17% (29/169) of the dwellings had an operational smoke
      detector. CONCLUSIONS: A point-of-contact home fire safety intervention appears
      of potential benefit for frequent users of EMS care. Determination of the
      presence of an operational smoke detector in 1- and 2-family dwellings may be a
      useful injury prevention act during such EMS calls.

PMID- 9523930
TI  - N-acetylcysteine reduces methemoglobin in an in-vitro model of glucose-6
      phosphate dehydrogenase deficiency.
AB  - OBJECTIVE: To determine whether N-acetylcysteine (NAC) reduces methemoglobin
      (MHB) in an in-vitro model of glucose-6-phosphate dehydrogenase (G6PD)
      deficiency, given that methylene blue is an ineffective MHB antidote in G6PD
      deficiency. METHODS: Five volunteers donated blood, which was divided equally
      into 2 test tubes, centrifuged, and washed with Tris-Mopps buffer (pH 7.4, 15
      mmol/L glucose). Both tubes were incubated with epiandrosterone (EA) (400
      micromol), a specific inhibitor of G6PD. After 75 microL of 0.18 mol
      hydroxylamine (HA) was added to induce MHB formation, 150 microL of NAC (20
      mg/mL) was added to tube 1 and 150 microL of phosphate-buffered saline (PBS) was
      added to tube 2 as a volume control. Serial MHB levels are reported as a
      percentage of total hemoglobin (Hb). G6PD activity was measured at baseline, 15
      minutes after EA, and at 5 hours. RESULTS: Mean G6PD activity at baseline was
      9.2+/-2.9 U/g Hb (normal >4.6 U/g Hb); 15 minutes after EA was 3.0+/-1.0 U/g Hb;
      and at experiment's end was 2.3+/-0.7 U/g Hb. The mean (+/-SD) areas under the
      concentration-time curves (AUCs) of NAC-EA-HA and PBS-EA-HA samples were compared
      using an unpaired t-test and were significantly different: PBS-EA-HA, 20,400+/
      1,100 % min, vs NAC-EA-HA, 10,400+/-1,000 % min, respectively (p < 0.05).
      CONCLUSION: In this in-vitro model of G6PD deficiency, NAC efficiently reduced
      MHB.

PMID- 9523931
TI  - Autonomic regulation of gastric ulcerogenesis after cervical cord transection in
      the rat.
AB  - OBJECTIVE: To examine the role of anticholinergic and sympathomimetic drugs in
      preventing gastric ulcerogenesis after cervical cord transection (CCT) in the
      rat. METHODS: A randomized, prospective, interventional trial was performed
      comparing pirenzepine (muscarinic type I receptor antagonist) and ephedrine
      (nonspecific sympathomimetic) in the prevention of gastric ulcerogenesis after
      CCT in the rat. After isoflurane-induced general anesthesia, group 1 (n = 12)
      received sham CCT with no pretreatment, group 2 received CCT with no
      pretreatment, group 3 received CCT with pirenzepine pretreatment (0.01/mg/kg IP),
      and group 4 received CCT with ephedrine pretreatment (3 mg/kg IP). Six hours
      after intervention, all the rats were euthanized with isoflurane, stomachs were
      dissected, and a gastric ulcer index was determined. RESULTS: The mean (+/- SD)
      ulcer index was 0.08 +/- 0.1 for group 1, 2.33 +/- 0.5 for group 2 (p = 0.01),
      0.41 +/- 0.7 for group 3 (p = 0.037 compared with group 2), and 0.75 +/- 0.7 for
      group 4 (p = 0.0005 compared with group 2). Groups 3 and 4 were not significantly
      different from each other (p = 0.30). CONCLUSIONS: Gastric ulcerogenesis after
      CCT in the rat is decreased by anticholinergic and sympathomimetic drug
      pretreatment.

PMID- 9523932
TI  - Predictive validity of the emergency physician and global job satisfaction
      instruments.
AB  - OBJECTIVE: To evaluate the predictive validity of the Emergency Physician Job
      Satisfaction (EPJS) and Global Job Satisfaction (GJS) instruments. METHODS:
      Prospective mail survey of 223 Canadian emergency physicians (EPs) using a 42
      item questionnaire, including 14 items evaluating their reasons for leaving
      emergency medicine (EM). Original (1990) EPJS and GJS scores were analyzed using
      1-way ANOVA and Scheffe's test comparing the physicians who left EM with those
      still in their original jobs, and those who had left their original jobs but who
      stayed in EM. Mean scores on the 14 "reason for leaving" items were compared with
      scores from an earlier sample of U.S. physicians using a t-test for independent
      means. Criteria for statistical significance were set at alpha = 0.05 for all
      analyses. RESULTS: The response rate for the primary study questions was 99.1%.
      Of the respondents, 29.4% had left their original jobs, and 10.4% had left EM
      altogether. The GJS scores for the physicians who left EM were significantly
      different from those for the physicians who stayed (p = 0.004). The EPJS scores
      for the physicians who left EM were not significantly different from those for
      the physicians who stayed (p = 0.56). There was no significant difference in
      scores between the Canadian and U.S. physicians' reasons for leaving EM (all p
      values > 0.05). Shiftwork scored the highest as a reason to leave EM.
      CONCLUSIONS: A low GJS score is associated with physicians' leaving EM, but not
      with changing jobs. The EPJS instrument was not associated with either outcome.
      Canadian and U.S. EPs place similar levels of importance on potential reasons for
      leaving EM.

PMID- 9523933
TI  - Incorporation of a "Coping with the Death of a Child" module into the pediatric
      advanced life support (PALS) curriculum.
AB  - OBJECTIVE: To develop an educational module for health professionals (HPs)
      addressing the clinical reality of death as an outcome of pediatric resuscitation
      efforts. Module goals were to: 1) reduce HPs' discomfort with situations
      involving patient death and survivor grief, 2) assist HPs coping with their own
      emotions surrounding a patient death, and 3) provide specific strategies useful
      in clinical management. The module was designed to be presented as part of the
      American Heart Association (AHA) and the American Academy of Pediatrics (AAP)
      Pediatric Advanced Life Support (PALS) provider course. METHODS: A
      multidisciplinary team created a module addressing both survivors' and HPs' needs
      regarding a PALS course "Coping with the Death of a Child" module. The module was
      presented to 964 PALS course participants. Content was revised after analysis of
      survey data collected from these participants. RESULTS: The revised module was
      presented to 601 PALS course participants; evaluations were obtained from 590
      participants. On a 4-point Likert scale, ratings were: 79% "excellent," 18%
      "good," 2% "fair," and <1% "poor." CONCLUSION: The PALS course offers an
      opportunity to target HPs likely to encounter pediatric deaths for special
      education. While this is a challenging and potentially controversial topic to
      present to a diverse audience, incorporation of a "Coping with the Death of a
      Child" module into the PALS provider curriculum appears to be both feasible and
      useful.

PMID- 9523934
TI  - Declining rate of cricothyrotomy in trauma patients with an emergency medicine
      residency: implications for skills training.
AB  - OBJECTIVE: To report the change in cricothyrotomy rate with emergency medicine
      (EM) residency development and to address the implications for training in this
      skill. METHODS: A retrospective chart review was used to determine the
      cricothyrotomy rate at a 1,000-bed urban Level-1 trauma center with EM, surgery,
      and anesthesiology residencies. All adult trauma patient visits to the ED between
      July 1, 1985, and June 30, 1995, were reviewed. The cricothyrotomy rate was
      defined as the total number of cricothyrotomies per trauma admissions during a
      study phase. RESULTS: The study period was divided into 3 phases. Phase 1
      (academic years 1985-1989): prior to the inception of the EM residency; phase 2
      (academic years 1990-1992): initiation and establishment of the residency; and
      phase 3 (academic years 1993-1994): full implementation of the EM residency. The
      cricothyrotoiny rate during phase 1 was 1.8% (95% CI: 1.6 to 2.0), vs 1.1% (95%
      CI: 0.0 to 2.8) and 0.2% (95% CI: 0.0 to 0.2) during phases 2 and 3,
      respectively. CONCLUSIONS: The cricothyrotomy rate decreased with the full
      implementation of the EM residency. Whether this trend was an effect of the
      presence of an EM faculty and residency training program, a parallel approach to
      airway management nationwide, or another unidentified factor will require further
      investigation. Nonetheless, given the increasing rarity of this procedure, it is
      likely that many EM, surgical, and anesthesiology residents will not acquire
      clinical experience with this technique during training.

PMID- 9523935
TI  - Program for reducing pedestrian-motor vehicle crashes.
AB  - Injury prevention has been identified as a component of emergency medicine.
      However, involvement of emergency physicians in injury prevention has been
      hindered by clinical responsibilities, lack of financial support, and limited
      expertise in skills necessary for effective injury prevention programs. This
      article describes the development and content of a statewide pedestrian safety
      plan prepared by the Department of Emergency Medicine at the University of New
      Mexico. The plan included a written document, community input through focus
      groups, and a public information campaign. The written document included a
      synthesis of published literature, state-specific data, information on community
      interventions, and recommendations for state agencies and other groups interested
      in reducing pedestrian injuries. This project can be modeled at other academic
      EDs with an interest in injury prevention and pedestrian safety.

PMID- 9523936
TI  - Statistical methodology: IV. Analysis of variance, analysis of covariance, and
      multivariate analysis of variance.
AB  - Medical research frequently involves the statistical comparison of >2 groups,
      often using data obtained through the application of complex experimental
      designs. Fortunately, inferential statistical methodologies exist to address
      these situations. Analysis of variance (ANOVA) in its many forms is used to
      simultaneously test the equality of all groups in a study. One-way (with 1
      independent variable), 2-way (with 2 independent variables), and repeated
      measures (patients serve as their own controls) ANOVAs are forms of this
      technique. Each form has been developed to analyze data from a specific
      experimental design. Analysis of covariance (ANCOVA) allows the researcher to
      control for confounding variables that may influence the response of the
      dependent variable. Finally, multivariate analysis of variance (MANOVA) evaluates
      the simultaneous responses of multiple dependent variables to > or = 1
      independent variable. Whereas ANOVA is the correct alternative to statistically
      inappropriate multiple t-tests, MANOVA is the correct alternative to
      statistically inappropriate multiple univariate ANOVA calculations. Use of each
      of these statistical methods requires an appropriate experimental design and data
      meeting a number of assumptions. When used properly, each of these methods
      provides a powerful statistical analysis technique.

PMID- 9523938
TI  - Collaboration in emergency medicine research.

PMID- 9523939
TI  - Toward assessing outcomes of emergency care.

PMID- 9523940
TI  - More on assessing outcomes of emergency care.

PMID- 9523941
TI  - Information systems support for emergency medicine.

PMID- 9523942
TI  - Further thoughts on research funding.

PMID- 9523943
TI  - Unnecessary out-of-hospital use of full spinal immobilization.

PMID- 9523944
TI  - Substance abuse and emergency medicine: not so benign neglect.

PMID- 9523945
TI  - Survival needs of academic departments in county hospitals.

PMID- 9523946
TI  - Out on a limb.

PMID- 9523947
TI  - A comprehensive approach to surgical management of the type IIIA hypoplastic
      thumb.
AB  - In order to adequately identify pathologic anatomy and effectively reconstruct 14
      type IIIA hypoplastic thumbs, a comprehensive clinical evaluation and surgical
      approach was employed. Eleven patients had congenital differences in the forearm,
      while all patients had anomalies in the wrist, hand, and digits. In addition to
      well-described interconnections between the flexor pollicis longus and the
      extensor pollicis longus, and thenar muscle hypoplasia, the authors observed
      duplication of musculotendinous units, anomalous muscles between the thumb and
      index rays, and abnormal insertions or dense adhesions along tendons as proximal
      as the forearm level. Successful reconstruction required an extended approach
      from the digit to the forearm, through which division of abnormal connections,
      reorientation of tendons, and lysis of adhesions was performed. Opposition
      transfer was needed in only 8 of the patients after the other pathologies were
      treated. Web-space deepening and ulnar collateral ligament reconstruction was
      performed when indicated. Improvement in function and appearance was achieved.

PMID- 9523948
TI  - Camptodactyly: a unifying theory and approach to surgical treatment.
AB  - Camptodactyly is an isolated congenital flexion deformity of the proximal
      interphalangeal (PIP) joint. Surgical experience with 16 patients (18 fingers)
      between June 1983 and December 1994 is reported. Skin, fascia (retinaculum
      cutis), tendon sheaths, flexor digitorum superficialis tendon, lumbricals and
      interossei (particularly the lateral bands), joint surfaces, neck of the proximal
      phalanx, and central slip insertion were involved in all cases, although the
      degree of involvement can vary. Surgery must address all of these structures.
      Postoperative splinting is important. Fifteen patients had good or excellent
      results after surgery, with a mean gain in motion of 57 degrees (range, 0 degrees
      90 degrees). Surgery should be aimed at prevention of progressive deterioration
      and is probably not indicated in minor degrees of the deformity. Surgery should
      be reserved for patients with a preoperative PIP joint contracture of more than
      60 degrees.

PMID- 9523949
TI  - Type II (beta) errors in the hand literature: the importance of power.
AB  - When a study concludes that there is no difference between 2 treatments
      ("negative studies"), it is essential to determine whether the study has
      sufficient power to find a clinically significant difference. Insufficient power
      precludes an adequate assessment of therapeutic efficacy and may result in a type
      II error, an erroneous conclusion that the null hypothesis is correct. In
      evaluating 39 studies that highlighted negative findings in The Journal of Hand
      Surgery, we found that 32 (82%) papers had a power of less than .80 to detect a
      25% treatment effect and, when the treatment effect was increased to 50%, more
      than one half of the studies still had a power of 0.80. These "negative studies"
      frequently have inadequate statistical power to support their conclusions. These
      findings have important implications for researchers, editors, and readers.

PMID- 9523950
TI  - Expanded profile of the SHAFT syndrome.
AB  - The SHAFT syndrome is a factitious disorder in which a patient manipulates the
      surgeon to perform operations to fulfill his or her psychological needs. The
      acronym describes patients who are sad, hostile, anxious, frustrating, and
      tenacious. A chart review from January 1990 to June 1996 was undertaken to
      provide a profile to aid in the recognition and diagnosis of the SHAFT syndrome.
      An analysis of 28 patients revealed characteristics supporting a definitive SHAFT
      profile. Patients with SHAFT syndrome seek physicians to perform invasive
      procedures. Their typical complaint is pain, usually without objective physical
      findings that would support a more definitive diagnosis. Such patients tend to be
      women, cry with pain, describe symptoms out of proportion to objective findings,
      and have a history of psychiatric care.

PMID- 9523951
TI  - The prevalence of flexor digitorum superficialis and profundus muscle bellies
      beyond the proximal limit of the carpal tunnel: a cadaveric study.
AB  - A descriptive study was performed on 28 female (mean donor age, 64+/-21 years)
      and 26 male cadavers (mean donor age, 68+/-21 years) of mixed racial origin
      randomly sampled from 2 departments of anatomy. The objectives of the study were
      to determine the prevalence among the study population of the presence of flexor
      digitorum profundus and flexor digitorum superficialis muscle bellies within the
      proximal limit of the carpal tunnel and to investigate whether there were any
      sex, age, or stature differences in the study group. The female sample showed a
      46% prevalence of muscle bellies in the tunnel versus only 7.8% for the male
      sample. The mean muscle belly distance from the proximal limit of the carpal
      tunnel in female cadavers was significantly smaller (p < .02) than in the male
      cadavers. The distribution of muscle belly distance from the tunnel, however, was
      found to be the same in both the male and female cadavers. In female cadavers,
      the majority of the mean muscle belly distances were significantly correlated
      with forearm length, while in the male cadavers, this was the exception rather
      than the rule.

PMID- 9523952
TI  - Effects of forearm pronation/supination on carpal tunnel pressure.
AB  - The effects of forearm rotation and metacarpophalangeal (MP) flexion on carpal
      tunnel pressure were investigated in 17 healthy adults who had no evidence of
      carpal tunnel syndrome (CTS). Pressure was continuously recorded with a saline
      filled catheter inserted into the carpal tunnel and connected to a pressure
      transducer while test subjects slowly rotated the forearm from full pronation to
      full supination. Forearm rotation was repeated with MP flexion of 0 degrees, 45
      degrees, and 90 degrees. Both forearm rotation and MP flexion, and their
      interaction term, significantly affected carpal tunnel pressure and accounted for
      most of the variability in the data. Highest mean pressures (55 mmHg) were
      recorded in full supination and 90 degrees MP flexion and lowest pressures (12
      mmHg) were recorded at 45 degrees pronation and 45 degrees MP flexion. These data
      may be useful in the design of tasks and hand tools in the management and
      prevention of CTS.

PMID- 9523953
TI  - Changes in carpal tunnel pressures following endoscopic carpal tunnel release: a
      cadaveric study.
AB  - The purpose of this experiment was to determine the amount of tissue that must be
      sectioned to adequately decompress the median nerve during an endoscopic carpal
      tunnel release procedure. In 6 fresh cadaver forearms, 2 balloons were inserted
      into the carpal tunnel. The first balloon was filled with saline solution to
      cause an initial carpal intracanal pressure of 50 mmHg. Pressure measurements
      were recorded, using the second balloon, at various increments of the flexor
      retinaculum division at 3 wrist positions (neutral, 35 degrees ; flexion, 35
      degrees extension). At all increments of sectioning, carpal tunnel pressures in
      the neutral wrist position were consistently lowest and the values in 35 degrees
      extension were greatest. At each wrist flexion/extension angle, the pressure
      statistically decreased during incremental division of the flexor retinaculum.
      Incomplete release of the transverse carpal ligament resulted in incomplete
      decompression in the canal. Sectioning the overlying aponeurosis caused a further
      significant decrease in intracanal pressure.

PMID- 9523954
TI  - Temporal changes in grip and pinch strength after open carpal tunnel release and
      the effect of ligament reconstruction.
AB  - Symptoms of pain and weakness are nearly ubiquitous after carpal tunnel release.
      This study investigates the length of time before restoration of grip and pinch
      strength after open carpal tunnel release, in a population of patients without
      workers' compensation-related injuries. Two different forms of carpal ligament
      reconstruction were carried out in 2 groups of patients, and a third group
      underwent no ligament reconstruction. Grip and pinch strengths were measured for
      participants in each group both preoperatively and at set postoperative
      intervals. Mean changes in strength were calculated and analysis of variance used
      to determine statistical significance of the changes. Grip strength at 6 weeks
      after surgery in the group that underwent transposition flap repair exceeded
      preoperative grip strength values and all 3 groups surpassed preoperative grip
      strength measurements at 12 weeks. By 6 weeks after surgery, all pinch
      measurements for 3 groups equaled or exceeded preoperative pinch measurements.
      The transposition flap repair group recovered faster than did the other 2 groups
      and surpassed those groups in maximum grip and pinch strength at 12 weeks. These
      results suggest that transverse carpal ligament reconstruction, particularly the
      transposition flap technique, after open carpal tunnel release confers a
      mechanical advantage and that the transverse carpal ligament is an important
      pulley in flexor tendon excursion.

PMID- 9523955
TI  - Electrodiagnostic reports of median neuropathy at the wrist.
AB  - The diagnosis of carpal tunnel syndrome (CTS) is confirmed by electrodiagnostic
      testing. Practice parameters for electrodiagnostic testing of CTS have been
      defined in a summary statement published by the American Academy of Neurology,
      the American Association of Electrodiagnostic Medicine, and the American Academy
      of Physical Medicine and Rehabilitation. All members of the Industrial Injuries
      and Prevention Committee of the American Society for Surgery of the Hand provided
      electrodiagnostic reports from their office practices indicating an
      electrodiagnosis of CTS or median neuropathy at the wrist. One hundred
      consecutive reports were analyzed to determine how often these electrodiagnostic
      studies adhered to the standards and guidelines of the summary statement.
      Variability in the thoroughness of the studies, hence in the quality of
      information in the reports, was noted. The clinical implications of this survey
      are that some patients were diagnosed and treated for CTS who did not have median
      neuropathy at the wrist.

PMID- 9523956
TI  - Patient satisfaction and return to work after endoscopic carpal tunnel surgery.
AB  - One hundred twenty-eight patients with idiopathic carpal tunnel syndrome were
      evaluated before surgery and 3 and 6 months after unilateral endoscopic carpal
      tunnel release. The variables analyzed included patient demographics, symptoms
      and signs, activities of daily living (ADL), sensibility and strength
      measurements, preoperative distal motor latency of the median nerve, operating
      surgeon, postoperative palmar pain and tenderness, return to work, and patient
      satisfaction with the results of surgery. Multivariate statistical analyses were
      performed, with patient satisfaction at 6 months after surgery and the time until
      return to work after surgery as the dependent variables. On stepwise logistic
      regression analysis of all preoperative variables, significant predictors of
      patient dissatisfaction at 6 months after surgery were higher age, heavy
      vibration exposure, worse ADL score, and better distal motor latency. Analysis of
      all preoperative and 3-month postoperative variables showed heavy vibration
      exposure, better distal motor latency, and worse 3-month postoperative ADL score
      to have the strongest independent correlation with patient dissatisfaction at 6
      months. No significant independent association was found between any of the
      preoperative variables studied and the length of time until return to work after
      surgery.

PMID- 9523957
TI  - Recurrent compartment syndrome of the hand: a case report.
AB  - A young man presented with severe symptoms and markedly elevated hand compartment
      pressures 5 weeks after undergoing successful decompressive fasciotomies for
      acute compartment syndrome. The patient's initial postoperative course was
      complicated by reflex sympathetic dystrophy (RSD). It is hypothesized that the
      vasomotor instability and the periodic vasospastic episodes associated with RSD
      prompted postischemic swelling and edema and led to the development of this
      unusual complication.

PMID- 9523958
TI  - Pain responses in patients with upper-extremity disorders.
AB  - The purpose of this study was to evaluate the relationship between pain response
      factors and upper-extremity disorders associated with work-related compensable
      disorders. In this retrospective study, the charts of 113 patients were examined.
      Compensation was not found to have any statistically significant association with
      pain levels. The degree of functional overlay in these patients, indicated by
      pain questionnaire scores, differed only slightly between compensated and
      noncompensated patients and indicated no significant difference between the 2
      groups, except that the compensated group used a higher number of descriptors to
      describe their pain (p = .0143). These results indicate that compensation affects
      the verbalization of pain but does not affect the degree of pain experienced.
      Working status was found to be significantly correlated with a better ability to
      cope with stress at home, suggesting that employment status may be a more
      important factor than compensation status in the presentation of these patients.

PMID- 9523959
TI  - Measurement of the scaphoid humpback deformity using longitudinal computed
      tomography: intra- and interobserver variability using various measurement
      techniques.
AB  - The intra- and interobserver variability of 3 techniques for measuring the
      humpback deformity of 37 scaphoids using longitudinal computed tomography was
      assessed. The 3 measuring techniques were the lateral intrascaphoid angle, the
      dorsal cortical angle, and the height-to-length ratio. The intraobserver
      reliability of the intrascaphoid angle was poor; the dorsal cortical angle was
      moderate to excellent, and the height-to-length ratio was excellent. The
      interobserver reliability of the intrascaphoid angle was poor to moderate, the
      dorsal cortical angle was moderate to excellent, and the height-to-length ratio
      was moderate to excellent. For all 3 observers, the intra- and interobserver
      reliability was the best for the height-to-length ratio and worst for the
      intrascaphoid angle. The height-to-length ratio is the most reproducible method
      of assessing the humpback deformity. Clinical correlation is required to
      establish whether the height-to-length ratio will be of value in predicting the
      outcome of fractures of the scaphoid.

PMID- 9523960
TI  - Triple-injection wrist arthrography: unidirectional communications are due to
      technical factors.
AB  - One justification for triple-injection wrist arthrography is detection of
      unidirectional interjoint communication that might escape notice if only a single
      joint were injected. To determine whether the direction of 1-way communications
      is related to the choice of the first joint injected, the authors prospectively
      randomized 100 wrists undergoing consecutive single-contrast, fluoroscopically
      controlled arthrograms into 2 well-matched groups. One group received the initial
      injections into the midcarpal and distal radioulnar joints and the other group
      received the initial injection into the radiocarpal joint. Two unidirectional
      radial capsular communications with the radiocarpal joint were detected on
      delayed midcarpal joint injection. No other unidirectional communications were
      found. No statistically significant difference was found between the midcarpal
      and radiocarpal study groups. Thus, the first joint injected appears to be a
      major determinant in demonstrating unidirectional communications between wrist
      compartments.

PMID- 9523961
TI  - Injection accuracy and clinical relief of de Quervain's tendinitis.
AB  - In a controlled, prospective, double-blind study, the incidence of accurate
      injection of the abductor pollicis longus (APL) and extensor pollicis brevis
      (EPB) tendon compartments was defined and correlated with clinical relief of de
      Quervain's tendinitis. X-ray dye was included with steroid and lidocaine
      injections for 19 patients; dye location was immediately checked by 1 radiologist
      blinded to the clinical results. Dye was confirmed to be within the first dorsal
      compartment in 16 of 19 cases. There was relief of symptoms in 11 of 19 patients.
      Four of 5 patients with dye in both the APL and EPB tendon compartments,
      experienced relief of symptoms, while all 3 with dye in neither compartment
      experienced no relief. This suggests that accurate injection of steroids is
      required for relief of de Quervain's tendinitis. The EPB compartment was often
      missed (13/19 cases), possibly because it was separate or of small size and deep
      location. This may be a factor in failed injections, just as surgery can fail if
      a separate EPB compartment is not released.

PMID- 9523962
TI  - The effects of multiple-strand suture methods on the strength and excursion of
      repaired intrasynovial flexor tendons: a biomechanical study in dogs.
AB  - This study was designed to determine the effects of in vivo multistrand,
      multigrasp suture techniques on the strength and gliding of repaired
      intrasynovial tendons when controlled passive motion rehabilitation was used.
      Twenty-four adult mongrel dogs were divided into 4 groups and their medial and
      lateral forepaw flexor tendons were transsected and sutured by either the Savage,
      the Tajima, the Kessler, or the recently developed 8-strand suture method. The
      tendon excursion, joint rotation, and tensile properties of the repaired tendons
      were evaluated biomechanically at 3 and 6 weeks after surgery. It was found that
      neither time nor suture method significantly effected proximal and distal
      interphalangeal joint rotation or tendon excursion when the 4 techniques were
      compared to each other. Normalized load value (experimental/control) was
      significantly affected by both the suture method and the amount of time after
      surgery, however. The Savage and 8-strand repair methods had significantly
      greater strength than did the Tajima method at each time interval (p < .05 for
      each comparison). In addition, the 8-strand method had significantly greater
      normalized load values than did the Savage method at each time interval (p < .05
      for each comparison). Normalized stiffness (experimental/control) for the 8
      strand repair method was significantly greater than that for the Tajima and
      Savage methods at 3 and 6 weeks after surgery (p < .05). In addition, the
      normalized stiffness values for the 6-week groups was significantly greater than
      those for the 3-week groups (p < .05). It was concluded that the method of tendon
      suture was a significant variable insofar as the regaining of tendon strength was
      concerned and that the newer low-profile 8-strand repair method significantly
      expands the safety zone for the application of increased in vivo load during the
      early stages of rehabilitation.

PMID- 9523963
TI  - Evidence for muscle attachment at relatively long lengths in tendon transfer
      surgery.
AB  - Sarcomere length was measured intraoperatively during 22 tendon transfers about
      the wrist primarily involving the flexor carpi ulnaris (15), but also including
      the extensor carpi radialis longus (4) and brachioradialis (3). Muscle tension
      during transfer was chosen based on traditional guidelines suggested for optimal
      function. After these criteria were used, it was determined that sarcomere
      lengths were consistently much longer than optimal lengths, even to the point of
      resulting in zero active tension generation. Average sarcomere length after
      transfer was 3.78+/-0.52 microm (mean+/-SD), which was significantly different
      than optimal sarcomere length (2.8 microm) in human skeletal muscle. Muscles were
      predicted to generate on average-on the basis of the 3.78-microm sarcomere length
      only 28% of maximum active force. This appeared to be due to the fact that
      passive tension in upper-extremity skeletal muscles becomes important at only
      relatively long lengths. It is suggested that the use of passive tension as the
      major factor guiding intraoperative decision making results in overstretch of the
      muscle-tendon unit and accompanying low active force generation.

PMID- 9523964
TI  - The lumbrical muscle flap: anatomic study and clinical application.
AB  - This article describes the anatomy and clinical application of the lumbrical
      muscle flap. Anatomic and radiologic studies were performed in 20 fresh human
      cadaver hands injected with latex-lead-oxide solution. Only the 2 radial
      lumbrical muscles were found suitable for flap transposition. The vascular supply
      of the first and second lumbrical muscles is from branches originating in the
      superficial palmar arch and from the common palmar digital artery, respectively.
      The dominant branches invariably enter the muscle bellies at the junction of
      their proximal and middle thirds. Pedicled on these vessels, the lumbrical
      muscles can be transposed to reach the entire palm, up to the wrist flexion
      crease. The clinical use of the first and second lumbrical muscle flaps in 2
      patients demonstrated the value of these flaps for coverage of the median nerve
      and its palmar branches.

PMID- 9523966
TI  - Augmented external fixation of distal radius fractures: a biomechanical analysis.
AB  - An in vitro model of an unstable extra-articular distal radius fracture was
      created in 8 fresh-frozen cadaveric specimens and stabilized with an external
      fixator. Rotation and translation kinematics of the distal radial fracture
      fragment were measured in relation to the proximal radius during physiologic
      loading, using infrared light-emitting diodes and a 3-dimensional motion-sensing
      device. The effect of supplemental single and combination Kirschner wire (K-wire)
      fixation on fracture fragment stability was assessed. Fixation of supplemental K
      wires to the fixator frame via a custom-developed outrigger assembly was also
      analyzed. Significant reductions in sagittal plane (flexion/extension) rotation
      and neutral zone were recorded when the fracture fragment was stabilized with a
      single styloid or dorsal transfixion K-wire. Equivalent stability was afforded by
      attachment of a nontransfixion K-wire to the fixator frame via the outrigger
      assembly. The dorsal constructs compared favorably to the styloid constructs in
      reduction of the sagittal plane neutral zone and coronal (radioulnar) rotation.
      These data lend biomechanical support to the concept of augmentation of distal
      radius external fixation and provide a physiologic model to test fixation methods
      for other fracture patterns.

PMID- 9523965
TI  - Flexor digitorum profundus tendon-to-bone repair: an ex vivo biomechanical
      analysis of 3 pullout suture techniques.
AB  - Avulsions or distal transsections of the flexor digitorum profundus tendon are
      typically repaired by direct suture of tendon to the distal phalanx. The tensile
      properties of tendon-tobone repairs performed in cadaver fingers using 3 common
      suture patterns, the Bunnell, the Kessler, and the Kleinert techniques, were
      compared; 3-0 Prolene (monofilament) suture was used. Repairs done using the
      Kessler pattern had an average yield force of 30 N, compared to 39 N for the
      Bunnell and Kleinert patterns. Although these average yield forces were greater
      than that required for active digital flexion, considerable elongation (average,
      8 mm) was measured at a force of 20 N. Data indicated that the safety factor
      achieved with these repair methods is lower than that achieved with modern tendon
      to-tendon repair methods. The authors conclude that the common tendon-to-bone
      repair techniques are insufficient to withstand the higher forces associated with
      controlled passive and active motion rehabilitation methods that are currently
      advocated.

PMID- 9523967
TI  - Isolated paralysis of the extensor digitorum communis associated with the
      posterior (Thompson) approach to the proximal radius.
AB  - Seven patients presented with an isolated extensor digitorum communis (EDC) palsy
      immediately after undergoing surgery in which the posterior (Thompson) approach
      to the proximal radius was used. All had normal neurologic examination findings
      documented prior to surgery. In an attempt to localize this lesion, the authors
      studied the arborization of the terminal motor branches of the posterior
      interosseous nerve (PIN) at the distal edge of the supinator. A common
      innervation pattern to the superficial extensor muscles was observed in 29 of 30
      cadaveric limbs. In 10 of 10 specimens, when the EDC was subdivided into its
      individual bellies, a reproducible pattern emerged: the proximal EDC muscles of
      the middle and ring fingers were supplied primarily by the recurrent nerve
      branch(es) and the EDC muscles of the index and little fingers, by separate nerve
      branches. Consistent with our anatomic findings, perioperative stimulation of the
      recurrent branch in 1 neurologically intact patient resulted in middle and ring
      finger extension. Electromyography in 8 normal limbs showed that the middle and
      ring fingers could be activated together without the index and little fingers in
      all cases. We believe that these patients with isolated EDC nerve palsy may have
      sustained an iatrogenic injury to EDC motor branches, distal to the supinator
      rather than to a PIN fascicle near the proximal supinator.

PMID- 9523968
TI  - Comparison of the size of plates for fracture fixation with the size of phalanges
      and metacarpals in cadavers of Asian origin.
AB  - The size and volume of plates and screws for fracture fixation of the hand (1.5
      mm screws and titanium miniplates, 2.0-mm screws and stainless-steel AO
      miniplates, and 2.7-mm screws and stainless-steel AO miniplates) were compared
      against the phalanges and metacarpal bones and the surrounding soft tissue from
      male cadavers of Asian decent. In the cadaver study, it was first established
      that the difference between anatomic measurements and radiologic measurements for
      the interarticular bone length and midshaft width were not significant (p = .09).
      Second, the volume occupied by the bone showed a close association to
      interarticular bone length. This finding would suggest that the volume occupied
      by the bone may be estimated from the radiographs. When the length of the plates
      was compared to that of the bones, the analysis showed 4-hole and 6-hole 1.5-mm
      titanium miniplates, and the 4-hole and 6-hole 2.0-mm AO plates were not suitable
      for the middle phalanx, although only rarely are fractures in the middle phalanx
      fixed with plates. For the proximal phalanx, only the 4-hole 1.5-mm and 2.0-mm
      plates were suitable in length. The 6-hole 2.0-mm AO plate was found to be
      suitable for only the longer proximal phalanx of the middle digit. For the
      metacarpals, the 5-hole 2.7-mm AO plate was found not to be suitable for the
      thumb (in length) and the ring digit (in width). The commonly used plates and
      screws for fracture fixation of the hand may not be suitable in size for groups
      of people with smaller hand sizes, in particular some Asians and women.

PMID- 9523969
TI  - Low-velocity gunshot wounds of the proximal phalanx: treatment by early stable
      fixation.
AB  - Twenty-eight proximal phalangeal fractures secondary to low-velocity gunshot
      wounds in 27 patients treated by stable fixation were retrospectively reviewed.
      Definitive fixation was performed within 1 week of injury. Fractures were
      stabilized with either a plate, intramedullary spacer, or a combination of both.
      When necessary, supplemental fixation was achieved with cerclage wires or
      interfragmentary screws. Twenty fractures with bone loss or comminution were
      primarily supplemented with iliac crest bone graft. After surgery, the fingers
      were splinted in 90 degrees of metacarpophalangeal (MP) flexion. An aggressive
      supervised therapy program was initiated within 24 hours of surgery. The average
      length of follow-up care was 9 months (range, 3-29 months). Primary union was
      achieved in all fractures. The average range of motion was 83 degrees for the MP
      joint and 66 degrees for the proximal interphalangeal joint. The average total
      active motion (TAM) for the involved digits was 200 degrees (range, 65 degrees
      250 degrees). Fractures without intra-articular extension had a significantly
      better average TAM (213 degrees) than did those with intra-articular extension
      (169 degrees; p = .05). Primary bone grafting did not adversely effect the final
      TAM. There were no infections. Early stable fracture fixation of these injuries
      achieved union, alignment, and early rehabilitation with no appreciable increase
      in morbidity.

PMID- 9523970
TI  - Coronal fracture of the body of the trapezium: a case report.
AB  - An unusual fracture of the trapezium was found on computed tomography examination
      after plain radiographs failed to demonstrate any bony pathology. This coronal
      fracture has not been previously mentioned in the literature. Management included
      open reduction and internal fixation with 2 lag screws.

PMID- 9523971
TI  - Trapeziolunate external fixation for transscaphoid perilunate dislocations of the
      wrist: report of 2 cases.
AB  - Two transscaphoid perilunate dislocations of the wrist, treated by trapeziolunate
      external fixation--1 after closed and the other after open reduction--are
      reported.

PMID- 9523972
TI  - Distal phalangeal resorption in an adult with infantile malignant osteopetrosis:
      a case report.
AB  - Osteopetrosis is a rare inherited skeletal disorder characterized by a defect in
      bone resorption. The autosomal-recessive infantile malignant form usually results
      in death in the first few years of life. The natural history of the disease into
      adulthood is unknown. Reported here is the case of a 27-year-old man with
      bilateral resorption of the tufts of the distal phalanges in multiple fingers. It
      is unclear whether this finding constitutes a previously undescribed aspect of
      the natural course of the disease or a long-term consequence of therapy.

PMID- 9523973
TI  - Microcirculation of the distal humeral epiphyseal cartilage: implications for
      post-traumatic growth deformities.
AB  - The purpose of this study was to determine if there is an anatomic basis for
      development of the avascular necrosis infrequently seen after elbow trauma. The
      microcirculation to the distal humeral epiphyseal cartilage was studied in 38
      elbow joints from 19 skeletally immature individuals. The findings of this study
      were as follows: (1) Vascularity is centripetal within the epiphyseal cartilages
      of the capitellum, trochlea, and medial and lateral epicondyles. Because of this
      vascularity pattern, it is not easy for avascular necrosis to develop after
      trauma within these epiphyses. (2) Vascularity is longitudinal in the epiphyseal
      cartilage between the capitellum and trochlea. The longitudinal vessels appear
      susceptible to fractures around the elbow in childhood. (3) A rich vascular
      network exists in the olecranon fat pad, and a vascular arch forms from the
      vascular network adjacent to the distal humeral epiphyseal cartilage. The
      vascular arch sends several large branches into the epiphyseal cartilage in a
      vertical fashion. Disruption of either the longitudinal intraosseous vasculature
      (vertical extraosseous blood supply) or the vascular arch in more than 2 places
      may lead to selective avascular necrosis of the epiphyseal cartilage between the
      capitellum and trochlea. These findings suggest vascular compromise as a possible
      explanation for "fish-tail" deformities seen as sequellae of different fracture
      patterns.

PMID- 9523974
TI  - An unusual variation of extensor digitorum brevis manus: a case report and
      literature review.
AB  - An unusual variation of the extensor digitorum brevis manus in a male cadaver is
      presented. The band-shaped muscle was located at the ulnar side of the hand
      between the fourth and fifth extensors. It originated from the deep carpal fascia
      and inserted to the extensor tendons of the fourth and fifth fingers with a
      tendon and a slip, respectively. The origin, insertion, and location of the
      muscle differ from those previously reported; with these anatomic features, the
      muscle variation cannot be placed into the current classifications. The
      phylogenetic and ontogenetic implications of the muscle are reviewed.

PMID- 9523975
TI  - Treatment of subungual myxoma preserving the nail matrix: a case report.
AB  - Subungual myxomas are uncommon, benign, expansile lesions that club the
      fingertip. Traditionally the nail matrix is incised, which results in permanent
      nail deformity. This report describes a midlateral approach that not only spares
      the nail apparatus but demonstrates that the nail can remodel even if a void is
      left under the nail matrix after excision of the tumor. The histologic
      examination of the tumor is described.

PMID- 9523976
TI  - Drug microencapsulation by PLA/PLGA coacervation in the light of thermodynamics.
      1. Overview and theoretical considerations.
AB  - Phase separation of poly(lactide) (PLA) and poly(lactide-co-glycolide) (PLGA),
      often called "coacervation" in the pharmaceutical field, is one of the classical
      methods for peptide drug microencapsulation in biodegradable polyesters. Although
      numerous studies have used this technique, the underlying physicochemical
      mechanisms of polyester coacervation under conditions of microsphere production
      have not been well-described yet. Moreover, the quality of microencapsulation in
      terms of drug loading efficiency and residual organic solvents is often not
      entirely satisfactory and depends greatly on the specific drug and polymer used.
      The first part of this contribution reviews briefly the scientific and patent
      literature on PLA/PLGA coacervation. Then, the underlying physicochemical
      principles of polyester coacervation are discussed and relevant thermodynamic
      models presented. More specifically, attempts were made to clarify the necessary
      characteristics of polymers, solvents, and coacervating and hardening agents for
      successful phase separation and microsphere formation. These basic considerations
      may contribute to a better understanding of the boundary conditions crucial for
      efficient drug microencapsulation by polyester coacervation.

PMID- 9523977
TI  - Drug microencapsulation by PLA/PLGA coacervation in the light of thermodynamics.
      2. Parameters determining microsphere formation.
AB  - Phase separation (frequently called coacervation) of poly(lactide) (PLA) and
      poly(lactide-co-glycolide) (PLGA) is a classical method for drug
      microencapsulation. Here, attempts have been made to describe this process in the
      light of thermodynamics. Different PLA/PLGAs were dissolved in either
      dichloromethane or ethyl acetate, phase separated by addition of the coacervating
      agent silicone oil (PDMS), and hardened in either octamethylcyclotetrasiloxane or
      hexane. Various stages of phase separation were defined microscopically, and the
      coacervate and continuous phases characterized with respect to volume,
      composition, polymer molecular weight, and rheological behavior. The optimal
      amount of PDMS was inversely proportional to the polymer molecular weight and
      hydrophilicity, and a coacervate viscosity of above 5-10 Pa s was required for
      stable coacervate droplets. The composition and, consequently, viscosity of the
      coacervate and continuous phases depended on the polymer-solvent-PDMS
      interactions, as analyzed by the parameters chi (Flory), delta (Hildebrand), and
      delta(int)E (Ho). In general, the lattice model of FIory and Scott describing
      polymer-polymer incompatibility best explained the results. The interaction
      parameters and viscosity of the phases were also helpful to explain microsphere
      characteristics such as residual solvent and particle size. The data suggest that
      microsphere formation by polyester coacervation is primarily driven by molecular
      interactions between polymer, solvents, and coacervating agent.

PMID- 9523978
TI  - Contact allergens from surfactants. Atmospheric oxidation of polyoxyethylene
      alcohols, formation of ethoxylated aldehydes, and their allergenic activity.
AB  - Ethoxylated surfactants are susceptible to oxidation upon air exposure. We have
      previously studied the rate of peroxidation and formaldehyde formation in the
      chemically well-defined ethoxylated alcohol C12H25(OCH2CH2)5OH. Formaldehyde is a
      common cause of contact allergy. The aim of the present study was to identify
      other oxidation products that could be formed upon air exposure of the
      ethoxylated alcohol and to determine their allergenic activity. It was shown that
      air oxidation of C12H25(OCH2CH2)5OH gave all the theoretically possible aldehydes
      of the general formula C12H25(OCH2CH2)nOCH2CHO (n = 0-4) and that the major
      oxidation product was C12H25(OCH2CH2)4OCH2CHO,
      dodecyltetraoxyethyleneoxyacetaldehyde. The structure elucidation and synthesis
      of these aldehydes are here presented for the first time. The major aldehyde was
      shown to be a contact allergen with the same sensitizing capacity as that of
      formaldehyde. A dose-response relationship was observed in the sensitization
      studies. The allergens were formed from the surfactant itself and the skin
      reactions cannot be explained due to any impurities that may be present in a
      technical quality of the surfactant. Cases of allergic contact dermatits to
      ethoxylated surfactants have been reported. To avoid the formation of allergenic
      oxidation products it is important to control the conditions for storage,
      handling, and transportation of ethoxylated surfactants.

PMID- 9523979
TI  - Kinetics of diketopiperazine formation using model peptides.
AB  - The intramolecular aminolysis of Phe-Pro-p-nitroaniline (Phe-Pro-pNA) to Phe-Pro
      diketopiperazine (Phe-Pro-DKP) was studied as a function of pH, temperature,
      buffer concentration, and buffer species using an HPLC assay that permits
      simultaneous analysis of the disappearance of the starting material and the
      appearance of degradation products. The degradation followed pseudo-first-order
      kinetics and showed significant dependence on pH. Phosphate (pH 5-8) and glycine
      (pH 9-10) buffers exhibit general base catalysis. The pH-rate profile suggested
      that the rate of Phe-Pro-DKP formation depends on the degree of ionization of the
      N-terminal amino group, with the unprotonated reactant being more reactive than
      the protonated form. The pKa value of 6.1, determined kinetically, and three
      microscopic rate constants were adequate to describe the shape of the pH-rate
      profile. In the pH range studied, Phe-Pro-DKP was the only product generated upon
      degradation of Phe-Pro-pNA. At pH values between 3 and 8, Phe-Pro-DKP was stable,
      while at pH less than 3 and greater than 8 it undergoes hydrolysis to the
      dipeptide, Phe-Pro-OH. Sequence inversion, a reaction normally associated with
      DKP formation, was not observed. The influence of primary sequence on the
      formation of DKP was also investigated using X-Pro-pNA analogues, where X = Gly,
      Ala, Val, Phe, beta-cyclohexylalanine, and Arg. Changing the amino acid preceding
      the proline residue had a significant effect on the rate of DKP formation at pH
      7.0.

PMID- 9523980
TI  - Pharmacokinetics and metabolism of bisoprolol enantiomers in humans.
AB  - The plasma concentrations and urinary excretions of bisoprolol enantiomers in
      four Japanese male healthy volunteers after a single oral administration of 20 mg
      of racemic bisoprolol were evaluated. The AUC(infinity) and elimination half-life
      of (S)-(-)-bisoprolol were slightly larger than those of (R)-(+)-bisoprolol in
      all subjects. The metabolic clearance of (R)-(+)-bisoprolol was significantly (P
      < 0.05) larger than that of (S)-(-)-bisoprolol (S/R ratio: 0.79+/-0.03), although
      the difference was small. In contrast, no stereoselective in vitro protein
      binding of bisoprolol in human plasma was found. An in vitro metabolic study
      using recombinant human cytochrome P450 (CYP) isoforms indicated that oxidation
      of both bisoprolol enantiomers was catalyzed by the two isoforms, CYP2D6 and
      CYP3A4. CYP2D6 metabolized bisoprolol stereoselectively (R > S), whereas the
      metabolism of bisoprolol by CYP3A4 was not stereoselective. The S/R ratio of the
      mean clearance due to renal tubular secretion was 0.68, indicating a moderate
      degree of stereoselective renal tubular secretion. These findings taken together
      suggest that the small differences in the pharmacokinetics between (S)-(-)- and
      (R)-(+)-bisoprolol are mainly due to the stereoselectivity in the intrinsic
      metabolic clearance by CYP2D6 and renal tubular secretion.

PMID- 9523982
TI  - Functional expression of P-glycoprotein in the hepatic canalicular membrane of
      developing rats.
AB  - P-glycoprotein (P-gp), the multidrug resistance gene product, is expressed in a
      normal liver exclusively on the canalicular membrane of the hepatocyte. The
      objective of this study was to examine the effect of age on the P-gp transport
      system using canalicular membrane (cLPM) vesicles isolated from the liver of
      developing (22 days old) and adult rats. No differences in protein yield,
      intravesicular volumes, and enrichments of cLPM enzymes or enzymes representing
      contamination of subcellular organelles were found for vesicles isolated from
      both groups, demonstrating the isolation of similar cLPM vesicle preparations.
      The transport of daunomycin (DNM), a P-gp substrate, was used to study age
      related functional differences in P-gp. DNM uptake in the presence of ATP was
      greater than uptake in the absence of ATP in both young and adult cLPM vesicles,
      showing that P-gp is functional in both groups. In young and adult groups only
      ATP was a potent stimulator of transport when compared with ATP degradation
      products and a nonhydrolyzable ATP analogue. Although ATP-dependent uptake tended
      to be greater in the adult compared to the young, there was no statistically
      significant difference in DNM kinetics (Vmax, km, gamma) between groups.
      Canalicular membrane from the young rats showed decreased fluidity, as assessed
      by the fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene; however there
      was no significant difference between groups. Examination of P-gp expression
      using the monoclonal antibody C219 revealed similar levels of expression in the
      young as in the adult. Our results suggest that P-gp in the bile canaliculus of
      developing rats is functional with similar levels of function and expression as
      observed in the adult.

PMID- 9523981
TI  - Role of P-glycoprotein as a secretory mechanism in quinidine absorption from rat
      small intestine.
AB  - The intestinal transport of quinidine was characterized in rat small intestine,
      using the Ussing-type chamber under short-circuited conditions. In the short
      circuited condition, quinidine transport was predominantly secretory and the
      transport rate in jejunum was 3.5 times larger in the secretory direction than
      that in the absorptive direction. The secretion of quinidine was found to be
      dependent upon its concentration and to be via a carrier-mediated system in both
      jejunum and ileum. Although the kinetic characteristic of the carrier-mediated
      secretion of quinidine was very similar in jejunum and ileum, its contribution
      was much greater in jejunum because of a higher passive diffusion component in
      ileum. The secretion of quinidine, well-known as an inhibitor of P-glycoprotein,
      was inhibited significantly and its absorption was enhanced significantly by
      several substrates of P-glycoprotein including verapamil, diltiazem, and
      digitoxin in jejunum. These phenomena were also observed by the addition of 2,4
      dinitrophenol. Furthermore, the voltage-clamp studies indicated that the
      inhibition of quinidine secretion occurred in the transcellular pathway. On the
      other hand, neither tetraethylammonium nor p-aminohippuric acid affected the
      transport of quinidine. Quinidine was also recognized to inhibit the secretion
      and to promote the absorption of substrates of P-glycoprotein, chlorpromazine,
      and verapamil. These results strongly suggest that quinidine is not only an
      inhibitor but also a substrate of P-glycoprotein and that the P-glycoprotein
      mediated secretory flux acts as a barrier to quinidine absorption in the small
      intestine, especially jejunum.

PMID- 9523983
TI  - In vitro blood-brain barrier permeability of nevirapine compared to other HIV
      antiretroviral agents.
AB  - To combat infection and inhibit viral replication of HIV in the brain,
      antiretroviral agents must cross the blood-brain barrier (BBB). An in vitro BBB
      model consisting of bovine brain microvessel endothelial cells grown on porous
      filters was used to study and compare the transport of nevirapine, a potent and
      selective nonnucleoside reverse transcriptase inhibitor, with other HIV
      antiretroviral agents currently in use for the treatment of HIV infection. These
      included nucleoside reverse transcriptase inhibitors (didanosine, stavudine,
      zalcitabine, zidovudine), a nonnucleoside reverse transcriptase (delaviridine),
      and protease inhibitors (indinavir, saquinavir, VX-478). Nevirapine was the most
      permeable antiretroviral agent studied in the BBB model. The order of in vitro
      BBB permeability was nevirapine >> VX-478 > didanosine, stavudine, zalcitabine,
      zidovudine > indinavir > saquinavir. There was an apparent bell-shaped
      relationship between in vitro BBB permeability and octanol/phosphate-buffered
      saline distribution coefficient (D) where all lipophilic (log D > 2.5) as well as
      hydrophilic (log D < -0.5) antiretrovirals were less permeable than nevirapine
      (log D = 1.8). There were no significant effects on the in vitro BBB permeability
      of nevirapine in combination with other antiretroviral agents. Saquinavir was the
      only drug shown to have an affinity for the P-glycoprotein efflux pump, which may
      have contributed to its very low permeability. The apparent ability of nevirapine
      to readily permeate the BBB and enter the brain, where it may inhibit replication
      of HIV, potentially increases its therapeutic value.

PMID- 9523984
TI  - Monitoring in situ liver metabolism in rats using microdialysis. Comparison of
      microdialysis mass-transport model predictions to experimental metabolite
      generation data.
AB  - The generation of metabolites from two model compounds, phenacetin and
      acetaminophen, included in the perfusion fluid of a microdialysis probe implanted
      into rat liver was studied. When 60 microM phenacetin was included in the
      perfusion fluid using a flow rate of 1.0 microL/min, acetaminophen and
      acetaminophen sulfate were recovered at concentrations that ranged between 0.4
      and 1.6 microM. Acetaminophen sulfate ([AS]gain) diffused back into the
      microdialysis probe on a micromolar percentage basis of 8.9+/-2.4% (n = 3) when
      acetaminophen was passed through the probe at a concentration between 11 and 12
      microM. When 220-240 microM acetaminophen was passed through the probe, the
      percentage of acetaminophen sulfate recovered was 4.8+/-1.4% (n = 3) (P < 0.1
      compared to the 11 microM group). No acetaminophen glucuronide was detected in
      the dialysate samples. A mathematical model that describes mass transport in
      microdialysis sampling was used to predict the concentration of metabolite that
      could be recovered into the dialysate after the loss of a substrate compound that
      undergoes metabolism. The model predicts a metabolite recovery of 23.6% using
      estimates for phenacetin metabolism and 21.5% using estimates for acetaminophen
      metabolism. The results presented here indicate that microdialysis has potential
      to be used to study local in situ metabolism and with further refinements of the
      microdialysis mass-transport model may be used to estimate in vivo metabolic
      formation rates.

PMID- 9523986
TI  - Improvement of intestinal absorption of peptide drugs by glycosylation: transport
      of tetrapeptide by the sodium ion-dependent D-glucose transporter.
AB  - A tetrapeptide (Gly-Gly-Tyr-Arg, GGYR), which is not transported by di- or
      tripeptide transporters, was glycosylated with p-(succinylamido)phenyl alpha- or
      beta-D-glucopyranoside (alpha,beta-SAPG) to investigate whether these
      glycosylated molecules are transported by the Na+-dependent D-glucose
      transporter. Their uptake into brush border membrane vesicles (BBMVs) and
      transport through the intestinal membrane were examined using the rapid
      filtration technique and the everted sac method. It was observed that
      glycosylation at the alpha-amino position of GGYR increased resistance to
      aminopeptidase activity and inhibited its degradation. When alpha- and beta-SAPG
      GGYR were incubated with BBMVs, overshoot uptake was observed about 2 min after
      the start of incubation in the presence of an inward Na+ gradient. This uptake
      remained unaffected by the addition of GGYR while it was significantly inhibited
      when Na+ was replaced with K+ or alpha- and beta-SAPG-GGYR were incubated with
      BBMVs at 4 degrees C. Uptake was also markedly inhibited either with 1 mM
      phloridzin or 10 mM D-glucose. These findings suggested that the Na+-dependent
      glucose transporter (SGLT-1) played an important role in the uptake of both alpha
      and beta-SAPG-GGYR into BBMVs. A comparison of alpha- with beta-SAPG-GGYR
      revealed that the amount of beta-SAPG-GGYR taken up was greater than that of
      alpha-SAPG-GGYR. From the everted sac method data, it was shown that the
      elimination clearance from the mucosal side, CLel, and permeation clearance to
      the serosal side, CLp, were 15.82+/-6.83 and 0.83+/-0.06 microL/min/cm for alpha
      SAPG-GGYR and 44.52+/-3.61 and 3.50+/-0.81 microL/min/cm for beta-SAPG-GGYR,
      respectively, and that alpha-SAPG-GGYR was more resistant to enzymatic
      degradation than beta-SAPG-GGYR. Permeation of both alpha- and beta-SAPG-GGYR was
      inhibited in the presence of D-glucose and in the absence of a Na+ gradient,
      suggesting that both alpha- and beta-SAPG-GGYR were transported by the Na+
      dependent D-glucose transporter. The permeation clearance transported by the Na+
      dependent D-glucose transporter, (CLp)Na+, of beta-SAPG-GGYR was about 5 times
      greater than that for alpha-SAPG-GGYR. This result may be ascribable to the fact
      that the beta-form of glucose has higher affinity to SGLT-1 than the alpha-form.
      The results of the present study encourage further investigations on improvements
      in intestinal absorption of peptide drugs by glycosylation.

PMID- 9523985
TI  - Intracellular distribution and intracellular dynamics of a spin-labeled analogue
      of doxorubicin fluorescence and EPR spectroscopy.
AB  - Fluorescence spectroscopy revealed a dramatic difference between the
      intracellular distributions of doxorubicin (DOX) and its paramagnetic analogue,
      ruboxyl (Rb). Modification of the anthracyclin structure by introduction of a
      paramagnetic label at position 14 in the DOX molecule resulted in reduced DNA
      binding and enhanced partitioning into phospholipid membranes, as evidenced by
      the fluorescence-quenching experiments. Higher partitioning into cell membranes
      resulted in stronger intracellular fluorescence of Rb. In addition, a
      paramagnetic label on the Rb molecule provided a unique opportunity for an EPR
      investigation of the drug's intracellular distribution and dynamics. The observed
      changes in the EPR spectra of drug-containing cells during their life cycle
      suggested either a progressive release of the intercalated drug, cell membrane
      fluidization, or both.

PMID- 9523987
TI  - Crystal forms of piroxicam pivalate: preparation and characterization of two
      polymorphs.
AB  - This study investigates the polymorphism of piroxicam ester with pivalic acid.
      Two crystal modifications were prepared by recrystallization from toluene (form
      1) and ethyl acetate (form 2). Data regarding preparation conditions, solid state
      properties, and physicochemical characterization of two polymorphs by means of
      FT/IR spectroscopy, X-ray diffractometry on powder, and thermal analysis are
      reported. Heat of fusion rule and thermodynamic formulas consistently indicate an
      enantiotropic stability relationship of forms 1 and 2 with a calculated
      transition point (32 degrees C) near the ambient temperature. The phase diagrams
      of each polymorph with piroxicam were also investigated in order to gain
      information about the thermal behavior of their solid mixtures. Liquidus curves
      calculated by the Schroder-Van Laar equation from fusion enthalpies and
      temperatures were found to agree satisfactorily with experimental results
      obtained by first heating runs with differential scanning calorimetry.

PMID- 9523988
TI  - Transferrin conjugates of doxorubicin: synthesis, characterization, cellular
      uptake, and in vitro efficacy.
AB  - One strategy for improving the antitumor selectivity and toxicity profile of
      antitumor agents is to design drug carrier systems employing suitable carrier
      proteins. Thus, thiolated human serum transferrin was conjugated with four
      maleimide derivatives of doxorubicin that differed in the stability of the
      chemical link between drug and spacer. Of the maleimide derivatives, 3
      maleimidobenzoic or 4-maleimidophenylacetic acid was bound to the 3'-amino
      position of doxorubicin through a benzoyl or phenylacetyl amide bond, and 3
      maleimidobenzoic acid hydrazide or 4-maleimidophenylacetic acid hydrazide was
      bound to the 13-keto position through a benzoyl hydrazone or phenylacetyl
      hydrazone bond. The acid-sensitive transferrin conjugates prepared with the
      carboxylic hydrazone doxorubicin derivatives exhibited an inhibitory efficacy in
      the MDA-MB-468 breast cancer cell line and U937 leukemia cell line comparable to
      that of the free drug (employing the BrdU (5-bromo-2'-deoxyuridine) incorporation
      assay and tritiated thymidine incorporation assay, respectively, IC50
      approximately 0.1-1 mM), whereas conjugates with the amide derivatives showed no
      activity. Furthermore, antiproliferative activity of the most active transferrin
      conjugate (i.e. the conjugate containing a benzoyl hydrazone link) was
      demonstrated in the LXFL 529 lung carcinoma cell line employing a sulforhodamine
      B assay. In contrast to in vitro studies in tumor cells, cell culture experiments
      performed with human endothelial cells (HUVEC) showed that the acid-sensitive
      transferrin conjugates of doxorubicin were significantly less active than free
      doxorubicin (IC50 values approximately 10-40 higher by the BrdU incorporation
      assay), indicating selectivity of the doxorubicin-transferrin conjugates for
      tumor cells. Fluorescence microscopy studies in the MDA-MB-468 breast cancer cell
      showed that free doxorubicin accumulates in the cell nucleus, whereas doxorubicin
      of the transferrin conjugates is found localized primarily in the cytoplasm. The
      differences in the intracellular distribution between transferrin-doxorubicin
      conjugates and doxorubicin were confirmed by laser scanning confocal microscopy
      in LXFL 529 cells after a 24 h incubation that revealed an uptake and mode of
      action other than intercalation with DNA. The relationship between stability,
      cellular uptake, and cytotoxicity of the conjugates is discussed.

PMID- 9523989
TI  - Characterization of the phase transitions of trehalose dihydrate on heating and
      subsequent dehydration.
AB  - Many pharmaceutical compounds of interest form hydrates. The phase behavior of
      different particle size fractions of trehalose dihydrate was studied as the sugar
      was dehydrated by heating. Hot-stage microscopy, X-ray powder diffraction,
      thermogravimetric analysis, and differential scanning calorimetry were used to
      characterize the phase changes. Small particles (<45 microm) formed an amorphous
      phase on dehydration and subsequently liquefied at temperatures above the glass
      transition temperature of amorphous trehalose. Crystallization to the anhydrate
      was observed from this supercooled liquid. Large particles (>425 microm)
      underwent a solid-solid conversion from the dihydrate to the anhydrate at
      temperatures as low as 80 degrees C. This solid-solid conversion was explained by
      a catalytic effect of the liberated dihydrate water on the rearrangement of the
      dehydrated phase to the anhydrate. The large surface area-to-volume ratio of the
      small particles resulted in dehydration prior to attaining the threshold
      temperature for rearrangement, explaining why solid-solid conversion was absent
      for these particles.

PMID- 9523990
TI  - Membrane transport of drugs in different regions of the intestinal tract of the
      rat.
AB  - Regional permeability coefficients of 19 drugs with different physicochemical
      properties were determined using excised segments from three regions of rat
      intestine: jejunum, ileum, and colon. The results are discussed in relation to
      the characteristics of the drug, i.e., MW (range 113-1071 Da), pKa, log D
      (octanol/water at pH 7.4) (range -3.1 to +2.4), and the regional change in the
      properties of the epithelial membrane. There was a significant decrease in
      permeability to hydrophilic drugs and a significant increase in permeability for
      hydrophobic drugs aborally to the small intestine (P < 0.0001). A good
      correlation could be obtained between MW and permeability coefficients of
      hydrophilic drugs. The correlation established between the apparent permeability
      coefficients and the partition coefficients of the drugs was sigmoidal in shape
      in all three regions and a log D between 0 and 2.5 predicts high permeability
      values. These permeability data are unique since they result from a diversity of
      chemical structures with different physicochemical characteristics and a variety
      of transport mechanisms and they are not influenced by interlaboratory
      differences. The large regional permeability database in the present study shows
      the utility of the Ussing chamber technique as a valuable predictive tool for
      human in vivo data. In addition, the regional permeability profiles obtained
      suggest a coupling between drug structure and the functional changes of the
      membrane, which might be useful for selecting a compound for an extended release
      formulation.

PMID- 9523991
TI  - Lipoamino acid conjugates of methotrexate with antitumor activity.
AB  - The synthesis, characterization, and in vitro antitumor activity against a wild
      and a transport-resistant CCRF-CEM cell line is described for a series of
      alpha,gamma-bisamide lipoamino acid and oligomer conjugates of methotrexate. The
      influence of the lipophilicity of the conjugates on the cytotoxicity and the
      dihydrofolate reductase inhibition was investigated. All compounds were more
      active than their fatty acid conjugate analogues. Compound le with a 12-carbon
      atom aliphatic side chain showed the highest in vitro activity.

PMID- 9523992
TI  - Resampling methods in sparse sampling situations in preclinical pharmacokinetic
      studies.
AB  - Toxicokinetic studies often require destructive sampling and the determination of
      drug concentrations in the various organs. Classically, the corresponding
      information is summarized in one mean concentration-time profile, which is
      regarded as representative for the animal population. On the basis of a mean
      profile, only estimates of the secondary pharmacokinetic parameters (for example
      AUC, t1/2) but no variability measures may be obtained. In this paper two
      resampling techniques are contrasted to Bailer's approach. The results obtained
      show that the resampling techniques can be considered a reliable alternative to
      Bailer's approach for the estimation of the standard error of the AUC t(k)0 in
      the case of normally distributed concentration data. They can be extended to the
      estimation of a variety of other secondary pharmacokinetic parameters and their
      respective standard deviations. One disadvantage with Bailer's method is its
      restriction to linear functions of the concentrations. On the other hand, using
      the population approach, prior knowledge of the underlying pharmacokinetic model
      is necessary. The resampling techniques discussed here, the "pseudoprofile-based
      bootstrap" (PpbB) and the "pooled data bootstrap" (PDB), are noncompartmental
      approaches. They are applicable under nonnormal data constellations and permit
      the estimation of the usual secondary pharmacokinetic parameters along with their
      standard deviations, standard errors, and other statistical measures. To assess
      the accuracy, precision, and robustness of the resampling estimators, theoretical
      data from three different pharmacokinetic models with different add-on errors (up
      to 100% variability) were analyzed. Even for the data sets with high variability,
      the parameters calculated with resampling techniques differ not more than 10%
      from the true values. Thus, in the case of data that are not normally distributed
      or when additional secondary pharmacokinetic parameters and their variability are
      to be estimated, the resampling methods are powerful tools in the safety
      assessment in preclinical pharmacokinetics and in toxicokinetics where generally
      sparse data situations are given.

PMID- 9523993
TI  - Determination of binding conformations of drugs to human serum albumin by
      transferred nuclear overhauser effect measurements and conformational analyses
      using high-temperature molecular dynamics calculations.
AB  - The binding conformations of oxyphenbutazone (OXY), Nepsilon-dansyl-L-lysine (DNS
      LYS), and furosemide (FU) to human serum albumin (HSA) have been investigated by
      molecular dynamics (MD) calculations and transferred nuclear Overhauser effect
      (TRNOE) measurements. We have combined distance information obtained from the
      Conformational Analyzer with Molecular Dynamics And Sampling (CAMDAS) calculation
      and experimental NOE spectroscopy measurements to determine a "binding
      conformation" for each drug which binds to site I of HSA. For OXY, only one
      conformer (conf9) among the conformer set generated by MD calculation satisfied
      the distance restraint conditions obtained from TRNOE measurements. For DNS-LYS
      and FU, 17 and 5 conformers satisfied distance restraint conditions,
      respectively. The structure of conf9 of OXY was taken as a "template" to choose
      binding conformers for DNS-LYS and FU. By fitting the "template" to the 17
      conformers of DNS-LYS and 5 conformers of FU, we could efficiently obtain one
      binding conformer for DNS-LYS (conf144) and FU (conf26). It is suggested from the
      feature of the binding conformation that the three-dimensional location of a
      hydrophobic aromatic ring, alkyl chain, and electronegative functional group is
      important for binding to site I of HSA. This method, which combines MD
      calculations and NOE information, is thought to be effective for determining the
      binding conformation of drugs to HSA.

PMID- 9523994
TI  - A method for intratumoral continuous infusion of antisense oligodeoxynucleotides.

PMID- 9523995
TI  - CYP3A4-mediated oxidation of lisofylline to lisofylline 4,5-diol in human liver
      microsomes.
AB  - The cytochrome P450s responsible for the conversion of lisofylline, a drug being
      developed to prevent the complications of high-dose chemotherapy, to lisofylline
      4,5-diol, one of two principal metabolites in human liver microsomes, were
      evaluated. Lisofylline diol formation in microsomes prepared from five adult
      human livers was biphasic, with respective Km values of 0.0230+/-0.015 and 4.23+/
      2.8 mM (mean +/- SD) and respective Vmax values of 0.0565+/-0.052 and 0.429+/
      0.15 nmol/min/mg of protein. Through studies with isoform selective chemical
      inhibitors, CYP3A4 was implicated as the low Km enzyme from 89.0+/-11.2%
      inhibition of lisofylline 4,5-diol formation by troleandomycin at 50 microM
      substrate and CYP2A6 was implicated as the high Km enzyme. The formation of
      lisofylline 4,5-diol by these enzymes was confirmed with cDNA-expressed human
      CYP3A4 and CYP2A6.

PMID- 9523996
TI  - Lag-screw technique in free osseous mandibular reconstruction.
AB  - The surgical registry was reviewed for mandibular reconstruction from 1988 to
      1992. During this time, 51 patients underwent mandibular reconstruction. Of this
      group, 17 patients had their microvascular bone grafts secured with lag-screw
      fixation. An AO technique, utilizing 2.7-mm cortical screws, was used to provide
      rigid fixation. Mandibular defects ranged from 6 to 20 cm. AO vascularized bone
      grafts were studied with bone scans and remained viable. Follow-up revealed no
      flap losses or oral cutaneous fistulae. Lag-screw fixation, in conjunction with
      mandibular reconstruction, results in rigid fixation, obviates the need for
      mandibulamaxillary fixation, has the advantage of ease of application, and is
      safe to use.

PMID- 9523997
TI  - Free vascularized fibular graft in the treatment of Salmonella typhi
      osteomyelitis of the distal radius.
AB  - The authors report a rare case of Salmonella typhi osteomyelitis involving the
      distal radius. The patient was treated successfully by wide resection and
      reconstruction of the distal radius with a vascularized fibular transfer. Local
      recurrence of infection did not occur. The free vascularized fibular graft is an
      effective procedure for the treatment of osteomyelitis of the distal radius.

PMID- 9523998
TI  - Continuous peripheral nerve block in replantation and revascularization.
AB  - Continuous infusion of a local anesthetic by means of a percutaneous forearm
      catheter and an infusion pump was studied for its utility in achieving
      sympathetic blockade following replantation and revascularization of the digits.
      The efficacy of the technique was demonstrated by cold stress testing. When the
      technique was used in 55 patients who underwent digital replantation or
      revascularization, 53 of 57 replanted digits (93 percent) and 25 of 26
      revascularized digits (96 percent) survived. The analgesia obtained from the
      nerve block benefited patient comfort during hospitalization, and normal
      sensibility in the uninjured digits returned promptly after discontinuing the
      anesthetic in all but one patient. The reported study indicates that continuous
      peripheral nerve block by means of an indwelling forearm catheter is a safe and
      effective adjunct in preventing neurogenically-mediated vasospasm.

PMID- 9523999
TI  - Effect of optical temperature feedback control on patency in laser-soldered
      microvascular anastomosis.
AB  - Feedback control has been postulated to improve the efficacy of laser welding in
      microsurgery, but alteration of outcome has not been clearly shown. The authors
      evaluated the ability of an optical closed loop temperature feedback control to
      improve patency, aneurysm rate, and to histologically limit thermal damage. Rat
      femoral artery anastomoses were performed under operating microscope
      magnification. One hundred and twenty-four anastomoses were performed in five
      groups using 1) free-hand (FH) 1.9-microm laser soldering without feedback; 2)
      temperature controlled (TC) 1.9-microm laser soldering with optical feedback; 3)
      FH 808 nm laser; 4) TC 808 nm laser soldering; and 5) 10-0 nylon suture control.
      In Groups 2 and 4, an optical feedback system controlling laser exposure to
      produce a preset temperature was used. Anastomotic time was significantly less
      for all laser groups (p < 0.05). Late patency for all 1.9-microm laser
      anastomoses was almost 0. Temperature controlled 808-nm anastomoses showed no
      significant difference from sutures in terms of patency (88 percent vs. 96
      percent), bursting pressure, and aneurysm rate, while freehand 808-nm anastomoses
      had a significantly lower patency (71 percent) and more tissue damage (ANOVA, p <
      0.05). The authors conclude that temperature control improves outcome in
      microvascular anastomosis by reducing transmural thermal injury caused by
      variations in surgeon technique.

PMID- 9524000
TI  - Successful reinnervation of the penis using an autogenous vein conduit.
AB  - Injury to the dorsal sensory nerve of the penis following penile prosthesis
      insertion is extremely rare. The authors report on a patient with insensitivity
      involving the right penile shaft and glans secondary to entrapment and fibrosis
      of the dorsal cutaneous nerve of the penis, following penile prosthesis
      insertion. Following resection of a 2-cm segment of fibrosed nerve, penile
      sensation was successfully restored using an autogenous vein graft conduit
      between the proximal and distal nerve segments.

PMID- 9524001
TI  - One-stage reconstruction of post-electrical burn forearm and hand defects using
      microsurgical transfer of an ulnar neuromyotendinocutaneous unit.
AB  - Three cases of high-voltage electrical burns of the wrist and forearm were
      reconstructed, using vascularized ipsilateral ulnar nerve transfers to median
      nerve defects. Two of these cases utilized composite ulnar neuromyotendinous flap
      transfers, with the muscle (flexor carpi ulnaris) bridging the gap between the
      flexor muscle bellies and tendons. Sensory recovery in the hand was excellent in
      all three cases.

PMID- 9524002
TI  - The lateral arm flap: review of 72 cases and technical refinements.
AB  - Between 1985 and 1995, 72 free lateral arm flaps (LAFs) were transferred in 68
      patients. The main purpose of the reported study was to demonstrate a
      comprehensive follow-up and essential technical refinements: extension of the
      flap, shaping of a custom-designed flap, the "emergency" free flap, and sensible
      nerve coaptation. The effect of nerve coaptation vs. no nerve coaptation was
      investigated by measuring objective and subjective grades of sensibility at the
      recipient site. The outcomes of sensory flap reinnervation showed no significant
      advantages of one over the other technique. The second intention was to clarify
      discrepant anatomic descriptions concerning the nomenclature of the supplying
      blood vessels. Current anatomic investigations revealed that the main blood
      supply derives from the posterior radial collateral artery (anastomosing with the
      interosseous recurrent artery); blood supply via the anterior radial recurrent
      artery (anastomosing with the radial recurrent artery) has a secondary
      importance.

PMID- 9524003
TI  - Free groin flap for reconstruction of the tongue and oral floor.
AB  - The authors report the use of free groin flaps to close intraoral defects in 24
      patients following ablative tongue cancer surgery. The lateral thin portion of
      the flap was used for tongue reconstruction, and the deepithelialized medial
      thick portion for filling the mandibular defect and for covering the important
      vessels in the neck. In lean patients, if the medial deepithelialized portion was
      too thin for adequate coverage, the proximal sartorius muscle was included to
      prevent postoperative orocervical fistula. The advantages of the groin flap in
      reconstructing the tongue and oral floor after hemiglossectomy include the
      following: (1) a suitable amount of tissue is available for both the tongue and
      oral floor; (2) the important vessels in the neck may be protected with the flap;
      (3) the proximal sartorius muscle can be included with the flap, if necessary;
      (4) donor-site morbidity is less than with other flaps; and (5) flap elevation
      can be done concurrently with the hemiglossectomy and radical neck dissection.

PMID- 9524005
TI  - Monitoring spinal-cord injury intraoperatively and attempting prognosis by
      cortical somatosensory evoked potentials: experimental study.
AB  - In order to monitor spinal-cord injury intraoperatively and to evaluate prognosis
      by cortical somatosensory evoked potentials (CSEP), the spinal-cord function of
      42 dogs, whose cords were injured by air-sac pressure or various striking trauma,
      was monitored by CSEP intraoperatively and 1 to 3 months postoperatively.
      Although amplitude declined by 100 percent, compared with preoperative readings,
      spinal-cord injury by air-sac pressure had no lasting effects. If the pressure
      was removed in a timely fashion, the function of the spinal cord recovered after
      1 to 3 months postoperatively. As for the effect of various striking traumas,
      safe limits, according to intraoperative CSEP monitoring, were that the prolonged
      P1 wave latency was less than 1.5 times, and that the declining P1-N1 wave
      amplitude was less than 50 percent. The change in amplitude was quite sensitive
      and its recovery was earlier than morphologic changes and functional recovery.
      Results indicated that CSEP monitoring of spinal-cord injury intraoperatively is
      accurate and reliable and that it can also predict an accurate prognosis for the
      injured spinal cord in this canine model.

PMID- 9524004
TI  - Long-term functional results of contralateral C7 transfer.
AB  - From 1986 to 1994, 82 patients with brachial plexus root avulsion were operated
      on using a contralateral C7 nerve-root transfer. Forty-four patients underwent a
      one-stage procedure in which the distal end of the ulnar nerve was anastomosed to
      the contralateral C7 root, and the other 38 underwent a two-stage procedure
      (first phase: C7 root --> ulnar nerve; second phase: ulnar nerve --> recipient
      nerve). Twenty postoperative cases were followed-up for 2 years. Of them, the
      ulnar nerve was transferred to the musculocutaneous nerve in six cases, with
      recovery of the biceps up to M3 in four and S3 in five cases; the ulnar nerve was
      transferred to the median nerve in eight cases, with recovery of the wrist and
      finger flexors up to M3 in five and S3 in six cases; the ulnar nerve was
      transferred to the radial nerve in four cases, with recovery of the triceps up to
      M4 in two and S3 in three cases; and the ulnar nerve was transferred to the
      thoracodorsal nerve in two cases, with recovery of the latissimus dorsi to M4 in
      one case. The total muscle recovery rate (up to M3) of the series was 60 percent,
      and the sensory recovery rate (S3) was 78 percent. Outcomes were related to
      patient age, operative delay, and whether or not the ulnar nerve was used as a
      bridge for transfer.

PMID- 9524006
TI  - A method for prevention of arterialized venous flap necrosis.
AB  - The authors used a delayed arteriovenous (A-V) shunt method to prevent congestion
      and necrosis of arterialized venous flaps. Two weeks before elevating the flap,
      an A-V shunt between the central artery and vein was created at the more proximal
      flap end. Twelve rabbits (24 flaps) were used for this experiment. Flaps were
      followed for 4 weeks. Twelve of 24 flaps survived completely; another 10 flaps
      showed partial necrosis; and two flaps became completely necrotic. These results
      demonstrated that this method is superior to a simple A-V shunt in preventing
      congestion and necrosis in the arterialized venous flap.

PMID- 9524007
TI  - Bacterial endocarditis at a tertiary hospital--how do we improve diagnosis and
      delay of treatment? A retrospective study of 140 patients.
AB  - During a period of 3.5 years, endocarditis was suspected in 151 patients admitted
      to Rigshospitalet. 140 were available for this study. In 59 of the 140 patients,
      the diagnosis was confirmed, and 36 had positive blood cultures.
      Echocardiographic findings compatible with the diagnosis were present in 92% of
      the 59 cases. The most common causes of endocarditis were Staphylococcus aureus
      and viridans streptococci. Patients with endocarditis caused by S. aureus had
      significantly (p = 0.002) more embolic episodes compared to patients having
      endocarditis caused by the viridans streptococci. The diagnosis was established
      at a mean of 3-4 weeks after the onset of symptoms and 2 weeks after admission to
      hospital. In order to minimize diagnostic delay, the following aspects may be
      important: (1) earlier detection of endocarditis among physicians examining
      patients at risk; (2) educating patients with cardiac disease and cardiac valve
      prosthesis; (3) earlier antibiotic therapy, and (4) developing further
      diagnostics for endocarditis.

PMID- 9524008
TI  - Effects on heart rate variability of isosorbide-5-mononitrate and metoprolol in
      patients with recent onset of angina pectoris.
AB  - BACKGROUND: Beta-blockers reduce sympathetic tone, increase vagal tone and
      improve prognosis in ischaemic heart disease. Nitroglycerin, being a vasodilator,
      may theoretically have an opposite effect and worsen the prognosis. The purpose
      of the present study was to analyse heart rate variability (HRV), which reflects
      autonomic tone, in angina patients on isosorbide-5-mononitrate (IS-5-MN) and/or
      metoprolol. METHODS AND RESULTS: Thirty-two patients (32-81 years old), with
      recently developed angina (median duration: 3 months), showing no other disease
      and on no drugs, were Holter-monitored 24-48 h at baseline and after 4-5 days on
      IS-5-MN (mean daily dose: 33 mg), on metoprolol (mean daily dose: 184 mg) and on
      the combined treatment. Recordings were analysed on the Marquette Series 8000
      Holter scanner. Both IS-5-MN and metoprolol significantly reduced myocardial
      ischaemia (ST integral) and ventricular tachycardias. Metoprolol induced
      significant changes in the following parameters (baseline versus metoprolol):
      high-frequency peak 9 +/- 4 versus 11 +/- 4 ms (p < 0.001), low-to-high frequency
      ratio 2.5 +/- 0.6 versus 1.9 +/- 0.6 (p < 0.0001), root mean square of RR
      interval difference 23 +/- 7 versus 31 +/- 9 ms (p < 0.0001), RR intervals
      differing more than 50 ms from the preceding one 4.8 +/- 3.9 versus 10.0 +/- 7.0%
      (p < 0.0001), mean of all 5-min standard deviations 50 +/- 12 versus 56 +/- 11 ms
      (p < 0.001) and mean RR interval 819 +/- 90 versus 1,019 +/- 120 ms (p <
      0.00001). The combined treatment caused approximately the same HRV changes as
      metoprolol alone. IS-5-MN had no significant effect on any HRV parameter, neither
      alone nor in combination with metoprolol. CONCLUSION: A clinically effective dose
      of metoprolol had potentially positive effects on HRV with increase in vagal and
      decrease in sympathetic tone while IS-5-MN had no effect on HRV, neither positive
      nor negative, neither alone nor in combination with metoprolol.

PMID- 9524009
TI  - Use of fish oils appears to reduce infarct size as estimated from peak creatine
      kinase and lactate dehydrogenase activities.
AB  - In 753 patients with acute myocardial infarction, use of fish oils (FO, n = 242)
      before onset of infarction seemed to reduce infarct size as estimated from peak
      creatine kinase (CKmax) and lactate dehydrogenase (LDmax) activities. The study
      had an observational exposed/nonexposed design, and both crude and adjusted
      effects were looked for. CRUDE EFFECTS: In the restricted cohort of patients not
      receiving thrombolytic treatment (n = 411), FO reduced CKmax from 879 to 759 U/l
      (2 p = 0.030) and LDmax from 870 to 768 U/l (2 p = 0.011), respectively. More of
      these patients in the lowest enzyme quartiles used FO, p for linear trend was for
      CKmax 0.008 and for LDmax 0.06, respectively. ADJUSTED EFFECTS: In patients not
      receiving thrombolytic treatment, FO reduced CKmax (2 p = 0.007) and LDmax (2 p =
      0.005), but in patients receiving such treatment, CKmax and LDmax values
      increased, 2 p being 0.036 and 0.097, respectively. In patients not receiving
      thrombolysis, FO increased the incidence of small infarcts (the 25% quartile),
      odds ratio for CKmax was 1.82 (2 p = 0.018) and for LDmax 1.66 (2 p = 0.048),
      respectively. The results indicate that FO may reduce infarct size and the
      incidence of large infarcts. In addition, FO seems to enhance the effect of
      thrombolysis.

PMID- 9524010
TI  - Diffuse narrowing of coronary arteries in diabetic patients: the earliest phase
      of coronary artery disease.
AB  - Coronary arteries in diabetic patients appear to be narrower than in normal
      subjects, but this has not been examined systematically. To investigate this
      hypothesis we reviewed the data of 711 consecutive patients with angiographically
      'normal coronary arteries'. Excluded were patients with valvular, myocardial or
      pericardial disease, and patients with hypertension or hyperlipidemia. Thirteen
      diabetic patients (10 men) and 22 nondiabetic persons (8 men) constituted the
      study and control groups, respectively. The diameters of the coronary arteries
      and their branches were measured and adjusted for body surface area. The sum of
      the proximal left anterior descending (LAD), circumflex and right coronary
      arteries (RCA) was calculated and defined as total coronary diameter (TCD). The
      sum of the distal LAD, first diagonal, first marginal and distal RCA was
      calculated and defined as total distal coronary diameter (dTCD). The clinical
      data of both groups were comparable. Adjusted TCD for body surface area was 5.4
      +/- 1.1 and 6.5 +/- 1.1 mm/m2 (p < 0.05) in diabetics and nondiabetics,
      respectively, and adjusted dTCD was 4.9 +/- 1.2 and 6.1 +/- 1.2 mm/m2 (p = 0.01)
      in diabetics and normal subjects, respectively. Specific arteries and branches
      that were significantly smaller in diabetics included: left main coronary artery,
      distal LAD, first diagonal, proximal RCA, distal RCA, right ventricular branch,
      and posterolateral and posterior descending artery of RCA origin. Gender was not
      a confounding factor since the control group had a larger proportion of women and
      still larger arteries than the diabetic group. In conclusion, coronary arteries
      and their branches in diabetic patients have smaller diameters than normal
      subjects. This may be due to increased coronary tone, diffuse mild
      atherosclerosis or both.

PMID- 9524011
TI  - The effects of antihypertensive agents on atherosclerosis-related parameters of
      human aorta intimal cells.
AB  - Four antihypertensive agents - amlodipine, verapamil, propranolol and
      perindoprilat - were studied in human cell cultures. Antiatherogenic activity was
      investigated using uninvolved human aortic smooth muscle intima cells and
      atherogenic serum obtained from patients with coronary atherosclerosis.
      Amlodipine and verapamil significantly inhibited serum-induced increases in
      cholesterol content, cell-proliferative activity and protein synthesis in the
      cultured cells. Propranolol increased all three parameters, while perindoprilat
      had no effects. In addition, amlodipine and verapamil significantly lowered the
      intracellular cholesterol content of smooth muscle cells derived from
      atherosclerotic plaque and inhibited cell proliferation and protein synthesis.
      Propranolol increased all of these parameters, while perindoprilat produced no
      effects. The antiatherogenic and antiatherosclerotic actions of verapamil and
      amlodipine were confirmed in an ex vivo model. These studies demonstrated a
      beneficial antiatherosclerotic effect of amlodipine that was greater than that of
      verapamil. Perindoprilat had a neutral effect on atherosclerotic parameters,
      while the action of propranolol appeared to be potentially detrimental.

PMID- 9524012
TI  - Mechanism of antiarrhythmic effects of class Ic drugs in paroxysmal atrial
      fibrillation in man.
AB  - While class Ic antiarrhythmic drugs are effective in treating patients with
      atrial fibrillation, their mechanism of action is poorly understood. We performed
      electrophysiological studies before and after their administration to 22 patients
      with paroxysmal atrial fibrillation. Atrial refractoriness, maximal interatrial
      conduction delay and the wavelength index were measured at two basic cycle
      lengths (600 or 400 ms). Both drugs studied increased atrial refractoriness and
      wavelength index. Flecainide reduced the maximal interatrial conduction delay,
      but pilsicainide did not. Each drug increased the wavelength index in a
      tachycardia-dependent manner. Class Ic drugs may reduce atrial vulnerability by
      increasing the wavelength of the reentrant circuit during periods of rapid heart
      rate.

PMID- 9524013
TI  - Lipid peroxidation and cardiac troponin T release during routine cardiac surgery.
AB  - Myocardial injury after cardiac surgery with cardiopulmonary bypass may be
      related to free oxygen radical-induced lipid peroxidation. The purpose of this
      study was to monitor perioperative changes of cardiac troponin t and
      malondialdehyde as an indicator of lipid peroxidation in patients who underwent
      routine cardiac operation and had no signs of perioperative myocardial
      infarction. Patients with thoracic surgery alone served as controls. We studied
      20 patients with cardiopulmonary bypass (CPB) and 9 patients with other thoracic
      operations. Serum troponin t, malondialdehyde, myoglobin, creatine kinase (CK)
      including CK-MB isoenzyme levels were monitored before CPB, immediately after
      cessation of CPB, 20 and 44 h after CPB. Patients with signs of myocardial
      infarction before or up to 44 h after surgery were excluded. Of 20 patients with
      CBP, 18 patients showed a significant increase of troponin t and 16 patients had
      elevated malondialdehyde serum levels following CPB. Troponin t serum values were
      raised immediately after CPB to 0.60 +/- 0.12 microg/l and increased further to
      0.90 +/- 0.17 microg/l after 44 h (p < 0.005, in comparison to preoperative: 0.08
      +/- 0.02 microg/l). Patients undergoing the other thoracic operations showed
      neither any detectable troponin t serum values nor significant changes of serum
      malondialdehyde during the observed period. In the CPB group serum
      malondialdehyde peaked immediately after CPB to 98 +/- 9 nmol/g albumin (p <
      0.005) and returned to preoperative levels (63 +/- 3 nmol/g albumin) within 20 h
      (60 +/- 3 nmol/g albumin). Individual maximal troponin t serum levels did not
      correlate with individual maximal serum malondialdehyde levels. The observed
      increase of troponin t levels had no influence on patients' outcome followed up
      for 18 months. The results demonstrate that troponin t and lipid peroxidation
      increase during uncomplicated cardiac surgery in patients without signs of
      myocardial infarction. Following uncomplicated cardiac surgery, a moderate
      increase of cardiac troponin t may not reflect severe cardiac injury.

PMID- 9524014
TI  - Therapeutic benefits of cilazapril in patients with syndrome X.
AB  - OBJECTIVES: Although the pathophysiology of syndrome X (angina pectoris, positive
      ECG test findings and normal coronary arteriogram) is unclear, it is generally
      accepted that intracellular metabolic changes resulting from abnormal
      constriction of prearteriolar vessels due to endothelium-dependent vasodilation
      abnormalities may play a role in the pathogenesis. We established the effect of
      long-term treatment with cilazapril, an angiotensin-converting enzyme inhibitor,
      which prevents the effect of angiotensin II in the tonic control of vascular
      resistance. METHODS: 18 patients (15 women and 3 men, mean age 43.2 +/- 4.6
      years) with syndrome X were included in this study. A randomized double-blind
      crossover placebo-controlled trial was done. After a 1-week washout period,
      patients received either cilazapril 2 x 2.5 mg or placebo for 3 weeks, followed
      by 3 weeks of the other therapy. At the end of two periods, an exercise ECG test
      (modified Bruce protocol) was employed. RESULTS: The magnitude of ST segment
      depression was significantly decreased during treatment with cilazapril compared
      with placebo. On the other hand, total exercise time and time to 1 mm ST segment
      depression were significantly prolonged by cilazapril. However, rate pressure
      products were not significantly different at peak exercise at or at 1 mm of ST
      segment depression during both therapies. CONCLUSION: Cilazapril exerted a
      beneficial therapeutic effect in cases with syndrome X. The possible mechanism of
      this effect may be a modulation of coronary tone at the microcirculation level.

PMID- 9524015
TI  - Morphological characterization of ventricular septal defect with posterior
      deviation of the outlet septum.
AB  - Ventricular septal defect (VSD) with posterior deviation of the outlet septum is
      frequently associated with left ventricular outflow obstruction and aortic arch
      anomalies. In this study, 17 patients with large VSD and posterior deviation of
      the outlet septum were evaluated. The VSD was further classified into 'high' and
      'low' types according to the extension of the VSD; the high-type VSD (8 patients)
      extended mainly to the outlet or infundibular portion and the low-type VSD (9
      patients) extended mainly to the trabecular or inlet portion. Related
      morphological features, such as outlet septum hypoplasia, muscle bundle between
      aortic-mitral valve junction, pulmonary artery overriding and aortic arch
      anomalies, were found more frequently in patients with high-type VSD, while
      tricuspid valve straddling and outlet septum hypertrophy were found more often in
      patients with low-type VSD. This classification for VSD with posterior deviation
      of the outlet septum helps to predict the morphological features of left
      ventricular outflow tract and aortic arch anomalies.

PMID- 9524016
TI  - Dynamic three-dimensional echocardiography using parallel slicing: a promising
      diagnostic procedure in adults with congenital heart disease.
AB  - In 18 of 77 adult patients presenting with congenital heart disease, three
      dimensional conceptualization was found to be insufficient using two-dimensional
      echocardiographic imaging. In these individuals, three-dimensional image
      reconstruction from digitized parallel images was carried out, providing
      additional information in 14 of them. Three-dimensional echocardiography and
      volumetry may, especially in patients with atrial septal defect, cor triatriatum
      and corrected transposition of the great arteries, be an asset amplifying the
      diagnostic information yielded by conventional two-dimensional echocardiographic
      approaches.

PMID- 9524017
TI  - Diagnosis and management of partial anomalous pulmonary venous connection. A
      review of 28 pediatric cases.
AB  - Medical records, angiograms and operative records of 28 patients with partial
      anomalous pulmonary venous connection (PAPVC) were reviewed. Twenty patients had
      one anomalous pulmonary vein (APV), and 8 had more than two APVs. Twenty-five
      patients (89%) had APVs originating from the right lung, 2 (7%) from the left
      lung and 1 (4%) from both lungs. In the 25 patients with APVs originating from
      the right lung, 9 had APVs draining into the superior vena cava (SVC), 13 into
      the right atrium (RA), 1 into the inferior vena cava (IVC) and 2 into both the
      SVC and RA. In the 2 patients with APVs originating from the left lung, 1 had
      APVs draining into the RA, and the other had APVs draining into the innominate
      vein. The patient with APVs originating from both lungs had connection to the
      IVC. Twenty-three patients (82%) had additional cardiovascular defects. Surgery
      was performed in 13 patients who had pulmonary/systemic flow ratios greater than
      2.0. The patients have done well after surgery. In 7 patients, we were unable to
      accurately determine the number or sites of drainage of APVs prior to surgery. We
      conclude that selective pulmonary angiography is indispensable for the accurate
      diagnosis of PAPVC.

PMID- 9524018
TI  - Differences in transmitral flow velocity pattern during increase in preload in
      patients with abnormal left ventricular relaxation.
AB  - Changes in transmitral flow (TMF) and pulmonary venous flow (PVF) velocities
      during increases in preload were compared in patients with a higher peak atrial
      systolic velocity than peak early diastolic velocity (A/E > 1) for the TMF
      velocity to determine differences in hemodynamic response. Fifteen patients with
      dilated hearts, 22 with hypertrophied hearts and 15 control patients were
      studied. TMF and PVF velocities were recorded by transesophageal pulsed Doppler
      echocardiography before and during application of lower body positive pressure.
      The value for peak early diastolic velocity increased, while the isovolumic
      relaxation time decreased with increases in preload in all groups. The value for
      peak atrial systolic velocity decreased in the dilated-heart group, but increased
      in the hypertrophied-heart and control groups. The peak second systolic and early
      diastolic PVF velocities increased in the dilated- and hypertrophied-heart
      groups, but did not change in the control group. The peak atrial systolic PVF
      velocity and the difference in duration of the atrial systolic PVF and TMF
      velocities increased in the dilated- and hypertrophied-heart groups, and its
      changing rate was highest in the group with dilated hearts. These results suggest
      that both peak early diastolic and atrial systolic TMF velocities increase during
      increases in preload through the Frank-Starling mechanism in hypertrophied
      hearts. Furthermore, the left ventricular functional reserve was lower in the
      dilated-heart group. Thus, TMF and PVF velocities respond differently during
      increases in preload, depending on the underlying heart disease.

PMID- 9524019
TI  - Pseudo-pseudoaneurysm of the left ventricle.
AB  - Left ventricular pseudoaneurysms are an uncommon complication of myocardial
      infarction and need urgent surgical repair. Though it is critical that they be
      accurately identified, pseudoaneurysms are occasionally misdiagnosed. We report
      an abnormality which may be mislabeled a pseudoaneurysm which we term a pseudo
      pseudoaneurysm. The approach to accurate diagnosis of pseudoaneurysms is
      discussed.

PMID- 9524020
TI  - Effect of the balloon-to-anulus ratio on pulmonary balloon valvuloplasty.

PMID- 9524021
TI  - Acute coronary syndromes.

PMID- 9524022
TI  - Glaucoma surgery, statistics and the mini-skirt.

PMID- 9524023
TI  - The conundrum of endophthalmitis.

PMID- 9524024
TI  - Patterns of peri-operative prophylaxis for cataract surgery: a survey of
      Australian ophthalmologists.
AB  - BACKGROUND: Although peri-operative prophylaxis to prevent endophthalmitis is
      commonly practised by ophthalmologists, no one method has clearly been
      demonstrated to be more effective than another. We surveyed 570 Fellows of the
      Royal Australian College of Ophthalmologists to determine what their methods of
      prophylaxis were and whether these differed for patients who developed
      endophthalmitis. METHODS: The questionnaire asked about the types of antibiotics
      and other methods of prophylaxis used before, during and after cataract surgery.
      Of those who reported cases of endophthalmitis, we asked specifically about the
      methods of prophylaxis used for those patients. RESULTS: The response was 89% and
      the incidence of endophthalmitis was calculated as 0.11%. There was little
      difference in the methods of prophylaxis used by those who reported
      endophthalmitis compared with others, but pre-operative antibiotics were used
      more commonly by those who reported the disease (P = 0.06). Surgeons who had
      practised for 20 years or more reported a lower rate of endophthalmitis than
      others, as did those who performed more than 300 cataract operations per year.
      However the pattern of prophylaxis used by these two sub-groups was quite
      divergent. Differences in the methods of prophylaxis had no bearing on the
      development of endophthalmitis, with the exception that subconjunctival
      antibiotics were used less often in those patients who developed the disease (P =
      0.03). CONCLUSIONS: The results of the present study provide no clear answer
      regarding appropriate peri-operative prophylaxis. The wide range of prophylactic
      regimens used suggests that no one method is superior to another. Formal case
      controlled studies are required to identify which method would be most
      efficacious.

PMID- 9524025
TI  - Extracapsular cataract surgery in Vietnam: a 1 year follow-up study.
AB  - PURPOSE: Unoperated cataract is the leading cause of blindness in the developing
      world. Many developing countries now use extracapsular cataract extraction (ECCE)
      with intra-ocular lens insertion (IOL) in their cataract blindness-prevention
      programmes. To date, little research has been directed at visual outcomes and
      complication rates of ECCE/IOL surgery in developing countries. METHODS: We
      conducted a follow-up study of 155 eyes approximately 12 months after ECCE/IOL
      surgery by eight local eye surgeons in Central Vietnam. We report the findings
      for the 144 eyes (93%) successfully reviewed. All subjects underwent manual ECCE
      with insertion of a three-piece posterior chamber IOL. All eyes were also
      assessed for the presence and severity of posterior capsule opacification (PCO)
      using a newly developed grading system. RESULTS: Overall, 110 eyes (75%) had
      uncorrected visual acuities > or = 6/24 and 107 eyes (74%) had best spherically
      corrected visual acuities > or = 6/18. Some degree of PCO was found in 40% of
      eyes, but was graded as visually significant in only 4% of eyes. No major sight
      threatening complications were noted. A portable neodymium:yttrium aluminium
      garnet (Nd:YAG) laser was used to perform capsulotomies on all eyes with visually
      significant PCO. There were no laser complications noted. CONCLUSIONS: At
      approximately 1 year after ECCE/IOL, the visual outcomes for subjects in this
      cohort were favourable and complication rates were low. Posterior chamber
      opacification was not a major cause of vision impairment in this cohort. Portable
      Nd:YAG lasers may provide an effective solution to the problem of visually
      significant PCO occurring in developing countries as a late complication of
      extracapsular surgery. These findings support an increasing role for ECCE/PCIOL
      surgery by trained local eye surgeons in developing countries.

PMID- 9524026
TI  - Comparison of extracapsular and phaco-emulsification cataract extraction
      techniques when combined with intra-ocular lens placement and trabeculectomy:
      short-term results.
AB  - BACKGROUND METHODS: Fifty patients who had undergone combined extracapsular
      cataract extraction (ECCE), intra-ocular lens (IOL) placement and trabeculectomy
      (ECCE-trab) and 50 who had undergone combined cataract phaco-emulsification, IOL
      placement and trabeculectomy (phaco-trab) were reviewed over a period of 12
      months. RESULTS: Postoperatively, intra-ocular pressure (IOP) in both eyes fell
      significantly (P < 0.005). Initially, IOP fell to roughly equal degrees (mean IOP
      being 14 mmHg at 3 months; P = 0.84). At 12 months, IOP in the phacotrab group
      was slightly lower than that in the ECCE-trab group (13.4+/-4.3 vs 15.4+/-4.4
      mmHg, respectively; P = 0.0312). The number of pre-operative medications did not
      appear to affect outcome (P = 0.124). Visual recovery was approximately 3 months
      faster in the phaco-trab group. By 12 months there was little difference in
      visual acuity, with an average improvement of two Snellen lines (P = 0.68). The
      mean change in astigmatism was significantly less in the phaco-trab group (0.61+/
      1.25 vs 1.39+/-1.46 D, respectively, P = 0.0063). Transient hypotony (IOP < 5
      mmHg) was more frequent in the phaco-trab group (66 vs 32%, respectively; P <
      0.002). The frequency of other complications was not significantly different
      between the two groups. CONCLUSION: Both ECCE-trab and phaco-trab procedures are
      safe and effective. However, the phaco-trab procedure may have slightly improved
      IOP control, earlier visual recovery and less astigmatism.

PMID- 9524027
TI  - The snapped inferior rectus.
AB  - PURPOSE: To evaluate the management and possible aetiology of the snapped
      inferior rectus muscle in strabismus surgery. METHODS: Three patients are
      described whose inferior rectus muscle broke across its width some 8-10mm behind
      the insertion while being held on a squint hook without excessive force during
      strabismus surgery. The proximal part of the muscle was not found. The distal
      part of the snapped muscle was excised for pathological examination.
      Transposition of the inferior halves of the adjacent horizontal muscles to the
      insertion of the inferior rectus (a modified inverse-Knapp procedure) was
      performed in all cases. RESULTS: After the transposition surgery, one patient was
      orthotropic in the primary position, one patient required a prism correction to
      produce a range of single vision and the third patient was orthotropic after a
      further operation. There was good depression in one case and the other two had a
      limitation of depression. In all cases, horizontal movements remained intact and
      there were no signs of anterior segment ischaemia. CONCLUSIONS: The unique
      relations of the inferior rectus to the surrounding tissues may be a factor in
      causing the breaking of this muscle. Two of the patients were elderly and this
      may be a factor also. Transposition surgery is the appropriate management when
      the proximal part of the snapped muscle cannot be located and has satisfactory
      but imperfect results.

PMID- 9524028
TI  - External argon laser choroidotomy for subretinal fluid drainage.
AB  - PURPOSE: To evaluate the efficacy and safety of external argon laser choroidotomy
      for drainage of subretinal fluid (SRF) during scleral buckling procedures for the
      repair of rhegmatogenous retinal detachments. METHODS: Fifty eyes of 50
      consecutive patients presenting to a hospital-based retinal outpatient clinic
      with rhegmatogenous detachments underwent choroidotomy with argon endolaser for
      SRF drainage. The laser parameters used were 0.5s duration and 0.8W power. The
      primary outcome measures were successful drainage of SRF and incidence of
      complications. The drainage was considered successful if it was sufficient to
      complete the planned scleral buckling procedure. The extent of subretinal
      haemorrhage was graded. RESULTS: The mean age of patients was 55 years (range 16
      80 years). Successful drainage of SRF was obtained in 47 eyes (94%). The
      complications observed at the drainage site included subretinal haemorrhage of
      less than 1 disc diameter in six eyes (12%) and retinal perforation in one eye
      (2%). CONCLUSION: External argon laser choroidotomy appears to be an effective
      method of draining SRF in rhegmatogenous retinal detachments.

PMID- 9524029
TI  - Primary choroidal malignant melanoma occurring in a New Zealand Maori.
AB  - PURPOSE/METHOD: A case of a 28-year-old Maori with an aggressive primary
      choroidal malignant melanoma is presented. RESULTS/CONCLUSION: Melanoma and
      particularly intra-ocular melanoma is very rare in pigmented races. This is the
      first reported case in the Maori.

PMID- 9524030
TI  - Ocular anomalies in the branchio-oculo-facial syndrome.
AB  - PURPOSE: To describe the ocular anomalies in two cases of branchio-oculo-facial
      syndrome (BOFS). METHODS: Two cases of BOFS are reviewed. RESULTS/CONCLUSIONS:
      Branchio-oculo-facial syndrome is a rare branchial cleft syndrome that is
      characterized by a typical facial appearance of pseudo-cleft or cleft lip,
      subauricular branchial sinuses, deafness and ocular anomalies, which include
      nasolacrimal obstruction, telecanthus and colobomata. It has an autosomal
      dominant inheritance pattern.

PMID- 9524031
TI  - Corneal scarring and irregular astigmatism following refractive surgery in a
      corneal transplant.
AB  - BACKGROUND: Scarring may follow refractive surgery, causing irregular astigmatism
      and loss of visual acuity. METHODS: A case report of scarring and irregular
      astigmatism occurring in a corneal transplant following photorefractive
      keratectomy and arcuate incisions is presented. RESULTS: Following surgical
      excision of the scar, unaided visual acuity improved from 1/60 to 6/12.
      Histopathology of the excised scar was obtained. CONCLUSIONS: Refractive surgery
      following corneal transplantation may produce scarring. The origin of the scar in
      the present case has not been established.

PMID- 9524032
TI  - Recurrent scleritis in lepromatous leprosy.
AB  - BACKGROUND: Recurrent immune-mediated scleritis after adequate treatment of
      leprosy is not well documented in the literature. We describe an Australian
      resident with unilateral intra-ocular lepromatous leprosy who had persistent non
      infectious scleritis. METHODS: A man of Anglo-Indian ancestry initially presented
      with lepromatous leprosy and unilateral ocular involvement. The affected eye had
      an interstitial keratitis and a granulomatous anterior uveitis that responded to
      antileprotics and anti-inflammatory agents. Despite systemic cure with triple
      antileprotic therapy, he developed recurrent scleritis that required multiple
      scleral patch grafts for scleral thinning and, subsequently, an enucleation.
      Histology failed to demonstrate persistent infection, rather a chronic non
      granulomatous scleritis, which was probably immune mediated. RESULTS/CONCLUSIONS:
      This case demonstrates an ocular complication of leprosy that is infrequently
      reported. Patients with ocular involvement by leprosy are at risk of developing
      recurrent scleritis despite systemic cure with antileprotics.

PMID- 9524033
TI  - Subretinal perfluorodecalin toxicity.
AB  - BACKGROUND: Subretinal injection of perfluorocarbon liquids (PFCL) can occur
      during vitreoretinal surgery. The long-term effects of this complication are not
      well established. METHODS: A case report is presented of a patient with retained
      subretinal perfluorodecalin following retinal detachment repair for a giant
      retinal tear. RESULTS: In the early postoperative period, the macular retinal
      pigment epithelium (RPE) became opalescent in appearance and by 2 months
      postoperatively the patient developed macular RPE atrophy with resulting poor
      central vision. CONCLUSIONS: Toxicity of subretinal perfluorodecalin causing RPE
      atrophy is proposed. We recommend all traces of PFCL should be removed if
      possible.

PMID- 9524034
TI  - Perforating eye injuries from external rear vision mirrors.
AB  - PURPOSE: To highlight external rear vision mirrors as a cause of ocular injuries
      in motor vehicle accidents. METHODS: Three cases of perforating eye injuries due
      to shattered external rear vision mirrors in motor vehicle accidents are
      described. The relevant Australian design rules are reviewed. RESULTS/CONCLUSION:
      External rear vision mirrors can be responsible for serious ocular injuries in
      motor vehicle accidents. Further investigation of the incidence of such injuries
      is required to determine whether vehicle manufacturing methods and the design
      rules covering their production warrant revision.

PMID- 9524035
TI  - Visual hallucinations and macular degeneration: an example of the Charles Bonnet
      syndrome.
AB  - PURPOSE: Patients with any form of visual disturbance, no matter how unusual,
      often present first to their ophthalmologist. An example of the Charles Bonnet
      syndrome as a result of bilateral macular degeneration is presented. The
      significance of early diagnosis is highlighted as reassurance and explanation of
      the condition seems to be the cornerstone of management. METHODS/RESULTS: A
      chronological case history, results of investigations and management are
      presented. CONCLUSIONS: The diagnosis of Charles Bonnet syndrome should be
      considered in elderly, cognitively intact patients who present with vivid,
      elaborate and complex visual hallucinations following ocular pathology. Although
      there is no universal definition of this entity and there is no specific
      pharmacotherapy, patients may be referred for counselling.

PMID- 9524036
TI  - Pathogenesis of macular degeneration: is there any progress?

PMID- 9524037
TI  - Electrophysiology: a review of signal origins and applications to investigating
      glaucoma.
AB  - Because different electrophysiological responses can be isolated to different
      retinal and cortical cell types and levels, the proportion in which the different
      signals are reduced can reflect the primary areas of damage. The knowledge of
      electrophysiology component sources can thus be applied when examining ophthalmic
      disorders. The present review covers the proposed origins and the usefulness of
      the conventional electrophysiological responses. Their application to glaucoma is
      discussed, with particular reference to the pattern electroretinogram. In the
      second part of the current review, we present some recent developments that
      relate to the use of multifocal pseudorandomly stimulated recording. This
      technique enables a new approach to the electrical assessment of visual
      responses. Analysis for temporal non-linearities and spatial distribution of the
      response throughout the visual field can be implemented. This type of recording
      has the potential to provide a method of objective visual field assessment in
      glaucoma and other disorders of the visual system.

PMID- 9524038
TI  - Immunocytochemical localization of basic fibroblast growth factor and glial
      fibrillary acidic protein after laser photocoagulation in the Royal College of
      Surgeons rat.
AB  - PURPOSE: Argon laser photocoagulation slows photoreceptor degeneration in the
      Royal College of Surgeons (RCS) rat, as does intravitreal injection of basic
      fibroblast growth factor (bFGF). We hypothesize that up-regulation of retinal
      bFGF is a consequence of laser lesioning in RCS rats. Therefore, we examined the
      localization of bFGF after laser and correlated this with Mailer cell glial
      fibrillary acidic protein (GFAP) expression, which is known to increase after
      injury. METHODS: A total of 34 RCS rats at postnatal day 23 were anaesthetized
      (ketamine 40 mg/kg) and their retinas were irradiated with a grid pattern of 40
      non-overlapping argon green lesions with a power of 120 mW for 0.2 s using a 50
      microm spot size. At 0, 6, 12, 24 and 48 h and 7, 14 and 21 days post-lesion,
      rats were anaesthetized and their eyes were enucleated and cryostat sectioned and
      the sections were processed using either an antibody to bFGF or GFAP using the
      standard avidin-biotinylated peroxidase complex method. Five age-matched RCS rats
      without laser lesions served as controls. RESULTS: Basic fibroblast growth factor
      immunoreactivity (IR) was normally located within cells in the ganglion cell
      layer inner nuclear layer and in retinal pigment epithelium cells and in the
      extracellular matrix/cell membranes of the outer nuclear layer (ONL). In lasered
      retinas, there was elevated bFGF-IR in the coagulated outer segments for the
      first 24 h. Retinal blood vessels/Muller cells/astrocytes were moderately
      labelled in and near each lesion immediately after lesion and became more intense
      after 48 h and persisted for at least 21 days. There was an elevation of bFGF-IR
      in the ONL on the lesion flanks at 14 days. Muller cell GFAP-IR was first
      detected at 6 h post-lesion and spread for a considerable distance beyond the
      lesion site. At 7 and 14 days, Muller cells at the lesion site had sprouted,
      while those on the flanks were still GFAP-IR. CONCLUSIONS: Following laser lesion
      there was an increase in bFGF at the lesion core only for the first 24 h.
      However, elevated levels of bFGF were observed in the ONL at 14 days, which
      extended into the lesion flanks for a similar distance to that over which
      increased photoreceptor survival is found. These results provide support for the
      hypothesis that laser lesions induce bFGF and this may be the mechanism whereby
      photoreceptors are spared. Muller cell activation is consistent with growth
      factor stimulation, but was more widespread than the bFGF changes in ONL.
      However, blood vessel labelling was similarly widespread and so the responses may
      be linked between Muller cell GFAP reaction and blood vessel bFGF localization
      after laser lesions.

PMID- 9524039
TI  - Polyhexamethylene biguanide treatment for Acanthamoeba keratitis.

PMID- 9524040
TI  - Evolution of oculomotor muscles.

PMID- 9524041
TI  - Characterization of angiotensin-(1-7) in the urine of normal and essential
      hypertensive subjects.
AB  - A total of 31 healthy volunteers [39 +/- 7 (SD) years] and 18 untreated essential
      hypertensive subjects [43 +/- 9 years] collected urine for 24 h after a physical
      examination and laboratory tests. Radioimmunoassay measurements of angiotensin-(1
      7) [Ang-(1-7)] in urine and plasma were done as described previously. Sitting
      systolic and diastolic blood pressures (+/- SD) averaged 118 +/- 11/74 +/- 7 mm
      Hg and 146 +/- 16/96 +/- 8 mm Hg in normal and essential hypertensive subjects,
      respectively (P < .001), whereas 24 h urinary volume was not different in normal
      and essential hypertensive subjects (P > .05). The concentration of Ang-(1-7) in
      the urine of normal subjects averaged 62.6 +/- 22.6 pmol/L corresponding to a
      urinary excretion rate of 98.9 +/- 44.7 pmol/24 h. Concurrent measurements of
      plasma Ang-(1-7) showed that the content of Ang-(1-7) in urine was 2.5-fold
      higher than that measured in the plasma. In contrast, untreated essential
      hypertensive subjects had lower concentrations and 24 h urinary excretion rates
      of Ang-(1-7) averaging 39.4 +/- 18.0 pmol/L and 60.2 +/- 14.6 pmol/24 h,
      respectively, (P < .001). Differences in the excretory rate of Ang-(1-7) between
      normal volunteers and essential hypertensive subjects were not modified by
      normalization of the data by urinary creatinine excretion rates. Urinary
      concentrations of Ang-(1-7) correlated inversely with systolic, diastolic and
      mean arterial pressures (r = -0.48, P < .001). Both urinary Ang-(1-7) [odds ratio
      of 0.92 (95% CI: 0.88-0.97)] and age were independent predictors of systolic
      blood pressure. These studies demonstrated the presence of Ang-(1-7) in urine and
      the existence of reduced levels of the heptapeptide in individuals with untreated
      essential hypertension. The relatively higher concentrations of Ang-(1-7) in
      urine compared to plasma agrees with data that showed that Ang-(1-7) may
      contribute to the regulation of blood pressure. The inverse association between
      Ang-(1-7) and arterial pressure provides a potential marker for the
      characterization of forms of essential hypertension associated with reduced
      production or activity of vasodilator hormones.

PMID- 9524042
TI  - Structural abnormalities and not diastolic dysfunction are the earliest left
      ventricular changes in hypertension. HARVEST Study Group.
AB  - It has been claimed that diastolic dysfunction is the earliest cardiac
      abnormality in hypertension, preceding the development of left ventricular (LV)
      structural abnormalities. To detect early signs of hypertensive cardiac
      involvement 722 subjects (533 men and 189 women), 18-45 years old, with stage I
      hypertension, were studied by M-mode and Doppler echocardiography. Blood pressure
      was measured by 24-h ambulatory monitoring. Ninety-five normotensive individuals
      of similar age and gender distributions were studied as controls. Significant,
      though modest, changes of LV mass and geometry were found in the participants in
      comparison with the normotensive controls. The increment was +10.4 g/m2 for LV
      mass index, +1.8 mm for LV wall thickness, and +0.032 for relative wall
      thickness. A slight increase in atrial filling peak velocity was found in the
      hypertensive subjects at Doppler analysis of transmitral flow, but the ratio of
      early to atrial velocity of LV diastolic filling did not differ between the two
      groups. In multiple regression analyses, which included age, body mass index,
      heart rate, smoking, and physical activity, 24-h mean blood pressure emerged as a
      significant predictor of LV mass index (men, P = .003; women, P = .04) and wall
      thickness (men, P = .03; women, P = .004) in the hypertensive subjects, whereas
      no index of diastolic filling was significantly associated with ambulatory blood
      pressure in either gender. The present data indicate that changes in LV anatomy
      are the earliest signs of hypertensive cardiac involvement. Left ventricular
      filling is affected only marginally in the initial phase of hypertension.

PMID- 9524043
TI  - Ultrasonic myocardial texture in hypertensive mild-to-moderate left ventricular
      hypertrophy: a videodensitometric study.
AB  - Myocardial texture analysis of two-dimensional echocardiographic gray level
      distribution is abnormal in hypertensive patients with severe increase of left
      ventricular mass. The aim of this study was to investigate the behavior of this
      parameter in hypertensive patients with absent-to-moderate left ventricular
      hypertrophy, more representative of the overall hypertensive population. We
      compared male essential hypertensive patients, with absent or mild-to-moderate
      left ventricular hypertrophy, with normotensive sedentary healthy subjects as
      controls. The groups (n = 18 each) were age- (+/- 2 years) and sex-matched. All
      subjects performed ambulatory blood pressure measurements for the evaluation of
      24 h mean systolic and diastolic blood pressure. Quantitative analysis of
      echocardiographic digitized imaging was performed through a calibrated 256 gray
      level digitization system to calculate midseptum and midposterior end-diastolic
      and end-systolic first and second order textural analysis. In particular were
      observed the mean gray level cyclic variations to deriving the cyclic variation
      index (CVI). The hypertensives showed a significantly lower CVI compared with
      controls both for septum (P < .001) and for posterior wall (P < .0001). No
      significant relationships were found between CVI and relative diastolic thickness
      both of septum and posterior wall. Conversely, a significant inverse relationship
      was found between systolic arterial pressure values and CVI both of septum and
      posterior wall. Abnormalities of two dimensional echocardiographic gray level
      distribution are present also in hypertensive patients with absent or with mild
      to-moderate levels of left ventricular hypertrophy, but seem unrelated to the
      degree of echocardiographic hypertrophy as such. Changes in collagen network
      distribution or microcirculatory alterations, secondary to pressure-volume
      overload per se or to other complex humoral factors, could explain these
      abnormalities. Further work is needed to establish the clinical, therapeutic, and
      prognostic implications of these findings.

PMID- 9524045
TI  - Contribution of angiotensin I converting enzyme gene polymorphism and
      angiotensinogen gene polymorphism to blood pressure regulation in essential
      hypertension.
AB  - The renin-angiotensin system (RAS) is involved in the pathogenesis of essential
      hypertension. In the present study we examined the genotype frequencies of the
      insertion/deletion polymorphisms of the ACE gene and the M235T polymorphism of
      the Angiotensinogen (Agt) gene in patients with essential hypertension in
      comparison with normotensive subjects. In hypertensive patients functional
      effects of blood pressure response to ACE inhibition were investigated. A total
      of 121 patients with essential hypertension (group 1) and 125 normotensive
      control subjects (group 2) were included in this study. All patients were
      genotyped by polymerase chain reactions (PCR) for the insertion/deletion (I/D)
      polymorphism of the ACE gene and the M235T polymorphism of the Agt gene. To
      analyze possible functional impacts on blood pressure regulation 50 mg of
      captopril was administered to hypertensive patients. No significant association
      of essential hypertension with polymorphisms of the Agt and ACE gene was found.
      The ACE serum levels in patients with the DD-genotype of the ACE I/D polymorphism
      were higher than in patients with the II-genotype (P < .01). In patients with the
      ID-genotype the ACE serum levels were in-between. A captopril test was performed
      in hypertensive patients. The patients were further divided into subgroups
      according to the diastolic and systolic blood pressure response. Group 1a
      consisted of patients with a diastolic blood pressure drop of > 5 mm Hg and group
      1b with < or =5 mm Hg. Group 1c consisted of patients with a systolic blood
      pressure drop of > 10 mm Hg and group 1d with < or =10 mm Hg. Twice as many
      patients with the DD genotype of the ACE gene were found in group 1a compared to
      group 1b (chi(2) = 5.673; P = .017). No association of systolic blood pressure
      change to the investigated polymorphisms was found. Our results do not support
      the hypothesis that the investigated polymorphisms contribute to essential
      hypertension. Furthermore, no major impact of these polymorphisms on blood
      pressure response to captopril were detected. We conclude that the investigated
      genotypes have no influence on blood pressure level and homeostasis.

PMID- 9524044
TI  - Short-term effects of withdrawing angiotensin converting enzyme inhibitor therapy
      on home self-measured blood pressure in hypertensive patients.
AB  - The aim of this study was to compare blood pressure rise after interruption of
      two angiotensin converting enzyme (ACE) inhibitors in hypertensive patients.
      After a 2-week placebo run-in period, hypertensive patients were treated with
      either trandolapril 2 mg once daily or perindopril 4 mg once daily for 4 weeks in
      a double-blind design. A placebo was then administered for 1 week. Three periods
      of 1-week home self-measured blood pressure (SMBP) were programmed: end of
      placebo run-in period, end of treatment period, and final withdrawal placebo
      period. Every day, three consecutive measurements were requested both in the
      evening and in the morning. Individual reversion to baseline BP level was studied
      in the subgroup of patients responding to therapy (evening diastolic SMBP
      decrease > or =6 mm Hg). The ratio (R) of mean post-drug DBP lowering (residual
      effect) over evening on-drug DBP lowering (full effect) was used to study
      reversion to baseline. Patients exhibiting a lower value than the median of this
      ratio were called Reverters, whereas others were called Nonreverters. One hundred
      nineteen patients entered the analysis. During the treatment period, mean SMBP
      decreased significantly, from 150 +/- 14/97 +/- 7 mm Hg to 139 +/- 15/91 +/- 9 mm
      Hg (all P < .001). The on-drug BP level was similar in the evening in the two
      treatment groups. However, both systolic and diastolic morning SMBP levels were
      significantly lower in the trandolapril group. After drug discontinuation, the
      mean BP level significantly rose to 144 +/- 14/94 +/- 9 mm Hg (all P = .01) but
      remained lower than the baseline BP values (P = .003 for SBP and P = .002 for
      DBP). The post-drug BP level was significantly lower in the trandolapril group
      than in the perindopril group. Seventy-four patients were responders to therapy.
      In this subgroup, the median of the R ratio used to analyze reversion to baseline
      after drug discontinuation was 44%. Nonreverters were characterized by a
      sustained on-drug BP decrease, compared to Reverters. We therefore conclude that
      ACE inhibitor treatment withdrawal is accompanied by a rapid rise in BP (within
      48 h), followed by a 5-day BP plateau that is lower than the initial level.
      Reverters to baseline after drug discontinuation were more likely to be
      insufficiently controlled during therapy, particularly in the morning. The longer
      duration of action of trandolapril was associated with a lower BP level during
      both the morning during the active treatment phase and the 1-week posttreatment
      phase.

PMID- 9524047
TI  - Leg versus forearm flow: 24 h monitoring in 14 normotensive subjects and in 14
      age-matched hypertensive patients confined to bed.
AB  - A circadian blood pressure rhythm has been demonstrated in the majority of
      subjects, even if inactive during daytime. A rhythm of leg blood flow and
      peripheral resistance, with higher values during sleep than during waking, has
      also been recently shown in subjects confined to bed. Doubts still persist on
      whether such a rhythm also exists in the forearm, and whether or not its trend is
      similar to that found in the leg. In this study, leg and forearm blood flow and
      resistance were monitored noninvasively every 15 min for 22 h in 14 normotensives
      and 14 age-matched hypertensives confined to bed. A significant blood pressure
      fall (normotensives, -4.8%/-6.1%; hypertensives, -7.1%/-6.3%; all P <.0001),
      heart rate decrease (-14.9 in the former, -10% in the latter; both P <.0001) and
      leg flow increase (normotensives, +47.4%, hypertensives, +36.1%; both P <.0001)
      were found during sleep in all subjects, because of a blood redistribution
      probably attributable to activation of the cholinergic system. Forearm flow was
      significantly higher during sleep (+26.1%, P <.0001) in the normotensives,
      whereas in the hypertensives a slight nocturnal decrease (-1.9%) was found. In
      conclusion, the hypertensives had lower leg and forearm flow than the
      normotensives during sleep and similar during daytime. Peripheral resistance
      measured in the leg and in the forearm was greater in the former than in the
      latter, both during sleep and during waking.

PMID- 9524046
TI  - Hemodynamic and metabolic effects of transdermal clonidine in patients with
      hypertension and non-insulin-dependent diabetes mellitus.
AB  - The aim of this study was to evaluate the effect of transdermal clonidine on
      hemodynamic and metabolic parameters in patients who have elevated blood pressure
      and non-insulin-dependent diabetes mellitus (NIDDM). After a 2-week run in
      placebo period, 20 NIDDM patients who had diastolic blood pressure in the range
      of 90 to 105 mm Hg underwent a randomized, single blind, placebo controlled,
      cross-over study of 4 week treatment with clonidine (transdermal patch 2.5
      mg/week) or placebo (inactive patch). Compared with placebo, clonidine
      significantly reduced systolic (153 +/- 6 v 163 +/- 8) and diastolic (88 +/- 2 v
      98 +/- 3.5 mm Hg, P = .001) blood pressure, left ventricular mass (94 +/- 11 v 99
      +/- 12 g/m2, P < .01) and fasting glucose levels. Total glucose disposal (glucose
      clamp) was 6.5 +/- 1.5 with placebo and 7.1 +/- 1.6 mg/kg/min with clonidine (P <
      .01). Oxidative glucose disposal (indirect calorimetry) was also greater after
      clonidine. Plasma glucose, insulin, and C-peptide responses following oral
      glucose (75 g) were significantly lower after clonidine, as well as urinary
      albumin excretion. Transdermal clonidine is effective in reducing blood pressure
      in hypertensive NIDDM patients and is well tolerated. It may be useful to reduce
      the cardiovascular impact of hypertension in diabetes mellitus.

PMID- 9524048
TI  - Ethnic (black-white) contrasts in heart rate variability during cardiovascular
      reactivity testing in male adolescents with high and low blood pressure: the
      Bogalusa Heart Study.
AB  - Heart rate variability (HRV) is used to study autonomic effects on the heart. The
      time domain PNN50 (percentage of consecutive RR intervals differing by > 50%)
      measures high frequency in HRV primarily reflecting parasympathetic activity. The
      ratio of low to high frequency power (LF/HF) measured by fast Fourier analysis is
      used to measure sympathetic to parasympathetic balance. In adults, increased
      sympathetic tone has been found in hypertensive individuals. The present study
      was performed to look for differences in HRV by race and between subjects with
      high and low blood pressure (BP). Heart rate variability data was analyzed from
      Holter monitor recordings in 39 healthy male subjects aged 13 to 17 years (50%
      white). Half were selected with Korotkoff fourth sound (K4) DBP > 85th percentile
      for height measured twice, 3 to 5 years apart (average 116/75 mm Hg). Half had
      DBP < 15th percentile for height (average 101/57 mm Hg). Subjects underwent a
      physical examination including BP, height, and weight before cardiovascular
      reactivity testing including measurements taken while supine and standing, and
      during 20% maximal isometric hand grip, Valsalva maneuver, and immersion of the
      hand in water at 4 degrees C. The LF/HF ratio was significantly higher and the
      PNN50 was significantly lower in whites compared with ratios for blacks during
      all CV reactivity tests (all P < .05). There was a trend for higher LF/HF ratio
      and lower PNN50 in blacks and whites with higher levels of BP, although this did
      not reach statistical significance. It was concluded that healthy white
      adolescents exhibit increased sympathetic tone compared with that of blacks
      during CV reactivity tests. A trend towards sympathetic predominance during
      reactivity testing was demonstrated in children with higher levels of DBP.

PMID- 9524049
TI  - The effects of talking, reading, and silence on the "white coat" phenomenon in
      hypertensive patients.
AB  - To explore the mechanisms of the "white coat" phenomenon, the effects of talking,
      reading, and silence were analyzed. Fifty essential hypertensive patients were
      randomly allocated to periods of stress talking and relaxing reading, alternating
      with three periods of silence. While talking, systolic/diastolic blood pressure
      increased sharply, from 142 +/- 0.7/97.7 +/- 0.5 mm Hg to 159 +/- 0.7/111 +/- 0.5
      mm Hg (P < .0001). While reading, systolic/diastolic blood pressure decreased (P
      < .0001). Moreover, talking and reading had opposite residual effects. The
      silence and reading periods gave the best approximations of the daytime
      ambulatory period. The predictive value of clinical blood pressure can be
      improved if measured during a period without talking, thus decreasing the "white
      coat" phenomenon.

PMID- 9524050
TI  - Ambulatory blood pressure in air traffic controllers.
AB  - Conflicting reports exist as to whether air traffic controllers (ATC) have an
      increase in blood pressure (BP) and prevalence of hypertension because of the
      stressful nature of their job. We have addressed the issue in male ATC working at
      the Linate airport of Milan. A total of 80 ATC participated, and the 24 h blood
      pressure monitoring was obtained during two working shifts separated by one night
      of rest. Blood pressure was measured conventionally and by 24 h ambulatory
      monitoring; data were compared with those of an age matched male sample three
      times as large, selected from the data of the Studio delle Pressioni
      Ambulatoriali delle Loro Associazioni (PAMELA), ie, a large sample representative
      of the population of the nearby town of Monza. Treated hypertensive subjects were
      excluded from both groups. Conventional diastolic BP and heart rate were similar
      in ATC and controls, whereas conventional systolic BP was significantly greater
      in the former than in the latter group. No difference, however, was seen between
      ATC and controls as far as ambulatory BP and heart rate were concerned; namely,
      24 h, day, and night average systolic BP, and diastolic BP and heart rate were
      similar in the two groups. Thus daily life BP is not increased in ATC. This may
      result from the fact that, being a highly selected group with suitable training,
      these subjects adequately cope with the stress inherent to the job.

PMID- 9524051
TI  - Stored renin isoforms in the developing rat kidney.
AB  - Fetal rat kidney contains renin in renal microvasculature, whereas adult rat
      kidney contains renin predominantly in juxtaglomerular cells. It is hypothesized
      that renin isoforms stored within these renal tissues may differ chemically and
      functionally. To test this hypothesis, stored renin isoforms in fetal and adult
      rat kidney were compared by isolating renin from adult and fetal kidney
      homogenate with pepstatin agarose. Pepstatin-eluted renin isoforms were separated
      by relative molecular size using one-dimensional polyacrylamide gel
      electrophoresis (SDS-PAGE), or by isoelectric point (pI) and size using two
      dimensional (2D) gel electrophoresis. Isoforms were identified either by silver
      staining or immunoblotting. One-dimensional polyacrylamide gel electrophoresis of
      pepstatin-treated kidney homogenates showed a silver-stained band in the range of
      approximately 45 kDa, which corresponded to a silver-stained spot consistently
      seen on 2D gels. In fetal kidney homogenate, the approximately 45 kDa band had a
      pI of 5.3 +/- 0.1, whereas the corresponding band in adult samples had a basic pI
      of 6.0 +/- 0.05. Angiotensin I generation was measured to assess renin enzymatic
      activity. There was significantly more inactive renin in fetal kidney homogenate
      than in adult kidney homogenate (60.2 +/- 22.4 v 9.6 +/- 4.0 ng AI/mg protein/h,
      P < .05). There was significantly less active renin in fetal kidney homogenate
      than in adult kidney homogenate (5.4 +/- 0.4 v 36.5 +/- 14.2 ng AI/mg protein/h,
      P < .05). The average total renin activity in fetal kidney homogenate was
      significantly higher than in adult kidney homogenate (65.6 +/- 22.3 v 46.0 +/-
      15.2, P < .05). These results demonstrate major differences in the physical and
      enzymatic forms of stored renin found in fetal and adult kidney. It is speculated
      that these variations in stored renin isoforms play a role in the developmental
      differential regulation of the intrarenal renin angiotensin system.

PMID- 9524052
TI  - Impaired basal sympathetic tone and alpha1-adrenergic responsiveness in
      association with the hypotensive effect of melatonin in spontaneously
      hypertensive rats.
AB  - Early investigations have suggested a relationship between hypertension and
      melatonin, a pineal hormone. The aims of this study were to evaluate the
      implication of the sympathetic nervous system in the acute effect of melatonin on
      blood pressure in conscious 12-week-old spontaneously hypertensive rats (SHR) and
      Wistar-Kyoto rats (WKY), and to determine whether the hypotensive effect of
      melatonin is associated with alterations in pre- or postsynaptic mechanisms.
      Melatonin, 10 mg/kg, produced a sustained time-dependent decrease of mean
      arterial pressure only in SHR without changes in heart rate in both groups. Until
      20 min after melatonin administration, plasma epinephrine (EPI) levels were
      reduced by about 60% in both groups, but norepinephrine (NE) levels were
      decreased only in SHR by about 30%. The nitroprusside-induced hypotension
      responses and the associated increases in heart rate were similar in both groups
      before or after administration of melatonin. Unexpectedly, the sympathetic
      reactivity to nitroprusside, evaluated by the increases in NE and EPI, was
      markedly enhanced after melatonin treatment in both WKY and SHR. The stimulation
      induced [3H]-norepinephrine release from isolated atria was not altered by
      melatonin in SHR. In cultured aortic vascular smooth muscle cells, the basal and
      phenylephrine induced inositol phosphate formations were greater in SHR, and the
      melatonin pretreatment dose dependently attenuated the phenylephrine responses in
      cells from both WKY and SHR. Therefore the hypotensive action of melatonin
      appears to be associated with an inhibition of basal sympathoadrenal tone and
      could also be mediated partly by the blockade of postsynaptic alpha1-adrenergic
      receptor-induced inositol phosphate formation.

PMID- 9524053
TI  - The effects of alcohol consumption on ambulatory blood pressure and target organs
      in subjects with borderline to mild hypertension. HARVEST Study Group.
AB  - The objective of this study was to examine the relationship of alcohol
      consumption to target organ involvement and ambulatory blood pressure (BP) in a
      population of young borderline to mild hypertensive subjects. Participants were
      793 male subjects, aged 18-45 years, from the HARVEST Study. The analysis was
      performed in three age-matched groups with similar body mass index. Casual and 24
      h ambulatory BP monitoring, routine biochemistry, echocardiography, and albumin
      excretion rate were measured. The men were divided into three groups: 1)
      nondrinkers, 2) drinkers of < 50 g/day, and 3) drinkers of > or = 50 g/day.
      Office systolic BP was not significantly different among the three groups,
      whereas 24-h and daytime BPs increased progressively from the first to the third
      group (group 1 v 3; P = .01 for 24-h systolic BP and P = .02 for daytime systolic
      BP). These differences remained significant even after adjusting for smoking.
      Left ventricular mass index, interventricular septum thickness, and wall
      thickness increased progressively from group 1 to group 3; this difference also
      remained significant after adjusting for smoking and 24-h BPs. The albumin
      excretion rate was much higher in group 3 than in group 1 (P = .003), but when 24
      h BP was added to the model the difference was no longer significant. These
      results indicate that alcohol has a detrimental effect on the heart and the
      kidney. Alcohol's effect on LV wall thickness appears to be direct, whereas its
      action on albumin excretion rate seems to be mediated mainly by its effect on BP.

PMID- 9524054
TI  - Plasminogen activator inhibitor-1 and angiotensin I converting enzyme gene
      polymorphism in patients with hypertension.
AB  - Deletion polymorphism of angiotensin I-converting enzyme (ACE) gene has been
      reported to be an independent risk factor for myocardial infarction. Plasminogen
      activator inhibitor-1 (PAI-1) was proposed to be a link between the renin
      angiotensin system and thrombotic risk. This study was undertaken to investigate
      the possible association between the insertion/deletion (I/D) polymorphism of the
      ACE gene and plasma PAI-1 levels in 160 patients with mild-to-moderate
      hypertension. The I/D genotypes were determined by polymerase chain reaction with
      oligonucleotide primers flanking the polymorphic region in intron 16 of the ACE
      gene. Baseline levels of PAI-1 antigen and activity and tissue plasminogen
      activator (t-PA) antigen were determined in fasting morning plasma samples. It
      was found that patients with homozygote deletion (DD, n = 37) ACE genotype did
      not have significantly higher plasma levels of PAI-1 antigen (31.2 +/- 15.6 ng/mL
      v 28.4 +/- 15.1 ng/mL or 27.2 +/- 13.2 ng/mL, P = .42), PAI-1 activity (16.2 +/-
      10.6 IU/mL v 14.1 +/- 9.4 IU/ mL or 15.0 +/- 9.9 IU/mL, P = .60), or t-PA antigen
      (14.6 +/- 6.0 ng/mL v 13.4 +/- 4.9 ng/mL or 14.6 +/- 5.7 ng/mL, P = .40) as
      compared to those with heterozygote (DI, n = 67) or homozygote insertion (II, n =
      56) genotypes. On multiple regression analysis, the ACE genotypes did not appear
      to be significant predictors for plasma PAI-1 levels and t-PA antigen after
      adjustment with age, sex, body mass index, plasma triglyceride, cholesterol, and
      glucose. In conclusion, the results indicated that the I/D polymorphism of the
      ACE gene was not related to plasma PAI-1 levels in a Chinese population with
      hypertension. The ACE genotypes may not have a role in influencing the
      fibrinolysis in hypertension.

PMID- 9524055
TI  - Stimulation of endothelial cell production of vasoconstrictive substances by
      hypertensive sera.
AB  - The endothelial cell regulates vessel tone by elaborating a number of vasoactive
      substances such as thromboxane and endothelin, both of which are highly
      vaosconstrictive, and prostacyclin and nitric oxide, both of which are
      vasodilatory. The current study examines the postulate that one of the mechanisms
      responsible for the increased vessel tone found in hypertension is the presence
      of substances in the sera of patients with this disorder that stimulates
      selectively the endothelial cell production of thromboxane and endothelin. Sera
      from ten patients with mild hypertension and from 11 age-matched controls were
      incubated with human umbilical arterial endothelial cells and the concentrations
      of endothelin, thromboxane, prostacyclin, and nitric oxide produced by the cells
      was measured in the supernatant. The results of the assays showed that the
      amounts of thromboxane and endothelin produced by endothelial cells in response
      to stimulation by hypertensive sera were significantly higher than the amounts
      produced in response to control sera; in comparison, the amounts of prostacyclin
      and nitric oxide produced by the cells in response to either hypertensive sera or
      control sera were not significantly different. The findings suggest that a
      mechanism that may be responsible for the increased vascular tone found in
      hypertension is the presence of substances in hypertensive sera that stimulate
      endothelial cells selectively to produce increased amounts of the
      vasoconstrictive hormones, endothelin and thromboxane.

PMID- 9524056
TI  - Blood pressure morning surge and hostility.
AB  - This study examined the effects of hostility on blood pressure (BP) during the
      early morning hours before awakening and several hours afterward. Our objective
      was to determine whether the pattern of BP change and the slope of the morning BP
      surge were related to hostility. The subjects were 32 patients with a history of
      Stage 1 hypertension. The morning surge in BP was derived from ambulatory BP
      monitoring of sleeping and waking hours, which were averaged per subject and
      centered around the wake-up hour. The periods used were 3 h before and 3 h after
      awakening. Only systolic blood pressure (SBP) is being reported on in this paper
      as this is the primary measure found relevant to the morning surge phenomenon.
      Hostility was assessed by the Buss-Durkee Hostility Inventory (total score). The
      results revealed significant differences between low and high hostility subjects
      for overall levels of sleep SBP: 120 +/- 11.4 mm Hg for low hostility and 131.3
      +/- 14.9 mm Hg for high hostility subjects (P = .02). Low hostility subjects
      showed a steep rise in SBP from sleeping to waking while high hostility subjects
      had almost reached their post-sleep level of SBP in the hours immediately before
      waking up (P = .03). These data indicate that individual differences in hostility
      are related to different patterns of BP during sleep and the early morning hours,
      a period of the day that has been associated with an increased risk of
      cardiovascular incidents. The data also suggest the need for further study of the
      significance of hostility and other personality traits and the relationship of
      these traits to the mechanisms of the morning surge and the risk of
      cardiovascular events.

PMID- 9524057
TI  - Genetic initiation of hypertensive and diabetic nephropathy.
AB  - The factors initiating the common etiologies of chronic renal failure remain
      elusive. This article reviews the evidence in support of a generalized genetic
      susceptibility to human end-stage renal disease, including kidney failure
      attributed to the systemic diseases of hypertension, diabetes mellitus, and
      glomerulonephritis. Molecular genetic techniques are powerful tools, assisting in
      the detection of the initiating factors in many complex diseases. In kidney
      disease, genetic methodologies complement the available anatomic, epidemiologic,
      and physiologic analyses. This article provides strategies to allow for the
      detection of human renal failure susceptibility genes. The identification of
      human renal failure genes would provide useful markers for disease susceptibility
      and speed the development of novel therapeutic strategies.

PMID- 9524058
TI  - Localization of a presumed catecholamine-secreting glomus tumor by 123I
      metaiodobenzyl guanidine (MIBG) single photon emission computed tomography
      (SPECT) scanning.
AB  - We present an unusual case of a 41-year-old woman with a known glomus tumor, an
      adrenal mass, hypertension, and elevated catecholamines. The glomus tumor was
      shown to be the site of excessive catecholamine production in what we believe to
      be one of the few descriptions of 123I-metaiodobenzylguanidine (MIBG) scanning
      for this uncommon tumor. The diagnostic difficulties of such a case are
      discussed. A literature review of catecholamine-secreting glomus tumors and a
      systematic approach to catecholamine-secreting tumor localization in such
      patients is presented. Therapeutic options of surgery, radiation therapy, and
      embolization are reviewed. We conclude that the management of patients with
      functioning glomus tumors needs to be individualized. A careful, systematic
      approach is required if needless surgery is to be avoided. Further, the use of
      123I-MIBG scanning deserves consideration to help localize catecholamine
      production in such patients.

PMID- 9524059
TI  - Vito Turk--a proactive catalyst not only in the field of cysteine proteinases and
      their inhibitors.

PMID- 9524060
TI  - An active zymogen: unravelling the mystery of tissue-type plasminogen activator.
AB  - In contrast to almost all other proteinases, human tissue-type plasminogen
      activator (tPA) is also proteolytically active in its zymogen or single-chain
      form. The closely related plasminogen activator isolated from vampire bat saliva
      (vPA) acts exclusively in the single-chain form, lacking the requisite cleavage
      site for proteolytic activation. Recent structural studies on the proteolytic
      domains of vPA and human tPA in two- and single-chain forms reveal the mechanism
      of this anomalous activity. The PA-catalyzed proteolytic conversion of
      plasminogen to plasmin, responsible for the initiation of fibrinolysis, is fibrin
      dependent; comparative structural analysis of the plasminogen activators provides
      clues as to the role of fibrin as cofactor.

PMID- 9524061
TI  - Thyropins--new structurally related proteinase inhibitors.
AB  - Thyroglobulin type-1 domain is a structural element found in a variety of
      functionally unrelated proteins. It may occur singly, as in insulin-like growth
      factor binding proteins, or multiply up to eleven, as in thyroglobulin. Some of
      these type-1 domain containing proteins have been shown to have the ability to
      inhibit either cysteine or cation-dependent proteinases. For these inhibitory
      proteins we proposed the term thyropins. These inhibitors originate from a
      variety of organisms and presumably have different biological functions. One of
      those whose function has been studied is the p41 invariant chain fragment. In
      vivo it associates with the major histocompatibility complex (MHC) class II
      molecule. The evidence supporting its involvement as a controlling factor in the
      process of antigen presentation is described.

PMID- 9524062
TI  - Cathepsin B and human tumor progression.
AB  - Cathepsin B has been implicated in progression of various human tumors.
      Overexpression of cathepsin B mRNA, increased cathepsin B staining and elevated
      cathepsin B activity have been found in different human cancers. These occur
      especially at the invasive edges of cancers, suggesting a role for cathepsin B in
      tumor invasion. In some tumors, mRNA expression and protein staining for
      cathepsin B correlate with clinical progression. Cathepsin B can facilitate tumor
      progression directly through degradation of components of the basement membrane
      and extracellular matrix. In vitro studies show that cathepsin B may exert its
      degradative effects intracellularly or extracellularly, depending on the cell
      type and location of cathepsin B. Cathepsin B can also facilitate tumor
      progression indirectly through activation of other latent proteases and/or
      degradation of protein inhibitors of other proteases. Thus cathepsin B may be an
      integral component of the proteolytic cascade linked to malignant progression of
      human tumors.

PMID- 9524063
TI  - Cysteine proteinases in cancer progression and their clinical relevance for
      prognosis.
AB  - Lysosomal cysteine proteinases, also known as cysteine cathepsins (Cats), belong
      to the papain family of proteinases, and share a similar protein structure and
      mechanism of action. However, subtle structural differences between these
      cathepsins, e.g. Cats B, H and L, give rise to potentially important variations
      in substrate specificity and differences in inhibition by their endogenous
      inhibitors, the cystatins, stefins and kininogens, under physiological and
      pathological conditions. Alterations in expression of Cat B and Cat L have been
      observed at various levels in malignant human tumor tissue compared to normal and
      benign tissue counterparts. We proposed that an imbalance between cathepsins and
      cystatins, associated with the metastatic tumor cell phenotype, may facilitate
      tumor cell invasion and metastasis and be responsible for early relapse of the
      disease after removal of the primary tumor. The results of our initial
      investigations on cysteine cathepsins and their endogenous inhibitors in human
      breast, lung and head and neck carcinomas, as well as in body fluids of melanoma
      and colorectal carcinoma bearing patients, have indeed shown their high
      prognostic impact for the survival of these patients.

PMID- 9524064
TI  - Gene regulation and extracellular functions of procathepsin L.
AB  - Cathepsin L, a lysosomal cysteine proteinase, belongs to the papain family. This
      proteinase is different from the other members of the mammalian papain family
      cysteine proteinase in the following ways: (i) The cathepsin L gene is activated
      by a variety of growth factors and activated oncogenes. (ii) Procathepsin L, a
      precursor form of cathepsin L is secreted from various cells. (iii) The mRNA
      level of cathepsin L is related to the in vivo metastatic potential of the
      transformed cells. Thus, the regulation of the cathepsin L gene and the
      extracellular functions of secreted procathepsin L are tightly coupled. In this
      review, we describe these two points, which have recently been addressed in our
      laboratory.

PMID- 9524065
TI  - Revised definition of substrate binding sites of papain-like cysteine proteases.
AB  - A review of kinetic and structural data has enabled us to reconsider the
      definition of substrate binding sites in papain-like cysteine proteases. Only
      three substrate binding sites, S2, S1 and S1', involve main as well as side chain
      contacts between substrate and enzyme residues. Interactions between the enzymes
      and the substrate P3 and P2' residues are based on side chains (an exception is
      cathepsin B which is a carboxydipeptidase), so their interaction surface spreads
      over a relatively wide area. The location and definition of substrate binding
      sites beyond S3 and S2' is even more questionable.

PMID- 9524066
TI  - Comparative analysis of the sequences and three-dimensional models of human
      procarboxypeptidases A1, A2 and B.
AB  - A full-length cDNA clone for preprocarboxypeptidase B from human pancreas has
      been isolated and sequenced. The open reading frame is 1254 bp in length,
      encoding a protein of 417 amino acids that includes a leader signal peptide of 15
      amino acids and a 95-amino acid-long pro-segment. It contains two differences
      when compared to the sequence reported for pancreas-specific protein, a human
      serum marker for acute pancreatitis identified as procarboxypeptidase B. The main
      difference is a previously unreported Cys at position 138, which is needed for
      the formation of one of the three disulphide bridges. Sequence alignments between
      human procarboxypeptidases A1, A2 and B and other known forms show that the most
      conserved region is the enzyme moiety followed by the globular domain of the pro
      segment. The maximum variability is found in the connecting region between
      moieties. The known three-dimensional structures of procarboxypeptidases from
      bovine and porcine species have been used to model all three human
      procarboxypeptidases and also to estimatethe interaction energies between the
      different parts of the molecules, in an attempt to gain insight into the
      structural features responsible for the differences observed in the functionality
      of the proenzymes, particularly in their proteolytic activation pathways. Taken
      together, the results obtained confirm that the main determinant for the rate and
      mode of activation of procarboxypeptidases is the strength of the interaction
      between the enzyme and the globular domain of the pro-segment, the connecting
      segment playing a complementary role.

PMID- 9524067
TI  - Immunological and functional analyses of the extracellular domain of human tissue
      factor.
AB  - Tissue factor (TF) initiates the extrinsic pathway of blood coagulation via
      formation of an enzymatic complex with coagulation factor VII/VIIa (FVII/VIIa).
      Although FVII is the only known ligand for TF, several reports in recent years
      have shown that the function of TF may not be limited to serving as a trigger of
      coagulation but that TF could also play a role in cellular signaling, metastasis,
      adhesion and embryogenesis. To explore the loci of the extracellular domain of TF
      important for its function, we analyzed the functional and immunological epitopes
      of TF1-219 by the use of both E. coli expressed TF variants encompassing various
      portions of the extracellular domain of TF and different anti-TF monoclonal
      antibodies (mAbs). N- and C-terminally truncated TF variants were analyzed for
      their VIIa-dependent procoagulant activity (PCA). The results obtained are in
      agreement with previously performed mutant and structural analyses of the
      interaction of FVII/FVIIa with the extracellular domain of TF. In addition, we
      observed that combination of two TF variants, Ec-TF1-122 and Ec-TF120-219, yields
      a soluble and active two-chain TF molecule with remarkable PCA. The reaction
      patterns of anti-TF mAbs with truncated TF variants and synthetic TF-derived
      peptides demonstrated that at least three distinct conformation-dependent epitope
      areas of TF (residues 1-25, 175-202, and 181 -214, respectively) are detected by
      these mAbs raised against native TF. In fact, mAbs, which are directed to the
      same epitope area of TF, behave very similar in various applications including
      immunohistochemistry and clotting tests. Since mAbs directed to the C-terminal
      epitope area of TF (residues 181-214) influence TF activity independent of FVIIa
      binding, this region may be involved in functions of TF distinct from
      haemostasis.

PMID- 9524068
TI  - Recombinant expression of human mast cell proteases chymase and tryptase.
AB  - Expression of recombinant human chymase and tryptase was achieved in a
      baculovirus-insect cell system using a fusion protein construct. Recombinant
      baculovirus was produced with DNA coding for a NH2-ubiquitin-chymase-COOH or NH2
      ubiquitin-tryptase-COOH fusion protein inserted immediately downstream of the
      signal sequence for the secreted envelope protein, glycoprotein 67. In each
      construct, the natural prepropeptide sequence of the protease was replaced by the
      amino acid sequence for the enterokinase cleavage site of trypsinogen. High Five
      insect cells infected with either of the modified baculovirus produced mg
      quantities of each fusion protein per liter of culture. Treatment of the chymase
      fusion protein with enterokinase or the tryptase-fusion protein with enterokinase
      in the presence of a highly charged polysaccharide (dextran sulfate or heparin)
      produced enzymatically active proteases with properties of the native enzymes. A
      procedure for the purification of mg quantities of recombinant chymase from
      infected-cell medium is presented.

PMID- 9524069
TI  - Molecular cloning and characterization of a novel tissue-specific calpain
      predominantly expressed in the digestive tract.
AB  - In the course of the genomic cloning of nCL-2, a stomach-specific calpain, we
      identified a genomic clone encoding a novel member of the calpain large subunit
      family and designated it 'nCL-4'. First, using exon sequences, we cloned the cDNA
      for mouse nCL-4. Based on this sequence, we also cloned the cDNAs for rat and
      human nCL-4. In the case of human nCL-4, the longest open reading frame encodes
      690 amino acid residues (Mr 79095) with equal sequence similarities (50-55%) to
      both ubiquitous and organ-specific calpain large subunits from mammals. The
      deduced amino acid sequence revealed that nCL-4 is highly conserved among
      mammals. nCL-4 can be aligned without significant deletions or insertions, and,
      thus, like other calpains, can be divided into four domains (I-IV). The
      significant similarity of domains II and IV to those in conventional calpain
      large subunits suggests the potential protease activity and Ca2+-binding ability
      of nCL-4. Northern blot analysis revealed that the mRNA for nCL-4 is expressed
      predominantly in stomach and small intestine but not in uterus, suggesting
      specialized functions of nCL-4 in the digestive tract. When overexpressed in COS
      7 cells, a specific band for nCL-4 was detected. In addition, the gene coding for
      nCL-4 was localized on human chromosome 1.

PMID- 9524070
TI  - Expression of human pro-matrix metalloproteinase 3 that lacks the N-terminal 34
      residues in Escherichia coli: autoactivation and interaction with tissue
      inhibitor of metalloproteinase 1 (TIMP-1).
AB  - Human pro-matrix metalloproteinase 3 (proMMP-3) lacking the N-terminal 34 amino
      acids and the C-terminal hemopexin-like domain was expressed in E. coli and used
      to investigate the process of proenzyme activation and its interaction with an
      endogenous inhibitor TIMP-1 during activation. The truncated precursor was
      purified from the E. coli extract in the presence of 5mM EGTA. The active 23.5
      kDa form was generated simply by exposure to Ca2+ and Zn2+ but not either by Ca2+
      alone or by Zn2+ alone. The rate of MMP-3(deltaC) formation was concentration
      dependent, indicating that autoactivation is a bimolecular reaction. The
      truncated precursor was able to interact with the N-terminal domain of TIMP-1
      without losing the 48 residue-long propeptide. However, upon a longer incubation,
      the propeptide was slowly processed, indicating that the association of the N
      terminally truncated proMMP-3 with TIMP-1 is weaker than that of the fully
      activated MMP-3 and TIMP-1. These results indicate that the expression of MMP
      activities is regulated by endogenous inhibitor TIMPs during their activation
      processes which provide an additional control mechanism of extracellular matrix
      breakdown.

PMID- 9524071
TI  - Human matrix metalloprotease activation by insults of bacterial infection
      involving proteases and free radicals.
AB  - We found that human matrix metalloproteases (MMPs) may be processed from their
      proenzyme forms (proMMP) to their active forms by two new and unique mechanisms:
      Firstly, by bacterial proteases such as Pseudomonas elastase and Vibrio cholerae
      protease, which cleave off the N-terminal autoinhibitory domain (so-called
      cysteine switch) from proMMPs. The second mechanism depends on free radical
      generation by activated polymorphonuclear leukocytes (PMNs). In this case,
      peroxynitrite (ONOO-) or nitrogen dioxide radical (.NO2), the reaction products
      of either superoxide (O2.-) or molecular oxygen (O2) and nitric oxide (.NO), are
      the key reactants. Both O2.- and .NO are generated by activated macrophages and
      PMNs as a result of immunologic responses involving various proinflammatory
      cytokines. .NO2 or ONOO- seems to interact with a single cysteine residue in the
      propeptide autoinhibitory domain, or so-called cysteine switch of proMMPs, thus
      transforming proMMPs into their active conformation. Furthermore, reactive oxygen
      species are known to inactivate the alpha1-protease inhibitor (alpha1-PI), a
      potent neutrophil elastase inhibitor in plasma. In addition, we found that such
      radicals activate MMPs which degrade and inactivate alpha1-PI by proteolysis.
      Thus, the activation of MMPs, accompanied by the inactivation of alpha1-PI, will
      bring about enhanced proteolytic damage to the matrix tissues of the infected
      sites by both MMPs and elastase.

PMID- 9524072
TI  - Comparison of calpains from rabbit, monkey, human and rat.
AB  - Two isozymes of calpain, mu-calpain and m-calpain, were purified from rabbit,
      monkey, human and rat tissues to homogeneity and the apparent molecular masses of
      the large and small subunits of each calpain species were compared directly.
      While the molecular masses of the small subunits were the same (28 kDa), those of
      the large subunits were different depending on the calpain type and animal
      species: Rabbit mu (79 kDa), rabbit m (75 kDa), monkey mu (79 kDa), monkey m (74
      kDa), human mu (78 kDa), human m (73 kDa), rat mu (75 kDa), and rat m (74 kDa).
      Ca2+-sensitivity of monkey mu-calpain was lower than that of rabbit mu-calpain,
      but m-calpains from rabbit and monkey shared a similar Ca2+-dependency.
      Immunoreactivities of rabbit, monkey and rat m-calpains towards anti-rabbit m
      calpain monoclonal antibodies were different depending on the antibody species,
      showing the existence of common and different antigenic sites in these three m
      calpains. While monkey mu-calpain still showed weak cross-reactivity with anti
      rabbit mu-calpain monoclonal antibodies, rat mu-calpain failed to react with any
      antibody examined, except for the monoclonal 1D10A7 which reacted with mu- and m
      calpains from any animal species. Peptides generated by V8 protease digestion
      were similar between mu-calpains or m-calpains from rabbit and monkey but, again,
      the reactivity of monkey calpain peptidesto anti-rabbit calpain antibodies was
      weak, especially to those of mu-calpain.

PMID- 9524073
TI  - Genetic variation of Porphyromonas gingivalis genes encoding gingipains, cysteine
      proteinases with arginine or lysine specificity.
AB  - Porphyromonas gingivalis hemagglutinating cysteine proteinases (gingipains) are
      considered as important virulence factors in the development of adult
      periodontitis. Using Southern blot analysis it was determined that genes of three
      distinct but related gingipains (gingipain-R1, gingipain-R2 and gingipain-K) were
      present in all tested strains including HG66, ATCC 33277, W50, E-20-1, EM-3, 381,
      A7436, and IKG5, with a region encoding a part of the hemagglutinin domain of
      gingipain-R1 and gingipain-K showing considerable variability. In contrast, the
      loci encoding gingipain-R1 (rgp1) and gingipain-R2 (rgp2) were strongly conserved
      excluding the concurrent occurrence of other gingipain-R-like genes such as cpgR
      and agp. Significantly, no evidence could be found to support the expression of a
      gene coding for the putative proteinase porphypain, an enzyme suggested to have
      both gingipain-R and gingipain-K activity.

PMID- 9524074
TI  - Changes in alpha-1-antichymotrypsin expression in vaccinia virus infected HepG2
      cells.
AB  - Human hepatoma cells (HepG2) synthesize and secrete several plasma proteins that
      are inhibited in a time- and dose-dependent manner after vaccinia virus
      infection. However, infection of the HepG2 cells with a low dose of the virus (up
      to 1 plaque forming unit/cell) stimulated the expression of alpha-1
      antichymotrypsin, which was demonstrated by means of electroimmunoassay and
      Northern blot analysis. This stimulation appeared to be on the level of
      transcription as shown in transient transfection experiments using various alpha
      1-antichymotrypsin gene promoter constructs. In contrast to interleukin-6, virus
      induced activation of the alpha-1-antichymotrypsin gene transcription does not
      require the STAT (signal transducers and activators of transcription) binding
      elements present in the alpha-1-antichymotrypsin gene promoter. Furthermore,
      alpha-amanitin, which inhibits eukaryotic RNA polymerase II and III, did not
      affect alpha-1-antichymotrypsin stimulation by the virus, indicating involvement
      of the viral transcriptional apparatus in transient activation of alpha-1
      antichymotrypsin gene expression.

PMID- 9524075
TI  - Sorting of non-glycosylated human procathepsin S in mammalian cells.
AB  - Cathepsin S, a lysosomal cysteine protease, is synthesized as inactive precursor.
      It is activated in the lysosomes by a proteolytic cleavage of the propeptide. HEK
      293-cells which do not express cathepsin S were transfected with cDNA of either
      wild type human procathepsin S or a mutant procathepsin S in which Asn of the
      only glycosylation site in the proregion was replaced by Gln. The cells expressed
      glycosylated and non-glycosylated procathepsin S, respectively. Large amounts of
      the precursors were secreted into the culture media by both transfectants.
      Secreted wild type procathepsin S contained Man-6-phosphate in the
      oligosaccharide chain. Wild type procathepsin S was activated in the cells but no
      maturation occurred in the culture media. In vitro processing of glycosylated as
      well as of non-glycosylated procathepsin S gave fully active enzymes thus
      indicating that the oligosaccharide chain was not necessary for proper folding. A
      reuptake of the glycosylated and non-glycosylated procathepsin S by HEK 293-cells
      could be observed. Small amounts of mature cathepsin S were detected in the
      lysosomes of the mutant transfectants. Subcellular fractionation showed non
      glycosylated procathepsin S in the membrane fraction. Non-glycosylated
      procathepsin S was bound to the plasma membrane at 2 degrees C, suggesting an
      additional sorting motif in the cathepsin S molecule besides the Man-6-phosphate
      residue.

PMID- 9524076
TI  - A hirudin-sensitive, growth-related proteinase from human fibroblasts.
AB  - We have identified a hirudin-sensitive proteinase from human fibroblasts.
      Inhibition of this enzyme results in partial inhibition of cell growth in
      culture. The enzyme has a molecular weight of about 38000, and can be isolated by
      affinity chromatography with a hirudin-agarose matrix. The enzyme is apparently
      not closely related to thrombin, but does show a high level of amino acid
      sequence homology with fragments of a protein isolated from the synovial fluid of
      rheumatoid arthritis patients, which acts as a mitogen for human T lymphocytes.

PMID- 9524077
TI  - Anticonvulsant drugs fail to modulate chemotherapy-induced cytotoxicity and
      growth inhibition of human malignant glioma cells.
AB  - Adjuvant chemotherapy after cytoreductive surgery and irradiation plays an
      increasingly important role in the management of human malignant glioma. Here we
      have examined the effect of three anticonvulsants most commonly administered to
      glioma patients, carbamazepine, phenytoin and valproic acid, on the cytotoxic and
      antiproliferative actions in vitro of several cancer chemotherapy drugs currently
      evaluated for human gliomas. We find that none of the anticonvulsants reduces
      glioma cell viability or proliferation or modulates glioma cell clonogenicity at
      clinically relevant concentrations when administered alone. Therapeutic
      concentrations of either drug fail to alter the effect of cancer chemotherapy
      drugs in acute cytotoxicity assays or modified clonogenicity assays. A lack of
      interactions of anticonvulsants and cytotoxic drugs is also observed when the
      glioma cells are preexposed to the anticonvulsants for prolonged times,
      suggesting that chronic exposure to anticonvulsants in vivo may not change
      intrinsic glioma cell sensitivity to cancer chemotherapy. Thus, changes in
      hepatic enzyme activity or immunological parameters, but not modulation of
      intrinsic chemotherapeutic drug sensitivity, may influence the choice of an
      anticonvulsant for seizure control in glioma patients receiving adjuvant
      chemotherapy.

PMID- 9524078
TI  - Cerebrovascular effects of the bradykinin analog RMP-7 in normal and irradiated
      dog brain.
AB  - The effects of an intravenous (i.v.) injection of the bradykinin analog RMP-7
      (100 ng/kg) were assessed in normal dogs and dogs with focal, radiation-induced
      brain lesions. A dose of 20 Gy was delivered to a point 0.75 cm from a removable
      interstitial 125I source; parameters relating to blood flow and permeability were
      quantified using computed tomography 2-8 weeks after irradiation. Blood flow
      related endpoints included regional cerebral blood flow (rCBF), mean transit time
      of blood and vascular volume, while endpoints related to permeability included
      blood-to-brain transfer constant (Ki), brain-to-blood transfer constant and
      plasma volume. In unirradiated brain, an i.v. bolus of RMP-7 administered through
      the left cephalic vein induced a rapid and transient hypotension and a
      statistically significant increase in vascular volume; no alterations in any
      parameter related to permeability were observed. After irradiation, changes in
      rCBF after RMP-7 depended upon time after exposure, effects presumably due to
      changing morphology in the irradiated tissues. In the radiation lesions,
      significant increases in Ki were observed 5 minutes after injection of RMP-7, but
      those increases were not related to time after irradiation or alteration in blood
      flow-related parameters. Our results showed that RMP-7 selectively increased
      permeability in already damaged vasculature without affecting the extent or
      volume of radiation-induced vasogenic edema. These data suggest that RMP-7 may
      provide an effective means to enhance the delivery of compounds to an already
      compromised brain while not exacerbating the potential adverse effects of pre
      existing vasogenic edema.

PMID- 9524079
TI  - Adenovirus-mediated p53 gene delivery potentiates the radiation-induced growth
      inhibition of experimental brain tumors.
AB  - Patients with malignant gliomas continue to have very poor prognosis even after
      surgical resection, radiation and chemotherapy. Because these tumors often have
      alterations in the p53 tumor suppressor gene, which plays a key role in the
      cellular response to DNA damaging agents, we investigated the role of p53 gene
      therapy in conjunction with ionizing radiation in a rat brain tumor model.
      Exposure of cultured rat 9L gliosarcoma cells, which contain a mutant p53 gene,
      to a recombinant adenovirus-vector bearing the wild-type p53 gene (Adp53),
      induced apoptosis within 24 hours. Although ionizing radiation had no additional
      effect on apoptosis within this time frame, it caused G1 arrest in non-apoptotic
      cells after Adp53 therapy. In contrast, wild-type 9L cells demonstrated little G1
      arrest after X-irradiation. When animals bearing brain tumors were irradiated
      after intratumoral Adp53 injections, more than 85% reduction in tumor size was
      noted. Moreover, the group of rats receiving both radiation and Adp53 therapy had
      a significant increase in survival as compared to animals receiving either
      therapy alone. These results support the use of p53 gene therapy as an adjunct to
      radiation in treatment of malignant brain tumors.

PMID- 9524080
TI  - Detection of p21WAF1/Cip1 in brain metastases.
AB  - The p21WAF1/Cip1 (p21) protein, a negative regulator of G1 checkpoint control,
      was overexpressed in the majority of human gliomas. To investigate whether p21
      expression in brain metastases from various systemic origins is similar to that
      in gliomas and whether p21 expression is regulated differently in brain
      metastases and in corresponding primary tumors, we used immunohistochemical
      staining to examine the expression of p21 in paraffin-embedded sections prepared
      from primary colon and breast carcinomas and from metastatic brain tumors that
      originated from colon, breast, lung, and kidney cancers and from melanoma. Our
      results showed that 56% (28 of 50) of the brain metastases samples have more than
      1% p21-positive staining cells compared with 87% of primary gliomas reported
      previously. Among the samples analyzed, p21 expression in brain metastases from
      breast carcinomas was much higher than in primary breast carcinomas. In contrast,
      p21 expression in brain metastases from colon carcinomas was less than primary
      colon carcinomas. The results from this pilot study suggest that p21 expression
      is regulated differently in metastatic and primary tumors.

PMID- 9524081
TI  - An attempt to treat pediatric intracranial alphaFP and betaHCG secreting germ
      cell tumors with chemotherapy alone. SFOP experience with 18 cases. Societe
      Francaise d'Oncologie Pediatrique.
AB  - PURPOSE: Intracranial alphaFP and betaHCG secreting germ cell tumors have a very
      poor prognosis with local treatment alone. Because of efficacy of chemotherapy in
      extracranial forms, we tried in the SFOP (Societe Francaise d'Oncologie
      Pediatrique) to treat them with chemotherapeutic treatment exclusively. PATIENTS
      AND METHODS: Eighteen patients (10 alphaFP, 2 betaHCG, 6 alphaFP and betaHCG
      secretion) were enrolled from January 1988 to December 1992. After biological
      diagnosis patients were to receive 6 cycles of chemotherapy (vinblastine
      bleomycin - carboplatin or etoposide - carboplatin/ifosfamide - etoposide). After
      completion of chemotherapy, surgery was to be performed in case of residual
      tumor. Focal radiation was only to be delivered in case of viable residual tumor.
      RESULTS: All patients had biological remission and tumor reduction. Fifteen
      patients were treated according to the protocol by chemotherapy alone (13) or
      chemotherapy and radiation of residue (2). Twelve of the 13 non irradiated
      patients relapsed, 8 in local and/or regional area, 3 in cerebrospinal area and 1
      in undeterminated area with mild elevation of markers except in one case. Six
      patients are alive in second complete remission after chemotherapy and/or surgery
      and then a consolidation treatment with radiation and/or high dose chemotherapy
      (5) or craniospinal radiation (1). Three patients received radiation after 2 or 3
      cycles of chemotherapy as protocol violations and didn't relapse. Thus, 12
      patients out of the 18 patients are alive with a median follow up of 68 months.
      All but 1 had focal radiation as part of treatment. No toxic death was observed.
      CONCLUSION: Although survival rate is noteworthy (66%), these tumors were not
      curable with this conventional chemotherapy alone and focal radiotherapy should
      be part of the treatment.

PMID- 9524082
TI  - Incidence studies of primary and secondary intracranial tumors: a systematic
      review of their methodology and results.
AB  - We reviewed the incidence studies of intracranial tumors to compare their
      methodology and identify whether there was evidence of true differences in
      incidence by time, place, age, or sex. Studies were identified from Medline (1966
      95), bibliographies of relevant articles, and personal knowledge. For each study,
      various methodological details were recorded, along with the age-standardized
      incidence of all primary tumors and the crude and age/sex-specific incidences of
      different types of intracranial tumor. Methodological factors which significantly
      influenced the reported incidence were identified and the results of different
      studies were compared and combined in a meta-analysis if appropriate. Twenty
      studies (over 20,000 primary tumors) were included. Higher incidences of primary
      tumors were found in studies that: used many methods to identify cases (odds
      ratio [OR] 1.92); included a high percentage of asymptomatic patients (OR 2.03);
      did not require histologic confirmation of the diagnosis (OR 1.69). Studies from
      the 1980's reported higher incidences than in previous decades (OR 1.51),
      probably because of improved methodology. Comparable studies from the 1980's gave
      widely different incidence rates for all primary tumors (7.1-18.6 per 100,000 per
      year). In all studies, the incidence of neuroepithelial and meningeal tumors
      increased dramatically with age. Neuroepithelial tumors were 40% more common in
      men, whilst meningeal and cranial nerve tumors were about 80% and 40% more common
      in women, respectively. Further incidence studies are required to establish
      geographical and secular variations in the incidence of primary intracranial
      tumors but these must use comparable methodologies. Provisional guidelines for
      future studies are given.

PMID- 9524083
TI  - Multiple causes of cerebrovascular events in children with tumors of the
      parasellar region.
AB  - Cerebrovascular arterial occlusion is a rare but devastating event causing long
      term morbidity in children with tumors in the parasellar region. While usually
      associated with radiation therapy, there are a variety of host, tumor and
      treatment factors which predispose patients to significant vasculopathy. Case
      reports of 5 patients from St. Jude Children's Research Hospital with tumors in
      the parasellar region who presented with or developed vascular occlusive disease
      are summarized. Multiple factors are identified in these cases which probably
      impacted on the development of cerebral arterial occlusion with or without
      moyamoya syndrome. These include, but are not limited to, neurofibromatosis,
      tumor encasement of major cerebral vessels, surgical alterations, and radiation
      therapy. The literature supports multiple, potentially interactive etiologies for
      the development of vascular events in these patients, suggesting that their
      development is not simply a phenomenon related to radiation therapy.

PMID- 9524084
TI  - Cisplatin/vincristine chemotherapy for hypothalamic/visual pathway astrocytomas
      in young children.
AB  - Hypothalamic/visual pathway astrocytomas in children are usually quiescent, but
      certain cases contain aggressive neoplasms that cause progressive neurological
      and visual deterioration. Radiotherapy is not recommended in young children
      because of its adverse effects later in life. This report describes the efficacy
      of a chemotherapeutic regimen. Four young children with hypothalamic/visual
      pathway astrocytoma, with a mean of 18 months of age at diagnosis, were treated
      with chemotherapy. Three patients had diencephalic syndrome at the disease's
      onset. Three patients with pilocytic astrocytoma were histologically verified,
      and another infant was clinically diagnosed. A combination chemotherapy using
      cisplatin and vincristine was administered in a total of 8 cycles in 3 children
      and 4 in one child. One patient who demonstrated renal insufficiency after 4
      cycles of this regimen was treated with additional 4 cycles using carboplatin
      instead of cisplatin. The acute and subacute hematologic and otologic toxicities
      were mild, and a transient renal insufficiency in a child during chemotherapy
      improved. After chemotherapy, tumor regression was documented in 3 patients, and
      the disease was observed to be stable in one patient with an evidence of
      intratumoral necrosis on MRI. Three patients showed neurological and
      endocrinological improvements. These results suggest that this regimen is
      feasible in young children and may be useful as a first-line treatment for
      hypothalamic/visual pathway astrocytomas, which in turn may allow potentially
      deleterious irradiation on the maturing brain to be deferred until the disease
      progresses.

PMID- 9524085
TI  - Leptomeningeal metastases: a review of evaluation and treatment.
AB  - Leptomeningeal metastases (LM) is a common problem in neuro-oncology occurring in
      approximately 5% of all patients with cancer. Notwithstanding frequent focal
      signs and symptoms in LM, LM is a disease affecting the entire neuraxis and
      therefore staging and treatment need encompass all cerebrospinal fluid (CSF)
      compartments. Central nervous system (CNS) staging of LM includes contrast
      enhanced cranial computerized tomography (CE-CT) or magnetic resonance imaging
      (MR-Gd), contrast enhanced spine magnetic resonance imaging (MR-S) or
      computerized tomographic myelography (CT-M) and radionuclide CSF flow study (FS).
      Treatment of LM involves involved-field radiotherapy of bulky or symptomatic
      disease sites and intra-CSF drug therapy. The inclusion of concomitant systemic
      therapy may benefit patients with LM and may obviate the need for intra-CSF
      chemotherapy. At present, intra CSF drug therapy is confined to three
      chemotherapeutic agents (i.e. methotrexate, cytosine arabinoside and thio-TEPA)
      administered by a variety of schedules either by intralumbar or intraventricular
      drug delivery. Although treatment of LM is palliative with an expected median
      patient survival of 6 months, it often affords stabilization and protection from
      further neurologic deterioration in patients with LM.

PMID- 9524086
TI  - Bone marrow metastasis in astrocytic gliomata.
AB  - With the increasing survival time of many pediatric patients with malignancies,
      unexpected symptoms or signs require diligent search for rare complications or
      second cancers related to the disease or treatment. We recently encountered a
      patient with extensive glioblastoma multiforme who developed pancytopenia six
      months after completion of treatment with craniospinal radiation and chemotherapy
      with etoposide and cyclophosphamide. Bone marrow aspirate and biopsy confirmed
      bone marrow metastasis from the brain tumor. He showed good partial remission
      with chemotherapy with carmustine and cis-platinum as demonstrated by serial bone
      marrow aspirate for cytology and cytogenetics and enjoyed good quality of life
      for eight months. 14 other patients with astrocytic glioma, two of whom are
      children, are reported in the literature to have diffuse bone marrow metastasis.
      Therefore, in patients with malignant astrocytic tumor, bone marrow metastasis,
      though not common, should be considered when bone pain or cytopenias occur,
      especially when prolonged.

PMID- 9524087
TI  - Inhibitory effects of phenylbutyrate on the proliferation, morphology, migration
      and invasiveness of malignant glioma cells.
AB  - The purpose of this study was to characterize the effects of sodium 4
      phenylbutyrate (phenylbutyrate) on the proliferation, morphology, migration and
      invasiveness of malignant glioma cells in vitro. Phenylbutyrate is a novel
      differentiating and cytotoxic compound used clinically with low toxicity in the
      treatment of beta-thalassemia, sickle cell anemia and urea cycle disorders.
      Preliminary clinical trials testing phenylbutyrate as an anti-cancer agent have
      included patients with malignant glioma. However, little information is available
      regarding the effects of phenylbutyrate on glioma cells, particularly with
      respect to the expression of genes important in the pathogenesis of glial
      malignancy. In experiments reported here, glioma cell lines and explant cells
      from a tumor patient were exposed to 2, 4 and 8 mM phenylbutyrate and compared to
      untreated control cells. The effect on cellular proliferation was assessed using
      cell counts and DNA flow cytometry. Changes in morphology were evaluated using
      vimentin staining. Scratch and Matrigel assays were performed to assess changes
      in cellular migration and invasiveness. Finally, Northern blot analysis was used
      to study c-myc and urokinase expression. Phenylbutyrate was found to have dose
      dependent inhibitory effects on glioma cell proliferation, morphology, migration,
      invasiveness and c-myc and urokinase expression. Mean growth-inhibitory (IC50)
      phenylbutyrate concentrations ranged from 0.5 mM for T98G cells to 5.0 mM for
      explant cells. Phenylbutyrate treatment reduced % S phase cells, increased %
      G0/G1 cells, and produced morphologic changes consistent with induction of
      differentiation. 24 hours of treatment with 4 mM phenylbutyrate resulted in a 50%
      reduction in migration and invasiveness. Northern blots showed a decrease in
      urokinase and c-myc expression at non-cytotoxic doses. We conclude that
      phenylbutyrate is a promising candidate compound for treating patients with
      malignant glioma.

PMID- 9524088
TI  - Vinca-alkaloid neurotoxicity measured using an in vitro model.
AB  - Neurotoxicity forms a major limitation in many clinical applications of
      vincristine and other powerful vinca alkaloid anticancer drugs. Using the nerve
      growth factor (NGF) dependent neurite outgrowth from the PC12 pheochromocytoma
      cell line as an in vitro assay for neurotoxicity, the effect of different
      concentrations of vincristine (0.55; 1.1 and 11 nM) was compared with that of
      vindesine and vinblastine. Vincristine in comparatively low concentration (0.55
      nM) could significantly decrease the percentage of neurite forming cells from 74%
      to 32% within a three day incubation period. Especially the longer neurites (> 2
      x cell body) proved to be extremely sensitive for vincristine effects.
      Vinblastine and vindesine were also able to decrease, dose dependently and
      significantly, the percentage of neurite forming cells. However, the effects
      observed were less severe than that of vincristine. The sequentially increasing
      level of neurotoxicity due to vinblastine, vindesine and vincristine, as observed
      in the neurite outgrowth inhibition correlates well with previous findings from
      animal models and with data from the clinical practice. Withdrawal of vincristine
      resulted in a rapid restoration of neurite formation, suggesting the potential
      reversibility of neurotoxic effects in these cells. These results provide a
      validation of the PC12 neurite outgrowth assay as a suitable and reliable model
      for predicting neurotoxicity.

PMID- 9524089
TI  - In vitro study on intrathecal use of 5-fluoro-2'-deoxyuridine (FdUrd) for
      meningeal dissemination of malignant brain tumors.
AB  - We investigated 5-fluoro-2'-deoxyuridine (FdUrd) as a potential agent for
      intrathecal treatment of malignant brain tumors with meningeal dissemination. We
      examined the neurotoxicity of FdUrd in vitro using primary cultures of neurons
      from C57BL/6 mice (ED14). Tumoricidal activity was also studied in four glioma
      cell lines and one medulloblastoma cell line. In addition, thymidine
      phosphorylase (TPase) and thymidine kinase (TK), which are key enzymes for FdUrd
      metabolism, were measured in the cerebrospinal fluid (CSF) of 36 patients with
      brain tumors. The antitumor activity of FdUrd for murine glioma cells was
      approximately 20- to 200-fold higher than that of 5-fluorouracil (5-FU). Against
      human cell lines, it was 3- to 500-fold higher than that of 5-FU. The neurotoxic
      effect of FdUrd on cultured neurons was far less than that of 5-FU or 5
      fluorouridine (FUrd). Cerebrospinal fluid contained no detectable thymidine
      phosphorylase in most patients with brain tumors. Several studies have indicated
      that FdUrd is rapidly converted to 5-FU in the presence of thymidine
      phosphorylase, so that a high dose of FdUrd must be administered to obtain good
      efficacy. However, a high dose FdUrd frequently cause severe toxicity. In
      contrast, the data obtained here suggest that no enzymatic conversion of FdUrd to
      5-FU should occur in the CSF. In addition, FdUrd has an excellent antitumor
      activity and minimal neurotoxicity. We therefore conclude that intrathecal FdUrd
      is a potential therapy for CSF dissemination of malignant brain tumors.

PMID- 9524090
TI  - Exophytic malignant brainstem mixed glioma in an adult: a case report.
AB  - Anaplastic mixed gliomas are rare tumors that occur mostly in the cerebral
      hemispheres. They have a distinctive histological appearance characterized by the
      presence of two or more glial cellular constituents. The incidence of malignant
      mixed glioma of the brainstem and posterior fossa is extremely low. The authors
      report an unusual case of an exophytic malignant mixed glioma. Following subtotal
      resection, the patient received conventional radiotherapy, but continued to
      deteriorate, and died five months after surgery. The extensive literature review
      focuses on histopathology, clinical features, natural history, and possible
      treatment modalities of this unusual neoplasm.

PMID- 9524091
TI  - Intracranial ependymoma in the adult patient: successful treatment with surgery
      and radiotherapy.
AB  - PURPOSE: Ependymoma is an uncommon intracerebral tumor in adults. Since the site
      of origin frequently prevents complete surgical removal, adjunctive radiotherapy
      is used to destroy residual disease. We present our experience in treating 10
      adults with intracranial ependymoma. METHODS: Five men and 5 women were treated
      in the past 16 years. The median age was 38 (range 24-69). All had contrast
      enhanced CT or MRI showing the extent of the tumor. One patient had total
      excision while the remainder had subtotal removal. Radiation therapy was
      delivered to the tumor bed with a 1-2 cm margin of normal tissue generally at 180
      200 centiGray (cGy) per treatment once a day. Total dose ranged from 5400 to 7200
      cGy. Two patients received experimental treatment with 100 cGy delivered twice a
      day for total of 6800 and 7200 cGy respectively. Four patients received initial
      treatment to a large field with a subsequent boost to the tumor bed. One patient
      received his entire course of treatment via this large field. RESULTS: With a
      median follow-up of 64 months, 7 patients are alive and free of disease while 2
      died of intercurrent disease, without evidence of tumor, at 7 and 9 years
      following treatment. Another patient died 1 1/2 years after treatment of unknown
      causes. CONCLUSION: We conclude that postoperative radiotherapy is effective in
      preventing regrowth of intracranial ependymoma following subtotal resection in
      adults. Treatment fields should cover the initial tumor bed with a 1-2 cm margin
      to avoid long term radiation damage.

PMID- 9524093
TI  - Evaluation of modern pathologic nomenclature, tumor imaging and treatment of
      pituitary adenomas in a recent surgical series.
AB  - This study reviews retrospectively 49 patients with pituitary adenomas, using a
      modern, immunohistochemically and ultrastructurally-based nomenclature. It also
      compares tumor imaging by CT and MRI scans, and analyzes the results of recent
      neurosurgical and radiotherapeutic treatments. Based on the findings of the
      study, several recommendations on clinical management of pituitary macroadenoma
      are made.

PMID- 9524094
TI  - Response of recurrent glioblastoma and anaplastic astrocytoma to dibromodulcitol,
      BCNU and procarbazine--a phase-II study.
AB  - Twenty six (17 males) patients with glioblastoma (GBL), median age 55 years,
      median Karnofsky Index (KI) 70/100, and 11 patients (9 males) with anaplastic
      astrocytoma (AA), median age 56 years, median KI 70/100 were treated at
      recurrence with dibromodulcitol (DBD) 1400 mg/m2 on day 1, BCNU 150 mg/m2 on day
      2, and procarbazine (PCZ) 150 mg/day on days 1 to 15. The course was repeated
      every 4 weeks, but was delayed or decreased by 25% according to hematological
      toxicity. Response to treatment was evaluated by the criteria of MacDonald et al.
      (J Clin Oncol 1990; 8: 1277-1280). All GBL-patients were followed until death.
      One patient with complete response (CR) survived one year, and 2 patients with
      partial response (PR) survived 1 and 3 years. Ten patients who stabilized (SD)
      survived 7.5 months, and 13 patients who progressed under chemotherapy had a
      median survival of 3.5 months. In AA-group 3 patients were alive at the time of
      the analyses. Six patients: 1 CR and 5 PR survived 6 to 40+ months. Two patients
      with SD survived 4 and 14 months. Three patients with progressive disease had a
      mean survived of less than 3 months. The response rate of 55% in AA was
      significantly higher (p = 0.011) than the 12% response rate seen in GBL. We
      conclude that the regimen tested appears particularly promising in AA. The
      results in GBL are comparable to those obtained with a single nitrosourea,
      despite an increased but reversible toxicity.

PMID- 9524092
TI  - Survival following intensive chemotherapy with bone marrow reconstitution for
      children with recurrent intracranial ependymoma--a report of the Children's
      Cancer Group.
AB  - Recurrent intracranial ependymoma is rarely cured by surgery, radiotherapy, and
      chemotherapy in conventional doses. This study was designed to determine the
      toxicity, radiographic response rate and outcome following intensive chemotherapy
      with ThioTEPA, etoposide, carboplatinum and autologous bone marrow rescue (ABMR)
      for young children with recurrent central nervous system ependymoma. ThioTEPA 300
      mg/m2/day (total 900 mg/m2) and etoposide 250 to 500 mg/m2/day (total 750 to 1500
      mg/m2) were administered for three consecutive days with or without the addition
      of carboplatinum 500 mg/m2/day (total 1500 mg/m2) for an additional three
      consecutive days, and autologous bone marrow was reinfused 72 hours following
      chemotherapy. Eligibility criteria required adequate renal, hepatic and pulmonary
      function, and no tumor infiltration of bone marrow. Fifteen children with
      recurrent intracranial ependymoma, aged 5 months to 12 years (median 22 months),
      were treated. Five patients died of treatment related toxicities within 62 days
      of marrow reinfusion. Eight have expired from progressive disease a median of six
      months post-ABMR, and one has died from unrelated causes. One child remains alive
      25 months post-ABMR, following further disease recurrence. No partial or complete
      responses were observed. This regimen of high-dose ThioTEPA and etoposide with or
      without additional carboplatinum with ABMR is not an effective strategy for
      retrieving heavily pre-treated children with recurrent ependymoma.

PMID- 9524095
TI  - Aggressive treatment with complete remission in primary diffuse leptomeningeal
      gliomatosis--a case report.
AB  - Primary leptomeningeal gliomatosis is rare, and the diffuse form (PLDG) is even
      more unusual. The following report is an example. A 17 year-old man developed a
      syndrome characterized by extensive basal and chronic spinal meningitis. Routine
      biological tests showed elevated levels of CSF proteins, and moderate mononuclear
      pleocytosis, with no direct evidence of neoplasia, leading to a diagnosis of
      chronic meningitis. A second meningeal biopsy, guided by MRI and performed in the
      left frontal region, led to the specific diagnosis of primary diffuse
      leptomeningeal gliomatosis. Treatment including ventricular and lumbar shunting,
      a course of cortico-spinal radiation, and three courses of an eight-drug systemic
      chemotherapy with intrathecal methotrexate lead to complete remission over 15
      months. We believe that this is the first report of such a remission in the
      literature.

PMID- 9524096
TI  - High dose oral tamoxifen and subcutaneous interferon alpha-2a for recurrent
      glioma.
AB  - Chemotherapeutic regimens in present use for recurrent glioma have substantial
      toxicity. Activity against recurrent gliomas has been reported for both tamoxifen
      and interferon alpha, agents that have more acceptable toxicity profiles and that
      can be administered in an outpatient setting. We tested the efficacy and toxicity
      of the combination of high-dose tamoxifen and interferon alpha in adults with
      recurrent glioma in a phase II trial. Eligible patients had radiographically
      measurable recurrent gliomas of any grade after initial radiation therapy.
      Interferon-alpha [6 x 10(6) U subcutaneously three times per week] and tamoxifen
      (240 mg/m2/day orally) were administered continuously. Treatment response was
      assessed at 6 week intervals using clinical and radiographic criteria. Eighteen
      patients (11 males and 7 females) were enrolled. Median age was 41 years (range
      23-61 years). All patients had gliomas that progressed after radiation therapy
      and nitrosourea chemotherapy. The histologic diagnosis of the original tumor was
      glioblastoma multiforme in 8 patients, anaplastic astrocytoma in 5 patients,
      astrocytoma in 4 patients and mixed malignant glioma in 1 patient. Reversible
      moderate to severe neurological toxicity manifested by dizziness and unsteady
      gait was seen at tamoxifen doses of 240 mg/m2/day. Although the initial tamoxifen
      dose was reduced to 120 mg/m2/day, moderate neurotoxicity was noted at this dose
      as well and the trial was closed early. The combination of oral tamoxifen (120 to
      240 mg/m2/day) and subcutaneous interferon-alpha [6 x 10(6) U three times per
      week] was associated with significant neurotoxicity in this group of recurrent
      glioma patients, resulting in early study closure. Of 16 evaluable patients, 12
      had progressive disease after one cycle of treatment, 3 had stable disease, and
      there was one minor response. Gradual dose escalation may be required if similar
      patients are to be treated with high dose tamoxifen in conjunction with
      interferon.

PMID- 9524098
TI  - Unexpected in vitro chemosensitivity of malignant gliomas to 4
      hydroxyperoxycyclophosphamide (4-HC).
AB  - To individually tailor chemotherapy for patients with malignant gliomas according
      to tumor chemosensitivity, a rapid assay system which can be performed with a
      high success rate is needed. The fluorescent cytoprint assay (FCA) can assess
      multiple chemotherapeutic agents using small (approximately 500 cells) tumor
      aggregates very quickly (approximately 1 wk). Tissue samples from 51 patients
      with malignant gliomas obtained either at time of initial diagnosis (n = 34) or
      at recurrence were assayed using this method. The assay success rate approached
      90% in those culture samples which were histologically verified as tumor. A
      meaningful number of agents could be tested both on samples obtained by
      stereotactic biopsy (median, 5) and on specimens from more extensive resections
      (median, 6). One hundred ninety-three FCAs were performed on a samples obtained
      from 36 patients. In only twenty six assays (14%) was an agent deemed sensitive
      (> 90% cell kill) to a chemotherapeutic agent. Sixty-two percent of sensitive
      FCAs were observed in tumors tested against the activated analog of
      cyclophosphamide, 4-hydroxyperoxycyclophosphamide (4-HC), where a sensitivity
      rate (# samples sensitive/total tested against agent) of 64% (95 % CI, 36.6
      77.9%) was noted. This rate was significantly higher than with any other agent
      tested (p = 0.012, two sided McNemar's test) and was not affected by age,
      histology or disease status. We conclude that: (1) the FCA represents a feasible
      method for quickly assaying tumors for sensitivity to multiple chemotherapeutic
      agents; and (ii) malignant gliomas may be particularly sensitive to 4-HC.

PMID- 9524097
TI  - Malignant meningioma: an indication for initial aggressive surgery and adjuvant
      radiotherapy.
AB  - Malignant meningiomas constitute a rare subset of meningiomas and display a
      marked propensity for postsurgical recurrence. This retrospective study evaluates
      the various parameters which alter the recurrence rate. The records of all
      malignant meningioma patients treated from 1984 through 1992 were reviewed, and
      the time to recurrence or current patient status was determined, and the
      influence of various patient and disease parameters were analyzed. Thirty-eight
      patients were treated with 48 malignant meningioma resections performed (28 total
      and 20 subtotal), 25 at initial presentation and 23 for recurrent disease; 19
      patients received postoperative radiotherapy. Subtypes included 32 anaplastic
      meningioma, 11 hemangiopericytoma, 2 meningiosarcoma, and 3 papillary meningioma.
      Followup ranged from 3 to 144 months, with five patients excluded from analysis.
      Actuarial disease free/progression free survival (DFS) at 5 years was 39%
      following total resection versus 0% after subtotal resection (p=0.001). For all
      totally excised lesions, the 5-yr DFS was improved from 28% for surgery alone to
      57% with adjuvant radiotherapy (p=NS). Adjuvant irradiation following initial
      resection increased the 5-yr DFS rates from 15% to 80% (p=0.002). When
      administered for recurrent lesions, adjuvant radiotherapy improved the 2-yr DFS
      from 50% to 89% (p=0.015), but had no impact on 5-yr DFS. Multivariate analysis
      indicates extent of resection, adjuvant radiotherapy, and recurrence status are
      independent prognostic factors. Malignant meningiomas display a tendency for post
      surgical recurrence, with recurrence significantly increased for multicentric and
      recurrent disease. Complete surgical resection and the administration of adjuvant
      irradiation following initial resection are crucial to long-term control.

PMID- 9524100
TI  - 5-Fluorocytosine-mediated apoptosis and DNA damage in glioma cells engineered to
      express cytosine deaminase and their enhancement with interferon.
AB  - To explore the antitumor mechanism of bacterial cytosine deaminase plus 5
      fluorocytosine (CD/5-FCyt) in combination with interferons (IFNs), glioma cells
      were transduced with recombinant retroviruses expressing CD. The transduced
      glioma cells become sensitive to the nontoxic prodrug 5-FCyt. Apoptosis, DNA
      damage, bystander effect, and inhibition of thymidylate synthase (TS) and DNA
      synthesis are associated with CD/5-FCyt-mediated glioma cell killing.
      Furthermore, IFNs enhance this effect by increasing DNA damage and further
      inhibiting TS activity. The bystander effect is mediated by the release of
      cytotoxic metabolites of 5-FCyt into the extracellular milieu triggering
      apoptosis and DNA damage. Our data indicate that the use of CD/5-FCyt in
      combination with IFNs may provide a more effective approach for the treatment of
      brain tumors.

PMID- 9524099
TI  - Expression of a receptor protein tyrosine phosphatase in human glial tumors.
AB  - We have analyzed expression of a receptor protein tyrosine phosphatase
      (RPTPzeta/beta) in tissue samples from 23 human gliomas. Using the reverse
      transcription-polymerase chain reaction (RT-PCR) technique, we assayed for the
      presence or absence of mRNA transcripts encoding the intact receptor and 2
      alternatively spliced forms of RPTPzeta/beta. Transcripts encoding the intact and
      truncated receptors were expressed in all of the lower grade gliomas (WHO grade 1
      3) analyzed, but not in 55% of the grade 4 glioblastomas multiforme (GBM).
      However, this subset of GBMs did express an alternatively spliced secreted form
      comprised of only the RPTPzeta/beta extracellular domain. Our data suggests there
      may be a correlation between the loss of transcripts encoding the receptor forms
      of RPTPzeta/beta and progression from low to high grade gliomas. This work
      provides additional evidence for the importance of phosphatase isoform expression
      in human tumors.

PMID- 9524101
TI  - Can experimental models of rodent implantation glioma be improved? A study of
      pure and mixed glioma cell line tumours.
AB  - To evaluate the hypothesis that co-implantation of different rodent glioma cell
      lines might result in experimental brain tumours that more closely resemble human
      gliomas the neuropathology and immunocytochemical features of implantation
      gliomas derived from single cell lines (C6, A15A5, F98), two cell lines admixed
      50:50 prior to implantation (C6 + F98 and C6 + A15A5) and three cell lines
      equally admixed (C6 + A15A5 + F98) was studied in the adult Wistar rat. Tumours
      grew consistently following implantation of the single and the two admixed cell
      lines, however tumour growth following triple mix implantation was considerably
      and consistently impaired. The tumours derived from admixed cell lines showed
      regional heterogeneity with areas characteristic of both the primary cell lines.
      Foci of lymphocytic infiltrates, tumoural necrosis, often with pseudopallisading,
      and peritumoural edema were consistent features of all tumours. Limited
      parenchymal and more extensive perivascular tumoural invasion was seen
      predominantly in tumours containing the C6 cell line. There were no significant
      differences in GFAP, vimentin and HSP70 staining between the mixed tumours,
      although the pure F98 and A15A5 tumours were, unlike the pure C6 gliomas, S-100
      negative. Using PCNA expression as a measure of the tumour proliferation all
      except the tumours derived from the three cell lines mix, which had a staining
      index of 7-10%, had focal staining indices in viable tumour of between 40-80%.
      There was focal positive staining in both perilesional brain and in regions of
      all tumours for the macrophage markers ED-1 and ED-2. None of the three cell
      lines stained in vitro for either ED1 and ED2 but all were constitutively
      positive in vitro for OX-6, a proposed marker for antigen presenting cells. The
      macrophage and lymphocytic response suggest a vigorous but largely ineffective
      immunological response had been mounted against all tumours. The consistent
      failure of the triple mix tumours to grow is unexplained. This work has shown the
      feasibility of producing 'mixed' cell line experimental gliomas by combining two
      cell lines at the time of innoculation. However, the relative failure to produce
      (i) mixed tumours that have properties not inherent to either parent cell line
      and (ii) implantation glioma with three cell lines suggest there are limits to
      this approach. Admixture of cell lines at the time of implantation therefore does
      not make experimental glioma models that more closely resemble natural gliomas,
      and also has some particular disadvantages. This experimental approach is
      therefore not recommended for use in the study of tumour biology and in
      evaluating the effectiveness of novel therapies.

PMID- 9524102
TI  - Iatrogenic seeding of anaplastic astrocytoma following stereotactic biopsy.
AB  - We present a case of probable tumor seeding along the needle tract following
      computer tomography-guided stereotactic biopsy of an anaplastic astrocytoma in a
      23 year old male. Six months after the initial biopsy and 3 months following a
      second stereotactic procedure for cyst aspiration, a second lesion appeared
      directly along the biopsy trajectory at a distance from the primary tumor. This
      lesion is presumed to be recurrent tumor and appears to have been spread
      iatrogenically following the biopsy of the initial tumor and the subsequent cyst
      aspiration along the same tract.

PMID- 9524103
TI  - Malignant gliomas of the cerebellum: an analytic review.
AB  - Using an analytical review, the demographic data on malignant cerebellar gliomas
      such as length of survival, and those factors associated with prolonged survival
      were examined. Seventy-one cases of malignant cerebellar glioma reported since
      1975 were combined and reviewed with the seven cases treated at our institution
      since that time. Thirty-seven patients (47%) had grade III tumors and 41 (53%)
      had grade IV tumors. Fifty-nine percent of the tumors were located in the
      hemispheres and 41% were found in the vermis. Median survival for patients with
      grade III anaplastic astrocytomas was 32 months compared to 11 months for those
      with grade IV glioblastomas multiforme (P = 0.0257). For the entire cohort,
      patients with grade III tumors, those who had a surgical resection, and those
      that had received radiation therapy for treatment of their tumor had prolonged
      survival on multivariable analysis. Radiation therapy was associated with
      extended survival for patients with grade III tumors by uni- and multivariate
      analysis. For grade IV tumors, univariate analysis revealed prolonged survival
      for those patients who had surgical resection compared to those who had biopsy
      alone (P = 0.0036) and for those who received external beam radiation therapy (P
      = 0.0001). Patients with malignant gliomas of the cerebellum had length of
      survival comparable to their supratentorial counterparts. Prompt diagnosis and
      treatment may explain the similarity in survival found between supra- and
      infratentorial malignant gliomas despite an expected shorter survival because of
      treatment limitations. Surgical resection followed by radiation therapy is
      recommended for patients with malignant gliomas of the cerebellum.

PMID- 9524105
TI  - Schwannomas limited to the infratemporal fossa: report of two cases.
AB  - Schwannomas limited to the infratemporal fossa are rare lesions that may also
      involve the maxillary sinus, the orbit and the retropharyngeal space. We present
      two cases of schwannoma arising from the extradural divisions of the trigeminal
      nerve, with corresponding areas of sensory loss. Both patients had been operated
      for spinal canal schwannomas previously. Complete tumor removal was accomplished
      in both cases. The schwannoma of the maxillary division was excised using an
      orbitozygomatic extradural approach. The schwannoma of the mandibular division
      was excised using a subtemporal-infratemporal approach. Trigeminal nerve function
      was preserved and complete recovery of function was achieved in each patient.
      Identification of an infratemporal schwannoma should alert the physician to
      consider the diagnosis of neurofibromatosis. The literature regarding schwannomas
      limited to the infratemporal fossa is reviewed.

PMID- 9524104
TI  - Primary rhabdomyosarcoma of the brain: observations on a case with clinical and
      radiological evidence of cure.
AB  - Cerebral rhabdomyosarcoma is a highly aggressive tumor with poor prognosis
      affecting children and, rarely, adults. The authors describe the case of a
      patient treated for primary fronto-parietal embryonal rhabdomyosarcoma with a
      long survival (30 months after surgery) and no clinical or radiological evidence
      of recurrence and discuss the chemotherapy applied in this case.

PMID- 9524106
TI  - Tracer transport and metabolism in a patient with juvenile pilocytic astrocytoma.
      A PET study.
AB  - We studied a patient with juvenile pilocytic astrocytoma (JPA) using positron
      emission tomography (PET), 18F-fluorodeoxyglucose (FDG), 11C-methionine (MET),
      and 82Rubidium (RUB). Non-linear fitting and multiple time graphical plotting of
      the dynamic PET data revealed values for tumor plasma volume, blood-brain barrier
      transport rate constants and tracer distribution volume in the range of
      glioblastomas and meningiomas, or higher. Likewise, the steady-state accumulation
      of MET and FDG was increased. With regard to the known vascular composition of
      JPA, our data suggest that increased transport and distribution considerably
      contribute to the high net tracer uptake observed in this tumor.

PMID- 9524107
TI  - Cerebral edema associated with meningiomas: the role of peritumoral brain tissue.
AB  - We undertook a morphological study of small pieces of peritumoral brain tissue
      removed from seven patients with meningiomas submitted to surgery. All patients
      had cerebral edema, as shown by preoperative C.T. and N.M.R.. Control specimens
      were obtained from five patients undergoing ventriculo-peritoneal shunt. The
      tissue fragments were fixed in glutaraldehyde-osmium and embedded in Epon. In
      semi-thin sections observed under light microscopy peritumoral endothelial cells
      exhibited voluminous cytoplasm and nucleus. Morphometrical evaluation confirmed
      that these endothelial cell nuclei were significantly larger than controls. Under
      the electron microscope those cells showed nuclei rich in euchromatin and
      cytoplasm rich in pinocytotic vesicles. The morphological changes observed
      suggest a process of dedifferentiation of brain peritumoral capillary cells and
      are compatible with an increase in permeability. Both events, which may be due to
      diffusion of a tumoral vascular permeability factor, favour the hypothesis that
      peritumoral brain tissue contributes to edema fluid that accumulates around
      meningiomas.

PMID- 9524109
TI  - Genetic selection of intragenic suppressor mutations that reverse the effect of
      common p53 cancer mutations.
AB  - Several lines of evidence suggest that the presence of the wild-type tumor
      suppressor gene p53 in human cancers correlates well with successful anti-cancer
      therapy. Restoration of wild-type p53 function to cancer cells that have lost it
      might therefore improve treatment outcomes. Using a systematic yeast genetic
      approach, we selected second-site suppressor mutations that can overcome the
      deleterious effects of common p53 cancer mutations in human cells. We identified
      several suppressor mutations for the V143A, G245S and R249S cancer mutations. The
      beneficial effects of these suppressor mutations were demonstrated using
      mammalian reporter gene and apoptosis assays. Further experiments showed that
      these suppressor mutations could override additional p53 cancer mutations. The
      mechanisms of such suppressor mutations can be elucidated by structural studies,
      ultimately leading to a framework for the discovery of small molecules able to
      stabilize p53 mutants.

PMID- 9524110
TI  - Mice deficient for the secreted glycoprotein SPARC/osteonectin/BM40 develop
      normally but show severe age-onset cataract formation and disruption of the lens.
AB  - SPARC (secreted protein acidic and rich in cysteine, also known as
      osteonectin/BM40) is a secreted Ca2+-binding glycoprotein that interacts with a
      range of extracellular matrix molecules, including collagen IV. It is widely
      expressed during embryogenesis, and in vitro studies have suggested roles in the
      regulation of cell adhesion and proliferation, and in the modulation of cytokine
      activity. In order to analyse the function of this protein in vivo, the
      endogenous Sparc locus was disrupted by homologous recombination in murine
      embryonic stem cells. SPARC-deficient mice (Sparctm1Cam) appear normal and
      fertile until around 6 months of age, when they develop severe eye pathology
      characterized by cataract formation and rupture of the lens capsule. The first
      sign of lens pathology occurs in the equatorial bow region where vacuoles
      gradually form within differentiating epithelial cells and fibre cells. The lens
      capsule, however, shows no qualitative changes in the major basal lamina proteins
      laminin, collagen IV, perlecan or entactin. These mice are an excellent resource
      for further studies on how SPARC affects cell behaviour in vivo.

PMID- 9524111
TI  - The CD3gamma chain is essential for development of both the TCRalphabeta and
      TCRgammadelta lineages.
AB  - CD3gamma and CD3delta are the most closely related CD3 components, both of which
      participate in the TCRalphabeta-CD3 complex expressed on mature T cells.
      Interestingly, however, CD3delta does not appear to participate functionally in
      the pre-T-cell receptor (TCR) complex that is expressed on immature T cells:
      disruption of CD3delta gene expression has no effect on the developmental steps
      controlled by the pre-TCR. Here we report that in contrast with CD3delta,
      CD3gamma is an essential component of the pre-TCR. We generated mice selectively
      lacking expression of CD3gamma, in which expression of CD3delta, CD3epsilon,
      CD3zeta, pTalpha and TCRbeta remained undisturbed. Thus, all components for
      composing a pre-TCR are available, with the exception of CD3gamma. Nevertheless,
      T-cell development is severely inhibited in CD3gamma-deficient mice. The number
      of cells in the thymus is reduced to <1% of that in normal mice, and the large
      majority of thymocytes lack CD4 and CD8 and are arrested at the CD44-CD25+ double
      negative (DN) stage of development. Peripheral lymphoid organs are also
      practically devoid of T cells, with absolute numbers of peripheral T cells
      reduced to only 2-5% of those in normal mice. Both TCRalphabeta and TCRgammadelta
      lineages fail to develop effectively in CD3gamma-deficient mice, although absence
      of CD3gamma has no effect on gene rearrangements of the TCRbeta, delta and gamma
      loci. Furthermore, absence of CD3gamma results in a severe reduction in the level
      of TCR and CD3epsilon expression at the cell surface of thymocytes and peripheral
      T cells. The defect in the DN to double positive transition in mice lacking
      CD3gamma can be overcome by anti-CD3epsilon-mediated cross-linking. CD3gamma is
      thus essential for pre-TCR function.

PMID- 9524112
TI  - A distinct 14 residue site triggers coiled-coil formation in cortexillin I.
AB  - We have investigated the process of the assembly of the Dictyostelium discoideum
      cortexillin I oligomerization domain (Ir) into a tightly packed, two-stranded,
      parallel coiled-coil structure using a variety of recombinant polypeptide chain
      fragments. The structures of these Ir fragments were analyzed by circular
      dichroism spectroscopy, analytical ultracentrifugation and electron microscopy.
      Deletion mapping identified a distinct 14 residue site within the Ir coiled coil,
      Arg311-Asp324, which was absolutely necessary for dimer formation, indicating
      that heptad repeats alone are not sufficient for stable coiled-coil formation.
      Moreover, deletion of the six N-terminal heptad repeats of Ir led to the
      formation of a four- rather than a two-helix structure, suggesting that the full
      length cortexillin I coiled-coil domain behaves as a cooperative folding unit.
      Most interestingly, a 16 residue peptide containing the distinct coiled-coil
      'trigger' site Arg311-Asp324 yielded approximately 30% helix formation as
      monomer, in aqueous solution. pH titration and NaCl screening experiments
      revealed that the peptide's helicity depends strongly on pH and ionic strength,
      indicating that electrostatic interactions by charged side chains within the
      peptide are critical in stabilizing its monomer helix. Taken together, these
      findings demonstrate that Arg311-Asp324 behaves as an autonomous helical folding
      unit and that this distinct Ir segment controls the process of coiled-coil
      formation of cortexillin I.

PMID- 9524113
TI  - Phosphorylation of human keratin 18 serine 33 regulates binding to 14-3-3
      proteins.
AB  - Members of the 14-3-3 protein family bind the human intermediate filament protein
      keratin 18 (K18) in vivo, in a cell-cycle- and phosphorylation-dependent manner.
      We identified K18 Ser33 as an interphase phosphorylation site, which increases
      its phosphorylation during mitosis in cultured cells and regenerating liver, and
      as an in vitro cdc2 kinase phosphorylation site. Comparison of wild-type versus
      K18 Ser33-->Ala/Asp transfected cells showed that K18 Ser33 phosphorylation is
      essential for the association of K18 with 14-3-3 proteins, and plays a role in
      keratin organization and distribution. Mutation of another K18 major
      phosphorylation site (Ser52) or K18 glycosylation sites had no effect on the
      binding of K18 to 14-3-3 proteins. The K18 phospho-Ser33 motif is different from
      several 14-3-3-binding phosphomotifs already described. Antibodies that are
      specific to K18 phospho-Ser33 or phospho-Ser52 show that although Ser52 and Ser33
      phosphorylated K18 molecules manifest partial colocalization, these
      phosphorylation events reside predominantly on distinct K18 molecules. Our
      results demonstrate a unique K18 phosphorylation site that is necessary but not
      sufficient for K18 binding to 14-3-3 proteins. This binding is likely to involve
      one or more mitotic events coupled to K18 Ser33 phosphorylation, and plays a role
      in keratin subcellular distribution. Physiological Ser52 or Ser33 phosphorylation
      on distinct K18 molecules suggests functional compartmentalization of these
      modifications.

PMID- 9524114
TI  - TyeA, a protein involved in control of Yop release and in translocation of
      Yersinia Yop effectors.
AB  - Extracellular Yersinia spp. disarm the immune system by injecting the effector
      Yersinia outer proteins (Yops) into the target cell. Yop secretion is triggered
      by contact with eukaryotic cells or by Ca2+ chelation. Two proteins, YopN and
      LcrG, are known to be involved in Yop-secretion control. Here we describe TyeA, a
      third protein involved in the control of Yop release. Like YopN, TyeA is
      localized at the bacterial surface. A tyeA knock-out mutant secreted Yops in the
      presence of Ca2+ and in the absence of eukaryotic cells. Unlike a yopN null
      mutant, the tyeA mutant was defective for translocation of YopE and YopH, but not
      YopM, YopO and YopP, into eukaryotic cells. This is the first observation
      suggesting that Yop effectors can be divided into two sets for delivery into
      eukaryotic cells. TyeA was found to interact with the translocator YopD and with
      residues 242-293 of YopN. In contrast with a yopN null mutant, a yopNDelta248-272
      mutant was also unable to translocate YopE and YopH. Our results suggest that
      TyeA forms part of the translocation-control apparatus together with YopD and
      YopN, and that the interaction of these proteins is required for selective
      translocation of Yops inside eukaryotic cells.

PMID- 9524115
TI  - Carbohydrate-mediated Golgi to cell surface transport and apical targeting of
      membrane proteins.
AB  - Polarized expression of most epithelial plasma membrane proteins is achieved by
      selective transport from the Golgi apparatus or from endosomes to a specific cell
      surface domain. In Madin-Darby canine kidney (MDCK) cells, basolateral sorting
      generally depends on distinct cytoplasmic targeting determinants. Inactivation of
      these signals often resulted in apical expression, suggesting that apical
      transport of transmembrane proteins occurs either by default or is mediated by
      widely distributed characteristics of membrane glycoproteins. We tested the
      hypothesis of N-linked carbohydrates acting as apical targeting signals using
      three different membrane proteins. The first two are normally not glycosylated
      and the third one is a glycoprotein. In all three cases, N-linked carbohydrates
      were clearly able to mediate apical targeting and transport. Cell surface
      transport of proteins containing cytoplasmic basolateral targeting determinants
      was not significantly affected by N-linked sugars. In the absence of
      glycosylation and a basolateral sorting signal, the reporter proteins accumulated
      in the Golgi complex of MDCK as well as CHO cells, indicating that efficient
      transport from the Golgi apparatus to the cell surface is signal-mediated in
      polarized and non-polarized cells.

PMID- 9524116
TI  - Two distinct effectors of the small GTPase Rab5 cooperate in endocytic membrane
      fusion.
AB  - Using the yeast two-hybrid system, we have identified a novel 62 kDa coiled-coil
      protein that specifically interacts with the GTP-bound form of Rab5, a small
      GTPase that regulates membrane traffic in the early endocytic pathway. This
      protein shares 42% sequence identity with Rabaptin-5, a previously identified
      effector of Rab5, and we therefore named it Rabaptin-5beta. Like Rabaptin-5,
      Rabaptin-5beta displays heptad repeats characteristic of coiled-coil proteins and
      is recruited on the endosomal membrane by Rab5 in a GTP-dependent manner.
      However, Rabaptin-5beta has features that distinguish it from Rabaptin-5. The
      relative expression levels of the two proteins varies in different cell types.
      Rabaptin-5beta does not heterodimerize with Rabaptin-5, and forms a distinct
      complex with Rabex-5, the GDP/GTP exchange factor for Rab5. Immunodepletion of
      the Rabaptin-5beta complex from cytosol only partially inhibits early endosome
      fusion in vitro, whereas the additional depletion of the Rabaptin-5 complex has a
      stronger inhibitory effect. Fusion activity can mostly be recovered by addition
      of the Rabaptin-5 complex alone, but maximal fusion efficiency requires the
      presence of both Rabaptin-5 and Rabaptin-5beta complexes. Our results suggest
      that Rab5 binds to at least two distinct effectors which cooperate for optimal
      endocytic membrane docking and fusion.

PMID- 9524117
TI  - Distinct Rab-binding domains mediate the interaction of Rabaptin-5 with GTP-bound
      Rab4 and Rab5.
AB  - Rabaptin-5 functions as an effector for the small GTPase Rab5, a regulator of
      endocytosis and early endosome fusion. We have searched for structural
      determinants that confer functional specificity on Rabaptin-5. Here we report
      that native cytosolic Rabaptin-5 is present in a homodimeric state and
      dimerization depends upon the presence of its coiled-coil predicted sequences. A
      73 residue C-terminal region of Rabaptin-5 is necessary and sufficient both for
      the interaction with Rab5 and for Rab5-dependent recruitment of the protein on
      early endosomes. Surprisingly, we uncovered the presence of an additional Rab
      binding domain at the N-terminus of Rabaptin-5. This domain mediates the direct
      interaction with the GTP-bound form of Rab4, a small GTPase that has been
      implicated in recycling from early endosomes to the cell surface. Based on these
      results, we propose that Rabaptin-5 functions as a molecular linker between two
      sequentially acting GTPases to coordinate endocytic and recycling traffic.

PMID- 9524118
TI  - A cytoplasmic cell cycle controls the activity of a K+ channel in pre
      implantation mouse embryos.
AB  - We previously have reported that the activity of a 240 pS K+ channel varies
      during the cell cycle in pre-implantation mouse embryos. In the present study, we
      show that: (i) the cycling of channel activity is not prevented by inhibiting
      protein synthesis and hence does not involve cyclin-dependent kinase 1 (cdk1)
      cyclin B; and (ii) the cycling of channel activity continues in anucleate zygote
      fragments with a time course similar to that observed in nucleate fragments. We
      further demonstrate that: (i) persistent activation of the K+ channel in one-cell
      embryos arrested in metaphase requires the maintenance of an active cdk1-cyclin B
      complex; and (ii) both DNA synthesis inhibition with aphidicolin and DNA damage
      produced by mitomycin C prevent the down-regulation of the channel at the start
      of S phase by a mechanism that requires tyrosine kinase activation. Thus, the 240
      pS K+ channel in these cells is controlled by a previously unsuspected
      cytoplasmic clock that functions independently of the well-known clock
      controlling the chromosomal cell cycle, but can interact with it.

PMID- 9524119
TI  - Phosphatidylinositol-3,4,5-trisphosphate (PtdIns-3,4,5-P3)/Tec kinase-dependent
      calcium signaling pathway: a target for SHIP-mediated inhibitory signals.
AB  - Tec family non-receptor tyrosine kinases have been implicated in signal
      transduction events initiated by cell surface receptors from a broad range of
      cell types, including an essential role in B-cell development. A unique feature
      of several Tec members among known tyrosine kinases is the presence of an N
      terminal pleckstrin homology (PH) domain. We directly demonstrate that
      phosphatidylinositol-3,4,5-trisphosphate (PtdIns-3,4,5-P3) interacting with the
      PH domain acts as an upstream activation signal for Tec kinases, resulting in Tec
      kinase-dependent phospholipase Cgamma (PLCgamma) tyrosine phosphorylation and
      inositol trisphosphate production. In addition, we show that this pathway is
      blocked when an SH2-containing inositol phosphatase (SHIP)-dependent inhibitory
      receptor is engaged. Together, our results suggest a general mechanism whereby
      PtdIns-3,4,5-P3 regulates receptor-dependent calcium signals through the function
      of Tec kinases.

PMID- 9524120
TI  - Btk/Tec kinases regulate sustained increases in intracellular Ca2+ following B
      cell receptor activation.
AB  - Bruton's tyrosine kinase (Btk) is essential for B-lineage development and
      represents an emerging family of non-receptor tyrosine kinases implicated in
      signal transduction events initiated by a range of cell surface receptors.
      Increased dosage of Btk in normal B cells resulted in a striking enhancement of
      extracellular calcium influx following B-cell antigen receptor (BCR) cross
      linking. Ectopic expression of Btk, or related Btk/Tec family kinases, restored
      deficient extracellular Ca2+ influx in a series of novel Btk-deficient human B
      cell lines. Btk and phospholipase Cgamma (PLCgamma) co-expression resulted in
      tyrosine phosphorylation of PLCgamma and required the same Btk domains as those
      for Btk-dependent calcium influx. Receptor-dependent Btk activation led to
      enhanced peak inositol trisphosphate (IP3) generation and depletion of
      thapsigargin (Tg)-sensitive intracellular calcium stores. These results suggest
      that Btk maintains increased intracellular calcium levels by controlling a Tg
      sensitive, IP3-gated calcium store(s) that regulates store-operated calcium
      entry. Overexpression of dominant-negative Syk dramatically reduced the initial
      phase calcium response, demonstrating that Btk/Tec and Syk family kinases may
      exert distinct effects on calcium signaling. Finally, co-cross-linking of the BCR
      and the inhibitory receptor, FcgammaRIIb1, completely abrogated Btk-dependent IP3
      production and calcium store depletion. Together, these data demonstrate that Btk
      functions at a critical crossroads in the events controlling calcium signaling by
      regulating peak IP3 levels and calcium store depletion.

PMID- 9524121
TI  - Free [Ca2+] dynamics measured in agonist-sensitive stores of single living intact
      cells: a new look at the refilling process.
AB  - Free [Ca2+] in agonist-sensitive internal stores of single intact cells was
      measured in situ in order to examine the role of [Ca2+] in modulating the store
      refilling process. BHK-21 fibroblasts were loaded with the low-affinity
      fluorescent calcium indicator mag-fura-2-AM such that >80% of the dye was trapped
      in organelles, where it reported [Ca2+] changes solely in an agonist- and
      thapsigargin-sensitive internal store. The rates of store reloading following
      stimulation by 100 nM bradykinin were essentially unchanged when cytosolic [Ca2+]
      was clamped to resting values with BAPTA-AM. In control cells, recharging of
      stores totally depended on the presence of external Ca2+, but pre-loading the
      cells with BAPTA-AM permitted efficient refilling in Ca2+-free, EGTA-containing
      external medium. Our results show: (i) Ca2+ stores normally are recharged by Ca2+
      which must first transit the cytoplasm; (ii) an elevation in cytoplasmic [Ca2+]
      is not required to replenish Ca2+ stores; (iii) the activation of the plasma
      membrane Ca2+ pump during the Ca2+ spike ordinarily results in complete extrusion
      of released Ca2+; and (iv) the buffering capacity of the cytoplasm is an
      essential component of the store refilling process. An interesting finding was
      that acute treatment of cells with BAPTA-AM activated capacitative Ca2+ entry at
      the plasma membrane, due to its efficient hydrolysis in the stores, and the
      ensuing decrease in the endoplasmic reticulum [Ca2+].

PMID- 9524122
TI  - GPR1 encodes a putative G protein-coupled receptor that associates with the Gpa2p
      Galpha subunit and functions in a Ras-independent pathway.
AB  - The yeast RAS1 and RAS2 genes appear to be involved in control of cell growth in
      response to nutrients. Here we show that this growth control also involves a
      signal mediated by the heterotrimeric G protein alpha subunit homolog encoded by
      GPA2. A GPA2 null allele conferred a severe growth defect on cells containing a
      null allele of RAS2, although either mutation alone had little effect on growth
      rate. A constitutive allele of GPA2 could stimulate growth of a strain lacking
      both RAS genes. Constitutive GPA2 conferred heat shock sensitivity on both wild
      type cells and cells lacking RAS function, but had no effect in a strain
      containing a null allele of SCH9, which encodes a kinase related to protein
      kinase A. The GPR1 gene was isolated and was found to encode a protein with the
      characteristics of a G protein-coupled receptor. Double Deltagpr1 Deltaras2
      mutants displayed a severe growth defect that was suppressed by expression of the
      constitutive allele of GPA2, confirming that GPR1 acts upstream of GPA2. Gpr1p is
      expressed on the cell surface and requires sequences in the membrane-proximal
      region of its third cytoplasmic loop for function, as expected for a G protein
      coupled receptor. GPR1 RNA was induced when cells were starved for nitrogen and
      amino acids. These results are consistent with a model in which the GPR1/GPA2
      pathway activates the Sch9p kinase to generate a response that acts in parallel
      with that generated by the Ras/cAMP pathway, resulting in the integration of
      nutrient signals.

PMID- 9524123
TI  - Activation of the Src/p21ras/Erk pathway by progesterone receptor via cross-talk
      with estrogen receptor.
AB  - The molecular mechanisms by which ovarian hormones stimulate growth of breast
      tumors are unclear. It has been reported previously that estrogens activate the
      signal-transducing Src/p21(ras)/Erk pathway in human breast cancer cells via an
      interaction of estrogen receptor (ER) with c-Src. We now show that progestins
      stimulate human breast cancer T47D cell proliferation and induce a similar rapid
      and transient activation of the pathway which, surprisingly, is blocked not only
      by anti-progestins but also by anti-estrogens. In Cos-7 cells transfected with
      the B isoform of progesterone receptor (PRB), progestin activation of the MAP
      kinase pathway depends on co-transfection of ER. A transcriptionally inactive PRB
      mutant also activates the signaling pathway, demonstrating that this activity is
      independent of transcriptional effects. PRB does not interact with c-Src but
      associates via the N-terminal 168 amino acids with ER. This association is
      required for the signaling pathway activation by progestins. We propose that ER
      transmits to the Src/p21(ras)/Erk pathway signals received from the agonist
      activated PRB. These findings reveal a hitherto unrecognized cross-talk between
      ovarian hormones which could be crucial for their growth-promoting effects on
      cancer cells.

PMID- 9524124
TI  - UTF1, a novel transcriptional coactivator expressed in pluripotent embryonic stem
      cells and extra-embryonic cells.
AB  - We have obtained a novel transcriptional cofactor, termed undifferentiated
      embryonic cell transcription factor 1 (UTF1), from F9 embryonic carcinoma (EC)
      cells. This protein is expressed in EC and embryonic stem cells, as well as in
      germ line tissues, but could not be detected in any of the other adult mouse
      tissues tested. Furthermore, when EC cells are induced to differentiate, UTF1
      expression is rapidly extinguished. In normal mouse embryos, UTF1 mRNA is present
      in the inner cell mass, the primitive ectoderm and the extra-embryonic tissues.
      During the primitive streak stage, the induction of mesodermal cells is
      accompanied by the down-regulation of UTF1 in the primitive ectoderm. However,
      its expression is maintained for up to 13.5 days post-coitum in the extra
      embryonic tissue. Functionally, UTF1 boosts the level of transcription of the
      adenovirus E2A promoter. However, unlike the pluripotent cell-specific E1A-like
      activity, which requires the E2F sites of the E2A promoter for increased
      transcriptional activation, UTF1-mediated activation is dependent on the upstream
      ATF site of this promoter. This result indicates that UTF1 is not a major
      component of the E1A-like activity present in pluripotent embryonic cells.
      Further analyses revealed that UTF1 interacts not only with the activation domain
      of ATF-2, but also with the TFIID complex in vivo. Thus, UTF1 displays many of
      the hallmark characteristics expected for a tissue-specific transcriptional
      coactivator that works in early embryogenesis.

PMID- 9524125
TI  - Efficient synthesis, termination and release of RNA polymerase III transcripts in
      Xenopus extracts depleted of La protein.
AB  - La proteins are conserved, abundant and predominantly nuclear phosphoproteins
      which bind to the 3'-U termini of newly synthesized RNA polymerase III
      transcripts. The human La protein has been implicated in the synthesis,
      termination and release of such transcripts. Here we examine the potential
      transcriptional properties of La in Xenopus laevis, using a homologous tRNA gene
      as template. Immunodepletion of La from cell-free extracts leads to the formation
      of tRNA precursors lacking 3'-U residues. This shortening can be uncoupled from
      RNA polymerase III transcription, indicating that it results from nuclease
      degradation rather than incomplete synthesis. Extracts containing <1% of the
      normal La protein content synthesize tRNA precursors just as well as complete
      extracts, with no change in termination efficiency, and the vast majority of
      these full-length transcripts are not associated with the template or with
      residual La protein. Hence, Xenopus La seems not to function as an initiation,
      termination or release factor for RNA polymerase III. Consistent with the
      recently discovered role of La in yeast tRNA maturation in vivo, recombinant
      Xenopus La prevents 3'-exonucleolytic degradation of tRNA precursors in vitro. A
      conserved RNA chaperone function may best explain the abundance of La in
      eukaryotic nuclei.

PMID- 9524126
TI  - FacB, the Aspergillus nidulans activator of acetate utilization genes, binds
      dissimilar DNA sequences.
AB  - The facB gene is required for acetate induction of acetamidase (amdS) and the
      acetate utilization enzymes acetyl-CoA synthase (facA), isocitrate lyase (acuD)
      and malate synthase (acuE) in Aspergillus nidulans. The facB gene encodes a
      transcriptional activator with a GAL4-type Zn(II)2Cys6 zinc binuclear cluster DNA
      binding domain which is shown to be required for DNA binding. In vitro DNA
      binding sites for FacB in the 5' regions of the amdS, facA, acuD and acuE genes
      have been identified. Mutations in amdS FacB DNA-binding sites affected
      expression of an amdS-lacZ reporter in vivo and altered the affinity of in vitro
      DNA binding. This study shows that the FacB Zn(II)2Cys6 cluster binds to
      dissimilar sites which show similarity in form but not sequence with DNA-binding
      sites of other Zn(II)2Cys6 proteins. Sequences with homology to FacB sites are
      found in the 5' regions of genes regulated by the closely related yeast
      Zn(II)2Cys6 protein CAT8.

PMID- 9524127
TI  - Hus1p, a conserved fission yeast checkpoint protein, interacts with Rad1p and is
      phosphorylated in response to DNA damage.
AB  - The hus1+ gene is one of six fission yeast genes, termed the checkpoint rad
      genes, which are essential for both the S-M and DNA damage checkpoints. Classical
      genetics suggests that these genes are required for activation of the PI-3 kinase
      related (PIK-R) protein, Rad3p. Using a dominant negative allele of hus1+, we
      have demonstrated a genetic interaction between hus1+ and another checkpoint rad
      gene, rad1+. Hus1p and Rad1p form a stable complex in wild-type fission yeast,
      and the formation of this complex is dependent on a third checkpoint rad gene,
      rad9+, suggesting that these three proteins may exist in a discrete complex in
      the absence of checkpoint activation. Hus1p is phosphorylated in response to DNA
      damage, and this requires rad3+ and each of the other checkpoint rad genes.
      Although there is no gene related to hus1+ in the Saccharomyces cerevisiae
      genome, we have identified closely related mouse and human genes, suggesting that
      aspects of the checkpoint control mechanism are conserved between fission yeast
      and higher eukaryotes.

PMID- 9524129
TI  - In vivo analysis of scaffold-associated regions in Drosophila: a synthetic high
      affinity SAR binding protein suppresses position effect variegation.
AB  - Scaffold-associated regions (SARs) were studied in Drosophila melanogaster by
      expressing a synthetic, high-affinity SAR-binding protein called MATH (multi-AT
      hook), which consists of reiterated AT-hook peptide motifs; each motif is known
      to recognize a wide variety of short AT-rich sequences. MATH proteins were
      expressed specifically in the larval eye imaginal discs by means of the
      tetracycline-regulated transactivation system and tested for their effect on
      position effect variegation (PEV). MATH20, a highly potent SAR ligand consisting
      of 20 AT-hooks, was found to suppress whitemottled 4 variegation. This
      suppression required MATH20 expression at an early larval developmental stage.
      Our data suggest an involvement of the high AT-rich SARs in higher order
      chromatin structure and gene expression.

PMID- 9524128
TI  - Drosophila CtBP: a Hairy-interacting protein required for embryonic segmentation
      and hairy-mediated transcriptional repression.
AB  - hairy is a Drosophila pair-rule segmentation gene that functions genetically as a
      repressor. To isolate protein components of Hairy-mediated repression, we used a
      yeast interaction screen and identified a Hairy-interacting protein, the
      Drosophila homolog of the human C-terminal-binding protein (CtBP). Human CtBP is
      a cellular phosphoprotein that interacts with the C-terminus of the adenovirus
      E1a oncoprotein and functions as a tumor suppressor. dCtBP also interacts with
      E1a in a directed yeast two-hybrid assay. We show that dCtBP interacts
      specifically and directly with a small, previously uncharacterized C-terminal
      region of Hairy. dCtBP activity appears to be specific to Hairy of the
      Hairy/Enhancer of split [E(spl)]/Dpn basic helix-loop-helix protein class. We
      identified a P-element insertion within the dCtBP transcription unit that fails
      to complement alleles of a known locus, l(3)87De. We demonstrate that dCtBP is
      essential for proper embryonic segmentation by analyzing embryos lacking maternal
      dCtBP activity. While Hairy is probably not the only segmentation gene
      interacting with dCtBP, we show dose-sensitive genetic interactions between dCtBP
      and hairy mutations.

PMID- 9524130
TI  - Prp22, a DExH-box RNA helicase, plays two distinct roles in yeast pre-mRNA
      splicing.
AB  - In order to assess the role of Prp22 in yeast pre-mRNA splicing, we have purified
      the 130 kDa Prp22 protein and developed an in vitro depletion/reconstitution
      assay. We show that Prp22 is required for the second step of actin pre-mRNA
      splicing. Prp22 can act on pre-assembled spliceosomes that are arrested after
      step 1 in an ATP-independent fashion. The requirement for Prp22 during step 2
      depends on the distance between the branchpoint and the 3' splice site,
      suggesting a previously unrecognized role for Prp22 in splice site selection. We
      characterize the biochemical activities of Prp22, a member of the DExH-box family
      of proteins, and we show that purified recombinant Prp22 protein is an RNA
      dependent ATPase and an ATP-dependent RNA helicase. Prp22 uses the energy of ATP
      hydrolysis to effect the release of mRNA from the spliceosome. Thus, Prp22 has
      two distinct functions in yeast pre-mRNA splicing: an ATP-independent role during
      the second catalytic step and an ATP-requiring function in disassembly of the
      spliceosome.

PMID- 9524131
TI  - Human homologs of yeast prp16 and prp17 reveal conservation of the mechanism for
      catalytic step II of pre-mRNA splicing.
AB  - Pre-mRNA splicing takes place in two catalytic steps. The second step is poorly
      understood, especially in mammals. In yeast, the splicing factors, Prps 16, 17,
      18 and Slu7 function exclusively in step II. Here we report the isolation of
      cDNAs encoding human Prps 16 and 17 which are 41 and 36% identical to their yeast
      counterparts. The Prp16 gene is essential in yeast, and we show that a chimeric
      yeast-human Prp16 protein rescues a yeast Prp16 knockout strain. Immunodepletion
      of hPrp16 from splicing extracts specifically blocks step II, and the activity
      can be fully restored with recombinant hPrp16. Moreover, both hPrps 16 and 17
      associate with the spliceosome late in the splicing pathway. Mutations at the 3'
      splice site that specifically block step II do not affect the association of
      hPrps 16 and 17 with the spliceosome, indicating that these factors may function
      at a stage of step II prior to recognition of the 3' splice site. Recently, the
      human homologs of Prp18 and Slu7 were identified. The observation that humans
      contain homologs of all four known step II proteins in yeast indicates that the
      mechanism for catalytic step II is highly conserved.

PMID- 9524132
TI  - Nuclear history of a pre-mRNA determines the translational activity of
      cytoplasmic mRNA.
AB  - The pathways of synthesis and maturation of pre-messenger RNA in the nucleus have
      a direct effect on the translational efficiency of mRNA in the cytoplasm. The
      transcription of intron-less mRNA in vivo directs this mRNA towards translational
      silencing. The presence of an intron at the 5' end of the transcript relieves
      this silencing, whereas an intron at the 3' end further represses translation.
      These regulatory events are strongly dependent on the transcription of pre-mRNA
      in the nucleus. The impact of nuclear history on regulatory events in the
      cytoplasm provides a novel mechanism for the control of gene expression.

PMID- 9524133
TI  - Transposase makes critical contacts with, and is stimulated by, single-stranded
      DNA at the P element termini in vitro.
AB  - P elements transpose by a cut-and-paste mechanism. Donor DNA cleavage mediated by
      transposase generates 17 nucleotide (nt) 3' single-strand extensions at the P
      element termini which, when present on oligonucleotide substrates, stimulate both
      the strand-transfer and disintegration reactions in vitro. A significant amount
      of the strand-transfer products are the result of double-ended integration.
      Chemical DNA modification-interference experiments indicate that during the
      strand-transfer reaction, P element transposase contacts regions of the substrate
      DNA that include the transposase binding site and the duplex portion of the 31 bp
      inverted repeat, as well as regions of the terminal 17 nt single-stranded DNA.
      Together these data suggest that the P element transposase protein contains two
      DNA-binding sites and that the active oligomeric form of the transposase protein
      is at least a dimer.

PMID- 9524135
TI  - Steady state relation between cytoplasmic free Ca2+ concentration and force in
      intact frog skeletal muscle fibers.
AB  - The steady state relation between cytoplasmic Ca2+ concentration ([Ca2+]i) and
      force was studied in intact skeletal muscle fibers of frogs. Intact twitch fibers
      were injected with the dextran-conjugated Ca2+ indicator, fura dextran, and the
      fluorescence signals of fura dextran were converted to [Ca2+]i using calibration
      parameters previously estimated in permeabilized muscle fibers (Konishi and
      Watanabe. 1995. J. Gen. Physiol. 106:1123-1150). In the first series of
      experiments, [Ca2+]i and isometric force were simultaneously measured during high
      K+ depolarization. Slow changes in [Ca2+]i and force induced by 15-30 mM K+
      appeared to be in equilibrium, as instantaneous [Ca2+]i versus force plot tracked
      the common path in the rising and relaxation phases of K+ contractures. In the
      second series of experiments, 2,5-di-tert-butylhydroquinone (TBQ), an inhibitor
      of the sarcoplasmic reticulum Ca2+ pump, was used to decrease the rate of decline
      of [Ca2+]i after tetanic stimulation. The decay time courses of both [Ca2+]i and
      force were dose-dependently slowed by TBQ up to 5 micro M; the instantaneous
      [Ca2+]i- force relations were nearly identical at >/=1 micro M TBQ, suggesting
      that the change in [Ca2+]i was slow enough to reach equilibrium with force. The
      [Ca2+]i-force data obtained from the two types of experiments were consistent
      with the Hill curve using a Hill coefficient of 3.2-3.9 and [Ca2+]i for half
      activation (Ca50) of 1.5-1.7 micro M. However, if fura dextran reacts with Ca2+
      with a 2.5-fold greater Kd as previously estimated from the kinetic fitting
      (Konishi and Watanabe. 1995. J. Gen. Physiol. 106:1123-1150), Ca50 would be 3.7
      4.2 micro M. We also studied the [Ca2+]-force relation in skinned fibers under
      similar experimental conditions. The average Hill coefficient and Ca50 were
      estimated to be 3.3 and 1.8 microM, respectively. Although uncertainties remain
      about the precise levels of [Ca2+]i, we conclude that the steady state force is a
      3rd to 4th power function of [Ca2+]i, and Ca50 is in the low micromolar range in
      intact frog muscle fibers, which is in reasonable agreement with results obtained
      from skinned fibers.

PMID- 9524134
TI  - Control of maximum sarcoplasmic reticulum Ca load in intact ferret ventricular
      myocytes. Effects Of thapsigargin and isoproterenol.
AB  - In steady state, the Ca content of the sarcoplasmic reticulum (SR) of cardiac
      myocytes is determined by a balance among influx and efflux pathways. The SR Ca
      content may be limited mainly by the ATP-supplied chemical potential that is
      inherent in the gradient between SR and cytosol. That is, forward Ca pumping from
      cytosol to SR may be opposed by energetically conservative reverse pumping
      dependent on intra-SR free [Ca]. On the other hand, SR Ca loading may be limited
      by dissipative pathways (pump slippage and/or pump-independent leak). To assess
      how SR Ca content is limited, we loaded voltage-clamped ferret ventricular
      myocytes cumulatively with known amounts of Ca via L-type Ca channels (ICa),
      using Na-free solutions to prevent Na/Ca exchange. We then measured the maximal
      resulting caffeine-released SR Ca content under control conditions, as well as
      when SR Ca pumping was accelerated by isoproterenol (1 micro M) or slowed by
      thapsigargin (0.2-0.4 micro M). Under control conditions, SR Ca content reached a
      limit of 137 micro mol.liter cytosol-1 (nonmitochondrial volume) when measured by
      integrating caffeine-induced Na/Ca exchange currents lintegraINaCaXdt) and of 119
      micro mol.liter cytosol-1 when measured using fluorescence signals dependent on
      changes in cytosolic free Ca ([Ca]i). When Ca-ATPase pumping rate was slowed 39%
      by thapsigargin, the maximal SR Ca content decreased by 5 (integralINaCaXdt
      method) or 23% (fluorescence method); when pumping rate was increased 74% by
      isoproterenol, SR Ca content increased by 10% (fluorescence method) or 20%
      (integralINaCaXdt method). The relative stability of the SR Ca load suggests that
      dissipative losses have only a minor influence in setting the SR Ca content.
      Indeed, it appears that the SR Ca pump in intact cells can generate a [Ca]
      gradient approaching the thermodynamic limit.

PMID- 9524136
TI  - Monovalent permeability, rectification, and ionic block of store-operated calcium
      channels in Jurkat T lymphocytes.
AB  - We used whole-cell recording to characterize ion permeation, rectification, and
      block of monovalent current through calcium release-activated calcium (CRAC)
      channels in Jurkat T lymphocytes. Under physiological conditions, CRAC channels
      exhibit a high degree of selectivity for Ca2+, but can be induced to carry a
      slowly declining Na+ current when external divalent ions are reduced to
      micromolar levels. Using a series of organic cations as probes of varying size,
      we measured reversal potentials and calculated permeability ratios relative to
      Na+, PX/PNa, in order to estimate the diameter of the conducting pore. Ammonium
      (NH4+) exhibited the highest relative permeability (PNH4/PNa = 1.37). The largest
      permeant ion, tetramethylammonium with a diameter of 0.55 nm, had PTMA/PNa of
      0.09. N-methyl-D-glucamine (0.50 x 0.64 x 1.20 nm) was not measurably permeant.
      In addition to carrying monovalent current, NH4+ reduced the slow decline of
      monovalent current ("inactivation") upon lowering [Ca2+]o. This kinetic effect of
      extracellular NH4+ can be accounted for by an increase in intracellular pH (pHi),
      since raising intracellular pH above 8 reduced the extent of inactivation. In
      addition, decreasing pHi reduced monovalent and divalent current amplitudes
      through CRAC channels with a pKa of 6.8. In several channel types, Mg2+ has been
      shown to produce rectification by a voltage-dependent block mechanism. Mg2+
      removal from the pipette solution permitted large outward monovalent currents to
      flow through CRAC channels while also increasing the channel's relative Cs+
      conductance and eliminating the inactivation of monovalent current. Boltzmann
      fits indicate that intracellular Mg2+ contributes to inward rectification by
      blocking in a voltage-dependent manner, with a z delta product of 1.88. Ca2+
      block from the outside was also found to be voltage dependent with z delta of
      1.62. These experiments indicate that the CRAC channel, like voltage-gated Ca2+
      channels, achieves selectivity for Ca2+ by selective binding in a large pore with
      current-voltage characteristics shaped by internal Mg2+.

PMID- 9524137
TI  - On the mechanism by which 4-Aminopyridine occludes quinidine block of the cardiac
      K+ channel, hKv1.5.
AB  - 4-Aminopyridine (4-AP) binds to potassium channels at a site or sites in the
      inner mouth of the pore and is thought to prevent channel opening. The return of
      hKv1.5 off-gating charge upon repolarization is accelerated by 4-AP and it has
      been suggested that 4-AP blocks slow conformational rearrangements during late
      closed states that are necessary for channel opening. On the other hand,
      quinidine, an open channel blocker, slows the return or immobilizes off-gating
      charge only at opening potentials (>-25 mV). The aim of this study was to use
      quinidine as a probe of open channels to test the kinetic state of 4-AP-blocked
      channels. In the presence of 0.2-1 mM 4-AP, quinidine slowed charge return and
      caused partial charge immobilization, corresponding to an increase in the Kd of
      approximately 20-fold. Peak off-gating currents were reduced and decay was slowed
      approximately 2- to 2.5-fold at potentials negative to the threshold of channel
      activation and during depolarizations shorter than normally required for channel
      activation. This demonstrated access of quinidine to 4-AP-blocked channels, a
      lack of competition between the two drugs, and implied allosteric modulation of
      the quinidine binding site by 4-AP resident within the channel. Single channel
      recordings also showed that quinidine could modulate the 4-AP-induced closure of
      the channels, with the result that frequent channel reopenings were observed when
      both drugs were present. We propose that 4-AP-blocked channels exist in a
      partially open, nonconducting state that allows access to quinidine, even at more
      negative potentials and during shorter depolarizations than those required for
      channel activation.

PMID- 9524138
TI  - Specific antibodies to the external vestibule of voltage-gated potassium channels
      block current.
AB  - Using delayed-rectifier potassium channels as examples, we have designed two
      specific blockers by generating specific antipeptide antibodies to epitopes in
      the external vestibules of two channel proteins, Kv1.2 and Kv3.1. These
      antibodies reduced whole-cell Kv1.2 or Kv3.1 currents in transfected cells and
      the effect was blocked by the corresponding peptide antigen, but not by control
      peptides. A control antibody had little effect on Kv1.2 currents and the Kv1.2
      blocker antibody had limited effect on other related potassium currents.
      Furthermore, the Kv1.2 blocking antibody inhibited dendrotoxin binding to Kv1.2
      channel proteins in transfected cells. Moreover, using the Kv1.2 blocker
      antibody, we determined the presence and relative contribution of endogenous
      Kv1.2 to the overall endogenous K+ currents in NG108 neuronal cells. This guided
      design of specific channel blockers will facilitate future physiological studies
      on ion channel functions.

PMID- 9524139
TI  - Gating of recombinant small-conductance Ca-activated K+ channels by calcium.
AB  - Small-conductance Ca-activated K+ channels play an important role in modulating
      excitability in many cell types. These channels are activated by submicromolar
      concentrations of intracellular Ca2+, but little is known about the gating
      kinetics upon activation by Ca2+. In this study, single channel currents were
      recorded from Xenopus oocytes expressing the apamin-sensitive clone rSK2. Channel
      activity was detectable in 0.2 micro M Ca2+ and was maximal above 2 micro M Ca2+.
      Analysis of stationary currents revealed two open times and three closed times,
      with only the longest closed time being Ca dependent, decreasing with increasing
      Ca2+ concentrations. In addition, elevated Ca2+ concentrations resulted in a
      larger percentage of long openings and short closures. Membrane voltage did not
      have significant effects on either open or closed times. The open probability was
      approximately 0.6 in 1 micro M free Ca2+. A lower open probability of
      approximately 0.05 in 1 micro M Ca2+ was also observed, and channels switched
      spontaneously between behaviors. The occurrence of these switches and the amount
      of time channels spent displaying high open probability behavior was Ca2+
      dependent. The two behaviors shared many features including the open times and
      the short and intermediate closed times, but the low open probability behavior
      was characterized by a different, long Ca2+-dependent closed time in the range of
      hundreds of milliseconds to seconds. Small-conductance Ca- activated K+ channel
      gating was modeled by a gating scheme consisting of four closed and two open
      states. This model yielded a close representation of the single channel data and
      predicted a macroscopic activation time course similar to that observed upon fast
      application of Ca2+ to excised inside-out patches.

PMID- 9524142
TI  - Exploring Spatial Resolution in Electron Back-Scattered Diffraction Experiments
      via Monte Carlo Simulation
AB  - A Monte Carlo model was used to simulate specimen-electron beam interactions
      relevant to electron back-scattered diffraction (EBSD). Electron trajectories
      were calculated for a variety of likely experimental conditions to examine the
      interaction volume of the incident electrons as well as that of the subset of
      incident electrons that emerge from the specimen, i.e., back-scattered electrons
      (BSEs). The spatial resolution of EBSD was investigated as functions of both
      materials properties, such as atomic number, atomic weight, and density, and
      experimental parameters, such as specimen thickness, tilt, and incident beam
      accelerating voltage. These simulations reveal that the achievable spatial
      resolution in EBSD is determined by these intrinsic and extrinsic parameters.

PMID- 9524143
TI  - Minimizing Transmission Electron Microscopy Beam Damage during the Study of
      Surface Reactions on Sodium Chloride
AB  - : Electron beam damage is a significant limitation for transmission electron
      microscopy (TEM) studies of beam-sensitive samples. An approach for studying
      surface reactions on alkali halide crystals using 200 kV TEM is presented.
      Experiments were designed to monitor the reaction of NaCl crystals with HNO3 gas
      followed by water vapor to form solid NaNO3. During beam damage experiments, TEM
      micrographs record structural changes to both NaCl and NaNO3, including
      dislocation loops, void formation, and decomposition. Sample decomposition can be
      successfully minimized by a combination of commonly used techniques: (1) focusing
      the beam adjacent to the area of interest, (2) lowering the electron density, (3)
      choosing to image larger (micrometer- versus submicrometer-sized) alkali halide
      crystals, and (4) lowering temperature by the use of a liquid nitrogen cooling
      stage. From these results, additional studies were designed that monitored
      sequential experiments. Sensitive micrometer-sized sodium chloride single
      crystals before and after exposure to nitric acid vapor and water vapor and the
      subsequent growth of submicrometer-sized sodium nitrate single crystals could
      then be successfully imaged using TEM.

PMID- 9524140
TI  - Characterization of ether-a-go-go channels present in photoreceptors reveals
      similarity to IKx, a K+ current in rod inner segments.
AB  - In this study, we describe two splice variants of an ether-a-go-go (EAG) K+
      channel cloned from bovine retina: bEAG1 and bEAG2. The bEAG2 polypeptide
      contains an additional insertion of 27 amino acids in the extracellular linker
      between transmembrane segments S3 and S4. The heterologously expressed splice
      variants differ in their activation kinetics and are differently modulated by
      extracellular Mg2+. Cooperativity of modulation by Mg2+ suggests that each
      subunit of the putative tetrameric channel binds a Mg2+ ion. The channels are
      neither permeable to Ca2+ ions nor modulated by cyclic nucleotides. In situ
      hybridization localizes channel transcripts to photoreceptors and retinal
      ganglion cells. Comparison of EAG currents with IKx, a noninactivating K+ current
      in the inner segment of rod photoreceptors, reveals an intriguing similarity,
      suggesting that EAG polypeptides are involved in the formation of Kx channels.

PMID- 9524141
TI  - Adenosine triphosphate-dependent asymmetry of anion permeation in the cystic
      fibrosis transmembrane conductance regulator chloride channel.
AB  - The cystic fibrosis transmembrane conductance regulator (CFTR) forms a tightly
      regulated channel that mediates the passive diffusion of Cl- ions. Here we show,
      using macroscopic current recording from excised membrane patches, that CFTR also
      shows significant, but highly asymmetrical, permeability to a broad range of
      large organic anions. Thus, all large organic anions tested were permeant when
      present in the intracellular solution under biionic conditions (PX/PCl = 0.048
      0.25), whereas most were not measurably permeant when present in the
      extracellular solution. This asymmetry was not observed for smaller anions.
      ATPase inhibitors that "lock" CFTR channels in the open state (pyrophosphate, 5'
      adenylylimidodiphosphate) disrupted the asymmetry of large anion permeation by
      allowing their influx from the extracellular solution, which suggests that ATP
      hydrolysis is required to maintain asymmetric permeability. The ability of CFTR
      to allow efflux of large organic anions represents a novel function of CFTR. Loss
      of this function may contribute to the pleiotropic symptoms seen in cystic
      fibrosis.

PMID- 9524144
TI  - Lenses for Electron Microscopy and Microanalysis: Shadowgraph Method of
      Determining Focal Properties and Aberration Coefficients
AB  - : The performance characteristics of electron microscopes and probe-forming
      instruments depend ultimately on the focal properties and aberrations of electron
      lenses. A practical method of experimentally determining the properties of
      electron lenses is described. The method utilizes shadows cast by two meshes
      inserted separately in front of the lens and behind the lens to study the
      properties of the image of a point source. The image properties are then used to
      calculate the lens properties. The paraxial values of the focal length and focal
      distance as well as their spherical and chromatic aberrations are determined.
      Experimental data and the analysis are presented in the form of a tutorial that
      has been tested in the classroom. Discussions of the relationship between image
      properties and lens properties, in particular, focal point aberrations and focal
      length aberrations, and the various ways aberration coefficients can be defined,
      are included to clarify concepts in optics that are important for microscopists.

PMID- 9524145
TI  - Application of Light Microscopy to Direct Coal Liquefaction Research
AB  - : Light microscopy was used to analyze the effects of added catalyst at different
      conditions (temperature and reaction times) in liquefaction testing of a low
      pyritic sulfur bituminous coal. Quantitative changes in vitrinite/vitroplast
      reflectance of coal and liquefaction residues were shown to be useful markers in
      analyzing and understanding the role of catalyst during the initial stage of coal
      particle hydrogenation. Lower reflectance values corresponded to increased
      conversions up to about the 60 min and 375 degreesC experimental conditions.
      Microscopical observation of liquefaction residues also revealed the presence of
      "wall scales" of varying width.

PMID- 9524146
TI  - Experimental System for X-ray Cone-Beam Microtomography
AB  - : A laboratory test of X-ray tomography employing a diverging beam of X-rays
      rather than the usual parallel X-ray beam is described. We chose to test and
      demonstrate the advantages of divergent beam tomography by imaging an extracted
      juvenile human premolar using an ordinary dental X-ray source and a cooled CCD
      camera. Experiments with a three-piece cover-glass sample and with the human
      tooth demonstrated that three-dimensional reconstruction can be achieved at 34 um
      per pixel resolution employing an X-ray tube spot 800 um in its smallest
      direction without requiring close contact with the fluorescent screen.
      Reconstruction of a 256 x 256 pixel single-plane image from 100 projection images
      took only 45 sec on a personal computer with a Pentium 166 MHz processor. We have
      also demonstrated a volume reconstruction of 256 x 256 x 256 voxels from the
      data. Successful extension of this work to submicrometer projection X-ray
      microscopy is predicted. Improved resolution of medical tomography is another
      possible application.

PMID- 9524148
TI  - Simple and Inexpensive Identification of Film Negatives Used in Light Microscopy
AB  - : We describe here a simple and inexpensive solution for marking film negatives
      with identification numbers before film development. This technique avoids the
      purchase of expensive camera-magazines with data-backs, and it reduces the risk
      of misidentifying film negatives.

PMID- 9524147
TI  - Image Formation in Femtosecond Confocal Interference Microscopy
AB  - : Three-dimensional image formation in an interference confocal scanning
      microscope under ultrashort pulsed beam illumination is investigated in this
      study. The novelty of this new image system is that it keeps advantages in
      femtosecond interferometry but also provides a femtosecond-resolved three
      dimensional image without necessarily using an ultrafast detector. For a 5-fs
      pulsed beam illumination, spatial resolution in the axial and transverse
      directions in this system is improved by approximately 45% and 15%, respectively,
      compared with that in the case of continuous wave illumination. However, strong
      chromatic aberration caused by an ultrashort pulsed beam can result in a
      degradation of spatial and temporal resolution, whereas weak chromatic aberration
      may lead to an improvement in transverse resolution.

PMID- 9524149
TI  - News and Commentary

PMID- 9524150
TI  - Fetal Heart Rate Observations in 300 Term Brain-damaged Infants
AB  - >Objective: To describe the fetal heart rate (FHR) patterns of 300 term brain
      damaged infants.Methods: The fetal monitor strips of 300 singleton term
      neurologically impaired neonates were retrospectively analyzed.Results: Of the
      300 infants, the admission FHR patterns were: reactive, 152 (51%); nonreactive,
      135 (45%); bradycardia, 9 (3%); or unclassifiable, 4 (1%). In the reactive group,
      the FHR did the following: 1) remained reactive throughout labor [24 (16%)]; 2)
      developed an elevated baseline FHR in association with repetitive FHR
      decelerations and, in most instances, a loss of variability [67 (22%)]; or 3)
      developed a sudden prolonged FHR deceleration that lasted until delivery [61
      (20%)]. Finally, the nonreactive admission group exhibited the following: 1) a
      persistent fixed baseline rate from admission (149 +/- 16 beats/min) [97 (72%)];
      2) a prolonged FHR deceleration that lasted until delivery [12 (9%)]; or 3) a
      stair steps to death pattern [26 (19%)].Conclusions: While term infants later
      found to be neurologically impaired do not manifest a uniform FHR pattern, these
      fetuses do manifest distinct FHR patterns intrapartum that can be easily
      categorized and identified on the basis of the fetal admission test and
      subsequent changes in the baseline heart rate. This distinction should prove
      helpful in the management of obstetrical patients in labor.

PMID- 9524151
TI  - Renal Hemodynamics: Longitudinal Study from the Late Fetal Life to One Year of
      Age
AB  - >Objective: To evaluate longitudinally the renal circulation from late gestation
      to the first year of life in order to understand fundamental changes within this
      vascular bed as the fetus adapts to major circulatory changes occurring during
      this time period.Methods: Sixteen healthy human fetuses were studied during the
      last trimester of the pregnancy, within 2 days of birth, at 6 weeks, at 6 months,
      and at 1 year. Using noninvasive color pulsed Doppler, blood flow velocities of
      the renal artery, the tricuspid and mitral valves in the fetus, and in the
      ascending aorta in the newborn/infants were obtained at each study. Diameters of
      these respective areas were also obtained. Total cardiac output and renal blood
      flow were calculated using the time velocity integral, the area of the structure
      of interest, and heart rate.Results: 1) Renal artery dimensions, time velocity
      integral, peak flow velocity, systolic to diastolic ratio, absolute volume blood
      flow (RVBF) were all significantly correlated with advancing gestational age; 2)
      RVBF relative to body weight and percent RVBF were not.Conclusions: In spite of
      an overall increase in renal blood flow, flow to the kidney appears to be
      constant during the time period of this study. Most of the "maturational" changes
      that occur within this vascular bed appear to be related to changes within the
      vascular resistance and the renal artery diameter.

PMID- 9524152
TI  - Doppler Evidence of Intervillous Flow in the Embryonic Period
AB  - >The characterization of the nature and time of onset of intervillous blood flow
      has been the subject of much recent debate. This review advances several
      hypotheses regarding the physiology of intervillous flow and summarizes the human
      and monkey evidence that currently exists. As foundational to the discussion, the
      historical light microscopic data is presented, and this is then coupled with
      illustrations from current ultrasound work that involves pulsed wave Doppler,
      color amplitude imaging, and color Doppler imaging. The evidence clearly suggests
      that intervillous flow is a normal and consistent finding in the early first
      trimester pregnancy.

PMID- 9524153
TI  - Clinical and Sonographic Estimates of Birth Weight Among Diabetic Parturients
AB  - >Objective: To determine the relative accuracy of clinical and sonographic
      estimates of fetal weight (EFW) among parturients with diabetes requiring insulin
      (White's classifications A2 and higher).Methods: In early labor, clinical EFW was
      followed by sonographic mensuration of fetal parts. At the completion of the
      study, sonographic EFW was calculated using abdominal circumference and femur
      length. Student's t test, Wilcoxan test, and chi square test were used to assess
      the relative accuracy of the two methods of assessing birth weight.Results: Among
      94 parturients with various classifications of diabetes, the clinical estimate of
      birth weight has a significantly higher simple error (-180.3 + 419.5 g) but not a
      significantly higher mean standardized absolute error (130.7 +/- 130.1 g/kg) than
      sonographic prediction (-139.3 +/- 447.1 g, 115.6 +/- 90.8 g/kg, respectively).
      Analysis of the data, according to gestational age, indicates that clinical EFW
      is more accurate than sonographic EFW among term (n = 67) parturients with
      diabetes, but both methods are comparable in preterm (n = 27) parturients.
      However, when the data are analyzed according to birth weight, EFW by Leopold
      maneuvers is significantly more accurate than those obtained sonographically in
      infants weighing 2500-3999 g (n = 66) and >4000 g (n = 12).Conclusion: In term
      gestations of diabetic mothers and those infants with a birth weight of 2500 g or
      more, the clinical estimate of birth weight is more accurate; however, in preterm
      diabetic pregnancies, clinical and sonographic estimates are equal.

PMID- 9524154
TI  - Maternal Meal Ingestion Does Not Affect Amniotic Fluid Index during Short-period
      Observation in Normal Pregnancy
AB  - >Objective: To determine whether maternal meal ingestion affects amniotic fluid
      index (AFI) over a short period after maternal meal ingestion in normal growth
      fetuses with normal amniotic fluid volume in uncomplicated late
      pregnancies.Methods: Twenty-five women with an appropriate-for-gestational-age
      fetus with normal AFI were included in a simple crossover, blinded study during
      late pregnancy. After an overnight fast, two different maternal meal states were
      prepared. On day A, the subjects had a standard 600-kcal breakfast at 8 a.m. On
      day B, the fasting state was maintained until 10 a.m. Both states were randomly
      assigned to each woman within 3 days. On both days, the AFI was measured at 7
      a.m. (the fasting state) and at 10 a.m. (the fed state on day A and the
      continuous fasting state on day B). A change in AFI between 7 and 10 a.m. was
      compared between the days by paired t test.Results: The mean gestational age
      (mean +/- SD) was 37.5 +/- 1.5 weeks on day A and 37.4 +/- 1.6 weeks on day B.
      The change in AFI between 7 and 10 a.m. was 1.1 +/- 3.0 cm on day A (with
      breakfast) and 2.1 +/- 2.6 cm on day B (keeping fast). These changes were not
      different between the days (P = 0.19).Conclusions: Maternal meal ingestion had no
      apparent acute effect on AFI in normal growth fetuses with normal amniotic fluid
      volume.

PMID- 9524155
TI  - Decreased Approximate Entropy of Heart Rate Variability in the Hypoxic Ovine
      Fetus
AB  - >Objective: Variability of the fetal heart rate (FHR) is used clinically to
      assess fetal well being. Approximate entropy (ApEn) is a statistic that
      quantifies the regularity of a time series. This study was designed to test
      whether ApEn changed in the FHR of the hypoxic ovine fetus.Methods: Five time
      bred ewes at 130 days of gestation were surgically prepared with fetal arterial
      catheters, fetal electrodes, and a maternal common uterine artery snare occluder.
      After recovery, a continuous fetal electrocardiogram recording was started, and
      control blood gas measurements were made. The uterine blood flow was then reduced
      with the occluder, and blood gas measurements were repeated at fetal pH 7.20 and
      7.00. The FHR tracing (1,000 beats) was extracted from the fetal
      electrocardiogram tracing at the time of each blood gas. For each heart rate
      tracing, the ApEn was calculated. The significance of changes was assessed using
      analysis of variance for repeated measures.Results: The snare occluder produced
      significant fetal hypoxia and acidosis. Although FHR variability was increased,
      approximate entropy was significantly decreased during periods of hypoxia in the
      ovine fetus.Conclusions: Approximate entropy of the ovine fetus is directly
      related to the degree of hypoxia. The decreased ApEn indicates increased
      regularity in the FHR during hypoxia in spite of the increased variability. ApEn
      may provide insight into the regulatory feedback mechanisms of the fetal heart
      rate during periods of hypoxia.

PMID- 9524156
TI  - Reduction of the Human Placental Vascular Relaxation to Progesterone by
      Gestational Diabetes
AB  - >Background: We have recently described a dose-dependent, endothelium-independent
      relaxation to progesterone in human placental arteries and veins. This receptor
      operated, cAMP-mediated relaxation may be of value in maintaining adequate blood
      flow in the placental circulation.Objective: To investigate if gestational
      diabetes alters this relaxation to progesterone.Study design: Isolated human
      placental vessels from pregnancies complicated by gestational diabetes and well
      matched controls (uncomplicated term pregnancies), incubated in Krebs-bicarbonate
      buffer and submaximally precontracted with KCl, were exposed to cumulative doses
      of progesterone (0.01-30 umol/liter), nitroglycerin (0.001-1 umol/liter),
      arachidonic acid (0.01-10 umol/liter), forskolin (0.01-10 umol/liter) and 5
      hydroxytryptamine (serotonin, 0.01-10 umol/liter).Results: The relaxation to
      progesterone in vessels from patients with gestational diabetes was reduced by 50
      100% in both arteries and veins compared with control (for example, relaxation to
      10 umol/liter progesterone was reduced from 52 +/- 7 to 18.8 +/- 5.4% in arteries
      and from 58 +/- 8 to 19 +/- 5.2% in veins, n = 7-13, P < 0.05), whereas responses
      to the other vasoactive agents were unchanged.Conclusion: Based on these results,
      gestational diabetes significantly reduces the relaxation to progesterone in
      human placental vessels. This alteration of the relaxation to progesterone may
      lead to an increase in placental vascular resistance and possibly to a reduction
      of placental blood flow.

PMID- 9524157
TI  - An Assessment of Amniotic Fluid Index Among Japanese (A Longitudinal Study)
AB  - >Objective: To obtain a longitudinal gestational reference range for the amniotic
      fluid index (AFI) among Japanese women and to compare the study with those of
      previous reports.Methods: A total of 739 measurements of the AFI of 96 Japanese
      women with normal pregnancies were analyzed. The criteria were singleton
      pregnancies between 20 and 40 weeks, without fetal anomalies, diabetes mellitus,
      hypertension, and other maternal complications. Logarithmic transformation was
      used to obtain the predicted mean AFI values with 95% confidence intervals at
      each gestational week.Results: The AFI rose from 20 weeks reaching its peak at 30
      weeks. After the peak, it declined toward 40 weeks. Comparison of this study with
      previously published reports revealed differences in the mean AFI
      values.Conclusions: We obtained the gestational age-specific value of AFI in
      normal pregnancy for Japanese women.

PMID- 9524158
TI  - Variability of Murine Pregnancy Outcome Resulting from Passive Immunization with
      Anticardiolipin Antibody-Positive Immunoglobulin G
AB  - >Objective: Administration of purified human IgG from antiphospholipid syndrome
      patients has not consistently caused murine pregnancy loss despite the presence
      of significant anticardiolipin antibody (ACA) activity. We evaluated whether a
      correlation exists between ACA activity and the degree of fetal resorption in
      murine pregnancy and also determined whether pooled IgG from multiple ACA
      positive patients increases the likelihood of fetal resorption compared with
      injection of single-donor IgG.Methods: Affinity chromatography followed by
      anisotropic ultrafiltration was used to extract and concentrate IgG from
      individual serum samples with and without ACA activity (ACA-positive IgG
      activity, 35-85 GPL versus ACA-negative IgG activity, <1 GPL) and from pooled
      aliquots derived from the same sera. On Day 8 of gestation, pregnant mice
      randomly received intraperitoneal injections of ACA-positive or ACA-negative,
      purified IgG (15 mg/mouse) or saline (1 ml). Laparotomies were performed on day
      15, and uteri were harvested for gross evaluation and histologic study. Rates of
      fetal resorption were derived for each murine pregnancy (resorbed
      fetuses/resorbed fetuses + live pups) and compared between experimental
      groups.Results: A significant increase in fetal resorption rate was observed in
      ACA-positive IgG-treated animals (n = 19, 19.3%) compared with either ACA
      negative (n = 5, 6.4%; P = 0.008) or saline-treated pregnancies (n = 8, 4.6%; P =
      0.004). However, differences in resorption rates among the ACA-positive IgG
      treated pregnancies did not correlate with initial ACA activity of the whole
      serum or with antibody activity measured in the purified, concentrated IgG
      preparations. A comparison of fetal resorption between single donor ACA-positive
      IgG and pooled ACA-positive IgG revealed similar rates of fetal resorption (20.5
      versus 17.9%, respectively) but a lower mean birth weight among non-resorbed pups
      in the single-donor IgG-treated pregnancies (340 versus 430 mg; P =
      0.05).Conclusions: Although greater murine fetal resorption resulted from ACA
      positive IgG administration compared with ACA-negative IgG or saline injection,
      marked variability in pregnancy outcome was observed among ACA-positive animals.
      These differences were not attributable to initial antibody activity in whole
      serum or to activity associated with the purified immunoglobulins. Combining
      multiple ACA-positive sera did not augment the rate of fetal resorption.

PMID- 9524159
TI  - Caffeine and Nicotine: Effects on Human Placental Vascular Tone In Vitro
AB  - >Objective: To investigate if the adverse effects caffeine and nicotine have on
      the fetus are mediated by placental vascular tone alterations.Study Design:
      Isolated human placental arteries and veins at resting tone in the presence and
      absence of endothelium were exposed to cumulative doses of caffeine (0.1 nm-0.1
      mm), nicotine, and cotinine (1.0 nm-1.0 mm). Some of the vessels were
      submaximally precontracted with U44619 prior to exposure to cumulative doses of
      the drugs. Dose-response curves to serotonin, KCl, U46619, and prostaglandin
      F2alpha were also obtained in the presence or absence of caffeine, nicotine, and
      cotinine (0.1 mm).Results: Caffeine did not alter vascular tone in human
      placental arteries and veins at resting tone (n = 10). Modest relaxations (15-30%
      of maximal tone) were noted with the addition of the drug to precontracted
      placental blood vessels. Similarly, nicotine and cotinine had no effect on
      resting tone in placental blood vessels, whereas small relaxations (6-10% of
      maximal tone) occurred in vessels precontracted with U46619 (n = 7-10).
      Additionally caffeine (n = 6-10), nicotine, and cotinine failed to alter the dose
      response curves to other contractile agents (n = 7-10).Conclusions: Based on
      these results caffeine, nicotine, and the nicotine metabolite cotinine do not
      appear to alter human placental vascular tone in vitro. These results suggest
      that the adverse effects of these drugs on the fetus during pregnancy are
      unlikely to be due to changes in placental vascular tone.

PMID- 9524160
TI  - Cytokine Response to Fetal Cardiac Bypass
AB  - >Objective: Cytokines are associated with the systemic inflammatory response
      syndrome that occurs after cardiopulmonary bypass. We hypothesized that the
      placental dysfunction which has been found to complicate fetal cardiac bypass may
      be in part a function of a cytokine-mediated acute phase reaction. To test this
      hypothesis, we designed a study to investigate the effect of cardiac bypass on
      interleukin-1beta (IL-1beta), IL-6, and IL-8 in fetal sheep.Methods: Nine mixed
      breed pregnant ewes at 118-122 days of gestation were assigned randomly to either
      the "fetal cardiac bypass group" (n = 5) or the "control group" (n = 4). After
      surgical exposure and instrumentation, cardiac bypass was performed for 30 min in
      study group fetuses, whereas control group fetuses were exposed and instrumented
      identically but did not undergo bypass. Placental and systemic hemodynamics were
      monitored in both groups. Pre- and post-bypass blood samples were analyzed for IL
      1beta, IL-6, and IL-8 using enzyme-linked immunosorbent assays.Results: IL-6
      levels were undetectable before bypass in all fetuses. IL-6 increased after
      bypass in all bypass group fetuses to 53.0 +/- 24.2 pg/ml, whereas IL-6 levels
      remained undetectable in all control animals. Fetal cardiac bypass produced no
      significant changes in IL-1beta and IL-8 in either group. Following bypass,
      placental blood flow decreased by 23% in the bypass group, which was
      significantly more (P = 0.0002) than the 6% decrease in the control group;
      placental vascular resistance increased significantly more in the bypass group
      (20%) than in control fetuses (1%; p = 0.004).Conclusions: Fetal cardiac bypass
      produces significant and consistent increases in fetal plasma IL-6, which
      correlate with increased placental vascular resistance and decreased placental
      blood flow. IL-6 may have an important role in placental dysfunction following
      fetal cardiac bypass, but further investigation will be necessary to elucidate
      its specific role in the impairment of placental function or as a marker of
      placental injury.

PMID- 9524188
TI  - The role of NF-kappaB in retinal neovascularization in the rat. Possible
      involvement of cytokine-induced neutrophil chemoattractant (CINC), a member of
      the interleukin-8 family.
AB  - Hypoxia precedes neovascularization in many retinal diseases that can lead to
      irreversible vision loss. The transcription factor NF-kappaB is activated by
      hypoxia and regulates the expression of many genes, including angiogenic factors.
      The relation between the NF-kappaB activation and the cytokine-induced neutrophil
      chemoattractant (CINC), a member of the interleukin-8 (IL-8) family, was
      investigated by immunohistochemistry in a rat model of proliferative retinopathy
      presumably caused by relative hypoxia. Activated NF-kappaB and CINC
      immunoreactivity was detected in retinal glial cells in the nonperfused retina
      and in neovascular cells. Activated NF-kappaB was detected before the CINC
      staining, and both of these events occurred before the development of
      neovascularization. The intensity of both activated NF-kappaB and CINC staining
      remained increased during the development of neovascularization and then declined
      as neovascularization regressed. In rat retinal glial cells in vitro,
      dexamethasone, an inhibitor of NF-kappaB activation, prevented the hypoxia
      induced increase in the amount of CINC mRNA. Furthermore, CINC induced
      neovascularization in a rat corneal pocket model. These results suggest that
      hypoxia-induced activation of NF-kappaB results in CINC production and
      participates in the induction of retinal neovascularization.

PMID- 9524189
TI  - Human TIMP-3 is expressed during fetal development, hair growth cycle, and cancer
      progression.
AB  - We studied the expression and regulation of TIMP-3, a recently cloned member of
      the tissue inhibitor of the metalloproteinase family, during human fetal
      development and in various human tissues, with emphasis on epithelial structures.
      Expression of TIMP-3 mRNA was detected by in situ hybridization in developing
      bone, kidney, and various mesenchymal structures. At 16 weeks of gestation,
      ectoderm-derived cells of hair germs expressed TIMP-3 mRNA, and beginning from
      the twentieth week consistent expression was detected in epithelial outer root
      sheath cells of growing hair follicles. In normal adult human skin, expression of
      TIMP-3 mRNA was limited to hair follicles, starting at the early anagen (growing)
      phase and vanishing at the catagen (regressing) phase. TIMP-3 mRNA was not
      detected in benign hair follicle-derived tumors but was present in tumor cells of
      infiltrative basal cell carcinomas and in surrounding stromal cells in squamous
      cell carcinomas. Human primary keratinocytes in culture expressed TIMP-3 mRNAs,
      the levels of which were upregulated by transforming growth factor-beta (TGF
      beta), whereas interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF
      alpha) had no effect. Our results suggest a role for TIMP-3 in connective tissue
      remodeling during fetal development, hair growth cycle, and cancer progression.

PMID- 9524190
TI  - Distribution of dystroglycan in normal adult mouse tissues.
AB  - Dystroglycan is a cell surface protein which, in muscle, links the extracellular
      matrix protein laminin-2 to the intracellular cytoskeleton. Dystroglycan also
      binds laminin-1 and the binding occurs via the E3 fragment of laminin-1.
      Recently, it was found that dystroglycan is expressed in developing epithelial
      cells of the kidney. Moreover, antibodies against dystroglycan can perturb
      epithelial development in kidney organ culture. Therefore, dystroglycan may be an
      important receptor for cell-matrix interactions in non-muscle tissues. However,
      information about the tissue distribution of dystroglycan is limited, especially
      in adult tissues. Here we show that dystroglycan is present in epithelial cells
      in several non-muscle organs of adult mice. Dystroglycan is enriched towards the
      basal side of the epithelial cells that are in close contact with basement
      membranes. We suggest that dystroglycan is involved in linking basement membranes
      to epithelial and muscle cells. Dystroglycan may be important for the maintenance
      of tissue integrity.

PMID- 9524191
TI  - Pex mRNA is localized in developing mouse osteoblasts and odontoblasts.
AB  - Mutations in PEX, a phosphate-regulating gene with homology to endopeptidase on
      the X chromosome, were recently identified in patients with X-linked
      hypophosphatemia (XLH), an inherited disorder of phosphate homeostasis
      characterized by growth retardation and rachitic and osteomalacic bone disease.
      To understand the mechanism by which loss of PEX function elicits the mutant
      phenotype, a study of its mRNA localization and ontogenesis was undertaken. Using
      the reverse transcriptase-nested polymerase chain reaction (RT-nested PCR) with
      polyA+ RNA purified from mouse testis, a 337-bp Pex cDNA fragment was generated
      and cloned in the pCRII plasmid. The cDNA was used to generate sense and anti
      sense Pex riboprobes for in situ hybridization (ISH) and Northern analysis. To
      survey a large number of different tissues, sagittal sections of embryos and
      newborn mice were examined. ISH showed the presence of Pex mRNA in osteoblasts
      and odontoblasts. Pex gene expression was detectable on Day 15 of embryonic
      development, which coincides with the beginning of intercellular matrix
      deposition in bones. Finally, Northern analysis of total RNA from calvariae and
      teeth of 3-day-old and adult mice showed that the abundance of the 7-kb Pex
      transcript is decreased in adult bones and in nongrowing teeth. The present study
      demonstrates that Pex mRNA is expressed in bones and teeth and suggests that this
      putative endopeptidase plays an important role in the development of these
      tissues.

PMID- 9524193
TI  - 1,25-Dihydroxy vitamin D3 and tri-iodothyronine stimulate the expression of a
      protein immunologically related to osteocalcin.
AB  - Osteocalcin (OC), a bone-specific protein, is a marker of late osteoblastic
      differentiation. Its expression is influenced by various growth factors and
      hormones. We investigated the effect of 1, 25-dihydroxy vitamin D3 (D3) and tri
      iodothyronine (T3) on OC expression in osteoblast-like MC3T3-E1 cells. A
      heterologous OC green fluorescence protein (GFP) fusion vector was established
      and expressed to study possible effects on protein transport. Immunostaining of
      endogenous OC revealed a significant increase in the percentage of positive cells
      after D3 and T3 treatment. This was consistent for MC3T3-E1 cells as well as
      nonosteogenic NIH-3T3 and mammary carcinoma cells, but not for neuroblastoma
      cells. The perinuclear immunostaining corresponded to the NBD C6 ceramide Golgi
      staining. Conversely, we found a strong induction of OC in MC3T3-E1 cells at the
      mRNA and protein levels only with T3 and not with D3. OC mRNA and protein
      expression was not detected in NIH fibroblasts. OC GFP transfection experiments
      indicate rapid transport and secretion of OC, because OC GFP was not found to be
      accumulated at intracellular compartments after hormone treatment. We conclude
      that the strong perinuclear immunostaining does not represent OC but a protein
      immunologically related to OC, as indicated by preabsorption experiments. The
      expression of this OC epitope-sharing protein is regulated by both D3 and T3 in
      the osteoblastic MC3T3-E1 and in nonosteogenic cells.

PMID- 9524192
TI  - Epitopes of components of the plasminogen activation system are re-exposed in
      formalin-fixed paraffin sections by different retrieval techniques.
AB  - We present a systematic analysis of the sensitivity and specificity of
      immunohistochemical stainings for components of the plasminogen activation
      system, i.e., uPA, tPA, PAI-1, PAI-2, and uPAR, on routinely processed (formalin
      fixed, paraffin-embedded) tissues. Five to nine antibodies per component were
      tested and the influence of different antigen retrieval regimens on
      immunoreactivity was investigated. We studied six different microwave-mediated
      pretreatments and two pretreatments by proteolytic digestion. First, positive and
      negative control tissues were stained. Then, frozen and paraffin sections from
      the same cancer lesions were stained after specific modes of pretreatment and
      with selected antibodies. For each component, one or a few of the tested Abs gave
      optimal staining on paraffin sections when combined with a particular tissue
      pretreatment. For PAI-1, and to a lesser degree also for tPA, an
      underrepresentation of stromal cell staining in paraffin material was found,
      whereas tumor cells showed good staining. For uPA, PAI-2, and uPAR, consistent
      staining results were obtained on paraffin sections.

PMID- 9524194
TI  - Herpes simplex virus type 1-infected human embryonic lung cells studied by
      optimized immunogold cryosection electron microscopy.
AB  - Herpes simplex virus type 1 (HSV-1) is a common human pathogen of skin and mucous
      membranes and is potentially dangerous when the infection is disseminated. Viral
      morphogenesis, especially the mechanism of viral envelopment and the exact
      pathway for processing and transport of HSV-1 glycoproteins, is still unclear. We
      report the results of optimized immunogold-labeled cryosection electron
      microscopy of HSV-1-infected cultured human fibroblasts (MRC-5). The simplified
      method presented has proved necessary to obtain reproducible results on cellular
      distribution of viral glycoproteins. It is now possible to demonstrate the viral
      glycoprotein gD-1, but not gC-1, in the nuclear membranes and to demonstrate gD-1
      and gC-1-labeled viral particles in the perinuclear space, and to show the fate
      of the viral particles in the endoplasmic reticulum and Golgi area in infected
      cells.

PMID- 9524195
TI  - Immunohistochemistry of carbonic anhydrase isozyme IX (MN/CA IX) in human gut
      reveals polarized expression in the epithelial cells with the highest
      proliferative capacity.
AB  - MN/CA IX is a recently discovered member of the carbonic anhydrase (CA) gene
      family that has been identified in the plasma membranes of certain tumor and
      epithelial cells and found to promote cell proliferation when transfected into
      NIH3T3 cells. This study presents localization of MN/CA IX in human gut and
      compares its distribution to those of CA I, II, and IV, which are known to be
      expressed in the intestinal epithelium. The specificity of the monoclonal
      antibody for MN/CA IX was confirmed by Western blots and immunostaining of COS-7
      cells transfected with MN/CA IX cDNA. Immunohistochemical stainings of human gut
      revealed prominent polarized staining for MN/CA IX in the basolateral surfaces of
      the enterocytes of duodenum and jejunum, the reaction being most intense in the
      crypts. A moderate reaction was also seen in the crypts of ileal mucosa, whereas
      the staining became generally weaker in the large intestine. The results indicate
      isozyme-specific regulation of MN/CA IX expression along the cranial-caudal axis
      of the human gut and place the protein at the sites of rapid cell proliferation.
      The unique localization of MN/CA IX on the basolateral surfaces of proliferating
      crypt enterocytes suggests that it might serve as a ligand or a receptor for
      another protein that regulates intercellular communication or cell proliferation.
      Furthermore, MN/CA IX has a completely conserved active site domain of CAs
      suggesting that it could also participate in carbon dioxide/bicarbonate
      homeostasis.

PMID- 9524196
TI  - Cytoplasmic carbonic anhydrase II of rat coagulating gland is secreted via the
      apocrine export mode.
AB  - Two different pathways for protein secretion are described for epithelial cells
      of rat coagulating gland and dorsal prostate: the classical merocrine and the
      alternative apocrine release mode. Apocrine-secreted proteins are synthesized on
      cytoplasmic polyribosomes and are subsequently exported in protrusions on the
      apical cell surface (aposomes). In this article we report the identification and
      purification to homogeneity of a 29-kD protein from the secretion of rat
      coagulating gland. N-terminal amino acid sequence analyses revealed 100% identity
      to rat brain carbonic anhydrase II (CAH II). In addition, the 29-kD protein
      showed CAH enzyme activity. On Western blot analysis, a polyclonal anti-CAH II
      antibody raised in rabbit reacted specifically with the rat and human but not
      bovine CAH II isoforms. Immunohistochemical studies on rat coagulating gland
      showed strong labeling for CAH II protein in aposomes. Immunoelectron microscopy
      confined CAH II protein to the cytoplasm and aposomes, whereas no staining was
      visible in the compartments of the classical merocrine route, the endoplasmic
      reticulum and Golgi apparatus. The resident cytoplasmic protein lactate
      dehydrogenase, however, was not found in the secretion. Taken together, the
      morphological and biochemical data clearly indicate that cytoplasmic CAH II from
      rat coagulating gland is specifically selected and then secreted via the apocrine
      pathway.

PMID- 9524197
TI  - Different pattern of MRP localization in ciliated and basal cells from human
      bronchial epithelium.
AB  - The MRP (multidrug resistance-associated protein) transmembrane transporter,
      which actively transports a wide variety of lipophilic substrates out of cancer
      cells, has been suggested to play a major role in cell detoxification via efflux
      of glutathione conjugates. Because bronchial epithelial cells are constantly
      exposed to environmental pollutants, MRP might be a particularly important
      defense mechanism against xenobiotics. This study was therefore designed to
      investigate MRP localization by immunohistochemistry in bronchial epithelial
      cells collected by scraping from surgical specimens. In parallel, MRP mRNA was
      detected by reverse transcriptase chain reaction (rt-PCR) in bronchial cell
      lysates. However, the pattern of protein expression differed markedly according
      to cell type. In ciliated epithelial cells, immunostaining was restricted to the
      basolateral surface, without any labeling at the apical surface, which is at
      variance with the localization of CFTR and MDR1 proteins, other members of the
      same family of transporters. In basal cells, MRP was present over the entire
      circumference of the plasma membrane. Basal cells were identified by their
      morphology and specifically after incubation with an anticytokeratin 17
      monoclonal antibody. In conclusion, the different patterns of localization
      suggest specific roles for MRP in basal and ciliated cells.

PMID- 9524200
TI  - Detection of human papillomavirus in archival tissues. Comparison of in situ
      hybridization and polymerase chain reaction.
AB  - Formalin-fixed, paraffin-embedded tissues in pathology archives are an important
      resource for molecular epidemiology studies. Use of these tissues requires that
      assays be optimized to account for inevitable variations in tissue fixation and
      processing that occur in the performance of routine histology. We compared
      results of colorimetric in situ hybridization (ISH) to L1 consensus polymerase
      chain reaction (PCR) for detection and typing of human papillomavirus (HPV) in
      180 blocks of archival tissues (up to 9 years in storage) from cervical cancer
      patients. Fifteen samples could not be amplified by PCR, but assays were
      concordant in 75.1% (124/165) of samples that could be analyzed by both methods.
      Similar numbers of ISH+/PCR- (23) and ISH-/PCR+ (18) cases were found. Eight of
      the 18 ISH-/PCR+ cases were attributable to PCR detection of HPV types not
      included in the ISH assay. This degree of concordance required individual
      optimization of assay conditions for each block. ISH and PCR assays for HPV yield
      complementary results, and both can be successfully applied to archival tissues.

PMID- 9524198
TI  - Cellular localization of calmodulin-dependent protein kinases I and II to A-cells
      and D-cells of the endocrine pancreas.
AB  - Ca2+/calmodulin-dependent protein kinases I and II, initially identified in brain
      on the basis of their ability to phosphorylate synapsin I, have been implicated
      in the regulation of Ca2+-dependent synaptic neurosecretion. Specific recombinant
      and synthetic peptide antibodies were used to examine the distribution of CaM
      kinases I and II in the rat pancreas and other tissues. The CaM kinase I
      antibodies detected a doublet of cytosolic proteins of approximately 38 and
      approximately 42 kD by immunoblot. CaM kinase I was observed in glucagon
      containing A-cells at the periphery of the islet of Langerhans but had little or
      no overlap with pancreatic polypeptide or somatostatin cells. In contrast, CaM
      kinase II was localized to somatostatin-containing D-cells. CaM kinase I co
      localized with glucagon secretory granules. CaM kinase II was not associated with
      the somatostatin granule but rather was enriched in areas of the cells that
      contained relatively little somatostatin. Because glucagon secretion is Ca2+
      dependent, it is attractive to speculate that CaM kinase I may play a regulatory
      role in glucagon secretion. Glucagon and somatostatin cells both utilize
      intracellular Ca2+ for signaling. Therefore, specific CaM kinases may act as
      effectors of Ca2+ in these different cell types.

PMID- 9524201
TI  - Characterization of the promoter region and genomic organization of GLI, a member
      of the Sonic hedgehog-Patched signaling pathway.
AB  - GLI is the prototype for the Gli-Kruppel gene family characterized by a consensus
      C2-H2 zinc finger domain and is believed to function as a transcription activator
      in the vertebrate Sonic hedgehog-Patched signal transduction pathway.
      Understanding GLI gene regulation may be of importance to understanding causes of
      human birth defects and cancer. To begin to understand the regulation of this
      developmentally important gene we have cloned the human GLI gene and functionally
      characterized its 5' flanking region. The GLI gene is composed of 12 exons and 11
      introns and in the zinc finger coding region shares a highly conserved splicing
      pattern with several other Gli family members in both vertebrates and C. elegans.
      A major transcription initiation site was identified upstream of the GLI
      translation start site along with three minor transcription initiation sites. The
      region surrounding the transcription initiation sites lacks TATA and CCAAT
      consensus sequences, has a high GC content, includes a CpG island, and contains
      several GC boxes. A 487bp segment surrounding the transcription initiation sites
      increased expression of a luciferase reporter gene 15-fold in Tera-1 cells and
      was defined as the core promoter region of human GLI. In transgenic mice this
      region directed beta-galactosidase expression to the central nervous system on
      embryonic days 10.5-12.5 and to sites of endochondral ossification on embryonic
      days 12.5 and 13.5 in a pattern comparable to the endogenous expression pattern
      of mouse gli within these tissues. The previously identified gastrointestinal
      expression of gli was not driven by this region and may require elements outside
      of the core promoter. Sequence analysis of the 5' flanking region of the mouse
      gli gene and the full-length mouse gli cDNA demonstrated high homology with human
      GLI, suggesting conservation of GLI regulation and function.

PMID- 9524202
TI  - Novel structural difference between nopaline- and octopine-type trbJ genes:
      construction of genetic and physical map and sequencing of trb/traI and rep gene
      clusters of a new Ti plasmid pTi-SAKURA.
AB  - We constructed a gene library of a nopaline-type Ti plasmid (called pTi-SAKURA)
      which was newly isolated from Agrobacterium tumefaciens MAFF301001 of a Japanese
      cherry tree. The partial sequencing data, which were distributed over the entire
      plasmid genome, made it possible to assign typical Ti-encoded genes including trb
      and rep gene clusters. The trb/traI and rep gene clusters were sequenced
      completely. All the genes in the regions except trbJ were homologous with the
      corresponding genes on octopine-type Ti plasmids, based on both ORF size and
      sequence similarity. The trbJ on pTi-SAKURA is similar to that of an octopine
      type Ti, but has an extra 282-base segment in its central domain. The above gene
      organization and sequences suggest a divergence of Ti plasmid during evolution in
      relation to Rhizobium plasmids, and is discussed in this paper.

PMID- 9524203
TI  - Methylation-mediated regulation of the glutathione S-transferase P1 gene in human
      breast cancer cells.
AB  - Understanding the mechanisms that regulate the human pi class GST (GSTP1) gene
      expression in breast cancer cells is of particular importance to the study of
      breast cancer biology. In cultured human breast cancer cell lines, GSTP1 is
      exclusively expressed in estrogen receptor-negative (ER-) cells but is
      undetectable in receptor-positive (ER+) cells. Previously, we examined
      transiently transfected GSTP1 promoter activities, in vitro GSTP1 promoter-DNA
      interactions, and GSTP1 mRNA stability. These studies indicated that transiently
      transfected GSTP1 promoter elements and GSTP1 mRNA stability could only partially
      explain cell line-specific expression of endogenous GSTP1. In the present study,
      we examined whether the methylation status of the GSTP1 CpG island plays an
      important role in GSTP1 regulation. Southern blot analysis revealed that the
      GSTP1 CpG island is hypermethlyated in ER+, GSTP1 non-expressing cell lines but
      is undermethylated in ER-, GSTP1 expressing cell lines. Moreover, partial
      demethylation of the GSTP1 CpG island by treatment with 5-aza-2'-deoxycytidine
      resulted in de novo gene expression in ER+ cell lines, as detected by RT-PCR,
      Northern blot and Western blot analyses. Our data strongly indicate that
      methylation status of the promoter contributes significantly to the levels of
      GSTP1 expressed in ER- and ER+ breast cancer cell lines.

PMID- 9524204
TI  - Cloning and expression of Escherichia coli 5'-methylthioadenosine/S
      adenosylhomocysteine nucleosidase: identification of the pfs gene product.
AB  - The enzyme 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase (EC
      3.2.2.9) is responsible for cleavage of the glycosidic bond in both 5'
      methylthioadenosine (MTA) and S-adenosylhomocysteine (SAH). Based on amino acid
      sequence analysis of this enzyme from Klebsiella, we recently speculated that an
      open reading frame found in E. coli (designated pfs) encoded MTA/SAH
      nucleosidase. To explore this possibility, we amplified, cloned, and expressed
      the complete pfs gene from E. coli genomic DNA. The recombinant protein exhibited
      a molecular weight and Michaelis constants for MTA that are in agreement with
      those reported for native enzyme. From this biochemical evidence we confirm our
      original assignment of the pfs gene as encoding MTA/SAH nucleosidase.

PMID- 9524205
TI  - Genetic complexity of the human geranylgeranyltransferase I beta-subunit gene: a
      multigene family of pseudogenes derived from mis-spliced transcripts.
AB  - Geranylgeranyltransferase I controls the function of a variety of cellular
      proteins by attaching a geranylgeranyl group to the carboxy-terminus of proteins.
      The purified enzyme from rat brain is comprised of two polypeptides, a catalytic
      alpha-subunit (GGTalpha) and a substrate-binding beta-subunit (GGTbeta). The
      present paper demonstrates the existence of a GGTbeta multigene family in humans
      by describing the presence and characterization of at least 13 pseudogenes
      related to this protein. Sequencing of numerous PCR-derived clones, obtained
      following amplification of human genomic DNA, revealed multiple, distinct but
      highly related sequences. All clones had a common deletion of 99-bp that conforms
      to the GT-AG rule of splicing in eukaryotes, and differed from the human GGTbeta
      cDNA sequence by multiple nucleotide substitutions. PCR amplification from mRNA,
      however, yielded only the sequence expected for the expressed GGTbeta protein.
      This apparent paradox was resolved by cloning and sequencing a complete GGTbeta
      specific pseudogene. Multiple features of the cloned gene, in particular the
      absence of introns, presence of flanking direct repeats, and the lack of sequence
      similarity with the untranscribed region of the gene, indicate that this clone
      represents a processed pseudogene possibly resulting from a mis-spliced
      transcript. Multiple GGTbeta-specific pseudogenes appear to have resulted from
      more than one retroposition event. These results suggest a potential role for mis
      splicing in the evolutionary diversity of pseudogenes.

PMID- 9524206
TI  - Cloning and chromosomal localization of a paralog and a mouse homolog of the
      human transaldolase gene.
AB  - A sequence homologous to the transaldolase gene (TALDO) was identified in a
      polymorphic cosmid DNA mapped on human chromosome 11p15 by exon trapping with
      pSPL3. Analysis of lambda clones contiguous to the cosmid clone showed that the
      related gene (TALDOR) consists of 8 exons spanning approximately 19kb from the
      translation start site to the polyadenylation signal. The exon sequence of TALDOR
      was almost identical with that of TALDO localized on 1p33-34. 1, but its exons
      corresponding to exons 4 and 5 of TALDO were found to be split by 4 introns in
      TALDOR. To examine the evolutionary conservation of two genes for transaldolase,
      we have isolated the cDNA for its mouse homolog and determined the nucleotide
      sequence covering the complete coding region. Fluorescence in situ hybridization
      using the cDNA as a probe showed that the mouse transaldolase gene (Taldo) is
      localized on chromosome 7 F3-F4 as a single copy gene. This chromosomal region is
      known to be syntenic to human chromosome 11p15 rather than to 1p33-p34.1,
      suggesting that TALDOR is the ancestral form. The existence of TALDOR implies a
      duplication of the mammalian transaldolase gene after divergence of rodent and
      primate.

PMID- 9524207
TI  - Schizosaccharomyces pombe apn1 encodes a homologue of the Escherichia coli
      endonuclease IV family of DNA repair proteins.
AB  - The Apn1 protein of the budding yeast Saccharomyces cerevisiae is a DNA repair
      enzyme that hydrolyzes apurinic/apyrimidinic (AP) sites and removes 3'-blocking
      groups present at single strand breaks of damaged DNA. Yeast cells lacking Apn1
      are hypersensitive to DNA damaging agents that produce AP sites and DNA strand
      breaks with blocked 3'-termini. In this study, we showed that the fission yeast
      Schizosaccharomyces pombe bears a homologue, Spapn1, that is 45% identical to S.
      cerevisiae Apn1. However, the Spapn1 gene is apparently not expressed. Active
      expression of S. cerevisiae Apn1 in S. pombe conferred no additional resistance
      to DNA damaging agents. These data suggest that the pathway by which S. pombe
      repairs AP sites is independent of a functional Apn1-like AP endonuclease.

PMID- 9524208
TI  - The chicken cDNA for ornithine decarboxylase antizyme.
AB  - Two full length avian cDNAs for ornithine decarboxylase antizyme were isolated
      from a chicken cochlear cDNA library and differed in length through use of
      alternative poly(A) addition signals. The chick antizyme protein sequence
      predicted by translational frameshifting of the mRNA is 216 amino acids long and
      is more similar to Xenopus antizyme than to the mammalian protein.

PMID- 9524209
TI  - Quantitation of age-related mitochondrial DNA deletions in rat tissues shows that
      their pattern of accumulation differs from that of humans.
AB  - Three age-related mtDNA deletions were identified, and the competitive polymerase
      chain reaction (PCR) was used to quantitate their levels in different Fisher 344
      rat tissues. Deletions that removed 4834; 13273; or 13415nt of the mitochondrial
      genome were shown to be associated with 16 (mtDNA4834), nine (mtDNA13273), or
      five (mtDNA13415) nt direct repeats, respectively. The mtDNA4834 deletion was
      detected in an age-related manner in all tissues screened; the mtDNA13415
      deletion was detected in old heart, and in both young and old brain; and the
      mtDNA13273 deletion was only detected in old brain tissues. The mtDNA4834
      deletion was found to be at its highest level in the liver (1.88x10-2%), followed
      by the brain (0.22x10-2%) and kidney (0.40x10-2%) of old animals. Much lower
      levels were observed in old heart (0.07x10-2%) and lung (0. 04x10-2%). This
      distribution of mtDNA deletions in old rat tissues is in contrast to work done in
      humans where age-related deletions are present at the highest levels in post
      mitotic tissues with much lower levels in more mitotic tissues. An inverse
      relationship was observed between the level of mtDNA deletions and the size of
      the deleted region, since the mtDNA13415 deletion was present at about a 100-fold
      lower level (0.53x10-5%) than the smaller mtDNA4834 deletion in old heart tissue.

PMID- 9524211
TI  - Cloning and characterization of the gene encoding the iron-sulfur protein of
      succinate dehydrogenase from Pleurotus ostreatus.
AB  - Genomic and cDNA fragments encoding the iron-sulfur protein (Ip) subunit of
      dehydrogenase (EC 1.3.99.1) have been cloned from the edible basidiomycetous
      fungus, Pleurotus ostreatus. The gene is interrupted by five introns and is
      predicted to encode a polypeptide of 268 amino acid residues. Sequence comparison
      with the Ip subunit from other species identified three conserved cysteine-rich
      clusters. One of these contains a critical histidine residue implicated in
      carboxin sensitivity in the heterobasidiomycete Ustilago maydis.

PMID- 9524210
TI  - Evaluation and mapping of the DNA binding and oligomerization domains of the IE2
      regulatory protein of human cytomegalovirus using yeast one and two hybrid
      interaction assays.
AB  - The 86-kDa IE2 nuclear phosphoprotein encoded by the human cytomegalovirus (HCMV)
      major immediate-early (MIE) gene behaves as both a non-specific transactivator of
      viral and cellular gene expression and as a specific DNA-binding protein targeted
      to the cis-repression sequence (CRS) at the cap site of its own promoter/enhancer
      region. Although the IE2 protein produced in bacteria has been shown to bind to
      the 14-bp palindromic CRS motif and IE2 synthesized in vitro forms stable dimers
      in solution through the conserved C-terminus of the protein, there is no direct
      evidence as yet that the intracellular mammalian forms of IE2 do so. Here, we
      show that the intact HCMV IE2 protein both binds to CRS DNA and dimerizes in
      yeast cells. In a one-hybrid assay system, a GAL4/IE2 fusion protein expressed in
      yeast cells activated target HIS3 expression only when CRS sites were located
      upstream of the GAL1 minimal promoter, but failed to do so on mutant CRS sites,
      demonstrating a requirement for sequence-specific DNA-binding by IE2. Examination
      of a series of deletion and triple amino acid point mutations in the C-terminal
      half of IE2 mapped the domains required for DNA-binding in yeast to the entire
      region between codons 313 and 579, whereas in the previous in-vitro study with
      truncated bacterial GST fusion proteins, it was mapped to between codons 346 and
      579. Transient co-transfection assays with deleted IE2 effector genes in Vero
      cells showed that the extra segment of IE2 between codons 313 and 346 is also
      required for both autoregulation and transactivation activity in mammalian cells.
      In a two-hybrid assay to study IE2 self-interations, we generated both GAL4 DNA
      binding (DB) and activation domain (A)/IE2 fusion proteins and showed that IE2
      could also dimerize or oligomerize through the C-terminus of the protein in yeast
      cells. Domains required for this interaction were all mapped to within the region
      between codons 388 and 542, which is coincident with the domain mapped previously
      for dimerization by co-translation and immunoprecipitation in vitro. Comparison
      of the domains of the IE2 protein required for CRS binding and dimerization in
      yeast suggests that these activities correlate precisely with requirements for
      the negative autoregulation function of the IE2 protein in mammalian cells.

PMID- 9524212
TI  - Cloning, sequencing and structural analysis of 976 base pairs of the promoter
      sequence for the rat lipoprotein lipase gene. Comparison with the mouse and human
      sequences.
AB  - We cloned and sequenced the -976bp promoter of the rat lipoprotein lipase LPL
      gene. The sequence was compared with the mouse and human sequences. The homology
      between the rat and mouse LPL nucleotide sequences was not quite as strong in the
      promoter sequence as in the coding sequence. Among the 976nt promoter there were
      118 divergences, i.e. 11.8%, compared to only 5.6% for the LPL coding region.
      However, within the 200nt immediately 5' to the transcriptional start site
      (proximal promoter), the divergence was only 4%. New potential cis-elements (such
      as CACCC, GATA, GC and GA boxes, IRS, Krox, MEF 2, E-box, CCArGG and 1/2 VDRE)
      were identified in the rat, mouse or human LPL gene.

PMID- 9524214
TI  - The single-stranded DNA binding protein, Pur-alpha, binds HIV-1 TAR RNA and
      activates HIV-1 transcription.
AB  - Previous studies indicate that the bulge and loop domains of TAR, the HIV-1 RNA
      regulatory element, bind viral and cellular factors that are critical for
      efficient transcription of the HIV-1 genome. In this report, we demonstrate that
      the cellular protein, Pur-alpha, a previously characterized sequence specific,
      single-stranded DNA binding protein, binds to HIV-1 TAR RNA in a specific manner
      as demonstrated by competition analysis. Pur-alpha binds to the greatest extent
      to wild-type TAR RNA, and it appears the primary sequence, as well as the
      secondary structure and its overall stability contribute to this binding. Results
      from gel shift analysis using mutant Pur-alpha proteins indicate that amino acids
      55-85, which contain the first of three basic aromatic repeats, are important for
      its binding to TAR RNA. Overexpression of Pur-alpha in a glial cell line
      increased transcription of HIV-1 LTR by a TAR dependent mechanism. The potential
      contribution by Pur-alpha to HIV-1 expression in relation to basal transcription
      by cellular factors is discussed.

PMID- 9524213
TI  - Poly A-containing histone H4 mRNA variant (H4-v. 1): isolation and sequence
      determination from bovine adrenal medulla.
AB  - A histone H4 cDNA variant (H4-v.1) was cloned from a bovine adrenal medullary
      phage library using PCR as a method of detection. The isolated clones contained a
      short 5' untranslated region (UTR) followed by the histone H4 coding region and a
      long atypical 3'UTR. The 3'UTR comprised the palindromic and purine-rich
      sequences typical of cell-cycle dependent histone mRNAs, and a 1.1 kb extension
      downstream of the palindromic sequence ending with a poly(A) track typical of
      cell-cycle independent histone mRNAs. Northern blot and RT-PCR analyses indicate
      that the transcript is fully expressed in bovine adrenal medulla. Thus, bovine
      histone H4-v.1 mRNA represents the first example of a histone H4 transcript that
      contains both 3'UTR characteristics of cell-cycle dependent and cell-cycle
      independent histone mRNAs.

PMID- 9524215
TI  - JADE: An approach for interconnecting bioinformatics databases 
AB  - To achieve the integration of biological data available on the World Wide Web and
      maintained in diverse sources such as GDB, Genbank or Acedb, we have developed a
      software called Jade. Jade allows programmers to create analytic tools and
      graphical user interfaces for one or more existing bioinformatics data sources.
      These tools can then be interchanged, compared and reused without making
      modifications in the data sources themselves. The system is implemented in the
      Java programming language and will run equally well on Macintosh, Windows or Unix
      workstations. Jade is free and can be used immediately by all interested parties.

PMID- 9524216
TI  - Sequence analysis of the Porphyromonas gingivalis dipeptidyl peptidase IV gene.
AB  - We previously constructed a Porphyromonas gingivalis genomic library and isolated
      the 2.9 kb EcoRV fragment which specified glycylprolyl dipeptidyl aminopeptidase
      (GPase). Nucleotide sequencing of this fragment identified the single 2169 bp
      open reading frame which coded for a 723 amino acid protein. The amino acid
      sequencing of the NH2-terminal domain of the native and recombinant mature
      enzymes suggested that the protease possessed a 16 amino acid residue signal
      peptide. The calculated mass of the precursor and mature proteases were 82,018
      and 80,235 daltons, respectively. The homology search of this enzyme in
      registered protein sequences revealed that this enzyme was homologous to
      dipeptidyl peptidase (DPP) IV from the Flavobacterium meningosepticum and that
      from eukaryotic cells, including the human, mouse, and rat. Three amino acid
      residues, Ser-593, Asp-668, and His-700, were identified as a putative catalytic
      triad, a common feature of eukaryotic serine proteases. In addition, this enzyme
      showed a broad proteolytic spectrum toward synthetic substrates capable of
      splitting not only Gly-Pro-derivative but also Ala-Pro, Lys-Pro, and Phe-Pro
      derivatives. Therefore, we conclude that this enzyme belongs to DPP IV rather
      than GPase.

PMID- 9524217
TI  - Characterization of a gene from the filamentous fungus Podospora anserina
      encoding an aspartyl protease induced upon carbon starvation.
AB  - In an attempt to characterize proteases associated with vegetative
      incompatibility, a Podospora anserina gene (papA) encoding an aspartyl protease
      (podosporapepsin) was cloned using a heterologous probe. The deduced papA coding
      region was 1278 nucleotides long, interrupted by a single 71bp intron. The
      corresponding amino acid sequence presented a high degree of similarity to other
      aspartyl proteases. Sequence analysis and proteolytic activity measurement
      suggested that the podosporapepsin could be intracellular rather than secreted.
      The papA gene was expressed under carbon starvation, but not under nitrogen
      starvation conditions. Its disruption led to a slight decrease in the growth rate
      of the mutant strain when bovine serum albumin was the sole carbon source in the
      medium. Disruption or overexpression of papA gene had no obvious consequence on
      vegetative incompatibility. Transcription of papA induced by carbon starvation
      was strongly reduced in the presence of a suppressor of vegetative
      incompatibility. This result suggests a relationship between adaptation for
      starvation and vegetative incompatibility.

PMID- 9524218
TI  - Complex organisation of the 5'-end of the human glycine tRNA synthetase gene.
AB  - Glycine tRNA synthetase (glyRS) catalyses the addition of the amino acid glycine
      to its cognate tRNA molecules. In the silk moth worm Bombyx mori, this gene is
      subject to complex transcriptional regulation because of the predominance of
      glycine in silk. In vertebrates, glycine is a major constituent of collagen but
      there have been no studies of glyRS regulation. In this study we have isolated
      and mapped a genomic clone containing the 5'-end of glyRS. Primer extension
      studies identified only one transcriptional start point (TSP) in three different
      cell lines. Expression of the transcript identified may be regulated
      translationally because it contains five potential initiation codons, three of
      which are in good context for initiation. The most 3' of the potential initiation
      codons has previously been predicted to be the initiating codon for cytoplasmic
      glyRS. Two of the upstream codons are in-frame with this codon, and both are
      predicted to extend the N-terminus of glyRS to include a mitochondrial targeting
      sequence. Sequencing of genomic DNA surrounding the TSP showed features common to
      the promoters of housekeeping genes, as well as a canonical TATA box at the
      unusual position of +9. Surprisingly, promoter activity in vitro was not
      specified by a 1.9 kb genomic fragment containing the TSP and TATA box, but by a
      contiguous 0.4 kb fragment immediately downstream. These studies suggest that the
      transcription of glyRS from a single start point requires downstream promoter
      elements.

PMID- 9524219
TI  - Isolation and characterization of a cDNA encoding a high mobility group protein
      HMG-1 from Canavalia gladiata D.C.
AB  - A cDNA clone encoding a HMG-1 protein from maturing seeds of Canavalia gladiata
      was isolated and characterized with respect to its sequence, genomic organization
      and the expression pattern in seeds. The predicted polypeptide had the
      characteristic conserved motifs of the HMG-1/2 protein including N-terminal basic
      region, one HMG-box and polyacidic carboxy terminus. Southern blot analysis
      suggested that the HMG-1 gene is a single copy gene. Northern blot analysis
      indicated that the HMG-1 gene was expressed both in maturing and germinated
      seeds.

PMID- 9524220
TI  - Molecular cloning of the cDNA encoding A + U-rich element RNA binding factor.
AB  - Using the differential display method, a new cDNA clone, termed laAUF1, encoding
      the human A + U-rich RNA-binding motif was isolated and sequenced. Analysis of
      the protein sequence of laAUF1 indicates 73% homology between the deduced
      polypeptide sequences of laAUF1 and AUF1 in the region encoding a consensus motif
      for two non-identical RNA recognition motifs (RRMs) and Gln-rich motif. We
      suggest that the similar affinities of laAUF1 and AUF1 for particular A + U-rich
      elements (ARE) sequences are related to their potencies as mRNA destabilizers.

PMID- 9524221
TI  - The two gamma-tubulin-encoding genes of the ciliate Euplotes crassus differ in
      their sequences, codon usage, transcription initiation sites and poly(A) addition
      sites.
AB  - We have isolated and sequenced two gamma-tubulin (gamma-Tub)-encoding
      macronuclear genes of the ciliate Euplotes crassus (Ec), as well as their
      corresponding cDNAs. Our results reveal that the two genes (gamma-tub 1 and gamma
      tub 2) have introns in homologous positions, but differ in their sequences, codon
      usage, transcription initiation sites and poly(A) addition sites. They both
      consist of three exons, two introns and two short non-coding sequences on both
      ends, and they both code for polypeptides of 462 amino acids (aa). The two genes
      share 76% identity at the nucleotide (nt) level, 86% at the deduced aa level and
      show 61-92% aa homology to the gamma-Tubs of other organisms. The gamma-tub 2
      gene contains two in-frame UGA codons which, like UGA codons in other Euplotes
      genes, probably code for cysteines. No UGA triplet was found in the gamma-tub 1
      gene. Further studies on the cDNA ends indicate that gamma-tub 1 uses at least
      three transcription initiation sites and two poly(A) addition sites. In contrast,
      only one transcription initiation site and one poly(A) addition site were
      identified in gamma-tub 2.

PMID- 9524222
TI  - Utilization of an 86 bp exon generates a novel adducin isoform (beta 4) lacking
      the MARCKS homology domain.
AB  - A novel isoform of beta-adducin has been amplified and characterized from a human
      bone marrow cDNA library (GenBank #U43959). This isoform arises from the
      insertion of an 86 bp alternatively spliced and previously unrecognized exon (now
      termed exon 15) within codon 581 of the human red blood cell beta-adducin
      sequence. This results in an insertion of 28 novel amino acids. The remainder of
      the red cell beta-adducin mRNA is then translated in a different reading frame,
      adding an additional 35 novel amino acids prior to the stop codon. This new
      isoform, thus, replaces beta 1-adducin sequence after residue 580 with a total of
      63 new amino acids. Sequences from genomic clones of the human beta-adducin gene
      show that this alternate exon is flanked by splice consensus sequences and is
      appropriately located in the genomic map between exons encoding up-stream and
      down-stream sequences, thus defining a new exon. The COOH-terminus of this new
      isoform, which we designate beta 4, lacks a 22 amino acid lysine-rich sequence
      common to both the human red cell alpha- and beta-adducin subunits and homologous
      to a highly conserved region in MARCKS, a filamentous actin-cross linking protein
      regulated by protein kinase C and calcium/calmodulin. beta 4-adducin preserves a
      previously identified calmodulin binding domain. PCR analysis indicates that this
      new beta-adducin isoform is expressed in fetal brain and liver, bone marrow, and
      NT-2 (neuroepithelial) cells, but is not detected in several other tissues. We
      anticipate that this new beta 4 isoform of beta-adducin will display unique and
      tissue-specific functional properties.

PMID- 9524223
TI  - Characterization of the human gene coding for the swelling-dependent chloride
      channel ICln at position 11q13.5-14.1 (CLNS1A) and further characterization of
      the chromosome 6 (CLNS1B) localization.
AB  - Expression cloning revealed a chloride channel (ICln) that we found to be
      fundamental for the regulatory volume decrease in a variety of cells. The
      chromosomal localization of the human ICln-gene showed two loci, one at
      chromosome 11 in position q13.5-q14.1, termed CLNS1A, and a second one at
      chromosome 6 at position p12.1-q13, termed CLNS1B. In this study, we offer a
      detailed characterization of the CLNS1A gene and provide the exact position
      (6p12) and sequence data of CLNS1B, an intronless gene 91.3% homologous to the
      coding region of CLNS1A.

PMID- 9524225
TI  - Isolation of an Alu repetitive DNA binding protein and effect of CpG methylation
      on binding to its recognition sequence.
AB  - The structure, expression, and evolution of Alu repetitive DNA elements have been
      extensively studied, but the role of these sequences in the function of primate
      genomes has yet to be elucidated. The contribution of Alu repetitive sequences
      (ARS) to the structure, maintenance, or expression of the human genome is
      undoubtedly mediated by one or more DNA binding proteins. As part of a larger
      study in this laboratory to define the molecular mechanisms that result in de
      repression of the glycoprotein hormone alpha-subunit (GPH alpha) gene in a
      variety of tumor cell types, it was found that the gene was hypermethylated in a
      variety of cell lines that produce alpha-subunit at high levels and significantly
      less methylated in cell lines where the gene is unexpressed or expressed at low
      levels. This is in sharp contrast to the majority of genes examined in this
      regard, which show an inverse correlation between methylation and expression. The
      analysis was extended to a group of clones isolated from a single cell line
      (HeLa) that were differentially methylated over the GPH alpha gene and exhibited
      a 400-fold range in its expression. These analyses demonstrated that methylation
      of a small number of CpG dinucleotides correlated with high level expression of
      the gene. Two of these sites are imbedded in oppositely oriented Alu repeats
      located in the 5'-flanking DNA and second intron. The upstream site was examined
      in some detail. DNase I footprint analysis demonstrated that the protein protects
      a region encompassing the sequence 5'-TTGAACCCGGGAG-3', and electrophoretic gel
      mobility shift analysis demonstrated specific binding of a protein to an
      oligonucleotide containing the DNase footprint sequence. Chromatography of
      nuclear extracts on Sephacryl S-200, heparin--agarose, and oligonucleotide-
      Sepharose produced an apparently homogeneous preparation of the 50-53 kDa DNA
      binding protein as judged by silver staining of sodium dodecylsulfate
      polyacrylamide gels. The affinity-purified material was enriched 15- to 18,000
      fold over crude nuclear extracts. Binding of this protein to an oligonucleotide
      containing the DNase-protected sequence was severely inhibited when CpG
      dinucleotide in the Msp I recognition site was methylated on either the sense or
      antisense strands. Based on its properties, this protein has been termed MeSABp50
      for methylation-sensitive Alu binding protein of 50 kDa.

PMID- 9524224
TI  - The interaction of the Vibrio cholerae transcription factors, Fur and IrgB, with
      the overlapping promoters of two virulence genes, irgA and irgB.
AB  - irgA, a virulence gene in Vibrio cholerae, encodes a 77kDa outer membrane
      protein. irgA expression is activated by irgB, which encodes a LysR-type
      transcription factor and is divergently transcribed from a promoter overlapping
      that of irgA. Expression of irgA and irgB is repressed by iron and Fur. A 200bp
      DNA fragment containing the irgA-irgB intergenic region was inserted between the
      Escherichia coli phoA and lacZ genes, respectively, to generate operon fusions to
      the two promoters, and this construct was crossed into the chromosomal lacZ gene
      of V. cholerae. This DNA fragment was sufficient to produce regulation of irgA
      phoA and irgB-lacZ transcription by iron, Fur and IrgB. Purified V. cholerae Fur
      and IrgB overexpressed in E. coli bound simultaneously to this DNA fragment in
      gel shift experiments, and footprints of both proteins on the irgA-irgB
      intergenic region were observed using DNaseI footprinting. The Fur footprint
      overlapped a Fur box, previously identified by homology with the E. coli Fur box.
      The position of the IrgB footprint was consistent with activation of irgA
      transcription and repression of irgB transcription by IrgB. We present a model
      for the interaction of Fur and IrgB in transcriptional regulation of irgA.

PMID- 9524226
TI  - Cloning of a novel human ELF-1-related ETS transcription factor, ELFR, its
      characterization and chromosomal assignment relative to ELF-1.
AB  - The ETS gene family encodes a group of proteins that function as transcription
      factors under physiological conditions and, if aberrantly expressed, can lead to
      cellular transformation. ETS transcription factors are characterized by a unique
      conserved DNA binding domain. A subset of these proteins is rearranged with EWS
      in Ewing tumors (ET). We recently described a spectrum of ETS genes coexpressed
      with EWS-FLI1 in an ETcell line to define proteins that potentially compete in
      target site selection. We now report on the cloning and characterization of a
      novel ETS family member, ELFR, displaying 92% homology to ELF-1 in its DNA
      binding domain while diverging in the rest of the protein. ELFR expression was
      found in a very tissue restricted pattern with the highest abundancy in placenta.
      We also report the chromosomal assignment of ELFR and ELF-1 to Xq26 and 13q13,
      respectively, by means of fluorescence in-situ hybridization (FISH).

PMID- 9524227
TI  - sn-Glycerol-3-phosphate dehydrogenase in the honey bee Apis mellifera -an unusual
      phenotype associated with the loss of introns.
AB  - In comparison with the numerous Drosophila species and the mouse, the Gpdh gene
      in the honey bee Apis mellifera lacks most introns. This prevents the gene from
      producing different GPDH isoforms by alternative splicing, which occurs in
      Drosophila melanogaster. The sequences of the cDNA and genomic Gpdh of A.
      mellifera are described and show that at the amino acid level they share 84%
      similarity and 71% identity with D. melanogaster. The identity at the nucleotide
      level is 62% in the coding region, but no significant similarities were detected
      in the UTRs. Northern analyses revealed an accumulation of unspliced Gpdh pre
      mRNA in the honey bee, probably reflecting splicing inefficiency, although it is
      also possible that splicing is a regulated step in Gpdh expression in A.
      mellifera. It is suggested that the intron loss occurred via reverse
      transcription of a mature Gpdh transcript.

PMID- 9524228
TI  - Analysis of the murine Hoxa-9 cDNA: an alternatively spliced transcript encodes a
      truncated protein lacking the homeodomain.
AB  - Hoxa-9 is one of the homeo box (Hox) genes exhibiting similarity to the
      Drosophila Abdominal B gene. So far, only partial nucleotide sequences have been
      reported for mouse Hoxa-9 cDNA (Rubin et al., (1987) Mol. Cell. Biol. 7, 3836
      3841). Here, we have determined the nucleotide sequence of the 5'-region of mouse
      Hoxa-9 cDNA and its genomic structure. Mouse Hoxa-9 cDNA contains a complete ORF
      encoding a protein of 271aa exhibiting 96.7% identity to its human counterpart.
      Interestingly, an alternatively spliced transcript (Hoxa-9T) was identified by RT
      PCR. Sequence analysis revealed that 173bp within the Hoxa-9 ORF was missing from
      the Hoxa-9T cDNA. This additional splicing would potentially result in a
      frameshift, leading to the production of a truncated protein lacking the
      homeobox. Northern blot analysis revealed that the probe containing the
      homeodomain hybridized to two major transcripts (2.5 and 1.9kb) in the trunk
      region of 12.5 dpc embryos, and adult kidney and large intestine. On the other
      hand, the probe containing the additional intron detected only 2.5kb transcript
      in the same tissues, indicating that 1.9kb transcript corresponds to Hoxa-9T
      mRNA. We have also determined the transcriptional start site of Hoxa-9T.

PMID- 9524229
TI  - Identification of a Cryphonectria parasitica laccase gene promoter element
      involved in cycloheximide-inducible, hypovirus-repressible transcriptional
      activation.
AB  - The gene lac-1, encoding the enzyme laccase, is the best characterized of a
      number of genes in the chestnut blight fungus, Cryphonectria parasitica, that are
      repressed by hypoviruses, a group of virulence-attenuating mycoviruses. lac-1 has
      also been shown to be transcriptionally activated by low concentrations of the
      translational inhibitor cycloheximide (CHX) and by the immunosuppressant
      cyclosporin A. We now report the identification of a CHX responsive element
      within the lac-1 promoter region. Gel-mobility shift analysis revealed a 111-bp
      fragment located 1.8kb upstream of the lac-1 transcriptional start point that
      exhibited protein binding activity. Insertion of this element within a basal lac
      1 promoter sequence conferred CHX responsive transcriptional activation.
      Moreover, this activation was prevented by hypovirus infection. A 22-bp sequence
      with an imperfect dyad symmetry located within the 111-bp element was found to be
      essential for sequence-specific protein binding and, thus, represents a putative
      target for interactions between the lac-1 promoter and proteins that are involved
      in mediating CHX inducible activation of lac-1 transcription.

PMID- 9524230
TI  - A topA intein in Pyrococcus furiosus and its relatedness to the r-gyr intein of
      Methanococcus jannaschii.
AB  - A new intein coding sequence was found in a topA (DNA topoisomerase I) gene by
      cloning and sequencing this gene from the hyperthermophilic Archaeon Pyrococcus
      furiosus. The predicted Pfu topA intein sequence is 373 amino acids long and
      located two residues away from the catalytic tyrosine of the topoisomerase. It
      contains putative intein sequence blocks (C, E, and H) associated with intein
      endonuclease activity, in addition to intein sequence blocks (A, B, F, and G)
      that are necessary for protein splicing. This DNA topoisomerase I intein is most
      related to a reverse gyrase intein from the methanogenic Archaeon Methanococcus
      jannaschii. These two inteins share 31% amino acid sequence identity and, more
      importantly, have the same insertion sites in their respective host proteins. It
      is suggested that these two inteins are homologous inteins present in
      structurally related, but functionally distinct, proteins, with implications on
      intein evolution and intein homing.

PMID- 9524231
TI  - Molecular cloning of a cDNA encoding a serine protease homologous to complement
      C1s precursor from rat C6 glial cells and its expression during glial
      differentiation.
AB  - A cDNA of rat C6 cells was cloned, which was considered to be involved in glial
      cell differentiation induced by dibutyryl cyclic AMP and theophylline. The cDNA
      fragment of the gene, termed r-gsp, was originally isolated by mRNA
      fingerprinting using arbitrarily primed polymerase chain reaction, and was
      homologous to complement C1s precursors of hamster and human. It encodes a
      protein of 694 amino acids containing a potential signal peptide, an epidermal
      growth factor-like domain surrounded by two complement C1r/C1s-related repeats,
      and a putative trypsin-type serine protease domain. Since the hamster and human
      C1s, and a protein encoded by r-gsp shared high similarity in primary structure,
      the r-gsp gene could encode a C1s counterpart of the rat. Messenger RNA
      expression of this gene was markedly increased during cyclic AMP-induced glial
      cell differentiation. Its expression profile was well correlated with those of
      glial fibrillary acidic protein (GFAP) and S100B, which are known as glial
      differentiation markers. It was, moreover, observed that the r-gsp expression in
      brain increased considerably after birth, like those of S100B and GFAP. The
      results presented here suggest that the rat C1s gene would be also implicated in
      glial differentiation besides the complement cascade.

PMID- 9524232
TI  - Involvement of phosphorylation in binding of nuclear scaffold proteins from rat
      liver to a highly repetitive DNA component.
AB  - The results of our previous work [Hibino et al., Biochim. Biophys. Acta 1174
      (1993) 162-170] suggested that a highly repetitive DNA component facilitates
      bending of the helix axis to be recognized by the nuclear scaffold proteins from
      rat liver, P123 and P130. In the present experiment, it was shown that binding of
      these proteins to such a repetitive DNA component from rat liver nuclei (370-bp
      XmnI fragment) is based on a cooperative mode of interaction, although the
      binding activity of P130 is much higher than that of P123. The immunoblot
      analysis with anti-phosphoamino acid antibodies suggested that phosphorylation of
      serine and threonine residues occurs on P123 and P130, but also of tyrosine
      residue(s) on P130. The phosphatase assay showed that phosphoryl groups on these
      proteins may be involved in altering the DNA binding activities of the proteins.
      Thus, the results in the present study imply that phosphorylation of a nuclear
      scaffold protein in addition to the degree of bending of the DNA helix axis plays
      an important role in anchoring chromatin to the nuclear scaffold and in
      construction of a higher-order chromatin structure.

PMID- 9524234
TI  - Spontaneous cAMP-dependent derepression of gene expression in stationary phase
      plays a role in recombinant expression instability.
AB  - E. coli recombinant expression systems that utilize lac operon control elements
      to modulate gene expression are known to produce some amount of uninduced (leaky)
      gene expression. Previously, we showed that high levels of uninduced gene
      expression was a major cause of instability in the pET expression system. We show
      here that the pET system, in which the phage T7 RNA polymerase gene is expressed
      via lac operon control elements, exhibits leaky expression that increases
      markedly as cells grown in complex medium enter stationary phase. Moreover, we
      found that this phenomenon occurs with the chromosomal lac operon as well.
      Further investigation revealed that stationary phase leaky expression requires
      cyclic AMP, and that substantial leaky expression could be effected in log phase
      cells by adding cyclic AMP and acetate at pH6.0. Finally, a comparison of
      otherwise isogenic cya and wild-type hosts showed that expression stability and
      plasmid maintenance in the cya host is greatly enhanced, even when cells are
      passaged repeatedly in non-selection medium. These findings both provide a method
      to enhance the stability of lac-based recombinant expression systems, and suggest
      that derepression of the lac operon in the absence of inducer may be part of a
      general cellular response to nutrient limitation.

PMID- 9524233
TI  - Chromosomal sequencing using a PCR-based biotin-capture method allowed isolation
      of the complete gene for the outer membrane protein A of Klebsiella pneumoniae.
AB  - By employing a novel biotin- and PCR-assisted capture method, which allows
      determination of unknown sequences on chromosomal DNA, the gene for the outer
      membrane protein A (OmpA) of Klebsiella pneumoniae has been isolated and
      sequenced to completion. The method involves linear amplification of DNA from a
      biotinylated primer annealing to a region with known sequence. After capture of
      the amplified single-stranded DNA on to paramagnetic beads, unspecifically
      annealing primers, i.e. arbitrary primers, were used to generate sequences with
      only partly determined nt sequences. The homology of the sequenced gene to ompA
      of related bacteria is discussed, and the gene fragment was assembled for
      intracellular expression in Escherichia coli, and two different fusion proteins
      were produced and recovered with good yields. The importance of the novel
      chromosomal sequencing method for gene isolation in general and the potential use
      of the OmpA fusion proteins are discussed.

PMID- 9524235
TI  - Identification of 10Sa RNA (tmRNA) homologues from the cyanobacterium
      Synechococcus sp. strain PCC6301 and related organisms.
AB  - We have isolated the 10Sa RNA (tmRNA) from the unicellular cyanobacterium
      Synechococcus sp. strain PCC6301. It comprises of 394 nucleotides (nt) and has
      55% homology to Escherichia coli tmRNA. The cloning and sequencing of the
      corresponding gene have revealed that, like in many tRNA genes, the terminal CCA
      sequence reported in all the tmRNA species characterized so far is not encoded in
      the DNA. Hybridization analysis has shown that the tmRNA gene is present as a
      single copy. Fairly high levels of tmRNA accumulate throughout the cell cycle;
      however, a slight increase in its level is observed during late-log to stationary
      phase. This suggests that tmRNA is functional not only when cells divide actively
      but also when cell growth stops.

PMID- 9524236
TI  - Improved differential screening approach to analyse transcriptional variations in
      organized cDNA libraries.
AB  - A cDNA library was generated from rat brain tissues and organized into 1536-well
      plates, using a fluorescence activated cell sorter (FACS), acting as a single
      cell deposition system. The organized library containing 10,000 clones, with 60%
      full-length cDNA inserts, allowed the generation of multiple identical membrane
      replicas. Each replica was hybridized with a complex probe obtained from a
      particular brain tissue or a given cultured cell. The signal intensity for each
      of the clones present on the membrane, quantified with a standard image-analysis
      software, is proportional both to the abundance of the corresponding mRNA in the
      probe and to the amount of plasmid template on the membrane. The latter value was
      thus used to normalize the signals produced with complex probes, to optimize the
      comparison of mRNA expression levels for the different systems under study. The
      construction of high-quality cDNA libraries, the generation of identical membrane
      replicas and comparable probes, and the utilization of an image-analysis software
      package, coupled with the normalization of the spot intensity by assaying plasmid
      quantity, significantly improves the differential screening approach. Altogether,
      these technical improvements open the possibility to compare a great number of
      different probes and, in consequence, to accumulate biological information for
      each clone present in an organized cDNA library. The functional information
      obtained should complement data from DNA sequencing projects.

PMID- 9524237
TI  - Cloning and expression of caprine interferon-gamma.
AB  - Caprine interferon-gamma (IFN-gamma) cDNA was cloned from mitogen stimulated
      peripheral blood mononuclear cell (PBMC) RNA utilizing the reverse transcription
      polymerase chain reaction (RT-PCR). The cDNA open reading frame (ORF) is 498bp,
      encoding a putative 166 amino acid (aa) protein (19327Da). The predicted aa
      sequence homology of caprine IFN-gamma and the corresponding ovine, bovine and
      cervine cytokine is 98.8%, 95.2% and 92.8%, respectively. IFN-gamma cDNA was
      subcloned and expressed in two different plasmids under the control of either the
      human cytomegalovirus (CMV) immediate early promoter or the caprine arthritis
      encephalitis virus long terminal repeat (CAEV LTR). Recombinant caprine IFN-gamma
      (rCaIFN-gamma) secreted by transfected COS-7 cells shared at least two antigenic
      epitopes with recombinant bovine IFN-gamma (rBoIFN-gamma) and exhibited
      biological activity in the vesicular stomatitis virus (VSV) cytopathic effect
      reduction assay. In-vivo expression of IFN-gamma cDNA promoted by the CAEV LTR
      was confirmed by the intramuscular (IM) injection of Balb/C mice with plasmid
      followed by Western blot analysis of mouse serum against purified rCaIFN-gamma
      produced in E. coli.

PMID- 9524238
TI  - Molecular cloning of human and bovine LECT2 having a neutrophil chemotactic
      activity and its specific expression in the liver.
AB  - We previously reported the purification and amino acid sequence of a novel
      neutrophil chemotactic protein termed LECT2 (leukocyte cell-derived chemotaxin
      2). In this paper we report molecular cloning of human and bovine LECT2 cDNAs
      based on the amino acid sequence of the purified protein. The deduced amino acid
      sequence of human LECT2 (hLECT2) shows an 86% identity to bovine LECT2 (bLECT2).
      The deduced primary structures of LECT2 were highly homologous to the repeated
      units of Mim-1 protein (myb induced myeloid protein-1). The mim-1 gene is one of
      the known myb target genes and is specifically expressed in normal and
      transformed immature granulocytes in the chicken. Northern blot analysis of
      normal human tissues demonstrated that the hLECT2 gene is specifically expressed
      in the adult and fetal livers. In addition, several human hepatoma cell lines
      also expressed LECT2 mRNA, suggesting that hepatic cells in the liver produce
      LECT2 protein.

PMID- 9524239
TI  - Molecular cloning and characterization of two phosphatase 2A catalytic subunit
      genes from Arabidopsis thaliana.
AB  - The plant Arabidopsis thaliana contains five isoforms of the catalytic subunit of
      protein phosphatase 2A (PP2A) that can be grouped into two families, one composed
      by isoforms PP2A-1, -2 and -5 and the other composed by isoforms PP2A-3 and PP2A
      4. An Arabidopsis genomic library was screened and several clones corresponding
      to genes PP2A-3 and PP2A-4 were isolated and analysed. Both genes span over
      approximately 4.5kbp and are composed of 11 exons and 10 introns that show
      identical organization. Their untranslated regions are also highly conserved,
      suggesting that the two genes derive from a common ancestral gene. However, the
      position of intron/exon junctions completely differs from that of the human PP2A
      genes. Two transcription start sites have been found in the PP2A-3 gene, the
      major one mapping at nucleotide position -188 from the translation start codon,
      whereas only one is observed in PP2A-4 (-145). Functional gene promoter analysis
      reveals that elements required for transient expression of PP2A-3 and PP2A-4 on a
      protoplast system are contained within a region of about 600bp upstream from the
      transcription start sites. This is the first report on the cloning and
      characterization of genes encoding catalytic subunits of Ser/Thr protein
      phosphatases 2A in higher plants.

PMID- 9524240
TI  - Molecular approaches for production of pravastatin, a HMG-CoA reductase
      inhibitor: transcriptional regulation of the cytochrome p450sca gene from
      Streptomyces carbophilus by ML-236B sodium salt and phenobarbital.
AB  - We have characterized the transcriptional regulation of ML-236B.Na and
      phenobarbital-inducible cytochrome P450sca-2 (CytP450sca-2) from Streptomyces
      carbophilus, an industrial pravastatin-producing strain. ML-236B.Na and
      phenobarbital enhanced the expression of the cytP450sca-2 gene in S. carbophilus.
      The cytP450sca-2 gene was also ML-236B.Na-inductive in S. lividans. Analysis of
      various deletion and mutation of the 5'-flanking region of the cytP450sca-2 gene
      revealed that the 1-kb region was required for ML-236B.Na-dependent CytP450sca-2
      induction. We have found a putative ORF in the 5'-flanking region that encodes a
      protein of 174 amino acid residues containing a helix-turn-helix DNA-binding
      motif. A gel mobility shift assay showed that the protein was bound by an
      imperfect palindromic sequence between -46bp and -24bp in the 5'-flanking region,
      and ML-236B.Na was found to inhibit its binding. These findings suggest that
      induction of cytP450sca-2 is negatively regulated at the transcriptional level
      and that the protein encoded by the putative ORF is possibly functional as a
      repressor of the cytP450sca-2 gene.

PMID- 9524241
TI  - Multiple promoters are responsible for transcription of the glpEGR operon of
      Escherichia coli K-12.
AB  - The transcriptional organization of the glpEGR genes of Escherichia coli was
      studied. Besides a promoter located upstream of the glpE start codon, three
      internal glpGR promoters were identified that express glpG and/or glpR (glp
      repressor). One promoter was located just upstream of the glpG start codon and
      two others (separated by several hundred base pairs) were located within glpG
      upstream of the glpR start codon. The transcriptional start points of these
      promoters were identified by primer extension analysis. The strengths of the
      individual promoters were compared by analysis of their expression when fused to
      a pormoter-probe vector. Analysis of the transcriptional expression of the glpEGR
      sequence with different combinations of the glpEGR promoters revealed no internal
      transcriptional terminators within the entire operon. Thus, the glpEGR genes are
      co-transcribed and form a single complex operon. The presence of multiple
      promoters may provide for differential expression of glpE, glpG and glpR.
      Potential regulation of the operon promoters by GlpR, catabolite repression,
      anaerobiosis or by FIS was studied. The glpE promoter was apparently controlled
      by the cAMP-CRP complex, but none of the promoters was responsive to specific
      repression by GlpR, to anaerobiosis or to FIS. Specific repression exerted by
      GlpR was characterized in vivo using glpD-lacZ and glpK-lacZ fusions. The degree
      of repression was correlated with the level of GlpR expression, and was
      inefficient when the glpD-encoded glycerol-P dehydrogenase was absent, presumably
      due to accumulation of the inducer, glycerol-P. This is in contrast to the
      previous conclusion that gpsA-encoded glycerol-P synthase tightly controls the
      cellular level of glycerol-P by end product inhibition.

PMID- 9524242
TI  - Cloning and expression of Staphylococcus aureus and Treptococcus pyogenes murD
      genes encoding uridine diphosphate N-acetylmuramoyl-L-alanine:D-glutamate
      ligases.
AB  - Bacterial UDP-N-acetylmuramyl-L-alanine:D-glutamate ligase (MurD), a cytoplasmic
      peptidoglycan biosynthetic enzyme, catalyzes the ATP-dependent addition of D
      glutamate to an alanyl residue of the UDP-N-acetylmuramyl-L-alanine precursor,
      generating the dipeptide. The murD gene was cloned from both Staphylococcus
      aureus and Streptococcus pyogenes. Sequence analysis of the S. aureus murD gene
      revealed an open reading frame of 449 amino acids. The deduced aa sequence of S.
      aureus MurD is highly homologous to MurD from Escherichia coli, Haemophilus
      influenzae, Bacillus subtilis and St. pyogenes. Recombinant MurD protein from
      both S. aureus and St. pyogenes was separately overproduced in E. coli and
      purified as His-tagged fusion. Both recombinant enzymes catalyzed the ATP
      dependent addition of D-glutamate to the precursor sugar peptide.

PMID- 9524243
TI  - Further characterization of the murine collagenase (type IVB) gene promoter and
      analysis of mRNA expression in murine tissues.
AB  - The collagenase B type IV (Col4B) gene is highly expressed in the osteoclast, the
      primary bone-resorbing cell. However, factors that regulate expression of the
      Col4B gene are not well characterized. A murine P1 genomic clone containing a 94
      kb sequence insert which contains the Col4B gene was isolated. A 4 kb EcoR1 DNA
      fragment containing the 5' flanking sequence of the gene was further subcloned
      and restriction mapped. Putative transcription factors such as SRY, Lyf-1, and
      GATA1 and 2, binding motifs were identified by sequence analysis in this promoter
      region. Enhancer and suppressor regions were mapped by transient expression of
      Col4B gene promoter deletion mutant-luciferase reporter gene constructs in HepG2
      cells. Col4B mRNA expression in different murine tissues was analyzed by reverse
      transcription-polymerase chain reaction and demonstrated high levels of
      expression in bone, clavaria, spleen and thymus. This promoter provides a
      valuable tool for targeting gene expression to the osteoclast.

PMID- 9524244
TI  - Identification of a novel transcriptional silencer in the protein-coding region
      of the human CYP2C9 gene.
AB  - A novel regulatory element (27 bp) which confers transcriptional repression was
      identified within the protein-coding region immediately after the translation
      start codon in the human cytochrome P450 (CYP) 2C9 gene. Deletion of this element
      increased transcriptional activity in HepG2 cells by transient transfection
      assay. Nuclear protein extracts from HepG2 cells and human liver were found in
      electrophoretic mobility shift assays to bind specifically to the 27 bp element.
      A putative binding protein was partially purified by DNA-affinity chromatography
      and was determined by Southwestern blotting to have a molecular weight of approx.
      100 kDa. Studies with mutated competitor oligonucleotides established that
      binding of the nuclear protein to the 27 bp cis-element was dependent upon two 6
      bp direct repeats (5'-CTTGTG-3') that were separated by three bases. It is
      possible that this novel cis-acting element may be involved in the negative
      regulation of CYP2C9.

PMID- 9524245
TI  - Structure and hair follicle-specific expression of genes encoding the rat high
      sulfur protein B2 family.
AB  - High sulfur proteins are cysteine-rich proteins synthesized during the
      differentiation of hair matrix cells, and form hair fibers in association with
      hair keratin intermediate filaments. Rat high sulfur protein B2 genes were
      isolated after screening of a rat genomic library using the cDNA as a probe.
      Sequence analysis of a 4 kb fragment revealed two high sulfur protein genes, B2E
      and B2F. Both genes lacked introns, with B2F being located at 2 kb downstream of
      B2E. The 5' flanking regions of both genes had TATA and CAAT boxes, and consensus
      sequences of B2 genes. The upstream region of B2F had possible AP-1 and Sp-1
      binding elements. The high sulfur protein B2E and B2F, which have putative 188
      and 122 amino acids, respectively, comprised four distinct domains with a
      characteristic repetitive sequence. In situ hybridization indicated that the mRNA
      of high sulfur protein B2 was specifically localized in the cortex of the hair
      shaft, and northern blot analysis indicated that the expression of B2 increased
      in anagen and decreased in telogen, suggesting that high sulfur protein B2
      synthesized in cortical cells during anagen contributes to the production of hair
      fibers.

PMID- 9524247
TI  - Characterization of the sheep apolipoprotein E (ApoE) gene and allelic variations
      of the ApoE gene in scrapie Suffolk sheep.
AB  - Apolipoprotein E (ApoE) plays a central role in lipid transport and is suggested
      to be involved in neuronal repair. Human ApoE epsilon 4 allele is known as a risk
      factor for Alzheimer's disease, and an association of the human ApoE genotype
      with the human prion disease, Creutzfeldt-Jakob disease, is suggested, albeit
      controversial. We analyzed the sheep ApoE gene to determine whether any
      association between the sheep ApoE genotype and the sheep prion disease, scrapie,
      existed. The sheep ApoE cDNA contained an open reading frame (ORF) consisting of
      948 base pairs (bp) that encoded 316 amino acids (aa). The sheep ApoE gene was
      composed of four exons separated by three introns, and the ORF was encoded by
      three exons, designated exons 2, 3, and 4. Nucleotide sequence analysis also
      showed the presence of one G/T nucleotide polymorphism in the ORF that resulted
      in an Ala/Ser amino-acid substitution at codon 258. PCR-restriction fragment
      length polymorphism analysis of genomic DNA showed the presence of three sheep
      ApoE genotypes that were the result of the homologous and heterologous
      combinations of the two alleles. We analyzed the sheep ApoE genotypic and the
      allelic frequencies in scrapie and control Suffolk sheep, but they did not
      significantly differ from those in the control sheep, even though PrP genotype
      matched populations were compared. The ApoE genotype appeared not to be
      associated with the progression of the disease when looking at the age at death.
      These results indicated that in Suffolk sheep, none of the ApoE genotypes was
      associated with scrapie.

PMID- 9524246
TI  - XL43 and XL75: two novel RING finger-containing genes expressed during oogenesis
      and embryogenesis in Xenopus laevis.
AB  - This article reports on the isolation of two new Xenopus genes that encode two
      putative zinc finger proteins. The XL43 and XL75 proteins belong to the RBCC
      family, and also contains the rfp-like domain. XL43 and XL75 RNAs are found in
      the ovary, and myc-tagged proteins are detected in mRNA injected oocytes. Whole
      mount in situ hybridization of embryos revealed that these two clones are
      expressed exclusively in neurectodermic and mesodermic tissues. The data suggest
      that XL43 and XL75 genes could play an important role in the frog's early
      development, perhaps as a transcription factor. This RBCC family, a subclass of
      the RING finger family, comprises proteins with known cellular transformation
      properties. All members possess, besides one RING finger motif, one or two B
      boxes, each having a pair of zinc fingers, and a coiled coil domain (Borden, K.L.
      B. et al., 1996. Proc. Natl. Acad. Sci. USA 93, 1601-1606). Among this group,
      some members possess, besides the RING-B box-coiled coil (RBCC) motifs, a long C
      terminal domain referred to as the rfp-like domain. Although its effective role
      has not been elucidated yet, this last domain could play an important role by
      binding a ligand (Bellini, M. et al., 1993. EMBO J. 12, 107-114).

PMID- 9524248
TI  - The largest subunit of mouse RNA polymerase II (RPB1) functionally substituted
      for its yeast counterpart in vivo.
AB  - The full-length mouse RNA polymerase II (pol II) largest subunit (RPB1) gene was
      used to replace 5070 bp of the yeast Saccharomyces cerevisiae RPB1 gene via
      homologous recombination and gene replacement in vivo. Transcription of the mouse
      RPB1 gene using the yeast promoter in the haploid state was confirmed by Northern
      analysis. This strain of yeast is viable, indicating that mouse RPB1 is able to
      interact functionally with the other yeast RNA pol II subunits in vivo.

PMID- 9524249
TI  - Translationally repressive RNA structures monitored in vivo using temperate DNA
      bacteriophages.
AB  - The RNA challenge phage system enables genetic selection of proteins with RNA
      binding activity in bacteria. These phages are modified versions of the temperate
      DNA bacteriophage P22 in which post-transcriptional regulatory events control the
      developmental fate of the phage. The system was originally developed to identify
      novel RNA ligands that display reduced affinity for the R17/MS2 coat protein, as
      well as to select for suppressor coat proteins that recognize mutant RNA ligands.
      During the course of evaluating whether the HIV-1 Rev protein could direct
      lysogen development for bacteriophage derivatives that encode Rev response
      element (RRE) RNA sequences, two examples of RRE RNA ligands that interfere with
      challenge phage development were identified. In the phage examples described, RRE
      RNA secondary structure prevents Ant protein biosynthesis and lytic development.
      Phage lysogen formation occurs efficiently in recipient cells, independent of the
      expression status of the Rev protein or trans-acting competitor RRE RNA ligands.
      These studies provide the first example whereby RNA challenge phages may be
      applied to study RNA folding events and RNA structural interactions in an in vivo
      context.

PMID- 9524250
TI  - Gap junction Cx26 gene modulation by phorbol esters in benign and malignant human
      mammary cells.
AB  - Connexin (Cx) 26, a major gap junction protein expressed in mammary epithelial
      cells, has been considered to be a tumor suppressor gene candidate. This study
      investigated the molecular mechanism of transcriptional up-regulation of Cx26 by
      phorbol ester (TPA) in human immortalized MCF-10 mammary epithelial cells and MDA
      MB-231 mammary cancer cells. Such up-regulation was mediated through the protein
      kinase C pathway and could be blocked by the PKC inhibitor, calphostin C. Based
      on the results of the nuclear run-on assay, there was a TPA-induced increase in
      the rate of transcriptional initiation. We identified a TPA-induced DNase I
      hypersensitivity (DH) region approximately 1 kb 5' upstream of the ATG
      translation starting site. Sequence analysis revealed that this DH region was
      located in intron 1 and contained two TRE-like TGAT/ATCA elements, two 5'TTCA3'
      motifs and a 5'AGGAAG3' PEA3 motif. Both TRE-like elements were capable of
      binding AP1. TPA inducibility of this DH region was seen by the CAT reporter
      assay and appeared to be direction-dependent suggesting a functional cooperation
      between PEA3/TTCA and TRE.

PMID- 9524251
TI  - Gene organization and chromosome location of the neural-specific RNA binding
      protein Elavl4.
AB  - We have isolated the gene that encodes the neural-specific RNA binding protein
      HuD in the mouse (Elavl4), and have mapped its location to the mid-distal region
      of chromosome 4, close to the neurological mutant clasper. The coding region of
      the Elavl4 gene covers approximately 44 kb; the first two RNA binding domains
      (RBDs) that are homologous to the two RBDs found in the Drosophila sex-lethal
      gene are each encoded in two exons, whereas the third RBD is encoded in a single
      exon. Elavl4 mRNAs are alternatively spliced in the region between RBDs 2 and 3
      due to the variable use of two micro-exons, and RNase protection analysis
      indicates that two of four possible splice variants are the predominant isoforms
      expressed in the central nervous system. The high degree of sequence conservation
      between the Hu proteins suggests that the exon organization of all the Hu protein
      genes will be similar, if not identical, to the Elavl4 gene.

PMID- 9524252
TI  - Isolation of a novel heat shock protein 70-like gene, pss1+ of
      Schizosaccharomyces pombe homologous to hsp110/SSE subfamily.
AB  - A novel heat shock protein 70 (HSP70) gene, pss1+, of fission yeast,
      Schizosaccharomyces pombe (S. pombe), has been isolated as a multicopy suppressor
      of a synthetic lethal mutant of ras1+, which shows severe retardation of growth
      and aggregation phenotype when the ras1 gene function is absent. The pss1+ gene
      functionally complements the growth defect of the mutant. Sequence analysis
      revealed that pss1+ encodes an open reading frame (ORF) of 730amino acids that is
      homologous to the HSP70 family proteins. The Pss1 has high homology to the
      Saccharomyces cerevisiae (S. cerevisiae) heat shock protein Sse1p/Msi3p (43%
      identity) that belongs to the HSP110/SSE subfamily of HSP70. The consensus
      nucleotide sequence of the heat shock element (HSE) was found in the upstream
      region of pss1+ gene. The transcript level of pss1+ was moderately abundant
      during steady-state growth at 25 degrees C and increased a few-fold upon shifting
      to 42 degrees C. Furthermore, transcription of pss1+ increased in nitrogen
      starved conditions. Disruption of the pss1+ gene confers a temperature-sensitive
      growth phenotype and unexpectedly causes the increase in thermotolerance in S.
      pombe.

PMID- 9524253
TI  - 22-Mb integrated physical and genetic map based on YAC/STS content spanning the
      interval DXS1125-DXS95 in human Xq12-q21.31.
AB  - A YAC/STS map has been assembled spanning 22 Mb across Xq12-q21.31, between
      markers DXS1125 and DXS95. In addition to the landmark loci for the X
      inactivation center XIST and the ATRX, ATP7A, phosphoglycerate kinase, POU3F4,
      and choroideremia genes, the candidate disease gene regions for torsion dystonia
      3 and two X-linked mental retardation syndromes are included. Also, the human
      voltage-dependent anion channel gene (HVDAC1) has been placed near DXS986. The
      current map incorporates 211 YACs from five different libraries, formatted with
      185 STSs that comprise 26 genetic linkage markers, 60 newly-developed YAC-end
      STSs, and eight ESTs. The multiple clone coverage and average resolution of one
      STS per 120 kb provide resources for disease gene searches and are facilitating
      complete sequencing of the region.

PMID- 9524254
TI  - cDNA cloning and expression analysis of the murine ribonuclease L inhibitor.
AB  - The 2-5A/RNase L system is one of the pathways induced by interferon (IFN). It
      plays a major role in the antiviral and antiproliferative activities of IFNs.
      Recently, we have shown that the activity of the RNase L could be inhibited by a
      proteic inhibitor, the RNase L Inhibitor (RLI). Human RLI (Hu-RLI) was cloned and
      characterized. We describe here the isolation and characterization of the cDNA
      encoding the murine RLI (Mu-RLI). Hu-RLI and Mu-RLI protein have 98% amino acid
      identity. Mu-RLI is functionally homologous to Hu-RLI, and all the structural
      features and amino acid sequence motifs of Hu-RLI are conserved in Mu-RLI.
      Moreover, reticulocyte lysate translated Mu-RLI protein is also able to inhibit 2
      5A binding on 2-5A-dependent RNAse-L. Northern blot analysis revealed that Mu-RLI
      cDNA hybridizes with one mRNA of 3.5 kb except for the testis where two mRNA of
      3.5 and 2.1 kb, respectively, are detected, suggesting a tissue-specific
      regulation.

PMID- 9524255
TI  - Topoisomerase I of Helicobacter pylori: juxtaposition with a flagellin gene
      (flaB) and functional requirement of a fourth zinc finger motif.
AB  - Cloning and nucleotide sequence analysis showed that in Helicobacter pylori the
      gene encoding topoisomerase I (topA) lies about 170 nucleotides upstream from
      flaB, a gene encoding one of the two flagellin proteins that is required for
      virulence. The topA and flaB genes are divergently transcribed. The orientation
      and spatial relationship between flaB and topA are remarkably conserved among
      strains of a bacterium in which genomic rearrangements are common. The deduced
      amino acid sequence of topoisomerase I revealed four zinc finger motifs, one more
      than has been reported previously for the Escherichia coli homologue. The
      additional motif, which is near the C-terminus of the protein, appears to be
      essential for function since mutations in that region are lethal. These data show
      that TopA proteins can be divided into several classes on the basis of zinc
      finger motifs and raise the interesting possibility that the H. pylori enzyme has
      local topological effects focussed on a flagellin gene.

PMID- 9524257
TI  - A new yeast artificial chromosome vector designed for gene transfer into
      mammalian cells.
AB  - This report describes the construction of a new yeast artificial chromosome (YAC)
      vector designed for gene transfer into mammalian cells. For ease of use, the two
      arms of the vector were cloned separately. The vector harbours the Neo and Hyg
      genes for dominant selection in mammalian cells, a putative human origin of
      replication, a synthetic matrix attachment region and two loxP sites (one on each
      arm). The cloning ability of the vector was demonstrated by successful
      propagation of the cDNA of the cystic fibrosis gene, CFTR, as a YAC in
      Saccharomyces cerevisiae. A YAC containing the entire CFTR gene was also
      constructed by retrofitting the two arms of a pre-existing clone (37AB12) with
      the two arms of the novel vector. Both the cDNA and entire gene containing YACs
      were circularized in yeast by inducible expression of the Cre recombinase.
      Recombination occurred very specifically at the loxP sequences present on the two
      arms of the YAC. Applications of the vector to gene transfer are discussed.

PMID- 9524256
TI  - A novel 52 kDa protein induces apoptosis and concurrently activates c-Jun N
      terminal kinase 1 (JNK1) in mouse C3H10T1/2 fibroblasts.
AB  - A 52 kDa protein (p52) was purified from chicken embryos and its corresponding
      cDNA was cloned. The p52 cDNA is 1768 bp long and has an open reading frame of
      465 amino acids. The sequence of the p52 cDNA shows significant homology with
      mouse and human cDNAs from the EST database, so do the deduced amino acid
      sequences, indicating the existence of human and mouse homologues of p52.
      Northern blot hybridization showed that the p52 mRNA was expressed in a wide
      range of embryonic and adult tissues. There was more p52 mRNA in embryonic heart
      and liver than in the brain or muscle. The adult testis had the highest level of
      p52 mRNA, whereas adult liver had the lowest. Expression of p52 in mouse
      C3H10T1/2 fibroblasts caused apoptotic cell death, upregulation of transcription
      factor c-Jun and activation of c-Jun N-terminal kinase 1 (JNK1). In addition,
      expression of Bcl-2, but not of the dominant negative mutant JNK1, can block the
      p52-mediated apoptosis. These results indicate that p52 may represent a new cell
      death protein inducing apoptosis and activating JNK1 through different pathways.

PMID- 9524258
TI  - Corrigendum to: 'Sequence, molecular organization and products of the drosophila
      virilis homologs of the D. melanogaster nested genes lethal(2) tumorous imaginal
      discs

PMID- 9524259
TI  - Cloning of human p55 gamma, a regulatory subunit of phosphatidylinositol 3
      kinase, by a yeast two-hybrid library screen with the insulin-like growth factor
      I receptor.
AB  - We have used the yeast two-hybrid system to identify proteins that interact with
      the intracellular domain of the insulin-like growth factor-I receptor (IGFIR). In
      a search of a human fetal brain library we identified a cDNA encoding a protein
      that is the human homologue of mouse p55PIK, a regulatory subunit of
      phosphatidylinositol 3-kinase (hp55 gamma). The hp55 gamma protein interacts
      strongly with the activated IGFIR but not with the kinase-negative mutant
      receptor. hp55 gamma also interacts with the insulin receptor (IR) in the yeast
      two-hybrid system. The putative hp55 gamma protein is composed of a unique amino
      terminal region followed by a proline-rich motif and two Src homology 2 (SH2)
      domains, which are highly homologous to those in mouse p55PIK, rat p55 gamma,
      human p85 alpha and bovine p85 beta; it contains no SH3 domain. hp55 gamma mRNAs
      are expressed in most human fetal and adult tissues with particularly high
      abundance in adult testis. Splice variant(s) of hp55 gamma, one of which has a
      deletion of 36 amino acids at the amino terminus and another which has an
      insertion of 59 amino acids at position 256 between the SH2 domains, were also
      identified. A GST-hp55 gamma fusion protein interacts in vitro with both the
      activated IGFIR and IR derived from mammalian cells. Our findings suggest that
      hp55 gamma interacts with the IGFIR and IR and may be involved in PI 3-kinase
      activation by these receptors.

PMID- 9524260
TI  - Cloning and sequence analysis of the plasmid-borne genes encoding the Eco29kI
      restriction and modification enzymes.
AB  - The Eco29kI restriction-modification system (RMS2) has been found to be localized
      on the plasmid pECO29 occurring naturally in the Escherichia coli strain 29k
      (Pertzev, A.V., Ruban, N.M., Zakharova, M.V., Beletskaya, I.V., Petrov, S.I.,
      Kravetz, A.N., Solonin, A.S., 1992. Eco29kI, a novel plasmid encoded restriction
      endonuclease from Escherichia coli. Nucleic Acids Res. 20, 1991). The genes
      coding for this RMS2, a SacII isoschizomer recognizing the sequence CCGCGG have
      been cloned in Escherichia coli K802 and sequenced. The DNA sequence predicts the
      restriction endonuclease (ENase) of 214 amino acids (aa) (24,556 Da) and the DNA
      methyltransferase (MTase) of 382 aa (43,007 Da) where the genes are separated by
      2 bp and arranged in tandem with eco29kIR preceding eco29kIM. The recombinant
      plasmid with eco29kIR produces a protein of expected size. MEco29kI contains all
      the conserved aa sequence motifs characteristic of m5C-MTases. Remarkably, its
      variable region exhibits a significant similarity to the part of the specific
      target-recognition domain (TRD) from MBssHII--multispecific m5C-MTase (Schumann,
      J.J., Walter, J., Willert, J., Wild, C., Koch D., Trautner, T.A., 1996. MBssHII:
      a multispecific cytosine-C5-DNA-methyltransferase with unusual target recognizing
      properties. J. Mol. Biol. 257, 949-959), which recognizes five different sites on
      DNA (HaeII, MluI, Cfr10I, SacII and BssHII), and the comparison of the nt
      sequences of its variable regions allowed us to determine the putative TRD of
      MEco29kI.

PMID- 9524261
TI  - Allelic retrieval: a scheme to facilitate the repeated isolation of a specific
      segment of the Bordetella pertussis chromosome.
AB  - A plasmid vector was designed, constructed, and used for the repeated retrieval
      of the bvgA gene from a number of Bordetella pertussis strains that, due to
      mutations in this gene, exhibited interesting phenotypes regarding the regulation
      of virulence genes. The vector was used in a scheme called allelic retrieval that
      exploits two cross-overs between cloned plasmid and native chromosomal sequences
      flanking the bvgA gene. This scheme is very similar to allelic exchange through
      the use of plasmid suicide vectors, but in the case presented here, the non
      replicating plasmid that has received the chromosomal gene is recovered, rather
      than being allowed to be lost due to segregation. Incorporation of the
      counterselectable sacB gene of Bacillus subtilis in place of the plasmid copy of
      bvgA allows selection, after recovery in Escherichia coli, for only those
      plasmids that have retrieved the chromosomal bvgA gene. The validity of this
      approach was demonstrated by the retrieval of bvgA alleles with distinctive
      physical markers, as well as by the reintroduction of retrieved bvgA alleles to
      demonstrate that they conferred the expected phenotypes. It is expected that this
      approach will be applicable to the analysis of other genes in other bacterial
      species.

PMID- 9524262
TI  - Cloning and analysis of the shiA gene, which encodes the shikimate transport
      system of escherichia coli K-12.
AB  - In Escherichia coli K-12, the shiA gene is involved in the uptake of shikimate.
      This gene has been cloned and its nucleotide sequence determined. The gene is
      predicted to encode a protein of 438 amino acids and lies adjacent to the amn
      gene. The hydropathy profile and the amino acid sequence indicate that the ShiA
      protein is a polytopic membrane protein that shows a homology with members of the
      major facilitator superfamily of transport proteins. Recombining an inactive form
      of the cloned gene into the chromosome creates mutants unable to transport
      shikimate. Introducing a wild-type gene on a multicopy plasmid into a shiA mutant
      restores the ability to transport shikimate. When this multicopy shiA plasmid is
      introduced into an aroE strain, this strain is now able to grow with shikimate as
      the aromatic supplement, consistent with the notion that dehydroshikimate (DHS)
      accumulated in an aroE strain prevents uptake of shikimate by competition.
      Expression of the shiA gene does not appear to be regulated by the TyrR protein,
      a repressor/activator that controls the expression of other genes involved with
      the biosynthesis or transport of the aromatic amino acids.

PMID- 9524263
TI  - Isolation and characterisation of smallminded, a Drosophila gene encoding a new
      member of the Cdc48p/VCP subfamily of AAA proteins.
AB  - Smallminded (smid) encodes a new member of the cdc48p/VCP subfamily of AAA
      proteins in Drosophila. The gene was isolated by plasmid rescue from a GAL4
      enhancer trap line which shows reporter gene expression in neuroblasts, imaginal
      disks and a subset of sensory neurons. Larvae homozygous for the insert arrest
      development as second instar larvae and die without pupating. The most obvious
      defect in these larvae is a significantly reduced CNS, hence the naming of the
      gene as smallminded. The deduced amino acid sequence of smid contains a tandem
      duplication of the AAA nucleotide binding domain characteristic of the cdc48p/VCP
      subfamily. Overall, smid shares 33% identical residues with its closest relative,
      yeast L0919-chrXII and 26-29% with other members of the cdc48p/VCP subfamily. The
      most highly conserved regions of the predicted protein structure are found in and
      around the nucleotide binding domains. The gene is expressed at all developmental
      stages.

PMID- 9524264
TI  - cDNA cloning of a novel rainbow trout SRY-type HMG box protein, rtSox23, and its
      functional analysis.
AB  - We have isolated a cDNA clone for a new member of Sox genes, termed rtSox23, from
      a rainbow trout ovary cDNA library. rtSox23 mRNA was notably expressed in ovary
      and brain. rtSox23 contains a leucine zipper in addition to an SRY-type HMG box.
      Although the recombinant HMG box region protein of rtSox23 could bind to an
      AACAAT sequence, the full-length rtSox23 could form a homodimer and did not bind
      to the sequence. Furthermore, using a two-hybrid system, we have isolated a cDNA
      clone encoding a protein that bound to the leucine zipper region of rtSox23. This
      protein was the rainbow trout homologue of mouse nucleoporin p62, which is a
      component of the nuclear pore complex in nuclear envelope. The rainbow trout p62
      mRNA was also prominent in ovary and brain. Taken together, these results suggest
      that the rainbow trout p62 associates with rtSox23 in vivo and modulates the
      function of rtSox23.

PMID- 9524265
TI  - Cloning and characterization of mouse mSox13 cDNA.
AB  - A novel SRY-related cDNA, mSox13, was isolated from a lambda phage library
      derived from mouse embryo. The cDNA encodes a protein of 595 amino acids
      containing the SRY-type high mobility group (HMG) box and a putative leucine
      zipper motif. A sequence comparison of mSox13 and other type-D SOX proteins shows
      that the leucine zipper and a neighboring glutamine-rich sequence stretch, which
      was named Q box, are well conserved among known type-D SOX proteins. The
      expression of mSox13 is restricted to the kidney and ovary. The electrophoretic
      mobility shift assay indicates that the recombinant mSox13 protein is capable of
      binding to the AACAAT sequence.

PMID- 9524266
TI  - Analysis of a 14-kb fragment containing a putative cell wall gene and a candidate
      for the ARA1, arabinose kinase, gene from chromosome IV of Arabidopsis thaliana.
AB  - An Arabidopsis thaliana genomic DNA fragment of 14kb has been characterized in
      the framework of the E.S.S.A. programme. Computational and molecular approaches
      identified three novel gene sequences coding, respectively, for a protein of
      unknown function, a putative membrane-anchored cell wall protein and an arabinose
      kinase gene corresponding to the locus ARA1. The latter two genes named AtSEB1
      and AtISA1 have been characterized in detail. They are very different in their
      organization, codon usage and level of expression. Homologues of AtSEB1 and
      AtISA1 have been identified. Sequence comparisons showed that the former genes
      contained a long 5' extension coding for an N-terminal domain probably specifying
      subcellular localization. Cloning and sequencing of the cognate cDNA for the
      AtISA1 homologue in A. thaliana, named GAL1, indicate that it encodes for a
      galactokinase-like protein. Our results highlight the integrative outcome of a
      systematic sequencing project in which links between biochemically and
      genetically characterized mutants, ESTs and genomic sequence data are generated.

PMID- 9524267
TI  - Cloning of a cDNA from Arabidopsis thaliana homologous to the human XPB gene.
AB  - The human gene XPB, defective in xeroderma pigmentosum patients complementation
      group B, encodes a DNA helicase involved in several DNA metabolic pathways,
      including DNA repair and transcription. The high conservation of this gene has
      allowed the cloning of homologs in various species, such as mouse, yeast and
      Drosophila. Not much information on the molecular basis of nucleotide excision
      repair in plants is available, but these organisms may have similar mechanisms to
      other eukaryotes. A homolog of XPB was isolated in Arabidopsis thaliana by using
      polymerase chain reaction (PCR) with degenerate oligonucleotides based on protein
      domains which are conserved among several species. Screening of an Arabidopsis
      cDNA library led to the identification and isolation of a cDNA clone with 2670 bp
      encoding a predicted protein of 767 amino acids, denoted araXPB. Genomic analysis
      indicated that this is a nuclear single copy gene in plant cells. Northern blot
      with the cDNA probe revealed a major transcript which migrated at approx. 2,800
      b, in agreement with the size of the cDNA isolated. The araXPB protein shares
      approximately 50% identical and 70% conserved amino acids with the yeast and
      human homologs. The plant protein maintains all the functional domains found in
      the other proteins, including nuclear localization signal, DNA-binding domain and
      helicase motifs, suggesting that it might also act as part of the RNA
      transcription apparatus, as well as nucleotide excision repair in plant cells.

PMID- 9524268
TI  - Implications of a common polymorphism in intron 12 of the dystrophin gene for
      deletion detection by multiplex PCR.
AB  - The multiplex polymerase chain reaction (PCR) is a reliable and efficient method
      for detecting dystrophin gene deletions in about 65% of patients with Duchenne or
      Becker muscular dystrophy (DMD or BMD). The 9-plex PCR assay, which
      simultaneously amplifies the muscle-specific promoter and exons 3, 6, 13, 43, 47,
      50, 52 and 60, is one of the multiplex PCR assays used routinely to test for DMD
      and BMD deletions. In this study, we describe a previously unrecognized A to G
      base variation in intron 12 (nt -110 from exon 13) of the dystrophin gene. This
      variant, located within the annealing site of the exon 13 forward primer,
      prevented amplification of exon 13 in the 9-plex PCR assay. Present in 56% (25 of
      45) of normal Caucasian alleles and 23% (3 of 13) of normal black American
      alleles, it is likely encountered frequently during dystrophin deletion analysis
      by multiplex PCR, and may complicate test result interpretation. Therefore, we
      suggest two modifications for the multiplex PCR detection of dystrophin gene
      deletion.

PMID- 9524269
TI  - Rhizobium etli cycHJKL gene locus involved in c-type cytochrome biogenesis:
      sequence analysis and characterization of two cycH mutants.
AB  - The cycHJKL gene locus was cloned from Rhizobium etli by the rescue of a Tn5mob
      insertion of a mutant (IFC01) which was affected in the production of c-type
      cytochromes. The cycH, cycJ, cycK and cycL genes are proposed to code for
      different subunits of a haem lyase complex involved in the attachment of haem to
      cytochrome c apoproteins. CycH of 365 aa shared 27, 36, 47 and 63% identity with
      CycH from Paracoccus denitrificans, Bradyrhizobium japonicum, R. meliloti, and R.
      leguminosarum, respectively. CycJ of 153 aa shared 52, 71, and 85% identity to
      the cycJ gene product of B. japonicum, R. meliloti, R. leguminosarum,
      respectively. CycK of 666 aa shared 62, 73, and 90% homology with CycK from B.
      japonicum, R. meliloti, and R. leguminosarum, respectively, while CycL of 151 aa
      shared 57, 67 and 86% homology with CycL from the abovementioned species. The
      Tn5mob insertion present in the IFC01 strain was located in the cycH gene. This
      strain was able to infect bean plants, but unable to fix nitrogen during
      symbiosis. A previously described R. etli cytochrome c-deficient MuD1lac-induced
      mutant (CFN4202) that induced empty nodules on Phaseolus vulgaris, also have
      lesions in cycH. Complementation analysis suggested that the MuD1lac insertion of
      the CFN4202 strain was polar on expression of genes downstream of cycH in
      contrast with the Tn5mob insertion present in IFC01, which showed no polarity on
      cycJKL. Our data suggest that CycH may not be essential for the infection
      process, but is necessary for nitrogen fixation.

PMID- 9524270
TI  - Cloning and heterologous expression of Entamoeba histolytica adenylate kinase and
      uridylate/cytidylate kinase.
AB  - We have isolated two cDNA clones encoding Entamoeba histolytica nucleotide
      kinases, EhAK and EhUK, expressed them in E. coli and performed functional
      studies of the recombinant enzymes. Nucleotide sequence analysis showed that EhAK
      and EhUK genes exhibited the features characteristic of E. histolytica genes,
      such as transcripts with relatively short 5' and 3' untranslated flanking regions
      containing the conserved E. histolytica transcription promoter elements located
      5' to the initiation codon and a polyadenylation signal in the 3' UTR, a
      distinctive codon usage bias for A or T in the third position and an AT bias
      greater than 75% in the flanking regions of the transcripts. At the protein
      level, both enzymes belong to the short variant nucleoside monophosphate (NMP)
      kinases, which lack a 29amino acid LID region present in the long variant
      isoenzymes. EhAK was 30-38% identical to the members of the adenylate kinase (AK)
      family while EhUK was more similar (48-49% identity) to UMP/CMP kinases. Both
      enzymes used ATP as preferred phosphate-group donor but each one exhibited strict
      specificity for the acceptor NMP, EhAK for AMP and EhUK for the pyrimidine
      nucleoside monophosphates UMP and CMP. Biochemical characterization of the
      enzymes and phylogenetic reconstruction showed that EhUK is an authentic and well
      conserved member of the UMP/CMP kinase group while EhAK is the most divergent
      member known of the AK1 isoenzymes.

PMID- 9524271
TI  - Structure and expression of the human Na,K-ATPase beta 2-subunit gene.
AB  - We cloned and characterized the human Na,K-ATPase beta 2-subunit gene. The gene
      encompasses over 8 kb at chromosome 17 in the human genome and is composed of
      seven exons. Primer extension analysis identified a major transcription
      initiation site 529 bases upstream of the translation start site. The 5'-flanking
      region of the gene harbors a potential TATA sequence, located 94 bases upstream
      of the transcription initiation site and a number of potential promoter and
      regulatory elements, among them a Sp1 site, at position -120. A functional Sp1
      site has also been found in the rat Na,K-ATPase beta 2-subunit gene (Kawakami,
      K., Watanabe, Y., Araki, M., Nagano, K., 1993). Sp1 binds to the adhesion
      molecule on glia regulatory element that functions as a positive transcription
      regulatory element in astrocytes. (J. Neurosci. Res. 35, 138-146). Putative
      AATAAA and TG sequences were found at positions 7018 and 7068, respectively.
      These signals delimit the origin of the the poly(A) tail and mark the end of the
      sequence that completes the 3'-UT downstream sequence of the human cDNA. An Alu
      repetitive sequence is located between positions 5961 and 6274. The gene is
      expressed as a single mRNA species, of 3.36 kb, which is present in cerebrum,
      cerebellum, kidney and heart, being more abundant in neural tissues. Structural
      analyses of this and other of the P-type ATPase beta subunit genes reveal that
      they evolved from a common ancestor.

PMID- 9524272
TI  - Characterization of rat 17 beta-hydroxysteroid dehydrogenase type 1 gene and mRNA
      transcripts.
AB  - In the present study, the gene encoding rat 17 beta-hydroxysteroid dehydrogenase
      type 1 (rHSD17B1 gene) was cloned and characterized. Like the analogous human
      gene (hHSD17B1), rHSD17B1 contains six exons and five introns spanning
      approximately 2.2 kb. The identity between the exons and introns of the two genes
      ranges from 58% to 82% and 42% to 57%, respectively. In contrast to hHSD17B1,
      rHSD17B1 is not duplicated. The cap site for rHSD17B1 was localized to position 
      41 upstream of the ATG translation initiation codon. Sequence comparison of the
      first 200 bp upstream of the cap site showed 72% identity between the human and
      rat HSD17B1 genes, including a conserved GC-rich area. Further upstream, no
      significant identity between the two genes was observed and several, cis-acting
      elements known to modulate the expression of hHSD17B1 are not conserved in the
      rat gene. Rat HSD17B1 unlike hHSD17B1 with two cap sites, possesses two
      polyadenylation signals, thus resulting in two mRNAs.

PMID- 9524273
TI  - Characterization of the murine gene of gC1qBP, a novel cell protein that binds
      the globular heads of C1q, vitronectin, high molecular weight kininogen and
      factor XII.
AB  - gC1qBP is a novel cell protein which was found to interact with the globular
      heads of C1q, high mol. wt kininogen, factor XII and the heparin-binding,
      multimeric form of vitronectin. The protein sequence shows no homology to any
      protein family. This paper describes the genomic organization of mouse gC1qBP and
      the characterization of its 5' flanking region. The mouse gene consists of six
      exons separated by five introns, and its total length is approximately 6kb. Exon
      1 encodes the putative signal peptide, a long stretch of 70 amino acid residues,
      and the first four amino acid residues found in the mature gC1qBP. Exons 2-5
      encode four very hydrophilic domains, whereas exon 6 encodes a neutral domain.
      The amino acid sequence responsible for binding to the heparin-binding,
      multimeric form of vitronectin is located in exon 2. A 1kb DNA fragment upstream
      of the first initiation codon was sequenced, which contained four potential TATA
      boxes, seven CAAT boxes, six SP1 sites and various putative transcription factor
      binding elements, indicating that the promoter region is in close proximity to
      the first exon. The mouseC1qbp gene was mapped to chromosome 11, closely linked
      to D11Mit4 using genomic DNAs from a (C57BL/6J x Mus spretus)F1 x Mus spretus
      backcross.

PMID- 9524274
TI  - An enhancer region within the copia untranslated leader contains binding sites
      for Drosophila regulatory proteins.
AB  - The untranslated leader region (ULR) of the Drosophila LTR retrotransposon copia
      is known to be critical to the element's expression in a variety of species. Two
      copia ULR size variants are prevalent in natural populations. The more
      transcriptionally active full length variants contain within their ULRs two
      tandemly repeated copies of a 28-bp region of dyad symmetry with a sequence
      similarity to the core sequence of the SV40 enhancer. The region of dyad symmetry
      contains two inverted repeats of a 8-bp motif (TTGTGAAA) that occurs at three
      additional locations within the ULR. The less active ULR gap variants differ from
      full length variants in that they contain only one copy of the 28-bp sequence. We
      show that the full length copia ULR in either orientation but not the gap ULR can
      significantly enhance expression of a minimal hsp 70 promoter. We demonstrate by
      EMSA that the full length ULR, the gap ULR and the 28-bp sequence are each
      capable of binding the Drosophila CCAAT/enhancer binding protein (DmC/EBP) and
      another previously uncharacterized factor, copia binding factor-1 (CBF-1).
      Another Drosophila protein previously implicated in fat body specific expression
      of the alcohol dehydrogenase gene (Adh), the Box-B-binding factor-2 (BBF-2), is
      also shown to bind to the copia ULR.

PMID- 9524276
TI  - Characterisation of the urease gene cluster in Bordetella bronchiseptica.
AB  - Bordetella bronchiseptica is a common ureolytic mammalian respiratory pathogen.
      The urease operon of this organism is encoded within an 8.9 kb DNA fragment which
      contains the structural genes (ureA, ureB and ureC) and accessory genes (ureD and
      ureG) homologous to other urease genes. Uniquely, the ureE and ureF genes are
      fused to form a hybrid protein, UreEF, which may result in tighter coordination
      of the putative functions of the individual accessory genes, nickel donation to
      the urease active site, and prevention of nickel incorporation until correct
      formation of the active site, respectively. The operon contains an additional
      open reading frame, UreJ, found only also in the Alcaligenes eutrophus urease
      operon. UreJ is also 37% homologous with HupE from Rhizobium leguminosarum bv.
      viciae, and may potentially be involved in nickel transport. A transcriptional
      activator, designated Bordetella bronchiseptica urease regulator (BbuR), is
      located directly upstream and in the opposite orientation to the urease operon.
      BbuR shares homology with members of the LysR regulatory protein family. LysR
      proteins have been shown to regulate urease in Klebsiella aerogenes (NAC), and
      catalase in Escherichia coli (OxyR), which offers the intracellular bacterium
      protection from phagolysosome damage. A putative BbuR binding site (5'-ATA-N9-TAT
      3'), identical to the NAC-binding consensus sequence, was found 27 bp upstream of
      the urease promoter in B. bronchiseptica. We hypothesise that BbuR controls
      urease expression which is involved in protection of intracellular B.
      bronchiseptica from phagolysosomal damage. Comparison of the urease promoter
      regions of B. bronchiseptica, Bordetella parapertussis ATCC15311 and the urease
      negative strain B. pertussis Tohama I revealed no differences in the ureD open
      reading frame between each species. A cluster of mutations in both B. pertussis
      and B. parapertussis was found upstream of the urease promoter, in a region
      proximal to the putative bbuR promoter. The inability of B. pertussis to produce
      urease may therefore reflect mutations in regulatory elements, and not mutations
      in the urease locus itself.

PMID- 9524275
TI  - Cloning the chicken leptin gene.
AB  - Chicken is characterized by a relative insulin resistance and a physiological
      hyperglycemia (2g/L) and is also subjected to fattening. Fat deposits in chicken,
      as in mammals, are regulated by environmental and genetic factors. In mammals,
      leptin, an adipose cell-specific secreted protein has been characterized that is
      encoded by ob gene. Leptin regulates satiety through hypothalamic specific
      receptors, energy balance, energy efficiency and contributes to adaptation to
      starvation. The leptin gene has been characterized in various mammalian species,
      and the cloning and sequencing of the chicken leptin gene (ob gene) are reported.
      Using RT-PCR and primers flanking the coding region of the leptin gene selected
      from known mammalian sequences, we have successfully amplified a 600-bp fragment
      from chicken liver and adipose tissue total ARNs. The amplified fragment exhibits
      a similar size to that of the coding region of the mammalian leptin gene. The
      sequences of the coding region of chicken liver and adipose tissue are identical
      and presented 97%, 96% and 83% similarity to the mouse, rat and human sequences,
      respectively. Finally, this is the first report showing that leptin gene
      expression in chicken is not exclusively localized in adipose tissue but is also
      expressed in liver. The expression of leptin in liver may be associated with a
      key role of this organ in avian species in controlling lipogenesis.

PMID- 9524277
TI  - Activation of rat androgen receptor by androgenic ligands is unaffected by
      antiandrogens in Saccharomyces cerevisiae.
AB  - The E. coli lacZ has been utilized as a reporter to evaluate ligand-mediated
      activation of the rat androgen receptor (AR) in Saccharomyces cerevisiae strain
      YCR1. beta-galactosidase activity was androgen-specific and was found to be
      inducible approximately 260-fold by dihydrotestosterone (DHT), testosterone and
      R1881. None of the antiandrogens tested was able to antagonize the DHT-dependent
      induction of beta-galactosidase activity. In the gel retardation assay, exposure
      of the receptor to DHT in vitro led to the formation of a protein-DNA complex
      that was not detected in yeast extracts unexposed to hormone. However, activation
      of AR by a steroidal (cyproterone acetate) and a non-steroidal antiandrogen
      (flutamide) either alone or in combination with DHT also results in a similar
      migration pattern. Additionally, LEM1, the ABC transporter that selectively
      modulates the biological potency of steroids in yeast, although operative in
      YCR1, was not responsible for antiandrogen resistance. These results thus
      indicate the involvement of other non-receptor factor(s) in mediating the effect
      of antiandrogens in yeast.

PMID- 9524278
TI  - The number of kringle IV repeats 3-10 is invariable in the human apo(a) gene.
AB  - The human apolipoprotein(a) (apo(a)) gene is a member of a family of related
      genes including plasminogen, apo(a)rg-B and apo(a)rg-C, which are clustered on
      chromosome 6q 2,7. Apo(a) contains ten different types of plasminogen-like
      kringle IV repeats (K-IV 1-10) one of which (K-IV 2) varies in number resulting
      in a remarkable size polymorphism of the protein. Sequence analysis of human
      apo(a) alleles and indirect evidence have suggested that K-IV 1 and K-IV 3-10 are
      each present once in individual alleles and that the 3' apo(a) region
      encompassing kringles IV 3-10, kringle V and the protease domain is invariable.
      To directly test this, we have constructed a restriction map of the apo(a) gene
      region from genomic DNA and from a yeast artificial chromosome (YAC) (K-IV 13)
      which contains the entire apo(a) gene. The presence of a 63 kb ClaI fragment
      encompassing kringles IV 3-10, kringle V and the protease domain and a 46 kb SwaI
      fragment, spanning kringles IV 5-10, kringle V and the protease domain was
      demonstrated by PFGE/Southern blotting in 30 unrelated subjects, who represented
      a range of apo(a) size alleles containing from 11 to 49 kringles. Our analysis
      demonstrates that the number of kringles IV 3-10 is invariable in the human
      apo(a) gene, suggesting that the 3'domain of Apo(a) is functionally important.

PMID- 9524279
TI  - Cloning and characterization of promoter and 5'-UTR of the NMDA receptor subunit
      epsilon 2: evidence for alternative splicing of 5'-non-coding exon.
AB  - Using rapid amplification of cDNA ends (RACE), we have cloned the 5'-untranslated
      region (5'-UTR) of the N-methyl-D-aspartate receptor subunit epsilon 2 from
      murine forebrain-derived mRNA. We identified two distinct types of cDNA species
      differing in the presence or absence of one exon sequence. Sequencing of the 5'
      non-coding region of the epsilon 2 gene revealed that the epsilon 2 5'-UTR
      consists of three untranslated exons located at least 20 kb upstream of exon 4
      that contains the ATG codon for initiation of translation. This genomic
      organization shows a close similarity to the epsilon 3 gene. The transcriptional
      start site was determined by primer extension assays. Expression of the
      alternative exon sequence was shown by in situ hybridization in the murine brain.
      Basal transcriptional activity of the epsilon 2 promoter was detected in
      different neuronal and non-neuronal cell lines with transient reporter gene
      expression assays. Potential SP1 and CREB binding sites were found in the
      promoter region. Specific binding of these transcription factors was demonstrated
      in electrophoretic mobility shift assays.

PMID- 9524280
TI  - Alternative splicing and genomic organization of the L5-67 gene of Aplysia
      californica.
AB  - The L5-67 gene was first identified on the basis of its high expression level in
      the LUQ neurons, a group of four giant cells located in the left upper quadrant
      of the abdominal ganglion of Aplysia californica. Its mRNA and peptides were
      later shown to be present in these cells, as well as in about 100 other smaller
      neurons in the CNS. L5-67 propeptide and/or mature peptides are also present in
      peripheral organs, particularly in the kidney, which is the target of most LUQ
      processes. Using RT-PCR, we show the presence of an alternatively spliced L5-67
      transcript arising from the exclusion of the fourth exon from the mature mRNA.
      This alternative splicing event occurs specifically in the kidney, although we
      could not identify the cells in which it takes place. Translation of this
      transcript generates a 52 amino acid (aa) propeptide in which the first N
      terminal 45 aa are identical to the original L5-67 propeptide. The last seven C
      terminal aa are unrelated to the previously characterized L5-67 peptides due to a
      change in the open reading frame.

PMID- 9524281
TI  - Isolation and genomic characterization of the TUPLE1/HIRA gene of the pufferfish
      Fugu rubripes.
AB  - In an effort to obtain a small genomic construct for the generation of a HIRA
      transgenic mouse, we have isolated and sequenced the Fugu TUPLE1/HIRA gene. We
      have compared the gene organization and the proteins encoded in pufferfish and
      human and also searched for conserved DNA sequences that might be important in
      gene regulation. The pufferfish gene spans approx. 9 kb, which is approx. 11
      times smaller than the human gene, owing to the reduced size of the introns. Like
      its human counterpart, it is organized into 25 exons. The majority of the splice
      sites are in identical positions to those found in the human gene, however, for
      three internal exons the positions of the splice sites are not directly
      comparable. The coding regions are almost identical in size and show a high
      degree of similarity, especially at the amino and carboxy termini. Comparisons of
      5' and 3' sequences failed to detect similarities or sequences involved in
      regulation.

PMID- 9524282
TI  - Mouse lysosomal acid lipase: characterization of the gene and analysis of
      promoter activity.
AB  - Lysosomal acid lipase (LAL) is required for the hydrolysis of intracellular
      cholesteryl esters and triglycerides that are delivered to lysosomes by low
      density lipoprotein (LDL) receptor-mediated endocytosis. To understand that the
      expression of LAL mRNA and protein is tissue and cell specifically regulated in
      mice, genomic clones for the mouse lysosomal acid lipase (mLAL) gene were
      isolated and characterized. The 6.8 kb of the mLAL gene 5'-flanking region was
      sequenced. Comparisons of mouse and human LAL genes organization revealed
      identical intron/exon boundaries, except for intron 1 of the mouse gene, and
      identical exonic length of exons 3-9. The transcription start sites and exon 1 of
      mLAL were characterized by 5'-RACE-PCR and S1 nuclease mapping. Transfection of
      5' flanking deletions of mLAL luciferase reporter gene construct identified
      positive and negative regulatory elements that varied with cell type.
      Transfection of three progressively smaller pieces of intron 1 inserted into an
      SV40 promoter and luciferase reporter gene revealed an enhancer-like activity in
      intron 1 that is also cell type specific. These studies provide insight into the
      basis for regulation of this critical enzyme in lipid metabolism.

PMID- 9524283
TI  - Genomic organization of the flt-1 gene encoding for vascular endothelial growth
      factor (VEGF) receptor-1 suggests an intimate evolutionary relationship between
      the 7-Ig and the 5-Ig tyrosine kinase receptors.
AB  - The flt-1 tyrosine kinase gene encodes a high affinity receptor for Vascular
      Endothelial Growth Factor, and belongs to the so-called '7-Ig' or flt gene family
      which has characteristics of 7-Immunoglobulin (Ig)-like domains in the
      extracellular region. This is structurally distantly related to 5-Ig domain
      containing receptors such as Fms/Kit/PDGF-R. However, the whole genomic
      organization for any 7-Ig receptor gene has not been determined yet. To examine
      the genomic structure of flt-1 and the evolutionary relationship between genes of
      the 7-Ig and 5-Ig receptor families, we isolated the mouse genomic DNAs carrying
      all exons of the flt-1 gene. The mouse flt-1 gene consisted of 30 exons, whose
      exon-intron boundaries were highly related to those in the 5-Ig receptor genes,
      except for the amino terminal region. The sequences corresponding to the first
      and second Ig-domains in the flt-1 gene were encoded by four exons, whereas this
      region was encoded by only two exons in the 5-Ig receptor genes. These results
      raise the interesting possibility that deletion or insertion mutations of introns
      in one of these receptor genes took place in the evolutionary generation of the
      other receptor genes.

PMID- 9524284
TI  - Identification of N-terminal minimal transactivation domain of CBP, p300 and
      caenorhabditis elegans homologues.
AB  - CBP/p300 is a multidomain transcriptional cofactor that acts in junction with
      other factors to regulate transcription. To elucidate the domain function of CBP,
      we fused its dissected fragments to Ga14 DNA-binding domain and transfected the
      deletion mutants into several cell lines. First, we found that the minimal
      transactivation domain (MTD) at the N-terminal portion maps to between 344 and
      451 aa, and shows activity in a cell-type dependent manner. Second, we cloned C.
      elegans homologues corresponding to the MTD by RT-PCR and identified the three
      related products, two of which exhibited weak transcriptional activity. Finally,
      by means of the yeast two hybrid screening using MTD as a bait, we cloned hypoxia
      inducible factor (HIF) 1 alpha and Stat2 cDNAs. These results suggested a
      functional role of MTD located at the N-terminal region of CBP/p300 in connecting
      to transcriptional factors.

PMID- 9524285
TI  - The Ld Cht1 gene encodes the secretory chitinase of the human pathogen Leishmania
      donovani.
AB  - Leishmania donovani promastigotes were shown to release chitinase activity during
      their growth in vitro. A PCR-based strategy identified a single copy ORF capable
      of encoding the L. donovani chitinase (Ld Cht1, 1374 bp). Ld Cht1 was shown to be
      actively transcribed by L. donovani promastigotes using reverse transcription and
      PCR amplification. The deduced aa sequence of Ld Cht1 showed high conservation to
      known chitinases including the putative active and two substrate binding sites.
      Antiserum generated against four peptides derived from its deduced aa sequence
      immunoprecipitated an approx. 50-kDa in vitro transcription/translation product
      of Ld Cht1. Further, this antiserum also immunoprecipitated both the native L.
      donovani 50-kDa Cht1 protein and the native chitinase activity synthesized and
      released by these parasites. Cumulatively, these data demonstrated that Ld Cht1
      encoded the chitinase of this important human pathogen.

PMID- 9524286
TI  - Characterization of the 5' flanking region of the Xenopus laevis transforming
      growth factor-beta 5 (TGF-beta 5) gene.
AB  - Transforming growth factors-beta are potent regulators of cellular proliferation,
      differentiation and morphogenesis. 2.41 kb of the 5' flanking region of the
      transforming growth factor-beta 5 (TGF-beta 5) gene has been isolated from a
      Xenopus laevis genomic library and sequenced. The transcription start site of
      this gene was determined by 5' RACE method. Promoter activity was demonstrated by
      transient transfection experiments using luciferase reporter gene constructs in
      XTC cells. A number of putative recognition sites for transcription factors were
      found in the 5' flanking region of the TGF-beta 5 gene.

PMID- 9524290
TI  - Analysis of serum cytokine levels in primary biliary cirrhosis patients and
      healthy adults.
AB  - By using commercially available ELISA kits, serum IL-6 and TNF-alpha levels in
      healthy adults, and the levels of various cytokines in patients with primary
      biliary cirrhosis or chronic viral liver diseases, were investigated. IL-6 levels
      of healthy subjects were distributed in a wide range, and the distribution
      pattern was similar to those of the patients. TNF-alpha levels tended to be low
      in females in their 30s, but there were no abnormalities in the patients.
      Characteristic findings, in the primary biliary cirrhosis patients, were an
      increase of IFN-gamma and IL-2 levels, and a decrease of GM-CSF levels (P <
      0.05). IL-8 levels were higher in the patients than in the healthy subjects (P <
      0.05), and the increase was remarkable in chronic viral liver disease patients.
      We believe that measurement of serum cytokine levels as a clinical immunological
      test is highly useful. Further development of simpler, more rapid, and more
      sensitive analysis methods is desired.

PMID- 9524287
TI  - Hepatitis C virus core protein represses p21WAF1/Cip1/Sid1 promoter activity.
AB  - Hepatitis C virus (HCV) often causes a prolonged and persistent infection, and an
      association between hepatocellular carcinoma (HCC) and HCV infection has been
      noted. Recent experimental evidence using a cloned genomic region suggests that
      the putative core protein of HCV has numerous biological properties and is
      implicated as a viral factor for HCV mediated pathogenesis. WAF1/Cip1/Sid1 (p21)
      is the prototype of a family of proteins that inhibit cyclin-dependent kinases
      (CDK) and regulate cell cycle progression in eukaryotic cells. In this study, we
      have observed that the HCV core protein represses the transcriptional activity of
      the p21 promoter when tested separately by an in-vitro transient expression assay
      using murine fibroblasts (NIH3T3), human hepatocellular carcinoma (HepG2), and
      human cervical carcinoma (HeLa) cells. A deletion analysis of the p21 promoter
      suggested that the HCV core responsive region is located downstream of the p53
      binding site. A gel mobility shift analysis showed that the HCV core protein does
      not bind directly to p21 regulatory sequences. Thus, the HCV core protein appears
      to act as an effector in the promotion of cell growth by repressing p21
      transcription through unknown cellular factor(s).

PMID- 9524291
TI  - Flow cytometric analysis of IL-6 receptors on peripheral lymphocytes in patients
      with primary biliary cirrhosis.
AB  - Interleukin-6 receptors (IL-6R) and interleukin-1 receptors (IL-1R) on lymphocyte
      surfaces were analyzed, using flow cytometry and dye-labeled IL-6 and IL-1 beta,
      to examine the clinical and immunological significance of these receptors.
      Incubation of peripheral blood mononuclear cells in the presence of mitogen
      resulted in a remarkable increase of lymphocytes expressing the IL-6 and IL-1
      beta receptors on the cell surface. The increase in lymphocytes bearing these
      cytokine receptors may reflect an increase in stimulated lymphocytes. When
      peripheral blood from patients with primary biliary cirrhosis (PBC) was examined
      for these receptors, the percentage of IL-6R positive cells was significantly
      higher in the patients than in healthy controls (P < 0.01). The increase in IL-6R
      positive cells was only significant for the T lymphocyte fraction (P < 0.01). No
      significant change in IL-1R was observed. There was a significant positive
      correlation between the percentage of IL-6R positive T lymphocytes and the titer
      of antimitochondrial antibody in patients with PBC. These findings concerning IL
      6R may be noteworthy elucidating autoimmune etiological features of PBC.

PMID- 9524293
TI  - Changes in serum carbohydrate-deficient transferrin and gammaglutamyl transferase
      after moderate wine consumption in healthy males.
AB  - Serum carbohydrate-deficient transferrin (CDT) concentrations and gammaglutamyl
      transferase (GGT) activities were measured in the fasting serum of healthy male
      subjects before and after 4 weeks consumption each day of 375 ml wine or 500 ml
      grape juice. After wine consumption, serum CDT concentrations rose in 38 of 48
      individual test procedures, and the mean +/- SEM increased from 17.8 +/- 0.86 u/l
      to 20.9 +/- 1.14 u/l (t0 = 4.66; P < 0.001). Serum GGT activity rose in 35 of
      these test procedures, and the mean +/- SEM increased from 19.6 +/- 1.40 u/l to
      22.3 +/- 1.79 u/l (t0 = 3.58; P < 0.001). When wine consumption was followed by 2
      weeks of abstinence from alcohol, significant reductions in both CDT and GGT were
      noted, virtually reaching baseline levels. No significant change in either index
      occurred after 4 weeks of consuming grape juice. The correlation between CDT and
      GGT was rather low, suggesting that their responses to alcohol occur by different
      mechanisms. The results indicate that the response of CDT to alcohol dose is
      continuous, and that even moderate consumption can cause significant elevations
      in a healthy population.

PMID- 9524292
TI  - DNA extraction from human urinary sediment.
AB  - DNA was extracted from urinary sediments and was sufficient for polymerase chain
      reaction (PCR) and enzymatic analysis, even if DNA from microorganisms coexisted.
      From urine samples, the yield of DNA ranged from trace levels to 20 micrograms
      per 10 mL urine. When urinary sediment was stored in ethanol, DNA remained stable
      for 2 weeks or more. Individual identification and sex determination could easily
      be performed using either fresh or ethanol-fixed urine. In conclusion, urine can
      be used as a source for PCR-based investigations and genetic studies.

PMID- 9524294
TI  - Optimal conditions of immune complex transfer enzyme immunoassays for antibody
      IgGs to HIV-1 using recombinant p17, p24, and reverse transcriptase as antigens.
AB  - The immune complex transfer enzyme immunoassays for antibody IgGs to p17, p24,
      and reverse transcriptase (RT) of HIV-1 were tested under various conditions.
      Antibody IgGs to HIV-1 were reacted for up to 20 hr with 2,4-dinitrophenyl-bovine
      serum albumin-recombinant HIV-1 protein conjugates and recombinant HIV-1 protein
      beta-D-galactosidase conjugates, and the immune complexes formed, comprising the
      three components, were trapped onto polystyrene beads coated with (anti-2,4
      dinitrophenyl group) IgG by incubation at 4-30 degrees C for up to 2 hr with
      shaking and were transferred onto polystyrene beads coated with (antihuman IgG
      gamma-chain) IgG in the presence of excess of epsilon N-2,4-dinitrophenyl-L
      lysine by incubation at 4-30 degrees C for up to 2 hr with shaking. When serum
      randomly collected from an HIV-1 seropositive subject and serum included in an
      Western blot kit were tested, the formation of the immune complex was almost
      completed within 1 hr for antibody IgG to p17, within 1-2 hr for antibody IgG to
      p24 and within 4 hr for antibody IgG to RT. Even for antibody IgG to p17,
      however, the immune complex continued to be formed for at least 2 hr, when serum
      samples at early stages of HIV-1 infection were tested. Trapping and transferring
      of the immune complexes were faster at higher temperatures and were almost
      completed within 0.5-1.5 hr, although the amount of the immune complexes trapped
      and transferred at 25 and/or 30 degrees C increased for 0.5-1 hr, but
      subsequently tended to decline. When the formation, trapping, and transferring of
      the immune complexes were performed for 0.5, 1, and 1 hr, respectively, with
      shaking followed by 1 hr assay of bound beta-D-galactosidase activity, the
      sensitivities for antibody IgGs to p17, p24, and RT using 10 microliters of serum
      samples were similar to or significantly higher than those of the corresponding
      previous immune complex transfer enzyme immunoassays using 10 microliters of
      serum samples, in which the formation, trapping, and transferring of the immune
      complexes were performed for 3, 16, and 3 hr, respectively, without shaking,
      followed by 2.5 hr assay of bound beta-D-galactosidase activity, and the
      sensitivities for antibody IgGs to p17, p24, and RT using 100 microliters of
      serum samples were 21-22-fold, 5.5-6.3-fold, and 5.3-6.0-fold, respectively,
      higher. When each period of time for the formation, trapping, and transferring of
      the immune complexes was prolonged to up to 4 hr, the sensitivities for antibody
      IgGs to p17, p24, and RT using 100 microliters of serum samples were improved 88
      93-fold, 15-17 fold and 20-24-fold, respectively, as compared with those of the
      previous ones.

PMID- 9524295
TI  - Reactivity of chagasic antigal antibodies with noninfected cells treated with
      Trypanosoma cruzi secreted/excreted antigens.
AB  - Here, we show that antigal antibodies from Chagas' disease patients react with
      noninfected host cells previously treated with antigens secreted by the
      trypomastigote forms of Trypanosoma cruzi. With the exception of human and Old
      World monkey cells, which are GAL-negative, cells of all mammals express the GAL
      epitope (Gal alpha (1-3)Gal beta (1-4)GlcNAc-R) on their surface. Thus only the
      former ones develop antigal antibodies. Antigal antibodies increase during
      infection with T. cruzi, which expresses GAL epitopes on the surface of the
      infective forms. Here, we show that incubation of noninfected, GAL-negative cells
      with antigens shed by T. cruzi renders these cells reactive to antigal antibodies
      purified from chagasic sera. Neither chagasic sera depleted of antigal antibodies
      nor antigal antibodies purified from normal sera display reactivity with treated
      cells. Cell reactivity of chagasic antigal was abolished in the presence of
      melibiose (Gal alpha (1-6)Glc) or gal-gal (methyl 3-O-alpha-D-galactopyranosyl
      alpha-D-galactopyranoside). Since shedding of T. cruzi antigens can occur in
      vivo, these antigens may induce reactivity of chagasic antigal with noninfected
      human cells. The reactivity of noninfected, GAL-negative cells observed only with
      chagasic antigal antibodies can amplify the range of reactivity of these
      antibodies and consequently adds to their importance in the pathogenesis of human
      Chagas' disease.

PMID- 9524296
TI  - Optimal conditions of immune complex transfer enzyme immunoassay for p24 antigen
      of HIV-1.
AB  - In the immune complex transfer enzyme immunoassay for HIV-1 p24 antigen,
      different preparations of anti-p24 Fab'-beta-D-galactosidase conjugate, various
      periods of time for immunoreactions involved, and shaking for incubations with
      polystyrene beads were tested. On the basis of the results of these experiments,
      p24 antigen was measured as follows. The antigen was reacted simultaneously with
      2,4-dinitrophenyl-biotinyl-bovine serum albumin-affinity-purified rabbit anti-p24
      Fab' conjugate and highly polymerized monoclonal mouse anti-p24 Fab'-beta-D
      galactosidase conjugate at 37 degrees C for 2 hr. The immune complex formed
      comprising the three components was trapped onto colored polystyrene beads coated
      with affinity-purified (anti-2,4-dinitrophenyl group) IgG for 1.5 hr and was
      transferred to white polystyrene beads coated with streptavidin in the presence
      of epsilon N-2,4-dinitrophenyl-L-lysine for 1.5 hr. The incubations with
      polystyrene beads were performed at room temperature with shaking. beta-D
      Galactosidase activity bound to the white polystyrene beads was assayed by
      fluorometry at 30 degrees C for 2 hr. The detection limit of p24 antigen (0.1
      amol/tube and 10 amol (0.24 pg)/ml of serum) was equal to that obtained when the
      formation, trapping, and transferring of the immune complex were performed for 4,
      16, and 3 hr, respectively, by incubation without shaking. Namely, the period of
      time required for the immune complex transfer enzyme immunoassay of p24 antigen
      was markedly shortened (25.5-7 hr) without loss of the sensitivity. By the
      improved immune complex transfer enzyme immunoassay, p24 antigen was detected 12
      20 days earlier than the detection of antibodies to HIV-1, i.e., seroconversion
      by the conventional ELISA.

PMID- 9524297
TI  - Quantitative measurement of serum HCV RNA in patients with chronic hepatitis C:
      comparison between Amplicor HCV monitor system and branched DNA signal
      amplification assay.
AB  - Quantitative measurement of serum hepatitis C virus (HCV) RNA is important in
      predicting and monitoring the therapeutic effects of interferon in treating
      patients with chronic hepatitis C. We compared two commercial available assays,
      Roche Amplicor HCV Monitor test kits and Chiron branched DNA signal amplification
      (bDNA) assay, in quantitative measurement of serum HCV RNA in 74 patients with
      chronic hepatitis C. The serum HCV RNA of each of these patients was
      qualitatively positive by conventional reverse transcription-nested polymerase
      chain reaction. Serum HCV RNA was detected positive by the Amplicor test kits in
      63 (85%) patients and by the bDNA assay in 58 (78%) patients (P > 0.05). The
      quantitative results of HCV RNA detected by both assays showed a good linear
      correlation (r = 0.56, P < 0.001). Amplicor test kits detected 5 patients with
      low viremia which were below the detection limit of the bDNA assay (2.0 x 10(5)
      genome equivalents/ml). However, the mean HCV RNA values detected by the Amplicor
      test kits was 1.26 log lower than that of the bDNA assay. The Amplicor test kits
      detected only 5 samples (8%) with a HCV RNA value greater than 5 x 10(6)
      copies/ml, while the bDNA assay detected 23 samples (40%) with a HCV RNA value
      greater than 5 x 10(6) genome equivalents/ml (P < 0.01). HCV genotype did not
      affect the positive rate of HCV RNA measurement detected by both assays. However,
      a significantly higher mean serum HCV RNA value was noted in HCV genotype 1b as
      compared with the other genotypes. We concluded that the Roche Amplicor HCV
      Monitor test kits and the Chiron branched DNA signal amplification assay are
      equally sensitive in the quantitative measurement of serum HCV RNA in patients
      with chronic hepatitis C and can be reliably used in measuring HCV viremia
      clinically.

PMID- 9524298
TI  - Rapid screening test for tuberculosis using a 38-kDa antigen from Mycobacterium
      tuberculosis.
AB  - A screening test for the diagnosis of tuberculosis by immunodot (IDt) is
      described, using an antigen of Mycobacterium tuberculosis, namely, a 38-kDa
      glycoprotein which has shown great specificity in previous serologic analyses.
      The test was used to examine 28 sera from patients with lung tuberculosis. Of
      these, 85% were positive by micro-ELISA and by the IDt test herein described.
      Control sera from healthy subjects (n = 20) gave negative results for ELISA and
      for IDt, which indicates that the screening test is highly specific. The test is
      easy to handle and requires no equipment and is therefore particularly useful for
      field studies.

PMID- 9524299
TI  - Preliminary development of the Children's Physical Self-Concept Scale.
AB  - The development of a healthy eating style and physical fitness regimen in
      adolescence or adulthood might be contingent on physical self-concept in
      childhood. Most available measures of physical self-concept are inappropriate for
      use with 1st and 2nd grade children, so the present study developed, piloted, and
      partially validated the 27-item Children's Physical Self-Concept Scale (CPSS),
      which assesses Global physical self-concept and subscales of Physical
      Performance, Physical Appearance, and Weight Control behaviors in children 6 to
      11 years of age. The test exhibits adequate test-retest reliability and internal
      consistency. A comparison of 316 normal and overweight children indicated that
      normal-weight children obtained higher Global physical self-concept scores and
      higher subscale scores. In addition, the CPSS distinguished test groups of
      diabetic, overweight, and normal-weight children in a contrasted-groups analysis.

PMID- 9524300
TI  - Visual acuity development and fatty acid composition of erythrocytes in full-term
      infants fed breast milk, commercial formula, or evaporated milk.

PMID- 9524301
TI  - A preliminary study of factors associated with psychological adjustment and
      disease course in school-age children infected with the human immunodeficiency
      virus.
AB  - This study consisted of a longitudinal examination (baseline and approximately 2
      yr follow-up) of factors associated with psychological adjustment in a sample of
      24 school-age children infected with the human immunodeficiency virus (HIV).
      Measures of depression, anxiety, and self-concept were administered to the
      children, and measures of behavioral problems, social functioning, and negative
      life events were administered to the parents. Generally, psychological adjustment
      seemed stable, though a decrease in positive social self-concept over time was
      observed. Negative life events were significantly associated with greater adverse
      psychological and behavioral outcomes at both baseline and follow-up. An
      additional component to the study investigated factors associated with survival.
      Examination of an additional five children who died within 12 months of baseline
      indicated that they experienced significantly more adverse life events, were less
      resilient, and had greater disease progression. The sample size was small and
      requires that these findings be considered as preliminary and suggestive rather
      than conclusive.

PMID- 9524302
TI  - Direct home observations of the prompting of physical activity in sedentary and
      active Mexican- and Anglo-American children.
AB  - Social interactions are important correlates of physical activity in children.
      Previous studies used global measures; the present study examined the influence
      of specific social interactions on immediate physical activity in children with
      data obtained from the Behaviors of Eating and Activity for Child Health:
      Evaluation System (BEACHES). The study examined parental and peer prompting of
      physical activity at home among 178 Mexican-American and 113 Anglo-American
      children at age 4 years and again at age 6.5 years. Most activity prompts came
      from adults interacting with children when they were sedentary. A reduction in
      the frequency of prompts from baseline to follow-up occurred in the prompter
      group (adult or child peer), gender, ethnicity, and preprompted activity level
      categories. Children's responses to these prompts showed that as they aged, they
      seemed to rely less on the interpersonal (especially adult) aspects of their
      environment for cues to be more active.

PMID- 9524303
TI  - Adolescents' health attitudes and adherence to treatment for insulin-dependent
      diabetes mellitus.
AB  - Adolescents' health attitudes and adherence to treatment for insulin-dependent
      diabetes mellitus (IDDM) were evaluated using the protection motivation theory
      (PMT). We expected cognitive appraisals of adherence (self-efficacy for treatment
      management, response efficacy of treatment, response costs of adherence) to be
      more influential for adherence than appraisals of nonadherence (rewards of
      nonadherence, perceptions of the risks of nonadherence, perceived severity of the
      risks). Adolescents (N = 101) with IDDM completed self-report measures of
      treatment adherence and of the PMT variables. Hierarchical regression analyses
      revealed that cognitions concerning adherence explained a statistically
      significant proportion of the variance in treatment adherence (sr2 = .17).
      Response costs of adherence produced the strongest correlations with overall
      adherence and with three of the four individual components of IDDM treatment
      (insulin injections, blood glucose monitoring, diet). The findings suggest that
      persuasive health communications might focus on appraisals of adherence rather
      than on risks of nonadherence.

PMID- 9524304
TI  - School should begin at age 3 years for American children.

PMID- 9524305
TI  - Recurrent episodes of asthma in a 10 year old.

PMID- 9524306
TI  - Clinical assessment and management of chronic pain and pain-associated disability
      syndrome.

PMID- 9524307
TI  - Drug targeting: where are we now and where are we going?

PMID- 9524308
TI  - Targeting technologies--the expanding patent literature.
AB  - Progress in the development of drug targeting technologies is advancing at an
      ever-increasing rate as we hurtle toward the new millennium. Examination of just
      the past three years of the drug delivery technology patient literature suggests
      that what was previously thought impossible may now be a reality. As one goes
      through this literature, the breadth and ingenuity of many of these approaches
      are obvious. As in the inaugural article, I have grouped information gathered
      from this search into areas of mucosal targeting, organ and/or tissue targeting,
      tumor targeting and focal delivery. The patent applications described in this
      article represent a sampling of the work in these areas, with particular
      attention being paid to a few of the more novel or intriguing claims.

PMID- 9524309
TI  - Nuclear import of DNA--the ultimate targeting in gene therapy.

PMID- 9524311
TI  - The interaction of phospholipid liposomes with bacteria and their use in the
      delivery of bactericides.
AB  - Liposomes have been prepared from dipalmitoylphosphatidylcholine (DPPC)
      incorporating the cationic lipids stearylamine (SA), dimethyldioctadecylammonium
      bromide (DDAB) and dimethylaminoethane carbamoyl cholesterol (DCchol) and the
      anionic lipids dipalmitoylphosphatidylglycerol (DPPG) and phosphatidylinositol
      (PI). Their adsorption to biofilms of skin-associated bacteria (Staphylococcus
      epidermidis and Proteus vulgaris) and oral bacteria (Streptococcus mutans and
      sanguis) has been investigated as a function of mole % cationic and anionic
      lipid. Targeting (adsorption) was most effective for the systems DPPC-chol-SA,
      DPPC-DPPG and DPPC-PI liposomes to S. epidermidis. The effect of extracellular
      mucopolysaccharide on targeting was investigated for S. epidermidis biofilms. It
      was found that targeting increased with the level of extracellular
      mucopolysaccharide for all liposome compositions studied. The delivery of the oil
      soluble bactericide Triclosan and the water soluble bactericide chlorhexidine was
      studied for a number of liposomal compositions. Superior delivery of both
      bactericides relative to the free bactericide occurred for DPPC-chol-SA liposomes
      and for Triclosan delivery by DPPC-DPPG and DPPC-PI liposomes targeted to S.
      epidermidis at low bactericide concentrations. DPPC-chol-SA liposomes were also
      effective for delivery of Triclosan to S. sanguis biofilms. Double labelling
      experiments using [14C]-chlorhexidine and [3H]-DPPC suggested that there was
      exchange between adsorbed liposomes which had delivered bactericide to the
      biofilm and those in the bulk solution implying a diffusion mechanism for
      bactericide delivery.

PMID- 9524310
TI  - Sensitized liposomes as an antigen delivery system for the stimulation of mucosal
      immunity.
AB  - This study was designed to exploit the ability of Peyer's patch M cells to
      recognize antigen-antibody complexes in the targeted delivery of a model antigen
      for the induction of mucosal immunity. Sensitized liposomes consisted of an
      entrapped model antigen, ovalbumin (OVA), and coated with unrelated antigen
      antibody complexes. Sensitized liposomes were administered intrajejunally to mice
      either with or without monophosphoryl lipid A (MLA). Humoral immune responses
      were monitored in saliva, feces, serum, and bile. Mice which received sensitized
      liposomes showed up to 4-fold amounts of specific IgA in saliva, feces, and bile
      compared to controls. Transient increases in anti-OVA IgA and IgG were observed
      in serum. Formulations including MLA generated positive anti-OVA IgG responses in
      both serum and bile. In separate experiments, cell proliferation studies were
      performed with Peyer's patch lymphocytes harvested from mice immunized with OVA
      in either standard or sensitized liposomes. Lymphocytes from test mice receiving
      only sensitized liposomes proliferated in the presence of OVA, but not an
      unrelated antigen. Taken together, these results support the potential
      application of antigen-antibody complexes in the stimulation of mucosal immune
      responses and that MLA may play an important role in overcoming OVA
      tolerogenicity.

PMID- 9524312
TI  - The influence of the sample preparation on plasma protein adsorption patterns on
      polysaccharide-stabilized iron oxide particles and N-terminal microsequencing of
      unknown proteins.
AB  - The in vivo organ distribution of i.v. injected drug carriers is strongly
      influenced by the adsorption of plasma proteins after i.v. injection, e.g. uptake
      by the mononuclear phagocytic system (MPS). 2-D PAGE could be established to
      analyze plasma protein adsorption patterns on polysaccharide-stabilized aqueous
      iron oxide dispersions used as contrast agents in Magnetic Resonance Imaging
      (MRI). After incubation in human plasma, centrifugation, a washing procedure and
      a solubilization step were carried out to obtain the proteins adsorbed onto these
      ultrasmall particles (65 nm in diameter). Patterns of adsorbed proteins were
      analyzed in dependence on the washing medium used, i.e. highly purified water,
      phosphate buffered saline and Krebs buffer pH 7.4. Conductivity and composition
      of the washing medium influenced the adsorption of IgG onto the particles, but
      had little effect on the other proteins present. IgG was strongly reduced when
      using the relatively high conductive buffers. The more stabilizing polysaccharide
      was desorbed the larger was the total amount of adsorbed proteins. Appearance of
      two unknown chains of spots in the range of appr. 92 kDa, accounting for appr.
      10% and 2% of the overall detected protein amount, was observed only when using
      Krebs buffer during the washing process. Performing N-terminal microsequencing
      one unknown chain of spots could be identified as a dimer of fibrinogen gamma
      chains.

PMID- 9524313
TI  - Lectins for drug delivery within the oral cavity--investigation of lectin binding
      to oral mucosa.
AB  - The aim of this study was to identify receptors present on the buccal mucosa in
      order to select appropriate lectins that will allow the retention of a dosage
      form within the oral cavity. Studies using human buccal cells, the avidin-biotin
      complex/diaminobenzidine method for identifying lectin binding and a
      microdensitometer to allow a semi-quantitative analysis of stain intensity,
      showed a wide diversity of lectin receptors. Kinetic studies of lectin binding to
      buccal cells revealed significant binding after 20 s, particularly for lectins
      from Pisum sativum and Arachis hypogaea. A significant reduction in lectin
      binding was observed after exposing buccal cells to a series of lectin solutions
      pre-treated with a large excess of secretor or non-secretor saliva. However when
      bound to the buccal cells, there was little displacement of lectins on exposure
      to either saliva types. Further studies on rat oral tissue suggested that the
      lectins appeared to bind to varying degrees on whole oral epithelial surfaces
      although differences in binding between this and the human buccal cell model were
      evident. It was concluded that a wide range of possible target receptors for
      lectins are present on rat oral epithelium and human buccal cells. Lectin binding
      to these receptors can be affected by the exposure time and the presence of
      saliva.

PMID- 9524314
TI  - Pharmacokinetic examination of p-aminobenzoic acid passage through the placenta
      and the small intestine in rats.
AB  - In the present study the permeability of the rat small intestine and the placenta
      to p-aminobenzoic acid (PABA) and antipyrine (AP) was investigated. Perfusion of
      the rat term placenta was used to determine the materno-fetal transfer of both
      compounds. PABA appeared in the fetal compartment faster than AP (ktransfer =
      0.064 and 0.046 min-1, respectively). The rate of equilibration between the
      maternal and fetal compartments and placental clearance were lower for PABA than
      for AP (kequilibration = 0.011 and 0.020 min-1; Clp = 0.22 and 0.33 ml/min,
      respectively); the feto-maternal concentration ratios at equilibrium (FMCReq)
      were, however, mutually comparable. Similarly, PABA proved to be absorbed from
      the small intestine significantly faster than AP (ka = 0.824 min-1 and 0.479 min
      1; tmax = 3.1 min and 8.9 min, respectively). The apparent volume of distribution
      (Vd) of AP in non-pregnant animals showed that the drug is distributed into the
      whole body water as expected (Vd = 0.66 l/kg); however, Vd of AP in pregnant
      animals was estimated to be 1.81 l/kg. Vd of PABA in non-pregnant animals showed
      its partially limited distribution, which was only slightly increased in the
      pregnant animals. Our results confirmed a faster penetration of hydrophilic PABA
      across the placenta and the small intestine than that of lipophilic AP. The
      mechanism of transplacental passage of PABA, however, remains to be determined.

PMID- 9524315
TI  - Characterization of fibromodulin isolated from bovine periodontal ligament.
AB  - Although several proteoglycans (PGs) have been reported in bovine periodontal
      ligament (PDL), the composition of PGs in PDL has been poorly characterized. In
      the present study, we isolated and characterized keratan sulfate-substituted PG
      (fibromodulin) in bovine PDL. Fibromodulin was purified from 4 M guanidine
      hydrochloride (GdmCl) extracts of bovine PDL tissues using DEAE Sephacel ion
      exchange chromatography and preparative electrophoresis. Fibromodulin appeared as
      a single polydisperse band with an apparent molecular weight (MW) of 80,000 (80
      kDa) on SDS-PAGE. Digestion of fibromodulin with keratanase or neuraminidase
      reduced the apparent molecular size, and N-glycanase treatment produced core
      protein bands of around 40 kDa. Fibromodulin reacted with keratan sulfate
      monoclonal antibody (5D4) and fibromodulin polyclonal antibodies (alpha-FM). The
      keratanase-digested fibromodulin reacted with alpha-FM, but not with 5D4. These
      data suggest that fibromodulin is one of the small PGs in the PDL-matrix and may
      fulfill construction and maintenance functions in this tissue.

PMID- 9524316
TI  - Lactoferrin impedes epithelial cell adhesion in vitro.
AB  - In the process of host defence against microbial challenge, neutrophils release
      granule contents with the potential side effect of damaging structural tissues.
      In the junctional epithelium such damage may contribute to the degeneration and
      renewal of the epithelial cells attached directly to the tooth (DAT cells), and
      subsequently to periodontal pocket formation. This study reports on lactoferrin,
      one of the substances released by neutrophils, and its effects on epithelial cell
      adhesion, growth, DNA synthesis and spreading of cell colonies at concentrations
      recorded in the crevicular fluid. We show that, in opposition to what has been
      reported on bacterial cells, lactoferrin has no effect on the DNA synthesis of
      attached epithelial cells in model systems attempting to simulate the DAT cells
      in vivo. However, both iron-saturated and unsaturated lactoferrin hampered cell
      adhesion, growth and spreading of cell colonies in a dose-dependent manner. These
      findings suggest that lactoferrin does not affect epithelial cell proliferation
      but it may have a role in delaying the repair of the DAT cell population during
      inflammation by interfering with cell adhesion.

PMID- 9524318
TI  - Localization and quantification of TXB2 in human healthy and inflammatory
      gingival mucosa.
AB  - We conducted a study to localize and quantify the thromboxane B2 (TXB2) in human
      gingival tissue obtained from clinically healthy sites and patients with
      gingivitis and periodontitis. Human gingival samples were assayed for TXB2 by
      immunofluorescence on slides and enzyme-immunoassay (EIA). We found that
      concentrations of TXB2 in gingivitis sites are at mean 10-fold higher than in the
      healthy sites and histologically show a consistently intracytoplasmic staining
      with a significant increase in gingivitis. This argues in favour of a local
      production of TXB2. Concentrations of TXB2 at periodontitis sites are only 3-fold
      higher than in healthy sites and histologically show a stronger staining as for
      the gingivitis sections, with principally an extracellular localization. Thus,
      TXB2 could be released in large quantities in the crevicular fluid when the
      periodontitis stage has reached. These data suggest that the epithelial cells of
      the gingival tissue are involved in synthesis and secretion of TXB2, which
      occurred during the development of gingival inflammation.

PMID- 9524317
TI  - Immunohistochemical demonstration of the plasminogen activator system in human
      gingival tissues and gingival fibroblasts.
AB  - The relative distribution of urokinase-type plasminogen activator (u-PA), tissue
      type plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1) and
      plasminogen activator inhibitor-2 (PAI-2) was studied in cultured human gingival
      fibroblasts, healthy gingival tissues and inflamed gingival tissues by
      immunohistochemistry. In cultured gingival fibroblasts t-PA, u-PA and PAI-1 were
      expressed in cytoplasm; u-PA and PAI-1 were more intensely stained than t-PA; PAI
      2 was not detectable in gingival fibroblasts. Following interleukin 1 beta (IL-1
      beta) stimulation, the intensity of intracellular staining for t-PA was increased
      and a number of cells staining strongly for PAI-2 were seen; no difference in the
      intensity of immunostaining level was noted for the expression of u-PA and PAI-1
      between IL-1 beta stimulated cells and unstimulated cells. In healthy gingival
      tissues, u-PA and PAI-1 displayed a wide distribution throughout all the
      connective tissue and epithelium; t-PA localized mainly in the connective tissue
      while PAI-2 showed little association with the connective tissue but did faintly
      stain in the epithelial layer. In inflamed gingival tissues, staining for t-PA
      was significantly increased in the extracellular matrix of the connective tissue,
      whereas staining for u-PA, PAI-1 and PAI-2 was found to be slightly increased,
      but no significant difference was noted for staining when compared with the
      healthy gingival tissues. A granular distribution of t-PA, u-PA, PAI-1 and PAI-2
      was noted around areas of inflammatory cell infiltration. These
      immunohistochemical findings indicate that the plasminogen activator system
      produced by fibroblasts may be influenced by the presence of the inflammatory
      mediator IL-1 beta. In addition, the significant increase of t-PA in inflamed
      connective tissue and the wide expression of these components around inflamed
      cells may contribute to connective tissue degradation and may relate to the
      migration and localization of monocytes/macrophages in inflamed tissue.

PMID- 9524319
TI  - The inhibition of DNA synthesis by prostaglandin E2 in human gingival fibroblasts
      is independent of the cyclic AMP-protein kinase A signal transduction pathway.
AB  - In this study we attempted to clarify the mechanism of the inhibitory effects of
      PGE2 on DNA synthesis in Gin-1 (fibroblasts derived from healthy human gingiva)
      from the aspect of the cyclic AMP-dependent protein kinase signal transduction
      pathway. PGE2 upregulated intracellular cyclic AMP accumulation and inhibited DNA
      synthesis in Gin-1 in a dose-dependent manner. When the PGE2-induced
      intracellular cyclic AMP accumulation was further enhanced by treatment with the
      cyclic AMP-phosphodiesterase inhibitor, IBMX, the inhibitory effect of PGE2 on
      DNA synthesis was also enhanced. Furthermore, when we examined the effects of
      forskolin, an activator of cyclic AMP production, on intracellular cyclic AMP
      accumulation and DNA synthesis, similar results were obtained. However,
      inhibitors of cyclic AMP-dependent protein kinase (protein kinase A) such as
      HA1004 did not diminish the inhibitory effect of PGE2 on DNA synthesis in Gin-1.
      These results suggest that in Gin-1, PGE2-induced cyclic AMP accumulation may not
      lead to the activation of protein kinase A or protein kinase A activity may not
      relate directly to the growth inhibitory effect of PGE2, and that PGE2 does not
      inhibit DNA synthesis through the cyclic AMP-protein kinase A signal transduction
      pathway in Gin-1.

PMID- 9524320
TI  - Gingival fibroblast response to cyclosporin A and transforming growth factor beta
      1.
AB  - This study investigates a potential role for TGF beta 1 in the pathogenesis of
      cyclosporin A-induced gingival overgrowth (CsA-OG). TGF beta 1 was localized
      immunohistochemically in the connective tissue of both normal gingiva and CsA-OG.
      Intense staining for TGF beta 1 was detected at the tips of the dermal papillae
      of the overgrown gingiva. In addition, fibroblasts derived from healthy gingiva
      and fibroblasts derived from CsA-OG were cultured both as monolayers or embedded
      in a 3D-collagen gel. Fibroblast activity was monitored in terms of protein and
      collagen production in the presence of (i) 1 ng/ml TGF beta 1, (ii) 500 ng/ml
      CsA, or (iii) 500 ng/ml CsA and 1 ng/ml TGF beta 1. In monolayer culture TGF beta
      1 significantly increased protein and collagen production in all cell strains (p
      < 0.05); however, there was no difference in response between fibroblasts from
      overgrown and healthy tissue. The production of both protein and collagen was
      significantly lower in the presence of the combination of CsA and TGF beta 1 when
      compared with the maximal stimulation produced by TGF beta 1 alone. In gel, TGF
      beta 1 significantly elevated matrix production by all overgrown cell strains (p
      < 0.05) but had little or no effect on the normal cell strains. The combination
      of CsA and TGF beta 1 in gel cultures reduced protein and collagen production by
      overgrown cell strains compared with TGF beta 1 alone. It is concluded that the
      cellular activity of gingival fibroblasts is dependent on culture conditions and
      that fibroblasts derived from overgrown gingival tissue are more responsive to
      TGF beta 1 than normal gingival fibroblasts when cultured in type I collagen gel.

PMID- 9524321
TI  - Eradication of Actinobacillus actinomycetemcomitans from the oral cavity in adult
      periodontitis.
AB  - Eradication of Actinobacillus actinomycetemcomitans from the oral cavity seems to
      be a prerequisite for successful therapeutic outcome in patients periodontally
      infected with the organism. In view of the limited number of subgingival samples
      obtained in recent studies one cannot conclude, however, whether eradication has
      actually been achieved. In the present study clinical and microbiological
      parameters were monitored in 10 adult patients with A. actinomycetemcomitans
      associated periodontitis during successive non-surgical and adjunctive
      metronidazole plus amoxicillin (or ciprofloxacin) (AB) therapy. In every patient,
      13 extracrevicular samples and subgingival samples from the deepest site of every
      tooth present were selectively cultivated for A. actinomycetemcomitans. The
      organism was isolated in 47 +/- 29% subgingival and 64 +/- 31% extracrevicular
      samples. Six weeks following subgingival scaling, A. actinomycetemcomitans was
      detected in 37 +/- 30% subgingival and 55 +/- 38% extracrevicular samples (n.s.).
      Three months after antibiotic therapy, the organism was recovered from only 1
      patient. At baseline, 7.5 +/- 4.2% sites had a probing pocket depth (PPD) > or =
      7 mm. This proportion dropped to 2.3 +/- 2.4% after scaling (p < 0.05) and to 0.3
      +/- 0.4% after AB (p < 0.05). The proportion of sites with clinical attachment
      loss (CAL) > or = 6 mm dropped from 23.3 +/- 13.3% to 17.7 +/- 13.4% (p < 0.05)
      and to 16.8 +/- 14.6%. Statistical analysis revealed that the organism was
      strongly related, at baseline, to PPD > or = 7 mm (odds ratio 9.8, p < 0.001).
      Six weeks after scaling, the organism was associated with CAL > or = 6 mm (odds
      ratio 1.8, p = 0.02). After scaling, high counts of A. actinomycetemcomitans in
      excess of 10(4) CFU/ml significantly interfered with attachment gain of > or = 2
      mm (odds ratio 0.24, p = 0.001). Based on the present findings, eradication of A.
      actinomycetemcomitans seems to be possible with adjunctive antibiotic treatment.
      Elimination of the organism after scaling was only weakly associated with
      clinical improvement.

PMID- 9524322
TI  - Rapid detection of Actinobacillus actinomycetemcomitans, Prevotella intermedia
      and Porphyromona gingivalis by multiplex PCR.
AB  - The identification of specific periodontal pathogens by conventional methods,
      mainly anaerobic cultivation, is difficult, time consuming and even sometimes
      unreliable. Therefore, a multiplex PCR method for simultaneous detection of
      Actinobacillus actinomycetemcomitans (A.a.), Porphyromona gingivalis (P.g.) and
      Prevotella intermedia (P.i.) was developed for rapid and easy identification of
      these specific bacterial pathogens in subgingival plaque samples. In this paper,
      there is a detailed description of the oligonucleotide primer selection, DNA
      extraction and PCR conditions and the sequencing of the amplified products. The
      locus chosen to be amplified is a highly variable region in the 16S ribosomal
      DNA. For the development of this technique ATCC cultures and pure cultures from
      subgingival plaque samples taken from periodontitis patients were used. As an
      internal positive control a recombinant plasmid was developed. This simple DNA
      extraction procedure and the DNA amplification and visualization of the amplified
      product permits the detection of the bacteria in a working day. Thus, this
      multiplex PCR method is a rapid and effective detection method for specific
      periodontal pathogens.

PMID- 9524323
TI  - EGF and IL-1 alpha modulate the release of collagenase, gelatinase and TIMP-1 as
      well as the release of calcium by rabbit calvarial bone explants.
AB  - Matrix metalloproteinases (MMPs), among which is collagenase (MMP-1), are likely
      to be involved in various steps of the bone resorption process. As both
      production of these enzymes and bone resorption appear to be mediated by
      cytokines, we investigated the effects of two cytokines, IL-1 alpha and EGF, on
      the release of collagenase, gelatinase A (MMP-2), gelatinase B (MMP-9), TIMP-1
      and calcium by rabbit calvariae. It was found that all these parameters increased
      under the influence of these cytokines. The release of calcium--used as a
      parameter of bone resorption--was highest in the combined presence of the
      cytokines. Although the absolute and relative enhancement by a combination of IL
      1 alpha and EGF was most pronounced for collagenase (7-fold), both gelatinase A
      (5-fold) and gelatinase B (1.5-fold) had increased simultaneously. Calvariae
      produced a high level of MMP inhibitor (TIMP-1), especially under the influence
      of the cytokines; periosteum released little inhibitor. It is concluded that IL-1
      alpha and EGF are likely to play a modulating role in the process of bone
      resorption.

PMID- 9524324
TI  - Magnetic resonance angiography of the hand and wrist: evaluation of patients with
      severe ischemic disease.
AB  - Conventional arteriography is considered the standard for the evaluation of
      patients with severe ischemic disease of the hand and wrist. Magnetic resonance
      (MR) has been shown to be a reliable noninvasive alternative to conventional
      arteriography. The authors prospectively evaluated this technology in 11 patients
      with Raynaud's syndrome and severe ischemic disease of the upper extremity. MR
      angiograms were compared with results from surgery in seven cases and
      conventional arteriography in four cases. There was excellent correlation between
      MR angiography and the results of surgery and conventional arteriography. In all
      cases, MR correctly predicted the patency or lack of patency of the distal and
      ulnar arteries, and superficial and deep palmar arches. In three cases, portions
      of the palmar arches oriented parallel to the plane were not adequately seen.
      Common and proper digital arteries were incompletely seen with both conventional
      and MR angiography. MR angiography is a reliable noninvasive method to evaluate
      patients with severe upper-extremity ischemic disease, accurately depicting the
      peripheral vessels through the level of the palmar arches. Anatomic vascular
      depiction is adequate for determination of patency of the major vessels for
      preoperative evaluation for reconstructive surgery and sympathectomy.

PMID- 9524325
TI  - Microvascular transfers in the treatment of massive long-bone osteomyelitis:
      filling the dugout canoe.

PMID- 9524326
TI  - Use of bilateral folded radial forearm free flaps for reconstruction of a midface
      gunshot wound.
AB  - Optimal treatment of midfacial gunshot wounds includes early definitive
      reconstruction of the bony scaffold to prevent soft tissue contraction. When this
      is not possible, secondary reconstruction is more difficult. The authors present
      a case of delayed reconstruction of a midface gunshot wound. Two months following
      a self-inflicted, submental gunshot wound and eventual rigid fixation of the
      remaining midfacial bony anatomy, two simultaneous radial forearm free flaps were
      utilized in the reconstruction. The first flap was folded onto itself to recreate
      the hard palate in conjunction with a split rib graft; the second flap filled the
      remaining soft-tissue defect and simultaneously provided lining for an eventual
      staged nasal reconstruction. The second stage of the nasal reconstruction was
      completed 5 weeks later with a calvarial bone graft and forehead flap. This dual
      microsurgical approach allowed for one-step reconstruction of both surfaces of
      the hard palate, resulting in separate oral and nasal cavities, and optimizing
      the patient's ability to speak and eat. Extensive soft-tissue contraction
      encountered in late reconstructions underscores the importance of an early,
      definitive, surgical approach in these difficult wounds.

PMID- 9524327
TI  - Acute pulmonary edema after microsurgery: two case reports.
AB  - Postoperative management procedures after microsurgery are well-established.
      Usually, maintaining an adequate plasma volume will lower blood viscosity and
      will provide an adequate arterial inflow to keep the replantation or the flap
      viable in routine microsurgical procedures. But if the patient's underlying
      condition is neglected, disasterous complications may occur. The authors report
      two cases with severe postoperative complications after microsurgery. One patient
      was a 38-year-old male who suffered from diabetic foot ulcer and received a free
      muscle flap transfer. He developed acute pulmonary edema at day 6
      postoperatively. The other patient was a 20-year-old pregnant woman at 31 weeks
      gestation who developed pulmonary edema on the POD 4 following microsurgical
      replantation of the thumb and index finger of her left hand. The complications
      were believed to be caused by fluid overload and neglect of the patients'
      underlying conditions. Knowledge of possible precipitating factors and careful
      monitoring of fluid should avoid acute pulmonary edema after microsurgery under
      certain unusual conditions.

PMID- 9524328
TI  - Reconstruction of skull defects with vascularized omentum transfer and split
      calvarial bone graft: two case reports.
AB  - Autogenous calvarial bone grafts have been widely used in craniofacial
      reconstruction following trauma, congenital anomalies, and head and neck tumors.
      In cases of late restoration of a collapsed cranial vault, an extradural dead
      space is occasionally observed which might cause infection and grafted bone
      absorption. The combined use of a split calvarial bone graft and an omental flap
      has been an effective technique for treating complicated cranial defects. The
      omental flap eliminates the extradural dead space between the grafted calvarial
      bone and the scarred dura, and provides an acceptable vascular bed for grafted
      bone. The authors report this technique for complex cranioplasties in two cases,
      with good cosmetic results.

PMID- 9524330
TI  - Z-plasty and microvascular anastomosis.
AB  - An experimental study in rats was designed to determine the effects of z-plasty
      on the patency of microvascular anastomosis. Eighty Sprague-Dawley rats of mixed
      sex were divided into two groups. In all animals, the left carotid arteries were
      used. In the first group (n = 40), a single z-plasty was done at the anterior
      side of the carotid artery before end-to-end anastomosis was performed. In the
      second group (n = 40), end-to-end anastomosis with interrupted sutures was done.
      Patency and the appearance of the anastomosis were evaluated 1 hr later, on the
      seventh postoperative day, and at the end of the third postoperative week. There
      was no vasospasm demonstrated in the first group. Patency rates were 100 percent
      for both groups after 1 hr. On the seventh postoperative day, one anastomosis in
      the first group (patency rate, 97.5 percent) and two anastomoses in the second
      group had failed (patency rate, 95 percent). Patency rates were similar at the
      third week. The difference was not statistically significant (p = 0.5).
      Histologic examinations demonstrated that z-plasty did not cause any adverse
      effects at the vessel wall or at the anastomosis.

PMID- 9524329
TI  - Selective neutrophil depletion with monoclonal antibodies attenuates
      ischemia/reperfusion injury in skeletal muscle.
AB  - The purpose of this study was to determine whether depletion of circulating
      neutrophils, using an antineutrophil monoclonal antibody (RP3), would attenuate
      ischemia/reperfusion injury in rat skeletal muscle. A 3- and 5-hr period of
      ischemia was induced unilaterally into the hindlimbs of rats; the isolated limbs
      were then reperfused for 24 hr after ischemia. The gastrocnemius muscle was then
      removed, and blood was taken simultaneously. The hematologic parameters were
      measured, muscle neutrophil sequestration was assessed by myeloperoxidase (MPO)
      activity, free radical production was evaluated by the tissue lipid peroxides
      (LPO) levels, muscle viability was assessed by tissue levels of adenosine
      triphosphate (ATP) and creatine phosphate (PCr) levels, and muscle wet/dry
      weights were determined. Treatment with RP3 selectively and sufficiently depleted
      the circulating neutrophil population, markedly reduced MPO, and significantly
      attenuated LPO and the tissue water content after both 3- and 5-hr of ischemia.
      After 3 hr of ischemia, ATP and PCr levels were significantly increased by
      neutrophil depletion; however, after 5 hr of ischemia, the same effect was not
      demonstrated. These results suggest that neutrophil depletion after 3 hr of
      ischemia restrains free radical production and edema formation, and also
      attenuates skeletal muscle ischemia reperfusion injury; however, after 5 hr of
      ischemia, ischemic damage was so severe, that neutrophil depletion did not reduce
      ischemia reperfusion injury.

PMID- 9524331
TI  - Venous flap ischemia: microcirculatory changes in experimental flaps in a rabbit
      model.
AB  - This study was designed to investigate the simultaneous changes in blood flow and
      microcirculation in an island flap during venous occlusion (venous ischemia), in
      an ischemia/reperfusion injury model in the rabbit. An island groin flap based on
      the inferior epigastric vessels was harvested in 15 rabbits. The flap was
      rendered ischemic for 3 hr (n = 5) or 4 hr (n = 10, 5 heparinized and 5 not), by
      applying a microvascular clamp to the inferior epigastric vein. Transonic Doppler
      and laser Doppler were used to monitor blood flow in the epigastric artery and
      microcirculation of the flap for 1 hr after flap elevation, 1 hr after occlusion,
      and for 3 hr at the end of the ischemic period. Venous occlusion was followed by
      a rapid decrease of blood flow and microcirculation readings. After ischemia,
      both blood flow and microcirculation readings in the flap were significantly
      decreased, compared to pre-ischemic values in all groups. In the 3-hr ischemia
      group, blood flow readings returned to pre-stress values, while microcirculation
      remained significantly lower. In the 4-hr ischemia group treated with heparin,
      blood flow in the artery settled at levels significantly lower than pre-stress
      readings; however, microcirculation of the flap was ultimately fully restored to
      pre-ischemic values. In the 4-hr ischemia group, both blood flow and
      microcirculation in the flap settled at levels significantly lower than pre
      stress values. The authors concluded that tolerance for venous ischemia is time
      dependent in this model and that venous ischemia is more deleterious than global
      ischemia. Administration of heparin may alter the time frame of
      ischemia/reperfusion injury and may prevent the harmful effects of injury at the
      microcirculatory level.

PMID- 9524332
TI  - Flap salvage in a "flow-through" flap by manual thrombectomy plus thrombolytic
      therapy.
AB  - A delay in identifying incipient flap failure may inevitably lead to complete
      pedicle thrombosis and the no-reflow phenomenon. The authors report a clinical
      case of a lateral arm free flap that suffered complete pedicle thrombosis. They
      successfully salvaged this flap, a type C fasciocutaneous "flow-through" flap, by
      manually moving the thrombus from proximal to distal in the main flap artery.
      This freed the septofasciocutaneous upward-perforating branches, by smoothing and
      applying firm pressure to the vessel, combined with thrombolytic therapy. Their
      technique is offered as an alternative procedure for salvaging a failing flow
      through flap.

PMID- 9524333
TI  - Long-term follow-up after finger and upper-limb replantation: clinical,
      angiologic, and lymphographic studies.
AB  - This 10-year follow-up study evaluates 25 patients with a total of 57
      successfully replanted fingers and six successfully replanted upper limbs. The
      global functional loss, including loss of range of motion, sensibility, and
      strength of the hand, was determined using the "Millesi score." The hemodynamic
      parameters of replanted and control fingers under resting and stress conditions
      were measured using a laser Doppler flowmeter. The lymphatic system at the site
      of replantation was examined by fluorescence microlymphography. All patients
      showed a considerable functional loss, according to the Millesi score, that
      averaged 56 percent of the normal function of the hand. In order to overcome
      functional deficit, many patients had developed successful compensatory
      mechanisms. In general, the patients themselves subjectively rated their
      functional deficits lower than indicated by the Millesi score. Laser Doppler
      flowmetry at rest and after arterial occlusion, and capillaroscopy before,
      during, and after a cold provocation test, revealed subnormal resting flow
      conditions and significantly decreased vascular capacity in the replanted
      fingers. Lymphatic drainage capacity was also significantly reduced despite
      documented reanastomosis between the skin microlymphatic network distal and
      proximal to the scar (fluorescence microlymphography). The coexistence of
      functional loss with compensatory mechanisms, decreased reactive hyperemia, and
      deficit in lymphatic drainage, present in all patients, must be considered as
      definitive sequelae of the initial injury.

PMID- 9524334
TI  - Free vascularized growth-plate transfer after bone tumor resection in children.
AB  - Limb-salvage surgery is the standard care for most malignant tumors affecting the
      extremities, and a vascularized fibula transfer is probably the most popular
      microsurgical option to reconstruct long-bone defects. Skeletal reconstruction
      after bone-tumor resection involving the metepiphysis of a growing child can be
      successfully achieved with a vascularized fibula graft incorporating the proximal
      physis and active growth plate. Such a procedure has been utilized in 12 children
      under the age of 10 years who had malignant bone tumors located in the upper limb
      (3 in the distal radius, 9 in the proximal humerus). The follow-up ranged between
      4 years and 3 months. Ten grafts were supplied by the anterior tibial artery, and
      two by the peroneal artery. The average growth rate of the grafts based on the
      former artery has been more than 1 cm per year, ranging between 0.75 and 1.33 cm.
      The authors describe a modified operative technique and discuss the clinical
      results of the procedure which offers a satisfactory skeletal reconstruction and
      prevents future limb-size discrepancy.

PMID- 9524335
TI  - Indicators of superior glenoid labral detachment on magnetic resonance imaging
      and computed tomography arthrography.
AB  - The magnetic resonance imaging and computed tomography arthrographic findings of
      36 shoulders with arthroscopically diagnosed detachment of the superior labrum
      were compared with those of 40 shoulders with a normal superior labrum to detect
      any findings specific to the injury. In this study we defined a specific magnetic
      resonance imaging finding as the presence of a linear, high-to-intermediate
      intensity area between the superior labrum and the glenoid rim on oblique coronal
      T2-weighted images. We also defined a specific computed tomography arthrography
      finding as air entering between the superior labrum and the upper part of the
      glenoid surface. On the basis of these findings magnetic resonance imaging had a
      sensitivity of 41%, a specificity of 86%, and an accuracy of 63%, whereas
      computed tomography arthrography had a sensitivity of 45%, a specificity of 93%,
      and an accuracy of 73%. Thus both of these procedures were specific for these
      particular findings, but they were neither sensitive nor accurate.

PMID- 9524336
TI  - Total shoulder replacement by magnetic arthroplasty.
AB  - Permanent magnets offer a novel solution to the problem of shoulder implant
      instability when the rotator cuff has been destroyed. We report a case of their
      use in a 66-year-old patient with a large proximal humerol breast cancer
      metastasis. Humerol resection was below the deltoid insertion. The polyacetal
      device had samarium-cobalt magnets in the humeral head. The glenoid component
      (the keeper in the magnetic circuit) was made of titanium nitride-coated F17
      stainless steel. The system's breakaway force was ca. 40 N. At 24 months the
      shoulder was free of pain and stable, with an active range of movement of 30
      degrees flexion, 45 degrees external rotation, and internal rotation to T8. The
      patient could perform household tasks and drive an automatic car. Radiography
      showed no implant loosening or upward humeral head dislocation. Subsequently, the
      patient's condition deteriorated; at 33 months she was bedridden, and radiography
      showed dislocation of the humeral component.

PMID- 9524337
TI  - Posterolateral elbow joint instability: the basic kinematics.
AB  - Thirty-five osteoligamentous elbows were included in a study on the kinematics of
      posterolateral elbow joint instability during the pivot shift test (PST) before
      and after separate ligament cuttings in the lateral collateral ligament complex
      (LCLC). Division of the annular ligament or the lateral ulnar collateral ligament
      caused no laxity during the PST. Division of the lateral collateral ligament
      caused maximal laxity of 4 degrees and 23 degrees during forced PST in valgus and
      external rotation (supination), respectively. Cutting of the LCLC at the ulnar or
      the humeral insertion was necessary for any PST stressed elbow joint laxity to
      occur. Total division of the LCLC induced a maximal laxity of 7.9 degrees and 37
      degrees during forced PST in valgus and external rotation (supination),
      respectively. This study suggests the lateral collateral ligament to be the
      primary soft tissue constraint to PST stress and the annular ligament and the
      lateral ulnar collateral ligament to be only secondary constraints. This study
      indicates that the integrity of the medial collateral elbow ligaments should be
      evaluated during forced valgus in pronation or neutral forearm rotation.
      Furthermore an isometric lateral collateral ligament reconstruction was shown to
      correct the joint laxity introduced by total LCLC transection.

PMID- 9524338
TI  - Arthroscopic treatment of calcific tendinitis of the shoulder.
AB  - We evaluated 48 patients arthroscopically treated for calcific tendinitis. All
      patients' were treated by removal of the calcific deposit whenever possible and
      resection of the coracoacromial ligament. Those cases showing evidence of
      subacromial stenosis by x-ray evaluation or intraoperative findings were treated
      with an arthroscopic arcromioplasty during the same procedure. For postoperative
      functional assessment we used the Constant score. After surgery the Constant
      score significantly improved. All patients who were treated by acromioplasty
      showed significant flattening of the bony configuration of the acromion. The x
      ray review showed that none of the blurred calcific deposits regained sharper
      borders after operation and also that no transparent deposit was converted into a
      denser appearance after the procedure. Those patients with postoperative
      elimination or reduction of the calcific deposits had significantly better
      outcomes than those who had no radiographic change. Acromioplasty did not improve
      the results. The aim of arthroscopic treatment in calcific tendinitis is to
      remove the calcific deposit.

PMID- 9524339
TI  - Release of ulnar nerve compression at the elbow through a transverse incision.
AB  - The purpose of this study was to modify the classical longitudinal skin incision
      to avoid injury to the cutaneous nerve branches on the medial side of the elbow
      when a surgical release of the ulnar nerve was performed. Injury to the medial
      antebrachial cutaneous nerve is not a rare complication after release of the
      ulnar nerve at the elbow. This will leave an area of hyposthesia on the
      posteromedial aspect of the proximal forearm, to which the patient will usually
      get accustomed. Some patients may have an area of skin dysesthesia and a painful
      amputation neuroma requiring surgical treatment. To avoid these complications and
      yet to obtain adequate exposure for ulnar nerve release, we have used a
      transverse incision in 20 patients without any sequelae of hyposthesia or
      amputation neuromas and have attained a far superior esthetic result.

PMID- 9524340
TI  - Dynamic glenohumeral joint stability.
AB  - Stability of the glenohumeral joint with an anterior, posterior, and inferior
      displacement force of 50 N was measured in a dynamic shoulder model. Controlled
      hydrodynamic actuator forces were applied to the deltoid muscle and to the
      rotator cuff in seven anatomic specimens. During elevation of the arm the
      position of the humerus was measured with a six-degree-of-freedom ultrasonic
      sensor device. The rotational center of the humeral head was used as a reference
      point for translation. A displacement force of 50 N led to significant humeral
      head displacement anteriorly and posteriorly but not inferiorly. A 50% reduction
      of rotator cuff forces increased anterior displacement by 46% and posterior
      displacement by 31%. Venting of the glenohumeral joint space and of the
      subacromial bursa resulted in a 50% increase of anterior displacement, a 19%
      increase of posterior displacement, and significant inferior displacement. This
      study demonstrates that in addition to passive stabilizers and negative
      intraarticular pressure, rotator cuff force significantly contributes to
      stabilization of the glenohumeral joint during arm motion. Muscle strength and
      coordination should gain more emphasis in the diagnosis and treatment of shoulder
      instability.

PMID- 9524341
TI  - Surgical treatment of acute and chronic posterior fracture-dislocation of the
      shoulder.
AB  - Seventy-three shoulders (66 patients) with posterior fracture-dislocation of the
      shoulder were treated. Thirty patients were treated during the acute phase. One
      case was classified as subspinous, and 56 were considered subacromial; 4 cases
      had posterior fracture-dislocation in three parts, 3 in four parts, and 9 at the
      anatomic neck. Treatment consisted of closed reduction and immobilization in the
      emergency department, McLaughlin's procedure, hemiarthroplasty, total shoulder,
      open reduction with internal fixation, arthroplastic resection, and arthrodesis.
      Ten shoulders were treated conservatively. The University of California-Los
      Angeles rating score was used to analyze 56 shoulders during a mean follow-up
      period of 32.7 months. Good and excellent results can be achieved in those cases
      that are treated up to 2 years of the lesion; after 2 years results tend to be
      fair. We do not suggest total shoulder arthroplasty as a treatment option for
      those surgeons without the necessary expertise.

PMID- 9524342
TI  - Developmental anterior dislocation of the radial head caused by solitary
      osteochondroma of the proximal ulna.

PMID- 9524343
TI  - Pigmented villonodular synovitis of the elbow.
AB  - Pigmented villonodular synovitis (PVNS) is a monoarticular condition with a
      variable prognosis. The first account of it was given by Chassaignac in 1852. The
      condition was given its name by Jaffe in 1941. In separate studies Miller in 1982
      and Flandry et al. in 1994 determined the overall incidence of PVNS varied
      between 1 and 3 per 1,000,000. The joint most commonly involved is the knee, and
      according to Dorwart et al. the elbow is rarely affected. Seventeen other cases
      of PVNS of the elbow have been reported, and very scant information exists about
      optimal treatment or outcome.

PMID- 9524344
TI  - A fracture-dislocation of the lateral end of the clavicle in a 14-year-old boy.

PMID- 9524345
TI  - Quadrilateral space syndrome caused by a ganglion.

PMID- 9524346
TI  - Cost of modular shoulder arthroplasty.

PMID- 9524347
TI  - Managing attribute--value clinical trials data using the ACT/DB client-server
      database system.
AB  - ACT/DB is a client-server database application for storing clinical trials and
      outcomes data, which is currently undergoing initial pilot use. It stores most of
      its data in entity-attribute-value form. Such data are segregated according to
      data type to allow indexing by value when possible, and binary large object data
      are managed in the same way as other data. ACT/DB lets an investigator design a
      study rapidly by defining the parameters (or attributes) that are to be gathered,
      as well as their logical grouping for purposes of display and data entry. ACT/DB
      generates customizable data entry. The data can be viewed through several
      standard reports as well as exported as text to external analysis programs.
      ACT/DB is designed to encourage reuse of parameters across multiple studies and
      has facilities for dictionary search and maintenance. It uses a Microsoft Access
      client running on Windows 95 machines, which communicates with an Oracle server
      running on a UNIX platform. ACT/DB is being used to manage the data for seven
      studies in its initial deployment.

PMID- 9524348
TI  - A comparison of nursing minimal data sets.
AB  - It is often argued that Nursing Minimal Data Sets (NMDSs) have advantages for the
      nursing profession. The NMDSs that have been developed and applied in some
      countries have many features in common, but there are differences in purpose,
      content, sampling, collection approach, and developmental stage as well. This
      paper examines the advantages and disadvantages of data sets of nursing practice,
      and the differences and similarities of five national and international NMDS
      systems. The purpose is to apply this information toward an NMDS initiative in
      the Netherlands. Future initiatives in NMDS development should include
      international coordination.

PMID- 9524350
TI  - Participatory design of information systems in health care.
AB  - AIM: To study the objectives, processes, and ideologies expressed during
      participatory design of information systems (PDIS) in health care. DESIGN:
      Longitudinal documentation of project meetings by video recording. Grounded
      theory development in three steps. SETTING: Systems development project in
      primary care. RESULTS: The developing system was discussed mainly from a clinical
      and practical, as opposed to a technical, viewpoint. The design decisions were
      related to societal-level participants and institutions. This external influence
      on design decisions was mediated by design voices in discussions, each having its
      own scope. CONCLUSIONS: The social environment has to be considered when applying
      PDIS in health care. Instructions for nondesigners can be used to introduce them
      to the design objectives, processes, and ideologies on which PDIS is based and to
      support them when relating clinical and practical design questions to the
      existing social constraints and norms.

PMID- 9524351
TI  - Development of a hospital information system using the TAD method.
AB  - OBJECTIVE: To examine the capability of a new object-oriented method called
      Tabular Application Development (TAD) in developing a hospital information system
      for a gastroenterology clinic. DESIGN: TAD has five phases. The first phase
      identifies the problem to be solved. The second phase defines the business
      processes and activities involved. The third phase develops the object model. The
      fourth phase designs the application model. The final phase deals with
      implementation. RESULTS: Eight requirements for the system were identified by
      hospital management; 17 specific tasks were grouped into three activity
      categories. The process model, the object model, and the application model of the
      system are described. CONCLUSION: The TAD method is capable of developing such an
      information system without any problem. Furthermore, the method minimizes the
      time needed to do this in such a way that the process is completely visible to
      the analyst.

PMID- 9524349
TI  - Development and initial validation of an instrument to measure physicians' use
      of, knowledge about, and attitudes toward computers.
AB  - This paper describes details of four scales of a questionnaire-- "Computers in
      Medical Care"--measuring attributes of computer use, self-reported computer
      knowledge, computer feature demand, and computer optimism of academic physicians.
      The reliability (i.e., precision, or degree to which the scale's result is
      reproducible) and validity (i.e., accuracy, or degree to which the scale actually
      measures what it is supposed to measure) of each scale were examined by analysis
      of the responses of 771 full-time academic physicians across four departments at
      five academic medical centers in the United States. The objectives of this paper
      were to define the psychometric properties of the scales as the basis for a
      future demonstration study and, pending the results of further validity studies,
      to provide the questionnaire and scales to the medical informatics community as a
      tool for measuring the attitudes of health care providers. METHODOLOGY: The
      dimensionality of each scale and degree of association of each item with the
      attribute of interest were determined by principal components factor analysis
      with orthogonal varimax rotation. Weakly associated items (factor loading < .40)
      were deleted. The reliability of each resultant scale was computed using
      Cronbach's alpha coefficient. Content validity was addressed during scale
      construction; construct validity was examined through factor analysis and by
      correlational analyses. RESULTS: Attributes of computer use, computer knowledge,
      and computer optimism were unidimensional, with the corresponding scales having
      reliabilities of .79, .91, and .86, respectively. The computer-feature demand
      attribute differentiated into two dimensions: the first reflecting demand for
      high-level functionality with reliability of .81 and the second demand for
      usability with reliability of .69. There were significant positive correlations
      between computer use, computer knowledge, and computer optimism scale scores and
      respondents' hands-on computer use, computer training, and self-reported computer
      sophistication. In addition, items posited on the computer knowledge scale to be
      more difficult generated significantly lower scores. CONCLUSION: The four scales
      of the questionnaire appear to measure with adequate reliability five attributes
      of academic physicians' attitudes toward computers in medical care: computer use,
      self-reported computer knowledge, demand for computer functionality, demand for
      computer usability, and computer optimism. Results of initial validity studies
      are positive, but further validation of the scales is needed. The URL of a
      downloadable HTML copy of the questionnaire is provided.

PMID- 9524352
TI  - Simulating an integrated critiquing system.
AB  - OBJECTIVE: To investigate factors that determine the feasibility and
      effectiveness of a critiquing system for asthma/COPD that will be integrated with
      a general practitioner's (GP's) information system. DESIGN: A simulation study.
      Four reviewers, playing the role of the computer, generated critiquing comments
      and requests for additional information on six electronic medical records of
      patients with asthma/COPD. Three GPs who treated the patients, playing users,
      assessed the comments and provided missing information when requested. The GPs
      were asked why requested missing information was unavailable. The reviewers
      reevaluated their comments after receiving requested missing information.
      MEASUREMENTS: Descriptions of the number and nature of critiquing comments and
      requests for missing information. Assessment by the GPs of the critiquing
      comments in terms of agreement with each comment and judgment of its relevance,
      both on a five-point scale. Analysis of causes for the (un-)availability of
      requested missing information. Assessment of the impact of missing information on
      the generation of critiquing comments. RESULTS: Four reviewers provided 74
      critiquing comments on 87 visits in six medical records. Most were about
      prescriptions (n = 28) and the GPs' workplans (n = 27). The GPs valued comments
      about diagnostics the most. The correlation between the GPs' agreement and
      relevance scores was 0.65. However, the GPs' agreements with prescription
      comments (complete disagreement, 31.3%; disagreement, 20.0%; neutral, 13.8%;
      agreement, 17.5%; complete agreement, 17.5%) differed from their judgments of
      these comments' relevance (completely irrelevant, 9.0%; irrelevant, 24.4%;
      neutral, 24.4%; relevant, 32.1%; completely relevant, 10.3%). The GPs were able
      to provide answers to 64% of the 90 requests for missing information. Reasons
      available information had not been recorded were: the GPs had not recorded the
      information explicitly; they had assumed it to be common knowledge; it was
      available elsewhere in the record. Reasons information was unavailable were: the
      decision had been made by another; the GP had not recorded the information. The
      reviewers left 74% of the comments unchanged after receiving requested missing
      information. CONCLUSION: Human reviewers can generate comments based on
      information currently available in electronic medical records of patients with
      asthma/COPD. The GPs valued comments regarding the diagnostic process the most.
      Although they judged prescription comments relevant, they often strongly
      disagreed with them, a discrepancy that poses a challenge for the presentation of
      critiquing comments for the future critiquing system. Requested additional
      information that was provided by the GPs led to few changes. Therefore, as system
      developers faced with the decision to build an integrated, non-inquisitive or an
      inquisitive critiquing system, the authors choose the former.

PMID- 9524354
TI  - Presentation of the Morris F. Collen Award to Donald A. B. Lindberg, MD.

PMID- 9524353
TI  - Evaluation of a "lexically assign, logically refine" strategy for semi-automated
      integration of overlapping terminologies.
AB  - OBJECTIVE: To evaluate a "lexically assign, logically refine" (LALR) strategy for
      merging overlapping healthcare terminologies. This strategy combines description
      logic classification with lexical techniques that propose initial term
      definitions. The lexically suggested initial definitions are manually refined by
      domain experts to yield description logic definitions for each term in the
      overlapping terminologies of interest. Logic-based techniques are then used to
      merge defined terms. METHODS: A LALR strategy was applied to 7,763 LOINC and
      2,050 SNOMED procedure terms using a common set of defining relationships taken
      from the LOINC data model. Candidate value restrictions were derived by lexically
      comparing the procedure's name with other terms contained in the reference SNOMED
      topography, living organism, function, and chemical axes. These candidate
      restrictions were reviewed by a domain expert, transformed into terminologic
      definitions for each of the terms, and then algorithmically classified. RESULTS:
      The authors successfully defined 5,724 (73%) LOINC and 1,151 (56%) SNOMED
      procedure terms using a LALR strategy. Algorithmic classification of the defined
      concepts resulted in an organization mirroring that of the reference hierarchies.
      The classification techniques appropriately placed more detailed LOINC terms
      underneath the corresponding SNOMED terms, thus forming a complementary
      relationship between the LOINC and SNOMED terms. DISCUSSION: LALR is a successful
      strategy for merging overlapping terminologies in a test case where both
      terminologies can be defined using the same defining relationships, and where
      value restrictions can be drawn from a single reference hierarchy. Those concepts
      not having lexically suggested value restrictions frequently indicate gaps in the
      reference hierarchy.

PMID- 9524355
TI  - Collagen biosynthesis: a mini-review cluster.

PMID- 9524356
TI  - Prolyl 4-hydroxylases and their protein disulfide isomerase subunit.
AB  - Prolyl 4-hydroxylases (EC 1.14,11.2) catalyze the formation of 4-hydroxyproline
      in collagens and other proteins with collagen-like sequences. The vertebrate type
      I and type II enzymes are [alpha (I)]2 beta 2 and [alpha (II)]2 beta 2 tetramers,
      respectively, whereas the enzyme from the nematode Caenorhabditis elegans is an
      alpha beta dimer. The type I enzyme is the major form in most but not all
      vertebrate tissues. The catalytic properties of the various enzyme forms are
      highly similar, but there are distinct, although small, differences in K(m)
      values for various peptide substrates between the enzyme forms and major
      differences in Ki values for the competitive inhibitor, poly(L-proline). Prolyl 4
      hydroxylase requires Fe2+, 2-oxoglutarate, O2 and ascorbate. Kinetic studies and
      theoretical considerations have led to elucidation of the reaction mechanism, and
      recent extensive site-directed mutagenesis studies have identified five critical
      residues at the cosubstrate binding sites. A number of compounds have been
      characterized that inhibit it competitively with respect to some of the
      cosubstrates, and three groups of suicide inactivators have also been identified.
      The beta subunit in all forms of prolyl 4-hydroxylase is identical to protein
      disulfide isomerase (PDI), a multifunctional polypeptide that also serves as a
      subunit in the microsomal triglyceride transfer protein, as a chaperone-like
      polypeptide that probably assists folding of a number of newly synthesized
      proteins, and in several other functions. The main role of the PDI polypeptide as
      a protein subunit is probably related to its chaperone function. Recent
      expression studies of recombinant human prolyl 4-hydroxylase subunits in a yeast
      have indicated that the formation of a stable enzyme tetramer in vivo requires
      coexpression of collagen polypeptide chains.

PMID- 9524357
TI  - Molecular recognition in procollagen chain assembly.
AB  - Recent advances in the understanding of the molecular recognition events
      occurring during the assembly of procollagen during biosynthesis have come from
      the use of a semi-permeabilized cell-system that reconstitutes the initial steps
      of chain assembly as they would occur in the endoplasmic reticulum of an intact
      cell. This has enabled a number of key questions concerning the molecular
      determinants of procollagen assembly to be addressed. In particular, the
      recognition events underlying the initial association of individual procollagen
      chains have been investigated, resulting in the identification of the key
      residues involved within the C-propeptide of fibrillar collagens. Similarly, the
      role of inter-chain disulfide bond formation in chain recognition and assembly
      has been investigated, along with the role of the C-propeptide, C-telopeptide and
      proline hydroxylation in helix nucleation, alignment and propagation. The results
      from these studies point to a two-stage recognition event, i.e., association of
      the chains driven by residues within the C-propeptide followed by nucleation and
      alignment of the helix driven mainly by sequences present at the C-terminal end
      of the triple helical domain.

PMID- 9524358
TI  - Expression and function of heat shock protein 47: a collagen-specific molecular
      chaperone in the endoplasmic reticulum.
AB  - Heat shock protein (HSP) 47 is a collagen-binding stress protein localized in the
      endoplasmic reticulum (ER). In addition to stress-inducibility through heat shock
      element-heat shock factor interaction, the expression of HSP47 under normal
      conditions always correlates with that of collagens in various cell types and
      tissues. Both HSP47 and types I and III collagens are also dramatically induced
      under pathophysiological conditions such as liver fibrosis. HSP47 transiently
      associates with procollagen in the ER and dissociates from it in the cis-Golgi
      compartment. Possible functions of HSP47 as a molecular chaperone specific for
      procollagen are discussed: prevention of nascent procollagen chains from forming
      aggregates, effect on the modification of procollagen, inhibition of
      intracellular degradation of procollagen, quality control mechanisms under stress
      conditions, and effect on the secretion from the ER to the Golgi compartment.

PMID- 9524360
TI  - Procollagen N-proteinase and procollagen C-proteinase. Two unusual
      metalloproteinases that are essential for procollagen processing probably have
      important roles in development and cell signaling.
AB  - As soon as procollagen precursors of fibrillar collagens were discovered in the
      early 1970s, it became apparent that connective tissues must contain proteolytic
      activities that cleave the N-propeptides and the C-propeptides from procollagens.
      Isolation and characterization of the enzymic activities, however, proved to be
      unexpectedly difficult. Both proteinases are large and are synthesized in several
      different forms with polypeptide chains ranging in size from 70 kDa to about 130
      kDa. The N-proteinase has the unusual property of cleaving the N-propeptides from
      type I and type II procollagens if the proteins are in a native conformation, but
      not if the proteins are partially unfolded so that the N-telopeptides are no
      longer in a hair-pin configuration. The C-proteinase specifically cleaves native
      and denatured types I, II and III procollagens. It also specifically cleaves a
      precursor of lysyl oxidase and laminin 5. Both enzymes and their variants have
      structures that place them in a large and expanding super-family of over 200 zinc
      binding metalloproteinases. The larger of two forms of the N-proteinase contains
      an RGD sequence for binding through integrins and properdin repeats similar to
      those found in thrombospondin. The shorter 70 kDa form of the C-proteinase is
      identical to the protein that was previously identified as bone morphogenic
      protein-1. Both the 70 kDa C-proteinase and two larger forms are homologous to
      proteins that are expressed early in development in a variety of organisms,
      including Drosophila, sea urchin, and fish. Therefore, the data suggest that both
      the N- and C-proteinases have important biological functions in addition to the
      roles in the processing of procollagens.

PMID- 9524359
TI  - Lysyl oxidase: properties, regulation and multiple functions in biology.
AB  - Lysyl oxidase (LO) is a copper-dependent amine oxidase that plays a critical role
      in the biogenesis of connective tissue matrices by crosslinking the extracellular
      matrix proteins, collagen and elastin. Levels of LO increase in many fibrotic
      diseases, while expression of the enzyme is decreased in certain diseases
      involving impaired copper metabolism. While the three-dimensional structure of
      the enzyme is not yet available, many of its physical-chemical properties, its
      novel carbonyl cofactor, and its catalytic mechanism have been described. Lysyl
      oxidase is synthesized as a preproprotein, secreted as a 50 kDa, N-glycosylated
      proenzyme and then proteolytically cleaved to the 32 kDa, catalytically active,
      mature enzyme. Within the past decade, the gene encoding LO has been cloned,
      facilitating investigations of the regulation of expression of the enzyme in
      response to diverse stimuli and in numerous disease states. Transforming growth
      factor-beta, platelet-derived growth factor, angiotensin II, retinoic acid,
      fibroblast growth factor, altered serum conditions, and shear stress are among
      the effectors or conditions that regulate LO expression. New, LO-like genes have
      also been identified and cloned, suggesting the existence of a multigene family.
      It has also become increasingly evident that LO may have other important
      biological functions in addition to its role in the crosslinking of elastin and
      collagen in the extracellular matrix.

PMID- 9524361
TI  - Type I collagen synthesis in cultured human fibroblasts: regulation by cell
      spreading, platelet-derived growth factor and interactions with collagen fibers.
AB  - Type I collagen protein and pro-alpha 1(I) collagen mRNA levels were investigated
      in human dermal fibroblasts cultured on substrates which induced distinct
      morphologies. Induction of type I collagen protein synthesis required cell
      spreading in monolayer cultures; mere attachment to dishes coated with 2
      hydroxyethyl methacrylate (poly(HEMA)) did not suffice. Spread cells or round
      cells cultured on poly(HEMA) differed in collagen type I production, but pro
      alpha 1(I) collagen mRNA levels were similar. Recombinant human platelet-derived
      growth factor (PDGF)-BB could replace cell spreading as a stimulus for collagen
      synthesis in cells cultured on poly(HEMA). At later time points, pro-alpha 1(I)
      collagen mRNA levels were down-regulated, although relatively less than type I
      collagen synthesis. Type I collagen synthesis by fibroblasts cultured in three
      dimensional collagen gels was strongly down-regulated at both the protein and RNA
      levels. In addition to its capacity to stimulate collagen synthesis, PDGF-BB
      induced elongation and the formation of long processes by fibroblasts cultured in
      collagen gels. The stimulatory effect by cell spreading and PDGF-BB on collagen
      synthesis was inhibited by the phosphatidylinositol 3-kinase (PI3K) inhibitor
      LY294002. However, inhibition of PI3K only inhibited induction of collagen
      synthesis by actively spreading cells or by PDGF-BB and did not induce a down
      regulation of collagen synthesis in cells which had already spread. These data
      demonstrate that type I collagen protein synthesis is partly independent of pro
      alpha 1(I) collagen mRNA levels but highly regulated by cell shape, although this
      could be decoupled by PDGF-BB. Both cell shape- and PDGF-BB-induced stimulation
      of collagen type I synthesis depends on a signalling pathway involving PI3K.
      Furthermore, levels of pro-alpha 1(I) collagen mRNA in fibroblasts are partly
      cell shape independent but are down-regulated by fibroblast interactions with
      native collagen fibers.

PMID- 9524362
TI  - Alternative splicing of VWFA modules generates variants of type VI collagen alpha
      3 chain with a distinctive expression pattern in embryonic chicken tissues and
      potentially different adhesive function.
AB  - Type VI collagen, a ubiquitous extracellular cell adhesion molecule, is formed by
      heterotrimeric monomers which associate into dimers and tetramers and assemble
      into larger oligomers constituting the 100 nm-long periodic microfilaments of
      connective tissues. One distinctive structural characteristic of type VI collagen
      is represented by an alpha 3 chain with a much larger molecular mass compared to
      the other two chains and with an extensive size heterogeneity, exemplified by the
      separation into up to five polypeptides in SDS-PAGE. There is evidence that the
      alpha 3(VI) mRNA can undergo alternative splicing of three VWFA modules at the 5'
      end, potentially resulting in the expression of protein variants. Here we report
      that alternative splicing of alpha 3(VI) mRNA in chicken embryo did not result in
      the absolute predominance of a particular alpha 3(VI) form in any tissue;
      instead, the expression of variants including exons A9, A8 and A6 increased with
      age. In addition, these variants had a more restricted tissue distribution
      pattern compared to variants including only constitutive exons: A9+ were the
      rarest and were present almost exclusively in skin and skeletal muscle; A6+ were
      expressed in several of the examined tissues with local variations; A8+ had
      intermediate levels and were less widely distributed than A6+ variants.
      Quantitative densitometric scanning of immunoblots of type VI collagen purified
      from gizzard and stained with VWFA module-specific antibodies indicated that the
      polymorphic migration pattern of alpha 3(VI) polypeptides is contributed by
      concurrent or independent splicing of two exons (A8 and A6) and probably by
      processing and/or proteolysis at the N- and C-terminus. Three exon-specific
      recombinant polypeptides were examined in cell adhesion assays, and A6 appeared
      to be the most active, particularly at low substrate concentrations. The adhesion
      to the recombinant modules was not abrogated by EDTA nor by mAbs against the
      integrin beta 1 or alpha 2 subunits. Over all, these results suggest that the
      splicing of the alpha 3(VI) mRNA and the tissue distribution pattern of type VI
      collagen variants, apart from promoting cell adhesion to different extents, might
      also affect additional structural as well as functional properties of this
      molecule, including microfilament formation and interaction with other
      extracellular matrix molecules.

PMID- 9524363
TI  - Evidence of fraud.

PMID- 9524364
TI  - Fraud perpetration on a larger scale.

PMID- 9524367
TI  - Occupational back pain.

PMID- 9524365
TI  - Coeliac diagnosis in childhood.

PMID- 9524368
TI  - Advances in periodontal diagnosis. 3. Assessing potential biomarkers of
      periodontal disease activity.
AB  - The methods for assessing potential biomarkers of periodontal disease activity
      are considered. This is necessary because a detailed examination of all the
      relevant research evidence is an essential process in assessing the possible
      clinical usefulness of a periodontal diagnostic test system based on any one of
      these markers.

PMID- 9524369
TI  - The dental practitioner's role in protecting children from abuse. 3. Reporting
      and subsequent management of abuse.
AB  - The third and final article of the series covers the mechanism a general dental
      practitioner should follow when alerting the authorities to a child at risk, and
      the subsequent investigations and actions that follow such a report.

PMID- 9524370
TI  - Tooth wear in adolescents requires further investigation.

PMID- 9524372
TI  - An effective strategy for the transfer of children from the CDS to the GDS.

PMID- 9524373
TI  - The prevalence of tooth wear in a cluster sample of adolescent schoolchildren and
      its relationship with potential explanatory factors.
AB  - OBJECTIVE: To assess the prevalence of tooth wear in adolescents and its
      relationship with diet, saliva and gastro-oesophageal reflux. DESIGN: Single
      centre cluster sample epidemiological study. SETTING: A school in London in the
      summer of 1996. SUBJECTS: 11-14-year-old schoolchildren. MAIN OUTCOME MEASURES:
      The Smith and Knight tooth wear index (TWI), salivary factors, diet and symptoms
      of gastro-oesophageal reflux were recorded for all subjects. RESULTS: Results
      were obtained from 210 subjects. One subject refused to provide a saliva sample
      and 11 subjects provided insufficient saliva for analysis of buffering power (n =
      198). 57% (95% confidence intervals 50.3-63.7%) of subjects had tooth wear on
      more than ten teeth and a median 12% (interquartile range 6-18%, 95% confidence
      intervals 8-14%) of surfaces were affected. However, dentine involvement was
      rare. The median intake of carbonated drinks was 2 cans (interquartile range 1-3)
      a day. However, there was no correlation with TWI (r = -0.09, P = 0.19). There
      was no relationship between tooth wear index (TWI) and salivary flow rate (r = 
      0.02, P = 0.78) or buffering capacity (r = -0.02, P = 0.76). A trend was observed
      for those with a reported history of regurgitation (n = 27) to have a higher
      maxillary TWI (median 8, interquartile range 2-13) compared with those who did
      not (5, 2-9, P = 0.06). CONCLUSIONS: Tooth wear is common in adolescents and the
      relationship with dietary acid, salivary buffering and symptoms of gastro
      oesophageal reflux is complex and requires further investigation.

PMID- 9524374
TI  - Dental negligence: a study of cases assessed at one specialised advisory
      practice.
AB  - AIM: To undertake a review of cases from one dental advisory practice in England
      over a period of 5.5 years to provide a profile of the type of work undertaken.
      DESIGN AND SETTING: Compensation claims for dental negligence seen at one dental
      advisory practice between 1991 and 1996. METHODS: 437 claims were reviewed for:
      the nature of the complaint; defendant details; plaintiff details; method of
      funding; duration and outcome of claim. Comparisons were made with previously
      published data. The relationship between method of funding of a claim and the
      likelihood of the claim being successful was investigated. RESULTS: 28% of
      complaints concerned oral surgery and 24%, restorative procedures. In 72% of
      cases, the compensation claim was made directly against the dentist who had
      provided treatment for the patient. The majority of claims were gender and age
      biased; females (63%) and younger people (18-45 years of age) (68%) were more
      likely to bring actions for dental negligence. Only 3% involved elderly patients
      (> or = 60 years old). Claims supported by the government legal aid scheme were
      more likely to be withdrawn or rejected than those privately funded. Nearly all
      cases were completed in under one year (81%). CONCLUSIONS: Results are similar to
      previously published studies. A large proportion of claims concerned restorative
      or oral surgery procedures carried out in general or community practice.

PMID- 9524375
TI  - The transfer of child patients from the community dental service to the general
      dental service.
AB  - OBJECTIVE: To determine an effective strategy for the transfer of children from
      the CDS to the GDS. DESIGN: Single centre study comprising a retrospective
      analysis of a 50% random sample of dental records for children transferred from
      CDO to GDP. SETTING: Community dental clinic in an urban area of south Manchester
      with relatively little material deprivation. SUBJECTS AND METHODS: Between 1990
      and 1995, a GDP worked up to 5 hours a week in the CDS clinic seeing routine
      child patients referred by the CDO. MAIN OUTCOME MEASURES: Numbers of children
      registered with a GDP after varying periods of time. Attendance records of
      children transferred from CDS to GDS and rates of failed appointments. RESULTS:
      After 4 1/2 years, 264 child patients had been registered with the GDP under
      capitation and a further 55 adults were registered under continuing care. The
      majority of children had retained registration for more than 2 1/2 years. The
      mean rate of failed appointments was 16%. CONCLUSION: Children can be transferred
      successfully from the CDS to the GDS if the GDP works at the community clinic and
      there are further benefits which accrue to the scheme.

PMID- 9524376
TI  - Audit activity and uptake of postgraduate dental education among general dental
      practitioners in Yorkshire.
AB  - The aim of this study was to assess the involvement of general dental
      practitioners in Yorkshire in clinical audit activity and in postgraduate dental
      education and to compare the results with those of a previous survey undertaken
      in 1989. There is a need to find ways of encouraging all general dental
      practitioners to become actively involved in continuing professional development
      and in improving the quality of general dental practice through the use of
      clinical audit.

PMID- 9524377
TI  - The future of psychiatry: communities in action.
AB  - Psychiatry and psychotherapy are in the midst of a turbulent time. The increasing
      control of cost-cutting health maintenance organizations over health care
      delivery has resulted in a monumental shift in the field. Primary care providers
      prefer to treat psychiatric disorders with medication instead of psychotherapy.
      Consequently, psychiatrists and related mental health professionals must find new
      ways to offer treatment. The author suggests that this transition period offers a
      tremendous opportunity for psychiatrists and other therapists to look beyond the
      standard doctor-patient context and reach into the patient's community, involving
      other social organizations to form a network of total care. To understand how the
      mental health field reached this stage and to understand what lies ahead, it is
      essential to look to the past.

PMID- 9524378
TI  - A long-term psychotherapy group for children with chronic medical illness.
AB  - Group psychotherapy for children with chronic medical illness can be a powerful
      tool in facilitating their social and emotional adjustment to their condition. In
      this article, the author addresses the theoretical issues in developing and
      managing such a group, drawing on his experience with a long-term psychotherapy
      group of four children of varying ages and medical conditions. Themes arising
      from this group included universality of experience, understanding the
      disabilities of others, sharing, relationships with parents, and grief and loss.
      In addition to addressing developmental tasks of individual group members, the
      author presents therapist-related issues (e.g., transference,
      countertransference, the cotherapy relationship, and the therapist-parent
      relationship). The author concludes that participation in an ongoing
      psychotherapy group can provide medically ill children with considerable
      opportunity for growth, understanding, meaning, and adaptation.

PMID- 9524379
TI  - What do adult attachment scales measure?
AB  - Research suggests that attachment patterns can be measured as early as 12 months
      of age and that in the absence of major environmental change, they persist into
      adulthood. Evolving from three traditions, a number of assessment tools have been
      developed to study adult attachment. They range from semiclinical interviews to
      brief questionnaires and explore different relationship domains, from
      retrospective accounts of childhood experience to current romantic relationships.
      After exploring the theoretical background of the study of adult attachment, the
      authors review the format and the psychometric properties of several measures.
      Studies that compare measures are described. The article concludes with a
      discussion of unresolved questions about adult attachment that emerge from
      various measurement perspectives.

PMID- 9524380
TI  - Injury and pain in performing musicians: A psychodynamic diagnosis.
AB  - In recent years, there has been increased attention to the physical complaints of
      musical performers. Lockwood (1989) reviewed ailments encountered by physicians
      who treat musicians and maintained that "complaints of purely psychic origin are
      very unusual" (p. 225). The author disagrees with Lockwood's position. This
      article explores the multiple meanings of pain and injury in musicians. Clinical
      material illustrates how dynamic unconscious phenomena influence the musical
      performer's somatic complaints.

PMID- 9524381
TI  - Prinzmetal's angina and emotions: A neglected psychosomatic entity.
AB  - Prinzmetal's angina, a form of angina precipitated by vasoconstriction or spasm,
      appears to be a somatic phenomenon, but there is evidence, from research and case
      reports, of a major psychological component. In this study, individuals with
      Prinzmetal's angina were interviewed to determine the nature of their
      interpersonal relationships and their intrapsychic state at the time of onset of
      their chest pain. In addition, short developmental histories were obtained. The
      authors found that onset of chest pain was related to experiencing intense
      affect, and multiple levels of interpersonal and intrapsychic conflict, with
      strong conscious and unconscious, emotional and ideational links to previous
      traumas.

PMID- 9524382
TI  - The Krever Commission and public health.

PMID- 9524383
TI  - World trade and investment agreements: implications for public health.

PMID- 9524384
TI  - Tobacco access to youth: beliefs and attitudes of retailers.
AB  - Results of a telephone survey provide insights into the knowledge, attitudes and
      beliefs of tobacco merchants from two local health units. More than 90% of the
      retailers said they should not be able to sell cigarettes to minors. They are
      aware of laws prohibiting such sales but are sceptical about the impact on young
      people. The majority report being motivated to help protect the health of youth,
      however, they advise that legislation provides the main reason for not selling
      cigarettes to minors. Other responses and behaviours of the merchants help
      provide a profile of an important group that is being asked to stop selling
      tobacco to young people. The authors classify the retailers into three groups
      according to the potential influence on their behaviour of messages about health
      and threats of enforcement. One of the health units had implemented a local
      intervention, therefore we also compare responses between the two health units.
      This type of information can be used when selecting strategies to strengthen
      health policies. Such policies and strategies should include input and feedback
      from retailers of tobacco.

PMID- 9524385
TI  - [Cigarette usage in Quebec from 1985 to 1994: a comparison with Canada].
AB  - Smoking is responsible for the highest number of avoidable illnesses and deaths
      in Canada. Cigarette smoking declined considerably in the adult population
      between 1965 and 1986, but what has happened over the past decade? Quebec and
      Canadian public surveys were used to compare types of cigarette use in Quebec and
      Canada between 1985 and 1994, as well as to compare them by sex. In recent years,
      the prevalence of smoking has increased among Quebec men only. Differences
      between Quebec and Canada can be seen in the evolution of the quit rate and the
      prevalence of smokers. There does not appear to be any indication that
      differences in cigarette smoking between Quebec and Canada are being eradicated.
      In Quebec, the evolution of this habit differs according to sex, which indicates
      that certain factors affect men and women differently. The public survey data
      make it possible to follow trends in the medium and long term, whereas it is
      difficult to accurately track the evolution of cigarette smoking from one year to
      the next, given the small size of the samples in each region and the slow
      evolution of behaviour.

PMID- 9524386
TI  - [Mortality attributable to tobacco smoking in Quebec].
AB  - In industrialized countries, tobacco smoking is the main cause of preventable
      morbidity and premature deaths. Although mortality attributable to smoking has
      already been estimated for the population of the province of Quebec, it has never
      been studied on a regional basis. We calculated the mortality attributable to
      smoking by socio-sanitary regions of the province of Quebec for 10 fatal diseases
      positively associated with smoking. The calculations were made for the years 1984
      through 1993 taking into account Canadian Census data (demographic variables),
      the Sante-Quebec survey (prevalence of smoking), the death registry of the
      "Bureau de la statistique du Quebec" (mortalitry data), and the American cohort
      of the "Cancer Prevention Study II" (relative risks). For the diseases
      investigated, 24,637 and 62,711 deaths were attributable to smoking for women and
      men respectively during the period studied, thus representing 29.4% and 51.2% of
      attributable percentages. There is no statistical difference between the regions,
      which indicates a general problem for all the province. These data again confirm
      the incredible impact of smoking on public health. The struggle against smoking
      should be a primary area for action for the benefit of all Quebecers.

PMID- 9524387
TI  - Changes in ETS following anti-smoking legislation.

PMID- 9524389
TI  - Staging of adult smokers according to the transtheoretical model of behavioural
      change: analysis of an eastern Ontario cohort.
AB  - OBJECTIVES: 1) To describe the distribution of adult smokers in an existing
      cohort according to stages of change theory; and 2) to compare movements of these
      smokers through the stages of change. DESIGN: Secondary analysis of existing
      cohort data. SETTING: Eastern Ontario. PARTICIPANTS: Adult smokers who: 1)
      enrolled in a Quit & Win Challenge, or 2) received smoking cessation information
      (Quit Kit) from their area health unit, or 3) were randomly selected by telephone
      survey. RESULTS: 706 smokers were recruited and followed for one year. Only 2% of
      the adult smokers selected by random telephone survey were in the "action" stage
      at baseline, compared with 14% of the Quit and Win Challenge participants, and
      14% of the Quit Kit recipients. Variations in movement through the stages of
      change were observed between groups upon follow-up. CONCLUSIONS: The results
      suggest a need to use stage-matched approaches when developing population-based
      smoking cessation interventions.

PMID- 9524388
TI  - Public opinion regarding smoking in public places and workplaces in the greater
      Kingston area.

PMID- 9524390
TI  - Couple violence and psychological distress.
AB  - Except for anecdotal data, empirical research on the psychological well-being of
      abused men is scarce. This paper compares the mental health of non-victims with
      victims of physical and psychological violence among 562 Calgary couples.
      Physical and psychological violence were assessed by two subscales of the
      Conflict Tactics Scales and psychological distress was assessed by abbreviated
      anxiety and depression subscales of the SCI-90, a frequency of symptom measure.
      Female and male victims of either psychological-only or physical violence
      reported significantly higher rates of distress than nonvictims. Females
      exhibited higher depression and anxiety scores than their male counterparts,
      regardless of whether they were victims or non-victims of either type of
      violence. Being both a perpetrator and victim of either type of violence is
      associated with significantly higher levels of psychological distress for both
      genders. The theoretical and practical implications of these findings are
      discussed.

PMID- 9524391
TI  - Management of family and workplace stress experienced by women of colour from
      various cultural backgrounds.
AB  - Minority women identify finances and maintaining cultural values as their most
      commonly experienced stressors at home and in the work-place. A before and after
      study of ethnic minority women in focus group sessions led by a trained ethnic
      minority facilitator examined how social and workplace supports, or lack thereof,
      impact on the individuals' ability to manage daily life. Creative, effective
      solutions to stressors were identified by the participants. Outcomes were
      evaluated in terms of the impact of changes on the participants' coping styles in
      family and work life. Results indicate that a large percentage of women in this
      study felt discriminated against based on their culture/race, however, this
      perceived discrimination decreased after the focus groups. The predominant stress
      management techniques were prayer and music. Family support was the most
      influential factor in decreasing stress. The family is a major source of support
      for the working women, acting as a buffer to workplace pressures.

PMID- 9524392
TI  - A descriptive epidemiology of sport and recreation injuries in a population-based
      sample: results from the Alberta Sport and Recreation Injury Survey (ASRIS).
AB  - The 1996 Alberta Sport and Recreation Injury Survey is a retrospective study
      describing the annual incidence of injuries in the province of Alberta resulting
      from sport and recreational involvement. Data was collected by means of a
      telephone survey using random digit dialing techniques to obtain a representative
      sample of Albertans in the winter of 1995-96. The sample produced a total of
      3,790 respondents from 1,478 households evenly split between genders, with an age
      range of 6 to 93 years. The survey asked information regarding medically
      attended, non-fatal injuries resulting from sport and recreational activities.
      Findings reveal an annual incidence of sport or recreational injuries of 11%.
      Among those reporting a sport or recreational injury, the most common types of
      injuries were a sprained/torn ligament (31%), strained/pulled muscle (19%), and
      fracture (13%). The most common bodily locations of injuries were the knees (21%)
      and the ankle (14%).

PMID- 9524393
TI  - The effect of a community-based police surveillance program on snowmobile
      injuries and deaths.
AB  - Serious snowmobile injuries are preventable and associated with late-night
      travel, alcohol use, and speed. We studied the effectiveness of a community-based
      policing (STOP) program in the prevention of serious injuries related to
      snowmobile trauma in Sudbury, Ontario. Volunteers were trained in police protocol
      and were appointed special constables to increase policing on snowmobile trails
      from 1993-95. Snowmobile admissions and deaths in Sudbury were examined; the pre-
      (1990-1992) and post- (1993-1995) STOP seasons were compared. In the pre-STOP
      period, 102 injuries, 87 admissions, and 15 deaths occurred compared to 57
      injuries (p = 0.0004), 53 admissions (p = 0.00001) and 4 deaths (p = 0.13) in the
      post-STOP period. All other event and demographic features of the crashes
      remained similar. Significant economic savings were realized from this
      intervention; acute care costs savings exceeded $70,000/year and costs from death
      decreased by $5 million. An intervention involving enforcement on snowmobile
      trails can reduce the incidence of injuries from snowmobile-related trauma.

PMID- 9524394
TI  - [Factors associated with follow-up visit non-compliance after induced abortion].
AB  - Non-compliance to follow-up after an induced abortion is associated with poor
      compliance to contraception. This study was undertaken to determine which factors
      are associated with follow-up visit compliance after an induced abortion among
      1,661 women who had the operation at the Clinique de Planification des Naissances
      du Centre Hospitalier de I'Universite Laval. Factors associated with non
      compliance to follow-up include young age, smoking, previous induced abortion, a
      single sexual partner during the previous year, the use of oral contraceptives
      and advanced gestational age at the time of the procedure. Careful screening of
      these women might improve compliance with follow-up visits and contraception,
      which could in turn help to prevent repeat abortions.

PMID- 9524395
TI  - Improved disease reporting: a randomized trial of physicians.
AB  - OBJECTIVES: To determine if a heightened, passive surveillance system increases
      the number of physicians reporting two notifiable diseases during a six-month
      period. METHODS: We conducted a randomized trail among 145 community-based
      primary care physicians in two counties in Eastern Ontario. Intervention group
      physicians received a three-part intervention aimed at improving their
      communication with the health unit to whom all physicians are mandated to report
      notifiable diseases. The control group physicians remained part of the usual
      disease reporting system. The outcome was assessed by a relative risk comparing
      the number of physicians reporting among the intervention group to that in the
      control group. RESULTS: Seventy physicians received the intervention and 75
      physicians were in the control group. The relative risk for the number of
      physicians reporting at least one case was 5.9 (95% CI 2.6-13.2). CONCLUSIONS:
      The intervention had an impact on reporting of notifiable diseases by physicians.

PMID- 9524396
TI  - Hepatitis B associated with autohaemotherapy.

PMID- 9524397
TI  - WHO concludes that measles viruses are not associated with Crohn's disease.

PMID- 9524398
TI  - AIDS and HIV infection in the United Kingdom: monthly report.

PMID- 9524399
TI  - Measles in Victoria 1992 to 1996: the importance of laboratory confirmation.
AB  - Australia had a major measles epidemic in 1993 and 1994, which appeared to by
      pass Victoria. Victorian notification and laboratory testing data for measles,
      and public hospital discharge codes, from 1992 to 1996, were reviewed. The rate
      of measles notification in Victoria fell between 1992 and 1996. By contrast the
      national notification rate increased markedly in 1993 and 1994. The proportion of
      measles tests performed at the Victorian Infectious Diseases Reference Laboratory
      (VIDRL) which were positive increased for all age groups in 1993 and 1994. This
      increase was highest for the 15 to 19 years age group. The hospital discharge
      codes demonstrated an increase in the number of admissions for measles in 1993
      and 1994, largely for adolescents and younger adults. These data suggest Victoria
      had an age group specific measles outbreak, the magnitude of which was not
      reflected by the passive notification system. Reasons why younger age groups in
      Victoria appeared to avoid the epidemic are unclear.

PMID- 9524400
TI  - Communicable diseases surveillance.

PMID- 9524401
TI  - Occupational medicine in Canada and Poland in the 1990s.
AB  - Canada and Poland share many demographic and economic characteristics: both
      countries are relatively large, urbanised, historically dependent on extractive
      industries, and comparable in population. The principal differences reflect their
      recent histories and economic systems. We compare the development of occupational
      medicine in each country and the historical forces that shaped the specialty in
      each country. We describe certain features of the Canadian occupational health
      system that may be of interest and propose a program of scientific cooperation
      for mutual benefit.

PMID- 9524402
TI  - Mercury compounds and the immune system: a review.
AB  - This article reviews the literature data concerning the immunologic monitoring of
      animals and cell cultures exposed to mercury compounds. Mercury is present in
      nature as metallic mercury, mono- and bivalent inorganic compounds, and organic
      alkyl, aryl and alloxy-alkyl compounds. Methylmercury is most important in terms
      of environmental exposure while metallic mercury is the most common form to which
      workers are exposed. The database on immune function disturbances in human
      induced by mercury compounds is limited. Immunotoxicity assessment in animals,
      mainly in rodents, with subsequent extrapolation to man, is the basis of human
      risk assessment. The strength of in vitro immunotoxicity testing lies in studies
      aimed at unravelling mechanisms of immunotoxicity. These experimental
      investigations show clearly that mercury compounds can have immunomodulating
      activity. Mercuric chloride and methylmercury inhibit most of animal and human
      lymphocyte functions including proliferation, expression of cell activation
      markers on cell surface and cytokine production. These cells exhibit a greater
      sensitivity to the immunotoxic effects of methylmercury than to mercuric
      chloride. Repeated administration of mercuric chloride to rats, mice and rabbits
      can induce autoimmune response and a membranous nephropathy. In contrast, Lewis
      rats injected with mercuric chloride do not develop autoimmunity but exhibit
      immunosuppression. The immunosuppressive effects associated with exposure to
      chemical substances are often accompanied by increased susceptibility to
      challenge with infectious agents or tumour cells. Only few reports are available
      on animal studies of increased mortality connected with exposure to mercury
      compounds and challenge with infectious agents. It is difficult to establish a
      relationship between the observed immunomodulatory properties of mercury
      compounds and their possible carcinogenicity. In fact, the epidemiological
      studies performed so far failed to bring any conclusive evidence of
      carcinogenicity of mercury in animal experiments. The induction of renal tumours
      in male rodents by methylmercury was observed only.

PMID- 9524404
TI  - Comparison of the mutagenicity of chemical agents released during coke
      production.
AB  - Benzene- and acetone-extracted samples of airborne particulate matter collected
      in two coke plants were analysed for their content of genotoxic agents (coal tar
      pitch volatiles (CTPVs), polycyclic aromatic hydrocarbons (PAHs): benzo/a/pyrene,
      pyrene, dibenzo/a,h/anthracene, anthracene and fluoranthene) following the
      identification and quantification of the compounds as well as the evaluation of
      their mutagenic activity using in vitro reverse mutation assay. Results of
      determinations at the top section of coke batteries were compared. Mean
      concentrations of total dust, CTPVs and B/a/P were as follows: 2.06 mg/m3, 0.63
      micrograms/m3 in plant A, and 2.77 mg/m3, 0.89 mg/m3 and 0.35 micrograms/m3 in
      plant B, respectively. All the extracts of particulate matter samples increased
      the induction of bacterial mutation in both +S9 and -S9 tests. The exposures to
      mutagenic airborne particulate matter were in the range of 98-683 rev./m3 (-S9):
      714-2214 rev./m3 (+S9) in plant A, and 21-496 rev./m3 (-S9); 68-850 rev./m3 (+S9)
      in plant B. The correlation between mutagenic potential and concentrations of
      tested agents was insignificant. The coke oven emission seemed to be higher in
      plant A with side charging of coal.

PMID- 9524403
TI  - Determination of tissue polypeptide antigens (TPA) and carcinoembryonic antigen
      (CEA) in serum: its value in the preliminary cancer risk assessment in asbestos
      exposed workers.
AB  - Seeking the changes at the cellular level or at the level of cellular metabolism
      products, present in the biological fluids, in order to detect early stages of
      the carcinogenic process is an essential step in preventing cancer development
      among asbestos exposed workers. Carcinogenic biomarkers such as tissue
      polypeptide antigens (TPA) and carcinoembryonic antigen (CEA) were found very
      useful in this attempt. The objective of this work was to identify individuals at
      critical cancer risk in the population of workers exposed to asbestos and to
      evaluate the value of TPA and CEA determinations for this particular purpose. The
      study was carried out in the group of workers exposed to asbestos (n = 274). Age,
      exposure duration, smoking habits and the kind of job performed, were considered
      in the analysis of the results. To sum up, it should be concluded that in 22
      persons exposed to asbestos TPA values exceeded the cut off concentrations,
      established on the basis of the studies performed in the control group, and CEA
      value accounted for 10 ng/lm. Statistically significant differences in the
      percentage of TPA increased values between two groups under study were indicated.
      Such a relationship did not apply to CEA. In the exposed group, an evident effect
      of the age and exposure duration on the number of persons with TPA concentrations
      above the cut off, was also revealed. These changes show a growing tendency and
      statistical significance for TPA only. Smoking had a great impact on the
      occurrence of TPA increased concentrations. Three kinds of jobs were considered:
      operation of the production line, white collar workers and miscellaneous'. The
      significant differences in TPA concentrations between the operators and
      miscellaneous, and between white collar workers and miscellaneous were found.
      Therefore, it may be concluded that a similar percentage of TPA increased values
      was observed in the group of operators and white collar workers. The study
      allowed to identify, among those exposed to asbestos, 22 persons who should be
      covered with target medical care. It also indicated that TPA determination was
      more useful than that of CEA in this kind of investigations.

PMID- 9524405
TI  - Concentration of metals, ceruloplasmin, metallothionein and activity of N-acetyl
      beta-D-glucosaminidase and gamma-glutamyltransferase in pregnant women who smoke
      and in those environmentally exposed to tobacco and in their infants. II.
      Influence of environmental exposure in the Copper Basin.
AB  - Concentration of metals (Zn, Cu, Cd), Metallothionein (MT) and the activity of n
      acetyl?beta-glucosaminidase (NAG) in amniotic fluids and milk from smoking
      mothers and passive smokers, living in the area of higher environmental pollution
      with heavy metals, were measured. In active smokers a three-fold increase in Cd
      concentration, higher Cu and lower Zn concentrations, higher MT level and
      enhanced NAG activity in amniotic fluids as well as higher Cd, Cu and Zn
      concentrations and increased MT and NAG in milk were indicated, when compared to
      passive smokers. Some dynamics in metal and metallothionein secretion with
      mother's milk was noted on successive days after delivery. The highest MT level
      was observed during first 24 hrs postpartum, whereas Cd concentration was found
      to be highest on the third day. There were no significant differences in
      concentrations of Cu and Zn secreted with milk on those days. In environmentally
      exposed women higher Cd and Cu concentrations, enhanced MT level and Nag
      activity, higher amniotic fluid and lower milk Zn concentration were observed in
      comparison to women living in the Cieplice region.

PMID- 9524406
TI  - Occupational classification according to work demands: an evaluation study.
AB  - The use of job title as crude exposure measure in epidemiological studies is
      often inevitable when the available exposure data is scarce. In this study, an
      existing classification scheme of all job titles in the Netherlands into six
      categories of physical and mental work demands, constructed by expert judgement,
      was evaluated. Furthermore, a revision of this classification scheme for a
      research project on the relation between age, physical work demands, and
      musculoskeletal complaints was proposed and evaluated as well. For the
      evaluation, self-reported work demands, derived from questionnaire data of 38,921
      employees and quantified by a scale of physical work demands and mental work
      demands, were used. Based on comparison of the mean scale scores of the several
      categories of work demands at group level, both classification schemes showed
      construct validity. Notwithstanding several limitations, the use of the presented
      classification schemes in epidemiological studies seems particularly challenging
      and rewarding when analysing data at group level from large and heterogeneous
      occupational populations. These kind of exploratory studies may generate new
      hypothesis on the basic patterns concerning work-related disorders, and can also
      be informative from a policy making perspective.

PMID- 9524407
TI  - Occupational allergy to latex--life threatening reactions in health care workers.
      Report of three cases.
AB  - During the last decade natural rubber latex (NRL) allergy has been acknowledged
      as a major problem among rubber glove-wearing medical personnel. Epidemiological
      studies carried out in the European Union member states as well as in the United
      States reveal that 2% to 15% of health care workers are allergic to latex. Latex
      allergy symptoms range from mild contact urticaria to severe systemic reactions.
      Serious, generalised reactions occur in 6-8% of patients allergic to latex. The
      risk factors for latex-induced anaphylaxis have not as yet been identified. NRL
      allergy symptoms may occur in the workplace as well as outside the occupational
      environment. The authors present clinical cases of 2 nurses and 1 laboratory
      worker, who developed severe allergic reactions to latex: case 1--during
      prophylactic gynaecologic examination, case 2--in the course of inhalative
      bronchial challenge test with latex aqueous extract and case 3--while blowing up
      balloon at home.

PMID- 9524408
TI  - Respiratory irritative effects of trimethylbenzenes: an experimental animal
      study.
AB  - Sensory respiratory irritation effects of trimethylbenzene isomers (TMBs)
      (hemimellitene, mesitylene and pseudocumene) in male Balb/C mice were
      investigated in conditions of acute exposure and in male Wistar rats in
      conditions of repeated 90-day inhalation exposure to pseudocumene. The
      pseudocumene, mesitylene and hemimellitene concentrations depressing the
      respiratory rate to 50% (RD50) were 578, 519, 541 ppm, respectively. Inhalation
      exposure to pseudocumene for 90 days increased the total number of cell
      macrophages, polymorphonuclear leukocytes and lymphocytes number at all three
      test concentrations compared with the controls. Total protein lactate
      dehydrogenase (LDH) and acid phosphatase activity in bronchoalveolar lavage (BAL)
      were significantly increased in all exposed groups. Based on the effects observed
      in the respiratory tract, the threshold limit value of at least 10 ppm should be
      considered for the occupational exposure to trimethylbenzene isomers.

PMID- 9524409
TI  - Occupational medicine in Polish journals of 1996. Part 1.

PMID- 9524410
TI  - Occupational medicine in eastern journals of 1996. Part 1.

PMID- 9524411
TI  - Hoarseness--current concepts on etiologies and treatment alternatives.
AB  - The care of the human voice has challenged medical practitioners for centuries.
      Over the last 25 years we have seen significant advancements in the diagnosis and
      treatment of vocal disorders. This article is an overview of the more common
      voice disorders encountered in clinical practice and the diagnostic and
      management alternatives currently available. A thorough understanding of these
      conditions can lead to a prompt diagnosis and improved clinical outcomes in all
      patients, especially professional voice users. The insights presented are
      compiled through the eyes of a clinician and the heart of a performer.

PMID- 9524412
TI  - Treatment of persistent Pfiesteria-human illness syndrome.
AB  - Patients with exposure to Pfiesteria toxin have developed an illness, Pfiesteria
      human illness syndrome, characterized by skin lesions, headache, myalgias,
      conjunctival irritation, bronchospasm, abdominal pain, secretory diarrhea, recent
      memory loss, and difficulties with number sequencing. Not all patients
      demonstrated all features of the syndrome. The natural history of Pfiesteria
      human illness syndrome shows that most patients' symptoms improve without
      treatment. This article reports the improvement of symptoms that had persisted
      for over one month in five patients, which the author attributes to treatment
      with cholestyramine. These patients were self-referred to the Pocomoke River Rash
      and Associated Illness Center, a clinic that opened on August 6, 1997, in
      response to the need for a central facility for diagnosis of human illness
      acquired from Pfiesteria. Until the Pfiesteria toxin(s) is isolated and
      characterized, and laboratory diagnostic tests are available, physicians must be
      able to recognize Pfiesteria-human illness syndrome and intervene when symptoms,
      particularly memory loss and diarrhea, cause significant impairment in daily
      activities. There are no precedents for the treatment of Pfiesteria or any
      dinoflagellate toxin-related human illness reported in the literature. The
      successful use of cholestyramine reported here may provide a model for
      understanding dinoflagellate toxin physiology in the human body. This paper
      reports an uncontrolled observational study. When identification of the toxin is
      completed, a basis for properly controlled studies will be available.

PMID- 9524413
TI  - Treatment of congestive heart failure with beta-adrenergic blockers: a brief
      review of literature.
AB  - The importance of the adrenergic nervous system in support of hemodynamics in
      patients with congestive heart failure has been known for a long time. Thus, when
      beneficial effects of beta-blocker therapy in patients with resistant congestive
      heart failure were reported more than two decades ago, such an approach was
      deemed counterintuitive. Despite the skepticism, numerous reports, including well
      planned, randomized studies, confirmed the beneficial effects of various beta
      blockers on congestive heart failure. Recently, a new generation of beta-blocker,
      carvedilol (Coreg), which combines nonselective beta-blocking and vasodilating
      properties, was cleared by the U.S. Food and Drug Administration for the
      treatment of congestive heart failure. This article is a brief historical review
      of the literature regarding the use of beta-blockers for the treatment of
      congestive heart failure.

PMID- 9524414
TI  - Dietary controls produce positive results for a non-insulin-dependent diabetes
      mellitus patient.
AB  - Renal disease is a leading cause of death and disability for diabetic patients.
      Diabetic nephropathy is responsible for half of the cases of end-stage renal
      disease in the United States. For non-insulin-dependent diabetes mellitus
      patients, the prevalence of diabetic nephropathy varies from 15% to 60% and is
      influenced by genetic background. Early screening and controlling of microalbumin
      levels are essential to affect the outcome of diabetic nephropathy. Studies show
      that clinical renal dysfunction in diabetics does not correlate well with the
      histological abnormalities. Strategies for nephropreservation include close
      lipid, glycemic, and blood pressure control, and tobacco termination. Use of
      angiotensin-converting enzyme inhibitors exert nephroprotective effects beyond
      their beneficial blood pressure-lowering effects. The importance of strict diet
      is emphasized in a case presentation.

PMID- 9524415
TI  - Advance directives in internal medicine outpatient residents' clinics.
AB  - This study assessed the frequency of obtaining advance directives from patients
      of internal medicine residents in two Baltimore teaching programs. A survey was
      conducted of the medical records of 130 patients in the medical clinics from
      these programs. Independent variables included age, sex, and race. Dependent
      variables included documentation of terminal illnesses, resuscitation or code
      status, and discussion regarding resuscitation status. Only 25 of 130 patients
      (19%) had a resuscitation status recorded, 24 were documented as full
      resuscitation and 1 as do not resuscitate. Of subjects older than 65 years, 23%
      had a resuscitation status. Although 4 of 37 subjects older than 65 years had a
      terminal illness, none had advance directives.

PMID- 9524416
TI  - Early patriot physicians of Maryland and the First Provisional Convention, June
      22, 1774.

PMID- 9524417
TI  - Adult vaccination: not just for kids anymore.

PMID- 9524418
TI  - User beware. How to spot potential security risks on the Internet.

PMID- 9524419
TI  - Medical symbols. One snake or two?

PMID- 9524420
TI  - Medicine faces battle for reform in legal environment.

PMID- 9524421
TI  - Infant mortality statistics from the linked birth/infant death data set--1995
      period data.
AB  - OBJECTIVES: This report presents infant mortality statistics from the linked
      birth/infant death data set (linked file)-1995 period data by a variety of
      maternal and infant characteristics. Trends in birthweight-specific infant
      mortality rates from 1985-95 are also discussed. METHODS: Descriptive tabulations
      of data from the linked file are presented. The data include infant deaths in
      1995, which are linked to their corresponding birth certificates, whether the
      birth occurred in 1995 or 1994. The denominator used to compute infant mortality
      rates is the National Center for Health Statistics (NCHS) natality file, which
      includes all births in 1995. Data are weighted to compensate for the 2.5 percent
      of infant death records that could not be linked to their corresponding birth
      certificates. RESULTS: In general, mortality rates were lowest for infants born
      to Asian and Pacific Islander mothers, followed by white, American Indian, and
      black mothers. Rates for infants of Hispanic origin mothers were slightly lower
      than or comparable to those for infants of white mothers, except for infants of
      Puerto Rican mothers who had higher infant mortality rates. Infant mortality
      rates were higher for those infants whose mothers began prenatal care after the
      first trimester of pregnancy, were teenagers or 40 years of age or older, did not
      complete high school, were unmarried, or smoked during pregnancy. Infant
      mortality was also higher for male infants, multiple births, and infants born
      preterm or at low birthweight. In 1995, 63 percent of all infant deaths occurred
      to the 7.3 percent of infants born at low birthweight. From 1985-95, birthweight
      specific infant mortality rates declined most rapidly for infants weighing 750
      1,499 grams at birth. The leading causes of infant death varied considerably by
      race and Hispanic origin. For infants of black mothers, Disorders related to
      short gestation and unspecified low birthweight was the leading cause of infant
      death, with an infant mortality rate 4.5 times higher than that for infants of
      white mothers. For infants of American Indian mothers, rates for Sudden infant
      death syndrome were 2.9 times and for Accidents and adverse effects 3.6 times
      higher than those for infants of white mothers. For infants of Hispanic mothers,
      mortality rates from Sudden infant death syndrome were one-third lower than those
      for infants of white mothers.

PMID- 9524422
TI  - [Extracorporeal membrane oxygenation in neonatology: review of the use of the
      method].
AB  - Extracorporeal life support and extracorporeal membrane oxygenation characterize
      the use of mechanical devices for temporary support of heart and lung function.
      The mechanical circuit consists of a blood pump (heart), membrane oxygenator
      (lung: which accomplishes both carbon dioxide removal and oxygen delivery), heat
      exchanger and a servo-control module. Venous blood is drained from the right
      atrium through the right internal jugular vein, and returned oxygenated through
      either the right common carotid artery (venoarterial bypass), or into a large
      vein (venovenous bypass). All patients treated must be free of coagulopathies, as
      all patients are anticoagulated. Neonatal candidates should be older than 34
      weeks gestational age and weigh more than 2000 grams. As of March, 1997 twenty
      six patients have been treated with extracorporeal life support at Tulane Medical
      Center with an overall survival rate of 62%. Twelve neonates with either meconium
      aspiration or pneumonia have been treated with a 100% survival. Six children with
      congenital diaphragmatic hernia have been unsuccessfully treated.

PMID- 9524423
TI  - [Invasive fungal infection in malignant hematologic diseases].
AB  - In patients with hematological malignancies invasive mycoses occur frequently. In
      this retrospective study autopsy and histopathology material of 171 patients with
      hematological malignancy who had died between 1994 and 1996 at the 1st Department
      of Internal Medicine (Hematology), St. Laszlo Hospital, Budapest was analysed. In
      cases with invasive fungal infection post mortem results were compared to
      clinical and microbiological data. Through the three years' period an invasive
      mycosis could be confirmed in 33 patients by autopsy. Aspergillosis occurred in
      21, candidiasis in 11, other fungal infections in 2 cases, a double infection was
      seen in 1 patient. The incidence was 19.2% (in invasive candidiasis: 6.4%, in
      aspergillosis 12.2%). Invasive aspergillosis most frequently was seen in the lung
      (71%), while candidiasis occurred mainly in the intestinal tract (42%). Cultures
      for mycology were collected from the autopsy material of 9 patients, of which 8
      gave positive results. A previous fungal colonisation results was confirmed in 23
      patients, but based on colonisation conclusions rarely could be driven concerning
      the species causing invasive infection. Sensitivity of Aspergillus antigen and
      antibody tests was 45 and 50%, respectively. Predisposing factors for invasive
      aspergillosis and candidiasis were similar, except for duration of neutropenia
      (24 vs. 12 days, p < 0.004). The antifungal drug most frequently used was
      amphotericin B. We observed a persisting infection in invasive pulmonary
      aspergillosis and chronic disseminated candidiasis in spite of the administration
      of a cumulative dosis of 1-2 g. Most frequently Aspergillus infections--primarily
      that of the lung--can be seen. Presence of invasive mycoses can usually be
      confirmed in vivo, but an early diagnosis still remains unsolved.

PMID- 9524424
TI  - [Systemic lupus erythematosus and pregnancy (effect of pre-conception hematologic
      disorders on fetal outcome)].
AB  - The aim of the study was to determine the fetal and neonatal outcomes of
      pregnancies conceived during the inactive phase of systemic lupus erythematosus
      (SLE). Fetal and neonatal outcomes in 75 pregnancies of 33 patients with SLE were
      analyzed. In 19 patients (57.6%) the SLE also had hematological autoimmune
      presentations prior to gestation, such as anemia, thrombopenia, garnulocytopenia,
      and antiphospholipid antibody and/or lupus anticoagulant (APA). Out of 75
      pregnancies, 19 elective terminations were carried out because the disease was
      active or for non-medical reasons. The adverse fetal outcomes of those 56
      pregnancies which occurred during the inactive phase were compared with those of
      the control patients. In SLE, the rates of spontaneous abortions (46.4%) and
      newborns with low (< 2500 gr) birthweight (36.7%) were found to increase roughly
      three times that of the controls and the perinatal fetal loss (16.7%) also
      increased significantly as compared with the control group (28.5 per thousand).
      APA noted at any time before pregnancy increased the low birthweight rate (75%)
      six fold and the perinatal loss (33.3%) more than ten fold but did not affect the
      rate of spontaneous abortions. Any kind of hemocytopenias without APA, noted
      before pregnancy did not worsen the fetal outcome in SLE. Neonatal lupus was
      diagnosed in 2 out of the 30 newborns. Our results suggest that among the
      hematologic manifestations of SLE presenting before pregnancy, APA can predict
      the high risks of low birthweight and perinatal fetal loss as opposed to
      hemocytopenias.

PMID- 9524425
TI  - [The place of enalapril in the management of hypertension].
AB  - In Hungary the use of angiotensin converting enzyme inhibitor enalapril has
      emerged as one of the most important drugs in the treatment of hypertension. The
      aim of our study was to evaluate the antihypertensive effect of enalapril of
      Hungarian production in combination therapy and alone, according to sexes, to the
      body mass index, among smokers and non smokers as well as non diabetic and in
      patients with diabetes (IDDM and NIDDM). The diurnal blood pressure values were
      registered by a 24 hour ambulatory blood pressure monitor. During the 6 weeks of
      the enalapril therapy (n = 28) both the daytime (141/84 vs. 135/80 mmHg) and the
      night-time (130/78 vs. 124/72 mmHg) blood pressure values decreased; the increase
      of diurnal indices during the therapy (SI/DI 6/8% vs. 8/10) reflect the 24 hour
      long lasting effect of the drug. The body mass index had no influence on the
      efficacy of treatment. Our results indicate that enalapril manufactured in
      Hungary is an effective antihypertensive drug both in monotherapy and in
      combination, in both sexes (especially in men), irrespective of the body weight,
      in non-smokers and especially in smokers, in insulin dependent and in non-insulin
      dependent diabetes mellitus alike.

PMID- 9524426
TI  - [Perianal ulceration as the leading symptom of childhood Langerhans-cell
      histiocytosis].
AB  - The authors present a case history for a two-year-old boy in whom the study of
      perianal ulcer helped to diagnose the Langerhans cell histiocytosis. The authors
      emphasize the diagnostic value of intertriginous ulcers in identifying the above
      mentioned disease.

PMID- 9524427
TI  - [Jozsef Kovcs, professor of surgery].

PMID- 9524428
TI  - [Mor Kaposi (1837-1902) prominent figure in medical history].

PMID- 9524429
TI  - [Memorial tablet dedicated to Jozsef Rozsay, geriatrist].

PMID- 9524430
TI  - Oral effects of smokeless tobacco use by professional baseball players.
AB  - This is a review of studies conducted from 1988-90 on the oral consequences of
      snuff and chewing tobacco use among professional baseball players. About half of
      the players studied were smokeless tobacco (ST) users, the majority of whom used
      snuff. Compared with non-users, players who used ST showed a significantly higher
      prevalence of leukoplakia, which was related to placement of the ST quid, and the
      frequency, amount, duration, and type of ST used. Sites adjacent to these mucosal
      lesions showed an increased prevalence of gingival recession with associated
      attachment loss, cervical abrasion, and root caries than did comparable sites in
      non-users. Extrinsic stain and occlusal attrition were also more frequent in ST
      users than in non-users. While ST use placed players at significantly increased
      risk for mucosal lesions and other oral problems, no differences were found
      between ST non-users and users in measurements of batting, fielding, and pitching
      performance during the baseball season.

PMID- 9524431
TI  - Epidemiology of cancer and other systemic effects associated with the use of
      smokeless tobacco.
AB  - Persons who use chewing tobacco and snuff experience an increased risk of oral
      cancer. Because of the pharmacologic properties of nicotine and other
      constituents of smokeless tobacco, there is also concern that smokeless tobacco
      products may lead to cardiovascular diseases as well. The relatively few human
      population studies to date conflict with respect to whether smokeless tobacco use
      elevates cardiovascular risk factors or leads to cardiovascular disease or death
      from cardiovascular causes. Hemoglobin adducts to carcinogens present in
      smokeless tobacco products are measurable in the blood of smokeless tobacco
      users, indicating that smokeless-tobacco-related carcinogens circulate throughout
      the body. This prompts a concern that smokeless tobacco may increase risks of
      other cancers as well. The evidence to date from epidemiologic studies indicates
      no relationship between smokeless tobacco and bladder cancer, but there is
      suggestive evidence linking smokeless tobacco use to prostate cancer risk. Only
      single studies have been conducted of some cancers, and inconsistencies among
      studies of the same cancer site have been reported. Molecular epidemiologic
      studies may help identify markers of malignant transformation in smokeless
      tobacco users that may help in early intervention to prevent or ameliorate the
      consequences of oral cancer. Further studies are needed to determine more clearly
      the cardiovascular and non-oral cancer risks potentially associated with
      smokeless tobacco use.

PMID- 9524432
TI  - Chemical composition and carcinogenicity of smokeless tobacco.
AB  - In the United States, smokeless tobacco (ST) is marketed as chewing tobacco and
      as oral snuff. During the past 15 years, consumption of chewing tobacco has
      declined by 30.6%, whereas snuff use has significantly increased, namely, by
      51.8%. This increase is primarily due to the growing popularity of oral snuff use
      among teenage and young adolescent males. Chewing of tobacco is associated with
      an increased risk for oral cancer. Snuff dipping is causally and specifically
      associated with cancer of the cheek, gum, and pharynx. In laboratory animals,
      snuff induces cancer of the mouth. Several carcinogens have been identified in
      ST, the tobacco-specific N-nitrosamine (TSNA), N'-nitrosonornicotine (NNN), and
      4(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) being the most important. NNN
      and NNK are formed from nicotine during curing, aging, and especially during
      fermentation of tobacco. Oral swabbing of a low concentration of a mixture of NNN
      plus NNK in water induces oral tumors in rats. The concentration of the strongly
      carcinogenic TSNA is higher in snuff than in other ST products. According to our
      analytical studies, the three leading snuff brands in the US (92% of the market)
      contain far higher concentrations of nicotine, unprotonated nicotine, and TSNA
      than the less popular brands. Thus, the leading US snuff brands are the strongest
      inducers of nicotine dependence and also have the highest carcinogenic potential.

PMID- 9524433
TI  - Smokeless tobacco: an addicting drug.
AB  - In 1986, the Surgeon General concluded that smokeless tobacco is an addictive
      drug sharing many qualities with other drugs of abuse such as morphine and
      cocaine. Smokeless tobacco can be used to deliver psycho-active and dependence
      producing levels of nicotine. Tolerance develops with repeated use, causing the
      user to increase nicotine dosing through increased use and/or switching to
      products with higher nicotine yields. Clinical signs of nicotine withdrawal
      develop upon cessation of use. Recent data show that smokeless tobacco products
      vary widely in their nicotine dosing capabilities. Low-dose products tend to be
      those commonly marketed toward, and used by, young people without previous
      smokeless tobacco experience. Many of these people develop dependence and switch
      to high-dose products. The present article discusses each of these qualities of
      smokeless tobacco in greater detail. The article also discusses qualities of
      smokeless tobacco that make it an effective nicotine delivery device that leads
      to addiction.

PMID- 9524434
TI  - Systemic absorption and effects of nicotine from smokeless tobacco.
AB  - Nicotine is absorbed in substantial quantities from smokeless tobacco and could
      contribute to the adverse consequences of smokeless tobacco use. Chronic systemic
      exposure to nicotine could contribute to accelerated coronary artery disease,
      acute cardiac ischemic events, and hypertension. Systemic absorption of sodium
      and mutagenic chemicals from smokeless tobacco could aggravate hypertension or
      cardiac failure, or contribute to cancer, respectively. Information concerning
      the potential hazards of nicotine and other systemically absorbed toxins may be
      incorporated into educational programs to discourage the use of smokeless
      tobacco.

PMID- 9524435
TI  - Prevention and treatment of smokeless tobacco use.
AB  - A review of the literature examining school-based prevention and treatment
      intervention programs for smokeless tobacco users is provided. Although few
      school-based prevention studies have been conducted, the results are promising.
      Many of the treatment studies that have been conducted, thus far, are limited due
      to the sample size and the lack of a control group. However, of the studies that
      have not had these limitations, the results are also promising. In general,
      studies show that intervention in the dental office can be effective and that
      group behavioral treatment may also improve cessation rates over minimal contact.
      On the other hand, pharmacological treatment, which has primarily focused on 2 mg
      nicotine gum, has not been found to be an effective treatment. Dentists are in an
      ideal position to advise and assist smokeless tobacco users to quit. The majority
      of smokeless tobacco users want advice and help from their dentists, and a
      significant number indicate that discussion of the negative oral effects from the
      use of smokeless tobacco has an impact on their desire to quit.

PMID- 9524436
TI  - A spit tobacco cessation intervention for college athletes: three-month results.
AB  - Sixteen colleges were matched on the baseline prevalence of spit tobacco (ST)
      use, and college pairs were randomized, one to the intervention and the other to
      the control group. Baseball and football athletes at each intervention college
      received: an oral examination by a dental professional who pointed out ST-related
      problems in the athlete's mouth and advised him to quit ST use; counseling by a
      dental hygienist on strategies to cope with cravings and triggers for use; and
      two follow-up telephone calls. At the three-month follow-up, quit rates were 24%
      and 16% for the intervention (n = 171) and control (n = 189) groups, respectively
      (p < 0.05). As the reported amount of ST used weekly increased, the percent of
      individuals who quit at 3 mos decreased (p < 0.05). Dental professionals appear
      to be effective in promoting spit tobacco cessation at 3 mos post-intervention in
      male college athletes, especially among those using lesser amounts of ST.

PMID- 9524437
TI  - Germ theory vs. community theory in understanding and controlling the
      proliferation of biofilms.
AB  - Germ theory and pure culture methods have provided invaluable information
      concerning the role of bacteria in diseases resulting from a single organism
      which bypasses a host's defenses. However, they do not provide sufficient
      information concerning the synergisms which allow the members of biofilm
      communities to proliferate more effectively as communities rather than as
      individuals. The mechanisms of these synergies are potential targets for
      antimicrobial agents as well as potential mechanisms of resistance to
      antimicrobial agents. Understanding community-level phenomena in oral biology
      requires the culture, identification, and classification of functional plaque
      communities as well as new methods of identifying and quantifying communal
      relationships. Cultured biofilm communities also provide ideal models of
      bacterial self-organization in which information related to adaptive strategies
      arises not only through the recombination of genes within genomes, but also
      through the recombination of organisms within communities.

PMID- 9524438
TI  - Growth dynamics in a natural biofilm and its impact on oral disease management.
AB  - Measurements of the microbial growth dynamics in natural biofilm communities are
      almost non-existent. In a recent study, the biofilm formation on teeth was
      examined. A previously unknown active period of bacterial division occurred at a
      certain density of plaque bacteria on tooth enamel. The density-dependent cell
      division phase of plaque formation contributed 90% of the biomass in the first 24
      hrs of plaque formation. This suggested that growth was induced by the bacteria.
      In vitro assays were developed for rapid evaluation of the growth of surface
      linked bacteria by the measurement of cellular components associated with growth
      on a per cell per time basis. Cell-free supernatants (termed START) of media in
      contact with bacteria were assayed for their effects on DNA synthesis and other
      cellular components associated with growth. START was found to increase the
      incorporation of [3H-methyl]-thymidine on a per cell per time basis, when
      compared with media not in contact with bacteria. Additional in vivo studies and
      in situ-based models of complex biofilms are needed if all of the mechanisms
      involved in the rapid accumulation of biofilm bacteria on teeth and other
      surfaces are to be understood.

PMID- 9524439
TI  - Physico-chemical interactions in initial microbial adhesion and relevance for
      biofilm formation.
AB  - This paper summarizes initial microbial adhesion events in dental plaque
      formation, including the physico-chemistry of the interaction between micro
      organisms and solid substrata, detachment phenomena under the fluctuating shear
      of the oral cavity, co-adhesion between pairs of microbial strains, and
      biosurfactant release. A hypothesis is forwarded on how these initial events
      might influence the final microbial composition and structure of the plaque,
      although it is simultaneously emphasized that the necessary techniques for
      verification of the hypothesis have only recently become available, and
      supporting evidence is still to be collected.

PMID- 9524440
TI  - In vitro models that support adhesion specificity in biofilms of oral bacteria.
AB  - Adhesion to adsorbed pellicles and interspecies co-adhesion to form plaque
      biofilms involve selective interactions of bacterial adhesins with specific
      receptors. Our laboratory has devised in vitro assays for co-adhesion between
      Actinomyces naeslundii and Streptococcus oralis or Porphyromonas gingivalis on
      saliva-coated mineral and hexadecane droplet substrata. P. gingivalis structures
      significant for co-adhesion with A. naeslundii include surface vesicles and
      fimbriae. A family of arginine-specific cysteine proteinases in vesicles may be
      involved in adherence to bacteria, to host cells, and to matrix proteins. New
      research from several laboratories has found that such proteinases are processed
      from genes encoding polyproteins containing both proteinase and hemagglutinin
      domains. In addition to enzyme-substrate recognition, bacterial adhesion is often
      determined by specific protein-peptide and lectincarbohydrate recognition. A.
      naeslundii--salivary prolinerich protein, S. gordonii--salivary alpha-amylase,
      and Treponema denticola--matrix protein recognition are examples of the former.
      Co-adhesion of A. naeslundii and S. oralis is an example of the latter. Lactose
      can selectively desorb A. naeslundii cells from mixed biofilms with S. oralis, a
      demonstration of the significance of specificity. Although non-specific forces
      are probably secondary to stereochemical fit in determining the selective range
      of surfaces that bacteria have evolved to recognize and bind, they probably help
      stabilize non-covalent bonds within aligned, complementary domains.

PMID- 9524441
TI  - Phagocyte-bacteria interactions.
AB  - Recognition and phagocytosis of micro-organisms in a serum-poor environment
      represent innate immunity against many extracellular pathogens. As a paradigm for
      such processes, we discuss the recognition of Klebsiella pneumoniae by alveolar
      macrophages and monocyte-derived macrophages in the absence of serum. Macrophages
      recognize and subsequently kill Klebsiella expressing Man-alpha 2/3-Man or Rha
      alpha 2/3-Rha sequences in their capsular polysaccharides by two mechanisms: (a)
      recognition of the capsular structures by macrophage mannose receptors, and (b)
      opsonization by the lung surfactant protein A (SP-A), which binds to the capsular
      polysaccharides of Klebsiella and to SP-A receptors on the macrophages. Sp-A may
      also enhance phagocytosis by increasing the activity of macrophage mannose
      receptors. We conclude that a specific microbial surface structure may be a
      target for recognition by macrophages via several mechanisms, as exemplified in
      the case of Klebsiella capsular polysaccharides. Multiple recognition mechanisms
      of pathogens by macrophages may be essential to provide innate immunity to reduce
      the frequency of infections caused by a relatively less virulent bacterium in the
      immuno-compromised host.

PMID- 9524442
TI  - Bacterial attachment to uro-epithelial cells: mechanisms and consequences.
AB  - Microbial attachment to mucosal surfaces is a first step in mucosal infection.
      Specific interactions between microbial surface ligands and host receptors
      influence the distribution of microbes in their sites of infection. Adhesion has
      often been regarded as a sufficient end point, explaining tissue tropism and
      bacterial persistence at mucosal sites. Adherence, however, is also a virulence
      factor through which microbes gain access to host tissues, upset the integrity of
      the mucosal barrier, and cause disease. The induction of mucosal inflammation is
      one aspect of this process. Bacterial attachment to mucosal surfaces activates
      the production of pro-inflammatory cytokines that cause both local and systemic
      inflammation. Epithelial cells are one source of these cytokines. The binding of
      fimbrial lectins to epithelial cell receptors triggers transmembrane signaling
      events that upregulate cytokine-specific mRNA and increase cytokine secretion. P
      fimbriae that bind the globoseries of glycolipids cause the release of ceramides
      and activation of the ceramide signaling pathway which contributes to the IL-6
      response. Spread of cytokines and other pro-inflammatory mediators from the local
      site contributes to the symptoms and signs of infection.

PMID- 9524443
TI  - Consequences of biofilm and sessile growth in the large intestine.
AB  - The human colonic ecosystem is an extremely complex environment comprised of
      several hundred different strains of bacteria. Studies were undertaken to
      determine whether these organisms formed metabolic or genotypically distinct
      assemblages in the gut microbiota in relation to polysaccharide fermentation.
      Measurements of depolymerizing enzymes (4 polysac-charidases, 6 glycosidases)
      showed that specific amylase and pectinase activities were comparable in bacteria
      desorbed from the surfaces of food particles and in non-particulate organisms.
      However, xylanase, beta-xylosidase, arabinogalac-tanase, alpha
      arabinofuranosidase, and beta-galacturonidase activities were always
      significantly greater in particulate bacteria. Short-term in vitro fermentations
      with both groups of bacteria showed marked differences in relative rates of
      starch, arabinogalactan, and mucin metabolism, while rates of fermentation
      product formation with pectin and xylan were broadly comparable. Significant
      differences were observed with respect to formation of individual fermentation
      products, especially when mucin or pectin were substrates, where particulate
      bacteria produced proportionally higher amounts of acetate. Bacteriological
      studies showed that communities of polymer-degrading bacteria and other groups of
      intestinal anaerobes growing on particulate matter were essentially similar to
      those occurring elsewhere in the gut lumen, at genus and species levels. In vitro
      colonization experiments demonstrated that a variety of polysaccharide-fermenting
      bifidobacteria and bacteroides--together with other cross-feeding organisms such
      as peptostreptococci, fusobacteria, and coliforms--rapidly attached to
      particulate intestinal materials.

PMID- 9524444
TI  - Host-pathogen interactions in bacterial endocarditis: streptococcal virulence in
      the host.
AB  - To identify streptococcal genes that are expressed during experimental
      endocarditis, we developed a promoter-less dual reporter gene-fusion (amy, cat)
      plasmid, pAK36. Chromosomal DNA from S. gordonii V288 was digested with Sau3A1.
      The resulting fragments were ligated into pAK36. Following transformation into S.
      gordonii, the library of random gene fusion clones was inoculated into a rabbit
      to induce experimental endocarditis. Chloramphenicol treatment effected positive
      selection. Upon euthanization of the rabbits, the valvular vegetations were
      excised in a sterile field. Surviving clones were isolated and screened in vitro
      for chloramphenicol sensitivity and negative amylase activity. From the 48
      randomly picked, double-negative clones, DNA was isolated and analyzed by
      Southern hybridization with labeled pAK36 probe. Different insertion patterns
      were identified, suggesting that no fewer than 13 S. gordonii genes were induced.
      Therefore, S. gordonii genes are induced during experimental endocarditis, which
      may contribute to virulence.

PMID- 9524445
TI  - Bacterial metabolism in dental biofilms.
AB  - Dental biofilms could have a structure which, in sections, looks like tissue. The
      internal structure of the dental biofilm could be the result of interbacterial
      adhesion mechanisms in combination with nutritional conditions characterized by
      multiple nutrient starvation. The preservation of the structure of the biofilm
      over time may also involve the ability of the bacteria to withstand environmental
      stresses such as starvation, reactive oxygen products, and acid. The present
      review will describe, first, the regulation of the metabolic defense against
      environmental stresses and then focus mainly on the energy metabolism of dental
      biofilms.

PMID- 9524446
TI  - Nutritional influences on biofilm development.
AB  - The amounts and types of nutrients in the environment influence the development
      and final bacterial and chemical composition of biofilms. In oligotrophic
      environments, organisms respond to nutrient stress by alterations in their cell
      morphology and cell surfaces, which enhance adherence. Little is known of the
      responses to stress by bacteria in the animal oral cavity. The environment in the
      oral cavity is less extreme, and saliva provides a constant source of nutrients.
      Catabolic cooperation among oral bacteria allow carbon and nitrogen from salivary
      glycoproteins to be utilized. Modification of growth environments of oral
      bacteria can influence their cell surfaces and adhesion. Studies in experimental
      animals have shown that feeding either glucose or sucrose diets or fasting has
      little effect on the initial stages of development of oral biofilms. However,
      diet can influence the proportions of different bacterial species later in
      biofilm development. Studies of competition among populations in communities of
      oral bacteria in vitro and in vivo have shown the significance of carbon
      limitation and excess and changes in environmental pH. Relatively few studies
      have been made of the role of a nitrogen metabolism in bacterial competition in
      biofilms. In keeping with biofilms in nature, oral biofilms provide a sequestered
      habitat, where organisms are protected from removal by saliva and where
      interactions among cells generate a biofilm environment, distinct from that of
      saliva. Oral biofilms are an essential component in the etiologies of caries and
      periodontal disease, and understanding the biology of oral biofilms has aided and
      will continue to aid in the prevention and treatment of these diseases.

PMID- 9524447
TI  - Analysis of gene expression in Streptococcus mutans in biofilms in vitro.
AB  - The purpose of this study was to develop methods for the consistent production of
      biofilms of S. mutans containing reporter gene fusions, and to examine the
      expression of genes involved in sucrose metabolism in adherent populations of
      this organism. Three strains of S. mutans harboring reporter gene fusions to the
      gene promoter regions of the gtfBC genes, ftf, and scrA were grown in a
      Rototorque biofilm fermenter in a tryptone-yeast extract-sucrose medium. Quasi
      steady-state levels of reporter gene activity were measured after the biofilms
      were grown for either 48 hrs of 7 days. Also, induction of gene expression by the
      addition of sucrose to biofilm cells was monitored. Reporter gene activity was
      measurable from all gene fusion strains. This study (i) establishes the
      feasibility of doing detailed molecular and physiologic studies on immobilized
      populations of S. mutans, (ii) demonstrates that the polysaccharide synthesis
      machinery of S. mutans is differentially expressed in biofilms, and (iii) opens
      the way for a more detailed analysis of the environmental signals and signal
      transduction pathways governing the regulation of gene expression by S. mutans
      cells that are immobilized on a solid surface.

PMID- 9524449
TI  - Mathematical modeling of biofilms.
AB  - A set of mathematical equations constitutes a mathematical model if it aims to
      represent a real system and is based on some theory of that system's operation.
      On this definition, mathematical models, some very simple, are everywhere in
      science. A complex system like a biofilm requires modeling by numerical methods
      and, because of inevitable uncertainties in its theoretical basis, may not be
      able to make precise predictions. Nevertheless, such models almost always give
      new insight into the mechanisms involved, and stimulate further investigation.
      The way in which diffusion coefficients are measured for use in a model,
      particularly whether they include effects of reversible reaction, is a key
      element in the modeling. Reasons are given for separating diffusion from
      reversible reaction effects and dealing with them in a separate subroutine of the
      model.

PMID- 9524448
TI  - Artificial dental plaque biofilm model systems.
AB  - Difficulties with in vivo studies of natural plaque and its complex,
      heterogeneous structure have led to development of laboratory biofilm plaque
      model systems. Technologies for their culture are outlined, and the rationale,
      strengths, and relative uses of two complementary approaches to microbial models
      with a focus on plaque biodiversity are analyzed. Construction of synthetic
      consortia biofilms of major plaque species has established a variety of bacterial
      interactions important in plaque development. In particular, the 'Marsh' nine
      species biofilm consortia systems are powerful quasi steady-state models which
      can be closely specified, modified, and analyzed. In the second approach,
      microcosm plaque biofilms are evolved in vitro from the natural oral microflora
      to the laboratory model most closely related to plaque in vivo. Functionally
      reproducible microcosm plaques are attainable with a biodiverse microbiota,
      heterogeneous structure, and pH behavior consistent with those of natural plaque.
      The resting pH can be controlled by urea supply. Their growth patterns, pH
      gradient formation, control of urease levels by environmental effectors, and
      plaque mineralization have been investigated. Microcosm biofilms may be the only
      useful in vitro systems where the identity of the microbes and processes involved
      is uncertain. Together, these two approaches begin to capture the complexity of
      plaque biofilm development, ecology, behavior, and pathology. They facilitate
      hypothesis testing across almost the whole range of plaque biology and the
      investigation of antiplaque procedures yielding accurate predictions of plaque
      behavior in vivo.

PMID- 9524450
TI  - Methods for microscopic characterization of oral biofilms: analysis of
      colonization, microstructure, and molecular transport phenomena.
AB  - Assessment of the role of biofilm microstructure in biofilm-specific activities
      requires non-destructive measurement techniques for parameterization of
      structural characteristics in parallel with relevant biochemical and
      physiological data. This paper briefly reviews some current methods for biofilm
      structural analysis, with emphasis on new developments in optical imaging and
      mathematical modeling methods. Fluorescence imaging studies of bacterial
      colonization events occurring on exposed model tooth surfaces indicated that
      bacterial adhesion to sessile organisms was of central importance to the early
      colonization process and that this occurred in a non-random manner. Structural
      studies of mature biofilms by confocal microscopy demonstrated the spatial
      distribution of individual species using fluorescent antibodies. Biofilms grown
      under different physiological conditions exhibited differences in structure, and
      methods were developed for parameterizing the spatial orientations of the
      bacteria. Diffusive processes within biofilm microstructures were studied using a
      random walk model in both 2-D and 3-D. Modeling of convective flow within biofilm
      microstructures was achieved by application of lattice Boltzmann methodology.

PMID- 9524451
TI  - The validity of models.
AB  - The ubiquity of biofilm and its classification as a microbial aggregate is
      discussed. Investigations into any microbial ecological problem operate at four
      levels: (i) in situ investigations, (ii) the use of microcosms, (iii)
      experimental model systems, and (iv) mathematical models. Each of these is
      defined and their use in biofilm research illustrated. It is concluded that all
      these approaches are valid and that scientific research in general and biofilm
      research in particular must profit by the use widely different methods if a
      complete understanding of a system is to be achieved.

PMID- 9524452
TI  - Biofilm susceptibility to antimicrobials.
AB  - Microbial biofilms, where organisms are intimately associated with each other and
      a solid substratum through binding and inclusion within an exopolymer matrix, are
      widely distributed in nature and disease. In the mouth, multispecies biofilms are
      associated not only with dental plaque and tooth decay but also with soft tissues
      of the buccal cavity and with most forms of periodontal disease. Organization of
      micro-organisms within biofilms confers, on the component species, properties
      which are not evident with the individual species grown independently or as
      planktonic populations in liquid media. While many of these properties relate to
      the establishment of functional, mixed-species consortia within the exopolymeric
      matrices, others relate to the establishment of physico-chemical gradients,
      within the biofilm, that modify the metabolism of the component cells. A
      consequence of biofilm growth that has profound implications for their control in
      the environment and in medicine is a markedly enhanced resistance to chemical
      antimicrobial agents and antibiotics. Mechanisms associated with such resistance
      in biofilms will form the substance of the present review. While some aspects of
      biofilm resistance are yet only poorly understood, the dominant mechanisms are
      thought to be related to: (i) modified nutrient environments and suppression of
      growth rate within the biofilm; (ii) direct interactions between the exopolymer
      matrices, and their constituents, and antimicrobials, affecting diffusion and
      availability; and (iii) the development of biofilm/attachment-specific
      phenotypes.

PMID- 9524455
TI  - A step forward in paediatric dentistry.

PMID- 9524453
TI  - Specific inhibitors of bacterial adhesion: observations from the study of gram
      positive bacteria that initiate biofilm formation on the tooth surface.
AB  - Oral surfaces are bathed in secretory antibodies and other salivary
      macromolecules that are potential inhibitors of specific microbial adhesion.
      Indigenous Gram-positive bacteria that colonize teeth, including viridans
      streptococci and actinomyces, may avoid inhibition of adhesion by host secretory
      molecules through various strategies that involve the structural design and
      binding properties of bacterial adhesins and receptors. Further studies to define
      the interactions of these molecules within the host environment may suggest novel
      approaches for the control of oral biofilm formation.

PMID- 9524454
TI  - Physiological approaches to the control of oral biofilms.
AB  - Evidence that physiological strategies may be potential routes for oral biofilm
      control has come from (i) observations of the variations in the intra-oral
      distribution of members of the resident oral microflora, (ii) changes in plaque
      composition in health and disease, and (iii) data from laboratory model systems.
      Key physiological factors that were identified as significant in modulating the
      microflora included the local pH, redox potential (Eh), and nutrient
      availability. Increases in mutans streptococci and lactobacilli occur at sites
      with caries; growth of these species is selectively enhanced at low pH. In
      contrast, periodontal diseases are associated with plaque accumulation, followed
      by an inflammatory host response. The increases in Gram-negative, proteolytic,
      and obligately anaerobic bacteria reflect a low redox potential and a change in
      nutrient status due to the increased flow of gingival crevicular fluid (GCF).
      Consequently, physiological strategies for oral biofilm control should focus on
      reducing the frequency of low pH in plaque by (i) inhibiting acid production,
      (ii) using sugar substitutes, and (iii) promoting alkali generation from arginine
      or urea supplements. Similarly, strategies to make the pocket environment less
      favorable to periodonto-pathogens include (i) anti-inflammatory agents to reduce
      the flow of (and hence nutrient supply by) GCF, (ii) bacterial protease
      inhibitors, and (iii) redox agents to raise the Eh locally. Most laboratory and
      clinical findings support the concept of physiological control. However, some
      data suggest that the ordered structure and metabolically interactive
      organization of mature dental plaque could generate a community with a high level
      of homeostasis that is relatively resistant to deliberate external manipulation.

PMID- 9524456
TI  - Glass ionomer materials as a rechargeable fluoride-release system.
AB  - It is well established that glass ionomers (GI) release fluoride (F). The degree
      of F released depends on the physical and chemical properties of the product. In
      the present study the fluoride release and the capacity of the GI to be recharged
      with fluoride was tested for five different brands: XR Ionomer (Kerr), Vitrebond
      (3M), GC Fuji Lining (G.C. Dental Industries Corp.), Baseline VLC (Dentsply) and
      Zinomer (Dent. Mat.). Fifteen test specimens were prepared for each brand. The
      specimens were immersed in deionized water. The F released was measured once a
      day for 11 days. Refluoridation of the test specimens was done with solutions of
      0.02%, 0.04% and 0.2% NaF for 5 minutes on days 11, 16, 21 and 26. The F released
      from recharged specimens was measured daily until day 32. There was a positive
      correlation between the amount of F in the GI and the ability to release F. The
      five materials became 'recharged' with F following repeated F exposure in
      solution, the 0.2% solution being the most effective. XR ionomer released
      significantly more fluoride than any other material and showed the greatest
      ability to be recharged. Zinomer released significantly less fluoride than any
      other material and showed the least ability to be recharged. The present results
      indicate that GI serves as a F reservoir and can act as a prolonged slow-release
      system for at least 32 days.

PMID- 9524457
TI  - Integrity, maintenance and caries susceptibility of sealed surfaces in
      adolescents receiving regular care from general dental practitioners in Scotland.
AB  - Pit and fissure sealants (sealants) are recognized as an effective caries
      preventive measure. The aim of this study was to assess the fate of occlusal
      surface sealants in a sample of 'regularly' attending adolescent patients (mean
      age 12.5 years at baseline) of 41 general dental practitioners, participating in
      a 3-year prospective clinical trial. A subsidiary aim was to compare the caries
      status of completely sealed surfaces with that of inadequately sealed surfaces
      over the same period. Baseline and three annual follow-up examinations were
      conducted by one trained and calibrated examiner under optimal conditions (dental
      chair, operating light, and compressed air). Sealed occlusal surfaces were
      evaluated for sealant type, sealant coverage, and caries status of the surface.
      Data for the initial and final year examinations were available for 402 subjects,
      who had 1377 sealants at baseline. Surfaces with optimal sealant coverage at
      baseline (n = 592) were significantly less likely to have become decayed
      (dentinal caries) or to have been restored by year 4 than surfaces with less than
      complete coverage (P < 0.001). Considering sealant maintenance during the study,
      484 of the sealants were of optimal coverage (covered the fissure system) at the
      final examination. However, only 135 surfaces demonstrated evidence of
      maintenance by attaining optimal coverage. It is concluded that the fissure
      sealants in this sample may not have received the regular maintenance required to
      ensure full surface coverage and thus provide maximal caries protection, as
      inadequately sealed surfaces were more likely to decay than completely sealed
      surfaces.

PMID- 9524458
TI  - The effect of different etching times on the retention of fissure sealants in
      second primary and first permanent molars.
AB  - This study investigated the effect of different etching times on the retention of
      fissure sealants in second primary and first permanent molars. Eighty-four
      children with a total of 144 second primary molars and 264 first molars were
      included in the study. Etching times of 15, 30, 45 and 60 seconds were used. The
      fissure sealants were evaluated at 6 and 12 months. The results showed that the
      overall retention rate of fissure sealants in second primary molars was 73.0% at
      6 months and 64.7% at 12 months, whereas in first permanent molars the retention
      rates were 60.7% at 6 months and 44.1% at 12 months respectively. There was no
      significant difference in the retention of fissure sealants either on second
      primary molars or on first permanent molars at a 6- and 12-month follow-up with
      the different etching times. It was concluded that the different etching times
      did not appear to affect the retention of fissure sealants on the first permanent
      molars or second primary molars. It might therefore be prudent to etch the teeth
      for a much shorter period than conventionally recommended.

PMID- 9524459
TI  - Dental attendance patterns and oral hygiene habits of 5-year-old children in
      Athens and in south London.
AB  - This study compared the dental attendance patterns and oral hygiene habits of 5
      year-old children in the London boroughs of Lambeth, Lewisham and Southwark with
      those in the municipality of Athens in the light of differing provision of oral
      health education. Questionnaires were sent to the parents of 384 children in
      London and 318 children in Athens who took part in a survey of dental health.
      Response rates of 51% and 53% respectively were obtained. More children visit the
      dentist in South London than in Athens, the difference being highly significant.
      In South London the majority of children visit every 6 months, whereas in Athens
      they only visit when they have toothache. More London children brush their teeth
      than Athens children, the difference being significant. Of those brushing in
      London, most brush twice daily. The above findings indicate marked differences in
      dental attendance patterns and oral hygiene habits, and this may be partly
      attributable to differences in the delivery of dental care and oral health
      education in the two countries.

PMID- 9524460
TI  - A case with bilateral paired maxillary supernumerary incisor teeth of
      supplemental and tuberculate form.

PMID- 9524461
TI  - Beckwith-Wiedemann syndrome: dental management.
AB  - Beckwith-Wiedemann syndrome (BWS) comprises multiple congenital anomalies with a
      risk of childhood tumours. Macroglossia is the most common manifestation. Two
      cases are presented to illustrate the importance of early referral and the role
      of preventive dentistry.

PMID- 9524462
TI  - Adenomatoid odontogenic tumour in a 12-year-old boy.
AB  - We present a rare finding of adenomatoid odontogenic tumour (AOT) in a 12-year
      old boy who was referred to the Department of Paediatric Dentistry at the Eastman
      Dental Hospital for the extraction of a carious maxillary permanent molar. First
      presentation revealed that the maxillary right permanent lateral incisor and
      canine were unerupted. Radiological examination revealed a circumscribed
      radiolucent area associated with the distal aspect of the maxillary right
      permanent lateral incisor. The patient was admitted to our Day Care Unit where
      the carious maxillary molar was extracted and the radiolucent area associated
      with the maxillary right permanent incisor was explored. Pathological examination
      confirmed the lesion as adenomatoid odontogenic tumour. We present a brief review
      of the literature and consider how differential diagnosis of this tumour from
      more common odontogenic lesions can be established.

PMID- 9524463
TI  - Regional odontodysplasia: report of four cases.
AB  - Four cases of regional odontodysplasia are described. Clinically erupted teeth
      appear hypoplastic and are often mobile. The radiographic appearance has given
      rise to the term 'ghost teeth' and the cases presented demonstrate this with
      short roots which are less well calcified than normal teeth. Clinical and
      radiographic findings showed that this condition affects only one side of the
      jaw, but can be seen in any part of the upper or lower jaws. This article
      represents cases in different parts of the mouth with varying degrees of
      involvement.

PMID- 9524464
TI  - Oral self-mutilation by a 17-month-old child with Lesch-Nyhan syndrome.
AB  - We report a 17-month-old boy who was a known case of Lesch-Nyhan syndrome and
      presented with self-inflicted oral ulcerations of his lips and cheeks. He had a
      normal complement of caries-free deciduous teeth. Initially a conservative
      approach was planned and a bite plate made, but as a result of poor compliance
      and persistent ulceration and after consultation with his parents it was decided
      to extract all deciduous teeth.

PMID- 9524465
TI  - Pattern of agenesis in the primary dentition: a radiographic study of 193 cases.
AB  - The purpose of this study was to examine radiographs of a large sample of
      children who had congenital absence of primary teeth and to determine the number
      and distribution of the missing teeth. Radiographs collected within the Danish
      Municipal Child Oral Health Care System were available of 193 children, all of
      whom had congenital absence of one or more primary teeth but no other
      abnormalities in the jaws or dentition. More than half of the children (54.9%)
      had agenesis of only one primary tooth, and 7.8% of more than two primary teeth.
      Agenesis was found twice as frequently in the maxillary lateral incisor region
      (119 children) than in the mandibular lateral incisor region (53 children).
      Congenital absence of primary molars, canines and maxillary central incisors was
      extremely rare. However, agenesis of one maxillary primary central incisor was
      found in two cases. A follow-up study will compare the agenesis patterns recorded
      with the pattern of agenesis in the permanent dentition of the same group of
      children.

PMID- 9524466
TI  - The effect of biannual applications of amine fluoride solution on caries
      incidence in permanent first molars: a 5-year study.
AB  - A randomized double-blind clinical trial was undertaken in a non-fluoridated
      community to assess the effectiveness of a minimal preventive intervention based
      on biannual applications of an amine fluoride (AmF) solution containing 1%
      fluoride. A total of 284 schoolchildren aged 6 years were recruited from a
      primary school in Milan, Italy, and randomly assigned to an experimental or a
      control group. The subjects of the experimental group received two applications
      each year of AmF to the permanent first molars and the control group subjects
      received similar applications of a placebo solution. Both in the experimental and
      control groups caries experience (DMFT) of the first molars was recorded every 6
      months for 5 years. The mean DMFT scores in the experimental and control group
      were, respectively, 0.56 and 0.22 at the beginning and 1.14 and 1.75 at the end
      of the study. The preventive effect of the treatment became statistically
      significant only after 3 years. Survival analysis performed on the first molars
      that were sound at baseline showed that the topical AmF treatment caused, after 5
      years, a significant reduction of caries incidence. This result confirms
      observations found in the international literature on the anticaries action of
      AmF. The administration rate used in this study seems to be useful for community
      preventive applications as it reduces the total amount of fluoride administered
      and the potential risks, and involves few personnel.

PMID- 9524467
TI  - Tooth bud extraction and rubbing of herbs by traditional healers in Tanzania:
      prevalence, and sociological and environmental factors influencing the practices.
AB  - The practice by traditional healers in Tanzania of extracting tooth buds or of
      rubbing herbs on to the gingivae of young children to cure fevers and diarrhoea
      has been known for many years. The aim of this study was to determine the
      prevalence of these practices in different regions of Tanzania and to identify
      sociological and environmental factors influencing belief in their efficacy. A
      total of 1052 children were examined for missing primary teeth, or scars or
      wounds on the gingivae, resulting from tooth bud extraction. In addition, 268
      parents of children who had received treatment from a traditional healer were
      interviewed to identify factors that led them to go to a traditional healer. The
      prevalence of tooth bud extraction in villages in which tooth bud extraction was
      first reported in the early 1980s was 0.5%, and in villages in which the practice
      was only recently reported it was 60%; the prevalence of rubbing herbs was 32%
      and 0.4%, respectively. Persistent fevers and diarrhoea were the major symptoms
      which led parents to go to a traditional healer. However, 60% of the parents had
      taken their child to a hospital before going to a healer; 72% of these had
      attended at least three times but only 5.5% reported that the treatment given in
      the hospital cured the condition. It is recommended that intensive health
      education on the causes, treatment and prevention of fevers and diarrhoea should
      be instituted, in conjunction with effective management of these conditions in
      hospital facilities.

PMID- 9524469
TI  - Benign mucous membrane pemphigoid presenting as desquamative gingivitis in a 14
      year-old child.
AB  - A 14-year-old girl presented with painful, erythematous gingivae, which
      occasionally developed blisters. There were no other mucosal or skin lesions.
      Clinical, histopathological and immunofluorescence studies suggested a diagnosis
      of benign mucous membrane (cicatricial) pemphigoid, presenting as desquamative
      gingivitis. Benign mucous membrane pemphigoid in childhood is rare and only a few
      cases with exclusive oral mucosal involvement have been reported in the
      literature. The desquamative gingivitis responded well to a topical steroid
      regimen.

PMID- 9524468
TI  - Infraocclusion of primary molars in monozygotic twins: report of two cases.
AB  - Genetic factors have been implicated in the aetiology of infraocclusion, but only
      three published reports describe infraocclusion of primary molars in twins. This
      case report describes the occurrence of infraocclusion in two pairs of twins. The
      distribution of affected teeth and the severity of infraocclusion were strikingly
      similar in each pair. The report provides further evidence of a genetic
      contribution to the aetiology of the condition, and also highlights the need to
      examine siblings, and especially twins, of children who present with an
      infraoccluded primary tooth.

PMID- 9524470
TI  - Bleaching of a discoloured non-vital tooth: use of a sodium perborate/water paste
      as the bleaching agent.
AB  - Bleaching materials containing hydrogen peroxide have been used successfully for
      the treatment of discoloured non-vital teeth; however, their use has occasionally
      been associated with external root resorption. Some evidence exists that sodium
      perborate mixed with water is as effective as sodium perborate mixed with
      hydrogen peroxide. A case is presented which supports this and a step-by-step
      technique is described.

PMID- 9524471
TI  - Maxillofacial injuries in 209 Libyan children under 13 years of age.

PMID- 9524472
TI  - The oral and dental status of children residing in a Romanian orphanage.

PMID- 9524474
TI  - History of the International Association of Paediatric Dentistry. Part 10: A
      final miscellany.

PMID- 9524473
TI  - Caries experience of 5-year-old children in Alkharj, Saudi Arabia.

PMID- 9524475
TI  - Mastering the precision removable partial denture. Part Two. Connection of
      partial dentures to the abutment teeth.
AB  - Because the arrangement of the remaining dentition may vary tremendously, the
      design of a removable partial denture is complicated with regard to function,
      esthetics, hygiene and oral comfort. Part One of this article, published in the
      January/February issue of JDT discussed how disassembling the RPD into its
      structural components and defining their functions could help the dental
      technician with RPD planning. Part two discusses the connection of partial
      frameworks to the remaining dentition and breaks down the components of a
      combination case.

PMID- 9524476
TI  - Gold Electroforming System: GES restorations.
AB  - The use of electrolysis as a means of forming a substructure for porcelain-fused
      to-metal inlays, onlays, full crowns and even bridges has many advantages over
      the use of cast metal. Composed of pure gold deposited directly onto a duplicate
      die, electroformed copings have a high degree of biocompatibility and accuracy
      for increased durability (photograph 18). The internal surfaces of the coping
      match the exterior of the duplicate die exactly, and the thickness of the
      material deposited is a uniform 0.2mm. Marginal accuracy on completed
      restorations is on average 19 microns. The gold has the added advantage of
      burnishability. Recent developments in equipment and technique have placed this
      form of substructure well within the scope of consideration for most ceramics
      laboratories.

PMID- 9524477
TI  - Laboratory procedures for fabricating pressable all-ceramic restorations.
AB  - Part 1 of this article covered the applications, preparation requirements, and
      procedures through divesting for the pressable ceramic system. The O.U. (opacity
      units) system was also described, and how it relates to the proper selection of
      core material.

PMID- 9524478
TI  - Broken abutment: troubleshooting implants.

PMID- 9524479
TI  - Implant-retained overdenture prosthesis.

PMID- 9524480
TI  - Ten steps to creative decision making.

PMID- 9524481
TI  - Patient swallows removable partial denture: a clinical report.
AB  - The indications for a unilateral partial denture would appear to be when there is
      a single posterior tooth missing, bound on both sides by usable abutments.
      Another consideration for a unilateral partial denture is that the patient does
      not want to restore the space with a fixed partial denture. One drawback to this
      treatment modality is that the prosthesis needs to be removed after each meal and
      cleaned. Other more important reasons for not making a 1-tooth removable partial
      denture is that it provides no cross-arch stabilization and there is the chance
      that it may be swallowed if it becomes dislodged. This clinical and laboratory
      report describes how this patient was treated.

PMID- 9524482
TI  - Laboratory procedures for fabricating pressable all-ceramic restorations.
AB  - All-ceramic restorations have been recognized and accepted as being esthetically
      superior to porcelain-fused-to-metal or all-cast restorations. However, gains in
      esthetics achieved with an all-ceramic crown often meant sacrifices in strength,
      fit or both. Recent developments in the pressed ceramic format continue to secure
      the pressed all-ceramic restoration as a viable alternative to porcelain-to-metal
      and all-cast restorations. This article focuses on the most updated techniques
      and considerations of this type of system and its effectiveness in providing
      esthetics, strength and fit through "technician-friendly" procedures, materials
      and equipment.

PMID- 9524483
TI  - ISO: setting standards that ensure quality and save money.

PMID- 9524484
TI  - Gold color in dental alloys.
AB  - This article will help the dental laboratory with alloy selection by exploring
      how the relationship among color, ductility and strength applies to gold and how
      color can be quantified. Because higher quality materials translate into higher
      profits, upselling to the dentist and patient is also discussed.

PMID- 9524485
TI  - Mastering the removable partial denture. Part one: Basic reflections about
      construction.
AB  - Because the arrangement of the remaining dentition may vary tremendously, the
      design of a removable partial denture is complicated with regard to function,
      esthetics, hygiene and oral comfort. Part One of this article will discuss how
      disassembling the RPD into its structural components and defining their functions
      will help the dental technician with RPD planning. Part Two will break down the
      components of a combination case using the same systematic approach.

PMID- 9524486
TI  - Following a rigid plan and treatment protocol will maximize dental implant
      success--Part II.

PMID- 9524487
TI  - Dental technology. Part. II Standards.

PMID- 9524489
TI  - Overdenture retention and stabilization with ball-and-socket attachments:
      principles and technique.
AB  - Implant attachments of various designs are used to retain, stabilize and
      sometimes support overdentures. Tissue supported overdentures stabilized and
      retained by two to four implants are often the restorations of choice due to
      patient preference, limitations in finances, insufficient available bone to
      accommodate a greater number of implants, or needed improvements in esthetics,
      phonetics and oral hygiene. Female retentive sockets in the overdenture base that
      snap onto male ball abutments offer such advantages as reduction in hydraulic
      resistance to coupling, lower functional stress on the implants, retention that
      can be adjusted downward, easy component replacement and only relatively parallel
      abutments.

PMID- 9524488
TI  - Retirement planning made simple.

PMID- 9524490
TI  - Eye protection in dental laboratories.
AB  - Many dental laboratory procedures increase the chances of serious eye injury.
      This would include traumatic injuries due to projectiles or through exposure to
      harsh chemicals or heat and infections from contact with patient body fluids. To
      help assure a safer working environment, awareness of the need for eye protection
      must be established and maintained by all laboratory personnel. The purpose of
      this article are: 1) to list the applicable federal regulations concerning eye
      safety in dental laboratory workplaces; 2) to describe the various types of
      appropriate eyewear; and 3) to identify which protective devices best prevent
      exposure to specific types of hazards. The goal of this article is to help dental
      laboratories with their employee safety programs, especially concerning the
      selection of protective eyewear. Such programs must include engineering controls
      and work practice controls plus appropriate personal protective equipment.
      Laboratories today must comply with safety mandates in the most effective and
      efficient manner.

PMID- 9524491
TI  - Investing: how to get started.

PMID- 9524492
TI  - The origin of the Internet as I imagine it to be loosely based on history.

PMID- 9524493
TI  - Following a rigid plan and treatment protocol will maximize dental implant
      success--Part I.
AB  - A properly established protocol ensures success when providing implant therapy
      for the dental patient. The basis for achieving doctor/patient objectives
      emphasizes esthetics, phonetics, function, longevity and maintainability. Too
      often patients are presented with completed prosthetics without prior
      consideration of their expectations. This article identifies and describes each
      phase of pre- and post-surgical planning and the role of each implant team
      member. The goal of this article is to illustrate the value of utilizing specific
      treatment protocols to guide the restoring dentist, surgeon, technician and
      patient toward predictable results while minimizing uncertainties.

PMID- 9524494
TI  - Dental technology standards.

PMID- 9524495
TI  - Invest! Your retirement clock is ticking.

PMID- 9524497
TI  - Effect of dexamethasone on osseointegration: a preliminary experimental study.
AB  - The peri-implant reparative process is one of the factors involved in
      osseointegration. Local and systemic factors may contribute to the peri-implant
      micro-environment. The aim of this study was to assess the effect of
      dexamethasone (DXM) on the first stages of the post-implantation reparative
      process using a quantitative osseointegration experimental model previously
      developed at our laboratory. A titanium laminar implant was inserted into the
      right tibiae of nine male Wistar rats under ether anesthesia, following a
      technique we previously described. Six rats received 120 micrograms/kg/day i.p.
      doses of DXM (Decadron Sidus, Argentina) for 14 days pre-implantation and 14 days
      post-implantation. The remaining three (controls) were injected with an
      equivalent volume of saline. On day 14 post-implantation, all animals were
      killed, and their tibiae were resected, radiographed, and processed before being
      embedded in methylmethacrylate. Microscopic observation and histomorphometric
      studies were performed. Results show that, in this experimental model, the
      extension of osteogenic peri-implant response was greater in DXM-treated animals
      than in controls. Thus, our laminar implant test may prove useful to study the
      effects of corticosteroids on the osseointegration process.

PMID- 9524498
TI  - Practitioner-patient communication software: an aid in the prescription of dental
      prostheses.
AB  - A questionnaire designed for psychometric evaluation was used to develop
      communication software that helps us understand patients' expectations of their
      prostheses. This enables the practitioner to select and suggest the type of
      prosthesis that best responds to the hopes, as well as the needs, of patients. At
      the end of the treatment process, the practitioner is able to ascertain whether
      the patient's expectations have indeed been met. With this software, we can also
      compare various types of prostheses based on evaluation by patients as well as
      conduct multi-center studies.

PMID- 9524496
TI  - Demineralized bone matrix supplied by bone banks for a carrier of recombinant
      human bone morphogenetic protein (rhBMP-2): a substitute for autogeneic bone
      grafts.
AB  - Four commercially available preparations of demineralized freeze-dried human bone
      powders (DFDB) were investigated for endogenous bone morphogenetic protein (BMP)
      as observed by osteoinductive activity. Composites of DFDB without and with 1
      microgram or 10 micrograms of recombinant human bone morphogenetic protein-2
      (rhBMP-2) were implanted into the hindquarter muscles of Swiss-Webster mice. The
      four batches of DFDB without rhBMP-2 were placed also in hindquarter muscles of
      athymic mice. Three weeks after implantation, the area of induced bone and
      cartilage formation was measured by radiographic and histomorphometric methods.
      In normal mice, without rhBMP-2, DFDB implants induced development of dense
      fibrous connective tissue with minimal, if any, new bone. In athymic mice, DFDB
      induced development of small patches of appositional new bone. In contrast, in
      normal mice, composites of DFDB and rhBMP-2 induced development of large areas of
      heterotopic bone and bone marrow formation. The bone morphogenetic response
      occurred with a statistically significant difference (p < 0.0001) between
      implants of 1 microgram and the 10-microgram rhBMP-2 composites. Thus, DFDB from
      all four bone banks demonstrated comparable capacity to serve as a carrier for
      rhBMP-2.

PMID- 9524499
TI  - Post-insertion peri-implant tissue assessment: a longitudinal study.
AB  - The peri-implant gingivae act as a biological barrier that prevents the ingress
      of plaque bacteria, oral debris, and saliva components into the internal
      environment of the jaw. The integrity of this barrier around a total of 163 Steri
      Oss HA-coated threaded root-form implants placed in 48 patients was examined at
      six-month intervals over a 42-month time period, beginning at the time of final
      prosthetic placement. Five clinical parameters for tissue assessment were used:
      Mean Implant Sulcus Readings (MISR), Muhlemann Sulcus Bleeding Index (SBI),
      Miller's Mobility Index (MI), bone loss readings (BL), and gingival condition
      (GI). Bone loss and mobility were negligible throughout the 42-month study
      period. At six months post-insertion, 58.6% of the Mean Implant Sulcus Readings
      exceeded 4 mm. Gingival conditions and bleeding response also were non-ideal in a
      significant number of cases (52.9 and 62.1%, respectively). However, all three of
      these assessments later showed dramatic improvement. Patients' inability to
      "deplaque" their newly acquired implant prostheses effectively may be a factor
      contributing to the high incidence of undesirable pocket depths and non-optimal
      gingival appearance at the first six-month assessment point. Attainment of the
      necessary skills may account for the improved readings at the later evaluations.

PMID- 9524500
TI  - Rapid bone resorption adjacent to hydroxyapatite-coated implants.
AB  - This paper describes rapid bone resorption in the peri-implantitis of HA implants
      based on both our clinical observations of and histological research on extracted
      dense hydroxyapatite (HA) implants. The surfaces of extracted HA implants were
      rough, although they were smooth at fixture placement. Plaque formed on the necks
      of the implants, whereas little plaque was seen on the bottoms. The plaque
      consisted of cocci and rods, including filamentous bacteria. Few spirochetes were
      observed. Although surrounding bone was formed rapidly around the HA implant,
      bone thickness gradually decreased compared with the titanium implant. These
      facts suggest that the rigid biointegration of HA with the thin surrounding bone-
      that is, the overstressing of the bone--causes rapid bone resorption rather than
      plaque accumulation on HA.

PMID- 9524501
TI  - Implant-supported single-tooth replacements: risk of implant and prosthesis
      failure.
AB  - Data from 236 patient cases of implant-supported single-tooth replacements in the
      maxillary anterior region were sequentially recorded and documented. The time in
      situ ranged from a minimum of five to a maximum of 19 years. Twenty-two implants
      failed during the observation period. The causes of such failure were peri
      implantitis, implant fracture, and trauma. The probability of success according
      to the Kaplan-Meier method decreased to 0.89 over a period of 10 years. The
      failure rate for implants replacing lateral incisors was lower than that for
      implants replacing central incisors. Seventy-six cases were clinically documented
      for 10 years or more. In 15 cases, replacement of the prosthetic superstructure
      was necessary during the 10-year period. The course of therapy and clinical
      follow-up care is described by a multi-state distribution.

PMID- 9524502
TI  - Clinical evaluations of a porous-surfaced endosseous implant system.
AB  - Clinical evaluations of a new porous-surfaced implant concept (Endopore) in a
      large population of fully and partially edentulous patients are reported, and a
      technique of spreading buccal and lingual plates with osteotomes to place these
      implants in proximity to the sinus of the posterior maxilla is described. Three
      dimensional, interconnecting pores on this implant's bone interface surface give
      a great surface area for bone engagement. When the maxilla is prepared by this
      spreading procedure, these implants can be successfully placed in areas having
      limited available bone. Our success rates are 97.0% for implants stabilizing a
      mandibular overdenture and 94.8% for implants placed in partially edentulous
      patients. Many times, sinus lift or other augmentation procedures can be avoided
      in the maxilla and mandible, allowing for less patient morbidity and for an
      implant reconstruction that is more affordable for the patient.

PMID- 9524503
TI  - Helical CT scanning for CAD/CAM subperiosteal implant construction.
AB  - Subperiosteal implant is the treatment of choice for the fully or partially
      edentulous atrophic mandible if grafting procedures are not contemplated to give
      the jaw sufficient available bone for endosseous implants. The main disadvantage
      of the standard technique for the construction of this implant is that it
      requires two surgical procedures. However, it is an accepted and proven technique
      with a long-term survival rate. This paper discusses the use of the CT scan
      subperiosteal implant, which provides a result similar to that of the standard
      subperiosteal implant, but requires only one surgical procedure. The accuracy of
      fit of the CT scan subperiosteal implant is similar to that of the implant
      fabricated by means of a standard two-surgical-impression technique. New updated
      CT scan machines use faster helical scanners and offer a great improvement over
      previous CT scan machines. The new CT scan machines reduce the chance of patient
      movement, produce a more accurate CT scan, and enable a more accurate model of
      the mandible or maxilla to be developed. This paper discusses the production of a
      well-fitting CT scan subperiosteal implant by a trained, knowledgeable, and
      cooperative team of dentist, CT scan technician, and radiologist, all of whom
      understand the technical means to achieve their goal.

PMID- 9524504
TI  - A modified occlusal registration and implant transfer technique.
AB  - The technique for the transfer of implant and abutment position to a working cast
      has been hindered by multiple transfers and record reproductions. These serve
      only to delay completion of the patient's prosthetic requirements. A transfer
      technique that uses custom impression trays fabricated from surgical templates
      allows for a single-visit transfer of centric occlusion, vertical dimension,
      tooth position, and implant or abutment location in one procedure. This
      streamlines treatment and allows for quicker delivery of final prostheses.

PMID- 9524505
TI  - Osseointegration for welded and cast prostheses: presentation of two cases.
AB  - The author describes two cases of full dental arches with only a few natural
      teeth in place that were treated with multi-dimensional, osseointegrated
      implants. The former case utilized the technique of titanium casting of the caps
      on natural teeth and on implants, with intra-oral welding of the caps to the
      implants. In the latter case, the techniques of welding and casting differ.

PMID- 9524506
TI  - Fluid pressure may cause periprosthetic osteolysis. Particles are not the only
      thing.
AB  - Early prosthesis migration predicts late clinical failure, as also does the shape
      or position of, e.g., a femoral stem. These factors appear unrelated to wear
      particles. Thus, the initiation of the loosening process has other causes. After
      this process has started (i.e., the prosthesis migrates), particles may play a
      role, at least by inhibiting new bone formation at the membrane, but the
      hypothesis of pressure-induced bone resorption appears easier to support by
      animal experiments and accords with mechanical risk factors.

PMID- 9524507
TI  - Short periods of oscillating fluid pressure directed at a titanium-bone interface
      in rabbits lead to bone lysis.
AB  - Fluctuating high fluid pressures have been reported in pseudojoints after total
      hip arthroplasty, and may be present throughout the effective joint space. When
      the pressure extends locally to the bone implant interface, we hypothesized that
      it might have led to bone resorption. We developed an experimental implant model
      to study whether oscillating fluid pressure, applied during 2 hours a day, can
      lead to osteolysis at the bone implant interface. 12 mature rabbits received a
      titanium implant, which was allowed to osseointegrate. Thereafter, fluid pressure
      was applied to a specific area of the titanium bone interface at the periosteal
      side of the cortex in 6 of the rabbits. The pressure, applied during 2 hours a
      day for 14 days, oscillated between 70 and 150 mm Hg, with a frequency of 0.1 Hz.
      Bone resorption was not found in any of the control animals, but it occurred
      under 4 implants exposed to fluid pressure (p = 0.03; Fisher's exact test).
      Localized osteolytic lesions had developed, with evidence of osteocyte death in
      the surrounding cortical bone. In 1 of the 2 specimens without osteolysis, there
      was evidence of fluid leakage into the soft tissues. In 4 specimens (3 with and 1
      without osteolysis), bone formation was observed at the endosteal side opposite
      to the pressure zone. This did not occur in the controls. No signs of infection
      were observed. Our findings indicate that oscillating fluid pressure, even when
      present only during short periods, can lead to osteolysis and may be a cause of
      prosthetic loosening. Endosteal bone apposition may be a result of the
      interstitial flow that was created, giving false signals of mechanical load to
      the osteocytes.

PMID- 9524508
TI  - THA revision with extensively porous-coated stems. 32 hips followed 2-6.5 years.
AB  - Since 1991, we have used 32 extensively porous-coated femoral stems with
      cylindrical distal cross-section for revision of failed cemented stems. At an
      average follow-up of 4 years, one stem had been re-revised due to a
      periprosthetic femoral fracture, but no aseptic loosening has been observed. The
      average postoperative Harris Hip Score was 84 points. Radiographically, 23 stems
      were well fixed with bone-ingrowth, which was mostly observed in the distal
      portion of the porous coating. Increased thickness and density of the thin
      cortical wall was also seen. Mild stress shielding was present in 4 cases, but
      was not progressive and gave no symptoms. An extensively porous-coated stem, with
      a cylindrical distal cross-section, seems to be a reasonable choice in femoral
      revision.

PMID- 9524509
TI  - Failed hip prostheses in hemodialysis patients. Amyloid deposition at the bone
      implant interface in 4 cases.
AB  - 4 hemodialysis patients with failed bipolar hip prostheses underwent 6 revision
      arthroplasties. Their average age was 55 years, the average duration of
      hemodialysis was 14 years and the average interval from the primary arthroplasty
      to revision was 7 years. The interface membranes revealed amyloid deposits in all
      specimens. There were few polyethylene wear particles, and cement debris or
      foreign body reactions were rare. It appears that amyloid may cause osteolysis
      and early prosthetic loosening.

PMID- 9524510
TI  - Acetabular development after open reduction for developmental dislocation of the
      hip. 15-year follow-up of 22 hips without additional surgery.
AB  - We reviewed serial radiographs of 22 hips in 20 patients with developmental
      dislocation of the hip (DDH), who were treated by open reduction and followed
      without additional surgery until puberty, to identify predictive measures of
      subsequent acetabular development. The average age at surgery and at final follow
      up was 14 (5-26) months and 15 (13-20) years, respectively. Hips with a CE angle
      above 20 degrees and femoral head coverage above 75 degrees at the final follow
      up were classified as "satisfactory outcome". At the final follow-up, 14 hips
      were classified as satisfactory and 8 hips as unsatisfactory. In the former
      group, acetabular improvement continued throughout growth, whereas in the
      unsatisfactory group, the acetabulum did not improve after 3-5 years of age.
      Unsatisfactory condition at the final follow-up was noted in all hips that had a
      CE angle less than 0 degrees and head coverage less than 50%, when the patients
      were 3-5 years old and less than 5 degrees and 60%, respectively, at the age of 6
      8 years. These findings should be useful in assessing the need for and the timing
      of acetabuloplasty after open reduction for DDH.

PMID- 9524511
TI  - Ultrasound measurements of the newborn hip. Comparison of two methods in 657
      newborns.
AB  - We compared ultrasound measurements using the Graf and Terjesen methods in 657
      newborns. The alpha angle and femoral head coverage (FHC) were analyzed. The rate
      of DDH was 3.9%, according to Graf and 2.9%, according to Terjesen. The
      spontaneous increases in alpha angle and FHC were 5 degrees and 7%, respectively,
      during the first 2 months. Good accordance between the two methods was shown. A
      few hips were normal, according to one method and were subluxated, according to
      the other one. The methods gave similar results, except the percentage of
      "immature hips" IIa (29%) and "possible dysplastic hips" (14%). This might be a
      sign of better specificity of the Terjesen method. Good interosberver agreement
      and simple classification favor use of the Terjesen method. The method of Graf is
      the most commonly used and gives adequate evaluation of the hip, if the method of
      examination and rather complicated classification are followed closely.

PMID- 9524512
TI  - RAB-plate vs Richards CHS plate for unstable trochanteric hip fractures. A
      randomized study of 233 patients with 1-year follow-up.
AB  - We prospectively randomized 233 patients with unstable trochanteric hip fractures
      for treatment with a 120 degrees fixed angle blade-plate having a buttress rod
      (group A, n 111) or a 135 degrees compression hip screw (group B, n 122). The
      minimum follow-up time was 1 year. The ratio of technical failure was 9% in group
      A and 19% in group B (p = 0.06). 79 (87%) fractures in group A and 65 (68%)
      fractures in group B healed without any complication (p = 0.003). Malunion
      occurred in 2 cases in group A and in 15 cases in group B (p = 0.002).

PMID- 9524513
TI  - Transarticular tumor invasion via ligamentum teres. A clinical-pathologic study
      of 12 patients.
AB  - We studied 12 patients who were operated on for malignant tumors in and around
      the hip joint. A correlative study, including preoperative staging studies and
      anatomical-pathologic aspects of the hip joint, was performed. In 4 of the 12
      patients, we found direct histologic evidence of tumor invasion from the head of
      the femur through the ligamentum teres to the acetabular fovea and vice versa. It
      seems that the ligamentum teres is a potential route for transarticular spread of
      a tumor.

PMID- 9524514
TI  - Postoperative blood salvage in hip and knee arthroplasty. A prospective study on
      cost effectiveness in 161 patients.
AB  - We conducted a prospective controlled study on 161 patients who underwent primary
      or revision total hip or knee arthroplasty to assess the efficacy and limitations
      of postoperative blood salvage. The actual quantity of blood salvaged after
      washing, the theoretical increase in hemoglobin concentration caused by its
      reinfusion and the cost of this procedure were studied. The mean amount of packed
      red cells after washing was 117 g. The average increase in hemoglobin
      concentration, which theoretically would have been achieved by retransfusion, was
      0.47 g/dL. One third of the devices used were discarded as not effective enough
      and, in order to obtain an increase of 1 g/dL in the hemoglobin concentration, an
      average of 3.4 postoperative Solcotrans Plus Orthopaedic devices were used. To
      obtain the same increase in hemoglobin concentration as that given by an
      allogeneic blood transfusion, the overall cost of materials alone was more than
      five times the price of a single blood unit transfusion.

PMID- 9524515
TI  - Patient survival after total knee arthroplasty. 5-year data in 926 patients.
AB  - We analyzed prospectively the 5-year survival in 926 patients undergoing 1,024
      total knee arthroplasties (TKA) in the period February 1989-December 1990. The
      patients were compared to an age- and sex-matched general population and to 326
      patients operated on in the same period with total hip arthroplasty. Cox analysis
      showed that male sex, rheumatoid arthritis and complications within the first
      year increased the mortality rate in the TKA group. When this group was compared
      to the general population, only rheumatoid patients aged 65-74 years had an
      increased mortality. Generally, the TKA patients had a longer survival than the
      general population, especially women > 75 years old with arthrosis. The
      cumulative 5-year patient survival was 89%, both after hip and knee arthroplasty
      and was 81% in the matched general population.

PMID- 9524517
TI  - Adult ankle fractures--an increasing problem?
AB  - The epidemiology of ankle fractures is changing. Increasing longevity has
      resulted in the highest age-specific incidence of ankle fractures being in women
      between 75 and 84 years of age. The introduction of the AO classification has
      facilitated analysis of the commonest fracture types. This survey of 1,500 ankle
      fractures, seen in a 3-year period in the Edinburgh Orthopaedic Trauma Unit,
      shows that the commonest ankle fractures are the B1.1 and A1.2 lateral malleolar
      fractures. Isolated malleolar fractures accounted for two thirds of the series,
      with bimalleolar fractures occurring in one fourth of the patients and
      trimalleolar fractures in the remaining 7%. Open fractures occurred in 2%.

PMID- 9524516
TI  - Comparison of biodegradable and metallic tension-band fixation for patella
      fractures. 38 patients followed for 2 years.
AB  - We compared the outcome of patella fractures fixed by biodegradable tension-band
      (B) with self-reinforced polyglycolide or self-reinforced poly-L-lactide plugs
      and polyester ligaments or by metallic tension-band (M) with Kirschner wires and
      metallic cerclage wire in a randomized study. 38 fractures (18 with B and 20 with
      M) were treated. The follow-up time was 24 (14-32) months. The fractures healed
      in all patients after a medium of 8 weeks. In the B group, the clinical outcome
      was good in 13, fair in 4, and poor in 1 patient. In the M group, the
      corresponding figures were 15, 3 and 2. There were no clinical or radiographic
      differences between the two methods. Patella fractures can be treated,
      successfully using biodegradable tension-band fixation with no need for a second
      operation to remove the implants after bone union.

PMID- 9524518
TI  - Epidemiology of ankle fractures. A prospective population-based study of 212
      cases in Aalborg, Denmark.
AB  - We studied the epidemiology of ankle fractures prospectively during 1 year in a
      population of about 200,000. The overall incidence rate was 107 fractures per
      10(5) person-years. Below the age of 50, ankle fractures were commonest in men.
      After this age, females became predominant and the age-specific incidence rates
      decreased in both sexes. The main cause of fracture was falls (87%), on the
      ground, on stairs or from a height. 137 fractures (55%) occurred in sports, play
      or other leisure activities. Most patients (64%) were walking, running or jumping
      at the time of injury. Alcohol and slippery surfaces were each involved in nearly
      a third of the cases. The distribution of the fractures according to both the
      Lauge-Hansen and the AO Weber classification systems were within the limits of
      previous series. Nearly half the patients were hospitalized and the fractures
      were operated on with osteosynthesis. Our findings indicate that ankle fractures
      are mainly caused by substantial trauma sustained during physical activity.
      Osteoporosis seems to be of minor importance.

PMID- 9524519
TI  - Lateral ankle ligaments and tibiofibular syndesmosis. 13-MHz high-frequency
      sonography and MRI compared in 20 patients.
AB  - To test the ability of ultra-high frequency ultrasound (13 MHz scanner) to
      distinguish between intact and ruptured ligaments on the lateral side of the
      ankle, we examined 20 patients with an acute inversion injury with MRI and
      ultrasound. When judged by the MRI diagnosis, an injured anterior talofibular
      ligament was correctly diagnosed by ultrasound in 13 of 14 and an intact anterior
      talofibular ligament in 5 of 6 patients. In the case of the calcaneofibular
      ligament, 4 ruptured and 16 intact ligaments were diagnosed equally well with
      both methods. The injured anterior tibiofibular ligament was correctly diagnosed
      by ultrasound in 6 of 9 patients, while the intact ligament was correctly
      recognized in 10 of 11 patients. Our findings indicate that it is possible to
      distinguish injured from intact ligaments sonographically.

PMID- 9524520
TI  - Articular cartilage repair. Rabbit experiments with a collagen gel-biomatrix and
      chondrocytes cultured in it.
AB  - To repair a full-thickness articular cartilage defect in rabbit knees, we
      developed a technique of using a collagen gel hardened by cultured allogeneic
      chondrocytes in it. The gel-chondrocyte composite accumulated an intense
      metachromatic matrix, and had elasticity and stiffness enough to be shaped easily
      after 2 weeks' culture in vitro. It was implanted into full-thickness articular
      cartilage defects. Histologic evaluation was performed up to 6 months after
      surgery, using a histologic grading scale composed of 5 categories. In the gel
      chondrocyte composite implanted group, good repair was observed from as early as
      1 day up to 6 months. On the other hand, in the empty control group, no repair
      was observed 1 day to 2 weeks after the defects were made. At 4 weeks, some
      repair occurred, but even at 6 months the repair was not good.

PMID- 9524521
TI  - Human bone bank allografts stimulate bone resorption and inhibit proliferation in
      cultures of human osteoblast-like cells.
AB  - Incorporation of a frozen human bone allograft requires osteoclast activity and
      ingrowth of recipient osteoblast precursors. We examined the effects of
      allografts on human osteoblasts. Allografts stimulated a release of factors from
      normal human osteoblast-like cells, capable of inducing osteoclastic bone
      resorption in vivo. Further allografts inhibited osteoblast proliferation in
      cultures. The response was detectable within 4 days of culture and was still
      present after 3 weeks. Devitalized bone autografts had a similar effect. This
      suggests that bone bank grafts may induce a resorptive reaction at the recipient
      site by stimulating release of factors from osteoblasts capable of inducing
      osteoclastic resorption. The storage temperature was crucial for preservation of
      the response, since the activity was lower in allografts stored for 6 months at 
      20 degrees C than in those stored at -80 degrees C.

PMID- 9524522
TI  - Trapezius transfer for shoulder paralysis. 6 patients with brachial plexus
      injuries followed for 1 year.
AB  - We transferred the trapezius with its bone insertion to the proximal humerus in 6
      patients for treatment of a paralytic shoulder secondary to traumatic lesions of
      the brachial plexus. After 1 year, the shoulder abduction was improved from
      average 13 degrees (0 degrees-30 degrees) preoperatively to 76 degrees (50
      degrees-100 degrees) postoperatively, and the shoulder flexion from 18 degrees (0
      degrees-40 degrees) to 78 degrees (45 degrees-110 degrees) postoperatively. All
      the patients were satisfied with the outcome. We consider that transfer of the
      trapezius in a paralytic shoulder after brachial plexus injury gives a better
      outcome than shoulder fusion.

PMID- 9524523
TI  - Corrective ulnar osteotomy for malunited anterior Monteggia lesions in children.
      12 patients followed for 1-12 years.
AB  - We reviewed 12 children, mean 5 (1-12) years, after corrective osteotomy of the
      ulna, combined with open reduction of the radial head for malunited anterior
      Monteggia lesions (Bado type I). A simple corrective osteotomy was used in the
      first 6 patients (group A) and a posterior angular osteotomy was used in the
      second group of 6 patients (group B). All osteotomies healed uneventfully, but 3
      patients had a persistent dislocation of the radial head. Children who had been
      treated with an angular osteotomy had the best clinical outcome).

PMID- 9524524
TI  - AO and Frykman's classifications of Colles' fracture. No prognostic value in 652
      patients evaluated after 5 years.
AB  - We retrospectively assessed hand and forearm symptoms of 652 patients with a
      Colles' fracture, 5 years after the fracture, using a questionnaire. The
      contralateral forearm, which was free of major injuries or illnesses, was used as
      control. Forearm and hand symptoms were common and only one quarter of the
      fractured forearms were completely free of symptoms at the time of review,
      whereas four fifths of the control forearms had no symptoms. Nearly half of the
      patients complained of impairment in various activities and 8% had had to give up
      leisure activities or make special arrangements at work. Demographic, and most of
      the fracture-related factors, were not associated with the symptoms. Neither AO
      nor Frykman's radiographic classifications of the primary fracture were of any
      use for predicting the clinical outcome.

PMID- 9524525
TI  - Self-administered outcome instrument in carpal tunnel syndrome. Reliability,
      validity and responsiveness evaluated in 102 patients.
AB  - We evaluated a Swedish version of a self-administered disease-specific outcome
      questionnaire for carpal tunnel syndrome regarding reliability, validity and
      responsiveness to clinical change. It consists of multi-item scales assessing
      symptom severity, function, patient satisfaction and quality of life. It was
      given to 102 patients before and 3 months after carpal tunnel release. Test
      retest reliability, studied in a subsample of 22 patients on two occasions with a
      1-3-week interval, showed good agreement between the scores. Internal consistency
      of the scales was high (Cronbach alpha 0.80-0.95). Validity of the scales was
      evaluated using the SF-36 general health questionnaire in a subgroup of 48
      patients as well as items concerning patient satisfaction, showing the expected
      relationships between these measures. Responsiveness of the scales to clinical
      change, estimated by the effect size and standardized response mean, was large
      (0.94-1.7). We conclude that this questionnaire can provide a standardized
      measure of symptom severity and functional status, as well as patient
      satisfaction and quality of life in the carpal tunnel syndrome.

PMID- 9524526
TI  - Hydatid disease of bones and joints. 8 cases followed for 4-16 years.
AB  - Hydatid disease is a rare parasitic disease that seldom involves the skeleton.
      Treatment is difficult because of problems with the preoperative diagnosis, the
      invasive nature of the bony involvement and the variable anaphylactic reaction to
      the cyst fluid antigen. We present 8 cases with osseous hydatidosis who were
      treated over a period of 11 years. The spine was involved in 2 cases, the ilium
      in 2, the hip in 2, the tibia in 1 and the humerus in 1. We point out that
      diagnosis is difficult and the prognosis is often poor.

PMID- 9524527
TI  - Comparison of cyclic compression, cyclic distraction and rigid fixation. Bone
      healing in rabbits.
AB  - A tibial osteotomy was created in rabbits and was fixed with an external fixator.
      The rabbits were divided into 3 groups in which cyclic distraction, cyclic
      compression and rigid fixation were applied. Fracture healing was similarly
      enhanced in the groups with cyclic compression and cyclic distraction. Axial
      cyclic movements seem to stimulate bone healing, regardless of the direction of
      the applied force.

PMID- 9524529
TI  - International Anesthesia Research Society 72nd clinical and scientific congress.
      Orlando, Florida, USA. March 7-11, 1998. Abstracts.

PMID- 9524528
TI  - Wear and osteolysis in total joint replacements.
AB  - This presentation summarizes the results of our recent studies on the
      pathogenesis of osteolysis around total joint arthroplasties. First, interface
      tissues with adjacent bone were retrieved and histopathologically investigated
      with reference to the cells on the bone surface. Secondly, polyethylene particles
      were extracted with the tissue digestion method and characterized with scanning
      electron microscopy. Finally, an animal model for osteolysis was created and
      various interface conditions were compared concerning their resistance to
      particle migration. Histopathological examinations demonstrated that active bone
      formation, regarded as a repair process, was the commonest feature, even in
      revised cases. They also highlighted the role played by macrophages, not as cells
      producing inflammatory mediators which could activate osteoclasts, but as cells
      primarily responsible for the bone loss in osteolytic lesions. Among the particle
      species present, only polyethylene particles were shown to play a significant
      role in macrophage recruitment and subsequent osteolysis. A quantitative
      extraction of polyethylene particles showed a significant difference in the
      "number" of particles between osteolysis positive and negative cases whereas the
      "sizes" of particles were similar in these two groups. The critical number of
      particles for osteolysis was around 1 x 10(10) particles/g tissue and the
      cellular reaction against phagocytosable particles accumulated over this
      concentration may be the prerequisite for progression of osteolysis. The animal
      model for osteolysis indicated that the progression of osteolysis depends on the
      integrity of the bone-implant interface. We suggest that the solid fixation of
      the prosthesis performed by current techniques (e.g., improved cementing
      technique, hydroxyapatite coating) is beneficial for preventing particle
      migration and subsequent osteolysis. CLINICAL RELEVANCE: Osteolysis induced by
      particulate wear debris from implant materials has been recognized as the major
      cause of long-term failure in total joint replacements. However, the development
      of preventive measures for this phenomenon has not been successful because the
      mechanism in which wear particles cause osteolysis is not quite clear. On the
      basis of results obtained in this study, we believe that the basic strategy for
      addressing the problem of osteolysis is to reduce the "number" of accumulated
      wear particles in the interface tissues. This could be achieved either by
      improving the materials or the geometry of the articulating counterface. Another
      possibility is to increase the integrity of the bone-implant interface to prevent
      particle migration. It is important to note that pre-clinical testing of
      materials and prosthetic designs should include an analysis of the
      characteristics of the particle generated (e.g., size and number). The widespread
      bone formation, even in revised cases, is encouraging in view of "conservative
      treatment" of aseptic loosening. Assuming that bone loss in aseptic loosening is
      not a remorseless process, some form of intervention, whether mechanical or
      pharmacological, might be possible to tip the balance more in favour of bone
      formation than resorption. A comprehensive understanding of the bone reactions in
      osteolysis, including the basic mechanisms of bone loss, shown in this study, are
      decisive for the development of preventive measures that may minimize the
      clinical impact of this phenomenon.

PMID- 9524530
TI  - 48th annual meeting of the Canadian Cardiovascular Society. Toronto Ontario,
      Canada, October 24-28, 1995. Abstracts.

PMID- 9524531
TI  - 99th annual meeting of the American Society for Clinical Pharmacology and
      Therapeutics. New Orleans, Louisiana, USA. March 30-April 1, 1998. Abstracts.

PMID- 9524532
TI  - Smoking cessation: information for specialists. Agency for Health Care Policy and
      Research.
AB  - This Quick Reference Guide for Smoking Cessation Specialists contains strategies
      and recommendations from Smoking Cessation Clinical Practice Guideline No. 18,
      designed to assist clinicians, smoking cessation specialists, and health care
      administrators/insurers/purchasers in identifying tobacco users and supporting
      and delivering effective smoking cessation interventions. These recommendations
      were made as a result of an exhaustive and systematic review and analysis of the
      scientific literature. The primary analytic technique used was meta-analysis.
      This Quick Reference Guide for Smoking Cessation Specialists highlights the
      recommendations for successful smoking cessation treatment: Every person who
      smokes should be offered smoking cessation treatment at every office visit.
      Clinicians should ask and record the tobacco-use status of every patient.
      Cessation treatments even as brief as 3 minutes a visit are effective. More
      intense treatment is more effective in producing long-term abstinence from
      tobacco. Nicotine replacement therapy (nicotine patches or gum), clinician
      delivered social support, and skills training are the three most effective
      components of smoking cessation treatment. Health care systems should make
      institutional changes that result in the systematic identification of, and
      intervention with, all tobacco users at every visit. Recommendations for smoking
      cessation specialists are: Assess the smoker who has entered an intervention
      program. Use a variety of clinical specialists. Ensure that the program is
      sufficiently intensive. Use a variety of program formats. Include effective
      counseling techniques. Target the smoker's motivation to quit. Provide relapse
      prevention intervention. Offer nicotine replacement therapy. Arrange follow up
      contact.

PMID- 9524533
TI  - [The treatment with levamisole of frequently recurring steroid-sensitive
      idiopathic nephrotic syndrome in children].
AB  - BACKGROUND AND OBJECTIVE: The treatment of frequently relapsing steroid-sensitive
      nephrotic syndrome in children with established immunosuppressive drugs
      (steroids, cyclophosphamide, cyclosporin A) sometimes presents problems because
      of the expected incidence of side effects. Stimulation of the immune system with
      the anthelminthic drug levamisole in this disease has been documented. Aim of
      this study was to assess in a prospective but uncontrolled series of observations
      its value and side effects. PATIENTS AND METHODS: 25 patients (15 boys, ten
      girls; median age 10 [3.5-22] years) were given levamisole, 2 mg/kg/48 h. Before
      this treatment was started eight of the children/adolescents (32%) had frequent
      relapses and 17 (68%) had become steroid-dependent. Treatment was started during
      steroid-induced remission and continued for 3-24 (median 6) month, while steroids
      were discontinued after four weeks. RESULTS: Relapse frequency per patient month
      was reduced from a mean of 0.5 (0.33-0.83) before to 0.31 (0-0.67) during
      levamisole administration (P < 0.001). In 12 patients (48%) no or considerably
      fewer relapses were observed. Patients with exclusively frequent relapses
      responded to levamisole better than those with steroid dependence (7/8 [87.5%]
      vs. 5/18 [27.7%], P = 0.01). Side effects were reversible leukopenia in two
      patients and nonspecific skin rash as well as epigastric pain in one patient.
      CONCLUSION: Levamisole is an efficacious addition or alternative, with a low
      incidence of side effects, in the treatment of frequently relapsing nephrotic
      syndrome, particularly so in yet steroid-dependent patients.

PMID- 9524534
TI  - [Aortic rupture after blunt chest trauma. Rapid diagnosis using transesophageal
      echocardiography when radiographic and computed tomographic findings are
      unclear].
AB  - HISTORY AND CLINICAL FINDINGS: A 37-year-old woman who was not wearing a seat
      belt while driving a car had a head-on collision at 70 km/h. On arrival of the
      emergency physician she was awake and responsive but complained of pain with
      bruising over the sternum and the epigastrium. Pressure on the sternum was
      painful. Arterial pressure was 95/60 mm Hg, heart rate 112/min. On admission the
      heart sounds were unremarkable and peripheral pulses normal. Vesicular sounds
      were heard over both lungs. In addition to multiple facial abrasions voluntary
      movements were impaired and the right knee-joint was swollen. INVESTIGATIONS: The
      ECG showed sinus tachycardia (103 beats/min) with left axis deviation, but was
      otherwise unremarkable. Initially the haemoglobin was 12.6 g/dl with normal white
      cell and platelet counts. Clotting tests, serum transaminases, creatine kinase,
      lactate dehydrogenase and other routine laboratory tests were within normal
      limits. TREATMENT AND COURSE: Because the haemoglobin level had fallen to 7.7
      g/dl within the first 4 hours erythrocytes concentrate was infused. The chest
      radiogram and subsequent computed tomography showed a mediastinal and paraaortic
      haematoma of unclear origin. Transoesophageal echocardiography (TEE) demonstrated
      rupture of the descending aorta with free floating intraluminal parts of the
      intima in the isthmal region, just distal to the origin of the left subclavian
      artery, which was not occluded. Colour Doppler echocardiography revealed abnormal
      flow into mediastinal and paraaortic tissues. At operation the echocardiographic
      findings were confirmed and part of the descending aorta was replaced by a 3 cm
      dacron tube during an aortic crossclamping time of 37 min. The patient was
      discharged after a postoperative stay of average length, during which her other
      injuries were treated. CONCLUSION: After blunt thoracic or deceleration trauma
      earliest possible TEE is indicated, because it can at once provide details of
      extent and degree of injury to heart and/or aorta.

PMID- 9524536
TI  - [Delayed vomiting after cytostatic chemotherapy].

PMID- 9524535
TI  - [Surgical treatment of acute pericardial tamponade in an infestation of the heart
      by Echinococcus].
AB  - HISTORY AND CLINICAL FINDINGS: A 56-year-old turkish patient, previously in good
      health, was admitted because of pain suggesting myocardial infarction. Physical
      examination of the heart, lungs and abdomen was unremarkable. INVESTIGATIONS AND
      DIAGNOSIS: The concentrations of myocardium-specific enzymes were not elevated
      and the ECG showed no signs of ischaemia. Echocardiography and magnetic resonance
      imaging ruled out acute aortic dissection, but demonstrated a round cystic space
      occupying mass over the anterior wall of the heart. Hydatid cyst was suspected
      from the imaging results and the patient's origin from area endemic for
      Echinococcus. The diagnosis was confirmed by a titre of 1:6,400 (normal: 1: <
      100) for Echinococcus antibodies. TREATMENT AND COURSE: Albendazole
      administration was initiated. Planned elective surgical removal of the hysatid
      cyst had to be performed urgently because of acute pericardial tamponade. Cyst
      rupture was suspected but an actually undamaged cyst was subtotally removed under
      cardiopulmonary bypass. The postoperative course was uneventful and albendazole
      treatment was continued. CONCLUSION: Because of the high incidence of fatal
      complications urgent surgical removal under cardiopulmonary bypass is the
      treatment of choice for hydatid cyst involving the heart. Perioperative
      albendazole administration is also essential.

PMID- 9524537
TI  - [Vascular endothelial growth factor VEGF stimulates angiogenesis in good and bad
      situations].

PMID- 9524538
TI  - [Approval of salaried company doctors for contract medical situations. Decision
      of the Federal Social Court on March 19, 1997].

PMID- 9524539
TI  - [Esophageal ulcer with heterotopy of the gastric mucosa and fistula].

PMID- 9524540
TI  - [Acetylsalicylic acid in ischemic insult].

PMID- 9524541
TI  - [Pathogenicity of oral rabies vaccine residues].

PMID- 9524542
TI  - Applying performance measurement to a nursing service.

PMID- 9524543
TI  - Colleagues in caring: the South Dakota experience.

PMID- 9524544
TI  - Harassment in the workplace.

PMID- 9524545
TI  - A career ladder based on Benner's model. An analysis of expected outcomes.

PMID- 9524546
TI  - Hospital employment of nursing personnel. Has there really been a decline?
AB  - There was a steady increase in the number of hours worked by nursing personnel in
      California hospitals from 1977 through 1996, mostly due to an increase in the
      number of hours worked by registered nurses (RNs). The hours worked by nursing
      personnel and RNs per case-mix adjusted discharge and per adjusted patient day
      also have increased. Possible explanations for the discrepancy between
      perceptions of declining nursing staffing and the data are discussed.

PMID- 9524547
TI  - An organization-wide approach for an effective communication system, Part 1.
AB  - This two-part series provides a cogent discussion of designing and implementing
      an effective communication system, with a committee structure based on the Joint
      Commission on Accreditation of Health Care Organizations (JCAHO) functions. Part
      one includes the development and design using a systems approach. Part two, which
      will be published in the April 1998 issue of JONA, will address the evaluation of
      outcomes and implications of this communication system. The experiential learning
      gained from this process is illustrated by the analysis of themes that surfaced
      during the implementation.

PMID- 9524548
TI  - Design and implementation of a patient classification system for rehabilitation
      nursing.
AB  - Development of a prototype patient classification (PCS) instrument designed
      specifically for rehabilitation patients is the focus of this article. The
      process of instrument development is discussed, as well as strategies used in
      implementing the PCS. These strategies include: staff education, management
      support, data collection, data analysis--including the development of supporting
      information systems, and ongoing use of the rehabilitation PCS. Changes
      engendered by implementation of the PCS also are discussed.

PMID- 9524549
TI  - Making consultation work.
AB  - In the current rapidly changing healthcare environment, nurse executives are
      likely to find themselves seeking and hiring consultants, as well as working with
      consultants who have been hired by others. Because working with a consultant
      entails a certain amount of risk and involves a commitment of both personal and
      organizational resources, nurse executives need to know how to be effective
      buyers and users of consultation services. The author presents guidelines for
      developing effective working relationships with consultants.

PMID- 9524550
TI  - Successful patient discharge. A comprehensive model of facilitators and barriers.
AB  - The need for effective discharge planning by nurses has become more urgent and
      complex in light of recent healthcare initiatives. In response to better
      understanding discharge planning, four focus groups were held to describe a
      comprehensive framework of factors needed for effective discharge that are
      relevant to multiple nursing specialties across practice sites. Through content
      analysis, four themes--common across sites and specialties--were identified as
      important to discharge.

PMID- 9524551
TI  - Improving certified nurse aide retention. A long-term care management challenge.
AB  - In the long-term care industry, the turnover rate among nurse aides is extremely
      high. This adversely affects resident satisfaction, resident care, morale, and
      finances. It presents a challenge to long-term care administration. Refusing to
      accept high turnover as an impossible situation allows changes to be made. The
      authors describe how the staff at one intermediate care facility identified its
      problems, assessed the causes, and implemented corrective action.

PMID- 9524552
TI  - An algorithm (decision tree) for the management of Parkinson's disease: treatment
      guidelines. American Academy of Neurology.

PMID- 9524554
TI  - 5-substituted analogues of 3-hydroxymethyl-5-aziridinyl-1-methyl-2-[1H-indole-4,7
      dione]prop-2-en- 1-ol (EO9, NSC 382459) and their regioisomers as hypoxia
      selective agents: structure-cytotoxicity in vitro.
AB  - A series of regioisomeric analogues of 3-hydroxymethyl-5-aziridinyl-1-methyl-2
      [1H-indole-4,7-dione]prop-2-en-1 -ol (EO9, NSC 382459) with the hydroxymethyl and
      hydroxypropenyl substituents situated at either the 2- or the 3-position of the
      indole ring were synthesized. The compound lacking the 2-hydroxypropenyl
      substituent (31) had similar properties to EO9 under both aerobic and hypoxic
      conditions against V79 cells and was more potent against a human tumour cell line
      (A549) than EO9. It was reduced by human DT-diaphorase (DTD) at more than double
      the rate of EO9, thus implicating the importance of the enzyme activation step.
      Compound 16 (lacking the 3-hydroxymethyl substituent) was a better substrate for
      human DTD than EO9, yet exhibited lesser toxicity under both aerobic and hypoxic
      conditions. The toxicity generated by 16 was attributed to the 5-aziridinyl
      moiety and suggests a greater contribution from the 3-substituent over the 2
      substituent. The toxicity of EO9 was attributed to a combination of the
      aziridinyl group and the leaving group properties of the 3-hydroxymethyl
      substituent. In general, compounds with a 5-methylaziridinyl moiety, such as EO8,
      exhibited substantially better hypoxia-selectivity due to much slower reduction
      by DTD (20-fold), thus reducing aerobic potency. All compounds had similar
      electron affinities, as indicated by their one-electron reduction potentials.

PMID- 9524553
TI  - Bis(dialkyl)dithiocarbamato cobalt(III) complexes of bidentate nitrogen mustards:
      synthesis, reduction chemistry and biological evaluation as hypoxia-selective
      cytotoxins.
AB  - Cobalt(III) complexes [Co(R2dtc)2(L)]+ containing two dithiocarbamate ligands (R
      = Me, Et, pyrrolidine) and a bidentate nitrogen mustard ligand (L) have been
      prepared as potential hypoxia-selective cytotoxins. The complexes were
      synthesized by treatment of the binuclear precursor [Co2(R2dtc)5]+ with the
      diamine mustards N,N'-bis(2-chloroethyl)ethylenediamine (BCE) and N,N-bis(2
      chloroethyl)ethylenediamine (DCE), or their non-alkylating analogues [N,N
      diethylethylenediamine (DEE) and N,N'-diethylethylenediamine (BEE)]. Cyclic
      voltammetry of the complexes in MeCN reveals quasi-reversible behaviour for the
      Co(III)/Co(II) couple, with E1/2 increasing in the order DCE < DEE approximately
      BCE < BEE. In MeCN/H2O electrochemical reduction is irreversible, indicating
      rapid substitution of H2O into the coordination sphere of the Co(II)
      intermediate. This fast ligand loss was confirmed by pulse radiolysis of
      [Co(Me2dtc)2(DEE)]+, while steady-state radiolysis showed that the initial
      intermediate disproportionates to [CoII(H2O)6]2+ + 2[CoII(Me2dtc)3]. The latter
      species reduces additional parent complex to give an overall stoichiometry of 3
      mol parent complex/mol reductant. [Co(Me2dtc)2(DCE)]+ decays rapidly by an
      analogous mechanism in hypoxic culture medium. This reaction is not inhibited by
      O2, indicating that reoxidation of the Co(II) intermediate by O2 is not rapid
      enough to compete with ligand dissociation. The resulting free R2dtc-ligands,
      rather than the released mustards, are primarily responsible for growth
      inhibition by [Co(R2dtc)2(L)]+ complexes, although DCE release does contribute to
      clonogenic cell killing. Clonogenic cell killing is not appreciably enhanced
      under hypoxic conditions for any of the dithiocarbamato complexes. This finding,
      coupled with their instability in culture medium, suggests that [Co(R2dtc)2(L)]+
      complexes are probably not suited for further development as bioreductive
      anticancer drugs.

PMID- 9524555
TI  - Antitumour polycyclic acridines. Part 2. Physicochemical studies on the
      interactions between DNA and novel polycyclic acridine derivatives.
AB  - The noncovalent interactions between a series of new polycyclic acridine
      derivatives (1-5) and salmon testes DNA have been studied using several
      physicochemical techniques. These include spectrophotometric analysis,
      fluorescence quenching, thermal denaturation, and circular and linear dichroism.
      In order to compare the extent of the DNA binding by compounds 1-5 in their
      neutral and cationic forms, all experiments have been conducted at pH 7.4 and at
      pH 5.0. Other polynucleotides, including [Poly(dA-dT)]2 and [Poly(dG-dC)]2, were
      used in order to study the DNA base-pair binding specificity of these novel
      annelated acridine derivatives. The results indicate that the new polycyclic
      acridines display the following properties: (i) they are strong DNA-binding
      ligands with affinities 10- to 400-fold greater than that of acridine, 3- to 100
      fold greater than that of m-AMSA (6) and 1- to 23-fold greater than that of
      proflavine at physiological pH (7.4); (ii) they have stronger DNA-binding
      activity at pH 5.0 as a result of the N-protonation of the aromatic chromophore;
      (iii) they bind more selectively to [Poly(dA-dT)]2 polynucleotide than to
      [Poly(dG-dC)]2 polynucleotide; (iv) within the series compound 3 binds to DNA
      less than compounds 1, 2, 4 and 5 at both pH values studied; and (v) the
      polycyclic acridines form a molecular complex with DNA undergoing intercalation
      inside the duplex macromolecule, as shown by linear and circular dichroism.
      Nevertheless, circular dichroism studies reveal alternative binding modes at low
      DNA: drug ratios.

PMID- 9524556
TI  - Synthesis, topoisomerase I inhibitory activity and in vitro cytotoxicity of
      camptothecin derivatives bearing five-membered heterocycle containing 10
      substituents.
AB  - A series of new camptothecin derivatives bearing certain five-membered
      heterocycles was synthesized and evaluated for in vitro cytotoxic activity. The
      cytotoxicity results show that camptothecin derivatives bearing pyrrole and
      thiophene rings were more potent than camptothecin, whereas those bearing furan
      were less active than camptothecin. Agarose gel electrophoresis shows different
      inhibitory activities of the camptothecin analogs towards topoisomerase I DNA
      cleavage. The pyrrole-containing compounds inhibit topoisomerase I DNA cleavage
      more strongly than camptothecin, but the thiophene and furan compounds do not
      show any inhibitory activities for DNA cleavage functions of topoisomerase I.
      Polyacrylamide gel sequencing electrophoresis shows that the pyrrole compounds
      induce single-strand breaks after incubating with a labeled DNA fragment. The
      results suggest that the pyrrole compounds fit the compound-enzyme-DNA complex
      better than camptothecin and the other analogs.

PMID- 9524557
TI  - Germ cell cancer and disorders of spermatogenesis: an environmental connection?
AB  - Why is there a small peak of germ cell tumours in the postnatal period and a
      major peak in young age, starting at puberty? And, paradoxically, small risk in
      old age, although spermatogenesis is a lifelong process? Why is this type of
      cancer more common in individuals with maldeveloped gonads, including undescended
      testis, gonadal dysgenesis and androgen insensitivity syndrome? Why has there,
      during the past 50 years, been a quite dramatic increase in testicular cancer in
      many developed countries? These are just a few of many questions concerning
      testicular cancer. However, the recent progress in research in the early stages
      of testicular cancer (carcinoma in situ testis (CIS)) allows us to begin to
      answer some of these questions. There is more and more evidence that the CIS cell
      is a gonocyte with stem cell potential, which explains why an adult man can
      develop a non-seminoma, which is a neoplastic caricature of embryonic growth. We
      consider the possibility that CIS cells may loose their stem cell potential with
      ageing. Along these lines, a seminoma is regarded a gonocytoma where the single
      gonocytes have little or no stem cell potential. The Sertoli and Leydig cells,
      which are activated postnatally and during and after puberty, may play a crucial
      role for both the development of the CIS gonocyte and progression of the neoplasm
      to invasiveness. The reported increase in testicular cancer is not the only sign
      that male reproductive health is at risk. There are reports that undescended
      testis and hypospadias have become more common. Also semen quality has
      deteriorated, at least in some countries. The epidemiological evidence suggests
      that environmental factors may play a role. Are the environmental hormone
      disrupters (e.g. DDT, PCB, nonylphenol, bisphenol A) to be blamed for the
      apparently synchronised deterioration in these aspects of male reproductive
      health?

PMID- 9524558
TI  - The value of the biopsy of the contralateral testis in patients with testicular
      germ cell cancer: the recent German experience.
AB  - PURPOSE: Testicular intraepithelial neoplasia (TIN; so-called carcinoma in situ
      of the testis), the precursor of testicular germ cell neoplasms can be detected
      by testicular biopsy many years before the clinical manifestation of the tumour.
      This study looked at the prevalence of contralateral TIN in patients with
      testicular germ cell cancer. The purpose was to evaluate this new approach of
      early detection of testicular cancer and to evaluate the current management
      strategies. PATIENTS, METHODS: 1954 consecutive patients with unilateral
      testicular germ cell tumour underwent contralateral biopsy. All specimens were
      examined immunohistologically with staining for placental alkaline phosphatase.
      Patients with TIN were usually submitted to low-dose radiotherapy of the testis.
      A rebiopsy was performed after 3 months. Endocrinological evaluations were done
      before, during and after treatment. RESULTS: TIN was observed in 4.9% (95%
      confidence intervals 3.95%-5.91%). Testicular atrophy constitutes a 4.3 fold
      increased risk of having contralateral TIN. 64% of the cases with TIN were found
      in clinically normal testes. Patients with TIN were significantly younger than
      those without (p < 0.017). No case with TIN was found in patients older than 50
      years. Three patients developed a second testicular tumour during follow-up
      despite a negative biopsy. After radiotherapy, all of 23 patients had complete
      disappearance of TIN in the rebiopsy. After chemotherapy, 3 of 10 patients had
      persistent TIN histologically. After radiotherapy, 12 of 41 patients required
      testosterone replacement. CONCLUSION: The prevalence of contralateral TIN accords
      well with the known prevalence of bilateral testicular tumours. Testicular
      atrophy is a strong indicator for the presence of TIN but about 60% of TIN-cases
      occur without atrophy. Local radiotherapy to the testis with 18-20 Gy is
      efficaceous in eradicating TIN, but it causes significant damage to almost one
      quarter of these patients. Chemotherapy is an unsafe treatment for TIN. This
      study shows the feasibility of early detection of testicular cancer in a high
      risk population by means of searching for TIN. Although the management of the
      condition still needs refinement, the TIN-concept offers an avenue for the early
      detection of testicular cancer and early conservative management.

PMID- 9524559
TI  - Gonadal function in men with testicular cancer: biological and clinical aspects.
AB  - This paper reviews current knowledge about the effect of testicular germ cell
      cancer (TGCC) on gonadal function and of cancer treatment on spermatogenesis and
      Leydig cell function. It is well documented that testicular cancer is associated
      with impaired spermatogenic function and some patients already have impairment of
      Leydig cell function before orchidectomy. The degree of spermatogenic dysfunction
      is higher than what can be explained by local tumour effect and by a general
      cancer effect, since patients with other malignant diseases have normal, or only
      slightly decreased, semen quality. Furthermore, sperm counts after orchidectomy
      are further reduced to less than half of the values in healthy men, even in
      patients cured from the cancer disease after orchidectomy alone. These
      observations are supported by histological investigations which have shown a high
      prevalence of abnormalities of spermatogenesis in the contralateral testis in
      patients with unilateral TGCC. The association between testicular cancer and poor
      gonadal function is very interesting both from a biological and from a
      therapeutic point of view. Firstly, the increase in incidence of testicular
      cancer has been suggested to be associated with a general decline in male
      reproductive health and it seems likely that the development of TGCC shares
      common aetiologic factors with development of other types of testicular
      dysfunction. This suggestion is supported by the observation that men with
      various types of gonadal dysfunction such as testicular dysgenesis, androgen
      insensitivity syndrome, and cryptorchidism have increased risk of testicular
      cancer. Secondly, the general cure rate in patients with testicular cancer
      exceeds 90% and the quality of life, including fertility aspects, is therefore
      important in the management of these patients. Spermatogenesis is already so
      severely impaired before treatment that fertility is lower than in healthy men.
      Moreover, radiotherapy and chemotherapy both induce dose-dependent impairment of
      spermatogenesis and recovery of spermatogenesis after treatment may be long
      lasting even more than five years in some patients. Sufficient androgen
      production is seen in the majority of the patients, but some patients suffer from
      testosterone deficiency. The effect of chemotherapy on Leydig cell function also
      seems to be dose-dependent. In conclusion there is no doubt that testicular
      cancer is associated with poor gonadal function even before treatment.
      Furthermore, the treatment of testicular cancer may have a serious impact on the
      gonadal function in these patients, most of whom are in the reproductive age.
      Moreover, the epidemiological and clinical data indicate a common aetiology
      between testicular germ cell cancer and other abnormalities in male reproductive
      health (such as infertility and cryptorchidism). These observations are in
      agreement with the suggestions of hormonal involvement in the aetiology of
      testicular cancer. Generally, men with TGCC need counselling about their
      reproductive function with respect to semen cryopreservation, chance of recovery
      of spermatogenesis, fertility, and the possible need for androgen replacement.

PMID- 9524560
TI  - Hormonal stimulation of the recovery of spermatogenesis following chemo- or
      radiotherapy. Review article.
AB  - Radiation and chemotherapeutic drugs produce prolonged depression of sperm counts
      in rodents and humans. Previously, three approaches have been developed in
      experimental animals that have had some success in preventing or reversing this
      toxicity. These approaches included pretreatment with hormones that suppress
      spermatogenesis, stimulation of stem cell number, and supplementation with
      testosterone. A different rationale for the ability of particular hormonal
      treatments to reverse prolonged azoospermia is presented in this review. In many
      cases prolonged azoospermia occurs even though the stem spermatogonia survive the
      toxic insult, but the differentiation of these spermatogonia to produce sperm
      fails. In the rat, the block appears to be at the differentiation of the A
      spermatogonia. Hormone treatments with testosterone or with GnRH agonists, which
      suppress intratesticular testosterone levels, relieve this block and result in
      the production of differentiating cells. When the hormone treatment is stopped
      the production of differentiating cells continues, mature sperm are produced, and
      fertility is restored. If a similar mechanism can be demonstrated to hold in
      humans, the fertility of men who have been rendered infertile by treatments for
      testicular and other cancers could be improved.

PMID- 9524561
TI  - Spermatogonial transplantation and reconstitution of donor cell spermatogenesis
      in recipient mice.
AB  - Recently, we described a method to transplant testicular cells from a fertile
      donor mouse to the seminiferous tubules of an infertile recipient male, where the
      donor cells generate spermatogenesis. Spermatozoa produced by the transplanted
      cells in the recipient testis will fertilize eggs and transmit the donor
      haplotype to the resulting animals. In the most successful transplantations, up
      to 80 per cent of progeny sired by the recipient male arise from donor cell
      derived spermatozoa. The cell responsible for generation of spermatogenesis
      following transplantation clearly is a spermatogonial stem cell, since the
      repopulation of recipient testes extends for periods exceeding 12 months. In the
      past year, experiments have shown that rat testicular cells transplanted to the
      seminiferous tubules of immunodeficient mice will generate rat spermatogenesis
      and produce normal appearing rat spermatozoa, opening the possibility of
      xenogeneic testicular cell transplantation for other species. In addition, it has
      proved possible to cryopreserve spermatogonial stem cells for long periods,
      following which they will produce normal spermatogenesis when transplanted to a
      recipient. The ability to cryopreserve testicular stem cells makes individual
      male germ lines immortal. In current work, we are focusing on techniques to
      increase the efficiency of spermatogonial transplantation and methods to culture
      the stem cells.

PMID- 9524562
TI  - Different fate of primordial germ cells and gonocytes following transplantation.
AB  - We have previously demonstrated that both donor primordial germ cells (PGCs) and
      gonocytes are capable of establishing spermatogenesis in the lumen of the
      seminiferous tubules of an adult host following transplantation in rats. Here we
      show that the PGCs, either in crude suspensions or after purification, undergo
      spermatogenesis only in the intraluminal compartment of the host's seminiferous
      tubules, while 4-5 days postpartum gonocytes also interdigitate with the host's
      seminiferous epithelium. The donor seminiferous epithelium was always in
      synchrony with the cycles of the host's spermatogenesis. It seems that the
      pattern of spermatogenesis of donor germ cells following transplantation in terms
      of its spacial location and the connection with the host's seminiferous
      epithelium depends on their developmental stages at transfer.

PMID- 9524563
TI  - Candidate regions for testicular cancer susceptibility genes. The International
      Testicular Cancer Linkage Consortium.
AB  - Although the aetiology of testicular cancer is unknown, a clear familial
      component has been identified in a number of studies. In an effort to identify
      susceptibility genes for testicular cancer, the International Testis Cancer
      Linkage Consortium has been collecting families with multiple cases of testicular
      cancer. These families have been genotyped for a set of markers across the genome
      in two separate studies. The family information has also been pooled across the
      two studies so that the combined evidence can be assessed. While no genomic
      region gives overwhelming support for a testicular cancer predisposition gene,
      several regions, notably on chromosomes 3, 5, 12 and 18 show suggestive evidence
      worthy of further examination. The Consortium is now attempting to identify
      further families in an attempt to confirm or deny these leads.

PMID- 9524564
TI  - Towards the isolation of a human malignant extragonadal germ cell tumour
      associated breakpoint in chromosome 11q13.
AB  - In a previous study we have defined a subgroup of human malignant extragonadal
      germ cell tumours that is characterized by complex translocations involving
      chromosomes 6 and 11 (Echten et al. 1995). Here we report (i) the use of
      fluorescent in situ hybridization, pulsed field gel electrophoresis and direct
      visual hybridization techniques to localize the tumour-associated breakpoint
      within band 11q13, and (ii) the construction of a phage library enriched for this
      region to facilitate genomic walks towards the breakpoint. Extensive breakpoint
      flanking contigs were generated and within these contigs six candidate genes
      could be identified.

PMID- 9524566
TI  - P53 tumour suppressor gene and germ cell neoplasia.
AB  - P53 tumour suppressor gene mutations occur in approximately 50% of common solid
      tumours such as breast, colon and lung. In contrast, p53 gene mutations occur
      infrequently (< 3%) in germ cell tumours, even though p53 protein is expressed at
      high levels in the vast majority of tumour samples. P53-regulated genes are not
      correspondingly over-expressed in germ cell tumour samples and cell lines,
      indicating that p53 functions poorly as a transcription factor in this tumour
      type. High levels of wild-type p53 may contribute, in part, to the
      chemosensitivity of germ cell tumours.

PMID- 9524565
TI  - The cytogenetic theory of the pathogenesis of human adult male germ cell tumors.
      Review article.
AB  - Human male germ cell tumors (GCTs) represent a biological paradox because, in
      order to develop into a pluripotential tumor, a germ cell destined to a path of
      limited or no proliferation must acquire the potential for unlimited
      proliferation. In addition, it must acquire the ability to elicit embryonal
      differentiation patterns without the reciprocal inputs from fertilization and the
      imprinting-associated genomic changes which are a part of normal embryonal
      development. Although much speculated about, the genetic mechanisms underlying
      these properties of male GCTs remain enigmatic. Recent cytogenetic and molecular
      genetic analyses of these tumors are providing new insights and new testable
      hypotheses. Based on our recent work, we propose two such hypotheses. One relates
      to the mechanism of germ cell transformation and germ cell tumor development. We
      suggest that the invariable 12p amplification noted as early as in carcinoma in
      situ/intratubular germ cell neoplasia (CIS/ITGCN) lesions leads to deregulated
      overexpression of cyclin D2, a cell cycle G1/S checkpoint regulator with
      oncogeneic potential. Such overexpression reinitiates the cell cycle. We
      visualize this happening during the pachytene stage of meiosis through aberrant
      recombinational events which lead to 12p amplification. The other hypothesis
      relates to the origin of primary extragonadal GCTs. By comparing cytogenetic
      changes in primary mediastinal versus gonadal lesions, we propose that, in
      contrast to long-standing speculation that primary extra-gonadal tumors arise
      from embryonally misplaced primordial germ cells, these lesions arise from
      migration of transformed gonadal germ cells.

PMID- 9524567
TI  - Immunohistochemical and mutational analysis of the p53 tumour suppressor gene and
      the bcl-2 oncogene in primary testicular germ cell tumours.
AB  - The role of p53 in testicular germ cell tumours is still contradictory based on
      the finding of immunohistochemical overexpression at the protein level, but lack
      of mutations at the DNA level. In addition, p53 wild-type activity has been
      demonstrated in cell culture experiments. Overexpression of the proto-oncogene
      bcl-2 might block p53-induced apoptosis and might inhibit p53 functional
      activity. To clarify the apparent paradox with respect to p53 overexpression and
      lack of mutations, an immunohistochemical and mutational analysis of p53 and bcl
      2 in TGCT was performed. Ten normal testes, 52 CIS and 151 clinical stage I
      nonseminomatous GCTs were included in our study. A commercially available anti
      p53 polyclonal rabbit antibody and an anti-bcl-2-mouse monoclonal antibody were
      used to stain the 5pm sections. Staining was assessed by counting at least 500
      cells from the area of the most intense staining in each tumour cell type, and
      this was scored semiquantitatively for intensity of staining on a 4 point scale.
      In addition, 30 primary GCTs were included in the mutational analysis: areas with
      p53 overexpression were identified and microdissected prior to DNA extraction.
      p53 exons 5-8 were amplified by polymerase chain reaction (PCR) followed by
      single strand conformation polymorphism analysis. Templates demonstrating band
      shifts on SSCP were subjected to direct DNA sequence analysis. None of the normal
      testes, 32/52 (62%) CIS, and 142/151 (94%) germ cell tumours exhibited p53
      overexpression. p53 expression was significantly lower in mature teratomas (0.8
      +/- 0.2) than in other germ cell tumour components (2.8 +/- 1.2, p > 0.001). PCR
      SSCP did not reveal any missense mutations or deletions for the p53 gene. Bcl-2
      protein expression was observed in none of the normal testes, in none of the CIS,
      and in 14/151 (9.3%) germ cell tumours. 13/14 germ cell tumours demonstrated bcl
      2 expression only in the glandular and stromal elements of their teratomatous
      components whereas all other components were negative for bcl-2. Our results--p53
      overexpression, lack of p53 mutations, undetectable bcl-2--are consistent with
      recent in vitro studies. High susceptibility of testicular cancer to drug-induced
      apoptosis appears to be the result of wild-type p53 and lack of bcl-2. Radiation
      and chemotherapeutic insensitivity of mature teratomas might be the result of bcl
      2 overexpression and lack of p53 overexpression. Therefore, chemoresistance to
      DNA damaging agents might be reflected by the expression of p53 and bcl-2 and it
      might be useful to evaluate p53 and bcl-2 in primary tumours and metastatic
      lesions in order to identify patients early with primary or secondary
      chemoresistance.

PMID- 9524568
TI  - Inhibin gene expression in a large cell calcifying Sertoli cell tumour and serum
      inhibin and activin levels.
AB  - Inhibin is a potential tumour suppressor gene product in the gonads. While
      inhibin gene products may have a role in tumourigenesis, serum inhibin levels can
      be used as a marker for ovarian tumours derived from granulosa cells. Tumours
      derived from Sertoli cells, testicular counterparts of granulosa cells, are rare.
      To assess whether inhibin could be used as a human Sertoli cell tumour marker,
      serum inhibin and activin levels and inhibin subunit mRNA expression in the
      testis were studied. Northern blot and in situ hybridization revealed abundant
      expression of inhibin alpha, beta A, and beta B subunit mRNAs in large cell
      calcifying Sertoli cell tumours found in a 12-year old boy with Carney complex.
      The tumours were multifocal and bilateral. Serum inhibin levels were clearly
      elevated at the time of the diagnosis, decreased by 50% after one of the testes
      was removed, and were low or undetectable after the second orchidectomy six weeks
      later. Activin was undetectable before the orchidectomies, while a low
      concentration of activin-A was measured after them. Follicle stimulating hormone
      (FSH) concentration increased from normal pubertal value to castration level as
      expected. Normal seminiferous tubules also showed inhibin subunit alpha and beta
      B mRNA expression, whereas inhibin beta A mRNA was expressed in normal Leydig
      cells. These data suggest that serum inhibin reflects Sertoli cell activity and
      can be used as a human tumour marker.

PMID- 9524569
TI  - Oct-4: more than just a POUerful marker of the mammalian germline?
AB  - Mammals lack visible cytoplasmic components in the oocyte that could account for
      'germline determinants' as identified in various non-mammalian species. Actually,
      mammals might not define the germline autonomously by localized 'germline
      determinants' but conditionally depending on the position of cells within the
      embryo. The Oct-4 gene encodes a transcription factor that is specifically
      expressed in the toti- and pluripotential stem cells of the mouse embryo and so
      far has only been found in mammalian species. Oct-4-expressing embryonal cell
      retain the capacity to differentiate along multiple lineages and they have been
      suggested to be part of a 'totipotent germline cycle' that links one generation
      to the next.

PMID- 9524570
TI  - Early stages in male germ cell differentiation in the mouse. Review article.
AB  - Primordial germ cells arise during gastrulation and migrate from the hindgut into
      the gonad primordium during early organogenesis. In this article, we discuss
      factors that control migration, proliferation and targeting of the PGCs. In
      particular we discuss how changes in adhesiveness control germ cell positioning
      in the gonad, and the molecules involved.

PMID- 9524571
TI  - Primordial germ cells, stem cells and testicular cancer.
AB  - Primordial Germ Cells (PGCs) arise in the mouse embryo as a small population of
      cells some way from the gonad anlagen. In order for the embryo to develop into a
      fully fertile adult animal the PGCs must increase in number and reach the gonad.
      Mutations causing sterility in the mouse have identified some of the genes
      involved in regulating PGC development and some of these genes have been
      molecularly cloned. Similarly, mutations affecting the development and
      differentiation of PGC-derived tumors (teratomas and teratocarcinomas) have been
      identified in certain strains of mice and these identify genes involved in the
      normal growth and differentiation of PGCs. These studies should help to define
      the role of growth factors in PGC development and in the development of germ-cell
      derived tumors.

PMID- 9524572
TI  - Regulation of germ cell death in mammalian gonads.
AB  - A large number of primordial germ cells (PGCs), as well as spermatogonia, undergo
      programmed cell death or apoptosis in the physiological context. In this process,
      environmental, cytoplasmic and nuclear factors are involved. Bcl-2 and its
      related molecules are known as general regulators of cell death, and some are
      important for survival of PGCs and spermatogonia. Steel factor, a ligand for c
      Kit, also supports growth and survival of these cells. In addition, bone
      morphogenetic protein (BMP)8B and Desert Hedgehog (Dhh), which are secreted
      proteins, and a nuclear factor, c-Myc, play a role in spermatocyte survival. This
      suggests that germ cell survival or death at each stage of differentiation is
      precisely controlled by specific signalling pathways which consist of a number of
      molecules.

PMID- 9524573
TI  - Neural differentiation of rhesus embryonic stem cells.
AB  - Primate embryonic stem (ES) cells are capable of indefinite, undifferentiated
      proliferation and maintain the potential to differentiate to trophoblast and
      derivatives of embryonic endoderm, mesoderm, and ectoderm. We previously reported
      that neural differentiation by rhesus ES cells in teratomas includes tissue with
      a remarkable resemblance to neural tube (Thomson et al. 1995). Here we examine a
      series of markers including a cell proliferation marker, neurofilament proteins,
      and glial fibrillary acidic protein (GFAP) in teratomas at 5, 6, 7, 9, and 12
      weeks after rhesus ES cell transplantation into muscles of immunodeficient mice.
      All teratomas examined contained derivatives of all three embryonic germ layers.
      Neural differentiation included tissues resembling neural tube and embryonic
      ganglia, as well as individual dispersed neurons, and brain-like gray matter.
      Tumours of all ages contained neurons and proliferating cells, indicated by
      staining for neurofilament subunits and Ki67 antigens. Younger tumours contained
      no or few astrocytes indicated by the absence of GFAP staining, but as these
      tumours developed, there was an increase in astrocyte differentiation. The
      results indicate that normal neural differentiation is recapitulated, in part, by
      the differentiation of rhesus ES cells in teratomas. The differentiation of
      rhesus ES cells provides an important new model for understanding human neural
      differentiation.

PMID- 9524574
TI  - Teratocarcinomas and human embryology: pluripotent human EC cell lines. Review
      article.
AB  - The histogenesis of germ cell tumours (GCT) reflects the normal processes of
      gametogenesis, fertilisation and subsequent embryonic cell differentiation.
      Understanding the mechanisms that control the differentiation of embryonal
      carcinoma (EC) cells into a variety of embryonic and extraembryonic cell types is
      pertinent to understanding the progression of GCT. EC cells also provide a tool
      for analysing the mechanisms that control differentiation during embryonic
      development, and particularly the mechanisms that control differentiation along
      alternative cell line, NTERA2, into neurones and other cell types in response to
      agents such as retinoic acid, HMBA and the bone morphogenetic proteins. We have
      also compared the pluripotent NTERA2 EC cells with other human EC cell lines that
      exhibit a much reduced capacity for cell differentiation. A variety of genes are
      activated during NTERA2 differentiation. In particular we have identified a novel
      human member of the wnt family. This wnt gene is activated following retinoic
      acid induction of differentiation but is later down-regulated as the cells mature
      into neurones and other cell types. We have also observed expression of genes
      belonging to the Frizzled family, which is likely to include genes encoding
      receptors for the wnt gene products. Thus in the NTERA2 system, genes pertinent
      to regulating cell differentiation during embryonic development are activated and
      appear to play a role in modulating how these pluripotent human EC cells
      differentiate.

PMID- 9524575
TI  - CD30 and its ligand: possible role in regulation of teratoma stem cells.
AB  - Like the oocyte, the cells of the early embryo, and primordial germ cells, human
      teratocarcinoma stem cells are pluripotent, capable of giving rise to a wide
      range of somatic and extraembryonic tissues. Growth factors which regulate the
      growth of multipotent stem cells in the mouse have been identified, but none of
      these have been shown conclusively to have similar effects on human or primate
      multipotent stem cells. CD30 is a member of the tumour necrosis factor receptor
      superfamily with a restricted pattern of tissue distribution, limited to immune
      cells, decidual tissue, and human embryonal carcinoma: in common with other
      embryonal carcinoma markers, CD30 is found in foci of cells in a sub-population
      of seminomas. CD30 ligand is a transmembrane protein, structurally related to
      tumour necrosis superfamily members TNF alpha, TNF beta, and CD40. CD30 ligand is
      expressed by T and B lymphocytes, macrophages, and a variety of normal
      haematopoietic cells and tumours derived from them, and exerts pleiotropic
      effects on normal and malignant lymphoid cells, including death, differentiation,
      or cell division. Studies on cultured cell lines derived from human embryonal
      carcinomas and yolk sac carcinomas confirm CD30 expression in the former but not
      the latter, and show that CD30 expression is down-regulated during stem cell
      differentiation in vitro. Transcripts for CD30 ligand are found at highest levels
      in yolk sac carcinoma cell lines, but are also found in embryonal carcinoma. CD30
      ligand protein is detected in yolk sac carcinoma and nullipotent embryonal
      carcinoma cell lines. Exogenous CD30 ligand has no effect on multipotent human
      stem cell growth in vitro. However, the receptor-ligand pair may function in
      autocrine regulation of embryonal carcinoma stem cells. CD30 and its ligand are
      candidate stem cell identity factors, juxtacrine regulators whose sole function
      is to identify a cell's position in a developmental hierarchy.

PMID- 9524577
TI  - Carcinoma in situ and seminoma in equine testis.
AB  - The presence of atypical germ cells resembling carcinoma in situ of human testis
      is reported for the first time in an unilaterally cryptorchid stallion. These
      cells were found in association with developing intratubular seminoma indicating
      they represented carcinoma in situ.

PMID- 9524576
TI  - Testicular teratocarcinogenesis in mice--a review.
AB  - Spontaneous testicular germ cell tumours in humans and mice are remarkable for
      their diverse composition. These tumours are usually composed of an extraordinary
      variety of cell and tissue types including muscle, skin, bone, cartilage, and
      neuroepithelia. Their diverse composition reflects their origin from totipotent
      primordial germ cells at about Day 12 of fetal development. Although much is
      known about the development of these tumours, remarkably little is known about
      the genetics of the mammalian primordial germ cell lineage or about the genes
      that control susceptibility to spontaneous testicular germ cell tumours in humans
      or mice. Conventional genetic analysis of susceptible 129/Sv mice is difficult
      because of the large number of susceptibility genes and their low penetrance. We
      are taking advantage of the Ter mutation to simplify the genetic analysis.
      Various evidence suggests that Ter is neither necessary nor sufficient for
      tumourigenesis. Instead, Ter acts as a modifier, dramatically increasing tumour
      incidence from approximately 1% in +/+ males, to approximately 17% in Ter/+ males
      and approximately 94% in Ter/Ter males. Segregation analysis suggests that Ter
      increases tumour incidence by requiring some, but perhaps not all, of the 129/Sv
      derived susceptibility genes. With standard crosses that segregate for the Ter
      mutation, identification not only of Ter but also of these 129/Sv-derived
      susceptibility genes should be possible. In this paper, we review the genetics
      and development of germ cell tumours in 129/Sv mice, summarize the status of Ter
      mapping, and provide evidence that different genetic pathways lead to unilateral
      and bilateral tumours.

PMID- 9524578
TI  - Genomic imprinting in testicular germ cell tumours.
AB  - Genomic imprinting refers to the parental origin-specific functional difference
      between the paternally and maternally-derived mammalian haploid genome. Normal
      embryogenesis depends on the presence of both a paternal and a maternal copy of
      particular chromosomal regions, containing the so-called imprinted genes. Genomic
      imprinting is established somewhere in the maturation from a primordial germ cell
      to a mature gamete, either spermatid or oocyte. We discuss the value of
      testicular cancers, especially those derived from the germ cell lineage, as a
      model to study erasement of the biparental pattern of genomic imprinting as
      present in the zygote and establishment of the paternal pattern during
      spermatogenesis. In addition, we will present data on the presence of X
      inactivation in these cancers.

PMID- 9524579
TI  - Developmental arrest of germ cells in the pathogenesis of germ cell neoplasia.
AB  - Clinical observations and epidemiological evidence suggest that important
      aetiopathological events that cause neoplastic transformation of the male germ
      cell may occur in fetal life or early infancy. The incidence of germ cell
      neoplasia is high in individuals with various disorders of gonadal development
      and sexual differentiation, such as gonadal dysgenesis or androgen insensitivity
      syndrome. Increased risk has also been noted in individuals with trisomy 21,
      idiopathic infertility and low birth weight. Infertility is sometimes associated
      with small aberrations of sex chromosomes (e.g. low frequency mosaicism XY/XO)
      which can also be found in patients with testicular cancer. The variety of
      conditions that predispose to testicular neoplasia and the rise in its incidence
      in many countries speaks for the influence of environmental factors which may
      affect genetically predisposed individuals. We hypothesise that if the
      development of the testis is disturbed or delayed, primordial germ cells or
      gonocytes undergo maturation delay or differentiation arrest which may render
      them susceptible to neoplastic transformation. Morphologically homogenous
      premalignant carcinoma in situ (CIS) cells have the potential to differentiate
      into a variety of histological forms of overt testicular tumours. Analysis of
      cell surface antigens expressed by CIS cells found in the vicinity of pure and
      mixed tumours demonstrates that CIS cells are phenotypically heterogeneous.
      Comparison of the phenotypes of CIS cells, primordial germ cells, human embryonal
      carcinoma cells and closely related primate embryonal stem cells reveals various
      similarities but also differences. We speculate that phenotypical heterogeneity
      of CIS cells may be associated with their potential to give rise to different
      tumour types, and may be related to the developmental stage of the early germ
      cell which has undergone malignant transformation.

PMID- 9524581
TI  - Human endogenous retrovirus (HERV)-K transcripts in germ cell and trophoblastic
      tumours.
AB  - Prompted by the observation of retroviral particle formation in teratocarcinoma
      cell lines and the consistent finding of antibodies against Gag and Env proteins
      encoded by human endogenous retrovirus (HERV)-K genomes in the sera of patients
      with classical seminoma, we studied ovarian and testicular germ cell tumours,
      their precursor lesions, dysgenetic gonads, and trophoblast lesions for
      expression of HERV-K sequences by in situ hybridization using radioactive and non
      radioactive probes. HERV-K transcripts were detected in all testicular and
      ovarian germ cell tumours with the exception of teratomas and spermatocytic
      seminomas. HERV-K expression was also common to testicular carcinoma in situ as
      well as gonocytes of dysgenetic gonads. Among gestational trophoblastic lesions,
      HERV-K expression was regularly found in choriocarcinomas, but not in molar
      lesions. The patterns of HERV-K expression suggest a common molecular
      pathogenesis of most germ cell tumour entities and malignant gestational
      trophoblastic disease. They furthermore support the concept of carcinoma in situ
      as a precursor lesion common to most testicular germ cell neoplasms. The
      detection of HERV-K gene products in body fluids and tissues may aid diagnosis
      and monitoring of germ cell tumours and related lesions.

PMID- 9524580
TI  - The platelet-derived growth factor alpha-receptor 1.5 kb transcript: target for
      molecular detection of testicular germ cell tumours of adolescents and adults.
AB  - An accurate and relatively simple method to detect testicular germ cell tumours
      of adolescents and adults (TGCTs) could be useful for early detection and may
      help to avoid unnecessary orchidectomies. We report a highly sensitive reverse
      transcription polymerase chain reaction assay for the 1.5 kb transcript of the
      platelet-derived growth factor-alpha receptor for molecular diagnosis of TGCTs.
      As a simulation of the clinical application of the assay the approach was applied
      on through-cut-biopsies from orchidectomy specimens. In a series of 31 specimens,
      the 1.5 kb transcript was detected in all samples containing either carcinoma in
      situ, or an invasive TGCT, with mature teratoma as only exception. No expression
      was detected in normal parenchyma. On the basis of the through-cut-biopsies the
      assay shows a sensitivity of 0.87 and a specificity of 1.00. The positive and
      negative predictive values of the test are 1.00 and 1.00. For carcinoma in situ
      alone these values are 0.86, 1.00, 1.00, and 0.80, respectively. The figures at
      least equal the results obtained with the most sensitive morphological/enzyme
      histochemical study of duplicate biopsies. We conclude that the 1.5 kb transcript
      of the platelet-derived growth factor-alpha receptor is a useful molecular marker
      for TGCTs, and therefore of interest in a clinical setting.

PMID- 9524582
TI  - The origin and biology of CIS cells: general discussion.
AB  - Participants at the 4th Copenhagen Workshop on Carcinoma in situ and Cancer of
      the Testis, representing cell biologists and tumour biologists, met together to
      discuss the similarities and differences between primordial germ cells (PGCs) of
      the embryo, and the carcinoma in situ (CIS) stem cell of human testicular germ
      cell tumours (GCTs). Much has been discovered about PGCs in the last 10 years and
      we still do not know the exact nature of CIS cells. Knowledge of PGCs comes
      mainly from mouse experiments and knowledge of CIS comes from the study of human
      tumours. A mouse model of human GCT would help to investigate the nature of CIS
      cells. Grafting mouse male genital ridges into mouse fetal testes results in the
      development of testicular tissue and the formation of teratomatous tumour
      components. Amplification of PGCs in culture is possible but this results in
      their transformation into embryonic germ (EG) cells. CIS cells die by apoptosis
      if they are isolated, and short-term culture is only possible if the CIS cells
      are cultured in their normal environment within seminiferous tubules. It may be
      possible for CIS cells to differentiate in culture although they cannot be
      maintained in culture as isolated cells. Human CIS cells are likely to be formed
      as a result of in utero factors rather than agents acting on normal adult
      testicular germ cells. EG cells stimulate feeder cells by paracrine factors but
      it is not known if these cells produce autocrine factors.

PMID- 9524583
TI  - Increasing incidence of testicular cancer--birth cohort effects.
AB  - The incidence of testicular cancer is rising in most Western populations. A
      collaborative study between nine population-based cancer registries in countries
      around the Baltic Sea was utilized in order to analyze in detail geographic
      variations and temporal trends in the occurrence of testicular cancer. There were
      34,309 cases registered up until 1989 starting in Denmark in 1942 and most
      recently in Latvia in 1977. From the descriptive epidemiology it was obvious that
      there was a substantial variation in the age-standardized incidence amounting to
      about a 10-fold difference between the different countries ranging from 0.8 per
      100,000 person-years in Lithuania to 7.6 per 100,000 person-years in Denmark.
      Previous studies have indicated that this increase is due to birth cohort
      effects. A more detailed analysis was therefore performed in those six countries
      with a sufficiently long period of cancer registration; Poland, former East
      Germany, Norway, Finland, Denmark and Sweden. This analysis showed that birth
      cohort is a more important determinant of testicular cancer risk than year of
      diagnosis. In Poland, former East Germany and Finland, there was an increasing
      risk for all birth cohorts. Among men born in Denmark, Norway or Sweden between
      1930 and 1945, this increasing trend in risk was interrupted in these birth
      cohorts but followed thereafter by an uninterrupted increase by birth cohort. In
      conclusion, life time exposure to environmental factors which are associated with
      the incidence of testicular cancer appear to be more related to birth cohort than
      to year of diagnosis. Because testicular cancer typically occurs at an early age,
      major etiological factors therefore need to operate early in life, perhaps even
      in utero.

PMID- 9524584
TI  - Trends in sex-ratio, testicular cancer and male reproductive hazards: are they
      connected?
AB  - In the last few decades, the male proportion of newborn babies has been
      decreasing in several populations. The changes are very small and without
      practical importance per se, but the underlying biological mechanisms are not
      known. In the same period, testicular cancer incidence has increased, and there
      has been indications of decreasing sperm counts in men in several populations.
      The available knowledge on factors that influence the sex-ratio in humans
      supports the idea that an excess of girls in the offspring of a man may be an
      indicator of reproductive hazards. Data from a Danish case-control study show
      strong associations between testicular cancer, low fertility and a low M:F sex
      ratio in the offspring. It is proposed as a hypothesis that there may exist
      common aetiological factors for testicular cancer, low fertility and low
      offspring sex-ratio, and that a search for the causal factors involved may focus
      on agents that can act prenatally to disrupt the normal development and
      differentiation of the male reproductive organs.

PMID- 9524585
TI  - Are estrogens carcinogenic during development of the testes?
AB  - Many chemicals in the environment mimic the female sex hormone, estrogen.
      Exposure to environmental estrogens during early fetal development was proposed
      by Sharpe & Skakkebaek as a potential risk factor for subsequent testicular
      disease, including neoplasia and poor semen quality. To understand the mechanisms
      of action of estrogenic chemicals during differentiation of the male genital
      tract, we have studied developmental exposure to the synthetic estrogen,
      diethylstilboestrol (DES). While DES is a much more potent estrogen than most
      environmental chemicals examined, several of these compounds share some of the
      same properties as DES, such as a relative lack of binding to serum estrogen
      carrying proteins. Prenatal exposure to DES is associated with poor semen
      quality, prostatic disease, cryptorchidism and testicular neoplasia in mice. A
      rare form of testicular cancer, rete testis carcinoma, was observed in five
      percent of male mice treated in utero with DES. We also demonstrated altered
      regulation of an estrogen responsive gene, lactotransferrin (LTF) in the seminal
      vesicles of treated mice, but not the controls. Likewise, LTF was irreversibly
      altered in the uteri of developmentally treated females; at the molecular level
      altered methylation of the gene appears to be involved, thus, providing a
      potential marker for hormonal effects during development. The induction of
      permanent or "imprinted" responses during the development of a relatively
      estrogen-free reproductive tract cell suggests that undifferentiated targets for
      estrogen action may be sites for subsequent growth and differentiation defects
      associated with neoplasia.

PMID- 9524586
TI  - Detection of oestrogenic chemicals by assaying the expression level of oestrogen
      regulated genes.
AB  - The oestrogen receptor belongs to the superfamily of nuclear receptors.
      Classically, nuclear receptors are thought to reside either in the nucleus or in
      the cytoplasm where they interact with their ligand which induces a
      conformational change that exposes the DNA binding domain. This is followed by
      dimerisation and binding of their corresponding response elements. By interacting
      with the transcriptional apparatus they then either activate or repress the
      transcription of target genes. However, this is a highly simplified view, since
      the activated oestrogen receptor interacts with other signal transduction
      pathways and its intrinsic transcriptional activity is highly influenced by
      phosphorylation and by its interaction with other proteins. This is clearly
      observed when the oestrogenicity of antioestrogens is tested since some compounds
      activate the receptor in yeast, but not in mammalian cells. However, when
      specific kinases are activated antioestrogens can also function as oestrogens in
      mammalian cells. Moreover, components of the MAP kinase and perhaps the cAMP and
      other pathways are activated before the receptor even enters the nucleus. Thus,
      when analysing the effects of oestrogenic compounds, it is important to assay
      both their potency as activators of transcription as the effects caused by
      interactions with other signal transduction pathways. This may be possible by
      combining assay methods, such as direct in vitro measurement of interaction
      between a potential oestrogenic chemical and the receptor or the yeast E-screen,
      with methods that are based on mammalian cells or whole animals. An alternative
      is to assay gene expression directly by methods such as differential display,
      where the expression of both genes known to be regulated directly by the receptor
      and genes regulated by other pathways can be monitored. Thereby it may be
      possible to assign different responses to the activation of distinct pathways.

PMID- 9524587
TI  - Negative feedback control of the spermatogenic progression by testicular
      oestrogen synthesis: insights from the shark testis model.
AB  - The organisation of the testis of the dogfish shark is technically advantageous
      for stage-by-stage analysis of spermatogenesis in vivo and in vitro. Prior
      studies using this model show that total oestrogen receptors (ER) are
      concentrated in regions where spermatocysts ("follicle-like" germ cell-Sertoli
      cell units) are in stem cell and spermatogonial stages: respectively, germinal
      zone (GZ) and premeiotic (PrM) regions. By contrast, key enzymes regulating
      oestrogen (E) concentrations (aromatase, 17 alpha-hydroxylase) are maximal in
      meiotic (M) and postmeiotic (PoM) regions, respectively, which are upstream in
      the intratesticular vascular pathway. To investigate the hypothesis that E is
      part of a signalling mechanism between stages of development, studies were
      undertaken to test direct effects of oestradiol-17 beta (E2) on processes in ER
      rich regions. As measured by [3H]thymidine (-Tdr) incorporation. DNA synthesis in
      GZ and PrM regions was inhibited by E2 (0-1000 nM) in a dose-response fashion.
      The maximal response (30-40%) was significant, reproducible and observed within
      72 hr of treatment. Insulin differentially affected DNA synthesis and the
      response to E2 in GZ in GZ and PrM regions. As measured by [3H]Tdr release after
      prelabelling spermatocysts of GZ regions, apoptosis progressively decreased with
      increasing concentrations of E2. At the maximal dose of E2 used, there was no
      effect on total protein synthesis or secretion in combined GZ/PrM cysts,
      indicating that effects on DNA synthesis and cell death were authentically
      physiological, not pharmacological, and consistent with a state of developmental
      arrest. These results support the hypothesis that E synthesised within the testis
      is part of a negative feedback regulatory mechanism whereby more mature stages
      regulate the developmental advance of less mature stages. A growth control
      mechanism of this type could explain the strict temporal, spatial and
      quantitative order of succeeding stages characteristic of normal spermatogenesis
      in all vertebrates. Further study is required to determine whether E signalling
      in this model is restricted to Sertoli cells or has a germ cell component.

PMID- 9524589
TI  - [Pietro Cignolini: the present-day relevance of a Master].

PMID- 9524590
TI  - [Is it a joke? The biodiversity of Radiology Congresses].

PMID- 9524588
TI  - The 4th Copenhagen Workshop on Carcinoma in situ and Cancer of the Testis:
      concluding remarks.
AB  - The 4th Copenhagen Workshop "Carcinoma in situ Germ Cell and Testicular Cancer:
      Molecular and Endocrine Aspects" was held in Copenhagen, Denmark, May 18-21,
      1997. This paper discusses the major themes that emerged during the workshop and
      summarises the most important contributions.

PMID- 9524591
TI  - [Role of magnetic resonance in the evaluation of the normal and osteochondrosis
      hip in early and late childhood].
AB  - INTRODUCTION: Despite MR potentials, few studies investigate the features of
      normal hips and of hip osteochondrosis in early and late childhood. We report our
      personal experience with MRI of hip osteochondrosis in pediatric patients.
      MATERIAL AND METHODS: MR images were obtained with total body MR equipment at
      medium and high fields. The normal hips were studied in children aged 34 months
      to 6 years with abdominal-urinary tract disorders and in 9 patients of the same
      age with unilateral Perthes disease. Hip osteochondrosis was studied in 6
      children with Catteral's type III and IV and in 3 with type I and II disease.
      General anesthesia was never necessary to perform MRI. RESULTS: MRI exactly
      defined the cephalic anatomic profiles of normal hips which are not depicted with
      conventional radiography before the femoral head cartilage ossifies completely.
      MR contrast resolution was very high in depicting the maturation of the
      epiphyseal nucleus and its exact site in the cartilagineous epiphyseal hemisphere
      proximal to the femur. The analysis of MR morphological and structural changes
      permitted to correlate MR findings with the histopathologic features described in
      the literature. In addition, MRI of childhood hip osteochondrosis showed maked
      structural changes of the epiphyseal nucleus which are usually missed with
      conventional radiography. MRI permits early location of the abnormal area and the
      recognition of growing disk abnormalities; it also shows the whole cephalic
      cartilage and the changes of the epiphyseal nucleus evolution, which permits to
      differentiate osteochondrosis evolution from recessive patterns. Finally, MRI
      clearly showed the increased equatorial diameters of the involved femoral heads
      and the associated decrease in polar diameters, which is essential to study the
      biomechanics of hip osteochondrosis and therefore to plan treatment. CONCLUSIONS:
      MRI, even with coronal sequences and T1-weighting only, permits: 1) to image
      normal hips and hip osteochondrosis, especially in early and late childhood; 2)
      to clearly define cephalocotyloid relationships; 3) to depict the actual anatomic
      margins of the head and its structure; 4) to investigate the head cartilage
      extent and to locate the ossification nucleus. These morphologic and structural
      data are very useful to diagnose and manage hip osteochondrosis in the evolutive
      age. MRI shows abnormal changes in anatomic structures which are not seen with
      conventional radiography and demonstrates the evolution of the osteochondrosis
      process over time. In children over six, at the end of the ossification process
      of the head cartilage, conventional radiography alone is often sufficient to
      depict cephalocotyloid relationships and the MR diagnostic criteria of bone
      cephalic diseases are similar to those used in adult hip studies.

PMID- 9524592
TI  - [Three-dimensional reconstructions using spiral computerized tomography in the
      study of craniostenosis. Preliminary experience and technical considerations].
AB  - INTRODUCTION: Craniostenosis is a complex association of syndromes and isolated
      diseases characterized by premature closure of cranial sutures. Three-dimensional
      (3D) Computed Tomography (CT) reconstructions have been widely used for years in
      the preoperative assessment and postoperative follow-up of craniostenosis,
      because of their effectiveness and diagnostic accuracy. Our study concerns the
      acquisition and reconstruction techniques of spiral CT images. This technique
      provides optimal diagnostic results allowing reduction of the radiation dose to
      the patient and of the sedation time. MATERIAL AND METHODS: May, 1995, to
      September, 1996, twelve patients with abnormal cranial growth or suspected
      craniostenosis underwent spiral CT examinations, with 3D reconstructions.
      Fourteen examinations were performed, including two postoperative investigations.
      Our diagnostic protocol consisted of images with 3 mm slice thickness, 3 mm slice
      interval, 2 s scan time, with 180 mAs, 120 kV. The images were reconstructed at 1
      mm intervals. RESULTS: According to the literature, this technique is safe enough
      relative to the dose to the patient (12.2 mSv) and permits to obtain good quality
      3D reconstructions and adequate images of the brain and liquor spaces. Simple
      sedation was sufficient in all cases, using pentobarbital, 2-3 mg/kg.
      CONCLUSIONS: The Authors emphasize the diagnostic effectiveness and accuracy of
      spiral CT with 3D reconstruction in the study of craniostenosis, which also
      permits imaging of the brain and liquor spaces with minimal loss of information.

PMID- 9524593
TI  - [Potential uses of color Doppler in periskeletal soft tissue neoplasms].
AB  - Integrated imaging plays a fundamental role in the study of periskeletal soft
      tissue tumors, for both diagnosis and treatment planning. The steady and
      progressive technologic progress of color Doppler US equipment now permits the
      integration of conventional morphostructural parameters with the biofunctional
      data of lesion flow patterns and relative qualitative features. To assess color
      Doppler capabilities in differentiating benign from malignant soft tissue tumors,
      we reviewed the B-mode and color Doppler findings of 43 consecutive patients with
      a palpable periskeletal soft tissue mass. All patients were examined with a real
      time unit (Ultramark 9 HDI), with a broadband (5-10 MHz) linear transducer
      operating at 6.5 MHz for Doppler measurements. The PRF was set at 1500 to 800 Hz
      with 70% color gain; a 100 Hz wall filter was used. We kept the color box in the
      area of interest as small as possible to keep the frame rate high; pulsed Doppler
      studies were performed with a small sample volume and 2000 Hz PRF. The following
      signs were considered: morphostructural features; the presence/absence of color
      signals; the (peripheral/internal) site of vascular branches, their caliber and
      course; the number of afferent vascular poles; resistance index. As a rule,
      malignant masses tend to differ from benign masses for the presence of multiple
      vascular afferent branches, especially if they have an irregular pattern and
      caliber, and for the variability of the resistance index measured in different
      parts of the same mass. Further examinations, performed with second level imaging
      (CT and MRI) and microhistologic tests, respectively after biopsy and surgical
      resection, confirmed the high predictive value of color Doppler US, with only 1
      false negative and 2 false positives; color Doppler sensitivity and specificity
      were 94.7% and 91.6%, respectively, which are higher values than those obtained
      with US alone (63% and 66.6%). Therefore, we believe that color Doppler US can be
      systematically applied to the study of periskeletal soft tissue masses,
      integrating conventional US for the correct selection of the patients to be
      submitted to second level investigations.

PMID- 9524594
TI  - Helical versus conventional CT in detecting meniscal injuries.
AB  - PURPOSE: We compared volumetric helical and conventional CT in the study of
      meniscal injuries. MATERIAL AND METHODS: Thirty-three patients with suspected
      meniscal tear underwent helical and conventional CT. Common parameters were 512 x
      512 matrix, 14-15 cm FOV, 120 kV and 175 mA; helical CT was performed with 2 mm
      beam thickness, 1.5 mm/s table feed, 1 mm reconstruction index and conventional
      CT with 2 s scan time, 1 mm slice thickness and 1 mm table feed. All scans were
      photographed with a Laser printer using the same window (180/100). All patients
      also underwent sagittal and coronal T2* GE MRI at .5-T; slice thickness was 5 mm
      and interslice gap 1 mm. Nonparametric scales were used to study the menisci, as
      follows: for CT we had A = no visible injury; B = diffuse hypodensity
      (degenerative condition); C = questionable meniscal tear; D = unquestionable
      meniscal tear. For MRI, we had A = no visible injury; B = grade 1 or 2 injury; C
      = grade 3 injury; D = grade 4 injury. We used the 1-4 MR grading by Lotysch et
      al. and by Crues et al. MRI was used as the gold standard. The agreement between
      helical CT, conventional CT and MRI was calculated with kappa statistics.
      RESULTS: Helical and conventional CT found 23 and 15 patterns A, 6 and 10 B, 3
      and 1 C and 1 and 7 D, respectively. MRI found 15 A, 8 B, 3 C and 7 D. There was
      no agreement between helical CT and MRI and between helical CT and conventional
      CT because of the meniscal tears underestimated by the former. Agreement was very
      high between conventional CT and MRI (p < .001). DISCUSSION AND CONCLUSIONS: The
      main result of our experience is that helical CT appears less sensitive than
      conventional CT in detecting meniscal tears. The helical CT section profile (more
      roundish than that of conventional CT) and the lower radiation dose used by
      helical CT (with increased quantum noise) may have played a key role in its
      underestimation of meniscal tears.

PMID- 9524595
TI  - [Significance of the circumferential involvement of the superior horn tip of the
      thyroid cartilage in pharyngo-laryngeal cancer].
AB  - The term "laryngopharyngeal carcinoma" indicates an advanced tumor involving both
      the supraglottic larynx and the pharynx in which the lesion origin may be
      difficult to assess. In 1981, Larsson et al. reported on the CT signs useful to
      distinguish the laryngeal/hypopharyngeal origin of advanced laryngopharyngeal
      carcinoma. We describe a new CT sign which may serve this purpose, namely the
      involvement of the thyroid cartilage superior horn tip. The thyroid cartilage
      superior horn, in fact, is involved early in the lesions originating in the
      pyriform sinus because of its close anatomic relationship with the posterolateral
      wall of the hypopharynx. MATERIALS AND METHODS. To assess the significance and
      specificity of this sign, we examined 15 patients with advanced laryngopharyngeal
      carcinoma with clinical, endoscopic and surgical evidence suggestive of tumors
      originating in the pyriform sinus. All CT examinations were performed with
      contiguous 4 mm slices before and after i.v. administration of iodinated contrast
      agents. Eighteen patients with surgically confirmed advanced supraglottic
      carcinoma were also examined. RESULTS: The thyroid cartilage superior horn tip
      was involved only in 3/18 supraglottic carcinoma patients; transcommissural
      infiltration of the larynx, involving both pyriform sinuses, was found in 2 of
      these cases and extensive invasion of the whole thyroid cartilage and of the
      cricoid ring in 1 case. CONCLUSIONS: The thyroid cartilage superior horn tip is a
      reliable sign of the pyriform sinus origin of advanced laryngopharyngeal cancer
      which is both sensitive (100%) and specific (83%). Moreover, this sign could play
      a major role because it represents, in most cases, the only and earliest sign of
      cartilage involvement. Finally, the encasement of the thyroid cartilage superior
      horn tip by abnormal tissue indicates tumor spread beyond the posterior
      pharyngeal wall. Therefore, these data can be very important for its early
      detection and useful for subsequent surgical planning.

PMID- 9524596
TI  - [Computerized tomography in the evaluation of the larynx after surgical treatment
      and irradiation].
AB  - INTRODUCTION: The follow-up of the patients submitted to surgery for laryngeal
      carcinoma requires both clinical and CT examinations, particularly in the cases
      at high risk of recurrence. Our series consisted of 72 laryngeal carcinoma
      patients operated on and regularly followed-up with CT to distinguish relapse
      from normal or abnormal postoperative changes. MATERIALS AND METHODS: Seventy-two
      laryngeal carcinoma patients were submitted to surgery: total laryngectomy was
      performed in 33 cases, supraglottic laryngectomy in 16 cases, Labayle subtotal
      laryngectomy in 18 cases and Mayer Piquet subtotal laryngectomy in 5 cases. The
      patients were followed-up postoperatively with CT and 94 examinations were
      performed in all; pathology was performed in all the cases with radiologic
      suspicion of recurrence (19 patients) and further clinical examinations were
      performed to exclude recurrence in the 14 cases where imaging findings were
      questionable. RESULTS AND DISCUSSION: Local recurrences were confirmed in 16 of
      19 patients with positive CT findings. Radiologically, the recurrence appeared as
      an irregular thickening of the pharyngo-laryngeal wall with inhomogeneous density
      after i.v. contrast agent infusion. The patients submitted to total or
      supraglottic laryngectomy recurred most often at the cranial site of resection
      (5/6 cases), those submitted to Labayle surgery at the mucosa adjacent to the
      cricoarytenoid unit (3/3 cases) and those submitted to Mayer Piquet surgery in
      the supraglottic region. Two more patients submitted to emergency tracheotomy
      recurred at this level. Lymph node recurrences were found in 6 total laryngectomy
      patients. Misinterpretations were most frequently due to postirradiation changes
      (5 of 14 cases) or to atypical postoperative images (4/14 cases). Three more
      patients presented a secondary lesion misinterpreted as a relapse. CONCLUSIONS:
      Our results confirm the role of CT in the follow-up of the patients operated on
      for laryngeal carcinoma when CT findings are closely correlated with clinical and
      endoscopic results, permitting to correctly assess the extent of relapse and
      possible nodal spread.

PMID- 9524597
TI  - [Perforation of the laryngeal mucosa caused by closed trauma: comparison of
      laryngoscopic and CT findings].
AB  - INTRODUCTION: Laryngeal mucosal perforation is a frequent event whose diagnosis
      is based on clinical, laryngoscopic and CT findings. MATERIAL AND METHODS: We
      reviewed retrospectively the data relative to 77 patients with blunt neck trauma
      examined October, 1991, to June, 1996. All patients were submitted to clinical
      examination first and then, to fiberoptic laryngoscopy and CT on the clinician's
      request. RESULTS: Nineteen patients with small skin tears and no signs and
      symptoms of laryngeal injury were immediately discharged while 37 patients were
      submitted to surgery: 17 to remove cerebral hematomas, 13 to stabilize cervical
      fractures and 7 because of hemodynamic instability. Twenty-one patients underwent
      laryngoscopy which showed laryngeal lesions in 12: wide mucosal disruption with
      fractures of the laryngeal skeleton and hematomas were observed, which needed
      immediate surgery with airway reconstruction in 7 cases; small mucosal tears and
      hematomas were seen and laryngeal CT examination was requested to establish the
      possibility of conservative management in 5 cases which are the subject of the
      present study. Laryngoscopic findings were: 1) laryngeal mucosal tear near the
      thyroid cartilage with quadrangular membrane edema, 2) thyroid mucosal tear with
      thyrohyoid muscle edema, 3) edema of the left false vocal cord, 4) edema of the
      oblique arytenoid muscle, 5) posterior cricothyroid muscle edema with bleeding
      near the cricoid ring. In cases 1, 2 and 3 CT showed gas bubbles in the
      paralaryngeal space, where laryngeal tear or edema were indicated at
      laryngoscopy. DISCUSSION: CT does show the "gas bubbles" in the paralaryngeal
      space when laryngoscopy cannot distinguish laryngeal mucosal perforation from
      tear. CONCLUSIONS: The routine use of CT in minor, laryngeal injuries in the
      emergency department is useful for the early diagnosis of laryngeal mucosal
      perforation.

PMID- 9524598
TI  - [Course of idiopathic pulmonary fibrosis of the Wells grade III at presentation.
      Study using high-resolution computerized tomography].
AB  - PURPOSE: We studied the HRCT and functional evolution of idiopathic pulmonary
      fibrosis (IPF) patients presenting with Wells grade III--prevalent fibrosis.
      MATERIAL AND METHODS: We sequentially studied the HRCT and functional findings of
      16 IPF patients, at presentation and at 1 year. All patients had a typical grade
      III IPF pattern; those with the most severe clinical presentation were treated
      (9/16). The main HRCT parameters were the extent of interstitial involvement and
      emphysema (visual score) and the mean diameter of lung cysts in honeycombing
      regions. RESULTS AND CONCLUSIONS: Most of our grade III IPF patients exhibited a
      slowly progressive deterioration, with no accelerated parenchymal opacification.
      Deterioration was found on HRCT images in 56.2% of patients (p = .02), with a
      mean monthly increase of .56%. Fibrosis extent, evaluated as HRCT visual score at
      presentation, was significantly correlated with viability and PaO2, values (p =
      .01). Follow-up HRCT scores were also significantly correlated with viability (p
      = .004). The mean diameter of honeycomb lung cysts increased in 25% of patients.
      Emphysema was associated at presentation in 50% of patients--all of them former
      smokers; it was less diffuse than interstitial involvement (15% of total lung
      volume versus 46.7% at presentation) and was not seen to progress on follow-up
      images. The comparison between treated (T) and untreated (NT) patients confirmed
      more severe HRCT and functional damage in T patients at presentation. Moreover, T
      patients presented a significantly more rapid deterioration, despite treatment,
      than NT patients, who had less severe and slower HRCT and functional evolution,
      excluding DLCO deterioration (p = .01). To conclude, grade III IPF patients can
      be subdivided into two subgroups, with rather different prognosis and evolution,
      on the basis of HRCT and functional findings at presentation. The current
      treatment seems useless in grade III IPF. HRCT findings, integrated with the
      visual score of disease extent, and lung function tests can be used to monitor
      grade III IPF evolution.

PMID- 9524599
TI  - [Rationalization of the use of preoperative thoracic radiography in obstetrics
      and gynecology].
AB  - INTRODUCTION: Rationalizing preoperative chest radiography remains a problem in
      our Country. Therefore, we tried to use preoperative chest films rationally in
      obstetrics and gynecology to assess their impact on anesthesia planning and
      patient management and their use in early postoperative complications. MATERIAL
      AND METHODS: We examined two groups of patients: group A consisted of 570 women
      (mean age: 31 years) scheduled to be submitted to cesarean section but with no
      preoperative chest radiography; group B consisted of 471 patients (homogeneous in
      age to group A patients) submitted to nononcologic gynecologic surgery and with a
      single-projection preoperative chest radiograph. Anesthesiologic assessment,
      preoperative biochemical tests and EKG were performed in all patients. All
      patients underwent abdominal surgery under general anesthesia. The first 24
      postoperative hours were monitored for possible anesthesia-related complications.
      The anesthesiologist need of chest radiography based on clinical findings was
      investigated in group A patients, as well as the importance of chest film
      findings in possible anesthesia-related complications. RESULTS: Group A and group
      B were homogeneous by mean patient age and anesthesia duration; clinical findings
      never suggested the need of chest radiography in group A patients. Three
      cardiorespiratory complications occurred (two respiratory arrests in group A and
      a gas embolism in group B), but the (un)availability of chest film findings made
      no difference in treatment. DISCUSSION: The availability of the preoperative
      chest radiographs of a group of healthy women of 31 years mean age does not make
      any difference in anesthesia planning and type. In our series, the most severe
      cardiorespiratory complications were homogeneous in the two groups, which
      confirms their random character, and the (un)availability of preoperative chest
      film findings made no real difference, even though the lack of radiographic
      evidence made patient management more demanding for anesthesiologists.

PMID- 9524600
TI  - [Comparisons of pulmonary and sinonasal lesions in patients with cystic fibrosis.
      Evaluation using computerized tomography].
AB  - INTRODUCTION: Cystic fibrosis is a recessive genetic systemic exocrinopathy
      caused by a variety of mutations in the cystic fibrosis transmembrane conductance
      regulator gene (CFTR). The disease is characterized by alterations of the
      secretions, which become thickened and viscous. Both the paranasal sinuses and
      the lung parenchyma are involved in all cases. The aim of this study was to
      assess a correlation between the rhinosinusal and lung parenchyma changes in
      cystic fibrosis patients. MATERIAL AND METHODS: Eighteen patients (11 men and 7
      women, age range: 8 to 22 years) were examined with chest HRCT and sinonasal low
      dose CT. Lung symptoms were found in all patients; 13 of them, also affected with
      rhinosinusal symptoms, had been examined with ENT and nasal endoscopy. The other
      5 patients, without rhinosinusal symptoms and previously examined with ENT, were
      evaluated as control group. Chest CT was performed with the high-resolution
      technique, 2 mm slice thickness and 10 mm table feed. Rhinosinusal CT was
      performed with the low dose technique, acquiring contiguous 2-4 mm thickness
      coronal sections. The CT patterns were analyzed by two radiologists and scored as
      slight, medium and diffuse involvement of both districts. RESULTS: No
      statistically significant correlation between lung and sinonasal damage was found
      in our study. Parenchymal lung involvement appeared more severe than sinonasal
      involvement in 14/18 patients. The retention of secretions in the paranasal
      sinuses, even if limited, was demonstrated in all symptomatic and asymptomatic
      patients. CONCLUSIONS: The absence of correlation between pulmonary and sinonasal
      damage and more generally, the different severity of cystic fibrosis can be
      caused by different allele mutations of the cystic fibrosis transmembrane
      conductance regulator gene, the most frequent of which is Delta F-508.

PMID- 9524601
TI  - [Quantitative evaluation of flow in the portal vein. Comparison of bolus tracking
      magnetic resonance and Doppler color ultrasound].
AB  - PURPOSE: Magnetic resonance angiography (MRA) can be used to measure flow
      velocity in the portal vein noninvasively. Our study was aimed at measuring mean
      flow velocity in the portal vein and section area and overall portal flow with
      bolus tracking MRA versus color Doppler US. MATERIAL AND METHODS: Twenty healthy
      volunteers were submitted to presaturation bolus tracking MRA and color Doppler
      US before and after a 1500 Kcal meal. The images were acquired during breath
      holding and analyzed prospectively for the following parameters: mean flow
      velocity, portal vein caliber and flow, before and after a meal. MRA measurements
      were made on both baseline images and MIP reconstructions. RESULTS: Before the
      meal, mean portal flow velocity was 17.07 +/- 3.01 cm/s with MRA versus 17.46 +/-
      3.12 cm/s with color Doppler US (r = .85). After the meal, mean velocity was
      24.52 +/- 3.8 cm/s with MRA and 24.8 +/- 4.0 cm/s with color Doppler US (r =
      .85). After the meal, portal velocity increased by 44% with MRA and by 42% with
      color Doppler US. Before the meal, the portal vein section area was 1.27 +/- .32
      cm2 with MRA and 1.17 +/- .29 cm2 with color Doppler US (r = .86), versus 1.52 +/
      .30 cm2 with MRA and 1.44 +/- .27 cm2 with color Doppler US (r = .85) after the
      meal. Portal vein flow was 1248.4 +/- 302.46 mL/min with MRA and 1202.85 +/-
      316.12 mL/min with color Doppler US before the meal, versus 2252.45 +/- 523.90
      mL/min with MRA and 2202 +/- 576.74 mL/min with color Doppler US (r = .91) after
      the meal. Portal vein flow increased by 78% with MRA versus 83% with color
      Doppler US after the meal. DISCUSSION AND CONCLUSIONS: Bolus tracking MRA is an
      accurate method to quantitate mean velocity, section area and blood flow in the
      portal vein.

PMID- 9524602
TI  - [MR cholangiopancreatography: technique, indications and clinical results].
AB  - INTRODUCTION: MR cholangiopancreatography (MRCP) is a new noninvasive imaging
      technique for the study of biliopancreatic disorders, providing projectional
      images of the biliary tree and pancreatic duct without any contrast agent.
      MATERIAL AND METHODS: We used different sequences, with both breath-hold and
      nonbreath-hold techniques, to acquire MRCP images, first based on GE and then on
      FSE sequences. FSE images provide higher SNR and are less susceptible to
      artifacts (metal objects, motion and blood flow artifacts). At the Department of
      Radiology of the University of Rome La Sapienza, we acquired MRCP images with non
      breath-hold, 3D fat-suppressed TSE sequences (TR = 3000-2000, TE 700, turbo
      factor 128) optimized on a .5T magnet with 15 mT/m gradients. No patient
      preparation or sedation was required, although antiperistaltic drugs and oral
      administration of tap water were preferred. Four hundred and thirty patients were
      examined, all of them with an indication to conventional cholangiography.
      RESULTS: MRCP depicted the whole common bile duct and the first-order
      intrahepatic branches in all the normal cases. Its accuracy in identifying
      biliary obstruction level and site was 100%, versus 94.6% in characterizing its
      cause. MRCP had 96.3% diagnostic accuracy in choledocholithiasis, with some false
      positives and false negatives caused by: 1) small stones missed on MIP
      reconstructions; 2) signal loss due to complete CBD obstruction by stones; 3)
      pneumobilia; 4) differential diagnosis between small stones and air bubbles. The
      main role of MRCP in benign strictures is to provide a detailed map of the
      biliary tract for better treatment planning. In particular, MRCP is extremely
      useful in hepaticojejunostomy patients, where ERC is not indicated because of
      postoperative anatomical changes. Both conventional MRI and MRCP are important in
      malignant strictures to identify the lesion and to characterize and stage it.
      Finally, MR pancreatography is very useful to follow up chronic pancreatitis
      patients because it shows Wirsung duct strictures and dilatations, intraductal
      filling defects and, in some cases, the communication between the pseudocyst and
      the pancreatic duct. CONCLUSIONS: MRCP combined with conventional MRI can
      completely replace CT and ERCP in bilio-pancreatic disorders.

PMID- 9524603
TI  - [Adrenal involvement in renal carcinoma. Diagnostic value of computerized
      tomography].
AB  - PURPOSE: We investigated the sensitivity and specificity of computed tomography
      (CT) in the detection of ipsilateral involvement of the adrenal glands by renal
      cancer. MATERIAL AND METHODS: We reviewed 350 cases of radical nephrectomy for
      renal cancer; the adrenal gland had been removed during nephrectomy in 185 cases.
      RESULTS: Histology confirmed adrenal gland involvement from renal cancer in 9
      cases, namely 4 metastatic nodules and 5 cases of direct tumor invasion. Adrenal
      involvement was identified by preoperative CT in 3 cases only: the gland was
      undetectable in 2 of them, being masked by a large tumor mass, while it appeared
      normal on CT images in the 4 patients with metastatic nodules. CONCLUSIONS: An
      adrenal gland appearing normal during preoperative CT assessment of renal cancer
      is not very likely to be involved by cancer (2.4% of cases in our series), while
      a gland missed at CT is very likely involved because it may be masked by a large
      tumor.

PMID- 9524604
TI  - [Does B-mode ultrasound still have a role in the diagnosis of spermatic cord
      torsion? Findings in a pediatric series].
AB  - INTRODUCTION: Acute scrotum in the pediatric age is mainly related to surgical
      causes. Spermatic cord torsion and inguinoscrotal hernia must be ruled out first,
      because of the possible ischemic damage to gonadal tissue and therefore surgery
      is sometimes performed directly, thus representing also a diagnostic tool.
      Spermatic cord torsion is found in two age ranges, namely: the neonatal period,
      where it usually represents the evolution of an intrauterine process, and the
      peripubertal period, which is more frequent. An unquestionable and prompt
      diagnosis is particularly needed because of the extreme sensitivity of gonadal
      tissue to ischemia. In this particular field, color and power Doppler US,
      depicting gonadal flow, have greatly increased diagnostic imaging capabilities,
      which were previously limited to B-mode US. MATERIAL AND METHODS: We examined 19
      peripubertal patients with the diagnosis of spermatic cord torsion made on the
      basis of B-mode US and then confirmed with color Doppler. RESULTS: We found two
      signs which can be considered highly suggestive of spermatic cord torsion: the
      spiral twist of spermatic vessels and the peculiar extent of reactive hydrocele,
      caused by the bell clapper anomaly of the vaginal sac. CONCLUSIONS: The above US
      patterns are very helpful to diagnose spermatic cord torsion.

PMID- 9524605
TI  - [Thymic carcinoid: CT and MR findings].
AB  - PURPOSE: We studied the CT and MR appearance of thymic carcinoids and compared
      the morphostructural patterns of this tumor with those of other anterior
      mediastinal masses particularly involving the thymic area. MATERIAL AND METHODS:
      We retrospectively reviewed all the chest CT scans performed 1985-1996. Four
      patients (2 women and 2 men; age range: 25-51 years, mean: 36.5) had thymic
      carcinoid. MR findings were also available for 3 of 4 patients. The pathologic
      diagnosis was made in all cases, by CT-guided needle biopsy (1 case), by surgical
      biopsy (2 cases), or directly at surgery (1 case). RESULTS: CT showed capsulated,
      quite enhanced tumors with no local spread or distant metastases in 1 case; 2
      tumors appeared as complex masses with necrotic components and calcifications,
      massively invading mediastinal structures; another case appeared as an
      infiltration of mediastinal fat and vessels with no definite tumor mass.
      Thrombosis of the superior vena cava and right atrium and some lung metastases
      were found in one case. MR signal was hypointense on T1 and PD images and
      inhomogeneously hyperintense on T2 images in all the 3 patients. One patient had
      Cushing syndrome and another mild adrenocortical hyperfunction. The other
      patients had no endocrine dysfunctions. Both the patients treated with surgery
      and subsequent irradiation are alive and free of relapse at 48 and 17 months,
      while the other 2 patients died 25 and 39 months after the diagnosis.
      CONCLUSIONS: The CT and MR patterns of thymic carcinoids are not specific because
      other mediastinal and particularly thymic tumors present similar patterns.
      However, a thymic carcinoid must be suspected when a thymic mass is associated
      with clinical laboratory findings of endocrine dysfunction.

PMID- 9524606
TI  - [Preliminary results of preoperative radiotherapy schedule in the treatment of
      rectal tumors].
AB  - From March, 1988, to October, 1993, fifty-six consecutive patients with rectal
      adenocarcinoma in clinical stage T3NxM0, underwent preoperative radiation therapy
      at the "Casa Sollievo della Sofferenza" Hospital of San Giovanni Rotondo (Italy).
      The patients were treated with the four-field technique with 6 to 8 MV X photons
      on the pelvis. The dose given was 36 Gy in 12 fractions of 3 Gy each. Surgery was
      performed 2-3 weeks after completion of radiotherapy. Six patients were excluded
      from this study for metastatic involvement of the liver found at surgery. 48% of
      50 assessable patients underwent abdominoperineal resection and 52% anterior
      resection. 68% of patients were in pathologic stage pT0-3 pN0 and 32% in pT0-3
      pN1-2. Metastatic nodes were found in 16 patients (32%) (11 pN1 and 5 pN2). 4% of
      patients achieved a complete response. The follow-up ranged 24 to 91 months
      (mean: 46 months). None of the 50 patients died during the postoperative period
      and the specific morbidity was 26%. Side-effects, requiring surgery, were found
      in 4% of patients (1 retroperitoneal fibrosis and 1 small bowel occlusion). The
      incidence of local relapse was 8%. The overall survival at 5 years, in all
      stages, calculated with the Kaplan and Meyer method, was 76.5%. The disease-free
      survival rate was 81.1% in all stages: 94.1% in pT0-3 pN0 patients and 54.1% in
      pT0-3 pN1-2 patients. The disease-free survival rate related to nodal involvement
      was 72.7% in pN1 patients and 20% in pN2 patients. Our experience confirms the
      effectiveness of preoperative radiation therapy to improve local control in
      rectal cancer patients. In the future, it will be useful to assess the impact on
      prognosis of the schedules using chemotherapy, different fractionation of
      radiotherapy, delayed surgery and biological predictors of response to
      irradiation.

PMID- 9524608
TI  - [Para-articular ossifications in the comatose patient. Clinico-radiographic
      aspects in a case report].

PMID- 9524607
TI  - [Errors in positioning the patient during transcutaneous radiotherapy of the
      pelvis].
AB  - INTRODUCTION: Quality controls in radiotherapy allow to check the correct running
      of treatment units and to test our procedures. Portal films taken during the
      first treatment session are used in quality assurance programs to compare
      scheduled to administered doses. MATERIAL AND METHODS: To analyze the accuracy of
      patient positioning in pelvic cancer irradiation, a retrospective study was
      carried out on 50 treatment schedules carried out at the Radiotherapy Department
      of S. Anna Hospital (Como, Italy) from June to December, 1996. We checked field
      mispositioning for correlations with patient or treatment variables, such as
      patient age, sex, weight, thickness, or unit type. We took one portal film at the
      first treatment session and checked field positioning by measuring the distance
      of the isocenter from fixed anatomical structures on the simulation film and on
      the portal film taken in anteroposterior and lateral projections. RESULTS: Four
      vectors were defined to evaluate field mispositioning along right-left (ADS),
      craniocaudal (ACC, LCC) and anteroposterior (AP) directions. The average values
      of these four vectors were respectively 2.94, 5.23, 5.54 and 3.20 mm. We found a
      major shift in field centering leftward and toward the patient's feet. To obtain
      more information about the total isocenter displacement, a vector T was
      calculated by summing the vectors ADS, ACC and LAP; a further evidence of field
      mispositioning is given by the vector T mean value (8.66 +/- 4.95 mm). No
      correlation was found between vector T values and any patient or treatment
      variable. DISCUSSION: The acquaintance with uncertainties requires adequate
      statistical tools. A single check at treatment beginning could show a systematic
      error, but not the random fluctuations which can be recognized only with periodic
      portal films. To correct a possible systematic error without likely worsening set
      up conditions, an adequate threshold value must be chosen for field
      mispositioning, according to each center's historical data. CONCLUSION: One
      portal film at the beginning of treatment is the minimum requirement in a quality
      assurance program. We feel the need to change our protocol and acquire more than
      one portal film, because the higher the number of portal films the easier the
      distinction of systematic from random errors. Using serial portal films, all at
      the first session, we will be able to introduce quantitative criteria for various
      action levels.

PMID- 9524609
TI  - Shprintzen-Goldberg syndrome. A case report.

PMID- 9524610
TI  - [Tibial sarcoidosis. Radiologic and magnetic resonance aspects].

PMID- 9524611
TI  - [A case of meningioma appearing as a cyst with solid parietal nodule. Evaluation
      using computerized tomography and magnetic resonance].

PMID- 9524612
TI  - Diffuse panbronchiolitis. An Italian experience.

PMID- 9524613
TI  - [Pulmonary hydatidosis with spinal involvement. A case report].

PMID- 9524614
TI  - [Diffuse pulmonary hemorrhage associated with antineutrophil cytoplasmic
      antibodies. Findings of high-resolution computerized tomography. A case report].

PMID- 9524616
TI  - [Kaposi's sarcoma with splenic localization. CT pattern in a case].

PMID- 9524615
TI  - [Fat accumulation in the gastric submucosa secondary to chemotherapy. A case
      report documented by computerized tomography].

PMID- 9524617
TI  - [Inguino-scrotal hernia of the ureter. A case report with computerized tomography
      findings].

PMID- 9524618
TI  - [Role of magnetic resonance in retrovascular goiter. 2 case reports].

PMID- 9524619
TI  - [Endovascular Ir-192 HDR brachytherapy for avoidance of intimal hyperplasia in
      peripheral vessels after PTA and stent implantation. A 6-year experience].
AB  - BACKGROUND: The percutaneous transluminal angioplasty (PTA) is the "golden
      standard" in the therapy of vessel occlusions due to arteriosclerotic plaques. In
      spite of all improvements of the technique and the equipment with and without
      stent implantation there is still a restenosis rate of 40%. PATIENTS AND METHODS:
      Endovascular brachytherapy with an iridium-192 HDR source was performed in cases
      of a restenosis due to intimal hyperplasia which occurred within 6 months after a
      former PTA. After PTA and stent implantation a 9-French ReKa catheter was
      positioned with the tip 2 cm below the stent. This catheter served a centering
      device and as a guide for the 5-French applicator. After determination of the
      isodose and individual planning a dose of 12 Gy to 3 mm source distance was
      applied. After this procedure the patient received heparin for 72 hours followed
      by marcumar. RESULTS: From May 1990 until June 1996 28 patients (21 male, 7
      female) were treated after PTA and stent implantation with endovascular
      brachytherapy. All patients had clinical relevant restenosis or reocclusion of
      the arteria femoralis. The follow-up time ranges from 2 to 71 months. Twenty
      seven patients had a reasonable follow-up time longer than 6 months. Twenty-five
      patients could be followed: 4 patients had no or only minimal flow in the treated
      area, 2 patients moved with an unknown address, 1 patient died without any follow
      up examination. No side effects of the radiation appeared. CONCLUSION: Regarding
      the small number of patients endovascular brachytherapy with iridium 192 HDR
      seems to be a save and useful adjuvant treatment form to avoid intimal
      hyperplasia after PTA.

PMID- 9524620
TI  - Radiotherapy alone or radiochemotherapy with platin derivatives following
      transurethral resection of the bladder. Organ preservation and survival after
      treatment of bladder cancer.
AB  - PURPOSE: Multivariate analysis of prognostic factors influencing survival and
      bladder preservation after radiochemotherapy for bladder cancer following
      transurethral resection of the bladder (TURB). PATIENTS AND METHODS: At the
      University Hospital of Erlangen 333 patients with bladder cancer were treated
      with either radiotherapy alone (RT, n = 128) or platin based radiochemotherapy
      (RCT, n = 205) after TURB between 5/1982 and 5/1996. Two-hundred and eighty-two
      curative patients, with either muscle invasive or T1-high risk cancer, were
      analyzed. Median age was 66 years, median follow-up is 7.5 years. Uni- and
      multivariate analysis was performed for age, grade, R-status after initial TURB,
      T-category and treatment modality relevant to the endpoints initial response,
      survival and bladder preservation. RESULTS: Treatment related mortality was below
      1%. Complete remissions were achieved at 57%, 70%, and 85% after RT or RCT with
      carboplatin or cisplatin. This difference was multivariately significant. Further
      significant prognostic factors were pT-category and R-status. For all patients
      survival was 59% and 43% after 5 and 10 years. 79% of survivors could keep their
      own bladder. Five-year survival rates after RT alone, RCT with carboplatin or
      cisplatin were 47%, 57%, and 69%, respectively. This was univariately
      significant. The only multivariately significant factor for survival and bladder
      preservation was the R-status after initial TURB. CONCLUSIONS: Treatment of
      bladder cancer by TURB and RT/RCT is an alternative to primary cystectomy. The
      addition of chemotherapy leads to significantly more complete remissions and
      better survival. Initial TURB is recommended to be as radical as possible.

PMID- 9524621
TI  - [Survival of exclusively irradiated patients with NSCLC. Significance of
      pretherapeutic hemoglobin level].
AB  - BACKGROUND: In a retrospective study files of 96 non-operated, non-small-cell
      lung cancer (NSCLC) patients receiving radiation therapy were statistically
      analysed. A correlation of the pre-therapeutical haemoglobin level and the
      survival of patients after a primary radiation therapy has been described by some
      authors, but it is an open question whether there is any dose-modification in the
      treatment schedule, related to different prognostic subgroups of patients, that
      makes sense. PATIENTS AND METHOD: We have analysed the files of 96 primary
      radiated patients to evaluate the pre-therapeutical haemoglobin level as well as
      sex, age, histopathology, total dose and fractionation. The analysis of Karnofsky
      status or patient condition was not performed as there was a lack of sufficient
      data in the patient files. RESULTS: Histopathology, sex, age as well as total
      dose and fractionation of the radiation treatment were similar in the cohort
      building 3 groups: Hb < 11 g/dl, Hb between 11 to 15 g/dl and Hb > 15 g/dl. The
      investigation resulted in the observation, that lower levels of initial serum
      haemoglobin concentration compared to levels over 15 g/dl are negative prognostic
      factors. Higher initial haemoglobin concentration is a high significant positive
      prognostic factor (p = 0.0001). The applied total dose (> 30 Gy, > 50 Gy, > 55
      Gy) was not a significant prognostic factor in this patient material, where two
      thirds of the patients had an advanced cancer (stage IIIB or stage IV).
      CONCLUSIONS: We conclude that initial haemoglobin concentration is a significant
      prognostic factor for NSCLC patients treated by radiation therapy. Further
      investigations are necessary to determine whether a dose escalation can improve
      the outcome of a subgroup of patients with high-normal haemoglobin levels.

PMID- 9524623
TI  - [Prevention and therapy of acute radiation injuries of the skin and mucosa. I.
      Results of a German multicenter questionnaire].
AB  - BACKGROUND: The acute radiation related morbidity is an essential factor for the
      patient's outcome in radiotherapy. The prophylactic and therapeutic management of
      acute side effects has a wide clinical range between different radiation oncology
      departments. In this work, it was to evaluate the remedies, which are used for
      prevention and therapeutic management of acute radiation related morbidity of the
      skin and mucosa (mouth, pharynx, esophagus, small and large bowel, rectum and
      vagina). METHODS: A questionnaire was sent to 130 radiotherapeutic departments in
      Germany in July 1995. The questionnaire had been designed with 22 open questions
      concerning the preventive and therapeutic management of acute radiation related
      morbidity of skin and mucosal sites. It has been correlated to the scoring system
      of the RTOG/EORTC and its German modification according to Seegenschmiedt and
      Sauer. The evaluation was performed anonymously. RESULTS: From 130
      questionnaires, 89 (68.4%) were sent back till August 1995. All of them were
      evaluable. The recommendations showed a broad spectrum for each site. Especially
      the oral mucositis was treated in many different ways and combinations. The
      prevention and therapy of complicating superinfections seem to be the joint
      principle of most of the recommendations. CONCLUSIONS: The management of the
      acute radiation related morbidity has a wide clinical spectrum among different
      radiation therapy centers. Systematic prospectively designed investigations are
      necessary in order to achieve a further reduction in the radiation related acute
      morbidity. Therefore, a multicenter collaborative working group has been founded.

PMID- 9524622
TI  - [3D-Ct-planned interstitial HDR brachytherapy + percutaneous irradiation and
      chemotherapy in inoperable pancreatic carcinoma. Methods and clinical outcome].
AB  - PURPOSE: Clinical experiences in interstitial 192-iridium HDR brachytherapy for
      the treatment of unresectable pancreatic carcinoma are presented. Brachytherapy
      has been used as boost irradiation in a multimodality treatment concept together
      with external radiotherapy and simultaneous chemotherapy. Practicability during
      clinical routine, tolerability and toxicity of treatment are investigated.
      PATIENTS AND METHODS: Nineteen patients (9 female, 10 male, median age 67 years)
      with unresectable carcinoma of the pancreas have been treated with interstitial
      brachytherapy. Distribution according to UICC stages showed 4, 10 and 5 patients
      in stage II to IV respectively. In all cases afterloading technique with 192
      iridium in HDR-modus was used. A total dose of 10 to 34 Gy to the reference
      isodose was delivered (single dose 1.88 to 5 Gy, median 2.5 Gy). Brachytherapy
      was followed by external radiotherapy, delivering an additional dose of 40 to 58
      Gy. Nine patients received simultaneous chemotherapy (5-fluorouracil,
      leucovorin). Treatment planning was performed based on CT scans, allowing spatial
      correlation of isodose curves to the patient's anatomy. RESULTS: Median survival
      time was 6 months. A trend of lower survival rates with advanced stage of disease
      (median survival stage IV 4 months, stage II and III 6.5 months) was seen. Local
      control rate was 70%. Brachytherapy treatment was well tolerated, severe acute
      side effects were not observed. One patient developed pancreatic fistulae 4
      months and 1 patient a gastric ulcer 7 months after treatment. Pain release was
      achieved in all patients. CONCLUSIONS: 192-iridium HDR-brachytherapy is an
      effective tool in the treatment of unresectable pancreatic carcinoma with a high
      rate of local control and a low rate of side effects and is comparable IORT or
      seed implantation.

PMID- 9524626
TI  - [Preoperative radiotherapy in bladder carcinoma].

PMID- 9524624
TI  - [Prevention of radiochemotherapy-induced mucositis. Value of the prophylactic
      mouth rinsing with PVP-iodine solution].
AB  - BACKGROUND: Oral mucositis is a frequent complication of radiochemotherapy. The
      origin of radiation-induced mucosa lesions is of iatrogenic nature although
      further development of mucositis is essentially influenced by infection. It can
      be assumed that disinfection measures should decrease the severity of mucositis
      induced by radiochemotherapy. Therefore, in a prospective randomised study the
      efficacy of prophylactic oral rinsing with a disinfection agent was investigated.
      PATIENTS AND METHOD: An open, randomised, prospective comparative trial was
      conducted with 40 patients undergoing radiochemotherapy of head and neck region
      due to malignant disease. The treatment scheme consisted of irradiation to tumor
      region and adjacent lymph nodes with a total dose of 71.3 Gy and simultaneous
      chemotherapy with carboplatin (60 mg/m2) on days 1 to 5 and 29 to 34. In all
      patients, a prophylaxis of mucositis with nystatine, rutosides, panthenol and
      immunoglobulin was undertaken. In addition, 20 patients rinsed oral cavity 4
      times daily with povidone-iodine-solution, the comparative group rinsed with
      sterile water. Clinical examination of the oral mucosa was performed weekly.
      Onset, grading and duration of mucositis were used as main variables. RESULTS:
      Clinically manifested oral mucositis was observed in 14 patients of the iodine
      group (mean grading: 1.0) and all 20 patients of the control group (mean grading:
      3.0). Total duration (mean) of clinically observed mucositis was 2.75 weeks in
      treatment patients and 9.25 in control patients. Median AUC (area under curve for
      grade vs duration) was 2.5 in iodine rinsing patients and 15.75 in control
      patients. All differences found between the 2 groups were statistically
      significant. Increased iodine incorporation was not observed. A pathological
      increase of thyroid hormone levels in the iodine group was not found.
      CONCLUSIONS: The gained results indicate that incidence, severity and duration of
      radiochemotherapy-induced mucositis can be significantly reduced by oral rinsing
      with povidone-iodine performed additionally to the standard prophylaxis scheme.

PMID- 9524627
TI  - [Catheter-based radiotherapy to inhibit restenosis after coronary stenting].

PMID- 9524629
TI  - ASLAP addresses Spay Day "controversy".

PMID- 9524628
TI  - [Studies on vision improvement in patients with choroid metastases after
      percutaneous radiotherapy: a multivariate analysis of 188 patients].

PMID- 9524625
TI  - [Significance of apoptotic processes in radiotherapy. I].
AB  - According to a considerable amount of publications apoptosis plays an important
      role for radio- and chemotherapy. The most important results related to this
      issue will be described in 2 independent articles, covering the following topics:
      Part I: I. definition, morphology, biochemical processes, II. clinical relevant
      detection assays, III. signal transduction. Part II: significance of apoptosis
      for radio- and chemotherapy.

PMID- 9524630
TI  - Reader's comments on recent issue.

PMID- 9524631
TI  - Veterinarians and little white lies.

PMID- 9524632
TI  - Microbiologic investigation of enterohemorrhagic Escherichia coli O157:H7
      infection at a zoo.

PMID- 9524633
TI  - What is your diagnosis? Small intestinal intussusception in a quarter horse
      filly.

PMID- 9524635
TI  - Treatment of idiopathic chylothorax in dogs and cats.

PMID- 9524634
TI  - Anesthesia case of the month. Analgesia for fractures until surgery can take
      place.

PMID- 9524636
TI  - Foods and techniques for managing obesity in companion animals.
AB  - Management of obesity should initially involve assessment of the pet to rule out
      other possible medical problems and provide an accurate dietary history. It is
      essential to obtain a good estimate of the existing caloric intake, including
      calories from table scraps, pet treats, or other sources. Assessing the owner's
      willingness to make a commitment to a major lifestyle change for their pet is
      also an important part of any successful weight-reduction program. In some
      instances, this motivation can be linked to a recent, expensive bill for
      orthopedic or other procedures performed on their pet. Once a candidate has
      entered a program, calculated restriction of energy while maintaining protein,
      vitamin, and mineral intake should be recommended. It may be surprising to find
      out that the calculated amounts of food may be more than the amount a pet is
      currently being fed. In these animals, it is imperative to use a high-protein,
      obesity-management diet and not a low-protein, "light," or senior type of diet
      containing high fiber. If possible, treats should be restricted altogether and
      begging actively discouraged. Any snacks should be placed in the pet's feeding
      bowl so that an association between eating and the bowel become established. Of
      equal importance is use of a realistic exercise program that owners will
      encourage their pet to follow. Various products for weight reduction are
      available. Use of these specially formulated products to restrict caloric intake,
      while maintaining essential nutrient intake and increasing energy expenditure by
      playing and other activities, are the hallmarks of successful weight loss
      programs.

PMID- 9524637
TI  - A veterinarian's duty to accommodate the disabled.

PMID- 9524638
TI  - Effect of source of cattle and distance transported to a commercial slaughter
      facility on carcass bruises in mature beef cows.
AB  - OBJECTIVE: To determine the effect of source of cattle and distance cattle were
      transported to a commercial slaughter facility on prevalence and severity of
      carcass bruises in mature beef cows. DESIGN: Epidemiologic investigation. SAMPLE
      POPULATION: Carcasses from 3,955 beef cows from 11 states assembled in 89
      procurement lots. PROCEDURE: Each carcass was scored for bruise severity and
      location. Source of cattle was categorized. Distance from source to slaughter
      facility was determined. An ANCOVA was used to determine effects of variables on
      carcass bruises. RESULTS: Mature beef cows marketed through livestock auctions
      conducting first-point testing for brucellosis, especially when transported
      longer distances (> 325 km) to slaughter facilities, had a greater number and
      severity of carcass bruises than cows originating from ranches or livestock
      auctions not conducting first-point testing. There was an increase in number of
      rib bruises in cows originating from livestock auctions not conducting first
      point testing. Prevalence and severity of bruises were not significantly affected
      by transportation distance between cows originating from auctions not conducting
      first-point testing and cows originating from ranches. CLINICAL IMPLICATIONS: A
      strong association existed between handling for brucellosis testing prior to sale
      for slaughter and distance transported to slaughter facility with carcass bruises
      in mature beef cows. Bruises are major quality defects that decrease carcass
      value and slaughter-cow prices. Repeated handling and restraint as well as long
      distance transport are issues to consider regarding the responsibility of the
      livestock industry to provide for the safety and well-being of cattle sold for
      slaughter.

PMID- 9524639
TI  - Liver lobe torsion and liver abscess in a dog.
AB  - A 4-year-old Rhodesian Ridgeback had acute onset of vomiting, lethargy, and
      discolored urine. Physical examination revealed lethargy, pyrexia, weak femoral
      pulses, cardiac arrhythmia, distended abdomen, and signs of pain on abdominal
      palpation. Abdominal radiography and ultrasonography revealed a gas-containing
      lesion in the cranial portion of the abdomen. Preoperative care included
      administration of fluids, antibiotics, and antiarrhythmic medication. Exploratory
      laparotomy revealed hemobilia and a 360 degrees clockwise torsion of the
      papillary process of the caudate lobe of the liver. Clinical signs resolved
      completely after liver lobectomy, and the dog was alive 2 years after surgery.
      Torsion of a liver lobe is rare in dogs. Necrosis of the involved liver lobe can
      result in acute weakness, shock, and death. Hemodynamic stabilization, antibiotic
      treatment, and surgical intervention have been successful in treating this
      condition. Liver lobe torsion should be considered on the differential diagnoses
      list of acute abdominal pain.

PMID- 9524640
TI  - Neutropenia and thrombocytopenia in three dogs treated with anticonvulsants.
AB  - Three dogs became lethargic and had poor appetites within 2 months after
      anticonvulsant treatment was initiated to control seizures. Dogs were
      neutropenic, thrombocytopenic, and anemic and had splenomegaly. Sensitivity to
      phenobarbital and related anticonvulsants may induce life-threatening leukopenia,
      thrombocytopenia, and anemia in dogs. Phenobarbital-induced neutropenia in these
      3 dogs may have posed a risk for developing bacteremia. It is important for
      clinicians to be aware of adverse effects so that adequate precautions can be
      taken. A baseline hemogram should always be obtained before starting
      anticonvulsant treatment, and periodic hemograms should be obtained to monitor
      animals. Furthermore, client education should include instructions on recognizing
      signs of bacteremia, thrombocytopenia, and anemia.

PMID- 9524641
TI  - Use of an inactivated virus vaccine to control polyomavirus outbreaks in nine
      flocks of psittacine birds.
AB  - Nine flocks of psittacine birds were examined because of sudden death of
      neonates. In each flock, cause of death was determined to be polyomavirus
      infection, by means of DNA testing and in situ hybridization. Contaminated areas
      of aviaries were cleaned and disinfected, and vaccination programs, using a
      recently approved inactivated polyomavirus vaccine, were instituted. Use of the
      vaccine was found to be safe and efficacious.

PMID- 9524642
TI  - Metabolic responses of chronically starved horses to refeeding with three
      isoenergetic diets.
AB  - OBJECTIVE: To examine metabolic responses of chronically starved horses to
      refeeding with 3 isoenergetic diets. DESIGN: Uncontrolled clinical trial.
      ANIMALS: 22 mature mixed-breed horses that were emaciated but otherwise
      clinically normal. PROCEDURE: Horses were fed 1 of 3 diets: alfalfa hay, oat hay,
      or a combination diet of half oat hay and half commercially prepared ration.
      Digestible energy of diets was gradually increased throughout the refeeding
      period. One pre- and 4 postprandial blood samples were obtained daily, and
      analyses included RBC count, Hct, and determination of hemoglobin, glucose,
      insulin, free fatty acid, total bilirubin, 2,3-diphosphoglyceric acid,
      phosphorus, magnesium, calcium, sodium, and potassium concentrations. Body
      weight, fecal output, and feed and water consumption were measured and recorded
      daily. Repeated-measures ANOVA was used to examine dietary and temporal (day)
      effects of the 3 dietary regimens during 10-day trials. RESULTS: 19 Horses
      survived. Three horses (2 fed alfalfa diet, 1 fed combination diet) died of
      metabolic or gastrointestinal problems. Increasing temporal effects in serum
      concentrations of glucose, insulin, magnesium, calcium, and sodium; decreasing
      temporal effects in serum concentrations of free fatty acid, 2,3
      diphosphoglyceric acid, and phosphorus; and dietary effects in serum
      concentrations of glucose, insulin, magnesium, and potassium were detected in the
      19 surviving horses. Serum phosphorus and free fatty acid concentrations
      decreased dramatically during the first 5 days of refeeding with all 3 diets.
      Serum magnesium concentrations increased in horses fed the alfalfa hay diet,
      whereas improvement was not evident in horses fed oat hay or combination diets.
      Horses receiving the alfalfa and oat hay diets had lower postprandial glucose and
      insulin concentrations than horses receiving the combination diet. Horses fed oat
      hay alone ate 92% of feed offered, compared with 98% feed consumption for horses
      fed alfalfa hay or combination diets. CLINICAL IMPLICATIONS: Clinically normal
      emaciated horses can be successfully rehabilitated by gradual refeeding with a
      high forage diet.

PMID- 9524643
TI  - Congenital defects in newborn foals of mares treated for equine protozoal
      myeloencephalitis during pregnancy.
AB  - Three weak, recumbent neonatal foals with skin lesions, including a thin wooly
      coat, were born to mares being treated for equine protozoal myeloencephalitis.
      Mares received sulfadiazine or sulfamethoxazole-trimethoprim, pyrimethamine,
      folic acid, and vitamin E orally. Foals were anemic, leukopenic, azotemic,
      hyponatremic, and hyperkalemic. Serum folate concentrations in the 3 foals and 2
      mares were lower than those reported in the literature for clinically normal
      brood mares. Treatment was unsuccessful. For each foal, necropsy revealed
      lobulated kidneys with thin cortices and a pale medulla, and the spleen and
      thymus were small. Histologic examination revealed marked epidermal necrosis
      without inflammatory cells, thin renal cortices, renal tubular nephrosis,
      lymphoid aplasia, and bone marrow aplasia and hypoplasia. These observations
      indicate that oral administration of sulfonamides, 2,4-diaminopyrimidines
      (pyrimethamine with or without trimethoprim), and folic acid to mares during
      pregnancy is related to congenital defects in newborn foals.

PMID- 9524644
TI  - Evaluation of prostaglandin F2 alpha treatment in dairy cows at risk for low
      fertility after parturition.
AB  - OBJECTIVE: To evaluate the effect of 2 postpartum prostaglandin F2 alpha (PGF 2
      alpha) treatment protocols on reproductive performance of dairy cows at risk for
      low fertility. In addition, various medical conditions in cows that are
      recognized as having adverse effects on fertility were evaluated as criteria for
      fertility treatment. DESIGN: Prospective study. ANIMALS: 291 cows with, and 271
      cows without, risk factors for low fertility. PROCEDURE: Cows at risk for low
      fertility were randomly assigned to 2 treatment groups. Group-1 cows received 3
      i.m. injections of PGF2 alpha at weekly intervals after parturition, and group-2
      cows received 1 i.m. injection of PGF2 alpha 17 to 24 days after parturition.
      RESULTS: Compared with a single PGF2 alpha treatment 17 to 24 days after
      parturition, there was no added benefit of 3 treatments with PGF2 alpha 3 to 10,
      10 to 17, and 17 to 24 days after parturition in cows at risk for low fertility.
      Cows without risk factors for low fertility had 20% higher pregnancy rates,
      compared with cows with risk factors for low fertility. Twinning had a negative
      effect on future fertility. CLINICAL IMPLICATIONS: Results of this study indicate
      that further consideration should be given to the timing and intervals of PGF2
      alpha administration after parturition. Risk factors for low fertility, such as
      retained placenta, twins, and assisted calvings, are valid criteria to evaluate
      different treatment options to improve fertility in dairy cows.

PMID- 9524645
TI  - Brucellosis in adult beef cattle of Mexican origin shipped direct-to-slaughter
      into Texas.
AB  - OBJECTIVE: To compare prevalence estimates of brucellosis (BR) in adult beef
      cattle that originated from different states and regions of Mexico and that were
      shipped direct-to-slaughter into Texas during 1995. DESIGN: Epidemiologic survey.
      ANIMALS: About 65,000 adult beef cattle. PROCEDURE: Blood samples were collected
      during postmortem examinations and were tested for serum antibodies to Brucella
      abortus, using the particle concentration fluorescence immunoassay and automated
      complement-fixation test. Prevalence estimates and 95% confidence intervals of BR
      were calculated by state of origin in Mexico. The difference among prevalence
      estimates of BR in cattle from different states and regions was tested for
      significance (P < 0.05), using the proportion test. RESULTS: On the basis of
      serologic test results, the overall prevalence estimate of BR was 0.32%. The
      prevalence estimate of BR in cattle from the state of Chihuahua (0.10%) was
      significantly different than that in cattle from the states of Nuevo Leon
      (0.23%), Zacatecas (0.34%), Durango (0.47%), Chiapas (1.81%), Tamaulipas (2.71%),
      Aguascalientes (7.89%), and Campeche (12.24%). In addition, prevalence estimates
      of BR in cattle were significantly different among the northern (0.22%), south
      central (3.18%), and south coastal (9.42%) regions of Mexico. CLINICAL
      IMPLICATIONS: Results of this study indicate that the number of cattle exposed to
      B abortus may be significantly different among states and regions of Mexico.
      Current import sanitary requirements should continue to mitigate potential risk
      of transmission of BR from sexually intact cattle of Mexican origin to Texas
      cattle.

PMID- 9524646
TI  - Acute nonfatal erysipelas in sows in a commercial farrow-to-finish operation.
AB  - Acute nonfatal erysipelas was diagnosed in 4 sows in a 1,000-sow commercial
      farrow-to-finish operation in Indiana. Sows were pyrexic, lethargic, lame, and
      had multiple, 1.3- to 7.6-cm, erythematous rhomboid skin lesions. Outbreak was
      attributed to failure to properly vaccinate pigs. Further morbidity and mortality
      were prevented by treatment of clinically affected sows and all pigs in close
      proximity with procaine penicillin G daily for 3 consecutive days and vaccination
      of all pigs with questionable vaccination status, using bacterin of killed
      Erysipelothrix rhusiopathiae. Periodic review of herd management protocols is
      important to ensure that recommended vaccination schedules are being followed and
      animals are receiving quality vaccinations. Human error can contribute to many
      production problems and should be included on the differential diagnoses list.

PMID- 9524647
TI  - Urinary obstruction in a hermaphroditic llama.
AB  - A 24-hour-old cria was admitted for evaluation of stranguria evident shortly
      after birth. On physical examination, the prepuce appeared to be normally formed
      and small drops of fluid dripped from it as the cria strained to urinate. Testes
      could not be palpated. Ultrasonographic examination revealed that the bladder was
      distended. The only abnormality detected on serum biochemical analysis was high
      creatinine concentration. Tube cystostomy was performed, and the cria was treated
      with saline (0.9% NaCl) solution administered intravenously and antibiotics. Four
      days after admission, the cria could not urinate normally when the cystostomy
      tube was occluded. Five days after admission, normograde cystography and
      retrograde urethrography were performed. Radiographic findings indicated the cria
      was an intersex llama with urethral duplication. The llama was euthanatized at
      the owner's request. Necropsy revealed bilateral ovotestes with a phenotypically
      female reproductive tract and urethral duplication. Urethral duplication should
      be considered as a cause of stranguria in male neonatal crias, and
      hermaphroditism should be included as a cause of urethropathies in llamas.

PMID- 9524649
TI  - Studies on use of homeopathy in animals.

PMID- 9524648
TI  - Epidemiologic analysis of reported scrapie in sheep in the United States: 1,117
      cases (1947-1992)
AB  - OBJECTIVE: To determine epidemiologic features associated with reported cases of
      scrapie in sheep in the United States. DESIGN: Retrospective study. SAMPLE
      POPULATION: Records for scrapie-positive sheep flocks and sheep with clinical
      signs consistent with scrapie reported to the USDA from 1947 through 1992.
      PROCEDURE: Records from the USDA's scrapie control and eradication program were
      abstracted, entered into a computer database, and statistically analyzed.
      RESULTS: 1,117 sheep from 657 flocks located in 39 states were scrapie positive
      during the study period. Seasonal or spatial trends were not evident. Mean yearly
      proportion of scrapie-positive flocks increased slightly from 1965 through 1992.
      One hundred sixty-eight rams and 949 ewes were reported to be scrapie positive
      during the study period, which was slightly more rams than expected if the
      disease was equally likely to affect rams and ewes. Suffolks (972/1,117; 87%) and
      Hampshires (68/1,117; 6%) were most commonly affected. CLINICAL IMPLICATIONS: The
      prevalence of scrapie in sheep in the United States is unknown. Bias in this
      study may have resulted from inconsistencies in available information,
      misclassification of sheep with clinically suspicious signs of scrapie, and
      changes in the national scrapie control and eradication program that likely
      affected willingness of owners and veterinarians to report potentially infected
      sheep.

PMID- 9524650
TI  - [Surgery and the surgeon today].

PMID- 9524651
TI  - [HIV cladistics: or about the branches of the olive tree of helplessness in
      knowledge].

PMID- 9524652
TI  - [Apoptosis].

PMID- 9524653
TI  - [Nitric oxide as a neuronal messenger].

PMID- 9524654
TI  - [The current and future outlook in immunosuppressive therapy for children].
AB  - The various cell proportions that form the immune system intervene in the
      activation of autoreactive cells and in the occurrence of the associated
      inflammatory process. Advances of the study of the mechanism involved in the
      autoimmunity, and the development of new immunosuppressive agents used for
      transplantations have deeply modified the therapeutic approaches. The classic
      treatment of autoimmune diseases has relied on corticosteroids and
      immunosuppressive drugs. Now, these new treatments are evaluated on animal
      models, then controlled in clinical trials. Cyclosporin A has been shown to be
      effective in several autoimmune diseases. Intravenous immunoglobulins, cytokines,
      and anticytokines, immunotoxins, monoclonal anti-leukocyte antibodies (CD4, CD25)
      and soon peptide vaccination constitute the new types of treatments.

PMID- 9524655
TI  - [The neurohormonal mechanisms involved in the etiopathogenesis of arterial
      hypertension in pregnancy].

PMID- 9524656
TI  - [An update on the therapy of tuberculous meningitis].

PMID- 9524657
TI  - [Retrograde cholangiopancreatography (ERCP) and endoscopic sphincteropapillotomy
      (ES) in the diagnosis and treatment of common bile duct (CBD) lithiasis].
AB  - The common bile duct (CBD) stones often gives real difficulties of diagnosis and
      treatment. The ultrasound (US) does not offer in a significant percentage of
      cases certain diagnostic data, and the unconventional imaging techniques such as
      computer tomography (CT) are yet less accessible. ERCP appeared in the last
      period as an optional method for the diagnosis of common bile duct stones, and,
      moreover, permitted the development of the nonsurgical treatment possibilities.
      ES and the extraction of stones revealed in this frame as preferable, especially
      in the high surgical risk cases. This study presents the results of ERCP
      performed in 547 and the therapeutic value of ES in 284 cases with CBD stones
      (conclusions of the ERCP and ES used in the clinical practice, in our clinic, in
      the last three years). In 81.69% cases ES managed the dezobstruction of the CBD,
      with a frequency of complications of 4.33% and a related mortality rate of 0.78%.

PMID- 9524658
TI  - [The role of physical training in lipid metabolic parameters in patients with
      chronic myocardial infarct].
AB  - OBJECTIVES: The aim of the study is to follow the variation of some parameters of
      the lipidic metabolism, during physical training, at patients with chronic
      myocardial infarction. METHODS: Among 132 patients with chronic myocardial
      infarction, we selected 22 patients, mean age 47.4 +/- 6.08 years from which 18
      followed supervised physical training a period of 3-6 months. There were
      determined before and at the end of the interval, the following parameters: serum
      lipids, serum cholesterol, HDLcol, LDLcol, triglicerids, apolipoproteins A,B, Apo
      B/A ratio. The statistical comparison has been made for each parameters, by
      univariate and multivariate analysis. RESULTS: HDLcol increased significantly in
      the study group at the end of the interval (from 28.9 mg% to 42.3 mg%, p <
      0.001); LDLcol and total cholesterol did not vary. Apo A increased significantly,
      but Apo B/A ratio did not change. CONCLUSIONS: Physical training altered the
      lipidic profile by increasing the protective fraction of the cholesterol--HDLcol
      and Apo A.

PMID- 9524659
TI  - [Thyroid cancers].
AB  - We have analysed factors that influenced on the patient survival in 195 cases of
      thyroid cancer. The survival is essentially influenced by the histology, the
      papillary forms (survival after 15 years: 83.1-93%) and follicular cancers
      (survival after 15 years: 84-94%) having an excellent evolution. The non
      differentiated and mixed cancers have a very severe prognosis that is independent
      of the complex therapy that have been used (survival after 5 years: 17.1% in non
      differentiated forms and 32.5% in mixed ones). The prognosis is better in
      subjects under the age of 45 and in female subjects. The cancers in the 1-st and
      2-nd stage of tumor extension have a better evolution that those in the 3-rd
      stage. In differentiated cancers, the total or subtotal thyroidectomy followed by
      radioiodine administration determine the best survival.

PMID- 9524660
TI  - Experimental and clinical correlation in acute pancreatitis pathogenesis.
AB  - Pathological aspects in 100 cases of operated A.P. different in severity are not
      strictly related to aetiological conditions. Clinical observations have suggested
      some components of pathogenesis: obstruction of bilio-pancreatic inflow in
      duodenum at the beginning of the attack, bilio-pancreatic reflux on
      cholangiograms, strong secretory digestive stimulation before attack. Some
      experimental animals models (dogs) which can mimic pathogenic mechanism
      (obstruction of pancreatic flow, common bilio-pancreatic duct, closed duodenal
      loop, acute cholecystitis) have revealed characteristic pathological changes
      depending on the initiating process. Our conclusion that severity of pathological
      changes in A.P. are determined by the initiating mechanisms which may differ in
      some aetiological condition or may be common for different ones.

PMID- 9524661
TI  - [Malignant tumors of the digestive tract below the diaphragm in young people].
AB  - We have retrospectively studied 1243 malignancies of the infradiaphragmatic tract
      treated in the First Surgical Clinic between 1978-1994 (678 gastric, 300 rectal
      and 256 colonic malignancies). Out of these 39 cases have been encountered in
      young patients (14 gastric, 13 colon and 12 rectal malignancies). The following
      particularities have been noted in this group: hereditary predisposition, more
      advanced stage at diagnosis, predominance of non-Hodgkin lymphomas and poorly
      differentiated forms. Young age does not significantly influence prognostic, with
      the control group. In young people the most important prognostic factors are
      tumor stage, cellular grading and tumor DNA index as determined by flow
      cytometry.

PMID- 9524662
TI  - [Nonobstructive intestinal ischemia].
AB  - Acute or chronic intestinal ischaemia can be the consequence of either intrinsic
      vascular disease, systemic disease, drugs or surgical procedures. In one quarter
      of the patients with intestinal ischemia, no major vascular obstructions can be
      detected. Very rarely, the cause of ischaemia is splanchnic vasoconstriction due
      to cardiac arrhythmias or sepsis. The bowel becomes ischaemic as a result of
      underperfusion. The clinical picture resembles the one of occlusive intestinal
      ischaemia. From the pathological standpoint, the ischaemia is more intense on the
      antimesenteric border of the bowel and the lesions are more advanced in the
      mucosal than in the serosal layer. Often, the ischaemia involves other organs
      too: liver, spleen or gallbladder. The reconstructive vascular procedures are
      inefficient, the only therapeutical options remains the resection of the
      infarcted bowel, together with other organs involved in the ischaemic process.
      The mortality rate approaches 90%.

PMID- 9524663
TI  - [Radiotherapy concomitant with cisplatin chemotherapy in the treatment of cancer
      of the cervix uteri].
AB  - Cancer of the cervix presents an increasing incidence and mortality in advanced
      stages. Failure of treatment consists in local recurrence, continuation of
      evolution or in distant metastasis. One of the strategies of improving the
      treatment response is the association of radiosensitization chemotherapy with
      irradiation. The aim of this paper is the study of the effect of cisplatin
      administration simultaneously with radiotherapy of primary cancer of the cervix
      and recurrences. This association has proved to be favourable as regards
      immediate and short period local control with an acceptable digestive and
      hematologic tolerance (gr. I-II).

PMID- 9524664
TI  - [The treatment of giant-cell tumors of the lower extremity of the radius by
      resection-reconstruction].
AB  - The location of the mega-cell tumours in the inferior extremity of radius is
      relatively frequent and it represents 10 percent from all mega-cell tumours. The
      aggressive tumours and the relapsed one must be cut-away. In 3 of the cases which
      were operated, after a large cutting of the tumour, the author used for
      reconstruction a grafting from the fibula-bone without vascularisation. The
      fixing of the focus metallic plates is highly superior to other osteosynthesis.
      After 3 years, now relapse was remarked. The functional results can be considered
      good-enough, even some of patients can not perform hard-working.

PMID- 9524665
TI  - [The endoscopic sclerotherapy of esophageal varices in children].
AB  - The injection sclerotherapy of esophageal varices is an important path in the
      treatment of acute bleeding. This procedure is carried out either in emergency
      conditions concerning bleeding varices or in the chronic status, the sclerotic
      drug being injected into and round the dilated infraesophageal veins. This study
      shows the authors' experience beginning with 1992; since then, at Children's
      Hospital of Iasi the injection sclerotherapy has become an usual method in the
      management of the oesophageal varices, especially in the chronic status. This
      method turns out to be very useful, because nu matter the etiology would be,
      allows the postponement of decompressive procedures until the child has a proper
      age.

PMID- 9524666
TI  - Flow-cytometry DNA index of colorectal carcinomas.
AB  - The authors investigated the relationship between flow cytometric DNA index (D.I.
      defined as the ratio of the DNA content of malignant cells to that of normal
      cells) and other prognostic factors (grade, stage of the disease, anatomical
      site, patients' sex and age) of 20 patients with colorectal cancer. The entire
      material was obtained from 20 unselected and previously untreated patients. This
      material consists of fresh tumoural or normal tissues taken after radical
      colectomy for the flow-cytometric analysis. A normal diploid DNA content was
      found in six tumours, the other fourteen being founded to be aneuploid. All non
      malignant tissue samples showed normal diploid DNA content. In the current series
      of cases we have found that DI was significantly associated with stage but not
      with grade, anatomical site or other prognostic factors. Our data indicates that
      cytometrically evaluated DI values have probably an independent predictive power
      for the clinical outcome of colorectal cancer patients.

PMID- 9524667
TI  - [An in-vitro study of 99mTc sestamibi uptake by normal and neoplastic cell
      lines].
AB  - The hexakis (2-methoxy isobutyl isonitrile) technetium (I) (99mTc MIBI) is a
      representative molecule for a class of monocationic lipophile 99mTc compounds,
      knowing to be initially used like myocardial scintigraphic agents, and now also
      in oncological scintigraphy. This present study aims to compare the in vitro
      99mTc MIBI cellular uptake on some normal and neoplastic cells. Three tumoral
      cell lines were used: M4Beu (pigmented melanoma), M3Dau (pigmented melanoma),
      MCF7 (breast cancer), in comparison with newborn rat cardiac myocytes and
      fibroblasts. Monolayers cultures cell were incubated for 1 hour with 37 kBq of
      99mTc MIBI. Our results: (a) confirm a preferentially 99mTc MIBI uptake on the
      myocytes in comparison of the fibroblasts; (b) show that this uptake is very
      different on the neoplastic studied cultures cells, depending on the cell type
      (higher on M3Dau in comparison of the other two malignant cell lines, and also
      higher than the myocytes. The neoplastic cellular mechanisms to accumulate 99mTc
      MIBI, are only hypothetically understand; there are thought to be also in
      relation with the Nernst equations, applied at the plasmatic and mitochondrial
      membranes level, like in normal cells. A correlation with some phenotypic
      neoplastic cells characteristics, in relation with the malignancy tumoral
      potential seems possible. If there is the case, this can be a possible
      explanation of some in vivo imaging results, obtained with 99mTc MIBI, in
      oncologic scintigraphy.

PMID- 9524668
TI  - [The isolation and subtyping of the human immunodeficiency virus (HIV) from
      children in Moldova. The evidence for subtype F].
AB  - HIV epidemic related to nosocomial transmission in Romanian nursed children
      represents up to now more than 50% of paediatric AIDS cases in Europe. Although
      the sources of this epidemic are obscure, HIV-1 subtype F, a minor form in Brasil
      and Africa, realised a founder effect in this risk group, thus becoming the major
      form in Romanian epidemic. This study presents the results of the virus isolation
      from HIV-infected children in Northeast Romania. Heteroduplex mobility assay
      (HMA) was performed in order to establish HIV-1 viral subtype for 6 isolates. All
      tested HIV-1 strains were proved to belong to F subtype. So, our study confirm
      that HIV-1 subtype F is responsible for the epidemic in the risk group of
      Romanian nosocomially infected children.

PMID- 9524669
TI  - [The determination of the prevalence of antibodies to the hepatitis C virus (anti
      HCV) and of the serum levels of C-reactive protein in chronic dialysis patients].
AB  - The chronic dialysis patients are subject at risk for the hepatitis C virus (HCV)
      infection. Among these subjects, the hemodialysis-induced and increased synthesis
      of IL6 which suggest an acute phase response. 58 chronic dialysis patients were
      tested for presence of anti-HCV antibodies; 45 (77.58%) presented this
      serological marker. None of the 15 nursing subjects tested presented anti-HCV. C
      reactive protein (CRP) levels were measured in 41 patients. Elevated levels were
      detected in 5 (12.19%) patients. Such a high prevalence of anti-HCV reveals the
      hemodialysis to be a risk factor for the HCV infection. CRP levels measured by
      Mancini method lack the sensitivity for a more accurate interpretation.
      CONCLUSION: 1. the high anti-HCV prevalence among hemodialysis patients emphasize
      the opportunity of blood testing also for serological markers in ante
      transfusional screening. 2. the immunoturbidimetry method for CRP testing may be
      a better assay in order to establish significant correlations.

PMID- 9524670
TI  - [The frequency of Streptococcus anginosus in the pharyngeal exudate from children
      and its differentiation from other beta-hemolytic streptococci].
AB  - S. anginosus is a commensal of the oro-pharyngeal mucous membrane without any
      signification for the local pathology. Ignoring the existence of beta-haemolytic
      colonies of this species, the risk to report the presence of some beta-haemolytic
      streptococci that actually belong to the normal flora exists. The antigenic
      identifications of beta-haemolytic streptococci maintain the confusion either, S.
      anginosus being able to react with specific sera anti group G, C or A. In our
      study, two identification criteria out of those available demonstrated a high
      value: the small or very small colonies' size, especially in secondary cultures
      and the production of acetoin (Voges-Proskauer test). S. anginosus was isolated
      with a quite great frequency in pharyngeal exudate from children: 41 strains out
      of 90 strains of beta-haemolytic non-group A streptococci were S. anginosus.
      Antigenically they belonged, in numerical order to groups C, G, F or they were
      ungroupable. IN CONCLUSION: The microbiologist has to identify, but not to report
      the presence of S. anginosus in pharyngeal exudate, it being a normal component
      of the oro-pharyngeal flora. Doing so, a better evaluation of the clinical
      signification of the other beta haemolytic streptococci's non group A will be
      possible.

PMID- 9524671
TI  - Enrichment medium for isolation of Campylobacter jejuni-Campylobacter coli.
AB  - A kaseini-broth enrichment medium (KBEM) for the isolation improvement of
      Campylobacter jejuni-Campylobacter coli from stool samples is described.
      Isolation of Campylobacters from stool specimens by direct inoculation onto solid
      selective medium was compared with isolation after twenty-four hours enrichment
      at 37 degrees C in KBEM, followed by subculture onto the same solid selective
      medium. Of 156 examined stool samples from diarrhoeal children positive results
      were obtained from 17 patients altogether: 11 by direct inoculation on selective
      media and 6 only owing to enrichment. Thus, an increase of 35.3% in the isolation
      rate was obtained by using the enrichment medium. The same medium allows the
      preservation of isolates of Campylobacter jejuni-Campylobacter coli for 2 months
      and longer at 37 degrees C.

PMID- 9524673
TI  - [Therapy with large doses of methylprednisolone in Basedow's ophthalmopathy].
AB  - Up to now there is no satisfactory therapeutical method in Graves' ophthalmopathy
      (GO). Recently, several authors have published the results of the so-called
      "pulse" method of corticotherapy, using intravenous methylprednisolone (MP) 1 g
      dissolved in 200 ml isotonic NaCl solution. We have treated with this method 4
      patients (3 women and 1 man, aged between 35-62 years) with severe GO (III-V
      class after AMT Classification). Although the number of perfusions varied between
      1 (2 patients) and 8, the results are encouraging: 3 improvements, 1 stationary
      evolution (after a single "pulse"). We have not noticed important side-effects.
      In conclusion we consider that the "pulse" method have proved its efficiency,
      recommendable in severe GO.

PMID- 9524672
TI  - [The value of C-reactive protein for the differentiation of bacterial meningitis
      from viral meningitis].
AB  - In order to differentiate bacterial meningitis versus viral meningitis, we have
      comparatively tested the efficacy of the following tests: C-reactive protein
      (CRP), erythrocytes sedimentation rate (ESR), fever, level of glucose in cerebro
      spinal fluid (CSF), glucose in CSF/glycemia ratio, number of white blood cells in
      peripheric blood, percentage of neutrophils in peripheric blood, level of
      proteins in CSF and number of nucleated cells in CSF for a group of 49 patients,
      both children and adults with central nervous system infection (37 patients with
      bacterial meningitis and 12 with viral meningitis) hospitalised between May 1993
      and July 1994 in Clinical Hospital for Infectious Diseases in Iasi. The mean
      value of CRP in bacterial meningitis patients was 8.78 mg%, contrasting with the
      mean value of CRP = 1.92 mg% recorded in patients with viral meningitis. Ten out
      of 37 bacterial meningitis patients presented a CRP concentration < 1.85 mg%. All
      these 10 patients have already had an antibiotic treatment at the moment of the
      assay. One out of 12 cases of viral meningitis had a value of CRP = 3.3 mg%, all
      the remainder cases having values under 1.85 mg%. We recorded highly significant
      differences between the two patient groups for CRP (p < 0.001), ESR (p < 0.01),
      protein concentration in CSF (p < 0.001) and number of nucleated cells in CSF (p
      < 0.001). Differences recorded for fever, concentration of glucose in CSF,
      glucose in CSF/glycemia ratio, number of leucocytes in peripheric blood and
      percentage of neutrophils in peripheric blood, were not significant (p > 0.5).
      Data were analysed also by box-plot method which facilitates the visual appraisal
      of the differences recorded between the two aetiological groups. In conclusion,
      assays of CRP and ESR may be used as differentiation tests for bacterial
      meningitis versus viral meningitis, when assay is done before the antibiotic
      treatment, being sufficient sensitive, and easy to perform.

PMID- 9524674
TI  - Effect of the EGb 761 (Ginkgo bilboa extract) on primary immune response in
      experimental chronic stress.
AB  - The effect of a chronic stress upon the primary immune response on mice was
      evaluated by using the plaque-forming cells (PFC)-direct technique, which allowed
      us to record a serious suppression of the immune response in the exposed animals.
      In the next phase of the experiment a second group was initially treated with
      Tanakan (EGb 761--Ginkgo biloba extract) and then it was submitted to the same
      chronic stress: this procedure did not bring about the increase of the number of
      lymphocytes but it significantly improved the function of these cells.

PMID- 9524675
TI  - [The lipid peroxidation process in depression: the effect of trazodone].
AB  - We investigated the lipid peroxidation in depression by determining the markers
      of this process: melondialdehide, total SH groups and catalase. We used blood
      samples from inpatients with specific psychiatric symptoms. The medication
      consist of hypnotic nitrazepam and antidepressant trazodone, using film-coated
      tablets trazolon, 50 mg once a day, three weeks. In the second part of our
      experiment, we studied the antioxidant properties of trazodone, using blood
      samples from healthy subjects. It remain to establish if the free radicals are
      responsible for the initiation of depression or not.

PMID- 9524676
TI  - [The synthesis and biological activity of new disubstituted carbanion ylides from
      pyridazine].
AB  - Continuing the investigations in view obtaining new carbon-nitrogen stable
      dissiniu-ilydes, were obtained new 3-phenyle-pyridaziniu-ylides carbanion
      disubstituted. The antimicrobial and antifungus action of the products VIa, VIb,
      VIIa, VIIb and VIIc also studied.

PMID- 9524677
TI  - [Occlusal rehabilitation under conditions of the simulation of averages].
AB  - The Fag articulator is an anatomical and semi-adaptable one, light and with a
      supple, stable and rigid mechanism of manipulation and an easy access to the
      models. These characteristics make it more sensitive in all situations of
      occlusal rehabilitation. The articular system permits the exactness mechanical
      reproduction of the fundamental movements of the mandible, with the possibility
      to reproduce the characteristics of the lateral movements (angle Benett
      adjustable), protrusion and variable inclinations of the condylar slope. The
      employment of this articulator in the dentistry practice allowed us to obtain a
      functional occlusal rehabilitation in all types of edentulous and we avoided the
      premature occlusal contacts.

PMID- 9524678
TI  - [Kartagener's syndrome--the ciliary dyskinesia syndrome].

PMID- 9524679
TI  - [The role of the experiment in evaluating psychotropic substances].
AB  - Designing new experimental models on animals for testing psychotropic drugs
      encounter important difficulties. The criteria for choosing a certain model, some
      pharmacokinetic aspects and few examples of models used in psychotropic drug
      testing are briefly presented.

PMID- 9524685
TI  - [Spirituality and material reality in medical education in Iasi].

PMID- 9524686
TI  - [Centenary of the birth of Prof. Vladimir Butureanu, a famous personality of the
      Iasi School of Surgery].

PMID- 9524687
TI  - [XXVI Maghrebin Medical Conference. Tunis, 19-21 May 1997. Abstracts].

PMID- 9524688
TI  - 2nd African Congress of Rheumatology. Tunis, October 15-18, 1995. Abstracts.

PMID- 9524689
TI  - Biophysical Society 42nd annual meeting. Kansas City, Missouri, USA. 22-26
      February 1998. Abstracts.

PMID- 9524690
TI  - 23rd World Congress of the International Society for Cardiovascular Surgery.
      London, United Kingdom, September 21-26, 1997. Abstracts.

PMID- 9524691
TI  - British Paediatric Neurology Association annual meeting 1998. Abstracts.

PMID- 9524692
TI  - Annual meeting of the Society for Adolescent Medicine. March 1998. Abstracts.

PMID- 9524693
TI  - Cumulative index, volumes 21-30 (1988-97).

PMID- 9524695
TI  - Cumulative index volumes 1-20, 1978-1997.

PMID- 9524696
TI  - [French Society of Orthopedic Surgery and Traumatology membership list].

PMID- 9524694
TI  - The Physiological Society proceedings of the scientific meeting held at UMDS (St
      Thomas's), London, 6-8 November 1997.

PMID- 9524697
TI  - [72nd annual meeting of the French Society of Orthopedic Surgery and
      Traumatology. Abstracts].

PMID- 9524698
TI  - Swedish Association of Urology annual meeting. Stockholm, Sweden, November 27-28,
      1997. Abstracts.

PMID- 9524700
TI  - Indications for axillary dissection in T1 breast cancer.
AB  - BACKGROUND: Debate regarding axillary dissection in the treatment of women with
      small invasive cancers of the breast has been increasing. Recently, omission of
      axillary dissection has been proposed because of the reported low incidence of
      nodal metastases in women with such cancers. Variation in the incidence of nodal
      metastases in T1 breast cancers is examined and discussed with regard to a
      selective approach to lymphadenectomy. METHODS: The literature was reviewed, and
      cases of 2185 women with T1 breast cancers in Rhode Island and Massachusetts were
      analyzed. RESULTS: The incidence of axillary nodal metastases in T1 breast cancer
      varies among series and ranges from 3% to 37%. The probability of nodal
      metastases depends on tumor grade and patient age as well as tumor size.
      CONCLUSIONS: T1 breast cancers are not equivalent in their risk of associated
      axillary metastases. A treatment algorithm for selective axillary node dissection
      in patients with T1 breast cancers is proposed. Future applications of this type
      of algorithm are discussed with respect to sentinel node biopsy.

PMID- 9524699
TI  - IOHDR brachytherapy in recurrent or metastatic colorectal carcinoma.

PMID- 9524701
TI  - Role of chest CT in patients with negative chest x-rays referred for hepatic
      colorectal metastases.
AB  - BACKGROUND: Hepatic resection is the standard treatment for hepatic colorectal
      metastases. The lung represents the next most likely site, after the liver, of
      metastatic disease. Computed tomography (CT) of the chest is more sensitive than
      is chest x-ray in detecting metastatic lung lesions. However, the usefulness of
      chest CT in the evaluation of patients before hepatic resection remains
      uncertain. METHODS: One hundred consecutive patients with negative chest x-rays
      and potentially resectable hepatic colorectal metastases underwent chest CT.
      Patients with CT findings suggestive of metastatic disease were subjected to
      thoracotomy or video-assisted thoracic surgery (VATS) before laparotomy and
      attempted hepatic resection. The operative findings and clinical course were
      analyzed. RESULTS: Eleven of 100 patients had a positive chest CT. Four of these
      11 patients had malignant lesions of the lung (three metastatic colorectal
      cancers and one primary lung cancer). There was no difference in median total
      hospital stay (8.5 days [range 7 to 13 days] vs. 8.0 days [range 3 to 49 days]),
      number of perioperative deaths (0 vs. 2 deaths), or long-term outcome between
      those patients with a positive chest CT undergoing thoracotomy/VATS and those
      patients with a negative chest CT. Overall, chest CT provided a positive yield of
      4% and a positive predictive value of 36% for the detection of malignant lesions
      of the lung. CONCLUSIONS: Chest CT only minimally improved detection of malignant
      lesions of the lung over chest x-ray. Thoracotomy/VATS and wedge resection of
      lung nodules did not adversely affect outcome. The low positive yield and low
      positive predictive value of chest CT in the setting of a negative chest x-ray
      places in question the usefulness of routinely performing chest CT as part of the
      extent-of-disease work-up before hepatic resection.

PMID- 9524702
TI  - Intraoperative high dose rate brachytherapy in recurrent or metastatic colorectal
      carcinoma.
AB  - BACKGROUND: The survival of patients with recurrent or metastatic colorectal
      cancer usually is less than 12 months. In an attempt to improve this dismal
      prognosis, we investigated the role of intraoperative high dose rate
      brachytherapy (IOHDR) in the management of these patients. METHODS: From April
      1992 to December 1996, 26 patients with locally recurrent or metastatic
      colorectal carcinoma were treated with maximal surgical resection and IOHDR.
      Intraoperative radiation dose ranged from 10 to 20 Gy, prescribed at 0.5 cm
      depth. The residual tumor irradiated was microscopic in 16 patients (62%) and
      gross residual in 10 patients (38%). Six patients received postoperative external
      beam radiation therapy. RESULTS: After a median follow-up of 28 months (range 6
      to 54 months), seven of 15 evaluable patients (47%) failed in the area treated
      with IOHDR. The median time to local failure was 21 months (range 4 to 52
      months). The median survival was 23 months (microscopic 24 months; gross 17
      months), with a 4-year actuarial survival rate of 36%. Major morbidity was
      observed in 7 patients (47%) and usually was surgery-related. CONCLUSION: The use
      of IOHDR in association with radical resection increases local control in
      patients with recurrent or metastatic colorectal cancer. Patients with
      microscopic residual disease achieved a better result than do those with gross
      residual disease. Future strategies include the addition of limited EBRT dose to
      IOHDR, even for previously irradiated patients.

PMID- 9524703
TI  - Incidence of axillary lymph node metastases in T1a and T1b breast carcinoma.
AB  - BACKGROUND: We investigated the incidence of axillary lymph node metastases in
      patients with T1a (< or = 0.5 cm) and T1b (> 0.5 cm and < or = 1.0 cm) breast
      cancers. METHODS: The charts of 2000 patients who underwent axillary lymph node
      dissection for breast cancer at our institution from 1989 to 1991 were reviewed.
      Of these, 81 patients had T1a and 166 had T1b primary breast cancers. RESULTS:
      Among the 247 patients with T1a and T1b breast cancers, nodal metastases were
      present in 30 (12.1%), with a 7.4% positivity rate for patients with T1a and
      14.5% positivity rate for T1b tumors. Of the 212 patients who had > or = 10 nodes
      dissected, 29 (13.7%) had positive nodes. Of those, 6 of 60 (10.0%) patients with
      T1a and 23 of 152 (15.1%) with T1b tumors had positive nodes. The presence of
      lymphovascular invasion (LVI) predicted a significantly higher nodal positivity
      rate (27.8% vs. 10.9%, p = 0.05). CONCLUSIONS: Of patients with adequately
      evaluated axillae, 10% with T1a and 15% with T1b cancers were found to have nodal
      metastases. Although LVI was significantly associated with a higher risk of lymph
      node metastases, we could not characterize any subgroup at acceptably low risk of
      nodal positivity. Until a more useful prognostic indicator is discovered,
      axillary dissection should continue to be part of the mainstay of management for
      small breast cancers.

PMID- 9524704
TI  - Surgeon variability in treating nonpalpable breast cancer: surgical oncology as a
      value-added specialty.
AB  - BACKGROUND: Several studies have demonstrated a relatively low rate of breast
      conservation surgery (BCS) in the United States. Few have analyzed the impact of
      individual surgeon variability on the outcome of the procedure, and none have
      contrasted surgical oncologists versus general surgeons in the treatment of
      nonpalpable breast cancer. METHODS: A blinded review was done of 409 excisions
      for nonpalpable breast cancer performed by 11 board-certified general surgeons
      (GS, n = 221) and one surgical oncologist (SO, n = 185) in a teaching
      institution. We compared surgical margins, need for reexcision, and breast
      conservation rates. RESULTS: Although there were no significant differences in
      patient and tumor characteristics, there were surprising differences between the
      GS and SO, especially related to surgical margins and final treatment. The SO has
      a significantly higher rate of frozen section compared to GS (81% vs. 64%, P <
      0.01) and a lower rate of positive margin at the time of original biopsy (25% vs.
      41%, P < 0.01). These differences translated into lower necessity for reexcision
      of tumor (18% vs. 48%, P < 0.01) and higher rate of BCS (88% vs. 70%, P < 0.01).
      CONCLUSION: This study demonstrates marked differences among trained general
      surgeons. The additional experience of a surgical oncologist is valuable, because
      fewer positive margins lead to a higher likelihood of breast preservation and
      decreased costs related to fewer additional operative procedures.

PMID- 9524705
TI  - Current treatment for lobular carcinoma in situ.
AB  - BACKGROUND: We thought that observation for patients with lobular carcinoma in
      situ (LCIS) had been generally accepted by the mid-1980s. A questionnaire mailed
      to oncologic surgeons in 1988 revealed that 33% of the respondents still advised
      unilateral mastectomy, although a slim majority (54%) advised observation. New
      studies have been published in the intervening 8 years, and we decided it would
      be worth recirculating the 1988 questionnaire. METHODS: The identical
      questionnaire was mailed to members of the same oncologic societies (Society of
      Surgical Oncology [SSO] and Society for the Study of Breast Disease), but changes
      in membership necessitated new mailing lists. RESULTS: Observation has yet to be
      universally accepted by the oncologic community, but at this time 85% of the
      respondents suggest it as the preferred option for their patients. CONCLUSIONS:
      Recent studies have questioned some of the tenets laid down by Haagensen in 1978,
      but it appears clear that his formulation of LCIS as a marker of increased risk
      continues to gain ground over the original concept of inevitable progression to
      invasive disease.

PMID- 9524706
TI  - Multifocal extremity sarcoma: an uncommon and controversial entity.
AB  - BACKGROUND: The primary site of metastasis from extremity sarcomas is the lung.
      When patients with extremity sarcoma present with the disease in more than one
      site but not in the lung, the question of whether the disease is multifocal or
      metastatic is difficult to resolve. METHODS: We reviewed 1423 patients admitted
      with extremity sarcoma from 1982 through 1996. Patient demographics, primary
      site, other sites, local recurrence, distant metastasis, and survival were
      analyzed. Statistics were by Fischer exact test, chi 2, Kaplan-Meier method, and
      log-rank test where appropriate. RESULTS: Sixteen (1%) patients were identified
      with multifocal disease out of 1423 patients with extremity sarcoma. There was no
      difference in sex, age, size, grade, depth, and margins between multifocal and
      unifocal disease. In a mean follow-up time of 57 months, 50% had local recurrence
      of primary tumor, 80% had distant metastasis, and only 30% were alive at the time
      of the analysis. Whereas 21% of all patients with solitary disease develop lung
      metastasis, 63% of patients with apparent multifocal disease develop lung
      metastasis. The 5-year disease-specific survival of patients with multifocal
      disease was not different from that of all patients presenting with metastatic
      disease to lung. CONCLUSION: Whether multifocal disease exists or is merely a
      form of metastasis is unproven by this analysis, but the outcome is the same.
      Management algorithms should suggest treating patients with multifocal disease as
      if it is metastatic disease.

PMID- 9524707
TI  - Superficial extremity soft tissue sarcoma: an analysis of prognostic factors.
AB  - BACKGROUND: Experience with soft tissue sarcoma has suggested that superficial
      tumors have a favorable prognosis. We evaluated the prognostic features of this
      subset of sarcoma. METHODS: Prospective data on 215 patients presenting to
      Memorial Sloan-Kettering Cancer Center with primary extremity superficial soft
      tissue sarcomas between July 1, 1982 and July 1, 1996 were analyzed. Superficial
      sarcomas were defined as subcutaneous tumors not invading the investing fascia of
      the muscle. Analysis was by univariate and multivariate tests for local
      recurrence, metastasis, and tumor mortality. RESULTS: Ninety (42%) patients were
      over 50 years of age, 115 (53%) had high-grade tumors, 53 (25%) had tumors > or =
      5 cm, and 18 (8%) had positive margins following definitive resection. Median
      follow-up was 45 months (range 2 days to 151 months), 31 (14%) patients had local
      recurrences, 20 (9%) had distant metastases, and 15 (7%) died of disease. Five-
      and 10-year actuarial disease-specific survivals were 91% and 85%, respectively.
      On multivariate analysis, age > 50 years predicted local recurrence (RR 5.7; 95%
      CI, 2.4-13.3; p < 0.0001). High grade (RR 4.2; 95% CI, 1.4-12.7; p < 0.006), and
      size > or = 5 cm (RR 4.4; 95% CI, 1.8-11; p < 0.002) predicted distant
      metastases. High grade (RR 7; 95% CI, 1.5-31.4; p < 0.003), size > or = 5 cm (RR
      6.9; 95% CI, 2.3-20.8; p < 0.0006), and positive margins (RR 3.8; 95% CI, 1.2
      12.4; p < 0.006) predicted tumor mortality. CONCLUSION: Primary superficial
      extremity soft tissue sarcomas have a favorable prognosis. Size and grade of
      superficial tumors are the strongest factors in predicting survival.

PMID- 9524708
TI  - Neovascularity and clinical outcome in high-grade extremity soft tissue sarcomas.
AB  - BACKGROUND: Increased tumor neovascularity has been shown to correlate with poor
      prognosis in solid tumors. METHODS: Microvessels were identified by factor VIII
      immunohistochemical staining. Analysis of microvessel counts, tumor
      characteristics, and resection details was performed on 119 primary, high-grade
      extremity soft tissue sarcomas (STS) and correlated with clinical outcome.
      RESULTS: Tumor characteristics and resection details were analyzed and patient
      outcome was examined with respect to local recurrence, distant metastasis, and
      disease-specific survival. Factors found to be significant on univariate analysis
      for all outcome variables were positive microscopic margin and tumor size. A
      positive microscopic margin was found to be a significant risk factor for local
      recurrence (P = .03), distant metastasis (P = .006), and disease-specific
      survival (P = .004). A primary tumor greater than 10 cm in diameter was a poor
      prognostic factor for distant metastasis (P = .03) and disease-specific survival
      (P = .006) when compared to tumors smaller than 10 cm. Microvessel count did not
      correlate with survival nor did it predict distant metastasis or local
      recurrence. Histologic subtypes of STS that have a prominent vascular pattern as
      a diagnostic criterion (i.e., angiosarcoma, liposarcoma, hemangiopericytoma) form
      a subgroup of all STS. Neovascularity in these subtypes showed no relationship to
      clinical outcome. CONCLUSIONS: These data confirm the prognostic importance of
      microscopic margin and tumor size in high-grade extremity STS. Neovascularity
      measured by factor VIII staining had no prognostic significance in these
      mesenchymal tumors, in contradistinction to carcinomas. Alternatively,
      microvessel counts may not accurately represent the angiogenic capacity of STS.
      Therefore, patients with STS who are eligible for anti-angiogenesis clinical
      trials cannot be identified solely by microvessel count.

PMID- 9524709
TI  - Impact on survival by method of recurrence detection in stage I and II cutaneous
      melanoma.
AB  - BACKGROUND: The impact on survival by components of a surveillance program
      (physical examination, blood tests, and chest radiograph) used to detect
      recurrences in patients with cutaneous melanoma was assessed. METHODS: Data were
      collected from medical records and tumor registry information on a historical
      cohort of 1004 patients who presented with AJCC Stage I or II cutaneous melanoma
      at Roswell Park Cancer Institute from 1971 through 1995. RESULTS: Information on
      method of detection was available on 154 out of 174 identified first recurrences
      (89%). Physical examination detected 72% of recurrences, constitutional symptoms
      indicated 17% of recurrences, and chest radiograph revealed 11% of recurrences.
      Blood tests did not predict any recurrence. Only 9 of 17 patients with
      recurrences detected by chest radiograph alone underwent curative surgical
      resection. These patients had a statistically significant prolonged survival
      after diagnosis of recurrence compared to those surgical candidates who did not
      undergo resection. There was no statistically significant difference in overall
      survival between patients with asymptomatic pulmonary recurrences and those whose
      pulmonary recurrences were detected after symptoms of metastatic disease had
      developed. CONCLUSIONS: Most recurrences are detected on physical examination.
      Blood tests have no role in surveillance programs. Chest radiographs can detect
      pulmonary recurrences in a small number of asymptomatic patients at a stage when
      surgery may prolong survival.

PMID- 9524710
TI  - Use of recombinant poxviruses to stimulate anti-melanoma T cell reactivity.
AB  - BACKGROUND: Dendritic cells (DC) are potent professional antigen-presenting cells
      that can activate naive T lymphocytes and initiate cellular immune responses. As
      adjuvants, DC may be useful for enhancing immunogenicity and mediating tumor
      regression. Endogenous expression of antigen by DC could offer the potential
      advantage of allowing prolonged constitutive presentation of endogenously
      processed epitopes and exploitation of multiple restriction elements for the
      presentation of the same antigen. METHODS: DC were prepared from the peripheral
      blood of HLA A*0201 patients with metastatic melanoma in the presence of IL-4
      (1000 IU/mL) and GMCSF (1000 IU/mL). Recombinant vaccinia and fowlpox viruses
      encoding the hMART-1 gene were constructed and used to infect DC. The efficiency
      of infection and expression of the MART-1 antigen were assessed by
      immunohistochemistry and intracellular FACS analyses. Cytotoxic lymphocytes (CTL)
      were generated by the stimulation of CD8+ T cells, with DC expressing the
      recombinant gene. Reactivity of the CTL was determined at weeks 1 and 2 by the
      amount of IFN-gamma released. RESULTS: DC were infected with recombinant
      poxviruses and demonstrated specific melanoma antigen expression by
      immunohistochemistry, immunofluorescence, and intracellular FACS analysis. The
      expression by DC of MART-1 MAA after viral infection was sufficient to generate
      CD8+ T lymphocytes that recognized naturally processed epitopes on tumor cells in
      10 of 11 patients. CONCLUSIONS: Human DC are receptive to infection by
      recombinant poxviruses encoding MAA genes and are capable of efficiently
      processing and presenting these MAA to cytotoxic T cells. The potential advantage
      of this approach is the ability to present specific antigen independent of the
      identification of the epitope or the MHC restriction element. This strategy may
      be useful for the identification of relevant epitopes for a diverse number of HLA
      alleles and for active immunization in patients.

PMID- 9524711
TI  - Lack of effect of particle size on the identification of the sentinel node in
      cutaneous malignancies.
AB  - BACKGROUND: Radiotracers have become a routine technical component of the new
      procedure of intraoperative lymphatic mapping and selective lymphadenectomy.
      Because different colloids have differing physicochemical properties, their
      distribution and uptake may be different. For this reason, the optimal colloid to
      identify and localize the sentinel node remains controversial. METHODS: Nineteen
      consecutive patients with cutaneous malignancies underwent diagnostic
      lymphoscintigraphy with 99mTc-labeled human serum albumin (99mTc-HSA) and
      preoperative lymphoscintigraphy with 99mTc-labeled sulfur colloid (99mTc-SC). The
      results of intraoperative lymphatic mapping and selective lymphadenectomy were
      reviewed. RESULTS: Intraoperative lymphatic mapping and selective node dissection
      were successful in 21 of 22 lymphatic basins (18 of 19 patients). There was
      excellent correlation between the "hot" marker placed on the skin surface when
      99mTc-HSA was used compared with the use of 99mTc-SC. In 20 of 21 lymphatic
      basins the sentinel node both was "hot" and was stained with isosulfan blue.
      CONCLUSIONS: No discernible difference between the ability to localize in the
      sentinel node with these two radiocolloids was identified. For logistical
      reasons, 99mTC-SC appears to be the colloid of choice in intraoperative lymphatic
      mapping.

PMID- 9524712
TI  - Medullary carcinoma of the thyroid: prognostic factors and treatment
      recommendations.
AB  - BACKGROUND: Because medullary thyroid carcinoma accounts for only 7% of all
      thyroid malignancies, data to support treatment strategies are scarce. METHODS:
      We retrospectively reviewed treatment and outcome in 34 patients with MTC treated
      at Roswell Park between 1961 and 1995. Univariate analysis was performed using
      the variables age, sex, tumor size, N stage, and M stage. RESULTS: Median
      survival was 4.7 years, with 51% and 32% of patients alive at 5 and 15 years,
      respectively. Nodal metastases were seen in 76% and distant metastases in 67% of
      all patients. More than 60% of the patients with nodal metastases survived longer
      than 10 years. Once diagnosed with distant metastases, 90% of the patients died
      within 5 years. Local failure rate with lobectomy was 44%, compared to 10% after
      total thyroidectomy (P < .02). Age, extrathyroid extension, and M stage portend a
      poor outcome. Nodal status had no statistically significant impact on survival.
      CONCLUSION: Survival with tumors confined to the thyroid gland is independent of
      nodal status. Long-term survival in patients with distant metastases is rare.
      This study underscores the role of total thyroidectomy in the initial treatment
      and the need to develop effective adjuvant therapy for MTC.

PMID- 9524713
TI  - Characterization of local inflammatory response in an isolated lung perfusion
      model.
AB  - BACKGROUND: Current phase I trials of isolated lung perfusion for treatment of
      pulmonary metastases have an arbitrarily determined length of perfusion. Our
      objective was to examine the temporal course of the local and distant
      inflammatory response as a function of the length of perfusion (ischemia) and
      subsequent reperfusion in an equivalent animal model. METHODS: Sixty male Fischer
      344 rats were randomized into four groups (n = 15). Each group underwent left
      isolated lung perfusion with buffered Hespan for 10, 30, 60, or 90 minutes.
      Subsequently, two subgroups of five animals within each group were allowed to
      reperfuse for 1 or 3 hours, respectively. Non-perfused right lung was used as
      control. At each time point, lung specimens were assayed for TNF-alpha by ELISA
      and histologic sections were examined. RESULTS: There was no significant
      difference between the left and right lung tissue levels of TNF-alpha at the
      termination of the ischemic period. However, on reperfusion, the left lung TNF
      alpha levels increased significantly above the ischemia baseline in all groups,
      with a greater magnitude of rise in the groups with 60 and 90 minutes of
      preceding ischemia (12,757 +/- 1985 vs. 3524 +/- 494 pg/g, and 16,914 +/- 1657
      vs. 6530 +/- 1104 pg/g, respectively; p < 0.05). There was no significant
      elevation in tissue levels of TNF-alpha in the right lung. Histologic changes
      consistent with early pulmonary edema were first detected at 12 hours following
      onset of reperfusion. CONCLUSIONS: Reperfusion following prolonged pulmonary
      ischemia during isolated lung perfusion results in a significant elevation of
      local tissue levels of TNF-alpha and may render the perfused lung vulnerable to
      the adverse effects of the inflammatory cascade.

PMID- 9524715
TI  - Wanted, a toll-free number for advice on suspect cases of foreign animal disease.

PMID- 9524714
TI  - An HLA-restricted, p53 specific immune response from HLA transgenic p53 knockout
      mice.
AB  - BACKGROUND: p53 is over-expressed in most human malignancies and is therefore an
      attractive target for immunotherapy. Unfortunately, a human cytotoxic T cell
      response to p53 is difficult to generate. p53 knockout transgenic mice may
      provide a model to circumvent immunologic tolerance to p53 and develop high
      affinity p53-specific cytotoxic T lymphocytes (CTL). METHODS: p53 knockout, HLA
      A2.1 transgenic mice were generated and immunized with the immunodominant wild
      type p53 nonamer peptide epitope p53149-157. Two weeks later splenocytes were
      harvested and stimulated in vitro with acid-treated, p53 peptide-pulsed syngeneic
      blast cells. Cultures were restimulated weekly with acid-treated, p53 peptide
      pulsed Jurkat cells transfected with the HLA A2.1 gene. Peptide-specific
      cytotoxic activity was measured by chromium release assay, and the resulting CD8+
      effectors were cloned via limiting dilution. RESULTS: P53 peptide-specific CTL
      were generated against p53149-157. Clones generated from the p53149-157 cell line
      demonstrated high affinity and specificity for p53149-157 when presented by HLA
      A2.1+ antigen-presenting cells. The p53149-157 CTL killed only cells
      overexpressing p53 cells that were HLA A2.1+ and did not kill cells with normal
      levels of p53 expression or those that were HLA A2.1-. CONCLUSION: HLA transgenic
      mice not previously exposed to the p53 protein provide a useful model for
      generating high-affinity p53-specific CTL.

PMID- 9524716
TI  - The D'AL School of Equine Massage.

PMID- 9524717
TI  - Crisis at the Bureau of Veterinary Drugs.

PMID- 9524718
TI  - Re-engineering the Bureau of Veterinary Drugs.

PMID- 9524720
TI  - Potential factors affecting the outcome of dogs with a resection of the lateral
      wall of the vertical ear canal.
AB  - The records of 60 dogs that had a resection of the lateral wall of the vertical
      ear canal (Zepp) were examined. The surgical outcomes were evaluated in
      association with the following variables: breed, sex, age of onset of the otitis
      externa, duration of the disease before the surgery was performed, treatment
      received for the otitis externa, the status of the ear and tympanic membrane at
      the time of the surgery, the culture results, and concurrent medical problems.
      The outcome of surgery was acceptable in 45% and unacceptable in 55% of the
      cases. Breed was the only factor that could be correlated with the outcome. The
      procedure failed in 86.5% of the cocker spaniels. When surgical outcomes in
      breeds other than cocker spaniels were evaluated, 63% were acceptable and 37%
      were unacceptable. Sharpeis were found to have an ear canal of small diameter
      compared with that of other breeds and a tendency to have better outcomes.

PMID- 9524719
TI  - The infancy of the CVMA: 1948-1967.

PMID- 9524721
TI  - A comparison of the clinical field efficacy and safety of florfenicol and
      tilmicosin for the treatment of undifferentiated bovine respiratory disease of
      cattle in western Canada.
AB  - We compared the field efficacy of a new antibiotic, florfenicol, with tilmicosin
      in the treatment of naturally occurring undifferentiated bovine respiratory
      disease. Beef calves with rectal temperatures greater than 40.5 degrees C and
      signs compatible with undifferentiated bovine respiratory disease were entered
      into the trial. Calves were randomly assigned to receive either florfenicol (20
      mg/kg bodyweight intramuscularly; 2 injections 48 h apart) or tilmicosin (10
      mg/kg bodyweight subcutaneously; 1 injection). Clinical measures of efficacy
      included mortality, rectal temperature, illness index score, assessment of
      treatment success or failure, and the number of relapses or reinfections.
      Performance was assessed based on weight gains from day 0 to day 90. Two hundred
      and twenty calves entered the trial; 112 received florfenicol and 108 received
      tilmicosin. Seventeen deaths occurred between day 0 and day 90, but only 10
      during the 28-day trial period. Seven calves receiving tilmicosin died, compared
      with 3 receiving florfenicol (P = 0.20). Of the 220 initial treatments, 45 (20%)
      were categorized as treatment failures; 27 in the tilmicosin group and 18 in the
      florfenicol group (P = 0.10). The number of calves experiencing a 2nd relapse was
      significantly different, with 17 of 30 (57%) calves on tilmicosin compared with 7
      of 26 (27%) calves on florfenicol relapsing at least twice (P = 0.02). Average
      daily gains over 90 days were 1.55 kg/day for florfenicol-treated calves and 1.51
      kg/day for tilmicosin-treated calves. No significant adverse reactions were
      noticed with either drug. Results indicate that florfenicol and tilmicosin are
      comparable in the treatment of undifferentiated bovine respiratory disease in
      western Canada.

PMID- 9524722
TI  - Gastric ulceration and suspected vitamin A toxicosis in grower pigs fed fish
      silage.
AB  - In 3 feeding trials, gastric ulceration was diagnosed in 2 of 12 lame and
      recumbent grower pigs fed a diet of 50% fish silage produced from the offal of
      farmed Atlantic salmon. Premature femoral physeal closure and elevated serum
      retinyl palmitate levels, features of vitamin A toxicosis, were also observed.

PMID- 9524723
TI  - Immune-mediated hemolytic anemia associated with trimethoprim-sulphamethoxazole
      administration in a horse.
AB  - A 10-year-old, thoroughbred gelding was administered sulphonamide drugs during
      surgical treatment of guttural pouch mycosis. The horse became anemic and a
      diagnosis of immune-mediated hemolytic anemia was made after other causes of
      anemia had been ruled out. The anemia resolved after the drugs were withdrawn.

PMID- 9524724
TI  - Ferret adrenal-associated endocrinopathy.

PMID- 9524725
TI  - Clinical pathology interpretation.

PMID- 9524726
TI  - Extrinsic modulation of spike afterpotentials in rat hypothalamoneurohypophysial
      neurons.
AB  - 1. Magnocellular neurosecretory cells (MNCs) in the rat hypothalamus adopt a
      phasic pattern of spike discharge under conditions demanding enhanced vasopressin
      release, such as during dehydration or hemorrhage. The emergence of phasic firing
      minimizes the occurrence of secretory fatigue from the axon terminals of MNCs,
      thereby maximizing vasopressin release from the neurohypophysis. 2. Intracellular
      and whole-cell recordings from hypothalamic slices or explants in vitro have
      shown that phasic firing is supported by the presence of a plateau potential
      which arises from the summation of spike depolarizing afterpotentials (DAPs).
      Modulatory actions of neurotransmitters on the amplitude of the DAP, therefore,
      represent possible mechanisms by which the expression of phasic firing may be
      regulated in vivo. 3. Here we review the basis for phasic firing in MNCs of the
      rat supraoptic nucleus and present recent findings concerning the direct and
      indirect mechanisms through which selected neurotransmitters have been found to
      regulate the amplitude of DAPs.

PMID- 9524727
TI  - Intrinsic controls of intracellular calcium and intercellular communication in
      the regulation of neuroendocrine cell activity.
AB  - 1. The magnocellular hypothalamoneurohypophysial system, consisting chiefly of
      the supraoptic and paraventricular nuclei and their axonal projections to the
      pituitary neural lobe, has become a model for the study of neuroendocrine cell
      morphology, function, and plasticity. 2. Decades of research have produced a
      wealth of knowledge about the physiological conditions that activate this system,
      the peripheral target tissues affected by its outputs, and its capacity to
      undergo use-dependent, reversible reorganization. 3. Earlier research on the
      neural control of this system concentrated largely on the synaptic inputs that
      influence the activity of these magnocellular neurons and, while that task is
      still far from completed, methods have now been developed that permit insights to
      be gained into the control exercised by intrinsic cellular and molecular
      mechanisms. 4. This article reviews the current state of knowledge of roles
      played by these intrinsic mechanisms, including influences of intracellular
      calcium buffering, calcium release from internal stores and intercellular
      communication through gap junctions, in the control of neuroendocrine cell
      activity.

PMID- 9524728
TI  - Synaptic modulation of oscillatory activity of hypothalamic neuronal networks in
      vitro.
AB  - 1. Rhythmic bursts of action potentials in neurosecretory cells are a key factor
      in hypothalamic neurosecretion. Rhythmicity and synchronization may be
      accomplished by pacemaker cells synaptically driving follower cells or by a
      network oscillator. 2. In this review we describe a hypothalamic cell culture
      which may serve as a model for a hypothalamic network oscillator. An overview is
      given of neurochemical phenotypes, synaptic mechanisms and their development,
      properties of receptors for fast synaptic transmission, and membrane properties
      of cells in dissociated rat embryonic hypothalamic culture. 3. Rhythmic activity
      spreads in the cultured network through synapses that release glutamate,
      activating a heteromultimeric AMPA-type receptor containing a GluR2 subunit which
      is associated with a high-conductance channel for Na+ and K+. Rhythmic activity
      is controlled by synapses that release GABA to activate GABAA receptors. The
      presumed function of the two receptor types is facilitated by their respective
      location, GABAA receptors predominating near the soma and AMPA receptors being
      abundant in dendrites. 4. Network oscillators may be more reliable for the
      presumed function than single-cell oscillators. They are controlled through
      synaptic modulation, which may prove to represent a process important for the
      release of hormones.

PMID- 9524729
TI  - Membrane excitability and secretion from peptidergic nerve terminals.
AB  - 1. Thin slices of the posterior pituitary can be used as a preparation for the
      study of biophysical mechanisms underlying neuropeptide secretion. Patch-clamp
      techniques in this preparation have revealed the properties of ion channels that
      control the excitability of the nerve terminal membrane and have clarified the
      relation between Ca2+ and exocytosis. 2. Repetitive electrical activity at high
      frequencies broadens action potentials to allow more Ca2+ entry and thus enhance
      exocytosis. Action potential broadening results from the inactivation of a
      voltage-dependent K+ channel. 3. When repetitive electrical activity is
      sustained, secretion is depressed. This depression can be attributed in part to
      action potential failure caused by the opening of a Ca(2+)-activated K+ channel.
      This channel can be modulated by protein kinases, phosphatases, and G-proteins.
      4. The inhibitory neurotransmitter GABA activates a GABAA receptor in the nerve
      terminal membrane. The gating of the associated Cl- channel depolarizes the
      membrane slightly to inactivate voltage-gated Na+ channels and block action
      potential propagation. 5. The response of the nerve terminal GABAA receptor is
      enhanced by neuroactive steroids and this can potentiate the inhibition of
      neurosecretion by GABA. The action of neurosteroids at this site could play a
      role in changes in neuropeptide secretion associated with reproductive
      transitions. 6. Ca2+ channels in the nerve terminal membrane are inactivated by
      sustained depolarization and by trains of brief pulses. Ca2+ entry promotes Ca2+
      channel inactivation during trains by inhibiting the recovery of Ca2+ channels
      from inactivation. The inactivation of Ca2+ channels can play a role in defining
      the optimal frequency and train duration for evoking neuropeptide secretion. 7.
      Measurements of membrane capacitance in peptidergic nerve terminals have revealed
      rapid exocytosis and endocytosis evoked by Ca2+ entry through voltage-gated Ca2+
      channels. Exocytosis is too rapid to account for the delays in neuropeptide
      secretion evoked by trains of action potentials. Endocytosis sets in rapidly
      after exocytosis with a time course comparable to that of the rapid endocytosis
      observed in nerve terminals at rapid synapses. Our results support the finding in
      rapid synaptic nerve terminals that endocytosis is inhibited by intracellular
      Ca2+. Multiple pools of vesicles were revealed, and these pools may reflect
      different stages in the mobilization and release of neuropeptide.

PMID- 9524730
TI  - Excitation-secretion coupling in mammalian neurohypophysial nerve terminals.
AB  - 1. Oxytocin and vasopressin secretion from the neurohypophysis (NHP) is evoked by
      strongly patterned bursts of action potentials. We studied excitation-secretion
      coupling in single isolated terminals of rat NHP using patch clamp and
      capacitance detection techniques. 2. The secretory response evoked by trains of
      depolarizing pulses consisted of two discrete phases. Ca2+ entry during pulses
      early in the train did not elicit secretion. Exocytotic responses began only
      after a characteristic amount of total Ca2+ entry called "threshold". 3. In the
      postthreshold secretory phase, exocytotic events occurred during or immediately
      after depolarizing pulses, indicating that the final Ca(2+)-dependent step is
      triggered by high Ca2+ concentrations near the plasma membrane that dissipate
      rapidly after channel closure. Secretion was sensitive to both the concentration
      and species of Ca2+ chelator. BAPTA, a Ca2+ chelator with rapid Ca2+ binding
      kinetics, was more effective than EGTA in diminishing secretion. 4. The
      "threshold" amount of Ca2+ was determined by the concentration, but not species,
      of Ca2+ chelator. The threshold value was constant even when Ca2+ entry
      parameters were varied over a broad range of current amplitudes, pulse durations,
      and number of pulses, indicating that it did not require high Ca2+ concentrations
      near the plasma membrane. 5. These results suggest that the secretory response to
      a train of pulses consists of a Ca(2+)-dependent preparatory step that must be
      completed before subsequent Ca2+ entry can elicit exocytosis. 6. Exocytotic
      responses during single trains showed strong depression at a step subsequent to
      Ca2+ entry. Recovery from depression required 30-60 sec. 7. The properties of
      threshold secretion observed in NHP terminals are discussed in terms of current
      models of secretion.

PMID- 9524731
TI  - Regulation of crustacean neurosecretory cell activity.
AB  - 1. The X organ-sinus gland system is a conglomerate of 150-200 neurosecretory
      cells in the eyestalk of crustaceans. It is the source of a host of peptide
      neurohormones which partake in the control of a wide range of physiological
      functions. Distinct families of X organ peptides have been chemically
      characterized: (a) two chromatophorotropic hormones of small sizes, one of 8
      residues and the other of 15-20 residues; and (b) three metabotropic hormones of
      high molecular weight (70-80 residues), related to the control of blood sugar
      levels, molting, and gonad activity. Some of these hormones have been identified
      only in crustaceans; others are common to various arthropod groups. A number of
      peptides orginally described in other zoological groups are also present in the X
      organ-sinus gland system; such is the case for members of the FMRF-amide family,
      enkephalins, and other peptides. 2. Cells specifically containing each hormone
      have been located in the X organ and some information is available on the
      cellular and molecular substrate of the biosynthesis, transport, storage, and
      release of various hormones. The electrical activity of X organ neurons has been
      recorded at the cell soma, arborizations, axons, and neurosecretory terminals.
      Conspicuous regional differences have been defined for the various patterns of
      activity, as well as the distribution of their underlying ion currents. 3. The
      release of hormones and the electrical activity of X organ neurons are regulated
      by environmental and endogenous influences, such as light and darkness, stress,
      and circadian rhythms. These influences appear to be mediated by a host of
      neurotransmitters/modulators, most noticeably, gamma-aminobutyric acid, 5
      hydroxytryptamine and other amines, and enkephalins. Each of these mediators acts
      upon a definite ionic substrate(s) and exerts specific regulatory effects on X
      organ cell activity. A given neuron may be under the control of more than one
      neurotransmitter, and a transmitter may mediate different and even opposite
      influences on different neurons.

PMID- 9524734
TI  - Fasting plasma insulin levels in an unselected Prague suburban population.
AB  - OBJECTIVE: The aim of the study was to determine the levels of fasting plasma
      insulin in an unselected population of a Prague suburban community and correlate
      the levels of insulin with other metabolic and anthropometric parameters which
      could be directly or indirectly associated with insulin levels. RESEARCH DESIGN
      AND METHODS: A total of 835 adult inhabitants, the Prague suburban community,
      were examined. Mean age of examined people was 44.9 +/- 16.9 years, the group
      included 370 men and 465 women, 189 of the latter were in the menopause. The
      parameters examined included the fasting plasma levels of insulin, glycaemia,
      total cholesterol, HDL cholesterol and triacylglycerols; LDL cholesterol and,
      using the basic anthropometric data, the body mass index (BMI) and the waist/hip
      ratio (WHR) were calculated. RESULTS: The levels of all parameters were divided
      in ten-year groups of men and women. The average levels of fasting plasma insulin
      in all ten-year groups of men and women were normal. We found in the men small
      but constant rise of fasting insulinaemia in the decades. This was not observed
      in women, where the insulin levels were similar up to the time after menopause,
      then the level of average plasma insulin rose significantly. We found the
      positive correlation of plasma insulin levels with triacylglycerol levels (p < or
      = 0.001), BMI (p < or = 0.001) and WHR (p < or = 0.001) and a negative
      correlation with plasma HDL cholesterol (p < or = 0.001) in the whole group of
      probands. No significant correlation was demonstrated between fasting
      insulinaemia and total or LDL cholesterol. When dividing the group by age and
      sex, the strongest positive correlations were seen between insulin and
      triacylglycerols, glycaemia, BMI, and WHR, and negative correlations between
      insulin and HDL cholesterol. CONCLUSION: Fasting plasma insulin levels in an
      unselected population were within the normal range, but follow a continuous and
      steady upward course in men while did not change until after the menopause when
      they bounce in women; compared to insulin levels in younger women, insulinaemia
      does not increase up to 55 years of age. The strongest positive correlations were
      demonstrated between plasma insulin and triacylglycerols, and between insulin and
      BMI and WHR in men and postmenopausal but not premenopausal women whereas a
      negative correlation was observed between fasting plasma insulin and HDL
      cholesterol.

PMID- 9524735
TI  - Occurrence of Salmonella enteritidis phage type 21 in Tyrol.

PMID- 9524732
TI  - Hypothalamic and hypophyseal regulation of growth hormone secretion.
AB  - 1. Regulation of pulsatile secretion of growth hormone (GH) relies on
      hypothalamic neuronal loops, major transmitters involved in their operation are
      growth hormone releasing hormone (GHRH) synthetized mostly in arcuate nucleus
      (ARC) neurons, and somatostatin (SRIH), synthetized both in hypothalamus
      periventricular (PVe) and ARC neurons. 2. Neurons synthetizing both peptides can
      inhibit each other in a reciprocal manner. Other neuropeptides synthetized in ARC
      neurons, such as galanin, or in ARC interneurons, such as neuropeptide Y (NPY),
      are able to modulate synthesis and release of GHRH and SRIH into the
      hypothalamohypophyseal portal system. 3. In addition, the hitherto
      uncharacterized endogenous ligand of the recently cloned growth hormone releasing
      peptide receptor, expressed mostly in the ARC, triggers GH release, presumably by
      actions on ARC interneurons. 4. Thyroid, gonadal, and adrenal steroid hormones
      also affect the GHRH-SRIH balance; a differential distribution of sex steroid
      receptors in the ARC and the PVe is likely to account for the different pattern
      of GH secretion in male and female animals. 5. Growth hormone itself is able to
      inhibit the amplitude of GH secretory episodes and to increase their frequency,
      by entering the brain (presumably by receptor-mediated internalization at the
      level of the choroid plexus) and acting subsequently on ARC neurons. 6. At the
      pituitary level, major neurotransmitters regulating GH cells act on receptors of
      the VIP/PACAP/GHRH family and of the somatostatin family, in particular, sst2 and
      sst3. Those are coupled to accumulation of cAMP as a second messenger. 7. In
      addition, patch-clamp experiments and measurement of intracellular Ca2+ indicate
      that GH cells present characteristic, GHRH-dependent, but self-maintained Ca2+
      spikes and [Ca2+]i transients, which reflect adaptive mechanisms to constraints
      of episodic release. 8. Recent data on transcription factors affecting GH gene
      expression and somatotrope differentiation are also summarized. 9. Regulation and
      differentiation of somatotropes also depend upon paracrine processes within the
      pituitary itself and involve growth factors and several neuropeptides, for
      instance, vasoactive intestinal peptide, angiotensin 2, endothelin, and activin.
      10. Finally, characteristic changes occur in the GH secretory pattern under
      discrete, pathological conditions, such as abnormal growth and dwarfism,
      diabetes, and acromegaly, as well as during inflammatory processes.

PMID- 9524733
TI  - Modulating mechanisms of neuroendocrine cell activity: the LHRH pulse generator.
AB  - 1. Luteinizing hormone-releasing hormone (LHRH), synthesized in specialized
      neurons in the hypothalamus, is the prime regulator of reproduction. In its
      absence, reproductive development is arrested and disorders of LHRH secretion
      result in several reproductive dysfunctions. 2. The LHRH neuronal network plays a
      paramount role in the regulatory loop controlling gonadal homeostasis. LHRH input
      to the pituitary gland maintains gonadotropin secretion, which, in turn, is
      responsible for gonadal trophism. Steroidal and peptidergic hormones from the
      gonad close the regulatory system by establishing negative (male and females) and
      positive (females) feedback loops. 3. Interestingly, LHRH input to the pituitary
      is intermittent rather than continuous. In fact, continuous exposure to LHRH
      results in paradoxical hypogonadism. Several studies in animals have provided
      direct evidence for episodic secretion of LHRH into the hypophyseal portal
      system. However, the nature of the system(s) responsible for the generation of
      the LHRH pulsatile profile is not currently known. The recent observation that
      immortalized LHRH neurons secrete LHRH in a pulsatile manner suggests that the
      pulse generating mechanism resides within the LHRH neuronal network. 4. In this
      overview, we compile several lines of evidence supporting this notion and put
      this characteristic of LHRH neurons in perspective with gonadal influences both
      internal and external to the LHRH neuronal network. Some recent data regarding
      the site of action of gonadal steroids on the LHRH neuronal system, the
      functional significance of galanin colocalization with LHRH, and the role of
      nitric oxide in the pulse generating mechanism are also discussed.

PMID- 9524736
TI  - Environmental epidemiology of malignancies. The central European perspective.
AB  - The epidemiology of tumour diseases is one of the basic fields of non-infectious
      epidemiology. When in the first half of this century the most serious infections
      had been put under control in Europe and North America other kinds of diseases
      such as carcinomas emerged. Incidence of these diseases seem to be epidemical,
      exactly in those parts of the world. Carcinomas have been recorded as the second
      largest group of death causes nowadays. Despite frequent efforts to refer to the
      tumour diseases as the civilisation evils, we have to weigh critically the
      opinion that malignant tumours are the privilege of industrial countries whereas
      the primitive nations have recorded these types of diseases rarely. The Cancer
      Register in Mengo Hospital, Kampala, of 1897-1956 and other evidence have failed
      to confirm the lower cancer incidence in the local population at the beginning of
      the colonisation period than it was in Europe of that time. The paleopathological
      analysis of skeletal relicts in Central Europe burial places during the ceramic
      volute era near Stuttgart, Germany, have proved the total proportion of over 10%
      of traces indicating the presence of tumours in the available complete skeletons.
      The authors discuss the epidemiology of cancer, risk factors and chances of
      prevention.

PMID- 9524737
TI  - Trends in the incidence of problematic drug addicts in the Czech Republic, 1995
      1996.
AB  - During 1996 there were 3,252 newly registered problematic drug users (incidence
      31.5/100,000 inhabitants) while in 1995 it was only 2,470 drug users
      (23.9/100,000 inhabitants). Trends in the incidence of problematic drug users and
      their age structure and regional distribution between 1995-1996 characterise the
      current drug scene in the Czech Republic as follows: Slightly upward trend of the
      incidence of problematic drug users with prevalent position of pervitin. Dramatic
      increase in heroin use in 1995 has changed in slower growth of the number of new
      users in 1996. Proportion of men to women is totally 2:1 with major differences
      between individual drug types. Gradual decrease in the average age of problematic
      users, especially women, and decrease in the age of first use of primary drug.
      The most affected age group are young people between 15 and 19. Increasing number
      of problematic users under 15 is also alarming. Major differences in the
      incidence of problematic users and in the different representation of individual
      types of drugs in regions with prevalence of Northern Bohemia and Prague. High
      and gradually upward trend of injection drug users; national average nears to 60%
      and thus exceeds Prague and Northern Bohemia regions. Injection users under 19
      represent 1/3 of all registered problematic users and approximately 50-60% of all
      injection users.

PMID- 9524738
TI  - Air-borne microorganisms in the metropolitan area of Graz, Austria.
AB  - Urban and rural regions are affected by different microorganism loads depending
      on their structure and utilization. At 7 sampling sites in the metropolitan area
      of Graz, counts of airborne bacteria as well as yeasts and molds were conducted
      over a one-year period at two-week intervals. Bacteria and yeasts/molds counts in
      a village area to the South of Graz dominated by agriculture exceeded the
      corresponding counts in a suburban residential area fourfold (327 CFU/m3 air
      bacteria) and twofold (185 CFU/m3 air-yeasts/molds) respectively. In the vicinity
      of a composting facility located in the same residential area, microorganism
      counts exceeded those of the neighboring "unaffected" area by 29% in the case of
      bacteria and by 54% in the case of yeasts/molds. At an industrial and business
      site with heavy traffic, the counts are twice that of the area affected by the
      composting facility (146 CFU/m3 for bacteria and 168 CFU/m3 for yeasts/molds).
      The proportion of Aspergillus fumigatus is highest in the village area with 23%,
      compared to 10% in the open land. 49% of the bacteria and 54% of the yeasts and
      molds can be shown on stages 4-6 of the Andersen-Volumetric-Sampler registering
      the respirable particle sizes.

PMID- 9524739
TI  - Health status of workers of a thermal power station exposed for prolonged periods
      to arsenic and other elements from fuel.
AB  - The Novaky Power Station (NPS) has been using since 1953 as fuel coal with a high
      content of As and with a low content of other metals. This involves a constant
      risk for the workers as well as pollution of the surroundings. The authors
      described 16 cases of chronic As intoxication in NPS workers after 22.3 +/- 8.4
      years of exposure (especially stokers, maintenance workers, boiler cleaners).
      Among clinical symptoms prevailed sensory and motor polyneuropathy (13 cases),
      pseudoneurasthenic syndrome (10 cases), toxic encephalopathy (6 cases) and nasal
      septum perforation (2 cases). After 1989 the intoxications with As did not occur
      any more due to technical measures and health protection of the workers. The
      authors present a review of actual results of clinical, haematological and
      biochemical investigations and tests for metals (AAS methods) in biological
      materials of workers at risk in NPS (n = 70), exposed on average for 11.9 +/- 0.5
      years, of average age 35.91 +/- 1.7 years (mean +/- SE) and compared the results
      to a matched control group of blood donors not exposed to metals (n = 29). In NPS
      workers significantly lower Hb values, higher serum creatinine, higher serum beta
      2-microglobulin, higher As content in hair as well as higher serum Mn and Pb
      concentrations compared with the C-group were found. The exposed group had
      significantly lower serum Se concentrations (0.64 +/- 0.025 mumol/l (mean +/- SE)
      compared to Se levels of persons from an adjacent district. The authors stress
      the necessity of individual evaluation of the metal concentrations in relation to
      clinical findings. With prolonged exposure the situation can become more urgent
      not only because of chronic poisoning but also because of the cancerogenic
      effects of these elements on the human organism.

PMID- 9524740
TI  - Trends in cigarette sales and lung cancer mortality in four central European
      countries.
AB  - Remarkable increases in lung cancer risk have recently been observed in the
      Central European (CE) area. This study examines the patterns of lung cancer
      mortality rates and cigarette sales in 1965-1989 in four CE countries with a
      total population of 64.2 million and 31,000 deaths from lung cancer in the last
      year under study. The patterns of increases in cigarette sales during the 1960s
      and 1970s were different by country, and, in the 1980s, the consumption in
      Hungary and Poland exceeded 3,000 pieces of cigarettes/year per adult (age 15
      years and older). Among men, the lung cancer death rates in 1989 for the Czech
      Republic (75.8/100,000, age-adjusted to the world standard), Hungary (74.0),
      Poland (69.4) and Slovakia 68.7) ranked among the highest in Europe, the trends
      by country largely reflecting the varied prevalence and duration of smoking in
      previous decades. The age-adjusted lung cancer death rates for females of the
      same countries (9.3, 14.4, 9.4, and 6.8/100,000, respectively) were still much
      lower than in the most afflicted Western countries (Scotland, USA, Canada,
      England, Denmark), however, rapidly increasing. In more recent birth cohorts,
      there was some decline in lung cancer mortality rates among men, but not among
      women; these trends in young adult life are known to spread to older age groups
      in future years, and, therefore, have been suggested to predict future changes in
      older age groups. Hence, an increasing trend in lung cancer mortality can be
      predicted for the female population of the four countries under study which will
      continue probably well beyond the turn of the century. In most of these
      countries, the current increasing trend in men can be expected to reach a plateau
      (and later a decline) sooner than in women. This outlook underlines the urgent
      need for comprehensive lung cancer prevention with control of smoking in women as
      a priority.

PMID- 9524741
TI  - Survey of the microbiological quality of bottled water.
AB  - Three different types of bottled water had counts of psychrophilic bacteria
      (aerobic colony count at 22 degrees C) ranging from 10(0)-10(4) colony forming
      unit/1 ml. The most frequent type of bottled water to exceed limits for
      psychrophilic microorganisms was still table water. The growth of psychrophilic
      microorganisms of up to 10(4) CFU/ml began over the six month storage period.

PMID- 9524742
TI  - The role of psychological factors in questionnaire-based studies on routes of
      human toxoplasmosis transmission.
AB  - The paper studies impacts of particular toxoplasmosis risk factors (consumption
      of raw meat and contact with cats), their interactions, and their relationship
      with the personality of the subjects. Among 243 men and 343 women the frequency
      of subjects with antitoxoplasma immunity was 26.6% and 21.6%, respectively. The
      association of antitoxoplasma immunity (assessed by the toxoplasmin skin test)
      with the two risk factors was estimated by log-linear analysis. Reported contact
      with cats has no influence on the probability of having antitoxoplasma immunity
      (P = 0.23) while the consumption of raw meat increased this probability (P =
      0.0008). Very strong positive association between the contact with cats and the
      raw meat consumption was found among subjects without toxoplasmosis (P = 0.0028),
      suggesting that among these persons some subjects either incorrectly assessed
      their exposition to the risk factors or provided false data during the interview.
      The results of logistic regression suggest that the contact with cat and the
      consumption of raw meat are associated with particular personality traits.
      However, these traits differ from those associated with antitoxoplasma immunity
      suggesting that the correlation between antitoxoplasma immunity and consumption
      of raw meat reflects epidemiological importance of the raw meat rather than a
      correlation of both factors (raw meat consumption and probability of acquiring
      toxoplasmosis) with the subjects personality.

PMID- 9524743
TI  - Long-term monitoring of the immune reactivity of stainless steel welders.
AB  - The immune reactivity of stainless steel welders (n = 22-53) was evaluated in a
      three year's study. The results (phagocytic activity, cellular and humoral
      immunity) were statistically compared with those in control group of non-exposed
      persons from the same plant (n = 14-23) and with long-term laboratory reference
      values (LRV) (n = 14-311). In welders several changes were found when compared to
      the LRV: in humoral response there were higher prealbumin, lysozyme, circulating
      immune complexes and lower IgG. In phagocytic tests there were lower ingestion,
      bactericidal activity and higher metabolic activity of peripheral mononuclear
      leucocytes. In cellular immunity the marked lymphocytosis, higher counts of T
      lymphocytes, CD4+ and CD8+ lymphocytes were noticed. After lowering the
      concentrations of metals in the working area there were trends to normal values
      in some parameters [relative numbers of T-lymphocytes, relative number of CD4+
      lymphocytes, phagocytic activity, metabolic activity of leucocytes (INT index),
      IgA, complement C3, transferrin]. The extent and the length of the exposure to
      welding fumes, smoking and changed conditions at working place were followed as
      well.

PMID- 9524744
TI  - Determination of the mycotoxin fumonisins in gluten-free diet (corn-based
      commodities) in the Czech Republic.
AB  - The fumonisins, mycotoxins produced by Fusarium moniliforme, are known to occur
      worldwide as natural contaminants of corn. They are associated with several
      animal diseases and are a potential threat to human health. A total of 127
      samples of corn-based foods (gluten-free diet) in the Czech Republic were
      analysed by Ridascreen Fumonisin Fast ELISA methods in years 1995-1996. Eighty
      eight % of the corn-based foods were found to be positive for fumonisins (FB1,
      FB2, FB3) and 12% of the examined corn-based foods laid below of a determination
      limit which was about 9 ng fumonisins/g corn-based foods. The highest fumonisin
      contamination levels were recorded in extruded corn products containing up to
      1,808 micrograms/kg of fumonisins. Levels ranging from < 9 to 1,243 ng/g
      fumonisins were detected in polenta. Lower levels of fumonisins were found in
      other commodities, such as corn flour (up to 487 ng/g), corn instant porridge (up
      to 788 ng/g), and corn pastes (511 ng/g). Intake of fumonisins from several corn
      based foods (gluten-free diet) for the population with coeliac disease was
      estimated. The highest estimate of exposure dose of fumonisins was determined
      from corn-extruded bread: 3.2 micrograms/person/day (mean of measured values).
      Daily intake of fumonisins from polenta is expected 2.8 micrograms/person/day
      (mean). The lower exposure dose of fumonisins we can expect from corn instant
      porridge, corn postes and other corn products--corn and amaranth biscuit, corn
      beverage: 0.9, 1.1 and 0.3 micrograms/person/day (mean) respectively.

PMID- 9524745
TI  - Growing importance of non-Candida species as opportunistic pathogens.
AB  - A 40-year study of C. albicans, non-C. albicans species and non-Candida species
      in the excretions of patients with different diseases is described. An increase
      of non-C. albicans, and non-Candida species since 1980 has been determined. The
      study is completed by a review of new and emerging yeasts.

PMID- 9524746
TI  - Characterization of Plesiomonas shigelloides from diarrheic children.
AB  - Infrastructure of 29 P. shigelloides strains isolated as the only positive
      finding from children with diarrhea (biochemical properties, antigenic structure,
      antigenic relationship to shigellae, ATB susceptibility and plasmids) were
      described. A big variety of 22 serovars in a relatively small number of strains
      was found, inclusive four new 0 (093, 094, 095 and 096) and one new H (H46)
      antigen. Some strains belonged to the so-called "Schubert antigenic scheme" the
      serovars of which come of surface water of small ponds in Germany.

PMID- 9524747
TI  - Summary report the Joint WHO/IOMEH Workshop on Human Exposure Assessment in
      Environmental Health Decision-Making. Sosnowiec, Poland, 19-23 November 1996.

PMID- 9524748
TI  - The telomere and telomerase: how do they interact?
AB  - The tandemly repeated DNA sequence of telomeres is typically specified by the
      ribonucleoprotein enzyme telomerase. Telomerase copies part of its intrinsic RNA
      moiety to make one strand of the telomeric repeat DNA. Recent work has led to the
      concept of a telomere homeostasis system. We have been studying two key physical
      components of this system: the telomere itself and telomerase. Mutating the
      template sequence of telomerase RNA caused various phenotypes: (1) mutating
      specific residues in the ciliate Tetrahymena and two yeasts showed that they are
      required for critical aspects of telomerase action; (2) certain mutated telomeric
      sequences caused a previously unreported phenotype, i.e. a strong anaphase block
      in Tetrahymena micronuclei; and (3) certain template mutations in the telomerase
      RNA gene of the yeast Kluyveromyces lactis led to unregulated telomere
      elongation, which in some cases was directly related to loss of binding to K.
      lactis Rap1p. Using K. lactis carrying alterations in the genes for Rap1p and
      other silencing components, we proposed a general model for telomere length
      homeostasis: namely, that the structure and DNA length of the DNA-protein complex
      that comprises the telomere are key determinants of telomerase access, and hence
      the frequency of action of telomerase, at the telomere.

PMID- 9524749
TI  - Telomerase and the chromosome end replication problem.
AB  - Telomerase, the enzyme that extends chromosomal DNA ends in most eukaryotes,
      contains essential RNA and protein subunits. We have been studying telomere
      replication in hypotrichous ciliates such as Euplotes aediculatus, which have
      numerous short macronuclear DNA molecules and therefore are highly enriched in
      telomeres and in telomerase. Cloning and sequencing genes for the RNA subunits
      from several ciliates revealed that telomerase RNAs with insignificant nucleotide
      sequence homology nevertheless form a common secondary structure. Affinity
      chromatography based on the sequence of the RNA subunit was used to purify the
      Euplotes telomerase as an active ribonucleoprotein enzyme. Two protein subunits,
      123 kDa and 43 kDa, were identified. The finding of a yeast homologue to the 123
      kDa subunit suggests that telomerase protein components may be much more highly
      conserved in evolution than the RNA subunits. The purified Euplotes telomerase
      has no activity with blunt-ended DNA primers, but instead requires a four to six
      nucleotide single-stranded 3' tail. This result supports a model for telomere
      replication in which other activities such as helicases or nucleases activate
      replicated DNA for extension by telomerase, a model that may be applicable to
      telomere replication in diverse eukaryotes.

PMID- 9524750
TI  - The role of the EST genes in yeast telomere replication.
AB  - We have recently completed a large mutant screen designed to identify new mutants
      of Saccharomyces cerevisiae with a telomerase-like defect. From this screen; 22
      mutants were identified that mapped to three genes, called EST1, EST2 and EST3,
      as well as a novel EST-like mutation in a fourth gene, previously identified as
      CDC13. Mutations in each of these genes give rise to phenotypes that are
      indistinguishable from those observed when TLC1, encoding the yeast telomerase
      RNA, is deleted. In addition, genetic analysis indicates that all four genes
      function in the same pathway for telomere replication as defined by TLC1, the one
      known component of telomerase. This indicates that these genes encode factors
      that are essential in vivo for telomerase function. Genetic and biochemical
      analyses have shown that EST1 and CDC13 encode single-stranded telomeric DNA
      binding proteins, suggesting that these two proteins may function to mediate
      access of telomerase to the end of the telomere.

PMID- 9524751
TI  - Drosophila telomere elongation.
AB  - Drosophila melanogaster has an unusual telomere elongation mechanism. Instead of
      short repeats that are synthesized by telomerase, long retrotransposons, HeT-A
      and TART, transpose to the ends of chromosomes. This mechanism generates tandem
      arrays of these elements at the chromosome ends, in which all elements are
      oriented with their oligo(A) tails towards the centromere. Structural features of
      HeT-A and TART elements may provide clues as to their transposition mechanism.
      Drosophila telomere length polymorphism is mainly due to terminal retrotransposon
      arrays that differ between chromosome tips and that change with time. In
      addition, stable terminal chromosome deletions can be generated that do not
      contain terminal HeT-A and TART arrays, suggesting that, unlike the equivalent
      terminal repeats in yeast and humans, the presence and length of terminal arrays
      in Drosophila may not be critical for cell cycle progression.

PMID- 9524752
TI  - Rap1p and telomere length regulation in yeast.
AB  - Telomere length in the yeast Saccharomyces cerevisiae is under stringent genetic
      control such that a narrow length distribution of TG1-3 repeats is observed.
      Previous studies have shown that Rap1p, which binds to the double-stranded
      telomeric repeats, plays a role in regulating repeat length: point mutations in
      the Rap1p C-terminus often result in a higher average telomere length and
      deletion of this region causes extreme telomere elongation. We have investigated
      further the role of Rap1p in this process. Our results suggest that telomere
      length is regulated by a negative feedback mechanism that can sense the number of
      Rap1p molecules bound at the chromosome end. This length regulatory mechanism
      requires two other proteins, Rif1p and Rif2p, that interact with each other and
      with the Rap1p C-terminus. Although the same C-terminal domain of Rap1p is also
      involved in the initiation of telomere position effect (telomeric transcriptional
      silencing), this Rap1p function appears to be separate from, and indeed
      antagonistic to, its role in telomere length regulation.

PMID- 9524753
TI  - Chromatin and ageing in yeast and in mammals.
AB  - Genetic studies have identified genes that appear to regulate the pace of ageing
      in model systems and in humans. The molecular analysis of these genes will
      provide insight into causes of ageing. Here I discuss recent findings in yeast
      that suggest possible mechanisms of ageing and relate them to the disease of
      Werner's syndrome, which causes symptoms of premature ageing in humans.

PMID- 9524754
TI  - The limited reproductive life span of normal human cells in culture.
AB  - It has been suggested that the limited reproductive life span of normal (diploid)
      cells in culture may be explained by an inevitable shortening of one or more
      telomeres. The hypothesis is that one of the shortened telomeres will either
      generate a specific signal or will invoke a DNA damage checkpoint, in either case
      causing that cell to leave the cell cycle irreversibly. To assess this
      hypothesis, I review what constitutes the limited life span of cells in culture.
      Careful inspection of the kinetics of the life span of diploid cells in culture
      has shown that the limited life span arises because a fraction of newborn cells
      irreversibly leave the cell cycle at each division; and this fraction of
      reproductively sterile cells increases steadily throughout the life span of the
      culture. Cell fusion experiments suggest that only a small number of genes are
      involved in preventing continued cell growth, but that at least two independent
      mutation events are required to immortalize human cells, although only one event
      is sufficient in some rodent species. Human genetic diseases such as Werner's
      syndrome indicate that the duration of the life span is also genetically
      regulated, and is independent of the cessation of cell proliferation.

PMID- 9524755
TI  - Human ageing and telomeres.
AB  - Telomerase expression is repressed early in development in all normal somatic
      human tissues investigated to date, whereas activity and the expression of the
      RNA component for this enzyme are upregulated in almost all cases of malignant
      transformation and late-stage cancer. The telomere hypothesis of ageing and
      immortalization postulates that sufficient telomere loss on one or more
      chromosomes in normal somatic cells triggers cell senescence, whereas
      reactivation of the enzyme is necessary for cell immortalization. Measurements of
      telomere length and telomerase activity in cancer and during normal and
      accelerated human ageing in skin, blood, haemopoietic, skeletal muscle, vascular
      and CNS tissues support this model. Tissue culture studies of cell ageing and
      transformation have added to our understanding of telomere dynamics in these
      processes. Evolution of telomerase repression and mortality in somatic cells of
      long-lived organisms is consistent with antagonistic pleiotropy models in which
      cell senescence is a tumour suppressor mechanism: stringent repression of
      telomerase has a beneficial early effect in reducing the probability of cancer,
      but a deleterious, unselected late effect in its contributions to age-related
      disease.

PMID- 9524756
TI  - Telomerase assays in the diagnosis and prognosis of cancer.
AB  - Telomerase activity is present in most primary human tumours but not in normal
      somatic tissues except for proliferative cells of renewal tissues (e.g. crypts of
      the intestine, basal layer of the epidermis, haemopoietic and inflammatory
      cells). In some instances telomerase activity is detected in preinvasive lesions,
      whereas in others it is only detected at later stages. Lower telomerase activity
      levels are detected in some specimens obtained from regions adjacent to primary
      tumours. The key clinical challenge is to determine if the presence or level of
      telomerase activity has diagnostic or prognostic utility. Almost any clinical
      specimen can be used to assay telomerase activity including frozen sections, fine
      needle aspirates, brushes, washes and sedimented cells in voided urine. In
      certain cancers increased telomerase activity levels may identify patients that
      will have either favourable or poor prognostic outcomes, whereas in other
      instances telomerase activity can distinguish between benign and malignant
      lesions. New approaches to improve the diagnostic value of telomerase
      determinations include application of in situ hybridization methods for detecting
      human telomerase RNA expression on archival paraffin-embedded material. Results
      show that this assay easily distinguishes cancer from normal cells, and thus may
      complement the telomerase activity assays.

PMID- 9524757
TI  - Mouse models for the study of telomerase.
AB  - The ends of chromosomes, or telomeres, consist of short repeated sequences that
      are synthesized by a ribonucleoprotein-DNA polymerase called telomerase. The RNA
      component of telomerase is essential for enzyme activity. The maintenance of
      telomere length by telomerase has been proposed to be essential for cellular
      viability and to play an important role in cellular senescence and
      immortalization. We are interested in using the mouse as a model system for the
      study of telomerase. We studied telomerase activity and expression of the mouse
      telomerase RNA component (mTR) in two different transgenic mouse models of
      multistage tumorigenesis: models of islet cell carcinoma and squamous cell
      carcinoma. In both tumour models, telomerase activity was detected only in late
      stage tumours, whereas the telomerase RNA was present at higher than normal
      levels in pre-neoplastic stages and increased further in late-stage tumours.
      However, the RNA levels did not parallel the amounts of telomerase activity
      detected, suggesting that regulation of telomerase activity does not correlate
      with the regulation of its RNA component. These results establish a direct
      correlation between progression to late-stage tumours and induction of telomerase
      activity, and suggest that the initial upregulation of telomerase RNA is an early
      event. To address the role of telomerase during normal mouse development and
      tumour formation, we have constructed a knockout mouse for the mouse telomerase
      RNA, mTR-/-. These mice and the cell lines derived from them are telomerase
      deficient.

PMID- 9524758
TI  - Genetic control of telomerase and replicative senescence in human and rodent
      cells.
AB  - The ribonucleoprotein telomerase is detectable in most human cancer cells and
      immortalized cells but is absent or inactive in the vast majority of normal
      counterparts. Repression of telomerase activity in human somatic cells, which
      leads to telomere shortening and replicative senescence, may have evolved as a
      protective mechanism against immortalization, unfettered clonal evolution and
      cancer. Rodent cells in culture are far more susceptible to immortalization and
      malignant progression than human cells. This can be explained by our observation
      that normal diploid rodent (hamster) fibroblasts possess active telomerase
      throughout their proliferative life span, and therefore they do not require a
      telomerase activation step during immortalization. Monochromosome transfer
      techniques have enabled us to identify powerful telomerase repressive activity
      specifically associated with the introduction of a single copy of human
      chromosome 3 into human carcinoma cells. Fine-structure deletion analysis of non
      repressed hybrids has permitted us to map the position of the candidate
      telomerase repressor gene to 3p21.1-3p21.3. A strategy for isolating the gene has
      been developed involving a combination of fine-structure deletion mapping and
      functional gene transfer approaches. The availability of cloned telomerase
      repressor genes will advance our understanding of telomerase regulation in the
      human soma and its disruption during human cancer development.

PMID- 9524759
TI  - Repair and processing events at DNA ends.
AB  - Cell nuclei contain several abundant enzymes that bind rapidly and avidly to
      exposed termini of DNA. The properties and physiological roles of such factors
      are described; they include poly (ADP-ribose) polymerase, DNA-dependent protein
      kinase, several DNA ligases and excision-repair enzymes. Telomeres normally seem
      shielded from these activities by telomere-binding proteins. If incomplete
      protection of telomeres occurred, the functions of the DNA end-specific enzymes
      would be relevant for processing of telomeres. This could include alternative
      pathways for telomere propagation in telomerase-negative cells.

PMID- 9524760
TI  - Telomeres in the haemopoietic system.
AB  - The limited life span of most blood cells requires the continuous production of
      cells, which in adults exceeds 10(12) cells/day. This impressive production of
      cells (approximately 4 x 10(16) cells over a lifetime) is achieved by the
      proliferation and differentiation of committed progenitor cells, which themselves
      are derived from a population of pluripotent stem cells with self-renewal
      potential. Paradoxically, the large majority of stem cells in adult bone marrow
      are quiescent cells. One possibility is that stem cells, like other somatic
      cells, have only a limited replicative potential (< 100 divisions). This
      hypothesis is supported by two key observations and the consideration that, in
      theory, 55 divisions can yield 4 x 10(16) cells. First, it was shown that
      'candidate' stem cells purified from fetal and adult tissue showed dramatic
      functional differences in turn-over time and the ability to produce cells with
      stem cell properties, Second, these functional differences were found to
      correlate with a measurable loss of telomere repeats despite the presence of low
      but readily detectable levels of telomerase in all purified cell fractions. In
      order to address questions about the role of telomeres in normal and malignant
      haemopoiesis, we developed a quantitative fluorescence in situ hybridization
      technique. Here we review the characteristics of this novel tool to assess the
      number of telomere repeats at the end of individual chromosomes and provide an
      overview of recent observations.

PMID- 9524761
TI  - Evolution of vertebrate fibrin formation and the process of its dissolution.
AB  - The thrombin-catalysed conversion of fibrinogen into a fibrin gel is common to
      all extant vertebrates. Because fibrin formation is both temporary and risky, an
      effective scheme for fibrinolysis evolved concomitantly. In this regard, the
      fibrinogen molecule is well adapted both for network polymerization and for
      subsequent dismantling. The question is, has it always been so? It has long been
      known that the three non-identical chains that compose vertebrate fibrinogen are
      descended from a common ancestor, and the original molecule must have been either
      a homotrimer or a dimer thereof. Three-dimensional studies on core fragments of
      fibrinogen are revealing new insights about both fibrin formation and its
      destruction. These studies are also showing exactly what structural changes have
      accompanied changes in function for the various domains. Chief among these is the
      reversal of direction for the alpha chain after replacement of its C-terminal
      domain.

PMID- 9524763
TI  - The kringle domains of human plasminogen.
AB  - The mature form of the zymogen, human plasminogen (HPlg), contains 791 amino
      acids present in a single polypeptide chain. The fibrinolytic enzyme, human
      plasmin (HPlm), is formed from HPlg as a result of activator-catalysed cleavage
      of the Arg561-Val562 peptide bond in HPlg. The resulting HPlm contains a heavy
      chain of 561 amino acid residues, originating from the N-terminus of HPlg, doubly
      disulfide-linked to a light chain of 230 amino acid residues. This latter region,
      containing the C-terminus of HPlg, is homologous to serine proteases such as
      trypsin and elastase. The heavy chain of HPlm consists of five repeating triple
      disulfide-linked peptide regions, c. 80 amino acid residues in length, termed
      kringles (K), that are responsible for interactions of HPlg and HPlm with
      substrates, inhibitors and regulators of HPlg activation. Important among the
      ligands of the kringles are positive activation effectors, typified by lysine and
      its analogues, and negative activation effectors, such as Cl-. The kringle
      domains of HPlg that participate in these binding interactions are K1, K4 and K5,
      and perhaps K2. These modules appear to function as independent domains. The
      amino acid residues important in these kringle/ligand binding interactions have
      been proposed by structural determinations, and their relative importance
      quantified by site-directed mutagenesis experimentation.

PMID- 9524762
TI  - Evolution of plasminogen-related growth factors (HGF/SF and HGF1/MSP).
AB  - HGF/SF and HGF1/MSP define a novel growth factor family whose members share the
      domain structure and the proteolytic process of activation of the blood
      proteinase precursor plasminogen. The amino acid and RNA sequences of HGF/SF and
      HGF1/MSP, the intron-exon organization of their genes and the predicted 3D
      structure of individual domains indicate that HGF/SF and HGF1/MSP evolved along
      with plasminogen and other members of the kringle-serine proteinase (KSP)
      superfamily from an ancestral gene that contained a single copy of the kringle
      domain, a serine proteinase domain and an activation peptide connecting the two
      domains. A series of intragenic duplications of the kringle domain, gene
      duplications, exon shuffling and deletions is responsible for the genes currently
      present in mammals, avians and amphibians. Plasminogen, HGF/SF and HGF1/MSP
      represent paradigmatic examples of the modern, multi-domain proteins typically
      associated with vertebrate organisms and illustrate a novel evolutionary pathway
      that led to the emergence of molecules with growth regulatory activity from
      proteolytic enzymes.

PMID- 9524764
TI  - Structure and function of microplasminogen: reconstitution of microplasminogen
      and microplasmin from isolated fragments.
AB  - We describe limited chemical proteolysis of microplasminogen/microplasmin
      (mPlg/mPlm) and their reconstitution from isolated fragments. A V141-->M141
      substitution in methionineless human mPlg/mPlm allowed the protein(s) to be
      cleaved in CNBr/formic acid. The resulting two fragments (141 and 118 residues,
      respectively), each internally disulfide bonded, were separated by preparative
      non-reducing gradient SDS-PAGE, and could then be mixed to reconstitute the
      characteristic mPlg/mPlm, including their activation by urokinase (uPA) and
      streptokinase (SK), and inhibition by macromolecular inhibitors. The isolated
      larger, N-terminal fragment, which contains the mPlg activation site in a normal
      disulfide configuration, was not cleaved by uPA in the absence of its smaller C
      terminal companion, showing that the linear amino acid sequence is not by itself
      sufficient to confer substrate character, even when its conformation is
      constrained by the disulfide structure.

PMID- 9524765
TI  - Domain structure of hepatocyte growth factor/scatter factor (HGF/SF).
AB  - The modular structure of hepatocyte growth factor/scatter factor (HGF/SF) has
      facilitated structure-function analysis. Domain deletion experiments have
      established that the N-domain, kringle 1 and kringle 2 are essential for HGF/SF
      activity on target cells and that, conversely, truncated variants containing the
      N-domain and kringle 1 (NK1) or kringles 1 and 2 (NK2) exhibit partial agonistic
      or antagonistic activity depending on target cells and the presence of full
      length HGF/SF. The 3D structures of the six domains of HGF/SF have been modelled
      on the structure of homologues, offering interesting insights into putative
      mechanisms of domain interactions, receptor binding and activation. The
      predictions offered by such models are currently assessed by protein engineering
      techniques and will ultimately be measured against experimental structures.

PMID- 9524766
TI  - Plasminogen/plasminogen activator and growth factor activation.
AB  - The plasminogen/plasminogen activator system is widely used in extracellular
      proteolysis. In this review the involvement of this system in tumour invasion,
      cell migration, growth factor presentation and inhibition of angiogenesis are
      discussed.

PMID- 9524767
TI  - Met-HGF/SF: tumorigenesis, invasion and metastasis.
AB  - Hepatocyte growth factor/scatter factor (HGF/SF) is synthesized by mesenchymal
      cells and is a paracrine effector of cells, predominantly epithelial, that
      express the Met tyrosine kinase receptor. We have demonstrated that autocrine Met
      HGF/SF expression in mouse fibroblasts results in transformation and
      tumorigenesis. HGF/SF-treated cells expressing Met can respond in a variety of
      ways: mitogenically, by scattering (motility), and by forming branching tubules
      in gel matrices (branching morphogenesis). HGF/SF also induces in vitro
      invasiveness and is angiogenic in in vivo assays. A human cell line and several
      mouse cell lines that we have constructed to express Met-HGF/SF in an autocrine
      fashion are tumorigenic, invasive and metastatic in athymic nude mice. Thus, the
      very complex process of invasion and metastasis can be mediated by a ligand
      receptor signalling pathway, and the cell lines we have developed provide
      important model systems for identifying the signalling molecules that mediate
      these phenotypes: For example Met-HGF/SF signalling activates the urokinase
      plasminogen proteolysis network, thus coupling this signal transduction pathway
      to the proteases that mediate dissolution of the extracellular matrix. Branching
      morphogenesis, mediated by Met-HGF/SF signalling, is dependent on this process,
      as well as the formation of cell-cell junctions and interaction with the
      extracellular matrix. We have proposed a hypothesis for the role of Met and
      downstream signalling molecules in generating normal ducts and lumenal
      structures, as well as a model for how interruption of this signalling leads to
      abnormal malignant progression. Is Met involved in human cancer? Human sarcomas
      often inappropriately express Met, suggesting that it is an important oncogene in
      these cancers, and an increasing number of reports have implicated Met-HGF/SF
      signalling in a variety of human cancers.

PMID- 9524768
TI  - Scatter factor receptors are key players in a unique multistep program leading to
      invasive growth.
AB  - Hepatocyte growth factor/scatter factor (HGF/SF) is the prototype of a family of
      structurally related soluble molecules (scatter factors) which also includes the
      HGF-like/macrophage-stimulating protein (HGF1/MSP). HGF/SF and HGF1/MSP control a
      complex genetic program known as 'invasive growth' which leads to cell
      dissociation, proliferation, invasion of extracellular matrix, prevention of
      apoptosis, acquisition of polarity and tubule formation. The HGF/SF and HGF1/MSP
      receptors are the tyrosine kinases encoded by the homologous genes met and ron.
      During development coordinated control of invasive growth by HGF-Met is
      essential. Met and Ron receptor signalling occurs via a two-phosphotyrosine
      multifunctional docking site located in their C-terminal regions. Activation of
      Ras and phosphatidylinositol-3-kinase through the multifunctional docking site is
      required for receptor-mediated invasive growth. In a number of malignant tumours
      met and ron are mutated, amplified or overexpressed. Oncogenically activated met
      and ron confer transforming, invasive and metastatic properties to normal cells.
      Point mutations of the multifunctional docking site dissociate the transforming
      potential from the invasive-metastatic phenotype showing that distinct signalling
      pathways are involved. This review summarizes the recent progress made in
      understanding the signalling mechanisms initiated by the scatter factor receptors
      leading to invasive growth.

PMID- 9524769
TI  - Competence for neural induction: HGF/SF, HGF1/MSP and the c-Met receptor.
AB  - During the early stages of development of the vertebrate embryo, the nervous
      system is induced by a special region, Hensen's node (or 'organizer'), situated
      at the tip of the primitive streak during gastrulation. Neural induction is
      finely regulated both by the timing of inducing signals emitted by the organizer
      and by temporal and spatial changes in the responsiveness of the ectoderm
      ('competence'). Here we review the evidence that the glycoprotein L5-220 is a
      marker for competent cells, that it is involved directly in the response to
      neural inducing signals, and that its expression, as well as competence itself,
      are maintained and enhanced by HGF/SF. HGF/SF is expressed in the node itself,
      suggesting that the organizer maintains the responsiveness of neighbouring
      regions to inducing signals. We also speculate that HGF1/MSP may play a role in
      setting up the initial competent region at earlier stages of development.

PMID- 9524770
TI  - The functions of HGF/SF and its receptor, the c-Met tyrosine kinase, in mammalian
      development.
AB  - Hepatocyte growth factor/scatter factor (HGF/SF) can induce epithelial
      mesenchymal conversion of epithelial cells in culture, with the dissociated cells
      becoming highly motile. The signal given by HGF/SF is mediated by its specific
      receptor, the c-Met tyrosine kinase. Targeted mutations in the mouse have
      demonstrated that HGF/SF and c-Met take over functions in development of the
      placenta, liver and skeletal muscle. During development of skeletal muscle, the
      receptor and its ligand control migration of myogenic precursor cells in the
      embryo. These myogenic precursors undergo an epithelial-mesenchymal conversion
      and detach from the dermomyotome of the somite. They then migrate to different
      sites in the embryo where they terminally differentiate to form skeletal muscle.
      Mutations in the HGF/SF or c-met genes abolish emigration of myogenic precursor
      cells. As a consequence, skeletal muscle groups that derive from migrating cells
      do not form. Ectopic application of HGF/SF in the chick embryo induces epithelial
      mesenchymal conversion and emigration of dermomyotomal cells. Moreover, the
      expression patterns of HGF/SF and c-Met in the mouse embryo are in accordance
      with a function of HGF/SF in the induction of epithelial-mesenchymal conversion
      and the generation of migrating myogenic precursor cells in vivo. The pattern
      suggests additional roles during the migratory process, which will be discussed.

PMID- 9524771
TI  - Biological aspects of macrophage-stimulating protein (MSP) and its receptor.
AB  - Macrophage-stimulating protein (MSP; also known as HGF-like protein [HGFl]) is a
      78 kDa plasma protein that is secreted by the liver into the circulation as
      single-chain, biologically inactive pro-MSP. The presence of conserved triple
      disulfide loops (kringles) places pro-MSP in a family of coagulation system
      serine protease zymogens that are activated by proteolytic cleavage. Although pro
      MSP has lost enzymic activity, it has retained the activation mechanism, in that
      proteolytic cleavage at a single site yields biologically active disulfide-linked
      alpha beta-chain heterodimeric MSP. The MSP receptor is a transmembrane protein
      tyrosine kinase. MSP causes phosphorylation of the receptor cytoplasmic domain,
      association of phosphatidylinositol (PI)-3 kinase with the receptor, and
      phosphorylation of receptor-bound PI-3 kinase. Inhibition of PI-3 kinase by
      wortmannin prevents MSP action on cells. MSP stimulates motility of murine
      resident peritoneal macrophages. However, it does not act on exudate macrophages
      or blood monocytes, since these earlier maturational stages of the lineage do not
      express the receptor. MSP also stimulates keratinocyte cell lines, causing either
      chemotactic responses or increased cell numbers in culture. We suggest that pro
      MSP diffuses into local tissue sites, where proteolytic cleavage to MSP results
      in stimulation of keratinocytes and macrophages. It possibly plays a role in
      tissue injury or wound healing.

PMID- 9524772
TI  - HGF: its organotrophic role and therapeutic potential.
AB  - Hepatocyte growth factor (HGF), originally implicated as a long-sought after
      hepatotrophic factor, supports epithelial branching duct formation in the
      developing lung as, a mesenchymal-derived morphogen. HGF elicits a potent
      organotrophic function for regeneration of organs including the liver, kidney and
      lung, through epithelial-stromal interactions. It prevents the onset or progress
      of hepatic fibrosis/cirrhosis, as well as the accompanying severe hepatic
      failure, and may become an effective drug for the treatment of fatty liver. HGF
      prevents the onset of acute and chronic renal failure, acts as pulmotrophic
      factor which enhances lung regeneration, and suppresses the onset of lung
      fibrosis. HGF may also be effective for treatment of vascular diseases, gastric
      ulcers, diabetes mellitus and neuronal diseases. Our results provide a new
      therapeutic strategy for treating such diseases.

PMID- 9524773
TI  - HGF/SF in angiogenesis.
AB  - Hepatocyte growth factor/scatter factor (HGF/SF) is a mesenchyme-derived cytokine
      that stimulates motility and invasiveness of epithelial and cancer cells. These
      responses are transduced through the c-met proto-oncogene product, a
      transmembrane tyrosine kinase that functions as the HGF/SF receptor. We have
      shown that HGF/SF is a potent angiogenic molecule and that its angiogenic
      activity is mediated primarily through direct actions on vascular endothelial
      cells. These include stimulation of cell migration, proliferation, protease
      production, invasion, and organization into capillary-like tubes. We further
      showed that HGF/SF is overexpressed in invasive human cancers, including breast
      cancer, relative to non-invasive cancers and benign conditions. In invasive
      breast cancers, the content of HGF/SF is strongly correlated with that of von
      Willebrand's factor, a marker of vascular endothelial cells. Furthermore,
      transfection of breast cancer and glioma cell lines with HGF/SF cDNA greatly
      enhanced the ability of these cells to grow as tumours in orthotopic sites in
      syngeneic or immunocompromized host animals. The increased growth rate of the
      HGF/SF-transfected cells was attributable, in part, to increased tumour
      angiogenesis. These findings suggest that HGF/SF may function as a tumour
      progression factor, in part by stimulating tumour cell invasiveness and in part
      by stimulating angiogenesis.

PMID- 9524774
TI  - Role of HGF/SF and c-Met in morphogenesis and metastasis of epithelial cells.
AB  - We have analysed the role of hepatocyte growth factor/scatter factor (HGF/SF) in
      the process of morphogenesis and metastasis of epithelial (carcinoma) cells.
      HGF/SF induces various morphogenic responses in epithelial cells that derive from
      different tissues when these are grown in three-dimensional gels, e.g. branching
      tubules in kidney, breast, and prostate epithelial cells, crypt-like structures
      with brush border in colon epithelial cells, and alveolar-like aggregates in lung
      and pancreas cells. Epithelial cells are thus able to form complex structures in
      vitro which resemble the structures formed in the organ they originate from. We
      also examined the response of human breast carcinoma cells to HGF/SF in vivo. MDA
      MB 435 cells transfected with HGF/SF were injected into the mammary fat pad of
      nude mice, where they form tumours which spontaneously metastasize to the lungs.
      We found that expression of HGF/SF promoted metastasis whereas expression of the
      cell adhesion molecule E-cadherin was inhibitory. Moreover, expression of E
      cadherin reconstituted the ability of the cells to form complex structures in
      response to HGF/SF in vitro. These data demonstrate that the different responses
      to HGF/SF depend on the state of the epithelial cells: morphogenesis requires
      epithelial differentiation and cell polarity, whereas metastasis is observed when
      the cells have lost their epithelial characteristics. Moreover, we have recently
      identified Gab-1 as a direct-binding substrate of the c-Met receptor. Gab-1 binds
      to c-Met phosphorylated on tyrosine residues, but not to a number of other
      tyrosine kinases from different subfamilies. A newly identified proline-rich
      domain of Gab-1 is responsible for the binding to the bidentate docking site in c
      Met. Expression of Gab-1 in epithelial cells is sufficient to induce c-Met
      specific cellular responses which include the formation of branching tubules.
      Thus, Gab-1 seem to correspond to the substrate of the c-Met receptor tyrosine
      kinase that mediates the epithelial morphogenesis.

PMID- 9524775
TI  - Demonstration of DNA replication factor C in human glomerular lesions.
AB  - Glomerulosclerosis is a common pathological finding in many human glomerular
      diseases that ultimately leads to end-stage kidney disease. The regulatory
      mechanism that controls mesangial proliferation as well as accumulation of
      mesangial matrix, however, is not known. Recently, a protein factor (MSW) which
      binds to the specific sequence of the promoter of the alpha 1 and alpha 2 type IV
      collagen genes was cloned. MSW was found to be identical to a large subunit
      (Alp145) of DNA replication factor C. These findings suggest that MSW may have
      important functions in mesangial cell proliferation and type IV collagen
      synthesis, both of which are prominent findings in glomerulosclerosis. In the
      present study, we report that augmented expression of MSW protein in human
      glomerular diseases that exhibit glomerulosclerosis (IgA nephropathy,
      membranoproliferative glomerulonephritis, and focal glomerulosclerosis). Minimal
      expression of MSW protein was observed in human glomerular diseases that rarely
      show glomerulosclerosis (membranous nephropathy, and minimal change nephrotic
      syndrome). There was a significant correlation between the levels of MSW
      expression and type IV collagen expression. Elevated expressions of both
      proliferating cell nuclear antigen and MSW were also observed in most patients
      with proliferative glomerular diseases. These studies suggest that MSW protein
      plays a regulatory role in the development of mesangial cell proliferation and
      matrix expansion during progression of glomerular injuries.

PMID- 9524776
TI  - Expression of cell adhesion molecules in tubulointerstitial nephritis associated
      with Sjogren's syndrome.
AB  - The tissue distribution of cellular adhesion molecules (ICAM-1, ELAM-1, VCAM-1)
      was studied in specimens from six normal human kidneys and in six biopsies from
      kidneys with tubulointerstitial nephritis associated with Sjogren's syndrome. In
      addition, the expression of cellular adhesion molecules was examined both in four
      renal biopsies from cases of tubulointerstitial nephritis of diverse pathogenesis
      and in six lip biopsies from cases of Sjogren's syndrome. ICAM-1 was expressed on
      vascular endothelial cells in normal kidneys, in all specimens of
      tubulointerstitial nephritis and in salivary glands. On tubular epithelial cells,
      ICAM-1 appeared slightly in normal kidneys; otherwise tubular epithelial ICAM-1
      was observed in and around the foci of cellular infiltration in all cases of
      tubulointerstitial nephritis. ELAM-1 and VCAM-1 were observed on the newly
      generated vessels in massive cellular infiltrates in some cases of
      tubulointerstitial nephritis associated with Sjogren's syndrome; by contrast,
      they were not seen in normal kidneys and in cases of tubulointerstitial nephritis
      of diverse pathogenesis. In the lip biopsies from salivary glands, ICAM-1 was
      observed on ductal epithelial cells in and around the foci of cellular
      infiltration, and ELAM-1 and VCAM-1 occasionally appeared on the newly generated
      vessels in massive cellular infiltrates. Chronic and progressive inflammation may
      be facilitated by such ELAM-1 and VCAM-1 expression on newly generated vessels.
      The adhesion molecules were thought to play a role in the pathogenesis of
      tubulointerstitial nephritis and sialoadenitis associated with Sjogren's
      syndrome. It was thus concluded that the same inflammatory process that took
      place in the salivary glands to induce the characteristic tissue change of
      Sjogren's syndrome likely was operative in the renal tubulointerstitial tissue as
      well.

PMID- 9524777
TI  - Recurrence of renal disease after kidney transplantation in children: 24 years of
      experience in a single center.
AB  - The aim of this study was to assess the frequency and clinical implications of a
      recurrence of the original renal disease in children after kidney
      transplantation. Thus, the records of patients with immunological and metabolic
      diseases transplanted between 1970 and 1994 were retrospectively analyzed. There
      were 113 renal transplantations in 99 patients, who had the following original
      diseases: focal segmental glomerulosclerosis (FSGS), membrano-proliferative
      glomerulonephritis type I and type II (MPGN I, II), Henoch-Schoenlein nephritis,
      IgA-nephropathy, hemolytic uremic syndrome (HUS) and hyperoxaluria type I (PH I)
      and other rare diseases. Recurrences were observed in FSGS, MPGN II, HUS and PH I
      but not in the other diseases. In FSGS, the recurrence rate was 20% with graft
      failure in 5 of 6 grafts. No specific risk factors for recurrent FSGS could be
      determined. In MPGN II, the recurrence was 60% but the loss of grafts occurred at
      the same rate as in the non-recurrence group. In HUS, recurrence was seen in 4
      out of 24 renal grafts (16.6%) with subsequent graft loss in all cases. All cases
      had suffered from an atypical HUS. PH I recurred in 4 of 5 allografts with graft
      loss in all patients. The remaining graft was transplanted after a liver
      transplantation and graft function was well preserved for 4 years. We confirm
      that the risk of recurrence with loss of the graft is high in a certain group of
      renal diseases. In these the indication for transplantation, particularly with
      living related donor kidneys, needs special evaluation. A better understanding of
      the pathomechanism of the diseases should lead to prevention of recurrence, as in
      PH I in which a liver transplant is now the primary option.

PMID- 9524778
TI  - A review of acute renal failure in children: incidence, etiology and outcome.
AB  - We reviewed our experience of children with acute renal failure. St James's
      University Hospital, Leeds, UK is a tertiary referral center that serves a
      relatively stable regional population (former Yorkshire region). It is a mixed
      rural and urban population providing a unique profile of the nature of the cases
      and workload experienced. The data is expressed as a function of age and compared
      against a previous era of paediatric nephrology and current adult incidence data.
      Over an 8-year period (1984-1991) 227 children were referred for dialysis
      management of acute renal failure. The yearly incidence was 0.8 per 100,000 total
      population. Acute renal failure in the child population was almost a fifth of the
      adult incidence. Age-related incidence however shows the highest incidence in the
      neonate/infant population and is comparable to adult data. The intensive care
      unit was needed for nearly half the children. For all ages hemolytic uremic
      syndrome was the commonest cause (45%). Surgery for congenital heart disease was
      predominant (63%) in the neonate group. The overall mortality was 25%. Primary
      renal disease accounts for only 7% of the etiologies and was the source for the
      majority that went on to require chronic renal replacement therapy. Acute renal
      failure is nearly always a secondary event in the face of other organ failure and
      the majority of the mortality arises from surgery for congenital heart disease.
      If the underlying condition is treatable, the prognosis for recovery from acute
      renal failure with appropriate supportive care is excellent.

PMID- 9524779
TI  - Predictors of prognosis and risk of acute renal failure in bacterial
      endocarditis.
AB  - BACKGROUND: The epidemiology, criteria for diagnosis and treatment of bacterial
      endocarditis has changed substantially in the past 2 decades, yet little
      attention has been given to the changing etiologies of renal insufficiency and
      the predictors of renal failure or the relationship between renal failure and
      mortality in patients with bacterial endocarditis. OBJECTIVE: To study the risk
      factors for the development of acute renal failure and death among patients with
      definite bacterial endocarditis. SETTING: Tertiary referral university medical
      center. METHODS: Retrospective chart review of 204 consecutive episodes of
      definite bacterial endocarditis as defined by the Duke criteria. Logistic
      regression was used to identify clinical and biochemical predictors of death and
      the development of acute renal failure. RESULTS: Two hundred and four episodes of
      endocarditis identified in 185 patients were evaluated. The overall mortality for
      the group was 20%. The presence of prosthetic valve endocarditis and
      thrombocytopenia was associated with increased risk of death in hospital. One
      third of the patients developed acute renal failure (defined as a serum Cr of 2
      mg/dl or above). The presence of acute renal failure increased the odds (OR) of
      dying by 5 (p = 0.0001). Clinical and biochemical variables at presentation that
      were significantly associated by univariate analysis with the risk of developing
      acute renal failure were: increased age, a history of hypertension,
      thrombocytopenia, the presence of Staphylococcus aureus, and prosthetic valve
      infection. Age (OR 2.9, p = 0.002) and the degree of thrombocytopenia (OR 0.2, p
      = 0.0001) were independently associated with an increased risk of developing
      acute renal failure. Patients who developed acute renal failure as a result of
      septic syndrome or following cardiac surgery had a higher mortality when compared
      to other causes of acute renal failure. CONCLUSION: Acute renal failure
      associated with bacterial endocarditis remains a frequent clinical problem that
      is often associated with a fatal outcome. Patients with increased age, and the
      degree of thrombocytopenia were independent risk factors for developing acute
      renal failure.

PMID- 9524780
TI  - Heart rate variability and n-3 fatty acids in patients with chronic renal failure
      -a pilot study.
AB  - Patients with chronic renal failure (CRF) often have autonomic cardiac
      dysfunction, which can be assessed by measuring heart rate variability (HRV).
      This dysfunction prediposes the patients to sudden cardiac death. This study
      describes 24-hour HRV in patients with CRF compared to HRV in patients with a
      previous myocardial infarction (MI). Furthermore, associations between HRV in
      patients with CRF and the content of n-3 polyunsaturated fatty acids (PUFA) in
      cell membranes were examined, because n-3 PUFA may improve HRV. Twenty-nine
      patients with CRF treated with dialysis were enrolled. A 24-hour Holter recording
      was obtained at baseline and the HRV variables, RR (= mean of all normal RR
      intervals during the 24-hour recording) and SDNN (= standard deviation of all
      normal RR intervals in the entire 24-hour recording) were analyzed. Also,
      granulocyte fatty acid composition was determined. The patients were allocated to
      dietary supplementation with either 5.2 g of n-3 PUFA or a placebo oil (olive
      oil) daily for 12 weeks in a double-blind design. At the end of the
      supplementation period the Holter recording and blood sampling were repeated. At
      baseline the CRF patients' mean SDNN ws 86 ms compared to 118 ms (p < 0.01) in
      patients with a previous MI. After supplementation with either n-3 PUFA or
      placebo a highly significant correlation was observed between the content of n-3
      PUFA in cell membranes and HRV (r = 0.71, p < 0.01). Furthermore, when the
      patients were dichotomized according to their mean SDNN, it was found, that those
      with the highest SDNN had a higher content of n-3 PUFA in cell membranes compared
      to those with the lowest SDNN (7.8% vs 4.2%, p < 0.05). In conclusion, HRV was
      decreased in CRF patients indicating a cardiovascular autonomic dysfunction. The
      positive correlation between the n-3 PUFA content in cell membranes and HRV
      suggests that the effects of an increased intake of n-3 PUFA in CRF patients
      should be further studied.

PMID- 9524781
TI  - Gender differences in mediators of left ventricular hypertrophy in dialysis
      patients.
AB  - Left ventricular hypertrophy (LVH) is known to be a strong predictor of
      cardiovascular death in dialysis patients, but the mediators for its development
      remain to be clarified. In the non-renal population risk factors for LVH differ
      between the genders. We therefore studied 46 non-diabetic patients (26 male, 19
      female) on maintenance hemodialysis (n = 25) or continuous ambulatory peritoneal
      dialysis (CAPD) (n = 20) all free from clinically evident cardiac disease, who
      underwent 48-hour ambulatory blood pressure (BP) monitoring, 2-D and M-mode
      echocardiography for left ventricular mass index (LVMI) and bloods for
      hemoglobin, parathyroid hormone (PTH), urea and electrolytes and liver function
      tests. Thirty-two out of 45 patients were taking antihypertensive drugs at the
      time of the study. The mean 48-hour BP was 135 +/- 19/83 +/- 13 mmHg and the mean
      LVMI was 144 +/- 50 g/m2. LVH (LVMI > 131 g/m2 men, > 100 g/m2 women) was present
      with equal frequency in both sexes: men 72% (18/25) and women 68% (13/19). Simple
      regression analysis showed that LVMI was correlated with 48-hour pulse pressure
      (r = 0.52, p < 0.00033), 48-hour systolic BP (r = 0.37, p < 0.05), PTH (r = 0.31,
      p < 0.04) and inversely with serum calcium (r = -0.29, p < 0.05) and hemoglobin
      (r = -0.33, p < 0.03). However, on multiple regression analysis pulse pressure
      (R2 = 28.7%), day systolic BP (R2 = 15.4%) and 48-hour systolic BP (R2 = 14.1%)
      were the only variables linked to LVMI. When the patients were split by gender,
      stepwise linear regression in the men showed a highly significant relationship
      between LVMI and pulse pressure (R2 = 37.1%) which was stronger at nighttime (R2
      = 42.6%), but in females this was not apparent (R2 = 4.39%) and indeed no
      variable was linked to LVMI. Our study confirms that LVH is not only prevalent in
      dialysis patients but is present with equal frequency in both sexes. However the
      determinants of its development are different for each gender. In males pulse
      pressure, and therefore by implication vascular compliance, is important but in
      females, other unidentified factors predominate.

PMID- 9524782
TI  - Calcium-PTH relationship in dialysis patients: the pitfalls of using a constant
      dialysate calcium concentration during the dynamic tests.
AB  - The calcium-PTH relationship in uremic patients has been often studied during
      dialysis sessions with high or low dialysate calcium concentration (CaD). This
      method has been used because it is less complex and invasive than i.v. infusion
      of calcium salts and calcium chelating agents. However, the constancy of CaD
      during the tests does not allow for the control of the serum calcium profile and,
      given that the blood calcium concentration is only one factor of a more complex
      calcium-related mechanism of the PTH release, the calcium-PTH curve may become
      dependent on the unpredictable rate at which the ionized calcium changes. Dynamic
      testing of the parathyroid gland was performed in 9 dialysis patients comparing
      constant CaD of 1.0 and 2.0 mmol/l (A) with a linear change in CaD (B). The rate
      of serum calcium change remained constant over time only in experiment B. The
      total decrease in calcemia (0-0.38 +/- 0.03 vs -0.14 +/- 0.1 mmol/l) and PTHmax
      (748.25 +/- 124.76 vs 374.89 +/- 53.03 pg/ml) were significantly higher in B,
      whereas the total increase in calcemia (+0.26 +/- 0.03 vs +0.28 +/- 0.02 mmol/l)
      and the minimum value of PTH (59.15 +/- 9.53 vs 55.64 +/- 9.08 pg/ml) were
      similar in both experiments. The calcium-PTH curves were clearly different in A
      and B. The setpoint and the slope were significantly higher in A (1.196 +/- 0.01
      vs 1.142 +/- 0.02 mmol/l; 840.54 +/- 96.85 vs 542.43 +/- 112.26%/mmol). For
      similar serum calcium values (1.084 +/- 0.01 vs 1.059 +/- 0.02 in the stimulation
      test and 1.325 +/- 0.02 vs 1.336 +/- 0.02 mmol/l in the inhibition test) the PTH
      secretion was significantly different (335.86 +/- 44.36 vs 647.65 +/- 104.09 in
      the stimulation test and 76.35 +/- 12.57 vs 105.03 +/- 20.59 pg/ml in the
      inhibition test). In conclusion, the way of inducing serum calcium change
      affected the calcium-PTH curve and the value of the set point and the slope was a
      function of the way in which the blood calcium changes were achieved. The
      modulated CaD dialysis was shown to be a more correct method of studying the
      calcium-PTH relationship in dialysis patients, as well as an alternative to the
      more complex and invasive infusional methodology.

PMID- 9524783
TI  - Evolution of IgA nephropathy into Henoch-Schoenlein purpura in an adult.
AB  - IgA nephropathy (IgAN) and Henoch-Schoenlein purpura (HSP) are clinically
      distinct conditions indistinguishable on renal biopsy. However, progression from
      IgAN to HSP has rarely been reported, particularly in adults. We report such a
      case: a young man with biopsy-proven IgAN and no systemic features of HSP who six
      years later developed classical HSP. This supports suggestions that the two
      conditions are different manifestations of the same disease.

PMID- 9524784
TI  - Recurrence of anti-GBM antibody disease twelve years after transplantation
      associated with de novo IgA nephropathy.
AB  - A patient developed recurrent anti-glomerular basement membrane (GBM) antibody
      (ab) disease after twelve years of an uneventful posttransplant course,
      clinically accompanied by rapidly rising creatinine. He additionally exhibited
      coexisting IgA nephropathy at the time of the reappearing anti-GBM disease. Both
      linear IgG and mesangial IgA were detected by immunofluorescence, and electron
      microscopy demonstrated mesangial immune complex deposits. To our knowledge, the
      association of anti-GBM ab disease and IgA nephropathy has not been reported
      previously.

PMID- 9524785
TI  - Rapidly progressive glomerulonephritis associated with hepatitis C virus
      infection.
AB  - Glomerular disease often accompanies a wide variety of liver diseases, including
      acute or chronic hepatitis. A striking association between hepatitis B virus and
      glomerulonephritis particularly membranous glomerulonephritis has been reported
      by various authors. It is not surprising, therefore, that hepatitis C virus (HCV)
      infection has been recently associated with the development of various types of
      glomerulonephritis. The principal type of glomerulonephritis associated with HCV
      infection is either cryoglobulinemic or non-cryoglobulinemic
      membranoproliferative glomerulonephritis. However, other types of glomerular
      lesions were seen in the clinical course of HCV infection. We report a rare case
      of a 20-year-old woman who developed rapidly progressive glomerulonephritis
      (RPGN) during the course of the active HCV infection. Whether this case
      represents a true association or a coincidental association is not known.

PMID- 9524786
TI  - Color Doppler imaging for detection of bleeding immediately following renal
      biopsy.

PMID- 9524787
TI  - Urinary N-acetyl-beta-glucosaminidase excretion in non-insulin-dependent diabetes
      mellitus: relation with diabetic nephropathy.

PMID- 9524788
TI  - Extreme swelling of a limb with A-V shunt for hemodialysis resulting from
      subclavian vein thrombosis due to previous catheterization.

PMID- 9524789
TI  - Treatment-resistant schizophrenia--the role of clozapine.
AB  - Treatment-resistant schizophrenia is the object of intense interest because of
      recent developments in its treatment and aetiology. The actual definition of
      treatment-resistant schizophrenia is, however, still controversial. It should
      reflect the legitimate and varied needs and perspectives of people with
      schizophrenia, their family members, mental health care givers, mental health
      administrators, public health officials, and those who fund the direct and
      indirect costs of treating schizophrenia. The most common definition of treatment
      resistant schizophrenia denotes patients with schizophrenia who, despite at least
      two adequate trials of classical neuroleptic drugs, have persistent moderate to
      severe positive, or disorganisation, or negative symptoms together with poor
      social and work function over a prolonged period of time. This definition
      reflects the viewpoint of people with this illness, their family members, and
      mental health care givers. Approximately 30% (range 10-45%) of schizophrenic
      patients meet these criteria. While this definition is adequate for many
      purposes, it should be realised that the remaining 70% of schizophrenic patients,
      whose positive symptoms respond adequately to neuroleptic treatment, may also
      have clinically significant negative symptoms, poor social and work function,
      clinically significant cognitive dysfunction, poor quality of life relative to
      the normal population, and constitute a significant burden to family and society.
      The lifetime suicide rate in both treatment-resistant and responsive
      schizophrenic patients is 9-13%, indicating that conventional definitions of
      neuroleptic response do not convey lower risk of suicide. However, before
      defining a patient as treatment resistant, it is important to consider whether
      the patient has received an inadequate duration of treatment, and/or too low, or
      possibly too high, doses of neuroleptic drugs. Using these stringent criteria,
      treatment resistance may be present at the time of initial diagnosis and
      treatment, but if not present initially, it will usually develop subsequently
      sometimes not until after multiple acute exacerbations over a period of years.
      During the first months and years after the diagnosis of schizophrenia has been
      made, clinicians should be especially alert in identifying a patient as treatment
      resistant in order to diminish the severe social disability and suicidality which
      may ensue if it is not recognised and correctly treated. Once present, treatment
      resistance is usually permanent. However, some treatment-resistant patients may
      again become responsive to treatment or undergo spontaneous remission of positive
      symptoms in later life. The treatment of patients with schizophrenia who are
      treatment resistant is generally much more expensive that that of neuroleptic
      responsive patients because their symptomatology and disturbed behaviour leads to
      more frequent and longer duration hospitalisations. Patients with treatment
      resistant schizophrenia may manifest one or more of the classical subtypes of
      schizophrenia which may differ biologically in terms of neurochemistry and
      structural brain abnormalities, e.g. ventricular enlargement. They usually have
      poorer premorbid function, an earlier age at onset of positive symptoms, are more
      likely to be male than female, and may have various quantitative types of
      cortical or ventricular abnormalities evident with computer tomography or
      magnetic resonance imaging scans. There are no established qualitative
      differences in cognitive dysfunction between the two groups of patients with
      schizophrenia, but cognitive impairment is more severe in treatment-resistant
      patients. Treatment-resistant schizophrenia does not usually respond to increased
      dosages of neuroleptic drugs, switching to other types of neuroleptics, or adding
      adjunctive agents such as benzodiazepines, antidepressants, anticonvulsants or
      lithium carbonate. (ABSTRACT TRUNCATED)

PMID- 9524790
TI  - Double-blind, randomised, placebo-controlled study of two concentrations of
      azelastine eye drops in seasonal allergic conjunctivitis or rhinoconjunctivitis.
AB  - This double-blind, randomised, placebo-controlled study was carried out to assess
      the efficacy and safety of 0.025% and 0.05% azelastine eye drops twice daily
      administered for 14 days to patients with seasonal allergic conjunctivitis or
      rhinoconjunctivitis. A total of 278 patients were recruited and 226 patients were
      evaluable for per protocol analysis. The target parameter was the response rate.
      Four eye symptoms, including the main symptom (itching) were recorded by patients
      in diaries and eight symptoms were assessed by physicians before and after seven
      and 14 days of treatment. Severity of symptoms was measured on a four-point
      scale. The response rates for itching (improvement of at least one score point
      within the first three days) according to patient assessment were 43% for
      placebo, 52% for 0.025% and 56% for 0.05% azelastine (NS). However, a more
      objective assessment of the three main eye symptoms by physicians showed a
      concentration-dependent improvement in response rate compared with placebo (a
      decrease of > or = 3 points from a baseline total score of > or = 6), which
      reached statistical significance for 0.05% azelastine on Day 7 (p < 0.002). In
      the evaluable patient population, the scores of the three main eye symptoms as
      well as of all eight recorded eye symptoms, as assessed by the physician, were
      significantly (p < 0.05) lower in the 0.05% azelastine eye drops group in
      comparison with the placebo group at Day 7. Inefficacy was the cause of
      withdrawal in five and three patients on 0.025% and 0.05% azelastine,
      respectively, and in six patients on placebo. Adverse drug effects, mainly a
      mild, transient irritation and a bitter or unpleasant taste, were reported by 14%
      (0.025%), 20% (0.05%) and 15% (placebo) of the patients. No serious side-effects
      occurred. Azelastine eye drops are effective and well tolerated at a
      concentration of 0.05% for the treatment of seasonal allergic conjunctivitis.

PMID- 9524791
TI  - Efficacy and tolerability of intramuscular and oral meloxicam in patients with
      acute lumbago: a comparison with intramuscular and oral piroxicam.
AB  - In this controlled, randomised, parallel-group, multicentre study, the efficacy
      and tolerability of an intramuscular (i.m.) dose of meloxicam (15 mg) on Day 1
      followed by seven days of oral meloxicam (15 mg/day) were compared with those of
      an i.m. dose of piroxicam (20 mg) on Day 1 followed by seven days of oral
      piroxicam (20 mg/day) therapy in a total of 169 outpatients with acute lumbago.
      Time to onset of analgesic action after i.m. injection was determined, and
      overall efficacy, pain on movement, limitation of daily activities, local
      tolerability at the injection site and overall tolerability were assessed by
      investigators and patients on verbal rating scales (VRSs). Adverse events and
      laboratory assessments were documented. Meloxicam and piroxicam showed a rapid
      onset of action after i.m. injection (40 and 45 minutes median time,
      respectively), overall efficacy of both therapies was highly rated, and
      limitations to daily life were greatly reduced in the majority of patients in
      both groups. There were no statistically significant differences in efficacy
      between meloxicam and piroxicam. Local and overall tolerabilities were equally
      good for the two drugs, but there were fewer gastrointestinal (GI) adverse events
      among meloxicam patients (1.2% of patients) than piroxicam patients (7.0% of
      patients). The improved tolerability profile of meloxicam may be explained by its
      selectivity towards cyclooxygenase-2.

PMID- 9524792
TI  - An open, controlled study of two non-absorbable antibiotics for the oral
      treatment of paediatric infectious diarrhoea.
AB  - Forty-nine children in need of antibacterial treatment for a severe episode of
      bacterial diarrhoea were consecutively treated with either an oral paediatric
      suspension of rifaximin (100 mg every six hours for an average of four days: 24
      patients), or paromomycin (125 mg every six hours for an average of four days: 25
      patients). Stools (number and form), enteritis symptoms and signs, and
      intolerance manifestations were all monitored on each day of treatment. A stool
      culture was performed on the first available stool after enrolment and after the
      end of treatment to monitor the drugs' antibacterial activity. A similar rate of
      bacteriological cure, with normalisation of stools and elimination of the
      clinical symptomatology, was attained by the two antibiotics, with statistical
      significance of changes vs. baseline being apparent on the second treatment day,
      in both treatment groups. Rifaximin results were quicker (treatment lasted three
      days in several cases) and on the whole slightly better (though without
      statistical significance) than those of paromomycin: 21/24 vs. 20/25 children
      were completely cured, with a failure rate of three and five cases, respectively.
      Systemic and local tolerance of both treatments were very good in all children.

PMID- 9524793
TI  - The effects of gentamicin on the activities of glutathione peroxidase and
      superoxide dismutase enzymes and malondialdehyde levels in heart tissues of
      guinea pigs.
AB  - In this study, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px)
      activities and malondialdehyde (MDA) levels were measured in heart tissues from
      guinea pigs treated with gentamicin and gentamicin plus vitamin E combination.
      Mean values were compared with those of the controls treated with only
      physiological saline solution. The activities of SOD and GSH-Px were found to be
      lower and the MDA level higher in the hearts from gentamicin-treated animals
      compared with those of the controls. In the gentamicin plus vitamin E group,
      however, tissue SOD activity was found to be increased and MDA level decreased
      significantly relative to the gentamicin group. GSH-Px activity was lowest in
      this group. Results suggest that gentamicin suppresses SOD and GSH-Px activities
      in heart tissue, thereby making the tissue more vulnerable to oxidative stress
      and peroxidative attacks, an important indicator of which is increased MDA level
      in the heart tissues from gentamicin-treated guinea pigs. This effect might be
      deleterious when gentamicin is used after cardiac surgery since a potential risk
      of free radical injury exists in the heart tissue during and/or after cardiac
      surgery owing to ischaemia and reperfusion processes, and, possibly, in the
      management of the patients with certain types of heart disease. Our results
      showed that vitamin E given concomitantly with gentamicin could protect the heart
      tissue against free radical injury.

PMID- 9524794
TI  - Cholesterol management in general practice.
AB  - Ninety general practitioners from the Fylde coast of Lancashire responded to a
      questionnaire regarding lipid management, revealing that only 22% aim for a
      target total cholesterol of < or = 5.2 mmol/l in patients with established
      ischaemic heart disease. One third are reassessing the cholesterol in these
      patients at yearly intervals or less frequently, and 36% select 65 years or less
      as the upper age limit for screening. Approximately 50% of GPs screen for
      hypercholesterolaemia in patients with cerebral or peripheral vascular disease.
      Primary screening and treatment of hypercholesterolaemia within the 'at risk'
      asymptomatic population is well established with 72% of GPs screening
      hypertensives, 88% screening diabetics and almost all screening patients with an
      adverse family history, but the therapeutic cholesterol targets vary widely
      between individual practitioners.

PMID- 9524795
TI  - Age at onset and regional cerebral glucose metabolism in Alzheimer's disease.
AB  - This study assessed 46 patients with Alzheimer's disease and 21 aged controls
      using positron emission tomography. Repeated analyses using a general linear
      model examined the effect of age at onset on the pattern of the regional cerebral
      metabolic rate of glucose (rCMRglc). The results showed significant age effects
      on the rCMRglc in the fronto-temporo-parietal association cortices and
      retrosplenial areas. Disease duration, overall cognitive severity or normal aging
      could not account for the effects. The age effects were delineated as a double
      dissociation, that is, early-onset patients have a more severe reduction of
      regional glucose metabolism in the association cortices, while late-onset
      patients show a more prominent metabolic deficit in the paralimbic area.

PMID- 9524796
TI  - Regional hypometabolism related to language disturbance in Alzheimer's disease.
AB  - To elucidate the nature of language disturbance in Alzheimer's disease (AD) and
      the cerebral area involved in it, we studied 65 AD patients with the Western
      Aphasia Battery (WAB) and with 18F-fluorodeoxyglucose and positron emission
      tomography. Partial correlations were evaluated between the Aphasia Quotient of
      WAB and regional cerebral glucose metabolism normalized by the mean metabolic
      rate in the bilateral primary sensorimotor areas after controlling age, sex,
      education and severity of illness. Language disturbance in AD is accounted for by
      deficits in the semantic processing of language and is related to glucose
      hypometabolism in the inferior temporal gyrus and inferior parietal lobule,
      especially in the dominant side. These results offer further evidence suggesting
      that the lexico-semantic processing system is mediated in these regions.

PMID- 9524797
TI  - Platelet monoamine oxidase B activity in dementia. A 4-year follow-up.
AB  - Platelet monoamine oxidase B (MAO-B) activity has been found to increase
      significantly in demented patients. For the first time, a 4-year follow-up of
      platelet MAO-B activity and Mini-Mental State (MMS) was performed in patients
      with probable dementia of the Alzheimer type (DAT) and age-matched controls. MAO
      B activity of DAT patients increased significantly 2 years after the beginning of
      the study as compared with controls and remained significantly higher for the
      entire period of the examinations (p < 0.0001). The decrease of the MMS scores
      did not correlate with the time course of the increase of platelet MAO-B activity
      (Spearman rank correlation test). The decline of the MMS scores of DAT patients
      preceded the elevation of MAO-B activity. Since degenerative processes in brain
      areas which are responsible for cognitive function and are reflected by the MMS
      scores rather affect cerebral cholinergic than monoaminergic neurotransmitter
      systems, degeneration of the latter at late stages of DAT might be reflected by
      increased platelet MAO-B activity.

PMID- 9524798
TI  - Further evidence of cholinergic impairment of the neuroendocrine control of the
      GH secretion in Down's syndrome.
AB  - There are data indicating that cholinergic activity is precociously impaired in
      Down's syndrome (DS). On the other hand, acetylcholine as well as arginine (ARG)
      play a major stimulatory role in the neural control of growth hormone (GH)
      secretion in humans, likely acting via the inhibition of hypothalamic
      somatostatin release. The aim of the present study was to verify the effects of
      pyridostigmine (PD, 120 mg p.o.), a cholinesterase inhibitor, and ARG (0.5 g/kg
      i.v.) on the growth hormone-releasing hormone (GHRH) (1 microgram/kg i.v.)
      induced GH rise in 15 adult patients with DS (M/F: 8/7; age 26.5 +/- 2.2 years;
      body mass index, BMI: 25.7 +/- 1.0 kg/m2) in which the potentiating effect of PD
      on GH secretion has been reported to be reduced. The results in DS were compared
      to those in 15 normal subjects (NS) (M/F: 8/7; age: 30.0 +/- 1.3 years; BMI: 21.4
      +/- 0.4 kg/m2). Basal GH and insulin growth factor I (IGF-1) levels in DS (1.8 +/
      0.7 and 206.5 +/- 21.0 micrograms/l) were similar to those in NS (1.4 +/- 0.3
      and 179.4 +/- 11.0 micrograms/l). The GH response to GHRH alone in DS (526.5 +/-
      120.1 micrograms/l/h) was lower (p < 0.05) than that recorded in NS (895.4 +/-
      153.7 micrograms/l/h). The GHRH-induced GH rise was potentiated by PD both in DS
      (1,138 +/- 184.2 micrograms/l/h; p < 0.02 vs. GHRH alone) and in NS (2,213.8 +/-
      212.8 micrograms/l/h; p < 0.005 vs. GHRH alone); however, as the percent
      potentiating effect of PD was similar in both groups (215 and 247%, respectively)
      the GH response to GHRH + PD in DS was lower (p < 0.005) than that in NS. The
      GHRH-induced GH rise was also potentiated by ARG in both DS (2,243 +/- 362.4
      micrograms/h; p < 0.001 vs. GHRH alone) and NS (2,764.3 +/- 325.7 micrograms/l/h;
      p < 0.005 vs. GHRH alone). As the percent potentiating effect of ARG in DS was
      more marked than in NS (425 vs. 308%, respectively), the GH response to GHRH +
      ARG became similar in both groups. No sex-related difference was found in the GH
      response to various stimuli both in DS and NS. In conclusion, these data
      demonstrate that the potentiating effect of PD but not that of ARG is impaired in
      adults with DS in whom a reduced somatotrope responsiveness to GHRH is present.
      These findings indicate that in DS the pituitary GH releasable pool is fully
      preserved while an impairment of the tuberoinfundibular cholinergic pathways
      could lead to somatostatinergic hyperactivity and low somatotrope responsiveness
      to GHRH.

PMID- 9524799
TI  - Selective expression of Ser 199/202 phosphorylated tau in a case of
      frontotemporal dementia.
AB  - We examined a 65-year-old patient with clinicopathological features that met the
      criteria of frontotemporal dementia (FTD), particularly frontal lobe degeneration
      (FLD). He came from a family with concentrated occurrence of dementia symptoms in
      the presenium. Neuropathological examination disclosed brain atrophy locally
      pronounced on the frontotemporal lobes with characteristic neuronal loss,
      microvacuolation and astrocytic gliosis. There were no pathological hallmarks
      such as senile plaques, Pick bodies (PBs), achromatic cells and neurofibrillary
      tangles. Precise separation of FTD from Pick disease (PD) and motor neuron
      disease with dementia (MNDD) has not yet been established, and they are included
      in one spectrum. Antibodies against paired helical filament tau protein
      demonstrated immunopositive cytoskeletal structures within the neurons as well as
      the glial cells in the brain of the present case. They were selectively stained
      with tau 199/202 but not tau 396, which were provided newly to recognize
      phosphorylation at Ser 199/202 or Ser 396 in tau, respectively. We investigated
      tau pathology in the present case in comparison to 8 cases with PD that were
      clinicopathologically confirmed. Neither tau 199/202 nor tau 396 stained the CNS
      structures in PD cases with few PBs, while both stained evidently those as well
      as PBs in PD cases associated with many PBs; so that the present case could be
      distinguished from PD on the basis of the immunoreactivity to site-specific
      phosphorylated tau. Our result suggests that FTD, especially familial FLD type
      might involve unique tau pathology, no matter whether FLD is a distinct entity
      from PD, or a variant form in the wide FTD spectrum including PD and MNDD and
      other related disorders.

PMID- 9524800
TI  - Inferior temporal lobe atrophy and APOE genotypes in Alzheimer's disease. X-ray
      computed tomography, magnetic resonance imaging and Xe-133 SPECT studies.
AB  - The apolipoprotein E (APOE) gene epsilon 4 allele is known to be associated with
      late-onset familial and sporadic Alzheimer's disease (AD). We assessed the
      possible relationship between APOE genotypes and morphological or functional
      changes in AD brains by x-ray computed tomography (CT), magnetic resonance
      imaging (MRI) and Xe-133 single photon emission CT (SPECT). First, we estimated
      the change in size of the whole brain and total ventricular system by using two x
      ray CT indices, the cerebral index (CI) and ventricular index (VI), respectively.
      Neither CI nor VI differed significantly among APOE genotypes. Then, we focused
      on the inferior temporal lobe regions by introducing new MRI indices, the
      inferior temporal index (ITI), temporal horn index (THI) and infero-medial
      temporal index (IMTI). We found a significant difference in each MRI index among
      APOE subgroups; ITI and IMTI were lower, while THI was higher in AD patients with
      at least one APOE epsilon 4 allele (epsilon 4+ group) than in those without such
      an allele (epsilon 4-group). Finally, we compared relative regional cerebral
      blood flow (rCBF) of Xe-133 SPECT among the AD subgroups. Relative rCBF in the
      cerebral cortex, particularly in the temporal lobe, was lower in the epsilon 4+
      group than in the epsilon 4- group. These results indicate that possession, and
      thus expression, of the APOE epsilon 4 allele affects preferentially the inferior
      temporal lobe, encompassing the hippocampus and amygdala, in AD patients.

PMID- 9524801
TI  - Explicit memory in frontotemporal dementia: the role of medial temporal atrophy.
AB  - In our memory clinic experience, memory impairment differs widely in patients
      with frontotemporal dementia (FTD). We searched for a correlation between
      explicit memory disturbance assessed with the Grober and Buschke test and medial
      temporal atrophy on CT scan in 22 consecutive patients with FTD. Five of the 22
      patients had a medial temporal lobe (MTL) atrophy. There was no significant
      difference between the two groups for the demographic characteristics. Free
      recall, cued recall and the learning curve were significantly better in patients
      without MTL atrophy. The patients with MTL atrophy made more intrusions. We found
      a positive correlation between total recall and cued recall and the mean of
      medial temporal lobe measurement. These results are in agreement with the role of
      the hippocampal formation in the memory process. In our group, the ratio of
      patients with MTL atrophy is similar to the ratio of Pick's disease in
      frontotemporal dementia. In histological series more severe hippocampal atrophy
      are reported in Pick's disease. Therefore MTL atrophy on CT scan could be a
      marker of Pick's disease in FTD.

PMID- 9524802
TI  - Possible roles of transglutaminases in Alzheimer's disease.
AB  - The localizations of two transglutaminases [factor XIIIa and tissue
      transglutaminase (tTG)] and their mRNAs were examined in human brain tissues from
      neurologically normal and Alzheimer disease (AD) cases, using immunohistochemical
      and in situ hybridization methods. In all cases, meningeal macrophages and
      ependymal macrophage/microglia were positive for factor XIIIa. The mRNA encoding
      factor XIIIa was detected in macrophages and microglia. As reported previously,
      intense staining with the antibody to factor XIIIa of a subset of microglia was
      seen in the parietal cortex in AD brains. Few or no microglia were found
      associated with classical senile plaques. In contrast, many labeled microglia
      were associated with primitive plaques. Further-more, most of these cells were
      mainly seen in the subpial cortical layer but were very rare in the hippocampus.
      On the other hand, few factor-XIIIa-positive microglia were found in the parietal
      cortices from non-neurological cases, but moderate numbers were found in their
      hippocampal tissues. TG and its mRNA were localized in astrocytes in all the
      cases. In AD, a few neurofibrillary tangles were positive to tTG. These results
      suggest that the subsets of microglia which express factor XIIIa may play some
      roles in the early phase of AD pathology.

PMID- 9524803
TI  - Factors affecting the utilization of homecare supports by caregiving relatives of
      Alzheimer patients.
AB  - Thirty-six homecare patients with dementia of Alzheimer type (DAT) and their
      caregiving relatives were studied to determine the factors influencing their use
      or nonuse of available medical, institutional, instrumental, and legal supports.
      The rate of utilization of homecare support was found to be surprisingly low.
      Only when the burden of providing care had become intolerable did relatives
      resort to homecare support (homecare allowance, counseling, outpatient services,
      etc.). The main reason for the low utilization was poor knowledge regarding the
      availability of homecare supports. Since all of the DAT patients were under the
      care of a family doctor, this information deficit could best be overcome by
      improved counseling from personal physicians.

PMID- 9524804
TI  - Predictive properties of referral communications for mental illness and dementia
      in a community.
AB  - As a measure of community awareness, this study examined the predictive
      properties of the diagnoses in referral communications for mental illness and
      dementia in elderly people. The patients were referred to the Aged Care
      Assessment Team from diversified sources over an 18-month period, the referral
      initiators being the general practitioner (GP), community nurse, family and
      others. There were 90 patients with dementia and 32 with psychiatric disorders.
      The referral letters were examined retrospectively as to the content and yield
      identifying a definite or possible diagnosis of dementia or psychiatric illness.
      The GP and community nurse had comparable rates of success as compared with the
      other two groups. The ability of the GP and other groups to diagnose functional
      psychiatric disorders was generally negative.

PMID- 9524805
TI  - Molecular mechanisms of developmental disorders.
AB  - One of the central tenets of developmental psychopathology is the belief that we
      can learn more about normal functioning through the study of psychopathology and
      arrive at a better understanding of pathological conditions through
      investigations of normal behavior. Advances in knowledge from one area will
      inform us regarding mechanisms at work in the other. A similar perspective is the
      driving force behind recent scientific advances in our understanding of certain
      developmental disorders. In this paper, molecular findings for four developmental
      disorders are reviewed: Prader-Willi syndrome, fragile X syndrome, Williams
      syndrome, and lissencephaly. These disorders were chosen for discussion because
      putative genes for each of them have been isolated. The ways in which mutations
      within these genes disrupt normal cognitive and behavioral functioning are
      discussed. Although considerable progress has been achieved in understanding the
      genetic mechanisms for these illnesses, much more research is needed to identify
      the environmental and genetic factors that interact to contribute to the
      expression of the more complex behavioral disorders.

PMID- 9524806
TI  - Earned security, daily stress, and parenting: a comparison of five alternative
      models.
AB  - Research suggests that adults who have developed a coherent perspective on their
      negative, early attachment relationships (i.e., earned secures) do not reenact
      poor parenting practices with their own children. However, no studies have
      addressed whether earned secures maintain positive parenting under the pressures
      of aversive environmental conditions. This study tested five alternative models
      that predict how earned secures parent under low and high stress in comparison to
      adults who had a positive upbringing (i.e., continuous secures) and adults who
      have an incoherent perspective on a troubled childhood (i.e., insecures). Only if
      earned secures exhibit effective caregiving under high stress, in comparison to
      the other security groups, can it be assumed that they have broken the
      intergenerational cycle of poor parenting. The Adult Attachment Interview was
      used to classify 97 mothers as earned secure, continuous secure, and insecure.
      Home observations of parenting and maternal self-reports of daily hassles (our
      stress measure) were obtained when children were 27 months old. Planned
      comparisons revealed that the diathesis-stress/incoherent present state of mind
      model most accurately predicted parenting. Thus, under high stress, the earned
      secures parented equivalently to the continuous secures and more positively than
      the insecures; under low stress no group differences were obtained. These
      findings indicate that in a normative sample earned secures break the
      intergenerational cycle and exhibit resilient parenting even under high stress
      conditions.

PMID- 9524807
TI  - Coparental and family group-level dynamics during infancy: early family
      precursors of child and family functioning during preschool.
AB  - This study examines longitudinal correlates of coparental and family group-level
      dynamics during infancy. Thirty-seven couples observed at play with their 8-11
      month-old infants (15 boys, 22 girls) rated their child's internalizing and
      externalizing symptoms, and their own coparenting behavior 3 years later.
      Teachers also rated child behavior at the 3-year follow-up. Several significant
      relationships emerged between observed family process (high hostility
      competitiveness, low family harmony, and high parenting discrepancies in the
      triad) at Time 1, and subsequent reports of child and coparenting behavior at
      Time 2. Larger parenting discrepancies at Time 1 predicted greater child anxiety
      as rated by teachers; greater hostility-competitiveness and lower harmony
      forecast higher child aggression. Time 1 family process continued to predict Time
      2 aggression even after controlling for individual and marital functioning.
      Several links were also found between distressed family process and later
      parental reports of negative coparenting behavior. These parental reports of
      coparenting also explained unique variance in concurrent child behavior ratings.
      The significance of coparenting as a distinct family construct is discussed.

PMID- 9524808
TI  - Factors associated with abusive relationships among maltreated and nonmaltreated
      youth.
AB  - This study sought to understand how experiences of maltreatment occurring prior
      to 12 years of age affect adolescent peer and dating relationships. A school
      based sample of 15-year-olds was divided into maltreated (n = 132) and
      nonmaltreated (n = 227) subgroups based on self-reported maltreatment. These two
      groups were then compared on two theoretically determined dimensions of
      adjustment (i.e., interpersonal sensitivity/hostility; personal resourceS) and
      self- and teacher-report measures of peer and dating relationships. Findings
      supported the hypothesis that maltreated youths significantly differed from
      nonmaltreated youths in terms of adjustment problems as well as conflict with
      dating partners and close friends. Maltreated youths reported significantly more
      verbal and physical abuse both toward and by their dating partners, and were seen
      by teachers as engaging in more acts of aggression and harassment toward others.
      In regression analyses, the significant association between maltreatment and
      dating conflict for males was strengthened by including adjustment dimensions in
      the equation; for females, adjustment variables mediated the association between
      maltreatment and dating conflict. Results are discussed in relation to a
      maladaptive interpersonal trajectory for maltreated children, wherein a violent
      interactional dynamic in adolescent close relationships may be setting the stage
      for violence in intimate partnerships.

PMID- 9524809
TI  - Peer group victimization as a predictor of children's behavior problems at home
      and in school.
AB  - This study reports a short-term prospective investigation of the role of peer
      group victimization in the development of children's behavior problems, at home
      and in school. Sociometric interviews were utilized to assess aggression,
      victimization by peers, and peer rejection, for 330 children who were in either
      the third or fourth grade (approximate mean ages of 8-9 years old). Behavior
      problems were assessed using standardized behavior checklists completed by
      mothers and teachers. A follow-up assessment of behavior problems was completed 2
      years later, when the children were in either the fifth or sixth grade
      (approximate mean ages of 10-11 years old). Victimization was both concurrently
      and prospectively associated with externalizing, attention dysregulation, and
      immature/dependent behavior. Victimization also predicted increases in these
      difficulties over time, and incremented the prediction in later behavior problems
      associated with peer rejection and aggression. The results of this investigation
      demonstrate that victimization in the peer group is an important predictor of
      later behavioral maladjustment.

PMID- 9524810
TI  - The role of exposure to community violence and developmental problems among inner
      city youth.
AB  - While research has well documented that urban youth are exposed to increasing
      rates of community violence, little is known about what increases risk for
      violence exposure, what protects children from exposure to violence, and what
      factors reduce the most negative outcomes associated with witnessing violence.
      This study expands on current research by evaluating the relations between
      exposure to violence, family relationship characteristics and parenting
      practices, and aggression and depression symptoms. Data were drawn from a sample
      of 245 African-American and Latino boys and their caregivers from economically
      disadvantaged inner-city neighborhoods in Chicago. Rates of exposure could not be
      predicted from family relationship and parenting characteristics, although there
      was a trend for discipline to be related. Exposure to community violence was
      related to increases in aggressive behavior and depression over a 1-year period
      even after controlling for previous status. Future studies should continue to
      evaluate the role of exposure to violence on the development of youth among
      different neighborhoods and communities. Implications for intervention and policy
      are discussed.

PMID- 9524812
TI  - A 120 kilobase resolution contig map of the rice genome.
AB  - 92% of the rice genome (4.3 x 10(8) bp, 2n = 24) was covered by 631 contigs of
      various length, which were generated by fingerprinting from a representative and
      genetically stable bacterial artificial chromosome (BAC) library of the Guang Lu
      Ai 4 (a O. Sativa variety) genome with the average insert of 120 kb in length. To
      form the contig map, 565 molecular markers of RFLP, STS, cDNA and anchor set
      derived from two O. Sativa varieties were by colony hybridization mapped to the
      contigs, which were then assigned to and ordered along the particular chromosomes
      according to the marker colinearity. Being highly conserved DNA sequences shared
      among the genomes of rice, barley, wheat, oat, maize, sorghum and sugar cane, 89
      anchor markers mapped help to identify the rice genes through the information
      provided by the maps of relative genomes, and vice versa. Numerous repeated DNA
      sequences of various length were identified and mapped to the chromosomes.
      Physical distances have been determined for hundreds pairs of adjacent markers,
      which would facilitate the identification by map-based cloning the rice genes of
      interest. The accuracy of clone overlaps in contigs was further confirmed by the
      existence in contigs of well fit stacks of marker-lodged clones independently
      identified by hybridization. Large scale DNA sequencing of individual chromosomes
      could now be initiated simply by selecting and sequencing the minimally
      overlapped BAC clones of the contigs.

PMID- 9524813
TI  - The isolation, localization and characterization of the QM homolog in Drosophila
      melanogaster.
AB  - A fragment of 443 bp was amplified from a lambda ZAPII Drosophila central nervous
      system (CNS) cDNA library using minimally degenerate primers to very conserved
      regions of the QM gene. This fragment was used as a probe to screen the lambda
      ZAPII Drosophila CNS cDNA library. Two clones of the Drosophila QM homolog (pDQM
      7A1 and pDQM-2B1), each containing the complete coding region, were isolated. The
      5'-UTR of this gene was obtained by RACE PCR and ligated to the coding sequence
      to produce a the full-length copy of the Drosophila QM homolog (DQM) cDNA. The
      DQM cDNA measures 746 nucleotides in length and encodes a polypeptide of 218
      residues. The amino acid sequence shows 76.1 percent identity with human QM and
      69.1 percent identity with QSR1, the yeast homolog of QM. Unlike the human or
      mouse genome which contains multiple copies of the QM gene, the Drosophila genome
      has only a single copy as indicated by genomic Southern blot analysis. In situ
      hybridization confirms the presence of a single copy of DQM in the Drosophila
      genome and localizes it to the left arm of the third chromosome at the end of
      region 80A (80A-4).

PMID- 9524811
TI  - Multiple jeopardy: risk and protective factors among addicted mothers' offspring.
AB  - Objectives of this study were to ascertain risk and protective factors in the
      adjustment of 78 school-age and teenage offspring of opioid- and cocaine-abusing
      mothers. Using a multimethod, multiinformant approach, child outcomes were
      operationalized via lifetime psychiatric diagnoses and everyday social competence
      (each based on both mother and child reports), and dimensional assessments of
      symptoms (mother report). Risk/protective factors examined included the child
      sociodemographic attributes of gender, age, and ethnicity, aspects of maternal
      psychopathology, and both mother's and children's cognitive functioning. Results
      revealed that greater child maladjustment was linked with increasing age,
      Caucasian (as opposed to African American) ethnicity, severity of maternal
      psychiatric disturbance, higher maternal cognitive abilities (among African
      Americans) and lower child cognitive abilities (among Caucasians). Limitations of
      the study are discussed, as are implications of findings for future research.

PMID- 9524814
TI  - Nucleotide sequence of nucleocapsid protein (N) of Hantaan virus isolated from a
      Korean hemorrhagic fever patient.
AB  - The nucleotide sequence of the nucleocapsid protein (N) coding region of a
      Hantaan virus strain (CFC94-2) isolated from a Korean Hemorrhagic Fever (KHF)
      patient was determined by sequencing a series of deletion mutants. Comparison of
      the N coding sequence of CFC94-2 to the sequence of the prototype of Hantaan
      virus, strain 76-118 reveals a 4.97% difference in the nucleotide sequence and a
      1.6% difference in the deduced amino acid sequence. The rate of amino acid
      sequence variation in N protein of different Hantaan viruses (1.6%) is quite
      similar to that in G1 and G2 envelope proteins (1.7%). These results suggest that
      N protein may be under a similar selection pressure to G1 and G2 envelope
      proteins against host immune system.

PMID- 9524816
TI  - Genomic sequence and mapping of a methyljasmonate-induced O-methyltransferase
      from barley (Hordeum vulgare L.).
AB  - We have isolated a genomic clone corresponding to a caffeic acid O
      methyltransferase (COMT) from barley (Hordeum vulgare L.) using a cDNA for a
      previously described jasmonate-regulated mRNA showing homology to COMT. Primer
      extension was used to characterize the 5' end of the mRNA while the 3' end,
      intron/exon structure and other features of the sequence were deduced by
      comparison to the cDNA sequence and/or conserved motifs. The gene is mapped to
      chromosome five and is absent in the barley cultivar Morex. Southern and northern
      analyses suggest that no differences in genomic structure and jasmonate
      inducibility exist between the barley cultivar Salome (source of the cDNA clone)
      and Igri (source of the genomic clone). This genomic clone is thus suitable for
      promoter studies with respect to jasmonate induction.

PMID- 9524815
TI  - Nucleotide and deduced amino acid sequences of Biomphalaria glabrata actin cDNA.
AB  - The complete nucleotide sequence of Biomphalaria glabrata actin has been cloned
      by PCR amplification and screening of a cDNA library of Biomphalaria glabrata.
      The comparison of the deduced amino acid sequence with other actins suggests that
      a cytoskeletal form of the protein has been cloned.

PMID- 9524817
TI  - Nucleotide sequence of canine herpesvirus homologues of herpes simplex virus type
      1 US2, US3, glycoproteins I and E, US8.5 and US9 genes.
AB  - The partial nucleotide sequence of two BamHI fragments that span the unique short
      region (US), terminal repeat region (TR) and internal repeat region (IR) of
      canine herpesvirus (CHV) has been determined. Data obtained revealed several open
      reading frames (ORF's) identified as the US2, US3, gI, gE and US9 homologues of
      herpes simplex virus type 1 (HSV1). The CHV homologues also show significant
      identity in amino acid sequence with those encoded by feline herpesvirus type 1
      (FHV1), bovine herpesvirus (BHV1) and equine herpesvirus (EHV1). Translation of
      another ORF showed little amino acid identity with the gene products of other
      alpha-herpesviruses. Its genomic position relative to the other CHV homologues
      would suggest it is the US8.5 gene of CHV.

PMID- 9524818
TI  - Cloning and deduced amino acid sequence of human nicotinamide nucleotide
      transhydrogenase.
AB  - Pyridine nucleotide transhydrogenases (E.C.1.6.1.1) are integral proteins of the
      inner mitochondrial membrane. These enzymes are part of the energy-transfer
      system of the respiratory chain and specifically catalyze the transfer of a
      hydride ion between nicotinamide adenine dinucleotide, NAD(H), and oxidized
      nicotinamide dinucleotide phosphate, NADP(H). Here we report the sequence of full
      length cDNA clone containing the coding sequence for human mitochondrial
      nicotinamide nucleotide transhydrogenase. The characterized cDNA contains an
      insert of 4,232 base pairs with a 91% sequence identity to a previously
      characterized bovine transhydrogenase cDNA. The deduced human polypeptide
      sequence displays a high degree of sequence similarity, 97%, to the bovine
      polypeptide and a comparison of the two sequences is presented.

PMID- 9524819
TI  - Cloning and sequencing of equine transforming growth factor-beta 1 (TGF beta-1)
      cDNA.
AB  - Transforming growth factor beta (TGF-beta) belongs to a family of peptide growth
      factors which control critical stages of cell proliferation and differentiation.
      We report the cloning and sequencing of the cDNA for TGF-beta type 1 isoform of
      the horse. The predicted mature equine TGF beta-1 peptide is 112 amino acids in
      length and exhibits 99% identity to mature human TGF beta-1.

PMID- 9524820
TI  - Identification and characterization of an MGSA/GRO pseudogene.
AB  - Three linked genes for the CXC-chemokine melanoma growth stimulatory
      activity/growth related protein (MGSA/GRO) have been previously characterized and
      mapped to chromosome 4q12-q13. We have isolated and characterized a pseudogene,
      MGSA/GRO delta, which is 83% similar to the MGSA/GRO alpha gene in the region
      spanning the 5' UTR, first and second exons, and the first intron. The 5'
      upstream sequence for the MGSA/GRO delta gene, which is also very similar to the
      MGSA/GRO alpha, beta, gamma genes, contains a conserved NF-kappa B motif, a TATA
      box, and a transcription initiation site. However, the sequence becomes markedly
      divergent after the second exon and hybridization studies indicate that sequences
      similar to the third and forth exons of other MGSA/GRO genes are not present in
      this gene. Additional sequence differences include alteration of the MGSA/GRO
      delta translation initiation codon and a one base insertion resulting in an
      apparent frame shift and early termination within exon 2. Multiple mutations such
      as these are characteristic of pseudogenes.

PMID- 9524821
TI  - Herpes simplex viruses.

PMID- 9524822
TI  - Refractory mucosal candidiasis in patients with human immunodeficiency virus
      infection.
AB  - Difficult-to-manage mucosal candidal infection has been a hallmark of individuals
      with advanced infection due to human immunodeficiency virus type 1. In this AIDS
      Commentary, Drs. Fichtenbaum and Powderly comprehensively review the literature
      and their experience with refractory candidiasis in such patients. Of interest is
      their delineation of resistance, a lack of susceptibility to an antifungal agent
      in vitro among patients with refractory or clinically unresponsive disease. These
      authors believe that the establishment of resistance should be based upon
      standards established by the National Committee on Clinical Laboratory Standards,
      which they propose to define as a failure to respond to systematic therapy with
      specific doses of itraconazole, fluconazole, or parenterally or orally
      administered amphotericin B within 14 days. There have been many definitions of
      "refractory candidiasis," and the one proposed by these authors will be debated;
      however, this definition has the advantage of establishing a standard by which to
      judge the efficacy of their proposed algorithm for the treatment of persistent or
      refractory oropharyngeal candidal infections. Drs. Fichtenbaum and Powderly have
      performed a useful service in their attempt to bring coherence to the management
      of this common and often vexing problem.

PMID- 9524824
TI  - Occupational infection with hepatitis B virus--waging war against an insidious,
      intractable, intolerable foe.

PMID- 9524823
TI  - Prediction of response to hepatitis B vaccine in health care workers: whose
      titers of antibody to hepatitis B surface antigen should be determined after a
      three-dose series, and what are the implications in terms of cost-effectiveness?
AB  - We identified the demographics of 385 health care workers (HCWs) to identify
      those whose chance of developing a protective response to a standard primary
      hepatitis B immunization series was so high that the need for testing for
      antibodies to hepatitis B surface antigen (anti-HBs) would be obviated following
      immunization. In addition, using sensitivity analysis, we analyzed the economic
      consequences of not determining anti-HBs titers for any individual after primary
      immunization and of using the Centers for Disease Control and Prevention (CDC)
      recommended post-hepatitis B exposure prophylaxis for high-risk HCWs. Nonsmoking
      women < 50 years old with a weight-height index of < 42 had a 98.2 +/- 0.9%
      chance of developing a protective anti-HBs titer. Male nonsmokers < 50 years old
      with a weight-height index of < 29 had a 94.7 +/- 1.8% chance of a protective
      response. Economic analysis revealed that use of the CDC guidelines for post
      hepatitis B exposure prophylaxis in male HCWs whose anti-HBs status is unknown is
      always more cost-effective than determining anti-HBs titers following primary
      immunization for those at high risk. In female HCWs, post-hepatitis B exposure
      prophylaxis is more cost-effective until hepatitis B exposure rats are
      approximately 50%. It is possible to predict who will have a high probability of
      developing a protective response to hepatitis B vaccine; for these people,
      determining postimmunization anti-HBs titers is unnecessary and not cost
      effective.

PMID- 9524825
TI  - Photo quiz. Protothecosis.

PMID- 9524826
TI  - Randomized comparison of sulbactam/cefoperazone with imipenem as empirical
      monotherapy for febrile granulocytopenic patients.
AB  - In a prospective, randomized, controlled trial, we compared
      sulbactam/cefoperazone with imipenem as empirical monotherapy for febrile,
      granulocytopenic patients; 101 patients received sulbactam/cefoperazone (2 g/4 g
      every 12 hours) and 102 patients received imipenem (500 mg every 6 hours).
      Documented infections were present in 40% of patients treated with
      sulbactam/cefoperazone (40 of 101) and in 39% of patients receiving imipenem (40
      of 102). The number of pretherapy gram-positive pathogens (52 isolates) was twice
      the number of pretherapy gram-negative pathogens (26 isolates). The overall
      favorable clinical response rates for sulbactam/cefoperazone (91 of 103 patients,
      or 88%) and imipenem (84 of 104 patients, or 81%) were similar. Both drugs were
      generally well tolerated. However, diarrhea occurred more often in patients
      treated with sulbactam/cefoperazone (31 of 101 patients, or 31%, vs. 15 of 102
      patients, or 15%; P = .007), while seizures developed only in patients receiving
      imipenem (0 of 101 patients vs. 3 of 102 patients, or 3%). Superinfections
      developed in 16% of patients in both study groups but were infrequently caused by
      beta-lactam-resistant gram-negative bacilli (two cases with
      sulbactam/cefoperazone therapy and six cases with imipenem). These results
      support the efficacy and safety of either sulbactam/cefoperazone or imipenem as
      empirical monotherapy for febrile granulocytopenic patients.

PMID- 9524827
TI  - Invasive group A streptococcal disease in Taiwan is not associated with the
      presence of streptococcal pyrogenic exotoxin genes.
AB  - We reviewed the clinical features of 44 patients with invasive group A
      streptococcal (GAS) disease who were treated at two teaching hospitals in
      southern Taiwan from 1991 to 1994. Genes encoding streptococcal pyrogenic
      exotoxin types A (speA), B (speB), C (speC), and F (speF) and serotypes of M1,
      M6, and M12 were determined by polymerase chain reaction to target specific
      sequences in the 44 isolates recovered from these patients and in 28 isolates
      recovered from upper respiratory sites in 28 additional patients during the study
      period. The protease activity of these isolates was tested by using the casein
      plate method. Of the 44 patients with invasive diseases, 25 (57%) had no obvious
      underlying diseases, and 14 (32%) had preexisting neoplastic diseases or had
      previously used steroids. Twenty-five patients (57%) presented with cellulitis or
      necrotizing fasciitis, 24 (55%) had bacteremia, and eight (18%) had streptococcal
      toxic shock syndrome (STSS). Eight patients (18%) died of invasive GAS disease;
      seven had STSS, and seven had underlying diseases. All eight patients died within
      48 hours after hospitalization. The presence of speA, speC, or speF was not
      implicated in any particular clinical syndrome in patients with invasive GAS
      disease. High-level protease activity and the M1 serotype of the isolates were
      significantly associated with the clinical signs of STSS and with mortality. M1
      serotype and protease activity, as well as host immune status, might play
      significant roles in the pathogenesis of invasive GAS disease in Taiwan.

PMID- 9524828
TI  - Invasive pneumococcal disease in Dallas County, Texas: results from population
      based surveillance in 1995.
AB  - We studied the epidemiology of invasive disease caused by Streptococcus
      pneumoniae in 1995 among 1.9 million residents of Dallas County, Texas. The
      sociodemographic characteristics and chronic medical conditions of 432 patients
      were identified through active, population-based surveillance and review of
      medical records. The incidence of disease was 22 cases per 100,000 person-years
      and was highest for children < 2 years of age (136 cases per 100,000 person
      years) and for adults > or = 65 years of age (80 cases per 100,000 person-years).
      Twenty percent of isolates were nonsusceptible to penicillin; the highest rates
      of resistance were among the youngest and oldest age groups (28% and 22% of
      isolates, respectively). An increased incidence of disease was associated with
      low income (42 cases per 100,000 person-years) and black race (39 cases per
      100,000 person-years). The frequency of most chronic medical conditions increased
      with age; smoking, heavy alcohol use, and infection due to human immunodeficiency
      virus were most common between 30 and 64 years of age. Of otherwise healthy
      patients 30-64 years of age, 47% were current smokers, an association requiring
      further investigation. Characterizing groups at risk for invasive pneumococcal
      disease could aid in the development of prevention programs and increase the
      benefits from wide use of effective vaccines.

PMID- 9524829
TI  - Posttransplantation lymphoproliferative disorder associated with OKT3 and
      decreased antiviral prophylaxis in pancreas transplant recipients.
AB  - Between September 1994 and October 1995, we diagnosed and treated four cases of
      early onset posttransplantation lymphoproliferative disorder (PTLD) occurring
      within 62 days of pancreas transplantation. The development of PTLD was
      associated with both a significantly higher total muromonab-CD3 (OKT3) dose and a
      lack of ganciclovir/acyclovir prophylaxis, but it was not associated with the
      total dose of antithymocyte globulin or cytomegalovirus serostatus. All four
      patients were treated aggressively and survived without evidence of recurrent
      PTLD more than 1.5 years later. We conclude that the use of a high total dose of
      OKT3 puts pancreas transplant recipients at increased risk for early onset PTLD,
      while ganciclovir/acyclovir prophylaxis may help to prevent this disorder;
      however, if early onset PTLD does occur in these patients, aggressive therapy can
      lead to a favorable outcome.

PMID- 9524830
TI  - Successful medical management of isolated renal zygomycosis: case report and
      review.
AB  - We describe the medical management of isolated renal zygomycosis in an adult
      patient with AIDS during chemotherapy for AIDS-related lymphoma. After initial
      presentation during the first cycle of chemotherapy, the infection was contained
      within the kidney following recovery of the neutrophil count without medical or
      surgical intervention. Since he was not considered to be a candidate for
      nephrectomy, his infection was treated with amphotericin B lipid complex during
      subsequent chemotherapy. Neutropenia was minimized by the addition of cytokine
      support therapy with granulocyte colony-stimulating factor and reduced doses of
      chemotherapy. Following this strategy, his lymphoma completely resolved, and
      renal zygomycosis was controlled. At the time of this writing, he had been in
      complete remission for 18 months without evidence of progressive fungal
      infection. This report and our literature review indicate that isolated renal
      zygomycosis can be associated with a favorable prognosis, occurs with greatest
      frequency in patients with AIDS, is associated with parenteral access, and may be
      managed by medical therapy alone.

PMID- 9524831
TI  - Effect of cytomegalovirus infection on 1-year mortality rates among recipients of
      allogeneic bone marrow transplants.
AB  - The effect of cytomegalovirus (CMV) infection on 1-year mortality rates among
      allogeneic bone marrow transplant recipients who are receiving a standard
      protocol as prophylaxis for CMV infection is unclear. We determined the risk
      factors for death within 1 year among 103 bone marrow transplant recipients by
      performing a multivariate analysis. The results of donor and recipient CMV
      serologies did not predict 1-year mortality, although there was a trend towards
      higher mortality among CMV-seropositive recipients who received marrow from
      seronegative donors (P = .077). Multivariate analysis revealed that the factors
      independently associated with 1-year mortality were the development of CMV
      antigenemia (relative risk [RR] = 2.74; confidence interval [CI] = 1.28-5.86),
      bone marrow transplantation (BMT) from unrelated donors (RR = 3.20; CI = 1.30
      7.92), and severe acute graft-versus-host disease (RR = 3.50; CI = 1.50-8.17).
      Although significant on univariate analysis, advanced underlying disease before
      BMT and the development of active CMV disease after BMT were not independent risk
      factors. In conclusion, the development of CMV antigenemia after BMT was
      associated with increased 1-year mortality, while the development of active CMV
      disease was not. Reactivation of CMV infection may represent a marker of poor
      immune reconstitution or may contribute to further immunosuppression after BMT.

PMID- 9524833
TI  - Primary pulmonary botryomycosis: case report and review.
AB  - Botryomycosis is an uncommon bacterial disease characterized by the microscopic
      formation of eosinophilic granules that resemble those of infection by
      Actinomyces species. The diagnosis of botryomycosis can be made when microscopic
      inspection and culture of the granules reveal gram-positive cocci or gram
      negative bacilli. Botryomycosis is caused by common bacterial pathogens including
      Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa, yet the host
      and microbial factors that contribute to the pathobiology remain unknown.
      Pulmonary botryomycosis can resemble actinomycosis, tuberculosis, or invasive
      carcinoma by causing a mass lesion with constitutional symptoms.
      Radiographically, it invades bone and disrupts tissue planes. Successful
      treatment often requires a combination of both surgical debridement and long-term
      antimicrobial therapy. We report a case of primary pulmonary botryomycosis and
      review the literature on this unusual infectious process.

PMID- 9524832
TI  - Once weekly azithromycin therapy for prevention of Mycobacterium avium complex
      infection in patients with AIDS: a randomized, double-blind, placebo-controlled
      multicenter trial.
AB  - We conducted a randomized, double-blind, placebo-controlled multicenter trial of
      azithromycin (1,200 mg once weekly) for the prevention of Mycobacterium avium
      complex (MAC) infection in patients with AIDS and a CD4 cell count of < 100/mm3.
      In an intent-to-treat analysis through the end of therapy plus 30 days, nine
      (10.6%) of 85 azithromycin recipients and 22 (24.7%) of 89 placebo recipients
      developed MAC infection (hazard ratio, 0.34; P = .004). There was no difference
      in the ranges of minimal inhibitory concentrations of either clarithromycin or
      azithromycin for the five breakthrough (first) MAC isolates from the azithromycin
      group and the 18 breakthrough MAC isolates from the placebo group. Of the 76
      patients who died during the study, four (10.5%) of 38 azithromycin recipients
      and 12 (31.6%) of 38 placebo recipients had a MAC infection followed by death (P
      = .025). For deaths due to all causes, there was no difference in time to death
      or number of deaths between the two groups. Episodes of non-MAC bacterial
      infection per 100 patient years occurred in 43 azithromycin recipients and 88
      placebo recipients (relative risk, 0.49; 95% confidence interval, 0.33-0.73). The
      most common toxic effect noted during the study was gastrointestinal, reported by
      78.9% of azithromycin recipients and 27.5% of placebo recipients. Azithromycin
      given once weekly is safe and effective in preventing disseminated MAC infection,
      death due to MAC infection, and respiratory tract infections in patients with
      AIDS and CD4 cell counts of < 100/mm3.

PMID- 9524834
TI  - Clinical and microbiological assessment of Mycobacterium simiae isolates from a
      single laboratory in southern Arizona.
AB  - Mycobacterium simiae was the third most common mycobacterium identified over a 2
      year period from a single clinical laboratory in southern Arizona. Thirty-three
      isolates from 25 patients were identified over 1 year. The isolation of M. simiae
      was considered clinically significant for only two of 23 evaluable patients. None
      of five patients with human immunodeficiency virus infection had clinical disease
      associated with M. simiae. Twenty isolates were available for detailed study. All
      but one of the 20 isolates were niacin-negative, and 11 were nonphotochromogenic.
      All 20 isolates had a triple-cluster pattern consistent with M. simiae by high
      performance liquid chromatography, and restriction fragment patterns were
      identical for 16 isolates. Analysis of 16S rDNA confirmed the identity of all the
      tested isolates as M. simiae. In this study, M. simiae was a frequent clinical
      isolate but was rarely associated with disease. The organisms isolated were
      confirmed to be M. simiae but appeared to be phenotypically distinct strains of
      low virulence.

PMID- 9524835
TI  - Varying titers of neutralizing antibodies to streptococcal superantigens in
      different preparations of normal polyspecific immunoglobulin G: implications for
      therapeutic efficacy.
AB  - Inasmuch as normal intravenous polyspecific immunoglobulin G (IVIG) neutralizes
      the activity of a wide spectrum of superantigens, it may be an efficient
      adjunctive therapy for diseases associated with superantigen-producing organisms,
      including severe group A streptococcal diseases. The neutralizing activity
      against purified superantigens, streptococcal pyrogenic exotoxins (Spe), and a
      mixture of superantigens present in culture supernatant of clinical group A
      streptococcal isolates was determined for five IVIG preparations. A significant
      variation among different IVIG preparations (P < .05) and different lots of the
      same IVIG brand (P < .044) was found. Neutralization of SpeA activity was
      significantly lower than that of other streptococcal superantigens (P < .05);
      however, there was no correlation between SpeA binding and SpeA neutralizing
      activity in different IVIGs. Plasma samples obtained from patients after IVIG
      infusion varied in their titers of neutralizing antibodies to culture
      supernatants prepared from their respective isolates, and this variation
      paralleled differences in the neutralizing titer of the IVIG lot administered to
      each patient studied. The study suggests that complete neutralizing activity may
      be achieved by optimizing the type and/or dose of IVIG used in treatment.

PMID- 9524836
TI  - Rationale for the use of intravenous gamma globulin in the treatment of
      streptococcal toxic shock syndrome.

PMID- 9524837
TI  - Risk factors for candidemia in a children's hospital.
AB  - Candida species are increasingly important nosocomial pathogens in critically ill
      children. A 2.3-fold increase in the rate of nosocomial candidemia at our 200-bed
      tertiary care children's hospital prompted a study to identify risk factors for
      this infection. Twenty-six cases were identified between 1992 and 1993,
      representing 21% of all nosocomial bloodstream infections. Candida albicans was
      the most frequent isolate (58%), followed by Candida parapsilosis (27%). A case
      control study revealed that there was a statistically significant association
      between the occurrence of candidemia and placement of a central venous catheter
      in the femoral vein (P = .03), the use of a tunneled central venous catheter (P =
      .05), and prolonged hyperalimentation (P = .04). Patients with candidemia also
      were noted to have candiduria more often than controls (P = .003) and were more
      likely to have had topical antifungal agents prescribed (P = .04). Multivariate
      analysis showed that hyperalimentation was an independent risk factor for the
      development of candidemia. We conclude that measures must be taken to reduce
      these risk factors whenever possible.

PMID- 9524838
TI  - Use of the cytomegalovirus (CMV) antigenemia assay for the rapid diagnosis of
      primary CMV infection in hospitalized adults.
AB  - We assessed the value of the cytomegalovirus (CMV) antigenemia assay for
      diagnosing primary CMV infection in adults. The CMV antigenemia assay was
      performed for 40 patients admitted to our unit over a 2-year period with
      unexplained fever and suspected primary CMV infection. Nine of the 10 patients
      with primary CMV infection had positive CMV antigenemia assays, and the results
      were available within 5 hours. All 10 patients had a mononucleosis-like syndrome.
      All but one of the 30 other patients had negative CMV antigenemia assays. A false
      positive result was obtained for a patient with systemic lupus erythematosus.
      Overall, the CMV antigenemia assay was 90% sensitive and 96% specific for the
      diagnosis of primary CMV infection. Therefore, the CMV antigenemia assay appears
      to be a simple, rapid, inexpensive test for the diagnosis of primary CMV
      infection in hospitalized adults.

PMID- 9524839
TI  - Indwelling device-related and recurrent infections due to Aeromonas species.
AB  - From October 1995 to February 1997, 13 isolates of Aeromonas species were
      recovered from four patients treated at National Taiwan University Hospital
      (Taipei). One of the patients, a diabetic, had simultaneous Aeromonas veronii
      biotype veronii bacteremia and A. veronii biotype sobria urinary tract infection.
      Seven weeks after the episode, the patient had necrotizing fasciitis due to A.
      veronii biotype veronii. The other three patients all had underlying
      hepatobiliary malignancies complicated by obstructive jaundice, and all underwent
      percutaneous transhepatic cholangiographic drainage. These three patients had
      multiple isolates of Aeromonas species (A. hydrophila and/or A. caviae) recovered
      from samples of blood or bile or from catheter insertion sites. All isolates were
      identified on the basis of the results of extended biochemical tests as well as
      characteristic cellular fatty acid profiles. The results of genotyping generated
      by arbitrarily primed polymerase chain reaction and of susceptibility testing
      showed that these Aeromonas species were pathogens that caused indwelling device
      related infections and that the organisms could persist for long periods, with
      subsequent recurrence of severe infection. Concomitant infection due to more than
      one Aeromonas species or caused by polyclonal A. hydrophila or A. veronii biotype
      veronii was also documented.

PMID- 9524840
TI  - Perspectives on switching oral acyclovir from prescription to over-the-counter
      status: report of a consensus panel.
AB  - The proposed switching of oral acyclovir from prescription to over-the-counter
      (OTC) status for the 5-day episodic treatment of genital herpes was considered by
      a consensus panel. It was concluded that self-diagnosis/misdiagnosis, misuse, and
      adverse drug effects were potential problems with the OTC use of acyclovir. While
      acyclovir reduces asymptomatic shedding of herpes simplex virus type 2, the
      reduction in transmission of virus potentially resulting from increased acyclovir
      use was felt to be of unknown extent but likely to be of benefit overall. The
      availability of acyclovir would likely be improved. There were differences in
      opinion as to whether widespread availability of acyclovir (prescription or OTC)
      may speed the development of viral resistance. However, all panel members felt
      that granting OTC status may set an undesirable precedent for the switch from
      prescription to OTC use of other systemically administered antiinfective agents.
      The effect of this precedent, in terms of accelerating development of multidrug
      resistant bacteria, was a major concern of all panel members. The consensus was
      that the switch of acyclovir to OTC status could not be supported.

PMID- 9524841
TI  - Reliability of procalcitonin concentrations for the diagnosis of sepsis in
      critically ill neonates.
AB  - We evaluated the reliability of serum concentrations of procalcitonin for the
      diagnosis of early- and late-onset sepsis in a neonatal intensive care unit
      (NICU) setting. Timed procalcitonin determinations were prospectively obtained
      during two postnatal periods: 0-48 hours of age (period 1) and 3-30 days of age
      (period 2). In period 1, we measured procalcitonin concentrations in 83 healthy
      newborns (group 0) and in 120 NICU patients (14 with culture-proven sepsis, group
      1A; 14 with clinical septicemia, group 1B; 75 with no evidence of infection,
      group 2; and 17 with uncertain findings, group 3). After we established 95% hour
      specific reference ranges for group 0, we performed multiple linear regression
      analyses to determine which maternal, intrapartum, and neonatal complications
      would affect normal procalcitonin values. Maternal diabetes was the only variable
      identified in group 2 patients that induced a significant deviation from
      procalcitonin reference ranges. Analyses of the pooled procalcitonin values
      obtained for group 1 patients over the 48-hour period after birth yielded a
      sensitivity of 92.6% and a specificity of 97.5% for procalcitonin concentrations
      in the detection of early-onset sepsis. In period 2, blood samples from 23 cases
      with systemic infections were analyzed for procalcitonin concentrations at the
      onset of signs of infection. The control group was formed by matching four
      uninfected NICU patients to each infected case. None of the procalcitonin values
      for the 92 controls overlapped those for the cases (sensitivity and specificity,
      100%). Procalcitonin is a promising marker for the diagnosis of early- and late
      onset sepsis in neonates at high risk for this infection.

PMID- 9524842
TI  - Detection of Enterocytozoon bieneusi in fecal specimens by polymerase chain
      reaction analysis with primers to the small-subunit rRNA.
AB  - Microsporidia are the suspected etiology of diarrhea in up to 30% of
      immunocompromised patients with AIDS. Epidemiological investigation of these
      organisms has been hampered by the lack of easy methods of detection. Currently,
      definitive identification requires small bowel biopsy and transmission electron
      microscopy (TEM) to confirm the species of microsporidia involved. We describe a
      method for the detection of microsporidia in stool specimens that utilizes
      polymerase chain reaction (PCR) analysis with use of primers V1 and EB450 based
      on the small-subunit rRNA gene of Enterocytozoon bieneusi. A guanidium
      thiocyanate (GuSCN) method was utilized to extract microsporidian DNA from feces.
      Consistent amplification was detected in stool samples from three patients with
      TEM-confirmed microsporidiosis due to E. bieneusi by means of these techniques.
      Optimization of this PCR reaction revealed that the sensitivity of the reaction
      was increased by the addition of dimethyl sulfoxide. This PCR method allows for
      detection of E. bieneusi in stool specimens and will be applied to
      epidemiological investigations of this organism in the future.

PMID- 9524843
TI  - Nosocomial infections caused by Sphingomonas paucimobilis: clinical features and
      microbiological characteristics.
AB  - From January 1995 to September 1996, 14 isolates of Sphingomonas paucimobilis,
      including 11 from clinical specimens from six patients with nosocomial infection
      and three from environmental sources, were collected. Two of the six patients had
      intravascular catheter-related bacteremia and one each had bacteremic biliary
      tract infection, urinary tract infection, ventilator-associated pneumonia, and
      wound infection. The S. paucimobilis isolates were identified according to
      biochemical profiles established with use of the API 20NE system and Vitek GNI
      card and the characteristic cellular fatty acid chromatogram. Ten biotypes, 11
      antibiograms (by the Etest), and 12 random amplified polymorphic DNA (RAPD)
      patterns (by arbitrarily primed polymerase chain reaction) were identified. The
      identical biotype, antibiogram, and RAPD pattern of the two isolates (one each
      from blood and bile) from a patient with biliary tract infection indicated the
      invasiveness of the organism. Two patients with intravascular catheter-related
      bacteremia had isolates of this organism repeatedly recovered, and these isolates
      had heterogeneous RAPD patterns. The present study highlights the wide
      distribution in hospital environments of various clones of S. paucimobilis, which
      may cause recurrent infections by a single strain or several episodes of
      infection due to two or more clones of this organism in hospitalized patients.

PMID- 9524844
TI  - Adjunctive corticosteroid therapy for patients whose treatment for disseminated
      Mycobacterium avium complex infection has failed.
AB  - Patients with AIDS and disseminated Mycobacterium avium complex (MAC) infection
      can have progressive disease despite combination antimycobacterial therapy. Our
      goal was to determine the utility of corticosteroids as adjunctive therapy for
      AIDS patients with disseminated MAC infection and refractory symptoms despite
      combination antimycobacterial therapy. We retrospectively reviewed 12 consecutive
      patients whose therapy for MAC infection clinically failed and who subsequently
      received low-dose oral corticosteroids in addition to continued combination
      antimycobacterial therapy. With the addition of corticosteroids, 11 of 12
      patients experienced a rapid improvement in symptoms, with diminished or resolved
      fevers and night sweats, and an increased sense of well-being and energy. Ten of
      12 patients gained weight; the differences between weights before and after
      steroid therapy were statistically significant (P = .003, paired Student's t
      test), and the weights achieved were similar to baseline weights prior to the
      development of MAC infection (P = .2). Mean survival after diagnosis of MAC
      infection was 17.5 months. New opportunistic processes developed in seven
      patients during corticosteroid therapy. However, given the severely
      immunocompromised status of these patients, it was not possible to attribute the
      development of new opportunistic processes directly to corticosteroid therapy.

PMID- 9524845
TI  - Are corticosteroids useful adjunctive agents in the treatment of disseminated
      Mycobacterium avium complex infection associated with human immunodeficiency
      virus infection?

PMID- 9524846
TI  - Infective endocarditis in solid organ transplant recipients.
AB  - Infective endocarditis, defined as pathologically or clinically definite by the
      Duke criteria, was observed in 14 transplant recipients at our institutions. In
      addition, we reviewed 32 previously reported cases in solid organ transplant
      recipients. The spectrum of organisms causing infective endocarditis was clearly
      different in transplant recipients than in the general population; 50% of the
      infections were due to Aspergillus fumigatus or Staphylococcus aureus, but only
      4% were due to viridans streptococci. Fungal infections predominated early
      (accounting for six of 10 cases of endocarditis within 30 days of
      transplantation), while bacterial infections caused most cases (80%) after this
      time. In 80% (37) of the 46 cases in transplant recipients, there was no
      underlying valvular disease. Seventy-four percent (34) of the 46 cases were
      associated with previous hospital-acquired infection, notably venous access
      device and wound infections. Three patients with S. aureus endocarditis had had
      an episode of S. aureus bacteremia > 3 weeks prior to the diagnosis of
      endocarditis and had received treatment for the initial bacteremia of < 14 days'
      duration. The overall mortality rate was 57% (26 of 46 patients died), with 58%
      (15) of the 26 fatal cases not being suspected during life. Endocarditis is an
      underappreciated sequela of hospital-acquired infection in transplant recipients.

PMID- 9524847
TI  - Inpatient emergencies encountered by an infectious disease consultative service.
AB  - The spectrum of infectious disease (ID) emergencies in hospitalized patients was
      assessed in a prospective study of 3,626 inpatient ID consultations in a 1,350
      bed teaching hospital. ID emergencies, defined by a need or anticipated need for
      advanced life support or by irreversible organ damage leading to permanent
      functional loss, were encountered in 175 patients. Infections of the central
      nervous system (26.3%), cardiovascular system (14.9%), alimentary system (13.1%),
      and lower respiratory tract (7.4%) and adverse reactions to antimicrobial agents
      (7.4%) were most common. In 18.9% of the cases, the referring clinicians were
      unaware of the emergency at the time of referral. Drug reactions (46.1%), severe
      alimentary and peritoneal infections (32.0%), upper respiratory tract infections
      (28.6%), and skin and soft-tissue infections (27.3%) were most frequently missed.
      The emergency ID conditions were not recognized because they had an atypical
      presentation (51.5%), were not commonly seen in the referring specialty (24.2%),
      were due to rare organisms (15.2%), or had unusual anatomical sites of
      involvement (9.1%). A close liaison between clinicians and the ID team is crucial
      for recognition of ID emergencies at their early stages so that appropriate
      investigations and management can be instituted expediently, before the
      occurrence of irreversible damage.

PMID- 9524848
TI  - Human herpesvirus-6 infection after liver transplantation.
AB  - A diagnosis of posttransplantation human herpesvirus-6 (HHV-6) infection was
      established for eight adult recipients among a liver transplantation patient
      population of 121. The diagnosis was based on serology and demonstration of HHV-6
      specific antigens in liver biopsy specimens with use of monoclonal antibodies and
      immunoperoxidase staining. A significant graft dysfunction was recorded in
      association with serodiagnosis. HHV-6 early antigens, as well as HHV-6 variant B
      antigens, were detected retrospectively in all six available liver biopsy
      specimens. Histologic examination of biopsy specimens demonstrated acute
      rejection in 5 of the 8 patients, and 3 patients had portal lymphocyte
      infiltration. In five cases cytomegalovirus (CMV) infection was associated with
      HHV-6 infection; in four cases CMV antigens were also detected in the biopsy
      specimens. Two patients who had pure HHV-6 infection without CMV infection or
      rejection had significantly impaired graft function, with a positive antigen
      detection test. Thus, HHV-6 may infect the liver allograft and cause graft
      dysfunction and may possibly be associated with rejection and/or CMV infection.

PMID- 9524849
TI  - Low plasma levels of adrenocorticotropic hormone in patients with acute
      influenza.
AB  - Plasma levels of adrenocorticotropic hormone (ACTH) and cortisol were measured in
      young adults with influenza virus type A (H3N2) infection for whom cultures were
      positive and in comparable controls without symptoms or other evidence of
      illness. The mean plasma ACTH level +/- SE in 19 patients with acute influenza
      was 13.5 +/- 2.1 pg/mL compared with 23 +/- 3.2 pg/mL in 11 controls (P = .02).
      Mean plasma ACTH levels +/- SE had risen to 21 +/- 4.1 pg/mL in specimens
      obtained from patients during convalescence. The mean plasma cortisol level +/-
      SE in patients with acute influenza was 13.7 +/- 1.4 micrograms/dL compared with
      10.8 +/- 1.0 micrograms/dL in controls (P = not significant). ACTH levels in
      individual controls were relatively higher than their cortisol levels, but ACTH
      levels in patients tended to be lower than cortisol levels in paired specimens.
      These findings suggest that influenza virus type A infection may have an
      inhibitory effect on the production or release of ACTH.

PMID- 9524850
TI  - The significance of vitamin A and carotenoid status in persons infected by the
      human immunodeficiency virus.
AB  - Hyporetinemia is associated with increased childhood morbidity and mortality that
      is reversible with vitamin A supplementation. Although vitamin A deficiency is
      otherwise rare in developed countries, the prevalence of hyporetinemia in human
      immunodeficiency virus (HIV)-infected persons is up to 29%. Hyporetinemic HIV
      infected patients have a 3.5-5-fold increased risk of death. Furthermore, HIV
      infected patients with very low or very high intake of vitamin A and beta
      carotene (a vitamin A precursor) have greater rates of disease progression than
      do patients with intermediate intake. In developing countries up to 60% of HIV
      infected pregnant women are hyporetinemic. In such women the relative risk of
      perinatal HIV transmission may be increased more than fourfold. These data
      indicate that vitamin A deficiency is common in HIV-infected patients in the
      developed world and strongly suggest that vitamin A supplementation may be
      especially useful in adjunctive therapy for HIV-infected pregnant women who
      reside in the developing world.

PMID- 9524851
TI  - Role of infection as a risk factor for atherosclerosis, myocardial infarction,
      and stroke.
AB  - An increasing body of evidence has linked infections to atherosclerosis and
      thrombosis. Herpesviruses cause atherosclerosis in experimental animals.
      Herpesviruses can also be detected in atherosclerotic lesions in humans.
      Cytomegalovirus may play a role in arteriosclerosis in transplanted hearts, and
      this virus, together with tumor suppressor protein p53, can be found in
      restenosis lesions following angioplasty. Chlamydia pneumoniae and dental
      infections are associated with coronary heart disease in cross-sectional and
      longitudinal studies, and preceding respiratory infections are associated with
      ischemic stroke. Infections may favor formation of atherosclerosis and thrombosis
      by elevation of blood levels of fibrinogen, leukocytes, clotting factor, and
      cytokines and by alteration of the metabolism and functions of endothelial cells
      and monocyte macrophages. Low-grade infections may also be one of the causes of
      the inflammatory reaction observed in atherosclerotic lesions and acute ischemic
      symptoms, reflected in elevated levels of C-reactive protein. These observations
      warrant further studies in this field.

PMID- 9524852
TI  - Infectious complications of body piercing.
AB  - Body piercing appears to be gaining in popularity and social acceptance. With the
      increase in the number of piercings, it is likely that health care providers may
      see an increase in the complications resulting from these piercings. These may
      include the transmission of hepatitis viruses and bacteria at the time of the
      piercing or in the course of wound care. We review the infectious complications
      that have resulted from body piercing and have been documented in the medical
      literature.

PMID- 9524853
TI  - Role of the microbiology laboratory in the diagnosis of lower respiratory tract
      infections.
AB  - The appropriate use of the clinical microbiology laboratory for diagnosing lower
      respiratory tract infections is controversial. As in clinical care, it is crucial
      to categorize the presenting illness properly as acute bronchitis, an acute
      exacerbation of chronic bronchitis, community-acquired pneumonia, or nosocomial
      pneumonia if diagnostic efforts to establish a microbial etiology are to be
      productive for the individual patient and affordable to society. The greatest
      potential benefit of microbiological investigations lies in the etiologic
      diagnosis of pneumonia. For community-acquired pneumonia, evaluation of a gram
      stained smear of sputum in terms of both quality and microorganisms present can
      help guide initial therapy as well as aid interpretation of subsequent culture
      results. As discussed in this review, the role of the clinical microbiology
      laboratory in the etiologic diagnosis of nosocomial and complicated pneumonias is
      more extensive and, in addition to evaluation of respiratory secretions, may
      include cultures of blood, pleural fluid, and specimens obtained by bronchoscopy.
      However, a prerequisite for the use of all currently available tests is their
      deployment for patients with clinical and radiographic evidence of pneumonia.

PMID- 9524854
TI  - Vertebral osteomyelitis due to Rhodococcus equi in a liver transplant recipient.
AB  - Rhodococcus equi is a rare but well-documented cause of cavitary pneumonia in
      immunocompromised patients. In this report the first case of R. equi infection
      manifesting as vertebral osteomyelitis is described. A 39-year-old liver
      transplant recipient presented with recurrent pneumonia and a pleura-based lung
      abscess and subsequently developed osteomyelitis of the lower thoracic spine.
      Surgical debridement and prolonged treatment with rifabutin and clarithromycin
      resulted in clinical cure. In the literature, 12 other cases of R. equi infection
      in solid-organ transplant recipients have been reported. Ten of these patients
      had documented pulmonary disease and seven had extrapulmonary manifestations.
      Prolonged antibiotic therapy and surgical drainage resulted in clinical
      improvement in > 90% of the reported cases.

PMID- 9524855
TI  - Cytomegalovirus infection is a risk factor for invasive aspergillosis in lung
      transplant recipients.
AB  - Invasive aspergillosis (IA) remains a major cause of morbidity and mortality
      following solid organ transplantation. To assess the incidence of IA following
      lung transplantation and to identify risk factors for its occurrence, we
      performed a case-control study involving 101 patients undergoing lung
      transplantation at our institution from 1990 to 1995 and reviewed the findings.
      Fourteen patients (14%) developed IA. The mean time from transplantation to
      diagnosis was 15 months. Nine patients died; the mean time to death from
      diagnosis was 13 days. Risk factors associated with developing IA included
      concomitant cytomegalovirus (CMV) pneumonia or viremia and culture isolation of
      Aspergillus species from a respiratory tract specimen after lung transplantation.
      Optimal strategies to prevent IA in lung transplant recipients remain to be
      determined, but prevention of aspergillus airway colonization and CMV viremia and
      disease after transplantation may be important targets for prophylactic
      interventions.

PMID- 9524856
TI  - Resolution of Mycobacterium avium complex bacteremia following highly active
      antiretroviral therapy.

PMID- 9524857
TI  - Fungemia due to Hormonema dematioides following intense avian exposure.

PMID- 9524858
TI  - Spontaneous breast abscess due to Mycobacterium fortuitum.

PMID- 9524859
TI  - Intestinal tuberculosis with associated coloduodenal fistula.

PMID- 9524860
TI  - Purulent pericarditis with associated cardiac tamponade caused by a Streptococcus
      pneumoniae strain highly resistant to penicillin, cefotaxime, and ceftriaxone.

PMID- 9524861
TI  - Unusual route of transmission for Brucella abortus.

PMID- 9524862
TI  - Detection of Francisella tularensis in clinical specimens by use of polymerase
      chain reaction.

PMID- 9524863
TI  - Nonresolving pneumonia due to Klebsiella oxytoca: an unusual presentation.

PMID- 9524864
TI  - Evaluation of the computer program GIDEON (Global Infectious Disease and
      Epidemiology Network) for the diagnosis of fever in patients admitted to a
      medical service.

PMID- 9524865
TI  - Possible transmission of human immunodeficiency virus type 1 from body piercing.

PMID- 9524866
TI  - Infective endocarditis associated with fiberoptic bronchoscopy in a patient with
      mitral-valve prolapse.

PMID- 9524867
TI  - Candida lusitaniae: an uncommon cause of prosthetic valve endocarditis.

PMID- 9524868
TI  - Splenic abscess caused by Propionibacterium avidum as a complication of cardiac
      catheterization.

PMID- 9524869
TI  - Inducement of Neisseria meningitidis resistance to ampicillin and penicillin in a
      patient with meningococcemia treated with high doses of ampicillin.

PMID- 9524870
TI  - There is no evidence that the free-living ameba Hartmannella is a human parasite.

PMID- 9524871
TI  - Additional cases of herpes simplex virus hepatitis.

PMID- 9524872
TI  - Disseminated bacille Calmette-Guerin disease after vaccination.

PMID- 9524873
TI  - Factors influencing time to sputum conversion among patients with smear-positive
      pulmonary tuberculosis.

PMID- 9524874
TI  - Neuropsychologic effects of carotid endarterectomy.
AB  - This study assessed neuropsychologic changes after internal carotid
      endarterectomy using a design that limited the confounding effects of surgical
      and anesthesiological stress. Twenty-eight patients (mean age = 65.9 years, SD =
      8.4, range 45-79), underwent extensive neuropsychological assessment before and
      on the seventh day after carotid endarterectomy for symptomatic carotid stenosis
      greater than 75%. A similarly assessed control group of 30 patients underwent
      elective orthopaedic surgery. A third cognitive assessment was performed 4 months
      postoperatively on a subgroup of the study patients. No significant cognitive
      change occurred in the control group. The study patients showed significant
      improvement in verbal memory, constructive abilities, verbal attainment, and
      visual attention; a trend towards further improvement of verbal functions was
      evident at the late postoperative assessment. No side-specific cognitive change
      was observed. In conclusion, carotid endarterectomy performed for currently
      accepted indications significantly improves several cognitive functions.

PMID- 9524875
TI  - Composite neuropsychological batteries and demographic correction:
      standardization based on equivalent scores, with a review of published data. The
      Italian Group for the Neuropsychological Study of Ageing.
AB  - Equivalent Scores (ES; Capitani & Laiacona, 1988) is a 5-point scale that offers
      a solution to the problem of standardizing neuropsychological scores after
      adjustment for age and education, given that the common z-standardization is not
      generally applicable in these cases. ES are discussed, and their properties and
      limits are compared with those of z-standardization. In a battery of ES
      standardized tests, the average ES (AES) for the whole battery can provide a
      measure of the overall cognitive level, free of the influence of age and
      education. We report empirical data from a battery composed of 10 ES-standardized
      tests, in order to discuss general properties of ES standardization. The expected
      mean of the AES is constant, regardless of the number or type of tests included.
      The standard deviation of the AES, however, is variable: it decreases in
      proportion to the number of tests, but increases in proportion to their
      intercorrelation. We provide general indications concerning the normality
      threshold, which are applicable to all batteries of ES-standardized tests
      regardless of the number and type.

PMID- 9524876
TI  - Neuropsychological aspects of multiple sclerosis: a quantitative review.
AB  - Neuropsychological studies of multiple sclerosis (MS) from a 20-year period were
      reviewed using meta-analytic and vote-count techniques. Mean effect sizes
      comparing MS and healthy control groups on variables categorized by
      neuropsychological domain were small to moderate in magnitude; all were
      statistically significant (M(r) = .22 (.13) to .46 (.15), rW = .23 to .43, all p
      < .05). Interhemispheric transfer, general cognitive ability, and learning/memory
      were more highly related to MS than were visuoperceptual, visuospatial, and
      visuoconstructional ability, language and conceptual ability (all p < .05); other
      domains were generally intermediate. Despite previous reports to the contrary,
      disease subtype was not shown to be consistently related to neuropsychological
      status independently of other potential explanatory variables. Findings were
      interpreted with regard to future research and clinical activities involving
      patients with MS, including selection of tests for brief neuropsychological
      screening examinations.

PMID- 9524877
TI  - Predicting premorbid neuropsychological functioning following pediatric traumatic
      brain injury.
AB  - This study examined the prediction of premorbid neuropsychological functioning
      using data from an ongoing prospective study of traumatic brain injuries (TBI) in
      children ages 6 to 12 years. Prediction equations were derived based on 80
      children with orthopedic injuries (OI), who served as a comparison group for the
      children with TBI. Collectively, parent ratings of premorbid school performance,
      maternal ethnicity, family socioeconomic status, and children's word recognition
      skill predicted from 13% to 45% of the variance in three measures of
      neuropsychological functioning. The regression equations were used to compute
      predicted scores among 109 children with TBI. Actual scores fell significantly
      below predicted scores among children with TBI, and the magnitude of the deficits
      was correlated with injury severity. Premorbid neuropsychological functioning can
      be predicted in children with TBI, but with less precision than would be
      desirable for clinical purposes.

PMID- 9524878
TI  - Reduced cognitive functions in a group of whiplash patients with demonstrated
      disturbances in the posture control system.
AB  - Past studies examining whether or not cognitive changes actually have occurred as
      a result of a whiplash (WL) accident have produced varying results. The aim of
      this study was to identify possible cognitive dysfunctions in a group with
      persistent problems after whiplash due to injuries to the posture control system
      and related structures. The whiplash subjects (n = 23) were selected on the basis
      of their reduced gain in the Smooth Pursuit Neck Torsion test (SPNT). The WL
      group differed significantly from a closely matched control group on tests of
      learning and memory, and prolonged divided attention and concentration. After
      attempting to rule out other ways of interpreting these differences (such as
      pain, depression, medication, and premorbid health problems), these data were
      interpreted as lending support to the notion of a causal connection between the
      disturbed posture control system and some cognitive malfunctions.

PMID- 9524879
TI  - Speed of motor execution and apraxia.
AB  - We used a reaction time paradigm to explore the relationship between motor
      execution and apraxia. The task required reaching for one to three keys. The
      instruction was varied by introducing a model of a hand indicating which fingers
      to use. Whereas patients with right-brain damage were slower than controls
      regardless of condition, the performance of patients with left-brain damage was
      only impaired when movements had to be carried out according to the model.
      Although this indicates a deficit in movement planning, there was no correlation
      between the impairment of patients with left-brain damage and clinical
      manifestations of apraxia. It thus remains an open question whether the
      impairment reflects an aspect of motor dominance of the left hemisphere that is
      too subtle to be detected by clinical apraxia testing, or whether it is related
      to task demands outside the domain of motor control. In any case, the results of
      this study demonstrate the need to control cognitive task demands when exploring
      motor capabilities of patients with left-brain damage.

PMID- 9524880
TI  - Deterioration of generic knowledge in patients with Alzheimer's disease: evidence
      from the Number Information Test.
AB  - Semantic memory for generic knowledge was assessed in patients with probable
      Alzheimer's disease (AD; n = 142) and elderly normal control (NC; n = 78)
      subjects using the Number Information Test (NIT), a test that consists of 24
      general knowledge questions that require a single number for an answer (e.g.,
      "How many days are in a year?"). The results showed that patients with AD were
      impaired, even in the mildest stage of dementia, and that this impairment grew as
      the severity of their dementia increased over time. In addition, patients with AD
      were highly consistent in the individual items they missed in subsequent test
      sessions conducted 1 or 2 years later. These results indicate that semantic
      memory for generic knowledge is impaired relatively early in AD, deteriorates
      throughout the course of the disease, and may be due to a loss of knowledge
      rather than to a retrieval deficit.

PMID- 9524881
TI  - Relationship between confabulation and measures of memory and executive function.
AB  - Confabulation has traditionally been attributed to a combination of memory
      impairment and executive dysfunction, but recent models propose that
      confabulation can result from executive dysfunction alone. One hundred and ten
      patients with diverse neurologic and psychiatric diagnoses were subdivided into
      high-, low-, and non-confabulator groups based upon the ratio of confabulations
      to total responses produced during story recall. Consistent with the combined
      deficit model, high-confabulators performed significantly worse than the low- and
      non-confabulators on measures of memory and measures of executive function that
      assess sustained attention, mental tracking, and set-shifting ability. However,
      there were no differences between groups on measures of problem-solving, concept
      formation, and verbal fluency, suggesting a dissociation in executive functions
      that contribute to confabulation.

PMID- 9524882
TI  - Variable memory profiles in Parkinson's disease.
AB  - Thirty-nine patients with Parkinson's disease (PD) were categorized into one of
      three subgroups using discriminant function analysis and three key indices from
      the California Verbal Learning Test (CVLT). Patients were classified as having
      one of three memory profiles: (a) a normal memory profile; (b) a memory profile
      often observed in patients with Huntington's disease (HD); or (c) a memory
      profile often observed in patients with Alzheimer's disease (AD). Twenty of the
      patients with PD were classified as having a normal profile, 10 as having an HD
      profile, and 9 as having an AD profile. The three subgroups did not differ on
      measures of global cognitive functioning, letter fluency, confrontation naming,
      or visuo-construction, suggesting that the patients with PD with an AD memory
      profile were not experiencing AD, per se. These results demonstrate that the
      memory deficits associated with PD can be similar to those found in patients with
      either HD or AD, and argues against the notion that the behavioral manifestations
      of PD are homogeneous.

PMID- 9524883
TI  - Use of the odds ratio to translate neuropsychological test scores into real-world
      outcomes: from statistical significance to clinical significance.
AB  - Standard parametric tests generate p values and effect sizes, but often these are
      difficult to translate into real-world outcomes. In this study, the odds ratio
      was applied to neuropsychological testing and was compared to parametric
      approaches. Participants were 26 community-dwelling adults with possible or
      probable Alzheimer's disease and 25 matched healthy community-dwelling
      volunteers. Odds ratios were computed to estimate the probability of concurrent
      diagnosis given neuropsychological performance level. Odds ratios discriminated
      the groups at magnitudes that could not be discerned from t-test significance
      tables. These values were compared to sensitivity, specificity, and overall
      accuracy. Clinical and research applications and implications were addressed.

PMID- 9524884
TI  - Psychometric properties and factor structure of the Wechsler Memory Scale-Revised
      in a sample of persons with intractable epilepsy.
AB  - The Wechsler Memory Scale-Revised (WMS-R) is used routinely as a presurgical
      assessment of memory for clients considering elective resection of the temporal
      lobe and/or hippocampus for the relief of intractable temporal lobe epilepsy.
      This research investigated the psychometric properties of the WMS-R in a
      population of people with epilepsy. The sample consisted of 181 patients with a
      diagnosis of epilepsy who underwent a complete neuropsychological examination as
      a routine part of their investigation. The results confirm that the WMS-R has
      acceptable levels of reliability as measured by internal consistency. A factor
      analysis revealed a consistent three-factor structure: Visual Memory, Verbal
      Memory, and Attention/ Concentration factors. Multiple regression analysis,
      however, indicated that the Visual Memory index was susceptible to a number of
      influences, throwing into question whether it is a pure measure of nonverbal
      memory functioning.

PMID- 9524885
TI  - Neuropsychological function and diurnal variation in depression.
AB  - Twenty-six patients suffering from DSM-III-R major depressive episode with
      diurnal variation of mood were examined at approximately 8 AM and 8 PM, using a
      neuropsychological test battery. We found that tests of executive function,
      especially the verbal fluency test, were sensitive measures of diurnal variation,
      but that personality measures were relatively robust in that they were not
      significantly affected by diurnal variations of mood. The relevance of detecting
      and assessing diurnal changes of mood with reliable, objective measures of
      performance is discussed.

PMID- 9524886
TI  - Postdicting verbal IQ of elderly individuals.
AB  - We undertook a longitudinal crossvalidation of the Ryan and Paolo (1992)
      equation's ability to postdict Wechsler Adult Intelligence Scale-Revised (WAIS-R)
      Verbal IQ (VIQ) from National Adult Reading Test (NART) performance measured 5
      years after VIQ scores were obtained, for a sample of 49 elderly normal
      individuals (mean age 71 years). Five-year interval postdiction accuracy agreed
      very well with the results of the original, concurrent study. Clinical utility is
      still limited, however, as VIQ must decline by 16.3 points for 95%-detection
      sensitivity. A new regression equation that utilizes a combination of NART errors
      and WAIS-R Vocabulary age-scaled scores (measured 3 years earlier) provided
      slightly better expected clinical sensitivity and accounted for 49% of the
      variance in VIQ scores.

PMID- 9524887
TI  - The 60-item Boston Naming Test: norms for cognitively intact adults aged 25 to 88
      years.
AB  - Age- and education-stratified norms on the 60-item Boston Naming Test (BNT) are
      presented for 219 cognitively intact adults aged 25-88 years. The sample size,
      age range, and education levels of this sample represent an improvement over
      currently available norms. Eight short forms of the BNT are compared with the 60
      item BNT. Frequency of errors for individual BNT items and the distribution of
      incorrect responses over seven different categories of errors are discussed.
      Finally, specific probes to overcome difficulties with ambiguous items are
      suggested.

PMID- 9524888
TI  - Wisconsin Card Sorting Test dimensions in schizophrenia: factorial, predictive,
      and divergent validity.
AB  - This study explored the factor structure of the Wisconsin Card Sorting Test
      (WCST). Scores from 197 participants with schizophrenia or schizoaffective
      disorder were subjected to an exploratory factor analysis that yielded three
      factors: Perseveration, Nonperseverative Error, and Inefficient Sorting.
      Comparison with two previous factor analyses revealed remarkable factorial
      invariance. Correlations with subject and illness characteristics, symptom
      dimensions, and work performance demonstrated predictive and divergent validity
      for the three factors. However, a representative item from each factor yielded
      similar correlations with very little loss of power suggesting that the factors
      are composed of highly redundant items. When data reduction is necessary,
      schizophrenia researchers are justified in using three variables: perseverative
      error, nonperseverative error, and failure to maintain set, to represent WCST
      performance.

PMID- 9524889
TI  - CVLT recognition-recall discrepancies and methodological rigor: a reply.

PMID- 9524890
TI  - Is a patient's history of food supplement use simply supplementary?

PMID- 9524891
TI  - Evaluation of simethicone for the treatment of postoperative abdominal discomfort
      in infants.
AB  - STUDY OBJECTIVE: To determine whether abdominal discomfort is a cause for
      distress symptoms in infants following administration of inhalational anesthesia,
      and to evaluate the effectiveness of simethicone in treating this discomfort.
      DESIGN: Randomized, double-blinded study. SETTING: Large tertiary care,
      university-based medical center. PATIENTS: 175 ASA physical status I and II
      infants under 28 months of age who underwent an inhalational anesthetic for a
      variety of procedures that were expected to cause relatively little pain.
      INTERVENTIONS: Children were assessed for the presence of postoperative abdominal
      discomfort, and, if evident, were randomly given either simethicone or placebo in
      a double-blinded fashion. MEASUREMENTS AND MAIN RESULTS: Abdominal discomfort was
      measured using the Faces Legs Activity Cry and Consolability (FLACC) Behavioral
      Pain Scale. Scores were recorded pre-drug; at 10, 20, and 30 minutes following
      drug administration; and at discharge. If discomfort had not resolved within 15
      minutes after the drug was given, routine analgesics or other medications were
      administered. Abdominal girth was measured preoperatively, on admission into the
      postanesthesia care unit (PACU), and at discharge. 21% of infants exhibited
      symptoms of abdominal discomfort postoperatively. Younger infants were at greater
      risk for this condition. 36 infants were given either placebo or simethicone, and
      of these, infants who received simethicone were comfortable earlier and required
      fewer rescue medications compared with placebo. There were no differences in
      ability to tolerate oral fluids prior to discharge or in the length of stay in
      the PACU. CONCLUSIONS: Simethicone is a safe and inexpensive medication that may
      provide anesthesiologists with an effective treatment choice for suspected
      postoperative abdominal discomfort in infants.

PMID- 9524892
TI  - Pulmonary aspiration in pediatric patients during general anesthesia: incidence
      and outcome.
AB  - STUDY OBJECTIVES: To determine the incidence of, outcome of, and risk factors for
      anesthesia-related pulmonary aspiration in the predominantly pediatric population
      receiving anesthesia care. DESIGN: Using a clinical concurrent quality assessment
      system we developed, we used data stored in a custom-designed computerized
      database to initiate a retrospective review. Statistical relationships were
      analyzed by Fisher's exact test and binary logistic regression with commercially
      available software. SETTING: University-affiliated pediatric hospital. PATIENTS:
      All patients receiving anesthesia (n = 50,880) between April 1, 1988, and March
      31, 1993. MEASUREMENTS AND MAIN RESULTS: Aspiration occurred in 52 (0.10% or 10.2
      per 10,000) of the 50,880 general anesthesia cases. Aspirate was food or gastric
      contents in 25 cases (0.049% or 4.9 per 10,000), blood in 13 (0.026% or 2.6 per
      10,000), and unknown material in 14 (0.0275% or 2.76 per 10,000). There were no
      deaths attributable to aspiration. Morbidity was confined to unanticipated
      hospital admission (n = 12), cancellation of the surgical procedure (n = 4), and
      intubation, with or without ventilation (n = 15). Aspiration occurred
      significantly more often in patients with greater severity of underlying illness
      (ASA physical status III or IV) (p = 0.0015), intravenous induction (p = 0.0054),
      and age equal to or greater than 6.0 years and less than 11.0 years (p = 0.0029).
      Emergency procedures had a marginally significant increased aspiration risk (p =
      0.0527). CONCLUSIONS: The overall incidence of anesthesia-related aspiration in
      our series (0.10%) was twice that reported in studies of adults, and four times
      (0.25%) higher for those at highest risk (ASA physical status III or IV vs.
      physical status I or II). Anesthesia-related pulmonary aspiration was proven to
      be a rare event in this tertiary pediatric center and its consequences relatively
      mild. Because of the very low frequency and the lack of serious outcome after
      aspiration in ASA physical status I and II pediatric patients, it appears that
      routine prophylactic administration of histamine blockers or propulsive drugs in
      healthy pediatric patients is unwarranted.

PMID- 9524893
TI  - Effects of split torso positioning and laparoscopic surgery for donor nephrectomy
      on respiratory mechanics.
AB  - STUDY OBJECTIVE: To test whether split torso positioning, abdominal insufflation,
      and other procedures performed during laparoscopic nephrectomy would affect
      mechanical impedances to inflation [i.e., elastance (E) and resistance (R) of the
      total respiratory system (Ers, and Rrs), lungs (EL and RL), and chest wall (Ecw
      and Rcw)] differently from previously studied laparoscopic procedures. DESIGN:
      Unblinded study, each patient serving as own control. SETTING: University
      hospital. PATIENTS: 12 ASA physical status I and II patients scheduled for
      laparoscopic donor nephrectomy, all without cardiopulmonary disease.
      INTERVENTIONS: Patients were anesthetized and paralyzed, tracheally intubated and
      mechanically ventilated at 10, 20, and 30 breaths/minute and at tidal volumes of
      250, 500, and 800 ml. Measurements were made in the following positions: supine,
      split torso, abdominal insufflation (Pab = 15 mmHg), and supine after deflation.
      MEASUREMENTS AND MAIN RESULTS: Airway flow and pressure and esophageal pressure
      were measured. Discrete Fourier transformation was used to calculate E and R.
      These were analyzed with repeated measures, linear multiple regression with
      accepted level of significance at p < 0.05. Ers, Ecw, and Rcw increased (p <
      0.05) while EL decreased (p < 0.05) when patients changed from supine to split
      torso. During Pab = 15 mmHg, Ers, Ecw, and Rcw increased further and Rrs and RL
      increased (p < 0.05). Following abdominal deflation, Ecw and Ers remained
      elevated (p < 0.05). The changes in Ecw caused by laparoscopy and surgery were
      greater than we have previously measured in other laparoscopic procedures, while
      the changes in EL were less. CONCLUSIONS: Laparoscopic nephrectomy affects lung
      and chest wall mechanical properties differently from other laparoscopic
      procedures. This finding could be due to the split torso positioning, and the
      effects of abdominal swelling on the chest wall caused by administration of more
      perioperative fluids with laparoscopic nephrectomy.

PMID- 9524894
TI  - The use of near-infrared cerebral oximetry in awake carotid endarterectomy.
AB  - STUDY OBJECTIVE: To determine the utility of cerebral oximetry for monitoring the
      adequacy of cerebral blood flow (CBF) during carotid cross-clamp. DESIGN:
      Prospective study. SETTING: University hospital. PATIENTS: 16 consecutive ASA
      physical status III (or higher) patients for awake carotid endarterectomy (CEA).
      INTERVENTIONS: Regional cerebral oxygen saturation (SaO2) was monitored
      continuously during CEA, which was performed by the same surgeon, and with
      standard regional anesthetic, sedation, monitoring, and operative techniques.
      Data were recorded and analyzed using repeated measures analysis of variance
      (ANOVA). MEASUREMENTS AND MAIN RESULTS: 14 hemodynamically stable patients
      demonstrated significant decreases in cerebral SaO2 from baseline: 69 + 1.8% to
      64 + 1.2% at carotid cross-clamp (p < 0.001). After 5, 10, and 15-minute cross
      clamp time, cerebral SaO2 was 63 + 1.4%, 64 + 1.5%, and 63 + 1.4%, respectively
      (p < 0.001, vs. baseline). On cross-clamp removal, cerebral SaO2 rose
      significantly: 67 + 1.6% (p < 0.01 vs. 5, 10, and 15 min). Two hypotensive
      patients (mean arterial pressures of 40 and 43 mmHg) developed signs and symptoms
      of global cerebral ischemia, with a concomitant decrease in cerebral oximetry
      (40% and 48%, respectively). These changes resolved with correction of
      hypotension. CONCLUSION: Cerebral SaO2 decreased significantly on carotid cross
      clamp in patients undergoing awake CEA. Hemodynamically stable patients
      demonstrated no evidence of regional brain failure when SaO2 decreased to 63%
      (mean decrease of 7.2%). Two hemodynamically unstable patients had evidence of
      global brain failure when SaO2 was less than 48% (mean decrease of 36%). Our
      findings suggest that cerebral oximetry reflects CBF, and it may be an effective,
      noninvasive method of monitoring regional cerebral oxygenation changes during
      CEA. Significant reductions in regional SaO2 may be tolerated without evidence of
      brain failure. Further studies are needed to define an SaO2 threshold that
      reflects regional brain failure.

PMID- 9524895
TI  - Induction of anesthesia by titration of eltanolone compared with thiopental and
      etomidate for coronary artery bypass grafting.
AB  - STUDY OBJECTIVE: To evaluate whether induction of anesthesia with eltanolone in
      coronary artery bypass graft (CABG) patients is associated with greater
      hemodynamic stability than either thiopental sodium or etomidate. DESIGN:
      Randomized, controlled study. SETTING: University hospital. PATIENTS: 75 ASA
      physical status III and IV patients scheduled for elective CABG over 18 years of
      age, with left ventricular ejection fraction over 30%. INTERVENTIONS: The
      participants were prospectively randomized into three groups, each group
      consisting of 25 patients. Anesthesia was induced by titration of either
      eltanolone, thiopental sodium, or etomidate. The end point was "loss of verbal
      contact." MEASUREMENTS AND MAIN RESULTS: Hemodynamic variables were recorded in
      the awake state, 2 minutes after induction, after administration of fentanyl 0.01
      mg/kg, and 2 and 5 minutes after intubation. After induction of anesthesia,
      cardiac index (CI) decreased from 2.6 +/- 0.5 to 2.2 +/- 0.5 Lxmin-1xm-2 in the
      eltanolone group and remained at this value throughout the study period in
      contrast to the control groups. After fentanyl was given, mean arterial pressure
      was significantly lower in the case of eltanolone (69 +/- 15 mmHg) compared with
      thiopental (81 +/- 19 mmHg) and etomidate (84 +/- 18 mmHg). Mean arterial
      pressure remained significantly lower at the points of measurement after
      intubation. Two minutes after intubation, CI was likewise significantly lower in
      the eltanolone group (2.2 +/- 0.4 Lxmin-1xm-2) compared with the thiopental group
      (2.7 +/- 0.7 Lxmin-1xm-2). CONCLUSIONS: Eltanolone produces more hemodynamic
      depression compared with etomidate and thiopental when administered in
      combination with fentanyl 10 micrograms/kg.

PMID- 9524896
TI  - Value of mild hypothermia in patients who have severe circulatory insufficiency
      even after intra-aortic balloon pump.
AB  - STUDY OBJECTIVE: To evaluate the effectiveness of mild hypothermia in postcardiac
      surgical patients with severe heart failure in spite of conventional medical
      therapy and the use of intra-aortic balloon pumping (IABP). DESIGN: Prospective,
      clinical study. SETTING: Teaching hospital. PATIENTS: 10 postcardiac surgical
      patients with severe heart failure despite the use of IABP with massive doses of
      catecholamine. INTERVENTIONS: Patients underwent mild hypothermia produced by
      surface cooling (to approximately 34.5 degrees C). Hemodynamic criteria for the
      induction of hypothermia included a cardiac index (CI) of less than 2.2 L/min/m2
      with a pulmonary capillary wedge pressure (PCWP) of up to 18 mmHg despite the use
      of IABP with massive doses of catecholamine. MEASUREMENTS AND MAIN RESULTS: After
      control measurements had been taken at normal core body temperature (37 degrees
      C), patients were cooled to approximately 34.5 degrees C (using a cooling blanket
      and gastric lavage with cold water) to decrease tissue oxygen (O2) demand.
      Patients showed significant improvements in CI (1.9 +/- 0.3 to 2.2 +/- 0.3
      L/min/m2), mixed venous O2 saturation, (SvO2; 55 +/- 7 to 64 +/- 6%), and urine
      output (2.1 +/- 1.1 to 3.4 +/- 2.2 ml/kg/hr). Patients were rewarmed while SvO2
      was being monitored. The duration of the hypothermia was 38 +/- 41 hours. Oxygen
      delivery increased in 8 of the 10 patients, the mean value (+/- SD) for the group
      rising from 309 +/- 65 ml/min/m2 to 358 +/- 57 ml/min/m2 as temperature was
      reduced from 36.7 +/- 0.4 degrees C to 34.7 +/- 0.3 degrees C. All patients were
      successfully weaned from IABP at 140 +/- 107 hours after admission to the
      intensive care unit. CONCLUSIONS: Mild hypothermia is a simple and useful
      procedure for improving the circulation of postcardiac surgical patients with
      severe heart failure despite the use of IABP.

PMID- 9524897
TI  - Altered reactivity to acetylcholine in the pulmonary circulation after
      cardiopulmonary bypass is part of reperfusion injury.
AB  - STUDY OBJECTIVE: To investigate whether a time sequence of acetylcholine (ACH)
      reactivity indicative of endothelial reperfusion injury could be demonstrated in
      the pulmonary circulation in patients after cardiopulmonary bypass (CPB). DESIGN:
      Prospective study. SETTING: Operating theater and intensive care unit of a
      university hospital. PATIENTS: 10 ASA physical status III and IV patients with
      ischemic or valvular heart disease. INTERVENTIONS: Pulmonary vascular resistance
      index (PVRI) was measured before and during an infusion of ACH. This procedure
      was done after induction of anesthesia but before surgery, immediately after
      weaning from bypass, and at 1 to 1.5 and 4 hours after CPB. MEASUREMENTS AND MAIN
      RESULTS: ACH caused a decrease in PVRI before (p < 0.01) and directly after CPB
      (p < 0.05) but not at 1 to 1.5 or 4 hours after bypass. CONCLUSIONS: The
      maintained reactivity to ACH directly after CPB, followed by no reaction at 1 to
      1.5 and 4 hours, was in agreement with experimental findings and indicates
      endothelial reperfusion injury caused by the period with no blood flow through
      the pulmonary artery during CPB and subsequent reperfusion.

PMID- 9524898
TI  - Power spectral heart rate analysis demonstrates decreased activity of the
      sympathetic nervous system during low bupivacaine spinal anesthesia.
AB  - STUDY OBJECTIVE: To evaluate the onset of spinal anesthesia with power spectral
      heart rate analysis to determine the influence of the block on the autonomic
      nervous system. DESIGN: Prospective, clinical evaluation. SETTING: Tertiary-care
      teaching hospital. PATIENTS: 27 ASA physical status I and II patients scheduled
      for lower extremity orthopedic surgery and free of major cardiac disease or
      cardiac drugs with direct influence of heart rate (HR) or blood pressure (BP).
      INTERVENTIONS: Prior to anesthesia, a baseline power spectral heart rate reading
      was taken in the supine position. Spinal anesthesia was established in the
      sitting position with 15 mg of bupivacaine and 0.2 mg epinephrine introduced at
      the L3-L4 interspace with a 22-gauge Quincke needle. The patient was returned
      supine, and power spectral heart rate data were again collected at 5-minute
      intervals throughout the procedure. Level of the spinal block was checked at 5
      minute intervals until 30 minutes and considered complete when two consecutive
      readings were unchanged. MEASUREMENTS AND MAIN RESULTS: Heart rate and BP were
      recorded at baseline and at five-minute intervals after injection. Power spectral
      heart rate data included low-frequency activity (LFa), high-frequency activity
      (HFa), and the ratio (LFa/HFa). Spinal level achieved was recorded by thoracic
      dermatome at complete onset. Heart rate and BP remained within 20% of control in
      all cases. Complete onset of the spinal block was present by 30 minutes in all
      cases. The average level of spinal anesthesia was T8. Compared with baseline, LFa
      activity decreased, HFa activity remained unchanged, and the ratio was decreased.
      During endoprosthesis insertion, 9 of 14 total hip patients had a transient ten
      fold increase in LFa activity, without HFa change, and a corresponding increase
      in the ratio. CONCLUSIONS: Power spectral heart rate analysis during low thoracic
      bupivacaine spinal anesthesia is compatible with decreased sympathetic activity
      during stable hemodynamic intervals. Insertion of hip endoprosthesis resulted in
      a dramatic, transient increase in sympathetic activity, indicating that
      sympathetic activation was still possible despite the presence of surgical
      anesthesia from the subarachnoid block.

PMID- 9524899
TI  - Systolic pressure variation predicts the response to acute blood loss.
AB  - STUDY OBJECTIVE: To evaluate systolic pressure variation (SPV), defined as the
      difference between the maximum and minimum systolic blood pressure measured
      during a controlled mechanical respiratory cycle, as a predictor of the cardiac
      output (CO) response to an acute decrease in ventricular preload. DESIGN:
      Prospective study with each subject serving as his or her own control. SETTING:
      Cardiac surgery operating rooms of a university medical center. PATIENTS: 15
      adults with good ventricular function undergoing coronary artery bypass grafting.
      INTERVENTION: During stable anesthetic conditions and before surgical
      stimulation, 500 ml of blood was removed from each patient over 10 minutes.
      MEASUREMENTS AND MAIN RESULTS: CO, central venous pressure (CVP), pulmonary
      artery diastolic pressure, and pulmonary artery occlusion pressure (PAOP), and
      SPV before and after phlebotomy were recorded. Phlebotomy was associated with
      significant decreases in CVP, PAOP, and CO, and an increase in SPV. Of these
      variables, SPV was the best predictor of the percent decrease in CO resulting
      from blood loss. CONCLUSION: SPV is a dynamic measurement, which, by revealing
      the response to small cyclical changes in left ventricular preload that occur
      during the controlled mechanical respiratory cycle, is a better predictor than
      central filling pressures of the response of CO to acute decreases in preload
      that occur as a result of acute blood loss.

PMID- 9524900
TI  - Recall of risks following labor epidural analgesia.
AB  - STUDY OBJECTIVE: To ascertain patients' recall of the risks of labor epidural
      analgesia from a discussion of informed consent during active labor. DESIGN:
      Survey analysis following an intervention. SETTING: Labor and delivery unit of a
      tertiary-care teaching hospital. PATIENTS: 101 ASA physical status I and II
      parturients in active labor. INTERVENTIONS: Patients were given a standardized
      discussion of the risks of labor epidural analgesia. MEASUREMENTS AND MAIN
      RESULTS: Within 24 hours of the informed consent discussion, patients were first
      asked to recall risks, and then asked to identify risks from a true and false
      list. Patients recalled 2.0 +/- 1.3 risks (mean +/- SD), with 12% recalling at
      least four risks, 37% recalling at least three risks, 66% recalling at least two
      risks, and 87% recalling at least one risk. There was no difference in level of
      recall between primiparas and multiparas, or in patients with mild and moderate
      pain scores versus those patients with severe pain scores. CONCLUSIONS: Recall of
      risks by parturients is similar to the recall of risks by other patients, and it
      does not appear to be affected by parity or the reported level of pain.

PMID- 9524902
TI  - The choice of anesthesia in Segawa's syndrome.
AB  - Segawa's syndrome is a rare hereditary progressive dystonia with diurnal
      fluctuation, which, in contrast to other types of chronic dystonia in children,
      responds dramatically to levodopa therapy. We present a case of a patient,
      suffering from Segawa's syndrome who underwent two cesarean sections, and we
      describe our experience in providing anesthesia to that patient. The first
      cesarean section was performed with general anesthesia, while the second was
      accomplished with epidural anesthesia. On both occasions the anesthesia was
      uneventful.

PMID- 9524901
TI  - Oral dolasetron mesylate for prevention of postoperative nausea and vomiting: a
      multicenter, double-blind, placebo-controlled study. The Oral Dolasetron PONV
      Prevention Study Group.
AB  - STUDY OBJECTIVE: To examine the safety and effectiveness of a range of single
      oral doses of dolasetron mesylate for the prevention of postoperative nausea and
      vomiting. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: 32
      hospitals. PATIENTS: 789 female ASA physical status I, II, and III patients, ages
      18 to 60 years, weighing between 45 and 100 kg, scheduled for major gynecologic
      surgery (including abdominal hysterectomy, gynecologic laparotomy, or vaginal
      hysterectomy) with general anesthesia. INTERVENTIONS: 25, 50, 100, or 200 mg oral
      doses of dolasetron mesylate or placebo were administered 1 to 2 hours before
      induction of anesthesia. Efficacy was assessed for 24 hours postrecovery by
      measuring complete response (no emetic episodes, no rescue medication), total
      response (complete response with no nausea), time to first emetic episode or
      rescue, and patient visual analog scale evaluations of nausea severity and
      satisfaction with antiemetic therapy. MEASUREMENTS AND MAIN RESULTS: Complete
      response rates for the 50, 100, and 200 mg dose groups were statistically greater
      than placebo (p < or = 0.018). Likewise, total response rates were statistically
      greater in the 50, 100, and 200 mg dose groups than in the placebo group (p =
      0.012). Percentage of patients with no nausea and patient satisfaction scores
      were significantly higher for each dolasetron dose group than placebo (p < or =
      0.047 and p < or = 0.004, respectively). Efficacy peaked at the 50 mg dose. The
      incidence of adverse events was similar in the placebo (30.1%) and dolasetron
      groups (29.4%). Headache was the most frequent treatment-related adverse event,
      with 2% to 5% incidence across groups. Incidence of adverse events did not
      increase with increasing dolasetron doses. Dose-related decreases in blood
      pressure at acute time points were not clinically significant. CONCLUSION: Single
      oral doses of dolasetron, administered 1 to 2 hours before induction of
      anesthesia, are safe and effective for preventing postoperative nausea and
      vomiting in this patient sample. Maximal antiemetic response was seen with the 50
      mg oral dolasetron dose.

PMID- 9524903
TI  - Increased tolerance to vecuronium in a patient with testicular feminization.
AB  - Muscle relaxant pharmacophysiology can be altered in various clinical situations.
      We report increased requirement of vecuronium in a patient diagnosed with
      testicular feminization. Increased level of endogenous testosterone and steroidal
      core structure of vecuronium may explain the increased tolerance to vecuronium in
      this patient.

PMID- 9524904
TI  - Nonsurgical extraction of intracardiac double-knotted pulmonary artery catheter.
AB  - A 75-year-old patient was admitted to the operating room for an emergency
      laparotomy for leaking abdominal aortic aneurysm. A pulmonary artery catheter
      (PAC) was inserted through the right internal jugular vein but it was impossible
      to advance the catheter lip into the pulmonary artery. We tried to withdraw the
      catheter but this was also impossible. A postoperative chest radiograph revealed
      a catheter knot in the right atrium. We succeeded in removing the PAC through a
      14-French sheath introducer placed in the femoral vein via fluoroscopy.

PMID- 9524905
TI  - Subcutaneous morphine is superior to intrathecal morphine for pain control in a
      patient with hypernephroma.
AB  - This case report illustrates differences in analgesia quality and morphine
      consumption between an intrathecal infusion and the subcutaneous instillation of
      morphine in a cancer patient with hypernephroma. Superior analgesia was obtained
      with a 450 mg dose of subcutaneous morphine [i.e., visual analog scale (VAS)
      score 0/10] than with 10 mg intrathecal morphine/day administered at the
      thoracolumbar (twelfth dorsal vertebra) level (VAS score 2/10). If the
      instillation occurs at the lumbosacral level (between the last lumbar and the
      first sacral vertebra), a dosage of 70 mg morphine/day cannot induce the same
      pain relief as 450 mg subcutaneous morphine (VAS score 5/10 vs. 0/10). In some
      cancer patients, subcutaneous morphine offers superior pain control than
      intrathecal morphine.

PMID- 9524906
TI  - Setting performance standards for an anesthesia department.
AB  - The Stanford University Department of Anesthesia established performance
      standards by identifying aspects of their service that were related to an
      important "customer's" perception of quality. A "quality grid" targeted service
      attributes that surgeons scored high for importance and low for performance.
      Control charts and flow charts helped establish reasonable performance levels for
      "timely first case starts" and "turnaround time." Control charts indicated that a
      reasonable performance standard for timely first case starts was "less than 20%
      of first case delays will be related to anesthesia activities." For turnaround
      time, the standard was set at "less than 10% of all turnaround times will be
      greater than 15 minutes, because of anesthesia-related activities." After
      instituting performance standards, the performance for first case start times
      improved from a 36% defective rate to a 9% defective rate. Anesthesia-related
      delays in turnaround times stabilized at a 16% defective rate. Using appropriate
      service standards can improve performance.

PMID- 9524907
TI  - Biological dyes may improve the safety of local anesthetics.

PMID- 9524908
TI  - Guidelines for every person.
AB  - Guidelines, it is assumed in health care circles, have worth. In the ideal health
      care system they may offer everything from medical certainty to legal protection.
      They have the potential to save practitioners from the trauma of indecision and
      at the same time protect them from the consequences of wrong decisions. In this
      paper, I discuss the impact of guidelines on general practitioners and consumers.
      Both groups are at the effector end where guidelines should have maximal impact.
      It is primarily medical practitioners and their constituents in the long run that
      have to make guidelines work. Theoretical questions about the essential worth of
      guidelines for consumers and general practitioners are explored, as well as the
      more practical issues of utility of guidelines. My hypothesis is that guidelines
      may be conceptually worthwhile, but as yet are of unproven utility. This argument
      is traced through the literature surrounding the involvement of general
      practitioners and consumers in guideline development, implementation, review and
      relevance. From this information a new role for guidelines which is cogniscent of
      the needs and circumstances of the end users is postulated. Guidelines can become
      the basis for the principles of sound clinical practice which allow for the
      unique individual circumstances of clinical practice whilst also providing a
      consolidated basis for this practice.

PMID- 9524909
TI  - 'Best clinical practice': assessment of processes of care and of outcomes in the
      US Military Health Services System.
AB  - The National Quality Management Program of the Military Health Services System of
      the United States has undertaken a series of projects whose objective is the
      active, on-going monitoring and improvement of the effectiveness and efficiency
      of the care provided to a broad population that encompasses troops on active
      duty, retirees and dependents. The analytic activities consist of (1)
      identification by clinical panels of conditions and procedures of interest; (2)
      collection of data from electronic repositories and from charts to characterize
      the patients, how they are managed, the clinical outcomes they experience, the
      resource costs their care entails, and, from questionnaires, their functional
      status and level of satisfaction, and (3) generation of 'report cards' that
      inform organizational units down to the level of the hospital of the
      characteristics of their patients, their practices, and the risk-adjusted
      outcomes they achieve. The patterns of care employed by the hospitals that obtain
      the best risk-adjusted outcomes and resource utilization ('best clinical
      practice') are identified and made known. In addition, (4) a systematic process
      of developing outcomes-based practice guidelines has been devised. It intent is
      to serve as a decision-support tool for clinicians. Initial estimates have been
      obtained of the probable consequences of the application of this tool to
      operative interventions in childbirth. Use of the tool would result in a higher
      occurrence of elective Caesarean sections, a reduced rate of emergency Caesarean
      sections and much lower use of forceps, with an overall improvement in outcomes
      and lower resource costs. This program is currently in the early phases of
      implementation. The two principal requirements for the immediate future are (1)
      education of the clinical and administrative communities in the use of the data
      and the decision-support tools and (2) evaluation of the consequences of the use
      of the data by the clinical and administrative communities.

PMID- 9524910
TI  - Beyond health outcomes: the advantages of measuring process.
AB  - The use of process measures in the assessment of the quality of care has been
      neglected of late. The outcomes movement has gathered momentum and process
      measurement appears to have been left trailing in the wake. Yet process measures
      can be sensitive indicators of the quality of care and have many advantages over
      outcomes. They are readily measured and can easily be interpreted; comparisons
      are not essential (as they are with outcomes monitoring) but even if used they
      are little bothered by the case-mix arguments which bedevil outcomes assessment.
      Further, the direct measurement of process can directly indicate deficiencies of
      care which need to be remedied. Finally, there are some aspects of care which are
      only amenable to study using measures of process. These benefits come at a price:
      first there must be good evidence that links the processes of care to desirable
      outcomes. This paper explores the advantages of measuring processes of care in
      quality assessment and advocates a balanced approach to the process vs. outcome
      debate.

PMID- 9524911
TI  - Developing a quality of care index for outpatient methadone treatment programmes.
AB  - This article describes the development and evaluation of a psychometric
      instrument for assessing quality of care in outpatient methadone substitution
      therapy (MST) programmes. The instrument, termed the Quality of Care Index-1 (QCI
      1), is a seven-item scale evaluated in two studies. Its psychometric properties
      are consistently acceptable across both studies. The QCI-1 reveals three distinct
      quality criteria relevant to the condition of the patients in methadone
      treatment. These are drug use hygiene, sharing of injecting equipment and
      partner's drug use status.

PMID- 9524912
TI  - Snyder v. American Association of Blood Banks: a re-examination of liability for
      medical practice guideline promulgators.
AB  - Medical practice guidelines are playing an increasingly important role in both
      the medical and the legal context. As tools for the health practitioner, it is
      thought that medical practice guidelines may contribute to an increase in the
      quality of patient care and cost-effectiveness. In the legal setting, guidelines
      may improve the functioning of the medical malpractice system by creating more
      rational, predictable standards of care. The development and promulgation of
      medical practice guidelines, while increasing, are still evolving. A number of
      concerns, especially in the areas of physician autonomy, physician control, and
      ethics, as well as efficacy, need to be resolved. The use of such guidelines as
      the legal standard of care in malpractice cases evokes similar concerns, along
      with fears that the use of guidelines at trial may either lower the standard of
      care, or, conversely, raise the standard of care to levels that are difficult to
      meet. Adding to this controversy is the recent case of Snyder v. American
      Association of Blood Banks (1996), in which the New Jersey Supreme Court upheld a
      jury finding that the American Association of Blood Banks (AABB) was liable to a
      plaintiff who contracted AIDS from an HIV-tainted transfusion, for negligent
      failure to adopt guidelines requiring blood testing for surrogate markers. This
      opinion is significant as the first to find a duty of care running from a medical
      guideline promulgator to a third person, the injured patient. The opinion is
      examined in depth and within the context of other relevant case law. The impact
      the opinion will have is difficult to gauge. The somewhat unique facts of the
      case, as well as the court's unusually stinging critique of the defendant, AABB,
      and its motivations informing its response to the concerns about blood
      contamination, may limit its value as precedent. However, precedent does exist in
      analogous non-medical cases for promulgator liability. The pros and cons of
      promulgator liability are weighed. While closer regulation of guideline
      development and promulgation or promulgator immunity may be warranted, it is
      premature to consider either seriously until the impact of the Snyder opinion can
      be appreciated.

PMID- 9524913
TI  - In the queue for total joint replacement: patients' perspectives on waiting
      times. Ontario Hip and Knee Replacement Project Team.
AB  - We assessed patients on the waiting lists of a purposive sample of orthopaedic
      surgeons in Ontario, Canada, to determine patients' attitudes towards time
      waiting for hip or knee replacement. We focused on 148 patients who did not have
      a definite operative date, obtaining complete information on 124 (84%). Symptom
      severity was assessed with the Western Ontario/McMaster Osteoarthritis Index and
      a disease-specific standard gamble was used to elicit patients' overall utility
      for their arthritic state. Next, in a trade-off task, patients considered a
      hypothetical choice between a 1-month wait for a surgeon who could provide a 2%
      risk of post-operative mortality, or a 6-month wait for joint replacement with a
      1% risk of post-operative mortality. Waiting times were then shifted
      systematically until the patient abandoned his/her initial choice, generating a
      conditional maximal acceptable wait time. Patients were divided in their
      attitudes, with 57% initially choosing a 6-month wait with a 1% mortality risk.
      The overall distribution of conditional maximum acceptable wait time scores
      ranged from 1 to 26 months, with a median of 7 months. Utility values were
      independently but weakly associated with patients' tolerance of waiting times
      (adjusted R-square = 0.059, P = 0.004). After splitting the sample along the
      median into subgroups with a relatively 'low' and 'high' tolerance for waiting,
      the subgroup with the apparently lower tolerance for waiting reported lower
      utility scores (z = 2.951; P = 0.004) and shorter times since their surgeon first
      advised them of the need for surgery (z = 3.014; P = 0.003). These results
      suggest that, in the establishment and monitoring of a queue management system
      for quality-of-life-enhancing surgery, patients' own perceptions of their overall
      symptomatic burden and ability to tolerate delayed relief should be considered
      along with information derived from clinical judgements and pre-weighted health
      status instruments.

PMID- 9524914
TI  - The use of clinical audit in evaluating maternity services reform: a critical
      reflection.
AB  - The clinical evaluation described here, using a casenote study, was part of a
      larger study evaluating the changes made to part of the maternity services in one
      NHS Trust, in response to the recommendations of Changing Childbirth (Department
      of Health 1993a). Results of the audit showed no evidence of a lowering of
      clinical standards within the study group and provided reassurance that a radical
      change in the model of care, with greatly enhanced continuity of career, an
      emphasis on community-based and midwifery-led care, and some reductions in labour
      interventions, could be implemented without compromising safety of care. The
      audit process raised a number of methodological problems which will need to be
      addressed in developing audit approaches which are able to reflect quality of
      care. It is important to recognize that the record of care is not a direct mirror
      of the care provided but a secondary source, kept for different purposes and
      designed to cover a different set of priorities from those which audit may seek
      to capture. The audit approach used in this study will be modified in continuing
      evaluation of the service as it moves from a pilot stage towards providing a
      mainstream service. Additional methods, including direct observation of care,
      will be employed in a sample of cases in order to assist in interpretation of
      audit findings.

PMID- 9524916
TI  - Essentialism, social constructionism, and the history of homosexuality.
AB  - Social constructionism is the view that homosexuality is not an atemporal and
      acultural phenomenon. Rather, homosexuality exists only within certain cultures
      and within certain time periods, most obviously Europe and North America after
      the nineteenth century. Essentialism is the view that homosexuality is an
      essential feature of human beings and that it could be found, in principle at
      least, in any culture and in any time. In this paper, I argue that the historical
      evidence available to us does not show that social constructionism is the correct
      view, and that essentialism is fully compatible with such evidence. Furthermore,
      I argue that the historical evidence does not even render social constructionism
      more probable than essentialism, i.e., both views are equally probable in the
      face of this evidence.

PMID- 9524915
TI  - "As long as they don't make an issue of it ...": gay men and lesbians in
      organized sports in The Netherlands.
AB  - At the request of the Dutch government, a group of researchers looked into the
      experiences of gay men and lesbians in organized, nonprofessional sports. The
      principal finding was that gay men and lesbians do not experience much
      discrimination. This circumstance results from the invisibility and silencing of
      homosexuality in athletics, both by sports organizations and by gay men and
      lesbians themselves. But in those sports where lesbians have become open about
      their sexuality, especially in soccer, they do encounter a high level of
      discrimination. Gay men, on the other hand, have not become visible in any sport.
      Several suggestions are offered on how to open up sports for lesbians and gay
      men.

PMID- 9524917
TI  - Secrecy, disclosure, and closet dynamics.
AB  - This paper examines the assumption that male homosexuality has a natural affinity
      with femininity and that male heterosexuality has a natural affinity with
      masculinity. An analysis of the relationship between people's disclosure or
      concealment of their homosexual practice or identity, particularly as it relates
      to notions of hegemonic masculinity and femininity provides the focus of this
      paper. It is argued that everyday understandings of homosexuality tend to be
      resolved in such as way as to press homosexuality into the service of privileging
      a male, masculine, and heterosexual subjectivity. This privileging is achieved,
      in part, as a result of the everyday social practices of homosexually active
      men's witting and unwitting deference to the hegemonic presumption that masculine
      men are naturally heterosexual, and its inverse, that feminine men are homosexual
      and are a perturbation of the natural order. We argue that this correlation is
      manufactured in everyday life in the world of appearances, but that the
      appearance of things is not reflected at a level of practice, which is to say,
      male homosexual practice is not necessarily feminine, just as male heterosexual
      practice is not necessarily masculine. Realities that conflict with the hegemonic
      realities are masked in the public world, for a variety of reasons. What we have
      called closet dynamics are the various discourses through which homosexuality is
      concealed and disclosed, and the various subject positions people take up in
      relation to those discourses.

PMID- 9524918
TI  - AIDS discourse: a critical reading of mainstream press surveillance of marginal
      identity.
AB  - This article examines the discursive strategies used by two major daily
      newspapers from the South from 1981 to 1994 as they construct the story of AIDS
      and represent gay identity and desire to the "general public." The research
      employs a cultural studies approach to communication to analyze power
      relationships at work in the discourse of these media texts. The research here
      makes use of and extends a previous study on the highly conservative Oklahoma
      City newspaper, The Daily Oklahoman, by comparing the findings to coverage in the
      more liberal Alabama daily, The Birmingham News. These were chosen because they
      offer examples of broadly circulated regional media and because they seemingly
      espouse opposing political orientations. Although the political positions of the
      two papers appear to be quite different, both papers marginalize and keep under
      surveillance gay identities, desire, and sexualities through coverage of AIDS;
      moreover, the press in both cases represents AIDS and gay identity in such
      excessive ways that marginalization and surveillance strategies are made to seem
      like a rational response to AIDS and gay desire. Finally, a cultural studies
      approach to media allows for an explanation of the recent media silence about
      AIDS and gay identity.

PMID- 9524919
TI  - Homophobia within schools: challenging the culturally sanctioned dismissal of gay
      students and colleagues.
AB  - In this paper we chronicle the prevalence of and cultural prescription for
      homophobia in the United States. The endemic nature of homophobia as it has been
      studied by behavioral scientists is reviewed. We then suggest that as social
      institutions reflecting cultural values, schools, colleges, and universities
      sanction an environment that neglects the value of gay students, staff, and
      faculty. Institutional homophobia dismisses the legitimacy of these individuals,
      thereby minimizing their contributions to learning. Addressed specifically are
      suggestions for training individuals who work with students to recognize,
      address, and challenge homophobia. We conclude that while the weight of American
      culture sanctions homophobia, training educators and personnel about the nuances
      of institutional homophobia may provide a fairer environment for gay students and
      colleagues. An appendix of resources describing effective programs for
      educational and training use is provided.

PMID- 9524920
TI  - Self-esteem and supportiveness as predictors of emotional distress in gay male
      and lesbian youth.
AB  - Many gay male and lesbian youth experience isolation, self-hatred, and other
      emotional stressors related to harassment and abuse from peers and adults,
      leading to risk factors associated with alcohol and substance abuse, suicide,
      prostitution, running away, and school problems. Research findings have indicated
      that high levels of self-esteem and social supports may moderate gay-identified
      stressors. The current study examined self-esteem and satisfaction with
      supportiveness as predictors of emotional distress in a sample of 90 self
      identified urban gay male and lesbian youth.

PMID- 9524921
TI  - Coming out for lesbian women: its relation to anxiety, positive affectivity, self
      esteem, and social support.
AB  - The present study investigated relations between lesbians' disclosure of their
      sexual orientation and psychological adjustment. The 499 participants responded
      to a questionnaire assessing level of self-disclosure, sources of social support,
      forms of socializing, self-description of sexual orientation, and length of self
      identification as a lesbian. The more widely a woman disclosed her sexual
      orientation the less anxiety, more positive affectivity, and greater self-esteem
      she reported. Degree of disclosure to family, gay and lesbian friends, straight
      friends, and co-workers was related to overall level of social support, with
      those who more widely disclosed reporting greater levels of support. Participants
      who more widely disclosed their sexual orientation were less likely to engage in
      anonymous socializing, had a larger percentage of lesbian friends, and were more
      involved in the gay and lesbian community. Path analyses revealed a mediating
      effect of social reactions (both initial and current) on the relation between
      identity development and self-disclosure.

PMID- 9524922
TI  - "Semi-straight sort of sex": class and gay community attachment explored within a
      framework of older homosexually active men.
AB  - Gay Community Attachment has proved a significant predictor of successful
      behavior change among gay-identifying men in response to HIV/AIDS. Related work
      at Macquarie University, Sydney, Australia, indicated that attachment to gay
      community is not a simple issue; rather, complex issues of sexual identity
      formation, the constraints of social inequality and localized sexual cultures
      inhibit the process of attachment and, therefore, successful HIV prevention. This
      paper discusses some of the findings from close-focus (qualitative) research on
      older homosexually active men which explore in depth the dynamic whereby these
      men attached themselves to gay community in terms of an analysis of class,
      generation, and the interplay with self-construction and masculinity.

PMID- 9524923
TI  - Erythropoietin stimulates nuclear localization of diacylglycerol and protein
      kinase C beta II in B6SUt.EP cells.
AB  - Erythropoietin (EPO) is a hormone, as well as a hematopoietic growth factor, that
      specifically regulates the proliferation and differentiation of erythroid
      progenitor cells. Although the membrane-bound receptor for EPO has no intrinsic
      kinase activity, it triggers the activation of protein kinases via phospholipases
      A2, C, and D. A cascade of serine and threonine kinases, including Raf-1, MAP
      kinase and protein kinase C (PKC) is activated following tyrosine
      phosphorylation. In this study, we have examined whether changes in nuclear PKC
      and 1,2-diacylglycerol (DAG) are induced following EPO treatment of the murine
      target cell line, B6SUt.EP. Western blot analysis using isoform-specific
      antibodies demonstrated the presence of PKC beta II, but not PKC alpha, beta I,
      gamma, epsilon, delta, eta, or zeta in the nuclei of cells stimulated with EPO.
      The increase in nuclear beta II levels was accompanied by an immediate rise in
      DAG mass levels with both of the increases peaking by 1 min. These rapid
      increases in nuclear DAG and PKC beta II expression suggest a mechanism for EPO
      induced changes in gene expression necessary for cell proliferation.

PMID- 9524924
TI  - The acute increases in vasomotor tone and blood pressure induced by carotid
      artery occlusion are modulated by platelet-activating factor (PAF) independently
      of nitric oxide release.
AB  - The purpose of the present study was to investigate the involvement of nitric
      oxide (NO) in the modulatory role of platelet-activating factor (PAF, 1-O
      hexadecyl-2-acetyl-sn-glyceryl-3-phosphorylcholine), a vasoactive phospholipid
      mediator synthesized by endothelial cells, on the vascular tone and arterial
      blood pressure. In pentobarbitone-anaesthetized rabbits, unloading of the carotid
      sinus baroreceptors by a bilateral carotid artery occlusion elicited a reflex
      rise in systemic vascular resistance, which was markedly potentiated by
      pretreating the animals with the PAF receptor antagonist WEB 2086 ([3-4-(2
      chlorphenyl-)-9-methyl-6H-thieno-3,2-f-1,2,4-triazolo-4,3 -alpha-1,4 -diazepin-2
      yl-(4-morpholinyl)-1-propanone]; 5 mg/kg, i.v.). In contrast, the inhibition of
      the biosynthesis of NO via NO synthase using N omega-nitro-L-arginine methyl
      ester (L-NAME) neither affected the systemic vasoconstriction induced by carotid
      artery occlusion nor modified the potentiating effect of WEB 2086. The
      haemodynamic alterations induced by L-NAME administration were corrected by
      continuous infusions of the directly-acting vasodilators sodium nitroprusside or
      diazoxide. The results of the present study confirm previous studies from our
      group suggesting the involvement of PAF in a negative feedback mechanism
      effective in the local regulation of vasomotor tone in anaesthetized rabbits, but
      exclude the participation of NO in this process.

PMID- 9524925
TI  - Mechanism of arachidonic acid-induced Ca2+ mobilization in liver nuclei.
AB  - Arachidonic acid treatment in isolated liver nuclei resulted in a rapid and
      transient increase of Ca2+ concentration in the nucleoplasm which was monitored
      with the Ca(2+)-sensitive dye fura-2 dextran. This effect was associated with a
      decrease of Ca2+ concentration in the nuclear envelope as measured with fura-2
      AM. Our results indicate that arachidonic acid causes a Ca2+ release from the
      nuclear envelope to the nucleoplasm similar to that evoked by inositol
      trisphosphate (IP3). The arachidonic acid-induced Ca2+ mobilization in the
      nucleus was not due to the metabolites of arachidonic acid. Experiments performed
      in the presence of ATP and Ca2+ indicate that arachidonic acid-induced Ca2+
      mobilization in the nucleus takes place in a non ATP-dependent way. Taken
      together, these results suggest that arachidonic acid may contribute to the
      regulation of nuclear Ca2+ mobilization.

PMID- 9524926
TI  - Activation of PKC, superoxide anion production and LDL lipid peroxidation are not
      dependent on phosphoinositide-specific phospholipase C activity in U937 cells.
AB  - Our previous studies have shown that both increase in Ca2+ levels and activation
      of protein kinase C (PKC) are required for monocyte-mediated O2- production and
      low density lipoprotein (LDL) peroxidation. Phosphoinositide-specific
      phospholipase C (phosphoinositidase C or PIC) is believed to mediate release of
      intracellular Ca2+ through InsP3 formation and activation of PKC through
      diacylglycerol (DAG). In these studies, we investigated the PIC pathway for its
      participation in monocytic cell-mediated lipid peroxidation of LDL. We found
      substantial InsP3 formation in opsonized zymosan (ZOP)-activated U937-b cells,
      indicating the activation of PIC. Both inhibition of PIC by the PIC inhibitor U
      73122 and reduction of the supply of the precursor lipid by lithium chloride
      suppressed InsP3 formation but did not alter LDL lipid peroxidation nor O2-
      production by activated cells. Furthermore, we also found that suppression of PIC
      activity had no substantial inhibitory effect on PKC activity in ZOP-activated
      human monocytes. Our data suggest that PIC activity is induced upon cell
      activation resulting in increased levels of InsP3. The activity of this pathway,
      however, is not required for cell-mediated O2- production, PKC activation or LDL
      oxidation.

PMID- 9524927
TI  - Characterization and representative structures of N-oligosaccharides bound to
      apolipoprotein H.
AB  - We studied the structure of N-linked carbohydrates bound to apolipoprotein H by a
      combination of two methods which make use of lectins. Digoxigenin-labelled
      lectins are used for the structural characterization of carbohydrate chains of
      glycoproteins. Concanavalin A lectin affinity chromatography was used to analyse
      apolipoprotein H according to the characteristics of its carbohydrate chain inner
      to sialic acid residues. Our results from digoxigenin-labelled lectins analysis
      showed that apolipoprotein H gave positive bands to SNA, DSA, GNA, PNA and AAA
      lectins. Apolipoprotein H gave a negative band when reacted with MAA lectin. When
      we applied apolipoprotein H onto the Concanavalin A lectin column no detectable
      amounts of protein were eluted with Concanavalin A buffer. After adding a buffer
      with low sugar concentration (10 mM glucoside) a large amount of apolipoprotein H
      was recovered. These molecules of apolipoprotein H weakly bound to the lectin.
      When a higher sugar concentration (500 mM mannoside) was added most of the sample
      applied was eluted. These molecules of apolipoprotein H firmly bound to the
      column having high affinity for the lectin. These results combined with those
      coming from the digoxigen-labeled lectins method enable us to understand the
      inner structure of carbohydrate chains with their outer branches. Molecules of
      apolipoprotein H which weakly bind to Concanavalin A could bear complex N-glycans
      organized in biantennary or truncated hybrid structures. Firmly bound
      apolipoprotein H referred to molecules rich in N-glycan hybrid structures. They
      have an outer branch belonging to the high mannose carbohydrate chains which
      explain the ability to bind to the column and an other main branch bearing the
      sequence galactose beta-(1-4)-N-acetylglucosamine beta-(1-2) mannose. Galactose
      could be the terminal sugar or, alternatively, be masked with sialic acid alpha
      (2-6) terminally linked.

PMID- 9524928
TI  - Possible mechanisms for the differential effects of high linoleate safflower oil
      and high alpha-linolenate perilla oil diets on platelet-activating factor
      production by rat polymorphonuclear leukocytes.
AB  - As compared with high dietary linoleate safflower oil, high dietary alpha
      linolenate perilla oil decreased platelet-activating factor (PAF) production by
      nearly half in calcium ionophore (CaI)-stimulated rat polymorphonuclear
      leukocytes (PMN). In the CaI-stimulated PMN from the perilla oil group, the
      accumulated amount of arachidonate (AA) plus eicosapentaenoate (EPA) was 30% less
      and that of lyso-PAF was 50% less, indicating that the decreased availability of
      lyso-PAF is a factor contributing to the relatively low PAF production.
      Consistently, eicosatetraynoic acid (ETYA), a dual inhibitor of cyclooxygenase
      and lipoxygenase, increased free fatty acids (FFA) and decreased PAF production
      possibly by decreasing the availability of lyso-PAF. Although, leukotrienes (LTs)
      have been proposed to stimulate PAF production synergistically, a potent LTB4
      receptor antagonist, ONO-4057, decreased the formation of free fatty acids and
      LTB4, but stimulated PAF production somewhat, indicating that LTB4 may not
      stimulate PAF production in PMN. Lysophospholipid-induced transacylase (CoA
      independent transacylase) activity in PMN homogenates was 25-30% lower in the
      perilla oil group but no significant differences were observed in the lyso-PAF
      acetyltransferase and PAF acetylhydrolase activities between the two dietary
      groups. Thus, decreased transacylase activity is another factor associated with
      the relatively low PAF production in the perilla oil group.

PMID- 9524929
TI  - Checking the projection display of multivariate data with colored graphs.
AB  - Projection methods such as principal component analysis (PCA), nonlinear mapping
      (NLM), and the self-organizing map (SOM) are valuable algorithms for visualizing
      multidimensional data in a two-dimensional plane. Unfortunately, the reduction of
      the dimensionality involves distortions. In an attempt to graphically localize
      the distortions of the projected data, we suggest superposing colored graphs onto
      the 2D plots. The color of the edges of these graphs encodes the original high
      dimensional distances between the connected points. The method is applied to a
      cluster analysis of 37 biologically active compounds and 471 molecules
      represented by a structural 3D descriptor.

PMID- 9524930
TI  - Computer simulation study on the conversion of spirolactone to enones over H-Y
      zeolite.
AB  - We report here the results of computer modeling studies and quantum chemical
      calculations on the spirolactone-to-enone conversion reaction over the zeolite
      catalysts, especially H-Y zeolite. We studied the adsorption mode of the
      molecules inside the supercage of H-Y and the mechanism of electron transfer
      between organic molecules and the framework of zeolite H-Y by density functional
      theory (DFT) calculations. Because the organic molecules considered in the
      present study are less symmetrical we docked the molecule inside the supercage of
      H-Y and energy minimization was then applied to these docked structures to yield
      representative low-energy binding sites for the molecules within the host
      structure. The interaction energy results show that the major interaction is
      between the methylene hydrogen of the molecule and the oxygen of the framework.
      The molecular electrostatic potential maps show that the ketonic oxygen of the
      reactant molecules abstract proton from Bronsted acid site. Thus the mechanism
      proposed by DFT calculation matches well with the experimental observations.

PMID- 9524931
TI  - Using a genetic algorithm to identify common structural features in sets of
      ligands.
AB  - This article describes a program for pharmacophore mapping, called MPHIL (Mapping
      Pharmacophores in Ligands). Given as input a set of molecules that exhibit some
      common biological activity, MPHIL identifies the smallest 3D pattern of
      pharmacophore points that has at least m (a user-defined parameter) points in
      common with each of the input molecules. The program thus differs from existing
      programs for pharmacophore mapping in that it does not require all of the
      molecules to share exactly the same pattern of points, although it will find such
      a common pattern if it does, indeed, exist. MPHIL uses a genetic algorithm (GA)
      approach in which an initial, and very rapid, GA is used to suggest possible
      combinations of points that are then processed by the second GA to yield the
      final 3D pattern.

PMID- 9524932
TI  - A further implementation of the rotational symmetry boundary conditions for
      calculations of P4(3)2(1)2 symmetry crystals.
AB  - One of the most accurate styles of protein simulation is to calculate proteins in
      crystalline environment without neglect of long-range interactions. The long
      range interactions can be accelerated by various methods. However, as a unit cell
      of a protein crystal is a large molecular assembly, its simulation is still
      unpractical without high-speed computers. Thus this article is addressed to the
      reduction of calculational volumes for protein crystal simulation by a further
      implementation of the rotational symmetry boundary condition method. For protein
      crystals in P4(3)2(1)2 symmetry, a computational cell and related tables were
      developed. A 120-ps molecular dynamics simulation was performed for a P4(3)2(1)2
      symmetry crystal of glycogen phosphorylase b under rotational symmetry boundary
      conditions. The computational cell was one-eighth of the unit cell in volume, and
      less than about one-fourth of the conventional periodic boundary box. Generation
      of neighbor atom pair lists was greatly accelerated, and thus the simulation was
      practical even with a personal computer.

PMID- 9524933
TI  - SERF: a program for accessible surface area calculations.
AB  - The program SERF has been designed to facilitate the greater use of accessible
      surface area calculations in the analysis of protein structure, including
      analysis of surface area changes on binding and complexation. For comparative
      purposes, the program implements a number of alternative methods for calculating
      surface areas, including those that approximate residues by single spheres.
      Algorithmic details, comparative performance, and the software implementation of
      SERF are discussed.

PMID- 9524934
TI  - Clique-detection algorithms for matching three-dimensional molecular structures.
AB  - The representation of chemical and biological molecules by means of graphs
      permits the use of a maximum common subgraph (MCS) isomorphism algorithm to
      identify the structural relationships existing between pairs of such molecular
      graphs. Clique detection provides an efficient way of implementing MCS detection,
      and this article reports a comparison of several different clique-detection
      algorithms when used for this purpose. Experiments with both small molecules and
      proteins demonstrate that the most efficient of these particular applications,
      which typically involve correspondence graphs with low edge densities, is the
      algorithm described by Carraghan and Pardalos. This is shown to be two to three
      times faster than the Bron-Kerbosch algorithm that has been used previously for
      MCS applications in chemistry and biology. However, the latter algorithm enables
      all substructures common to a pair of molecules to be identified, and not just
      the largest ones, as with the other algorithms considered here. The two
      algorithms can usefully be combined to increase the efficiency of database
      searching systems that use the MCS as a measure of structural similarity.

PMID- 9524935
TI  - Isolation of serotype 2 Marek's disease virus from a cell line of avian lymphoid
      leukosis.
AB  - To determine a serotype of Marek's disease virus (MDV) persistently infected in a
      lymphoid leukosis (LL)-cell line, LSCC-BK3, clone A (BK3A), and to examine the
      pathogenicity of the virus, an attempt was made to isolate MDV from culture fluid
      of the LL-cell line, using chick embryo fibroblast cultures resistant to
      infection with subgroup A avian leukosis virus (ALV) to eliminate subgroup A ALV.
      The MDV isolate, serologically identified as serotype 2 MDV and designated as the
      2H strain, was free from ALV and reticuloendotheliosis virus. A serotype 2
      specific antigen of MDV was detected in 44% of BK3A, but antigens of serotypes 1
      and 3 were not detected in this cell line, by the indirect immunofluorescent
      antibody test using serotype-specific monoclonal antibodies. MDV antigens were
      undetectable in LSCC-BK3, clone 2C; both cell lines were established from the
      same chicken. Neither clinical signs nor macroscopic lesions were observed in any
      of 19 chicks inoculated with the 2H strain. Three out of 19 chicks
      histopathologically examined had no lesions. These results suggest that serotype
      2 MDV can persist in B cells transformed by ALV without cytopathic effect at a
      high rate, and the isolate may become a candidate for MD vaccine strains.

PMID- 9524936
TI  - Effects of fighting after grouping on plasma cortisol concentration and
      lymphocyte blastogenesis of peripheral blood mononuclear cells induced by
      mitogens in piglets.
AB  - One litter (Group A) of three unacquainted groups of littermates (4
      piglets/litter), 64.0 +/- 0.8 days old, was moved to the pen of another litter
      (Group B) and they were housed together for 19 days after grouping (phase 1). The
      pigs in Group B violently attacked all the pigs in Group A for 9 hr after
      grouping. The remaining group was not grouped and used as controls. The plasma
      cortisol concentrations 1 hr after grouping were significantly higher than those
      1 hr before and 24 hr after grouping, and the suppression of lymphocyte
      blastogenesis of peripheral blood mononuclear cells (PBMC) induced by mitogens
      was observed on 3, 8 and 19 days after grouping. After phase 1 ended, the pigs in
      Group A were returned to their own pen for 7 days, and then they were regrouped
      with the pigs in Group B and reared together for a further 14 days. Neither
      agonistic behavior nor change of plasma cortisol after regrouping was seen.
      Though the lymphocyte blastogenesis of PBMC induced by the mitogens on day 0
      after regrouping was significantly lower in the pigs of Groups A and B compared
      to those in control pigs, a significant difference in lymphocyte blastogenesis
      among three groups was not seen on 7 and 14 days after regrouping. These findings
      indicate that fighting after grouping unacquainted litters increases plasma
      cortisol, and suppresses lymphocyte blastogenesis for 26 days after grouping.

PMID- 9524937
TI  - Production of a monoclonal antibody reacted broadly with feline calicivirus field
      isolates.
AB  - A monoclonal antibody (MAb) reactive with 36 field isolates and 2 laboratory
      strains of feline calicivirus (FCV) was produced by immunizing mice with the
      mixture of FCVs. The MAb (4D7) reacted with FCVs in an enzyme-linked
      immunosorbent assay (ELISA), but had no neutralizing activity against the F4
      strain of FCV. MAb 8G1, previously produced against the FCV F4 strain, also
      reacted in ELISA with all FCVs used in the present study. However, the epitopes
      recognized by 4D7 and 8G1 were different. Using these two MAbs and a polyclonal
      rabbit antibody, we attempted to develop a sandwich ELISA for detection of FCV
      antigen. The combination of 4D7 and the polyclonal rabbit IgG was most sensitive.
      Using this system, all the field isolates of FCV cultured in vitro were detected.
      However, among the 36 swab samples, from which FCV was isolated, 4 were negative.

PMID- 9524938
TI  - Morphology and morphometry of skulls of raccoon dogs, Nyctereutes procyonoides
      and badgers, Meles meles.
AB  - In order to obtain the basic data to identify the skeletal remains from the
      archaeological sites, morphological and morphometrical studies were carried out
      on skulls of living raccoon dogs (35 males and 45 females) and badgers (16 males
      and 8 females) from Kagoshima Prefecture. Macroscopically, the sexual differences
      were observed in badgers for the parts of the zygomatic process of the temporal
      bone and the occipital squama, but were not in raccoon dogs. Among 24 cranial
      measurements, significant sexual differences were found in five measurement items
      in raccoon dogs, while 12 items in badgers. Mandibles showed significant sexual
      differences in both species. Raccoon dogs had significantly larger values than
      badgers in most of the items concerning length of cranium and most mandibular
      measurements. The discrimination efficiencies of discriminant formulae between
      both sexes were lower in raccoon dogs, but higher in badgers, and the
      efficiencies between both species were obtained 100%. In the regression formulae
      for estimating skull length, some formulae showed high coefficients of
      determination in both species. These observations represented interspecific and
      sexual differences in the skulls of raccoon dogs and badgers.

PMID- 9524939
TI  - Effect of ozone treatment on Toxocara canis eggs.
AB  - The effect of ozone treatment on the development and viability of Toxocara canis
      eggs was studied. Despite treatment with ozone, unembryonated T. canis eggs could
      develop into viable second-stage larvae when assayed by larvae recovery after
      oral inoculation into mice. The viability of second stage larvae of T. canis was
      also not affected by ozone treatment. No significant difference was observed in
      the larvae recovery count and migratory pattern of the ozone-treated larvae and
      the untreated control because the majority of the larvae were recovered from the
      liver and lungs on day 2 postinoculation. However, scanning electron microscopy
      of the ozone treated T. canis eggs showed many blebs on the surface of the
      protein coat at the basement of the honeycomb-like structures. The honeycomb-like
      structures on the egg surface were also observed to be distorted after ozone
      treatment. Thus, in spite of inducing some surface morphological changes on the
      egg, ozone was observed to have no effect on the viability of the embryonated
      second stage larvae of T. canis.

PMID- 9524940
TI  - Development of an enzyme-linked immunosorbent assay using recombinant chicken
      anemia virus proteins expressed in a baculovirus vector system.
AB  - Recombinant baculoviruses were constructed to express the putative proteins VP1,
      VP2 or VP3 of the chicken anemia virus (CAV). The recombinant VP1, VP2 or VP3
      were detected by SDS-PAGE, and their molecular weights were 50, 30/27 and 16 kDa,
      respectively. The VP2 and VP3 reacted with sera from CAV-infected chickens in
      Western blot analysis and when used as an enzyme-linked immunosorbent assay
      (ELISA) antigen, but VP1 did not. Antibodies to CAV were detected, by ELISA using
      crude insect cell lysates containing VP2 or VP3, from 2 to 20 weeks or 2 to 7
      weeks after CAV infection, respectively. These findings indicate that recombinant
      VP2 and VP3 expressed in the baculovirus vector system can be used as antigens to
      detect anti-CAV antibodies in ELISA.

PMID- 9524941
TI  - The presence of two low molecular mass proteins immunologically related to 14
      kilodalton serum amyloid A in the lipoprotein fraction and their decreased serum
      concentrations in calves with experimentally induced pneumonia.
AB  - A 14 kilodalton (kDa) serum amyloid A (apoSAA) protein was purified from cow
      serum. Rabbit antiserum to the 14 kDa apoSAA recognized, in addition to the 14
      kDa protein, a 7.5-9.0 kDa protein and a protein having a molecular mass of less
      than 6.5 kDa (< 6.5 kDa protein). The possibility that the two proteins were
      contaminants was excluded by results showing that the two proteins detected in
      early stages of purification procedures were not found in the purified 14 kDa
      apoSAA fraction, as revealed by immunoblot analysis. As in the 14 kDa apoSAA, the
      7.5-9.0 kDa protein was localized in the high-density lipoprotein fraction, while
      the < 6.5 kDa protein was in the low-density lipoprotein fraction. In calves with
      pneumonia induced by inoculation to the lungs of Pasteurella haemolitica, the
      serum concentration of the 14 kDa apoSAA was increased, whereas those of the 7.5
      9.0 kDa and the < 6.5 kDa proteins were conversely decreased. The time-course
      study indicated that the increase in concentration of the 14 kDa apoSAA and
      decrease in that of the < 6.5 kDa protein occurred almost simultaneously. These
      results suggest that the 14 kDa apoSAA and the immunologically related 7.5-9.0
      kDa and < 6.5 kDa proteins act as positive and negative acute phase reactants,
      respectively, and also that concentrations of the three proteins are regulated in
      concert in acute phase plasma.

PMID- 9524942
TI  - Distribution of lectin binding in spermatogonia of Syrian hamsters in gonadally
      active and inactive states.
AB  - Lectin binding patterns in spermatogonia of Syrian hamsters in gonadally active
      and inactive states were examined by light and electron microscopy. After
      exposure to a short day cycle (SD), the testis weight and the diameter of
      seminiferous tubules decreased, reaching the minimum at 13 weeks. At that time,
      spermatogenesis was severely disrupted. In the animals kept exposed to an SD,
      spermatogenesis reinitiated spontaneously after 23 weeks. In the animals
      transferred to a long day cycle (LD) after exposure to an SD for 13 weeks,
      spermatogenesis reinitiated only 4 weeks later. As to the lectin binding,
      Dolichos biflorus agglutinin (DBA) bound specifically to spermatogonia. The
      number of DBA-positive spermatogonia per one seminiferous tubule increased until
      13 weeks after exposure to an SD, and then gradually decreased. DBA bound to only
      type A spermatogonia in active testes, whereas it bound to type A, intermediate
      and type B spermatogonia in inactive testes. Moreover, SDS-PAGE and Western blot
      analysis of testes in active and inactive states indicated that DBA-binding bands
      (115 kDa, 76 kDa) in inactive testes were intense compared with those in active
      testes. The 82 kDa band was detected only in inactive testes. These results
      supported the finding obtained from lectin histochemistry. DBA-binding
      glycoprotein was detected in all types of spermatogonia in inactive testes,
      suggesting that this glycoprotein way concern the active/inactive state of
      spermatogenesis. The present study also indicated that DBA is a useful marker for
      spermatogonia in inactive testes of Syrian hamster.

PMID- 9524943
TI  - Induction of dog sperm capacitation by oviductal fluid.
AB  - Four estrous beagles were inseminated with 1 x 10(8) sperm into both the right
      and left uterine horns, and the uterine horn and oviduct on one side were removed
      under anesthesia after 7 hr and 24 hr, respectively. The lumen of the uterine
      horns and oviducts was flushed with canine capacitation medium (CCM), and
      movement of the sperm in CCM was assessed by phase-contrast microscopy. In a
      second experiment, ejaculated sperm obtained from 5 normal beagles was incubated
      in CCM supplemented with oviductal flush fluid (OF-CCM) at 38 degrees C with 5%
      CO2 in air. Motility of sperm, and percentages of hyperactivated sperm (%HA) and
      acrosome-reacted sperm (%AR) among freely swimming (FS) sperm were investigated
      until 24 hr after the start of incubation. After 7 hr of incubation the sperm was
      coincubated with canine oocytes in OF-CCM for 2 hr, and the number of zona
      pellucida-binding (zona-binding) sperm was then counted. The %HA among the sperm
      in the oviductal flush fluid both 7 hr (mean +/- S.E.; 15.0 +/- 2.4%) and 24 hr
      (77.5 +/- 5.2%) after intrauterine insemination were significantly higher than in
      the uterine flush fluid (P < 0.05, 0.01, respectively). The motility and %HA
      among FS-sperm in OF-CCM were higher than in the control medium without oviductal
      fluid. However, there was no difference in the %AR between OF-CCM and control
      medium. The number of zona-binding sperm in OF-CCM (8 +/- 1) was significantly
      greater than in control medium (5 +/- 1) (P < 0.05). These results suggest that
      oviductal fluid in the estrous bitch maintains sperm motility and induces sperm
      capacitation.

PMID- 9524944
TI  - Purine metabolism of uric acid urolithiasis induced in newborn piglets.
AB  - To clarify the relationship between uric acid urolithiasis and purine catabolites
      in newborn piglets, the incidence of uric acid urolithiasis and the plasma
      concentrations of xanthine, hypoxanthine, uric acid and allantoin were examined
      in 32 piglets. The newborn piglets were divided into two groups: normal (over 1.2
      kg, n = 18, group N) and low body weight (below 0.9 kg, n = 14, group L). The
      animals in both groups were given water (non-nutrition, n = 11, treatment W),
      artificial milk (normal nutrition, n = 12, treatment M), or a combination of
      water and allopurinol (prophylactic treatment for the urolithiasis, n = 9,
      treatment A), during the first 60-hr of birth. At necropsy, the incidence of
      urolithiasis was higher in the piglets that received treatment W than those in
      the treatment M or A in both the N and L groups. In group L, the plasma xanthine,
      hypoxanthine and uric acid concentrations were markedly increased in the piglets
      that underwent treatment W compared with the treatment M. In both the N and L
      groups, the plasma allantoin concentration was higher in the treatment W piglets
      as compared with the treatment M piglets. These results suggested that the
      occurrence of uric acid urolithiasis in the newborn piglets is attributable to
      increased purine catabolites due to a starvational condition after birth.

PMID- 9524945
TI  - Higher sensitivity in induction of apoptosis in fibroblast cell lines derived
      from LEC strain rats to UV-irradiation.
AB  - The proportion of S-phase cells in a WKAH rat cell population decreased and that
      of G1-phase cells increased at 8 and 18 hr post-incubation following UV
      irradiation, although no significant change was observed in the ratio of the
      proportion of S-phase to G1-phase cells in a LEC rat cell population. Thus, UV
      radiation-induced delay in the progression from the G1 to S phase was observed in
      WKAH rat cells but was not apparent in LEC rat cells. The fraction of LEC rat
      cells containing a sub-G0 DNA content increased with post-incubation time after
      UV-irradiation, but not that of WKAH rat cells. The proportion of the sub-G0
      fraction in LEC rat cells increased with increasing doses of UV-rays. Low
      molecular weight DNAs extracted from UV-irradiated LEC rat cells exhibited an
      intense DNA ladder pattern at 18 and 24 hr post-irradiation by electrophoretic
      analysis, but not those from UV-irradiated WKAH rat cells. These results showed a
      higher sensitivity of LEC rat cells in induction of apoptosis than that of WKAH
      rat cells to UV-irradiation, although there was no difference in the survival
      curves among the cell lines from LEC and WKAH rats after UV-irradiation.

PMID- 9524946
TI  - Hemodynamic changes during administration of drugs for mitral regurgitation in
      dogs.
AB  - Each of 5 drugs, i.e., 4 different vasodilator drugs (captopril, enalapril,
      hydralazine and prazosin) and a cardiotonic drug (digoxin), was administered to
      dogs with mitral regurgitation (MR) for 1-72 days in order to quantitatively
      evaluate the influence of therapeutic agents on blood flow in heart disease.
      Hemodynamic changes were assessed before and after administration of each drug by
      determining mitral regurgitant jet mapping area (MRMA) and aortic forward flow
      mapping area (AFMA), which were displayed by the color Doppler method, and the
      ratio of MRMA to AFMA (MRMA/AFMA) as parameters. When the four vasodilator drugs
      were used appropriately, MRMA and MRMA/AFMA decreased in all cases, compared with
      the values before the administration. These two parameters showed dose-dependent
      changes after administration of captopril, enalapril and hydralazine. When the
      cardiotonic drug was used. MRMA and MRMA/AFMA increased in 4 of 5 cases. The
      MRMA/AFMA values were slightly more reproducible than the MRMA values, whereas
      the AFMA values showed no constant tendency when any vasodilator drug or the
      cardiotonic drug was used. These results suggest that the efficacy of cardiotonic
      and vasodilator drugs in MR can be quantitatively evaluated by determining
      MRMA/AFMA in particular, and MRMA.

PMID- 9524947
TI  - Nucleotide sequences of glycoprotein I and E genes of equine herpesvirus type 4.
AB  - The nucleotide sequences of the glycoprotein I (gI) and E (gE) genes of equine
      herpesvirus type 4 (EHV-4) strain TH20 were determined. The predicted region
      encoding the EHV-4 gI gene is 1,263 nucleotides, corresponding to a polypeptide
      of 420 amino acids in length. The predicted region encoding the EHV-4 gE gene is
      1,647 nucleotides, corresponding to a polypeptide of 548 amino acids in length.
      The EHV-4 gI and gE genes show 74% and 85% identity at the amino acid level with
      those of equine herpesvirus type 1 (EHV-1), respectively. Furthermore, we have
      found an open reading frame homologous to the EHV-1 gene 75, which overlaps in
      part with the 3' end of EHV-4 gE gene. These sequence data will be useful for
      development of a modified live vaccine against equine herpesvirus type 1 and 4
      infections.

PMID- 9524948
TI  - Retroviral sequence located in border region of short unique region and short
      terminal repeat of Md5 strain of Marek's disease virus type 1.
AB  - A 246-base pair (bp) retroviral sequence, which was homologous to a long terminal
      repeat of avian erythroblastosis virus (AEV), was detected and cloned from Md5
      strain (Md5) of Marek's disease virus type 1 (MDV1) by representational
      difference analysis (RDA). The retroviral sequence was thought to be located in
      the border region of short unique region (U(s) and short terminal repeat (TRs),
      but did not exist in the border region of U(s) and the inverted short repeat
      (IRs) of the Md5 genome. A cloned fragment of the US/TRs border region of the Md5
      genome showed a construction of U-E'-R-U'-E-TRs with the regions designated as
      follows: E, expanded TRs reported by Jones et al. [Proc. Natl. Acad. Sci. U.S.A.
      90, 3855, 1993]; E', a partial copy of the expanded TRs; R, the retroviral
      sequence detected in Md5 genome; U, TRs-end sequence of U(s); U', a partial copy
      of TRs-end sequence of U(s). The sequence unit indicated as E'-R-U' was thought
      to be heterogeneously repeated in the Md5 genome. Since this retroviral sequence
      reportedly did not exist in the original stock of Md5, the retroviral sequence is
      thought to be inserted in the Md5 genome without experimental co-infection of
      avian cells with retrovirus and MDV1. These results suggest that RDA could be
      useful for the detection of retroviral sequences in the herpesvirus genome.

PMID- 9524949
TI  - Analysis of immunodominant piroplasm surface protein genes of benign Theileria
      parasites distributed in China and Korea by allele-specific polymerase chain
      reaction.
AB  - Benign Theileria species distributed in China and Korea were characterized by
      allele-specific polymerase chain reaction (PCR), based on the sequences of major
      immunodominant piroplasm surface protein genes. In China, all the isolates
      contained Chitose (C) type parasites. One out of 5 isolates tested was a mixed
      population of Ikeda (I), C and B-2 types, whereas, all the isolates from Korea
      consisted of I type parasites. Except for 4 isolates, 29 isolates from Korea
      consisted of more than two types of parasites. The present data showed that
      benign Theileria species distributed in these countries were mixed parasite
      populations.

PMID- 9524951
TI  - Degradation of myocardiac myosin and creatine kinase in rats given alkaline
      ionized water.
AB  - Recently, the authors have shown that marked necrosis and fibrosis of myocardium
      were observed in rats given alkaline ionized water (AKW). To clarify the cause of
      myocardial lesions, the activities of myosin ATPase, actomyosin ATPase and
      creatine kinase (CK) in myocardium of rats given AKW at 15 weeks-old were
      compared with those in myocardium of rats given tap water (TPW). Furthermore,
      sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) of
      myocardiac myosin and isoelectric focusing (IEF) of myocardiac CK were performed
      which revealed a distinct difference between AKW and TPW groups. The activities
      of myosin ATPase and actomyosin ATPase in the AKW group were higher than those in
      the TPW group, and these elevated activities were caused by the degradation of
      myosin in the AKW group judging from the SDS-PAGE pattern of myosin. On the other
      hand, the activity of CK in the AKW group was lower than that in the TPW group,
      and the IEF pattern of CK showed leakage of myocardiac CK. These results indicate
      that increases in actomyosin ATPase activity and myosin ATPase activity, plus the
      decrease in CK activity caused the disorder of coupled reaction in male rats
      given AKW at 15 weeks-old. It is concluded that this disorder of coupled reaction
      may cause marked myocardiac necrosis and fibrosis in rats given AKW.

PMID- 9524950
TI  - Protective effect of lactoferricin against Toxoplasma gondii infection in mice.
AB  - The protective effect of lactoferricin against Toxoplasma gondii infection was
      examined in experimental murine toxoplasmosis. All mice orally administered 5.0
      mg of lactoferricin, and challenged with cysts of T. gondii at a dose of LD90
      survived until the end of experiment (35 days post challenge). Intraperitoneal
      administration of 0.1 mg of lactoferricin also prevented death in 100% of treated
      mice challenged with T. gondii cysts. In contrast, 80% of untreated mice died of
      acute toxoplasmosis within 14 days post challenge. In the mice treated perorally
      with lactoferricin, the number of cysts in the brain was significantly lower than
      that in untreated mice. Levels of interferon-r in the serum of infected mice
      treated perorally with lactoferricin showed a tendency to lower than those in the
      infected mice without treatment. These results demonstrate that oral
      administration of lactoferricin induces resistance to T. gondii infection in
      mice.

PMID- 9524952
TI  - Isolation of Coxiella burnetii from the vagina of feline clients at veterinary
      clinics.

PMID- 9524953
TI  - Survey of Theileria parasite infection in cattle in Taiwan.
AB  - An survey of Theileria parasite infection in cattle in Taiwan was carried out by
      polymerase chain reaction (PCR). A total of 491 blood samples, 105 from southern
      area and 386 from northern area, were collected from bovine in 16 different
      farms. From northern area, Theileria piroplasms could be seen in only 4 of 105
      blood samples microscopically. However, when p32/34 genes (encoding
      immunodominant piroplasm surface proteins) were amplified by PCR, 15 blood
      samples were detected positive. They were analyzed by using allele-specific
      primers of 3 allelic forms of p32/34 and all contained C type of T. sergenti.
      Four blood samples were found infected with both C and B (T. buffeli) type
      parasites. Examination of 386 blood samples from southern area of Taiwan did not
      reveal any Theileria parasite microscopically, as well as by PCR amplification.

PMID- 9524954
TI  - Changes of ovarian structures, plasma LH, FSH, progesterone and estradiol-17 beta
      in a cow with ovarian cysts showing spontaneous recovery and relapse.
AB  - In a cow diagnosed as having ovarian cysts, we observed changes in the ovarian
      structures by ultrasonography for 71 days and examined plasma concentrations of
      sex hormones. The cow had 2 regressing cysts at the start of this study and 3 new
      follicles subsequently developed into cysts. With regression of these cysts, 2
      new follicles developed and ovulated spontaneously, followed by the formation of
      2 corpora lutea. On the day prior to ovulation, a preovulatory luteinizing
      hormone (LH) surge was detected. With regression of the corpora lutea, a new
      follicle developed and underwent atresia. Meantime, another follicle developed
      and became a cyst without ovulation. No preovulatory LH surge was observed during
      the period from regression of the corpora lutea to cyst formation. The results
      indicate that absence of the preovulatory LH surge is associated with occurrence
      of ovarian cysts and this endocrine aberration is reversible.

PMID- 9524955
TI  - Survival of transfused CD18-positive granulocytes and their chemiluminescent
      response in a heifer with leukocyte adhesion deficiency.
AB  - Granulocyte transfusion (GT) was performed in an 8-month-old heifer with
      leukocyte adhesion deficiency (BLAD) to monitor the changes in transfused CD18
      positive neutrophils and associated neutrophil chemiluminescent (CL) response in
      beta 2-integrin-deficient host. The CD18-positive neutrophils were detected in
      blood from the BLAD heifer during the first 3 hr after 2.6 x 10(9) cells were
      infused by GT, and disappeared by 5 hr after GT. The CL response of neutrophils
      was increased 1.7 to 2.8-fold in the BLAD heifer during the first 3 hr after GT,
      thereafter CL response decreased gradually from 2 to 5 hr after GT.

PMID- 9524956
TI  - Persistent hyperplastic primary vitreous (PHPV) in two Siberian husky dogs.
AB  - Three eyes in two Siberian husky dogs were clinically diagnosed as persistent
      hyperplastic primary vitreous (PHPV) by means of ophthalmoscopy and
      ultrasonography (USG). Examination of mildly affected PHPV eyes with an
      ophthalmoscope showed the axial part of the posterior capsule to be opaque. The
      central lesion of the posterior capsule in severely affected eyes had been opaque
      with many blood vessels. Echographic changes in mild cases of PHPV were outside
      of the lens, linearly hyperechoic, parallel to the posterior lens capsule. In a
      severely affected eyeball, funnel-shaped hyperechoic change was noted in the
      retrolental space. Two months later, phacoemulsification was performed for
      diagnostic treatment of PHPV since progressive cataract was observed in this eye.

PMID- 9524957
TI  - Antigenic characteristic of the lipopolysaccharides of Coxiella burnetii
      isolates.
AB  - Lipopolysaccharides (LPSs) of 8 isolates of Coxiella burnetii from a variety of
      clinical and geographical sources could be divided into four groups based on
      molecular heterogeneity in silver-stained sodium dodecyl sulfate-polyacrylamide
      gel electrophoresis (SDS-PAGE) profiles in the region of the 10 to 17 kDa. The
      lipopolysaccharide of group 1 was identified on isolates from acute Q fever
      patient, milk and tick. The three remaining groups were primarily found on
      isolates from human cases of chronic Q fever. These LPSs shared many antigenic
      epitopes, as determined by immunoblotting with mouse anti-C. burnetii antisera.

PMID- 9524958
TI  - Anthelmintic efficacy of milbemycin oxime against Trichuris vulpis in dogs.
AB  - The anthelmintic efficacy of milbemycin oxime against dog whipworm, Trichuris
      vulpis, was evaluated. A total of 21 T. vulpis positive dogs were divided into 3
      groups, one (5 dogs) for control and the other two (8 dogs each) for anthelmintic
      treatment with oral administration of milbemycin oxime.

PMID- 9524959
TI  - A possible mechanism for selection of virulent avian influenza A viruses in 14
      day-old embryonated eggs.
AB  - The emergence of virulent avian influenza viruses in poultry is unpredictable. To
      gain insight into the mechanism of this event, we previously examined the
      possible role of older (14-day-old) embryonated eggs, in which virulent mutants
      were preferably selected (Horimoto and Kawaoka, Virology 206: 755-759, 1995).
      However, it is unknown why virulent mutants replicate predominantly in older
      eggs. In the present study, we compared protease activities responsible for
      cleavage activation of the hemagglutinin (HA) in allantoic fluids in 10-day and
      14-day-old eggs. In vitro assays showed that the protease activities were
      stronger in the 14-day-old than 10-day-old eggs. The allantoic fluids with strong
      protease activity degraded HA. These results indicate that replication of
      avirulent viruses is hampered in older eggs, while that of virulent viruses whose
      HAs are activated by other intracellular proteases was not, possibly leading to a
      replicative advantage for virulent mutants in the older eggs.

PMID- 9524960
TI  - Improved electroporation of Rhodococcus equi.
AB  - The condition of an electroporation method was re-evaluated for the introduction
      of foreign plasmid DNA into Rhodococcus equi. The method is based on an
      electroporation of the bacteria made competent by culturing in a broth containing
      glycine and by heat shock at 50 degrees C. Transformation of R. equi could be
      achieved with a chloramphenicol-resistant shuttle vector originating from
      Rhodococcus fascians at an efficiency of about 10(4) transformants/microgram DNA.
      The bacteria were also shown to become competent when they were incubated with a
      chemical transformation buffer prior to washing with an electroporation buffer.

PMID- 9524961
TI  - Action of pituitary and lymphocyte prolactin.
AB  - In vivo and in vitro data combined show that prolactin (PRL) can mimic or
      interact with known lymphocyte cytokines and that these, in turn, can regulate
      PRL synthesis at the site of immune response. In contrast, pituitary PRL is under
      the control of both immune system products (non-cognitive stimuli) and signals to
      the CNS (cognitive stimuli). The role of PRL as a cytokine and as an endocrine
      hormone is discussed. In particular, assignment of PRL to the T helper 1
      phenotype is proposed, based on its ability to enhance NK cell function, activate
      the interferon-regulated factor (IRF-1) transcription factor and to interact with
      or generate IL-2 and IFN gamma. Since hyperprolactinemia and hypoprolactinemia
      are both immunosuppressive, physiological levels of circulating PRL must be
      necessary to maintain normal immunocompetence. Moderate increases in PRL during
      immune stimulation of the hypothalamic-pituitary axis may counteract
      glucocorticoid inhibition, whereas inappropriate prolongation of PRL synthesis
      could lead to autoimmune diseases. Increased release of PRL by the pituitary
      during stress may inhibit NK cell antitumor cytotoxicity. The variety of PRL
      isotypes, the existence of multiple receptor subunits, and the complexity of
      their intracellular signaling may explain the specificity of PRL action on
      different target cells.

PMID- 9524962
TI  - Changes in immunological and neuronal conditions markedly altered antibody
      response to intracerebroventricularly injected ovalbumin in the rat.
AB  - The serum antibody response to ovalbumin (OA) has been investigated following
      intracerebroventricular (i.c.v.) and intravenous administration of antigen in the
      rat, under altered neuronal and immunological conditions. I.c.v. administration
      of antigen was far more potent in eliciting humoral immune response. Central
      nervous system (CNS) immunization under the conditions of disrupted blood-brain
      barrier decreased anti-OA antibody production. Peripheral polyclonal stimulation
      with Bordetella pertussis increased production of specific antibodies to i.c.v.
      injected antigen, while complete Freund's adjuvant had no effect on the immune
      response. These results suggest that CNS compartmentalization of antigen may be
      critical for mounting strong antibody production, and that peripheral polyclonal
      stimulation of the immune system may markedly contribute to the overall intensity
      of the immune response.

PMID- 9524965
TI  - Management of AIDS-associated Kaposi's sarcoma: a multidisciplinary perspective.

PMID- 9524963
TI  - Inhibition of the hypothalamic-pituitary-thyroid axis in response to
      lipopolysaccharide is independent of changes in circulating corticosteroids.
AB  - We have investigated the role of circulating glucocorticoids in the suppression
      of the hypothalamic-pituitary-thyroid (HPT) axis following lipopolysaccharide
      (LPS) injection in rats. Intraperitoneal injection of LPS (2.5 mg/kg) suppressed
      paraventricular nucleus thyrotropin-releasing hormone (TRH) mRNA, pituitary
      thyroid-stimulating hormone (TSH) mRNA and plasma triiodothyronine. In these
      animals LPS also increased paraventricular nucleus corticotropin-releasing
      hormone (CRH) mRNA, pituitary proopiomelanocortin (POMC) mRNA and plasma
      corticosterone levels. To investigate the role of plasma corticosterone in the
      suppression of the HPT axis, we clamped the plasma corticosterone level at
      morning baseline level by bilateral adrenalectomy and corticosterone pellet
      implantation. Ten days after surgery, LPS injection evoked a dramatic increase in
      CRH mRNA and POMC mRNA. Despite the lack of change in plasma corticosterone in
      the corticosterone-clamped rats, LPS was still able to suppress TRH and TSH mRNA
      levels in both corticosterone-clamped and sham-operated rats. These data indicate
      that in response to LPS, suppression of the HPT axis occurs and is independent of
      the LPS-induced increase in plasma corticosterone.

PMID- 9524964
TI  - Blockade of N-methyl-D-aspartate receptor prevents hypoxic neuronal death and
      cytokine release.
AB  - Neuronal mortality, interleukin-1 beta (IL1 beta) and tumor necrosis factor-alpha
      (TNF alpha) release were measured in hypoxic hippocampal neuronal cultures.
      Release of IL 1 beta and TNF alpha was already observed in normoxic cultures, but
      after hypoxia it was increased approximately 2-fold. Pretreatment with 2-amino-5
      phosphonovaleric acid (APV), the N-methyl-D-aspartate (NMDA) receptor antagonist,
      not only decreased neuronal mortality as expected, but also dramatically lowered
      cytokine release. However, there was no relationship between the neuronal
      mortality and the release of each cytokine both in untreated hypoxic cultures and
      in APV-pretreated ones. We conclude that IL 1 beta and TNF alpha release in
      hypoxia are dependent on the activation of the NMDA receptor, but that this is
      not the main mechanism of hypoxia damage in in vitro neuronal cultures.

PMID- 9524966
TI  - Time to stop smoking.

PMID- 9524967
TI  - The effect of supplemental oxygen on apnea and oxygen saturation during pediatric
      conscious sedation.
AB  - PURPOSE: This study compared the effect of supplemental oxygen (O2) on pediatric
      patients' apnea status and oxyhemoglobin saturation during: 1) conscious sedation
      for dental procedures and 2) the recovery period following sedation. METHODS:
      Fourteen child patients (mean age 42 months) sedated with 50 mg/Kg chloral
      hydrate, 25 mg hydroxyzine pamoate, and 1.5 mg/Kg meperidine were treated for two
      separate appointments. The patients received supplemental O2 via nasal cannulae
      at random at one of the two appointments. Following the operative period, all
      patients were monitored sitting upright for an additional 15 min. RESULTS:
      Intraoperative results showed that the risk of apnea was 39% (11/28), with apneic
      events distributed equally between O2 and non-O2 supplemented sedations. The
      overall risk of desaturation was 29% (8/28). Mean SpO2 was always elevated with
      O2 supplementation and the mean difference in O2 versus non-O2 was statistically
      significant. The risk of apnea in the postoperative period was 7% (1/14) for both
      the non-O2 and O2-supplemented patients. The risk of desaturation in the
      postoperative period was 11% (3/28) with one desaturation in a non-O2 and two
      desaturations in O2-supplemented patients. CONCLUSION: We conclude that
      intraoperative O2 supplementation prevents desaturations even in the presence of
      apnea during pediatric conscious sedation.

PMID- 9524968
TI  - Clinical evaluation of new designs for intraoral fluoride-releasing systems.
AB  - PURPOSE: Intraoral fluoride-releasing (IFR) devices provide elevated levels of
      fluoride in the mouth for extended periods of time. However, retention and
      protection of the devices have posed major challenges for clinical applications.
      The objectives of this study were to develop new methods for retaining and
      protecting IFR devices in the mouth and to assess their effects on salivary
      fluoride levels and distribution in adolescents. METHODS: Four different IFR
      systems (combinations of an IFR device and its retainer) were evaluated in four
      groups of 10 adolescents each, 12-15 years of age, for a period of six months.
      Each child wore two IFR systems of a given type affixed to the buccal surface of
      each permanent maxillary first molar. Unstimulated saliva samples were collected
      at each clinical examination and analyzed for fluoride. RESULTS: A significant
      increase in salivary fluoride concentration from a baseline mean of 0.07-0.69
      microgram/mL was observed on day 14 postinsertion. IFR system retention was 85%
      after 6 months and, of the systems retained, 100% were functional. CONCLUSIONS:
      These findings suggest that IFR devices can be successfully protected and
      retained in the mouth for prolonged periods of time.

PMID- 9524969
TI  - Effect of etching on leakage of sealants placed after air abrasion.
AB  - PURPOSE: The aim of the present study was to assess the microleakage of pit and
      fissure sealants in: 1) air-abraded molars with and without etching and 2) in
      preventive resin restorations (PRR) prepared with air abrasion or mechanically
      with a bur. METHODS: Forty molars with no or minimal occlusal caries were cleaned
      with pumice, washed, and assigned to four groups of 10 teeth each. In group A,
      the teeth were air-abraded and Helioseal was applied directly to the fissures
      without previous treatment. Group B was air-abraded and etched for 20 s prior to
      sealant application. In group C, caries was excavated with air abrasion, etched,
      and restored with Scotchbond Multipurpose, Z-100 and Helioseal. Group D was
      similar to C except that the fissures were prepared mechanically with a carbide
      bur at high speed. RESULTS: Group A was significantly different in both Y1 and Y2
      measurements from all the other groups. No differences were observed between all
      the other groups. Acid etching should be a precondition before sealant
      application. Air abrasion and mechanical preparation resulted in the same amount
      of microleakage following acid etch.

PMID- 9524970
TI  - Bacteremia of dental origin and antimicrobial sensitivity following oral surgical
      procedures in children.
AB  - METHODS: The prevalence and intensity of bacteremia of dental origin were
      examined in 207 children divided into four groups: a baseline with no surgical
      intervention (group I), after a single tooth extraction (group II), multiple
      tooth extraction (group III), and mucoperiosteal flap elevation (group IV). The
      bacterial isolates were grown using a broth culture (Bactec) and lysis
      centrifugation (Paediatric Isolator) techniques. Dental plaque deposits,
      gingivitis, spontaneous gingival bleeding and the presence/absence of a dental
      abscess were recorded and their relationship to bacteremia assessed. RESULTS: The
      broth culture was positive for group I 11% of the time, group II for 43%, group
      III for 54%, and group IV for 43%. The Paediatric Isolator system was found to be
      a poor method for detecting bacteremia, having only one quarter the sensitivity
      of the broth culture technique. When organisms were isolated, the intensity of
      bacteremia ranged from 1 to 3400 colony forming units per milliliter (cfu/mL).
      Bacterial isolates were susceptible to most of the antibiotics recommended for
      antibiotic prophylaxis, but erythromycin, gentamycin, penicillin G, and
      teicoplanin were only 80% (or less) effective in their efficacy while
      chlorhexidine, amoxicillin, clindamycin, and vancomycin were between 92 and 100%
      effective. CONCLUSIONS: The antibiotics commonly used for an oral and/or
      parenteral prophylaxis are likely to be effective on at least 80% of occasions
      with most of them effective on 100% of occasions.

PMID- 9524971
TI  - The effects of acid-etching on enamel from different clinical variants of
      amelogenesis imperfecta: an SEM study.
AB  - PURPOSE: Successful bonding of resins to teeth affected by amelogenesis
      imperfecta (AI) may be highly dependent on how the enamel responds to acid
      etching. The aim of this study was to determine, using scanning electron
      microscopy (SEM), the types of etching pattern achieved with 37% phosphoric acid
      on dental enamel of 5 clinical variants of AI, namely, pitted hypoplastic, smooth
      hypoplastic, X-linked (male), X-linked (female), and hypomineralized. METHODS: A
      normal premolar and primary molar from two healthy patients were used as
      controls. The enamel was scanned before and after acid etching for 1 min. In the
      normal, control teeth, the three classical etching patterns were produced: type
      1, in which the prism cores are preferentially removed; type 2, in which the
      prism peripheries are removed, and type 3 in which the removal of enamel does not
      relate to prism structure. RESULTS: In the normal primary molar, patterns of
      types 2 and 3 were generally produced. In the AI teeth, the effects of acid
      etching reflected the clinical variant of AI. All three etch patterns were
      observed in the enamel surrounding the pits in the pitted type of AI and in the
      bands of normal enamel in the female with X-linked AI, as well as in the
      hypomineralized variant. In contrast, no typical etch patterns could be detected
      in the enamel from the male patient with X-linked variant, as well as from the
      enamel affected by the smooth hypoplastic variant. CONCLUSIONS: The lack of
      typical etching patterns in these variants may be the result of abnormal prism
      structure, or the standard etching time and/or acid concentration may be
      inappropriate for the abnormal enamel. The results of this study may have useful
      applications in the restoration of teeth affected by AI.

PMID- 9524972
TI  - Antibacterial properties of current orthodontic band cements.
AB  - PURPOSE: Manufacturers commonly provide information on the physical properties of
      dental materials, but information on their antibacterial properties is often
      missing. This study determined the antibacterial properties of four currently
      used orthodontic band cements against three different strains of Streptococcus
      mutans. METHODS: The cements utilized were Durelon, Ketac, Mizzy Zinc Phosphate,
      and Band-Lok, a recently introduced, resin-based, dual-cure glass ionomer cement.
      Disk diffusion assay methodology was used to test for zones of bacterial
      inhibition around cement samples. Zones of inhibition were measured in
      millimeters using an electronic caliper. In addition to cured cement plugs and
      freshly mixed cement samples, a new variation, in the form of a cement plug
      surrounding a stainless-steel band, was tested. Twelve combinations resulted from
      the four cement types and three forms. RESULTS: Of the variables studied, the mix
      forms of Durelon, Ketac, and Mizzy Zinc Phosphate cement showed the greatest
      bacterial inhibition (Kruskal-Wallis, P < 0.05). Among the cements tested, Mizzy
      Zinc Phosphate showed the largest zones of inhibition, with Durelon and Ketac
      having comparable zones of inhibition (Kruskal-Wallis, P < 0.05). Band-Lok did
      not exhibit an inhibitory effect against any of the three strains of S. mutans
      tested. CONCLUSION: A "containment effect" of no bacterial inhibition was
      observed in the cement samples surrounded by the stainless-steel band material.

PMID- 9524973
TI  - A comparison of a hybrid light-cured glass-ionomer base and liner vs. a light
      cured resin tooth fragment attachment.
AB  - PURPOSE: The purpose of this study was to compare the dislodgement strengths and
      fracture types for reattached tooth fragments using a light-cured composite resin
      material, a hybrid light-cured glass ionomer base, and a hybrid light-cured glass
      ionomer liner. METHODS: Seventy-five bovine incisor teeth were fractured,
      randomly divided into three groups of equal number, and then luted back together
      with three different materials (Universal Bonding Agent/TPH Composite Resin;
      VariGlass VLC Base; and VariGlass VLC Liner: LD Caulk Div Dentsply Int Inc,
      Milford, DE). The reattached fragments were subjected to thermocycling with a 40
      degrees C differential and then were loaded until the force required to dislodge
      the fragment was reached. RESULTS: The mean dislodgement strengths were 36.8 (+/-
      25.6) kg for the composite resin, 36.4 (+/- 26.7) kg for the glass ionomer base,
      and 31.4 (+/- 29.5) kg for the glass ionomer liner. Cohesive fractures occurred
      in 73% of the dislodgements. CONCLUSIONS: There was no statistically significant
      difference demonstrated (P < 0.05) between the three groups in terms of both
      dislodgement strength and fracture type.

PMID- 9524974
TI  - Unilateral delayed eruption of maxillary permanent first molars: four case
      reports.

PMID- 9524975
TI  - Oral aspects and management of severe graft-vs-host disease in a young patient
      with beta-thalassemia: case report.

PMID- 9524976
TI  - Case review section of the American Board of Pediatric Dentistry: stumbling
      blocks and pitfalls.
AB  - The Directors of the American Board of Pediatric Dentistry are eager for eligible
      candidates to become Diplomates. It is important to the profession as well as to
      the individual that more of our colleagues become Board certified. Failure on a
      Section of the examination is distressing to us as well as to the candidate.
      Requirements for the Case Review Section are very specific and are intended to
      assist the candidate in preparing the cases. Carefully following the guidelines
      will minimize potential disappointment.

PMID- 9524977
TI  - Anna-Monika-Prize paper. Major depression and the environment: a psychiatric
      genetic perspective.
AB  - Genetic factors can interact with environmental factors to influence the
      vulnerability to major depression (MD) in subtle ways. I explore two such
      mechanisms: "genetic control of sensitivity to the environment," and "genetic
      control of exposure to the environment." "Genetic control of sensitivity to the
      environment" suggests that genes, in part, render individuals relatively
      vulnerable or relatively invulnerable to the pathogenic effects of environmental
      stress. In support of this hypothesis, evidence is presented that the
      depressogenic effect of stressful life events is substantially greater in those
      at high versus low genetic risk to the MD. "Genetic control of exposure to the
      environment" suggests that genetic factors influence the probability that
      individuals will select themselves into high vs. low risk environments. In
      support of this hypothesis, evidence from a population based twin study suggests
      that certain classes of stressful life events are modestly heritable. The genetic
      risk factors for MD in part express themselves by influencing the probability
      that individuals will experience stressful life events, particularly of an
      interpersonal nature.

PMID- 9524978
TI  - Anna-Monika-Prize paper. The hypothalamic-pituitary-adrenal system in depression.
AB  - Patients with depression frequently have symptom clusters which point strongly to
      involvement of the hypothalamic-pituitary-adrenal (HPA) system as a relay station
      between neurocircuitries in the brain and peripheral hormone and autonomic
      nervous function. It has been proposed that this increased, state-dependent
      hyperactivity of the HPA-system in depression is probably initiated and/or
      maintained by the combination of enhanced central production of CRH and
      desensitization of the binary, glucocorticoid receptor binding system in the
      hippocampus, which is the central regulator of HPA system activity. In a first
      series of studies a refined neuroendocrine test to probe the integrity of HPA
      system status--the combined dexamethasone suppression/CRH challenge (DEX/CRH)
      test--was developed and the differential effects of aging and depressed
      psychopathology on DEX/CRH test outcome were described. In a second set of
      studies, the chronological relationship between improvement of psychopathology in
      depressed patients treated with antidepressants and normalization of the
      disturbed HPA system function in these patients was further elucidated. Given the
      evidence from animal studies, we conclude that antidepressants induce an up
      regulation of hippocampal glucocorticoid receptor mRNA concentration, thus
      amplifying the negative feedback effect of glucocorticoids. This then results in
      the normalization of DEX/CRH test results observed in the depressed patients in
      our study. We further conclude that dampening of HPA system hyperactivity in
      depression by means of antidepressants is a conditio sine qua non for successful
      improvement of psychopathology.

PMID- 9524979
TI  - Comparison of the effects of zolpidem and flunitrazepam on sleep structure and
      daytime cognitive functions. A study of untreated unsomniacs.
AB  - The effects of zolpidem 10 mg, flunitrazepam 1 mg, and placebo, administrated at
      bedtime, were studied in 12 healthy male insomniac patients. The assessments
      included polygraphic sleep recordings during the night and a battery of cognitive
      tests (sign crossing test, dichotic listening test, digit span test, visual
      recognition test and free recall test during four times during the following day.
      Compared with placebo, both active drugs improved sleep parameters. However, with
      zolpidem, the results were not statistically different from placebo. Zolpidem dit
      not alter sleep architecture in contrast to flunitrazepam, which significantly
      increased stage 2 and decreased slow wave sleep and REM sleep. No significant
      interaction was found between time of day for the evaluation of cognitive
      function. Flunitrazepam significantly impaired attention and memory compared with
      zolpidem and placebo, while zolpidem did not differ from placebo. These results
      indicate that zolpidem 10 mg preserved sleep structure and daytime cognitive
      functions in contrast to flunitrazepam.

PMID- 9524980
TI  - Personality correlates of +/- pindolol induced decreases in prolactin.
AB  - The present study was conducted to investigate if personality traits can be
      usefully related to serotonergic vs. dopaminergic action of the 5-HT1a-antagonist
      +/- pindolol. Forty healthy male volunteers (aged between 20 and 30 years) were
      randomly assigned to a placebo or a +/- pindolol (30 mg, oral dose) group in a
      double blind trial. Blood samples were drawn and analyzed for PRL concentrations.
      In addition, the subjects completed questionnaires on personality. The results
      indicated that +/- pindolol decreases PRL concentrations depending on
      personality. While subjects high on impulsivity and related traits (aggression
      and disinhibition) show lower PRL decreases, well-being and personality traits
      frequently related to dopaminergic activity were not correlated with changes in
      PRL. Since reduced (blunted) PRL-responses after 5-HT challenge tests have been
      reported for impulsives, the present results favor the involvement of primarily
      serotonergic and probably only secondarily dopaminergic control of +/- pindolol
      induced PRL decreases.

PMID- 9524981
TI  - An open comparison of clozapine and risperidone in treatment-resistant
      schizophrenia.
AB  - BACKGROUND: Clozapine and risperidone are used in treatment-resistant
      schizophrenia. At present, there are few reported comparisons of these drugs in
      this population. We report on a consecutive series of treatment-resistant
      schizophrenics given either clozapine or risperidone in open clinical trials.
      METHOD: Subjects were treated with clozapine (n = 57) or risperidone (n = 29).
      Pretreatment GAF, CGI, and PANSS scores did not differ between the groups, nor
      did demographic variables including age, age at first hospitalization, years ill,
      number of previous hospitalizations, or gender. The mean treatment trial was 12.1
      weeks, with mean doses of clozapine 420 mg, and risperidone 7.75 mg. The length
      of the trial did not differ significantly between the groups. Response was taken
      to be a 20% decrease in the PANSS score. RESULTS: Using repeated measures ANOVA,
      PANSS total scores (F = 5.3, p = 0.02) and positive subscore (F = 7.4, p = 0.008)
      showed greater improvement in the clozapine group than the risperidone group,
      while other PANSS subscores showed a trend toward greater improvement with
      clozapine. The PANSS-derived factors of excitement (F = 6.7, p = 0.01),
      psychosocial withdrawal (F = 3.8, p = 0.05), and psychomotor retardation (F =
      3.9, p = 0.05) improved more in the group treated with clozapine. The GAF (F =
      10.9, p = 0.0014), CGI (F = 11.5, p = 0.0011), and CGI improvement (p = 0.0001)
      scores also improved more in the clozapine group. Of the clozapine group, 25
      (44%) responded, while 8 (28%) of the risperidone group responded to treatment.
      DISCUSSION: Clozapine had better efficacy in subjects with treatment-resistant
      schizophrenia compared to risperidone, although risperidone appears to yield
      better response rates than those previously reported for typical antipsychotics.
      Double-blind, controlled trials of risperidone are needed to establish its
      efficacy in treatment-resistant schizophrenia.

PMID- 9524982
TI  - SSRI supplementation of antimanic medication in dysphoric mania.
AB  - The authors report on a 42-year-old female inpatient with bipolar I disorder,
      whose dysphoric mania responded rapidly and completely while her antimanic
      medication (lithium, carbamazepine, clozapine, haloperidol and clonazepam) was
      supplemented by 20 mg of paroxetine daily. The practical and theoretical
      importance of this case is briefly discussed.

PMID- 9524983
TI  - Hyponatremia associated with paroxetine.
AB  - Hyponatremia is an uncommon but widely reported complication of selective
      serotonin uptake inhibitors (SSRIs), and most of the case reports involve elderly
      patients. The presentation is usually that of SIADH, but the underlying mechanism
      leading to the syndrome is poorly understood. Since the use of SSRIs is becoming
      more popular among elderly depressed patients and because of the potentially
      serious consequence of hyponatremia, psychiatrists should be alert to the
      development of the complication and familiarize themselves with its diagnosis and
      treatment. We report two elderly patients who were identified to have
      hyponatremia after the commencement of paroxetine. This illustrates the need for
      monitoring of plasma sodium level if a patient's clinical condition deteriorates.
      Other factors possibly related to the hyponatremia are discussed and a review of
      the diagnosis and management of SSRI-related hyponatremia is included.

PMID- 9524984
TI  - Is lamotrigine effective for treatment-refractory mania?

PMID- 9524985
TI  - Anticholinergic toxic syndrome with venlafaxine-desipramine combination.

PMID- 9524986
TI  - Alcohol or drug use and compliance with safer sex guidelines for STD/HIV
      infection. Results from the French National Survey on Sexual Behavior (ACSF)
      among heterosexuals. Analyse des Comportements Sexuels en France.
AB  - BACKGROUND: Available literature shows that association of alcohol and/or drug
      use with unsafe sexual practices is not established, in contradistinction to the
      well-established association between such substance use and the sexual milieu
      itself. GOAL: To analyze these two kinds of associations in a population-based
      sample of heterosexuals in France. STUDY DESIGN: Cross-sectional telephone survey
      of the French adult heterosexual population in the early 1990s (n = 4213).
      RESULTS: Subjects at risk were more likely than those not at risk to have
      consumed alcohol before sex; this was not the case for drug use. However, at-risk
      subjects who engaged in unsafe practice(s) were not more likely to have consumed
      alcohol or drugs. CONCLUSION: Alcohol consumption appears to be a marker for
      being in an at-risk situation in France and may be used as such by public health
      providers. In contrast, the association between alcohol/drug use and unsafe
      sexual practices is not supported by our study and thus conflicts with prevention
      strategies to increase compliance with safer sex through alcohol/drug abstinence.

PMID- 9524988
TI  - Race and sexually transmitted diseases.

PMID- 9524987
TI  - Do differences in sexual behaviors account for the racial/ethnic differences in
      adolescents' self-reported history of a sexually transmitted disease?
AB  - BACKGROUND AND OBJECTIVES: African-American adolescents have the highest rates of
      sexually transmitted diseases (STDs) of any racial/ethnic group of adolescents.
      The objective of this study was to determine the degree to which racial/ethnic
      differences in sexual behaviors account for African-American adolescents' higher
      rates of STDs. STUDY DESIGN: A secondary analysis of data collected as part of
      the Youth Risk Behavior Survey supplement to the 1992 National Health Interview
      Survey was conducted. The sample included 5,189 nationally representative
      civilian noninstitutionalized sexually experienced United States adolescents 14
      to 21 years of age. RESULTS: The age- and sex-adjusted odds ratio (OR) for a
      reported history of an STD for African-American adolescents was 3.86 (95%
      confidence interval [CI] = 1.57, 9.50). The STD risk for African-American youth
      increased with the adjustment for other sociodemographic factors (OR = 4.13; CI =
      1.71, 9.99) and decreased with the adjustment for sexual behaviors (OR = 3.67; CI
      = 1.55,8.66). CONCLUSIONS: Differences in sexual behaviors do not fully account
      for African-American adolescents' increased risk for STDs. Interventions designed
      to reduce sexual risk taking among African-American adolescents may not
      ameliorate racial/ethnic differences in rates of STDs.

PMID- 9524989
TI  - Epidemiologic support to state and local sexually transmitted disease control
      programs. Perceived need and availability. The Field Epidemiology Network for
      STDs (FENS).
AB  - BACKGROUND AND OBJECTIVES: Sexually transmitted diseases (STDs) comprise the
      majority of national infectious disease morbidity reported, yet the number of
      epidemiologists working in state and local STD programs is estimated to be small.
      Even less is known about the training and activities of those epidemiologists.
      GOALS: To determine the number, training, and affiliation of epidemiologists
      working with STD programs and the level of satisfaction with epidemiologic
      support available. STUDY DESIGN: Survey of 65 program managers in state and local
      health departments. RESULTS: Program managers named 146 people working on
      epidemiologic activities, and 84 of those people were classified as
      "epidemiologist" by the criteria we applied. The median number of full-time
      equivalent (FTE) epidemiologists working in or with STD programs was 0.5; one
      quarter of all STD program had no epidemiologists. There was a significant
      association between number of FTE epidemiologist and population, with most
      programs with more than 0.5 epidemiologists located in areas with at least
      1,000,000 population. State Epidemiologists do not provide technical support to
      most state STD programs. Almost half (45%) of all program managers indicated that
      they have inadequate epidemiologic support for routine program activities.
      CONCLUSIONS: The current level of epidemiologic support available to most STD
      programs is inadequate to perform surveillance and data analyses, interpret data
      to develop program objectives, and perform program evaluation. An essential next
      step is the delineation of a set of critical, analytic STD field epidemiology
      functions to define appropriate standards against which epidemiologic capacity
      can be more precisely measured.

PMID- 9524990
TI  - Prenatal human immunodeficiency virus and sexually transmitted disease screening.
      Getting the message across.

PMID- 9524992
TI  - Do spermicides containing nonoxynol-9 prevent sexually transmitted infections? A
      meta-analysis.
AB  - BACKGROUND AND OBJECTIVES: There are conflicting opinions on whether to recommend
      spermicides containing nonoxynol-9 for prevention of sexually transmitted
      diseases, including human immunodeficiency virus (HIV). GOAL: To systematically
      review and summarize the medical literature on the effect of spermicides
      containing nonoxynol-9 on prevention of gonorrhea, chlamydial infection, and HIV.
      STUDY DESIGN: Meta-analysis. Potential articles were identified through
      computerized literature searches. Articles were included if the design was
      clinical trial, cohort, case-control, or cross-sectional; original outcome data
      were presented for gonorrhea, chlamydial infection, or HIV; and spermicides
      containing nonoxynol-9 were used separately from other barrier methods. Study
      characteristics including design, population, spermicide dose, and delivery
      method were abstracted. Relative risks (RR) and 95% confidence intervals (CI)
      were determined from information published in the study or from study authors.
      Summary risk estimates were computed for clinical trials. RESULTS: Twelve
      eligible articles were identified, including six clinical trials and six
      observational studies. Eleven articles evaluated gonorrhea; each found a reduced
      risk of infection with spermicide use. Among six clinical trials, the summary RR
      was 0.62 (95% CI, 0.49-0.78). The five articles evaluating chlamydial infection
      also found significant reduction among spermicide users, with the four clinical
      trials having a summary RR of 0.75 (95% CI, 0.62-0.91). The degree of spermicidal
      protection against gonorrhea and chlamydial infection did not differ materially
      among studies with different study designs or spermicidal preparations (i.e.,
      sponge, gel, suppository, or film). Three studies evaluated degree of protection
      according to consistency of use and found stronger protection with more
      consistent use. The two studies on spermicidal prevention of HIV had contrasting
      results: An observational study found a significant protective effect (RR = 0.1),
      whereas a clinical trial found a nonsignificantly increased risk (RR = 1.7).
      CONCLUSIONS: Nonoxynol-9-containing spermicides have an appreciable protective
      effect against both gonorrhea and chlamydial infection, and wider use of
      spermicides might substantially reduce the incidence of these diseases. However,
      insufficient data exist to judge their effect on HIV transmission, and more
      research on the effect of nonoxynol-9 on HIV transmission is urgently needed to
      make evidence-based clinical decisions and public health recommendations in the
      future.

PMID- 9524991
TI  - Increasing barrier method use among oral contraceptive users at risk of STDs.
      What approach is best?
AB  - OBJECTIVES: We evaluated whether offering a choice of barrier methods can
      increase overall barrier method use without decreasing condom use in women using
      oral contraceptives (OCs) for contraception. STUDY DESIGN: We randomized 167 OC
      users at risk for sexually transmitted diseases (STDs) into two groups, one
      receiving male latex condoms only (Condom group), the other receiving both male
      latex condoms and nonoxynol-9 film (Choice group). All participants received
      similar hierarchical STD protection counseling. We assessed method use with daily
      diaries. RESULTS: The Choice group protected a significantly higher percentage of
      their coital acts with a barrier method (month 1 to 2: 29% vs. 22%; month 3 to 4:
      33% vs. 21%; and month 5 to 6: 35% vs. 19%; adjusted P = 0.012). Condom use in
      the Choice group was higher as well (adjusted P = 0.036). When we used a
      transitional multilogistic regression approach to account for differential loss
      to follow-up in the two groups, results were similar. CONCLUSIONS: Offering a
      choice of barrier methods increased overall barrier method use without decreasing
      condom use.

PMID- 9524993
TI  - Microbicides, meta-analysis, and the N-9 question. Where's the research?

PMID- 9524994
TI  - Using social network and ethnographic tools to evaluate syphilis transmission.
AB  - BACKGROUND AND OBJECTIVES: Partner notification has been the cornerstone for the
      prevention and control of syphilis in the United States. This technique may not
      make full use of contextual data that an ethnographic and social network approach
      can offer. GOALS OF THE STUDY: The occasion of a syphilis outbreak among young
      people was used to investigate the applicability of a social network approach and
      to test the validity of several traditional approaches to syphilis epidemiology.
      STUDY DESIGN: An outbreak of syphilis was investigated by interviewing both
      infected and noninfected people, by directing resources based on network
      association, by creating and evaluating network diagrams as an aid to the
      epidemiologic process, and by including ethnographic observations as part of
      outbreak management. RESULTS: Diagrammatic display of network growth provided a
      useful alternative to the traditional epidemic curve. Case prevention was
      demonstrated by identifying uninfected people with multiple concurrent exposures.
      Concurrent, overlapping exposure in infected people rendered traditional "source"
      and "spread" criteria moot. CONCLUSIONS: The current discussions of partner
      notification may be informed by recognizing that it is a subset of a broader and
      potentially more powerful approach. This approach calls some basic tenets of
      syphilis epidemiology into question.

PMID- 9524995
TI  - Reductions in STD infections subsequent to an STD clinic visit. Using video-based
      patient education to supplement provider interactions.
AB  - BACKGROUND AND OBJECTIVES: Video-based patient education has been effective in a
      variety of clinical settings. The authors studied the efficacy of a video-based
      educational intervention in an inner-city public sexually transmitted diseases
      (STD) clinic. GOAL: To evaluate the efficacy of video-based patient education in
      reducing STD infections subsequent to a clinic visit. DESIGN: African-American
      and Hispanic men attending a large public STD clinic were assigned at random to
      either an experimental video-based educational intervention or a control
      condition in which they received regular clinic services. Patients in the
      experimental group were exposed to video-based interventions that provided
      information about STDs and their prevention, portrayed positive attitudes about
      condom use, and modeled appropriate strategies for encouraging condom use in
      different sexual relationships. During 1992, 2,004 subjects were tracked for an
      average of 17 months through the New York City STD surveillance database for the
      occurrence of new STD infections. RESULTS: The overall rate of new infection
      among male STD clinic patients was 24.2%. Rate of new infection was significantly
      lower among those exposed to video-based prevention education than among controls
      (22.5% compared with 26.8%, p < .05). Subjects reporting multiple sex partners
      had a significantly higher new infection rate but also experienced the greatest
      impact of educational intervention. There was a 32.2% new infection rate among
      high-risk controls compared with a 24.8% rate among high-risk intervention groups
      (p < 0.025). CONCLUSION: Results of this randomized clinical trial indicate that
      using video-based patient education to supplement regular STD clinic services and
      provider interactions can be effective in reducing rates of new STD infection,
      particularly among those at greatest risk.

PMID- 9524996
TI  - Physicians' practices and opinions regarding prenatal screening for human
      immunodeficiency virus and other sexually transmitted diseases.
AB  - BACKGROUND AND OBJECTIVES: Early prenatal diagnosis of sexually transmitted
      diseases (STDs), particularly human immunodeficiency virus (HIV), is critical for
      maternal and infant health. We conducted a survey to assess physicians' prenatal
      STD screening practices and opinions. STUDY DESIGN: A random sample of
      obstetricians and family physicians was selected from the Minnesota Medical
      Association directory to complete a standardized telephone survey. RESULTS:
      Eighty-three (86%) of 96 eligible obstetricians and 94 (95%) of 99 eligible
      family physicians completed the survey. Nearly all physicians recommend universal
      prenatal screening for syphilis (97%) and hepatitis B (99%); fewer physicians
      recommend prenatal screening for HIV (43%), chlamydia (26%), and gonorrhea (24%).
      Adjusting for physicians' specialty, female physicians were more likely than male
      physicians to recommend universal prenatal HIV screening (odds ratio [OR] = 2.1;
      95% confidence interval [CI] = 1.1-4.2). Adjusting for physicians' ages,
      physicians with more than 20% uninsured/Medical Assistance patients were more
      likely than other physicians to recommend prenatal gonorrhea screening (OR = 3.1;
      95% CI = 1.4-6.8); similar factors were associated with chlamydia screening.
      Although 89% of physicians supported universal prenatal HIV counseling and
      voluntary screening, the median percentage of prenatal patients screened for HIV
      was only 10%. CONCLUSIONS: Most physicians reported routinely screening prenatal
      patients for syphilis and hepatitis B. Although many physicians agreed with
      recommendations for universal prenatal HIV screening, their reported screening
      practices varied considerably from this approach.

PMID- 9524997
TI  - A pilot study of metronidazole vaginal gel versus oral metronidazole for the
      treatment of Trichomonas vaginalis vaginitis.
AB  - BACKGROUND: Trichomonas vaginalis is a common sexually transmitted pathogen. In
      the United States, oral metronidazole is the only officially sanctioned treatment
      option. OBJECTIVE: This study was undertaken to compare the efficacy and safety
      of 0.75% metronidazole vaginal gel with that of oral metronidazole for the
      treatment of trichomonal vaginitis. STUDY DESIGN: Women with trichomoniasis were
      enrolled in this randomized, open-label pilot study of 0.75% metronidazole
      vaginal gel twice daily for 7 days compared with 7 days of generic oral
      metronidazole, 250 mg, three times daily. Patients were seen for follow-up visits
      5 to 7 days and 21 to 28 days after the last dose of medication. RESULTS: Using
      culture for test of cure, trichomonal infection was eliminated in all 15 women
      treated with oral metronidazole and 7 (44%) of 16 women treated with intravaginal
      metronidazole. Adverse events were similar, except that there were more taste
      related adverse events in the oral metronidazole group. Significant reductions in
      genitourinary symptoms were seen in both the oral and intravaginal groups.
      CONCLUSION: This study has shown that 0.75% metronidazole vaginal gel is not
      effective as a single agent for the treatment of trichomoniasis. Future studies
      may define a role for metronidazole gel for symptomatic relief in patients
      intolerant of oral medication or as adjunctive treatment with oral metronidazole
      for the management of patients infected with metronidazole-resistant strains of
      T. vaginalis.

PMID- 9524998
TI  - Gene therapy in cardiovascular surgery.

PMID- 9524999
TI  - Diffusely infiltrative squamous cell carcinoma of the esophagus.
AB  - This study was designed to clarify the clinical and pathologic features of
      diffusely infiltrative squamous cell carcinoma of the esophagus. Diffusely
      infiltrative squamous cell carcinomas were classified grossly into two types,
      namely, scirrhous carcinoma and nonscirrhous carcinoma. There were seven patients
      with the former type and three with the latter type. Scirrhous-type carcinoma was
      associated with a prominently thickened esophageal wall with strictures, whereas
      nonscirrhous-type carcinoma demonstrated thickening of the esophageal wall
      without strictures. Microscopically, all patients had lymph node metastases and
      lymphatic invasion. Blood vessel invasion was found in seven patients and
      extranodal invasion was found in seven. The prognosis of patients with both types
      of carcinoma was extremely poor. Only two patients who underwent curative surgery
      as well as chemoradiotherapy survived for more than 1 year. Therefore, further
      morphological studies on the early stages of diffusely infiltrating esophageal
      carcinoma should be performed. New treatment strategies such as intensive
      preoperative chemoradiotherapy based on sensitivity tests in individual patients
      will be required for treating the advanced stages of this disease.

PMID- 9525000
TI  - Gastric emptying after pylorus-preserving gastrectomy in comparison with
      conventional subtotal gastrectomy for early gastric carcinoma.
AB  - It is well known that surgical intervention on the stomach will greatly alter
      gastric function and gastric emptying. In this study, we evaluated the difference
      in postoperative gastric remnant emptying following pylorus-preserving
      gastrectomy (PPG) and conventional subtotal gastrectomy (CDG) using
      sulfamethizole capsule food. The subjects comprised 18 patients who underwent PPG
      and 23 who underwent CDG for early gastric carcinoma. While delayed gastric
      emptying was observed early after PPG, 1 year after PPG it was markedly
      accelerated compared with that measured in the early postoperative period.
      However, it was slower than that in the CDG patients. On the other hand, rapid
      gastric emptying was observed early after CDG and did not change with time. These
      findings stress that although PPG results in stasis in the early postoperative
      period, it seems to prevent unduly rapid emptying.

PMID- 9525001
TI  - The relationship of Helicobacter pylori colonization, the serum pepsinogen A
      level, and gastric resection.
AB  - The serum levels of pepsinogen A (PGA) were measured in patients who underwent
      various forms of gastric resection to assess whether Helicobacter pylori (HP)
      colonization has any influence. Included in this study were 48 patients who
      underwent subtotal gastrectomy for a peptic ulcer (SGPU), 36 who underwent
      radical subtotal gastrectomy for gastric carcinoma (SGGC), 16 who underwent
      truncal vagotomy plus antrectomy (TV + AE), 24 with recurrent ulcer (RU) and 27
      who underwent total gastrectomy (TG). The mean serum PGA levels in these five
      groups and in 40 healthy controls were 49.1 +/- 30.4 ng/ml, 30.0 +/- 14.8 ng/ml,
      44.8 +/- 21.7 ng/ml, 66.4 +/- 42.8 ng/ml, 8.7 +/- 3.0 ng/ml, and 94.7 +/- 27.9
      ng/ml, respectively. All patients except those with RU showed a diminished PGA
      level. The HP colonization rates of the patients who underwent partial resection
      were 45.8%, 22.2%, 50%, and 54.2%, respectively (P < 0.05). Age, gender, smoking,
      the type of gastroenterostomy, and underlying disease did not exert any influence
      on the measured PGA levels. However, higher PGA levels were observed in HP
      colonized patients who either underwent SGPU or had RU. We conclude that various
      forms of distal gastrectomy, but not RU, elicit an indistinguishable acid
      secretory ability while HP colonization is responsible for the higher serum PGA
      levels in some patients following peptic ulcer surgery.

PMID- 9525003
TI  - Long-term results of endarterectomy, anatomic bypass and extraanatomic bypass for
      aortoiliac occlusive disease.
AB  - Over the past 20 years, 214 patients in our hospital were operated on for
      aortoiliac occlusion, including an endarterectomy for 88 legs in 64 patients, an
      anatomic bypass for 178 legs in 105 patients, and an extraanatomic bypass for 51
      legs in 45 patients. The extraanatomic group was older than the other two groups
      (70 years versus 64 years), and also showed a higher instance of critical
      ischemic symptoms than the other groups (49% versus 16%). The 10-year primary
      patency rate was 88% for an endarterectomy, 91% for an anatomic bypass, and 73%
      for an extraanatomic bypass. The 10-year survival rate was 71% for an
      endarterectomy, 49% for an anatomic bypass, and 24% for an extraanatomic bypass.
      The possible complications related to each surgical method included sexual
      dysfunction resulting from endarterectomy, and graft infection and anastomotic
      aneurysm in the prosthetic bypass. No ischemic symptoms in the donor limb were
      noted following an extraanatomic bypass. The selection of the appropriate
      surgical method for aortoiliac occlusion should thus be made after a careful
      review of the patient's general condition, the morphology of arterial occlusion,
      and the risk of possible complications for each type of surgery.

PMID- 9525002
TI  - Apoptosis as a prognostic factor in colorectal carcinoma.
AB  - We investigated the occurrence of apoptotic cell death in 104 colorectal
      carcinomas by terminal-deoxynucleotidyl-transferase-mediated dUTP-diotin nick end
      labeling (TUNEL) to determine whether apoptosis could be a useful prognostic
      factor. The apoptotic index (AI) was calculated as the percentage of positive
      cancer cells per 1,000 cancer cells, the median AI being 4.1, with a range of 1.9
      4.7. Apoptosis was less frequently observed in tumors with higher malignant
      potential, such as those at advanced stages Dukes B, C and D, than those at Dukes
      stage A (P < 0.05); in tumors showing evidence of moderate differentiation than
      in well-differentiated tumors (P < 0.05); and in tumors with venous invasion or
      lymph node metastasis than in those without these features (P < 0.05). Moreover,
      the subgroup of patients with a low AI of < 4.1 had a significantly poorer
      survival rate than the subgroup with a high AI in tumors at Dukes stage C, the 5
      year survival rates being 33% vs 68% (P < 0.05; Cox-Mantel). Our findings suggest
      that less apoptosis might result in a greater progression of colorectal
      carcinoma, and that the rate of apoptosis might be an indicator of the degree of
      malignancy. Thus it would appear that the frequency of apoptosis in tumor cells
      could be a useful prognostic factor in colorectal carcinoma.

PMID- 9525004
TI  - Limb salvage and survival rates among elderly patients with advanced limb
      ischemia.
AB  - The purpose of this study was to clarify the incidence of limb salvage and
      patient survival rates among elderly patients with advanced leg ischemia. We
      reviewed the records of 159 patients treated for advanced ischemia over a 15-year
      period at Aichi Medical University, 74 of whom were aged over 75 years and 85,
      between 65 and 74 years. There was a collective total of 186 limbs; 82 in the
      older group and 104 in the younger group. The older group had a greater
      proportion of women, and a higher incidence of coronary heart disease, pulmonary
      dysfunction, and acute onset of advanced ischemia than the younger group. Limb
      salvage was achieved in 73% of the affected limbs in the older group and in 92%
      of the limbs in the younger group. The poor limb salvage rate in the older group
      was mainly related to the high initial amputation rate. Early recognition of the
      sentinel ischemic signs before the ischemia is essential, especially in the
      elderly. Timely revascularization should be attempted whenever possible, and it
      should not be abandoned simply because the patient is deemed too old. The 1-, 3-,
      and 5-year survival rates in the older group were 59%, 28%, and 23%,
      respectively, which were markedly poorer than the expected survival rates of the
      age- and sex-matched Japanese population at 1, 3, and 5 years, which were 93%,
      79%, and 65%, respectively. Thus, advanced limb ischemia carries a poor prognosis
      to the point of being life-threatening, and further continuous systemic
      management with the collaboration of physicians and surgeons must be provided
      even after the patient has left the hospital.

PMID- 9525005
TI  - The surgical treatment of lung lacerations and major bronchial disruptions caused
      by blunt thoracic trauma.
AB  - The records of 16 patients who suffered blunt thoracic trauma, causing lung
      lacerations in 13, bronchial disruptions in 2, and lung laceration with bronchial
      disruption in 1, were reviewed to investigate the correlations between clinical
      factors and prognosis. The causes of these injuries included 14 traffic accidents
      and 2 construction-related accidents, and the indications for surgery were
      massive bleeding in 12 patients, massive air leakage in 2, both in 1, and lung
      abscess in 1. Of the 16 patients, 11 (68.8%) underwent thoracotomy less than 4 h
      after admission, 3 (18.8%) underwent thoracotomy 4 to 24 h after admission, and 2
      (12.5%) underwent thoracotomy 24 h or later after admission. The operative
      techniques included 1 pneumonectomy, 5 lobectomies, 2 bronchoplasties, and 8
      minor repairs. The mortality rate was 43.7%, which included six early deaths
      occurring within 72 h of the trauma, and one late death. While major bronchial
      disruption is usually associated with a good prognosis, univariate and
      multivariate analyses demonstrated that intrapleural bleeding of 300 ml/h or more
      from time of trauma to chest tube drainage was significantly correlated with a
      poor prognosis. Moreover, an injury severity score (ISS) of 36 or more showed a
      trend toward a correlation with poor prognosis in patients with lung lacerations.
      Prompt thoracotomy will decrease mortality rate of patients suffering lung
      lacerations resulting in intrapleural bleeding of more than 300 ml/h.

PMID- 9525006
TI  - Diagnostic potential and pitfalls of ultrasound-guided fine-needle aspiration
      cytology for breast lesions.
AB  - Ultrasound (US)-guided fine-needle aspiration cytology (FNAC) is now widely
      accepted as a diagnostic procedure for breast lesions. Along with its advantages,
      US-guided FNAC also has some pitfalls. The recognition of these pitfalls for this
      procedure is extremely important for the strict management of the disease. We
      retrospectively investigated the diagnostic potential and pitfalls of US-guided
      FNAC in the diagnosis of breast lesions. This study consisted of 348 aspirated
      samples from 274 breast tumors. The rate of sufficient aspirates was 74% after a
      single aspiration, while sufficient materials were finally obtained from 93% of
      the tumors by repeated aspirations. The rate was lower in tumors measuring less
      than 10 mm in diameter (62%), and in sclerosing adenosis (25%). The sensitivity
      of FNAC was 65%, the specificity was 75%, the border diagnosis rate was 18%, and
      the positive predictive value was 92%. The false-negative rate was higher in
      noninvasive carcinoma (45%). The border diagnosis rate was also higher in
      scirrhous carcinoma (29%). There were also five false-positive cases. Limited to
      nonpalpable lesions, the sufficient aspirates rate was 70% and the accuracy was
      67%.

PMID- 9525007
TI  - The first cooperative living-related donor liver transplantation performed by two
      separate institution teams: The Kanagawa Liver Transplantation Program.
AB  - With the cooperation of surgeons in two separate institutes, living-related donor
      liver transplantation was safely performed at the Kanagawa Children's Medical
      Center. The donor operations were carried out at Kanagawa Cancer Center by
      surgeons of the hepatobiliary division and the liver grafts were immediately
      transported to Kanagawa Children's Medical Center by ambulance, and transplanted
      orthotopically. Since January 1995, five children with biliary atresia have been
      given partial liver grafts obtained from their mothers. The liver grafts were
      transported within 20 min, and functioned immediately after transplantation. The
      development of a pediatric liver transplantation program requires a
      multidisciplinary approach that can be provided only in a large tertiary referral
      children's medical center. Preparation for the clinical program involves training
      of surgical and nursing team members, both in an animal laboratory and at an
      established liver transplantation center. Special support for the program by the
      institute is essential and involves medical, nursing, and administrative
      divisions as well as social services, operating room personnel, and intensive
      care unit facilities. After careful planning, and with the invaluable help of the
      donor operating team, the Kanagawa Liver Transplantation Program has been
      realized, and its first transplantations conducted safely and successfully.

PMID- 9525008
TI  - The effects of adenosine on the energy metabolism of the reperfused intestine in
      rats.
AB  - The effects of adenosine on energy metabolism in the intestine during reperfusion
      after intestinal ischemia were examined in rats subjected to intestinal ischemia
      for 60 min by clamping the superior mesenteric artery, followed by 20 min
      reperfusion with tested agents. The rats were divided into a control group, a 200
      micrograms adenosine group, a 500 micrograms adenosine group, and a 500
      micrograms adenine group. Jejunal tissues were taken preischemia, 30 and 60 min
      post-ischemia, and 20 min after starting reperfusion. Adenosine triphosphate, 
      diphosphate, -monophosphate, and thiobarbituric acid reactive substances (TARS)
      of lipid peroxidation were measured by high-performance liquid chromatography or
      spectrophotometry. The ATP levels in the jejunal tissues decreased extensively 30
      min after ischemia, but no further decrease was observed 60 min after ischemia.
      These levels recovered slowly 20 min after starting reperfusion in the control
      group, but they recovered significantly in the 500 micrograms adenosine group and
      moderately in the adenine group, with no significant difference between the 200
      micrograms adenosine and control groups. Thus, the effect of adenosine on energy
      metabolism appears to be dose-dependent. The TARS levels increased significantly
      during ischemia and reperfusion, but no significant difference was observed
      between the control and 500 micrograms adenosine groups. In conclusion, adenosine
      promotes the rapid resumption of ATP levels during reperfusion, but adenine is
      less effective. Adenosine does not affect lipid peroxidation mediated by free
      radicals.

PMID- 9525009
TI  - Downregulation of cytokine-induced neutrophil chemoattractant and prolongation of
      rat liver allograft survival by interleukin-10.
AB  - We investigated whether the administration of recombinant human interleukin-10
      (rhIL-10) regulates the production of cytokine-induced neutrophil chemoattractant
      (CINC) and improves graft survival in rat orthotopic liver transplantation
      (OLTx). Allograft recipients received injections of rhIL-10 at doses of 2, 10,
      20, or 50 micrograms/kg/day. The allograft recipients that received rhIL-10 at 10
      or 20 micrograms/kg/day showed a slight but significant prolongation of graft
      survival to 13.0 +/- 0.4 and 13.8 +/- 0.3 days, respectively, compared with 9.6
      +/- 0.2 days in untreated allografts. Conversely, the administration of high-dose
      rhIL-10 shortened the allograft survival. In the rhIL-10 treatment groups, the
      mean serum and tissue levels of CINC at every time point after OLTx were reduced
      significantly compared with those in the no-treatment group. The mean peak
      neutrophil counts in the peripheral circulation (PC) of the groups given rhIL-10
      at 10, 20, or 50 micrograms/kg/day from the samples obtained 12h after
      reperfusion were decreased significantly compared with the no-treatment group.
      Furthermore, the mean peak neutrophil counts in the PC of the groups given rhIL
      10 at 10 or 20 micrograms/kg/day from the samples obtained between postoperative
      days (PODs) 7 and 10 were decreased significantly compared with the no-treatment
      group. The magnitude of liver damage and leukocyte infiltration in the rhIL-10
      treated allografts on PODs 1 and 7 was reduced compared with that of untreated
      allografts. Our data indicate that the administration of rhIL-10 downregulates
      CINC production during the period of reperfusion injury and acute cellular
      rejection after OLTx, and prolongs liver allograft survival, suggesting that IL
      10 therapy is potentially beneficial in OLTx.

PMID- 9525010
TI  - Does potassium ion concentration affect lung preservation?
AB  - To evaluate the influence of potassium ion concentration in an organ preservation
      solution on lung preservation, four types of solutions were produced. These
      preservation solutions consisted of sodium and potassium ions on the cation and
      phosphate ions on the anion with glucose. Contents of solutions were: (1) 155
      mmol/l Na+, 0 mmol/l K+; (2) 150 mmol/l Na+, 5 mmol/l K+; (3) 20 mmol/l Na+, 135
      mmol/l K+; and (4) 0 mmol/l Na+, 155 mmol/l K+. All four solutions possessed the
      same osmolarity, the same pH in the same temperature, and the same buffer action.
      Lungs were preserved at 7 degrees C in these solutions for 24 h and evaluated in
      a rat lung perfusion system with perfluorochemical emulsion. Pressure-limited
      perfusions with pressure-limited ventilation were carried out for 20 min before
      and after preservation. Thereafter, the recovery ratios of pulmonary arterial
      flow (Q), tidal volume (VT), oxygen tension of the pulmonary venous effluent
      (PPVO2), and wet-to-dry ratios were compared. The recovery ratios of Q were
      better in low, but not zero, potassium solutions, whereas wet-to-dry ratios were
      kept lower in high potassium solutions. No difference in pulmonary compliance or
      gas exchange was observed against a great change in potassium ion concentration.
      Therefore, the potassium ion concentration did not play a major role in lung
      preservation.

PMID- 9525011
TI  - Simultaneous resection of gastric carcinoma and splenectomy in a patient with
      polycythemia vera: report of a case.
AB  - We report herein the case of a 57-year-old man who underwent resection of gastric
      carcinoma after being treated for polycythemia vera (PV) for 16 months. He was
      admitted with gastrointestinal bleeding; barium meal roentogenogram and
      endoscopic examination subsequently revealed a Borrmann type II carcinoma in the
      cardia of the stomach with extension into the lower esophagus. Thus, a lower
      esophagogastrectomy, distal pancreatectomy, splenectomy, and lymph node
      dissection were performed. Although an insufficiency of the esophagojejunal
      anastomosis occurred, the patient suffered no hematologic complications in the
      setting of careful myelosuppressive and antiplatelet coagulation therapy. He is
      currently doing well 5 years after his operation, with grade 1 performance status
      and no signs of recurrence or any hematologic complications.

PMID- 9525012
TI  - Endobronchial metastasis from rectal adenocarcinoma: report of a case.
AB  - We herein report a case of late endobronchial metastasis after the resection of a
      primary rectal adenocarcinoma. A 51-year-old man underwent a resection of rectal
      adenocarcinoma. Five years postoperatively, he underwent a right sleeve upper
      lobectomy for a right endobronchial tumor. The resected tumor was diagnosed to be
      endobronchial metastasis from rectal adenocarcinoma. Therefore, the relationship
      between the two tumors was analyzed using deoxyribonucleic acid (DNA) flow
      cytometry and immunohistochemical staining. Endobronchial adenocarcinoma had
      strong homogeneous staining patterns and identical biochemical characteristics to
      rectal adenocarcinoma.

PMID- 9525013
TI  - Adenocarcinoma arising in the retrorectal space: report of a case.
AB  - We herein present an extremely rare case of adenocarcinoma of unknown origin
      arising in the retrorectal space. The imaging and endoscopic findings misled us
      to preoperatively diagnose a "submucosal tumor." This histological findings were
      highly suggestive of adenocarcinoma, and its unexpected early and aggressive
      recurrence required thorough investigation on the true cell type and its origin.
      Both radiochemotherapy findings and conclusive findings of immunohistochemical
      staining finally revealed this tumor to be an ordinary adenocarcinoma. It was
      impossible to identify its origin histologically, because this case was so
      advanced that it had already replaced the entire entity with adenocarcinoma
      without leaving any clues as to its former nature. We thus assumed this tumor to
      be an adenocarcinoma of unknown origin arising in the retrorectal space.

PMID- 9525014
TI  - Nonfunctional paraganglioma of the pancreas: report of a case.
AB  - We report herein the case of a 61-year-old man found to have a rare nonfunctional
      paraganglioma of the pancreas. Interestingly, the preoperative data and images
      showed similar characteristics to neuroendocrine tumors of the pancreas. Both
      paragangliomas and neuroendocrine tumors of the pancreas belong to the category
      of Amine Precursor Uptake and Decarboxylation (APUD) tumors (APUDomas). Thus, it
      is important to examine the serum level of pancreatic endocrine hormones and a
      variety of peptides to differentiate paragangliomas of the pancreas from other
      pancreatic tumors. Paragangliomas of the pancreas grow slowly, so radical
      resection is recommended to achieve curability with a good prognosis.

PMID- 9525015
TI  - Isolated mediastinal Hodgkin's disease mimicking thymoma: report of a case.
AB  - Mediastinal Hodgkin's disease has rarely been reported in the literature in
      Japan; however, it is not uncommon in Europe and North America. A 32-year-old
      woman with isolated mediastinal Hodgkin's disease mimicking thymoma is herein
      described. A preoperative diagnosis of thymoma led to a combined resection of the
      mediastinal tumor together with the entire thymus, left innominate vein, and left
      phrenic nerve. The resected tumor was histologically diagnosed to be Hodgkin's
      disease of the nodular sclerosis type. Adjuvant 40 Gy irradiation of the
      mediastinum and neck was added postoperatively. The patient is doing well at
      present with no signs of recurrence 8 months after the operation.

PMID- 9525017
TI  - Secretory carcinoma of the breast in an elderly woman: report of a case.
AB  - We herein report a case of secretory carcinoma of the breast in a 73-year-old
      woman. Secretory carcinoma is an extremely rare tumor and demonstrates
      distinctive pathologic characteristics. This tumor frequently occurs in either
      children or adolescents, and thus has been called juvenile carcinoma. We
      encountered this rare tumor in an elderly woman. Aspiration biopsy cytology was
      performed twice, but the cytological diagnosis was not carcinoma. Such pathologic
      characteristics as mild atypia, the absence of hyperchromasia, and a minimal
      degree of pleomorphism in the tumor cells can thus lead to a cytological
      misdiagnosis. An excisional biopsy was performed and secretory carcinoma was
      finally diagnosed. Consequently, a modified radical mastectomy (Kodama's method)
      was performed 7 days later. We describe this very rare tumor's clinicopathologic
      characteristics.

PMID- 9525016
TI  - Thoracotomy for a patient with Stevens-Johnson syndrome: report of a case.
AB  - Stevens-Johnson syndrome (SJS) is an uncommon eruptive disorder of the skin and
      mucous membranes with systemic manifestation. It is extremely unusual for
      patients with a past history of SJS to present with indications for surgery
      necessitating thoracotomy. We describe herein the perioperative management of a
      patient with SJS who underwent surgery for a spontaneous pneumothorax.

PMID- 9525018
TI  - Ovarian teratoma with gliomatosis peritonei: report of two cases.
AB  - Gliomatosis peritonei, a rare condition related to ovarian teratomas, involves
      the peritoneal implantation of numerous nodules of predominantly mature glial
      tissues. We report herein the cases of two patients with immature ovarian
      teratoma associated with gliomatosis peritonei, in one of whom a rapid
      progression of teratomatous implants occurred 14 weeks after her initial surgery.
      Gliomatosis peritonei is considered benign in most cases; however, some reports
      have documented the rapid recurrence of immature peritoneal implants, as
      implantation is associated with teratomas of all grades. Thus, in the face of
      peritoneal implants suspected to be of a teratomatous nature, thorough and
      extensive sampling is essential to exclude the presence of immature elements
      which may imply a poor prognosis and require aggressive therapy.

PMID- 9525019
TI  - Postoperative abnormal prothrombinemia in patients with cefoperazone: report of
      two cases.
AB  - Two cases of postoperative abnormal prothrombinemia presumably caused by the
      administration of cefoperazone are herein described. One patient, who had bile
      duct cancer with obstructive jaundice, underwent resection of the extrahepatic
      bile duct with hepaticojejunostomy (Roux-en-Y anastomosis) and partial resection
      of the liver following percutaneous transhepatic cholangial drainage. He
      developed abnormal prothrombinemia and bleeding 10 days after surgery. The other
      patient, who had undergone a total gastrectomy 17 years earlier, suffered from
      pulmonary tuberculosis. She was initiated anti-tuberculous regimen and
      simultaneously was worked-up for her severe anemia, and was found to have
      ascending colon cancer. She underwent a right hemicolectomy, cholecystectomy, and
      repair of ventral incisional hernia, and subsequently developed abnormal
      prothrombinemia and bleeding 12 days after surgery. Both patients received a
      chemical bowel preparation prior to surgery. Prothrombin time was normal
      preoperatively in both patients. Both patients were treated with fresh frozen
      plasma and intravenous menatetrenon, which improved the clotting disorder within
      24h. Antibiotics containing the N-methyl-thio-tetrazol side chain should thus be
      used with particular prudence in patients with abnormal prothrombinemia and a
      tendency to develop bleeding disorders.

PMID- 9525020
TI  - Epidural administration of droperidol suppresses cisplatin-induced emesis:
      preliminary findings.
AB  - To evaluate the antiemetic effect of the epidural administration of droperidol on
      cisplatin-induced emesis, nine adult gastric cancer patients receiving
      intraoperative cisplatin chemotherapy were studied. After removal of the stomach,
      0.05 mg/kg droperidol with 5 ml saline was injected into the epidural space
      through the epidural catheter. Thirty minutes later, 60 mg/m2 cisplatin was
      administered intravenously over 1h. Subsequently, the same dose of droperidol was
      also injected epidurally every 6 h for 18 h. Postoperatively, the antiemetic
      effect was evaluated until 30 h after the first epidural droperidol. As a result,
      all patients expressed almost complete antiemesis until 25 h. After 26 h, some
      patients complained of mild emesis. No potential side effects, such as
      hypotension, consciousness disturbance, and extrapyramidal signs, were noticed.
      Therefore, the present pilot study implies that a sole epidural administration of
      droperidol remarkably suppresses cisplatin-induced emesis.

PMID- 9525021
TI  - Avoiding muscle cutting while extending McBurney's incision: a new surgical
      concept.
AB  - Extending a McBurney's muscle-splitting incision, to achieve a better exposure
      when performing a difficult appendectomy, by muscle cutting may be associated
      with an increase in patient morbidity. In a retrospective study we Verified two
      actual indications that call for wound extension. The first is to correct a
      malpositioned first incision that does not match an existing anatomical variation
      in the region of the appendix. The second is to achieve a wide surgical space to
      deal with complicated cases. For each of these two indications, we thus
      introduced a new technique that fulfills the real requirement without muscle
      cutting. For the first indication we used a double muscle-splitting incision,
      while for the second indication we combined the original muscle-splitting
      incision with a vertical incision of the posterior lamina of the anterior rectus
      sheath. The two techniques are herein presented and the results of their
      application in 126 cases are discussed.

PMID- 9525023
TI  - Evaluation of a transpelvic sling procedure with and without colposuspension for
      treatment of female dogs with refractory urethral sphincter mechanism
      incompetence.
AB  - OBJECTIVE: To evaluate a sling procedure using a polyester ribbon passed through
      the obturator foramen, around the urethra, and fixed outside the pelvis for the
      treatment of female dogs with refractory urethral sphincter mechanism
      incompetence (USMI). ANIMALS: 26 female dogs with USMI that had not improved with
      medical management. METHODS: All dogs underwent a transpelvic sling procedure,
      and in 13, with a radiographic diagnosis of a pelvic bladder, additional
      colposuspension was performed. Multichannel urethral pressure profilometry (UPP)
      and diuresis cystourethrometry (UCM) were performed in all dogs before and in
      seven dogs 2 to 14 months after surgery. Long-term results of surgery and medical
      therapy were determined. RESULTS: 13 dogs (50%), 6 of these without additional
      colposuspension, were continent after surgery and remained continent during a
      follow-up period of 12 to 36 months (mean, 19 months). Seven, three of which had
      colposuspension, had improved markedly. Four of these dogs became continent with
      additional medical therapy. Five dogs did not improve, and three of these were
      eventually euthanatized. In one dog, the sling was removed after 5 days because
      of persistent stranguria. Surgery and medical therapy together resulted in
      continence in 17 dogs (65%) during a follow-up period of 6 to 36 months (mean, 22
      months). Postoperative dysuria or stranguria occurred in six dogs, and four of
      these underwent a colposuspension procedure. Two dogs developed a fistula, 2 and
      3 years after surgery. Preoperatively, decreased urethral resistance was
      suggested by the findings of UPP and UCM in 25 dogs, and an abnormally high
      compliance was found in 3, detrusor instability in 2, and a low threshold
      pressure in 1 dog. There was no apparent correlation between these findings and
      the outcome of surgery. Urethral closure pressures measured after surgery were
      significantly increased but were still lower than the normal range in all dogs
      with persistent or recurrent incontinence. CONCLUSIONS: A transpelvic sling
      procedure, with or without additional colposuspension, can be useful in the
      management of dogs with refractory urinary incontinence. The procedure is not
      beneficial if it does not increase urethral pressure close to, or within, the
      normal range.

PMID- 9525022
TI  - Radiographic, densitometric, and biomechanical effects of recombinant canine
      somatotropin in an unstable ostectomy gap model of bone healing in dogs.
AB  - OBJECTIVE: To determine the effect of recombinant canine somatotropin (STH) on
      radiographic, densitometric, and biomechanical aspects of bone healing using an
      unstable ostectomy gap model. STUDY DESIGN: After an ostectomy of the midshaft
      radius, bone healing was evaluated over an 8-week period in control dogs (n = 4)
      and dogs receiving recombinant canine STH (n = 4). ANIMALS OR SAMPLE POPULATION:
      Eight sexually intact female Beagle dogs, 4 to 5 years old. METHODS: Bone healing
      was evaluated by qualitative and quantitative evaluation of serial radiographs
      every 2 weeks. Terminal dual-energy x-ray absorptiometry and three-point bending
      biomechanical testing were also performed. RESULTS: Dogs receiving STH had more
      advanced radiographic healing of ostectomy sites. Bone area, bone mineral
      content, and bone density were two to five times greater at the ostectomy sites
      of treated dogs. Ultimate load at failure and stiffness were three and five times
      greater in dogs receiving STH. CONCLUSIONS: Using the ostectomy gap model,
      recombinant canine STH enhanced the radiographic, densitometric, and
      biomechanical aspects of bone healing in dogs. CLINICAL RELEVANCE: Dogs at risk
      for delayed healing of fractures may benefit from treatment with recombinant
      canine STH.

PMID- 9525024
TI  - Correlation of clinical, radiographic, and surgical localization of
      intervertebral disc extrusion in small-breed dogs: a prospective study of 50
      cases.
AB  - OBJECTIVE: To compare prospectively clinical, radiographic, and surgical findings
      of intervertebral disc extrusion (IDE) localization in small-breed dogs and to
      determine the best means of lesion localization for the purpose of
      hemilaminectomy. STUDY DESIGN: Clinical, radiographic, and surgical findings of
      small-breed dogs with thoracolumbar IDE were prospectively compared for agreement
      on lesion localization. SAMPLE POPULATION: 50 small-breed dogs with IDE treated
      at the three participating veterinary hospitals were included in the study if no
      other confounding diseases were identified and if the owner gave permission for
      diagnostic tests and surgery. METHODS: Clinical and surgical findings were
      recorded by the surgeon assigned to the case. Radiographic studies were evaluated
      independently by two radiologists blinded as to the clinical and surgical
      findings. kappa values and 95% confidence intervals were calculated for agreement
      on lesion localization by clinical, radiographic, and surgical means and for
      agreement between radiologists. RESULTS: kappa values for agreement of lesion
      localization were as follows: clinical versus surgical, 0.595; radiologist A
      versus radiologist B, 0.81; radiologist A versus surgical findings, 0.60;
      radiologist B versus surgical findings, 0.71. Both radiologists' interpretation
      of IDE localization agreed with surgical localization in 60% of cases.
      CONCLUSIONS: Clinical lateralization of IDE was found to be the least reliable
      factor of those studied for determining on which side the hemilaminectomy should
      be performed. Results of this study differ from those of previous studies
      examining the reliability of myelography to localize the site of IDE accurately.
      The results of this study further suggest that surgery may not be an absolute
      standard for determination of the localization of IDE in small-breed dogs.
      CLINICAL RELEVANCE: Intervertebral disc extrusion in small-breed dogs frequently
      results in bilateral distribution of extruded material. Computed tomography or
      magnetic resonance imaging may be necessary to delineate completely the
      distribution of extruded disc material in IDE.

PMID- 9525025
TI  - Acute gastrointestinal disease in 27 New World camelids: clinical and surgical
      findings.
AB  - OBJECTIVE: To describe clinical and surgical findings from New World camelids
      with acute gastrointestinal disease. STUDY DESIGN: Retrospective study. ANIMAL
      POPULATION: 20 llamas and 7 alpacas. METHODS: Camelids were grouped based on
      surgical lesions. Clinical and surgical findings were compared between groups and
      between surviving and nonsurviving camelids. RESULTS: Twelve of 27 initial
      celiotomies and 3 of 4 repeat celiotomies were successful. Death occurred from
      euthanasia during surgery (nine camelids), peritonitis or sepsis (five),
      aspiration pneumonia (one), and respiratory distress (one). Survival was lowest
      after celiotomy for proximal obstruction (3 of 10 camelids), ruptured viscus (0
      of 4), and necrotizing enteritis (0 of 2) and highest after celiotomy for distal
      obstruction (10 of 13) and septic peritonitis without ruptured viscus (2 of 2).
      Before surgery, camelids with proximal obstruction had significantly lower (P <
      .05) serum chloride concentrations (median, 97 mEq/L) than those with distal
      obstruction (median, 109 mEq/L) or ruptured viscus (median, 117 mEq/L). Serum
      bicarbonate concentration also was highest (median, 34.6 mEq/L) and often greater
      than 28 mEq/L in camelids with proximal obstruction. Camelids with distal
      obstruction had significantly lower (P < .05) nucleated cell counts in peritoneal
      fluid (median, 700 cells/microL) than those with ruptured viscus (median, 20,600
      cells/microL) or septic peritonitis (median, 88,300 cells/microL). CONCLUSIONS:
      Camelids with proximal obstruction often had hypochloremic metabolic alkalosis.
      Camelids with distal obstruction had less metabolic derangement and tissue
      compromise and a higher survival rate. CLINICAL RELEVANCE: Awareness of the
      characteristics of the various types of acute gastrointestinal disease in
      camelids will augment veterinarians' ability to diagnose and treat these
      disorders.

PMID- 9525026
TI  - Evaluation of postoperative peritoneal lavage in standing horses for prevention
      of experimentally induced abdominal adhesions.
AB  - OBJECTIVE: To evaluate the postoperative use of peritoneal lavage for prevention
      of experimentally induced intraabdominal adhesions in horses. STUDY DESIGN: Areas
      of serosal abrasion were created on the jejunum of 12 horses. Postoperatively,
      six horses had peritoneal lavage, and six horses did not (controls). The number
      of adhesions was determined at necropsy 2 weeks after surgery. ANIMALS OR SAMPLE
      POPULATION: 12 horses. METHODS: Five sites of jejunal serosal abrasion were
      created in each horse. A 32 French thoracic catheter was placed into the right
      ventral aspect of the abdomen before closure of the abdominal incision. Treated
      horses had abdominal lavage with 10 L of lactated Ringer's solution on four
      occasions, then catheters were removed from all horses 34 hours after celiotomy.
      Horses were necropsied at 2 weeks to quantify the number of intraabdominal
      adhesions. RESULTS: All control horses and one treated horse developed
      intraabdominal adhesions. The number of adhesions was significantly less (P <
      .0293) in treated horses. No adverse inflammatory reactions appeared to be
      associated with repeated peritoneal lavage using lactated Ringer's solution or
      use of an abdominal drain. CONCLUSIONS: Peritoneal lavage reduced the frequency
      of intraabdominal adhesions. CLINICAL RELEVANCE: When postoperative adhesions are
      likely to develop, postoperative peritoneal lavage may decrease the frequency of
      adhesion formation.

PMID- 9525027
TI  - A modified technique for extensive large colon resection and anastomosis in
      horses.
AB  - OBJECTIVE: To describe an alternative technique for large colon resection and
      anastomosis in horses. STUDY DESIGN: Retrospective study of clinical patients.
      ANIMAL POPULATION: 37 horses that had ventral midline celiotomies between July 1,
      1990, and July 1, 1994. METHODS: Large colon resection and anastomosis was
      performed using a modification of previously described techniques. Modifications
      include mesocolon ligation with a stapling device and an end-to-end apposition of
      the right ventral and right dorsal colon. RESULTS: Twenty-one of the 37 horses
      were discharged from the hospital without complications. Two horses were
      euthanatized immediately after recovery from anesthesia because of hindlimb
      fracture. Fourteen horses were euthanatized in the initial postoperative period
      because of persistent endotoxemia and abdominal pain. CONCLUSIONS: The described
      technique is a safe, reliable method for large colon resection and anastomosis in
      horses. CLINICAL RELEVANCE: The described technique is fairly simple to perform
      and requires less surgical time compared with other techniques.

PMID- 9525028
TI  - Effect of omentectomy on adhesion formation in horses.
AB  - OBJECTIVE: To determine if omentectomy would decrease the frequency of
      postoperative intraabdominal adhesions. STUDY DESIGN: Retrospective study.
      ANIMALS OR SAMPLE POPULATION: 44 horses that had either two ventral median
      celiotomies or a ventral median celiotomy and a necropsy more than 4 days later;
      19 of these horses had their omentum removed at the initial surgery. METHODS:
      Data retrieved from the records included location and type of intraabdominal
      adhesions; location of the surgical lesion; relationship of adhesions to the
      surgical lesion; surgical procedures; duration of initial surgery; time interval
      between procedures; age, gender, and breed of the horse; and clinical outcome.
      Fisher's exact test was used to evaluate the association between categorical
      explanatory and outcome variables. The effect of potential risk factors on the
      incidence rate of adhesion formation was estimated using a proportional hazards
      regression model. RESULTS: Of 25 horses in the nonomentectomy group, 15 (60%) had
      postoperative adhesions that resulted in the need for a second surgical
      intervention, whereas of 19 horses that had omentectomy initially, only 4 (21%)
      had postoperative adhesions that required a second procedure. Rate of adhesion
      formation was higher in horses that did not have omentectomy initially (incidence
      ratio rate [IRR], 0.46; 90% confidence interval [CI], 0.18 to 1.19). At initial
      surgery, 24 horses had a small intestinal lesion, and 20 horses had a large
      intestinal lesion. Fifteen horses (63%) with small intestinal lesions
      subsequently developed adhesions compared with four horses (20%) with an initial
      large intestinal lesion (P = .006). At the second procedure, small intestine
      lesions were identified in 32 horses and large intestine lesions in 12 horses (1
      horse had both small and large intestine lesions), and 1 horse had a gastric
      lesion. Adhesions were identified as the cause of colic signs in 19 (61%) horses
      with small intestinal lesions and in none of the horses with large intestine
      lesions. The frequency of adhesion development leading to colic associated with
      only the small intestine at the second surgery or necropsy was significantly
      greater (P = .001) than the frequency only in the large intestine. CONCLUSIONS:
      Omentectomy reduced the rate of postoperative adhesion formation. Adhesions are
      more likely to occur after small intestinal surgery and if they do occur likely
      involve the small intestine. CLINICAL RELEVANCE: Omentectomy is a safe procedure
      and should be considered prophylactically for reduction of adhesion formation
      after abdominal surgery in horses.

PMID- 9525029
TI  - Ventral abdominal approach for laparoscopic cryptorchidectomy in horses.
AB  - OBJECTIVE: To report a ventral abdominal approach and a ligating loop technique
      for laparoscopic cryptorchidectomy in horses. STUDY DESIGN: Prospective. SAMPLE
      POPULATION: Six horses, aged 1 to 5 years, with retained testes. METHODS: One
      laparoscopic portal and three to four instrument portals were used for ventral
      abdominal laparoscopic cryptorchidectomy. Laparoscopic instruments were used to
      maneuver and secure the testis through a ligating loop (modified Roeder knot)
      that was secured from outside the abdominal cavity. Only minimal enlargement of
      one instrument portal was used to remove the testicle. RESULTS: Three horses were
      bilateral cryptorchids, and three were unilateral (left side, two; right side,
      one) cryptorchids. Operative time, defined as the time from laparoscope insertion
      to removal, ranged from 20 to 25 minutes for unilateral cryptorchids and from 40
      to 50 minutes for bilateral cryptorchids. CONCLUSIONS: The reported technique
      allowed decreased tension on the tissues during ligation and removal of the
      testis from the peritoneal cavity. Improved observation of the abdominal cavity,
      ligation security, shortened patient confinement time, and minimally invasive
      technique are all considered to be benefits of laparoscopic cryptorchidectomy.
      CLINICAL RELEVANCE: Direct observation of retained testes and intraabdominal
      castration are distinct advantages of the use of laparoscopy in horses that have
      had previous unsuccessful surgical attempts, horses with unknown histories that
      have retained testicular tissue, or bilateral abdominal cryptorchids.

PMID- 9525030
TI  - In vitro pullout strength of screws inserted in adult equine third metacarpal
      bone after overdrilling a 4.5-mm threaded insertion hole.
AB  - OBJECTIVE: To determine and compare the in vitro pullout strength of 5.5-mm
      cortical versus 6.5-mm cancellous bone screws inserted in the diaphysis and
      metaphysis of adult equine third metacarpal (MCIII) bones, in threaded 4.5-mm
      cortical bone screw insertion holes that were then overdrilled with a 4.5-mm
      drill bit to provide information relevant to the selection of a replacement screw
      if a 4.5-mm cortical screw is stripped. STUDY DESIGN: In vitro pullout tests of
      5.5-mm cortical and 6.5-mm cancellous screws in equine MCIII bones. SAMPLE
      POPULATION: Two independent cadaver studies each consisting of 14 adult equine
      MCIII bones. METHODS: Two 4.5-mm cortical screws were placed either in the
      middiaphysis (study 1) or distal metaphysis (study 2) of MCIII bones. The holes
      were then overdrilled with a 4.5-mm drill bit and had either a 5.5-mm cortical or
      a 6.5-mm cancellous screw inserted; screw pullout tests were performed at a rate
      of 0.04 mm/second until screw or bone failure occurred. RESULTS: In diaphyseal
      bone, the screws failed in all tests. Tensile breaking strength for 5.5-mm
      cortical screws (997.5 +/- 49.3 kg) and 6.5-mm cancellous screws (931.6 +/- 19.5
      kg) was not significantly different. In metaphyseal bone, the bone failed in all
      tests. The holding power for 6.5-mm cancellous screws (39.1 +/- 4.9 kg/mm) was
      significantly greater than 5.5-mm cortical screws (23.5 +/- 3.5 kg/mm) in the
      metaphysis. There was no difference in the tensile breaking strength of screws in
      the diaphysis between proximal and distal screw holes; however, the holding power
      was significantly greater in the distal, compared with the proximal, metaphyseal
      holes. CONCLUSIONS: Although tensile breaking strength was not different between
      5.5-mm cortical and 6.5-mm cancellous screws in middiaphyseal cortical bone,
      holding power of 6.5-mm cancellous screws was greater than 5.5-mm cortical screws
      in metaphyseal bone of adult horses. CLINICAL RELEVANCE: If a 4.5-mm cortical
      bone screw strips in MCIII diaphyseal bone of adult horses, either a 5.5-mm
      cortical or 6.5-mm cancellous screw, however, would have equivalent pullout
      strengths. A 6.5-mm cancellous screw, however, would provide greater holding
      power than a 5.5-mm cortical screw in metaphyseal bone.

PMID- 9525031
TI  - Tenoscopic anatomy of the equine carpal flexor synovial sheath.
AB  - OBJECTIVE: To describe the tenoscopic anatomy of the carpal sheath of the flexor
      tendons (carpal sheath) viewed from a lateral approach. STUDY DESIGN: Tenoscopic
      observation of structures within the carpal sheath subsequently confirmed by
      dissection. ANIMALS OR SAMPLE POPULATION: 12 equine cadaveric forelimbs. METHODS:
      The limbs were positioned lateral side up with the carpus slightly flexed. After
      distention of the carpal sheath, a portal for the arthroscope was made
      approximately 3 cm proximal to the distal radial physis and 2.5 cm caudal to the
      radius between the tendons of the ulnaris lateralis and lateral digital extensor
      muscles. RESULTS: A lateral tenoscopic approach was adequate to identify all
      structures within the carpal sheath. From proximal to distal, structures
      identified using this approach were the radial head of the deep digital flexor
      muscle, accessory ligament of the tendon of the superficial digital flexor
      muscle, distal radial physis, tendons of the superficial and deep digital flexor
      muscles, accessory carpal bone, antebrachiocarpal and middle carpal joints, and
      vincula of the tendon of the deep digital flexor muscle. CONCLUSIONS: A lateral
      tenoscopic approach offered an easy, repeatable entry into the carpal sheath and
      allowed good observation of all structures within the sheath except for the
      medial borders of the tendons of the deep and superficial digital flexor muscles.
      CLINICAL RELEVANCE: Applications of a lateral tenoscopic approach to the carpal
      sheath include diagnostic procedures, lavage and synovial resection for septic
      tenosynovitis, desmotomy of the accessory ligament of the tendon of the
      superficial digital flexor muscle for flexural deformity or tendinitis, and
      removal of osteochondromas from the distal radial metaphysis.

PMID- 9525032
TI  - Comparison of plasma fentanyl concentrations by using three transdermal fentanyl
      patch sizes in dogs.
AB  - OBJECTIVE: To compare plasma fentanyl concentrations attained after the
      application of three transdermal fentanyl patch sizes (50, 75, and 100
      micrograms/hour) in dogs. DESIGN: Repeated Latin square controlled study.
      ANIMALS: Six intact, mixed-breed adult dogs (2 males, 4 females) weighing 19.9 +/
      3.4 kg. METHODS: Each dog was randomly assigned to receive each of three
      treatments: 50 (P50), 75 (P75), or 100 (P100) micrograms/hour transdermal
      patches. Patches were left in place for 72 hours. Jugular venous blood was
      collected at 1, 2, 4, 8, 12, 24, 36, 48, 60, and 72 hours after patch application
      and for 1, 2, 4, 8, and 12 hours after patch removal. Plasma fentanyl
      concentrations were measured using a radioimmunoassay technique. After a 96-hour
      washout period, each dog was moved to another treatment group and received a
      different patch size. RESULTS: The following results were obtained (mean +/- SD):
      average plasma fentanyl concentration from 24 to 72 hours, 0.7 +/- 0.2 ng/mL
      (P50), 1.4 +/- 0.5 ng/mL (P75), 1.2 +/- 0.5 ng/mL (P100); the total area under
      the concentration versus time curve (0 hours to infinity), 46 +/- 12.2 ng/h/mL
      (P50), 101.2 +/- 41.4 ng/h/mL (P75), 80.4 +/- 38.3 ng/h/mL (P100); and the
      apparent elimination half-life, 3.6 +/- 1.2 hours (P50), 3.4 +/- 2.7 hours (P75),
      and 2.5 +/- 2.0 hours (P100). There was a high degree of variability in plasma
      fentanyl concentrations achieved. Plasma fentanyl concentrations declined rapidly
      after patch removal. CONCLUSIONS: The attainment of steady-state plasma
      concentrations takes up to 24 hours, and there is a great deal of variability in
      the final concentrations reached in different individuals. In this study, the 100
      micrograms/hour patches did not provide statistically increased plasma
      concentrations when compared with the 50 micrograms/hour patches. CLINICAL
      RELEVANCE: Because of the interindividual and intraindividual variation in plasma
      fentanyl concentrations, patches should be applied 24 hours before the
      anticipated time that analgesia will be required. Adequacy of analgesia and
      potentially deleterious side effects, such as sedation and respiratory
      depression, should be monitored while the patches are in place. Skin reactions
      may occur, and the patches should be removed if such skin irritation is seen.
      After the patch is removed, it is expected that analgesia will wane rapidly
      because of the brief elimination half-life.

PMID- 9525033
TI  - Mechanical significance of obliquely striated architecture in nematode muscle.
AB  - In certain invertebrate muscles, adjacent narrow columns of sarcomeres are
      displaced along the fiber axis, providing an obliquely striated myofilament
      pattern in certain section planes. Although this architecture is described in
      many phyla and has been the subject of much discussion (1-12), its mechanical
      significance has yet to be resolved. In nematodes, where ultrastructural details
      of the obliquely striated muscle have long been known (12-19), another unique and
      prominent feature is the attachment of every sarcomere to the plasmalemma and
      basal lamina via dense bodies (Z-disc analogs). Unfortunately, the importance of
      this feature to the transmission of the contractile force to the cuticle is not
      understood outside the Caenorhabditis elegans literature: it was overlooked in
      recent reviews covering obliquely striated muscle (9-11). Here we consider
      transmission of force and oblique striation together. We compare the contractile
      architecture in C. elegans with that in the more complex muscle type of larger
      nematodes. Both types are designed to transmit the force of contraction laterally
      to the cuticle rather than longitudinally to the muscle ends. In the second type,
      folding of the contractile structure around an inward extension of the basal
      lamina enables a higher number of sarcomeres to be linked to cuticle per unit
      length. We suggest that the mechanical significance of the oblique arrangement of
      sarcomeres in both types is that it distributes the force application sites of
      the sarcomeres more evenly over the basal lamina and cuticle. With this muscle
      architecture, smooth bending of the nematode body tube would be possible, and
      kinking would be prevented.

PMID- 9525034
TI  - Hebbian learning in parallel and modular memories.
AB  - Many cognitive and sensorimotor functions in the brain involve parallel and
      modular memory subsystems that are adapted by activity-dependent Hebbian synaptic
      plasticity. This is in contrast to the multilayer perceptron model of supervised
      learning where sensory information is presumed to be integrated by a common pool
      of hidden units through backpropagation learning. Here we show that Hebbian
      learning in parallel and modular memories is more advantageous than
      backpropagation learning in lumped memories in two respects: it is
      computationally much more efficient and structurally much simpler to implement
      with biological neurons. Accordingly, we propose a more biologically relevant
      neural network model, called a tree-like perceptron, which is a simple
      modification of the multilayer perceptron model to account for the general neural
      architecture, neuronal specificity, and synaptic learning rule in the brain. The
      model features a parallel and modular architecture in which adaptation of the
      input-to-hidden connection follows either a Hebbian or anti-Hebbian rule
      depending on whether the hidden units are excitatory or inhibitory, respectively.
      The proposed parallel and modular architecture and implicit interplay between the
      types of synaptic plasticity and neuronal specificity are exhibited by some
      neocortical and cerebellar systems.

PMID- 9525035
TI  - A dynamic neural network with temporal coding and functional connectivity.
AB  - A neural network model capable of altering its pattern classifying properties by
      program input is proposed. Here the "program input" is another source of input
      besides the pattern input. Unlike most neural network models, this model runs as
      a deterministic point process of spikes in continuous time; connections among
      neurons have finite delays, which are set randomly according to a normal
      distribution. Furthermore, this model utilizes functional connectivity which is
      dynamic connectivity among neurons peculiar to temporal-coding neural networks
      with short neuronal decay time constants. Computer simulation of the proposed
      network has been performed, and the results are considered in light of
      experimental results shown recently for correlated firings of neurons.

PMID- 9525036
TI  - A cross-interval spike train analysis: the correlation between spike generation
      and temporal integration of doublets.
AB  - A stochastic spike train analysis technique is introduced to reveal the
      correlation between the firing of the next spike and the temporal integration
      period of two consecutive spikes (i.e., a doublet). Statistics of spike firing
      times between neurons are established to obtain the conditional probability of
      spike firing in relation to the integration period. The existence of a temporal
      integration period is deduced from the time interval between two consecutive
      spikes fired in a reference neuron as a precondition to the generation of the
      next spike in a compared neuron. This analysis can show whether the coupled spike
      firing in the compared neuron is correlated with the last or the second-to-last
      spike in the reference neuron. Analysis of simulated and experimentally recorded
      biological spike trains shows that the effects of excitatory and inhibitory
      temporal integration are extracted by this method without relying on any
      subthreshold potential recordings. The analysis also shows that, with temporal
      integration, a neuron driven by random firing patterns can produce fairly regular
      firing patterns under appropriate conditions. This regularity in firing can be
      enhanced by temporal integration of spikes in a chain of polysynaptically
      connected neurons. The bandpass filtering of spike firings by temporal
      integration is discussed. The results also reveal that signal transmission delays
      may be attributed not just to conduction and synaptic delays, but also to the
      delay time needed for temporal integration.

PMID- 9525037
TI  - Modeling perceptual learning: difficulties and how they can be overcome.
AB  - We investigated the roles of feedback and attention in training a vernier
      discrimination task as an example of perceptual learning. Human learning even of
      simple stimuli, such as verniers, relies on more complex mechanisms than
      previously expected--ruling out simple neural network models. These findings are
      not just an empirical oddity but are evidence that present models fail to reflect
      some important characteristics of the learning process. We will list some of the
      problems of neural networks and develop a new model that solves them by
      incorporating top-down mechanisms. Contrary to neural networks, in our model
      learning is not driven by the set of stimuli only. Internal estimations of
      performance and knowledge about the task are also incorporated. Our model implies
      that under certain conditions the detectability of only some of the stimuli is
      enhanced while the overall improvement of performance is attributed to a change
      of decision criteria. An experiment confirms this prediction.

PMID- 9525038
TI  - A kinematic theory of rapid human movements: Part III. Kinetic outcomes.
AB  - This paper describes the kinematic and kinetic properties of simple rapid
      movements using a single and unique framework based on a delta-lognormal law
      (Plamondon 1993a,b, 1995a,b). Predictions concerning isotonic measurements are
      made using the properties of acceleration profiles, as described by the first
      time derivative of the delta-lognormal law. Predictions dealing with isometric
      measurements are directly analyzed using the delta-lognormal law, after
      demonstrating the experimental equivalence between isometric forces and virtual
      velocity profiles. The theory is also used to make statistical predictions about
      the variability of numerous kinematic and kinetic variables. The overall approach
      can be viewed as if, at some level of representation, the central nervous system
      were planning, executing and evaluating simple rapid movements in terms of
      momentum and energy instead of forces. The unifying perspective provided by the
      theory constitutes a powerful tool with which to study and analyze movements
      under numerous experimental conditions, using a single analytical law.

PMID- 9525039
TI  - A large-scale model of some spinal reflex circuits.
AB  - This paper reports the development of a large-scale model of some spinal reflex
      circuitry, useful for studying the dynamic interactions among neuronal
      populations during simple behaviors. The included populations and properties of
      the neurons and terminals were derived from the literature, mainly on cat spinal
      cord. The model was conceived as a symmetrical controller of a pair of
      antagonistic muscles, within the behavioral domain of the stretch and Golgi
      tendon-organ reflexes, and was scaled to include realistic numbers of
      motoneurons. Inputs to the model were fiber populations providing random synaptic
      drive to some of the populations and sensory stimuli appropriate for the
      reflexes. The resulting model contained roughly 2300 neurons in six pairs of
      populations. The total number of connections in the model was about 600,000, and
      individual postsynaptic potentials were small (0.1-0.6 mV). Model responses were
      calibrated by examination of their ability to reproduce known aspects of the
      reflexes. Published algorithms were used to construct the environment, which is
      easily expandable, in terms of membrane channels, neuronal geometry, and synaptic
      properties. The system was built to combine a system-level perspective of spinal
      circuitry with the single-unit perspective common in electrophysiological
      investigation. It provides a computational tool for system-level investigations
      of spinal cord similar to the tools available at the level of membrane currents.

PMID- 9525040
TI  - Determining the degree of chaos from analysis of ISI time series in the nervous
      system: a comparison between correlation dimension and nonlinear forecasting
      methods.
AB  - Two different chaotic time series analysis methods--the correlation dimension and
      nonlinear forecasting--are introduced and then used to process the interspike
      intervals (ISI) of the action potential trains propagated along a single nerve
      fiber of the anesthetized rat. From the results, the conclusion is drawn that
      compared with the correlation dimension, nonlinear forecasting is more efficient
      and robust for chaotic ISI time series analysis in a noisy environment. Moreover,
      the evolution of the correlation coefficient curves calculated from nonlinear
      forecasting can qualitatively give a better reflection of the unpredictability of
      the system's future behavior and is in good agreement with the values of the
      largest Lyapunov exponent that quantitatively measures the degree of chaos.

PMID- 9525041
TI  - In memoriam Cyril Andrew Ponnamperuma 1923-1994.

PMID- 9525042
TI  - Cyril Ponnamperuma and the origin of life: a bibliography.

PMID- 9525043
TI  - First steps in eukaryogenesis: physical phenomena in the origin and evolution of
      chromosome structure.
AB  - Our present understanding of the origin and evolution of chromosomes differs
      considerably from current understanding of the origin and evolution of the cell
      itself. Chromosome origins have been less prominent in research, as the emphasis
      has not shifted so far appreciably from the phenomenon of primeval nucleic acid
      encapsulation to that of the origin of gene organization, expression, and
      regulation. In this work we discuss some reasons why preliminary steps in this
      direction are being taken. We have been led to examine properties that have
      contributed to raise the ancestral prokaryotic programmes to a level where we can
      appreciate in eukaryotes a clear departure from earlier themes in the evolution
      of the cell from the last common ancestor. We shift our point of view from
      evolution of cell morphology to the point of view of the genes. In particular, we
      focus attention on possible physical bases for the way transmission of
      information has evolved in eukaryotes, namely, the inactivation of whole
      chromosomes. The special case of the inactivation of the X chromosome in mammals
      is discussed, paying particular attention to the physical process of the spread
      of X inactivation in monotremes (platypus and echidna). When experimental data is
      unavailable some theoretical analysis is possible based on the idea that in
      certain cases collective phenomena in genetics, rather than chemical detail, are
      better correlates of complex chemical processes.

PMID- 9525044
TI  - Atmospheric metal pollution (Cr, Cu, Fe, Mn, Ni, Pb and Zn) in Oporto city
      derived from results for low-volume aerosol samplers and for the moss Sphagnum
      auriculatum bioindicator.
AB  - A low-volume aerosol sampler with filters and bags of Sphagnum auriculatum were
      exposed, in parallel, to the atmosphere of Oporto city for approx. 2 months in
      1994, during a dry weather period. The levels of Cr, Cu, Fe, Mn, Ni, Pb and Zn in
      the moss (weekly samples) and in the filters (daily samples) were determined by
      atomic absorption spectrophotometry and the results were compared. For all the
      heavy metals, the rate of metal uptake by moss was significantly correlated with
      the metal concentration in atmospheric aerosols. The results indicated that moss
      bags of S. auriculatum can provide a quantitative estimation of the concentration
      of different heavy metals in urban atmospheres, when specific calibration by
      mechanic monitoring, at the same sampling point, is performed during a first
      stage of biomonitoring. The mean aerosol metal concentrations found in the Oporto
      atmosphere were similar to those observed in other urban atmospheres in different
      countries. The relative order of the mean metal concentrations was Fe (1.8
      micrograms/m3) > Zn > Pb > Cu > Cr > Mn > Ni (20 ng/m3). The aerosol Pb levels
      were monitored at different sampling points over various periods of time between
      1991 and 1997. The mean Pb levels were < or = 0.5 microgram/m3 and approximately
      constant at each sample point up to January 1996. After that date it decreased by
      approx. 50%, in consequence of the reduction of the Pb concentration in leaded
      gasoline.

PMID- 9525045
TI  - Copper (II) complexation in northern California rice field waters: an
      investigation using differential pulse anodic and cathodic stripping voltammetry.
AB  - Differential pulse anodic stripping voltammetry (DPASV) and competitive ligand
      equilibration-cathodic stripping voltammetry (CLE-CSV) demonstrated that > or =
      99% of the dissolved copper in five rice field waters, one river water and a
      catchment basin water collected at sites in northern California is complexed by
      natural organic matter. Concentrations of natural copper complexing ligands (CL)
      ranged from 81 to 426 nM determined by CLE-CSV using the competitive ligand 8
      hydroxyquinoline and from 156 to 1374 nM using DPASV. Experimental values for
      conditional stability constants (with respect to free Cu2+) of natural copper
      organic ligand complexes (log K'CuL) fell in the range 10.2-11.2 using DPASV and
      11.1-11.5 using CLE-CSV. DPASV analyses revealed evidence of organic matter
      adsorption to the electrode surface at low dissolved organic carbon (DOC)
      concentrations (i.e. 200 micrograms l-1 DOC for a 10-min deposition period), for
      some but not all water samples. Examination of lyophilized, filtered rice field
      water using scanning electron microscopy (SEM) and pyrolysis gas chromatography
      mass spectrometry (pyr-GC/MS) did not reveal differences that could be associated
      with surface active material. Uncomplexed copper accounts for only minor amounts
      of total copper in rice field waters and natural ligands are expected to
      influence its effectiveness as an agrochemical.

PMID- 9525046
TI  - Trace metals in oysters and sediments of Botany Bay, Sydney.
AB  - Trace metal concentrations (Pb, Cd, Cu and Zn) in Sydney rock oysters (Sacostera
      commercialis) and sediments (< 53 microns fraction) were determined for six sites
      in the northern regions of Botany Bay. Levels for lead, cadmium, copper and zinc
      in oysters ranged (in microgram g-1) from 1.38 to 15.3, 1.81 to 16.3, 56.1 to 212
      and 1806 to 2902, respectively. In sediments, levels ranged (in microgram g-1)
      from 599 to 4081, 3.57 to 91.0, 191 to 1113 and 227 to 1472, respectively. Such
      values indicated high levels of contamination, especially in the sediments.
      Indeed, high proportions of the samples displayed metal concentrations that
      exceeded the prescribed limits for oysters and sediments. No significant
      correlations in metal concentrations were found between oysters and sediments,
      suggesting that changes in the sediment metal loading are not solely influencing
      the levels of bioavailable metal. The results supported the conclusion that
      different rates and mechanisms of metal accumulation are taking place in the two
      types of samples. Variability between sites was high, particularly for oysters.
      Multidimensional scaling identified that the Cooks River (site 3) and La Perouse
      (site 6) sites were most dissimilar, both to each other as well as to the other
      four sites. This was a reflection of high contamination in the Cooks River and
      the generally low levels in the La Perouse reference sample. The configuration
      was mainly influenced by the sediment parameters, rather than the oyster metal
      concentrations, indicating the sediment data were better for identifying site
      similarities. These ordinations provide evidence of the usefulness of
      multidimensional scaling in elucidating the physico-chemical variability of the
      sampling sites.

PMID- 9525048
TI  - [Transesophageal echocardiography in the management of patients with atrial
      fibrillation].
AB  - The review evaluates the contribution of transoesophageal echocardiography as to
      the improvement of management of patients with atrial fibrillation. It emphasises
      the severity of fibrillation arrhythmia regarding the haemodynamic complications,
      but especially those arising from embolism causing significant morbidity and
      mortality, especially in the aged patients with organic heart diseases. An
      essential improvement in the imaging of the left atrium, but especially of its
      auricle has enabled a significant progress in the conception of the origin of
      thromboembolic complications after cardioversion of atrial fibrillation. The
      detection of thrombi in the left atrial auricle which had until now been
      impossible, enabled to postpone the patients, by use of transoesophageal
      echocardiography, for the considered cardioversion, thus reducing the risk of
      thromboembolism. On the other hand, the transoesophageal examination of the left
      atrial auricle by use of two-dimensional and doppler echocardiographies has
      enabled to judge the function of the left atrial auricle not only from the
      anatomical aspect, but also from that of pathophysiology. This fact enabled to
      stratify the patients at higher risk of thromboembolism, or vice versa, to select
      patients appropriate for the planned cardioversion of fibrillation arrhythmia,
      even if this state has been relatively prolonged. The current knowledge and
      experience are encouraging and it can be anticipated that within the course of a
      short period, the transoesophageal echocardiography will play an important role
      in the management of patients with atrial fibrillation. (Tab. 1, Fig. 3, Ref. 40)

PMID- 9525047
TI  - Correlation between urinary 1-hydroxypyrene and ambient air pyrene measured with
      an inhalable aerosol sampler and a total dust sampler in an electrode paste
      plant.
AB  - The aim of this study was to investigate whether the use of an inhalable aerosol
      sampler would improve the correlation between urinary 1-hydroxypyrene and
      occupational pyrene exposure compared to measurements with a total dust sampler
      in an electrode paste plant. PAHs were collected on a filter and adsorbent by a
      37-mm closed-face total aerosol sampler and an open-face sampler for inhalable
      aerosol from the Institute of Occupational Medicine (IOM). 1-Hydroxypyrene in pre
      and post-shift urine samples was quantitated by high performance liquid
      chromatography (HPLC). In this study, the use of the IOM sampler resulted in
      approximately four times higher concentrations of particulate PAH and pyrene than
      the total dust sampler. The correlation between pyrene levels measured with the
      two samplers was good with a correlation coefficient of 0.83. The correlation
      between workplace air pyrene and 1-hydroxypyrene in post-shift urine was poor (r
      = -0.12), but a small non-significant improvement was found with the IOM sampler
      (r = 0.11). In this factory the use of an inhalable aerosol sampler had only
      marginal effect on the correlation between 1-hydroxypyrene in urine and breathing
      zone pyrene. These results indicate that skin exposure is an important route of
      PAH uptake in this plant.

PMID- 9525049
TI  - [Diagnostic and therapeutic potential of transesophageal cardiac pacing in the
      management of patients with arrhythmias].
AB  - BACKGROUND: Transoesophageal cardiostimulation is a semiinvasive method of
      stimulation of atrii enabling the performance of the programmed atrial
      stimulation without the inevitability of an invasive vascular approach. This
      method was used in 124 patients with the following indication spectrum.
      Diagnostic indications: total 82%, paroxysmal supraventricular tachycardia (SVT),
      and WPW sy-22%, tachycardia with wide QRS-complex-8%. SSS syndrome and
      bradycardia-20%, sycopes and collapses with unclear etiology-13%, palpitations
      11%, control of antiarrhythmic therapy-4%, and other states-6%. Therapeutic
      indications: total-18%, versions of paroxysmal SVT and flutter of atrii. RESULTS:
      The patients with SVT were assumed to develop the arrhythmogenic mechanism--AV
      nodal re-entry tachycardia in 80%, orthodrome AV-re-entry tachycardia in 30%, and
      flutter of atrii in 20%. All patients with WPW-syndrome were stratified by the
      use of this method. The origin of this state from ventricular arrhythmia was
      verified in 40% of patients with tachycardia with a wide QRS complex. In
      coincidence with other indications, the diagnostic benefit of transoesophageal
      cardiostimulation was evaluated as follows: syncopes-68%, palpitations-64%,
      syndrome SSS and bradycardia-48%. The therapeutic indication of SVT version and
      flutter of atrii, was totally successful in 40%, partly successful in 45% and
      unsuccessful in 15% of patients. CONCLUSION: Transoesophageal cardiostimulation
      has contributed to the assessment of the diagnosis in 69% of patients and has
      acutely managed arrhythmia in 85% of cases. According to our experience, this
      method is effective in the initial management of patients with arrhythmia. Its
      low technical and economic demands make its wider utilisation appropriate in
      clinical practice of internal medicine. (Tab. 4, Fig. 9, Ref. 22).

PMID- 9525050
TI  - [Proarrhythmia--a paradox in clinical cardiology].
AB  - On the basis of both literature data and our own experience, the review analyzes
      the problem of proarrhythmia. The origin of proarrhythmia is determined by: left
      ventricular function, coronary bloodflow, autonomous nervous system tonus, the
      presence of hidden lesions of the conductive system of the heart or the presence
      of accessory tracts, antiarrhythmic therapy or other therapy with cardiotropic
      preparations and the state of the internal environment. Each antiarrhythmic drug
      can evoke proarrhythmia. Regarding the therapy of current proarrhythmia, the
      competitive preference is ascribed to those antiarrhythmic drugs which are
      quickly eliminated. Regarding both the antiarrhythmic therapy and the possible
      occurrence of proarrhythmia in patients with ichaemic heart disease, the
      administration of Beta-blockers seems to be mostly prospective. (Fig. 3, Ref.
      11).

PMID- 9525051
TI  - [Arrhythmogenic right ventricular dysplasia].
AB  - Arrhythmogenic dysplasia of the right ventricle as a nosological entity was
      described relatively recently. However, at present, it is gradually being
      diagnosed more frequently. The authors describe the typical clinical picture of
      this disease in one of several patients with this disease, who were hospitalised
      at SUSCH. The authors describe the diagnostical value of individual findings.
      They indicate the importance of knowledge of individual diagnostical criteria in
      order to be able to recognize this disease and distinguish it from idiopathic
      ventricular tachycardia, the prognosis of which is generally better and also the
      therapeutical approach less aggressive. (Fig. 6, Ref. 29).

PMID- 9525052
TI  - [Dual-chamber rate-regulated cardiac pacing is aiming toward automatic
      pacemakers].
AB  - DDDR cardiac pacemakers meet the demand of the two main goals of modern cardiac
      pacing enauring both the synchronization of atriums and ventricles and the
      frequency response to physical exercise. In this way they simulate the normal
      heart rhythm behaviour best of all pacemakers in use. Since 1992 through 1995 the
      DDDR pacemakers were implanted in 27 patients aged 20-79 (mean 59.9) years in our
      pacemaker centre. The follow-up period has amounted to 46 months. 26 patients
      suffered from advanced sinus syndrome with the chronotropic incompetence and with
      the atrioventricular block, the remaining young man was given the pacemaker
      because of congenital atrioventricular block. In one patient epicardial leads
      implanted by thoracotomy have been used. After the wound had healed and the pulse
      energy had been reduced, the pacemaker bearers underwent the stepwise symptoms
      limited bicycle or treadmill stress test. During the follow-up the incidence of
      particular complications was assessed. In comparison with the DDD mode without
      the sensor, the DDDR pacemakers exhibiting the rate adaptation did improve the
      working capacity in particular patients in the stress test. (Tab. 1, Fig. 5, Ref.
      16).

PMID- 9525053
TI  - [Treatment of paroxysmal ventricular tachycardia].
AB  - The authors present a retrospective evaluation of the risk stratification and
      therapy of 53 patients with ventricular tachycardia. They present the
      diagnostical algorithm used for the detection of risk of sudden death. The most
      frequently used drug in the set of patients was amiodarone in monotherapy or in
      combination with other drugs. Sotalol was used for both, its antiarrhythmic
      nature, and for its ability to reduce the defibrillation threshold in patients
      with an implanted automatic implantable cardiovertor-defibrillator (AICD).
      Antiarrhythmic drugs of class I in monotherapy were used in patients with non
      coronary causes of ventricular tachycardia and with normal left ventricular
      function. The authors, on the basis of sudden death of three patients with low
      ejection fraction of the left ventricle which were recorded even despite Holter
      apparatus and electophysiologically confirmed supression of ventricular
      tachycardia, recommend to consider in this group of patients the primary AICD
      implantation. (Tab. 4, Fig. 2, Ref. 13.)

PMID- 9525054
TI  - [Is the response to cardiac pacing controlled by central venous temperature
      physiological?].
AB  - Rate responsive cardiac pacemakers are capable of adapting their pacing rate
      according to metabolic demands in the physical effort and some of the sensors in
      use even according to such physiological stimuli in which the level of metabolism
      remains unchanged. Central blood temperature (CVT) could possibly represent a
      much-needed and searched ideal sensor, which truly reflects physiological
      processes. In order to verify the response of the thermistor sensor under various
      physiological conditions, 10 single-chamber VVIR pacemakers Thermos M 02
      (Biotronik) were implanted since 1993 through 1995. Our group of patients
      consisted of 9 men and 1 women. 8 patients had chronic atrial fibrillation with
      bradycardia and ventricular chronotropic incompetence, 2 patients suffered from
      the 3rd degree atrioventricular block. The mean age at the time of implant was
      62.4 (52-72) years, the mean follow-up period has amounted to 23 (2-32) months.
      The CVT response to physical exercise was proportional and smooth, especially in
      the strenuous physical effort. In contrast to some other sensors, CVT exhibited
      the physiological reaction also in situations in which the metabolic level did
      not change. It displayed a physiological circadian fluctuation of the pacing
      rate. Nevertheless, a markedly prolonged reaction time at the onset of physical
      exercise in the patients who were still "cold" was a shortcoming of this
      principle. The special sensor lead is a must and only the ventricular pacing is
      possible. Isolated CVT is not the ideal sensor but it be combined with fast
      sensors. It will undoubtedly be one of the sensors within the automatic
      multisensor pacemaker in the forseeable future. (Tab. 1, Fig. 1, Ref. 15.)

PMID- 9525055
TI  - [Subacute morphologic changes in the heart after radiofrequency ablation in the
      area of the atrioventricular junction].
AB  - Catheter ablation of the atrioventricular (AV) junction for due to refractory
      supraventricular tachycardias by means of the radiofrequency (RF) current is at
      present an accepted and widespread mode of therapy. Although pathomorphological
      findings of the early postablative period are well documented in animals, only
      few data are available on pathological postablative changes in humans. In this
      paper we present the necropsy findings in a woman who suddenly died 25 days after
      RF ablation of AV junction. In this case the ablative procedure has caused
      subendocardial necrosis revealing signs of advanced organisation with deposits of
      lipofuscin and haemosiderin. We have also found the necrosis of fat tissue in the
      vicinity of the tricuspid anulus in the stage of advanced resorption. The recent
      complication was the thrombotic occlusion of a small branch of coronary artery in
      the right atrial posterior wall causing a nonextensive acute infarction. We
      conclude that our findings are in agreement with the literature data on
      morphologic similarity of ablative lesions and reparative processes in
      experimental models and clinical practice. (Fig. 4, Ref. 8.)

PMID- 9525056
TI  - [Removal of the intravenous pacing system using the inflow occlusion technique].
AB  - Infection of the stimulative system with a septic state or endocarditis is the
      ultimate requirement for the extraction of intravenous parts of the implanted
      stimulative system. The extraction performed by the classical method or by means
      of catheter does not have to be necessarily successful. The use of extracorporeal
      circulation is optimal for the surgeon, however, it is expensive and not
      indifferent for the patient. The inflow occlusion technique under our conditions
      has shown to be fast, safe and an advantageous alternative. We have used it in 11
      patients out of 14. All cases involved an extraction of a foreign body. 78.5% of
      extractions were performed due to infected stimulative system. 2 patients were
      subdued to a simultaneous implantation of DDD, others have had VVI system
      implanted by epimyocardial or transvenous way. We have not been encountered with
      any serious complications. (Tab. 1, Fig. 3, Ref. 7.)

PMID- 9525057
TI  - [Comparison of electrical and radiofrequency ablation of the AV junction in
      patients with refractory supraventricular tachycardia].
AB  - The radiofrequency ablation (RFA) is advantageous due to gradual destruction of
      tissue which enables not only an interruption of conduction, but also its
      modification-retardation of conduction. This state is in most cases sufficient
      for the control of tachycardia. It is necessary to be aware that radiofrequency
      ablation does not coincide with barrotrauma, uncontrollable increase of
      temperature of electrodes and the requirement of general anaesthesis. This
      technique enables the RF ablation therapy: 1. ectopic atrial tachycardia, 2.
      intraatrial tachycardia, 3. atrial flutter of type Z by ablation of the lower
      posterolateral area. (Tab. 1, Fig. 5, Ref. 9.)

PMID- 9525058
TI  - [The head-up tilt test with nitroglycerin provocation in the diagnosis of
      vasovagal syncope].
AB  - The study compares the diagnostical values of "head-up tilt" tests both with or
      without nitroglycerin the provocation. On the basis of the comparison of a group
      of 60 patients and 20 healthy people we can state that the "head-up tilt" test
      with the provocation by nitroglycerin is appropriate for the statement of
      diagnosis of the cardioinhibitory type of vasovagal syncopes. (Tab. 4, Ref. 14.)

PMID- 9525059
TI  - [Pharmacologic and non-pharmacologic therapy of ventricular tachyarrhythmias].
AB  - One of the main causes of cardiovascular death is the sudden death which is most
      frequently caused by malign arrhythmias: ventricular tachycardia (VT) and
      ventricular fibrillation (VF). These fatal disorders of rhythm are not manageable
      effectively by surgery, catheter ablation and pharmacology which cannot be thus
      widely used. Automatic implantable cardiovertors-defibrillators (AICD) have been
      used since 1980 in the therapy of malign ventricular disorders of rhythm. Modern
      AICD in more severe ventricular arrhyhmias have reduced the frequency of sudden
      death from 10-30% yearly to 1%. Our objective was to use preferentially the best
      therapy possible with the least demanding output and the smallest postoperative
      risk, i.e. therapy with transvenous AICD. This was enabled by new apparatuses
      Phylax 03 and Phylac 06 which are able to give the defibrillation shock by
      iridium covered electrodes also without subcutaneous so called "patch"
      electrodes. These circumstances result in a suitable defibrillation threshold.
      (Fig. 2, Ref. 14.)

PMID- 9525060
TI  - [Medical information on Internet sites].

PMID- 9525061
TI  - [How does one become cited?].

PMID- 9525062
TI  - [40 years' of scientific research--an important anniversary of the Parasitology
      Institute of the Comenius University Medical School in Bratislava].

PMID- 9525063
TI  - Prostate-specific antigen and history of its discovery.
AB  - In contradistinction to prostatic acid phosphatase (PAcP), prostate-specific
      antigen (PSA) is currently the most reliable and most frequently used marker for
      identification of normal and pathologically altered prostatic tissues both in the
      male and female. In clinical practice, it has become an appreciated serum marker
      in the assessment and management of prostate carcinoma in the male, although it
      is far from being a perfect "tumor" marker. Our knowledge on female PSA is
      expected to be broadened by the introduction of novel highly sensitive
      serological methods (IMMULITE--immunochemiluminiscent third-generation PSA assay
      and others), which in some females have already demonstrated surprisingly high
      values. Biochemically, PSA in seminal fluid in its free form has a molecular
      weight of about 30,000 daltons, while in serum, where it occurs in the complex
      form with alpha1-chymotrypsin, its molecular weight is approximately 100,000
      daltons being comparable to that of PAcP. On immunohistochemical examination, PSA
      is expressed in the highly specialized apically-superficial layer of male and
      female secretory (luminal) cells of the prostatic glands, as well as at other
      sites of the urogenital tract, frequently coinciding with glucosamine glucans,
      glycoproteins and numerous enzyme proteins. With regard to the increasing
      interest in PSA evidenced in urology, gynecological urology, in the orthology and
      pathology of male and female prostates, the interest in the history of discovery
      of this exceptional prostatic marker appears to be justified. PSA was discovered
      by Richard Ablin and co-workers in the USA, who published their pioneer work in
      the Journal of Reproduction and Fertility and in the Journal of Immunology as
      early as in 1970. Thus their results had been available nine years before the
      publication of Wang et al. appeared in Investigative Urology (1979), on the basis
      of which the latter are frequently incorrectly considered and cited as the
      authors of PSA discovery. (Ref. 46.)

PMID- 9525064
TI  - Modulators and mediators of kidney disease progression: new targets of prevention
      and treatment.
AB  - BACKGROUND: Hemodynamic (i.e. hyperfiltration) and metabolic (i.e. insulin
      resistance) changes are the targets of the present preventive measures of kidney
      disease progression. New horizons of molecular nephrology have extended the
      possibilities in the proliferation research. OBJECTIVES: To review evidence on
      the significance of proliferative processes and the possibilities of interfering
      with proliferation. METHODS: A review of experimental and clinical studies
      elucidating the significance of thromboxane, platelet derived growth factor
      (PDGF) and transforming growth factor-beta (TGF-beta) for the proliferation and
      kidney disease progression. RESULTS: Proliferation participates in the
      development and progression of glomerulosclerosis and interstitial fibrosis. A
      number of growth factors and cytokines trigger and accelerate the progression of
      kidney diseases. A number of PDGF antagonists (i.e. simvastatin, heparin,
      trapidil, tertatol and low protein diet) attenuate the kidney disease
      progression. CONCLUSIONS: Even the present knowledge enables to improve further
      the kidney disease treatment schedules. (Tab. 3, Ref. 22.)

PMID- 9525065
TI  - [Theoretical and clinical significance of neuroplasticity].
AB  - Plasticity is a specific feature of the nervous system, characterized by two
      basic phenomena: The first type of "functional plasticity" develops comparatively
      quickly, brings about mainly functional changes and is usually reversible. The
      second type has the features of an adaptation and affects the expression of
      genotype into phenotype. Neuroplastic mechanisms are triggered by various natural
      or artificial stimuli which may differ quantitatively (they arise in the internal
      or external environment) or qualitatively. Neuroplastic mechanisms are based on
      modulation of the signal transmission over synapses (e.g., the transmitter
      release, activity of postsynaptic receptors, efficiency changes in the
      transmission in the postsynaptic segment). They can be related to the
      interneuronal relations changes (e.g., number of certain types of synapses,
      significance of the wiring of different elements of the neuronal circuits).
      Resulting changes may occur in the communication between neurons (synaptic
      level), in the activity of the local neuronal circuits (level of local circuits)
      or in the relations between individual functional brain systems (multimodular
      level). Neuroplasticity might be based on structural changes which can be
      revealed by morphological methods. Such forms of plasticity are more frequent
      during the development, or as a reaction to injury (proliferation and decease of
      neurons, formation of their processes and spines, remodelling, or formation of
      synapses). More specific methods have determined that these changes are located
      on the molecular level (enzyme activity, production and release of transmitters
      or modulators, receptor activation, modulation of ion channels). Both levels of
      neuroplastic mechanisms bring about changes of functional parameters of the
      synaptic transmission (changes in the duration or amplitude of the membrane
      potentials and resulting facilitation, posttetanic potentiation or changes of
      opposite character). Effects of plasticity can reside either in positive or
      negative changes during the development (evolutional plasticity), after a short
      term exposition (reactive plasticity), after long-term or permanent stimuli
      (adaptational plasticity), and during functional or structural recovery of the
      damaged neuronal circuits (reparation plasticity). Manifestations of plasticity
      have probably the same basis, irrespectively of the cause which has triggered
      them, or the brain region where they have been accomplished. (Tab. 7, Ref. 45.)

PMID- 9525067
TI  - [Single-photon emission-computed tomography in the diagnosis of cerebrovascular
      diseases].
AB  - BACKGROUND: SPECT-HM-PAO allows to detect the regional cerebral blood flow and
      total diminution of the brain perfusion still before morphological substrate
      evolution in CT scan, without invasive technologies. SEARCH GOAL: The authors
      have analyzed data obtained by SPECT-99mTc HM-PAO in the group of 46 patients
      suffering from cerebrovascular disorders and they have compared them with results
      aimed by CT scans. Both, the SPECT-99mTc HM-PAO and CT scan were performed within
      48 hours or later after the onset of the stroke; some of CT scans were repeatedly
      performed. RESULTS: They discovered 40 positive and 6 negative SPECT-HM-PAO
      findings, 26 positive and 20 negative CT scans. SPECT investigation more
      frequently discovers circulatory failures in the clinically altered hemisphere
      than the CT scan does in a substrate; SPECT discloses hypoperfusion of the
      clinically unaltered hemisphere if silent hypoperfusion is present. The
      ipsilateral foci of CT substrates were significantly less frequently observed (p
      < 0.001) than some ipsilateral regional hypoperfusions. Not only the number, but
      also size and extent of hypoperfusional foci searched by SPECT are significantly
      higher and wider than the numbers and dimensions of substrates observed by CT (p
      < 0.001). CONCLUSION: CT scan diagnostic possibilities are restricted by the time
      factor (CT examinations performed within 48 hours since the onset of the stroke
      are significantly less frequently positive than those performed later-p < 0.001).
      SPECT examination has not such a limiting time factor (p > 0.05). MEANING: Hence
      SPECT-HM-PAO renders early, long lasting and wide information on the restriction
      of the overall and regional perfusion, independently of the fact as to whether
      the reduction of cerebral perfusion is, or is not going to result in ischemic
      necrosis and/or ischemic sclerosis. SPECT renders correlation of the perfusion
      disorder earlier, wider in space, and more frequently than the CT scan, and
      therefore it is a prerequisite to the disclosure of the mentioned silent focal
      blood flow reductions. (Graph 12, Fig. 3, Ref. 4.)

PMID- 9525066
TI  - [Precancerous conditions and carcinomas of the stomach and colorectum--blood
      levels of selected micronutrients].
AB  - BACKGROUND: Optimal saturation of organism by micronutrients--vitamins and trace
      elements--has a significant inhibitory effect on the origin and development of
      malign diseases. OBJECTIVES: The aim of the study was to investigate the blood
      levels of A, C and E vitamins, Beta-carotene, zinc, and selenium in 249 patients
      with precanceroses (atrophic gastritis, hyperplastic polyp of the stomach,
      adenomas of the stomach and colorectum, ulcerative colitis), 96 patients with
      carcinoma of the stomach or colorectum, and to compare them with a control group
      of 130 people. RESULTS: We have discovered the frequency of decreased average
      levels of micronutrients in patients with precanceroses as follows: vitamin C >
      vitamins E and A > selenium > beta carotene. In all groups of patients with
      carcinoma the average levels of vitamins and Beta-carotene were significantly
      decreased, the level of selenium has decreased only in the group of gastric
      carcinoma. The copper level was increased in the group of ulcerative colitis and
      in all groups with carcinoma. CONCLUSION: The results indicate that in the
      primary prevention of these malign diseases it is necessary to improve the levels
      of the presented micronutrients in the population of the Slovak Republic by
      increasing the intake of fruit, vegetables and other sources of nutrition, the
      secondary prevention in persons with precanceroses requires an appropriate
      intermittent supplementation of micronutrients (chemoprevention). (Tab. 3, Ref.
      24.)

PMID- 9525069
TI  - [Relation between levels of essential fatty acids in maternal milk, in maternal
      blood and in the blood of neonates 1 and 5 days after birth].
AB  - BACKGROUND: Linolenic, linoleic, and arachidonic acids as well as other
      polyunsaturated fatty acids are necessary for health as the precursors of
      eicosanoids and for the structure of developing membranes. OBJECTIVES: The aim of
      the present study was the determination of the level of 11 individual free fatty
      acids (FFA) in the milk and in the blood of mothers and newborns during the
      perinatal period. METHODS: In 21 women the FFA was determined in their colostrum
      as well as in the venous blood at the delivery in the hospital, and then again 5
      days later at leaving the hospital. Simultaneously, the blood of newborns was
      collected as umbilical samples at birth and as venous blood on the 5th day. The
      study was performed on health term infants and mothers with normal gestational
      age. RESULTS: The results show a marked increase in total milk FFA as well as in
      most, but not all, individual FFAs during the followed period of the first 5
      days. The values in the milk were always remarkably higher (the increase more
      than 2 orders) than in the blood. We have found no significant statistical
      correlation between values in the blood and those in the milk. The concentrations
      of all very important omega-3 FFAs (which are present in fish oil and in foods of
      marine fish origin) were always lower in all blood and milk samples in comparison
      with the levels of omega-6 FFAs (which are prevailing in lipids of our usual
      nutrition as are margarines and most of commercial oils). CONCLUSIONS: Our
      findings seem to be very important for preventive medicine and need to study
      further the relationship of low intake of O3FA to increased incidence of various
      allergies and other pathological syndromes in children. The very large range of a
      variance in the values of FFAs in the milk suggests the need of more profound
      study of the role of the food composition probably during the whole period of
      pregnancy, mainly as to the type of lipid composition. (Tab. 1, Fig. 6, Ref. 24.)

PMID- 9525068
TI  - [Bioenergetics of liver mitochondria after administration of ramipril in
      experimental diabetes mellitus].
AB  - BACKGROUND: Diabetes mellitus represents an intense metabolic strain for the
      liver. Inhibitors of angiotensin-converting enzymes (ACEI) are drugs of choice in
      the therapy of hypertension in coincidence with diabetes mellitus. The effect of
      ACEI is complex. The attention is drawn to the study of metabolic effects of
      ACEI. OBJECTIVES: The aim of the study was to investigate whether the
      administration of ramipril affects the levels of glycated hemoglobin and
      fructoseamine in the blood of rats with insulin-dependent diabetes mellitus
      (IDDM), and whether bioenergetics of mitochondria in the liver undergo changes.
      METHODS: In our experiments, we used rats of the Wistar strain. The control group
      was composed of healthy animals. The experimental groups were formed by rats with
      IDDM evoked by streptozotocine (45 mg/kg) and rats with IDDM + ramipril (10
      mg/KG). Both, insulin MONO-ID in the doses of 6 U/kg administered subcutaneously,
      and water solution of ramipril administered by gastric probe were applied for the
      period of 8 weeks. We have assessed blood levels of glucose, glycated hemoglobin,
      fructoseamine and the concentration of cholesterol and triacylglycerols have been
      assessed also in the liver. Oxidative phosphorylation in mitochondria of the
      liver were measured polarographically. RESULTS: In the group with IDDM +
      ramipril, the glycated haemoglobin (M 6.85 CI 5.7-7.0%) and fructoseamine (M 1.45
      CI 1.2-1.6 mmol/l) have significantly dropped in comparison with the group with
      IDDM glycated haemoglobin (M 8.8 7.7-10.7%) and fructoseamine (M 2.04 CI 1.69-2.4
      mmol/l). Ramipril did not affect the concentration of cholesterol and
      triacylglycerols in the blood and liver in rats with IDDM. Ramipril has
      positively affected oxidative phosphorylation in mitochondria of the liver in
      coincidence with IDDM. The group with IDDM + ramipril has yielded an increase in
      the velocity of oxygen consumption in coincidence with stimulated breathing with
      ADP, the state 3 (M 107.97 CI 96.78-134.51 n AtO/mg of proteins/min.) and
      phosphorylation velocity (M 232.67 CI 209.38-284.97 nmolATP/protein/min) in
      contrast to the group with IDDM: the state 3 (M 76.71 CI 66.81-85.99 nAtO/mg of
      proteins/min and the velocity of phosphorylation (M 161.84 CI 143.55-189.99 nmol
      ATP/mg of proteins/min) in coincidence with substrate glutamate. A similar trend
      is present also in coincidence with FAD succinate substrate. CONCLUSIONS: After
      the administration of ramipril to rats with IDDM, the indicators have improved,
      and they express the rate of compensation of diabetes mellitus. An increased
      capacity of the respiratory chain and an increased origin of energy in
      mitochondria in the livers of rats with IDDM after administration of ramipril
      indicates an improvement in the metabolic capacity of the liver. (Tab. 4. Ref.
      47.)

PMID- 9525070
TI  - [Molecular genetics of sodium channel myopathies].
AB  - The common molecular basis of hyperkalemic periodic paralysis, of paramyotonia
      congenita and that of myotonia fluctuans are the mutations of sodium channel
      SCN4A gene. The mutations result in an increased probability of channel openings
      at rest, or slightly decreased membrane potentials, and in delayed channel
      inactivation, both contributing either to myotonia or paralysis. Because of the
      lack of a sufficient amount of molecular genetic analyses of the above mentioned
      diseases, the precise clinical condition cannot be predicted according to the
      mutation position in the channel polypeptide as the same condition can be caused
      by mutations in different positions and, vice versa, mutations in the same
      position result in different clinical conditions. Causal therapy of these
      conditions is not known yet. (Fig. 1, Tab. 1, Ref. 47.)

PMID- 9525071
TI  - [Present views on indications and techniques in kidney biopsy].
AB  - In the current situation there are available many data on renal biopsies.
      Nevertheless a lot of questions remain unanswered the effectivity and safety of
      the technique of renal biopsy. We demonstrate the current insight on indications,
      contraindications and the technique of renal biopsy. A number of studies in
      recent years have found the biopsy to be of major value in patients with high
      levels of proteinuria, those with signs of systemic disease, and certain patients
      with acute renal failure. We demonstrate our technique of localization of the
      kidney, with marking of location and depth. Continuous ultrasonic guidance is
      used as the needle is inserted into the kidney. Biopsy of kidney is performed by
      an automated technique with Biopty instrument for its safety and better
      effectivity. (Tab. 1, Fig. 6, Ref. 13.)

PMID- 9525072
TI  - [Correlation between biochemical indicators of physical fitness and age].
AB  - 16 men in the average age of 23.7 years and 24 juniors in the average of 17
      years, ice-hockey players, were investigated. A significant negative correlation
      between the physical fitness and indicators of lipoprotein metabolism were found.
      This correlation proved the significance of the intensity of physical activity as
      a factor decreasing the risk factors of atherosclerosis. Significantly higher
      levels of triacylglycerols and significantly lower HDL-cholesterol were found in
      men when compared with the juniors. The comparison of two age categories which
      were subjected to regular long-term physical activity of high intensity, proved
      the influence of the age of ice-hockey players who had been trained under the
      same conditions. Both quantitative and qualitative changes in lipoprotein
      metabolism proved the increase in atherogeneous risks with the increasing age.
      (Tab. 7, Ref. 14.)

PMID- 9525073
TI  - 38th Annual conference of the Indian Society of Gastroenterology, Hyderabad,
      November 6-9, 1997. Abstracts.

PMID- 9525074
TI  - American Federation for Medical Research regional meeting and the annual meeting
      of the Eastern Society for Pediatric Research. February 1998.

PMID- 9525075
TI  - [Intestinal parasitic infections in Serbia].
AB  - To determine the public health significance of intestinal parasitism in Serbia
      today, systematic parasitologic examination of 16 regions (Kragujevac, Luchani,
      Zhagubica, Bor, Sjenica, Novi Pazar, Valjevo, Aleksandrovac, Pirot, Bosilegrad,
      Ivanjica, Golubac, Uzhice, Kladovo, Negotin, Beograd) in central Serbia were
      carried out over the period 1984-1993. The study involved a total of 5981
      schoolchildren (2887 F, 3094 M), 7-11 years old representing 10% of the total age
      matched population (N = 58,228) of the examined regions, residing in 91
      settlements. Field parasitological examinations included the examination of
      perianal swabs for E. vermicularis and Taenia sp., and examination of a single
      feces sample by direct saline smear and Lugol stained smear for intestinal
      protozoa, and the Kato and Lorincz methods for intestinal helminths. Nine species
      of intestinal parasites were detected, of which five protozoan: Entamoeba
      histolytica (0.02%), Entamoeba hartmanni (0.02%), Entamoeba coli (1.3%),
      Iodamoeba butschlii (0.02%), Giardia lamblia (6.8%), and four helminthic:
      Hymenolepis nana (0.06%), Enterobius vermicularis (14.7%), Ascaris lumbricoides
      (3.3%), Trichuris trichiura (1.8%). The overall prevalence of intestinal parasite
      infections amounted to 24.6% (1207/4913), with a highly significant difference (p
      < 0.001) between particular sites (range 14.4%-43.8%) (Figure 1). Helminthic
      infections (810) were significantly more frequent (p < 0.001) as compared to both
      protozoan (296) and combined helminthic-protozoan infections (101). Of these, two
      species (G. lamblia, E. vermicularis) were found in all examined regions, three
      (E. coli, A. lumbricoides, T. trichiura) were detected in two or more, while four
      species (E. histolytica, E. hartmanni, I. butschlii, H. nana) were each found in
      a single region (Figure 2). The predominant species (E. coli, G. lamblia, E.
      vermicularis, A. lumbricoides, T. trichiura) were distributed at considerably
      different prevalence rates, with a significant difference between the minimal and
      maximal values (p < 0.01). Of 91 settlements examined, intestinal parasites were
      found in all but one. However, the prevalence rates in 90 settlements varied
      significantly (p = 0.0004), from a low of 5.9% to a high of 66.7%. Thus,
      according to the World Health Organization criteria [19], infections with the
      four clinically relevant species (G. lamblia, E. vermicularis, A. lumbricoides,
      T. trichiura) ranged from sporadic to endemic and hyperendemic (Figure 3). The
      results obtained provide the basic epidemiological data about intestinal parasite
      infections in Serbia, and indicate their significance in terms of both the number
      of species and their respective prevalence rates. Given the significant
      differences obtained in the frequency and distribution of particular parasite
      infections in different regions, a programme for the control of these infections
      in Serbia should obviously include a wide variety of measures.

PMID- 9525076
TI  - [Sodium balance in premature infants].
AB  - INTRODUCTION: The understanding of water and electrolytes metabolism is essential
      in providing an adequate therapy in the treatment of low birth weight infants. In
      the first days of life sodium balance is negative [10, 11], since sodium renal
      loss is rather big and sodium peroral intake is inadequate [12]. It is not
      recommended to add sodium in the first 24-48 hours of life to extremely immature
      babies (Usher) [13]. The daily requirements of sodium in preterm infants range
      from 2 to 3 mmol/kg. Sodium intake should be adjusted to each patient,
      considering the gestational age, the severity of illness, plasma sodium
      concentration, sodium excretion by urine, which depends on morphological maturity
      and reabsorbitional capacity of the proximal tubule. AIM OF THE STUDY: Aim of the
      study was to investigate the relation between sodium balance and body weight gain
      in the first 10 days of life in preterm infants on different feeding regimens.
      METHODS: Twenty-one preterm infants, gestational age from 28 to 36 weeks,
      eutrophic, postnatal age from 1 to 10 days, treated at the Institute for Preterm
      Infants in Belgrade, were included in the study. All infants were divided into
      three groups: the first group, eight babies, fed by mothers' milk, were
      additionally given 10% glucose with physiological solution of sodium chloride;
      the second group, six infants, also fed by mothers' milk, were additionally fed
      by amino acids, and 10% glucose solution and physiological sodium chloride
      solution; the third group, seven infants, were on total parenteral nutrition (10%
      glucose solution, 0.9% sodium chloride solution, amino acis and fatty emulsions).
      We organised a prospective balance study over the period from 20.01, to
      01.11.1986 during which we calculated sodium retention by measuring sodium intake
      and urine sodium excretion. All infants had the same fluid intake from 70 to 150
      ml/kg/day, both enteral and parenteral. Sodium intake varied from 1 to 3
      mmol/kg/day. Sodium excretion was measured on the fifth and tenth day of life in
      a 24-hour-urine collection and was calculated by the following formulas: Osmolal
      index was calculated as urine osmolality-serum osmolality ratio. Osmolal
      clearance was calculated: Water balance was calculated on the basis of total
      fluid intake in ml/kg/day and diuresis in ml/kg/day. RESULTS: The initial body
      weight loss was within physiological limits, 7-8% of the birth weight. In the
      study period none of the infants achieved his/her birth weight. In the third
      group the weight gain was 3% comparing to the birth weight, which was
      statistically significant (p < 0.05) (Table 2). The sodium intake was within
      expected levels-from 1.32 to 2.03 mmol/kg/day. Sodium intake was statistically
      higher in the third group (2.03 mmol/kg/day) than in the first and second groups
      (p < 0.05). We found negative sodium balance in three infants in the first group
      and two in the second group, and in all infants of the third group sodium balance
      was positive on the fifth day of life. We found no statistically significant
      differences among the groups when testing their sodium balances by hi-square test
      (Graph 2). When studying serum and urine osmolality and calculating osmolality
      index and osmolar clearance, we found that these levels were between normal
      values, without statistically significant differences among the groups (Graph 3).
      Sodium, protein, urea and creatinine levels were also normal, without
      statistically significant differences among the groups (Table 3). DISCUSSION: On
      the basis of our study we can emphasize the following findings regarding the
      relation between weight gain and sodium balance. In the first group three babies
      started with weight gain from 6th to 10th day of life. In the second group six
      babies started with weight gain in the same period-from 6th to 10th day. Gain
      weight of babies in the third group was by 3% greater in the same period compared
      to the birth weight, what makes a significant difference (p < 0. (ABSTRACT
      TRUNCAT

PMID- 9525077
TI  - [Neuroendocrine response in patients with uveitis].
AB  - Uveitis is a group of inflammatory eye diseases whose origin is not yet known. It
      is supposed that they are autoimmune diseases, mediated by T cells, but the
      triggering mechanism is unknown. In the past few years the role of prolactin, as
      an immunomodulator, has been investigated. Its effect on cellular and humoral
      immunity has been brought in evidence by the presence of its receptors on the
      surface of immune cells. It has also been shown, that the presence of PRL is
      necessary for proliferation and maturation of immune cells. On the other hand,
      PRL-like molecule, whose effect is similar to that of pituitary PRL, is secreted
      by human lymphoid tissue as well as by peripheral mononuclear cells. The role of
      glucocorticoids in immunomodulation is based on their effects on immune system by
      inhibition of production of immune cells and their products, cytokines.
      Cytokines, which are produced during the immune reactions mediated by T cells,
      demonstrate their effect in autocrine and paracrine fashion, but when delivered
      in higher concentrations, can be found in blood, when they act at the hypothalamo
      pituitary level. There are three opinions how they act at this level. The aim of
      the study was to investigate the role of prolactin and cortisol in the
      development of endogenous uveitis. The prospective study comprised 42 patients
      suffering from endogenous uveitis. Ten patients were controls. Prolactin
      concentrations were within normals, while cortisol concentrations were
      significantly decreased. We speculated the possible causes of such conditions,
      supposing that the hypothalamo-pituitary-adrenal axis disturbance could be the
      one. In conclusion, we would like to emphasize that in uveitis there is a
      disturbance at neuroendocrine/immune system level, and that uveitis is a systemic
      disease with ocular manifestation.

PMID- 9525078
TI  - [Blood selenium in healthy persons and individuals with malignant diseases].
AB  - INTRODUCTION: Preliminary researches taken part in Yugoslavia showed the risky
      low concentration of selenium in soil, food items and in serum of the examined
      population [10]. This research was carried out to discover the some factors which
      could influence the relationship of serum selenium concentration and the
      appearance of malignant diseases. METHODS: The investigation was carried out in
      two Belgrade communities, one rural (Barajevo), and the other central (Stari
      Grad), in two groups: cancer patients (57 + 17) and healthy controls (41 + 13).
      These groups were similar in median age and gender. Samples of human serum were
      obtained by venepunction, and after wet digestion selenium concentration was
      determined by hydride generated AAS (Perkin-Elmer 5000). Anamnestic data
      concerning family history of malignancy and comorbidity, especially chronic
      noncommunicable diseases, were collected by questionnaire. All the participants
      were asked about their health related habits like: cigarette smoking and alcohol
      consumption. Dietary habits were assessed by food frequency method. Body mass
      index (BMI) was calculated as the parameter of nutritional status. RESULTS: The
      mean serum selenium level in cancer patients and healthy control (Table 1) were
      not significantly different. But, both cancer patients and healthy controls from
      Barajevo have significantly lower values comparing to those living in Stari Grad.
      Table 2 shows the relationship between serum selenium level and various
      environmental factors. The factors identified as the most important are: living
      in community Barajevo, age, history of chronic disease and some dietary factors.
      The univariate analysis (Table 3) revealed that factors like cigarette smoking,
      alcohol consumption, family history of malignancy and comorbid states were not
      important predictive factors for patient malignant disease. The multivariate
      analysis revealed that consumption of sugar, fat and fruit were of the highest
      predictive value in assessing cancer relative risk. DISCUSSION: The results of
      selenium serum level in investigated population are in agreement with those
      published by Maksimovic [10]. They are among the lowest concentrations in Europe,
      especially in participants living in Barajevo. Thought the number of
      investigators found generally lower serum selenium levels in cancer patients, the
      finding is not entirely consistent [14, 15], and so are the results obtained
      here. Consumption frequency calculated for 44 food items which may be most
      important source of dietary selenium intake (like: meat, fish, diary products and
      cereals), didn't show important relationship with serum selenium levels. People
      living in Barajevo consume food grown in their own soils (proofed deficient with
      selenium), and this might the reason for the striking differences in serum
      selenium levels between people living in Barajevo and Stari Grad. CONCLUSION: The
      results obtained in this investigation indicated that serum selenium level is low
      both groups cancer patients and healthy controls too. Food items identified as
      sources of selenium in diet are not connected with this low selenium level.

PMID- 9525079
TI  - [Treatment of the thoracic outlet vascular syndrome].
AB  - INTRODUCTION: The title "Thoracic Outlet Syndrome" (TOS) was introduced by Peet
      in 1956 [1]. In 1958 Charles Rob defined TOS as a "set of symptoms that may exist
      due to compression on the brachial plexus and on subclavian vessels in the region
      of the thoracic outlet" [2]. Compression due to cervical rib was first described
      by Galenus and Veaslius in the 2nd century A.D. The first unsuccessful resection
      of the cervical rib in patients with TOS was performed by Coote in 1861 [4]. In
      1905 Murphy first made a successful resection of the cervical rib in patients
      with TOS and subclavian artery aneurysm [5]. He also removed the normal first rib
      in patients with TOS using the supraclavicular approach for the first time [6].
      In 1920 Law described ligaments and other structures originating in soft tissue
      associated with TOS [8], while Adson and Coffey in 1927 emphasized the role of
      the scalene anticus muscle in TOS [3]. Ochsner, Gage and DeBakey in 1935 named it
      the "scalenus anticus syndrome", and made the first successful resection of the
      anterior scalene muscle [9]. In 1966 David Ross introduced the transaxillary
      resection of the first rib to relieve TOS [11]. The aim of the paper is to
      describe the treatment of patients with vascular TOS. MATERIAL AND METHODS: Over
      a six-year-period (1990-1997) 12 patients with vascular TOS were evaluated at our
      Centre. Seven (58%) were female and 5 (42%) male patients, average age 33.1
      years. Eleven of them had congenital TOS, and one acquired TOS after trauma at
      neck-shoulder region. Seven patients had arterial and 5 venous TOS. Two patients
      with arterial TOS had ischaemia of the upper extremity due to embolism of the
      brachial artery. In one of them axillary artery was completely thrombosed, and in
      the other postenotic dilatation of the subclavian artery was present. The other 5
      patients with arterial TOS demonstrated only hand pain and radial puls during
      hyperabduction of the arm. One of our patients with venous TOS had also symptoms
      and signs of hand oedema during hyperabduction, while four patients had axillary
      subclavian deep venous thrombosis (DVT). All patients underwent CW-Doppler and
      Duplex-ultrasonographic examination. The results were positive in all patients
      with arterial TOS. The angiographic (selective arteriography of the subclavian
      artery) examination showed the same results. Diagnostic procedures were performed
      in normal position of the arm and during hyperabduction. The angiography also
      revealed: one aneurysm of the subclavian artery, one poststenotic dilatation of
      the subclavian artery with brachial artery embolization, and one thrombosed
      axillary artery with brachial artery embolization (Figure 1). In five patients
      the angiogram was normal in normal position of the arm, but showed arterial flow
      obstruction at the thoracic outlet during hyperabduction (Figures 2a and 2b). In
      patients with venous TOS Duplex ultrasonographic examination was performed. The
      cervical rib caused TOS in four of our patients and clavicle fracture calus in
      one case. In 7 patients bone anomalies were not found (Figure 3). The operative
      treatment was carried out in 3 patients with venous and 7 patients with arterial
      TOS. In two patients with DVT of the axillary-subclavian segment, 6 months after
      standard anticoagulant therapy, decompressive procedures were performed (one
      resection of the cervical rib, and one transauxillary resection of the first
      rib). In the case of venous TOS without DVT, a supraclavicular resection of the
      first rib was performed immediately after diagnosis. In 5 patients with arterial
      TOS without morphologic changes on the arterial system, a decompressive procedure
      was done. The following procedures were carried out: one scalenotomy, one
      supraclavicular and three transaxillary resections of the first rib. (ABSTRACT
      TRUNCATED)

PMID- 9525080
TI  - [Results of surgical treatment of retained testes].
AB  - INTRODUCTION: Numerous papers discuss different opinions about determination of
      the best age for initiation of an appropriate medical or surgical therapy
      suggesting in this way modern dilemmas about this congenital malformation. All
      this emphasizes the importance of the problem, classification of professional
      disagreements and initiation of correct management of these malformations in
      order to reduce the consequences to the least possible level. The aim of the
      study was to emphasize the importance of the prompt diagnosis and surgical
      treatment at the best age in order to preserve the testicular function. MATERIAL
      AND METHODS: The study included 84 patients, aged 2-49 years, operated on at the
      Chachak Urological Ward of Surgical Department over the period 1990-1996. RESULTS
      AND DISCUSSION: The majority of the patients were between 6 and 10 years of age
      (3%) (Table 1, 2). Left side retention was predominant (48%), while bilateral
      retention was recorded in 14% of patients. Inguinal retention was the most common
      (76%), testicular ectopia (2%), while there was 7% of patients with testicular
      anorchia. SURGICAL METHOD: Funiculolisis and orchiopexy (Schoemaker's operation).
      Hernioplasty was performed in 38% and semicastration in 7% of patients.

PMID- 9525082
TI  - [Hypersensitivity to mites and house dust].
AB  - The paper deals with the current data on hypersensitivity to house dust
      allergens, particularly to house dust mite allergens. Hypersensitivity to house
      dust mites is more prevalent than hypersensitivity to any other allergen.
      Ecologic factors for mite survival are cited, particularly emphasizing the
      importance of air humidity. Over the last 50 years there have been several
      changes in construction and furnishing of houses in developed countries which
      fostered mite proliferation. Mite allergens are identified and cloned, monoclonal
      antibodies to these allergens are produced. There are methods for estimating mite
      allergen concentration in homes which made possible to investigate the
      relationship between mite allergen exposure and development of bronchial
      hyperreactivity. Various methods for mite allergen avoidance are developed and
      their efficacy is under investigation.

PMID- 9525081
TI  - [Significance of merosin and sarcoglycan in manifestations of certain forms of
      muscular dystrophy].
AB  - The muscular dystrophy is a progressive genetically determined disease of
      skeletal muscles. Thanks to the development of molecular genetics there have been
      identified genes responsible for synthesis of the corresponding proteins of the
      muscular membrane, whose deficiency causes certain types of muscular dystrophy.
      Thus, recently has been reported that deficiency of sarcoglycan (alpha, beta,
      gamma and sigma) is responsible for the appearance of four different types of
      autosomal recessive limb-girdle muscular dystrophies (2D, 2E, 2C, 2F), and that
      the lack of merosin is the cause of serious merosin deficiency, of congenital
      muscular dystrophy. The paper presents the nature, function and importance of the
      main components of sarcolemma, as well as the basic characteristics of muscular
      dystrophies caused by their deficiency. It is important to know the genetic
      product whose deficiency is responsible for certain types of muscular dystrophy
      as only by confirming their deficiency in the biopsy material the precise
      diagnosis can be established even without molecular-genetic analyses. This is of
      great importance for accurate genetic advising.

PMID- 9525083
TI  - [The role of mononuclear phagocytes and dendritic cells in allergic
      inflammation].
AB  - Mononuclear-phagocytic system is a diffuse network of cells which includes
      monoblasts and promonocytes of the bone marrow, blood monocytes, as well as free
      and fixed tissue macrophage cells. In different tissues and organs macrophages
      acquire different morphological and functional properties under the influence of
      the local tissue factors. Interaction of macrophages with other cells and
      molecules is performed via the large number of different receptors resulting in
      activation of the macrophage cell, accompanied by a series of morphological and
      metabolic changes which potentiate all its functions. Activated macrophage cells
      were found in certain diseases. Macrophages and dendritic cells are associated
      with all aspects of immunity. Owing to their capacity to undergo phagocytosis
      they are of the utmost importance for unspecific defense from microorganisms. As
      accessory cells they also participate in cellular and humoral immunity, being at
      the same time effector cells owing to their capacity of antigen presentation.
      Moreover, they also participate in immune response regulation owing to their
      influence on the function of other cells, including mast cells, basophilic
      leukocytes and T lymphocytes, in which they may influence differentiation toward
      Th1 or Th2 and cytokine milieu favorable for allergic reaction. Dendritic cells
      are the most important antigen-presenting cells and thus, they play a major role
      in activation of helper T lymphocytes, and mode of antigen presentation is
      significant for regulation of the nature and intensity of the immune response.
      Pulmonary macrophage cells have been most thoroughly studied, and the observed
      changeability of their functional and morphological characteristics is of the
      utmost importance for studying of the pathogenetic properties and regulation of
      the chronic inflammatory response in bronchial asthma.

PMID- 9525084
TI  - [The role of thrombocytes in allergic inflammation].
AB  - The platelet has traditionally been associated with haemostasis. Participation of
      platelets in defence mechanisms is presentiment by the knowledge that primary
      haemostasis may be phylogenetic vestige retained from the behaviour of primitive
      leukocytes. Platelets have the ability to undergo shape change with pseudopod
      formation, chemotaxis, diapedesis, and phagocytose. Platelets contain a wide
      range highly potent inflammatory factors that are capable of inducing or
      augmenting certain inflammatory responses. Different surface molecules have been
      detected on the plasma membrane, highlight the platelets ability to bind a
      variety of biologic surfaces, including those of other cells, resulting in close
      apposition of platelets and their targets. They can interact with parasites,
      viruses and bacteria. Studies from several groups suggest an important role of
      the platelet in allergic processes. Platelets possess receptor for immunoglobulin
      E. Numerous clinical reports are describing the modification of biologic activity
      of platelets from allergic patients as compared to healthy subjects. The
      incidence of abnormal platelet responsiveness is in higher among patients having
      high serum IgE titres. Platelet depletion decreased the anaphylactic response and
      protects against the lethal consequences of the antigen provocation. Evidence now
      exists in support of primary role of the platelet in the pathogenesis of
      bronchial asthma. Platelets can participate in allergic asthma by acting as
      inflammatory cells, by releasing spasmogens and by interacting with other
      inflammatory cells. Thrombocytopenia and the increased plasma levels of platelet
      derived markers occurred in parallel with bronchoconstriction induced by antigen
      provocation of allergic astmatics. Platelet depletion inhibits the ability of
      antigen to induce late onset airways obstruction and airway hyperresponsiveness.
      Platelet apheresis in human resulted in a positive clinical effect. Platelets
      respond to aspirin or other NSAIDs in acetyl salicylic acid sensitive asthmatics
      and these findings provide further evidence for role of the platelet in this form
      of bronchial asthma.

PMID- 9525085
TI  - [Laparoscopic-assisted vaginal hysterectomy at the Dr. Dragisa Misovic-Dedinje
      Clinical Center].

PMID- 9525087
TI  - Atlas of mortality in Europe. Subnational patterns 1980/1981 and 1990/1991.

PMID- 9525086
TI  - [Medical manuscript of Mihail Plamenac, a priest].
AB  - It is known that collections of popular medical prescriptions and instructions
      appeared in areas without educated physicians, and all previously published
      manuscripts of this kind are inevitably anonymous. The reported manuscript
      comprises 23 pages written in sepia ink, appendixed to a prayer book published in
      1747, containing popular medical instructions and prescriptions collected and
      practiced by orthodox priest Mihailo Plamenac in Montenegro at the turn of the
      18th century. Mihailo Plamenac took an important part in historical events, as
      documented by numerous domestic historical data and several letters discovered in
      The Archives of Vienna. Being the only literate persons at the time, priests were
      both politicians and military officers, but they also offered medical services to
      the population. The manuscript comprises advices for various common emergencies
      (snake bites, urinary retention, contusions, fever, burns, eye injuries, rabies,
      otitis, traumatic wryneck) and diseases(impetigo, scabies, infertility, gastric
      ulcer, low back pain) as well as for certain poorly defined conditions (chest
      pain, abdominal discomfort). Besides medically fully adequate treatment, for
      example, the remedy against scabies containing sulfur, there are numerous
      examples of magic and ritual pagan elements, including famous medieval SATOR
      formula against rabies. Most of the herbs used in prescriptions have been
      identified: fig, dog rose, hyssop, leek, laurel, absinthe, rosemary, mallow,
      cypress, elder, endive, mangel, orache, ivy. The manuscript is the first
      manuscript undoubtedly attributed to a well known historical personality, as
      indicated in the first page of the manuscript: "This is a medical prayer book by
      Mihailo Plamenac, left to him by his ancestors."

PMID- 9525088
TI  - Albumin conjugates of the anticancer drug chlorambucil: synthesis,
      characterization, and in vitro efficacy.
AB  - In our efforts to improve the selectivity and toxicity profile of antitumor
      agents, four maleimide derivatives of chlorambucil (1-4) were bound to thiolated
      human serum albumin which differ in the stability of the chemical link between
      drug and spacer. 1 is an aliphatic maleimide ester derivative of chlorambucil,
      whereas 2-4 are acetaldehyde, acetophenone, and benzaldehyde carboxylic hydrazone
      derivatives. HPLC stability studies at pH 5.0 with the related model compounds 5,
      7, 8, and 9, in which chlorambucil was substituted by 4-phenylbutyric acid,
      demonstrated that the carboxylic hydrazone derivatives have acid-sensitive
      properties; the acid lability of 7 was particular prominent with a half-life of
      only a few hours. The alkylating activity of albumin-bound chlorambucil was
      determined with the aid of 4-(4-nitrobenzyl)-pyridine (NBP), demonstrating that
      on average three equivalents were protein-bound. Evaluation of the cytotoxicity
      of free chlorambucil and the respective albumin conjugates in the MCF7 mamma
      carcinoma and MOLT4 leukemia cell line employing a propidium iodide fluorescence
      assay demonstrated that the conjugate in which chlorambucil was bound to albumin
      through an ester bond was not as active as chlorambucil. In contrast, the
      conjugates in which chlorambucil was bound to albumin through carboxylic
      hydrazone bonds were as or more active than chlorambucil in both cell lines. In
      particular, the conjugate in which chlorambucil was bound to albumin through an
      acetaldehyde carboxylic hydrazone bond exhibited IC50 values which were
      approximately 4-fold (MCF7) to 13-fold (MOLT4) lower than those of chlorambucil.
      Preliminary toxicity studies in mice showed that this conjugate can be
      administered at higher doses in comparison to unbound chlorambucil.

PMID- 9525091
TI  - Anti-inflammatory properties of new adamantane derivatives. Design, synthesis,
      and biological evaluation.
AB  - A series of adamantane-containing molecules consisting of two lipophilic centers
      which are linked by different bridges (oxime esters, oxime ethers, amides, and
      symmetric alcohols), were designed and synthesized as anti-inflammatory agents.
      Their anti-inflammatory activity was evaluated as their ability to inhibit
      phlogistic-induced mouse paw edema. Some of the tested compounds exhibited
      activity comparable to that of diclofenac, others had a weaker activity, while
      some oxime esters proved to enhance the inflammatory response. In all cases,
      activity was dose-dependent. The deacylated compound 10 was found to be the most
      active of the series, inhibiting inflammation due to Baker's yeast, the mechanism
      of which involves mainly the activation of lipoxygenase and/or complement
      systems, a property which is absent from most selective cyclooxygenase only
      inhibiting non-steroidal anti-inflammatory drugs (NSAIDs).

PMID- 9525089
TI  - Research on potentially bioactive aza and thiaza polycyclic compounds containing
      a bridgehead nitrogen atom. Synthesis and antimicrobial activity of some
      pyrrolo[1,2,3-de]-1,4-benzothiazines, Part 2.
AB  - Acid catalyzed cyclization reactions of both 3-alkyl- and 3-aryl-substituted N
      (2,2-dialkoxyethyl)-3,4-dihydro-2H-1,4-benzothiazines (2) lead to 2,3-dihydro
      pyrrolo[1,2,3-de]-1,4-benzothiazines (3). The pyrrolobenzothiazine structure was
      deduced on the basis of 2D 1H NMR-NOESY experiments and fully determined by X-ray
      data. Compounds 3a-c showed poor antibacterial activity. However, the 3-phenyl-N
      (2,2-dimethoxyethyl)-3,4-dihydro-2H-1,4-benzothiazine (2b') showed antifungal
      activity against Aspergillus niger 16-fold greater than miconazole.

PMID- 9525090
TI  - Structure activity relationship of homochiral 7-substituted 1-aminoindans as 5
      HT1A receptor ligands.
AB  - A series of homochiral 7-substituted 1-aminoindans was prepared by means of
      asymmetric reductive amination from racemic 7-substituted 1-indanones via E
      imines and E-imine/enamine mixtures, respectively, and subjected to 5
      hydroxytryptamine (5-HT) receptor subtype binding studies. The ee's of the title
      compounds were determined by HPLC of the corresponding Mosher's amides and range
      from 96 to 99.9%. The absolute configuration was elucidated by means of
      correlation CD spectroscopy. On the basis of the pK1 values obtained from various
      test systems, structure activity relationships have been established with respect
      to the absolute configuration, degree of N-alkylation, and the type of 7
      substituents. The tested 1-aminoindans show the highest affinity to the 5-HT1A
      receptor, with decreasing magnitude for the 5-HT2A, 5-HT1D, and 5-HT2C receptors.
      The highest affinities for the 5-HT1A receptor were observed for the R-(-)-7
      propoxy-1-(di-n-propylamino)indan hydrochloride (R-(-)-30). S,S'-(+)-7
      benzylamido-1-(1-phenylethylamino)indan hydrochloride [S,S'-(+)-19] and R-(-)-7
      methoxy-1-(di-n-propylamino)indan hydrogenembonate (R-(-)-29) with pK1 = 7.07 +/-
      0.19, 6.40 +/- 0.09, and 6.22 +/- 0.10, respectively, in comparison to 8-OH-DPAT
      with pK1 = 8.70 +/- 0.30. Nearly all other compounds showed low affinity at all 5
      HT receptors tested. The three above mentioned ligands were tested on HeLa cells
      (cell line HA6) expressing recombinant human 5-HT1A receptors for their effects
      on forskolin-stimulated cAMP accumulation in intact cells. Both the di-n
      propylamino substituent bearing R-(-)-30 and R-(-)-29 acted as efficacious
      agonists with a pEC50 value of 5.89 +/- 0.20 for R-(-)-30 compared to 5-HT with a
      pEC50 value of 8.06 +/- 0.14, S,S'-(+)-19 with the 1-phenylethylamino substituent
      was devoid of intrinsic activity up to the highest tested concentration (10
      microM).

PMID- 9525092
TI  - New NO-donors with antithrombotic and vasodilating activities, Part 19.
      Pseudonitroles and their dimeric azodioxides.
AB  - Thirteen geminally substituted nitro-nitroso compounds (pseudonitroles) have been
      synthesized, four of them for the first time. In the solid state the
      pseudonitroles are dimerized to azodioxides. This is proved by IR spectroscopy,
      with the dimeric N-O valence vibration being observed between 1293 and 1306 cm-1.
      Only 1,3-diphenyl-2-nitro-2-nitrosopropane is monomeric even when solid. This is
      backed by its blue color and an IR band at 1574 cm-1. When dissolved in
      chloroform these azodioxides dissociate completely to the blue monomers (lambda
      max approximately 650 nm). Eight pseudonitroles inhibited the aggregation of
      blood platelets half-maximally at concentrations below 10 microM (Born test,
      collagen). When administered orally to rats (60 mg/kg) the thrombus formation in
      mesenteric arterioles and venules was inhibited up to 25 percent (k; 1-nitro-1
      nitrosocyclohexane). When kept in aqueous media at 37 degrees C nitric oxide and
      its reduced from, i.e. nitrosohydrogen, are released. This suggests that the
      above biological effects arise from an NO dependent mechanism. The lack of
      influence on the blood pressure of spontaneously hypertensive rats, however,
      strongly suggests that an enzyme supported rather than a thermal formation of NO
      occurs in vivo.

PMID- 9525093
TI  - Audience perceptions of politicians' self-presentational behaviors concerning
      their own abilities.
AB  - Effects of self-presentational behaviors of 2 German politicians during an
      election campaign were analyzed. Six scenes from interviews with the politicians
      were presented to 43 German students, who qualitatively evaluated the
      politicians' performances. The participants did not perceive behaviors such as
      interrupting journalists, brushing off criticism, reacting with countercriticism,
      and attacking the opponent personally as indicators of strength but interpreted
      them as signs of aggression and arrogance. On the other hand, the participants
      associated calm reactions to criticism, focused attacks on the opponent, and
      explanations of opinions and plans with self-assurance and competence. Although
      the participants evaluated overt positive self-description negatively, they
      evaluated indirect self-enhancement positively. The participants' party
      affiliations were largely unrelated to their evaluations.

PMID- 9525094
TI  - AIDS knowledge and attitudes of health-care workers in Mexico.
AB  - AIDS threatens to spread rapidly in Mexico. In the present study, results of a
      survey of 204 Mexican employees in hospitals and doctors' offices indicated that
      those health-care workers were largely knowledgeable about the illness. A
      majority were willing to provide AIDS care, although they feared contagion.
      Multiple regression analyses indicated that (a) attitudes toward high-risk groups
      (intravenous drug users and homosexuals) and (b) fear of contagion were both
      related to intentions to provide care to AIDS patients.

PMID- 9525095
TI  - Psychometric properties of the social-conflict scales for Chinese adolescents.
AB  - Despite the gradual increase of research on social conflicts, psychometric
      characteristics of social-conflict scales have not been extensively examined,
      especially in the adolescent population. In this study, the internal consistency,
      test-retest reliability, and criterion-related validity of 2 established social
      conflict scales were examined in a sample of 581 Chinese adolescents. There were
      high internal consistencies and test-retest reliabilities for both the Family
      Conflict Scale and the Friend Conflict Scale. The scales were significantly
      related to appraisals of the quality of social relations, psychological distress,
      and trait anxiety.

PMID- 9525096
TI  - Assessments of trust in intimate relationships and the self-perception process.
AB  - Assessments of trust in intimate relationships are often based on perceptions of
      a partner's behaviors; however, people's own actions, increased self-awareness,
      and individual differences (e.g., exchange or communal orientation) may also
      affect their trust in their partners. Communally or exchange-oriented members of
      heterosexual dating couples, students in a U.S. university, displayed either
      trusting or irrelevant behaviors under conditions of increased self-awareness.
      They then completed measures of interpersonal trust. The participants' trusting
      behaviors significantly determined their level of trust; heightened self
      awareness and a communal orientation further enhanced the participants' trust in
      their partners.

PMID- 9525097
TI  - A longitudinal study of the relationship between attributional style, life
      events, and depression in Japanese undergraduates.
AB  - A longitudinal design was used to investigate the relationship between
      attributional style, life events, and depression in Japanese undergraduates. The
      1st hypothesis tested was that among those experiencing negative events, the
      students with a depressogenic attributional style would be more depressed than
      those with a nondepressogenic attributional style. The 2nd hypothesis tested was
      that among those experiencing positive events, the students with an enhancing
      attributional style would be less depressed than those with a nonenhancing
      attributional style. A total of 143 undergraduates responded to a depression
      scale, a life event questionnaire, and an attributional style questionnaire. The
      results, which generally supported the hypotheses, may reflect cultural
      differences between Japan and the United States.

PMID- 9525098
TI  - Affiliation, gender, and parental status among homeless persons.
AB  - Affiliation, loss of affiliation, and the associated effects on homeless
      individuals were assessed via a survey of 230 homeless adults in Florida. Women
      accompanied by dependent children, unaccompanied women, and unaccompanied men
      were compared regarding levels of affiliation and associations among affiliation,
      self-esteem, and locus of control. The women accompanied by children maintained
      more family contacts and had higher levels of self-esteem; for the group, locus
      of control was more external than for either the unaccompanied women or the
      unaccompanied men. Women with children also had the lowest median number of days
      homeless and the highest average monthly incomes.

PMID- 9525099
TI  - Attributions for youth crime among British and Nigerian primary school children.

PMID- 9525100
TI  - Plant-derived leading compounds for chemotherapy of human immunodeficiency virus
      (HIV) infection.
AB  - Many compounds of plant origin have been identified that inhibit different stages
      in the replication cycle of human immunodeficiency virus (HIV): 1) virus
      adsorption: chromone alkaloids (schumannificine), isoquinoline alkaloids
      (michellamines), sulphated polysaccharides and polyphenolics, flavonoids,
      coumarins (glycocoumarin, licopyranocoumarin) phenolics (caffeic acid
      derivatives, galloyl acid derivatives, catechinic acid derivatives), tannins and
      triterpenes (glycyrrhizin and analogues, soyasaponin and analogues); 2) virus
      cell fusion: lectins (mannose- and N-acetylglucosamine-specific) and triterpenes
      (betulinic acid and analogues); 3) reverse transcription; alkaloids
      (benzophenanthridines, protoberberines, isoquinolines, quinolines), coumarins
      (calanolides and analogues), flavonoids, phloroglucinols, lactones
      (protolichesterinic acid), tannins, iridoids (fulvoplumierin) and triterpenes; 4)
      integration: coumarins (3-substituted-4-hydroxycoumarins), depsidones, O-caffeoyl
      derivatives, lignans (arctigenin and analogues) and phenolics (curcumin); 5)
      translation: single chain ribosome inactivating proteins (SCRIP's); 6)
      proteolytic cleavage (protease inhibition): saponins (ursolic and maslinic
      acids), xanthones (mangostin and analogues) and coumarins; 7) glycosylation:
      alkaloids including indolizidines (castanospermine and analogues), piperidines (1
      deoxynojirimicin and analogues) and pyrrolizidines (australine and analogues); 8)
      assembly/release: naphthodianthrones (hypericin and pseudohypericin),
      photosensitisers (terthiophenes and furoisocoumarins) and phospholipids. The
      target of action of several anti-HIV substances including alkaloids (O-demethyl
      buchenavianine, papaverine), polysaccharides (acemannan), lignans
      (intheriotherins, schisantherin), phenolics (gossypol, lignins, catechol dimers
      such as peltatols, naphthoquinones such as conocurvone) and saponins (celasdin B,
      Gleditsia and Gymnocladus saponins), has not been elucidated or does not fit in
      the proposed scheme. Only a very few of these plant-derived anti-HIV products
      have been used in a limited number of patients suffering from AIDS viz.
      glycyrrhizin, papaverine, trichosanthin, castanospermine, N-butyl-1
      deoxynojirimicin and acemannan.

PMID- 9525101
TI  - Acidic polysaccharide from Panax ginseng, ginsan, induces Th1 cell and macrophage
      cytokines and generates LAK cells in synergy with rIL-2.
AB  - We previously reported that an acidic polysaccharide from Panax ginseng named
      ginsan inhibits the incidence of benzo[a]pyrene-induced autochthonous lung tumors
      in mice. To elucidate the mechanism of antineoplastic activity, ginsan was tested
      for its ability to generate LAK cells and to produce cytokines. Spleen cells
      became cytotoxic to a wide range of tumor cells after 5 days of culture with
      ginsan in a non-major histocompatibility restricted manner and the activity of
      ginsan was 12 times higher than that of lentinan. The generation of killer cells
      by rIL-2 was neutralized only in the presence of anti-IL-2, whereas by ginsan it
      was neutralized in the presence of anti-IL-2 as well as anti-IFN gamma, or anti
      IL-1 alpha. It was confirmed that ginsan induces the expression of mRNA for IL-2,
      IFN gamma, IL-1 alpha, and GM-CSF. Depletion of AsGM1+ cells from spleen cells
      reduced the generation of LAK by rIL-2. In contrast, depletion of AsGM1+ as well
      as Thy1+ cells, CD4+ cells, or DC8+ cells reduced the generation of LAK cells by
      ginsan. The serologic phenotype of rIL-2 induced LAK cells was CD8- cells,
      whereas the ginsan induced LAK cells, were CD8+ cells. Ginsan synergized with rIL
      2 to generate LAK cells (2.0-15 fold) and the most dramatic synergy was seen at
      rIL-2 concentrations below 3 U/ml. Ginsan alone inhibited pulmonary metastasis of
      B16-F10 melanoma cells and enhanced the inhibition of lung colonies by rIL-2.
      These findings demonstrate that ginsan generates LAK cells from both NK and T
      cells through endogeneously produced multiple cytokines. This property may
      contribute to its effectiveness in the immunoprevention and immunotherapy of
      cancer.

PMID- 9525102
TI  - Hepatoprotective activity of phenylethanoids from Cistanche deserticola.
AB  - Four phenylethanoids isolated from the stems of Cistanche deserticola, acteoside
      (1), 2'-acetylacteoside (2), isoacteoside (3) and tubuloside B (4), significantly
      suppressed NADPH/CCl4-induced lipid peroxidation in rat liver microsomes.
      Addition of them to primary cultured rat hepatocytes efficiently prevented cell
      damage induced by exposure to CCl4 or D-galactosamine (D-GalN). Acteoside (1)
      further showed pronounced anti-hepatotoxic activity against CCl4 in vivo.

PMID- 9525104
TI  - Effect of ginseng saponins on exercise performance in non-trained rats.
AB  - Short-term (4 days), but not acute, treatment with ginseng saponin (GS, 10 and 20
      mg/kg/day) significantly prolonged the aerobic endurance of non-trained rats
      exercising at approximately 70% VO2max. Compared to the saline controls, GS
      treatment significantly increased the plasma free fatty acid (FFA) level and
      maintained plasma glucose level during exercise. Both the liver and skeletal
      muscle glycogen levels of the GS-treated rats were slightly higher than those of
      saline-treated controls after exhaustive exercise. These results indicate that GS
      enhances exercise endurance by altering fuel homeostasis during prolonged
      exercise, presumably by increasing FFA utilization in preference over glucose for
      cellular energy demands. To further search for the active components responsible
      for the ergogenic effect of GS, it was found that a GS preparation devoid of Rg1
      and Rb1 failed, whereas injection of either Rg1 or Rb1 enhanced aerobic exercise
      performance. These results indicate that both Rg1 and Rb1 are key ingredients in
      GS-mediated enhancement in aerobic endurance.

PMID- 9525103
TI  - Antiulcerogenic activity of trans-dehydrocrotonin from Croton cajucara.
AB  - trans-Dehydrocrotonin (DHC), the major diterpene isolated from Croton cajucara
      Benth, was assayed for antiulcerogenic activity in four induced gastric ulcer
      models in the rat. At an oral dose of 100 mg/kg DHC showed a significant
      antiulcerogenic effect on ulcers induced by hypothermic restraint stress,
      ethanol, and pylorus ligature. No significant changes in indomethacin-induced
      gastric lesions or modifications in gastric parameters such as wall mucus,
      secretion rate, pH, and total acid content were found after DHC treatment. The
      acute toxicological effects of DHC were assessed in mice. The LD50 values were
      876 mg/kg and 47.2 mg/kg for oral and intraperitoneal administrations,
      respectively. The cytotoxicity of DHC was also studied. A dose-dependent
      inhibition of cell viability was observed in V-79 fibroblast cell cultures with
      an IC50 of 240 microM. The high yields of DHC obtained from dried C. cajucara
      barks as well as its good antiulcerogenic activity and low toxicity support the
      pharmacological study of this compound as a potential new antiulcerogenic drug.

PMID- 9525105
TI  - A comparative study of the analgesic and anti-inflammatory activities of
      pectolinarin isolated from Cirsium subcoriaceum and linarin isolated from
      Buddleia cordata.
AB  - The dried aqueous extract of aerial parts of Cirsium subcoriaceum (Asteraceae)
      and its major flavonoid glycoside, pectolinarin, have been evaluated for
      analgesic and anti-inflammatory effects in mice and rats, respectively. Both the
      extract and pectolinarin exerted significant and dose-dependent analgesic and
      anti-inflammatory activities. Also, the anti-inflammatory activities of an
      aqueous extract of Buddleia cordata and its principal glycoside linarin were
      evaluated. The results of pharmacological testing proved that linarin is a better
      anti-inflammatory agent than pectolinarin and indomethacin. On the other hand,
      pectolinarin exerted a better analgesic effect than linarin.

PMID- 9525106
TI  - Silymarin inhibits the development of diet-induced hypercholesterolemia in rats.
AB  - To study the ability of silymarin, a standardized mixture of antioxidant
      flavonolignans from the medicinal plant Silybum marianum, and of silybin, the
      main flavonolignan of silymarin, to inhibit the development of diet-induced
      hypercholesterolemia the rats were fed high cholesterol diet (HCD). Silymarin or
      silybin were given as dietary supplements, and their influences on serum
      cholesterol levels were compared to those of probucol, an antioxidant
      hypocholesterolemic drug. Anticholesterolemic effect of silymarin was parallel to
      that of probucol, and dose-dependent at dietary drug concentrations of 0.1-0.5
      1.0% (w/w). However, in contradistinction to probucol, silymarin caused an
      increase in high density lipoprotein (HDL)-cholesterol and a decrease in liver
      cholesterol content, changes considered to be of benefit. In addition to its
      anticholesterolemic effect silymarin partially prevented the HCD-induced decrease
      in liver reduced glutathione, an endogenous antioxidant. Silybin was not so
      effective as silymarin suggesting that either other constituent(s) of silymarin
      may be responsible for its anticholesterolemic effect or the bioavailability of
      silybin alone might be lower than that of silybin as a compound of silymarin.

PMID- 9525107
TI  - Three new flavonoids and antiallergic, anti-inflammatory constituents from the
      heartwood of Dalbergia odorifera.
AB  - Three new flavonoids, (3R)-4'-methoxy-2',3,7-trihydroxyisoflavanone (11), 7
      methoxy-3,3',4',6-tetrahydroxyflavone (18), and 2',7-dihydroxy-4',5'
      dimethoxyisoflavone (22), were isolated from the heartwood of Dalbergia odorifera
      T. Chen. (Leguminosae), together with twenty-two known compounds, (S)-4
      methoxydalbergione (1), cearoin (2), medicarpin (3), formononetin (4), sativanone
      (5), 3-hydroxy-9-methoxy-coumestan (6), meliotocarpan A (7), isoliquiritigenin
      (8), stevein (9), liquiritigenin (10), 3',4',7-trihydroxyflavanone (12), butein
      (13), 3'-hydroxymelanettin (14), koparin (15), bowdichione (16), fisetin (17),
      melanettin (19), sulfuretin (20), 3'-hydroxydaidzein (21), 3'-O-methylviolanone
      (23), xenognosin B (24), and dalbergin (25). These flavonoids were evaluated in
      antiallergic and anti-inflammatory tests. The results showed that (S)-4
      methoxydalbergione (1) and cearoin (2) exhibited antiallergic activity while (S)
      4-methoxydalbergione (1), cearoin (2), butein (13), koparin (15), bowdichione
      (16), 3'-O-methylviolanone (23), and xenognosin B (24) showed significant anti
      inflammatory activity.

PMID- 9525108
TI  - New saponins from the seeds of Agrostemma githago var. githago.
AB  - Two new saponins were isolated from the seeds of Agrostemma githago L. var.
      githago. On the basis of chemical and spectral evidence their structures were
      determined to be 3-O-beta-D-xylopyranosyl-(1-->3)-[beta-D-galactopyranosyl-(1-
      >2)]-beta- D- glucuronopyranosylgypsogenin-28-O-beta-D-xylopyranosyl-(1-->4)-
      [beta-D-glucopyranosyl-(1-->3)]-alpha-L-rhamnopyranosyl-(1-->2)-beta- D-4-O
      acetylfucopyranoside and 3-O-beta-D-xylopyranosyl-(1-->3)- [beta-D
      galactopyranosyl-(1-->2)]-beta-D-glucuronopyranosyl-gyp sogenin- 28-O-beta-D
      xylopyranosyl-(1-->3)-beta-D-xylopyranosyl-(1-->4)- [beta-D-glucopyranosyl-(1-
      >3)]-alpha-L-rhamnopyranosyl-(1-->2)-beta-D- 4-O-acetylfucopyranoside.

PMID- 9525109
TI  - Structure-activity relationships of imperialine derivatives and their
      anticholinergic activity.
AB  - In order to check the structure-activity relationship and prepare more potent
      derivatives of imperialine with anticholinergic activity, imperialinol (2), 3
      beta-acetoxyimperialine (3), 3 beta-propionoxyimperialine (4), and 3 beta
      butyroxyimperialine (5) were prepared. Compounds 4 and 5 displayed better
      anticholinergic activity against muscarinic receptors of the heart and brain than
      imperialine (1). The decrease in activity in 2 showed the importance of the 6
      keto functionality in imparting the anticholinergic activity.

PMID- 9525111
TI  - Aloe-emodin effects on arylamine N-acetyltransferase activity in the bacterium
      Helicobacter pylori.
AB  - Arylamine N-acetyltransferase (NAT) activities with p-aminobenzoic acid (PABA)
      and 2-aminofluorene (AF) were determined in H. pylori collected from peptic ulcer
      patients. Cytosols or suspensions of H. pylori with or without different
      concentrations of aloe-emodin co-treatment showed different percentages of AF and
      PABA acetylation. The data indicate that there was decreased NAT activity
      associated with increased aloe-emodin in H. pylori cytosols. Inhibition of growth
      study from H. pylori demonstrated that aloe-emodin elicited dose-dependent growth
      inhibition in H. pylori cultures. The report is the first finding of aloe-emodin
      inhibition of arylamine NAT activity in a strain of H. pylori.

PMID- 9525112
TI  - Biological activities of synthetic triterpenoid and steroid beta-D-glucopyranosyl
      (1-->2)-alpha-D-glucopyranosides.
AB  - Comparisons of the biological activities of diosgenyl, methyl glycyrrhetinate, or
      digitoxigenyl 3-O-beta-D-glucopyranosyl-(1-->2)-alpha-D-glucopyranoside with
      those of other previously tested glycosides confirmed our assumption that both
      haemolytic and antifungal activities of steroid saponins are generally parallel
      to each other, while almost all haemolytic triterpenoid saponins have no
      antifungal activity. The earlier supposition that cardiac diglycosides having a
      (1-->4) sugar linkage have stronger activities than those with a (1-->6) linkage
      has been extended by the demonstration of reduced activity also in those with a
      (1-->2) linkage.

PMID- 9525114
TI  - AIDS Education and Training Centers fact sheet. U.S. Department of Health and
      Human Services Health Resources and Services Administration.

PMID- 9525113
TI  - Alkamides from Phyllanthus fraternus.
AB  - Two alkamides E,E-2,4-octadienamide and E,Z-2,4-decadienamide have been isolated
      from Phyllanthus fraternus, a plant used in Ghanaian traditional medicine to
      treat malaria. The compounds possess an alpha, beta, gamma, delta-unsaturated
      conjugated amide, a feature believed to enhance antiplasmodial activity. By means
      of an in vitro assay the two alkamides have been shown to possess moderate
      antiplasmodial activity.

PMID- 9525110
TI  - Cytotoxic coumarins from the aerial parts of Tordylium apulum and their effects
      on a non-small-cell bronchial carcinoma line.
AB  - Seven coumarins were isolated from the aerial parts of Tordylium apulum; their
      structures were established by spectroscopic means. All compounds were tested in
      vitro for their cytotoxicity against two cell line systems. The antiproliferative
      effects for three of them were studied at the level of the cell cycle in
      asynchronous cells of the NSCLC-N6 line with a flow cytometry apparatus.

PMID- 9525115
TI  - 4 key elements of a successful recall system.

PMID- 9525116
TI  - Orthodontic bonding.

PMID- 9525117
TI  - Risk and prevention of occupational exposures to blood in dentistry.

PMID- 9525118
TI  - Commonly asked questions about nightguard vital bleaching.
AB  - There are three basic classes of materials and techniques used for the bleaching
      of vital teeth. These include the in-office bleaching technique with 35 percent
      hydrogen peroxide, the Nightguard vital bleaching technique with 10 percent
      carbamide peroxide, and the over-the counter bleaching kits with three-to-six
      percent hydrogen peroxide. The most popular of these techniques is Nightguard
      vital bleaching also referred to as dentist-prescribed, home-applied bleaching.
      This article looks at the current status of the Nightguard vital bleaching
      technique, with a special emphasis on the clinical aspects of the treatment,
      along with the most commonly asked questions concerning the procedure. It would
      still appear that this form of dentist-prescribed, home-applied bleaching, when
      preceded by a proper examination and correct diagnosis, applied with a properly
      fitted prosthesis, and monitored as needed by a dentist, is as safe as other
      accepted dental procedures or commonly ingested foodstuffs.

PMID- 9525119
TI  - The dental assistant's management of medical emergencies.

PMID- 9525120
TI  - Smokeless tobacco: intervention techniques for the dental professional.

PMID- 9525121
TI  - Check your dental unit water IQ.

PMID- 9525122
TI  - Acid etching and dental adhesive systems.

PMID- 9525123
TI  - Vacillate or vaccinate.

PMID- 9525125
TI  - Health and safety training for dental professionals.

PMID- 9525124
TI  - Is your OSHA compliance program up to date?
AB  - OSHA safety inspections in dental offices have decreased dramatically over the
      past several years. But this development does not mean that compliance with
      safety regulations is no longer mandatory. Recent changes and some additions to
      the OSHA regulations should serve as a catalyst to review and update your office
      safety program. This article highlights the new standards and proposes a plan for
      such a review.

PMID- 9525126
TI  - Backflow prevention and the dental unit.

PMID- 9525127
TI  - Dental assisting for the medically compromised patient.

PMID- 9525128
TI  - Improve transition with an implant conversion prosthesis for the edentulous arch.

PMID- 9525129
TI  - Alternative methods for repositioning of the inferior alveolar neurovascular
      bundle.

PMID- 9525131
TI  - An exquisite periodontal approach: flap designs for the insertion and recovery of
      root-form implants.

PMID- 9525130
TI  - Evaluating and maintaining passively fitting frameworks in implant dentistry.

PMID- 9525132
TI  - Biomechanics: the keystone of treatment planning in osseointegration.

PMID- 9525133
TI  - Root-form implant placements within the posterior mandible: a surgical approach.

PMID- 9525134
TI  - Current concerns and approaches: bridging the gap between research and clinical
      principles.

PMID- 9525135
TI  - When and how to use fixed/cemented prostheses on root-form implants.

PMID- 9525136
TI  - Bone regeneration techniques vis-a-vis dental implant procedures.

PMID- 9525137
TI  - Another approach to preparing the edentulous premaxilla for insertion of root
      form implants.

PMID- 9525138
TI  - Retention of teeth and placement of implants in the partially edentulous maxilla:
      the decision-making process.

PMID- 9525139
TI  - The mandatory inclusion of the laboratory technician in the implant team.

PMID- 9525140
TI  - State-of-the-art instrumentation allows clinicians to assess implant integration
      more accurately.

PMID- 9525141
TI  - Techniques and criteria for retention of teeth and placement of implants in the
      partially edentulous maxilla.

PMID- 9525142
TI  - When to use resorbable or non-resorbable membranes in concert with root-form
      implants.

PMID- 9525143
TI  - Inferior alveolar nerve repositioning: is there cause for concern?

PMID- 9525144
TI  - Implant prosthodontic update: the UCLA abutment; screw retention.

PMID- 9525145
TI  - Inferior alveolar nerve repositioning: is there cause for concern?

PMID- 9525147
TI  - Non-resorbable-membrane-assisted bone regeneration: stabilization and the
      avoidance of micromovement.

PMID- 9525148
TI  - The paramount role of transitional prostheses within implant prosthodontics--Part
      I.

PMID- 9525146
TI  - Practical clinical applications of implant biomechanics: alignment, torque,
      precision, set screws.

PMID- 9525149
TI  - Non-resorbable-membrane-assisted bone regeneration: microscrews, microplates, and
      reinforcement--Part II.

PMID- 9525150
TI  - Provisionalization in implant prosthodontics for the partially edentulous arch-
      Part II.

PMID- 9525151
TI  - Handling complications associated with implant surgical procedures--Part I.

PMID- 9525152
TI  - Prosthodontics, periodontics, and orthodontics: a multidisciplinary approach to
      implant dentistry--Part I.

PMID- 9525153
TI  - Handling complications associated with implant surgical procedures--Part II.

PMID- 9525154
TI  - Handling narrow ridges for insertion of root-form implants: multiple-tooth
      edentulism.

PMID- 9525155
TI  - A multidisciplinary approach to implant dentistry: prosthodontics, periodontics,
      orthodontics--Part II.

PMID- 9525156
TI  - Bone regeneration for select root-form implant sites.

PMID- 9525157
TI  - Methods and materials for provisionalization in implant prosthodontics--Part I.

PMID- 9525158
TI  - Facilitating implant placement with chin grafts as donor sites for maxillary bone
      augmentation--Part I.

PMID- 9525159
TI  - Methods and materials for provisionalization in implant prosthodontics--Part II.

PMID- 9525160
TI  - Chin grafts as donor sites for maxillary bone augmentation--Part II.

PMID- 9525161
TI  - A thorough pre-treatment evaluation format for the implant team.

PMID- 9525162
TI  - Surgical guides, off-axis reconstruction, and the use of custom abutments--Part
      I.

PMID- 9525163
TI  - Mini-implants as adjuncts for transitional prostheses.

PMID- 9525164
TI  - Conservative osteotomy technique with simultaneous implant insertion.

PMID- 9525165
TI  - Current radiographic techniques that complement implant dentistry--Part II.

PMID- 9525166
TI  - Harvesting bone for sinus-lift procedures: localization and placement.

PMID- 9525167
TI  - The impact of occlusion on implants and implant componentry--Part I.

PMID- 9525168
TI  - High-density PTFE membranes: uses with root-form implants.

PMID- 9525169
TI  - Occlusion: its impact on implants and implant componentry--Part II.

PMID- 9525170
TI  - Micromovement prevention: immobilizing by membrane tacking.

PMID- 9525171
TI  - The ultimate in soft-tissue customization.

PMID- 9525172
TI  - Know when to use wide-bodied implants to limit bone stress.

PMID- 9525173
TI  - Staged osteotomies in sinus areas: preparing for implant placement.

PMID- 9525174
TI  - The relevance of statistics to the implant clinician--Part I.

PMID- 9525175
TI  - The implant overdenture and designated attachments--the mandible.

PMID- 9525176
TI  - Surgical guides, off-axis reconstruction, and the use of custom abutments--Part
      II.

PMID- 9525177
TI  - Prosthodontic prescriptions for mandibular implant overdentures--Part I.

PMID- 9525178
TI  - Intraoral photography and videography: communicative roles in implant dentistry-
      Part I.

PMID- 9525179
TI  - Making sense of the numbers: the relevance of statistics to the implant clinician
      -Part II.

PMID- 9525180
TI  - The phenomenon of natural root intrusion in combined root-form implant cases.

PMID- 9525181
TI  - Intraoral photography and videography: communicative roles in implant dentistry-
      Part II.

PMID- 9525183
TI  - Immediate loading of implants: an improved treatment for the elderly.

PMID- 9525182
TI  - Prosthodontic prescriptions for mandibular implant overdentures--Part II.

PMID- 9525184
TI  - A protocol for timely loading of threaded implants.

PMID- 9525185
TI  - Team approach to implant dentistry: how should it work? (Part I)

PMID- 9525187
TI  - Current radiographic techniques that complement implant dentistry--Part I.

PMID- 9525188
TI  - Making sense of the numbers: the relevance of statistics to the implant clinician
      -Part III.

PMID- 9525189
TI  - The laminar bone sheet: uses with implant procedures.

PMID- 9525190
TI  - Legal implications of a medical history.

PMID- 9525191
TI  - Dentistry in China.

PMID- 9525192
TI  - Haiti. A revolution in the making.

PMID- 9525193
TI  - Disclosing your mistakes to patients: a legal perspective.

PMID- 9525194
TI  - Dentists, malpractice and not knowing enough: legal liability for failing to keep
      up with the profession.
AB  - The law imposes an obligation on you to keep current with the developments of
      your profession, particularly those developments which directly affect the health
      of your patients. From a legal perspective, you risk liability when your
      professional inquisitiveness and awareness falls below that of the reasonable
      specialist. While there is a substantial risk of being overwhelmed by the
      explosion of new dental knowledge, the alternative of being sued for malpractice
      is less attractive.

PMID- 9525195
TI  - A model for the future.

PMID- 9525196
TI  - Casting a wide net for wisdom.

PMID- 9525197
TI  - Trouble on the line: your most misunderstood and misused marketing tool.

PMID- 9525198
TI  - Answering the call to success.

PMID- 9525199
TI  - Threatened with a suit? Here's what you can do.

PMID- 9525200
TI  - Managing for success.

PMID- 9525201
TI  - Life on the red line.

PMID- 9525202
TI  - Finding a compatible consultant.

PMID- 9525203
TI  - Ask, don't tell. How to be high touch, as well as high tech.

PMID- 9525204
TI  - Internal marketing for cosmetic dentistry.

PMID- 9525205
TI  - Laser marketing.

PMID- 9525206
TI  - Disability insurance--a professional viewpoint.

PMID- 9525207
TI  - The dental marketing index: where do you fit in?

PMID- 9525208
TI  - Causes and remedies for broken appointments.

PMID- 9525209
TI  - Beware the hollow middle.

PMID- 9525210
TI  - Motivation by video: it works!

PMID- 9525211
TI  - Ten steps you must take to retain (or regain) control of your dental practice.

PMID- 9525212
TI  - Blending individual strengths for team success.

PMID- 9525213
TI  - So you've decided to computerize. Now what?

PMID- 9525214
TI  - Why do patients sue?

PMID- 9525215
TI  - Do's and dont's. A guide to improving patient relations.

PMID- 9525216
TI  - Showing the way. How to lead your practice from 'pretty good' to 'great'!

PMID- 9525217
TI  - Planning ahead for the sale of your practice.

PMID- 9525219
TI  - Team business systems. Means and methods.

PMID- 9525218
TI  - Make your practice grow with a "Hygiene Friday".

PMID- 9525220
TI  - Won't your mommy and daddy be proud?

PMID- 9525221
TI  - Increase case acceptance with effective communication skills.

PMID- 9525222
TI  - The top 3 reasons people leave your practice.

PMID- 9525223
TI  - Rightsizing downsizing restructuring.

PMID- 9525224
TI  - Ten things I'd never put up with if I were a dentist.

PMID- 9525225
TI  - Walking the technological tightrope.

PMID- 9525226
TI  - Spouses in practices ... do they belong?

PMID- 9525227
TI  - Handling the unkindest cut of all.

PMID- 9525228
TI  - Getting real about your ideal practice.

PMID- 9525229
TI  - High-tech to buy or not to buy.

PMID- 9525230
TI  - Dentistry is a business too!

PMID- 9525231
TI  - Scheduling for a stress-free day.

PMID- 9525232
TI  - Credit and collection.

PMID- 9525233
TI  - How to keep managed care from nibbling away your fee-for-service practice.

PMID- 9525234
TI  - Empower the team delegate.

PMID- 9525235
TI  - Communicating ... it's simple.

PMID- 9525237
TI  - The electrical storm.

PMID- 9525236
TI  - Nurture personal referrals--your best source of new patients.
AB  - In your morning meetings, identify those patients who would be a great person to
      ask for a referral--patients who have expressed pleasure in receiving treatment
      from you. Then, determine who is going to ask for that referral. You wouldn't
      want to have EVERY-ONE ask them for a referral, so give someone that
      responsibility. Be sure that you have done some role playing and have practiced
      the verbal skills of "asking" for a referral. Get comfortable asking. Know that
      you will never know what you will get unless you ASK!!! All good businesses ask
      for referrals from their best customers. Learn from the masters. Pattern your own
      behavior after those who have acquired admirable results. When you identify
      patients who have accepted and have been pleased with your treatment, have come
      to their appointments on time, have gladly paid their bills, and have been a joy
      to treat, ASK these folks for a referral. More than likely they will refer others
      to you who are of like character. You can build a practice "on good patients just
      like you" and expect that to happen!!! Together, as a team, develop ways of
      acknowledging and nurturing your referral sources. If these wonderful people
      provide 70+ percent of your new patients, it benefits you to invest time and
      money in maximizing this source of practice growth.

PMID- 9525238
TI  - Binaural application of the bone-anchored hearing aid.
AB  - Most, but not all, hearing-impaired patients with air conduction hearing aids
      prefer binaural amplification instead of monaural amplification. The binaural
      application of the bone conduction hearing aid is more disputable, because the
      attenuation (in decibels) of sound waves across the skull is so small ( 10 dB)
      that even one bone conduction hearing aid will stimulate both cochleas
      approximately to the same extent. Binaural fitting of the bone-anchored hearing
      aid was studied in three experienced bone-anchored hearing aid users. The
      experiments showed that sound localization, and speech recognition in quiet and
      also under certain noisy conditions improved significantly with binaural
      listening compared to the monaural listening condition. On the average, the
      percentage of correct identifications (within 45 degrees ) in the sound
      localization experiment improved by 53% with binaural listening; the speech
      reception threshold in quiet improved by 4.4 dB. The binaural advantage in the
      speech-in-noise test was comparable to that of a control group of subjects with
      normal hearing listening monaurally versus binaurally. The improvements in the
      scores were ascribed to diotic summation (improved speech recognition in quiet)
      and the ability to separate sounds in the binaural listening condition (improved
      sound localization and improved speech recognition in noise whenever the speech
      and noise signals came from different directions). All three patients preferred
      the binaural bone-anchored hearing aids and used them all day.

PMID- 9525239
TI  - Rate of gas exchange in the middle ear of guinea pigs.
AB  - Gas exchange between blood in the middle ear (ME) mucosa and ambient ME gas may
      be limited by diffusion through tissue or blood perfusion. In order to study the
      limiting factors in ME gas exchange, a hole was drilled in the bulla of 14
      anesthetized guinea pigs through which a mass spectrometer probe was inserted and
      sealed in place. The rate at which oxygen (O2), carbon dioxide (CO2), nitrogen,
      and argon concentrations changed toward their steady state values was recorded.
      From the exponential fitted curves, gas rate constants (Kg) were calculated. The
      ratio KCO2/KO2 was 4:1, which is lower than expected from a diffusion-limited
      process in an aqueous compartment. The different rate ratios of CO2 and O2
      indicate a diffusion-limited process. However, the deviation of the KCO2/KO2
      ratio from that expected in aqueous solutions may indicate the involvement of a
      lipid compartment in gas exchange or other physiological mechanisms such as local
      acidity.

PMID- 9525240
TI  - Expression of acute otitis media after receptor blockade of platelet activating
      factor, thromboxane, and leukotrienes in the chinchilla.
AB  - To determine the role of inflammatory products of phospholipid metabolism in
      acute otitis media (AOM), we infected 128 chinchillas with Streptococcus
      pneumoniae and randomly assigned them to one of four equal-sized treatment groups
      receiving intramuscular ampicillin sodium (control) or intramuscular ampicillin
      plus receptor blockers of platelet activating factor (WEB 2086, 5 mg/d orally),
      of leukotriene (MK 571, 0.5 mg/d orally), or of thromboxaneA2 (GR 32191B, 5 mg/d
      orally). All treatments were begun on day 2 postinoculation and continued for 10
      days. On days 3, 6, 9, and 12, 8 animals from each group were sacrificed.
      Effusions were recovered for biochemical assay, and the right middle ears were
      prepared for histologic study. Differences among groups in the number of ears
      with effusion or in effusion volume were not statistically significant. In
      comparison to the control group, mucosal thickness and the number of ears with
      histopathologic signs of inflammation were significantly less in the GR and WEB
      treatment groups, but not the MK group. Also, effusion concentrations of free
      fatty acids, protease, and hydrolytic enzymes were significantly less in those
      groups. These results show that the addition of a receptor blocker for either
      platelet activating factor and/or thromboxane to ampicillin in the treatment of
      AOM reduces mucosal inflammation and decreases the production of other
      inflammatory chemicals. The failure of a receptor blocker of leukotrienes to
      moderate disease expression suggests either a less important role for these
      chemicals in AOM or an insufficient bioavailability of the specific MK 571
      inhibitor. These results confirm that platelet activating factor and thromboxane
      are active mediators of inflammation in AOM.

PMID- 9525241
TI  - Fiber grouping in the feline vestibular nerve before and after labyrinthectomy.
AB  - The vestibular nerve is composed of fibers with a wide spectrum of diameters. The
      fibers of largest diameter are known to innervate the type I hair cells of the
      cristae, while the small-diameter fibers innervate the type II hair cells.
      Midsized fibers (dimorphic fibers) represent neurons that innervate both type I
      and type II hair cells. Reports by others have commented on the tendency for
      clustering of fibers with like diameters. Rigorous statistical proof for or
      against clustering has not yet been presented. The explanation for this is, in
      part, the mathematic complexity of analyzing clustering in a system composed of
      three elements. We report a new method for analysis of fiber clustering and apply
      this method to large-, medium-, and small-diameter fibers in the feline
      vestibular nerve. The fiber grouping in the caudal and rostral ends of the
      vestibular nerves of six normal animals is compared to that in similar areas of
      the nerves of five animals 12 to 17 months after unilateral labyrinthectomy. No
      statistically significant clustering of fiber types was found in the rostral
      portion of either the control or the labyrinthectomized animals. In the caudal
      portion of the control nerves, clustering of the large fibers was demonstrated (p
      < .005, chi2 test). This clustering was not demonstrated after labyrinthectomy.
      An explanation of these findings is discussed. The method used in this study to
      analyze fiber clustering may be applicable to other nerve systems of greater
      complexity.

PMID- 9525242
TI  - Increase of mucous glycoprotein secretion by tumor necrosis factor alpha via a
      protein kinase C-dependent mechanism in cultured chinchilla middle ear epithelial
      cells.
AB  - Tumor necrosis factor alpha (TNF-alpha), originally defined by its antitumoral
      activity, is now recognized as a polypeptide mediator of inflammatory and
      cellular immune response. Recent studies have demonstrated that TNF-(alpha exists
      in the fluid of otitis media with effusion and, therefore, suggested its possible
      role in the pathogenesis of mucus hypersecretion. In this study, the effects of
      TNF-alpha on mucous glycoprotein (MGP) secretion from cultured chinchilla middle
      ear epithelial cells were examined, and TNF-alpha was found to stimulate MGP
      secretion in a time- and concentration-dependent manner. The action of TNF-alpha
      on MGP secretion was significantly and dose-dependently inhibited by TNF-alpha
      monoclonal antibody; this finding is suggestive of its specificity on MGP
      secretion. The addition of the protein kinase C inhibitor 1-(5
      isoquinolinylsulfonyl)-2-methylpiperidine (H-7) to the culture significantly
      blocked TNF-alpha-induced MGP secretion, while the calmodulin inhibitor N-(6
      aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) did not. This suggests that
      TNF-alpha stimulates MGP secretion via a protein kinase C-dependent mechanism.

PMID- 9525243
TI  - Development of cochlear sensitivity to aminoglycoside antibiotics.
AB  - This study examined the temporal relationship between aminoglycoside ototoxicity
      and the onset of auditory function in the rat. A single dose of gentamicin
      sulfate (200 mg/kg) and furosemide (100 mg/kg) was administered on postnatal day
      6 (P6), P7, P8, P9, or P10, just before the onset of auditory function.
      Ototoxicity was assessed by the elevation of auditory brain stem response (ABR)
      thresholds, recorded once the rats had matured. The ABRs were evoked by acoustic
      clicks and tone pips. The thresholds of control and P6- and P7-treated animals
      did not differ significantly from each other. Thresholds of some P8- and all P9
      treated animals were elevated. The P10-treated animals were deafened, according
      to these ABR criteria. These data suggest that the potential for aminoglycoside
      ototoxicity develops rapidly between P8 and P10, just before the onset of
      auditory function.

PMID- 9525244
TI  - Systematic analysis of snoring in women.
AB  - Nineteen percent of women are habitual snorers, yet most snoring studies report
      only on male snorers. The aim of this study was to identify the factors
      responsible for habitual snoring in women. Twenty-four snorers and 16 controls
      were studied prospectively in a special snoring clinic. Snorers were shorter (p =
      .005) and heavier (p = .001), and with greater body mass index (BMI: p < .001),
      collar size (p = .002), and submental skinfold thickness (p = .001) than
      controls. The area of the posterior pharyngeal wall visible on oral examination
      was smaller in snorers (p = .005). Acoustic rhinometry areas and volumes were
      similar in the two groups. Nasal flow-volume loops showed reduced expiratory (p =
      .01) and inspiratory (p = .07) flow in snorers. Inspiratory flow correlated
      inversely with nasal symptoms (p < .05). The factors that best predict habitual
      snoring in women are a high BMI, a high nasal symptom score, and heavy weight. Of
      these, BMI is the most powerful.

PMID- 9525245
TI  - Evidence of potential regulation by interleukin-4 of the soluble intercellular
      adhesion molecule 1 level in patients with seasonal allergic rhinitis under
      provocation by a small amount of natural allergen.
AB  - Interleukin-4 (IL-4) and intercellular adhesion molecule 1 (ICAM-1) are assumed
      to be involved in the pathogenesis of allergic disease. In this study, we
      examined the potential link between IL-4 and soluble ICAM-1 (sICAM-1) levels in
      patients with allergic rhinitis. The levels of sICAM-1 and IL-4 in sera and in
      nasal epithelial lining fluids (ELF) from 12 patients with Japanese cedar
      pollinosis were measured preseason through postseason, and the results were
      compared with those from 7 healthy subjects. In sera from the allergic subjects,
      the levels of sICAM- 1 were upregulated during the early part of the season and
      downregulated during the middle of the season, with upregulation of the IL-4
      levels. Moreover, a negative correlation was found between the serum sICAM-1
      levels and serum IL-4 levels during the middle (r = -.80) and late (r = -.73)
      parts of the season. In ELF from allergic subjects, the levels of sICAM-1 were
      significantly upregulated during the early and middle parts of the season, and
      began to be downregulated during the late part of the season, with upregulation
      of the levels of IL-4. In conclusion, IL-4 possibly acts as a potential
      suppressor of sICAM-1 in the pathogenesis of seasonal allergic rhinitis, at least
      under provocation by a small amount of natural allergen.

PMID- 9525246
TI  - Transient vocal fold immobility.
AB  - Temporary vocal fold immobility resolving in 4 weeks or less is considered a
      transient immobility. Many different disorders may lead to this type of laryngeal
      motion impairment. It is important for otolaryngologists to be familiar with the
      differential diagnosis for transient vocal fold immobility in order to optimize
      the management of these unusual cases.

PMID- 9525247
TI  - Laser-induced fluorescence imaging in localization of head and neck cancers.
AB  - Laser-induced fluorescence tumor imaging exploits the difference in tissue
      autofluorescence properties between normal and cancerous tissues. The
      effectiveness and reliability of fluorescence imaging with a lung imaging
      fluorescence endoscopy (LIFE) system for cancers in the head and neck were
      compared to those of white light endoscopy (WLE). Examinations by WLE and LIFE
      were conducted on 25 patients suspected for malignancy. Histologic diagnosis was
      confirmed by biopsy. Posttreatment evaluations were performed on 6 cancer
      patients identified by this study. By LIFE, all 16 cancerous lesions, including 2
      occult cancers, were identified (100%), while WLE achieved only an 87.5%
      detection rate. LIFE (specificity 87.5%) was greatly helpful to WLE (specificity
      50%) in differentiating inflammation from malignancy, though it failed to exclude
      granuloma. The results of this study suggest potential roles of LIFE in early
      detection, correct staging, and treatment evaluation of cancers in the head and
      neck.

PMID- 9525248
TI  - Routine hospital admission for patients undergoing upper aerodigestive tract
      endoscopy is unwarranted.
AB  - Although upper aerodigestive tract endoscopy is commonly performed, the need for
      hospital admission remains controversial. A retrospective review of endoscopy
      performed between January 1, 1993, and June 30, 1995, identified 201 patients who
      underwent 371 procedures. Complications occurred in 34 of 371 (9.2%) procedures
      in 26 of 201 (12.9%) patients. Of these, 11 of 371 (3.0%) were major (requiring
      admission for management) and 23 of 371 (6.2%) were minor. For multiple
      concurrent procedures, the overall complication rate was 19.3% (22/114); 5.3%
      (6/114) were major and 14.0% (16/114) were minor. All 8 patients (100%) who went
      on to have major complications and 24 of the 26 (92.3%) who went on to have any
      complication were successfully identified prior to discharge; 2 required
      postdischarge outpatient management of urinary retention. Five statistically
      significant risk factors for complication were identified: preexisting cardiac
      conditions, American Society of Anesthesiologists rating, airway class rating,
      anesthesia type, and number of endoscopic procedures performed. A comparison of
      various approaches to hospital admission demonstrated that selective admission
      based on clinical judgment was superior to routine admission of all patients. In
      conclusion, we recommend that upper tract endoscopy be performed on an ambulatory
      basis because 1) the complication rate is low, 2) complications requiring
      inpatient management are identifiable in the immediate postoperative period, and
      3) of the approaches to hospital admission examined, it was the most economical.

PMID- 9525249
TI  - Electrosurgery in the head and neck.
AB  - Electrosurgery is widely used in the practice of otolaryngology-head and neck
      surgery. Despite its popularity, few training programs give formal education in
      the optimal use of electrosurgical instruments. This article reviews the history,
      physics, and tissue effects of these commonly used devices. Armed with this
      knowledge, the head and neck surgeon can take full advantage of electrosurgery's
      ability to dissect tissues with precision and minimal blood loss.

PMID- 9525250
TI  - Giant tonsillolith.

PMID- 9525251
TI  - Hamartoma of the larynx: a critical review of the literature.
AB  - Hamartoma of the larynx is an extremely rare lesion, and the number of well
      documented and acceptable cases is limited. The world literature is critically
      reviewed in order to develop a more accurate clinicopathological profile of this
      tumorlike malformation, which has to be differentiated from choristoma, teratoma,
      and rhabdomyoma, among others. Management consists of local excision, and the
      prognosis is good.

PMID- 9525252
TI  - The signal model: a possible explanation for the conversion of DNA double-strand
      breaks into chromatid breaks.
AB  - PURPOSE: To present and evaluate the 'signal' model for the formation of
      radiation-induced chromatid breaks. CONCLUSIONS: Chromatid breaks in human cells
      represent the apparent interstitial loss of up to about 40 Mbp of DNA, difficult
      to account for as single lesions under the classical 'breakage-and-reunion'
      hypothesis. If breakage-first resulted from two interacting DNA double-strand
      breaks (dsb) with the loss or displacement of the intervening fragment, a dose
      squared relationship would be predicted for chromatid breaks. However, the
      relationship between chromatid break frequency and dose for human cells is
      linear. The alternative 'exchange' model of Revell is based on the principle of
      the interaction of two initiating lesions, thus also predicting a dose-squared
      relationship for chromatid 'breaks'. The signal model explains the conversion of
      dsb into chromatid breaks on the assumption that a single dsb generates a signal
      which triggers the cell to initiate a recombinational exchange involving a large
      loop of chromatin. Incomplete exchanges would be observed as chromatid breaks.
      Possible candidates for the signalling molecule(s) are DNA protein kinase (DNA
      PK) and the ATM protein.

PMID- 9525254
TI  - Chromosome aberration frequencies in human lymphocytes irradiated in a phantom by
      a mixed beam of fission neutrons and gamma-rays.
AB  - PURPOSE: To provide further information on the existence of a significant
      quadratic component of the dose response relationship for the production of
      dicentrics in human lymphocytes by mixed fission neutron and gamma-ray
      irradiation, which has been observed previously employing the same beam under
      free-in-air conditions. MATERIALS AND METHODS: Irradiation of blood samples and
      dosimetry was performed at 2 cm depth in a polymethyl methacrylate (PMMA) phantom
      of 16 cm side-length where the PMMA material fully surrounded the blood specimen.
      Chromosome analysis was carried out exclusively in complete first division
      metaphases. RESULTS: Dicentric yields induced by absorbed doses between 0.043 and
      2.68 Gy fit a linear-quadratic model with a quadratic coefficient significantly
      different from zero. The distribution of dicentrics is overdispersed compared to
      Poisson at lower doses, but is poissonian at higher doses. CONCLUSION: The
      presence of a significant quadratic dose response coefficient for dicentrics,
      both for free-in-air and phantom irradiation, is caused by the various degraded
      fission spectra that produce neutrons or recoil protons over a broad energy
      range, rather than by the gamma-ray component of the beam.

PMID- 9525253
TI  - The effect of track structure on the induction of chromosomal aberrations in
      murine cells.
AB  - PURPOSE: To measure chromosome aberrations in C3H 10T1/2 mouse fibroblasts using
      FISH painting at the first mitosis following exposure to 30 keV/microm hydrogen
      or neon ions. MATERIALS AND METHODS: Cells in plateau-phase were irradiated with
      0.86 MeV protons at the TTT-3 Tandem accelerator in Naples (Italy), or with 400
      MeV/n Ne ions at the HIMAC accelerator in Chiba (Japan). Colcemid-blocked cells
      were harvested at the first mitosis following exposure, and chromosome spreads
      were hybridized in situ with a fluorescein-labelled composite mouse DNA probe
      specific for chromosomes 2 and 8. RESULTS: Protons were more efficient than neon
      ions at the same LET in the induction of chromosome interchanges and breaks.
      Yields of complex exchanges were similar for both particles at the same dose, but
      protons produced mostly insertions, while with Ne exposure non-reciprocal
      exchanges were the most frequent complex-type exchange. CONCLUSIONS: Charged
      particles with the same LET produce different yields of chromosome aberrations,
      and some observed differences can be explained based on the available track
      structure models.

PMID- 9525255
TI  - Correlation between cellular radiosensitivity and non-repaired double-strand
      breaks studied in nine mammalian cell lines.
AB  - PURPOSE: To test the relationship between cell killing and non-repaired DNA
      strand breaks both in repair proficient and deficient cell lines. MATERIALS AND
      METHODS: Five of the cell lines used are repair competent (CHO, CHO K1, rat
      rhabdomyosarcoma R1H, mouse balb and normal human fibroblasts), while four
      display a reduced repair capacity (scid, xrs1, xrs5, AT). Cell survival was
      determined by colony formation assay. The total number of strand breaks was
      measured by the alkaline unwinding technique and the numbers of double-strand
      breaks by constant-field gel electrophoresis. RESULTS: The nine cell lines showed
      a broad spectrum in radiosensitivity with SF2 values ranging from 0.018 to 0.58.
      The cell lines did not vary in the number of induced strand breaks, neither for
      all strand breaks nor for double-strand breaks alone. In contrast, there was a
      large variation in the number of non-repaired strand breaks measured 24 h after
      irradiation. Comparison of cell killing with the number of non-repaired breaks
      measured after a dose of 90 Gy showed no correlation for single-strand breaks
      (r2=0.29) but a fairly good correlation for double-strand breaks (r2=0.87). This
      correlation was found to hold both for repair proficient and deficient cell
      lines. CONCLUSIONS: The results obtained strongly suggest that the number of non
      repaired double-strand breaks measured 24h after irradiation can be used as an
      indicator of cellular radiosensitivity.

PMID- 9525256
TI  - Radiation-induced micronucleus formation in human skin fibroblasts of patients
      showing severe and normal tissue damage after radiotherapy.
AB  - PURPOSE: Treatment schedule and total dosage in radiation therapy is based on the
      tumoricidal doses and the tolerance dose of the perifocal normal tissue. Since
      large-scale variations occur between the patients concerning the side effects,
      one of the major goals of radiation research recently has been the development of
      a predictive in vitro assay. This paper is a contribution to that effort.
      MATERIALS AND METHODS: Skin fibroblasts of patients with normal-tissue reactions
      or acute and/or late increased side effects and cell lines of four individuals
      carrying the heritable disease ataxia telangiectasia were irradiated in vitro.
      The formation of micronuclei was chosen as biological endpoint and the results
      were compared with the clinically observed side effects. RESULTS: In general, a
      radiation dose-dependent increase in micronucleus frequency was found. The cells
      of the majority of the sensitive patients, as well as those of homozygous and
      heterozygous ataxia telangiectasia individuals, showed a higher micronucleus
      induction than the average of the donors with normal sensitivity. CONCLUSIONS:
      The micronucleus test seems to be a very promising tool in the evaluation of
      radiation sensitivity prior to therapy. However, larger studies are needed to
      confirm these findings and to optimize the methodology, and it is presumed that a
      final predictive assay will consist of a combination with other test systems.

PMID- 9525257
TI  - Apoptosis induced by fast neutrons versus 60Co gamma-rays in human peripheral
      blood lymphocytes.
AB  - PURPOSE: To investigate the effectiveness of high LET fast neutrons compared with
      low LET 60Co gamma-rays to induce apoptosis in resting lymphocytes. MATERIALS AND
      METHODS: Apoptosis induction was quantified by light microscopic analysis of
      irradiated lymphocyte samples from healthy donors after 24 h culture. For the
      dose-response analyses doses ranging from 0.05 to 5 Gy were applied at 1.5 Gy/min
      (gamma-rays) or 0.2 Gy/min (fast neutrons). To investigate the role of DNA repair
      in apoptosis induction a dose of 2 Gy was also given at low dose-rate (0.006
      Gy/min). RESULTS: Dose-response curves obtained with both radiation qualities
      were characterized by an initial steep increase in the number of apoptotic cells
      below 1 Gy, with a flattening of the curves at higher doses towards 5 Gy. The
      calculated relative biological effectiveness (RBE) values for fast neutrons were
      close to unity. When a 2 Gy dose was administered at low rather than high dose
      rate no decrease in apoptotic cell yield was observed. CONCLUSION: The dose
      response data confirm the high radiosensitivity of lymphocytes and demonstrate
      that their response to undergo early interphase cell death by apoptosis is
      largely independent of LET. The observations that apoptosis induction is
      independent of LET and dose-rate may suggest that initial DNA damage, as opposed
      to DNA repair, dominate the induction of apoptosis in resting lymphocytes.

PMID- 9525258
TI  - Simultaneous evaluation of radiation-induced apoptosis and micronuclei in five
      cell lines.
AB  - PURPOSE: This study was conducted to clarify the relationship among the
      frequencies of micronuclei (MN) and apoptosis, and clonogenic cell survival after
      irradiation. MATERIALS AND METHODS: The frequencies of MN and apoptosis were
      compared in the surviving fraction in three human tumour cell lines and two
      rodent cell lines at various irradiation doses. RESULTS: The SHIN-3, DU-145 and
      CHO-K1 cells showed dose-dependent increases of MN per binucleate cell and an
      excellent correlation between the MN frequency and surviving fraction after
      irradiation. The F9 and COLO 320DM cells did not show this correlation. The
      number of apoptotic cells increased according to the increase in radiation dose
      in the F9 and COLO 320DM cells, but not in the SHIN-3, DU-145 or CHO-K1 cells.
      CONCLUSIONS: The detection of the MN frequency alone is insufficient to measure
      cellular intrinsic radiosensitivity. The simultaneous use of the MN assay and the
      detection of apoptotic cells would be more reliable as a method for predicting
      cell survival after radiation.

PMID- 9525259
TI  - Inactivation of C3H10T1/2 cells by low energy protons and deuterons.
AB  - PURPOSE: To determine the RBE-LET relationship for C3H10T1/2 cell inactivation by
      protons in the LET range 11-33 keV/microm and to compare inactivation frequencies
      induced in C3H10T1/2 cells by protons and deuterons at two matching LET values in
      the range 11-20 keV/microm. MATERIALS AND METHODS: C3H10T1/2 cells were
      irradiated with protons and deuterons at the radiobiological facility set up at
      the 7MV Van de Graaff accelerator at the LNL, Legnaro, Padova. Gamma rays from
      60Co were used as reference radiation. RESULTS: Proton RBE values
      (alpha/alphagamma) for inactivation of C3H10T1/2 cells are constant around a
      value of 2 between 11 and 20 keV/microm and then rise sharply to reach a value of
      4.2+/-1.0 at 33 keV/microm. Deuteron RBE values are 1.7+/-0.4 and 2.2+/-0.6 at
      LET values of 13 and 18 keV/microm respectively. CONCLUSIONS: Proton RBE values
      with C3H10T1/2 cells are significantly larger than unity at LET values as low as
      11 keV/microm. No difference in effectiveness for inactivation of C3H10T1/2 has
      been found between protons and deuterons at two LET values in the range 10-20
      keV/microm.

PMID- 9525260
TI  - The effects of 2-deoxyglucose and amino-oxyacetic acid on the radiation response
      of mammalian cells in vitro.
AB  - Cells use substrates such as glucose and glutamine to provide energy for repair
      of radiation damage. Glutaminolysis and glycolysis were inhibited by
      aminooxyacetic acid (AOAA) and 2-deoxyglucose (2DG), respectively, to inhibit
      metabolism of these substrates in order to determine the effect on radiation
      response of CHO-K1 cells in vitro. Exposure to treatments which inhibit energy
      metabolism resulted in alterations in radiosensitivity and, in general, a
      reduction in cellular recovery rate after y-irradiation but varied with regard to
      the extent of recovery. The greatest inhibition of recovery relative to that in
      normal culture medium was found with medium which lacked glucose and glutamine
      and contained 2DG and AOAA. In contrast, medium lacking glucose and glutamine
      without the addition of inhibitors resulted in an increase in recovery. It is
      proposed that the efficiency of energy pathways such as glycolysis and
      glutaminolysis and their interaction are determinants of both radiosensitivity
      and recovery.

PMID- 9525261
TI  - Trans-dominant inhibition of poly(ADP-ribosyl)ation leads to decreased recovery
      from ionizing radiation-induced cell killing.
AB  - Poly(ADP-ribosyl)ation is a post-translational modification of nuclear proteins
      catalysed by poly(ADP-ribose)polymerase (PARP). PARP is strongly activated by DNA
      strand breaks and is thought to be involved in DNA repair, and various chemical
      agents that inhibit poly(ADP-ribosyl)ation have radiosensitizing properties. An
      alternative, highly specific (trans-dominant) inhibition of PARP function has
      been made possible with a molecular genetic approach where CO60 hamster cells
      were transfected with the PARP DNA-binding domain (DBD) under the control of a
      Dexamethasone (Dex)-inducible promoter. Stable transfectants were incubated with
      or without Dex and the impact of poly(ADP-ribosyl)ation on cellular radiation
      response (clonogenic survival) was measured following irradiation at high or low
      dose-rate or when potentially lethal damage (PLD) recovery was allowed. For acute
      exposures the radiosensitizing effect of PARP inhibition could be confirmed and a
      large enhancement ratio (calculated from the respective mean inactivation doses)
      of 2.2 was found for plateau phase cells. Both cellular recovery phenomena (dose
      rate sparing and PLD) were decreased in the presence of Dex, and particularly PLD
      recovery was nearly completely abolished due to the inhibition of poly(ADP
      ribosyl)ation. The latter finding strongly suggests an involvement of PARP in the
      repair of DNA double-strand breakage.

PMID- 9525262
TI  - Exposure to ionizing radiation modifies circulating gastrin levels and
      gastrointestinal endocrine cell densities in the rat.
AB  - PURPOSE: Gastrointestinal functions, controlled partly by gut peptides, are
      disturbed by ionizing radiation exposure. The effect of whole-body irradiation on
      circulating gastrin levels, densities of gastrointestinal endocrine cells and
      gastric acid secretion was investigated. MATERIALS AND METHODS: Rats were exposed
      to 2 or 6 Gy gamma-radiation. They were killed 3 or 7 days later and compared
      with shams. Plasma gastrin and basal acid output were measured. Endocrine cells
      were identified by argyrophilia or immunohistochemistry and their densities
      estimated. RESULTS: Radiation exposure significantly increased gastrinaemia and
      gastric acid output at the times studied (p<0.05-p<0.001). Endocrine cells
      displayed different sensitivities to irradiation. In the gastric mucosa, a 6 Gy
      dose induced a decrease in fundic argyrophil cell, antral gastrin and
      somatostatin cell densities, always accentuated 7 days after irradiation, while
      in the intestinal mucosa it induced an increase, with highest values often at 7
      days post-irradiation (p<0.01-p<0.001). This was true for neurotensin cells in
      the jejunum and ileum, substance P cells in ileum and enteroglucagon cells in the
      descending colon. CONCLUSIONS: Whole-body irradiation in rats significantly
      alters plasma gastrin levels, and several gut endocrine cell densities. This has
      repercussions on hormonal function, such as that exerted on acid secretion, and
      may explain gastrointestinal dysfunction observed following radiation exposure.

PMID- 9525264
TI  - Bill Cramp 1932-1997.

PMID- 9525263
TI  - Normal-tissue effects in radiotherapy: physics meets biology. Report on a
      workshop held at Hartsfield Manor, Betchworth, Surrey, UK, 14-16 July 1997.

PMID- 9525265
TI  - The menopausal experiences of women in a developing country: "there is a time for
      everything: to be a teenager, a mother and a granny".
AB  - The menopausal experiences of 26 Zimbabwean women were explored, using a
      structured open-ended interview schedule. Interviews were carried out in Harare
      in 1995. An analysis of the consensual data indicated that these women do
      experience the menopause symptoms that have been claimed elsewhere to be
      universal. Their experiences of menopause were not, however, regarded generally
      as distressing and were interpreted as a normal stage in the life cycle.
      Particular cultural beliefs are described which impact on women's understandings
      and reactions to the menopause.

PMID- 9525266
TI  - Effects of exercise participation on menstrual pain and symptoms.
AB  - Using prospective daily reporting, this study examined the relationship between
      exercise participation and menstrual pain, physical symptoms, and negative mood.
      Twenty-one sedentary women and 20 women who participated in regular exercise
      completed a modified version of the Prospective Record of the Impact and Severity
      of Menstrual Symptoms (PRISM) calendar for two complete menstrual cycles.
      Analyses revealed that pain was greater in all women during menses compared to
      the follicular and luteal phases. Moreover, exercise status was found to interact
      with menstrual cycle phase in predicting pain. Specifically, exercise
      participants reported less pain than sedentary women during menses, though there
      were no differences between the two groups during the follicular and luteal
      phases. Exercise status was also associated with greater reports of anxiety
      during menses. Otherwise, exercise status was not observed to influence reports
      of symptoms or negative mood throughout the menstrual cycle. These results
      suggest that participation in even moderate amounts of exercise affects the
      experience of menstrual pain in women.

PMID- 9525268
TI  - How gender affects psychological adjustment one year after coronary artery bypass
      graft surgery.
AB  - This research investigated gender differences in psychological adjustment among
      patients (112 males, 39 females) one year after coronary artery bypass graft
      surgery (CABG). Information regarding post-CABG depression, non-cardiac chronic
      conditions, and socioeconomic variables were obtained from a survey. Additional
      cardiac, surgical, and demographic data were retrieved from a hospital computer
      database. Women were more likely than men to experience postoperative depression,
      attributable to their poor health. Depression one year post-CABG was predicted by
      non-cardiac chronic illnesses, postoperative fatigue and shortness of breath and
      socioeconomic status.

PMID- 9525267
TI  - Wantedness of pregnancy and prenatal health behaviors.
AB  - This study examined the relationships between wantedness of pregnancy and the
      initiation of prenatal care as well as smoking and drinking alcohol during
      pregnancy. Three hundred and eighty post-partum women were interviewed in a
      randomly selected sample of Chicago area hospitals. Approximately half of the
      women said that they had wanted their recently completed pregnancy. Unadjusted
      analyses revealed that women who wanted their pregnancies were more likely to
      begin prenatal care in the first trimester and were less likely to smoke while
      there was no relationship between wantedness and alcohol use during pregnancy.
      After adjustment for sociodemographic variables, women who wanted their
      pregnancies were less likely to have smoked cigarettes or drunk alcohol during
      pregnancy, but were not more likely to have initiated prenatal care in the first
      trimester. These results suggest that positive health behaviors during pregnancy
      are influenced by wantedness of pregnancy as well as sociodemographic
      characteristics. Therefore, efforts to reduce unwanted pregnancies are an
      important strategy to improve the health of women and children.

PMID- 9525269
TI  - Gender differences in satisfaction with primary care physicians in a managed care
      health plan.
AB  - This study examines whether the formation of satisfaction with primary care
      physicians in a managed health care plan differs for men and women. Findings
      indicate that there are significant differences in the formation of satisfaction.
      For both men and women, the probability that an individual is satisfied is
      influenced by the type of plan enrolled in, number of problems experienced and
      beliefs about the quality of and access to benefits. Income and additional
      insurance coverage affects the probability of satisfaction for women only.
      Simulation analysis shows how satisfaction changes as individual characteristics
      and experience with managed care change.

PMID- 9525270
TI  - Ovarian hormone dependence of pre-malignant and malignant mammary gland lesions
      induced in pre-pubertal rats by 1-methyl-1-nitrosourea.
AB  - The experiments reported in this study were designed to examine the question of
      whether a mammary epithelial cell's independence from hormonal requirements is
      established at the time of carcinogenic initiation, or whether the emergence of
      hormone independence is associated with the process of tumor progression. A newly
      developed rat model of mammary carcinogenesis was used in which the latency
      period to lesion detection is very short and in which the frequencies of both pre
      malignant and malignant mammary lesions can be quantified. Two experiments were
      conducted in Sprague-Dawley rats injected with 50 mg MNU/kg body wt at 21 days of
      age. In the first experiment 47 animals were ovariectomized after the detection
      of a mammary tumor of palpable size. Forty-six of the 47 tumors assessed, all of
      which were subsequently classified as mammary gland adenocarcinomas, regressed to
      <50% of their initial volume within 14 days of bilateral ovariectomy. However,
      both pre-malignant and malignant mammary gland lesions were observed when animals
      were killed. In Experiment 2 a total of 60 rats were ovariectomized 7 days after
      MNU was injected. At 35 days post carcinogen ovariectomized animals had a higher
      incidence of intraductal proliferations than sham-operated controls (P = 0.03);
      there was no effect of ovariectomy on the incidence of ductal carcinoma in situ
      or carcinoma. The multiplicity of intraductal proliferations was increased by 58%
      in ovariectomized rats (P = 0.12), but the number of mammary carcinoma per rat
      was reduced (3.8 vs. 1.57, P = 0.02). These data are consistent with the
      hypotheses that the progression of pre-malignant to malignant lesions is
      inhibited in the mammary gland by ovariectomy and that the hormone independent
      phenotype can be conferred at the time of carcinogenic initiation.

PMID- 9525271
TI  - Human microsomal epoxide hydrolase: 5'-flanking region genetic polymorphisms.
AB  - Microsomal epoxide hydrolase (mEH) catalyses the hydrolysis of xenobiotic
      epoxides, including various epoxide derivatives of the procarcinogenic
      polyaromatic hydrocarbons. Levels of mEH enzymatic activity among different cell
      types and between individuals within the population vary considerably. Genetic
      polymorphisms within the structural region of the human mEH gene exist and appear
      to contribute to the population variance in functional expression. In this study,
      we used single strand conformational polymorphism analysis and direct DNA
      sequencing approaches to identify seven additional polymorphic sites within the
      upstream region of the mEH gene, spanning -743 to +185 bp, relative to the
      transcription initiation site. Allelic frequencies and linkages of the
      polymorphic nucleotides were determined in 51 individuals using restriction
      fragment length polymorphism or competitive oligonucleotide priming assays. To
      determine the functional significance of the individual nucleotide substitutions,
      DNA fragments representing the variant alleles were cloned into the heterologous
      pBRAMScat2 reporter vector, transfected into HepG2 cells and assessed for
      reporter gene expression. Results indicated that certain of these polymorphic
      loci might differentially regulate transcription, with the maximum contribution
      of any of the variants modifying levels of reporter gene activity by
      approximately 30%. These observations establish that genetic variation in the 5'
      flanking sequence of mEH gene is likely an additional contributing factor to the
      range of functional mEH expression existing in human populations.

PMID- 9525272
TI  - Induction and localization of cytochrome P450 1B1 (CYP1B1) protein in the livers
      of TCDD-treated rats: detection using polyclonal antibodies raised to histidine
      tagged fusion proteins produced and purified from bacteria.
AB  - Knowledge of the response of cytochrome P450 1B1 (CYP1B1) to exposure to 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD) in both humans and rodents is limited. To
      improve the analysis of CYP1 proteins, specific CYP1B1 and CYP1A1 polypeptides
      were expressed as hexahistidine-tagged fusion proteins in Escherichia coli,
      purified to homogeneity and used to produce polyclonal antibodies in rabbits.
      Immunoblot analyses showed that these antibodies were specific and sensitive,
      detecting both the human and rat forms of the respective isozymes and exhibiting
      negligible cross-reactivity between the two known CYP1 subfamilies. We show that
      CYP1B1, CYP1A1 and CYP1A2 protein levels were induced in the livers of female
      Sprague-Dawley rats following either acute (single dose of 25 microg TCDD/kg) or
      chronic (125 ng TCDD/kg/day for 30 weeks) exposure to TCDD. CYP1B1 protein
      exhibited a dose-response to TCDD that was different from those of CYP1A1 and
      CYP1A2. CYP1B1 induction appeared to be less sensitive to TCDD exposure, with
      induction occurring at higher doses of TCDD than that required for induction of
      CYP1A1 or CYP1A2. Immunohistochemical analysis showed that in animals chronically
      exposed to TCDD (35 ng/kg/day for 30 weeks), CYP1B1 was induced only in
      centrilobular hepatocytes, a pattern of expression similar to that of CYP1A1 and
      CYP1A2. These observations of cellular co-localization of the CYP1 cytochromes in
      livers of TCDD-treated rats and apparent differences in both protein amounts and
      dose-response are indicative of both common and unique regulation of CYP1
      induction.

PMID- 9525274
TI  - Elevated DNA single-strand breakage frequencies in lymphocytes of welders exposed
      to chromium and nickel.
AB  - DNA damage (alkaline filter elution) and sister chromatid exchange (SCE)
      frequencies were measured in lymphocytes of 39 welders and 39 controls. The
      welders showed a significantly higher rate of DNA single-strand breakages and
      significantly elevated SCE values. These results are not in accordance with those
      of a former study in which only DNA-protein cross-links were measured. The
      different results may be explained on the basis of different exposure levels for
      chromium(VI) and nickel. Both methods are not specific but sensitive enough to
      measure genotoxic damage after occupational exposure to chromium(VI) and nickel
      in the range of threshold values for the workplace on a collective basis.
      Additionally, the results indicate that DNA single-strand breakage and DNA
      protein cross-links show different increases depending on the exposure levels for
      chromium and nickel.

PMID- 9525273
TI  - Dietary carotenoids inhibit aflatoxin B1-induced liver preneoplastic foci and DNA
      damage in the rat: role of the modulation of aflatoxin B1 metabolism.
AB  - To study the effects of carotenoids on the initiation of liver carcinogenesis by
      aflatoxin B1 (AFB1), male weanling rats were fed beta-carotene, beta-apo-8'
      carotenal, canthaxanthin, astaxanthin or lycopene (300 mg/kg diet), or an excess
      of vitamin A (21000 RE/kg diet), or were injected i.p. with 3-methylcholanthrene
      (3-MC) (6 x 20 mg/kg body wt) before and during i.p. treatment with AFB1 (2 x 1
      mg/kg body wt). The rats were later submitted to 2-acetylaminofluorene treatment
      and partial hepatectomy, and placental glutathione S-transferase-positive liver
      foci were detected and quantified. The in vivo effects of carotenoids or of 3-MC
      on AFB1-induced liver DNA damage were evaluated using different endpoints: liver
      DNA single-strand breaks (SSB) induced by AFB1, and in vivo binding of [3H]AFB1
      to liver DNA and plasma albumin. Finally, the modulation of AFB1 metabolism by
      carotenoids or by 3-MC was investigated in vitro by incubating [14C]AFB1 with
      liver microsomes from rats that had been fed with carotenoids or treated by 3-MC,
      and the metabolites formed by HPLC were analyzed. In contrast to lycopene or to
      an excess of vitamin A, both of which had no effect, beta-carotene, beta-apo
      8'carotenal, astaxanthin and canthaxanthin, as well as 3-MC, were very efficient
      in reducing the number and the size of liver preneoplastic foci. In a similar way
      as 3-MC, the P4501A-inducer carotenoids, beta-apo-8'-carotenal astaxanthin and
      canthaxanthin, decreased in vivo AFB1-induced DNA SSB and the binding of AFB1 to
      liver DNA and plasma albumin, and increased in vitro AFB1 metabolism to aflatoxin
      M1, a less genotoxic metabolite. It is concluded that these carotenoids exert
      their protective effect through the deviation of AFB1 metabolism towards
      detoxication pathways. In contrast, beta-carotene did not protect hepatic DNA
      from AFB1-induced alterations, and caused only minor changes of AFB1 metabolism:
      seemingly, its protective effect against the initiation of liver preneoplastic
      foci by AFB1 is mediated by other mechanisms.

PMID- 9525275
TI  - Quantitation of chemopreventive synergism between (-)-epigallocatechin-3-gallate
      and curcumin in normal, premalignant and malignant human oral epithelial cells.
AB  - An in vitro model for oral cancer was used to examine the growth inhibitory
      effects of chemopreventive agents when used singly and in combination. The model
      consists of primary cultures of normal oral epithelial cells, newly established
      cell lines derived from dysplastic leukoplakia and squamous cell carcinoma. Two
      naturally occurring substances, (-)-epigallocatechin-3-gallate (EGCG) from green
      tea and curcumin from the spice turmeric were tested. Cells were treated singly
      and in combination and effects on growth determined in 5-day growth assays and by
      cell cycle analysis. Effective dose 50s and the combination index were calculated
      with the computerized Chou-Talalay method which is based on the median-effect
      principle. Agents were shown to differ in their inhibitory potency. EGCG was less
      effective with cell progression; the cancer cells were more resistant than normal
      or dysplastic cells. In contrast, curcumin was equally effective regardless of
      the cell type tested. Cell cycle analysis indicated that EGCG blocked cells in
      G1, whereas curcumin blocked cells in S/G2M. The combination of both agents
      showed synergistic interactions in growth inhibition and increased sigmoidicity
      (steepness) of the dose-effect curves, a response that was dose and cell type
      dependent. Combinations allowed for a dose reduction of 4.4-8.5-fold for EGCG and
      2.2-2.8-fold for curcumin at ED50s as indicated by the dose reduction index
      (DRI). Even greater DRI values were observed above ED50 levels. Our results
      demonstrate that this model which includes normal, premalignant and malignant
      oral cells can be used to analyse the relative potential of various
      chemopreventive agents. Two such naturally-occurring agents, EGCG and curcumin,
      were noted to inhibit growth by different mechanisms, a factor which may account
      for their demonstrable interactive synergistic effect.

PMID- 9525276
TI  - Chemoprevention of 4-nitroquinoline 1-oxide-induced oral carcinogenesis by citrus
      auraptene in rats.
AB  - The modifying effects of citrus auraptene given during the initiation and post
      initiation phases of oral carcinogenesis initiated with 4-nitroquinoline 1-oxide
      (4-NQO) were investigated in male F344 rats. At 6 weeks of age, animals were
      divided into experimental and control groups, and fed the diets containing 100
      ppm or 500 ppm auraptene. At 7 weeks of age, all animals except those treated
      with auraptene alone and control groups were given 4-NQO (20 ppm) in the drinking
      water for 8 weeks to induce tongue carcinoma. Starting 7 days before the 4-NQO
      exposure, groups of animals were fed the diets containing auraptene (100 and 500
      ppm) for 10 weeks and then switched to the basal diet. Starting 1 week after the
      cessation of 4-NQO exposure, the groups given 4-NQO and a basal diet were
      switched to the diets mixed with auraptene (100 and 500 ppm), and maintained on
      these diets for 22 weeks. The other groups consisted of rats fed auraptene alone
      (500 ppm) or untreated rats. All rats were necropsied at the termination of the
      study (week 32). The incidences of tongue lesions (neoplasms and preneoplasms),
      polyamine levels in the tongue tissue and cell proliferation activity estimated
      by 5-bromodeoxyuridine (BrdU)-labelling index were compared among the groups. In
      addition, the activities of gluthathione S-transferase (GST) and quinone
      reductase (QR) in liver and tongue of rats gavaged various doses of auraptene (0,
      200, 400 and 800 mg/kg body wt) for 5 days were assayed. Feeding of auraptene at
      both doses during the initiation phase caused a significant reduction in the
      frequency of tongue carcinoma (100 ppm auraptene, 91% reduction, P < 0.001; 500
      ppm auraptene, 63% reduction, P < 0.05). When fed auraptene after 4-NQO exposure,
      the frequency of tongue carcinoma was also decreased (100 ppm auraptene, 100%
      reduction, P < 0.001; 500 ppm auraptene, 74% reduction, P < 0.01). The incidences
      of tongue severe dysplasia in these groups were significantly smaller than those
      in carcinogen controls (P < 0.05). There were no pathological alterations in rats
      treated with 500 ppm auraptene alone or those in an untreated control group.
      Dietary administration of auraptene significantly decreased BrdU-labelling index
      and polyamine concentrations in the oral mucosa (P < 0.05). In addition,
      auraptene administration significantly increased the activities of GST and QR in
      the liver and tongue. Although dose-dependent effect was not found, citrus
      auraptene is effective in inhibiting the development of oral neoplasms induced by
      4-NQO. Thus, suppression by the initiation-feeding of auraptene might relate to
      elevation in the phase II enzymes GST and QR of the liver and tongue, and
      inhibition occurring during the post-initiation might be related to suppression
      of increased cell proliferation caused by 4-NQO in the oral mucosa.

PMID- 9525277
TI  - Differences in the catalytic efficiencies of allelic variants of glutathione
      transferase P1-1 towards carcinogenic diol epoxides of polycyclic aromatic
      hydrocarbons.
AB  - Previous studies have identified allelic variants of the human glutathione
      transferase (GST) Pi gene and showed that the two different encoded proteins with
      isoleucine (GSTP1-1/I-105) or valine (GSTP1-1/V-105) at position 105,
      respectively, differ significantly in their catalytic activities with model
      substrates. Moreover, recent epidemiological studies have demonstrated that
      individuals differing in the expression of these allelic variants also differ in
      susceptibility to tumour formation in certain organs, including such in which
      polycyclic aromatic hydrocarbons (PAH) may be etiological factors. In the present
      study the catalytic efficiencies (kcat/Km) of these GSTP1-1 variants were
      determined with a number of stereoisomeric bay-region diol epoxides, known as the
      ultimate mutagenic and carcinogenic metabolites of PAH, including those from
      chrysene, benzo[a]pyrene and dibenz[a,h]anthracene. In addition, GSTP1-1 mutants
      in which amino residue 105 is alanine (GSTP1-1/A-105) or tryptophan (GSTP1-1/W
      105) have been constructed and characterized. GSTP1-1/V-105 was found to be more
      active than GSTP1-1/I-105 in conjugation reactions with the bulky diol epoxides
      of PAH, being up to 3-fold as active towards the anti- and syn-diol epoxide
      enantiomers with R-absolute configuration at the benzylic oxiranyl carbon.
      Comparing the four enzyme variants, GSTP1-1/A-105 generally demonstrated the
      highest kcat/Km value and GSTP1-1/W-105 the lowest with the anti-diol epoxides. A
      close correlation was observed between the volume occupied by the amino acid
      residue at position 105 and the value of kcat/Km. With the syn-diol epoxides,
      such a correlation was observed with alanine, valine and isoleucine, whereas
      tryptophan was associated with increased kcat/Km values. The mutational
      replacement of isoleucine with alanine or tryptophan at position 105 did not
      alter the enantio selectivity of the GSTP1-1 variants compared with the naturally
      occurring allelic variants GSTP1-1/I-105 and GSTP1-1/V-105. Since the amino acid
      at position 105 forms part of the substrate binding site (H-site) the effect of
      increasing bulkiness is expected to cause restricted access of the diol epoxide
      and proper alignment of the two reactants for efficient glutathionylation. In
      conclusion, the present study indicates that individuals who are homozygous for
      the allele GSTP1* B (coding for GSTP1-1/V-105) display a higher susceptibility to
      malignancy because of other factors than a decreased catalytic efficiency of
      GSTP1-1/V-105 in the detoxication of carcinogenic diol epoxides of benzo[a]pyrene
      or structurally related PAH.

PMID- 9525278
TI  - Oxidation of eugenol to form DNA adducts and 8-hydroxy-2'-deoxyguanosine: role of
      quinone methide derivative in DNA adduct formation.
AB  - We have investigated the activation of eugenol to form DNA adducts and oxidative
      base damage. Treatment of myeloperoxidase containing HL-60 cells with eugenol,
      produced a dose-dependent formation of three DNA adducts as detected with P1
      enhanced 32P-post-labeling. Incubation of HL-60 cells with the combination of 100
      microM eugenol and 100 microM H2O2 potentiated the levels of DNA adduct in HL-60
      cells by 14-fold, which suggests peroxidase activation in adduct formation. In
      vitro activation of eugenol with either horseradish peroxidase or myeloperoxidase
      and H2O2 produced three DNA adducts that were inhibited by the addition of either
      ascorbic acid or glutathione, by 66 and 90%, respectively. The DNA adducts formed
      in HL-60 cells treated with eugenol were the same as those formed by in vitro
      peroxidase activation. In addition to adduct formation, peroxidase activation of
      eugenol produced a 2- to 3-fold increase in the level of oxidative base damage.
      Eugenol quinone methide was prepared by Ag(I)oxide oxidation of eugenol.
      Peroxidase activation of eugenol gave a product that had the same UV spectrum as
      eugenol quinone methide, which suggests that it was one of the products. Reaction
      of eugenol quinone methide with either DNA or deoxyguanosine-3'-phosphate
      produced two principal adducts (2 and 4). When DNA adduct 2 formed by incubation
      of eugenol quinone methide with deoxyguanosine-3'-phosphate was compared with DNA
      2 adduct formed in HL-60 cells treated with eugenol results demonstrated that
      they were the same. This suggests that eugenol quinone methide is one of the
      reactive intermediates leading to DNA adduct formation in cells. Activation of
      eugenol with 10 microM copper sulfate resulted in the production of one principal
      (2) and several minor adducts. DNA adduct 2 formed by activation of eugenol with
      copper sulfate was the same as DNA adduct 2 formed by either peroxidase
      activation of eugenol or by reactions with eugenol quinone methide, which
      indicates that the reactive intermediates generated by these activation systems
      were similar. Copper sulfate produced a 95-fold increase in the level of
      oxidative base damage, which was significantly inhibited by the addition of
      either bathocuproinedisulphonic acid or catalase. The formation of oxidative base
      damage was consistent with a Fenton reaction mechanism. Our results demonstrate
      that eugenol can be activated to form both DNA adducts and oxidative base damage.
      We propose that the formation of this DNA damage may contribute to the observed
      toxic properties of eugenol.

PMID- 9525279
TI  - Beta2 integrin/ICAM-1 adhesion molecule interactions in cutaneous inflammation
      and tumor promotion.
AB  - The beta2 integrin (CD 18/CD 11 a, b, c) family of proteins mediate adherence of
      leukocytes to vascular endothelium and the associated ligand, intercellular
      adhesion molecule-1 (ICAM-1; CD 54), interacts with beta2 integrin proteins to
      allow transendothelial migration of leukocytes into sites of inflammation. The
      present study examines the function of these proteins in a murine model of acute
      cutaneous inflammation induced following topical application of 12-O
      tetradecanoylphorbol-13-acetate (TPA) to the dorsal epidermis of SENCAR mice and
      in a model of skin multistage carcinogenesis. At 24 h following topical
      application of TPA to the dorsal epidermis of mice, dermal leukocytes expressed
      higher levels of beta2 integrin protein compared with the lower levels of beta2
      integrin protein expression by peripheral blood leukocytes. ICAM-1 protein was
      localized to epidermal keratinocytes and vascular endothelium in TPA-treated skin
      and to proliferating papilloma cells. Intravenous (i.v.) injection of either 50
      microg anti-beta2 integrin antibody alone or in combination with anti-ICAM-1
      antibody significantly inhibited both TPA-stimulated neutrophil infiltration into
      the dermis (P < 0.001) and myeloperoxidase (MPO) activity (P < 0.03 anti-beta2
      integrin antibody; P < 0.01 anti-beta2 integrin + ICAM-1 adhesion molecule
      antibodies), but had no effect on TPA-induced epidermal hyperplasia. In addition,
      injection of either anti-ICAM-1 adhesion molecule antibody alone (P < 0.004) or
      in combination with anti-beta2 integrin antibody (P < 0.001) significantly
      inhibited TPA-induced production of 7,8-dihydroxy-2'-deoxyguanosine (8-OHdG)
      immunoreactive proteins by epidermal keratinocytes. Beta2 integrin/ICAM-1
      adhesion molecules work in concert to regulate migration, retention and
      functional activation of leukocytes within the dermis during TPA-induced skin
      inflammation and within stromal tissue of papillomas that form during multi-stage
      carcinogenesis. Agents that inhibit these receptor/ligand interactions may be
      useful in defining the roles of specific cell populations in cutaneous
      inflammation and multistage carcinogenesis and may also have potential as anti
      promoting and anti-progression agents.

PMID- 9525280
TI  - Comparison of mutagenesis by O6-methyl- and O6-ethylguanine and O4-methylthymine
      in Escherichia coli using double-stranded and gapped plasmids.
AB  - To compare mutagenesis by O6-methylguanine (m6G), O4-methylthymine (m4T) and O6
      ethylguanine (e6G), and assess their genotoxicity in Escherichia coli, double
      stranded and gapped plasmids were constructed containing a single m6G, e6G or m4T
      in the initiation codon (ATG) of a lacZ' gene. Modified base induced mutations
      were scored by the loss of lacZ' activity on X-gal-containing media resulting in
      formation of white or sectored (mutant) rather than blue (non-mutant) colonies.
      Genotoxicity experiments with gapped plasmids containing the modified bases
      indicated that m4T produced a greater number of bacterial colonies than m6G or
      e6G. m4T was more mutagenic (45% mutant colonies) than m6G (6%) or e6G (11%) in
      repair competent (w.t.) E. coli when incorporated in double-stranded plasmids. In
      gapped plasmids, m4T produced 99% mutant colonies (as was observed previously for
      e6G) in both w.t. E. coli or E. coli deficient in both O6-alkylguanine-DNA
      alkyltransferases as well as methylation-directed mismatch repair (ada(-)-ogt(-)
      mutS[-]). m6G in gapped plasmids produced 62% mutant colonies in w.t. E. coli,
      but this percentage increased to 94% in the ada(-)-ogt(-)-mutS(-) strain. In
      double-stranded plasmids both m4T and m6G produced very similar distributions of
      mutant and non-mutant colonies in the ada(-)-ogt(-)-mutS(-) strain. These
      observations led to the conclusion that differences in the mutagenicity of m6G
      and m4T in w.t. E. coli were a result of preferential repair of m6G compared to
      m4T by alkyltransferase and mismatch repair mechanisms, and did not reflect
      differences in their respective coding efficiency or their inherent
      obstructiveness to DNA synthesis as was observed with e6G. The combination of
      alkyltransferase and mismatch repair was concluded to be primarily responsible
      for the apparent genotoxicity of m6G compared to m4T in double-stranded plasmids.

PMID- 9525281
TI  - Levels and membrane localization of the c-K-ras p21 protein in lungs of mice of
      different genetic strains and effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin
      (TCDD) and Aroclor 1254.
AB  - Mutational activation of the K-ras oncogene often occurs in human and mouse lung
      adenocarcinomas. Since K-ras p21 functions in trans-membrane signaling, we have
      investigated whether the amount of this protein in lung cell membranes is a
      variable that could influence lung tumorigenesis, either due to genetic
      differences or in response to tumor promoters. The six mouse strains assessed
      showed little difference in the total lung K-ras p21 after immunoprecipitation
      and immunoblotting. However, amount of ras p21 in the membrane fraction showed
      significant differences, with C57BL/6 and BALB/c having 3-5-fold more than NIH
      Swiss, AKR and DBA mice. Interestingly, a congenic AKR strain having the Ahr(b-1)
      Ah receptor allele from C57BL/6 mice (designated AKR.B6Ah) had high lung membrane
      K-ras p21 similar to that of C57BL/6. To test for possible changes related to
      lung tumor promotion, mice were treated with a promotional dose of TCDD (5
      nmol/kg). After 48 h C57BL/6 lungs showed an increase in p21 in both total and
      membrane fractions. BALB/c, DBA and Swiss mice showed an increase only in
      membranes. There was no change in the AKR and AKR.B6Ah. Aroclor 1254 (250 mg/kg)
      caused an increase in membrane/cytosol ratio in Swiss mice. Thus the
      membrane:cytosol K-ras p21 ratio may be influenced by the Ahr phenotype, and TCDD
      and PCBs can induce p21 or increase its membrane level in certain strains, but
      these properties are not fully dependent on Ahr receptor type. In confirmation of
      the relevance of these findings for the tumor target cell type, the immortalized
      alveolar type 2 E10 cell line presented K-ras p21 in membrane, and this was
      increased 4-fold by treatment with 10 nM TCDD.

PMID- 9525282
TI  - Prevention of estrogen carcinogenesis in the hamster kidney by ethinylestradiol:
      some unique properties of a synthetic estrogen.
AB  - Ethinylestradiol (EE) has evident paradoxical effects on cancer risk for human
      breast and hepatic cancer which parallel in some respects its effects on estrogen
      induced neoplasms in the hamster kidney and liver. EE has been shown to be only
      weakly carcinogenic in the hamster kidney, but the most potent carcinogenic
      estrogen in the hamster liver following prolonged treatment. Unexpectedly, when
      EE and potent carcinogenic estrogens, such as diethylstilbestrol (DES), 17beta
      estradiol (E2) and Moxestrol (MOX), are administered concomitantly, estrogen
      induced carcinogenesis in the kidney is completely prevented. In studying this
      novel finding, we found that, compared with E2 exposure alone, EE at 0.05 and 1.0
      nM significantly (P < 0.001) inhibited the rise in proliferation of cultured
      primary hamster proximal renal tubular (PRT) cells in the presence of E2 (1.0
      nM). Consistent with these findings, combined EE + DES treatment for 5.0 months
      reduced hamster kidney c-myc, c-fos and c-jun RNA expression to 43, 37 and 52%,
      respectively, compared with levels observed after DES treatment alone.
      Interestingly, TAM + DES treatment for the same period also resulted in the same
      low level of RNA expression of these proto-oncogenes. c-MYC, c-FOS and c-JUN
      protein products were comparably reduced after either EE + DES or TAM + DES
      treatment. It appears that c-fos expression and c-FOS protein levels in the
      hamster kidney were more responsive to TAM inhibition. These data demonstrate
      that EE possesses unique anti-tumorigenic properties in vivo in the hamster
      kidney. Additionally, the observed anti-estrogen-like effect of EE on cell
      proliferation of cultured PRT cells suggests that EE may interfere critically
      with estrogen receptor (ER)-mediated mitogenic pathway(s) affected by potent
      carcinogenic estrogens, thus preventing subsequent gene dysregulation and, hence,
      tumor development. Based on competition studies, the differential binding of EE
      to hamster kidney ER relative to that of the other estrogens (E2, DES, MOX)
      appears not to contribute to the prevention of estrogen carcinogenesis at this
      organ site by EE.

PMID- 9525283
TI  - Modulation of human epidermal cell response to 2,3,7,8-tetrachlorodibenzo-p
      dioxin by epidermal growth factor.
AB  - Cultured human epidermal cells were treated with 2,3,7,8-tetrachlorodibenzo-p
      dioxin (TCDD) in the presence or absence of epidermal growth factor (EGF). In
      both normal keratinocytes and a spontaneously immortalized keratinocyte (SIK)
      line, TCDD treatment in the absence of EGF induced a marked reduction in colony
      size and cell number, and it perturbed colony morphology. These effects were
      largely prevented by EGF, indicating that growth factor action in the cellular
      microenvironment may considerably modify TCDD action in target cells. Both TCDD
      and EGF substantially reduced expression of the differentiation markers keratin 1
      and keratin 10 in the normal and immortalized cells, and did so in an additive
      fashion. The cells did not display a general loss of differentiated function,
      since several other markers, including involucrin, were little affected. EGF
      dramatically stimulated telomerase activity in SIK cultures, and TCDD prevented
      this action but not by reducing cell growth. However, EGF did not stimulate
      telomerase activity in normal human epidermal cells despite an evident increase
      in their growth. The growth factor stimulation of telomerase in the minimally
      deviated SIK line suggests that derepression of enzyme activity in normal cells
      may occur in a stepwise fashion during neoplastic progression. TCDD could act as
      a late stage tumor promoter by selecting for variants in which telomerase is
      constitutively active.

PMID- 9525285
TI  - Local metabolism in lung airways increases the uncertainty of pyrene as a
      biomarker of polycyclic aromatic hydrocarbon exposure.
AB  - While inhaled polycyclic aromatic hydrocarbons have long been suspected to induce
      lung cancer in humans, their dosimetry has not been fully elucidated. A key
      question is whether the critical exposure occurs during absorption in the lungs,
      or if toxicants in the systemic circulation contribute significantly to lung
      cancer risk. In particular, data are needed to determine how the physical
      properties of inhalants affect local dosimetry in the respiratory tract. Pyrene,
      a tobacco smoke component, was selected for study because it has physical
      properties between those of highly lipophilic benzo[a]pyrene and water-soluble
      nitrosamines. Aliquots of 5 ng of pyrene dissolved in a phospholipid/ saline
      suspension were instilled as a single-spray bolus in the posterior trachea of the
      dog just anterior to the carina. For 3 h after instillation, blood was repeatedly
      sampled from the azygous vein, which drains the mucosa around the point of
      instillation, and from both sides of the systemic circulation. At 3 h post
      instillation, tissue samples were taken. Autoradiography was used to determine
      the depth distribution of pyrene in the tracheal mucosa. The concentration of
      pyrene-equivalent radioactivity in the azygous vein peaked 9 min after the
      instillation. At approximately 30 min after instillation, a rapid early clearance
      phase shifted into a distinctly slower second clearance phase. Rates of rapid
      clearance were, however, sufficiently slow to indicate diffusion-limited
      absorption of pyrene in the trachea. This finding was corroborated by high
      concentrations of pyrene in the epithelium as determined by autoradiography. High
      epithelial concentration of pyrene combined with a slow penetration into the
      circulating blood allowed substantial first-pass metabolic conversion of pyrene
      in the tracheal mucosa. A total of 13% of the instilled pyrene was retained in
      the tracheal mucosa 3.2 h after instillation; of this, 29% was parent compound,
      52% was organic-extractable metabolites, 14% was water-soluble metabolites and 6%
      (approximately 1% of the instilled amount) was covalently bound to tracheal
      tissues. Results support the inference that lipophilic protoxicants, because of
      slow, diffusion-limited absorption, are more likely than water-soluble
      protoxicants to be bioactivated in the lining epithelium and, in turn, induce
      first-pass toxicity at the site of entry. In addition, limitations were
      identified in the use of systemically distributed biomarkers of PAHs, such as
      urinary hydroxypyrene levels, as indicators of the biologically effective dose in
      airway target cells.

PMID- 9525284
TI  - Relationships between the synthesis of N-nitrosodimethylamine and immune
      responses to chronic infection with the carcinogenic parasite, Opisthorchis
      viverrini, in men.
AB  - This study investigated the relationship between immune responses to infection
      with the liver fluke, Opisthorchis viverrini, and the synthesis of the
      carcinogen, N-nitrosodimethylamine (NDMA) in humans. It also examined
      associations between synthesis of nitric oxide (NO) and nitrosation of amines, in
      vivo. Antibody and T cell responses to fluke antigens and post-alcohol urinary
      NDMA excretion were assessed among three groups of 40-50 men with no, moderate
      and heavy liver fluke infection. Markers of NO synthesis (nitrate, nitrite) and
      nitrosation (nitrosamino acids) were also measured in biological fluids.
      Assessments were carried out under controlled conditions which minimised intake
      of exogenous nitrate and nitrite and were carried out at two time points, namely
      before and 4 months after elimination of the infection with praziquantel
      treatment. No statistically significant variation was observed in the amount of
      NDMA excreted between the 3 groups. However, during active infection, a strong
      negative association was observed between in vitro lymphoproliferative responses
      to some liver fluke antigens and NDMA excretion. After treatment this association
      was reduced. Multivariate statistical models revealed a highly significant
      relationship between NDMA levels and urinary nitrate, stimulation indices for two
      T cell responses to two parasite antigens (MW 37 kDa and 110 kDa) and gall
      bladder dimensions. NDMA levels after treatment were best described by the ratio
      between parasite-specific IgG2 and IgE, background levels of T cell
      proliferation, a urinary marker of nitrosation (N-nitrosothioproline) and usual
      level of alcohol consumption. These results suggest that individual background
      immunologic activity, parasite-specific responses and/or parasite products and NO
      synthesis are important determinants of endogenous generation of nitrosamines in
      O. viverrini-infected humans.

PMID- 9525286
TI  - Inhibition of spontaneous formation of lung tumors and rhabdomyosarcomas in A/J
      mice by black and green tea.
AB  - We investigated the effects of black tea (BT) and green tea (GT) infusion on the
      spontaneous formation of lung tumors and rhabdomyosarcomas in A/J mice. Female
      A/J mice, 6 weeks of age, were allocated into five groups (50 per group) and were
      given the following as the sole source of drinking fluid: (i) deionized water
      (control group), (ii) 0.5% BT, (iii) 1% BT, (iv) 2% BT and (v) 1% GT. After 60
      weeks, the mice were killed by decapitation. Lung tumor incidence, multiplicity
      and volume were significantly lower in the 2% BT group as compared with the
      controls (27 versus 52%, 0.33 versus 0.72 tumors/mouse and 4.27 versus 38.3 mm3,
      respectively). The 1% GT group had significantly lower lung tumor multiplicity
      (0.41/mouse), while the 1% BT group had significantly decreased tumor volume
      (7.17 mm3). Rhabdomyosarcomas were found in 34% of the mice in the control group,
      and both the 1 and 2% BT groups had significantly lower incidences at 13 and 14%,
      respectively. The mice in the 2% BT group weighed 16% less than those in the
      control group, although they consumed more food than the control group. The other
      tea-consuming groups also weighed less than the control group (7.8-11%) while
      consuming more food and fluid. In a separate experiment, similar carcinogenesis
      inhibition was also observed in female A/J mice that were given 0.6% and then
      0.3% instant black tea for 52 weeks. These results demonstrate the inhibitory
      activity of BT against the spontaneous formation of lung tumors and
      rhabdomyosarcomas in mice.

PMID- 9525287
TI  - p53, but not p16 mutations in oral squamous cell carcinomas are associated with
      specific CYP1A1 and GSTM1 polymorphic genotypes and patient tobacco use.
AB  - Inactivation of tumor suppressor genes like p53 and p16 play a key role in tumor
      progression, with a high incidence of mutations existing for both genes in oral
      squamous cell carcinomas. Previous studies have demonstrated, (i) a correlation
      between the prevalence of p53 mutations and tobacco use [Brennan et al. (1995)
      New Engl. J. Med., 332, 712-717; Lazarus et al. (1996) Carcinogenesis, 17, 733
      739], and (ii) a link between genotypes in specific xenobiotic metabolizing
      enzymes and oral cancer susceptibility [Park et al. (1997) Cancer Epid.
      Biomarkers Prev., 6, 791-797). In this paper, we present results of our
      examination of a series of 80 oral squamous cell carcinomas for p53 exons 5-9 and
      p16 exons 1-2 mutations, and the potential association of these mutations with
      specific genotyping patterns. p53 mutation prevalence in oral tumors was linked
      with increased patient tobacco use using several stratification criteria. There
      was a significantly higher prevalence of p53 mutations in OCSCCs from patients
      who smoked > 30 pack-years as compared to tumors from patients who smoked < or =
      30 pack-years (OR = 2.8; CI = 1.1-7.2). No significant association was observed
      with patient alcohol consumption. There was a significant association between the
      prevalence of p53 mutations in oral tumors and CYP1A1 genotyping patterns in
      these oral cancer patients, with the highest p53 mutation prevalence observed in
      subjects with the CYP1A1 [val]/GSTM1 [+] genotype (OR = 6.0; CI = 1.2-29.7). A
      significant association was not observed between the prevalence of p16 mutations
      in oral tumors and tobacco use, or CYP1A1 [val] or GSTM1 (0/0) genotypes. These
      data suggest that the induction of mutations in specific tumor suppressor genes
      or oncogenes in oral tumors may be associated with specific carcinogen exposures,
      and that this association may be linked to specific polymorphic genotypes in
      xenobiotic-metabolizing enzyme genes.

PMID- 9525288
TI  - Molecular dosimetry of DNA adducts in the medaka small fish model.
AB  - Small fish models are being used with increasing frequency for carcinogenicity
      testing and comparative cancer research in the US, Canada and Europe. However,
      there is a need to further define the early biochemical events of carcinogenesis
      in these species. Identification and quantitation of DNA adducts can integrate
      all of the various factors involved in chemical exposure, uptake, distribution
      and biotransformation of a putative carcinogen. In the present study, Japanese
      medaka (Oryzias latipes) were exposed to the alkylating agent, diethylnitrosamine
      (DEN), in the ambient water. Liver DNA was analyzed for O6-ethylguanine (O6EG),
      O4-ethylthymidine (O4ET) and O2-ethylthymidine (O2ET) by the immuno-slot-blot
      technique, using monoclonal antibodies against each adduct of interest. While
      fish exposed to 10 p.p.m. DEN had liver DNA adduct concentrations at or only
      slightly higher than background levels, those exposed to 100 p.p.m. DEN averaged
      34 and 53 pmol O6EG/micromol guanine, 15 and 41 pmol O2ET/micromol thymidine and
      2 and 6 pmol O4ET/micromol thymidine at 0 and 24 h post-exposure, respectively.
      The results of this study show that, under these short-term exposure conditions,
      ethyl-DNA adducts appear to accumulate in medaka liver tissue in a sublinear
      (i.e. non-linear) fashion after aqueous exposure to DEN. Thus, critical DNA
      repair enzymes such as O6-alkylguanine DNA alkyltransferase, which are relatively
      efficient at lower carcinogen levels, are probably saturated at the 100 p.p.m.
      concentration level of DEN.

PMID- 9525289
TI  - Adaptive response of human melanoma cells to methylglyoxal injury.
AB  - The effects of methylglyoxal on the growth of a line of human melanoma cells are
      investigated. Methylglyoxal inhibits cell growth in a dose-dependent manner and
      causes an increase in glyceraldehyde 3-phosphate dehydrogenase, and glyoxalase 1
      and glyoxalase 2 specific activities. The cellular response to increasing
      concentrations of methylglyoxal in the culture medium is also studied by
      measuring L-lactate production, reduced-oxidized glutathione levels and apoptotic
      cell death. Methylglyoxal seems to promote a change of cell population phenotypic
      repertoire toward a more monomorphic phenotype. In conclusion, methylglyoxal
      seems to induce an enzymatic cellular response that lowers methylglyoxal levels
      and selects the most resistant cells.

PMID- 9525290
TI  - Deletion analysis of human AP-endonuclease: minimum sequence required for the
      endonuclease activity.
AB  - AP-endonuclease (APE) plays a central role in the base excision repair process
      for oxidative and alkylation damage in DNA. The major human APE with 318 amino
      acid residues possesses transcriptional regulatory activities for which the N
      terminal region was found to be essential. Systematic deletion studies of both
      amino and carboxyl termini of the human APE have shown that the carboxyl termini
      residues are essential for the endonuclease activity as indicated by direct
      measurement of enzyme activity and from studies on phenotypic rescue of
      Escherichia coli. However, the amino-terminal residues are dispensable for this
      activity and the boundary of the active endonuclease lies at this end between
      positions 61 and 80.

PMID- 9525291
TI  - Promoter effect of medroxyprogesterone acetate (MPA) in N-methyl-N-nitrosourea
      (MNU) induced mammary tumors in BALB/c mice.
AB  - The promoter effect of medroxyprogesterone acetate (MPA) on mammary
      carcinogenesis in female BALB/c mice was investigated using methylnitrosourea
      (MNU) as initiator. Nine out of 43 animals developed mammary carcinomas in the
      group treated with MNU (50 mg/kg) and MPA (administration of 40 mg every 3
      months) starting 1 week after MNU administration. No tumors appeared in controls
      receiving only MNU or MPA during the time course of the experiment (9 months).
      The tumors were lobular adenocarcinomas showing different degrees of squamous
      differentiation with low or undetectable estrogen and progesterone receptors, and
      expressing epidermal growth factor receptors. These results support the
      hypothesis that MPA promotes the growth of MNU induced lesions.

PMID- 9525292
TI  - Re: London,S.J. et al. (1997) Genetic polymorphism of CYP2D6 and lung cancer risk
      in African-Americans and Caucasians in Los Angeles County. Carcinogenesis, 18,
      1203-1214.

PMID- 9525293
TI  - Central sleep apnoea and heart failure (Part I).
AB  - Central sleep apnoea (CSA) in congestive heart failure is sleep state dependent
      and occurs typically in stages I and II of non-REM sleep. The pre-requisites are
      hypocapnia and some prolongation of the circulation time. It is not certain
      whether abnormalities in after-discharge activity in the brainstem are also
      important. The presence of CSA in patients with left ventricular dysfunction is a
      poor prognostic sign and associated with a higher mortality in that group
      compared to age, sex and ejection fraction matched patients with congestive
      cardiac failure alone. It is reasonable to speculate that the CSA causes an
      increase in sympathetic nervous system activity which would maintain afterload at
      a high level or tend to increase it with time. The application of a high
      afterload to an impaired left ventricle leads over time to a further reduction in
      ejection fraction. From other studies, particularly ACE inhibitor studies, it is
      known that ejection fraction and prognosis are almost linearly related. It could
      therefore be said that once CSA has developed it may lead to a vicious circle of
      increasing afterload and further reduction in ejection fraction, causing
      worsening CSA and further increases in afterload. A number of treatments have
      been shown to be of benefit: supplemental nocturnal oxygen therapy, acetazolamide
      and nasal CPAP therapy have all been shown to reduce CSA. In addition nasal
      continuous positive airways pressure (CPAP) has been shown by two groups in
      Canada to also improve ejection fraction. The beneficial effects on ejection
      fraction in particular, persist after the treatment has been withdrawn, which
      suggests either remodelling of the left ventricular musculature or a resetting of
      the baseline sympathetic nervous system activity. The impressive increase in
      ejection fraction due to three months nasal CPAP therapy in one study (an average
      35% increase) is both dramatic and exciting for the future. It is reasonable to
      expect improvement in prognosis for patients with CCF whose ejection fraction
      rises with CPAP treatment. Finally, only a limited number of studies have been
      published. Unfortunately the impressive results from Canada have not yet been
      reproduced in other centres around the world.

PMID- 9525294
TI  - Surgical results of 40 patients with malignant tracheobronchial lesions.
AB  - The objective of this study was to evaluate the results of
      tracheobronchoplastyperformed on a variety of malignant diseases which involved
      the tracheobronchus. Between July 1988 and March 1996 tracheobronchial surgery
      was performed on 40 patients who had a variety of malignant diseases. The primary
      diseases were bronchogenic carcinoma (n=26), tracheobronchial tumour (n=5),
      thyroid cancer (n=6), and oesophageal cancer (n=3). Operative procedures that
      were performed on the tracheobronchus were sleeve lobectomy (n=22) or
      bilobectomies (n=5), sleeve pneumonectomy (n=3), sleeve resection of trachea
      (n=7) and bronchus (n=3). There was one postoperative death with a mortality rate
      of 2.5%. However, there were no significant postoperative complications apart
      from the one postoperative death; one patient developed a bronchopleural fistula
      and empyema. In lung cancer patients, the 2 year survival rate was 47.3%, and one
      (3.8%) local tumour recurrence. Four of five patients who had tracheobronchial
      tumours were alive and free from disease during 2-6 year follow-up period. One
      patient who had malignant fibrous histiocytoma died of brain metastasis 6 months
      after the operation. Among six patients whose thyroid cancer involved the
      trachea, one patient survived for 7 years, the other five patients were still
      alive and free from disease 2-5 years after the operation. Of the three patients
      whose oesophageal carcinoma involved the tracheobronchus, there was one operative
      death and the others died of tumour recurrence 1 and 2 years, respectively. We
      suggest that tracheobronchoplasty is a safe procedure with low morbidity and
      mortality rates in carefully selected patients with malignant diseases.

PMID- 9525295
TI  - The effects of a specific tachykinin receptor antagonist FK-224 on ozone-induced
      airway hyperresponsiveness and inflammation.
AB  - We have demonstrated previously that tachykinin depletion by capsaicin prevented
      the ozone-induced airway hyperresponsiveness and the bronchial wall oedema in
      guinea pigs. To further clarify the role of neurogenic inflammation in ozone
      induced airway hyperresponsiveness, we investigated the effects of a specific
      tachykinin receptor antagonist (FK-224) in guinea pigs. Animals were
      anaesthetized, tracheostomized and mechanically ventilated. Total pulmonary
      resistance (RL) was calculated from transpulmonary pressure and box flow in a
      plethysmograph. Airway responsiveness was assessed by determining the provocative
      concentration of histamine aerosol that increased RL to twice the baseline value
      (PC200). Animals were injected with either FK-224 (10 mg/kg, dissolved in 0.2
      mL/kg DMSO) or vehicle (0.2 mL/kg DMSO) intravenously, then pre-ozone PC200 was
      determined. Following this measurement, animals were exposed to 3 ppm ozone for
      60 min. Immediately after exposure, the histamine dose response curve was
      evaluated again. Bronchoalveolar lavage (BAL) was performed in animals treated
      with FK-224 or vehicle. In animals treated with vehicle, ozone exposure caused
      significant decrease in PC200 and moderate increase in neutrophils in BAL fluid.
      FK-224 pre-treatment significantly inhibited ozone-induced hyperresponsiveness.
      Neutrophils in BAL fluid did not significantly increase after ozone exposure in
      animals treated with FK-224. By contrast, the degree of epithelial desquamation
      did not differ significantly between the two groups. We conclude that neurogenic
      inflammation caused by tachykinin release may be responsible for ozone-induced
      bronchial hyperresponsiveness, and that tachykinins may play a role in the
      initiation of airway inflammation.

PMID- 9525296
TI  - Role of sensory innervation and mast cells in neurogenic plasma protein exudation
      into the airway lumen.
AB  - Neurogenic inflammation in the airways involves both mucosal oedema and plasma
      protein exudation into the airway lumen. We aimed to investigate the mechanism of
      exudation of plasma proteins into the airway lumen. Neurogenic inflammation was
      induced in anaesthetized Sprague-Dawley rats by electrical stimulation of both
      vagal nerves at 20 V, 10 Hz, 5 ms. Vascular permeability was measured as 125I
      albumin extravasation into both the airway wall and tracheobronchial lavage
      fluid. Following vagal stimulation, tracheobronchial lavages were analysed for
      albumin, total protein, histamine, immunoreactive substance P (SP), and
      immunoreactive calcitonin gene-related peptide (CGRP). Vagal stimulation rapidly
      increased vascular permeability in the airway mucosa and induced exudation of
      plasma proteins into the tracheobronchial fluid. Pre-treatment with capsaicin
      inhibited both neurogenic vascular permeability and movement of albumin into the
      airway lumen. SP and CGRP were detectable in basal lavages (1.37+/-0.12 ng/mL and
      2.17+/-0.21 ng/mL, respectively) and the concentration of SP fell by 43%
      following treatment with capsaicin. Following vagal stimulation, concentrations
      of both SP and CGRP decreased significantly. Although basal tracheobronchial
      lavages contained histamine, vagal stimulation did not increase the histamine
      concentration. These results indicate that both neurogenic vascular permeability
      and plasma protein exudation into the airway lumen results from activation of
      capsaicin-sensitive sensory nerves and the reaction is not associated with mast
      cell activation.

PMID- 9525298
TI  - Thromboxane inhibition and monocrotaline-induced pulmonary hypertension in rats.
AB  - Monocrotaline (MCT)-induced pulmonary hypertension (PH) is a useful model for the
      investigation of this disorder in humans. The role of thrombocytes in the genesis
      of PH has already been addressed; however, the exact mechanism by which they
      induce PH remains to be elucidated. We investigated the effects of a thromboxane
      A2 (TXA2) synthase inhibitor (OKY-046) and a TXA2/prostaglandin H2 (PGH2)
      receptor antagonist (ONO-8809) on the development of MCT-induced PH. A single
      dose of MCT (60 mg/kg bodyweight; BW) was injected subcutaneously in Wistar rats
      24 h after the administration of OKY-046 or ONO-8809. The TXA2 inhibitors were
      administered by gavage daily for 3 weeks. Urinary excretion of eicosanoids was
      determined by radioimmunoassay. At the end of the treatment period, the lungs,
      heart and kidneys were morphologically examined. The per cent medial thickness of
      the muscular pulmonary arteries (%MT) and the ratio of the right to the left
      ventricular mass including the septum (RV/LV + S) increased significantly in MCT
      treated rats compared with the control rats. The %MT was attenuated by the
      administration of ONO-8809. Either OKY-046 or ONO-8809 attenuated the increase in
      RV/LV + S. In addition, both TXA2 inhibitors reduced urinary excretion of 11
      dehydro-TXB2, particularly during the early phase of PH, suggesting that platelet
      aggregation was reduced. These findings suggest that the inhibition of TXA2 by
      synthase inhibition or receptor antagonism reduces or delays the development of
      MCT-induced PH in rats, probably by inhibiting platelet aggregation.

PMID- 9525299
TI  - Successful removal of a 12 year long intrabronchial fishbone through fibreoptic
      bronchoscopy.
AB  - We report a 54 year old male with an intrabronchial fishbone that had been
      impacted for 12 years and presented as recurrent pneumonia of the right lower
      lobe. The fishbone was successfully removed by fibreoptic bronchoscopy.

PMID- 9525297
TI  - Prospective study of corticosteroid as an adjunct in the treatment of
      endobronchial tuberculosis in adults.
AB  - Although endobronchial tuberculosis frequently causes bronchial stenosis, there
      are no specific therapies to prevent the sequelae. The use of corticosteroids
      remains controversial and there have been no prospective comparative studies
      about the effectiveness of corticosteroids. This study was undertaken in order to
      determine the effectiveness of corticosteroids in the prevention of complications
      of endobronchial tuberculosis. Thirty-four patients with endobronchial
      tuberculosis who were admitted to Chung-Ang University hospital from March 1991
      to December 1995 were evaluated prospectively to determine the effect of
      corticosteroid in the treatment of endobronchial tuberculosis. All patients were
      randomly divided into two groups: group 1 (n=17, anti-tuberculosis chemotherapy
      only) and group 2 (n=17, combining anti-tuberculosis chemotherapy with oral
      corticosteroid). Serial bronchoscopies, pulmonary function tests and chest
      roentgenograms were analyzed every 2 months until the complete resolution of
      endobronchial tuberculosis. Before treatment commenced there were no significant
      differences between the two groups with respect to sex, mean age, pulmonary
      function, chest roentgenogram and morphologic patterns of endobronchial lesion.
      After treatment, the healing rate of bronchoscopic findings and changes in
      pulmonary function showed no significant differences between the two groups.
      Radiologic improvements were observed in all eight patients (five in group 1 and
      three in group 2) with segmental atelectasis on chest roentgenograms after 2
      months of treatment. This study suggests that corticosteroid therapy would not
      influence the outcome of endobronchial tuberculosis and that prompt treatment
      with early diagnosis, before formation of fibrosis would be necessary to prevent
      complications of endobronchial tuberculosis, such as bronchostenosis.

PMID- 9525300
TI  - Progressive interstitial pneumonia associated with myelodysplastic syndrome:
      implication of superoxide hyperproduction by neutrophils.
AB  - Interstitial pneumonia and aseptic neutrophilic infiltration in the lung are rare
      pulmonary manifestations of myelodysplastic syndrome (MDS). We report a patient
      with progressive interstitial pneumonia associated with MDS. Histological
      examination of the lung revealed infiltration of atypical haematopoietic cells
      associated with MDS and diffuse alveolitis with honeycombing. Neutrophils
      obtained from the patient showed superoxide hyperproduction after stimulation
      with phagocytosis and phorbol myristate acetate, which might be attributed to the
      pathogenesis of interstitial pneumonia.

PMID- 9525301
TI  - Large cell carcinoma of the lung metastatic to nuchal muscle.
AB  - Clinically apparent hematogenous skeletal muscle metastases from lung cancer are
      extremely rare. We present a 72-year-old man with a large cell lung carcinoma
      metastatic to nuchal muscle. Cervical computed tomography (CT) and magnetic
      resonance imaging (MRI) revealed the presence of a well-defined mass in the left
      splenius capitis muscle. A percutaneous needle biopsy was performed to establish
      a diagnosis. Localized skeletal muscle swelling may rarely prove to be metastases
      in patients with lung cancer, but should be investigated in the case of muscle
      swelling.

PMID- 9525302
TI  - The US Lung Health Study.
AB  - The US Lung Health Study was a randomized clinical trial carried out in 10
      clinical centres in the United States of America and Canada that enrolled 5887
      male and female smokers age 35-60 years with early chronic obstructive pulmonary
      disease (COPD). Its purpose was to determine whether a programme incorporating
      smoking intervention and use of an inhaled bronchodilator (ipratropium bromide)
      can slow the rate of decline in the forced expiratory volume in one second (FEV1)
      in middle aged smokers with early COPD. Participants were randomized with equal
      probability into three groups: (i) smoking intervention plus bronchodilator; (ii)
      smoking intervention plus placebo; or (iii) no intervention. The primary outcome
      was rate of change and cumulative change in FEV1 over a 5 year period. The
      primary finding was that the use of the bronchodilator did not influence the long
      term decline in FEV1. However, the aggressive smoking intervention programme
      significantly reduced the age-related decline in FEV1.

PMID- 9525303
TI  - Chronic cough.

PMID- 9525304
TI  - Bronchodilator therapy for chronic obstructive pulmonary disease.
AB  - Chronic obstructive pulmonary disease (COPD) is a heterogeneous group of diseases
      characterized by cough, sputum production, dyspnoea, airflow limitation and
      bronchial hyperreactivity. The airflow limitation declines progressively and is
      irreversible or partially reversible. Bronchodilator therapy is prescribed to
      relieve the symptoms, reverse airway obstruction and hopefully slow the rate of
      disease progression and decelerate the decline in pulmonary function. During
      acute exacerbation, inhalation of beta2-agonists remain the therapy of choice.
      The usefulness of anticholinergic inhalation in acute attacks is investigated in
      order to determine if a higher dose and more frequent administration have same
      benefit as beta2-agonists inhalation. Theophylline is usually given orally as a
      sustained release formulation for chronic maintenance therapy. Some patients may
      benefit from theophylline infusion during an acute phase when appropriately used;
      however, sympathomimetic agents fail to produce adequate bronchodilation. During
      interim periods of stability, inhalation of ipratropium bromide has increased in
      popularity as a regular long-term bronchodilator therapy. Although ipratropium
      and beta2-agonists are equally efficacious when the dosage is adequate enough, a
      combination of both provides a rapid onset of action of the adrenergic agents and
      a prolonged action of the anticholinergic. Furthermore, this combination can be
      given in a reduced dose, thereby avoiding side-effects. Inhalation techniques can
      influence the efficacy of bronchodilator therapy. For severe dyspnoeic patients
      or patients with poor technique of co-ordination with metered-dose inhaler (MDI),
      attachment of a spacer to the MDI or using a nebulizer will overcome these
      difficulties. Bronchodilator therapy can not prevent the development of COPD or
      slow down the decline of pulmonary function, other interventions should be
      included in a comprehensive management programme.

PMID- 9525305
TI  - Growth factors gene delivery to enhance grafting.

PMID- 9525306
TI  - Circumventing adenovirus immune response to achieve long-term correction of
      genetic diseases.

PMID- 9525307
TI  - Construction of vectors expressing bioactive heterodimeric and single-chain
      murine interleukin-12 for gene therapy.
AB  - It has been well demonstrated that interleukin-12 (IL-12) could be useful to
      defend against a variety of pathogens, to suppress tumor growth and metastasis,
      and even to be employed as an adjuvant of vaccines to enhance beneficial type 1 T
      helper (Th1) cell response over detrimental type 2 T helper (Th2) cell responses.
      To apply IL-12 genes in gene therapy such as a DNA vaccine, a pIL-12 vector was
      constructed that contained two cytomegalovirus (CMV) promoters to drive the
      expression of p35 and p40 subunits, respectively. In addition, a pscIL-12 vector
      was designed with a linker to fuse p35 cDNA with p40 cDNA to produce a single
      chain IL-12 protein, ensuring not only that the expression of p35 and p40
      subunits was equally expressed, but also that no free p40 subunits interfered
      with IL-12 activity. The data suggested pIL-12 could produce a rather high level
      of biologically active IL-12 after transfection of COS cell lines as well as
      C2C12 muscle cell lines, as measured by both concanavalin A blast proliferation
      assay and enzyme-linked immunosorbent assay. Interestingly, the pscIL-12 vector
      could also express a bioactive murine IL-12 fusion protein in vitro. Furthermore,
      in vivo functional studies also demonstrated that mice co-immunized with a pS
      vector expressing the major envelope protein of hepatitis B virus (HBV) and IL-12
      vectors encoding native IL-12 or single-chain IL-12 fusion protein elicited
      higher levels of IgG2a anti-HBs antibody and of Th1-related cytokine. Because p35
      and p40 genes can be expressed in a vector by using a single promoter, pscIL-12
      should be useful in future applications for nucleic acid vaccination or for gene
      therapy against diseases.

PMID- 9525308
TI  - Stable integration of human immunodeficiency virus-based retroviral vectors into
      the chromosomes of nondividing cells.
AB  - Human immunodeficiency virus type 1 (HIV-1)-based vectors are thought to be
      useful for gene transfer into nondividing cells. We examined whether HIV vectors
      can really integrate into the chromosomes of nondividing cells. CD4+HeLa cells
      arrested at the G2 or G1/S phase were incubated with the HIV vector pseudotyped
      with the HIV envelope. The transduction efficiency of the HIV vector in these
      nondividing cells was comparable to that in proliferating cells. Sequencing of
      the polymerase chain reaction-amplified fragments containing the junction sites
      showed that the HIV vector was stably integrated into the chromosomal DNA. It was
      also demonstrated that terminally differentiated human macrophages and
      nonproliferating NT neurons could be transduced by the HIV vector after
      adenovirus-mediated expression of CD4. These results suggest that the HIV vector
      may be useful not only for gene therapy of AIDS but also for a variety of gene
      therapy protocols targeting nondividing cells.

PMID- 9525309
TI  - Transient immunosuppression allows transgene expression following
      readministration of adeno-associated viral vectors.
AB  - Adeno-associated viral (AAV) vectors have much promise in gene therapy. Among the
      many properties that make AAV an ideal vector for gene therapy are its ability to
      infect both dividing and nondividing cells and the longevity of expression in
      tissues such as brain, skeletal muscle, and liver. However, like other viral
      vectors, readministration of vector is limited because of the host's immune
      response to viral components of the vector. Using class I, class II, and CD40
      ligand (CD40L)-deficient mice, we demonstrate that neutralizing antibodies to the
      viral capsid proteins prevent transgene expression following readministration of
      rAAV vectors. Transient immunosuppression of mice by treatment with antibody to
      CD4 at the time of primary infection allowed transgene expression after
      readministration of rAAV vectors to animals. Transient immunosuppression with
      antibody to CD40L had only a modest effect on the efficacy of readministration.
      The ability to readminister virus was inversely correlated with both AAV capsid
      enzyme-linked immunosorbent assay titers and AAV neutralizing antibody titers.
      These studies demonstrate that readministration of rAAV can be accomplished by
      down regulating the anti-AAV immune response and suggest the use of repeated
      administration of rAAV as a viable form of therapy for the treatment of chronic
      diseases.

PMID- 9525310
TI  - Inhibition of human immunodeficiency virus replication and growth advantage of
      CD4+ T cells from HIV-infected individuals that express intracellular antibodies
      against HIV-1 gp120 or Tat.
AB  - Current clinical gene therapy protocols for the treatment of human
      immunodeficiency virus type 1 (HIV-1) infection often involve the ex vivo
      transduction and expansion of CD4+ T cells derived from HIV-positive patients at
      a late stage in their disease (CD4 count <400). These protocols involve the
      transduction of T cells by murine leukemia virus (MLV)-based vectors encoding
      antiviral constructs such as the rev m10 dominant negative mutant or a ribozyme
      directed against the CAP site of HIV-1 RNA. We examined the efficiency and
      stability of transduction of CD4+ T cells derived from HIV-infected patients at
      different stages in the progression of their disease, from seroconversion to
      AIDS. CD4+ T cells from HIV-positive patients and uninfected donors were
      transduced with MLV-based vectors encoding beta-galactosidase and an
      intracellular antibody directed against gp120 (sFv 105) or Tat. (sFvtat1-Ckappa).
      The expression of marker genes and the effects of the antiviral constructs were
      monitored in vitro in unselected transduced CD4+ T cells. Efficiency and
      stability of transduction varied during the course of HIV infection; CD4+ T cells
      derived from asymptomatic patients were transducible at higher efficiencies and
      stabilities than CD4+ T cells from patients with acquired immunodeficiency
      syndrome (AIDS). Expression of the anti-tat intracellular antibody was more
      effective at stably inhibiting HIV-1 replication in transduced cells from HIV
      infected individuals than was sFv 105. The results of this study have important
      implications for the development of a clinically relevant gene therapy for the
      treatment of HIV-1 infection.

PMID- 9525312
TI  - Cationic liposomes enhance adenovirus entry via a pathway independent of the
      fiber receptor and alpha(v)-integrins.
AB  - The ability of adenoviral vectors to mediate efficient gene delivery both in
      vitro and in vivo is limited by the availability of specific cell surface
      receptors and alpha(v)-containing integrins. We tested whether this limitation
      could be overcome by enhancing viral entry with cationic liposomes. In cultured
      vascular smooth muscle cells, delivery of adenoviral vectors in the presence of
      cationic liposomes increased vector-encoded transgene expression up to 20-fold.
      The increase in transgene expression was associated with the formation of
      adenovirus-lipid aggregates and an increase in the amount of vector DNA in the
      cells, suggesting that enhanced viral entry was responsible for the increase in
      gene expression. Treatment of the cells with an RGD-containing peptide or
      adenovirus type 5 fiber protein did not diminish liposome enhancement of
      transgene expression, indicating that liposomes increase viral entry via a
      pathway independent of the fiber receptor and of alpha(v) integrin-assisted
      endocytosis. Liposomes also significantly enhanced transgene expression from
      adenoviral vectors delivered to cells deficient in alpha(v)-containing integrins.
      The magnitude of liposome enhancement of transgene expression in cultured smooth
      muscle cells was greatest during brief periods of virus-cell contact and at low
      concentrations of virus. Despite these promising in vitro results, addition of
      liposomes did not improve in vivo adenoviral gene delivery into injured rat
      carotid arteries. Liposomes can improve adenoviral gene delivery in vitro;
      however, application of this observation to accomplish improved in vivo gene
      delivery remains a challenge.

PMID- 9525311
TI  - Gene therapy with bilirubin-UDP-glucuronosyltransferase in the Gunn rat model of
      Crigler-Najjar syndrome type 1.
AB  - Crigler-Najjar syndrome type 1 (CN type 1) is an autosomal recessive disorder
      characterized by nonhemolytic jaundice resulting from mutations to the gene
      encoding bilirubin-UDP-glucuronosyltransferase (UDPGT). The Gunn rat is an
      accurate animal model of this disease because the bilirubin-UDPGT gene in this
      strain carries a premature stop codon. The primary objective of this study was to
      complement this deficiency in vivo using liver-directed gene therapy. The
      efficiency of adenovirus type 5 (Ad5)-mediated gene transfer to the neonatal rat
      liver was first assessed by intravenous (i.v.) injection of an Ad5 vector
      carrying a nuclear-localized LacZ gene. An Ad5 vector expressing the cDNA
      encoding human bilirubin-UDPGT (Ad5/CMV/hUG-Br1) was then generated and injected
      i.v. into neonatal Gunn rats. Plasma samples were collected and bilirubin levels
      were determined at regular intervals. Although the mean level of bilirubin in
      homozygous Gunn rats 1-2 days after birth was already 14.5-fold higher than that
      of heterozygous siblings, treatment with Ad5/CMV/hUG-Br1 reduced plasma bilirubin
      to normal levels within 1 week. Plasma bilirubin in the treated homozygous rats
      remained normal for 4 weeks before gradually climbing to intermediate levels that
      were approximately half that of untreated homozygotes by 12 weeks. Administration
      of Ad5-mediated gene therapy to neonatal Gunn rats effectively complemented the
      deficiency in bilirubin-UDPGT, resulting in substantial reductions in plasma
      bilirubin over a 3-month period. The efficacy of Ad5-mediated gene therapy in
      neonates suggests that this approach might be effective against other hepatic
      disorders, including autosomal recessive deficiencies in lipid metabolism and
      vascular homeostasis.

PMID- 9525313
TI  - Assessment of the efficacy of in vivo CFTR protein replacement therapy in CF
      mice.
AB  - Cystic Fibrosis (CF) is caused by mutations in the CF gene that lead, for the
      most part, to mislocalization of the protein product, the cystic fibrosis
      transmembrane conductance regulatory (CFTR). CFTR is a chloride channel normally
      situated in the apical membrane of epithelial cells where it contributes to
      transepithelial ion transport. In this study we demonstrated the feasibility of
      in vivo transfer of purified CFTR protein via phospholipid liposomes into the
      apical membrane of nasal epithelia of CFTR knockout mice. Membrane incorporation
      of immunogold-labeled CFTR could be visualized by electron microscopy and
      correction of CF-related defects in ion transport measured by nasal potential
      difference (PD) measurements in about one-third of the animals treated. Although
      these initial results are promising, effectiveness of this therapeutic approach
      appears to be limited by the inefficient incorporation of CFTR into the apical
      epithelial cell membrane.

PMID- 9525314
TI  - Genetically modified human keratinocytes overexpressing PDGF-A enhance the
      performance of a composite skin graft.
AB  - Skin loss due to burns and ulcers is a major medical problem. Bioengineered skin
      substitutes that use cultured keratinocytes as an epidermal layer with or without
      analogues of the dermis are one strategy for skin repair. However, none can
      achieve definitive wound closure, function, or cosmesis comparable to split
      thickness autografts. Moreover, autograft donor sites, which require time to
      heal, may be limited or have attendant problems such as infection or
      functional/cosmetic deficiencies. To determine if the performance of composite
      skin grafts of keratinocytes on a dermal analogue could be enhanced, human
      keratinocytes were genetically modified to overexpress platelet-derived growth
      factor A chain (PDGF-A). Composite grafts of modified keratinocytes seeded onto
      acellular dermis, prepared from cryopreserved cadaver skin, secreted PDGF-AA
      protein in vitro [90 ng/graft (1.5 x 1.5 cm)/24 hr]. To test their performance in
      a wound healing model, composite grafts were transplanted to full-thickness
      excisional wounds on the back of athymic mice. PDGF-A grafts formed a stratified
      differentiated epidermis similar to control grafts. The acellular dermis was
      repopulated with host fibrovascular cells and by day 7, the PDGF-A grafts had
      significantly more cells in the dermis and increased staining for murine collagen
      types I and IV. At this early time point, wound contraction was also
      significantly inhibited in PDGF-A grafts versus control grafts. Thus, PDGF-A
      overexpression improves graft performance during the first critical week after
      transplantation.

PMID- 9525315
TI  - Adenovirus-mediated interleukin-10 gene transfer inhibits post-transplant fibrous
      airway obliteration in an animal model of bronchiolitis obliterans.
AB  - Bronchiolitis obliterans, a form of chronic allograft rejection characterized by
      progressive fibrous obliteration of the airways, is the major obstacle limiting
      prolonged survival of lung transplant recipients. To date, no effective therapy
      against this fatal complication exists. Interleukin-10 (IL-10), an anti
      inflammatory and immunosuppressive cytokine, inhibits various T cell and antigen
      presenting cell functions. We examined the effect of IL-10 in an animal model for
      bronchiolitis obliterans. A heterotopic tracheal transplant model was used. IL-10
      was administered to the recipient either in its recombinant form by osmotic
      minipump or by adenoviral-mediated IL-10 gene transfer (Ad5E1mIL-10). Successful
      gene transfection and expression was confirmed by measuring circulating IL-10
      protein. Tracheal allografts were assessed histologically based on a scoring
      system. IL-10 administration (in recombinant form or by gene transfer) inhibited
      the development of fibrous airway obliteration 3 weeks after transplantation in
      comparison to untreated controls (p < 0.05). This was demonstrated only if the
      delivery was initiated 5 days after transplantation and not if it was started at
      the time of transplantation. A single administration of the gene construct was
      sufficient to achieve the desired effect. We have shown that IL-10 can prevent
      the development of airway fibro-obliteration in this model. Gene transfection at
      a site distant from a graft can be used to produce a desired effect on the graft.
      IL-10 may be of major importance in the control of post-transplant bronchiolitis
      obliterans. The timing of its administration is critical and further studies are
      required to determine the mechanisms underlying the observed effects of IL-10.

PMID- 9525316
TI  - Efficient transfer of genes into murine cardiac grafts by Starburst
      polyamidoamine dendrimers.
AB  - Starburst dendrimer, a structurally defined, spherical macromolecule composed of
      repeating polyamidoamino subunits, was investigated to augment plasmid-mediated
      gene transfer efficiency in a murine cardiac transplantation model. The grafts
      were directly injected with naked pCH110, a plasmid encoding beta-galactosidase
      (beta-Gal), or pCH110-dendrimer complex, and reporter gene expression determined
      by X-Gal staining. The grafts injected with pCH110-dendrimer demonstrated
      widespread and extended beta-Gal expression in both myocytes and the graft
      infiltrating cells from 7 to 28 days, compared to the grafts injected with naked
      pCH110 that expressed beta-Gal only in myocytes for less than 14 days. p alphaMHC
      vIL-10, as plasmid encoding viral interleukin-10 (vIL-10) under the control of
      alpha-myosin heavy chain promoter, was able to prolong allograft survival from
      13.9 +/- 0.9 days to 21.4 +/- 2.3 days (p < 0.005). When dendrimer G5EDA was used
      with p alphaMHC-vIL-10, 60-fold less DNA resulted in significant prolongation of
      graft survival to 38.6 +/- 4.7 days (p < 0.0005). The dose of DNA, the charge
      ratio of DNA to dendrimer, and the size generation of the dendrimers were all
      determined to be critical variables for prolongation of allograft survival in
      this model system. Thus, the use of the Starburst dendrimer dramatically
      increased the efficiency of plasmid-mediated gene transfer and expression.
      Production of immunosuppressive cytokines at higher amounts for longer periods of
      time in a greater expanse of tissue enhanced the immunosuppressive effect and
      prolonged graft survival further.

PMID- 9525317
TI  - Role of integrin expression in adenovirus-mediated gene delivery to the
      intestinal epithelium.
AB  - Adenoviral vectors are being developed for oral delivery of therapeutic genes to
      the intestine. Initial studies in the rat using mucolytics and direct application
      of adenovirus encoded with the interleukin-1 receptor antagonist gene to the
      jejunum produced limited gene expression. The goal of this study was to determine
      the role of integrins in adenovirus-mediated gene delivery to the intestinal
      epithelium. Integrins are involved in cellular differentiation and tight junction
      formation and mediate adenoviral internalization. Results from Caco-2 and IEC-18
      cells suggest that, as enterocytes differentiate, cell-surface integrin
      expression decreases. Pretreatment of Caco-2 cells with RGD peptides reduced
      adenoviral transduction efficiency by 80% in undifferentiated cells and 20% in
      differentiated cells. Both differentiated and undifferentiated IEC-18 cells
      showed a 70% drop in transduction when pretreated with the peptide. Infection
      inhibition studies with monoclonal antibodies further suggest that alpha(v)beta3
      and alpha6beta1 integrins play significant roles in adenoviral internalization in
      the intestine. Expression of integrins in cell culture models of the intestine
      correlated with in vivo expression in intestinal segments. These results indicate
      that the ileum is a prime target for efficient adenovirus-mediated gene transfer
      in the rat. To enhance transduction in differentiated enterocytes (probable
      targets for oral gene delivery), Caco-2 cells were treated with interleukin-1beta
      (a cytokine known to increase integrin expression) prior to administration of the
      virus. Transduction efficiency increased four-fold.

PMID- 9525318
TI  - Lipid-mediated enhancement of transfection by a nonviral integrin-targeting
      vector.
AB  - Nonviral vectors consisting of integrin-targeting peptide/DNA (ID) complexes have
      the potential for widespread application in gene therapy. The transfection
      efficiency of this vector, however, has been limited by endosomal degradation. We
      now report that lipofectin (L) incorporated into the ID complexes enhances
      integrin-mediated transfection, increasing luciferase expression by more than 100
      fold. The transfection efficiency of Lipofectin/Integrin-binding peptide/DNA
      (LID) complexes, assessed by beta-galactosidase reporter gene expression and X
      gal staining, was improved from 1% to 10% to over 50% for three different cell
      lines, and from 0% to approximately 25% in corneal endothelium in vitro.
      Transfection complexes have been optimized with respect to their transfection
      efficiency and we have investigated their structure, function, and mode of
      transfection. Both ID and LID complexes formed particles, unlike the fibrous
      network formed by lipofectin/DNA complexes (LD). Integrin-mediated transfection
      by LID complexes was demonstrated by the substantially lower transfection
      efficiency of LKD complexes in which the integrin-biding peptide was substituted
      for K16 (K). Furthermore, the transfection efficiency of complexes was shown to
      be dependent on the amount of integrin-targeting ligand in the complex. Finally,
      a 34% reduction in integrin-mediated transfection efficiency by LID complexes was
      achieved with a competing monoclonal antibody. The role of lipofectin in LID
      complexes appears, therefore, to be that of a co-factor, enhancing the efficiency
      of integrin-mediated transfection. The mechanism of enhancement is likely to
      involve a reduction in the extent of endosomal degradation of DNA.

PMID- 9525320
TI  - A Phase I study of the transplantation of genetically marked autologous bone
      marrow stromal cells.

PMID- 9525319
TI  - Expression of the human immunodeficiency virus type 1 primer binding sequence
      inhibits HIV-1 replication.
AB  - Optimal targets for anti-human immunodeficiency virus (HIV) moieties are those
      regions of the viral genome that are greatly conserved. The primer binding site
      (PBS) of HIV is an 18-nucleotide sequence complementary to the 3' end of
      tRNA(Lys3) that serves as the primer for HIV-1 reverse transcription. All HIV-1
      isolates analyzed to date contain a PBS complementary to tRNA(Lys3) illustrating
      the conservation of this sequence. We investigated the activity of a hammerhead
      ribozyme targeting the PBS of HIV-1. CEMss cells transduced with retroviral
      vectors containing either the PBS hammerhead ribozyme or its complementary
      sequence (as a control) in the R region of the vector long terminal repeat (LTR)
      were challenged with HIV-1NL4-3. Surprisingly >80% inhibition of HIV-1 production
      was observed with the vector containing the (control) sequence complementary to
      the PBS ribozyme. We propose that the LTR-driven vector transcript containing 18
      nucleotides identical to the HIV-1 PBS may act like an RNA decoy to titrate viral
      proteins such as reverse transcriptase and nucleocapsid away from genuine viral
      transcripts, thus compromising virus replication.

PMID- 9525321
TI  - Effect of recombinant interleukin-1beta on murine CD14 gene expression in vivo.
AB  - Recombinant murine interleukin-1beta (IL-1beta) induced a transient increase in
      plasma levels of CD14 with a peak at 8 h, and this increase in plasma CD14
      antigen was accompanied by increased levels of CD14 messenger ribonucleic acid
      (mRNA) in all organs examined. In most organs, maximal levels of induction were
      obtained after administration of 125 ng of IL-1beta. Moreover, in situ
      hybridization studies revealed that CD14 mRNA was induced in both myeloid cells
      and epithelial cells. Pretreatment of mice with anti-lL-1beta antibodies reduced
      the subsequent induction of plasma levels of CD14 by lipopolysaccharide (LPS) and
      significantly reduced the level of induction of CD14 mRNA in kidney and liver.
      The antibodies did not block LPS mediated induction in lung. Pretreatment with a
      combination of anti-lL-1beta and anti-tumor necrosis factor (TNF) antibodies was
      more effective in reducing LPS mediated induction of plasma CD14 and CD14 mRNA in
      liver than pretreatment with either antibody alone. The combination of anti-lL
      1beta and anti-TNF antibodies had no additional effect in kidney and lung over
      that observed with anti-TNF alone. These studies demonstrate that regulation of
      CD14 gene expression by LPS in vivo involves multiple signals but is mediated, in
      part, by the cytokines IL-1beta and TNF-alpha.

PMID- 9525322
TI  - Hypertonic saline resuscitation diminishes lung injury by suppressing neutrophil
      activation after hemorrhagic shock.
AB  - Hypertonic saline (HS) resuscitation after hemorrhage and sepsis has been shown
      to markedly reduce the development of lung injury in animals, compared with
      traditional resuscitation with lactated Ringer's (LR). These experiments examined
      the effect of HS on lung injury after hemorrhage without sepsis. The effects of
      HS and LR resuscitation on neutrophil trafficking, neutrophil adhesion, and
      neutrophil oxidative burst were studied. METHODS: BALB/c mice were hemorrhaged to
      a mean arterial pressure of 40 torr for 1 h. Animals were resuscitated with shed
      blood and either 4 mL/kg of 7.5% HS or LR in twice the volume of the shed blood.
      Lung histology was examined 24 h after hemorrhage. Lung myeloperoxidase content
      and bronchoalveolar lavage fluid neutrophil counts were obtained. Peripheral
      blood smears were obtained to determine the neutrophil percentage. Peripheral
      blood neutrophil CD11b expression and neutrophil H2O2 production were assayed by
      flow cytometry. RESULTS: HS animals had less lung injury than LR animals. The
      mean myeloperoxidase activity in HS versus LR animals was 1.79+/-1.33 U/100 mg
      versus 3.0+/-1.33 U/100 mg, respectively. The percentage of neutrophils in the
      bronchoalveolar lavage fluid of HS animals (3.8%+/-.8) was significantly less
      than that of LR animals (10.8%+/-2.1). This corresponded to a significantly
      higher peripheral blood neutrophil count in HS animals compared with LR animals,
      41% vs. 20%, respectively. There was no difference in neutrophil expression of
      the CD11b integrin between the HS and LR groups. The neutrophils of LR animals
      had basal H2O2 production that was 107% greater than that of controls; HS
      suppressed this hemorrhage-induced activation by > 60%. HS resuscitation after
      hemorrhagic shock protects against the development of lung injury. This
      protection is due, in part, to suppression of the hemorrhage-induced neutrophil
      oxidative burst. HS resuscitation offers immunomodulatory potential after
      hemorrhagic shock.

PMID- 9525323
TI  - Prostaglandin E1 attenuates cytotoxic mechanisms of primed neutrophils.
AB  - In a recent clinical trial, liposomal prostaglandin E1 (PGE1) improved
      oxygenation, increased compliance, and decreased ventilator dependency in
      patients with adult respiratory distress syndrome (ARDS), thus renewing interest
      in PGE1 as a potential modulator of inflammation. The neutrophil (PMN) is
      believed to play a key role in the development of ARDS. Consequently, we
      investigated the effects of PGE1 on three components of the neutrophil
      inflammatory response: reactive oxygen species (ROS) generation, protease
      release, and surface expression of adhesion molecules. Human neutrophils were
      incubated with PGE1 and then primed with platelet-activating factor (PAF) and
      activation with N-formyl-methionyl-leucylphenylalanine (fMLP). PGE1 at a dose
      range of (10[-8] to 10[-5] M) attenuated primed/activated (PAF/fMLP) PMN
      superoxide anion generation and elastase release. In contrast, PGE1 doses > or
      =10[-5] M were required to attenuate PAF-stimulated neutrophil upregulation of
      CD11b/CD18 adhesion molecules. PGE1 also diminished the duration of the PAF
      induced cytosolic calcium (Ca2+) flux. Our results suggest that plasma levels of
      PGE1 attained in patients with ARDS may attenuate ROS and protease neutrophil
      cytotoxicity but may not effectively block PMN-endothelial cell (EC) adhesion.
      This attenuation may occur through abrogation of the Ca2+ influx.

PMID- 9525324
TI  - Endothelin (ET)-1 induced mucosal damage in the rat small intestine: role of
      ET(A) receptors.
AB  - The role of endothelin (ET)-1 as a mediator of small intestinal mucosal perfusion
      failure and tissue damage was investigated in the rat using intravital
      fluorescence videomicroscopy. The effects of intravenous infusion of ET-1 (3
      nmol/kg) on functional capillary density, mucosal thickness, and the degree of
      mucosal damage were evaluated. Administration of ET-1 caused pronounced mucosal
      injury with a significant reduction of mucosal thickness compared with vehicle
      treated control animals. Concomitantly, villous functional capillary density was
      markedly reduced 30 and 90 min after the infusion of ET-1. ET(A) receptor
      blockade by pretreatment with BQ 610 or with the novel ET(A) receptor antagonist
      ETR-P1/FL peptide prevented ET-1 induced capillary perfusion failure and mucosal
      damage. In contrast, the ET(B) receptor antagonist IRL 1038 was not effective.
      These results indicate that, acting via the ET(A) receptor, elevated levels of
      circulating ET-1 under various pathophysiological conditions, such as septic or
      hemorrhagic shock, might impair nutritive perfusion of the intestinal mucosa and
      contribute to tissue injury.

PMID- 9525325
TI  - Mesenteric and skeletal muscle microvascular responsiveness in subacute sepsis.
AB  - This study was performed to assess the effects of subacute sepsis in rats on the
      in vitro reactivity of arterioles (internal diameter, 100-150 microm) to alpha1-
      and alpha2-adrenergic stimulation and to angiotensin II. Male Sprague-Dawley rats
      were rendered septic by intraperitoneal implantation of a gelatin capsule
      containing sterile rat feces and 1 x 10(6) viable colony forming units of
      Escherichia coli. Control rats underwent sham laparotomy and implantation of a
      gelatin capsule containing only sterile feces. In vitro reactivity of arterioles
      from mesentery and skeletal muscle were studied 48 h later in a pressurized (50
      mmHg) no flow state using videomicroscopy. Subacute sepsis decreased the
      contractile response of nonprecontracted microvessels from both anatomical sites
      to phenylephrine (both p < .01 versus control) and blunted the relaxation
      response to staurosporine (both p < .01), an inhibitor of protein kinase C. The
      small contraction to angiotensin II of mesenteric vessels was inhibited by sepsis
      (p < .05) but was unaltered in the skeletal muscle microcirculation. In the
      precontracted mesenteric microvessels from septic rats, endothelium-dependent
      relaxation to clonidine and to adenosine 5'-diphosphate were decreased (both p <
      .01 versus control), whereas in skeletal muscle microvessels, clonidine and
      adenosine 5'-diphosphate elicited constriction (both p < .01). Relaxation to the
      endothelium independent vasodilators sodium nitroprusside and pinacidil was
      preserved across all vessels. In conclusion, mesenteric and skeletal muscle
      microvascular responses to angiotensin II and alpha1- and alpha2-adrenergic
      stimulation are altered in subacute sepsis. This may in part lead to systemic
      hypotension and altered organ perfusion during states of chronic sepsis.

PMID- 9525326
TI  - Soluble glucan protects against endotoxin shock in the rat: the role of the
      scavenger receptor.
AB  - Soluble carboxymethyl-b-1,3-glucan (CMG), a possible ligand for scavenger
      receptors, has macrophage-activating action but lacks the granulomatose
      inflammatory side effect: it is a promising immunomodulator that may mitigate the
      severity of sepsis. This motivated us to study in rats the effect of CMG (25
      mg/kg), injected into the tail vein at 48 and 24 h prior to the administration of
      5 mg/kg Escherichia coli 0127.B8 endotoxin on survival, hemodynamic condition,
      and, in vitro, on the chemiluminescence of PMNs and macrophages, and on
      macrophagal tumor necrosis factor (TNF) production. Acetylated low density
      lipoprotein (AcLDL) clearance in vivo and in vitro binding to macrophages was
      used to study scavenger receptor function. In the nonpretreated group 9 of 10
      rats died during the first 24 h after endotoxin, but all CMG-pretreated rats
      survived. CMG-pretreatment prevented severe decreases in cardiac output and blood
      pressure after endotoxin. Chemiluminescence of macrophages and PMNs from CMG
      pretreated rats was about two times less (p < .05) than that from nonpretreated
      ones; the endotoxin induced TNF production by macrophages also decreased.
      Pretreatment with CMG increased, but coinjection of CMG and AcLDL decreased the
      AcLDL clearance, while coinjection of endotoxin and AcLDL decreased the survival
      rate. In vitro AcLDL uptake by macrophages decreased after coinjection with CMG.
      Our results thus showed that CMG was protective in rat endotoxin shock, which
      seemed partly connected with enhancement of endotoxin clearance through scavenger
      receptors and to decreased TNF production.

PMID- 9525327
TI  - Protein kinase C activity is increased in rat heart during the early hyperdynamic
      phase of sepsis.
AB  - Changes in protein kinase C (PKC) (calcium- and phospholipid-dependent protein
      kinase) activity in rat heart during different cardiodynamic phases of sepsis
      were studied in an attempt to understand the pathophysiology of altered
      myocardial function during sepsis. Sepsis was induced by cecal ligation and
      puncture. Experiments were divided into three groups: control, early sepsis, and
      late sepsis. Early and late sepsis refers to those animals sacrificed at 9 and 18
      h, respectively, after cecal ligation and puncture. Cardiac PKC was extracted and
      partially purified by ammonium sulfate fractionation and diethylaminoethyl
      cellulose chromatography. PKC activity was assayed on the basis of the rate of
      incorporation of 32P from [gamma-32P]adenosine triphosphate into histone. The
      results show that during early sepsis, cytosolic PKC activity was increased by 42
      73%, whereas membrane associated PKC activity was unchanged. During late sepsis,
      both cytosolic and membrane associated PKC activities remained unchanged. Kinetic
      analysis of the data on cytosolic PKC during the early phase of sepsis reveals
      that the Vmax (maximal velocity) values for Ca2+, phosphatidylserine, and
      diacylglycerol were increased by 58, 42, and 50%, respectively, with no changes
      in their Km (substrate concentration required for half-maximal enzyme activity)
      values. These data indicate that cytosolic PKC activity was activated in rat
      heart during the early hyperdynamic phase of sepsis. Because PKC mediated
      phosphorylation plays an important role in regulating myocardial contractility,
      an activation in cytosolic PKC may contribute to the development of a
      hypercardiodynamic state during the early phase of sepsis.

PMID- 9525329
TI  - Interleukin-1 and interleukin-6 mediated skeletal muscle arteriolar vasodilation:
      in vitro versus in vivo studies.
AB  - Interleukin (IL) 1 and IL-6 have been implicated in the decreased systemic
      vascular resistance of septic shock; however, their sites of action and
      underlying mechanisms remain unclear. This study determined the effects of IL-1
      and IL-6 on rat skeletal muscle arterioles using both in vitro and in vivo
      preparations. In the in vitro preparation, first order cremasteric arterioles
      were isolated from rats, cannulated with micropipettes, pressurized to 70 mmHg,
      superfused with physiologic saline solution, and allowed to achieve spontaneous
      basal tone in the absence of intraluminal flow. In the in vivo preparation, the
      cremaster muscle of anesthetized rats was surgically opened, secured as a flat
      sheet over an optical pedestal, and superfused with physiologic saline solution.
      Responses of third order arterioles were studied using transillumination video
      microscopy. In both arteriolar preparations, vessel diameter and phenylephrine
      (PE) responsiveness were assessed before and after cytokine exposure and washout.
      In vitro exposure of IL-1 (20 ng/mL (n=8) or 60 ng/mL (n=4)) or IL-6 (500 U/mL
      (n=2) or 1,000 U/mL (n=4)) for 1 h did not cause arteriolar vasodilation or
      change in PE responsiveness. However, during a 1 h in vivo exposure of IL-1 (.01,
      .1, 1.0, or 20 ng/mL), arteriolar diameter increased from 47+/-2 to 58+/-2% of
      maximum diameter (Dmax) (n=14, p < .0001), from 45+/-2 to 69+/-3% of Dmax (n=14,
      p < .0001), from 45+/-3 to 96+/-2% of Dmax (n=8, p < .0001), and from 47+/-4 to
      96+/-1% of Dmax (n=14, p < .0001), respectively. Cytokine washout resulted in
      arteriolar return to basal diameter. Cytokine exposure and washout did not affect
      arteriolar PE responsiveness. In vivo exposure of IL-6 (10, 50, or 250 U/mL) for
      1 h increased diameter from 47+/-2 to 57+/-2% of Dmax (n=14, p < .0001), from
      46+/-2 to 75+/-3% of Dmax (n=14, p < .0001), and from 46+/-2 to 68+/-4% of Dmax
      (n=15, p < .0001), respectively. After washout of IL-6 (10, 50, or 250 U/mL),
      arteriolar dilation persisted, from 16.3+/-.5 to 20.1+/-1.4 microm (n=14, p <
      .003), from 16.1+/-.4 to 20.1+/-.6 microm (n=14, p < .0001), and from 17.7+/-.4
      to 22.5+/-.8 microm (n=15, p < .0001), respectively. There was no change in PE
      responsiveness. These data indicate that the cytokines IL-1 and IL-6 are potent
      dilating agents for skeletal muscle resistance vessels under in vivo conditions.
      However, given that IL-1 and IL-6 are ineffective in causing relaxation of
      similar arterioles under isolated in vitro conditions, it is suggested that IL-1
      and IL-6 interact with parenchymal or intravascular factors to elicit arteriolar
      relaxation.

PMID- 9525328
TI  - Inhibition of nitric oxide synthesis aggravates myocardial ischemia in
      hemorrhagic shock in constant pressure model.
AB  - In hemorrhagic shock (HS), nitric oxide synthase (NOS) inhibitor is known to
      increase blood pressure and prolong survival time. On the other hand, NOS
      inhibitor decreases coronary flow and worsens myocardial ischemia. Therefore, we
      hypothesized that the beneficial effect of NOS inhibitor is attributable to the
      increased coronary perfusion pressure and that it outcompetes the coronary
      vasodilating effects of nitric oxide. To investigate the direct effect of NOS
      inhibitor on the regulation of coronary circulation and the induction of
      myocardial ischemia in HS, we used a canine model at a constant aortic pressure
      of 40 mmHg with an aortic reservoir. In seven dogs, intravenous administration of
      Nomega-nitro-L-arginine methyl ester (L-NAME, 30 mg/kg) at 10 min after induction
      of HS increased both systemic and coronary vascular resistances and further
      increased the serum catecholamine concentration at 10 min after L-NAME. In
      another 14 dogs, the beating hearts were rapidly cross-sectioned (120 ms) and
      freeze clamped (-190 degrees C) by a specially developed sampling device after 10
      min of HS. Transmurally distributed myocardial ischemia was visualized by the
      enhanced reduced nicotinamide adenine dinucleotide fluorescence, which was
      significantly increased with L-NAME (n=7). Chemical analysis revealed a decrease
      in the myocardial ATP concentration with L-NAME in the subendocardial ischemic
      region in HS. In conclusion, with the use of an aortic reservoir to keep the
      aortic pressure constant in HS, NOS blockade significantly worsened myocardial
      ischemia by decreasing coronary flow and augmenting the serum catecholamine
      concentration.

PMID- 9525330
TI  - L-propionyl carnitine, an endogenous ester in fatty acid metabolism, exerts anti
      shock and endothelial protective effects in rat splanchnic ischemia-reperfusion
      injury.
AB  - Splanchnic artery occlusion (SAO) results in a severe form of circulatory shock
      in which oxygen-derived free radicals play an important role. L-Propionyl
      carnitine (LPC), an endogenous ester that plays a crucial role in cellular fatty
      acid oxidation and metabolism, has been shown to exert a protective effect in
      myocardial ischemia/reperfusion injury. Our purpose was to investigate the
      effects of LPC in an SAO model of ischemia/reperfusion injury. Pentobarbital
      anesthetized rats were subjected to 60 min of SAO followed by 120 min of
      reperfusion. An intravenous bolus of LPC (200 microg/kg) administered 2 min
      before reperfusion prolonged survival time (116+/-4 vs. 81+/-3 min in 1 mL/kg .9%
      NaCl vehicle, p < .01), increased survival rate (88 vs. 13.6%, p < .01), and
      attenuated the percent increase in hematocrits (27+/4% vs. 43+/-3%, p < .05), and
      the increases in tissue myeloperoxidase activity (1.76+/-.4 U/100 mg vs. 3.79+/
      .2 U/100 mg, p < .05). In addition, LPC increased mean arterial blood pressures
      at 60 min (p < .05), 80 min (p < .05), 100 min (p < .05), and 120 min (p < .05)
      postreperfusion. Moreover, LPC markedly attenuated splanchnic artery endothelial
      dysfunction induced by SAO ischemia/reperfusion injury (maximal vasorelaxation to
      ACh, 74+/-2.7% vs. 57+/-1.9% in vehicle, p < .01). In this murine SAO model of
      ischemia/reperfusion injury, LPC affords significant protection that may be
      achieved through inhibiting leukocyte infiltration into intestinal tissue and
      preserving endothelial function, thereby decreasing microvascular permeability
      and maintaining tissue perfusion.

PMID- 9525331
TI  - Modulation of resuscitative effect of diaspirin cross-linked hemoglobin by L-NAME
      in rats.
AB  - Diaspirin Cross-linked Hemoglobin (DCLHb), a hemoglobin-based oxygen carrier,
      improves regional blood circulation and systemic hemodynamics in normal and
      hemorrhaged rats. The action of DCLHb is partly mediated by its scavenging effect
      on nitric oxide. This study was undertaken to determine the effect of DCLHb on
      nitric oxide mechanism in hemorrhagic conditions. We studied the modulation of
      cardiovascular effects of DCLHb by a nitric oxide synthase inhibitor, NG-nitro-L
      arginine methyl ester (L-NAME) in hemorrhaged rats. The base deficit, survival
      time, oxygen consumption, and blood circulation to the brain, heart,
      gastrointestinal tract, and kidneys were determined in 1) DCLHb (100 mg/kg,
      intravenously (i.v.), 2) L-NAME (2 mg/kg, i.v.), 3) L-NAME (2 mg/kg, i.v.) +
      DCLHb (100 mg/kg, i.v.), and 4) L-arginine (100 mg/kg/h, i.v.) + DCLHb (100
      mg/kg, i.v.) treated rats. Hemorrhage was induced in urethane-anesthetized male
      rats by bleeding them at a rate of approximately .5 to 1 mL/min, until a mean
      arterial pressure of 35-40 mmHg was achieved. This blood pressure was maintained
      for 30 min. Sham-operated nonhemorrhaged rats survived for >300 min, whereas
      hemorrhaged rats survived for only 85+/-31 min. Hemorrhage significantly
      increased base deficit and decreased oxygen consumption. A significant decrease
      in heart rate, mean arterial pressure, cardiac output, stroke volume, and in
      blood flow to the gastrointestinal tract and kidneys was observed after
      hemorrhage. Resuscitation with DCLHb produced a significant increase in survival
      time, oxygen consumption, heart rate, mean arterial pressure, cardiac output,
      total peripheral resistance, and blood flow to the brain, heart, and kidneys. In
      contrast, resuscitation with L-NAME did not improve base deficit, survival time,
      oxygen consumption, systemic hemodynamics, or regional blood flow. L-arginine
      pretreatment did not affect DCLHb-induced resuscitation of hemorrhaged rats.
      Furthermore, L-NAME (pretreated or co-administered) attenuated the resuscitative
      effect of DCLHb. These data suggest that nitric oxide mechanism may not be the
      only mechanism involved in the resuscitative effect of DCLHb.

PMID- 9525332
TI  - Reduced PAF-acetylhydrolase activity is associated with postinjury multiple organ
      failure. David A. Partrick, Ernest E. Moore, Frederick A. Moore, Walter L. Biffl,
      and Carlton C. Barnett. Shock 7:170-174, 1997.

PMID- 9525333
TI  - The nuclear vitamin D receptor: biological and molecular regulatory properties
      revealed.

PMID- 9525334
TI  - Renal and nonrenal 25-hydroxyvitamin D-1alpha-hydroxylases and their clinical
      significance.

PMID- 9525335
TI  - Persistence of Ca2+-sensing receptor expression in functionally active, long-term
      human parathyroid cell cultures.
AB  - An original human parathyroid cell culture model from uremic patients with IIo
      hyperparathyroidism has been developed, with its main feature being long-term
      functionally active viability up to 5 months, as assessed by persistent
      responsiveness to changes of extracellular Ca2+ concentrations ([Ca2+]e). In
      addition to the inhibitory effect of increasing [Ca2+]e, increasing extracellular
      phosphate exerted a biphasic effect on parathyroid hormone (PTH) secretion. The
      presence of the Ca2+-sensing receptor (CaR), on which depends the response to
      [Ca2+]e and its persistence, has been demonstrated in our culture system both by
      direct detection and by inhibition of its activity. CaR protein was detected by
      Western blot analysis with a specific anti-CaR antibody. CaR gene transcripts
      have been identified by reverse transcription-polymerase chain reaction analysis.
      mRNA (by in situ hybridization) and protein (by immunocytochemistry) expression
      were detected for both CaR and PTH. Adding a specific anti-CaR antibody to the
      medium induced a marked reduction of low [Ca2+]e-stimulated PTH release, which
      decreased to levels equivalent to those obtained in high [Ca2+]e medium. The
      described long-term functionality could be due to several factors, including the
      clustered cell type of culture yielded by our preparation procedure, the growth
      characteristics of hyperplastic uremic tissue, and the use of a phosphate-rich
      medium. The present model, because of its long-term functionality, is a unique
      tool for the exploration of PTH synthesis and secretion and for studies of
      parathyroid cell growth in vitro.

PMID- 9525336
TI  - Do dietary calcium and age explain the controversy surrounding the relationship
      between bone mineral density and vitamin D receptor gene polymorphisms?
AB  - Whether vitamin D receptor (VDR) gene polymorphisms are associated with
      osteoporosis is highly controversial. The relationship between VDR gene
      polymorphisms and bone mineral density (BMD) might, however, be modified by age
      related and/or environmental factors. We studied the potential association
      between BMD and VDR genotypes in females from prepuberty to premenopause and
      prospectively investigated the interaction of VDR genotypes with dietary calcium
      and BMD changes during childhood. Bsm I VDR gene polymorphisms and BMD at the
      lumbar spine (LS) and femur (neck [FN] and midshaft [FS]) were assessed in 369
      healthy Caucasian females, aged 7-56 years (143 prepubertal girls, 54 peri- and
      postpubertal adolescents, and 172 premenopausal adults). Femoral trochanter (FT)
      and distal radius BMD (metaphysis and diaphysis) were also measured in 101 of the
      prepubertal girls who participated in a 1-year, double-blind, randomized study of
      calcium supplementation (850 mg/day) versus placebo on bone mineral mass accrual.
      Among all females, 150 (40.7%) had bb, 167 (45.3%) Bb, and 52 (14%) BB VDR
      genotypes. In prepubertal and adolescent girls altogether, LS BMD (Z scores) was
      associated with VDR genotypes and was significantly lower in BB than in Bb or bb
      subjects. Trends for a similar difference were also detected at the FN level as
      well as on the mean BMD (Z scores) of the three sites measured (LS, FN, and FS).
      By contrast, no BMD differences were detectable among VDR genotypes in the
      adults. In 101 prospectively studied prepubertal girls, calcium supplementation
      significantly increased BMD at most skeletal sites, except LS. After segregation
      for VDR genotypes (40 bb, 47 Bb, and 14 BB), a significant calcium effect was
      present in Bb but not bb girls, whereas in BB girls there was a positive but
      nonsignificant trend for a calcium effect. Moreover, dietary calcium intake was
      significantly correlated with BMD changes at various independent bone sites in Bb
      girls but not in bb girls. In contrast, BMD gain in bb girls appeared to be
      higher than among the other genotypes when the dietary calcium intake was low,
      i.e., in the absence of calcium supplements. BMD was significantly associated
      with VDR gene polymorphisms only before puberty, BB girls having significantly
      lower BMD (Z scores) than the other genotypes. By increasing dietary calcium
      intake, BMD accrual was increased in Bb and possibly BB prepubertal girls,
      whereas bb subjects had the highest spontaneous BMD accrual and remained
      unaffected by calcium supplements. Taking into account complex interactions
      between VDR gene polymorphisms and environmental factors, including calcium
      intake, may thus help to understand the discordant relationships between BMD and
      VDR gene polymorphisms.

PMID- 9525337
TI  - Human trabecular bone cells are able to express both osteoblastic and adipocytic
      phenotype: implications for osteopenic disorders.
AB  - The decrease in bone volume associated with osteoporosis and age-related
      osteopenia is accompanied by increased marrow adipose tissue formation. Reversal
      of this process may provide a novel therapeutic approach for osteopenic
      disorders. We have shown that cells cultured from human trabecular bone are not
      only osteogenic, but are able also to undergo adipocyte differentiation under
      defined culture conditions. Osteoblast differentiation was induced by 1,25
      dihydroxyvitamin D3 (1,25(OH)2D3) and adipocyte differentiation by dexamethasone
      (dex) plus 3-isobutyl-1-methylxanthine (IBMX) treatment. Adipogenesis was
      characterized by lineage-specific enzyme and gene activities, alpha
      glycerophosphate-3-dehydrogenase activity, fatty acid binding protein, aP2 and
      lipoprotein lipase expression. Osteoblastogenesis was assessed by osteoblast
      characteristic 1,25(OH)2D3 induction of alkaline phosphatase activity and
      osteoblast-specific 1,25(OH)2D3-induced osteocalcin synthesis and release. We
      provide evidence for a common pluripotent mesenchymal stem cell that is able
      either to undergo adipogenesis or osteoblastogenesis, using clonal cell lines
      derived from human trabecular bone cell cultures. Adipogenesis can be induced
      also by long chain fatty acids and the thiazolidinedione troglitazone. Dex plus
      IBMX-induced adipogenesis can be inhibited by interleukin-1beta, tumor necrosis
      factor-alpha, and transforming growth factor-beta. Interestingly, and in contrast
      to extramedullary adipocyte differentiation as shown by mouse 3T3L-1 and a human
      liposarcoma SW872 cell line, trabecular bone adipogenesis was unaffected by
      insulin. Also, the formation of fully differentiated adipocytes from trabecular
      bone cells after troglitazone treatment and long chain fatty acids was dependent
      on increased expression of the nuclear hormone receptor peroxisome proliferator
      activated receptor gamma2 caused by dex plus IBMX. Specific inhibition of marrow
      adipogenesis and promotion of osteoblastogenesis of a common precursor cell may
      provide a novel therapeutic approach to the treatment of osteopenic disorders.

PMID- 9525338
TI  - Cartilage-derived morphogenetic proteins and osteogenic protein-1 differentially
      regulate osteogenesis.
AB  - Cartilage-derived morphogenetic proteins-1 and -2 (CDMP-1 and CDMP-2) are members
      of the bone morphogenetic protein (BMP) family, which play important roles in
      embryonic skeletal development. We studied the biological activities of
      recombinant CDMP-1 and CDMP-2 in chondrogenic and osteogenic differentiation and
      investigated their binding properties to type I and type II serine/threonine
      kinase receptors. In vivo, CDMP-1 and CDMP-2 were capable of inducing dose
      dependently de novo cartilage and bone formation in an ectopic implantation
      assay. In vitro studies using primary chondrocyte cultures showed that both CDMP
      1 and CDMP-2 stimulated equally de novo synthesis of proteoglycan aggrecan in a
      concentration-dependent manner. This activity was equipotent when compared with
      osteogenic protein-1 (OP-1). In contrast, CDMPs were less stimulatory than OP-1
      in osteogenic differentiation as evaluated by alkaline phosphatase activity and
      expression levels of bone markers in ATDC5, ROB-C26, and MC3T3-E1 cells. CDMP-2
      was the least osteogenic in these assays. Receptor binding studies of CDMP-1 and
      CDMP-2 revealed that both have affinity for the BMP receptor type IB (BMPR-IB)
      and BMPR-II, and weakly for BMPR-IA. Moreover, using a promoter/reporter
      construct, transcriptional activation signal was transduced by BMPR-IB in the
      presence of BMPR-II upon CDMP-1 and CDMP-2 binding. Our data show that distinct
      members of the BMP family differentially regulate the progression in the
      osteogenic lineage, and this may be due to their selective affinity for specific
      receptor complexes.

PMID- 9525339
TI  - IL-6 mediates the effects of IL-1 or TNF, but not PTHrP or 1,25(OH)2D3, on
      osteoclast-like cell formation in normal human bone marrow cultures.
AB  - A potent interleukin-6 (IL-6) antagonist (Sant 5), which binds tightly to the IL
      6alpha receptor but has impaired gp130 heterodimerization, has been developed
      recently by site-directed mutagenesis of human IL-6. We report here that Sant 5
      inhibits IL-6-stimulated osteoclast-like multinucleated cell (MNC) formation in
      human marrow cultures but also inhibits the stimulatory effects of IL-1 or tumor
      necrosis factor alpha (TNF-alpha in these cultures. We further show that a
      neutralizing antibody to IL-6 also inhibits the stimulatory effects of IL-1 or
      TNF-alpha in these cultures. In contrast, Sant 5 had no effect on parathyroid
      hormone related protein (PTHrP) or 1,25-dihydroxyvitamin D3 stimulated MNC
      formation in human marrow cultures. Transfection of a human marrow stromal cell
      line, which normally induces osteoclast formation through production of IL-6,
      with the Sant 5 cDNA driven by a cytomegalovirus (CMV) promoter blocked the
      capacity of these cells to stimulate osteoclast-like cell formation. These Sant 5
      transfected cells and conditioned media from these cells also inhibited the
      stimulatory effects of the parent cell line on MNC formation. These data suggest
      that IL-6 mediates the effects of IL-1 and TNF on human osteoclast formation, but
      in contrast to murine systems, does not mediate the effects of PTHrP. These data
      further demonstrate that stromal cells transfected with the Sant 5 cDNA can
      constitutively produce high levels of the IL-6 antagonist and inhibit osteoclast
      formation in vitro.

PMID- 9525340
TI  - The mouse mammary tumor cell line, MMT060562, produces prostaglandin E2 and
      leukemia inhibitory factor and supports osteoclast formation in vitro via a
      stromal cell-dependent pathway.
AB  - Osteoclastic bone resorption increases at the site of bone metastasis, but little
      is known about how tumor cells induce osteoclast (OC) recruitment in the bone
      marrow microenvironment. To clarify this point, we examined the effects of
      various mouse tumor cells on OC recruitment using cocultures of tumor cells and
      mouse marrow cells. The mouse mammary tumor cell lines, MMT060562 (MMT), BALB/c
      MC, Jyg-MC(A), or other nonmammary tumor cell lines, LLC and B16, were cocultured
      with mouse marrow cells, and OC recruitment from marrow cells was determined by
      counting the number of tartrate-resistant acid phosphatase-positive
      multinucleated cells (TRAP(+) MNCs) formed. Of the tumor cells examined, MMT and
      BALB/c-MC stimulated OC formation, but other tumor cells did not. OC formation
      with MMT was dependent on the number of MMTs inoculated, and only ten cells per
      well were sufficient to induce OC development. OCs appeared on day 4, and the
      number reached a maximum on days 5-8 and decreased thereafter. TRAP(+) MNCs
      induced by MMT satisfied the major criteria of OCs, such as the presence of
      calcitonin receptors and the ability to resorb calcified tissues. The majority of
      OCs were formed adjacent to the stromal cells, which were positive for alkaline
      phosphatase. When spleen cells were cocultured with MMT, no OCs were formed. In
      contrast, when osteoblastic cells were added to cocultures of spleen cells and
      MMT, many OCs were formed. The cultured media (CM) of MMT induced OC formation in
      mouse marrow cultures. Neither parathyroid hormone-like nor interleukin 1-like
      activity was present in the CM. MMT constitutively produced prostaglandin E2
      (PGE2) and OC formation in cocultures was completely inhibited by indomethacin.
      Fractionation of the CM of MMT by ultrafiltration indicated that the OC-inducing
      activities were present not only in the fraction with molecular weight below 3
      kDa but also in the fraction with molecular weight above 3 kDa. OC-inducing
      activity with high molecular weight was eluted around 50 kDa by Bio-Gel P-60
      column chromatography. The active fractions also possessed leukemia inhibitory
      factor (LIF) activity, and OC-inducing activity of the peak fraction was
      inhibited in the presence of anti-LIF neutralizing antibody. The results of this
      study indicated that MMTs release PGE2 and LIF, which in turn stimulate OC
      formation via a stromal cell-dependent pathway. These culture systems will help
      to clarify the mechanisms by which tumor cells induce OC formation in a bone
      marrow microenvironment.

PMID- 9525341
TI  - Contortrostatin, a homodimeric snake venom disintegrin, is a potent inhibitor of
      osteoclast attachment.
AB  - Disintegrins are small disulfide-rich proteins containing an Arg-Gly-Asp (RGD)
      sequence near their carboxyl terminus. These polypeptides inhibit binding of
      adhesion molecules to their receptors (integrins) on the surface of cells.
      Osteoclasts express integrins, heterodimeric cell surface adhesion receptors,
      that have been shown to be involved in interactions with the extracellular matrix
      (ECM), including attachment to bone and bone resorption. It has recently been
      shown that disintegrins effectively inhibit attachment of osteoclasts to
      components of the ECM and also disrupt osteoclast-mediated bone resorption. Here
      we characterize the effects of contortrostatin (CTS), a novel homodimeric snake
      venom disintegrin, on osteoclast attachment. Plastic dishes coated with CTS were
      able to support osteoclast attachment with a high affinity (EC50,CTS = 86 +/- 6.7
      nM) similar to that of vitronectin (VTN; EC50,VTN = 80 +/- 20 nM). Further, CTS
      was observed to inhibit completely osteoclast attachment to fetal bovine serum
      (FBS; IC50,FBS = 0.36 +/- 0.04 nM) and VTN (IC50,VTN = 0.85 +/- 0.13 nM). We used
      monoclonal antibodies directed against the beta1 (monoclonal antibody [MAb] CD29)
      and beta3 (MAb F11) integrin subunits to explore the mechanism of osteoclast
      attachment to immobilized CTS. Only MAb F11 inhibited attachment to immobilized
      CTS (IC50 = 0.41 +/- 0.12 microg/ml), suggesting that binding to CTS is mediated
      in part by a beta3 integrin, presumably the alpha(v)beta3 VTN receptor. In
      further support of an integrin-mediated mechanism, binding of osteoclasts to CTS
      is inhibited by the RGD peptide, GRGDSP. CTS was also more potent (IC50,FBS =
      0.36 +/- 0.04 nM) at inhibiting osteoclast attachment to FBS-coated wells than
      the monomeric snake venom disintegrin echistatin (IC50,FBS = 8.9 +/- 1.5 nM) or
      VTN (IC50FBS = 97.5 +/- 25.5 nM). Taken together, these data suggest that the
      snake venom disintegrin CTS is a potent inhibitor of beta3 integrin-mediated
      osteoclast attachment, presumably involving the VTN receptor (an alpha[v]beta3
      integrin). Further studies of the mechanism of CTS-osteoclast interactions may
      aid in the design of peptide mimetics to act as antiresorptive agents for the
      treatment of osteoporosis and other skeletal pathology.

PMID- 9525342
TI  - Bone mineral, histomorphometry, and body composition in adults with growth
      hormone receptor deficiency.
AB  - Growth hormone (GH) and insulin-like growth factor I (IGF-I) deficiencies have
      been associated with osteopenia in both children and adults. To examine the
      effects of growth hormone resistance on bone mineral and body composition, we
      studied 11 adults (mean age 30 years) with growth hormone receptor deficiency
      (GHRD, Laron syndrome) and 11 age- and gender-matched controls from Southern
      Ecuador. Bone mineral and body composition were determined by dual-energy X-ray
      absorptiometry. Bone physiology was assessed with biochemical markers of bone
      turnover and dynamic bone histomorphometry. Bone size and body composition
      differed markedly between subjects with GHRD and controls. Affected adults were
      40 cm shorter than controls, had significantly less lean body mass, and had
      increased percent body fat. Bone mineral content and density (BMD) at the spine,
      femoral neck, and whole body were significantly lower in adults with GHRD than in
      controls. Mean BMD Z scores were -1.5 to -1.6 at all sites in affected women and 
      2.2 to -2.3 in men with GHRD. Estimated volumetric bone density (BMAD) at the
      spine and femoral neck, however, was not reduced in GHRD. Spine BMAD was 0.210 +/
      0.025 versus 0.177 +/- 0.021 for affected women versus controls (p < 0.05) and
      0.173 +/- 0.018 versus 0.191 +/- 0.025 for men with GHRD versus normals (p =
      0.31). Urinary pyridinoline concentrations were significantly greater in adults
      with GHRD than in controls, while type I collagen C-telopeptide breakdown
      products and markers of bone formation did not differ. Differences in
      histomorphometry were limited to a reduction in trabecular connectivity; bone
      volume and formation rate were similar to controls. These data confirm the
      importance of the GH/IGF axis in regulating bone size and body composition. The
      contribution of these peptides to the acquisition and maintenance of bone mineral
      is less certain since volumetric bone density was preserved despite low levels of
      IGF-I and IGFBP-3 associated with GH resistance.

PMID- 9525343
TI  - Identification of a novel isoform of mouse dentin matrix protein 1: spatial
      expression in mineralized tissues.
AB  - Dentin matrix protein 1 (Dmp1) is an acidic phosphoprotein first identified by
      cDNA cloning from a rat tooth library. Northern blot hybridization of a variety
      of tissues detected Dmp1 mRNAs only in odontoblasts, suggesting that this protein
      was odontoblast specific. In situ hybridization studies showed expression of Dmp1
      in odontoblasts with transient expression in secretory ameloblasts. The purpose
      of this study was to isolate and characterize a mouse Dmp1 cDNA and determine its
      spatial expression pattern related to other mineralizing tissues. A mouse molar
      cDNA library was screened with a 32P-labeled Dmp1 polymerase chain reaction
      amplification product in order to isolate a full-length clone. DNA sequence
      analysis of the largest mouse Dmp1 cDNA (2802 base pairs [bp]) revealed an open
      reading frame of 1509 nucleotides encoding a 503 amino acid protein with a single
      polyadenylation signal. Comparison with rat and bovine Dmp1 sequence showed high
      homology and the identification of a 45 bp (15 amino acid) insert, representing
      an alternative spliced mRNA. This 45 bp segment was shown to represent a small
      exon by DNA analysis of a mouse genomic Dmp1 clone. In situ hybridization studies
      revealed a much broader Dmp1 tissue expression pattern than previously reported.
      Dmp1 transcripts were detected in the odontoblast and ameloblasts, osteoblasts,
      and cementoblasts. Our data indicate that Dmp1 is alternatively spliced, and the
      primary full-length transcript contains a 45 bp insert which is encoded by a
      small exon. Therefore, Dmp1 is not a tooth-specific protein but rather is
      expressed in a number of mineralizing tissues including enamel, bone, and
      cementum.

PMID- 9525344
TI  - Expression of type X collagen and matrix calcification in three-dimensional
      cultures of immortalized temperature-sensitive chondrocytes derived from adult
      human articular cartilage.
AB  - Chondrocytes isolated from normal adult human articular cartilage were infected
      with a retroviral vector encoding a temperature-sensitive mutant of the simian
      virus 40 large tumor antigen and a linked geneticin (G418)-resistance marker.
      G418-resistant colonies were then isolated, ring-cloned, and expanded in serum
      containing media. Several immortalized chondrocyte cell lines were established
      from the clones that survived, some of which have been maintained in continuous
      culture for over 2 years. Despite serial subcultures and maintenance as
      monolayers, these cells retain expression of markers specific for cells of the
      lineage, namely type II collagen and aggrecan, detected immunocytochemically. We
      also examined the phenotype of three of these immortalized cell lines (designated
      HAC [human articular chondrocyte]) using a pellet culture system, and in this
      report, we present evidence that a prototype of these lines (HAC-F cells)
      expresses markers normally associated with hypertrophic chondrocytes. When HAC-F
      cells were cultivated in centrifuge tubes, for periods of up to 63 days, at 39
      degrees C with mild and intermittent centrifugation they continued to express
      both lineage markers; total type II collagen/pellet remained stable, whereas
      there was a temporal decrease in cartilage-specific glycosaminoglycans content.
      In addition, in the presence of ascorbate but in the absence of a phosphate donor
      or inorganic phosphate supplement, the cells also begin to express a hypertrophic
      phenotype characterized by type X collagen synthesis and extensive mineralization
      of the extracellular matrix in late stage cultures. The mRNA encoding type X
      collagen was detected in the cell pellets by reverse transcriptase polymerase
      chain reaction as early as day 2, and anti-type X collagen immunoreactivity was
      subsequently localized in the matrix. The mineral was characterized by energy
      dispersive X-ray microanalysis as containing calcium (Ca) and phosphorus (P) with
      a Ca:P peak height ratio close to that of mineralized bone tissue. The unexpected
      phenotype of this human chondrocyte cell line provides an interesting opportunity
      for studying chondrocyte maturation in vitro.

PMID- 9525345
TI  - Mechanism of mechanically induced intercellular calcium waves in rabbit articular
      chondrocytes and in HIG-82 synovial cells.
AB  - Intercellular communication through gap junctions allows tissue coordination of
      cell metabolism and sensitivity to extracellular stimuli. Intercellular Ca2+
      signaling was investigated with digital fluorescence video imaging in primary
      cultures of articular chondrocytes and in HIG-82 synovial cells. In both cell
      types, mechanical stimulation of a single cell induced a wave of increased Ca2+
      that was communicated to surrounding cells. Intercellular Ca2+ spreading was
      inhibited by 18alpha-glycyrrhetinic acid, demonstrating the involvement of gap
      junctions in signal propagation. In the absence of extracellular Ca2+, mechanical
      stimulation induced communicated Ca2+ waves similar to controls; however, the
      number of HIG-82 cells recruited decreased significantly. Mechanical stress
      induced Ca2+ influx both in the stimulated chondrocyte and HIG-82 cell, but not
      in the adjacent cells, as assessed by the Mn2+ quenching technique. Treatment of
      cells with thapsigargin and with the phospholipase C (PLC) inhibitor U73122
      blocked mechanically induced signal propagation. These results provide evidence
      that in chondrocytes and in HIG-82 synovial cells, mechanical stimulation
      activates PLC, thus leading to an increase of intracellular inositol 1,4,5
      trisphosphate. The second messenger, by permeating gap junctions, stimulates
      intracellular Ca2+ release in neighboring cells. It is concluded that
      intercellular Ca2+ waves may provide a mechanism to coordinate tissue responses
      in joint physiology.

PMID- 9525346
TI  - Homologous up-regulation of vitamin D receptors is tissue specific in the rat.
AB  - 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) receptors (VDR) are expressed in multiple
      tissues within the body. VDR levels are increased by 1,25(OH)2D3 in intestine and
      kidney and in numerous cell models. The ability of 1,25(OH)2D3 to affect VDR
      levels in other target tissues in vivo was studied by assessing VDR levels by the
      3H-1,25(OH)2D3 binding assay under varied physiological conditions in the rat.
      When compared with vitamin D-deficient (-D) controls, rats raised on a normal
      vitamin D-sufficient (+D) diet showed elevated VDR levels in kidney (391 +/- 53
      vs. 913 +/- 76 fmol/g of tissue;p < 0.05), but not in testis, heart, or lung. Up
      regulation of the VDR also occurred in kidney of +D rats 1 day after a single 100
      ng dose of 1,25(OH)2D3 (454 +/- 43 vs. 746 +/- 113 fmol/mg of DNA; p < 0.05), but
      no changes were seen in intestine, testis, or lung. Because 1,25(OH)2D3-induced
      hypercalcemia may independently affect VDR regulation, 1,25(OH)2D3 was infused
      into -D rats, and normocalcemia was maintained by reduced dietary calcium intake.
      In this model, the renal VDR was again up-regulated (446 +/- 115 vs. 778 +/- 58
      fmol/mg of DNA; p < 0.05), but VDR levels in testis and lung were unaffected.
      Scatchard analysis and tests of 1,25(OH)2D3 dose (1-100 ng/day for 7 days) and
      temporal (100 ng/day for 1-7 days) responsiveness further supported the tissue
      specific nature of the homologous VDR regulation. Assay of VDR levels by L-1
      tosylamido-2-phenylethyl chloromethyl ketone-3H-1,25(OH)2D3 exchange assay ruled
      out differences in endogenous 1,25(OH)2D3 occupancy as the basis for the observed
      differences in VDR regulation. Finally, coidentity of the VDR-like sites in
      kidney versus testis was confirmed by competitive binding analysis comparing
      their relative affinities for 25(OH)D3 versus 1,25(OH)2D3 (30.5 +/- 6.4 vs. 35.6
      +/- 3.6 in kidney and testis, respectively) and by immunoblot analysis using a
      highly specific monoclonal anti-rat VDR antibody. Thus, under a wide variety of
      experimental conditions, homologous up-regulation of the VDR occurs in the rat
      kidney in vivo, but not in several other target tissues which do not regulate
      plasma calcium homeostasis. Moreover, this differential VDR regulation did not
      result from secondary changes in plasma calcium, from differential 1,25(OH)2D3
      responsiveness in the various tissues, nor from differences in endogenous
      1,25(OH)2D3 occupancy of the VDR. These studies thus establish that, in contrast
      to observations in vitro, the widely described phenomenon of homologous VDR up
      regulation in kidney and intestine is not a universal property of 1,25(OH)2D3
      target tissues in vivo in the rat.

PMID- 9525347
TI  - Morphometric X-ray absorptiometry: reference data for vertebral dimensions.
AB  - Vertebral fractures are a common and important consequence of osteoporosis and
      are often identified via morphometric analysis of conventional lateral spine
      radiographs (morphometric radiography or MRX). A new method of performing
      vertebral morphometry using images acquired on dual-energy X-ray absorptiometry
      (DXA) scanners (morphometric X-ray absorptiometry or MXA) has recently been
      developed. In this study, we derive reference data for vertebral heights and
      height ratios using MXA scans as the data source and compare the results with
      previously published MRX studies. One thousand and nineteen Caucasian women (mean
      age 63 years, range 33-86) were recruited. An MXA scan, covering 13 vertebrae
      from L4 to T4, was acquired for each subject on one of four DXA systems located
      at three centers in the U.K. Analysis of variance found statistically significant
      but relatively small differences among centers, machines, and scan modes, and
      therefore data were pooled for reference range calculations. Three vertebral
      heights (anterior, mid, and posterior) were measured and four ratios (wedge, mid
      wedge, and two crush) calculated. These data sets were trimmed using an iterative
      algorithm to remove extreme values assumed to represent deformed vertebrae, then
      mean and SD values were calculated using the remaining data. When the data were
      split by age, a small but statistically significant decrease in vertebral height
      between the sixth and eighth decades was found, but this was not replicated for
      the vertebral height ratios. Marked differences were observed between MXA data
      and MRX, but were comparable to those between different MRX studies. These may
      result from differences in image quality and point placement protocols,
      population differences, differences in radiographic technique, and differences in
      the derivation of a group of "normal" vertebrae. This study suggests that
      reference data of vertebral dimensions should be specific to the technique which
      uses those data as a reference, i.e., MXA.

PMID- 9525348
TI  - Calciotropic hormones and bone markers in the elderly.
AB  - There is a lack of substantial data on changes in calciotropic hormones and bone
      markers in elderly subjects living in North America. Parathyroid hormone (PTH),
      serum 25-hydroxyvitamin D (25(OH)D) and bone markers (serum osteocalcin and urine
      N-telopeptide), were measured in 735 Caucasian subjects (235 men and 500 women)
      aged 65-87 years. There was a significant increase in serum osteocalcin and urine
      N-telopeptide with age in men, and a significant increase in serum osteocalcin
      with age in women. Serum PTH and 25(OH)D showed no significant change with age in
      men or women. After adjusting for age, calcium intake, serum creatinine, season,
      and weight, mean serum PTH (p = 0.01), serum osteocalcin (p = 0.0001) and 24 h
      urine N-telopeptide (p = 0.0001) were higher in women than men, and mean serum
      25(OH)D (p = 0.0001) and 24 h urine calcium (p = 0.0001) were higher in men than
      women. Serum PTH was correlated with serum osteocalcin in men and women, r =
      0.24, r = 0.17, p < 0.001, but not with urine N-telopeptide. Serum PTH was
      inversely correlated with serum 25(OH)D (r = -0.25, r = -034,p < 0.001), and
      positively correlated with serum creatinine (r = 0.14, r = 0.17,p < 0.01) in men
      and women. The prevalence of serum 25(OH)D levels below 12 ng/ml was only 33% in
      females and 0.4% in men. Thus vitamin D deficiency was very uncommon in the
      U.S.A. compared with Europe. Although mean serum PTH was increased in the
      elderly, only 4-6% had PTH levels above the normal range. In summary, the
      increase in serum PTH in the elderly can be explained more by changes in vitamin
      D status than by declining renal function. These data also show significantly
      higher (p = 0.001) bone remodeling markers in women.

PMID- 9525349
TI  - Effect of two training regimens on bone mineral density in healthy perimenopausal
      women: a randomized controlled trial.
AB  - The aim of this randomized controlled trial was to evaluate the effects of 18
      months of calisthenics and endurance training regimens on bone mineral density
      (BMD) in perimenopausal women. Clinically healthy sedentary female volunteers (n
      = 105) aged 52-53 years were randomly assigned to a calisthenics (n = 36),
      endurance (n = 34), or control (n = 35) group. The calisthenics training (2.6
      times per week on average, 50 minutes per session) consisted of rhythmic strength
      endurance exercises by large muscle groups, and the endurance training (3.2 times
      per week, 50 minutes) consisted of walking, stair climbing, ergometer cycling,
      and jogging at a controlled heart rate zone corresponding to 55-75% of the
      individual maximal oxygen uptake (VO2max) of the subjects. The control subjects
      performed a light stretching program once a week The BMD of the lumbar spine (L2
      L4), right femoral neck, calcaneus, and distal radius was measured by dual-energy
      X-ray absorptiometry at 0, 4, 8, 10, 14, and 18 months, and the maximal isometric
      strength during trunk extension and flexion, leg extension, and arm flexion and
      the VO2max by ergospirometry were evaluated at 0, 8, 10, and 18 months of
      intervention. The VO2max improved significantly (p = 0.021) in the endurance
      group. The linear trend of the femoral neck BMD in the endurance group, as
      determined by generalized linear models, was significantly different (p = 0.043)
      from that of the control group, the trend indicating a maintenance of the
      prestudy BMD. In the calisthenics group, the training effect was not significant.
      However, the distal radius BMD of the endurance group showed a significant
      negative trend (p = 0.006). These results suggest that multiexercise endurance
      training maintains the BMD the clinically important femoral neck of
      perimenopausal women. This form of endurance training proved also to be feasible
      for healthy perimenopausal women.

PMID- 9525350
TI  - Bone turnover response to changes in calcium intake is altered in girls and adult
      women in families with histories of osteoporosis.
AB  - Heredity and environmental factors contribute to the development of osteoporosis.
      Because calcium is the major mineral in bone and adolescence is a key period in
      bone acquisition, we hypothesized that bone turnover would be less responsive to
      alterations in dietary calcium intake in both girls and adult women from families
      with histories of osteoporosis. To address this issue, we studied calcium
      kinetics in the maternal grandmother (age range 56-81 years), mother (age range
      32-47 years), and granddaughter (age range 8-15 years) in 10 multigenerational
      families. In five families, the mother and/or grandmother had osteoporosis (bone
      mineral density > or = 2 SD below the age-specific mean). To examine both active
      and passive calcium absorption, families consumed low- (279 +/- 64 mg/day) and
      high- (1580 +/- 385) calcium diets for 10 days prior to administration of oral
      (46Ca) and intravenous (42Ca) stable isotopes. Using repeated measures analysis
      of variance, fractional calcium absorption, true calcium absorption, bone calcium
      deposition, and the balance in bone calcium turnover were all significantly
      affected by diet (p < 0.01). Females from nonosteoporotic families had decreased
      bone calcium resorption with little change in bone calcium deposition during the
      high-calcium study. In contrast, girls and adult women from osteoporotic families
      had increased both bone calcium deposition and resorption during the high-calcium
      period, leading to a less positive balance in bone calcium turnover. A
      significant interaction between bone status and diet was found for bone calcium
      resorption (p < 0.05) and approached significance for bone calcium deposition (p
      < 0.07), effects which were independent of generation. We conclude that girls and
      women from osteoporotic families have a significantly altered bone turnover
      response to acute changes in calcium intake.

PMID- 9525351
TI  - Exercise before puberty may confer residual benefits in bone density in
      adulthood: studies in active prepubertal and retired female gymnasts.
AB  - Exercise during growth may contribute to the prevention of osteoporosis by
      increasing peak bone mineral density (BMD). However, exercise during puberty may
      be associated with primary amenorrhea and low peak BMD, while exercise after
      puberty may be associated with secondary amenorrhea and bone loss. As growth
      before puberty is relatively sex hormone independent, are the prepubertal years
      the time during which exercise results in higher BMD? Are any benefits retained
      in adulthood? We measured areal BMD (g/cm2) by dual-energy X-ray absorptiometry
      in 45 active prepubertal female gymnasts aged 10.4 +/- 0.3 years (mean +/- SEM),
      36 retired female gymnasts aged 25.0 +/- 0.9 years, and 50 controls. The results
      were expressed as a standardized deviation (SD) or Z score adjusted for bone age
      in prepubertal gymnasts and chronological age in retired gymnasts. In the cross
      sectional analyses, areal BMD in the active prepubertal gymnasts was 0.7-1.9 SD
      higher at the weight-bearing sites than the predicted mean in controls (p <
      0.01). The Z scores increased as the duration of training increased (r = 0.32
      0.48, p ranging between <0.04 and <0.002). During 12 months, the increase in
      areal BMD (g/cm2/year) of the total body, spine, and legs in the active
      prepubertal gymnasts was 30-85% greater than in prepubertal controls (all p <
      0.05). In the retired gymnasts, the areal BMD was 0.5-1.5 SD higher than the
      predicted mean in controls at all sites, except the skull (p ranging between
      <0.06 and <0.0001). There was no diminution across the 20 years since retirement
      (mean 8 +/- 1 years), despite the lower frequency and intensity of exercise. The
      prepubertal years are likely to be an opportune time for exercise to increase
      bone density. As residual benefits are maintained into adulthood, exercise before
      puberty may reduce fracture risk after menopause.

PMID- 9525353
TI  - Active resistance to passive smoke.

PMID- 9525352
TI  - Effects of zinc supplementation on vertebral and femoral bone mass in rats on
      strenuous treadmill training exercise.
AB  - The hypothesis that a zinc (Zn) deficit may cause osteopenia in athletes is well
      founded. In rats exposed to strenuous exercise, we evaluated the effect of a zinc
      supplement on femoral and vertebral bone mass determined by dual-energy X-ray
      absorptiometry. Four lots of 93-day-old female Wistar rats were studied. A
      control group of 30 rats were not manipulated (Zn- Ex- group). The experimental
      group of 40 rats was fed a diet supplemented with an additional 20% of Zn/kg of
      feed; this group was divided into two groups of 20 rats each, one that did not
      exercise (Zn+ Ex-) and one that did (Zn+ Ex+). A group of 15 rats exercised but
      did not receive a zinc supplement (Zn- Ex+ group). Training consisted of
      treadmill running for 5 out of 7 days over an 11-week period. Initial speed,
      running time, and treadmill speed were increased gradually. Analysis of variance
      with the Bonferroni/Dunn test showed that the length, weight, bone mineral
      content (BMC), and bone mineral density (BMD) of the femur were less in the Zn-
      Ex+ group than in the others (p < 0.008), and the weight, BMC, and BMD of the
      fifth lumbar vertebra also were lower in the Zn- Ex+ group than in the others (p
      < 0.008). These findings confirm the adverse effects of strenuous exercise
      (treadmill running) on bone tissue in rats and the effectiveness of zinc
      supplementation in preventing it.

PMID- 9525354
TI  - Desirability and problems of early diagnosis of essential thrombocythaemia.

PMID- 9525355
TI  - Abnormal fat accumulation in patients with HIV-1 infection.

PMID- 9525356
TI  - Quorum sensing: potential means of treating gram-negative infections?

PMID- 9525357
TI  - Rubella--could do better.

PMID- 9525359
TI  - Adverse reactions to levodopa: drug toxicity or progression of disease?

PMID- 9525358
TI  - N-methyl-(R)-salsolinol and its relevance to Parkinson's disease.

PMID- 9525360
TI  - WHO's tuberculosis research initiative.

PMID- 9525361
TI  - Impairment of health and quality of life in people with large waist
      circumference.
AB  - BACKGROUND: Symptoms and secondary disorders associated with excess central fat
      distribution are being increasingly recognised. We aimed to define the symptoms
      and assess risks of chronic disorders in people with large waist circumferences.
      METHODS: We did a cross-sectional study of 5887 men and 7018 women aged 20-59
      years from the general population of Maastricht, Amsterdam, and Doetinchem,
      Netherlands. We assessed in health centres respiratory insufficiency, low back
      pain, degree of physical function, presence of non-insulin-dependent diabetes,
      and cardiovascular risk factors. We measured bodyweight, body-mass index, and
      waist circumference by action levels (men: less than action level 1 <94.0 cm,
      action levels 1-2 94.0-101.9 cm, more than action level 2 > or =102.0 cm; women:
      less than action level 1 <80.0 cm, action levels 1-2 80.0-87.9 cm) more than
      action level 2 > or =88.0 cm). The reference group were people with waist
      circumferences lower than action level 1. FINDINGS: All symptoms and risks
      increased among participants higher than action level 2, after adjustment for age
      and lifestyle, by 3.1 (95% CI 2.5-3.7) in men and 2.7 (2.3-3.1) in women for
      shortness of breath when walking upstairs; 4.5 (2.5-7.8) and 3.8 (1.9-7.3) for
      non-insulin-dependent diabetes; and 4.2 (3.6-5.0) and 2.8 (2.4-3.2) for at least
      one major cardiovascular risk factor. Above action level 2, compared with the
      reference group, men and women were at twice the risk of difficulties in everyday
      activities, women were 1.5 times more likely to have low back pain or symptoms of
      intervertebral disc herniation, with secondary problems including hindrance to
      daily activities. INTERPRETATION: People with large waist circumferences have
      excess burden of ill health. Waist action levels could be useful for health
      promotion to raise awareness of the need for weight management.

PMID- 9525362
TI  - Long-term postoperative cognitive dysfunction in the elderly ISPOCD1 study.
      ISPOCD investigators. International Study of Post-Operative Cognitive
      Dysfunction.
AB  - BACKGROUND: Long-term postoperative cognitive dysfunction may occur in the
      elderly. Age may be a risk factor and hypoxaemia and arterial hypotension
      causative factors. We investigated these hypotheses in an international
      multicentre study. METHODS: 1218 patients aged at least 60 years completed
      neuropsychological tests before and 1 week and 3 months after major non-cardiac
      surgery. We measured oxygen saturation by continuous pulse oximetry before
      surgery and throughout the day of and the first 3 nights after surgery. We
      recorded blood pressure every 3 min by oscillometry during the operation and
      every 15-30 min for the rest of that day and night. We identified postoperative
      cognitive dysfunction with neuropsychological tests compared with controls
      recruited from the UK (n=176) and the same countries as study centres (n=145).
      FINDINGS: Postoperative cognitive dysfunction was present in 266 (25.8% [95% CI
      23.1-28.5]) of patients 1 week after surgery and in 94 (9.9% [8.1-12.0]) 3 months
      after surgery, compared with 3.4% and 2.8%, respectively, of UK controls
      (p<0.0001 and p=0.0037, respectively). Increasing age and duration of
      anaesthesia, little education, a second operation, postoperative infections, and
      respiratory complications were risk factors for early postoperative cognitive
      dysfunction, but only age was a risk factor for late postoperative cognitive
      dysfunction. Hypoxaemia and hypotension were not significant risk factors at any
      time. INTERPRETATION: Our findings have implications for studies of the causes of
      cognitive decline and, in clinical practice, for the information given to
      patients before surgery.

PMID- 9525363
TI  - Increasing prevalence of hay fever and atopy among children in Leipzig, East
      Germany.
AB  - BACKGROUND: Several surveys in children and adults have shown significantly lower
      prevalences of asthma and allergic diseases in eastern Europe than in western
      countries. In the former East Germany tremendous changes towards western
      lifestyle have occurred since unification. The aim of this survey was to
      investigate time trends in the prevalence of asthma and allergic diseases among
      children living in the eastern part of Germany. METHODS: In 1995-96, 2334 (87.5%)
      schoolchildren in Leipzig participated in a cross-sectional study that used the
      same methods as a previous survey done shortly after the fall of communism in
      1991-92. A self-administered questionnaire was distributed to the parents.
      Children underwent cold-air challenge and allergy skinprick tests to six common
      aeroallergens. FINDINGS: The prevalence of hay fever (2.3% [34/1454] vs 5.1%
      [115/2252], p<0.0001) and atopic sensitisation (19.3% [252/1303] vs 26.7%
      [434/1624], p<0.0001) increased significantly between 1991-92 and 1995-96.
      However, there was no significant change in the prevalence of asthma, asthma
      related symptoms, or bronchial hyper-responsiveness. INTERPRETATION: These
      findings suggest important differences in the development of atopic disorders.
      The children were born about 3 years before unification and were therefore
      exposed to western living conditions only after the third birthday. Thus, factors
      operating very early in life may be particularly important for the acquisition of
      childhood asthma, whereas the development of atopic sensitisation and hay fever
      may also be affected by environmental factors occurring beyond infancy.

PMID- 9525365
TI  - Visceral abdominal-fat accumulation associated with use of indinavir.
AB  - BACKGROUND: After the addition of the protease inhibitor indinavir to combination
      drug regimens for HIV-1 infection, some patients have experienced an increase in
      abdominal girth with symptoms of abdominal fullness, distension, or bloating. We
      aimed to find out whether this collection of symptoms was associated with changes
      in abdominal fat and whether such changes were associated with indinavir use.
      METHODS: Abdominal computed tomography was used in ten HIV-1-positive patients
      who had such abdominal symptoms to measure total adipose tissue (TAT) and
      visceral adipose tissue (VAT) at the umbilicus (L4 vertebral level). The VAT:TAT
      ratio in the ten cases was compared with that in ten HIV-1-infected patients who
      had been using indinavir without abdominal symptoms for at least 6 months and ten
      HIV-1-infected patients who were not using indinavir. FINDINGS: The mean VAT:TAT
      ratios for the three groups-non-users, symptom-free indinavir users, and
      symptomatic indinavir users-were 0.40 (SD 0.15), 0.59 (0.18), and 0.70 (0.20),
      respectively (p=0.004). The VAT:TAT ratio correlated with duration of indinavir
      use (r=0.47, p=0.01). The mean areas of VAT for the three groups were 106 cm2 (SD
      72), 141 cm2 (65) and 202 cm2 (93), respectively (p=0.03). The mean body-mass
      index of the groups was similar, and patients in the two indinavir groups did not
      gain a significant amount of weight after starting the drug. Serum triglyceride
      values increased after starting indinavir and correlated with VAT:TAT ratios.
      INTERPRETATION: Our data suggest that some HIV-1-infected patients on indinavir
      treatment accumulate intra-abdominal fat that may cause abdominal symptoms.
      Recent evidence suggests that other HIV-1 protease inhibitors may be associated
      with changes in body-fat distribution. Larger studies of protease-inhibitor
      treatment are needed to investigate this association further and to investigate
      metabolic or endocrine mechanisms that may underlie this phenomenon.

PMID- 9525364
TI  - "Buffalo hump" in men with HIV-1 infection.
AB  - BACKGROUND: Enlargement of the dorsocervical fat pad ("buffalo hump") has been
      reported in numerous HIV-1-infected patients. Some investigators have speculated
      that this finding is associated with protease-inhibitor treatment. METHODS:
      Between June, 1995, and October, 1997, we studied eight HIV-1-infected men who
      had developed a buffalo hump while otherwise stable on antiretroviral therapy.
      Measurement of 24 h urinary free cortisol excretion and an overnight low-dose
      dexamethasone suppression test were done to screen for Cushing's syndrome. In one
      patient, plasma cortisol concentrations were measured every 4 h for 24 h to
      assess the circadian rhythm of cortisol. Results of total and regional body
      composition analysis by dual-energy X-ray absorptiometry, and glucose,
      cholesterol, triglyceride, and cortisol concentrations were compared with those
      obtained in a control population of 15 HIV-1-positive men whose age, body-mass
      index (BMI), and CD4-lymphocyte count were within the range of values in the
      eight study patients. FINDINGS: The eight patients with a buffalo hump were
      clinically stable on various antiretroviral regimens, four of which included a
      protease inhibitor. No other signs of Cushing's syndrome were observed, and
      plasma cortisol values did not differ significantly from those of controls. 24 h
      urinary free cortisol excretion was normal in seven patients and slightly raised
      in one (248 nmoles). In this patient, a repeat 24 h urinary free cortisol was 175
      nmoles and plasma cortisol concentrations over 24 h showed a normal circadian
      pattern (nadir 83 nmol/L at 2400 h). All eight patients had normal suppression of
      cortisol values after dexamethasone 1 mg (plasma cortisol less than 83 nmol/L).
      When compared with HIV-1-positive controls, men with a buffalo hump had a
      significantly greater proportion of fat in the trunk region, suggesting central
      fat accumulation. Triglyceride but not cholesterol values were higher in the
      patients than in controls but this difference was not significant. Fasting
      glucose values did not differ significantly. INTERPRETATION: The development of a
      buffalo hump cannot be attributed to hypercortisolism in these eight men.
      Furthermore, its occurrence is not unique to patients on protease inhibitors.
      Although the mechanism for dorsocervical fat accumulation is unclear, we
      speculate that regional abnormalities in lipogenesis and lipolysis occur,
      possibly influenced by the hormonal and metabolic changes seen with HIV-1
      infection and its treatment.

PMID- 9525366
TI  - An eye for horticulture.

PMID- 9525367
TI  - Deafness due to Pro250Arg mutation of FGFR3.

PMID- 9525368
TI  - Cyclooxygenase-2 expression in human monocytes stimulated by meconium.

PMID- 9525369
TI  - Leptin in human plasma is derived in part from the brain, and cleared by the
      kidneys.

PMID- 9525370
TI  - Left atrial reduction: the forgotten Batista.

PMID- 9525371
TI  - Recurrent peritonitis in a patient on dialysis and prophylactic vancomycin.

PMID- 9525372
TI  - K variant of butyrycholinesterase and late-onset Alzheimer's disease.

PMID- 9525373
TI  - Preserved acetylcholinesterase activity in aged cerebral cortex.

PMID- 9525374
TI  - Anti-apoptosis gene, survivin, and prognosis of neuroblastoma.

PMID- 9525376
TI  - Polyglutamine-containing aggregates in neuronal intranuclear inclusion disease.

PMID- 9525375
TI  - High adult mortality in Lusaka.

PMID- 9525377
TI  - UK misconduct case raises informed-consent issues.

PMID- 9525378
TI  - Emerging infectious diseases attract expert attention.

PMID- 9525379
TI  - Can eradicating H pylori prevent gastric cancer?

PMID- 9525380
TI  - The stubborn enigma of obesity.

PMID- 9525381
TI  - Tobacco corporations step up invasion of developing countries.

PMID- 9525382
TI  - China plans to change policy on one-child limit to families.

PMID- 9525383
TI  - US President's Commission ends in discord.

PMID- 9525384
TI  - Frenzy mounts in Italy over assessment of the di Bella regimen.

PMID- 9525385
TI  - Abortion bills introduced to Western Australian parliament.

PMID- 9525386
TI  - Extent of Ireland's crisis pregnancies revealed.

PMID- 9525387
TI  - Intravascular-catheter-related infections.

PMID- 9525388
TI  - Shaping the future of global health cooperation: where can we go from here?
AB  - A review of recent studies and initiatives on global health cooperation groups
      their findings into ten key reform issues. In addressing these issues, policy
      makers need to improve their understanding of what is meant by the shift from
      international to global health. Attention must also be paid to the fundamental
      question of what we want from a system of global health cooperation. Three main
      views currently exist on what priority activities such a system should pursue
      traditionalist, essentialist, and social justice. Reconciliation of these views
      can then be followed by consideration of the structural features of a global
      health organisation for the 21st century. Achievement of the above will require a
      reform process that is more broadly participatory, well-informed, and coherent in
      purpose and direction.

PMID- 9525389
TI  - Obesity is a disease: food for thought.

PMID- 9525390
TI  - Autism, inflammatory bowel disease, and MMR vaccine.

PMID- 9525391
TI  - Autism, inflammatory bowel disease, and MMR vaccine.

PMID- 9525392
TI  - Autism, inflammatory bowel disease, and MMR vaccine.

PMID- 9525393
TI  - Autism, inflammatory bowel disease, and MMR vaccine.

PMID- 9525394
TI  - Autism, inflammatory bowel disease, and MMR vaccine.

PMID- 9525396
TI  - Autism, inflammatory bowel disease, and MMR vaccine.

PMID- 9525395
TI  - Autism, inflammatory bowel disease, and MMR vaccine.

PMID- 9525397
TI  - Twinning, cancer, and genetics.

PMID- 9525398
TI  - Twinning, cancer, and genetics.

PMID- 9525399
TI  - Twinning, cancer, and genetics.

PMID- 9525400
TI  - Somatostatin for acute oesophageal variceal bleeding.

PMID- 9525401
TI  - Autism.

PMID- 9525402
TI  - Magnetic-resonance pelvimetry in breech presentation.

PMID- 9525403
TI  - Magnetic-resonance pelvimetry in breech presentation.

PMID- 9525404
TI  - Understanding human parturition.

PMID- 9525405
TI  - Kangaroo mother care.

PMID- 9525406
TI  - Rembrandt's self-portrait.

PMID- 9525407
TI  - Rembrandt's self-portrait.

PMID- 9525408
TI  - Rembrandt's self-portrait.

PMID- 9525409
TI  - The yield of meta-analysis.

PMID- 9525410
TI  - Genetic associations.

PMID- 9525411
TI  - The pleasures of pipe smoking.

PMID- 9525412
TI  - No cure for the 'flu.

PMID- 9525413
TI  - Finding on-line resources.

PMID- 9525414
TI  - An estimation of the genetically significant dose from diagnostic radiology for
      the South African population, 1990-1991.
AB  - The genetically significant dose was initially defined by UNSCEAR in 1958. The
      National Radiological Protection Board (NRPB) derived a formula from this
      definition as shown in the NRPB Report, NRPB-R106. It combines the frequency of
      radiological examinations obtained during the country-wide survey and estimates
      of gonadal doses for different examination types, together with population and
      child expectancy data. The task was set to find a model in order to draw the best
      representative sample of the population, and it was determined in a unique way,
      namely the so-called Dollar Unit Sampling method. A sample of 27 institutions out
      of a possible 292 (9%) was drawn. The GSD for the total South African population
      was calculated, using the above-mentioned formula, as 95 microGy. The breakdown
      of the genetically significant dose for the various South African race groups was
      Asian--229 microGy; black--67 microGy; people of color (mixed race)--112 microGy;
      and white--463 microGy.

PMID- 9525415
TI  - Simultaneous comparison of the personal UV exposure of two human groups at
      different altitudes.
AB  - A simultaneous comparison of human exposure to solar ultraviolet radiation at two
      locations was performed to study the effect of environmental factors and human
      attitudes on personal ultraviolet exposure. The study took place on 29 October
      1996 in Toowoomba (27.5 degrees S, 151.9 degrees E) and Brisbane (27.4 degrees S,
      153.1 degrees E), Queensland, Australia. From the data collected by calibrated
      ambient ultraviolet monitoring stations located in Toowoomba and Brisbane,
      Toowoomba received 68% more UVA (320-400 nm) and 61% more UVB (280-320 nm) than
      Brisbane from 07:00 to 10:00 Australian Eastern Standard Time (EST). From 10:00
      to 17:00 EST Toowoomba received 5% more UVA and 20% less UVB than Brisbane. High
      ambient ultraviolet levels recorded by ultraviolet stations were reinforced by
      measurement of the personal ultraviolet exposure of human subjects wearing
      polysulfone dosimeters. Contrary to the common belief that the ultraviolet
      exposure to the human body is higher near the beach (i.e., coastal areas) than
      the inland area, the average erythemal weighted ultraviolet exposure on the chest
      and shoulder of each subject in the inland city of Toowoomba (127 km to the west
      of Brisbane) was 30% higher than in the coastal city of Brisbane from 07:00 to
      17:00 EST. Evidence is also presented to suggest a relationship between altitude,
      climatic conditions, the human attitude, and the level of personal exposure to
      ultraviolet radiation.

PMID- 9525416
TI  - Radioactive sealed source accountability--a risk-based approach.
AB  - This paper provides a risk-based approach for establishing threshold
      accountability values for radioactive sealed sources based on current scientific
      information and realistic assumptions. Although this paper focuses specifically
      on accountability thresholds, the methodology provided can be easily modified to
      determine risk-based exemption and licensing thresholds.

PMID- 9525417
TI  - Thorotrast distribution in monkey bone marrow at early and late times after
      injection.
AB  - Thorotrast, a 25% colloidal suspension of 232ThO2, was formerly used as a
      radiographic contrast medium. Although epidemiological studies have shown that
      alpha particles emitted from 232Th and its decay products incorporated in the
      bone marrow cause leukemia, the use of these data for alpha particle induced
      leukemogenesis risk estimation has been criticized mainly for inhomogeneity of
      Thorotrast distribution. Four monkeys were injected with Thorotrast to
      investigate the degree of inhomogeneity in the thorium content of different bone
      marrow sites and the cellular localization of Thorotrast. Two were injected via
      an artery and two via a vein and sacrificed either at 1 wk or 3 to 4 y after
      injection. Microscopic, solid state autoradiography and back scatter electron
      imaging methods were applied to several bone sites to determine the degree of
      inhomogeneity. Quantification was performed using x-ray fluorescence for
      trabecular bone and bone marrow and neutron activation analysis for compact
      bones. At 1 wk Thorotrast was found to be distributed evenly in the red marrow;
      by 3 and 4 y conglomerates were seen which were restricted to macrophages. The
      monkey was found to be a good model for humans. The choice of injection route did
      not noticeably affect the Thorotrast distribution in bones of the skeletal
      system. Considering the even distribution of Thorotrast within the red bone
      marrow at early times after its injection, the inevitable diffusion of thorium
      progeny from the particles, the mobility of bone marrow macrophages, and the well
      established correction factor of self-absorption within conglomerates, these
      results suggest that data derived from Thorotrast patients are useful for risk
      estimation of alpha particle induced leukemia.

PMID- 9525418
TI  - Organically-bound 3H concentration in rice around atomic energy facilities.
AB  - Rice samples collected around atomic energy facilities in the Tokai area were
      analyzed for organically-bound 3H (OBT). Measurement results were compared with
      those for samples from control areas in Japan and the People's Republic of China.
      OBT concentrations of rice in the Tokai area were found to be 4 times higher than
      the control area as maximum. Although this relatively high 3H concentration shows
      the effect of 3H release from the facilities into the environment, the
      concentration level is comparable with those in the rice sample from a northern
      interior region of China. The OBT concentration of rice sample from the general
      environment in interior China was 4.5 times higher than the control area in
      Japan. The radiation dose from the increasing 3H level is negligible in
      comparison with that from natural radiation.

PMID- 9525419
TI  - Radon measurements and mitigation at a fish hatchery.
AB  - Groundwater radon concentration of 83 Bq L(-1) generated indoor radon levels
      exceeding 3,300 Bq m(-3) at a commercial fish hatchery. Passive and active
      mitigation strategies to reduce the waterborne radon levels included a packed
      column, a waterfall through perforated grates, surface aeration, and bottom
      bubblers. Waterborne concentrations were reduced up to 83% using a combination of
      mitigation procedures, but a comparable reduction in indoor radon concentrations
      was not observed. A diurnal cycle showed that indoor radon levels peaked in early
      afternoon, probably as a result of warmer air being dissolved in the water during
      mitigation. Reduction of indoor radon levels below 148 Bq m(-3) was seldom
      achievable with both water mitigation and direct air ventilation at 23 room air
      changes hourly.

PMID- 9525420
TI  - Time-dependent chemical compositions of 13N and 15O induced in air by the
      operation of a high energy electron accelerator.
AB  - Time-dependent chemical compositions for 13N and 15O induced in the air
      atmosphere of a high energy electron accelerator room have been studied using a
      computer simulation method. A radiation chemistry model was developed to describe
      the chemical reactions of 13N and 15O species with the air molecules and their
      radiolytic products. By assuming several chemical forms of 13N and 15O generated
      by the (gamma, n) reaction, the variations of the concentrations of 13N and 15O
      species were simulated under a radiation field. From the comparison between the
      simulations and experiment in a 100 MeV electron linear accelerator (linac)
      facility, the following conclusions were obtained: (1) Just after the (gamma, n)
      reaction, 25-50% of 13N and 15O are present as atoms (13N, 15O) and/or their ions
      (13N+, 15O+) and the remainder as nitrogen and oxygen molecules (13NN, 15OO)
      and/or their ions (13NN+, 15OO+); (2) Neutralization of 13N+ and 15O+ ions into
      13N and 15O atoms occurs instantaneously and the same is the case with the
      neutralization of 13NN+ and 15OO+ ions to 13NN and 15OO molecules; (3) The
      neutralized 13N and 15O atoms react with the air molecules and the radiolytic
      products to form nitrogen oxide compounds and ozone, while 13NN and 15OO remain
      as these molecules. Factors that control the chemical reactions of 13N and 15O
      are discussed.

PMID- 9525421
TI  - European whole body counter measurement intercomparison.
AB  - In order to test the common quality standards for the performance of measurements
      of internal radioactivity, the European Commission funded a European
      intercomparison of whole body counters, which was organized and carried out by
      the Institut fuer Strahlenhygiene (part of the German Bundesamt fuer
      Strahlenschutz). Forty-four whole body counting facilities from forty-two
      institutions in nineteen countries (the fifteen member states of the European
      Union plus Hungary, the Czech Republic, Switzerland and Norway) took part in this
      intercomparison, which made it the most comprehensive ever carried out in Europe.
      For the study, the 70 kg tissue equivalent St Petersburg phantom was used with
      rods containing 40K, 57Co, 60Co, and 137Cs. The overall results of the whole body
      counter study were rather good.

PMID- 9525422
TI  - Hot particle detection using uncertainties in activity measurements of soil.
AB  - The uncertainty in gamma spectroscopic activity measurements is investigated for
      soil containing hot particles. A radioactivity inhomogeneity uncertainty needs to
      be taken into account, which depends on the density of hot particles in the
      sample geometry, the distribution of their activities, and the specific source
      detector geometry. The maximum activity error due to hot particles in our sampled
      Chernobyl soil with a 137Cs activity of 100 kBq kg(-1) soil was 6% for our source
      detector geometry. The methodology presented might have a practical application
      in nuclear power plants to detect hot particles in a large quantity of dust or
      dirt. The number of hot particles present can be estimated if the activity of all
      particles is assumed to be similar. With this assumption 100 g of the
      investigated soil sample would contain about 500 hot particles with an
      approximate activity of 20 Bq each.

PMID- 9525423
TI  - Assessment of occupational and patient dose from diagnostic and therapeutic
      radiation exposure using thermoluminescent dosimetry.
AB  - Radiation doses of occupational personnel exposed from diagnostic x rays,
      therapeutic installations, and patients were measured using thermoluminescent
      dosimeters. The monthly occupational doses from diagnostic x ray ranged from
      0.1076 mSv to 0.5774 mSv, and those from therapeutic treatment ranged from 0.365
      mSv to 0.657 mSv, which is within the dose limit recommended by ICRP 60. The
      patient organ doses were evaluated and found to range from 0.0615 mSv s(-1) to
      2.8823 mSv s(-1) for gonad, 0.3676 mSv s(-1) to 2.1088 mSv s(-1) for thyroid, and
      0.00972 mSv s(-1) to 4.01 mSv s(-1) for eyes.

PMID- 9525424
TI  - An alternative approach to hot spot identification using in situ gamma
      spectrometry measurements on a grid.
AB  - We describe the application of a computer code developed to analyze data from a
      series of in situ gamma spectrometry measurements on a grid. The code was
      designed to be used as a tool when evaluating compliance with regulations that
      set limits on the size and magnitude of elevated activity areas (also known as
      "hot spots"). It calculates location and magnitude of potential elevated activity
      areas consistent with the data, and for each potential elevated area it generates
      a corresponding distribution of radionuclides in the soil. The algorithm uses a
      maximum entropy deconvolution of the data, followed by further analysis. A test
      case using data from actual field measurements is presented.

PMID- 9525425
TI  - Radium and leukemia: is current dogma valid?
AB  - Current reviews have concluded that internal 226Ra appears not to give rise to
      leukemia in humans, a conclusion based on incidence in U.S. female radium dial
      workers. In fact, leukemias have occurred significantly early in female dial
      workers; males occupationally exposed to radium show an excess of leukemias; and
      the rare erythrocytic leukemias appear in male workers as they do in Thorotrast
      case series. It appears more reasonable that Thorotrast data are suitable for
      projection of leukemogenic risk from radium and plutonium than that no concern
      for leukemogenic risk is warranted.

PMID- 9525426
TI  - Comment on "phantom-derived estimation of effective dose equivalent from x rays
      with and without a lead apron".

PMID- 9525427
TI  - Guidelines for limiting exposure to time-varying electric, magnetic, and
      electromagnetic fields (up to 300 GHz). International Commission on Non-Ionizing
      Radiation Protection.

PMID- 9525428
TI  - Cerebrospinal fluid viral load in HIV-1-infected patients without antiretroviral
      treatment: a longitudinal study.
AB  - HIV-1 RNA and neopterin levels were observed longitudinally for 20 to 68 months
      (mean, 37.5 months) in cerebrospinal fluid (CSF) and serum in 15 HIV-1-infected
      patients not receiving antiretroviral treatment. During the course of infection
      the HIV-1 RNA levels increased significantly in CSF, from a mean of 3.08 to 3.51
      log10 copies RNA/ml (p < .01). A significant positive correlation was found
      between the CSF levels of HIV-I RNA and neopterin (rs = 0.54; p < .001), which
      increased from 13.6 to 19.6 nmol/L (p < .01). No significant changes in HIV-1 RNA
      or neopterin levels were found in serum. We suggest that the increase of CSF
      viral load with time in HIV-1 infection triggers an intrathecal immune activation
      reflected by increased CSF levels of neopterin. These results are in accordance
      with the theory that a chronic immune stimulation within the central nervous
      system (CNS) is involved in the pathogenesis of neurologic HIV-1 disease.

PMID- 9525429
TI  - Marked inhibitory activity of masked aryloxy aminoacyl phosphoramidate
      derivatives of dideoxynucleoside analogues against visna virus infection.
AB  - Lipophilic masked aryloxyaminoacylphosphoramidate derivatives of 2',3'
      dideoxynucleoside (ddN) analogues with potent anti-HIV activity (i.e., stavudine
      [d4T], azidothymidine [AZT], dideoxycytidine [ddC], 3'thio-2',3'-dideoxy cytidine
      [3TC], dideoxyadenosine [ddA], and 2',3'-didehydro-2',3'-dideoxyadenosine [d4A])
      activity were evaluated for their activity against visna virus (VV) in sheep
      choroid plexus (SCP) cells. The activity of several prodrug derivatives against
      VV proved markedly superior to that of the corresponding free ddN analogues. In
      particular, the d4A and ddA prodrug derivatives were exquisitely inhibitory in
      this model system (50% effective concentration [EC50], < or = 0.003 microM), and
      their anti-VV potency exceeded by at least 200-fold the antiviral potency of the
      corresponding free nucleosides. Marked differences were noted in the anti-VV
      potencies of several of the test compounds depending on the nature of the amino
      acid linked to the 5'-phosphate moiety, the nature of the nucleoside, or both. In
      view of the stability of the prodrugs in lamb serum, the VV infection model in
      lambs may be considered highly useful for investigating the in vivo
      antiretroviral efficacy of these type of drugs, particularly the d4T, ddA, and
      d4A prodrug derivatives.

PMID- 9525430
TI  - Unintegrated circular HIV-1 DNA in the peripheral mononuclear cells of HIV-1
      infected subjects: association with high levels of plasma HIV-1 RNA, rapid
      decline in CD4 count, and clinical progression to AIDS.
AB  - We observed 36 HIV-infected patients to evaluate whether the presence of tandem 2
      long terminal repeat circular unintegrated HIV-1 DNA (2-LTR) in peripheral blood
      mononuclear cells (PBMC) at baseline was associated with acceleration of HIV
      disease. Detection of 2-LTR at baseline correlated with high plasma HIV-1 RNA
      levels (p < .01), recovery of culturable HIV-1 from plasma (p = .02), and
      progression to AIDS during follow-up (p = .01). More patients with 2-LTR (68%)
      than without 2-LTR (31%) had a decline in CD4 levels of >50 cells/mm3 over the
      first 18 months of follow-up (p = .04), and the average annual CD4 decline was
      35% in patients with 2-LTR compared with 16% in those without 2-LTR (p = 0.06).
      Detection of 2-LTR in PBMC at baseline was an independent predictor of high
      plasma HIV-1 RNA levels and subsequent CD4 cell decline in this cohort of
      patients with predominantly nonsyncytium-inducing (NSI) isolates at baseline. The
      presence of 2-LTR in PBMC appears to be reflective of ongoing HIV-1 replication,
      as measured by plasma HIV-1 RNA levels, and identifies persons at risk for
      immunologic and clinical decline.

PMID- 9525431
TI  - Virologic, immunologic, and clinical parameters in the incidence and progression
      of anal squamous intraepithelial lesions in HIV-positive and HIV-negative
      homosexual men.
AB  - Anal cancer may be preceded by anal squamous intraepithelial lesions (ASIL), but
      the natural history of ASIL is poorly understood. In this report, we characterize
      the 2-year incidence and progression of low-grade SIL (LSIL) and high-grade SIL
      (HSIL) in a cohort study in 346 HIV-positive and 262 HIV-negative homosexual or
      bisexual men. Subjects were studied at defined intervals using anal cytology,
      anoscopy with biopsy of visible lesions, human papillomavirus (HPV) testing, HIV
      serostatus, CD4 level, and data on medical history and lifestyle. The incidence
      of HSIL within 2 years was 20% in HIV-positive men and 8% in HIV-negative men who
      were normal at baseline. In total, 62% of HIV-positive and 36% of HIV-negative
      men with LSIL at baseline progressed to HSIL. The relative risk (RR) for anal
      disease progression in HIV-positive men was 2.4 (95% confidence interval [CI],
      1.8-3.2) when compared with HIV-negative men. The RR increased to 3.1 (95% CI,
      2.3-4.1) in HIV-positive men with CD4 counts <200/mm3. Infection with multiple
      HPV types was a risk factor for anal disease progression in both HIV-positive (RR
      = 2.0; 95% CI, 1.0-4.1) and HIV-negative (RR = 5.1; 95% CI, 2.3-11) men. The
      incidence of anal HSIL and progression of LSIL to HSIL within 2 years of follow
      up is high in HIV-positive homosexual or bisexual men and to a lesser extent, in
      HIV-negative men. Men with the above risk factors may be at increased risk of
      developing anal cancer.

PMID- 9525433
TI  - Safety study of nonoxynol-9 as a vaginal microbicide: evidence of adverse
      effects.
AB  - Nonoxynol-9 (N-9) is virucidal in vitro, and is therefore a candidate microbicide
      for preventing sexual transmission of HIV. However, the activity of N-9 is
      nonspecific, suggesting that virucidal levels may produce adverse effects
      including epithelial disruption, inflammation of the genital mucosa, or both. A
      randomized placebo controlled trial of daily use of 100 mg of N-9 took place for
      1 week in 40 female volunteers. Outcome measures included symptoms, colposcopic
      and histologic changes in the genital tract, and impact on vaginal flora. Genital
      irritation was reported by 10 of the N-9 and 5 of the placebo group. Colposcopy
      showed erythema in 9 of the N-9 group and 2 of the placebo group. Histologic
      inflammation was found in 7 of the N-9 group and 2 of the placebo group.
      Inflammatory changes were characterized by patchy infiltration of the lamina
      propria predominantly with CD8+ lymphocytes and macrophages, in the absence of
      epithelial disruption. A transient reduction in numbers of lactobacilli was
      observed in 9 of the 15 women using N-9, and 6 of 18 women using placebo. N-9
      used for 7 days in a standard spermicidal dose was associated with increased
      irritation, colposcopic and histologic evidence of inflammation and was more
      frequently associated with reduction in numbers of lactobacilli during gel use.
      The clinical significance of the recruitment of cells susceptible to HIV
      infection to the genital mucosa is unknown but raises concerns about the
      suitability of N-9 as a microbicide when given in this dose.

PMID- 9525434
TI  - Laboratory test differences associated with HTLV-I and HTLV-II infection.
      Retrovirus Epidemiology Donor Study Investigators.
AB  - Reports of laboratory abnormalities associated with HTLV-I and HTLV-II infection
      are inconsistent. We assessed complete blood counts and selected serum chemistry
      measures at enrollment in a cohort of 153 HTLV-I-seropositive, 386 HTLV-II
      seropositive, and 795 HTLV-seronegative blood donors. Linear and logistic
      regression were used to adjust for potential confounding variables including age,
      gender, race/ethnicity, education level, blood center, and injection drug use.
      Compared with seronegative donors, absolute lymphocyte counts were 6% and 10%
      higher, on average, in HTLV-I-infected (p = .03) and HTLV-II-infected (p = .0001)
      donors, respectively. HTLV-I- and HTLV-II-seropositive donors had, on average,
      17,630 (p = .003) and 15,160 (p = .0005) more platelets, respectively. HTLV-I
      infected donors also had an average of 30 fewer eosinophils/microl (p = .003) and
      a slightly higher level of lactic dehydrogenase (p = .05). HTLV-II-infected
      subjects had on average, an 11% decrease in creatine kinase (p = .006), a minor
      increase in mean corpuscular volume (p = .01), and a slightly lower serum calcium
      level (p = .0005). These results indicate that both HTLV-I and HTLV-II may raise
      levels of lymphocytes and platelets by unknown mechanisms. Lower eosinophil
      counts may be related to the increased susceptibility of HTLV-I-infected subjects
      to parasitic diseases.

PMID- 9525435
TI  - Randomized, controlled study of the safety and efficacy of intravenous cidofovir
      for the treatment of relapsing cytomegalovirus retinitis in patients with AIDS.
AB  - To assess the effect of intravenous cidofovir on delaying progression of
      previously treated, relapsing cytomegalovirus (CMV) retinitis, we conducted a
      randomized, controlled comparison of two maintenance dose levels of cidofovir.
      One hundred and fifty patients with AIDS and CMV retinitis that had progressed or
      was persistently active despite treatment with ganciclovir, foscarnet, or both
      were randomized to receive induction cidofovir, 5 mg/kg once weekly for 2 weeks,
      then maintenance therapy with either 5 mg/kg or 3 mg/kg once every other week.
      Concomitant probenecid and intravenous hydration were administered with each
      cidofovir dose. Retinitis progression was assessed in the first 100 patients by
      bilateral, full-field retinal photographs read at a central reading center by an
      ophthalmologist masked to treatment assignment. Incidence of side effects,
      changes in visual acuity, and mortality were also assessed. Median time to
      retinitis progression as assessed by retinal photography was not reached (95%
      confidence interval [CI], 115 days-upper limit not reached) in the 5-mg/kg group,
      and was 49 days (95% CI, 35-52 days) in the 3-mg/kg group (p = .0006). Dose
      dependent asymptomatic proteinuria (39%) and serum creatinine elevation (24%)
      were the most common adverse events thought to be related to cidofovir.
      Reversible probenecid reactions including constitutional symptoms and nausea
      occurred in 65 of 150 (43%) patients. Cidofovir therapy is effective in delaying
      progression of CMV retinitis that had previously progressed using other anti-CMV
      therapies.

PMID- 9525432
TI  - Anal squamous intraepithelial lesions in HIV-positive and HIV-negative homosexual
      and bisexual men: prevalence and risk factors.
AB  - Anal cancer is more commonly found in homosexual and bisexual men than cervical
      cancer is in women. Invasive anal cancer may be preceded by anal squamous
      intraepithelial lesions (ASIL), and treatment of ASIL may prevent the development
      of anal cancer. We characterized the prevalence and risk factors for ASIL in 346
      HIV-positive and 262 HIV-negative homosexual men. Anal cytology, biopsy of
      visible anal lesions, and human papillomavirus (HPV) tests were performed, and
      data on HIV serostatus, CD4 count, and medical and lifestyle history were
      collected. ASIL was diagnosed in 36% of HIV-positive men and 7% of HIV-negative
      men (relative risk [RR] = 5.7; 95% confidence interval [CI], 3.6-8.9). Among HIV
      positive men, the RR for ASIL increased with lower CD4 levels but was elevated
      even in men with CD4 levels >500/mm3 (RR = 3.8; 95% CI, 2.1-6.7) when compared
      with HIV-negative men. High-level HPV infection, as measured by detection of both
      hybrid capture (HC) group A and group B types, was another significant risk
      factor for ASIL in both HIV-positive men (RR = 8.8; 95% CI, 2.3-35) and HIV
      negative men (RR = 20; 95% CI, 5.5-71) when compared with HC-negative men. HIV
      negative men with anal HPV infection and HIV-positive men, regardless of CD4
      level, are at high risk for ASIL.

PMID- 9525437
TI  - Evaluating the cost of medications for ambulatory HIV-infected persons in
      association with landmark changes in antiretroviral therapy.
AB  - Costs of medications for ambulatory HIV-infected people increase as knowledge of
      antiretroviral therapy and therapy for opportunistic infection grows. We
      evaluated the evolution of drug costs for HIV-infected persons who attend a
      university clinic in Baltimore, Maryland. Cross-sectional abstracts of a cohort
      of patients for four periods, corresponding to landmark changes in therapy, who
      attended the clinic between June 1995 and September 1996 were obtained. Monthly
      medication costs for all patients were calculated. Mean costs increased
      significantly (p < .01) from period 1 ($447 U.S.) to period 4 ($1048 U.S.).
      Multivariate analysis only revealed higher costs for patients with a CD4+ count
      <200 cells/mm3 (p < .001). The proportion of costs attributable to antiretroviral
      therapy increased from 34% in period 1 to 53% in period 4. Combination therapy
      increased >10-fold, from 8% in period 1 to 94% in period 4. Protease inhibitor
      use also increased significantly, from 4% in period 2 to 53% in period 4. We
      quantified the increase in costs of medications from mid-1995 to late 1996.
      Increases in costs appear to be the result of increasing complexity of drug
      regimens, particularly antiretroviral therapy in combinations.

PMID- 9525436
TI  - Size and duration of zidovudine benefit in 1003 HIV-infected patients: U.S. Army,
      Navy, and Air Force natural history data. Military Medical Consortium for Applied
      Retroviral Research.
AB  - OBJECTIVES: The study's objectives were to determine the size and duration of
      benefits of early versus delayed versus late treatment with zidovudine (ZDV) on
      disease progression and mortality in HIV-infected patients, and whether patients
      rapidly progressing before ZDV treatment had a different outcome from those not
      rapidly progressing before ZDV. DESIGN: The design was an inception cohort of
      1003 HIV-infected patients. One hundred and seventy-four of the 1003 patients
      were treated before CD4 counts fell to <400 x 10(9)/L, ("early treatment"); 183
      of 1003 patients were treated after CD4 counts fell to <400 x 10(9)/L but before
      clinical disease developed ("delayed treatment"); and 646 of the 1003 patients
      had either been treated after clinical disease developed or had not been treated
      at all by the end of follow-up ("late treatment"). Outcomes were progression to
      clinical HIV disease and mortality. RESULTS: The relative risk (RR) of
      progression for early versus delayed treatment was 0.58 (p < .03), and durability
      of ZDV benefits on progression was estimated at no more than 2.0 years; however,
      this estimate had wide confidence intervals. The RR of progression for delayed
      versus late treatment was 0.54 p < .0001, and durability of ZDV benefits was
      estimated at 1.74 years; this estimate had narrow confidence intervals. Survival
      was better for the early versus delayed treatment (RR = 0.55), but this
      difference was not statistically significant. In the subgroup of patients with
      more rapid CD4 decline prior to ZDV therapy, significant benefits on progression
      were observed for early versus delayed ZDV therapy (RR = 0.42, p = .02) and
      delayed versus late ZDV therapy (RR = 0.51; p = .0004). Duration of benefit was
      estimated to be 4.5 years (early versus delayed) and 1.7 years (delayed versus
      late). For patients with less rapid pre-ZDV decline in CD4 levels, a significant
      progression benefit was observed for delayed versus late therapy (RR = 0.50; p =
      .02). Duration of benefit in this subgroup was estimated to be 1.8 years. No
      significant benefit was found for early versus delayed treatment (RR = 1.12) in
      the less rapid pre-ZDV CD4 cell decline subgroup. CONCLUSIONS: Early treatment
      compared with delayed treatment was associated with a sizable reduction in HIV
      progression, but the duration of benefits was estimated to last only about 2
      years. Delayed treatment compared with late treatment with ZDV was associated
      with substantial reduction of progression, but this reduction was also clearly
      limited in duration. Benefits on progression and mortality for the early
      treatment group were heavily dependent on the pre-ZDV CD4 slope. In the subgroup
      of patients with the most rapid pre-ZDV CD4 cell declines, the duration of
      benefit was much longer, possibly as long as 4 years.

PMID- 9525438
TI  - Unsafe sex in men who have sex with both men and women.
AB  - The sexual behaviors of bisexually active men, defined as men having sex with a
      man and a woman in previous 6 months, were compared with men who had sex with men
      only. Differential sexual practices associated with HIV risk between the two
      groups of men, as well as in the bisexual men with their male and female
      partners, were evaluated. Cross-sectional analyses were performed on baseline
      data from a prospective cohort of 508 young gay men recruited from bars, college
      campuses, and a health center in Boston from 1993 to 1994. Odds ratios (OR) and
      95% confidence intervals (CI) were calculated on categorical variables, and
      McNemar's chi2 was used to compare the behaviors of bisexual men with their male
      versus female sex partners. Six months before the interview, 47 (10%) men had
      male and female sex partners, and 383 men had only male sex partners during the
      past year or ever. Fifty-eight percent of the men in the study had a female
      sexual partner in their lifetime, and 18% during the past year. Bisexual men were
      more likely to have drinking problems as identified by the Michigan Alcoholism
      Screening Test (MAST; OR = 3.96, 95% CI = 1.54-10.20), and fewer male partners
      over their lifetime (mean +/- standard deviation [SD], 24+/-42; median, 7; versus
      mean +/- SD, 69+/-516; median, 12), although this difference was not
      statistically significant. The two groups had similar levels of unprotected anal
      intercourse (25.5% versus 29.5%); however, bisexual men were half as likely to
      have anal sex as homosexual men (OR = 0.50; 95% CI = 0.27-0.93). Bisexual men
      were three times as likely to have unprotected sex with their female partner as
      their male partner (OR = 3.0; 95% CI = 1.02-8.8). Stratified analysis revealed
      similar discordant behavior while sober (OR = 4.0), drinking (OR = 7.0), and
      while drinking with concurrent drug use (OR = 8.0). Among this cohort of men who
      have sex with men (MSM), a sizable proportion also had vaginal sex with female
      partners in the previous 6 months. Bisexually active men were more likely to have
      unprotected sex with their female partners compared with their male partners,
      potentially increasing the risk for HIV and other sexually transmitted diseases.
      Behavioral interventions directed toward MSM need to address bisexual behaviors.

PMID- 9525439
TI  - The social context of drinking, drug use, and unsafe sex in the Boston Young Men
      Study.
AB  - The objective of this study was to evaluate the relation between drinking, drug
      use, and unprotected anal intercourse in young men who have sex with men. A cross
      sectional analysis of first-visit data from a prospective cohort of 508 young gay
      men recruited from 1993 through 1994 from bars, college campuses, and the Fenway
      Community Health Center in Boston was performed. The major outcome measures were
      any unprotected anal intercourse, after drinking and when sober, stratified by
      type of sexual partner (steady or nonsteady) during the previous 6 months and
      during the most recent sexual encounter. The average age of the cohort was 23.3
      years; 77.6% were white, and 76.4% were in college. These young men had a median
      of 10.5 male sexual partners in their lifetimes, and 3 sexual partners in the
      previous 6 months before enrollment. One hundred and thirty-four (26%) reported
      unprotected anal intercourse during the previous 6 months. Individuals who had
      unprotected anal intercourse were more likely to have a drinking problem (odds
      ratio [OR] = 1.95; 95% confidence interval [CI] = 1.26-3.01) and drank more (20.4
      ml/day versus 13.9 ml/day; p < or = 0.01), compared with individuals who did not
      engage in unprotected anal intercourse. Overall, men were significantly less
      likely to have unprotected anal intercourse after alcohol or drug use, based on a
      series of paired analysis (OR = 0.27; 95% CI = 0.15-0.48). However, when we
      stratified by type of sexual partner, men were significantly more likely to have
      unprotected anal intercourse with their nonsteady sexual partners after drinking
      than when sober (OR = 4.33; 95% CI = 1.37-13.7), but were significantly less
      likely to have unprotected anal intercourse with steady partners (OR = 0.27; 95%
      CI = 0.15-0.48). The patterns observed as already mentioned for drinking were
      also found for substance use in general. Men who were more likely to have
      unprotected anal intercourse after substance use were significantly more likely
      to have a drinking problem (OR = 7.65; 95% CI = 2.34-24.59). These results
      suggest that the role of alcohol and unsafe sex in young gay men is complex, with
      the role of situational factors of paramount importance. Alcohol and substance
      use interventions designed to reduce HIV risk need to specify the role of
      substance use in the sexual context to be successful.

PMID- 9525440
TI  - Interpretation of indeterminate HIV serology results in an incarcerated
      population.
AB  - The objective of this study was to evaluate the significance of indeterminate HIV
      test results in the prison setting. No specific information or guidelines are
      currently available to direct counseling of incarcerated persons with an
      indeterminate HIV test. A medical chart review was conducted on all incarcerated
      inmates at the Rhode Island State Prison who received indeterminate HIV test
      results between the inception of mandatory testing in 1990 and October 1996.
      Thirty-five inmates had an indeterminate HIV Western blot (WB) result, and 31 had
      follow-up HIV testing. Twenty-three of 31 (74%) of the prisoners with follow-up
      HIV tests seroconverted (95% confidence interval, 55%-88%). Drug/alcohol use,
      including crack cocaine and injection drug use, was strongly associated with
      seroconversion (p < 0.01, odds ratio [OR] = 11.8, relative risk [RR] = 2.04).
      Injection drug use was also significantly associated with seroconversion (p =
      0.03, OR = 9.3, RR = 1.56). This is the highest rate of seroconversion ever
      reported for persons with indeterminate WB test results. Indeterminate test
      results need to be interpreted differently in the prison setting than in the
      community. Prison inmates with indeterminate HIV serology should be counseled
      that in all likelihood they are HIV-infected, and confirmatory viral load testing
      should be conducted immediately.

PMID- 9525441
TI  - Prevalence of HTLV-I in leprosy patients in two sanatoriums in Japan.
AB  - To determine the association between leprosy and HTLV-I, 450 and 394 leprosy
      patients in two sanatoriums in Japan (Sanatorium-A in Okayama prefecture and
      Sanatorium-B in Gunma prefecture) were investigated serologically for antibodies
      to HTLV-I. Serology was positive for HTLV-I in 38 (8.4%) of 450 leprosy patients
      in Sanatorium-A and in 34 (8.6%) of 394 patients in Sanatorium-B. Prevalence was
      much higher than that in the general population of these areas in Japan. A large
      proportion of HTLV-I-positive patients in both sanatoriums came from HTLV-I
      nonendemic areas in Japan, suggesting that HTLV-I infection occurred after the
      patients arrived at the sanatoriums. Infection through sexual contact or reuse of
      needles for frequent vaccination are possible routes of infection for HTLV-I in
      these cases.

PMID- 9525442
TI  - IL-10: evolving concepts.

PMID- 9525443
TI  - Discontinuing venom immunotherapy: extended observations.
AB  - BACKGROUND: Our studies of discontinuing venom immunotherapy after at least 5
      years have led to the conclusion that the residual risk of a systemic reaction to
      a sting was in the range of 5% to 10% in adults, and no severe or life
      threatening reaction occurred with 270 challenge stings in 74 patients after 1 to
      5 years without venom immunotherapy. OBJECTIVE: The objective of this study was
      to extend our observation of patients who discontinue venom immunotherapy over 5
      to 10 years and to determine which patients are at higher risk for a reaction.
      METHODS: Patients who discontinued venom immunotherapy were surveyed for 3
      consecutive years to determine the frequency of systemic reactions to field
      stings and the fate of venom sensitivity. The evaluation included the 74 patients
      previously studied (group 1) and 51 additional patients followed after stopping
      therapy in our clinical center (group 2). RESULTS: Of the original 74 patients,
      11 had field stings again after 3 to 7 years without venom immunotherapy, with
      one systemic reaction (dyspnea). Of the 51 patients in the other group, 15 were
      stung, of whom four (26%) had systemic reactions, including respiratory symptoms
      requiring epinephrine. Review of group 1 and group 2 revealed that half of the
      patients who had systemic reactions to a sting after stopping venom immunotherapy
      had a history of a systemic reaction occurring during venom immunotherapy (to an
      injection or a sting). Systemic reactions occurred in three patients who had
      negative skin test reactions; all three had very low but detectable venom
      specific serum IgE antibody levels as determined by RAST and had a history of
      systemic reactions during venom immunotherapy. Greater severity of the
      pretreatment reaction was not associated with higher frequency of reaction to
      stings after stopping therapy but was associated with greater severity if a
      reaction did occur. CONCLUSIONS: Venom immunotherapy (yellow jacket/mixed vespid)
      in adults can be discontinued after 5 to 6 years with a 5% to 10% residual risk
      of a systemic reaction. Risk factors may include history of a systemic reaction
      during venom immunotherapy, persistent strongly positive skin test sensitivity,
      and the severity of the pretreatment reaction.

PMID- 9525445
TI  - Effects of budesonide by means of the Turbuhaler on the hypothalmic-pituitary
      adrenal axis in asthmatic subjects: a dose-response study.
AB  - BACKGROUND: As a general phenomenon, corticosteroids may suppress the activity in
      the hypothalamic-pituitary-adrenal (HPA) axis. The adrenal stimulation test is a
      commonly used method to assess the relative risk of exogenous corticosteroids to
      induce systemic side effects. OBJECTIVES: This clinical trial was performed to
      assess the effects of budesonide on the HPA axis (at 800, 1600, or 3200
      microg/day, given as a twice daily regimen, administered by means of the
      Turbuhaler) in adult patients with mild, non-steroid-dependent asthma. METHODS:
      Sixty-four asthmatic patients received budesonide or placebo by inhalation or 10
      mg/day oral prednisone once daily as a positive control in a double-blind, double
      dummy, randomized, placebo-controlled, parallel-group, multicenter study. Plasma
      cortisol concentration was measured to assess the effect on the HPA axis before
      and during a 6-hour infusion of synthetic adrenocorticotropic hormone (ACTH),
      cosyntropin. RESULTS: After 6 weeks of treatment, plasma cortisol concentrations
      after adrenal stimulation by cosyntropin infusion had fallen by 4% in the placebo
      group; by 13%, 11%, and 27% in the budesonide groups (800, 1600, and 3200
      microg/day, respectively); and by 35% in the prednisone group. The decrease was
      significant only in the 3200 microg/day budesonide (p = 0.03) and prednisone (p =
      0.005) groups. Over the same time period, decreases in basal plasma cortisol
      concentrations were 1% in the placebo group; 19%, 19%, and 34% in the three
      budesonide groups; and 37% in the prednisone group. Only in the prednisone group
      was the decrease significant (p = 0.03 vs placebo). CONCLUSIONS: In this study
      budesonide inhaled by means of the Turbuhaler, at doses recommended for clinical
      use (800 or 1600 microg/day), did not produce any statistically significant
      suppression of the HPA axis compared with placebo.

PMID- 9525444
TI  - Fexofenadine's effects, alone and with alcohol, on actual driving and psychomotor
      performance.
AB  - BACKGROUND: Fexofenadine is the hydrochloride salt of terfenadine's active
      metabolite. OBJECTIVE: Fexofenadine's effects on performance were assessed in
      this study for the purpose of determining its safety of use by patients who
      engage in potentially dangerous activities, especially car driving. METHODS:
      Fexofenadine was administered in daily doses of 120 or 240 mg, each in single and
      divided units given over 5 days. Two milligrams of clemastine given twice daily
      and placebo were given in similar series. Twenty-four healthy volunteers (12 men,
      12 women; age range, 21 to 45 years) participated in a double-blind six-way
      crossover study. Psychomotor tests (critical tracking, choice reaction time, and
      sustained attention) and a standardized actual driving test were undertaken
      between 1.5 to 4 hours after administration of the morning dose on days 1, 4, and
      5 of each series. On day 5, subjects were challenged with a moderate alcohol dose
      before testing. RESULTS: Fexofenadine did not impair driving performance. On the
      contrary, driving performance was consistently better during twice daily
      treatment with 120 mg fexofenadine than during treatment with placebo,
      significantly so on day 4. Both of the 240 mg/day regimens significantly
      attenuated alcohol's adverse effect on driving on day 5. Effects in psychomotor
      tests were not significant, with the exception of the critical tracking test in
      which the first single doses of fexofenadine, 120 and 240 mg, had significantly
      impairing effects. CONCLUSION: It was concluded that fexofenadine has no effect
      on performance after being taken in the recommended dosage of 60 mg twice daily.

PMID- 9525447
TI  - Environmental and clinical study of latex allergy in a textile factory.

PMID- 9525446
TI  - Chronic cough resembles asthma with IL-5 and granulocyte-macrophage colony
      stimulating factor gene expression in bronchoalveolar cells.
AB  - BACKGROUND: Chronic cough is a multifactorial condition, which, like asthma, can
      be associated with eosinophilic airway inflammation. In asthma, airway
      eosinophilia is believed to be mediated by cytokines such as interleukin-5 and
      granulocyte-macrophage colony stimulating factor (GM-CSF). The role of these
      cytokines in chronic cough is unclear. OBJECTIVE: The aim of this study was to
      examine gene expression for IL-5 and GM-CSF in chronic cough and compare the
      results with those found in asthma. METHODS: We studied adults with asthma (n =
      12), chronic cough responsive to inhaled corticosteroid (ICS-responsive cough) (n
      = 9), and chronic cough not responsive to inhaled corticosteroid (non-ICS
      responsive cough) (n = 4). Bronchoalveolar lavage (BAL) was performed, and
      cytokine gene expression was assessed by using a semiquantitative reverse
      transcriptase polymerase chain reaction. RESULTS: IL-5 mRNA was expressed by BAL
      cells from nine of 12 asthmatic subjects and six of nine subjects with ICS
      responsive chronic cough. IL-5 mRNA was not detected in subjects with non-ICS
      responsive chronic cough (zero of four subjects, p < 0.05). GM-CSF mRNA was
      expressed in BAL cells from seven of 12 asthmatic subjects and six of nine
      subjects with ICS-responsive cough. GM-CSF mRNA was not detected in non-ICS
      responsive cough subjects (zero of four subjects, p < 0.05). GM-CSF gene
      expression was related to the degree of methacholine airway responsiveness in
      asthmatic subjects (r = -0.59). CONCLUSION: We conclude that chronic cough, like
      asthma, is associated with airway inflammation and gene expression for IL-5 and
      GM-CSF. Ongoing expression of these cytokines is likely to be related to the
      persistence of airway inflammation and chronic cough.

PMID- 9525449
TI  - Beta2-adrenoceptor regulation and bronchodilator sensitivity after regular
      treatment with formoterol in subjects with stable asthma.
AB  - OBJECTIVE: We have previously found that beta2-adrenoceptor downregulation and
      bronchodilator desensitization to albuterol occurred at 36 hours after stopping
      regular treatment with twice daily salmeterol. In this study we have evaluated
      these same effects with formoterol given once or twice daily on a regular basis.
      METHODS: In a randomized, placebo-controlled, double-blind, double-dummy
      crossover study, 16 subjects with mild-to-moderate stable asthma (mean [SD] age,
      32.5 [15.3] years; mean [SD] FEV1, 73.2 [12.1] percent predicted) receiving
      regular inhaled corticosteroid therapy received 1 week of treatment with
      formoterol dry powder (24 microg twice daily [8 AM/8 PM]), formoterol (24 microg
      once daily [8 PM]), or identical placebo. Lymphocyte beta2-adrenoceptor
      parameters and a dose-response curve to inhaled albuterol (200 to 1600 microg)
      were evaluated at 36 hours after the last dose of each treatment period. RESULTS:
      There were no significant differences in the mean values for albuterol dose
      response effects among the three treatment regimens. Comparison of maximal
      bronchodilator responses between treatments (mean and SEM as change from
      baseline) revealed no significant differences between treatments for FEV1 (0.47 L
      [0.06 L] for placebo vs 0.48 L [0.07 L] for 24 microg once daily formoterol vs
      0.51 L [0.08 L] for 24 microg twice daily formoterol) or for forced expiratory
      flow, mid-expiratory phase (FEF25-75) (0.80 L/sec [0.12 L/sec] for placebo vs
      0.80 L/sec [0.16 L/sec] for 24 microg once daily formoterol vs 0.89 L/sec [0.14
      L/sec] for 24 microg twice daily formoterol). Formoterol also had no significant
      effect on mean lymphocyte beta2-adrenoceptor density. However, in five of seven
      patients with the homozygous Gly-16 polymorphism, beta2-adrenoceptor density was
      downregulated by twice daily formoterol, whereas only two such cases exhibited a
      reduction in maximal FEV1 response to albuterol. CONCLUSIONS: The results of this
      study showed that for patients taking inhaled corticosteroids, overall beta2
      adrenoceptor regulation and associated bronchodilator sensitivity to inhaled
      albuterol were unaltered at 36 hours after stopping regular treatment with
      formoterol. However, in a subset of patients who were Gly-16 homozygous, there
      was a tendency towards downregulation but not desensitization. Further studies in
      subjects with more severe asthma are required to assess the clinical relevance of
      these findings.

PMID- 9525448
TI  - Expression of IL-4, Cepsilon RNA, and Iepsilon RNA in the nasal mucosa of
      patients with seasonal rhinitis: effect of topical corticosteroids.
AB  - BACKGROUND: Nasal allergen provocation has demonstrated that allergen-induced
      rhinitis is associated with an increase in local IL-4 mRNA and IgE heavy chain
      (Cepsilon) and IgE heavy chain promoter (Iepsilon) RNA and that pretreatment with
      topical glucocorticosteroids inhibits the increase in these transcripts.
      OBJECTIVE: This study was undertaken to determine whether observations made after
      acute allergen provocation can be extended to the case of chronic exposure
      experienced during the pollen season. METHODS: Biopsy specimens were obtained
      from the inferior turbinate of 33 pollen-sensitive subjects with allergic
      rhinitis before and during pollen season. Patients were randomized in a double
      blind fashion and treated with either topical steroids (200 microg fluticasone
      propionate twice daily; n = 16) or matched placebo nasal spray (n = 17) before
      the pollen season. Alkaline phosphatase anti-alkaline phosphatase
      immunocytochemistry was used to identify B cells (CD20+), and in situ
      hybridization was used to detect IL-4, Cepsilon, and Iepsilon RNA+ cells.
      RESULTS: Baseline examination revealed IL-4 and Cepsilon RNA but virtually no
      Iepsilon RNA+ cells in the nasal mucosa. Analysis revealed a significant
      difference in the expression of Cepsilon and Iepsilon RNA+ cells (p < 0.001).
      Biopsy specimens taken after antigen exposure exhibited highly significant
      increases in placebo-treated (p < 0.001) but not steroid-treated patients. In
      both groups, the number of CD20+ cells was unchanged when preexposure and
      postexposure biopsy specimens were compared. CONCLUSIONS: These results show
      strong support for the hypothesis that IgE class switching occurs locally within
      the nasal mucosa of subjects with seasonal allergic rhinitis and that this
      response can be inhibited through strategies directed against local IgE
      production.

PMID- 9525450
TI  - The utility of methacholine airway responsiveness measurements in evaluating anti
      asthma drugs.
AB  - BACKGROUND: Measurements of airway responsiveness are frequently used to evaluate
      anti-asthma drugs. OBJECTIVE: This study investigated the utility of methacholine
      airway responsiveness measurements in evaluating anti-asthma medications, both in
      terms of a bronchoprotective effect and the ability to attenuate allergen-induced
      methacholine airway hyperresponsiveness. METHODS: Methacholine airway
      responsiveness was measured as PC20 on two occasions (separated by 35+/-17 days,
      mean +/- SD) in 40 subjects with mild, stable asthma. Additional subjects had
      PC20 measurements made before and after administration of either inhaled
      salbutamol (200 microg) (n = 20) or allergen inhalation challenge (n = 31).
      RESULTS: The reproducibility of the methacholine PC20 with this method was high
      (intraclass correlation coefficient = 0.94). The average shift in PC20 after
      salbutamol was 4.11 doubling concentrations (SD = 1.08). On the basis of these
      results, a sample size of 12 subjects would be required to demonstrate a 1
      doubling concentration difference in the bronchoprotective effect of two drugs
      with a 90% power. The average shift in PC20 after allergen was 1.29 doubling
      concentrations. On the basis of these results and an estimated SD of 0.96, a
      sample size of 24 subjects would be required to demonstrate that a drug is
      effective in attenuating 50% of allergen-induced airway hyperresponsiveness with
      a 90% power. CONCLUSION: These results confirm the high reproducibility of
      methacholine PC20 measurements in subjects with mild, stable asthma and
      demonstrate its utility in evaluating the effects of anti-asthma drugs.

PMID- 9525451
TI  - Tissue localization of bovine dander allergen Bos d 2.
AB  - BACKGROUND: Domestic mammals are important sources of indoor allergens. However,
      the origin at the tissue level and the biologic function of mammalian allergens
      are largely unknown. OBJECTIVE: The aim of this study was to localize the source
      of the major bovine dander allergen, Bos d 2, in bovine tissues. METHODS: Samples
      from several organs were tested for the presence of mRNA encoding Bos d 2 and Bos
      d 2 protein by using the reverse transcriptase polymerase chain reaction and
      immunohistochemical staining, respectively. RESULTS: Skin proved to be the only
      tissue where mRNA encoding Bos d 2 was detected. This observation was confirmed
      by immunohistochemistry with a monoclonal anti-Bos d 2 antibody as the primary
      antibody. In the skin sections, Bos d 2 was found in the secretory cells of
      apocrine sweat glands and the basement membranes of the epithelium and hair
      follicles. Bos d 2 belongs to the family of lipocalins comprising a number of
      pheromone carrier proteins that are present, for example, in the secretions of
      the apocrine sweat glands. CONCLUSION: Together with earlier data, our findings
      suggest that Bos d 2 is produced in sweat glands and transported to the skin
      surface as a carrier of the pheromone ligand. Because dander allergens of a
      number of mammalian species are lipocalins, the common biologic function of being
      pheromone carriers seems to be a common feature of an important group of
      aeroallergens.

PMID- 9525452
TI  - Immunohistochemical detection of human basophils in late-phase skin reactions.
AB  - BACKGROUND: Human basophils are difficult to detect with classic histochemical
      stains at sites of allergic inflammation. The 2D7 anti-basophil monoclonal
      antibody was used to identify basophils in skin during the late-phase response to
      a cutaneous allergen challenge. METHODS: The 2D7 monoclonal antibody was used on
      protease-digested sections of skin biopsy specimens obtained 6 and 24 hours after
      an allergen or buffer challenge. The skin chamber technique was used to compare
      buffer- and allergen-challenged sites at 6 hours, and intradermal injection of
      allergen was used to compare allergen-challenged sites at 6 and 24 hours.
      RESULTS: Dramatic increases in the numbers of 2D7+ cells and in tissue staining
      by 2D7 were observed 6 hours after allergen challenge compared with buffer
      challenge. Histamine levels in skin chamber fluid varied with 2D7+ cell
      concentrations. By 24 hours, 2D7+ cells and tissue staining appeared to diminish
      but were still detectable in the allergen-challenged sites. Basophils localized
      primarily in and around blood vessels, whereas mast cells remained mostly in the
      superficial dermis. Mast cells were 2D7- in both the allergen- and buffer
      challenged skin. Metachromatic staining of 2D7+ basophils with toluidine blue was
      absent in these tissue sections. CONCLUSIONS: The 2D7 monoclonal antibody
      provides a more sensitive and precise marker than histochemical staining for
      human basophil involvement during the late-phase response to an allergen
      challenge. Basophil infiltration was observed at 6 hours only after allergen
      challenge and persisted at similar levels by 24 hours.

PMID- 9525454
TI  - Sulfonamide-induced reactions in desensitized patients with AIDS--the role of
      covalent protein haptenation by sulfamethoxazole.
AB  - BACKGROUND: Adverse reactions to sulfonamides cause significant morbidity in
      patients with AIDS. We have demonstrated previously a approximately 40 kd
      sulfamethoxazole (SMX)-substituted protein in the serum of some individuals
      treated with SMX. OBJECTIVE: The purpose of this study was to examine patients
      with AIDS who had undergone SMX desensitization because of a prior history of SMX
      allergy for the presence of SMX-haptenated serum proteins and to determine
      whether these proteins, SMX-specific IgG antibodies, or both predict the
      development of subsequent clinical reactivity. METHODS: Four patients with no
      history of allergy and in whom SMX prophylaxis was initiated and eight patients
      with AIDS who had undergone SMX desensitization because of prior allergy were
      evaluated. SMX-conjugated serum proteins were identified with an immunoblotting
      assay, and SMX-specific IgG antibodies were identified by ELISA inhibition.
      RESULTS: One of the four patients receiving SMX prophylactic treatment
      demonstrated SMX-protein haptenation, none had detectable SMX-specific IgG
      antibodies, and none developed an SMX-associated reaction during the time in
      which they were followed. Of the eight patients who underwent SMX
      desensitization, six (75%) demonstrated SMX-protein haptenation, and three of
      these six (50%) subsequently developed SMX-induced cutaneous reactions. Only one
      of these six patients had detectable SMX-specific IgG antibodies. The two
      individuals who did not demonstrate SMX-protein haptenation have not developed a
      clinical reaction. CONCLUSION: These preliminary data suggest that SMX
      haptenation, but not SMX-specific antibodies, may be important in the development
      of clinical sensitivity in patients with AIDS who have undergone SMX
      desensitization.

PMID- 9525453
TI  - Characterization of recombinant Mercurialis annua major allergen Mer a 1
      (profilin).
AB  - BACKGROUND: Two major allergens (Mer a 1A and Mer a 1B), tentatively identified
      as profilin, have been described in the euphorbiacea, Mercurialis annua.
      OBJECTIVES: We sought to clone and characterize these major allergens from M.
      annua pollen and to obtain the immunologically active and soluble recombinant
      allergen, which could then be used for diagnostic procedures and therapy.
      METHODS: Isolation of cDNA clones was performed by polymerase chain reaction
      amplification with degenerate primers. Expression in Escherichia coli BL21 (DE3)
      was carried out with a vector based in the T7 expression system, and the
      recombinant allergen was isolated by affinity chromatography on poly-(L-proline)
      Sepharose. Electrophoretic (sodium dodecylsulfate-polyacrylamide gel
      electrophoresis, isoelectric focusing, and 2-dimensional polyacrylamide gel
      electrophoresis) and immunochemical methods (Western blot and ELISA) were used
      for the characterization of the recombinant allergen. RESULTS: Two cDNA inserts
      coding for M. annua pollen profilin (Mer a 1) were cloned and sequenced. Full
      length Mer a 1 cDNA was expressed in E. coli as nonfusion protein. The final
      yield of recombinant Mer a 1 from the culture media after a single purification
      step on poly-(L-proline)-Sepharose was as much as 5 mg per liter. The reactivity
      of recombinant Mer a 1 with IgE antibodies present in sera from patients allergic
      to M. annua, Olea europaea, and Ricinus communis pollens was comparable to that
      of the natural counterparts, but latex profilin had no cross-reactivity with M.
      annua profilin. Recombinant Mer a 1 was shown to share B-epitopes with sunflower
      profilin. CONCLUSION: This approach is suitable for the production of defined and
      purified recombinant allergens, which could allow more detailed immunologic
      characterization of these proteins and the development of much more accurate
      diagnostic measures and specific anti-allergic treatments.

PMID- 9525455
TI  - Plant defense-related enzymes as latex antigens.
AB  - BACKGROUND: Latex allergy is an increasing hazard to people who frequently come
      into contact with latex products. Of interest concerning this immediate-type
      allergy is the cross-reactivity to various vegetable foods and pollen. Despite
      its high prevalence, no adequate explanation has been provided for the cross
      reactive antigens. OBJECTIVE: We have hypothesized that a series of plant defense
      related proteins act as latex allergens, as well as vegetable food allergens. To
      evaluate this hypothesis, hydrolytic enzymes that are very likely to take on
      defensive roles in rubber trees were examined for their antigenicity. METHODS: By
      applying chromatographic procedures, defense-related enzymes were separated from
      nonammoniated latex (NAL). Their antigenicity was examined by immunoblotting and
      ELISA with sera containing IgE antibodies to crude latex proteins. RESULTS: Three
      kinds of hydrolytic enzymes (basic beta-1,3-glucanases [35, 36.5, and 38 kd], a
      basic chitinase/lysozyme [29.5 kd], and an acidic esterase [44 kd]) were
      separated from NAL. They were recognized by IgE antibodies from a significant
      number of patients allergic to latex. The basic beta-1,3-glucanases and the
      acidic esterase were also strongly recognized by IgE antibodies from several
      atopic subjects who were allergic to various vegetable foods rather than latex
      products. CONCLUSION: It was ascertained that the three defense-related enzymes
      separated from NAL constituted part of the latex antigens. Taking together the
      well-known serologic or immunologic relationships and amino acid sequence
      similarities of defense-related proteins coming from phylogenetically distant
      plant species, we can suspect their universal antigenicity and cross-reactivity.

PMID- 9525456
TI  - Cytokine mRNA expression in asthma is not restricted to the large airways.
AB  - BACKGROUND: Although previous studies have established the presence of an
      eosinophil-rich cellular infiltrate in the small airways of asthmatic lungs, the
      expression of cytokines within the peripheral airways has been largely
      unexplored. The purpose of our study was to test the hypothesis that TH2-type
      cytokines are increased in the peripheral airways and parenchyma of asthmatic
      lungs. METHODS: The presence of messenger ribonucleic acid (mRNA) encoding both T
      helper (TH1)-type (IL-2, interferon-gamma) and TH2-type (IL-4, IL-5) cytokines in
      surgically resected lungs from six asthmatic and 10 nonasthmatic subjects was
      determined by in situ hybridization. Colocalization of IL-5 mRNA within the large
      and small airways was performed by simultaneous in situ hybridization and
      immunocytochemistry. RESULTS: Expression of IL-5 mRNA-positive cells was
      significantly increased in the large and small airways and in the lung parenchyma
      of asthmatic subjects compared with nonasthmatic subjects. In the asthmatic
      individuals, the expression of IL-5 mRNA was increased in the small airways
      compared with the large airways. There was also an increase in the number of
      cells expressing IL-4 mRNA in the large and small asthmatic airways compared with
      the nonasthmatic airways. In contrast, the numbers of IL-2 and interferon-gamma
      mRNA-positive cells did not differ between asthmatic and nonasthmatic
      individuals. CONCLUSIONS: We conclude that there is an increased expression of
      TH2-type cytokines within the peripheral airways of asthmatic lungs and suggest
      that the small airways contribute to the pathophysiology of asthma.

PMID- 9525457
TI  - Immunogenetic analysis of the heavy chain variable regions of IgE from patients
      allergic to peanuts.
AB  - Peanuts are one of the most allergenic of the foods, and hypersensitivity
      responses to peanut allergens can be fatal. Although the nature of the antigenic
      components of peanuts is being defined at the molecular level, there is little
      information on the induced IgE antibodies, which are central to the allergic
      reaction. Recognition sites of IgE antibody molecules arise from the variable
      regions of heavy and light chains (VH and VL). By using nested polymerase chain
      reactions with specific primers for the available repertoire of VH genes,
      together with primers in the constant epsilon region, we have amplified VH
      sequences of IgE from blood lymphocytes of two patients with peanut allergy.
      After cloning and sequencing the products, we found a predominance of VH1 family
      use in both patients, which was not found in control IgM-specific primers. The
      IgE VH sequences were highly somatically mutated, but in only six of 17 cases was
      there clear evidence for clustering of amino acids indicative of antigen
      selection. Previous results from patients with allergy to house dust mites have
      indicated predominance of VH5 use and little evidence for antigen selection.
      Although results from two patients allergic to peanuts must be regarded as
      preliminary, they do suggest that the IgE response to peanuts may have a
      different VH bias, with a similar mutational pattern.

PMID- 9525458
TI  - Antibody responses to bee melittin (Api m 4) and hornet antigen 5 (Dol m 5) in
      mice treated with the dominant T-cell epitope peptides.
AB  - BACKGROUND: Mice treated with the dominant T-cell epitope peptides of allergens
      were reported to have reduced peptide or allergen-specific T-cell responses on
      subsequent immunization, but the extent of reduction of allergen-specific
      antibodies is not clear. OBJECTIVE: This study was done to compare the extent of
      reduction of T-cell and antibody responses in peptide-treated mice. Two allergens
      were tested. Bee melittin (Api m 4), an allergen of 26 amino acid residues, has a
      single dominant T- or B-cell epitope. Hornet antigen 5 (Dol m 5), an allergen of
      204 amino acid residues, has multiple dominant T- or B-cell epitopes. METHODS:
      Mice were treated with T-cell peptides of Api m 4 or Dol m 5 and then immunized
      biweekly with their respective allergen with alum adjuvant. T-cell peptides
      tested were residues 7-19 of Api m 4 and residues 41-60, 141-160, and 176-195 of
      Dol m 5. T-cell responses at week 9 or 11 were assayed by proliferation of spleen
      cell cultures. Antibody responses of different isotypes were measured biweekly by
      ELISA. RESULTS: Partial reduction of 30% to 50% of T-cell responses to peptide or
      allergen was observed in bee and hornet peptide-treated mice. About 65% reduction
      of Api m 4-specific antibody response was observed early in the immune response
      but gradually subsided to about 40% late in the response. Partial reduction of
      about 40% of Dol m 5-specific antibody response was only observed early in the
      immune response. CONCLUSION: Peptide treatment is partially effective in the
      reduction of T-cell responses of univalent or multivalent allergens. It is also
      partially effective in the reduction of antibody response of a univalent
      allergen, but it is poorly effective for a multivalent allergen.

PMID- 9525459
TI  - Complementation of Der P 2-induced histamine release from human basophils
      sensitized with monoclonal IgE: not only by IgE, but also by IgG antibodies
      directed to a nonoverlapping epitope of Der p 2.
AB  - The interaction of free allergen with two (or more) IgE molecules bound to the
      high-affinity receptor for IgE (FcepsilonRI) on mast cells and basophilic
      granulocytes results in the release of inflammatory mediators. The role of
      allergen-specific IgG antibodies in the allergic reaction in human beings is less
      clear. We produced two chimeric IgE antibodies, hIgE-Dp2A and hIgE-Dp2B, directed
      to two nonoverlapping epitopes (A and B) of the house dust mite allergen Der p 2.
      Chimeric IgG1 and IgG4 variants of these antibodies were produced also. Basophil
      activation by the house dust mite allergen Der p 2 was induced after
      sensitization of basophils with a mixture of chimeric hIgE-Dp2A and hIgE-Dp2B
      antibodies but not after sensitization by the individual IgE antibodies alone.
      Basophil activation was also shown after sensitization with hIgE-Dp2A and
      stimulation with Der p 2 incubated with hIgG1-Dp2B or hIgG4-Dp2B antibodies. Both
      IgE and IgG antibodies directed to the other nonoverlapping epitope complemented
      the sensitization by the hIgE-Dp2A antibody. Nonsensitized basophils were not
      activated by the Der p 2/hIgG-Dp2 mixtures. These results indicate that allergen
      specific IgG can complement an IgE-dependent reaction and therefore under certain
      conditions can act as an anaphylactic antibody.

PMID- 9525460
TI  - Effect of fexofenadine on eosinophil-induced changes in epithelial permeability
      and cytokine release from nasal epithelial cells of patients with seasonal
      allergic rhinitis.
AB  - Recent studies have suggested that antihistamines, widely used in the treatment
      of symptoms of patients with allergic rhinitis, may also possess antiinflammatory
      properties. The mechanisms underlying this property, however, are not clearly
      understood. We have cultured epithelial cells from nasal biopsy specimens from
      patients with seasonal allergic rhinitis outside the pollen season and studied
      the effect of 0 to 10(-3) mol/L fexofenadine, the main active metabolite of
      terfenadine, on eosinophil-induced changes in electrical resistance (measure of
      permeability) and release of proinflammatory mediators from these cells.
      Additionally, we have studied the effect of this drug on eosinophil chemotaxis
      and adherence to endothelial cells induced by conditioned medium from these human
      nasal epithelial cell (HNEC) cultures. Incubation of HNEC in the presence of
      eosinophils treated with opsonized latex beads significantly decreased the
      electrical resistance of these cultures, an effect that was abrogated by
      treatment of the cultures with 10(-9) to 10(-3) mol/L fexofenadine. Similarly,
      incubation of HNEC in the presence of eosinophils treated with latex beads also
      significantly increased the basal release of the chemokine "regulated upon
      activation, normal T cell expressed and secreted" (RANTES) (from 96.0 to 613.0
      fg/microg cellular protein; p < 0.05), IL-8 (from 42.0 to 198.5 pg/microg
      cellular protein; p < 0.05), granulocyte-macrophage colony-stimulating factor (GM
      CSF) (from 0.54 to 3.4 pg/microg cellular protein; p < 0.05), and soluble
      intercellular adhesion molecule-1 (sICAM-1) (from 7.8 to 18.4 pg/microg cellular
      protein; p < 0.05) from HNEC. The eosinophil-induced release of IL-8, GM-CSF, and
      sICAM-1 from the HNEC was significantly attenuated by treatment with
      fexofenadine. Analysis of the effects of conditioned medium from HNEC
      demonstrated that this significantly increased both eosinophil chemotaxis and
      adherence to endothelial cells. Addition of 10(-6) to 10(-3) mol/L fexofenadine
      to the conditioned medium significantly attenuated eosinophil chemotaxis and
      adherence to endothelial cells. These results suggest that fexofenadine may
      reduce nasal inflammation by modulating the release of proinflammatory mediators
      and adhesion molecules from HNEC.

PMID- 9525461
TI  - House dust mite allergen (Der p 1) in human hair.

PMID- 9525462
TI  - Guinep fruit anaphylaxis: a case report.

PMID- 9525463
TI  - Recombinant allergens for immunotherapy: a Der p 2 variant with reduced IgE
      reactivity retains T-cell epitopes.

PMID- 9525464
TI  - Adrenal suppression in two patients with asthma treated with low doses of the
      inhaled steroid fluticasone propionate.

PMID- 9525465
TI  - A case of garlic allergy.

PMID- 9525467
TI  - Sting anaphylaxis and urticaria pigmentosa.

PMID- 9525466
TI  - Hypersensitivity reactions to Escherichia coli-derived polyethylene glycolated
      asparaginase associated with subsequent immediate skin test reactivity to E. coli
      derived granulocyte colony-stimulating factor.

PMID- 9525468
TI  - Maternal atopy and childhood bronchial asthma.

PMID- 9525469
TI  - RANTES.

PMID- 9525470
TI  - Truncation of Sp1 transcription factor by myeloblastin in undifferentiated HL60
      cells.
AB  - When HL60 cells are exposed to 1,25-dihydroxyvitamin D3 (1,25D3), they undergo
      changes approximating the phenotype of the monocyte. Little is known, however,
      about the regulation and the mechanisms of this transition. It was previously
      noted that DNA binding by the Sp1 transcription factor in nuclear extracts of
      HL60 cells is profoundly altered when these cells are induced to differentiate by
      1,25D3. In the present study, we show that in untreated HL60 cells only a
      truncated, approximately 30-kDa Sp1 fragment, encompassing the C-terminal region,
      binds to the GC element-containing DNA. Full-length 105-kDa Sp1 protein cannot be
      detected in these cells, although reverse transriptase-polymerase chain reaction
      reveals the presence of both 5' and 3' ends of Sp1 mRNA. Following treatment with
      10(7) M 1,25D3 for 96 hr or in cells made resistant to 1,25D3 or to 1-beta-D
      arabinocytosine, the Sp1 protein can be demonstrated. After an exposure to
      purified myeloblastin, a serine protease, purified recombinant Sp1 protein and
      extracts of 1,25D3-treated cells show a pattern of DNA binding similar to the
      pattern seen using extracts of untreated HL60 cells, indicating that the Sp1
      protein is a target for myeloblastin. Because myeloblastin is present in naive
      HL60 cells and is downregulated during their differentiation, inhibition of
      proteolysis of these transcription factors seems to provide a mechanism through
      which differentiating HL60 cells can acquire a new repertoire of gene expression,
      perhaps for the maintenance of the differentiated phenotype.

PMID- 9525471
TI  - Hypotonic Ca2+ signaling and volume regulation in proliferating and quiescent
      cells from multicellular spheroids.
AB  - Hypotonicity-induced Ca2+ signals and volume regulation were studied in
      proliferating and quiescent subpopulations of multicellular prostate cancer
      spheroids. Enzymatic dissociation of multicellular spheroids 100+/-19 microm in
      diameter, which are entirely proliferative, yielded a population of cells with a
      mean cell diameter of 17.5+/-1.4 microm. After dissociation of spheroids in a
      size class of 200+/-30, 300+/-60, and 400+/-65 microm in diameter, two
      subpopulations of cells with mean cell diameters corresponding to 12.9+/-1.9
      microm and 16.7+/-2 microm were discriminated. The subpopulation of large cells
      was shown to be proliferative by positive Ki-67 antibody staining; the
      subpopulation of small cells was Ki-67 negative, indicating cell quiescence. In a
      spheroid size class of 100+/-19 microm, a distinct subpopulation of quiescent
      cells was absent. Superfusion by hypotonic solutions revealed that only the
      proliferating cell fraction showed a regulatory volume decrease (RVD) and a
      [Ca2+]i transient. Both effects were absent in the quiescent cell population. The
      [Ca2+]i transient persisted in low (10 nM) Ca2+ solution and in the presence of 4
      mM extracellular Ni2+ but was abolished in the presence of the endoplasmic
      reticulum Ca2+-ATPase blocker 2,5-di-tert-butyl-hydrochinone (t-BHQ). The t-BHQ
      likewise inhibited RVD, indicating that Ca2+ release from intracellular stores
      was necessary for RVD. Moreover, [Ca2+]i and RVD were dependent on an intact
      microfilament cytoskeleton because after 30 min of preincubation with
      cytochalasin B the [Ca2+]i transient was significantly reduced and RVD was
      abolished. The absence of RVD and [Ca2+]i transient in quiescent cells may be due
      to differences in the amount and the cytosolic arrangement of F-actin observed in
      quiescent cells.

PMID- 9525473
TI  - Vitronectin decreases microvascular endothelial cell apoptosis.
AB  - Angiogenesis after tissue injury occurs in a matrix environment consisting of
      fibrin, fibronectin, and vitronectin as the major extracellular matrix (ECM)
      constituents. ECM-integrin interactions is critical for angiogenesis and failure
      to bind a ligand to certain integrin receptors (alpha[v]beta3 or alpha[v]beta5)
      inhibits angiogenesis. The ligand that binds to alpha(v)beta3 or alpha(v)beta5
      integrin receptors during microvascular angiogenesis has not been identified. Our
      hypothesis is that provisional matrix molecules provide the environmental context
      cues to microvascular endothelial cells and promote angiogenesis by decreased
      programmed cell death. Using cultured human microvascular endothelial cells, we
      show that vitronectin, in comparison to growth on alternative provisional matrix
      molecules (fibronectin, fibrinogen plus thrombin), collagen I, and basement
      membrane molecules (collagen IV), significantly reduces microvascular endothelial
      cell death in vitro. This reduction was observed using morphologic criteria, TdT
      mediated dUTP nick end labeling (TUNEL) assay, histone release into the
      cytoplasm, and thymidine release into the supernatant. Though our data confirm
      that vitronectin may bind to more than one integrin receptor to reduce MEC
      apoptosis, binding to the alpha(v) component appears to be the critical integrin
      subcomponent for reducing apoptosis.

PMID- 9525472
TI  - Insulin-like growth factor-I promotes multidrug resistance in MCLM colon cancer
      cells.
AB  - Insulin-like growth factor-I (IGF-I) is known as a potent mitogen for a variety
      of cell types, including colon cancer cell lines. The objective of this study was
      to determine the effect of IGF-I on cell death induced by cytotoxic agents
      actinomycin D (Act-D), lovastatin (LOV), and doxorubicin (DOX) in the MCLM mouse
      colon cancer cell line, and the mechanisms involved. Subconfluent monolayer MCLM
      cells were treated with IGF-I (25 ng/ml) for 12 h in serum-free media. Various
      concentrations of cytotoxic agents then were added to the cells that were
      incubated continually at 37 degrees C for 24 h. Cell survival was determined with
      the MTT (3-[4-5-dimenthylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay,
      which assesses mitochondrial function in living cells. The mRNA expression for
      multidrug resistance gene-1 (mdr-1), c-H-ras, and manganese superoxide dismutase
      (MnSOD) in cells treated with IGF-I was examined by Northern blot or RNase
      protection assays. The levels of p-glycoprotein, a drug efflux pump encoded by
      the mdr-1 gene, were assessed by Western immunoblotting. Results demonstrated
      that 1) IGF-I significantly inhibited the cell death and apoptosis of MCLM cells
      treated with Act-D, LOV, or DOX; 2) IGF-I increased mRNA expression for mdr-1, c
      H-ras, and MnSOD; 3) the p-glycoproteins in cells treated with IGF-I or stably
      transfected with c-H-ras were elevated when compared with control. These results
      suggest that IGF-I protects MCLM cells against death induced by cytotoxic agents;
      this acquired drug resistance may be mediated by multiple mechanisms, including
      promoting expression of mdr-1, c-H-ras, and MnSOD; whereas, the p-glycoprotein
      level stimulated by IGF-I may result partly from the increase of c-H-ras in the
      cells.

PMID- 9525474
TI  - Increase of reactive oxygen species (ROS) in endothelial cells by shear flow and
      involvement of ROS in shear-induced c-fos expression.
AB  - Intracellular reactive oxygen species (ROS) may participate in cellular responses
      to various stimuli including hemodynamic forces and act as signal transduction
      messengers. Human umbilical vein endothelial cells (ECs) were subjected to
      laminar shear flow with shear stress of 15, 25, or 40 dynes/cm2 in a parallel
      plate flow chamber to demonstrate the potential role of ROS in shear-induced
      cellular response. The use of 2',7'-dichlorofluorescin diacetate (DCFH-DA) to
      measure ROS levels in ECs indicated that shear flow for 15 minutes resulted in a
      0.5- to 1.5-fold increase in intracellular ROS. The levels remained elevated
      under shear flow conditions for 2 hours when compared to unsheared controls. The
      shear-induced elevation of ROS was blocked by either antioxidant N-acetyl
      cysteine (NAC) or catalase. An iron chelator, deferoxamine mesylate, also
      significantly reduced the ROS elevation. A similar inhibitory effect was seen
      with a hydroxyl radical (.OH) scavenger, 1,3-dimethyl-2-thiourea (DMTU),
      suggesting that hydrogen peroxide (H202), .OH, and possibly other ROS molecules
      in ECs were modulated by shear flow. Concomitantly, a 1.3-fold increase of
      decomposition of exogenously added H2O2 was observed in extracts from ECs sheared
      for 60 minutes. This antioxidant activity, abolished by a catalase inhibitor (3
      amino-1,2,4-triazole), was primarily due to the catalase. The effect of ROS on
      intracellular events was examined in c-fos gene expression which was previously
      shown to be shear inducible. Decreasing ROS levels by antioxidant (NAC or
      catalase) significantly reduced the induction of c-fos expression in sheared ECs.
      We demonstrate for the first time that shear force can modulate intracellular ROS
      levels and antioxidant activity in ECs. Furthermore, the ROS generation is
      involved in mediating shear-induced c-fos expression. Our study illustrates the
      importance of ROS in the response and adaptation of ECs to shear flow.

PMID- 9525476
TI  - Expression of TGFalpha autocrine activity in human colon carcinoma CBS cells is
      autoregulated and independent of exogenous epidermal growth factor.
AB  - Autocrine transforming growth factor alpha (TGFalpha) activity and control
      mechanisms for its expression were examined in a representative clonal isolate
      (CBS4) of a well-differentiated human colon carcinoma cell line designated CBS.
      CBS4 cells expressed TGFalpha and its receptor, epidermal growth factor receptor
      (EGFr). Blockade of EGFr and TGFalpha by neutralizing antibodies inhibited clonal
      growth and the initiation of DNA synthesis from quiescence in CBS4 cells.
      Therefore, TGFalpha is an autocrine growth factor for CBS4 cells. Several studies
      have indicated that activation of the EGFr by exogenous EGF stimulates TGFalpha
      expression. However, in CBS4 cells EGF did not induce TGFalpha mRNA expression,
      indicating that EGF does not affect TGFalpha transcription in these cells.
      Exogenous treatment of exponentially growing cells with either EGF or EGFr
      blocking antibody enhanced release of TGFalpha protein into the conditioned
      medium. This indicated that the release of TGFalpha into the conditioned medium
      by exogenous EGF was at least partially due to the displacement of TGFalpha from
      the TGFalpha/EGFr complexes. Similarly to exponentially growing cells, the EGFr
      blocking antibody and EGF also enhanced TGFalpha release into the medium of CBS4
      cells after release from quiescence. These results indicated that exogenous EGF
      had little if any effect on TGFalpha expression in these cells and suggested that
      TGFalpha expression might be under endogenous TGFalpha control. Blockade of the
      autocrine TGFalpha loop by TGFalpha neutralizing antibody suppressed TGFalpha
      mRNA both in exponentially growing and quiescent cells, demonstrating that
      autocrine TGFalpha is autoregulatory in this system.

PMID- 9525475
TI  - Adhesion to fibronectin or collagen I gel induces rapid, extensive, biosynthetic
      alterations in epithelial cells.
AB  - Extracellular matrix influences many cellular events. In this study, we
      demonstrate that adhesion of human salivary gland (HSG) epithelial cells to
      fibronectin- or collagen I gel-coated substrates, mediated by beta1 integrins,
      results in substantial alterations in protein and RNA expression profiles. The
      large numbers of changes in expression suggest that simply changing the adhesive
      substrate has basic effects on the regulation of cellular biosynthesis. Two
      dimensional electrophoresis of [35S]methionine-labeled HSG cell proteins
      identified significant differences in the patterns of protein expression by cells
      cultured on nonprecoated substrates, collagen I gels or fibronectin. Thirty-two
      differentially expressed cDNA clones, which included both novel and previously
      sequenced genes, were up-regulated within 6 hr by culturing HSG cells on
      fibronectin or collagen I gels. Therefore, adhesion to collagen I or fibronectin
      resulted in rapid, widespread changes in cellular biosynthetic control.
      Expression of some genes was induced by ligation of beta1 integrins with
      antifunctional antibodies, whereas the expression of other genes was not induced.
      Most of the differentially expressed genes were up-regulated by adhesion to both
      fibronectin- and collagen I gel-coated substrates, but a few genes were
      selectively up-regulated on only one substrate. Furthermore, the up-regulated
      expression of some genes was detected within 3 hr, whereas changes in others
      required 6 hr. Discrete adhesive substrates and integrin molecules differentially
      affected the expression of a significant number of genes, suggesting that the
      cellular responses to adhesion were triggered through several signaling pathways.

PMID- 9525477
TI  - The role of transforming growth factor-beta1, -beta2, and -beta3 in androgen
      responsive growth of NRP-152 rat prostatic epithelial cells.
AB  - We have investigated the role of autocrine/paracrine TGF-beta secretion in the
      regulation of cell growth by androgens as demonstrated by its inhibition by two
      androgen response modifiers; the nonsteroidal antiandrogen hydroxyflutamide
      (OHF), believed to act by inhibiting androgen binding to androgen receptors, or
      finasteride, an inhibitor of 5alpha-reductase, the enzyme necessary for the
      conversion of testosterone to 5alpha-dihydrotestosterone (DHT), using the
      nontumorigenic rat prostatic epithelial cell line NRP-152. Growth of these cells
      was stimulated three- to sixfold over control by either testosterone or DHT under
      serum-free culture conditions. This was accompanied by a two- to threefold
      decrease in the secretion rate of TGF-beta1, -beta2, and -beta3. Finasteride
      reversed the ability of testosterone but not DHT to stimulate growth and
      downregulate expression of TGF-beta1, -beta2, and -beta3 in a dose-dependent
      fashion, suggesting that this activity of testosterone required its conversion to
      DHT. OHF antagonized the stimulatory effects of DHT on NRP-152 cell growth but
      could reverse the inhibitory effects of DHT only on TGF-beta2 and TGF-beta3 and
      not TGF-beta1 secretion. This suggests that either TGF-beta1 regulation by DHT or
      the androgen antagonism of OHF occurs independent of androgen receptor binding.
      Neutralizing antibodies to TGF-beta (pantropic and isoform-specific) were able to
      block the ability of finasteride to antagonize the effects of testosterone nearly
      completely while only partially inhibiting the antiandrogenic effects of OHF.
      Thus, the ability of androgens to stimulate growth of NRP-152 cells involves the
      downregulation of the production of TGF-beta1, -beta2, and -beta3 in addition to
      other growth-stimulatory mechanisms.

PMID- 9525478
TI  - Intracellular calcium requirements for beta1 integrin activation.
AB  - Human polymorphonuclear leukocytes (PMNs) express beta1 integrins that mediate
      adhesion to extracellular matrix proteins following stimulation with agonists
      that induce an increase in intracellular calcium. The purpose of these studies
      was to determine the contribution made by alterations in intracellular calcium
      ([Ca++]i) to inside-out activation of beta1 integrins using dimethyl sulfoxide
      (DMSO)-differentiated granulocytic HL60 cells as a model of human PMNs.
      Activation of beta1 integrins was determined by measuring the expression of an
      activation-dependent epitope on the beta1 subunit that is recognized by
      monoclonal antibody (mAb) 15/7. Exposure of granulocytic HL60 cells to calcium
      ionophore ionomycin (800 nM) alone did not increase the binding of mAb 15/7 to
      the cell surface, nor did it increase beta1 integrin-mediated adhesion of the
      cells to fibronectin. Similarly, exposure of the cells to the direct protein
      kinase C (PKC) activator, dioctanoylglycerol (di-C8) at 100 microM, neither
      increased binding of mAb 15/7 to these cells nor adhesion to fibronectin.
      Simultaneous addition of di-C8 and ionomycin, however, caused a significant
      increase in the expression of the 15/7 epitope and cell adhesion, suggesting
      synergy between elevating [Ca++]i and stimulating PKC in beta1 integrin
      activation. Chelation of [Ca++]i with Quin-2 and EGTA reduced both basal
      (unstimulated) expression of the 15/7 epitope and basal adhesion of granulocytic
      HL60 cells to fibronectin. In addition, chelation of [Ca++]i caused a significant
      decrease in 15/7 binding and adhesion stimulated by low (1 ng/ml) concentrations
      of phorbol myristate acetate (PMA). The inhibitory effect of [Ca++]i chelation on
      beta1 integrin activation was reversed by repleting [Ca++]i with ionomycin in a
      Ca++-containing buffer, or by the addition of higher concentrations of PMA (10
      ng/ml). These data suggest a role for [Ca++]i in inside-out activation of beta1
      integrins, probably through a synergistic effect with PKC activation.

PMID- 9525479
TI  - Expression of azurophil and specific granule proteins during differentiation of
      NB4 cells in neutrophils.
AB  - Neutrophils contain several populations of secretory granules with characteristic
      sets of proteins. Granule proteins are sorted into their respective granule types
      by temporal regulation of their expression during cell differentiation and/or by
      specific targeting signals. We investigated the expression of some granule
      proteins in human promyelocytic NB4 cells. Like other myeloid cell lines which
      can be differentiated into neutrophils, NB4 cells lack the specific-granule
      population. We report here that, nevertheless, they express the specific-granule
      matrix protein lactoferrin, when differentiated with retinoic acid. Lactoferrin
      and the azurophil-granule protein beta-glucuronidase were simultaneously
      expressed, whereas myeloperoxidase expression had stopped, showing that azurophil
      granule proteins are not all produced concomitantly. Cell fractionation by
      Percoll gradient revealed that while beta-glucuronidase co-fractionated with
      myeloperoxidase, lactoferrin was mostly contained in a vesicular compartment free
      of markers for azurophil granules, plasma membrane, and Golgi. This vesicular
      compartment was not implicated in regulated exocytosis since it was not mobilized
      by secretagogues, which, in parallel, induced the release of myeloperoxidase.
      Furthermore, the specific granule-membrane protein cytochrome b558 also became
      expressed during NB4-cell differentiation. However, it did not co-localize with
      lactoferrin but was present in the plasma-membrane fraction. Therefore,
      differentiation of NB4 cells with retinoic acid leads to the expression of
      specific- and azurophil-granule proteins and provides a unique cell line model to
      study the mechanisms involved in the sorting of azurophil- and specific-granule
      proteins.

PMID- 9525480
TI  - Protein tyrosine phosphorylation and calcium signaling in thyroid FRTL-5 cells.
AB  - We examined the importance of tyrosine kinase(s) on the ATP-evoked Ca2+ entry and
      DNA synthesis of thyroid FRTL-5 cells. ATP rapidly and transiently tyrosine
      phosphorylated a 72-kDa protein(s). This phosphorylation was abolished by
      pertussis toxin and by the tyrosine kinase inhibitor genistein, and was dependent
      on Ca2+ entry. Pretreatment of the cells with genistein did not affect the
      release of sequestered Ca2+, but the capacitative Ca2+ or Ba2+ entry evoked by
      ATP or thapsigargin was attenuated. Pretreatment of the cells with orthovanadate
      enhanced the increase in intracellular free Ca2+ ([Ca2+]i), whereas the Ba2+
      entry was not increased. Phorbol 12-myristate 13-acetate (PMA) phosphorylated the
      same protein(s) as did ATP. Genistein inhibited the ATP-evoked phosphorylation of
      MAP kinase and attenuated both the ATP- and the PMA-evoked DNA synthesis.
      However, genistein did not inhibit the ATP-evoked expression of c-fos.
      Furthermore, genistein enhanced the ATP-evoked release of arachidonic acid. Thus,
      ATP activates a tyrosine kinase via a Ca2+-dependent mechanism. A genistein
      sensitive mechanism participates, in part, in the ATP-evoked activation of DNA
      synthesis. Genistein inhibits only modestly capacitative Ca2+ entry in FRTL-5
      cells.

PMID- 9525481
TI  - Constitutive activation of Jak-2 and Tyk-2 in a v-Src-transformed human
      gallbladder adenocarcinoma cell line.
AB  - It is well known that v-Src phosphorylates various substrates on tyrosine residue
      and associates with tyrosine-phosphorylated proteins as well as proline-rich
      ligands through its SH2 and SH3 domains, respectively, thereby inducing oncogenic
      transformation. A signal pathway from the cell surface to genes in the nucleus,
      the Jak/STAT (signal transducers and activators of transcription) pathway, has
      been shown to be involved in the signal transduction mechanism mediated by many
      cytokines and growth factors. Although a member of the STAT family, STAT3 has
      been reported to be constitutively activated in several v-Src-transformed cells,
      and it still remains unknown whether Jak molecules, which act upstream of STATs,
      are involved in the v-Src-induced activation mechanism of STAT3. In this study,
      we analyzed activations of both Jak and STAT molecules using v-Src-transformed
      HAG-1 cells derived from a human gallbladder adenocarcinoma. STAT3 was found to
      be constitutively activated in v-Src-transformed HAG-1 cells, but not in either
      non-transformed mock-transfected or activated c-H-ras-transfected HAG-1 cells,
      even though the other known STAT molecules are expressed. Furthermore, both Jak-2
      and Tyk-2 were constitutively activated only in v-Src-transformed HAG-1 cells.
      Association of v-Src with either STAT3 or the Jak molecules was not observed. No
      change of this activation was detected by either interferon (IFN)-alpha2a or IFN
      gamma, which had shown inhibitory effects on the growth of v-Src-transformed HAG
      1 cells. These results raise the possibility that Jak-2 and Tyk-2 are both
      activated by v-Src, thereby contributing to the constitutive activation of STAT3
      in the v-Src-transformed cells.

PMID- 9525482
TI  - Coordinate expression of OPN and associated receptors during monocyte/macrophage
      differentiation of HL-60 cells.
AB  - Promyelocytic leukemia HL-60 cells promoted by PMA to differentiate along the
      monocyte pathway adhere to tissue culture plates. To explore the regulation of
      adhesion molecules in cells promoted to differentiate, the expression and
      secretion of osteopontin (OPN) and expression of associated cell surface
      receptors, CD44 and integrin subunits alpha(v), beta3, beta1, were examined.
      Results were as follows: 1) PMA induced OPN mRNA and OPN secretion into media; 2)
      untreated cells expressed beta1 and CD44 mRNA, and PMA induced alpha(v), and
      beta3 mRNA and increased beta1 and CD44 mRNA expression; 3) PMA increased levels
      of alpha(v), beta3, beta1 and CD44 protein on the cell surface; and 4) retinoic
      acid, which promotes granulocytic differentiation of HL-60 cells, did not affect
      OPN, alpha(v), beta3, beta1, or CD44 mRNA or protein expression. These data
      suggest that induction of OPN and associated receptors may play a role during
      monocytic differentiation of HL-60 cells.

PMID- 9525483
TI  - Historical ties between otolaryngology-head and neck surgery and aviation and
      space medicine.
AB  - Otolaryngology-head and neck surgeons have been involved in the development of
      aviation and space medicine since the beginning of this century. More than 75
      years ago, otolaryngologists revised the physical examination for pilots,
      organized "boards of medical examiners" to test pilot applicants, coined the term
      "flight surgeon," and helped organize the first medical research laboratories at
      Hazelhurst Field in New York. These laboratories were transformed in 1922 into
      the School of Aviation Medicine at Brooks Field, Texas, which in turn
      subsequently was relocated to Randolph Field, Texas. During World War II the
      Director of Research at the school was Colonel Paul A. Campbell, MD, an
      otolaryngologist. In 1959, the school moved back to Brooks Air Force Base and was
      renamed the Aerospace Medical Center. Since manned space flight began in the
      1960s there have been many joint research efforts between principal investigators
      in otolaryngology-head and neck surgery and NASA. Several otolaryngology-head and
      neck surgeons have served or currently serve as consultants and advisors to many
      of NASA's standing committees. The space environment offers a new frontier for
      development and research in the specialty and for better understanding of
      vestibular function and related disorders.

PMID- 9525484
TI  - Physiological principles of vestibular function on earth and in space.
AB  - Physiological mechanisms underlying vestibular function have important
      implications for our ability to understand, predict, and modify balance processes
      during and after spaceflight. The microgravity environment of space provides many
      unique opportunities for studying the effects of changes in gravitoinertial force
      on structure and function of the vestibular system. Investigations of basic
      vestibular physiology and of changes in reflexes occurring as a consequence of
      exposure to microgravity have important implications for diagnosis and treatment
      of vestibular disorders in human beings. This report reviews physiological
      principles underlying control of vestibular processes on earth and in space.
      Information is presented from a functional perspective with emphasis on signals
      arising from labyrinthine receptors. Changes induced by microgravity in linear
      acceleration detected by the vestibulo-ocular reflexes. Alterations of the
      functional requirements for postural control in space are described. Areas of
      direct correlation between studies of vestibular reflexes in microgravity and
      vestibular disorders in human beings are discussed.

PMID- 9525486
TI  - Synaptic changes in rat maculae in space and medical imaging: the link.
AB  - Two different space life sciences missions (SLS-1 and SLS-2) have demonstrated
      that the synapses of the hair cells of rat vestibular maculae increase
      significantly in microgravity. The results also indicate that macular synapses
      are sensitive to stress. These findings argue that vestibular maculae exhibit
      neuroplasticity to macroenvironmental and microenvironmental changes. This
      capability should be clinically relevant to rehabilitative training and/or
      pharmacological treatments for vestibular disease. The results of this
      ultrastructural research also demonstrated that type I and type II hair cells are
      integrated into the same neuronal circuitry. The findings were the basis for
      development of three-dimensional reconstruction software to learn details of
      macular wiring. This software, produced for scientific research, has now been
      adapted to reconstruct the face and skull directly from computerized tomography
      scans. In collaboration with craniofacial reconstructive surgeons at Stanford
      University Medical Center, an effort is under way to produce a virtual
      environment workbench for complex craniofacial surgery. When completed, the
      workbench will help surgeons train for and simulate surgery. The methods are
      patient specific. This research illustrates the value of basic research in
      leading to unanticipated medical applications.

PMID- 9525485
TI  - Molecules, motion, and man.
AB  - The application of cell and molecular biology techniques to vestibular research
      is resulting in rapid changes in our understanding of the fundamental mechanisms
      of vestibular function. The clinical problems encountered in space travel
      together with the acute and chronic vestibular dysfunction affecting many of the
      patients otolaryngologists care for have driven this research at a rapid pace. A
      review of these methods and highlights of the major advances are discussed.

PMID- 9525487
TI  - Countermeasures for vestibular dysfunction.

PMID- 9525488
TI  - Spaceflight influences on ocular counterrolling and other neurovestibular
      reactions.
AB  - Exposure to extended periods of weightlessness in orbital flight has profound
      effects on the neurovestibular system and influences head and eye movements,
      postural control, and spatial orientation. The associated space motion sickness
      is among the earliest of the signs of adaptation to this new environment. This
      report both reviews the prominent neurovestibular phenomena associated with going
      into space and returning to earth and relates the issues to vestibular
      compensation and rehabilitation. New results from the Spacelab SLS-2 mission are
      included, showing significant reductions in postflight ocular counterrolling and
      changes in ocular counterrolling left/right asymmetries after 2 weeks in space.

PMID- 9525489
TI  - Clinical use of three-dimensional video measurements of eye movements.
AB  - Noninvasive measurements of three-dimensional eye position can be accurately
      achieved with video methods. A case study showing the potential clinical benefit
      of these enhanced measurements is presented along with some thoughts about
      technological advances, essential for clinical application, that are likely to
      occur in the next several years.

PMID- 9525490
TI  - Vestibulospinal adaptation to microgravity.
AB  - Human balance control is known to be transiently disrupted after spaceflight;
      however, the mechanisms responsible for postflight postural ataxia are still
      under investigation. In this report, we propose a conceptual model of
      vestibulospinal adaptation based on theoretical adaptive control concepts and
      supported by the results from a comprehensive study of balance control recovery
      after spaceflight. The conceptual model predicts that immediately after
      spaceflight the balance control system of a returning astronaut does not expect
      to receive gravity-induced afferent inputs and that descending vestibulospinal
      control of balance is disrupted until the central nervous system is able to cope
      with the newly available vestibular otolith information. Predictions of the model
      are tested using data from a study of the neurosensory control of balance in
      astronauts immediately after landing. In that study, the mechanisms of
      sensorimotor balance control were assessed under normal, reduced, and/or altered
      (sway-referenced) visual and somatosensory input conditions. We conclude that the
      adaptive control model accurately describes the neurobehavioral responses to
      spaceflight and that similar models of altered sensory, motor, or environmental
      constraints are needed clinically to predict responses that patients with
      sensorimotor pathologies may have to various visual-vestibular or changing
      stimulus environments.

PMID- 9525491
TI  - Computerized dynamic posturography: What have we learned from space?
AB  - Computerized dynamic posturography (CDP) has been under development since 1970.
      Several reviews summarize key basic and clinical research studies and outline
      important clinical uses of CDP along with research applications. This report
      summarizes new information about the otolith control of posture obtained from the
      study of astronauts. The dynamics of recovery of postural control upon return
      from orbital flight provide insight to the peripheral vestibular and central
      nervous system components of vestibular compensation. The dynamics of postural
      compensation should aid the clinician in the diagnosis and management of
      imbalance of vestibular origin.

PMID- 9525493
TI  - From DNA damage to cell death: the role of nuclear structure in the response to
      cancer therapy. Overview of the proceedings: from loose loops to sticky ends.

PMID- 9525492
TI  - Cardiovascular effects of microgravity: evolution of understanding.
AB  - The understanding of cardiovascular effects of spaceflight has evolved throughout
      the course of the American manned spaceflight program. Originally descriptive in
      nature, the present understanding is based on empiric measurements of vascular
      volume, cardiac output, vascular reflexes, and peripheral and central autonomic
      control. More detailed understanding of cardiovascular effects has allowed us to
      separate those symptoms from symptoms caused by musculoskeletal or
      neurovestibular abnormalities.

PMID- 9525494
TI  - Alterations in chromosome structure and variations in the inherent radiation
      sensitivity of human cells.
AB  - Variations in the inherent radiosensitivity of both tumor cells and the normal
      tissues that surround them play an important role in tumor response to radiation
      therapy. In vitro studies suggest that variations in radiation sensitivity both
      between different tissues and within a specific histology are a reflection of
      differences in the rate and fidelity of rejoining of chromosome breaks. Cells of
      radiosensitive cell lines rejoin breaks more slowly and with less fidelity than
      those of more resistant cell lines. Differences in radiation sensitivity are also
      associated with variations in chromosome structure as detected by nucleoid-based
      assays. A model is presented to suggest that the radiation sensitivity of a cell
      line is a reflection of its transcriptional architecture, the number and genomic
      location of its actively transcribing regions. Also, it is proposed that
      chromosome breaks induced at or near transcriptionally active regions of the
      genome are rejoined preferentially and with greater fidelity than breaks induced
      at other regions of the genome.

PMID- 9525495
TI  - Direct evidence that transgene integration is random in murine cells, implying
      that naturally occurring double-strand breaks may be distributed similarly within
      the genome.
AB  - We have examined the distribution of illegitimate integration of a transgene
      within the genome of cells of a murine fibroblast cell line, LTA, using
      fluorescence in situ hybridization (FISH) analysis. The transgene vector
      contained specific sequences for detection via FISH and a hygromycin resistance
      gene for selection. Cells were transfected via CaPO4, and pools of 250 to 3000
      hygromycin-resistant clones were subjected to FISH analysis. The integration of
      the transgene was scored for chromosome morphology (acrocentric, metacentric or
      dicentric) and position (relative to centromere or telomere). More than 90% of
      the hygromycin-resistant clones observed involved integration of the transgene
      singly or as multiple copies, at a single site within the genome. No bias was
      observed for integration of the transgene in any particular chromosome morphology
      or chromosomal position, even in the presence, within the genome, of sequences
      homologous to the transgene. This study presents direct evidence that
      illegitimate integration of a transgene occurs randomly in murine fibroblasts.
      Since it is postulated that initiation of illegitimate recombination involves a
      double-strand break (DSB), a corollary to the above results would be that
      naturally occurring DSBs also occur randomly within the murine genome.

PMID- 9525496
TI  - Desferrioxamine enhances the effects of gamma radiation on clonogenic survival
      and the formation of chromosomal aberrations in endothelial cells.
AB  - Vascular injury and endothelial damage contribute to the efficacy and
      complications of radiotherapy. Iron chelation protects against iron-catalyzed
      oxidative injury, but it also inhibits DNA synthesis in proliferating cells and
      can cause apoptosis. We examined the prevailing effects of iron chelation on the
      survival of gamma-irradiated human umbilical vein endothelial cells by treating
      monolayers, primarily in the G1/G0 phase of the cell cycle, with the iron
      chelator desferrioxamine for 24 h prior to gamma irradiation. Desferrioxamine
      treatment alone diminished plating efficiency by inducing apoptosis and delaying
      proliferation; this effect disappeared by 48 h. Desferrioxamine treatment reduced
      clonogenic survival after exposure to 2.5 Gy gamma radiation, but neither iron
      loading with hemin nor treatment with another iron chelator, 2,2-dipyridyl, which
      is a potent inhibitor of ribonucleotide reductase, had an effect on survival
      after irradiation. Clonogenic survival and chromosomal aberrations were measured
      in parallel in endothelial cells treated with desferrioxamine after increasing
      doses of gamma radiation. In a linear-quadratic model of survival,
      desferrioxamine treatment did not change the occurrence of directly lethal
      lesions, but it significantly increased sublethal injury. Desferrioxamine was not
      clastogenic alone, but it increased the frequency of formation of chromosomal
      rings and of excess acentric fragments after gamma irradiation.

PMID- 9525497
TI  - Effect of pentoxifylline on radiation-induced G2-phase delay and radiosensitivity
      of human colon and cervical cancer cells.
AB  - Cells of three adherent cell lines with mutated p53 (WiDr and C33-A) and
      disrupted p53 (C4-I) were used to investigate the effect of pentoxifylline (PTX)
      on radiation-induced G2-phase block and its relationship to radiosensitivity.
      Postirradiation exposure to 0.25-1.0 mM PTX resulted in an increase in
      radiosensitivity in a concentration-dependent manner as determined by a
      clonogenic assay. The change in radiation sensitivity was quantified by
      calculating the enhancement ratio (ER) at a clinically relevant dose of 2 Gy; the
      ER for WiDr cells was 1.23+/-0.03 and 1.39+/-0.15 for 0.5 and 1.0 mM PTX,
      respectively. For C33-A cells, the ER ranged from 1.04+/-0.04 to 1.99+/-0.17 for
      0.25-1.0 mM PTX, whereas for C4-I cells the values were 1.29+/-0.04 and 1.76+/
      0.17 for 0.25 and 0.5 mM PTX. In asynchronous WiDr, C33-A and C4-I cells, flow
      cytometry analysis showed a dose-dependent accumulation of cells in G2/M phase
      which was detectable at 6 h and peaked at 12 h after irradiation. Such a G2/M
      phase block was transient at a dose of 2 Gy and persisted at 48 or 72 h after a
      dose of 4 or 6 Gy. At 12 h after 2 Gy, PTX significantly reduced the radiation
      induced G2/M-phase block in a dose-dependent manner. After the higher doses of 4
      and 6 Gy, the dose-dependent G2-phase arrest was significantly alleviated at 24 h
      by treatment with PTX, and the kinetics of this alleviation depended on the
      radiation dose. The results demonstrate that human colon and cervical cancer
      cells characterized by a mutated or disrupted p53 (i.e. not transfected) are
      radiosensitized by PTX, which alleviates the postirradiation G2/M-phase block.

PMID- 9525498
TI  - Persistent decrease in viability as a function of X irradiation of human bladder
      carcinoma cells in G1 or S phase.
AB  - A persistent decrease in viability after treatment with a variety of mutagenic
      agents has been observed previously, but the dependence of the decrease on the
      phase of the cell cycle in which the cells are treated has not been fully
      explored. Synchronous human bladder carcinoma cells (EJ30-15) were obtained by
      mitotic selection (88-96% in or near mitosis). As monitored by microscopy and
      pulse labeling with [3H]dThd, approximately 98% of the cells were in G1 phase
      when they were irradiated after 3 h of incubation, and approximately 80% were in
      S phase when they were irradiated after 14 h of incubation. The initial plating
      efficiencies demonstrated no difference in cell survival when cells were
      irradiated in G1 or S phase, with normalized clonogenic survival and standard
      error of 60+/-6% for 3 Gy and 13+/-2% for 6 Gy. However, when the cell
      populations were allowed to incubate and were replated 5 to 33 days later (5.5 to
      36 doublings), a difference between the populations irradiated in G1 and S phase
      became clear. Cells that were irradiated with 6 Gy regained and maintained the
      high plating efficiencies (67.9+/-3.6%) of the unirradiated populations much
      sooner when they were irradiated in S phase compared with irradiation in G1
      phase, i.e. 11 days (12 cell doublings) for S phase compared to approximately 20
      days (22 cell doublings) for G1 phase. During these periods when the plating
      efficiencies were increasing, the populations irradiated in G1 phase were
      multiplying at rates lower than those for the populations irradiated in S phase.
      Furthermore, after 6 Gy, more giant cells and multinucleated cells were seen in
      the populations irradiated in G1 phase than in the populations irradiated in S
      phase. These results indicate that, although the clonogenic survival was the same
      for cells irradiated in G1 or S phase, the residual damage in progeny of the
      irradiated cells persisted longer (approximately 20 days compared to 11 days)
      when cells were irradiated in G1 phase than when they were irradiated in S phase.

PMID- 9525499
TI  - Serial in vivo observations of cerebral vasculature after treatment with a large
      single fraction of radiation.
AB  - To test whether single high doses of radiation, similar to those used with
      radiosurgery, given to normal cerebral vasculature can cause changes in leukocyte
      vessel wall interactions and tissue perfusion, a rat pial window model was used
      to view the cerebral vasculature, facilitating repeated in vivo observations of
      microcirculatory function. An attachment for a 4 MV linear accelerator was
      designed to deliver a well-collimated 2.2-mm beam of radiation to a selected
      region of rat brain. Sequential measurements of leukocyte-endothelial cell
      interactions, relative change in blood flow with laser Doppler flowmetry and
      vessel length density were performed prior to and at 24 h and 3 weeks after
      treatment with 15, 22.5 or 30 Gy, given in a single fraction. Significant
      increases in leukocyte-endothelial cell interactions were seen 24 h and 3 weeks
      after irradiation that were dependent on dose, particularly in arteries. Changes
      were apparent in both arteries and veins at 24 h, but by 3 weeks the effects in
      arteries predominated. Decreases in vessel length density and blood flow were
      observed and became greater with time after treatment. A variety of morphological
      changes were observed in irradiated arteries, including formation of aneurysmal
      structures, endothelial denudation and thrombus formation. These results suggest
      that: (1) An increase in leukocyte-vessel wall interactions occurs after
      irradiation; (2) cerebral arterioles are more sensitive than veins to radiation
      administered in this fashion; and (3) the increase in leukocyte-vessel wall
      interactions likely contributes to reduction of or loss of arteriolar flow, with
      resultant loss of flow to dependent microvascular vessels.

PMID- 9525500
TI  - Diurnal variations in the expression of radiation-induced apoptosis.
AB  - Experiments were performed to determine whether diurnal variations in apoptosis
      in the mouse small intestine after irradiation with 2.5 Gy gamma rays depended on
      the time of day that the mice were irradiated, the time of day that the mice were
      sacrificed or the interval between irradiation and sacrifice. Experiments were
      performed with a 12-h light:dark regimen with the light period from 6:00 to 18:00
      h. With fixed intervals of 6 h and 24 h between irradiation and sacrifice, a peak
      in induced apoptosis (16%) was observed in mice sacrificed at 8:00 h, two times
      higher than the nadir of response at 23:00 h (8%). When variable intervals were
      used between irradiation and measurement of apoptosis, i.e. sacrifice, at 8:00 h
      or 23:00 h, the induced apoptosis was dependent on the interval, with a peak for
      18-h intervals. However, the level of apoptosis was always about twofold higher
      when measured at 8:00 h than at 23:00 h. No correlation was observed between
      diurnal variations in apoptosis and survival of mouse intestinal crypts. The
      diurnal variations in apoptosis after irradiation can be interpreted either in
      terms of expression of apoptosis during the G2/M phase of the cell cycle in
      partially synchronized cells, or in terms of a systemic mechanism such as diurnal
      variation in the neurohormone melatonin.

PMID- 9525501
TI  - Lung cancer risk due to exposure to incorporated plutonium.
AB  - An epidemiological study has been carried out among 1,479 male workers who
      started working at the "Mayak" Production Association in 1948-1958 and were
      exposed to external gamma radiation and plutonium aerosols. Lung cancer mortality
      for the follow-up period 1948-1993 has been analyzed. No statistically
      significant association of lung cancer mortality and external gamma-ray dose has
      been revealed in the range of accumulated doses of 0.2-5.5 Gy. Association of
      lung cancer mortality and the dose of alpha-particle radiation to the lung is
      statistically significant. In the dose range below 30 Sv, this association can be
      described in terms of a linear nonthreshold function. Lifetime lung cancer risk
      in the dose range below 30 Sv is 1.21 x 10(-2)Sv(-1).

PMID- 9525502
TI  - A semiquantitative histological analysis of repair of anastomoses in the rat
      colon after combined preoperative irradiation and local hyperthermia.
AB  - Hyperthermia is a promising method for increasing the efficacy of radiation
      therapy of colorectal cancer. To study the histological aspects of healing of an
      anastomosis in the colon, after combined preoperative (sham) irradiation and
      (sham) hyperthermia treatment, 48 male Wistar rats were divided randomly into
      four groups. In each animal, a segment of the colon was treated successively by
      (sham) irradiation (single dose of 25 Gy X rays) and/or (sham) hyperthermia (44
      degrees C, 30 min). After 5 days, a resection of the colon was performed by
      construction of an anastomosis: The distal limb consisted of (sham-) irradiated
      and/or (sham-) hyperthermia-treated bowel. Rats were killed 3 or 7 days after the
      surgical procedure. Evaluation of healing of the anastomosis was made by: (1)
      histological analysis of sections stained with hematoxylin and eosin, (2)
      semiquantitative measurement of collagen in the area of the anastomosis and (3)
      semiquantitative analysis of the number of macrophages by immunocytochemistry.
      Healing of the anastomoses in animals receiving irradiation or hyperthermia alone
      and in control animals was relatively uneventful. There were no differences
      between groups in formation of collagen or infiltration by macrophages in the
      area of the anastomosis. Animals treated with both radiation and hyperthermia
      showed marked necrosis, infiltration by polymorphonuclear leukocytes and rupture
      of the anastomosis. It is concluded that preoperative irradiation with a single
      dose of 25 Gy in combination with local hyperthermia at 44 degrees C for 30 min
      leads to disturbed repair of anastomoses.

PMID- 9525503
TI  - The compound factor of the 10B(n,alpha)7Li reaction from borocaptate sodium and
      the relative biological effectiveness of recoil protons for induction of brain
      damage in boron neutron capture therapy.
AB  - To make clinical trials of boron neutron capture therapy safe for patients, it is
      necessary to know the relative biological effectiveness (RBE) of the radiation
      components and the compound factor of the boron carrier to be used. Here a method
      is derived to determine the RBE of recoil protons and the compound factor of
      compounds from in vivo experiments with different concentrations of boron. The
      method uses a simultaneous fit of both these parameters to all experimental data.
      This method is applied to the studies of tolerance of healthy tissue in dogs at
      the High Flux Reactor in Petten, The Netherlands. The RBE for the recoil protons
      generated by the neutrons present in the epithermal neutron beam [together with
      the RBE of the protons from the 14N(n,p)14C reaction] for induction of severe
      neurological symptoms was found to be 3.93+/-0.43 (95% confidence limits 3.06
      4.79), and 2.33+/-0.14 (2.04-2.61) for induction of changes detectable by
      magnetic resonance imaging. The compound factor for Na2B12H11SH in brain tissue,
      using severe neurological symptoms as end point, was determined to be 0.37+/-0.06
      (95% confidence limits 0.24-0.50). For changes detectable by magnetic resonance
      imaging, the value was found to be 0.65+/-0.04 (0.58-0.73).

PMID- 9525504
TI  - Wall effects observed in tissue-equivalent proportional counters from 1.05
      GeV/nucleon iron-56 particles.
AB  - Tissue-equivalent proportional counters (TEPCs) have been used to measure energy
      deposition in simulated volumes of tissue ranging in diameter from 0.1 to 10
      microm. There has been some concern that the wall used to define the volume of
      interest could influence energy deposition within the sensitive volume because it
      has a density significantly greater than that of the cavity gas. These effects
      become important for high-velocity heavy ions. Measurements of energy deposition
      were made for 1 GeV/nucleon iron particles in a TEPC simulating a 1-microm
      diameter sphere of tissue. The TEPC was nested within a particle spectrometer
      that provided identification and flight path of individual particles. Energy
      deposition was studied as a function of pathlength through the TEPC.
      Approximately 30% of the energy transfer along trajectories through the center of
      the detector escapes the sensitive volume. The response of the TEPC, for
      trajectories through the detector, is always larger than calculations for energy
      loss in a homogeneous medium. This enhancement is greatest for trajectories near
      the cavity/wall interface. An integration of the response indicates that charged
      particle equilibrium is essentially achieved for a wall thickness of 2.54 mm.
      However, estimates of the linear energy transfer for the incident particles are
      influenced by these wall effects.

PMID- 9525505
TI  - Detection of DNA damage by the alkaline comet assay after exposure to low-dose
      gamma radiation.
AB  - The alkaline comet assay as described by Olive et al. (Exp. Cell Res. 198, 259
      267, 1992) was used to detect DNA damage in cells exposed to low doses (0-5 cGy)
      of gamma radiation. Experiments were performed using lymphocytes isolated from
      whole blood of rats. The comet parameters, normalized comet moment and comet
      length, described by Kent et al. (Int. J. Radiat. Biol. 67, 655-660, 1995), were
      used as measurements of DNA damage. It was observed that the alkaline comet assay
      can detect DNA damage at doses as low as 0.6 cGy. The results of the experiments
      using low-dose gamma radiation are comparable with published results obtained
      using the alkaline comet assay according to the method of Singh et al. (Int. J.
      Radiat. Biol. 66, 23-28, 1994). Based on this observation and analysis of results
      published previously, we conclude that the version of the alkaline comet assay
      described by Olive et al. is as sensitive as other modifications of the comet
      assay reported in literature for the detection of DNA damage in cells exposed to
      low doses of ionizing radiation.

PMID- 9525506
TI  - Postirradiation sarcomas in Sprague-Dawley rats.
AB  - A series of radiation-induced neoplasms occurred in Sprague-Dawley rats 4-8
      months after irradiation of a single hind leg with 60Co gamma rays. The rats were
      exposed to fractionated cumulative doses that ranged from 0 to 106 Gy.
      Osteosarcomas, malignant fibrous histiocytomas and fibrosarcomas developed in the
      radiation fields of a number of the rats in the higher-dose groups. Tumors did
      not develop throughout an 8-month observation period in rats that received doses
      of only 0 or 46 Gy. The most common postirradiation sarcomas in humans are
      osteosarcoma, malignant fibrous histiocytoma and fibrosarcoma. The Sprague-Dawley
      rat may serve as a good animal model in studying the development of sarcoma in
      humans after regional radiotherapy.

PMID- 9525507
TI  - Sound- and/or pressure-induced vertigo due to bone dehiscence of the superior
      semicircular canal.
AB  - OBJECTIVES: To present symptoms, patterns of nystagmus, and computed tomographic
      scan identification of patients with sound- and/or pressure-induced vertigo due
      to dehiscence of bone overlying the superior semicircular canal. To describe
      anatomical findings and outcome in 2 patients undergoing plugging of the superior
      semicircular canal for treatment of these symptoms. DESIGN AND SETTING:
      Prospective study of a case series in a tertiary care referral center. PATIENTS
      AND RESULTS: Eight patients with vertigo, oscillopsia, and/or disequilibrium
      related to sound, changes in middle ear pressure, and/or changes in intracranial
      pressure were identified in a 2-year period. Seven of these patients also had
      vertical-torsional eye movements induced by these sound and/or pressure stimuli.
      The direction of the evoked eye movements could be explained by excitation or
      inhibition of the superior semicircular canal in the affected ear. Computed
      tomographic scans of the temporal bones identified dehiscence of bone overlying
      the affected superior semicircular canal in each case. Disabling disequilibrium
      in 2 patients prompted plugging of the dehiscent superior canal through a middle
      cranial fossa approach. Symptoms were improved in each case. One patient
      developed recurrent symptoms requiring an additional plugging procedure and
      developed sensorineural hearing loss several days after this second procedure.
      CONCLUSIONS: We have identified patients with a syndrome of vestibular symptoms
      induced by sound in an ear or by changes in middle ear or intracranial pressure.
      These patients can also experience chronic disequilibrium. Eye movements in the
      plane parallel to that of the superior semicircular canal were evoked by stimuli
      that have the potential to cause ampullofugal or ampullopetal deflection of this
      canal's cupula in the presence of a dehiscence of bone overlying the canal. The
      existence of such deshiscences was confirmed with computed tomographic scans of
      the temporal bones. Surgical plugging of the affected canal may be beneficial in
      patients with disabling symptoms.

PMID- 9525508
TI  - Cell proliferation and apoptosis in human middle ear cholesteatoma.
AB  - OBJECTIVE: To compare the pattern of proliferation and apoptotic cell death in
      cholesteatoma tissues with that in normal skin. PARTICIPANTS: The cholesteatoma
      tissue samples were excised from 10 patients during surgery. Normal skin
      specimens collected from the external ear canal of 6 of the 10 patients were used
      as controls. RESULTS: In all cholesteatoma tissue samples, apoptotic cells were
      not seen in the basal cell layer, but they were observed in the suprabasal,
      prickle, and granular cell layers. In skin specimens obtained from normal
      external ear canal skin, in which the suprabasal cell layer was comparatively
      small, similar kinetics of apoptotic cell death were observed.
      Immunohistochemical analysis using a monoclonal antibody to proliferation cell
      nuclear antigen demonstrated the presence of proliferating cells in the basal and
      suprabasal cell layers of the normal external ear canal skin, whereas in the
      cholesteatoma tissue samples, large numbers of proliferation cell nuclear antigen
      positive cells were also observed in the prickle and granular cell layers.
      CONCLUSIONS: Proliferation in cholesteatoma epidermal cells is not uncontrolled,
      as it is in malignant tumors. Our results demonstrate an increase in the rate of
      proliferation and apoptotic cell death in cholesteatoma epidermis.

PMID- 9525509
TI  - Short- and long-term results with implantable transcutaneous and percutaneous
      bone-conduction devices.
AB  - OBJECTIVES: To compare the percutaneous bone-anchored hearing aid (BAHA; type NBC
      HC-200, Nobel Biocare, Gothenburg, Sweden) and the transcutaneous temporal bone
      stimulator (TBS; Xomed-Treace, Jacksonville, Fla) with conventional hearing aids
      and to evaluate long-term results. DESIGN: In a prospective clinical study, the
      new implantable bone-conduction devices were compared with the patients' previous
      conventional hearing aids. Speech perception in quiet and in noise were studied,
      and a questionnaire concerning the actual use of the device and speech
      recognition was administered. During follow-up that exceeded 4 1/2 years,
      relevant technical and medical problems were documented. PATIENTS: Forty-one
      successive subjects who were fitted with a BAHA and 17 subjects who were fitted
      with a TBS. RESULTS: In most subjects who had previously used a bone-conduction
      device, the new BAHA and TBS devices led to improved or comparable results on
      speech recognition tests and the questionnaire. However, among the subjects who
      had previously used air-conduction hearing aids, the results were ambiguous. In
      the long-term, the percentage of nonusers in the BAHA group was 5% (2/39); in the
      TBS group, 65% (13/20). The main reasons for not using the TBS were insufficient
      gain and medical and technical problems. The vulnerability of the percutaneous
      coupling of the BAHA to trauma or inflammation was not a major issue; only 4
      implants were lost during the total follow-up of more than 250 years. CONCLUSION:
      Results indicate that the BAHA is the better choice.

PMID- 9525510
TI  - Intraindividual comparison of the bone-anchored hearing aid and air-conduction
      hearing aids.
AB  - BACKGROUND: Some patients have to stop using their air-conduction hearing aid(s)
      because it causes or exacerbates chronic otitis. Then, a solution is the use of a
      bone-conduction hearing aid such as the percutaneous bone-anchored hearing aid
      (BAHA). OBJECTIVE: To compare patients' performance with their previous air
      conduction hearing aid(s) and their BAHA using audiometric tests and a
      questionnaire. DESIGN: Prospective clinical evaluation in a single subject
      design. PATIENTS: The results of 34 consecutive patients from the Nijmegen, the
      Netherlands, BAHA series were included. The patients had bilateral conductive or
      mixed hearing loss and chronic ear problems. Before the BAHA was fitted, the
      patients used air-conduction hearing aids. RESULTS: The results of the speech
      recognition in noise test showed a small but significant improvement with the
      BAHA. This improvement was related to the size of the air-bone gap. The greater
      the air-bone gap, the poorer the results with the air-conduction hearing aid(s).
      The questionnaire demonstrated that the majority of patients preferred the BAHA;
      diminished occurrence of ear infections played a significant role. The patients
      did not express an evident preference concerning speech recognition. CONCLUSIONS:
      In patients with chronic ear problems a BAHA is an acceptable alternative if an
      air-conduction hearing aid is contraindicated. Preoperative assessment of the
      size of the air-bone gap is of some help to predict whether speech recognition
      may improve or deteriorate with the BAHA compared with the air-conduction hearing
      aid.

PMID- 9525511
TI  - Complications of tympanostomy tubes inserted for facilitation of hyperbaric
      oxygen therapy.
AB  - OBJECTIVE: To document the incidence of complications occurring secondary to
      placement of tympanostomy tubes in patients undergoing hyperbaric oxygen therapy.
      DESIGN: Retrospective chart review. SETTING: Tertiary referral center. PATIENTS:
      Forty-five patients referred to the Department of Otolaryngology for inability to
      tolerate hyperbaric oxygen therapy between January 1, 1990, and December 31,
      1995. INTERVENTIONS: All patients underwent bilateral myringotomy and tube
      placement. OUTCOME MEASURES: Charts were reviewed for complications of tube
      placement, including otorrhea, otalgia, hearing loss, persistent perforations,
      and tinnitus. RESULTS: Seventeen (38%) of 45 patients experienced complications,
      with most having more than 1. Most complications occurred after conclusion of
      hyperbaric oxygen therapy. Otorrhea was most common, occurring in 13 patients
      (29%). Persistent tympanic membrane perforations occurred in 7 patients (16%).
      CONCLUSIONS: The rate of complications is higher than reported for placement of
      tympanostomy tubes in other patient populations. Coexisting illness, such as
      diabetes mellitus, may contribute to the development of complications in patients
      undergoing hyperbaric oxygen therapy. Alternative methods of tympanostomy, with
      emphasis on shorter duration of intubation, should be considered in this patient
      population.

PMID- 9525512
TI  - Iatrogenic airway stenosis with recurrent respiratory papillomatosis.
AB  - OBJECTIVE: To describe the presentation of, factors contributing to, and
      treatment of iatrogenic airway stenosis (IAS) associated with recurrent
      respiratory papillomatosis (RRP). DESIGN: Retrospective case series. SETTING:
      Pediatric tertiary care center. PATIENTS: The charts of patients treated for RRP
      in our institution from 1980 to 1995 (N=50) were reviewed. Seven patients were
      identified as having IAS based on endoscopic findings. MAIN OUTCOME MEASURES:
      Prevalence and types of IAS within our RRP patient population, methods used to
      treat IAS, and successful treatment of IAS. RESULTS: Of the 7 patients
      identified, 3 had isolated posterior glottic stenosis (PGS) and 1 had isolated
      subglottic stenosis. The other 3 had multiple areas of IAS as follows: PGS with
      bronchial stenosis, supraglottic stenosis with PGS, and tracheomalacia with
      tracheal stenosis from a suprastomal granuloma. The factors associated with IAS
      were extensive papilloma growth in the posterior glottis, prolonged periods of
      frequent laryngoscopies, and the use of nonstandard therapies, which in our
      series included topical podophyllum resin or photodynamic therapy. Six patients,
      all of whom had tracheal RRP at some point in their disease process, required
      tracheotomy. Five patients required laryngotracheal reconstruction.
      Laryngotracheal reconstruction permitted decannulation in all cases. Tracheal
      papillomas became sessile and nonobstructive after decannulation. Laryngotracheal
      reconstruction with rib grafting was most frequently performed. Of our 50
      patients, none who did not have IAS required a tracheotomy. Of the 44 patients
      who did not require a tracheotomy, only 1 had tracheal papillomas. CONCLUSIONS:
      Occasionally, therapy for RRP is complicated by IAS. In our series, PGS was most
      common. Tracheotomy was associated with the presence of both IAS and distal RRP.
      In selected cases, laryngotracheal reconstruction can be successfully
      accomplished when RRP is present, and subsequent regression of tracheal RRP is
      likely.

PMID- 9525513
TI  - First branchial cleft anomalies: a study of 39 cases and a review of the
      literature.
AB  - OBJECTIVES: To identify the clinical and anatomical presentations and to discuss
      the guidelines for surgical management of anomalies of the first branchial cleft.
      DESIGN: Retrospective study. SETTING: Three tertiary care centers. PATIENTS:
      Thirty-nine patients with first branchial cleft anomalies operated on between
      1980 and 1996. INTERVENTION: All patients were treated surgically. Complete
      removal of the lesion required superficial parotidectomy with facial nerve
      dissection in 36 cases. The relationship of the facial nerve and anomalies is
      discussed. RESULTS: Anatomically, 3 types of first branchial cleft anomalies are
      identified: fistulas (n=11), sinuses (n=20), and cysts (n=8). Clinically, 3 types
      of presentation are noted: chronic purulent drainage from the ear (n=12),
      periauricular swelling in the parotid area (n=18), and abscess or persistent
      fistula in the neck located above a horizontal plane passing through the hyoid
      bone (n=21). A membranous attachment between the floor of the external auditory
      canal and the tympanic membrane was observed in 10% of cases. The facial nerve
      was located lateral to the anomaly in 39% of cases. CONCLUSIONS: Before
      definitive surgery, many patients (n=17) underwent incision and drainage for
      infection owing to the difficulties in diagnosing this anomaly. Wide exposure is
      necessary in most cases, and a standard parotidectomy incision allows adequate
      exposure of the anomaly and preservation of the facial nerve. Complete removal
      without complications depends on a good understanding of regional embryogenesis,
      a knowledge of the circumstances surrounding discovery, an awareness of the
      different anatomical presentations, and a readiness to identify and protect the
      facial nerve during resection.

PMID- 9525514
TI  - The Shaw scalpel and development of facial nerve paresis after superficial
      parotidectomy.
AB  - OBJECTIVE: To evaluate the independent relationship of the Shaw scalpel on the
      development of facial nerve injury in patients undergoing superficial
      parotidectomy. METHODS: A retrospective review of 77 cases between 1991 and 1996.
      Forty-eight percent of the surgical procedures were performed using the Shaw
      scalpel, and 52% were performed using a cold knife. To assess whether use of the
      Shaw scalpel is an independent predictor of facial nerve injury, both univariate
      analysis and regression analysis were used in the statistical analysis of the
      data. RESULTS: Fifty-four percent of the patients who underwent a parotidectomy
      in which the Shaw scalpel was used developed postoperative facial weakness,
      compared with 14% of those who underwent a cold knife parotidectomy (P=.002).
      CONCLUSION: Multivariate analysis revealed that use of the Shaw scalpel
      represents an independent risk factor for development of facial nerve weakness
      after parotidectomy (P=.01), even after other risk factors are controlled for.

PMID- 9525515
TI  - The external branch of the superior laryngeal nerve: its topographical anatomy as
      related to surgery of the neck.
AB  - OBJECTIVE: To determine the possible courses of the external branch of the
      superior laryngeal nerve (EBSLN) and its relationship to the superior thyroid
      artery (STA) to improve the chances of identifying and saving the nerve during
      head and neck surgery. DESIGN: Anatomical analysis of the exact topography of the
      EBSLN. SUBJECTS: Thirty-one perfusion-fixed human cadavers (ie, 62 preparations)
      of both sexes ranging in age from 50 to 94 years (mean, 78 years) with neither
      enlarged thyroid glands nor any other signs of abnormality in this region.
      RESULTS: Four types of relationship between the EBSLN, the upper pole of the
      thyroid gland, and the STA were found. In 23 preparations (42%), the EBSLN
      crossed the STA more than 1 cm above the upper pole of the thyroid gland (type
      1). In 15 preparations (30%), the EBSLN crossed the STA less than 1 cm above the
      upper pole of the thyroid gland (type 2). In 7 preparations (14%), the EBSLN
      crossed the STA under cover of the upper pole of the thyroid gland (type 3). In 7
      preparations (14%), the EBSLN descended dorsal to the artery and only crossed the
      branches of the STA immediately above the upper pole of the thyroid gland (type
      4). CONCLUSION: The description of the variable course of the EBSLN and its
      categorization may help minimize the risk of iatrogenic lesions of the nerve
      during surgery.

PMID- 9525516
TI  - Effects of basic fibroblast growth factor on irradiated porcine skin flaps.
AB  - OBJECTIVE: To determine the vascular and collagen effects of supplemental basic
      fibroblast growth factor (bFGF) in irradiated porcine skin flaps. INTERVENTION:
      Animals were subjected to 2 fractions of 650 cGy orthovoltage radiation.
      Following this, the skin flaps were administered bFGF intracuticularly for 6 days
      before and after surgery. The animals were sacrificed 3 weeks after the start of
      bFGF administration. Tissues were analyzed for vascularity, collagen content,
      wound-breaking strength, and histopathological analysis. RESULTS: The bFGF
      treated flaps showed a 62% increase in vascularity compared with controls
      (10.4%+/-2.4% vs 6.43%+/-2.27%; P<.05). The bFGF flaps had a significantly lower
      collagen concentration compared with control flaps when measured by
      hydroxyproline content (0.0619+/-0.0211 nm/microg vs 0.0784+/-0.0150 nm/microg).
      Wound-breaking strength was not significantly different, although the bFGF flaps
      had a trend toward lower breaking strength. Histologically, the bFGF-treated
      flaps showed increased cellularity, fibroblasts, and extracellular
      mucopolysaccharides compared with controls. CONCLUSIONS: This study provides
      evidence that supplemental bFGF can increase vascularity to skin flaps in
      previously irradiated porcine skin tissue. Histologically, radiation did not
      prevent the angiogenic effect of bFGF.

PMID- 9525517
TI  - Measurement of facial movement with computer software.
AB  - OBJECTIVE: To adapt desktop computer software to objectively grade facial
      movement. DESIGN: The criteria of the facial nerve grading system by House and
      Brackmann, the current "gold standard," are prone to ambiguous interpretation.
      Proposed objective grading systems compare the movement of points on each side of
      the face or use subtraction and thresholding of digitized images of the face to
      yield images that represent moving areas of the face. The movement of a point on
      the face and the area of motion determined by digital subtraction were compared
      during an increasing smile in healthy subjects. The Nottingham system (calculated
      using measurement of the movement of 4 points on the face) using desktop computer
      software (Adobe Photoshop 3.0, Adobe Systems Inc, Mountain View, Calif) to
      measure movement of the points was compared with the system by House and
      Brackmann. The computer software was used to subtract digitized images and derive
      a facial movement score, which was compared with the scores of the systems by
      Nottingham and House and Brackmann. SETTING: Academic otologic practice. STUDY
      PARTICIPANTS: Nine patients with varying degrees of facial nerve disability and 7
      individuals with normal facial nerve function. RESULTS: The movement of the oral
      commissure compared with the apparent area of movement of the face determined by
      digital subtraction had high intersubject variability. In patients with facial
      weakness, the Nottingham score had a correlation coefficient of -0.97 compared
      with the House and Brackmann grade, and the digital subtraction score had a
      correlation coefficient of -0.62 (paired Student t test). CONCLUSIONS: The
      desktop computer software can be used to calculate the Nottingham score. Digital
      subtraction as a measure of facial function warrants further study.

PMID- 9525519
TI  - Multispecialty approach to complex dermatofibrosarcoma protuberans of the
      forehead.
AB  - We describe a 38-year-old woman with extensive dermatofibrosarcoma protuberans of
      the forehead and discuss the advantages of using a multispecialty approach in the
      treatment of this case. The patient had had an incomplete resection 15 years
      previously, with a misdiagnosis of the actual tumor type. After undergoing a
      biopsy and a computed tomographic scan, the patient underwent Mohs micrographic
      surgery, followed by split-thickness grafting. Ultimate reconstruction was
      performed 15 months later using bilateral temporoparietal fascial flaps, in
      addition to split-thickness grafting. The patient remains tumor-free 3 years
      after resection.

PMID- 9525518
TI  - Chemical browlift.
AB  - OBJECTIVE: To determine if the medial brow can be elevated following
      administration of botulinum toxin type A (Botox, Allergan, Irvine, Calif).
      DESIGN: A before-after interventional study comparing pretreatment and
      posttreatment brow height. Objective measurements and subjective comparisons of
      pretreatment and posttreatment slides were made by 7 independent observers
      unaware of treatment status. All measurements and observations were based on
      standardized photographs taken with identical lens settings. SETTING: Private
      facial plastic surgery practice. All injections were performed in office
      examination rooms without anesthesia or sedation. PATIENTS: Thirty adult patients
      electively seeking improvement of glabellar frown lines or low-positioned medial
      brows (angry appearance). INTERVENTION: Twenty units of botulinum toxin type A
      was injected into the corrugator supercilli and procerus muscles. An
      electromyographic needle was used for the initial 10 injections, and a 30-gauge
      needle was used for the remainder. OUTCOME MEASURES: In the objective arm, change
      in brow height was measured from the medial canthus and midpupil directly
      vertical to the brow hairs; the change in interbrow distance was also measured.
      In the subjective arm, the number of patients who were found to have an elevated
      medial brow by the independent observers was noted. Objective and subjective
      findings were correlated. RESULTS: Objective measurements yielded a raise in the
      medial brow in 8 (32%) of 25 patients from the medial canthus and in 12 (48%) of
      25 from the midpupil and an increase in interbrow distance in 17 (59%) of 29
      patients. Subjective comparison found 18 (62%) of the 29 patients to have higher
      medial brows after treatment. CONCLUSIONS: Botulinum toxin type A treatment can
      create a chemical browlift. Further studies with more specific selection criteria
      are needed to better evaluate this effect.

PMID- 9525521
TI  - The use of 3-dimensional models in auricular reconstruction.
AB  - Reconstruction of the microtic auricle is a difficult process requiring
      considerable experience and dedication to detail. It is a multistage proposition
      requiring the talents of both the reconstructive surgeon and the otologic
      surgeon. Reconstruction of the external ear usually precedes the reconstruction
      of the middle ear. Often, a template is used by the reconstructive surgeon to aid
      in this complicated process. Traditionally, templates used by the reconstructive
      surgeon have been 2 dimensional (usually x-ray paper) and made from the opposite
      normal ear or another normal ear in cases of bilateral microtia. Use of a 2
      dimensional model only provides a rough estimate of the cartilage framework
      needed. Considerable experience is therefore needed to get this cartilage
      framework "just right." We have developed a number of 3-dimensional synthetic
      templates to aid in the creation of an accurate cartilage framework implant.
      These templates serve as a more accurate guide in the complex cartilage carving
      and assembly process. The use of 3-dimensional templates has improved our
      technical reconstructive results in a small number of patients. We present these
      results and propose future application of these ideas.

PMID- 9525522
TI  - Imaging quiz case 1. Absence of the olfactory bulb and tracts consistent with
      Kallmann syndrome.

PMID- 9525520
TI  - Endonasal endoscopic dacryocystorhinostomy in children.
AB  - OBJECTIVE: To describe the indications, technique, and results of endonasal
      endoscopic dacryocystorhinostomy in children with congenital and acquired
      disorders of the nasolacrimal system. DESIGN: Retrospective case series. SETTING:
      Tertiary care hospital. PATIENTS: Four children ranging in age from 10 months to
      6 years. INTERVENTION: Primary or revision endonasal endoscopic
      dacryocystorhinostomy performed via a joint otolaryngologic-ophthalmologic team
      approach. MAIN OUTCOME MEASURES: Incidence of surgical complications and
      postoperative clinical status. RESULTS: The duration of follow-up was 10 to 24
      months with a successful clinical outcome in all 4 children. Two procedures were
      complicated by nasal vestibule skin abrasions secondary to rotation of the drill
      shaft. CONCLUSIONS: Despite the technical challenges posed by the small
      anatomical dimensions of the pediatric nasal airway, the combination of proper
      otolaryngologic endoscopic instrumentation and ophthalmologic lacrimal sac
      transillumination guidance allows for the safe and successful performance of
      endonasal endoscopic dacryocystorhinostomy in the pediatric population.

PMID- 9525523
TI  - Imaging quiz case 2. Tuberculous mastoiditis causing a facial palsy.

PMID- 9525524
TI  - Selective neck dissection of anatomically appropriate levels is as efficacious as
      modified radical neck dissection for elective treatment of the clinically
      negatice neck in patients with squamous cell carcinoma of the upper respiratory
      and digestive tracts.

PMID- 9525525
TI  - Selective neck dissection in patients with squamous cell carcinoma of the upper
      respiratory and digestive tracts: a lack of adequate data.

PMID- 9525526
TI  - Selective neck dissection: the challenge of occult metastases.

PMID- 9525527
TI  - Biologic plausibility in causal inference: current method and practice.

PMID- 9525528
TI  - Differential misclassification and the assessment of gene-environment
      interactions in case-control studies.
AB  - In case-control studies of interactions between genetic and environmental
      exposures, differential misclassification of the environmental exposure with
      respect to disease status can introduce spurious heterogeneity of the stratum
      specific odds ratios. In this paper, the authors identify conditions under which
      differential misclassification does not introduce bias in the interaction
      parameter when no multiplicative interaction is present, and it biases the
      interaction parameter toward the null value when a multiplicative interaction is
      present. The conditions are that (i) conditional on potential confounders, the
      environmental exposure is independent of the genotype among the controls, and
      (ii) misclassification of the environmental exposure is nondifferential with
      respect to the genotype. These conditions can be tested from the misclassified
      data in the control group, since a test of the independence of the genotype and
      the misclassified environmental exposure among the controls is a test of the
      joint hypothesis that conditions (i) and (ii) are both true. Therefore, the
      authors propose a two-step test for interaction which first tests conditions (i)
      and (ii) and then goes on to test for interaction, provided the first step
      hypothesis is not rejected. A summary test procedure to test for gene-environment
      interactions in the presence of misclassification, based on both a conventional
      test for interaction and the two-step test, is recommended, and is illustrated
      with data from a case-control study of the role of diet as a modifier of the
      association between a metabolic polymorphism and lung cancer.

PMID- 9525529
TI  - Pregnancy is not associated with the progression of HIV disease in women
      attending an HIV outpatient program.
AB  - The objective of this study was to determine whether pregnancy is associated with
      an acceleration of human immunodeficiency virus (HIV) disease progression in
      women who have a pregnancy while HIV infected. A retrospective review of all
      women aged 15-35 years who attended an HIV outpatient program from January 1989
      through August 1995, was undertaken. The 192 women who had a term pregnancy after
      testing positive for HIV were compared with 164 women who were not pregnant
      during the same period. The main outcome measures were death, the occurrence of a
      first acquired immunodeficiency syndrome (AIDS)-defining condition, or a
      condition indicative of symptomatic HIV. Disease progression was assessed using
      the Kaplan-Meier method and multivariate proportional hazards models. Compared
      with nonpregnant women, women with a term pregnancy were significantly more
      likely to be African-American (88% vs. 78%, p < 0.05), younger than 22 years of
      age (51 % vs. 11%, p < 0.001), and to have entered the clinic with a higher
      median CD4 count (519 vs. 433 cells/microl, p < 0.001). After adjusting for entry
      CD4 count and other factors, pregnancy was not associated with progression to any
      of the study outcomes. Thus, in women attending a publicly funded clinic,
      pregnancy does not appear to accelerate the progression of HIV disease.

PMID- 9525530
TI  - Factors of the insulin resistance syndrome in nondiabetic and diabetic elderly
      Japanese-American men.
AB  - Factor analysis has previously identified four independent factors that
      characterize the insulin resistance syndrome in women, interpreted as 1)
      weight/waist, 2) lipids, 3) insulin/glucose, and 4) systolic and diastolic blood
      pressure. Because it is not known whether similar factors emerge for men, or for
      diabetics, factor analysis was used to investigate the clustering of features
      characterizing the insulin resistance syndrome using data from 3,159 elderly (71
      93 years) Japanese-American men participating in the fourth examination of the
      Honolulu Heart Program during 1991-1993. Consistent with previous results, factor
      analysis reduced eight risk factors (insulin, glucose, systolic blood pressure,
      diastolic blood pressure, triglycerides, high-density lipoprotein cholesterol,
      weight, and waist circumference) to four uncorrelated factors that explained
      78.2% and 74.7% of the variance in nondiabetics (n = 2,760) and diabetics (n =
      399), respectively. These factors were interpreted as 1) weight/waist, 2) blood
      pressure, 3) lipids, and 4) insulin/glucose. Modest differences in the
      associations between fasting insulin and factors 1, 3, and 4 were noted for
      diabetics. These consistently identified composite factors may represent markers
      for underlying pathophysiologic mechanisms of the insulin resistance syndrome and
      risk of non-insulin-dependent diabetes mellitus.

PMID- 9525531
TI  - Prevalence and risk factors for diabetic retinopathy in the multiethnic
      population of Mauritius.
AB  - This study examines the prevalence of, and risk factors for, diabetic retinopathy
      in Asian Indian, Chinese, and Creole Mauritians in whom there is an increasing
      prevalence of non-insulin-dependent diabetes mellitus (NIDDM). As part of a
      population-based survey on the Indian Ocean island of Mauritius in 1992, glucose
      tolerance was classified using a 75-g oral glucose tolerance test on 6,553
      persons. Subjects with newly diagnosed (n = 358) or known diabetes (n = 388), and
      a random sample of one in four subjects with impaired glucose tolerance (n =
      165), had stereoscopic 45 degrees retinal photographs taken of three fields in
      the right eye after mydriasis. Photographs were graded according to a modified
      version of the Airlie House criteria. The prevalence of nonproliferative and
      proliferative retinopathy was: 14.5% and 0.3%, respectively, in newly diagnosed
      diabetic subjects; 42.0% and 2.3%, respectively, in known diabetic subjects; and
      9.1% and 0%, respectively, in persons with impaired glucose tolerance. Muslim
      Indians had the lowest prevalence of retinopathy (10.8% and 34.0% for new and
      known diabetes, respectively), but after adjusting for other factors, this was
      significantly different only to Creoles (18.8% and 53.8%, respectively).
      Univariate analysis revealed significant differences between diabetic subjects
      with and without retinopathy in mean age, body mass index, fasting and 2-hour
      plasma glucose levels, systolic and diastolic blood pressure, fasting
      triglycerides, serum creatinine, and urinary albumin levels. For known diabetes,
      mean duration of diabetes and the proportion using insulin were also greater in
      those with retinopathy. Multivariate analysis using logistic regression confirmed
      that increasing duration of diabetes, fasting plasma glucose, systolic blood
      pressure, and urinary albumin concentration, and decreasing body mass index, were
      independently associated with retinopathy. The high prevalence of diabetic
      retinopathy observed in all major ethnic groups in Mauritius portends a serious
      public health problem, given the relative recency of the NIDDM epidemic in that
      country and the limited resources for laser photocoagulation. Strategies to
      minimize this problem among those already known to have diabetes should include
      strict control of plasma glucose and blood pressure.

PMID- 9525532
TI  - Calcitropic hormones and occupational lead exposure.
AB  - The authors sought to clarify in a cross-sectional study the possible
      associations between homeostatic regulators of calcium and occupational exposure
      to lead. Subjects were 146 industrial male employees, 56 with and 90 without
      occupational lead exposure. The main outcome measures were serum concentration of
      parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D (calcitriol). The median
      values of blood lead were 40.5 microg/dl in the exposed group and 4.0 microg/dl
      in the controls. There were no differences between groups in dietary history and
      serum calcium levels. PTH and calcitriol levels were significantly higher in the
      exposed than in the nonexposed subjects (42.0+/-24.2 vs. 33.6+/-14.9 pg/ml, p
      <0.05; and 83.8+/-27.0 vs. 67.9+/-17.6 pmol/liter, p <0.001, respectively).
      Multivariate analyses showed that after controlling for possible confounders,
      occupational lead exposure (no/yes) was independently associated with PTH level
      (pg/ml) (beta = 7.81, 95% confidence interval (CI) 3.7-11.5) and with calcitriol
      (pmol/liter) (beta = 12.3, 95% CI 3.84-20.8). It is concluded that subjects
      occupationally exposed to lead show a substantial compensatory increase in PTH
      and calcitriol activities which keep serum calcium levels within normal range.
      This may be of clinical significance since a sustained increase in calcitropic
      hormones in susceptible subjects may eventually increase the risk of bone
      disorders.

PMID- 9525533
TI  - Use of neural networks to model complex immunogenetic associations of disease:
      human leukocyte antigen impact on the progression of human immunodeficiency virus
      infection.
AB  - Complex immunogenetic associations of disease involving a large number of gene
      products are difficult to evaluate with traditional statistical methods and may
      require complex modeling. The authors evaluated the performance of feed-forward
      backpropagation neural networks in predicting rapid progression to acquired
      immunodeficiency syndrome (AIDS) for patients with human immunodeficiency virus
      (HIV) infection on the basis of major histocompatibility complex variables.
      Networks were trained on data from patients from the Multicenter AIDS Cohort
      Study (n = 139) and then validated on patients from the DC Gay cohort (n = 102).
      The outcome of interest was rapid disease progression, defined as progression to
      AIDS in <6 years from seroconversion. Human leukocyte antigen (HLA) variables
      were selected as network inputs with multivariate regression and a previously
      described algorithm selecting markers with extreme point estimates for
      progression risk. Network performance was compared with that of logistic
      regression. Networks with 15 HLA inputs and a single hidden layer of five nodes
      achieved a sensitivity of 87.5% and specificity of 95.6% in the training set, vs.
      77.0% and 76.9%, respectively, achieved by logistic regression. When validated on
      the DC Gay cohort, networks averaged a sensitivity of 59.1% and specificity of
      74.3%, vs. 53.1% and 61.4%, respectively, for logistic regression. Neural
      networks offer further support to the notion that HIV disease progression may be
      dependent on complex interactions between different class I and class II alleles
      and transporters associated with antigen processing variants. The effect in the
      current models is of moderate magnitude, and more data as well as other host and
      pathogen variables may need to be considered to improve the performance of the
      models. Artificial intelligence methods may complement linear statistical methods
      for evaluating immunogenetic associations of disease.

PMID- 9525534
TI  - Residential setting as a risk factor for Lyme disease in a hyperendemic region.
AB  - The hypothesis that residence in a uniform medium-density residential development
      is associated with lower incidence of Lyme disease is tested with data from a
      rural, 12-town region of south-central Connecticut where the disease is
      hyperendemic. The residential setting for 424 cases identified by active
      surveillance from 1993 through 1995 was determined. Cases located within the
      Eastern Coastal ecologic region, where tick densities are known to be higher than
      inland and where most of the population in the region resides, were selected for
      further analysis. Within this region, residence in a homogeneous area of medium
      density development at least 30 acres (12 ha) in size was associated with a two-
      to 10-fold lower level of risk than residence in surrounding less developed
      areas, depending on the estimate of residential population. Type of residential
      development may be an important factor to consider, in addition to other
      environmental variables, in studies of peridomestic vector-borne disease in human
      populations.

PMID- 9525536
TI  - Cancer of the nasal cavity and paranasal sinuses and exposure to environmental
      tobacco smoke in pet dogs.
AB  - A case-control study of nasal cancer in pet dogs was conducted to test the
      hypothesis that exposure to environmental tobacco smoke increases risk. Cases (n
      = 103) were selected from a teaching hospital during 1986-1990. Controls (n =
      378) with other forms of cancer were selected from the same study base. Exposure
      to environmental tobacco smoke was evaluated by determining the number of smokers
      in the household, the packs of cigarettes smoked per day at home by each smoker,
      the number of years that each person smoked during the dog's lifetime, and the
      proportion of time spent indoors by the dog. The crude odds ratio for exposure to
      environmental tobacco smoke was 1.1 (95% confidence interval (CI) 0.7-1.8) and
      was unchanged after adjustment for confounders. Skull shape was found to exert a
      pronounced modifying effect; among dolichocephalic (long-nosed) dogs, the odds
      ratio for a smoker in the house was 2.0 (95% CI 1.0-4.1). A monotonic increase in
      the odds ratios across strata of total packs smoked and total indoor exposure to
      environmental tobacco smoke was found in this group of dogs, with risks of
      approximately 2.5 for the highest stratum. Conversely, all odds ratios for
      exposure to environmental tobacco smoke among short- and medium-length-nosed dogs
      were approximately 0.5. The data support an association between environmental
      tobacco smoke and canine nasal cancer.

PMID- 9525535
TI  - Risk factors for horizontal transmission of hepatitis B virus in a rural district
      in Ghana.
AB  - Most hepatitis B virus (HBV) infections in sub-Saharan African infants and
      children are acquired through horizontal transmission, but the exact mechanisms
      of spread have not been documented. The authors conducted a study in rural Ghana
      which determined seroprevalence in a probability sample of 1,385 individuals of
      all ages, and evaluated risk factors for horizontal transmission of HBV in a
      subsample of 547 children aged 1-16 years who were not hepatitis B surface
      antigen (HBsAg) carriers. Most residents in this district live in compounds which
      typically contain 2-4 households each. Overall prevalence of HBV seropositives
      (any HBV marker) was 74.7% (95% confidence interval (CI) 72.5%-76.9%). Prevalence
      of HBsAg was 20.9% (95% CI 18.8%-23.1%). The data suggest a continuous nonuniform
      acquisition of HBV infection with advancing age predominantly through horizontal
      transmission in childhood, with the household, rather than the domestic compound,
      being the primary place for transmission. The behaviors most strongly associated
      with prevalence of HBV were sharing of bath towels (OR = 3.1, 95% CI 2.1-4.5),
      sharing of chewing gum or partially eaten candies (OR = 3.4, 95% CI 2.3-5.0),
      sharing of dental cleaning materials (OR = 2.5, 95% CI 1.3-4.6), and biting of
      fingernails in conjunction with scratching the backs of carriers (OR = 2.5, 95%
      CI 1.6-4.3).

PMID- 9525537
TI  - Polychlorinated biphenyls in blood plasma among Swedish female fish consumers in
      relation to low birth weight.
AB  - The authors examined the hypothesized association between the body burden of
      polychlorinated biphenyls (PCB) in women and the risk of low birth weight for
      their infants. In Sweden, a main exposure route for PCBs and other persistent
      organochlorine compounds is through the consumption of fatty fish from the Baltic
      Sea (on the Swedish east coast). A previous comparison between a cohort of
      consumers of large quantities of fish from the Swedish east coast and a reference
      population, together with a following analysis based on questionnaire data from a
      case-control study within the east coast cohort, supported the hypothesized
      association. In 1995, blood samples were collected from the wives and ex-wives of
      fishermen from the Swedish east coast (n = 192) who had given birth during the
      period 1973-1991. Cases (n = 57), i.e., infants with low birth weight (1,500
      2,750 g), were matched with controls (n = 135; birth weight, 3,250-4,500 g) on
      gender, parity, and calendar year of birth. The concentration of 2,2',4,4',5,5'
      hexachlorobiphenyl (CB-153) in plasma was analyzed; it has been suggested that CB
      153 is a relevant biomarker of exposure to PCBs. The concentration of CB-153 in
      the plasma of mothers during the year of childbirth was "estimated" using some
      alternative plausible kinetic models. For two alternative estimated exposure
      datasets, which were focused on separately, an increase in the risk of a low
      birth weight was observed at a CB-153 concentration of 300 and 400 ng/g lipid
      weight, respectively (adjusted odds ratios of 2.1 (95% confidence interval (CI)
      1.0-4.7) and 2.3 (95% CI 0.9-5.9)). The present results strengthen the findings
      reported previously for this study population.

PMID- 9525538
TI  - Rate of caffeine metabolism and risk of spontaneous abortion.
AB  - In a case-control study of 73 women with and 141 women without spontaneous
      abortion, the authors determined the activity of the three principal caffeine
      metabolizing enzymes--cytochrome P-4501A2 (CYP1A2), xanthine oxidase, and N
      acetyltransferase 2--by measuring levels of caffeine metabolites in urine. After
      examining the effect of enzyme activity and different levels of caffeine intake,
      they concluded that there was no evidence that an interaction between enzyme
      activity and caffeine intake during pregnancy resulted in risk of spontaneous
      abortion. In a subsample comparing 24 cases with recurrent (two or more)
      spontaneous abortions and 21 controls with two or more livebirths and no previous
      spontaneous abortions, the unadjusted odds ratio for low CYP1A2 enzyme activity
      (below the median) was 0.92 (95% confidence interval (CI) 0.28-3.04) compared
      with higher CYP1A2 activity. The odds ratio for risk of recurrent spontaneous
      abortion and low xanthine oxidase activity (below the median) versus higher
      activity was 0.37 (95% CI 0.10-1.29). Phenotypically slow acetylators (N
      acetyltransferase 2 index <0.37) had an odds ratio of 1.58 (95% CI 0.48-5.13) for
      recurrent loss compared with rapid acetylators. Thus, some association of the
      latter two caffeine-metabolizing enzymes with recurrent spontaneous abortion is
      suggested but may also be due to chance.

PMID- 9525539
TI  - Re: "Heart rate variability from short electrographic recordings predicts
      mortality from all causes in middle-aged and elderly men: the Zutphen Study".

PMID- 9525540
TI  - Re: "p53 protein overexpression in relation to risk factors for breast cancer".

PMID- 9525541
TI  - Anticoagulation in dilated cardiomyopathy.
AB  - Patients with dilated cardiomyopathy have multiple factors that predispose to
      thromboembolic events. However, reports of the incidence of thromboembolic events
      in this population vary widely. There has never been a controlled study of long
      term anticoagulation among patients with congestive heart failure due to dilated
      cardiomyopathy. In this report we review the available published data regarding
      the risk of thromboembolic events in patients with dilated cardiomyopathy, and
      the effectiveness and risks of anticoagulation in this population. Although many
      investigators have called for a prospective, randomized clinical trial to assess
      the risks and benefits of long-term anticoagulation in patients with dilated
      cardiomyopathy, a more practical approach may be to compile a national registry
      of patients with dilated cardiomyopathy to collect observational data on both the
      rate of embolic events as well as bleeding complications among patients with and
      without anticoagulation.

PMID- 9525542
TI  - Warfarin anticoagulation and survival: a cohort analysis from the Studies of Left
      Ventricular Dysfunction.
AB  - OBJECTIVES: We sought to evaluate the relation between warfarin anticoagulation
      and survival and morbidity from cardiac disease in patients with left ventricular
      (LV) dysfunction. BACKGROUND: Warfarin anticoagulation plays a major role in the
      management of patients who have had a large myocardial infarction and in those
      with atrial fibrillation. However, its use in patients with LV systolic
      dysfunction has been controversial. METHODS: We reviewed data on warfarin use in
      6,797 patients enrolled in the Studies of Left Ventricular Dysfunction (SOLVD)
      trial and analyzed the relation between warfarin use and all-cause mortality, as
      well as the combined end point of death or hospital admission for heart failure.
      We used Cox regression to adjust for differences in baseline characteristics and
      to test for the interaction between warfarin use and selected patient variables
      in relation to outcome. RESULTS: On multivariate analysis, use of warfarin was
      associated with a significant reduction in all-cause mortality (adjusted hazard
      ratio [HR] 0.76, 95% confidence interval [CI] 0.65 to 0.89, p = 0.0006) and in
      the risk of death or hospital admission for heart failure (HR 0.82, 95% CI 0.72
      to 0.93, p = 0.0002). Risk reduction was observed when each trial or
      randomization arm was analyzed separately, as well as in both genders. It was not
      significantly influenced by the presence of atrial fibrillation, age, ejection
      fraction, New York Heart Association functional class or etiology. CONCLUSIONS:
      In patients with LV systolic dysfunction, warfarin use is associated with
      improved survival and reduced morbidity. This association is primarily due to a
      reduction in cardiac events and does not appear to be limited to any particular
      subgroup.

PMID- 9525543
TI  - Expression of atrial and brain natriuretic peptides and their genes in hearts of
      patients with cardiac amyloidosis.
AB  - OBJECTIVES: We investigated the expression of atrial natriuretic peptide (ANP)
      and brain natriuretic peptide (BNP) and their genes in the hearts of patients
      with cardiac amyloidosis and those with isolated atrial amyloidosis. BACKGROUND:
      The expression of ANP and BNP is augmented in the ventricles of failing or
      hypertrophied hearts, or both. The expression of ANP and BNP in the ventricles of
      hearts with cardiac amyloidosis, which is hemodynamically similar to restrictive
      cardiomyopathy, is not yet known. ANP is the precursor protein of isolated atrial
      amyloid. METHODS: We analyzed the immunohistocytochemical localizations of ANP
      and BNP as well as the expression of their mRNAs by in situ hybridization in the
      myocardium and measured the plasma levels of ANP and BNP in patients with cardiac
      amyloidosis. RESULTS: Four of the five right and all six left ventricular
      endomyocardial biopsy specimens obtained from six patients with cardiac
      amyloidosis were immunohistochemically positive for both ANP and BNP; none of the
      biopsy specimens from eight normal subjects were positive for ANP or BNP. All
      four of the right atria obtained at operation showed positive immunoreactions for
      both peptides. Electron microscopy identified specific secretory granules in
      ventricular myocytes of the patients with cardiac amyloidosis, but not in
      ventricular myocytes from the normal control subjects. Double immunocytochemical
      analysis revealed the co-localization of ANP and BNP in the same granules and
      that isolated atrial amyloid fibrils were immunoreactive for ANP and BNP, whereas
      ventricular amyloid fibrils were negative for both peptides. Both ANP mRNA and
      BNP mRNA were expressed in the ventricles of the patients with cardiac
      amyloidosis but not in the normal ventricles. The autopsy study of four patients
      with cardiac amyloidosis revealed an almost transmural distribution of ANP and
      BNP, with predominance in the endocardial side. Plasma BNP levels in the patients
      were markedly elevated ([mean +/- SD] 1,165.1+/-561.2 pg/ml) compared with those
      in the control subjects (8.9+/-6.0 pg/ml, p < 0.05). CONCLUSIONS: Expression of
      ANP and BNP and their genes was augmented in the ventricular myocytes of the
      patients with cardiac amyloidosis. Both regional mechanical stress by amyloid
      deposits and hemodynamic stress by diastolic dysfunction may be responsible for
      the expression of the peptides in patients with cardiac amyloidosis.

PMID- 9525544
TI  - Peak exercise oxygen consumption in chronic heart failure: toward efficient use
      in the individual patient.
AB  - OBJECTIVES: This study sought to 1) assess the short-, medium-and long-term
      prognostic power of peak oxygen consumption (VO2) in patients with heart failure;
      2) verify the consistency of a nonmeasurable anaerobic threshold (AT) as a
      criterion of nonapplicability of peak VO2; 3) develop simple rules for the
      efficient use of peak VO2 in individualized prognostic stratification and
      clinical decision making. BACKGROUND: Peak VO2, when AT is identified, is among
      the indicators for heart transplant eligibility. However, in clinical practice
      the application of defined peak VO2 cutoff values to all patients could be
      inappropriate and misleading. METHODS: Six hundred fifty-three patients
      consecutively considered for eligibility for heart transplantation were followed
      up. Outcomes (cardiac death and urgent transplantation) were determined when all
      survivors had a minimum of 6 months of follow-up. RESULTS: Contraindication to
      the exercise test identified very high risk patients. The relatively small sample
      of women did not allow inferences to be drawn. In men, peak VO2 stratified into
      three levels (< or = 10, 10 to 18 and >18 ml/kg per min) identified groups at
      high, medium and low risk, respectively. The prognostic power of peak VO2 < or =
      10 ml/kg per min was maintained even when the AT was not detected. In patients in
      New York Heart Association functional class III or IV, peak VO2 did not have
      prognostic power. In patients in functional class I or II, peak VO2
      stratification was prognostically valuable, but less so at 6 than at 12 or 24
      months. Age did not influence peak VO2 prognostic stratification. CONCLUSIONS: A
      contraindication to exercise testing should be considered a priority for listing
      patients for heart transplantation. Only in less symptomatic male patients does a
      peak VO2 < or = 10 ml/kg per min identify short-, medium- and long-term high risk
      groups. A peak VO2 >18 ml/kg per min implies good prognosis with medical therapy.

PMID- 9525546
TI  - Is time running out on streptokinase?

PMID- 9525545
TI  - Efficacy of streptokinase, but not tissue-type plasminogen activator, in
      achieving 90-minute patency after thrombolysis for acute myocardial infarction
      decreases with time to treatment. PERM Study Group. Prospective Evaluation of
      Reperfusion Markers.
AB  - OBJECTIVES: We sought to examine the relation between time to treatment and 90
      min patency rates in patients receiving intravenous streptokinase (SK) or
      accelerated tissue-type plasminogen activator (t-PA). BACKGROUND: Early patency
      of the infarct-related artery is a major determinant of survival after
      thrombolysis for acute myocardial infarction. Some data suggest that time to
      treatment may influence the efficacy of nonfibrin-specific thrombolytic agents in
      restoring early patency of the infarct-related vessel. METHODS: We performed a
      retrospective analysis of a cohort of 481 patients receiving thrombolytic therapy
      for acute myocardial infarction <6 h after pain onset, all of whom underwent 90
      min coronary angiography. Patency of the infarct-related artery was graded by two
      observers who had no knowledge of the treatment received or the time between pain
      and therapy. RESULTS: There was no difference in baseline clinical or
      angiographic characteristics according to the timing or nature of treatment.
      Thrombolysis in Myocardial Infarction (TIMI) flow grade 2 or 3 patency rate after
      SK correlated negatively with the time between onset of pain and thrombolysis (r
      = 0.8, p = 0.05), whereas the 90-min patency rate after t-PA appeared stable as a
      function of time to treatment. When patients were categorized as having received
      treatment <3 or > or = 3 h after pain onset, the patency rate was similar with t
      PA, but significantly higher when SK was administered early rather than late,
      regardless of whether TIMI flow grades 2 and 3 were pooled (86.9% vs. 59.4%, p =
      0.0001) or TIMI flow grade 3 alone was considered to indicate patency (81.7% vs.
      53.6%, p = 0.0001). Multivariate logistic regression analysis showed a negative
      effect of time to treatment on the patency probability for SK (p = 0.0001) but
      not for t-PA. CONCLUSIONS: The efficacy of streptokinase but not t-PA in
      restoring early coronary patency after intravenous thrombolysis is markedly lower
      when patients are treated later after onset of pain.

PMID- 9525547
TI  - Prognostic significance of ST segment shift early after resolution of ST
      elevation in patients with myocardial infarction treated with thrombolytic
      therapy: the GUSTO-I ST Segment Monitoring Substudy.
AB  - OBJECTIVES: We sought to study the relation between recurrent ST segment shift
      within 6 to 24 h of initial resolution of ST elevation after thrombolytic therapy
      and 30-day and 1-year mortality. BACKGROUND: Rapid and stable resolution of ST
      segment elevation in relation to thrombolytic therapy in patients with an acute
      myocardial infarction is an indicator of culprit artery patency. Whether
      recurrence of ST segment shift during continuous ST monitoring after initial
      resolution is related to poor prognosis has not been studied. METHODS: ST segment
      monitoring was performed within 30 min after thrombolytic therapy for acute
      myocardial infarction. The predictive value of a new ST segment shift (assessed
      as > or = 0.1-mV deviation from the baseline) 6 to 24 h after thrombolytic
      therapy was studied with respect to 30-day and 1-year mortality. RESULTS: Of 734
      patients, 243 had a new ST segment shift (33%). The 30-day mortality rate in
      patients with an ST shift (7.8%) was significantly higher than that in patients
      without an ST shift (2.25%, p = 0.001), as was the 1-year mortality rate (10.3%
      vs. 5.7%, respectively, p = 0.025). Multivariable analysis revealed an
      independent predictive value of ST shift with respect to 30-day mortality (p =
      0.008), even after consideration of multiple clinical risk factors in the overall
      Global Utilization of Streptokinase and TPA for Occluded Coronary Arteries
      (GUSTO)-I mortality model (p = 0.0001). Moreover, the duration of the ST shift
      bore a direct relation with 1-year mortality (p = 0.008). CONCLUSIONS: Detection
      of ST segment shift early after thrombolytic therapy for acute myocardial
      infarction is a simple, noninvasive means of identifying patients at high risk
      and is superior to other commonly assessed clinical risk factors. Thus, patients
      with a new ST shift after the first 6 h, but within 24 h, represent a high risk
      group that may benefit from more aggressive intervention, whereas patients
      without evidence of an ST shift represent a low risk subgroup.

PMID- 9525548
TI  - Angiotensin-converting enzyme genotypes and risk for myocardial infarction in
      women.
AB  - OBJECTIVES: We tested for an association between the angiotensin-converting
      enzyme (ACE) DD polymorphic genotype and myocardial infarction (MI) in a sample
      group composed exclusively of women. BACKGROUND: The human ACE gene occurs with
      either an insertion (I allele) or a deletion (D allele) of a 287-base pair (bp)
      Alu element. Part of the variance in serum ACE levels may be accounted for by
      this polymorphism. Also, the DD genotype has been associated with an increased
      risk of MI in predominantly male populations. However, the risk in women is
      poorly defined. METHODS: Genomic DNA was extracted from buffy coat blood using a
      phenol/chloroform method. Angiotensin-converting enzyme alleles were identified
      using primers to bracket the insertion region in intron 16. Amplification using
      polymerase chain reaction allowed identification of a 490-bp (I allele) or a 190
      bp (D allele) product, or both. RESULTS: Allelic and genotypic frequencies in
      control subjects were similar to those reported in mostly male populations, and
      frequencies of genotypes were in the Hardy-Weinberg equilibrium. In contrast, the
      distribution of genotypes in patients with MI diverged from the equilibrium.
      Specifically, DD genotypic frequency was increased in women with (n = 141) versus
      without (n = 338) a previous MI (39% vs. 29%, odds ratio [OR] 1.54, 95%
      confidence interval 1.02 to 2.32, p < 0.04). Risk was particularly increased in
      women <60 years old (OR 2.04, p < 0.05). In contrast, the DD genotype did not
      predict angiographic coronary artery disease. CONCLUSIONS: Consistent with
      findings in male-dominated populations, a modest association of the ACE DD
      genotype with MI was found in women. The basis for this association requires
      further study.

PMID- 9525549
TI  - Case-control study of passive smoking at home and risk of acute myocardial
      infarction. Argentine FRICAS Investigators. Factores de Riesgo Coronario en
      America del Sur.
AB  - OBJECTIVES: We sought to study the relation between passive smoking at home and
      the risk of acute myocardial infarction (AMI). BACKGROUND: Previous epidemiologic
      studies have linked environmental tobacco smoke to an increased risk of coronary
      heart disease, but the evidence to support this view is not strong enough. To
      study this issue further, we analyzed the data from a case-control study
      conducted in Argentina between 1991 and 1994. METHODS: Case patients included 336
      never-smokers with AMI. Control patients were 446 never-smokers admitted to the
      same network of hospitals with a wide spectrum of acute disorders unrelated to
      smoking or to known or suspected risk factors for AMI. Data on the smoking habits
      of the participants' close relatives (spouse and children) were collected by
      trained interviewers using a structured questionnaire. RESULTS: Compared with
      subjects whose relatives had never smoked, the multivariate odds ratios for
      passive smokers, according to the smoking status of their relatives, were 1.68
      (95% confidence interval [CI] 1.20 to 2.37) for one or more relatives who smoked;
      1.59 (95% CI 0.85 to 2.96) for a spouse who smoked; 1.24 (95% CI 0.61 to 2.52)
      for a spouse who smoked 1 to 20 cigarettes/day; 4.03 (95% CI 0.99 to 16.32) for a
      spouse who smoked >20 cigarettes/day; and 1.80 (95% CI 1.20 to 2.68) for one or
      more children who smoked. There was a significant interaction between passive
      smoking and hypercholesterolemia (> or = 240 mg/dl), hypertension, diabetes and
      family history of MI. CONCLUSIONS: In never-smokers, passive smoking at home
      appeared to be associated with the risk of AMI, and approximately 14% of cases in
      men and 18% of cases in women in this Argentinian cohort are attributable to
      passive smoking.

PMID- 9525550
TI  - Calcium channel blocking agents and risk of cancer in patients with coronary
      heart disease. Benzafibrate Infarction Prevention (BIP) Study Research Group.
AB  - OBJECTIVES: This analysis sought to estimate the risk ratio for cancer incidence
      and cancer-related mortality associated with the use of calcium channel blocking
      agents (CCBs) in a large group of patients with chronic coronary heart disease
      (CHD). BACKGROUND: Recent publications contend that the use of short-acting CCBs
      may double the risk of cancer incidence and possibly increase mortality in
      hypertensive patients. METHODS: Cancer incidence data were obtained for 11,575
      patients screened for the Bezafibrate Infarction Prevention (BIP) study, one-half
      of whom were treated at the time of screening with CCBs, over a mean follow-up
      period of 2.8 years. Cause-specific mortality was available through September
      1996 (mean follow-up 5.2 years). The statistical power of detecting an odds ratio
      > or = 1.5 (given the cancer incidence rate of 2.1 in the nonusers of CCBs) was
      0.91. The power declined to 0.77, 0.54 and 0.41, with declining odds ratios of
      1.4, 1.3 and 1.25, respectively. RESULTS: Of 246 incident cancer cases, 129
      occurred among the users (2.3%) and 117 among nonusers of CCBs (2.1%). After
      adjustment for age, gender and smoking, the odds ratio estimates for all cancers
      combined was 1.07 (95% confidence interval [CI] 0.83 to 1.37) for CCB users
      relative to nonusers. The adjusted risk ratio for all-cause mortality for age,
      gender and smoking and pertinent prognostic clinical characteristics was
      estimated at 0.94 (95% CI 0.85 to 1.04). The adjusted risk ratio for cancer
      related mortality was 1.03 (95% CI 0.75 to 1.41). CONCLUSIONS: Patients with CHD
      treated with CCBs exhibited a similar risk of cancer incidence and total and
      cancer-related mortality compared with nonusers of CCBs. This analysis provides a
      certain assurance that CCB use in middle-aged and elderly patients with CHD is
      not associated with a meaningful difference in cancer incidence and related
      mortality.

PMID- 9525551
TI  - Do calcium antagonists increase the risk for malignancies?

PMID- 9525552
TI  - Does passive smoking impair endothelium-dependent coronary artery dilation in
      women?
AB  - OBJECTIVES: This study sought to examine whether passive smoking is associated
      with endothelial dysfunction in the coronary arteries. BACKGROUND: Long-term
      exposure to cigarette smoking has been reported to suppress endothelium-dependent
      arterial dilation in humans. Endothelial dysfunction is an early feature of
      atherogenesis, and the impairment of acetylcholine (ACh)-induced coronary artery
      dilation indicates coronary endothelial dysfunction. METHODS: We studied 38 women
      (40 to 60 years old) who had no known risk factors for coronary artery disease
      other than tobacco smoking: 11 nonsmokers who had never smoked and had never been
      regularly exposed to environmental tobacco smoke; 19 passive smokers with self
      reported histories of exposure to environmental tobacco smoke of > or = 1 h/day
      for > or = 10 years; and 8 active smokers. We examined the response of the
      epicardial coronary artery diameters (proximal and distal segments of the left
      anterior descending [LAD] and left circumflex [LCx] coronary arteries) to the
      intracoronary injection of ACh into the left coronary artery by means of
      quantitative coronary angiography. RESULTS: ACh significantly dilated the distal
      segment in nonsmokers (percent change from baseline diameter: LAD 13.7+/-3.4%, p
      < 0.05; LCx 18.8+/-2.9%, p < 0.01) but not the proximal segment (LAD 7.4+/-3.5%;
      LCx 3.1+/-5.0%). ACh significantly constricted all segments of the left coronary
      artery in passive smokers (LAD: proximal -20.3+/-3.7%, p < 0.05; distal -22.3+/
      4.1%, p < 0.01; LCx: proximal -20.8+/-3.1%, p < 0.05; distal -17.3+/-2.9%, p <
      0.01) and active smokers (LAD: proximal -14.8+/-3.4%, p < 0.05; distal -27.2+/
      6.0%, p < 0.01; LCx: proximal -14.5+/-6.6%, p < 0.05; distal -22.4+/-4.0%, p <
      0.01). Thus, ACh constricted most coronary arteries in both passive and active
      smokers and dilated the coronary arteries in nonsmokers. CONCLUSIONS: Impairment
      of ACh-induced coronary artery dilation, indicating coronary endothelial
      dysfunction, may occur diffusely in passive smokers as well as in active smokers.

PMID- 9525553
TI  - Coronary vascular responsiveness to adenosine is impaired additively by blockade
      of nitric oxide synthesis and a sulfonylurea.
AB  - OBJECTIVES: We sought to define effects of glibenclamide, a sulfonylurea known to
      block ATP-dependent potassium (KATP) channels, and Nomega-nitro-L-arginine methyl
      ester (L-NAME), an L-arginine analog known to block nitric oxide (NO) synthesis,
      on coronary vascular responsiveness to adenosine. BACKGROUND: The role of
      adenosine in coronary flow regulation becomes increasingly important when KATP
      channel function or NO synthesis is impaired. Both variables are potentially
      altered in patients with coronary artery disease taking a sulfonylurea. METHODS:
      Dose-response curves relating coronary conductance to plasma adenosine
      concentration were obtained by using intracoronary infusions of adenosine (10 to
      1,000 microg/min) in chronically instrumented dogs. RESULTS: ED50, the plasma
      concentration of adenosine needed to produce 50% of the maximal increase in
      conductance under baseline conditions, increased threefold after either 1 or 10
      mg/kg of L-NAME. ED50 also increased in response to glibenclamide in a dose
      related fashion (5.7-fold increase per 1 mg/kg body weight of glibenclamide).
      Effects of combined blockade of KATP channels and NO synthesis were additive,
      with increases in ED50 as high as 15-fold. Both L-NAME and glibenclamide
      increased systemic pressure and reduced coronary conductance, confirming the
      roles of NO and KATP channels in regulating coronary and systemic vascular tone
      under rest conditions as well as during stress. CONCLUSIONS: Coronary vascular
      responsiveness to adenosine is blunted in vivo by both L-NAME and glibenclamide.
      Effects of the sulfonylurea and blockade of NO synthesis are additive and can
      limit coronary vasodilation as well as other responses involving KATP channels
      and NO.

PMID- 9525554
TI  - Nitric oxide modulation of neutrophil-endothelium interaction: difference between
      arterial and venous coronary bypass grafts.
AB  - OBJECTIVES: This study sought to evaluate the relation between the pattern of
      neutrophil-endothelial adhesion in saphenous vein (SV) and internal mammary
      artery (IMA) grafts and the endothelial production of nitric oxide (NO).
      BACKGROUND: Autologous IMA and SV grafts (SVGs) are increasingly used as conduits
      for coronary bypass grafting. Previous studies have demonstrated a greater
      production of endothelial-derived relaxing factor (NO) from IMA than from SVGs.
      Because of the well known role of NO in modulating the adhesion of
      polymorphonuclear leukocytes to the endothelium, we studied the pattern of
      neutrophil adhesion to the endothelium of IMA and SVs under basal conditions and
      after inhibition of NO synthesis. METHODS: Segments of IMA and SVs were obtained
      from 20 patients undergoing coronary artery bypass graft surgery. We evaluated
      the adhesion of both unstimulated and activated neutrophils to the endothelial
      surface of IMA and SVs in both basal conditions and after inhibition of NO
      synthesis with Nomega-nitro-L-arginine methyl ester. RESULTS: Under basal
      conditions, no difference in unstimulated neutrophil adhesion to endothelium was
      observed between the two vessel conduits. After neutrophil activation, a
      significantly (p < 0.05) greater adhesion of neutrophils was observed in the SV
      than in the IMA. After inhibition of NO release, the adhesion of activated
      neutrophils increased in both vessels, and no significant difference between them
      was observed. The increased adhesion was attenuated by both L-arginine and sodium
      nitroprusside. CONCLUSIONS: The lesser neutrophil adhesion to the endothelium of
      the IMA is a consequence of enhanced release of NO at this level; this effect
      could be responsible for the better early and long-term patency of this conduit
      over the SVG in coronary bypass grafting.

PMID- 9525555
TI  - Endovascular presence of viable Chlamydia pneumoniae is a common phenomenon in
      coronary artery disease.
AB  - OBJECTIVES: We sought to examine coronary arteries for the presence of viable
      bacteria of the fastidious species Chlamydia pneumoniae. BACKGROUND: The
      respiratory pathogen C. pneumoniae has been implicated in the pathogenesis of
      coronary artery disease (CAD). Previous studies have demonstrated an
      antichlamydial seroresponse to be a cardiovascular risk factor and coronary
      atheromata to contain chlamydial components in varying proportions. Endovascular
      demonstration of replicating bacteria is required to provide evidence for an
      infectious component in CAD and a rationale to discuss antimicrobial therapy.
      METHODS: Myocardial revascularization was performed in 70 patients.
      Atherosclerotic lesions from 53 coronary endarterectomy and 17 restenotic bypass
      samples were cultured and subjected to nested polymerase chain reaction (PCR) for
      C. pneumoniae. Antichlamydial immunoglobulin G (IgG), IgA and IgM was examined by
      microimmunofluorescence. RESULTS: Viable C. pneumoniae was recovered from 11
      (16%) of 70 atheromata, and chlamydial deoxyribonucleic acid (DNA) was detected
      in 21 (30%) of 70 atheromata; 17 nonatherosclerotic control samples were PCR
      negative (p < 0.01). Fifteen (28%) of 53 endarterectomy and 6 (35%) of 17 bypass
      samples were PCR-positive. DNA sequencing of six different PCR products did not
      reveal differences between coronary isolates and respiratory reference strains,
      suggesting that common respiratory strains gain access to the systemic
      circulation. Serologic results did not correlate with direct detection results
      and did not identify individual endovascular infection. CONCLUSIONS: A
      significant proportion of atherosclerotic coronary arteries harbor viable C.
      pneumoniae. This finding supports the hypothesis of a chlamydial contribution to
      atherogenesis. Whether chlamydiae initiate atherosclerotic injury, facilitate its
      progression or colonize atheromata is unknown. However, the endovascular presence
      of viable bacteria justifies a controlled clinical investigation of antimicrobial
      treatment benefit in the therapy and prevention of CAD.

PMID- 9525556
TI  - Evaluation of coronary flow velocity dynamics and flow reserve in patients with
      Kawasaki disease by means of a Doppler guide wire.
AB  - OBJECTIVES: To assess the pathophysiologic effects of the coronary sequelae of
      Kawasaki disease on coronary hemodynamic variables, we regionally evaluated the
      flow velocity dynamics and flow reserve in coronary vessels with lesions using an
      intracoronary Doppler flow guide wire. BACKGROUND: The pathophysiologic effects
      of the coronary sequelae of Kawasaki disease on coronary hemodynamic variables
      have not been completely clarified, and we previously reported some discrepancies
      between coronary angiographic findings and exercise stress tests in Kawasaki
      disease. METHODS: Doppler phasic coronary flow velocity was determined using an
      0.018-in. (0.046-cm) intracoronary Doppler flow guide wire at rest and during the
      adenosine triphosphate-induced hyperemic response in 95 patients (75 male, 20
      female, mean age 9.8+/-6.2 years) with Kawasaki disease. RESULTS: In 25 patients
      with coronary aneurysms in 29 vessels, the average peak velocity and diastolic to
      systolic velocity ratio were significantly (p < 0.05) decreased in the moderate
      sized and large-sized aneurysms. Significantly lower values in coronary flow
      reserve (CFR) were noted in 3 of 10 vessels with moderate aneurysms and in 4 of 7
      vessels with large aneurysms. A significant positive correlation (y = 0.53x +
      14.6, r2 = 0.91) was observed between the percent diameter stenosis evaluated by
      angiography and that calculated from the flow velocity measurement. However, the
      percent diameter stenosis calculated from the flow velocity measurement was
      underestimated compared with that determined by angiography in the stenotic
      lesions of intermediate severity. A reduced CFR was noted in five of seven
      vessels with intermediate stenosis ranging from 50% to 75%, and also in three
      vessels with mild stenosis ranging from 30% to 40%. A reduced CFR was also
      observed in six of the eight angiographically normal vessels associated with the
      area of reduced perfusion on exercise thallium-201 myocardial scintigraphy.
      CONCLUSIONS: Abnormalities in flow dynamics and a reduction in flow reserve were
      revealed in coronary aneurysms of intermediate to large size and in stenotic
      lesions, even of mild to intermediate severity, in patients with Kawasaki
      disease. Abnormalities in the coronary microcirculation, as well as epicardial
      lesions, contribute to the pathophysiologic responses in Kawasaki disease.

PMID- 9525557
TI  - Long-term follow-up after deferral of percutaneous transluminal coronary
      angioplasty of intermediate stenosis on the basis of coronary pressure
      measurement.
AB  - OBJECTIVES: This study sought to determine the safety of deferral of percutaneous
      transluminal coronary angioplasty (PTCA) of angiographically intermediate but
      functionally nonsignificant stenosis, as assessed by coronary pressure
      measurement and myocardial fractional flow reserve (FFRmyo). BACKGROUND: Decision
      making in patients with chest pain and intermediate coronary stenosis remains
      difficult. In these cases it is unclear whether the risk of an intervention and
      the potentially subsequent restenosis outweigh the future risk of an event if the
      lesion remains untreated. FFRmyo is a lesion-specific functional index of
      epicardial stenosis severity that accurately distinguishes stenoses associated
      with inducible ischemia. METHODS: Retrospective analysis and follow-up was
      performed in 100 consecutive patients referred to our centers for PTCA of an
      intermediate stenosis but in whom the planned intervention was deferred on the
      basis of an FFRmyo > or = 0.75. RESULTS: During a follow-up period of 18+/-13
      months (mean +/- SD, range 3 to 42), two patients died of noncardiac causes.
      Ninety patients remained free of any coronary events, and their average Canadian
      Cardiovascular Society class decreased from 2.0+/-1.2 at baseline to 0.7+/-0.9 at
      follow-up (p < 0.0001). A coronary event occurred in eight patients and was
      target-vessel related in four. CONCLUSIONS: In patients with chest pain referred
      for PTCA of an intermediate stenosis, deferral of the intervention on the basis
      of an FFRmyo > or = 0.75 is safe and is associated with a much lower clinical
      event rate than if the procedure had been performed as initially planned in these
      patients.

PMID- 9525558
TI  - Prognostic value of exercise thallium-201 imaging performed within 2 years of
      coronary artery bypass graft surgery.
AB  - OBJECTIVES: We sought to determine the prognostic capabilities of exercise
      thallium (Tl)-201 tomographic imaging performed relatively early (within 2 years)
      after coronary artery bypass graft surgery (CABG). BACKGROUND: Exercise testing
      is commonly performed after CABG, but few data exist demonstrating its prognostic
      value in this setting. METHODS: Four hundred eleven patients were followed up for
      a median duration of 5.8 years. Eleven prospectively chosen clinical, exercise
      and Tl-201 variables were tested for their associations with outcome end points
      by means of proportional hazards regression models. RESULTS: During follow-up
      there were 60 deaths from any cause, 53 initial cardiac deaths or nonfatal
      myocardial infarctions (MIs) and 22 late (>3 months after the Tl-201 study)
      revascularization procedures. The number of abnormal Tl-201 segments on the
      postexercise image was the only variable in the multivariate analyses to show a
      significant association with all three outcome end points: chi-square 7.3, p =
      0.007 for overall mortality; chi-square 8.1, p = 0.004 for cardiac death or MI;
      chi-square 7.8, p = 0.005 for any cardiac event. Other independent predictors of
      outcome were exercise duration (chi-square 10.7, p = 0.001) and age (chi-square
      3.9, p = 0.049) for overall mortality and exercise angina score (chi-square 8.7,
      p = 0.003) for cardiac death or MI. The 5-year survival rate free of cardiac
      death or MI was 93% for patients without angina and a normal image or small
      postexercise perfusion defect versus 71% for patients with angina and a medium or
      large defect. CONCLUSIONS: Exercise Tl-201 imaging performed within 2 years of
      CABG can stratify patients into low and high risk subgroups.

PMID- 9525559
TI  - Clinical and electrophysiologic characteristics and long-term efficacy of slow
      pathway catheter ablation in patients with spontaneous supraventricular
      tachycardia and dual atrioventricular node pathways without inducible
      tachycardia.
AB  - OBJECTIVES: We sought to investigate the long-term efficacy of slow-pathway
      catheter ablation in patients with spontaneous, documented paroxysmal
      supraventricular tachycardia (PSVT) and dual atrioventricular (AV) node pathways
      but without inducible tachycardia. BACKGROUND: The lack of reproduction of
      clinical PSVT by programmed electrical stimulation, which is not uncommon in AV
      node reentrant tachycardia (AVNRT), is a dilemma in making the decision of the
      therapeutic end point of radiofrequency catheter ablation. METHODS: Twenty-seven
      patients (group A) with documented but noninducible PSVT and with dual AV node
      pathways were prospectively studied. Programmed electrical stimulation could
      induce a single AV node echo beat in 12 patients, double echo beats in 4 patients
      and none in 11 patients at baseline or during isoproterenol infusion. Of the
      patients in group A, 16 underwent slow-pathway catheter ablation and 11 did not.
      The clinical and electrophysiologic characteristics of the 27 patients were
      compared with those of patients with dual AV node pathways and inducible AVNRT
      (group B, n = 55) and patients with dual AV node pathways alone without clinical
      PSVT (group C, n = 47). RESULTS: During 23+/-13 months of follow-up, none of the
      16 patients with slow-pathway catheter ablation had recurrence of PSVT. However,
      7 of the 11 patients without ablation had PSVT recurrence at 13+/-14 months of
      follow-up (p < 0.03 by Kaplan-Meier analysis). Compared with groups B and C,
      group A consisted predominantly of men who had better retrograde AV node
      conduction and a narrower zone for anterograde slow-pathway conduction.
      CONCLUSIONS: Slow-pathway catheter ablation is highly effective in eliminating
      spontaneous PSVT in which the tachycardia is not inducible despite the presence
      of dual AV node pathways.

PMID- 9525560
TI  - Assessment of left ventricular contractile state by preload-adjusted maximal
      power using echocardiographic automated border detection.
AB  - OBJECTIVES: We sought to assess the ability of preload-adjusted maximal power
      measured by echocardiographic automated border detection (ABD) to quantify left
      ventricular (LV) contractility by determining the effects of alterations in
      preload, afterload and contractile state. BACKGROUND: Preload-adjusted maximal
      power can reflect LV contractile state relatively independent of changes in
      loading conditions. METHODS: Eight anesthetized dogs had placement of aortic
      electromagnetic flow probes, LV and arterial pressure catheters and inferior vena
      caval (IVC) occluders; four had placement of thoracic aortic balloon occluders.
      Echocardiographic ABD measures of cross-sectional area were used as a surrogate
      for LV volume, and flow was estimated as the first derivative of area with
      respect to time. Power was calculated as the product of flow and pressure.
      RESULTS: Preload independence during vena caval occlusions was achieved by
      preload adjustment (1/[end-diastolic area]3/2). Afterload independence was
      demonstrated by preload-adjusted maximal power being unaffected by acute
      increases in LV systolic pressure induced by aortic occlusion. ABD preload
      adjusted maximal power reflected changes in contractile state: increasing with
      dobutamine infusion from 36+/-14 to 70+/-15 mW/cm4 (p < 0.05 vs. control) and
      decreasing with propranolol infusion from 35+/-13 to 17+/-7 mW/cm4 (p < 0.05 vs.
      control). These changes were significantly correlated with calculations of
      preload-adjusted maximal power using aortic flow (r = 0.90, SEE 10.5 mW/cm4) and
      load-independent measures of end-systolic elastance from pressure-area loops (r =
      0.90, SEE 10.6 mW/cm4). Calculations of normalized preload-adjusted maximal power
      using arterial pressure were also closely correlated with similar calculations
      using LV pressure (r = 0.99, SEE 3%). CONCLUSIONS: Preload-adjusted maximal power
      using echocardiographic ABD can predict LV contractile state relatively
      independent of loading conditions and has potential for clinical application.

PMID- 9525561
TI  - Progress in developing a noninvasive load-independent marker of ventricular
      contractility.

PMID- 9525562
TI  - Panoramic coronary angiography.
AB  - OBJECTIVES: We describe a new imaging technique for coronary angiography.
      BACKGROUND: The conventional approach to coronary angiography exploits static
      perspective imaging over multiple cardiac cycles, using a limited number of
      empirically selected views. This approach entails both lack and redundancy of
      information and may result in suboptimal visualization of the individual lesion,
      contributing to diagnostic inaccuracy. METHODS: We developed a new imaging
      technique exploiting dynamic perspective, obtained by transverse 180 degree
      rotation of the C arm of a conventional angiographic unit during standard
      selective coronary opacification and filming. This technique yields a picture of
      the coronary tree isocentrically rotating around the longitudinal axis and
      conveying complete three-dimensional information. RESULTS: A complete diagnostic
      run for both coronary arteries, including two 25 degree cranial and two 25 degree
      caudal scans is accomplished with a total cine time of 16 s and 45 ml of contrast
      medium, about half of that required by conventional angiography. In a series of
      129 consecutive patients studied by both the conventional and the new technique
      with quantitative measurements of the severity of the stenoses, the final
      diagnosis was identical in 65. In no case was a stenosis detected only by the
      conventional approach. However, in 31 patients the new technique permitted
      identification of 34 critical stenoses (79+/-8% [mean +/- SD]) either
      underestimated (61+/-3% n = 24, p < 0.001) or undetected (21+/-22%, n = 10, p <
      0.001) in the standard projections. In a further 28 cases, 33 subcritical lesions
      (60+/-5%) were visualized in the rotational images but were insignificant (24+/
      22% p < 0.001) in the standard projections. In five additional patients, distinct
      laminar plaques were clearly visualized only by the panoramic approach.
      CONCLUSIONS: This new technique can be easily implemented on conventional
      angiographic equipment at no additional cost. It provides complete, operator
      independent exploitation of the angiographic information, resulting in enhanced
      diagnostic accuracy.

PMID- 9525563
TI  - Catheter closure of moderate- to large-sized patent ductus arteriosus using the
      new Amplatzer duct occluder: immediate and short-term results.
AB  - OBJECTIVES: The aim of this study was to assess the immediate and short-term
      results of anterograde catheter closure of a moderate- to large-sized patent
      ductus arteriosus (PDA) using the new self-expandable, respositionable Amplatzer
      duct occluder (ADO) device. BACKGROUND: Transcatheter closure of a PDA using
      devices or coils is technically challenging and may be accompanied by a 38%
      incidence of residual shunts. METHODS: Twenty-four patients (6 male, 18 female)
      underwent attempted transcatheter closure of a PDA using the ADO at a median age
      of 3.8 years (range 0.4 to 48) and a median weight of 15.5 kg (range 6 to 70).
      The mean PDA diameter at its narrowest segment was 3.7+/-1.5 mm. A 6F long sheath
      was used for delivery of the ADO. Follow-up evaluation was performed with color
      flow mapping of the main pulmonary artery within 24 h and at 1 and 3 months after
      closure. RESULTS: Twenty three of the 24 patients had successful device
      placement. Angiography showed that 7 patients had complete immediate closure, 14
      had a trace shunt (foaming through the device with no jet), and 2 had a small
      residual shunt (with a jet). Within 24 h, color Doppler revealed complete closure
      in all patients. The unsuccessful attempt was during an initial trial with a
      prototype that has been modified. The median fluoroscopy time was 13.5 min (range
      6.3 to 47). All patients were discharged home the next day. There were no
      complications. Of the 23 patients, 21 completed the 1-month follow-up, all (95%
      confidence interval [CI] 86% to 100%) with complete closure, and 18 of 23
      patients completed the 3-month follow-up, also all (95% CI 83% to 100%) with
      complete closure. CONCLUSIONS: Anterograde transcatheter closure using the new
      ADO is an effective therapy for patients with a PDA diameter up to 6 mm. Further
      clinical trials are underway.

PMID- 9525564
TI  - Primary arterial switch operation for transposition of the great arteries with
      intact ventricular septum in infants older than 21 days.
AB  - OBJECTIVES: The aim of this study was to assess the surgical outcome of the
      primary arterial switch operation (ASO) in infants 3 weeks to 2 months old.
      BACKGROUND: The surgical management of transposition of the great arteries and
      intact ventricular septum (TGA/IVS) beyond 2 to 3 weeks of age is controversial.
      Concern that regression of the left ventricular (LV) myocardial mass will render
      the left ventricle incapable of coping with the acutely increased work of
      systemic perfusion has been considered a contraindication to a primary ASO.
      METHODS: We used retrospective analysis of 37 patients 3 weeks to 2 months old
      and 156 patients <3 weeks old who underwent primary ASO with TGA/IVS to determine
      the surgical outcomes. RESULTS: Between January 1990 and December 1996, primary
      ASO was performed in 37 patients 21 to 61 days old (late ASO group) and 156
      patients <21 days old (early ASO group) with TGA/IVS. One (2.7%, 95% confidence
      interval [CI] 0.07% to 14.2%) of 37 patients and 13 (8.3%, 95% CI 4.5% to 13.8%)
      of 156 patients died. One late death occurred in each group. Mechanical LV
      support was required in 1 (2.7%, 95% CI 0.07% to 14.2%) of 37 late ASO and 6
      (3.8%, 95% CI 1.4% to 8.2%) of 156 early ASO group patients postoperatively.
      Neither death nor the need for mechanical LV support in the late ASO group
      patients could be attributed to LV failure. In the late ASO group, age, LV
      geometry, LV mass index, LV posterior wall thickness index, LV volume index, LV
      mass/volume ratio, patent arterial duct or pattern of coronary anatomy did not
      predict death, duration of postoperative ventilation or inotropic support or time
      in intensive care. Moreover, there was no difference in duration of ventilation,
      duration of inotropic support or the time spent in intensive care in comparison
      to a random sample of 37 neonates from the early ASO group. CONCLUSIONS: Primary
      ASO may be appropriate treatment for infants with TGA/IVS < or = 2 months old,
      regardless of preoperative echocardiographic variables. The upper age limit for
      which primary ASO is indicated in TGA/IVS is not yet defined.

PMID- 9525566
TI  - A symposium: Treatment of atrial fibrillation in the era of managed care.
      Introduction.

PMID- 9525565
TI  - ACC expert consensus document. Radiation safety in the practice of cardiology.
      American College of Cardiology.

PMID- 9525567
TI  - Acute treatment of atrial fibrillation: why and when to maintain sinus rhythm.
AB  - Although not usually immediately life threatening, atrial fibrillation (AFib)
      poses a significant long-term risk to health. The best-documented and probably
      largest long-term risk in this condition is from thromboembolic complications,
      but this has been shown to be largely overcome by moderate intensity
      anticoagulation. In addition, however, AFib has significant detrimental effects
      on exercise capacity and overall quality of life, can cause or exacerbate heart
      failure, and imposes significant health-care burdens. Cardioversion, usually by
      transthoracic direct current shock, restores sinus rhythm in > 80% of patients,
      but recurrence of AFib over the weeks and months that follow decreases the value
      of this strategy. Antiarrhythmic drugs lessen the recurrence rate and add to the
      overall efficacy of achieving the treatment goal of restoring and maintaining
      sinus rhythm, rather than accepting permanent AFib with ventricular rate control
      and long-term thromboembolic prophylaxis. Whereas clear evidence exists that
      abolishing AFib makes patients feel better in the short-to-medium term, data on
      the economic viability or long-term efficacy of such a strategy are sparse.
      Management trials in AFib currently ongoing will provide some answers, but the
      decision as to whether restoring sinus rhythm is feasible and realistic in
      individual patients will remain a decision to be made on a case-by-case basis.

PMID- 9525568
TI  - Acute treatment of atrial fibrillation.
AB  - Atrial fibrillation (AFib) is a common clinical entity, responsible for
      significant morbidity and mortality, but it also accounts for a large percentage
      of healthcare dollar expenditures. Efforts to treat this arrhythmia in the past
      have focused on subacute antithrombotic therapy and eventually use of
      antiarrhythmic drugs for maintenance of sinus rhythm. However, there has been a
      growing interest in the concept of acute electrical and pharmacologic conversion.
      This treatment strategy has a number of benefits, including immediate alleviation
      of patient symptoms, avoidance of antithrombotic therapy, and prevention of
      electrophysiologic remodeling, which is thought to contribute to the perpetuation
      of the arrhythmia. There is also increasing evidence that this is a cost
      effective strategy in that it may obviate admission to the hospital and the cost
      of long-term therapy. This article represents a summary of the treatments that
      may be used acutely to control the ventricular response to AFib, prevent
      thromboembolic events, and provide for acute conversion either pharmacologically
      or electrically. It includes information on modalities that are currently
      available and those that are under active development. We anticipate that an
      active, acute treatment approach to AFib and atrial flutter will become the
      therapeutic norm in the next few years, especially as the benefits of these
      interventions are demonstrated in clinical trials.

PMID- 9525569
TI  - Drug treatment of atrial fibrillation in the managed care era.
AB  - There are many reasons why one might wish to suppress atrial fibrillation (AFib)
      and attempt to maintain sinus rhythm. This article assumes that the clinical
      decision to maintain sinus rhythm has been made. That being the case,
      antiarrhythmic drug therapy is generally the first line of treatment of AFib.
      Currently in the United States, there are 8 available antiarrhythmic drugs that
      have demonstrated efficacy for preventing AFib. The drugs are quinidine,
      procainamide, disopyramide, flecainide, propafenone, moricizine, sotalol, and
      amiodarone. Because AFib tends to recur regardless of the drug selected,
      recurring in at least one-half of the patients being treated, no drug is clearly
      better than any other for suppression of AFib. Furthermore, because AFib is
      rarely life-threatening, occasional recurrence should be anticipated and should
      not be considered failure per se. The measure of drug efficacy is the frequency
      of recurrence. Before initiating drug therapy, the presence or absence of
      structural heart disease must be determined, because in the absence of structural
      heart disease, antiarrhythmic drugs generally can be given rather safely, but in
      the presence of structural heart disease, especially when associated with
      ventricular dysfunction, there is an important risk of developing ventricular
      proarrhythmia. Considerations for specific drug selection are discussed and an
      algorithm for therapy is suggested.

PMID- 9525570
TI  - Impact of managed care on the treatment of atrial fibrillation.
AB  - In the era of managed care, it has been necessary to develop new and innovative
      treatment strategies for the treatment of cardiovascular disease. This article
      examines our experience providing cardiovascular services to a large health
      maintenance organization (HMO). The focus of this article is on our development
      and implementation of a systematic approach to the management of atrial
      fibrillation (AFib), encouraging the active participation of the family practice
      and internal medicine physicians. With > 22 geographically diverse satellite
      clinics, the standardization of treatment of a common disease such as AFib is
      both challenging and difficult. The first objective for Baylor Cardiology was to
      adapt to such a system and provide an efficient and flexible schedule encouraging
      communication with the primary care doctor. A telephone consultation service was
      instituted to provide instant cardiology consultation. The HMO organizational
      structure allowed us to implement standardized procedures and clinical
      approaches. Guidelines were implemented to address all practical clinical issues
      in AFib such as: (1) the necessity for hospitalization; (2) baseline noninvasive
      studies; and (3) standardization of protime and international normalized ratio
      (INR) measurements between all the satellite clinics. Also, algorithms for the
      selection of antiarrhythmic drugs for maintenance of sinus rhythm and rate
      control are presented.

PMID- 9525571
TI  - Anticoagulation to prevent stroke in atrial fibrillation and its implications for
      managed care.
AB  - Nonrheumatic atrial fibrillation (AFib) is the most potent common risk factor for
      stroke, raising the risk of stroke 5-fold. Six randomized trials of
      anticoagulation in AFib consistently demonstrated a reduction in the risk of
      stroke by about two-thirds. In these trials, anticoagulation in AFib was quite
      safe. In contrast, randomized trials indicate that aspirin confers only a small
      reduction in risk of stroke, at best. Pooled data from the first set of
      randomized trials indicate that prior stroke, hypertension, diabetes, and
      increasing age are independent risk factors for future stroke with AFib.
      Individuals < 65 years old with none of the other risk factors might safely avoid
      anticoagulation; for all others, anticoagulation seems indicated. Studies of
      hemorrhagic risk highlight the importance of keeping the international normalized
      ratio (INR) < 4.0. Recent analyses also reveal that risk of ischemic stroke in
      AFib increases greatly at INR levels < 2.0. Efficacy and safety of
      anticoagulation in AFib depend on maintaining the INR between 2.0-3.0. Cost
      effectiveness studies indicate that anticoagulation for AFib is among the most
      efficient preventive interventions in adults. Importantly, the benefits of
      anticoagulation in AFib accrue immediately. The implications for managed care
      organizations are that anticoagulation for AFib should be encouraged in their
      covered populations, and that dedicated anticoagulation services should be
      developed to promote system-wide control of anticoagulation intensity. Quality
      measures would include the proportion of patients with AFib who are
      anticoagulated, and the percentage of time patients' INR levels are between 2.0
      3.0. Managed care organizations can benefit from recent research on
      anticoagulation for AFib; they have a responsibility to support future research
      and development efforts.

PMID- 9525572
TI  - Nonpharmacologic therapies for atrial fibrillation.
AB  - The limited efficacy and proarrhythmic risks of antiarrhythmic drug therapies for
      atrial fibrillation have led to the exploration of a wide spectrum of alternative
      therapeutic approaches. The diversity of the approaches is warranted by the
      current absence of a single procedure that can safely and effectively cure atrial
      fibrillation. The interventional therapies that are currently under most active
      development include implantable atrial defibrillator therapy, prophylactic atrial
      pacing in combination with drug therapy, multisite regional pace-entrainment of
      atrial fibrillation by rapid pacing, atrial surgery, and catheter ablation for
      atrial fibrillation. The current limitations of these procedures include: (1) for
      the implantable atrial defibrillator--patient tolerance of low energy shocks and
      early recurrence of atrial fibrillation; (2) for prophylactic pacing-limited
      efficacy in a small proportion of the total atrial fibrillation population; (3)
      for multisite regional pace-entrainment--lack of proved efficacy and difficulty
      in the expansion and merging of the entrained regions; (4) for atrial surgery-
      highly invasive as a stand-alone procedure; and (5) for catheter ablation-lack of
      proved long-term efficacy, shortcomings of currently available technology, and
      risk of thromboembolic stroke. It is evident that more basic and clinical
      research as well as technologic innovation are needed. However, it is likely that
      some of these new therapies, possibly in combination with antiarrhythmic drug
      therapy, will offer considerable clinical benefit to selected patients with
      symptomatic atrial fibrillation.

PMID- 9525573
TI  - Characterization of the DNA-binding domain of the bovine papillomavirus
      replication initiator E1.
AB  - The bovine papillomavirus replication initiator protein E1 is an origin of
      replication (ori)-binding protein absolutely required for viral DNA replication.
      In the presence of the viral transcription factor E2, E1 binds to the ori and
      initiates DNA replication. To understand how the E1 initiator recognizes the ori
      and how E2 assists in this process, we have expressed and purified a 166-amino
      acid fragment which corresponds to the minimal E1 DNA-binding domain (DBD). DNA
      binding studies using this protein demonstrate that the E1 DBD can bind to the
      palindromic E1 binding site in several forms but that binding of two monomers,
      each recognizing one half-site of the E1 palindrome, is the predominant form.
      This is reminiscent of the binding of the T-antigen DBD to the SV40 ori, and
      interestingly, the arrangement of E1 binding sites shows striking similarities to
      the arrangement of T-antigen binding sites in the SV40 ori even though the
      recognition sequences are unrelated. The E1 DBD is capable of interacting
      cooperatively with E2; however, the E2 DBD and not the E2 activation domain
      mediates this interaction. Furthermore, the E2 DBD stimulates binding of two
      monomers of the E1 DBD to the ori by binding cooperatively with one E1 monomer.
      Finally, we show that our results concerning the DNA-binding properties of the E1
      DBD can be extended to full-length E1.

PMID- 9525575
TI  - Analysis of hepatitis C virus-inoculated chimpanzees reveals unexpected clinical
      profiles.
AB  - The clinical course of hepatitis C virus (HCV) infections in a chimpanzee cohort
      was examined to better characterize the outcome of this valuable animal model.
      Results of a cross-sectional study revealed that a low percentage (39%) of HCV
      inoculated chimpanzees were viremic based on reverse transcription (RT-PCR)
      analysis. A correlation was observed between viremia and the presence of anti-HCV
      antibodies. The pattern of antibodies was dissimilar among viremic chimpanzees
      and chimpanzees that cleared the virus. Viremic chimpanzees had a higher
      prevalence of antibody reactivity to NS3, NS4, and NS5. Since an unexpectedly low
      percentage of chimpanzees were persistently infected with HCV, a longitudinal
      analysis of the virological profile of a small panel of HCV-infected chimpanzees
      was performed to determine the kinetics of viral clearance and loss of antibody.
      This study also revealed that a low percentage (33%) of HCV-inoculated
      chimpanzees were persistently viremic. Analysis of serial bleeds from six HCV
      infected animals revealed four different clinical profiles. Viral clearance with
      either gradual or rapid loss of anti-HCV antibody was observed in four animals
      within 5 months postinoculation. A chronic-carrier profile characterized by
      persistent HCV RNA and anti-HCV antibody was observed in two animals. One of
      these chimpanzees was RT-PCR positive, antibody negative for 5 years and thus
      represented a silent carrier. If extrapolated to the human population, these data
      would imply that a significant percentage of unrecognized HCV infections may
      occur and that silent carriers may represent potentially infectious blood donors.

PMID- 9525576
TI  - Glucagon treatment interferes with an early step of duck hepatitis B virus
      infection.
AB  - The effect of glucagon on the establishment of hepadnavirus infection was studied
      in vitro with the duck hepatitis B virus (DHBV) model. The presence of the
      peptide hormone throughout infection or starting up to 8 h after virus uptake
      resulted in a dose-dependent reduction in the levels of intra- and extracellular
      viral gene products and of secreted virions. Treatment with forskolin or
      dibutyryl-cyclic AMP, two drugs that also stimulate the cyclic AMP (cAMP) signal
      transduction pathway, resulted in comparable inhibition, suggesting that the
      inhibitor effect is related to changes in the activity of protein kinase A. In
      persistently infected hepatocytes, only a slight, but continuous, decrease in
      viral replication was observed upon prolonged drug treatment. Time course
      analysis, including detection of DHBV covalently closed circular (ccc) DNA
      templates, revealed that glucagon acts late during the establishment of
      infection, at a time when the virus is already internalized, but before
      detectable ccc DNA accumulation in the nucleus. These data suggest that nuclear
      import (and reimport) of DHBV DNA genomes from cytosolic capsids is subject to
      cAMP-mediated regulation by cellular factors responding to changes in the state
      of the host cell.

PMID- 9525574
TI  - Mtv-1 superantigen trafficks independently of major histocompatibility complex
      class II directly to the B-cell surface by the exocytic pathway.
AB  - Presentation of the Mtv-1 superantigen (vSag1) to specific Vbeta-bearing T cells
      requires association with major histocompatibility complex class II molecules.
      The intracellular route by which vSag1 trafficks to the cell surface and the site
      of vSag1-class II complex assembly in antigen-presenting B lymphocytes have not
      been determined. Here, we show that vSag1 trafficks independently of class II to
      the plasma membrane by the exocytic secretory pathway. At the surface of B cells,
      vSag1 associates primarily with mature peptide-bound class II alphabeta dimers,
      which are stable in sodium dodecyl sulfate. vSag1 is unstable on the cell surface
      in the absence of class II, and reagents that alter the surface expression of
      vSag1 and the conformation of class II molecules affect vSag1 stimulation of
      superantigen reactive T cells.

PMID- 9525577
TI  - Mutation of the Lck-binding motif of Tip enhances lymphoid cell activation by
      herpesvirus saimiri.
AB  - The proline-rich SH3-binding (SH3B) motif of the tyrosine kinase-interacting
      protein (Tip) of herpesvirus saimiri (HVS) is required for binding to the
      cellular Src family kinase Lck. We constructed a mutant form of HVS in which
      prolines in the SH3B motif of Tip were altered to alanines. This mutant form of
      Tip was incapable of binding to Lck. The mutant virus, HVS/Tip mSH3B, retained
      its ability to immortalize common marmoset lymphocytes in culture. In fact,
      common marmoset lymphocytes immortalized by the HVS/Tip mSH3B mutant displayed
      increased expression of HLA-DR lymphocyte activation marker, an altered pattern
      of tyrosine phosphorylation, increased expression of the tyrosine kinase Lyn, and
      a shift in electrophoretic mobility of Lck compared to cells immortalized by wild
      type HVS. Experimental infection of common marmosets resulted in fulminant
      lymphoma with both HVS/Tip mSH3B and wild-type HVS. However, HVS/Tip mSH3B
      produced greater infiltration of affected organs by proliferating lymphoid cells
      compared to wild-type HVS. These results demonstrate that Tip binding to Lck is
      not necessary for transformation and that abrogation of Tip binding to Lck alters
      the characteristics of transformed cells and the severity of the pathologic
      lesions.

PMID- 9525579
TI  - Inhibition of hepatitis B virus replication during adenovirus and cytomegalovirus
      infections in transgenic mice.
AB  - We have previously demonstrated that hepatitis B virus (HBV) replication and gene
      expression are abolished in the livers of HBV transgenic mice by cytotoxic T
      lymphocytes (CTLs) and during lymphocytic choriomeningitis virus (LCMV)
      infection, stimuli that trigger the production of alpha/beta interferon, gamma
      interferon, and tumor necrosis factor alpha in the liver. We now report that
      hepatic HBV replication and gene expression are inhibited by the local induction
      of these cytokines during adenovirus- and murine cytomegalovirus (MCMV)-induced
      hepatitis. Further, we show that MCMV also blocks HBV replication and gene
      expression in the proximal convoluted tubules of the kidney by causing
      interstitial nephritis and inducing the same cytokines in the renal parenchyma.
      These results suggest that inflammatory cytokines probably contribute to viral
      clearance during acute viral hepatitis in humans, and they imply that induction
      of these cytokines in the liver and other infected tissues of chronically
      infected patients might have therapeutic value.

PMID- 9525581
TI  - Generation of a mutant infectious bursal disease virus that does not cause bursal
      lesions.
AB  - A reverse genetics system for birnavirus, based on synthetic transcripts of the
      infectious bursal disease virus (IBDV) genome, was recently developed (E. Mundt
      and V. N. Vakharia, Proc. Natl. Acad. Sci. USA 93:11131-11136, 1996). To study
      the function of the 17-kDa nonstructural (NS) protein in viral growth and
      pathogenesis, we constructed a cDNA clone of IBDV segment A in which the first
      and only initiation codon (ATG) of NS protein was mutated to a stop codon (TAG).
      Transfection of Vero cells with combined transcripts of either modified or
      unmodified segment A, and with segment B, generated viable IBDV progeny. When
      chicken embryo fibroblast cells infected with transfectant viruses were analyzed
      by immunofluorescence assays using NS-specific antiserum, the mutant virus did
      not yield a fluorescence signal, indicating a lack of NS protein expression.
      Furthermore, replication kinetics and cytotoxic effects of the mutant virus were
      compared with those of the parental attenuated vaccine strain of IBDV (D78) in
      vitro. The mutant virus grew to slightly lower titers than D78 virus and
      exhibited decreased cytotoxic and apoptotic effects in cell culture. To evaluate
      the characteristics of the recovered viruses in vivo, we inoculated 3-week-old
      chickens with D78 or mutant virus and analyzed their bursa for histopathological
      lesions. The recovered D78 virus caused microscopic lesions and atrophy of the
      bursa, while the mutant virus failed to induce any pathological lesions or
      clinical signs of disease. In both instances, the virus was recovered from the
      bursa, and the presence or absence of mutation in these viruses was confirmed by
      nucleotide sequence analysis of NS gene. Although the mutant virus exhibited a
      delay in replication in vivo, it induced levels of IBDV neutralizing antibodies
      that were similar to those of D78 virus. In addition, no reversion of mutation
      was detected in the mutant virus recovered from inoculated chickens. These
      results demonstrate that NS protein is dispensable for viral replication in vitro
      and in vivo and that it plays an important role in viral pathogenesis. Thus,
      generation of such NS protein-deficient virus will facilitate the study of
      immunosuppression and aid in the development of live-attenuated vaccines for
      IBDV.

PMID- 9525578
TI  - Modulation of Sp1 phosphorylation by human immunodeficiency virus type 1 Tat.
AB  - We previously reported (K. T. Jeang, R. Chun, N. H. Lin, A. Gatignol, C. G.
      Glabe, and H. Fan, J. Virol. 67: 6224-6233, 1993) that human immunodeficiency
      virus type 1 (HIV-1) Tat and Sp1 form a protein-protein complex. Here, we have
      characterized the physical interaction and a functional consequence of Tat-Sp1
      contact. Using in vitro protein chromatography, we mapped the region in Tat that
      contacts Sp1 to amino acids 30 to 55. We found that in cell-free reactions, Tat
      augmented double-stranded DNA-dependent protein kinase (DNA-PK)-mediated Sp1
      phosphorylation in a contact-dependent manner. Tat mutants that do not bind Sp1
      failed to influence phosphorylation of the latter. In complementary experiments,
      we also found that Tat forms protein-protein contacts with DNA-PK. We confirmed
      that in HeLa and Jurkat cells, Tat expression indeed increased the intracellular
      amount of phosphorylated Sp1 in a manner consistent with the results of cell-free
      assays. Furthermore, using two phosphatase inhibitors and a kinase inhibitor, we
      demonstrated a modulation of reporter gene expression as a consequence of changes
      in Sp1 phosphorylation. Taken together, these findings suggest that activity at
      the HIV-1 promoter is influenced by phosphorylation of Sp1 which is affected by
      Tat and DNA-PK.

PMID- 9525580
TI  - Immune response to mouse mammary tumor virus in mice lacking the alpha/beta
      interferon or the gamma interferon receptor.
AB  - Mouse mammary tumor virus (MMTV) is a retrovirus which induces a strong immune
      response and a dramatic increase in the number of infected cells through the
      expression of a superantigen (SAg). Many cytokines are likely to be involved in
      the interaction between MMTV and the immune system. In particular, alpha/beta
      interferon (IFN-alpha/beta) and gamma interferon (IFN-gamma) exert many antiviral
      and immunomodulatory activities and play a critical role in other viral
      infections. In this study, we have investigated the importance of interferons
      during MMTV infection by using mice with a disrupted IFN-alpha/beta or IFN-gamma
      receptor gene. We found that the SAg response to MMTV was not modified in IFN
      alpha/betaR(0/0) and IFN-gammaR(0/0) mice. This was true both for the early
      expansion of B and T cells induced by the SAg and for the deletion of SAg
      reactive cells at later stages of the infection. In addition, no increase in the
      amount of proviral DNA was detected in tissues of IFN-alpha/betaR(0/0) and IFN
      gammaR(0/0) mice, suggesting that interferons are not essential antiviral defense
      mechanisms during MMTV infection. In contrast, IFN-gammaR(0/0) mice had increased
      amounts of IL-4 mRNA and an altered usage of immunoglobulin isotypes with a
      reduced frequency of IgG2a- and IgG3-producing cells. This was associated with
      lower titers of virus-specific antibodies in serum early after infection,
      although efficient titers were reached later.

PMID- 9525583
TI  - A replication-competent retrovirus arising from a split-function packaging cell
      line was generated by recombination events between the vector, one of the
      packaging constructs, and endogenous retroviral sequences.
AB  - Previously we reported the presence of a replication-competent retrovirus in
      supernatant from a vector-producing line derived from a widely used split
      function amphotropic packaging cell line. Rigorous routine screening of all
      retroviral stocks produced in our laboratory has not, previously or since,
      indicated the presence of such a virus. Replication-competent retroviruses have
      never previously been used in our laboratory, and stringent screening of all
      routinely used cell lines has not revealed the presence of any helper viruses.
      Therefore, it is highly unlikely that this virus represents an adventitious cross
      contaminant or had been imported unknowingly with our cell line stocks. PCR
      studies with DNA from infected cell lines and Northern blot analysis and reverse
      transcriptase PCR with RNA from infected cells suggest that the helper virus
      arose by recombination events, at sites of partial homology, between sequences in
      the vector, one of the packaging constructs, and endogenous retroviral elements.
      These recombinations were not present in stocks of the packaging cell line or in
      an initial stock of the vector-producing line, indicating that these events
      occurred while the vector-producing line was being passaged for harvest of
      supernatant stocks.

PMID- 9525582
TI  - Involvement of actin microfilaments in the replication of human parainfluenza
      virus type 3.
AB  - Several studies indicate that paramyxoviruses require a specific cellular
      factor(s) for transcription of their genomic RNAs. We previously reported that
      the cellular cytoskeletal protein actin, in its polymeric form, participates in
      the transcription of human parainfluenza virus type 3 (HPIV3) in vitro. In the
      present study, we investigated the role of the polymeric form of actin, i.e., the
      actin microfilaments of the cytoskeletal framework, in the reproduction of HPIV3
      in vivo. Pulse-chase labeling analyses indicate that the viral nucleocapsid
      associated proteins, NP and P, are present predominantly in the cytoskeletal
      framework during infection. By in situ hybridization, we found that viral mRNAs
      and genomic RNA were synthesized from the nucleocapsids that were bound to the
      cytoskeletal framework. Double immunofluorescent labeling and confocal microscopy
      of the cytoarchitecture revealed that the viral nucleocapsids are specifically
      localized on the actin microfilaments. Treatment of cells with the actin
      depolymerizing agent, cytochalasin D, resulted in the inhibition of viral RNA
      synthesis and ribonucleoprotein accumulation. These results strongly suggest that
      actin microfilaments play an important role in the replication of HPIV3.

PMID- 9525584
TI  - Packaging of endogenous retroviral sequences in retroviral vectors produced by
      murine and human packaging cells.
AB  - Interaction of retrovirus vectors and endogenous retroviruses present in
      packaging cell lines and target cells may result in unwanted events, such as the
      formation of recombinant viruses and the mobilization of therapeutic vectors.
      Using sensitive reverse transcriptase PCR assays, we investigated human and
      murine gene therapy packaging cell lines for incorporation of endogenous
      retrovirus transcripts into murine leukemia virus (MLV) vector particles and,
      conversely, whether vector genomes are incorporated into human endogenous
      retrovirus (HERV) particles. VL30 endogenous retrovirus sequences were
      efficiently packaged in particles produced by the murine AM12 packaging system.
      For every seven MLV-derived beta-galactosidase (beta-Gal) vector genomes present
      in the particles, one copy of VL30 was also packaged. Although human FLY
      packaging cells expressed several classes of HERV transcripts (HERV-K, HuRT, type
      C, and RTVL-H), none was detectable in the MLV vector particles released from the
      cells. Nonspecific packaging of the MLV Gag-Pol expression vector transcripts was
      detected in the FLY virions at a low level (1 in 17,000 sequences). These
      findings indicate that human packaging cells produce retrovirus particles far
      less contaminated by endogenous viral sequences than murine packaging cells.
      Human teratocarcinoma cells (GH cells), which produce HERV-K particles, were
      transduced with an MLV-derived beta-Gal vector. Although both HERV-K and RTVL-H
      sequences were found in association with the particles, beta-Gal transcripts were
      not detected, indicating that HERV Gag proteins do not efficiently package MLV
      based vectors.

PMID- 9525585
TI  - Mucosal immunity to herpes simplex virus type 2 infection in the mouse vagina is
      impaired by in vivo depletion of T lymphocytes.
AB  - Intravaginal (IVAG) inoculation of wild-type herpes simplex virus type 2 (HSV-2)
      in mice causes epithelial infection followed by lethal neurological illness,
      while IVAG inoculation of attenuated HSV-2 causes epithelial infection followed
      by development of protective immunity against subsequent IVAG challenge with wild
      type virus. The role of T cells in this immunity was studied by in vivo depletion
      of these cells with monoclonal antibodies. Three groups of mice were used for
      each experiment: nonimmune/challenged mice, immune/challenged mice, and immune
      depleted mice [immune mice depleted of a T-cell subset(s) shortly before
      challenge with HSV-2]. Mice were assessed for epithelial infection 24 h after
      challenge, virus protein in the vaginal lumen 3 days after challenge, and
      neurological illness 8 to 14 days after challenge. Monoclonal antibodies to CD4,
      CD8, or Thy-1 markedly reduced T cells in blood, spleen, and vagina, but major
      histocompatibility complex class II antigens were still partially upregulated in
      the vaginal epithelium after virus challenge, indicating that virus-specific
      memory T-cell function was not entirely eliminated from the vagina. Nevertheless,
      immune mice depleted of CD4+ and CD8+ T cells, Thy-1+ T cells, or CD8+ T cells
      alone had greater viral infection in the vaginal epithelium than nondepleted
      immune mice, indicating that T cells contribute to immunity against vaginal HSV-2
      infection. All immune depleted mice retained substantial immunity to epithelial
      infection and were immune to neurological illness, suggesting that other immune
      mechanisms such as virus-specific antibody may also contribute to immunity.

PMID- 9525586
TI  - In vivo evolution of a novel, syncytium-inducing and cytopathic feline leukemia
      virus variant.
AB  - Studies of feline leukemia virus (FeLV) have illustrated the importance of the
      genotype of the infecting virus in determining disease outcome. In FeLV
      infections, as in other retroviral infections, it is less clear how virus
      variants that evolve from the transmitted virus affect pathogenesis. We
      previously reported an analysis of the genotypic changes that occur in the viral
      envelope gene (env) in cats infected with a prototype transmissible FeLV clone,
      61E (J. Rohn, M. Linenberger, E. Hoover, and J. Overbaugh, J. Virol. 68:2458
      2467, 1994). In one cat, each variant (81T) had evolved, in addition to scattered
      amino acid changes, a four-amino-acid insertion with respect to 61E. This
      insertion was located at the same site in the extracellular envelope glycoprotein
      where the immunodeficiency-inducing molecular clone 61C possesses a six-amino
      acid insertion critical for its pathogenic phenotype, although the sequences of
      the insertions were distinct. To determine whether acquisition of the four-amino
      acid insertion was associated with a change in the replication or cytopathic
      properties of the virus, we constructed chimeras encoding 81T env genes in a 61E
      background. One representative chimeric virus, EET(TE)-109, was highly cytopathic
      despite the fact that it replicated with delayed kinetics in the feline T-cell
      line 3201 compared to the parental 61E virus. The phenotype of this virus was
      also novel compared to other FeLVs, including both the parental virus 61E and the
      immunodeficiency-inducing variant 61C, because infection of T cells was
      associated with syncytium formation. Moreover, in single-cycle infection assays,
      the 81T-109 envelope demonstrated receptor usage properties distinct from those
      of both 61E and 61C envelope. Thus, these studies demonstrate the evolution of a
      novel T-cell cytopathic and syncytium-inducing FeLV in the host. The 81T virus
      will be valuable for dissecting the mechanism of T-cell killing by cytopathic
      variants in the FeLV model.

PMID- 9525587
TI  - Separate DNA elements containing ATF/CREB and IE86 binding sites differentially
      regulate the human cytomegalovirus UL112-113 promoter at early and late times in
      the infection.
AB  - The human cytomegalovirus (HCMV) UL112-113 promoter represents a useful model for
      studying temporal regulation of viral gene expression. Stimulation of this
      promoter by the 86-kDa immediate-early protein (IE86) is controlled by sequences
      between nucleotides -113 and -59, which include both an ATF/CREB and an IE86
      binding site. In transient assays, the ATF/CREB site is essential, and the IE86
      site, although nonessential, can enhance transcription. With recombinant viruses,
      we have assessed the function of these promoter elements in the context of the
      viral genome. Transcription from the inserted UL112-113 promoter shows the same
      temporal pattern as the endogenous promoter, including the switch to an upstream
      RNA start site late in infection. Deletion of sequences containing the IE86 site
      results in a decrease in the level of early transcription and elimination of late
      transcription. In contrast, when the ATF/CREB site is deleted, early RNA
      synthesis is almost completely abolished, but late transcription is comparable to
      that of the wild type, with repositioning of the RNA start site downstream by the
      number of nucleotides deleted. Replacement of sequences between -108 and -95 with
      the HCMV cis-repression signal from the major immediate-early promoter had no
      effect on the level of late RNAs but resulted in the repositioning of the RNA
      start site 39 nucleotides upstream. These results suggest that the ATF/CREB site
      is functional only at early times, while sequences containing the IE86 site
      modulate the level of early RNAs and may be required for activating late
      transcription in a distance-dependent manner.

PMID- 9525588
TI  - Antirotavirus immunoglobulin A neutralizes virus in vitro after transcytosis
      through epithelial cells and protects infant mice from diarrhea.
AB  - Rotaviruses are the major cause of severe diarrhea in infants and young children
      worldwide. Due to their restricted site of replication, i.e., mature enterocytes,
      local intestinal antibodies have been proposed to play a major role in protective
      immunity. Whether secretory immunoglobulin A (IgA) antibodies alone can provide
      protection against rotavirus diarrhea has not been fully established. To address
      this question, a library of IgA monoclonal antibodies (MAbs) previously developed
      against different proteins of rhesus rotavirus was used. A murine hybridoma
      "backpack tumor" model was established to examine if a single MAb secreted onto
      mucosal surfaces via the normal epithelial transport pathway was capable of
      protecting mice against diarrhea upon oral challenge with rotavirus. Of several
      IgA and IgG MAbs directed against VP8 and VP6 of rotavirus, only IgA VP8 MAbs
      (four of four) were found to protect newborn mice from diarrhea. An IgG MAb
      recognizing the same epitope as one of the IgA MAbs tested failed to protect mice
      from diarrhea. We also investigated if antibodies could be transcytosed in a
      biologically active form from the basolateral domain to the apical domain through
      filter-grown Madin-Darby canine kidney (MDCK) cells expressing the polymeric
      immunoglobulin receptor. Only IgA antibodies with VP8 specificity (four of four)
      neutralized apically administered virus. The results support the hypothesis that
      secretory IgA antibodies play a major role in preventing rotavirus diarrhea.
      Furthermore, the results show that the in vivo and in vitro methods described are
      useful tools for exploring the mechanisms of viral mucosal immunity.

PMID- 9525589
TI  - Temporal usage of multiple promoters during the life cycle of human
      papillomavirus type 31b.
AB  - The life cycles of human papillomaviruses (HPVs) are dependent upon the
      differentiation of the epithelial cells they infect. HPV type 31b (HPV31b)
      virions can be purified following the growth of a latently HPV-infected cell line
      (CIN-612 9E) in the organotypic or raft system. Treatment of the CIN-612 9E raft
      tissues with protein kinase C (PKC) activators is required for upregulation of
      late gene expression and efficient production of virions. We employed the raft
      culture system to study the temporal usage of HPV31b promoters during the viral
      life cycle. We compared monolayer cultures of CIN-612 9E cells, untreated CIN-612
      9E raft tissues, and PKC-induced CIN-612 9E raft tissues harvested at various
      time points during epithelial differentiation. We found that the HPV31b major
      early promoter precisely maps to nucleotide (nt) 99 (P99). A transcriptional
      start site for both early and late gene transcripts mapped upstream of P99 at nt
      77 (P77). The P77 and P99 promoters were used constitutively throughout the
      HPV31b life cycle; however, initiation from P99 was much stronger than from P77.
      Mapping of the differentiation-induced P742 promoter revealed multiple start
      sites. These start sites were difficult to detect in monolayer cultures, were
      induced in untreated rafts, and were greatest in PKC-induced raft tissues at 8 to
      12 days. A constitutively active promoter, P3320, was also defined and is
      responsible for the transcription of unspliced and spliced RNAs containing E5a,
      E5b, L2, and L1 open reading frames.

PMID- 9525591
TI  - Immature dendritic cells selectively replicate macrophagetropic (M-tropic) human
      immunodeficiency virus type 1, while mature cells efficiently transmit both M-
      and T-tropic virus to T cells.
AB  - Dendritic cells (DCs) can develop from CD14+ peripheral blood monocytes cultured
      in granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin 4
      (IL-4). By 6 days in culture, the cells have the characteristics of immature DCs
      and can be further induced to mature by inflammatory stimuli or by monocyte
      conditioned medium. After infection with macrophagetropic (M-tropic) human
      immunodeficiency virus type 1 (HIV-1), monocytes and mature DCs show a block in
      reverse transcription and only form early transcripts that can be amplified with
      primers for the R/U5 region. In contrast, immature DCs cultured for 6 or 11 days
      in GM-CSF and IL-4 complete reverse transcription and show a strong signal when
      LTR/gag primers are used. Blood monocytes and mature DCs do not replicate HIV-1,
      whereas immature DCs can be productively infected, but only with M-tropic HIV-1.
      The virus produced by immature DCs readily infects activated T cells. Although
      mature DCs do not produce virus, these cells transmit both M- and T-tropic virus
      to T cells. In the cocultures, both DCs and T cells must express functional
      chemokine coreceptors for viral replication to occur. Therefore, the
      developmental stage of DCs can influence the interaction of these cells with HIV
      1 and influence the extent to which M-tropic and T-tropic virus can replicate.

PMID- 9525590
TI  - The I domain is required for efficient plasma membrane binding of human
      immunodeficiency virus type 1 Pr55Gag.
AB  - The interaction of the human immunodeficiency virus type 1 (HIV-1) Pr55Gag
      molecule with the plasma membrane of an infected cell is an essential step of the
      viral life cycle. Myristic acid and positively charged residues within the N
      terminal portion of MA constitute the membrane-binding domain of Pr55Gag. A
      separate assembly domain, termed the interaction (I) domain, is located nearer
      the C-terminal end of the molecule. The I domain is required for production of
      dense retroviral particles, but has not previously been described to influence
      the efficiency of membrane binding or the subcellular distribution of Gag. This
      study used a series of Gag-green fluorescent protein fusion constructs to define
      a region outside of MA which determines efficient plasma membrane interaction.
      This function was mapped to the nucleocapsid (NC) region of Gag. The minimal
      region in a series of C-terminally truncated Gag proteins conferring plasma
      membrane fluorescence was identified as the N-terminal 14 amino acids of NC. This
      same region was sufficient to create a density shift in released retrovirus-like
      particles from 1.13 to 1.17 g/ml. The functional assembly domain previously
      termed the I domain is thus required for the efficient plasma membrane binding of
      Gag, in addition to its role in determining the density of released particles. We
      propose a model in which the I domain facilitates the interaction of the N
      terminal membrane-binding domain of Pr55Gag with the plasma membrane.

PMID- 9525592
TI  - Characterization of hepatitis G virus (GB-C virus) particles: evidence for a
      nucleocapsid and expression of sequences upstream of the E1 protein.
AB  - Hepatitis G virus (HGV or GB-C virus) is a newly described virus that is closely
      related to hepatitis C virus (HCV). Based on sequence analysis and by evaluation
      of translational initiation codon preferences utilized during in vitro
      translation, HGV appears to have a truncated or absent core protein at the amino
      terminus of the HGV polyprotein. Consequently, the biophysical properties of HGV
      may be very different from those of HCV. To characterize HGV particle types, we
      evaluated plasma from chronically infected individuals with and without
      concomitant HCV infection by using sucrose gradient centrifugation, isopycnic
      banding in cesium chloride, and saline density flotation centrifugation. Similar
      to HCV, HGV particles included an extremely-low-density virion particle (1.07 to
      1.09 g/ml) and a nucleocapsid of approximately 1.18 g/ml. One major difference
      between the particle types was that HGV was consistently more stable in cesium
      chloride than HCV. Plasma samples from chronically HGV-infected individuals and
      controls were assessed by a synthetic peptide-based immunoassay to determine if
      they contained HGV antibody specific for a conserved region in the coding region
      upstream of the E1 protein. Chronically HGV-infected individuals contained
      antibody to the HGV core protein peptide, whereas no binding to a hepatitis A
      virus peptide control was observed. Competitive inhibition of binding to the HGV
      peptide confirmed the specificity of the assay. These data indicate that HGV has
      a nucleocapsid and that at least part of the putative core region of HGV is
      expressed in vivo.

PMID- 9525593
TI  - Herpes simplex virus DNA packaging without measurable DNA synthesis.
AB  - Herpes simplex virus (HSV) type 1 DNA synthesis and packaging occur within the
      nuclei of infected cells; however, the extent to which the two processes are
      coupled remains unclear. Correct packaging is thought to be dependent upon DNA
      debranching or other repair processes, and such events commonly involve new DNA
      synthesis. Furthermore, the HSV UL15 gene product, essential for packaging,
      nevertheless localizes to sites of active DNA replication and may link the two
      events. It has previously been difficult to determine whether packaging requires
      concomitant DNA synthesis due to the complexity of these processes and of the
      viral life cycle; however, we have recently described a model system which
      simplifies the study of HSV assembly. Cells infected with HSV strain tsProt.A
      accumulate unpackaged capsids at the nonpermissive temperature of 39 degrees C.
      Following release of the temperature block, these capsids proceed to package
      viral DNA in a single, synchronous wave. Here we report that, when DNA
      replication was inhibited prior to release of the temperature block, DNA
      packaging and later events in viral assembly nevertheless occurred at near-normal
      levels. We conclude that, under our conditions, HSV DNA packaging does not
      require detectable levels of DNA synthesis.

PMID- 9525595
TI  - The quantity of latent viral DNA correlates with the relative rates at which
      herpes simplex virus types 1 and 2 cause recurrent genital herpes outbreaks.
AB  - Herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) have evolved specific
      anatomic tropisms and site-dependent rates of reactivation. To determine whether
      reactivation rates depend on distinct abilities of HSV-1 and -2 to establish
      latency and to express latency-associated transcripts (LATs), virulent strains of
      each virus were studied in the guinea pig genital model. Following infection with
      equivalent titers of virus, the quantities of latent HSV-2 genomes and LATs were
      higher in lumbosacral ganglia, and HSV-2 infections recurred more frequently and
      lasted longer than HSV-1 infections. In contrast, if the inoculum of HSV-1 was 10
      times that of HSV-2, the quantity of HSV-1 DNA and LATs increased correspondingly
      and HSV-1 infections were as likely to recur as those with HSV-2. The quantity of
      latent virus DNA correlates with and may be a major determinant of the site
      specific patterns and rates of reactivation of HSV-1 and -2.

PMID- 9525594
TI  - RNase L mediates the antiviral effect of interferon through a selective reduction
      in viral RNA during encephalomyocarditis virus infection.
AB  - The 2',5'-oligoadenylate (2-5A) system is an RNA degradation pathway which plays
      an important role in the antipicornavirus effects of interferon (IFN). RNase L,
      the terminal component of the 2-5A system, is thought to mediate this antiviral
      activity through the degradation of viral RNA; however, the capacity of RNase L
      to selectively target viral RNA has not been carefully examined in intact cells.
      Therefore, the mechanism of RNase L-mediated antiviral activity was investigated
      following encephalomyocarditis virus (EMCV) infection of cell lines in which
      expression of transfected RNase L was induced or endogenous RNase L activity was
      inhibited. RNase L induction markedly enhanced the anti-EMCV activity of IFN via
      a reduction in EMCV RNA. Inhibition of endogenous RNase L activity inhibited this
      reduction in viral RNA. RNase L had no effect on IFN-mediated protection from
      vesicular stomatitis virus. RNase L induction reduced the rate of EMCV RNA
      synthesis, suggesting that RNase L may target viral RNAs involved in replication
      early in the virus life cycle. The RNase L-mediated reduction in viral RNA
      occurred in the absence of detectable effects on specific cellular mRNAs and
      without any global alteration in the cellular RNA profile. Extensive rRNA
      cleavage, indicative of high levels of 2-5A, was not observed in RNase L-induced,
      EMCV-infected cells; however, transfection of 2-5A into cells resulted in
      widespread degradation of cellular RNAs. These findings provide the first
      demonstration of the selective capacity of RNase L in intact cells and link this
      selective activity to cellular levels of 2-5A.

PMID- 9525596
TI  - Generation of replication-competent hepatitis B virus nucleocapsids in insect
      cells.
AB  - The double-stranded DNA genome of human hepatitis B virus (HBV) and related
      hepadnaviruses is reverse transcribed from a pregenomic RNA by a viral polymerase
      (Pol) harboring both priming and RNA- and DNA-dependent elongation activities.
      Although hepadnavirus replication occurs inside viral nucleocapsids, or cores,
      biochemical systems for analyzing this reaction are currently limited to
      unencapsidated Pols expressed in heterologous systems. Here, we describe cis and
      trans classes of replicative HBV cores, produced in the recombinant baculovirus
      system via coexpression of HBV core and Pol proteins from either a single RNA
      (i.e., in cis) or two distinct RNAs (in trans). Upon isolation from insect cells,
      cis and trans cores contained Pol-linked HBV minus-strand DNA with 5' ends
      mapping to the authentic elongation origin DR1 and also plus-strand DNA species.
      Only trans cores, however, were highly active for the de novo priming and reverse
      transcription of authentic HBV minus strands in in vitro endogenous polymerase
      assays. This reaction strictly required HBV Pol but not the epsilon stem-loop
      element, although the presence of one epsilon, or better, two epsilons, enhanced
      minus-strand synthesis up to 10-fold. Compared to unencapsidated Pol enzymes,
      encapsidated Pol appeared to be (i) highly processive, able to extend minus
      strand DNAs of 400 nucleotides from DR1 in vitro, and (ii) more active for HBV
      plus-strand synthesis. These observations suggest possible contributions to the
      replication process from the HBV core protein. These novel core reagents should
      facilitate the analysis of HBV replication in its natural environment, the
      interior of the capsid, and also fuel the development of new anti-HBV drug
      screens.

PMID- 9525598
TI  - Plasma membrane-targeted Raf kinase activates NF-kappaB and human
      immunodeficiency virus type 1 replication in T lymphocytes.
AB  - Increasing evidence points to a role of the mitogenic Ras/Raf/MEK/ERK signaling
      cascade in regulation of human immunodeficiency virus type 1 (HIV-1) gene
      expression. Stimulation of elements of this pathway leads to transactivation of
      the HIV-1 promoter. In particular, the NF-kappaB motif in the HIV long terminal
      repeat (LTR) represents a Raf-responsive element in fibroblasts. Regulation of
      the Raf kinase in T cells differs from findings with a variety of cell lines that
      the catalytic domain of Raf (Raf(delta26-303)) shows no activity. In this study,
      we restored the activity of the kinase in T cells by fusing its catalytic domain
      to the CAAX motif (-Cx) of Ras, thus targeting the enzyme to the plasma membrane.
      Constitutive activity of Raf was demonstrated by phosphorylation of mitogen
      activated protein kinase kinase (MEK) and endogenous mitogen-activated protein
      kinase 1/2 (ERK1/2) in A3.01 T cells transfected with Raf(delta26-303)-Cx.
      Membrane-targeted Raf also stimulates NF-kappaB, as judged by kappaB-dependent
      reporter assays and enhanced NF-kappaB p65 binding on band shift analysis.
      Moreover, we found that active Raf transactivates the HIV(NL4-3) LTR in A3.01 T
      lymphocytes and that dominant negative Raf (C4) blocked 12-O-tetradecanoylphorbol
      13-acetate induced transactivation. When cotransfected with infectious HIV(NL4-3)
      DNA, membrane-targeted Raf induces viral replication up to 10-fold over basal
      levels, as determined by the release of newly synthesized p24gag protein. Our
      study clearly demonstrates that the activity of the catalytic domain of Raf in
      A3.01 T cells is dependent on its cellular localization. The functional
      consequences of active Raf in T lymphocytes include not only NF-kappaB activation
      and transactivation of the HIV(NL4-3) LTR but also synthesis and release of HIV
      particles.

PMID- 9525597
TI  - Cellular proteins required for adeno-associated virus DNA replication in the
      absence of adenovirus coinfection.
AB  - We previously reported the development of an in vitro adeno-associated virus
      (AAV) DNA replication system. The system required one of the p5 Rep proteins
      encoded by AAV (either Rep78 or Rep68) and a crude adenovirus (Ad)-infected HeLa
      cell cytoplasmic extract to catalyze origin of replication-dependent AAV DNA
      replication. However, in addition to fully permissive DNA replication, which
      occurs in the presence of Ad, AAV is also capable of partially permissive DNA
      replication in the absence of the helper virus in cells that have been treated
      with genotoxic agents. Limited DNA replication also occurs in the absence of Ad
      during the process of establishing a latent infection. In an attempt to isolate
      uninfected extracts that would support AAV DNA replication, we discovered that
      HeLa cell extracts grown to high density can occasionally display as much in
      vitro replication activity as Ad-infected extracts. This finding confirmed
      previous genetic analyses which suggested that no Ad-encoded proteins were
      absolutely essential for AAV DNA replication and that the uninfected extracts
      should be useful for studying the differences between helper-dependent and helper
      independent AAV DNA replication. Using specific chemical inhibitors and
      monoclonal antibodies, as well as the fractionation of uninfected HeLa extracts,
      we identified several of the cellular enzymes involved in AAV DNA replication.
      They were the single-stranded DNA binding protein, replication protein A (RFA),
      the 3' primer binding complex, replication factor C (RFC), and proliferating cell
      nuclear antigen (PCNA). Consistent with the current model for AAV DNA
      replication, which requires only leading-strand DNA synthesis, we found no
      requirement for DNA polymerase alpha-primase. AAV DNA replication could be
      reconstituted with purified Rep78, RPA, RFC, and PCNA and a phosphocellulose
      chromatography fraction (IIA) that contained DNA polymerase activity. As both RFC
      and PCNA are known to be accessory proteins for polymerase delta and epsilon, we
      attempted to reconstitute AAV DNA replication by substituting either purified
      polymerase delta or polymerase epsilon for fraction IIA. These attempts were
      unsuccessful and suggested that some novel cellular protein or modification was
      required for AAV DNA replication that had not been previously identified.
      Finally, we also further characterized the in vitro DNA replication assay and
      demonstrated by two-dimensional (2D) gel electrophoresis that all of the
      intermediates commonly seen in vivo are generated in the in vitro system. The
      only difference was an accumulation of single-stranded DNA in vivo that was not
      seen in vitro. The 2D data also suggested that although both Rep78 and Rep68 can
      generate dimeric intermediates in vitro, Rep68 is more efficient in processing
      dimers to monomer duplex DNA. Regardless of the Rep that was used in vitro, we
      found evidence of an interaction between the elongation complex and the terminal
      repeats. Nicking at the terminal repeats of a replicating molecule appeared to be
      inhibited until after elongation was complete.

PMID- 9525600
TI  - Genotype-specific complementation of hepatitis delta virus RNA replication by
      hepatitis delta antigen.
AB  - Characterizations of genetic variations among hepatitis delta virus (HDV)
      isolates have focused principally on phylogenetic analysis of sequences, which
      vary by 30 to 40% among three genotypes and about 10 to 15% among isolates of the
      same genotype. The significance of the sequence differences has been unclear but
      could be responsible for pathogenic variations associated with the different
      genotypes. Studies of the mechanisms of HDV replication have been limited to cDNA
      clones from HDV genotype I, which is the most common. To perform a comparative
      analysis of HDV RNA replication in genotypes I and III, we have obtained a full
      length cDNA clone from an HDV genotype III isolate. In transfected Huh-7 cells,
      the functional roles of the two forms of the viral protein, hepatitis delta
      antigen (HDAg), in HDV RNA replication are similar for both genotypes I and III;
      the short form is required for RNA replication, while the long form inhibits
      replication. For both genotypes, HDAg was able to support replication of RNAs of
      the same genotype that were mutated so as to be defective for HDAg production.
      Surprisingly, however, neither genotype I nor genotype III HDAg was able to
      support replication of such mutated RNAs of the other genotype. The inability of
      genotype III HDAg to support replication of genotype I RNA could have been due to
      a weak interaction between the RNA and HDAg. The clear genotype-specific activity
      of HDAg in supporting HDV RNA replication confirms the original categorization of
      HDV sequences in three genotypes and further suggests that these should be
      referred to as types (i.e., HDV-I and HDV-III) rather than genotypes.

PMID- 9525599
TI  - Interferon resistance of hepatitis C virus genotype 1b: relationship to
      nonstructural 5A gene quasispecies mutations.
AB  - A 40-amino-acid sequence located in the nonstructural 5A (NS5A) protein of
      hepatitis C virus genotype 1b (HCV-1b) was recently suggested to be the
      interferon sensitivity-determining region (ISDR), because HCV-1b strains with an
      ISDR amino acid sequence identical to that of the prototype strain HCV-J were
      found to be resistant to alpha interferon (IFN-alpha) whereas strains with amino
      acid substitutions were found to be sensitive (N. Enomoto, I. Sakuma, Y. Asahina,
      M. Kurosaki, T. Murakami, C. Yamamoto, N. Izumi, F. Marumo, and C. Sato, J. Clin.
      Invest. 96:224-230, 1995; N. Enomoto, I. Sakuma, Y. Asahina, M. Kurosaki, T.
      Murakami, C. Yamamoto, Y. Ogura, N. Izumi, F. Marumo, and C. Sato, N. Engl. J.
      Med. 334:77-81, 1996). We used single-strand conformation polymorphism (SSCP)
      analysis, combined with cloning and sequencing strategies, to characterize NS5A
      quasispecies in HCV-1b-infected patients and determine the relationships between
      pre- and posttreatment NS5A quasispecies mutations and the IFN-alpha sensitivity
      of HCV-1b. The serine residues involved in phosphorylation of NS5A protein were
      highly conserved both in the various patients and in quasispecies in a given
      patient, suggesting that phosphorylation is important in NS5A protein function. A
      hot spot for amino acid substitutions was found at positions 2217 to 2218; it
      could be the result of either strong selection pressure or tolerance to these
      amino acid replacements. The proportion of synonymous mutations was significantly
      higher than the proportion of nonsynonymous mutations, suggesting that genetic
      variability in the region studied was the result of high mutation rates and viral
      replication kinetics rather than of positive selection. Sustained HCV RNA
      clearance was associated with low viral load and low nucleotide sequence entropy,
      suggesting (i) that the replication kinetics when treatment is started plays a
      critical role in HCV-1b sensitivity to IFN-alpha and (ii) that HCV-1b resistance
      to IFN-alpha could be conferred by numerous and/or related mutations that could
      be patient specific and located at different positions throughout the viral
      genome and could allow escape variants to be selected by IFN-alpha-stimulated
      immune responses. No NS5A sequence appeared to be intrinsically resistant or
      sensitive to IFN-alpha, but the HCV-J sequence was significantly more frequent in
      nonresponder quasispecies than in sustained virological responder quasispecies,
      suggesting that the balance between NS5A quasispecies sequences in infected
      patients could have a subtle regulatory influence on HCV replication.

PMID- 9525602
TI  - Suppressors of cleavage-site mutations in the p62 envelope protein of Semliki
      Forest virus reveal dynamics in spike structure and function.
AB  - The E2 spike glycoprotein of Semliki Forest virus is produced as a p62 precursor
      protein, which is cleaved by host proteases to its mature form, E2. Cleavage is
      not necessary for particle formation or release but is necessary for infectivity.
      Previous results had shown that phenotypic revertants of cleavage-deficient p62
      mutants are generated, and here we show that these may contain second-site
      suppressor mutations in the vicinity of the cleavage site. These hot-spot sites
      were mutated to abolish the generation of such suppressor mutations; however,
      secondary mutations in another distant domain of the E2 protein appeared instead,
      all of which still caused cleavage-deficient mutations. Such mutants grew very
      poorly and were inefficient in virus entry and release. The mutated sites define
      domains of the spike protein which probably interact to regulate its structure
      and function. Because of their highly attenuated phenotype and the lower
      probability of reversion, the new mutations close to the cleavage site were used
      to make new helper vectors for packaging of recombinant RNA into infectious
      particles, thus increasing further the biosafety of the vector system based on
      the Semliki Forest virus replicon.

PMID- 9525601
TI  - Expression of the pRb-binding regions of E1A enables efficient transformation of
      primary epithelial cells by v-src.
AB  - Primary cultures of rat embryo fibroblasts have been shown to be resistant to
      transformation by dominant oncogenes such as v-src. We sought to determine if
      similar resistance is displayed by primary epithelial cells, and, if so, whether
      an immortalizing oncogene such as E1A could enhance transformation of primary
      epithelial cells by v-src. Transformation of primary rat epithelial cells by v
      src was synergistically enhanced when E1A expression plasmids were cotransfected
      with a v-src expression plasmid. Foci were more numerous and observed earlier (9
      to 14 days) with E1A plus v-src than with v-src alone (18 to 28 days). This
      cotransformation ability was abrogated by deletions in CR1 or CR2 of E1A, which
      encode the binding regions for the pRb family and are responsible for E1A
      mediated cell cycle activation. Mutations in the p300 binding site or the second
      exon, which abolish immortalization, did not affect v-src cooperation, in
      contrast to ras and adenovirus E1B. While kinase activation was required for
      growth in soft agar, differential activation of Src kinase did not correlate with
      transformation efficiency. Cell morphology and actin structures were not
      dramatically impacted by E1A expression; thus, hypertransformation, as previously
      described for ras cotransformation, was not observed with v-src and second-exon
      mutants of E1A. However, growth rates for cells expressing both E1A and v-Src
      were higher than those for cells expressing only v-Src. These results suggest
      that functions involved in cell cycle activation encoded by E1A first exon can
      enhance v-src transformation of primary epithelial cells.

PMID- 9525603
TI  - Specific interactions between retrovirus Env and Gag proteins in rat neurons.
AB  - In this work we have studied the intracellular localization properties of the Gag
      and Env proteins of Moloney murine leukemia virus (MLV) and human
      immunodeficiency virus (HIV) in dorsal root ganglion (DRG) neurons of rat. These
      neurons form thick bundles of axons, which facilitates protein localization
      studies by immunofluorescence analyses. When such neuron cultures were infected
      with recombinant Semliki Forest virus particles carrying the gag genes of either
      retrovirus, the expressed Gag proteins were localized to both the somatic and the
      axonal regions of the DRG neurons. In contrast, the Env proteins were confined
      only to the somatic region. When the Gag and Env proteins were coexpressed, the
      Gag proteins were also excluded from the axons. This effect of the Env proteins
      was shown to be dependent on the concentration of the Gag proteins in the neuron
      and also to be specific for homologous pairs of retrovirus proteins. Therefore,
      the results suggest that there are specific interactions between the Env and the
      Gag proteins of MLV and HIV in the DRG neurons.

PMID- 9525605
TI  - Effects of CCR5 and CD4 cell surface concentrations on infections by
      macrophagetropic isolates of human immunodeficiency virus type 1.
AB  - It has been proposed that changes in cell surface concentrations of coreceptors
      may control infections by human immunodeficiency virus type 1 (HIV-1), but the
      mechanisms of coreceptor function and the concentration dependencies of their
      activities are unknown. To study these issues and to generate stable clones of
      adherent cells able to efficiently titer diverse isolates of HIV-1, we generated
      two panels of HeLa-CD4/CCR5 cells in which individual clones express either large
      or small quantities of CD4 and distinct amounts of CCR5. The panels were made by
      transducing parental HeLa-CD4 cells with the retroviral vector SFF-CCR5.
      Derivative clones expressed a wide range of CCR5 quantities which were between
      7.0 x 10(2) and 1.3 x 10(5) molecules/cell as measured by binding antibodies
      specific for CCR5 and the chemokine [125I]MIP1beta. CCR5 was mobile in the
      membranes, as indicated by antibody-induced patching. In cells with a large
      amount of CD4, an unexpectedly low trace of CCR5 (between 7 x 10(2) and 2.0 x
      10(3) molecules/cell) was sufficient for maximal susceptibility to all tested HIV
      1, including primary patient macrophagetropic and T-cell-tropic isolates. Indeed,
      the titers as indicated by immunoperoxidase staining of infected foci were as
      high as the tissue culture infectious doses measured in human peripheral blood
      mononuclear cells. In contrast, cells with a small amount of CD4 required a much
      larger quantity of CCR5 for maximal infection by macrophagetropic HIV-1 (ca. 1.0
      x 10(4) to 2.0 x 10(4) molecules/cell). Cells that expressed low and high amounts
      of CD4 were infected with equal efficiencies when CCR5 concentrations were above
      threshold levels for maximal infection. Our results suggest that the
      concentrations of CD4 and CCR5 required for efficient infections by
      macrophagetropic HIV-1 are interdependent and that the requirements for each are
      increased when the other component is present in a limiting amount. We conclude
      that CD4 and CCR5 directly or indirectly interact in a concentration-dependent
      manner within a pathway that is essential for infection by macrophagetropic HIV
      1. In addition, our results suggest that multivalent virus-receptor bonds and
      diffusion in the membrane contribute to HIV-1 infections.

PMID- 9525606
TI  - Role of actin microfilaments in Black Creek Canal virus morphogenesis.
AB  - We have investigated the involvement of cytoskeletal proteins in the
      morphogenesis of Black Creek Canal virus (BCCV), a New World hantavirus.
      Immunofluorescent staining of BCCV-infected cells revealed a filamentous pattern
      of virus antigen, the appearance of which was sensitive to treatment with
      cytochalasin D, an actin microfilament-depolymerizing drug. Double
      immunofluorescence staining of BCCV-infected Vero cells with anti-BCCV
      nucleocapsid (N) monoclonal antibody and phalloidin revealed a colocalization of
      the BCCV N protein with actin microfilaments. A similar, though less prominent,
      filamentous pattern was observed in BHK21 cells transiently expressing the BCCV N
      protein alone but not in cells expressing the BCCV G1 and G2 glycoproteins.
      Moreover, the association of the N protein with actin microfilaments was
      confirmed by coimmunoprecipitation with beta-actin-specific antibody. Treatment
      of the BCCV-infected Vero cells at 3 days postinfection with cytochalasin D
      decreased the yield of released BCCV by 94% relative to the yield from untreated
      cells. Pretreatment of Vero cells with cytochalasin D prior to and during BCCV
      adsorption and entry had no effect on the outcome of virus production. These
      results indicate that actin filaments may play an important role in hantavirus
      assembly and/or release.

PMID- 9525604
TI  - Sequential steps in human immunodeficiency virus particle maturation revealed by
      alterations of individual Gag polyprotein cleavage sites.
AB  - Retroviruses are produced as immature particles containing structural
      polyproteins, which are subsequently cleaved by the viral proteinase (PR).
      Extracellular maturation leads to condensation of the spherical core to a capsid
      shell formed by the capsid (CA) protein, which encases the genomic RNA complexed
      with nucleocapsid (NC) proteins. CA and NC are separated by a short spacer
      peptide (spacer peptide 1 [SP1]) on the human immunodeficiency virus type 1 (HIV
      1) Gag polyprotein and released by sequential PR-mediated cleavages. To assess
      the role of individual cleavages in maturation, we constructed point mutations
      abolishing cleavage at these sites, either alone or in combination. When all
      three sites between CA and NC were mutated, immature particles containing stable
      CA-NC were observed, with no apparent effect on other cleavages. Delayed
      maturation with irregular morphology of the ribonucleoprotein core was observed
      when cleavage of SP1 from NC was prevented. Blocking the release of SP1 from CA,
      on the other hand, yielded normal condensation of the ribonucleoprotein core but
      prevented capsid condensation. A thin, electron-dense layer near the viral
      membrane was observed in this case, and mutant capsids were significantly less
      stable against detergent treatment than wild-type HIV-1. We suggest that HIV
      maturation is a sequential process controlled by the rate of cleavage at
      individual sites. Initial rapid cleavage at the C terminus of SP1 releases the
      RNA-binding NC protein and leads to condensation of the ribonucleoprotein core.
      Subsequently, CA is separated from the membrane by cleavage between the matrix
      protein and CA, and late release of SP1 from CA is required for capsid
      condensation.

PMID- 9525607
TI  - Priming with secreted glycoprotein G of respiratory syncytial virus (RSV)
      augments interleukin-5 production and tissue eosinophilia after RSV challenge.
AB  - The respiratory syncytial virus (RSV) G glycoprotein promotes differentiation of
      type 2 CD4+ T lymphocytes and induces an eosinophilic response in lungs of RSV
      infected mice. A unique feature of G is that a second initiation codon in the
      transmembrane region of the glycoprotein results in secretion of soluble protein
      from infected cells. Recombinant vaccinia viruses that express wild-type G (vvWT
      G), only secreted G (vvM48), or only membrane-anchored G (vvM48I) were used to
      define the influence of G priming on immunopathogenesis. Mice immunized with
      vvM48 had more severe illness following RSV challenge than did mice primed with
      vvWT G or vvM48I. Coadministration of purified G during priming with the
      construct expressing membrane-anchored G shifted immune responses following RSV
      challenge to a more Th2-like response. This was characterized by increased
      interleukin-5 in lung supernatants and an increase in G-specific immunoglobulin
      G1 antibodies. Eosinophils were present in the infiltrate of all mice primed with
      G-containing vectors but were greatest in mice primed with regimens including
      secreted G. These data suggest the form of G protein available for initial
      antigen processing and presentation is an important factor in promoting Th2-like
      immune responses, including the induction of lung eosinophilia. The ability of
      RSV to secrete G protein may therefore represent a viral strategy for
      immunomodulation and be a key determinant of disease pathogenesis.

PMID- 9525609
TI  - The impact of multidideoxynucleoside resistance-conferring mutations in human
      immunodeficiency virus type 1 reverse transcriptase on polymerase fidelity and
      error specificity.
AB  - Variants of human immunodeficiency virus type 1 (HIV-1) that are highly resistant
      to a number of nucleoside analog drugs have been shown to develop in some
      patients receiving 2',3'-dideoxy-3'-azidothymidine therapy in combination with
      2',3'-dideoxycytidine or 2',3'-dideoxyinosine. The appearance, in the reverse
      transcriptase (RT), of the Q151M mutation in such variants precedes the
      sequential appearance of three or four additional mutations, resulting in a
      highly resistant virus. Three of the affected residues are proposed to lie in the
      vicinity of the template-primer in the three-dimensional structure of the HIV-1
      RT-double-stranded DNA complex. The amino acid residue Q151 is thought to be very
      near the templating base. The nucleoside analog resistance mutations in the beta9
      beta10 (M184V) and the beta5a (E89G) strands of HIV-1 RT were previously shown to
      increase the fidelity of deoxynucleoside triphosphate insertion. Therefore, we
      have examined wild-type HIV-1BH10 RT and two nucleoside analog-resistant
      variants, the Q151M and A62V/V75I/F77L/F116Y/Q151M (VILYM) RTs, for their overall
      forward mutation rates in an M13 gapped-duplex assay that utilizes lacZ alpha as
      a reporter. The overall error rates for the wild-type, the Q151M, and the VILYM
      RTs were 4.5 x 10(-5), 4.0 x 10(-5), and 2.3 x 10(-5) per nucleotide,
      respectively. Although the mutant RTs displayed minimal decreases in the overall
      error rates compared to wild-type RT, the error specificities of both mutant RTs
      were altered. The Q151M RT mutant generated new hot spots, which were not
      observed for wild-type HIV-1 RT previously. The VILYM RT showed a marked
      reduction in error rate at two of the predominant mutational hot spots that have
      been observed for wild-type HIV-1 RT.

PMID- 9525608
TI  - Deletion of a CD2-like gene, 8-DR, from African swine fever virus affects viral
      infection in domestic swine.
AB  - An African swine fever virus (ASFV) gene with similarity to the T-lymphocyte
      surface antigen CD2 has been found in the pathogenic African isolate Malawi Lil
      20/1 (open reading frame [ORF] 8-DR) and a cell culture-adapted European virus,
      BA71V (ORF EP402R) and has been shown to be responsible for the hemadsorption
      phenomenon observed for ASFV-infected cells. The structural and functional
      similarities of the ASFV gene product to CD2, a cellular protein involved in cell
      cell adhesion and T-cell-mediated immune responses, suggested a possible role for
      this gene in tissue tropism and/or immune evasion in the swine host. In this
      study, we constructed an ASFV 8-DR gene deletion mutant (delta8-DR) and its
      revertant (8-DR.R) from the Malawi Lil-20/1 isolate to examine gene function in
      vivo. In vitro, delta8-DR, 8-DR.R, and the parental virus exhibited
      indistinguishable growth characteristics on primary porcine macrophage cell
      cultures. In vivo, 8-DR had no obvious effect on viral virulence in domestic
      pigs; disease onset, disease course, and mortality were similar for the mutant
      delta8-DR, its revertant 8-DR.R, and the parental virus. Altered viral infection
      was, however, observed for pigs infected with delta8-DR. A delay in spread to
      and/or replication of delta8-DR in the draining lymph node, a delay in
      generalization of infection, and a 100- to 1,000-fold reduction in virus titers
      in lymphoid tissue and bone marrow were observed. Onset of viremia for delta8-DR
      infected animals was significantly delayed (by 2 to 5 days), and mean viremia
      titers were reduced approximately 10,000-fold at 5 days postinfection and 30- to
      100-fold at later times; moreover, unlike in 8-DR.R-infected animals, the viremia
      was no longer predominantly erythrocyte associated but rather was equally
      distributed among erythrocyte, leukocyte, and plasma fractions. Mitogen-dependent
      lymphocyte proliferation of swine peripheral blood mononuclear cells in vitro was
      reduced by 90 to 95% following infection with 8-DR.R but remained unaltered
      following infection with delta8-DR, suggesting that 8-DR has immunosuppressive
      activity in vitro. Together, these results suggest an immunosuppressive role for
      8-DR in the swine host which facilitates early events in viral infection. This
      may be of most significance for ASFV infection of its highly adapted natural
      host, the warthog.

PMID- 9525610
TI  - Adenovirus preterminal protein binds to the CAD enzyme at active sites of viral
      DNA replication on the nuclear matrix.
AB  - Adenovirus (Ad) replicative complexes form at discrete sites on the nuclear
      matrix (NM) via an interaction mediated by the precursor of the terminal protein
      (pTP). The identities of cellular proteins involved in these complexes have
      remained obscure. We present evidence that pTP binds to a multifunctional
      pyrimidine biosynthesis enzyme found at replication domains on the NM. Far
      Western blotting identified proteins of 150 and 240 kDa that had pTP binding
      activity. Amino acid sequencing of the 150-kDa band revealed sequence identity to
      carbamyl phosphate synthetase I (CPS I) and a high degree of homology to the
      related trifunctional enzyme known as CAD (for carbamyl phosphate synthetase,
      aspartate transcarbamylase, and dihydroorotase). Western blotting with an
      antibody directed against CAD detected a 240-kDa band that comigrated with that
      detected by pTP far-Western blotting. Binding experiments showed that a pTP-CAD
      complex was immunoprecipitable from cell extracts in which pTP was expressed by a
      vaccinia virus recombinant. Additionally, in vitro-translated epitope-tagged pTP
      and CAD were immunoprecipitable as a complex, indicating the occurrence of a
      protein-protein interaction. Confocal fluorescence microscopy of Ad-infected NM
      showed that pTP and CAD colocalized in nuclear foci. Both pTP and CAD were
      confirmed to colocalize with active sites of replication detected by
      bromodeoxyuridine incorporation. These data support the concept that the pTP-CAD
      interaction may allow anchorage of Ad replication complexes in the proximity of
      required cellular factors and may help to segregate replicated and unreplicated
      viral DNA.

PMID- 9525611
TI  - A single amino acid change in the hemagglutinin protein of measles virus
      determines its ability to bind CD46 and reveals another receptor on marmoset B
      cells.
AB  - This paper provides evidence for a measles virus receptor other than CD46 on
      transformed marmoset and human B cells. We first showed that most tissues of
      marmosets are missing the SCR1 domain of CD46, which is essential for the binding
      of Edmonston measles virus, a laboratory strain that has been propagated in Vero
      monkey kidney cells. In spite of this deletion, the common marmoset was shown to
      be susceptible to infections by wild-type isolates of measles virus, although
      they did not support Edmonston measles virus production. As one would expect from
      these results, measles virus could not be propagated in owl monkey or marmoset
      kidney cell lines, but surprisingly, both a wild-type isolate (Montefiore 89) and
      the Edmonston laboratory strain of measles virus grew efficiently in B95-8
      marmoset B cells. In addition, antibodies directed against CD46 had no effect on
      wild-type infections of marmoset B cells and only partially inhibited the
      replication of the Edmonston laboratory strain in the same cells. A direct
      binding assay with insect cells expressing the hemagglutinin (H) proteins of
      either the Edmonston or Montefiore 89 measles virus strains was used to probe the
      receptors on these B cells. Insect cells expressing Edmonston H but not the wild
      type H bound to rodent cells with CD46 on their surface. On the other hand, both
      the Montefiore 89 H and Edmonston H proteins adhered to marmoset and human B
      cells. Most wild-type H proteins have asparagine residues at position 481 and can
      be converted to a CD46-binding phenotype by replacement of the residue with
      tyrosine. Similarly, the Edmonston H protein did not bind CD46 when its Tyr481
      was converted to asparagine. However, this mutation did not affect the ability of
      Edmonston H to bind marmoset and human B cells. The preceding results provide
      evidence, through the use of a direct binding assay, that a second receptor for
      measles virus is present on primate B cells.

PMID- 9525612
TI  - Characterization of the single-stranded DNA binding protein encoded by the
      vaccinia virus I3 gene.
AB  - The 34-kDa protein encoded by the I3 gene of vaccinia virus is expressed at early
      and intermediate times postinfection and is phosphorylated on serine residues.
      Recombinant I3 has been expressed in Escherichia coli and purified to near
      homogeneity, as has the protein from infected cells. Both recombinant and
      endogenous I3 protein demonstrate a striking affinity for single-stranded, but
      not for double-stranded, DNA. The interaction with DNA is resistant to salt,
      exhibits low cooperativity, and appears to involve a binding site of
      approximately 10 nucleotides. Electrophoretic mobility shift assays indicate that
      numerous I3 molecules can bind to a template, reflecting the stoichiometric
      interaction of I3 with DNA. Sequence analysis reveals that a pattern of aromatic
      and charged amino acids common to many replicative single-stranded DNA binding
      proteins (SSBs) is conserved in I3. The inability to isolate viable virus
      containing an interrupted I3 allele provides strong evidence that the I3 protein
      plays an essential role in the viral life cycle. A likely role for I3 as an SSB
      involved in DNA replication and/or repair is discussed.

PMID- 9525613
TI  - Increased induction of apoptosis by a Sendai virus mutant is associated with
      attenuation of mouse pathogenicity.
AB  - An avirulent mutant of Sendai virus, Ohita-MVC11 (MVC11), was generated from a
      highly virulent field strain, Ohita-M1 (M1), through successive passages in LLC
      MK2 cell cultures (M. Itoh, Y. Isegawa, H. Hotta, and M. Homma, J. Gen. Virol.
      78:3207-3215, 1997). In LLC-MK2 cells, MVC11 induced a high degree of apoptotic
      cell death that was demonstrated by chromatin condensation of the nucleus and DNA
      fragmentation, and production of MVC11 declined markedly after prolonged culture.
      On the other hand, M1 did not induce prominent apoptosis and maintained high
      virus titers. In primary mouse pulmonary epithelial cell cultures, M1 replicated
      rather slowly to reach maximum level of virus production at 3 days postinfection,
      and high levels of virus production were maintained thereafter without causing
      apoptosis. In contrast, MVC11, which produced 20 times more progeny virus than M1
      at 1 day postinfection, induced a high degree of apoptotic cell death before the
      virus replication cycle was completed. Accordingly, the production of progeny
      virus was strongly inhibited thereafter. In the lungs of mice infected with
      MVC11, virus antigens and signals of DNA fragmentation detected by the in situ
      terminal deoxynucleotidyltransferase-mediated dUTP nick end-labeling technique
      colocalized in bronchial epithelial cells, clearly demonstrating that infection
      by MVC11 triggered apoptosis in vivo as well as in vitro. These results suggest
      the possibility that induction of apoptosis by MVC11 plays an important role in
      attenuation of mouse pathogenicity by restricting progeny virus production in the
      lung. The C protein was shown to have the capacity to induce apoptosis, and the
      increased level of the C protein in MVC11-infected cells was considered to
      account partly, if not entirely, for the induction of apoptosis.

PMID- 9525615
TI  - Cytotoxic T-lymphocyte target proteins and their major histocompatibility complex
      class I restriction in response to adenovirus vectors delivered to mouse liver.
AB  - The activation of cytotoxic T lymphocytes (CTLs) to cells infected with
      adenovirus vectors contributes to problems of inflammation and transient gene
      expression that attend their use in gene therapy. The goal of this study was to
      identify in a murine model of liver gene therapy the proteins that provide
      targets to CTLs and to characterize the major histocompatibility complex (MHC)
      class I restricting elements. Mice of different MHC haplotypes were infected with
      an E1-deleted adenovirus expressing human alkaline phosphatase (ALP) or beta
      galactosidase as a reporter protein, and splenocytes were harvested for in vitro
      CTL assays to aid in the characterization of CTL epitopes. A library of vaccinia
      viruses was created to express individual viral open reading frames, as well as
      the ALP and lacZ transgenes. The MHC haplotype had a dramatic impact on the
      distribution of CTL targets: in C57BL/6 mice, the hexon protein presented by both
      H-2Kb and H2Db was dominant, and in C3H mice, H-2Dk-restricted presentation of
      ALP was dominant. Adoptive transfer of CTLs specific for various adenovirus
      proteins or transgene products into either Rag-I or C3H-scid mice infected
      previously with an E1-deleted adenovirus verified the in vivo relevance of the
      adenovirus-specific CTL targets identified in vitro. The results of these
      experiments illustrate the impact of lr gene control on the response to gene
      therapy with adenovirus vectors and suggest that the efficacy of therapy with
      adenovirus vectors may exhibit considerable heterogeneity when applied in human
      populations.

PMID- 9525614
TI  - Functional analysis of the human immunodeficiency virus type 1 Rev protein
      oligomerization interface.
AB  - The expression of human immunodeficiency virus type 1 (HIV-1) structural proteins
      requires the action of the viral trans-regulatory protein Rev. Rev is a nuclear
      shuttle protein that directly binds to its cis-acting Rev response element (RRE)
      RNA target sequence. Subsequent oligomerization of Rev monomers on the RRE and
      interaction of Rev with a cellular cofactor(s) result in the cytoplasmic
      accumulation of RRE-containing viral mRNAs. Moreover, Rev by itself is exported
      from the nucleus to the cytoplasm. Although it has been demonstrated that Rev
      multimerization is critically required for Rev activity and hence for HIV-1
      replication, the number of Rev monomers required to form a trans-activation
      competent complex on the RRE is unknown. Here we report a systematic analysis of
      the putative multimerization domains within the Rev trans-activator protein. We
      identify the amino acid residues which are part of the proposed single
      hydrophobic surface patch in the Rev amino terminus that mediates intermolecular
      interactions. Furthermore, we show that the expression of a multimerization
      deficient Rev mutant blocks HIV-1 replication in a trans-dominant (dominant
      negative) fashion.

PMID- 9525616
TI  - Recovery of a fully viable chimeric human parainfluenza virus (PIV) type 3 in
      which the hemagglutinin-neuraminidase and fusion glycoproteins have been replaced
      by those of PIV type 1.
AB  - The recent recovery of human parainfluenza virus type 3 (PIV3) from cDNA,
      together with the availability of a promising, highly characterized live
      attenuated PIV3 vaccine virus, suggested a novel strategy for the rapid
      development of comparable recombinant vaccine viruses for human PIV1 and PIV2.
      The strategy, illustrated here for PIV1, is to create chimeric viruses in which
      the two protective antigens, the hemagglutinin-neuraminidase (HN) and fusion (F)
      envelope glycoproteins, of an attenuated PIV3 variant are replaced by those of
      PIV1 or PIV2. As a first step, this has been achieved by using recombinant wild
      type (wt) PIV3 as the recipient for PIV1 HN and F, engineered so that each PIV1
      open reading frame is flanked by the existing PIV3 nontranslated regions and
      transcription signals. This yielded a viable chimeric recombinant virus,
      designated rPIV3-1, that encodes the PIV1 HN and F glycoproteins in the
      background of the wt PIV3 internal proteins. There were three noteworthy
      findings. First, in contrast to recently reported glycoprotein replacement
      chimeras of vesicular somatitis virus or measles virus, the PIV3-1 chimera
      replicates in LLC-MK2 cells and in the respiratory tract of hamsters as
      efficiently as its PIV1 and PIV3 parents. This is remarkable because the HN and F
      glycoproteins share only 43 and 47%, respectively, overall amino acid sequence
      identity between serotypes. In particular, the cytoplasmic tails share only 9 to
      11% identity, suggesting that their presumed role in virion morphogenesis does
      not involve sequence-specific contacts. Second, rPIV3-1 was found to possess
      biological properties derived from each of its parent viruses. Specifically, it
      requires trypsin for efficient plaque formation in tissue culture, like its PIV1
      parent but unlike PIV3. On the other hand, it causes an extensive cytopathic
      effect (CPE) in LLC-MK2 cultures which resembles that of its PIV3 parent but
      differs from that of its noncytopathic PIV1 parent. This latter finding indicates
      that the genetic basis for the CPE of PIV3 in tissue culture lies outside regions
      encoding the HN or F glycoprotein. Third, it should now be possible to rapidly
      develop a live attenuated PIV1 vaccine by the staged introduction of known,
      characterized attenuating mutations present in a live attenuated PIV3 vaccine
      candidate into the PIV3-1 cDNA followed by recovery of attenuated derivatives of
      rPIV3-1.

PMID- 9525617
TI  - Ubiquitin is covalently attached to the p6Gag proteins of human immunodeficiency
      virus type 1 and simian immunodeficiency virus and to the p12Gag protein of
      Moloney murine leukemia virus.
AB  - Host proteins are incorporated into retroviral virions during assembly and
      budding. We have examined three retroviruses, human immunodeficiency virus type 1
      (HIV-1), simian immunodeficiency virus (SIV), and Moloney murine leukemia virus
      (Mo-MuLV), for the presence of ubiquitin inside each of these virions. After a
      protease treatment to remove exterior viral as well as contaminating cellular
      proteins, the proteins remaining inside the virion were analyzed. The results
      presented here show that all three virions incorporate ubiquitin molecules at
      approximately 10% of the level of Gag found in virions. In addition to free
      ubiquitin, covalent ubiquitin-Gag complexes were detected, isolated, and
      characterized from all three viruses. Our immunoblot and protein sequencing
      results on treated virions showed that approximately 2% of either HIV-1 or SIV
      p6Gag was covalently attached to a single ubiquitin molecule inside the
      respective virions and that approximately 2 to 5% of the p12Gag in Mo-MuLV
      virions was monoubiquitinated. These results show that ubiquitination of Gag is
      conserved among these retroviruses and occurs in the p6Gag portion of the Gag
      polyprotein, a region that is likely to be involved in assembly and budding.

PMID- 9525618
TI  - Specific methylation patterns in two control regions of Epstein-Barr virus
      latency: the LMP-1-coding upstream regulatory region and an origin of DNA
      replication (oriP).
AB  - The Epstein-Barr virus (EBV) can establish at least four different forms of
      latent infection. Previously, we have shown that the level of methylation of the
      EBV genome varies, depending on the form of latency. The methylation status of
      CpGs was analyzed by the bisulfite genomic sequencing technique in four different
      cell types representing different forms of latency. The dyad symmetry element of
      the origin of replication (oriP) region and the latent membrane protein 1 (LMP-1)
      regulatory sequence (LRS) were studied. The dyad symmetry element has four
      binding sites for EBNA-1. In a cell with type I latency, a region upstream of the
      dyad symmetry element was highly methylated, whereas the dyad symmetry element
      was unmethylated in the EBNA-1-binding region. The LRS was extensively methylated
      in the LMP-1-negative cell line Rael, in contrast to a LMP-1-expressing
      nasopharyngeal carcinoma tumor (NPC C15), which was almost completely
      unmethylated. The methylation pattern of LRS in type I and type III Burkitt
      lymphoma cells of similar parental origins confirmed that demethylation of some
      regions takes place upon phenotypic drift.

PMID- 9525619
TI  - Adenovirus type 5 E4 open reading frame 4 protein induces apoptosis in
      transformed cells.
AB  - Adenovirus type 5 E4 open reading frame 4 (E4orf4) protein has been previously
      shown to counteract transactivation of the junB and c-fos genes by cyclic AMP
      plus E1A protein and to interact with protein phosphatase 2A (PP2A). Here, we
      show that the wild-type E4orf4 protein induces apoptosis in the E1A-expressing
      293 cells, in NIH 3T3 cells transformed with v-Ras, and in the lung carcinoma
      cell line H1299. The induction of apoptosis is not accompanied by enhanced levels
      of p53 in 293 cells and occurs in the absence of p53 in H1299 cells, indicating
      involvement of a p53-independent pathway. A mutant E4orf4 protein that had lost
      the ability to induce apoptosis also lost its ability to bind PP2A. We suggest
      that E4orf4 antagonizes continuous signals to proliferate, like those given by
      E1A or v-Ras, and that the conflicting signals lead to the induction of cell
      death.

PMID- 9525620
TI  - A leucine zipper-like domain is essential for dimerization and encapsidation of
      bluetongue virus nucleocapsid protein VP4.
AB  - The bluetongue virus (BTV) minor protein VP4, with molecular mass of 76 kDa, is
      one of the seven structural proteins and is located within the inner capsid of
      the virion. The protein has a putative leucine zipper near the carboxy terminus
      of the protein. In this study, we have investigated the functional activity of
      this putative leucine zipper by a number of approaches. The putative leucine
      zipper region (amino acids [aa] 523 to 551) was expressed initially as a fusion
      protein by using the pMAL vector of Escherichia coli, which expresses a maltose
      binding monomeric protein. The expressed fusion protein was purified by affinity
      chromatography, and its size was determined by gel filtration chromatography.
      Proteins of two sizes, 51 and 110 kDa, were recovered, one equivalent to the
      monomeric form and the other equivalent to the dimeric form of the fusion
      protein. To prove that the VP4-derived sequence was responsible for dimerization
      of this protein, a mutated fusion protein was created in which a VP4 leucine
      residue (at aa 537) within the zipper was replaced by a proline residue. Analyses
      of the mutated protein demonstrated that the single mutation indeed prevented
      dimerisation of the protein. The dimeric nature of VP4 was further confirmed by
      using purified full-length BTV-10 VP4 recovered from recombinant baculovirus
      expressing BTV-10 VP4-infected insect cells. Using chemical cross-linking and gel
      filtration chromatography, we documented that the native VP4 indeed exists as a
      dimer in solution. Subsequently, Leu537 was replaced by either a proline or an
      alanine residue and the full-length mutated VP4 was expressed in the baculovirus
      system. By sucrose density gradient centrifugation and gel filtration
      chromatography, these mutant forms of VP4 were shown to lack the ability to form
      dimers. The biological significance of the dimeric forms of VP4 was examined by
      using a functional assay system, in which the encapsidation activity of VP4 into
      core-like particles (CLPs) was studied (H. LeBlois, T. French, P. P. C. Mertens,
      J. N. Burroughs, and P. Roy, Virology 189:757-761, 1992). We demonstrated
      conclusively that dimerization of VP4 was essential for encapsidation by CLPs.

PMID- 9525621
TI  - In vitro transcription of pe38/polyhedrin hybrid promoters reveals sequences
      essential for recognition by the baculovirus-induced RNA polymerase and for the
      strength of very late viral promoters.
AB  - In vitro transcription was used to analyze the promoter specificity of the alpha
      amanitin-resistant RNA polymerase that is induced late during infection of
      Autographa californica multicapsid nuclear polyhedrosis virus. By modifying the
      preparation of crude nuclear extracts, we have established an assay that permits
      differentiation between weak late and strong very late viral promoters. The virus
      induced RNA polymerase initiates at a TAAG sequence motif in both late and very
      late promoters. Based on the sensitivity of our in vitro transcription system, we
      have investigated the sequences responsible for a functional TAAG motif and their
      putative role with respect to the strength of very late promoters. By
      constructing hybrid promoters between the early pe38 and the very late polyhedrin
      promoters, we demonstrated that the replacement of 7 nucleotides upstream of the
      nonfunctional TAAG sequences in the pe38 promoter with the corresponding
      sequences of the polyhedrin promoter was sufficient for recognition by the virus
      induced RNA polymerase. The strength of the very late polyhedrin promoter was
      established after replacing the 5' untranslated sequences of the pe38 promoter by
      those of the polyhedrin promoter in addition to the 7 nucleotides upstream of the
      TAAG motif.

PMID- 9525622
TI  - Expression of enzymatically active rabbit hemorrhagic disease virus RNA-dependent
      RNA polymerase in Escherichia coli.
AB  - The rabbit hemorrhagic disease virus (RHDV) (isolate AST/89) RNA-dependent RNA
      polymerase (3Dpol) coding region was expressed in Escherichia coli by using a
      glutathione S-transferase-based vector, which allowed milligram purification of a
      homogeneous enzyme with an expected molecular mass of about 58 kDa. The
      recombinant polypeptide exhibited rifampin- and actinomycin D-resistant, poly(A)
      dependent poly(U) polymerase. The enzyme also showed RNA polymerase activity in
      in vitro reactions with synthetic RHDV subgenomic RNA in the presence or absence
      of an oligo(U) primer. Template-size products were synthesized in the oligo(U)
      primed reactions, whereas in the absence of added primer, RNA products up to
      twice the length of the template were made. The double-length RNA products were
      double stranded and hybridized to both positive- and negative-sense probes.

PMID- 9525624
TI  - Human parvovirus B19 nonstructural (NS1) protein induces apoptosis in erythroid
      lineage cells.
AB  - Infection of erythroid-lineage cells by human parvovirus B19 is characterized by
      a gradual cytocidal effect. Accumulating evidence now implicates the
      nonstructural (NS1) protein of the virus in cytotoxicity, but the mechanism
      underlying the NS1-induced cell death is not known. Using a stringent regulatory
      system, we demonstrate that NS1 cytotoxicity is closely related to apoptosis, as
      evidenced by cell morphology, genomic DNA fragmentation, and cell cycle analysis
      with the human erythroleukemia cell line K562 and the erythropoietin-dependent
      megakaryocytic cell line UT-7/Epo. Apoptosis was significantly inhibited by an
      interleukin-1beta (IL-1beta)-converting enzyme (ICE)/CED-3 family protease
      inhibitor, Ac-DEVD-CHO (CPP32; caspase 3), whereas a similar inhibitor of ICE
      (caspase 1), Ac-YVAD-CHO, had no effect. Furthermore, stable expression of the
      human Bcl-2 proto-oncogene resulted in near-total protection from cell death in
      response to NS1 induction. Mutations engineered into the nucleoside triphosphate
      binding domain of NS1 significantly rescued cells from NS1-induced apoptosis
      without having any effect on NS1-induced activation of the IL-6 gene expression
      which is mediated by NF-kappaB. Furthermore, using pentoxifylline, an inhibitor
      of NF-kappaB activation, we demonstrate that the NF-kappaB-mediated IL-6
      activation by NS1 is uncoupled from the apoptotic pathway. This functional
      dissection indicates a complexity underlying the biochemical function of human
      parvovirus NS1 in transcriptional activation and induction of apoptosis. Our
      findings indicate that NS1 of parvovirus B19 induces cell death by apoptosis in
      at least erythroid-lineage cells by a pathway that involves caspase 3, whose
      activation may be a key event during NS1-induced cell death.

PMID- 9525625
TI  - Bovine herpesvirus 1 glycoprotein M forms a disulfide-linked heterodimer with the
      U(L)49.5 protein.
AB  - Nine glycoproteins (gB, gC, gD, gE, gG, gH, gI, gK, and gL) have been identified
      in bovine herpesvirus 1 (BHV-1). gM has been identified in many other alpha-,
      beta-, and gammaherpesviruses, in which it appears to play a role in membrane
      penetration and cell-to-cell fusion. We sought to express BHV-1 open reading
      frame U(L)10, which encodes gM, and specifically identify the glycoprotein. We
      corrected a frameshift error in the published sequence and used the corrected
      sequence to design coterminal peptides from the C terminus. These were expressed
      as glutathione S-transferase fusion proteins in Escherichia coli. The fusion
      protein containing the 63 C-terminal amino acids from the corrected gM sequence
      engendered antibodies that immunoprecipitated a 30-kDa protein from in vitro
      translation reactions programmed with the U(L)10 gene. Proteins
      immunoprecipitated by this antibody from virus-infected cells ran at 36 and 43
      kDa in reducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS
      PAGE) and 43 and 48 kDa in nonreducing SDS-PAGE. Only the larger of the pair was
      present in virions. A 7-kDa protein was released from gM by reducing agents. The
      7-kDa protein was not recognized in Western blots probed with the anti-gM
      antibody but reacted specifically with antibodies prepared against BHV-1
      U(L)49.5, previously reported to be a 9-kDa protein associated with an
      unidentified 39-kDa protein (X. Liang, B. Chow, C. Raggo, and L. A. Babiuk, J.
      Virol. 70:1448-1454, 1996). This is the first report of a small protein
      covalently bound to any herpesvirus gM. Similar patterns of hydrophobic domains
      and cysteines in all known gM and U(L)49.5 homologs suggest that these two
      proteins may be linked by disulfide bonds in all herpesviruses.

PMID- 9525626
TI  - Human immunodeficiency virus type 1 (HIV-1) viral protein R (Vpr) interacts with
      Lys-tRNA synthetase: implications for priming of HIV-1 reverse transcription.
AB  - The vpr gene of human immunodeficiency virus type 1 (HIV-1) encodes a 96-amino
      acid 14-kDa protein (viral protein R [Vpr]), which is produced late in the viral
      life cycle and is incorporated into the virion. Although Vpr is not required for
      viral replication in transformed cell lines and primary T lymphocytes, it is
      essential for productive infection of macrophages and monocytes and appears to be
      important for pathogenesis in vivo. To establish the role of Vpr in HIV-1
      replication and pathogenesis, we have isolated cellular proteins with which Vpr
      interacts. By using the yeast two-hybrid system, Lys-tRNA synthetase (LysRS) was
      identified as a Vpr-interacting protein. The interaction between Vpr and LysRS
      was characterized both in vitro and in vivo, and the domains of Vpr required for
      the interaction were defined. In the presence of Vpr, LysRS-mediated amino
      acylation of tRNA(Lys) is inhibited. Since tRNA(Lys) is the primer for reverse
      transcription of the HIV-1 genome, this suggests that the interaction between Vpr
      and LysRS may influence the initiation of HIV-1 reverse transcription.

PMID- 9525623
TI  - Extensive diversification of human immunodeficiency virus type 1 subtype B
      strains during dual infection of a chimpanzee that progressed to AIDS.
AB  - A chimpanzee (C-499) infected for more than 9 years with two subtype B isolates
      of human immunodeficiency virus type 1 (HIV-1), one (HIV-1(SF2)) that replicates
      poorly and one (HIV-1(LAV-1b)) that replicates efficiently in chimpanzees, died
      of AIDS 11 years after initial infection (F. J. Novembre et al., J. Virol.
      71:4086-4091, 1997). Nucleotide sequence and phylogenetic analyses of the C2 to
      V5 region of env (C2-V5env) in proviral DNA from peripheral blood lymphocytes
      obtained 22 months before death revealed two distinct virus populations. One of
      these populations appeared to be a recombinant in env, having the V3 loop from
      HIV-1(SF2) and the V4-V5 region from HIV-1(LAV-1b); the other population had
      evolved from HIV-1(LAV-1b). In addition to C2-V5env, the entire p17gag and nef
      genes were sequenced; however, based on nucleotide sequences and phylogeny,
      whether the progenitor of the p17gag and nef genes was SF2 or LAV-1b could not be
      determined. Compared to the two original viruses, the divergence of all clones of
      C2-V5env ranged from 9.37 to 20.2%, that of p17gag ranged from 3.11 to 9.29%, and
      that of nef ranged from 4.02 to 7.9%. In contrast, compared to the maximum
      variation of 20.2% in C2-V5env for C-499, the maximum diversities in C2-V5env in
      proviruses from two chimpanzees infected with HIV-1(LAV-1b) for 9 and 10 years
      were 9.65 and 2.48%, respectively. These results demonstrate that (i) two
      distinct HIV-1 populations can coexist and undergo extensive diversification in
      chimpanzees with progressive HIV-1-induced disease and (ii) recombination between
      two subtype B strains occurred even though the second strain was inoculated 15
      months after the first one. Furthermore, evaluation of env genes from three
      chimpanzees infected with the same strain suggests that the magnitude of HIV-1
      diversification could be related to higher viral burdens, manifestations of
      disease, and/or dual infection.

PMID- 9525627
TI  - Herpes simplex virus DNA cleavage and packaging: association of multiple forms of
      U(L)15-encoded proteins with B capsids requires at least the U(L)6, U(L)17, and
      U(L)28 genes.
AB  - The U(L)15 gene of herpes simplex virus (HSV) is one of several genes required
      for the packaging of viral DNA into intranuclear B capsids to produce C capsids
      that become enveloped at the inner nuclear membrane. A rabbit antiserum directed
      against U(L)15-encoded protein recognized three proteins with apparent Mrs of
      79,000, 80,000, and 83,000 in highly purified B capsids. The 83,000-Mr protein
      was detected in type C capsids and comigrated with the product of a U(L)15 cDNA
      transcribed and translated in vitro. The 83,000- and 80,000-Mr proteins were
      readily detected in purified virions. Inasmuch as (i) none of these proteins were
      detectable in capsids purified from cells infected with HSV-1(deltaU(L)15), a
      virus lacking an intact U(L)15 gene, and (ii) corresponding proteins in capsids
      purified from cells infected with a recombinant virus [HSV-1(R7244), containing a
      20-codon tag at the 3' end of U(L)15] were decreased in electrophoretic mobility
      relative to the wild-type proteins, we conclude that the proteins with apparent
      Mrs of 83,000, 80,000, and 79,000 are products of U(L)15 with identical C
      termini. The 79,000-, 80,000-, and 83,000-Mr proteins remained associated with B
      capsids in the presence of 0.5 M guanidine HCl and remained detectable in capsids
      treated with 2.0 M guanidine HCl and lacking proteins associated with the capsid
      core. These data, therefore, indicate that U(L)15-encoded proteins are integral
      components of B capsids. Only the 83,000-Mr protein was detected in B capsids
      purified from cells infected with viruses lacking the U(L)6, U(L)17, or U(L)28
      genes, which are required for DNA cleavage and packaging, suggesting that capsid
      association of the 80,000- and 79,000-Mr proteins requires intact cleavage and
      packaging machinery. These data, therefore, indicate that capsid association of
      the 80,000- and 79,000-Mr U(L)15-encoded proteins reflects a previously
      unrecognized step in the DNA cleavage and packaging reaction.

PMID- 9525628
TI  - Cleavage of the feline calicivirus capsid precursor is mediated by a virus
      encoded proteinase.
AB  - Feline calicivirus (FCV), a member of the Caliciviridae, produces its major
      structural protein as a precursor polyprotein from a subgenomic-sized mRNA. In
      this study, we show that the proteinase responsible for processing this precursor
      into the mature capsid protein is encoded by the viral genome at the 3'-terminal
      portion of open reading frame 1 (ORF1). Protein expression studies of either the
      entire or partial ORF1 indicate that the proteinase is active when expressed
      either in in vitro translation or in bacterial cells. Site-directed mutagenesis
      was used to characterize the proteinase Glu-Ala cleavage site in the capsid
      precursor, utilizing an in vitro cleavage assay in which mutant precursor
      proteins translated from cDNA clones were used as substrates for trans cleavage
      by the proteinase. In general, amino acid substitutions in the P1 position (Glu)
      of the cleavage site were less well tolerated by the proteinase than those in the
      P1' position (Ala). The precursor cleavage site mutations were introduced into an
      infectious cDNA clone of the FCV genome, and transfection of RNA derived from
      these clones into feline kidney cells showed that efficient cleavage of the
      capsid precursor by the virus-encoded proteinase is a critical determinant in the
      growth of the virus.

PMID- 9525629
TI  - Hepatitis C virus core from two different genotypes has an oncogenic potential
      but is not sufficient for transforming primary rat embryo fibroblasts in
      cooperation with the H-ras oncogene.
AB  - Persistent infection with hepatitis C virus (HCV) is associated with the
      development of liver cirrhosis and hepatocellular carcinoma. To examine the
      oncogenic potential of the HCV core gene product, primary rat embryo fibroblasts
      (REFs) were transfected with the core gene in the presence or absence of the H
      ras oncogene. In contrast to a previous report (R. B. Ray, L. M. Lagging, K.
      Meyer, and R. Ray, J. Virol. 70:4438-4443, 1996), HCV core proteins from two
      different genotypes (type 1a and type 1b) were not found to transform REFs to
      tumorigenic phenotype in cooperation with the H-ras oncogene, although the core
      protein was successfully expressed 20 days after transfection. In addition, REFs
      transfected with E1A- but not core-expressing plasmid showed the phenotype of
      immortalized cells when selected with G418. The biological activity was confirmed
      by observing the transcription activation from two viral promoters, Rous sarcoma
      virus long terminal repeat and simian virus 40 promoter, which are known to be
      activated by the core protein from HCV-1 isolate. In contrast to the result with
      primary cells, the Rat-1 cell line, stably expressing HCV core protein, exhibited
      focus formation, anchorage-independent growth, and tumor formation in nude mice.
      HCV core protein was able to induce the transformation of Rat-1 cells with
      various efficiencies depending on the expression level of the core protein. These
      results indicate that HCV core protein has an oncogenic potential to transform
      the Rat-1 cell line but is not sufficient to either immortalize primary REFs by
      itself or transform primary cells in conjunction with the H-ras oncogene.

PMID- 9525630
TI  - A novel membrane protein is a mouse mammary tumor virus receptor.
AB  - Mouse mammary tumor virus (MMTV) infects a number of different cell types,
      including mammary gland and lymphoid cells, in vivo. To identify the cellular
      receptor for this virus, a mouse cDNA expression library was transfected into Cos
      7 monkey kidney cells, and those transfected cells able to bind virus were
      selected by using antibody against the virus's cell surface envelope protein,
      gp52. One clone isolated from a library prepared from newborn thymus RNA, called
      MTVR, was able to confer virus binding to both monkey and human cells; this
      binding was blocked by anti-MTVR antibody. Moreover, transfection of MTVR into
      CV1 cells rendered them susceptible to infection by a murine leukemia virus-based
      retrovirus vector pseudotyped with the MMTV envelope protein. An epitope-tagged
      MTVR cofractionated with cellular membranes. Coimmunoprecipitation of the MMTV
      envelope protein and a MTVR-rabbit Fc fusion protein showed that these two
      proteins bound to each other. The MTVR sequence clone is unique, shows no
      homology to known membrane proteins, and is transcribed in many tissues.

PMID- 9525631
TI  - Detection of hepatitis G virus replication sites by using highly strand-specific
      Tth-based reverse transcriptase PCR.
AB  - The replication sites of the recently discovered hepatitis G virus (HGV) remain
      unknown. Using highly strand-specific Tth-based reverse transcriptase PCR, we
      searched for the presence of viral RNA negative strand in multiple autopsy
      tissues from four patients with AIDS and in peripheral blood mononuclear cells
      from six other human immunodeficiency virus-positive patients. Negative-strand
      HGV RNA was detected in three of four bone marrow samples, in two of two spleen
      samples, and in one of four liver tissue samples. However, the specific cellular
      site of replication within the positive tissues was not determined. This study
      does not support HGV as a primary hepatotropic virus.

PMID- 9525632
TI  - Neutralizing antibodies protect against lethal flavivirus challenge but allow for
      the development of active humoral immunity to a nonstructural virus protein.
AB  - Antibody-mediated neutralization of viruses has been extensively studied in
      vitro, but the precise mechanisms that account for antibody-mediated protection
      against viral infection in vivo still remain largely uncharacterized. The two
      points under discussion are antibodies conferring sterilizing immunity by
      neutralizing the virus inoculum or protection against the development of disease
      without complete inhibition of virus replication. For tick-borne encephalitis
      virus (TBEV), a flavivirus, transfer of neutralizing antibodies specific for
      envelope glycoprotein E protected mice from subsequent TBEV challenge.
      Nevertheless, short-term, low-level virus replication was detected in these mice.
      Furthermore, mice that were exposed to replicating but not to inactivated virus
      while passively protected developed active immunity to TBEV rechallenge. Despite
      the priming of TBEV-specific cytotoxic T cells, adoptive transfer of serum but
      not of T cells conferred immunity upon naive recipient mice. These transferred
      sera were not neutralizing and were predominantly specific for NS1, a
      nonstructural TBEV protein which is expressed in and on infected cells and which
      is also secreted from these cells. Results of these experiments showed that
      despite passive protection by neutralizing antibodies, limited virus replication
      occurs, indicating protection from disease rather than sterilizing immunity. The
      protective immunity induced by replicating virus is surprisingly not T-cell
      mediated but is due to antibodies against a nonstructural virus protein absent
      from the virion.

PMID- 9525633
TI  - Type C retrovirus released from porcine primary peripheral blood mononuclear
      cells infects human cells.
AB  - As part of the evaluation of porcine cells, tissues, and organs intended for
      transplantation into humans, we investigated the conditions required to induce
      expression and release of porcine endogenous retrovirus (PoEV) from primary
      cells. Pigs contain endogenous retroviral sequences encoding infectious
      retrovirus, yet little is known about the conditions required to activate the
      expression and release of PoEV from primary cells. We show here that mitogenic
      activation of peripheral blood mononuclear cells (PBMC) isolated from the
      National Institutes of Health (NIH) miniature pig and the Yucatan pig resulted in
      the activation and release of an infectious type C retrovirus. Coculture of
      activated porcine PBMC with pig or human cell lines resulted in the transfer and
      expression of PoEV-specific sequences and the establishment of a productive
      infection. Sequence comparison of portions of the PoEV pol gene expressed in pig
      cell lines productively infected with virus derived from NIH miniature pig and
      Yucatan pig PBMC revealed marked similarity, suggesting that one or a few loci
      may be capable of being activated to yield an infectious virus. These findings
      demonstrate that the presence of endogenous viruses in source animals needs to be
      carefully considered when the infectious disease potential of xenotransplantation
      is being assessed.

PMID- 9525634
TI  - Viruses and cells with mutations affecting viral entry are selected during
      persistent rotavirus infections of MA104 cells.
AB  - To better understand mechanisms of persistent rotavirus infections of cultured
      cells, we established independent, persistently infected cultures of MA104 cells,
      using rotavirus strain SA11. The cultures were either passaged when the cells
      reached confluence or supplemented with fresh medium every 7 days. Viral titers
      in culture lysates varied from 10(4) to 10(7) PFU per ml during 350 days of
      culture maintenance. Trypan blue staining indicated that 72 to 100% of cells in
      the cultures were viable, and immunocytochemical staining using a monoclonal
      antibody directed against viral protein VP6 demonstrated that 38 to 63% of the
      cells contained rotavirus antigen. We tested the capacity of rotaviruses isolated
      from the persistently infected cultures (PI viruses) to infect cells cured of
      persistent infection. Although wild-type (wt) and PI viruses produced equivalent
      yields in parental MA104 cells, PI viruses produced greater yields than wt virus
      in cured cells, which indicates that viruses and cells coevolve during persistent
      rotavirus infections of MA104 cells. To determine whether mutations in viruses
      and cells selected during these persistent infections affect viral entry, we
      tested the effect of trypsin treatment of the viral inoculum on growth of wt and
      PI viruses. Trypsin pretreatment is required for postattachment penetration of
      rotavirus virions into cells. In contrast to the case with wt virus, PI viruses
      produced equivalent yields with and without trypsin pretreatment in parental
      MA104 cells. However, PI viruses required trypsin pretreatment for efficient
      growth in cured cells. These results indicate that mutant viruses and cells are
      selected during maintenance of persistent rotavirus infections of MA104 cells and
      suggest that mutations in each affect trypsin-dependent steps in rotavirus entry.

PMID- 9525635
TI  - Type D retrovirus capsid assembly and release are active events requiring ATP.
AB  - Mason-Pfizer monkey virus (M-PMV), the prototype type D retrovirus, differs from
      most other retroviruses by assembling its Gag polyproteins into procapsids in the
      cytoplasm of infected cells. Once assembled, the procapsids migrate to the plasma
      membrane, where they acquire their envelope during budding. Because the processes
      of M-PMV protein transport, procapsid assembly, and budding are temporally and
      spatially unlinked, we have been able to determine whether cellular proteins play
      an active role during the different stages of procapsid morphogenesis. We report
      here that at least two stages of morphogenesis require ATP. Both procapsid
      assembly and procapsid transport to the plasma membrane were reversibly blocked
      by treating infected cells with sodium azide and 2-deoxy-D-glucose, which we show
      rapidly and reversibly depletes cellular ATP pools. Assembly of procapsids in
      vitro in a cell-free translation/assembly system was inhibited by the addition of
      nonhydrolyzable ATP analogs, suggesting that ATP hydrolysis and not just ATP
      binding is required. Since retrovirus Gag polyproteins do not bind or hydrolyze
      ATP, these results demonstrate that cellular components must play an active role
      during retrovirus morphogenesis.

PMID- 9525636
TI  - Bombyx mori nucleopolyhedrovirus encodes a DNA-binding protein capable of
      destabilizing duplex DNA.
AB  - A DNA-binding protein (designated DBP) with an apparent molecular mass of 38 kDa
      was purified to homogeneity from BmN cells (derived from Bombyx mori) infected
      with the B. mori nucleopolyhedrovirus (BmNPV). Six peptides obtained after
      digestion of the isolated protein with Achromobacter protease I were partially or
      completely sequenced. The determined amino acid sequences indicated that DBP was
      encoded by an open reading frame (ORF16) located at nucleotides (nt) 16189 to
      17139 in the BmNPV genome (GenBank accession no. L33180). This ORF (designated
      dbp) is a homolog of Autographa californica multicapsid NPV ORF25, whose product
      has not been identified. BmNPV DBP is predicted to contain 317 amino acids
      (calculated molecular mass of 36.7 kDa) and to have an isoelectric point of 7.8.
      DBP showed a tendency to multimerization in the course of purification and was
      found to bind preferentially to single-stranded DNA. When bound to
      oligonucleotides, DBP protected them from hydrolysis by phage T4 DNA polymerase
      associated 3'-->5' exonuclease. The sizes of the protected fragments indicated
      that a binding site size for DBP is about 30 nt per protein monomer. DBP, but not
      BmNPV LEF-3, was capable of unwinding partial DNA duplexes in an in vitro system.
      This helix-destabilizing ability is consistent with the prediction that DBP
      functions as a single-stranded DNA binding protein in virus replication.

PMID- 9525637
TI  - The activity of Sendai virus genomic and antigenomic promoters requires a second
      element past the leader template regions: a motif (GNNNNN)3 is essential for
      replication.
AB  - The paramyxovirus genome, a nonsegmented, negative-polarity, single-stranded RNA
      of approximately 15 kb, contains six transcription units flanked at the 3' and 5'
      ends by a short (approximately 50- to 60-nucleotide) extracistronic sequence,
      dubbed the positive and negative leader regions. These leader template regions,
      present at the 3' end of the genome and the antigenome, have been shown to
      contain essential signals governing RNA replication activity. Whether they are
      sufficient to promote replication is still open to question. By using a series of
      Sendai virus defective interfering RNAs carrying a nested set of deletions in the
      promoter regions, it is shown here that for both the genomic and antigenomic
      promoters, a 3'-end RNA sequence of 96 nucleotides is required to allow
      replication. Sequence comparison of active and inactive promoters led to the
      identification of a set of three nucleotide hexamers (nucleotides 79 to 84, 85 to
      90, and 91 to 96) containing a repeated motif RXXYXX [shown as 5'-3' positive
      strand]. Sequential mutation of each hexamer into its complementary sequence
      confirmed their essential role. The three hexamers are required, and their
      relative positioning is important, since displacing them by 6 nucleotides
      destroyed promoter function. RNAs carrying degenerate nucleotides in the three
      hexamers were used as replication templates. They led to the selection of
      actively replicating RNA species exclusively carrying the basic motif (GNNNNN)3
      from nucleotides 79 to 96. These results clearly show that, apart from the region
      from nucleotides 1 to 31, previously identified as governing Sendai virus
      replication activity, a second element, spanning at the most nucleotides 79 to
      96, appears essential. Thus, the paramyxovirus replication promoters are not
      confined to the leader template regions, as seems to be the case for the
      rhabdoviruses.

PMID- 9525638
TI  - CBF, Myb, and Ets binding sites are important for activity of the core I element
      of the murine retrovirus SL3-3 in T lymphocytes.
AB  - Transcriptional enhancers within the long terminal repeats of murine leukemia
      viruses are major determinants of the pathogenic properties of these viruses.
      Mutations were introduced into the adjacent binding sites for three transcription
      factors within the enhancer of the T-cell-lymphomagenic virus SL3-3. The sites
      that were tested were, in 5'-to-3' order, a binding site for core binding factor
      (CBF) called core II, a binding site for c-Myb, a site that binds members of the
      Ets family of factors, and a second CBF binding site called core I. Mutation of
      each site individually reduced transcriptional activity in T lymphocytes.
      However, mutation of the Myb and core I binding sites had larger effects than
      mutation of the Ets or core II site. The relative effects on transcription in T
      cells paralleled the effects of the same mutations on viral lymphomagenicity,
      consistent with the idea that the role of these sequences in viral
      lymphomagenicity is indeed to regulate transcription in T cells. Mutations were
      also introduced simultaneously into multiple sites in the SL3-3 enhancer. The
      inhibitory effects of these mutations indicated that the transcription factor in
      T cells that recognizes the core I element of SL3-3, presumably CBF, needed to
      synergize with one or more factors bound at the upstream sites to function. This
      was tested further by generating a multimer construct that contained five tandem
      core I elements linked to a basal long terminal repeat promoter. This construct
      was inactive in T cells. However, transcriptional activity was detected with a
      multimer construct in which the transcription factor binding sites upstream of
      the core were also present. These results are consistent with the hypothesis that
      CBF requires heterologous transcription factors bound at nearby sites to function
      in T cells.

PMID- 9525639
TI  - Herpesvirus saimiri transforms human T-cell clones to stable growth without
      inducing resistance to apoptosis.
AB  - Herpesvirus saimiri (HVS) transforms human T cells to stable growth in vitro.
      Since HVS codes for two different antiapoptotic proteins, growth transformation
      by HVS might be expected to confer resistance to apoptosis. We found that the
      expression of both viral antiapoptotic genes was restricted to cultures with
      viral replication and absent in growth-transformed human T cells. A comparative
      examination of HVS-transformed T-cell clones and their native parental clones
      revealed that the expression of Bcl-2, Bcl-X(L), Bax, and members of the tumor
      necrosis factor receptor (TNF-R) superfamily with a death domain, namely, TNF-RI,
      CD95, and TRAMP, were not modulated by HVS. Expression of CD30 was induced in HVS
      transformed T cells, and these cells also expressed the CD30 ligand. Uninfected
      and transformed T cells were sensitive to CD95 ligation but resistant to
      apoptosis mediated by TRAIL or soluble TNF-alpha. CD95 ligand was constitutively
      expressed on transformed but not uninfected parental T cells. Both cell types
      showed similar sensitivity to cell death induction or inhibition of T-cell
      activation mediated by irradiation, oxygen radicals, dexamethasone, cyclosporine,
      and prostaglandin E2. Altogether, this study strongly suggests that growth
      transformation by HVS is based not on resistance to apoptosis but, rather, on
      utilization of normal cellular activation pathways.

PMID- 9525640
TI  - Adenovirus E1B 55K represses p53 activation in vitro.
AB  - Adenovirus E1B 55K protein cooperates with E1A gene products to induce cell
      transformation. E1B 55K mediates its effects by binding to and inhibiting the
      transcriptional activation and growth-suppression functions of the tumor
      suppressor p53. Previous studies in vivo have suggested that E1B 55K has an
      active role in repressing p53 transcriptional activation and that this repression
      function is directed to specific promoters through E1B 55K's interaction with DNA
      bound p53. Flag-tagged E1B 55K (e55K) was expressed with the baculovirus
      expression system and immunopurified. Gel filtration, velocity sedimentation
      centrifugation, and glutaraldehyde cross-linking indicated that e55K is a dimer
      with a nonglobular conformation. e55K bound directly to purified p53, causing an
      approximately 10-fold increase in p53 affinity for tandem binding sites. Using in
      vitro transcription assays reconstituted with purified p53, e55K, and HeLa cell
      nuclear extracts, we found that e55K specifically repressed p53 activation. These
      results demonstrate that as postulated from earlier transient expression
      experiments, E1B 55K is a specific repressor of transcription from a promoter
      with bound p53. Since HeLa nuclear extracts contain little detectable histone
      protein, E1B 55K probably represses transcription through direct or indirect
      interactions with the RNA polymerase II transcription machinery.

PMID- 9525641
TI  - Characterization of Ebola virus entry by using pseudotyped viruses:
      identification of receptor-deficient cell lines.
AB  - Studies analyzing Ebola virus replication have been severely hampered by the
      extreme pathogenicity of this virus. To permit analysis of the host range and
      function of the Ebola virus glycoprotein (Ebo-GP), we have developed a system for
      pseudotyping these glycoproteins into murine leukemia virus (MLV). This
      pseudotyped virus, MLV(Ebola), can be readily concentrated to titers which exceed
      5 x 10(6) infectious units/ml and is effectively neutralized by antibodies
      specific for Ebo-GP. Analysis of MLV(Ebola) infection revealed that the host
      range conferred by Ebo-GP is very broad, extending to cells of a variety of
      species. Notably, all lymphoid cell lines tested were completely resistant to
      infection; we speculate that this is due to the absence of a cellular receptor
      for Ebo-GP on B and T cells. The generation of high-titer MLV(Ebola) pseudotypes
      will be useful for the analysis of immune responses to Ebola virus infection,
      development of neutralizing antibodies, analysis of glycoprotein function, and
      isolation of the cellular receptor(s) for the Ebola virus.

PMID- 9525642
TI  - Progression to the G1b phase of the cell cycle is required for completion of
      human immunodeficiency virus type 1 reverse transcription in T cells.
AB  - Successful infection by human immunodeficiency virus type 1 (HIV-1) requires the
      activation of target cells. Infection of quiescent peripheral CD4 lymphocytes by
      HIV-1 results in incomplete, labile, reverse transcripts. In the present study,
      we isolated highly purified quiescent T cells and utilized the CD3/CD28
      activation pathways as well as cell cycle inhibitors to further define the role
      of costimulation and cell cycle progression in HIV-1 reverse transcription.
      Activation with alphaCD3 alone resulted in cell cycle progression into only G1a
      and incomplete HIV-1 reverse transcription. Costimulation through the CD28
      receptor and transition into G1b was required to efficiently complete the reverse
      transcription process. These findings have relevance to immune activation in
      vivo, since lymphocytes rendered anergic by a single activation signal would be
      nonpermissive for productive infection with HIV-1. Importantly, these data also
      suggest that HIV vector-based genetic transduction strategies might be successful
      only in target cells that transition into the G1b phase of the cell cycle.

PMID- 9525644
TI  - The proteolytic cleavage of human immunodeficiency virus type 1 Nef does not
      correlate with its ability to stimulate virion infectivity.
AB  - The Nef protein of human immunodeficiency virus type 1 (HIV-1) promotes virion
      infectivity through mechanisms that are yet ill defined. Some Nef is incorporated
      into particles, where it is cleaved by the viral protease between amino acids 57
      and 58. The functional significance of this event, which liberates the C-terminal
      core domain of the protein from its membrane-associated N terminus, is unknown.
      To address this question, we examined the modalities of Nef virion association
      and processing. We found that although significant levels of Nef were detected in
      HIV-1 virions partly in a cleaved form, cell-specific variations existed in the
      efficiency of Nef proteolytic processing. The virion association of Nef was
      strongly enhanced by myristoylation but did not require other HIV-1-specific
      proteins, since Nef was efficiently incorporated into and cleaved inside murine
      leukemia virus particles. Substituting alanine for tryptophan57 decreased the
      efficiency of Nef processing, while mutating leucine58 had little effect. In
      contrast, replacing both of these residues simultaneously almost completely
      prevented this process. However, when the resulting mutants were compared with a
      wild-type control in viral infectivity assays, no correlation was found between
      the levels of cleavage and the ability to stimulate virion infectivity.
      Furthermore, simian immunodeficiency virus Nef, which lacks the sequence
      recognized by the protease and as a consequence is not cleaved despite its
      incorporation into virions, could stimulate the infectivity of a nef-defective
      HIV-1 variant as efficiently as HIV-1 Nef. On these bases, we conclude that the
      proteolytic processing of Nef is not required for the ability of this protein to
      enhance virion infectivity.

PMID- 9525643
TI  - B-lymphocyte proliferation during bovine leukemia virus-induced persistent
      lymphocytosis is enhanced by T-lymphocyte-derived interleukin-2.
AB  - Bovine leukemia virus (BLV)-induced persistent lymphocytosis is characterized by
      a polyclonal expansion of CD5+ B lymphocytes. To examine the role of the cytokine
      microenvironment in this virus-induced B-lymphocyte expansion, the expression of
      interleukin-2 (IL-2), IL-4, IL-10, and gamma interferon (IFN-gamma) mRNA, was
      measured in stimulated peripheral blood mononuclear cells from persistently
      lymphocytotic BLV-infected cows, nonlymphocytotic BLV-infected cows, and
      uninfected cows. IL-2 and IL-10 mRNA expression and IL-2 functional activity were
      significantly increased when peripheral blood mononuclear cells from persistently
      lymphocytotic cows were stimulated with concanavalin A (ConA). Additionally,
      during persistent lymphocytosis, peak IL-2 and IL-10 mRNA expression was delayed,
      and elevated expression was prolonged. To determine the potential biologic
      importance of increased IL-2 and IL-10 expression, the response of isolated B
      lymphocytes from persistently lymphocytotic cows to human recombinant cytokines
      and to cytokine-containing supernatants from isolated T lymphocytes was examined.
      While recombinant human IL-10 (rhIL-10) did not consistently induce detectable
      changes, rhIL-2 increased viral protein (p24) and IL-2 receptor expression in
      isolated B lymphocytes from persistently lymphocytotic cows. Additionally, rhIL-2
      and supernatant from ConA-stimulated T lymphocytes enhanced B-lymphocyte
      proliferation. The stimulatory activity of the T-lymphocyte supernatant could be
      completely inhibited with a polyclonal anti-rhIL-2 antibody. Finally, polyclonal
      anti-rhIL-2 antibody, as well as anti-BLV antibody, inhibited spontaneous
      proliferation of peripheral blood mononuclear cells from persistently
      lymphocytotic cows, demonstrating that the spontaneous lymphoproliferation
      characteristic of BLV-induced persistent lymphocytosis is IL-2 dependent and
      antigen dependent. Collectively, these findings strongly suggest that increased T
      lymphocyte expression of IL-2 in BLV-infected cows contributes to development
      and/or maintenance of persistent B lymphocytosis.

PMID- 9525645
TI  - The bovine leukemia virus encapsidation signal is composed of RNA secondary
      structures.
AB  - The encapsidation signal of bovine leukemia virus (BLV) was previously shown by
      deletion analysis to be discontinuous and to extend into the 5' end of the gag
      gene (L. Mansky et al., J. Virol. 69:3282-3289, 1995). The global minimum-energy
      optimal folding for the entire BLV RNA, including the previously mapped primary
      and secondary encapsidation signal regions, was analyzed. Two stable stem-loop
      structures (located just downstream of the gag start codon) were predicted within
      the primary signal region, and one stable stem-loop structure (in the gag gene)
      was predicted in the secondary signal region. Based on these predicted
      structures, we introduced a series of mutations into the primary and secondary
      encapsidation signals in order to explore the sequence and structural information
      contained within these regions. The replication efficiency and levels of
      cytoplasmic and virion RNA were analyzed for these mutants. Mutations that
      disrupted either or both of the predicted stem-loop structures of the primary
      signal reduced the replication efficiency by factors of 7 and 40, respectively;
      similar reductions in RNA encapsidation efficiency were observed. The mutant with
      both stem-loop structures disrupted had a phenotype similar to that of a mutant
      containing a deletion of the entire primary signal region. Mutations that
      disrupted the predicted stem-loop structure of the secondary signal led to
      similar reductions (factors of 4 to 6) in both the replication and RNA
      encapsidation efficiencies. The introduction of compensatory mutations into
      mutants from both the primary and secondary signal regions, which restored the
      predicted stem-loop structures, led to levels of replication and RNA
      encapsidation comparable to those of virus containing the wild-type encapsidation
      signal. Replacement of the BLV RNA region containing the primary and secondary
      encapsidation signals with a similar region from human T-cell leukemia virus
      (HTLV) type 1 or type 2 led to virus replication at three-quarters or one-fifth
      of the level of the parental virus, respectively. The results from both the
      compensatory mutants and BLV-HTLV chimeras indicate that the encapsidation
      sequences are recognized largely by their secondary or tertiary structures.

PMID- 9525646
TI  - Infection of human B lymphocytes with lymphocryptoviruses related to Epstein-Barr
      virus.
AB  - Lymphocryptoviruses (LCVs) naturally infecting Old World nonhuman primates are
      closely related to the human LCV, Epstein-Barr virus (EBV), and share similar
      genome organization and sequences, biologic properties, epidemiology, and
      pathogenesis. LCVs can efficiently immortalize B lymphocytes from the autologous
      species, but the ability of a given LCV to immortalize B cells from other Old
      World primate species is variable. We found that LCV from rhesus monkeys did not
      immortalize human B cells, and EBV did not immortalize rhesus monkey B cells. In
      this study, baboon LCV could not immortalize human peripheral blood B cells but
      could readily immortalize rhesus monkey B cells. Thus, efficient LCV-induced B
      cell immortalization across distant Old World primate species appears to be
      restricted by a species-specific block. To further characterize this species
      restriction, we first cloned the rhesus monkey LCV major membrane glycoprotein
      and discovered that the binding epitope for the EBV receptor, CD21, was highly
      conserved. Stable infections of human B cells with recombinant amplicons packaged
      in rhesus monkey or baboon LCV envelopes were also consistent with a species
      restricted block occurring after virus binding and penetration. Transient
      infections of human B cells with simian LCV resulted in latent LCV EBNA-2 gene
      expression and activation of cell CD23 gene expression. EBV-immortalized human B
      cells could be coinfected with baboon LCV, and the simian virus persisted and
      replicated in human B cells. Thus, several lines of evidence indicate that the
      species restriction for efficient LCV-induced B-cell immortalization occurs
      beyond virus binding and penetration. This has important implications for the
      study of LCV infection in Old World primate models and for human
      xenotransplantation where simian LCVs may be inadvertently introduced into
      humans.

PMID- 9525647
TI  - Functional analysis of the CAAT box in the major late promoter of the subgroup C
      human adenoviruses.
AB  - Comparisons among sequences predicted to encode the major late promoter (MLP) of
      adenoviruses from a wide variety of host species show that an inverted CAAT box
      is among the most highly conserved transcription elements found in the putative
      MLPs. The high degree of conservation suggests that the CAAT box plays an
      important role in the function of the MLP in vivo, an idea supported by a
      previous mutational analysis of the core CCAAT sequence. To address the
      importance of the CAAT box, in terms both of quantitative levels of transcription
      and of specificity, a further set of mutations was created and examined in the
      context of the viral genome. One mutation, CAAT5, contains individual changes at
      five positions, four of which correspond to invariant residues in a CAAT box
      consensus derived either by computer analysis or empirically. The CAAT5 mutation
      had no discernible phenotype by itself but when coupled with the previously
      described USF0 mutation, which disrupts binding of the upstream stimulating
      factor (USF) but is otherwise phenotypically silent, gave rise to virus with a
      severe replication deficiency. Nuclear run-on assays showed that transcription
      initiation at the mutant MLP was significantly reduced compared with that of the
      wild type or the virus containing CAAT5 alone. Replication of the double mutant
      was lower than that of the previously described USF0::CCCAT virus, suggesting
      that the additional mutations in the CAAT box had further lowered the binding of
      transcription factor CP1 (also called CBF, NF-Y). Replacement of the CAAT box by
      an ATF binding site or an OCT1 binding site had no phenotypic effect in an
      otherwise wild-type background, but replacement in a USF0::CCCAT background led
      to only partial restoration of the wild-type phenotype. The failure to restore
      the functional redundancy normally exhibited by the CAAT box and the proximal
      upstream activating element is consistent with the idea that in the adenovirus
      MLP the CAAT box is preferred over others as the distal transcriptional element.

PMID- 9525648
TI  - Evidence of a role for phosphatidylinositol 3-kinase activation in the blocking
      of apoptosis by polyomavirus middle T antigen.
AB  - A polyomavirus mutant (315YF) blocked in binding phosphatidylinositol 3-kinase
      (PI 3-kinase) has previously been shown to be partially deficient in
      transformation and to induce fewer tumors and with a significant delay compared
      to wild-type virus. The role of polyomavirus middle T antigen-activated PI 3
      kinase in apoptosis was investigated as a possible cause of this behavior. When
      grown in medium containing 1D-3-deoxy-3-fluoro-myo-inositol to block formation of
      3'-phosphorylated phosphatidylinositols, F111 rat fibroblasts transformed by wild
      type polyomavirus (PyF), but not normal F111 cells, showed a marked loss of
      viability with evidence of apoptosis. Similarly, treatment with wortmannin, an
      inhibitor of PI 3-kinase, stimulated apoptosis in PyF cells but not in normal
      cells. Activation of Akt, a serine/threonine kinase whose activity has been
      correlated with regulation of apoptosis, was roughly twofold higher in F111 cells
      transformed by either wild-type virus or mutant 250YS blocked in binding Shc
      compared to cells transformed by mutant 315YF. In the same cells, levels of
      apoptosis were inversely correlated with Akt activity. Apoptosis induced by serum
      withdrawal in Rat-1 cells expressing a temperature-sensitive p53 was shown to be
      at least partially p53 independent. Expression of either wild-type or 250YS
      middle T antigen inhibited apoptosis in serum-starved Rat-1 cells at both
      permissive and restrictive temperatures for p53. Mutant 315YF middle T antigen
      was partially defective for inhibition of apoptosis in these cells. The results
      indicate that unlike other DNA tumor viruses which block apoptosis by
      inactivation of p53, polyomavirus achieves protection from apoptotic death
      through a middle T antigen-PI 3-kinase-Akt pathway that is at least partially p53
      independent.

PMID- 9525649
TI  - Viral coat protein peptides with limited sequence homology bind similar domains
      of alfalfa mosaic virus and tobacco streak virus RNAs.
AB  - An unusual and distinguishing feature of alfalfa mosaic virus (AMV) and
      ilarviruses such as tobacco streak virus (TSV) is that the viral coat protein is
      required to activate the early stages of viral RNA replication, a phenomenon
      known as genome activation. AMV-TSV coat protein homology is limited; however,
      they are functionally interchangeable in activating virus replication. For
      example, TSV coat protein will activate AMV RNA replication and vice versa.
      Although AMV and TSV coat proteins have little obvious amino acid homology, we
      recently reported that they share an N-terminal RNA binding consensus sequence
      (Ansel-McKinney et al., EMBO J. 15:5077-5084, 1996). Here, we biochemically
      compare the binding of chemically synthesized peptides that include the consensus
      RNA binding sequence and lysine-rich (AMV) or arginine-rich (TSV) environment to
      3'-terminal TSV and AMV RNA fragments. The arginine-rich TSV coat protein peptide
      binds viral RNA with lower affinity than the lysine-rich AMV coat protein
      peptides; however, the ribose moieties protected from hydroxyl radical attack by
      the two different peptides are localized in the same area of the predicted RNA
      structures. When included in an infectious inoculum, both AMV and TSV 3'-terminal
      RNA fragments inhibited AMV RNA replication, while variant RNAs unable to bind
      coat protein did not affect replication significantly. The data suggest that RNA
      binding and genome activation functions may reside in the consensus RNA binding
      sequence that is apparently unique to AMV and ilarvirus coat proteins.

PMID- 9525650
TI  - Synergistic neutralization of simian-human immunodeficiency virus SHIV-vpu+ by
      triple and quadruple combinations of human monoclonal antibodies and high-titer
      anti-human immunodeficiency virus type 1 immunoglobulins.
AB  - We have tested triple and quadruple combinations of human monoclonal antibodies
      (MAbs), which are directed against various epitopes on human immunodeficiency
      virus type 1 (HIV-1) envelope glycoproteins, and a high-titer anti-HIV-1 human
      immunoglobulin (HIVIG) preparation for their abilities to neutralize a chimeric
      simian-human immunodeficiency virus (SHIV-vpu+). This virus encodes the HIV-1
      strain IIIB env, tat, rev, and vpu genes. The quantitative nature of the Chou
      Talalay method (Adv. Enzyme Regul. 22:27-55, 1984) allows ranking of various
      combinations under identical experimental conditions. Of all triple combinations
      tested, the most potent neutralization was seen with MAbs 694/98D plus 2F5 plus
      2G12 (directed against domains on V3, gp41, and gp120, respectively) as measured
      by the total MAb concentration required to reach 90% neutralization (90%
      effective concentration [EC90], 2.0 microg/ml). All triple combinations involving
      MAbs and/or HIVIG that were tested yielded synergy with combination index values
      of < 1; the dose reduction indices (DRIs) ranged from 3.1 to 26.2 at 90%
      neutralization. When four MAbs (the previous three plus MAb F105, directed
      against the CD4 binding site) were combined, higher neutralization potency (EC90
      1.8 microg/ml) and a higher degree of synergy compared to any triple combination
      were seen. The mean DRIs of the quadruple combination were approximately twice
      that of the most synergistic triple combination. We conclude that human MAbs
      targeting different HIV-1 envelope glycoprotein epitopes exhibit strong synergy
      when used in combination, a fact that could be exploited clinically for passive
      immunoprophylaxis against HIV-1.

PMID- 9525653
TI  - Mutational analysis of the candidate internal fusion peptide of the avian
      leukosis and sarcoma virus subgroup A envelope glycoprotein.
AB  - The transmembrane subunit (TM) of the avian leukosis and sarcoma virus (ALSV)
      envelope glycoprotein (Env) contains a stretch of conserved hydrophobic amino
      acids internal to its amino terminus (residues 21 to 42). By analogy with similar
      sequences in other viral envelope glycoproteins, this region has been proposed to
      be a fusion peptide. We investigated the role of this region by changing each of
      three hydrophobic residues (Ile-21, Val-30, and Ile-39) to glutamatic acid and
      lysine in the ALSV subgroup A Env. Like wild-type (wt) Env, all six mutant Env
      proteins were proteolytically processed, oligomerized, and expressed at the cell
      surface in a form that bound Tva, the ALSV subgroup A receptor. Like wt Env,
      Ile21Glu, Ile21Lys, Va30Glu, and Val30Lys changed conformation upon binding Tva,
      as assayed by sensitivity to thermolysin. Ile39Glu and Ile39Lys were cleaved by
      thermolysin in both the absence and presence of Tva. Although incorporated into
      virus particles at approximately equal levels, all mutant Envs were compromised
      in their ability to support infection. The mutants at residues 21 and 30 showed
      levels of infection 2 to 3 orders of magnitude lower than that of wt Env. The
      mutants at residue 39 were noninfectious. Furthermore, none of the mutants
      displayed activity in a cell-cell fusion assay. Our results support the
      contention that residues 21 to 42 of ALSV subgroup A Env constitute its fusion
      peptide.

PMID- 9525651
TI  - In vitro packaging of adeno-associated virus DNA.
AB  - We have developed an in vitro procedure for packaging of recombinant adeno
      associated virus (AAV). By using AAV replicative-form DNA as the substrate, it is
      possible to synthesize an infectious AAV particle in vitro that can be used to
      transfer a marker gene to mammalian cells. The packaging procedure requires the
      presence of both the AAV Rep and capsid proteins. Two kinds of in vitro products
      can be formed which facilitate DNA transfer. Both are resistant to heat and have
      a density in cesium chloride gradients that is indistinguishable from that of the
      in vivo-synthesized wild-type virus. This indicates that the particles formed
      have the appropriate protein-to-DNA ratio and a structure that shares the heat
      resistance of mature AAV particles. The two types of particles can be
      distinguished by their sensitivity to chloroform and DNase I treatment. The
      chloroform-resistant product is, by several criteria, an authentic AAV particle.
      In addition to having the correct density and being resistant to treatment with
      chloroform, DNase I, and heat, this particle is efficiently synthesized only if
      the AAV genome contains intact terminal repeats, which are known to be required
      for AAV packaging. It is also precipitated by a monoclonal antibody that
      recognizes mature virus particles but not bound by an antibody that recognizes
      monomeric or denatured capsid proteins. The chloroform-resistant species is not
      made when aphidicolin is present in the reaction mixture, suggesting that active
      DNA replication is required for in vitro packaging. In contrast, the chloroform
      sensitive product has several features that suggest it is an incompletely
      assembled virus particle. It is sensitive to DNase I, does not require the
      presence of AAV terminal repeats, and is capable of transferring DNA that is
      theoretically too large to package. Sucrose gradient centrifugation of the in
      vitro-synthesized products reveals that the particles have sedimentation values
      between 60S and 110S, which is consistent with partially assembled and mature AAV
      particles. The in vitro packaging procedure should be useful for studying the
      mechanism by which a human icosahedral DNA virus particle is assembled, and it
      may be useful for producing recombinant AAV for gene therapy. The chloroform
      sensitive particle may also be useful for transferring DNA that is too large to
      be packaged in mature recombinant AAV.

PMID- 9525652
TI  - In vivo replication capacity rather than in vitro macrophage tropism predicts
      efficiency of vaginal transmission of simian immunodeficiency virus or
      simian/human immunodeficiency virus in rhesus macaques.
AB  - We used the rhesus macaque model of heterosexual human immunodeficiency virus
      (HIV) transmission to test the hypothesis that in vitro measures of macrophage
      tropism predict the ability of a primate lentivirus to initiate a systemic
      infection after intravaginal inoculation. A single atraumatic intravaginal
      inoculation with a T-cell-tropic molecular clone of simian immunodeficiency virus
      (SIV), SIVmac239, or a dualtropic recombinant molecular clone of SIV,
      SIVmac239/1A11/239, or uncloned dualtropic SIVmac251 or uncloned dualtropic
      simian/human immunodeficiency virus (SHIV) 89.6-PD produced systemic infection in
      all rhesus macaques tested. However, vaginal inoculation with a dualtropic
      molecular clone of SIV, SIVmac1A11, resulted in transient viremia in one of two
      rhesus macaques. It has previously been shown that 12 intravaginal inoculations
      with SIVmac1A11 resulted in infection of one of five rhesus macaques (M. L.
      Marthas, C. J. Miller, S. Sutjipto, J. Higgins, J. Torten, B. L. Lohman, R. E.
      Unger, H. Kiyono, J. R. McGhee, P. A. Marx, and N. C. Pedersen, J. Med. Primatol.
      21:99-107, 1992). In addition, SHIV HXBc2, which replicates in monkey
      macrophages, does not infect rhesus macaques following multiple vaginal
      inoculations, while T-cell-tropic SHIV 89.6 does (Y. Lu, P. B. Brosio, M.
      Lafaile, J. Li, R. G. Collman, J. Sodroski, and C. J. Miller, J. Virol. 70:3045
      3050, 1996). These results demonstrate that in vitro measures of macrophage
      tropism do not predict if a SIV or SHIV will produce systemic infection after
      intravaginal inoculation of rhesus macaques. However, we did find that the level
      to which these viruses replicate in vivo after intravenous inoculation predicts
      the outcome of intravaginal inoculation with each virus.

PMID- 9525654
TI  - The receptor binding site of feline leukemia virus surface glycoprotein is
      distinct from the site involved in virus neutralization.
AB  - The external surface glycoprotein (SU) of feline leukemia virus (FeLV) contains
      sites which define the viral subgroup and induce virus-neutralizing antibodies.
      The subgroup phenotypic determinants have been located to a small variable
      region, VR1, towards the amino terminus of SU. The sites which function as
      neutralizing epitopes in vivo are unknown. Recombinant SU proteins were produced
      by using baculoviruses that contained sequences encoding the SUs of FeLV subgroup
      A (FeLV-A), FeLV-C, and two chimeric FeLVs (FeLV-215 and FeLV-VC) in which the
      VR1 domain of FeLV-A had been replaced by the corresponding regions of FeLV-C
      isolates. The recombinant glycoproteins, designated Bgp70-A, -C, -215, and -VC,
      respectively, were similar to their wild-type counterparts in several immunoblots
      and inhibited infection of susceptible cell lines in a subgroup-specific manner.
      Thus, Bgp70-A interfered with infection by FeLV-A, whereas Bgp70-C, -VC, and -215
      did not. Conversely, Bgp70-C, -VC, and -215 blocked infection with FeLV-C, while
      Bgp70-A had no effect. These results indicate that the site on SU which binds to
      the FeLV cell surface receptor was preserved in the recombinant glycoproteins. It
      was also found that the recombinant proteins were able to bind naturally
      occurring neutralizing antibodies. Bgp70-A, -VC, and -215 interfered with the
      action of anti-FeLV-A neutralizing antibodies, whereas Bgp70-C did not.
      Furthermore, Bgp70-C interfered with the action of anti-FeLV-C neutralizing
      antibodies, while the other proteins did not. These results indicate that the
      neutralizing epitope(s) of FeLV SU lies outside the subgroup-determining VR1
      domain.

PMID- 9525655
TI  - Intracellular complexes of viral spike and cellular receptor accumulate during
      cytopathic murine coronavirus infections.
AB  - Murine hepatitis virus (MHV) infections exhibit remarkable variability in
      cytopathology, ranging from acutely cytolytic to essentially asymptomatic levels.
      In this report, we assess the role of the MHV receptor (MHVR) in controlling this
      variable virus-induced cytopathology. We developed human (HeLa) cell lines in
      which the MHVR was produced in a regulated fashion by placing MHVR cDNA under the
      control of an inducible promoter. Depending on the extent of induction, MHVR
      levels ranged from less than approximately 1,500 molecules per cell (designated
      R(lo)) to approximately 300,000 molecules per cell (designated R(hi)). Throughout
      this range, the otherwise MHV-resistant HeLa cells were rendered susceptible to
      infection. However, infection in the R(lo) cells occurred without any overt
      evidence of cytopathology, while the corresponding R(hi) cells died within 14 h
      after infection. When the HeLa-MHVR cells were infected with vaccinia virus
      recombinants encoding MHV spike (S) proteins, the R(hi) cells succumbed within 12
      h postinfection; R(lo) cells infected in parallel were intact, as judged by
      trypan blue exclusion. This acute cytopathology was not due solely to syncytium
      formation between the cells producing S and MHVR, because fusion-blocking
      antiviral antibodies did not prevent it. These findings raised the possibility of
      an intracellular interaction between S and MHVR in the acute cell death. Indeed,
      we identified intracellular complexes of S and MHVR via coimmunoprecipitation of
      endoglycosidase H-sensitive forms of the two proteins. We suggest that MHV
      infections can become acutely cytopathic once these intracellular complexes rise
      above a critical threshold level.

PMID- 9525656
TI  - Rat parvovirus type 1: the prototype for a new rodent parvovirus serogroup.
AB  - A newly recognized parvovirus of laboratory rats, designated rat parvovirus type
      1a (RPV-1a), was found to be antigenically distinct. It was cloned, sequenced,
      and compared with the University of Massachusetts strain of rat virus (RV-UMass)
      and other autonomous parvoviruses. RPV-1a VP1 identity with these viruses never
      exceeded 69%, thus explaining its antigenic divergence. In addition, RPV-1a had
      reduced amino acid identity in NS coding regions (82%), reflecting phylogenetic
      divergence from other rodent parvoviruses. RPV-1a infection in rats had a
      predilection for endothelium and lymphoid tissues as previously reported for RV.
      Infectious RPV-1a was isolated 3 weeks after inoculation of infant rats,
      suggesting that it, like RV, may result in persistent infection. In contrast to
      RV, RPV-1a was enterotropic, a characteristic previously associated with
      parvovirus infections of mice rather than rats. RPV-1a also differed from RV in
      that infection was nonpathogenic for infant rats under conditions where RV
      infection causes high morbidity and mortality. Thus, RPV-1a is the prototype
      virus of an antigenically, genetically, and biologically distinct rodent
      parvovirus serogroup.

PMID- 9525657
TI  - Loss of viral fitness associated with multiple Gag and Gag-Pol processing defects
      in human immunodeficiency virus type 1 variants selected for resistance to
      protease inhibitors in vivo.
AB  - We examined the viral replicative capacity and protease-mediated processing of
      Gag and Gag-Pol precursors of human immunodeficiency virus (HIV) variants
      selected for resistance to protease inhibitors. We compared recombinant viruses
      carrying plasma HIV RNA protease sequences obtained from five patients before
      protease inhibitor therapy and after virus escape from the treatment. Paired
      pretherapy-postresistance reconstructed viruses were evaluated for HIV
      infectivity in a quantitative single-cycle titration assay and in a lymphoid cell
      propagation assay. We found that all reconstructed resistant viruses had a
      reproducible decrease in their replicative capacity relative to their parental
      pretherapy counterparts. The extent of this loss of infectivity was pronounced
      for some viruses and more limited for others, irrespective of the inhibitor used
      and of the level of resistance. In resistant viruses, the efficiency of Gag and
      Gag-Pol precursor cleavage by the protease was impaired to different extents, as
      shown by the accumulation of several cleavage intermediates in purified particle
      preparations. We conclude that protease inhibitor-resistant HIV variants selected
      during therapy have an impaired replicative capacity related to multiple defects
      in the processing of Gag and Gag-Pol polyprotein precursors by the protease.

PMID- 9525658
TI  - Persistence and expression of the herpes simplex virus genome in the absence of
      immediate-early proteins.
AB  - The immediate-early (IE) proteins of herpes simplex virus (HSV) function on input
      genomes and affect many aspects of host cell metabolism to ensure the efficient
      expression and regulation of the remainder of the genome and, subsequently, the
      production of progeny virions. Due to the many and varied effects of IE proteins
      on host cell metabolism, their expression is not conducive to normal cell
      function and viability. This presents a major impediment to the use of HSV as a
      vector system. In this study, we describe a series of ICP4 mutants that are
      defective in different subsets of the remaining IE genes. One mutant, d109, does
      not express any of the IE proteins and carries a green fluorescent protein (GFP)
      transgene under the control of the human cytomegalovirus IE promoter (HCMVIEp).
      d109 was nontoxic to Vero and human embryonic lung (HEL) cells at all
      multiplicities of infection tested and was capable of establishing persistent
      infections in both of these cell types. Paradoxically, the genetic manipulations
      that were required to eliminate toxicity and allow the genome to persist in cells
      for long periods of time also dramatically lowered the level of transgene
      expression. Efficient expression of the HCMVIEp-GFP transgene in the absence of
      ICP4 was dependent on the ICP0 protein. In d109-infected cells, the level of
      transgene expression was very low in most cells but abundant in a small
      subpopulation of cells. However, expression of the transgene could be induced in
      cells containing quiescent d109 genomes weeks after the initial infection,
      demonstrating the functionality of the persisting genomes.

PMID- 9525659
TI  - Localization of human cytomegalovirus structural proteins to the nuclear matrix
      of infected human fibroblasts.
AB  - The intranuclear assembly of herpesvirus subviral particles remains an
      incompletely understood process. Previous studies have described the nuclear
      localization of capsid and tegument proteins as well as intranuclear
      tegumentation of capsid-like particles. The temporally and spatially regulated
      replication of viral DNA suggests that assembly may also be regulated by
      compartmentalization of structural proteins. We have investigated the
      intranuclear location of several structural and nonstructural proteins of human
      cytomegalovirus (HCMV). Tegument components including pp65 (ppUL83) and ppUL69
      and capsid components including the major capsid protein (pUL86) and the small
      capsid protein (pUL48/49) were retained within the nuclear matrix (NM), whereas
      the immediate-early regulatory proteins IE-1 and IE-2 were present in the soluble
      nuclear fraction. The association of pp65 with the NM resisted washes with 1 M
      guanidine hydrochloride, and direct binding to the NM could be demonstrated by
      far-Western blotting. Furthermore, pp65 exhibited accumulation along the nuclear
      periphery and in far-Western analysis bound to proteins which comigrated with
      proteins of the size of nuclear lamins. A direct interaction between pp65 and
      lamins was demonstrated by coprecipitation of lamins in immune complexes
      containing pp65. Together, our findings provide evidence that major virion
      structural proteins localized to a nuclear compartment, the NM, during permissive
      infection of human fibroblasts.

PMID- 9525660
TI  - Herpes simplex virus gD and virions accumulate in endosomes by mannose 6
      phosphate-dependent and -independent mechanisms.
AB  - Herpes simplex virus (HSV) glycoprotein D (gD) is modified with mannose 6
      phosphate (M6P) and binds to M6P receptors (MPRs). MPRs are involved in the well
      characterized pathway by which lysosomal enzymes are directed to lysosomes via a
      network of endosomal membranes. Based on the impaired ability of HSV to form
      plaques under conditions in which glycoproteins could not interact with MPRs, we
      proposed that MPRs may function during HSV egress or cell-to-cell spread (C. R.
      Brunetti, R. L. Burke, B. Hoflack, T. Ludwig, K. S. Dingwell, and D. C. Johnson,
      J. Virol. 69:3517-3528, 1995). To further analyze M6P modification and
      intracellular trafficking of gD in the absence of other HSV proteins, adenovirus
      (Ad) vectors were used to express soluble and membrane-anchored forms of gD. Both
      membrane-bound and soluble gD were modified with M6P residues and were localized
      to endosomes that contained the 275-kDa MPR or the transferrin receptor. Similar
      results were observed in HSV-infected cells. Cell fractionation experiments
      showed that gD was not present in lysosomes. However, a mutant form of gD and
      another HSV glycoprotein, gI, that were not modified with M6P were also found in
      endosomes in HSV-infected cells. Moreover, a substantial fraction of the HSV
      nucleocapsid protein VP6 was found in endosomes, consistent with accumulation of
      virions in an endosomal compartment. Therefore, it appears that HSV glycoproteins
      and virions are directed to endosomes, by M6P-dependent as well as by M6P
      independent mechanisms, either as part of the virus egress pathway or by
      endocytosis from the cell surface.

PMID- 9525661
TI  - Human immunodeficiency virus neurotropism: an analysis of viral replication and
      cytopathicity for divergent strains in monocytes and microglia.
AB  - Productive replication of human immunodeficiency virus type 1 (HIV-1) in brain
      macrophages and microglia is a critical component of viral neuropathogenesis.
      However, how virus-macrophage interactions lead to neurological disease remains
      incompletely understood. Possibly, a differential ability of virus to replicate
      in brain tissue macrophages versus macrophages in other tissues underlies HIV-1
      neurovirulence. To these ends, we established systems for the isolation and
      propagation of pure populations of human microglia and then analyzed the viral
      life cycles of divergent HIV-1 strains in these cells and in cultured monocytes
      by using identical viral inocula and indicator systems. The HIV-1 isolates
      included those isolated from blood, lung tissue, cerebrospinal fluids (CSF), and
      brain tissues of infected subjects: HIV-1(ADA) and HIV-1(89.6) (from peripheral
      blood mononuclear cells), HIV-1(DJV) and HIV-1(JR-FL) (from brain tissue), HIV
      1(SF162) (from CSF), and HIV-1(BAL) (from lung tissue). The synthesis of viral
      nucleic acids and viral mRNA, cytopathicity, and release of progeny virions were
      assessed. A significant heterogeneity among macrophage-tropic isolates for
      infection of monocytes and microglia was demonstrated. Importantly, a complete
      analysis of the viral life cycle revealed no preferential differences in the
      abilities of the HIV-1 strains tested to replicate in microglia and/or monocytes.
      Macrophage tropism likely dictates the abilities of HIV-1 to invade, replicate,
      and incite disease within its microglial target cells.

PMID- 9525663
TI  - Membrane organization of bluetongue virus nonstructural glycoprotein NS3.
AB  - The smallest RNA segment (S10) of bluetongue virus (an orbivirus, family
      Reoviridae) encodes two closely related nonstructural proteins, the 229-amino
      acid (aa) NS3 and the 216-aa NS3A. The proteins are found in glycosylated and
      nonglycosylated forms in infected cells (X. Wu, H. Iwata, S.-Y. Chen, R. W.
      Compans and P. Roy J. Virol. 66:7104-7112, 1992). The NS3/NS3A proteins have two
      hydrophobic domains (aa 118 to 141 and 162 to 182) and two potential asparagine
      linked glycosylation sites (aa 63 and 150), one of which is located between the
      hydrophobic domains. To determine whether these features were used in the mature
      protein forms, we generated a series of mutants of the S10 gene and expressed
      them by using the vaccinia virus T7 polymerase transient-expression system. Our
      data indicate that both hydrophobic domains of NS3 span the cell membrane and
      that only the site at aa 150 is responsible for N-linked glycosylation of the NS3
      proteins.

PMID- 9525662
TI  - Role of the beta-chemokine receptors CCR3 and CCR5 in human immunodeficiency
      virus type 1 infection of monocytes and microglia.
AB  - Human immunodeficiency virus type 1 (HIV-1) infection in mononuclear phagocyte
      lineage cells (monocytes, macrophages, and microglia) is a critical component in
      the pathogenesis of viral infection. Viral replication in macrophages serves as a
      reservoir, a site of dissemination, and an instigator for neurological sequelae
      during HIV-1 disease. Recent studies demonstrated that chemokine receptors are
      necessary coreceptors for HIV-1 entry which determine viral tropism for different
      cell types. To investigate the relative contribution of the beta-chemokine
      receptors CCR3 and CCR5 to viral infection of mononuclear phagocytes we utilized
      a panel of macrophage-tropic HIV-1 strains (from blood and brain tissue) to
      infect highly purified populations of monocytes and microglia. Antibodies to CD4
      (OKT4A) abrogated HIV-1 infection. The beta chemokines and antibodies to CCR3
      failed to affect viral infection of both macrophage cell types. Antibodies to
      CCR5 (3A9) prevented monocyte infection but only slowed HIV replication in
      microglia. Thus, CCR5, not CCR3, is an essential receptor for HIV-1 infection of
      monocytes. Microglia express both CCR5 and CCR3, but antibodies to them fail to
      inhibit viral entry, suggesting the presence of other chemokine receptors for
      infection of these cells. These studies demonstrate the importance of mononuclear
      phagocyte heterogeneity in establishing HIV-1 infection and persistence.

PMID- 9525665
TI  - Studies of the nucleopolyhedrovirus infection process in insects by using the
      green fluorescence protein as a reporter.
AB  - A recombinant Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV)
      expressing the green fluorescence protein (GFP) under the control of the AcMNPV
      polyhedrin promoter was constructed to study the spatial and temporal regulation
      of baculovirus infection in a permissive host. Larvae that ingested AcMNPV-GFP
      showed localized expression of GFP in the midgut epithelial cells, as well as
      hemocytes, at 24 h postinfection. The presence of fluorescence in these tissues
      indicated not only that the virus was replicating but also that the very late
      viral proteins were being synthesized. Secondary infection occurred within the
      tracheal cells throughout the body cavity, confirming earlier reports, and these
      foci of infection allowed entry of the virus into other tissues, such as the
      epidermis and the fat body.

PMID- 9525664
TI  - A cytopathogenic, apoptosis-inducing variant of hepatitis A virus.
AB  - A cytopathogenic variant of hepatitis A virus (HAV(cyt/HB1.1)) was isolated from
      persistently infected BS-C-1 cells by serial passages in FRhK-4 cells. This virus
      shows a rapid replication pattern and high final titers are obtained, which are
      main characteristics of cytopathogenic HAVs. Sequencing of the nontranslated
      regions and the coding regions for 2ABC and 3AB revealed that mutations are
      distributed all over these regions and that certain mutated sites correspond to
      those in other cytopathogenic HAV variants. Investigating the mechanisms causing
      the cytopathic effect in FRhK-4 cells infected with this variant, we found that
      an apoptotic reaction takes place.

PMID- 9525666
TI  - Efficient expression and rapid purification of human T-cell leukemia virus type 1
      protease.
AB  - Human T-cell leukemia virus type 1 (HTLV-1) is an oncovirus that is clinically
      associated with adult T-cell leukemia. We report here the construction of a pET19
      based expression clone containing HTLV-1 protease fused to a decahistidine
      containing leader peptide. The recombinant protein is efficiently expressed in
      Escherichia coli, and the fusion protein can be easily purified by affinity
      chromatography. Active mature protease in yields in excess of 3 mg/liter of
      culture can then be obtained by a novel two-step refolding and autoprocessing
      procedure. The purified enzyme exhibited Km and Kcat, values of 0.3 mM and 0.143
      sec(-1) at pH 5.3 and was inhibited by pepstatin A.

PMID- 9525667
TI  - Enhancement of aquareovirus infectivity by treatment with proteases: mechanism of
      action.
AB  - The effects of protease digestion on the polypeptide composition and on the
      infectivity of striped bass virus, an aquareovirus, were examined. Both trypsin
      and chymotrypsin enhanced the infectivity of the virus. Enhancement of
      infectivity was correlated with the digestion of the outer capsid protein, VP7.
      These studies support the assertion that VP7 is the outermost capsid protein and
      suggest that VP4 and VP5 are exposed on the outer surface of infectious
      particles. The possible role of VP7 in the variation in virulence observed among
      aquareovirus isolates is discussed.

PMID- 9525668
TI  - Rotavirus 2/6 viruslike particles administered intranasally with cholera toxin,
      Escherichia coli heat-labile toxin (LT), and LT-R192G induce protection from
      rotavirus challenge.
AB  - We have shown that rotavirus 2/6 viruslike particles composed of proteins VP2 and
      VP6 (2/6-VLPs) administered to mice intranasally with cholera toxin (CT) induced
      protection from rotavirus challenge, as measured by virus shedding. Since it is
      unclear if CT will be approved for human use, we evaluated the adjuvanticity of
      Escherichia coli heat-labile toxin (LT) and LT-R192G. Mice were inoculated
      intranasally with 10 microg of 2/6-VLPs combined with CT, LT, or LT-R192G. All
      three adjuvants induced equivalent geometric mean titers of rotavirus-specific
      serum antibody and intestinal immunoglobulin G (IgG). Mice inoculated with 2/6
      VLPs with LT produced significantly higher titers of intestinal IgA than mice
      given CT as the adjuvant. All mice inoculated with 2/6-VLPs mixed with LT and LT
      R192G were totally protected (100%) from rotavirus challenge, while mice
      inoculated with 2/6-VLPs mixed with CT showed a mean 91% protection from
      challenge. The availability of a safe, effective mucosal adjuvant such as LT
      R192G will increase the practicality of administering recombinant vaccines
      mucosally.

PMID- 9525669
TI  - Differentiation of promonocytic U937 subclones into macrophagelike phenotypes
      regulates a cellular factor(s) which modulates fusion/entry of macrophagetropic
      human immunodeficiency virus type 1.
AB  - Monocytes/macrophages (M/M) and CD4+ T cells are two important targets of human
      immunodeficiency virus (HIV) infection. Different strains of HIV-1 vary markedly
      in their abilities to infect cells belonging to the M/M lineage. Macrophagetropic
      (M-tropic) HIV-1 strains replicate well in primary lymphocytes as well as in
      primary macrophages; however, they generally infect T-cell lines poorly, if at
      all. Although promonocytic cell lines such as U937 have been used as in vitro
      models of HIV-1 infection of M/M, these cell lines are susceptible to certain T
      cell-tropic (T-tropic) HIV-1 strains but are resistant to M-tropic HIV-1. In this
      study, we demonstrate that (i) certain U937 clones ("plus" clones), which are
      susceptible only to T-tropic HIV-1, become highly susceptible to M-tropic HIV-1
      upon differentiation with retinoic acid (RA); (ii) other U937 clones ("minus"
      clones), which are resistant to both T- and M-tropic HIV-1, remain resistant to
      both viruses; and (iii) RA treatment induces expression of CCR5, a fusion/entry
      cofactor for M-tropic HIV-1 in both types of U937 clones, and yet enhances the
      fusogenicity of the plus clones, but not the minus clones, with M-tropic Env's.
      These results indicate that the major restriction of M-tropic HIV-1 infection in
      promonocytic cells occurs at the fusion/entry level, that differentiation into
      macrophage-like phenotypes renders some of these cells highly susceptible to
      infection with M-tropic HIV-1, and that CD4 and CCR5 may not be the only
      determinants of fusion/entry of M-tropic HIV-1 in these cells.

PMID- 9525670
TI  - Molluscum contagiosum virus topoisomerase: purification, activities, and response
      to inhibitors.
AB  - Molluscum contagiosum virus (MCV), the only member of the Molluscipoxvirus genus,
      causes benign papules in healthy people but disfiguring lesions in
      immunocompromised patients. The sequence of MCV has been completed, revealing
      that MCV encodes a probable type I topoisomerase enzyme. All poxviruses sequenced
      to date also encode type I topoisomerases, and in the case of vaccinia virus the
      topoisomerase has been shown to be essential for replication. Thus, inhibitors of
      the MCV topoisomerase might be useful as antiviral agents. We have cloned the
      gene for MCV topoisomerase, overexpressed and purified the protein, and begun to
      characterize its activities in vitro. Like other eukaryotic type I
      topoisomerases, MCV topoisomerase can relax both positive and negative
      supercoils. An analysis of the cleavage of plasmid and oligonucleotide substrates
      indicates that cleavage by MCV topoisomerase is favored just 3' of the sequence
      5' (T/C)CCTT 3', resulting in formation of a covalent bond to the 3' T residue,
      as with other poxvirus topoisomerases. We identified solution conditions
      favorable for activity and measured the rate of formation and decay of the
      covalent intermediate. MCV topoisomerase is sensitive to inhibition by
      coumermycin A1 (50% inhibitory concentration, 32 microM) but insensitive to five
      other previously reported topoisomerase inhibitors. This work provides the point
      of departure for studies of the mechanism of function of MCV topoisomerase and
      the development of medically useful inhibitors.

PMID- 9525671
TI  - Mutational analysis of the rous sarcoma virus DR posttranscriptional control
      element.
AB  - The direct repeat (DR) sequences flanking the src gene in Rous sarcoma virus are
      essential posttranscriptional control elements; at least one copy of this
      sequence is necessary for cytoplasmic accumulation of unspliced viral RNA. These
      sequences promote Rev-independent human immunodeficiency virus type 1 expression,
      suggesting they act as constitutive transport elements (CTEs). To determine which
      regions of this sequence are critical for CTE function, mutations in the
      downstream DR were generated and tested in a viral deletion construct lacking src
      and the upstream DR. Two single-point mutations and three different clustered
      mutations caused substantial reductions in reverse transcriptase activity, Gag
      protein levels, and unspliced viral RNA in the cytoplasm. Three conserved regions
      of the CTE, including nucleotides 8844 to 8847, 8862 to 8864, and 8868 to 8870,
      were most sensitive to inactivation by mutagenesis.

PMID- 9525672
TI  - Mutations of the human immunodeficiency virus type 1 p6Gag domain result in
      reduced retention of Pol proteins during virus assembly.
AB  - One of the crucial steps in the assembly of the human immunodeficiency virus type
      1 (HIV-1) and other retroviruses is the incorporation and retention of all the
      key viral enzymes in released virions. The viral enzymes protease, reverse
      transcriptase, and integrase of HIV-1 are initially synthesized as Gag-Pol fusion
      polyproteins. It has been shown that the incorporation of Gag-Pol polyproteins
      during virus assembly requires the Gag domains that are shared by the Gag and Gag
      Pol precursors. We now report that truncation of the C-terminal p6 domain of HIV
      1 Gag, which is present in the Gag precursor but not in the Gag-Pol precursor,
      drastically reduced the amount of Pol proteins in the mutant virions. Mutations
      in the lentivirus conserved motif P(T/S)APP in p6 also drastically reduced the
      amount of Pol proteins in mutant virions. The steady-state levels of Gag-Pol
      precursors and cleaved Pol proteins in the transfected cells were not affected by
      mutations in p6. The incorporation of unprocessed Gag-Pol precursors into p6
      mutant virions was detected when the viral protease was mutated, suggesting that
      the interactions among mutant Gag molecules and Gag-Pol precursors were not
      significantly affected. These results suggest that the p6 domain of HIV-1 Gag may
      play an important role in recruiting or retaining cleaved Pol proteins during
      virus assembly.

PMID- 9525674
TI  - The entire nucleotide sequence of friend-related and paralysis-inducing PVC-441
      murine leukemia virus (MuLV) and its comparison with those of PVC-211 MuLV and
      Friend MuLV.
AB  - PVC-441 murine leukemia virus (MuLV) is a member of the PVC group of Friend MuLV
      (F-MuLV)-derived neuropathogenic retroviruses. In order to determine the
      molecular basis for the difference in neuropathogenicity between PVC-441 and the
      previously characterized PVC-211 MuLVs, the entire nucleotide sequence of PVC-441
      MuLV was determined and compared with those of PVC-211 and F-MuLV. The results
      suggest that PVC-441 and PVC-211 MuLVs were formed as a result of random
      mutations of F-MuLV and developed differently. The distinct pathogenicities of
      PVC-441 and PVC-211 MuLVs were maintained in the viruses regenerated from their
      molecular clones, and the sequences responsible for the pathological differences
      observed can be localized to the env gene. The amino acid sequence of PVC-441
      deduced from its nucleotide sequence revealed a number of differences from PVC
      211, the most striking of which was a difference at position 129 of the SU
      proteins in the two viruses. Host range studies with a brain capillary
      endothelial cell line (RTEC-6) and Chinese hamster ovary cells (CHO-K1) revealed
      that PVC-441, like PVC-211, could infect these cells but its efficiency of
      infection was lower than that of PVC-211. These results may account for the
      difference in neuropathogenicity between PVC-441 and PVC-211.

PMID- 9525673
TI  - Virological and molecular demonstration of human immunodeficiency virus type 2
      vertical transmission.
AB  - To demonstrate that human immunodeficiency virus type 2 (HIV-2) mother-to-child
      transmission exists, HIV-2 isolates were obtained from both an asymptomatic
      mother (HIV-2 strain ARM), and her child (HIV-2 strain SAR), who had a diagnosis
      of AIDS. To determine their biological phenotype, primary isolates were used to
      infect various primary mononuclear cells and cell lines. HIV-2 ARM replicates in
      primary cells and Jurkat-tat, while HIV-2 SAR infects these cells plus SupT1,
      which led us to classify HIV-2 ARM as a slow/low virus and HIV-2 SAR as having an
      intermediate (slow/low-3) phenotype. Molecular analysis of the env region
      corresponding to gp125 was performed. Viral DNA was cloned, sequenced, and used
      to construct phylogenetic trees. The DNA sequence analysis demonstrated an
      overall nucleotide diversity of 7.6%. The results present evidence that the
      child's strain is more virulent than the mother's strain, which is in agreement
      with the immunodeficiency of the child. The phylogenetic trees that were
      constructed demonstrate that the two isolates cluster together, being closer to
      each other than to any other isolate described until now.

PMID- 9525675
TI  - Neutralizing antibodies in sera from macaques infected with chimeric simian-human
      immunodeficiency virus containing the envelope glycoproteins of either a
      laboratory-adapted variant or a primary isolate of human immunodeficiency virus
      type 1.
AB  - The magnitude and breadth of neutralizing antibodies raised in response to
      infection with chimeric simian-human immunodeficiency virus (SHIV) in rhesus
      macaques were evaluated. Infection with either SHIV-HXB2, SHIV-89.6, or SHIV
      89.6PD raised high-titer neutralizing antibodies to the homologous SHIV (SHIV
      89.6P in the case of SHIV-89.6PD-infected animals) and significant titers of
      neutralizing antibodies to human immunodeficiency virus type 1 (HIV-1) strains MN
      and SF-2. With few exceptions, however, titers of neutralizing antibodies to
      heterologous SHIV were low or undetectable. The antibodies occasionally
      neutralized heterologous primary isolates of HIV-1; these antibodies required >40
      weeks of infection to reach detectable levels. Notable was the potent
      neutralization of the HIV-1 89.6 primary isolate by serum samples from SHIV-89.6
      infected macaques. These results demonstrate that SHIV-HXB2, SHIV-89.6, and SHIV
      89.6P possess highly divergent, strain-specific neutralization epitopes. The
      results also provide insights into the requirements for raising neutralizing
      antibodies to primary isolates of HIV-1.

PMID- 9525676
TI  - Evidence for cooperation between murine leukemia virus Env molecules in mixed
      oligomers.
AB  - A retroviral Env molecule consists of a surface glycoprotein (SU) complexed with
      a transmembrane protein (TM). In turn, these complexes are grouped into oligomers
      on the surfaces of the cell and of the virion. In the case of murine leukemia
      viruses (MuLVs), the SU moieties are polymorphic, with SU proteins of different
      viral isolates directed towards different cell surface receptors. During
      maturation of the released virus particle, the 16 C-terminal residues of TM (the
      R peptide or p2E) are removed from the protein by the viral protease; this
      cleavage is believed to activate the membrane-fusing potential of MuLV Env. We
      have tested the possibility that different MuLV Env proteins in the same cell can
      interact with each other, both physically and functionally, in mixed oligomers.
      We found that coexpressed Env molecules can be precipitated out of cell lysates
      by antiserum which reacts with only one of them. Furthermore, they can evidently
      cooperate with each other: if one Env species lacks the R peptide, then it can
      apparently induce fusion if the SU protein of the other Env species encounters
      its cognate receptor on the surface of another cell. This functional interaction
      between different Env molecules has a number of implications with respect to the
      mechanism of induction of membrane fusion, for the genetic analysis of Env
      function, and for the design of targeted retroviral vectors for gene therapy.

PMID- 9525678
TI  - Physiological knockout of the envelope gene of the single-copy ERV-3 human
      endogenous retrovirus in a fraction of the Caucasian population.
AB  - ERV-3 is an evolutionarily conserved single-copy human endogenous retrovirus with
      a coding envelope gene potentially involved in important placental functions. We
      have investigated the sequence variability of this gene among 150 unrelated
      Caucasian individuals and found eight polymorphic sites. One of them corresponds
      to the introduction of a stop codon resulting in the production of a severely
      truncated ERV-3 envelope protein lacking both the fusion peptide and the
      immunosuppressive domain of the protein. The stop codon is observed in a
      homozygous state in approximately 1% of Caucasian individuals without evidence
      for counterselection, thus precluding the involvement of any essential function
      of the gene in placental implantation and development. This natural knockout
      provides a mean to investigate other potential roles for this otherwise highly
      conserved gene.

PMID- 9525677
TI  - The carboxyl-terminal region of the human papillomavirus type 16 E1 protein
      determines E2 protein specificity during DNA replication.
AB  - The mechanism of DNA replication is conserved among papillomaviruses. The virus
      encoded E1 and E2 proteins collaborate to target the origin and recruit host DNA
      replication proteins. Expression vectors of E1 and E2 proteins support homologous
      and heterologous papillomaviral origin replication in transiently transfected
      cells. Viral proteins from different genotypes can also collaborate, albeit with
      different efficiencies, indicating a certain degree of specificity in E1-E2
      interactions. We report that, in the assays of our study, the human
      papillomavirus type 11 (HPV-11) E1 protein functioned with the HPV-16 E2 protein,
      whereas the HPV-16 E1 protein exhibited no detectable activity with the HPV-11 E2
      protein. Taking advantage of this distinction, we used chimeric E1 proteins to
      delineate the E1 protein domains responsible for this specificity. Hybrids
      containing HPV-16 E1 amino-terminal residues up to residue 365 efficiently
      replicated either viral origin in the presence of either E2 protein. The
      reciprocal hybrids containing amino-terminal HPV-11 sequences exhibited a high
      activity with HPV-16 E2 but no activity with HPV-11 E2. Reciprocal hybrid
      proteins with the carboxyl-terminal 44 residues from either E1 had an
      intermediate property, but both collaborated more efficiently with HPV-16 E2 than
      with HPV-11 E2. In contrast, chimeras with a junction in the putative ATPase
      domain showed little or no activity with either E2 protein. We conclude that the
      E1 protein consists of distinct structural and functional domains, with the
      carboxyl-terminal 284 residues of the HPV-16 E1 protein being the primary
      determinant for E2 specificity during replication, and that chimeric exchanges in
      or bordering the ATPase domain inactivate the protein.

PMID- 9525679
TI  - The U3 promoter and the nef gene of simian immunodeficiency virus (SIV) smmPBj1.9
      do not confer acute pathogenicity upon SIVagm.
AB  - Two chimeric proviruses comprising the U3 promoter and the nef gene of simian
      immunodeficiency virus (SIV) smmPBj1.9 in addition to other genomic regions of
      SIVagm3mc from African green monkeys (Cercopithecus aethiops) were constructed.
      The derived chimeric viruses (SIVagm3mc/SIVsmmPBj1.9) were both able to replicate
      in nonstimulated peripheral blood leukocytes from pig-tailed macaques (Macaca
      nemestrina), a biological property often correlated with acute pathogenicity.
      However, only one of the chimeric viruses was acutely pathogenic, inducing a
      rapid depletion of the peripheral CD4+ T cells in two infected pig-tailed
      macaques within 10 days after infection in a manner similar to infection with
      SIVsmmPBj1.9 itself. The other chimeric virus actively replicated during the
      first 8 weeks after experimental infection of two pig-tailed macaques but induced
      neither acute disease nor CD4+ T-cell depletion for 113 weeks after infection.
      Thus, the U3 promoter and the nef gene of SIVsmmPBj1.9 alone appear to be
      insufficient to confer acute pathogenicity to SIVagm3mc.

PMID- 9525680
TI  - cis-Acting sequences required for simian foamy virus type 1 vectors.
AB  - We have constructed a series of vectors based on simian foamy virus type 1 (SFV
      1) to define the minimum cis-acting elements required for gene transfer. To
      characterize these vectors, we inserted the coding sequence of the bacterial lacZ
      gene linked to the cytomegalovirus immediate-early gene promoter. Introduction of
      a deletion mutation in the leader region between the 5' long terminal repeat and
      the start of the gag gene at position 1659 to 1694 completely abrogated gene
      transfer by the SFV-1 vector. Deletion of 39 nucleotides from position 1692 to
      1731 in the leader region resulted in a significant reduction in the transducing
      particle titer. Furthermore, we have identified a second cis-acting element
      located at the 3' end of the pol gene between position 6486 and 6975 to be
      critical for SFV-1 vector transduction. These results identify the two important
      cis-acting elements required for SFV-1 vector construction, and the finding of a
      cis-acting element in the pol gene is unique among retroviruses.

PMID- 9525681
TI  - Adenovirus internalization and infection require dynamin.
AB  - The cell receptors that facilitate adenovirus internalization into cells have
      been identified; however, the infectious pathway of virus entry has not been
      established. Adenovirus entry and infection were examined in HeLa cells lacking
      or overexpressing mutant dynamin, a protein that specifically regulates clathrin
      mediated endocytosis. Expression of mutant dynamin significantly reduced
      adenovirus internalization and gene delivery, indicating a functional requirement
      for this molecule. These findings are consistent with virus entry via the
      clathrin-coated pit pathway.

PMID- 9525682
TI  - Cleavage of human immunodeficiency virus type 1 proteinase from the N-terminally
      adjacent p6* protein is essential for efficient Gag polyprotein processing and
      viral infectivity.
AB  - Maturation of infectious human immunodeficiency virus (HIV) particles requires
      proteolytic cleavage of the structural polyproteins by the viral proteinase (PR),
      which is itself encoded as part of the Gag-Pol polyprotein. Expression of
      truncated PR-containing sequences in heterologous systems has mostly led to the
      autocatalytic release of an 11-kDa species of PR which is capable of processing
      all known cleavage sites on the viral precursor proteins. Relatively little is
      known about cleavages within the nascent virus particle, on the other hand, and
      controversial results concerning the active PR species inside the virion and the
      relative activities of extended PR species have been reported. Here, we report
      that HIV type 1 (HIV-1) particles of four different strains obtained from
      different cell lines contain an 11-kDa PR, with no extended PR proteins
      detectable. Furthermore, mutation of the N-terminal PR cleavage site leading to
      production of an N-terminally extended 17-kDa PR species caused a severe defect
      in Gag polyprotein processing and a complete loss of viral infectivity. We
      conclude that N-terminal release of PR from the HIV-1 polyprotein is essential
      for viral replication and suggest that extended versions of PR may have a
      transient function in the proteolytic cascade.

PMID- 9525683
TI  - Alanine substitutions of polar and nonpolar residues in the amino-terminal domain
      of CCR5 differently impair entry of macrophage- and dualtropic isolates of human
      immunodeficiency virus type 1.
AB  - Multiple extracellular domains of the CC-chemokine receptor CCR5 are important
      for its function as a human immunodeficiency virus type 1 (HIV-1) coreceptor. We
      have recently demonstrated by alanine scanning mutagenesis that the negatively
      charged residues in the CCR5 amino-terminal domain are essential for gp120
      binding and coreceptor function. We have now extended our analysis of this domain
      to include most polar and nonpolar amino acids. Replacement of alanine with all
      four tyrosine residues and with serine-17 and cysteine-20 decrease or abolish
      gp120 binding and CCR5 coreceptor activity. Tyrosine-15 is essential for viral
      entry irrespective of the test isolate. Substitutions at some of the other
      positions impair the entry of dualtropic HIV-1 isolates more than that of
      macrophagetropic ones.

PMID- 9525684
TI  - T-cell lymphoma caused by herpesvirus saimiri C488 independently of ie14/vsag, a
      viral gene with superantigen homology.
AB  - The immediate-early gene ie14/vsag of herpesvirus saimiri has homology with
      murine superantigens. We compared the pathogenesis of infection with either
      ie14/vsag deletion mutants or wild-type virus C488 in cottontop tamarin monkeys
      (Saguinus oedipus). Two weeks after infection, all animals developed acute T-cell
      lymphomas independently of the presence of the viral ie14/vsag gene.

PMID- 9525685
TI  - Persistent antibody responses but declining cytotoxic T-lymphocyte responses to
      multiple human immunodeficiency virus type 1 antigens in a long-term
      nonprogressing individual with a defective p17 proviral sequence and no
      detectable viral RNA expression.
AB  - Long-term nonprogressor AD-18 has been infected with human immunodeficiency virus
      type 1 (HIV-1) for at least 16 years. During the past 5 years, he has had
      undetectable levels of plasma viremia, and HIV-1 cannot be isolated from him.
      Sequencing of proviral DNA indicates that the only HIV-1 sequences that can be
      identified in AD-18 have gross defects in the p17-encoding regions of the gag
      gene (Y. Huang, L. Zhang, and D. D. Ho, Virology 240:36-49, 1998). However, AD-18
      has strong, sustained antibody responses to several HIV-1 antigens, including
      p17. Cytotoxic T-lymphocyte responses to Env and Gag antigens have gradually
      diminished over the past 4 years, at a time when the titers of antibodies to the
      same proteins have remained stable. We discuss what these observations might mean
      for the generation and maintenance of immunological memory.

PMID- 9525686
TI  - CD4-immunoglobulin G2 protects Hu-PBL-SCID mice against challenge by primary
      human immunodeficiency virus type 1 isolates.
AB  - CD4-immunoglobulin G2 (IgG2) is a fusion protein comprising human IgG2 in which
      the Fv portions of both heavy and light chains have been replaced by the V1 and
      V2 domains of human CD4. Previous studies found that CD4-IgG2 potently
      neutralizes a broad range of primary human immunodeficiency virus type 1 (HIV-1)
      isolates in vitro and ex vivo. The current report demonstrates that CD4-IgG2
      protects against infection by primary isolates of HIV-1 in vivo, using the hu-PBL
      SCID mouse model. Passive administration of 10 mg of CD4-IgG2 per kg of body
      weight protected all animals against subsequent challenge with 10 mouse
      infectious doses of the laboratory-adapted T-cell-tropic isolate HIV-1(LAI),
      while 50 mg of CD4-IgG2 per kg protected four of five mice against the primary
      isolates HIV-1(JR-CSF) and HIV-1(AD6). In contrast, a polyclonal HIV-1 Ig
      fraction exhibited partial protection against HIV-1(LAI) at 150 mg/kg but no
      significant protection against the primary HIV-1 isolates. The results
      demonstrate that CD4-IgG2 effectively neutralizes primary HIV-1 isolates in vivo
      and can prevent the initiation of infection by these viruses.

PMID- 9525687
TI  - Induction of mucosal B-cell memory by intramuscular inoculation of mice with
      rotavirus.
AB  - We investigated the capacity of intramuscular (i.m.) immunization with
      heterologous-host rotavirus (simian strain RRV) to induce mucosal virus-specific
      memory B cells in mice. We found that prior i.m. immunization enhanced the
      magnitude of mucosal virus-specific immunoglobulin A (IgA) production but did not
      alter the site and timing of induction of virus-specific IgA responses after
      challenge.

PMID- 9525688
TI  - Two closely related but distinct retroviruses are associated with walleye
      discrete epidermal hyperplasia.
AB  - Walleye discrete epidermal hyperplasia (WEH) is a hyperproliferative skin disease
      that is prevalent on adult walleye fish throughout North America. We have
      identified two retroviruses associated with WEH, designated here as walleye
      epidermal hyperplasia virus type 1 and type 2 (WEHV1 and WEHV2), that are closely
      related to one another (77% identity) and to walleye dermal sarcoma virus (64%
      identity) within the polymerase region. WEHV1 and/or WEHV2 viral DNA was readily
      detected by PCR in hyperplastic tissue samples, but only low levels of viral DNA
      were detected in uninvolved skin. Southern blot analysis showed one to three
      copies of integrated WEHV2 viral DNA in lesions but did not detect WEHV2 viral
      DNA in uninvolved skin from the same fish. Northern blots detected abundant
      levels of WEHV1 and/or WEHV2 virion RNA transcripts of approximately 13 kb in
      hyperplastic tissue, but virion RNA was not observed in uninvolved skin and
      muscle. These results suggest that WEHV1 and WEHV2 are the causative agents of
      discrete epidermal hyperplasia.

PMID- 9525689
TI  - Pneumococcal bacteriophage Cp-1 encodes its own protease essential for phage
      maturation.
AB  - The major capsid protein of the pneumococcal phage Cp-1 that accounts for 90% of
      the total protein found in the purified virions is synthesized by
      posttranslational processing of the product of the open reading frame (ORF) orf9.
      Cloning of different ORFs of the Cp-1 genome in Escherichia coli and
      Streptococcus pneumoniae combined with Western blot analysis of the expressed
      products led to the conclusion that the product of orf13 is an endoprotease that
      cleaves off the first 48 amino acid residues of the major head protein. This
      protease appears to be a key enzyme in the morphopoietic pathway of the Cp-1
      phage head. To our knowledge, this is the first case of a bacteriophage infecting
      gram-positive bacteria that encodes a protease involved in phage maturation.

PMID- 9525691
TI  - The CAR1 gene encoding a cellular receptor specific for subgroup B and D avian
      leukosis viruses maps to the chicken tvb locus.
AB  - Host susceptibility to subgroup B, D, and E avian leukosis viruses (ALV) is
      determined by specific alleles of the chicken tvb locus. Recently, a chicken gene
      that encodes a cellular receptor, designated CAR1, specific for subgroups B and D
      ALV was cloned, and it was proposed that this gene was the s3 allele of tvb (J.
      Brojatsch, J. Naughton, M. M. Rolls, K. Zingler, and J. A. T. Young, Cell 87:845
      855, 1996). We now report that in a backcross derived from an F1 (Jungle Fowl x
      White Leghorn [WL]) male mated with inbred WL females, the cloned ALV receptor
      gene cosegregated with two markers linked to tvb. The two markers used were a
      tvb(s1)-specific antigen recognized by the chicken R2 alloantiserum and
      restriction fragment length polymorphisms associated with the expressed sequence
      tag com152e. With all three markers, no crossovers were observed among 52
      backcross progeny tested and LOD linkage scores of 15.7 were obtained. These data
      demonstrate that CAR1 is the subgroup B and D ALV susceptibility gene located at
      tvb(s3).

PMID- 9525692
TI  - Introduction. An Oscar for TGF-beta and its performance in the kidney.

PMID- 9525690
TI  - The TAATGARAT motif in the herpes simplex virus immediate-early gene promoters
      can confer both positive and negative responses to cellular octamer-binding
      proteins when it is located within the viral genome.
AB  - The TAATGARAT motif in the herpes simplex virus (HSV) immediate-early (IE) gene
      promoters plays a key role in their activation by the Oct-1-Vmw65 complex, but
      its role in mediating inhibitory effects of cellular octamer-binding proteins is
      less clear. We have used indicator viruses containing reporter constructs with
      different IE promoters driving a reporter beta-galactosidase gene within the
      viral genome to investigate this. We showed that deletion of the upstream IE
      promoter region containing the TAATGARAT motifs abolishes the inhibitory effect
      of the cellular octamer-binding proteins Oct-2.4 and Oct-2.5 on the viral IE
      promoter. This inhibitory effect can be restored by addition of a single
      TAATGARAT motif to the minimal promoter within the viral genome. Hence, the
      TAATGARAT motif can indeed mediate both positive and negative effects of cellular
      transcription factors when it is located within the viral genome.

PMID- 9525693
TI  - Molecular and cell biology of TGF-beta.
AB  - The TGF-betas are a remarkable set of peptides consisting of three highly
      homologous isoforms, TGF-beta 1, 2, and 3. Distinguished initially for their
      ability to inhibit the growth of most epithelial and hematopoietic cells and to
      regulate the production of extracellular matrix by mesenchymal cells, these
      peptides are now known to act via autocrine, paracrine, and endocrine modes to
      control a wide variety of developmental processes and to play key roles in the
      pathogenesis of many diseases including especially fibrotic diseases, parasitic
      diseases, autoimmune diseases, and carcinogenesis. The activity of these peptides
      is under tight control by processes including regulation of the expression of the
      isoforms and their receptors and of the trafficking and activation of their
      latent forms.

PMID- 9525694
TI  - TGF-beta receptors and signalling mechanisms.
AB  - Transforming growth factor-beta (TGF-beta) is the founding member of a large
      superfamily of related growth and differentiation factors that include bone
      morphogenetic proteins and activins. TGF-beta signals through two related
      transmembrane ser/thr kinase receptors, the type I and type II receptors.
      Signalling is initiated when the ligand binds to the type II receptor which is
      followed by recruitment of the type I receptor into a heteromeric complex. Within
      the complex the type II receptor transphosphorylates and activates the type I
      receptor kinase which targets downstream signalling components of the pathway.
      Proteins related to the Drosophila gene Mothers against dpp (MAD) are critical
      downstream substrates of the type I kinase. The vertebrate members of the MAD
      related family, termed Smad2 and Smad3, interact specifically with the TGF-beta
      type I receptor and are phosphorylated on the last two serines of a conserved C
      terminal SSXS motif. This phosphorylation induces association between these
      receptor-regulated Smads and Smad4 followed by translocation of the heteromeric
      complex to the nucleus. In the nucleus, heteromeric complexes of Smads can
      interact with DNA and with specific DNA binding transcription factors to elicit
      gene responses to TGF-beta. Thus TGF-beta signalling involves a direct pathway
      from the cell surface receptors to the nucleus. Recently, a novel mechanism to
      negatively regulate TGF-beta signalling was described that involves another class
      of MADR proteins. These anti-MADR proteins potently inhibit TGF-beta signalling
      by functioning as direct antagonists of the TGF-beta receptor type I kinase
      domain.

PMID- 9525695
TI  - Mechanisms of TGF-beta-induced cell cycle arrest.
AB  - Mitogenic growth factors stimulate cell growth by initiating a signaling cascade
      leading to the activation of the cyclin-dependent kinases (cdks), phosphorylation
      of pRb, and subsequent entry of the cell into the S phase. Transforming growth
      factor-beta (TGF-beta) is a potent antimitogen in a wide variety of cells and is
      postulated to inhibit cell cycle progression by blocking the late G1 activation
      of the cdks, thereby preventing pRb phosphorylation and S phase entry. The loss
      of TGF-beta sensitivity in many transformed cells coupled with recent data
      demonstrating a deregulation of cyclins, cdks, and cdk inhibitors in many types
      of cancer has attracted much attention to the molecular mechanism of TGF-beta
      mediated growth arrest. Despite these recent advances, further research is
      required to elucidate how these effects of TGF-beta on the cyclins, cdks, and cdk
      inhibitors are linked to the TGF-beta receptor complex and the Smad proteins.

PMID- 9525696
TI  - Role of TGF-beta in vascular development and vascular reactivity.
AB  - Transforming growth factor-beta (TGF-beta) is the prototypic member of a large
      family of structurally related proteins. Three vertebrate TGF-beta isoforms have
      been identified and termed TGF-beta1, TGF-beta2, and TGF-beta3, respectively. In
      addition, two receptors of the serine/threonine kinase family termed type I and
      II have also been identified. In this review, we focused our attention on the
      effects of TGF-beta on vascular development and vascular reactivity. The critical
      role of the TGF-beta1 and the TGF-beta type II receptor in blood vessel formation
      in the yolk sac has been demonstrated by gene deletion experiments. Recent
      investigations have also shown that isoforms of TGF-beta play a critical role in
      smooth muscle cell differentiation. And, finally, a role for TGF-beta1 in the
      regulation of vascular tone and reactivity has been suggested by studies
      demonstrating that TGF-beta1 can inhibit the production of potent vasodilators
      (such as nitric oxide) and stimulate the production of potent vasoconstrictors
      (such as endothelin). Taken together, these studies suggest that TGF-beta plays a
      critical role in blood vessel development and vascular function.

PMID- 9525697
TI  - TGF-beta in renal development and renal growth.
AB  - Organogenesis of the metanephric kidney is regulated by a number of polypeptide
      growth factors. Members of the TGF-beta family of growth factors have been shown
      to be produced in kidney during its development. Available evidence suggests that
      some of these members play key roles in metanephrogenesis by regulating the
      process of ureteric bud arborization. The regeneration of the S3 segment of the
      proximal tubule that occurs following ischemic injury recapitulates in many ways
      the renal developmental paradigm. The expression of TGF-beta in regenerating
      kidney is tightly regulated postischemia. We suggest that TGF-beta plays a key
      role in the repair process following injury and mediates some of the cellular
      events common to both regeneration and nephrogenesis.

PMID- 9525698
TI  - Localization of TGF-beta and its receptors in the kidney.
AB  - This paper reviews the expression and localization of proteins of the TGF-beta
      system in the kidney, i.e. TGF-beta isoforms, latent TGF-beta binding protein,
      and receptors. There is heterogeneity of TGF-beta isoforms, binding proteins and
      receptors. TGF-betas are more evenly distributed among different segments of the
      nephron than TGF-beta receptors, and are expressed by almost all cell types in
      the kidney. The spatial distribution of TGF-beta and its signaling receptor may
      help to better understand the biologic function of TGF-beta in the kidney.

PMID- 9525699
TI  - Lessons from TGF-beta transgenic mice.
AB  - Aberrant expression of TGF-beta and/or receptor/signaling function is present in
      a wide variety of disease processes. Overexpression of TGF-beta isoforms in
      transgenic mice using tissue-specific promoters has provided model systems to
      study the effects of increased activity of TGF-beta in the intact organism. We
      will review the pertinent features of some of these models, and discuss new
      insights provided by these studies into regulation and role of TGF-beta in health
      and disease.

PMID- 9525700
TI  - TGF-beta knockout and dominant-negative receptor transgenic mice.
AB  - Use of homologous recombination and transgenic technologies have provided mouse
      models to study the physiological roles of the three mammalian TGF-beta isoforms,
      and their regulation in the context of the intact animal. Mice harboring null
      mutations for TGF-beta isoforms demonstrate that each exerts discrete
      nonoverlapping functions during development. TGF-beta1 null mice reveal a crucial
      role for this cytokine in modulation of the immune system, with evidence for
      altered development, activation and function of various immune cell populations.
      New approaches to tissue- and cell-restricted disruption of TGF-beta signaling
      pathways in transgenic mice carrying dominant-negative mutant TGF-beta receptors
      will be discussed.

PMID- 9525701
TI  - TGF-beta in glomerular disease.
AB  - Transforming growth factor-beta (TGF-beta) is an important cytokine in glomerular
      disease. Its major role may be to mediate extracellular matrix deposition, by
      both increasing the synthesis of matrix components and by reducing their
      degradation. Strong evidence supports the functional role for TGF-beta in
      mesangial matrix expansion. However, TGF-beta may also have other important
      functions in the glomerulus, including the regulation of cell proliferation,
      hypertrophy, and survival (apoptosis), as well as modulation of the local and
      systemic immune response.

PMID- 9525702
TI  - Link between angiotensin II and TGF-beta in the kidney.
AB  - Glomerulosclerosis and tubulointerstitial fibrosis are common morphological
      correlates of many end-stage kidneys. There is ample evidence that transforming
      growth factor-beta (TGF-beta) plays a major role in these alterations by directly
      stimulating synthesis of many extracellular matrix components and reducing
      collagenase production, finally leading to renal scarring. Although many factors
      may induce TGF-beta expression in the kidney, one very interesting aspect is the
      link between angiotensin II (ANG II) and TGF-beta. Originating from observations
      in vascular smooth muscle cells, there are now several additional studies showing
      that ANG II stimulates TGF-beta expression in the kidney. Although cell culture
      studies have convincingly demonstrated that the vasoactive peptide directly
      stimulates transcription as well as bioactivation of TGF-beta, the in vivo
      evidence is more indirect. Nevertheless, there are several pathophysiological
      situations including unilateral ureteral obstruction, chronic cyclosporin A
      nephrotoxicity, various models of hypertension, and probably diabetic nephropathy
      in which ANG II-mediated TGF-beta induction has been demonstrated to play an
      important role in the progression of the disease. The fascinating aspect of this
      relationship between ANG II and TGF-beta is the fact that hemodynamic changes as
      well as structural changes are linked together generating a unifying model of
      progression of chronic renal failure with ANG II as the key player. Angiotensin
      converting enzyme (ACE) inhibitor and the more recently introduced AT1-receptor
      blocker may be potential drugs to interfere with this ANG II-mediated TGF-beta
      expression. Therefore, these drugs should not only be considered as
      antihypertensive medications, but should rather be viewed as renoprotective
      substances influencing renal remodeling by preventing local TGF-beta expression.

PMID- 9525703
TI  - TGF-beta and regulation of interstitial nephritis.
AB  - TGF-beta1 has been implicated as a profibrotic growth factor in the bulk of
      published experimental work regarding the actions of this cytokine in kidney
      disease. Such investigations have spanned a methodologic spectrum from in vivo
      analyses to cell culture work with purified growth factors and analyses of gene
      expression. Important correlative work using clinical specimens has established
      the presence of augmented TGF-beta expression in renal diseases characterized by
      excessive sclerosis or fibrosis. While in the aggregate this information supports
      a compelling argument in favor of TGF-beta having a predominant effect to
      accelerate progressive renal failure, the cytokine clearly also demonstrates
      effects which would tend to abrogate renal injury. We provide a summary of
      published and new experimental data outlining immunosuppressive and 'renal
      protective' actions of TGF-beta1.

PMID- 9525704
TI  - Potential role of TGF-beta in diabetic nephropathy.
AB  - Renal injury in diabetes mellitus is a major cause of morbidity and mortality.
      Several manifestations of diabetic nephropathy may be a consequence of altered
      production and/or response to cytokines or growth factors. Transforming growth
      factor-beta (TGF-beta) is one such factor because it promotes renal cell
      hypertrophy and regulates the production of extracellular matrix molecules. In
      addition, high ambient glucose increases TGF-beta1 mRNA and protein level in
      cultured proximal tubular cells and glomerular epithelial and mesangial cells.
      Neutralizing anti-TGF-beta antibodies or antisense TGF-beta1
      oligodeoxynucleotides prevents the hypertrophic effects of high glucose and the
      stimulation of matrix synthesis in renal cells. Several reports have described
      overexpression of TGF-beta in the glomeruli and tubulointerstitium of
      experimental and human diabetes mellitus. We recently provided evidence that the
      kidney in diabetic patients displays net renal production of immunoreactive TGF
      beta1, whereas there is net renal extraction in nondiabetic subjects. We also
      demonstrated that short-term treatment of streptozotocin-diabetic mice with
      neutralizing monoclonal antibody directed against TGF-beta significantly reduces
      kidney weight and glomerular hypertrophy, and attenuates the increase in
      extracellular matrix mRNA levels. The factors that mediate increased renal TGF
      beta activity involve hyperglycemia per se and the intermediary action of other
      potent mediators such as angiotensin II, thromboxane, endothelins, and platelet
      derived growth factor.

PMID- 9525705
TI  - TGF-beta in renal allograft rejection.
AB  - The role of TGF-beta in pathological processes in the transplanted kidney is
      beginning to be investigated both in animal models and in humans. In both
      settings in acute cell-mediated rejection, TGF-beta, receptor, and message have
      all been documented to be elevated in the tubulointerstitium, likely a reflection
      of TGF-beta's role in recruiting leukocytes to areas of injury and downregulation
      of the inflammatory response. In chronic rejection, expression of TGF-beta,
      message, and induced proteins is elevated, especially in cortex. TGF-beta mRNA,
      unlike other inflammatory cytokine mRNAs, correlated very well with interstitial
      fibrosis, a hallmark of chronic rejection. Thus, a relationship between renal
      scarring and TGF-beta has been documented by most studies of transplant kidneys.
      Additionally, this growth factor also appears to have a role in the renal
      fibrosis associated with cyclosporine administration and perhaps in augmenting
      this drug's immunosuppressive effects.

PMID- 9525706
TI  - Experience in the surgical management of 82 symptomatic herniated thoracic discs
      and review of the literature.
AB  - OBJECT: The authors aimed to develop management strategies for the treatment of
      herniated thoracic discs and to define indications for selection of surgical
      approaches. Symptomatic thoracic discs requiring surgery are rare. Between 1971
      and 1995, 71 patients with 82 herniated thoracic discs were surgically treated by
      the authors. The treated group included 34 men and 37 women whose ages ranged
      from 19 to 75 years, with a mean age of 48 years. The most common sites of disc
      herniation requiring surgery were from T-8 to T-11. Evidence of antecedent trauma
      was present in 37% of the patients. Preoperative symptoms included pain
      (localized, axial, or radicular) in 54 (76%) of the 71 patients, evidence of
      myelopathy, that is, motor impairment in 43 (61%), hyperreflexia and spasticity
      in 41 (58%), sensory impairment in 43 (61%), and bladder dysfunction in 17 (24%).
      METHODS: Radiological diagnosis for the patients in this series was accomplished
      by means of myelography, computerized tomography myelography, or magnetic
      resonance imaging. Classification of the disc location into two groups reveals
      that 94% were centrolateral and 6% were lateral. Evidence of calcification was
      present in 65% of patients, and in 7% intradural extension was noted at surgery.
      Ten patients (14%) were found to have multiple herniations. Four surgical
      approaches were used for the removal of these 82 disc herniations: transthoracic
      in 49 (60%), transfacet pedicle-sparing in 23 (28%), lateral extracavitary in
      eight (10%), and transpedicular in two (2%). Postoperative evaluation revealed
      improvement or resolution of pain in 47 (87%) of 54, hyperreflexia and spasticity
      in 39 (95%) of 41, sensory changes in 36 (84%) of 43, bowel/bladder dysfunction
      in 13 (76%) of 17, and motor impairment in 25 (58%) of 43. Complications occurred
      in a total of 12 (14.6%) of 82 discs treated surgically. Major complications were
      seen in three patients and included perioperative death from cardiopulmonary
      compromise, instability requiring further surgery, and an increase in the
      severity of a preoperative paraparesis. CONCLUSIONS: Review of this series, with
      the attendant complications, together with evaluation of several contemporary
      thoracic disc series, has facilitated the authors' decision-making process when
      considering the comprehensive management of these patients, including the
      selection of a surgical approach.

PMID- 9525707
TI  - Vertebral artery injury in C1-2 transarticular screw fixation: results of a
      survey of the AANS/CNS section on disorders of the spine and peripheral nerves.
      American Association of Neurological Surgeons/Congress of Neurological Surgeons.
AB  - OBJECT: The 847 active members of the American Association of Neurological
      Surgeons/Congress of Neurological Surgeons (AANS/CNS) Section on Disorders of the
      Spine and Peripheral Nerves were surveyed to quantitate the risk of vertebral
      artery (VA) injury during C1-2 transarticular screw placement. METHODS: This
      retrospective study elicited the number of patients treated with transarticular
      screws, the number of screws placed, the incidence of VA injury and subsequent
      neurological deficit, and the management of known or suspected VA injury. Two
      hundred thirteen (25.1%) of the 847 surgeons responded. One hundred one
      respondents (47.4%) had placed a total of 2492 C1-2 transarticular screws in 1318
      patients. Thirty-one patients (2.4%) had known VA injuries and an additional 23
      patients (1.7%) were suspected of having injuries. However, only two (3.7%) of
      the 54 patients with known or suspected VA injuries exhibited subsequent
      neurological deficits and only one (1.9%) died of bilateral VA injury. Other
      iatrogenic complications included dural tears, screw fractures, screw breakout,
      fusion failure, infection, and suboccipital numbness. CONCLUSIONS: Including both
      known and suspected cases, the risk of VA injury was 4.1% per patient or 2.2% per
      screw inserted. The risk of neurological deficit from VA injury was 0.2% per
      patient or 0.1% per screw, and the mortality rate was 0.1%. The choice of
      management of intraoperative VA injuries was evenly divided between placing the
      patient under observation and initiating immediate postoperative angiography with
      possible balloon occlusion.

PMID- 9525708
TI  - Microsurgical treatment of arteriovenous malformations: analysis and comparison
      with stereotactic radiosurgery.
AB  - OBJECT: To compare microsurgical and stereotactic radiosurgical treatment of
      arteriovenous malformations (AVMs), the authors analyzed a prospective series of
      72 consecutive patients who were treated microsurgically for cerebral AVMs by one
      neurosurgeon. The authors then compared the results of microsurgical treatment
      with published results of stereotactic radiosurgical treatment of small AVMs.
      METHODS: Patients were categorized by age, gender, presentation, and preoperative
      neurological status. The AVMs were categorized by size, location, presence of
      deep venous drainage, and Spetzler-Martin grade. Outcome was assessed for
      angiographic obliteration, hemorrhage following treatment, presence of a new,
      persistent postoperative neurological deficit, and Glasgow Outcome Scale (GOS)
      score. Ordinal logistic regression was used to model the GOS score and to predict
      new postoperative deficits. Generalized estimating equations were used to compare
      published results of microsurgical and stereotactic radiosurgical treatment of
      AVMs. Kaplan-Meier event-free survival plots were generated to compare the two
      modalities with respect to hemorrhage following treatment. Overall, six patients
      (8.3%) exhibited a new persistent neurological deficit postoperatively. Sixty
      five patients (90.3%) had a GOS score of 5. Three patients were moderately
      disabled and four patients were severely disabled. No patient was observed to be
      in a vegetative state and there were no treatment-related deaths. Seventy-one
      patients (98.6%) underwent intra- or postoperative angiography. Total excision of
      the AVM was angiographically confirmed in 70 patients (98.6% of those who
      underwent angiography). To date no patient has suffered from hemorrhage since the
      microsurgical treatment. When analysis was confined to patients whose AVMs were
      smaller than 3 cm in maximum diameter, the authors found a 100% angiographic
      obliteration rate, no new postoperative neurological deficit, and a good recovery
      in all patients. An analysis of all patients with Spetzler-Martin Grades I to III
      resulted in a 100% rate of angiographic obliteration, one patient with a new
      postoperative neurological deficit, and good recovery in 93% of the patients.
      Size of the AVM, preoperative neurological status, and patient age are associated
      with GOS score (for all, p < 0.02). The Spetzler-Martin grading system as well as
      each component of this system are associated with the development of a new
      postoperative neurological deficit (for all, p < 0.01). For the entire series
      there were fewer postoperative hemorrhages and deaths than those mentioned in
      published series of small AVMs treated with stereotactic radiosurgery. When these
      patients and published series of patients with microsurgically treated AVMs
      classified as Grade I to III were compared with similar patients treated
      radiosurgically there were significantly fewer postoperative hemorrhages (odds
      ratio = 0.210, p = 0.001), fewer deaths (odds ratio = 0.659, p = 0.019), fewer
      new posttreatment neurological deficits (odds ratio = 0.464, p = 0.013), and a
      higher incidence of obliteration (odds ratio = 28.2, p = 0.001) for the
      microsurgical group. Lifetable analysis confirms the statistically significant
      difference in hemorrhage-free survival time between the two groups (p = 0.002).
      CONCLUSIONS: Based on this analysis, microsurgical treatment of Grades I to III
      AVMs is superior to stereotactic radiosurgery.

PMID- 9525709
TI  - Repair of carotid endarterectomy with a collagen-impregnated fabric graft.
AB  - Saphenous vein patch closure of carotid endarterectomies may decrease the risk of
      acute postoperative occlusion and recurrent stenosis. However, the disadvantages
      of a vein patch include postoperative rupture and pseudoaneurysm formation.
      OBJECT: The authors sought to assess the effectiveness of collagen-impregnated
      fabric grafts as substitutes for saphenous vein grafts. METHODS: In this report
      the authors prospectively analyzed 290 consecutive carotid endarterectomies in
      which a secondary closure was accomplished using a knitted double-velour graft.
      The 30-day major neurological morbidity and mortality rate was 1.7%. There were
      no postoperative occlusions or wound hematomas. The rate of recurrent carotid
      artery stenosis was less than 1%, and the graft site in one patient became
      infected. CONCLUSIONS: For surgeons who prefer a secondary closure of carotid
      endarterectomies, the synthetic graft may prove to be a viable alternative to a
      saphenous vein.

PMID- 9525710
TI  - Magnetic resonance imaging-documented extravasation as an indicator of acute
      hypertensive intracerebral hemorrhage.
AB  - OBJECT: The aim of this study was to determine the usefulness of magnetic
      resonance (MR) imaging-documented extravasation as an indicator of continued
      hemorrhage in patients with acute hypertensive intracerebral hemorrhage (ICH).
      METHODS: The authors studied 108 patients with acute hyperintensive ICH. Imaging
      modalities included noncontrast-enhanced computerized tomography (CT) scanning,
      gadolinium-enhanced MR imaging, and conventional cerebral angiography obtained
      within 6 hours after the onset of hemorrhage. A repeated CT scan was obtained
      within 48 hours to evaluate enlargement of the hematoma. Findings on MR imaging
      indicating extravasation, including any high-intensity signals on T1-weighted
      postcontrast images, were observed in 39 patients, and 17 of these also showed
      evidence of extravasation on cerebral angiography. The presence of extravasation
      on MR imaging was closely correlated with evidence of hematoma enlargement on
      follow-up CT scans (p < 0.001). CONCLUSIONS: Evidence of extravasation documented
      on MR imaging indicates persistent hemorrhage and correlates with enlargement of
      the hematoma.

PMID- 9525711
TI  - Postimaging brain distortion: magnitude, correlates, and impact on
      neuronavigation.
AB  - OBJECT: This prospective study was conducted to quantify brain shifts during open
      cranial surgery, to determine correlations between these shifts and image
      characteristics, and to assess the impact of postimaging brain distortion on
      neuronavigation. METHODS: During 48 operations, movements of the cortex on
      opening, the deep tumor margin, and the cortex at completion were measured
      relative to the preoperative image position with the aid of an image-guidance
      system. Bone surface offset was used to assess system accuracy and correct for
      registration errors. Preoperative images were examined for the presence of edema
      and to determine tumor volume, midline shift, and depth of the lesion below the
      skin surface. Results were analyzed for all cases together and separately for
      four tumor groups: 13 meningiomas, 18 gliomas, 11 nonglial intraaxial lesions,
      and six skull base lesions. For all 48 cases the mean shift of the cortex after
      dural opening was 4.6 mm, shift of the deep tumor margin was 5.1 mm, and shift of
      the cortex at completion was 6.7 mm. Each tumor group displayed unique patterns
      of shift, with significantly greater shift at depth in meningiomas than gliomas
      (p = 0.007) and significantly less shift in skull base cases than other groups (p
      = 0.003). Whereas the preoperative image characteristics correlating with shift
      of the cortex on opening were the presence of edema and depth of the tumor below
      skin surface, predictors of shift at depth were the presence of edema, the lesion
      volume, midline shift, and magnitude of shift of the cortex on opening.
      CONCLUSIONS: This study quantified intraoperative brain distortion, determined
      the different behavior of tumors in four pathological groups, and identified
      preoperative predictors of shift with which the reliability of neuronavigation
      may be estimated.

PMID- 9525712
TI  - Computerized tomography angiography of ruptured cerebral aneurysms: factors
      affecting time to maximum contrast concentration.
AB  - OBJECT: This study was conducted to assess the diagnostic value of three
      dimensional computerized tomography (3-D CT) angiography in demonstrating
      cerebral aneurysms in 42 consecutive patients presenting with acute subarachnoid
      hemorrhage (SAH). METHODS: To obtain the volume data for selective visualization
      of the cerebral arteries without enhancement of the venous system, the time delay
      was established between the injection of contrast medium and the start of
      scanning by using two different methods. The circulation time was calculated with
      Schad's formula in the first 13 cases, but the results were not satisfactory. In
      the 29 subsequent cases the time delay was established using a single-level
      dynamic CT prescan. The dynamic prescan demonstrated the statistical differences
      in peak time with regard to patient age, SAH grade, and the postresuscitation
      state after cardiopulmonary arrest. The 3-D CT angiograms were generated from the
      volume data by using a voxel transmission method. Computerized tomography
      angiography obtained after optimally adjusted time delay demonstrated the contour
      of the cerebral arteries in 97% of cases, and aneurysms were detected in 93%.
      Enhancement of the cavernous sinus and major cortical veins was avoided. Even in
      patients who suffered cardiopulmonary arrest, images of the major arteries were
      clearly demonstrated after resuscitation. CONCLUSIONS: In an emergency situation,
      CT angiography with a dynamic prescan may be an alternative to magnetic resonance
      angiography or digital subtraction angiography in the diagnosis of ruptured
      aneurysms. This modality would also be useful for the precise assessment of small
      aneurysms, blebs, and aneurysms adjacent to the cavernous sinus.

PMID- 9525713
TI  - Magnetic resonance cisternography for visualization of intracisternal fine
      structures.
AB  - OBJECT: To assess its usefulness in demonstrating cisternal anatomy, the authors
      investigated magnetic resonance (MR) cisternography in which a heavily T2
      weighted turbo spin-echo method was used to visualize normal anatomical fine
      structures and lesions in the basal cisterns in 20 healthy volunteers and 43
      patients. The authors applied peripheral pulse gating, which had been optimized
      to reduce artifacts in the cisterns attributable to cerebrospinal fluid (CSF)
      flow. METHODS: The detectability of each cranial nerve was determined in healthy
      volunteers. The first, second, and third nerves and the seventh-eighth nerve
      complex were clearly visualized in all participants; the fifth nerve was clearly
      seen in 80% and the sixth cranial nerve in 50%. The fourth nerve and the ninth
      through 12th nerves were difficult to identify individually, except in some
      volunteers. To reduce artifacts caused by fast CSF flow, we determined the delays
      as a function of the time elapsed between two consecutive peaks of pulse wave in
      a peripheral pulse gate (P-P interval) at which there was reversal of flow
      direction to minimize the CSF flow-related artifact. Using peripheral pulse
      gating and a time delay of 30% of the R-R interval, the authors succeeded in
      minimizing the CSF flow-related artifacts. Magnetic resonance cisternography
      appears to be very useful for demonstrating intracisternal fine anatomy and
      enhancing the contours of the juxtacisternal lesion. A minute amount of CSF
      interposed between lesions and normal structures such as nerves, vessels, or bone
      structures can be detected by means of this sequence. In patients with facial
      spasm, axial images and oblique coronal images obtained in a plane parallel to
      the seventh-eighth cranial nerve complex demonstrated vascular compression in all
      13 patients. The MR cisternography finding of compression was confirmed in all
      nine patients who underwent microvascular decompression. CONCLUSIONS: Magnetic
      resonance cisternography appears to show great promise for evaluation of patients
      with neurovascular compression or tumors in and around the basal cisterns; the
      procedure adds only a small amount of imaging time.

PMID- 9525714
TI  - Computerized tomography angiography in isolated third nerve palsies.
AB  - OBJECT: The goal of this study was to assess the value of computerized tomography
      (CT) angiography as a diagnostic tool in isolated oculomotor nerve palsies.
      METHODS: One hundred consecutive patients who presented with an isolated third
      nerve palsy were examined by CT angiography. This procedure was followed by
      conventional cerebral angiography in most patients in whom a vascular abnormality
      was noted on the CT angiography. Thus, all patients whose symptoms were caused by
      a compressive aneurysm were identified. The remaining patients were observed
      clinically to exclude the possibility that a missed cerebral aneurysm caused the
      isolated third nerve palsy. Eighteen patients harbored a cerebral aneurysm
      responsible for causing the isolated third nerve palsy. Most of the remaining
      patients experienced some degree of spontaneous recovery. There was no clinical
      evidence to indicate that a case of compressive cerebral aneurysm causing the
      isolated third nerve palsy had been missed on CT angiography. CONCLUSIONS:
      Computerized tomography angiography is a reliable diagnostic tool for use in the
      assessment of patients with an isolated third nerve palsy; it can identify the
      minority of patients in whom conventional cerebral angiography may be required.

PMID- 9525715
TI  - Intrauterine high-resolution magnetic resonance imaging in fetal hydrocephalus
      and prenatal estimation of postnatal outcomes with "perspective classification".
AB  - OBJECT: It is possible to diagnose hydrocephalus prenatally based on the
      morphological appearance of the fetus on neurodiagnostic images; however, the
      prognosis of this disease shows wide variation. The authors previously proposed a
      classification system for the prediction of postnatal outcome based on
      progression of hydrocephalus and affected brain development, known as the
      "Perspective Classification of Congenital Hydrocephalus (PCCH)." In this study
      the authors have used their classification system to analyze long-term follow-up
      results obtained in each clinicoembryological stage of fetal hydrocephalus.
      METHODS: Sixty-one fetuses with hydrocephalus were examined to predict postnatal
      outcome by using this newly developed classification. The authors' recently
      developed method of using heavily T2-weighted imaging with a superconducting
      magnet clearly delineated the cerebrospinal fluid (CSF) space and the malformed
      brain and spinal cord. Imaging was achieved in less than 1 second per slice and
      required no sedation of the fetus. The technique appears to be simple and good at
      delineating intrauterine anatomy. Hydrocephalus was diagnosed in two fetuses at
      PCCH embryological Stage I (8-21 gestational weeks), in 28 fetuses at Stage II
      (22-31 weeks), and in 31 fetuses at Stage III (32-40 weeks). Among these 61
      fetuses, clinicopathological typing showed that 19 had primary hydrocephalus
      (nine in Stage II and 10 in Stage III), 34 had dysgenetic hydrocephalus (two in
      Stage I, 16 in Stage II, and 16 in Stage III), and eight had secondary
      hydrocephalus (three in Stage II and five in Stage III). When the hydrocephalic
      state developed during PCCH Stage I or II, the prognosis was very poor, and only
      one of 18 fetuses with dysgenetic hydrocephalus and none of three fetuses with
      secondary hydrocephalus had an acceptable postnatal outcome. Even within the same
      category or subtype of fetal hydrocephalus, such as primary hydrocephalus in its
      simple form, or hydrocephalus with spina bifida aperta (myeloschisis), the
      postnatal outcomes differed depending on the time of onset of hydrocephalus. When
      the diagnosis of hydrocephalus was made during PCCH Stage II, the fetuses had a
      poorer postnatal outcome compared with those at Stage III (p < 0.05).
      CONCLUSIONS: It is emphasized that postnatal prognosis is not simply a function
      of the form of the diagnosis but is also dependent on the progression of
      hydrocephalus and the degree to which that process affects neuronal development.
      Early decompressive procedures, conventionally performed after but, hopefully,
      performed before birth, are indicated to obtain the optimal postnatal prognosis
      of fetuses with hydrocephalus diagnosed at PCCH Stage II.

PMID- 9525716
TI  - Survival and prognostic factors following radiation therapy and chemotherapy for
      ependymomas in children: a report of the Children's Cancer Group.
AB  - OBJECT: Ependymomas in children continue to generate controversy regarding their
      histological diagnosis and grading. optimal management, and possible prognostic
      factors. To increase our knowledge of these tumors the authors addressed these
      issues in a cohort of children with prospectively staged ependymomas treated with
      radiotherapy and chemotherapy. METHODS: Children between the ages of 2 and 17.3
      years harboring an intracranial ependymoma confirmed by a central review of the
      tumor's pathological characteristics were treated according to Children's Cancer
      Group Protocol 921 from 1986 to 1992. Treatment following surgery and
      postoperative tumor staging (including brain computerized tomography or magnetic
      resonance [MR] imaging, spinal MR imaging or myelography, and cerebrospinal fluid
      cytological investigation) included craniospinal irradiation with a local boost
      to the primary tumor and patient randomization to receive adjuvant chemotherapy
      with either 1) CCNU, vincristine, and prednisone, or 2) the eight-drugs-in-1-day
      regimen. Centralized review of the tumor pathological characteristics revealed 20
      ependymomas and 12 anaplastic ependymomas in the 32 children included in the
      study. Diagnoses made at the individual institutions included anaplastic
      (malignant) ependymoma (15 patients), ependymoma (four patients),
      ependymoblastoma (nine patients), ependymoastrocytoma (one patient), and
      primitive neuroectodermal tumor (three patients), which were discordant with the
      centralized review diagnosis in 22 of 32 cases. Only three of the 32 patients had
      metastatic disease (two with M and one with M3 stages). At surgery, 47% of tumors
      were estimated to be totally resected. Among the 14 of 17 patients who suffered a
      relapse and were evaluated for site of relapse, 10 (71%) had an isolated local
      relapse, three (21%) had concurrent local and metastatic relapse, and only one
      (7%) had an isolated metastatic relapse. Kaplan-Meier estimates of 5-year
      progression-free survival (PFS) and overall survival rates were 50 +/- 10% and 64
      +/- 9%, respectively. CONCLUSIONS: Predictors of PFS duration included an
      estimate of the extent of resection made at surgery (total compared with less
      than total, p = 0.0001) and the amount of residual tumor on postoperative imaging
      as verified by centralized radiological review (< or = 1.5 cm2 compared with >
      1.5 cm2, p < 0.0001). No other factors, including centrally reviewed tumor
      histopathological type, location, metastasis and tumor (M and T) stages, patient
      age, race, gender, or chemotherapy treatment regimen significantly correlated
      with PFS duration. The pattern of predominantly local relapse and the important
      influence of residual tumor or the extent of resection on PFS duration confirms a
      prevailing impression that local disease control is the major factor in the
      prediction of outcome of ependymoma. Survival rates were comparable with those
      reported by other investigators who have treated patients with similar doses of
      radiation and no chemotherapy.

PMID- 9525717
TI  - Increased hematocrit and decreased transfusion requirements in children given
      erythropoietin before undergoing craniofacial surgery.
AB  - OBJECT: This study was undertaken to determine the efficacy of preoperative
      erythropoietin administration in infants scheduled for craniofacial surgery and,
      in so doing, to minimize problems associated with blood transfusions. METHODS:
      Families were offered the option of having their children receive erythropoietin
      injections before undergoing craniofacial surgery. The children whose families
      accepted this option received daily iron and 300 U/kg erythropoietin three times
      per week for 3 weeks preoperatively. Weekly complete blood counts with
      reticulocyte counts were measured and transfusion requirements were noted. Blood
      transfusions were administered depending on the clinical condition of the child.
      A case-matched control population was also evaluated to compare initial
      hematocrit levels and transfusion requirements. Thirty patients in the
      erythropoietin treatment group and 30 control patients were evaluated. The dose
      of erythropoietin administered was shown to increase hematocrit levels from 35.4
      +/- 0.9% to 43.3 +/- 0.9% during the course of therapy. The resulting hematocrit
      levels in patients treated with erythropoietin at the time of surgery were higher
      compared with baseline hematocrit levels obtained in control patients at the time
      of surgery (34.2 +/- 0.5%). Transfusion requirements also differed: all control
      patients received transfusions, whereas 64% (19 of 30) of erythropoietin-treated
      patients received transfusions. CONCLUSIONS: The authors conclude that treatment
      with erythropoietin in otherwise healthy young children will increase hematocrit
      levels and modify transfusion requirements. Erythropoietin therapy for elective
      surgery in children of this age must be individualized according to the clinical
      situation, family and physician beliefs, and cost effectiveness, as evaluated at
      the individual center.

PMID- 9525718
TI  - Reversibility of functionally injured neurotransmitter systems with shunt
      placement in hydrocephalic rats: implications for intellectual impairment in
      hydrocephalus.
AB  - Intellectual impairment has been related to alteration of neuronal innervation in
      the following regions: cholinergic basal forebrain nuclei (Ch1-Ch6, learning and
      memory), dopaminergic ventral tegmental area (emotional control), and
      noradrenergic locus ceruleus (cognition). Recent studies have implicated neuronal
      injury in the pathogenesis of hydrocephalus. OBJECT: The authors used
      immunohistochemical techniques to investigate functional injury in these regions
      in animals with progressive hydrocephalus, following shunt placement for
      cerebrospinal fluid (CSF) drainage. METHODS: Hydrocephalus was induced in 20
      Wistar rats by intracisternal injection of 0.05 ml of 25% kaolin solution. Four
      control animals (Group 1) received the same volume of saline.
      Ventriculoperitoneal shunts were inserted in eight rats at 2 and 4 weeks after
      kaolin injection and the animals were killed at 8 weeks (Group 2). The other 12
      hydrocephalic animals were killed at 2, 4, and 8 weeks without undergoing shunt
      placement (Group 3). Immunoreactive (IR) neurons to choline acetyltransferase
      (ChAT) in Ch1-Ch6, tyrosine hydroxylase (TH) in the ventral tegmental area, and
      dopamine B-hydroxylase (DBH) in the locus ceruleus, as well as IR projection
      fibers in the terminal areas, were compared between groups. The number of ChAT-
      and TH-IR neurons in rats with and without shunt placement was counted for
      quantitative analysis. The number of ChAT-IR neurons was progressively reduced
      during the development of hydrocephalus in Ch1, Ch2, Ch3, and Ch4 (p < 0.05).
      Tyrosine-hydroxylase-immunoreactive neurons were also reduced in number, and
      demonstrated decreased projection fibers and terminals. Early shunting (at 2
      weeks) restored ChAT and TH immunoreactivity to control levels, but late shunting
      (at 4 weeks) did not (p < 0.05). The DBH-IR neurons in the locus ceruleus were
      remarkably compressed by the dilated fourth ventricle, and diminished
      immunoreactivity was observed in the terminal areas. Shunt placement for CSF also
      restored the immunoreactivity in this system. CONCLUSIONS: These findings
      indicate that a progressive functional injury occurs in the cholinergic,
      dopaminergic, and noradrenergic systems as a result of hydrocephalus. This may
      contribute to intellectual impairment and might be prevented by early treatment
      with shunt placement.

PMID- 9525719
TI  - Generator sites of early scalp potentials evoked from the three trigeminal
      branches.
AB  - OBJECT: The aim of this study was to seek evidence about the generators of the
      first three components of the scalp's early trigeminal evoked potentials (TEPs)
      obtained by stimulation of the supraorbital (SW1, SW2, and SW3), infraorbital
      (W1, W2, and W3) and mental (MW1, MW2, and MW3) nerves. METHODS: Simultaneous
      scalp and depth recordings were measured during surgical procedures in which
      thermorhizotomy and microvascular decompression were performed. CONCLUSIONS:
      Direct evidence was found that the origin of MW1 lies in the mandibular nerve at
      the foramen ovale, whereas the origin of W1 in the maxillary nerve at the foramen
      rotundum and the origin of SW1 in the ophthalmic nerve at the superior orbital
      fissure could only be inferred. The generators of SW2, W2, and MW2 were found to
      be on the nerve root at a distance of 10 mm from the pons. Calculations based on
      conduction velocity suggested that the generators of SW3, W3, and MW3 were inside
      the brainstem, at distances between 16 mm and 20 mm from the root entry zone.
      Recordings obtained in eight patients with discrete surgical lesions of the
      trigeminal pathway confirmed the sites of origin of the early components and
      further proved that only the fastest group of fibers is responsible for scalp
      responses.

PMID- 9525720
TI  - Preservation of ejaculatory function by reconstruction of the canine hypogastric
      nerve.
AB  - OBJECT: The hypogastric nerve (HGN) plays a crucial role in the primary functions
      of ejaculation: sperm transport through the vas deferens, secretion of prostatic
      fluid, and bladder neck closure. This study was undertaken to explore the
      possibility of restoring HGN function to the seminal tract and preserving its
      cross-innervation mechanism to the seminal tract after HGN-HGN reattachment.
      METHODS: Responses of the vas deferens/epididymis, prostate, and bladder neck to
      electrical stimulation of the lumbar splanchnic nerve (LSN) or the HGN and
      occurrence of antegrade ejaculation as a result of manual penile stimulation were
      examined in dogs that had undergone HGN-HGN reattachment. Eighteen months after
      the procedure had been performed bilaterally, 23 LSNs were electrically
      stimulated. In 17 LSNs this stimulation elicited elevation of vasal pressure (12
      nerves bilaterally); in 18 LNs, bladder neck pressure; and in 15 LSNs, prostate
      contraction. After retransection of the right HGN in the dogs that had undergone
      HGN-HGN reattachment, 11 right-sided LSNs were stimulated; in seven LSNs, the
      stimulation elicited elevation of vasal pressure (five bilaterally), in seven
      bladder neck pressure, and in six prostate contraction. Twelve left-sided LSNs
      were stimulated; in seven LSNs, the stimulation elicited elevation of vasal
      pressure (four bilaterally), in six bladder neck pressure, and in six prostate
      contracton. Each of the 12 HGN stimulations made proximal to the site that had
      been sutured in dogs that had HGN-HGN reattachment caused responses of the three
      organs specified above that were comparable to those in control dogs. Manual
      penile stimulation elicited antegrade ejaculation in all three dogs examined.
      CONCLUSIONS: The results of this study show that the function of the HGN in the
      seminal tract can be preserved after HGN-HGN reattachment and that restoration of
      its cross-innervation mechanism is possible.

PMID- 9525722
TI  - Microanatomy of the hypophyseal fossa boundaries.
AB  - OBJECT: The authors studied the heads of 17 adult cadavers and one fetus to
      clarify the anatomy of the sellar region, particularly the lateral boundaries of
      the hypophyseal fossa. METHODS: Vascular injections and microdissection or
      histological techniques were used in this study. The roof of the cavernous
      sinuses and diaphragma sellae were part of a single horizontal dural layer that
      joined the two anterior petroclinoid folds. Laterally, the direction of this
      layer changed; it became the lateral wall of the cavernous sinus and joined the
      dura mater of the middle cerebral fossa. On the midline, this layer ballooned
      toward the sella through the diaphragmatic foramina, created a dural bag
      containing the hypophysis, and attached to the inferior aspect of the diaphragma
      sellae. As a consequence, no straight sagittal dural wall existed between the
      pituitary gland and cavernous sinus; the lateral border of the hypophyseal fossa
      was part of this anteroposterior and superoinferior convex bag. The authors
      stress the importance of the venous elements of the region and discuss the
      structure of the cavernous and coronary sinuses. CONCLUSIONS: Invasion of the
      cavernous sinus makes surgery more risky and difficult and may necessitate
      modification of the surgical treatment plan. The preoperative diagnosis of
      cavernous sinus invasion is thus of great interest, but the possibility of normal
      lateral expansions of the pituitary gland must be kept in mind. A lateral
      expansion of this gland into the cavernous sinus was encountered in 29% of the
      specimens, and an adenoma that developed in such an expansion could easily mimic
      cavernous sinus invasion.

PMID- 9525721
TI  - Distribution and stability of antisense phosphorothioate oligonucleotides in
      rodent brain following direct intraparenchymal controlled-rate infusion.
AB  - OBJECT: High-flow microinfusion is a novel technique for delivery of compounds
      directly into brain parenchyma, bypassing the blood-brain barrier. The
      feasibility of this technique has been demonstrated with low-molecular-weight
      compounds, macromolecular dyes, and proteins. Delivery of antisense
      oligonucleotides into brain parenchyma represents an additional potential
      application of this technique not previously described. In this report the
      authors sought to examine the distribution and disposition of phosphorothioate
      oligodeoxynucleotide (PS-ODN) for this reason. METHODS: An 18-mer 35S-PS-ODN (Mr
      approximately 6000) was infused over 1 hour into the caudate putamen of Fischer
      344 rats. At 1, 6, 12, 24, and 48 hours after beginning the infusion, the brains
      were extracted and analyzed using quantitative autoradiographic techniques.
      Cerebrospinal fluid (CSF) was also aspirated from the cisterna magna and was
      analyzed to determine the radioactivity and stability of the 35S-PS-ODN. At 1
      hour, the infused ODN was uniformly distributed in brain tissue, with a maximum
      average concentration of 4806.5 +/- 210.5 nCi/g. This represents a tissue
      concentration of 19.2 +/- 0.84 microM. Extensive spread into surrounding
      parenchyma was observed over the ensuing 47 hours. The 35S-PS-ODN radioactivity
      peaked in the CSF at the end of the 1-hour infusion, containing 1% (50 +/- 20
      nCi) of the infused radioactivity. Activity then decayed exponentially over 11
      hours, but stabilized at a lower CSF content of 0.2% (1 +/- 0.1 nCi) thereafter.
      The volume of distribution was 105 +/- 7.9 mm3 at 1 hour, representing a volume
      of distribution/volume of infusion ratio of 5.2. The volume of distribution
      increased to 443 +/- 62.3 mm3 at the end of 48 hours, whereas the average minimum
      tissue concentration decreased from 15.2 microM to 3.2 microM. Undegraded 18-mer
      was observed throughout the 48-hour period by means of 20% polyacrylamide/7 M
      urea gel electrophoresis. The animals tolerated the infusion without evidence of
      toxicity and minimal structural changes in tissue were observed on histological
      investigation. CONCLUSIONS: The authors found that PS-ODNs can be safely
      delivered in high concentrations to wide areas of rat brain by using high-flow
      microinfusion and are stable even after 48 hours in situ.

PMID- 9525723
TI  - Prolonged survival in a patient with sinonasal teratocarcinosarcoma with cranial
      extension. Case report.
AB  - Sinonasal teratocarcinosarcoma is a rare malignant neoplasm characterized by the
      combined histological features of carcinosarcoma and teratoma. The primary
      symptoms of this tumor are usually nasal obstruction and epistaxis, and a nasal
      cavity mass is the most common clinical finding. The authors describe an
      exceptionally rare case in which the patient presented with massive intracranial
      extension and exhibited confusion as an initial symptom. He subsequently
      underwent combined radical surgery and radiation therapy and has remained free of
      disease for 31 months. The surgical approach to the lesion, histological
      features, and clinical course are detailed.

PMID- 9525724
TI  - Diffuse craniospinal seeding from a benign fourth ventricle choroid plexus
      papilloma. Case report.
AB  - Choroid plexus papillomas can metastasize to the subarachnoid space, but
      extensive metastasis has only been reported when the tumors are malignant. The
      authors report a case of diffuse, extensive metastasis to the craniospinal
      leptomeninges from a benign fourth ventricular choroid plexus papilloma in an
      adult. This 19-year-old woman presented with a 2-year history of headache,
      blurred vision, diplopia, and ataxia. Magnetic resonance imaging of the brain and
      spinal cord revealed obstructive hydrocephalus caused by a 4-cm, partially
      calcified, inhomogeneously enhancing tumor of the fourth ventricle that was
      displacing the pons, medulla oblongata, and cerebellum. Innumerable cystic
      lesions of varying size were also seen in the cranial and spinal leptomeninges.
      Histological examination of the resected fourth ventricular tumor and of a few of
      the leptomeningeal lesions revealed a benign choroid plexus papilloma and
      leptomeningeal choroid plexus cysts. This singular case of diffuse and extensive
      metastasis to the craniospinal leptomeninges from a histologically benign fourth
      ventricular papilloma adds to the available information about the biological
      potential of these tumors and expands the differential diagnosis of posterior
      fossa lesions with subarachnoid metastasis.

PMID- 9525725
TI  - Brain metastasis from germinal tumors of the testis. Case report.
AB  - Brain metastasis in patients with disseminated nonseminomatous germ cell tumor
      (NSGCT) has been considered to occur rarely. The authors present the case of a 43
      year-old man with an enlarged left testicle, a palpable inguinal tumor, multiple
      lung tumors, and a large cerebellar tumor. In separate operations, performed 1
      month apart, the large cerebellar tumor and the testicular tumor were excised.
      Elements of teratocarcinoma, embryonal carcinoma, and choriocarcinoma were
      present in both the brain and testicular tumors. After chemotherapy in which
      bleomycin, etoposide, and cisplatin were used, the lung tumors and also the
      surrounding metastasis disappeared; the patient now leads a useful life and
      remains free from cancer in all organs. The authors suggest that surgical removal
      of tumor before initiating radiotherapy and chemotherapy for large brain
      metastasis from NSGCT will produce better results than using the nonsurgical
      treatments alone.

PMID- 9525726
TI  - Intradural retroclival chordoma without bone involvement: no tumor regrowth 5
      years after operation. Case report.
AB  - Chordomas are most commonly located in the extradural region. A 56-year-old man
      presented with a large chondroid chordoma located totally within the intradural
      retroclival region. The tumor was resected via the petrosal approach. Five years
      after subtotal removal, the residual tumor showed no sign of regrowth despite the
      fact that radiation therapy had not been used. The patient was free of symptoms
      except for moderate, conductive hearing loss in his right ear. The position of
      the intradural tumor could be preoperatively diagnosed by neuroimaging and, thus,
      the petrosal approach was selected. Primary intradural extraosseous chordomas are
      very rare and difficult to differentiate from ecchordoses physaliphorae on the
      basis of histological and radiological features; however, MIB-1 staining may be
      useful.

PMID- 9525728
TI  - Unusual occipitoatlantal fracture dissociation with no neurological impairment.
      Case report.
AB  - The authors describe an unusual case of a complex traumatic fracture-dissociation
      injury of the craniovertebral junction, which the patient survived with no
      neurological damage. This case featured the rare combination of an avulsion of
      both the right occipital condyle and clivus and a fracture of the left lateral
      mass of the atlas. Because of the craniocervical ligament injury and the slight
      anterior occipitoatlantal dislocation, the lesion was considered to be unstable
      and was treated successfully with a cervical collar. The authors emphasize that
      thin-slice computerized tomography scanning with multiplanar reconstructions is
      essential to visualize these fractures, whereas magnetic resonance imaging is
      useful to assess soft tissues.

PMID- 9525727
TI  - Acute quadriplegia with delayed onset and rapid recovery. Case report.
AB  - The authors describe a patient with severe head injury and sepsis who became
      acutely quadriplegic 3 days postinjury because of a critical illness
      polyneuropathy (CIP) and critical illness myopathy (CIM), which resolved rapidly
      after treatment of the underlying infection. In only 3 days the patient developed
      septic shock together with flaccid quadriplegia and absent deep tendon reflexes
      with no clinical or radiological evidence of central nervous system
      deterioration. Neurophysiological studies showed an acute axonal sensorimotor
      polyneuropathy, whereas the clinical course strongly suggested a concurrent
      myopathy. A severe Staphylococcus epidermidis infection accompanied by bacteremia
      was treated and the patient recovered fully within a few days. Although the case
      described here is unique because of its very early onset and rapid resolution,
      CIP and CIM are frequent complications of sepsis and multiple organ failure. The
      authors suggest that severely head injured patients with sepsis should be
      evaluated for CIP and CIM when presenting with unexplained muscle weakness or
      paralysis.

PMID- 9525729
TI  - Superimposed holographic image-guided neurosurgery. Technical note.
AB  - Computerized tomography scanning-derived narrow band reflection holograms of
      patients undergoing craniofacial procedures were created to evaluate the
      applicability of superimposing these three-dimensional images (3-D) on the
      operative field during neurological surgery. These sterilized radiological
      holograms were positioned over the surgical site by using bone sutures as
      registration points between the skull and the 3-D image to serve as a visual
      template between the patient and surgeon. Surgeries were then performed with the
      surgeon looking through the radiological hologram at the patient. Holograms were
      accurate to within 2 mm (plus or minus) of the actual calvarial anatomy. The use
      of the holographic image as a visual guide during surgery eliminated
      intraoperative guesswork or free-handed contouring. To the author's knowledge,
      this is the first report of the superimposed holographic image used in situ
      during surgery.

PMID- 9525730
TI  - Development of neurosurgery in Greece: past, present, and future.
AB  - In this study the authors examine the historical tradition as well as current
      features of neurosurgery in Greece and compare the available data with
      international standards. In particular, they describe the organizational
      structure of neurosurgery with reference to manpower, unit distribution,
      training, and qualification. They discuss problems such as overproduction of
      neurosurgeons and the poor control of training and qualification procedures in
      the neurosurgical profession. The findings are examined in a critical way and
      solutions are proposed that could improve the present situation.

PMID- 9525731
TI  - Smoking and vasospasm.

PMID- 9525732
TI  - Pituitary adenomas.

PMID- 9525733
TI  - Error in anatomical detail?

PMID- 9525734
TI  - Langerhans' cell histiocytosis.

PMID- 9525735
TI  - Decompressive laminectomy for spinal stenosis.

PMID- 9525736
TI  - The retinoblastoma protein is essential for cyclin A repression in quiescent
      cells.
AB  - Cyclin A is a positive regulatory component of kinases required for the
      progression through S phase and for the transition between the G2 and M phases of
      the cell division cycle. Previous studies have demonstrated that the promoter of
      its gene is under transcriptional repression in quiescent cells. Whereas the DNA
      sequences mediating this effect have been clearly delineated, the nature of the
      proteins acting in trans is still debated. Indirect observations suggest the
      involvement of proteins related to the retinoblastoma tumor suppressor protein
      (pRb). However, the precise role of these proteins has been difficult to assess,
      since most experiments designed to analyse their function have been carried out
      in transformed cell lines. Nevertheless, a current model has emerged whereby the
      role of the p130 protein would be restricted to resting and early G1 cells and
      p107, absent in quiescent cells, would be involved later in the control of the
      G1/S transition, whilst pRb would be effective throughout the cell cycle. We show
      here that cyclin A transcriptional inhibition is relieved in primary fibroblasts
      from pRb(-/-) embryos and not in fibroblasts from p13O(-/-), p107(-/-) or even
      p130(-/-)/p107(-/-) double mutant embryos. This suggests a unique role for pRb in
      controlling the extinction of specific genes in G0, providing thus the first
      example of non-overlapping functions achieved by the different pocket proteins.

PMID- 9525737
TI  - Bcl-2-independent Bcr-Abl-mediated resistance to apoptosis: protection is
      correlated with up regulation of Bcl-xL.
AB  - Bcr - Abl is the molecule responsible for both the transformation phenotype and
      the resistance to chemotherapeutic drugs found in chronic myelogenous leukemia
      (CML) cells. Wild-type HL-60, a transformed pro-myelocytic cell line, is very
      susceptible to apoptosis-inducing agents. We show here that expression of Bcr -
      Abl in HL-60 cells rendered them extremely resistant to apoptosis induced by a
      wide variety of agents. The anti-apoptotic effect of Bcr - Abl was found to be
      independent of the phase of the cell cycle. Treatment with antisense
      oligonucleotides directed to bcr decreased the expression of the ectopic bcr -
      abl and restored susceptibility to apoptosis. Double mutations affecting the
      autophosphorylation site and the phosphotyrosine-binding motif (FLVRES) have been
      previously shown to impair the transforming activity of Bcr - Abl in fibroblasts
      and hematopoietic cells, however HL-60 cells expressing this double mutant
      molecule exhibited the same level of resistance to apoptosis as those expressing
      the wild-type Bcr - Abl. Interestingly, wild type and mutant Bcr - Abl induced in
      HL-60 cells a dramatic down regulation of Bcl-2 and increased the levels of Bcl
      xL. The level of Bax did not change in response to the presence of Bcr - Abl.
      Antisense oligonucleotides targeted to bcl-x downregulated the expression of Bcl
      x, and increased the susceptibility of HL-60. Bcr - Abl cells to staurosporine.
      Importantly, HL-60 cells overexpressing Bcl-xL showed higher expression of Bcl-xL
      but lower resistance to apoptosis when compared to HL-60. Bcr - Abl cells. The
      results described here show that Bcr - Abl is a powerful mammalian anti-apoptotic
      molecule and can act independently of Bcl-2. Bcl-xL, however, seems to
      participate in part in Bcr - Abl-mediated resistance to apoptosis in HL-60 cells.

PMID- 9525738
TI  - Tumor cell growth inhibition by caveolin re-expression in human breast cancer
      cells.
AB  - Cancer development is a multistage process that results from the step-wise
      acquisition of somatic alterations in diverse genes. Recent studies indicate that
      caveolin-1 expression correlates with the level of oncogenic transformation in
      NIH3T3 cells, suggesting that caveolin in caveolae may regulate normal cell
      proliferation. In order to better understand potential functions of caveolin-1 in
      cancer development, we have studied expression levels of caveolin-1 in human
      breast cancer cells, and have found that caveolin expression is significantly
      reduced in human breast cancer cells compared with their normal mammary
      epithelial counterparts. When the caveolin cDNA linked to the CMV promoter is
      transfected into human mammary cancer cells having no detectable endogenous
      caveolin, overexpression of caveolin-1 resulted in substantial growth inhibition,
      as seen by the 50% decrease in growth rate and by approximately 15-fold reduction
      in colony formation in soft agar. In addition, characterization of caveolin-1
      expression during cell cycle progression indicates that expression of alpha
      caveolin-1 is regulated during cell cycle. Furthermore p53-deficient cells showed
      a loss in caveolin expression. In summary, the overall expression patterns, its
      ability to inhibit tumor growth in culture, its regulation during the cell cycle,
      and the loss of expression in p53-deficient cells all are consistent with an
      important growth regulating function for caveolin-1 in normal human mammary
      cells, that needs to be repressed in oncogenic transformation and tumor cell
      growth.

PMID- 9525739
TI  - Bcl-X is the major pleiotropic anti-apoptotic gene activated by retroviral
      insertion mutagenesis in an IL-3 dependent bone marrow derived cell line.
AB  - In order to identify genes capable of inhibiting apoptosis induced by different
      pathways, without inducing proliferation we have performed retroviral insertion
      mutagenesis in the IL-3 dependent bone marrow derived Baf-3 cell line. Out of 200
      mutants obtained in three separate mutagenesis experiments, four mutants were
      resistant to multiple apoptosis inducing pathways (including growth factor
      starvation, staurosporine, etoposide and cyclosporin A) and did not proliferate
      in the absence of IL-3. These four mutants overexpress the bcl-X gene following a
      retroviral insertion 5' of the translation initiation site. These results
      indicate that the bcl-X gene is a major pleiotropic anti-apoptotic gene in Baf-3
      cells. They also suggest that the Bcl-2 family of genes might be the only one
      capable of inhibiting apoptosis induced by multiple pathways without inducing
      cell proliferation.

PMID- 9525740
TI  - The recurrent translocation t(5;8)(p13;q12) in pleomorphic adenomas results in
      upregulation of PLAG1 gene expression under control of the LIFR promoter.
AB  - We have previously shown that the PLAG1 gene on chromosome 8q12 is consistently
      rearranged in pleomorphic adenomas of the salivary glands with t(3;8)(p21;q12)
      translocations. The t(3;8) results in promoter swapping between the PLAG1 gene,
      which encodes a novel zinc finger protein, and the constitutively expressed gene
      for beta-catenin (CTNNB1), a protein with roles in cell-cell adhesion and the
      WG/WNT signalling pathway. In order to assess the importance of other
      translocation partner genes of PLAG1, and their possible relationship to CTNNB1,
      we have characterized a second recurrent translocation, i.e. the t(5;8)(p13;q12).
      This translocation leads to ectopic expression of a chimeric transcript
      consisting of sequences from the ubiquitously expressed gene for the leukemia
      inhibitory factor receptor (LIFR) and PLAG1. As for the t(3;8), the fusions
      occurred in the 5'-noncoding regions of both genes, exchanging regulatory control
      elements while preserving the coding sequences. The results of the current as
      well as previous studies indicate that ectopic expression of PLAG1 under the
      control of promoters of distinct translocation partner genes is a general
      pathogenetic mechanism for pleomorphic adenomas with 8q12 aberrations.

PMID- 9525741
TI  - Ha-ras and N-ras regulate MAPK activity by distinct mechanisms in vivo.
AB  - The Ras GTPases function as molecular switches, regulating a multiplicity of
      biological events. However the contribution, if any, of a specific c-Ras isoform
      (Ha-, N-, or Ki-ras A or B) in the regulation of a given biological or
      biochemical process, is unknown. Murine C3H1OT1/2 fibroblasts transformed with
      activated (G12V)Ha-ras or (Q61K)N-ras proliferate in serum-free media and have
      constitutive MAPK activity. The growth factor antagonist, suramin, inhibited the
      serum-independent proliferation of Ha-ras transformed fibroblasts, but not the
      serum-independent proliferation of N-ras transformed cells. The inhibition of
      cell proliferation was concomitant with the abrogation of the constitutive MAPK
      activity in the Ha-ras transformed fibroblasts. Analysis of the Ras-signalling
      complexes in immunoprecipitates from Ha-ras transformed cells revealed that Raf-1
      co-immunoprecipitated with endogenous c-N-ras but not (G12V)Ha-ras. Pretreatment
      with suramin resulted in the loss of Raf-1 from c-N-ras immunoprecipitates. A c-N
      ras antisense oligonucleotide, which down-regulated c-N-ras protein levels,
      abrogated the constitutive MAPK activity and serum-independent proliferation of
      (G12V)Ha-ras transformed cells. The data suggest that Raf-1 has a higher affinity
      for N-ras then Ha-ras in vivo, and c-N-ras function is required for the serum
      independent proliferation of Ha-ras transformed cells.

PMID- 9525742
TI  - A transforming p53 mutant, which binds DNA, transactivates and induces apoptosis
      reveals a nuclear:cytoplasmic shuttling defect.
AB  - The DG75 Burkitt lymphoma-derived human B cell line is heterozygous for p53,
      carrying wild type (WT) and mutant (Arg283His) alleles. The cells constitutively
      express high levels of both p53 proteins and also Mdm2. Arg283His transactivates
      the p21Waf1, Mdm2, bax, cyclin G and IGF-BP3 promoters in transient transfection
      assays equally as well as, if not better than WT p53. It also suppresses the
      outgrowth of SAOS-2 cells and specifically binds DNA like wild type protein.
      However, in primary rodent fibroblasts Arg283His fails to suppress transformation
      by HPV16-E7 and (Ha-)ras and even has modest transforming activity when
      transfected alone with (Ha-)ras. When Arg283His is transiently transfected into
      SAOS-2 cells it efficiently induces apoptosis, so - unlike mutants such as
      Arg175Pro - its behaviour in transformation assays does not clearly correlate
      with loss of the apoptosis function. Immunofluorescence staining of both REF
      transformants and transiently transfected SAOS-2 revealed that this unusual
      mutant becomes excluded from the nucleus and produces striking cytoplasmic
      fluorescence. The best correlation with transformation, therefore, appears to be
      the lack of nuclear retention of Arg283His. Since this mutation does not map to
      any known nuclear localization signal and its presence seems to result in
      aberrant exclusion from the nucleus, then it may prove very useful in exploring
      mechanisms involved in the nuclear:cytoplasmic shuttling of p53.

PMID- 9525744
TI  - TGF-beta1 actions on FRTL-5 cells provide a model for the physiological
      regulation of thyroid growth.
AB  - Little is known about the TGF-beta1 mechanism that promotes thyroid cell growth
      arrest. We assessed TGF-beta1 effects on Fisher rat thyroid cell line (FRTL-5).
      This allowed us to study TGF-beta1 action on thyroid cells in various
      physiological situations such as actively proliferating cells, resting cells
      stimulated to proliferate by the action of various mitogens, and resting cells.
      TGF-beta1 arrested proliferating FRTL-5 cells, increasing c-myc mRNA levels and
      reducing p27-free cyclin D1 protein levels, without affecting either the cellular
      content of p27 or the cyclin D1-p27 complexes. Moreover, TGF-beta1 treatment
      reduced the activity of cyclin E-CDK2 complexes and, consequently, pRB was found
      to be hypophosphorylated. TGF-beta1 prevented resting cells to enter in the cell
      cycle when stimulated with growing medium (newborn calf serum plus a mixture of
      five hormones) but not when TSH (thyroid stimulating hormone) plus IGF-1 (Insulin
      like growth factor I) were used as mitogens. Both stimuli increased the levels of
      cyclins D1, D3 and E but TGF-beta1 had a greater effect in decreasing these
      cyclin levels in growing-medium stimulated cells than in TSH + IGF-1. This
      suggests that for FRTL-5 cells, the content of these cyclins must exceed a
      threshold to progress through the cell cycle. TGF-beta1 induced apoptosis in
      quiescent cells, accompanied by a reduction in p27 protein levels and an increase
      in c-myc expression. Interestingly, TGF-beta1-induced variations in prothymosin
      alpha and c-myc mRNA levels were not correlated. TGF-beta1 always promoted an
      increase of p15 mRNA levels. In summary, our results point to the fact that TGF
      beta1 could play a physiological role in the control of thyroid growth through
      the modification of cell cycle regulatory proteins.

PMID- 9525743
TI  - Suppression of invasive properties of colon cancer cells by a metastasis
      suppressor KAI1 gene.
AB  - KAI1 is a potential metastatic suppressor gene for prostate cancer. We found by
      Northern blot analysis that six of ten (60%) gastric and colon cancer cell lines
      exhibited undetectable or very low expression level of KAI1 mRNA. The effects of
      KAI1 on the adhesion, motility and invasiveness of colon cancer cells was
      therefore investigated by using two kinds of stable transfectants, i.e.,
      antisense transfectants of BM314 cells whose KAI1 mRNA expression was suppressed
      by transfer of antisense KAI1 cDNA and sense transfectants of DLD-1 cells with
      the enhanced KAI1 mRNA by sense cDNA transfer. The following results were
      obtained: (1) KAI1 gene expression had no significant effect on in vitro cell
      growth rate of colon cancer BM314 and DLD-1 cells; (2) Cell aggregation assay
      showed that KAI1 enhanced the Ca++-independent aggregatability of those colon
      cancer cells; (3) It was revealed by cell motility and invasion assays that KAI1
      suppressed both the motility and in vitro invasiveness of those cells and (4)
      Furthermore, both the binding to fibronectin and the migration on fibronectin
      coated plates of those cells were inhibited by KAI1 expression. These suggest
      that reduced KAI1 gene expression may contribute to the invasiveness and
      metastatic ability of colon cancer cells.

PMID- 9525745
TI  - Both farnesyltransferase and geranylgeranyltransferase I inhibitors are required
      for inhibition of oncogenic K-Ras prenylation but each alone is sufficient to
      suppress human tumor growth in nude mouse xenografts.
AB  - The ability of Ras oncoproteins to cause malignant transformation requires their
      post-translational modifications by prenyl groups. Because K-Ras can be both
      farnesylated and geranylgeranylated it is not known whether both
      farnesyltransferase and geranylgeranyltransferase I inhibitors are required for
      suppressing human tumor growth in whole animals. In this paper we report that
      oncogenic Ras processing, MAP kinase activation and growth in nude mice are
      inhibited by the farnesyltransferase inhibitor FTI-276 in H- and N-Ras
      transformed NIH3T3 cells; whereas in KB-Ras transformed NIH3T3 cells both FTI-276
      and the geranylgeranyltransferase I inhibitor GGTI-297 are required for
      inhibition. Furthermore, human lung A-549 and Calu-1 carcinoma cell lines were
      found to co-express H-, N- and K-Ras. In Calu-1 cells, the processing of H- and N
      Ras is inhibited greatly by FTI-276 but only partially by GGTI-297 whereas K-Ras
      processing inhibition requires both FTI-276 and GGTI-297. In contrast, in A-549
      cells the processing of H- and N-Ras is inhibited only by FTI-276 and K-Ras
      processing is resistant to co-treatment with FTI-276 and GGTI-297. Yet, the
      growth in nude mice of A-549 and Calu-1 xenografts, both of which express K-Ras
      mutations, is inhibited by FTI-276 (80% inhibition) and GGTI-297 (60%).
      Furthermore, FTI-276 inhibits tumor growth of NIH3T3 cells transformed by a form
      of oncogenic H-Ras that is exclusively geranylgeranylated and whose processing is
      resistant to this inhibitor. Taken together, the results demonstrate that both
      FTase and GGTase I inhibitors are required for inhibition of K-Ras processing but
      that each alone is sufficient to suppress human tumor growth in nude mice.

PMID- 9525746
TI  - Distinct rat proteins can recognize CCAAT-homologous sequences of the
      metallothionein promoter and trans-activate this promoter.
AB  - We have previously purified and characterized a rat liver protein C'BP-1 that is
      either identical or closely related to C/EBPdelta (Aniskovitch and Jacob, 1997).
      The mouse metallothionein-I (MT-I) promoter contains two C'BP-1 binding sites,
      one of which includes the MRE-c' region (-135 to -110). The C'BP-1 binding
      activity was detected by EMSA as a major activity for MRE-c' in nonproliferating
      adult liver cells but not in rat hepatoma cells. In this study, we purified and
      characterized a factor, C'BP-2, which had a dominant binding activity for MRE-c'
      in Morris hepatoma 3924A, a poorly differentiated, fast-growing tissue. C'BP-2 is
      a 28 kDa protein which exists in solution as a monomer. As observed for C'BP-1,
      affinity-purified C'BP-2 stimulated transcription from the mMT-I gene promoter.
      DNase I footprinting revealed two C'BP-2 binding sites in the regions that
      overlap with the CCAAT homologies of the C'BP-1 binding sites on the mMT-I
      promoter. C'BP-2 made essential contacts with the CCAAT homology and in the
      region upstream of this sequence. Competition electrophoretic mobility shift
      assay and methylation interference analysis revealed that C'BP-2 is a protein
      closely related, but not identical, to CP2. These data suggest that C'BP-1 and
      C'BP-2 may play a role in hepatocyte proliferation and/or differentiation.

PMID- 9525747
TI  - Downregulation of human FGF8 activity by antisense constructs in murine
      fibroblastic and human prostatic carcinoma cell systems.
AB  - Previously, we described cloning of three alternatively spliced mRNA forms of
      human FGF8, a, b, and e, of which the b form is the major expressed species in
      both normal and tumor prostatic epithelial cells. In this report, we describe
      construction and overexpression of sense and antisense sequences of either the
      full length FGF8b coding region (215-amino acids or 215aa), 103aa N-terminal part
      or a smaller N-terminal region (34aa), each including the 23aa putative signal
      peptide domain, via a retrovirus system. While the morphologic transforming
      activities of the sense 215aa and 103aa constructs were similar in NIH3T3 cells,
      103aa displayed reduced soft agar clonogenic activity. The 34aa construct was
      practically inert in these assays, although its expression could mimic the
      ability of 215aa or 103aa in conferring cell growth under reduced serum
      condition. Overexpression of any of the three constructs in antisense
      orientation, however, was similarly effective in reversing the morphology and
      anchorage-independent growth property of FGF8b-transfected NIH3T3 cells. The
      expression of the antisense 215aa construct significantly reduced the growth rate
      of the human prostatic carcinoma DU145 cells and inhibited their soft agar
      clonogenic activity and in vivo tumorigenicity in nude mice. Taken together,
      these results identify N-terminal portions of FGF8 protein isoform for having the
      domains necessary for one or more of the biologic effects examined, and suggest
      that low levels of FGF8 expressed in prostatic epithelial cells may contribute
      significantly to their growth and tumorigenic properties.

PMID- 9525748
TI  - Rapid activation of JNK1 in UV-B irradiated epidermal keratinocytes.
AB  - Jun N-terminal kinase (JNK1) is a member of a family of stress-activated protein
      kinases which are activated by many forms of stress including UV radiation,
      resulting in the phosphorylation of c-Jun, ATF-2, Elk-1 and p53. As UV-B
      radiation is mainly responsible for ultraviolet (UV)-induced skin cancers, we
      chose to elucidate JNK1 activation in keratinocytes which represent a UV-relevant
      cell system. We have demonstrated rapid activation of JNK1 in a keratinocyte cell
      line, C50, in response to multiple doses of UV-B irradiation. JNK1 activation
      occurred within 1 min, peaked by 10 min and returned to near basal levels within
      2 h following the UV-B treatments. Our data provide the first evidence to show
      that keratinocytes do respond to multiple doses of the physiologically relevant
      UV-B radiation through rapid activation of the JNK1 pathway.

PMID- 9525749
TI  - p53-dependent induction of WAF1 by cold shock in human glioblastoma cells.
AB  - Induction of WAF1 expression was investigated in human glioblastoma cell lines
      differing in p53 gene statuses after cold shock treatment. Accumulation of both
      wild-type (wt) and mutant p53 (mp53) was induced by cold shock at 4 degrees C for
      60 min, however, WAF1 accumulation was induced by cold shock in A-172 cells
      carrying the wtp53 but not in T98G cells carrying the mp53. Inactivation of wtp53
      by a dominant negative p53 mutant (p53Trp248) abolished cold shock-induced WAF1
      expression in A-172 transfectant cells. Furthermore, no WAF1 expression was
      induced by cold shock in p53-deficient human osteosarcoma Saos-2 cells. Northern
      blot analysis showed that the WAF1 but not p53 gene was activated by cold shock
      only in A-172 cells. These findings suggest that WAF1 expression is cold shock
      inducible in human glioblastoma cells, and that this induction may be due to
      signal transduction mediated by p53 in response to non-genotoxic stress, cold
      shock.

PMID- 9525750
TI  - Air-filled ultrasound contrast agents do not damage the cerebral microvasculature
      or brain tissue in rats.
AB  - RATIONALE AND OBJECTIVES: Air microemboli may damage the cerebral
      microvasculature. The aim of this study was to evaluate the safety of ultrasound
      contrast agents composed of air microspheres with regard to cerebral damage when
      administered into the arterial system (ie, when not filtered by the capillary
      system of the lungs). METHODS: Three experimental methods were used in 75 rats
      after injection of either Albunex, Echovist, or Levovist into the left heart
      ventricle. The alkaline phosphatase (ALP) method to demonstrate small segmental
      brain capillary and arteriolar dilatations (SCADs), intravenous injections of
      Evans blue and fluorescence microscopy to detect increased vascular permeability
      (blood-brain barrier damage), and histologic examination of the brain to detect
      microinfarction. Intracardiac injections of saline, air, and corn oil were used
      as controls. RESULTS: Brain microinfarcts and SCADs formation of the brain
      microvasculature occurred only after control injections with corn oil. None of
      the brains from animals that received ultrasound contrast agent showed gross
      discoloration, as an indication of increased vascular permeability, with the
      Evans blue/fluorescence microscopy method. Definite leakage of Evans blue
      occurred only after large doses (150 microL) of air. CONCLUSIONS: This study
      indicates that ultrasound contrast media composed of air microspheres do not
      cause lesions of the brain microvasculature or parenchyma.

PMID- 9525751
TI  - Biphasic spiral computed tomography versus digital subtraction angiography for
      evaluation of arterial thrombosis after orthotopic liver transplantation.
AB  - RATIONALE AND OBJECTIVES: The authors characterize the spiral computed
      tomographic (CT) findings in patients with hepatic arterial thrombosis after
      orthotopic liver transplantation (OLT). METHODS: In nine with and 15 patients
      without hepatic artery thrombosis (HAT) after OLT, unenhanced and contrast
      enhanced biphasic spiral CT was performed during arterial and venous phases, and
      evaluated by consensus of two blinded readers. Evaluation included signs of
      parenchymal and vascular changes in the liver. Findings subsequently were
      correlated with those of digital subtraction angiography (DSA). RESULTS: Among
      all patients, eight had complete occlusion of the proximal hepatic artery and one
      patient had partial thrombosis, as revealed by conventional DSA. Characteristic
      CT findings of HAT included irregularly shaped confluent hypoattenuating liver
      areas (n = 8), seen both before and after administration of contrast material.
      Necrotic lesions and changes consistent with ischemic type of biliary lesion were
      documented in six patients. Biphasic CT allowed detection of HAT in eight
      patients. Because of inadequate contrast enhancement during the arterial phase,
      thrombosed intrahepatic arteries were not adequately diagnosed in one patient.
      Overall CT sensitivity to detect HAT was 89%, specificity was 100%. CONCLUSIONS:
      Characteristic biphasic spiral CT findings in hepatic artery thrombosis
      contribute to early detection of arterial thrombosis after OLT and are helpful
      for planning more invasive diagnostic approaches.

PMID- 9525752
TI  - Transition of the craniocaudal velocity of the spinal cord: from cervical segment
      to lumbar enlargement.
AB  - RATIONALE AND OBJECTIVES: The authors investigate the craniocaudal velocity of
      the spinal cord over its full length by using magnetic resonance imaging.
      METHODS: A spin-echo pulse sequence with velocity encoding gradients was used to
      examine five normal volunteers. Oblique-axial phase images at nine levels, from
      cervical spinal cord to lumbar enlargement, were obtained with prospective
      electrocardiogram gating. Time-velocity curves were then generated for these
      levels. RESULTS: Every part of the spinal cord moves first caudally after the R
      wave of the electrocardiogram, then cranially. When compared with the cranial
      levels, peak velocity tend to occur later and their values tend to be smaller at
      the more caudal levels. CONCLUSIONS: Craniocaudal velocity is transmitted from
      cervical segment to lumbar enlargement.

PMID- 9525753
TI  - Assessment of vascularity in reactive lymph nodes by means of D-galactose
      contrast-enhanced Doppler sonography.
AB  - RATIONALE AND OBJECTIVES: A prospective study in signal-enhanced Doppler
      sonography of lymph nodes that were assumed pretherapeutically to be benign was
      performed to investigate characteristic sonomorphologic features and vascularity
      of reactively enlarged lymph nodes. METHODS: Thirty-four patients with enlarged
      superficial lymph nodes of the neck were examined first by B-scan sonography then
      by Doppler sonography before and after administration of an ultrasound signal
      enhancing agent. In B-scan sonography, lymph nodes were classified into three
      groups according to their sonomorphologic features: (1) homogeneous parenchyma,
      (2) a centrally located echogenoic line, and (3) a echogenoic "hilus reflex." In
      conventional and contrast-enhanced Doppler sonography, peak flow rate,
      pulsatility index, and resistive index were assessed. Sonomorphologic criteria
      were compared with histologic findings. RESULTS: Reactively enlarged lymph nodes
      showed characteristic sonomorphologic patterns correlating to their histologic
      features. Echogenicity of the hilus corresponded to fibrosis (centrally located
      echogenoic line in 13 nodes; 38.2%) or fatty involution of the hili (echogenoic
      hilus reflex in 15 nodes; 44.1%). Administration of the galactose-based
      ultrasound contrast enhancer facilitated the assessment of hilar vessels, which
      projected to the echogenoic hili, respectively, actually additionally visualized
      a hilar vascularity in 10 of the 34 lymph nodes compared with conventional
      Doppler. Measured Doppler indices gave not a significant clue for identifying
      reactive lymph nodes or for differential diagnosis. CONCLUSIONS: Qualitative
      sonomorphologic assessment of characteristic sonomorphologic features of reactive
      lymph nodes may serve as a valuable tool for examining reactively enlarged lymph
      nodes. Administration of an ultrasound echo enhancer allows the assessment of a
      characteristic nodal vascularity in reactive lymph nodes and were superior to
      conventional B-mode and conventional Doppler sonography.

PMID- 9525754
TI  - Magnetic resonance imaging relaxation times and gadolinium-DTPA relaxivity values
      in human cerebrospinal fluid.
AB  - RATIONALE AND OBJECTIVES: This study was conducted to prove the feasibility of
      using cerebrospinal fluid (CSF) T1 and T2 measurements to assess the blood-brain
      barrier integrity in disease states not noted for focal blood-brain barrier
      disruption, such as Alzheimer's disease. METHODS: T1 and T2 of human CSF samples
      were measured with and without gadolinium Gd-DTPA over a concentration range of
      1.98 x 10(-3) to 6.32 mM, in a GE 1.5-T Signa scanner. RESULTS: T1 and T2 of
      human CSF without Gd-DTPA were measured as 2.39 and 0.23 s. K1 and K2 were
      calculated as 6.25 and 6.74 mM(-1) s(-1). The lowest Gd-DTPA concentration with
      measurable T1 and T2 was 1.98 x 10(-3) mM. There is no statistically significant
      difference in T2 and K2 at different repetition times. CONCLUSIONS: This work
      demonstrates that a single measurement of relaxation times after contrast
      enhanced magnetic resonance imaging could be used to determine the Gd-DTPA
      concentration in CSF. It may thus be feasible, using this technique, to measure
      intersubject and intraregional variability in the quantity of Gd-DTPA transferred
      across the blood-brain barrier after intravenous injection of contrast agent.

PMID- 9525755
TI  - Quantitative assessment of the muscles of the rotator cuff with magnetic
      resonance imaging.
AB  - RATIONALE AND OBJECTIVES: The purpose of this study was to establish a magnetic
      resonance (MR) imaging standard for quantification of the muscles of the rotator
      cuff. METHODS: Parasagittal T1-weighted turbo spin-echo images of the shoulder
      were obtained in 70 asymptomatic subjects (35 women, 35 men; age range: 21-70
      years, mean: 45 years). Standardized cross-sectional areas (rotator cuff muscle
      areas divided by the area of the supraspinatus fossa) and standardized signal
      intensities (related to signal intensities of the teres major muscle) were
      measured and compared with 30 patients with different stages of rotator cuff
      tears and 10 patients with glenohumeral instability. In addition, a so-called
      tangent sign was evaluated with the hypothesis that a healthy supraspinatus
      muscle crosses a line (tangent) drawn through the superior borders of the
      scapular spine and the superior margin of the coracoid. RESULTS: Cross-sectional
      areas of the muscles of the rotator cuff were variable in asymptomatic subjects.
      Cross-sectional areas (but not signal intensities) did discriminate patients with
      different stages of rotator cuff tears from asymptomatic subjects. The tangent
      sign was negative in all asymptomatic subjects but positive in four and nine of
      10 patients with medium and large rotator cuff tears, respectively. CONCLUSIONS:
      A method for quantification of the muscles of the rotator cuff using MR imaging
      is presented. Cross-sectional areas can be used for quantification of the muscles
      of the rotator cuff. The tangent sign is a useful MR sign for atrophy of the
      supraspinatus muscle.

PMID- 9525756
TI  - Evaluation of altered myocardial high energy phosphate metabolism in patients on
      maintenance dialysis using phosphorus-31 magnetic resonance spectroscopy.
AB  - RATIONALE AND OBJECTIVES: Assessment of left ventricular metabolism and function
      is important in patients on maintenance dialysis because congestive heart failure
      occurs quite frequently and has a poor prognosis. The purpose of this study was
      to evaluate the changes of myocardial high energy metabolism in dialysis patients
      by using phosphorus-31 (31P) magnetic resonance (MR) spectroscopy. METHODS:
      Phosphorus-31 spectra were obtained from anteroseptal wall of the heart in six
      normal subjects (mean age, 24 +/- 1 years) and 14 dialysis patients (mean age, 52
      +/- 11 years), using a 1.5-tesla clinical MR system. Four patients had previous
      history of heart failure. Echocardiography was performed in all patients to
      evaluate left ventricular (LV) hypertrophy and LV function. RESULTS: The averaged
      ratio of phosphocreatine (PCr)/beta-adenosine triphosphate (beta-ATP) in dialysis
      patients (1.15 +/- 0.25 mean +/- standard deviation), was significantly lower
      than that in healthy subjects (1.63 +/- 0.21; P < 0.01). There was no significant
      difference in PCr/beta-ATP ratios between the non-LV hypertrophy group (1.21 +/-
      0.24; n = 7) and the LV hypertrophy group (1.09 +/- 0.24; n = 7). The averaged
      PCr/beta-ATP ratio in four patients with history of heart failure (0.96 +/- 0.18)
      was significantly lower than that of the 10 patients without history of heart
      failure (1.22 +/- 0.23; P < 0.05). CONCLUSIONS: These results indicate that
      patients on maintenance dialysis have decreased PCr/beta-ATP ratio and 31P MR
      spectroscopy can provide noninvasive assessment of altered high energy phosphate
      metabolism.

PMID- 9525757
TI  - Utility of electron microscopy in the assessment of transthoracic needle lung
      biopsy specimens.
AB  - RATIONALE AND OBJECTIVES: The authors determine the usefulness of electron
      microscopy (EM) in the workup of patients with certain intrathoracic masses
      undergoing transthoracic needle biopsy (TNB). METHODS: Over a 4-year period, 1603
      patients underwent TNB at our institution. Of these, 79 had EM examination of the
      aspirated material. The study is a retrospective review of this latter group.
      Previous use of EM for TNB had suggested that it may he helpful in those with
      pleural, chest wall, and mediastinal lesions. The 40 men and 39 women had
      pulmonary (n = 49), mediastinal (n = 17), pleural (n = 10), and chest wall (n =
      3) lesions. RESULTS: The adequate specimen rate was 59% (47 of 79) for light
      microscopy (LM) and 37% (29 of 79) for EM. Of the 28 patients with satisfactory
      specimens for both LM and EM, the correct diagnosis was obtained by LM 79% (22 of
      28) and EM 96% (27 of 28) of the time. Electron microscopy was most helpful in
      patients with mediastinal (6 of 6 correct versus 3 of 6 for LM) and pleural (3 of
      3 versus 1 of 3) lesions. CONCLUSIONS: In specific circumstances, EM can be a
      very useful adjunct to LM in patients undergoing TNB. Problems with sample
      adequacy must be addressed.

PMID- 9525758
TI  - In vitro and animal experiments in contrast media testing.

PMID- 9525760
TI  - Particle motion within in vitro models of stenosed internal carotid and left
      anterior descending coronary arteries.
AB  - Asymmetric 75% and 95% area reduction, transparent Sylgard stenotic models were
      operated under internal carotid artery (ICA) [Womersley parameter, alpha=5.36,
      Re(mean) =213 and 180, respectively, and Re(peak)=734 and 410, respectively] and
      left anterior descending coronary artery (LAD) flow wave forms (alpha=2.65,
      Re(mean)=59 and 57, respectively, and Re(peak)= 137 and 94, respectively) to
      evaluate the effect of these conditions on particle residence times downstream of
      the stenoses. Amberlite particles (1.05 g/cm3, 400 microm) were added to the
      fluid to simulate platelets and their motion through the stenotic region and were
      traced using a laser light sheet flow visualization method with pseudo-color
      display. Two-dimensional (2D) particle motions were recorded and particle washout
      in the stenotic throat and downstream section were computed for all cases. All
      four model cases demonstrated jetting through the stenosis which followed an
      arching pattern around a large separation zone downstream. Considerable mixing
      was observed within these vortex regions during high flow phases. Particle
      washout profiles showed no clear trend between the degrees of stenosis although
      particles downstream of the stenoses tended to remain longer for LAD conditions.
      The critical washout cycle (1% of particles remaining downstream of the
      stenosis), however, was longer for the 95% stenoses cases under each flow
      condition due to the larger protected region immediately downstream and maximal
      for the LAD 95% case. Results of this study suggest that particle residence times
      downstream of 75% and 95% stenoses (approximately 3-6 s for ICA and approximately
      8-10 s for LAD) exceed the minimum time for platelet adhesion (approximately 1 s)
      for at least 1% of cells and, thus, may be sufficient to initiate thrombus
      formation under resting conditions.

PMID- 9525761
TI  - Influence of vasoactive drugs on wall shear stress distribution in the abdominal
      aortic bifurcation: an in vitro study.
AB  - The present study compares the wall shear stress (rate) distribution in a
      compliant aortic bifurcation model under three different hemodynamic states:
      normal state, angiotensin II infusion state (vasoconstrictor), and isoproterenol
      infusion state (vasodilator). Using a Newtonian blood analog fluid, flow wave
      forms corresponding to each flow state were generated in an in vitro flow loop
      and a photographic flow visualization technique was employed to measure wall
      shear rate. The results indicate a zone of low mean wall shear stress and highly
      oscillatory shear stress on the outer (lateral) wall of the bifurcation. In this
      zone, the mean wall shear stress became negative for all three hemodynamic states
      indicating flow separation. However, the spatial extent of the flow separation
      zone was not affected significantly by the flow state. The study also revealed a
      large spatial variation of the phase angle between the hoop strain
      (circumferential strain due to radial artery expansion) and the wall shear
      stress, the two main mechanical stimuli acting on endothelial cells which affect
      their biology. In the zone of low mean wall shear stress on the outer wall, the
      two stimuli were more out of phase relative to the mother branch, whereas they
      were less out of phase (by about 50 degrees) on the inner wall (flow divider
      side). This phase angle was affected significantly by the flow state. For
      angiotensin II, the phase angle reached a maximum of 125 degrees in the low mean
      shear zone while the maximum was 94 degrees and 66 degrees for the normal and
      isoproterenol states, respectively. Our observation that large phase angles
      between the hoop strain and wall shear stress wave forms are localized in the low
      shear stress region where atherosclerotic disease occurs suggests the possible
      physiological relevance of this phase angle to the development of
      atherosclerosis.

PMID- 9525759
TI  - A strain device imposing dynamic and uniform equi-biaxial strain to cultured
      cells.
AB  - The objective of this study is to design a new apparatus to allow the control of
      the magnitude and frequency of dynamic stretch applied uniformly to cells
      cultured on a silicon elastic membrane. The apparatus is designed to produce equi
      biaxial dynamic stretches with area changes ranging from 0% to 55% and
      frequencies ranging from 0 to 2 Hz. Homogeneous finite strain analysis using
      triangles of markers was performed to compute the symmetric two-dimensional
      Lagrangian strain tensor on the membrane. Measurements of strain in both static
      and dynamic conditions showed that the shear component of the strain tensor (Erc)
      was near zero, and that there was no significant difference between radial (Err)
      and circumferential (Ecc) components, indicating the attainment of equi-biaxial
      strain. Bovine aortic endothelial cells were transiently transfected with a
      chimeric construct in which the luciferase reporter is driven by TPA-responsive
      elements (TRE). The transfected cells cultured on the membrane were stretched.
      The luciferase activity increased significantly only when the cells were
      stretched by 15% or more in area. Cells in different locations of the membrane
      showed similar induction of luciferase activities, confirming that strain is
      uniform and equi-biaxial across the membrane.

PMID- 9525762
TI  - Mechanism of Ca++ release from the sarcoplasmic reticulum: a computer model.
AB  - The proposed model describes myocyte calcium (Ca++) cycling, emphasizing the
      kinetics of sarcoplasmic reticulum (SR) Ca++ release channels. The suggested SR
      channel regulating mechanism includes two types of Ca++ binding sites: (1) low
      affinity sites with high binding rates, regulating the opening of Ca++ channels
      and (2) high affinity sites with low binding rates, which regulate their closing.
      The amount of Ca++ released from the SR and the peak value of Ca++ ion
      concentration [Ca++] in the cytoplasm were found to depend on the rate of the
      increase of [Ca++], similar to Ca++ induced Ca++ release experiments. The model
      describes spontaneous release of Ca++ from overloaded SR. The dependence of the
      control mechanism on the activating and inactivating sites is substantiated by
      simulations of ryanodine intervention, providing results similar to experimental
      results. Simulations under conditions of isolated SR vesicles produced Ca++
      release results similar to measured data. Consequently, it is suggested that the
      recovery of Ca++ release channels represents the rate limiting factor in the
      process of mechanical restitution.

PMID- 9525763
TI  - Sensitivity analysis for evaluating nonlinear models of lung mechanics.
AB  - We present a combined theoretical and numerical procedure for sensitivity
      analyses of lung mechanics models that are nonlinear in both state variables and
      parameters. We apply the analyses to a recently proposed nonlinear lung model
      which incorporates a wide range of potential nonlinear identification conditions
      including nonlinear viscoelastic tissues, airway inhomogeneities via a parallel
      airway resistance distribution function, and a nonlinear block-structure
      paradigm. Additionally, we examine a system identification procedure which fits
      time- and frequency-domain data simultaneously. Model nonlinearities motivate
      sensitivity analyses involving numerical approximation of sensitivity
      coefficients. Examination of the normalized sensitivity coefficients provides
      direct insight on the relative importance of each model parameter, and hence the
      respective mechanism. More formal quantification of parameter uniqueness requires
      approximation of the paired and multidimensional parameter confidence regions.
      Combined with parameter estimation, we use the sensitivity analyses to justify
      tissue nonlinearities in modeling of lung mechanics for healthy and airway
      constricted conditions, and to justify both airway inhomogeneities and tissue
      nonlinearities during bronchoconstriction. The tools in this paper are general
      and can be applied to a wide class of nonlinear models.

PMID- 9525764
TI  - Nonparametric block-structured modeling of lung tissue strip mechanics.
AB  - Very large amplitude pseudorandom uniaxial perturbations containing frequencies
      between 0.125 and 12.5 Hz were applied to five dog lung tissue strips. Three
      different nonlinear block-structured models in nonparametric form were fit to the
      data. These models consisted of (1) a static nonlinear block followed by a
      dynamic linear block (Hammerstein model); (2) the same blocks in reverse order
      (Wiener model); and (3) the blocks in parallel (parallel model). Both the
      Hammerstein and Wiener models performed well for a given input perturbation, each
      accounting for greater than 99% of the measured stress signal variance. However,
      the Wiener and parallel model parameters showed some dependence on the strain
      amplitude and the mean stress. In contrast, a single Hammerstein model accounted
      for the data at all strain amplitudes and operating stresses. A Hammerstein model
      featuring a fifth-order polynomial static nonlinearity and a linear impulse
      response function of 1 s duration accounted for the most output variance
      (99.84%+/-0.13%, mean+/-standard deviations for perturbations of 50% strain at
      1.5 kPa stress). The static nonlinear behavior of the Hammerstein model also
      matched the quasistatic stress-strain behavior obtained at the same strain
      amplitude and operating stress. These results show that the static nonlinear
      behavior of the dog lung tissue strip is separable from its linear dynamic
      behavior.

PMID- 9525765
TI  - Current patterns and electrode types for single-source electrical impedance
      tomography of the thorax.
AB  - Electrical impedance tomography (EIT) estimates the spatial distribution of the
      electrical tissue properties in a cross section of the body. In the present
      study, we investigated how the quality of static thoracic images obtained from
      EIT systems with a single current source and sink is affected by the current
      pattern employed in the presence of measurement noise. The reconstructed images
      best reproduced our computational phantom when current source and sink were
      placed at neighboring electrodes. In this case, the mean squared reconstruction
      error was an order of magnitude smaller than for all other patterns of current
      injection studied. At a signal-to-noise ratio of 50 dB, 60% of the
      reconstructions converged successfully with source and sink at neighboring
      electrodes, while only 10% or less converged for all other configurations. We
      relate these results to the fact that neighboring currents strengthen the
      diagonal structure in the Hessian matrix of the iterative reconstruction process
      that we employed. We also tested the effects on the reconstruction error of the
      number and type of electrodes. We found that "compound electrodes" that permit
      voltage measurement at the site of current injection did not yield any practical
      improvement of the image quality. In contrast, doubling the number of boundary
      electrodes reduced the reconstruction error by almost two orders of magnitude.

PMID- 9525766
TI  - An adaptive filter to reduce cardiogenic oscillations on esophageal pressure
      signals.
AB  - Measurements of pressure swings in the esophagus (Pes) can be used to estimate
      variables of clinical importance, e.g., intrinsic positive end-expiratory
      pressure (PEEPi). Unfortunately, cardiogenic oscillations frequently corrupt Pes
      and complicate further analysis. Due to significant band overlap with the
      respiratory component of Pes, cardiogenic oscillations cannot be suppressed
      adequately using standard filtering techniques. In this article, we present an
      adaptive filter that employs the electrocardiogram to identify and suppress the
      cardiogenic oscillations. This filter was tested using simulated data, where the
      variance accounted for relative to the simulated respiratory pressure swings
      increased from as low as 55% for the unfiltered Pes signal to over 95% when the
      adaptive filter was used. In patient data, the adaptive filter reduced the
      apparent cardiogenic oscillations without noticeably distorting the sharp
      deflections in Pes due to respiration. Furthermore, the filter suppressed peaks
      in the Fourier transform of Pes at integer multiples of the heart rate, while the
      remaining frequencies remained largely unchanged. During stable breathing, the
      standard deviation of PEEPi was reduced by between 44% and 71% in these four
      patients when the filter was used. We conclude that our filter removes a
      significant fraction of the cardiogenic oscillations that corrupt records of Pes.

PMID- 9525767
TI  - Quantification of the passive mechanical properties of the resting platelet.
AB  - Sudden coronary artery occlusion is one of the leading causes of death. Several
      in vitro models have been used to study the relationship between hemodynamic
      forces and platelet function. However, very few in vivo studies exist that fully
      explore this relationship due to the lack of rheologic data for the platelet. For
      this purpose, micropipette aspiration techniques were used in the present study
      to determine the mechanical properties of platelets. The data were analyzed by
      two mathematical models: (1) an erythrocyte-type membrane model which yielded a
      platelet shear modulus of 0.03+/-0.01 dyn cm[-1] (mean+/-SD) and a viscous
      modulus of 0.12+/-0.04 dyn s cm[-1]. (2) An endothelial-type cell model which
      approximated the platelet Young's modulus to be 1.7+/-0.6 x 10(3) dyn cm(-2) with
      a viscous modulus of 1.0+/-0.5 x 10(4) dyn s cm(-2). The endothelial-type cell
      model more accurately describes the mechanics occurring at the micropipette tip
      and permits more appropriate assumptions to be made in quantifying the rheologic
      properties of a platelet. Results from this study can be integrated into
      numerical models of blood flow in stenosed coronary arteries to elucidate the
      impact of local hemodynamics on platelets and thrombus formation in coronary
      artery disease.

PMID- 9525768
TI  - An admissible solution approach to inverse electrocardiography.
AB  - The goal of the inverse problem of electrocardiography is noninvasive
      discrimination and characterization of normal/abnormal cardiac electrical
      activity from measurements of body surface potentials. Smoothing and attenuation
      in the torso volume conductor cause the problem to be ill posed. Standard
      regularized solutions employ an a priori constraint to achieve reliability and
      may be biased by the constraint chosen as well as the regularization parameter
      used to weight it. In this paper, we describe an approach that reformulates this
      inverse problem as the search for a solution that is a member of an admissible
      solution set; admissibility is defined in terms of the available constraints. In
      principle, this approach can utilize as many constraints as may be available,
      unlike standard techniques which do not easily permit the use of multiple
      constraints. No regularization parameter is required; instead, we need to choose
      the nature and size of the constraint sets. Constraints described include several
      spatial constraints, weighted constraints, and temporal constraints. We describe
      a solution approach based on iterative convex optimization, and the algorithm-
      the ellipsoid algorithm--which we have used. Accuracy and feasibility of the
      method are illustrated with simulation results using dipole sources and measured
      epicardial potentials.

PMID- 9525769
TI  - Subband modeling of the human cardiovascular system: new insights into
      cardiovascular regulation.
AB  - We present a new approach to cardiovascular analysis based on a well-known signal
      processing technique, namely, the frequency subband decomposition. The subbands
      are chosen in accordance with physiological standards: (1) 0-0.04 Hz, (2) 0.04
      0.15 Hz, (3) 0.15-0.4 Hz. It is shown that such a pre-processing drastically
      improves the accuracy of the analysis and introduces a new direction in the
      understanding of the relationships between cardiovascular signals.

PMID- 9525770
TI  - Two methods for calculating the responses of photoreceptors to moving objects.
AB  - The responses of photoreceptor cells to moving stimuli are crucial to
      understanding motion detection in visual systems. However, these responses are
      not well characterized quantitatively because they result from a combination of
      spatial optical behavior in the lens systems with temporal behavior in the
      phototransduction mechanism. While both these processes can now be modeled quite
      well by relatively simple equations, their combination cannot be easily obtained
      in a closed form. Here, we present two approaches to this problem, based on well
      established models for the lens and photoreceptors systems of the fly compound
      eye. The first approach leads to a recursive formula for predicting the
      photoreceptor response to a moving point object. The second method is
      approximate, but almost equally accurate and more rapid.

PMID- 9525771
TI  - Iterative fast orthogonal search for modeling by a sum of exponentials or
      sinusoids.
AB  - Accurate sinusoidal series models of biological time-series data may be obtained
      using a modeling algorithm known as fast orthogonal search (FOS). FOS does not
      require equally spaced data, and can resolve sinusoidal frequencies much more
      closely spaced than can a discrete Fourier transform. FOS has been less
      successful at obtaining accurate exponential series models. We here consider a
      modification of FOS in which iteration of the original procedure is used to
      further reduce the mean-squared error (m.s.e.) between model and data,
      approaching a minimum in the m.s.e. Iteration of the FOS procedure greatly
      improves the accuracy of estimated exponential series models. The application of
      iterative FOS (IFOS) to exponential and sinusoidal series models is described.
      Finally, the use of FOS and IFOS procedures for finding a single model from the
      results of multiple experiments is described.

PMID- 9525773
TI  - Immunobiology of lipopolysaccharide (LPS) and LPS-derived immunoconjugates
      vaccinate mice against Salmonella typhimurium.
AB  - The immunobiology of lipopolysaccharide (LPS) of Salmonella typhimurium LT2-71
      was studied in its native, modified and conjugated states using mice as the
      experimental model. An alkali-treated detoxified fraction of LPS (D-LPS) was
      found to be not only non-toxic but also equally immunogenic, like LPS. In
      addition D-LPS alone or conjugated with enterotoxin or hemolysin was also non
      pyrogenic and non-indurogenic. The immunoprophylactic activity of D-LPS
      conjugates to a 100 ID50 challenge dose of S. typhimurium was also higher than
      that of detoxified LPS or native LPS.

PMID- 9525772
TI  - A unified method for calculating the center of pressure during wheelchair
      propulsion.
AB  - The measurement of the center of pressure (COP) has been and continues to be a
      successful tool for gait analysis. The definition of a similar COP for wheelchair
      propulsion. however, is not straightforward. Previously, a COP definition similar
      to that used in force plate analysis had been proposed. Unfortunately, this
      solution has the disadvantage of requiring a separate COP definition for each
      plane of analysis. A definition of the generalized center of pressure (GCOP)
      which is consistent in all planes of analysis is derived here. This definition is
      based on the placement of a force-moment system, equivalent to the force-moment
      system at the hub, on a line in space where the moment vector (wrench moment) is
      parallel to the force vector. The parallel force-moment system is then
      intersected with three planes defined by anatomical landmarks on the hand. Data
      were collected using eight subjects at propulsion speeds of 1.34 m/s and 2.24 m/s
      (1.34 m/s only for subject 1, 0.894 m/s and 1.79 m/s for subject 8). Each subject
      propelled a wheelchair instrumented with a SMARTwheel. A PEAK 5 video system was
      used to determine the position of anatomical markers attached to each subject's
      upper extremity. The GCOP in the transverse plane of the wrist formed clusters
      for all subject's except subject 2 at 1.34 m/s. The clustering of the GCOP
      indicates that the line of action for the force applied by the hand is
      approximately perpendicular to the transverse plane through the wrist. When
      comparing the magnitude of the moment vector part of the wrench with the moment
      of the force vector of the wrench about the hub, the wrench moment is
      approximately an order of magnitude smaller. This indicates that the role of the
      wrist for wheelchair propulsion is primarily to stabilize the force applied by
      the arm and shoulder.

PMID- 9525774
TI  - Structural and immunochemical studies of two cross-reactive Proteus mirabilis O
      antigens, O6 and O23, containing beta1-->3-linked 2-acetamido-2-deoxy-D
      glucopyranose residues.
AB  - A marked serological cross-reactivity was observed by ELISA and a precipitation
      test between anti-Proteus mirabilis O23 serum and the lipopolysaccharide as well
      as the O-specific polysaccharide from the Proteus mirabilis strain belonging to
      serogroup O6. The structures of the O-specific polysaccharides were elucidated
      using chemical and NMR spectroscopic analyses, and the only common component, 2
      acetamido-2-deoxy-beta-D-glucopyranose (beta-D-GlcNAc), was revealed, which was
      suggested to be responsible for the cross-reactivity observed. Both anti-O23 and
      anti-O6 sera were shown to react with 1, 3-Linked beta-D-GlcNAc-containing O
      antigen from Salmonella enterica ssp. arizonae O59 also. The lack of reactivity
      of Smith-degraded P. mirabilis O6 O-specific polysaccharide with homologous
      antiserum indicated the crucial role of alpha-D-glucuronic acid in specific
      antibody binding.

PMID- 9525775
TI  - Shotgun cloning and characterization of the thymidylate synthase-encoding gene
      from Mycobacterium bovis BCG.
AB  - The shotgun cloning of a Mycobacterium bovis BCG (BCG) genome into pBluescript SK
      (+) successfully yielded a 0.9 kbp fragment, confirming the ability of
      Escherichia coli thyA mutant MH2702 to grow in a thymine-depleted medium. This
      DNA fragment contained a gene homologous to the thymidylate synthase (TS)
      encoding genes (thyA) of other organisms. An inverted repeat sequence and open
      reading frame (ORF) were observed at the upstream region of the thyA. A computer
      analysis revealed that the protein encoded by this ORF possessed a structure
      unique for a DNA binding protein.

PMID- 9525776
TI  - Biochemical and immunological analyses of the flagellin of Clostridium
      tyrobutyricum ATCC 25755.
AB  - The monoclonal antibody 21E7-B12 (IgG3) can be used in a direct method of
      Clostridium tyrobutyricum detection based on an immunoenzymatic assay.
      Immunoelectron microscopy demonstrated that the 21E7-B12 antibody recognized the
      surface-exposed epitopes on the flagellar filaments of C. tyrobutyricum. After
      flagellar extraction, the purified flagellin showed an apparent molecular mass of
      46 kDa with an isoelectric point of 3.6. Sugar staining, mild periodate oxidation
      and beta-elimination experiments showed that the flagellin was glycosylated and
      that the 21E7-B12 epitope was located in the sugar moiety. Amino acid composition
      showed that the flagellar filament protein contained a high percentage of serine
      and threonine, while proline was absent. The first 23 residues of the N-terminal
      were determined and sequence homology with other flagellins was found.

PMID- 9525778
TI  - Adhesive property of toxin-coregulated pilus of Vibrio cholerae O1.
AB  - The adhesive property of toxin-coregulated pilus (TCP) to the human intestine
      jejunum), and whether or not TCP mediates the adhesion of Vibrio cholerae 395
      organisms to the intestinal epithelium were investigated using visually proving
      methods. The purified TCP did not agglutinate human erythrocytes nor adhere to
      the surface of human intestinal epithelium. V. cholerae 395 adhered to the
      epithelium, but the adhesion was not inhibited by blocking the pili with the Fab
      fraction of anti-TCP IgG. The organisms adhered to the intestine treated with
      purified TCP in advance, as well as to the intact intestine. These findings
      suggest that TCP is not involved in the adhesion of these organisms to the
      intestinal epithelium.

PMID- 9525777
TI  - The inhibitory effect of Staphylococcus epidermidis slime on the phagocytosis of
      murine peritoneal macrophages is interferon-independent.
AB  - The extracellular slime produced by Staphylococcus epidermidis has been shown to
      interfere with several human neutrophil functions in vitro, such as chemotaxis,
      degranulation and phagocytosis. Slime production has been suggested as a useful
      marker for clinically significant infections with coagulase-negative
      Staphylococcus. Since the main role of macrophages in defense mechanisms is
      phagocytosis, the effect of slime on the phagocytic activity of macrophages was
      investigated. The phagocytic activity of murine peritoneal macrophages treated
      with slime in vitro decreased in a dose-dependent fashion. A similar decrease was
      also observed in macrophages isolated from mice that had previously received
      intraperitoneal injection of slime. To investigate whether interferon also plays
      a role in this process, mice were treated with interferon or an interferon
      inducer, polyinosinic-polycytidylic acid (poly I:C), together with slime before
      macrophage isolation. The slime-suppressed phagocytic activity of macrophages was
      partially relieved by both agents, and the recovery effect of poly I:C in slime
      suppressed phagocytosis of macrophages in vivo might be attributed to the
      increased interferon level in peritoneal fluid and sera. However, when slime was
      given to poly I:C-pretreated mice, the phagocytic activity remained suppressed.
      Thus, it appears that slime is able to suppress the phagocytic activity of
      macrophages regardless of the state of macrophage activation by poly I:C. The
      results suggest that the inhibition of phagocytosis by S. epidermidis slime may
      be independent from the activation of interferon.

PMID- 9525779
TI  - Response of blood platelets to Proteus mirabilis lipopolysaccharide.
AB  - The effects of the lipopolysaccharide (LPS) of Proteus mirabilis on the
      production of thiobarbituric acid reactive substances (TBARS) and the generation
      of superoxide radicals (O2) by pig blood platelets were studied in vitro. The
      effect of LPS on TBARS formation in platelets was dependent on the concentration
      of endotoxin. LPS at concentrations above 0.1 microg/10(8) platelets caused the
      production of TBARS concomitant with the generation of superoxide radicals. The
      responses of platelets to LPS suggest that endotoxin, like thrombin (a strong
      platelets agonist), stimulates an enzymatic cascade of platelet arachidonate via
      cyclooxygenase and produces thromboxane A2 (TXA2) concomitant with
      malonyldialdehyde (MDA).

PMID- 9525780
TI  - Detection of Coxiella burnetii from dust in a barn housing dairy cattle.
AB  - We attempted to detect Coxiella burnetii in dust samples collected from a barn
      housing dairy cattle by the polymerase chain reaction (PCR) method. Ten dust
      samples (five from ventilation fans and five from crossbeams) were collected from
      two areas in a barn on a farm near Sapporo, Hokkaido. C. burnetii was detected in
      5 of the 10 dust samples. It was believed that aerial contamination by C.
      burnetii occurred in the barn.

PMID- 9525781
TI  - Development of reference procedures for broth microdilution antifungal
      susceptibility testing of yeasts with standardized endpoint determination.
AB  - Standard guidelines for the broth microdilution antifungal susceptibility testing
      of amphotericin B, flucytosine, fluconazole, miconazole and itraconazole are
      reported. These are a modification of the method developed by the National
      Committee for Clinical Laboratory Standards (NCCLS) on the following two points:
      standardization of the means of endpoint determination and the inclusion of
      miconazole and itraconazole in the testing. MIC was determined to be when the
      positive control had a turbidity of 0.2 at the 630 nm wavelength. The endpoint
      was 80% inhibition for azoles and 100% inhibition for other drugs. The method
      provided good reproducibility, and a wide range of MIC distribution was observed
      in all antifungal agents except amphotericin B.

PMID- 9525782
TI  - In vitro susceptibility of Chlamydia pecorum to macrolides, tetracyclines,
      quinolones and beta-lactam.
AB  - The in vitro susceptibility of Chlamydia pecorum to two macrolides
      (clarithromycin and erythromycin), two tetracyclines (doxycycline and
      minocycline), two quinolones (ofloxacin and ciprofloxacin) and one beta-lactam
      (ampicillin) was determined. The MICs were 0.004 to 0.008 microg/ml for
      clarithromycin, 0.008 to 0.031 microg/ml for doxycycline and minocycline, 0.063
      to 0.125 microg/ml for erythromycin, 0.25 to 0.5 microg/ml for ofloxacin and 0.25
      to 1.0 microg/ml for ciprofloxacin. The MIC for ampicillin was greater than 1,024
      microg/ml. The results show clarithromycin and doxycycline are the two most
      effective drugs against C. pecorum.

PMID- 9525783
TI  - Accumulation kinetics of viral gene products in cauliflower mosaic virus-infected
      turnip protoplasts.
AB  - The expression of cauliflower mosaic virus (CaMV) genes was studied in a turnip
      protoplast system. Six CaMV-encoded gene products were detected in infected
      turnip protoplasts by means of Western blotting. The infected turnip protoplasts
      showed different patterns of protein accumulation; e.g. an open reading frame
      (ORF) I-encoded movement protein, an ORF V-encoded reverse transcriptase and an
      ORF VI-encoded posttranscriptional transactivator representing the early
      accumulated proteins, an ORF II-encoded aphid transmission factor and an ORF IV
      encoded coat protein the late accumulated proteins and an ORF III-encoded DNA
      binding protein the intermediate protein. The results suggest that the expression
      of CaMV genes is differentially regulated.

PMID- 9525786
TI  - Back to the future.

PMID- 9525785
TI  - Follow-up study of hypervariable region sequences of the hepatitis C virus (HCV)
      genome in an infant with delayed anti-HCV antibody responses.
AB  - An infant born prematurely and infected with hepatitis C virus (HCV) one month
      after birth was followed for 4.5 years. The patient did not produce detectable
      anti-HCV antibodies until two years after the onset of hepatitis. Before
      seroconversion, a single clone of HCV, as determined by quasispecies of the
      hypervariable region (HVR) of the HCV genome, was almost exclusively found in the
      serum. After seroconversion, however, another distinct lineage of HCV clones
      replaced it within half a year. As HCV infection persisted further in the
      presence of anti-HCV antibodies, many derivatives of both sequence lineages
      emerged to exhibit the typical quasispecies feature of HVR sequences. Neither
      seroconversion nor the changes in HVR sequences influenced the serum
      aminotransferase titers.

PMID- 9525784
TI  - Infectivity and immunogenicity of SIVmac/HIV-1 chimeric viruses (SHIVs) with
      deletions in two or three genes (vpr, nef and vpx).
AB  - Two SHIVs with two or three genes deleted (SHIV-drn and SHIV-dxrn) were
      constructed. The inoculation of monkeys with SHIV-drn resulted in short-term
      viremia, but inoculation with SHIV-dxrn did not. At 68 weeks post-inoculation,
      the monkeys were reinoculated with a 100-fold higher dose of each SHIV, but none
      showed viremia. Killer cell activities against HIV-1 Env were detected in the
      SHIV-drn- and SHIV-dxrn-inoculated monkeys. Cross-reactive killer activity
      against HIV-1 Gag and SIVmac Gag was observed in one monkey. Antibodies were not
      detected in the SHIV-dxrn-inoculated monkeys, but the SHIV-drn-inoculated monkeys
      showed an anamnestic antibody reaction. These data indicate that SHIV-drn is
      infectious to and immuno-inducible in macaques but SHIV-dxrn is not.

PMID- 9525787
TI  - Routine treatment of adult depression.

PMID- 9525788
TI  - Mental health clinicians' role in responding to critical incidents in the
      community.

PMID- 9525789
TI  - Combining telephone peer counseling and professional services for clients in
      intensive psychiatric rehabilitation.

PMID- 9525790
TI  - Gender sensitivity in health care for elderly men and women.

PMID- 9525791
TI  - The effects of public managed care on patterns of intensive use of inpatient
      psychiatric services.
AB  - OBJECTIVE: The study examined the characteristics of frequent users of inpatient
      treatment under public-sector managed care in Massachusetts between 1992 and 1995
      and explored whether their pattern of inpatient utilization affected their
      overall use of hospital days. METHODS: Individuals with five or more admissions
      in any of four fiscal years (1992 to 1995) were identified using the
      Massachusetts Department of Mental Health client tracking system. The demographic
      and clinical characteristics of these patients and the types of hospitals they
      used were compared with those of all patients in case management programs who had
      a hospital admission but who did not meet study criteria for multiple admissions.
      RESULTS: Compared with other patients, patients with multiple admissions were
      more likely to be young Caucasian females with personality disorder and a history
      of substance abuse but not a current substance use disorder. They tended to be
      lower functioning as measured by the Georgia Role Functioning Scale (GRFS) and to
      have higher levels of distress, as measured by the global personal distress
      portion of the GRFS. They made up 6 to 8 percent of all clients with a
      psychiatric admission who were enrolled in a case management program, but they
      accounted for 21 to 27 percent of all admissions in the four fiscal years.
      Patients with multiple admissions had significantly longer lengths of stay when
      admitted to a hospital where they had not been previously admitted in the past 12
      months. CONCLUSIONS: States setting up public-sector managed care or revising
      existing public-sector managed care contracts should ensure that subpopulations
      of persons at high risk for multiple admissions receive special attention. They
      should also create networks of inpatient providers to enable frequent users of
      acute care facilities to return to the same facility that previously discharged
      them.

PMID- 9525792
TI  - Increased contact with community mental health resources as a potential benefit
      of family education.
AB  - OBJECTIVE: This study examined the hypothesis that families of adults with severe
      mental illness who participate in either a group family education workshop or
      individual family consultation will try to seek more assistance from community
      services than those in a control group assigned to a waiting list. METHODS: A
      total of 225 family members who agreed to participate in the study were randomly
      assigned to one of three conditions: a ten-week group workshop, individual family
      consultation, or a waiting list (control group). Family members were interviewed
      about the extent of their contact with mental health professionals, providers,
      and community resources at baseline, termination of the interventions, and at six
      months after termination. RESULTS: No differences were found between conditions
      in the extent of family members' contact with three types of services:
      conventional, psychosocial, and ancillary mental health services. CONCLUSIONS:
      Neither of the educational interventions produced any change in behaviors of
      families seeking advice and assistance on behalf of their ill relative from the
      three types of services examined. Modifications in the interventions may be
      worthwhile. Increasing family members' contacts with community resources on
      behalf of their ill relative may increase the benefits of the intervention to the
      family as well as to the ill relative.

PMID- 9525795
TI  - Does outreach case management improve patients' quality of life?
AB  - OBJECTIVE: This study examined whether enhancing standard aftercare with an
      outreach case management intervention would improve patients' quality of life.
      METHODS: A sample of 292 patients discharged from an inpatient psychiatry service
      at an urban general hospital were randomly assigned either to an intervention
      group (N = 147), which received outreach case management services in addition to
      standard aftercare service, or to a control group (N = 145), which received only
      standard aftercare services. The follow-up period was 15 to 52 months.
      Individuals in both groups were reinterviewed by an independent research team
      about 21.6 months after discharge. The groups were compared using 39 measures of
      quality of life. The interviews elicited information about patients' physical
      well-being and competence in performing activities of daily living; their
      emotional well-being as shown in emotional expressiveness, sadness, suicidal
      thoughts, and substance abuse; and their interpersonal relationships, living
      arrangements, friendships, income maintenance, and employment. RESULTS: No
      difference was found between the groups on any of the quality-of-life variables.
      CONCLUSIONS: Outreach case management was not associated with improved quality of
      life.

PMID- 9525796
TI  - Abuse histories of psychiatric inpatients: to ask or not to ask?
AB  - OBJECTIVE: The literature suggests that a high prevalence of a history of sexual
      and physical abuse among psychiatric inpatients is found when researchers inquire
      about abuse directly, but that relatively low rates are found in medical records.
      This study examined rates of reported abuse among patients who were and were not
      asked about abuse at admission. METHODS: The medical records of 100 consecutive
      admissions to an urban general hospital in New Zealand were examined after the
      introduction of a new admission form with a section inquiring about abuse. Use of
      the new admission form was recommended but not mandatory. RESULTS: The abuse
      section of the new form was completed for only 17 of the 53 patients with whom
      the new form was used. Review of the medical records of all 100 consecutive
      admissions revealed a prevalence rate of 32 percent for one or more of the four
      types of abuse. However, 14 of the 17 patients (82 percent) who were asked
      directly about abuse reported having experienced abuse. Nonsignificant trends
      suggested that male gender and being more disturbed or disturbing may be
      negatively related to the probability of being asked about abuse. Men may be
      particularly unlikely to disclose childhood abuse if not asked directly.
      CONCLUSIONS: The authors recommend including inquiry about abuse in standardized
      admission procedures and providing inpatient staff with training in how and when
      to ask patients about abuse and how to effectively follow up affirmative
      responses.

PMID- 9525793
TI  - Clozapine therapy for older veterans.
AB  - OBJECTIVE: The effectiveness of clozapine treatment in a treatment-refractory
      sample of older adult veterans with primary psychosis was examined. METHODS: Data
      were collected over a five-year period for patients age 55 and older who were
      given clozapine because of a history of treatment-refractory or treatment
      intolerant psychosis. At initiation of clozapine therapy, baseline demographic,
      clinical, and psychopathology data were collected. At baseline and quarterly,
      patients' psychopathology was rated with the Brief Psychiatric Rating Scale
      (BPRS), and involuntary movements were rated with the Abnormal Involuntary
      Movement Scale (AIMS). RESULTS: The 329 patients age 55 or older who received
      clozapine during the study period represented 10 percent of all patients on
      clozapine therapy in the VA system. Of the 312 patients for whom demographic
      information was available, 294 were men and 18 were women. Overall, patients
      improved on clozapine therapy, although wide variation in drug response was
      observed. Complete BPRS and AIMS data were available for 97 patients. The 55- to
      64-year-old group had a mean improvement in total BPRS score of 19.8 percent,
      with 42.6 percent showing more than a 20 percent improvement; those age 65 and
      older had a mean improvement of 5.7 percent, with 17.2 percent showing an
      improvement greater than 20 percent. The 97 patients with complete AIMS data
      showed a mean improvement of 16.6 percent in total score. CONCLUSIONS: Clozapine
      is an important therapeutic agent for older adults with treatment-refractory
      psychosis. Patients between the ages of 55 and 64 may have a better response than
      those age 65 and older.

PMID- 9525797
TI  - The clinical characteristics of possession disorder among 20 Chinese patients in
      the Hebei province of China.
AB  - OBJECTIVE: This paper describes the clinical characteristics of 20 hospitalized
      psychiatric patients in the Hebei province of China who believed they were
      possessed. METHODS: A structured interview focused on clinical characteristics
      associated with possession phenomena was developed and administered to 20
      patients at eight hospitals in the province. All patients had been given the
      Chinese diagnosis of yi-ping (hysteria) by Chinese physicians before being
      recruited for the study. RESULTS: The subjects' mean age was 37 years. Most were
      women from rural areas with little education. Major events reported to precede
      possession included interpersonal conflicts, subjectively meaningful
      circumstances, illness, and death of an individual or dreaming of a deceased
      individual. Possessing agents were thought to be spirits of deceased individuals,
      deities, animals, and devils. Twenty percent of subjects reported multiple
      possessions. The initial experience of possession typically came on acutely and
      often became a chronic relapsing illness. Almost all subjects manifested the two
      symptoms of loss of control over their actions and acting differently. They
      frequently showed loss of awareness of surroundings, loss of personal identity,
      inability to distinguish reality from fantasy, change in tone of voice, and loss
      of perceived sensitivity to pain. CONCLUSIONS: Preliminary findings indicate that
      the disorder is a syndrome with distinct clinical characteristics that adheres
      most closely to the DSM-IV diagnosis of dissociative trance disorder under the
      category of dissociative disorder not otherwise specified.

PMID- 9525794
TI  - Substance use and psychiatric problems of homeless Native American veterans.
AB  - OBJECTIVE: This study estimated the proportion and representation of Native
      Americans among homeless veterans and compared their psychiatric and substance
      abuse problems with those of other ethnic groups of homeless veterans. METHODS:
      The study was based on data from the Department of Veterans Affairs' Health Care
      for Homeless Veterans program, a national outreach program operating at 71 sites
      across the country. Alcohol, drug, and psychiatric problems of Native American
      veterans (N=950) reported during intake assessment were compared with problems
      reported by white, black, and Hispanic veterans (N=36,938). RESULTS: Native
      Americans constituted 1.6 percent of veterans in the program. Age-adjusted
      analyses suggested that relative to the general veteran population (of which 1.3
      percent are Native Americans), Native Americans are overrepresented in the
      homeless population by approximately 19 percent. Regression analyses controlling
      for demographic characteristics found that Native American veterans reported more
      current alcohol abuse, more previous hospitalizations for alcohol dependence, and
      more days of recent alcohol intoxication than members of other ethnic groups. In
      contrast, Native American veterans reported fewer drug dependence problems than
      other minority groups and fewer current psychiatric problems and previous
      psychiatric hospitalizations than the reference group of white homeless veterans.
      CONCLUSIONS: Native Americans are overrepresented in the homeless veteran
      population. They have more severe alcohol problems than other minority groups but
      somewhat fewer psychiatric problems.

PMID- 9525798
TI  - Changes in public psychiatric hospitalization in Oregon over the past two
      decades.
AB  - OBJECTIVE: In 1988 a governor's commission in Oregon recommended dramatic changes
      in the state's approach to public psychiatric hospitalization. To evaluate the
      effect of the recommendations, this study examined characteristics of
      hospitalization for patients with schizophrenia and bipolar disorder in public
      psychiatric facilities between 1981 and 1984 and between 1991 and 1994. METHODS:
      Patients with schizophrenia and bipolar disorder (N=621) were identified as part
      of a larger study that examined civil commitment in one of Oregon's state
      hospitals in 1986. Data on the patients' hospitalizations were obtained from a
      statewide computerized mental health information system. RESULTS: The legal
      status of hospitalized patients differed between the two time periods, with
      voluntary hospitalizations overrepresented in 1981-1984 and civil commitments
      overrepresented in 1991-1994. The locus of hospitalization varied greatly between
      the two time periods. All hospitalizations in 1981-1984 took place in one of
      Oregon's three state hospitals. In 1991-1994, subjects were hospitalized in 13
      different institutions, including state and community hospitals and specially
      designed nonhospital inpatient facilities. CONCLUSIONS: Patterns of inpatient
      hospitalization for public psychiatric patients changed dramatically from 1981
      1984 to 1991-1994. The extensive use of community and nonhospital facilities
      raises questions about monitoring of quality of care in these diverse and
      decentralized facilities.

PMID- 9525799
TI  - Hospital utilization and personality characteristics of veterans with psychiatric
      problems.
AB  - OBJECTIVE: The relationship between hospital utilization and psychometric,
      demographic, and diagnostic data was examined among veterans with psychiatric
      problems. METHODS: Data were obtained from the records of 500 psychiatric
      inpatients admitted to a Veterans Affairs medical center between 1984 and 1987
      and followed for four years. All patients completed the Minnesota Multiphasic
      Personality Inventory, the California Personality Inventory, the Millon Clinical
      Multiaxial Inventory, and the Psychological Inventory of Personality and
      Symptoms. Stepwise linear regression analysis was used to predict the number and
      length of inpatient stays, and Cox and logistic regression analyses predicted
      rehospitalization. RESULTS: Higher rates of psychiatric hospital utilization were
      found among patients who were unmarried, who had disabilities connected with
      their military service, who had lower levels of adaptive functioning, and who
      were diagnosed as having posttraumatic stress disorder, drug or alcohol use
      disorder, or passive-aggressive or antisocial personality disorder. Higher
      utilization was also found among those whom psychometric data characterized as
      less responsible and more compulsive. The data also predicted the length of
      subsequent medical hospitalization and identified patients who stayed out of the
      hospital longer and who were not rehospitalized. CONCLUSIONS: Hospital
      utilization was found to be a function of psychiatric diagnosis, marital status,
      and various personality factors. Factors relating to social disadvantage also
      played a role. Axis I diagnoses, particularly substance use disorders, were as
      important as, if not more important than, axis II diagnoses in predicting
      utilization.

PMID- 9525800
TI  - Recognition of warning signs: a consideration for cost-effective treatment of
      severe mental illness.
AB  - Warning signs of decompensation, also known as prodromal symptoms, and problems
      related to poor recognition of warning signs were examined in a sample of 370
      adult outpatients with severe mental illness. Clinicians' ratings, client
      interviews, and eight months of client service records revealed that poor
      recognition of warning signs was a prevalent problem in this population and was
      related to poorer treatment outcomes and greater use of the most expensive types
      of services. Poor recognition was more likely to improve when it was specifically
      treated than when not treated. Improvement in recognition was related to better
      outcomes and lower costs. Results suggest the need for patients' recognition of
      warning signs to receive standardized assessment, treatment, and monitoring.

PMID- 9525801
TI  - Global functioning of inpatients with obsessive-compulsive disorder,
      schizophrenia, and major depression.
AB  - A chart review was conducted to compare the social, occupational, and daily
      functioning of 17 inpatients with obsessive-compulsive disorder, 17 with major
      depression, and 17 with schizophrenia. Current Global Assessment of Functioning
      (GAF) scores of patients with schizophrenia were significantly lower than those
      of patients with depression and with obsessive-compulsive disorder. However, on
      work performance, daily living skills, and past-year GAF scores, patients with
      obsessive-compulsive disorder and those with schizophrenia did not differ
      significantly, and both groups were significantly more impaired than patients
      with depression. Results show that inpatients with obsessive-compulsive disorder
      may exhibit severe and chronic functional impairments requiring extensive
      supportive and rehabilitative services.

PMID- 9525802
TI  - A survey of sexual trauma treatment provided by VA medical centers.
AB  - In 1992 Congress mandated the Department of Veterans Affairs to provide treatment
      to veterans traumatized by sexual assault experienced during active military
      duty. A 1995 survey of how VA medical centers had responded to this mandate
      indicated that 51 percent of 136 centers had established a sexual trauma
      treatment team. Teams treated a mean+/-SD of 5.5+/-10 patients a week, and newly
      referred veterans waited a mean of 3.3+/-4 days for evaluation. Teams varied in
      the discipline mix of providers, training, organizational structure, services
      offered, and caseload. Medical centers without dedicated treatment teams offered
      nonspecialized services to sexually traumatized veterans or offered community
      referrals for sexual trauma treatment services.

PMID- 9525804
TI  - Violent behavior.

PMID- 9525803
TI  - Improved diagnostic assessment of major depression in psychiatric outpatient care
      in Finland.
AB  - The accuracy of diagnosis of major depression by psychiatrists, psychiatric
      residents, and other physicians in outpatient psychiatric care settings in
      Finland was examined. A total of 232 patients who visited four mental health
      centers in the hospital district of Satakunta during three years (1989, 1992, and
      1995) were retrospectively given a diagnosis of first-episode major depression by
      researchers, based on chart reviews. These diagnoses were compared with those
      made by the evaluating clinicians. Accurate diagnosis was associated with the
      specialty of the physician and the location of the mental health center.
      Recognition of major depression significantly improved over the time period,
      which could be attributed to educational efforts, increasing familiarity with DSM
      III-R criteria, and use of new antidepressants.

PMID- 9525805
TI  - ADHD in adults.

PMID- 9525806
TI  - Alzheimer's disease and depression.

PMID- 9525807
TI  - President's 1999 budget seeks funding increases in most areas except mental
      health service programs.

PMID- 9525808
TI  - Drug-related episodes in psychiatric emergency services dropped 6 percent in
      1996, survey shows.

PMID- 9525809
TI  - Most court decisions support broad access to housing by disabled.

PMID- 9525811
TI  - Effects of DFMO on glioma cell proliferation, migration and invasion in vitro.
AB  - The polyamine inhibitor DL-alpha-difluoromethylornithine (DFMO) is a specific
      irreversible inhibitor of ornithine decarboxylase which is a rate-limiting enzyme
      in the polyamine bio-synthesis pathway. The present study describes the effects
      of DFMO on glioma cell proliferation, migration and invasion using multicellular
      spheroids from three glioma cell lines (GaMg, U-251 Mg and U-87 Mg). 10 mM DFMO
      reduced cell migration in the three cell lines by about 30-50%. 1 mM putrescine,
      added together with DFMO inhibited the DFMO effect. A stronger effect was
      observed in the growth assay where 10 mM DFMO reduced the spheroid growth, for
      all cell lines, by 90%. This effect was also reversed by adding 1 mM of
      putrescine. In vitro tumor cell invasion experiments indicated after 3 days of
      confrontation, an extensive invasion also after 10 mM DFMO treatment. The brain
      aggregate volumes were reduced to about the same extent as in the absence of
      drug, suggesting essentially no effects of DFMO on the invasive process. It is
      concluded that the tumor spheroids retained their ability to invade normal brain
      tissue even after DFMO exposure. However, DFMO inhibited spheroid growth and cell
      migration which supports the notion that cell growth, migration and invasion are
      biological properties that are not necessarily related to each other.

PMID- 9525810
TI  - Drug resistance and apoptosis in ENU-induced rat brain tumors treated with anti
      cancer drugs.
AB  - To cast light on the mechanisms of drug-resistance, experimental brain tumors
      were immunohistochemically evaluated for expression of glutathione S-transferase
      (GST)-alpha, mu, pi, p-glycoprotein and apoptosis-related factors, such as bcl-2
      and p53, as well as by the terminal deoxynucleotidyl transferase-mediated dUTP
      biotin nick end labelling (TUNEL) method. Rat brain tumors induced by means of
      prenatal exposure to ethylnitrosourea (ENU) were treated with 1-(4-amino-2-methyl
      5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU) and/or
      vincristine. Tumors more than 2 mm in size were considered to be drug resistant.
      The expression of GST-mu was strongly positive in ACNU-treated brain tumors,
      while p-glycoprotein was overexpressed in vincristine-treated brain tumors.
      Neither p53 nor bcl-2 expression directly correlated with apoptosis identified by
      TUNEL method, but tumors lacking apoptotic cells always demonstrated the
      expression of either GST-mu or p-glycoprotein. These results indicate that tumors
      resistant to chemotherapy might not be susceptible to induction of apoptosis, and
      therefore that mechanisms of drug resistance are related to programmed cell death
      in brain tumors.

PMID- 9525813
TI  - Genomic changes in glioblastoma cell lines detected by comparative genomic
      hybridization.
AB  - Comparative genomic hybridization serves as a screening test for regions of copy
      number changes in tumor genomes. We have applied the technique to map DNA gains
      and losses in 5 cell lines derived from glioblastoma multiforme, the most common
      primary neoplasm of the central nervous system. The most frequent losses occurred
      on chromosomes 10 and 13. The most common gains were observed on chromosomes 5,
      6, 7 and 20. Some novel sites of genomic alterations were also observed. Analysis
      of common areas of loss and gain in these cell lines provides a basis for future
      attempts to more finely map these genetic changes and for elucidation of genes
      involved in tumor progression.

PMID- 9525814
TI  - Mechanism of action of lonidamine in the 9L brain tumor model involves inhibition
      of lactate efflux and intracellular acidification.
AB  - Malignant gliomas have been associated with a high rate of glycolytic activity
      which is believed necessary to sustain cellular function and integrity. Since
      lonidamine (LND) is believed to reduce tumor glucose utilization by inhibition of
      the mitochondrially-bound glycolytic enzyme hexokinase (HK), 31P magnetic
      resonance spectroscopy (MRS) was used to noninvasively follow the effects of LND
      on both tumor pH and the high-energy phosphate metabolites: ATP, phosphocreatine
      (PCr) and inorganic phosphate (Pi) in subcutaneous rat 9L gliosarcomas. 31P tumor
      spectra acquired in 5 min intervals pre- and post LND administration of 50 and
      100 mg/kg, i.p. revealed an acidotic pH shift of -0.25 and -0.45 pH units,
      respectively within 30 min post administration. The ATP/Pi ratio of 9L tumors
      decreased to 40% of control and Pi levels increased to 280% of control over a 3
      hr period. LND exerted no effect on tumor blood flow and mean arterial blood
      pressure. Brain and muscle metabolite levels and pH were also unaffected by LND.
      In vitro measurements of cultured 9L tumor cell intra- and extracellular lactate,
      pentose phosphate pathway (PPP) and hexokinase (HK) activities suggest that the
      mode of action of LND involves inhibition of lactate efflux and intracellular
      acidification. The selective reduction of tumor energy metabolites and pH by LND
      may be exploitable for sensitizing gliomas to radiation, chemotherapy or
      hyperthermia.

PMID- 9525812
TI  - The role of transforming growth factor beta in glioma progression.
AB  - This review examines the apparently paradoxical conversion of transforming growth
      factor beta's (TGFbeta) regulatory role as a growth inhibitor among normal glial
      cells to that of a progression factor among glioblastomas (GM). In vitro, TGFbeta
      functions as an autocrine growth inhibitor of near-diploid gliomas of any grade.
      In contrast, hyperdiploid glioblastoma multiforme (HD-GM) cultures proliferate in
      response to TGFbeta, which is mediated by induction of platelet-derived growth
      factor B chain (PDGF-BB). The dominant hypothesis of TGFbeta's pathogenetic
      association with malignant transformation has been predicated upon acquisition of
      resistance to its growth inhibitory effects. However, the lack of obvious
      correlation with TGFbeta receptor (TbetaR) expression (or loss) between the HD-GM
      and the TGFbeta-inhibited GM cultures suggests the existence of intrinsically
      opposed regulatory mechanisms influenced by TGFbeta. The mechanism of conversion
      might be explained either by the loss of a putative tumor suppressor gene (TSG)
      which mediates TGFbeta's inhibition of growth or by enhancement of an active
      oncogenic pathway among the HD-GM. The frequency of mutations within glioma
      associated TSG, such as TP53 and RB, suggests that defects in TGFbeta's
      inhibitory signaling pathway may have analogous effects in the progression to HD
      GM, and TGFbeta's conversion to a mitogen. Alternative sites of inactivation
      which might explain the loss of TGFbeta's inhibitory effect include inactivating
      mutation/loss of the TbetaR type II, alterations in post-receptor signal
      transmission or the cyclin/cyclin dependent kinase system which regulates the
      phosphorylation of pRB. Loss or inactivation of a glial TSG with a consequent
      failure of inhibition appears to allow TGFbeta's other constitutive effects, such
      as induction of c-sis, to become functionally dominant. Mechanistically,
      TGFbeta's conversion from autocrine inhibitor to mitogen promotes 'clonal
      dominance' by conferring a Darwinian advantage to the hyperdiploid subpopulations
      through qualitative and quantitative differences in its modulation of PDGF-A and
      c-sis, with concomitant paracrine inhibition of competing, near-diploid elements.

PMID- 9525815
TI  - Altered therapy schedules in postoperative treatment of patients with malignant
      gliomas. Twenty year experience of the Maria Sklodowska-Curie Memorial Center in
      Krakow, 1973-1993.
AB  - Results of altered therapy schedules obtained in postoperative treatment of 294
      patients with malignant gliomas over last 20 years are presented. During this
      period 135 patients received Conventional Irradiation and Chemotherapy (CICH), 61
      patients received Conventional Irradiation (CI), 59 patients received Split
      Course High Fractional Dose Irradiation (SCHFDI), and 39 patients received Twice
      a Day Accelerated Irradiation (TDAI). Actuarial survival rates at 2, 3 and 5
      years were 19%, 7%, 0% respectively for patients treated with CICH, and they were
      21%, 10%, 0% for CI group, 24%, 12%, 0% for SCHFDI option and 15%, 8%, 0% for
      TDAI schedule. According to the Cox proportional hazard model, only age was
      significant factor in prognosis.

PMID- 9525816
TI  - Intra-arterial administration of carboplatin and the blood brain barrier
      permeabilizing agent, RMP-7: a toxicologic evaluation in swine.
AB  - RMP-7 is a bradykinin B2 receptor agonist shown to permeabilize the blood-brain
      barrier, especially that associated with brain tumors, when administered via both
      intracarotid and intravenous routes. Both routes of administration are currently
      being tested in human trials in combination with the chemotherapeutic agent
      carboplatin as therapy for gliomas. As an essential prerequisite to the initial
      intracarotid clinical trials, the potential neurotoxicity of intra-arterial
      administration of RMP-7 (at a high or low dose), alone and in combination with
      carboplatin, was assessed in anesthetized Red Duroc swine. Five treatment groups
      were evaluated with each pig receiving a series of alternating, intra-arterial
      infusions of RMP-7 (or saline) followed by carboplatin (or saline), as follows:
      (1) vehicle control: saline/saline; (2) carboplatin only control:
      saline/carboplatin (50 mg total); (3) RMP-7 only control: RMP-7 (750
      ng/kg)/saline; (4) low dose combination: RMP-7 (75 ng/kg)/carboplatin (50 mg
      total); and (5) high dose combination: RMP-7 (750 ng/kg)/carboplatin (50 mg
      total). For each subject, one of the alternating dosing sequences (above) was
      repeated four times during a single dosing session which lasted approximately 40
      minutes. Assessments during the in-life phase of the study in the pre- and post
      treatment periods consisted of heart rate, arterial blood pressure (systolic,
      diastolic, and mean), blood gases, body weight, general clinical observations
      (including evaluation for neurological deficit) and clinical pathology (including
      a comprehensive battery of standard blood coagulation, hematological and serum
      chemistry tests). In addition, during the time of treatment, heart rate and
      arterial blood pressure were monitored. The animals were terminated two weeks
      after dosing and the brain and rete mirabile (distal to site of infusion) were
      evaluated for gross and histopathological abnormalities. The histopathology
      analysis included a reader-blinded analysis using low and high power light
      microscopic examination of both H&E and Kluver-Berrera stained sections through
      several key cortical and subcortical brain regions. Transient decreases in
      arterial blood pressure (mean of 10-25 mmHg) were observed in both groups
      receiving the high dose of RMP-7 (i.e., 750 ng/kg). No other side effects
      attributable to RMP-7 and/or carboplatin were observed, and clinical observations
      revealed no evidence of neurologic deficits. Post-mortem examination revealed no
      evidence of CNS or cerebral vascular pathology attributable to carboplatin and
      RMP-7. This study demonstrates that intracarotid administration of the maximum
      tolerated dose of RMP-7 (750 ng/kg) alone, or in combination with carboplatin (50
      mg) is not accompanied by any serious adverse effect, apparent cerebrovascular
      abnormality or neuropathologic consequence and offers further evidence for the
      safety of this novel therapeutic approach for enhancing delivery of
      chemotherapeutics to brain tumors.

PMID- 9525817
TI  - Unusual nasal and orbital involvement of glioblastoma multiforme: a case report
      and review of the literature.
AB  - We describe a case of glioblastoma treated with chemoradiotherapy that spread to
      the dura mater with direct invasion of the skull base, protrusion into the
      homolateral nasal fossa, and penetrated of the frontal sinus, the orbital wall
      and the ethmoidal sinuses. Only eight cases of glioblastoma showing this
      development have been described in the literature; one of these, however, had a
      sarcomatous component which was absent in our case.

PMID- 9525819
TI  - Phase II study of intracarotid or selective intracerebral infusion of cisplatin
      for treatment of recurrent anaplastic gliomas.
AB  - PURPOSE: To assess the response of patients with recurrent malignant gliomas to
      intra-arterial (IA) cisplatin. METHODS: Eligibility criteria included patients
      with recurrent supratentorial malignant gliomas and measurable, unilateral
      contrast-enhancing tumor located within the territory of one or two major
      cerebral arteries. Patients received 75 mg/m2 IA cisplatin every four weeks.
      Depending on individual patients' tumor topography, cisplatin was infused either
      into the cervical internal carotid artery (ICA) (15 patients), or into one or two
      major cerebral arteries (26 patients), most often the M1 segment of the middle
      cerebral artery. RESULTS: Of 40 patients evaluable for tumor response, four
      patients (10%) were responders and nine patients (22%) had disease stabilization.
      The median time to tumor progression among the 13 patients with tumor response or
      stable disease was 23.7 weeks. The response rate did not significantly differ
      between patients receiving ICA versus selective intracerebral infusion, although
      the latter group contained a higher proportion of glioblastoma. Tumor progression
      occurred solely as local failure in 33 patients (82%), with all enhancing tumor
      still located within the vascular territory infused with IA cisplatin.
      Ipsilateral vision loss occurred in two patients after ICA cisplatin but in none
      of the selective infusion patients. Seizures and/or transient or permanent
      neurologic deterioration occurred in four patients (27%) after ICA cisplatin and
      in 11 patients (44%) after selective intracerebral infusion. CONCLUSIONS:
      Although this was not a randomized comparison, selective intracerebral artery
      cisplatin infusion in this group of patients reduced the risk of eye toxicity,
      but did not produce a better tumor response rate, and carried a higher risk of
      neurotoxicity relative to ICA infusion.

PMID- 9525818
TI  - Chorea as a paraneoplastic complication of Hodgkin's disease.
AB  - Neurologic complications of Hodgkin's disease (HD) include both metastatic and
      non-metastatic involvement of the nervous system. There are at least five
      paraneoplastic syndromes associated with HD but chorea has not been described. We
      report the first choreiform disorder as a paraneoplastic complication of HD and
      only the second case of paraneoplastic chorea in the literature.

PMID- 9525820
TI  - Chemotherapy in experimental brain tumor, part 1: in vitro colorimetric MTT
      assay.
AB  - This study concerns the use of the MTT [3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl
      2H tetrazolium bromide] colorimetric assay to evaluate the chemosensitivity of
      the C6 rat glioma cell line to a panel of twelve chemotherapeutic agents. In a
      previous study of in vitro chemosensitivity of human glioma cell lines, the
      present authors found a range of sensitivities of the respective cell lines to a
      panel of chemotherapeutic agents [1]. We then devised an experimental strategy to
      begin an in vivo evaluation of the correlation between in vitro chemosensitivity
      and clinical response in an in vivo animal model, such as the model employing the
      C6 rat glioma cell line. As a step towards utilizing the C6 rat glioma in vivo
      model, we carried out the present study (Part 1) to determine the correspondence
      between chemosensitivity to human glioma cell lines and the rat C6 glioma cell
      line. If a correspondence were to be found, this would enable experimental use of
      the C6 tumor model for in vivo testing of chemotherapeutic agents. As reported in
      this paper (Part 1), a correspondence was found, suggesting that the C6 rat
      glioma represents a suitable model of human glioma for chemotherapeutic studies.
      This finding served as a basis for proceeding with an in vivo study of
      chemotherapeutic efficacy which is the subject of a companion report [2].

PMID- 9525821
TI  - Chemotherapy in experimental brain tumor, part 2: pretreatment with leukotriene
      C4 prolongs survival.
AB  - Previous work in our laboratory has shown a correspondence between the
      chemosensitivity of C6 rat glioma and that of human glioblastoma (GBM) to a panel
      of chemotherapeutic agents in vitro, as determined by the MTT [3-(4,5-dimethyl-2
      thiazolyl)-2,5-diphenyl-2H tetrazolium bromide] colorimetric assay. In the
      present study, an in vivo model of intracerebral C6 glioma in Sprague-Dawley rats
      was used to determine if a correlation exists between in vitro chemosensitivity
      and in vivo survival of the animals, and post-mortem histopathological changes in
      the tumor. Cisplatin (CDDP) and methotrexate (MTX), agents previously shown to
      demonstrate high and low in vitro cytotoxicity, respectively, against C6, were
      administered by intra-carotid infusion over the course of two days. In a separate
      series of animals, LTC4 was administered prior to infusion of CDDP or MTX; LTC4
      was used in view of its known, selective, vasogenic effect on the permeability of
      brain tumor capillaries. It was found that survival of animals treated with CDDP
      alone was increased, although this did not reach statistical significance;
      histopathologically, CDDP-treated animals showed significant tumor necrosis.
      However, in CDDP-treated animals, pre-treatment with LTC4 increased survival to a
      statistically significant degree. When administered alone, LTC4 (not followed by
      CDDP) had no effect on either survival or histology. The survival-enhancing
      effect of CDDP, when combined with LTC4, was probably not due to any cytotoxic
      effect of LTC4; this is based on our finding that, on the in vitro MTT
      colorimetric assay, LTC4 showed low cytotoxicity for C6 glioma cells. By contrast
      with CDDP, MTX -- with or without pretreatment with LTC4 -- affected neither
      survival nor tumor histology. With respect to the question of correspondence
      between the MTT colorimetric in vitro assay and in vivo effect, MTX showed a
      clear correlation: low cytotoxicity in vitro and poor in vivo response. In the
      case of CDDP, the correspondence was not clear-cut: there was a high level of in
      vitro chemosensitivity of the C6 cell line to CDDP as well as post-mortem tumor
      necrosis, but in vivo testing showed no significant prolongation of survival.
      However, pre-treatment with LTC4 did significantly extend survival in animals
      treated with CDDP.

PMID- 9525822
TI  - High levels of gelatinase-B and active gelatinase-A in metastatic glioblastoma.
AB  - PURPOSE: Extra-neural metastases from glioblastoma multiforme (GBM) are rare.
      Because gelatinases-A and -B have been implicated in tumor invasion/metastasis in
      non-neural tumors, we compared the expression of gelatinase-A and -B in 2
      patients (both had a prior craniotomy performed) with extraneural metastases from
      GBM to expression levels in 24 other gliomas; 15 non-metastatic GBMs, 9 other
      lower grade gliomas, and 7 normal brain tissues. METHODS: The intracerebral tumor
      from both patients, patient # 1's extraneural metastases, 24 other gliomas, 1
      sample of reactive astrocytes and 7 normal brain tissues were studied using
      gelatin zymography. The active form of gelatinases was confirmed by co-migration
      after activation with APMA. RESULTS: Expression of the latent form of gelatinase
      A correlated with glioma grade (r = 0.486; p = 0.0053). Active gelatinase-A was
      found only in the 2 GBMs with extraneural metastases and patient # 1's cervical
      metastases. In contrast, latent gelatinase-B levels correlated more strongly with
      histologic grade (r = 0.577; p = 0.0009) (higher levels with higher grades). Very
      high levels of gelatinase-B were seen in both GBMs with extraneural metastases, a
      cervical extraneural metastases, and 2 GBMs without metastases. CONCLUSIONS: We
      observed that gelatinases-A and -B are present in most gliomas but we found
      active gelatinase-A only in the GBMs with extraneural metastases suggesting that
      the active form of this enzyme may determine the metastatic potential of GBMs. We
      propose that high levels of gelatinolytic activities are associated with
      intracerebral invasion and rarely, metastases of GBMs.

PMID- 9525825
TI  - Leptomeningeal metastases: evaluation by gadolinium enhanced spinal magnetic
      resonance imaging.
AB  - BACKGROUND: Leptomeningeal metastases are common in patients with metastatic
      systemic cancer or certain primary brain tumors. They may be unsuspected
      clinically and may be missed by cerebrospinal fluid (CSF) cytology. We undertook
      a retrospective study of the diagnostic value of gadolinium enhanced spinal MR
      imaging in patients with known or at high risk for leptomeningeal metastases
      (LM). MATERIAL AND METHODS: Ninety-six gadolinium enhanced MR examinations of the
      whole spine were performed in 61 patients (26 primary central nervous system
      tumors, 20 solid tumors and 15 lymphoproliferative neoplasms). All patients had
      detailed neurological evaluation and concomitant CSF examination. RESULTS: Sixty
      one MR's (62%) were positive, mostly in the lumbar spine. MR's were positive in
      92% of patients with positive initial CSF cytology and in 60% of patients with
      negative CSF cytology. The MR examination was positive in 49% of those without
      clinical findings related to the spinal region. It showed disease beyond the
      symptomatic level in 42% of patients with spinal symptomatology. Multi-level
      spinal involvement was present in 57% of positive MR exams. CONCLUSION: Enhanced
      spinal MR is sensitive for the detection of neoplastic spinal seeding. It detects
      LM in about 50% of high risk patients with negative initial CSF cytology or no
      spinal symptoms.

PMID- 9525826
TI  - Long-term survival in patients with supratentorial glioblastoma.
AB  - The authors report 11 patients with cerebral glioblastoma who lived at least 5
      years after their initial diagnosis. There were 6 female and 5 male; the mean age
      was 39 years (range 24-55 years). All patients were treated surgically and
      postoperatively received whole-brain radiotherapy and chemotherapy. Five patients
      (45%) presented local recurrences after an average interval of 3.9 years from
      treatment. At average follow-up of 9 years (range 5-14 years), 7 patients (64%)
      were alive after an average interval of 8.1 years; 4 patients (36%) died from
      local relapse. Survival was influenced by patient age and, to a lesser degree, by
      treatment. A review of the literature, together with our own series, suggest that
      death from recurrence disease is unusual in glioblastoma patients who survive
      more than 5 years.

PMID- 9525824
TI  - In vivo etoposide-resistant C6 glioma cell line: significance of altered DNA
      topoisomerase II activity in multi-drug resistance.
AB  - We have established an in vivo etoposide-resistant glioma cell line (C6/VP) from
      C6 rat glioma cells by stepwise exposure to increasing doses of etoposide. The
      C6/VP cells were 10 times more resistant to etoposide than the parental C6 cells.
      In addition C6/VP cells demonstrated cross-resistance to vincristine and
      vinblastine, but not to ADM or m-AMSA. Interestingly, the cells had collateral
      sensitivity to ACNU, cisDDP and Ara-C. The C6/VP cells did not express the MDR
      gene or p-glycoprotein, while they showed 16 times less topoisomerase II
      catalytic activity compared to the C6 cells. Although there was no significant
      difference between C6 and C6/VP cells in amounts of topoisomerase II in nuclear
      extracts, the C6/VP cells had 2.9 times higher amounts of the enzyme than C6
      cells in nuclear scaffold prepared from a relatively low-salt buffer (0.5 M
      NaCl). Northern blot analysis demonstrated that mRNAs of topoisomerase IIalpha
      isoforms were expressed both in C6 and C6/VP cells, and that the amounts of
      topoisomerase IIalpha in C6/VP cells were 14 times greater than in C6 cells. The
      total uptake of etoposide in tumor tissues derived from C6/VP cells was 3 times
      less than those derived from parental C6 cells. These results indicate that the
      C6/VP acquired a multi-drug resistance phenotype by a reduction of the catalytic
      activity of topoisomerase II and/or diminished accumulation of drugs. This
      phenotype did not involve the p-glycoprotein. Alterations of topoisomerase II in
      the C6/VP cells also were accompanied by an increased amount of the topoisomerase
      IIalpha isoform, most of which was localized in the nuclear scaffold (matrix).
      This suggests that altered binding of topoisomerase II to topologically organized
      DNAs in the nuclear scaffold may be the molecular basis of this multi-drug
      resistance phenotype.

PMID- 9525823
TI  - Experimental cisplatin neuronopathy in rats and the effect of retinoic acid
      administration.
AB  - Peripheral nervous system alterations were induced in adult rats by
      administration of cisplatin (CDDP) 2 mg/kg twice weekly for 4.5 weeks. Dorsal
      root ganglion neurons showed pathological changes. Morphometric determinations
      demonstrated a reduction in size of the somatic, nuclear and nucleolar area. The
      nucleoli were the most involved subcellular structures. Nerve conduction velocity
      and the tail-flick test for pain were both significantly altered in CDDP treated
      rats, whereas the rota-rod test for coordination revealed no changes in either
      treated or control rats. Analytical determinations demonstrated platinum
      accumulation in the DRG of CDDP treated rats. Spontaneous recovery, demonstrated
      by morphometric, electrophysiological, functional and analytical determinations,
      occurred after treatment discontinuation within about 7 weeks. A pilot study of
      the possible neuroprotective action of retinoic acid (RA) was also performed with
      this model of cisplatin neuronopathy. The rationale for using RA was based on its
      assumed antioxidant and neurotrophic effect. However, RA failed to prevent
      morphometric, electrophysiological, functional and analytical alterations induced
      by CDDP on DRG neurons. RA induced only a mild generalized protective effect.

PMID- 9525827
TI  - Phase II trial of recombinant interferon-alpha-2a and eflornithine in patients
      with recurrent glioma.
AB  - Interferons alpha and beta have been reported to cause tumor regression in a
      small proportion of patients with recurrent glioma. Eflornithine, an irreversible
      inhibitor of ornithine decarboxylase, reduces cellular polyamine levels and has
      also been reported to cause tumor regression in patients with recurrent
      anaplastic astrocytoma and glioblastoma multiforme. In vitro evidence suggests
      that interferon and eflornithine are synergistic. In this phase II trial, we
      investigated the combination of recombinant alpha interferon (36 x 10(6) units/m2
      subcutaneously days 3 to 7) and eflornithine (2.25 g/m2 QID PO days 1 to 7)
      repeated every 28 days. All 29 patients entered in the study were evaluable for
      toxicity and efficacy. Toxicity consisted primarily of fever, chills, myalgia,
      weakness and fatigue as well as cortical dysfunction including somnolence,
      confusion, and exacerbation of underlying neurologic deficits. One patient died
      from cerebral herniation attributable to interferon. None of the patients
      experienced objective tumor regression. Seven patients (24%) were stable for more
      than six months, but the disease stability could also be explained by indolent
      underlying disease or inability to distinguish recurrent tumor from delayed
      radiation effects. Intermittent high-dose recombinant interferon alpha plus
      eflornithine demonstrated no definite antitumor effects in this trial.

PMID- 9525828
TI  - The prognostic factors of lung cancer patients with brain metastases treated with
      radiotherapy.
AB  - PURPOSE: To analyze the prognostic factors of lung cancer with brain metastases
      (BM) and evaluate the role of cranial irradiation on survival. METHODS AND
      MATERIALS: From 1987 to 1994, 159 lung cancer patients with CT scan documented BM
      were reviewed. All of them underwent cranial irradiation (median radiation dose:
      30 Gy). Chemotherapy and surgery of BM were performed in 21 and 10 cases,
      respectively. RESULTS: Overall median survival was 3.5 months and one year
      survival rate was 10.69%. Univariate analysis showed that the significant factors
      were performance status, age, total radiation dose to brain, BM as the first
      metastasis, neurosurgery, symptoms of urine/stool incontinence, and synchronous
      BM. Multivariate analysis indicated that (1) performance status (p = 0.0002), (2)
      total radiation dose (p = 0.0032), (3) BM as the first metastasis (p = 0.0449),
      (4) neurosurgery (p = 0.0233), (5) symptoms of urine/stool incontinence (p =
      0.0002), and (6) the presence of a midline shift on cranial CT scans (p = 0.0063)
      were significant prognostic factors. CONCLUSION: The prognosis of BM in lung
      cancer patients is extremely poor. Radiotherapy appears as an effective means of
      palliation with 75% overall symptomatic response rate. Higher radiation dose (>
      or = 30 Gy) and neurosurgery are associated with longer survival. Good
      performance status, BM as the first metastasis, absence of sphincter dysfunction,
      and midline shift on CT scans are favorable prognostic predictors. The role of
      midline shift is very interesting and needs to be explored further.

PMID- 9525829
TI  - Primary intramedullary spinal melanoma: diagnostic and treatment problems.
AB  - A 76-year old female patient with 9 year history of right mastectomy for an
      infiltrating ductal breast cancer and no evidence of recurrent nor metastatic
      disease, was admitted due to pain in the lower thoracic area radiating
      bilaterally to the posterior aspect of the chest wall at the same level,
      difficulties in micturition, urinary hesitancy, and progressive weakness of the
      lower limbs. Primary intramedullary spinal tumor was demonstrated by a MRI study
      of the spine, partially resected, and found to be a malignant melanoma on
      pathological study. Postoperative irradiation and administration of dexamethasone
      did not improve the neurologic status.

PMID- 9525830
TI  - Nervous system involvement by metastatic hepatocellular carcinoma.
AB  - Nineteen patients with nervous system metastasis of hepatocellular carcinoma
      (HCC) were evaluated retrospectively. Nervous system metastasis was frequently
      initial presentation of HCC (seven out of 19 patients). Seven patients had
      metastases of the brain, of whom four had a stroke-like presentation. CT or MRI
      in these patients showed intracerebral hematomas in watershed areas. Enhancing
      lesion or edema adjacent to the hematoma helped differentiate these lesions from
      classical hypertensive hematomas. One patient with metastasis to the clivus
      presented with isolated six nerve palsy. The remaining 11 patients had spinal
      epidural metastases producing myelopathy in seven and radiculopathy in four.
      Radiation therapy failed to control the clinical course.

PMID- 9525832
TI  - The effect of dexamethasone on the uptake of cisplatin in 9L glioma and the area
      of brain around tumor.
AB  - The negative influence of dexamethasone (Dex) on the uptake of cisplatin in brain
      tumors was investigated in rats bearing 9L glioma. Dex or saline was given
      intraperitoneally prior to intravenous administration of cisplatin 5 mg/kg. Total
      Platinum (Pt) concentration was quantified with atomic absorption spectroscopy
      (AAS) in tumor, brain around tumor (BAT), normal brain and plasma. In the second
      experiment DNA-adducts of cisplatin were determined in tumor and BAT by AAS. In
      tumor, there was no difference in the Pt concentration and in the DNA-adduct
      level between the two treatment groups. In BAT, the Pt level in the Dex group was
      0.20 microg/g (SD=0.10 microg/g), which was significantly lower than in the
      controls (0.53 microg/g (SD=0.21 microg/g); p < 0.001). In addition, the DNA
      adduct level in BAT was 23% lower in the Dex treated rats (p=0.05). In normal
      brain the Pt concentration was 10-fold lower than in tumor tissue. Thus, Dex did
      not significantly limit the uptake of cisplatin in brain tumor nor did it
      influence the uptake in normal brain parenchyma. In contrast, in BAT that has a
      partially disrupted BBB, the concentrations of Pt and DNA-adduct formation were
      significantly decreased following pretreatment with Dex. The influence of Dex on
      limiting the effects of chemotherapy for brain tumors needs further study.

PMID- 9525833
TI  - The proliferative potential of the pilocytic astrocytoma: the relation between
      MIB-1 labeling and clinical and neuro-radiological follow-up.
AB  - The proliferative potential of 39 pilocytic and 5 low grade astrocytomas was
      studied in relation to the Ki-67 activity as measured by the MIB-1 Labelings
      Index. The results were correlated to the biological behaviour of the tumor as
      measured by clinical and neuro-radiological (CT- or MRI-scans) follow-up of the
      patient. This study was undertaken to answer the question whether MIB-1
      expression reflects differences in biological behaviour of these tumors, such as
      rapid progression of residual tumor or stable remaining tumor. MIB-1 LI values
      ranged from 0 to 19% in the group of pilocytic astrocytomas (mean 4.2%) and from
      0 to 15% in the 5 low grade astrocytomas (mean 4,2%). All patients were operated
      and 23 of them had incomplete tumor resection as proven on postoperative neuro
      imaging studies. Those 23 patients could be subdivided into two groups; one
      without progression of residual tumor during follow-up (n=12) and the other with
      tumor progression (n=11). mean MIB-1 LI in the group with 'quiescent' tumor
      tended to be lower than in the group with progressive tumor: 3,3% vs. 6,6%.
      Residual tumors which were negative for MIB-1 staining showed fewer progressions
      of residual tumor compared to those being positive for MIB-1 staining, however
      this difference was not significant (p=0, 15, Fisher exact test). Tumor samples
      of a second operation of the same patient had lower MIB-1 LI values than those of
      the samples taken at first operation. The proliferating potential seemed to be
      decreased after part of the tumor was resected. Pilocytic astrocytomas with a
      negative MIB-1 LI are unlikely to show progression of residual tumor after
      partial resection. MIB-1 staining might be an additional tool in determining the
      frequency and duration of follow-up and in making decisions regarding further
      treatment of a patient operated for a pilocytic astrocytoma with residual tumor.

PMID- 9525831
TI  - Rat brain tumor models in experimental neuro-oncology: the 9L, C6, T9, F98, RG2
      (D74), RT-2 and CNS-1 gliomas.
AB  - Rat brain tumor models have been widely used in experimental neuro-oncology for
      almost three decades. The present review, which will be selective rather than
      comprehensive, will focus entirely on seven rat brain tumor models and their
      utility in evaluating the efficacy of various therapeutic modalities. Although no
      currently available animal brain tumor model exactly simulates human high grade
      brain tumors, the rat models that are currently available have provided a wealth
      of information on in vitro and in vivo biochemical and biological properties of
      brain tumors and their in vivo responses to various therapeutic modalities.
      Ideally, valid brain tumor models should be derived from glial cells, grow in
      vitro and in vivo with predictable and reproducible growth patterns that simulate
      human gliomas, be weakly or non-immunogenic, and their response to therapy, or
      lack thereof, should resemble human brain tumors. The following tumors will be
      discussed. The 9L gliosarcoma, which was chemically induced in an inbred Fischer
      rat, has been one of the most widely used of all rat brain tumor models and has
      provided much useful information relating to brain tumor biology and therapy. The
      T9 glioma, although generally unrecognized, was and probably still is the same as
      the 9L. Both of these tumors can be immunogenic under the appropriate
      circumstances, and this must be taken into consideration when using either of
      them for studies of therapeutic efficacy, especially if survival is used as an
      endpoint. The C6 glioma, which was chemically induced in an outbred Wistar rat,
      has been extensively used for a variety of studies, but is not syngeneic to any
      inbred strain. Its potential to evoke an alloimmune response is a serious
      limitation, if it is being used in survival studies. The F98 and RG2 (D74)
      gliomas were both chemically induced tumors that appear to be either weakly or
      non-immunogenic. These tumors have been refractory to a variety of therapeutic
      modalities and their invasive pattern of growth and uniform lethality following
      an innoculum of as few as 10 tumor cells make them particularly attractive models
      to test new therapeutic modalities. The Avian Sarcoma Virus induced tumors and a
      continuous cell line derived from one of them, designated RT-2, have been useful
      for studies in which de novo tumor induction is an important requirement. These
      tumors, however, are immunogenic and this may limit their usefulness for survival
      studies. Finally, a new chemically induced tumor recently has been described, the
      CNS-1, and it appears to have a number of properties that should make it useful
      in experimental neuro-oncology. It is essential to recognize, however, the
      limitations of each of the models that have been described, and depending upon
      the nature of the study to be conducted, it is important that the appropriate
      model be selected.

PMID- 9525834
TI  - Human astrocytoma cells are capable of producing macrophage inflammatory protein
      1beta.
AB  - We investigated expression of macrophage inflammatory protein-1 (MIP-1) alpha and
      beta in human astrocytoma cell lines and surgical specimens of astrocytic tumors.
      Enzyme-linked immunosorbent assay (ELISA) showed constitutive secretion of MIP
      1alpha protein in only one and MIP-1beta in none of 7 cell lines tested. However,
      MIP-1alpha production was increased in three cell lines by stimulation with
      lipopolysaccharide (LPS) and 5 cell lines by stimulation with phorbol-12myristate
      13-acetate (PMA). Also, induction of MIP-1beta production was observed in one
      cell line with LPS stimulation and in two cell lines with PMA stimulation.
      Reverse-transcription polymerase chain reaction (RT-PCR) showed the increase of
      MIP-1alpha and beta mRNA expression in these cell lines. The increase of the mRNA
      with the stimuli was further confirmed by Northern blot analysis. In contrast, RT
      PCR analysis revealed that the majority of the tested tumor specimens of high
      grade.astrocytomas expressed both MIP-1alpha and MIP-1beta mRNAs. ELISA detected
      MIP-1beta protein in 1 of 11 cerebrospinal fluid samples from patients with high
      grade astrocytoma and in 8 of 9 tumor cyst fluid samples, whereas MIP-1alpha was
      detected in only 1 cyst fluid somple. Taken together, these results indicate that
      astrocytic tumor cells are capable of expressing and producing MIPs, and suggest
      that MIPs may participate in the inflammatory responses commonly seen in
      astrocytic tumors.

PMID- 9525835
TI  - Molecular cytogenetic studies of pediatric ependymomas.
AB  - Cytogenetic and molecular studies of ependymomas have previously demonstrated
      deletions of chromosomes 17 and 22 as frequent abnormalities, implicating
      inactivation of tumor suppressor genes in the pathogenesis of these tumors. In
      the present study, we analyzed 22 childhood ependymomas by standard cytogenetic
      analysis, fluorescence in situ hybridization (FISH) and polymerase chain reaction
      (PCR)-based microsatellite analysis of chromosomes 17 and 22. Microsatellite
      analysis of chromosome 6 was performed to identify submicroscopic deletions
      implicated by the cytogenetic studies. Among the 22 cases, we demonstrated loss
      of chromosome 22 in 2 patients, deletion of chromosome 17 in 2 patients, and
      rearrangements or deletions of chromosome 6 in 5 patients. These data do not
      suggest that loss of a gene on chromosome 17p plays a primary role in the
      initiation of pediatric ependymomas. This is in contrast to what has been
      reported for pediatric CNS primitive neuroectodermal tumors and malignant
      astrocytomas, in which deletion of 17p is regarded as a primary event.
      Furthermore, loss of chromosome 22 may define a subset of ependymomas more
      commonly seen in adults. Cytogenetic studies in this series, however, suggest
      that a region on the long arm of chromosome may be involved in the development
      and/or progression of ependymomas in children.

PMID- 9525836
TI  - Glial tumoral proliferation induces changes in the state and physical properties
      of water during ENU-induction of brain tumors in rats.
AB  - Modifications of water state were analyzed during ethylnitrosourea-induction of
      brain tumor in rats. Four different steps were identified in the cancerization
      process according to NMR and histological findings. Two analogies were observed
      in the pattern of bound' water at decreasing temperatures: first the pattern was
      similar in tumor area and white matter, second the pattern was similar in the
      same area of normal brain tissue and cortical gray matter. This phenomenon, which
      corroborates previous reports on liver cancerization, points out that
      pathological proliferation of glial cells, and their progressive organization
      into multiple layers, is accompanied by a transformation of water properties at
      the cellular level.

PMID- 9525838
TI  - A therapeutic trial of radiation therapy with Vincristine, etoposide, and
      Procarbazine (VVP) in high grade intracranial gliomas--an Eastern Cooperative
      Oncology Group Study (E2392).
AB  - This study is a combined modality Phase II therapeutic trial to determine the
      efficacy of the novel combination of VP-16, Vincristine and Procarbazine in
      addition to postoperative radiation therapy in patients with high grade
      intracranial gliomas. Thirty three patients (median age 51 years) were entered
      (27 with glioblastoma multiforme, 6 with anaplastic astrocytoma). Toxicity was
      manageable with no lethal toxicities. Five of seven life threatening toxicities
      were hematologic. Median overall survival was 14.2 months. These data suggest
      this regimen is effective treatment for patients with high grade gliomas.

PMID- 9525839
TI  - Paraneoplastic limbic encephalitis with immature ovarian teratoma--a case report.
AB  - Paraneoplastic limbic encephalitis (PLE) is a remote, nonmetastatic complication
      of carcinoma. Neuropsychiatric symptoms usually predate the diagnosis of cancer
      by 3 months to 6 years and very rarely the symptoms develop after the diagnosis
      of malignancy. We report the first case of limbic encephalitis associated with an
      immature ovarian teratoma. Within the month following the diagnosis of the tumor
      with pathologic stage Ia, somewhat acutely she developed neuropsychiatric
      symptoms that was exclusively a limbic disorder with impairments in almost every
      realm of limbic function. This case may show us that it is important to recognize
      the neuropsychiatric symptoms of PLE as the first manifestation of a very small
      malignant ovarian tumor and to aggressively try to identify the underlying
      cancer.

PMID- 9525837
TI  - Modulation of doxorubicin concentration by cyclosporin A in brain and testicular
      barrier tissues expressing P-glycoprotein in rats.
AB  - P-glycoprotein (Pgp) is an inducible transmembrane protein that functions as an
      ATP-dependent efflux pump. Pgp is normally expressed in two types of cells:
      specialized epithelial cells with secretory/excretory functions (e.g., proximal
      renal tubules) and specialized endothelial cells (e.g., the capillary endothelial
      cells of the blood-brain barrier). In normal tissues, Pgp could exert a
      cytoprotective effect by facilitating excretion of drugs. It follows that
      inhibition of Pgp would alter the pharmacokinetics of drugs, like doxorubicin, in
      cells that express Pgp. The purpose of this study was to determine whether or not
      inhibition of Pgp by cyclosporin A (CsA) facilitated the transport of certain
      drugs across the blood tissue barriers of the brain and testes (barriers tissues
      expressing Pgp). 120 retired male breeder CD Fisher rats were randomly assigned
      to groups of 4 rats each. They were given either CsA, CsA vehicle, or saline
      followed by doxorubicin (Dox), cisplatin (CDDP), Evan's blue (EB), sodium
      fluorescein (NaF), or horseradish peroxidase (HRP). There was a CsA dose
      dependent increase in the tissue concentration of doxorubicin in brain and
      testes, but platinum (Pt) concentrations, derived from CDDP, were unaffected.
      Unlike CDDP, Dox, can be effluxed by Pgp. These increases in Dox concentrations
      were not due to altered vascular permeability as a result of CsA treatment as
      determined by lack of EB. NaF, or HRP in brain parenchyma. Modulation of Pgp
      function may prove to be useful for improving chemotherapy efficacy for patients
      with malignancies affecting tissues with blood-tissue barriers.

PMID- 9525840
TI  - High dose chemotherapy with autologous bone marrow rescue for children with
      diffuse pontine brain stem tumors. Children's Cancer Group.
AB  - PURPOSE: Diffuse pontine tumors are highly lethal, and there are few long-term
      survivors with the standard treatment of external beam irradiation. We
      investigated the effectiveness of high-dose thiotepa and etoposide-based
      chemotherapy regimens with autologous bone marrow rescue (ABMR) in children with
      pontine tumors. PATIENTS AND METHODS: Sixteen children with diffuse pontine
      tumors were treated. Ten had resistant or recurrent tumors. All ten had
      previously received irradiation; five had also received chemotherapy and one,
      beta-interferon. Three high-dose chemotherapy regimens were employed. Six
      patients received three days of thiotepa (300 mg/m2/day) and etoposide (250-500
      mg/m2/day) (TE); two received three days of carmustine (BCNU) (200 mg/m2/day
      divided every 12 hours) followed by TE (BTE); and two received three days of
      carboplatin (500 mg/m2/day) followed by TE (CTE). Six other patients had newly
      diagnosed tumors and had not received any prior treatment. They all received the
      BTE regimen and subsequently were treated with hyperfractionated irradiation
      (7200-7800 cGy) beginning approximately six weeks post-ABMR. RESULTS: There were
      two toxic deaths (13%), both in previously treated patients, due to multiorgan
      system failure and Candida septicemia in one case each. Median survival of the
      patients with resistant or recurrent disease was 4.7 months (range 0.1-18.7) from
      time of ABMR. Median survival of the newly-diagnosed patients was 11.4 months
      (range 7.6-17.1) from the time of ABMR. CONCLUSION: High-dose chemotherapy
      utilizing these regimens followed by ABMR did not appear to prolong survival
      compared to conventional therapy in these children with pontine tumors.
      Alternative strategies need to be developed for this highly lethal disease.

PMID- 9525841
TI  - Intracranial germinoma: treatment with radiosurgery alone--a case report.
AB  - The management of intracranial germinomas is controversial, with treatment
      options including conventional wide-field irradiation with or without
      chemotherapy or primary chemotherapy alone. The potential role of radiosurgery in
      the treatment of these lesions, although appealing, remains to be defined. We
      report a case whose initial management plan included radiosurgery to be followed
      by chemotherapy; however the patient subsequently refused chemotherapy. The
      presentation, diagnosis, treatment and results are discussed.

PMID- 9525843
TI  - Volumetric measurement of brain tumors from MR imaging.
AB  - Residual tumor volume has been considered important in predicting survival
      following brain surgery. The purpose of this study was to develop a procedure for
      quantifying pre- and postsurgical brain tumor volumes that is less subjective
      than the traditional qualitative grading scale still used by surgeons and
      radiologists to assess extent of resection (such as gross total, subtotal, and
      partial resection). Pre- and postsurgical magnetic resonance (MR) imaging brain
      scans on GE Medical System optical disks were transferred to a Macintosh personal
      computer using a Pioneer optical disk drive subsystem, and the MedVision 1.41
      computer software program was used to analyze regions of interest (ROIs) within
      them for computation of the volume of tumor tissue therein. Because this
      procedure puts the original MRI (or CT scan) data file for a patient directly
      into the personal computer, it bypasses the need for scanning and digitizing MR
      (or CT scan) film images. Between June 1993 and May 1996, pre- and postsurgical
      volumetric measurements were made in more than 1,000 brain tumor resection cases
      and 49 radiosurgery cases. The average intra-observer error was estimated to be
      1.8%. This method should facilitate the examination of the effects of various
      therapies on extent of brain tumor resection. The method is fast, is more precise
      than intraoperative visual assessment of tumor removal or qualitative comparison
      of pre- and postoperative scans, and it allows the computation of pre- and
      postsurgical (three-dimensional) volumes of even irregularly shaped tumors.

PMID- 9525842
TI  - Stereotactic radiosurgery for brain metastases: comparison of lung carcinoma vs.
      non-lung tumors.
AB  - In the medical literature, stereotactic radiosurgery (SRS) for brain metastases
      results in rates of local control of 65 to 85 %. To define patient selection
      criteria, we measured the survival in a population with a high proportion of non
      small cell lung carcinoma (NCS lung) metastases that occurred soon after primary
      diagnosis. Between 9/89 and 10/93 30 adults (21 M, 9 F) had SRS for metastatic
      NSC lung carcinoma (14 patients) vs. non-lung carcinomas (16 patients having
      breast (3), renal (3), melanoma (3), GI (2, thyroid (1) or carcinoma of unknown
      origin (4)). The metastases were solitary for 22 patients and multiple for 8
      patients. Average ages (y) (+/-SD) were 58.6+/-10.4 for NSC lung patients and
      53.4+/-12.5 (p = 0.32) for non-lung patients. The average interval (months) from
      diagnosis of the primary to metastasis was 23.8+/-41.4 for all patients. This
      interval was shorter for NSC lung patients: 3.1+/-6.0 vs. 48.0+/-51.7 (p < 0.001)
      for non-lung patients. Twenty seven patients had conventional radiotherapy (XRT)
      before (24 patients) or after (3 patients) SRS. Doses (cGy) were 3303+/-841 for
      13 NSC lung patients and 4256+/-992 for 14 non-lung patients (p = 0.034). The
      median time from primary diagnosis to SRS was shorter for the NSC lung patients
      (11 mo) compared to the non-lung patients (35 mo). SRS was given for recurrence
      of metastases after XRT for 11/14 NSC lung patients and 13/16 non-lung patients.
      The doses (cGy) of SRS were 1579+/-484 vs. 1682+/-476 (p=0.45) for the NSC lung
      and non-lung groups, respectively. After SRS a decrease in metastasis diameter
      was observed in 10 of 14 NSC lung patients vs. 12 of 16 non-lung patients (p=0.85
      Chi-square). Twenty-seven of the 30 patients have died. For all patients, the
      median survival after diagnosis of the primary and after radiosurgery was 31.3
      and 8.4 months, respectively. The median survival (95% CI) from primary diagnosis
      was 24.3 months (13.2-27.3) for NSC lung patients and 46.5 months (39.2-65.5) for
      non-lung patients (p=0.005 logrank test). The median survival (95% CI) after SRS
      was 7.9 months (3.0-14.3) for the NSC lung patients and 8.4 (2.9-11.9) months for
      the non-lung patients (p=0.98 logrank test). Within the two groups, no difference
      in survival was observed for patients who had SRS sooner (< 1 yr for NSC lung; <
      3 yr for non-lung) after primary diagnosis: 9.3 vs. 6.5 mo for NSC lung (p=0.21)
      and 10.5 vs. 7.2 mo for non-lung (p=0.87). In this series, the shortened
      intervals from primary diagnosis to SRS for NSC lung metastases was associated
      with post-SRS survivorship that was equivalent to the more favorable non-lung
      group.

PMID- 9525852
TI  - Interaction of short-range repressors with Drosophila CtBP in the embryo.
AB  - Human CtBP attenuates transcriptional activation and tumorigenesis mediated by
      the adenovirus E1A protein. The E1A sequence motif that interacts with CtBP, Pro
      X-Asp-Leu-Ser-X-Lys (P-DLS-K), is present in the repression domains of two
      unrelated short-range repressors in Drosophila, Knirps and Snail, and is
      essential for the interaction of these proteins with Drosophila CtBP (dCtBP). A P
      element-induced mutation in dCtBP exhibits gene-dosage interactions with a null
      mutation in knirps, which is consistent with the occurrence of Knirps-dCtBP
      interactions in vivo. These observations suggest that CtBP and dCtBP are engaged
      in an evolutionarily conserved mechanism of transcriptional repression, which is
      used in both Drosophila and mammals.

PMID- 9525853
TI  - Arabidopsis CBF1 overexpression induces COR genes and enhances freezing
      tolerance.
AB  - Many plants, including Arabidopsis, show increased resistance to freezing after
      they have been exposed to low nonfreezing temperatures. This response, termed
      cold acclimation, is associated with the induction of COR (cold-regulated) genes
      mediated by the C-repeat/drought-responsive element (CRT/DRE) DNA regulatory
      element. Increased expression of Arabidopsis CBF1, a transcriptional activator
      that binds to the CRT/DRE sequence, induced COR gene expression and increased the
      freezing tolerance of nonacclimated Arabidopsis plants. We conclude that CBF1 is
      a likely regulator of the cold acclimation response, controlling the level of COR
      gene expression, which in turn promotes tolerance to freezing.

PMID- 9525854
TI  - Structural conservation in prokaryotic and eukaryotic potassium channels.
AB  - Toxins from scorpion venom interact with potassium channels. Resin-attached,
      mutant K+ channels from Streptomyces lividans were used to screen venom from
      Leiurus quinquestriatus hebraeus, and the toxins that interacted with the channel
      were rapidly identified by mass spectrometry. One of the toxins, agitoxin2, was
      further studied by mutagenesis and radioligand binding. The results show that a
      prokaryotic K+ channel has the same pore structure as eukaryotic K+ channels.
      This structural conservation, through application of techniques presented here,
      offers a new approach for K+ channel pharmacology.

PMID- 9525856
TI  - Integration of environmental, agronomic, and economic aspects of fertilizer
      management 
AB  - Nitrogen fertilization is a substantial source of nitrogen-containing trace gases
      that have both regional and global consequences. In the intensive wheat systems
      of Mexico, typical fertilization practices lead to extremely high fluxes of
      nitrous oxide (N2O) and nitric oxide (NO). In experiments, lower rates of
      nitrogen fertilizer, applied later in the crop cycle, reduced the loss of
      nitrogen without affecting yield and grain quality. Economic analyses projected
      this alternative practice to save 12 to 17 percent of after-tax profits. A
      knowledge-intensive approach to fertilizer management can substitute for higher
      levels of inputs, saving farmers money and reducing environmental costs.

PMID- 9525855
TI  - Requirement of Ras-GTP-Raf complexes for activation of Raf-1 by protein kinase C.
AB  - Receptor tyrosine kinase-mediated activation of the Raf-1 protein kinase is
      coupled to the small guanosine triphosphate (GTP)-binding protein Ras. By
      contrast, protein kinase C (PKC)-mediated activation of Raf-1 is thought to be
      Ras independent. Nevertheless, stimulation of PKC in COS cells led to activation
      of Ras and formation of Ras-Raf-1 complexes containing active Raf-1. Raf-1
      mutations that prevent its association with Ras blocked activation of Raf-1 by
      PKC. However, the activation of Raf-1 by PKC was not blocked by dominant negative
      Ras, indicating that PKC activates Ras by a mechanism distinct from that
      initiated by activation of receptor tyrosine kinases.

PMID- 9525857
TI  - Induction of lens differentiation by activation of a bZIP transcription factor, L
      Maf.
AB  - After the vertebrate lens is induced from head ectoderm, lens-specific genes are
      expressed. Transcriptional regulation of the lens-specific alphaA-crystallin gene
      is controlled by an enhancer element, alphaCE2. A gene encoding an alphaCE2
      binding protein, L-maf(lens-specific maf), was isolated. L-maf expression is
      initiated in the lens placode and is restricted to lens cells. The gene product L
      Maf regulates the expression of multiple genes expressed in the lens, and ectopic
      expression of this transcription factor converts chick embryonic ectodermal cells
      and cultured cells into lens fibers. Thus, vertebrate lens induction and
      differentiation can be triggered by the activation of L-Maf.

PMID- 9525858
TI  - The formation of chondrules: petrologic tests of the shock wave model 
AB  - Chondrules are millimeter-sized rounded igneous rocks within chondritic
      meteorites. Their textures and fractionated mineral chemistries suggest that they
      formed by repeated, localized, brief (minutes to hours) melting of cold
      aggregates of mineral dust in the protoplanetary nebula. Astrophysical models of
      chondrule formation have been unable to explain the petrologically diverse nature
      of chondrites. However, a nebular shock wave model for chondrule formation agrees
      with many of the observed petrologic and geochemical properties of chondrules and
      shows how particles within the nebula are sorted by size and how rims around
      chondrules are formed. It also explains the volatile-rich nature of chondrule
      rims and the chondrite matrix.

PMID- 9525862
TI  - Flower-associated brachycera flies as fossil evidence for jurassic angiosperm
      origins 
AB  - Pollinating insects played a decisive role in the origin and early evolution of
      the angiosperms. Pollinating orthorrhaphous Brachycera fossils (short-horned
      flies) collected from Late Jurassic rocks in Liaoning Province of northeast China
      provide evidence for a pre-Cretaceous origin of angiosperms. Functional
      morphology and comparison with modern confamilial taxa show that the
      orthorrhaphous Brachycera were some of the most ancient pollinators. These data
      thus imply that angiosperms originated during the Late Jurassic and were
      represented by at least two floral types.

PMID- 9525859
TI  - The structure of the potassium channel: molecular basis of K+ conduction and
      selectivity.
AB  - The potassium channel from Streptomyces lividans is an integral membrane protein
      with sequence similarity to all known K+ channels, particularly in the pore
      region. X-ray analysis with data to 3.2 angstroms reveals that four identical
      subunits create an inverted teepee, or cone, cradling the selectivity filter of
      the pore in its outer end. The narrow selectivity filter is only 12 angstroms
      long, whereas the remainder of the pore is wider and lined with hydrophobic amino
      acids. A large water-filled cavity and helix dipoles are positioned so as to
      overcome electrostatic destabilization of an ion in the pore at the center of the
      bilayer. Main chain carbonyl oxygen atoms from the K+ channel signature sequence
      line the selectivity filter, which is held open by structural constraints to
      coordinate K+ ions but not smaller Na+ ions. The selectivity filter contains two
      K+ ions about 7.5 angstroms apart. This configuration promotes ion conduction by
      exploiting electrostatic repulsive forces to overcome attractive forces between
      K+ ions and the selectivity filter. The architecture of the pore establishes the
      physical principles underlying selective K+ conduction.

PMID- 9525860
TI  - Classical conditioning and brain systems: the role of awareness.
AB  - Classical conditioning of the eye-blink response, perhaps the best studied
      example of associative learning in vertebrates, is relatively automatic and
      reflexive, and with the standard procedure (simple delay conditioning), it is
      intact in animals with hippocampal lesions. In delay conditioning, a tone [the
      conditioned stimulus (CS)] is presented just before an air puff to the eye [the
      unconditioned stimulus (US)]. The US is then presented, and the two stimuli
      coterminate. In trace conditioning, a variant of the standard paradigm, a short
      interval (500 to 1000 ms) is interposed between the offset of the CS and the
      onset of the US. Animals with hippocampal lesions fail to acquire trace
      conditioning. Amnesic patients with damage to the hippocampal formation and
      normal volunteers were tested on two versions of delay conditioning and two
      versions of trace conditioning and then assessed for the extent to which they
      became aware of the temporal relationship between the CS and the US. Amnesic
      patients acquired delay conditioning at a normal rate but failed to acquire trace
      conditioning. For normal volunteers, awareness was unrelated to successful delay
      conditioning but was a prerequisite for successful trace conditioning. Trace
      conditioning is hippocampus dependent because, as in other tasks of declarative
      memory, conscious knowledge must be acquired across the training session. Trace
      conditioning may provide a means for studying awareness in nonhuman animals, in
      the context of current ideas about multiple memory systems and the function of
      the hippocampus.

PMID- 9525863
TI  - Capture of interplanetary and interstellar dust by the jovian magnetosphere.
AB  - Interplanetary and interstellar dust grains entering Jupiter's magnetosphere form
      a detectable diffuse faint ring of exogenic material. This ring is composed of
      particles in the size range of 0. 5 to 1.5 micrometers on retrograde and prograde
      orbits in a 4:1 ratio, with semimajor axes 3 < a < 20 jovian radii,
      eccentricities 0. 1 < e < 0.3, and inclinations i less, similar 20 degrees or i
      greater, similar 160 degrees. The size range and the orbital characteristics are
      consistent with in situ detections of micrometer-sized grains by the Galileo dust
      detector, and the measured rates match the number densities predicted from
      numerical trajectory integrations.

PMID- 9525861
TI  - Ultrasound-stimulated vibro-acoustic spectrography.
AB  - An ultrasound method based on radiation force is presented for imaging the
      acoustic response of a material to mechanical excitation. Acoustic energy was
      emitted from solids and tissues in response to an oscillatory radiation force
      produced by interfering focused beams of ultrasound. Frequency spectra of
      ultrasound-stimulated acoustic emission exhibited object resonances. Raster
      scanning the radiation force over the object and recording the amplitude and
      phase of the emitted sound resulted in data from which images related to the
      elastic compositions of the acoustically emitting objects could be computed.
      Acoustic emission signals distinguished tuning-fork resonances, submillimeter
      glass spheres, and calcification in excised arteries and detected object motions
      on the order of nanometers.

PMID- 9525864
TI  - Time scales and heterogeneous structure in geodynamic earth models 
AB  - Computer models of mantle convection constrained by the history of Cenozoic and
      Mesozoic plate motions explain some deep-mantle structural heterogeneity imaged
      by seismic tomography, especially those related to subduction. They also reveal a
      150-million-year time scale for generating thermal heterogeneity in the mantle,
      comparable to the record of plate motion reconstructions, so that the problem of
      unknown initial conditions can be overcome. The pattern of lowermost mantle
      structure at the core-mantle boundary is controlled by subduction history,
      although seismic tomography reveals intense large-scale hot (low-velocity)
      upwelling features not explicitly predicted by the models.

PMID- 9525865
TI  - Strong regularities in world wide web surfing 
AB  - One of the most common modes of accessing information in the World Wide Web is
      surfing from one document to another along hyperlinks. Several large empirical
      studies have revealed common patterns of surfing behavior. A model that assumes
      that users make a sequence of decisions to proceed to another page, continuing as
      long as the value of the current page exceeds some threshold, yields the
      probability distribution for the number of pages that a user visits within a
      given Web site. This model was verified by comparing its predictions with
      detailed measurements of surfing patterns. The model also explains the observed
      Zipf-like distributions in page hits observed at Web sites.

PMID- 9525866
TI  - Searching the world wide Web 
AB  - The coverage and recency of the major World Wide Web search engines was analyzed,
      yielding some surprising results. The coverage of any one engine is significantly
      limited: No single engine indexes more than about one-third of the "indexable
      Web," the coverage of the six engines investigated varies by an order of
      magnitude, and combining the results of the six engines yields about 3.5 times as
      many documents on average as compared with the results from only one engine.
      Analysis of the overlap between pairs of engines gives an estimated lower bound
      on the size of the indexable Web of 320 million pages.

PMID- 9525869
TI  - A 37-amino acid sequence in the skeletal muscle ryanodine receptor interacts with
      the cytoplasmic loop between domains II and III in the skeletal muscle
      dihydropyridine receptor.
AB  - Interactions between the Ca2+ release channel of skeletal muscle sarcoplasmic
      reticulum (ryanodine receptor or RyR1) and the loop linking domains II and III
      (II-III loop) of the skeletal muscle L-type Ca2+ channel (dihydropyridine
      receptor or DHPR) are critical for excitation-contraction coupling in skeletal
      muscle. The DHPR II-III loop was fused to glutathione S-transferase- or His
      peptide and used as a protein affinity column for 35S-labeled in vitro translated
      fragments from the N-terminal three-fourths of RyR1. RyR1 residues Leu922-Asp1112
      bound specifically to the DHPR II-III loop column, but the corresponding fragment
      from the cardiac ryanodine receptor (RyR2) did not. The use of chimeras between
      RyR1 and RyR2 localized the interaction to 37 amino acids, Arg1076-Asp1112, in
      RyR1. The RyR1 922-1112 fragment did not bind to the cardiac DHPR II-III loop but
      did bind to the skeletal muscle Na+ channel II-III loop. The skeletal DHPR II-III
      loop double mutant K677E/K682E lost most of its capacity to interact with RyR1,
      suggesting that two positively charged residues are important in the interaction
      between RyR and DHPR.

PMID- 9525868
TI  - A single BIR domain of XIAP sufficient for inhibiting caspases.
AB  - The inhibitor of apoptosis proteins (IAPs) constitute an evolutionarily conserved
      family of homologous proteins that suppress apoptosis induced by multiple
      stimuli. Some IAP family proteins, including XIAP, cIAP-1, and cIAP-2, can bind
      and directly inhibit selected caspases, a group of intracellular cell death
      proteases. These caspase-inhibiting IAP family proteins all contain three tandem
      BIR domains followed by a RING zinc finger domain. To determine the structural
      basis for caspase inhibition by XIAP, we analyzed the effects of various
      fragments of this IAP family protein on caspase activity in vitro and on
      apoptosis suppression in intact cells. The RING domain of XIAP failed to inhibit
      the activity of recombinant caspases-3 or -7, whereas a fragment of XIAP
      encompassing the three tandem BIR domains potently inhibited these caspases in
      vitro and blocked Fas (CD95)-induced apoptosis when expressed in cells. Further
      dissection of the XIAP protein demonstrated that only the second of the three BIR
      domains (BIR2) was capable of binding and inhibiting these caspases. The apparent
      inhibition constants (Ki) for BIR2-mediated inhibition of caspases-3 and -7 were
      2-5 nM, indicating that this single BIR domain possesses potent anti-caspase
      activity. Expression of the BIR2 domain in cells also partially suppressed Fas
      induced apoptosis and blocked cytochrome c-induced processing of caspase-9 in
      cytosolic extracts, whereas BIR1 and BIR3 did not. These findings identify BIR2
      as the minimal caspase-inhibitory domain of XIAP and indicate that a single BIR
      domain can be sufficient for binding and inhibiting caspases.

PMID- 9525867
TI  - Blk, a BH3-containing mouse protein that interacts with Bcl-2 and Bcl-xL, is a
      potent death agonist.
AB  - We identified and cloned a novel murine member of the pro-apoptotic Bcl-2 family.
      This protein, designated Blk, is structurally and functionally related to human
      Bik and localized to the mitochondrial membrane. Blk contains a conserved BH3
      domain and can interact with the anti-apoptotic proteins Bcl-2 and Bcl-xL.
      Ectopic expression of Blk in mammalian cells induces apoptosis, which can be
      inhibited by mutations in the BH3 domain and by overexpression of Bcl-2 or Bcl-xL
      but not by CrmA. The apoptotic activity of Blk is also inhibited by a dominant
      negative caspase-9, suggesting that Blk induces apoptosis through activation of
      the cytochrome c-Apaf-1-caspase-9 pathway.

PMID- 9525870
TI  - The cancer-predisposing mutation C61G disrupts homodimer formation in the NH2
      terminal BRCA1 RING finger domain.
AB  - The breast and ovarian cancer tumor suppressor gene, BRCA1, encodes for a Zn2+
      binding RING finger motif located near the protein NH2 terminus. The RING finger
      motif is characterized by eight conserved Cys and His residues which form two
      Zn2+-binding sites termed Site I and Site II. We used limited proteolysis in
      conjunction with matrix-assisted laser desorption ionization time-of-flight mass
      spectroscopy to investigate the metal binding properties and to probe the
      solution structures of wild-type and mutant BRCA1 constructs that include the
      RING finger. Our results show that the RING finger motif is part of a larger
      proteolysis-resistant structural domain which encompasses the first 110 residues
      of BRCA1. Analytical gel-filtration chromatography and chemical cross-linking
      experiments demonstrate that the BRCA1 NH2-terminal domain readily homodimerizes
      in solution. The cancer-predisposing C61G mutation, which alters a conserved Zn2+
      binding residue, abolishes metal binding to Site II of the RING finger motif,
      while Site I remains intact and functional. The C61G mutation also results in
      increased proteolytic susceptibility of the COOH-terminal portion of the NH2
      terminal domain and perturbs the oligomerization properties of BRCA1.

PMID- 9525871
TI  - Human chorionic gonadotropin-alpha gene is transcriptionally activated by
      epidermal growth factor through cAMP response element in trophoblast cells.
AB  - The purpose of this study was to analyze the mechanism of transcriptional
      activation of human chorionic gonadotropin-alpha (hCGalpha) gene by epidermal
      growth factor (EGF) in trophoblast cells. We stably transfected hCGalpha promoter
      chloramphenicol acetyltransferase constructs into Rcho-1 trophoblast cells and
      monitored the promoter activities. -290-base pair hCGalpha promoter containing a
      tandem repeat of cAMP response element (CRE) was activated by EGF in a dose- and
      time-dependent manner. Deletion analysis of hCGalpha promoter suggested an
      involvement of CRE in EGF-induced hCGalpha transcriptional activation. Moreover,
      the hCGalpha promoter, of which both CREs were mutated, did not respond to EGF.
      These results indicate that EGF activates the hCGalpha gene transcription through
      CRE. Although EGF did not alter the amount of CRE-binding protein (CREB), EGF
      induced CREB phosphorylation. We next examined the mechanism of CREB
      phosphorylation by EGF. Protein kinase C inhibitors (H7, staurosporin, and
      chelerythrine) inhibited EGF-induced CREB phosphorylation, whereas either mitogen
      activated protein kinase kinase-1 inhibitor (PD98059) or protein kinase A
      inhibitor (H8) showed no effect. Furthermore, H7 and staurosporin but not H8
      inhibited hCGalpha promoter activation by EGF. In conclusion, EGF promotes
      hCGalpha gene transcription via the CRE region probably by phosphorylating CREB
      mainly through the protein kinase C pathway in trophoblast cells.

PMID- 9525872
TI  - A Gly --> Ser change causes defective folding in vitro of calcium-binding
      epidermal growth factor-like domains from factor IX and fibrillin-1.
AB  - The calcium-binding epidermal growth factor-like (cbEGF) domain is a common motif
      found in extracellular proteins. A mutation that changes a highly conserved Gly
      residue to Ser in this domain has been identified both in the factor IX (FIX) and
      fibrillin-1 genes, where it is associated with relatively mild variants of
      hemophilia B and Marfan syndrome, respectively. We have investigated the
      structural consequences in vitro of this amino acid change when introduced into
      single cbEGF domains from human FIX (G60S) and human fibrillin-1 (G1127S), and a
      covalently linked pair of cbEGF domains from fibrillin-1. High pressure liquid
      chromatography analysis, mass spectrometry, and 1H NMR analysis demonstrate that
      wild-type cbEGF domains purified in the reduced form and refolded in vitro adopt
      the native fold. In contrast, the Gly --> Ser change causes defective folding of
      FIX and fibrillin-1 cbEGF domains. However, in the case of the factor IX mutant
      domain, a Ca2+-dependent change in conformation, identified by NMR in a
      proportion of the refolded material, suggests that some material refolds to a
      native-like structure. This is consistent with enzyme-linked immunosorbent assay
      analysis of FIX G60S from a hemophilia B patient Oxford d2, which demonstrates
      that the mutant protein is partially recognized by a monoclonal antibody specific
      for this region of FIX. NMR analysis of a covalently linked pair of fibrillin
      cbEGF domains demonstrates that the C-terminal domain adopts the native epidermal
      growth factor fold, despite the fact that the adjacent mutant domain is
      misfolded. The implications of these results for disease pathogenesis are
      discussed.

PMID- 9525873
TI  - Enzymatic hydrolysis of organic cyclic carbonates.
AB  - Ethylene carbonate, a cyclic organic carbonate widely used industrially, is toxic
      when metabolically converted to ethylene glycol. A rat liver enzyme active in
      catalyzing the ring opening has been purified to electrophoretic homogeneity and
      found to be active in the hydrolysis of ethylene, vinylene, and propylene
      carbonates to CO2 and the respective glycols. Neither thiocarbonates nor open
      chain carbonates served as substrate nor did a variety of esters, lactams,
      lactones, and related heterocycles. The enzyme was active, however, with imides
      and appears to be identical to rat liver imidase. The identification was
      confirmed by copurification of enzyme activities, by similarities in the pattern
      of inhibition, and by the reactivity with a polyclonal antibody directed against
      the enzyme purified here.

PMID- 9525875
TI  - Xanthine oxidase-mediated decomposition of S-nitrosothiols.
AB  - S-Nitrosothiols (RSNO) occur in vivo and have been proposed as nitric oxide (.NO)
      storage and transport biomolecules. Still, the biochemical mechanisms by which
      RSNO release .NO in biological systems are not well defined, and in particular,
      the interactions between reactive oxygen species and RSNO have not been studied.
      In this work, we show that xanthine oxidase (XO), in the presence of purine
      (hypoxanthine, xanthine) or pteridine (lumazine) substrates, induces S
      nitrosocysteine (CysNO) and S-nitrosoglutathione (GSNO) decomposition under
      aerobic conditions. The decomposition of RSNO by XO was inhibitable by copper
      zinc superoxide dismutase, in agreement with the participation of superoxide
      anion (O-2) in the process. However, while superoxide dismutase could totally
      inhibit aerobic decomposition of GSNO, it was only partially inhibitory for
      CysNO. Competition experiments indicated that O-2 reacted with GSNO with a rate
      constant of 1 x 10(4) M-1.s-1 at pH 7.4 and 25 degreesC. The decomposition of
      RSNO was accompanied by peroxynitrite formation as assessed by the oxidation of
      dihydrorhodamine and of cytochrome c2+. The proposed mechanism involves the O-2
      dependent reduction of RSNO to yield .NO, which in turn reacts fast with a second
      O-2 molecule to yield peroxynitrite. Under anaerobic conditions, CysNO incubated
      with xanthine plus XO resulted in CysNO decomposition, .NO detection, and
      cysteine and uric acid formation. We found that CysNO is an electron acceptor
      substrate for XO with a Km of 0.7 mM. In agreement with this concept, the
      enzymatic reduction of CysNO by XO was inhibitable by oxypurinol and
      diphenyliodonium, inhibitors that interfere with the catalytic cycle at the
      molybdenum and flavin sites, respectively. In conclusion, XO decomposes RSNO by O
      2-dependent and -independent pathways, and in the presence of oxygen it leads to
      peroxynitrite formation.

PMID- 9525874
TI  - Introduction of a tryptophan reporter group into the ATP binding motif of the
      Escherichia coli UvrB protein for the study of nucleotide binding and
      conformational dynamics.
AB  - The DNA-dependent ATPase activity of UvrB is required to support preincision
      steps in nucleotide excision repair in Escherichia coli. This activity is,
      however, cryptic. Elicited in nucleotide excision repair by association with the
      UvrA protein, it may also be unmasked by a specific proteolysis eliminating the C
      terminal domain of UvrB (generating UvrB*). We introduced fluorescent reporter
      groups (tryptophan replacing Phe47 or Asn51) into the ATP binding motif of UvrB,
      without significant alteration of behavior, to study both nucleotide binding and
      those conformational changes expected to be essential to function. The inserted
      tryptophans occupy moderately hydrophobic, although potentially heterogeneous,
      environments as evidenced by fluorescence emission and time-resolved decay
      characteristics, yet are accessible to the diffusible quencher acrylamide.
      Activation, via specific proteolysis, is accompanied by conformational change at
      the ATP binding site, with multiple changes in emission spectra and a greater
      shielding of the tryptophans from diffusible quencher. Titration of tryptophan
      fluorescence with ATP has revealed that, although catalytically incompetent, UvrB
      can bind ATP and bind with an affinity equal to that of the active UvrB* form (Kd
      of approximately 1 mM). The ATP binding site of UvrB is therefore functional and
      accessible, suggesting that conformational change either brings amino acid
      residues into proper alignment for catalysis and/or enables response to effector
      DNA.

PMID- 9525876
TI  - DNA structural elements required for ERCC1-XPF endonuclease activity.
AB  - The heterodimeric complex ERCC1-XPF is a structure-specific endonuclease
      responsible for the 5' incision during mammalian nucleotide excision repair
      (NER). Additionally, ERCC1-XPF is thought to function in the repair of
      interstrand DNA cross-links and, by analogy to the homologous Rad1-Rad10 complex
      in Saccharomyces cerevisiae, in recombination between direct repeated DNA
      sequences. To gain insight into the role of ERCC1-XPF in such recombinational
      processes and in the NER reaction, we studied in detail the DNA structural
      elements required for ERCC1-XPF endonucleolytic activity. Recombinant ERCC1-XPF,
      purified from insect cells, was found to cleave stem-loop substrates at the DNA
      junction in the absence of other proteins like replication protein A, showing
      that the structure-specific endonuclease activity is intrinsic to the complex.
      Cleavage depended on the presence of divalent cations and was optimal in low Mn2+
      concentrations (0.2 mM). A minimum of 4-8 unpaired nucleotides was required for
      incisions by ERCC1-XPF. Splayed arm and flap substrates were also cut by ERCC1
      XPF, resulting in the removal of 3' protruding single-stranded arms. All
      incisions occurred in one strand of duplex DNA at the 5' side of a junction with
      single-stranded DNA. The exact cleavage position varied from 2 to 8 nucleotides
      away from the junction. One single-stranded arm, protruding either in the 3' or
      5' direction, was necessary and sufficient for correct positioning of incisions
      by ERCC1-XPF. Our data specify the engagement of ERCC1-XPF in NER and allow a
      more direct search for its specific role in recombination.

PMID- 9525877
TI  - Epibatidine binds with unique site and state selectivity to muscle nicotinic
      acetylcholine receptors.
AB  - Ligand binding sites in fetal (alpha2betagammadelta) and adult
      (alpha2betadeltaepsilon) muscle acetylcholine receptors are formed by alphadelta,
      alphagamma, or alphaepsilon subunit pairs. Each type of binding site shows unique
      ligand selectivity due to different contributions by the delta, gamma, or epsilon
      subunits. The present study compares epibatidine and carbamylcholine binding in
      terms of their site and state selectivities for muscle receptors expressed in
      human embryonic kidney 293 cells. Measurements of binding to alphagamma,
      alphadelta, and alphaepsilon intracellular complexes reveal opposite site
      selectivities between epibatidine and carbamylcholine; for epibatidine the rank
      order of affinities is alphaepsilon > alphagamma > alphadelta, whereas for
      carbamylcholine the rank order is alphadelta congruent with alphaepsilon >
      alphagamma. Because the relative affinities of intracellular complexes resemble
      those of receptors in the closed activable state, the results suggest that
      epibatidine binds with unique site selectivity in activating the muscle receptor.
      Measurements of binding at equilibrium show that both enantiomers of epibatidine
      bind to adult and fetal receptors with shallow but monophasic binding curves.
      However, when receptors are fully desensitized, epibatidine binds in a biphasic
      manner, with dissociation constants of the two components differing by more than
      170-fold. Studies of subunit-omitted receptors (alpha2betadelta2,
      alpha2betagamma2, and alpha2betaepsilon2) reveal that in the desensitized state,
      the alphadelta interface forms the low affinity epibatidine site, whereas the
      alphagamma and alphaepsilon interfaces form high affinity sites. In contrast to
      epibatidine, carbamylcholine shows little site selectivity for desensitized fetal
      or adult receptors. Thus epibatidine is a potentially valuable probe of
      acetylcholine receptor binding site structure and of elements that confer state
      dependent selectivities of the binding sites.

PMID- 9525878
TI  - Modulation of oxidative phosphorylation by Mg2+ in rat heart mitochondria.
AB  - The effect of varying the Mg2+ concentration on the 2-oxoglutarate dehydrogenase
      (2-OGDH) activity and the rate of oxidative phosphorylation of rat heart
      mitochondria was studied. The ionophore A23187 was used to modify the
      mitochondrial free Mg2+ concentration. Half-maximal stimulation (K0.5) of ATP
      synthesis by Mg2+ was obtained with 0.13 +/- 0.02 mM (n = 7) with succinate
      (+rotenone) and 0.48 +/- 0.13 mM (n = 6) with 2-oxoglutarate (2-OG) as
      substrates. Similar K0.5 values were found for NAD(P)H formation, generation of
      membrane potential, and state 4 respiration with 2-OG. In the presence of ADP, an
      increase in Pi concentration promoted a decrease in the K0.5 values of ATP
      synthesis, membrane potential formation and state 4 respiration for Mg2+ with 2
      OG, but not with succinate. These results indicate that 2-OGDH is the main step
      of oxidative phosphorylation modulated by Mg2+ when 2-OG is the oxidizable
      substrate; with succinate, the ATP synthase is the Mg2+-sensitive step.
      Replacement of Pi by acetate, which promotes changes on intramitochondrial pH
      abolished Mg2+ activation of 2-OGDH. Thus, the modulation of the 2-OGDH activity
      by Mg2+ has an essential requirement for Pi (and ADP) in intact mitochondria
      which is not associated to variations in matrix pH.

PMID- 9525879
TI  - Connexin membrane protein biosynthesis is influenced by polypeptide positioning
      within the translocon and signal peptidase access.
AB  - We reported previously (Falk, M. M., Kumar, N. M., and Gilula, N. B. (1994) J.
      Cell Biol. 127, 343-355) that the membrane integration of polytopic connexin
      polypeptides can be accompanied by an inappropriate cleavage that generates amino
      terminal truncated connexins. While this cleavage was not detected in vivo,
      translation in standard cell-free translation/translocation systems resulted in
      the complete cleavage of all newly integrated connexins. Partial cleavage
      occurred in heterologous expression systems that correlated with the expression
      level. Here we report that the transmembrane topology of connexins generated in
      microsomal membranes was identical to the topology of functional connexins in
      plasma membranes. Characterization of the cleavage site and reaction showed that
      the connexins were processed by signal peptidase immediately downstream of their
      first transmembrane domain in a reaction similar to the removal of signal
      peptides from pre-proteins. Increasing the length and hydrophobic character of
      the signal anchor sequence of connexins completely prevented the aberrant
      cleavage. This result indicates that their signal anchor sequence was falsely
      recognized and positioned as a cleavable signal peptide within the endoplasmic
      reticulum translocon, and that this mispositioning enabled signal peptidase to
      access the cleavage sites. The results provide direct evidence for the
      involvement of unknown cellular factors in the membrane integration process of
      connexins.

PMID- 9525880
TI  - Molecular cloning, sequencing, and heterologous expression of the vaoA gene from
      Penicillium simplicissimum CBS 170.90 encoding vanillyl-alcohol oxidase.
AB  - The cDNA encoding vanillyl-alcohol oxidase (EC 1.1.3.7) was selected from a cDNA
      library constructed from mRNA isolated from Penicillium simplicissimum CBS 170.90
      grown on veratryl alcohol by immunochemical screening. The vaoA-cDNA nucleotide
      sequence revealed an open reading frame of 1680 base pairs encoding a 560-amino
      acid protein with a deduced mass of 62,915 Da excluding the covalently bound FAD.
      The deduced primary structure shares 31% sequence identity with the 8alpha-(O
      tyrosyl)-FAD containing subunit of the bacterial flavocytochrome p-cresol methyl
      hydroxylase. The vaoA gene was isolated from a P. simplicissimum genomic library
      constructed in lambdaEMBL3 using the vaoA-cDNA as a probe. Comparison of the
      nucleotide sequence of the vaoA gene with the cDNA nucleotide sequence
      demonstrated that the gene is interrupted by five short introns. Aspergillus
      niger NW156 prtF pyrA leuA cspA transformed with the pyrA containing plasmid and
      a plasmid harboring the complete vaoA gene including the promoter and terminator
      was able to produce vaoA mRNA and active vanillyl-alcohol oxidase when grown on
      veratryl alcohol and anisyl alcohol. A similar induction of the vaoA gene was
      found for P. simplicissimum, indicating that similar regulatory systems are
      involved in the induction of the vaoA gene in these fungi. Introduction of a
      consensus ribosome binding site, AGAAGGAG, in the vaoA-cDNA resulted in elevated
      expression levels of active vanillyl-alcohol oxidase from the lac promoter in
      Escherichia coli TG2. The catalytic and spectral properties of the purified
      recombinant enzyme were indistinguishable from the native enzyme.

PMID- 9525883
TI  - The action of DNA ligase at abasic sites in DNA.
AB  - Apurinic/apyrimidinic (AP) sites occur frequently in DNA as a result of
      spontaneous base loss or following removal of a damaged base by a DNA
      glycosylase. The action of many AP endonuclease enzymes at abasic sites in DNA
      leaves a 5'-deoxyribose phosphate (dRP) residue that must be removed during the
      base excision repair process. This 5'-dRP group may be removed by AP lyase
      enzymes that employ a beta-elimination mechanism. This beta-elimination reaction
      typically involves a transient Schiff base intermediate that can react with
      sodium borohydride to trap the DNA-enzyme complex. With the use of this assay as
      well as direct 5'-dRP group release assays, we show that T4 DNA ligase, a
      representative ATP-dependent DNA ligase, contains AP lyase activity. The AP lyase
      activity of T4 DNA ligase is inhibited in the presence of ATP, suggesting that
      the adenylated lysine residue is part of the active site for both the ligase and
      lyase activities. A model is proposed whereby the AP lyase activity of DNA ligase
      may contribute to the repair of abasic sites in DNA.

PMID- 9525881
TI  - A reduced folate carrier mutation produces substrate-dependent alterations in
      carrier mobility in murine leukemia cells and methotrexate resistance with
      conservation of growth in 5-formyltetrahydrofolate.
AB  - With 5-formyltetrahydrofolate (5-CHO-THF) as the folate source a methotrexate
      (MTX) transport-deficient murine leukemia cell line, L1210-G1a, was isolated
      after chemical mutagenesis and MTX selection. This cell line was 10-fold
      resistant to MTX in comparison to parental L1210 cells, yet the EC50 for 5-CHO
      THF was increased by a factor of only 2. The initial uptake of MTX, at a
      concentration of 1 microM, was decreased by a factor of 40, whereas influx of 5
      CHO-THF dropped by a factor of only 8. This difference in initial uptake rates
      was attributed solely to changes in influx Vmax without a significant change in
      Km. Whereas the RFC1 mRNA level in L1210-G1a cells was indistinguishable from
      that of parental L1210 cells, a serine to asparagine substitution was identified
      at amino acid 46 within the first predicted transmembrane domain. This was a
      result of a homozygous mutation of G-->A in the genome. Transfection of the
      mutated RFC1 cDNA into MTXrA cells, which lack functional endogenous carrier,
      resulted in a clonal derivative MTXrA-S46N. The increase in influx of 5-CHO-THF
      and 5-CH3THF was 5 and 13 times greater than that for MTX in the transfectant,
      consistent with the influx ratio in the L1210-G1a line. The functional expression
      of the mutated RFC1 reduced the growth requirement for 5-CHO-THF by a factor of
      30, compared with only a 3-fold decrease in the MTX IC50. This represents the
      first reported RFC1 mutation that confers resistance to MTX due to a markedly
      impaired influx with relative conservation of reduced folate transport. The
      kinetic changes are consistent with a substrate-dependent alteration in carrier
      mobility that favors reduced folates over MTX. These changes may account for the
      development of MTX resistance due to impaired drug transport in vivo, allowing
      tumor cells to meet their folate requirement with 5-CH3THF, the predominant blood
      folate.

PMID- 9525882
TI  - Increased DNA unwinding efficiency of bacteriophage T7 DNA helicase mutant
      protein 4A'/E348K.
AB  - Bacteriophage T7 4A' protein is a DNA helicase that unwinds DNA in a reaction
      coupled to dTTP hydrolysis. To understand better its mechanism of DNA unwinding,
      we characterized a set of 4A' mutant proteins (Washington, M. T., Rosenberg, A.
      H., Griffin, K., Studier, F. W., and Patel, S. S. (1996) J. Biol. Chem. 271,
      26825-26834). We showed here, using single turnover DNA unwinding assays, that
      the 4A'/E348K mutant protein had the unusual property of unwinding DNA (with a 5
      6-fold slower rate) despite a significant defect in its dTTPase activity (a 25-30
      fold slower rate). Comparing the DNA unwinding rates to the dTTPase rates, we
      estimated the DNA unwinding efficiencies of both wild-type (about 1 base pair
      unwound per dTTP hydrolysis) and mutant (4 to 6 base pairs unwound per dTTP
      hydrolysis). Thus the mutant had a 4-6-fold improvement in its DNA unwinding
      efficiency over that of the wild-type. We believe that this mutant undergoes less
      slippage (uncoupled dTTP hydrolysis) than the wild-type. We speculate that nature
      has selected for a high rate of DNA unwinding rather than a high efficiency of
      DNA unwinding. Thus even though the mutant is more efficient at DNA unwinding,
      the wild-type probably was selected because it unwinds DNA faster.

PMID- 9525884
TI  - The alpha-subunit of the colonic H+,K+-ATPase assembles with beta1-Na+,K+-ATPase
      in kidney and distal colon.
AB  - Previous experiments from our laboratory (Codina, J., Kone, B. C., Delmas-Mata,
      J. T., and DuBose, T. D., Jr. (1996) J. Biol. Chem. 271, 29759-29763)
      demonstrated that the alpha-subunit of the colonic H+, K+-ATPase (HKalpha2)
      requires coexpression with a beta-subunit to support H+/K+ transport in a
      heterologous expression system (Xenopus laevis oocytes). In these studies,
      HKalpha2 formed stable and functional alpha.beta complexes when coexpressed with
      either the rat beta1-subunit of the Na+,K+-ATPase or the beta-subunit of the
      gastric H+,K+-ATPase, suggesting that different beta-subunits may interact with
      HKalpha2. The present studies tested this hypothesis by development and
      application of a specific antibody against HKalpha2 peptide. Subsequently,
      immunoprecipitation experiments were performed to determine if HKalpha2 co
      precipitates with the same beta-subunit in organs known to express HKalpha2
      protein. The data demonstrate that HKalpha2 assembles with beta1-Na+,K+-ATPase in
      the renal medulla and in distal colon.

PMID- 9525885
TI  - Deletions in the third intracellular loop of the thyrotropin receptor. A new
      mechanism for constitutive activation.
AB  - Gain-of-function mutations of the thyrotropin receptor (TSHR) gene have been
      invoked as one of the major causes of toxic thyroid adenomas. In a toxic thyroid
      nodule, we recently identified a 9-amino acid deletion (amino acid positions 613
      621) within the third intracellular (i3) loop of the TSHR resulting in
      constitutive receptor activity. This finding exemplifies a new mechanism of TSHR
      activation and raises new questions concerning the function of the i3 loop.
      Because the i3 loop is thought to be critical for receptor/G protein interaction
      in many receptors, we systematically reexamined the role of the TSHR's i3 loop
      for G protein coupling. Thus, various deletion mutants were generated and
      functionally characterized. We identified an optimal deletion length responsible
      for constitutive activity. If the number of deleted amino acids was reduced,
      elevated basal cAMP accumulation was found to be concomitantly diminished.
      Expansion of the deletion dramatically impaired cell surface expression of the
      receptor. Shifting the deletion toward the N terminus of the i3 loop resulted in
      unaltered strong constitutive receptor activity. In contrast, translocation of
      the deletion toward the C terminus led to significantly reduced basal cAMP
      formation, most probably due to destruction of a conserved cluster of amino
      acids. In this study, we show for the first time that amino acid deletions within
      the i3 loop of a G protein-coupled receptor result in constitutive receptor
      activity. In the TSHR, 75% of the i3 loop generally assumed to play an essential
      role in G protein coupling can be deleted without rendering the mutant receptor
      unresponsive to thyrotropin. These findings support a novel model explaining the
      molecular events accompanying receptor activation by agonist.

PMID- 9525887
TI  - Noncompetitive, chemokine-mediated inhibition of basic fibroblast growth factor
      induced endothelial cell proliferation.
AB  - The proinflammatory and chemoattractant chemokine interleukin-8 (IL-8) inhibits
      cell proliferation induced by basic fibroblast growth factor (bFGF) in mouse
      endothelial cells isolated from subcutaneous sponge implant (sponge-induced mouse
      endothelial cells) and in bovine aortic endothelial GM 7373 cells. The mechanism
      of action of IL-8 was investigated in GM 7373 cells. IL-8 did not prevent the
      binding of bFGF to its tyrosine kinase FGF receptors (FGFRs) nor to cell surface
      heparan sulfate proteoglycans (HSPGs). A transient interaction of IL-8 with the
      cell before the addition of the growth factor was sufficient to prevent bFGF
      activity. The inhibitory activity of IL-8 was abolished by protein kinase C (PKC)
      inhibitors and was mimicked by the PKC activator 12-O-tetradecanoylphorbol-13
      acetate. Accordingly, both IL-8 and 12-O-tetradecanoylphorbol-13-acetate caused a
      approximately 60% decrease of the binding capacity of GM 7373 cells due to the
      down-regulation of FGFRs. Several C-X-C and C-C chemokines exerted an inhibitory
      action on bFGF activity similar to IL-8. Soluble heparin, 6-O-desulfated heparin,
      N-desulfated heparin, and heparan sulfate but not 2-O-desulfated heparin,
      chondroitin-4-sulfate, hyaluronic acid, and K5 polysaccharide abrogated IL-8
      inhibitory activity consistently with the presence of low affinity, high capacity
      HSPG-like chemokine-binding sites on GM 7373 cells. Finally, neovascularization
      induced by bFGF in murine subcutaneous sponge implants was reduced significantly
      by IL-8. In conclusion, IL-8 inhibits the mitogenic activity exerted by bFGF on
      cultured endothelial cells by a PKC-dependent, noncompetitive mechanism of action
      that causes FGFR down-regulation. This activity is shared by several chemokines
      and requires endothelial cell surface HSPGs. The endothelial cell line utilized
      in the present study may help to elucidate the complex interplay among
      chemokines, HSPGs, growth factors, and receptors in endothelial cells.

PMID- 9525886
TI  - Characterization of a novel subtype of human G protein-coupled receptor for
      lysophosphatidic acid.
AB  - The recent identification of the Vzg-1/Edg2 protein as a functional G protein
      coupled receptor for lysophosphatidic acid (LPA) has allowed a sequence-based
      search for new genes that may encode novel subtypes of LPA receptors. A human
      cDNA encoding a G protein-coupled receptor, designated Edg4, was identified by
      searching the GenBankTM for homologs of the human Edg2 LPA receptor. The Edg4
      protein is 46% identical and 72% similar in amino acid sequence to human Edg2.
      When overexpressed in Jurkat T cells, the Edg4 protein mediated LPA-induced
      activation of a serum response element reporter gene with LPA concentration
      dependence (EC50 of 10 nM) and specificity. This LPA-induced reporter gene
      activation could be partially inhibited by pretreatment with pertussis toxin or
      C3 exoenzyme, suggesting requirements for both a Gi protein and Rho GTPase.
      Overexpression of Edg4 in Jurkat cells also led to increases in specific binding
      sites for [3H]LPA. Northern blots revealed that two edg4 mRNA transcripts of 1.8
      and 8 kilobases are distributed very differently from edg2 mRNAs in adult human
      tissues and several cancer cell lines. The existence and distinctive tissue
      expression of structurally different subtypes of LPA receptors may provide one
      basis for tissue-specific functions and permit independent regulation of each
      subtype of LPA receptor.

PMID- 9525888
TI  - Identification of the binding partners for flightless I, A novel protein bridging
      the leucine-rich repeat and the gelsolin superfamilies.
AB  - Flightless-I (fliI) is a novel member of the gelsolin family that is important
      for actin organization during Drosophila embryogenesis and myogenesis. Drosophila
      fliI and the human homolog FLI both contain the classic gelsolin 6-fold segmental
      repeats and an amino-terminal extension of 16 tandem leucine-rich repeats (LRR).
      LRR repeats form amphipathic beta-alpha structural units that mediate protein
      protein interactions. Although there are close to 100 known LRR domain-containing
      proteins, only a few binding pairs have been identified. In this paper, we used
      biochemical and genetic approaches to identify proteins that interact with human
      FLI. In vitro synthesized FLI bound to actin-Sepharose and binding was reduced by
      competition with excess soluble actin. Actin binding was mediated through the
      gelsolin-like domain and not the LRR domain. Although the FLI LRR module is most
      closely related to the LRR domains of Ras-interactive proteins, FLI does not
      associate with Ras, selected Ras effectors, or other Ras-related small GTPases.
      Two-hybrid screens using FLI LRR as bait identified a novel LRR binding partner.
      The 0.65-kilobase pair (kb) clone from the screen survived additional rounds of
      stringent two-hybrid pairwise assays, establishing a specific interaction.
      Binding to FLI LRR was corroborated by co-immunoprecipitation with FLI LRR. The
      translated sequence of the FLI LRR associated protein (FLAP) encodes a novel
      protein not represented in the data base. Northern blot analyses revealed four
      FLAP messages of approximately 2.7, 2.9, 3.3, and 5.1 kb, which are
      differentially expressed in the tissues tested. Skeletal and cardiac muscles are
      particularly rich in the 3.3-kb FLAP message, and the FLI message as well. Full
      length FLAP clones were isolated from a mouse skeletal muscle cDNA library. They
      have an open reading frame which encodes for a protein containing 626 amino
      acids. Sequence analyses predict that the FLAP protein is rich in alpha-helices
      and contains stretches of dimeric coiled coil in its middle region and COOH
      terminus. The identification of actin and FLAP as the binding ligands for the
      gelsolin-like domain and the LRR domain, respectively, suggests that FLI may link
      the actin cytoskeleton to other modules implicated in intermolecular recognition
      and structural organization.

PMID- 9525889
TI  - Receptor-mediated transfection of murine and ovine mammary glands in vivo.
AB  - Transfection of HC-11 murine epithelial mammary cells as well as murine and sheep
      mammary glands were carried out using insulin-containing constructs that deliver
      DNA by receptor-mediated endocytosis to receptor-expressing cells. In vivo
      transfection of mammary gland tissue with the luciferase gene was carried out by
      introducing the DNA constructs into the mammary ducts of both mice and sheep. The
      successful transfection of ewe mammary glands was demonstrated by the detection
      of luciferase activity in mammary gland biopsy material up to a month after a
      single administration of the construct. To test whether products of expression of
      transfected genes could be secreted into the milk in this system, the N-terminal
      secretory signal sequences of bovine beta-lactoglobulin or the entire coding
      sequence of human alpha-lactalbumin were fused to the N terminus of the
      luciferase gene. After transfection with the modified luciferases, both murine
      and sheep milk could be shown to contain luciferase activity, whereas mice, which
      had been transfected with the nonmodified luciferase gene, did not secrete any
      activity in the milk. This approach demonstrates for the first time the
      possibility of gene transfer in vivo into mammary gland epithelial cells using
      constructs delivering DNA via receptor-mediated endocytosis.

PMID- 9525890
TI  - Determinants of gi1alpha and beta gamma binding. Measuring high affinity
      interactions in a lipid environment using flow cytometry.
AB  - G protein heterocomplex undergoes dissociation and association during its
      functional cycle. Quantitative measurements of alpha and betagamma subunit
      binding have been difficult due to a very high affinity. We used fluorescence
      flow cytometry to quantitate binding of fluorescein-labeled Gi1alpha (F-alpha) to
      picomolar concentrations of biotinylated G beta gamma. Association in Lubrol
      solution was rapid (kon = 0.7 x 10(6) M-1 s-1), and equilibrium binding revealed
      a Kd of 2.9 +/- 0.8 nM. The binding showed a complex dependence on magnesium
      concentration, but activation of F-alpha with either GDP/aluminum fluoride or
      guanosine 5'-O-(3-thiotriphosphate) completely prevented formation of the
      heterocomplex (Kd > 100 nM). The binding was also influenced by the detergent or
      lipid environment. Unlabeled betagamma reconstituted in biotinylated phospholipid
      vesicles (pure phosphatidylcholine or mixed brain lipids) bound F-alpha
      approximately 2-3-fold less tightly (Kd = 6-9 nM) than in Lubrol. In contrast,
      beta gamma in ionic detergents such as cholate and 3
      [(cholamidopropyl)diethylammonio]-1-propanesulfonate exhibited substantially
      lower affinities for F-alpha. Dissociation of F-alpha from beta gamma
      reconstituted in lipid vesicles was observed upon addition of aluminum fluoride
      or excess unlabeled alpha subunit, indicating that myristoylated alpha subunit
      has only a weak interaction with lipids without the beta gamma subunit. The
      kinetics of aluminum fluoride-stimulated dissociation were slower than those of
      the alpha subunit conformational change detected by intrinsic fluorescence. These
      results quantitatively demonstrate G protein subunit dissociation upon activation
      and provide a simple but powerful new approach for studying high affinity
      protein/protein interactions in solution or in a lipid environment.

PMID- 9525891
TI  - Members of the meis1 and pbx homeodomain protein families cooperatively bind a
      cAMP-responsive sequence (CRS1) from bovine CYP17.
AB  - The mammalian Pbx homeodomain proteins provide specificity and increased DNA
      binding affinity to other homeodomain proteins. A cAMP-responsive sequence (CRS1)
      from bovine CYP17 has previously been shown to be a binding site for Pbx1. A
      member of a second mammalian homeodomain family, Meis1, is now also demonstrated
      to be a CRS1-binding protein upon purification using CRS1 affinity
      chromatography. CRS1 binding complexes from Y1 adrenal cell nuclear extract
      contain both Pbx1 and Meis1. This is the first transcriptional regulatory element
      reported as a binding site for members of the Meis1 homeodomain family. Pbx1 and
      Meis1 bind cooperatively to CRS1, whereas neither protein can bind this element
      alone. Mutagenesis of the CRS1 element indicates a binding site for Meis1
      adjacent to the Pbx site. All previously identified Pbx binding partners have Pbx
      interacting motifs that contain a tryptophan residue amino-terminal to the
      homeodomain that is required for cooperative binding to DNA with Pbx. Members of
      the Meis1 family contain one tryptophan residue amino-terminal to the
      homeodomain, but site-directed mutagenesis indicates that this residue is not
      required for cooperative CRS1 binding with Pbx. Thus, the Pbx-Meis1 interaction
      is unique among Pbx complexes. Meis1 also cooperatively binds CRS1 with the Pbx
      homologs extradenticle from Drosophila melanogaster and ceh-20 from
      Caenorhabditis elegans, indicating that this interaction is evolutionarily
      conserved. Thus, CYP17 CRS1 is a transcriptional regulatory element containing
      both Pbx and Meis1 binding sites, which permit these two homeodomain proteins to
      bind and potentially regulate cAMP-dependent transcription through this sequence.

PMID- 9525892
TI  - Thermodynamic evidence for conformational coupling between the B and C domains of
      the mannitol transporter of escherichia coli, enzyme IImtl.
AB  - The transport across the cytoplasmic membrane and concomitant phosphorylation of
      mannitol in Escherichia coli is catalyzed by the mannitol-specific transport
      protein from the phosphoenolpyruvate-dependent phosphotransferase system, enzyme
      IImtl. Interactions between the cytoplasmic B and the membrane embedded C domain
      play an important role in the catalytic cycle of this enzyme, but the nature of
      this interaction is largely unknown. We have studied the thermodynamics of
      binding of (i) mannitol to enzyme IImtl, (ii) the substrate analog perseitol to
      enzyme IImtl, (iii) perseitol to phosphorylated enzyme IImtl, and (iv) mannitol
      to enzyme IImtl treated with trypsin to eliminate the cytoplasmic domains.
      Analysis of the heat capacity increment of these reactions showed that
      approximately 50-60 residues are involved in the binding of mannitol and
      perseitol, but far less in the phosphorylated state or after removal of the B
      domain. A model is proposed in which binding of mannitol leads to the formation
      of a contact interface between the two domains, either by folding of unstructured
      parts or by docking of preexisting surfaces, thus positioning the incoming
      mannitol close to the phosphorylation site on the B domain to facilitate the
      transfer of the phosphoryl group.

PMID- 9525893
TI  - The particulate methane monooxygenase from methylococcus capsulatus (Bath) is a
      novel copper-containing three-subunit enzyme. Isolation and characterization.
AB  - The particulate methane monooxygenase (pMMO) is known to be very difficult to
      study mainly due to its unusual activity instability in vitro. By cultivating
      Methylococcus capsulatus (Bath) under methane stress conditions and high copper
      levels in the growth medium, membranes highly enriched in the pMMO with
      exceptionally stable activity can be isolated from these cells. Purified and
      active pMMO can be subsequently obtained from these membrane preparations using
      protocols in which an excess of reductants and anaerobic conditions were
      maintained during membrane solubilization by dodecyl beta-D-maltoside and
      purification by chromatography. The pMMO was found to be the major constituent in
      these membranes, constituting 60-80% of total membrane proteins. The dominant
      species of the pMMO was found to consist of three subunits, alpha, beta, and
      gamma, with an apparent molecular mass of 45, 26, and 23 kDa, respectively. A
      second species of the pMMO, a proteolytically processed version of the enzyme,
      was found to be composed of three subunits, alpha', beta, and gamma, with an
      apparent molecular mass of 35, 26, and 23 kDa, respectively. The alpha and alpha'
      subunits from these two forms of the pMMO contain identical N-terminal sequences.
      The gamma subunit, however, exhibits variation in its N-terminal sequence. The
      pMMO is a copper-containing protein only and shows a requirement for Cu(I) ions.
      Approximately 12-15 Cu ions per 94-kDa monomeric unit were observed. The pMMO is
      sensitive to dioxygen tension. On the basis of dioxygen sensitivity, three
      kinetically distinct forms of the enzyme can be distinguished. A slow but air
      stable form, which is converted into a "pulsed" state upon direct exposure to
      atmospheric oxygen pressure, is considered as type I pMMO. This form was the
      subject of our pMMO isolation effort. Other forms (types II and III) are
      deactivated to various extents upon exposure to atmospheric dioxygen pressure.
      Under inactivating conditions, these unstable forms release protons to the buffer
      (approximately 10 H+/94-kDa monomeric unit) and eventually become completely
      inactive.

PMID- 9525894
TI  - Specific interaction of HIV-1 and HIV-2 surface envelope glycoproteins with
      monolayers of galactosylceramide and ganglioside GM3.
AB  - Cellular glycosphingolipids mediate the fusion between some viruses and the
      plasma membrane of target cells. In the present study, we have analyzed the
      interaction of human immunodeficiency virus (HIV)-1 and HIV-2 surface envelope
      glycoproteins from distinct viral isolates with monolayers of various
      glycosphingolipids at the air-water interface. The penetration of the viral
      glycoproteins into glycosphingolipid monolayers was detected as an increase in
      the surface pressure. We found that HIV-1 recombinant gp120 (IIIB isolate) could
      penetrate into a monomolecular film of alpha-hydroxylated galactosylceramide
      (GalCer-HFA), while ceramides, GluCer, and nonhydroxylated GalCer were totally
      inactive. The glycoproteins isolated from HIV-1 isolates LAI and NDK and from HIV
      2(ROD) could also interact with a GalCer-HFA monolayer, whereas gp120 from HIV
      1(SEN) and HIV-1(89.6) did not react. These data correlated with the ability of
      the corresponding viruses to gain entry into the CD4(-)/GalCer+ cell line HT-29,
      demonstrating the determinant role of GalCer-HFA in this CD4-independent pathway
      of HIV-1 and HIV-2 infection. In contrast, all HIV-1 and HIV-2 glycoproteins
      tested were found to interact with a monolayer of GM3, a ganglioside abundantly
      expressed in the plasma membrane of CD4(+) lymphocytes and macrophages. A V3 loop
      derived synthetic peptide inhibitor of HIV-1 and HIV-2 infection in both CD4(-)
      and CD4(+) cells could penetrate into various glycosphingolipid monolayers,
      including GalCer-HFA and GM3. Taken together, these data suggest that the
      adsorption of human immunodeficiency viruses to the surface of target cells
      involves an interaction between the V3 domain of the surface envelope
      glycoprotein and specific glycosphingolipids, i.e. GalCer-HFA for CD4(-) cells
      and GM3 for CD4(+) cells.

PMID- 9525895
TI  - Processing and function of a polyprotein precursor of two mitochondrial proteins
      in neurospora crassa.
AB  - In Neurospora crassa, the mitochondrial arginine biosynthetic enzymes, N
      acetylglutamate kinase (AGK) and N-acetyl-gamma-glutamyl-phosphate reductase
      (AGPR), are generated by processing of a 96-kDa cytosolic polyprotein precursor
      (pAGK-AGPR). The proximal kinase and distal reductase domains are separated by a
      short connector region. Substitutions of arginines at positions -2 and -3
      upstream of the N terminus of the AGPR domain or replacement of threonine at
      position +3 in the mature AGPR domain revealed a second processing site at
      position -20. Substitution of arginine at position -22, in combination with
      changes at -2 and -3, prevented cleavage of the precursor and identified two
      proteolytic cleavage sites, Arg-Gly downward arrow Tyr-Leu-Thr at the N terminus
      of the AGPR domain and Arg-Gly-Tyr downward arrow Ser-Thr located 20 residues
      upstream. Inhibitors of metal-dependent peptidases blocked proteolytic cleavage
      at both sites. Amino acid residues required for proteolytic cleavage in the
      connector were identified, and processing was abolished by mutations changing
      these residues. The unprocessed AGK-AGPR fusion had both catalytic activities,
      including feedback inhibition of AGK, and complemented AGK-AGPR- mutants. These
      results indicate that cleavage of pAGK-AGPR is not required for functioning of
      these enzymes in the mitochondria.

PMID- 9525897
TI  - Phosphorylation of an N-terminal motif enhances DNA-binding activity of the human
      SRY protein.
AB  - Of the several strategies that eukaryotes have evolved to modulate transcription
      factor activity, phosphorylation is regarded as one of the major mechanisms in
      signal-dependent transcriptional control. To conclusively demonstrate that the
      human sex-determining gene SRY is affected by such a post-translational control
      mechanism, we have analyzed its phosphorylation status in living cells. In the
      present study, we show that the cyclic AMP-dependent protein kinase (PKA)
      phosphorylates the human SRY protein in vitro as well as in vivo on serine
      residues located in the N-terminal part of the protein. This phosphorylation
      event was shown to positively regulate SRY DNA-binding activity and to enhance
      the ability of SRY to inhibit a basal promoter activity located downstream of an
      SRY DNA-binding site concatamer. Together these results strongly support the
      hypothesis that human SRY is a natural substrate for PKA in vivo and that this
      phosphorylation significantly modulates its major activity, DNA-binding, thereby
      possibly altering its biological function.

PMID- 9525896
TI  - Integrin activation by dithiothreitol or Mn2+ induces a ligand-occupied
      conformation and exposure of a novel NH2-terminal regulatory site on the beta1
      integrin chain.
AB  - Integrins can be expressed in at least three functional states (i.e. latent,
      active, and ligand-occupied). However, the molecular bases for the transitions
      between these states are unknown. In the present study, changes in the
      accessibility of several beta1 epitopes (e.g. N29, B44, and B3B11) were used to
      probe activation-related conformational changes. Dithiothreitol or Mn2+
      activation of integrin-mediated adhesion in the human B cell line, IM9, resulted
      in a marked increase in the exposure of the B44 epitope, while N29 expression
      levels were most sensitive to dithiothreitol treatment. These results contrasted
      with the epitope expression patterns of spontaneously adherent K562 cells, where
      N29 was almost fully accessible and B44 was low. Addition of a soluble ligand
      resulted in a marked increase in B44 levels, suggesting that this antibody
      detected a ligand-induced binding site. The N29 epitope was mapped to a cysteine
      rich region near the NH2 terminus of the integrin chain, thus defining a novel
      regulatory site. These studies indicate that the activation of integrin function
      by different stimuli may involve related but nonidentical conformations. Both
      Mn2+ and dithiothreitol appear to induce localized conformational changes that
      mimic a ligand-occupied receptor. This differs from the "physiologically"
      activated integrins on K562 cells that display a marked increase in overall
      epitope accessibility without exposure of the ligand-induced binding site
      epitopes. The increased exposure of the N29 site on K562 cells may indicate a
      role for this region in the regulation of integrin function.

PMID- 9525898
TI  - Evidence against the Bm1P1 protein as a positive transcription factor for
      barbiturate-mediated induction of cytochrome P450BM-1 in bacillus megaterium.
AB  - The Bm1P1 protein was previously proposed to act as a positive transcription
      factor involved in barbiturate-mediated induction of cytochrome P450BM-1 in
      Bacillus megaterium. We now report that the bm1P1 gene encodes a protein of 217
      amino acids, rather than the 98 amino acids as reported previously. In vitro gel
      shift assays indicate that the Bm1P1 protein did not interact with probes
      comprising the regulatory regions of the P450BM-1 gene. Moreover, disruption of
      the bm1P1 gene did not markedly affect barbiturate induction of P450BM-1
      expression. A multicopy plasmid harboring only the P450BM-1 promoter region could
      increase expression of the chromosome-encoded P450BM-1. The level of expression
      is comparable with that shown by a multicopy plasmid harboring the P450BM-1
      promoter region along with the bm1P1 gene. These results strongly suggest that
      the Bm1P1 protein is unlikely to act as a positive regulator for barbiturate
      induction of P450BM-1 expression. Finally, deletion of the Barbie box did not
      markedly diminish the effect of pentobarbital on expression of a reporter gene
      transcriptionally fused to the P450BM-1 promoter. This suggests that the Barbie
      box is unlikely to be a key element in barbiturate-mediated induction of P450BM
      1.

PMID- 9525899
TI  - Differences in activity between alpha and beta type I interferons explored by
      mutational analysis.
AB  - Type I interferon (IFN) subtypes alpha and beta share a common multicomponent,
      cell surface receptor and elicit a similar range of biological responses,
      including antiviral, antiproliferative, and immunomodulatory activities. However,
      alpha and beta IFNs exhibit key differences in several biological properties. For
      example, IFN-beta, but not IFN-alpha, induces the association of tyrosine
      phosphorylated receptor components ifnar1 and ifnar2, and has activity in cells
      lacking the IFN receptor-associated, Janus kinase tyk2. To define the structural
      basis for these functional differences we produced human IFN-beta with point
      mutations and compared them to wild-type IFN-beta in assays that distinguish
      alpha and beta IFN subtypes. IFN-beta mutants with charged residues (N86K, N86E,
      or Y92D) introduced at two positions in the C helix lost the ability to induce
      the association of tyrosine-phosphorylated receptor chains and had reduced
      activity on tyk2-deficient cells. The combination of negatively charged residues
      N86E and Y92D (homologous with IFN-alpha8) increased the cross-species activity
      of the mutant IFN-betas on bovine cells to a level comparable to that of human
      IFN-alphas. In contrast, point mutations in the AB loop and D helix had no
      significant effect on these subtype-specific activities. A subset of these latter
      mutations did, however, reduce activity in a manner analogous to IFN-alpha
      mutations. The effects of these mutations on IFN-beta activity are discussed in
      the context of a family of related ligands acting through a common receptor and
      signaling pathway.

PMID- 9525900
TI  - Diversity of HIV-1 Vpr interactions involves usage of the WXXF motif of host cell
      proteins.
AB  - Targeting protein or RNA moieties to specific cellular compartments may enhance
      their desired functions and specificities. Human immunodeficiency virus type I
      (HIV-1) encodes proteins in addition to Gag, Pol, and Env that are packaged into
      virus particles. One such retroviral-incorporated protein is Vpr, which is
      present in all primate lentiviruses. Vpr has been implicated in different roles
      within the HIV-1 life cycle. In testing a new hypothesis in which viral proteins
      are utilized as docking sites to incorporate protein moieties into virions, we
      used the peptide phage display approach to search for Vpr-specific binding
      peptides. In the present studies, we demonstrate that most of the peptides that
      bind to Vpr have a common motif, WXXF. More importantly, we demonstrate that the
      WXXF motif of uracil DNA glycosylase is implicated in the interaction of uracil
      DNA glycosylase with Vpr intracellularly. Finally, a dimer of the WXXF motif was
      fused to the chloramphenicol acetyl transferase (CAT) gene, and it was
      demonstrated that the WXXF dimer-CAT fusion protein construct produces CAT
      activity within virions in the presence of Vpr as a docking protein. This study
      provides a novel potential strategy in the targeting of anti-viral agents to
      interfere with HIV-1 replication.

PMID- 9525903
TI  - An acyl-CoA synthase (acoas) gene adjacent to the mycocerosic acid synthase (mas)
      locus is necessary for mycocerosyl lipid synthesis in Mycobacterium tuberculosis
      var. bovis BCG.
AB  - An open reading frame, ORF3, first identified adjacent to the mycocerosic acid
      synthase gene in Mycobacterium bovis BCG encodes a protein with acyl-CoA synthase
      (ACoAS) activity. Genes homologous to acoas are found adjacent to other
      multifunctional polyketide synthase genes in the mycobacterial genome. To test
      whether these gene products are necessary to esterify the fatty acids generated
      by the adjacent polyketide synthase gene products, the acoas gene was disrupted
      in M. bovis BCG using a suicide vector containing the acoas gene with an internal
      deletion and the hygromycin-resistant gene as selection marker. Allelic exchange
      at the acoas locus was confirmed by Southern hybridization and polymerase chain
      reaction amplification of both flanking regions expected from homologous
      recombination. Immunoblot analysis indicated that the 65-kDa ACoAS protein
      product was absent in the mutant. Chromatographic analysis of lipids derived from
      [1-14C]propionate showed that the mutant did not produce mycocerosyl lipids,
      although it produced normal levels of mycocerosic acid synthase. These results
      suggest that ACoAS is involved in the synthesis of mycocerosyl lipids of the
      mycobacterial cell wall.

PMID- 9525904
TI  - Sorting of D-lactate dehydrogenase to the inner membrane of mitochondria.
      Analysis of topogenic signal and energetic requirements.
AB  - D-Lactate dehydrogenase (D-LD) is located in the inner membrane of mitochondria.
      It spans the membrane once in an Nin-Cout orientation with the bulk of the
      protein residing as a folded domain in the intermembrane space. D-LD is
      synthesized as a precursor with an N-terminal cleavable presequence and is
      imported into the mitochondria in a Deltapsi-dependent, but mt-Hsp70-independent
      manner. Upon import in vitro D-LD folds in the intermembrane space to attain a
      conformation indistinguishable from endogenous D-LD. Sorting of D-LD to the inner
      membrane is directed by a composite topogenic signal consisting of the
      hydrophobic transmembrane segment and a cluster of charged amino acids C-terminal
      to it. We propose a model for the mode of operation of the sorting signal of D
      LD. This model also accounts for the driving force of translocation across the
      outer membrane, in the apparent absence of mt-Hsp70-dependent assisted import and
      involves the folding of the D-LD in the intermembrane space.

PMID- 9525901
TI  - Expression of CD38 increases intracellular calcium concentration and reduces
      doubling time in HeLa and 3T3 cells.
AB  - CD38 is a bifunctional ectoenzyme, predominantly expressed on hematopoietic cells
      during differentiation, that catalyzes the synthesis (cyclase) and the
      degradation (hydrolase) of cyclic ADP-ribose (cADPR), a powerful calcium
      mobilizer from intracellular stores. Due to the well established role of calcium
      levels in the regulation of apoptosis, proliferation, and differentiation, the
      CD38/cADPR system seems to be a likely candidate involved in the control of these
      fundamental processes. The ectocellular localization of the cyclase activity,
      however, contrasts with the intracellular site of action of cADPR. Here we
      demonstrate that ectocellular expression of human CD38 in CD38(-) HeLa and 3T3
      cells results in intracellular CD38 substrate (NAD+ + NADH) consumption and
      product (cADPR) accumulation. Furthermore, a causal relationship is established
      between presence of intracellular cADPR, partial depletion of thapsigargin
      sensitive calcium stores, increase in basal free cytoplasmic calcium
      concentration, and decrease of cell doubling time. The significant shortening of
      the S phase in CD38(+) HeLa cells, as compared with controls, demonstrates an
      effect of intracellular cADPR on the mammalian cell cycle.

PMID- 9525902
TI  - Role of semicarbazide-sensitive amine oxidase on glucose transport and GLUT4
      recruitment to the cell surface in adipose cells.
AB  - The previous characterization of an abundant population of non-adrenergic
      imidazoline-I2 binding sites in adipocytes and the recent demonstration of the
      interplay between these binding sites and amine oxidases led us to analyze the
      amine oxidase activity in membranes from isolated rat adipocytes. Adipocyte
      membranes had substantial levels of semicarbazide-sensitive amine oxidase (SSAO).
      SSAO activity and immunoreactive SSAO protein were maximal in plasma membranes,
      and they were also detectable in intracellular membranes. Vesicle immunoisolation
      analysis indicated that GLUT4-containing vesicles from rat adipocytes contain
      substantial levels of SSAO activity and immunoreactive SSAO protein.
      Immunotitration of intracellular GLUT4 vesicles indicated that GLUT4 and SSAO
      colocalize in an endosomal compartment in rat adipocytes. SSAO activity was also
      found in GLUT4 vesicles from 3T3-L1 adipocytes and rat skeletal muscle.
      Benzylamine, a substrate of SSAO activity, caused a marked stimulation of glucose
      transport in isolated rat adipocytes in the presence of very low vanadate
      concentrations that by themselves were ineffective in exerting insulin-like
      effects. This synergistic effect of benzylamine and vanadate on glucose transport
      was totally abolished in the presence of semicarbazide, a specific inhibitor of
      SSAO. Subcellular membrane fractionation revealed that the combination of
      benzylamine and vanadate caused a recruitment of GLUT4 to the plasma membrane of
      adipose cells. The stimulatory effects of benzylamine and vanadate on glucose
      transport were blocked by catalase, suggesting that hydrogen peroxide production
      coupled to SSAO activity plays a crucial regulatory role. Based on these results
      we propose that SSAO activity might contribute through hydrogen peroxide
      production to the in vivo regulation of GLUT4 trafficking in adipose cells.

PMID- 9525905
TI  - Role of reactive oxygen intermediates in activation-induced CD95 (APO-1/Fas)
      ligand expression.
AB  - Activation-induced cell death of T lymphocytes requires the inducible expression
      of CD95 (APO-1/Fas) ligand, which triggers apoptosis in CD95-bearing target cells
      by an autocrine or paracrine mechanism. Although execution of the CD95 death
      pathway is largely independent of reactive oxygen intermediates, activation
      induced cell death is blocked by a variety of antioxidants. In the present study,
      we investigated the involvement of redox processes in the regulation of CD95
      ligand (CD95L) expression in Jurkat T cells. We show that various antioxidants
      potently inhibited the transcriptional activation of CD95L following T cell
      receptor ligation or stimulation of cells with phorbol ester and ionomycin.
      Conversely, a prooxidant such as hydrogen peroxide alone was able to increase
      CD95L expression. As detected by Western blot and cytotoxicity assays, functional
      expression of CD95L protein was likewise diminished by antioxidants. Inhibition
      of CD95L expression was associated with a decreased DNA binding activity of
      nuclear factor (NF)-kappaB, an important redox-controlled transcription factor.
      Moreover, inhibition of NF-kappaB activity by a transdominant IkappaB mutant
      attenuated CD95L expression. Our data suggest that, although reactive oxygen
      intermediates do not act as mediators in the execution phase of CD95-mediated
      apoptosis, they are involved in the transcriptional regulation of CD95L
      expression.

PMID- 9525906
TI  - A conformational B-cell epitope on the C-terminal end of the extracellular part
      of human thyroid peroxidase.
AB  - To investigate the B-cell autoimmune epitopes on human thyroid peroxidase (TPO),
      we generated proteolytic peptides by enzymatic hydrolysis of TPO in nondenaturing
      and nonreducing conditions. The hydrolysate was chromatographed on a reverse
      phase column. We eluted a material immunoreactive with both a TPO monoclonal
      antibody recognizing a linear epitope (mAb47, amino acid 713-721) and TPO
      autoantibodies (aAb) from patients. The aAb immunoreactivity, but not that of
      mAb47, was lost after reduction. Western blots after electrophoresis without
      reduction showed that the aAb and mAb47 were immunoreactive with a 66-kDa band
      and that aAb identified a doublet at 20 kDa. For electrophoresis under reducing
      conditions, the 66-kDa band resolved into two peptides of 40 and 26 kDa, whereas
      the doublet at 20 kDa remained unchanged. None of these reduced peptides was
      immunoreactive with aAb, whereas the 40-kDa peptide was immunoreactive with
      mAb47. The 40-kDa peptide extends from amino acid 549 to 933 of TPO, and its last
      192 amino acids overlap the autoimmune 20-kDa peptide. After iodine labeling, the
      20-kDa peptide lost its immunoreactivity. We conclude that the C-terminal end of
      the extracellular part of TPO, which includes all the tyrosine residues of the 20
      kDa peptide, contains at least one conformational B-cell epitope involved in
      autoimmune thyroid diseases.

PMID- 9525907
TI  - Characterization of graf, the GTPase-activating protein for rho associated with
      focal adhesion kinase. Phosphorylation and possible regulation by mitogen
      activated protein kinase.
AB  - Graf is a GTPase-activating protein for Rho that interacts with focal adhesion
      kinase and co-localizes with the actin cytoskeleton (Hildebrand, J. D., Taylor,
      J. M. and Parsons, J. T. (1996) Mol. Cell. Biol. 16, 3169-3178). We examined the
      expression and regulation of Graf as a prelude to understanding the role of Graf
      in mediating signal transduction in vivo. We demonstrated that Graf is a
      ubiquitously expressed 95-kDa protein with high levels observed in heart and
      brain and cells derived from these tissues. Stimulation of PC12 cells with
      epidermal growth factor or nerve growth factor induced a phosphatase-reversible
      mobility shift upon gel electrophoresis, indicative of phosphorylation. In vitro,
      purified mitogen-activated protein (MAP) kinase catalyzed the phosphorylation of
      Graf on serine 510, suggesting that Graf phosphorylation may be mediated through
      MAP kinase signaling. In addition, the mutation of serine 510 to alanine
      inhibited the epidermal growth factor-induced mobility shift of mutant Graf
      protein in vivo, consistent with serine 510 being the site of in vivo
      phosphorylation. Based on these data we suggest that phosphorylation of Graf by
      MAP kinase or related kinases may be a mechanism by which growth factor signaling
      modulates Rho-mediated cytoskeletal changes in PC12 and perhaps other cells.

PMID- 9525909
TI  - Structural and functional effects of pseudo-module substitution in hemoglobin
      subunits. New structural and functional units in globin structure.
AB  - Functional and structural significance of the "module" in proteins has been
      investigated for globin proteins. Our previous studies have revealed that some
      modules in globins are responsible for regulating the subunit association and
      heme environmental structures, whereas the module substitution often induces
      fatal structural destabilization, resulting in failure of functional regulation.
      In this paper, to gain further insight into functional and structural
      significance of the modular structure in globins, we focused upon the "pseudo
      module" in globin structure where boundaries are located at the center of
      modules. Although the pseudo-module has been supposed not to retain a
      compactness, the betaalpha(PM3)-subunit, in which one of the pseudo-modules, the
      F1-H6 region, of the alpha-subunit is implanted into the beta-subunit, conserved
      stable globin structure, and its association property was converted into that of
      the alpha-subunit, as the case for the module substituted globin, the
      betaalpha(M4)-subunit. These results suggest that modules are not unique
      structural and functional units for globins. Interestingly, however, the recent
      reconsideration of the module boundary indicates that the modules in globins can
      be further divided into two small modules, and one of the boundaries for the new
      small modules coincides with that of the pseudo-module we substituted in this
      study. Although it would be premature to conclude the significance of the modular
      structure in globins, it can be safely said that we have found new structural
      units in globin structure, probably new modules.

PMID- 9525908
TI  - Differential regulation of human neutrophil FcgammaRIIa (CD32) and FcgammaRIIIb
      (CD16)-induced Ca2+ transients.
AB  - Human neutrophils express two structurally distinct receptors for the Fc region
      of IgG, FcgammaRIIa and FcgammaRIIIb. Although earlier studies have suggested
      that the functional properties of these receptors are similar, mounting evidence
      suggests that these receptors are capable of inducing distinct functional
      responses. Accordingly, we have examined the regulation of intracellular Ca2+
      transients induced by each of these receptors alone (homotypic receptor cross
      linking) and together (heterotypic receptor cross-linking). The
      glycosylphosphatidylinositol-anchored FcgammaRIIIb induces a rise in [Ca2+] after
      homotypic cross-linking that is independent of ligand-mediated engagement of the
      transmembrane FcgammaRIIa. Both receptors were sensitive to the protein-tyrosine
      kinase inhibitor methyl 2,5-dihydroxycinnamate, but FcgammaRIIa-induced signaling
      was uniquely sensitive to the protein-tyrosine kinase inhibitor genistein.
      FcgammaRIIa but not FcgammaRIIIb engages a cAMP-sensitive and inositol 1,4, 5
      trisphosphate-dependent pathway(s) that results in the Ca2+-transient. When these
      receptors are cross-linked into heterotypic clusters, a synergistic rise in
      [Ca2+] is observed that is accompanied by synergistic increases in the
      phospholipase Cgamma-breakdown products inositol 1,4,5-trisphosphate and
      diglyceride. These data provide a mechanism for the functional differences
      between these two receptors and suggest the possibility that they can be
      differentially modulated.

PMID- 9525910
TI  - In vivo and in vitro regulation of hepatic glucagon receptor mRNA concentration
      by glucose metabolism.
AB  - We have recently cloned the murine glucagon receptor (GR) gene and shown that it
      is expressed mainly in liver. In this organ, the glucagon-GR system is involved
      in the control of glucose metabolism as it initiates a cascade of events leading
      to release of glucose into the blood stream, which is a main feature in several
      physiological and pathological conditions. To better define the metabolic
      regulators of GR expression in liver we analyzed GR mRNA concentration in
      physiological conditions associating various glucose metabolic pathways in vivo
      and in vitro in the rat and in the mouse. First, we report that the concentration
      of the GR mRNA progressively increased from the first day of life to the adult
      stage. This effect was abolished when newborn rodents were fasted. Second, under
      conditions where intrahepatic glucose metabolism was active such as during
      fasting, diabetes, and hyperglycemic clamp, the concentration of GR mRNA
      increased independent of the origin of the pathway that generated the glucose
      flux. These effects were blunted when hyperglycemia was corrected by phlorizin
      treatment of diabetic rats or not sustained during euglycemic clamp. In
      accordance with these observations, we demonstrated that the glycolytic
      substrates glucose, mannose, and fructose, as well as the gluconeognic substrates
      glycerol and dihydroxyacetone, increased the concentration of GR mRNA in primary
      cultures of hepatocytes from fed rats. Glucagon blunted the effect of glucose
      without being dominant. The stimulatory effect of those substrates was not
      mimicked by the nonmetabolizable carbohydrate L-glucose or the glucokinase
      inhibitor glucosamine or when hepatocytes were isolated from starved rats. In
      addition, inhibitors of gluconeogenesis and lipolysis could decrease the
      concentration of GR mRNA from hepatocytes of starved rats. Combined, these data
      strongly suggest that glucose flux in the glycolytic and gluconeogenic pathways
      at the level of triose intermediates could control expression of GR mRNA and
      participate in controlling its own metabolism.

PMID- 9525911
TI  - Mitochondrial NADH-ubiquinone oxidoreductase (Complex I). Effect of substrates on
      the fragmentation of subunits by trypsin.
AB  - It has been shown that treatment of bovine mitochondrial complex I (NADH
      ubiquinone oxidoreductase) with NADH or NADPH, but not with NAD or NADP,
      increases the susceptibility of a number of subunits to tryptic degradation. This
      increased susceptibility involved subunits that contain electron carriers, such
      as FMN and iron-sulfur clusters, as well as subunits that lack electron carriers.
      Results shown elsewhere on changes in the cross-linking pattern of complex I
      subunits when the enzyme was pretreated with NADH or NADPH (Belogrudov, G., and
      Hatefi, Y. (1994) Biochemistry 33, 4571-4576) also indicated that complex I
      undergoes extensive conformation changes when reduced by substrate. Furthermore,
      we had previously shown that in submitochondrial particles the affinity of
      complex I for NAD increases by >/=20-fold in electron transfer from succinate to
      NAD when the particles are energized by ATP hydrolysis. Together, these results
      suggest that energy coupling in complex I may involve protein conformation
      changes as a key step. In addition, it has been shown here that treatment of
      complex I with trypsin in the presence of NADPH, but not NADH or NAD(P), produced
      from the 39-kDa subunit a 33-kDa degradation product that resisted further
      hydrolysis. Like the 39-kDa subunit, the 33-kDa product bound to a NADP-agarose
      affinity column, and could be eluted with a buffer containing NADPH. It is
      possible that together with the acyl carrier protein of complex I the NADP(H)
      binding 39-kDa subunit is involved in intramitochondrial fatty acid synthesis.

PMID- 9525912
TI  - Coenzyme Q6 and iron reduction are responsible for the extracellular ascorbate
      stabilization at the plasma membrane of Saccharomyces cerevisiae.
AB  - Yeast plasma membrane contains an electron transport system that maintains
      ascorbate in its reduced form in the apoplast. Reduction of ascorbate free
      radical by this system is comprised of two activities, one of them dependent on
      coenzyme Q6 (CoQ6). Strains with defects in CoQ6 synthesis exhibit decreased
      capacity for ascorbate stabilization compared with wild type or with atp2 or cor1
      respiratory-deficient mutant strains. Both CoQ6 content in plasma membranes and
      ascorbate stabilization were increased during log phase growth. The addition of
      exogenous CoQ6 to whole cells resulted in its incorporation in the plasma
      membrane, produced levels of CoQ6 in the coq3 mutant strain that were 2-fold
      higher than in the wild type, and increased ascorbate stabilization activity in
      both strains, although it was higher in the coq3 mutant than in wild type. Other
      antioxidants, such as benzoquinone or alpha-tocopherol, did not change ascorbate
      stabilization. The CoQ6-independent reduction of ascorbate free radical was not
      due to copper uptake, pH changes or to the presence of CoQ6 biosynthetic
      intermediates, but decreased to undetectable levels when coq3 mutant strains were
      cultured in media supplemented with ferric iron. Plasma membrane CoQ6 levels were
      unchanged by either the presence or absence of iron in wild type, atp2, or cor1
      strains. Ascorbate stabilization appears to be a function of the yeast plasma
      membrane, which is partially based on an electron transfer chain in which CoQ6 is
      the central electron carrier, whereas the remainder is independent of CoQ6 and
      other antioxidants but is dependent on the iron-regulated ferric reductase
      complex.

PMID- 9525913
TI  - Increased activity of a novel low pH folate transporter associated with
      lipophilic antifolate resistance in chinese hamster ovary cells.
AB  - Previous studies described a Chinese hamster ovary cell line, PyrR100, resistant
      to lipid-soluble antifolates due to the loss of an energy-coupled folate exporter
      resulting in a marked increase in intracellular folate cofactor accumulation.
      There was, in addition, an unexplained increase in folic acid influx in PyrR100
      cells which is shown in this paper to be mediated by a transporter with a low pH
      optimum. The pH profile for folic acid influx in parental Chinese hamster ovary
      AA8 cells indicated peak activity at pH 6; this was increased >3-fold in PyrR100
      cells. In contrast, methotrexate (MTX) influx in AA8 cells showed two peaks of
      comparable activities at pH 6 and 7.5; in PyrR100 cells, the component at pH 6
      was increased 2-fold. Folic acid was a potent inhibitor of [3H]MTX or [3H]folic
      acid influx (1 microM) via the low pH route with IC50 values of approximately 1
      microM. Prostaglandin A1 was a potent inhibitor of [3H]MTX influx via the reduced
      folate carrier 1 at pH 7.5 with only a small inhibitory effect on the low pH
      route. The addition of 10 microM folic acid to PyrR100 cells resulted in a MTX
      influx pH profile identical to that of AA8 cells, consistent with suppression of
      the low pH route. In contrast, addition of 25 microM prostaglandin A1 to PyrR100
      cells resulted in a MTX influx pH profile comparable to that of folic acid,
      consistent with the loss of the reduced folate carrier-mediated component.
      Inhibition ( approximately 70%) of [3H]folic acid influx by approximately 10
      microM unlabeled folic acid at pH 7.5 indicated that the low pH transporter
      accounts for the majority of folic acid transport at physiological pH. This study
      demonstrates the functional importance of a low pH folate transporter that is
      increased when enhanced folic acid entry into cells is required as an adaptive
      response to antifolate selective pressure. This may represent a mechanism of
      resistance to new antifolate inhibitors of folate cofactor-dependent enzymes in
      which cytotoxic activity is limited by expanded cellular folate pools.

PMID- 9525914
TI  - Purification and characterization of a GDP-fucose:polypeptide fucosyltransferase
      from Chinese hamster ovary cells.
AB  - A GDP-fucose:polypeptide fucosyltransferase was purified 5000-fold to homogeneity
      from Chinese hamster ovary cell extracts in the absence of detergent. The
      purification procedure included two affinity chromatographic steps using the
      acceptor substrate, a recombinant factor VII EGF-1 domain, and the donor
      substrate analog, GDP-hexanolamine, as ligands. The purified enzyme migrates as a
      single band of 44,000 daltons on SDS-polyacrylamide gel electrophoresis and is
      itself a glycoprotein with more than one high mannose type oligosaccharide chain
      with a total molecular weight of 4000. The Km values for factor VII EGF-1 domain
      and GDP-fucose are 15 and 6 microM, respectively. The Vmax is 2.5 micromol.min
      1.mg-1. The presence of 50 mM Mn2+ increased the enzyme activity 17-fold, but
      Mn2+ was not absolutely required, since the enzyme exhibited some activity even
      in the presence of EDTA. The acceptor substrate specificity was studied using
      site-directed mutagenesis of human factor IX EGF domain. Only one of several
      differently folded species could serve as acceptor substrate, although they all
      had the same molecular weight as determined by liquid chromatography on-line with
      mass spectrometry. This indicates that the enzyme requires proper folding of the
      epidermal growth factor domain for its activity.

PMID- 9525915
TI  - Aging-related deficiency of CD28 expression in CD4+ T cells is associated with
      the loss of gene-specific nuclear factor binding activity.
AB  - Changes in T cell populations and concomitant perturbation of T cell effector
      functions have been postulated to account for many aging-related immune
      dysfunctions. Here, we report that high frequencies of CD28(null) CD4+ T cells
      were found in elderly individuals. Because deviations in the function of these
      unusual CD4+ T cells might be directly related to CD28 deficiency, we examined
      the molecular basis for the loss of CD28 expression in CD4+ T cells. In reporter
      gene bioassays, the minimal promoter of the CD28 gene was mapped to the proximal
      400 base pairs (bp) of the 5' untranslated region. CD28 deficiency was associated
      with the loss of two noncompeting binding activities within a 67-bp segment of
      the minimal promoter. These binding activities were not competed by consensus
      Ets, Elk, or AP3 motifs that were found within the sequence stretch. The DNA
      protein complexes were also not recognized by antibodies to Ets-related
      transcription factors. Furthermore, introduction of mutations into the 67-bp
      segment at positions corresponding to the two DNA-protein interaction sites, i.e.
      nucleotides spanning -206 to -179 and -171 to -148, resulted in the loss of
      specific nuclear factor binding activities and the abrogation of promoter
      activity. These observations implicate at least two regulatory motifs in the
      constitutive expression of CD28. The loss of binding activity of trans-acting
      factors specific for these sequences may contribute to the accumulation
      CD4+CD28(null) T cells during aging.

PMID- 9525916
TI  - HIV-1 Tat elongates the G1 phase and indirectly promotes HIV-1 gene expression in
      cells of glial origin.
AB  - Human immunodeficiency virus type-1 (HIV-1) infection of the central nervous
      system (CNS) gives rise to many of the neurological complications in patients
      with AIDS. Infection of microglial cells and astrocytes in the brain promotes the
      release of HIV-1 Tat and other candidate neurotoxins that may be associated with
      the widespread neuropathology. To examine the contribution of HIV-1 Tat to the
      interplay between virus and CNS cells, the human astrocytic cell line, U-87MG,
      was treated with recombinant Tat protein. Fluorescence-activated cell sorting
      analysis indicated that Tat induces a G1 arrest in these cells. Consistent with
      this observation, lower levels of cyclin E-Cdk2 kinase activity and
      phosphorylated Rb were detected in the Tat-treated cells compared with the
      control cells. Interestingly, our observations indicate that the
      underphosphorylated form of Rb that is prevalent in Tat-treated cells promotes
      HIV-1 transcription by a mechanism involving the NF-kappaB enhancer region. Taken
      together, the data presented here provide the first evidence that the HIV-1
      regulatory protein, Tat, may manipulate the host cell cycle to promote viral gene
      expression. The significance of these findings relates to the current hypothesis
      that indirect effects of HIV-1 infection of the CNS may contribute to the
      neurological complications associated with AIDS dementia complex.

PMID- 9525918
TI  - Unusual charge stabilization of NADP+ in 17beta-hydroxysteroid dehydrogenase.
AB  - Type 1 17beta-hydroxysteroid dehydrogenase (17beta-HSD1), a member of the short
      chain dehydrogenase reductase (SDR) family, is responsible for the synthesis of
      17beta-estradiol, the biologically active estrogen involved in the genesis and
      development of human breast cancers. Here, we report the crystal structures of
      the H221L 17beta-HSD1 mutant complexed to NADP+ and estradiol and the H221L
      mutant/NAD+ and a H221Q mutant/estradiol complexes. These structures provide a
      complete picture of the NADP+-enzyme interactions involving the flexible 191-199
      loop (well ordered in the H221L mutant) and suggest that the hydrophobic residues
      Phe192-Met193 could facilitate hydride transfer. 17beta-HSD1 appears to be unique
      among the members of the SDR protein family in that one of the two basic residues
      involved in the charge compensation of the 2'-phosphate does not belong to the
      Rossmann-fold motif. The remarkable stabilization of the NADP+ 2'-phosphate by
      the enzyme also clearly establishes its preference for this cofactor relative to
      NAD+. Analysis of the catalytic properties of, and estradiol binding to, the two
      mutants suggests that the His221-steroid O3 hydrogen bond plays an important role
      in substrate specificity.

PMID- 9525917
TI  - A GTPase-independent mechanism of p21-activated kinase activation. Regulation by
      sphingosine and other biologically active lipids.
AB  - p21-activated kinases (PAKs) are serine/threonine kinases that have been
      identified as targets for the small GTPases Rac and Cdc42. PAKs have been
      implicated in cytoskeletal regulation, stimulation of mitogen-activated protein
      kinase cascades, and in control of the phagocyte NADPH oxidase. Membrane
      targeting of PAK1 induced increased kinase activity in a GTPase-independent
      manner, suggesting that other mechanisms for PAK regulation exist. We observed
      concentration- and time-dependent activation of PAK1 by sphingosine and several
      related long chain sphingoid bases but not by ceramides or a variety of other
      lipids. Although phospholipids were generally ineffective, phosphatidic acid and
      phosphatidylinositol also had stimulatory effects on PAK1. Lipid stimulation
      induced a similar level of PAK1 activity as did stimulation by GTPases, and the
      patterns of PAK1 autophosphorylation determined after partial tryptic digestion
      and two-dimensional peptide analysis were similar with each class of activator.
      Lipid stimulation of PAK1 activity was dependent upon intact PAK kinase activity,
      as indicated by studies with a kinase-dead PAK1 mutant. Treatment of COS-7 cells
      expressing wild type PAK1 with sphingosine, fumonisin B, or sphingomyelinase, all
      of which are able to elevate the levels of free sphingosine, induced increased
      activity of PAK1 as determined using a p47(phox) peptide substrate. Studies using
      PAK1 mutants suggest that lipids act at a site overlapping or identical to the
      GTPase-binding domain on PAK. The inactive sphingosine derivative N,N
      dimethylsphingosine was an effective inhibitor of PAK1 activation in response to
      either sphingosine or Cdc42. Our results demonstrate a novel GTPase-independent
      mechanism of PAK activation and, additionally, suggest that PAK(s) may be
      important mediators of the biological effects of sphingolipids.

PMID- 9525919
TI  - Identification of binding sites for bepridil and trifluoperazine on cardiac
      troponin C.
AB  - The solution structure of cardiac troponin C (cTnC) (Sia, S., Li, M. X.,
      Spyracopoulos, L., Gagne, S. M., Liu, W., Putkey, J. A. & Sykes, B. D. (1997) J.
      Biol. Chem. 272, 18216-18221) challenges existing structure/function models for
      this critical regulatory protein. For example, it is clear that the closed
      conformation of the regulatory N-terminal domain in Ca2+-bound cardiac troponin C
      (cTnC) presents a much different binding surface for Ca2+-sensitizing compounds
      than previously thought. We report here the use of Met methyl groups as site
      specific structural markers to identify drug binding sites for trifluoperazine
      and bepridil on cTnC. Drug dependent changes in the NMR heteronuclear single
      quantum coherence spectra of [methyl-13C]Met-labeled cTnC indicate that bepridil
      and trifluoperazine bind to similar sites but only in the presence of Ca2+. There
      are 3-4 drug binding sites in the N- and C-terminal domains of intact cTnC that
      exhibit fast exchange on the NMR time scale. Use of a novel spin-labeled
      phenothiazine and detection of isotope-filtered nuclear Overhauser effects
      allowed identification of drug binding sites in the shallow hydrophobic cup in
      the C-terminal domain and on two hydrophobic surfaces on the N-terminal
      regulatory domain. The data presented here, coupled with our previous study using
      covalent blocking groups, support a model in which the Ca2+-sensitizing binding
      site includes Met-45 in helix B of site I, and Met-60 and -80 in helices B and C
      of the regulatory site II. This subregion in cTnC makes a likely target against
      which to design new and selective Ca2+-sensitizing compounds.

PMID- 9525920
TI  - Cell density sensing mediated by a G protein-coupled receptor activating
      phospholipase C.
AB  - When the unicellular eukaryote Dictyostelium discoideum starves, it senses the
      local density of other starving cells by simultaneously secreting and sensing a
      glycoprotein called conditioned medium factor (CMF). When the density of starving
      cells is high, the corresponding high density of CMF permits signal transduction
      through cAR1, the chemoattractant cAMP receptor. cAR1 activates a heterotrimeric
      G protein whose alpha-subunit is Galpha2. CMF regulates cAMP signal transduction
      in part by regulating the lifetime of the cAMP-stimulated Galpha2-GTP
      configuration. We find here that guanosine 5'-3-O-(thio)triphosphate (GTPgammaS)
      inhibits the binding of CMF to membranes, suggesting that the putative CMF
      receptor is coupled to a G protein. Cells lacking Galpha1 (Galpha1 null) do not
      exhibit GTPgammaS inhibition of CMF binding and do not exhibit CMF regulation of
      cAMP signal transduction, suggesting that the putative CMF receptor interacts
      with Galpha1. Work by others has suggested that Galpha1 inhibits phospholipase C
      (PLC), yet when cells lacking either Galpha1 or PLC were starved at high cell
      densities (and thus in the presence of CMF), they developed normally and had
      normal cAMP signal transduction. We find that CMF activates PLC. Galpha1 null
      cells starved in the absence or presence of CMF behave in a manner similar to
      control cells starved in the presence of CMF in that they extend pseudopods, have
      an activated PLC, have a low cAMP-stimulated GTPase, permit cAMP signal
      transduction, and aggregate. Cells lacking Gbeta have a low PLC activity that
      cannot be stimulated by CMF. Cells lacking PLC exhibit IP3 levels and cAMP
      stimulated GTP hydrolysis rates intermediate to what is observed in wild-type
      cells starved in the absence or in the presence of an optimal amount of CMF. We
      hypothesize that CMF binds to its receptor, releasing Gbetagamma from Galpha1.
      This activates PLC, which causes the Galpha2 GTPase to be inhibited, prolonging
      the lifetime of the cAMP-activated Galpha2-GTP configuration. This, in turn,
      allows cAR1-mediated cAMP signal transduction to take place.

PMID- 9525921
TI  - Perturbation of dynamin II with an amphiphysin SH3 domain increases GLUT4 glucose
      transporters at the plasma membrane in 3T3-L1 adipocytes. Dynamin II participates
      in GLUT4 endocytosis.
AB  - The GLUT4 glucose transporter continuously recycles between the cell surface and
      an endosomal compartment in adipocytes. Insulin decreases the rate of GLUT4
      endocytosis in addition to increasing its exocytosis. Endocytosis of the
      transporter is thought to occur at least in part via the clathrin-mediated
      endocytic system. The protein dynamin is involved in the final stages of clathrin
      coated vesicle formation. Here we show that the dynamin II isoform is expressed
      in 3T3-L1 adipocytes and is present in isolated plasma membrane and low density
      microsomal fractions. Insulin reduced the levels of dynamin II associated with
      the plasma membrane by about half, raising the possibility that the hormone may
      reduce GLUT4 endocytosis by removing dynamin from the cell surface. A fusion
      protein containing the amphiphysin SH3 domain selectively bound dynamin II from
      3T3-L1 adipocyte cell lysates. Microinjection of the fusion protein into these
      cells inhibited transferrin endocytosis and increased the levels of GLUT4 at the
      cell surface. Glutathione S-transferase alone, the SH3 domains of spectrin and
      Crk, and a mutated amphiphysin SH3 domain unable to bind dynamin II did not
      affect GLUT4 distribution. However, a peptide containing the dynamin II sequence
      that binds amphiphysin increased the surface presence of GLUT4. Moreover, in
      cells first treated with insulin to externalize GLUT4, the dynamin peptide, but
      not an unrelated control peptide, inhibited GLUT4 internalization upon insulin
      removal. These results suggest that interactions of dynamin II with amphiphysin
      may play an important role in GLUT4 endocytosis. We hypothesize that insulin may
      reduce GLUT4 endocytosis by regulating the function of dynamin II at the cell
      surface, as part of the mechanism to increase glucose uptake.

PMID- 9525922
TI  - Intracellular localization of the 74- and 53-kDa forms of L-histidine
      decarboxylase in a rat basophilic/mast cell line, RBL-2H3.
AB  - To clarify the process of post-translational modification of L-histidine
      decarboxylase (HDC), we investigated the conversion of the 74-kDa form of HDC
      into the 53-kDa form in specialized organella of a rat basophilic/mast cell line
      (RBL-2H3). With treatment of streptolysin-O, RBL-2H3 cells released approximately
      40% of HDC activity accompanied by over 90% of lactate dehydrogenase activity.
      Only the 74-kDa form of HDC was detected in the leaked fraction by SDS
      polyacrylamide gel electrophoresis. The 74-kDa form in the homogenate of pulse
      labeled cells was recovered in both the supernatant and particulate fractions,
      while the 53-kDa form was detected only in the particulate fraction containing
      marker proteins of microsomes, Golgi, and lysosomal granules. Confocal
      microscopic observation using double staining immunofluorescence with anti-GST
      fusion HDC antiserum showed that most of the HDC coexists with protein-disulfide
      isomerase, a typical marker of the luminal space of the ER. With treatment of
      digitonin, RBL-2H3 cells released only 74-kDa HDC. Trypsin digestion of digitonin
      permeabilized cells resulted in the disappearance of the 74-kDa form but not the
      53-kDa form. From these results, it is assumed that the 74-kDa form of HDC,
      synthesized in the cytosol, is translocated into the lumen of the ER, where it is
      converted to the 53-kDa form.

PMID- 9525923
TI  - Matrin CYP, an SR-rich cyclophilin that associates with the nuclear matrix and
      splicing factors.
AB  - We report the identification and cloning of a nuclear matrix protein termed
      matrin cyclophilin or matrin CYP. The derived sequence of matrin cyp encodes a
      protein of 752 amino acids with a predicted mass of 88 kDa. A 172-residue stretch
      at the amino terminus shows high identity with the ubiquitous family of
      cyclophilins. Clustered throughout the carboxyl half of the protein are a series
      of serine-arginine (SR) repeats that are a characteristic feature of many RNA
      splicing factors. Antibodies raised against matrin CYP recognize a 106-kDa
      antigen that is detected in isolated nuclei and quantitatively subfractionates in
      the nuclear matrix. Laser scanning confocal microscopy localizes most of the anti
      matrin CYP-specific antigen within the nucleus in a pattern of large bright
      speckles that co-localize with splicing factors and diffuse nucleoplasmic
      staining. A strikingly similar pattern of staining is observed in cells extracted
      for in situ nuclear matrices. A fusion protein containing the cyclophilin domain
      of matrin CYP exhibits cyclosporin A (CsA)-sensitive, peptidylprolyl cis-trans
      isomerase activity that is characteristic of native cyclophilins. Although total
      rat liver nuclei contains predominantly CsA-resistant PPIase activity, the
      corresponding activity in the nuclear matrix is largely CsA-sensitive.

PMID- 9525924
TI  - Molecular cloning of human GDP-mannose 4,6-dehydratase and reconstitution of GDP
      fucose biosynthesis in vitro.
AB  - We have cloned the cDNA encoding human GDP-mannose 4,6-dehydratase, the first
      enzyme in the pathway converting GDP-mannose to GDP-fucose. The message is
      expressed in all tissues and cell lines examined, and the cDNA complements Lec13,
      a Chinese Hamster Ovary cell line deficient in GDP-mannose 4,6-dehydratase
      activity. The human GDP-mannose 4,6-dehydratase polypeptide shares 61% identity
      with the enzyme from Escherichia coli, suggesting broad evolutionary
      conservation. Purified recombinant enzyme utilizes NADP+ as a cofactor and, like
      its E. coli counterpart, is inhibited by GDP-fucose, suggesting that this aspect
      of regulation is also conserved. We have isolated the product of the dehydratase
      reaction, GDP-4-keto-6-deoxymannose, and confirmed its structure by electrospray
      ionization-mass spectrometry and high field NMR. Using purified recombinant human
      GDP-mannose 4,6-dehydratase and FX protein (GDP-keto-6-deoxymannose 3,5
      epimerase, 4-reductase), we show that the two proteins alone are sufficient to
      convert GDP-mannose to GDP-fucose in vitro. This unequivocally demonstrates that
      the epimerase and reductase activities are on a single polypeptide. Finally, we
      show that the two homologous enzymes from E. coli are sufficient to carry out the
      same enzymatic pathway in bacteria.

PMID- 9525925
TI  - The role of calcium and phosphorylation of cytosolic phospholipase A2 in
      regulating arachidonic acid release in macrophages.
AB  - Arachidonic acid release is induced in macrophages with diverse agonists
      including calcium ionophores, phorbol myristate acetate (PMA), okadaic acid, and
      the phagocytic particle, zymosan, and correlates with activation of cytosolic
      phospholipase A2 (cPLA2). The role of calcium and phosphorylation of cPLA2 in
      regulating arachidonic acid release was investigated. Zymosan induced a rapid and
      transient increase in [Ca2+]i. This in itself is not sufficient to induce
      arachidonic acid release since ATP and platelet activating factor (PAF), agonists
      that induce transient calcium mobilization in macrophages, induced little
      arachidonic acid release. Unlike zymosan, which is a strong activator of mitogen
      activated protein kinase (MAPK), ATP and PAF were weak MAPK activators and
      induced only a partial and transient increase in cPLA2 phosphorylation (gel
      shift). However, ATP or PAF together with colony stimulating factor-1 (CSF-1)
      synergistically stimulated arachidonic acid release. CSF-1 is a strong MAPK
      activator that induces a rapid and complete cPLA2 gel shift but not calcium
      mobilization or arachidonic acid release. Arachidonic acid release was more rapid
      in response to CSF-1 plus ATP or PAF than zymosan and correlated with the time
      course of the cPLA2 gel shift. Although low concentrations of ionomycin induced a
      lower magnitude of calcium mobilization than ATP, the response was more sustained
      resulting in arachidonic acid release. A23187 and ionomycin induced weak MAPK
      activation, and a partial and transient cPLA2 gel shift. The MAPK kinase
      inhibitor, PD 98059 suppressed A23187-induced MAPK activation and cPLA2 gel shift
      but had little effect on arachidonic acid release. These results indicate that in
      macrophages a transient increase in [Ca2+]i and sustained phosphorylation of
      cPLA2 can act together to promote arachidonic acid release but neither alone is
      sufficient. A sustained increase in calcium is sufficient for inducing
      arachidonic acid release. However, PMA and okadaic acid induce arachidonic acid
      release without increasing [Ca2+]i, although resting levels of calcium are
      required, suggesting alternative mechanisms of regulation.

PMID- 9525926
TI  - Improved fluorescence and dual color detection with enhanced blue and green
      variants of the green fluorescent protein.
AB  - The green fluorescent protein (GFP) from the jellyfish Aequorea victoria is a
      versatile reporter protein for monitoring gene expression and protein
      localization in a variety of systems. Applications using GFP reporters have
      expanded greatly due to the availability of mutants with altered spectral
      properties, including several blue emission variants, all of which contain the
      single point mutation Tyr-66 to His in the chromophore region of the protein.
      However, previously described "BFP" reporters have limited utility, primarily due
      to relatively dim fluorescence and low expression levels attained in higher
      eukaryotes with such variants. To improve upon these qualities, we have combined
      a blue emission mutant of GFP containing four point mutations (Phe-64 to Leu, Ser
      65 to Thr, Tyr-66 to His, and Tyr-145 to Phe) with a synthetic gene sequence
      containing codons preferentially found in highly expressed human proteins. These
      mutations were chosen to optimize expression of properly folded fluorescent
      protein in mammalian cells cultured at 37 degreesC and to maximize signal
      intensity. The combination of improved fluorescence and higher expression levels
      yield an enhanced blue fluorescent protein that provides greater sensitivity and
      is suitable for dual color detection with green-emitting fluorophores.

PMID- 9525927
TI  - Prevention of mitochondrial injury by manganese superoxide dismutase reveals a
      primary mechanism for alkaline-induced cell death.
AB  - Alkalosis is a clinical complication resulting from various pathological and
      physiological conditions. Although it is well established that reducing the
      cellular proton concentration is lethal, the mechanism leading to cell death is
      unknown. Mitochondrial respiration generates a proton gradient and superoxide
      radicals, suggesting a possible link between oxidative stress, mitochondrial
      integrity, and alkaline-induced cell death. Manganese superoxide dismutase
      removes superoxide radicals in mitochondria, and thus protects mitochondria from
      oxidative injury. Cells cultured under alkaline conditions were found to exhibit
      elevated levels of mitochondrial membrane potential, reactive oxygen species, and
      calcium which was accompanied by mitochondrial damage, DNA fragmentation, and
      cell death. Overexpression of manganese superoxide dismutase reduced the levels
      of intracellular reactive oxygen species and calcium, restored mitochondrial
      transmembrane potential, and prevented cell death. The results suggest that
      mitochondria are the primary target for alkaline-induced cell death and that free
      radical generation is an important and early event conveying cell death signals
      under alkaline conditions.

PMID- 9525928
TI  - Sp1 sites mediate activation of the plasminogen activator inhibitor-1 promoter by
      glucose in vascular smooth muscle cells.
AB  - This study was designed to characterize the direct effects of hyperglycemia on
      plasminogen activator inhibitor-1 (PAI-1) expression in cultured vascular smooth
      muscle cells. Glucose induced dose- and time-dependent increases of PAI-1 mRNA
      expression in rat aortic smooth muscle (RASM) cells in vitro. Using a series of
      luciferase reporter gene constructs containing PAI-1 5'-flanking sequence (from 
      6.4 kilobase to -42 base pairs (bp)) transfected into RASM, we found that glucose
      (25 mM) consistently induced a 4-fold increase in luciferase activity, with the
      response localized to sequence between -85 and -42 bp. Mutagenesis of two
      putative Sp1-binding sites located in the region of interest essentially
      obliterated the glucose-response. Electrophoretic mobility shift assays with
      radiolabeled oligonucleotides containing the two putative Sp1-binding sites from
      PAI-1 promoter and nuclear extracts from RASM cells revealed that glucose
      treatment markedly changed the mobility pattern of the major protein-DNA
      complexes. Supershift assay showed that transcription factor Sp1 was present in
      the complexes under control and hyperglycemic conditions. These results suggest
      that glucose regulates PAI-1 gene expression in RASM cells through an effect on
      two adjacent Sp1 sites located between -85 and -42 bp of the PAI-1 5'-flanking
      region and that the release of a transcriptional repressor from the Sp1 complexes
      may explain the activation of the PAI-1 gene under high glucose conditions in
      RASM cells.

PMID- 9525929
TI  - MKK6 activates myocardial cell NF-kappaB and inhibits apoptosis in a p38 mitogen
      activated protein kinase-dependent manner.
AB  - In cardiac myocytes the stimulation of p38 mitogen-activated protein kinase
      activates a hypertrophic growth program and the induction of the cardiac-specific
      genes associated with this program. This study focused on determining whether
      these novel growth-promoting effects are accompanied by the p38-mediated
      inhibition of apoptosis, and if so, what signaling pathways might be responsible.
      Primary neonatal rat ventricular myocytes were driven into apoptosis by
      treatments known to induce apoptosis in other cell types, e.g. incubation with
      anisomycin or overexpression constitutively active MEKK-1 (MEKK-1COOH), a protein
      that strongly activates extracellular signal-regulated kinase and N-terminal c
      Jun kinase, but not p38. Overexpression of constitutively active MKK6, MKK6
      (Glu), which selectively activates p38 in cardiac myocytes, protected cells from
      either anisomycin- or MEKK-1COOH-induced apoptosis. This protection was blocked
      by SB 203580, a selective p38 inhibitor. MKK6 (Glu) also activated transcription
      mediated by NF-kappaB, a factor which protects other cell types from apoptosis.
      The activation of NF-kappaB and the protection from apoptosis mediated by MKK6
      (Glu) were both blocked by SB 203580. Interestingly, overexpression of a mutant
      form of I-kappaBalpha, which inhibits nuclear translocation of NF-kappaB,
      completely blocked MKK6 (Glu)-activated NF-kappaB but had little effect on MKK6s
      anti-apoptotic effects. These findings suggest that, in part, the overexpression
      of MKK6 (Glu) may foster growth and survival of cardiac myocytes by protecting
      them from apoptosis in a p38-dependent manner. Additionally, while NF-kappaB is
      activated in myocardial cells by p38, this does not appear to be the major
      mechanism by which MKK6 (Glu) exerts its anti-apoptotic effects in this cell
      type, suggesting a novel pathway for p38-mediated protection from apoptosis.

PMID- 9525930
TI  - The cyclic adenosine monophosphate-dependent protein kinase (PKA) is required for
      the sustained activation of mitogen-activated kinases and gene expression by
      nerve growth factor.
AB  - Induction of neuronal differentiation of the rat pheochromocytoma cell line, PC12
      cells, by nerve growth factor (NGF) requires activation of the mitogen-activated
      protein (MAP) kinase or extracellular signal-regulated kinase (ERK). cAMP
      dependent protein kinase (protein kinase A (PKA)) also can induce differentiation
      of these cells. Like NGF, the ability of PKA to differentiate PC12 cells is
      associated with a sustained activation of ERKs. Here we show that maximal
      sustained activation of ERK1 by NGF requires PKA. Inhibitors of PKA partially
      blocked activation of ERK1 by NGF but had no effect on activation of ERK1 by EGF.
      Inhibition of PKA also reduced the ability of NGF and cAMP, but not EGF, to
      activate the transcription factor Elk-1, reduced the induction of both immediate
      early and late genes after NGF treatment, and blocked the nuclear translocation
      of ERK1 induced by NGF. We propose that PKA is an important contributor to the
      activation of ERK1 by NGF and is required for maximal induction of gene
      expression by NGF.

PMID- 9525931
TI  - Sites of volatile anesthetic action on kainate (Glutamate receptor 6) receptors.
AB  - Molecular mechanisms of anesthetic action on neurotransmitter receptors are
      poorly understood. The major excitatory neurotransmitter in the central nervous
      system is glutamate, and recent studies found that volatile anesthetics inhibit
      the function of the alpha-amino-3-hydroxyisoxazolepropionic acid subtype of
      glutamate receptors (e.g. glutamate receptor 3 (GluR3)), but enhance kainate
      (GluR6) receptor function. We used this dissimilar pharmacology to identify sites
      of anesthetic action on the kainate GluR6 receptor by constructing chimeric
      GluR3/GluR6 receptors. Results with chimeric receptors implicated a transmembrane
      region (TM4) of GluR6 in the action of halothane. Site-directed mutagenesis
      subsequently showed that a specific amino acid, glycine 819 in TM4, is important
      for enhancement of receptor function by halothane (0. 2-2 mM). Mutations of Gly
      819 also markedly decreased the response to isoflurane (0.2-2 mM), enflurane (0.2
      2 mM), and 1-chloro-1,2, 2-trifluorocyclobutane (0.2-2 mM). The nonanesthetics 1,
      2-dichlorohexafluorocyclobutane and 2,3-dichlorooctafluorobutane had no effect on
      the functions of either wild-type GluR6 or receptors mutated at Gly-819. Ethanol
      and pentobarbital inhibited the function of both wild-type and mutant receptors.
      These results suggest that a specific amino acid, Gly-819, is critical for the
      action of volatile anesthetics, but not of ethanol or pentobarbital, on the GluR6
      receptor.

PMID- 9525933
TI  - cDNA cloning and expression of a family of UDP-N-acetyl-D
      galactosamine:polypeptide N-acetylgalactosaminyltransferase sequence homologs
      from Caenorhabditis elegans.
AB  - The initiation of mucin-type O-glycosylation is catalyzed by a family of UDP
      GalNAc:polypeptide N-acetylgalactosaminyltransferases (ppGaNTase) (EC 2.4.1.41).
      By screening two mixed-stage Caenorhabditis elegans cDNA libraries, a total of 11
      distinct sequence homologs of the ppGaNTase gene family were cloned, sequenced,
      and expressed as truncated recombinant proteins (gly-3, gly-4, gly-5a, gly-5b,
      gly-5c, gly-6a, gly-6b, gly-6c, gly-7, gly-8, and gly-9). All clones encoded type
      II membrane proteins that shared 60-80% amino acid sequence similarity with the
      catalytic domain of mammalian ppGaNTase enzymes. Two sets of cDNA clones (gly-5
      and gly-6) contained variants that appeared to be produced by alternative message
      processing. gly-6c contained a reading frameshift and premature termination codon
      in the C-terminal lectin-like domain found in most other ppGaNTase proteins, and
      a second clone (gly-8) lacked the typical C-terminal region completely.
      Homogenates of nematodes and immunopurified preparations of the recombinant GLY
      proteins demonstrated that worms express functional ppGaNTase enzymes (GLY-3, GLY
      4, GLY-5A, GLY-5B, and GLY-5C), which can O-glycosylate mammalian apomucin
      peptide sequences in vitro. In addition to demonstrating the existence of
      ppGaNTase enzymes in a nematode organism, the substantial diversity of these
      isoforms in C. elegans suggests that mucin O-glycosylation is catalyzed by a
      complex gene family, which is conserved among evolutionary-distinct organisms.

PMID- 9525932
TI  - Distinct membrane and cytosolic forms of inositol polyphosphate 5-phosphatase II.
      Efficient membrane localization requires two discrete domains.
AB  - The 75-kDa inositol polyphosphate 5-phosphatase (5-phosphatase II) hydrolyzes
      various signaling molecules including the following: inositol 1,4,5
      trisphosphate, inositol 1,3,4,5-tetrakisphosphate, phosphatidylinositol 4,5
      bisphosphate, and phosphatidylinositol 3,4, 5-trisphosphate. Although studied
      extensively, a demonstrably full-length cDNA encoding 5-phosphatase II has yet to
      be isolated. In this study we used a human partial 2.3-kilobase pair (kb) cDNA to
      screen mouse brain and kidney cDNA libraries, resulting in the isolation of a 3.7
      kb cDNA (M5), which by multiple criteria represents a full-length cDNA encoding a
      115-kDa 5-phosphatase II. We also isolated a smaller cDNA (M22) with a unique N
      terminus that encodes a 104-kDa polypeptide. Analysis of these cDNAs suggests a
      further 87-kDa isoform may arise from differential splicing resulting in
      translation at methionine 234 in M5. RNA analysis of tissues demonstrates
      expression of two mRNA species of approximately 4.0 or 3.0 kb, respectively.
      Probes unique to the 5' end of M5 or M22 hybridized to the 4.0- or 3.0-kb
      transcripts, respectively. RNA analysis using probes derived from sequence 3' to
      the potential splice site in M5 and M22 hybridized to both transcripts.
      Expression of the recombinant 115-kDa protein, or a smaller recombinant protein
      lacking the N terminus transiently in COS-7 cells, showed localization of enzyme
      activity to the membrane. Removal of the C-terminal CAAX motif resulted in a
      significant translocation of the protein lacking the N terminus but not the 115
      kDa 5-phosphatase to the cytosol. Western blot analysis of membrane and cytosolic
      fractions of multiple mouse tissues confirmed the 115-kDa 5-phosphatase II was
      located in the membrane, whereas the 104- and 87-kDa isoforms were prominent in
      the cytosol. Collectively these studies demonstrate the widespread expression of
      at least three isoforms of 5-phosphatase II derived from RNA splicing events.
      This allows differential distribution of the 5-phosphatase II activity between
      the membrane and cytosol of the cell and thereby may regulate enzyme access to
      phosphoinositide-derived signaling molecules.

PMID- 9525934
TI  - Lymphoid-specific expression of the Id3 gene in hematopoietic cells. Selective
      antagonism of E2A basic helix-loop-helix protein associated with Id3-induced
      differentiation of erythroleukemia cells.
AB  - Accumulating evidence implicates functions of the Id family of helix-loop-helix
      proteins in the regulation of cell growth and differentiation in metazoa. Within
      the mammalian hematopoietic organ, expression of the Id3 gene is restricted to
      the lymphoid cell compartment. We show here that in non-lymphoid hematopoietic
      cells, repression of transcription is correlated with hypermethylation of
      sequences in the vicinity of the upstream regulatory region of the Id3 gene,
      suggestive of a strict developmental control of expression of this gene in
      lymphoid versus non-lymphoid hematopoietic cells. Enforced ectopic expression of
      Id3 in K562 erythroid progenitor cells promotes erythroid differentiation and is
      correlated with a quantitative/qualitative shift in the profile of interacting
      TAL1 and E protein heterodimers that bind to a consensus E box sequence in in
      vitro band shift assays, consistent with selective targeting of E2A E protein(s)
      by Id3 and suggesting a possible mechanism involving TAL1-mediated
      differentiation. By using a Gal 4-VP16 two-hybrid competition assay and an E box
      dependent reporter assay, we demonstrate directly that the E2A protein E47
      preferentially associates with Id3 in vivo. These observations provide a paradigm
      for understanding how overlapping but distinct specificities of individual Id
      proteins may constitute a developmentally regulated program underlying cell
      determination in diverse lineages.

PMID- 9525935
TI  - Regulation of human B19 parvovirus promoter expression by hGABP (E4TF1)
      transcription factor.
AB  - The genetic expression of human B19 parvovirus is only dependent on one promoter
      in vivo and in vitro. This is the P6 promoter, which is located on the left side
      of the genome and is a single-stranded DNA molecule. This led us to investigate
      the regulation of the P6 promoter and the possible resulting variability of the
      nucleotide sequence. After analysis of the promoter region of 17 B19 strains,
      only 1.5% variability was found. More exciting was the finding of mutations that
      were clustered around the TATA box and defined a highly conserved region
      (nucleotides 113-210) in the proximal part of the P6 promoter. HeLa and UT7/Epo
      cell extracts were found to protect this region, which contained a core motif for
      Ets family proteins, with YY1 and Sp1 binding sites on either side. Gel mobility
      shift assays performed with nuclear proteins from HeLa and UT7/Epo cells
      identified DNA-binding proteins specific for these sites. By supershift analysis,
      we demonstrated the binding of the hGABP (also named E4TF1) protein to the Ets
      binding site and the fixation of Sp1 and YY1 proteins on their respective motifs.
      In Drosophila SL2 cells, hGABPalpha and -beta stimulated P6 promoter activity,
      and hGABPalpha/hGABPbeta and Sp1 exerted synergistic stimulation of this
      activity, an effect diminished by YY1.

PMID- 9525936
TI  - Cooperative binding properties of restriction endonuclease EcoRII with DNA
      recognition sites.
AB  - EcoRII is a member of the expanding group of type IIe restriction endonucleases
      that share the distinguishing feature of requiring cooperativity between two
      recognition sites in their substrate DNA. To determine the stoichiometry of the
      active DNA-enzyme complex and the mode of cooperative interaction, we have
      investigated the dependence of EcoRII cleavage on the concentration of EcoRII
      dimers. Maximal restriction was observed at dimer/site ratios of 0.25 and 0. 5.
      The molecular weight of the DNA-enzyme complex eluted from a gel filtration
      column also corresponds to a dimeric enzyme structure bound to two substrate
      sites. We conclude that one EcoRII dimer is sufficient to interact cooperatively
      with two DNA recognition sites. A Lac repressor "barrier" bound between two
      normally reactive EcoRII sites did not inhibit restriction endonuclease activity,
      indicating that cooperativity between EcoRII sites is achieved by bending or
      looping of the intervening DNA stretch. Comparative cleavage of linear substrates
      with differently spaced interacting sites revealed an inverse correlation between
      cleavage rate and site distance. At the optimal distance of one helical turn,
      EcoRII cleavage is independent of the orientation of the recognition sequence in
      the DNA double strand.

PMID- 9525937
TI  - Molecular characterization of a glyoxysomal long chain acyl-CoA oxidase that is
      synthesized as a precursor of higher molecular mass in pumpkin.
AB  - A cDNA clone for pumpkin acyl-CoA oxidase (EC 1.3.3.6; ACOX) was isolated from a
      lambdagt11 cDNA library constructed from poly(A)+ RNA extracted from etiolated
      cotyledons. The inserted cDNA clone contains 2313 nucleotides and encodes a
      polypeptide of 690 amino acids. Analysis of the amino-terminal sequence of the
      protein indicates that the pumpkin acyl-CoA oxidase protein is synthesized as a
      larger precursor containing a cleavable amino-terminal presequence of 45 amino
      acids. This presequence shows high similarity to the typical peroxisomal
      targeting signal (PTS2). Western blot analysis following cell fractionation in a
      sucrose gradient revealed that ACOX is localized in glyoxysomes. A partial
      purification of ACOX from etiolated pumpkin cotyledons indicated that the ACOX
      cDNA codes for a long chain acyl-CoA oxidase. The amount of ACOX increased and
      reached to the maximum activity by day 5 of germination but decreased about 4
      fold on the following days during the subsequent microbody transition from
      glyoxysomes to leaf peroxisomes. By contrast, the amount of mRNA was already high
      at day 1 of germination, increased by about 30% at day 3, and faded completely by
      day 7. These data indicated that the expression pattern of ACOX was very similar
      to that of the glyoxysomal enzyme 3-ketoacyl-CoA thiolase, another marker enzyme
      of the beta-oxidation spiral, during germination and suggested that the
      expression of each enzyme of beta-oxidation is coordinately regulated.

PMID- 9525938
TI  - Evolution of an Escherichia coli protein with increased resistance to oxidative
      stress.
AB  - L-1,2-Propanediol:NAD+ 1-oxidoreductase of Escherichia coli is encoded by the
      fucO gene, a member of the regulon specifying dissimilation of L-fucose. The
      enzyme normally functions during fermentative growth to regenerate NAD from NADH
      by reducing the metabolic intermediate L-lactaldehyde to propanediol which is
      excreted. During aerobic growth L-lactaldehyde is converted to L-lactate and
      thence to the central metabolite pyruvate. The wasteful excretion of propanediol
      is minimized by oxidative inactivation of the oxidoreductase, an Fe2+-dependent
      enzyme which is subject to metal-catalyzed oxidation (MCO). Mutants acquiring the
      ability to grow aerobically on propanediol as sole carbon and energy source can
      be readily selected. These mutants express the fucO gene constitutively, as a
      result of an IS5 insertion in the promoter region. In this study we show that
      continued selection for aerobic growth on propanediol resulted in mutations in
      the oxidoreductase conferring increased resistance to MCO. In two independent
      mutants, the resistance of the protein was respectively conferred by an Ile7 -->
      Leu and a Leu8 --> Val substitution near the NAD-binding consensus amino acid
      sequence. A site-directed mutant protein with both substitutions showed an MCO
      resistance greater than either mutant protein with a single amino acid change.

PMID- 9525939
TI  - The Phe-Met-Arg-Phe-amide-activated sodium channel is a tetramer.
AB  - The Helix aspersa Phe-Met-Arg-Phe-amide (FMRFamide)-gated sodium channel is
      formed by homomultimerization of several FMRFamide-activated Na+ channel (FaNaCh)
      proteins. FaNaCh is homologous to the subunits that compose the amiloride
      sensitive epithelial sodium channel, to Caenorhabditis elegans degenerins, and to
      acid-sensing ionic channels. FaNaCh properties were analyzed in stably
      transfected human embryonic kidney cells (HEK-293). The channel was functional
      with an EC50 for FMRFamide of 1 microM and an IC50 (25 degreesC) for amiloride of
      6.5 microM as assessed by 22Na+ uptake measurements. The channel activity was
      associated with the presence of a protein at the cell surface with an apparent
      molecular mass of 82 kDa. The 82-kDa form was derived from an incompletely
      glycosylated form of 74 kDa found in the endoplasmic reticulum. Formation of
      covalent bonds between subunits of the same complex were observed either after
      formation of intersubunit disulfide bonds following cell homogenization and
      solubilization with Triton X-100 or after use of bifunctional cross-linkers. This
      resulted in the formation of covalent multimers that contained up to four
      subunits. Hydrodynamic properties of the solubilized FaNaCh complex also
      indicated a maximal stoichiometry of four subunits per complex. It is likely that
      epithelial Na+ channels, acid-sensing ionic channels, degenerins, and the other
      proteins belonging to the same ion channel superfamily also associate within
      tetrameric complexes.

PMID- 9525941
TI  - Biochemical and molecular characterization of 1-hydroxy-2-naphthoate dioxygenase
      from Nocardioides sp. KP7.
AB  - 1-Hydroxy-2-naphthoate dioxygenase, which cleaves the singly hydroxylated
      aromatic ring, was purified from phenanthrene-degrading Nocardioides sp. strain
      KP7. The purified enzyme had a molecular mass of 45 kDa by SDS-polyacrylamide gel
      electrophoresis and 270 kDa by gel filtration chromatography. The apparent Km and
      kcat values of this enzyme for 1-hydroxy-2-naphthoate were 10 microM and 114 s-1,
      respectively. One mole of molecular oxygen was consumed when 1 mol of 1-hydroxy-2
      naphthoate was oxidized. This enzyme contained 1 mol of Fe(II)/mol of the subunit
      and was inactivated by o-phenanthroline. The enzyme that had been inactivated by
      o-phenanthroline was reactivated by incubating with FeSO4 and ascorbic acid.
      Thus, Fe(II) was required for the enzyme to exhibit activity. The structural gene
      for this enzyme was screened from a cosmid library and then sequenced, the length
      of the 1-hydroxy-2-naphthoate gene being 1161 base pairs. The deduced amino acid
      sequence of this enzyme was different from those of other ring-cleaving
      dioxygenases that cleave the doubly hydroxylated aromatic ring.

PMID- 9525940
TI  - Fyn, Yes, and Syk phosphorylation sites in c-Cbl map to the same tyrosine
      residues that become phosphorylated in activated T cells.
AB  - Protooncogenic protein c-Cbl undergoes tyrosine phosphorylation in response to
      stimulation through the receptors for antigens, immunoglobulins, cytokines, and
      growth factors as well as through the integrins. Tyrosine phosphorylation of c
      Cbl may play a functional role in signal transduction, since c-Cbl interacts with
      many crucial signaling molecules including protein-tyrosine kinases, adaptor
      proteins, and phosphatidylinositol 3'-kinase. Therefore, it is essential for our
      understanding of the functions of c-Cbl in signal transduction to identify its
      tyrosine phosphorylation sites, to determine the protein-tyrosine kinases that
      phosphorylate these sites, and to elucidate the role of these sites in the
      interactions of c-Cbl with other signaling proteins. In this report, we
      demonstrate that tyrosines 700, 731, and 774 are the major tyrosine
      phosphorylation sites of c-Cbl in T cells in response to pervanadate treatment,
      as well as in response to TcR/CD3 ligation. Coexpression experiments in COS cells
      demonstrate that among T cell-expressed Src- and Syk-related protein-tyrosine
      kinases, Fyn, Yes, and Syk appear to play a major role in phosphorylation of c
      Cbl, whereas Lck and Zap phosphorylate c-Cbl ineffectively. Fyn, Yes, and Syk
      phosphorylate the same sites of c-Cbl that become phosphorylated in stimulated T
      cells. Among these kinases, Fyn and Yes demonstrate strong binding to c-Cbl,
      which involves both phosphotyrosine-dependent and phosphotyrosine-independent
      mechanisms.

PMID- 9525942
TI  - Specific binding of phosphatidylinositol 4,5-bisphosphate to calcium-dependent
      activator protein for secretion (CAPS), a potential phosphoinositide effector
      protein for regulated exocytosis.
AB  - The calcium-dependent activator protein for secretion (CAPS) is a novel
      neural/endocrine-specific cytosolic and peripheral membrane protein required for
      the Ca2+-regulated exocytosis of secretory vesicles. CAPS acts at a stage in
      exocytosis that follows ATP-dependent priming, which involves the essential
      synthesis of phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). In the
      present studies, CAPS is shown to bind liposomes that contain acidic
      phospholipids and binding was markedly enhanced by inclusion of PtdIns(4,5)P2 but
      not other phosphoinositides in the absence of Ca2+. PtdIns(4,5)P2, but not other
      phosphoinositides including PtdIns(3, 4)P2 and PtdIns(3,4,5)P3, altered the
      susceptibility of CAPS to proteolysis by trypsin and proteinase K, suggesting
      that phosphoinositide binding promoted a conformational change. Photoaffinity
      labeling studies with a photoactivatable benzoylcinnimidyl acyl chain derivative
      of PtdIns(4,5)P2 confirmed the phosphoinositide-binding properties of CAPS and
      suggested a hydrophobic aspect of the interaction. CAPS, as one of very few
      characterized proteins with a binding specificity for 4-, 5-phosphorylated
      inositides over 3-phosphorylated inositides, may function in regulated exocytosis
      as an effector of PtdIns(4,5)P2.

PMID- 9525943
TI  - Specific interaction of Golgi coatomer protein alpha-COP with
      phosphatidylinositol 3,4,5-trisphosphate.
AB  - The phosphoinositide binding selectivity of Golgi coatomer COPI polypeptides was
      examined using photoaffinity analogs of the soluble inositol polyphosphates
      Ins(1,4,5)P3, Ins(1,3,4,5)P4, and InsP6, and of the polyphosphoinositides
      PtdIns(3,4,5)P3, PtdIns(4,5)P2, and PtdIns(3,4)P2. Highly selective
      Ins(1,3,4,5)P4-displaceable photocovalent modification of the alpha-COP subunit
      was observed with a p-benzoyldihydrocinnamide (BZDC)-containing probe, [3H]BZDC
      Ins(1,3,4,5)P4. A more highly phosphorylated probe, [3H]BZDC-InsP6 probe labeled
      six of the seven subunits, with only beta, beta', delta, and epsilon-COP showing
      competitive displacement by excess InsP6. Importantly, [3H]BZDC-triester
      PtdIns(3,4,5)P3, the lipid with the same phosphorylation pattern as
      Ins(1,3,4,5)P4, showed specific, PtdIns(3,4,5)P3-displaceable labeling of only
      alpha-COP. Labeling by the PtdIns(4,5)P2 and PtdIns(3,4)P2 photoaffinity probes
      was less intense and showed no discrimination based on PtdInsPn ligand. Thus,
      both the D-3 and D-5 phosphates are critical for the alpha-COP-PtdIns(3,4,5)P3
      interaction, suggesting an important role for this polyphosphoinositide in
      vesicular trafficking.

PMID- 9525944
TI  - Diphtheria toxin translocation across endosome membranes. A novel cell
      permeabilization assay reveals new diphtheria toxin fragments in endocytic
      vesicles.
AB  - By using cells overexpressing diphtheria toxin (DT) receptor and a novel method
      of permeabilizing the plasma membrane with a bacterial pore-forming toxin,
      specific translocation of fragment A to the cytosol was observed, whereas full
      size DT and other minor species of DT-derived fragments were left in
      intracellular vesicles. The translocation competence of DT proteins with
      mutations in the transmembrane domain is consistent with their cytotoxicities.
      The charge-reversal mutants E349K and D352K do not translocate their fragment A
      to the cytosol, whereas D352N is partially competent. ADP-ribosyltransferase
      activity of fragment A is not required for translocation. Novel fragments of DT
      with apparent molecular masses of 28 and 35 kDa were detected in endocytic
      vesicles. The 28-kDa fragment consists of fragment A and an N-terminal piece of
      fragment B, whereas the 35-kDa fragment contains part of fragment B and may be
      complementary to the 28-kDa fragment. Time course studies show that the 28-kDa
      fragment appears in endocytic vesicles prior to translocation of fragment A to
      the cytosol, raising the possibility that the 28-kDa fragment is an intermediate
      in translocation. We present a model for translocation of fragment A that
      incorporates the observations made using the novel permeabilization method.

PMID- 9525945
TI  - Selection and analysis of a mutant cell line defective in the hypoxia-inducible
      factor-1 alpha-subunit (HIF-1alpha). Characterization of hif-1alpha-dependent and
      -independent hypoxia-inducible gene expression.
AB  - Hypoxia-inducible expression has been demonstrated for many groups of mammalian
      genes, and studies of transcriptional control have revealed the existence of
      hypoxia-responsive elements (HREs) in the cis-acting sequences of several of
      these genes. These sequences generally contain one or more binding sites for a
      heterodimeric DNA binding complex termed hypoxia-inducible factor-1 (HIF-1). To
      analyze this response further, Chinese hamster ovary cells were stably
      transfected with plasmids bearing HREs linked to genes encoding immunoselectable
      cell surface markers, and clones that showed reduced or absent hypoxia-inducible
      marker expression were selected from a mutagenized culture of cells. Analysis of
      these cells revealed several clones with transacting defects in HRE activation,
      and in one the defect was identified as a failure to express the alpha-subunit of
      HIF-1. Comparison of hypoxia-inducible gene expression in wild type, HIF-1alpha
      defective, and HIF-1alpha-complemented cells revealed two types of response. For
      some genes (e.g. glucose transporter-1), hypoxia-inducible expression was
      critically dependent on HIF-1alpha, whereas for other genes (e.g. heme oxygenase
      1) hypoxia-inducible expression appeared largely independent of the expression of
      HIF-1alpha. These experiments show the utility of mutagenesis and selection of
      mutant cells in the analysis of mammalian transcriptional responses to hypoxia
      and demonstrate the operation of HIF-1alpha-dependent and HIF-1alpha-independent
      pathways of hypoxia-inducible gene expression in Chinese hamster ovary cells.

PMID- 9525946
TI  - Biochemical function of mouse minichromosome maintenance 2 protein.
AB  - Minichromosome maintenance (MCM) proteins play an essential role in eukaryotic
      DNA replication and bind to chromatin before the initiation of DNA replication.
      We reported that MCM protein complexes consisting of MCM2, -4, -6, and -7 bind
      strongly to a histone-Sepharose column (Ishimi, Y., Ichinose, S., Omori, A.,
      Sato, K., and Kimura, H. (1996) J. Biol. Chem. 271, 24115-24122). Here, we have
      analyzed this interaction at the molecular level. We found that among six mouse
      MCM proteins, only MCM2 binds to histone; amino acid residues 63-153 are
      responsible for this binding. The region required for nuclear localization of
      MCM2 was mapped near this histone-binding domain. Far-Western blotting analysis
      of truncated forms of H3 histone indicated that amino acid residues 26-67 of H3
      histone are required for binding to MCM2. We have also shown that mouse MCM2 can
      inhibit the DNA helicase activity of the human MCM4, -6, and -7 protein complex.
      These results suggest that MCM2 plays a different role in the initiation of DNA
      replication than the other MCM proteins.

PMID- 9525947
TI  - A rare 920-kilobase chromosomal inversion mediated by IS1 transposition causes
      constitutive expression of the yiaK-S operon for carbohydrate utilization in
      Escherichia coli.
AB  - The regulator of the yiaK-S operon, currently assigned a carbohydrate utilization
      function in Escherichia coli, is inactivated by a genome rearrangement that leads
      to the constitutive expression of the operon. The yiaK-S constitutive cells
      acquire the ability to utilize the rare pentose L-lyxose. Restriction analysis
      and sequencing of the regulator gene indicate that it is disrupted by foreign
      DNA. The insert consists of a large inverted fragment of DNA of 920 kilobases
      flanked by two IS1 elements with opposite polarity. One corresponds to that found
      naturally at min 0.4 of the bacterial chromosome and the other to a new copy
      transposed into the regulator gene located at min 80.6. This insertion-inversion
      could be the result of the intramolecular transposition mechanism itself, a gene
      rearrangement rarely originated by IS1. Alternatively, it could be attributed to
      the homologous recombination between the IS1 at min 0.4 and the IS1 transposed
      intermolecularly into the yiaK-S regulator gene. The participation of a rare IS1
      mediated inversion in the evolution of a stable phenotype is thus identified.

PMID- 9525948
TI  - gp180, a protein that binds duck hepatitis B virus particles, has
      metallocarboxypeptidase D-like enzymatic activity.
AB  - Duck gp180 was previously identified by its ability to bind to the preS envelope
      protein of duck hepatitis B virus particles (Kuroki, K. , Cheung, R., Marion, P.
      L., and Ganem, D. (1994) J. Virol. 68, 2091-2096). Cloning and sequencing of
      gp180 cDNA revealed that it is a polyprotein with three carboxypeptidase-like
      domains (Kuroki, K., Eng, F., Ishikawa, T., Turck, C., Harada, F., and Ganem, D.
      (1995) J. Biol. Chem. 270, 15022-15028). To evaluate enzymatic properties of this
      protein, a soluble 170-kDa form of the protein (gp170) lacking the C-terminal
      transmembrane domain and cytoplasmic tail was expressed in a baculovirus system.
      The purified 170-kDa protein cleaved 5-dimethylaminonaphthalene-1-sulfonyl
      (dansyl)-Phe-Ala-Arg with a pH optimum of 5.5-6.5. With this substrate at pH 5.5,
      the 170-kDa protein displayed a Km of 12 microM and a Kcat of 57 s-1. Dansyl-Pro
      Ala-Arg and dansyl-Phe-Phe-Arg were cleaved with Km values of 17 and 21 microM,
      and Kcat values of 57 and 17 s-1, respectively. Constructs containing only the
      first or second carboxypeptidase domains also showed enzymatic activity. The
      effects of inhibitors and ions on enzyme activity of gp170 were generally similar
      to the effects of these compounds on purified bovine carboxypeptidase D. To
      evaluate the regions within gp180 necessary for binding preS, a series of
      deletion mutants were expressed in the 293T human kidney cell line. Deletions of
      the first and second domains, leaving the third domain intact, eliminated
      carboxypeptidase activity but retained preS binding. Deletion of the third domain
      eliminated preS binding but not carboxypeptidase activity. These results indicate
      that the third domain is responsible for preS binding, and this binding does not
      require carboxypeptidase activity.

PMID- 9525949
TI  - p38 mitogen-activated protein kinase-dependent and -independent intracellular
      signal transduction pathways leading to apoptosis in human neutrophils.
AB  - Human neutrophils undergo apoptosis spontaneously when cultured in vitro;
      however, the signal transduction pathways involved remain largely unknown. In
      some cell types, c-Jun NH2-terminal kinase and p38 mitogen-activated protein
      kinase (MAPK) have been implicated in the pathways leading to stress-induced
      apoptosis. In this study, we begin to define two pathways leading to apoptosis in
      the neutrophil induced either by stress stimuli (UV, hyperosmolarity,
      sphingosine) or by anti-Fas antibody or overnight culture in vitro (spontaneous
      apoptosis). Apoptosis induced by stress stimuli activated p38 MAPK, and apoptosis
      was inhibited by the specific p38 MAPK inhibitor, 6-(4-Fluorophenyl)-2.3-dihydro
      5-(4-puridinyl)imidazo(2, 1-beta)thiazole dihydrochloride. Furthermore,
      differentiation of HL-60 cells toward the neutrophil phenotype resulted in a loss
      in c-Jun NH2-terminal kinase activation with concomitant acquisition of
      formylmethionylleucylphenylalanine-stimulatable and stress-inducible p38 MAPK
      activity as well as apoptosis blockade by the p38 MAPK inhibitor. In contrast,
      anti-Fas-induced or spontaneous apoptosis occurred independent of p38 MAPK
      activation and was not blocked by the inhibitor. Both pathways appear to utilize
      member(s) of the caspase family, since pretreatment with either Val-Ala-Asp
      fluoromethyl ketone or Asp-Glu-Val-Asp-fluoromethyl ketone inhibited apoptosis
      induced by each of the stimuli. We propose the presence of at least two pathways
      leading to apoptosis in human neutrophils, a stress-activated pathway that is
      dependent on p38 MAPK activation and an anti-FAS/spontaneous pathway that is p38
      MAPK-independent.

PMID- 9525950
TI  - Substitution of the degenerate smooth muscle (SM) alpha-actin CC(A/T-rich)6GG
      elements with c-fos serum response elements results in increased basal expression
      but relaxed SM cell specificity and reduced angiotensin II inducibility.
AB  - We have previously demonstrated that both CC(A/T-rich)6GG (CArG) elements A and B
      of the smooth muscle (SM) alpha-actin promoter are required for smooth muscle
      cell (SMC)-specific expression and angiotensin II (AII)-induced stimulation.
      Moreover, results provided evidence that AII responsiveness of SM alpha-actin was
      at least partially dependent on modulation of serum response factor (SRF) binding
      to the SM alpha-actin CArGs by the homeodomain containing protein, MHox. The goal
      of the present study was to investigate whether the degeneracy of the SM alpha
      actin CArGs (both contain a Gua or Cyt substitution in their A/T-rich center) and
      their reduced SRF binding activity as compared with c-fos serum response element
      (SRE) is important for conferring cell type-specific expression and AII
      responsiveness. Transient transfection assays using SM alpha-actin reporter gene
      constructs in which the endogenous SM alpha-actin CArGs were replaced by c-fos
      SREs demonstrated the following: 1) relaxation of cell-specific expression, 2) a
      50% reduction in AII responsiveness, and 3) reduced ability to be transactivated
      by MHox. In addition, we also showed that the position of the SM alpha-actin
      CArGs was important in that interchanging them abolished both basal and AII
      induced activities. Taken together, these results suggest that the reduced SRF
      binding activities of the SM alpha-actin CArGs and CArG positional context
      contribute to SMC-specific expression of SM alpha-actin as well as maximal AII
      responsiveness.

PMID- 9525951
TI  - Evidence for the presence of aquaporin-3 in human red blood cells.
AB  - A facilitated diffusion for glycerol is present in human erythrocytes. Glycerol
      transporters identified to date belong to the Major Intrinsic Protein (MIP)
      family of integral membrane proteins, and one of them, aquaporin-3 (AQP3), has
      been characterized in mammals. Using an antibody raised against a peptide
      corresponding to the rat AQP3 carboxyl terminus, we examined the presence of AQP3
      in normal and Colton-null (aquaporin-1 (AQP1)-deficient) human erythrocytes.
      Three immunoreactive bands were detected on immunoblots of both normal and Colton
      null red cells, very similar to the bands revealed in rat kidney, a material in
      which AQP3 has been extensively studied. By immunofluorescence, anti-AQP3
      antibodies stained the plasma membranes of both normal and Colton-null
      erythrocytes. Glycerol transport was measured on intact erythrocytes by stopped
      flow light scattering and on one-step pink ghosts by a rapid filtration
      technique. Glycerol permeability values, similar in both cell types, suggest that
      AQP1 does not represent the major path for glycerol movement across red blood
      cell membranes. Furthermore, pharmacological studies showed that Colton-null red
      cells remain sensitive to water and glycerol flux inhibitors, supporting the idea
      that another proteinaceous path, probably AQP3, mediates most of the glycerol
      movements across red cell membranes and represents part of the residual water
      transport activity found in AQP1-deficient red cells.

PMID- 9525952
TI  - Proinflammatory cytokines regulate expression of the lymphatic endothelial
      mitogen vascular endothelial growth factor-C.
AB  - Vascular endothelial growth factor (VEGF) is a prime regulator of normal and
      pathological angiogenesis. Three related endothelial cell growth factors, VEGF-B,
      VEGF-C, and VEGF-D were recently cloned. We have here studied the regulation of
      VEGF-C, a lymphatic endothelial growth factor, by angiogenic proinflammatory
      cytokines. Interleukin (IL)-1beta induced a concentration- and a time-dependent
      increase in VEGF-C, but not in VEGF-B, mRNA steady-state levels in human lung
      fibroblasts. The increase in VEGF-C mRNA levels was mainly due to increased
      transcription rather than elevated mRNA stability as detected by the nuclear run
      on method and by following mRNA decay in the presence of an inhibitor of
      transcription, respectively. In contrast, angiopoietin-1 mRNA, encoding the
      ligand for the endothelial-specific Tek/Tie-2 receptor, was down-regulated by IL
      1beta. Tumor necrosis factor-alpha and IL-1alpha also elevated VEGF-C mRNA steady
      state levels, whereas the IL-1 receptor antagonist and dexamethasone inhibited
      the effect of IL-1beta. Experiments with cycloheximide indicated that the effect
      of IL-1beta was independent of protein synthesis. Hypoxia, which is an important
      inducer of VEGF expression, had no effect on VEGF-B or VEGF-C mRNA levels. IL
      1beta and tumor necrosis factor-alpha also stimulated the production of VEGF-C
      protein by the fibroblasts. Cytokines and growth factors have previously been
      shown to down-regulate VEGF receptors in vascular endothelial cells. We found
      that the mRNA for the VEGF- and VEGF-C-binding VEGFR-2 (KDR/Flk-1) was stimulated
      by IL-1beta in human umbilical vein endothelial cells, whereas the mRNA levels of
      VEGFR-1 (Flt-1) and VEGFR-3 (Flt-4) were not altered. Our data suggest that in
      addition to VEGF, VEGF-C may also serve as an endothelial stimulus at sites of
      cytokine activation. In particular, these results raise the possibility that
      certain proinflammatory cytokines regulate the lymphatic vessels indirectly via
      VEGF-C.

PMID- 9525953
TI  - The protein translocation apparatus contributes to determining the topology of an
      integral membrane protein in Escherichia coli.
AB  - The assembly of integral membrane proteins is determined by features of these
      proteins and the protein translocation apparatus. We used alkaline phosphatase
      fusions to the membrane protein MalF to investigate the role of the protein
      translocation machinery in the arrangement of proteins in the cytoplasmic
      membrane of Escherichia coli. In particular, we studied the effects of prlA
      mutations on membrane protein topology. These mutations lie in the secY gene,
      which encodes a core component of the protein translocation apparatus. We find
      that the topology of some of the fusion proteins is changed and, in one case, is
      completely inverted in prlA mutants. We discuss the mechanism of prlA-mediated
      export and the role of the protein translocation apparatus in contributing to
      membrane protein topology.

PMID- 9525954
TI  - Increased camptothecin toxicity induced in mammalian cells expressing
      Saccharomyces cerevisiae DNA topoisomerase I.
AB  - The yeast Saccharomyces cerevisiae has been useful in establishing the phenotypic
      effects of specific mutations on the enzymatic activity and camptothecin
      sensitivity of yeast and human DNA topoisomerase I. To determine whether these
      phenotypes were faithfully reiterated in higher eukaryotic cells, wild-type and
      mutant yeast Top1 proteins were epitope-tagged at the amino terminus and
      transiently overexpressed in mammalian COS cells. Camptothecin preferentially
      induced apoptosis in cells expressing wild-type eScTop1p yet did not appreciably
      increase the cytotoxic response of cells expressing a catalytically inactive
      (eSctop1Y727F) or a catalytically active, camptothecin-resistant eSctop1vac
      mutant. Using an epitope-specific antibody, immobilized precipitates of eScTop1p
      were active in DNA relaxation assays, whereas immunoprecipitates of eScTop1Y727Fp
      were not. Thus, the enzyme retained catalytic activity while tethered to a
      support. Interestingly, the mutant eSctop1T722A, which mimics camptothecin
      induced cytotoxicity in yeast through stabilization of the covalent enzyme-DNA
      intermediate, induced apoptosis in COS cells in the absence of camptothecin. This
      correlated with increased DNA cleavage in immunoprecipitates of eScTop1T722Ap, in
      the absence of the drug. The observation that the phenotypic consequences of
      expressing wild-type and mutant yeast enzymes were reiterated in mammalian cells
      suggests that the mechanisms underlying cellular responses to DNA topoisomerase I
      mediated DNA damage are conserved between yeast and mammalian cells.

PMID- 9525955
TI  - In vivo regulation of scavenger receptor BI and the selective uptake of high
      density lipoprotein cholesteryl esters in rat liver parenchymal and Kupffer
      cells.
AB  - High density lipoprotein cholesteryl esters (HDL-CE) are selectively taken up by
      liver parenchymal cells without parallel apolipoprotein uptake. This selective
      uptake route forms an important step in the so-called reverse cholesterol
      transport. Scavenger receptor BI (SR-BI) is the only known HDL receptor which can
      mediate selective uptake of HDL-CE. In the present study we investigated its
      regulation in liver cells. The down-regulation of SR-BI expression in liver by
      17alpha-ethinyl estradiol (EE) treatment was found by immunoblotting to be the
      consequence of down-regulation of SR-BI in parenchymal cells, while SR-BI
      expression in Kupffer cells was up-regulated. The selective uptake of HDL-CE in
      vivo by parenchymal and Kupffer cells was measured by labeling of HDL with [3H]CE
      and analysis of the cellular uptake at 10 min after injection. After EE
      treatment, uptake of [3H]CE-labeled HDL by parenchymal cells decreased by 85%,
      while Kupffer cells showed a 4-fold increase in selective uptake of [3H]CE
      labeled HDL. In vitro studies with isolated parenchymal cells indicated that
      after EE treatment, the selective uptake of [3H]CE labeled HDL was 3-4-fold
      lower, indicating that the in vivo observations are also reflected in vitro. A 2
      week high-cholesterol diet leads to lowering of SR-BI expression in parenchymal
      cells, while the expression in Kupffer cells is increased. Like EE treatment, the
      selective uptake of [3H]CE-labeled HDL by the two hepatic cell types in vivo
      correlated with the changes in expression of SR-BI. Our results thus demonstrate
      that within the liver, the regulation of SR-BI expression by EE treatment or a
      high-cholesterol diet, correlates with changes in the selective uptake of HDL-CE,
      supporting a function of SR-BI to mediate the selective uptake of HDL-CE in the
      liver parenchymal cells. The contrasting regulatory effect on parenchymal cells
      and Kupffer cells might indicate a different function of SR-BI in the latter cell
      type.

PMID- 9525956
TI  - Identification of in vitro phosphorylation sites in the growth cone protein
      SCG10. Effect Of phosphorylation site mutants on microtubule-destabilizing
      activity.
AB  - SCG10 is a neuron-specific, membrane-associated protein that is highly
      concentrated in growth cones of developing neurons. Previous studies have
      suggested that it is a regulator of microtubule dynamics and that it may
      influence microtubule polymerization in growth cones. Here, we demonstrate that
      in vivo, SCG10 exists in both phosphorylated and unphosphorylated forms. By two
      dimensional gel electrophoresis, two phosphoisoforms were detected in neonatal
      rat brain. Using in vitro phosphorylated recombinant protein, four
      phosphorylation sites were identified in the SCG10 sequence. Ser-50 and Ser-97
      were the target sites for protein kinase A, Ser-62 and Ser-73 for mitogen
      activated protein kinase and Ser-73 for cyclin-dependent kinase. We also show
      that overexpression of SCG10 induces a disruption of the microtubule network in
      COS-7 cells. By expressing different phosphorylation site mutants, we have
      dissected the roles of the individual phosphorylation sites in regulating its
      microtubule-destabilizing activity. We show that nonphosphorylatable mutants have
      increased activity, whereas mutants in which phosphorylation is mimicked by
      serine-to-aspartate substitutions have decreased activity. These data suggest
      that the microtubule-destabilizing activity of SCG10 is regulated by
      phosphorylation, and that SCG10 may link signal transduction of growth or
      guidance cues involving serine/threonine protein kinases to alterations of
      microtubule dynamics in the growth cone.

PMID- 9525958
TI  - Identification and molecular cloning of a unique hyaluronan synthase from
      Pasteurella multocida.
AB  - Type A Pasteurella multocida, a prevalent animal pathogen, employs a hyaluronan
      [HA] polysaccharide capsule to avoid host defenses. We utilized transposon
      insertional mutagenesis to identify the P. multocida HA synthase, the enzyme that
      polymerizes HA. A DNA fragment from a wild-type genomic library could direct HA
      production in vivo in Escherichia coli, a bacterium that normally does not
      produce HA. Analysis of truncated plasmids derived from the original clone
      indicated that an open reading frame encoding a 972-residue protein was
      responsible for HA polymerization. This identification was confirmed by
      expression cloning in E. coli; we observed HA capsule formation in vivo and
      detected activity in membrane preparations in vitro. The polypeptide size was
      verified by photoaffinity labeling of the native P. multocida HA synthase with
      azido-UDP sugar analogs. Overall, the P. multocida sequence is not very similar
      to the other known HA synthases from streptococci, PBCV-1 virus, or vertebrates.
      Instead, a portion of the central region of the new enzyme is more homologous to
      the amino termini of other bacterial glycosyltransferases that produce different
      capsular polysaccharides or lipopolysaccharides. In summary, we have discovered a
      unique HA synthase that differs in sequence and predicted topology from the other
      known enzymes.

PMID- 9525957
TI  - Replication origin of the broad host range plasmid RK2. Positioning of various
      motifs is critical for initiation of replication.
AB  - The 393-base pair minimal origin, oriV, of plasmid RK2 contains three iterated
      motifs essential for initiation of replication: consensus sequences for binding
      the bacterial DnaA protein, DnaA boxes, which have recently been shown to bind
      the DnaA protein; 17-base pair direct repeats, iterons, which bind the plasmid
      encoded replication protein, TrfA; and A + T-rich repeated sequences, 13-mers,
      which serve as the initial site of helix destabilization. To investigate how the
      organization of the RK2 origin contributes to the mechanism of replication
      initiation, mutations were introduced into the minimal origin which altered the
      sequence and/or spacing of each particular region relative to the rest of the
      origin. These altered origins were analyzed for replication activity in vivo and
      in vitro, for localized strand opening and for DnaB helicase mediated unwinding.
      Mutations in the region between the iterons and the 13-mers which altered the
      helical phase or the intrinsic DNA curvature prevented strand opening of the
      origin and consequently abolished replication activity. Insertions of more or
      less than one helical turn between the DnaA boxes and the iterons also
      inactivated the replication origin. In these mutants, however, strand opening
      appeared normal but the levels of DnaB helicase activity were substantially
      reduced. These results demonstrate that correct helical phasing and intrinsic DNA
      curvature are critical for the formation of an open complex and that the DnaA
      boxes must be on the correct side of the helix to load DnaB helicase.

PMID- 9525959
TI  - Identification and partial characterization of factor Va heavy chain kinase from
      human platelets.
AB  - Factor Va, the essential cofactor for prothrombinase, is phosphorylated on the
      acidic COOH terminus of the heavy chain of the cofactor, at Ser692, by a platelet
      membrane-associated casein kinase II (CKII). Consistent with this observation,
      phosphorylation of the factor Va heavy chain by the platelet kinase was inhibited
      by heparin. The membrane-associated platelet CKII kinase was partially purified
      using heparin-agarose, phosphocellulose, and ion exchange chromatography. CKII
      antigen was monitored using a polyclonal antibody to the alpha-subunit, and
      kinase activity in the various fractions was confirmed using human factor Va as a
      substrate. Immunoblotting experiments using polyclonal antibodies raised against
      synthetic peptides mimicking a portion of the deduced amino acid sequence of the
      alpha-, alpha'-, and beta-subunits of human CKII demonstrated the coexistence of
      both alpha- and alpha'-subunits in platelets and suggested that the platelet CKII
      kinase may exist in part as an alpha alpha'beta2 complex. It is also possible
      that there are two distinct populations of CKII in platelets, one that is
      alphaalpha/betabeta and one that is alpha'alpha'/betabeta. In the presence of the
      purified platelet-derived CKII, human factor Va incorporates between 0.8 and 1.3
      mol of phosphate/mol of factor Va depending on the concentration of the beta
      subunit in the kinase preparation. A peptide mimicking the sequence 687-705 of
      the human factor V molecule incorporates radioactivity in the presence of
      purified CKII and inhibits factor Va heavy chain phosphorylation by the platelet
      CKII. In contrast, a peptide with an alanine instead of a serine at position 692
      neither incorporates phosphate nor inhibits factor Va phosphorylation by the
      platelet CKII. Human factor Va is inactivated by activated protein C following
      three cleavages of the heavy chain at Arg506, Arg306, and Arg679. Cleavage at
      Arg506 is necessary for efficient exposure of the inactivating cleavage site at
      Arg306. The phosphorylated cofactor has increased susceptibility to inactivation
      by activated protein C, since phosphorylated factor Va was found to be
      inactivated approximately 3-fold faster than its native counterpart. Acceleration
      of the inactivation process of the phosphorylated cofactor occurs because of
      acceleration of the rate of cleavage at Arg506. These data suggest a critical
      role for factor Va phosphorylation on the surface of platelets in regulating
      cofactor activity.

PMID- 9525960
TI  - Purification and characterization of 1-O-acylceramide synthase, a novel
      phospholipase A2 with transacylase activity.
AB  - A novel pathway for ceramide metabolism, 1-O-acylceramide formation, was
      previously reported (Abe, A., Shayman, J. A., and Radin, N. S. (1996) J. Biol.
      Chem. 271, 14383-14389). In this pathway a fatty acid in the sn-2 position of
      phosphatidylethanolamine or phosphatidylcholine is transferred to the 1-hydroxyl
      position of ceramide. An enzyme that catalyzes the esterification of N
      acetylsphingosine was purified from the postmitochondrial supernatant of calf
      brain through consecutive steps, including ammonium sulfate fractionation, DEAE
      Sephacel, phenyl-Sepharose, S-Sepharose, Sephadex G-75, concanavalin A-agarose,
      and heparin-Sepharose chromatography. The molecular mass of the enzyme was
      determined to be 40 kDa by gel filtration on Sephadex G-75. The enzyme bound to
      concanavalin A-agarose column was eluted with the buffer containing 500 mM alpha
      methyl-D-mannopyranoside. Further purification by heparin-Sepharose
      chromatography resulted in separation of two peaks of enzyme activity.
      Coincidence between the transacylase activity and a stained protein of a
      molecular mass of 40 kDa was observed, as determined by SDS-polyacrylamide gel
      electrophoresis and recovery after separation over an acidic native gel. The
      second peak of activity from the heparin-Sepharose chromatography represented a
      purification of 193,000-fold. These results are consistent with the enzyme being
      a glycoprotein of a molecular mass of about 40 kDa with a single polypeptide
      chain. The purified enzyme had a pH optimum at pH 4.5. The divalent cations Ca2+
      and Mg2+ enhanced but were not essential for the transacylase activity. Neither
      activation nor inactivation of the enzyme activity was observed in the presence
      of 2 mM ATP or 2 mM dithiothreitol. Preincubation of the enzyme with 1 mM N
      ethylmaleimide, 1 mM phenylmethylsulfonyl fluoride, or 3.1 microM bromoenol
      lactone, a potent inhibitor of cytosolic Ca2+-independent phospholipase A2, had
      no significant effect on the enzyme activity. The enzyme activity was completely
      abolished in the presence of greater than 773 microM Triton X-100. Partial
      inhibition of the enzyme activity was observed in the presence of 10-100
      microg/ml heparin. In the absence of N-acetylsphingosine, the enzyme acted as a
      phospholipase A2. These results strongly suggest that 1-O-acylceramide synthase
      is both a transacylase and a novel phospholipase A2.

PMID- 9525961
TI  - Modular folding and evidence for phosphorylation-induced stabilization of an
      hsp90-dependent kinase.
AB  - The de novo folding of the individual domains of the src family kinase p56(lck)
      was examined within the context of full-length p56(lck) molecules produced in
      rabbit reticulocyte lysate containing active chaperone machinery. The catalytic
      domain required geldanamycin-inhibitable heat shock protein 90 (hsp90) function
      to achieve its active protease-resistant conformation, but the src homology 2
      (SH2) domain acquired phosphopeptide-binding competence independently of hsp90
      function. The SH2 domain of hsp90-bound p56(lck) was folded and functional. In
      addition to the facilitation by hsp90 of kinase biogenesis, a conditional role in
      maintenance folding could be demonstrated; although wild type p56(lck) molecules
      with a negative-regulatory C-terminal tyrosine matured to a nearly hsp90
      independent state, p56(lck) molecules with a mutated C-terminal tyrosine
      continued to require hsp90-mediated maintenance. De novo folding could be
      distinguished from maintenance folding on the basis of proteolytic fingerprints
      and the effects of different temperatures on folding behavior. Results indicate
      that during p56(lck) biogenesis, the SH2 domain rapidly folds independently of
      hsp90 function, followed by the slower hsp90-dependent folding of the catalytic
      domain and suggest the final stabilization of p56(lck) structure by
      phosphorylation-mediated interdomain interactions.

PMID- 9525962
TI  - Heterodimeric DNA binding by the vitamin D receptor and retinoid X receptors is
      enhanced by 1,25-dihydroxyvitamin D3 and inhibited by 9-cis-retinoic acid.
      Evidence for allosteric receptor interactions.
AB  - Gel mobility shift analysis was utilized to investigate the molecular function of
      1alpha,25-dihydroxyvitamin D3 (1,25-(OH)2D3) and 9-cis-retinoic acid (9-cis-RA)
      ligands in the binding of the vitamin D receptor (VDR) and retinoid X receptor
      (RXR) to mouse osteopontin and rat osteocalcin vitamin D-response elements
      (VDREs). At physiological ionic strength and reduced concentrations of expressed
      proteins, efficient binding to either VDRE occurs as a VDR. RXR heterodimer, not
      as a VDR homodimer. 1,25-(OH)2D3 dramatically enhances heterodimer-VDRE
      interaction, whereas somewhat higher concentrations of 9-cis-RA inhibit this
      association, perhaps related to the role of this retinoid in facilitating RXR
      homodimer formation. Interestingly, if VDR is occupied by 1,25-(OH)2D3 prior to
      complexing with RXR, the resulting heterodimer is relatively resistant to
      dissociation and diversion to other pathways by 9-cis-RA. Therefore, a proposed
      molecular action of 1,25-(OH)2D3 is to generate an allosteric switch in VDR to a
      form that not only binds to the VDRE with high affinity and specificity as a
      heterodimer with RXR, but also interacts with the RXR partner to conformationally
      restrict the action of its cognate ligand.

PMID- 9525964
TI  - Binding of urokinase-type plasminogen activator to its receptor in MCF-7 cells
      activates extracellular signal-regulated kinase 1 and 2 which is required for
      increased cellular motility.
AB  - Binding of urokinase-type plasminogen activator (uPA) to its receptor, uPAR,
      regulates cellular adhesion, migration, and tumor cell invasion. Some of these
      activities may reflect the ability of uPAR to initiate signal transduction even
      though this receptor is linked to the plasma membrane only by a
      glycosylphosphatidylinositol anchor. In this study, we demonstrated that single
      chain uPA activates extracellular signal-regulated kinase 1 (ERK1) and ERK2 in
      MCF-7 breast cancer cells. Phosphorylation of ERK1 and ERK2 was increased 1 min
      after adding uPA and returned to baseline levels by 5 min. The amino-terminal
      fragment (ATF) of uPA, which binds to uPAR but lacks proteinase activity, also
      activated ERK1 and ERK2. Responses to uPA and ATF were eliminated when the cells
      were pretreated with PD098059, an inhibitor of mitogen-activated protein kinase
      kinase. uPA and ATF promoted the migration of MCF-7 cells across serum-coated
      Transwell membranes in vitro. Migration was increased 2.1 +/- 0.4-fold when uPA
      was added to the top chamber, 4. 8 +/- 0.8-fold when uPA was added to the bottom
      chamber, and 7.7 +/- 1.0-fold when uPA was added to both chambers. MCF-7 cells
      that were pulse-exposed to uPA for 30 min, and then washed to remove unbound
      ligand, demonstrated increased motility even though migration was allowed to
      occur for 24 h. PD098059 completely neutralized the effects of uPA on MCF-7
      cellular motility, irrespective of whether the uPA was present for the entire
      motility assay or administered by pulse-exposure. These results demonstrate a
      novel, receptor-dependent signaling activity which is required for uPA-stimulated
      breast cancer cell migration.

PMID- 9525963
TI  - MyoD is indispensable for muscle-specific alternative splicing in mouse
      mitochondrial ATP synthase gamma-subunit pre-mRNA.
AB  - Muscle-specific alternative RNA splicing is an essential step during myogenesis.
      In this paper, we report that a muscle-specific transcription factor, MyoD, plays
      a central role in the induction of muscle-specific alternative splicing during
      myogenesis. Recently, we reported that muscle and nonmuscle isoforms of the
      mitochondrial ATP synthase gamma-subunit (F1gamma) were generated by alternative
      splicing and that acidic stimulation promoted this muscle-specific alternative
      splicing (Endo, H., Matsuda, C., and Kagawa, Y. (1994) J. Biol. Chem. 269, 12488
      12493). In this report, mouse myoblasts are shown to express the muscle-specific
      isoform of F1gamma after induction with low-serum medium (differentiation medium)
      or acidic medium, although myotube formation was not detected after acidic
      induction. RNA blot analysis revealed that the expression levels of both MEF2 and
      myogenin were increased by low-serum induction, but not by acidic induction. High
      expression of MyoD mRNA was observed after both types of induction.
      Overexpression of exogenous MyoD in fibroblasts showed that MyoD was necessary
      for muscle-specific alternative splicing in both types of induction. Exogenous
      Id, a negative regulator of MyoD, blocked muscle-specific alternative splicing of
      F1gamma pre-mRNA by both types of induction. In addition, MyoD induced several
      muscle-specific alternative splicings, including structural protein pre-mRNAs
      such as beta-tropomyosin and neural-cell adhesion molecule and transcriptional
      protein pre-mRNAs such as MEF2A and MEF2D. Our analysis of the two induction
      systems shows a common MyoD-dependent mechanism of muscle-specific alternative
      splicing in several genes, independent of MEF2 and myogenin.

PMID- 9525965
TI  - Restoration of synthesis of sulfoglucuronylglycolipids in cerebellar granule
      neurons promotes dedifferentiation and neurite outgrowth.
AB  - Sulfoglucuronyl carbohydrate (SGC) linked to the terminal moiety of neolacto
      oligosaccharides is expressed in several glycoproteins of the immunoglobulin
      superfamily involved in neural cell-cell recognition as well as in two
      sulfoglucuronylglycolipids (SGGLs) of the nervous system. SGGLs and SGC
      containing glycoproteins are temporally and spatially regulated during
      development of the nervous system. In the cerebellum, the expression of SGC,
      particularly that of SGGLs, is biphasic. Several studies have suggested that the
      initial rise and decline in the levels of SGGLs and SGC-containing proteins
      correlated with the migration of granule neurons from the external granule cell
      layer to the internal granule cell layer and their subsequent maturation, whereas
      the later rise and continued expression of SGGLs in the adult was associated with
      their localization in the Purkinje neurons and their dendrites in the molecular
      layer. Here it is shown by immunocytochemical methods that the expression of SGC
      declined progressively in granule neurons isolated from cerebella of increasing
      age. The decline in the expression of SGC in granule neurons was also shown with
      time in culture. These results correlated with the previously shown declining
      activity of the regulatory enzyme lactosylceramide N
      acetylglucosaminyltransferase (GlcNAc-Tr) with age in vivo and in isolated
      granule neurons in culture. GlcNAc-Tr synthesizes a key precursor,
      lactotriosylceramide, involved in the biosynthesis of SGGL-1. The down-regulated
      synthesis of SGGLs in the mature granule neurons was shown by immunocytochemical
      and biochemical methods to be restored when a precursor,
      glucuronylneolactotetraosylceramide (GGL-1), which is beyond the GlcNAc-Tr step,
      was exogenously provided to these cells. The biological effect of such
      restoration of the synthesis of SGGLs in the mature granule neurons leads to cell
      aggregation and enhanced proliferation of neurites, amounting to
      dedifferentiation.

PMID- 9525966
TI  - Coagulation factor VII Gln100 --> Arg. Amino acid substitution at the epidermal
      growth factor 2-protease domain interface results in severely reduced tissue
      factor binding and procoagulant function.
AB  - We have used recombinant mammalian expression and purification of the factor VII
      (FVII) variant Gln100 --> Arg (Q100RFVII) to study FVII deficiency in subjects
      with this mutation. Q100RFVII was secreted poorly in comparison with wild-type
      FVII (WTFVII) in a stable mammalian expression system, and purified variant
      protein was found to have undetectable clotting activity. Following activation by
      immobilized factor Xa, Q100RFVIIa had amidolytic activity similar to WTFVIIa in
      the absence of soluble tissue factor (sTF); however, unlike WTFVIIa no typical
      increase in activity was seen after addition of sTF. In a factor X activation
      assay using relipidated transmembrane truncated tissue factor (residues 1-243),
      Q100RFVIIa showed less than 5% of the ability of WTFVIIa to activate factor X. We
      performed direct binding analysis of WT and Q100RFVII/FVIIa to immobilized sTF
      using surface plasmon resonance, and severely reduced binding of both non
      activated and activated Q100RFVII to sTF was seen, indicating a pronounced defect
      in tissue factor (TF) interaction with this variant. In the sTF-FVIIa crystal
      structure the candidate residue Gln100 is not in contact with TF but is at the
      epidermal growth factor 2-protease domain interface. We suggest that the mutation
      results in a global fold change severely reducing tissue factor interaction;
      mutation of FVII residues not directly involved in the interaction with TF may
      still result in variant FVII unable to take part in the initiation of
      coagulation.

PMID- 9525967
TI  - Transforming growth factor-beta1 stimulates protein kinase A in mesangial cells.
AB  - We recently demonstrated that transforming growth factor-beta (TGF-beta)
      stimulates phosphorylation of the type I inositol 1,4, 5-trisphosphate receptor
      (Sharma, K., Wang, L., Zhu, Y., Bokkala, S., and Joseph, S. (1997) J. Biol. Chem.
      272, 14617-14623), possibly via protein kinase A (PKA) activation in murine
      mesangial cells. In the present study, we evaluated whether TGF-beta stimulates
      PKA activation. Utilizing a specific PKA kinase assay, we found that TGF-beta
      increases PKA activity by 3-fold within 15 min of TGF-beta1 treatment, and the
      enhanced kinase activity was completely reversed by the inhibitory peptide for
      PKA (PKI; 1 microM). In mesangial cells transfected with a PKI expression vector,
      enhanced PKA activity could not be demonstrated with TGF-beta1 treatment. TGF
      beta1 was also found to stimulate translocation of the alpha-catalytic subunit of
      PKA to the nucleus by Western analysis of nuclear protein as well as by confocal
      microscopy. TGF-beta1-mediated phosphorylation of cAMP response element-binding
      protein was completely reversed by H-89 (3 microM), a specific inhibitor of PKA.
      Stimulation of fibronectin mRNA by TGF-beta1 was also attenuated in cells
      overexpressing PKI. We thus conclude that TGF-beta stimulates the PKA signaling
      pathway in mesangial cells and that PKA activation contributes to TGF-beta
      stimulation of cAMP response element-binding protein phosphorylation and
      fibronectin expression.

PMID- 9525968
TI  - The CYP2B2 phenobarbital response unit contains an accessory factor element and a
      putative glucocorticoid response element essential for conferring maximal
      phenobarbital responsiveness.
AB  - Hepatic cytochrome P450s play a critical role in the metabolism of hydrophobic
      xenobiotics. One of the major unsolved problems in xenobiotic metabolism is the
      molecular mechanism whereby phenobarbital induces hepatic enzymes, particularly
      CYP2B1 and CYP2B2 in rat liver. By using primary rat hepatocytes for transfection
      analyses, we previously identified in the CYP2B2 5'-flank a 163-base pair Sau3AI
      fragment that confers phenobarbital inducibility on a cat reporter gene and that
      has the properties of a transcriptional enhancer. Transfection experiments with
      sub-regions of the Sau3AI fragment now indicate that a central core together with
      an upstream or downstream accessory element within the fragment can confer
      phenobarbital responsiveness. One such accessory element, AF1, was identified and
      localized. DNase I footprinting analysis revealed the presence of a footprint
      overlapping this AF1 element. It also identified three other major protected
      regions, two of which are putative recognition sites for known transcription
      factors. Site-directed mutagenesis indicated that a putative glucocorticoid
      response element as well as a nuclear factor 1 site and an associated nuclear
      receptor hexamer half-site are essential for conferring maximal phenobarbital
      inducibility. Taken together, the results indicate that phenobarbital induction
      of CYP2B2 requires interactions among multiple regulatory proteins and cis-acting
      elements constituting a phenobarbital response unit.

PMID- 9525969
TI  - Differential interaction of coagulation factor VIII and factor V with protein
      chaperones calnexin and calreticulin.
AB  - Factor VIII (FVIII) and factor V (FV) are homologous coagulation cofactors
      sharing a similar domain organization (A1-A2-B-A3-C1-C2) and are both extensively
      glycosylated within their B-domains. In mammalian cell expression systems,
      compared with FV, the FVIII primary translation product is inefficiently
      transported out of the endoplasmic reticulum. Here we show that FVIII is degraded
      within the cell by a lactacystin-inhibitable pathway, implicating the cytosolic
      20 S proteasome machinery. Protein chaperones calnexin (CNX) and calreticulin
      (CRT) preferentially interact with glycoproteins containing monoglucosylated N
      linked oligosaccharides and are proposed to traffic proteins through degradative
      and/or secretory pathways. Utilizing co-immunoprecipitation assays, intracellular
      FVIII was detected in association with CNX maximally within 30 min to 1 h
      following synthesis, whereas FV could not be detected in association with CNX. In
      contrast, both FVIII and FV displayed interaction with CRT during transit through
      the secretory pathway. B-domain deleted FVIII significantly reduced the CNX and
      CRT interaction, indicating the B-domain may represent a primary CNX and CRT
      interaction site. In the presence of inhibitors of glucose trimming, the
      interactions of FVIII with CNX, and of FVIII and FV with CRT, were significantly
      reduced whereas the secretion of FVIII, and not FV, was inhibited. In addition,
      transfection in a glucosidase I-deficient Chinese hamster ovary cell line (Lec23)
      demonstrated that both degradation and secretion of FVIII were inhibited, with
      little effect on the secretion of FV. These results support that CNX and CRT
      binding, mediated at least in part by the B-domain of FVIII, is required for
      efficient FVIII degradation and secretion. In contrast, FV does not require CNX
      interaction for efficient secretion. The results suggest a unique requirement for
      carbohydrate processing and molecular chaperone interactions that may limit the
      productive secretion of FVIII.

PMID- 9525970
TI  - Diseases of abnormal protein glycosylation: an emerging area.

PMID- 9525971
TI  - Increased expression of the sodium/iodide symporter in papillary thyroid
      carcinomas.
AB  - Iodide is concentrated to a much lesser extent by papillary thyroid carcinoma as
      compared with the normal gland. The Na+/I- symporter (NIS) is primarily
      responsible for the uptake of iodide into thyroid cells. Our objective was to
      compare NIS mRNA and protein expression in papillary carcinomas with those in
      specimens with normal thyroid. Northern blot analysis revealed a 2.8-fold
      increase in the level of NIS mRNA in specimens with papillary carcinoma versus
      specimens with normal thyroid. Immunoblot analysis using anti-human NIS antibody
      that was produced with a glutathione S-transferase fusion protein containing NIS
      protein (amino acids 466-522) showed the NIS protein at 77 kD. The NIS protein
      level was elevated in 7 of 17 cases of papillary carcinoma but was not elevated
      in the normal thyroid. Immunohistochemical staining revealed abundant NIS in 8 of
      12 carcinomas, whereas NIS protein was barely detected in specimens with normal
      thyroid. Although considerable patient-to-patient variation was observed, our
      results indicate that NIS mRNA is elevated, and its protein tends to be more
      abundant, in a subset of papillary thyroid carcinomas than in normal thyroid
      tissue.

PMID- 9525972
TI  - Thrombomodulin modulates growth of tumor cells independent of its anticoagulant
      activity.
AB  - Thrombomodulin (TM), recognized as an essential vessel wall cofactor of the
      antithrombotic mechanism, is also expressed by a wide range of tumor cells. Tumor
      cell lines subcloned from four patients with malignant melanoma displayed a
      negative correlation between TM expression and cell proliferation in vitro and in
      vivo. Overexpression of wild-type TM decreased cell proliferation in vitro and
      tumor growth in vivo. TM mutants with altered protein C activation capacity lead
      to a similar effect. In contrast, transfection of melanoma cells with mutant TM
      constructs, in which a portion of the cytoplasmic or lectin domain was deleted,
      abrogated the antiproliferative effect associated with overexpression of wild
      type TM. Experiments performed with either peptide agonists/antagonists of the
      thrombin receptor, with hirudin, or with inhibitors of thrombin-TM interaction
      did not alter the growth inhibitory effect of TM overexpression. These data
      suggest that TM exerts an effect on cell proliferation independent of thrombin
      and the thrombin receptor, possibly related to the binding of novel ligands to
      determinants in the lectin domain which might trigger signal transduction
      pathways dependent on the cytoplasmic domain.

PMID- 9525973
TI  - Drug export activity of the human canalicular multispecific organic anion
      transporter in polarized kidney MDCK cells expressing cMOAT (MRP2) cDNA.
AB  - The canalicular (apical) membrane of the hepatocyte contains an ATP-dependent
      transport system for organic anions, known as the multispecific organic anion
      transporter (cMOAT). The deduced amino acid sequence of cMOAT is 49% identical to
      that of the human multidrug resistance- associated protein (MRP) MRP1, and cMOAT
      and MRP1 are members of the same sub-family of adenine nucleotide binding
      cassette transporters. In contrast to MRP1, cMOAT was predominantly found
      intracellularly in nonpolarized cells, suggesting that cMOAT requires a polarized
      cell for plasma membrane routing. Therefore, we expressed cMOAT cDNA in polarized
      kidney epithelial MDCK cell lines. When these cells are grown in a monolayer,
      cMOAT localizes to the apical plasma membrane. We demonstrate that cMOAT causes
      transport of the organic anions S-(2,4-dinitrophenyl)-glutathione, the
      glutathione conjugate of ethacrynic acid, and S-(PGA1)-glutathione, a substrate
      not shown to be transported by organic anion transporters previously. Transport
      is inhibited only inefficiently by compounds known to block MRP1. We also show
      that cMOAT causes transport of the anticancer drug vinblastine to the apical side
      of a cell monolayer. We conclude that cMOAT is a 5'-adenosine triphosphate
      binding cassette transporter that potentially might be involved in drug
      resistance in mammalian cells.

PMID- 9525974
TI  - Correction of renal tubular acidosis in carbonic anhydrase II-deficient mice with
      gene therapy.
AB  - Carbonic anhydrase II (CAII) deficiency in humans is associated with a syndrome
      of renal tubular acidosis, osteopetrosis, and cerebral calcification. A strain of
      mice of CAII deficiency due to a point mutation also manifests renal tubular
      acidosis. We report here that retrograde injection of cationic liposome complexed
      with a CAII chimeric gene, using a cytomegalovirus (CMV) promoter/enhancer as an
      expression cassette to drive human CAII cDNA, into the renal pelvis of CAII
      deficient mice results in expression of CAII in the kidney. The levels of both
      the CAII gene and its corresponding mRNA were highest by day 3 after treatment,
      diminishing thereafter, but remaining detectable by 1 mo. After gene therapy,
      CAII-deficient mice restored the ability to acidify urine after oral
      administration of ammonium chloride. The ability to acidify urine was maintained
      at 3 wk after gene therapy, and was eventually lost by 6 wk. Immunohistochemistry
      studies using anti-CAII antibodies showed that CAII was expressed in tubular
      cells of the outer medulla and corticomedullary junction. The gene therapy was
      not associated with nephrotoxicity as assessed by blood urea nitrogen levels and
      renal histology. To our knowledge, this is the first successful gene therapy of a
      genetic renal disease. Our results demonstrate the potential of gene therapy as a
      novel treatment for hereditary renal tubular defects.

PMID- 9525975
TI  - Stretch-mediated release of angiotensin II induces myocyte apoptosis by
      activating p53 that enhances the local renin-angiotensin system and decreases the
      Bcl-2-to-Bax protein ratio in the cell.
AB  - Physical forces activate apoptosis and gene expression, but the mechanism is
      unknown. For this purpose, adult myocytes were stretched in an equibiaxial
      stretch apparatus and the magnitude of cell death was examined 4 and 24 h later.
      The possibility of stretch-mediated activation of p53 and p53-dependent genes was
      evaluated at 30 min, 2, 4, 8, and 24 h. Myocyte apoptosis increased by 4.4- and
      7.6-fold at 4 and 24 h after stretch. p53 binding to the promoter of
      angiotensinogen, AT1 receptor, and Bax also increased. Expression of
      angiotensinogen, AT1 receptor, p53, and Bax increased and Bcl-2 decreased in
      stretched myocytes. The changes in AT1 receptor, p53, Bax, and Bcl-2 became more
      apparent with the duration of stretch. Angiotensin II concentration in the medium
      increased at 10 min, reaching maximal levels at 1 and 20 h. The AT1 blocker,
      losartan, abolished apoptosis in stretched myocytes. Myocyte volume was not
      influenced by stretch. In conclusion, stretch-mediated release of angiotensin II
      is coupled with apoptosis and the activation of p53 which may be responsible for
      the prolonged upregulation of the local renin-angiotensin system and the
      increased susceptibility of myocytes to undergo apoptosis.

PMID- 9525976
TI  - Inducible nitric oxide synthase expression in chronic viral hepatitis. Evidence
      for a virus-induced gene upregulation.
AB  - Increased nitric oxide (NO) production may contribute to the pathological changes
      featuring in some inflammatory diseases, but the role of NO in chronic viral
      hepatitis is still unknown. We compared the inducible NO synthase (NOS2)
      expression in the liver of patients with chronic viral hepatitis with that of
      both nonviral liver disease and histologically normal liver. NOS2 expression was
      assessed by immunohistochemical and in situ hybridization studies of liver biopsy
      sections. An intense hepatocellular NOS2 reactivity was detected in chronic viral
      hepatitis, whereas it was weakly or not observed in nonviral liver disease or
      normal liver, respectively. In addition, we determined whether the hepatitis B
      virus (HBV) might regulate the synthesis of this enzyme. NOS2 mRNA and protein
      levels as well as enzyme activity were assessed in cytokine-stimulated HBV
      transfected and untransfected hepatoma cells. Transfection with either HBV genome
      or HBV X gene resulted in induction of NOS2 mRNA expression, and the maximal
      induction of this transcript and NO production was observed in cytokine
      stimulated HBV-transfected cells. These results indicate that hepatotropic viral
      infections are able to upregulate the NOS2 gene expression in human hepatocytes,
      suggesting that NO may mediate important pathogenic events in the course of
      chronic viral hepatitis.

PMID- 9525977
TI  - Caloric restriction reverses hepatic insulin resistance in aging rats by
      decreasing visceral fat.
AB  - Hyperinsulinemia and increased visceral/abdominal fat (VF) are common features of
      human aging. To examine the relationships among VF, peripheral, and hepatic
      insulin sensitivity, we studied 4- and 18-mo-old male Sprague-Dawley rats (n =
      42) fed ad libitum (4 AL and 18 AL) or moderately calorie restricted (18 CR) up
      to 18 mo of age. Total fat mass (FM) and VF were decreased in 18 CR to
      approximately one-third of that of 18 AL (P < 0.001), while lean body mass (LBM)
      was unchanged. Most important, 18 CR had more FM (65+/-6 vs. 45+/-6 g) but less
      VF (7.8+/-0.6 vs. 12.3+/-3.3 g) compared with 4 AL (P < 0.01 for both). Thus, the
      effects of variable VF on HIS could be assessed, independent of FM and age.
      Marked hepatic insulin resistance ensued with aging (18 AL) and CR restored
      hepatic insulin sensitivity to the levels of young rats, while peripheral insulin
      sensitivity remained unchanged (by insulin clamp of 18 mU/kg/min). In fact, the
      rates of insulin infusion required to maintain basal hepatic glucose production
      in the presence of pancreatic clamp were 0.75+/-0.10, 1.41+/-0.13, and 0.51+/
      0.12 mU/kg . min, in 4 AL, 18 AL, and 18 CR, respectively (P < 0.01 between all
      groups), and in 18 CR rats infused with insulin at similar rates as in the 18 AL
      (1.4 mU/kg/min) hepatic glucose production was decreased by 32% (P < 0. 005).
      Furthermore, when 18 CR rats were fed AL for 14 d, VF rapidly and selectively
      increased and severe hepatic insulin resistance was induced. We propose that in
      this animal model the age-associated decrease in hepatic (rather than peripheral)
      insulin action is the major determinant of fasting hyperinsulinemia and that
      increased visceral adiposity plays the major role in inducing hepatic insulin
      resistance. Thus, interventions designed to prevent the accumulation of VF are
      likely to represent an effective mean to improve carbohydrate metabolism in
      aging.

PMID- 9525979
TI  - Requirement for binding of catalytically active factor VIIa in tissue factor
      dependent experimental metastasis.
AB  - Tissue factor (TF), the initiating cell surface receptor of the coagulation
      cascade, plays important roles in embryogenesis, angiogenesis, and tumor cell
      metastasis. It is controversial whether proteolytic function of TF complexed with
      its serine protease ligand VIIa is required for metastatic tumor dissemination.
      We show here in a model for TF-dependent experimental hematogenous metastasis,
      that TF supports metastasis by both proteolytic activity of the TF-VIIa complex
      and currently undefined functions of the cytoplasmic domain. We demonstrate that
      ligand binding of VIIa to TF is required for metastasis. Antimetastatic
      properties of covalently inactivated VIIa provide evidence that ligand binding is
      insufficient per se to support metastasis, emphasizing that proteolytic activity
      is necessary for the metastatic process. Ala or Asp mutations of cytoplasmic
      serine residues were introduced to preclude or mimic phosphorylation. In vivo
      analysis of these mutants suggests that local protease generation on the tumor
      cell surface does not serve simply to activate the cytoplasmic domain of TF by
      serine phosphorylation. Thus, extracellular functions of the catalytically active
      TF-VIIa complex cooperate with specific functions of the TF cytoplasmic domain to
      support the complex process of hematogenous tumor cell dissemination.

PMID- 9525978
TI  - Synovium as a source of increased amino-terminal parathyroid hormone-related
      protein expression in rheumatoid arthritis. A possible role for locally produced
      parathyroid hormone-related protein in the pathogenesis of rheumatoid arthritis.
AB  - Proinflammatory cytokines, including tumor necrosis factor (TNF) and interleukin
      1 (IL-1), mediate the joint destruction that characterizes rheumatoid arthritis
      (RA). Previous studies have shown that parathyroid hormone-related protein
      (PTHrP) is a member of the cascade of proinflammatory cytokines induced in
      parenchymal organs during lethal endotoxemia. To test the hypothesis that NH2
      terminal PTHrP, a potent bone resorbing agent, could also be a member of the
      synovial cascade of tissue-destructive cytokines whose expression is induced in
      RA, PTHrP expression was examined in synovium and synoviocytes obtained from
      patients with RA and osteoarthritis (OA). PTHrP production, as determined by
      measurement of immunoreactive PTHrP(1-86) in tissue explant supernatants, was
      increased 10-fold in RA versus OA synovial tissue. Synovial lining cells and
      fibroblast-like cells within the pannus expressed both PTHrP and the PTH/PTHrP
      receptor, findings that were confirmed by in vitro studies of cultured
      synoviocytes. TNF-alpha and IL-1beta stimulated PTHrP expression in synoviocytes,
      while dexamethasone and interferon-gamma, agents with some therapeutic efficacy
      in the treatment of RA, inhibited PTHrP release. Treatment of synoviocytes with
      PTHrP(1-34) stimulated IL-6 secretion. These results suggest that proinflammatory
      cytokine-stimulated production of NH2-terminal PTHrP by synovial tissue directly
      invading cartilage and bone in RA may mediate joint destruction through direct
      effects on cartilage or bone, or, indirectly, via the induction of mediators of
      bone resorption in the tumor-like synovium.

PMID- 9525980
TI  - HOXA10 is expressed in response to sex steroids at the time of implantation in
      the human endometrium.
AB  - Hox genes are well-known transcriptional regulators that play an essential role
      in directing embryonic development. Mice that are homozygous for a targeted
      disruption of the Hoxa10 gene exhibit uterine factor infertility. We have
      recently demonstrated that HOXA10 is expressed in the adult human uterus. To
      examine expression of HOXA10 during the menstrual cycle, Northern blot analysis
      and in situ hybridization were performed. Expression of HOXA10 dramatically
      increased during the midsecretory phase of the menstrual cycle, corresponding to
      the time of implantation and increase in circulating progesterone. Expression of
      HOXA10 in cultured endometrial cells was stimulated by estrogen or progesterone.
      Stimulation of HOXA10 by progesterone was concentration-dependent within the
      physiologic range, and the effect of estrogen was inhibited by cycloheximide.
      These results identify sex steroids as novel regulators of HOX gene expression.
      HOXA10 may have an important function in regulating endometrial development
      during the menstrual cycle and in establishing conditions necessary for
      implantation in the human.

PMID- 9525981
TI  - Regulation of Ca2+ signaling in transgenic mouse cardiac myocytes overexpressing
      calsequestrin.
AB  - To probe the physiological role of calsequestrin in excitation-contraction
      coupling, transgenic mice overexpressing cardiac calsequestrin were developed.
      Transgenic mice exhibited 10-fold higher levels of calsequestrin in myocardium
      and survived into adulthood, but had severe cardiac hypertrophy, with a twofold
      increase in heart mass and cell size. In whole cell-clamped transgenic myocytes,
      Ca2+ channel- gated Ca2+ release from the sarcoplasmic reticulum was strongly
      suppressed, the frequency of occurrence of spontaneous or Ca2+ current-triggered
      "Ca2+ sparks" was reduced, and the spark perimeter was less defined. In sharp
      contrast, caffeine-induced Ca2+ transients and the resultant Na+-Ca2+ exchanger
      currents were increased 10-fold in transgenic myocytes, directly implicating
      calsequestrin as the source of the contractile-dependent pool of Ca2+.
      Interestingly, the proteins involved in the Ca2+-release cascade (ryanodine
      receptor, junctin, and triadin) were downregulated, whereas Ca2+-uptake proteins
      (Ca2+-ATPase and phospholamban) were unchanged or slightly increased. The
      parallel increase in the pool of releasable Ca2+ with overexpression of
      calsequestrin and subsequent impairment of physiological Ca2+ release mechanism
      show for the first time that calsequestrin is both a storage and a regulatory
      protein in the cardiac muscle Ca2+-signaling cascade. Cardiac hypertrophy in
      these mice may provide a novel model to investigate the molecular determinants of
      heart failure.

PMID- 9525982
TI  - Enzyme replacement therapy for murine mucopolysaccharidosis type VII leads to
      improvements in behavior and auditory function.
AB  - Mucopolysaccharidosis type VII (MPS VII; Sly syndrome) is one of a group of
      lysosomal storage diseases that share many clinical features, including mental
      retardation and hearing loss. Lysosomal storage in neurons of the brain and the
      associated behavioral abnormalities characteristic of a murine model of MPS VII
      have not been shown to be corrected by either bone marrow transplantation or gene
      therapy. However, intravenous injections of recombinant beta-glucuronidase
      initiated at birth reduce the pathological evidence of disease in MPS VII mice.
      In this study we present evidence that enzyme replacement initiated at birth
      improved the behavioral performance and reduced hearing loss in MPS VII mice.
      Enzyme-treated MPS VII mice performed similarly to normal mice and significantly
      better than mock- treated MPS VII mice in every phase of the Morris Water Maze
      test. In addition, the auditory function of treated MPS VII mice was dramatically
      improved, and was indistinguishable from normal mice. These data indicate that
      some of the learning, memory, and hearing deficits can be prevented in MPS VII
      mice if enzyme replacement therapy is initiated early in life. These data also
      provide functional correlates to the biochemical and histopathological
      improvements observed after enzyme replacement therapy.

PMID- 9525983
TI  - Cationic liposomes target angiogenic endothelial cells in tumors and chronic
      inflammation in mice.
AB  - This study sought to determine whether angiogenic blood vessels in disease models
      preferentially bind and internalize cationic liposomes injected intravenously.
      Angiogenesis was examined in pancreatic islet cell tumors of RIP-Tag2 transgenic
      mice and chronic airway inflammation in Mycoplasma pulmonis-infected C3H/HeNCr
      mice. For comparison, physiological angiogenesis was examined in normal mouse
      ovaries. We found that endothelial cells in all models avidly bound and
      internalized fluorescently labeled cationic liposomes (1,2-dioleoyl-3
      trimethylammonium-propane [DOTAP]/cholesterol or dimethyldioctadecyl ammonium
      bromide [DDAB]/cholesterol) or liposome-DNA complexes. Confocal microscopic
      measurements showed that angiogenic endothelial cells averaged 15-33-fold more
      uptake than corresponding normal endothelial cells. Cationic liposome-DNA
      complexes were also avidly taken up, but anionic, neutral, or sterically
      stabilized neutral liposomes were not. Electron microscopic analysis showed that
      32% of gold-labeled liposomes associated with tumor endothelial cells were
      adherent to the luminal surface, 53% were internalized into endosomes and
      multivesicular bodies, and 15% were extravascular 20 min after injection. Our
      findings indicate that angiogenic endothelial cells in these models avidly bind
      and internalize cationic liposomes and liposome-DNA complexes but not other types
      of liposomes. This preferential uptake raises the possibility of using cationic
      liposomes to target diagnostic or therapeutic agents selectively to angiogenic
      blood vessels in tumors and sites of chronic inflammation.

PMID- 9525984
TI  - Carbohydrate-deficient glycoprotein syndrome type Ib. Phosphomannose isomerase
      deficiency and mannose therapy.
AB  - Phosphomannose isomerase (PMI) deficiency is the cause of a new type of
      carbohydrate-deficient glycoprotein syndrome (CDGS). The disorder is caused by
      mutations in the PMI1 gene. The clinical phenotype is characterized by protein
      losing enteropathy, while neurological manifestations prevailing in other types
      of CDGS are absent. Using standard diagnostic procedures, the disorder is
      indistinguishable from CDGS type Ia (phosphomannomutase deficiency). Daily oral
      mannose administration is a successful therapy for this new type of CDG syndrome
      classified as CDGS type Ib.

PMID- 9525985
TI  - Exendin(9-39)amide is an antagonist of glucagon-like peptide-1(7-36)amide in
      humans.
AB  - The gastrointestinal hormone, glucagon-like peptide-1(7-36)amide (GLP-1) is
      released after a meal. The potency of synthetic GLP-1 in stimulating insulin
      secretion and in inhibiting glucagon secretion indicates the putative
      physiological function of GLP-1. In vitro, the nonmammalian peptide, exendin(9
      39)amide [ex(9-39)NH2], is a specific and competitive antagonist of GLP-1. This
      in vivo study examined the efficacy of ex(9-39)NH2 as an antagonist of exogenous
      GLP-1 and the physiological role of endogenous GLP-1. Six healthy volunteers
      underwent 10 experiments in random order. In each experiment, a 30-min period of
      euglycemia was followed by an intravenous infusion of glucose for 150 min that
      established a stable hyperglycemia of 8 mmol/liter. There was a concomitant
      intravenous infusion of one of the following: (1) saline, (2) GLP-1 (for 60 min
      at 0.3 pmol . kg-1 . min-1 that established physiological postprandial plasma
      levels, and for another 60 min at 0.9 pmol . kg-1 . min-1 to induce
      supraphysiological plasma levels), (3-5) ex(9-39)NH2 at 30, 60, or 300 pmol . kg
      1 . min-1 + GLP-1, (6-8) ex(9-39)NH2 at 30, 60, or 300 pmol . kg-1 . min-1 +
      saline, (9 and 10) GIP (glucose-dependent insulinotropic peptide; for 60 min at
      0.8 pmol . kg-1 . min-1, with saline or ex(9-39)NH2 at 300 pmol . kg-1 . min-1).
      Each volunteer received each of these concomitant infusions on separate days.
      ex(9-39)NH2 dose-dependently reduced the insulinotropic action of GLP-1 with the
      inhibitory effect declining with increasing doses of GLP-1. ex(9-39)NH2 at 300
      pmol . kg-1 . min-1 blocked the insulinotropic effect of physiological doses of
      GLP-1 and completely antagonized the glucagonostatic effect at both doses of GLP
      1. Given alone, this load of ex(9-39)NH2 increased plasma glucagon levels during
      euglycemia and hyperglycemia. It had no effect on plasma levels of insulin during
      euglycemia but decreased plasma insulin during hyperglycemia. ex(9-39)NH2 did not
      alter GIP-stimulated insulin secretion. These data indicate that in humans, ex(9
      39)NH2 is a potent GLP-1 antagonist without any agonistic properties. The
      pancreatic A cell is under a tonic inhibitory control of GLP-1. At hyperglycemia,
      the B cell is under a tonic stimulatory control of GLP-1.

PMID- 9525986
TI  - Alpha2-adrenergic receptor-mediated release of lysophosphatidic acid by
      adipocytes. A paracrine signal for preadipocyte growth.
AB  - In the search for the existence of adrenergic regulation of the
      autocrine/paracrine function of the white adipose tissue, it was observed that
      conditioned media from isolated adipocytes or dialysates obtained by in situ
      microdialysis of human subcutaneous adipose tissue increased spreading and
      proliferation of 3T3F442A preadipocytes. These effects were amplified when an
      alpha2-adrenergic agonist was present during the obtention of conditioned media
      and microdialysates. This alpha2-adrenergic-dependent trophic activity was
      completely abolished by pretreatment of the conditioned media or microdialysates
      with the lysophospholipase, phospholipase B. Among the different
      lysophospholipids tested only lysophosphatidic acid (LPA) was able to induce
      spreading and proliferation of 3T3F442A preadipocytes. Moreover, previous chronic
      treatment of 3T3F442A preadipocytes with LPA which led to a specific
      desensitization of LPA responsiveness, abolished the alpha2-adrenergic-dependent
      trophic activities of the conditioned media and microdialysates. Finally, alpha2
      adrenergic stimulation led to a rapid, sustained, and pertussis toxin-dependent
      release of [32P]LPA from [32P]-labeled adipocytes. Based upon these results it
      was proposed that in vitro and in situ stimulation of adipocyte alpha2-adrenergic
      receptors provokes the extracellular release of LPA leading, in turn, to
      regulation of preadipocyte growth.

PMID- 9525987
TI  - Excess corticotropin releasing hormone-binding protein in the hypothalamic
      pituitary-adrenal axis in transgenic mice.
AB  - Corticotropin-releasing hormone (CRH) is the primary hypothalamic releasing
      factor that mediates the mammalian stress response. The CRH-binding protein (CRH
      BP) is secreted from corticotropes, the pituitary CRH target cells, suggesting
      that the CRH-BP may modulate hypothalamic-pituitary-adrenal (HPA) axis activity
      by preventing CRH receptor stimulation. Transgenic mice were generated that
      constitutively express elevated levels of CRH-BP in the anterior pituitary gland.
      RNA and protein analyses confirmed the elevation of pituitary CRH-BP. Basal
      plasma concentrations of corticosterone and adrenocorticotropin hormone (ACTH)
      are unchanged, and a normal pattern of increased corticosterone and ACTH was
      observed after restraint stress. However, CRH and vasopressin (AVP) mRNA levels
      in the transgenic mice are increased by 82 and 35%, respectively, to compensate
      for the excess CRH-BP, consistent with the idea that CRH-BP levels are important
      for homeostasis. The transgenic mice exhibit increased activity in standard
      behavioral tests, and an altered circadian pattern of food intake which may be
      due to transgene expression in the brain. Alterations in CRH and AVP in response
      to elevated pituitary CRH-BP clearly demonstrate that regulation of CRH-BP is
      important in the function of the HPA axis.

PMID- 9525988
TI  - Altered pattern of TCR/CD3-mediated protein-tyrosyl phosphorylation in T cells
      from patients with systemic lupus erythematosus. Deficient expression of the T
      cell receptor zeta chain.
AB  - Cellular immunity aberrations in patients with SLE are underscored by the
      abnormal early Ag receptor-mediated lymphocyte signal transduction pathway. To
      further characterize the T cell receptor (TCR)/CD3-initiated signaling defects,
      we studied 22 patients with SLE, 12 patients with other systemic rheumatic
      diseases, and 14 normal donors. The early (1 min) TCR/CD3-mediated tyrosine
      phosphorylation of cellular proteins with a molecular size between 36 and 64 kD
      was increased in 15 of 21 SLE patients, compared to normal or disease control
      subjects. The deficiency or absence of a band with a molecular size of
      approximately 16 kD in the immunoblots of SLE patients led us to investigate the
      expression of the TCRzeta chain. In immunoblots using anti-zeta antibodies we
      found that 10 of 22 lupus patients tested lacked the expression of TCRzeta, which
      was always present in control subjects (P < 0.001). Flow cytometric studies using
      permeabilized cells confirmed the deficiency or absence of the TCRzeta chain in
      lupus T cells. Using Northern blots we found that for eight patients tested, the
      TCRzeta mRNA was missing in three, decreased in three, and apparently normal in
      two patients (P < 0.003), but was always present in control subjects. Reverse
      transcriptase-PCR verified Northern blot results. We conclude that TCRzeta chain
      expression is either decreased or absent in the majority of patients with SLE,
      but not in patients with other systemic rheumatic diseases, regardless of disease
      activity, treatment status, or clinical manifestations. The previously described
      increases in TCR-initiated Ca2+ responses and the herein described increases in
      TCR-induced protein tyrosine phosphorylation and deficient TCRzeta expression may
      represent intrinsic defects modulating lupus T cell function.

PMID- 9525989
TI  - Plasma and lipids from stored packed red blood cells cause acute lung injury in
      an animal model.
AB  - Transfusion-related acute lung injury (TRALI) is a serious complication of
      hemotherapy. During blood storage, lipids are generated and released into the
      plasma. In this study, the role of these lipids in TRALI was investigated using
      an isolated, perfused rat lung model. Rats were pretreated with endotoxin (LPS)
      or saline in vivo and the lungs were isolated, ventilated, and perfused with
      saline, or (a) 5% (vol/ vol) fresh human plasma, (b) plasma from stored blood
      from the day of isolation (D.0) or from the day of outdate (D.42), (c) lipid
      extracts from D.42 plasma, or (d) purified lysophosphatidylcholines. Lungs from
      saline or LPS-pretreated rats perfused with fresh (D.0) plasma showed no
      pulmonary damage as compared with saline perfused controls. LPS pretreatment/D.42
      plasma perfusion caused acute lung injury (ALI) manifested by dramatic changes in
      both pulmonary artery pressure and edema. Incubation of LPS pre-tx rats with
      mibefradil, a Ca2+ channel blocker, or WEB 2170, a platelet-activating factor
      (PAF) receptor antagonist, inhibited ALI caused by D.42 plasma. Lung histology
      showed neutrophil sequestration without ALI with LPS pretreatment/saline or D.0
      plasma perfusion, but ALI with LPS pretreatment/D.42 plasma perfusion, and
      inhibition of D.42 plasma induced ALI with WEB 2170 or mibefradil. A significant
      increase in leukotriene E4 was present in LPS-pretreated/D.42 plasma-perfused
      lungs that was inhibited by WEB 2170. Lastly, significant pulmonary edema was
      produced when lipid extracts of D.42 plasma or lysophosphatidylcholines were
      perfused into LPS-pretreated lungs. Lipids caused ALI without vasoconstriction,
      except at the highest dose employed. In conclusion, both plasma and lipids from
      stored blood produced pulmonary damage in a model of acute lung injury. TRALI,
      like the adult respiratory distress syndrome, may be the result of two insults:
      one derived from stored blood and the other from the clinical condition of the
      patient.

PMID- 9525990
TI  - Altered wound healing in mice lacking a functional osteopontin gene (spp1).
AB  - Osteopontin (OPN) is an arginine-glycine-aspartate (RGD)- containing glycoprotein
      encoded by the gene secreted phosphoprotein 1 (spp1). spp1 is expressed during
      embryogenesis, wound healing, and tumorigenesis; however, its in vivo functions
      are not well understood. Therefore, OPN null mutant mice were generated by
      targeted mutagenesis in embryonic stem cells. In OPN mutant mice, embryogenesis
      occurred normally, and mice were fertile. Since OPN shares receptors with
      vitronectin (VN), we tested for compensation by creating mice lacking both OPN
      and VN. The double mutants were also viable, suggesting that other RGD-containing
      ligands replace the embryonic loss of both proteins. We tested the healing of OPN
      mutants after skin incisions, where spp1 was upregulated as early as 6 h after
      wounding. Although the tensile properties of the wounds were unchanged,
      ultrastructural analysis showed a significantly decreased level of debridement,
      greater disorganization of matrix, and an alteration of collagen fibrillogenesis
      leading to small diameter collagen fibrils in the OPN mutant mice. These data
      indicate a role for OPN in tissue remodeling in vivo, and suggest physiological
      functions during matrix reorganization after injury.

PMID- 9525991
TI  - Nicotinic receptor mediates nitric oxide synthase expression in the rat gastric
      myenteric plexus.
AB  - The mechanism that regulates the synthesis of nitric oxide synthase (NOS), a key
      enzyme responsible for NO production in the myenteric plexus, remains unknown. We
      investigated the roles of the vagal nerve and nicotinic synapses in the mediation
      of NOS synthesis in the gastric myenteric plexus in rats. Truncal vagotomy and
      administration of hexamethonium significantly reduced nonadrenergic,
      noncholinergic relaxation, the catalytic activity of NOS, the number of NOS
      immunoreactive cells, and the density of NOS-immunoreactive bands and NOS mRNA
      bands obtained from gastric tissue. These results suggest that NOS expression in
      the gastric myenteric plexus is controlled by the vagal nerve and nicotinic
      synapses. We also investigated if stimulation of the nicotinic receptor increases
      neuronal NOS (nNOS) expression in cultured gastric myenteric ganglia. Incubation
      of cultured gastric myenteric ganglia with the nicotinic receptor agonist, 1,1
      dimethyl-4-phenylpiperizinium (DMPP, 10(-10)-10(-7) M), for 24 h significantly
      increased the number of nNOS-immunoreactive cells and the density of
      immunoreactive nNOS bands and nNOS mRNA bands. nNOS mRNA expression stimulated by
      DMPP was antagonized by a protein kinase C antagonist, a phospholipase C
      inhibitor, and an intracellular Ca2+ chelator. We concluded that activation of
      the nicotinic receptor stimulates a Ca2+-dependent protein kinase C pathway,
      which in turn, upregulates nNOS mRNA expression and nNOS synthesis in the gastric
      myenteric plexus.

PMID- 9525992
TI  - A nonsense mutation in the carboxyl-terminal domain of type X collagen causes
      haploinsufficiency in schmid metaphyseal chondrodysplasia.
AB  - Type X collagen is a short-chain homotrimeric collagen expressed in the
      hypertrophic zone of calcifying cartilage. The clustering of mutations in the
      carboxyl-terminal NC1 domain in Schmid metaphyseal chondrodysplasia (SMCD)
      suggested a critical role for this type X collagen domain, but since no direct
      analysis of cartilage has been conducted in SMCD patients, the mechanisms of type
      X collagen dysfunction remain controversial. To resolve this problem, we obtained
      SMCD growth plate cartilage, determined the type X collagen mutation, and
      analyzed the expression of mutant and normal type X collagen mRNA and protein.
      The mutation was a single nucleotide substitution that changed the Tyr632 codon
      (TAC) to a stop codon (TAA). However, analysis of the expression of the normal
      and mutant allele transcripts in growth plate cartilage by reverse transcription
      PCR, restriction enzyme mapping, and a single nucleotide primer extension assay,
      demonstrated that only normal mRNA was present. The lack of mutant mRNA is most
      likely the result of nonsense-mediated mRNA decay, a common fate for transcripts
      carrying premature termination mutations. Furthermore, no mutant protein was
      detected by immunoblotting cartilage extracts. Our data indicates that a
      functionally null allele leading to type X collagen haploinsufficiency is the
      molecular basis of SMCD in this patient.

PMID- 9525993
TI  - Clearance of HSV-2 from recurrent genital lesions correlates with infiltration of
      HSV-specific cytotoxic T lymphocytes.
AB  - The mechanisms involved in host clearance of symptomatic mucocutaneous herpes
      simplex virus (HSV) infection are unclear. We studied the functional properties
      of bulk cultures of skin-infiltrating lymphocytes from normal skin and serial
      biopsies of recurrent genital HSV-2 lesions, and compared HSV-specific and NK
      responses with viral clearance. HSV-specific CD4+ or CD8+ T cells were rarely
      detected in lymphocytes cultured from normal skin. The total lymphocyte count and
      HSV-specific and NK-like effector cell activities were markedly higher in
      cultures derived from lesional skin. HSV-specific CD4+ proliferative responses
      and NK-like cytotoxic responses were present at all stages of herpetic lesions,
      including biopsies early in the disease course. In contrast, cytotoxic T
      lymphocyte activity was generally low among cells derived from early culture
      positive lesions, and increased during lesion evolution. Viral clearance from the
      lesion site was associated with a high level of local cytolytic activity towards
      HSV-infected cells. The phenotypes of cells with HSV-specific cytotoxic responses
      varied between patients, having CD4+ and CD8+ components. Immunotherapeutic
      approaches to HSV should be directed at improving in vivo cytolytic activity to
      HSV.

PMID- 9525994
TI  - Fibronectin and alpha5 integrin regulate keratinocyte cell cycling. A mechanism
      for increased fibronectin potentiation of T cell lymphokine-driven keratinocyte
      hyperproliferation in psoriasis.
AB  - In addition to being T lymphocyte-driven, psoriasis may be due in part to
      abnormal integrin expression. Normal-appearing (uninvolved) skin from psoriatic
      patients was examined to determine whether altered fibronectin or its receptor
      expression is detectable before development of psoriatic lesions. In contrast to
      skin from normal subjects, we detect by immunofluorescence the abnormal presence
      of plasma fibronectin in the basal cell layer of the epidermis of psoriatic
      uninvolved skin. Furthermore, increased fibronectin exposure superinduces the in
      vitro cell cycle induction and expansion of psoriatic nonlesional keratinocytes
      in response to a cocktail of T cell lymphokines. Fibronectin alone also appeared
      to increase cell cycle entry among uninvolved but not normal keratinocytes.
      Concordantly, the alpha5 integrin fibronectin receptor, but not alpha2 or alpha3,
      is overexpressed in the in vivo nonlesional psoriatic epidermis. The involvement
      of alpha5beta1 in the early outgrowth of clonogenic keratinocytes in the ex vivo
      culture was demonstrated by the ability of anti-alpha5 mAb to inhibit
      keratinocyte growth on fibronectin. Thus, the fibronectin receptor appears to be
      one of the components required for the development of the hyperresponsiveness of
      psoriatic keratinocytes to signals for proliferation provided by lymphokines
      produced by intralesional T lymphocytes in psoriasis.

PMID- 9525995
TI  - Bidirectional modulation of insulin action by amino acids.
AB  - Amino acids have been shown to stimulate protein synthesis, inhibit proteolysis,
      and decrease whole-body and forearm glucose disposal. Using cultured hepatoma and
      myotube cells, we demonstrate that amino acids act as novel signaling elements in
      insulin target tissues. Exposure of cells to high physiologic concentrations of
      amino acids activates intermediates important in the initiation of protein
      synthesis, including p70 S6 kinase and PHAS-I, in synergy with insulin. This
      stimulatory effect is largely due to branched chain amino acids, particularly
      leucine, and can be reproduced by its transamination product, ketoisocaproic
      acid. Concurrently, amino acids inhibit early steps in insulin action critical
      for glucose transport and inhibition of gluconeogenesis, including decreased
      insulin-stimulated tyrosine phosphorylation of IRS-1 and IRS-2, decreased binding
      of grb 2 and the p85 subunit of phosphatidylinositol 3-kinase to IRS-1 and IRS-2,
      and a marked inhibition of insulin-stimulated phosphatidylinositol 3-kinase.
      Taken together, these data support the hypothesis that amino acids act as
      specific positive signals for maintenance of protein stores, while inhibiting
      other actions of insulin at multiple levels. This bidirectional modulation of
      insulin action indicates crosstalk between hormonal and nutritional signals and
      demonstrates a novel mechanism by which nutritional factors contribute to insulin
      resistance.

PMID- 9525997
TI  - Ectopic cell cycle proteins predict the sites of neuronal cell death in
      Alzheimer's disease brain.
AB  - Alzheimer's disease (AD) is a major dementing illness characterized by regional
      concentrations of senile plaques, neurofibrillary tangles, and extensive neuronal
      cell death. Although cell and synaptic loss is most directly linked to the
      severity of symptoms, the mechanisms leading to the neuronal death remain
      unclear. Based on evidence linking neuronal death during development to
      unexpected reappearance of cell cycle events, we investigated the brains of 12
      neuropathologically verified cases of Alzheimer's disease and eight age-matched,
      disease-free controls for the presence of cell cycle proteins. Aberrant
      expression of cyclin D, cdk4, proliferating cell nuclear antigen, and cyclin B1
      were identified in the hippocampus, subiculum, locus coeruleus, and dorsal raphe
      nuclei, but not inferotemporal cortex or cerebellum of AD cases. With only one
      exception, control subjects showed no significant expression of cell cycle
      markers in any of the six regions. We propose that disregulation of various
      components of the cell cycle is a significant contributor to regionally specific
      neuronal death in AD.

PMID- 9525996
TI  - Tetrahydrobiopterin alters superoxide and nitric oxide release in prehypertensive
      rats.
AB  - Constitutive nitric oxide synthase (cNOS) with insufficient cofactor (6R)-5,6,7,8
      tetrahydrobiopterin (H4B) may generate damaging superoxide (O2-). This study was
      designed to determine whether cNOS-dependent generation of O2- occurs in
      spontaneously hypertensive rats (SHR) before the onset of hypertension. Aortas
      from 4-wk-old SHR and Wistar-Kyoto rats were used. cNOS was stimulated by calcium
      ionophore A23187. In situ measurements of nitric oxide and hydrogen peroxide by
      electrochemical sensors and O2- production by chemiluminescence method were
      performed. Isometric tension was continuously recorded. H4B by high performance
      liquid chromatography and [3H]citrulline assay were determined in homogenized
      tissue. The A23187-stimulated production of O2- and its superoxide dismutase
      product hydrogen peroxide were significantly higher, whereas nitric oxide release
      was reduced in SHR aortas, with opposite results in the presence of exogenous
      H4B. Furthermore, NG-monomethyl-L-arginine inhibited the generation of cNOS
      dependent O2- by approximately 70%. Natural H4B levels were similar in both
      strains; however, equivalent cNOS activity required additional H4B in SHR. The
      endothelium-dependent relaxations to A23187 were significantly inhibited by
      catalase, and enhanced by superoxide dismutase, only in SHR; however, these
      enzymes had no effect in the presence of H4B. Thus, dysfunctional cNOS may be a
      source of O2- in prehypertensive SHR and contribute to the development of
      hypertension and its vascular complications.

PMID- 9525998
TI  - Functional evidence that BDNF is an anterograde neuronal trophic factor in the
      CNS.
AB  - In this report, we have tested the hypothesis that brain-derived neurotrophic
      factor (BDNF) is an anterograde neurotrophic factor in the CNS and have focused
      on central noradrenergic neurons that synthesize BDNF. Double-label
      immunocytochemistry for BDNF and dopamine-beta-hydroxylase (DBH), a marker for
      noradrenergic neurons, demonstrated that BDNF is partially localized to
      noradrenergic nerve fibers and terminals in the adult rat brain. To test the
      functional importance of this anterograde BDNF, we analyzed transgenic mice
      carrying a DBH-BDNF minigene. Increased synthesis of BDNF in noradrenergic
      neurons of DBH-BDNF mice caused elevated TrkB tyrosine kinase activation
      throughout postnatal life in the neocortex, a noradrenergic target region. This
      afferently regulated increase in TrkB receptor activity led to long-lasting
      alterations in cortical morphology. To determine whether noradrenergic neuron
      expressed BDNF also anterogradely regulated neuronal survival, we examined a
      second noradrenergic target, neonatal facial motoneurons. One week after axotomy,
      72% of facial motoneurons were lost in control animals, whereas only 30-35% were
      lost in DBH-BDNF transgenic mice. Altogether, these results indicate that BDNF is
      anterogradely transported to fibers and terminals of noradrenergic neurons, that
      anterogradely secreted BDNF causes activation of TrkB in target regions, and that
      this secretion has functional consequences for target neuron survival and
      differentiation. This presynaptic secretion of BDNF may provide a cellular
      mechanism for modulating neural circuitry, in either the developing or mature
      nervous system.

PMID- 9525999
TI  - Mouse cerebellar granule cell differentiation: electrical activity regulates the
      GABAA receptor alpha 6 subunit gene.
AB  - GABAA receptor alpha6 subunit gene expression marks cerebellar granule cell
      maturation. To study this process, we used the Deltaalpha6lacZ mouse line, which
      has a lacZ reporter inserted into the alpha6 gene. At early stages of postnatal
      cerebellar development, alpha6-lacZ expression is mosaic; expression starts at
      postnatal day 5 in lobules 9 and 10, and alpha6-lacZ is switched on inside-out,
      appearing first in the deepest postmigratory granule cells. We looked for factors
      regulating this expression in cell culture. Membrane depolarization correlates
      inversely with alpha6-lacZ expression: granule cells grown in 25 mM [K+]o for 11
      15 d do not express the alpha6 gene, whereas cultures grown for the same period
      in 5 mM [K+]o do. This is influenced by a critical early period: culturing for
      >/=3 d in 25 mM [K+]o curtails the ability to induce the alpha6 gene on transfer
      to 5 mM [K+]o. If the cells start in 5 mM [K+]o, however, they still express the
      alpha6-lacZ gene in 25 mM [K+]o. In contrast to granule cells grown in 5 mM
      [K+]o, cells cultured in 25 mM [K+]o exhibit no action potentials, mEPSCs, or
      mIPSCs. In chronic 5 mM [K+]o, factors may therefore be released that induce
      alpha6. Blockade of ionotropic and metabotropic GABA and glutamate receptors or L
      , N-, and P/Q-type Ca2+ channels did not prevent alpha6-lacZ expression, but
      inhibition of action potentials with tetrodotoxin blocked expression in a
      subpopulation of cells.

PMID- 9526000
TI  - Protein kinase C disrupts cannabinoid actions by phosphorylation of the CB1
      cannabinoid receptor.
AB  - We have found that phosphorylation of a G-protein-coupled receptor by protein
      kinase C (PKC) disrupts modulation of ion channels by the receptor. In AtT-20
      cells transfected with rat cannabinoid receptor (CB1), the activation of an
      inwardly rectifying potassium current (Kir current) and depression of P/Q-type
      calcium channels by cannabinoids were prevented by stimulation of protein kinase
      C by 100 nM phorbol 12-myristate 13-acetate (PMA). In contrast, activation of Kir
      current by somatostatin was unaffected, and inhibition of calcium channels was
      only modestly attenuated. The possibility that PKC acted by phosphorylating CB1
      receptors was confirmed by demonstrating that PKC phosphorylated a single serine
      (S317) of a fusion protein incorporating the third intracellular loop of CB1.
      Mutating this serine to alanine did not affect the ability of CB1 to modulate
      currents, but it eliminated disruption by PMA, demonstrating that PKC can disrupt
      ion channel modulation by receptor phosphorylation.

PMID- 9526001
TI  - Episodic ataxia mutations in Kv1.1 alter potassium channel function by dominant
      negative effects or haploinsufficiency.
AB  - Subunits of the voltage-gated potassium channel Kv1.1 containing mutations
      responsible for episodic ataxia (EA), a human inherited neurological disease,
      were expressed in Xenopus oocytes. Five EA subunits formed functional homomeric
      channels with lower current amplitudes and altered gating properties compared
      with wild type. Two EA mutations located in the first cytoplasmic loop, R239S and
      F249I, yielded minimal or no detectable current, and Western blot analysis showed
      reduced protein levels. Coinjection of equal amounts of EA and wild-type mRNAs,
      mimicking the heterozygous condition, resulted in current amplitudes and gating
      properties that were intermediate between wild-type and EA homomeric channels,
      suggesting that heteromeric channels are formed with a mixed stoichiometry of EA
      and wild-type subunits. To examine the relative contribution of EA subunits in
      forming heteromeric EA and wild-type channels, each EA subunit was made
      insensitive to TEA, TEA-tagged, and coexpressed with wild-type subunits. TEA
      tagged R239S and F249I induced the smallest shift in TEA sensitivity compared
      with homomeric wild-type channels, whereas the other TEA-tagged EA subunits
      yielded TEA sensitivities similar to coexpression of wild-type and TEA-tagged
      wild-type subunits. Taken together, these results show that the different
      mutations in Kv1.1 affect channel function and indicate that both dominant
      negative effects and haplotype insufficiency may result in the symptoms of EA.

PMID- 9526002
TI  - N- and P/Q-type Ca2+ channels mediate transmitter release with a similar
      cooperativity at rat hippocampal autapses.
AB  - The relationship between extracellular Ca2+ concentration and EPSC amplitude was
      investigated at excitatory autapses on cultured hippocampal neurons. This
      relationship was steeply nonlinear, implicating the cooperative involvement of
      several Ca2+ ions in the release of each vesicle of transmitter. The
      cooperativity was estimated to be 3.1 using a power function fit and 3.3 using a
      Hill equation fit. However, simulations suggest that these values underestimate
      the true cooperativity. The role of different Ca2+ channel subtypes in shaping
      the Ca2+ dose-response relationship was studied using the selective Ca2+ channel
      blockers omega-agatoxin GIVA (omega-Aga), which blocks P/Q-type channels, and
      omega-conotoxin GVIA (omega-CTx), which blocks N-type channels. Both blockers
      broadened the dose-response relationship, and the Hill coefficient was reduced to
      2.5 by omega-Aga and to 2.6 by omega-CTx. This broadening is consistent with a
      nonuniform distribution of Ca2+ channel subtypes across presynaptic terminals.
      The similar Hill coefficients in omega-Aga or omega-CTx suggest that there was no
      difference in the degree of cooperativity for transmitter release mediated via N-
      or P/Q-type Ca2+ channels. A model of the role of calcium in transmitter release
      is developed. It is based on a modified Dodge-Rahamimoff equation that includes a
      nonlinear relationship between extracellular and intracellular Ca2+
      concentration, has a cooperativity of 4, and incorporates a nonuniform
      distribution of Ca2+ channel subtypes across presynaptic terminals. The model
      predictions are consistent with all of the results reported in this study.

PMID- 9526003
TI  - A reluctant gating mode of glycine receptor channels determines the time course
      of inhibitory miniature synaptic events in zebrafish hindbrain neurons.
AB  - Miniature IPSCs (mIPSCs) recorded in the Mauthner (M)-cell of zebrafish larvae
      have a broad amplitude distribution that is attributable only partly to the
      functional heterogeneity of postsynaptic glycine receptors (GlyRs). The role of
      the kinetic properties of GlyRs in amplitude fluctuation was investigated using
      fast-flow application techniques on outside-out patches. Short applications of a
      saturating glycine concentration evoked outside-out currents with a biphasic
      deactivation phase as observed for mIPSCs, and they were consistent with a rapid
      clearance of glycine from the synaptic cleft. Patch currents declined slowly
      during continuous applications of 3 mM glycine, but the biphasic deactivation
      phase of mIPSCs cannot reflect a desensitization process because paired-pulse
      desensitization was not observed. The maximum open probability (Po) of GlyRs was
      close to 0.9 with 3 mM glycine. Analyses of the onset of outside-out currents
      evoked by 0.1 mM glycine are consistent with the presence of two equivalent
      binding sites with a Kd of O.3-O.4 mM. Activation and deactivation properties of
      GlyRs were better described with a kinetic model, including two binding states, a
      doubly liganded open state, and a reluctant gating mode leading to another open
      state. The 20-80% rise time of mIPSCs was independent of their amplitude and is
      identical to that of outside-out currents evoked by the applications of a
      saturating concentration of glycine (>1 mM). These results support the hypothesis
      that GlyR kinetics determines the time course of synaptic events at M-cell
      inhibitory synapses and that large mIPSC amplitude fluctuations are mainly of
      postsynaptic origin.

PMID- 9526004
TI  - G alphas-induced neurodegeneration in Caenorhabditis elegans.
AB  - We describe a genetic model for neurodegeneration in the nematode Caenorhabditis
      elegans. Constitutive activation of the GTP-binding protein Galphas induces
      neurodegeneration. Neuron loss occurs in two phases whereby affected cells
      undergo a swelling response in young larvae and subsequently die sometime during
      larval development. Different neural cell types vary greatly in their
      susceptibility to Galphas-induced cytotoxicity, ranging from 0 to 88% of cells
      affected. Mutations that prevent programmed cell death do not prevent Galphas
      induced killing, suggesting that these deaths do not occur by apoptosis.
      Mutations in three genes protect against Galphas-induced cell deaths. The acy-1
      gene is absolutely required for neurodegeneration, and the predicted ACY-1
      protein is highly similar (40% identical) to mammalian adenylyl cyclases. Thus,
      Gs-induced neurodegeneration is mediated by the second messenger cAMP. Mutations
      in the unc-36 and eat-4 genes are partially neuroprotective, which indicates that
      endogenous signaling modulates the severity of the neurotoxic effects of Galphas.
      These experiments define an intracellular signaling cascade that triggers a
      necrotic form of neurodegeneration.

PMID- 9526006
TI  - Contributions of the optic tectum and the retina as sources of brain-derived
      neurotrophic factor for retinal ganglion cells in the chick embryo.
AB  - Retinal ganglion cells (RGC) are supported by brain-derived neurotrophic factor
      (BDNF), but it is not known if BDNF acts as a target-derived factor or as an
      afferent or autocrine trophic factor. Here we demonstrate that BDNF mRNA is
      expressed in the retinorecipient layer of the chick optic tectum as well as in
      the inner nuclear layer and ganglion cell layer of the retina. Amacrine cells
      rather than RGC were the main source of BDNF mRNA in the ganglion cell layer, as
      determined by in situ hybridization that was combined with retrograde labeling of
      RGC and destruction of RGC by optic stalk transection, followed by quantitative
      RT-PCR. Cells in the ganglion cell layer as well as the retinorecipient layers of
      the optic tectum were BDNF-immunolabeled. After injections into the tectum, radio
      iodinated BDNF was transported to the retina where autoradiographic label
      accumulated in the inner plexiform and ganglion cell layers. After intraocular
      injection, iodinated BDNF accumulated in these same retinal layers and correlated
      with the distribution of p75 neurotrophin receptor protein. The majority of cross
      linked receptor-bound BDNF in the retina immunoprecipitated with p75 antibodies.
      No difference in the intensity of BDNF immunolabel was observed in the
      experimental retina or tectum after optic stalk transection, indicating that most
      of the BDNF in the RGC was not derived from the optic tectum. These data indicate
      that a substantial fraction of the BDNF in the ganglion cell layer is derived
      from local sources, afferents within the retina, rather than from the optic
      tectum via retrograde transport.

PMID- 9526005
TI  - The expression of two splice variants of the Kv3.1 potassium channel gene is
      regulated by different signaling pathways.
AB  - The Kv3.1 potassium channel gene gives rise to two different channel proteins,
      Kv3.1a and Kv3.1b, by alternative splicing of nuclear RNA. During development the
      levels of Kv3.1b mRNA (but not Kv3.1a) substantially increase in rat cerebellum
      after postnatal day 8. The molecular mechanism underlying the differential
      regulation of the two transcripts is not known. Using in vitro slices of
      cerebellum, we have found that basic fibroblast growth factor (bFGF) upregulates
      both Kv3.1a and Kv3.1b at this developmental stage, but that depolarization by
      elevated potassium concentrations is without effect. Combined treatment with bFGF
      and depolarization, however, prevents the increase in Kv3.1a transcripts and
      selectively increases Kv3.1b mRNA levels. A protein kinase C (PKC) inhibitor
      blocks the increase in Kv3.1a mRNA levels induced by bFGF alone but does not
      affect the increase in Kv3.1b mRNA. Measurement of nuclear protein kinase C
      activity shows that bFGF activates this enzyme and that depolarization blocks
      this activation. In contrast to these findings at postnatal day 8, bFGF fails to
      alter Kv3.1 transcripts in slices from adult animals, and PKC activity is
      enhanced rather than suppressed by depolarization. Our results indicate that
      different signaling pathways regulate Kv3.1a and Kv3.1b expression and suggest
      that Kv3.1a mRNA levels may be modulated by neuronal activity.

PMID- 9526007
TI  - Protein kinase C activation increases release of secreted amyloid precursor
      protein without decreasing Abeta production in human primary neuron cultures.
AB  - Overexpression and altered metabolism of amyloid precursor protein (APP)
      resulting in increased 4 kDa amyloid beta peptide (Abeta) production are believed
      to play a major role in Alzheimer's disease (AD). Therefore, reducing Abeta
      production in the brain is a possible therapy for AD. Because AD pathology is
      fairly restricted to the CNS of humans, we have established human cerebral
      primary neuron cultures to investigate the metabolism of APP. In many cell lines
      and rodent primary neuron cultures, phorbol ester activation of protein kinase C
      (PKC) increases the release of the secreted large N-terminal fragment of amyloid
      precursor protein (sAPP) and decreases Abeta release (; ; ). In contrast, we find
      that PKC activation in human primary neurons increases the rate of sAPP release
      and the production of APP C-terminal fragments and 4 kDa Abeta. Our results
      indicate species- and cell type-specific regulation of APP metabolism. Therefore,
      our results curtail the use of PKC activators in controlling human brain Abeta
      levels.

PMID- 9526008
TI  - A Ca2+-independent receptor for alpha-latrotoxin, CIRL, mediates effects on
      secretion via multiple mechanisms.
AB  - alpha-Latrotoxin (alpha-Ltx), a component of black widow spider venom, stimulates
      secretion from nerve terminals and from PC12 cells. In this study we examine the
      effects of expression of a newly cloned Ca2+-independent receptor for alpha-Ltx
      (CIRL) on secretion from bovine chromaffin cells. We first characterized the
      effect of alpha-Ltx on secretion from untransfected cells. alpha-Ltx, by binding
      in a Ca2+-independent manner to an endogenous receptor, causes subsequent Ca2+
      dependent secretion from intact cells. The stimulation of secretion is correlated
      with Ca2+ influx caused by the toxin. In permeabilized cells in which the Ca2+
      concentration is regulated by buffer, alpha-Ltx also enhances Ca2+-dependent
      secretion, indicating a direct role of the endogenous receptor in the secretory
      pathway. Expression of CIRL increased the sensitivity of intact and permeabilized
      cells to the effects of alpha-Ltx, demonstrating that this protein is functional
      in coupling to secretion. Importantly, in the absence of alpha-Ltx, the
      expression of CIRL specifically inhibited the ATP-dependent component of
      secretion in permeabilized cells without affecting the ATP-independent secretion.
      This suggests that this receptor modulates the normal function of the regulated
      secretory pathway and that alpha-Ltx may act by reversing the inhibitory effects
      of the receptor.

PMID- 9526009
TI  - A neuronal Sec1 homolog regulates neurotransmitter release at the squid giant
      synapse.
AB  - Sec1-related proteins are essential for membrane fusion at distinct stages of the
      constitutive and regulated secretory pathways in eukaryotic cells. Studies of
      neuronal isoforms of the Sec1 protein family have yielded evidence for both
      positive and negative regulatory functions of these proteins in neurotransmitter
      release. Here, we have identified a squid neuronal homolog (s-Sec1) of Sec1
      proteins and examined its function in neurotransmitter release at the squid giant
      synapse. Microinjection of s-Sec1 into the presynaptic terminal of the giant
      synapse inhibited evoked neurotransmitter release, but this effect was prevented
      by coinjecting the cytoplasmic domain of squid syntaxin (s-syntaxin), one of the
      binding partners of s-Sec1. A 24 amino acid peptide fragment of s-Sec1, which
      inhibited the binding of s-Sec1 to s-syntaxin in vitro, completely blocked
      release, suggesting an essential function of the s-Sec1/s-syntaxin interaction in
      transmitter release. Electron microscopy showed that injection of s-Sec1 did not
      change the spatial distribution of synaptic vesicles at presynaptic release sites
      ("active zones"), whereas the inhibitory peptide increased the number of docked
      vesicles. These distinct morphological effects lead us to conclude that Sec1
      proteins function at different stages of synaptic vesicle exocytosis, and that an
      interaction of s-Sec1 with syntaxin-at a stage blocked by the peptide-is
      necessary for docked vesicles to fuse.

PMID- 9526010
TI  - Phosphatidylinositol 3-kinase and Akt protein kinase are necessary and sufficient
      for the survival of nerve growth factor-dependent sympathetic neurons.
AB  - Recent studies have suggested a role for phosphatidylinositol (PI) 3-kinase in
      cell survival, including the survival of neurons. We used rat sympathetic neurons
      maintained in vitro to characterize the potential survival signals mediated by PI
      3-kinase and to test whether the Akt protein kinase, a putative effector of PI 3
      kinase, functions during nerve growth factor (NGF)-mediated survival. Two PI 3
      kinase inhibitors, LY294002 and wortmannin, block NGF-mediated survival of
      sympathetic neurons. Cell death caused by LY294002 resembles death caused by NGF
      deprivation in that it is blocked by a caspase inhibitor or a cAMP analog and
      that it is accompanied by the induction of c-jun, c-fos, and cyclin D1 mRNAs.
      Treatment of neurons with NGF activates endogenous Akt protein kinase, and
      LY294002 or wortmannin blocks this activation. Expression of constitutively
      active Akt or PI 3-kinase in neurons efficiently prevents death after NGF
      withdrawal. Conversely, expression of dominant negative forms of PI 3-kinase or
      Akt induces apoptosis in the presence of NGF. These results demonstrate that PI 3
      kinase and Akt are both necessary and sufficient for the survival of NGF
      dependent sympathetic neurons.

PMID- 9526012
TI  - Evidence for a tetrameric structure of recombinant NMDA receptors.
AB  - The amino acids L-glutamate and glycine are essential agonists of the excitatory
      NMDA receptor, a subtype of the ionotropic glutamate receptor family. The native
      NMDA receptor is composed of two types of homologous membrane-spanning subunits,
      NR1 and NR2. Here, the numbers of glycine-binding NR1 and glutamate-binding NR2
      subunits in the NMDA receptor hetero-oligomer were determined by coexpressing the
      wild-type (wt) NR1 with the low-affinity mutant NR1(Q387K), and the wt NR2B with
      the low-affinity mutant NR2BE387A, subunits in Xenopus oocytes. In both cases,
      analysis of the resulting dose-response curves revealed three independent
      components of glycine and glutamate sensitivity. These correspond to the
      respective wild-type and mutant affinities and an additional intermediate hybrid
      affinity, indicating the existence of three discrete receptor populations.
      Binomial analysis of these data indicates the presence of two glycine and two
      glutamate binding subunits in the functional receptor. In addition, we analyzed
      the inhibitory effects of the negative dominant NR1(R505K) and NR2BR493K mutants
      on maximal inducible whole-cell currents of wt NR1/NR2B receptors. The inhibition
      profiles obtained on expression of increasing amounts of these mutant proteins
      again were fitted best by assuming an incorporation of two NR1 and two NR2
      subunits into the receptor hetero-oligomer. Our data are consistent with NMDA
      receptors being tetrameric proteins that are composed of four homologous
      subunits.

PMID- 9526011
TI  - The role of an alpha subtype M2-M3 His in regulating inhibition of GABAA receptor
      current by zinc and other divalent cations.
AB  - Sensitivity of GABAA receptors (GABARs) to inhibition by zinc and other divalent
      cations is influenced by the alpha subunit subtype composition of the receptor.
      For example, alpha6beta3gamma2L receptors are more sensitive to inhibition by
      zinc than alpha1beta3gamma2L receptors. We examined the role of a His residue
      located in the M2-M3 extracellular domain (rat alpha6 H273) in the enhanced zinc
      sensitivity conferred by the alpha6 subtype. The alpha1 subtype contains an Asn
      (N274) residue in the equivalent location. GABA-activated whole-cell currents
      were obtained from L929 fibroblasts after transient transfection with expression
      vectors containing GABAA receptor cDNAs. Mutation of alpha1 (alpha1(N274H)) or
      alpha6 (alpha6(H273N)) subtypes did not alter the GABA EC50 of alphabeta3gamma2L
      receptors. alpha1(N274H)beta3gamma2L receptor currents were as sensitive to zinc
      as alpha6beta3gamma2L receptor currents, although alpha6(H273N)beta3gamma2L
      receptor currents had the reduced zinc sensitivity of alpha1beta3gamma2L receptor
      currents. We also examined the activity of other inhibitory divalent cations with
      varying alpha subtype dependence: nickel, cadmium, and copper. alpha6beta3gamma2L
      receptor currents were more sensitive to nickel, equally sensitive to cadmium,
      and less sensitive to copper than alpha1beta3gamma2L receptor currents. Studies
      with alpha1 and alpha6 chimeric subunits indicated that the structural
      dependencies of the activity of some of these cations were different from zinc.
      Compared with alpha6beta3gamma2L receptor currents, alpha6(H273N)beta3gamma2L
      receptor currents had reduced sensitivity to cadmium and nickel, but the
      sensitivity to copper was unchanged. Compared with alpha1beta3gamma2L receptor
      currents, alpha1(N274H)beta3gamma2L receptor currents had increased sensitivity
      to nickel, but the sensitivity to cadmium and copper was unchanged. These
      findings indicate that H273 of the alpha6 subtype plays an important role in
      determining the sensitivity of recombinant GABARs to the divalent cations zinc,
      cadmium, and nickel, but not to copper. Our results also suggest that the
      extracellular N-terminal domain of the alpha1 subunit contributes to a regulatory
      site(s) for divalent cations, conferring high sensitivity to inhibition by copper
      and cadmium.

PMID- 9526014
TI  - Evidence that increased hippocampal expression of the cytokine interleukin-1 beta
      is a common trigger for age- and stress-induced impairments in long-term
      potentiation.
AB  - Several cytokines and their receptors are identified in brain; one of these is
      the proinflammatory cytokine interleukin-1beta that is synthesized and released
      from neurons and glia in response to stress or insult. Among the actions of
      interleukin-1beta is its ability to inhibit long-term potentiation in the
      hippocampus in vitro, an action that mimics one of the consequences of stress and
      age. It has been shown that the concentration of interleukin-1beta in brain
      tissue is increased in neurodegenerative conditions, and recent evidence from our
      laboratory has indicated an increase in the concentration of interleukin-1beta in
      the hippocampus of aged rats. These observations led us to consider that the
      underlying common cause of impaired long-term potentiation in aged and stressed
      rats might be increased endogenous interleukin-1beta concentration in
      hippocampus. The data presented here indicate that there was an inverse
      relationship between concentration of interleukin-1beta in the dentate gyrus and
      long-term potentiation in perforant path-->granule cell synapses in aged rats,
      stressed rats, and rats pretreated with interleukin-1beta. The evidence suggested
      that the cytokine induces formation of reactive oxygen species that triggers
      lipid peroxidation in vivo, as well as in vitro, and that these changes lead to
      depletion of membrane arachidonic acid that correlates with impaired long-term
      potentiation. We propose that three theories of aging, the glucocorticoid theory,
      the membrane theory, and the free radical theory, constitute three facets of age
      with one underlying trigger: an increase in the endogenous concentration of
      interleukin-1beta in hippocampus.

PMID- 9526013
TI  - Electrical properties of frog saccular hair cells: distortion by enzymatic
      dissociation.
AB  - Although it is widely accepted that the electrical resonance seen in many types
      of auditory and vestibular hair cells contributes to frequency selectivity in
      these sensory systems, unexplained discrepancies in the frequency (f) and
      sharpness (Q) of tuning have raised serious questions. For example, enzymatically
      dissociated hair cells from bullfrog (Rana catesbeiana) sacculus resonate at
      frequencies well above the range of auditory and seismic stimuli to which the
      sacculus is most responsive. Such disparities, in addition to others, have led to
      the proposal that electrical resonance alone cannot account for frequency tuning.
      Using grassfrog (Rana pipiens) saccular hair cells, we show that the reported
      discrepancies in f and Q in this organ can be explained by the deleterious
      effects of enzyme (papain) exposure during cell dissociation. In patch-clamp
      studies of hair cells in a semi-intact epithelial preparation, we observed a
      variety of voltage behaviors with frequencies of 35-75 Hz. This range is well
      below the range of resonant frequencies observed in enzymatically dissociated
      hair cells and more in tune with the frequency range of natural stimuli to which
      the sacculus is maximally responsive. The sharpness of tuning also agreed with
      previous studies using natural stimuli. In contrast to results from enzymatically
      dissociated hair cells, both a calcium-activated K+ (KCa) current and a voltage
      dependent K+ (KV) current contributed to the oscillatory responses of hair cells
      in the semi-intact preparation. The properties of the KCa and the Ca2+ current
      were altered by enzymatic dissociation. KV and a small-conductance calcium
      activated K+ current were apparently eliminated.

PMID- 9526015
TI  - Regulation of presynaptic NMDA responses by external and intracellular pH changes
      at developing neuromuscular synapses.
AB  - NMDA receptors play important roles in synaptic plasticity and neuronal
      development. The functions of NMDA receptors are modulated by many endogenous
      substances, such as external pH (pHe), as well as second messenger systems. In
      the present study, the nerve-muscle cocultures of Xenopus embryos were used to
      investigate the effects of both external and intracellular pH (pHi) changes on
      the functional responses of presynaptic NMDA receptors. Spontaneous synaptic
      currents (SSCs) were recorded from innervated myocyte using whole-cell
      recordings. Local perfusion of NMDA at synaptic regions increased the SSC
      frequency via the activation of presynaptic NMDA receptors. A decrease in pHe
      from 7.6 to 6.6 reduced NMDA responses to 23% of the control, and an increase in
      pHe from 7.6 to 8.6 potentiated the NMDA responses in increasing SSC frequency.
      The effect of NMDA on intracellular Ca2+ concentration ([Ca2+]i) was also
      affected by pHe changes: external acidification inhibited and alkalinization
      potentiated [Ca2+]i increases induced by NMDA. Intracellular pH changes of single
      soma were measured by ratio fluorometric method using 2,7-bis (carboxyethyl)-5, 6
      carboxyfluorescein (BCECF). Cytosolic acidification was used in which NaCl in
      Ringer's solution was replaced with weak organic acids. Acetate and propionate
      but not methylsulfate substitution caused intracellular acidification and
      potentiated NMDA responses in increasing SSC frequency, intracellular free Ca2+
      concentration, and NMDA-induced currents. On the other hand, cytosolic
      alkalinization with NH4Cl did not significantly affect these NMDA responses.
      These results suggest that the functions of NMDA receptors are modulated by both
      pHe and pHi changes, which may occur in some physiological or pathological
      conditions.

PMID- 9526016
TI  - Two receptor tyrosine phosphatases of the LAR family are expressed in the
      developing leech by specific central neurons as well as select peripheral
      neurons, muscles, and other cells.
AB  - Receptor protein tyrosine phosphatases (rPTPs) are thought to play a crucial role
      in neuronal development, particularly in pathfinding by growing processes. We
      have cloned and sequenced two Hirudo medicinalis rPTPs that are homologous to the
      Drosophila and vertebrate rPTPs of the Leukocyte common antigen-related (LAR)
      subfamily. These Hirudo rPTPs, HmLAR1 and HmLAR2, are products of different,
      homologous genes, both containing two tandem intracellular phosphatase domains
      and ectodomains with three tandem Ig domains and different numbers of tandem
      fibronectin type III (FIII) domains. They are expressed in distinct patterns
      during embryogenesis. HmLAR1 mRNA is expressed by a subset of central and
      peripheral neurons and by several peripheral muscular structures, whereas HmLAR2
      mRNA is expressed by a different subset of central neurons and by the peripheral,
      neuron-like Comb cells. HmLAR1 and HmLAR2 proteins are located on the neurites of
      central neurons. In addition, HmLAR2 is expressed on the cell body, processes,
      and growth cones of the Comb cells. Because of their CAM-like ectodomains and
      homology to proteins known to be involved in pathfinding and because they are
      expressed by different subsets of neurons, we hypothesize that HmLAR1 and HmLAR2
      participate in navigational decisions that distinguish the sets of neurons that
      express them. Furthermore, we hypothesize that HmLAR2 is also involved in setting
      up the highly regular array of parallel processes established by the Comb cells.
      Lastly, we propose that the HmLAR1 ectodomain on peripheral muscle cells plays a
      role in target recognition via interactions with neuronal receptors, which might
      include HmLAR1 or HmLAR2.

PMID- 9526017
TI  - Development of a sexually dimorphic projection from the bed nuclei of the stria
      terminalis to the anteroventral periventricular nucleus in the rat.
AB  - The principal nucleus of the bed nuclei of the stria terminalis (BSTp) is larger
      in male rats and conveys olfactory information relevant for reproduction to the
      hypothalamus. In males, the BSTp provides a massive projection to the
      anteroventral periventricular nucleus of the preoptic region (AVPV), which in
      contrast to most sexually dimorphic nuclei contains more neurons in female rats.
      Injections of the anterograde tracer Phaseolus vulgaris leucoagglutinin into the
      BSTp of adult female rats failed to demonstrate the strong projection to the AVPV
      observed previously in males. The ontogeny of this robust sex difference was
      examined by using the axonal marker DiI. The projection from the BSTp to the AVPV
      is established between postnatal day 9 (P9) and P10 in male rats and seems to be
      maintained during the juvenile period. Although labeled fibers extended from the
      BSTp toward the preoptic region in both male and female neonates, a similar
      connection with the AVPV was not apparent in female rats at any of the ages
      studied, and the density of labeled axons in the AVPV of P10 males was 20-fold
      greater than that of P10 females. A projection from the BSTp to the medial
      preoptic nucleus was also weaker in females but was much more substantial than
      that to the AVPV. These findings suggest that a sex- and region-specific activity
      influences the development of the projection from the BSTp to the AVPV, producing
      a sexually dimorphic architecture in pathways that convey olfactory information
      to the hypothalamus.

PMID- 9526018
TI  - Phase shifting of circadian rhythms and depression of neuronal activity in the
      rat suprachiasmatic nucleus by neuropeptide Y: mediation by different receptor
      subtypes.
AB  - Neuropeptide Y (NPY) has been implicated in the phase shifting of circadian
      rhythms in the hypothalamic suprachiasmatic nucleus (SCN). Using long-term,
      multiple-neuron recordings, we examined the direct effects and phase-shifting
      properties of NPY application in rat SCN slices in vitro (n = 453). Application
      of NPY and peptide YY to SCN slices at circadian time (CT) 7.5-8.5 produced
      concentration-dependent, reversible inhibition of cell firing and a subsequent
      significant phase advance. Several lines of evidence indicated that these two
      effects of NPY were mediated by different receptors. NPY-induced inhibition and
      phase shifting had different concentration-response relationships and very
      different phase-response relationships. NPY-induced phase advances, but not
      inhibition, were blocked by the GABAA antagonist bicuculline, suggesting that NPY
      mediated modulation of GABA may be an underlying mechanism whereby NPY phase
      shifts the circadian clock. Application of the Y2 receptor agonists NPY 13-36 and
      (Cys2,8-aminooctanoic acid5,24,D-Cys27)-NPY advanced the peak of the circadian
      rhythm but did not inhibit cell firing. The Y1 and Y5 agonist [Leu31,Pro34]-NPY
      evoked a substantial inhibition of discharge but did not generate a phase shift.
      NPY-induced inhibition was not blocked by the specific Y1 antagonist BIBP-3226;
      the antagonist also had no effect on the timing of the peak of the circadian
      rhythm. Application of the Y5 agonist [D-Trp32]-NPY produced only direct neuronal
      inhibition. These are the first data to indicate that at least two functional
      populations of NPY receptors exist in the SCN, distinguishable on the basis of
      pharmacology, each mediating a different physiological response to NPY
      application.

PMID- 9526019
TI  - Localization of genes mediating acute and sensitized locomotor responses to
      cocaine in BXD/Ty recombinant inbred mice.
AB  - Sensitization to the psychostimulant effects of cocaine has received widespread
      attention because concomitant changes occur in neurochemical pathways that are
      part of the brain reward pathway. The current study was undertaken with the
      purpose of mapping genes determining sensitivity to the acute stimulant and
      sensitizing effects of cocaine. Sensitivity and sensitization to cocaine (5, 10,
      and 40 mg/kg) were measured in 25 BXD/Ty recombinant inbred (BXD RI) strains and
      the progenitor C57BL/6J (B6) and DBA/2J (D2) strains. Quantitative trait locus
      (QTL) mapping provisionally localized cocaine sensitivity genes to regions on all
      chromosomes except 6, 11, 17, and X; sensitization QTLs were localized to
      chromosomes 1-10, 13, 15, 18, 19, and X. Provisional QTLs for locomotion after
      saline injection in a novel setting were mapped to chromosomes 1, 3-6, 9, 12, 13,
      18, and 19 and in a familiar setting to chromosomes 4-7, 9, 13, and 19. There
      were both common and unique QTL regions across the phenotypes. Evidence for a
      genetic association between magnitude of acute cocaine response and sensitization
      was obtained for only the 10 mg/kg dose. Some common QTL regions for cocaine,
      ethanol, and methamphetamine responses suggest the possibility that these drugs
      induce stimulant effects or sensitization through some common mechanisms.
      However, independent mechanisms were also indicated. Many candidate genes reside
      near the provisional QTLs mapped for cocaine responses, including genes coding a
      variety of neurotransmitter and hormone receptors. These data, once confirmed,
      should prove useful for directing investigations of acute and chronic cocaine
      effects down already suspected and novel avenues.

PMID- 9526020
TI  - Adrenergic alpha2C-receptors modulate the acoustic startle reflex, prepulse
      inhibition, and aggression in mice.
AB  - Studies on animal models of stress, anxiety, aggression, and sensorimotor gating
      have linked specific monoamine neurotransmitter abnormalities to the cognitive
      and behavioral disturbances associated with many affective neuropsychiatric
      disorders. Although alpha2-adrenoceptors (alpha2-ARs) have been suggested to have
      a modulatory role in these disorders, the specific roles of each alpha2-AR
      subtype (alpha2A, alpha2B, and alpha2C) are largely unknown. The restricted
      availability of relevant animal models and the lack of subtype-selective alpha2
      AR drugs have precluded detailed studies in this area. Therefore, transgenic mice
      were used to study the possible role of the alpha2C-AR subtype in two well
      established behavioral paradigms: prepulse inhibition (PPI) of the startle reflex
      and isolation-induced aggression. The alpha2C-AR-altered mice appear grossly
      normal, but subtle changes have been observed in their brain dopamine (DA) and
      serotonin (5-HT) metabolism. In this study, the mice with targeted inactivation
      of the gene encoding alpha2C-ARs (alpha2C-KO) had enhanced startle responses,
      diminished PPI, and shortened attack latency in the isolation-aggression test,
      whereas tissue-specific overexpression of alpha2C-ARs (alpha2C-OE) was associated
      with opposite effects. Correlation analyses suggested that both the magnitude of
      the startle response and its relative PPI (PPI%) were modulated by the mutations.
      In addition, the differences in PPI, observed between drug-naive alpha2C-OE mice
      and their wild-type controls, were abolished by treatment with a subtype
      nonselective alpha2-agonist and antagonist. Thus, drugs acting via alpha2C-ARs
      might have therapeutic value in disorders associated with enhanced startle
      responses and sensorimotor gating deficits, such as schizophrenia, attention
      deficit disorder, post-traumatic stress disorder, and drug withdrawal.

PMID- 9526021
TI  - Vagotomy-induced enhancement of mechanical hyperalgesia in the rat is
      sympathoadrenal-mediated.
AB  - We have recently shown that subdiaphragmatic vagotomy enhances bradykinin-induced
      hyperalgesic behavior and decreases baseline paw withdrawal threshold to
      mechanical stimulation of the hindpaw skin in rats by a peripheral mechanism. To
      elucidate the underlying mechanism, we studied whether lesions of efferent
      neuroendocrine pathways could prevent or reverse the potentiating effect of
      vagotomy. In groups of sham-vagotomized or vagotomized rats, we surgically
      removed or denervated the adrenal medulla. Bradykinin was injected intradermally
      into the skin of the dorsal surface of the rat hindpaw. Threshold of paw
      withdrawal to mechanical stimulation of the skin was measured. Vagotomy induced a
      decrease in mechanical baseline paw withdrawal threshold and enhancement of
      bradykinin-induced mechanical hyperalgesic behavior, both of which were
      maintained over the 5 week testing period. Adrenal enucleation or denervation of
      the adrenal gland by suprarenal ganglionectomy prevented vagotomy-induced
      decrease in baseline paw withdrawal threshold and enhancement of bradykinin
      induced hyperalgesia. In animals that had a demonstrated decrease in baseline paw
      withdrawal threshold and enhancement of bradykinin-induced hyperalgesia 2 weeks
      after vagotomy, additional denervation of the adrenal medulla significantly
      reversed these effects over a 3 week period. These results imply that both the
      decrease in baseline paw withdrawal threshold and enhancement of bradykinin
      induced hyperalgesic behavior after vagotomy are dependent on a hormonal signal
      released from the adrenal medulla and suggest a novel mechanism of sensitization
      of cutaneous nociceptors.

PMID- 9526022
TI  - Rats with fimbria-fornix lesions are impaired in path integration: a role for the
      hippocampus in "sense of direction".
AB  - Animals can locate their present position in relation to a starting point and
      return to that starting point using cues generated by self-movement, a navigation
      strategy called dead-reckoning. Because contemporary research on spatial
      navigation suggests that some aspects of spatial navigation depend on the
      integrity of the hippocampal formation, whereas others do not, the present study
      examined whether dead-reckoning is hippocampally dependent. The task capitalized
      on the proclivity of foraging rats to carry large food pellets to a shelter for
      eating. Control rats and rats with fimbria-fornix (FF) lesions left a hidden
      burrow to search for one piece of food located somewhere on a circular table. The
      accuracy with which they returned to the burrow with the food was measured. In
      three experiments, rats received probe trials in which they (1) started from
      novel locations, (2) wore blindfolds to obscure visual cues, and (3) foraged
      under a condition in which surface cues, e.g., odors left by their outward
      searches, were displaced. Both sighted control and FF rats preferentially used
      visual cues for guidance when foraging from a familiar location. Control rats
      were accurate and FF rats were impaired in returning to novel starting locations
      (1) when sighted, (2) when blindfolded, and (3) when blindfolded in tests in
      which surface cues were displaced. These results, as well as detailed
      observations on the behavior of the animals, are consistent with the hypothesis
      that rats can use dead-reckoning to solve spatial problems, and this ability
      depends on the integrity of the hippocampal formation.

PMID- 9526023
TI  - A distinct subgroup of small DRG cells express GDNF receptor components and GDNF
      is protective for these neurons after nerve injury.
AB  - Several lines of evidence suggest that neurotrophin administration may be of some
      therapeutic benefit in the treatment of peripheral neuropathy. However, a third
      of sensory neurons do not express receptors for the neurotrophins. These neurons
      are of small diameter and can be identified by the binding of the lectin IB4 and
      the expression of the enzyme thiamine monophosphatase (TMP). Here we show that
      these neurons express the receptor components for glial-derived neurotrophic
      factor (GDNF) signaling (RET, GFRalpha-1, and GFRalpha-2). In lumbar dorsal root
      ganglia, virtually all IB4-labeled cells express RET mRNA, and the majority of
      these cells (79%) also express GFRalpha-1, GFRalpha-2, or GFRalpha-1 plus
      GFRalpha-2. GDNF, but not nerve growth factor (NGF), can prevent several axotomy
      induced changes in these neurons, including the downregulation of IB4 binding,
      TMP activity, and somatostatin expression. GDNF also prevents the slowing of
      conduction velocity that normally occurs after axotomy in a population of small
      diameter DRG cells and the A-fiber sprouting into lamina II of the dorsal horn.
      GDNF therefore may be useful in the treatment of peripheral neuropathies and may
      protect peripheral neurons that are refractory to neurotrophin treatment.

PMID- 9526024
TI  - Pharmacological specialization of learned auditory responses in the inferior
      colliculus of the barn owl.
AB  - Neural tuning for interaural time difference (ITD) in the optic tectum of the owl
      is calibrated by experience-dependent plasticity occurring in the external
      nucleus of the inferior colliculus (ICX). When juvenile owls are subjected to a
      sustained lateral displacement of the visual field by wearing prismatic
      spectacles, the ITD tuning of ICX neurons becomes systematically altered; ICX
      neurons acquire novel auditory responses, termed "learned responses," to ITD
      values outside their normal, pre-existing tuning range. In this study, we
      compared the glutamatergic pharmacology of learned responses with that of normal
      responses expressed by the same ICX neurons. Measurements were made in the ICX
      using iontophoretic application of glutamate receptor antagonists. We found that
      in early stages of ITD tuning adjustment, soon after learned responses had been
      induced by experience-dependent processes, the NMDA receptor antagonist D, L-2
      amino-5-phosphonopentanoic acid (AP-5) preferentially blocked the expression of
      learned responses of many ICX neurons compared with that of normal responses of
      the same neurons. In contrast, the non-NMDA receptor antagonist 6-cyano-7
      nitroquinoxaline-2,3-dione (CNQX) blocked learned and normal responses equally.
      After long periods of prism experience, preferential blockade of learned
      responses by AP-5 was no longer observed. These results indicate that NMDA
      receptors play a preferential role in the expression of learned responses soon
      after these responses have been induced by experience-dependent processes,
      whereas later in development or with additional prism experience (we cannot
      distinguish which), the differential NMDA receptor-mediated component of these
      responses disappears. This pharmacological progression resembles the changes that
      occur during maturation of glutamatergic synaptic currents during early
      development.

PMID- 9526025
TI  - Overtraining does not mitigate contextual fear conditioning deficits produced by
      neurotoxic lesions of the basolateral amygdala.
AB  - The influence of overtraining on the magnitude of fear-conditioning deficits
      produced by neurotoxic lesions of the basolateral amygdala (BLA) was examined.
      Either 1 d before or 1 week after the administration of neurotoxic BLA lesions,
      rats received either 1 or 25 conditioning trials consisting of the delivery of
      unsignaled foot shock in a novel observation chamber; freezing served as the
      measure of conditional fear. In this conditioning paradigm, asymptotic
      performance is reached in five conditioning trials, and 25 conditioning trials
      constitutes an overtraining procedure. The results revealed that overtraining
      does not affect the magnitude of the contextual freezing deficits produced by
      post-training BLA lesions. Similarly, overtraining did not influence the level of
      reacquisition obtained by rats with post-training BLA lesions after 10
      reacquisition trials. A similar pattern of results was observed in rats with
      pretraining BLA lesions. Neurotoxic BLA lesions did not alter either motor
      activity or shock reactivity. These results indicate that overtraining does not
      limit the important role of the BLA in the acquisition and expression of
      contextual fear conditioning.

PMID- 9526027
TI  - Tyrosine YZ and YD of photosystem II . Comparison of optical spectra to those of
      tyrosine oxidised by pulsed radiolysis
AB  - We have compared the optical spectrum of tyrosine oxidised in aqueous solution by
      pulsed radiolysis with spectra of redox active tyrosines YZ and YD of photosystem
      II. This indicates a "tyrosinate" state for these tyrosines and also casts doubt
      on the assumption that YZ and YD optical spectra are very similar in different
      photosystem II preparations. It suggests that further optical spectra of YZ in
      more intact oxygen-evolving preparations are needed before the role of Yz in
      water oxidation can be clarified. Copyright 1998 Elsevier Science B.V.

PMID- 9526026
TI  - Comparison of mesocorticolimbic neuronal responses during cocaine and heroin self
      administration in freely moving rats.
AB  - To compare neuronal activity within the mesocorticolimbic circuit during the self
      administration of cocaine and heroin, multiple-channel single-unit recordings of
      spike activity within the rat medial prefrontal cortex (mPFC) and nucleus
      accumbens (NAc) were obtained during the consecutive self-administration of
      cocaine and heroin within the same session. The variety of neuronal responses
      observed before the lever press are termed anticipatory responses, and those
      observed after the lever press are called post-drug infusion responses. For the
      total of the 110 mPFC and 111 NAc neurons recorded, 30-50% of neurons, depending
      on the individual sessions, had no alteration in spike activity in relation to
      either cocaine or heroin self-administration. Among the neurons exhibiting
      significant neuronal responses during a self-administration session, only a small
      portion (16-25%) of neurons responded similarly under both reinforcement
      conditions; the majority of neurons (75-84%) responded differently to cocaine and
      heroin self-administration as revealed by variations in both anticipatory and/or
      post-drug infusion responses. A detailed video analysis of specific movements to
      obtain the self-administration of both drugs provided evidence against the
      possibility that locomotive differences contributed to the observed differences
      in anticipatory responses. The overall mean activity of neurons recorded in mPFC
      and NAc measured across the duration of the session segment for either cocaine or
      heroin self-administration also was different for some neurons under the two
      reinforcement conditions. This study provides direct evidence that, in mPFC and
      NAc, heterogeneous neuronal circuits mediate cocaine and heroin self
      administration and that distinct, but overlapping, subpopulations of neurons in
      these areas become active during operant responding for different reinforcers.

PMID- 9526028
TI  - Calretinin gene expression in the human thalamus.
AB  - The localization and levels of expression of the calcium-binding protein
      calretinin (CR) in the human thalamus was studied with an in situ hybridization
      method applied to formalin-fixed postmortem material from normal individuals. The
      riboprobe used was generated from a specific fragment of human CR cDNA. As
      visualized on X-ray film autoradiographs, high levels of CR gene transcript
      occurred in several thalamic nuclei, including the reticular nucleus, mediodorsal
      nucleus, rostral intralaminar nuclei (paracentral, central medial and central
      lateral) and several midline nuclei (paraventricular, reuniens and medioventral
      nuclei). In the reticular nucleus, neurons expressing CR mRNA were few in number
      but formed dense and widely distributed clusters. In contrast, virtually all
      neurons in the rostral intralaminar and midline nuclei expressed very high levels
      of CR mRNA and formed a prominent rim around the mediodorsal nucleus, which
      contained scattered clusters of labeled neurons. The caudal intralaminar nuclei,
      principally the centromedian nucleus, displayed very few neurons expressing CR
      mRNA. Only the medial part of the parafascicular nucleus expressed moderate
      levels of CR mRNA. The nuclei of the ventral group (ventral anterior, lateral and
      posterior nuclei) were virtually devoid of CR gene transcript. This highly
      heterogeneous pattern of mRNA expression suggests that CR may be heavily involved
      in the function of the so-called non-specific nuclei, but not in that of the
      specific relay nuclei of the human thalamus. The data also demonstrate that the
      presence of CR gene transcript can easily be detected on formalin-fixed sections
      of the human brain.

PMID- 9526030
TI  - Effect of phosphate residue of NADPH on the interaction between catalytic domains
      of a multifunctional polyketide synthetic enzyme 6-hydroxymellein synthase
AB  - Association of NADPH with the ketoreducing domain of 6-hydroxymellein synthase, a
      multifunctional polyketide synthetic enzyme of carrot, evoked the alternation of
      microstructure around the primary binding site of the co-substrates acetyl- and
      malonyl-CoAs, and this resulted in the marked decrease in Km value of the enzyme
      protein for acetyl-CoA. In contrast, the enzyme did not show the increase in the
      affinity to the substrate when NADPH was replaced by NADH. These results suggest
      that the phosphate residue attached to 2'-position of adenosyl moiety of NADPH
      molecule plays an important role in the co-operative interaction between these
      functional domains of the synthase. Copyright 1998 Elsevier Science B.V.

PMID- 9526029
TI  - Repeated exposure to methylenedioxymethamphetamine (MDMA) alters nucleus
      accumbens neuronal responses to dopamine and serotonin.
AB  - The purpose of this experiment was to investigate the effects of repeated
      exposure to methylenedioxymethamphetamine (MDMA) on responses of neurons in the
      nucleus accumbens of anesthetized rats to microiontophoretically-applied dopamine
      and serotonin. In tests conducted 1-4 days or 9-15 days following the last
      injection of MDMA (20 mg/kg, s.c., twice daily for 4 days), the inhibitory
      effects of both dopamine and serotonin on glutamate-evoked firing of nucleus
      accumbens cells were significantly attenuated compared to effects in control rats
      that were pretreated with saline injections. The inhibitory effect of the D1
      receptor agonist SKF38393 was also significantly attenuated in the MDMA
      pretreated rats. In contrast, the amount of inhibition of glutamate-evoked firing
      produced by application of GABA did not significantly differ between the MDMA
      pretreated and the saline-pretreated rats. The neurotoxicity of the MDMA
      treatment regimen was confirmed by demonstrating that 3H-paroxetine binding was
      significantly decreased in the medial prefrontal cortex and the nucleus accumbens
      of the MDMA-pretreated rats. The mechanisms that produce the attenuated
      inhibitory responses to dopamine and serotonin following repeated injections of
      MDMA are not known. However, the results of these experiments indicate that
      repeated MDMA administration induces long-lasting changes in dopaminergic as well
      as serotonergic neurotransmission in the nucleus accumbens.

PMID- 9526031
TI  - Effect of reserpine on 3-methoxy-4-hydroxyphenylethyleneglycol and 3,4
      dihydroxyphenylacetic acid in the hippocampus of depression-model rats: an in
      vivo microdialysis study.
AB  - Using in vivo microdialysis, we examined the effect of intraperitoneal injection
      of reserpine (2 mg/kg) on hippocampal 3-methoxy-4-hydroxyphenylethyleneglycol
      (MHPG) and 3,4-dihydroxy-phenylacetic acid (DOPAC), two major metabolites of
      catecholamine. Responses were examined serially for 12 h in the hippocampus of
      walking-stress-induced depression-model rats, recovery rats and control rats.
      Control rats showed a rapid rise followed by a gradual fall of free and total
      MHPG and a delayed increase of DOPAC in response to reserpine. Depression-model
      rats showed a significantly blunted biphasic response of free and total MHPG as
      well as blunted monophasic response of DOPAC compared with control rats. Recovery
      rats also exhibited a blunted fall response of MHPG. Our findings suggest that
      the vesicle membrane in the central noradrenaline (NA) neurons could be
      hyposensitive to reserpine in the depression-model rats.

PMID- 9526032
TI  - Ferrocyanide-peroxidase activity of cytochrome c oxidase
AB  - Redox interaction of mitochondrial cytochrome c oxidase (COX) with
      ferrocyanide/ferricyanide couple is greatly accelerated by polycations, such as
      poly-l-lysine [Musatov et al. (1991) Biological Membranes 8, 229-234]. This has
      allowed us to study ferrocyanide oxidation by COX at very high redox potentials
      of the ferrocyanide/ferricyanide couple either following spectrophotometrically
      ferricyanide accumulation or measuring proton uptake associated with water
      formation in the reaction. At low [ferrocyanide]/[ferricyanide] ratios (Eh values
      around 500 mV) and ambient oxygen concentration, the ferrocyanide-oxidase
      activity of COX becomes negligibly small as compared to the reaction rate
      observed with pure ferrocyanide. Oxidation of ferrocyanide under these
      conditions, is greatly stimulated by H2O2 or ethylhydroperoxide indicating
      peroxidatic reaction involved. The ferrocyanide-peroxidase activity of COX is
      strictly polylysine-dependent and is inhibited by heme a3 ligands such as KCN and
      NaN3. Apparently the reaction involves normal electron pathway, i.e. electron
      donation through CuA and oxidation via heme a3. The peroxidase reaction shows a
      pH-dependence similar to that of the cytochrome c oxidase activity of COX. When
      COX is preequilibrated with excess H2O2, addition of ferrocyanide shifts the
      initial steady-state concentrations of the Ferryl-Oxo and Peroxy compounds
      towards approximately 2:1 ratio of the two intermediates. It is suggested that in
      the peroxidase cycleferrocyanide donates electrons to both P and F intermediates
      with a comparable efficiency. Isolation of a partial redox activity of COX opens
      a possibility to study separately proton translocation coupled to the peroxidase
      half-reaction of the COX reaction cycle. Copyright 1998

PMID- 9526033
TI  - [3H]MK-801 binding and the mRNA for the NMDAR1 subunit of the NMDA receptor are
      differentially distributed in human and rat forebrain.
AB  - The distributions of [3H]MK-801 binding and the NMDA NR1 subunit mRNA were
      studied using receptor autoradiography and in-situ hybridization in rat and human
      brain whole-hemisphere coronal sections. Receptor protein detected by radioligand
      autoradiography and the mRNA for the key subunit of the receptor presented
      similar distributions in the forebrain, with a few areas showing an imbalance
      between the levels of mRNA and receptor protein. Human frontal cortex showed a
      relative abundance of NMDAR1 mRNA as compared to [3H]MK-801 binding. The same
      area in rat brain did not show any difference in the two distributions. In
      comparison, the rat claustrum presented a relative excess of NMDAR1 mRNA which
      was not detected in human sections. Human caudate nucleus exhibited relatively
      high levels of [3H]MK-801 binding that were unmatched in rat caudate. The
      hippocampi of either species presented similar levels of [3H]MK-801 binding and
      NMDAR1 mRNA, but when the two signals were measured in specific subfields of the
      hippocampal formation, the differential distribution of the two signals reflected
      the anatomy of hippocampal connections assuming a preferential dendritic
      distribution for MK-801 binding. Interestingly, rat and human hippocampi also
      showed some important species-dependent difference in the relative distribution
      of the receptor protein and mRNA. The data presented show an overall good
      correlation between the mRNA for the key subunit of the NMDA receptor and the
      functional receptor detected with radioligand binding and highlight the presence
      of local differences in their ratio. This may reflect different splicing of the
      mRNA for the NMDAR1 subunit in specific brain areas of rat and human. The species
      dependent differences in the relative distribution of the mRNA for the key
      subunit of the NMDA receptor and that of a marker of functional receptors also
      highlights important differences in the NMDA function in rat and human brain.

PMID- 9526034
TI  - Morphological analysis of cat masseteric motoneurons after intracellular staining
      with horseradish peroxidase.
AB  - Intracellular injection of horseradish peroxidase (HRP) into 58 masseteric
      motoneurons identified by antidromic activation was performed in cats under
      pentobarbital anesthesia. Monosynaptic EPSPs were evoked by masseteric nerve
      stimuli in 52 cells, and were absent in the remaining six cells. The antidromic
      nature of the evoked spikes was confirmed by IS-SD separation observed at high
      frequency (50 Hz) stimulation. Motoneurons with monosynaptic excitation from
      masseter afferents showed IPSPs following stimulation of lingual and inferior
      alveolar nerves. Motoneurons which did not show monosynaptic excitation from
      masseter afferents showed no IPSPs from the above nerves. There were no
      differences in cell size or the number of stem dendrites between motoneurons with
      and without monosynaptic EPSPs. No recurrent collaterals were observed in any
      motor axons. Motoneurons with monosynaptic EPSPs were located at all rostrocaudal
      levels throughout the trigeminal motor nucleus, whereas motoneurons without such
      EPSPs were encountered only at the middle level. Dendrites of motoneurons with
      monosynaptic EPSPs did not extend into the medial portion of the nucleus where
      motoneurons innervating the anterior belly of the digastric muscle were located.
      In contrast, motoneurons without monosynaptic EPSPs had dendrite branches
      extending well into the medial part. The results show that there are two
      subpopulations of masseteric motoneurons that differ in peripheral inputs as well
      as dendritic morphology.

PMID- 9526036
TI  - Intramolecular electron transport in quinoprotein alcohol dehydrogenase of
      Acetobacter methanolicus: a redox-titration study
AB  - Quinohemoprotein-cytochrome c complex alcohol dehydrogenase (ADH) of acetic acid
      bacteria consists of three subunits, of which subunit I contains pyrroloquinoline
      quinone (PQQ) and heme c, and subunit II contains three heme c components. The
      PQQ and heme c components are believed to be involved in the intramolecular
      electron transfer from ethanol to ubiquinone. To study the intramolecular
      electron transfer in ADH of Acetobacter methanolicus, the redox potentials of
      heme c components were determined with ADH complex and the isolated subunits I
      and II of A. methanolicus, as well as hybrid ADH consisting of the subunit I/III
      complex of Gluconobacter suboxydans ADH and subunit II of A. methanolicus ADH.
      The redox potentials of hemes c in ADH complex were -130, 49, 188, and 188 mV at
      pH 7.0 and 24, 187, 190, and 255 mV at pH 4.5. In hybrid ADH, one of these heme c
      components was largely changed in the redox potential. Reduced ADH was fully
      oxidized with potassium ferricyanide, while ubiquinone oxidized the enzyme
      partially. The results indicate that electrons extracted from ethanol at PQQ site
      are transferred to ubiquinone via heme c in subunit I and two of the three hemes
      c in subunit II. Copyright 1998 Elsevier Science B.V.

PMID- 9526035
TI  - Role of carboxyl terminus of mu-and delta-opioid receptor in agonist-induced down
      regulation.
AB  - Chronic exposure of mu-and delta-opioid receptors to their agonists leads to
      different rates in receptor down-regulation. In order to analyze the role of the
      carboxyl terminus of mu-and delta-opioid receptors in the difference in the rate
      of down-regulation, two chimeras of these receptors were generated by swapping
      the carboxyl termini; MORTAGDT and DORTAGMT. These chimeras were tagged at the N
      terminus with hemagglutinin (HA) epitope (YPYDVPDYA), which can be recognized by
      the monoclonal antibody 12CA5, and then stably expressed in Neuro 2A (N2A) cells.
      The swapping of the carboxyl termini did not alter the ligand selectivity of
      these receptor chimeras. However, they did exhibit a reduction in agonist potency
      to inhibit forskolin-stimulated adenylyl cyclase activity for all agonists tested
      except etorphine which had a potency comparable to that of wild type receptors.
      Treatment of the N2A cells expressing MORTAGDT with 50 nM etorphine produced a
      faster rate of receptor down-regulation when compared to the wild type mu-opioid
      receptor. Immunofluorescence microscopy of the MORTAGDT chimera using a
      monoclonal antibody against HA confirmed internalization of the receptors after
      treatment with etorphine for 1 and 6h. There was a reduction in the HA
      immunoreactivity at the cell surface of the MORTAGDT chimera concurrent with more
      noticeable HA-immunoreactivity inside the cell compared to the wild type
      receptor. On the other hand, the rate of down-regulation of DORTAGMT receptors
      was seen to be the same as the wild type delta-opioid receptor after etorphine
      treatment. Immunofluorescence studies showed more reduction in cell surface
      staining of the DORTAGMT chimera compared to the wild type receptor. These data
      suggest the involvement of the carboxyl terminus in agonist-induced down
      regulation and internalization of the nu-opioid receptor. However, different
      mechanisms that are unrelated to the carboxyl terminus may operate in the down
      regulation of delta-opioid receptor.

PMID- 9526037
TI  - Opioid receptor modulation of feeding-evoked dopamine release in the rat nucleus
      accumbens.
AB  - Feeding is associated with increases in the activity of the mesolimbic dopamine
      (DA) system which originates in the ventral tegmental area (VTA) and projects
      heavily to the nucleus accumbens. The present study used in vivo brain
      microdialysis to assess the contribution of opioid receptors in feeding-evoked DA
      release in the nucleus accumbens. Feeding in 18 h food-deprived rats increased DA
      release by about 50% above baseline. Systemic injection of the opioid receptor
      antagonist naltrexone (1 mg/kg, s.c.) blocked the effect of feeding on DA release
      and reduced the amount of food consumed. Unilateral application of naltrexone
      (100 microM) in the VTA via a microdialysis probe failed to affect the DA
      response to feeding, the amount of food consumed, or the latency to eat. In
      contrast, intra-VTA naltrexone significantly reduced the effect of systemic
      heroin (0.5 mg/kg, s.c.) on accumbal DA release. These results indicate that: (1)
      opioid receptor activation is a component of the neural substrates of deprivation
      induced feeding: (2) opioid receptors in the VTA do not contribute significantly
      to feeding-associated increases in DA release in the nucleus accumbens; and (3)
      heroin-induced increases in accumbal DA release are mediated, at least in part,
      by opioid receptors in the VTA.

PMID- 9526038
TI  - Increase of glial fibrillary acidic protein fragments in the spinal cord of motor
      neuron degeneration mutant mouse.
AB  - We analyzed protein fractions extracted from the spinal cord of the motor neuron
      degeneration (Mnd) mouse, a mutant that exhibits progressive degeneration of
      lower spinal motor neurons, by one- and two-dimensional polyacrylamide gel
      electrophoresis (PAGE) after solubilization of the tissue with medium containing
      sodium dodecyl sulfate (SDS)-urea during growth of the animal, in comparison with
      those of age-matched controls (C57BL/6). Several protein spots were detected
      around a region of pI 5.6-6.0 and molecular mass of 35-50 kDa in Mnd spinal cord
      tissue on the two-dimensional PAGE separation profile with Coomassie brilliant
      blue staining, while only a few spots around the same region were found in the
      control spinal cord. These spots were all immunoreactive with an antibody against
      glial fibrillary acidic protein (GFAP), a cytoskeleton filamentous protein
      specific to astroglial cells. The protein spot with molecular mass of 50 kDa
      showed immunoreactivity with anti-GFAP antibody, had a blocked amino-terminus,
      and is assumed to be intact GFAP. Several protein spots with slightly smaller
      molecular masses of 35 to 48 kDa lacked the head domain of the GFAP molecule as a
      result of cleavage at the 29th and 56th residues from the amino terminus. In Mnd
      spinal cord tissue, the densities of the immunoreactive GFAP bands with smaller
      molecular masses increased with development, and became dominant at the time of
      the appearance of behavioral paralytic gait around 6 to 7 months of age. These
      results suggest that the increased GFAPs devoid of head domains are related to
      the degenerative loss of motor neurons in the Mnd spinal cord. Histopathological
      and GFAP immunohistochemical examination of Mnd spinal cord preparation
      demonstrated progressive degenerative loss of motor neurons, and considerable
      increases in number of GFAP-stained astrocytes in the ventral horn at 7 to 9
      months of age. These processes of degenerative loss of motor neurons and
      proliferation of reactive astrocytes with increased levels of fragmented GFAP in
      the Mnd spinal cord during development seem to be characteristic and preceded the
      deterioration of motor activities in this animal model of amyotrophic lateral
      sclerosis.

PMID- 9526040
TI  - Effects of feeding and insulin on extracellular acetylcholine in the amygdala of
      freely moving rats.
AB  - Extracellular levels of acetylcholine (ACh) were measured in the central nucleus
      of the amygdala using microdialysis in 20-min intervals before, during, and after
      1 h feeding in food-deprived rats. The results were compared to the effects of
      peripheral injections of glucose or 'low' (200 mU) and 'high' (1 U) doses of
      insulin. Feeding caused a 40% increase in extracellular ACh in the amygdala
      during the hour-long meal. Acetylcholine returned to baseline 1 h after food was
      removed. Systemic injections of either glucose or insulin in ad libitum fed rats
      also resulted in an increase in ACh levels (+50-60%), but with a different time
      course. Glucose elevated ACh to a plateau within 20 min for an hour's duration;
      whereas both doses of insulin caused a peak in ACh release in the first 20 min
      followed by gradual return to baseline. The 'low' and 'high' doses of insulin had
      similar effects on ACh release even though they had different hypoglycemic
      potency as measured in blood samples. These results suggest that ACh in the AMY
      is involved in feeding and the response to glucose utilization.

PMID- 9526039
TI  - Calpain I activation in rat hippocampal neurons in culture is NMDA receptor
      selective and not essential for excitotoxic cell death.
AB  - Administration of glutamate (100 microM) to primary cultures of rat hippocampal
      neurons for 1 h led to calpain I activation as determined by monitoring the
      extent of spectrin breakdown with the antibodies designed to specifically
      recognize the calpain I-mediated spectrin breakdown products. Based on the
      studies with subtype selective antagonists of glutamate receptors, glutamate
      caused calpain I activation specifically through the activation of the NMDA
      receptor. In parallel experiments, the magnitude and the temporal profiles of
      Ca2+ rise were determined by Fura-2 microfluorimetry. Ca2+ influx through voltage
      sensitive Ca2+ channels, even though leading to substantial Ca2+ rise, did not by
      itself activate calpain I. These results indicate that for calpain I activation,
      the source of Ca1+ influx is more important than the magnitude of Ca2+ rise.
      Glutamate-mediated calpain I activation was fully blocked by preincubation (30
      min) of the cultures with calpain inhibitor I, calpain inhibitor II, or calpeptin
      (all 10 microM). The presence of calpain inhibitors did not, however, in any way
      ameliorate the massive excitotoxicity resulting from 16 h exposure to glutamate,
      indicating that calpain I activation and excitotoxicity are not causally related
      events. Similarly, preincubation with any of the tested calpain inhibitors was
      detrimental to the clearance of neuritic from a 10-min exposure to glutamate.
      Additionally, the presence of calpain inhibitors was detrimental to the clearance
      of neuritic varicosities resulting from a short-term sublethal exposure to
      glutamate, suggesting that a physiological level of calpain I activation might
      actually play an important homeostatic role in the restoration of normal
      cytoskeletal organization.

PMID- 9526041
TI  - The xanthophyll cycle of higher plants: influence of antenna size and membrane
      organization
AB  - The development of the photosynthetic apparatus of intermittent light grown pea
      plants under continuous illumination has been investigated. We determined the
      formation of antenna proteins and the synthesis of pigments at different stages
      of greening and compared the data with the changes in the xanthophyll cycle
      reactions. The limited convertibility of violaxanthin in the de-epoxidation
      reactions of the cycle was found to be closely related to the presence of antenna
      proteins and could be attributed to direct (pigment binding) and indirect (grana
      formation) functions of antenna proteins. The reduced epoxidation rate in
      intermittent light plants was found to be accelerated with increasing amounts of
      antenna proteins. However, the changes in the epoxidation rates were not
      consistent with the assignment of the epoxidase activity to LHC II, the major
      light harvesting complex protein of photosystem II. This interpretation was
      further supported by an unchanged epoxidase activity in - also LHC II depleted -
      bundle sheath cells of the C4 plant Sorghum bicolor and stroma fractions of
      isolated spinach thylakoids. We assume that the basic function of antenna
      proteins in the xanthophyll cycle of higher plants is mainly related to the
      binding of the substrate and/or to interactions with the de-epoxidase/epoxidase.
      By that antenna proteins seem to be responsible for the limited violaxanthin
      convertibility as well as they are required for highest epoxidation rates.
      Copyright 1998 Elsevier Science B.V.

PMID- 9526042
TI  - Neurochemical organization of paratrigeminal nucleus projections to the dorsal
      vagal complex in the rat.
AB  - The paratrigeminal nucleus, located in the spinal trigeminal tract rostral to the
      obex, is important in the integration of visceral and somatosensory afferent
      information and may modulate autonomic function through its projections to the
      dorsal vagal complex. Anterograde and retrograde neuroanatomical tracers were
      used in conjunction with immunohistochemistry to determine the neurochemical
      organization of the efferent pathway from the paratrigeminal nucleus to the
      dorsal vagal complex in the rat. Double-labelling studies demonstrated that leu
      enkephalin, 28-kDa calbindin, and neuronal nitric oxide synthase were present in
      neurons in the paratrigeminal nucleus that project to the dorsal vagal complex.
      The results of this study are consistent with the hypothesis that neurochemically
      distinct pathways from the paratrigeminal nucleus are involved in the sensory
      modulation of autonomic function.

PMID- 9526043
TI  - Time-dependent and regional expression of GABA transporter mRNAs following
      amygdala-kindled seizures in rats.
AB  - To investigate the role played by GABA transporters in epileptic seizures, we
      examined time-dependent and regional changes in expression of GAT-1 and GAT-3
      GABA transporter mRNA in amygdala-kindled rat brain using an in situ
      hybridization method. GAT-1 mRNA was significantly increased bilaterally in the
      hippocampal dentate gyrus (111-116%) at 1 h after kindled generalized seizures.
      GAT-1 mRNA was also significantly increased bilaterally in the hippocampal
      subfields (CA1-4 and dentate gyrus [110-117%]) at 4 h after kindled seizures.
      There were no significant changes in GAT-1 mRNA level in the amygdalar nuclei,
      pyriform cortex or cerebral cortex either ipsilaterally or contralaterally at any
      time after kindled seizures. In contrast, GAT-3 mRNA was significantly increased
      bilaterally in the amygdalar nuclei and in the contralateral pyriform cortex and
      cerebral cortex 1 h after seizures. Since all these changes returned to control
      levels by 8 or 24 h after kindled seizures, the increases in GABA transporter
      mRNA appeared to be transient responses to seizure activity. These findings
      indicate that GAT-1 subtype transporter is specifically involved in seizure
      activity in the hippocampus, while GAT-3 subtype transporter is mainly involved
      in seizure activity in the amygdalar nuclei and pyriform cortex following
      amygdala-kindled generalized seizures.

PMID- 9526045
TI  - Confocal laser scanning microscopy used to monitor intracellular Ca2+ changes in
      hippocampal CA 1 neurons during energy deprivation.
AB  - An increase in intracellular calcium during cerebral ischemia has been proposed
      as a common final pathway underlying the events leading to neuronal death.
      Intracellular calcium has been measured with ion selective electrodes during
      energy deprivation (ED) in hippocampal slices and with fluorescent techniques in
      neuronal cultures. In the present study, we describe a novel method to visualize
      and quantify changes in intracellular calcium in brain slices using Confocal
      Laser Scanning Microscopy (CLSM). CA 1 pyramidal neurons in hippocampal slices
      were filled by intracellular injection with a 1:2 mixture of the fluorescent dyes
      Fluo 3 and Fura Red. The neurons were then visualized using CLSM, and the ratio
      of the fluorescence from each probe used to quantify intracellular calcium
      concentrations before and during ED. The free intracellular calcium concentration
      was 60 nM prior to ED and increased to 24 microM during ED. These results
      demonstrates that CLSM and fluorescent probes can be used in functional neuronal
      networks in addition to cell cultures as previously described.

PMID- 9526046
TI  - Reduction of the plastoquinone pool by exogenous NADH and NADPH in higher plant
      chloroplasts. Characterization of a NAD(P)H-plastoquinone oxidoreductase activity
AB  - Chlorophyll fluorescence measurements were performed on osmotically lysed potato
      chloroplasts in order to characterize the reactions involved in the dark
      reduction of photosynthetic inter-system chain electron carriers. Addition of
      NADH or NADPH to lysed chloroplasts increased the chlorophyll fluorescence level
      measured in the presence of a non-actinic light until reaching Fmax, thus
      indicating an increase in the redox state of the plastoquinone (PQ) pool. The
      fluorescence increase was more pronounced when the experiment was carried out
      under anaerobic conditions and was about 50% higher when NADH rather than NADPH
      was used as an electron donor. The NAD(P)H-PQ oxidoreductase reaction was
      inhibited by diphenylene iodonium, N-ethylmaleimide and dicoumarol, but
      insensitive to rotenone, antimycin A and piericidin A. By comparing the substrate
      specificity and the inhibitor sensitivity of this reaction to the properties of
      spinach ferredoxin-NADP+-reductase (FNR), we infer that FNR is not involved in
      the NAD(P)H-PQ oxidoreductase activity and conclude to the participation of
      rotenone-insensitive NAD(P)H-PQ oxidoreductase. By measuring light-dependent
      oxygen uptake in the presence of DCMU, methyl viologen and NADH or NADPH as an
      electron donors, the electron flow rate through the NAD(P)H-PQ oxidoreductase is
      estimated to about 160 nmol O2 min-1 mg-1 chlorophyll. The nature of this enzyme
      is discussed in relation to the existence of a thylakoidal NADH dehydrogenase
      complex encoded by plastidial ndh genes. Copyright 1998 Elsevier Science B.V.

PMID- 9526044
TI  - Calbindin-D28k buffers intracellular calcium and promotes resistance to
      degeneration in PC12 cells.
AB  - The calcium-binding protein calbindin-D28k (CB) has been hypothesized to
      function, in part, as a neuroprotective protein. CB is localized within nerve
      cells that are often less vulnerable to degeneration in patients with Alzheimer's
      disease and Parkinson's disease, and cells containing CB can buffer intracellular
      calcium concentrations ([Ca2+]i). The present study was designed to directly test
      the hypothesis that CB can protect cells from degeneration by reducing [Ca2+]i.
      PC12 cells, transfected to express different levels of CB, were found to be
      significantly less vulnerable to degeneration caused by serum withdrawal,
      glutamate, and the neurotoxin 1-methyl-4-phenylpyridinium (MPP+). However, CB did
      not protect cells from degeneration caused by the calcium ionophore A23187. CB
      transfected cells exhibited reduced elevations in [Ca2+]i following treatment
      with bradykinin, or ATP compared to non-CB-containing cells. These data indicate
      that CB can protect cells from degeneration caused by certain conditions, and it
      reduces elevations in [Ca2+]i caused by influx from extracellular sources.

PMID- 9526047
TI  - Serotonergic regulation of neuropeptide and glutamic acid decarboxylase mRNA
      levels in the rat striatum and globus pallidus: studies with fluoxetine and DOI.
AB  - The serotonergic regulation of neuropeptide and glutamic acid decarboxylase (GAD)
      mRNA level in the rat basal ganglia was investigated by determining the effects
      of chronic treatment with the serotonin uptake blocker fluoxetine and the
      serotonin 5-HT2 agonist (+/-)-2,5-dimethoxy-4-iodoamphetamine hydrobromide (DOI).
      Fluoxetine (10 mg/kg) induced a reduction of preproenkephalin and GAD65 mRNA
      levels in the caudate-putamen and nucleus accumbens core and shell after 5 days
      of treatment. In addition, GAD65 mRNA levels were reduced in the globus pallidus.
      These changes appeared to be transient as they were not found after 15 days of
      fluoxetine treatment. DOI (7 mg/kg), administered for 9 days, induced a decrease
      of preprodynorphin mRNA levels in the caudate-putamen and the nucleus accumbens
      core and shell. No regional differentiation in the effects of fluoxetine and DOI
      was observed. Based on the present results, we propose that an increased 5-HT
      tone may reduce enkephalin and GABA mRNA levels in striatal regions and in the
      globus pallidus. Our results further show that preproenkephalin mRNA is not
      affected by chronic 5-HT2 receptor stimulation, indicating that the fluoxetine
      induced decrease in preproenkephalin mRNA levels involves other 5-HT receptors
      than the 5-HT2 receptor. Preprodynorphin mRNA levels, on the other hand, were
      found to be reduced after chronic 5-HT2 receptors than stimulation. This
      observation, together with our previous finding that the 5-HT2 antagonist
      ritanserin tends to increase preprodynorphin mRNA levels, suggests a 5-HT2
      mediated tonic inhibition of preprodynorphin mRNA levels.

PMID- 9526049
TI  - Unisite ATP hydrolysis by soluble Rhodospirillum rubrum F1-ATPase is accelerated
      by Ca2+
AB  - At saturating concentrations of ATP, soluble F1 from the Rhodospirillum rubrum
      (RF1) exhibits a higher rate of hydrolysis with Ca2+ than with Mg2+. The
      mechanisms involved in the expression of a higher catalytic activity with Ca2+
      were explored by measuring the ATPase activity of RF1 at substiochiometric
      concentrations of ATP (unisite conditions). At a ratio of 0.25 [gamma-32P]ATP per
      RF1, the enzyme exhibited a 50 times higher hydrolytic rate with Ca2+ than with
      Mg2+. The rate of [gamma-32P]ATP binding to RF1 was in the same range with the
      two divalent metal ions. Centrifugation-filtration of RF1 exposed to
      substoichiometric [gamma-32P]ATP concentrations and Mg2+ through Sephadex columns
      yielded an enzyme that contained [gamma-32P]ATP and [32P]phosphate in a
      stoichiometry that was close to one. In the presence of Ca2+, the eluted enzyme
      did not contain [gamma-32P]ATP nor [32P]phosphate. This indicated that the rate
      of product release was faster with Ca2+ than with Mg2+. It was also observed that
      the ratio of multisite to unisite hydrolysis rates was of similar magnitude with
      both divalent cations. This suggests that they do not affect differently the
      cooperative mechanisms that may exist between catalytic sites. In consequence,
      the higher ATPase activity of RF1 in presence of Ca2+ strongly suggests that the
      retention time of products is decreased in the presence of this cation. Copyright
      1998 Elsevier Science B.V.

PMID- 9526048
TI  - Stimulation-induced responses of the trigeminal caudal neurons in the brainstem
      preparation isolated from newborn rats.
AB  - The brainstem preparation with the trigeminal mandibular nerve attached was
      isolated from rats postnatal day 0-6 (P0-P6) to test if the potentiation could be
      induced in neonatal neurons in the trigeminal subnucleus caudalis by stimulation
      of the primary afferents. The stimulation-induced potentials in 92 neurons
      recorded extracellularly, and the synaptic potentials in 16 neurons recorded by
      the whole-cell patch clamp technique were examined. The extracellularly recorded
      neurons responded to stimulation (0.5 Hz) with either an increase, a decrease, or
      little change in spike numbers, and were classified as Type 1, Type 2, and Type
      3, respectively. Type 1 neurons at P4 and older responded in a low Mg2+ solution
      with a progressive increase in spike number lasting for several minutes after the
      cessation of stimulation, i.e., short-term potentiation, STP. This potentiation
      was antagonized by 20 microM of (+)-MK-801 hydrogen maleate (MK-801) or 25 microM
      of 2-amino-5-phosphonovaleric acid. In contrast, Type 1 at P3 and younger did not
      exhibit STP. The age-related distinct response properties were observed between
      Type 1 neurons at P4-P6 and at P0-P3. The percentage of Type 1 in studied neurons
      increased from 24% at P0-P3 to 53% at P4-P6. In the intracellular experiment, the
      mean latency of excitatory postsynaptic potential (EPSP) of recorded neurons
      indicated that the conduction velocity of the convergent afferents was 0.37 m/s,
      in the range of C-fiber. Neurons were classified as Type E and Type I. Type E
      responded with EPSP only, or with both EPSP and inhibitory postsynaptic
      potentials (IPSP), while Type I responded with IPSP only. In Type E at P4 and
      older, a single stimulation produced a burst of spike discharges that lasted for
      several seconds. Stimulation at a hyperpolarized membrane potential showed that
      aggregated slow EPSPs lay under a burst of spike discharges, and that slow EPSPs,
      but not a short-latency EPSP, were completely blocked by MK-801. In contrast,
      Type E at P3 and younger did not evoke a burst of spikes. Morphological
      examination of recorded neurons showed that the formation of networks was sparse
      at P1 and rapidly developed up to P4. The results suggest that: (1) short-term
      potentiation is induced with the development of synaptic network formation in the
      caudal nucleus at P4 and older; (2) the summation of N-methyl-d-aspartate (NMDA)
      mediated slow EPSPs build up a prolonged depolarization; and (3) the brainstem
      preparation is applicable for neurophysiological studies on the trigeminal pain
      system.

PMID- 9526050
TI  - Retinoic acid regulates gonadotropin-releasing hormone (GnRH) release and gene
      expression in the rat hypothalamic fragments and GT1-1 neuronal cells in vitro.
AB  - The present study attempts to examine the possible involvement of retinoic acid
      (RA) in the regulation of gonadotropin-releasing hormone (GnRH) release and gene
      expression in the rat hypothalamic fragments and GT1-1 neuronal cells in vitro.
      During a short-term period (2h), RA (0.01-1 microM) increased GnRH release in a
      dose-related manner. Time-course experiments showed that RA rapidly increased
      GnRH release by 30 min in both cells. RA-induced GnRH release was slowly
      attenuated in the next incubation period in hypothalamic fragments, but rapidly
      returned to control levels in GT-1 cells. In hypothalamic fragments, GnRH mRNA
      levels decreased, but in GT1-1 cells, no change in GnRH mRNA levels was observed.
      We then extended the incubation time to see any changes in GnRH mRNA levels by RA
      in GT1-1 cells. In a long term (up to 48 h), RA increased GnRH mRNA levels in a
      dose- and time-related manner. Significant increase in GnRH mRNA levels by RA (at
      higher than 10 nM) was observed within 12h. Transient transfection experiments
      with a luciferase reporter vector containing more than 3 kb of the rat GnRH 5'
      flanking region (-3002 to +88) revealed that RA also increased the rat GnRH
      promoter activity in a similar dose-and time-dependent manner, suggesting that
      increases in GnRH mRNA levels are attributable, at least in part, to the enhanced
      gene transcription. The promoter analysis with the 5'-deletional constructs
      demonstrated that cis-elements responsible for the RA action may reside within 
      1640/-1438 of the rat GnRH promoter, where multiple direct or palindromic
      arrangements of the AGGTCA-related sequences exist. We also showed that GT1-1
      cells as well as the hypothalamic tissues express mRNA for multiple subtypes of
      retinoid receptors, and that reporter plasmids with three copies of the strong
      retinoic acid response element (RARE) were activated by 80 folds upon treatment
      with RA in GT1-1 cells, suggesting that retinoid receptors in GT1-1 cells are
      functional. Taken together, the present study strongly suggests that RA is an
      important regulator of the GnRH neurons.

PMID- 9526051
TI  - Central pressor effect of parathyroid hormone-related protein in conscious rats.
AB  - Although the parathyroid hormone-related protein gene is widely expressed in the
      central nervous system, the role of this protein in blood pressure is unknown.
      This article examines whether parathyroid hormone-related protein is involved in
      the central regulation of blood pressure. An intraventricularly injected solution
      of parathyroid hormone-related protein elicited a dose-dependent increase of mean
      arterial pressure accompanied by a decrease of heart rate in conscious Sprague
      Dawley rats. An anti-parathyroid hormone-related protein monoclonal antibody,
      given in an intraventricularly injected solution, blocked the pressor effect of
      parathyroid hormone-related protein. Furthermore, this pressor effect of
      parathyroid hormone-related protein was also abolished after pretreatment by
      intravenous administration of either hexamethonium bromide or doxazosin mesylate.
      These results suggest that central parathyroid hormone-related protein is
      implicated in the regulation of blood pressure, and that this effect may be
      mediated through sympathetic activation.

PMID- 9526052
TI  - Localization of leptin receptor immunoreactivity in the lean and obese Zucker rat
      brain.
AB  - Leptin, a product of the obese (ob) gene, is secreted by adipocytes and appears
      to act as a hormone to regulate food intake, metabolism and body weight.
      Subcutaneous administration of leptin causes reductions in food intake and body
      and fat-depot weights in both lean and genetically obese (ob/ob) mice, and leptin
      infusion into the lateral cerebral ventricles decreases feeding with short
      latency, suggesting a central site of action. A gene defect in the Zucker obese
      rat causes an amino acid substitution in the leptin receptor and reduced leptin
      binding at the cell surface. An antiserum to a portion of the mouse leptin
      receptor (AA 877-894) located within the intracellular domain was used to label
      Zucker lean (Fa/?) and obese (fa/fa) rat brain sections. At optimal dilution
      (1:8000), only cells in the basal forebrain, preoptic area, hypothalamus and
      brainstem were moderately or intensely labeled. The most intensely-labeled
      nuclei, the anterior commissural, magnocellular paraventricular, supraoptic,
      circularis in the anterior hypothalamus and fornical in the lateral hypothalamus
      contain large neurons that synthesize and secrete vasopressin or oxytocin and
      their respective neurophysins. Diminished leptin transport into the central
      nervous system or defective signal transduction in Zucker obese rats may
      sufficiently compromise leptin regulation of the HPA axis, NPY-immunoreactive
      neurons or other hypothalamic elements to cause obesity.

PMID- 9526053
TI  - Protein synthesis blockade differentially affects the stress-induced
      transcriptional activation of neuropeptide genes in parvocellular neurosecretory
      neurons.
AB  - Corticotropin-releasing factor (CRF) and arginine vasopressin (AVP) are
      synergistically interacting ACTH secretagogues that are co-expressed by
      parvocellular neurosecretory neurons of the hypothalamic paraventricular nucleus
      (PVH). To shed light on the mechanisms that mediate the stress-induced
      transcriptional activation of these neuropeptide genes, quantitative
      hybridization histochemical methods were used to assess the effects of systemic
      treatment with the protein synthesis inhibitor, cycloheximide, on the ether
      stress-induced upregulation of primary CRF and AVP transcripts, in vivo.
      Pretreatment with cycloheximide prevented the induction of FOS, but not CREB
      phosphorylation, normally seen in response to acute ether exposure, and
      significantly attenuated the stress-induced rise in AVP, but not CRF,
      heteronuclear RNA expression in the parvocellular division of the PVH. These
      results support the view that distinct molecular mechanisms govern the expression
      of the two principal corticotropin-releasing factors, in vivo.

PMID- 9526054
TI  - Differences in hypothalamic serotonin between estrous phases and gender: an in
      vivo microdialysis study.
AB  - The aim of the present study was to assess whether there are gender differences
      in (1) levels of extracellular serotonin (5-HT) in the forebrain, and (2) the
      effect on 5-HT of a reuptake inhibitor, paroxetine, or a releasing drug,
      fenfluramine. In vivo microdialysis was used to measure 5-HT in the hypothalamus
      of male and regularly cycling female rats. Hypothalamic 5-HT was significantly
      lower in estrous females (0.83 +/- 0.05 pg/sample, n=33) than in male rats (1.04
      +/- 0.06 pg, n=38). Levels in diestrous females (0.98 +/- 0.09 pg, n=38) were not
      significantly different from males. Paroxetine (1 mg/kg) increased hypothalamic 5
      HT in males, and diestrous and estrous females to approximately 2 pg/sample.
      However, the increase in hypothalamic 5-HT produced by a maximally effective dose
      of paroxetine (10 mg/kg) was significantly greater in male rats and during
      diestrous than during estrous. d,l-Fenfluramine (10 mg/kg) evoked an increase in
      extracellular 5-HT to approximately 15 pg/sample in all groups. A higher dose of
      d,l-fenfluramine (20 mg/kg) produced a significantly greater increase in
      hypothalamic 5-HT in males than in females during estrous or diestrous. These
      results are consistent with other evidence that during estrous, when rats are
      responding to peak levels of estrogen and progesterone, 5-HT release is
      decreased.

PMID- 9526055
TI  - Gene expression studies of mRNAs encoding the NMDA receptor subunits NMDAR1,
      NMDAR2A, NMDAR2B, NMDAR2C, and NMDAR2D following long-term treatment with cis-and
      trans-flupenthixol as a model for understanding the mode of action of
      schizophrenia drug treatment.
AB  - It has been hypothesized that glutamate receptor function is important in both
      the aetiology and treatment of schizophrenia. In order to understand how specific
      glutamate receptor genes are involved in the treatment of schizophrenia we have
      used a multiprobe oligonucleotide solution hybridization (MOSH) technique to
      examine the regulation of gene express of the NMDAR1, 2A, 2B, 2C, 2D receptor
      subunits in the left rat brain following treatment with the optical isomers of
      flupenthixol. cis- and trans-flupenthixol are both present in the commonly used
      oral and depot treatments for schizophrenia and a controlled trial showed that
      cis-flupenthixol had a significantly superior ability to ameliorate the positive
      symptoms of schizophrenia compared to its trans-isomer. At a dose of 0.2
      mg/kg/day over a period of 1, 2, 4, 8, 12 and 24 weeks, we found that both
      isomers down regulated the expression of NMDAR1 mRNA in most regions of the
      brain. NMDAR2A, 2B and 2C receptor subunits showed a significantly decreased
      expression from 12 to 24 weeks but after 2 weeks NMDAR2B, 2C, 2D expression was
      increased in several brain regions. The NMDAR1 receptor subunit immunoreactivity
      in the right brain following 4 and 24 weeks of drug treatment was also examined
      by Western blotting. Both trans- and cis-flupenthixol significantly decreased the
      NR1 immunoreactivity in the right cerebellum after 24 weeks of treatment. These
      results suggest that NMDA receptor subunits may have a role in the action of
      antipsychotic drugs. If we assume that the NMDA receptor expression changes
      reflect a beneficial and significant mechanism in the treatment of schizophrenia,
      it could be argued that NMDA receptor changes are more related to the negative or
      non-specific symptoms of schizophrenia.

PMID- 9526056
TI  - Corrigendum to 'Determination of photochemical loss in leaves by an open-ended
      photothermal cell'

PMID- 9526057
TI  - Neurons in the posterior insular cortex are responsive to gustatory stimulation
      of the pharyngolarynx, baroreceptor and chemoreceptor stimulation, and tail pinch
      in rats.
AB  - Extracellular unit responses to gustatory stimulation of the pharyngolaryngeal
      region, baroreceptor and chemoreceptor stimulation, and tail pinch were recorded
      from the insular cortex of anesthetized and paralyzed rats. Of the 32 neurons
      identified, 28 responded to at least one of the nine stimuli used in the present
      study. Of the 32 neurons, 11 showed an excitatory response to tail pinch, 13
      showed an inhibitory response, and the remaining eight had no response. Of the 32
      neurons, eight responded to baroreceptor stimulation by an intravenous (i.v.)
      injection of methoxamine hydrochloride (Mex), four were excitatory and four were
      inhibitory. Thirteen neurons were excited and six neurons were inhibited by an
      arterial chemoreceptor stimulation by an i.v. injection of sodium cyanide (NaCN).
      Twenty-two neurons were responsive to at least one of the gustatory stimuli
      (deionized water, 1.0 M NaCl, 30 mM HCl, 30 mM quinine HCl, and 1.0 M sucrose);
      five to 11 excitatory neurons and three to seven inhibitory neurons for each
      stimulus. A large number of the neurons (25/32) received converging inputs from
      more than one stimulus among the nine stimuli used in the present study. Most
      neurons (23/32) received converging inputs from different modalities (gustatory,
      visceral, and tail pinch). The neurons responded were located in the insular
      cortex between 2.0 mm anterior and 0.2 mm posterior to the anterior edge of the
      joining of the anterior commissure (AC); the mean location was 1.2 mm (n=28)
      anterior to the AC. This indicates that most of the neurons identified in the
      present study seem to be located in the region posterior to the taste area and
      anterior to the visceral area in the insular cortex. These results indicate that
      the insular cortex neurons distributing between the taste area and the visceral
      area receive convergent inputs from gustatory, baroreceptor, chemoreceptor, and
      nociceptive organs.

PMID- 9526058
TI  - Sequence diversity of voltage-gated potassium channels in an electric fish.
AB  - Cloning of voltage-gated K+ channels has indicated that these channels constitute
      a diverse family of genes that have been subclassified into four closely related
      gene families Kv1-Kv4 (Shaker, Shab, Shaw, Shal). A PCR approach has been used to
      assess the diversity of K+ channels in the weakly electric fish Apteronotus
      leptorhynchus, which is a well studied model of sensory processing. Degenerate
      primers specific for the highly conserved pore and S6 transmembrane domains of
      the K+ channel families were used to amplify an intronless 124 bp fragment from
      fish genomic DNA. DNA sequence analysis of a large number of these fragments has
      identified 19 putative K+ channels, each of which can be classified into one of
      the four major families. Ten fall into Kv1 class, two in the Kv2 class, five in
      the Kv3 class and two in the Kv4 class. The results indicate that the
      duplications that gave rise to multiple genes within each of the K+ channel
      families predate the divergence of the Actinopterygii and Sarcopterygii lineages
      (400 million years ago) during early vertebrate evolution.

PMID- 9526059
TI  - The effect of 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) and charybdotoxin
      (CTX) on relaxations of isolated cerebral arteries to nitric oxide.
AB  - The mechanism underlying smooth muscle relaxations of cerebral arteries in
      response to nitric oxide is still not completely understood. The present study
      was designed to determine the role of soluble guanylate cyclase in the
      relaxations to a nitric oxide/nucleophile complex, diethylaminodiazen-1-ium-1,2
      dioate (DEA-NONOate). Rings of canine middle cerebral arteries without
      endothelium were suspended in Krebs-Ringer bicarbonate solution for isometric
      tension recording. The levels of guanosine 3',5'-cyclic monophosphate (cyclic
      GMP) were measured by radioimmunoassay technique. During contractions to uridine
      5'-triphosphate (UTP), DEA-NONOate (10(-10) to 10(-5) M) caused concentration
      dependent relaxations. Measurements of cyclic GMP levels in cerebral arterial
      wall demonstrated that DEA-NONOate is a potent stimulator of guanylate cyclase
      and subsequent formation of cyclic GMP. Increasing concentrations of a selective
      soluble guanylate cyclase inhibitor, 1H-[1,2,4]-oxadiazolo[4,3-a]quinoxalin-1-one
      (ODQ), caused concentration-dependent reduction of both cyclic GMP production and
      relaxations to DEA-NONOate. Interestingly, in the presence of the highest
      concentration (3 x 10(-6) M) of ODQ, production of cyclic GMP in response to 10(
      6) M of DEA-NONOate was abolished, whereas the same concentration of DEA-NONOate
      caused almost complete relaxation, suggesting that mechanisms independent of
      cyclic GMP production may mediate relaxing effect of high concentration of a
      nitric oxide donor. A selective Ca2+-activated potassium channel blocker
      charybdotoxin (CTX) significantly reduced relaxations to DEA-NONOate resistant to
      ODQ, supporting the idea that in cerebral arteries nitric oxide may activate
      potassium channels independently of cyclic GMP. The results of our study suggest
      that under physiological conditions, guanylate cyclase is a key mediator of
      cerebral arterial relaxations to nitric oxide. However, under pathological
      conditions associated with induction of nitric oxide synthase and increased
      biosynthesis of nitric oxide (e.g., cerebral ischemia, inflammation, sepsis),
      mechanisms other than formation of cyclic GMP may be activated.

PMID- 9526060
TI  - Circadian changes in the expression of vasoactive intestinal peptide 2 receptor
      mRNA in the rat suprachiasmatic nuclei.
AB  - The suprachiasmatic nuclei (SCN) in the hypothalamus function as the primary
      circadian pacemaker. A receptor for vasoactive intestinal peptide (VIP), denoted
      as VIP2, is abundantly expressed in the SCN. Since the rodent circadian clock
      demonstrates phase-dependent sensitivity to exogenous VIP, we investigated the
      possibility that VIP2 receptor mRNA is differentially expressed in the SCN across
      the 24 h cycle. To establish whether VIP2 receptor mRNA levels change across the
      12:12 h light-dark (LD) cycle (lights on designated as Zeitgeber time (ZT)O),
      rats were killed at ZT 0, 2, 6, 10, 12, 14, 18 and 22. To determine if variation
      in this mRNA occurs in the absence of LD entrainment cues, lights were not turned
      on at the time of transition from dark to light (designated as CT O); the animals
      in this group were killed in constant darkness (DD) at CT 0, 2, 6, 10, 12, 14, 18
      and 22. In situ hybridization histochemistry indicated no variations in VIP2
      receptor mRNA in the cingulate cortex under either LD or DD conditions. There
      was, however, significant variation in the expression of VIP2 receptor mRNA
      within the SCN during the LD cycle, with one peak at ZT 6 and at ZT 22. A
      comparable biphasic pattern of mRNA expression was observed in DD animals with
      peaks at CT 10 and another at CT 22. The results suggest that the phase-dependent
      actions of VIP on the clock may involve phase-specific changes in the
      availability of VIP2 receptor within the SCN.

PMID- 9526061
TI  - Molecular cloning and characterization of a human brain-specific gene implicated
      in neuronal differentiation.
AB  - A 2.5 kb human cDNA clone containing a CAG trinucleotide repeat, designated HB20,
      was isolated from a human fetal brain library. Northern analysis on multi-tissue
      blots and various cell lines confirmed that HB20 is specifically expressed in the
      brain. Its expression is low in two glioma cells, moderate in a neuron precursor
      cell, NT2, but absent in lymphoma, cervical carcinoma, or colonic carcinoma
      cells. Significant increase of HB20 mRNA was shown along with retinoic acid
      induced terminal differentiation of NT2 cells into neuron cells, hNT. Homology
      comparison of the predicted HB20 amino acid sequence with the current database
      revealed that it belongs to a newly recognized protein family composed of
      nucleosome assembly proteins and SET proto-oncogene, which has been shown to
      interact specifically with B-type cyclins involved in the control of cell
      proliferation. Together with the detection of nuclear localization signals and
      apparent nuclear distribution of expressed protein, HB20 is likely to be a brain
      specific nuclear protein, functioning in the process of neuronal differentiation.

PMID- 9526062
TI  - The differential distribution of AMPA-receptor subunits in the tectofugal system
      of the pigeon.
AB  - The tectofugal system of the pigeon was examined for the distribution of several
      glutamate-receptor subunits (AMPA Glu R1, Glu R2/3, Glu R4) and the calcium
      binding protein parvalbumin. With respect to the different antigens, a
      heterogeneous distribution was observed. Within the optic tectum, the Glu R1 like
      immunoreactivity was limited to the layers 2-5, 9, 10, and sparsely in layer 13,
      whereas the antibody to Glu R2/3 stained cell bodies in layers 9, 10, and very
      heavily in layer 13. In the rotundus only the Glu R4 antigen was expressed, while
      within the ectostriatal complex a large number of Glu R2/3 and a smaller
      contingent of Glu R4 positive neurons were stained. Quantitative analysis proved
      significant heterogeneities of these antigens in the mesencephalic as well as the
      diencephalic centre of the tectofugal pathway. The number of Glu R2/3 positive
      neurons undergoes a two-fold increase from the dorsal to the ventral lamina 13 of
      the optic tectum. Alterations in the amount of immunoreactive neurons were also
      observed within the rotundus, since the number of Glu R4 positive cells decreased
      from dorsal to ventral. Morphological differences and their correlation with
      functional specializations in visual information processing are discussed.

PMID- 9526063
TI  - Functional involvement of benzodiazepine receptors in ethanol-induced increases
      of diazepam binding inhibitor (DBI) and its mRNA in the mouse brain.
AB  - We have attempted to clarify the mechanisms for alcohol (EtOH)-induced elevation
      of diazepam binding inhibitor (DBI) mRNA and to investigate whether the increase
      in DBI mRNA is paralleled with that in DBI using EtOH-treated mice and primary
      cultured neurons. Both the DBI content and the expression of DBI mRNA were
      elevated in the cerebral cortex of EtOH-inhaled and -withdrawn mice. Simultaneous
      administration of flunitrazepam (FLN) and Ro15-1788 with EtOH vapor completely
      abolished the EtOH-induced elevation of DBI mRNA. In addition, the exposure of
      the neurons for 3 days significantly elevated the expression of DBI mRNA, which
      was completely inhibited by concomitant exposure of FLN, Ro15-4513 and Ro-15-1788
      with EtOH, while muscimol and bicuculline showed no effects on the EtOH-induced
      increase of DBI mRNA expression. These results indicate that functional
      interaction between EtOH and benzodiazepine (BDZ) receptors is a critical role in
      the increased expression of DBI mRNA.

PMID- 9526064
TI  - Detection of mRNAs and alternatively spliced transcripts of dopamine receptors in
      rat peripheral sensory and sympathetic ganglia.
AB  - The presence of mRNAs for dopamine receptor subtypes and dopamine transporter in
      rat peripheral sensory and sympathetic ganglia was investigated using polymerase
      chain reaction (PCR) and DNA sequencing. Dopamine D1, D2, D3, D5 receptor subtype
      mRNAs and dopamine transporter mRNA were detected in both superior cervical
      sympathetic ganglia (SCG) and dorsal root ganglia (DRG) in the rat; the
      expression of D4 mRNA was only detected in DRG. While two alternatively spliced
      isoforms of D2 were detected in both ganglia, the alternative splicing
      transcripts for D3 and D4 were only found in the DRG. These results are useful in
      further studying the roles of dopamine and the effects of dopaminergic agents in
      the peripheral nervous system.

PMID- 9526065
TI  - Multiple actions of nitric oxide on voltage-dependent Ca2+ channels in mouse
      cerebral cortical neurons.
AB  - We investigated the effects of nitric oxide (NO) on voltage-dependent Ca2+
      channels (VDCCs) by examining [45Ca2+]influx into mouse cerebral cortical
      neurons. S-nitroso-N-acetylpenicillamine (SNAP) induced a dose-dependent increase
      in [45Ca2+]influx, which was completely abolished by hemoglobin, tetrodotoxin and
      dibucaine. The NO-induced [45Ca2+influx was significantly inhibited by verapamil
      and omega-agatoxin VIA (omega-AGX), whereas omega-conotoxin GVIA (omega-CTX) had
      no effects on the NO-induced [45Ca2+]influx. KCl (30 mM) stimulated
      [45Ca2+]influx, and verapamil, omega-CTX and omega-AGX reduced the KCl-induced
      [45Ca2+]influx by about 40, 26 and 34%, respectively, indicating that the neurons
      used here possess L-, N- and P-typed VDCCs. SNAP itself reduced KCl-induced
      [45Ca2+]influx by about 28.5%. In the presence of both KCl and SNAP, omega-CTX
      showed no effects on the influx, while verapamil and omega-AGX significantly
      inhibited the influx and the concomitant presence of verapamil and omega-AGX
      completely abolished the influx. These results indicate that NO induces [45Ca2+]
      influx via the opening of L- and P-typed VDCCs subsequent to neuronal membrane
      depolarization and that NO itself inhibited the function of N-typed VDCC in the
      cerebral cortical neurons.

PMID- 9526066
TI  - Intraplantar injection of dextrorphan, ketamine or memantine attenuates formalin
      induced behaviors.
AB  - The possible prophylactic effects of local injection of NMDA receptor antagonists
      that are currently used in humans was investigated in the present study.
      Intraplantar pretreatment with either 5 mM dextrorphan (DEX), 10 mM memantine
      (MEM) or 10 mM ketamine (KET) significantly attenuated formalin-induced lifting
      and licking behaviors, however flinching behavior was not effected. Control
      experiments indicated that these drug actions could be attributed to local and
      not systemic effects of the antagonists. We hypothesize that these actions result
      from blocking NMDA receptors present on unmyelinated sensory axons in the skin.
      These data suggest that peripheral NMDA receptors contribute to nociceptor
      activation and can be manipulated to reduce pain of peripheral origin. Since DEX,
      MEM and KET are currently used in humans and considered clinically safe, they
      have potential therapeutic value in the treatment of physiologic or pathologic
      pain states which are induced or maintained by peripheral nociceptor activity.
      Topical or local application would avoid the side effects that can accompany
      systemic or intrathecal injection of NMDA antagonists.

PMID- 9526068
TI  - Glutamate receptors in dysplasic cortex: an in situ hybridization and
      immunohistochemistry study in rats with prenatal treatment with
      methylazoxymethanol
AB  - Injection of the antimitotic drug methylazoxymethanol (MAM) in the pregnant rat
      at E14 leads in the offsprings to a severe malformation with microcephaly and
      cortical heterotopiae in the white matter and in the CA1 field of the
      hippocampus. These animals suffer cognitive and epileptic disorders. Since these
      pathologies have been associated with glutamatergic transmission abnormalities,
      we have examined by in situ hybridization and immunohistochemistry the
      distribution and expression levels of several glutamate receptors subunits in
      these rats. Examination of the GluR2 flip and flop, NR1, NR2A and NR2B subunit
      gene transcripts showed a qualitatively similar distribution in both the
      neocortex and hippocampus of MAM and control rats. Quantitative analysis revealed
      an altered proportion of the GluR2 flip and flop subunits in the CA1 region of
      MAM animals as compared to controls. Moreover, a 26% reduction in the expression
      of the NR1 subunit and a 40% increase in the expression of the GluR2 flip subunit
      were noted in cortical heterotopiae, as compared to the adjacent neocortex.
      Immunostaining for GluR2/3, NR1 or NR2 showed, in both MAM and control animals,
      that glutamate receptors were mainly concentrated in the soma and dendrites of
      neocortical and hippocampal pyramidal cells, including in heterotopiae, and in
      the apical dendrites of hippocampal granule cells. Abnormalities in the
      expression of glutamate receptor subtypes in cortical heterotopiae and in the
      hippocampal CA1 region could contribute to functional disorders previously
      reported in MAM animals such as memory impairments and epilepsy. Copyright 1997
      Elsevier Science B.V.

PMID- 9526067
TI  - Repeated administration of cocaine, nicotine and ethanol: effects on
      preprodynorphin, preprotachykinin A and preproenkephalin mRNA expression in the
      dorsal and the ventral striatum of the rat.
AB  - It is established that dopamine (DA) controls the expression of preprodynorphin
      (PPDYN), preprotachykinin A (PPT-A) and preproenkephalin (PPE) mRNAs in striatal
      structures. Since cocaine, nicotine and ethanol enhance extracellular DA
      concentration, we have examined whether their repeated administration produced
      common changes in the expression of these mRNAs. Quantitative in situ
      hybridization histochemistry was performed in rats 2 h after a final challenge
      subsequent to repeated subcutaneous injections (3 X a day) of cocaine (12.5
      mg/kg), nicotine (0.4 mg/kg) for 14 days and ethanol (160 mg/kg) for 7 days. In
      the dorsal striatum, cocaine produced simultaneous PPDYN and PPT-A mRNA increases
      without PPE mRNA change whereas nicotine and ethanol produced no modification.
      After cocaine, PPDYN mRNA was preferentially increased in striatal patch
      compartment. In the nucleus accumbens, the effects were more complex. In cocaine
      treated rats, we measured concomitant increases of PPDYN and PPE mRNA in the
      rostral pole, an isolated induction of PPT-A mRNA signals in the core without any
      change in the two shell subregions: the cone and the ventral shell. In contrast,
      after nicotine and ethanol, the ventral shell was the only accumbal subregion
      which showed a neuropeptide mRNA alteration, nicotine leading to decreased PPDYN
      mRNA and ethanol to increased PPT-A mRNA contents. The neuropeptide regulation
      after chronic treatment with these psychostimulant drugs does not strictly
      conform to a general DA control scheme in the dorsal and the ventral striatum.
      The cocaine effects can be clearly distinguished from those of nicotine and
      ethanol in terms of neuropeptide regulation and striatal subregions affected.

PMID- 9526069
TI  - Ultrastructural circuitry of cardiorespiratory reflexes: there is a monosynaptic
      path between the nucleus of the solitary tract and vagal preganglionic
      motoneurons controlling atrioventricular conduction in the cat.
AB  - We have tested the hypothesis: (1) that presumptive negative dromotropic vagal
      preganglionic neurons in the ventrolateral nucleus ambiguus (NA-VL) can be
      selectively labelled from the heart, by injecting one of two fluorescent tracers
      into the two intracardiac ganglia which independently control sino-atrial (SA)
      rate or atrioventricular (AV) conduction; i.e., the SA and AV ganglia,
      respectively. The NA-VL was examined for the presence of single and/or double
      labelled cells. Over 91% of vagal preganglionic neurons in the NA-VL projecting
      to either intracardiac ganglion did not project to the second ganglion.
      Consequently, we also tested the hypothesis: (2) that there is a monosynaptic
      connection between neurons of the medial, and/or dorsolateral nucleus of the
      solitary tract (NTS), rostral to obex, and negative dromotropic neurons in the NA
      VL. An anterograde tracer was injected into the NTS, and a retrograde tracer into
      the AV ganglion. The anterograde marker was found in both myelinated and
      unmyelinated axons in the NA-VL, as well as in nerve terminals. Axo-somatic and
      axo-dendritic synapses were detected between terminals labelled from the NTS, and
      retrogradely labelled negative dromotropic neurons in the NA-VL. This is the
      first ultrastructural demonstration of a monosynaptic pathway between neurons in
      the NTS and functionally associated (negative dromotropic) cardioinhibitory
      neurons. The data are consistent with the hypothesis that the neuroanatomical
      circuitry mediating the vagal baroreflex control of AV conduction may be composed
      of as few as four neurons in series, although interneurons may also be interposed
      within the NTS.

PMID- 9526070
TI  - A human gene encodes a putative G protein-coupled receptor highly expressed in
      the central nervous system.
AB  - The mammalian bombesin (Bn)-like neuropeptide receptors gastrin-releasing peptide
      receptor (GRP-R) and neuromedin B receptor (NMB-R) transduce a variety of
      physiological signals that regulate secretion, growth, muscle contraction,
      chemotaxis and neuromodulation. We have used reverse transcription-polymerase
      chain reaction (PCR) to isolate a cDNA from human brain mRNA, GPCR/CNS, that
      encodes a putative G protein-coupled receptor (GPCR) based upon the presence of
      the paradigmatic seven heptahelical transmembrane domains in its predicted amino
      acid sequence. Analysis of the deduced protein sequence of GPCR/CNS reveals this
      putative receptor to be 98% identical to the deduced amino acid sequence of a
      recently reported gene product and minimally identical (approximately 23%) to
      both murine GRP-R and human endothelin-B (ET-B) receptor. Our deduced protein
      sequence differs at 12 positions, scattered throughout the open reading frame,
      relative to the original sequence. A 3.7 kb GPCR/CNS mRNA species is expressed in
      vivo in a tissue-specific manner, with highest levels detected in brain and
      spinal cord, lower levels found in testis, placenta and liver, but no detectable
      expression observed in any other tissue. Analysis of GPCR/CNS genomic clones
      reveals that the human gene contains one intron that is about 21 kb in length
      that divides the coding region into two exons and maps to human chromosome 7q31.
      No specific binding is observed with either a newly identified ligand (DTyr6,
      beta Ala11, Phe13, Nle14]Bn-(6-14)) having high affinity for all Bn receptor
      subtypes or Bn after GPCR/CNS is stably expressed in fibroblasts. No elevation in
      inositol trisphosphate is observed after the application of micromolar levels of
      either DPhe6, beta Ala11, Phe13, Nle14]Bn-(6-14) or Bn, a concentration of
      agonist known to activate all four known Bn receptor subtypes. When GPCR/CNS is
      expressed in Xenopus oocytes, no activation of the calcium-dependent chloride
      channel is detected despite the addition of micromolar levels of Bn peptide
      agonists. We conclude that the natural ligand for this receptor is none of the
      known naturally occurring Bn-like peptides and the true agonist for GPCR/CNS
      remains to be elucidated.

PMID- 9526071
TI  - Deleterious actions of chronic ethanol treatment on the glycosylation of rat
      brain clusterin.
AB  - Clusterin is a N-glycosylated sialoglycoprotein present in rat brain cells.
      Clusterin, which elicits aggregation in a wide variety of cells, has been
      suggested to play an important role in synaptic remodeling through its cell
      adhesion property or lipid transport capacity in the brain. Sialic acid residues
      in clusterin may be responsible for its structural conformation, stability and
      functional ability. Maturation of clusterin is governed by the relative actions
      of sialyltransferases and sialidases that are present in brain microsomes, golgi
      bodies, cytosol and plasma membranes. We have earlier reported that chronic
      ethanol treatment in rats has a damaging effect on the hepatic glycosylation
      machinery. Others have reported increased hydrolysis of brain sialoconjugates in
      rats following chronic ethanol administration. Specificity of the effects of
      chronic ethanol treatment in the brain in relation to the glycosylation process,
      is still obscure. Therefore, in this investigation, we have studied the specific
      effects of chronic ethanol treatment on the glycosylation of rat brain clusterin
      and the causes that may lead to any possible defects in the glycosylation
      process. We have determined the effects of chronic ethanol treatment on (i) the
      incorporation of labeled leucine and N-acetylmannosamine into immunoprecipitable
      clusterin in whole brain homogenate, microsomes, golgi, cytosol, plasma membrane
      and synaptosomes, (ii) enzymatic activities of sialyltransferases in golgi and
      synaptosomes, and sialidase in brain cytosol and plasma membranes, and (iii) de
      novo synthetic rate of rat brain cytosolic sialidase. Our results showed that
      chronic ethanol treatment in rats resulted in (1) a decreased sialation index of
      brain clusterin by 47. 2% (p<0.001), 56.7% (p<0.05), 51.7% (p<0.05), 64.8%
      (p<0.001), and 54.5% (p<0.05), respectively, in whole brain homogenate, golgi,
      cytosol, plasma membranes, and synaptosomes; (2) a 46.1% (p<0.05) and 12.5%
      (p<0.05) decreased activities of brain sialyltransferases, respectively, in the
      golgi and the synaptosomal fractions; (3) a 70. 1% (p<0.05) and 42.6% (p<0.05)
      increased activities of sialidases, respectively, in the cytosol and plasma
      membrane fractions; and (4) a 22.2%-64.3% (p<0.001) increased incorporation of
      labeled leucine into brain cytosolic sialidase. Our findings have clearly
      established that long-term ethanol treatment in rats leads to a marked impairment
      in the glycosylation of rat brain clusterin as a result of altered activities of
      brain sialation and desialation enzymes. In particular, the specific increase
      noted in brain sialidase activity was due to concomitant increases in its
      synthetic rate. These defects in the glycosylation of brain clusterin may lead to
      changes in the molecular conformation of clusterin, and thus, may result in its
      structural instability and/or functional impairment.

PMID- 9526072
TI  - Functional and molecular expression of PACAP/VIP receptors in the rat retina.
AB  - Receptor binding sites for pituitary adenylate cyclase activating polypeptide
      (PACAP) and vasoactive intestinal polypeptide (VIP), positively coupled to
      adenylate cyclase, have been previously described in the retina of different
      mammalian species. In the present study, we determined the mRNA expression of
      PACAP/VIP receptor variants in the rat retina and investigated their coupling to
      phospholipase C in addition to adenylate cyclase. The two forms of PACAP, PACAP27
      and PACAP38, induced a dose-dependent (1-100 nM) increase of cAMP and
      [3H]inositol monophosphate levels, whereas VIP stimulated, with lower potency and
      efficacy, cAMP formation only. Reverse transcription-PCR analysis in the rat
      retina detected both type-I (PACAP-R and PACAP-HOP splice variants) and type-II
      (VIP-I and -2) receptor-mRNAs. These data indicate that PACAP and VIP may
      interact with multiple receptor subtypes and activate one (VIP) or two (PACAP)
      signal transduction mechanisms in the rat retina.

PMID- 9526073
TI  - Differential effect of chronic morphine on mRNA encoding adenylyl cyclase
      isoforms: relevance to physiological sequela of tolerance/dependence.
AB  - In opiate naive longitudinal muscle myenteric plexus tissue, facilitation (GS
      mediated) and inhibition (Gi-mediated) of adenylyl cyclase (AC) activity is
      observed in response to low (nM) and high (microM) concentrations of sufentanil,
      respectively. Following chronic in vivo exposure to morphine, previously
      inhibitory concentrations produce excitatory effects. The present study was
      undertaken to explore the potential relevance of AC isoform-specific regulation
      to the qualitative change in opioid responsiveness following chronic morphine.
      Following persistent activation of opiate receptors, levels of AC I mRNA remain
      unchanged but that of AC IV is significantly augmented (approximately 37%, P <
      0.05). AC I and IV are differentially regulated by G alpha i and G beta gamma.
      The former is inhibited by G alpha i and G beta gamma whereas the latter is
      relatively insensitive to G alpha i and is stimulated by G beta gamma. Thus, an
      increase in AC IV mRNA could represent a shift from inhibitory to stimulatory
      opiate receptor-G protein signalling, as has been observed following chronic
      morphine. These results indicate that persistent activation of opiate receptors
      can induce selective changes in the abundance (activity) of AC isoforms. This
      could explain, in part, some of the adaptations that occur following chronic in
      vivo morphine exposure.

PMID- 9526074
TI  - Region-specific effect of testosterone on oxytocin receptor binding in the brain
      of the aged rat.
AB  - We reported previously a significant reduction of oxytocin (OT) receptor binding
      in the brain of 20-month old rats relative to 3-month old ones. The present study
      shows that testosterone treatment of aging rats restores normal adult levels of
      OT receptor binding in the olfactory tubercle and in the hypothalamic
      ventromedial nucleus, but not in the caudate-putamen. These data indicate that
      the reduced plasma testosterone found in 20-month old rats is responsible for the
      loss of OT receptors in the olfactory tubercle and hypothalamic ventromedial
      nucleus, whereas other aging-related mechanisms may account for the decrease of
      OT receptor binding in the caudate-putamen.

PMID- 9526076
TI  - Appearance of glutamate-like immunoreactivity during retinal regeneration in the
      adult newt.
AB  - The appearance of endogenous glutamate during retinal regeneration in the newt
      was examined by immunohistochemistry. Glutamate-like immunoreactivity (Glu-LI)
      first appeared in prospective ganglion cells along the vitreal margin of retinas
      that were about six cells thick, in prospective photoreceptors immediately before
      segregation of retinal plexiform layers and then in prospective bipolar cells
      immediately after the initial appearance of thin plexiform layers. In retinas
      nearing complete regeneration, Muller cells showed immunoreactivity. The
      appearance of glutamatergic phenotypes during retinal regeneration seemed to
      follow the order of cell differentiation [T. Saito, Y. Kaneko, F. Maruo, M.
      Niino, Y. Sakaki, Study of the regenerating newt retina by electrophysiology and
      immunohistochemistry (bipolar- and cone-specific antigen localization), J. Exp.
      Zool. 270 (1994) 491-500]. However, changes in the amount of endogenous glutamate
      during retinal regeneration were more complex. On the one hand, Glu-LI at the
      prospective ganglion cell layer temporarily increased during the initial period
      of segregation of the inner plexiform layer. On the other hand, immunoreactivity
      in the photoreceptor layer declined during segregation of the outer plexiform
      layer. The transient expression of immunoreactivity may represent a function of
      glutamate in events such as cell survival or neurite extension during retinal
      regeneration.

PMID- 9526075
TI  - ARIA is heavily expressed in rat peripheral auditory and vestibular ganglia.
AB  - The ARIA (acetylcholine receptor inducing activity) polypeptide is a member of
      the neuregulin gene family. It was originally purified on the basis of its
      ability to induce skeletal muscle nicotinic acetylcholine receptors (nAChRs).
      ARIA mRNA is expressed in ventral horn motor neurons and brain cholinergic
      neurons. We report here that ARIA mRNA is heavily expressed in the embryonic,
      developing, and adult peripheral auditory and vestibular ganglia, the spiral
      ganglion and Scarpa's ganglion. Neither ganglion is cholinergic, but both express
      mRNAs for nicotinic and muscarinic receptors. The expression of ARIA in these
      ganglia may be related to the regulation of cholinergic receptors or a more
      general role for ARIA in growth and development.

PMID- 9526077
TI  - Differential distribution and regulation of estrogen receptor-alpha and -beta
      mRNA within the female rat brain.
AB  - In the present study, estrogen receptor (ER)alpha and ER beta genes were found to
      be differentially expressed in discrete subregions of the rat amygdaloid complex.
      The amygdala nuclei showing predominant ER alpha mRNA expression included the
      posterolateral cortical nucleus, amygdala hippocampal area, and lateral
      dorsolateral nucleus, whereas the amygdala areas with predominant ER beta mRNA
      expression were the medial anterodorsal and central nuclei. Both ER alpha and ER
      beta mRNAs were highly expressed in the medial posterodorsal nucleus. In addition
      to the discrete anatomical expression patterns, there appeared to be a
      differential regulation by estradiol of the ER alpha and ER beta mRNAs. Two weeks
      of estradiol (170 microgram total) treatment decreased ER alpha mRNA expression
      levels in the arcuate, ventromedial hypothalamus, and posterolateral cortical
      amygdala nucleus, but increased ER beta mRNA in the arcuate. In the medial
      amygdala nuclei, only ER beta mRNA levels were altered (reduced) by estradiol
      treatment. These results suggest that estrogen can modulate behaviors and
      functions mediated by the amygdala and hypothalamus via differentially regulated
      ER subtypes.

PMID- 9526078
TI  - Colocalization of calretinin and calbindin-D28k with oxytocin and vasopressin in
      rat supraoptic nucleus neurons: a quantitative study.
AB  - Recent electrophysiological experiments, in which purified calbindin-D28k
      (calbindin) and calretinin antibodies were diffused into these neurons, showed
      that Ca2+-dependent membrane potentials and firing patterns were profoundly and
      predictably affected by Ca2+-binding proteins (CaBPs). The present study used
      quantitative analyses of a dual-labeling immunofluorescence method to investigate
      the colocalization of the CaBPs, calbindin and calretinin in oxytocin (OT)- and
      (VP)-containing neurons of the supraoptic nucleus. Analyses of tissue
      immunostained with two different dilutions of each CaBP antibody used, revealed
      that 84% and 72% of the OT neurons were positive for calbindin immunoreactivity (
      ir) at the higher and lower antibody concentrations, respectively. 52% and 50% of
      OT neurons were positive for calretinin-ir; thus, many OT neurons express both
      calbindin and calretinin. In contrast, only 25% and 18% of VP neurons showed
      calbindin-ir, and they were virtually devoid of calretinin-ir. These results
      provide evidence that CaBP expression in OT neurons is both greater and more
      diverse than in VP neurons, and are consistent with the hypothesis that Ca2+
      buffering capacity contributes to the control of intrinsic firing patterns.

PMID- 9526079
TI  - Site-specific effects of local pH changes in the substantia nigra pars reticulata
      on flurothyl-induced seizures.
AB  - Local cerebral changes of acid-base balance may interfere with neuronal
      communication. Acidosis enhances and alkalosis suppresses GABAA receptor
      neurotransmission while there are opposite effects on NMDA receptor transmission.
      In this study, we determined site-specific effects of acidified solutions of Na
      HEPES-artificial cerebrospinal fluid infused into the anterior or posterior area
      of the substantia nigra pars reticulata (SNR) in rats. Two levels of pH were
      compared: 6.7 and 7.4. Rats were challenged with flurothyl and the threshold for
      clonic and tonic-clonic seizures was determined. In the anterior SNR, there were
      no differences between the effects of the solution with pH 6.7 and 7.4 on
      flurothyl seizures. In contrast in the posterior SNR, microinfusions with pH 6.7
      had proconvulsant effects. The results suggest that local pH changes may have
      site-specific effects on seizure susceptibility in vivo.

PMID- 9526080
TI  - Domain-specific knowledge systems in the brain the animate-inanimate distinction.
AB  - We claim that the animate and inanimate conceptual categories represent
      evolutionarily adapted domain-specific knowledge systems that are subserved by
      distinct neural mechanisms, thereby allowing for their selective impairment in
      conditions of brain damage. On this view, (some of) the category-specific
      deficits that have recently been reported in the cognitive neuropsychological
      literature - for example, the selective damage or sparing of knowledge about
      animals - are truly categorical effects. Here, we articulate and defend this
      thesis against the dominant, reductionist theory of category-specific deficits,
      which holds that the categorical nature of the deficits is the result of
      selective damage to noncategorically organized visual or functional semantic
      subsystems. On the latter view, the sensory/functional dimension provides the
      fundamental organizing principle of the semantic system. Since, according to the
      latter theory, sensory and functional properties are differentially important in
      determining the meaning of the members of different semantic categories,
      selective damage to the visual or the functional semantic subsystem will result
      in a category-like deficit. A review of the literature and the results of a new
      case of category-specific deficit will show that the domain-specific knowledge
      framework provides a better account of category-specific deficits than the
      sensory/functional dichotomy theory.

PMID- 9526081
TI  - A model of reaching dynamics in primary motor cortex.
AB  - Features of virtually all voluntary movements are represented in the primary
      motor cortex. The movements can be ongoing, imminent, delayed, or imagined. Our
      goal was to investigate the dynamics of movement representation in the motor
      cortex. To do this we trained a fully recurrent neural network to continually
      output the direction and magnitude of movements required to reach randomly
      changing targets. Model neurons developed preferred directions and other
      properties similar to real motor cortical neurons. The key finding is that when
      the target for a reaching movement changes location, the ensemble representation
      of the movement changes nearly monotonically, and the individual neurons
      comprising the representation exhibit strong, nonmonotonic transients. These
      transients serve as internal recurrent signals that force the ensemble
      representation to change more rapidly than if it were limited by the time
      constants of individual neurons. These transients, if they exist, could be
      observed in experiments that require only slight modifications of the standard
      paradigm used to investigate movement representation in the motor cortex.

PMID- 9526082
TI  - Binocular rivalry and motion perception.
AB  - In a series of experiments psychophysical techniques were used to study the
      relation between binocular rivalry and motion perception. An initial series of
      experiments confirmed that motion enhances the predominance of an eye during
      rivalry, although the direction of motion does not matter. The presence of an
      annulus of motion immediately surrounding one eye's rival target greatly enhances
      dominance of that target, but the influence of the annulus progressively
      decreases as the separation between disk and annulus increased. Opponent
      directions of motion in disk and annulus yield greater dominance than when dots
      in the disk and annulus moved in identical directions. In a second experiment
      that two eyes were adapted to orthogonal directions of motion, generating strong,
      distinctively different monocular motion aftereffects (MAEs). Even though the two
      eyes view physically identical random-motion displays following differential
      adaptation, binocular rivalry of the discrepant MAEs can occur. Finally, using a
      stimulus replacement technique to measure detectability of translational and
      rotational motion, it was found that both types of motion were readily detected
      during periods of dominance but went undetected during periods of suppression.
      Taken together, these results bear on the process responsible for rivalry and its
      neural locus relative to the analysis of different types of motion.

PMID- 9526083
TI  - Knowing where things are parahippocampal involvement in encoding object locations
      in virtual large-scale space.
AB  - The involvement of the medial temporal-lobe region in allocentric mapping of the
      environment has been observed in human lesion and functional imaging work.
      Cognitive models of environmental learning ascribe a key role to salient
      landmarks in representing large-scale space. In the present experiments we
      examined the neural substrates of the topographical memory acquisition process
      when environmental landmarks were more specifically identifiable. Using positron
      emission tomography (PET), we measured regional cerebral blood flow changes while
      normal subjects explored and learned in a virtual reality environment. One
      experiment involved an environment containing salient objects and textures that
      could be used to discriminate different rooms. Another experiment involved a
      plain empty environment in which rooms were distinguishable only by their shape.
      Learning in both cases activated a network of bilateral occipital, medial
      parietal, and occipitotemporal regions. The presence of salient objects and
      textures in an environment additionally resulted in increased activity in the
      right parahippocampal gyrus. This region was not activated during exploration of
      the empty environment. These findings suggest that encoding of salient objects
      into a representation of large-scale space is a critical factor in instigating
      parahippocampal involvement in topographical memory formation in humans and
      accords with previous studies implicating parahippocampal areas in the encoding
      of object location.

PMID- 9526084
TI  - Category-specific semantic deficits in focal and widespread brain damage: a
      computational account.
AB  - Category-specific semantic impairments have been explained in terms of
      preferential damage to different types of features (e.g., perceptual vs.
      functional). This account is compatible with cases in which the impairments were
      the result of relatively focal lesions, as in herpes encephalitis. Recently,
      however, there have been reports of category-specific impairments associated with
      Alzheimer's disease, in which there is more widespread, patchy damage. We present
      experiments with a connectionist model that show how "category-specific"
      impairments can arise in cases of both localized and widespread damage; in this
      model, types of features are topographically organized, but specific categories
      are not. These effects mainly depend on differences between categories in the
      distribution of correlated features. The model's predictions about degree of
      impairment on natural kinds and artifacts over the course of semantic
      deterioration are shown to be consistent with existing patient data. The model
      shows how the probabilistic nature of damage in Alzheimer's disease interacts
      with the structure of semantic memory to yield different patterns of impairment
      between patients and categories over time.

PMID- 9526085
TI  - Visuospatial attention shift and motor responses in cerebellar disorders.
AB  - The cerebellum has been implicated in higher cognitive functions including
      learning, memory, and attention as well as its well-known role in motor
      programming. Recent studies have suggested that the cerebellum plays a role in
      shifts of attention. We investigated the contribution of the cerebellum to
      visuospatial attentional ability in a trial-by-trial cueing task involving the
      covert orienting of spatial attention. We recorded event-related evoked
      potentials (ERPs) and reaction times (RTs) in patients with cerebellar
      degenerative disorders affecting mainly the lateral cerebellum and compared them
      to age-matched controls. The RT data demonstrated that both the cerebellar
      patients and control subjects responded to the valid cues faster than to the
      invalid cues for both the central and the peripheral cues. Consistent with the RT
      data, the ERP data showed a comparable generation of attention shift-related
      negativities during the cue-target interval for both the central and the
      peripheral cue experiments. The early negative component of the ERP to the target
      was also comparably modulated in both groups as a function of cue validity,
      suggesting efficient facilitation of sensory pathways by prior allocation of
      spatial attention to the cued place. Conversely, the late negative deflection
      preceding the imperative target stimulus and the late sustained positivity
      following target presentation, which reflect neural activities for response
      preparation and selection, were reduced in the cerebellar group. These findings
      suggest that the lateral cerebellum makes little contribution to visuospatial
      attention shift in either the voluntary or automatic modes and support a role of
      the lateral cerebellum in the neural system required for response preparation and
      selection.

PMID- 9526086
TI  - A computational model of how the basal ganglia produce sequences.
AB  - We propose a systems-level computational model of the basal ganglia based closely
      on known anatomy and physiology. First, we assume that the thalamic targets,
      which relay ascending information to cortical action and planning areas, are
      tonically inhibited by the basal ganglia. Second, we assume that the output stage
      of the basal ganglia, the internal segment of the globus pallidus (Gpi), selects
      a single action from several competing actions via lateral interactions. Third,
      we propose that a form of local working memory exists in the form of reciprocal
      connections between the external globus pallidus (Gpe) and the subthalamic
      nucleus (STN). As a test of the model, the system was trained to learn a sequence
      of states that required the context of previous actions. The striatum, which was
      assumed to represent a conjunction of cortical states, directly selected the
      action in the GP during training. The STN-to-GP connection strengths were
      modified by an associative learning rule and came to encode the sequence after 20
      to 40 iterations through the sequence. Subsequently, the system automatically
      reproduced the sequence when cued to the first action. The behavior of the model
      was found to be sensitive to the ratio of the striatal-nigral learning rate to
      the STN-GP learning rate. Additionally, the degree of striatal inhibition of the
      globus pallidus had a significant influence on both learning and the ability to
      select an action. Low learning rates, which would be hypothesized to reflect low
      levels of dopamine, as in Parkinson's disease, led to slow acquisition of
      contextual information. However, this could be partially offset by modeling a
      lesion of the globus pallidus that resulted in an increase in the gain of the STN
      units. The parameter sensitivity of the model is discussed within the framework
      of existing behavioral and lesion data.

PMID- 9526087
TI  - The effect of pictorial illusion on prehension and perception.
AB  - The present study examined the effect of a size-contrast illusion (Ebbinghaus or
      Titchener Circles Illusion) on visual perception and the visual control of
      grasping movements. Seventeen right-handed participants picked up and, on other
      trials, estimated the size of "poker-chip" disks, which functioned as the target
      circles in a three-dimensional version of the illusion. In the estimation
      condition, subjects indicated how big they thought the target was by separating
      their thumb and forefinger to match the target's size. After initial viewing, no
      visual feedback from the hand or the target was available. Scaling of grip
      aperture was found to be strongly correlated with the physical size of the disks,
      while manual estimations of disk size were biased in the direction of the
      illusion. Evidently, grip aperture is calibrated to the true size of an object,
      even when perception of object size is distorted by a pictorial illusion, a
      result that is consistent with recent suggestions that visually guided prehension
      and visual perception are mediated by separate visual pathways.

PMID- 9526088
TI  - Switching attention without shifting the spotlight object-based attentional
      modulation of brain potentials.
AB  - Although psychophysical evidence for object-based attention has been reported,
      corresponding studies with event-related potentials (ERPs) are scarce. Here
      subjects were presented with perceptual fields containing two superimposed
      objects (transparent surfaces generated by two sets of dots in rigid rotation
      around fixation, each set of a different color and direction of motion) or only
      one object (the same dots but either at rest or all rotating in the same
      direction). Brief (150-msec) rectilinear displacements affected either of the
      sets at random ISIs of 350 to 550 msec. Attention was directed to one set of
      dots, guided by color, in order to discriminate the direction of their
      displacement. Motion-onset ERPs elicited by these displacements were compared for
      attended and unattended dots. When the perceptual field consisted of two objects,
      strong suppression of P1 and N1 was obtained in the ERPs associated with the
      unattended object. No suppression was found with the field containing a single
      object, although an enhanced selection negativity was found in ERPs associated
      with attended dots (selected by color). Since the two objects occupied the same
      region of visual space, the suppression of P1/N1 cannot be explained by the space
      based mechanisms but is consistent with object-based attentional selection at
      early stages of vision. The results highlight the role of perceptual
      organizations in enabling alternative attentional mechanisms.

PMID- 9526089
TI  - Unsaturated fatty acids as endogenous bioregulators.
AB  - Most biological functions of unsaturated fatty acids are due to their ability to
      act as second messengers or modulators of activities of functionally important
      proteins; these functions are not related to oxidative metabolism of unsaturated
      fatty acids. These acids regulate the activity of phospholipases, ion channels,
      ATPases, G-proteins, and protein kinases; they also modulate the phosphoinositide
      and sphingomyelin cycles, the transfer of hormonal information, and gene
      transcription. The great diversity of effects of unsaturated fatty acids and
      their presence at the earliest stages of evolution suggest for these
      bioregulators a system-forming role in the living body.

PMID- 9526091
TI  - Bioactive amides of fatty acids.
AB  - Amides of fatty acids are lipid bioregulators formed from long chain saturated
      and unsaturated fatty acids via amidation by the corresponding amines.
      Ethanolamides of fatty acids are the most well-studied species of this group; an
      alternative pathway for their biosynthesis includes hydrolysis of N-acylated
      phosphatidylethanolamines by phospholipase D. Ethanolamides of fatty acids bind
      to the cannabinoid receptors of the central nervous system (CB1) or peripheral
      tissues (CB2) and can be considered as endogenous ligands of these receptors.
      Their pharmacological properties are similar to that of cannabimimetics. Simple
      amides of fatty acids are also endogenous bioregulators acting like sleep
      inducing (oleamide) or angiogenic factors (erucamide). A new group of
      bioregulators comprise the amides of fatty acids and biologically active amines
      (vanillinamine, dopamine, and serotonin).

PMID- 9526090
TI  - 2-Arachidonoyl-glycerol as an "endocannabinoid": limelight for a formerly
      neglected metabolite.
AB  - Previously believed to simply be an intermediate in tri- and diglyceride
      metabolism or an alternative precursor for arachidonic acid, 2-arachidonoyl
      glycerol has lately attracted renewed interest from lipid biochemists and
      pharmacologists. This is due to the finding of its cannabimimetic activity. In
      the present article recent landmarks that have led to the proposition of a role
      of this monoglyceride as an "endocannabinoid", starting from its newly discovered
      pharmacological properties in both central and peripheral tissues and ending with
      studies on the possible biosynthetic pathways for its formation, are reviewed.
      Also considered are possible interactions with another arachidonic acid-derived
      endogenous cannabinoid, anandamide.

PMID- 9526092
TI  - Effect of lysophosphatidylcholine on transmembrane signal transduction.
AB  - Lysophosphatidylcholine (LPC), 1-acyl-sn-glycero-3-phosphocholine, is well known
      as an intermediate of metabolism of phosphatidylcholine (PC), the main
      phospholipid component in all eukaryotic and many prokaryotic cells. LPC is
      produced as a result of PC hydrolysis by several isoforms of phospholipase A2
      (PLA2) and in the reaction mediated by lecithin-cholesterol acyltransferase that
      transfers the fatty acid residue from PC to cholesterol. LPC is classified as a
      second messengers that is produced by activation of cytosolic hormone-activated
      PLA2. It was shown that LPC inhibits transmembrane signaling via receptors, which
      in their active form are linked to G-proteins. There is a viewpoint that LPC
      abolishes formation of the complex between the receptor and G-protein. The effect
      of LPC on protein kinase C (PKC) activation is considered in this review. It was
      shown that low (less than 20 microM) and high (more than 30 microM)
      concentrations of LPC activated and inhibited PKC, respectively. The mechanism of
      LPC-induced activation of PKC still remains unclear. However, the studies of the
      effect of LPC on signal transduction through the PKC-mediated pathway showed that
      LPC probably plays an auxiliary role. It was suggested that LPC may prolong the
      effect of the direct activators of PKC (such as 1,2-diacylglycerol or phorbol
      esters). The physiological role of the elevation of LPC level in tissues is
      associated with its ability to enhance or even evoke cell proliferation,
      stimulate adhesion and differentiation of lymphoid cells, have mitogenic effect
      on macrophages, activate human T-lymphocytes, initiate monocyte chemotaxis,
      decrease myocardial sensitivity to cholinergic stimulation, impair contractility
      of arterial smooth muscle, and modulate aggregation of platelets.

PMID- 9526093
TI  - Phosphoinositide metabolism and Ca2+ oscillation.
AB  - The main pathways of hydrolysis and synthesis of phosphoinositides, metabolism of
      inositol phosphates and their role in animal and human cells are reviewed.
      Mechanisms of regulation of phospholipase C and other key enzymes of
      phosphoinositide metabolism by hormones and growth factors are discussed. The
      mechanisms of regulation of metabolism and cellular activity by second messengers
      formed during activation of phosphoinositide hydrolysis are considered. Special
      attention is given to the regulation of cytoplasmic Ca2+ level by inositol
      phosphates. The review summarizes data on formation and possible biological role
      of inositol phosphates and phosphoinositides containing phosphate at position 3.
      The role of phosphoinositides in the interaction of cellular membranes with
      proteins of the cytoskeleton is considered.

PMID- 9526094
TI  - The bioregulatory role of platelet-activating factor in intracellular processes
      and cell-cell interactions.
AB  - The role of platelet-activating factor (PAF, a phospholipid compound) in
      regulation of cell functions and cell-cell interactions is reviewed. The
      biological effects of PAF on platelets, neutrophils, basophils, eosinophiles,
      lymphocytes, and endothelial cells are described. Mechanisms of cell activation
      by PAF are discussed. Interactions of PAF with other biological regulators
      (prostaglandins, leukotrienes, NO, tumor necrosis factor, and interleukins) are
      considered.

PMID- 9526095
TI  - Correlation between bioeffector characteristics of sphingolipids and the
      structure of their hydrophobic fragment.
AB  - The effect of the structure of the hydrocarbon sphingoid base chain (length,
      presence of double bonds, and steric configuration of functional groups) and the
      length of the fatty acid residue of a ceramide molecule on the bioregulatory
      activities of sphingoids and ceramides is reviewed. Particular emphasis is placed
      on the role of functional groups (OH- and NH2-) typical of the sphingoid chain.

PMID- 9526096
TI  - Functions of sphingosine in cell proliferation and death.
AB  - Interest in the biological functions of sphingosine, the metabolic product of
      sphingolipids, increased dramatically during the last few years. Sphingosine was
      found to be an exogenous inhibitor of protein kinase C and of many cell functions
      which depend on this enzyme including cell proliferation, differentiation, and
      programmed death. Sphingosine also activates some other protein kinases and
      regulates a variety of enzymes which are involved in the transmission of cell
      signals. Sphingosine mobilizes Ca2+ from intracellular stores and controls the
      specific Ca2(+)-channel. Sphingosine influences the synthesis of DNA and
      interacts with DNA in competition for the binding sites with histones, some
      enzymes, and transcriptional factors. Sphingosine is suggested to be a second
      messenger in the transmission of cell proliferation and apoptosis signals. The
      possible use of sphingosine in combined treatment of various diseases as a
      synergist of many drugs is considered.

PMID- 9526097
TI  - Roles of sphingosine-1-phosphate in cell growth, differentiation, and death.
AB  - Recent evidence suggests that branching pathways of sphingolipid metabolism may
      mediate either apoptotic or mitogenic responses depending on the cell type and
      the nature of the stimulus. While ceramide has been shown to be an important
      regulatory component of apoptosis induced by tumor necrosis factor alpha and the
      Fas ligand, sphingosine-1-phosphate (SPP), a further metabolite of ceramide, has
      been implicated as a second messenger in cellular proliferation and survival
      induced by platelet-derived growth factor, neuronal growth factor, and serum. SPP
      protects cells from apoptosis resulting from elevations of ceramide. Inflammatory
      cytokines stimulate sphingomyelinase, but not ceramidase, leading to accumulation
      of ceramide, whereas growth signals also stimulate ceramidase and sphingosine
      kinase leading to increased SPP levels. We propose that the dynamic balance
      between levels of sphingolipid metabolites, ceramide, and SPP and consequent
      regulation of different members of the mitogen-activated protein kinases (JNK
      versus ERK) family is an important factor that determines whether a cell survives
      or dies.

PMID- 9526098
TI  - The roles of ceramide in the regulation of neuronal growth and development.
AB  - Ceramide can be formed by the activity of two general metabolic pathways, the
      anabolic pathway, in which ceramide is formed by acylation of a sphingoid long
      chain base, and the catabolic pathway, in which ceramide is formed by the
      degradation of either glycosphingolipids or of sphingomyelin (SM). The anabolic
      reactions take place in the early compartments of the secretory pathway (the
      endoplasmic reticulum and the Golgi apparatus) and the catabolic reactions take
      place either in lysosomes or at the plasma membrane. Work from our and other
      laboratories has shown that neuronal growth and development can be regulated by
      manipulating ceramide metabolism. Thus, synthesis of glucosylceramide from
      ceramide is required for axonal growth in cultured hippocampal neurons, but the
      formation of ceramide from SM, by a sphingomyelinase activity, stimulates the
      earliest stages of development in these cells, namely the formation of minor
      neuronal processes and the initial formation of the axon. Thus, ceramide and its
      metabolites play distinct roles in the same neuron, depending on the
      intracellular site of generation of ceramide and on the stage of neuronal
      development.

PMID- 9526099
TI  - Leukotrienes: lipid bioeffectors of inflammatory reactions.
AB  - The leukotrienes arise from oxidative metabolism of arachidonic acid through the
      action of the 5-lipoxygenase enzyme, leading to the unstable allylic epoxide
      leukotriene A4. This intermediate represents the substrate for two different
      specific enzymes, namely leukotriene A4-hydrolase and leukotriene C4-synthase,
      generating LTB4 and cysteinyl leukotrienes, respectively. The name "leukotriene"
      is referring to the cellular source (leukocytes are one of the major sources) as
      well as the conjugated triene that characterizes their structure. LTC4 and LTD4
      are potent contracting agents of smooth muscle in airways and blood vessels; in
      addition, they induce mucus secretion and promote plasmatic exudation with direct
      action on endothelial cells. On the other side, LTB4 is known as a potent
      chemokinetic and chemotactic agent. A number of evidences reported in the
      literature underline the potential role of leukotrienes in the inflammatory
      responses that characterize asthma and other pathological conditions. These
      potent lipid bioeffectors are synthesized during the course of inflammatory
      reactions and their pharmacological modulation is able to significantly attenuate
      the clinical manifestations associated with different inflammatory pathologies.

PMID- 9526100
TI  - Natural eicosanoids in regulation of blood coagulation.
AB  - Metabolites of polyunsaturated fatty acids, primarily arachidonic acid, are
      important physiological regulators of blood coagulation. In contrast to many
      other substances involved in coagulation, eicosanoids affect virtually all links
      of hemostasis; they are responsible for blood vessel wall thromboresistance and
      its acquisition of procoagulant properties in response to various agonists,
      regulate the extent of cell-to-cell interactions, modulate reactions of plasma
      hemostasis and blood fibrinolytic activity, and change hemodynamic parameters.
      Such complex effects of eicosanoids on thrombogenesis suggest that they are
      unique and extremely important biologically active substances that strongly
      determine the balance of anticoagulant and procoagulant factors.

PMID- 9526101
TI  - Influence of sphingolipids on T lymphocyte activation.
AB  - Sphingolipid metabolism in immune cells results in formation of a second lipid
      messenger, e.g., ceramide, sphingosine, ceramide-1-phosphate, and sphingosine-1
      phosphate. They are involved in a common signaling which controls the main stages
      of the lymphocyte development, differentiation, activation, and proliferation in
      response to a mitogenic and antigenic stimuli, and to initiate programmed cell
      death. Both, the sphingomyelin cycle products and inhibitor of ceramide synthase-
      fumonisin B1--have been shown to affect the CD3, CD4, CD8, CD45, and other T
      lymphocyte surface antigen expression, to disrupt lymphocyte subpopulation
      balance, to inhibit DNA synthesis in normal lymphocytes, and to suppress an
      immune response to T-dependent antigens in vivo. The common targets of the
      TCR/CD3-derived and sphingolipid-mediated signaling pathways may provide the
      sphingolipid effect on immune cells.

PMID- 9526102
TI  - The simplest proline-containing peptides PG, GP, PGP, and GPGG: regulatory
      activity and possible sources of biosynthesis.
AB  - Our own data and data from the literature on the regulatory role of the simplest
      proline-containing peptides GP, PG, PGP, GPGG, and cyclic-PG are summarized.
      These peptides are involved in homeostasis of gastric mucosa and the
      anticoagulant and fibrinolytic potential of blood plasma. They also potentiate
      memory consolidation processes in the central nervous system. The most probable
      sources of these peptides are polypeptide precursors of collagen, elastin, and
      enterostatin.

PMID- 9526103
TI  - Endothelin-converting enzyme: its functional aspect.
AB  - The system of endothelin peptides and their structure, biological activity, and
      role in physiological and pathological processes are reviewed with emphasis on
      endothelin-converting enzyme (ECE), which catalyzes the terminal processing of
      endothelin. Molecular specificity, structure, isoforms, physicochemical
      characteristics, substrate preference, and tissue localization characterize this
      enzyme as a novel and highly important metalloendopeptidase. The role of ECE in
      pathological processes and data on inhibitors of the enzyme which can have
      medical implication are summarized.

PMID- 9526104
TI  - Oxygen reduction in chloroplasts and the ascorbate cycle 
AB  - Current views concerning the generation of superoxide radicals and hydrogen
      peroxide in chloroplasts as well as their toxic influences on photosynthesis are
      presented. Systems of H2O2 detoxification including the ascorbate peroxidase
      reactions and the ascorbate regenerating reactions are described. Data concerning
      mechanisms of monodehydroascorbate reduction by the photosynthetic electron
      transport chain are reviewed. The participation of the Mehler-peroxidase reaction
      in building of a proton gradient across the thylakoid membrane and its possible
      input in ATP synthesis and in protection from photoinhibition are analyzed.
      Ascorbate functions in chloroplasts and the need to consider the high
      concentration of ascorbate in chloroplasts when photosynthetic reactions in vivo
      are discussed are briefly reviewed.

PMID- 9526105
TI  - A new alternative non-mevalonate pathway for isoprenoid biosynthesis in
      eubacteria and plants.
AB  - Data concerning the discovery of an alternative non-mevalonate pathway for
      isoprenoid biosynthesis leading to isopentenyl diphosphate formation are
      reviewed. This pathway has been discovered in experiments with several eubacteria
      producing triterpenoids of the hopane series. 13C-labeled acetate, glucose, and
      triose phosphates were used as precursors. The 13C-labeling patterns in
      isoprenoids were studied by 13C-NMR spectrometry. In eubacteria the universal C5
      precursor--isopentenyl diphosphate--did not appear to form via the classical
      acetate/mevalonate pathway, but via a novel glyceraldehyde 3-phosphate/pyruvate
      pathway. It is postulated that the condensation of the C2 unit formed as a result
      of pyruvate decarboxylation with the C3 unit (glyceraldehyde 3-phosphate) and the
      next transposition leads to the formation of the branched C5 precursor-
      isopentenyl diphosphate. In Scenedesmus obliquus not only all plastid isoprenoids
      (carotenoids and prenyl side chains of chlorophylls and plastoquinone-9) were
      formed via this novel pathway, but also the non-plastid cytoplasmic sterols. In
      higher plants the plastid isoprenoids were formed via the glyceraldehyde 3
      phosphate/pyruvate pathway, while the cytoplasmic sterols were formed via the
      acetate/mevalonate pathway.

PMID- 9526106
TI  - Changes in structural organization of the nucleosome fiber during protooncogene
      activation.
AB  - Dynamics of structural changes in the chromatin of rat liver cells were studied
      during activation of the c-myc, c-fos, and c-jun protooncogenes. Nuclei were
      isolated at various stages of gene activation using cycloheximide and chromatin
      was subjected to partial nucleolysis by endogenous Ca2+/Mg2+-DNAse and extracted
      with low magnesium buffer; the nucleosome fragmentation was analyzed. DNA was
      isolated from the soluble chromatin and low-molecular-weight fragments were
      separated by electrophoresis through a composite gel system (3 and 1% agarose).
      This modification of DNA electrophoresis protocol improves the efficiency of
      separation of the low-molecular-weight DNA fragments. Increased protooncogene
      activity is associated with decreased content of DNAse-sensitive soluble
      chromatin. The fractional content of the c-fos gene is increased in the soluble
      chromatin. In control nuclei, endogenous Ca2+/Mg2+-DNAse cleaves mononucleosomes
      containing DNA fragments with variable length. Upon protooncogene activation,
      mono- and oligonucleosomes with elongated DNA fragments are predominantly formed.
      The changes involve about 40% of the nuclear chromatin. The data suggest that
      protooncogene activation is associated with reorganization at the nucleosome
      level of the structural organization of the chromatin.

PMID- 9526107
TI  - Comparative study of respiration kinetics and protein composition of skinned
      fibers from various types of rat muscle.
AB  - The respiration parameters of mitochondria from rat heart muscle and from fast
      twitch and slow-twitch skeletal muscle skinned fibers were comparatively
      analyzed. Electrophoretic patterns of fiber protein composition were also
      compared. It was found that fibers with low affinity of mitochondria for ADP
      (i.e., heart and slow-twitch skeletal muscle soleus) contain a 27.5-kD protein
      that is absent from the fibers that exert high affinity for ADP (i.e., fast
      twitch skeletal muscle gastrocnemius). Partial proteolysis, which increases the
      affinity of mitochondria of the heart and slow-twitch skeletal muscles for ADP,
      results in the disappearance of this protein. The results suggest that this
      protein may be an intracellular factor that controls the permeability of the
      outer mitochondrial membrane for ADP.

PMID- 9526108
TI  - RNA-polymerase, DNA-polymerase, DNA-methyltransferase and sphingomyelinase
      activities in liver nuclei of rats of different Age.
AB  - It has been established that activities of RNA-polymerase, DNA-polymerase, DNA
      methyltransferase, and sphingomyelinase in the liver nuclei isolated from newborn
      (2-day-old) rats are by 18, 25, 27, and 610%, respectively, higher than those in
      mature (6-month-old) rats. It has been also shown that the number of single
      stranded stretches in rat liver nuclear DNA increases with age: it is about 2
      fold higher in mature rats than in newborn rats. Thus, the postnatal period of
      ontogenesis is accompanied by both significant changes in DNA structure and
      decrease in activities of enzymes serving for the most important genetic
      processes in cells of animals.

PMID- 9526109
TI  - Photosynthetic generation of O2 and H2 by photosystem I-deficient chlamydomonas
      mutants 
AB  - A comparative study of aerobic generation of O2 and anaerobic photoproduction of
      H2 in whole cells of a wild-type strain of Chlamydomonas reinhardtii and its
      photosystem I-deficient mutants B4 and F8 found no contribution of photosystem II
      to ferredoxin photoreduction, which is not consistent with data of recent studies
      by Greenbaum et al. (Nature, 1995, 376, 438-441; and Science, 1996, 273, 364-367)
      who reported that they had discovered such a capacity in these mutant strains. In
      the wild-type and mutant strains, action spectra showed that O2 was evolved by
      photosystem II, whereas photoinhibition of chlororespiration and evolution of H2
      depended on the activity of photosystem I. Single-turnover flash measurements of
      H2 evolution showed that the contents of photosystem I in mutant strains amounted
      to 3-35% of that in the wild-type strain. This fraction of photosystem I in
      "leaky" mutants displayed abnormal kinetic features and was highly sensitive to
      photoinhibition.

PMID- 9526110
TI  - Interaction of nucleoside diphosphate kinase with membranes of bleached bovine
      retinal rod outer segments. Effects of pH, salts, and guanine nucleotides.
AB  - Soluble nucleoside diphosphate (NDP) kinase in purified bovine retinal rod outer
      segment (ROS) preparations exhibit equilibrium binding to bleached photoreceptor
      membranes. The binding is under the control of pH and concentration of salts
      (NaCl, KCl, CaCl2, or MgCl2). Acidic pH and low ionic strength favor the membrane
      bound form. It was found that: 1) the membrane-bound NDP kinase is released by
      the presence of low concentrations of guanosine 5;-O-(3-thio)triphosphate
      (GTP[S]), GTP, and other related compounds, whereas adenosine 5;-(beta,gamma
      imino)triphosphate (AdoPP(NH)P) is ineffective under similar conditions; 2) the
      binding of NDP kinase to bleached ROS membranes required the presence ROS G
      protein transducin (Gt); and 3) Gt-depleted ROS membranes were still able to bind
      NDP kinase, whereas its apparent affinity was weak and unaffected by GTP[S].
      These results imply that GTP[S]-dependent interaction of NDP kinase with the
      membranes in the presence of bleached visual pigment rhodopsin is mediated by Gt.
      The possible participation of NDP kinase in extremely rapid photoactivation of Gt
      in in vivo ROS is discussed.

PMID- 9526111
TI  - Effect of calcium on the energy status of rat brain synaptosomes under acidosis.
AB  - Incubation of rat brain synaptosomes at pH 6.0 in Ca2+-containing medium is
      associated with a decrease in the ATP content and the rate of oxygen consumption.
      ATP/ADP ratio decreased from 6.6 +/- 0.24 at pH 7.4 to 3.2 +/- 0.17 at pH 6.0.
      The content of 86Rb+ and [3H]tetraphenylphosphonium measured at pH 7.4 did not
      change after preincubation at pH 6.0, indicating the absence of lesion of
      synaptosomal plasma membranes and intrasynaptosomal mitochondria. Incubation with
      1 mM EGTA in Ca2+-free medium as well as addition of 1 mM ouabain or 10 microM
      ruthenium red prevents the effect of acidosis. Similar results were obtained when
      5 mM pyruvate was used as a mitochondrial substrate instead of glucose. It is
      suggested that acidosis-induced decrease in the ATP level is associated with the
      increase in Ca2+ concentration in the cytoplasm and its transport into
      mitochondria. Ouabain reverses this process due to activation of Na+/Ca2+
      exchange.

PMID- 9526113
TI  - Teichoic acids of the cell wall of Nocardiopsis listeri, Nocardiopsis
      lucentensis, and Nocardiopsis tregalosei.
AB  - The structures of teichoic acids of three Nocardiopsis species were established.
      The cell wall of Nocardiopsis listeri VKM Ac-1881T contains two teichoic acids
      (TA). TA1 is 1,3-poly(glycerol phosphate) with 50% glycerol phosphate residues
      substituted by alpha-N-acetylglucosamine in the C-2 position. TA2 is 1, 5
      poly(ribitol phosphate) with each ribitol phosphate unit carrying pyruvate acetal
      groups in the 2 and 4 positions. The cell wall of Nocardiopsis lucentensis VKM Ac
      1963T contains only one teichoic acid of the same structure as TA1 of N. listeri.
      The teichoic acid of the Nocardiopsis tregalosei VKM Ac-942 is a 1,3
      poly(glycerol phosphate) substituted (60%) by beta-glucopyranosyl residues.
      Structures of polymers were studied by chemical and NMR spectroscopy methods. The
      presented results confirm the species-specificity of teichoic acids from
      Nocardiopsis genus.

PMID- 9526112
TI  - Some natural and synthetic antioxidants as stabilizers of beta-carotene
      conversion into vitamin A.
AB  - The effect of antioxidants (vitamins C and E, quercetin, probucol, butylated
      hydroxytoluene) on the oxidation of beta-carotene and its conversion into retinal
      under the influence of beta-carotene 15,15'- dioxygenase (CDO) from rat
      intestinal mucosa was studied. The activity of CDO decreased in the presence of
      oxidants. Antioxidants protected both the substrate and the enzyme. The extent of
      the protection depended on the antioxidant type. The combined injection of
      antioxidants and beta-carotene to animals completely or partially prevented the
      inhibition of the intestinal CDO which was caused by products of non-enzymatic
      oxidation of beta-carotene. Vitamins C and E, which protected the enzyme-
      substrate complex in vivo and in vitro, were found to be the most efficient
      protectors of beta-carotene conversion into retinal.

PMID- 9526114
TI  - Isolation and initial characterization of the uridine phosphorylase from
      Salmonella typhimurium.
AB  - The structural udp gene encoding uridine phosphorylase (UPase) was cloned from
      the Salmonella typhimurium chromosome and overexpressed in E. coli cells. The S.
      typhimurium UPase was purified to an apparently homogeneous state, and some
      physicochemical characteristics of the enzyme were studied. The molecular weight
      of one subunit of UPase is 27.5 kD, and the optimal pH for its activity is 7.2-
      7.4. The native S. typhimurium UPase consists of six identical subunits, and its
      molecular weight is about 165 kD. According to these parameters, the S.
      typhimurium UPase is similar to the E. coli UPase. However, these enzymes differ
      substantially from one another by the substrate sensitivity and sensitivity to
      polarity of the medium. The S. typhimurium UPase has much higher phosphorylation
      activity toward thymidine, deoxyuridine, and 5;-bromide- or 5;-fluoride
      containing analogs of nucleosides than that of E. coli UPase.

PMID- 9526115
TI  - Fully reversible redox cycling of 2,6-dimethoxy-1,4-benzoquinone induced by
      ascorbate.
AB  - The kinetics of cyclic redox transformation of 2,6-dimethoxy-1, 4-benzoquinone
      (DMOBQ)--the well-known effective anticancer agent--induced by ascorbate (AscH-)
      were studied in phosphate buffer, pH 7.40, at 37 degreesC using the Clark
      electrode and ESR techniques. The process is due to the electron transfer from
      AscH- to quinone (Q): Q + AscH- --> Q*- + Asc.- + H+ (1), followed by semiquinone
      (Q.-) oxidation: Q.- + O2 --> Q + O2.- (2). DMOBQ, taken even at submicromolar
      concentrations, effectively catalyzed AscH- oxidation that manifested itself by
      intensive oxygen consumption and an increase in the steady-state concentration of
      the ascorbyl radical (Asc.-). The rate of oxygen consumption, ROX, was kept
      almost constant for a long time. ROX was found to be proportional to the [Q][AscH
      ] product and not dependent on the concentrations of the individual reagents. The
      rate constant for reaction (1) determined from ROX and [Asc.-] was as much as 380
      +/- 40 and 280 +/- 30 M-1.sec-1, respectively. When DMOBQ was mixed with the
      corresponding hydroquinone, QH2, in oxygen-free buffer, the ESR signal of Q.-
      which formed due to the equilibrium Q + QH2 left and right arrow 2Q.- + 2H+ (3)
      was observed. The equilibrium constant K3 of (2.6 +/- 0.4).10-5 and the change in
      the reduction potential, DeltaE3 = E(Q/Q.-) - E(Q.-/QH2), of -280 mV were
      calculated from the steady-state concentration of Q.- at pH 7.4 and 37 degrees C.
      From combination of DeltaE3 determined in this study with E7(Q/Q.-) reported in
      the literature, a value of +190 mV was calculated for the standard second one
      electron reduction potential E(Q*-/QH2). The latter is lower by 270-230 mV than
      that for all the studied 1, 4-hydroquinones. The very beneficial combination of
      E(Q/Q.-) and E(Q.-/QH2) was suggested to be the basic reason for the perfect work
      of DMOBQ as a redox cycling agent and its pronounced anticancer activity.

PMID- 9526117
TI  - Site-specific endonuclease SscL1 I from strain Staphylococcus species L1.
AB  - A site-specific endonuclease SscL1 I preparation has been isolated and purified
      to near homogeneity from the strain Staphylococcus sp. L1 without admixtures of
      other nuclease activity. DNA cleavage proceeds according to the scheme: 5'-G down
      arrow ANTC-3' 3'-CTNA up arrow G-5', and thus the isolated enzyme is an
      isoschizomer of restriction endonuclease HinfI and belongs to the second class of
      restriction endonucleases. SscL1 I works over a broad range of temperature and
      pH. The enzyme is characterized by high stability during storage.

PMID- 9526116
TI  - Isolation and characterization of site-specific endonuclease Bsp123 I from
      thermophilic strain Bacillus species 123.
AB  - The preparation of site-specific endonuclease Bsp123 I was isolated and purified
      from the thermophilic strain Bacillus species 123. Endonuclease Bsp123 I
      recognizes the sequence CGCG and cleaves it in the middle between nucleotides G
      and C, producing blunt ends. Thus, Bsp123 I is an isoschizomer of FnuDII. The
      maximal activity of the enzyme is displayed at 42 degrees C, pH 8.0, 100 mM NaCl,
      10 mM MgCl2.

PMID- 9526118
TI  - An isocratic, reversed-phase HPLC method for the determination of postischemic
      efflux of purines and pyrimidines during reperfusion of isolated liver.
AB  - An isocratic, reversed-phase HPLC method was developed for the determination of
      the rates of purine and pyrimidine efflux during early reperfusion of isolated
      organs after non-perfusion cold conservation. The method enables determination of
      uric acid, cytidine, xanthine, hypoxanthine, uridine, AMP, inosine, and adenosine
      in liver perfusate using a standard C-18 column (25 cm length). Peaks are
      resolved by elution with buffer containing 1% acetonitrile, 20 mM potassium
      citrate (pH 6.25), and 25-55 mM tetramethylammonium. The effects of pH and
      solvents on peak retention times are described. As an example of the application
      of the method, the effects of allopurinol on the rates of postischemic efflux of
      purines and pyrimidines during reperfusion of liver stored in the cold for 24 h
      in Euro-Collins solution was studied.

PMID- 9526120
TI  - Use of flow cytometry as a tool to study mitochondrial membrane potential in
      isolated, living hepatocytes.
AB  - The present paper describes the possibility of determination of mitochondrial
      membrane potential (Deltapsi) in isolated hepatocytes making use of a Deltapsi
      sensitive dye, i.e., the lipophilic cationic probe 5,5',6,6'-tetrachloro-1,1',3,
      3'-tetraethylbenzimidazolcarbocyanine iodide (JC-1) and of cytofluorimetry. The
      validity of the method was proved by treating hepatocytes with FCCP (decrease of
      Deltapsi) and subsequent addition of 6-ketocholestanol (increase of Deltapsi).
      The results indicate that the proposed method may be used in laboratory practice.

PMID- 9526119
TI  - Comparative structural and immunochemical characterization of recombinant and
      natural cytochrome p450scc (CYPXIAI).
AB  - Optimization of the conditions for heterologous expression of recombinant
      cytochrome P450scc in E. coli provided an expression level of about 420 nmoles of
      cytochrome P450scc per liter of bacterial culture. A new procedure for
      purification of recombinant protein in substrate-bound high-spin and substrate
      free low-spin form is described. Highly purified electrophoretically homogeneous
      recombinant cytochrome P450scc contains 12.3 and 16.7 nmoles heme per mg protein
      for substrate-free and substrate-bound forms, respectively. The recombinant and
      natural cytochrome P450scc from bovine adrenocortical mitochondria were compared
      functionally and immunochemically. The dissociation constants for the complexes
      of cytochrome P450scc with cholesterol and adrenodoxin, the efficiency of
      enzymatic reduction in the reconstituted system (NADPH--adrenodoxin reductase-
      adrenodoxin), and cholesterol side-chain cleavage activity were determined. It
      was found that limited proteolysis of the recombinant cytochrome P450scc with
      trypsin forms two main fragments which are electrophoretically and
      immunochemically identical with the fragments F1 (29.8 kD) and F2 (26.6 kD)
      formed during proteolysis of bovine adrenocortical cytochrome P450scc. The
      quantitative values of the studied parameters are practically identical in
      natural and substrate-bound recombinant cytochrome P450scc, while there were
      great differences between substrate-bound and substrate-free forms of recombinant
      cytochrome P450scc both of functional (decrease of cholesterol side-chain
      cleavage activity, efficiency of enzymatic reduction in the reconstituted system,
      and affinity to adrenodoxin for substrate-free cytochrome P450scc) as well as
      structural (increase in accessibility to exogenous and endogenous proteolysis)
      character. The identity of the folding process for recombinant and natural
      proteins as well as the nature of a stabilizing and activating effect of
      cholesterol on cytochrome P450scc is discussed.

PMID- 9526121
TI  - Knowledge-based potentials--back to the roots.
AB  - Applications of knowledge-based quantities in protein structure theory are well
      established but their theoretical foundation, physical interpretation, and range
      of applicability seems unclear or even controversial. Moreover, the current
      literature contains terms like "pseudo-energy", "energy-like quantity", or "true
      energy" which are vague and unclear and terms like "mean-force potential"
      corresponding to well defined concepts. Seemingly contradictory results are often
      caused by inconsistent terminology. Often such problems are resolved when the
      physical nature of the involved quantities is properly defined. We summarize the
      fundamental principles of mean-force potentials and radial distribution functions
      as defined in statistical mechanics and put these into perspective with the term
      "knowledge-based potential".

PMID- 9526122
TI  - The role of active site flexibility in enzyme catalysis.
AB  - It has been shown in this and other laboratories that during the unfolding of a
      number of enzymes inactivation generally precedes global unfolding of the enzyme
      molecule, leading to the suggestion that enzyme active sites are usually more
      "fragile" and more easily "perturbed" than the molecule as a whole and are
      therefore conformationally more flexible than the rest of the molecule. However,
      the role of active site flexibility in enzyme catalysis still remains to be
      explored. In the induced fit hypothesis originally proposed by Koshland, the
      presence of the substrate induces a conformational change at the active site so
      as to fit with the structure of the substrate. By X-ray crystallographic
      structural analysis of E. coli dihydrofolate reductase liganded with cofactors
      and substrates, Sawaya and Kraut showed the enzyme in different conformational
      states indeed while complexed with different ligands, suggesting that the enzyme
      molecule passes through different conformational states through the whole process
      of catalysis. Muscle lactate dehydrogenase can be stabilized either in
      concentrated ammonium sulfate or by cross-linking with glutaraldehyde together
      with a decrease in enzyme activity which can be restored to the original level in
      dilute guanidine hydrochloride possibly by increased flexibility at the active
      site. It is known that a number of enzymes can be activated by chaotropic agents
      such as urea or guanidine hydrochloride. The activation of dihydrofolate
      reductase by either urea or guanidine hydrochloride is accompanied by an increase
      in susceptibility to proteolysis. Isolation of the tryptic peptides of the
      activated enzyme and sequence analysis allowed identification of the sites of
      proteolysis to be at or near the active site of the enzyme, indicating an opening
      up of the active site conformation in the activated state. All the above indicate
      that active site flexibility plays an important role in enzyme catalysis. It is
      possible that during the catalytic cycle, the enzyme molecule passes through
      different stages and each stage requires the molecule to be in a different
      conformation, especially at the active site. Rapid transition between the
      different conformational states, and hence the flexibility of the active site, is
      therefore mandatory for the maximal expression of enzyme activity.

PMID- 9526124
TI  - The use of fluorescence methods to monitor unfolding transitions in proteins.
AB  - The advantages and some limitations of the use of fluorescence methods for the
      quantitative determination of the thermodynamics of protein unfolding transitions
      (i.e., induced by temperature or chemical denaturant) are discussed. Advantages
      include the sensitivity, multi-dimensional nature of the data, wide amenable
      concentration range, high signal-to-noise, rapidity of measurement, and
      adaptability to a variety of sample compartments. Aside from the need for a
      probe, some problems associated with the method involve the handling of baselines
      for the pre- and post-transition regions and the difficulty (shared by most other
      methods) of discerning whether the transition is two-state or multi-state.

PMID- 9526123
TI  - Denatured states of yeast phosphoglycerate kinase.
AB  - Structures of proteins in unfolded states have important implications for the
      protein folding problem and for the translocation of polypeptide chains. Acid
      denatured, cold-denatured, and 6 M guanidine hydrochloride (GuHCl) denatured
      yeast phosphoglycerate kinase (PGK) are ensembles of flexible unfolded molecules
      with rapidly interconverting structures of the individual polypeptide chains.
      They differ, however, in their physical properties, such as in coil size and in
      stiffness over a short distance along the chain. These properties of polypeptide
      chains can be described well by persistence statistics. A solution containing 0.7
      M GuHCl at 4.5 degrees C is nearly a Theta-solvent for PGK. By contrast, 6 M
      GuHCl is a good solvent for PGK. Acid-denatured PGK at low ionic strength has the
      most expanded and stiffest chains. The conformation of heat-denatured PGK should
      be more compact than that of random walk chains at the Theta-point, as can be
      inferred from measurements on other proteins. Investigations of heat-denatured
      PGK by scattering methods are unfeasible due to aggregation of the protein. The
      persistence length as a measure of chain stiffness varies between a = 1.74 nm for
      cold-denatured PGK and a = 3.0 nm for acid-denatured PGK. The distribution
      functions of the gyration radii were calculated from the X-ray scattering data
      for all unfolded states and compared with the radius of gyration of the natively
      folded molecule.

PMID- 9526125
TI  - Local structure and dynamics in proteins characterized by hydrogen exchange and
      mass spectrometry.
AB  - Amide hydrogen exchange rates, determined by NMR spectroscopy, have become an
      important tool that is often used to investigate structure and dynamics of small
      proteins. Recent developments in mass spectrometry and sample handling methods
      make possible measurement of deuterium levels at peptide amide linkages in
      polypeptides. The ability to make these measurements has led to development of
      the protein fragmentation/mass spectrometry approach for determining amide
      hydrogen exchange rates in short segments of intact proteins following their
      incubation in D2O. Partially deuterated proteins are proteolytically fragmented
      into peptides whose molecular weights are determined by on-line liquid
      chromatography/mass spectrometry. Deuterium levels, which are determined from the
      molecular weights of the peptic fragments, can be used to determine amide
      hydrogen exchange rates. Details of the protein fragmentation/mass spectrometry
      approach, along with a brief review of the theory of amide hydrogen exchange, are
      described. The ability to detect and locate minor structural differences in
      proteins by the protein fragmentation/mass spectrometry approach is illustrated
      using oxidized and reduced cytochrome c. These results show that oxidation of
      iron has little effect on the N- and C-terminal regions, but significantly
      destabilizes the interior regions of cytochrome c. The ability to detect
      localized unfolding in large proteins is illustrated with aldolase that was
      equilibrated in acid. Despite the success achieved by NMR spectroscopy for
      determining amide hydrogen exchange rates, mass spectrometry is advantageous
      because it permits studies of large proteins, requires only picomoles of protein,
      and provides a direct measure of structural heterogeneity.

PMID- 9526126
TI  - Stability and co-operative properties of partially folded proteins.
AB  - Biophysical and thermodynamic properties of various partially folded forms of
      proteins are considered which can be obtained by (a) removal of prosthetic
      groups, (b) acid denaturation, (c) melting of subdomain-containing proteins, and
      (d) selective cleavage of disulfides. The examples of alpha-lactalbumin and
      myoglobin will be discussed in more detail. The existence of both co-operative
      and gradual transitions is shown. The results do not support the idea that the
      molten globule represents a distinct thermodynamic state.

PMID- 9526127
TI  - Dissociative thermal inactivation, stability, and activity of oligomeric enzymes.
AB  - Results of kinetic studies on dissociative thermal inactivation of oligomeric
      enzymes are discussed. Dissociative thermal inactivation is the process in which
      the kinetically irreversible protein change is preceded by a reversible stage of
      oligomer dissociation. In experiments, this is demonstrated by the dependence of
      inactivation rate on total protein concentration. This paper gives the relations
      which allow the calculation from experimental data the following physicochemical
      constants which characterize the stability of oligomeric enzymes: the constant
      for the rate of irreversible change of monomeric protein, the equilibrium
      constant for dimer dissociation, and the rate constant for dimer dissociation.
      The problem of a "conformational lock", the contact between protein globules that
      admits a multistep destruction of active oligomer and explains the induction
      period occurring in kinetic thermal inactivation curves, is discussed. The X-ray
      structural analyses for several dimeric enzymes, i.e., alkaline phosphatase (EC
      3.1.3.1) from E. coli, alcohol dehydrogenase (EC 1.1.1.1) from horse liver, and
      baker's yeast enolase (EC 4.2.1.11), explain why they lose catalytic activity
      during the dissociation of the protein into monomers and also provide a
      physically reasonable picture of the structure of their conformational lock.
      Also, these data support the kinetic scheme used to describe the dissociative
      inactivation of dimeric enzymes.

PMID- 9526128
TI  - What ultrastable globular proteins teach us about protein stabilization.
AB  - Proteins, due to their delicate balance of stabilizing and destabilizing
      interactions, are only marginally stable if physiological conditions are
      considered as the standard state. Enhanced intrinsic stability of "ultrastable"
      proteins, e.g., from extremophiles, requires only minute local structural
      changes. Thus, general strategies of stabilization are not available for
      temperature, pH, salt, or pressure adaptation. Mechanisms of enhanced thermal
      stability involve improved packing or docking of structural elements (domains,
      subunits), as well as specific local interactions, e.g., networks of ion pairs.
      Relating the structure and stability of eye lens crystallins (which do not
      undergo any turnover during the life time of an organism), point mutations,
      nicking and swapping of domains, grafting of linker peptides between domains, and
      denaturation-renaturation allowed the cumulative nature of protein stability and
      its relation to the hierarchy of protein structure and folding to be established.
      In this review, recent results for crystallins and enzymes from hyperthermophiles
      will be discussed as models to illustrate mechanisms of protein stabilization.

PMID- 9526129
TI  - Differential scanning calorimetric studies on myosin and actin.
AB  - This review is concerned with the application of the method of differential
      scanning calorimetry (DSC) to structural and functional studies of myosin and
      actin--the main two proteins of muscles and many other systems of biological
      motility. The domain organization of these proteins as revealed by DSC is
      considered. Data are presented on the conformational changes which occur in the
      myosin head and in F-actin due to the formation of the ternary complexes with ADP
      and Pi analogs (such as orthovanadate, beryllium fluoride, or aluminum fluoride).
      Recent data on the application of DSC to studies on the interaction of F-actin
      with myosin heads and with tropomyosin are also considered. It is concluded that
      DSC offers a new and promising approach to probe the structural changes which
      occur in the myosin head and in F-actin during ATP hydrolysis and due to
      interaction of these proteins with each other.

PMID- 9526130
TI  - Chemical modification and chemical cross-linking for protein/enzyme
      stabilization.
AB  - The protein function as well as its stability is governed by the amino acid
      sequence which in turn defines the collective noncovalent interactions leading to
      its specific conformation. Hence, it is not surprising that chemical modification
      with monofunctional and bifunctional reagents (the latter is called chemical
      cross-linking) causes structural changes (sometimes even subtle) which can result
      in significant changes in the stability. This review, while recapitulating the
      early lessons, analyses recent work (including work from authors' laboratory)
      involving these twin approaches for protein stabilization. In the case of
      chemical modification, both surface hydrophilization and enhancing surface
      hydrophobicity are reported to have enhanced protein stability in different
      cases. For cross-linking, the nature, span, and position of the cross-link are
      important factors in the stabilization achieved. It is also pointed out that in
      the case of aqueous-organic cosolvent mixtures, protein stability may depend upon
      the nature of the organic solvents. In the case of polyphenol oxidase and trypsin
      (at least), it is possible to choose "good" solvents on the basis of the Polarity
      index of the solvent.

PMID- 9526131
TI  - Enzyme stability in systems with organic solvents.
AB  - This review deals with enzyme stability in organic solvent systems. Based on the
      current state of the problem, catalytic activity is chosen as the main tool for
      testing enzyme stability. Various enzyme properties being regarded as their
      "stability" at present, a classification of the types of enzyme stability most
      often discussed in the literature is put forward. Aggregation state of the
      biocatalytic system formed a basis for the analysis of enzyme stability in
      organic solvent systems. Regularities of enzyme function in homogeneous solutions
      in water--organic co-solvent mixtures and suspensions in practically anhydrous
      solvents are discussed, kinetic data being analyzed in parallel to results of
      structural studies. Based on the elaborated regularities, up-to-date methods for
      enzyme stabilization in organic solvent systems are considered.

PMID- 9526132
TI  - Deterioration of lyophilized pharmaceutical proteins.
AB  - The successful use of proteins in pharmaceutical and other commercial
      applications requires close examination of their relative fragility. Because of
      the resultant enhanced stability, proteins are often formulated in the solid
      state, even though dehydration tends to alter their structure. Even in the solid
      form, however, proteins may become inactivated due to various deleterious
      processes, e.g., aggregation. This review focuses on such mechanisms, with an
      emphasis on case studies conducted in our laboratory. Proteins which have both
      disulfide bonds and free thiols may aggregate via thiol-disulfide exchange, and
      this process may be facilitated by lyophilization-induced structural
      perturbations. For proteins possessing disulfides but not free thiols,
      aggregation also may occur when native disulfides are beta-eliminated, thus
      giving rise to thiol species which can catalyze disulfide scrambling. Other
      deleterious processes have also been uncovered, including a formaldehyde-mediated
      aggregation of formalinized vaccines. It is illustrated how knowledge of such
      deterioration pathways makes possible the rational development of stable solid
      protein formulations.

PMID- 9526133
TI  - Kinetics of heat aggregation of proteins.
AB  - The mechanism of heat aggregation of proteins proposed by the author involves the
      stage of irreversible denaturation, the stage of nucleation, and the stage of
      growth of aggregates. It was shown that the initial parts of the kinetic curves
      of aggregation followed by monitoring the increase in absorbance (A) or intensity
      of light scattering (I) are linearized in coordinates (dA/dt; t) and (A; t2) (or,
      respectively, in coordinates (dI/dt; t) and (I; t2)). The slope of these linear
      anamorphoses is proportional to the product of the rate constant of irreversible
      denaturation and the rate constant of growth of aggregates. The mechanism of heat
      aggregation proposed is fulfilled for pig heart citrate synthase. The dI/dt
      versus t curves for heat aggregation of glycogen phosphorylase b from rabbit
      skeletal muscles display a lag period whose appearance is caused by
      intramolecular predenaturational changes in the enzyme molecule.

PMID- 9526134
TI  - Induction of (pre) gastrulation and/or (pre) neurulation by subgerminal ooplasm
      and Rauber's sickle in cultured anti-sickle regions of avian unincubated
      blastoderms.
AB  - Rauber's sickle fragments from unincubated quail blastoderms, associated or not
      with chicken central subgerminal ooplasm, were placed on the deep side of the
      upper layer (UL) of the isolated anti-sickle region of unincubated chicken
      blastoderms and cultured in vitro. When only a Rauber's sickle fragment was
      placed, we observed always a pronounced thickening of the UL (pregastrulation) in
      the immediate neighbourhood. Some times a primitive streak (PS) developed. When
      the Rauber's sickle fragment was "sandwiched" between the UL and a central
      subgerminal ooplasmic mass [containing the nucleus of Pander (1817)], always a
      (pre)neural plate accompanied by endophyll developed, not or well associated with
      a primitive streak. In the latter case a complete miniature embryo developed. De
      novo formation of endophyll was observed. As it contained quail nuclei it was
      derived from Rauber's sickle cells which colonized the subgerminal ooplasm. Our
      experiments indicate that the uncommitted upper layer (UL) of the anti-sickle of
      unincubated blastoderms constitutes an excellent reactor tissue for inductions.
      The thickening induced in the UL of the anti-sickle region by Rauber's sickle
      initiates (pre)gastrulation and the thickening induced by endophyll initiates
      (pre)neurulation. In the beginning, pregastrulation and preneurulation seem to be
      independent phenomena. It is only later, when both become correctly linked at the
      right place and time, that a normal embryo will develop.

PMID- 9526135
TI  - Histomorphometric analysis in the ovary of newly hatched chicks treated with
      follicle-stimulating hormone during embryonic development.
AB  - We studied the histomorphometric changes induced in the left ovary of newly
      hatched chicks treated with follicle stimulating hormone (FSH) during embryonic
      development. After FSH treatment the thickness of the ovarian cortex, the number
      per unit of area and total mass per ovary of germ and pregranulosa cells
      increased, accompanied by hypertrophy of the pregranulosa cells. The volume of
      interstitial cell cords, lacunar system, and blood capillaries was increased and
      modifications in poorly differentiated cells were also observed. The number of
      interstitial cells and the average volume of interstitial cells also increased,
      from which we can deduce that these two last events are important in the
      enlargement of the interstitial cell cords. These findings suggest that the
      prefollicular ovary is able to respond to FSH, inducing structural changes both
      in the ovarian cortex as well as in the subcortical medulla.

PMID- 9526136
TI  - Biomechanical significance of cross-sectional geometry of avian long bones.
AB  - Cortical area, maximum second moment of area and polar moment were calculated for
      the long bones of 39 species of birds. Regressions of all these parameters to
      body mass were established. At the same time, the orientations of the maximum
      second moment of area were statistically tested. The parameters calculated on
      humerus and ulna scaled according to the predictions derived from the geometric
      similarity hypothesis, while those calculated for the long bones of the leg
      showed higher exponents, very close to the predictions of the elastic similarity
      hypothesis. Confidence intervals calculated for radius parameters appeared to
      agree with both predictions. Only the for tarsometarsus was it impossible to
      establish a global orientation pattern for the maximum second moment of area. In
      the other cases, the orientation was: sagittal in the radius, posteromedial
      anterolateral in the proximal long bones (humerus and femur) and posterolateral
      anteromedial in the distal long bones (ulna and tibiotarsus). The implications of
      the present findings are discussed in terms of the possible correlations between
      the orientation patterns produced in the cross-sectional geometry of avian long
      bones and the load carried.

PMID- 9526137
TI  - Poll glands of the one-humped camel (Camelus dromedarius): a histochemical and
      scanning electron microscopic study.
AB  - Poll glands of the one-humped camel were obtained to examine their secretory
      mechanism by lectin histochemistry, immunohistochemistry and scanning electron
      microscopy. The glands were composed of numerous conical lobules which consisted
      of apocrine tubules. Lectins of peanut agglutinin (PNA), Dolicos biflorus
      agglutinin (DBA) and wheat germ agglutinin (WGA) showed a variety of staining in
      the Golgi areas and secretory granules in secretory cells of the apocrine
      tubules. Most myoepithelial cells stained intensely with a-smooth muscle actin.
      Varicose nerve fibers immunostained with protein gene product 9.5 were scattered
      among apocrine tubules. Scanning electron microscopy revealed that the luminal
      surface of secretory cells was covered with microvilli and that secretory cells
      pinched off smooth-surfaced apocrine blebs. After pinching off, crater-like pits
      remained on the luminal surface of secretory cells. These findings are similar to
      those obtained from the infraorbital glands of the serows.

PMID- 9526138
TI  - Types and sub-types of neurons in dorsal root ganglia of the lizard Podarcis
      sicula: a light and electron microscope study.
AB  - A morphological analysis of types and sub-types of neurons from dorsal root
      ganglia at different spinal levels was carried out by combined light and electron
      microscopy in Podarcis sicula. Two neuron types were recognized: small dark cells
      (type D) and large light cells (type L). Type L cells were further sub-divided
      into three sub-types (L1, L2, L3) on the basis of entity and distribution of
      neurofilaments. Percentage distribution of neuron types did not vary in relation
      to the spinal level. On the contrary, differences were found in the percentage of
      the three type L neuron sub-types; a higher percentage of cells very rich in
      neurofilaments (L2, L3) was found in dorsal root ganglia from the cervical and
      the lumbar spinal levels. Results are discussed in relation to the spinal-level
      related extent of innervation territory of dorsal root ganglia.

PMID- 9526139
TI  - Expression of the carbohydrate antigen CD15 in rat uterine epithelial cells
      during the early stages of pregnancy.
AB  - The presence and distribution of the carbohydrate antigen CD15 in rat uterine
      epithelial cells was determined using immunohistochemical localisation at both
      light and electron microscopical levels. Rat uterine tissue was examined on days
      1, 3 and 6 of pregnancy and it was found that expression of CD15 was highly stage
      specific with negligible detection on days 1 or 3 of pregnancy but very strong
      expression at both light and electron microscopic levels on day 6. Electron
      microscopy using ferritin as marker revealed expression in the glycocalyx of the
      plasma membrane of uterine epithelial cells. This strongly stage-specific
      expression of CD15 and the extracellular surface localisation suggests an
      important role for this antigen during the early stages of pregnancy in the rat
      and implicates the molecule in attachment to the uterine epithelium.

PMID- 9526140
TI  - Three-dimensional development of bovine reticular cell (Cellula reticuli).
AB  - This paper describes the three-dimensional construction of the reticular cell,
      cellula reticuli, in bovine reticulum and its ontogenetic development. Reticular
      cells of fetal suckling calf and adult tissues were investigated both at the
      surface of intact mucosa and macerated samples using scanning electron
      microscopy. At the third month of gestation, the formation of the reticular cells
      on the mucosal surface started from the center of the cell and just above the
      reticular crest. The reticular crests were observed on the surface of the
      macerated sample at an earlier period of gestation (third month). In the eighth
      month of gestation, primary, secondary and tertiary reticular crests and papillae
      could be observed from the mucosal surface. Macerated samples showed that those
      structures were already formed completely under the epithelium by the first half
      of the seventh month of gestation. It is suggested that the development of the
      reticular papillae starts from the lower to the upper parts of the reticular
      cell.

PMID- 9526141
TI  - Establishing morphine and U-50,488H as discriminative stimuli in a three-choice
      assay with pigeons.
AB  - Pigeons were trained in a 3-choice assay to discriminate among injections of 5.6
      mg/kg U-50,488H, 5.6 mg/kg morphine, and vehicle solution. In dose-response
      tests, subjects rarely responded on the U-50,488H-appropriate key when morphine
      was administered or on the morphine-appropriate key when they received U-50,488H.
      A high dose of naltrexone (1.0 mg/kg) completely blocked the morphine cue but
      failed to block completely the U-50,488H cue. In generalization tests, d
      amphetamine primarily engendered saline-appropriate responding. Ethylketazocine
      produced mixed results, in that moderate doses produced responding on both the
      morphine- and U-50,488H-appropriate keys, but 3.2 mg/kg engendered primarily
      morphine-appropriate responding. These results demonstrate the feasibility, but
      not necessarily the value, of 3-choice discrimination procedures involving mu and
      kappa agonists and vehicle.

PMID- 9526142
TI  - Delta-opioid stimulation by BW373U86 promotes autonomic reactivity to stressors
      and alters attention-related cardiac responses in rabbits.
AB  - The nonpeptide delta-opioid agonist BW373U86 (3 to 300 micrograms/kg) was tested
      in rabbits for effects on heart rate, cardiac orienting and Pavlovian conditioned
      responses to tones, and unconditioned cardiac and somatomotor responses to
      signaled and unsignaled shocks. BW373U86 did not alter shock-evoked somatomotor
      reflexes and had few effects on the development or retention of Pavlovian
      conditioned heart rate discrimination. However, BW373U86 appeared to modulate
      cardiac conditioning indirectly, by facilitating sympathetic reflexes evoked by
      the signaled stressor, and the dose effect was U-shaped within the dose range
      tested. The pronounced tachycardiac effect of BW373U86 was completely blocked, or
      rapidly reversed, by the selective delta-opiate antagonist naltrindole. BW373U86
      was more potent in increasing signaled than unsignaled shock-evoked tachycardia,
      suggesting release of an endogenous substance (e.g., a delta-opioid) because of
      the Pavlovian conditioning contingency.

PMID- 9526143
TI  - A novel paradigm to investigate regulation of drug intake in rats self
      administering cocaine or heroin intravenously.
AB  - The purpose of this experiment was to investigate the regulation of drug intake
      in rats (n = 20) self-administering heroin or cocaine during daily 5-hr sessions.
      Operant chambers were equipped with 2 levers and associated stimulus lights. A
      response on the lever with stimuli signaling an increase in dose size increased
      the infusion duration by 3 s, and a response on the lever with stimuli signaling
      a decrease in dose size decreased the infusion duration by 3 s. Results showed
      that daily and hourly drug intake for cocaine and heroin groups were relatively
      constant. Significant correlation coefficients were obtained for heroin and
      cocaine groups for the relationship between interdose interval (IDI) and infusion
      duration (dose size). These findings indicate that subjects regulated their drug
      intake by adjusting IDI throughout drug self-administration sessions.

PMID- 9526144
TI  - Discriminative-stimulus and participant-rated effects of methylphenidate,
      bupropion, and triazolam in d-amphetamine-trained humans.
AB  - The discriminative-stimulus and participate-rated effects of a range of doses of
      d-amphetamine (2.5-20 mg), methylphenidate (5-40 mg), bupropion (50-400 mg), and
      triazolam (0.0625-0.5 mg) were tested in 5 humans trained to discriminate between
      oral d-amphetamine (20 mg) and placebo. d-Amphetamine and methylphenidate
      generally dose dependently increased drug-appropriate responding. Bupropion and
      triazolam on average occasioned less than or equal to 40% drug-appropriate
      responding. d-Amphetamine, methylphenidate, and bupropion produced stimulant-like
      participant-rated effects, while triazolam produced sedative-like effects. These
      results further demonstrate that the acute behavioral effects of d-amphetamine
      and methylphenidate overlap extensively in humans, which is concordant with
      preclinical studies. Bupropion produced some d-amphetamine-like, participant
      rated drug effects but did not occasion significant levels of d-amphetamine
      appropriate responding. These findings are concordant with previous findings of a
      dissociation between the discriminative-stimulus and participant-rated effects of
      drugs.

PMID- 9526145
TI  - Reactivity to instructed smoking availability and environmental cues: evidence
      with urge and reaction time.
AB  - Reactivity to drug-related cues has been proposed as a possible mechanism to
      explain maintenance of drug use and relapse. This study examined whether
      cognitions associated with drug use (the belief that nicotine is available for
      use) also elicit reactivity. Smokers (N = 132) were randomly assigned in a 2
      (Smoking Availability) x 2 (Smoking Stimuli) factorial design. Reactivity was
      measured by self-reported urge and probe reaction time. A main effect for
      availability was found in that participants who had been told that they could
      smoke shortly reported greater urges than those who had been told that smoking
      would not be permitted for 3 hr. Moreover, smoking-related stimuli produced
      increases in urge ratings only when participants had been told that smoking would
      be available shortly. Probe reaction time, in contrast, increased in the presence
      of smoking stimuli only when participants were told that cigarettes were
      unavailable. The theoretical and treatment implications of drug availability as a
      moderator of cue reactivity, as well as the utility of reaction time as an index
      if drug use motivation, are discussed.

PMID- 9526147
TI  - Expectancy challenge and drinking reduction: process and structure in the alcohol
      expectancy network.
AB  - Expectancies' mediational (control) role in alcohol consumption has been
      supported by both correlational and experimental evidence (J. Darkes & M. S.
      Goldman, 1993; M. S. Goldman, P. E. Greenbaum, & J. Darkes, 1997; L. Roehrich &
      M. S. Goldman, 1995). This study assigned participants (n = 54) to 1 of 2
      expectancy challenges targeting the expectancy dimensions of either arousal or
      sociability identified by B. C. Rather and M. S. Goldman (1994), or to a no
      treatment control, to examine the relationship of the structure and process of
      change in alcohol expectancies. Both challenges resulted in reduced consumption
      and expectancies immediately posttreatment and 6 weeks later after a short
      "booster" session. These results may reflect the lack of "discrete" expectancy
      structure and provide further support for the exploration of these methods as a
      possible prevention strategy.

PMID- 9526146
TI  - Parkinsonian patients report blunted subjective effects of methylphenidate.
AB  - Mesolimbic-mesocortical dopamine brain circuits important for psychostimulant
      reward in animals are developed to greater extents in humans. Brains of patients
      with Parkinson's disease show depletion of ventral tegmental area mesolimbic
      mesocortical neurons. The authors assessed psychostimulant responses in
      parkinsonian patients to test whether intact dopaminergic systems are required
      for subjective psychostimulant effects. Responses to placebo and 15, 20, 25, and
      30 mg of methylphenidate were studied in 12 parkinsonian patients and 12
      neurologically intact matched controls. Physiological and subjective mood
      responses were recorded using the Profile of Mood States, Addiction Research
      Center Inventory, and Visual Analog Scale. Drug-induced changes in "good"
      feelings and overall drug responses were attenuated in the parkinsonian patients.
      These results, in conjunction with animal data, provide support for dopamine
      hypotheses of psychostimulant reward in humans and suggest possible bases for
      some of the mood disturbances found in many parkinsonian patients.

PMID- 9526148
TI  - Inhalation of 30% nitrous oxide impairs people's learning without impairing
      people's judgments of what will be remembered.
AB  - Many hypotheses have been proposed to account for the effects of nitrous oxide on
      memory, with one emerging possibility being that it has a global effect on memory
      related functioning. This possibility was explored by examining the effects of
      nitrous oxide on memory performance and on the accuracy of people's judgments
      about their memory performance. Participants inhaled 30% nitrous oxide or a
      placebo gas while items were studied and while judgments were made about the
      likelihood of recall for each item. Next, all participants inhaled the placebo
      during paired-associate recall. Although administration of nitrous oxide during
      study impaired recall, it did not affect the predictive accuracy of the
      metacognitive judgments. These results provide pharmacological evidence for a
      distinction between memory and metamemory.

PMID- 9526149
TI  - Behavioral effects of caffeine and other methylxanthines on children.
AB  - Subjective, performance-enhancing, dependence-producing, and adverse effects of
      methylxanthines are examined, based on computerized searches (i.e., Medline and
      PsycLIT). High doses (> 3 mg/kg) of caffeine in children who consume little
      caffeine produce negative subjective effects such as nervousness, jitteriness,
      stomachaches, and nausea. Whether lower doses produce positive subjective effects
      has not been adequately tested. Caffeine appears to slightly improve vigilance
      performance and decrease reaction time in healthy children who habitually consume
      caffeine but does not consistently improve performance in children with attention
      deficit-hyperactivity disorder. Early studies suggest caffeine self
      administration and withdrawal can occur in some adolescent soda drinkers.

PMID- 9526150
TI  - Pain inhibition, nicotine, and gender.
AB  - The ability of nicotine to decrease sensitivity to pain in humans has been a
      subject of dispute. Decreased sensitivity has been demonstrated in studies
      involving men, whereas the effect has been less obvious or absent in studies
      involving predominantly, or entirely, women. To determine whether there are
      gender differences in nicotine's hypoalgesic actions, ratings of electrocutaneous
      stimulation were obtained from 30 male and 44 female smokers and nonsmokers under
      placebo and nicotine conditions. Nicotine increased the pain threshold and
      tolerance ratings of men but had no effect on the pain ratings of women. Among
      men, there was no effect of smoking history, suggesting that the changes in pain
      perception reflect a direct pain-inhibitory effect of nicotine rather than a
      relief from acute nicotine withdrawal. Nicotine had no effect on mood or task
      ratings, indicating that the antinociceptive effects observed were not due to
      nicotine's putative mood effects.

PMID- 9526151
TI  - Drug addiction as a physical disease: the role of physical dependence and other
      chronic drug-induced neurophysiological changes in compulsive drug self
      administration.
AB  - Physical-dependence-based theories of addiction regard compulsive drug taking as
      the behavioral manifestation of a desperate need to relieve aversive autonomic
      withdrawal symptoms. In the present article, the withdrawal-relief paradigm, or
      opiate model of addiction, is critically examined in the light of recent
      experimental and clinical evidence for various addictive drugs. It is concluded
      that contrary to the opiate model, the constellation of pathological behaviors
      defining addiction (compulsive drug use, craving, loss of control, and a
      persistent tendency to relapse) does not primarily reflect a need to relieve
      actual or conditioned autonomic withdrawal symptoms. Recent theories of addiction
      emphasize the positive reinforcing properties of drugs and sensitization of brain
      dopamine systems rather than negative reinforcement or drug-opposing
      neuroadaptations. Despite the failure of the opiate model, recent evidence
      suggests that persistent drug-induced changes in the physical brain may underlie
      addictive behavior, consistent with the general notion of addiction as a physical
      disease.

PMID- 9526152
TI  - Nonvascularized toe proximal phalanx transfers in the treatment of aphalangia.
AB  - The indications for nonvascularized toe phalanx transfers are limited.
      Radiolucency in the region of the transferred physis does not necessarily
      indicate a functional growth plate. Older age is not a contraindication to toe
      phalanx transfers. The results of this procedure can be improved and information
      from experimental physeal transplantation may help the surgeon to improve
      technique.

PMID- 9526153
TI  - Thumb duplication.
AB  - Thumb duplication is a complex congenital anomaly. Treatment requires a detailed
      understanding of the pathophysiology as well as an appreciation of all the
      components involved. The goals of surgery are to restore the normal anatomic
      relationships of the residual thumb. Successful reconstruction requires
      evaluation and correction of the bony axis; articular congruity; size and
      angulation; intrinsic and extrinsic musculotendinous abnormalities; and ligament,
      skin, and soft-tissue elements. The reconstructed thumb may not match the normal
      thumb because of the hypoplasia that is inherently associated with the condition.
      With careful preoperative planning and attention to detail, however, a
      satisfactory cosmetic and functional result can be achieved.

PMID- 9526154
TI  - Congenital constriction band syndrome.
AB  - Constriction band syndrome is a fairly common congenital hand disorder. Proposed
      etiologies for the formation of the anomalies are reviewed in this article and
      demographics for the syndrome are presented. Varied clinical presentations are
      addressed and potential treatment options are reviewed.

PMID- 9526155
TI  - Congenital radial head dislocations.
AB  - Congenital radial head dislocation is the most common congenital elbow
      abnormality. Patients generally remain asymptomatic until adolescence and, at
      that time, may benefit from radial head resection. Open reduction and ligament
      reconstruction may offer advantages over late radial head resection if performed
      before the age of 2 years. Further long-term studies are needed to determine if
      open reduction and ligament reconstruction are helpful.

PMID- 9526157
TI  - Ulnar ray deficiency.
AB  - Longitudinal deficiencies of the ulna are very rare deformities. Despite the
      cosmetic appearance, patients usually have very functional extremities. The limb
      function has been adversely related to ipsilateral hand deformities and
      radiohumeral synostosis. Surgical treatment should be aimed at correcting such
      deformities. It is prudent to wait and observe patients before definitive wrist
      or forearm treatment is recommended.

PMID- 9526156
TI  - Finger polydactyly.
AB  - Polydactyly is one of the most common congenital differences. Duplications of the
      index finger, central rays, and small digit each have unique characteristics and
      associations. Complex anomalies such as the mirror hand and pentadactyly
      represent specialized forms of polydactyly. The goal of reconstructing a
      functional hand is met by appreciating the anatomic variations and systemic
      implications, then employing the challenging technical and intellectual concepts
      described.

PMID- 9526158
TI  - Congenital clasped thumb.
AB  - Congenital clasped thumb is a disorder characterized by flexion posture of the
      thumb secondary to extensor side underdevelopment, flexor side tightness, or
      both. Mild cases may be treated by splintage whereas more advanced cases require
      tendon transfer or a combination of tendon transfer and flexor side releases.
      Clasped thumb can be seen in conjunction with syndromes such as arthrogryposis
      and, in these cases, recognition of the abnormal anatomic structures is required
      to effect satisfactory reconstruction.

PMID- 9526159
TI  - Radial longitudinal deficiency. A review and update.
AB  - Treatment of patients with radial longitudinal deficiency remains challenging for
      the hand surgeon. A thorough knowledge of the anomalous anatomy and the varied
      presentation is vital to effect a sound treatment plan. This article includes a
      review of the pertinent historical background, a discussion of current
      recommendations, and a detailed critical review of recent contributions to the
      field.

PMID- 9526160
TI  - Diagnosis and treatment of congenital thumb hypoplasia.
AB  - The hypoplastic thumb has a variety of presentations, which have been generalized
      into a formal classification system that has treatment implications. In most
      cases, the spectrum of hypoplasia has predictable deficits in terms of tendon and
      bone absence. The ultimate goal is always the same--to enhance usage of the
      radial digit. In this article, a straightforward, reliable, and reproducible
      surgical technique is discussed and illustrated. Pitfalls, indications, and
      treatment regimes also are discussed to help the physician successfully treat the
      child with a hypoplastic thumb.

PMID- 9526161
TI  - Spastic hemiplegia of the upper extremity in children.
AB  - Care of upper extremity problems in hemiplegic children requires careful
      evaluation and planning. This article focuses on the evaluation and treatment of
      spastic hemiplegia attributable to cerebral palsy. All treatments must take into
      consideration the level of static and dynamic motor deformity; levels of
      discriminatory sensibility, intelligence, and motivation; and overall level of
      function. The treatments discussed are designed to improve the child's
      musculoskeletal condition but do not cure the underlying disease.

PMID- 9526162
TI  - Microvascular surgery in the reconstruction of congenital hand anomalies.
AB  - Several congenital upper extremity anomalies may be treated using micro-surgical
      techniques. Long-term studies have shown the usefulness of microvascular toe
      transfer in the treatment of adactyly with the incorporation of the transferred
      digit into grasp-and-pinch function. The use of free fibular transfer for long
      bone deformities of the forearm has been shown to provide bony union as well as
      growth. Factors that must be considered include patient age, vessel availability,
      and lack of other possible reconstructive options.

PMID- 9526163
TI  - Complications of duplicate thumb reconstruction.
AB  - Thumb duplication is a common anomaly treated by most hand surgeons. Successful
      reconstruction of this disorder requires the surgeon to address abnormalities of
      collateral ligaments, tendon, and bone. With growth, secondary problems may
      occur, including bony overgrowth, tendon imbalance, and joint stiffness. Surgeons
      must be aware of these potential complications when the performance of initial
      surgery and long-term follow-up of the child are necessary.

PMID- 9526164
TI  - Screening 25 dystrophin gene exons for deletions in Arab children with Duchenne
      muscular dystrophy.
AB  - Forty-two Arab children with Duchenne muscular dystrophy (DMD) were studied for
      intragenic deletions in 25 exons of the dystrophin gene using three different
      multiplex PCR sets each amplifying a total of 9, 9 and 6 different exons,
      respectively. Exon 22 was amplified individually. Deletions were found in 78, 76
      and 12% of DMD patients with each of the three sets, respectively. With all the
      three sets, the detection rate increased to 86% (36 of 42 patients). Fifty
      percent of the deleted exons were located in the distal hot spot, 8% in the
      proximal hot spot while 42% were scattered over both. This study, the first in an
      Arab population and only the second to use three PCR multiplex sets, documents
      one of the highest deletion detection rates in DMD.

PMID- 9526165
TI  - A conditional inference framework for extending the transmission/disequilibrium
      test.
AB  - The transmission/disequilibrium test (TDT) of Terwilliger and Ott [Hum Hered
      1992;42:337-346] and Spielman et al. [Am J Hum Genet 1993;52:506-516] is widely
      used to detect linkage and/or association between a genetically influenced
      disease and the alleles of a codominant marker locus. The TDT was specifically
      designed to avoid the spurious population associations produced by ethnic
      stratification of a sample of affected people. In this paper, we describe
      permutation extensions of the TDT that share this advantage. Our conditional
      inference framework permits extensions to multiple alleles, multiple loci,
      unaffected siblings, and genotypic rather than allelic associations. In the case
      of multiple loci, the conditional perspective provides a straightforward
      correction for multiple tests that can be substantially more powerful than the
      standard Bonferroni correction.

PMID- 9526166
TI  - Fluorescence in situ hybridization of psu dic(X)(Xpter-Xq21::Xq21-Xpter) in two
      patients with Turner's syndrome.
AB  - Dicentric X chromosomes of different derivations were present in 6 out of a total
      of 42 patients with Turner's syndrome. The most unusual cases were observed in 2
      patients having a psu dic(X)(Xpter-Xq21::Xq21-Xpter) in mosaic form who were
      examined by fluorescence in situ hybridization. Alu-PCR products from hybrid cell
      lines were used as partial chromosome paints for the p arm of the human X
      chromosomes. The other 4 patients displayed isodicentric idic(Xq) in mosaic form.
      One of the patients displayed 9 cell lines originating from the accumulation of
      isodicentric idic(Xq) chromosomes, along with loss of chromosome material which
      resulted in fragments of varying size.

PMID- 9526167
TI  - A novel missense mutation in the DNA mismatch repair gene hMLH1 present among
      East Asians but not among Europeans.
AB  - In a search for germline mutations in the DNA mismatch repair genes hMSH2 and
      hMLH1 in Chinese patients with colorectal cancer we identified a novel missense
      mutation (V384D) in exon 12 of the hMLH1 gene in 4 out of 26 individuals. This
      mutation had not been observed in any of 109 German patients who either fulfill
      the clinical criteria of hereditary nonpolyposis colorectal cancer or had
      developed colorectal cancer at an early age. In a second series of experiments,
      DNA samples of 80 healthy. Japanese and 100 healthy Germans were examined for the
      presence of the V384D mutation. It was observed in 4 Japanese, but in none of the
      German individuals. Thus, the V384D mutation seems to be confined to the East
      Asian population. Since this missense mutation occurs at a less conserved region
      of the hMLH1 gene, it may represent a nonfunctional polymorphism. However, a role
      in the pathogenesis of colorectal cancer cannot be ruled out from the present
      study.

PMID- 9526168
TI  - G6PD variants in three South American ethnic groups: population distribution and
      description of two new mutations.
AB  - A review is made of G6PD population surveys conducted in 4,558 European-derived,
      2,484 admixed Black/Indian/White or Black/White, and 10,298 Indian subjects
      living in South America. Despite the fact that twice more Amerindians than Whites
      had been examined, no autochtonous variant was found among them, while seven
      different types (besides the most common Gd*B, Gd*A, Gd*A- and Gd*Med) were
      observed among the Whites. We also describe two new mutations in the G6PD
      molecule (Farroupilha, 977 C-->A and Lages, 40 G-->A), bringing the number of
      mutants characterized to 98. G6PD Lages is the most 5' mutation detected thus
      far. G6PD Seattle, previously found in the United States and Italy, seems to
      occur in other European countries and was observed by us in five independent
      Brazilian families.

PMID- 9526169
TI  - Extreme selection strategies in gene mapping studies of oligogenic quantitative
      traits do not always increase power.
AB  - It is well known that obtaining adequate statistical power to detect linkage to
      or association with genes for complex quantitative traits can be very difficult.
      In response, investigators have developed a number of power-enhancing strategies
      that consider restraints such as genotyping (and/or phenotyping) costs. In the
      context of both association and sib pair linkage studies of quantitative traits,
      one of the most widely discussed techniques is the selective sampling of
      phenotypically extreme individuals. Several papers have demonstrated that such
      extreme sampling can markedly increase power (under certain circumstances).
      However, the parenthetical phrase in the previous sentence has generally not been
      made explicit and it appears to be implied that the more phenotypically extreme
      the individuals, the more power one has. In this paper, we show by simulation
      that this is not true under all circumstances. In particular, we show that under
      oligogenic models, where some biallelic quantitative trait loci (QTLs) have
      markedly asymmetric allele frequencies and large mean displacement among
      genotypes, and others have less asymmetric allele frequencies and smaller mean
      displacement among genotypes, power to detect linkage to or association with the
      latter QTL can actually decrease by sampling more extreme sib pairs. This
      suggests that more extreme sampling is not always better. The 'optimal' sampling
      scheme may depend on both what one suspects the underlying genetic architecture
      to be and which of the oligogenic QTL one has greatest interest in detecting.

PMID- 9526170
TI  - Saami mitochondrial DNA reveals deep maternal lineage clusters.
AB  - The mitochondrial DNA of 62 Saami from the north of Norway was analyzed in the D
      loop hypervariable region I and II and sequences were compared to other gene
      pools. Two major (lineage 1 and 2) and two minor (lineage 3 and 4) maternal
      lineage clusters were found. Lineage 1 (56.9% of all hitherto analyzed Saami
      samples) contains a substantial number of branching haplotypes which are unknown
      in European gene pools. Lineage 2 (31.5%) and lineage 4 (3.6%) have few branching
      points and are present at a low rate throughout European gene pools. Lineage 3
      (4.7%) has polymorphisms characteristic of circumpolar lineages.

PMID- 9526171
TI  - An adenine trimer precedes a C/G polymorphism in the 3'-amplimer region of the
      human platelet glycoprotein IIIa intron 6 CT repeat.
AB  - Restriction enzyme and short tandem repeat polymorphisms are often used to link a
      particular allele with an inheritable disease-related gene in the absence of the
      information regarding the DNA mutation or defect. Polymorphic markers within the
      gene in question are particularly useful and can provide sufficient information
      for genetic counselling to potential carriers of the disease. Using a published
      method for the CT repeat in intron 6 of the GP3A gene, it was found that a single
      nucleotide deletion in the published genomic GP3A sequence in the region of the
      antisense amplimer and a C/G nucleotide polymorphism (allele frequencies, G =
      0.883, C = 0.117) immediately adjacent to the deletion were responsible for the
      lack of PCR amplification. The absence of amplification has important
      implications for the assignment of a particular CT repeat to a given allele and
      for the population frequencies of the various CT repeats.

PMID- 9526172
TI  - A novel mutation Q602STOP in exon 12 of the FVIII gene.

PMID- 9526173
TI  - Lansoprazole elevates the ratio of serum pepsinogen I v.s. pepsinogen II.
AB  - In order to investigate the mechanism by which proton pump inhibitor increases
      serum pepsinogen levels, we evaluated the effects of ulcer location and IgG
      antibody against Helicobacter pylori on lansoprazole-induced elevations. Patients
      with endoscopically proven peptic ulcer received lansoprazole 30 mg/day for 6 or
      8 weeks; pepsinogen I and II levels, along with antibody to H. pylori, were
      measured in fasting blood samples. We found that whether or not antibody to H.
      pylori was present, pepsinogen I and II levels and the I/II ratio rose
      significantly in lansoprazole-treated patients. Patients with stomach-body ulcers
      showed smaller increases in both pepsinogens than did those with ulcers in the
      gastric angle/antrum or in the duodenum. In conclusion, lansoprazole increases
      serum levels of both pepsinogens I and II, although a larger increase in
      pepsinogen I elevates the pepsinogen I/II ratio. The relatively small increases
      seen in patients with stomach-body ulcers suggest atrophic changes in the gastric
      mucosa in patients with stomach-body ulcer.

PMID- 9526175
TI  - Effect of acute carnitine administration on glucose insulin metabolism in healthy
      subjects.
AB  - The authors evaluated the effect of carnitine on glucose insulin metabolism.
      Twenty-five subjects free from metabolic disorders or serious functional
      alterations in the liver, kidneys or myocardium were studied. All were infused
      with a 5% glucose-enriched solution (Group A); 48 h later the same subjects were
      infused with a 5% glucose solution containing 2g carnitine (Group B). Variations
      in blood glucose and insulin levels and range were measured at different times
      during and after infusion. Study results showed that the administration of
      carnitine lead to an improvement in glucose metabolism, as demonstrated by a
      saving in insulin secretion accompanied, at least on a temporary basis, by a
      corresponding decrease in blood glucose which, however, remained within normal
      parameters.

PMID- 9526174
TI  - Potential interest of anti-ischemic agents for limiting cyclosporin A
      nephrotoxicity.
AB  - Chronic administration of cyclosporin A induces nephrotoxicity in humans. This is
      related to a cyclosporin A-induced constriction of afferent glomerular arterioles
      and mesangial cells, which leads to a decrease in filtration pressure and
      creatinine clearance. Afterwards, cellular lesions are observed involving mainly
      tubular atrophy and interstitial fibrosis, both of which are nonspecific. The
      initial mechanism of its toxicity is not clearly explained. The current
      pharmacological approach is symptomatic in order to counteract or minimize the
      consequences of a prime cause, which still remains to be defined. However,
      cyclosporin A has a deletereous effect on mitochondrial functions and mainly on
      ATP synthesis, which occurs when Ca2+ accumulates in matrix mitochondria. The
      effects of trimetazidine, an antischemic drug used in the treatment of angina
      pectoris, have been assessed. This drug is effective in experimental models of
      hypoxia induced by cyclosporin A: it restores ATP synthesis previously decreased
      by Ca2+ and cyclosporin A, and releases a part of Ca2+ excess accumulated by
      mitochondria at concentrations reached in humans at usual dosage regimens. At
      higher concentrations, it reverses the mitochondrial permeability transition
      previously generated (opened) by Ca2+ and a pro-oxidant such as terbutylperoxide
      (t-BH). It was also observed that trimetazidine does not modify the
      immunosuppressive effects of cyclosporin A in various models. These data suggest
      that nephrotoxicity of cyclosporin A is not irrevocably linked to its
      immunosuppressive effect but that it may be possible to counteract at least
      partly its nephrotoxic effects without altering its effectiveness in preventing
      graft rejection.

PMID- 9526176
TI  - Cytokine levels in osteoarthrosis patients undergoing mud bath therapy.
AB  - Osteoarthritis is an important rheumatic condition characterized by the
      progressive destruction of cartilage. The pathophysiologic phenomena leading to
      the pathologic changes in the joint appear to result from biomechanical factors
      and activation of final common pathways of tissue damage influencing chondrocyte
      homeostasis and a functional program. Several cytokines and growth factors are
      reported to be responsible for inflammation and cartilage degradation. Among
      these, IL-1 and TNF alpha have been suggested as important in promoting cartilage
      inflammation and tissue destruction, while IGF I has a protective influence on
      cartilage structure. Chondrocytes and their metabolism have gained interest as
      targets of drug intervention; the results of this study confirm that mud bath
      therapy is also able to influence chondrocyte activities. Our data suggest that
      mud bath therapy influences cytokines related to osteoarthrosis pathomechanism
      and maintenance, and encourage further investigations to evaluate possible
      synergism between pharmacological treatment and mud bath therapy.

PMID- 9526177
TI  - Circadian changes in body temperature during the menstrual cycle of healthy adult
      females and patients suffering from premenstrual syndrome.
AB  - The biological rhythm of females is closely related to the menstrual cycle, and
      this rhythm is believed to influence circadian changes in body temperature. This
      study investigated and compared the patterns of circadian changes in the body
      temperature of healthy adult females and patients suffering from premenstrual
      syndrome or major depression. Body temperature was measured both rectally and
      sublingually in healthy subjects, and only sublingually in the patients. During
      the luteal phase in healthy adult females, both the average and lowest nocturnal
      body temperatures increased, the amplitude of the circadian changes decreased,
      and the times of the lowest and highest temperatures within a 24-hour period were
      delayed by 2-3 h. In the patients, the amplitude decreased during disease
      periods, especially in the follicular phase, whereas in the luteal phase,
      circadian changes showed great variation each day, although the decrease in
      amplitude was not as remarkable. The results show that (i) the biological rhythm
      of females is intrinsically unstable in the luteal phase, although this rhythm is
      stable in the follicular phase; and, (ii) symptoms were often aggravated with the
      decreases in amplitude experienced in the luteal phase.

PMID- 9526178
TI  - The relationship between anxiety disorders and age.
AB  - OBJECTIVES: To review the major community-based epidemiological studies that have
      reported data on anxiety disorders in individuals aged 65 and over and to examine
      age-related changes in their prevalence and incidence. DATA SOURCES AND STUDY
      SELECTION: All English language entries relating to anxiety in the BIDS, EMBASE,
      Medline and PsychLit computerized databases, together with a search of relevant
      citations. DATA SYNTHESIS: The prevalence of phobic disorders in the population
      aged 65 or over lies between 0.7% and 12% over a 1-6-month period. As the rates
      for social phobia, 1%, and simple phobia, 4%, are fairly consistent, much of this
      variation is due to agoraphobia, whose prevalence lies between 1.4% and 7.9%. The
      prevalence of obsessive-compulsive disorder is 0.1-0.8%, panic disorder 0.1% and
      generalized anxiety 4%. Women do have a higher prevalence of anxiety disorders
      than men but this difference diminishes with increasing age, as does the apparent
      prevalence of all anxiety disorders apart from generalized anxiety, measured
      without hierarchical rules, which appears to be maintained or increase. The
      relative importance of various explanations for this apparent reduction is
      discussed, including the three that are of greatest public health and clinical
      importance: cohort effects, anxiety-related mortality and comorbidity between
      anxiety and cognitive impairment. A tri-dimensional approach (psychic, somatic
      and behavioural) to anxiety measurement is advocated in order to facilitate
      future studies of age-related changes which may lead to a reappraisal of the
      status of generalized anxiety as a 'residual category'.

PMID- 9526179
TI  - A double-blind comparison of the efficacy and safely of paroxetine and imipramine
      in the treatment of depression with dementia.
AB  - OBJECTIVES: To compare the efficacy of paroxetine and imipramine prospectively in
      patients with coexisting depression and dementia. METHODS: An 8-week, double
      blind, parallel group trial comparing paroxetine 20-40 mg/day with imipramine 50
      100 mg/day in 198 patients aged 60 years or over with a Montgomery-Asberg
      Depression Rating Scale (MADRS) score > or = 20 and a Folstein mini-mental state
      evaluation score of 17-23 points after a 3- to 7-day placebo run-in period.
      RESULTS: Both paroxetine and imipramine reduced the MADRS and the Clinical Global
      Impression (CGI) severity-of-illness and global improvement scores at weeks 2, 4,
      8 and at endpoint, with no significant differences between treatment groups at
      any timepoint (MADRS, p > or = 0.368; cgi, p > or = 0.286). There was a
      statistically significant difference in favour of paroxetine at both the week 4
      and week 8 timepoints (analysis of variance, p < or = 0.049) in the Cornell scale
      for depression in dementia: at endpoint there was no significant difference
      between treatments (p = 0.103). Treatment-emergent adverse experiences were
      reported by 51.5% (51/99) of patients treated with paroxetine and 50.5% (50/99)
      of patients treated with imipramine. Anticholinergic adverse experiences
      (paroxetine 6.1%; imipramine 13.1%) and serious non-fatal adverse experiences
      (paroxetine 4.0%; imipramine 8.1%) were reported by more patients in the
      imipramine group than in the paroxetine group. CONCLUSIONS: Paroxetine and
      imipramine were both effective in the treatment of depression in elderly subjects
      with co-existing dementia, and no significant differences were detected between
      the groups. There were trends suggesting that paroxetine was better tolerated
      than imipramine in terms of anticholinergic adverse experiences and serious non
      fatal adverse experiences.

PMID- 9526180
TI  - Clinical predictors of aggressive behaviour in Alzheimer's disease.
AB  - OBJECTIVES: To examine the level and clinical correlates of aggressive behaviour
      in Alzheimer's disease (AD). METHOD: Seventy patients with probable AD were rated
      using validated assessment instruments including the Rating Scale for Aggressive
      Behaviour in the Elderly (RAGE). RESULTS: Thirty-one subjects were rated as at
      least mildly aggressive during the 3-day period prior to assessment. RAGE scores
      correlated significantly with delusions and activity disturbance scores.
      Aggressive behaviour was not associated with age, sex, dementia severity,
      hallucinations or depression. CONCLUSIONS: Aggressive behaviour occurs frequently
      in patients with AD. Our results confirm the findings of previous studies that
      the presence of delusions increases the risk of aggression in this population.

PMID- 9526181
TI  - Stealing lately: a case of late-onset kleptomania.
AB  - The case of a 77-year-old woman first diagnosed with kleptomania is presented to
      indicate a possible late-onset course of this disorder. Particularly striking
      about this patient's history of shoplifting behaviors was the absence of an onset
      prior to the age of 73. Her pattern of stealing did not begin at an early age,
      and was not sporadic or episodic over the course of several years. The treatment
      course and patient outcome are discussed in light of DSM-IV diagnostic criteria.

PMID- 9526182
TI  - Influences on the care of demented elderly people in the People's Republic of
      China.
AB  - The elderly population of the People's Republic of China is increasing rapidly.
      Yet few studies of dementia have been carried out outside the large cities.
      Prevalence rates are approaching those in the West. Influences on the system of
      care for demented old people include the growth of one-child families; decreasing
      levels of filial care; changing levels of residential care provision; a low level
      of specialist medical care and other welfare services; a low level of public
      awareness of dementia; and the weakening of the extended family, associated
      especially with urbanization and the increasing mobility of labour. These trends
      may create a difficult situation for dementia sufferers and their carers.

PMID- 9526183
TI  - Geriatric psychiatry in Australia.

PMID- 9526184
TI  - SSRI-induced hyponatraemia.

PMID- 9526186
TI  - Current awareness in geriatric psychiatry.

PMID- 9526185
TI  - The community study of psychiatric disorders in elderly from the Indian
      subcontinent living in Bradford.

PMID- 9526187
TI  - Establishing a united front against the injustice of tuberculosis.

PMID- 9526188
TI  - More on "what's in a name ... "--pragmatism in mycobacterial taxonomy.

PMID- 9526189
TI  - Two excellent management tools for national tuberculosis programmes: history of
      prior treatment and sputum status at two months.

PMID- 9526190
TI  - Population dynamics of tuberculosis treatment: mathematical models of the roles
      of non-compliance and bacterial heterogeneity in the evolution of drug
      resistance.
AB  - SETTING: Patient non-compliance and/or spatial heterogeneity in drug
      concentration or effectiveness may contribute to the emergence of drug resistance
      during multiple-drug chemotherapy of tuberculosis. OBJECTIVE: Using mathematical
      models of mycobacterial population dynamics under antimicrobial treatment, to
      assess the effects of non-compliance, heterogeneity and other factors on the
      success of treatment. DESIGN: A mathematical model is used to generate
      predictions about the ascent of drug resistance in treated hosts with non
      compliance and/or a 'protected compartment' of bacteria where only one drug is
      active; simulations of a more realistic version of this model take into account
      random mutation, and different assumptions about the size of, and growth rate of
      bacteria in, the protected compartment. RESULTS: The existence of a protected
      compartment can increase the likelihood of resistance to the single drug active
      in that compartment, but only if bacteria resistant to that drug can grow in the
      protected compartment or if the host is non-adherent to the treatment regimen.
      However, the protected compartment may also slow the ascent of bacteria resistant
      to drugs not active in it (e.g. isoniazid) by providing a reservoir of non
      selected mycobacteria. The model predicts that relative rates of killing are more
      important than mutation rates in determining the order in which resistant mutants
      ascend. Model predictions, in combination with data about drug resistance
      patterns, suggest that non-compliance, but not heterogeneity, is an important
      cause of treatment failure. CONCLUSION: Patterns of acquired drug resistance may
      be used to infer processes of selection during treatment; mathematical models can
      aid in generating predictions about the relative impacts of treatment parameters
      in the evolution of resistance, and eventually in suggesting improved treatment
      protocols.

PMID- 9526191
TI  - Does the efficacy of BCG decline with time since vaccination?
AB  - OBJECTIVE: To investigate whether the protective efficacy of bacille Calmette
      Guerin (BCG) against tuberculosis decreases with time since vaccination. DESIGN:
      A quantitative review of all 10 randomized trials of BCG against tuberculosis in
      purified protein derivative (PPD)-negative individuals, that presented data for
      discrete periods. For each trial, we derived log rate ratios for the annual
      change in the efficacy of BCG. We also compared efficacy in the first two years,
      and the first 10 years, to that in the rest of the trial. RESULTS: There was
      considerable heterogeneity between trials in the annual change in the efficacy of
      BCG. In seven efficacy decreased overtime, while in three it increased. Average
      annual change in efficacy was not related to overall efficacy. Efficacy also
      varied between trials in the first two years after vaccination, at more than two
      years after vaccination and in the first ten years after vaccination. However the
      variation in efficacy between trials more than 10 years after vaccination was not
      statistically significant (P = 0.26). We therefore calculated that the average
      efficacy more than 10 years after vaccination was 14% (95% confidence interval 
      9% to 32%). CONCLUSION: BCG protection can wane with time since vaccination.
      There is no good evidence that BCG provides protection more than 10 years after
      vaccination.

PMID- 9526192
TI  - Acceptance of isoniazid preventive treatment by close contacts of tuberculosis
      cases: a 692-subject Italian study.
AB  - SETTING: Villa Marelli Institute, Lombardy Regional Reference Centre for
      Tuberculosis. OBJECTIVE: To evaluate acceptance of and adherence to isoniazid
      preventive treatment (IPT) of close contacts of contagious tuberculosis (TB)
      cases (CC); comparison of Italian and immigrant patients. METHODS: A
      retrospective study of a consecutive series of 692 subjects (474 Italians and 218
      immigrants from developing countries) exposed to contagious TB cases, who were
      offered IPT after tuberculin skin testing and chest X-ray, according to the
      Lombardy Regional Protocol for TB control. RESULTS: Of 692 CCs, 36 (5.2%)
      subjects refused IPT, 522 (75.5%) completed the treatment as prescribed, 23
      (3.3%) suspended IPT because of adverse effects, 14 (2.0%) spontaneously
      discontinued IPT against our advice, 93 (13.4%) were lost to follow up, and seven
      (0.6%) were still in treatment when the present data were evaluated. Italian CCs
      had a completion rate significantly higher than the immigrants (81.0% vs 63.3%, P
      < 0.01). CONCLUSION: The rate of acceptance and completion of IPT in our
      population proved higher than many previously reported data, and the better
      results among Italian subjects reflect the importance of a complete comprehension
      of IPT that may not always be achieved with immigrant patients.

PMID- 9526193
TI  - Tuberculosis notifications in England: the relative effects of deprivation and
      immigration.
AB  - SETTING: Metropolitan areas of England, including London boroughs, in 1991.
      OBJECTIVE: To investigate the relative importance of deprivation, immigration and
      the elderly in explaining variations in tuberculosis rate. DESIGN: A
      retrospective study using multiple Poisson regression models to assess the
      interrelationship between various population parameters. RESULT: Significant
      differences ere observed between London and other metropolitan districts in the
      measures of tuberculosis, immigration and the elderly. In addition, all
      population parameters were significantly intercorrelated in London: areas with a
      high proportion of immigrants had high levels of deprivation and low proportions
      of elderly. In other metropolitan districts, only immigration and the Jarman
      index were significantly associated, and removing the immigration component from
      the index removed this statistical significance. Multiple Poisson regression
      models revealed that the immigrant index had the strongest explanatory power in
      explaining tuberculosis rates, but there were significant interactions between
      this and measures of urban deprivation indices. That is, there was a greater
      effect of increasing deprivation at lower levels of immigration than at higher
      levels. This phenomenon was more pronounced in London boroughs than other
      metropolitan districts. The elderly index had no significant influence on
      tuberculosis rates. CONCLUSION: Although the association between tuberculosis and
      deprivation previously reported for the city of Liverpool is confirmed across all
      urban areas of England, the immigrant proportion of the population has a greater
      statistical power in explaining variations in rates of urban tuberculosis.
      However, tuberculosis notifications can be most accurately predicted by combining
      both measures than by either one alone.

PMID- 9526194
TI  - Tuberculosis in a cohort of Vietnamese refugees after arrival in Denmark 1979
      1982.
AB  - SETTING: Department of Infectious Diseases, Rigshospitalet, Copenhagen, Denmark.
      OBJECTIVE: To study the occurrence of tuberculosis (TB) in a cohort of immigrants
      from a high incidence country during the years following arrival in a low
      incidence country. DESIGN: Follow-up analysis in a cohort of 1983 Vietnamese
      refugees who arrived in Denmark during the period 1979-1982. The civil
      registration number could be identified for 1936 (98%) individuals from the
      original cohort. Date of possible death, emigration and the development of
      tuberculosis were determined by checking the refugees' civil registration number
      in the National Civil Register and the National Infectious Disease Registry for
      Tuberculosis. RESULTS: Tuberculosis notification for the 1936 individuals fell
      from 1.14% for the first 12 months to a mean of 0.08% per year during the
      following 5-year period. During the 16 years of follow up, 36 of the refugees
      developed tuberculosis, of whom 14 (39%) had had abnormal chest X-ray on arrival
      and 14 (39%) (including one with normal chest X-ray) had been identified as
      having active tuberculosis through screening on arrival. CONCLUSION: Decline in
      tuberculosis incidence for immigrants is very rapid if the tuberculosis infection
      rate is low following arrival. With a very limited TB screening programme (chest
      X-ray on arrival) and a passive diagnosis policy without preventive chemotherapy,
      it is possible to control tuberculosis among high prevalence immigrants in a low
      incidence country.

PMID- 9526196
TI  - Traditional healers and pulmonary tuberculosis in Malawi.
AB  - SETTING: Queen Elizabeth Central Hospital (QECH) and Blantyre district, Malawi.
      OBJECTIVE: To investigate the use that tuberculosis (TB) patients in Malawi make
      of traditional healers and traditional medicine. DESIGN: A questionnaire study
      was carried out on 89 smear-positive pulmonary TB patients admitted to QECH.
      Seven traditional healers in Blantyre were also interviewed about their
      knowledge, attitudes and practice of patients whom they considered to have TB.
      RESULTS: Of the 89 patients, 33 (37%) visited a traditional healer before seeking
      regular medical care. Patients spent a median length of 4 weeks with the
      traditional healer. During this time, 24 patients did not improve or deteriorated
      while on traditional treatment. No patient was referred to the medical services
      by the traditional healer. All traditional healers claimed to know about TB. Four
      said they would refer a patient to hospital if their treatment was not curative.
      In 1995, six traditional healers claimed to have cured 116 patients with TB.
      CONCLUSION: It is important to involve traditional healers in the educational
      activities of the National TB Control Programme. These healers need to be taught
      to recognise and refer patients with TB, whom they should not treat, but at the
      same time be encouraged to administer safe treatments for conditions which are
      more amenable to their practice.

PMID- 9526195
TI  - Physician compliance with national tuberculosis treatment guidelines: a
      university hospital study.
AB  - SETTING: The Aga Khan University Hospital, in Karachi, Pakistan, is a 650-bed
      university teaching hospital. OBJECTIVES: There is little data from Pakistan on
      the awareness and application of the World Health Organization (WHO)'s
      tuberculosis treatment guidelines among physicians. This study evaluates
      physician compliance with these guidelines. DESIGN: A questionnaire to measure
      physician compliance was developed, pilot tested and standardised. Case records
      of all patients hospitalized with tuberculosis were reviewed (January-December
      1995, n = 229), and were classified into WHO Category 1 (n = 191), Category 2 (n
      = 9) and Category 3 (n = 29). RESULTS: A total of 53 (23%) patients had a
      diagnostic bacteriological sputum smear examination, of which 38% were smear
      positive and 47% culture positive. Of 25 cerebrospinal fluid cultures 12% were
      positive. No sputum smear tests were conducted during treatment. Of 58 patients
      in Category 1 who completed therapy 74% received a 2-month intensive phase
      consisting of HRZE (isoniazid, rifampicin, pyrazinamide, ethambutol) (n = 43),
      while 41% received a 6 month continuation phase with HE (n = 24). Over 70%
      patients were lost to follow up, more than half of these during the intensive
      phase. CONCLUSION: Our study reflects poor awareness of the WHO guidelines and
      low compliance among physicians, and a high loss to follow-up. Efforts are needed
      to create physician awareness about the WHO guidelines and their use. This study
      can be used to assess the effectiveness of any future physician education and to
      identify areas of weakness in health care.

PMID- 9526197
TI  - Cost-effectiveness of the polymerase chain reaction versus smear examination for
      the diagnosis of tuberculosis in Kenya: a theoretical model.
AB  - SETTING: A major out-patient tuberculosis clinic in Nairobi, Kenya. OBJECTIVE: To
      ascertain the cost-effectiveness of the polymerase chain reaction (PCR) for the
      diagnosis of tuberculosis in an urban setting in a developing country. DESIGN: A
      cost-effectiveness analysis of PCR and direct smear microscopy examination based
      on theoretical modelling. The cost-effectiveness was expressed in costs per
      correctly diagnosed tuberculosis patient for each of the two diagnostic
      techniques. Data were obtained from the literature, from the staff and the
      register at the health facility and from structured interviews with patients.
      Assumptions were made when no data were available. RESULTS: The PCR is expected
      to be more specific and sensitive than the routine procedure for diagnosis, but
      it is also more costly. The routine procedure based on direct smear microscopy
      turned out to be 1.8 times as cost-effective as PCR. CONCLUSION: It is concluded
      that the PCR method can potentially be a cost-effective screening procedure for
      tuberculosis, provided that the largest contributing cost component, the costs of
      the PCR-kit, can be reduced substantially.

PMID- 9526198
TI  - Use of IS901 and IS1245 in RFLP typing of Mycobacterium avium complex:
      relatedness among serovar reference strains, human and animal isolates.
AB  - SETTING: Mycobacterium avium complex (MAC) includes major acquired immune
      deficiency syndrome (AIDS)-associated pathogens. Formerly, MAC serotyping was
      used for epidemiological purposes. Recently, restriction fragment length
      polymorphism (RFLP) typing has become available. OBJECTIVE: Examination of the
      usefulness of insertion sequence IS1245 in RFLP typing of MAC isolates and the
      association with IS901 RFLP. DESIGN: Ninety-four serovar reference strains were
      compared with 144 clinical and animal MAC isolates in RFLP typing. RESULTS: All
      but four strains containing M. avium-specific-rRNA possessed IS1245. Most human
      isolates showed polymorphic multiband IS1245 patterns, which were associated with
      serovars 4, 6 and 8. Sequential clinical isolates obtained at up to five years'
      distance displayed indistinguishable/closely related patterns. Eleven M.
      paratuberculosis isolates showed indistinguishable six-band patterns. All 29 MAC
      isolates from 23 bird species, 7/23 from mammals and 1/81 clinical isolates
      showed an IS1245 three-band pattern, associated with serovars 1, 2 and 3. All
      these IS1245 'bird' type strains showed closely related IS901 RFLPs. Only three
      IS1245 'non-bird' type strains contained IS901, but exhibited completely
      different RFLP patterns. CONCLUSION: IS1245-RFLP typing is useful for the
      classification of M. avium and epidemiology of most human isolates. The highly
      conserved IS901 and IS1245 RFLPs among 'bird' type isolates provide proof that
      these strains constitute a separate taxon within the MAC.

PMID- 9526199
TI  - Expenditure and loss of income incurred by tuberculosis patients before reaching
      effective treatment in Bangladesh.
AB  - This small study undertook to assess the economic consequences of developing
      tuberculosis (TB) among patients presenting to the TB clinic run by the Danish
      Bangladesh Leprosy Mission in NW Bangladesh. The loss of income resulting from
      the illness, and the actual expenditure incurred by medicines and doctor's fees
      before registration for treatment, were estimated and totalled for 21 patients
      serially registered at the clinic. The results showed a mean financial loss to
      the patient of US$ 245-an exorbitant sum for a village Bangladeshi. Perhaps
      economic deprivation suffered by TB patients could be used as a measure of
      success of the programme.

PMID- 9526200
TI  - Tuberculous meningitis in a five-week-old infant.
AB  - We present the case of a five-week-old infant with tuberculous meningitis. The
      contact investigation and a review of the literature helped us differentiate
      congenital from acquired tuberculous meningitis. Though rare, we with to
      emphasize the importance of considering tuberculosis in any neonate with
      meningitis that fails to respond to conventional treatment, particularly in
      infants living in an environment where tuberculosis is prevalent.

PMID- 9526201
TI  - A resected case of Mycobacterium szulgai pulmonary disease.
AB  - We present the first reported case of Mycobacterium szulgai pulmonary disease
      that needed surgical resection due to unsuccessful antimycobacterial
      chemotherapy. The patient was a non-immunocompromised 48-year-old male who
      presented with hemoptysis and whose sputum cultures repeatedly yielded M.
      szulgai. Antimycobacterial chemotherapy with isoniazid (INH) and rifampin
      (RMP)/ethambutol (EMB) for three years had been unsuccessful, and subsequent
      chemotherapy with RMP, EMB, ethionamide and kanamycin had to be discontinued due
      to liver dysfunction. Surgical resection was finally performed, and resulted in a
      favorable outcome. Although M. szulgai pulmonary disease is usually well
      controlled by antimycobacterial chemotherapy alone, surgical treatment may be
      necessary in some cases.

PMID- 9526202
TI  - CD4+ T-lymphocytopenia in pulmonary tuberculosis.

PMID- 9526203
TI  - All change is not progress.

PMID- 9526204
TI  - Long-term results of cemented Charnley low-friction arthroplasty in patients aged
      less than 30 years.
AB  - The results of cemented Charnley low-friction arthroplasty in patients aged less
      than 30 years are presented. Eighty-three arthroplasties were performed on 55
      patients with an average age of 24.9 years (range, 17-29 years) and an average
      follow-up period of 240 months (20 years; range, 62-360 months). There were 2
      nonfatal pulmonary emboli, 2 cases of deep sepsis, and 3 fractured femoral
      implants. Twenty-eight acetabular components migrated (34%), 25 have been revised
      (30%), and the average annual acetabular wear rate was 0.12 mm. Sixteen femoral
      implants subsided (19%), and fracture of the tip of the cement mantle occurred in
      8 hips (10%). Nineteen femoral components (23%) were revised; femoral osteolysis
      was seen in 15 hips (18%) and changes in the calcar in 33 (38%). Acetabular
      component survivorship was 92% (95% confidence interval, 85-98%) at 10 years, 70%
      (60-81%) at 20 years, and 68% (57-79%) at 25 years, with the figures for the
      femoral implant being 93% (87-98%), 76% (66-86%), and 73% (62-85%), respectively.

PMID- 9526205
TI  - Wear and fracture of the acetabular cup in Charnley low-friction arthroplasty.
AB  - Seven cases of progressive wear-out and fracture of the cemented high-density
      polyethylene cup in Charnley low-friction arthroplasty were identified in a group
      of 1,815 revisions of failed total hip arthroplasties. Normal function, rapid
      wear in the superolateral direction, and localized superolateral loss of bone
      cement interface support with perfect medial cup fixation but, above all,
      asymptomatic nature of the problem until the moment of sudden failure were the
      characteristic features. The time to failure ranged from 11 to 20 years. Stem
      fixation remained unaffected. The findings suggest that the problem was wear-out
      without any changes that could have been attributed to the volume of high-density
      wear particles shed into the tissues.

PMID- 9526206
TI  - Posterior cruciate ligament-sparing versus posterior cruciate ligament
      sacrificing arthroplasty. Functional results using the same prosthesis.
AB  - The functional outcomes of 143 total knee arthroplasties performed by 1 surgeon
      between 1988 and 1992 were reviewed. Ninety-three procedures were carried out
      with sacrifice of the posterior cruciate ligament (PCL); in 50, the PCL was
      preserved. All cases were performed using the Kinemax prosthesis (Howmedica,
      Rutherford, NJ). Demographically, there were no differences between the 2 patient
      groups. Patients were evaluated over a mean follow-up period of 3 years (range, 2
      6 years) using the 100-point Hospital for Special Surgery knee scoring system.
      The data revealed no difference in clinical or early radiographic outcome between
      PCL-sacrificing and PCL-retaining arthroplasties and support the argument that
      PCL sacrifice should be considered in cases in which extensive releases and
      complex ligamentous balancing are required.

PMID- 9526207
TI  - Total knee arthroplasty kinematics. Computer simulation and intraoperative
      evaluation.
AB  - The goal of this work was to develop computer simulations for intraoperative
      testing of the passive kinematics of knee prostheses. These are based on an
      anatomic model of the reconstructed joint, represented in the sagittal plane. A
      femoral component and a tibial component are linked by 3 springs that model the
      relevant ligaments, with the posterior cruciate providing the primary constraint.
      The components' behavior at each flexion angle is obtained by minimizing the
      total strain energy stored in the ligaments. Simulations were performed in vivo
      on 10 Interax implants (Howmedica International, Stain, UK) and showed good
      agreement with intraoperative observations, allowing monitoring of new parameters
      such as contact point motion, ligament strains, and the energetic state of the
      knee. This work contributes to the comprehension of individual knee kinematics
      after total knee arthroplasty, to improve long-term results and standardize the
      evaluation of the results of joint restoration.

PMID- 9526208
TI  - Drainage versus nondrainage in simultaneous bilateral total hip arthroplasties.
AB  - A prospective study of 48 patients (96 hips) who had undergone primary
      simultaneous bilateral total hip arthroplasty was conducted to assess the effect
      of postoperative suction drainage on wound healing and infection. A suction drain
      was placed by randomization of the drained versus undrained side. The same
      surgical technique was used in all total hip arthroplasty wounds. Statistical
      analysis of the results showed significant differences with respect to drainage
      from the wound, soaked dressings requiring reinforcements, ecchymosis, and
      erythema about the wound in the group without drainage. There was no specific
      correlation between the incidence of wound complications and infection after
      total hip arthroplasty and the use or nonuse of closed-suction drainage. The hip
      score and range of motion of the hip were unaffected by the use or nonuse of the
      drains. The cost of 1 set of hemovac drains is $135 and the cost for 4-5
      dressings and bed sheet changes is about $50. Although the hemovac is more
      expensive, the authors recommend the routine use of suction drains for wounds
      after primary total hip arthroplasty to reduce drainage, soaked dressings
      requiring reinforcement, ecchymosis and erythema around the wound, and
      psychological impact on the patient's fear of bleeding.

PMID- 9526209
TI  - Conservative treatment of femoral shaft fractures in patients with total hip
      arthroplasty.
AB  - Over a period of 20 years, 34 patients with a total hip arthroplasty were treated
      conservatively for a femoral shaft fracture. Thirty-five fractures were treated
      by traction followed by cast-brace or by cast-brace alone. Sound healing was
      obtained in 33 fractures. Problems were angular malalignment jeopardizing
      revision surgery in cases of loosening, long hospitalization, and a considerable
      complication rate. As a consequence, the authors no longer recommend conservative
      treatment as the first choice for these difficult fractures.

PMID- 9526210
TI  - Cost comparison between bilateral simultaneous, staged, and unilateral total
      joint arthroplasty.
AB  - A hospital-based computer system was used to compare the inpatient costs of
      performing bilateral simultaneous sequential, staged, and unilateral total hip
      and knee arthroplasties. Bilateral simultaneous sequential total knee
      arthroplasty was 36% less costly than 2 unilateral total knee arthroplasties.
      Bilateral simultaneous sequential total hip arthroplasty saved 25% over the costs
      of performing 2 unilateral hip arthroplasties. Prosthetic costs range between 28%
      and 43% of the total costs of hospitalization. There was a significant
      correlation between hospital length of stay, morbidity, and total costs, but no
      correlation with patient age and sex except in the unilateral knee patients.
      Bilateral simultaneous sequential joint arthroplasty can save more than $10,000
      for each total knee patient and more than $8,000 for each total hip patient.

PMID- 9526211
TI  - Low-molecular-weight heparin and partial thromboplastin time-adjusted
      unfractionated heparin in thromboprophylaxis after total knee and total hip
      arthroplasty.
AB  - Thromboprophylaxis with heparins after total hip arthroplasty (THA) and total
      knee arthroplasty (TKA) is well established. The aim of this study was to compare
      low-molecular-weight heparin (enoxaparin) with partial thromboplastin time (PTT)
      adjusted, unfractionated heparin (heparin sodium). In a prospective study of THA
      and TKA 246 patients, physical examination and compression and duplex ultrasound
      were performed 1 day before and 7 and 14 days after surgery. One hundred thirty
      patients received 40 mg enoxaparin subcutaneously once per day. One hundred
      sixteen patients received 5,000 IU heparin sodium subcutaneously 3 times daily.
      As the PTT did not reach 40 seconds, the heparin sodium dosage was increased to
      7,500 IU 3 times daily. The overall thrombosis rate was 4% (n = 10). In the
      enoxaparin group, the rate was 2.9% of the 70 THAs and 10% of the 60 TKAs.
      Thrombosis also occurred in the group that received heparin sodium: 1.8% of the
      THAs and 1.7% of the TKAs. For TKA, the difference between the 2 heparin groups
      was statistically significant. In the thromboprophylaxis of TKA, PTT-adjusted
      unfractionated heparins are superior to fixed doses of low-molecular-weight
      heparins.

PMID- 9526212
TI  - Factors affecting length of stay and need for rehabilitation after hip and knee
      arthroplasty.
AB  - The purpose of this study was to determine the factors that predict the length of
      stay on a surgical service after total hip or knee arthroplasty and the factors
      that predict whether a patient will require admission to a rehabilitation unit
      before he or she is ready to return home. The authors reviewed the records of all
      patients admitted to the Albany Medical Center for elective total hip or total
      knee arthroplasty in 1995. The study looked for correlations of patients' age,
      sex, marital status, body mass index, and comorbid illnesses with length of stay
      on the surgical service and need for inpatient rehabilitation. The only factor
      that correlated with length of stay on the surgical unit was age. The factors
      that correlated with the need for inpatient rehabilitation were age and diabetes
      mellitus.

PMID- 9526213
TI  - Revision of unicompartmental arthroplasty of the knee. Clinical and technical
      considerations.
AB  - In 73 unicompartmental arthroplasties of the knee that were revised, the major
      causes of failure were progression of arthritis and implant failure. The interval
      between the primary and revision averaged 56 months. Eighty-eight percent were
      revised to a variety of total condylar prostheses. Bone loss was classified by
      defect at the end of preparation. In 31 patients, there were none; in 17, the
      defect was in either the femur or the tibia; and in 25, there were defects in
      both the femur and the tibia. Forty-seven of these defects were small and
      contained, presenting little problem. Twenty defects were either large,
      contained, or peripheral, requiring reconstruction. Fifteen knees were lost as a
      result of death (but there had been satisfactory knee function); 2 were lost to
      follow-up evaluation, and 3 have required further revision. Seventy-nine percent
      of the surviving knees had excellent or good knee function at an average follow
      up period of 56 months.

PMID- 9526214
TI  - An intramedullary cement spacer in total hip arthroplasty .
AB  - Revision arthroplasty of the hip is often complicated by infection, bone loss,
      and perioperative fracture of the femur. A simple, inexpensive spacer that keeps
      tissue planes intact and prevents soft tissue contracture during the
      interoperative period of a 2-stage revision is described. This can provide
      intramedullary support to a fractured or weak femur and enable local antibiotic
      delivery, as well as permit limited mobilization of the patient. It can be easily
      fabricated during surgery using universally available materials and can be
      tailored for specific requirements. Such a spacer was used in 5 cases. The
      experience is presented, and the technique and pitfalls are discussed.

PMID- 9526215
TI  - An in vitro study of a new design of acetabular cement pressurizer.
AB  - Aseptic loosening of the acetabular component remains one of the limiting factors
      in the long-term success of total hip arthroplasty. Cement pressurization has
      been shown to improve fixation. A new pressurizer has been designed that seals
      around the rim of the acetabulum and covers the transverse ligament notch with a
      flap. The results of in vitro testing of this device are presented and compared
      with those of pressure generated by insertion of an acetabular cup. The
      pressurizer allowed sustained, uniform cement pressurization. Peak pressures with
      the new pressurizer were 180 kPa at both the iliac region of the rim and the pole
      of an instrumented model acetabulum, compared with 55 kPa at the rim and 120 kPa
      at the pole on cup insertion. Pressures were maintained in the range of 80-90
      kPa. The flap was effective in preventing cement leakage from the notch, and
      pressures were higher than when the flap was absent. Cup insertion alone gave
      only transient pressurization, substantially less near the rim of the acetabulum
      than at the pole. Peripheral pressurization may be significant in producing
      secure local fixation at the rim of the acetabulum, in particular in the region
      of the ilium (Charnley zone 1), where radiolucencies are most commonly observed
      and where stresses in the implanted acetabulum are highest. Improved rim fixation
      may also play a role in preventing the ingress of wear debris.

PMID- 9526217
TI  - Vascular injuries in total knee arthroplasty. A review of the problem with
      special reference to the possible effects of the tourniquet.
AB  - Considering the proximity of the major vascular structures to the back of the
      knee, vascular complications of total knee arthroplasty are relatively rare. A
      patient who developed acute vascular insufficiency immediately following a total
      knee arthroplasty is reported. This stimulated a survey of arterial complications
      encountered by members of the British Association for the Surgery of the Knee.
      The majority of surgeons still use a tourniquet but will modify their practice if
      there is anxiety about vascular status. The mechanism of injury to the vascular
      system is either direct trauma or thrombosis. The outcome following treatment
      after direct injury is extremely good. The outcome after thrombosis is extremely
      poor. There is no recorded case of thrombosis occurring when a tourniquet was not
      used. Whether all knee arthroplasties should be done without a tourniquet is
      discussed. Early intervention is vital if a vascular injury is suspected.

PMID- 9526216
TI  - Factor V Leiden and the risk of proximal venous thrombosis after total hip
      arthroplasty.
AB  - Deep vein thrombosis (DVT) remains a major cause of morbidity in patients
      undergoing total hip arthroplasty (THA). Despite postoperative DVT prophylaxis,
      20-50% of THA patients still develop DVT. Currently, there is no accurate way of
      predicting which patients will develop DVT despite standard prophylaxis. The
      presence of factor V Leiden is the most common cause of inherited DVT risk. It
      has been postulated that patients who have factor V Leiden and are subjected to
      thrombogenic stressors such as THA would have an increased risk of thrombosis.
      The factor V Leiden genotype of 36 patients who developed proximal DVT after
      surgery and 45 control patients who had THA but did not develop DVT was
      determined. All patients had had prophylaxis against thrombosis using
      intermittent pneumatic compression alone or in combination with warfarin or
      aspirin. Surveillance for proximal DVT was performed on all patients prior to
      discharge by duplex ultrasound. The 2 groups were similar in age, sex, and type
      of operation. Three of 36 study patients who had developed DVT (8%) and 2 of 45
      control patients who had not developed DVT (4%) were heterozygotes for factor V
      Leiden; these prevalences were not statistically different. Heterozygosity for
      factor V Leiden is not associated with DVT prophylaxis failure in patients
      undergoing THA.

PMID- 9526218
TI  - Bilateral pathologic fractures in a patient with beta-thalassemia undergoing
      total hip arthroplasty.
AB  - A 49-year-old woman with beta-thalassemia minor and degenerative joint disease
      underwent bilateral hybrid total hip arthroplasty. Postoperative radiographs
      showed bilateral femoral shaft fractures extending distal to the cement plug.
      Examples of the hemodynamic complications of beta-thalassemia have been reported
      in the literature; however, this particular orthopaedic complication has not been
      reported before.

PMID- 9526219
TI  - Dental compression syndrome: bruxing, TMJ, occlusal equilibration and full arch
      reconstruction.

PMID- 9526220
TI  - Management of the stroke patient. 1994 Ishmael Essay Award.

PMID- 9526222
TI  - Retention: 10 ways to prevent patients from falling through the cracks.

PMID- 9526221
TI  - Is it really magic? Laser use in scaling and root planing.

PMID- 9526223
TI  - Case report: single implant/allograft.

PMID- 9526224
TI  - Variations in the size and location of the mental foramen.

PMID- 9526225
TI  - IMTEC implants: clinical evaluation of 120 patients: 548 implants.

PMID- 9526226
TI  - Are surgical face masks a false sense of security?

PMID- 9526227
TI  - Titanium and osteointegration--preliminary study.

PMID- 9526228
TI  - The ingredients of a successful snuff cessation program.
AB  - From the brief outline of the details so necessary for a successful snuff
      cessation program, it is apparent that snuff addiction is a complex and difficult
      issue. In the same way that some things in clinical dentistry you prefer to do
      and some things you prefer to refer, so it may be for your snuff addicts. By
      virtue of your rapport with your patient, you may be the best to treat the
      patient's addiction or you may want to refer the patient to an established snuff
      cessation program (not a cigarette cessation program). Simply telling the snuff
      addict not to dip is grossly inadequate. Dentists have been very successful in
      stemming the tide of dental caries and periodontal disease. From the knowledge
      gained in these prevention programs and the fact that snuff has such an impact in
      the mouth, the dentist is the natural health care provider to conduct successful
      snuff cessation programs.

PMID- 9526229
TI  - Endodontic implications of anatomical variations and developmental anomalies in
      maxillary and mandibular anterior teeth.
AB  - Endodontic treatment of maxillary and mandibular anteriors does not generally
      offer strenuous challenges to the skilled practitioner. Most cases are relatively
      straightforward and can be treated without complication. Anatomical and
      developmental variations do exist in these teeth, however, which can add an
      enormous degree of technical complexity, and even doom endodontic treatment to
      failure. The prudent clinician must be aware of these variations, modify
      treatment procedures accordingly, and inform the patient of these possible causes
      of treatment failure.

PMID- 9526230
TI  - Management of traumatized permanent incisor teeth with horizontal root fractures.
AB  - Proper management of permanent incisors with horizontal root fractures includes
      careful diagnosis, continued re-evaluation and a conservative treatment approach.
      The location of the root fracture and pulpal vitality status both play important
      roles in proper treatment decisions. A thorough examination, judicious treatment
      and follow-up on the part of both dentist and patient can result in long term
      retention of many of these traumatized teeth.

PMID- 9526231
TI  - Trends in dental computerization in Oklahoma practices.

PMID- 9526232
TI  - Six ways to maximize a healthcare financing program.
AB  - There are six proven ways to integrate a healthcare financing program into your
      practice. Challenge yourself to maximize your financial service. You will see
      more people receive valuable care. You will grow your practice. You will reap
      financial reward. You will provide more of the quality dentistry that makes the
      art and science of your profession a joy.

PMID- 9526233
TI  - Implant diagnostics utilizing computed tomography imaging.

PMID- 9526235
TI  - A new way to help patients floss.

PMID- 9526234
TI  - Endodontic implications of the variability of the root canal systems of posterior
      teeth.
AB  - Variations in the morphology of roots and root canal systems create challenges
      which the dental practitioner must be able to recognize. Endodontic therapy is
      predictable and successful only to the extent that the root canal system can be
      debrided, disinfected and sealed against future contamination. In order to
      accomplish these goals it is necessary to become familiar with the variability of
      the system we seek to treat.

PMID- 9526237
TI  - Epidemiology, etiologies and treatment of cleft lip and cleft palate.

PMID- 9526236
TI  - Detection of HIV proviral DNA on toothbrushes: a preliminary study.

PMID- 9526238
TI  - Special considerations ... for the dental professional for patients with Down's
      syndrome.

PMID- 9526239
TI  - Periodontal disease associated with insulin-dependent diabetes mellitus.

PMID- 9526240
TI  - Some caveats on ... dental practice sale advisors.

PMID- 9526242
TI  - The toothbrush, Kaposi's sarcoma and AIDS: a case demonstrating interesting
      associations.

PMID- 9526241
TI  - Nightguard vital bleaching (NGVB).

PMID- 9526243
TI  - Stress, professional burnout and dentistry.
AB  - Dentistry is a profession which is subject to a wide range of stressors which can
      lead to professional burnout. The dentist should be aware of these stressors and
      attempt to manage them in order to avoid becoming occupationally dissatisfied.
      Economic factors including the cost of a dental education and the start up costs
      of a practice can seem overwhelming if they are not considered as an investment
      in the professional future of the practitioner. Debt reduction and income goals
      should be set and periodically re-evaluated to keep the costs of entering and
      conducting business in perspective. The professional image or status of dentistry
      as a health care profession can cause stress to some practitioners. This is
      particularly true of dentists who feel compelled to practice in a less than
      desirable environment and those who feel professionally isolated. Active
      membership in local, state and national organizations can lessen the feelings of
      professional isolation and can provide contacts who can help starting
      practitioners improve their practice environments. Patient interactions can
      induce a great deal of stress in any health care provider. This is an individual
      response and must be countered in an individualized manner. Frequent breaks and
      relaxation exercises can reduce this type of stress.

PMID- 9526244
TI  - Assessment of temporomandibular injury and orofacial pain.
AB  - Every individual has physical faults which makes him less than a perfect
      biological specimen. This is the foundation for the legal "eggshell principal."
      Most of us do not have perfect skeletal formation, muscular adaptation,
      neurological or vascular systems. Additionally, we may not have complete symmetry
      and ideal form to our cranium or mandible. Our dentitions are imperfect. All of
      these imperfections play a role in every injury. The variances of normal that are
      seen in any medical or dental population, must be accepted; therefore, a given
      injury can have tremendously varied sequelae, depending on the person receiving
      it. The patho-physiology resultant from an accident may not parallel the severity
      of the motor vehicle accident, fall or blow. Prompt and proper evaluation of the
      individual-turned-patient is imperative. Referral to a dentist, competent in
      providing the necessary evaluation of the injury, is the responsibility of those
      individuals attending to the injured person's physical, emotional, and financial
      trauma. Their physician, dentist, attorney or counselor should take the
      responsibility of providing proper referral. The four most dangerous words in
      medicine and dentistry today are: "It Will Go Away." People often develop serious
      sequelae by assuming that their problem will "go away" by just leaving it alone
      long enough or by simply ignoring it. With proper evaluation and management, most
      trauma related temporomandibular injuries can be corrected or at least be
      properly managed.

PMID- 9526245
TI  - Microbiological contamination of dental unit water lines.

PMID- 9526246
TI  - The fears and facts of reporting child abuse.

PMID- 9526247
TI  - Fluoride: surprising factors in bottled water.

PMID- 9526248
TI  - Hygiene employment prospects in Pennsylvania.

PMID- 9526249
TI  - Maximum marketing for minimum dollars.

PMID- 9526250
TI  - National Museum of Dentistry opens.

PMID- 9526251
TI  - Oral manifestations in HIV-infected children.

PMID- 9526252
TI  - Give teeth a sporting chance.

PMID- 9526253
TI  - Preventing mouth injuries during sports.

PMID- 9526254
TI  - Breaking the link between snuff and athletes.

PMID- 9526255
TI  - Dental implications of smokeless tobacco use.

PMID- 9526257
TI  - Thermal activated plastic sterilization: a technical description.

PMID- 9526256
TI  - Dentistry and the environment. Medical waste: a Society for Hospital Epidemiology
      of America (SHEA) position paper.

PMID- 9526258
TI  - Radiation safety and dentistry.

PMID- 9526259
TI  - Making your office accessible to the disabled.

PMID- 9526260
TI  - Addressing the needs of cancer patients. Before, during and after chemotherapy
      and radiation therapy.

PMID- 9526261
TI  - The changing face of geriatric dental care.
AB  - Just because a patient has reached a certain age does not necessarily mean he or
      she requires specific treatments. This will vary depending upon the patient's
      general history, his or her oral hygiene, general health and diet. It is
      important to avoid stereotyping seniors: they all have different medical
      backgrounds, different lifestyles and different needs.

PMID- 9526262
TI  - An investigation of antibiotic prescribing by general dental practitioners: a
      pilot study.
AB  - PURPOSE OF STUDY: This pilot study was designed to investigate how general dental
      practitioners prescribe antibiotics. METHODS: A total of 200 prescriptions were
      selected at random from 1775 prescriptions dispensed in 55 pharmacies across a
      Liverpool district. The type of antibiotic prescribed, the duration, frequency
      and dose were analysed. The legibility and any other errors or omissions were
      also noted. RESULTS: The legibility of the prescriptions was good with very few
      errors or omissions from the patient details. Seven different types of
      antibiotics were used with amoxycillin being the most frequently prescribed
      (64.5%), followed by metronidazole (21.5%). Penicillin, erythromycin,
      clindamycin, tetracycline and cephradine were the other antibiotics prescribed.
      There was a wide variation in the duration, frequency and doses prescribed.
      CONCLUSION: The results of this pilot study show that many practitioners
      prescribe antibiotics for inappropriately long periods and with inconsistent
      frequency and duration.

PMID- 9526263
TI  - Biocompatibility of dentine-bonding agents. 1. Factors associated with function.
AB  - The paper reviews the literature on the biocompatibility of dentine-bonding
      agents with respect to their ability to perform their defined function. Scanning
      electron microscope (SEM) pictures, prepared by the critical-point drying
      technique, are used to illustrate the various aspects of bonding to dentine such
      as the nature of dentine, the smear layer and the effects of primers,
      conditioners and etchants. From the review of the literature it can be concluded
      that the mechanisms of bonding to dentine are still not fully understood. The
      more recently introduced materials use mechanical means of adhesion where the
      dentine is altered by primers or conditioners to expose collagen fibres and a
      hybrid zone is created by the penetration of unfilled resins into this fibrous
      network. The irritant effects of a bonding agent on pulpal tissue may be caused
      by bacterial ingrowth due to initial poor bonding or a breakdown of the bond in
      addition to any inherent toxicity of the constituents of the bonding agent.

PMID- 9526264
TI  - The MGDS examination: a systematic approach. 1. General preparation and Part I of
      the examination. Member in General Dental Surgery.
AB  - This paper is the first in a series of four which present a systematic approach
      to colleagues who are preparing for and sitting the examination for the Diploma
      of Membership in General Dental Surgery (MGDS) of The Royal College of Surgeons
      of England. Although some details may differ, the general principles set out in
      the four papers apply equally to the MGDS examinations of the other Royal
      Surgical Colleges.

PMID- 9526265
TI  - The relationship between Universal Dental Anchorage System (UDA) pins and the
      dental pulp chamber, in vitro.
AB  - PURPOSE OF STUDY: The Universal Dental Anchorage (UDA) System incorporates the
      use of pins inserted into enamel and dentine to retain a pontic. The pins are
      placed horizontally into teeth in the region of the contact area and so are
      potentially placed close to the dental pulp. This study aims to investigate and
      measure this relationship to assess if the pulp may be placed at risk during pin
      hole preparation or UDA pin placement. METHODS: Teeth were assessed
      radiographically and pins placed according to manufacturer's instructions. The
      teeth were subsequently sectioned through the pin position and measurements from
      the pin tip to the pulp chamber made at 4X magnification. RESULTS: In the
      majority of the teeth the pins were in close proximity to the pulp chamber (mean
      +/- sd = 0.8 +/- 0.7 mm). Two pins were in direct communication with the pulp
      chamber. Seven pins were separated from the pulp chamber by only 0.1-0.5 mm and
      six pins by 0.6-1.0 mm. Three pins were more than 1.0 mm from the pulp chamber.
      CONCLUSION: The results suggest that the use of 2.1 mm UDA pins would, in many
      cases, represent a risk to pulpal health.

PMID- 9526266
TI  - Sharps injuries in dental practice.
AB  - Sharps injuries are common in dental practice and may allow transmission of blood
      borne viruses. The transmission rates of hepatitis B (HBV) to non-vaccinated
      recipients, hepatitis C (HCV) and human immunodeficiency virus (HIV) after a
      needlestick injury are 6-30%, 2.7-10% and 0.1-0.3% respectively. Five strategies
      to prevent percutaneous injuries in dental surgeries are considered: a universal
      level of infection-control, surgery design, working practices, glove use and
      vaccinations. First-aid for sharps injuries and post-exposure management of those
      involving sources with HBV and HIV are described. Anticipation, planning and
      training can reduce the incidence of injuries and minimise their impact.

PMID- 9526267
TI  - Clinical effectiveness and primary dental care. 2. The influence of health
      economics.
AB  - The first paper gave an overview of the issues concerning clinical effectiveness
      and primary dental care. However, the rise of evidence-based health care has the
      potential to increase as well as control costs. With the demands on health care
      ever increasing, the costs of interventions as well as their benefits must be
      assessed concurrently. This is the area covered by the science of health
      economics, which will play an increasing role throughout all health services as
      an aid to prioritising the deployment of resources. It is inevitable, therefore,
      that the theories and methods of health economics will affect the delivery of
      primary dental care in the future.

PMID- 9526269
TI  - Selective periapical radiology compared to panoramic screening.
AB  - PURPOSE OF STUDY: To assess whether selected periapical radiographs, taken
      according to High Yield Criteria, can reveal as much intra-osseous pathology as
      universal panoramic screening. POPULATION STUDIED: The records of 1101 RAF
      recruits enlisted in 1988-89, average age 19 years (range 16-26). METHODS: The
      clinical records and bitewing radiographs of the recruits were examined and the
      requirement for periapical radiographs determined according to high yield
      criteria. A template, cut out to simulate the area covered by a periapical
      bitewing radiograph, was placed over the suspect region on the panoramic film and
      any findings found within the template recorded. The entire dental panoramic
      tomograph was then examined on a masked screen under 2X magnification and any
      further findings recorded. FINDINGS: There was a considerable number of findings
      reported, including three large isolated radiolucent areas, 75 periradicular
      radiolucent areas, four probable cysts and 1187 unerupted mandibular third
      molars. However, when the clinical significance of these 'lesions' was assessed
      only those related to dental causes appeared to have significant clinical
      implications and the results indicated that these could have been detected by
      selective radiology. CONCLUSION: This study showed that the only pathology which
      occurs frequently enough to justify radiographic screening of the jaws in young
      adults is related to teeth. It seems probable that this type of pathology can be
      at least as well detected by selective periapical screening, using high yield
      criteria, as is possible by universal panoramic screening.

PMID- 9526268
TI  - Effectiveness of light-curing units in vocational training practices. A project
      administered by the Research Committee of the Faculty of General Dental
      Practitioners (UK).
AB  - A project has been organised by the Research Committee of the Faculty of General
      Dental Practitioners (UK) in conjunction with vocational training advisers in
      which vocational dental practitioners (VDPs) tested the effectiveness of the
      light-curing units in their surgeries using Heliotests (Ivoclar-Vivadent) and
      Z100 Composite (3M). The VDPs also completed a questionnaire giving details of
      their light-curing units. The mean incremental depth stated as being used by the
      respondents was 2.6 mm; 43.5% of the participants' light-curing units (n = 63)
      were found to produce a depth of cure less than this figure. However, no
      correlation was found between reported post-operative clinical problems and cure
      depth lower than 2.6 mm. A negative correlation between depth of cure and age of
      light-curing unit was noted, with older units tending to cure the composite
      samples to less depth than newer units (p = 0.002). One-fifth of the
      participating VDPs' practices had some means of checking curing-light
      effectiveness. Greater awareness of the need to monitor practice light-curing
      units is therefore required.

PMID- 9526270
TI  - Home relines and residual ridge resorption.
AB  - Two cases of patients who have relined their complete dentures with home-applied
      materials in an attempt to improve the denture stability are discussed. The
      resultant damage to the residual tissues is described. A review of the literature
      on the effects of home relines leads to suggestions for the regular review of
      patients who wear complete dentures.

PMID- 9526271
TI  - MGDS log diary: the reorganised occlusion. Member in General Dental Surgery.
AB  - This article describes the restorative treatment of a 49-year-old woman whose
      lower anterior teeth had over-erupted, reducing the space available for a
      denture. Areas of the acrylic resin had fractured off her upper cobalt/chromium
      denture. The treatment plan and a variety of the treatment planning options are
      discussed. The initial treatment provided included an upper bite-raising
      appliance and routine periodontal and restorative treatment. This was followed by
      full coronal coverage of 6, 4 and 6 incorporating rest seat preparations and
      guide planes and the provision of the definitive cobalt/chromium overdenture. The
      article concludes with a discussion of the aims, objectives and prognosis of the
      treatment provided.

PMID- 9526272
TI  - Diagnosis and treatment of the cracked tooth.
AB  - This review paper discusses the recognised factors which predispose to cracked
      tooth syndrome. In addition, common presenting symptoms and the various methods
      to aid clinical diagnosis of this problem are examined. The incidence of the
      condition is reported and the prognosis of the various forms of fracture, as
      suggested by clinical presentation, are outlined with reference to the available
      literature. Benefits and relative demerits of traditional and more modern
      treatment options are presented and recommendations made for future research.

PMID- 9526273
TI  - Mandibular supernumerary premolars: orthodontic and surgical considerations.
AB  - The presence of mandibular supernumerary premolars in two patients is reported.
      These teeth were discovered from panoramic oral radiographs during routine
      orthodontic assessment. The specific location of these teeth has a strong
      implication in the management of these cases. In the two cases reported, surgical
      removal is required prior to orthodontic treatment. A discussion is also made for
      the identification, location and surgical removal of these supernumerary teeth.

PMID- 9526274
TI  - Reproductive and developmental hazards. An overview for occupational and
      environmental health nurses. Agency for Toxic Substance and Disease Registry.

PMID- 9526276
TI  - Employee health services integration: meeting the challenge. Successful program.
AB  - 1. The first step of a successful Employee Health Service integration is to have
      a plan supported by management. The plan must be presented to the employees prior
      to implementation in a "user friendly" manner. 2. Prior to computerization of
      employee health records, a record order system must be developed to prevent
      duplication and to enhance organization. 3. Consistency of services offered must
      be maintained. Each employee must have the opportunity to receive the same
      service. Complexity of services will determine the site of delivery. 4.
      Integration is a new and challenging development for the health care field.
      Flexibility and brainstorming are necessary in an attempt to meet both employee
      and employer needs.

PMID- 9526275
TI  - Noise induced hearing loss among male airport workers in Korea.
AB  - The purposes of this study of airport workers were to a) determine the prevalence
      and symptoms of hearing loss, and b) identify compliance in using hearing
      protective devices (HPDs) and its relationship with hearing loss. This cross
      sectional epidemiological study was conducted with 255 noise exposed and 195 non
      noise exposed, full time, male workers at a large metropolitan airport in Seoul,
      Korea. The three measures used were the self administered Occupational Hearing
      Questionnaire (OHQ), an audiological assessment, and a record review of baseline
      hearing and noise levels of locations in which the employee worked. The results
      showed a significant difference in prevalence of hearing loss (more than 25dB)
      between the noise and the non-noise exposed groups (p < .05). About 60.8% of
      noise exposed workers reported continuous use of the HPDs. The continuous HPD
      users had significantly lower rates of hearing loss than the occasional users or
      non-users. The major symptom for workers with low frequency hearing loss was
      trouble in communication, whereas tinnitus and fullness in the ear were the most
      common symptoms for the workers with high frequency hearing loss. The airport
      workers exposed to excessive noise had a great deal of high frequency hearing
      loss. The degree of hearing loss present reinforces the need for aggressive
      hearing conservation programs among airport workers exposed to noise.

PMID- 9526277
TI  - Critical thinking. A framework for problem solving in the occupational setting.
AB  - 1. Critical thinking is essential in providing quality nursing care.
      Understanding the process of critical thinking increases the nurse's efficiency
      in the skill of problem solving. 2. To employ the critical thinking process, the
      nurse must analyze and criticize a problematic or change situation, reason, make
      inferences, and reach conclusions. 3. The result of critical thinking is
      attaining goals, solving problems, and making decisions. 4. Critical thinking is
      a process and not an outcome.

PMID- 9526279
TI  - Project management, Part II.

PMID- 9526278
TI  - Management of latex reactions in the occupational setting.
AB  - 1. The increased use of natural rubber latex barrier protection to prevent
      exposure to bloodborne pathogens has led to an increase in latex related health
      reactions, particularly associated with glove use. 2. The three types of
      reactions to latex in order of frequency include irritant contact dermatitis,
      allergic contact dermatitis, and immediate systemic/anaphylaxis reactions. 3. The
      management goal for all reactions is to avoid unnecessary restriction from the
      appropriate use of latex (gloves) which provides the best barrier protection,
      while protecting individual workers from exposure that results in sensitization
      or causes sensitized individuals to have serious reactions. 4. Choose non-latex
      gloves when barrier protection from bloodborne pathogens is not an issue. When
      selecting a latex glove, choose a glove that is low in proteins and powder free
      to control airborne latex exposure.

PMID- 9526280
TI  - The influence of race and gender on health promoting behavior determinants of
      southern "at-risk" adolescents.
AB  - This article discusses the influence of race and gender on health promoting
      behavior determinants of "at-risk" adolescents living in the Black Belt region of
      Alabama. Self perception is an essential component in the likelihood to engage in
      a health promoting behavior lifestyle. There are differences in perceptual
      determinants according to race and gender. Identification in areas of difference
      is crucial to the development of intervention programs that meet students where
      they are while empowering them to make informed lifestyle behavior choices.
      Adolescents perceive themselves to have high levels of self-esteem. The challenge
      is to identify ways to enhance their self-efficacy and levels of hope.

PMID- 9526282
TI  - African American attitudes toward participation in health care.
AB  - African Americans tend to enter the health care system at the chronic stage of
      illness. Delayed knowledge results in increased morbidity (Lee & Estes, 1994). An
      understanding of factors surrounding decreased participation in formal health
      care is important for dispensers of healing as well as for African Americans who
      are themselves affected. One purpose of this study is to describe elements of an
      Africentric model and its potential for affecting nursing education and nursing
      practice. The objective for this research is to show how the Africentric model
      promotes change based on education.

PMID- 9526281
TI  - The teaching portfolio in nurse faculty evaluation.
AB  - Teaching portfolios are emerging as one of the most useful tools in faculty
      evaluation processes today. More of a summative evaluation process than a
      formative process, the teaching portfolio allows nurse faculty to document
      authentic examples of teaching effectiveness in both classroom and clinical
      settings. The use of the teaching portfolio as a mechanism to facilitate nurse
      faculty evaluation in the area of teaching is described. Practical suggestions
      concerning portfolio development and evaluation are offered.

PMID- 9526283
TI  - Diversity: a continuing challenge.

PMID- 9526284
TI  - Men still overlooked in nursing profession.

PMID- 9526285
TI  - USC offers solution to diploma-to-BSN.

PMID- 9526286
TI  - North Dakota has standardized education requirement.

PMID- 9526287
TI  - BSN-seeker objects to repeating nursing courses.

PMID- 9526288
TI  - Diversity, divisiveness and divinity.

PMID- 9526289
TI  - Divorcing the UAP: heresy or solution? Unlicensed assistive personnel.

PMID- 9526290
TI  - Massachusetts nurses, doctors spark health care revolution.

PMID- 9526291
TI  - NLRB judge rules for Massachusetts nurses in whistle-blowing case--hospital
      appeals; civil case pending.

PMID- 9526292
TI  - Grants help nurses strengthen public health.

PMID- 9526293
TI  - Oregon nurses reach out to working families through neighborhood immunization
      clinics.

PMID- 9526294
TI  - Mental disorders and culture-bound syndromes.

PMID- 9526295
TI  - Nurses need to strengthen cultural competence for next century to ensure quality
      patient care.

PMID- 9526296
TI  - Getting consent.

PMID- 9526297
TI  - Cleft palates and breastfeeding.

PMID- 9526298
TI  - Partnering for future success.

PMID- 9526299
TI  - Legislative outlook: reflections and upcoming highlights.

PMID- 9526300
TI  - Shortening the short stay.

PMID- 9526301
TI  - Home alone--meeting the needs of mothers after cesarean birth.

PMID- 9526303
TI  - Girlz 'n the 'hood--could your female patient be a gangster?

PMID- 9526302
TI  - Considering soy--its estrogenic effects may protect women.

PMID- 9526304
TI  - Building values and purpose--envisioning a successful future.

PMID- 9526305
TI  - Why mother-baby care?

PMID- 9526306
TI  - Caring for patients after pregnancy loss.

PMID- 9526307
TI  - Neonatal resuscitation--making the case for family presence.

PMID- 9526308
TI  - Endovascular repair of abdominal aortic aneurysm: an alternative to conventional
      surgery.
AB  - The majority of aortic aneurysms occur in the abdominal segment. Aneurysms above
      5 cm are at higher risk for rupture, and have traditionally been treated with
      surgical intervention. Conventional surgical treatment involves major abdominal
      surgery with associated complications. The endovascular prosthesis is a newly
      developed vascular graft which is inserted into the abdominal aortic aneurysm sac
      via a femoral arteriotomy. The procedure is less invasive for the patient, which
      is a significant benefit considering many patients with an abdominal aortic
      aneurysm are medically compromised. Thorough preoperative planning by the
      surgical and radiological teams is critical to ensure a successful patient
      outcome.

PMID- 9526309
TI  - Case costing means, measuring and managing now! The journey traveled by a
      community hospital.
AB  - Funding for health care in Ontario is moving from global funding to equity
      funding. In the future, hospitals will be reimbursed for how efficiently they
      care for their various patient populations. The Ontario Case Costing Project
      (OCCP) was a joint venture by the Ontario Hospital Association and the Ministry
      of Health. Incentive for participation in this project was based on the need to
      assess efficiencies in caring for patient populations in surgical suites and to
      obtain Canadian data. Case Costing has the potential to forecast budgets,
      identify variances and highlight areas for cost savings. Case Costing can also
      determine cost per surgeon, cost per service, cost per procedure. The nurses at
      Markham Stouffville Hospital are empowered to enhance the focus of their practice
      to include managing human resources, processes and materials. This enhanced focus
      in the Operating Room maximizes efficiency and effectiveness of processes, and
      allows the organization to provide better service. This article documents the
      journey and growth of perioperative nurses toward the destination of case
      costing. Key to this journey is not only the destination, but the growth and
      change that occurred and enabled perioperative nurses to effectively champion
      initiatives such as case costing. Opportunities and Threats, a One Page Plan and
      our recommended learnings will be shared.

PMID- 9526310
TI  - Prevention of neoplastic seeding during surgery: an investigation into OR.
      Protocols and practice in Canada.
AB  - A review in the Medical Post (Wysong, 1996) discussed the merit of glove and
      instrument changes during cancer surgery with a view to reducing the incidence of
      neoplastic seeding. This review stimulated the author to investigate current
      practices in this regard adopted by surgical staff across Canada. The author
      believes that a valid comparison exists between practices utilized in infection
      control and those which can be used to limit the problem of neoplastic seeding at
      the time of surgery. Results indicated a considerable interest in adopting a
      protocol utilizing glove and instrument changes at critical points during
      surgery, such as reconstruction and closure.

PMID- 9526311
TI  - Reuse of disposables: is it worth the risk?
AB  - The main reason institutions reuse single use medical devices is to save money.
      Most hospitals are reusing disposables in varying degrees, but few have
      thoroughly investigated the issues surrounding reuse. Are there true savings to
      be realized? What are the risks to patients and coworkers? What are the legal and
      liability hazards to our employers and to ourselves? Professional nurses have a
      responsibility as patient advocates and employees to question the validity of the
      reuse of medical devices which are manufactured to be used only once. By reusing
      disposables are we really cutting costs, or are we cutting corners?

PMID- 9526312
TI  - Cardiac spouses' help-seeking experiences.
AB  - The purpose of this study was to investigate the phenomenon of help seeking by
      spouses of cardiac rehabilitation patients by eliciting their verbal description
      of the experience. A phenomenological approach was used to collect data that
      consisted of individual interviews and focus group interviews. The exhaustive
      description of the phenomenon of help seeking described how the spouses' views of
      the illness affected initiation of help seeking. Spouses' stories revealed three
      time periods when spouses needed help: diagnosis, a time of uncertainty and loss
      of control; hospitalization, a time of information seeking and vigilance; and
      homecoming, a time of active help seeking because control is regained. To manage
      the uncertainty, spouses sought meaningful information to contend with
      difficulties. Spouses told of the individuals who assisted most, of barriers to
      seeking help, and availability of resources for support. This study increases
      health care providers' understanding of spouses' experiences, which may
      facilitate design of interviews that maximize supports for spouses. Assisting
      spouses will subsequently improve patients' recovery and facilitate lifestyle
      changes.

PMID- 9526313
TI  - Moderators of the relationship between trait anxiety and information received by
      patients post-myocardial infarction.
AB  - The purpose of this study was to examine the relationship between trait anxiety
      and patients' evaluation of information they received during hospitalization post
      myocardial infarction (MI), and to test the extent to which state anxiety and
      gender moderate this relationship. At the time of discharge from the hospital, 68
      adult men and women who had had an MI responded to a demographic data sheet and
      to instruments measuring state anxiety, trait anxiety, and the quality of
      information they received during hospitalization. Data analysis indicated that
      the higher their trait anxiety, the less positively patients rated the quality of
      information they received during hospitalization post-MI. A series of regression
      analysis procedures designed to test for moderation indicated that neither state
      anxiety nor gender had a moderator effect on the relationship between trait
      anxiety and the quality of information received. The findings are interpreted
      within the theoretical perspectives that guided the study. Clinical implications
      of the findings are discussed.

PMID- 9526314
TI  - Psychosocial adjustment of males on three types of dialysis.
AB  - End-stage renal disease (ESRD) is a chronic illness that challenges the coping
      ability of patients and their families, demanding behavioral and emotional
      lifestyle changes. The purposes of this comparative descriptive study were to
      explore the anxiety, depression, and psychosocial adjustment of male patients on
      three types of dialysis--home hemodialysis (home HD), in-center hemodialysis (in
      center HD), and peritoneal dialysis (PD)--and to identify perception of
      hemodialysis stressors for those on home HD and in-center HD. Five subjects in
      each of the three groups (N = 15), matched for age, gender, education, and
      dialysis type, participated in the study. Although the convenience sample size is
      too small to generalize, subjects on home HD demonstrated higher psychosocial
      adjustment. The study supports further research with larger, randomized samples.
      Information about psychosocial adjustment of patients on each type of dialysis
      provides information for nurses as they guide patients in choosing dialysis type.

PMID- 9526315
TI  - Elder care among Mexican American families.
AB  - This exploratory study describes caregiving experiences of elderly family members
      as perceived by eight Mexican American women caregivers and characterizes the
      ideas that some Mexican Americans have about elder care. A qualitative approach,
      using open-ended questions, revealed a cultural picture that reflected a very
      rich cultural heritage. This picture includes the importance of the family's
      responsibility to care for its elder members and describes family commitments
      that reach beyond obligation. It also portrays a complex system of cultural
      beliefs and values that are based on Mexican American tradition. The themes of
      reciprocity and point of reckoning emerged as two descriptive characteristics of
      the Mexican American family in the southwestern United States that form the basis
      for the restructuring of a woman's responsibilities during middle age. This study
      indicated that the bicultural lens through which the caregiver views the world
      may differ markedly from that of the elderly family member.

PMID- 9526317
TI  - Implementing lessons we learned as children.

PMID- 9526318
TI  - Cutaneous injuries in women athletes.
AB  - Positioned at the interface between the athlete and her sports environment, the
      skin bares the brunt of multiple forces, many of which result in cutaneous
      trauma. Although this subject has been reviewed in considerable detail, we wish
      to focus on those injuries which are unique to women competitors and fitness
      advocates either exclusively, or more commonly, with equal or greater frequency
      than their male counterparts. We hope that these topics will be of value to
      dermatology nurses in answering questions on the subject both in and out of the
      clinical setting.

PMID- 9526316
TI  - Adolescents' perceptions of pain during labor.
AB  - This descriptive study systematically described the quality and intensity of
      adolescents' pain during the progression of labor. The Gaston-Johansson Pain-o
      Meter was administered to 33 adolescents during the three labor phases (2-4 cm, 5
      7 cm, and 8-10 cm) following a contraction. The most frequently selected sensory
      words were cramping in Phase I and pressing in Phases II and III. Miserable and
      killing were the most commonly chosen affective words during the three labor
      phases. Using the Gaston-Johansson Pain-O-Meter and the Gaston-Johansson Pain-O
      Meter Visual Analogue Scale, the total pain intensity scores were highest during
      phase III of labor and delivery. At-test of independent samples found that
      quality and intensity pain scores for primiparous and multiparous adolescent
      participants were not significantly different during the progression of labor.
      The findings of the study illustrate the value of using objective measures, such
      as the Gaston-Johansson Pain-O-Meter and the Gaston-Johansson Pain-O-Meter Visual
      Analogue Scale, to assess pain during labor. The study also demonstrated that
      nurses can use these tools with minimal training.

PMID- 9526319
TI  - Cutaneous manifestations of malignant disease.
AB  - The focus of this article is to discuss cutaneous manifestations of systemic
      malignant disease. Primary skin cancers will not be presented. While metastasis
      to the skin is a rare event, it is important for dermatology nurses to recognize
      that it can occur.

PMID- 9526320
TI  - Atopic dermatitis in childhood.
AB  - Atopic dermatitis is one of the major challenging skin disorders in infants and
      children. Many flare factors come into play. Treatment is complicated. A
      simplified approach and overview to the problem is presented here. A parent
      education handout used in our clinic and reprinted here may be reproduced for
      patient education purposes.

PMID- 9526321
TI  - What's your assessment?Eruptive xanthomas.

PMID- 9526322
TI  - Flannel board stories: an innovative method of teaching sun protection.
AB  - Using sunscreen daily should be as natural for children as brushing their teeth.
      Flannel board stories can make this happen by serving as an innovative technique
      for educating children about sun protection.

PMID- 9526323
TI  - Assessing the nutritional needs of the geriatric patient with diabetes.
AB  - The 1994 Nutrition Guidelines reinforce that all nutritional plans for people
      with diabetes should be individualized, which is particularly important and
      necessary for elderly patients. The geriatric population poses many unique
      challenges to the healthcare professional due to physiological changes and many
      other risk factors that affect nutritional status either directly or indirectly.
      A thorough nutritional assessment that includes an evaluation of the potential
      nutritional risk factors described in this article can help in developing an
      effective and realistic nutritional plan for achieving and maintaining good blood
      glucose control and good nutritional status in geriatric patients with diabetes.

PMID- 9526324
TI  - Developing a patient education program: overcoming physician resistance.
AB  - Scientific expertise in the management of diabetes was an important factor in
      overcoming physician resistance to the education program. Nurses have expertise,
      and their expertise must be acknowledged for them to be viewed as leaders. Not
      only are nurses responsible for sharing their expertise with other nurses, it is
      equally important for them to share their expertise with the physicians, who may
      appreciate receiving any information that can help them improve their patients'
      outcomes. The components that are essential for success in pioneering a new
      program are good listening skills, a willingness to cooperate, self-confidence,
      scientific knowledge, vigilance, determination, and a clear vision. Patient
      outcomes will improve when nurses use their scientific knowledge base and
      leadership skills through patient-centered nursing practice, planned change
      strategies, and advanced practice nursing.

PMID- 9526325
TI  - An invitational counseling approach to diabetes management.
AB  - It is important for healthcare professionals to be nonjudgmental and provide a
      supportive, caring environment both personally and professionally when working
      with patients with diabetes. The challenge is to invite patients to be successful
      in managing their diabetes by building helping relationships based on the
      invitational counseling model. A positive, empathetic, and intentionally inviting
      healthcare team may be one of the keys to successful management of diabetes.

PMID- 9526326
TI  - Metabolic control, quality of life, and negative life events: a longitudinal
      study of well-controlled and poorly regulated patients with type 1 diabetes after
      changeover to insulin pen treatment.
AB  - In a previous study of a group of 74 patients with Type I diabetes, quality of
      life was found to be consistently enhanced a year after transition to multiple
      injection therapy with the insulin pen, whereas metabolic control (HbA1C) only
      improved moderately. The aim of the present investigation was to examine quality
      of life, recent life events, and metabolic control longitudinally in this
      original study group over a 5-year period beginning 1 year after transition to
      the insulin pen. Multiple analysis of variance with a repeated-measures design
      was used to analyze the data longitudinally and compare metabolic control in
      subgroups of well-controlled and poorly regulated patients during the study
      period. For the group as a whole, quality of life was found to change only
      moderately, whereas metabolic control deteriorated significantly across time
      following transition to the insulin pen. The two subgroups exhibited distinct
      differences, however, in quality of life, recent life events, and metabolic
      control patterns. These findings are discussed in terms of the clinical
      suitability of a multiple injection regimen.

PMID- 9526327
TI  - Attitudes and issues in treating Latino patients with type 2 diabetes: views of
      healthcare providers.
AB  - The purpose of this study was to explore the concerns of Latino patients with
      Type 2 diabetes. Focus groups were conducted with healthcare practitioners to
      chart their perceptions of the issues faced by their Latino patients. One group
      consisted of professionals working among Mexican American clients in an inner
      city clinic; another group was held at an inner-city hospital serving mostly
      Puerto Rican Americans; and a third group involved providers practicing with more
      affluent, suburban Mexican Americans. Practitioners agreed that communication
      with patients was hindered by low reading levels, lack of proficiency in English,
      and an excessive respect for physicians. Emotional barriers to adequate treatment
      were often more important than financial concerns, even among low-income
      patients. Fear of insulin therapy was expressed in Hispanic communities, and folk
      remedies were commonly used. Because family needs were considered most important,
      adhering to a treatment regimen might be viewed as self-indulgent. Yet families
      provided valuable reinforcement and emotional support. Important questions facing
      Latinos with diabetes were effectively identified using focus groups of
      healthcare providers.

PMID- 9526328
TI  - Struggling with behavior changes: a special case for clients with diabetes.
AB  - Health professionals expect clients with diabetes to change multiple behaviors as
      a way to decrease the risk of complications of the disease. The purpose of this
      study was to gain an in-depth understanding of the client's response to lifestyle
      change expectations. Using the transtheoretical model of change as framework for
      this study, clients were asked to address the level of difficulty they
      encountered when making lifestyle changes relating to their diabetes. Ten clients
      who participated in a taped telephone survey and a videotaped focus group
      reported that most change was difficult but not impossible. Most clients admitted
      that maintaining changes was a continuing battle. Both the transcripts and focus
      group revealed a wide variation in the clients' understanding of self-management.
      It was evident that successful management involves a fairly high level of
      cognition as well as willingness to change. Successful management involves
      thinking through and comprehending how diet, exercise, and medication relate to
      blood glucose levels. This preliminary study will be used as the basis for a more
      inclusive study that will focus on developing interventions that relate directly
      to helping clients change behavior.

PMID- 9526329
TI  - A primer on the use of insulin pumps in adolescents.
AB  - Optimal metabolic control to minimize long-term complications is a major
      treatment goal for adolescents with diabetes mellitus. Reaching this goal is
      extremely challenging in this population due to unique physiological changes and
      psychosocial variables that affect metabolic control. Continuous subcutaneous
      insulin infusion (CSII) may be an excellent treatment alternative for selected
      adolescents to help overcome some of these challenges. CSII allows for minute
      insulin changes at variable times throughout the day, providing greater lifestyle
      flexibility. The purpose of this paper is to review the use of insulin pump
      therapy in adolescents. Specific strategies regarding screening, initiation, and
      maintenance of this therapy are described, and case examples are used for
      illustration. Implications for nursing practice and diabetes education are
      discussed.

PMID- 9526330
TI  - Impact on clinical status and quality of life of switching from regular insulin
      to insulin lispro among patients using insulin pumps.

PMID- 9526331
TI  - Effects of reminiscence on life satisfaction of elderly female nursing home
      residents.
AB  - The author investigated the efficacy of a reminiscence group in increasing life
      satisfaction in elderly female nursing home residents. E. Erikson's (1982)
      developmental theory and R.N. Butler's (1981) theory of reminiscing provided the
      theoretical framework for the study. It was hypothesized that reminiscing would
      increase life satisfaction when measured by the Life Satisfaction Index A
      (Neugarten et al., 1961). The design was experimental, using pretest and posttest
      data collection. Thirty-six female nursing home residents over 65 years of age
      were randomly assigned to a reminiscing group or a control group. A statistically
      significant difference (p = .03) was found between the reminiscing group and the
      control group on the dependent variable, life satisfaction, when data were
      analyzed using an analysis of covariance. Implications for research and practice
      are discussed.

PMID- 9526332
TI  - Female genital mutilation and public health: lessons from the British experience.
AB  - The author addresses the public health policy challenge posed by the increasing
      numbers of immigrant girls and women in the United States affected by female
      genital mutilation (FGM), a traditional ritual health practice in which part or
      all of the external genital structures are removed from females, usually during
      childhood. The practice is common today in 26 African nations and affects 100 to
      126 million women and girls worldwide. The significant lifelong negative health
      impact of FGM has been documented. Recent developments in British domestic health
      and social policy are reviewed to provide insights. The definition of FGM,
      prevalence, health impact, and history of the practice are presented.
      Implications for the development of health and social services policies and
      programs in the United States are drawn.

PMID- 9526333
TI  - HIV infected women and women's services.
AB  - HIV/AIDS is increasing faster in women than any other segment in the population.
      The typical woman who is HIV infected is young, poor, a minority, and in the
      childbearing stage of life. Only 1 study was found that explored medical services
      in relation to usage and cost by men and women infected with HIV (F.J. Hellinger,
      1993). The purpose of this study was to examine the types of services and the
      groupings of those services within facilities that were offered for women who
      were HIV positive. Seventeen of the 28 facilities (61%) that provide care to this
      population responded to a telephone survey. The research suggests that care for
      women who are HIV positive is fragmented, and there are access barriers to care
      and support. Many services that are especially important to HIV-infected women
      were not found or were not made available by many facilities.

PMID- 9526334
TI  - AIDS awareness among women: the benefit of culturally sensitive educational
      programs.
AB  - AIDS affects everyone, regardless of race, age, or religion; hence, information
      must be accessible to everyone. This descriptive study identified the need to
      generate culturally sensitive educational programs and evaluated their effect.
      Culturally sensitive AIDS educational training was offered to culturally diverse
      women. Training was conducted by women of the same ethnicity as the women in the
      group. The facilitators were specially trained on the role of a facilitator and
      the participatory method of learning. To assess any change in attitude,
      knowledge, and beliefs regarding AIDS, the questionnaire was administered before
      and after the training programs. Educational training had a positive effect (p <
      .05) on participants' attitude and knowledge regarding AIDS; they felt
      comfortable discussing their concerns in their own language, and with their
      friends from the same community, and they viewed the resources used as culturally
      sensitive.

PMID- 9526335
TI  - Prevalence and factors associated with physical and sexual assault of female
      university students in Ontario.
AB  - The authors examined the prevalence of physical and sexual assault of female
      university students and associated factors. In a survey of a random sample of
      3,642 female students from 6 universities across Ontario, 24% of female students
      reported being physically assaulted and 15% reported being sexually assaulted
      during the previous year. When the assault measures were combined, 32% of
      university women reported being either physically or sexually assaulted during
      the previous year. Of those experiencing assault, 40% had been the victim of 2 or
      more types of assaults. Logistic regression analysis revealed that assault was
      associated with year of study, marital status, alcohol consumption, illicit drug
      use, prescription drug use, unhealthy eating and stress behaviors, less time
      spent on academics, and more time involved in social activities. University
      programs and activities directed toward the reduction of assault should
      incorporate the factors identified in this study to increase awareness of the
      situational factors surrounding likelihood of assault.

PMID- 9526336
TI  - Breast care among Latino immigrant women in the U.S.
AB  - Although the U.S. is recognized as a developed country, knowledge of how to
      perform a breast self-examination (BSE) and the availability and accessibility
      screening mammography are not evenly distributed across ethnic, racial, and
      socioeconomic groups. Some U.S. organizations have decreased their emphases on
      BSE and are strongly promoting technological advances such as mammography.
      Disparities in obtaining breast health care are found worldwide. In this article
      we present the findings of a study that was conducted in a large urban area in
      the Midwest of the United States, to identify factors associated with breast care
      in Latino immigrant women (n = 111). Limited knowledge about breast care,
      unemployment, and short period of residence in the U.S. were all found to be
      related to inadequate breast care in this group of women. These findings have
      global implications for health care practitioners in directing attention toward
      discovering factors that promote and inhibit early breast cancer detection.

PMID- 9526337
TI  - Self-care also means taking care of yourself.

PMID- 9526338
TI  - How students nurses see home healthcare nurses today.
AB  - Students in an associate degree nursing program participated in observational
      home healthcare experiences. By observing the interactions between the
      client/family and the home healthcare nurse, these students noted crucial
      differences between the delivery of acute and home care nursing. Their
      observations can be helpful to practicing home care nurses who serve as their
      role models and to orientation coordinators and faculty members who teach home
      care nursing to novices.

PMID- 9526339
TI  - Sooo ... you decided to go to graduate school.

PMID- 9526340
TI  - Home health graduate nursing programs in the United States.

PMID- 9526341
TI  - Call of the wild.

PMID- 9526342
TI  - Problematic standard: advance directives.

PMID- 9526343
TI  - Elder abuse: a challenge for home care nurses.
AB  - Healthcare practitioners are aware that elder abuse exists in our society, and in
      light of present economic conditions, its prevalence may be increasing. This
      problem often goes undetected because abuse frequently is not acknowledged by the
      abused or the abuser. Home care nurses are in a prime position to recognize elder
      abuse and to intervene accordingly. This article addresses the characteristics of
      abused older adults, their abusers, strategies to detect elder abuse, and
      interventions that home care nurses can use to manage or to prevent the problem.

PMID- 9526344
TI  - Patient silence is not necessarily client satisfaction: communication problems in
      home care nursing.
AB  - Although we may believe we are inviting client feedback about care, it is clear
      from a recent study surveying home care providers and older adult care recipients
      that failures in communication continue to plague us. Inadequate communication
      can lead to misunderstandings, client and provider dissatisfaction, and even
      termination of the home care provider-client relationship. By strengthening
      communication skills, staff can see changes in client satisfaction, have greater
      success in resolving potential problems, and may ultimately experience more job
      performance satisfaction.

PMID- 9526345
TI  - The clinical use of aromatherapy in the reduction of stress.

PMID- 9526346
TI  - Benefits of managed care.

PMID- 9526347
TI  - Gerontological nursing: whither now?

PMID- 9526348
TI  - Preparation for family care-giving: stroke as a paradigm case.
AB  - This article considers the nurse's role in assisting family (informal) carers who
      adopt their role suddenly, following an acute health crisis. Carers of stroke
      survivors are used as a 'paradigm' case to highlight the challenges faced by
      family members at the time of hospital discharge. The needs of family members who
      suddenly adopt a caring role are poorly understood, but greater awareness is
      needed as the Carers (Recognition and Services) Act (1995) provides statutory
      recognition of the rights of such individuals to an assessment of their needs,
      emphasizing the importance of carers making an informed choice based on a
      willingness and ability to adopt a care-giving role. Evidence suggests that new
      family carers are currently poorly prepared to take on their role, lacking the
      information and skills needed to provide good care. Nurses have a major role to
      play in preparing carers, but currently lack a systematic approach to assessment
      and intervention. Further empirical work is required to establish more clearly
      the needs of new carers and to develop and evaluate appropriate intervention
      strategies to address their needs.

PMID- 9526349
TI  - The challenges of improving discharge planning in Sweden and the UK: different
      but the same.
AB  - Discharge of older people from hospital has been an area of concern for over 20
      years. The present emphasis on rapid throughput of patients in acute care
      settings is likely to exacerbate existing problems. Improving current practice
      will mean addressing a number of complex issues to do with communication between
      agencies and professions. Despite different welfare systems, many of the
      challenges of discharge planning are shared in different countries. This paper
      describes attempts to involve patients and carers in discharge planning in Sweden
      and the UK and identifies a number of areas which require attention if the ideals
      of patient and carer empowerment are to be achieved.

PMID- 9526350
TI  - Admission to care: facilitating role transition amongst family carers.
AB  - Admission to care after a period of family care-giving has been the focus of much
      recent research. Rather than being seen as an end in itself, admission is part of
      a process. This article concentrates on 'reaching the end' of family care-giving
      and the 'new beginning' of entering residential care. A cross-national study
      conducted in the USA and the UK is discussed, and similarities and differences in
      the two cultures are highlighted. Decisions to enter a nursing home were often
      taken hurriedly and with lack of information in both countries. Issues of quality
      of care and emotional responses by former carers were also important in both
      settings.

PMID- 9526351
TI  - An attempt to give nursing home residents a voice in the quality improvement
      process: the challenge of frailty.
AB  - Advanced frailty and confusion of many nursing home residents present a
      particular conundrum to researchers committed to resident participation. While
      the research is set in Australia, the challenge of frailty is common to
      researchers working with compromised older persons. This study was conducted in
      an Australian 32 bed nursing home. As researchers we took on the roles of
      facilitators and negotiators within a quality improvement process using the
      approach of fourth generation evaluation. The overall aim of the project was to
      provide all stakeholders, including residents and their significant others, with
      a voice in the negotiations and decisions that impact on their lives. The focus
      of this paper is our attempt to gain the perspective of residents and significant
      others.

PMID- 9526352
TI  - Moving from hospital into a care home--the nurse's role in supporting older
      people.
AB  - Discharge planning has received much attention in the nursing literature over the
      past few years, and there has been particular concern over the discharge of older
      people back into their domestic environment. The practical and logistical
      problems of managing such a discharge are considerable, but in this paper we
      argue that discharging older people from hospital to care homes is equally
      problematic, though in different ways. This is a neglected area of research,
      perhaps because discharge into a care home seems to present fewer organizational
      problems. There is, however, an extensive body of literature from a range of
      different disciplines which suggests that the loss of home and entry into a
      strange environment can be very stressful. This paper outlines this literature
      and explores the implications for nursing practice.

PMID- 9526353
TI  - Spousal caregiving in the institutional setting: visiting.
AB  - The purpose of this study was to investigate the visiting experience of wives
      whose husbands had been admitted to a long-term care institution. The study
      employed a longitudinal and prospective design and combined qualitative and
      quantitative approaches. The data were drawn from a larger study designed to
      explore the transition to quasi-widowhood. This article reports on one aspect of
      spousal caregiving following the admission of a husband to a long-term care
      setting, i.e. visiting. In this study, wives visited frequently. Their reasons
      for visiting included love and devotion, duty and obligation, the monitoring of
      husbands' well-being and the provision of assistance to both husbands and staff.
      They engaged in task performance and social interaction during visiting. Their
      feelings of satisfaction and enjoyment with visiting were associated with their
      husbands' well-being and feeling useful. Over the 9-month period of the study,
      two patterns of visiting and involvement emerged that were associated with
      different outcomes related to depression, morale and satisfaction with
      institutional dimensions of care.

PMID- 9526354
TI  - Evaluation of a new night nursing service for elderly people suffering from
      dementia.
AB  - A new night hospital nursing service was developed for older people with
      dementia. A case study approach to evaluation was adopted using a structure
      process-outcome quality assurance cycle. The effects and attendance of patients
      are reported and discussed. Discussion relating to care provision for the future
      is presented. The effects on carers of patients' attendance are briefly
      discussed.

PMID- 9526355
TI  - Including patient preferences in nurses' assessment of older patients.
AB  - The refinement of a patient assessment tool for older patients, Lorensen's Self
      Care Capability Scale, is described where a systematic elicitation of patient
      preferences is included in the assessment. This study tests a decision analytic
      approach as a strategy for formalizing subjective judgement, which makes it
      possible to include patients' own values and preferences in planning patient
      care. Applying this technique to patient assessment contributes to explicitly
      tailoring nursing care decisions to desired outcomes as preferred by individual
      patients. A shared approach to decision making between nurse and patient ensures
      a mutual understanding about goals, priorities and patient values through
      discussion and negotiation. This pilot study supported the merit of including
      patient preferences systematically in the assessment of older patients. The
      method provides an important decision aid for nurses in planning nursing care in
      accordance with patients' own values and preferences for care.

PMID- 9526356
TI  - Family and staff involvement in treating dementia patients in nursing homes.

PMID- 9526357
TI  - Kasabach-Merritt syndrome: a case review.
AB  - Hemangiomas are common newborn vascular tumors occurring in up to 2.5 percent of
      newborns. Most are benign and 70 to 80 percent regress by age seven. Some
      hemangiomas are life threatening--1 in 300 is associated with coagulopathy.
      Kasabach-Merritt syndrome (KMS), associated with hemangioma, disseminated
      intravascular coagulopathy, microangiopathic anemia, and thrombocytopenia, can
      have profound sequelae. Morbidity and mortality are influenced by the anatomic
      location and size of the hemangioma. Untreated KMS has a 10-37 percent mortality
      rate. Bleeding secondary to the consumptive coagulopathy is the primary cause of
      death in these patients. As of 1997, there have been approximately 205 cases of
      KMS reported in the literature. This case study discusses the pathophysiology,
      clinical manifestations, diagnostics, treatment modalities, differential
      diagnosis, and psychosocial considerations of KMS.

PMID- 9526358
TI  - Heelsticks in neonates for capillary blood sampling.
AB  - Capillary blood sampling via a heelstick is a common procedure performed on
      hospitalized neonates. If not performed properly, a heelstick can lead to
      complications. The clinical and financial impact of complications and redrawing
      of blood can be significant. Lancets/lancing devices are reviewed and proper
      procedure is discussed.

PMID- 9526359
TI  - Severe congenital nemaline myopathy: a personal perspective.
AB  - Severe congenital nemaline myopathy is an uncommon but often fatal muscular
      disease. Dealing with this disorder can be devastating to both family and NICU
      staff. It can be difficult to diagnose because symptoms often mimic symptoms of a
      postasphyxial insult. Continued dependence on mechanical ventilation in the
      absence of severe brain damage or other cardiac or respiratory disease may be the
      only indication of this disorder. This article records the author's personal
      experience of caring for an infant with the severe form of nemaline myopathy.

PMID- 9526360
TI  - Parent perceptions of an NICU follow-up clinic.
AB  - PURPOSE: To learn how parents perceived their experiences during a visit to an
      academic center's NICU follow-up clinic and what they would change about the
      clinic if given the opportunity. DESIGN: A qualitative study utilizing artifact
      collection, participant observation, and semistructured interviews. SAMPLE: Seven
      families that went to the clinic. MAIN OUTCOME VARIABLE: What parents did and did
      not like about the clinic and what they would change about the clinic. RESULTS:
      Parent concerns included lack of information about the clinic prior to the first
      appointment, length of wait prior to seeing the physician, preference for more
      appropriate toys for use during the wait, desire for additional explanations
      during the exam process, uncertainty about the effects of prematurity on their
      child's development, and need for more developmental and parenting information.

PMID- 9526361
TI  - Rickets screening in the preterm infant.
AB  - Although rickets in the preterm infant has decreased with improvements in care
      and nutrition, there continue to be infants at high risk for this disease. Early
      diagnosis and treatment can prevent fractures and other complications, such as
      decreased linear growth. Nurses must know which infants are at risk, must be
      aware of the appropriate screening tests, and must know how to customize care for
      at-risk neonates.

PMID- 9526362
TI  - Ten commandments of peer review.

PMID- 9526363
TI  - Neonatal peritoneal dialysis: a guide.

PMID- 9526364
TI  - Impact of HCFA's revised billing instructions for kinetic modeling and
      recirculation tests.

PMID- 9526365
TI  - The rationale for improving outcomes on dialysis by actions prior to and at
      initiation.

PMID- 9526366
TI  - LORAC recognizes five dialysis facilities for exemplary practices in
      rehabilitation.

PMID- 9526367
TI  - Latex allergies in the health care setting. A review of the problem and some
      solutions to address the issue.

PMID- 9526368
TI  - Implementing the DOQI guidelines--the nephrology social worker's role.

PMID- 9526369
TI  - A retrospective analysis of employee turnover in the health care setting.
AB  - Significant factors implicated in staff turnover include: variables in
      organizational structure; employee characteristics; needs and values, and the
      nature of tasks performed. This article will present the causative factors
      related to turnover and the conceptual models of the motivational theorists
      Maslow, Herzberg, Adams, and Mobley. No quantitative or qualitative research
      could be found on the potential causes of turnover in freestanding dialysis
      clinics. The staff turnover of a for-profit dialysis company for a 12 month
      period will be reported by job title, tenure, and level of job satisfaction.

PMID- 9526370
TI  - Charting tips--avoiding generalizations.

PMID- 9526371
TI  - Treating a fungal infection.

PMID- 9526372
TI  - Megestrol and impotence--teaching patients about this dose-related adverse
      effect.

PMID- 9526373
TI  - Understanding sexually transmitted diseases, Part I.

PMID- 9526374
TI  - Easing the discomfort of venipuncture.

PMID- 9526375
TI  - Failure to heed "no code blue".

PMID- 9526376
TI  - Actionstat. Wound dehiscence.

PMID- 9526377
TI  - Administering steroids successfully.

PMID- 9526378
TI  - VRE & MRSA--putting bad bugs out of business.

PMID- 9526380
TI  - Caring for patients with pericarditis.

PMID- 9526379
TI  - Then an angel came.

PMID- 9526381
TI  - What we learned from the Oklahoma City bombing.

PMID- 9526382
TI  - Removing a PICC?--proceed with caution (peripherally inserted central catheter).

PMID- 9526383
TI  - Troubleshooting chest tubes.

PMID- 9526384
TI  - Creating a positive first impression.

PMID- 9526385
TI  - Tackling a new project.

PMID- 9526386
TI  - Are you kidding?

PMID- 9526387
TI  - Giving medication through an enteral feeding tube.

PMID- 9526389
TI  - Case management and job satisfaction.

PMID- 9526388
TI  - Family values.

PMID- 9526390
TI  - Designing measurements to assess case management outcomes.
AB  - Evaluating outcomes begins with determining the goals of case management. As the
      emphasis on the delivery of cost-effective patient care increases, comparing
      outcomes across settings is desirable and essential. A key component to comparing
      how an organization rates with similar institutions is to identify commonly used
      measures. Conducting a literature search, benchmarking, participating in
      initiatives of accrediting bodies, and establishing ways to collect and manage
      reliable and valid data are vital in laying the groundwork for an organization's
      ability to join evaluation projects across settings.

PMID- 9526391
TI  - Nursing, technology, and patient care: a home-based model.

PMID- 9526392
TI  - Job design for nurse case managers. Intended and unintended effects on
      satisfaction and well-being.
AB  - As managed care expands, nursing case management is becoming increasingly
      widespread. Yet little is known about the characteristics of the case manager job
      and its effects on nurses' workplace well-being. This study investigated
      hypothesized differences between the characteristics of nurse case manager and
      staff nurse jobs, including both intended positive and unintended negative
      effects associated with changes incorporated in the nurse case manager job. Nurse
      case managers reported significantly higher levels of autonomy, job identity,
      feedback from agents, and collaboration with physicians than staff nurses;
      however, they also reported higher levels of required interaction, role conflict,
      overload, and ambiguity. These findings have important implications for nurse
      case manager and the organizations that employ them, in relation to job design,
      career/candidate selection, and orientation and ongoing development.

PMID- 9526393
TI  - Improving care with a pediatric appendicitis pathway.

PMID- 9526394
TI  - Communication action for case managers. Techniques to manage conflict.
AB  - The art of communication can facilitate case management in an optimum sense. It
      can also create conflict issues if handled inappropriately. In this article, the
      authors explore the basic tenets of the communication process. On this basic
      foundation, conflict and approaches to conflict resolution are explored.
      Specifically, Kare Anderson's Triangle Talk model is used in conjunction with a
      specific case that demonstrates the potential for positive communication
      outcomes. The model offers three principles, which are discussed individually.
      Good communication skills are a prime component of therapy and case management.
      It is important to the case outcome that the communication is done well. However,
      it is unusual for health care providers to have specialized training in the
      skills of conflict negotiation. The authors offer the reader an opportunity to
      apply what is presented in this article in a self-study module at the end.

PMID- 9526396
TI  - Education or expense?

PMID- 9526395
TI  - The multidisciplinary mandate of clinical pathways enhancement.

PMID- 9526397
TI  - At risk from gender care?

PMID- 9526398
TI  - Defeating depression.

PMID- 9526399
TI  - Discounted complaints.

PMID- 9526400
TI  - Jonathan Asbridge. Interview by Tom Keighley.

PMID- 9526401
TI  - Failure to manage.

PMID- 9526402
TI  - Focus on the future.

PMID- 9526404
TI  - Costing care.

PMID- 9526403
TI  - Quality at the bottom.

PMID- 9526405
TI  - Caring together: clinical supervision.
AB  - Clinical supervision is an effective learning and development tool which nurses,
      and other healthcare professionals, can use to promote and maintain high
      standards of patient care. This Unit explains the concept behind clinical
      supervision and looks at the work carried out nationally to develop its use in
      practice. Clinical supervision has been shown to offer many benefits for the
      individual practitioner, the supervisor and the organisation and these are
      discussed in detail; as are the various methods and models which can be employed
      to implement clinical supervision. A knowledge of these models and the possible
      outcomes they can elicit for the individual is important, because it will allow
      the participants to tailor the process for their own special needs. Lastly, the
      essential element of evaluating the process is discussed. This is vital for
      supporting evidence-based practice in health care and providing positive outcomes
      for patient care.

PMID- 9526406
TI  - Infections in total joint replacements.
AB  - This article helps orthopaedic nurses identify patients most susceptible to
      infection, to identify signs and symptoms of infected joints, and to understand
      current treatment regimens. The incidence of infection in total joint
      replacements (TJR) is low, but once infection is established, the morbidity is
      high and the limb may be threatened. Infection remains one of the most
      devastating complications of TJR, and the goal is to prevent all TJR infections.

PMID- 9526407
TI  - Managing the surgical orthopaedic patient with Parkinson's disease.
AB  - Parkinson's disease is a chronic, progressive, disabling, neurologic disorder
      that can complicate the diagnosis, clinical course, and recovery from comorbid
      conditions, such as traumatic fractures. Attention to specific aspects of
      management ought to minimize morbidity and facilitate orthopaedic recovery,
      notably medication titration and airway protection, hemodynamic stability, and
      surveillance proportional to mental capacity. Classical orthopaedic management
      may have to be altered, especially if the patient has advanced neurologic
      disease. Optimal management of patients with combined surgical orthopaedic and
      neurologic disease offers the treatment team an unusual opportunity to
      collaborate and coordinate multiple facets of care.

PMID- 9526408
TI  - Clinical insights for office practice management.
AB  - This manual is intended to be an easily used reference tool for office nurses who
      are involved with orthopaedic practice management. The manual can be enhanced
      with personal annotation, creating a working desk reference. While it is beyond
      the scope of this publication to be a textbook of ambulatory nursing, concepts
      will be introduced, ideas shared, and resources listed without pretense of
      attempting to instruct nurses in the science of ambulatory nursing. Some sections
      are in question and answer format. This will guide the reader through situations
      commonly encountered and provide possible solutions applicable to individual
      settings. Because office/clinic nursing is diversified in setting and clinical
      focus, it is beyond the scope of this manual to provide answers applicable for
      all situations. Sections have been included regarding office setup, equipment
      issues, space requirements, regulations, certification, and accreditation.
      Contributing authors have provided expert information on managed care issues,
      CPT/ICD9 coding, risk management, and OSHA regulations. By outlining common areas
      of concern and pitfalls to avoid, nurses can develop a workbook specific to their
      own setting.

PMID- 9526409
TI  - Patient and family perspectives on early discharge and care of the older adult
      undergoing fractured hip rehabilitation.
AB  - PURPOSE: To examine the impact of enhanced early discharge on families
      experiencing repaired hip fracture in an older adult. DESIGN: Qualitative.
      SAMPLE: Convenience sample of 23 care recipients over the age of 60 years who had
      experienced a hip fracture and their caregivers. METHODS: Families were
      interviewed 4 to 6 weeks postdischarge from the hospital. Prior to the interview
      a questionnaire designed to measure intra-family strain was mailed to the main
      caregiver. The resulting narratives were analyzed for recurring themes. FINDINGS:
      A high number of clients and their families experienced a high degree of
      mismatched care, especially in relation to care received by nursing staff. This
      perception was not influenced greatly by location (i.e., hospital or community)
      and was exacerbated during periods of transition. CONCLUSION: Heightened
      communication involving clients and families, especially during transition from
      hospital to home, may lessen family/client perceptions of mismatched care.
      IMPLICATIONS FOR NURSING RESEARCH: Communication methods, role clarification of
      the professional nurse, and the ability to provide more holistic care during
      transition phases of health care are areas that need to be explored and
      developed.

PMID- 9526410
TI  - Issues related to cardiac monitoring on an orthopaedic unit.
AB  - Nurses on a variety of medical surgical units are being asked to care for
      patients being monitored for cardiac dysrhythmias. Basic information needed by
      nurses caring for these patients includes understanding the fundamentals of
      cardiac monitoring such as the components of the cardiac cycle and electrode
      placement. A working knowledge of cardiac dysrhythmia interpretation is
      essential. Protocols for emergent treatment of dysrhythmias must be in place, and
      a program for maintaining proficiency should be developed. Yearly refresher
      programs can be provided, including validation of dysrhythmia interpretation
      skills and problem solving of case-based scenarios. Any program supporting
      development and maintenance of a skill such as cardiac monitoring requires
      ongoing validation.

PMID- 9526411
TI  - A review of cardiac medications for the orthopaedic nurse clinician.
AB  - Cardiovascular disease remains a major health problem in today's society. It is
      estimated that more than 6 million people have a history of myocardial infarction
      and/or angina (Abraham, 1995). Hypertension is another major health problem
      affecting at least 50 million people in the United States (Johannsen, 1993). Due
      to the high prevalence of these conditions, many orthopaedic patients will be
      taking one or more cardiac medications. This article discusses the indications,
      mechanisms of action, side effects, and nursing implications for the major
      classes of cardiac medications. The purpose of this article is to enhance the
      nurse clinician's knowledge of these medications and to optimize the patient's
      nursing care.

PMID- 9526412
TI  - Child abuse: assessment and intervention.
AB  - The National Statistics on Child Abuse and Neglect are staggering and rising
      despite a national objective to decrease domestic violence, of which child abuse
      is a part. More than 3 million children are abused each year. That figure
      represents 25 out of every 1,000 children being physically, sexually, or
      emotionally abused or neglected by their caretakers. It is important to note that
      50% of abused children have an abused mother (American Medical Association,
      1992). There are immediate as well as long-term sequelae of abuse including
      emotional and developmental problems, permanent injury, death, and perpetuation
      of abuse to the next generation. Since fractures are often part of the
      constellation of injuries seen in the abused child, orthopaedic nurses may
      encounter these children in a range of settings. Recognizing the signs of abuse
      is an important step for intervention on behalf of the child.

PMID- 9526413
TI  - Reiter's syndrome.
AB  - Frustrating and baffling are words used with Reiter's syndrome as there is much
      yet to be learned about this reactive arthritis. Having an understanding of the
      pathology, disease manifestations, and progress of the condition enables the
      nurse to better assess and manage care for these patients.

PMID- 9526415
TI  - Pressure ulcers and the control of care.

PMID- 9526414
TI  - Perioperative blood management.
AB  - Perioperative blood management has evolved in recent years, and new approaches to
      blood conservation and replacement have dramatically changed the treatment of
      surgical patients. This article addresses the historical continuum of blood
      transfusions and describes current standards of practice in perioperative blood
      management in orthopaedic patients. Certain elective orthopaedic procedures lend
      themselves well to preoperative planning for blood loss. Since total joint
      arthroplasty can be associated with large volume blood loss, planning to replace
      lost blood is mandatory. Allogeneic, designated (or directed) donor, and
      autologous blood transfusion have been the standard of practice for blood
      replacement until very recently. Epoetin alfa, an FDA-approved treatment for
      anemia, can be administered perioperatively to total joint arthroplasty patients
      to help prevent the necessity of postoperative transfusion. Inspired by the
      infection risk associated with allogeneic blood transfusion, this development
      represents a growing trend in perioperative blood management of the orthopaedic
      patient.

PMID- 9526416
TI  - BBA97: the first waves of change.

PMID- 9526417
TI  - The clinician as patient advocate.
AB  - This article presents alternative strategies to traditional methods of patient
      advocacy. These alternative strategies are designed to improve the quality of
      patient care by appealing to the clinician's sense of ethical reasoning and
      responsibility rather than being strictly driven by the legal system. The author
      appeals to the clinician to effect an organization that encourages professional
      debate, promotes client:clinician communication, and builds an ethical culture
      within the workplace. By acknowledging patient's rights, clinician's duty, and
      institutional responsibility, clinician's are better prepared to engage in
      behaviors that encourage trust and collaboration between one another and their
      clients.

PMID- 9526419
TI  - The Ostomy Assessment Inventory: a data-gathering process to enhance appropriate
      pouching system selection.
AB  - Due to the dramatic changes occurring in our healthcare delivery system, many
      levels of care providers across the care continuum are challenged with the task
      of recommending pouching systems for ostomy patients. Selecting a pouch can often
      be a costly process and can prolong rehabilitation. Experience and research shows
      that certain data relating to the patient's performance capabilities, physical
      and psychological status, and patterns of daily living merged with the
      individual's personal preferences, are the infrastructure needed to select
      appropriate pouching systems for patients. A tool was developed to establish a
      standard data collection format for ostomy assessment; to provide the non
      specialized care provider the necessary assessment criteria needed for pouch
      selection, and to serve as a communication tool.

PMID- 9526418
TI  - Civil claims relating to pressure ulcers: a claimants' lawyer's perspective.
AB  - This article addresses attorneys' evolving views of civil claims against nursing
      homes, hospitals, nurses and doctors relating to pressure ulcers. The author
      describes measures that healthcare professionals may take to avoid becoming
      subject to claims, such as properly documenting assessments of patient risks and
      documenting consistent and appropriate care. Several issues of ethical
      consideration for nurses are presented relating to the role of nurses as patient
      advocates, including the issue of under what circumstances may or should a nurse
      recommend that a patient confer with an attorney. The article describes some
      common misconceptions about nursing and medical malpractice claims, and
      identifies ways that some proposed tort reforms appear borne of unsubstantiated
      fears.

PMID- 9526420
TI  - Interface pressure, wound healing, and satisfaction in the evaluation of a non
      powered fluid mattress.
AB  - In this study, a non-powered fluid mattress (hereafter referred to as study
      mattress) was evaluated in terms of interface pressure, wound healing, and
      patient/practitioner satisfaction. The study was divided into two parts. Twenty
      two (22) volunteers placed on the study mattress were used to evaluate interface
      pressure. Pressure ulcer healing and cost of study mattress were evaluated for 36
      stage I-IV pressure ulcers and 24 surgically repaired ulcers in 33 consecutively
      recruited patients. Additionally, patient and practitioner satisfaction with the
      support surface was assessed at the completion of the study. Direct comparison of
      interface pressures with air-fluidized and low-air-loss beds indicate that the
      study mattress relieves pressure as well as existing technology. Wounds of
      patients on the study mattress healed at an average rate of 31 percent per week
      (median 25 percent per week) and flapped wounds healed an average of 7.7 weeks.
      No new ulcers occurred among patients using the study mattress. Both patients and
      practitioners reported satisfaction with the comfort and performance of the study
      mattress and felt it compared favorably with air-fluidized and low-air-loss
      technologies.

PMID- 9526422
TI  - Complications with urinary catheters.

PMID- 9526421
TI  - ASPMN position statement use of placebos for pain management. American Society of
      Pain Management Nurses.

PMID- 9526423
TI  - Infection control.

PMID- 9526424
TI  - Long-term catheter care.

PMID- 9526426
TI  - [Where lies the future of nursing? Changes in professional practice].

PMID- 9526427
TI  - ['Discussion should not be drawing-room talk for the in-group'. Need-oriented
      choice or diagnosis-oriented option?].

PMID- 9526425
TI  - [Nurses' mission 1898-1998].

PMID- 9526428
TI  - [Nursing practice demands more than only diagnosis--ally or specialist?].

PMID- 9526429
TI  - ['Allow more room for decisions to professional practitioners'].

PMID- 9526430
TI  - ['Master plans will differ per field and per care category'--future scenarios on
      the table].

PMID- 9526431
TI  - [Free exchange of persons has limitations--the European labor market for
      nursing].

PMID- 9526432
TI  - [New indications 'objective, integral and independent'. Regional indication
      organs in the starting blocks].

PMID- 9526433
TI  - ['It is especially a question of attentive and systematic working'--new manual
      cytostatics].

PMID- 9526434
TI  - [Infection prevention sometimes conflicts with patient privacy. Protocol for
      needle injuries].

PMID- 9526435
TI  - ['You have to sign in even before hanging your coat'. Time registration for
      district and geriatric care using a barcode reader].

PMID- 9526437
TI  - [Diagnosis in nursing--life style and care systems].

PMID- 9526436
TI  - [Contact between patient and nurse gains in depth and quality by adopting a
      different attitude. Surprise as a professional standard].

PMID- 9526438
TI  - [NANDA, NIC and NOC on the road to a single concept. Professional innovation or a
      clash of interests?].

PMID- 9526439
TI  - [Greater influence nursing on organizational policy'. Role of nursing advisory
      councils].

PMID- 9526440
TI  - Turf wars and curriculum change.

PMID- 9526441
TI  - Further reflections on dying.

PMID- 9526442
TI  - Should private practitioners be paid for teaching?

PMID- 9526443
TI  - The need for Spanish-language training at UCLA.

PMID- 9526445
TI  - The "computer initiative" at Case Western.

PMID- 9526444
TI  - Perceived racial prejudice in medical education.

PMID- 9526446
TI  - Assisting residents with career decisions.

PMID- 9526447
TI  - Admission of Asian Americans to U.S. medical schools.

PMID- 9526448
TI  - I love this job: notes of an internal medicine chairman.

PMID- 9526449
TI  - Affirmative action in medical education: a legal perspective.
AB  - The use of affirmative action programs as part of the effort to increase the
      presence of minorities in medical education and the physician workforce has come
      under greater legal scrutiny. The authors describe the history of the legal
      theory behind affirmative action, giving examples from the evolving case law and
      from Department of Education guidelines. They identify legal pitfalls in the
      areas of admission and financial aid, including the categorization of students by
      race, racially disproportionate financial aid awards after accounting for need,
      racially disproportionate amounts of scholarships as opposed to loans, and, for
      public medical schools, differential treatment of out-of-state students based on
      race. Medical schools should be aware of this legal framework so that they can
      construct affirmative action programs that comply with the law while maintaining
      momentum toward diversification.

PMID- 9526450
TI  - Extending the pipeline for minority physicians: a comprehensive program for
      minority faculty development.
AB  - Medical schools must become more successful in training minority faculty.
      Minority faculty development programs at schools of medicine must involve
      trainees from the undergraduate years (if not before) through junior faculty and
      must involve MD and combine-degree (MD-PhD) students. The authors describe the
      comprehensive minority faculty development program at the University of
      Pennsylvania School of Medicine, which involves minority undergraduates, medical
      students, residents, fellows, and faculty. This program provides the
      administrative staff and research methodologists to assist trainees at all levels
      across all departments in the school of medicine. The principal student
      recruitment program is the undergraduate premedicine enrichment program. The
      medical student component provides general counseling, research development, and
      activities to enhance performance in the clinical courses. The components for
      advanced trainees (residents, fellows, and postdoctoral trainees) and faculty
      consist of training in research methods, mentoring, teaching skills, and
      scientific writing skills. Through this program, the University of Pennsylvania
      School of Medicine has increased the number of under-represented minority faculty
      by 32% since 1993-94 and created an environment conducive to the professional
      growth and development of minority faculty.

PMID- 9526452
TI  - Medical students' evaluations of curriculum innovations at ten North American
      medical schools.
AB  - The authors recount medical educators' calls in the 1980s to reform general
      professional medical education by supplementing the standard lecture-lab
      biomedical curriculum with new biopsychosocial pedagogy and emphases. They then
      report selected medical students' evaluations of corresponding curriculum reform
      efforts that were in place by 1990 at eight U.S. and two Canadian medical schools
      known for being innovators. From interviews conducted in 1992-93 with a group of
      three to nine medical students at each school, the authors report two findings.
      First, the students' positive evaluations converged: at all ten schools they
      invariably appreciated curriculum reform efforts of any sort that encouraged
      individuation, connection, and diversity. Second, the students' negative
      evaluations diverged: specifically, those enrolled at the smaller schools with
      more distinctly teaching-service missions, schools where innovation was more
      wholesale, even extending across the entire curriculum, objected to curricula
      that provide too much in the way of new pedagogy and emphases and too little
      standard instruction; conversely, those enrolled at the larger schools with more
      comprehensive teaching-research-service missions, schools where innovation must
      be more piecemeal, often course by course, objected to curricula that provided
      too little in the way of new pedagogy and emphases and too much standard
      instruction. Suggesting that the smaller schools studied may be over
      supplementing--and the larger schools under-supplementing--standard biomedical
      with new biopsychosocial pedagogy and emphases, the authors make two
      recommendations: first, that medical educators at schools of every size and sort
      contemplating curriculum reform of any scope recognize that medical students
      invariably appreciate educational opportunities for individuation, connection,
      and diversity; second, that the same educators, but especially those at the
      smaller teaching-service medical schools considering more wholesale innovation,
      recognize that medical students must soon compete for residencies and posts in a
      rapidly changing health care environment and thus want effective instruction per
      se, whether it be delivered by a lecturer or a tutor, in class or in tutorial, on
      a ward or in a clinic. That would be the meaning, they conclude, of student
      centered learning, however it were tailored.

PMID- 9526451
TI  - Sustaining the development of primary care in academic medicine. Working Group on
      Sustaining the Development of Academic Primary Care. Association of American
      Medical Colleges.
AB  - This article is the report of the Working Group on Sustaining the Development of
      Academic Primary Care, one of the six subgroups of the Advisory Panel on the
      Mission and Organization of Medical Schools (APMOMS) sponsored by the Association
      of American Medical Colleges (AAMC). To begin, the group draws a distinction
      between primary care and generalism. Primary care is a core domain of health care
      and, in the context of emerging integrated systems, will increasingly be a
      multidisciplinary shared function. Non-subspecialized physicians, or
      "generalists," are a key element in the provision of primary care, but do not act
      alone. Core competencies for primary care are central to the education of all
      physicians. Therefore, irrespective of workforce goals for generalist physicians,
      primary care should have a strong, central position in the medical school so that
      graduates can receive a sound general medical education and can be prepared for
      any specialty and for lifelong learning in an evolving health care system. For
      primary care to achieve that position, medical schools must integrate primary
      care into their missions, strategic plans, operation, organization, academic
      administrative structures, curriculum development, faculty development (both
      school- and community-based), resource development, alliances with appropriate
      clinical services networks, financial policy, and evaluation and educational
      monitoring systems. The group briefly describes the elements of those changes and
      also proposes ways that the AAMC and medical school leaders could promote the
      central role of primary care in medical schools.

PMID- 9526453
TI  - Successful peer review of courses: a case study.
AB  - The authors describe their school's system of peer review for courses,
      established in 1988 to facilitate faculty evaluation and continual course and
      curriculum improvement. (The system has been temporarily suspended while the
      school's new curriculum becomes established.) They explain how the system was
      created and then report how faculty reviews of courses over the five-year
      operation of the system compared with students' reviews of the same courses. The
      faculty and students' ratings were in agreement 75% of the time. When not in
      agreement, the students' ratings tended to upgrade courses that were not very
      demanding, had easy grading, and emphasized clinical details, often at the
      expense of basic concepts and the big picture. The authors then document how the
      work of the peer review system favorably influenced the transformation of the
      school's curriculum. They also provide guidelines for the creation and operation
      of a course review process that uses faculty peers. The authors maintain that the
      peer review system worked because it was run by a committee of experienced and
      respected teachers who had been selected by their peers, the other faculty.
      Additional reasons for its success were that the school's faculty supported and
      respected the committee and its work, that course directors helped evaluate their
      courses, and that peer reviewers took their work seriously despite having no
      remuneration, and the clearly positive impact of the review system on faculty
      interaction, faculty-student interaction, and the reform of the curriculum.

PMID- 9526454
TI  - Service-learning: community-campus partnerships for health professions education.
AB  - In 1995, the Health Professions Schools in Service to the Nation (HPSISN) program
      was launched under the auspices of the Pew Health Professions Commission as a
      national demonstration of an innovative form of community-based education called
      service-learning. The foundation of service-learning is a balanced partnership
      between communities and health professions schools and a balance between serving
      the community and meeting defined learning objectives. This article offers a
      definition of service-learning and an outline of its core concepts; it also
      describes how service-learning differs from traditional clinical education in the
      health professions. Further, the author discusses how service-learning programs
      may benefit students, faculty, communities, higher education institutions, and
      the relationships among all these stakeholders. The article concludes with brief
      descriptions of recommended resources for integrating service-learning into the
      medical school curriculum.

PMID- 9526455
TI  - Creating the practice-learning environment: using information technology to
      support a new model of continuing medical education.
AB  - Many of the traditional approaches to providing continuing medical education
      (CME) have failed to improve physician performance and health care outcomes. In
      the current health care environment, physicians are being held to unprecedented
      levels of accountability to patients, payers, and society at large. A greater
      emphasis is being placed on measuring and improving the clinical and fiscal
      outcomes of medical care. If they are to help physicians practice more
      effectively and efficiently, CME developers must reformulate the missions and
      goals of their programs. CME must become a means for improving patient outcomes
      through enhanced physician performance. The author describes how a new practice
      learning model for CME might be implemented using currently available information
      technology. She also discusses how CME programs, with the help of information
      technology, can help physicians identify learning opportunities, find the best
      resources for learning, and apply learning to practice. She then briefly
      discusses three programs that have begun to utilize information technology to
      expand the scope of CME: the Maintenance of Competence Program in Canada, the
      Stanford Health Information Network for Education, and a computer-simulation
      program at the Indiana University School of Medicine.

PMID- 9526456
TI  - Precollege enrichment programs intended to increase the representation of
      minorities in medicine.
AB  - The authors reviewed the literature published from 1966 to 1996 to identify
      enrichment programs for underrepresented minority precollege students sponsored
      by medical schools and affiliated programs, finding 19 articles describing 27
      programs. The authors categorized the reported programs according to the
      components they contained. Most programs contained more than one component type.
      Twenty-four programs had an academic enhancement component. Two thirds had a
      motivational component to encourage students to consider medical and other health
      careers. Two programs set up mentoring relationship between students and health
      professionals. There were four research apprenticeships and three academic
      partnerships between medical schools and local school districts. Twelve of the 27
      programs were evaluated in the literature. Eight evaluations focused on
      identifying the numbers of students who continued their education into college
      and professional schools. Five programs reported participant satisfaction or
      identified other short-term outcomes such as gains on standardized tests. While
      the percentage of participants completing college and entering health care
      careers is impressive, the authors do not believe that the educational success of
      participants can be attributed to involvement in these programs. The authors
      recommend ways to improve the quality and interpretability of enrichment program
      evaluations. Evaluators should adopt common terminology for activities and
      outcomes. Participants' economic and educational disadvantages should be
      described. Programs' theoretical underpinnings should be identified and related
      to evaluation. Measures should include immediate effects as well as long-term
      outcomes. Where possible, data from comparison groups should be reported to
      support conclusions. Adequate funding needs to be available to design and
      complete reasonable evaluations.

PMID- 9526457
TI  - Enrichment programs for undergraduate college students intended to increase the
      representation of minorities in medicine.
AB  - The authors reviewed the literature published from 1966 to 1996 to identify
      enrichment programs for underrepresented minority college students sponsored by
      medical schools and affiliated programs, finding 20 such programs. The programs
      reported in the literature underestimate the number and variety of programs known
      to exist by about two thirds. The authors categorized the reported programs
      according to the types of components they contained. Most programs contained more
      than one component type. Eighteen of the programs had an academic enrichment
      component. Thirteen programs included components focused on preparation for the
      admission process. Mentoring activities were a component of only four of the
      programs. Eighteen of the 20 programs were evaluated in the literature. The
      largest focus of evaluation activities was the success of program participants
      entering medical school. While the medical school matriculation rate was quite
      high, these results were difficult to interpret as the studies did not use
      control groups. The evaluations could not demonstrate, therefore, that the
      programs were responsible for increased admission of minorities to medical
      schools. Relatively few studies measured the immediate effects of the programs'
      efforts. Further, there was even less evidence of which program components in
      particular were effective. A more public and energetic discussion of these
      programs in the medical education literature is essential. In a political and
      social environment that calls for accountability, programs must be able to
      clearly and truthfully declare what they have accomplished. Without this type of
      public discussion, enrichment programs for underrepresented minorities may
      continue to appear to be worthwhile endeavors, but lacking solid support and
      foundation and vulnerable to losing funding.

PMID- 9526458
TI  - Factors influencing the career choices of physicians trained at Yale-New Haven
      Hospital from 1929 through 1994.
AB  - PURPOSE: To examine factors that influenced, positively or negatively, the
      specialty career choices of physicians trained at Yale-New Haven Hospital (YNHH)
      from 1929 to 1994. METHOD: The authors sent questionnaires to 4,888 physicians
      who had trained or were training in YNHH-sponsored residency programs. The
      physicians rated 36 factors posited to be influenced in career choice on a seven
      point Likert scale from very negative to very positive. The authors compared the
      means of each factor's ratings by decade of medical school graduation. RESULTS:
      The most positively rated influences were similar in each decade from the 1920s
      to the 1990s. These influences shared characteristics of intellectual curiosity
      ("intellectual content of the specialty" and "challenging diagnostic problems"),
      altruism ("interest in helping people" and "opportunity to make differences in
      people's lives"), and personal identity ("consistent with personality" and
      "possess the required skill or ability"). Negative factors, such as "demands on
      time and effort," "stress in the field," and "malpractice costs," were also
      consistently rated throughout the decades. CONCLUSION: The reasons that
      physicians choose certain specialty careers have not changed significantly over
      the past 65 years despite all the changes that have occurred in medicine.
      Physicians continue to seek professional opportunities that are viewed as
      intellectually challenging and of benefit to others.

PMID- 9526459
TI  - Junior faculty members' mentoring relationships and their professional
      development in U.S. medical schools.
AB  - PURPOSE: To determine (1) the prevalence of mentoring relationships for U.S.
      medical school junior faculty; (2) the quality of these mentoring relationships;
      (3) any variation by gender or race; and (4) the relationship between mentoring
      and junior faculty members' perceptions of institutional professional support;
      research-, teaching-, and clinical-skills development; allocation of time to
      professional activities; and career satisfaction. METHOD: In 1995 a 177-item
      survey was mailed to 3,013 full-time faculty at 24 randomly selected U.S. medical
      schools stratified on an area of medical specialization, graduation cohort, and
      gender. Mentoring was defined as "dynamic reciprocal relationship between an
      advanced career incumbent (the mentor) and a junior faculty member (the protege)
      aimed at fostering the development of the junior person/protege." Because
      mentoring is most crucial for junior faculty, the study focused on mentoring
      relationships within the previous three years ("recent mentoring") for faculty
      who were not full professors. Chisquare tests, analysis of variance, and
      principal-components analysis were used to analyze the data. RESULTS: In all,
      1,808 (60%) of the 3,013 faculty surveyed, of whom 72% were junior faculty,
      returned completed questionaires. Fifty-four percent of the junior faculty had
      had a recent mentoring relationship. There was no significant difference between
      the men and the women faculty or between majority and minority faculty in the
      prevalence and quality of the mentoring relationships. The faculty with mentors
      rated their research preparation and research skills higher than did the faculty
      without mentors. Most of the women faculty (80%) and the minority faculty (86%)
      who had had mentors reported that it was not important to have a mentor of the
      same gender or minority group. CONCLUSION: Mentoring relationships are prevalent
      in academic medicine and should be promoted to support the career growth of
      junior faculty.

PMID- 9526460
TI  - Beneficial and harmful effects of augmented feedback on physicians' clinical
      teaching performances.
AB  - PURPOSE: To evaluate whether clinical-teaching skills could be improved by
      providing teachers with augmented student feedback. METHOD: A randomized,
      controlled trial in 1994 included 42 attending physicians and 39 residents from
      the Department of Medicine at the Indiana University School of Medicine who
      taught 110 students on medicine ward rotations for one-month periods. Before
      teaching rotations, intervention group teachers received norm-referenced, graphic
      summaries of their teaching performances as rated by students. At mid-month,
      intervention group teachers received students' ratings augmented by
      individualized teaching-effectiveness guidelines based on the Stanford Faculty
      Development Program framework. Linear models were used to analyze the students'
      mean ratings of teaching behaviors at mid-month and end-of-month. Independent
      variables included performance ratings, intervention status, teacher status,
      teaching experience, and interactions with baseline ratings. RESULTS: Complex
      interactions with baseline performance were found for most teaching categories at
      mid-month and end-of-month. The intervention-group teachers who had high baseline
      performance scores had higher student ratings than did the control group teachers
      with similar baseline scores; the intervention group teachers who had low
      baseline performance scores were rated lower than were the control group teachers
      with comparable baseline scores. The residents who had medium or high baseline
      scores were rated higher than were the attending physicians with comparable
      baseline scores; the performance of the residents who had low baseline scores was
      similar to that of the attending physicians with comparable baseline scores.
      CONCLUSION: Baseline performance is important for targeting those teachers most
      likely to benefit from augmented student feedback. Potential deterioration in
      teaching performance warrants a reconsideration of distributing students' ratings
      to teachers with low baseline performance scores.

PMID- 9526461
TI  - Critical success factors for promotion and tenure in family medicine departments.
AB  - PURPOSE: (1) To summarize the judgments of family medicine department leaders
      regarding the elements leading to success in promotion and/or tenure, and (2) to
      compare the views of department leaders with those of family medicine faculty who
      have been successfully promoted. METHOD: Two surveys were conducted. The first
      was of 296 associate professor members of the Society of Teachers of Family
      Medicine in November 1993. The second, conducted in the summer of 1994, was of
      all 115 U.S. members of the Association of Departments of Family Medicine;
      surveys were addressed to chairs, directors, or promotion and tenure committee
      chairs. Both survey instruments requested data regarding each respondent's
      department, impressions about the promotion and tenure processes at the
      respondent's institution, and general impressions regarding the characteristics
      of successful candidates. Comparisons of the responses to the two questionnaires
      were made using two-tailed t-tests; responses to open-ended questions were
      analyzed qualitatively by two independent investigators. RESULTS: In all, 75% of
      the department leaders and 67% of the associate professors returned completed
      questionnaires. The two groups had similar views about the importance of certain
      academic activities to success at promotion and tenure. The primary difference
      between the groups was in their estimates of weekly time available for research
      and writing activities: the leaders reported that successful candidates spent a
      mean of 25% of their work-weeks on research and writing activities; the associate
      professors, on the other hand, reported spending a mean of 15% of their workweeks
      on these activities. The department leaders described six basic groups of
      critical success factors. The associate professors emphasized lack of time as a
      major obstacle to success. CONCLUSION: The findings emphasize the critical
      importance of protected time for scholarly activities (such as research and
      writing) if generalists are to be promoted or tenured.

PMID- 9526462
TI  - Attrition rates of underrepresented minority students at the University of
      Illinois at Chicago College of Medicine, 1993-1997.
AB  - PURPOSE: To examine the attrition rates of underrepresented minority (URM)
      students and non-URM students at the University of Illinois at Chicago's College
      of Medicine (UIC-COM). METHOD: The study used 11 categories of information about
      URM and non-URM students at UIC-COM for the five academic years 1993-1997 to
      determine how many students withdrew and why. RESULTS: Of 895 graduates during
      these five years, 166 (18.5%) were URM students. The attrition rates were 6.5%
      for all graduates, 16.2% for URM students, and 4.0% for non-URM students.
      Students who withdrew because of academic difficulties comprised 75% of URM
      withdrawals and 57% of non-URM withdrawals. CONCLUSION: Many URM students need
      special academic attention after matriculation. Existing academic support
      programs should be assessed regularly to ascertain whether they may be improved
      to minimize attrition.

PMID- 9526463
TI  - What hysterectomy [corrected] patients want to know about the roles of residents
      and medical students in their care.
AB  - PURPOSE: To determine what patients want to know regarding the participation of
      trainees in their care. METHOD: In 1995, questionnaires were sent to 111 women
      who had undergone elective hysterectomies between September 1992 and June 1994 at
      two teaching hospitals at the University of California, San Francisco, School of
      Medicine. The questionnaires asked the women about their awareness of and
      attitudes toward the participation of residents and medical students in their
      care and about how they thought physicians should communicate information
      regarding residents to patients. RESULTS: Fifty-nine women (68%) returned the
      questionnaire. Thirty-seven of them (63%) knew that a resident had been involved
      in their care. Eighty percent of the respondents felt it important to know how
      residents were supervised and what they would do during the operation. Nearly
      half did not know whether a medical student had been involved in their care. Over
      90% agreed that the attending gynecologist should tell patients that a resident
      would participate in the operation as well as what the resident would do. Most
      believed that residents are adequately supervised and that medical students have
      time to provide more attention to patients. CONCLUSIONS: Most of the women wanted
      to know about the participation and specific roles of residents and students.
      Attending physicians should take the initiative to talk with patients about the
      roles of trainees. Open discussions can promote patient autonomy, maintain public
      confidence in academic health institutions, and benefit future patients.

PMID- 9526465
TI  - Blood transfusions: listen to the patient.

PMID- 9526464
TI  - Are medical students ready to provide HIV-prevention counseling?
AB  - PURPOSE: To determine whether medical students were prepared to assess risk and
      counsel patients about prevention of HIV infection, and whether HIV-related
      experience produced better knowledge and counseling skills. METHOD: In 1995,
      students at four North Carolina medical schools interviewed a standardized
      patient portraying a young woman concerned about HIV infection. The standardized
      patient recorded whether students asked risk-behavior questions and provided risk
      reduction advice. A 21-item questionnaire assessed the students' knowledge of HIV
      testing and prevention. Students indicated whether they had had experience in
      educational settings related to HIV or STDs. RESULTS: 415 students completed both
      the patient interview and the questionnaire. Many failed to ask the patient about
      several HIV-risk behaviors. Although nearly all (98%) inquired about condom use,
      fewer than two thirds asked about the patient's history of STDs, number of sexual
      partners, or specific sexual practices. Most students advised the patient to use
      condoms. The average score on the knowledge test was 79%; 70% of students
      confused anonymous with confidential testing, more than half overestimated the
      risk of HIV transmission from a needle stick, and nearly one in ten did not know
      how to use a condom. Educational exposures did not produce significantly better
      risk assessment, counseling information, or knowledge scores. CONCLUSION: A
      majority of experienced medical students did not assess several important risk
      factors of a patient concerned about HIV infection, and many would have provided
      incorrect information related to HIV testing and prevention of infection. Patient
      contact in traditional clinical settings did not influence prevention knowledge
      or behavior. More innovative methods are needed to train students in HIV
      infection prevention and counseling.

PMID- 9526466
TI  - Was an 8-hour wait really unreasonable?

PMID- 9526467
TI  - Address unknown--or at least uncertain.

PMID- 9526468
TI  - Debating the management of osteoporosis risk.

PMID- 9526469
TI  - Follow-up after endometrial cancer.

PMID- 9526470
TI  - Follow-up after endometrial cancer.

PMID- 9526471
TI  - Follow-up after endometrial cancer.

PMID- 9526472
TI  - Discrimination against gay, lesbian and bisexual family physicians by patients.
AB  - BACKGROUND: Discrimination against gay, lesbian and bisexual (GLB) patients by
      physicians is well known. Discrimination against GLB physicians by their
      colleagues and superiors is also well known and includes harassment, denial of
      positions and refusal to refer patients to them. The purpose of this study was to
      identify and quantify the attitudes of patients toward GLB physicians. METHODS:
      Telephone interviews were conducted with 500 randomly selected people living in a
      large urban Canadian city. Subjects were asked if they would refuse to see a GLB
      family physician and, if so, to describe the reason why. They were then given a
      choice of 6 reasons obtained from consultation with 10 GLB people and 10
      heterosexual people. RESULTS: Of the 500 subjects 346 (69.2%) were reached and
      agreed to participate. Of the 346 respondents 41 (11.8%) stated that they would
      refuse to see a GLB family physician. The 2 most common reasons for the
      discrimination (prevalence rate more than 50%) were that GLB physicians would be
      incompetent and the respondent would feel "uncomfortable" having a GLB physician.
      Although more male than female respondents discriminated against GLB physicians,
      the difference was not statistically significant. The proportion of male and
      female respondents who discriminated increased with age (p < 0.01). CONCLUSIONS:
      The observed prevalence of patient discrimination against GLB family physicians
      is significant. The results suggest that the discrimination is based on emotional
      reasons and is not related to such factors as misinformation about STDs and fear
      of being thought of sexually. Therefore, educational efforts should be directed
      against general perceptions of homosexuality rather than targeting specific
      medical concerns.

PMID- 9526473
TI  - Tuberculosis among immigrants: interval from arrival in Canada to diagnosis. A 5
      year study in southern Alberta.
AB  - OBJECTIVE: To examine the pattern of tuberculosis (TB) occurring among immigrants
      and the interval from arrival in Canada to diagnosis of the disease. DESIGN:
      Study of all cases of TB diagnosed in foreign-born residents of southern Alberta
      during the 5-year period 1990-1994. SETTING: A centre for the diagnosis,
      management and control of all cases of TB in the southern half of the province of
      Alberta. METHODS: All foreign-born patients in whom TB was newly diagnosed
      between January 1990 and December 1994 were included in the study. The interval
      from their arrival in Canada to diagnosis, their country of birth and the site of
      their disease were documented. RESULTS: Immigrants to Canada accounted for 248
      (70.6%) of the 351 cases of TB diagnosed in southern Alberta during the 5-year
      period. The majority of these immigrants (182/248 [73.4%]) were of Asian origin.
      Extrapulmonary TB accounted for 111 (61.0%) of the 182 cases of the disease in
      Asian immigrants. The mean period between immigration and diagnosis was 11.2
      years (standard deviation [SD] 13.9 years). Half of the patients presented within
      7 years of their arrival in Canada. The time to presentation was shortest for
      patients with superficial lymph node disease (mean 7.6 years [SD 6.9] after
      arrival), intermediate among those with extrapulmonary disease, excluding
      superficial disease of the lymph node (10.1 years [SD 12.1]), and longest for
      those with pulmonary disease (14.2 years [SD 17.2]). TB developed sooner after
      arrival in Canada among immigrants from Asian countries (mean 9.1 years) than
      among those from other countries (17.2 years) (p = 0.01). CONCLUSIONS: Given the
      low annual incidence of TB in Canada (7.1 per 100,000), it is probable that TB
      occurring among immigrants reflects infection acquired before arrival in Canada.
      Health care professionals need to be aware that immigrants from countries with a
      relatively high prevalence of TB remain at risk for the disease (often at an
      extrapulmonary site) for many years after they immigrate to low-prevalence
      countries.

PMID- 9526474
TI  - Epidemiology of tuberculosis in Montreal.
AB  - OBJECTIVE: To identify the epidemiologic characteristics of tuberculosis (TB) in
      Montreal and the patterns of resistance to antituberculous drugs in order to
      improve TB control in the region. DESIGN: Descriptive analysis of surveillance
      data for TB cases reported in Montreal by physicians and laboratories between
      1992 and 1995. SETTING: Region of Montreal, population 1,775,889. PARTICIPANTS:
      All cases of active TB among Montreal residents reported to the Department of
      Public Health between Jan. 1, 1992, and Dec. 31, 1995. OUTCOME MEASURES:
      Epidemiologic characteristics, proportion of cases resistant to antituberculous
      drugs and types of resistance. RESULTS: A total of 798 cases of TB (mean annual
      incidence 11.2 per 100,000) were reported in Montreal during the study period. Of
      these patients, 617 (77.3%) were born outside Canada. The annual incidence of TB
      in the foreign-born population (37.5 per 100,000) was 10 times the rate in the
      Canadian-born population, and the highest rate among foreign-born residents (62.8
      per 100,000) occurred in those 15-29 years of age. In general, annual incidence
      in Montreal's foreign-born population reflected the reported incidence of TB in
      their regions of birth. In 8.7% of all cases, the disease was resistant to
      isoniazid, and the proportion of cases resistant to this drug was greater than 4%
      in almost all age groups, among both foreign-born and Canadian-born patients.
      CONCLUSIONS: TB remains a major problem in Montreal, as in other large cities.
      Surveillance data give opportunities to public health agencies to adapt their
      prevention and control strategies to local situations and can also help
      clinicians in their clinical decision-making.

PMID- 9526475
TI  - Globalization of tuberculosis.

PMID- 9526476
TI  - Sound privacy for patients.

PMID- 9526477
TI  - Statement on project-specific industry support for research. International
      Committee of Medical Journal Editors.

PMID- 9526478
TI  - Should relatives witness resuscitation? Ethical issues and practical
      considerations.
AB  - In winning second prize in the Logie Medical Ethics Essay Contest in 1997,
      Carolyn Rosenczweig raised questions about the role patients' family members
      should be allowed to play during resuscitative efforts by medical staff. She
      concluded that even though their presence might complicate resuscitation
      attempts, "blanket policies that exclude all relatives from being present seem a
      knee-jerk reaction."

PMID- 9526479
TI  - After the strike: using facilitation in a residency training program.
AB  - Methods of alternative dispute resolution, including facilitation, can be used to
      identify and resolve areas of conflict. Facilitation was used by the University
      of Saskatchewan's Department of Family Medicine (Saskatoon division) after the
      strike by residents in July and August 1995 so as to allow optimal use of the
      remaining educational time. Through facilitation, experiences of the strike and
      areas of potential conflict were explored. Participants had a broad range of
      responses to the strike. Specific coping strategies were developed to deal with
      identified concerns. Although outcomes were not measured formally, levels of
      trust improved and collegial relationships were restored. Because so many changes
      occur in health care and medical education, conflict inevitably arises.
      Facilitation offers one way of dealing with change constructively, thereby making
      possible the optimal use of educational time.

PMID- 9526480
TI  - Stereotactic radiosurgery: comparing different technologies.
AB  - Radiosurgery can be defined as 3-dimensional stereotactic irradiation of small
      intracranial targets by various radiation techniques. The goal is to deliver,
      with great accuracy, a large, single fraction dose to a small intracranial
      target, while minimizing the absorbed dose in the surrounding tissue. This
      article describes certain technical aspects of radiosurgery and compares the
      different methods of performing such treatment. The 2 most frequently used types
      of devices for radiosurgery are units with multiple cobalt sources (e.g., the
      Gamma Knife) and those based on a linear accelerator. In the former, highly
      collimated beams of radiation from the cobalt sources intersect at the target. In
      the latter, the source of a highly collimated beam of high-energy photons
      directed at the target turns through an arc or set of arcs. The accuracy of
      target localization, the steepness of fall-off of the radiation dose outside the
      target and the ability to irradiate an irregularly shaped target are all
      comparable for these 2 types of devices, despite claims to the contrary.

PMID- 9526481
TI  - Anthrax.

PMID- 9526483
TI  - Herbal medicine takes root in Germany.
AB  - The sale of Herbal Medicine is a growth industry in Germany, where physicians
      routinely prescribe these products and annual sales have surpassed $ 2 billion.
      Pam Harrison says the rising popularity has been driven by German patients, who
      began demanding herbal alternatives to synthetic drugs. Medical schools responded
      by reintroducing lessons on a topic that had been phased out of the medical
      curriculum.

PMID- 9526484
TI  - Teaching on addiction issues lacking in medical school, specialists told.
AB  - During the 1997 annual scientific meeting of the Canadian Society of Addiction
      Medicine, a medical student complained that medical schools do not provide enough
      education on addiction-related issues. April Boyd said most students want the
      information because they think they will face these issues when they enter
      practice.

PMID- 9526485
TI  - Network helps hospitals develop own evidence-based medicine.
AB  - A Research Network Based in London, Ont., aims to improve hospital care by having
      hospitals share information. The research points out the ways some hospitals do
      things differently. Dr. William Sibbald, who heads the network, says that if
      hospitals overcome some of the variations between them, they may be "able to save
      money and become more efficient."

PMID- 9526486
TI  - User-friendly approach lets hospital reach out to disaffected youth.

PMID- 9526487
TI  - Surfing the Net for health care help.

PMID- 9526489
TI  - [Long term results of treatment of highly-malignant non-Hodgkin lymphoma in the
      elderly (70 years and older)].
AB  - OBJECTIVE: To assess retrospectively the results of long-term combined
      chemotherapy and radiotherapy of patients 70 years of older, taking into account
      the international non-Hodgkin lymphoma (NHL) prognostic index of Shipp as well as
      the dose-intensity. PATIENTS AND METHODS: Of 303 patients treated for aggressive
      NHL 100 were aged 70 years or more (median age 76 years). Localized stages I or
      II were present in 56, advanced stages III or IV in 44, and 38 had extranodal
      tumours. 92 patients were given multiple-drug chemotherapy according to the CHOP
      or COP BIAM protocols (n = 89 and 3, respectively), followed by single large
      field or "involved field" radiotherapy with the aim of consolidation (n = 49) or
      cure (n = 26). RESULTS: Recurrence-free and total survival probabilities were 32%
      and 30%, respectively. 54 patients with stages I or II survived 10 years, but
      only six survived just 4 years with stages III or IV. There were five treatment
      associated deaths. INTERPRETATION: Combined chemo- and radiotherapy can achieve
      long-term remission in most even elderly patients with localized stages of
      aggressive NHL.

PMID- 9526490
TI  - [Evaluation of the function of the tubular esophagus in patients with progressive
      systemic scleroderma based on a standardized symptom score].
AB  - BACKGROUND AND OBJECTIVE: The oesophagus is the internal organ most often
      affected in progressive systemic scleroderma (PSS). Suitable methods for
      demonstrating oesophageal involvement are available in only a few centres. Aim of
      this study was to validate a standardized symptom score for assessing oesophageal
      function in patients with PSS. PATIENTS AND METHODS: Oesophageal symptoms of
      dysphagia, odynophagia (pain on swallowing), heartburn and regurgitation were
      assessed in 27 consecutive patients with PSS. Intensity (0 to 3 points) and
      frequency (1 to 4 points) of these symptoms were quantified using a standardized
      system (after de Dombal and Hall): points per symptom (0 to 12) and points per
      patient (0 to 48). Results were compared with long-term manometric recordings as
      reference. The control group consisted of 20 healthy volunteers matched for age
      and sex. RESULTS: Healthy controls and patients with PSS had significantly
      different oesophageal motility: 22 of 27 patients fulfilled the criteria of
      oesophageal hypomotility. Using a total symptoms score of 8 points (points per
      patient) as limit of normal, the sensitivity of the scoring for the diagnosis of
      abnormal oesophageal function was 68%, with a specificity of 100%, positive
      predictive value of 100% and a negative predictive value of 42%. INTERPRETATION:
      The reported method of symptom scoring provides a valid means of positive
      prediction of (abnormal) oesophageal function, making manometric investigation
      unnecessary. Absence or an only mild degree of oesophageal symptoms does not
      exclude abnormal motility so that manometry must be performed in such patients.

PMID- 9526491
TI  - [Late manifestation of a fatal Behcet's disease with cardiac involvement and
      lethal outcome].
AB  - HISTORY AND CLINICAL FINDINGS: One year before admission a 67-year-old man of
      German origin developed extensive ulcerations of the limbs, later also of the
      trunk and neck. In addition to recurrent oral aphthous ulcers it was associated
      with erythema nodosum and intermittent arthritis of the elbow knee and ankle
      joints. During the last month he also had dyspnoea. Echocardiography revealed a
      dilated cardiomyopathy (DCM). He was admitted because of the progressive skin
      disorder. Physical examination showed a disoriented man with dyspnoea, cyanosis
      of the lips and pretibial oedema. He had aphthous ulcers in the mouth and on the
      genitals. Adamant Behcet disease was suspected. INVESTIGATIONS: Erythrocyte
      sedimentation rate was raised to 21/48 mm/h, white cell count to
      15,800/microliter. Tests for HLA B5 and B27 were negative, skin biopsy revealed
      superficial necrotizing vasculitis of postcapillary venules. TREATMENT AND
      COURSE: Initially high doses of prednisolone, 100 mg/d intravenously) and
      azathioprine (100 mg/d orally) were administered, and within a few days both the
      skin and cardiac changes had regressed. Prednisolone dosage was reduced and
      cyclosporin (350 mg/d) substituted for azathioprine. He was discharged in a
      markedly improved general condition and with only a few tibial ulcerations. 4
      months later he had a severe recurrence with dramatic mucocutaneous involvement
      and rapidly deteriorating DCM, together with radiological signs of pneumonia. He
      died 4 months later. INTERPRETATION: Although very rare, Behcet disease should
      even in the elderly patients be considered in the differential diagnosis: in the
      presence of appropriate symptoms cardiac involvement should be looked for.

PMID- 9526492
TI  - [Diagnosis of acute pulmonary embolism].

PMID- 9526493
TI  - [Pathogenicity factors of bacterial disease agents].

PMID- 9526494
TI  - ["Alcoholic" liver damage in nonalcoholics: nonalcoholic steatohepatitis].

PMID- 9526495
TI  - Ca2+/phospholipid-binding (C2) domain in multiple plant proteins: novel
      components of the calcium-sensing apparatus.

PMID- 9526496
TI  - A -308 deletion of the tomato LAP promoters is able to direct flower-specific and
      MeJA-induced expression in transgenic plants.
AB  - Tomato and potato leucine aminopeptidase (LAP) mRNAs are induced in response to
      mechanical wounding and the wound signal molecules, ABA and jasmonic acid. Here,
      we report the isolation of two LAP genes, LAP17.1A and LAP17.2, from tomato.
      Functional analysis in transgenic tomato and potato plants show that fusions of
      the corresponding 5' non-coding regions to the gusA gene are constitutively
      expressed in flowers and induced in leaves upon wounding or by treatment with
      methyl jasmonate (MeJA). Comparison of the 5' non-coding regions of the two genes
      revealed a region from -317 to -3 relative to the ATG, which is strongly
      conserved in both promoters. This 0.3 kb proximal promoter fragment is sufficient
      to direct flower-specific and MeJA-inducible GUS activity in transgenic potato
      plants, and thus contains a MeJA-responsive element that mediates induction by
      MeJA. Dimeric TGACG motifs or G-box elements similar to those found in other MeJA
      inducible genes are not observed in this region, which suggests that a different
      DNA sequence is involved in MeJA induction of the LAP genes.

PMID- 9526497
TI  - Promoter recognition by a cyanobacterial RNA polymerase: in vitro studies with
      the Calothrix sp. PCC 7601 transcriptional factors RcaA and RcaD.
AB  - To study the transcriptional apparatus and the mechanisms that control gene
      expression in cyanobacteria, the RNA polymerase was purified from the filamentous
      Calothrix sp. PCC 7601 and used in in vitro transcription assays. Conditions
      required for specific transcription initiation to occur were analyzed with the
      eleven Calothrix PCC 7601 genes for which the 5' ends have been mapped. Most of
      the transcripts directly obtained did not have the expected size, providing a
      test for looking at specific transcription factors. Addition of RcaA, a protein
      that binds to the promoter region of the phycobiliprotein cpeBA operon, restored
      accurate initiation of transcription in the in vitro system for three
      phycobiliprotein promoters. RcaA thus is a transcription factor that allows to
      mimick in vivo transcription. In parallel, the functional properties of the
      Escherichia coli and cyanobacterial RNA polymerases were compared. The enteric
      enzyme could not precisely initiate transcription at the promoter of a
      phycobiliprotein gene and, reciprocally, the cyanobacterial RNA polymerase could
      initiate transcription at PlacUV5, but not from wild-type Plac promoters. The
      different behaviours of the enzymes are discussed in the light of the structural
      differences that exist between subunits of the RNA polymerases.

PMID- 9526498
TI  - Rice proteins that bind single-stranded G-rich telomere DNA.
AB  - In this work, we have identified and characterized proteins in rice nuclear
      extracts that specifically bind the single-stranded G-rich telomere sequence.
      Three types of specific DNA-protein complexes (I, II, and III) were identified by
      gel retardation assays using synthetic telomere substrates consisting of two or
      more single-stranded TTTAGGG repeats and rice nuclear extracts. Since each
      complex has a unique biochemical property and differs in electrophoretic
      mobility, at least three different proteins interact with the G-rich telomere
      sequences. These proteins are called rice G-rich telomere binding protein (RGBP)
      and none of them show binding affinity to double-stranded telomere repeats or
      single-stranded C-rich sequence. Changing one or two G's to C's in the TTTAGGG
      repeats abolishes binding activity. RGBPs have a greatly reduced affinity for
      human and Tetrahymena telomeric sequence and do not efficiently bind the cognate
      G-rich telomere RNA sequence UUUAGGG. Like other telomere binding proteins, RGBPs
      are resistant to high salt concentrations. RNase sensitivity of the DNA-protein
      interaction. In this assay, we observed a novel complex (complex III) in gel
      retardation assays which did not alter the mobilities or the band intensities of
      the two pre-existing complexes (I and II). The complex III, in addition to
      binding to telomeric sequences, has a binding affinity to rice nuclear RNA,
      whereas two other complexes have a binding affinity to only single-stranded G
      rich telomere DNA. Taken together, these studies suggest that RGBPs are new types
      of telomere-binding proteins that bind in vitro to single-stranded G-rich
      telomere DNA in the angiosperms.

PMID- 9526499
TI  - High-level expression of a viscotoxin in Arabidopsis thaliana gives enhanced
      resistance against Plasmodiophora brassicae.
AB  - Viscotoxins are a group of toxic thionins found in several mistletoe species. The
      constitutive CaMV-omega promoter was used to drive the expression of the
      viscotoxin A3 cDNA from Viscum album in transgenic Arabidopsis thaliana C24.
      Lines with high viscotoxin A3 levels in all parts of the plant were selected and
      tested for resistance against the clubroot pathogen Plasmodiophora brassicae. The
      transgenic lines were more resistant to infection by this pathogen than the
      parental line.

PMID- 9526500
TI  - Cloning of tobacco genes that elicit the hypersensitive response.
AB  - We used a functional screening method to isolate genes whose products elicit the
      hypersensitive response (HR) pathway of defense against plant pathogens. A cDNA
      library derived from tobacco leaves undergoing the HR was cloned into a tobacco
      mosaic virus (TMV)-based expression vector. Infectious transcripts were generated
      and used to inoculate tobacco plants lacking the N resistance gene (genotype
      Xanthi nn). Approximately 1/1000 of the infectious transcripts produced local
      lesions, and may thus elicit the HR. The cDNA inserts from 50 lesion-forming
      clones were recovered by RT-PCR, and 12 unique clones were sequenced. Comparisons
      with protein databases revealed homologies to (a) ubiquitin, (b) tobacco tumor
      related protein, similar to Kunitz-type trypsin inhibitors and (c) ribosomal
      protein S14. The remaining nine clones revealed no homology to known proteins and
      are thus considered novel. Five clones were able to induce the expression of PR2,
      a gene which is specifically activated in the tobacco HR. Northern and western
      blot analyses of leaves infected by the clone encoding ubiquitin strongly suggest
      that the infection produced a co-suppression response; the endogenous level of
      ubiquitin mRNA and protein in infected leaves are ca. 50% less than those found
      in healthy leaves. This observation supports a previous report on the involvement
      of the ubiquitin system in the tobacco HR [2], and validates and utility of the
      functional cloning method.

PMID- 9526501
TI  - NAD(+)-dependent isocitrate dehydrogenase from Arabidopsis thaliana.
      Characterization of two closely related subunits.
AB  - Two cDNA clones which appear to encode different subunits of NAD(+)-dependent
      isocitrate dehydrogenase (IDH; EC 1.1.1.41) were identified by homology searches
      from the Arabidopsis EST database. These cDNA clones were obtained and sequenced;
      both encoded full-length messages and displayed 82.7% nucleotide sequence
      identity over the coding region. The deduced amino acid sequences revealed
      preprotein lengths of 367 residues, with an amino acid identity of 86.1%. Genomic
      Southern blot analysis showed distinct single-copy genes for both IDH subunits.
      Both IDH subunits were expressed as recombinant proteins in Escherichia coli, and
      polyclonal antibodies were raised to each subunit. The Arabidopsis cDNA clones
      were expressed in Saccharomyces cerevisiae mutants which were deficient in either
      one or both of the yeast NAD(+)-dependent IDH subunits. The Arabidopsis cDNA
      clones failed to complement the yeast mutations; although both IDH-I and IDH-II
      were expressed at detectable levels, neither protein was imported into the
      mitochondria.

PMID- 9526503
TI  - The 38 kDa chlorophyll a/b protein of the prokaryote Prochlorothrix hollandica is
      encoded by a divergent pcb gene.
AB  - The chlorophyll (Chl) a/b proteins of the photosynthetic prokaryotes appear to
      have evolved by gene duplication and divergence of the core Chl a antenna family,
      which also includes CP43 and CP47 and the iron-stress induced Chl a-binding IsiA
      proteins. We show here that Prochlorothrix hollandica has a cluster of three pcb
      (prochlorophyte chlorophyll b) genes which are co-transcribed. The major antenna
      polypeptides of 32 and 38 kDa are encoded by pcbA and pcbC respectively. The pcbC
      gene is significantly divergent from the other two and may have originated by a
      gene duplication independent of the one that led to isiA and the other
      prochlorophyte pcb genes. The distant relatedness of the three prochlorophyte
      genera implies that not only the ability to make Chl b and use it for light
      harvesting arose independently in the three lineages, but also that the pcb genes
      may have arisen as the result of independent gene duplications in each lineage.

PMID- 9526502
TI  - Molecular cloning and mRNA localization of tomato pollen profilin.
AB  - The actin cytoskeleton plays an important role in the growth of pollen tube. The
      actin-binding protein profilin could play a role in regulating the organization
      of the actin filaments. Using the RT-PCR technique, we isolated a cDNA clone
      (designated LePro 1) encoding profilin from pollen grains of tomato (Lycopersicon
      esculentum Mill. cv. Moneymaker). Sequence analysis of the insert shows 87%
      similarity to tobacco ntPro2, 78% to timothy grass profilin, 77% to Arabidopsis
      AthPRF4, 77% to maize ZmPro3, and 73% to birch profilin. Both quantitative PCR
      and RNA gel blot analyses demonstrated that LePro 1 is expressed in a tissue- or
      cell-type specific manner in the tomato plant. In situ hybridization of 2 microns
      thick anther sections using a non-radioactive labeling method reveals that LePro
      1 is expressed only in pollen grains, with undetectable transcription in other
      parts of the anther or the other organs. Phylogenetic analysis of amino acid
      sequences of 18 plant profilins indicates that two distinct profilin gene classes
      are present in higher plants. One is pollen-specific, another is constitutive.
      LePro 1 belongs to the former class.

PMID- 9526505
TI  - A higher-plant type zeta-carotene desaturase in the cyanobacterium Synechocystis
      PCC6803.
AB  - The genomic DNA sequence of Synechocystis was analysed for putative zeta-carotene
      desaturase genes. Two promising candidates slr0940 and slr0033 were found with
      similarities to the structurally different zeta-carotene desaturase genes from
      higher plants and Anabaena, respectively. Only the expression product of the
      analogue to the plant gene, slr0940, was able to mediate the 2-step desaturation
      of zeta-carotene via neurosporene to lycopene after complementation of this
      pathway in Escherichia coli. When enzyme reactions were carried out with this
      protein, activity was obtained with either zeta-carotene or neuroporene as
      substrates. The in vitro reaction was inhibited by the pyrimidine derivative J852
      which is effective as experimental herbicide in plants. The occurrence of two
      different types of zeta-carotene desaturases among cyanobacteria and the
      phylogenetic consequences on chloroplast evolution are discussed.

PMID- 9526504
TI  - Molecular characterization of a single mitochondria-associated double-stranded
      RNA in the green alga Bryopsis.
AB  - Mitochondria from the green alga Bryopsis sp. very often contained a 4.5 kb
      double-stranded RNA (dsRNA) at a defined level. Complementary DNA probes derived
      from the mitochondrial dsRNA hybridized with none of the algal chloroplast dsRNAs
      of 1.7 to 2.2 kb, but did hybridize with a similar-sized dsRNA among several
      dsRNAs from the mitochondria of B. maxima. Sequence analysis of the mitochondrial
      dsRNA from Bryopsis sp. revealed only two large, overlapping, open reading frames
      (ORFs) on one strand if UGA was taken as a non-termination codon, suggesting the
      independent phylogenetic evolution of the mitochondrial dsRNA. Consensus sequence
      for RNA-dependent RNA polymerase was found within the longer ORF (2472 bp) of the
      dsRNA. The overlapping 52 bp of the ORFs in different reading frames is
      suggestive of the occurrence of a -1 ribosomal frameshift in the mitochondrial
      translation system. The observed simple genetic structures suggest that the algal
      mitochondrial dsRNA might be deficient in a gene for movement from cell to cell
      in host plants and, hence, has a plasmid-like nature that is distinct from that
      of infectious plant viruses. The nature and origin of the endogenous dsRNAs of
      various sizes and their relationships are discussed.

PMID- 9526506
TI  - Induction of AGAMOUS gene expression plays a key role in ripening of tomato
      sepals in vitro.
AB  - In vitro culture of VFNT Cherry tomato sepals (calyx) at 16-21 degrees C results
      in developmental changes that are similar to those that occur in fruit tissue
      [10]. Sepals become swollen, red, and succulent, produce ethylene, and have
      increased levels of polygalacturonase RNA. They also produce many flavor
      volatiles characteristic of ripe tomato fruit and undergo similar changes in
      sugar content [11]. We examined the expression of the tomato AGAMOUS gene, TAG1,
      in ripening, in vitro sepal cultures and other tissues from the plant and found
      that TAG1 RNA accumulates to higher levels than expected from data from other
      plants. Contrary to reports on the absence of AGAMOUS in sepals, TAG1 RNA levels
      in green sepals from greenhouse-grown plants is detectable, its concentration
      increasing with in vitro ripening to levels that were even higher than in red,
      ripe fruit. Sepals of fruit on transgenic tomato plants that expressed TAG1
      ectopically were induced by low temperature to ripen in vivo, producing lycopene
      and undergoing cell wall softening as is characteristic of pericarpic tissue. We
      therefore propose that the induction of elevated TAG1 gene expression plays a key
      role in developmental changes that result in sepal ripening.

PMID- 9526507
TI  - Identification of UV/blue light-response elements in the Arabidopsis thaliana
      chalcone synthase promoter using a homologous protoplast transient expression
      system.
AB  - To identify DNA sequences of the Arabidopsis thaliana chalcone synthase gene
      (CHS) concerned with induction by UV-B and UV-A/blue light, AtCHS promoter
      constructions were assayed by transient expression in protoplasts prepared from
      two different lines of cultured A. thaliana cells. The protoplasts responded
      similarly to A. thaliana leaf tissue in light-dependent CHS transcript
      accumulation. The reporter enzyme beta-glucuronidase (GUS) was used to monitor
      light-responsive promoter activity. A 1972 bp promoter conferred UV-B and UV
      A/blue light induction of GUS activity. Deletion to 164 bp resulted in reduced
      promoter strength but retention of responsiveness to UV-B and UV-A/blue light.
      Further deletion abolished transcriptional activity. The 164 bp promoter contains
      sequences closely resembling LRUPcCHS, (light-responsive unit of the Petroselinum
      crispum CHS promoter). This A. thaliana CHS promoter region, designated LRUAtCHS,
      was sufficient to confer UV-B and UV-A/blue light responsiveness to a
      heterologous core promoter. Mutation of sequences in LRUAtCHS corresponding to
      the ACGT element and the MYB recognition element of LRUPcCHS resulted in
      inactivation of the 164 bp and 335 bp promoter deletions. However, the mutant 668
      bp promoter retained residual UV-B and UV-A/blue light-induced expression,
      indicating the presence of additional functional sequences upstream of -335.
      Mutation of a single G-box-like sequence around -442 had no effect on light
      responsiveness, indicating that it does not function in light regulation of this
      promoter. Since no difference in responsiveness to UV-B and UV-A/blue light was
      observed with any promoter variant, we conclude that the two phototransduction
      pathways regulate transcription factors which interact with common promoter
      elements. The results from-our analysis of a A. thaliana light-responsive
      promoter will facilitate the study of light-dependent gene regulation by genetic
      means in Arabidopsis thaliana.

PMID- 9526509
TI  - Molecular evolution of cdc2 pseudogenes in spruce (Picea).
AB  - The p34cdc2 protein and other cyclin-dependent protein kinases (CDK) are
      important regulators of eukaryotic cell cycle progression. We have previously
      cloned a functional cdc2 gene from Picea abies and found it to be part of a
      family of related sequences, largely consisting of pseudogenes. We now report on
      the isolation of partial cdc2 pseudogenes from Picea engelmannii and Picea
      sitchensis, as well as partial functional cdc2 sequences from P. engelmannii, P.
      sitchensis and Pinus contorta. A high level of conservation between species was
      detected for these sequences. Phylogenetic analyses of pseudogene and functional
      cdc2 sequences, as well as the presence of shared insertions or deletions,
      support the division of most of the cdc2 pseudogenes into two subfamilies. New
      cdc2 pseudogenes appear to have been formed in Picea at a much higher rate than
      they have been obliterated by neutral mutations. The pattern of nucleotide
      changes in the cdc2 pseudogenes, as compared to a presumed ancestral functional
      cdc2 gene, was similar to that previously found in mammalian pseudogenes, with a
      strong bias for the transitions C to T and G to A, and the transversions C to A
      and G to T.

PMID- 9526510
TI  - MtENOD16 and 20 are members of a family of phytocyanin-related early nodulins.
AB  - We have identified two single-copy genes from the model legume. Medicago
      truncatula (MtENOD16 and 20) whose expression can be correlated with early stages
      of root nodulation and whose predicted coding sequences are partially homologous
      to both pea/vetch ENOD5 and soybean N315/ENOD55. Database searching and sequence
      alignment have defined the encoded early nodulins as a distinct sub-family of
      phytocyanin-related proteins, although the absence of key ligands implies that
      they are unlikely to bind copper. Molecular modelling based on known phytocyanin
      structure has been used to predict the 3-dimensional conformation of the
      principle globular domain of MtENOD16/20. Additional structural features common
      to both early nodulin and phytocyanin precursors include an N-terminal transit
      peptide, a highly variable (hydroxy)proline-rich sequence which probably
      undergoes extensive post-translational modification, and a hydrophobic C-terminal
      tail.

PMID- 9526511
TI  - The capsanthin-capsorubin synthase gene: a candidate gene for the y locus
      controlling the red fruit colour in pepper.
AB  - The red colour of pepper fruits is determined by the y+ dominant allele and the
      yellow colour by the y recessive allele. The capsanthin-capsorubin synthase (CCS)
      gene is activated specifically during the final stages of pepper fruit ripening.
      RFLP and specific-PCR polymorphisms derived from the CCS gene were analysed in a
      F2 progeny of a red by yellow-fruited cross. They cosegregated completely with
      fruit colour. Our results support the hypothesis that the yellow phenotype might
      result from a deletion of the CCS gene. These specific markers were integrated
      into the genetic map and will be useful for marker assisted plant breeding.

PMID- 9526508
TI  - A novel aromatic alcohol dehydrogenase in higher plants: molecular cloning and
      expression.
AB  - Cinnamyl alcohol dehydrogenase (CAD; EC 1.1.195) catalyses the conversion of p
      hydroxy-cinnamaldehydes to the corresponding alcohols and is considered a key
      enzyme in lignin biosynthesis. In a previous study, an atypical form of CAD (CAD
      1) was identified in Eucalyptus gunnii [12]. We report here the molecular cloning
      and characterization of the corresponding cDNA, CAD 1-5, which encodes this novel
      aromatic alcohol dehydrogenase. The identity of CAD 1-5 was unambiguously
      confirmed by sequence comparison of the cDNA with peptide sequences derived from
      purified CAD 1 protein and by functional expression of CAD 1 recombinant protein
      in Escherichia coli. Both native and recombinant CAD 1 exhibit high affinity
      towards lignin precursors including 4-coumaraldehyde and coniferaldehyde, but
      they do not accept sinapaldehyde. Moreover, recombinant CAD 1 can also utilize a
      wide range of aromatic substrates including unsubstituted and substituted
      benzaldehydes. The open reading frame of CAD 1-5 encodes a protein with a
      calculated molecular mass of 35,790 Da and an isoelectric point of 8.1. Although
      sequence comparisons with proteins in databases revealed significant similarities
      with dihydroflavonol-4-reductases (DFR; EC 1.1.1.219) from a wide range of plant
      species, the most striking similarity was found with cinnamoyl-CoA reductase
      (CCR; EC 1.2.1.44), the enzyme which directly precedes CAD in the lignin
      biosynthetic pathway. RNA blot analysis and immunolocalization experiments
      indicated that CAD 1 is expressed in both lignified and unlignified
      tissues/cells. Based on the catalytic activity of CAD 1 in vitro and its
      localization in planta, CAD 1 may function as an 'alternative' enzyme in the
      lignin biosynthetic pathway. However, additional roles in phenolic metabolism are
      not excluded.

PMID- 9526512
TI  - Molecular characterization of a cytokinin-inducible periwinkle protein showing
      sequence homology with pathogenesis-related proteins and the Bet v 1 allergen
      family.
AB  - Cytokinin treatment of periwinkle callus cultures increased the accumulation of a
      protein, designated T1, in two-dimensional separated protein extracts. The first
      30 NH2-terminal amino acids were determined by Edman degradation and showed
      significant sequence homology with intracellular pathogenesis-related (IPR) plant
      proteins and the Bet v 1 allergen family. The deduced amino acid sequence of
      cDNAs coding for T1, isolated by RT-PCR and 5' RACE-PCR, exhibited an average
      sequence identity of 40% with both IPR and Bet v 1-related allergens. T1 and all
      related proteins contained a p-loop motif typically found in nucleotide-binding
      proteins as the most conserved sequence feature. Northern blot analysis showed
      that cytokinin treatment of periwinkle callus induced T1 transcripts, whereas
      addition of 2,4-dichlorophenoxyacetic acid inhibited this accumulation.
      Hybridization of genomic periwinkle DNA with the T1 cDNA suggested that the
      protein is encoded by a single-copy gene. Immunoblot studies with a panel of Bet
      v 1-specific antibodies and sera from Bet v 1 allergic individuals identified T1
      as a protein that is immunologically distinct from the Bet v 1 allergen family
      and has no allergenic properties.

PMID- 9526515
TI  - Anatomic resection for severe liver trauma.
AB  - BACKGROUND: Most publications during the past decade have condemned the use of
      anatomic resection for liver trauma and advocated a conservative surgical
      approach when operative intervention was required. This policy has been supported
      by the high mortality rate reported by most authorities. The purpose of this
      study was to assess the results of anatomic hepatic resection for liver trauma in
      an institution in which the hepatobiliary surgeons are responsible for the
      management of severe liver injuries. METHODS: During the period 1983 to 1996, 287
      patients with liver injuries were admitted to the hospital and 37 patients with
      severe liver trauma underwent anatomic resection. Demographic, clinical,
      operative, and postoperative data were collected and analyzed. The resections
      performed included right hemihepatectomy (n = 27), left hemihepatectomy (n = 1),
      left lateral segment resection (n = 5), and segmental resection (n = 4). RESULTS:
      There were three postoperative deaths after right hemihepatectomy (11.1%) and an
      overall mortality rate of 8.1%. There were no intraoperative deaths.
      Postoperative complications occurred in 22 patients (60%) and were most frequent
      in patients with concomitant injuries to other systems. Liver-related morbidity
      occurred in seven patients (19%). The median postoperative stay was 20 days.
      CONCLUSIONS: Anatomic hepatic resection for trauma is associated with low
      mortality and liver-related morbidity rates when performed by experienced
      hepatobiliary surgeons, and its role in the management of severe hepatic trauma
      should be reevaluated.

PMID- 9526513
TI  - Root-specific expression of a Zea mays gene encoding a novel glycine-rich
      protein, zmGRP3.
AB  - The isolation and characterization of a cDNA clone from Zea mays coding for a
      novel glycine-rich protein (GRP) is described. The corresponding 1.4 kb mRNA
      accumulates exclusively in roots (primary, lateral seminal and crown roots) of
      young maize seedlings, following developmentally specific patterns. In agreement
      with previously described GRPs from other plant species the derived protein
      sequence exhibits a hydrophobic domain at the N-terminal region followed by
      repeated glycine-rich motifs. Genomic Southern analysis indicates that the zmGRP3
      gene is present in the maize genome as one or two copies or at a low copy number.

PMID- 9526514
TI  - A putative rolB gene homologue of the Agrobacterium rhizogenes TR-DNA has
      different morphogenetic activity in tobacco than rolB.
AB  - Agrobacterium rhizogenes strains of the agropine type harbor on their Ri-plasmid
      two T-DNAs, a left TL-DNA and a right TR-DNA. The rolB gene of the TL-DNA is the
      major factor in the pathogenesis of the hairy-root disease and its constitutive
      expression interfere profoundly with plant morphogenesis. We have tested whether
      the expression of its sequence related putative homologue from the TR-DNA
      (rolBTR) may cause also bacterial virulence or affect plant development. Unlike
      rolB, rolBTR is unable to induce root formation on tobacco leaf discs. Tobacco
      plants expressing a chimeric 35S::rolBTR gene have reduced stature, off-shoots at
      the stem base and bent and wrinkled leaves with epinastic growth. 14 N-terminal
      amino acids which are absent in the rolB protein are indispensable to rolBTR
      protein activity. The characteristic tyrosine phosphatase super family motif CX5R
      is absent in the rolBTR protein. For rolB this motif is possibly functionally
      relevant. We conclude that the rolBTR gene product has morphogenic activity but
      is not a functional homologue of the rolB protein.

PMID- 9526516
TI  - The inflammatory effects of crystalline cholesterol monohydrate in the guinea pig
      gallbladder in vivo.
AB  - BACKGROUND: The etiologic role of crystalline material in inflammatory arthritis
      is well established. The role of crystals in cholecystitis is unclear. We
      hypothesized that crystalline cholesterol monohydrate stimulates guinea pig
      gallbladder inflammation in vivo. METHODS: Crystalline cholesterol monohydrate,
      lipopolysaccharide (LPS), lysolecithin, polystyrene latex spheres
      (noninflammatory particles), and saline were instilled into guinea pig
      gallbladders for 24 to 72 hours after cystic duct ligation. Water transport
      across gallbladder mucosa was measured. Gallbladder tissue was analyzed for mucus
      layer thickness, myeloperoxidase, prostaglandin E2 (PGE2) prostaglandin F-1 alpha
      (PGF-1 alpha), and interleukin-1. Luminal fluid was also examined for PGE2 and
      PGF-1 alpha. Values for each test were compared with saline controls by using
      Student's test (p < 0.05). RESULTS: Crystalline cholesterol, LPS, and
      lysolecithin caused significant reduction in mucus layer thickness, reversed
      water absorption to secretion across the gallbladder mucosa, caused significant
      increases in myeloperoxidase and interleukin-1 in gallbladder tissue, and caused
      significant increases in PGE2 and PGF-1 alpha in luminal fluid. These effects
      were generally dose- but not time-dependent. Polystyrene latex particles caused
      no difference in outcomes compared with saline controls. CONCLUSIONS: Crystalline
      cholesterol monohydrate has dose-dependent inflammatory effects in the guinea pig
      gallbladder in vivo that are not simply-due to mechanical irritation of the
      gallbladder wall by crystalline particles. Crystals in the gallbladder may have
      an etiologic role in cholecystitis.

PMID- 9526517
TI  - Preoperative staging of colorectal cancer by a 15 MHz ultrasound miniprobe.
AB  - BACKGROUND: Our objective was to examine the accuracy of a 15 MHz ultrasound
      miniprobe in the pre-operative staging of colorectal cancer by assessing the
      depth of tumor infiltration and involvement of pericolonic lymph nodes. METHODS:
      Thirty-three patients with colorectal cancer who underwent ultrasonography with a
      miniprobe were studied prospectively. The results of this imaging were compared
      with the histologic findings of the resected specimens. RESULTS: The accuracy of
      the miniprobe for depth of invasion (T category) was 82% (27 of 33) for all
      tumors, 76% (13 of 17) in pT1 cases, and 88% (14 of 16) in pT2 to pT4 cases. The
      accuracy of the miniprobe for nodal staging (N category) was 87% (26 of 30)
      overall. The sensitivity was 63% (5 of 8), the specificity was 95% (21 of 22),
      the positive predictive value was 83% (5 of 6), and the negative predictive value
      was 88% (21 of 24). CONCLUSIONS: The miniprobe is an accurate method for the
      preoperative TN staging of colorectal cancer. We recommend its preoperative use
      because the results may influence the surgical approach.

PMID- 9526518
TI  - Hepatic resection for bilobar multicentric hepatocellular carcinoma: is it
      justified?
AB  - BACKGROUND: Hepatic resection for multiple hepatocellular carcinomas (HCCs)
      involving both lobes of the liver is rarely recommended because of high operative
      risks and low radicality. Thus the justification of hepatic resection for bilobar
      multicentric HCC remains undefined. METHODS: Two hundred eleven patients with
      HCC, who underwent curative hepatic resection, were studied retrospectively. The
      patients were divided into two groups. Group A consisted of 39 patients with
      bilobar (both sides of Cantlie's line) multicentric HCCs. Group B consisted of
      172 patients with HCC with solitary or unilobar lesions. The backgrounds and
      resectional results of patients in groups A and B were compared. RESULTS:
      Patients in group A usually required multiple separate liver resections and a
      longer operative time. However, the operative blood loss, amount of blood
      transfused, and operative morbidity and mortality rates were not significantly
      different. Patients in group A showed higher incidences of associated satellite
      nodules, microscopic vascular invasion, and a lack of capsules. The 6-year
      disease-free and actuarial survival rates of patients in groups A and B were
      30.5% and 41.8% (p = 0.17) and 42.9% and 51.4% (p = 0.12), respectively. For
      patients in group A the presence of satellite nodules in any resected tumor was
      the only independent unfavorable feature that influenced the actuarial survival
      rate after multivariate analysis. CONCLUSIONS: Liver resection is justified for
      bilobar multicentric HCCs in selected patients, if the tumors can be totally
      resected. Postoperative adjuvant therapies should be considered when satellite
      nodules are present in any resected tumor.

PMID- 9526519
TI  - Response of patients with cirrhosis who have undergone partial hepatectomy to
      treatment aimed at achieving supranormal oxygen delivery and consumption.
AB  - BACKGROUND: This study was undertaken to evaluate the response to therapy aimed
      at achieving supranormal cardiac and oxygen transport variables (cardiac index >
      than 4.5 L/min/m2, oxygen delivery > 600 ml/min/m2, and oxygen consumption > 170
      ml/min/m2) in patients with cirrhosis who have undergone partial hepatectomy and
      to assess the relationship between those parameters and outcome. METHODS: Thirty
      four consecutive patients underwent elective hepatectomy for hepatocellular
      carcinoma. The postoperative outcomes and hemodynamic and oxygen transport values
      in 16 patients (group S) who maintained supranormal values were compared with
      those in 18 patients (group N) treated to maintain normal hemodynamic values.
      Patients in group S received volume expansion and then, if necessary, dobutamine
      (3 to 15 micrograms/kg/min) to increase cardiac index, oxygen delivery, and
      oxygen comsumption simultaneously during the first 12 hours. RESULTS: The
      hemodynamic targets were reached by 56% of patients in group S during the first
      12 hours and 31% during the next 12 hours. Postoperative blood lactate levels at
      12 and 24 hours were lower in group S than in group N, and total bilirubin
      concentrations, hepatic venous oxygen saturation, and arterial ketone body ratio,
      useful markers of postoperative liver function, also showed more favorable
      changes in group S than in group N. Postoperative morbidity and mortality rates
      were not significantly different in the two groups, but the incidence of
      hyperbilirubinemia and liver failure was much lower in group S than in group N.
      CONCLUSIONS: These results suggest that fluid therapy aimed at achieving a
      supranormal pattern by 12 hours after hepatectomy improved the systemic oxygen
      demand-supply dynamics and hepatic hemodynamics, decreasing the incidence of
      postoperative hyperbilirubinemia and liver failure in patients with liver
      cirrhosis.

PMID- 9526520
TI  - Diphenylhydantoin sodium promotes early and marked angiogenesis and results in
      increased collagen deposition and tensile strength in healing wounds.
AB  - BACKGROUND: Sodium diphenylhydantoin (DpH) (phenytoin) was first introduced as an
      antiepileptic in 1938. One of its side effects, gingival hyperplasia, prompted
      investigation into the possible application of this drug as a promoter of wound
      healing. Since the late 1950s phenytoin has been used in a variety of clinical
      situations. However, its exact mechanism of action is still debated. The aim of
      this study was to determine the effect of DpH on wound healing in an incisional
      rat model. METHODS: A four dorsal wound model was used, and each cephalad wound
      had a polyvinyl alcohol sponge placed in a subcutaneous pocket just above its
      cephalad end. Caudal and cephalad wounds were treated with 10 mg DpH in 200
      microliters carrier, and the other two wounds received an equal volume of the
      saline vehicle as controls on the day of wounding and on the third and sixth
      postoperative days. The animals were killed on the tenth postwounding day.
      Tensile strength of fresh and fixed scars was determined using constant speed
      tensiometry, and wound hydroxyproline was determined spectophotometrically.
      RESULTS: There was a highly significant increase in both fresh and fixed wound
      tensile strength of all DpH-treated wounds compared with controls (p < 0.001).
      This was reflected by a significant increase in polyvinyl alcohol sponge
      hydroxyproline in DpH-treated wounds compared with saline-treated wounds (p =
      0.002). Histologic examination of these wounds was performed at 3 and 6 days
      after wounding. There was moderate fibroblast infiltration with a marked
      inflammatory infiltrate and neovascularization in the DpH-treated wounds compared
      with controls at 3 days. By day 6, the inflammatory infiltrate had almost totally
      receded in the treated wounds, but fibroblast infiltration and angiogenesis were
      still persistently marked. In comparison, the saline-treated wounds still had
      moderate inflammatory and fibroblast infiltrate and mild angiogenesis.
      CONCLUSIONS: DpH alters the natural course of wound healing and may be of benefit
      in clinical situations where defective wound collagen deposition may lead to poor
      wound healing and consequent morbidity and mortality.

PMID- 9526521
TI  - Age-related differences in response to neutrophil-mediated reperfusion injury in
      the neonatal piglet heart.
AB  - BACKGROUND: Neonatal hearts have altered adhesion molecule interactions in
      response to ischemia-reperfusion. How this affects myocardial function is
      unknown. METHODS: Isolated, buffer perfused 0- to 2-day (newborn) and 2-week
      piglet hearts were first subjected to 20-minute global, normothermic ischemia,
      followed by 45 minutes of reperfusion during which 150 x 10(6) newborn or 2-week
      neutrophils were infused. In some hearts, an antibody to SLe(x) (CSLEX-1) was
      infused with neutrophils during reperfusion. Hemodynamic variables, including
      left ventricular developed pressure (LVDP), were recorded at timed intervals.
      Neutrophil CD-18, L-selectin, and SLe(x) contents were measured by flow
      cytometry. RESULTS: Full recovery of LVDP was observed in newborn hearts
      receiving newborn or 2-week-old neutrophils. Recovery of LVDP was depressed (p <
      0.01, ANOVA) in 2-week-old hearts receiving 2-week old, not newborn, neutrophils.
      Infusion of CSLEX-1 in 2-week-old hearts restored LVDP to baseline. Whereas flow
      cytometry showed higher (p < 0.01, Student's t test) CD-18 and L-selectin
      expression on newborn versus 2-week-old neutrophils, newborn neutrophils
      expressed lower (p < 0.01) SLe(x) levels. CONCLUSIONS: Initial "loose" neutrophil
      endothelial selectin interactions are a necessary prelude to "firm" adhesion and
      reperfusion injury. Operations performed soon after birth may be better tolerated
      than when surgery is delayed; anti-SLe(x) preparations may prove beneficial when
      performing cardiac procedures on older infants.

PMID- 9526523
TI  - Is laparoscopic cholecystectomy hazardous for gallbladder cancer?
AB  - BACKGROUND: There have been several case reports of unexpected gallbladder cancer
      diagnosed after laparoscopic cholecystectomy (LC) being associated with fatal
      recurrence of cancer in the abdominal wall. Therefore there is a risk that LC
      might worsen the prognosis of gallbladder cancer. The objective of this study was
      to examine the frequency of recurrence of cancer in the abdominal wall and the
      prognosis of patients with unexpected gallbladder cancer diagnosed after LC.
      METHODS: A clinicopathologic study was performed on 30 patients with
      postoperatively diagnosed gall-bladder cancer among 3566 patients undergoing LC
      at 19 institutions. The cumulative survival rate was compared with that reported
      for gallbladder cancer diagnosed after open cholecystectomy. RESULTS: Recurrence
      of cancer in the abdominal wall occurred in three patients, and two of them died.
      The 3-year survival rate was 100% for early gallbladder cancer and 70% for
      advanced tumors. These results were comparable to the 3-year survival rates for
      gallbladder cancer diagnosed after open cholecystectomy. CONCLUSIONS: The
      incidence of recurrence of cancer in the abdominal wall was increased, but the
      medium-term prognosis was not worsened by laparoscopy. It does not appear
      necessary to exclude patients with cholecystitis or gallbladder wall hypertrophy
      from undergoing laparoscopic procedures on the grounds that they might have
      gallbladder cancer.

PMID- 9526522
TI  - Congenital diaphragmatic hernia survival and use of extracorporeal life support
      at selected level III nurseries with multimodality support.
AB  - BACKGROUND: Congenital diaphragmatic hernia (CDH) has been cited to have a
      mortality rate of 50%. There have been multiple studies at individual
      institutions demonstrating potential benefits from various strategies including
      extracorporeal life support (ECLS), delayed repair, and lower levels of
      ventilator support. There has been no multicenter survey of institutions offering
      these modalities to describe the current use of ECLS and survival of these
      infants. In addition, the relationship between the number of patients with CDH
      managed at an individual institution and outcome has not been evaluated. METHODS:
      We queried 16 level III neonatal intensive care centers on the use of ECLS and
      survival of infants with CDH who were treated during 2 consecutive years (1993 to
      1995). Data are presented as mean +/- SEM, median, and range. RESULTS: Data were
      collected on 411 patients. Of these, 71% +/- 8% were outborn and 8% +/- 3% were
      considered nonviable. Overall survival of CDH infants was 69% +/- 4% (range, 39%
      to 95%). The survival rate of infants on ECLS was 55% +/- 4%, whereas survival of
      infants not requiring ECLS was significantly increased at 81% +/- 5% (p = 0.005).
      The mean rate of ECLS use was 46% +/- 2%. There was no correlation between the
      number of cases per year at an individual institution and overall survival, ECLS
      survival, or ECLS use (r = 0.341, 0.305, and 0.287, respectively). There was also
      no correlation between case volume at an individual institution and ECLS survival
      (r = 0.271). CONCLUSIONS: The current survival rate and rate of ECLS use in
      infants with CDH at level III neonatal intensive care units in the United States
      are 69% +/- 4% and 46% +/- 2%, respectively. There is no correlation between the
      yearly individual center experience with managing CDH and rate of ECLS use or
      outcome.

PMID- 9526524
TI  - Variable effect of streptozotocin-diabetes on the growth of hamster pancreatic
      cancer (H2T) in the Syrian hamster and nude mouse.
AB  - BACKGROUND: Streptozotocin-diabetes prevents induction of pancreatic tumors in
      several animal models and inhibits the growth of established human pancreatic
      cancer implants in nude mice. However, it also promotes growth of the hamster
      pancreatic cancer cell line, H2T, in the Syrian hamster. To test the hypothesis
      that these contradictory effects are due to tumor host differences, the growth of
      the H2T cell line was examined in the streptozotocin-diabetic nude mouse.
      METHODS: H2T cells were implanted subcutaneously into streptozotocin-diabetic
      nude mice (n = 10) and untreated control mice (n = 10). After 21 days, tumors
      were excised and weighed. Plasma insulin and somatostatin were determined by
      radioimmunoassay. RESULTS: After 3 weeks, tumors in the control group weighed 118
      mg and tumors in the diabetic group weighed 28 mg (p < 0.001). Plasma insulin was
      significantly decreased in the streptozotocin-treated animals compared with
      control animals (insulin, 23 microU/ml vs 31 microU/ml; p < 0.001). In contrast,
      somatostatin was significantly elevated in the streptozotocin-diabetic group
      compared with the control group (somatostatin, 179 pg/ml versus 54 pg/ml, p <
      0.001). Competitive binding studies revealed specific cell surface receptors for
      insulin (Kd, 15.5 nmol/L), and somatostatin (Kd, 2.5 nmol/L) on the H2T cells. In
      an in vitro cell proliferation assay, cell division was promoted by insulin (p <
      0.01, maximum +11%) and inhibited by somatostatin (p < 0.01, maximum -18%).
      CONCLUSIONS: The variable effect of streptozotocin-diabetes on pancreatic cancer
      growth is due to differences in the tumor host. The growth of pancreatic cancer,
      particularly in streptozotocin-diabetic nude mice, may be influenced by gut
      peptides in a receptor-dependent fashion.

PMID- 9526525
TI  - Extrinsic innervation modulates canine jejunal transport of glutamine, alanine,
      leucine, and glucose.
AB  - BACKGROUND: We previously showed a decrease in ileal glutamine transport in vitro
      and net absorption in vivo after extrinsic denervation of the canine jejunoileum.
      The aim was to determine whether extrinsic innervation modulates in vivo net
      absorption and in vitro transport of glutamine and other nutrients in canine
      jejunum. METHODS: In vivo net jejunal uptakes of glutamine, alanine, leucine, and
      glucose were measured in five dogs before and 2 and 8 weeks after a model
      neurally isolating in situ the jejunoileum (extrinsic denervation, intestinal
      transection). To assess mechanisms, carrier-mediated uptakes were quantitated in
      jejunal brush border membrane vesicles from six dogs before and at 2 and 8 weeks
      after neural isolation of the jejunoileum and compared with six control dogs with
      fully intact extrinsic innervation. RESULTS: In vivo net absorption of glutamine
      decreased at 2 weeks (p < 0.05) and returned to normal values at 8 weeks; net
      absorptions of leucine, alanine, and glucose were decreased at both 2 and 8
      weeks. In vitro brush border membrane vesicles transport of glutamine, leucine,
      and alanine followed the patterns of in vivo absorption, but glucose transport
      did not differ at any time point. Decreased glutamine uptake at 2 weeks resulted
      from a decrease in Vmax rather than a change in K(m) in sodium-dependent carrier
      mediated transport. CONCLUSIONS: Extrinsic denervation down-regulated carrier
      mediated transport of amino acids but not glucose. Decreased in vitro glutamine
      transport was mediated in part by a decrease in number rather than affinity of
      sodium-dependent transporters.

PMID- 9526526
TI  - Gastric carcinoma with pyloric stenosis.
AB  - BACKGROUND: The surgical outcome of gastric carcinomas with pyloric stenosis and
      their prognostic factors are sparsely documented. METHODS: A clinicopathologic
      study of gastric carcinoma with pyloric stenosis (PS group, n = 122) was done and
      findings were compared with the cases involving the antrum (A group, n = 695).
      Independent prognostic factors for survival of the patients with PS were
      determined by Cox's proportional hazard model. RESULTS: There were no differences
      in age and gender between the two groups. The PS group was characterized by an
      infiltrating growth pattern and undifferentiated adenocarcinoma. The incidence of
      serosal invasion, direct invasion into neighboring organs, peritoneal
      dissemination, lymph node metastasis, and liver metastasis of the PS group was
      higher than those of the A group (p < 0.01). The resection rate and 5-year
      survival of the PS group were 78% and 22%, respectively; these values were
      significantly lower than 98% and 58% of the A group (p < 0.01). Multivariate
      analyses showed that operative curability, resection of the stomach, liver
      metastasis, serosal invasion, and histologic type were the independent prognostic
      factors of the PS group. CONCLUSIONS: In cases of gastric carcinoma with pyloric
      stenosis, efforts should be made to do a curative operation, but for other
      patients with poor prognostic factors, intensive surgery and adjuvant therapy
      should be considered.

PMID- 9526527
TI  - Safety and efficacy of isolated perfusion of extremities for recurrent tumor in
      elderly patients.
AB  - BACKGROUND: The treatment of bulky recurrent melanotic lesions of extremities
      with isolated limb perfusion with high dose chemotherapy offers palliation in a
      number of patients. However, the question is raised whether these major surgical
      procedures are too risky to warrant performing them in elderly patients. METHODS:
      Sixty-seven limbs were perfused in 60 patients with various drugs from 1976
      through 1996 (35, imidazole carboxamide; 7, cisplatin; 20, carboplatin; 5,
      thiotepa). Among the 67 perfusions, 20 were in patients aged 70 years and older.
      Perfusion was performed for 16 upper extremities and 51 lower extremities by
      using the pump oxygenator for 1 hour. RESULTS: A total of 19 complications were
      noted after a total of 14 of the 67 perfusions (21%) (postoperative edema, 5;
      seroma, 4; wound separation or infection, 9; nonfatal pulmonary embolus, 1). The
      complications in 4 of 20 perfusions in the older patients (20%) were less than in
      15 of 47 perfusions in the younger patients (32%). Among the 17 patients older
      than 70 years of age who were treated with perfusions for recurrent disease, four
      patients (24%) are alive with no evidence of disease (NED) for a median of 29
      months (range, 16 to 80 months); one patient is now more than 6 years with NED
      after her third perfusion for repeated in-transit disease. Another 2 of 17
      patients (12%) are alive with disease for a median of 89 months (range, 54 to 123
      mos). The remaining 11 patients (64%) are dead of their disease. These data are
      comparable to the control rates in the group of younger patients in the study.
      Overall, half of all the patients (14 of 28) who died of their disease in both
      groups had maintained local control of their involved extremities. CONCLUSIONS:
      Aggressive treatment in selected patients with regional isolated perfusion of
      limbs for melanoma can lead to significant palliation of symptoms and salvage of
      limbs with adequate disease-free control and occasional survival benefit. This
      series of patients was associated with meaningful disease control and with few
      serious complications. Perfusions are tolerated well by patients in their 70s and
      80s; therefore advanced age is not a contraindication to this procedure in
      carefully selected patients.

PMID- 9526528
TI  - The acutely ischemic extremity after kidney transplant: an approach to
      management.
AB  - BACKGROUND: The purpose of this study was to review arterial thromboembolic
      complications presenting with an acutely ischemic lower extremity after a kidney
      (KTx) or simultaneous kidney-pancreas transplantation (SPK) and to describe an
      approach to their management. METHODS: We retrospectively reviewed all such
      transplantations (a total of 2109) performed between January 1985 and August
      1995. We identified 16 recipients (incidence, 0.76%) in whom an acutely ischemic
      leg developed during the immediate postoperative period (within the first 48
      hours). RESULTS: Of the 16 recipients, eight underwent a KTx (incidence, 0.45%)
      and eight underwent an SPK transplantation (incidence, 2.90%). Median age was 38
      years (range, 15 months to 61 years). Thirteen had insulin-dependent diabetes
      mellitus (IDDM), a significantly higher incidence than in the control group
      (i.e., transplant recipients without this complication) (p < 0.01). Peripheral
      vascular disease (PVD) was documented before operation in eight (50%) of the
      recipients (vs 8.9% in the control group) (p < 0.01). Ten were uremic (on chronic
      dialysis) before transplantation; six were nonuremic (not on dialysis).
      Intraoperatively, 14 had moderate to severe atherosclerotic disease affecting the
      iliac vessels, seven of whom required some manipulation of the artery (either
      endarterectomy or tacking of the intima) to make it suitable for anastomosis.
      Heparin was administered systemically during cross clamping to only four. Most of
      the 16 recipients showed symptoms or signs of arterial occlusion within the first
      few hours after operation. The most common symptom was pain; the most common
      physical finding was loss of femoral and distal pulses. Thirteen recipients had
      moderate to severe ischemia, as judged by physical examination; 15 returned to
      the operating room for surgical exploration. Eight underwent thrombectomy through
      an inguinal incision, with successful restoration of flow. Seven underwent
      exploration through the initial incision because of concern regarding the
      viability of the transplanted organ; five of them required transplant nephrectomy
      because of simultaneous thrombosis of the renal artery. No patient needed a
      bypass procedure to restore flow. Long-term morbidity as a result of the arterial
      occlusion was related to the severity and length of ischemia. CONCLUSIONS: On the
      basis of these results, we suggest the following recommendations: (1) all
      patients should undergo a thorough peripheral vascular examination before and
      after transplantation; (2) patients at higher risk for arterial thromboembolic
      complications (e.g., those with significantly diseased vessel at intraoperative
      examination, nonuremic patients) should receive intraoperative systemic heparin
      before cross clamping of the artery; and (3) patients with signs or symptoms
      suggesting arterial occlusion after operation should undergo prompt surgical
      exploration.

PMID- 9526529
TI  - Repair of type III and type IV thoracoabdominal aortic aneurysms by using a long
      beveled anastomosis: a description of technique.

PMID- 9526530
TI  - Adult-onset dermatomyositis with severe gastrointestinal manifestations: case
      report and review of the literature.

PMID- 9526531
TI  - External jugular varix with an intravascular hemangioendothelioma.

PMID- 9526532
TI  - The gargantuan marginal artery sign: a case report of averting total necrosis of
      the small intestine.

PMID- 9526533
TI  - Repair of reconstructed gastric tube bronchial fistulas after operation for
      esophageal cancer by transposing a pedicled pectoralis major muscle flap: report
      of three successful cases.

PMID- 9526534
TI  - A novel therapeutic strategy for the management of idiopathic chylopericardium
      and chylothorax.

PMID- 9526536
TI  - Coat protein gene sequences of garlic and onion isolates of the onion yellow
      dwarf potyvirus (OYDV).
AB  - Partial genomic sequences from an unknown garlic potyvirus and from an onion
      isolate of the onion yellow dwarf potyvirus (OYDV) were obtained. Comparison of
      the deduced amino acid sequences showed a similarity of 88% between the
      respective viral coat proteins. The garlic potyvirus coat protein was expressed
      in E. coli cells, purified, and subjected to Western blot analysis using
      antibodies raised against different garlic-infecting viruses. The expression
      protein was consistently recognised by anti-OYDV antibodies and did not react
      with antibodies specific for leek yellow stripe potyvirus (LYSV), garlic common
      latent carlavirus (GCLV) and shallot latent carlavirus (SLV). Besides, the garlic
      potyvirus coat protein was obtained as a fusion protein and used as antigen to
      produce polyclonal antibodies. These antibodies reacted with purified OYDV
      virions, but failed to recognise LYSV particles. In the light of this evidence
      the garlic potyvirus was identified as the garlic strain of OYDV.

PMID- 9526535
TI  - RNA-mediated virus resistance in transgenic plants.
AB  - In recent years the concept of pathogen-derived resistance (PDR) has been
      successfully exploited for conferring resistance against viruses in many crop
      plants. Starting with coat protein-mediated resistance, the range has been
      broadened to the use of other viral genes as a source of PDR. However, in the
      course of the efforts, often no clear correlation could be made between
      expression levels of the transgenes and observed virus resistance levels. Several
      reports mentioned high resistance levels using genes incapable of producing
      protein, but in these cases, even plants accumulating high amounts of transgene
      RNA were not most resistant. To accommodate these unexplained observations, a
      resistance mechanism involving specific breakdown of viral RNAs has been
      proposed. Recent progress towards understanding the RNA-mediated resistance
      mechanism and similarities with the co-suppression phenomenon will be discussed.

PMID- 9526537
TI  - Sequence diversity in the NIb coding region of eight sugarcane mosaic potyvirus
      isolates infecting sugarcane in Australia.
AB  - We have sequenced the NIb coding region of sugarcane mosaic potyvirus strain SC
      (SCMV-SC) and eight field isolates of SCMV from Australia. This region comprised
      1563 nucleotides and encoded a putative protein of 521 amino acids containing the
      consensus motif GDD. The protease cleavage sites between the NIa/NIb and the
      NIb/coat protein were found to be Q/C and Q/A, respectively. The SCMV sequences
      were most similar to sorghum mosaic potyvirus with identities of 70% and 78% at
      the nucleotide and amino acid levels, respectively. When the sequences were
      compared to each other, there was a maximum of 3.3% variation between isolates at
      the nucleotide level and a maximum of 0.8% at the amino acid level. Phylogenetic
      analysis of the sequences indicated the field isolates were grouped according to
      their geographical location. The SCMV sequence with most homology to all other
      isolates has been selected to generate constructs for replicase-mediated
      resistance.

PMID- 9526538
TI  - The nucleotide sequence of RNA-1 of Indian peanut clump furovius.
AB  - The nucleotide sequence of RNA-1 of an isolate of the H serotype of Indian peanut
      clump virus (IPCV-H) was shown to comprise 5,841 nucleotides. The RNA contains
      three open reading frames (ORF) which are between nucleotides 133 and 3,522,
      nucleotides 3,526 and 5,103 (assuming expression by suppression of the ORF 1
      termination codon) and nucleotides 5,168 and 5,539. The encoded polypeptides have
      M(r), of 129,687 (p130), 60,188 (p60) and 14,281 (p14). ORF 2 is thought to be
      expressed by suppression of the termination codon of ORF 1 to produce a M(r)
      189,975 product (p190). p130 contains sequences characteristic of proteins with
      methyl transferase and NTP-binding properties and p190 contains these and
      sequences characteristic of RNA-dependent RNA polymerases. The nucleotide
      sequence of IPCV RNA-1 is similar to that of peanut clump virus (PCV) and
      corresponding encoded polypeptides are 88% (p130), 95% p60 and 75% (p14)
      identical. The sequences of the translation products are also similar to those of
      soil-borne wheat mosaic virus and barley stripe mosaic virus. Oligonucleotide
      primers, designed on the basis of the sequences of RNA-1 of IPCV and PCV, were
      effective in reverse transcription-PCR amplification of these RNAs and that of
      IPCV isolates of the serologically distinct L and T serotypes.

PMID- 9526539
TI  - Immunological response of mice to the bovine respiratory syncytial virus fusion
      glycoprotein expressed in recombinant baculovirus infected insect cells.
AB  - Bovine respiratory syncytial virus (BRSV) is a major cause of respiratory disease
      in calves. The BRSV genome encodes two major glycoproteins, G and F, which are
      the major targets for the host antibody response. We have expressed the F
      glycoprotein in insect cells (Sf9) using a recombinant baculovirus vector. A
      comparison of the F protein expressed in mammalian and insect cells by SDS-PAGE
      showed that only part of the baculovirus-produced protein was soluble and
      processed like the native protein. The antigenicity of the soluble form of the F
      protein expressed in insect cells was identical to that of the F protein
      expressed in mammalian cells. Immunization with the F protein expressed in insect
      cells induced neutralizing antibodies in mice. This antigenic preparation
      adjuvanted with Quil-A produced an increased neutralizing antibody titer and
      induced protection.

PMID- 9526540
TI  - Modes of Seoul virus infections: persistency in newborn rats and transiency in
      adult rats.
AB  - To understand the mode of persistent infection of Seoul virus in rodents, we
      examined the distribution of the virus genome and antibody production in infected
      rats. When 1-day-old rats were inoculated with the KI-83-262 strain, the S
      segment of viral genome was detected in sera, clots, lungs and kidneys from 3 to
      184 days post inoculation (d.p.i.) by nested reverse transcriptase PCR. On the
      other hand, when 7-week-old rats were infected with this virus, viral genome was
      detected only in the lungs from 3 to 50 d.p.i. The neutralizing antibody titers
      of rats inoculated at 1-day of age were higher than those of rats inoculated at 7
      weeks of age. In both age groups, however, the IgG avidity of antibody increased
      along with the course of infection. We found that urban rats (Rattus norvegicus)
      infected early in life harbored the virus for more than 6 months.

PMID- 9526541
TI  - Vaccine efficacy of recombinant feline herpesvirus type 1 expressing immunogenic
      proteins of feline calicivirus in cats.
AB  - We previously constructed a recombinant feline herpesvirus type 1 (FHV1),
      C7301dlTK-Cap, which contains an entire open reading frame encoding the capsid
      protein of feline calicivirus (FCV) F4 strain in the deleted locus of the
      thymidine kinase (TK) deficient mutant (C7301dlTK) of FHV1. In this report, we
      carried out in vivo experiments to assess the vaccine efficacy of the recombinant
      C7301dlTK-Cap against FCV and FHV1 infections in cats. As a result, two
      vaccinations with the C7301dlTK-Cap by intraocular, intranasal and oral routes
      protected cats to a significant degree against subsequent virulent challenges
      with both parent FCV F4 and FHV1 C7301 strains. The results are applicable for
      the further development of a new genetically engineered polyvalent vaccine for
      cats.

PMID- 9526542
TI  - Characterization of human rotavirus genotype P[8]G5 from Brazil by probe
      hybridization and sequence.
AB  - We report the molecular characterization of rotavirus genotype P[8]G5 strains
      found in fecal specimens collected in four different regions of Brazil, using
      digoxigenin(dig)-labeled oligonucleotide probes, sequence analysis, and RNA-RNA
      hybridization. The closest sequence relationships of the neutralization antigens
      of these strains were to the VP4 protein of P1A[8]G1 strain KU (93.3% identity in
      amino acids 11 to 282) and to the VP7 protein of G serotype 5 strain OSU (87.6%
      identity in amino acids 8 to 232). Based on VP7 sequence differences, we designed
      dig-probes that allowed us to discriminate porcine OSU-like strains from G5
      strains isolated from Brazilian infants. The genetic relationships of two P[8]G5
      isolates to other rotavirus genogroups were analyzed by RNA-RNA hybridization
      with [32P]-GTP probes representative of serotypes P1A[8]G1 (Wa), P[8]G3 (AU17),
      and P9[7]G5 (OSU). The Brazilian P[8]G5 strains showed sequence homology with
      genes of Wa-like and OSU-like strains, suggesting that these two strains were
      naturally occurring reassortants between members of the Wa and porcine rotavirus
      genogroups. The identification of these strains in diverse geographic areas of
      Brazil underscores their stability and demonstrates the emergence of clinically
      important rotavirus diarrhea strains by reassortment.

PMID- 9526544
TI  - Characterization, nucleotide sequence and genome organization of leek white
      stripe virus, a putative new species of the genus Necrovirus.
AB  - White stripe is a disease affecting leek in France with which an isometric virus
      c. 30 nm in diameter is associated. The most evident symptom is the presence of
      white stripes on the leaves extending to the stem. Attempts to demonstrate
      transmission through the soil by sowing or transplanting leek in contaminated
      soil were unsuccessful. The virus was transmitted by sap inoculation to a narrow
      range of herbaceous hosts, all of which were infected only locally. Virus
      purification was from infected leek tissues, where it accumulated in large
      amounts, as demonstrated by ultrastructural observations. RNA was extracted from
      purified virus preparations and cDNA clones were prepared. The complete
      nucleotide sequence of the viral RNA was determined: The genome is 3,662
      nucleotides long and contains five open reading frames (ORFs). The first (ORF 1)
      encodes a putative translation product of M(r) 23,803 (p24) and read through of
      its amber stop codon results in a protein of M(r) 82,625 (p83) (ORF 2). ORF 3 and
      ORF 4 encode two small polypeptides of M(r) 11,280 (p11) and M(r) 6,261 (p6),
      respectively. ORF 5 encodes the capsid protein of M(r) 27,460 (p27). The genome
      organization and sequence alignments with the corresponding products of
      necroviruses suggest that the virus isolated from leek is a new species in the
      genus Necrovirus, for which the name of leek white stripe virus (LWSV) is
      proposed.

PMID- 9526543
TI  - Rotavirus G and P types circulating in Brazil: characterization by RT-PCR, probe
      hybridization, and sequence analysis.
AB  - We used reverse transcription-polymerase chain reaction (RT-PCR) to determine the
      P and G genotypes of 130 culture-adapted rotavirus strains isolated from 181
      fecal specimens of children under 5 years of age from 9 states and the Federal
      District of Brazil. The 4 genotypes found most commonly worldwide were also
      common in Brazil and P[8]G1 was the most prevalent (43%), followed by P[4]G2
      (12%), P[8]G3 (6%), and P[8]G4 (6%). However, unusual types P[8]G5, P[6]G2,
      P[9]G1, P[9]G3, and mixed infections were responsible for 12% and 21% of the
      cases, respectively. Genotype G5 strains were detected in specimens collected in
      all 9 areas surveyed from all 4 regions of Brazil. The unusual strain diversity
      in Brazil suggests that when tetravalent rotavirus vaccines currently being
      developed are introduced into Brazil, laboratory surveillance will be essential
      to monitor protection against unusual strains, particularly those of genotype 5,
      as well as emergence of novel reassortants that may evolve from the large pool of
      children with mixed infections.

PMID- 9526545
TI  - Physical and genetic maps of the human herpesvirus 7 strain SB genome.
AB  - Human herpesvirus 7 (HHV-7) is a close relative of human herpesvirus 6A (HHV-6A)
      and human herpesvirus 6B (HHV-6B) based on limited biologic and genetic data. In
      this work we describe physical and genetic maps for HHV-7 strain SB [HHV-7(SB)],
      which was obtained from the saliva of a healthy adult. The HHV-7(SB) genome
      length is approximately 144 kb by clamped homogeneous electric field gel
      electrophoresis and approximately 135 kb by summation of restriction endonuclease
      fragments. We constructed plasmid clones and PCR amplimers that span the HHV-7
      genome, except for the genomic termini, and determined the maps of the
      restriction endonuclease cleavage sites for BamHI, PstI, and SacI. The HHV-7(SB)
      genome is composed of a single unique region of approximately 122 kb bounded at
      each end by a 6 kb direct repeat. Homologs to thirty-five herpesvirus genes were
      identified. The highest similarity was with the HHV-6 genes, with an average
      amino acid identity of 50%, followed by the human cytomegalovirus counterpart.
      The genomic and genetic maps indicated that the HHV-7 and HHV-6 genomes are
      colinear. There was no sequence variation in a segment of the gene encoding the
      DNA polymerase-associated factor homolog among six HHV-7 isolates, while the
      corresponding segment of the HHV-6A and HHV-6B counterparts differed by 4.6%.
      These data support previous observations that the closest genetic relatives of
      HHV-7 are betaherpesviruses.

PMID- 9526546
TI  - Identification and characterization of the guinea-pig cytomegalovirus
      glycoprotein H gene.
AB  - Subunit vaccines which target viral envelope glycoproteins offer promise for the
      prevention of congenital cytomegalovirus (CMV) infection. The guinea pig model of
      CMV infection is uniquely well suited to testing vaccines for prevention of
      congenital infection, since, in contrast to other animal cytomegaloviruses, the
      guinea pig CMV (GPCMV) crosses the placenta, producing intrauterine infection.
      Antibody to the CMV glycoproteins B (gB) and H (gH) appears to be important in
      conferring protective immunity. Unfortunately, little is known about specific
      GPCMV envelope glycoproteins. Sequencing of GPCMV genome fragments was therefore
      undertaken to test whether GPCMV encodes a gH homologue. Partial sequencing of
      the Hind III A fragment of the GPCMV genome revealed an open reading frame of
      2,169 nucleotides capable of encoding a protein of 723 amino acids. Computer
      matrix analyses demonstrated identity between this ORF and the gH coding
      sequences of other herpesviruses. The GPCMV gH ORF encodes 12 highly conserved
      cysteine residues, contains 9 potential N-linked glycosylation sites, and has a
      predicted M(r) of 81.6 kDa. Northern blot hybridizations with gH-specific probes
      identified an abundant 5.1 kb mRNA with expression kinetics of an "early" gene. A
      polyclonal antiserum raised against a synthetic peptide derived from the deduced
      amino acid sequence of the gH ORF identified a virion-associated protein with an
      approximate M(r) of 85-kDa, the putative GPCMV gH, in immunoblot assays.

PMID- 9526547
TI  - A strain-type clustering of potato virus Y based on the genetic distance between
      isolates calculated by RFLP analysis of the amplified coat protein gene.
AB  - Potato virus Y (PVY) isolates have been classified into genetic strains by a host
      independent criterion using a molecular typing method. The method used extracts
      from infected tissue, and included immunocapture-RT-PCR-RFLP analysis using 5
      different restriction endonucleases (Dde I, Eco RV, Hinf I, Rsa I and Taq I).
      Genetic distances between the different PVY "restrictotypes" were calculated and
      used to define the PVY genetic strains. Three main clusters were found: PVYO,
      PVYN, and non-potato PVY (PVYNP), in good agreement with classical PVY strain
      definitions that combine different biological criteria. Our approach was
      incomparably quicker and more reliable and reproducible than biotyping. The
      potential of this approach for very quick, simple and automatable molecular
      epidemiological studies is discussed.

PMID- 9526548
TI  - Partial characterization of the genome of nine animal caliciviruses.
AB  - Caliciviruses (CVs) include at least 42 distinct serotypes. Seventeen CV
      serotypes have been isolated from marine sources and are called San Miguel sea
      lion caliciviruses (SMSVs). CVs also have been isolated from reptiles, primates,
      and other terrestrial animals. Nucleotide sequences from portions of genome of
      prototype strains for six SMSV serotypes, the reptile CV, Cro-1, the cetacean CV,
      Tur-1, and the primate CV, Pan-1, are presented. cDNA products of the polymerase
      (all strains characterized) and capsid (SMSV-17) regions were produced by reverse
      transcription-polymerase chain reaction using Pan-1 primers. Comparisons of
      nucleotide and amino acid identity among these and published CV sequences
      indicated that the nine characterized CVs fall into a phylogenetic group that
      includes SMSV-1 and SMSV-4 and that is more closely related to other
      characterized animal CVs than to most human CVs. The phylogenetic analysis also
      indicated that distinct genera exist among the Caliciviridae. SMSV-17 and SMSV-4
      are predicted to be closer to each other than other caliciviruses of known
      serotype; 574 (82%) of the 704 amino acids in the SMSV-17 and SMSV-4 capsid genes
      were identical.

PMID- 9526549
TI  - Functional expression of the bovine herpesvirus 1 alkaline deoxyribonuclease
      (UL12) in Escherichia coli.
AB  - Sequence analysis within the unique long segment of the bovine herpesvirus 1 (BHV
      1; infectious bovine rhinotracheitis virus) genome identified an open reading
      frame whose deduced protein product of 487 amino acids exhibited homology to
      alkaline deoxyribonucleases (DNases) of other herpesviruses. To determine this
      BHV-1 gene product has nuclease activity, the gene designated UL12 was inserted
      into the vector pET-28a(+) and expressed in Escherichia coli as an oligohistidine
      tagged protein. Upon induction with isopropyl beta-D-thiogalactopyranoside E.
      coli BL21 (DE3) [pLysS] cells carrying this recombinant plasmid produced a 57-kDa
      protein, the molecular mass of which was in accordance with the prediction from
      the DNA sequence. The recombinant UL12 protein purified by nickel-chelating
      affinity chromatography exhibited both exonuclease and endonuclease activity,
      each with an alkaline pH optimum.

PMID- 9526550
TI  - B-cell epitopes of varicella-zoster virus glycoprotein II.
AB  - B-cell epitopes of varicella-zoster virus glycoprotein II were mapped by means of
      solid phase ELISA, synthetic oligopeptides (constructed according to the Davison
      Scott sequencing of the varicella-zoster virus genome) and sera from varicellae
      and herpes zoster patients. The individual pattern of antibody peptide binding
      varied considerably but at least 9 more reactive sites seemed discernible. A 31
      mer-peptide corresponding to a hydrophilic segment of the glycoprotein (aa 417
      447) was constructed. This peptide reacted with 2 out of 4 varicellae and 5 out
      of 9 zoster sera, respectively.

PMID- 9526552
TI  - Recent revisions of the rules of virus classification and nomenclature.

PMID- 9526553
TI  - Acetamidine lysine derivative, N-(5(S)-amino-6,7-dihydroxyheptyl)ethanimidamide
      dihydrochloride: a highly selective inhibitor of human inducible nitric oxide
      synthase.

PMID- 9526551
TI  - Sequence variation in 5' termini of rubella virus genomes: changes affecting
      structure of the 5' proximal stem-loop.
AB  - Variation within a 523 nucleotide region proximal to the 5' terminus of seven
      rubella virus strains has been analysed. Compared to the Therien strain twenty
      sites of nucleotide variation have been identified, three of which are in the 5'
      untranslated region. Individual strains have between three and nine nucleotide
      differences, only three of which result in amino acid substitutions. TO-336 has a
      serine for threonine at amino acid (aa) 42 and CM arginine for histidine at aa
      159. RA27/3 has arginine for lysine at aa 3 and serine for threonine at aa 42.
      Nucleotide differences which affect a stem-loop structure reported to be
      important for binding of host cell proteins have been identified.

PMID- 9526554
TI  - High-affinity aptamers selectively inhibit human nonpancreatic secretory
      phospholipase A2 (hnps-PLA2).
AB  - A family of sequence-related 2'-aminopyrimidine, 2'-hydroxylpurine aptamers,
      developed by oligonucleotide-based combinatorial chemistry, SELEX (systematic
      evolution of ligand by exponential enrichment) technology, binds human
      nonpancreatic secretory phospholipase A2 (hnps-PLA2) with nanomolar affinities
      and inhibits enzymatic activity. Aptamer 15, derived from the family, binds hnps
      PLA2 with a Kd equal to 1.7 +/- 0.2 nM and, in a standard chromogenic assay of
      enzymatic activity, inhibits hnps-PLA2 with an IC50 of 4 nM, at a mole fraction
      of substrate concentration of 4 x 10(-6) and a calculated Ki of 0.14 nM. Aptamer
      15 is selective for hnps-PLA2, having a 25- and 2500-fold lower affinity,
      respectively, for the unrelated proteins human neutrophil elastase and human IgG.
      Contractions of guinea pig lung pleural strips induced by hnps-PLA2 are abolished
      by 0.3 microM aptamer 15, whereas contractions induced by arachidonic acid are
      not altered. The structure that is essential for binding and inhibition appears
      to be a 40-base hairpin/loop motif with an asymmetrical internal loop. The
      affinity and activity of the aptamers demonstrate the ability of the SELEX
      process to isolate antagonists of nonnucleic-acid-binding proteins from vast
      oligonucleotide combinatorial libraries.

PMID- 9526556
TI  - Dihydropyrancarboxamides related to zanamivir: a new series of inhibitors of
      influenza virus sialidases. 2. Crystallographic and molecular modeling study of
      complexes of 4-amino-4H-pyran-6-carboxamides and sialidase from influenza virus
      types A and B.
AB  - The first paper in this series (see previous article) described structure
      activity studies of carboxamide analogues of zanamivir binding to influenza virus
      sialidase types A and B and showed that inhibitory activity of these compounds
      was much greater against influenza A enzyme. To understand the large differences
      in affinities, a number of protein-ligand complexes have been investigated using
      crystallography and molecular dynamics. The crystallographic studies show that
      the binding of ligands containing tertiary amide groups is accompanied by the
      formation of an intramolecular planar salt bridge between two amino acid residues
      in the active site of the enzyme. It is proposed that the unexpected strong
      binding of these inhibitors is a result of the burial of hydrophobic surface area
      and salt-bridge formation in an environment of low dielectric. In sialidase from
      type A virus, binding of the carboxamide moeity and salt-bridge formation have
      only a minor effect on the positions of the surrounding residues, whereas in type
      B enzyme, significant distortion of the protein is observed. The results suggest
      that the decreased affinity in enzyme from influenza B is directly correlated
      with the small changes that occur in the amino acid residue interactions
      accompanying ligand binding. Molecular dynamics calculations have shown that the
      tendency for salt-bridge formation is greater in influenza A sialidase than
      influenza B sialidase and that this tendency is a useful descriptor for the
      prediction of inhibitor potency.

PMID- 9526555
TI  - Dihydropyrancarboxamides related to zanamivir: a new series of inhibitors of
      influenza virus sialidases. 1. Discovery, synthesis, biological activity, and
      structure-activity relationships of 4-guanidino- and 4-amino-4H-pyran-6
      carboxamides.
AB  - 4-Amino- and 4-guanidino-4H-pyran-6-carboxamides 4 and 5 related to zanamivir
      (GG167) are a new class of inhibitors of influenza virus sialidases. Structure-
      activity studies reveal that, in general, secondary amides are weak inhibitors of
      both influenza A and B viral sialidases. However, tertiary amides, which contain
      one or more small alkyl groups, show much greater inhibitory activity,
      particularly against the influenza A virus enzyme. The sialidase inhibitory
      activities of these compounds correlate well with their in vitro antiviral
      efficacy, and several of the most potent analogues displayed useful antiviral
      activity in vivo when evaluated in a mouse model of influenza A virus infection.
      Carboxamides which were highly active sialidase inhibitors in vitro also showed
      good antiviral activity in the mouse efficacy model of influenza A infection when
      administered intranasally but displayed modest activity when delivered by the
      intraperitoneal route.

PMID- 9526557
TI  - (E)-3-(2-(N-phenylcarbamoyl)vinyl)pyrrole-2-carboxylic acid derivatives. A novel
      class of glycine site antagonists.
AB  - The synthesis and preliminary biological evaluation of novel (E)-3-(2-(N
      phenylcarbamoyl)-vinyl)pyrrole-2-carboxylic acids bearing alkyl, acyl, alkoxy,
      phenyl, and halo substituents at the 4- and 5-positions of the pyrrole ring are
      reported. These compounds were studied for their in vitro affinity at the
      strychnine-insensitive glycine-binding site of the N-methyl-D-aspartate (NMDA)
      receptor complex. In the [3H]glycine binding assay (E)-4,5-dibromo-3-(2-(N
      phenylcarbamoyl)vinyl)pyrrole-2-carboxylic acid 6w (pKi = 7.95 +/- 0.01) and the
      4-bromo-5-methyl 6j (pKi = 7.24 +/- 0.01) and 4,5-dimethyl 6g (pKi = 6.70 +/-
      0.03) analogues were the most active compounds of the series. Qualitative
      structure-activity analysis points to a negative correlation between bulk of the
      C-4 and C-5 substituents and affinity which is enhanced by halo-substituents.
      QSAR analysis by the Hansch descriptors F, R, pi, and MR, on a subset of
      compounds with pKi > or = 4, indicates that electron-withdrawing groups at C-4
      and C-5 enhance the affinity. Bulk and lipophilicity are also relevant for the
      substituents at these positions. 6g was found to be a full antagonist (alpha = 0;
      enhancement of the [3H]TCP binding). The in vivo potency of 6g, 6j, and 6w was
      evaluated by the inhibition of NMDA-induced convulsions in mice by both the i.v.
      and po routes; 6w was the most active compound (ED50 = 3 x 10(-3) (0.8-10) g/kg,
      i.v. and 30 x 10(-3) (4.5-61) g/kg, p.o.). The results of this study indicate
      that the 3,4-disubstitutedpyrrole-2-carboxylate represents a novel template for
      the design of new glycine antagonists.

PMID- 9526559
TI  - Comparative binding energy analysis of HIV-1 protease inhibitors: incorporation
      of solvent effects and validation as a powerful tool in receptor-based drug
      design.
AB  - A comparative binding energy (COMBINE) analysis (Ortiz et al. J. Med. Chem. 1995,
      38, 2681-2691) has been performed on a training set of 33 HIV-1 protease
      inhibitors, and the resulting regression models have been validated using an
      additional external set of 16 inhibitors. This data set was originally reported
      by Holloway et al. (J. Med. Chem. 1995, 38, 305-317), who showed the usefulness
      of molecular mechanics interaction energies for predicting the activity of novel
      HIV-1 protease inhibitors within the framework of the MM2X force field and linear
      regression techniques. We first used the AMBER force field on the same set of
      three-dimensional structures to check up on any possible force-field
      dependencies. In agreement with the previous findings, the calculated raw ligand
      receptor interaction energies were highly correlated with the inhibitory
      activities (r2 = 0.81), and the linear regression model relating both magnitudes
      had an acceptable predictive ability both in internal validation tests (q2 =
      0.79, SDEPcv = 0.61) and when applied to the external set of 16 different
      inhibitors (SDEPex = 1.08). When the interaction energies were further analyzed
      using the COMBINE formalism, the resulting PLS model showed improved fitting
      properties (r2 = 0.89) and provided better estimations for the activity of the
      compounds in the external data set (SDEPex = 0.83). Computation of the
      electrostatic part of the ligand-receptor interactions by numerically solving the
      Poisson-Boltzmann equation did not improve the quality of the linear regression
      model. On the contrary, incorporation of the solvent-screened residue-based
      electrostatic interactions and two additional descriptors representing the
      electrostatic energy contributions to the partial desolvation of both the ligands
      and the receptor resulted in a COMBINE model that achieved a remarkable
      predictive ability, as assessed by both internal (q2 = 0.73, SDEPcv = 0.69) and
      external validation tests (SDEPex = 0.59). Finally, when all the inhibitors
      studied were merged into a single expanded set, a new model was obtained that
      explained 91% of the variance in biological activity (r2 = 0.91), with very high
      predictive ability (q2 = 0.81, SDEPcv = 0.66). In addition, the COMBINE analysis
      provided valuable information about the relative importance of the contributions
      to the activity of individual residues that can be fruitfully used to design
      better inhibitors. All in all, COMBINE analysis is validated as a powerful
      methodology for predicting binding affinities and pharmacological activities of
      congeneric ligands that bind to a common receptor.

PMID- 9526558
TI  - 1,4-Cyclohexanecarboxylates: potent and selective inhibitors of
      phosophodiesterase 4 for the treatment of asthma.
AB  - Evaluation of a variety of PDE4 inhibitors in a series of cellular and in vivo
      assays suggested a strategy to improve the therapeutic index of PDE4 inhibitors
      by increasing their selectivity for the ability to inhibit PDE4 catalytic
      activity versus the ability to compete for high affinity [3H]rolipram-binding
      sites in the central nervous system. Use of this strategy led ultimately to the
      identification of cis-4-cyano-4-[3-(cyclopentyloxy)-4-methoxyphenyl]cyclohexane-1
      carboxyl ic acid (1, SB 207499, Ariflo), a potent second-generation inhibitor of
      PDE4 with a decreased potential for side effects versus the archetypic first
      generation inhibitor, (R)-rolipram.

PMID- 9526560
TI  - Molecular properties and pharmacokinetic behavior of cetirizine, a zwitterionic
      H1-receptor antagonist.
AB  - The ionization and lipophilicity behavior of the antihistamine (H1-receptor
      antagonist) cetirizine was investigated, showing the drug to exist almost
      exclusively as a zwitterion in the pH region 3.5-7.5. In this pH range, its
      octanol/water lipophilicity is constant and low compared to cationic
      antihistamines (log D = log PZ = 1.5), whereas its H-bonding capacity is
      relatively large (delta log PZ > or = 3.1). Conformational, electronic, and
      lipophilicity potential calculations revealed that zwitterionic cetirizine
      experiences partial intramolecular charge neutralization in folded conformers of
      lower polarity. Pharmacokinetic investigations have shown the drug to be highly
      bound to blood proteins, mainly serum albumin, and to have a low brain uptake,
      explaining its lack of sedative effects. As such, cetirizine does not differ from
      "second-generation" antihistamines. In contrast, its very low apparent volume of
      distribution in humans (0.4 L kg-1, smaller than that of exchangeable water)
      implies a low affinity for lean tissues such as the myocardium and is compatible
      with the absence of cardiotoxicity of the drug. The zwitterionic nature and
      modest lipophilicity of cetirizine may account for this pharmacokinetic behavior.
      The suggestion is offered that cetirizine and analogous zwitterions, whose
      physicochemical, pharmacokinetic, and pharmacodynamic properties differ from
      those of "first-" and "second-generation" drugs in this class, could be
      considered as "third-generation" antihistamines.

PMID- 9526561
TI  - (-)-3 beta-Substituted ecgonine methyl esters as inhibitors for cocaine binding
      and dopamine uptake.
AB  - Ten 3 beta-ecgonine analogues were synthesized and characterized by 1H and 13C
      NMR, MS, and elemental analysis. The compounds were synthesized as (-)
      stereoisomers from (-)-cocaine. These compounds were assessed for their ability
      to inhibit [3H]cocaine binding to rat striatal tissue and to inhibit [3H]DA
      uptake into rat striatal synaptosomes. In this series of compounds, the length of
      the spacer between the aryl group and the tropane skeleton ranged from 1 to 4
      bond distances, and conformational flexibility of the linkage and orientation of
      the aryl ring system were controlled by various types of linkages. The most
      potent of the analogues was methyl-(1R-2-exo-3-exo)-8-methyl-3-(beta-styrenyl)-8
      azabicyclo[3. 2.1] octane-2-carboxylate. One of the less potent compounds was
      found to inhibit [3H]cocaine binding and [3H]DA uptake with significantly
      different IC50 values, in contrast to 14 other 3 beta-substituted analogues.
      Molecular modeling and CoMFA analysis were used to obtain a rigorous structure
      function relationship for the studied compounds. The results showed that the
      potencies of these 3 beta-substituted ecgonine methyl esters were dominated by
      steric effects and were acutely sensitive to the distance between the aryl ring
      and the tropane skeleton and to the orientation of the aryl ring system relative
      to the tropane skeleton. The current study provides a clearer picture of the
      shape and size of the putative hydrophobic binding pocket for the 3 beta
      substituent at the cocaine receptor as well as emphasizing the importance of a
      drug's free energy of solvation in obtaining structure-activity relationships.

PMID- 9526562
TI  - Inhibitors of farnesyl protein transferase. 4-Amido, 4-carbamoyl, and 4
      carboxamido derivatives of 1-(8-chloro-6,11-dihydro-5H-benzo[5,6]- cyclohepta[1,2
      b]pyridin-11-yl)piperazine and 1-(3-bromo-8-chloro-6,11- dihydro-5H
      benzo[5,6]cyclohepta[1,2-b]pyridin-11-yl)piperazine.
AB  - The synthesis of a variety of novel 4-amido, 4-carbamoyl and 4-carboxamido
      derivatives of 1-(8-chloro-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11
      yl) piperazine to explore the SAR of this series of FPT inhibitors is described.
      This resulted in the synthesis of the 4- and 3-pyridylacetyl analogues 45a and
      50a, respectively, both of which were orally active but were found to be rapidly
      metabolized in vivo. Identification of the principal metabolites led to the
      synthesis of a variety of new compounds that would be less readily metabolized,
      the most interesting of which were the 3- and 4-pyridylacetyl N-oxides 80a and
      83a. Novel replacements for the pyridylacetyl moiety were also sought, and this
      resulted in the discovery of the 4-N-methyl and 4-N-carboxamidopiperidinylacetyl
      derivatives 135a and 160a, respectively. All of these derivatives exhibited
      greatly improved pharmacokinetics. The synthesis of the corresponding 3-bromo
      analogues resulted in the discovery of the 4-pyridylacetyl N-oxides 83b (+/-) and
      85b [11S(-)] and the 4-carboxamidopiperidinylacetamido derivative 160b (+/-), all
      of which exhibited potent FPT inhibition in vitro. All three showed excellent
      oral bioavailability in vivo in nude mice and cynomolgus monkeys and exhibited
      excellent antitumor efficacy against a series of tumor cell lines when dosed
      orally in nude mice.

PMID- 9526563
TI  - Ethnobotanical-directed discovery of the antihyperglycemic properties of
      cryptolepine: its isolation from Cryptolepis sanguinolenta, synthesis, and in
      vitro and in vivo activities.
AB  - Using an ethnobotanical approach in combination with in vivo-guided fractionation
      as a means for lead discovery, cryptolepine was isolated as an antihyperglycemic
      component of Cryptolepis sanguinolenta. Two syntheses of cryptolepine, including
      an unambiguous synthesis, are reported. The hydroiodide, hydrochloride, and
      hydrotrifluoromethanesulfonate (hydrotriflate) salts of cryptolepine were
      synthesized, and a comparison of their spectral properties and their in vitro
      activities in a 3T3-L1 glucose transport assay is made. Cryptolepine and its salt
      forms lower blood glucose in rodent models of type II diabetes. While a number of
      bioactivities have been reported for cryptolepine, this is the first report that
      cryptolepine possesses antihyperglycemic properties.

PMID- 9526565
TI  - 2,4-Diamino-6,7-dihydro-5H-cyclopenta[d]pyrimidine analogues of trimethoprim as
      inhibitors of Pneumocystis carinii and Toxoplasma gondii dihydrofolate reductase.
AB  - Three previously unreported (R,S)-2,4-diamino-5-[(3,4,5-trimethoxyphenyl) alkyl]
      6,7-dihydro-5H-cyclopenta[d]pyrimidines 15a-c were synthesized as analogues of
      trimethoprim (TMP) and were tested as inhibitors of Pneumocystis carinii,
      Toxoplasma gondii, and rat liver dihydrofolate reductase (DHFR). The length of
      the alkyl bridge between the cyclopenta[d]pyrimidine and trimethoxyphenyl moiety
      ranged from one in 15a to three carbons in 15c. The products were tested as
      competitive inhibitors of the reduction of dihydrofolate by Pneumocystis carinii,
      Toxoplasma gondii, and rat liver DHFR. Compounds 15a-c had IC50 values of > 32,
      1.8 and 1.3 microM, respectively, against P. carinii DHFR, as compared to 12
      microM for TMP. Against the T. gondii enzyme, 15a-c had IC50 values of 21, 0.14
      and 0.14 microM, respectively, as compared to 2.7 microM for TMP. Inhibitors 15b
      and 15c with two- and three-carbon bridges were significantly more potent than
      15a against all three enzymes. Unlike TMP, 15b and 15c were better inhibitors of
      the rat liver enzyme than of the microbial enzymes. The potency of 15b and 15c
      against rat liver DHFR was less than has been reported for the corresponding 6,7
      dihydro-5H-cyclopenta[d]pyrimidines with a classical p-aminobenzoyl-L-glutamate
      side chain as inhibitors of bovine, murine, and human DHFR.

PMID- 9526564
TI  - Novel 17-azolyl steroids, potent inhibitors of human cytochrome 17 alpha
      hydroxylase-C17,20-lyase (P450(17) alpha): potential agents for the treatment of
      prostate cancer.
AB  - A new synthetic route to a variety of novel delta 16-17-azolyl steroids is
      described: it involves the nucleophilic vinylic "addition-elimination"
      substitution reaction of 3 beta-acetoxy-17-chloro-16-formylandrosta-5,16-diene
      (2) and azolyl nucleophiles. Some of these novel delta 16-17-azolyl steroids, 6,
      17, 19, and 27-29, prepared in good overall yields, are very potent inhibitors of
      human and rat testicular P450(17) alpha. They are shown to be noncompetitive and
      appear to be slow-binding inhibitors of human P450(17) alpha. The most potent
      compounds are 3 beta-hydroxy-17-(1H-imidazol-1-yl)androsta-5,16-diene (17), 3
      beta-hydroxy-17-(1H-1,2,3-triazol-1-yl)androsta-5,-16-diene (19), and 17-(1H
      imidazol-1-yl)androsta-4,16-dien-3-one (28), with Ki values of 1.2, 1.4, and 1.9
      nM, respectively, being 20-32 times more potent than ketoconazole (Ki = 38 nM).
      Spectroscopic studies with a modified form of human P450(17) alpha indicate that
      the inhibition process involves binding of steroidal azole nitrogen to the heme
      iron of the enzyme. Furthermore, some of these potent P450(17) alpha inhibitors
      (27-29) are also powerful inhibitors of steroid 5 alpha-reductase, and others (17
      and 19) appear to exhibit strong antiandrogenic activity in cultures of the LNCaP
      human prostatic cancer cell line. These novel compounds with impressive dual
      biological activities make them strong candidates for development as therapeutic
      agents for treatment of prostate cancer and other disease states which depend on
      androgens.

PMID- 9526566
TI  - A backbone-cyclic, receptor 5-selective somatostatin analogue: synthesis,
      bioactivity, and nuclear magnetic resonance conformational analysis.
AB  - Cyclo(PheN2-Tyr-D-Trp-Lys-Val-PheC3)-Thr-NH2 (PTR 3046), a backbone-cyclic
      somatostatin analogue, was synthesized by solid-phase methodology. The binding
      characteristics of PTR 3046 to the different somatostatin receptors, expressed in
      CHO cells, indicate high selectivity to the SSTR5 receptor. PTR 3046 is highly
      stable against enzymatic degradation as determined in vitro by incubation with
      rat renal homogenate and human serum. The biological activity of PTR 3046 in vivo
      was determined in rats. PTR 3046 inhibits bombesin- and caerulein-induced amylase
      and lipase release from the pancreas without inhibiting growth hormone or
      glucagon release. The major conformation of PTR 3046 in CD3OH, as determined by
      NMR, is defined by a type II' beta-turn at D-Trp-Lys and a cis amide bond at Val
      PheC3.

PMID- 9526567
TI  - Excitatory amino acid receptor ligands: resolution, absolute stereochemistry, and
      enantiopharmacology of 2-amino-3-(4-butyl-3-hydroxyisoxazol-5-yl)propionic acid.
AB  - (RS)-2-Amino-3-(4-butyl-3-hydroxyisoxazol-5-yl)propionic acid (Bu-HIBO, 6) has
      previously been shown to be an agonist at (RS)-2-amino-3-(3-hydroxy-5
      methylisoxazol-4-yl)propionic acid (AMPA) receptors and an inhibitor of CaCl2
      dependent [3H]-(S)-glutamic acid binding (J. Med. Chem. 1992, 35, 3512-3519). To
      elucidate the pharmacological significance of this latter binding affinity, which
      is also shown by quisqualic acid (3) but not by AMPA, we have now resolved Bu
      HIBO via diastereomeric salt formation using the diprotected Bu-HIBO derivative
      11 and the enantiomers of 1-phenylethylamine (PEA). The absolute stereochemistry
      of (S)-Bu-HIBO (7) (ee = 99.0%) and (R)-Bu-HIBO (8) (ee > 99.6%) were established
      by an X-ray crystallographic analysis of compound 15, a salt of (R)-PEA, and
      diprotected 8. Circular dichroism spectra of 7 and 8 were recorded. Whereas 7
      (IC50 = 0.64 microM) and 8 (IC50 = 0.57 microM) were equipotent as inhibitors of
      CaCl2-dependent [3H]-(S)-glutamic acid binding, neither enantiomer showed
      significant affinity for the synaptosomal (S)-glutamic acid uptake system(s).
      AMPA receptor affinity (IC50 = 0.48 microM) and agonism (EC50 = 17 microM) were
      shown to reside exclusively in the S-enantiomer, 7. Compounds 7 and 8 did not
      interact detectably with kainic acid or N-methyl-D-aspartic acid (NMDA) receptor
      sites. Neither 7 nor 8 affected the function of the metabotropic (S)-glutamic
      acid receptors mGlu2 and mGlu4a, expressed in CHO cells. Compound 8 was shown
      also to be inactive at mGlu1 alpha, whereas 7 was determined to be a moderately
      potent antagonist at mGlu1 alpha (Ki = 110 microM) and mGlu5a (Ki = 97 microM).
      Using the rat cortical wedge preparation, the AMPA receptor agonist effect of 7
      was markedly potentiated by coadministration of 8 at 21 degrees C, but not at 2-4
      degrees C. These observations together indicate that the potentiation of the AMPA
      receptor agonism of 7 by 8 is not mediated by metabotropic (S)-glutamate
      receptors but rather by the CaCl2-dependent (S)-glutamic acid binding system,
      which shows the characteristics of a transport mechanism. After intravenous
      administration in mice, 7 (ED50 = 44 mumol/kg) was slightly more potent than AMPA
      (1) (ED50 = 55 mumol/kg) and twice as potent as Bu-HIBO (6) (ED50 = 94 mumol/kg)
      as a convulsant, whereas 8 was inactive. After subcutaneous administration in
      mice, Bu-HIBO (ED50 = 110 mumol/kg) was twice as potent as AMPA (ED50 = 220
      mumol/kg) as a convulsant. Since 7 and Bu-HIBO (EC50 = 37 microM) are much weaker
      than AMPA (EC50 = 3.5 microM) as AMPA receptor agonists in vitro, the presence of
      a butyl group in the molecules of Bu-HIBO and 7 seems to facilitate the
      penetration of these compounds through the blood-brain barrier.

PMID- 9526568
TI  - Orally active antimalarial 3-substituted trioxanes: new synthetic methodology and
      biological evaluation.
AB  - On the basis of a mechanistic understanding of the mode of action of artemisinin
      like antimalarials, a series of structurally simple 3-aryl-1,2,4-trioxanes 5 was
      designed and was prepared in three to five operations from commercial reactants.
      The 3-aryl group was attached in each case as a nucleophile. In an electronically
      complementary fashion, 3-(fluoroalkyl)-trioxanes 6 were prepared via attachment
      of electrophilic fluoroalkyl esters. Both in vitro and in vivo antimalarial
      evaluations of these new trioxanes showed 12 beta-methoxy-3-aryltrioxanes 5g, 5j,
      5k, and 51 to be highly potent, with crystalline fluorobenzyl ether trioxane 5k
      especially potent even when administered to rodents orally. As shown by
      rearrangement of hexamethyl Dewar benzene into hexamethylbenzene, iron-induced
      degradation of some of these 3-aryltrioxanes 5 involves generation of high-valent
      iron oxo species that might kill malaria parasites.

PMID- 9526569
TI  - Design, synthesis, derivatization, and structure-activity relationships of
      simplified, tricyclic, 1,2,4-trioxane alcohol analogues of the antimalarial
      artemisinin.
AB  - Novel C4-(hydroxyalkyl)trioxanes 5d and 5e were designed and synthesized based on
      an understanding of the molecular mechanism of action of similar 1,2,4-trioxanes
      structurally related to the antimalarial natural product artemisinin (1). In
      vitro efficacies of these two new pairs of C4-diastereomers against chloroquine
      sensitive Plasmodium falciparum support conclusions about the importance to
      antimalarial activity of formation of a C4 radical by a 1,5-hydrogen atom
      abstraction. Derivatives 6, 7, and 21 of C4 beta-substituted trioxane alcohols
      4a, 5d, and 5e were prepared, each in a single-step, high-yielding
      transformation. Four of these new analogues, 6a-c and 7, are potent in vitro
      antimalarials, having 140 to 50% of the efficacy of the natural trioxane
      artemisinin (1).

PMID- 9526571
TI  - Discovery of 1-(4-fluorophenyl)-(3R)-[3-(4-fluorophenyl)-(3S)-hydroxypropyl]-(4S)
      (4 -hydroxyphenyl)-2-azetidinone (SCH 58235): a designed, potent, orally active
      inhibitor of cholesterol absorption.
AB  - (3R)-(3-Phenylpropyl)-1,(4S)-bis(4-methoxyphenyl)-2-azetidinone (2, SCH 48461), a
      novel inhibitor of intestinal cholesterol absorption, has recently been described
      by Burnett et al. and has been demonstrated to lower total plasma cholesterol in
      man. The potential sites of metabolism of 2 were considered, and the most
      probable metabolites were prepared. The oral cholesterol-lowering efficacy of the
      putative metabolites was evaluated in a 7-day cholesterol-fed hamster model for
      the reduction of serum total cholesterol and liver cholesteryl esters versus
      control. On the basis of our analysis of the putative metabolite structure
      activity relationship (SAR), SCH 58235 (1, 1-(4-fluorophenyl)-(3R)-[3-(4
      fluorophenyl)-(3S)-hydroxypropyl]-(4S)- (4-hydroxyphenyl)-2-azetidinone) was
      designed to exploit activity enhancing oxidation and to block sites of potential
      detrimental metabolic oxidation. Additionally, a series of congeners of 2 were
      prepared incorporating strategically placed hydroxyl groups and fluorine atoms to
      further probe the SAR of 2-azetidinone cholesterol absorption inhibitors. Through
      the SAR analysis of a series of putative metabolites of 2, compound 1 was
      targeted and found to exhibit remarkable efficacy with an ED50 of 0.04 mg/kg/day
      for the reduction of liver cholesteryl esters in a 7-day cholesterol-fed hamster
      model.

PMID- 9526570
TI  - Intensely potent doxorubicin analogues: structure-activity relationship.
AB  - N-(5,5-Diacetoxypent-1-yl)doxorubicin (1b) is an intensely cytotoxic doxorubicin
      analogue that retains full potency against tumor cells that express elevated
      levels of P-glycoprotein and are resistant to doxorubicin. 1b was designed to be
      hydrolyzed in the presence of carboxylate esterases to N-(5-oxypent-1
      yl)doxorubicin, an aldehyde capable of existing in equilibrium with a cyclic
      carbinolamine. To investigate the structural determinants of potency for 1b, we
      have prepared a series of chemically related compounds in which various omega
      [bis(acetoxy)]alkyl or omega-[bis(acetoxy)]alkoxyalkyl groups are substituted at
      the 3'-amino position of the daunosamine sugar. These groups were selected to
      assess the effect of chain length, oxygen substitution, and carbinolamine ring
      size on analogue potency. The compounds were evaluated for their ability to
      inhibit the in vitro growth of the following cell lines: (a) Chinese hamster
      ovary (CHO) cells, (b) a CHO cell mutant 100-fold resistant to doxorubicin that
      expresses elevated levels of P-glycoprotein, (c) a murine ductal cell pancreatic
      adenocarcinoma (Panc 02), and (d) a murine mammary carcinoma (CA 755). The most
      potent members of the series were those that could form a straight chain aldehyde
      intermediate after esterase-mediated hydrolysis of the omega-bis(acetoxy) groups
      and give rise to 5- or 6-membered ring carbinolamines. Analogues capable of
      forming 7-, 8-, or 9-membered carbinolamines were markedly less active. The N
      methyl derivative of 1b, which cannot give rise to a cyclic carbinolamine, was 2
      orders of magnitude less potent than 1b. A branched chain analogue, 1f, which
      contained a tertiary carbon atom adjacent to the omega-bis(acetoxy) groups, was
      also substantially less active than its nonbranched counterpart, 1a. These
      findings suggest that the chain length of the 3'-amino substituents and the
      ability of the derived aldehydes to form 5- or 6-membered carbinolamines are
      critical determinants of biologic potency.

PMID- 9526572
TI  - Design, synthesis, and evaluation of the multidrug resistance-reversing activity
      of D-glucose mimetics of hapalosin.
AB  - When five substituents of hapalosin were placed on D-glucose, molecular modeling
      revealed that the substituents on mimetics 2 and 3 occupy similar spatial
      positions as the corresponding substituents on hapalosin. Mimetic 3 and all the
      glucopyranoside intermediates generated in its synthesis were assessed for their
      ability to reverse multidrug resistance (MDR) mediated by P-glycoprotein (P-gp)
      or the multidrug resistance-associated protein (MRP). None of the sugar compounds
      were as effective as hapalosin in inhibiting P-gp in cytotoxicity and drug
      accumulation assays using MCF-7/ADR cells. By contrast, four D-glucose compounds
      exhibited similar efficacy as hapalosin in antagonizing MRP in cytotoxicity
      assays with HL-60/ADR cells.

PMID- 9526573
TI  - Molecular features associated with polyamine modulation of NMDA receptors.
AB  - The effect of 1,3-diamines on basal and spermine-stimulated [3H]MK-801 binding
      was investigated. Systematic variations in the molecular parameters revealed
      that, in general, lipophilic 1,3-diamines inhibited and hydrophilic 1,3-diamines
      enhanced [3H]MK-801 binding in the nominal absence of glutamate and glycine.
      Furthermore, 1,3-diamines which were highly monoprotonated at physiologic pH were
      more effective in modulating basal binding (at 100 microM 1,3-diamine) than
      analogues which were mostly diprotonated or unprotonated. Finally, the
      internuclear distance between the amino nitrogens and the extent of modulation of
      basal [3H]MK-801 binding were correlated. Similar, but more modest, effects were
      seen for spermine-enhanced [3H]MK-801 binding. These results are consistent with
      the existence of two polyamine binding sites associated with the NMDA receptor
      complex. One of the sites appears to preferentially recognize lipophilic
      substances while the other favors hydrophilic materials. Both sites appear to
      recognize polyamines with at least one charged (protonated) amino group and one
      uncharged amino group. The distance between amino groups is a determining factor
      as well.

PMID- 9526574
TI  - Novel biologically active nonpeptidic inhibitors of myristoylCoA:protein N
      myristoyltransferase.
AB  - A new class of biologically active nonpeptidic inhibitors of Candida albicans NMT
      has been synthesized starting from the octapeptide ALYASKLS-NH2 (2). The
      synthetic strategy entailed the preparation of novel protected Ser-Lys mimics 9
      and 12 from (S)- or (R)-3-iodotyrosine and then grafting key enzyme recognition
      elements in a stepwise manner. Like 2, compounds 16, 17, and 18 are competitive
      Candida NMT inhibitors that bind to the peptide recognition site of the enzyme.
      Moreover, 16-18 have an affinity comparable to that of 2 even though they are
      devoid of peptide bonds. In contrast to 2, these nonpeptidic inhibitors exhibit
      antifungal activity.

PMID- 9526575
TI  - Synthesis and pharmacological evaluation of ring-methylated derivatives of 3,4
      (methylenedioxy)amphetamine (MDA).
AB  - The three isomeric ring-methylated derivatives of the well-known hallucinogen and
      entactogen MDA (1a) were synthesized and evaluated for pharmacological activity
      as monoamine-releasing agents and as serotonin agonists. The 2-methyl derivative
      2a and the 5-methyl derivative 2b were found to be more potent and more selective
      than the parent compound in inhibiting [3H]-serotonin accumulation in rat brain
      synaptosomal preparations. Their activity in vivo was confirmed in rats trained
      to discriminate serotonin-releasing agents and hallucinogens from saline. The
      results indicate that compounds 2a,b are among the most potent 5-HT-releasing
      compounds known and show promise as lead compounds in the search for
      antidepressant drugs that release serotonin rather than inhibit its uptake.

PMID- 9526576
TI  - Breast cancer prevalence measured by the Lombardy Cancer Registry.
AB  - AIMS AND BACKGROUND: Breast cancer is the most important malignant neoplasm
      affecting women in Western countries. An increasing number of women undergo
      regular medical checkups, especially during the first years following the
      diagnosis. Therefore, from the health planning point of view, it is essential to
      have prevalence measures to furnish estimates for the demands that the health
      care system could possibly undergo. METHODS: By means of PREVAL, a computerized
      program, breast cancer prevalence has been measured in the Varese province using
      incidence and follow-up data from the Lombardy Cancer Registry (LCR). RESULTS:
      During the 1986-1988 period, breast cancer prevalence for patients alive within
      10 years from diagnosis was about 625 per 100,000 resident women. Of these, 54%
      were over 60 years and 9% were under 45 years of age. Patients alive within 2
      years from diagnosis were about 200 per 100,000 residents; considering the 1978
      1980 period, patients alive within 2 years from diagnosis were just 140 per
      100,000 residents. This dramatic increase in breast cancer prevalence is present
      also for long-term survivors (i.e. patients alive at 10-13 years from the
      diagnosis). Extrapolating breast cancer prevalence measured in the Varese
      province to the whole Lombardy region, the expected number of prevalent cases
      alive within 10 years of the diagnosis, presently living in Lombardy, would be
      27,500. LCR's breast cancer prevalence figures were compatible with available
      data provided by the Finnish Cancer Registry. CONCLUSION: Owing to aging of the
      population, the improvement in survival and the increasing incidence, the number
      of prevalent cases will increase. This phenomenon has and will have great
      importance for the health planning.

PMID- 9526577
TI  - Analysis of false-negative and underreported smears in the Florence district
      screening program for cervical carcinoma.
AB  - AIMS AND BACKGROUND: To review false-negative or underreported (reactive changes,
      squamous or glandular atypia) smears performed in women developing histologically
      proven CIN2 or more severe lesions within 24 months and evaluate error causes.
      The study setting was the Florence District cervical cancer population-based
      screening: about 60,000 women age 25-60 years screened per year. METHODS: 118
      false-negative or underreported cases were identified at screening files-cancer
      Registry matching, and the original smears were reviewed by six independent
      readers to judge smear adequacy and error type. RESULTS: Sampling errors
      (reported as inadequate, negative or less severe than CIN1 at review) accounted
      for 74% and screening/interpretation errors (reported as CIN1 or more severe at
      review) accounted for 26% of studied cases. Screening/interpretation errors were
      more likely ascribed to misinterpretation and underreporting than to
      misperception of cellular abnormalities. CONCLUSIONS: Quality control should
      above all address the problem of sampling adequacy. Due to the rarity of
      misperceived abnormalities (true screening errors), manual or automated
      rescreening of negative smears would not be an effective procedure for quality
      control.

PMID- 9526578
TI  - Chemoprevention trial of contralateral breast cancer with fenretinide. Rationale,
      design, methodology, organization, data management, statistics and accrual.
AB  - The Fenretinide (4-HPR) Breast Cancer Study is a randomized multicenter clinical
      trial originally designed and conducted by the investigators of the Istituto
      Nazionale Tumori of Milan. The study is sponsored by the National Cancer
      Institute of Bethesda and by the Italian National Research Council. The trial was
      designed to evaluate the effectiveness of the synthetic retinoid 4-HPR, at a dose
      of 200 mg per os every day for 5 years, in reducing the incidence of
      contralateral breast cancer in a population of patients previously operated on
      for breast cancer. Between 1987 and 1993, the Istituto Nazionale Tumori of Milan
      and 9 other collaborating Centers enrolled 2,972 women between the ages of 30 and
      70 years who had been previously operated on for T1-T2 N- M0 breast cancer. This
      paper describes the rationale, design, methodology, organization, data
      management, statistics and accrual of the participating population.

PMID- 9526579
TI  - Concurrent carboplatin/5FU and radiotherapy compared to radiotherapy alone in
      locally advanced cervical carcinoma: a case-control study.
AB  - AIMS AND BACKGROUND: Despite the introduction of innovative techniques in
      radiotherapy (RT) delivery, no significant improvement in survival has been
      achieved in the last decades. Concurrent chemoradiation therapy (CRT) is one of
      the several avenues being explored to improve the results. METHODS AND STUDY
      DESIGN: Twenty-eight women with locally advanced squamous cell carcinoma of the
      uterine cervix were treated with CRT comprising a combination of external and
      intracavitary RT, along with 3 cycles of 5-fluorouracil (5-FU) and carboplatin.
      Toxicity, pelvic control rate and disease-free survival achieved in this group of
      patients were compared in a case-control study with those of a group of 28
      patients with similar clinico-pathologic characteristics treated with radical RT
      alone at our institution. RESULTS: CRT was well tolerated, with 97% of the
      patients completing the protocol as planned. Acute toxicity, primarily
      hematologic, was significantly (P = 0.05) higher in the cases than in the
      controls (25% vs 3%). One treatment-related death occurred in a stage III patient
      in the CRT group. The median follow-up was 55 months (range, 20-156) in the RT
      group and 20 months (range, 14-46) in the CRT group. Pelvic control rate, disease
      free survival and overall survival were not significantly different in the two
      groups. Estimated 5-year survival rate was 70% and 66% respectively for the RT
      and CRT group. CONCLUSIONS: Concomitant carboplatin/5-FU and radiotherapy is a
      safe and tolerable means of treatment for locally advanced cervical cancer. In
      our study, however, concurrent CRT did not result in a significant improvement in
      pelvic control rate or survival compared to standard conventional radiotherapy.

PMID- 9526580
TI  - The use of granulocyte colony-stimulating factors following peripheral blood
      progenitor cell rescue after high-dose chemotherapy for advanced breast cancer: a
      prospective study.
AB  - The use of high-dose chemotherapy followed by hematopoietic rescue is increasing
      worldwide for solid tumors. Several studies have suggested that the period of
      absolute neutrophil count (ANC, < 500/ml) may be shortened in patients who
      receive peripheral blood progenitor cells (PBPC). To estimate the clinical value
      of granulocyte-colony-stimulating factor, we examined a cohort of 26 consecutive
      patients with advanced breast cancer who received one or two cycles of high-dose
      chemotherapy with PBPC rescue with or without filgrastim. Thirty-five courses of
      high-dose ICE (ifosfamide, carboplatin, etoposide) chemotherapy were administered
      and evaluated. All patients received PBPC rescue. Sixteen patients (21 courses)
      received subcutaneous filgrastim (5 mg/kg) following PBPC infusion. Recovery to >
      or = 500 ANC occurred at a median time of 7 days post PBPC infusion among
      patients who received filgrastim versus 10 days among patients who received
      standard support care only (P < 0.01). The administration of filgrastim was not
      associated with a reduction in the duration of hospitalization, in the total
      number of days on nonprophylactic antibiotics, number of red blood cell
      transfusions, time to platelet engraftment, or number of febrile days. This could
      be the consequence of the high hematopoietic cell dose administered in the study.
      Therefore, any effect of filgrastim was probably masked by the use of a large
      number of PBPC. Larger prospective randomized studies, specifically focused on
      the utility of the administration of growth factors following high-dose
      chemotherapy and PBPC rescue, may be warranted to know whether the administration
      of filgrastim after PBPC transplantation is really necessary.

PMID- 9526582
TI  - Impact of distal clearance margin on oncologic outcome after restorative
      resection of the rectum.
AB  - There is considerable controversy about the distal clearance margin that needs to
      be maintained beyond the extent of a rectal tumor in order to reduce the risk of
      local recurrence. We investigated the rate of local recurrence, distant
      metastases and survival in 87 patients who had undergone radical restorative
      resection of the rectum for cancer and had been followed up for a median period
      of over 6 years, and we analyzed the statistical relation (log-rank test for
      trend) with the length of the distal margin. The distal margin length was divided
      into three categories: 1 cm, 2 cm, and > or = 3 cm. No significant correlation
      was found between the length of the distal clearance margin and the oncologic
      outcome. Taken together, our data suggest that if the resection line distally
      falls on healthy tissue, there is no need to resect additional rectum in order to
      achieve a better outcome.

PMID- 9526581
TI  - Variations in tumor levels of cis-platinum through a course of fractionated
      radiotherapy in patients with non-small cell lung cancer.
AB  - AIMS AND BACKGROUND: Radiation has been shown to affect the uptake of
      micromolecules by the tissues within the radiation fields. We measured tumor drug
      uptake throughout a course of radiotherapy for stage III non-operable non-small
      cell lung cancer (NSCLC). PATIENTS AND METHODS: Thirty patients were treated with
      radiotherapy consisting of 15 fractions of 300 cGy given over 3 weeks. They were
      divided into groups of 2. At 1.5 hr before a given fraction of radiotherapy, one
      group was given i.v. a bolus of 6 mg/m2 CDDP (cis-diamminedichloroplatinum).
      Between 1.5 and 2 hr after radiotherapy, the patients underwent bronchoscopy,
      during which a biopsy was taken from the tumor mass. A similar procedure was
      carried out on a different group of 2 patients at each of the 15 radiotherapy
      fractions. The amount of platinum in the biopsy sample was measured by atomic
      absorption spectroscopy and expressed as ng platinum/mg tissue. In another 13
      patients, a biopsy was taken before beginning the radiotherapy, and they served
      as controls. RESULTS: The quantity of platinum/g of tissue in the patients was 11
      +/- 4.4 ng/mg tissue. During the course of fractionated radiotherapy, the
      quantity of platinum/g of tumor varied considerably between radiotherapy
      fractions. Maximum uptake was at fractions 8 and 9 (92 ng platinum/mg tissue)
      with the minima during the first few fractions and at fractions 10, 11 and 12 (an
      average 20 ng platinum/mg tissue). CONCLUSIONS: The cyclical variations in the
      uptake of CDDP by the tumor tissue during the protracted course of fractionated
      radiotherapy are probably due to the well-known effects of radiation on vascular
      function and capillary permeability. The results may have implications for future
      clinical protocols involving chemo- and radiotherapy for the treatment of the
      disease.

PMID- 9526583
TI  - Management of complications from hepatobiliary surgery using the percutaneous
      transjejunal approach.
AB  - PURPOSE: The work was aimed at presenting the indications, techniques and results
      of the percutaneous transjejunal approach to the biliary tree in patients with
      hepatobiliary complications due to surgery. PATIENTS AND METHODS: Ten patients, 7
      males and 3 females, mean age 50 years (range, 10-62) with hepatico-jejunostomy,
      who developed cholangitis together with jaundice or bile leakage, underwent this
      procedure, performed through the anastomotic loop that was not surgically
      anchored to the abdominal wall in all cases but one. The transjejunal approach
      was chosen because of non-dilated bile ducts in 3 patients, complex pathologic
      situations in 5 patients and to avoid complications to a transplanted liver in 2
      patients. The jejunal loop was identified using CT, US and fluoroscopy in 4
      patients and after its opacification in the remaining 6 (by percutaneous
      transhepatic or intravenous cholangiography or fistulography). RESULTS: The
      procedure was technically and diagnostically successful in all cases. Therapeutic
      procedures (stenting, dilation, litholysis) were also performed using the
      transjejunal approach in 7 patients and in 6 of them complete pathological
      resolution was achieved. There were no complications. CONCLUSIONS: Different
      pathologies of the biliary tree, in patients with bilio-enteric anastomoses, have
      been identified and treated by this technique; they were fistulas, anastomotic
      and/or multiple segmental benign or malignant stenoses of the bile duct, and
      diffuse intrahepatic lithiasis. The procedure was safe and reliable.

PMID- 9526584
TI  - Postsurgical policy in stage I testicular seminoma: cost and benefit of
      prophylactic irradiation in a long-term experience.
AB  - The definitive cure rate for clinical stage 1 testicular seminoma is very close
      to 100%, and prophylactic irradiation of the regional lymph nodes is associated
      with a low morbidity. Nevertheless, in recent years a "wait-and-see" policy has
      been proposed by some researchers. We analysed the cost/benefit ratio of
      radiotherapy (RT) by review of the case histories of 299 patients treated at the
      Department of Radiotherapy of the Istituto Nazionale per lo Studio e la Cura dei
      Tumori in Milan from January 1968 to December 1989. The 5-year overall survival
      was 99% (97.5% at 10 years), while the 10-year disease-free survival was 96%. The
      recurrence rate was 2.3%, but no patient relapsed in the irradiated areas. Acute
      toxicity was very moderate with only 4 (1.3%) serious radiation sequelae
      occurring 6 to 27 years after treatment. However, 9 second malignancies (3%) were
      observed. Lastly, we have calculated the costs for our National Health Service
      comparing surveillance policy and prophylactic irradiation.

PMID- 9526585
TI  - Prognostic factors of cervical lymph node metastasis in head and neck squamous
      cell carcinoma.
AB  - AIMS AND BACKGROUND: The metastatic spread of squamous cell carcinoma of the head
      and neck (SCCHN) to the cervical lymph nodes is a negative prognostic factor in
      terms of survival. We have used multivariate analysis to identify the possible
      prognostic significance of a number of clinical and pathological characteristics
      in relation to possible involvement of the cervical lymph nodes in a series of
      396 patients. METHOD: 396 patients with SCCHN were studied. Variables regarding
      the patient, the carcinoma and histology were analysed by multivariate analysis
      using BMDP's PLR programme. RESULTS: Some variables appear to represent
      predisposing factors for tumor spread to the lymph nodes: tumor site
      (supraglottic larynx: P = 0.005; base of the tongue: P = 0.02; hypopharynx: P =
      0.02), grading (P = 0.001), and a number of histological parameters (lower degree
      of histological differentiation: P = 0.001; vascular permeation: P = 0.04;
      perineural invasion: P < 0.05; prevalently plasmocytic infiltrate: P < 0.05).
      CONCLUSION: The identification of cases at risk for metastasis can be improved by
      the assessment of prognostic factors, with a consequent improvement in treatment
      strategies.

PMID- 9526586
TI  - Preoperative evaluation of ferritinemia in primary epithelial ovarian cancer.
AB  - AIMS AND BACKGROUND: High ferritin serum levels have been reported in patients
      suffering from various malignancies. The aim of this study was to evaluate the
      role of ferritinemia in the preoperative diagnosis of ovarian carcinoma. METHODS:
      Between March 1993 and September 1996, 60 patients suffering from ovarian
      carcinoma were surgically treated at our Department. Their ferritin serum levels
      were measured preoperatively by a solid-phase, two-site chemiluminescent
      immunometric assay and compared with those of a group of 60 healthy, age-matched,
      non pregnant controls. RESULTS: The mean serum concentration of ferritin was 54.7
      +/- 7.8 ng/ml (range, 14-135) in healthy controls and 112.3 +/- 21.2 ng/ml
      (range, 9-947) in patients with ovarian carcinoma. The difference was
      statistically significant (P = 0.005, X2 test = 7.951). Serum ferritin was
      elevated preoperatively (cutoff > or = 120 ng/ml) in 18/60 patients with
      malignancy (sensitivity 30%), whereas the CA 125 levels were above the cutoff in
      53/60 patients (sensitivity 88.3%). Only 2/60 women of the control group had
      ferritin titers > 120 ng/ml (specificity 96.7%). The ferritin levels increased
      with advancing disease stage; no significant correlation was found between
      ferritin concentration and neoplastic histology and grading. The mean serum iron
      levels were also measured preoperatively in patients with ovarian carcinoma and
      healthy controls. They were 57.2 +/- 3.8 and 66.3 +/- 2.61 micrograms/dl,
      respectively, and the difference was not significant (P = 0.655, X2 test =
      0.200). CONCLUSIONS: The present study underlines that although ferritin shows an
      elevated specificity, its low sensitivity does not suggest any true usefulness as
      a tumor marker in epithelial ovarian cancer.

PMID- 9526587
TI  - Steroid hormone receptors related to parameters characterizing the biology of
      human breast cancer.
AB  - Steroid hormone receptors are important parameters to characterize breast tumors.
      Thus, it is important to evaluate their relationships with factors such as
      histological type and size of the tumor, axillary lymph node invasion and distant
      spread, age and menopausal status of the patients, and parameters of tumor
      differentiation. The receptor levels observed vary within wide ranges. Therefore,
      statistically significant differences between different groups of parameters are
      seldom found. A significant dependence on receptor levels has been observed only
      for patient age and menopausal status. The parameters clinical stage, tumor size,
      tumor histology, metastatic involvement and histopathologic grading showed no
      statistically significant relation with receptor levels. Nevertheless, a
      relationship exists between all parameters mentioned and the frequency of a
      positive receptor status. Consequently, receptor status can contribute to define
      the biological behavior of the disease in specific groups of patients. In
      individual cases other parameters than the biochemical evidence of steroid
      receptor binding seem to be more important. We found that data derived from DNA
      flow cytometric measurements allowed a better recognition of tumor aggressiveness
      than ER status. In axillary lymph node metastases we usually observed higher
      receptor levels than in primary tumors, but we did not find an age dependency of
      ER levels in these metastases.

PMID- 9526588
TI  - AgNOR counts and their combination with flow cytometric analyses and clinical
      parameters as a prognostic indicator in breast carcinoma.
AB  - Silver binding nucleolar organizer regions (AgNORs) were counted in tissue
      sections and were shown to assist in the distinction between benign and malignant
      breast lesions. The mean AgNOR counts in fibroadenomas were 1.05 +/- 0.85 (n =
      18), in lobular carcinoma 3.55 +/- 0.56 (n = 35), and in intraductal carcinoma
      4.83 +/- 1.20 (n = 45). AgNOR counting may provide information on breast cancer
      prognosis supplementary to that obtained with other methods such as flow
      cytometric analysis. The AgNOR values in carcinomas were also compared with
      ploidy and S-phase fractions (S) by flow cytometry. More than 75% of the total
      cancers with counts above 3 dots per nuclear profile contained aneuploid cells,
      whereas 20% with counts below 3 contained diploid cells (P < 0.05). Similar
      trends were noticed with regard to S-phase fractions, which were 45% +/- 12.5 and
      14% +/- 4.5, respectively, for the two groups (P < 0.05). AgNOR counting, flow
      cytometry and clinical parameters may provide complementary information on breast
      cancer prognosis.

PMID- 9526589
TI  - Serum lipid profile and its relationship with host immunity in carcinomas of the
      breast and uterine cervix.
AB  - Carcinomas of the uterine cervix and breast, which have a different
      etiopathogenesis, are the most common malignancies among Indian women. Between
      these two cancers a comparative study was undertaken in which serum lipids were
      assessed along with host immunity. Thirty randomly selected cases each of breast
      and cervical carcinoma, and 20 matched healthy control women were studied by
      means of standard procedures. Significantly higher (P < 0.001) mean levels of
      triglycerides (x = 192.1 mg/dl, SD +/- 113.5) and total cholesterol (x = 212.9
      mg/dl, SD +/- 49.78) were observed in breast cancer as compared to controls or
      cervical cancer patients. Patients with cervical cancer had low mean values of
      all lipid fractions. Women with the above malignancies also showed a
      significantly decreased CD3+ and CD4+ population (P < 0.001), while there was a
      significant increase in CD8+ cells (P < 0.005) compared to normal controls.
      Interestingly, a significant relationship (P < 0.05) was observed between CD8+
      cells and LDL-cholesterol among the cancer patients (r = 0.3652 and r = 0.4298
      for carcinomas of breast and cervix, respectively.

PMID- 9526590
TI  - Hypercoagulable state in patients with advanced gastrointestinal cancer: evidence
      for an acquired resistance to activated protein C.
AB  - AIMS AND BACKGROUND: Thromboembolic complications are common in patients with
      cancer and represent the second cause of death in patients with overt malignant
      disease. The aim of this study was to investigate the activated protein C pathway
      in cancer. METHODS: We studied the coagulation cascade, natural clotting
      inhibitors, fibrinolytic proteins and resistance to activated protein C in 20
      patients with advanced gastrointestinal cancer and 84 volunteers by measuring PT,
      APTT, fibrinogen, AT III, PC, PS, APC resistance, fibrinolytic system (PLG, ANPL,
      PAI-1, and t-PA) and activation peptides (D-Dimers, prothrombin 0 fragment 1 +
      2/F1 + 2). RESULTS: Laboratory tests confirmed coagulation abnormalities in
      cancer patients. Fibrinogen, D-Dimers and F1 + 2 were increased, while t-PA
      activity was significantly lower than that of controls. APC resistance was higher
      in cancer patients compared to the control group (55% vs 2%; P < 0.0001). Excess
      thrombin generation was manifested by increased F1 + 2 plasma levels in APC
      resistant cancer patients. Genetic analyses showed that only one patient with a
      poor response to APC carried a factor V R506Q mutation in exon 10. CONCLUSIONS:
      Our findings show a high prevalence of APC resistance in cancer, compatible with
      an acquired defect in the APC pathway.

PMID- 9526592
TI  - Cancer of the appendix in long-standing ulcerative colitis: a case report.
AB  - Cancer of the appendix was found in a 69-year-old female patient affected by long
      standing ulcerative colitis (UC). On histological examination the cancer was a
      typical cystadenocarcinoma of the appendix. The appendiceal mucosa not invaded by
      the neoplastic process was normal. Histological examination of the colorectal
      mucosa did not show dysplasia or cancer. These findings suggest that appendiceal
      cancer and UC may be unrelated diseases. A surveillance program for early
      detection of cancer of the appendix in patients with long-standing UC does not
      seem mandatory.

PMID- 9526593
TI  - Epstein-Barr virus and primary lymphoma of the central nervous system in
      immunodeficient patients.

PMID- 9526591
TI  - Antineuronal antibodies in patients with neuroblastoma: relationships with
      clinical features.
AB  - We evaluated the frequency of serum antineuronal antibodies in a cohort of 39
      neuroblastoma patients and related their presence to clinical features. Twelve
      patients displayed antineuronal antibodies at immunocytochemistry. Only one of
      these 12 patients suffered from a clinically overt paraneoplastic syndrome. No
      significant differences emerged between autoantibody-positive and autoantibody
      negative patients in terms of progression-free and overall survival, although
      when only patients evolving to disease progression were considered, the time
      interval between diagnosis and progression was slightly longer in autoantibody
      positive patients.

PMID- 9526594
TI  - New concepts in pharmacokinetics and pharmacodynamics.
AB  - Pharmacokinetic and dynamic drug description aim to optimize drug dosing to a
      desired duration and intensity of effect. In anesthesia practice the therapeutic
      window is narrow and versatile. Rapid adjustments and rapid reversal of drug
      effect are mandatory. The simplified traditional pharmacokinetic parameters lack
      precision to guide dosing and to predict duration of drug effect in routine
      clinical practice and are therefore restrictive for the popularity of intravenous
      anesthesia techniques. The context sensitive half-time is the time required for
      drug concentration to decrease by half of its value after a given drug infusion
      duration. It is a better comparative predictor for drug concentration decay than
      the traditional parameters. Compared to opiates, the context sensitive half-times
      of hypnotics are significantly shorter at any infusion duration. Hysteresis in
      the concentration-affect relationship is responsible for the lag time between
      plasma drug concentration and effect. Hysteresis delays initiation of effect as
      well as recovery from effect. The development of microprocessor aided infusion
      devices will simplify and ameliorate to a significant extend, the sound
      application of intravenous drugs in anesthesia.

PMID- 9526595
TI  - Development of "diprifusor". off.

PMID- 9526596
TI  - Propofol target-controlled infusion in clinical practice.

PMID- 9526597
TI  - Target-controlled anesthesia in neurosurgery. What we are looking at.

PMID- 9526598
TI  - Predictive accuracy of intravenous anesthetic drugs.

PMID- 9526599
TI  - Propofol opioid interaction.

PMID- 9526600
TI  - The development and future of TCI.

PMID- 9526601
TI  - Tenoxicam does not enhance the spread of sensory block produced by intrathecal
      lidocaine.
AB  - Systemic opioids enhance the spread of spinal analgesia. This study was designed
      to determine whether i.v. tenoxicam, a nonsteroidal anti-inflammatory drug
      (NSAID), affects the spread of sensory block produced by lidocaine. Sixty
      patients undergoing transurethral procedures were randomly assigned in a double
      blind design to receive i.v. either 3 ml normal saline (N/S group, n = 20), or
      150 micrograms fentanyl (F group, n = 20), or 40 mg tenoxicam (T group, n = 20),
      20 minutes after spinal anesthesia. The level of sensory loss was tested with
      pinprick sensation 20 minutes after subarachnoid block, but before i.v.
      treatment, and 5, 10, and 15 minutes after i.v. treatment. Five minutes after the
      i.v. treatment the change in the level of sensory block was -0.8 +/- 3.1 cm in
      the N/S group, 4.0 +/- 3.5 cm in the F group and 0.0 +/- 3.9 cm in the T group.
      The changes in the height of sensory block among the three groups differed 5
      minutes and 10 minutes (F = 10.627, df = 2.57, P < 0.001 and F = 4.219, df =
      2.57, P < 0.05 respectively), but not 15 minutes after i.v. treatment. Individual
      comparisons showed a difference between the N/S and F groups (P < 0.01), and
      between the F and T groups (P < 0.01) 5 minutes after treatment, and between the
      N/S and F groups (P < 0.05) 10 minutes after treatment. The overall change in the
      level of sensory block 15 minutes after i.v. treatment was -4.6 +/- 6.3 cm in the
      N/S group, 2.4 +/- 6.0 cm in the F group, and -1.6 +/- 5.8 cm in the T group. The
      F group differed from the N/S group (P < 0.01). Intravenous administration of
      tenoxicam does not enhance the level of spinal analgesia produced by lidocaine.

PMID- 9526602
TI  - Pentylenetetrazol seizure threshold in the rat during recovery phase from
      propofol and thiopentone induced anesthesia.
AB  - Pentylenetetrazol (PTZ) seizure threshold was determined in the rat during
      recovery from anesthesia induced by intravenous administration of propofol (20
      mg/kg) or thiopentone (30 mg/kg). Seizure threshold values determined 10 min
      after the induction of anesthesia by either agents were significantly higher than
      those determined in control animals, indicating an anticonvulsant effect. With
      propofol, the initial rise in PTZ convulsive threshold declined rapidly during
      recovery from anesthesia and returned to control levels 40 min after drug
      administration. With thiopentone, the initial rise in convulsive threshold also
      declined during recovery phase but did not return to control levels at 90 min
      after drug administration. At no time during or after recovery from anesthesia
      induced by either anesthetic agents, did the PTZ conclusive threshold fall below
      control values. Thus, using the PTZ convulsive threshold, no proconvulsant
      effects were detected during the early phase of recovery from propofol or
      thiopentone induced anesthesia.

PMID- 9526603
TI  - Single i.v. bolus dose of ondansetron in the prevention of postoperative nausea
      and emesis.
AB  - In this placebo controlled, double blind multicentre study, the efficacy and
      safety of a single i.v. bolus dose of ondansetron 4 mg were evaluated in the
      prevention of postoperative nausea and vomiting (PONV), which remains one of the
      most unpleasant side effects experienced by patients postoperatively. The study
      population included patients having general anesthesia and undergoing major
      gynecological or elective abdominal surgery by laparoscopy. Thirty three percent
      of placebo-treated patients had at least one emetic episode over 24 hrs compared
      with 21% in the ondansetron group (p = 0.03). Forty two percent of placebo
      treated patients experienced nausea in the 24 hours post-recovery period,
      compared to 27% of patients treated with ondansetron 4 mg (p = 0.01). Several
      factors appeared to be associated with an increased risk of developing PONV,
      namely gender (female), type of surgery (gynecological), experience of previous
      PONV and duration of anesthesia; the use of propofol was not a significant
      factor. Ondansetron was well tolerated, with no side effect being reported as a
      significant problem.

PMID- 9526604
TI  - High levels of anticardiolipin antibodies in patients with abnormal embryo
      morphology who attended an in vitro fertilization program.
AB  - PROBLEM: Recently, it has been suggested that anticardiolipin antibodies (ACAs)
      may serve as possible markers for reproductive failure. The association between
      ACAs and embryo morphology in patients undergoing in vitro fertilization (IVF)
      was investigated. METHOD OF STUDY: This prospective study comprised 117 patients
      with either tubal factor or unexplained infertility. Embryo morphology was
      blindly scored from I to IV according to blastomere regularity and the presence
      of fragments. Anticardiolipin antibodies (immunoglobulin [Ig] G and IgM) were
      detected. RESULTS: Anticardiolipin antibodies were found in 26 (50%) of the 52
      patients with abnormal morphology, compared with 13 (20%) of the 65 patients with
      normal embryo morphology (P = 0.001). No statistically significant differences
      were found between the prevalence of ACAs among patients with tubal factor and
      those with unexplained infertility (29.6% and 36.5%, respectively). CONCLUSIONS:
      Our study shows an association between embryo morphology and the presence of
      ACAs. This association may explain the low implantation rate and early pregnancy
      loss in patients with ACAs.

PMID- 9526605
TI  - Assessment of progesterone-induced acrosome reaction by biotinylated monoclonal
      antibody probes.
AB  - PROBLEM: To develop an immunohistochemical assay for determination of acrosome
      reacted human sperm and to study the effects of progesterone and cholesterol
      treatment on human sperm acrosome reaction. METHOD OF STUDY: Three distinct anti
      sperm monoclonal antibodies were biotinylated and used as probes for assessment
      of acrosome reaction in a 30-min immunohistochemical assay. Progesterone and/or
      cholesterol were added to sperm preparation to influence the acrosome reaction in
      different experimental conditions. RESULTS: Percentages of acrosome-intact sperm
      decreased significantly during the 18-hr incubation. Acrosome reaction could be
      induced by progesterone as early as 2 hr after sperm incubation in human tubal
      fluid. The degree of progesterone-induced acrosome reaction was time dependent
      and the optimal effect was reached by adding 10 micrograms/ml progesterone for 30
      min incubation. Progesterone-induced acrosome reaction was shown to be hormone
      concentration dependent with 50% stimulation at 1 microgram/ml. Cholesterol (1
      microgram/ml) was found to inhibit progesterone-induced acrosome reaction either
      by co-incubation with human sperm during capacitation, or by simultaneous
      incubation with progesterone during acrosome reaction induction. CONCLUSIONS:
      Assessment of human sperm acrosomal status by avidin-biotin immunohistochemical
      assay can be a routine in clinical laboratories for male infertility services.
      Cholesterol can inhibit progesterone-induced acrosome reaction, possibly by its
      modifications of sperm plasma membrane and/or interference of progesterone
      binding to its surface receptors.

PMID- 9526607
TI  - Soluble intercellular adhesion molecule-1 serum profile in physiologic and
      preeclamptic pregnancy.
AB  - PROBLEM: The aim of this study was to determine serum levels of soluble
      intercellular adhesion molecule (sICAM)-1, an adhesion receptor that mediates
      interactions with the immune system, in physiologic and preeclamptic pregnancies.
      Moreover, we evaluated whether the release of sICAM-1 during pregnancy correlated
      to plasma fibronectin concentrations. METHOD OF STUDY: Serum was collected from
      18 nonpregnant, control women, from 58 normal pregnant women during the first (n
      = 13), second (n = 15), and third (n = 30) trimesters, and from 25 preeclamptic
      patients at 27-39 weeks' gestation. All samples were assayed for sICAM-1 by a
      specific enzyme-linked immunoassay and for fibronectin by a nephelometric system.
      Serum sICAM-1 levels in preeclamptic patients were compared to those obtained
      from gestational-matched normal pregnant women. RESULTS: Levels of sICAM-1 were
      significantly elevated (P < 0.001) in each of the three trimesters of normal
      pregnancy (I trimester: 390.4 +/- 25.7 ng/ml; II trimester: 386.3 +/- 15.4 ng/ml;
      and III trimester: 367.3 +/- 15.8 ng/ml) when compared to those of healthy
      nonpregnant women (263.3 +/- 11.6 ng/ml). No significant difference in sICAM-1
      concentrations was observed among the three trimesters. Preeclampsia was
      associated to a significant decrease (P < 0.01) of sICAM-1 levels (309.8 +/- 11.6
      ng/ml) relative to those observed in gestational-matched pregnant women (367.3 +/
      15.8 ng/ml). Fibronectin and sICAM-1 levels did not correlate. CONCLUSION: The
      increased levels of sICAM-1 found in physiologic pregnancies and its reduction in
      preeclampsia may account for some of the immunologic alterations demonstrated to
      be associated with pregnancy.

PMID- 9526606
TI  - Preliminary studies with recombinant chorionic gonadotropin beta-subunit produced
      in Escherichia coli for use as an antigen in a birth control vaccine.
AB  - PROBLEM: Prototype human chorionic gonadotropin (hCG) vaccines based on natural
      sources are unsuitable for widespread applications due to their complex
      manufacturing procedures, cost, and carrier-mediated immune suppression. METHOD
      OF STUDY: Wistar rats were immunized with alum-adsorbed CG beta (recombinant), CG
      beta-TT, and nCG beta (native CG beta)-TT, whereas Bonnet monkeys were immunized
      with only CG beta. The anti-hCG antibody titre in the sera obtained at different
      time points were quantified by radioimmunoassay. The sera of Wistar rats were
      characterized in terms of their affinity to hCG, bioneutralization capacity (by
      inhibition of hCG-induced testosterone production in Leydig cells), and cross
      reactivity with human luteinizing hormone, human follicle-stimulating hormone,
      and human thyroid-stimulating hormone (by direct binding assays). RESULTS:
      Antigen-binding capacities of sera obtained upon immunization with CG beta were
      3,080 +/- 943 ng/ml (n = 6) and 3,993 +/- 1,292 ng/ml (n = 4), respectively, in
      rats and monkeys. The analysis of data revealed that immunization of rats with CG
      beta produced antibodies comparable to that of CG beta-TT and nCG beta-TT.
      CONCLUSION: The study opens up the possibility of producing pure and highly
      immunogenic CG beta by a recombinant DNA route, as a consistent source of antigen
      for birth control vaccine.

PMID- 9526608
TI  - Female reproductive tract immunity in bovine trichomoniasis.
AB  - PROBLEM: Mechanisms of protective immunity in the female reproductive tract are
      poorly understood. For sexually transmitted diseases, bovine trichomoniasis is a
      useful model because it resembles human trichomoniasis to some extent, and
      antibodies play an important role in protection against these extracellular
      parasites. Protective efficacy was compared in animals with genital responses of
      predominantly immunoglobulin G (IgG) or predominantly IgA antibodies to a
      purified surface antigen of Tritrichomonas foetus. METHOD OF STUDY: Immunization
      of mice by various routes with immunoaffinity-purified T. foetus surface antigen
      (TF1.17) or killed cells was used to define the best routes and antigen
      combinations to give predominantly IgG or IgA antibodies to TF1.17 antigens in
      genital secretions. Cattle were then immunized either subcutaneously (SC) two
      times with TF1.17 antigen and once SC with killed T. foetus or twice SC with
      TF1.17 antigen and once intravaginally with killed T. foetus. All immunizations
      were in Quil A adjuvant. Controls were not immunized. Animals were challenged
      intravaginally with 10(6) T. foetus 3 weeks after the third immunization. Vaginal
      mucus was collected weekly for culture and antibody assays. Serum was collected
      weekly, and uterine secretions were collected at 10 weeks post-challenge. Tissues
      were fixed at 10 weeks also. RESULTS: Murine studies showed systemic priming with
      vaginal boosting gave the highest genital IgA responses. In cattle, systemic
      immunization (group S) induced high IgG1 antibody levels in vaginal secretions.
      Systemic priming with vaginal boosting (group S/V) primed for an anamnestic
      vaginal IgA response after challenge with T. foetus. Cattle with predominantly
      IgG or predominantly IgA responses in vaginal secretions either did not become
      infected or cleared infection faster than controls. Uterine IgA responses at 10
      weeks were highest in the vaginally boosted group, but other responses were not
      different from the controls at this time point. Microscopic examination of
      genital tissues showed subepithelial infiltration of mononuclear cells in all
      groups. Lymphoid aggregates or nodules were detected in vaginal sections in
      cattle of groups S/V and C as well as in uterine sections of all animals in all
      three groups. CONCLUSIONS: Both IgG and IgA antibodies to T. foetus superficial
      antigen were associated with protection. The timing of the response was related
      to the time of clearance. Lymphoid organization in the vagina and uterine tissues
      suggested development of mucosal inductive sites.

PMID- 9526609
TI  - Vaginal immunization with recombinant gram-positive bacteria.
AB  - PROBLEM: Many viral and bacterial pathogens enter the body through the genital
      mucosa. Therefore, one of the major goals of a vaccine against sexually
      transmitted diseases (STDs) should be to induce an immune response in the genital
      mucosa capable of controlling the entry of the pathogen. Our approach for the
      development of vaccines against STDs is based on the use of nonpathogenic Gram
      positive bacteria as live vaccine vectors. METHOD OF STUDY: Recombinant Gram
      positive bacteria expressing vaccine antigens were constructed using genetic
      systems developed in our laboratory. Balb/c mice and Cynomolgus monkeys were
      inoculated by the vaginal route and vaginal samples were collected using
      absorbent wicks. Colonization was evaluated by the presence of recombinant
      bacteria in the vaginal samples. Local and systemic immune responses were
      studied. RESULTS: We have developed genetic systems for the expression of
      heterologous antigens on the surface of the human commensals Streptococcus
      gordonii and Lactobacillus spp. Both S. gordonii and L. casei stably colonized
      the murine vagina after a single inoculum. Vaginal colonization of mice with
      recombinant strains of S. gordonii, expressing human papillomavirus (HPV) and
      human immunodeficiency virus (HIV) antigens, induced antigen-specific vaginal
      immunoglobulin A (IgA) and serum IgG. Local and systemic immune responses also
      were detected in monkeys immunized intravaginally with recombinant S. gordonii.
      CONCLUSION: The results obtained indicated that the approach of using colonizing
      Gram-positive bacteria as live vectors has a great potential for the development
      of vaccines against STDs.

PMID- 9526610
TI  - Influence of the estrous cycle on the presence and distribution of immune cells
      in the rat reproductive tract.
AB  - PROBLEM: Previous studies have shown that the uterus and vagina contain cells
      that can present antigen to ovalbumin-specific T-cells. The objective of the
      present study was to systematically characterize the immune cells [major
      histocompatibility complex (MHC) class-II+, macrophages, granulocytes, dendritic
      cells, and CD8+ cells] present in the uterus and vagina of the rat and to examine
      their distribution at various stages of the estrous cycle. METHOD OF STUDY:
      Uterine and vaginal tissues from female rats were selected at various stages of
      the estrous cycle and were examined by immunohistochemical analysis. MHC class-II
      (Ia)-positive cells were detected using the OX-6 monoclonal antibody;
      macrophages, granulocytes, and dendritic cells were detected by OX-41 monoclonal
      antibody and CD8-positive T-cells were identified by OX-8 monoclonal antibody.
      RESULTS: Immunohistochemical analysis showed cycle-dependent changes in the
      immune cell populations in the uterus and vagina. Ia+ cells, macrophages,
      granulocytes, and dendritic cells were present in large numbers in the stroma of
      the endometrium and around the glandular epithelium in the uterus at estrus, the
      stage of the reproductive cycle when estradiol levels are known to be high,
      relative to those seen at diestrus, when estrogen levels are low and progesterone
      is the predominant hormone. CD8+ cells were observed in the uterus interspersed
      between glandular epithelial cells at estrus. Immune cells were more numerous in
      the vagina, relative to the uterus. OX-6 and OX-41-positive cells were present in
      greater numbers in the subepithelial layers of the vagina at diestrus, in
      contrast to estrus. CONCLUSION: This study demonstrates that a variety of immune
      cells are present in the reproductive tract and that their number and
      distribution vary in a tissue-specific manner with the stage of the estrous
      cycle.

PMID- 9526611
TI  - Evidence that folliculo-stellate cells mediate the inhibitory effect of Japanese
      kampo medicine, unkei-to, on growth hormone secretion in rat anterior pituitary
      cell cultures.
AB  - PROBLEM: Cytokine-induced neutrophil chemoattractant (CINC) was reported to
      influence anterior pituitary hormone release. We recently found that Unkei-to,
      one of the Japanese Kampo medicines, stimulated CINC secretion by rat anterior
      pituitary cells and the pituitary folliculo-stellate (FS)-like cell line
      (TtT/GF). Therefore, the effect of Unkei-to on growth hormone (GH) secretion by
      rat anterior pituitary cells was investigated. METHOD OF STUDY: Dispersed normal
      anterior pituitary cells, the folliculo-stellate-like cell line TtT/GF, and the
      GH3 cell were used to test the effect of Unkei-to on GH secretion. In
      reconstitutive coculture experiments, TtT/GF cells were mixed with GH3 cells at a
      ratio (TtT/GF cells: GH3 cells) of 1:99. From this mixture, cells were seeded
      onto plates at a density of 10(4) cells/well and were cultured for 5 days. The
      cells were then used in the experiments. RESULTS: Unkei-to at 20 micrograms/ml
      significantly inhibited GH secretion by normal anterior pituitary cells within 12
      hr of incubation. In contrast Unkei-to stimulated GH secretion by GH3 cells in a
      time- and dose-dependent manner, suggesting that an accessory cell type was
      involved. To assess the contribution of CINC as a paracrine factor, an experiment
      using a reconstitutive coculture system was performed, and Unkei-to was found to
      inhibit GH secretion when GH3 cells were cocultured with TtT/GF cells. The
      addition of anti-CINC antibody to the reconstitutive coculture system antagonized
      Unkei-to-inhibited GH secretion. CONCLUSION: CINC, which was secreted from FS
      cells by Unkei-to, may be responsible for mediating the inhibitory effect of
      Unkei-to on GH secretion by rat anterior pituitary cells.

PMID- 9526612
TI  - Risk factors in congenital anal atresias.
AB  - Congenital anal atresias were studied in a small geographical area in 225,752
      consecutive births. For each of the 108 new cases studied during the period 1979
      to 1995, more than 50 factors were compared in probands and in controls. The
      prevalence rate of congenital anal atresias was 4.8 per 10,000 births. Sex ratio
      was 0.96. Prenatal diagnosis was performed in 14 cases and 11 cases were induced
      abortions. The more common types of associated malformations in the 45 non
      syndromic affected cases with at least one major anomaly other than anal atresia
      were renal agenesia, genital anomalies and ventricular septal defect. At births
      infants with anal atresia and other malformations were smaller, weighted less and
      their head circumference was lower than in controls. Placental weight was also
      lower than in controls. Pregnancies with anal atresia were more often complicated
      by threatened abortion, oligoamnios and polyhydramnios. Mothers of children with
      congenital anal atresia took more often drugs during pregnancy than mothers of
      controls. Fathers of children with anal atresia were more often exposed to
      occupational hazards than fathers of controls. There was a significant
      association between anal atresia and consanguinity of parents (p < 0.05). The
      recurrence risk for first degree relatives of probands was 3.7%. First degree
      relatives of probands had more than twice the prevalence of non-anal atresia
      malformations than controls.

PMID- 9526613
TI  - Clinical features of cystic fibrosis patients with rare genotypes in Saguenay Lac
      Saint-Jean (Quebec, Canada).
AB  - We describe the clinical features of six cystic fibrosis (CF) patients from
      Saguenay Lac-Saint-Jean who bear rare genotypes. Two patients with a delta
      F508/I148T genotype had pancreatic insufficiency, as did two patients compound
      heterozygous for the 621 + 1G-->T mutation who also had a major growth
      retardation. One CF adult who carried a delta F508/Q890X genotype had meconium
      ileus and bronchiectasis. The sixth patient (A455E/R117C) had borderline sweat
      chloride concentrations; the diagnosis of cystic fibrosis had remained doubtful
      until the molecular analysis showed the presence of two CF mutations. The seventh
      patient with a delta F508/R1158X genotype experienced several complications and
      is now 43 years old.

PMID- 9526614
TI  - Tandem duplication of chromosome 14 (q12q13).
AB  - A nine-years-old Egyptian boy was referred for speech and language delay. He has
      an I.Q. of 35 which is in the moderately to severely delayed range. Routine
      cytogenetic and FISH-techniques revealed a de novo tandem duplication of
      chromosome 14 bands q12 and q13, i.e., 46, XY, dup (14)(q12q13) and there are no
      investigations reporting a direct de novo duplication for this region.

PMID- 9526615
TI  - PEG1 expression in maternal uniparental disomy 7.
AB  - PAG1/MEST is an imprinted gene mapping to human chromosome 7q32. In human embryos
      and placenta, PEG1 is expressed from the paternally derived allele only, while
      maternal and paternal alleles are transcribed in adult blood lymphocytes. We
      aimed at investigating the origin of the maternal PEG1 transcript by studying
      PEG1 mRNA in two maternal uniparental disomy 7 patients suffering from severe pre
      and post-natal growth restriction. PEG1 expression has been characterised by RT
      PCR from leukocytes RNA using several primer pairs. The distal coding region in
      PEG1 mRNA could be repeatedly amplified from mUPD patients blood cells, but no
      amplification could be performed from the first exon, suggesting that the first
      exon was not a component of the maternal PEG1 transcript. As six independent
      database sequences showed that exon 2 was exactly joined to a novel sequence
      unrelated to exon 1 but identical in the common region of the six sequences, we
      hypothesized that our observation of PEG1 expression in the two maternal
      uniparental disomy 7 patients could be explained by transcription of the maternal
      allele from an alternate maternal upstream promoter.

PMID- 9526616
TI  - De novo trisomy 22 due to an extra 22Q-chromosome.
AB  - Trisomy 22 is the most frequent trisomy, after trisomy 16, of the trisomies
      present in miscarriages. The children born with trisomy 22 have usually
      unbalanced translocations 11; 22 or mosaicisms. In a recent review Bacino et al.
      [1] were able to find 17 cases of children born with trisomy 22 including only 3
      cases confirmed by molecular cytogenetics. We report a patient with an extra
      chromosome 22q- without mosaicism. This chromosomal anomaly was defined with FISH
      studies. The phenotype include microcephaly, microtia with pre auricular tags,
      hypertelorism, epicanthus, palatal cleft, short neck, winging scapulae,
      hypoplasia of the distal phalanges, pulmonary stenosis and mental retardation.

PMID- 9526617
TI  - Homozygosity for pericentric inversions of chromosome 9. Prenatal diagnosis of
      two cases.
AB  - The finding of homozygosity for a pericentric inversion of chromosome 9 [inv(9)]
      is rare, and previously has not been reported at prenatal diagnosis. We describe
      two unrelated cases of homozygosity for inv(9) identified in amniocytes. In each
      case, both parents were heterozygotes for the inv(9); 46,XX,inv(9)(p11q13) and
      46,XY,inv(9) (p11q13). Case 1 resulted in a normal term infant who at age 5 years
      was phenotypically and developmentally normal. Case 2 was referred for severe
      intrauterine growth retardation (IUGR) and oligohydramnios, and subsequently
      expired in utero. Even though inv(9) is a normal chromosome variant with a
      frequency of 1 to 3% in the general population, the finding of homozygosity for
      inv(9) and IUGR in this fetus suggested the possibility of uniparental disomy
      (UPD). Molecular studies confirmed the presence of both parental inv(9)
      chromosomes, excluding the possibility of chromosome 9 UPD as the cause of IUGR
      in this fetus. Presumably, inv(9) homozygosity results from the high frequency of
      inv(9) heterozygosity, and is a normal variant. However, until the effects of UPD
      for chromosome 9 are established, parental karyo types and, where appropriate,
      molecular studies should be performed to exclude UPD. In addition, more reports
      of inv(9) homozygosity detected prenatally are needed to assess its frequency and
      outcome.

PMID- 9526618
TI  - Assignment of ferritin L gene (FTL) to human chromosome band 19q13.3 by in situ
      hybridization.
AB  - A new genetic disorder (Hyperferritinemia and Cataract Syndrome) characterized by
      a combination of high serum ferritin level and congenital bilateral nuclear
      cataract has been recently described. This disease is transmitted as autosomal
      dominant trait and is due to mutations in the ferritin L gene (FTL). FTL gene has
      been localized to 19q13.3-qter by somatic cell hybrids. In this work we present
      the precise mapping of FTL gene on chromosome 19q13.3 using in situ fluorescence
      hybridization.

PMID- 9526619
TI  - An unusual G-negative band within 1qh region a rare variant or an abnormality?
AB  - Morphological variations due to heterochromatic DNA of the secondary constriction
      region (qh) of human chromosome 1 are considered normal. The structural
      abnormalities involving or in association within the qh region have been
      difficult to characterize by routine cytogenetic methods and in turn have often
      gone undetected. In the past, the presence of a G-negative band within the qh
      region of chromosome 9 has been considered as a rare or unusual variant.
      Fortuitously, we were referred two cases where a G-negative band was embedded
      within the secondary constriction region of chromosome 1. Whole chromosome #1
      specific painting probe, did hybridize to the band. Both patients have speech
      delay. Unfortunately, the parents were not available to confirm the mode of
      inheritance, nor could a definite conclusion be reached concerning its morbidity.
      Nevertheless, we are tempted to hypothesize that this is an unusual variant where
      a G-negative band apparently became genetically inert when it was sandwiched
      between two blocks of heterochromatin. Similar to a rare variant of chromosome 9
      it could be found in the qh region of chromosome 16 as well, whose clinical
      consequences remain obscure.

PMID- 9526620
TI  - Identical chromosome imbalance in two siblings born to a mother with a double
      reciprocal translocation.
AB  - We report the case of a woman who carried two reciprocal translocations. Her
      karyotype was 46,XX,t(3;12)(q12;q21)(4;17)(p14;p13). She had two children, a
      phenotypically normal daughter (karyotype (46,XX,t(3;12)(q12;q21)) and a son with
      partial 4p trisomy (karyotype 46,XY,t(3;12) (q12;q21),-17,+maternal der(17)). She
      was pregnant with a female fetus who had the same karyotype as her son. She also
      reported a history of two spontaneous abortions. This viable recurrent
      abnormality was due to the maternal (4;17) translocation with meiotic segregation
      type 2:2 adjacent 1. In this case of the two reciprocal translocations carried by
      the mother, one led to imbalances, whereas the other remained balanced in the
      viable offspring.

PMID- 9526621
TI  - Trisomy 18 mosaicism in a mildly retarded boy with postnatal overgrowth.
AB  - We report a 6-year-old mildly retarded boy with trisomy 18 in 44% of peripheral
      lymphocytes. He had mild nonspecific dysmorphic features, microcephaly,
      micropenis with cryptorchidism and postnatal overgrowth. Trisomy 18 mosaicism was
      confirmed by a fluorescent in situ hybridization study. Ten previous reports of
      trisomy 18 mosaicism with normal or subnormal intelligence have been described
      but only one case of trisomy 18 mosaicism with high stature has been reported.

PMID- 9526622
TI  - [Prognostic factors in soft tissue sarcoma in the adult].

PMID- 9526623
TI  - [Chronic intestinal pseudo-obstruction syndrome in the child. Histologic
      classification].

PMID- 9526624
TI  - [Intestinal innervation].

PMID- 9526625
TI  - [Sarcomatoid variant of chromophobe renal cell carcinoma. Report of 2 cases].
AB  - In this paper, we report two cases of sarcomatoid carcinoma arising in
      chromophobe carcinoma. The sarcomatoid component appeared as white, shiny areas,
      occupying less than 10% of each tumor and containing numerous mitotic figures.
      Whereas both components expressed cytokeratin, only the carcinomatous cells were
      positive for epithelial membrane antigen and only the sarcomatoid cells were
      found to express vimentine. Sarcomatoid transformation in chromophobe cell
      carcinoma has been reported exceptionally. An aggressive behavior may be
      expected. The variable proportion of sarcomatoid component may lead to
      multiplication of the samples, especially when white, firm and shiny areas are
      detected on gross findings.

PMID- 9526626
TI  - [Clear cell sarcoma of the kidney in a young adult].
AB  - We report a case of clear cell sarcoma of kidney (CCSK), in a young adult. This
      highly malignant renal tumor usually arises in children of one or two year old
      and represents 4% of renal tumors. The aggressivity of this tumor and its
      affinity to give bone metastasis imply to recognize it in order to institute
      appropriate chemotherapy.

PMID- 9526627
TI  - [Clear cell sarcoma of the kidney relapsing after 10 years of asymptomatic
      evolution].
AB  - We report the case of a kidney tumor occurring in a thirteen year-old girl. This
      tumor was first diagnosed and treated as a benign one. After ten years without
      recurrence, a relapse occurred. The diagnosis was recurrent clear cell sarcoma of
      the kidney. The course in our case is uncommon because clear cell sarcoma of the
      kidney is a rare and aggressive pediatric neoplasm, usually characterized by a
      predilection for bone metastases, and a mid survival rate of 30 months without
      treatment.

PMID- 9526628
TI  - [An exceptional variety of medulloblastoma: melanotic medulloblastoma].
AB  - We report a new case of melanotic medulloblastoma of the vermis in a 3 1/2 year
      old boy. This tumor showed a typical histological appearance with
      pseudoepithelial pigmented structures immunoreactive for S100 protein and
      vimentin. The tumor did not recur after total surgical removal and post operative
      radiation. However, after a 10 year follow-up, imaging demonstrated that a second
      tumor occurred in the left cerebellar hemisphere, which, on histological
      examination, was a typical glioblastoma. Hypothesis concerning the histogenesis
      of the second tumor, as well as a causal association with radiation therapy and
      possible contribution of growth hormone therapy are discussed.

PMID- 9526629
TI  - [Mesenteric lipoblastoma with changes in chromosome 8: use of cytogenetics in the
      diagnosis of adipocytic tumors in children].
AB  - Lipoblastoma is a rare type of benign tumor occurring in infants. We report a
      case of mesenteric lipoblastoma with histologic, electron microscopic and
      cytogenetic studies. The microscopic features of this tumor including lipoblastic
      proliferation and prominent immature capillary beds were typical of lipoblastoma.
      Cytogenetic study showed a karyotype 46,XX, inv (8) (p 21.1; q 24.2). We discuss
      the usefulness of cytogenetic study associated to fluorescent in situ
      hybridization, in the diagnosis of the lipoblastic tumors, i.e. myoxoid
      liposarcoma and lipoblastoma.

PMID- 9526630
TI  - [Extra-cardiac rhabdomyoma of the fetal type].
AB  - Rhabdomyomas are benign tumors of striated muscle. They are distinguished by
      topographic data: cardiac or genital and by histological criteria: foetal or
      adult type. The foetal type is the most heterogeneous, with either a majority of
      immature cells or a mixture of maturing elements. This diversity has led to
      distinguish immature (or standard) foetal Rhabdomyomas from intermediate foetal
      Rhabdomyomas. One observation of this last type is reported. The authors
      highlight the essential characteristics of foetal Rhabdomyomas, however the exact
      meaning remains unclear: an anomaly in the differentiation of the striated
      muscle? or a true tumoral process through genetic anomaly?

PMID- 9526631
TI  - [Thyroid paraganglioma: report of a case].
AB  - A case of thyroid gland paraganglioma is reported in a 48-year-old woman with
      cold thyroid nodule. Review of the literature reveals only 4 cases of
      intrathyroidal paraganglioma but none of them have complete immunohistochemical
      study. The main differential diagnosis in this localization, namely medullary
      carcinoma and trabecular hyalinizing adenoma, are discussed.

PMID- 9526632
TI  - [An unusual urothelial tumor].

PMID- 9526633
TI  - [An unusual inflammatory granuloma of the skin].

PMID- 9526634
TI  - [Diagnosis of a thyroid nodule].

PMID- 9526635
TI  - Low-voltage separation of phosphoamino acids by silica gel thin-layer
      electrophoresis in a DNA electrophoresis cell.

PMID- 9526636
TI  - In situ detection method for glutaminyl cyclase activity in polyacrylamide gels.

PMID- 9526637
TI  - Analysis of cell-cycle profiles in transfected cells using a membrane-targeted
      GFP.

PMID- 9526638
TI  - Chemiluminescence-based detection of minute amounts of apoptotic DNA.

PMID- 9526639
TI  - Rapid screening of fusion protein recombinants by measuring effects of protein
      overexpression on cell growth.

PMID- 9526640
TI  - Versatile low-copy-number plasmids for temperature-inducible overexpression of
      bacterial genes in Escherichia coli.

PMID- 9526641
TI  - Chemiluminescence-based RNase protection assays for simultaneous quantification
      of procollagen mRNAs containing AU-rich regions.

PMID- 9526642
TI  - Modification of primer design facilitates the use of differential display.

PMID- 9526643
TI  - Use of novel downstream primers for differential display RT-PCR.

PMID- 9526644
TI  - Rapid cloning of telomere-associated sequence using primer-tagged amplification.

PMID- 9526645
TI  - PCR-assisted cDNA cloning: a guided tour of the minefield.

PMID- 9526646
TI  - Use of the restriction enzyme AvaI and exo- Bst polymerase in strand displacement
      amplification.

PMID- 9526647
TI  - Long-distance genome walking using the long and accurate polymerase chain
      reaction.

PMID- 9526648
TI  - Relative amplification efficiency of differently sized templates by long-distance
      PCR.

PMID- 9526649
TI  - Re-amplification of short primer-generated bands from RAPD and methylation
      sensitive restriction fingerprinting by discrimination primers.

PMID- 9526650
TI  - Direct amplification of microsatellite alleles from sonicated goldfish sperm.

PMID- 9526651
TI  - Construction of a device composed of common plumbing supplies for freezing
      microscopy samples.

PMID- 9526652
TI  - Simultaneous purification of RNA and DNA from liver using sodium acetate
      precipitation.

PMID- 9526653
TI  - Random mutagenesis by whole-plasmid PCR amplification.
AB  - Random mutagenesis has become a powerful means of studying the effects of a large
      number of permutations of a particular DNA sequence. As a prime example,
      libraries of randomized cDNA clones, when translated into their corresponding
      proteins, can be useful in investigating the functional contributions of a
      mutagenized region to the overall properties of a protein. Existing molecular
      cloning techniques for random mutagenesis are tedious and frequently plagued with
      high levels of background from wild-type (nonmutagenized) template. We report a
      PCR-based method involving amplification of an entire plasmid containing a gene
      sequence of interest with partially complementary degenerate oligonucleotides for
      randomization of up to 12 consecutive nucleotide residues. Sequential treatment
      of the PCR product with Dpn/and a second specific restriction endonuclease and T4
      DNA ligase followed by high-efficiency electroporation permits the generation of
      libraries with very low background. This technique should prove useful for
      studies on enzyme structure-function relationships as well as for other diverse
      applications.

PMID- 9526654
TI  - Long PCRs of transposons in the structural analysis of genes encoding acquired
      glycopeptide resistance in enterococci.
AB  - Glycopeptide-resistant enterococci (GRE) associated with multiple antibiotic
      resistance present a major challenge to clinical practice and infection control
      due to limited or nonexistent antimicrobial treatment options. The genes encoding
      VanA- and VanB-type glycopeptide resistance have been shown to reside on
      transposons Tn1546 and Tn1547, respectively. These transferable genetic elements
      may carry the resistance determinants between and within different ecological
      niches. Molecular epidemiological studies of nosocomial outbreaks of VanA- and
      VanB-type GRE indicate horizontal transfer of glycopeptide resistance genes as an
      important mechanism for the spread of GRE. To target infection control and better
      understand the epidemiology of GRE, outbreak investigations and molecular
      epidemiological studies should therefore apply at least two different approaches,
      i.e., molecular-typing methods to analyze bacterial genomic heterogeneity and
      structural analysis of mobile resistance determinants. Here we describe the
      development and use of long PCRs in the structural analysis of vanA and vanB gene
      clusters in GRE.

PMID- 9526655
TI  - Bacterial growth medium that significantly increases the yield of recombinant
      plasmid.
AB  - Isolation of plasmid DNA from Escherichia coli is a daily activity in many
      molecular biology laboratories. A number of protocols and media recipes have been
      reported in an effort to make this process more efficient. Here we describe a
      growth medium that supports much higher E. coli cell densities and,
      concomitantly, a much higher yield of plasmid than previously reported for small
      scale applications. On a unit volume basis, E. coli cultures grown in this
      medium, termed H15, produce up to 30-fold more recombinant plasmid than in
      conventional rich media, paralleling the increase in cell density. This
      phenomenon is independent of E. coli host strain, DNA insert size and plasmid
      copy number. H15 medium is also very economical; as much as 6 mg of plasmid can
      be harvested per dollar of medium.

PMID- 9526656
TI  - 5'-degenerate 3'-dideoxy-terminated competitors of PCR primers increase
      specificity of amplification.
AB  - Amplification of a product in PCR with specific primers may be viewed as an
      artificial Darwinian-type "selection of the fittest". In other selective systems,
      such as general evolution, immune system and probably brain cortex, the
      stringency of selection is not absolute but rather degenerate, with selection of
      many highly fit units, not limited, however, to only the fittest. In PCR also,
      annealing of the primers is not absolutely specific. The subsequent amplification
      frequently leads to amplification of not only the desired product but also to
      less-specific sequences. Using theoretical analysis of the degenerate mode of
      selection, we predict theoretically and prove experimentally that 5'-degenerate,
      3'-dideoxy-terminated competitors of PCR primers can be used to dramatically
      improve the specificity of PCR amplification without affecting the quantitation
      of the final specific product.

PMID- 9526657
TI  - Small-scale isolation of genomic DNA from Streptomyces mycelia or spores.
AB  - We have developed a small-scale method for isolating high-quality chromosomal DNA
      from Streptomyces species. The entire procedure may be carried out in 2-mL
      microcentrifuge tubes in one day. It has been tested both quantitatively and
      qualitatively to ensure reliability and reproducibility. DNA yields from a
      variety of Streptomyces species ranged from 30 micrograms DNA/50 mg cells to over
      225 micrograms DNA/50 mg cells. We used the method to isolate DNA from cells
      grown in liquid culture, on solid media and from spore suspensions. DNA yields
      and quality were assessed by spectrophotometry, restriction endonuclease
      digestion and random-amplified polymorphic DNA-PCR (RAPD-PCR) analysis. These
      confirmed that this procedure is an efficient method for isolating large amounts
      of high-quality DNA from a wide range of Streptomyces species.

PMID- 9526658
TI  - Simultaneous detection of two GFP spectral mutants during in vivo confocal
      microscopy of migrating Dictyostelium cells.
AB  - A method is described that allows simultaneous measurement of two spectrally
      distinguishable green fluorescent protein (GFP) mutants with a confocal
      microscope. In contrast to previously described methods, neither UV excitation
      nor repetition of scans is required. Therefore the method is well-suited to the
      long-time observation of living cells in three-dimensional microscopy and time
      series recording, as demonstrated with GFP-expressing Dictyostelium discoideum
      cells.

PMID- 9526659
TI  - Development and applications of enhanced green fluorescent protein mutants.
AB  - The introduction of several mutations resulted in the generation of improved
      mutants of the green fluorescent protein (GFP). A strong green (GFPsg25) and blue
      (BFPsg50) fluorescent protein, gave 50-fold-100-fold brighter fluorescence
      compared to wild-type GFP and BFP (Tyr66His), respectively, upon expression in
      mammalian cells. GFPsg25 and BFPsg50 have different excitation and emission
      maxima. This allows their use as an efficient dual-color tagging system and their
      independent detection in living cells.

PMID- 9526660
TI  - Localization of trinucleotide repeat sequences in myotonic dystrophy cells using
      a single fluorochrome-labeled PNA probe.
AB  - A labeled peptide nucleic acid (PNA) antisense probe was used to study the
      spatial distribution of triplet repeats (CTG) in human myotonic dystrophy (DM)
      cells by high-resolution fluorescence in situ hybridization (FISH). It was found
      that transcripts containing triplet repeats were present as a number of discrete
      foci in the DM nuclei. Greater numbers of foci were visible with the PNA probe
      than a comparable DNA probe. The PNA probe was also used to visualize the triplet
      repeat expansion within the DM gene located on chromosome 19. Using the intensity
      of the expanded triplet-repeat on the chromosomes as a reference, it was
      estimated there were between 15-230 RNA molecules in each focus observed in DM
      nuclei.

PMID- 9526661
TI  - Fusion of green fluorescent protein with the Zeocin-resistance marker allows
      visual screening and drug selection of transfected eukaryotic cells.
AB  - Green fluorescent protein (GFP) and the Zeocin-resistance gene Sh ble (ZeoR) were
      fused together to generate a bifunctional protein for the identification and
      selection of transfected mammalian cells. Expression of this hybrid selectable
      marker, GFP-ZeoR, was visually detected and conferred Zeocin resistance in
      prokaryotes and eukaryotes. This selectable marker provides a way to determine
      transient transfection efficiencies in tissue culture cells using fluorescence
      microscopy. Expression of the GFP-ZeoR was also used to identify and select
      stable mammalian cell lines expressing a heterologous gene. Selection was
      efficient and GFP fluorescence provides an excellent, noninvasive technique to
      monitor the success of Zeocin selection during the development of the stable cell
      lines. This hybrid resistance gene combines the functional properties of the
      Zeocin-resistance marker and GFP and should be useful for combined selection and
      fluorescence in a variety of organisms.

PMID- 9526662
TI  - FastTag Nucleic Acid Labeling System: a versatile method for incorporating
      haptens, fluorochromes and affinity ligands into DNA, RNA and oligonucleotides.
AB  - The FastTag Nucleic Acid Labeling System couples haptens, fluorochromes or
      affinity ligands to any nucleic acid by attaching a universal, photo-or heat
      activatable moiety to which any sulfhydryl-reactive compound can be linked. To
      demonstrate the versatility of the FastTag system, we have labeled DNA, RNA and
      oligonucleotide probes with a variety of maleimide-coupled moieties and have used
      these probes in several applications. In Southern hybridization analyses, RNA
      probes labeled using FastTag FL (fluorescein) detected 0.04 pg of target DNA.
      Human satellite DNA clones labeled using FastTag FL or FastTag Biotin detected
      the corresponding sequences in human chromosome spreads and interphase nuclei by
      fluorescence in situ hybridization. An antisense oligonucleotide probe cocktail
      complementary to human proinsulin transcripts labeled using FastTag DNP
      (dinitrophenyl) detected, in situ, the appropriate transcripts in pancreatic
      tissue sections. Oligonucleotide primers labeled with FastTag FL were used to PCR
      amplify a genomic DNA fragment, which was then detected immunologically. Finally,
      we discuss how DNA labeled with FastTag Fucose can be bound to a fucose-binding
      affinity matrix and eluted under mild conditions.

PMID- 9526663
TI  - The prevalence and nature of child sexual abuse in Queensland, Australia.

PMID- 9526664
TI  - Crossing the line from physical discipline to child abuse: how much is too much?

PMID- 9526665
TI  - The evaluation of Franco-Quebec victims of child sexual abuse and their mothers:
      the implementation of a standard assessment protocol.
AB  - OBJECTIVE: There were two aims: first, to evaluate the feasibility of applying a
      standard assessment protocol to Franco-Quebec victims of child sexual abuse and
      nonoffending mothers; and second, to compare results from an initial sample with
      available data from English-speaking samples. METHOD: A standard individual case
      study design was used for victims and mothers; and the satisfaction of the nine
      participating youth workers was assessed. Four self-report instruments for
      victims and five for mothers were chosen on the bases of workers' priorities,
      sensitivity to the impact of CSA, and the availability of published norms on
      English-speaking samples. Results are reported on 48 confirmed victims and 40
      nonoffending mothers. RESULTS: The protocol was favorably received by the CPS
      workers, supervisors and all mothers and victims. Percentages of clinically
      distressed victims varied from highs of 68% on the externalization difficulties
      of the Child Behavior Checklist and 67% for 2- to 6-year-olds on the Child Sexual
      Behavior Inventory, to lows of 10% on hostility symptoms and 13% on the
      Dissociation Scale of the Trauma Symptom Check for Children. The rate of symptom
      free children was lower (19%) and that of revictimization higher (30%) than most
      published estimates (Kendall-Tackett, Williams, & Finkelhor, 1993). Most mothers
      reported elevated emotional distress (depression, 59%) and symptoms of post
      traumatic stress (intrusiveness, 67%). Although 87% of mothers believed the
      allegations, only 45% offered adequate emotional support. CONCLUSION: The
      implementation phase of this research was successful, given the positive
      reactions of workers and clients. Results on standard instruments from this
      French-speaking sample were similar to profiles of English-speaking victims and
      their mothers but firm conclusions on appropriate norms will require larger
      samples, cross cultural contrasts, and the evaluation of additional variables.

PMID- 9526666
TI  - [Efficacy of a treatment program for sexually abused children].
AB  - OBJECTIVE: An evaluation study was conducted in order to evaluate the impact of
      the treatment program for sexually abused children. METHOD: Forty-one (41)
      children (aged 6-17 years), victims of a sexual abuse by a family member, were
      assessed at pre- and post-treatment (16 months following the pre-test). The
      evolution of children's psychological well-being was measured by the Children's
      Depression Inventory (CDI), the Picturial Scale of Perceived Competence and
      Acceptance for Young Children (PSPCA), the Children's Nowicki-Strickland Internal
      External control scale (CNS-IE), the Children's Action Tendency Scale (CATS), the
      Revised Children's Manifest Anxiety Scale (RCMAS), and the Pediatric Behavior
      Scale (PBS). A hierarchical multiple regression analysis was used to assess the
      strength of the relationship between the level of participation in both
      individual (including dyadic and family therapy) and group therapy and the
      evolution of Ss' psychological well-being. RESULTS: Results indicate that the
      child's mental health was generally positively related to the level of
      participation in individual therapy but not related or negatively related with
      the level of participation in group sessions except for the PBS. CONCLUSIONS:
      These results indicate the need: (a) to consider the adoption of a dose
      measurement in the appreciation of the therapeutic impact; (b) to have a better
      grasp of the nature and the effects of specific therapeutic activities included
      in a program; (c) to have a better understanding of the disparities observed
      between parents' and children's evaluation of the psychological status of the
      child.

PMID- 9526667
TI  - Adult attachment and long-term effects in survivors of incest.
AB  - OBJECTIVE: The aim of the study was to test the hypothesis that adult attachment
      is related to distress and personality disorders in incest survivors. METHOD:
      Adult female incest survivors recruited from the community participated in a
      structured interview (Family Attachment Interview; Bartholomew & Horowitz, 1991)
      and completed measures of current functioning (Impact of Event Scale, SCL-10,
      Beck Depression Inventory) and personality (MCMI-II). Complete data from 92 cases
      out of the total sample of 112 were analyzed. RESULTS: Analyses of variance
      suggested that attachment (as represented by a category) was significantly
      related to personality structure, with fearful individuals showing more avoidant,
      self-defeating, and borderline tendencies and preoccupied individuals showing
      more dependent, self-defeating, and borderline tendencies than secure or
      dismissing individuals. Results of hierarchical regression analyses suggested
      that attachment (as represented by four dimensions) was significantly associated
      with personality structure, depression and distress, and abuse severity with post
      traumatic stress disorder (PTSD) symptoms (intrusive thoughts and avoidance of
      memories) and depression. CONCLUSIONS: The findings demonstrated the propensity
      for insecure attachment among incest survivors. Sexual abuse severity and
      attachment have significant but distinct effects on longterm outcome; abuse
      characteristics predict classic PTSD symptoms and attachment insecurity predicts
      distress, depression, and personality disorders above and beyond any effects of
      abuse severity.

PMID- 9526668
TI  - Ad HoC conferences of hospital and community professionals in cases of
      hospitalized physically abused children.
AB  - OBJECTIVE: Although community interagency child protection teams are common and
      well described in the literature, they may not meet the needs of investigating
      agencies when children are hospitalized in tertiary medical facilities some
      distance from their homes. Sometimes, the communities in which they live do not
      have effective teams, or the information to be conveyed is highly technical. This
      report describes and assesses ad hoc multi-agency conferences with varying
      hospital and community agency participants, each conference devoted to a single
      hospitalized child suspected of having been abused. METHOD: A questionnaire
      devised by the authors was administered by telephone to 22 former conference
      participants from state social agencies, law enforcement units, and prosecuting
      attorney's offices. RESULTS: Most of the surveyed participants reported the case
      specific conferences to have been helpful, meeting their goals and affecting the
      outcomes of their cases. CONCLUSION: The conferences appear to have been
      worthwhile. Although they were associated with some disadvantages for the
      involved professionals and the sponsoring hospital, the disadvantages appeared to
      have been offset by the potential benefits for the children, families,
      participants, and hospital.

PMID- 9526669
TI  - Therapeutic treatment for physically abused children.

PMID- 9526670
TI  - The therapeutic treatment provided in cases involving physical child abuse: a
      description of current practices.
AB  - OBJECTIVE: The purpose of this study was to explore the therapeutic treatment
      provided by mental health practitioners in cases involving physical child abuse
      to describe generally the amount and type of treatment provided to the abused
      child and other significant people involved in the abuse. METHOD: An instrument
      was designed to determine what therapeutic treatment was provided by
      practitioners in the previous year and sent to 689 mental health workers in the
      state of Kentucky: Licensed Clinical Social Workers, Clinical Members of the
      American Association of Marriage and Family Therapists, and Kentucky Department
      of Social Services Caseworkers. RESULTS: The family was seen as the primary
      client most frequently with the focus of therapy being to provide a safe
      environment for the child or to improve family relationships. Abused children
      were found to receive only seven of the 23 sessions generally provided in these
      cases to overcome the deleterious effects of the abuse. CONCLUSIONS: The findings
      indicate that physically abused children may need more treatment to overcome
      their traumatic experiences. Since the family and the perpetrator have
      therapeutic requirements, these services need to be additional sessions. While
      the safety of the child is of paramount importance, the victim needs appropriate
      and effective treatment to surmount the detrimental consequences of the
      maltreatment.

PMID- 9526671
TI  - VLDL compositional changes and plasma levels of triglycerides and high density
      lipoprotein.
AB  - VLDL chemical composition is related to plasma levels of triglycerides and HDL
      cholesterol. We evaluated patients with primary hypertriglyceridemia with or
      without hypoalphalipoproteinemia and subjects with normotriglyceridemia with
      hypoalphalipoproteinemia. The pattern observed in all the groups was an
      enrichment in the triglyceride content of VLDL and in apo B-VLDL. Compared to
      controls, LpC-III:B levels were higher in hypertriglyceridemic patients with low
      or normal HDL-cholesterol levels (7.3 +/- 0.6 vs. 14.9 +/- 1.8 and 12.3 +/- 2.8
      mg/dl; P < 0.005 and P < 0.01, respectively) and LpE:B concentration was only
      increased in patients with hypertriglyceridemia and normal HDL-cholesterol levels
      (3.1 +/- 0.5 vs. 6.3 +/- 1.0 mg/dl; P < 0.01). The activity of the cholesteryl
      ester transfer protein was higher in hypertriglyceridemic patients with low HDL
      cholesterol levels than in controls (380 +/- 25 vs. 262 +/- 14% cholesteryl
      esters/ml.h; P < 0.001). The most atypical VLDL particle was found in patients
      who combined an accumulation of VLDL particles and a reduction in HDL-cholesterol
      concentration. These two parameters represent both ends of the cholesteryl ester
      triglyceride transfer, a crucial factor for VLDL chemical composition and HDL
      levels.

PMID- 9526672
TI  - A new enzymatic assay for selectively measuring conjugated bilirubin
      concentration in serum with use of bilirubin oxidase.
AB  - A new enzymatic assay for selectively measuring conjugated bilirubin
      concentration in serum with use of bilirubin oxidase (BOD) has been developed. At
      pH 5.5 BOD can oxidize only conjugated bilirubin in the presence of reagents such
      as sodium fluoride and N-acetylcysteine which can decrease BOD reactivity to
      unconjugated bilirubin and bilirubin covalently bound to albumin (delta
      bilirubin). The resulting decrease in absorbance at 450 nm is linearly related to
      the concentration of conjugated bilirubin in serum. The BOD in this new assay was
      confirmed to oxidize conjugated bilirubin, and neither unconjugated nor delta
      bilirubin, based on both its reactivity to unconjugated bilirubin and HPLC
      results. This assay was found to give satisfactory results, such as in terms of
      the range of measurement, the reproducibility of the results, the lack of
      interference with coexisting substances in serum and the stability of the reagent
      solutions, in practical applications. The serum conjugated bilirubin
      concentrations determined using this assay correlate well with those determined
      by the HPLC analysis. This assay can be used for accurate monitoring of changes
      in the conjugated bilirubin concentration in patient sera. These findings suggest
      that the conjugated bilirubin assay is useful for fractional determination of
      bilirubin in icteric sera.

PMID- 9526673
TI  - Elevated plasma nitrate in patients with crush syndrome caused by the Kobe
      earthquake.
AB  - We investigated the nitric oxide profile in the plasma of ten healthy controls
      and 29 patients hurt by the Kobe Earthquake. The levels of nitrite (NO2-) and
      nitrate (NO3-) were measured simultaneously by high-performance liquid
      chromatography (HPLC) with UV detection using the Griess reaction after the
      reduction of nitrate to nitrite. Arginine consumed in food or diet-derived
      nitrite had no effect on the plasma nitrite and nitrate contents of the healthy
      volunteers. Plasma nitrate was elevated in the crush syndrome patients; whereas
      neither nitrite nor nitrate was increased in patients with normal renal function.
      This finding suggests increased nitric oxide synthesis, decreased excretion of
      nitric oxide in the crush syndrome or both.

PMID- 9526674
TI  - Vitamin A and urolithiasis.
AB  - The effects of vitamin A deficiency on urolithiasis were investigated in male
      rats. A vitamin A-deficient diet caused important changes in the composition of
      the urine of the treated rats when compared with controls. One of the main
      effects was a decrease in the concentration of urinary glycosaminoglycans and
      zinc in the rats receiving the vitamin A-deficient diet. Significant differences
      were also found in plasma vitamin E and in the relation of vit E/vit A between
      treated and control groups but, in general, with no important differences in
      vitamin A. Nevertheless, significant differences in kidney content of vitamin A
      were observed between both groups. On the other hand, lesions of the cuboidal
      epithelium that covers the papillae in rats treated with the vitamin A-deficient
      diet were severe when compared with controls. The vitamin A and E plasma levels
      in urolithiasic humans were also investigated and compared with those found in a
      control group. No significant differences were observed in plasma vitamin A
      levels; nevertheless a significant increase in vitamin E and in the vit E/vit A
      ratio was clearly observed. These results could be related to a possible deficit
      of vitamin A in kidneys of stone formers, this being one of the diverse factors
      that can contribute to urolith development. Moreover, the deficit of important
      urinary crystallization inhibitors normally found in stone-formers, such as
      pyrophosphate and phytate, can also be related to the presence of low levels of
      renal vitamin A which prevents the enzymatic degradation of such inhibitors.

PMID- 9526675
TI  - Differential ability of cells to promote oxidation of low density lipoproteins in
      vitro.
AB  - Atherosclerosis and focal segmental glomerulosclerosis share some common
      histological features and it is speculated that they result from similar
      pathobiological mechanisms. There is strong evidence that oxidation of low
      density lipoprotein (LDL) may be an initiating event in atherogenesis and that
      oxidised LDL may also be involved in the glomerulosclerotic process. In vitro
      studies have demonstrated that cells present in the arterial intima and kidney
      derived cells promote LDL oxidation. The aim of this study was to compare LDL
      oxidation by kidney-derived human mesangial cells and proximal tubular cells,
      with human umbilical vein endothelial cells and the human monocyte cell line THP
      1. We used the thiobarbituric acid assay and agarose gel electrophoresis to
      measure the extent of LDL oxidation. Our results demonstrate that all of the cell
      types used had the ability to oxidise LDL significantly more than cell-free
      controls and that endothelial cells induced the highest degree of oxidative
      modification of LDL under our experimental conditions.

PMID- 9526676
TI  - Protein binding of homocysteine and other thiols in HeLa cell cultures after
      addition of homocysteine and copper ions.
AB  - Homocysteine can be viewed as the first risk factor for atherosclerosis, believed
      to exert its effects through a mechanism involving oxidative damage. Oxygen
      radicals are known to interact with a variety of macromolecules leading to lipid
      peroxidation, DNA strand breakage and a variety of changes in proteins, including
      thiol oxidation. The present study deals with the protein-binding of
      homocysteine, cysteine and glutathione in a human cell line culture exposed to
      homocysteine and copper ions in order to elucidate the possible role of
      homocysteine in cell injury and atherogenesis. It is shown that homocysteine has
      the highest tendency of the thiols investigated to create disulfide bonds with
      proteins. The interaction with the protein cysteine thiol groups, which are
      involved in the function of many enzymes, structural proteins and receptors might
      disturb many metabolic functions in the cell. This finding might therefore be one
      reason for the cell-damaging effects of homocysteine. Addition of reduced
      homocysteine to cell cultures decreased the intra- and extracellular proportions
      of protein-bound thiols except that of intracellular glutathione. In agreement
      with the pro-oxidative effects of copper ions, the findings in the present study
      showed an increase of the protein-bound fractions of all thiols after the
      addition of copper ions. Another finding is that increased (in the presence of
      100 mumol/l of copper ions) or decreased (in the presence of 100-2000 mumol/l of
      homocysteine) proportions of protein-bound fractions of the thiols in these short
      term experiments did not seriously affect the cells since the cell growth was
      unchanged.

PMID- 9526677
TI  - Increased concentration of circulating acid glycosaminoglycans in chronic
      lymphocytic leukaemia and essential thrombocythaemia.
AB  - To verify whether the increase in the number of circulating blood cells that
      synthesize glycosaminoglycans, B-lymphocytes or platelets, in proliferative
      disorders, may be associated with changes in the circulation of acid
      glycosaminoglycans, the serum and plasma concentrations of these polysaccharides
      have been measured in terms of their sugar components, following isolation and
      purification by chromatographic methods, in patients with chronic lymphocytic
      leukaemia or with essential thrombocythaemia and in healthy controls. In the
      patients, the concentrations of total circulating glycosaminoglycans and of both
      glucosamine-containing and galactosamine-containing serum glycosaminoglycans were
      significantly higher than in controls. These concentrations did not significantly
      correlate with the number of lymphocytes in patients with chronic lymphocytic
      leukaemia and of platelets in patients with essential thrombocythaemia.
      Analytical data suggest that excess glycosaminoglycans are mainly composed of
      chondroitin sulphate molecules and contain heparan sulphate structures.

PMID- 9526678
TI  - Improved assay of hepatic microsomal cholesterol 7 alpha-hydroxylase activity by
      the use of hydroxypropyl-beta-cyclodextrin and an NADPH-regenerating system.
AB  - Cholesterol 7 alpha-hydroxylase, the key enzyme in bile acid synthesis, has been
      implicated in atherosclerosis and gallstone disease. The aim of this study was to
      check if the use of hydroxypropyl-beta-cyclodextrin (HPBCD), a vehicle for
      solubilizing cholesterol, augmented the rate of 7 alpha-hydroxycholesterol
      formation in hamster liver microsomes compared to classical assays in which
      labeled cholesterol was delivered in Tween 80. We observed that [14C]cholesterol
      carried by HPBCD enhanced the sensitivity of the assay tenfold. However,
      linearity of 7 alpha-hydroxycholesterol formation with time was short because of
      the rapid transformation of 7 alpha-hydroxycholesterol into 7 alpha-hydroxy
      cholesten-3-one and 7 alpha,12 alpha-dihydroxy-cholesten-3-one when NADPH alone
      was present in the incubation medium. In order to avoid the transformation of 7
      alpha-hydroxycholesterol into 7 alpha-hydroxy-cholesten-3-one, which is
      essentially NAD(+)-dependent, but is also NADP(+)-dependent, NADPH (1 mmol/l)
      plus an NADPH-regenerating system must be present in the medium. In this improved
      assay, the optimal pH was 7.4 and the apparent Km for control and cholestyramine
      fed hamsters had a similar value of 315 mumol/l; linearity in the formation of 7
      alpha-hydroxycholesterol was also apparent after a relatively short time period
      (10 min), but with a markedly greater slope of the curve. With a short incubation
      time (6 min), microsomes from livers of hamsters (five and nine weeks old) that
      were fed with a commercial ground diet yielded rates of 7 alpha
      hydroxycholesterol formation of 115 +/- 10 and 150 +/- 16 pmol/min.mg protein,
      respectively, whereas microsomes from hamsters fed with a lithogenic sucrose-rich
      diet (five weeks old) yielded rates of 7 alpha-hydroxycholesterol formation of 77
      +/- 7 pmol/min.mg protein, which were significantly lower (-33%) than those of
      corresponding control hamsters. This improved cholesterol 7 alpha-hydroxylase
      assay is very sensitive, simple and rapid, and does not necessitate sophisticated
      equipment. It can be particularly useful for determining cholesterol 7 alpha
      hydroxylase activity in liver biopsies from dyslipidemic or lithiasic patients.

PMID- 9526679
TI  - Decreased expression of transforming growth factor beta 1 in blood plasma of
      guinea pigs fed vitamin C deficient diet.

PMID- 9526680
TI  - A rapid, highly-resolving and sensitive method for quantifying neuron-specific
      enolase using Helena Laboratories Cardio-Rep.

PMID- 9526681
TI  - Cassava fermentation and associated changes in physicochemical and functional
      properties.
AB  - Fermentation of cassava is an important processing technique followed in
      different parts of the world. Although fermentation is known to bring about vast
      changes in the physicochemical and functional properties of the tubers, attempts
      have seldom been made to consolidate and critically analyze the available
      information. Glaring inconsistencies and contradictions noticeable in some of the
      results reflect the differences and variations in the artisanal processes
      followed in the preparation of these products. It also stresses the need for a
      systematic study of not only the quoted products, but also a number of other
      fermented cassava products that have not been well documented.

PMID- 9526682
TI  - Barley: chemistry and value-added processing.

PMID- 9526683
TI  - The ontogeny of long-term memory over the first year-and-a-half of life.
AB  - This research documents the development of long-term memory in human infants from
      2 months through the end of the first year-and-a-half of life. In the initial
      study phase, we trained 6- to 18-month-old human infants in an operant task and
      tested them after increasing delays until they exhibited no retention for 2
      successive weeks. In the second phase, their data were combined with data
      previously obtained from 2- to 6-month-olds in an equivalent task. The resulting
      function revealed that the duration of retention increases monotonically between
      2 and 18 months of age. This increase was not due to age differences in original
      learning. This is the first systematic analysis of the course of long-term memory
      across an extended period of infant development that is based on standardized
      parameters of training and testing. It provides a reference function against
      which measures of retention from infants of different ages that are obtained in
      different memory tasks with different parameters can be meaningfully compared.

PMID- 9526684
TI  - Perinatal stimulation facilitates suckling onset in newborn rats.
AB  - The fetus' experience of birth derives from a sequence of stimulation provided by
      the mother's labor contractions, her licking and handling, and the contrasting
      environmental conditions of the uterus and outside world. In the present
      investigation, Day 21 fetal rats were externalized from the dam's body; subjects
      in one uterine horn were compressed by simulated uterine contractions while
      control subjects in the opposite horn were not compressed. All pups were Cesarean
      delivered, stroked, and exposed to a thermal environment simulating either room
      (21 degrees C), nest (33 degrees C), or intrauterine (36 degrees C) temperature.
      After 1-hr exposure to the experimental temperature, all pups were maintained at
      33 degrees C and tested for their suckling response to an anesthetized dam. When
      newborns were tested at 120 min postpartum, simulated contractions increased the
      probability of nipple attachment in pups exposed to 21 degrees C relative to
      noncompressed littermates maintained at the same temperature. Atypically warm
      postpartum conditions (nestlike or intrauterine) obviated the effects of
      compression by increasing suckling above the levels seen in noncompressed
      newborns exposed to the cool condition. Thus, compressions facilitate the
      achievement of suckling under thermal conditions resembling those typically
      encountered by the newborn rat.

PMID- 9526685
TI  - Importance of mother/young contact at parturition and across lactation for the
      expression of maternal behavior in rabbits.
AB  - We prevented mother/pup contact at parturition or across early or midlactation to
      investigate the importance of such interaction for maintaining material behavior
      in rabbits. When pup contact was prevented across lactation Days 1-7 or 11-17 (by
      anesthetizing multiparous mothers during the oxytocin-induced milk letdown;
      Experiment 1), nursing incidence was reduced to 40% and 83%, respectively, on the
      day following anesthesia withdrawal. Both groups also showed a decreased milk
      output, long latencies to initiate nursing, and several entrances into the nest
      box not associated with nursing. In Experiment 2 we prevented mother/litter
      contact at parturition to determine the specific role of pup contact at this
      time. We found a reduction in the incidence of nursing on postpartum Day 1 from
      80% (in control primiparous mothers) to 33%. By contrast, 100% of both deprived
      and control multiparous mothers displayed nursing on Day 1. These mothers also
      showed the unusual behaviors found in Experiment 1 and an extemporaneous nest
      building. We conclude that: (a) mother/young contact at parturition is crucial
      for establishing maternal responsiveness in primiparous does, (b) the experience
      acquired by raising a previous litter allows the retention of maternal
      responsiveness despite a lack of pup contact at parturition, (c) maternal
      responsiveness is maintained across early lactation by daily interaction with
      pups, and (d) interaction with pups across midlactation allows the finely tuned
      display of maternal behavior.

PMID- 9526686
TI  - Fear-potentiated startle responses in temperamentally different human infants.
AB  - Previous research has indicated that 4-month-old human infants who exhibit high
      degrees of motor activity and negative affect in response to the presentation of
      unfamiliar auditory and visual stimuli are likely to display behavioral
      inhibition as toddlers, while 4-month-old infants who display high degrees of
      motor activity and positive affect in response to the same stimuli are likely to
      be behaviorally exuberant toddlers. The present study examined baseline and fear
      potentiated startle eyeblink responses during a stranger-approach paradigm at age
      9 months in a group of infants, some of whom displayed high motor activity and
      negative affect and some of whom displayed high motor activity and positive
      affect at 4 months. The analyses revealed that the high motor/high negative group
      of infants exhibited a significantly greater increase in fear-potentiated startle
      amplitude at 9 months compared with the high motor/high positive group. There
      were no differences among groups of infants on baseline startle responses. These
      findings suggest that the origins of behavioral inhibition in early childhood may
      be linked to a low threshold for arousal in forebrain limbic areas.

PMID- 9526687
TI  - Effects of prenatal testosterone on sex and age differences in behavior elicited
      by stimulus pups in the rat.
AB  - From Days 14 to 19, pregnant Wistar rats were treated with either 2 mg of
      testosterone propionate (TP) or vehicle. Thirty-, 60-, and 90-day-old offspring
      were tested individually during 15 min daily on 4 days with a stimulus litter,
      and pup-oriented and non-pup-oriented behaviors were recorded. Sex differences in
      pup-oriented behaviors observed in oil groups were eliminated by TP treatment,
      which affected mainly females. Additionally, TP treatment increased the frequency
      of self-grooming and decreased the time spent near the pups and the frequency of
      sniffing and pawing only at 90-days of age. Hiding behavior only occurred at 30
      days of age, while pawing near the pups and lying-down behavior was observed
      mainly in adults. Results show that sex differences in behavior are present
      before subjects become sensitized to show evident maternal behavior, and suggest
      that prenatal androgens play an important role in the manifestation of these sex
      differences and that its effects depend on developmental factors.

PMID- 9526688
TI  - A method for regulating the duration of pregnancy and the time of parturition in
      Sprague-Dawley rats (Charles River CD strain).
AB  - A method of shifting the dark phase of the 12/12 hr photoperiod cycle on Day 7 of
      pregnancy is described for regulating the duration of pregnancy to 22 days and
      assuring that most parturitions take place between 1100 and 1500 hr. This method,
      in addition, has the added convenience that matings can occur during normal
      laboratory hours between 0700 and 1900 hr during the dark phase of the
      photoperiodic cycle. Litter sizes are normal (mostly 14-16 pups) and postpartum
      estrus behavior occurs at the normal interval of 4 to 11 1/2 hr after
      parturition.

PMID- 9526689
TI  - Hypertension in Alaska Natives: association with overweight, glucose intolerance,
      diet and mechanized activity.
AB  - OBJECTIVE: Determine the prevalence of hypertension in Alaska Natives and
      evaluate risk factors. DESIGN: Population-based univariate and multivariate
      analysis of blood pressure in 1124 Alaska Natives over 20 years of age. RESULTS:
      The sample had mean: age 45 years, body mass index 27, systolic pressure 123 mmHg
      and diastolic pressure 73 mmHg. The age-adjusted rate of hypertension > or =
      160/95 mmHg was 9.1% and 6.8% among Athabascan Indians and Yup'ik Eskimos,
      respectively. After controlling for age and sex there was significantly more
      hypertension among Athabascan Indians (OR = 1.53, CI = 1.07-2.2, p = 0.019)
      compared to Yup'ik Eskimos. Race was significantly associated with blood pressure
      > or = 140/90 when controlled for age and overweight (p = 0.01, OR = 0.78, CI =
      0.69-0.95). The presence of hypertension was significantly associated with the
      following: intake of non-indigenous food (p = 0.01); mechanized activities (p =
      0.01); and glucose intolerance in both women (p = 0.043) and men (p = 0.001).
      Multiple regression analysis revealed age (OR = 1.06, CI = 1.05-1.08) and
      overweight in both men (OR = 3.02, CI = 1.85-4.93) and women (OR = 2.76, CI =
      1.81-4.19) to be significantly associated with BP > or = 140/90. CONCLUSION:
      Hypertension is no longer rare in Alaska Natives and is associated with
      overweight, non-indigenous diet, mechanized activities, and glucose intolerance.

PMID- 9526690
TI  - A Native American community initiative to prevent diabetes.
AB  - The increasing prevalence of obesity and diabetes in the Mohawk Community of
      Akwesasne led to the formation of an advisory group who's mission was to increase
      community awareness and strengthen the infrastructure necessary to create a
      community coalition to promote healthy lifestyles. The methodology used to reach
      these goals included: obtaining an understanding of the community's knowledge,
      attitudes and behaviors about diabetes, diet and exercise using semi-structured
      interviews and focus groups; analyzing data from a case control study of diabetes
      and it complications using a medical record review; exploring methods for
      evaluating energy expenditure in children; and identifying influential community
      members and organizations. In the last 50 years people had become less physically
      active and high fat, high caloric foods were more available. Community members
      were concerned about health and the well-being of their children, had knowledge
      about healthy lifestyles but lacked confidence and social support for bringing
      about desired changes. A strong association was documented between diabetes,
      smoking cigarettes, high blood cholesterol and vascular disease in this
      community. Approximately 100 persons participated, several hundred received the
      results in presentations to 17 community organizations, two public fora, letters
      to participants and articles in local newspapers. Fifty persons and 29 businesses
      or organizations regarded as strong advocates of healthy lifestyles were
      identified. From these a community coalition was formed and has initiated
      programs to reduce dietary fat and increase physical activity in young children.

PMID- 9526691
TI  - Classifying ethnicity utilizing the Canadian Mortality Data Base.
AB  - The study of ethnic differences in disease is a methodological challenge as
      ethnicity is often not identified in existing datasets and surrogate measures
      need to be used. We have developed a novel methodology combining last name and
      country of birth to study mortality patterns of Canadians of South Asian (SA) and
      Chinese (CH) ethnic origin and have compared death rates among SA, CH, and White
      (WH) Canadians. METHODS: SA and CH were identified in the Canadian Mortality Data
      Base (CMDB) using the last name and country of birth of the deceased. Records of
      people who had been born in countries with large South Asian and Chinese
      populations (e.g. India, Pakistan, China, Hong Kong) were selected and manually
      screened by last name. A name directory was then created of distinct South Asian
      and Chinese names and this directory was used to search all other records in the
      CMDB for SA and CH deaths. Where necessary, other identifying characteristics
      such as first name and parents' last name were also used. Population counts were
      obtained from the Census self-reported question on ethnicity for SA and CH. WH
      were identified as non-immigrant Canadians who were neither SA nor CH. The method
      of assigning ethnicity in the CMDB and Census were assessed for comparability and
      issues of validity and reliability were addressed. RESULTS: Using this method,
      10,989 SA and 21,548 CH deaths were identified. There was marked heterogeneity in
      birthplace, with only 56% of SA born in South Asia and only 74% of CH born in
      Greater China. Last names had high validity for self-reported ethnicity in a
      population sample of SA and were highly reproducible. Mortality rates varied
      dramatically between groups studied. SA and WH had high rates of ischemic heart
      disease while stroke mortality was similar among all three groups. Cancer death
      rates were high in CH and WH and much lower in SA. CONCLUSION: Last names and
      country of birth can be used to determined ethnicity of SA and CH with validity
      and reliability, and leads to a more accurate classification than country of
      birth alone. The contrasting patterns observed in mortality from major causes of
      death suggest many interesting hypotheses for further study.

PMID- 9526692
TI  - Reproducibility and validity of a food frequency questionnaire in European and
      Polynesian New Zealanders.
AB  - The reproducibility and validity of a self-administered 142-item food-frequency
      questionnaire (FFQ) was assessed in a population comprising 124 European and 52
      Polynesian (17 Maori and 35 Pacific Island) New Zealanders aged 40-65 years.
      Reproducibility correlation coefficients, determined by administration of the
      same questionnaire on two occasions 3 years apart, were higher in European than
      Maori and Pacific Island participants, ranging from 0.47 to 0.87 in Europeans
      (median 0.66) and from 0.41 to 0.79 in Maori and Pacific Island people (median
      0.44). In general, there were no significant differences in mean nutrient intakes
      calculated from the two FFQs by Europeans or Maori and Pacific Island
      participants despite their cultural and language differences. When the FFQ was
      compared with a 3-day food diary in a subsample of 101 Europeans, 15 Maori and 22
      Pacific Islanders, the validity was good for most nutrients, with overestimation
      of a few nutrients in each ethnic group. Correlation coefficients between the 3
      day food diary and FFQ ranged from 0.41 to 0.81 in Europeans (median 0.48) and
      from 0.36 to 0.56 in Maori and Pacific Island people (median 0.55). Ratios of
      energy intake to resting metabolic rate suggested that Maori and Pacific Island
      people were more likely to underestimate their habitual energy intake by the 3
      day diet diary method compared to Europeans, but that Europeans were more likely
      to underestimate total energy intake by the food frequency method and Pacific
      Island participants to overestimate it. Obese Europeans and Maori were more
      likely to under-report dietary intakes by the 3-day diary method. We conclude
      that our FFQ performed better in European than Maori and Pacific Island
      participants.

PMID- 9526693
TI  - Variations in health behaviours among inner city 12-year-olds from four ethnic
      groups.
AB  - OBJECTIVES: To describe factors that contribute to variations in health-related
      behaviours and attitudes among inner city 12-year-olds. To see if there was an
      identifiable patterning by ethnic group. DESIGN: Semi-structured interviews with
      a stratified sample of 12-year-old students and their parents from four ethnic
      groups, attending state secondary schools in two inner London boroughs. RESULTS:
      Bangladeshi young people were significantly more likely to receive school meals.
      There was no variation in reported snacking between the groups. Girls and
      Bangladeshi students were less likely to report exercising outside school (33% of
      Bangladeshi boys reported not exercising outside school compared to 5% of boys
      from all other groups). Bangladeshi boys and their parents were more likely to
      report that bullying or worries about racial violence prevented them from going
      out after school. White young people were more likely to report experimenting
      with and the regular use of cigarettes and alcohol. Use of alcohol and cigarettes
      was also associated with gender, religion and strength of religious observance.
      White parents were the least likely to report restricting their child's social
      activities as a way of influencing behaviour and expressed more concerns about
      their child's potential for health-damaging behaviour than parents in all other
      groups. CONCLUSION: This study shows that ethnicity alone is insufficient and
      inadequate in explaining variations in health behaviours among inner city
      teenagers. A complex mix of personal, cultural and social factors including
      ethnicity shape the behaviours and attitudes of these young people.

PMID- 9526694
TI  - Is there an increased prevalence of severe learning disabilities among British
      Asians?
AB  - Age-specific prevalence rates for learning disabilities among the Asian
      communities in three Metropolitan Boroughs in the North of England are presented.
      These data indicate that: (1) below school age there is little difference in the
      apparent prevalence of severe learning disabilities between the Asian and non
      Asian communities; (2) between 5 and 34 years of age, however, the apparent
      prevalence of severe learning disabilities is approximately three times higher
      among the Asian community when compared with the non-Asian community.

PMID- 9526695
TI  - It's more than literacy: the assimilation effect of the translation model.
AB  - Availability and access to correct information is a pre-requisite for people to
      be able to make informed decisions about their health. This paper will examine
      the effect of the sole reliance on translation in producing health promotion
      materials for people from Non English Speaking Background (NESB). In Australia
      since 1978 there has been a considerable quantitative increase in health-related
      information translated from English into other languages. The translation of
      pamphlets from English into other languages presents health educators with a
      number of problematic issues which often drastically undermine the material's
      effectiveness. One of the main concerns this paper sets out to explore is that
      translated information is decontextualised from the sets of knowledge and
      meanings of the population group to whom the information is directed. Thus, the
      cultural context underpinning the original version is transferred to different
      cultural contexts which are treated as homogeneous groups. The paradox here is
      that the translation model developed as a means of redressing the inequities
      created by the assimilation policy of the Australian post-war period, in practice
      maintains the philosophy that underpinned that policy. This can result in a
      disempowering experience for the community.

PMID- 9526696
TI  - Health outcomes among African American and Caucasian adults following a
      randomized trial of an asthma education program.
AB  - OBJECTIVES: Re-analysis of a randomized trial of an asthma education program
      designed to assess the effects of the intervention on emergency department
      visits, limited days of activity and asthma knowledge and beliefs separately for
      African American and Caucasian adults with asthma. DESIGN: Two hundred and forty
      one respondents between the ages of 18 and 70 were evaluated in two emergency
      departments (one inner city and one suburban location) of a large, midwestern
      health care system and were randomized to an intervention or control group.
      RESULTS: Regardless of race, members of the intervention group showed a decrease
      in the number of post-intervention emergency department visits (ANOVA interaction
      between race and group effect p value = 0.93). The greatest decrease occurred
      during the first four post-intervention months. No differential effect of the
      asthma education intervention by race was found on the change in asthma knowledge
      and beliefs over the study period (ANCOVA interaction between race and group
      effect p value = 0.60). CONCLUSION: This study demonstrates that post
      intervention, both African American and Caucasian study participants showed a
      decrease in emergency department visits and an increase in asthma self
      management. This finding is especially important for African Americans, who face
      increasing asthma mortality and morbidity.

PMID- 9526697
TI  - Trans-kingdom conjugation offers a powerful gene targeting tool in yeast.
AB  - Gene targeting is one of the powerful techniques used to investigate eukaryotic
      genes. In a typical eukaryotic microbe, Saccharomyces cerevisiae yeast, we
      examined trans-kingdom conjugation between Escherichia coli bacterium and yeast
      as a gene targeting tool. Here, it is shown that trans-kingdom conjugation
      effectively induced gene replacement even on yeast's target loci (e.g. ura3-52
      allele) which is never targeted by conventional transformation. This clearly
      indicates that trans-kingdom conjugation offers a very powerful gene targeting
      tool in yeasts. In fact, Southern hybridization analysis of transconjugants
      distinctly verified the accuracy in the conjugative gene replacement. The
      efficiency of gene replacement was about 0.4 x 10(-7) per recipient yeast. This
      is enough to sustain gene targeting with gene replacement by trans-kingdom
      conjugation. We also discuss the mechanism of conjugative gene replacement.

PMID- 9526698
TI  - Cloning, sequence analysis and expression in E. coli of the DNA polymerase I gene
      from Chloroflexus aurantiacus, a green nonsulfur eubacterium.
AB  - We have cloned and sequenced the polA gene from Chloroflexus aurantiacus, a green
      nonsulfur eubacterium, and expressed the recombinant protein in Escherichia coli.
      One open reading frame encodes a protein with 942 amino acids showing 38%
      identity with DNA polymerase I from E. coli. Sequence alignments with other
      members of DNA polymerase family A and analysis of the separate domains show that
      the central 3'-5' exonuclease domain is 30% identical to the corresponding E.
      coli domain and that three sequence motifs associated with 3'-5' exonuclease
      activity are conserved. Also, a protein fraction from E. coli expressing the
      Chloroflexus polymerase contains a thermostable 3'-5' exonucleolytic activity,
      indicating that this activity is present in the enzyme, in agreement with the
      sequence analysis. The N-terminal 5'-3' exonuclease domain and the C-terminal
      polymerase domain show 31 and 46% identity, respectively, with the corresponding
      E. coli domains and all sequence motifs associated with these two enzymatic
      activities also are conserved. Since several DNA polymerase I enzymes lack the
      proofreading activity associated with the central domain it has been suggested
      that the ancestral polA gene contained only the two more conserved N- and C
      terminal domains and that the proofreading 3'-5' exonuclease domain was
      introduced later in those eubacterial branches that have this activity. Our data
      indicate a different scenario where the ancestral polA gene contained both the
      exonucleolytic activities in addition to the polymerase activity and where
      several eubacterial branches lost the polymerase-associated proofreading activity
      during evolution.

PMID- 9526699
TI  - ZFX and ZFY loci in water buffalo (Bubalus bubalis): potential for sex
      identification.
AB  - In the present study a small region of ZFX and ZFY loci in buffalo have been
      amplified by polymerase chain reaction (PCR). Restriction fragment length
      polymorphism (RFLP) was also uncovered that can distinguish between male and
      female buffalo DNA. The study also found a second copy of the ZFX loci (ZFXR)
      present in both male and female. Sequence analysis showed that ZFXR has a single
      base deletion that results in a redundant putative protein.

PMID- 9526700
TI  - Cre/loxP-mediated excision and amplification of large segments of the Escherichia
      coli genome.
AB  - The isolation and amplification of large, predetermined segments of a genome from
      its host have been explored. The prototype of our approach was the excisional
      replication of some viruses such as the lambda-lysogen. Similar machinery was
      used to excise and amplify large genomic segments of Escherichia coli in its
      host. Two loxP sequences for a site-specific recombinase Cre, together with a
      conditional replication origin (pi-dependent gamma-ori), were inserted into the
      genome by homologous recombination at predetermined sites, 50-100 kb apart. Cre
      and pir200 which encodes the site-specific recombinase Cre and an ori-specific
      replication protein pi, respectively, were also introduced into the genome. The
      predetermined genomic segments flanked by the loxP sequences were excised and
      amplified upon induction of the cre and pir200 genes which were under the control
      of the tet promoter. This excised and amplified DNA could be easily purified as a
      large plasmid. This procedure can provide an alternative to conventional cloning
      methods by obtaining predetermined large genomic segments directly from the
      original organisms. In this study, using the Cre/loxP site-specific recombination
      and pi/gamma-ori replication system of plasmid R6K, a procedure was devised that
      could isolate a large segment of the E. coli genome and demonstrated the
      feasibility of the procedure by excising and amplifying the 50-kb trg-narZ and
      100-kb trg-hipA regions of the E. coli W3110 genome.

PMID- 9526702
TI  - Assay of transfection rate in insect cells on a single cell level.

PMID- 9526701
TI  - Application of nested PCR and mass spectrometry for DNA-based virus detection:
      HBV-DNA detected in the majority of isolated anti-HBc positive sera.
AB  - DNA preparations from three different groups of serum samples were examined for
      HBV-DNA via a nested polymerase chain reaction assay (lower detection limit: 10
      viral genomes in 100 microliters serum): Group I consisted of 11 uninfected
      control sera, group II consisted of sera obtained from 11 HBV infected patients
      and group III consisted of 21 isolated anti-HBc positive samples. The 21 samples
      from group III were HBV-DNA negative according to a conventional non-nested PCR
      assay and hybridization with a 32P-labelled probe. Using nested PCR and mass
      spectrometry, HBV-DNA was detected in none of group I and in all of group II
      samples. In 11 out of 21 (52%) of the isolated anti-HBc positive sera from group
      III, HBV-DNA was detected. No correlation was observed between HBV-DNA positivity
      and anti-HBc titers. Matrix-assisted laser desorption/ionization time-of-flight
      (MALDI-TOF) mass spectrometry provided a fast, sensitive and non-radioactive
      assay for the detection of PCR products without the need for gel electrophoresis
      or hybridization with labelled probes.

PMID- 9526704
TI  - Implications of using follicle-stimulating hormone preparations depleted of
      luteinizing hormone to achieve follicular growth in in vitro fertilization.
AB  - We aimed to compare the outcome of in vitro fertilization (IVF) treatment using
      follicle-stimulating hormone (FSH) containing gonadotropins with human menopausal
      gonadotropin (hMG) containing gonadotropins for ovarian stimulation. A
      retrospective analysis of 82 patients undergoing IVF in a private fertility
      clinic was performed over a specific period of time. Eighteen women received hMG,
      20 received Normegon and 44 received FSH. In addition, 17 of these patients
      received hMG in one cycle and FSH in the other. The main outcome measures studied
      were duration of treatment, dose of gonadotropins required to achieve optimum
      follicular growth, number and size of follicles, endometrial thickness, serum
      estradiol concentrations, number of oocytes retrieved, pregnancy rates and the
      incidence of ovarian hyperstimulation syndrome (OHSS). At the time of
      administration of human chorionic gonadotropin (hCG), the mean (+/- SD) serum
      estradiol concentrations in patients treated with preparations containing FSH and
      luteinizing hormone (LH) in a ratio of 1:1 was 10,044.3 +/- 5378.8 pmol/l
      compared with 6819.5 +/- 2597.9 pmol/l in patients treated with preparations with
      FSH and LH in a ratio of 3:1 and 7369 +/- 4300 pmol/l in patients treated with
      FSH. The differences between the first and the second two groups were significant
      (p < 0.05). Endometrial thickness in the three groups of patients were 11 +/- 1.7
      mm, 11 +/- 1.5 mm and 9.7 +/- 1.5 mm, respectively (p < 0.001). Comparing cycles
      of treatment with hMG and FSH in the same patient, we found significantly higher
      estradiol levels, thicker endometrium, more developing follicles and a shorter
      duration of treatment in the hMG-treated cycles compared with those in FSH
      treated cycles. However, there were no differences between the incidence of OHSS
      or the pregnancy rates between the three treatment groups. With the advent of
      recombinant human FSH and the shortage of LH-containing preparations, it is
      important to note that serum estradiol concentrations on the day of
      administration of hCG underrepresent the degree of follicular maturation. In the
      context of the use of a 'long' protocol of gonadotropin-releasing hormone (GnRH)
      analog therapy and LH-depleted gonadotropin preparations, serum estradiol is no
      longer a reliable marker of follicle development.

PMID- 9526703
TI  - Shortage of glutamine (CAG) homopolymeric repeats suppresses the expression of
      the androgen receptor in familial cases with complete androgen insensitivity
      syndrome.
AB  - The androgen receptor gene of two familial cases with complete androgen
      insensitivity syndrome was analyzed. The shortage of glutamine homopolymeric
      repeats (13 repeats) in the N-terminal domain of the androgen receptor of the
      patients was identified by DNA sequence analysis. In vitro transfection
      experiments with the patients' androgen receptor gene indicated that the
      expression of the androgen receptor in transfected COS-7 cells was decreased by
      10% as compared to that of the wild type androgen receptor gene. The thermal
      stability of the 5 alpha-dihydrotestosterone-androgen receptor complex was also
      partially impaired. The capacity of the androgen receptor to activate target gene
      transcription was partially disturbed in a luciferase assay. The shortened
      glutamine homopolymeric repeats might therefore be related to the pathogenesis of
      complete androgen insensitivity syndrome.

PMID- 9526706
TI  - Premature ovarian failure: steroid synthesis and autoimmunity.
AB  - The androgen biosynthesis and autoimmunity of 25 patients with premature ovarian
      failure (POF) and 18 control subjects with normal cycles were examined. Serum
      levels of dehydroepiandrosterone sulfate (DHEAS), 17-hydroxyprogesterone (17
      OHP), androstenedione, and testosterone were analyzed in POF patients with or
      without organ-specific autoimmunity, and the results compared with those of women
      with normal ovarian function. The comparative analysis of DHEAS, 17-OHP,
      androstenedione and testosterone showed that POF patients had significantly lower
      values than normal women (DHEAS, androstenedione and testosterone p < 0.01, 17
      OHP p < 0.05). Furthermore, we found one or more organ-specific autoantibodies in
      11 patients with POF (44%), while only one woman in the control group showed
      autoimmunity (antithyroid microsome) (5.5%). Only one patient had both anti
      ovarian and anti-adrenal antibodies (4%). The comparison of androgen levels in
      POF patients with or without autoimmunity revealed a statistically significant
      reduction of DHEAS levels in POF patients with organ-specific autoimmunity (p <
      0.01). These data reveal the reduction in androgen synthesis in POF patients,
      particularly in those with organ-specific autoimmunity.

PMID- 9526705
TI  - Leukemia inhibitory factor (LIF) production by human decidua and its relationship
      with pregnancy hormones.
AB  - The expression of leukemia inhibitory factor (LIF) by murine uterus was shown to
      be regulated by maternal hormones and was not dependent on the presence of an
      embryo. The objective of this study was to investigate whether in humans the
      secretion of LIF during early pregnancy is under maternal control and whether its
      production is correlated with pregnancy hormones, progesterone and beta-human
      chorionic gonadotropin (beta hCG). To exclude the possibility of paracrine
      interaction of decidua with trophoblast, we examined the secretion of LIF in
      women with extrauterine pregnancy. The present study was designed as a
      prospective, blinded, clinical and immunobiochemical study. The endometrial
      biopsies were performed on 12 women during surgery for ectopic pregnancy. On the
      same day, the level of progesterone and beta hCG in maternal plasma was examined.
      LIF concentration was determined in supernatants taken from cultured decidual
      explants. LIF production by decidual culture explants was found in all women with
      an ectopic pregnancy (Median 5015 pg, range 1389-19,304 pg). There was no
      correlation between the LIF production and the term of pregnancy, or with the
      level of circulated beta hCG (p > 0.05). However, when the concentration of
      progesterone in circulating plasma was less than 5 ng/ml, the secretion of LIF
      was 2.3-fold higher as compared to women who had progesterone levels of more than
      5 ng/ml (p < 0.01). Therefore, we conclude that LIF is actively produced by human
      decidua and that the production of this cytokine does not depend on the presence
      of fetotrophoblast. This study demonstrates for the first time that progesterone
      downregulates the secretion of LIF in the decidua during early pregnancy.

PMID- 9526707
TI  - Effects of estradiol and an aromatase inhibitor on progesterone production in
      human cultured luteal cells.
AB  - The human corpus luteum produces both estradiol and progesterone. It is well
      known that there are both autocrine and paracrine systems for the regulation of
      the corpus luteum and that estradiol regulates the progesterone production of the
      corpora lutea of some other species. To assess the direct effects of estrogen on
      human luteal function, we performed cell culture experiments. A low concentration
      of estradiol, almost equal to the amount of estradiol produced by human cultured
      luteal cells, directly stimulated progesterone production. 4-Cyclohexylaniline,
      an aromatase inhibitor, significantly reduced both progesterone production and
      estradiol production. Levels of estradiol higher than the levels that cultured
      human luteal cells themselves produced significantly reduced basal progesterone
      production and also significantly reduced human chorionic gonadotropin (hCG),
      forskolin and dibutyryl-cyclic AMP-stimulated progesterone production. According
      to these data, high doses of estradiol produced a luteolytic action which widely
      inhibited the steroidogenesis process. In conclusion, our results indicated that
      estradiol in part regulates progesterone production physiologically and blocks
      progesterone production in a pharmacological or pathological state in the human
      corpus luteum.

PMID- 9526708
TI  - Beta-endorphin response to oral glucose tolerance test in obese and non-obese pre
      and postmenopausal women.
AB  - Beta-endorphin (beta-EP) is a neuropeptide involved in several brain functions,
      regulating the reproductive axis and behavioral changes. Estrogens play a
      modulatory role on circulating levels of beta-EP in women. Previous clinical
      studies have demonstrated high plasma beta-EP levels in obese subjects and
      increased beta-EP release after an oral glucose tolerance test (OGTT) in normal
      or obese women. The aim of the present study was to evaluate plasma beta
      endorphin levels in response to an OGTT in pre- and postmenopausal obese and non
      obese women, in order to investigate if the decrease in gonadal steroid levels at
      menopause could modify in a different manner the control of beta-endorphin
      release in response to glucose administration. A group of 24 normal women (age
      range 45-55 years) were included in the study. The patients were subdivided in
      four groups of six subjects each: group A, premenopausal women with body mass
      index (BMI) < 25 (control); group B, premenopausal women with BMI > 25 (obese);
      group C, post-menopausal women with BMI < 25 (control); group D, postmenopausal
      women with BMI > 25 (obese). All women were studied between 8.30 and 9.00 am,
      after overnight fasting, and underwent an OGTT. In obese premenopausal women,
      basal plasma beta-EP levels were significantly higher than in non-obese women (p
      < 0.01). In postmenopausal women, regardless of body weight, low basal plasma
      beta-EP levels were found. A significant increase in plasma beta-EP levels, at 30
      and 60 minutes after oral glucose ingestion, was shown in control premenopausal
      women. No significant modifications to OGTT were shown in plasma beta-EP levels
      in the other three groups of women. In conclusion, while in premenopausal women
      the response of plasma beta-EP levels to OGTT is maintained, in postmenopause
      there is a lack of response to OGTT. This suggests that beta-EP release is
      dependent upon gonadal steroids, while it is only in part influenced by body
      weight.

PMID- 9526709
TI  - Hashimoto's disease in a papillary carcinoma of the thyroid originating in a
      teratoma of the ovary (malignant struma ovarii).
AB  - Adenocarcinomas represent a relatively rare complication of a cystic teratoma of
      the ovary. Those of thyroid origin have been reported in only a few cases. In
      this paper we report a case of papillary carcinoma of the thyroid arising from a
      cystic teratoma. The patient had no thyroid symptoms, but because of the presence
      of antimicrosomal and antithyroglobulin antibodies the diagnosis of Hashimoto's
      disease was made.

PMID- 9526711
TI  - Nongenomic effects of neurosteroids.
AB  - This review summarizes the current knowledge about the synthesis, the mechanism
      of action, and the effects of neurosteroids in the central nervous system.
      Particular attention is paid to the nongenomic actions of neurosteroids, which
      are discussed in relation to their clinical relevance for physiological and
      pathological states.

PMID- 9526710
TI  - Estrogen replacement therapy and cardiovascular protection: lipid mechanisms are
      the tip of an iceberg.
AB  - Cardiovascular disease remains a major cause of mortality among postmenopausal
      women. After menopause, atherogenesis is promoted by a number of metabolic and
      vascular changes. A multitude of observational clinical studies have come to the
      conclusion that estrogen replacement therapy (ERT) reduces cardiovascular risk by
      approximately 50% and that estrogen's favorable effects on the lipid profile can
      explain only 25-50% of the overall observed reduction. Estrogens are now known to
      have potent anti-atherogenic properties through lipid and non-lipid mechanisms;
      both will be highlighted in view of the recent literature. Estrogens induce
      favorable changes on lipids and lipoproteins, partly by increasing HDL
      cholesterol and decreasing both LDL-cholesterol and lipoprotein (a). Non-lipid
      mechanisms of estrogen action include decreasing insulin resistance, serum
      fibrinogen, factor VII and plasminogen activator inhibitor-1 (PAI-1). Moreover,
      estrogens maintain endothelial cell integrity, decrease expression of adhesion
      molecules, lower systemic blood pressure, promote vasodilatation, decrease
      platelet aggregability, inhibit vascular smooth muscle cell proliferation,
      possess potent antioxidant and calcium antagonist activities, inhibit adrenergic
      responses and downregulate platelet and monocyte reactivity. Also mentioned are
      recent reports linking estrogen to the renin-angiotensin system, relaxin,
      serotonin and homocysteine. What was once thought of as a simple action is now
      being increasingly appreciated as a complex, multifaceted mechanism, which serves
      to prove that estrogen is a powerful cardiovascular agent.

PMID- 9526712
TI  - Toward a pure best interests model of proxy decision making for incompetent
      psychiatric patients.

PMID- 9526714
TI  - Do forensic offenders receive harsher sentences? An examination of legal
      outcomes.

PMID- 9526713
TI  - Involuntary admissions and coercive measures in psychiatric care. Registered and
      reported.

PMID- 9526715
TI  - Making risk predictions without an instrument. Three years' experience of the new
      Swedish law on mentally disordered offenders.

PMID- 9526717
TI  - Psychopathology in police custody.

PMID- 9526716
TI  - Implementation of order of compulsory ambulatory treatment in Jerusalem.

PMID- 9526718
TI  - Preventing violent re-offending in not criminally responsible patients. An
      evaluation of a continuity of treatment program.

PMID- 9526719
TI  - Impact of solitary confinement on hospitalization among Danish prisoners in
      custody.

PMID- 9526720
TI  - Modification of criminal law and its impact on psychiatric expert opinions.

PMID- 9526721
TI  - An exploration on the effects of marijuana on eyewitness memory.

PMID- 9526723
TI  - Maximizing participation by black Americans in population-based diabetes
      research: the Project DIRECT pilot experience.
AB  - Diabetes and its associated complications and risk factors have a higher
      prevalence among blacks than whites. To reduce the burden of diabetes within the
      black community, research is needed to assess the behavioral, social, and
      environmental correlates associated with this disproportionate burden. Because of
      some well known instances of historical exploitation and abuse from medical and
      public health research conducted in black communities, this population has little
      enthusiasm for additional research, despite pressing health needs. This paper
      describes the process used to eliminate barriers and enhance trust between the
      target community and the researchers conducting a population survey of diabetes
      in Wake County, North Carolina. A community advisory board was organized to (1)
      review the survey instruments and methodologies, (2) identify persons from the
      community to serve as interviewers, and (3) promote the survey using the major
      local communication channels. The response rate to both the household survey and
      the comprehensive medical exam was 77%. Eighty-one percent of eligible black
      respondents completed the household exam and 80% completed the comprehensive
      medical exam. Advantages of building collaborative relationships between the
      community and research team are discussed.

PMID- 9526722
TI  - Inner city primary care providers' breast cancer screening knowledge:
      implications for intervention.
AB  - Low income and minority women continue to have relatively low breast cancer
      screening rates. Since physician recommendation is one of the most important
      determinants of mammography participation, we aimed to characterize the breast
      cancer screening knowledge of primary care providers serving a socially
      disadvantaged population. The study was conducted at the Adult Medicine Clinic of
      Seattle's county hospital. All attending physicians, resident physicians, and mid
      level practitioners were asked to complete a questionnaire in the spring of 1995.
      Forty-nine of 52 (94%) eligible providers completed the survey. The respondents
      generally agreed with published guidelines for screening mammography use. In
      contrast, they had relatively low levels of knowledge about breast cancer risk
      factors and the effectiveness of other breast cancer screening methods.
      Additionally, providers tended to over-estimate their breast cancer screening
      knowledge and skills. For example, 69% believed that they could answer patients'
      questions about mammography, but only 23% were aware of Medicaid's reimbursement
      policy for the procedure. For some variables, attending physicians were no more
      knowledgeable than resident physicians. Our results reinforce the need for
      increased preventive care training in medical schools and primary care residency
      programs. Educational programs for providers serving disadvantaged populations
      might usefully focus on pragmatic issues such as institutional costs and public
      payer reimbursement policies.

PMID- 9526724
TI  - Substituting home care for hospitalization: the role of a quick response service
      for the elderly.
AB  - The purpose of the present study was to examine the role of a rapid access home
      based service as a means for the elderly to avoid admission to an acute-care
      hospital. The setting for the study included emergency departments in three acute
      care hospitals and a home care program in a mid-size Canadian city. Multiple
      sources of information were obtained to evaluate the service. Hospital emergency
      department records and home care records were reviewed. Patients who participated
      in the service (n = 96) and physicians and nurses (n = 119) who had involvement
      with the service were surveyed appraising the service in terms of relevance,
      access, quality and coordination. Study results revealed that elderly women with
      multiple health problems who lived alone were the most frequent users of the
      service. The majority of the patients admitted to the service presented with
      problems of a functional nature that were the result of a fall or mobility
      problems. The results indicated that the service did avert hospital admissions
      and facilitated a process by which patients could avoid the intermediate step of
      hospitalization before placed in a higher level of care or returning to previous
      levels of functioning. Economic analysis indicated that the value of the service
      stemmed from the benefits to patients and caregivers rather than from cost
      savings offered to acute care hospitals.

PMID- 9526725
TI  - Roles of community organizations in improving cancer prevention instruction in
      schools.
AB  - Health education can be an important factor in the development of appropriate
      health behaviors in children. Community agencies that have not traditionally
      supported school health education can be of significant influence in improving
      school health education. This study examined the relationships between the
      involvement of the American Cancer Society (ACS) in schools and the degree of
      implementation of cancer prevention curricula. School health specialists from 41
      metropolitan school districts in Texas were surveyed regarding the coverage of
      topical areas related to cancer prevention, health instructional patterns in
      districts, and collaborative efforts with the ACS. Tobacco use was widely covered
      in all levels of schools (elementary, middle, and high school), as was nutrition.
      Cancer detection and the concepts of cancer as a disease received most extensive
      coverage in high schools, and there were no significant grade level differences
      regarding coverage of the risks of sun exposure. School personnel had little
      training and felt little district support for school health education. Most
      respondents felt that teachers saw the ACS primarily as a resource for cancer
      information and resources than as a collaborative partner in health education
      efforts. Community organizations can play three roles in supporting school health
      education. First, the organization must certainly provide disease-specific
      information (in this case, cancer). They must also promote comprehensive school
      health education in general. Lastly, the study illustrates that community
      organizations must act as advocates for broader change in schools by supporting
      the development of organizational capacity within schools and districts to
      implement quality school health education, enlisting community support for
      quality school health education, and supporting policy initiatives that
      strengthen school health education activities.

PMID- 9526726
TI  - Problems in search of solutions: health and Canadian aboriginals.
AB  - The purpose of this paper is to explore the health status of Canadian
      Aboriginals, along with their perceived community health problems and proposed
      solutions to these issues. Data are drawn from the 1991 Aboriginal Peoples Survey
      (APS), which is a weighted random sample of the Aboriginal population.
      Comparisons were made with respect to group identity (North American Indian,
      Metis and Inuit) and geographic location (reserve, urban, rural and North) and
      across a series of health status and health care use indicators. Analysis reveals
      that geographic location, as compared with Aboriginal identity, appears to have a
      large impact with respect to health status and use of physician services. On
      reserve Aboriginals, for example, reported a lower likelihood of having seen a
      physician and were more likely to rank their health as fair or poor. Location
      also influenced perceived community health problems and solutions. Self
      identified problems included drugs, cancer and arthritis, while corresponding
      solutions included education, counseling and service access. Although the
      problems and solutions were relatively consistent across space, they too varied
      in their importance. In general, the results tend to reinforce the determinants
      of health framework, suggesting that the provision of health services is
      insufficient to remove health disparities on its own. Instead, broader social
      welfare provisions must be considered.

PMID- 9526727
TI  - Consanguineous marriage in an urban area of Saudi Arabia: rates and adverse
      health effects on the offspring.
AB  - The objective of this cross-sectional study was to determine the pattern and time
      trend of consanguineous marriage and its adverse health effects on the offspring
      in Dammam city, Eastern Province, in the Kingdom of Saudi Arabia. This city is
      known to attract Saudis from different parts of the country because it is in the
      heart of this industrial region. Five primary health care centers were randomly
      selected from different sectors of the city in addition to the city's only
      Maternity and Children's Hospital. For inclusion in the study a wife must have at
      least one pregnancy that terminated in either full term liveborn baby, still
      birth, or abortion. A total of 1307 ever-married Saudis completed a pre
      structured questionnaire during an interview. The rate of consanguineous marriage
      was 52.0% with an average inbreeding coefficient of 0.0312. First-cousin
      marriages were the commonest (39.3%) of all matings. The consanguineous groups
      had a significantly higher number of pregnancies. The mean birth weight of the
      offspring of consanguineous couples was not statistically significant being less
      than that of the non-consanguineous. However, within the consanguineous groups
      the more closely related couples had smaller babies on average. No significant
      differences were noted for the rates of inherited diseases and reproductive
      wastage. The rate of consanguineous marriage in this city was high and so was the
      inbreeding coefficient. These figures place this nation among the countries with
      a high rate of consanguineous marriages. A nationwide study to determine
      accurately the relationship between consanguinity and inherited diseases has much
      to commend it.

PMID- 9526728
TI  - So-called calcifying odontogenic cyst: review and discussion on the terminology
      and classification.
AB  - The so-called calcifying odontogenic cyst (COC) shows extensive diversity in its
      clinico-histopathological appearances and biological behaviour. Because of this
      diversity, there has been confusion and disagreement on the terminology and
      classification of this lesion. The attempts at classification of COC may be
      divided into two concepts. The first concept is the "monistic" one that all COCs
      are neoplastic in nature, even though the majority are cystic in architecture and
      appear to be non-neoplastic. The second is the "dualistic" concept that COC
      contains two entities: a cyst and a neoplasm. Although the World Health
      Organization (WHO) classified COC as an odontogenic tumour in 1992 based on the
      former concept, current thinking favors strongly the latter one. In this article,
      several previous classifications of COC in the literature are discussed and a new
      simple classification scheme based on the "dualistic" concept is proposed.

PMID- 9526729
TI  - Experimental odontogenic cysts induced by in vitro 4-nitroquinoline 1-oxide
      (4NQO) treatment of F344 rat incisor tooth germs.
AB  - This study was designed to establish an experimental animal model for elucidating
      the early stages of odontogenic cysts and tumors. It involves the in vitro
      treatment of tooth germs with 4-nitroquinoline 1-oxide (4NQO) at the early bell
      stage and their subsequent transplantation into the kidney subcapsular space.
      While all tooth germ transplants of the control group not exposed to the
      carcinogen showed continued tooth development with no pathological lesions, 21 of
      23 4NQO-treated tooth germs developed into similar appearing keratinized cysts
      with or without associated tooth structures. The remaining two transplants failed
      to develop cysts and formed only a tooth. The present experimental procedure was
      effective in inducing keratinized cystic lesions that exhibit some similarities
      to human odontogenic keratocysts or primordial cysts.

PMID- 9526730
TI  - Assessment of growth potential by MIB-1 immunohistochemistry in ameloblastic
      fibroma and related lesions of the jaws compared with ameloblastic fibrosarcoma.
AB  - Specimens from two ameloblastic fibromas (including one recurrent case), two
      ameloblastic fibro-odontomas, and one ameloblastic fibrosarcoma were subjected to
      investigation by MIB-1 immunohistochemistry in order to elucidate the growth
      potential of these tumors. MIB-1 labeling indices in the epithelial component of
      these tumors ranged from 2.9 to 7.5%, whereas those in the mesenchymal component
      ranged from 1.5 to 13.5%. Of these, labeling indices in the mesenchymal component
      of the recurrent ameloblastic fibroma and ameloblastic fibrosarcoma were quite
      high. These findings suggest that evaluation of growth potential in ameloblastic
      fibroma and related lesions could be of help in understanding tumor
      aggressiveness and in selecting appropriate surgical procedures.

PMID- 9526731
TI  - Proliferative activity in peripheral ossifying fibroma and ossifying fibroma.
AB  - A proliferative activity study analysing morphometric and quantitative aspects of
      nucleolar organizer regions (NORs) and proliferating cell nuclear antigen (PCNA)
      expression was conducted in 10 cases of peripheral ossifying fibroma (POF) and 10
      cases of ossifying fibroma (OF). For NOR identification, the silver staining
      technique (AgNOR technique) was used. PCNA expression was determined by
      immunohistochemical staining using the PC10 antibody. The AgNOR analysis for the
      two lesions showed a profile characteristic of benign lesions. OF showed higher
      AgNOR number and PCNA expression than POF. Our results suggest increased
      proliferative activity in OF compared with POF.

PMID- 9526732
TI  - Cytotoxic and non-genotoxic effects of arecoline on human buccal fibroblasts in
      vitro.
AB  - Betel quid chewing has been linked to oral submucous fibrosis and oral cancer.
      Cytotoxicity and genotoxicity assays were used to investigate the pathobiological
      effects of arecoline on cultured human buccal fibroblasts. Arecoline increased
      double-stranded polynucleic acid at the concentration of 0.1 to 10 micrograms/ml
      in a concentration-dependent manner. At a concentration higher than 50
      micrograms/ml, arecoline was cytotoxic to cultured fibroblasts and the
      cytotoxicity was dose-dependent. No genotoxicity for arecoline was found even at
      a concentration of 400 micrograms/ml. On the other hand, 600 micrograms/ml
      glutathione (GSH) and 200 micrograms/ml glycyrrhizin could prevent the arecoline
      induced cytotoxicity. These results indicate that arecoline is a cytotoxic agent
      and no genotoxicity was found to human buccal fibroblasts. Furthermore,
      increasing consumption of GSH- and glycyrrhizin-rich foods may reduce the oral
      diseases associated with betel quid chewing.

PMID- 9526733
TI  - p53 aberrations in oral submucous fibrosis and oral squamous cell carcinoma
      detected by immunocytochemistry and PCR-SSCP.
AB  - An archival series of oral biopsies from Karachi, Pakistan, consisting of 21
      cases of oral submucous fibrosis (OSF) and 27 cases of squamous cell carcinoma
      (SCC), of which 6 had arisen from OSF, were used to examine the aberrations in
      the structure and expression of the p53 tumour suppressor gene. The PCR-SSCP
      method was used for mutation analysis of exons 2-9, and (over)expression of p53
      protein was detected by immunocytochemistry using monoclonal antibody DO 7.
      Positive immunostaining was observed in 15/20 (75%) of OSF specimens, 3/6 (50%)
      of SCC arising from OSF and 14/21 (67%) of SCC not arising from OSF. Mobility
      shifts in SSCP indicative of a mutation in p53 or loss of heterozygosity
      (deletion of a band) were seen in 13/21 cases of OSF and 15/27 cases of SCC.
      There was concordance between immunocytochemistry and SSCP results in a majority
      (33/48) of samples. Though the number of analysed SCC cases arising from OSF was
      limited, the results suggest that p53 mutation/protein stabilisation may play a
      part in the pathogenesis of OSF and its progression to SCC.

PMID- 9526735
TI  - Cytomorphometric analysis of squames obtained from normal oral mucosa and lesions
      of oral leukoplakia and squamous cell carcinoma.
AB  - Cell and nuclear diameters (CD and ND) were measured in squames obtained from
      normal buccal mucosa and lesions of oral leukoplakia and squamous carcinoma (SCC)
      also from buccal mucosa. The study groups consisted of Group 1: normal buccal
      mucosa (n = 40); Group 2: lesions with no epithelial dysplasia (n = 58); Group 3:
      lesions with epithelial dysplasia (n = 27); and Group 4: SCC lesions (n = 51).
      The mean CD and ND values were: Group 1: 51.78 (+/- 0.11) and 8.36 (+/- 0.49);
      Group 2: 45.73 (+/- 0.16) and 8.31 (+/- 0.68); Group 3: 41.32 (+/- 0.13) and 9.04
      (+/- 0.46); Group 4: 38.58 (+/- 0.11) and 10.10 (+/- 0.56) microns, respectively.
      Correlation between the ND and CD was positive for Group 1 (r = 0.78, P < 0.05)
      and Group 2 (r = 0.33, P < 0.05). There were no significant correlations in
      Groups 3 and 4. ANOVA showed significant differences (P < 0.05) for CD between
      all four groups. Except between Groups 1 and 2, the ND was significantly
      different (P < 0.05) between all groups. The results indicate that ND and CD
      could possibly be sensitive parameters in the diagnosis of oral premalignant and
      malignant lesions.

PMID- 9526734
TI  - Epstein-Barr virus in tobacco-induced oral cancers and oral lesions in patients
      from India.
AB  - We examined 103 oral squamous cell carcinomas (OSCC), 100 oral lesions consisting
      primarily of leukoplakia (82 cases), and 76 clinically normal mucosa specimens
      from the contralateral site in the oral cavity of individuals with oral lesions,
      for the presence of Epstein-Barr virus (EBV). Polymerase chain reaction (PCR) was
      used to amplify a 239 bp fragment of the BamHIL region of the EBV genome,
      followed by Southern blot hybridization with EBV oligonucleotide probe to
      increase further the specificity and sensitivity of the assay system. Since EBV
      seropositivity is frequent in populations, we also examined the peripheral blood
      cells (PBC) from 141 patients (50 oral cancer patients, 91 patients with oral
      lesions) for the presence of EBV. We detected EBV in 25 of 103 (25%) OSCC, 13 of
      100 (13%) oral lesions, 3 of 76 (4%) clinically normal mucosa samples and 10 of
      141 (7%) PBC. Our results indicate that EBV may contribute as one of the multiple
      factors in oral cancers, in a certain proportion of Indian patients.

PMID- 9526737
TI  - [Perinatal surgery and perinatal treatment].
AB  - Recent results of neonatal surgery in Japan are presented. Nowadays, babies born
      with esophageal atresia, diaphragmatic and abdominal wall defects (gastroschisis
      and amphalocele) require special intensive surgical care after delivery, while
      those with imperforate anus, hirschoprung's disease and intestinal atresia will
      follow a relatively smooth postoperative course. Prenatal surgery or treatment
      may be necessary for some fetuses with congenital diaphragmatic hernia and
      congenital cystic adenomatoid malformation of the lung. Experiences at the
      authors institutions were reported, and recent results at institutions in the
      united states are introduced.

PMID- 9526738
TI  - [Current status of antenatal diagnosis & perinatal medical network].
AB  - Antenatal diagnosis has undergone an explosion of growth in the last decade. This
      has revolutionized the practice of fetal medicine. Ideally, the antenatal
      diagnosis of congenital anomalies should improve antenatal counseling, it may
      also affect the timing, site, and method of delivery and potentially allow for
      intrauterine surgical correction. Paradoxically worse outcomes, however, have
      been observed in cases of some anomalies such as diaphragmatic hernia and
      omphalocele. Most of them combined premature birth and/or low birth weight with
      associated lethal anomalies: the combination almost inevitably led to mortality.
      In order to reduce the mortality, new approaches will be required for such
      anomalies in the future. Perinatal medical network will also be important to
      promote a closer association between perinatal medicine and perinatal surgery.

PMID- 9526736
TI  - Histological effects and predictive biomarkers of TPP induction chemotherapy for
      oral carcinoma.
AB  - The effects of an induction chemotherapy with THP-adriamycin, cisplatin, and
      peplomycin (TPP) were studied in 32 patients with operable oral cancer. The
      histological evaluation according to the Shimozato-Oboshi classification was
      Grade (G) IV in ten cases (31.3%), GIII in one case, and GIIb in four cases.
      Induction of apoptosis and differentiation-inducing effects, hyperkeratinization
      or bone formation, were observed in some cases. The overall clinical response
      rate and histological response rate were 63% and 47%, respectively. Grade III was
      obtained in seven metastatic lymph nodes of three patients. The expressions of
      PCNA, p53, and AgNORs before and after chemotherapy were studied. The
      prechemotherapeutic PCNA positive cell index (PI) of the highly responsive tumors
      (GIII, IV) was significantly lower than that of the poorly responsive tumors (G0
      IIb) (P < 0.01). Similar results were obtained in the evaluation of p53 PI (P <
      0.05), suggesting that PCNA and p53 are useful biomarkers for predicting the
      efficacy of TPP chemotherapy.

PMID- 9526739
TI  - [Development of extracorporeal membrane oxygenation for neonates with severe
      respiratory failure].
AB  - Extracorporeal membrane oxygenation (ECMO) is one of the most highly developed
      artificial organ treatment of the last decade. Especially for severe neonatal
      respiratory failure, ECMO has become standard treatment in Japan following the
      same pattern as in the USA. In the USA, more than 12,000 infants have been
      registered for ECMO treatment by the Extracorporeal Life Support Organization
      (ELSO), and their total survival rate is above 80%. Recently, to avoid ligating
      the carotid artery, most neonates who required ECMO have been supported by a veno
      venous (V-V) bypass using a double-lumen catheter via the right internal jugular
      vein into the right atrium. To prevent bleeding complications, the introduction
      of Nafamostat Mesilate and the development of a heparin-coated system would be
      advantageous. Progresses in these instruments and perfusing techniques might
      enlarge the indications of ECMO. We performed an experiment on fetus ECMO as
      artificial placenta. The fetuses were incubated for 10-237 hours by A-V ECMO
      using a centrifugal pump successfully and maturation of the lung was revealed. In
      the future the fetus ECMO could be introduced clinically as a back-up system for
      fetal surgeries and incubation for extra-premature infants.

PMID- 9526741
TI  - [Therapeutic strategy and clinical outcome in congenital diaphragmatic hernia].
AB  - Congenital diaphragmatic hernia (CDH) continues to carry a high mortality rate
      40%-60% mainly due to severe pulmonary hypoplasia. At our institute, thirty-seven
      neonates were treated for CDH diagnosed within the first 24 hours of life. Eleven
      of thirty-seven patients died and the mortality rate was 30%. Deaths in ten
      patients were due to severe pulmonary hypoplasia. The other one patient died from
      barotrauma at three months of age. All twenty-six patients who responded to
      ventilatory management and pharmacological therapies underwent surgical repair of
      CDH and all except one survived. Eight of eleven patients who did not respond to
      treatment also underwent surgery, but all died. These cases were all treated
      fufore ECMO introduction. Two of the other three in whom ECMO support was
      instituted died postoperatively. Among the parameters PH < 7, PaO2 < 60, PaCO2 >
      60, AaDO2 > or = 600 and OI > or = 40 recorded on admission and examined
      retrospectively, OI > or = 40 was the most reliable as a predictor for poor
      outcome (sensitivity: 100%, specificity: 81%) and probably entry criteria for
      ECMO. The mean lung/body weight ratio of nonsurviving neonatal cases was as low
      as 0.49 +/- 0.18% while at least 1% is the critical value for survival. To
      salvage the CDH patient with severe pulmonary hypoplasia, surgical intervention
      before birth is inevitably necessary based on accurate prenatal diagnosis and
      established surgical techniques.

PMID- 9526740
TI  - [Improving surgical results for cardiovascular anomalies in neonates].
AB  - The surgical results for congenital cardiovascular anomalies in neonates between
      August 1987 and July 1997 were reviewed. Two hundred thirty-four neonates
      underwent the corrective surgery with the use of cardiopulmonary bypass (CPB) for
      the cardiac anomalies including transposition of the great arteries (d-TGA) (157
      patients), total anomalous pulmonary venous connection (TAPVC) (44 patients),
      cardiac defects with the aortic arch anomalies (11 patients), and others (22
      patients), with an early mortality rate of 12%. The survival rates through the
      arterial switch operation for d-TGA and correction for TAPVC in 30 days were
      satisfactory (92% and 89%, respectively). The early mortality rate of palliative
      surgery done without CPB in 115 neonates due to aortic arch anomalies, pulmonary
      outflow tract obstruction, or pulmonary hypertension was low (6%). In contrast
      with these results, the outcome of palliative surgery using CPB for hypoplastic
      left heart syndrome, the aortic arch anomalies with subaortic stenosis, or TAPVC
      in asplenia hearts was poor, with the surgical mortality of 80%.

PMID- 9526742
TI  - [Recent advance in the treatment of congenital esophageal atresia and congenital
      tracheal stenosis].
AB  - Advances in anesthetic management, neonatal intensive care and cardiovascular
      techniques for severe cardiac defects have permitted improved survival rate for
      esophageal atresia (EA) and/or tracheoesophageal fistula (TEF) during the last
      two decades. In the treatment of EA-TEF, primary esophageal repair without
      staging or preliminary gastrostomy becomes popular among pediatric surgeons. In
      pure EA and long-gap EA with TEF, options for esophageal reconstruction include
      use of the native esophagus or replacement with colon or stomach. In considering
      the esophageal motility in patient's whole life, native esophageal reconstruction
      is the procedure of choice rather than esophageal replacement. Improved survival
      rates are noted irrespective of the traditional Waterson criteria, which now seem
      outdated. The surgical treatment of congenital tracheal stenosis have started in
      the early '80s. Resection of the stenotic trachea with end-to-end anastomosis has
      been available in the stenosis ranging less than 30% of the entire trachea.
      However, the treatment of long segment tracheal stenosis is still controvertial.
      Various surgical techniques including balloon tracheal split, slide
      tracheoplasty, implantation of autografts of pericardium and costal cartilage
      have been attempted. In this review, we described our own experience in
      tracheoplasty using costal cartilage.

PMID- 9526743
TI  - [Current status of management of omphalocele and gastroschisis].
AB  - Forty-five cases of gastroschisis and 85 of omphalocele were reviewed. The
      survival of gastroschisis has dramatically improved over the past 20 years,
      however, that of omphalocele still remained in the lower value, because the size
      of the defect and the presence of associated anomalies are prognostic factors.
      The primary fascial closure was first employed for the patients with
      gastroschisis and a silo chimney was used for limited cases. On the other hand,
      for the patients with omphalocele, primary closure was possible in 34 cases, silo
      chimney was used in 17, and 45 cases had nonoperative management with
      epithelialization. Among them, nonoperative management using painting was the
      most reliable therapeutic for omphalocele.

PMID- 9526744
TI  - [Congenital atresia and stenosis of the intestine].
AB  - During the period between 1946 and 1996, 59 patients of intrinsic duodenal
      obstruction and 67 of intrinsic jejunoileal obstruction were treated in our
      institute. Analysis of data obtained from the patients revealed that the duodenal
      obstruction was the most successfully treated by diamond-shaped
      duodenoduodenostomy, jejunal obstruction by resection of the dilated oral blind
      end, tapering jejunoplasty and ileal obstruction by resection of the dilated
      blind end and anastomosis or ileostomy in case with peritonitis. Associated
      anomalies in duodenal obstruction, anastomotic malfunction and postoperative
      short bowel syndrome in jejunal obstruction and complicated peritonitis in ileal
      obstruction were the most effective as prognostic factors.

PMID- 9526745
TI  - [Management of anorectal malformations and Hirschsprung's disease].
AB  - Anorectal malformations include various type of anomalies resulting from abnormal
      development of hindgut, allantois and Mullerian duct. It is essential for the
      successful construction of new anorectum to know the correct anatomy of pelvic
      muscles. Pena and deVries proposed a new concept of pelvic muscles, the surgical
      entities "muscle complex". Based on new anatomical understanding, posterior
      sagittal anorectoplasty (PSARP) was described by Pena and deVries and has gained
      a wide acceptance in the world. This approach may lead us a better understanding
      of surgical anatomy and change our therapeutic concept. Hirschsprung's disease is
      known to be congenital disorder characterized by the absence of enteric nervous
      system. Recently, gene mutations associated with Hirschsprung's disease have been
      widely investigated and gene mutations of RET, glial cell line-derived neutrophic
      factor (GDNF), endothelin receptor B (EDNRB) and endothelin-3 (EDN3) have been
      identified in patients with Hirschsprung's disease. These results suggest a role
      of gene mutations in the migration and differentiations of neural crest-derived
      neuroblasts. One-stage endorectal pull-through procedure in the neonate and a
      primary laparoscopic pull-through procedure has been shown to be feasible.

PMID- 9526746
TI  - [Heart and lung surgery 86-96].
AB  - During a period between April 1, 1986 and December 31, 1996, a total of 3190
      cardiothoracic operations were performed in our Department. The overall mortality
      was 4.1% The prerequisite for successful accomplishment of clinical research was
      discussed in detail.

PMID- 9526747
TI  - [12th World AIDS Conference announces call for abstracts--Geneva to host world's
      foremost AIDS Conference; focus on "bridging the gap"].

PMID- 9526748
TI  - Pressure algometry in healthy subjects: inter-examiner variability.
AB  - The purpose of this study was to estimate inter-examiner reliability of head and
      neck algometry. Pain perception thresholds were assessed with a mechanical
      pressure algometer in 21 healthy individuals. Thresholds were assessed at 13
      symmetrical points on each side of the head and neck, at the deltoid muscle and
      at the median finger. The pressure range of the instrument proved insufficient to
      study the pain perception threshold on the finger, however. Two different
      examiners carried out one or two examinations in each subject during one day. The
      sequence of investigations was varied randomly. The inter-examiner reliability
      was found to be good, with a mean intra-class correlation coefficient (ICC) of
      0.75. Intra-examiner reproducibility was excellent (mean ICC = 0.84). The mean
      inter-examiner coefficient of variation was 18.7%, while the mean coefficient of
      repeatability (CR) was 1.60 kg/cm2. In comparison, the mean intra-examiner
      coefficient of variation was 15% while the mean CR was 1.29 kg/cm2. Statistically
      significant differences between examiners were found for the frontal point (p <
      0.01), while a trend towards lower thresholds in one of the two observers was
      seen in 10 of the 13 non-significant points. Inter-examiner reliability of side
      differences was excellent, with CR = 1.23 kg/cm2. In conclusion, manual algometry
      with a rather inexpensive mechanical device has a good to excellent inter-rater
      reliability. When studying patients, however, the possible bias introduced by
      different examiners should be taken into account, both regarding study design and
      data analysis.

PMID- 9526750
TI  - An evaluation of multidisciplinary intervention governed by functional
      independence measure (FIMSM) in incontinent stroke patients.
AB  - Patients with acute hemispheric stroke and ensuring urinary incontinence were
      randomly allocated to a ward using conventional methods of rehabilitation (n =
      13) or to a ward practicing rehabilitation governed by Functional Independence
      Measure (FIM) (n = 21). All patients were assessed on admission and on discharge
      using the Katz activities of daily living (ADL) index, the psychological general
      well-being index, item G of the FIM index (FIM-G), and a mobility score. Patients
      admitted to the ward utilizing FIM were additionally evaluated using the total
      FIM on admission, repeatedly during the rehabilitation period and on discharge.
      An individual rehabilitation programme based on the latest FIM score was used
      throughout rehabilitation. There were no differences on admission between groups
      regarding clinical and demographic characteristics, ADL, mobility and mood.
      Twenty patients in the intervention group regained continence before discharge
      compared to 3 (p < 0.01) in the control group. There was also a greater
      improvement in well-being in the intervention group compared to the control group
      (p < 0.01). This study has indicated that rehabilitation governed by the use of
      FIM reduced urinary incontinence and enhanced well-being better than conventional
      methods of rehabilitation. The results warrant a larger study to further
      investigate rehabilitation of incontinent stroke patients using FIM.

PMID- 9526749
TI  - Postural asymmetry reduction by vestibular caloric stimulation in left
      hemiparetic patients.
AB  - The purpose of this study was to investigate the effects of caloric vestibular
      stimulation on the postural sway characteristics of hemiparetic patients. Two
      groups of 15 hemiparetic patients each (right and left) were compared to a group
      of 15 control subjects. Hemiplegic patients were selected for the study if they
      showed ability to stand without external support for at least 30 seconds.
      Posturographic evaluation was performed on a statokinesimetric platform just
      before and after a cold contralesional ear irrigation (20 degrees C) during 60
      seconds. Two quantitative parameters were analysed: the antero-posterior
      difference and the lateral difference, reflecting the asymmetry of standing in
      the antero-posterior and frontal planes, respectively. The results of the 3
      groups studied were compared with a Student's t-test. Before stimulation, as
      previously reported, left hemiparetic patients showed a predominant lateral
      displacement of the centre of pressure toward the side of the lesion, as compared
      to right hemiparetic patients. After vestibular stimulation, the lateral
      displacement was reduced in both patient groups, predominantly in the left
      hemiparetic group. After vestibular stimulation, the lateral displacement thus
      was not different in both patient groups and in the control group. Antero
      posterior differences were not significantly different in the patient groups and
      in the control group before stimulation and were not affected by vestibular
      stimulation. The suggestion is made that greatest postural imbalance produced by
      right brain damage could reflect a persistent distorsion of a "spatial postural
      representation". Vestibular stimulation may restore symmetrical activity in the
      cerebral structures involved in the generation of this "spatial postural
      representation".

PMID- 9526751
TI  - Life satisfaction of persons with spinal cord injury compared to a population
      group.
AB  - Life satisfaction is thought to be the subjective part of quality of life, i.e.
      the feelings of the persons concerned about their functioning and circumstances.
      In this study, life satisfaction of spinal cord-injured persons living in the
      community is compared to life satisfaction of a population group. Respondents
      were a nationwide sample of 318 persons with spinal cord injury (response 60%)
      and 507 inhabitants of a large city in The Netherlands (response 42%). Life
      satisfaction was measured using the Life Satisfaction Questionnaire, containing
      one question about general life satisfaction and eight questions about domain
      specific life satisfaction. Mean scores of general life satisfaction and of
      satisfaction with self-care ability, leisure situation, vocational situation and
      sexual life were lower in persons with spinal cord injury than in the population
      group, but satisfaction with family life was higher. However, differences in
      general life satisfaction, satisfaction with leisure situation and with
      vocational situation could be attributed to differences in the composition of
      both groups. Satisfaction with self-care ability was lower in persons with
      tetraplegia than in persons with paraplegia, but we found no differences in other
      questions. Several relationships between life satisfaction and age and marital
      status existed, but they were more pronounced in the population group than in the
      group of persons with spinal cord injury. Time after injury and cause of injury
      were not related to life satisfaction variables. Uniformity in measurement
      instruments would facilitate comparisons between studies.

PMID- 9526752
TI  - Interdisciplinary rehabilitation of hospital employees with musculoskeletal
      disorders.
AB  - At Lund University Hospital a cooperation project started in 1989 between the
      Rehabilitation Clinic and the Occupational Health Service Unit for the
      rehabilitation of 34 hospital employees with musculoskeletal problems and a
      median sick-listing time of 6 months, treated as day-patients by an
      interdisciplinary team. Evaluation instruments used were the Nottingham Health
      Profile (NHP), Pain Drawing, Visual Analogue Scale for pain, and the Disability
      Rating Index (DRI). The most prominent immediate effect was a significant
      increase of perceived energy and significant improvement of the total score of
      health-related quality of life (NHP). After 12 months, 25 out of 34 (74%)
      subjects had returned to work. The reference group used consisted of 57 subjects
      referred earlier from the Occupational Health Service Unit to the Personnel
      Department, for vocational rehabilitation. The groups were followed by 2-4 years
      using questionnaires concerning working conditions and current health status.
      There was a significant difference (p = 0.038) in return to work: intervention
      group 77%, reference group 58%.

PMID- 9526753
TI  - The role of ankle plantar flexor muscle work during walking.
AB  - Impaired ankle plantar flexor (APF) function is a frequent cause of gait
      limitations, but the role of the APF in the forward propulsion of the body
      remains controversial. To better understand both the direct and indirect effects
      of the APF during push-off and through advancement of the leg, mechanical work
      and inverse dynamic analyses were performed on 8 normal subjects during level
      walking. During push-off, 23.1 joules (J) of energy were generated, primarily by
      the APF, but only 4.2 J of this energy is transferred into the trunk. Ankle
      plantar flexor work is primarily used to accelerate the leg into swing. Most of
      the energy, 18.6 J, is recovered by transfer into the trunk at the end of swing.
      The timing of the energy transfers relative to the trunk motion imply that the
      APF contributes to the forward kinetic energy of the trunk but that other
      mechanisms likely account for the work used to raise the trunk against gravity.

PMID- 9526754
TI  - Repeated maximum reciprocal knee movements in patients with minimal overt
      symptoms after ischaemic stroke: an evaluation of mechanical performance and EMG.
AB  - The ability to perform reciprocal knee flexions and knee extensions was
      investigated in patients with minimal or no overt motor symptoms after stroke.
      Ten patients and 22 controls performed 10 maximal reciprocal knee extensions and
      knee flexions without intervening rest period using an isokinetic dynamometer
      (Cybex II). Peak torque (PT; Nm), signal amplitude (RMS) and mean frequency
      (fmean) of the electromyography were registered for each extension and flexion
      separately and as the ratio extension/flexion. The patients exhibited pronounced
      motor deficit despite no or minimal overt clinical symptoms. The reduced motor
      capacity in the knee muscles was shown as a decrease in the PT and in a different
      electromyographic pattern compared with the controls. A bilateral affection was
      found with the formerly hemiparetic side mostly affected. Repeated reciprocal
      contractions influenced the motor performance, shown as an increase of the PT
      ratio in the patients, which was especially pronounced with an increasing number
      of contractions.

PMID- 9526755
TI  - The process of vocational rehabilitation for employed and unemployed people on
      sick-leave: employed people vs unemployed people in Stockholm compared with
      circumstances in rural Jamtland, Sweden.
AB  - The likelihood that a period of sick-leave will result in a temporary disability
      pension is about three times greater for unemployed people than for those with
      jobs. The aim of this study was 1) to compare the vocational rehabilitation of
      the employed with the rehabilitation of the unemployed in the city of Stockholm
      and 2) to compare the results with previous results from rural Jamtland. The
      study was based on 156 matched cases on long-term sick-leave (90 days or more)
      initiated during 1992 and 1993. Two inclusion criteria were that the diagnoses
      should indicate low-back pain or problems in the neck/shoulders, and that the
      patients should be below 58 years of age. Our hypothesis was that the unemployed
      were disregarded in vocational rehabilitation. The results confirm this in that
      rehabilitation plans are not established to the same extent for the unemployed as
      for the employed. Against our hypothesis, however, no difference exists in
      rehabilitation impulse, rehabilitation investigation or rehabilitation measures
      received. The major finding of the study is, instead, that rehabilitation in
      general seems beset with problems. Rehabilitation activities seem far too few and
      initiated unnecessarily late. Neither the employers nor the social insurance
      offices seem to be fulfilling their statutory duties. The results of the study
      correspond well with the results previously found in rural Jamtland.

PMID- 9526756
TI  - Importance and attainment of life values among disabled and non-disabled people.

PMID- 9526757
TI  - Restricting the influx of disability beneficiaries by means of law: experiences
      in Norway.
AB  - OBJECTIVES: To study effects of restricting eligibility criteria for disability
      pension in Norway 1991. METHODS: Documents of 288 applicants from 1990 and 1993
      in one county were analysed for social and medical variables as well as for the
      determination and its causes. RESULTS: Incidence of applications for disability
      benefits during a three-month period was 223 per 100,000 inhabitants in 1990. The
      focused group of 'medically imprecise' musculoskeletal diagnoses concerned 26% of
      all applicants, while 'precise' musculoskeletal diagnoses were given to 15%,
      'imprecise' psychiatric diagnoses to 7% and 'precise' ones to 6%. The number of
      applicants fell by 39%, surprisingly about the same in all social and diagnostic
      groups. Denial rate increased from 8% to 21%. Denials mostly struck women, middle
      aged, those living alone, those with short education, and applicants with
      'medically imprecise' diagnoses. CONCLUSIONS: Restriction of disability benefits
      affected applicants with the least resources the hardest, and seems to contribute
      to the on-going process of marginalizing the weaker part of the population.

PMID- 9526758
TI  - Homicide and suicide in Swedish counties.

PMID- 9526760
TI  - Political violence, family stress and mental health of refugee children in exile.
AB  - The mental health of 63 refugee children, with a mean age of 5.9 years, from
      Chile and the Middle East, were studied during the first 18 months of exile in
      Stockholm, Sweden. 46% of the children were rated as having poor mental health
      five months after resettlement in symptom interviews with parents based on the
      structured questionnaire developed by Cederblad, and 44% thirteen months later.
      Political violence in the home country and stress in the family sphere in exile
      were identified as the major determinants of poor mental health in this context.

PMID- 9526759
TI  - Low birth weight in China and Finland.
AB  - Although a developing country, China has a lower occurrence of low birth weight
      (LBW) than many developed countries. This study of two population-based one-year
      birth cohorts, from Finland in 1985-86 and China in 1992, shows the occurrence of
      low birth weight (LBW) (1000- < 2500 g) among singletons to be 2.6 percent in the
      Chinese cohort and 3.0 percent in the Finnish one, and that of preterm births (28
      < 37 weeks) 2.7 percent and 4.5 percent, respectively. The main component of LBW
      is term LBW (57.4 percent) in the Chinese case and preterm LBW (64.7 percent) in
      the Finnish case. The perinatal mortality rate (PMR) was twice as high in the
      Chinese cohort (13.0 vs. 5.9 per thousand). The occurrence of LBW in the Finnish
      cohort decreased to 2.3 percent after crosstabulation of the Finnish mothers to
      conform in structure to the population of Chinese mothers in terms of maternal
      age, marital status and maternal smoking. The result suggests that the lower
      incidence of LBW in the Chinese cohort seems to be a reflection of the Chinese
      socio-cultural environment, which provides Chinese mothers with favourable
      characteristics. The Finnish excess LBW would have disappeared if the mothers had
      possessed those characteristics as well. The excess perinatal deaths in the
      Chinese series might be explained by the different levels of perinatal health
      care in the two countries.

PMID- 9526761
TI  - Work and strain on physicians in Finland.
AB  - In this study we compared the Karasek job demand-control model with an
      alternative model in an attempt to explain strain on Finnish physicians (n = 91)
      at work. Based on previous research, job demands were studied in terms of time
      pressure and demands related to patients. LISREL (8) analysis was used to test
      the models. The three factor model, providing the most parsimonious explanation
      of the data, suggested that time pressure, patient-related stress and
      controllability all have unique predictive ability of strain on Finnish
      physicians.

PMID- 9526762
TI  - The gender gap in musculoskeletal-related long-term sickness absence in Norway.
AB  - OBJECTIVE: To examine the gender differences in long-term (> 14 days) sickness
      absence due to musculoskeletal health problems. DESIGN: Analysis of data from the
      National Sickness Benefit Register, 1994. SETTING: The economically active
      population in Norway, except civil servants (n = 1,978,030). SUBJECTS: All
      persons, 16-66 years old, with long-term sickness absence episodes due to
      musculoskeletal health problems in 1994 (n = 141,839). MAIN OUTCOME MEASURES:
      Cumulative incidence, episode frequency, and episode duration of sickness
      absence. RESULTS: Women had higher cumulative incidence of sickness absence than
      men-80.6 pr 1,000 vs. 64.1 pr 1,000, and longer mean duration of episodes-94
      calendar days vs. 86 days counted from the first day of absence. Episode
      frequency did not differ between the genders. After adjustment for age and income
      the gender ratio (men/women) in cumulative incidence changed from 0.80 to 1.08,
      and in mean duration from 0.91 to 0.96. CONCLUSION: Long-term sickness absence
      due to musculoskeletal health problems was strongly associated with gender, age,
      income, and diagnosis. Multivariate analysis indicated that the large gender
      differences in sickness absence might be overstated due to lack of adjustment for
      income and income-related factors.

PMID- 9526763
TI  - Prevalent knee pain and sport.
AB  - STUDY OBJECTIVE: To estimate the prevalence of knee pain in active athletes and
      to investigate potential associations to type, amount and duration of sports
      participation. MEASUREMENTS: 339 athletes gave information about occupation,
      sports activity and different features of knee pain, based on a self-filled
      questionnaire. MAIN RESULTS: The prevalence of knee pain within the preceding 12
      months, constant or recurrent knee pain, absence from sport and absence from work
      due to knee pain, was 54%, 34%, 19% and 4%, respectively. Knee pain was
      positively associated with years of jogging and with weekly hours of
      participation in competitive gymnastics but negatively with weekly hours of
      tennis. Constant or recurrent knee pain was positively associated with years of
      swimming. Absence from sport due to knee pain was positively associated with
      weekly hours of soccer participation. CONCLUSIONS: Knee pain is a common symptom
      in athletes. The prevalence is associated with the type, amount and duration of
      sports participation.

PMID- 9526764
TI  - Significant changes in the terminal care of aged patients in the long-term care
      in Helsinki.
AB  - Elderly patients (> or = 65 y) admitted to permanent institutional care in 1976
      (n = 116) and 1985 (n = 193) in the city of Helsinki, Finland, were analyzed
      retrospectively in order to evaluate changes in the terminal care of aged
      patients. Patients were more demented and needed more care in 1985 than 1976.
      Decisions of "do not treat actively" (= NTA) increased from 16% to 39% for all
      patients and 18% vs 42% in patients not transferred. Laboratory examinations,
      parenteral treatment as well as antibiotic treatments in febrile patients during
      the last 7 days decreased even after controlling for dementia and functioning,
      but transfers to other institutions remained unchanged. The survey demonstrates
      that the terminal care has changed significantly as recommended in the
      guidelines.

PMID- 9526766
TI  - Social consequences of substance abuse: the impact of comorbid psychiatric
      disorders. A prospective study of a nation-wide sample of treatment-seeking
      patients.
AB  - This is both a retrospective and a 16 and 28 months prospective study of the
      association between psychiatric comorbidity and social consequences (accidents,
      fights, broken relationships, drunken driving arrest, and reduced employment)
      related to alcohol in a nation-wide sample (n = 351) of substance abusers seeking
      inpatient treatment. Psychiatric comorbidity was evaluated with the Diagnostic
      Interview Schedule, while drinking history and social consequences were assessed
      with a structured questionnaire. The social consequences had a high rate of re
      occurrence. Controlled for alcohol consumption, polysubstance abuse predicted
      accidents (OR = 2.9) and fights (OR = 3.9) among men, while among pure alcoholics
      of both sexes phobia (OR = 4.3) and antisocial personality disorder (OR = 3.0)
      predicted fights. Only level of abuse predicted broken relationships. Antisocials
      had most drunken driving arrests. Attempts to reduce these social consequences
      should aim at treating polysubstance abuse, phobia, and antisocial personality
      disorder. However, the overriding aim should be the promotion of abstinence.

PMID- 9526765
TI  - Prevalence of dementia, delirium and psychiatric symptoms in various care
      settings for the elderly.
AB  - A prevalence study of psychiatric symptoms was performed in parts of a hospital
      catchment area in Mid-Sweden. In total 717 patients, aged 75 years and above, who
      were receiving care in an emergency hospital, three nursing homes, five old
      people's homes and two home medical care districts were included. All patients
      were examined using the OBS-scale (Organic Brain Syndrome Scale). Anxiety (51%),
      psychomotor slowing (45%), delirium (44%), depressed mood (41%), irritability
      (40%) and dementia (33%) were the most prevalent psychiatric symptoms or
      diagnoses in the sample but there were wide differences between the four care
      settings. The present study shows that the prevalence of dementia, delirium and
      psychiatric symptoms is high in all types of care settings for the elderly. It
      also demonstrates the need for psychiatric medical and nursing competence in all
      types of care for the elderly.

PMID- 9526767
TI  - Doping among high school students in Uppsala, Sweden: A presentation of the
      attitudes, distribution, side effects, and extent of use.
AB  - The aim of this study was to determine the extent of doping drug use among
      adolescents in Uppsala, Sweden, and to analyse the main reasons for the use. An
      anonymous multiple-choice questionnaire was distributed among pupils in the first
      and the third grades at high school; 2,742 pupils participated in the study. The
      results showed that 2.7% of the male and 0.4% of the female adolescents had used
      doping drugs at some time in their life. However, knowledge of how to get doping
      drugs far exceeded use. The main reasons for using doping drugs were to improve
      appearance and to enhance performance in sports. Some boys self-reported side
      effects of AAS. Despite the still predominantly negative attitude toward doping
      prevention programs have to be taken.

PMID- 9526768
TI  - Food frequency questionnaire versus 7-day weighed dietary record information on
      dietary fibre and fat intake in middle-aged Swedish men.
AB  - To study the magnitude of agreement between a short self-administered food
      frequency questionnaire and a 7-day weighed dietary record regarding the
      consumption of fibre and fat, we collected information from 92 randomly selected
      middle-aged Swedish men. The participants first recorded all foods and drinks
      consumed over seven consecutive days by means of a digital scale. One month after
      the 7-day weighed record had been completed, a self-administered food frequency
      questionnaire on habitual consumption of foods containing fibre or fat during the
      preceding month was sent to the subjects. The 20 largest contributors of fibre
      and fat in the diet accounted for 71% and 52% of the total intake, respectively,
      based on the 7-day weighed record. The estimated mean consumption of fibre was
      19.0 grams per day based on the 7-day weighed record and 18.3 grams per day based
      on the food frequency questionnaire. Corresponding estimated mean consumption of
      fat was 88.6 grams per day versus 46.9 grams per day. Men with high physical
      activity and low BMI, respectively, had higher intake of fibre and fat. These
      differences were seen for both dietary measurement methods but were more marked
      using the 7-day weighed record. The agreement between methods for each individual
      was also assessed. Based on five categories of fibre consumption, 61% of the
      respondents in the highest quintile according to the 7-day weighed record were
      classified in one of the two highest quintiles according to the food frequency
      questionnaire. The corresponding figure for fat intake was 56%. We conclude that
      the short self-administered food frequency questionnaire used in the present
      study can assess the absolute intake of fibre, but not of fat, with good
      precision. Also, the ranking of individuals in broad categories of consumption of
      fibre and fat was not largely misclassified based on this short questionnaire.

PMID- 9526769
TI  - Refugee children from the Middle East.
AB  - OBJECTIVE: To map the frequency (prevalence) of torture victims among parents in
      asylum seeking Middle Eastern refugee families, to map the occurrence
      (prevalence) of experiences of war and other forms of organised violence among
      the children in these families, to map the occurrence (prevalence) of emotional
      symptoms and behavioural problems among the children, and to identify risk
      indicators and modifying factors for anxiety symptoms among the children. DESIGN:
      Interview with parents using a structured interview questionnaire developed for
      this study. Validated through a blinded semi-structured interview conducted with
      approximately 1/3 of the families. AUSPICES: The study has been carried out by
      the Rehabilitation and Research Centre for Torture Victims (RCT) in cooperation
      with the Danish Red Cross. MATERIAL: Structured interviews with parents regarding
      311 children aged 3-15 from 149 families, all registered as asylum seekers from
      the Middle East between February 1, 1992 and April 30, 1993. The response was
      90.4%. PRINCIPAL VARIABLES: Background (past-past)--social and demographic data;
      trauma complex (past)--war-related life circumstances (conditions) and
      experiences of war and other forms of organized violence such as loss,
      separation, direct exposure to violence and witnessing acts of violence (specific
      events and changes of life conditions); present life context (past-present)-
      family circumstances upon arrival in Denmark; effect (present)--the child's
      current psychological state. RESULTS: 28% of the parents (44% of the fathers and
      13% of the mothers) had been tortured, to the effect that 51% of the children
      were part of a family including a survivor of torture. The most frequent specific
      types of violence-related events or circumstances were 'lived in a refugee camp
      outside the home country' (92%), 'lived under conditions of war' (89%) and 'been
      on the run with parents' (89%). Twenty percent of the children had lost one
      parent, and another 60% had been separated from one parent for more than a month.
      The highest prevalence of emotional symptoms were found within the anxiety
      dimension, as 67% of the children were assessed as being clinically anxious. The
      most important risk indicators for anxiety were 'lived in a refugee camp outside
      the home country', 'part of a torture surviving family', 'lack of opportunities
      for play with other children', 'beaten/kicked by an official', and 'loss of
      father'. Current parental behaviour was also an important risk indicator for
      anxiety, if the mother or father hit or punished the child more than was the case
      prior to arrival in Denmark. The most important anxiety-modifying factor was
      arrival in Denmark in the company of both parents. CONCLUSIONS: Asylum seeking
      refugee children from the Middle East have had many experiences of war and other
      forms of organised violence. The children frequently reacted with anxiety and
      with other symptoms of emotional instability. Prevalent anxiety symptoms
      correlated both with previous living conditions and present family situation.
      Living under prolonged conditions influenced by war and other forms of organised
      violence (prevalence) were found to a higher degree to be risk indicators for
      anxiety than were specific events or changes of life conditions (incidence).

PMID- 9526770
TI  - Preoperative evaluation and monitoring chemotherapy in patients with high-grade
      osteogenic and Ewing's sarcoma: review of current imaging modalities.
AB  - Diagnostic imaging is pivotal in the initial detection, characterization, staging
      and post-treatment follow-up of patients with high-grade osteogenic and Ewing's
      sarcoma. In the present review article, conventional and new imaging modalities
      are discussed with regard to the monitoring of the effect of neoadjuvant
      chemotherapy in such patients. Presurgical monitoring of response to chemotherapy
      may have an impact on modification of neoadjuvant treatment protocols, on patient
      selection for the performance and timing of limb-salvage surgery and on planning
      of radiation therapy (in non-operated Ewing's sarcomas) and selection of
      postoperative chemotherapy regimens. Dynamic contrast-enhanced MR imaging, as
      part of a routine MR protocol, assists in the detection of the most viable parts
      of the tumour and serves as an initial standard for follow-up of the metabolic
      activity of the tumour during and after chemotherapy, both in small intraosseous
      tumours and in tumours with an associated soft tissue mass. In combination with
      selected morphological features, dynamic imaging parameters are therefore
      advocated for monitoring the effect of neoadjuvant chemotherapy in patients with
      osteogenic and Ewing's sarcoma.

PMID- 9526772
TI  - Magnetic resonance imaging of the hip with a pelvic phased-array surface coil: a
      technical note.
AB  - OBJECTIVE: The aim of this study was to assess the capability of high-resolution
      images obtained with a commercially available pelvic phased-array surface coil to
      demonstrate normal hip anatomy. DESIGN: We retrospectively analyzed the oblique
      coronal magnetic resonance (MR) images of hips of 36 consecutive patients
      acquired on a 1.5-T clinical imager using a pelvic phased-array coil as a
      receiver, a 16-20 cm field of view, and 5 mm slice thickness. PATIENTS: Thirty
      six patients were studied, age 15-81 years. There were 20 males and 16 females.
      RESULTS AND CONCLUSIONS: The articular cartilage, cortex, superior labrum, and
      iliofemoral ligament were well visualized on proton density weighted fat
      saturation (PDF) images. The femoral and obturator vessels, obturator nerve, and
      various muscles were easily seen on T1-weighted images. High-resolution imaging
      of the hip is achievable in a reasonable amount of time using newer phased-array
      surface coils and may play an increasing role in the future evaluation of hip
      disorders.

PMID- 9526771
TI  - Skeletal metastases from breast cancer: uptake of 18F-fluoride measured with
      positron emission tomography in correlation with CT.
AB  - OBJECTIVE: To characterise the uptake of 18F in skeletal metastases from breast
      cancer using positron emission tomography (PET) and to relate these findings to
      the appearance on CT. PATIENTS AND DESIGN: PET with 18F and CT were performed in
      five patients with multiple skeletal metastases from breast cancer. The CT
      characteristics were analysed in areas with high uptake on the PET study. Dynamic
      PET imaging of the skeletal kinetics of the 18F-fluoride ion were included.
      RESULTS: The areas of abnormal high accumulation of 18F correlated well with the
      pathological appearance on CT. Lytic as well as sclerotic lesions had markedly
      higher uptake than normal bone, with a 5-10 times higher transport rate constant
      for trapping of the tracer in the metastatic lesions than in normal bone.
      CONCLUSION: PET with 18F-fluoride demonstrates very high uptake in lytic and
      sclerotic breast cancer metastases.

PMID- 9526773
TI  - Vacuum disc: frequency of high signal intensity on T2-weighted MR images.
AB  - OBJECTIVE: To determine the frequency of lumbar intervertebral disc vacuum clefts
      demonstrating high signal intensity on T2-weighted magnetic resonance (MR)
      images. DESIGN AND PATIENTS: MR images of the lumbosacral spine of 100 patients
      with radiographic evidence of the lumbar intervertebral disc vacuum phenomenon
      were retrospectively studied for the signal pattern of the intervertebral disc
      vacuum clefts. RESULTS AND CONCLUSION: Twelve of the reviewed MR studies
      demonstrated high signal intensity of the vacuum clefts on long TR and TE
      sequences while the remaining 88 cases demonstrated the vacuum as signal void on
      both T1- and T2-weighted images. It is concluded that vacuum clefts not
      infrequently show high T2 signal intensity.

PMID- 9526774
TI  - Joint fluid enhancement at MRI of the glenohumeral joint with intravenous
      injection of gadodiamide in standard and triple dose: a prospective comparative
      study of stable and unstable shoulders.
AB  - OBJECTIVE: To investigate the joint fluid enhancement at MRI of unstable and
      stable glenohumeral joints after intravenous administration of different doses of
      gadodiamide. DESIGN AND PATIENTS: Fourteen patients with unilateral anterior
      shoulder instability and six healthy controls had both shoulders examined on two
      occasions using either a standard dose (0.1 mmol/kg) or a triple dose (0.3
      mmol/kg) of gadodiamide in an open MRI magnet (0.2 T). RESULTS AND CONCLUSIONS:
      The joint fluid enhancement in the unstable shoulders was on average 134%
      following the lower dose and 182% for the triple dose, whereas corresponding
      values in the stable shoulder in the same individuals were 69% and 142%, and (65%
      and 159%) in the healthy controls. Enhancement of the joint fluid was higher
      after the triple dose than after the standard dose in both the unstable shoulders
      (P < 0.0001) and the controls (P < 0.0005). Compared with the stable controls
      enhancement in the unstable shoulders was higher for the lower dose (P < 0.0001)
      while there was no significant difference between the groups following the higher
      dose. The improved enhancement following the higher dose was especially evident
      in stable shoulders, while the lower dose was found satisfactory for unstable
      shoulders.

PMID- 9526775
TI  - A new in vivo technique for three-dimensional shoulder kinematics analysis.
AB  - OBJECTIVE: The field of shoulder kinematics research has long relied upon the use
      of cadaveric models or invasive techniques in human volunteers. In this paper, a
      novel method is presented that utilizes magnetic resonance imaging (MRI) and a
      software system called 3DVEWNIX. This method permits non-invasive, repetitive
      evaluation of living patients for glenohumeral kinematics analysis. The
      objectives of this study were twofold: to validate the quantitative accuracy of
      this technique; and to demonstrate glenohumeral relationships in asymptomatic
      volunteers during internal and external rotation of the arm. DESIGN: The
      translational accuracy was first assessed by comparing known cadaveric
      glenohumeral translations with calculations from MR images of the cadaver. Nine
      asymptomatic volunteers were subsequently placed in an external shoulder
      positioning device in the scanner and imaged in 10 degrees increments of actively
      achieved internal and external rotation. Three-dimensional reconstructions of the
      glenoid and humerus were used to evaluate the glenohumeral relationships in the
      tested positions of rotation. RESULTS: The quantitative analysis revealed an
      error of 0.61 mm (SEM 0.11 mm). Examination of the volunteers demonstrated normal
      relationships about the glenohumeral joint in internal and external rotation. In
      addition, this method provided detailed images of the bony surface architecture
      from any perspective. These images can be transformed into a cinematic three
      dimensional depiction of active shoulder rotation. CONCLUSION: This new technique
      offers an accurate, non-invasive method for assessing the normal glenohumeral
      relationships in shoulder kinematics. We now possess the capability to
      investigate the kinematics of normal and abnormal shoulder conditions non
      invasively in a large patient population.

PMID- 9526776
TI  - Osseous hemangiopericytomas of unsuspected intracranial origin.
AB  - Two cases of osseous hemangiopericytoma are presented that were initially
      diagnosed as primary in origin, but later reclassified as metastases, after a
      history of resection for an intracranial tumor was discovered. An intracranial
      source should be excluded before an isolated osseous tumor is determined to be a
      primary hemangiopericytoma.

PMID- 9526777
TI  - Carotid body paraganglioma metastatic to bone: report of two cases.
AB  - Two patients with carotid body paraganglioma developed bone metastases 3 and 6
      years respectively after surgical excision of the primary tumors. Plain
      radiographs showed ill-defined metastatic lesions. Scintigram using radiolabeled
      metaiodobenzylguanidine, an analogue of noradrenaline that is taken up by
      neurosecretary granules, showed an abnormal accumulation in the corresponding
      metastatic lesion. Histologically, nests of epithelioid cells with clear
      cytoplasm and pyknotic nuclei and abundant collagen fibers were observed within
      destroyed trabeculae. Treatment including external radiation and surgery provided
      pain relief and early local disease control.

PMID- 9526778
TI  - Intraosseous meningioma.
AB  - A 71-year-old woman with a long history of slowly progressive proptosis was found
      to have an intraosseous meningioma of the right sphenoid bone. Radiologically,
      the lesion resembled fibrous dysplasia. The key to the diagnosis is irregularity
      of the inner table of the skull. The histologic appearance is characteristic.
      Intraosseous meningioma is one part of the spectrum of diseases known as primary
      extraneuraxial meningioma. In this paper we discuss the theories of cellular
      origin as well as the radiologic differential diagnosis.

PMID- 9526779
TI  - Granulocytic sarcoma (chloroma) of the sacrum: initial manifestation of leukemia.
AB  - We present an unusual case of a granulocytic sarcoma (chloroma) of the sacrum
      which predated the initial clinical manifestation of acute myelogenous leukemia.
      Although granulocytic sarcomas occur in up to 9.1% of cases of acute myelogenous
      leukemia they usually present concurrently with the leukemic presentation.
      Although granulocytic sarcomas can involve several different organ systems, bone
      is the most common site.

PMID- 9526780
TI  - Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease)
      presenting with skeletal lesions.
AB  - A 2-year-old child presenting with bone pain and bone lesions was found to have
      sinus histiocytosis with massive lymphadenopathy (SHML). SHML presenting with
      skeletal symptoms is unusual. Management has been conservative and the child has
      been symptom free for 30 months, although the bone lesions have not completely
      regressed.

PMID- 9526781
TI  - [Dementia and self-determination].

PMID- 9526782
TI  - [Long-term health policy: a matter of wanting to and acting].

PMID- 9526783
TI  - [Screening for breast cancer in The Netherlands: age discrimination of older
      women?].

PMID- 9526784
TI  - [Memory training for remembering names: initial results in the healthy elderly].
AB  - In this study, a memory training program for remembering names was developed. It
      was assumed that names are remembered better if they have meaning. The effect of
      training is compared with two control conditions a) a placebo training, aimed at
      reducing worries about forgetfulness by giving information about memory and aging
      and b) a retest control group. Participants were healthy persons over 43 years
      old (M = 70 years) having subjective memory complaints and objective memory
      problems. The effect of training is evaluated with tasks for remembering names.
      Because the learned memory strategy can be applied to these tasks, these are
      called target memory tests. Other evaluation measures concerned remembering
      verbal information and intentions. These are called control memory tests, because
      the memory strategy learned cannot be applied directly. In accordance with the
      expectations, performance in the placebo training group (n = 10) did not improve
      more than in the retest control group (n = 11). The names training group (n = 13)
      improved more than both control groups on tests for remembering names. This
      improvement was maintained for at least three months after training. As expected,
      the improvement in performance on the target memory tests did not generalize to
      the control tasks, because of the specificity of the learned strategies.

PMID- 9526785
TI  - [Dementia. Outlook on current developments].
AB  - The results of recent neuropathologic and genetic studies in Alzheimer's disease
      led to a renewed interest in differentiations within the dementia syndrome. New
      disease-entities can be distinguished (Lewy Body Dementia, Frontal Lobe Dementia)
      and other criteria have been put forward for vascular dementia. Hachinski's
      Ischemic Score, for many years the diagnostic criterium for vascular dementia,
      has been cancelled. Instead a CT- or MRI scan must demonstrate the vascular
      pathology in the brain. For clinical practice, the differentiation between
      cortical and subcortical dementia is still important. For reasons of management
      it appears useful to distinguish between early-onset and late-onset Alzheimer's
      disease. The amyloid cascade hypothesis for the pathogenesis of Alzheimer's
      disease is credible for the early-onset as well as the late-onset type, because
      results from epidemiological as well as from neurobiological studies might be fit
      in. Moreover, this hypothesis is promising from the point of view of developing
      specific therapies. Finally, the breakdown of the dementia syndrome in separate
      disease-entities stimulated interest in the psychiatric symptoms in these
      patients and activated the development of rational and symptomatic therapeutics.

PMID- 9526786
TI  - [Risk of hip fractures in the elderly: biomechanical aspects of the falling
      process].
AB  - Age-related fractures are considered to be primarily the consequence of bone loss
      and increased bone fragility. In line with this dominant view on fracture
      etiology, prevention studies have primarily focused on pharmacologic
      interventions to increase bone density of the femoral neck. However, osteoporotic
      fracture occurrence is not entirely accounted for by bone strength but also
      related to the incidence and impact of falls. Recent data have provided evidence
      that an intensive multifactorial intervention strategy can be used to decrease
      the incidence of falls, but it remains to be determined whether fall prevention
      can be used successfully to prevent fall-related injuries or hip fracture. In
      fact, while more than 90% of hip fractures involve falls, hip fracture occurs in
      only about 1% of falls, suggesting that falls that cause hip fracture may differ
      qualitatively from other falls. These differences relate to the biomechanical
      aspects of falls, i.e., the energy that is ultimately transmitted to the proximal
      femur. Fall severity, rather than fall initiation, may therefore have to be the
      primary subject of future research.

PMID- 9526788
TI  - [Social security at the advent of the 21st century].

PMID- 9526787
TI  - [Medical students' image of the elderly and the effect of medical education: a
      literature review].
AB  - In American studies in the sixties and seventies caregivers, including
      physicians, showed a negative attitude towards the elderly. There are indications
      that such a negative attitude affects the quality of care and the communication
      with the elderly. Based on predominantly American literature this article reviews
      research on medical students' knowledge about and attitudes towards older people
      as well as the impact of geriatric training on the image of older patients and
      physician-patient communication. In medical students who did not receive a
      geriatric training, attitudes improved in the eighties and nineties up till a
      slightly positive level but general gerontological knowledge displayed as many
      shortcomings as in former days. A few studies show that instructional modules in
      geriatrics do not have an impact on the attitude towards the elderly. Several
      studies show that contact with aged persons has a positive influence. Rather than
      geriatric residency or work in a nursing home, contact with healthy elderly has
      favourable effects. Attitude improvement based on interactions with older people
      is maintained during medical education. A program in gerontology as well as
      geriatric instructional modules can lead to knowledge improvement. Since
      significantly positive correlations between knowledge and attitude are sometimes
      demonstrated, increasing gerontological knowledge may lead to more positive
      attitudes.

PMID- 9526789
TI  - [Towards a more humane care for the elderly. Ethical reflection].
AB  - Care for the elderly needs not only attention, but also reflection. Every future
      scenario points at a great increase in number and proportion of the elderly. Most
      discussions focus on (scarcity of) resources and their allocation. In other
      words: discussions on means. But first, a reflection on values and goals is
      needed. In this article possible goals for elder care are discussed. Is 'to
      become as old as possible' a goal worth aiming for? The older we get, the longer
      the period of morbidity may be, and all we may get are more illness years. If, on
      the other hand, the goal is to grow old in a healthy way', isn't then health care
      for the elderly in a way 'too late in the day'? Is the improvement of global
      (physical, mental and social) well-being of the elderly a realistic goal in the
      domain of health care? The question arises which motives and values play a part
      in such goals, especially when the goal is to keep elderly 'active and self
      supporting as long as possible'. This article pleads for a moral progress in the
      care for the elderly. What old people need most, is time, attention and interest
      from the people around them.

PMID- 9526790
TI  - [An uneasy balance].
AB  - Impairment of mobility is common in older people. Early detection of this
      impairment can identify persons at risk of a decrease in the ability to perform
      activities of daily living, recurrent falls and deconditioning. Using only
      standard neuromuscular and orthopedic examinations physicians may overlook
      important deficits in mobility. Direct assessment is necessary to identify such
      deficits. Several formal gait assessment instruments are available, such as the
      Tinetti performance-based mobility assessment. In order to illustrate the
      additional value of functional assessment the medical history of two patients is
      described.

PMID- 9526792
TI  - [Burden on caregivers of residents of homes for the aged. An exploratory study].
AB  - In research on caregivers of the frail elderly most attention has until now been
      paid to the burden of caregivers of the demented elderly. However, several
      studies have shown that other groups of carers are also heavily burdened. The
      present study focused on the burden of 73 caregivers of the residents of two
      homes for the elderly. About one fourth of the caregivers felt heavily burdened.
      The mental health of the caregivers, measured with the General Health
      Questionnaire, could not be distinguished from the general population.
      Significant associations were found between the burden and the gender of the
      caregivers, the gender of the elderly person, the time spent on caring, the
      number of caring tasks, and the amount of support from others. Family caregivers
      seemed to have relatively little need for information and advice.

PMID- 9526791
TI  - [Inflammatory mechanisms in the pathogenesis of Alzheimer's disease].
AB  - Senile plaques belong to the pathological hallmarks of the brains of patients
      with Alzheimer's disease. There is an increasing amount of evidence that the
      formation of senile plaques is accompanied by an acute phase reaction, involving
      the production of several inflammation-associated proteins and the activation of
      microglial cells. The products of these inflammatory reactions may contribute to
      the fibrillogenesis of the amyloid beta protein, the major constituent of senile
      plaques. Both fibrils of the amyloid beta protein and products of activated
      microglial cells may be neurotoxic, leading to neuronal degeneration and to
      clinical symptoms of dementia. Recent epidemiological findings have drawn
      attention to the possibility of therapy with anti-inflammatory agents. Although
      the results of these studies suggest a beneficial effect of such therapy, further
      study is warranted to gain more insight into the fundamental aspects of such
      treatment as well as to develop specific drugs that have little side-effects.

PMID- 9526793
TI  - [Abbreviated form of the Informant Questionnaire on cognitive decline in the
      elderly].
AB  - This study evaluated some psychometric qualities of the Dutch short form
      Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE-N). The score
      profile on the short form IQCODE-N was comparable in two outpatient populations.
      Short form and regular IQCODE-N are equivalent, as they were highly correlated (r
      = 0.97). However, using IQCODE-N cut-off scores the short form appeared to be
      more strict in defining 'decline'. A moderately high correlation was found
      between informant ratings and dementia screening tests CST (r = -0.47) and ADS (r
      = -0.46). Informant ratings were not influenced by patient's age or level of
      education. The short form IQCODE-N describes cognitive change in everyday
      activities of elderly patients and can be an efficient rating scale for clinical
      assessment of dementia.

PMID- 9526794
TI  - [Poverty in the elderly. Status, gaps in research and policy].

PMID- 9526795
TI  - [Habermas' and Giddens' modernization theories applied to homes for the aged and
      to somatic nursing homes. The long road toward greater equivalence between
      residents and staff].
AB  - The situation in homes for the elderly and nursing homes is for the residents
      both alarming and tragic. Recent Dutch legislation supports the movement towards
      more self-determination and autonomy for the residents. The staff are dedicated
      to making the living situation as good as possible for the residents.
      Nevertheless many publications describe how the dependence and helplessness of
      the residents stil continue. In this paper this helplessness is placed within the
      broader framework of modern society by application of Habermas' theory of
      communicative action and Giddens' structuration theory. Both theories show that
      the key to improve dependent making structures should be sought principally in
      the behaviour of both staff and residents. Habermas offers a perspective to more
      equivalent communicative action between residents and staff. Giddens draws
      attention to the knowledgeability of residents, with which they should be able to
      interact on an equal basis with professionals. This presupposes much dedication
      of both staff and residents.

PMID- 9526796
TI  - [Cerebrovascular lesions and depression].
AB  - In this article the authors describe two different ways in which the relationship
      between affective disorders and cerebrovascular disease can be studied. First,
      the occurrence of so called 'post stroke depression' offers an opportunity to
      study this relationship. Second, neuroradiological investigations in patients
      with a major depressive disorder can be performed. The authors review the
      literature on both subjects. Until now, unequivocal conclusions concerning
      vascular lesions on CT or MRI and depressive features in the elderly cannot be
      drawn from research data available. Moreover, the so-called Post-stroke
      depression is still not fully understood. Some difficulties encountered in this
      area of research are also addressed. The authors suggest a neurological cause for
      the late onset types of major depressive illness and also suggest that these
      depressions are phenomenologically different from the early onset subtypes of
      depressive illness. The post stroke depression also seems to differ
      phenomenologically from major depression according to DSM-criteria.

PMID- 9526797
TI  - [Disorders of the oral mucosa in the elderly].
AB  - The oral mucosa of the elderly may be affected by a variety of diseases. The
      majority of such diseases are rather harmless and may occur in younger patients
      as well. Furthermore, a number of oral lesions may be the result of neglect of
      the dentition or the dentures. Particularly in the elderly, however, one should
      take into account the possibility of a malignant or premalignant lesion.
      Therefore, careful attention should be paid to any ulcerative lesion of the oral
      mucosa and to white or red changes that are not easily recognizable as a benign
      disease entity. Also pigmented lesions of the oral mucosa should be looked upon
      with suspicion. In elderly patients several oral and perioral complaints may be
      present of which the etiology is unknown. An example of such complaints is the so
      called burning mouth syndrome.

PMID- 9526798
TI  - [Diagnosis of prostate cancer in urination disorders in urological practice:
      current status and future developments].
AB  - This paper presents the current diagnostics of patients with prostate related
      problems (lower urinary tract symptoms) who visit the urology clinic. The
      diagnostic triad for prostate cancer detection is presented, consisting of a
      serum Prostate-Specific Antigen test, a digital rectal examination to palpate the
      prostate, and transrectal ultrasound of the prostate to visualise internal
      structures and guide the urologist in taking biopsies. The results of the tests
      for a biopsied population of 232 patients illustrate the shortcomings of the
      individual tests in predicting the presence of a malignancy. Biopsies are needed
      to prove or rule out prostate cancer in case of a suspicion. Future developments
      in early detection of prostate cancer are directed to improve the clinical use of
      the current diagnostic triad, and to identify new diagnostic tools.

PMID- 9526799
TI  - [Elderly patients with vulvar carcinoma: should we use standard treatment?].
AB  - Invasive squamous cell cancer of the vulva is predominantly a disease of older
      women. Current standard treatment entails a radical local excision with bilateral
      groin node dissection through separate incisions. In individual patients with
      superficially invasive small tumors the groin dissection can be omitted and in
      patients with well lateralized tumors a contralateral groin dissection is not
      always necessary. In the past the 'en bloc' resection of the vulva and groin
      nodes was the standard treatment for every patient. With the introduction of the
      above mentioned modifications, resulting in less morbidity, more older patients
      can now get the standard treatment. A retrospective analysis of all patients with
      vulvar cancer registered in a region in the Netherlands was carried out. The
      objective was to determine the referral pattern and the number of patients who
      received standard treatment. Sixty-seven of the 138 patients were not referred to
      a gynecological oncology center. Of this group the patients with squamous cell
      cancer (n = 36) 80% did not get standard treatment. Compared with the group of
      patients who did get standard treatment, these patients were older (median 81
      years) and had an earlier stage of the disease. A higher than expected recurrence
      rate of 46% and a lower than expected survival rate of 68% was found. During
      follow-up several patients were found to be medically fit enough to undergo
      extensive salvage surgery for this recurrence. From the results of this study it
      can be concluded that deviation from standard treatment in early vulvar cancer
      only on the basis of old age results in decreased survival. Only the performance
      status of the patient combined with clinical and pathological prognostic
      variables should be used to decide what treatment is best for which patient.

PMID- 9526800
TI  - Molecular mechanism of heme biosynthesis.
AB  - Two of the major organs producing heme are bone marrow and the liver. delta
      Aminolevulinate synthase (ALAS) plays the key role to regulate heme biosynthesis
      in hepatocytes as well as in erythroid cells. In the liver, nonspecific (or
      housekeeping) isozyme of ALAS (ALAS-N) is expressed to be regulated by its end
      product, heme, in a negative feedback manner. The way to regulate ALAS-N in the
      liver is suitable to supply a constant level of heme for a family of drug
      metabolizing enzymes, cytochrome P-450 (CYP). In erythroid tissues, not only
      erythroid-specific isozyme of ALAS (ALAS-E) but also ALAS-N are expressed, and
      regulated by distinctive manners. Although heme regulates ALAS-N in a negative
      feedback manner even in erythroid cells, ALAS-E is upregulated by induced heme
      concentration. ALAS-N in undifferentiated erythroid cells, therefore, is
      suggested to produce heme for CYP, whereas heme for accumulating hemoglobin (Hb)
      in cells undergoing differentiation is synthesized via ALAS-E. In this article,
      we describe the molecular mechanisms to regulate heme biosynthesis in non
      erythroid as well as in erythroid tissues, and discuss the pathological
      significance of the mechanisms in patients with inherited disorders, porphyrias.

PMID- 9526801
TI  - Genoepidemiology and pathogenicity of hepatitis G virus in Japan.
AB  - A recently discovered non-A non-B hepatitis virus has been designated hepatitis G
      virus (HGV). Blood contamination has been proposed as its mode of transmission.
      We studied the genoprevalence of HGV in Japanese people at high risk. HGV was
      identified in serum by a reverse-transcription polymerase chain reaction. HGV was
      detected in 16.0% of intravenous drug users (IDUs) (n = 25), 16.2% of those with
      tattoos (n = 37), 10.9% of IDUs with tattoos (n = 55), 5.7% of chronic hepatitis
      (CH)-C patients (n = 87), and in none of the CH-B (n = 50) or CH non-B non-C (n =
      46) patients. Serum alanine aminotransferase (ALT) levels of those infected with
      HGV alone (n = 3) were all within normal range. In the patients with CH-C, serum
      ALT levels of those coinfected with HGV were similar to serum ALT levels of those
      without HGV infection. A phylogenetic tree of isolated HGV clones showed that the
      HGVs of these subjects bore only a distant-resemblance to clones reported from
      Africa and North America, and that variation in the phylogenetic index of HGV
      clones was small. These results suggest that HGV clones from different areas have
      genetic heterogeneity and that HGV causes no or mild hepatitis.

PMID- 9526802
TI  - In-utero transplantation of fetal hematopoietic cells in the mouse: the effect of
      donor and recipient gestational maturity.
AB  - To investigate the possibility of engrafting fetal liver hematopoietic cells by
      in utero intraperitoneal transplantation, we transplanted donor cells obtained
      from mouse fetuses at 13, 15 and 17 days of gestation to mouse fetuses at 15, 16
      and 17 days of gestation. Engraftment was assessed by Sry gene amplification of
      DNA extracted from peripheral blood samples of transplanted mice six weeks after
      birth. In comparison, we performed an in vitro colony-assay of fetal liver cells
      at 13, 15, and 17 days of gestation. The incidence of engraftment was
      significantly higher in cells of 15 days of gestation than in cells of 13 or 17
      days of gestation, whereas the colony forming activity decreased gradually from
      13 to 15 days of gestation. From these results, we suggest that the 15 day liver
      contains hematopoietic progenitors which have the specific characteristics
      required for engraftment by intraperitoneal transplantation.

PMID- 9526803
TI  - Tumor necrosis factor-alpha and transforming growth factor-beta production by
      isolated mononuclear cells from the spinal cords of Lewis rats with experimental
      autoimmune encephalomyelitis.
AB  - We demonstrated time course of the number of mononuclear cells (MNCs) isolated
      from spinal cords (SCs) correlates with the degree of experimental autoimmune
      encephalomyelitis (EAE) of Lewis rats, and analyzed their tumor necrosis factor
      (TNF)-alpha and transforming growth factor (TGF)-beta production by MNCs, using
      enzyme-linked immuno sorbent assay and enzyme-linked immuno spot (ELISPOT) assay.
      The number of MNCs varied from 5 to 620 x 10(4) per SC of normal Lewis rat and
      Lewis rat with EAE. MNCs increased and reached a peak on day 2 post clinical
      onset (Day 2), and subsequently declined through the clinical course. The
      increase of infiltrating MNCs in SCs paralleled the severity of the disease
      development. TGF-beta 1 in plasma of rats with EAE significantly increased on Day
      1 and reached the peak on Day 3. TNF-alpha levels in culture supernatants of MNCs
      from SCs increased on Day 1, and it decreased from Day 2, and declined on Day 4
      when animals began to recover. TGF-beta 1 was not detected in culture supernatant
      during the whole clinical course. The number of TNF-alpha and TGF-beta 1
      producing cells that were detected by ELISPOT assay increased on Day 0, and
      decreased rapidly after the onset of neurological symptoms. Thus, increase of TNF
      alpha appeared in the early phase of the disease and then promptly decreased. In
      contrast, TGF-beta 1 was activated during the later recovering phase of the
      disease. We consider that TNF-alpha may play an important role in the
      pathogenesis of EAE and TGF-beta may inhibit the development of EAE.

PMID- 9526804
TI  - Transrectal ultrasonic planimetry of the prostate in relation to age and lower
      urinary tract symptoms among elderly men in Japan.
AB  - The aim of the present study is to correlate transrectal ultrasonic planimetric
      parameters of the prostate in relation to age and urinary symptoms as evaluated
      by the American Urological Association (AUA) symptom index score for benign
      prostatic hyperplasia (BPH). In 647 examinees on a mass screening program for
      prostatic diseases using transrectal sonography (TRS) in Japan, prostatic volume,
      transition zone volume, transition zone index (transition zone volume/prostatic
      volume) and presumed circle area ratio (PCAR) were determined using transrectal
      ultrasonic planimetry and compared with age and AUA symptom score. Increase in
      age, prostatic volume, transition zone volume and PCAR were significantly
      correlated with AUA symptom score. However, multiple regression analysis
      demonstrated that age and PCAR were the only significant independent determinant
      of symptom score. In particular, PCAR was the only significant determinants of
      symptom score in men with an intermediately enlarged prostate (20-30 ml in
      volume). The most significant difference in AUA symptom score was found between
      subgroups divided by PCAR with a cutoff point of 0.8. Among the planimetric
      parameters obtained by TRS, PCAR was the most powerful for evaluating BPH in
      terms of the severity of lower urinary tract symptoms.

PMID- 9526805
TI  - Diffuse lipomatosis: imaging features.
AB  - A case of diffuse lipomatosis is reported. A 54-year-old man presented with a
      large mass in the left gluteal region. Plain radiographs showed hyperostosis of
      the phalanx of the left third toe. The diagnosis was aided by magnetic resonance
      imaging and computed tomography which clearly demonstrated a diffuse overgrowth
      of fatty tissue in the left buttock and the extremity involving the subcutaneous
      and gluteal muscular tissue.

PMID- 9526806
TI  - Consensus statement: Role of therapy with "statins" in patients with
      hypertriglyceridemia.

PMID- 9526807
TI  - Hypertriglyceridemia as a cardiovascular risk factor.
AB  - To determine the relation between plasma triglyceride levels and the risk of
      incident cardiovascular disease, the semiquantitative techniques of meta-analysis
      were applied to 17 population-based prospective studies of triglyceride and
      cardiovascular disease. Sixteen of these studies represented 2,445 events among
      46,413 Caucasian men followed for an average period of 8.4 years, and 5 studies
      represented 439 events among 10,864 Caucasian women followed for an average
      period of 11.4 years. Univariate relative risk (RR) estimates for incident
      cardiovascular disease associated with a 1-mmol/L increase in triglyceride was
      1.07-1.98 in men, with a summary RR of 1.32 (95% confidence interval [CI]: 1.26
      1.39), indicating a 32% increase in disease risk associated with increased
      triglyceride. In the studies involving women, individual RR estimates for
      triglyceride were 1.69-2.05, with a summary RR of 1.76 (95% CI: 1.50-2.07),
      indicating a 76% increase in disease risk associated with increased triglyceride.
      After adjustment for high-density lipoprotein cholesterol and other risk factors,
      these risks were decreased to 14% in men and 37% in women but remained
      statistically significant. Three recent prospective epidemiologic studies have
      also shown that plasma triglyceride and low-density lipoprotein particle size
      predict subsequent coronary artery disease in Caucasian populations. Taken
      together, these studies demonstrate the importance of triglyceride levels as a
      risk factor for cardiovascular disease.

PMID- 9526808
TI  - Atherogenicity of triglyceride-rich lipoproteins.
AB  - There is increasing evidence that alterations in metabolism of triglyceride-rich
      lipoproteins are of importance in the pathogenesis of atherosclerosis and its
      clinical consequences. Particles with the characteristics of triglyceride-rich
      lipoprotein remnants have been related to the extent and severity of
      atherosclerosis in humans and in animal models. These particles can be identified
      using ultracentrifugal procedures as small, very low-density lipoprotein (VLDL)
      and intermediate-density lipoprotein (IDL) with Svedberg flotation rates (Sf) of
      12-60. Postprandial triglyceride levels also have been related to risk of
      coronary artery disease, consistent with a pathologic role for remnant
      lipoproteins. In studies in which measurements of lipoprotein subfractions have
      been carried out, levels of IDL have been more predictive than low-density
      lipoprotein (LDL) of atherosclerosis progression as assessed by coronary artery
      angiography or carotid artery ultrasonography. These findings suggest that a
      considerable portion of the coronary disease risk attributed to LDL may be
      accounted for by the IDL particles included in standard LDL measurements. Other
      metabolic changes associated with increased levels of plasma triglyceride may
      also adversely affect cardiovascular disease risk. These include reductions in
      HDL-cholesterol and apoprotein A1, increased levels of small dense LDL particles,
      redistribution of apoC-III from HDL to apoB-containing lipoproteins, diminished
      insulin sensitivity, and procoagulant changes, including increased levels of the
      fibrinolysis inhibitor, plasminogen-activator inhibitor-1 (PAI-1). A predominance
      of small dense LDL (subclass pattern B) is a discrete marker for this cluster of
      interrelated abnormalities and is found in 40-50% of patients with coronary
      artery disease. Therapeutic interventions with favorable effects on components of
      this dysmetabolic profile appear to be of value in decreasing atherosclerosis
      risk in a substantial proportion of the population.

PMID- 9526809
TI  - Hypertriglyceridemia, atherogenic dyslipidemia, and the metabolic syndrome.
AB  - The importance of high serum cholesterol, especially a high level of low-density
      lipoprotein (LDL) cholesterol, as a risk factor for coronary artery disease is
      well established. Likewise, efficacy for decreasing risk for coronary artery
      disease by LDL-lowering therapy has recently been documented through clinical
      trials. However, many high-risk patients manifest elevated serum triglyceride
      levels, and the role of hypertriglyceridemia in causation of coronary artery
      disease remains to be elucidated. Nonetheless, there is growing evidence that
      hypertriglyceridemia is a marker for increased risk for coronary artery disease;
      in fact, it can serve as a marker for several atherogenic factors. These factors
      include increased concentrations of atherogenic triglyceride-rich lipoproteins;
      the atherogenic lipoprotein phenotype, or lipid triad; and the metabolic
      syndrome. The lipid triad consists of elevated serum triglycerides, small LDL
      particles, and low high-density lipoprotein (HDL) cholesterol. The metabolic
      syndrome includes the coexistence of the lipid triad, elevated blood pressure,
      insulin resistance (plus glucose intolerance), and a prothrombotic state. Many
      previous studies indicate that hypertriglyceridemia is strongly associated with
      all of these atherogenic factors. The clinical approach to treatment of patients
      with hypertriglyceridemia thus requires a broad-based strategy that includes
      reduction of atherogenic triglyceride-rich lipoproteins, reversal of the lipid
      triad, and favorable modification of the metabolic syndrome. The development of
      therapeutic regimens to effect these changes poses a challenge for future
      research on the problem of hypertriglyceridemia.

PMID- 9526811
TI  - Effects of statins on triglyceride metabolism.
AB  - Hepatic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or
      "statins," have been extremely efficacious in decreasing low-density lipoprotein
      (LDL) cholesterol levels in patients with hypercholesterolemia and in treating
      patients with dysbetalipoproteinemia, a relatively rare form of hyperlipidemia.
      Clinical trials have indicated that statins can significantly lower very-low
      density lipoprotein (VLDL) triglyceride levels, although the central mechanism of
      action of statins-i.e., increasing the number of LDL receptors-would appear to
      suggest that they would have no significant effect on VLDL levels. Through a
      review of published data from animal and human studies, this article addresses
      the important clinical question of how drugs that inhibit the rate-limiting
      enzyme for cholesterol can affect triglyceride metabolism.

PMID- 9526810
TI  - Rationale for use of non-high-density lipoprotein cholesterol rather than low
      density lipoprotein cholesterol as a tool for lipoprotein cholesterol screening
      and assessment of risk and therapy.
AB  - The plasma level of low-density lipoprotein (LDL) cholesterol is the "gold
      standard" for estimating the lipoprotein-related risk for complications of
      atherosclerotic vascular disease. LDL cholesterol concentrations are commonly
      estimated by the Friedewald formula that requires only the measurement (after
      overnight fasting) of plasma cholesterol and triglycerides along with high
      density lipoprotein (HDL) cholesterol. This value, however, is not in fact a true
      estimate of LDL cholesterol but rather of LDL cholesterol along with variable,
      usually smaller, amounts of intermediate-density lipoprotein (IDL) cholesterol
      and lipoprotein(a). Estimation of LDL cholesterol levels by the Friedewald
      formula becomes progressively less accurate as plasma triglyceride concentrations
      increase, and the formula is generally considered inapplicable when triglyceride
      levels exceed 400 mg/dL. We believe that a very simple measurement-non-HDL
      cholesterol (serum cholesterol minus HDL cholesterol)-has considerable potential
      as a screening tool for identifying dyslipoproteinemias, for risk assessment, and
      for assessing the results of hypolipidemic therapy. Unlike the estimation of LDL
      cholesterol levels by the Friedewald formula, the estimation of non-HDL
      cholesterol concentrations requires no assumptions about the relation of very-low
      density (VLDL) cholesterol levels to plasma triglyceride concentrations. This
      method includes all of the cholesterol present in lipoprotein particles now
      considered to be potentially atherogenic [VLDL, IDL, LDL, and lipoprotein(a)].
      This article provides examples of the utility of non-HDL cholesterol
      concentrations in clinical medicine.

PMID- 9526812
TI  - Effect of statins on metabolism of apo-B-containing lipoproteins in
      hypertriglyceridemic men.
AB  - Our investigations indicate that most patients with moderate hypertriglyceridemia
      have marked defects in the metabolism of low-density lipoprotein (LDL)
      apolipoprotein B. Moreover, these patients have 2 major defects in the metabolism
      of triglyceride-rich lipoproteins, i.e., an accumulation of remnant lipoproteins
      (due in part to delayed hepatic clearance) and increased fractional conversion of
      very-low-density lipoprotein (VLDL) to LDL. Defective triglyceride-rich
      lipoprotein metabolism has been associated with insulin resistance. Statin
      therapy in hypertriglyceridemic patients improves the lipoprotein profile by
      decreasing both LDL cholesterol and remnant lipoproteins. However, statin therapy
      does not normalize LDL apolipoprotein B metabolism, and high-density lipoprotein
      (HDL) cholesterol levels remain low. Therefore, consideration may be given to
      combining a statin with a drug that alters triglyceride metabolism (e.g., fibrate
      or nicotinic acid) in high-risk patients with hypertriglyceridemia.

PMID- 9526813
TI  - Role of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors ("statins") in
      familial combined hyperlipidemia.
AB  - Familial combined hyperlipidemia (FCHL) is a heterogeneous genetic disorder
      characterized by multiple lipoprotein phenotypes. The genetic defect is unknown,
      although linkage to the region of the apolipoprotein (apo) A-I-apoC-III-apo A-IV
      gene cluster on chromosome 11 has been suggested. The metabolic abnormality in
      many affected individuals is overproduction of apoB-containing lipoproteins
      causing elevated levels of plasma cholesterol, triglycerides, or both. Low levels
      of high-density lipoprotein (HDL) cholesterol and an abundance of dense low
      density lipoprotein (LDL) particles are other features contributing to the high
      association of this disorder with premature coronary artery disease. Many
      affected individuals need drug therapy to lower their lipid levels. The hepatic 3
      hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or "statins,"
      offer a potent therapeutic option in patients with FCHL. These drugs
      significantly decrease levels of total cholesterol, LDL cholesterol, and apoB,
      although their effects on HDL cholesterol and triglycerides are limited. The
      mechanisms by which statins exert their beneficial effects in patients with FCHL
      remain controversial. We studied 7 patients with FCHL and 5 genetically
      uncharacterized patients with mixed lipemia during treatment with pravastatin 20
      mg/day. Metabolic parameters of very-low-density lipoprotein (VLDL)-apoB and LDL
      apoB were studied using endogenous labeling with stable isotopes. In all patients
      pravastatin caused an increase in fractional catabolic rates of LDL-apoB without
      a significant effect on the production rates of apoB-containing lipoproteins. We
      cannot exclude the possibility that higher doses of statins may decrease VLDL and
      LDL production.

PMID- 9526814
TI  - Treatment of diabetic dyslipidemia.
AB  - Patients with diabetes mellitus have an increased risk for coronary artery
      disease due to hyperglycemia, hypertension, dyslipidemia, and other risk factors.
      The diabetic dyslipidemia in these patients is characterized by moderately high
      levels of (1) serum cholesterol and triglycerides; (2) small, dense low-density
      lipoprotein (LDL) particles; and (3) low high-density lipoprotein (HDL) cho
      lesterol concentrations. Recent clinical trials have demonstrated the benefits of
      cholesterol-lowering therapy in both diabetic and nondiabetic patients, thus
      supporting aggressive treatment of diabetic dyslipidemia for coronary artery
      disease prevention. A 3-step approach is recommended for the treatment of
      diabetic dyslipidemia. First, modification of diet and lifestyle, including
      decreased intakes of cholesterol, cholesterol-raising fats, and total energy, and
      increased physical activity should be advised. Second, good glycemic control
      should be achieved with diet and hypoglycemic drugs, if needed. Third, lipid
      lowering drugs should be used, if necessary. Non-HDL cholesterol levels, which
      include both very-low-density lipoprotein (VLDL) and LDL cholesterol, should be
      the target of cholesterol-lowering therapy. The use of 3-hydroxy-3-methylglutaryl
      coenzyme A reductase inhibitors (the "statins") has become the first-line drug
      therapy for diabetic dyslipidemia. Bile acid sequestrants are effective
      cholesterol-lowering agents in normotriglyceridemic patients with non-insulin
      dependent diabetes mellitus (NIDDM). Patients with severe hypertriglyceridemia
      may require fibric acids or n-3 polyunsaturated fatty acids. Nicotinic acid
      worsens hyperglycemia; therefore, it should be avoided in most cases. The
      efficacy and safety of estrogen-replacement therapy in postmenopausal women with
      diabetes needs to be determined. The combination of two lipid-lowering agents may
      be appropriate for some NIDDM patients but should be used judiciously.

PMID- 9526815
TI  - Use of niacin, statins, and resins in patients with combined hyperlipidemia.
AB  - Patients in the original Familial Atherosclerosis Treatment Study (FATS) cohort
      were subgrouped into those with triglyceride levels < or = 120 mg/dL (n = 26) and
      those with triglyceride levels > or = 190 mg/dL (n = 40). Their therapeutic
      responses to niacin plus colestipol, lovastatin plus colestipol, colestipol
      alone, or placebo were determined. Therapeutic response was also determined in
      the same 2 triglyceride subgroups (n = 12 and n = 27, respectively) of patients
      selected for low levels of high-density lipoprotein (HDL) cholesterol and
      coronary artery disease. These triglyceride criteria were chosen to identify
      patient subgroups with high likelihood of "pattern A" (normal-size low-density
      lipoprotein [LDL] particles and triglyceride < or = 120 mg/dL) or "pattern B"
      (small dense LDL and triglyceride > or = 190 mg/dL). Our findings in these small
      patient subgroups are consistent with the emerging understanding that coronary
      artery disease patients presenting with high triglyceride levels have lower HDL
      C, smaller less buoyant LDL-C, and greater very low-density lipoprotein (VLDL)
      cholesterol and VLDL apolipoprotein B, and are more responsive to therapy as
      assessed by an increase in HDL-C and reduction in triglycerides, VLDL-C, and VLDL
      apolipoprotein B. In the FATS high-triglyceride subgroup with these
      characteristics, a tendency toward greater therapeutic improvement in coronary
      stenosis severity was observed among those treated with either of the 2 forms of
      intensive cholesterol-lowering therapy. This improvement is associated with
      therapeutic reduction of LDL-C and elevation of HDL-C, but also appears to be
      associated with drug-induced improvement in LDL buoyancy.

PMID- 9526816
TI  - Long-term efficacy and safety of fenofibrate and a statin in the treatment of
      combined hyperlipidemia.
AB  - To assess the long-term efficacy and use of fenofibrate together with a 3-hydroxy
      3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor ("statin") in the
      treatment of elevated levels of triglycerides and low-density lipoprotein (LDL)
      cholesterol, we conducted a study that compared a before- and after-case series.
      The study involved 80 patients with a diagnosis of combined hyperlipidemia and
      existing coronary artery disease (81% of patients) or outpatients with > or = 3
      risk factors for coronary artery disease who had been receiving treatment at a
      tertiary care center. Fasting biochemical measures were obtained at baseline
      during monotherapy with a statin consisting of pravastatin 20 mg once daily or
      simvastatin 10 mg once daily (39 patients) or fenofibrate 300 mg once daily (41
      patients), and during a 2-year period of combination therapy. This combination
      therapy comprised fenofibrate 300 mg once daily or micronized fenofibrate 200 mg
      once daily taken together with pravastatin 20 mg once daily (63 patients) or
      simvastatin 10 mg once daily (17 patients). The main outcome measures were: (1)
      absolute and percent change in total cholesterol, triglycerides, LDL cholesterol,
      and high-density lipoprotein (HDL) cholesterol; (2) percentage of patients with
      alanine aminotransferase > or = 2x the upper limits of normal on any occasion;
      (3) percentage of patients with creatinine kinase > or = 3 times the upper limits
      of normal on any occasion; (4) absolute changes in alanine aminotransferase and
      creatinine phosphokinase; and (5) months on combination therapy. Patients
      receiving combination therapy had a mean total cholesterol (+/- standard error of
      the mean [SEM]) that was significantly decreased by 26+/-1%, triglycerides by
      41+/-3%, and LDL cholesterol by 28+/-2%, and mean HDL cholesterol that was
      significantly increased by 22+/-6%. These changes correspond to mean absolute
      changes of total cholesterol: -75+/-5 mg/dL; triglycerides: -94+/-13 mg/dL; LDL
      cholesterol: -52+/-5 mg/dL; and HDL cholesterol: 5+/-1 mg/dL. During combination
      treatment, alanine aminotransferase increased by 2+/-2 U/liter (not significant)
      and creatinine phosphokinase decreased by 4+/-13 U/liter (not significant).
      During treatment, 8 patients (10%) had transitory isolated elevations in alanine
      aminotransferase levels > or = 2 times the upper limits of normal and 2 patients
      (2.5%) had an isolated and transitory elevation of creatinine kinase (> or = 3x
      but < 6x upper limits of normal) without associated muscle symptoms. Patient
      years on combination therapy equaled 220.6 (average 2.06 years per patient). The
      results demonstrated that combination treatment with fenofibrate and low-dose
      simvastatin or pravastatin is generally safe and effective for the treatment of
      combined hyperlipidemia in patients with normal hepatic and renal function.

PMID- 9526817
TI  - Comparison of statins in hypertriglyceridemia.
AB  - In 1996, the first 2 studies using 3-hydroxy-3-methylglutaryl coenzyme A (HMG
      CoA) reductase inhibitor ("statin") therapy in hypertriglyceridemic subjects were
      published. In subjects with isolated triglyceride elevations who were treated
      with atorvastatin 5, 20, and 80 mg/day, large and dose-related reductions were
      noted. In subjects with combined hyperlipidemia treated with 10 mg simvastatin,
      triglyceride reduction similar to that reported for the 5 mg atorvastatin dose
      was seen. In response to these findings, we conducted comparative assessments to
      determine whether all statins are effective in lowering triglyceride levels and
      whether their effect on triglycerides is related to factors such as drug, dose,
      and baseline triglyceride levels. To standardize these assessments, we devised a
      ratio that related changes in triglyceride levels to the known predictable
      response of low-density lipoprotein (LDL) cholesterol to statins. This
      triglyceride/LDL cholesterol ratio was obtained by dividing the percent change
      from baseline in the triglyceride level by the percent change from baseline in
      the LDL cholesterol level. The triglyceride/LDL cholesterol ratio was initially
      applied to several published studies, and found to be approximately 1.0 and 0.5
      in hypertriglyceridemic and nonhypertriglyceridemic populations, respectively. We
      then assessed the effect of various statins on triglycerides using a pooled
      laboratory database of 2,689 subjects who had participated in 7 separate studies
      with similar designs. All of the studies had a placebo run-in followed by a
      randomized, double-blind, active treatment phase of at least 4 weeks with a
      statin. Entry into these studies required a triglyceride level of <400 mg/dL. In
      subjects with baseline triglyceride >250 mg/dL, significant and dose-dependent
      reductions in triglyceride of 22-45% were seen with all statins. When baseline
      triglyceride was <150 mg/dL, no significant or dose-dependent effect on
      triglyceride was seen. The triglyceride/LDL cholesterol ratio was evaluated using
      a linear model that included baseline triglyceride level, drug, and dose. Only
      the baseline triglyceride level was significantly (p <0.001) related to this
      ratio. Moreover, the triglyceride/LDL cholesterol ratio was fairly constant
      across all statins and doses for patients with baseline triglyceride levels of
      <150 mg/dL, 150-250 mg/dL, and >250 mg/dL, at 0.0+/-0.3, 0.5+/-0.2, and 1.2+/
      0.3, respectively. We conclude that all statins are effective in decreasing
      triglyceride levels, but only in hypertriglyceridemic patients. Due to the
      relatively constant triglyceride/LDL cholesterol ratio, our analysis indicates
      that the more effective the statin is in decreasing LDL cholesterol, the more
      effective it will also be in decreasing triglyceride levels in patients with
      hypertriglyceridemia.

PMID- 9526818
TI  - Serum triglycerides and clinical benefit in lipid-lowering trials.
AB  - Trial evidence shows that effective lowering of serum total cholesterol and
      particularly of low-density lipoprotein (LDL) cholesterol is important for the
      prevention of total mortality, coronary artery disease mortality, and major
      coronary events. The role of serum triglyceride reduction in achieving clinical
      benefit is unclear and poorly documented. On the other hand, no specific trials
      have studied the importance of triglyceride lowering among patients with marked
      hypertriglyceridemia. One of the problems in assessing patients with high serum
      triglyceride levels may be the heterogeneous background of the molecular
      mechanisms that result in hypertriglyceridemia.

PMID- 9526819
TI  - Vaginal and uterine anomalies in the pediatric and adolescent patient.
AB  - Congenital malformations of the vagina, cervix, and uterus, although rare, may
      have profound implications for the young gynecological patient. These anomalies
      are often detected in the adolescent period. For proper management, the physician
      requires a thorough understanding of normal embryology and sexual
      differentiation. Although clinical experience helps the gynecologist appreciate
      the disturbed anatomic configurations, each and every individual who presents
      with a defect must be thoroughly evaluated because genital tract aberrations do
      not necessarily follow any defined and consistent pattern. Other anomalies often
      coexist, particularly related to the renal tract, so a thorough assessment is
      warranted. Genital malformations can be particularly disturbing to the patient
      and her family because they not only have reproductive implications but also
      significant psychological and sexual overtones that need to be addressed and
      dealt with in a sensitive and reassuring manner. This report is meant to provide
      an overview of the various abnormalities encountered and guide the clinician by
      providing an approach to management. A more indepth discussion is best found in
      the classic textbooks (Rock JA: Surgery for anomalies of the mullerian ducts. In:
      Te Linde's Operative Gynecology (8th ed). Edited by J Rock, J. Thompson.
      Philadelphia, Lippincott-Raven, 1997; Edmonds DK: Sexual development anomalies
      and their reconstruction: upper and lower tracts. In: Pediatric and Adolescent
      Gynecology. Edited by J Sanfilippo, D Muram, P Lee, J Dewhurst. Philadelphia,
      W.B. Saunders, 1994; Jones HW Jr: Reconstruction of congenital uterovaginal
      anomalies. In: Female Reproductive Surgery. Edited by J Rock, A Murphy, HW Jones
      Jr. Baltimore, Williams & Wilkins, 1992).

PMID- 9526820
TI  - Menorrhagia in adolescents requiring hospitalization.
AB  - STUDY OBJECTIVE: This study was undertaken to assess the causes and treatments of
      menorrhagia in adolescents hospitalized for this menstrual disorder. DESIGN: A
      retrospective chart review was performed of all adolescents < or =20 years of age
      with menorrhagia admitted at the University of Michigan from 1979 to 1995.
      Information regarding medical history, hematologic parameters, treatment, and
      diagnosis was extracted from each chart. Pregnant and premenarchal patients were
      excluded. RESULTS: Thirty-seven adolescents with 46 admissions for menorrhagia
      were identified. The average age of menarche was 12.9 years and the average age
      at admission was 15.9 years. Nineteen adolescents had significant medical
      diseases. For the 46 admissions, causes of menorrhagia were anovulation (21),
      hematologic disease (15), chemotherapy-related (5), and infections (5).
      Transfusions of blood products were performed in 28 of the admissions. Treatments
      included oral contraceptive pills or progestins (30), intravenous conjugated
      estrogens (8), antibiotics (4), immune gammaglobulin (3), DDAVP (3), and
      prednisone (1). Twelve surgical procedures were performed, including eight
      dilatation and curettages (D&Cs), three laparoscopies, and one hysterectomy.
      CONCLUSIONS: Sixty-one percent of admissions for adolescent menorrhagia were in
      adolescents with significant medical problems. The patients with menorrhagia who
      required admission had severe anemia and were transfused in 63% of cases. The
      predominant causes for these admissions included anovulation in 46%, hematologic
      disease in 33%, chemotherapy in 11%, and infection in 11%. Hormonal regulation or
      suppression of menses should be considered in adolescents with significant
      medical disease.

PMID- 9526821
TI  - Young women's attitudes toward injectable and implantable contraceptives.
AB  - STUDY OBJECTIVE: To assess the potential acceptability of implantable and
      injectable contraceptive characteristics by young women of diverse ethnic and
      educational backgrounds. DESIGN: A cross-sectional self-administered survey.
      SETTINGS: The waiting room of three clinical sites: an elite women's college
      health service, a coeducational state university health service, and an inner
      city hospital-based adolescent clinic. PARTICIPANTS: 328 young women awaiting
      medical care in one of three clinical sites, aged 13 to 21 years (85% 18-21
      years); ethnic distribution differed significantly by site. The majority (83%)
      were sexually active, and of those who were sexually experienced, 25% had been
      pregnant. OUTCOME MEASURES: A 47-item questionnaire examining attitudes toward
      characteristics of injectable and implantable contraceptive methods, menstrual,
      sexual, and gynecologic history. RESULTS: Sixty-two percent of the sample agreed
      that they would get an injectable method. There was little variation in agreement
      to get an injectable method by sexual or pregnancy history. Fewer subjects (24%)
      agreed that they would like to get subdermal implants and agreement to get an
      implantable method of contraception did not vary by sexual history; however, ever
      pregnant young women (33%) were significantly more likely to agree to implants
      than never-pregnant subjects (21%; chi2, 4.109; p = 0.04). Seventy-four percent
      of subjects said they would stop using a contraceptive that caused irregular
      menses, whereas 65% would stop using a method that caused amenorrhea.
      CONCLUSIONS: An injectable contraceptive method has universal appeal across
      ethnic, educational, and age categories, whereas implants are less appealing.
      Irregular bleeding and amenorrhea are poorly perceived side effects of long
      acting contraceptives.

PMID- 9526822
TI  - Uterus didelphys with unilateral imperforate hemivagina and ipsilateral renal
      agenesis.
AB  - Eight patients with a double uterus, unilateral vaginal obstruction, and
      ipsilateral renal agenesis are described. The most common clinical presentation
      was that of the onset of pelvic pain and dysmenorrhea, in association with the
      finding of a pelvic mass. In seven patients, a window was created between two
      vaginae by transvaginal route. In one patient, the blind vagina with hematocolpos
      and attending uterus were extirpated by an abdominal approach. The postoperative
      courses were uncomplicated in all patients. A greater awareness of this syndrome
      should lead to accurate diagnosis. Excision of the obstructing vaginal septum
      offers a complete relief of symptoms while preserving reproductive capacity.

PMID- 9526824
TI  - Norplant failure: an adolescent case study and review of the literature.
AB  - STUDY OBJECTIVE: To alert clinicians to risk factors associated with
      levonorgestrel implant (Norplant; Wyeth-Ayerst Laboratories, Philadelphia, PA)
      failures in the adolescent population and discuss alternatives. DATA SOURCES:
      Medline search of articles pertaining to the use of levonorgestrel implants in
      the adolescent population. STUDY SELECTION: All articles pertaining to the use of
      levonorgestrel implants in adolescents. CONCLUSIONS: Levonorgestrel subdermal
      implants, Norplant, have been successfully used worldwide as contraceptives.
      Clinical trials suggest that pregnancy rates while using levonorgestrel implants
      are positively correlated with increased body weight. In addition, pregnancy
      rates may be higher in women below age 25 years. Finally, patients who report
      regular menstrual cycles on levonorgestrel implants may be at greater risk for
      method failure. Consequently, despite its apparent success, levonorgestrel
      implants have some significant but little-known limitations that should be
      considered in initial adolescent patient selection, education, and postinsertion
      medical supervision.

PMID- 9526823
TI  - Recurrent benign mullerian papilloma of the cervix.
AB  - A 4-year-old girl with a recurrent benign cervical mullerian papilloma is
      presented. Benign mullerian papillomas are rare cervical and vaginal lesions of
      childhood, with only two recurrences previously reported. This lesion was
      originally biopsied and later rebiopsied and completely fulgarated with
      electrocautery. One year later, the lesion recurred and was biopsied but not
      completely excised because of concern that complete excision of this benign,
      asymptomatic lesion would cause significant damage to her cervix. A review of the
      literature on this subject is presented.

PMID- 9526825
TI  - Diagnosis of 5alpha-reductase deficiency in a teenage Turkish girl.
AB  - Deficiency of 5alpha-reductase type 2 activity causes deficient masculinization
      of 46,XY individuals caused by a lack of dihydrotestosterone. At puberty,
      virilization is often observed. A precise diagnosis with correct gender
      assignment at an early age is very important. Recently, the molecular basis of
      the enzyme defect was discovered; however, only a few cases of 5alpha-reductase
      deficiency with a complete molecular genetic analysis have been published. We
      report on a Turkish patient clinically classified with steroid 5alpha-reductase
      deficiency (SRD) type 3b (karyotype 46,XY) who was raised as a girl and presented
      to us at the age of 14 years because the male phenotype had become predominant at
      puberty. Endocrinological investigations revealed an elevated serum
      testosterone/dihydrotestosterone ratio (17.3, normal: <16). PCR-SSCP analyses
      detected a deletion of methionine on exon 3 of the 5alpha-reductase type 2 gene.

PMID- 9526826
TI  - Management quandary. Diagnosis of lichen sclerosus.

PMID- 9526827
TI  - Lichen sclerosus.

PMID- 9526828
TI  - Stress, diet and alcohol-induced oxidative gastrointestinal mucosal injury in
      rats and protection by bismuth subsalicylate.
AB  - Oxygen free radicals are implicated in the pathogenesis of stress and
      food/alcohol-induced gastrointestinal injury. We have investigated the effects of
      restraint stress, spicy food diet, high-fat diet and 40% ethanol on the enhanced
      production of reactive oxygen species, including superoxide anion and hydroxyl
      radicals, and on DNA fragmentation, lipid peroxidation and membrane
      microviscosity (indices of oxidative tissue damage) in gastric and intestinal
      mucosa of Sprague-Dawley rats. Furthermore, the protective ability of bismuth
      subsalicylate (BSS; 15 mg kg(-1) was determined against the gastrointestinal
      mucosal injury induced by these stressors. Animals on the high-fat diet consumed
      31% more food as compared to other animals. Animals on the spicy food diet
      consumed ca. 23% more water as compared to control animals, and the high-fat diet
      animals consumed 17% less water. Restraint stress provided greater injury to both
      gastric and intestinal mucosa as compared to other stressors. Restraint stress,
      spicy food diet, high-fat diet and ethanol increased superoxide anion production
      by 10.0-, 4.3-, 5.7- and 4.8-fold, respectively, in the gastric mucosa, and by
      10.4-, 5.3-, 7.0- and 5.5-fold in the intestinal mucosa. Exposure to restraint
      stress, spicy food diet, high-fat diet and 40% ethanol also increased hydroxyl
      radical production by ca. 14.3-, 4.5-, 3.5- and 4.8-fold, respectively, in the
      gastric mucosa, and by 17.0-, 4.8-, 3.5- and 4.7-fold in the intestinal mucosa.
      Bismuth subsalicylate administration to the animals provided significant
      protection against superoxide anion and hydroxyl radical production. Restraint
      stress, spicy food diet, high-fat diet and ethanol increased lipid peroxidation
      by 3.6-, 2.4-, 2.6- and 2.0-fold, respectively, in the gastric mucosa, and by 4.1
      , 3.5-, 3.6- and 2.7-fold in intestinal mucosa. Administration of BSS decreased
      restraint stress, spicy food diet, high-fat diet and ethanol-induced gastric
      mucosal lipid peroxidation by ca. 26%, 36%, 45% and 18%, and intestinal mucosa
      lipid peroxidation by 20%, 21%, 46% and 42%, respectively. Approximately 4.0-,
      2.0-, 2.4- and 2.0-fold increases in DNA fragmentation were observed in the
      gastric mucosa of rats exposed to restraint stress, spicy food diet, high-fat
      diet and 40% ethanol, respectively, and similar increases in the intestinal
      mucosa. These same four stressors increased membrane microviscosity by 11.6-, 6.1
      , 7.3- and 5.4-fold, respectively, in the gastric mucosa, and by 16.2-, 7.9-, 9.5
      and 7.8-fold in the intestinal mucosa. Bismuth subsalicylate exerted significant
      protection against DNA damage and changes in membrane microviscosity induced by
      the four stressors. Excellent correlations existed between the production of
      reactive oxygen species and the tissue damaging effects in both gastric and
      intestinal mucosa. In summary, the results demonstrate that physical and chemical
      stressors can induce gastrointestinal oxidative stress and mucosal injury through
      enhanced production of reactive oxygen species, and that BSS can significantly
      attenuate gastrointestinal injury by scavenging these reactive oxygen species.

PMID- 9526829
TI  - Effect of the menstrual cycle in ethanol pharmacokinetics.
AB  - Differences in ethanol pharmacokinetics within the menstrual cycle have
      previously been reported and attributed to variations in body composition,
      hormonal influences and gastric emptying. To establish the role of the menstrual
      cycle in ethanol pharmacokinetics associated with changes in body composition,
      ethanol blood concentrations were measured in nine healthy women during the
      midfollicular (P1, days 8-10) and midluteal (P2, days 22-24) phases of the
      menstrual cycle after a postprandial oral ethanol dose (0.3 g kg(-1)). Total body
      water was assessed by dual-energy x-ray densitometry (DEXA) on both occasions.
      Median total body water did not vary during either phase of the menstrual cycle
      (P1 = 54.54%, P2 = 54.66%; P = 0.9296). Median area under the ethanol
      concentration-time curve (AUC) was lower during P1 (215.33 mg.h dl(-1)) than
      during P2 (231.33 mg.h dl(-1))(P = 0.8253). No significant differences were found
      on ethanol pharmacokinetics in either phase of the menstrual cycle.

PMID- 9526830
TI  - Hemizygous Tg.AC transgenic mouse as a potential alternative to the two-year
      mouse carcinogenicity bioassay: evaluation of husbandry and housing factors.
AB  - The dermal Tg.AC transgenic mouse model has been proposed as a potential
      alternative to the conventional (e.g. oral, dermal, parenteral, inhalation, etc.)
      2-year rodent bioassay for detecting chemical carcinogenicity. The present study
      was designed to address a number of technical aspects of this model as well as to
      augment the database being developed with the Tg.AC system at the NIEHS.
      Hemizygous Tg.AC mice were implanted s.c. with microchips for identification and
      housed individually in polycarbonate (i.e. 'plastic') or suspended stainless
      steel wire-bottom (i.e. 'metal') cages. Treatment consisted of dermal application
      of the test or control material in treatment volumes of 200 microl of acetone.
      Groups of 10 males and 10 females were treated as follows: G1--shaved, no
      treatment; G2--acetone control seven times a week; G3--100 microl of benzene
      three times a week; G4--150 microl of benzene three times a week; G5--1.25 microg
      of phorbol ester (PMA) twice a week. The G1-G5 mice were housed in plastic caging
      with Alpha-dri bedding. Three additional groups were housed in stainless-steel
      wire-bottom caging: G6--shaved, no treatment; G7--acetone control seven times a
      week; G8--1.25 microg of PMA twice a week. The PMA-treated mice (G5 and G8)
      served as the positive controls. Mice were treated for 20 weeks followed by a 6
      week recovery period prior to necropsy. The incidence of dermal papillomas in the
      shaved area was recorded weekly. There were no spontaneous papillomas in the
      target area of any of the untreated (G1) or vehicle control (G2) animals in the
      polycarbonate cages. One papilloma was observed in the untreated mice (G6) and
      one in the vehicle control group (G7) in the steel cages. This suggests that the
      type of caging, the shaving process, microchip implantation and daily acetone
      treatment for 20 weeks are all consistent with a very low background incidence of
      papillomas in this model. Papillomas were observed in the positive control groups
      as early as 4 weeks of treatment and increased both in number per mouse and
      number of mice affected up to a maximum average of 3.5 papillomas per mouse and
      55% (11/20) mice with papillomas in G5 and 2.7 and 80% (16/20) in G8. A plateau
      was reached at about week 13 and the numbers of papillomas remained stable
      through the rest of the treatment and recovery phases. The low dose of benzene
      (100 microl) showed no significant effect, whereas the higher dose (150 microl)
      produced a moderate number of papillomas beginning at about week 11. The results
      of this study are comparable with earlier studies at the NIEHS and indicate
      reproducibility between laboratories and that the Tg.AC transgenic mouse model is
      suitable for use in an industrial pre-clinical safety evaluation context.

PMID- 9526831
TI  - Relative neurotoxicological properties of five unsaturated aliphatic nitriles in
      rats.
AB  - Motor and sensory conduction velocities (MCV and SCV) and amplitudes of the
      sensory and motor action potentials (ASAP and AMAP) of the tail nerve were
      studied in male Sprague-Dawley rats during chronic oral treatment with five
      unsaturated aliphatic nitriles. Rats were given doses of 12.5, 25 and 50 mg kg(
      1) of acrylonitrile, 50, 70 and 90 mg kg(-1) of methacrylonitrile, 25, 50 and 100
      mg kg(-1) of trans-3-pentenenitrile and 50, 100 and 200 mg kg(-1) of either 3
      methyl-2-butenenitrile or 4-pentenenitrile once a day, 5 days per week for 12
      weeks. Moreover, due the the early results obtained after oral treatment,
      neurophysiological examinations were also carried out in rats exposed by
      inhalation to 25, 50 and 100 ppm of acrylonitrile for 6 h a day, 5 days per week
      for 24 weeks. Rats given acrylonitrile orally developed behavioural sensitization
      characterized by salivation, locomotor hyperactivity and moderately intense
      stereotypies. Moreover, rats in the high dose group developed weakness in
      hindlimbs associated with decreases in SCV and ASAP. Rats exposed to
      acrylonitrile vapours exhibited time- and concentration-dependent decreases in
      MCV, SCV and ASAP, which were partially reversible after 8 weeks of recovery.
      None of the other four nitriles caused any abnormal behaviour or any changes in
      the electrophysiological parameters in spite of an obvious general toxicity.
      Based upon these results, it can be concluded that the nervous system of the rat
      appears to be a target following either oral or inhalation exposures of
      acrylonitrile.

PMID- 9526832
TI  - Combined pulmonary toxicity of diethyldithiocarbamate and lead (II) oxide in
      rats.
AB  - The pulmonary toxicity of sodium diethyldithiocarbamate and lead(II) oxide alone
      or in combination was studied in rats after a single intratracheal instillation.
      The lead content in the lungs and the whole blood was determined and it has been
      found that the clearance of lead from the lung was delayed by dithiocarbamate
      complex formation, which probably had a role in increased IgA levels in the
      bronchoalveolar fluid and the induction of local immune response. The combined
      exposure gave rise to calcium deposits in the lungs both extra- and
      intracellularly after 1 month of exposure. Both separate and combined exposure
      invoked permanent injury in membranes or dystrophic changes in the cytoplasm of
      pneumocytes, which may initiate and generate a series of events leading to
      fibrosing alveolitis.

PMID- 9526833
TI  - Peripheral markers (Clara cell protein and alpha-glutathione S-transferase) and
      lipidoperoxidation (malondialdehyde) assessment in Sprague-Dawley rats instilled
      with haematite and benzo[a]pyrene.
AB  - The literature suggests that the concomitant exposure to polycyclic aromatic
      hydrocarbons (PAH) and ferric oxide particles could enhance lung cancer incidence
      in environmental and occupational settings. High levels of tracheobronchial
      tumours were obtained in hamsters exposed to benzo[a]pyrene (B[a]P) adsorbed onto
      ferric oxide carrier particles. Therefore, we have assessed the toxic effects of
      exposure to haematite (Fe2O3) and B[a]P in male Sprague-Dawley rats. Animals were
      instilled with the chemicals alone (3 mg of Fe2O3 or B[a]P) or in combination (3
      mg Fe2O3 + 3 mg B[a]P). Bronchoalveolar lavages (BAL) and biological samples
      (serum and urine) were collected 48 h after the intoxication. Clara cell protein
      (CC16) and alpha-glutathione S-transferase (alpha-GST), as peripheral markers of
      both tracheobronchial epithelial cell integrity and renal dysfunction, were
      determined in BAL fluid, serum and urine. Malondialdehyde (MDA), a marker of
      lipid peroxidation, was measured in BAL fluid and serum. We observed a
      significant increase of CC16 concentrations in BAL fluid after Fe2O3 + B[a]P
      instillation (p < 0.05) in serum after Fe2O3 and Fe2O3 + B[a]P exposure (p <
      0.01) and in urine after B[a]P administration (p < 0.01). Instillation of Fe2O3 +
      B[a]P produced an increased amount of alpha-GST in BAL fluid (p < 0.01), whereas
      B[a]P alone caused a significant elevation of alpha-GST in serum and urine (p <
      0.01). Moreover, Fe2O3 or Fe2O3 + B[a]P instillation induced a significant
      increase in MDA levels in BAL fluid (p < 0.01 and p < 0.05). In conclusion, Fe2O3
      may have a low pulmonary toxicity. However, B[a]P manifested a rapid and high
      toxicity in the respiratory tract and kidneys. When B[a]P was adsorbed on
      haematite particles, both its retention in the respiratory tract and pulmonary
      toxicity increased.

PMID- 9526834
TI  - Oligofructose modulates lipid metabolism alterations induced by a fat-rich diet
      in rats.
AB  - The aim of this study was to test the hypothesis that non-digestible fructans,
      namely oligofructose (OFS), are able to decrease post-prandial lipaemia in rats
      fed a high-fat diet composed of 10% lard, 4% corn oil and 0.15% cholesterol. Male
      Wistar rats were divided into three groups: group 1 was fed a standard low-fat
      diet (AO4), group 2 received the high-fat diet (HF) and group 3 received 10%
      (w/w) OFS in the HF diet (HF-OFS) for 3 weeks. The OFS supplementation reduced
      post-prandial triglyceridaemia by more than 50%, compared to both AO4 and HF
      groups. It also protected rats against the increase in free cholesterol serum
      level induced by the HF diet. The OFS did not prevent the HF-induced hepatic
      accumulation of triglycerides, phospholipids and cholesterol; however,
      histochemical analysis showed smaller lipid droplets in the liver of HF-OFS rats
      as compared to HF rats. Our results suggest that, when given in HF diet, OFS
      decreases serum triglycerides through an extra-hepatic event, namely by enhancing
      triglyceride-rich lipoprotein catabolism.

PMID- 9526835
TI  - No involvement of system N, system y+ and the oligopeptide-H+ transport system in
      the uptake of methylmercury in rat erythrocytes.
AB  - Previous studies have investigated a number of possible transport systems for the
      uptake of methylmercury (MeHg) in erythrocytes. In the present study, three
      additional systems were studied. The uptake of MeHg by isolated erythrocytes from
      rats was studied at 5 degrees C and 20 degrees C. Glutamine was used to test
      system N and system y+, and glycylglycine was used to test the oligopeptide-H+
      transport system. The Hill equation was used in kinetic analysis. The results
      show that both glutamine and glycylglycine stimulated the uptake of MeHg, but the
      stimulation by glycylglycine is stronger than by glutamine, and the stimulation
      at 5 degrees C is stronger than at 20 degrees C (mean values are 167.98% and
      83.68% in the glycylglycine group at 5 degrees C and 20 degrees C versus 26.28%
      and 19.23% in the glutamine group at 5 degrees C and 20 degrees C). The kinetic
      analysis shows that: the Michaelis-Menten constant Km increased as temperature
      increased in both groups and was larger in experimental groups than in control
      groups; the Hill constants increased as temperature increased in both groups and
      were smaller in experimental groups than in control groups; and as temperature
      increased, maximum velocity Vmax increased in control groups and decreased in
      experimental groups, and was larger in experimental groups than in control
      groups, with the exception of the glycylglycine group at 20 degrees C. The
      results demonstrated that system N, system y+ and oligopeptide-H+ transport
      systems were not involved in the in vitro uptake of MeHg into erythrocytes. The
      stimulation by glutamine and glycylglycine might be related to some signalling
      pathways, through which nitric oxide and oligopeptide serve as messengers and
      cause functional alterations in the uptake of MeHg.

PMID- 9526836
TI  - Behavioural and neurotoxicological changes caused by cadmium treatment of rats
      during development.
AB  - Behavioural and electrophysiological changes caused by inorganic cadmium were
      investigated in the offspring of female Wistar rats. Dams were given 3.5, 7.0 or
      14.0 mg kg(-1) cadmium (cadmium chloride dissolved in distilled water) in three
      different treatment regimes: days 5-15 of pregnancy; days 5-15 of pregnancy + 4
      weeks of lactation; days 5-15 of pregnancy + 4 weeks of lactation followed by the
      same oral treatment of male rats of the F1 generation for 8 weeks. The
      behavioural (open-field exploration) and electrophysiological
      (electrocorticogram, cortical evoked potentials, conduction velocity and
      refractory periods of a peripheral nerve) parameters of F1 male rats exposed by
      various treatments were investigated at the age of 12 weeks. It was found that
      cadmium dose and treatment time dependently altered the spontaneous and evoked
      electrophysiological functions (e.g. increased the frequency of the
      electrocorticogram, lengthened the latency and duration of evoked potentials,
      etc.). Interestingly, only the combination of treatment during prenatal
      development and the 4-week suckling period resulted in a significant dose
      dependent decrease of horizontal and vertical exploratory activity and a
      significantly lower exploration frequency of the open-field centre. The results
      showed that low-level pre- and postnatal inorganic cadmium exposure affects the
      bioelectrical and higher order functions of the nervous system. In the case of
      human populations, a similar prolonged exposure might be just as harmful.

PMID- 9526837
TI  - Effects of neonatal quinalphos exposure and subsequent withdrawal on free radical
      generation and antioxidative defenses in developing rat brain.
AB  - Ten-day-old rat pups were given quinalphos (QP, 0.5 mg kg(-1)) orally up to
      postnatal days (PND) 21 or 45. A group of rats exposed to QP was withdrawn from
      the treatment at PND 21 and was killed at PND 45 for the withdrawal study.
      Acetylcholinesterase decreased in the brain and blood after QP exposure but
      recovered after withdrawal. Superoxide radical generation in brain was increased
      by 43%, 59% and 39% following exposure up to PND 21 and 45 and in the withdrawal
      group, respectively. Quinalphos did not alter hydrogen peroxide formation but
      increased hydroxyl radical (19%) production at PND 45. Quinalphos elevated the
      activities of superoxide dismutase by 30%, (although the increase from 0.24 to
      0.31 was physiologically not significant) and catalase by 50% at PND 21, which up
      on withdrawal of the exposure at PND 22 recovered partially or completely at PND
      45. However, the continuous exposure up to PND 45 decreased superoxide dismutase
      (63%) and catalase (31%) activities. Selenium-independent glutathione peroxidase
      (GPx) was increased at PND 21 (31%) and PND 45 (152%) after QP exposure and there
      was complete recovery after withdrawal. Selenium-dependent GPx, which was
      elevated slightly at PND 21, was also normalized after withdrawal. Prolonged
      exposure to QP did not alter the ascorbic acid content and produced a marked
      decrease in cerruloplasmin (46%) levels. Brain glutathione levels increased
      marginally in QP-exposed rats and became normal in the withdrawal group.
      Quinalphos exposure up to PND 45 enhanced brain lipid peroxidation (28%) and
      decreased vitamin E levels (15%). It appears that neonatal QP exposure produces
      cerebral oxidative stress, which may result in deleterious effects on central
      nervous system function immediately and in later life.

PMID- 9526838
TI  - Fluorinated anesthetics differ in toxic effects on peritoneum and subjacent
      tissues.
AB  - Intraperitoneal injection of fluorinated anesthetics produced anesthesia in rats.
      This was followed by toxic effects on peritoneal organs and surfaces, except for
      sevoflurane, which did not produce any lesions.

PMID- 9526839
TI  - Interferon beta normalizes suppressor cell function in dysimmune neuropathies.
AB  - We found a defective suppressor cell function in vitro both in idiopathic chronic
      inflammatory demyelinating polyneuropathy and in paraproteinemic neuropathy with
      antibodies to sulfated glucuronyl paragloboside. In the presence of interferon
      beta, suppressor cell function was normalized. Our results suggest that a
      decreased suppressor cell function plays a pathogenetic role in dysimmune
      neuropathies. Interferon beta might represent an adjunctive therapy in CIDP both
      acting on a defective blood-nerve barrier and normalizing an otherwise defective
      suppressor cell function.

PMID- 9526840
TI  - Soluble Fas (Apo-1) levels in cerebrospinal fluid of multiple sclerosis patients.
AB  - CSF and serum levels of soluble Fas were studied in MS patients, in patients with
      various neurological diseases and in healthy controls. We did not detect
      differences in serum sFas levels between MS patients and controls. In CSF,
      despite sFas levels being similar in all patients studied, a statistically
      significant correlation between sFas CSF/sFas serum ratio and BBB damage
      (expressed as albumin CSF/albumin serum ratio) was detected in non-MS
      neurological disease, but not in MS patients. The normalized ratio (sFas CSF/sFas
      serum)/(Alb CSF/Alb serum) was significantly increased in MS patients compared to
      patients with non-inflammatory neurological disease suggesting an intrathecal
      synthesis of soluble Fas in MS. The percentage of apoptotic mononuclear cells was
      higher in CSF as compared to peripheral blood; moreover a lower proportion of
      apoptotic cells was found in CSF of MS patients. The findings lend support to the
      involvement of sFas in MS pathogenesis and suggest that a lower apoptosis in CSF
      may be a feature of the disease.

PMID- 9526841
TI  - Expression of the CB1 cannabinoid receptor in macrophage-like cells from brain
      tissue: immunochemical characterization by fusion protein antibodies.
AB  - Antibodies designed to recognize a 74 amino acid sequence of the N- or C-terminal
      domain of the rat CB1 cannabinoid receptor detected a 58 kDa protein in
      immunoblots of brain and various cells known to express the CB1 cannabinoid
      receptor. A human B-lymphoblastoid cell line and macrophage-like cells from
      neonatal rat brain were also positive for CB1 receptor-like immunoreactivity.
      Immunocytochemical analysis performed with isolated Fab fragments showed surface
      staining in NG108-15 cells and brain macrophage like cells which also express MHC
      class II antigens. The data suggest a plausible role for CB1 receptors in the
      immune function of brain.

PMID- 9526842
TI  - Expression of IL-12 in CNS and lymphoid organs of mice with experimental allergic
      encephalitis.
AB  - EAE is a Th1 cell-mediated inflammatory autoimmune demyelinating disease of the
      central nervous system. IL-12 is a 70 kd heterodimeric cytokine, capable of
      regulating a wide range of immune functions. In view of its crucial role in the
      development of Th1 immune responses, we studied the expression of IL-12 p40 in
      the CNS and lymphoid organs of mice with EAE. RT-PCR analysis showed an increase
      in the expression of IL-12 p40 in brain and spinal cord during the acute
      paralytic phase of EAE and that decreased upon clinical recovery. The expression
      of p40 mRNA was also increased in spleen, lymph node and liver along with an
      elevated levels of circulating serum IL-12 during the height of disease. In vivo
      administration of rIL-12 increased the proliferative response and IFN-gamma
      production of MBP sensitized T cells and that was decreased following treatment
      with anti-IL-12 antibody. The expression of IL-12 in the target and lymphoid
      organs of animals with EAE, the induction of a Th1 type immune response following
      immunization with neuronal antigens and the inhibition of clinical disease upon
      treatment with anti-IL-12 antibody, suggest the crucial role of IL-12 in the
      pathogenesis of EAE.

PMID- 9526843
TI  - Opposite regulation of prostaglandin E2 synthesis by transforming growth factor
      beta1 and interleukin 10 in activated microglial cultures.
AB  - We have recently shown that prostaglandin E2 (PGE2) synthesis in activated
      microglia is tightly regulated by several substances (NO, neurotransmitters, pro
      inflammatory cytokines), that might originate from intrinsic brain cells or from
      hematogenous cells infiltrating the brain in the course of inflammatory diseases.
      In view of the important immunoregulatory and neuroprotective functions recently
      attributed to PGE2, in the present study we extended our analysis of factors
      regulating PGE2 synthesis in rat microglial cultures to two anti-inflammatory and
      immunosuppressive cytokines, transforming growth factor beta1 (TGF-beta1) and
      interleukin 10 (IL-10), which share with PGE2 the ability to strongly deactivate
      peripheral macrophages and microglial cells. Moreover, we looked at the effect of
      the two cytokines on nitric oxide (NO) synthesis, another important microglial
      effector, whose synthesis is linked to that of PGE2 by complex feed-back
      mechanisms. We found that while both cytokines inhibited LPS-induced NO release,
      they had distinct and opposite regulatory activities on PGE2 production. In fact,
      while TGF-beta1 enhanced LPS-induced PGE2 synthesis, IL-10 showed an inhibitory
      effect. The two cytokines acted mainly by regulating the LPS-induced expression
      of the rate limiting enzymes of the two metabolic pathways, cyclooxygenase-2 (COX
      2) and inducible NO synthase (iNOS). Moreover, TGF-beta1 counteracted the effect
      of the pro-inflammatory cytokine interferon-gamma, which in the same cultures has
      been shown to downregulate PGE2 and to upregulate NO synthesis. Although the
      present in vitro observations cannot be directly extrapolated to the in vivo
      situation, they may provide a novel clue for understanding the specific role of
      TGF-beta1 and IL-10 in several neurological diseases such as multiple sclerosis,
      in which their cerebral level was found to be elevated.

PMID- 9526844
TI  - Restraint stress-induced thymic involution and cell apoptosis are dependent on
      endogenous glucocorticoids.
AB  - The aim of this study was to investigate the specific role of endogenous
      glucocorticoids (GC) following restraint stress on thymic involution and
      apoptosis. Restraint stress has been reported to alter physiological and
      behavioral responses in experimental animals. Exposure of mice to restraint
      stress led to involution of the thymus, to a decrease of the CD4+ 8+ thymocyte
      subset, and to fragmentation of thymic DNA. The role of endogenous GC in
      restraint stress-induced changes in the thymus was studied by three experimental
      approaches: surgical adrenalectomy, chemical adrenalectomy, and blocking of GC
      receptors by a specific type II receptor antagonist. In surgically-Adx mice,
      which lack endogenous GC, the effects of restraint on the thymus were wholly
      abrogated. Pretreatment of restrained mice with metyrapone (an 11beta hydroxylase
      inhibitor that specifically inhibits GC biosynthesis) had the same consequence,
      and blockage of GC receptors with the specific GC type II receptor antagonist RU
      38486 attenuated the effects of the stressor. These findings indicate that GC are
      involved in the restraint-induced effects on the thymus.

PMID- 9526845
TI  - The roles of Fas, Fas ligand and Bcl-2 in T cell apoptosis in the central nervous
      system in experimental autoimmune encephalomyelitis.
AB  - The selective apoptotic elimination of autoreactive T cells in the central
      nervous system (CNS) contributes to the resolution of inflammation and the
      spontaneous clinical recovery from experimental autoimmune encephalomyelitis
      (EAE). To assess the molecular mechanisms involved in this process, we used three
      colour flow cytometry to examine the expression of apoptosis-regulating proteins
      by inflammatory cells isolated from the spinal cords of Lewis rats immunized with
      myelin basic protein (MBP) and complete Freund's adjuvant. Throughout the course
      of the disease, which peaked 12-14 days after inoculation and was followed by
      clinical recovery, we analyzed the DNA content of the spinal cord inflammatory
      cells to assess apoptosis and, simultaneously, we measured the expression of five
      proteins (Fas, Fas ligand (Fas-L), Bcl-2, Bcl-x and Bax) which modulate the
      apoptotic process. Cells expressing the death effector molecules Fas and Fas-L
      were particularly prone to undergo apoptosis, and were over-represented in the
      apoptotic population. Of the cells expressing the cell death inhibitor Bcl-2, a
      low proportion were undergoing apoptosis compared to the proportion of the total
      inflammatory cell population undergoing apoptosis, indicating that expression of
      Bcl-2 protects against T cell apoptosis in this disease. There was no evidence,
      however, that the apoptotic regulators Bcl-x and Bax influenced the
      susceptibility to apoptosis. We also found that Vbeta8.2+ T cells, which
      constitute the predominant encephalitogenic MBP-reactive T cell population in the
      Lewis rat, have a high frequency of Fas and Fas-L expression compared to other
      inflammatory cells. This would account for the previously demonstrated
      susceptibility of Vbeta8.2+ T cells to apoptosis in the CNS in EAE. These
      findings support the hypothesis that autoreactive T cells are eliminated from the
      CNS during spontaneous recovery from EAE by activation-induced apoptosis
      involving the Fas pathway.

PMID- 9526846
TI  - Long-term gender-specific effects of manipulation during pregnancy on immune and
      endocrine responsiveness in rat offspring.
AB  - Exposure to synthetic glucocorticoids (GCs) or other stimuli around birth may
      affect neuroendocrine and immune responsiveness in the offspring. Experiments
      were conducted to investigate whether maternal manipulation with saline or with
      GCs alters the corticosterone (CORT) response to a mild stressor in the
      offspring, and whether maternal manipulation results in long-term altered in vivo
      humoral and cellular immune responsiveness in the offspring. Pregnant rats were
      given dexamethasone (DEX, 1.2 mg/kg body weight, i.p.) or saline (SAL) at day 17
      and 19 of gestation. A third group of pregnant rats was left undisturbed (UNTR
      group). After maternal DEX treatment, no altered CORT response was seen to a
      novel environment at 20 days of age, as compared to both the SAL-treated group
      and the UNTR-group. However, saline administration to pregnant rats caused an
      increased CORT response in female offspring, but not male offspring, as compared
      to the UNTR-group (P < or = 0.01). Furthermore, no effects of maternal DEX
      exposure were seen on IgG2a production after immunization with a conjugated
      pneumococcal polysaccharide (PPS-14-CRM197) at 6 weeks of age. However, maternal
      SAL treatment enhanced anti-PPS-14 IgG2a antibody levels in female offspring, but
      not in male offspring, as compared to the UNTR-group (P < or = 0.05). Cellular
      immune responses were measured by an oxazolone-induced contact hypersensitivity
      response (CHS-response), at 8 weeks of age. Maternal SAL treatment increased the
      CHS response in adult male rats, but not in female rats, as compared to both the
      UNTR-group and the DEX-group (P < or = 0.005). These data suggest that
      manipulations during late pregnancy not only affect endocrine responsiveness, but
      also influence immune responsiveness in the rat offspring. Furthermore, these
      effects may be long-term and gender-specific.

PMID- 9526847
TI  - A role of the thymus and thymosin-alpha1 in brain NGF levels and NGF receptor
      expression.
AB  - Using neonatal rats we investigated the role of the thymus and thymosin-alpha1 (T
      alpha1) in brain NGF levels, NGF receptor (p75NGFr) expression, as well as the
      activity of choline acetyl-transferase, a cholinergic enzyme regulated by NGF. It
      is shown that early postnatal thymectomy causes a decrease in NGF in the
      hippocampus and cortex and p75NGFr distribution in the basal forebrain
      cholinergic neurons (FBCN). Intracerebral T-alpha1 injection in thymectomized
      animals induces a recovery, albeit not complete, of both NGF and p75NGFr. These
      findings indicate that thymectomy affects both the brain NGF producing and
      responding cells and that T-alpha1 may be one of the thymic hormones involved in
      the regulation of cerebral NGF synthesis.

PMID- 9526848
TI  - Bacillus Calmette-Guerin sequestered in the brain parenchyma escapes immune
      recognition.
AB  - We have previously shown that heat-killed bacillus Calmette-Guerin (BCG) injected
      into the brain parenchyma becomes sequestered behind the blood-brain barrier for
      months, apparently unrecognised by the immune system (Matyszak and Perry, 1995,
      1996a,b). In this paper we have studied T-cell and antibody responses to purified
      protein derivative (PPD) at different times after intracranial injection of BCG
      or after the same dose of BCG was injected intradermally. We detected no antibody
      to PPD in the sera of animals which received intracranial injection, although
      there was a clear antibody response in the sera of animals injected
      intradermally, as shown using immunoblot analysis. The skin contact sensitivity
      to PPD was robust in animals which had received a previous intradermal injection
      of BCG. 72 h after a PPD injection, the injected site showed many MHC class II +
      macrophages and T-cells. However, the response in skin following PPD challenge,
      in animals injected intracranially (i.c.), was comparable with that of naive
      animals which had received no previous BCG challenge. The skin lesions in animals
      injected i.c. and in naive animals, were characterised by a small number of MHC
      class II + cells and rare T-cells. T-cell responses were also studied in an in
      vitro proliferation assay. The proliferative response was measured for cells
      isolated from the cervical lymph nodes and the spleen. Cells purified from the
      spleen and the cervical lymph nodes of animals injected with BCG i.c. showed no
      specific proliferative response to PPD. The response was comparable to that found
      in naive, uninjected animals. However, spleen and cervical lymph node cells from
      animals injected intradermally with BCG showed a significant proliferative
      response to PPD. These results show that a dose of bacteria injected into the
      brain parenchyma fails to prime the immune system even though the same dose
      injected subcutaneously will do so. This response to bacteria in the CNS differs
      from that previously reported for soluble proteins.

PMID- 9526849
TI  - The effect of melatonin chronic treatment upon macrophage and lymphocyte
      metabolism and function in Walker-256 tumour-bearing rats.
AB  - Melatonin is the main hormone involved in the neuroendocrine-immune axis. It also
      presents antitumour activity. To evaluate the role of melatonin on the
      progression of Walker-256 tumour in rats we determined the effect of the hormone
      on some biochemical and functional aspects of macrophage and lymphocytes from
      cachectic rats. An important finding observed in immune cells from tumour-bearing
      (TB) rats is the impairment on glutamine and glucose metabolism in such cells.
      These changes are very similar to those observed in pinealectomized rats (PNX).
      The increased production of lactate and the flux of glucose through the Krebs
      cycle and the reduction in glutamine consumption seems to be involved in the
      immunosuppression presented in the TB and PNX animals. Melatonin treatment
      restored the changes observed in the metabolism of glucose and glutamine and
      stimulated the proliferation of lymphocytes from tumour-bearing rats. The results
      indicate that the effect of melatonin upon tumour growth involves the stimulation
      of the immune system by the hormone.

PMID- 9526850
TI  - Lymphocyte subsets and CD45RA positive T-cells in normal canine cerebrospinal
      fluid.
AB  - In order to evaluate changes in lymphocyte subpopulations of cerebrospinal fluid
      (CSF) cells in neurological diseases, normal control data have to be established.
      In this study we evaluated CSF samples from 65 dogs of both sexes and various
      breeds with an age range between 5 months and 6 years, and 20 one-year-old
      healthy inbred Beagles. For comparison, blood samples from 10 healthy dogs were
      examined. 14 different antibodies against leukocyte surface markers were used.
      The subpopulations were evaluated using flow cytometry (FACS) and
      immunocytochemistry. It could be shown that lymphocyte populations in CSF differ
      from peripheral blood in a few subsets. A relatively high degree of individual
      variation was found, not only in dogs of different breeds and ages, but also in
      the inbred Beagle population. These large individual variations suggest that
      repeated paired CSF-blood samples during the course of neurological disease
      should be examined within the same individual to obtain meaningful results. CD3+
      and CD4+ T-cells were significantly lower in normal CSF. Of great interest is the
      fact, that T-cells, characterized by double staining CD3/CD45RA are present in
      variable numbers in normal CSF. In other species they are known to be naive or
      resting T-cells. CD4/CD45RA positive cells seem to be an important subpopulation
      of these CD45RA positive T-cells. Furthermore, by far more CD11b positive
      lymphocytes were observed in the CSF than in the peripheral blood and these are
      not large granular lymphocytes. The present study shows that systematic FACS
      analysis of CSF is feasible in larger animals such as dogs.

PMID- 9526851
TI  - T-cell response to myelin basic protein and lipid-bound myelin basic protein in
      patients with multiple sclerosis and healthy donors.
AB  - An autoimmune T-cell response to myelin proteins is thought to be involved in the
      pathogenesis of multiple sclerosis (MS) and myelin basic protein (MBP) is the
      most widely studied potential target antigen. We investigated the T-cell response
      to MBP in MS patients and controls using two different molecular forms of the
      protein: the classical hydrophilic MBP (lipid-free MBP, LF-MBP) and a lipid
      bound, native-like preparation of MBP isolated in a molecular form retaining the
      binding to all myelin lipids (lipid-bound-MBP, LB-MBP). Short term T-cell lines
      (TCL) were generated using either LF- or LB-MBP and tested for their reactivity
      to the in vitro stimulating antigen. No differences were detected between MS
      patients and healthy donors in the percentage of T-cell cultures responsive to
      the LF-MBP. In contrast, the number of LB-MBP reactive cultures was higher in MS
      patients than in controls. This difference was almost entirely due to the
      presence of high numbers of LB-MBP-specific TCL in MS patients which did not
      cross-react with LF-MBP and were not present in healthy subjects. LB-MBP may
      represent a novel antigen worth to be investigated in MS.

PMID- 9526853
TI  - Isolation of porcine circovirus-like viruses from pigs with a wasting disease in
      the USA and Europe.
AB  - Samples of lung, liver, kidney, pancreas, spleen, and lymph node from pigs with
      postweaning multisystemic wasting syndrome from California (USA) and samples of
      mesenteric lymph nodes from similarly diseased pigs from Brittany (France) were
      examined by light microscopy, in situ hybridization (ISH), and/or virus
      isolation. Whole genomic probes for porcine circovirus (PCV) and chicken anemia
      virus (CAV) were used for ISH. Tissue homogenate supernatants were inoculated
      onto PK/15 cells for virus isolation, and the presence of viral antigen and viral
      particles was verified by indirect immunofluorescence, ISH, and electron
      microscopy. Histologic examination of lung from pigs from California revealed
      interstitial pneumonia, alveolar epithelial hyperplasia, and basophilic nuclear
      and cytoplasmic inclusions in mononuclear cell infiltrates and various pulmonary
      epithelial cells. Granulomatous lymphadenitis with syncytial cells typified the
      lesions seen in the pigs from France. PCV-like nucleic acid was detected by ISH
      in lung, pancreas, lymph node, kidney, and liver in pigs from California.
      Positive signal was also obtained in lymph node sections from pigs from France.
      Probes for CAV were consistently negative. PK/15 cell cultures inoculated with
      lung preparations from diseased California pigs and mesenteric lymph node
      preparations from pigs from France had positive fluorescence by indirect staining
      for PCV using pooled polyclonal pig sera and hyperimmune rabbit serum and had
      variable staining with a panel of 7 monoclonal antibodies specific for cell
      culture contaminant PCV. PCV-like nucleic acid was also detected by ISH in cell
      cultures. Cytopathic effect was not observed. Electron microscopic examination of
      inoculated cell cultures revealed 17-nm viral particles morphologically
      consistent with PCV. No other virus particles were observed. Although genomic
      analysis for the definitive identification of these viral isolates remains to be
      done, the evidence provided strongly suggests that these tissue isolates are
      closely related to, although antigenically distinct from, the original PCV cell
      culture contaminant.

PMID- 9526854
TI  - Risk analysis of quarantine station performance: a case study of the importation
      of equine infectious anemia virus-infected horses into California.
AB  - We examined the risk of importing and mistakenly releasing equine infectious
      anemia virus (EIAV)-infected horses into California. A computer simulation model
      was constructed to evaluate current and alternative quarantine station
      procedures; 150,000 iterations were performed to simulate 15 different scenarios
      of 10,000 horses imported into the state over a 14-year period. Simulation
      results showed that under current conditions of low EIAV prevalence in exporting
      countries, increasing the quarantine period would not decrease the number of EIAV
      infected horses mistakenly released from quarantine. In a worst case scenario of
      high EIAV prevalence in exporting countries, the model predicted 10 EIAV-infected
      horses would be imported, of these 1 or none would escape detection and would be
      released mistakenly if quarantine duration were 3 or 14 days, respectively. This
      model may be applied to other quarantine station situations for evaluating the
      importation risk for EIAV and other diseases.

PMID- 9526852
TI  - Induction of choline acetyltransferase mRNA in human mononuclear leukocytes
      stimulated by phytohemagglutinin, a T-cell activator.
AB  - The induction of mRNA for choline acetyltransferase (ChAT), which catalyzes
      acetylcholine (ACh) synthesis was investigated in human mononuclear leukocytes
      (MNL) stimulated by phytohemagglutinin (PHA), a T-cell activator, using the
      reverse transcription-polymerase chain reaction. Stimulation of MNL by PHA
      induced the expression of ChAT mRNA, and potentiated ACh synthesis. ChAT mRNA
      induction required more time than the induction of interleukin-2 mRNA. Expression
      of the gene encoding the vesicular ACh transporter, which mediates ACh transport
      in cholinergic neurons, was not observed in PHA-stimulated MNL, suggesting that
      the mechanisms controlling ACh release from T-lymphocytes differ from those in
      cholinergic neurons. These findings demonstrate that activation of T-lymphocytes
      up-regulates ACh synthesis in the blood, and suggest that ACh plays an important
      role as a neuroimmunomodulator besides its role as a neurotransmitter.

PMID- 9526855
TI  - Immunohistochemical detection of Brucella abortus antigens in tissues from
      aborted bovine fetuses using a commercially available polyclonal antibody.
AB  - A commercially available polyclonal antibody and an avidin-biotin-peroxidase
      immunohistochemical technique were used to detect Brucella abortus antigens in
      formalin-fixed, paraffin-embedded tissues of lung and liver from 20 aborted
      bovine fetuses. Thirteen fetuses were obtained from farms with a previous history
      of brucellosis, and 7 were collected from farms without a history of brucellosis.
      Among the 13 aborted bovine fetuses obtained from farms with a history of
      brucellosis, immunoreactivity to B. abortus was detected in lung (9 fetuses) and
      in liver (1 fetus), whereas Brucella was cultured from abomasal contents in 9
      fetuses (8 were immunohistochemically positive). In addition, 11 dams of these 13
      aborted bovine fetuses had antibodies to Brucella. Brucella abortus was not
      detected by immunohistochemistry in the 7 aborted bovine fetuses collected from
      farms without a history of brucellosis. Bacteriologic culture and serologic tests
      were also negative for Brucella. The results of this study revealed that the
      immunohistochemical technique was sufficiently sensitive for detecting B. abortus
      antigens in formalin-fixed lung tissues from naturally aborted bovine fetuses.
      Although additional studies are necessary to rule out cross-reaction of the
      polyclonal antibody with other microorganisms that cause bovine abortion, this
      immunohistochemical technique could be a complementary tool to serology and
      bacteriology for the diagnosis of brucellosis.

PMID- 9526856
TI  - Changes in levels of viremia in cattle persistently infected with bovine viral
      diarrhea virus.
AB  - Virus isolation and serum neutralizing antibody titers were determined over a
      period of time from samples collected from animals persistently infected with
      bovine viral diarrhea virus (BVDV). To evaluate over time the ability to detect
      BVDV by virus isolation from serum or white blood cell preparations, 4
      persistently infected calves were monitored from birth until 70 days of age. In 3
      of 4 persistently infected calves, virus isolation from serum and white blood
      cells was negative until approximately 42 days of age, when colostral antibody
      had declined. The level of viremia in 7 adult (> 12 months) persistently infected
      animals decreased by 1 10-fold dilution over at least a 2-year period. The level
      of viremia became undetectable by virus isolation from serum in 1 of the 7
      animals examined. This decline was associated with the development of virus
      neutralizing antibody. Although the level of viremia is fairly stable within
      persistently infected animals, the presence of specific neutralizing antibody may
      affect the ability to isolate BVDV. These findings are important when considering
      diagnostic testing to identify persistently infected animals by virus isolation.

PMID- 9526857
TI  - Severe acute bovine viral diarrhea in Ontario, 1993-1995.
AB  - In 1993, noncytopathic bovine viral diarrhea virus (BVDV) strains with enhanced
      virulence caused unprecedented outbreaks of severe acute bovine viral diarrhea
      (BVD) in dairy, beef, and veal herds in Ontario (Canada). Fever, pneumonia,
      diarrhea, and sudden death occurred in all age groups of cattle. Abortions often
      occurred in pregnant animals. Gross lesions in the alimentary tract were similar
      to those associated with mucosal disease, especially in animals >6 months of age.
      Cattle of all age groups had microscopic lesions in the alimentary tract similar
      to those seen with mucosal disease. The epidemic peaked in the summer of 1993,
      with 15% of all bovine accessions from diseased cattle presented to the
      diagnostic laboratory being associated with BVDV. The virus strains involved in
      the outbreak were analyzed using monoclonal and polyclonal antibodies and the
      polymerase chain reaction. The virus isolates from these outbreaks of severe
      disease were determined to be type 2 BVDV. Type 2 BVDV has been present in
      Ontario at least since 1981 without causing widespread outbreaks of severe acute
      BVD, which suggests that type 2 designation in itself does not imply enhanced
      virulence. Cattle properly vaccinated with type 1 BVDV vaccines appear to be
      protected from clinical disease.

PMID- 9526858
TI  - Enteric lesions induced by different pseudorabies (Aujeszky's disease) virus
      strains inoculated into closed intestinal loops of pigs.
AB  - Three different strains of pseudorabies (Aujeszky's disease) virus were
      inoculated into ligated closed loops in the jejunum and ileum of five specific
      pathogen-free pigs. Infected areas were compared with respect to distribution of
      histologic lesions and pseudorabies virus antigen. Two wild-type strains of
      pseudorabies virus produced enteric lesions consisting of necrosis of the
      subepithelial macrophages in the basilar crypt epithelium, necrosis of the
      lymphoid follicles in the Peyer's patches, degeneration of the epithelial cells
      in the crypt and villi, degeneration of the neuronal cells in the myenteric
      plexuses, and formation of intranuclear inclusion bodies on postinoculation days
      2-4. Pseudorabies virus antigen was initially detected in subepithelial
      macrophages of the dome of Peyer's patches on postinoculation day 2 and
      subsequently extended to superficial epithelium and deeper into the lymphoid
      follicles and myenteric plexuses on postinoculation days 3-4. Many pseudorabies
      virus particles were also detected in the center of their necrotic foci. However,
      1 mutant strain (ara-T-resistant) of pseudorabies virus did not produce enteric
      lesions. The results suggest that the primary target of infection by wild-type
      strains of pseudorabies virus might be the macrophages distributed in the
      subepithelial area of the dome Peyer's patches.

PMID- 9526859
TI  - Evaluation of a single dilution ELISA system for detection of seroconversion to
      bovine viral diarrhea virus, bovine respiratory syncytial virus, parainfluenza-3
      virus, and infectious bovine rhinotracheitis virus: comparison with testing by
      virus neutralization and hemagglutination inhibition.
AB  - A single-dilution quantitative enzyme-linked immunosorbent assay (ELISA) system,
      based on commercial ELISA kits, for the simultaneous detection of seroconversion
      to bovine viral diarrhea virus (BVDV), bovine respiratory syncytial virus (BRSV),
      parainfluenza-3 virus (PI3V), and infectious bovine rhinotracheitis virus (IBRV)
      was evaluated by testing acute and convalescent serum pairs from 564 cattle in
      145 outbreaks of respiratory disease. Seroconversion to BVDV, BRSV, PI3V and IBRV
      was detected in 8.0%, 19.0%, 13.7%, and 7.4%, respectively, of serum pairs
      tested. Seroconversion was detected in 60.7% of herds and 34.6% of animals
      tested. Infection with 2 or more viruses was found in 46.6% of these herds and in
      27.2% of these animals. The majority of BVDV infections (62%) were associated
      with other virus infections, suggesting that BVDV may potentiate infection with
      other agents rather than being a primary pathogen of the respiratory tract. The
      results were compared with those obtained by virus neutralization and
      hemagglutination inhibition testing, and the sensitivity, specificity, and
      overall correlation were calculated. Sensitivities of 92%, 95%, 100%, and 100%
      were obtained for BVDV, BRSV, PI3V, and IBRV, respectively. The corresponding
      specificity values were 89%, 92%, 86%, and 91%. The overall correlation for each
      virus was 90%, 93%, 90%, and 93%, respectively. These results demonstrate that
      this ELISA system may be used successfully to detect seroconversion in serum
      pairs, highlight the frequency of multiple viral infections in outbreaks of
      respiratory disease, and provide further evidence of an immunosuppressive role
      for BVDV infections.

PMID- 9526860
TI  - Biovariants of isolates of Pasteurella from domestic and wild ruminants.
AB  - A total of 608 bacterial isolates previously identified as Pasteurella
      haemolytica biotypes A and 3, P. trehalosi, and P. multocida, were separated into
      73 distinct biovariants using 21 phenotypic characteristics. The largest group
      (54%) of wildlife isolates was identified as biogroup 2 and biogroup 2 variants.
      Biogroup 2 and biogroup 2 variants accounted for only 17% of isolates from
      domestic ruminants and were all from sheep. In contrast, 43% of isolates from
      domestic ruminants were identified as biogroup 1 and biogroup 1 variants, whereas
      only 6% of isolates from wildlife were identified in these groups. The majority
      of biogroup 1 isolates from wild ruminants were from 1 group of bighorn sheep in
      Arizona that were geographically separated from other wildlife sampled.
      Similarly, 1 biogroup 2 variant, 2E, was cultured only from free-ranging Dall
      sheep in Alaska. Twelve percent of domestic isolates and 6% of wildlife isolates
      were indole positive. The remaining isolates from wildlife (33%) and domestic
      animals (30%) were distributed among 53 distinct biovariants. None of these
      individual biovariants represented >4% of the total isolates. Phenotypic
      characterization was valuable for distinguishing between isolates from different
      hosts and from different geographic areas and can be used to assist in
      epidemiologic studies.

PMID- 9526861
TI  - Detection of human granulocytic ehrlichiosis agent and Borrelia burgdorferi in
      ticks by polymerase chain reaction.
AB  - Adult ixodid ticks were collected from Westchester County, New York, and Ipswich,
      Massachusetts, to determine the presence of infection with a human granulocytic
      ehrlichiosis (HGE) agent by using the polymerase chain reaction (PCR). The
      presence of Borrelia burgdorferi in ticks collected from New York was also
      determined by PCR. Of the 229 ticks from New York and 47 ticks from
      Massachusetts, 9% (22/229) and 25% (12/47) of ticks contained HGE agent,
      respectively. Fifty-four percent (123/229) of the ticks collected from New York
      were B. burgdorferi positive; 4% (9/229) of these ticks contained both HGE agent
      and B. burgdorferi. This finding indicates that animals with Lyme borreliosis may
      be also exposed to the etiologic agent of HGE. More extensive laboratory
      diagnosis may be necessary when multiple tick-borne diseases are suspected in
      animals.

PMID- 9526862
TI  - Comparison of the membrane-filtration fluorescent antibody test, the enzyme
      linked immunosorbent assay, and the polymerase chain reaction to detect
      Renibacterium salmoninarum in salmonid ovarian fluid.
AB  - Ovarian fluid samples from naturally infected chinook salmon (Oncorhynchus
      tshawytscha) were examined for the presence of Renibacterium salmoninarum by the
      membrane-filtration fluorescent antibody test (MF-FAT), an antigen capture enzyme
      linked immunosorbent assay (ELISA), and a nested polymerase chain reaction (PCR).
      On the basis of the MF-FAT, 64% (66/103) samples contained detectable levels of
      R. salmoninarum cells. Among the positive fish, the R. salmoninarum
      concentrations ranged from 25 cells/ml to 4.3 x 10(9) cells/ml. A soluble
      antigenic fraction of R. salmoninarum was detected in 39% of the fish (40/103) by
      the ELISA. The ELISA is considered one of the most sensitive detection methods
      for bacterial kidney disease in tissues, yet it did not detect R. salmoninarum
      antigen consistently at bacterial cell concentrations below about 1.3 x 10(4)
      cells/ml according to the MF-FAT counts. When total DNA was extracted and tested
      in a nested PCR designed to amplify a 320-base-pair region of the gene encoding a
      soluble 57-kD protein of R. salmoninarum, 100% of the 100 samples tested were
      positive. The results provided strong evidence that R. salmoninarum may be
      present in ovarian fluids thought to be free of the bacterium on the basis of
      standard diagnostic methods.

PMID- 9526863
TI  - Papillomatous digital dermatitis (footwarts) in California dairy cattle: clinical
      and gross pathologic findings.
AB  - Clinical, gross pathologic, and therapeutic studies were performed on a
      contagious, painful, wart-like digital disease of unknown etiology in California
      dairy cattle. The disease was called papillomatous digital dermatitis (PDD).
      Survey indicated that the disease spread geographically throughout southern
      California over the past few years. In 1991, 31% of herds had papillomatous
      digital dermatitis, whereas in 1994, 89% were affected. Increased incidence
      occurred during late spring and summer, 1-3 months after the rainy season. Within
      herd morbidity ranged from 0.5% to 12% per month. Study of 93 cows in 10 drylot
      dairies revealed that 91% had characteristic circumscribed, erosive to
      papillomatous, intensely painful lesions often surrounded by a ridge of
      hyperkeratotic skin bearing hypertrophied hairs. Lesions were 2-6 cm across
      (88%), circular to oval (78%), and raised (59%) and had surfaces that were
      uniformly erosive and granular (31%), uniformly papillary (28%), or composites of
      both appearances (41%). Lesions were most frequently seen in lactating heifers
      (31%) and 3-year-old cows (43%). Clinical signs were characterized by lameness,
      with walking on toes and clubbing of hooves. Lesions exclusively involved the
      hind limbs in 82% of cows and the plantar/palmar regions in 84% of cows. Lesions
      had high (89%) prediliction for plantar/palmar skin bordering the interdigital
      space. Lesions exclusively involved either the medial or lateral digit in 10% and
      28% of cows, respectively. In 50% of cows, both medial and lateral digits of
      individual limbs were involved; in most cows (31%), lesions apposed each other
      across the plantar interdigital space, whereas in others (19%), lesions
      confluently involved the entire plantar/palmar commissural skin folds. In another
      12% of cows, lesions were axial. High proportions of lesions showed complete
      therapeutic responses to antibiotics: parenteral penicillin (9/9) and ceftiofur
      (41/44), and topical oxytetracycline (4/4). Recurrence or new lesion development
      occurred in 48% of cows reexamined 7-12 weeks after complete therapeutic response
      was observed. Overall, the findings indicated that PDD is a distinct disease
      entity of economic importance in which bacteria may play an important pathogenic
      role.

PMID- 9526864
TI  - Cantharidin poisoning of emu chicks by ingestion of Pyrota insulata.

PMID- 9526865
TI  - Pulmonary metastasis of a feline vaccination-site fibrosarcoma.

PMID- 9526866
TI  - Probable elaeophorosis in a moose (Alces alces) from eastern Washington state.

PMID- 9526867
TI  - Development of a serum plate agglutination test to detect antibodies to
      Ornithobacterium rhinotracheale.

PMID- 9526868
TI  - Disseminated Actinomyces pyogenes infection in a free-ranging white-tailed deer.

PMID- 9526869
TI  - Diagnosis of tuberculosis in two snow leopards using polymerase chain reaction.

PMID- 9526870
TI  - Correlation of genomic detection of feline coronavirus with various diagnostic
      assays for feline infectious peritonitis.

PMID- 9526871
TI  - Adenovirus infection in Spanish ibex.

PMID- 9526872
TI  - Mast cell tumor in an eastern kingsnake (Lampropeltis getulus getulus).

PMID- 9526873
TI  - Typhlocolitis caused by Clostridium difficile in suckling piglets.

PMID- 9526875
TI  - Dioctophyma renale in ranch mink.

PMID- 9526874
TI  - Pseudocytoplasmic inclusions in tongue epithelium of dogs with canine parvovirus
      2 infections.

PMID- 9526876
TI  - A poorly differentiated gastric carcinoid in a dog.

PMID- 9526877
TI  - Rupture of pectoralis major during parallel bar dips: case report and review.
AB  - Rupture of the pectoralis major muscle is an uncommon athletic injury that can
      result in both functional and cosmetic deficiency. To date, most ruptures
      occurring in athletes have occurred while performing bench press or overhead
      lifting maneuvers. We describe a case of a pectoralis major rupture occurring
      while performing weighted parallel bar dips. Despite the popularity of this
      exercise, injuries associated with this exercise are infrequently reported. This
      injury can be easily detected by having the patient perform specific maneuvers on
      physical examination to accentuate any defect that may be present. In most cases,
      this injury is surgically repaired, although conservative treatment can be a
      successful option. Treatment options are discussed and recommendations given. A
      partial or complete tear of the pectoralis major muscle is a rare event and is
      often not easily detected on physical examination. Surgical repair is currently
      recommended to restore previous levels of strength and to correct the resulting
      cosmetic defect. Repair is rarely necessary to perform the normal activities of
      daily living.

PMID- 9526878
TI  - Exercise tolerance in heart transplant patients with altered pulmonary diffusion
      capacity.
AB  - To test whether orthotopic heart transplant (OHT) patients with low pulmonary
      diffusion capacity have a greater limitation to exercise than OHT patients with
      normal pulmonary diffusion capacity, we investigated cardiorespiratory responses
      and blood gases in two groups of OHT patients, one with low (LdG) and the other
      with normal pulmonary diffusion capacity (NdG), during a graded exercise test.
      The results showed 1) significantly reduced peak power (P < 0.05), peak oxygen
      uptake (VO2, P < 0.001), peak oxygen pulse (VO2/heart rate, P < 0.01), peak
      minute ventilation (VE, P < 0.05), and delta PaO2 (peak PaO2 - rest PaO2, P <
      0.05) in LdG versus NdG; 2) a nonsignificant decrease in peak heart rate in LdG
      (P < 0.13, P = 24%); and 3) significant increases in peak respiratory equivalent
      for oxygen (VE/VO2, P < 0.05) and delta P(A-a)O2 (peak P(A-a)O2 - resting P(A
      a)O2, P < 0.05) in LdG versus NdG. No significant difference was found for PaO2
      and PaCO2 at rest or at peak exercise between the groups. A strong correlation
      was found between pulmonary diffusion capacity (TLCO/VA) and peak VO2 (r = 0.81,
      P < 0.01); that is, TLCO/VA explains 66% of the variance in peak VO2. We conclude
      that OHT patients with decreased pulmonary diffusion capacity have a lower
      exercise tolerance than patients with normal pulmonary diffusion capacity.
      However, because of the lack of exercise-induced hypoxemia, diffusion
      abnormalities are not the main limiting factor for exercise tolerance in the low
      diffusion group.

PMID- 9526879
TI  - 12-month Tai Chi training in the elderly: its effect on health fitness.
AB  - PURPOSE: The objective of this study was to evaluate the effect of Tai Chi Chuan
      (TCC) on health fitness in older individuals. METHODS: Thirty-eight community
      dwelling persons aged 58 to 70 yr completed this study. The TCC group included 9
      men and 11 women; the control group included 9 men and 9 women. The TCC group
      practiced TCC for 11.2+/-1.4 months, with the attendance of 4.6+/-1.3 times x wk(
      1). Each session included 20 min of warm-up, 24 min of TCC practice, and 10 min
      of cooldown. The exercise intensity was 52-63% of the heart rate range.
      Cardiorespiratory function, strength, flexibility, and percent of body fat were
      evaluated before and at the end of this study. RESULTS: The male TCC group showed
      16.1% increase in VO2max (P < 0.01), 11 degrees increase in thoracic/lumbar
      flexibility (P < 0.05), 18.1% increase in muscle strength of knee extensor (P <
      0.01), and 15.4% increase of knee flexor (P < 0.05). The female TCC group showed
      21.3% increase in VO2max (P < 0.01), 8.8 degrees increase in flexibility (P <
      0.05), 20.3% increase in muscle strength of knee extensor (P < 0.05), and 15.9%
      increase of knee flexor (P < 0.05). The control group showed no significant
      change in these variables. CONCLUSIONS: The results indicate that a 12-month Tai
      Chi Chuan program is effective for improving health fitness of the elderly.

PMID- 9526880
TI  - Exercise training-induced adaptations in the coronary circulation.
AB  - Aerobic exercise training induces an increase in coronary blood flow capacity
      that is associated with altered control of coronary vascular resistance and,
      therefore, coronary blood flow. The relative importance of metabolic, myogenic,
      endothelium-mediated, and neurohumoral control systems varies throughout the
      coronary arterial tree, and these control systems contribute in parallel to
      regulating coronary vascular resistance to differing degrees at each level in the
      coronary arterial tree. In addition to this nonuniformity of the relative
      importance of vascular control systems in the coronary arterial tree, it appears
      that exercise training-induced adaptations are also distributed spatially, in a
      nonuniform manner throughout the coronary tree. As a result, it is necessary to
      examine training-induced adaptations throughout the coronary arterial tree.
      Adaptations in endothelium-mediated control play a role in training-induced
      changes in control of coronary vascular resistance, and there is evidence that
      the effects of training may be different in large coronary arteries than in the
      microcirculation. Also, there is evidence that the mode, frequency, and intensity
      of exercise training bouts and duration of training may influence the adaptive
      changes in endothelial function. Exercise training has also been shown to induce
      changes in responses of coronary vascular smooth muscle to vasoactive agents and
      alterations in the cellular-molecular control of intracellular Ca2+ in coronary
      vascular smooth muscle of conduit coronary arteries and to enhance myogenic
      reactivity of coronary resistance arteries. Exercise training also appears to
      have different effects on vascular smooth muscle in large coronary arteries than
      in the microcirculation. For example, adenosine sensitivity is increased in
      conduit coronary arteries and large resistance arteries after training but is not
      altered in small coronary resistance arteries of trained animals. Although much
      remains to be studied, evidence clearly indicates that chronic exercise alters
      the phenotype of coronary endothelial and vascular smooth muscle cells and that
      plasticity of these cells plays a role in adaptation of the cardiovascular system
      in exercise training.

PMID- 9526881
TI  - Differential effects of training on the control of skeletal muscle perfusion.
AB  - Endurance and high-intensity sprint training have been shown to alter skeletal
      muscle blood flow and factors that govern muscle perfusion under various
      conditions. Neither endurance nor sprint training alter skeletal muscle perfusion
      at rest but can result in an increase in muscle blood flow during the
      anticipation of exercise. The magnitude of the anticipatory increases in muscle
      blood flow is dependent on the intensity and duration of the prior training bouts
      and results from elevations in mean arterial pressure and decreases in vascular
      resistance in skeletal muscle. The decrements in skeletal muscle vascular
      resistance appear to be mediated through increases in muscle sympathetic
      cholinergic nerve activity or decreases in muscle sympathetic adrenergic nerve
      activity. During submaximal exercise, total muscle blood flow is either unchanged
      or slightly lower. However, a redistribution of muscle blood flow may occur
      following aerobic training, resulting in an enhanced perfusion of high-oxidative
      skeletal muscles and less flow going to low-oxidative muscles. The increased
      perfusion of the high-oxidative muscles may result from various factors
      including: a) increased recruitment of high-oxidative motor units, b) increased
      local release of metabolic vasodilator substances, c) qualitative changes in the
      metabolic substances released, d) decreased muscle sympathetic nerve activity, e)
      diminished sensitivity of the arterial vasculature to norepinephrine or other
      vasoconstrictor agents, f) enhanced endothelium-mediated dilation in the
      resistance vasculature, and g) an increased effectiveness of the skeletal muscle
      pump. Conversely, the decreases in blood flow to low-oxidative muscles may result
      from an enhanced autoregulatory responsiveness of the resistance vasculature.
      Endurance and sprint training increase muscle perfusion during exercise at
      VO2max: this primarily appears to be the result of an enhanced pumping capacity
      of the heart to increase in maximal cardiac output. Many of the training-induced
      alterations in muscle blood flow and vascular structure are localized in the
      muscles that are most active during the training bouts. Therefore, differences in
      muscle recruitment patterns that occur with low-intensity endurance exercise and
      high-intensity sprint exercise may account for differences observed between these
      two training regimens.

PMID- 9526883
TI  - Physical training and the control of skin blood flow.
AB  - The process of physical training places frequent significant demands for
      increased blood flow to cardiac and skeletal muscle tissues and sets into action
      adaptive responses to better enable the circulatory system to meet those demands.
      These adaptive changes and the associated mechanisms are dealt with elegantly in
      other portions of this symposium. The repeated bouts of dynamic exercise with
      training also expose the temperature regulatory system to increased body
      temperatures and attendant demands for increased heat loss. These frequent
      demands for increased heat loss lead to adaptations in the control of the
      cutaneous circulation. There are consistent results among the limited number of
      studies conducted to test this question directly. The primary result is that skin
      blood flow in the trained state is higher at a given level of internal
      temperature than in the sedentary or less trained state. This result is seen in
      both cross-sectional and longitudinal comparisons, in older and younger subjects,
      in responses to heat at rest and during exercise, and in the changes with
      detraining as well as those attending training. In some studies this adjustment
      is made by a shift in the threshold internal temperature at which skin blood flow
      begins to rise, whereas in others it is accomplished by an increase in the
      sensitivity of the skin blood flow-internal temperature relationship. Reasons for
      this variation are not clear. The cutaneous circulation is controlled by
      vasoconstrictor and separate vasodilator nerves, but it is not clear how much of
      the training effect is manifest through one or the other neural system. However,
      indirect data suggest that vasoconstrictor activity is generally reduced and that
      active vasodilator activity is initiated at lower internal temperatures. It is
      also not clear to what extent the mechanism for the training effect is through
      the acclimatization process, as opposed to the influence of training, itself. In
      any case, the adjustments in control of the cutaneous circulation with physical
      training increase the capacity of the circulation to transport and eliminate heat
      as that training process increases the capacity of the active tissues to produce
      that heat.

PMID- 9526882
TI  - Adaptations in control of blood flow with training: splanchnic and renal blood
      flows.
AB  - Acute exercise is associated with large increases in cardiac and active skeletal
      muscle blood flows and reduced blood flows to inactive muscle, skin, kidneys, and
      organs served by the splanchnic circulation. Splanchnic and renal blood flows are
      reduced in proportion to relative exercise intensity. Increased sympathetic
      nervous system outflow to splanchnic and renal vasculature appears to be the
      primary mediator of reduced blood flows in these circulations, but the
      vasoconstrictors angiotensin II and vasopressin also make important
      contributions. Human and animal studies have shown that splanchnic and renal
      blood flows are reduced less from resting levels during acute exercise after a
      period of endurance exercise training. Investigations of mechanisms involved in
      these adaptations suggest that reductions in sympathetic nervous system outflow,
      and plasma angiotensin II and vasopressin concentrations, are involved in lesser
      splanchnic and renal vasoconstriction exhibited by trained individuals. In
      addition, a reduced response to the sympathetic neurotransmitter norepinephrine
      in renal vasculature may contribute to greater blood flow to the kidney during
      acute exercise after training. Greater splanchnic and renal blood flows during
      acute exercise following training are potentially beneficial in that disturbance
      from homeostasis would be less in the trained state. Additionally, increased
      splanchnic blood flow in the trained state may confer benefits for glucose
      metabolism during prolonged exercise.

PMID- 9526884
TI  - Sympathetic neural adaptations to exercise training in humans: insights from
      microneurography.
AB  - Sympathetic nerve activity has long been regarded as an important regulator of
      blood flow and blood pressure. Its importance has been especially recognized
      during exercise. The present review examines sympathetic neural adaptations to
      exercise training in humans obtained by sympathetic nerve recordings to nonactive
      skeletal muscle. Little evidence exists from both cross-sectional and
      longitudinal studies indicating that training alters resting muscle sympathetic
      nerve activity (MSNA). However, MSNA responses during exercise appear to be
      attenuated after training. This attenuation of MSNA seems to be specific to the
      trained muscle and not generalizable to other muscle groups. The mechanisms for
      the decrease in exercise-induced MSNA have been attributed to changes in both the
      muscle metaboreflex and muscle mechanoreflex. In addition to exercise, training
      has generally not altered MSNA responses to other stressors such as cold pressor
      test, lower body negative pressure, and upright tilting. However, the effect of
      training on baroreflex control of MSNA is equivocal. These conclusions are based
      on few studies. More comprehensive training studies are needed to better
      understand the role of training on sympathetic neural outflow.

PMID- 9526885
TI  - The biological basis of physical activity.
AB  - Successful efforts to improve levels of physical activity in the population are
      contingent upon an accurate understanding of the determinants of habitual
      activity. While most research has focused on psychosocial and environmental
      influences, the potential effect of intrinsic biological control on regular
      activity has received little attention. This review examines evidence for the
      existence of such central control, offers a rationale for its function, and
      suggests implications for preventive health strategies resulting from a
      biological contribution to habitual activity levels.

PMID- 9526886
TI  - Potential effects of maternal physical activity on birth weight: brief review.
AB  - This review lists the most commonly accepted risk factors for low birth weight
      (LBW) and offers critical examination of research on the effect of maternal
      physical activity, both occupational and leisure time, on birth weight. Some
      studies have shown job related physical "activity" to be related to unfavorable
      birth outcomes, including premature delivery and LBW. However, most studies have
      not controlled for socioeconomic status, nor has actual physical activity been
      well quantified throughout gestation. Similarly, results of the relationship
      between leisure time physical activity and birth weight are mixed. Current
      evidence appears to indicate participation in moderate to vigorous activity
      throughout pregnancy may enhance birth weight, while more severe regimens may
      result in lighter offspring. Careful quantification of caloric balance during
      pregnancy in chronic exercisers is needed before further conclusions can be
      drawn. Indeed, the interaction between energy expenditure (whether job related or
      leisure time) and caloric consumption must be addressed to determine whether
      physical activity per se may affect birth outcome, or if it is merely a
      confounder. Future studies should include randomized trials in which women
      without a history of chronic physical activity are assigned to either an
      exercise/physical activity or control group.

PMID- 9526887
TI  - Impaired pituitary hormonal response to exhaustive exercise in overtrained
      endurance athletes.
AB  - The aim of the present prospective longitudinal study was to investigate the
      hormonal response in overtrained athletes at rest and during exercise consisting
      of a short-term exhaustive endurance test on a cycle ergometer at an intensity
      10% above the individual anaerobic threshold. Over a period of 19+/-1 months, 17
      male endurance athletes (cyclists and triathletes; age 23.4+/-1.6 yr; VO2max.
      61.2+/-1.8 mL x min(-1) x kg(-1); means+/-SEM) were examined five times on two
      separate days under standardized conditions. Short-term overtraining states (OT,
      N=15) were primarily induced by an increase of frequency of high-intensive bouts
      of exercise or competitions without increase of the total amount of training. OT
      was compared with normal training states intraindividually (NS, N=62). During OT,
      the time to exhaustion of the exercise test was significantly decreased by 27% on
      average. At rest and during exercise, the concentrations in plasma and the
      nocturnal excretion in urine of free epinephrine and norepinephrine were not
      significantly changed during OT. At physical rest, the concentrations of (free)
      testosterone, cortisol, luteinizing hormone, follicle-stimulating hormone,
      adrenocorticotropic hormone, growth hormone, and insulin during OT were
      comparable with those during NS. A significantly (P < 0.025) lower maximal
      exercise-induced increase of the adrenocorticotropic hormone and growth hormone,
      as well as a trend for a decrease of cortisol (P=0.060) and insulin (P=0.036),
      was measured. The response of free catecholamines as well as the ergometric
      performance of an all-out 30-s test was unchanged. Serum urea, uric acid,
      ferritin, and activity of creatine kinase showed no differences between
      conditions. In conclusion, the results confirm the hypothesis of a hypothalamo
      pituitary dysregulation during OT expressed by an impaired response of pituitary
      hormones to exhaustive short-endurance exercise.

PMID- 9526888
TI  - Muscle damage induced by stretch-shortening cycle exercise.
AB  - PURPOSE: Strenuous stretch-shortening cycle exercise was used as a model to study
      the leakage of proteins from skeletal muscle. METHODS: The analysis included
      serum levels of creatine kinase (S-CK), myoglobin (S-Mb), and carbonic anhydrase
      (S-CA III). Blood samples from power- (N=11) and endurance-trained (N=10)
      athletes were collected before, 0, and 2 h after the exercise, which consisted of
      a total of 400 jumps. RESULTS: The levels of all determined myocellular proteins
      increased immediately after the exercise (P < 0.05-0.001) among both subject
      groups. In the endurance group, the protein levels increased (P < 0.05-0.001)
      further during the following 2 h after the exercise, and the ratio of S-CA III
      and S-Mb decreased (P < 0.05) in a before-after comparison. This was not the case
      among the power group despite their greater mechanical work (P < 0.001) and
      higher ratio of eccentric and concentric EMG activity of the leg extensor muscles
      (P < 0.05). CONCLUSIONS: The differences of the determined protein levels between
      the subject groups might be due to obvious differences in the muscle fiber
      distribution, differences in recruitment order of motor units, and/or differences
      in training background.

PMID- 9526889
TI  - Dithiothreitol improves recovery from in vitro diaphragm fatigue.
AB  - There is increasing evidence that reactive oxygen species are produced during
      strenuous skeletal muscle work and that they contribute to the development of
      muscle fatigue. Although the precise cellular mechanisms underlying such a
      phenomenon remain obscure, it has been hypothesized that endogenously produced
      reactive oxygen species may down-regulate force production during fatigue by
      oxidizing critical sulfhydryl groups on important contractile proteins. To test
      this hypothesis, we fatigued rat diaphragm strips in vitro for 4 min at 20 Hz
      stimulation and a duty cycle of 0.33. Following fatigue, the tissue baths were
      drained and randomly replaced with either physiologic saline or physiologic
      saline containing the disulfide reducing agent, dithiothreitol (DTT) at varying
      doses (0.1-5.0 mM). Force-frequency characteristics were then measured over a 90
      min recovery period. At the 0.5 and 1.0 mM doses, DTT treatment was associated
      with significantly greater force production in the recovery period. DTT's effects
      were observed at most frequencies tested, but appeared more prominent at the
      higher frequencies. The beneficial effects of DTT were not evident at the 0.1 or
      5.0 mM doses and appeared to be specific for fatigued muscle. These recovery
      enhancing effects of a potent disulfide reducing agent suggest that important
      contractile proteins may be oxidized during fatigue; such changes may be readily
      reversible.

PMID- 9526890
TI  - Seven-year change in graded exercise treadmill test performance in young adults
      in the CARDIA study. Cardiovascular Risk Factors in Young Adults.
AB  - PURPOSE: Most studies of physical fitness change have been relatively small, not
      population-based, and lacking in women and nonwhites. The purpose of this
      analysis was to evaluate the 7-yr change in physical fitness in a biracial (black
      and white) population of young men and women. METHODS: We evaluated change in
      exercise treadmill test performance in a biracial (black and white) population of
      1,962 young adults, ages 18-30 yr at baseline, who completed symptom-limited
      graded exercise treadmill tests at the baseline (1985-1986) and year 7 (1992
      1993) examinations of the CARDIA study. RESULTS: Mean test duration decreased 58
      s (9.5%) over 7 yr (black men, 13.6% decrease, white men, 7.4%; black women,
      11.1%; white women, 7.0%). Mean time to heart rate 130 (WL130), a measure of
      submaximal performance, decreased 31 s (11.3%) (black men, 16.9%; white men,
      10.0%; black women, 12.3%; white women, 6.1%). Baseline body mass index (BMI) and
      physical activity were not statistically significant predictors of test duration
      change in any race-gender group, but change in BMI and activity were. Seven-year
      weight gain >20 lbs (31% of cohort) was associated with a large decrease in
      fitness (18.5% decrease in mean duration, 21.8% decrease in WL130). CONCLUSION:
      These data suggest that fitness declines during young adulthood in blacks and
      whites and that fitness changes are related to changes in weight and physical
      activity.

PMID- 9526891
TI  - Physical fitness related to age and physical activity in older persons.
AB  - OBJECTIVE: This study investigated physical fitness as a function of age and
      leisure time physical activity (LTPA) in a community-based sample of 624 persons
      aged 57 yr and older. METHODS: LTPA during the last 12 months was assessed
      through personal interviews. A wide range of physical fitness components was
      measured using performance-based tests. RESULTS: Physical fitness was associated
      with the interaction age by LTPA in only a few components, in a gender-specific
      way, with generally larger differences in fitness between active and less active
      persons with increasing age. All LTPA, including low intensity LTPA, is
      positively and age-independent associated with most physical fitness components.
      CONCLUSION: The importance of LTPA typically participated in by the general
      population lies not so much in the delaying of the motor aging process but rather
      in a general, age-independent, positive effect.

PMID- 9526892
TI  - Neuromuscular, metabolic, and kinetic adaptations for skilled pedaling
      performance in cyclists.
AB  - PURPOSE: The purpose of this study was to clarify the reason for the difference
      in the preferred cadence between cyclists and noncyclists. METHODS: Male cyclists
      and noncyclists were evaluated in terms of pedal force, neuromuscular activity
      for lower extremities, and oxygen consumption among the cadence manipulation (45,
      60, 75, 90, and 105 rpm) during pedaling at 150 and 200 W. Noncyclists having the
      same levels of aerobic and anaerobic capacity as cyclists were chosen from
      athletes of different sports to avoid any confounding effect from similar kinetic
      properties of cyclists for lower extremities (i.e., high speed contraction and
      high repetitions in prolonged exercise) on both pedaling performance and
      preferred cadence. RESULTS: The peak pedal force significantly decreased with
      increasing of cadence in both groups, and the value for noncyclists was
      significantly higher than that for cyclists at each cadence despite the same
      power output. The normalized iEMG for vastus lateralis and vastus medialis
      muscles increased in noncyclists with rising cadence; however, cyclists did not
      show such a significant increase of the normalized iEMG for the muscles. On the
      other hand, the normalized iEMG for biceps femoris muscle showed a significant
      increase in cyclists while there was no increase for noncyclists. Oxygen
      consumption for cyclists was significantly lower than that for noncyclists at 105
      rpm for 150 W work and at 75, 90, and 105 rpm for 200 W work. CONCLUSIONS: We
      conclude that cyclists have a certain pedaling skill regarding the positive
      utilization for knee flexors up to the higher cadences, which would contribute to
      a decrease in peak pedal force and which would alleviate muscle activity for the
      knee extensors. We speculated that pedaling skills that decrease muscle stress
      influence the preferred cadence selection, contributing to recruitment of ST
      muscle fibers with fatigue resistance and high mechanical efficiency despite
      increased oxygen consumption caused by increased repetitions of leg movements.

PMID- 9526893
TI  - Temporal specificity in adaptations to high-intensity exercise training.
AB  - OBJECTIVE: The purpose was to test the hypothesis that time to exhaustion and
      oxygen deficit in high-intensity exercise at a particular time of day would be
      influenced by training regularly at that time of day. METHODS: Over a 5-wk
      period, 12 college-age women performed 20 high-intensity exercise training
      sessions. On Mondays, they performed four 2-min bouts of cycling at 2.5 W x kg(
      1) with 4-min recoveries; on Tuesdays and Thursdays, eight 1-min bouts at 3.0 W x
      kg(-1) with 2-min recoveries; and on Wednesdays, three 3-min bouts at 2.2 W x kg(
      1) with 2-min recoveries. Six participants (a.m.-trained group) were randomly
      assigned to train in the morning (a.m.) and six others (p.m.-trained group)
      trained in the afternoon (p.m.). Upon completion of training, all participants
      were tested in both the a.m. and p.m. (random order) at the same times as
      training sessions had been scheduled. Tests involved exhaustive efforts at 2.6 W
      x kg(-1). RESULTS: Results of a repeated measures ANOVA revealed a significant
      time of day of training x time of day of testing interaction effect on time to
      exhaustion (F1,10=8.29, P=0.02). This suggested that the time of day of training
      affected the a.m.-p.m. pattern in time to exhaustion. Time to exhaustion for the
      a.m.-trained group was 398+/-258 s in the a.m. test and 351+/-216 s in the p.m.
      test (P=0.07). The p.m.-trained group had significantly higher values in the p.m.
      test compared with the a.m. test (422+/-252 s vs 373+/-222 s; P=0.03). There was
      also a significant interaction effect on oxygen deficit (F1,10=8.03, P=0.02).
      This suggested that the time of day of training affected the a.m.-p.m. pattern in
      anaerobic capacity. Oxygen deficit for the a.m.-trained group was 64+/-24 mL x
      kg(-1) in the a.m. test and 50+/-11 mL x kg(-1) in the p.m. test (P=0.10). The
      p.m.-trained group had significantly higher values in the p.m. tests (64+/-24 mL
      x kg(-1) vs 50+/-11 mL x kg(-1); P=0.01) compared to the a.m. tests. CONCLUSIONS:
      These results demonstrate that there is temporal specificity in training to
      increase work capacity in high-intensity exercise. Greater improvements can be
      expected to occur at the time of day at which high-intensity training is
      regularly performed.

PMID- 9526894
TI  - Impact of a fat-rich diet on endurance in man: role of the dietary period.
AB  - OBJECTIVE: The aim of the present study was to evaluate the effect of duration on
      the interaction between training and a fat-rich or a carbohydrate-rich diet on
      endurance performance. METHODS: Fifteen untrained males were randomly assigned to
      consume a fat-rich (T-FAT) or a carbohydrate-rich diet (T-CHO) while following an
      endurance training program. Endurance performance at 80% of pretraining VO2max
      was measured before, after 2 wk, and after 4 wk. RESULTS: Time to exhaustion,
      when exercising at the same absolute workload, was similar in T-FAT and T-CHO at
      all tests and was significantly increased by 166% and 150% in T-FAT and T-CHO,
      respectively, after 4 wk. Maximal oxygen uptake increased by 9% in both groups (P
      < 0.05). After 4 wk, RER was significantly lower during exercise in T-FAT both
      compared with the initial test and with T-CHO, while no changes appeared in T
      CHO. CONCLUSIONS: The present findings showed that endurance performance was
      enhanced similarly after both 2 and 4 wk of adaptation to training and a fat-rich
      or a carbohydrate-rich diet.

PMID- 9526895
TI  - Strength and endurance of elite soccer players.
AB  - PURPOSE: The major purpose of the present study was to examine whether there
      exists a relationship between preseasonal physiological tests and performance
      results in the soccer league. Further, it investigated maximal oxygen uptake and
      maximal strength in proportion to body mass for soccer players. A secondary aim
      was to establish some normative data of Norwegian elite soccer players. METHODS:
      Two teams from the Norwegian elite soccer league participated in the study.
      RESULTS/CONCLUSION: The present study supports previous investigations indicating
      a positive relationship between maximal aerobic capacity, physical strength, and
      performance results in the elite soccer league. It is concluded that for soccer
      players, maximal oxygen uptake should be expressed in relation to body mass
      raised to the power of 0.75 and maximal strength in relation to body mass raised
      to the power of 0.67, when the aim is to evaluate maximal aerobic capacity when
      running and strength capacity among players with different body mass. Midfield
      players had significantly higher maximal oxygen uptake compared with defense
      players using the traditional expression, mL x kg(-1) x min(-1), while no
      significant differences were found expressing maximal oxygen uptake either
      absolutely (L x min[-1]) or in relation to body mass raised to the power of 0.75
      (mL x kg[-0.75] x min[-1]) among players grouped by position. There was a
      significant correlation (r = 0.61, P < 0.01) between squat IRM and vertical jump
      height. Vertical jump heights for defense and forward players were significantly
      higher compared with midfield players. Mean results from the laboratory test were
      63.7 mL x kg(-1) x min(-1) or 188.6 mL x kg[-0.75] x min(-1) for maximal oxygen
      uptake, 150 kg or 8.0 kg x mb(-0.67) for 90 degrees squats, 79.9 kg or 4.4 kg x
      mb(-0.67) for bench press. Mean values of vertical jump height were 54.9 cm.

PMID- 9526896
TI  - Telemetry pill measurement of core temperature in humans during active heating
      and cooling.
AB  - PURPOSE: This study compared the agreement between core temperature measurements
      obtained using an ingestible temperature pill telemetry system (Tpill) with those
      obtained from rectal (Tre) and esophageal (Tes) thermocouples under conditions of
      increasing and decreasing body temperature. METHODS: Four men and five women (age
      25+/-2 yr, BSA 1.81+/-0.05 m2, VO2 peak 3.1+/-0.4 L x min[-1]) participated in
      four 3-h trials: cold (18 degrees C) water rest (CWR), cold water exercise (CWE),
      warm (36 degrees C) water rest (WWR), and warm water exercise (WWE). Subjects
      were immersed to the neck for each trial. During resting trials, subjects sat
      quietly. During exercise trials, subjects completed three bouts of 15 min of
      rest, followed by 45 min of exercise on a cycle ergometer at 50% of peak oxygen
      uptake. The temperature pill was taken 10-12 h before testing, after which the
      subjects fasted. RESULTS: The trials created conditions of constantly decreasing
      (CWR) or increasing (WWR) core temperature, as well as periods of oscillating
      core temperature (CWE and WWE). Root mean squared deviation (RMSD) was calculated
      for each pair of measurements (Tpill vs Tre, Tpill vs Tes, Tre vs Tes) for each
      trial. An RMSD of "0" indicates perfect agreement; as RMSD increases, agreement
      worsens. On CWR, the RMSD for Tpill-Tes (0.23+/-0.04) was lower (P < 0.05) than
      for Tpill-Tre (0.43+/-0.10) or Tre-Tes (0.46+/-0.09). There were no significant
      differences in RMSD between measurement pairs on any other trial (average RMSD =
      0.26 degrees C). Telemetry pill temperature and response time tended to be
      intermediate between Tre and Tes. CONCLUSION: These results suggest the telemetry
      pill system provides a valid measurement of core temperature during conditions of
      decreasing as well as increasing body temperature and during steady state.

PMID- 9526897
TI  - Costs associated with asthma treatment.

PMID- 9526898
TI  - Critical care management of the asthmatic patient.
AB  - The incidence and severity of asthma continue to increase despite advances in
      therapy. Two types of severe asthma exacerbations have been described: "sudden
      onset" and "slow onset." Beta-adrenergic agonists and corticosteroids are still
      the mainstay of therapy in the intensive care unit. Hypercapnic hypoventilation
      is advocated as a mode of mechanical ventilation to maintain oxygenation while
      minimizing barotrauma. Sedating and paralytic agents must be used with caution to
      prevent complications such as myopathy, which may occur with prolonged use of
      these agents. Future avenues of study could include the use of leukotriene and
      platelet-activating factor inhibitors. Asthma management guidelines should be
      practiced to prevent worsening of bronchospasm to the point of severe
      exacerbation.

PMID- 9526899
TI  - Airway involvement in hypersensitivity pneumonitis.
AB  - Exposure to organic particles causes, in a susceptible host, diffuse inflammation
      of the lung acinus. However, immunopathologic response may not be confined to the
      alveoli and may also involve the large and peripheral airways. Therefore, after
      allergen inhalation a clinical spectrum of respiratory disorders may be observed,
      including hypersensitivity pneumonitis, asthma, chronic airway obstruction, and
      simple chronic bronchitis. Hypersensitivity pneumonitis is not a uniform disease
      but a complex syndrome, and the involvement of the airways may occur alone,
      simultaneously with, or after the parenchymal disease.

PMID- 9526900
TI  - Neuropeptides and asthma.
AB  - Although asthma is considered to be an inflammatory disease of the airways,
      neural mechanisms remain very important. Neural control of airways is far more
      complex than has been previously recognized. In addition to the classic neural
      pathways, the nonadrenergic, noncholinergic pathway has been described in the
      airways of animals and humans. Neuropeptides are present in sensory,
      parasympathetic, and sympathetic neurons in airways, and have been shown to have
      proinflammatory effects, such as increased mucus production, microvascular
      leakage, and smooth muscle contraction. Neuropeptides released from sensory
      nerves (eg, neurokinin A and substance P) mediate excitatory nonadrenergic,
      noncholinergic transmission, which causes bronchoconstriction and, possibly,
      bronchial hyperresponsiveness. Better understanding of neural mechanisms might
      provide a useful therapeutic approach in the future.

PMID- 9526902
TI  - Parenteral triamcinolone acetonide: an alternative corticosteroid for the
      treatment of asthma.
AB  - Corticosteroids are effective in reducing the airway inflammation and controlling
      the symptoms of asthma. Many patients with chronic, severe asthma are steroid
      dependent, requiring daily oral corticosteroids. Although corticosteroids may be
      effective, many patients suffer from their intolerable side effects. Various
      medications have been used as steroid-sparing agents in patients who suffer from
      the side effects of long-term high-dose steroids. While drugs like methotrexate
      and cyclosporine are promising, none have clearly been shown to be beneficial in
      most patients with asthma. The long-acting parenteral steroid triamcinolone
      acetonide has been tested by various investigators in these patients for over 20
      years. Intramuscular triamcinolone appears to beneficial, with no significant
      increase in adverse effects.

PMID- 9526901
TI  - The role of antileukotrienes in asthma management.
AB  - The antileukotriene agents are the first new category of asthma medications
      introduced in the past two decades. Leukotriene synthesis inhibitors block the
      production of leukotrienes whereas leukotriene receptor antagonists block the
      effects of leukotrienes at the receptor level. Leukotriene synthesis inhibitors
      are further classified as either 5-lipoxygenase inhibitors or 5-lipoxygenase
      activating protein inhibitors. Zafirlukast, montelukast, and pranlukast are
      leukotriene receptor antagonists whereas zileuton is a 5-lipoxygenase inhibitor.
      Antileukotrienes have been shown to be relatively safe and effective in chronic
      mild to moderate asthma. Studies are ongoing to determine how they compare with
      inhaled steroids, which remain the drug of choice for anti-inflammatory therapy.

PMID- 9526903
TI  - Diagnostic pitfalls in asthma.
AB  - Asthma is a common disease, diagnosed and treated routinely, that still lacks a
      clear, universally accepted definition. The diagnosis, made mostly by history and
      physical diagnosis, is often supported by peak flow rate or spirometric
      measurements. This time-honored approach may prove to be unreliable, resulting in
      overdiagnosis of the disease. The literature is replete with reports about
      patients treated as if they had asthma in whom other pulmonary diseases were
      eventually diagnosed. The incidence of asthma is increasing; there seems to be a
      lower threshold now for making this diagnosis. Overdiagnosis can be avoided,
      however, by systematic evaluation and complete pulmonary function testing. This
      paper presents two examples of clinical carelessness resulting in diagnostic
      delay of underlying disorders mimicking bronchial asthma.

PMID- 9526904
TI  - Panic, dyspnea, and asthma.
AB  - Dyspnea, a cardinal symptom of asthma, is also a common feature of panic attacks.
      Patients with asthma have high rates of anxiety disorders, and respiratory
      illness may be a risk factor in the development of panic disorder. The diagnosis
      of anxiety disorders in patients with asthma can be challenging, but successful
      identification and treatment of anxiety can reduce morbidity and improve quality
      of life in these patients. Serotonergic anxiolytic medications and cognitive
      behavioral therapy appear to be the treatments of choice for pathologic anxiety
      in patients with asthma.

PMID- 9526905
TI  - The genetics of asthma.
AB  - The genetic approach to asthma has revealed a few candidate genes. Among them,
      special attention is given to the association between chromosome 5q and various
      cytokines and also to chromosome 11q and the IgE receptor. A mutation in
      chromosome 5 enhances interleukin-4 activity, which increases IgE synthesis by
      plasma cells. Polymorphism in the beta chain of the high-affinity IgE receptor
      (FC epsilonRI-beta) is considered to play a key role in the pathogenesis of
      asthma. Increased IgE, caused by both mutations, is responsible for inflammatory
      allergic reactions. A possible link between genetics and asthma has been
      suggested, although some studies could not confirm an association. Further study
      of the candidate genes may allow at-risk individuals to be tested and new
      treatments to be developed.

PMID- 9526906
TI  - Chicago Asthma Consortium.
AB  - The Chicago Asthma Consortium is a group that oversees and attempts to improve
      the outcomes for the asthmatic population of the city of Chicago and is designed
      to respond to the perceived needs of this community. It has more than 300 members
      who operate through six standing committees and in its first year of operation,
      the Chicago Asthma Consortium has seen notable successes, such as the effecting
      of a change in a restrictive policy on medication use by students in the Chicago
      public schools. We describe here the details of the function of the Chicago
      Asthma Consortium and give examples of its effectiveness in dealing with this
      common, yet complex, disease.

PMID- 9526907
TI  - Upper airways involvement in bronchial asthma.
AB  - The upper airways--the nose, pharynx, and mouth--lead through the larynx and into
      the tracheobronchial tree of the lung (the lower airways). This cavernous void in
      the upper airways transports external air to the alveolar sacs, in the distal
      segments of the tracheobronchial tree. Oxygen is absorbed from the alveolar sacs
      and carbon dioxide is released. Yet, under adverse physiologic conditions such as
      allergic or nonallergic rhinitis, sinusitis, and bronchitis, obstruction of the
      upper and lower airways occurs and leads to sneezing, rhinitis, and bronchospasm.
      The simultaneous occurrence of upper airways disease and asthma is addressed in
      this review.

PMID- 9526908
TI  - The clinical effects of nifedipine on periodontal status.
AB  - The present study was conducted to determine the clinical effects of nifedipine
      on the gingiva of 97 patients. Patients were examined for changes in periodontal
      status and divided into subgroups, based on their age, gender, duration of drug
      intake, presence/absence of plaque and gingival inflammation, and according to
      the presence and severity of gingival overgrowth. Gingival overgrowth was noticed
      in 29% of the patients. Among the recorded parameters, duration of drug intake,
      presence/severity of gingival inflammation, and gender seemed to have the
      greatest effect on the development of gingival overgrowth. Patients with higher
      gingival inflammation scores, those on nifedipine medication for more than 4
      years, and males were likely to have an increased tendency for higher incidence
      and severity of gingival overgrowth. The findings of the present study suggest
      that nifedipine medication induces gingival overgrowth and that certain local
      factors are involved in the pathogenesis of drug-induced gingival overgrowth.
      However, individual ability and sensitivity to metabolize the drug and its
      metabolites also seem to be important etiological factors.

PMID- 9526909
TI  - Diabetes prevents periodontitis-induced increases in gingival platelet derived
      growth factor-B and interleukin 1-beta in a rat model.
AB  - Periodontitis is a chronic inflammatory disease characterized by a progression
      that is very much dependent on host response. The gingiva can be considered to be
      in a constant state of wounding (pathologic wounding by bacterial plaque) and a
      constant state of maintenance/repair. In this context, any metabolic disturbance
      in the host which compromises tissue repair/wound healing will exacerbate the
      progression of periodontitis. Diabetes presents an interesting example because
      two major complications of diabetes are delayed wound healing and periodontitis.
      Our previous studies indicate that delayed wound healing and periodontitis may be
      manifestations of a general systemic deficit in diabetes involving alteration of
      macrophage cytokine gene expression. The present study was designed to determine
      whether: 1) diabetes-induced metabolic alterations affect gingival cytokine
      levels; and 2) diabetes-induced metabolic alterations modify the gingival
      cytokine profile in periodontitis. Sprague-Dawley rats (N=12/group) were injected
      with streptozotocin (65 mg/kg) into the tail vein to induce diabetes (defined by
      blood glucose levels > 250 mg/dl) or received the injection vehicle or no
      treatment as controls. Periodontitis was induced in additional groups of diabetic
      and control rats by gavage with Porphyromonas gingivalis A7436. After 90 days,
      serum glucose was analyzed to document diabetes; alveolar bone level was measured
      to document severity of periodontitis; gingiva was harvested circumferentially
      from the first and second molars; and cytokines in gingival homogenates were
      assayed by ELISA using commercial kits. Cytokine levels were expressed as mean+/
      SEM pg/microg protein. Diabetes alone did not alter the gingival cytokine profile
      for platelet-derived growth factor B (PDGF-B), interleukin 1-beta (IL-1beta),
      transforming growth factor-beta (TGF-beta), and tumor necrosis factor-alpha (TNF
      alpha). Periodontitis alone demonstrated a significant increase (P < 0.05) in
      levels of PDGF-B and IL-1beta. Diabetes superimposed on periodontitis prevented
      these increases. Thus, diabetes-induced metabolic alterations do not affect
      gingival cytokine levels per se; however, they do alter the normal host response
      to periodontitis through blockage of periodontitis-induced increases in PDGF-B
      and IL-1beta.

PMID- 9526910
TI  - Periodontal status and subgingival microbiota of insulin-dependent juvenile
      diabetics: a 3-year longitudinal study.
AB  - This study examined for 3 years the changes in periodontal status and the
      possible correlations with selected subgingival microbiota and diabetic
      conditions in a group of 16 insulin-dependent diabetes mellitus (IDDM, JD)
      patients as compared with their 16 healthy cohabiting siblings (HS). JD patients
      were monitored every 3 months for levels of glycosylated hemoglobin (HbA1C).
      Clinical and microbiological parameters were measured 6 weeks before drawing
      blood to determine levels of HbA1C. Periodontal parameters were measured at
      baseline (TO), year 2 (T2), year 3 (T3) and included: probing depth (PD),
      attachment level (AL), sulcus bleeding index (SBI), and plaque index (PI). Two
      sites in each patient were selected for microbial samples: a mesio-facial aspect
      of the maxillary right first molar (defined as constant site, CS) and a site with
      the greatest probing depth (defined as deepest site, DS). Microbial samples were
      analyzed by culture techniques. No significant differences in clinical parameters
      were found between diabetics and healthy siblings at any examination. The SBI in
      the non-diabetic group at T2 and at T3 was significantly lower than at baseline.
      PD and AL of constant sites in the diabetic group at T3 were significantly higher
      than baseline. There was a significant increase in Prevotella intermedia at T3 as
      compared with baseline for deepest sites in the diabetic group. Cluster analysis
      revealed, in a former study, two clusters (IV and V) at baseline which were
      significantly different from the overall mean regarding composition of
      Porphyromonas gingivalis and Capnocytophaga spp. They were not significantly
      different for periodontal parameters from TO to T3. These data would suggest no
      significant differences in clinical parameters between the diabetics and non
      diabetic siblings throughout this 3-year longitudinal study.

PMID- 9526911
TI  - Recombinant human osteogenic protein-1 (OP-1) stimulates periodontal wound
      healing in class III furcation defects.
AB  - Osteogenic protein-1 (OP-1) is a member of the transforming growth factor beta
      superfamily and is a potent modulator of osteogenesis and bone cell
      differentiation. This preclinical study in dogs sought to assess the effects of
      OP-1 on periodontal wound healing in surgically created critical size Class III
      furcation defects. Eighteen male beagle dogs were subjected to the creation of
      bilateral mandibular 5 mm osseous defects. A split-mouth design was utilized
      which randomly assigned opposing quadrants to control therapy (surgery alone or
      collagen vehicle) or 1 of 3 ascending concentrations of OP-1 in a collagen
      vehicle (0.75 mg OP-1/g collagen, 2.5 mg/g, or 7.5 mg/g). Thus, 9 quadrants per
      test group received OP-1, 9 quadrants per control group received surgery alone,
      and 9 quadrants received collagen vehicle alone. Test articles were delivered by
      a surgeon masked to the treatment, and fluorogenic bone labels were injected at
      specified intervals post-treatment. Eight weeks after defect creation and OP-1
      delivery, tissue blocks of the mandibulae were taken for masked histomorphometric
      analysis to assess parameters of periodontal regeneration (e.g., bone height,
      bone area, new attachment formation, and percent of defect filled with new bone).
      Histomorphometry revealed limited evidence of osteogenesis, cementogenesis, and
      new attachment formation in either vehicle or surgery-alone sites. In contrast,
      sites treated with all 3 concentrations of OP-1 showed pronounced stimulation of
      osteogenesis, regenerative cementum, and new attachment formation. Lesions
      treated with 7.5 mg/g of OP-1 in collagen regenerated 3.9+/-1.7 mm and 6.1+/-3.4
      mm2 (mean +/-S.D.) of linear bone height and bone area, respectively.
      Furthermore, these differences were statistically different from both control
      therapies for all wound healing parameters (P < 0.0001). No significant increase
      in tooth root ankylosis was found among the treatment groups when compared to the
      surgery-alone group. We conclude that OP-1 offers promise as an attractive
      candidate for treating severe periodontal lesions.

PMID- 9526912
TI  - Mucogingival versus guided tissue regeneration procedures in the treatment of
      deep recession type defects.
AB  - The objective of the study was to compare the clinical efficacy of 3 surgical
      approaches in the treatment of deep recession type defects. Fifty-four (54)
      gingival recessions > or = 5 mm were randomly assigned to 1 of the 3 treatment
      groups by blocking the prognostic variables. The first group was treated with a
      guided tissue regeneration (GTR) procedure using a bioabsorbable membrane, the
      second with non-resorbable membrane, and the third with a mucogingival surgical
      approach consisting of a connective tissue graft combined with a coronally
      advanced flap (bilaminar technique). No differences, in terms of baseline oral
      hygiene and defect characteristics, were observed among the 3 groups showing an
      effective blocking approach. The 1-year results indicated that 1) all treatment
      approaches resulted in clinically significant root coverage and attachment gain;
      2) a statistically significant treatment effect (P = 0.012, ANOVA) was observed
      comparing the bioabsorbable (4.9+/-0.3 mm), the non-resorbable (4.5+/-0.8 mm),
      and the bilaminar (5.3+/-0.7 mm) groups, in terms of root coverage; 3) the
      difference in terms of root coverage between the bilaminar and the non-resorbable
      membrane groups was statistically significant while differences between the 2 GTR
      groups or between the bilaminar and the bioabsorbable membrane groups did not
      reach statistical value; 4) the 95% confidence intervals for the proportions of
      complete successes showed a similar pattern; 5) no statistical difference was
      demonstrated in the amount of attachment gain among the 3 groups (P=0.73, ANOVA).
      A regression model showed that the amount of root coverage was significantly
      affected by the initial recession depth, the procedure and smoking habits: a
      poorer root coverage result is expected in case of shallow recession type
      defects, when either bioabsorbable (P < 0.05) or non-resorbable (P < 0.001)
      membranes are used instead of a bilaminar technique and if the patient smokes (P
      < 0.01). It was concluded that the mucogingival bilaminar technique is at least
      as effective as GTR procedures in the treatment of gingival recession > or = 4 mm
      and thus recession depth is not the parameter which influences the selection of
      the surgical procedure.

PMID- 9526914
TI  - Impact of endodontic conditions on marginal bone loss.
AB  - This study was undertaken to examine the extent to which the marginal alveolar
      bone may be influenced by the condition of the dental pulp. A total of 115 pairs
      of contralateral teeth were observed in 87 patients (25 to 45 years old) in which
      the test tooth, but not the control tooth, was either endodontically treated or
      not treated but with a periapical radiolucency. The distance from the cemento
      enamel junction to the marginal bone level was measured using intraoral
      radiographs. The condition of the endodontic filling, the periapical status, and
      the presence of root canal post were also assessed. With clinical parameters
      similar between teeth in the two groups in terms of visible plaque, bleeding on
      probing, probing depth, and attachment level, the results showed a somewhat (mean
      value 0.1 mm; SD 0.7) larger reduction of the alveolar bone support in test than
      control teeth. This difference was not statistically significant on a patient
      level. Hence, this study failed to demonstrate a correlation between a reduced
      marginal bone support and endodontic status.

PMID- 9526913
TI  - Hydroxyapatite cement implant for regeneration of periodontal osseous defects in
      humans.
AB  - A newly developed calcium phosphate cement used to promote bone regeneration in
      craniofacial defects was examined to determine its potential for treatment of
      periodontal osseous defects. Sixteen patients with moderate to severe periodontal
      disease and 2 bilaterally similar vertical bony defects received initial therapy
      including scaling and root planing followed by treatment with either calcium
      phosphate cement, flap curettage (F/C) or debridement plus demineralized freeze
      dried bone allograft (DFDBA). Standardized radiographs were exposed at baseline
      and 12 months postsurgery for computer assisted densitometric image analysis
      (CADIA). The extent of the bony defect was determined during initial and 12 month
      re-entry surgery. Within 6 months of implant placement, 11 of 16 patients treated
      with calcium phosphate cement exfoliated all or most of the implant through the
      gingival sulcus. At all 16 test sites, a narrow radiolucent gap formed by 1 month
      postsurgery at the initially tight visual interface between the radiopaque
      calcium phosphate cement and the walls of the bony defect. Mean probing depth
      reduction and clinical attachment gain at sites treated with calcium phosphate
      cement were 1.6 mm and 1.3 mm, respectively at 1 year. Minimal bony defect fill
      was accompanied by mean crestal resorption of 1.4 mm. Alveolar crestal resorption
      at sites with calcium phosphate cement was statistically significant (P=0.001).
      These findings contrasted with the more favorable outcomes for controls treated
      with DFDBA or F/C. DFDBA sites exhibited probing depth reduction of 3.1 mm,
      clinical attachment gain of 2.9 mm, and defect fill of 2.4 mm. Respective
      clinical changes at F/C sites were 2.4 mm, 1.4 mm, and 1.1 mm. CADIA revealed
      clinically significant trends between the three treatment modalities at various
      areas-of-interest. Based on the findings of this study, there is no rationale
      available to support the use of hydroxyapatite cement implant in its current
      formulation for the treatment of vertical intrabony periodontal defects.

PMID- 9526915
TI  - The effect of smoking on individuals with minimal periodontal destruction.
AB  - Recent studies have demonstrated that smoking is associated with periodontal
      destruction. The majority of these studies have focused on periodontal disease
      groups with moderate or severe periodontal destruction. Additionally, there have
      been few reports investigating the relationship between smoking and gingival
      recession. The goal of this report was to investigate the effect of smoking on
      periodontal destruction and recession in subjects with minimal or no
      interproximal attachment loss. This is a cross-sectional study of 142 non-smoking
      subjects and 51 smoking subjects. Subjects could have no more than one tooth with
      a site of interproximal attachment loss > or =2 mm. Subjects could, however, have
      attachment loss associated with recession. For three different methods of
      summarizing attachment loss measurements at a subject level, including average
      attachment loss, percentage of teeth with one site of 2 mm of attachment loss,
      and the percentage of teeth with one site of 5 mm of attachment loss, smoking
      subjects had approximately twice as much attachment loss than their non-smoking
      counterparts. Smoking subjects also had significantly greater recession (P <
      0.05) [0.056+/-0.017 mm] than non-smoking subjects (0.025+/-0.005 mm). Recession
      sites occurred primarily on the facial surface of maxillary molars and bicuspids
      and mandibular central incisors and bicuspids. The results suggest a strong
      association between smoking and both attachment loss and recession in subjects
      who have minimal or no periodontal disease.

PMID- 9526916
TI  - The influence of smoking and race on adult periodontitis and serum IgG2 levels.
AB  - Smoking is a known risk factor for developing periodontal diseases, but the risk
      appears to be greater for white smokers than black smokers. Furthermore, it has
      been reported that young white subjects have significantly lower levels of serum
      IgG2 than their non-smoking counterparts while young black adult subjects are
      generally not affected by smoking. These relationships prompted the hypothesis
      that adult white subjects, including periodontitis subjects, who smoked would
      have more attachment loss than adult black subjects and that smoking would be
      associated with lower serum IgG2 levels in adult white subjects but not in adult
      black subjects. Smoking status was established from serum cotinine levels
      determined by radioimmunoassay. Serum IgG subclass levels were determined using
      radial immunodiffusion. White adult periodontitis (AP) and non-periodontitis (NP)
      subjects who smoked had greater mean attachment loss per site than their non
      smoking counterparts. Furthermore, smoking white AP subjects and their age
      matched NP controls had substantially less IgG2 in their serum. In marked
      contrast, we were unable to detect any increase in periodontal destruction or a
      significant decrease in serum IgG2 levels in smoking black AP subjects or their
      age-matched controls. However, IgG1 and IgG4 levels were reduced in smoking black
      AP subjects. IgG3 was the only subclass in adults that was unaffected by smoking.
      IgG2 can be a good opsonin and may help control periodontitis-associated bacteria
      in adults. Even though a cause-and-effect relationship has not been established,
      the association between a smoking-related decrease in serum IgG2 and an increase
      in periodontal destruction in white subjects is striking.

PMID- 9526917
TI  - Histologic observations on 230 retrieved dental implants: 8 years' experience
      (1989-1996).
AB  - The histologic examination of dental implants retrieved from humans is important
      to establish the causal determinants of implant failure, and to compare and
      validate the results obtained from animal studies. This study presents a
      retrospective review of the histologic features of 230 implants retrieved in an 8
      year period (1989-1996). All the implants were treated to obtain thin (20 to 30
      microm) ground sections. The majority of implants were retrieved because of
      mobility (n=56), peri-implantitis (n=54), or fractures (n=90). Peri-implantitis
      occurred more frequently before (n=44) than after (n=10) abutment connection. A
      dense fibrous connective tissue with no inflammatory cells was present at the
      interface in the implants retrieved for mobility; bone was found only in the most
      apical part. In many of these implants epithelial cells were present. The main
      histologic features of peri-implantitis consisted of the presence of a bone
      sequestrum near the implant, many bacteria present on the implant surface, and an
      inflammatory infiltrate (macrophages, lymphocytes, and plasma-cells) nearby.
      Histology showed that in the implants removed for fracture, there was a very high
      percentage (80 to 100%) of peri-implant bone.

PMID- 9526918
TI  - Hollow implants retrieved for fracture: a light and scanning electron microscope
      analysis of 4 cases.
AB  - One of the possible complications of implant treatment is the occurrence of an
      implant fracture. Metal fatigue and biomechanical overload seem to be the most
      common causes of fractured implants. This study evaluated 4 implants (3 hollow
      cylinders and 1 hollow screw) which fractured after a mean loading period of 2.8
      years. All implants had a 4 mm diameter and had been inserted in a posterior
      location. In 3 cases parafunctional habits were present. In all cases a vertical
      resorption of the peri-implant bone was present. The endosseous portion of the
      implant presented always a very high bone-implant contact percentage. Scanning
      electron microscopic examination showed that at least one of the implant holes
      was involved in the fracture line; no porosities or material defects were
      observed on the fractured surface of the implant. In hollow implants the holes
      could represent a site of less resistance.

PMID- 9526920
TI  - Histopathological investigation of gingival tissue from patients with rapidly
      progressive periodontitis.
AB  - In this study, fine structural features of the pocket walls in rapidly
      progressive periodontitis (RPP) and adult periodontitis (AP) in 20 cases were
      compared using light and transmission electron microscopy. Gingiva was also
      obtained from a control group of periodontally healthy teeth. Clinical parameters
      were assessed in both RPP and AP patients and in controls. Bone destruction and
      attachment loss were more marked in RPP than in AP. Light microscopical
      observations of inflamed RPP tissue as compared to AP showed gross histological
      distortions in the pocket walls. Micro-ridges within the epithelium and large
      intercellular spaces between the epithelial cells were observed in most RPP
      biopsies. Epithelial cells surrounding the microclefts and adjacent keratinocytes
      were found to produce interleukin-1beta (IL-1beta). Prevotella intermedia and
      Porphyromonas gingivalis were identified in the RPP biopsies using
      immunohistological methods. These microorganisms were localized outside the
      epithelium and inside intercellular spaces. Furthermore, the effect of
      inflammation on the distribution of collagen types I, III, IV, V, and VI in the
      human gingiva was studied after staining them with antibodies to these proteins.
      In RPP and AP tissues, the staining was sparse in areas of inflammation and
      leukocytic infiltration. Collagen type I and III were almost entirely lost at
      sites of inflammation. Type V and VI collagen antibodies were retained in
      inflamed areas. Type IV collagen was restricted to basement membrane structures.
      These observations demonstrated numerous structural features indicative of more
      pronounced degenerative changes in RPP than in AP.

PMID- 9526919
TI  - Microbiota associated with experimental peri-implantitis and periodontitis in
      adult Macaca mulatta monkeys.
AB  - This study examines the microbiota associated with the progression of
      experimental peri-implantitis and periodontitis induced concurrently in partially
      edentulous adult monkeys. Root-form and plate-form implants with fixed prosthesis
      in place for at least 12 months and their corresponding opposite molar teeth were
      ligated for 6 months. The microbiota in plaque around these ligated dental
      implants and molars were studied at 0, 1, 2, 3, and 6 months post-ligation.
      Plaque samples were analyzed by dark-field microscopy and selective and non
      selective culture. Putative periodontal pathogens were detected as a major
      component of the microbiota cultured from plaque samples obtained from
      experimental peri-implantitis sites. Overall, the types and relative proportions
      of putative periodontal pathogens in plaque associated with ligature-induced peri
      implantitis and ligature-induced periodontitis were similar. Only levels of
      anaerobic Actinomyces and spirochetes were significantly different between both
      sites. Spirochete levels were significantly higher at peri-implantitis sites when
      compared with levels at periodontitis sites after 6 months, and spirochete levels
      increased significantly between 0 and 6 months post-ligation at implant sites.
      Levels of spirochetes correlated significantly with probing depth and bone loss
      at peri-implantitis sites. Overall, Actinomyces levels were higher at
      periodontitis sites. Porphyromonas species were not detected continuously as part
      of the peri-implantitis microbiota. In conclusion, this study finds that the
      microbiota associated with the progression of experimental peri-implantitis and
      periodontitis occurring concurrently in partially edentulous mouths are similar.

PMID- 9526921
TI  - Cytoskeletal actin reorganization in neutrophils from patients with localized
      juvenile periodontitis.
AB  - Localized juvenile periodontitis (LJP) is an early-onset periodontal disease
      associated with a polymorphonuclear neutrophil (PMN) defective migratory
      response. Kinetics of actin polymerization-depolymerization determine the shape
      changes occurring in the plasma membrane-associated cytoskeleton and provide the
      driving force for directed cell migration (chemotaxis). Therefore, we
      investigated the relation between an abnormality in LJP PMN chemotaxis and an
      altered reorganization of the actin filament network. PMNs isolated from
      peripheral blood of LJP patients (n=14) and matching control subjects (n=12) were
      evaluated for random and directed migration in a Boyden chamber assay, and the
      kinetics of actin polymerization were studied by flow cytometry. Three groups of
      LJP patients could be distinguished on the basis of their PMN-chemotactic
      response compared to their matched control: depressed (n=6), normal (n=4), and
      elevated (n=4). The abnormal (depressed or elevated) chemotaxis was generally not
      related to abnormal random migratory response, except for two patients. Since the
      kinetics of formyl-methionyl-leucyl-phenylalanine-induced F-actin response were
      highly variable from one subject to another, means were calculated at each
      timepoint with the values obtained from each group of subjects and compared by a
      general factorial design analysis. No statistically significant differences were
      detected between the control group and the LJP patient group. Furthermore, the
      data did not show a correlation between the kinetics of actin polymerization
      depolymerization and the abnormal chemotactic response observed in LJP PMNs.
      Hence, the chemotaxis defect in LJP PMN appears to be mediated by signaling
      events that carry their effect independently of an intact cytoskeleton.

PMID- 9526923
TI  - Concepts of quality and the provision of periodontal care: a survey.
AB  - This is a survey of various concepts of quality of care in the health care field
      and their application to periodontics. Definitions of quality care, measuring and
      improving quality, third party payment and quality of care, and the role of
      periodontists in managing quality are presented. The definitions of quality care
      include the following dimensions: access, appropriateness, technical quality, and
      the art of care. Examples of each of these dimensions are presented, and their
      implications for quality assessment are discussed. Emphasis is placed on
      appropriateness of care and the strengths and weaknesses of mechanisms for
      deriving evidence-based decision making. The use of randomized clinical trials
      (RCT), employing expert opinion such as consensus panels, and meta-analysis are
      discussed as they apply to appropriateness of periodontal treatment. Work in the
      area of technical quality of care (i.e., the third dimension of quality care) has
      resulted in the development of quality assurance guidelines. Examples of
      guidelines and practice parameters such as those developed by the U.S. Food and
      Drug Administration and by various dental specialties are presented. The fourth
      dimension of quality deals with the art of care. It focuses on the patient's
      participation in the process of care and the input of the provider in this
      interaction. The description of outcomes of care includes the concept of
      measuring clinical outcomes of treatment as well as efforts to measure the health
      and well-being of a patient. It deals with quality of life measures. Patient
      satisfaction is another outcome that is presented. Examples of these aspects of
      quality measurement are discussed. These concepts and measures are presented
      within the context of a quality assurance program. The steps used to assess and
      assure quality are outlined. Examples of provider and patient profiles are
      presented, along with a discussion on how they are used in a quality assurance
      system. Lastly, the role of the periodontist in quality of care is presented,
      emphasizing the efforts that have already been made as well as the leadership
      role that the periodontist has in influencing the profession of dentistry. The
      advent of managed care and its implications for the quality of periodontal
      treatment and patient management are discussed using situations obtained from
      dental plans.

PMID- 9526922
TI  - Inflammatory cervical root resorption following segmental orthognathic surgery. A
      case report.
AB  - An unusual case of bilateral inflammatory external/internal root resorption
      developed in the maxillae of a 28 year-old female approximately 4 years following
      routine segmental orthognathic surgery. The patient experienced dental pain in a
      tooth adjacent to a segmental osteotomy cut 8 months postsurgery, however, the
      tooth later became asymptomatic. A definitive diagnosis of inflammatory cervical
      root resorption was not established until nearly 4 years later on routine dental
      examination. The external/internal resorptive lesions were located 4 to 6 mm
      apical to the connective tissue attachment on 3 of the 4 tooth roots adjacent to
      osteotomy cuts. Two of the affected teeth required non-surgical root canal
      therapy due to pulpal communication with the resorptive defects. The lesions were
      accessed by flap surgery, thoroughly debrided, and obturated with an intermediate
      restorative material until definitive restorative therapy could be completed. All
      sites healed uneventfully and the patient has been closely observed for
      approximately 2 years without symptoms or recurrence of the resorptive lesions.
      Dental health care providers should be alert to the possible occurrence of
      inflammatory root resorption in sites adjacent to osteotomy cuts over extended
      periods of time. Routine radiographic examination may be beneficial in the
      postoperative management of the segmental orthognathic surgery patient.

PMID- 9526924
TI  - Economic models to help periodontists evaluate their practices: how to analyze a
      practice to assess the potential impact of managed care contracts.
AB  - The purpose of this article is to examine 10 steps analyzing the financial impact
      on a periodontal practice accepting a proposed managed care dental plan. It is
      emphasized that this analysis should be conducted before formally agreeing to
      accept the proposed plan. The procedures for examining the 10 steps include the
      use of hypothetical data for a periodontal practice confronted with a discounted
      fee plan. Each step is identified, discussed, and the hypothetical data are used
      to develop results presented in a set of tables. The steps in the analysis
      process include constructing a practice profit and loss statement and developing
      a dataset of practice characteristics and productivity measures. Other estimates
      should be made of covered lives, new patient utilization, existing patient
      utilization, utilization of non-covered services, estimating other sources of
      revenue and expense, and the impact on capacity utilization of operatories and
      practice staff. Results are presented in a set of analysis tables. The importance
      of multiple analyses is discussed as is the importance of analyzing the impact on
      results from changing assumptions. Some of the higher risk variables faced by the
      practitioner are identified for submission to risk evaluation to examine the
      sensitivity of results. Finally, the relationship between the proposed plan and
      the additional time required by the periodontist to meet the plan's
      specifications is examined in light of the data developed in the 10 steps and the
      results tables.

PMID- 9526925
TI  - Legal considerations for periodontists in dealing with managed care
      organizations.
AB  - For well over a decade, increasing numbers of medical patients have transferred
      from traditional indemnity insurance to managed care organizations (MCOs).
      Increasingly, MCOs are enrolling dental patients as well. Consequently, it is
      important for periodontists to understand issues in negotiating with MCOs. This
      article attempts to advise periodontists regarding what they can and cannot do
      collectively about managed care and what considerations they should take into
      account in individually negotiating and dealing with managed care plans.

PMID- 9526926
TI  - Dental insurance and the periodontal patient.
AB  - Approximately one-half of the United States population is covered by a dental
      benefit plan. One-fifth of that group is covered under various types of managed
      care contracts, and this number is said to be increasing by 15% to 20% per year.
      However, dentists report that these plans have not had a major impact upon their
      practices. Only 6% of patients were covered by them, and only 2% of gross
      receipts were derived from them. Periodontists surveyed were divided in their
      opinions about how managed care has affected their practices. This paper
      discusses these changes, particularly with regard to income, referral patterns,
      treatment decisions, and ethical and legal liability.

PMID- 9526927
TI  - Periodontal diseases in the United States population.
AB  - Recent epidemiologic surveys and studies have provided important information on
      the prevalence, extent, and severity of periodontal diseases in the United
      States. Over 50% of adults had gingivitis on an average of 3 to 4 teeth.
      Subgingival calculus was present in 67% of the population. Adult periodontitis,
      measured by the presence of periodontal pockets > or = 4 mm, was found in about
      30% of the population on an average of 3 to 4 teeth. Severe pockets > or = 6 mm
      were found in less than 5% of the population. Attachment loss > or = 3 mm was
      found in 40% of the population. Gingival recession accounted for a significant
      amount of attachment loss. The prevalence of early-onset periodontitis ranged
      from less than 1% in 14- to 17-year-olds to 3.6% in young adults aged 18 to 34.
      Extensive and severe periodontitis was much more prevalent in minorities, people
      with less than a high school education, and those who had seen a dentist
      infrequently and had subgingival calculus. Smoking and diabetes have been
      identified as risk factors, especially diabetics with poor metabolic control, a
      long duration of the disease, and extensive subgingival calculus. Under managed
      care, there has been an expansion of soft tissue management programs in the
      offices of general dentists and referral guidelines which limit referral of
      patients with moderate periodontitis. Quality-assurance mechanisms will be
      essential for the diagnosis and treatment of persons with periodontitis.

PMID- 9526928
TI  - Report of the American Academy of Periodontology's Workshop on the Design and
      Conduct of Clinical Trials for Endosseous Dental Implants.

PMID- 9526929
TI  - Cross-sectional area and intravascular pressure of the right internal jugular
      vein during anesthesia: effects of Trendelenburg position, positive intrathoracic
      pressure, and hepatic compression.
AB  - STUDY OBJECTIVE: To determine changes in the cross-sectional area of the right
      internal jugular vein (RIJV) in response to positive intrathoracic pressure and
      hepatic compression in mechanically ventilated patients during general
      anesthesia. DESIGN: Prospective, nonrandomized study. SETTING: A university
      medical center. PATIENTS: 15 ASA physical status II and III adult patients
      undergoing RIJV cannulation after anesthetic induction and endotracheal
      intubation. INTERVENTIONS: Patients were studied first supine and then at a 10
      degrees and 20 degrees Trendelenburg tilt. The cross-sectional area of the RIJV
      was determined by two-dimensional ultrasound before and during 1) an end
      inspiratory hold of 20 cm H2O; 2) hepatic compression for 10 seconds; and 3) both
      maneuvers applied simultaneously. Subsequently, the RIJV was cannulated and the
      intravascular pressure was measured during the same sequence of maneuvers.
      MEASUREMENTS AND MAIN RESULTS: In supine patients, the cross-sectional area of
      the RIJV significantly increased during the end-inspiratory hold, during hepatic
      compression, and with both maneuvers performed simultaneously (p < 0.05). With a
      10 degrees Trendelenburg tilt, only both maneuvers applied simultaneously
      increased the cross-sectional area of the RIJV significantly, and with the 20
      degrees Trendelenburg tilt, no further increase was seen. Intravascular pressure
      of the RIJV consistently increased with each maneuver in all positions.
      CONCLUSION: Hepatic compression and positive inspiratory hold effectively dilate
      the RIJV in supine patients and can be used when the Trendelenburg position is
      not advisable or possible. Performing these maneuvers with patients in the
      Trendelenburg position may facilitate cannulation, possibly by making the vein
      less collapsible due to increased intravascular pressure.

PMID- 9526930
TI  - Droperidol-ondansetron combination versus droperidol alone for postoperative
      control of emesis after total abdominal hysterectomy.
AB  - STUDY OBJECTIVES: To investigate the hypothesis that the combination of
      ondansetron and droperidol would be more effective than droperidol alone in
      reducing nausea and vomiting. DESIGN: Randomized, doubleblind study. SETTING:
      Magee-Womens Hospital, Pittsburgh, Pennsylvania. PATIENTS: 160 healthy, ASA
      physical status I and II, female patients scheduled for total abdominal
      hysterectomy. INTERVENTIONS: After induction of anesthesia with propofol, Group 1
      received intravenous (i.v.) droperidol 1.25 mg plus i.v. ondansetron 4 mg. Group
      2 received i.v. droperidol plus i.v. saline. MEASUREMENTS AND MAIN RESULTS: The
      complete response (no emesis, no rescue) for Group 1 was 36 of 80 patients (45%)
      versus 30 of 80 patients (38%) in Group 2 (p = 0.21). In Group 1, 42 of 80
      patients (53%) required rescue antiemetic as compared with 44 of 80 patients
      (55%) in Group 2 (p = 0.43). There were 72 total rescues in Group 1 versus 73 in
      Group 2, (p = 0.24). Mean time until first rescue was 578 +/- 429 minutes in
      Group 1 and 418 +/- 354 minutes in Group 2, (p = 0.03). In Group 1, 81 % (34/42)
      were rescued for nausea only versus 90% (39/44) of Group 2 (p = 0.16). In Group
      1, 21% of patients (17/80) had at least one emetic episode versus 34% (27/80) of
      Group 2 patients (p = 0.05). There were 31 emetic episodes in Group 1 versus 72
      episodes in Group 2. (p = 0.02). Mean time to the first emetic episode was 699 +/
      403 minutes in Group 1 and 616 +/- 376 minutes in Group 2, (p = 0.23).
      CONCLUSION: For patients undergoing total abdominal hysterectomies, the addition
      of ondansetron to droperidol increases the time until first rescue and reduces
      the number of emetic episodes, as well as the percentage of patients, having at
      least one emetic episode.

PMID- 9526931
TI  - Effects of oral diazepam on intravenous access in same day surgery patients.
AB  - STUDY OBJECTIVE: To determine the effects of 5 mg oral diazepam on vein quality,
      patient anxiety, and intravenous (i.v.) access. DESIGN: Prospective, randomized,
      double-blind, placebo controlled study. SETTING: Preoperative holding area of a
      large university hospital. PATIENTS: 202 adult ASA physical status I, II, and III
      patients scheduled for elective outpatient surgery. INTERVENTIONS: Patients were
      randomized to receive either 5 mg oral diazepam or placebo, 30 minutes prior to
      i.v. access. MEASUREMENTS AND MAIN RESULTS: Vein quality and patient anxiety were
      assessed prior to, and 30 minutes following, premedication (just prior to
      venipuncture) using a 5 point ordinal scale and 10 cm visual analog scale,
      respectively. The number of attempts at venous access and the gauge of the
      catheter used were also recorded. Baseline patient anxiety was similar between
      the two groups and both showed a significant improvement in patient anxiety at 30
      minutes following drug administration. The diazepam group, however, had a
      significantly greater reduction in anxiety scores (p < 0.05). There were no
      differences in baseline vein quality between the two groups; however, the quality
      of the vein was subjectively improved following diazepam administration. The mean
      number of attempts at i.v. access between the diazepam group (1.26 +/- 0.56) and
      the placebo group (1.32 +/- 0.65) was not significantly different. However, the
      ability to place larger gauge catheters was significantly enhanced in the
      diazepam group. CONCLUSIONS: The administration of 5 mg oral diazepam prior to
      the establishment of i.v. access improved vein quality and decreased patient
      anxiety. This technique may be a useful method for i.v. catheter placement,
      particularly when large gauge catheters are required, or when difficult i.v.
      access is anticipated.

PMID- 9526932
TI  - Changes in body temperature following deflation of limb pneumatic tourniquet.
AB  - STUDY OBJECTIVES: To investigate changes in both core and peripheral skin-surface
      temperatures during and after application of a unilateral leg pneumatic
      tourniquet in adult patients. DESIGN: Prospective, observational clinical study.
      SETTING: University hospital. PATIENTS: 21 ASA physical status I and II adult
      patients scheduled for elective leg orthopedic surgery with lumbar epidural
      anesthesia. INTERVENTIONS: Rectal and fingertip skin-surface temperatures were
      recorded every minute after steady-state lumbar epidural anesthesia was
      established. MEASUREMENTS AND MAIN RESULTS: Significant (p < 0.05) increases in
      both rectal and fingertip temperatures were observed during tourniquet
      application for 91 +/- 6 minutes from 36.5 +/- 0.14 degrees C to 37.0 +/- 0.17
      degrees C and from 32.6 +/- 0.79 degrees C to 35.5 +/- 0.44 degrees C,
      respectively. In contrast, both rectal and fingertip temperatures progressively
      decreased following tourniquet release; significant (p < 0.05) decreases in the
      rectal and fingertip temperatures were observed 6 and 5 minutes after tourniquet
      release, respectively. Decreases (approximately maximum) in the rectal and
      fingertip temperatures 15 minutes after tourniquet release were 0.25 +/- 0.05
      degrees C and 1.26 +/- 0.26 degrees C, respectively. In each case, changes in
      fingertip temperature were approximately six times greater than those in the
      rectal temperature. CONCLUSIONS: Limb tourniquets appear to cause thermal
      perturbations during epidural anesthesia. The progressive increases in core
      temperature during tourniquet application presumably resulted from constraint of
      metabolic heat to the core thermal compartment, and the greater increases in the
      skin-surface temperature during tourniquet application appear to represent
      vasodilation in response to the core hyperthermia. On the other hand,
      redistribution of body heat and the efflux of hypothermic venous blood from the
      tourniqueted area into systemic circulation following tourniquet deflation
      probably decreased the core temperature, which might switch off the
      thermoregulatory vasodilation, leading to the decreases in skin-surface
      temperature. Recognition of these thermal perturbations are useful in diagnosing
      intraoperative thermal perturbations.

PMID- 9526933
TI  - Comparative effects of Ringer's acetate and lactate solutions on intraoperative
      central and peripheral temperatures.
AB  - STUDY OBJECTIVES: To compare the effects of Ringer's lactate (LR) and Ringer's
      acetate (AR) solutions on core body and peripheral temperatures during isoflurane
      or sevoflurane anesthesia. DESIGN: Prospective, randomized study. SETTING:
      Operating rooms of a university hospital. PATIENTS: 60 ASA physical status I and
      II patients undergoing general surgery. INTERVENTIONS: Following induction with 5
      mg/kg of thiamylal and 0.1 mg/kg of vecuronium, patients were randomly assigned
      to one of four groups (15 patients per group). They received inhalation
      anesthetics (66% nitrous oxide [N2O] and 1.0% to 2.0% isoflurane or 1.3% to 2.6%
      sevoflurane) and LR or AR. MEASUREMENTS AND MAIN RESULTS: Tympanic membrane
      (central) temperatures, forearm temperatures, and fingertip temperatures were
      recorded during surgery every 30 minutes. Tympanic membrane temperatures in the
      patients given AR were significantly higher than those given LR during isoflurane
      anesthesia 5 and 30 minutes after induction of anesthesia. However, this was not
      the case for sevoflurane anesthesia. There were no significant differences in
      forearm and fingertip temperatures or fingertip bloodflow among the four groups.
      CONCLUSION: There was no significant difference between AR and LR in the
      preservation of heat during either sevoflurane or isoflurane anesthesia. However,
      AR may be superior to LR for maintaining central temperature during the early
      period of isoflurane anesthesia.

PMID- 9526934
TI  - Improving the efficiency of survey research in postoperative patients.
AB  - STUDY OBJECTIVE: To increase the contact rate with eligible patients for quality
      assurance/improvement surveys by modifying survey rounds to accommodate the
      schedules of individual nursing units. DESIGN: Two-phase, interventional time
      series study. SETTING: Postoperative inpatients at a university hospital.
      PATIENTS: 498 adult postoperative inpatients who remained hospitalized during the
      second postoperative day. INTERVENTIONS: Between the first and second measurement
      periods, efforts were made to learn the schedule of each nursing unit and to
      improve the efficiency of survey rounds so that a larger proportion of patients
      could be contacted. MEASUREMENTS AND MAIN RESULTS: The contact rate for eligible
      patients was improved from 66% to 80% (p < 0.01). Improvement during the second
      period was attributed to fewer patients being away from the nursing unit (20% vs.
      12%, p < 0.05) or otherwise occupied by attending physicians on rounds (9% vs.
      4%, p < 0.05). CONCLUSION: Strategies individualized to patient care units can
      improve the efficiency and credibility of inpatient survey research. We describe
      the strategies most helpful in improving the efficiency of survey rounds at one
      medical center.

PMID- 9526935
TI  - Hemodynamic evaluation of the prone position by transesophageal echocardiography.
AB  - STUDY OBJECTIVE: To evaluate the hemodynamic response in the prone position in
      surgical patients by measuring the effects of prone positioning on cardiac
      function using transesophageal echocardiography (TEE). DESIGN: Prospective study.
      SETTING: Elective surgery at a university hospital. PATIENTS: 15 adult ASA
      physical status I and II patients free of significant coexisting disease
      undergoing lumbar laminectomy. INTERVENTIONS AND MEASUREMENTS: Approximately 15
      minutes after the induction of general anesthesia, we measured heart rate, blood
      pressure, and central venous pressure. We also measured left ventricular area
      (LVA) and fractional area change (FAC) automatically and calculated left
      ventricular volume (LVV), stroke volume index (SVI), cardiac index (CI), left
      ventricular ejection fraction (LVEF), left ventricular fractional shortening
      (LVFS), pulmonary venous flow velocity (PVFV), and pulmonary venous velocity time
      integral (PVVTI) via TEE. The same measurements were performed approximately 15
      minutes after changing to the prone position with longitudinal bolsters. MAIN
      RESULTS: In the prone position, there was significant reduction in end-systolic
      and end-diastolic LVA and LVV. There was a significant increase in LVEF, LVFS,
      and FAC in the prone position. In addition, there was diminishment of systolic
      PVFV and PVVTI and enhancement of diastolic PVFV and PVVTI. SVI and CI did not
      change significantly in the prone position. CONCLUSION: The prone position caused
      LVV to decrease. The prone position also led to decreased systolic PVFV and PVVTI
      and enhancement of diastolic PVFV and PVVTI. These changes were probably due to a
      decrease in the venous return due to inferior vena caval compression, and
      decreased left ventricular compliance due to increased intrathoracic pressure in
      the prone position.

PMID- 9526936
TI  - Pharmacy savings generated by preoperative administration of clonidine.
AB  - STUDY OBJECTIVE: To evaluate the effects of the preoperative administration of
      clonidine by the oral, intramuscular (i.m.), or epidural routes, on isoflurane
      expense during total abdominal hysterectomy. DESIGN: Randomized, double-blind,
      placebo-controlled study. SETTING: University hospital. PATIENTS: 80 ASA physical
      status I and II patients scheduled for total abdominal hysterectomy.
      INTERVENTIONS: Patients were distributed into four groups of treatment: oral,
      i.m., epidural, and control. Each group received 300 microg clonidine according
      to the treatment group, plus placebo by the other routes. The control group
      received placebo by all three routes. Depth of anesthesia was evaluated by
      changes in blood pressure and heart rate over baseline values. Cost evaluation
      was based on three components: expense of isoflurane, cost of 300 microg of
      clonidine (tablets or ampoules), and the disposable material required to dispense
      clonidine to each group. MEASUREMENTS AND MAIN RESULTS: Groups were comparable
      regarding demographic data, duration of surgery, and time to discharge from
      recovery room. Postoperatively, none of the patients had recall of intraoperative
      events. Clonidine reduced isoflurane pharmacy cost by approximately 45%,
      regardless of the route of administration. However, when cost of clonidine and
      the disposable equipment used for its administration were taken into account, the
      cost of the epidural kit surmounted the savings in isoflurane expense.
      CONCLUSION: In the patient population studied, premedication with 300 microg
      oral, i.m., or epidural clonidine, similarly and significantly reduced the
      expense of isoflurane during general anesthesia of an approximate duration of two
      hours. However, the cost of the epidural kit offsets the savings in isoflurane.

PMID- 9526937
TI  - High concentration versus incremental induction of anesthesia with sevoflurane in
      children: a comparison of induction times, vital signs, and complications.
AB  - STUDY OBJECTIVE: To compare sevoflurane induction times and complications in
      children during a high concentration, primed-circuit method and an incremental
      induction technique. DESIGN: Randomized, prospective open-label study. SETTING:
      Academic university hospital. PATIENTS: 40 unpremedicated ASA physical status I
      and II children age 4 months to 15 years undergoing elective surgical procedures
      with general anesthesia. INTERVENTIONS: Patients were randomized to one of two
      study groups. In the high concentration group, the anesthesia circuit was primed
      with 8% sevoflurane in a 2:1 nitrous oxide:oxygen (N2O:O2) mixture. Patients
      breathed this gas mixture spontaneously until loss of the eyelash reflex. In the
      incremental group, the face mask was applied and 1% sevoflurane in a 2:1 N2O:O2
      mixture was administered. In this group, the sevoflurane concentration was
      increased by 1% every 2 to 3 breaths. Gas flows of 6 L/min were administered to
      both groups during the study period. Following loss of the eyelash reflex, the
      sevoflurane concentration was decreased to 5% until a depth of anesthesia
      sufficient to start an intravenous catheter was achieved. MEASUREMENTS AND MAIN
      RESULTS: Induction cooperation, induction time (face mask application to loss of
      the eyelash reflex), one-minute vital signs [blood pressure, heart rate, oxygen
      saturation via pulse oximetry (SpO2)], induction complications. Induction of
      anesthesia was faster in the high concentration group than in the incremental
      group (mean (SD) 42 (9) sec vs. 66 (12) sec, respectively; p < 0.001). Induction
      complications were minor and occurred with similar frequencies (4/20 patients vs.
      3/20 patients). There were no significant intergroup heart rate, blood pressure,
      or SpO2 differences during induction. No patients required treatment for
      hypotension or bradycardia. CONCLUSIONS: In healthy pediatric patients undergoing
      mask induction of general anesthesia with sevoflurane, the induction time can be
      significantly shortened without an increase in the frequency of airway or vital
      sign complications using a high concentration, primed circuit technique compared
      with a conventional, incremental induction method.

PMID- 9526938
TI  - Remifentanil versus propofol as adjuncts to regional anesthesia. Remifentanil
      3010 Study Group.
AB  - STUDY OBJECTIVE: To compare the safety and efficacy of remifentanil and propofol
      as adjuncts to regional anesthesia in patients undergoing orthopedic or
      urogenital surgery. DESIGN: Prospective, randomized study. SETTING: Multicenter
      university hospitals. PATIENTS: 107 ASA physical status I, II, and III adult
      patients who underwent orthopedic or urogenital surgery with axillary, ankle, or
      spinal block. INTERVENTIONS: Patients were randomized to receive either an
      infusion of remifentanil 0.2 microg/kg/min or propofol 100 microg/kg/min 5
      minutes before nerve block placement. The infusions were decreased by 50% on
      block completion, increased by 50% for patient discomfort, and decreased by 50%
      for hypoventilation (< 8 breaths/min) or hemodynamic instability. MEASUREMENTS
      AND MAIN RESULTS: Pain, discomfort, anxiety, and sedation were assessed by both
      patient and investigator. Vital signs and adverse events were recorded. Fewer
      patients in the remifentanil group experienced pain during block placement (6%),
      and were oversedated (7%) than patients in the propofol group (23% and 26%,
      respectively; p < 0.05). Hypoventilation during and after block placement (21%
      and 25%, respectively) and nausea and vomiting during and after block placement
      (60% and 21%, respectively) were more common in the remifentanil group than in
      the propofol group (0% and 3%; 17% and 6%, respectively; p < 0.05). The incidence
      of hypoventilation in remifentanil-treated patients was higher in patients over
      65 years of age (p < 0.05), but was transient, resolving within minutes of
      discontinuing the infusion. CONCLUSIONS: At the doses studied, remifentanil was
      more effective than propofol in minimizing pain without producing excessive
      sedation. Remifentanil was associated with more transient respiratory depression
      and short-term nausea. Our findings indicate that the initial remifentanil rate
      should be 0.1 microg/kg/min (50% lower than the study's initial rate) and should
      be further decreased an additional 50% in the elderly to minimize adverse
      effects.

PMID- 9526939
TI  - Cardiovascular stability during carotid endarterectomy: endotracheal intubation
      versus laryngeal mask airway.
AB  - STUDY OBJECTIVE: To compare cardiovascular stability during carotid
      endarterectomy in groups managed either with laryngeal mask airway (LMA) or
      endotracheal intubation. DESIGN: Randomized, retrospective, blinded study.
      SETTING: Teaching hospital. PATIENTS: 61 ASA physical status II, III, and IV
      unpremedicated adult males scheduled for carotid endarterectomy. INTERVENTIONS:
      Following standardized anesthetic technique, including intravenous (i.v.)
      induction with thiopental sodium 3 to 4 mg/kg, fentanyl 2 to 3 microg/kg), and
      isoflurane, standard intraoperative cardiovascular monitoring plus direct
      arterial blood pressure measurements were instituted. Patients were randomly
      assigned to an endotracheal intubation or LMA group. MEASUREMENTS AND MAIN
      RESULTS: Distinct intraoperative episodes of +/- 25% increase or decrease of mean
      arterial blood pressure (MABP) and heart rate (HR) when compared with
      preinduction baseline values, and the number of such episodes requiring
      interventional therapy were recorded from a blinded anesthesia record
      retrospectively. Mean end-tidal isoflurane determination and total case duration
      enabled calculation of minimum alveolar concentration (MAC) hours of isoflurane
      administered. The LMA group had a significantly (p < 0.05) lower incidence of
      increased MABP and HR episodes and such episodes requiring drug therapy than did
      the endotracheal intubation group. No difference was found in the length of
      surgery, mean end-tidal isoflurane concentration, or the total number of MAC
      hours of isoflurane administered. CONCLUSIONS: During carotid endarterectomy, a
      reduced incidence of hypertensive and tachycardic episodes, as well as such
      episodes requiring interventional drug therapy, was found in the group whose
      airway is managed by LMA when compared with endotracheal intubation.

PMID- 9526940
TI  - Does epidural analgesia cause dystocia?
AB  - STUDY OBJECTIVE: To analyze the effects of epidural analgesia for labor when
      dystocia occurs. DESIGN: Retrospective cohort study. SETTING: Academic health
      center. PATIENTS: 641 low risk, nulliparous women in spontaneous labor.
      INTERVENTIONS: 406 (63%) women received epidurals analgesia and 253 (37%) did
      not. Sixty women (9.4%) required an abdominal delivery for dystocia. MEASUREMENTS
      AND MAIN RESULTS: Women receiving epidural analgesia were more likely to be
      white, receive care from an attending physician, need labor augmentation, and
      deliver a heavier infant. Multivariate analysis identified five variables
      predictive of dystocia and abdominal delivery: pitocin augmentation odds ratio
      (O.R.) = 3.9 (2.0 to 7.6), duration of labor more than 20 hours O.R. = 2.4 (1.3
      to 4.4), high epidural dose O.R. = 2.2 (1.2 to 4.1), birthweight over 4,000 grams
      O.R. = 2.0 (1.0 to 4.2), and early placement of epidural O.R. = 1. 9 (1.0 to
      3.5). Repeating the regression after excluding the 20 women who developed
      abnormal labor prior to epidural placement (18 of 20 women had protracted
      dilatation) demonstrated that pitocin augmentation O.R. = 4.0 (1.8 to 4.), high
      epidural dose O.R. = 3.0 (1.9 to 6.2), duration of labor greater than 20 hours
      O.R. = 2.7 (1.3 to 5.7), and birthweight over 4,000 grams O.R. = 2.1 (0. 9 to
      4.8) were associated with dystocia. CONCLUSION: Epidural analgesia appears to be
      a marker of abnormal labor rather than a cause of dystocia. High concentration
      anesthetics and epinephrine should be avoided, as they may influence labor.
      Randomized, controlled trials of this technique will be difficult to do; our work
      should reassure patients and their clinicians that epidural analgesia does not
      adversely affect labor.

PMID- 9526941
TI  - Cauda equina syndrome after incidental total spinal anesthesia with 2% lidocaine.
AB  - A 77 year-old male presented for a right popliteal distal vein bypass graft
      procedure with continuous epidural anesthesia and light general endotracheal
      anesthesia. After the uneventful placement of the epidural needle and catheter at
      the L2-L3 interspace, fentanyl 150 microg and a total of 72 ml of preservative
      free 2% lidocaine with epinephrine was continually injected through the epidural
      catheter for the duration of the more than 5 hour procedure. At the end of the
      procedure, it was noted that the patient had developed total spinal anesthesia,
      and his pupils were fixed and dilated. Further examination confirmed that the
      catheter tip was placed in the subarachnoid space. The patient was unable to turn
      or sit up by himself for over 1 month. Over a 12-month period, he improved to
      walking with a quad cane, but he required self-catheterization. Although numerous
      factors were considered, neurotoxicity of 2% lidocaine solution has been
      discussed as the potential cause. We were unable to find any other factors that
      could have caused the cauda equina syndrome.

PMID- 9526942
TI  - Massive air embolism: a case report.
AB  - We describe a case where massive air embolism occurred while infusing fluid under
      pressure with a pressurized infusion system, with fluid bags which contained
      volumes of air from the manufacturer. We suggest that anesthesiologists be
      meticulous in de-airing the infusion bag before connecting it to the intravenous
      infusion system. Also, if the manufacturers of crystalloid solutions would
      produce their product devoid of air, then this inherent risk would be
      substantially decreased.

PMID- 9526943
TI  - In initio invadere: issues in infant informed consent, i.v.s, and intubation.

PMID- 9526944
TI  - Management of perioperative pain in hospitalized patients: a national survey.
AB  - A survey was carried out to provide "benchmark" data on current practices of in
      hospital perioperative pain management. The 59-item survey questionnaire
      incorporated all key points contained in the Agency for Health Care Policy and
      Research and the American Society of Anesthesiologists published guidelines
      concerning institutional policies as well as practice patterns. The questionnaire
      was mailed to designated pain specialists in a sample of 400 hospitals that were
      systematically stratified by bed size and geographic region. Of the 400
      questionnaires mailed, 223 (56%) were returned. Of the 223 respondents, 85% were
      board-certified anesthesiologists. There was good to excellent overall adherence
      to most of the guideline recommendations; significant exceptions were the
      infrequent use of nonpharmacologic techniques for pain control and the relatively
      high frequency of intramuscular opioid use. In general, large hospitals have a
      greater adherence to the recommendations of the guidelines than do smaller
      hospitals. No noteworthy variations in institutional policies or practice
      patterns were evident. These results provide comprehensive baseline data against
      which future developments in the field of perioperative pain management can be
      assessed.

PMID- 9526945
TI  - Unnecessary autologous donation and hemodilution for low blood loss procedures.

PMID- 9526946
TI  - Mechanisms involved in the antiplatelet activity of tetramethylpyrazine in human
      platelets.
AB  - Tetramethylpyrazine is the active ingredient of a Chinese herbal medicine. In
      this study, tetramethylpyrazine was tested for its antiplatelet activities in
      human platelet suspensions. In human platelets, tetramethylpyrazine (0.5-1.5 mM)
      dose-dependently inhibited both platelet aggregation and ATP-release reaction
      induced by a variety of agonists (i.e., ADP, collagen, and U46619).
      Tetramethylpyrazine (0.5 mM) did not significantly change the fluorescence of
      platelet membranes labeled with diphenylhexatriene, even at the high
      concentration (1.5 mM). Furthermore, tetramethylpyrazine (0.5-1.5 mM) dose
      dependently inhibited [3H]inositol monophosphate formation stimulated by collagen
      (5 microg/ml) in [3H]myoinositol loaded platelets. Tetramethylpyrazine (0.5-1.5
      mM) also dose-dependently inhibited the intracellular free Ca2+ rise of Fura 2-AM
      loaded platelets stimulated by collagen (5 microg/ml). Moreover,
      tetramethylpyrazine (0.5-1.5 mM) inhibited thromboxane B2 formation stimulated by
      collagen. At a higher concentration (1.0 mM), tetramethylpyrazine has also been
      shown to influence the binding of FITC-triflavin to platelet glycoprotein
      IIb/IIIa complex. Triflavin, a specific glycoprotein IIb/IIIa complex antagonist
      purified from Trimeresurus flavoviridis venom. It is concluded that the
      antiplatelet activity of tetramethylpyrazine may possibly involve two pathways:
      1) at a lower concentration (0.5 mM), tetramethylpyrazine is shown to inhibit
      phosphoinositide breakdown and thromboxane A2 formation; and 2) at a higher
      concentration (1.0 mM), it leads to the inhibition of platelet aggregation
      through binding to the glycoprotein IIb/IIIa complex.

PMID- 9526947
TI  - Effect of glycoprotein IIb/IIIa antagonists on the HIT serum induced activation
      of platelets.
AB  - Heparin-induced thrombocytopenia is an increasingly common side effect associated
      with heparin usage. In the more severe manifestation of the syndrome, patients
      can develop thrombosis; a 10% mortality is associated with heparin induced
      thrombocytopenia. To date, the therapeutic options for patients with heparin
      induced thrombocytopenia are limited. Glycoprotein IIb/IIIa inhibitors have been
      shown to block platelet aggregation induced by a wide variety of agonists. The
      ability of antibody and synthetic small molecule inhibitors of glycoprotein
      IIb/IIIa to block in vitro activation and aggregation of platelets in response to
      heparin-induced thrombocytopenia positive serum/heparin was examined using flow
      cytometry, platelet aggregometry, and luminescence aggregometry. Abciximab, YM
      337, and SR 121566A were each found to inhibit platelet microparticle formation
      and P-selectin expression in whole blood, in response to heparin-induced
      thrombocytopenia positive serum/heparin. In a platelet rich plasma system, the
      platelet aggregation response was inhibited by all three agents. The IC50 for
      inhibition of heparin-induced thrombocytopenia positive serum/heparin induced
      platelet aggregation by SR 121566A was 18 nM, a concentration which was 4 to 8
      fold lower than that observed for collagen and arachidonic acid induced
      aggregation. Adenosine triphosphate release from activated platelets, as measured
      by luminescence aggregometry, was concentration-dependently inhibited by SR
      121566A. These results suggest that glycoprotein Ilb/IIIa inhibitors may be
      beneficial in the management of heparin-induced thrombocytopenia and warrant
      further investigation.

PMID- 9526948
TI  - Enhanced blood coagulation and enhanced fibrinolysis during hemodialysis with
      prostacyclin.
AB  - In the present study the effect of unfractionated heparin (UFH) (Liquemin, 750
      1000 IU/h), low molecular weight heparin (LMWH) (Fragmin, 3000-7250 IU bolus),
      and prostacyclin (Flolan, 5 ng/kg body weight/min) on the activation of blood
      coagulation and fibrinolysis, induced by polysulfone membrane dialyzers during
      hemodialysis, was compared. Plasma levels of thrombin-antithrombin III complex
      (TAT), fibrin split product D-dimer, and plasmin-plasmin inhibitor-complex (PPI)
      were measured in the arterial and venous line of the dialyzer at the beginning
      and at 10, 60, 120, and 180 minutes of hemodialysis. Five patients on chronic
      hemodialysis treatment were investigated in a cross over study. Clinically all
      three anticoagulation regimen were sufficient for hemodialysis treatment. Using
      UFH or LMWH TAT, PPI, and D-dimer levels were similar in the venous and the
      arterial line of the dialyzer. However, during prostacyclin treatment the levels
      of these activation markers were significantly higher in the venous line. Based
      on these data the dialyzer membrane can be considered as a site of activation of
      blood coagulation and of fibrinolysis during anticoagulation with prostacyclin in
      hemodialysis.

PMID- 9526949
TI  - Evaluation of the combination of a bedside D-dimer assay and enzyme-linked
      immunosorbent soluble fibrin assay in patients with suspected venous
      thromboembolism.
AB  - The objectives of the study were to determine whether the combination of a
      negative SimpliRED D-dimer assay and a low soluble fibrin result reliably
      excludes venous thromboembolism, and whether patients with proven venous
      thromboembolism and a normal SimpliRED D-dimer have evidence of impaired
      fibrinolysis. The study was a retrospective analysis of a cohort of 262
      consecutive patients, 94 patients presenting with suspected deep venous
      thrombosis and 168 with suspected pulmonary embolism. Fifty-nine patients (22.5%)
      were classified as venous thromboembolism-positive, 27 with pulmonary embolism,
      and 32 with deep venous thrombosis. One hundred and fourteen patients (43.5%) had
      SimpliRED D-dimer and a soluble fibrin result of less than or equal to 2.0
      microg/ml; the negative predictive value was 98.2% (95% confidence interval: 93.8
      99.8%), and the likelihood ratio was 0.06. Eight patients with proven venous
      thromboembolism had a negative SimpliRED D-dimer; all had elevated ELISA D-dimer
      levels and six had elevated soluble fibrin levels. This suggests that patients
      with venous thromboembolism and a normal SimpliRED result do not have impaired
      fibrinolysis as a cause of their false-negative result. This study suggests that
      the combination of SimpliRED and soluble fibrin can be used to exclude venous
      thromboembolism in over 40% of patients who present with a clinical suspicion of
      deep venous thrombosis or pulmonary embolism and that the small group of patients
      with venous thromboembolism and a normal SimpliRED do not have impaired
      fibrinolysis.

PMID- 9526950
TI  - Thrombin reduces large heparan sulfate proteoglycan molecules in cultured
      vascular endothelial cell layers through inhibition of core protein synthesis.
AB  - We investigated the alteration of heparan sulfate proteoglycans induced by
      thrombin in cultured vascular endothelial cells. Heparan sulfate proteoglycans,
      which were metabolically labeled with [3H] glucosamine and [35S] sulfate, were
      isolated by DEAE-Sephacel ion-exchange chromatography and characterized by
      molecular sieve gel filtration. Core proteins were analyzed by sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis of [35S] amino acids-labeled heparan
      sulfate proteoglycans after digestion with hepartinase. It was revealed that the
      high molecular weight subclass of heparan sulfate proteoglycans in the cell layer
      was markedly decreased by thrombin without changes of the hydrodynamic size of
      the molecules and the molecular weight of heparan sulfate chains. In addition,
      thrombin decreased the amount of large heparan sulfate proteoglycan core protein
      with a molecular weight of approximately 400 kDa, probably perlecan core, in the
      cell layer and the conditioned medium. The present data suggest that thrombin
      induced decrease in the amount of heparan sulfate in vascular endothelial cell
      layer includes a reduction of the number of large heparan sulfate proteoglycan
      perlecan molecules through a suppression of the core protein synthesis.

PMID- 9526951
TI  - Purification and characterization of multisquamase, the prothrombin activator
      present in Echis multisquamatus venom.
AB  - The venom of Echis multisquamatus (Central Asian sand viper) contains a single
      prothrombin activator, designated multisquamase, which is structurally and
      functionally different from ecarin, the prothrombin activator from the venom of
      Echis carinatus (saw-scaled viper). Multisquamase is comprised of a 58000 Mr and
      a 23000 Mr subunit that consists of two disulfide-linked chains of 12000 Mr and
      10000 Mr, respectively. In contrast to ecarin, which activates prothrombin and
      prethrombin 1 at comparable rates, and whose activity is hardly affected by Ca2+
      or by changes in ionic strength, multisquamase hardly activates prethrombin 1;
      prothrombin activation requires Ca2+ and is strongly inhibited at high ionic
      strength. The most favourable kinetic parameters are observed at 1 mM Ca2+ and at
      low ionic strength (Km=0.085 microM and kcat=0.68 s(-1) at I approximately 0.04).
      An increase in ionic strength considerably reduces the rate of prothrombin
      activation, due to an increase of the Km (Km=0.8 microM and kcat=1.03 s(-1) at I
      approximately 0.2). Studies in plasmas from patients on oral anticoagulant
      therapy show that E. Multisquamatus venom only activates carboxylated
      prothrombin, whereas E. carinatus activates both prothrombin and
      descarboxyprothrombin. Thus, multisquamase-dependent prothrombin activation
      appears to require post-translational modification of the gla-domain. This venom
      prothrombin activator may, therefore, become a useful tool to quantitate
      prothrombin and descarboxyprothrombin in cases where vitamin K-dependent
      carboxylation of prothrombin is impaired.

PMID- 9526952
TI  - Platelet activation with combination of ionophore A23187 and a direct protein
      kinase C activator induces normal secretion in patients with impaired receptor
      mediated secretion and abnormal signal transduction.
AB  - Defects in signal transduction mechanisms may underlie the impaired aggregation
      and secretion in patients with congenital platelet function defects (CPD). Both
      protein kinase C (PKC) induced pleckstrin phosphorylation and cytoplasmic Ca2+
      mobilization play a major role in secretion. We postulated that combined platelet
      activation with a cell permeable direct PKC activator 1,2-dioctanoyl-sn-glycerol
      (DiC8) and ionophore A23187, which possibly bypass the steps involved in the
      intracellular synthesis of two major mediators (inositol trisphosphate,
      diacylglycerol), may induce normal dense granule secretion in patients with
      impaired receptor mediated secretion. We studied eight CPD patients with abnormal
      aggregation and secretion in response to several different surface receptor
      mediated agonists despite the presence of normal dense granule contents. Receptor
      mediated Ca2+ mobilization and/or pleckstrin phosphorylation were abnormal in
      seven patients. Platelet activation with a combination of ADP (8 microM) with
      DiC8 (200 microM) or A23187 (10 microM) improved secretion in four patients.
      However, platelet activation with a combination of 200 microM DiC8 with 10 microM
      A23187, or 100 microM DiC8 with 5 microM A23187 induced normal secretion in
      platelet-rich plasma in all patients. These studies suggest that in such patients
      with CPD the ultimate process of exocytosis or secretion per se is intact and
      impaired secretion results from abnormalities in early signal transduction
      events, possibly upstream of diacylglycerol formation and calcium mobilization.
      Detailed studies are needed to delineate the specific abnormalities in these
      heterogenous patients with signal transduction defects.

PMID- 9526953
TI  - The molecular markers of hemostatic activation on coronary artery disease.
AB  - Endothelial cells, circulating platelets, and proteins of the coagulation and
      fibrinolytic systems are known to contribute to the hemostatic processes. Various
      molecular markers of hemostatic alteration are found in increased amounts in the
      circulation during the activation of this process. In this study, we investigated
      serum lipoprotein (a) and plasma platelet factor 4, beta-thromboglobulin,
      thrombin-anthithrombin complex, fibrinopeptid A, D-dimer, tissue plasminogen
      activator, tissue plasminogen activator inhibitor, and fibronectin levels in
      patients with coronary artery disease. The levels of all these markers were found
      to be significantly higher as compared to the control group. Our findings suggest
      that patients with coronary artery disease have greater blood coagulability than
      controls, and the use of molecular markers has become greatly important in
      clinical practice.

PMID- 9526954
TI  - Structure-function studies on the inhibition of binding of alpha-thrombin to
      platelet GpIb alpha by the peptide D-Y-Y-P-E and the artifactual inhibitory
      activity of C-terminal E in this peptide.

PMID- 9526955
TI  - Prothrombin Marburg--a dysfunctional coagulation protein.

PMID- 9526956
TI  - Myths and realities of P-selectin plasma levels in patients with acute myocardial
      infarction.

PMID- 9526957
TI  - Platelet hypoaggregability in hereditary hypertriglyceridemic rats: relation to
      plasma triglycerides.
AB  - To define better the relationships between lipid metabolism disturbances and
      platelet aggregation we have examined these parameters in hereditary
      hypertriglyceridemic and control Lewis rats. Hereditary hypertriglyceridemic rats
      are hypertensive and have high plasma triglycerides but not elevated plasma total
      cholesterol. In the present study, we have demonstrated that platelets from
      hereditary hypertriglyceridemic rats have lowered initial rate and maximal
      aggregation after stimulation with thrombin or ADP in comparison with controls.
      These two strains did not differ significantly in the inhibition of platelet
      aggregation by the thromboxane A2 receptor inhibitor, SQ 29 548. In hereditary
      hypertriglyceridemic rats, the thrombin response, as well as the contribution of
      the thromboxane A2-sensitive pathway, were positively associated with the plasma
      level of triglycerides. Similar trend was found in Lewis rats. However, the
      slopes of these relationships were reduced in hereditary hypertriglyceridemic
      rats. These alterations of the aggregatory responses in hereditary
      hypertriglyceridemic rats were independent of blood pressure and plasma
      cholesterol level. In conclusion, our results showed a clear-cut platelet
      hypoaggregability to both thrombin and ADP in hypertensive hypertriglyceridemic
      rats. This hypoaggregability was not due to an impaired function of the
      thromboxane A2 pathway but could be connected with disturbances of lipid
      metabolism.

PMID- 9526958
TI  - Longer aPTT values in healthy children than in adults: no single cause.
AB  - We have shown that activated partial thromboplastin time values in children are
      considerably longer than in adults, but the causes for this observation remained
      unclear. Therefore, we investigated the correlation between activated partial
      thromboplastin time values and concentrations of clotting factors, quotients and
      titers of the tissue thromboplastin inhibition test, and antiphospholipid
      antibodies in healthy children, children with recurrent infections, and adults.
      Concentrations of factors VIII, IX, and HMWK were significantly lower in children
      than in adults. Simple linear regression analysis failed to show a correlation
      between the concentration of a single clotting factor and the activated partial
      thromboplastin time values. No significant correlation was found between
      activated partial thromboplastin time and elevation of the tissue thromboplastin
      inhibition test quotients or titers, or antiphospholipid antibodies values. The
      determined activated partial thromboplastin time was best described by a function
      including all measured coagulation factors. Our study suggests, that no single
      clotting factor or lupus anticoagulants are responsible for the longer activated
      partial thromboplastin time in healthy children, but that activated partial
      thromboplastin prolongation is caused by the combination of several slightly
      lower clotting factors.

PMID- 9526959
TI  - Homocysteinemia and endothelial damage after methionine load.
AB  - Homocysteinemia increased significantly after a methionine load of 50 mg/kg in
      patients with peripheral artery occlusive disease but this load was insufficient
      to increase circulating endothelial cell count as a marker of endothelial damage.
      Only after an increased load of 100 mg/kg methionine circulating endothelial
      cells also increased markedly confirming the results of a previous experimental
      study. These data indicate a threshold concentration of homocysteine in blood
      necessary to induce endothelial lesions.

PMID- 9526960
TI  - Reversible acylation of factor Xa as a potential therapy for hemophilia.
AB  - Current therapies for treatment of hemophilia A involve infusion of factor VIII,
      but are ineffective for patients who develop inhibitory antibodies. We have
      previously proposed that bypassing the intrinsic pathway (VIIIa/IXa) with
      reversibly acylated factor Xa offers an improvement on existing therapies as it
      provides a time-dependent release of procoagulant activity without the addition
      of factors VIII or IX. The present study was designed to determine the effect of
      substituted 4-amidinophenyl benzoates on the acylation of factor Xa, as well as
      the subsequent deacylation rates of the resulting acyl Xa. A subset of this
      series of acyl Xa's were incorporated into the prothrombinase complex and
      recovery of catalytic activity was measured by activation of prothrombin to
      thrombin. Similarly, some acyl Xa's were also evaluated for their capacity to
      enhance clotting times of human plasma. Our study indicates that by choosing the
      appropriate acyl Xa, the time course of factor Xa regeneration can be modulated
      extensively. Animal studies will be required to show that the use of acyl Xa as a
      procoagulant agent is feasible in an in vivo system.

PMID- 9526961
TI  - Urokinase localization and activity in isolated eosinophils.
AB  - Urokinase-type plasminogen activator is implicated in cell invasion and
      migration. In this study, we provide evidence for the presence of urokinase-type
      plasminogen activator (3.5 +/- 1.5 ng/mg of cell protein) in isolated peripheral
      blood eosinophils, in comparison to 6.7 +/- 2.3 ng/mg of protein in neutrophils.
      Both immunocytochemical and immunogold staining of urokinase-type plasminogen
      activator on electron microscopy showed its localization in granules of resting
      cells. Mild stimulation by platelet-activating factor induced a translocation of
      urokinase-type plasminogen activator from the granules to the cell membrane and a
      formation of urokinase-type plasminogen activator capping, suggesting a role for
      urokinase-type plasminogen activator in eosinophil migration. The activation of
      eosinophils led to the release of factor(s) which, after activation of pro
      urokinase-type plasminogen activator, induced an inactivation of generated
      urokinase-type plasminogen activator. Our results suggest that urokinase-type
      plasminogen activator is implicated in activated eosinophils invasiveness because
      the exposure of urokinase-type plasminogen activator is regulated both in space
      and time.

PMID- 9526962
TI  - Compaction as a method to characterise fibrin network structure: kinetic studies
      and relationship to crosslinking.
AB  - While it has been shown that compaction is inversely correlated to the Young's
      modulus of elasticity of the network and to the final strength at break, the
      relationship between collapsibility of the network subjected to a standardised
      centrifugal force and the degree of crosslinking (i.e., compaction) has not been
      properly addressed. Three sets of networks developed from plasma and pure
      fibrinogen solution, with varying degree of crosslinking induced by the addition
      of different amounts of calcium, were subjected to centrifugation at 8000g. In
      networks developed from plasma, compaction correlated with the degree of
      crosslinking. Whilst totally crosslinked clots were most resistant to collapse,
      partially crosslinked clots were far less resistant to collapse. In purified
      fibrinogen, however, the effect crosslinking was all or nothing. Both totally
      crosslinked and partially crosslinked clots were equally resistant to collapse.
      Calcium induced crosslinking provides fibrin with the required strengthening of
      the fibrin network. However, there are also fibre to fibre interactions as can be
      observed in networks developed in the presence of drugs like gliclazide.
      Compaction is a simple technique which can be used in any clinical laboratory to
      characterise the degree of crosslinking and also the tensile properties of the
      network.

PMID- 9526963
TI  - Warfarin analog inhibition of human CYP2C9-catalyzed S-warfarin 7-hydroxylation.
AB  - Human metabolism of the S-warfarin enantiomer is catalyzed primarily by
      cytochrome P4502C9 (CYP2C9), which, because of the enzyme's broad drug substrate
      specificity, leads to drug-S-warfarin interactions. Several warfarin analogs have
      been synthesized and used to determine whether they exhibit diminished
      interactions with CYP2C9. The kinetics of the warfarin analogs' inhibition of
      human liver microsomal CYP2C9 catalyzed metabolism of S-warfarin to S-7
      hydroxywarfarin have been investigated. R- and S-7-fluorowarfarin were both
      predominantly competitive inhibitors, whereas racemic 6-fluorowarfarin and
      racemic 6,7,8-trifluorowarfarin were predominantly mixed inhibitors with some
      competitive inhibition. For the alcohols produced by reductive methylation of the
      side chain of R- and S-warfarin, the R-enantiomer did not inhibit S-warfarin
      metabolism, whereas the S-enantiomer was primarily a competitive inhibitor. The
      fluorine substituted warfarins and the S-warfarin alcohol apparently bind with
      high affinity to CYP2C9. Thus their use clinically (if efficacious) would not
      prevent CYP2C9 associated warfarin-drug interactions. The R-warfarin alcohol did
      not inhibit CYP2C9 catalyzed metabolism of S-warfarin and is less likely than
      warfarin to participate in CYP2C9 associated warfarin-drug interactions.

PMID- 9526964
TI  - Sibutramine reduces food intake in non-dieting women with obesity.
AB  - Sibutramine (SIB), an inhibitor of serotonin and noradrenaline reuptake, has been
      shown in clinical trials to be associated with a dose-related decrease in
      bodyweight. This double-blind, placebo-controlled, Latin square crossover study
      examined whether the effect on bodyweight could be due in part to a reduction in
      daily food intake. Twelve non-dieting, women with obesity (body mass index of
      30.5 to 41.9) received three treatments (0 [matching placebo], 10, or 30 mg
      SIB/day) for 14 days, with 14-day washout periods in between. On days 7 and 14,
      participants came to the laboratory to eat breakfast, lunch, and dinner so that
      daily energy and macronutrient intakes and ratings of hunger and satiety could be
      measured. Significant reductions occurred in food intake (both grams and energy)
      over the 14-day study period. On day 7, SIB 30 reduced intake significantly by
      1762 kJ (23% reduction from placebo), and on day 14, both SIB 10 and SIB 30
      significantly reduced intake compared with placebo (SIB 10, 19% reduction [1490
      kJ]; SIB 30, 26% reduction [2079 kJ]). On day 7, the percentage of energy
      consumed from carbohydrate increased significantly with the 30-mg dose (56.7%)
      compared with that of placebo (51.4%), with a reciprocal decrease in energy from
      fat (27.8% to 24%). The results show that SIB reduced energy intake in women with
      obesity who were not attempting to lose weight.

PMID- 9526965
TI  - Body anthropometry and the risk of hip and wrist fractures in men: results from a
      prospective study.
AB  - Available epidemiological information on the associations between body
      anthropometry and the incidence of fractures in men is limited. We therefore
      prospectively investigated the association between body anthropometry and the
      incidence of hip and wrist fractures from low and moderate trauma among 43,053
      men who were 40 years to 75 years of age in 1986 when they first enrolled in the
      Health Professionals Follow-Up Study. After 8 years of follow-up, 201 wrist
      fracture cases and 56 hip fracture cases were reported. Greater height was
      associated with significant elevations in both hip and wrist fractures, whereas
      nonsignificant inverse associations were observed with weight and body mass
      index. Men in the highest quintile of waist circumference had a relative risk
      (RR) of 2.57 (95% confidence interval [CI] 0.64 to 10.3) for hip fracture and
      2.05 (95% CI 1.06 to 3.96) for wrist fracture when compared with men in the
      lowest quintile. Waist-to-hip ratio was also positively related to fracture
      incidence; comparing highest with lowest quintile, the RRs were 3.92 (95% CI 1.07
      to 14.3) for hip fracture and 1.50 (95% CI 0.85 to 2.66) for wrist fracture.
      These anthropometric indicators, in particular waist-to-hip ratio, may be useful
      for the prediction of hip fracture in adult men.

PMID- 9526966
TI  - The effect of dehydroepiandrosterone combined with a low-fat diet in
      spontaneously obese dogs: a clinical trial.
AB  - Dehydroepiandrosterone (DHEA) has been shown to have antiobesity activity in
      rodents and spontaneously obese dogs. This study evaluated the effect of DHEA or
      placebo combined with a low-fat/high-fiber diet in spontaneously obese dogs in a
      clinical trial. Spontaneously obese, euthyroid dogs, referred to the University
      of Wisconsin School of Veterinary Medicine for treatment of their obesity, were
      evaluated for percent overweight, rate of weight loss, serum cholesterol, plasma
      lipoprotein and serum biochemistry profiles, complete blood count, and endocrine
      profiles (T4, T3, cortisol, insulin, and DHEA-sulfate). DHEA-treated dogs had a
      significantly increased rate of actual and percent excess weight loss compared
      with placebo-treated dogs. Serum cholesterol decreased in both treatment groups;
      however, DHEA-treated dogs had a significantly greater reduction than placebo
      treated dogs. DHEA-treated dogs had a significant 32% reduction in total plasma
      cholesterol, which was due to a 27% reduction in the lipoprotein fraction
      containing the high-density lipoprotein (HDL) and a 50% reduction in the
      lipoprotein fraction containing the low-density lipoprotein (LDL). Placebo
      treated dogs did not have a significant reduction in total plasma cholesterol or
      in the fraction containing LDL; however, they did have a significant 11%
      reduction in the fraction containing HDL. Significant decreases in serum T4 and
      T3 observed in dogs receiving DHEA were not noted in dogs receiving placebo. DHEA
      in combination with caloric restriction results in a faster rate of weight loss
      than does caloric restriction alone. In addition, DHEA has hypocholesterolemic
      activity, particularly affecting the lipoprotein fraction containing the LDL
      cholesterol.

PMID- 9526967
TI  - Food intake in Prader-Willi syndrome and controls with obesity after
      administration of a benzodiazepine receptor agonist.
AB  - Benzodiazepine receptor (BZR) agonists, used extensively for their anxiolytic
      effects, have been shown to increase food intake in many mammalian species.
      Little information, however, is available on the effects of BZR agonists on
      feeding behaviors of humans. Food intake was evaluated in a 60-minute free
      feeding standardized test after the acute administration of the BZR agonist
      chlordiazepoxide (CDP, Librium; 5 mg or 20 mg) or placebo. Subjects were 12
      individuals with the Prader-Willi syndrome (PWS), a disorder characterized by
      extreme hyperphagia and morbid obesity, and 11 controls with obesity. PWS
      subjects showed the characteristic hyperphagia associated with the appetite
      disorder, consuming more than six times as many sandwiches as controls with
      obesity. Results revealed no significant effect of either dose of CDP on the food
      intake of either group. Serum assays revealed that dose-dependent, clinically
      effective levels of CDP and active metabolites were achieved. These results
      suggest that acute administration of the BZR agonist CDP, at the therapeutic
      levels used, may not increase food intake in populations with obesity. However,
      the chronic effects of CDP on appetite in human populations still need to be
      explored.

PMID- 9526968
TI  - Differential short-term distribution of estrone and oleoyl-estrone administered
      in liposomes to lean and obese Zucker rats.
AB  - Thirteen-week-old female Zucker lean (Fa/Fa) and obese (fa/fa) rats were injected
      through a cannula inserted in the left jugular vein with 1 mL/kg of 3H-labeled
      oleoyl-estrone in liposomes (Merlin-2) (i.e., 670 fmol, 84 kBq). The rats were
      killed 10 minutes later and dissected. The presence of intact or hydrolyzed
      oleoyl-estrone was later determined in all samples. The pattern of distribution
      of estrone was quite different from that of oleoyl-estrone both in rats that were
      lean and in those that were obese. Estrone was better retained by white adipose
      tissue than oleoyl-estrone. Liver, spleen, and lungs accumulated more oleoyl
      estrone and split part of it, from 4.7% (lung, obese) to 27% (liver, lean). The
      overall high retention of estrone by the rat tissues results in its very low
      circulating levels. The fast splitting of liposome-carried oleoyl-estrone by most
      tissues (up to more than 67% by intestine and skin of lean rats) may help explain
      the rise in blood free estrone. The differences between lean and obese Zucker
      rats are mainly quantitative in the case of estrone, the main differences being
      found in blood and adipose tissues. However, when we compare the data for oleoyl
      estrone, the differences cannot be dismissed simply as due to differences in body
      size or the extent of fat deposits. A large portion of the label remained in the
      blood of the rats that were obese but not in those that were lean, the tissues of
      which took up more label. Brown adipose tissue shows a fair affinity for oleoyl
      estrone in the rats that were lean but practically does not retain label in the
      rats that were obese, suggesting that oleoyl-estrone may have a direct effect on
      brown adipose tissue. The decreased uptake of oleoyl-estrone in rats that were
      obese shows that the mechanism regulating the turnover or disposal of this signal
      is altered in this type of genetic obesity.

PMID- 9526969
TI  - The relationship between fat distribution and coronary risk factors in sedentary
      postmenopausal women on and off hormone replacement therapy.
AB  - The purpose of this study was to examine the relationship between fat
      distribution and coronary risk factors (CRF) in sedentary overweight
      postmenopausal women both on and off hormone replacement therapy (HRT). Medical
      records and information were abstracted from nonsmoking women entering a weight
      loss program. A total of 33 women on HRT (mean age=50.12+/-5.2) and 51 nonusers
      (mean age=52.52+/-7.8) fulfilled subject eligibility requirements and were
      included in the data analysis. Results showed a significantly lower waist-to-hip
      ratio (WHR) (p=0.009) and waist (p=0.010) and greater levels of high-density
      lipoprotein cholesterol (HDL-C) (p=0.035) in HRT users than in nonusers. After
      converting correlations to standard Z-scores and performing z-tests, the
      correlation between total cholesterol (T-Chol) and WHR was significantly greater
      in nonusers than in HRT users (p=0.038). A multiple regression analysis showed
      differences between groups in the ability of age and anthropometric variables to
      predict CRF. Although T-Chol could be predicted in nonusers (r2=0.24; p=0.011),
      very low-density lipoprotein cholesterol (VLDL-C) and systolic blood pressure
      (SBP) could be significantly predicted in HRT users only (r2=0.28, p=0.055 and
      r2=0.40, p=0.005 for VLDL-C and SBP, respectively). These data suggest that there
      are differences between HRT users and nonusers in predictors of CRF, central
      adiposity, HDL-C, and the relationship between WHR and T-Chol. It is concluded
      that the significantly lower levels of central adiposity observed in HRT users
      may have clinical benefits with regard to CRF.

PMID- 9526970
TI  - Metformin decreases food consumption and induces weight loss in subjects with
      obesity with type II non-insulin-dependent diabetes.
AB  - Metformin often promotes weight loss in patients with obesity with non-insulin
      dependent diabetes mellitus (NIDDM). The mechanism may be attributed to decreased
      food intake. This study has tested the effect of metformin on satiety and its
      efficacy in inducing weight loss. Twelve diet-treated NIDDM women with obesity
      were randomly given two dose levels (850 mg or 1700 mg) of metformin or placebo
      at 0800 for three consecutive days followed by a meal test on the third day on
      three occasions using a 3x3 Latin square design. The number of sandwich canapes
      eaten in three consecutive 10-minute periods beginning at 1400 hours was used to
      quantitate food intake, and the level of subjective hunger was rated just before
      the sandwich meal with a linear analogue hunger rating scale at 1400 after a 6
      hour fast. The prior administration of metformin produced a reduction in calorie
      intake after each of the two doses of metformin treatment. The 1700-mg metformin
      dose had the most marked appetite suppressant action. Similarly, hunger ratings
      were significantly lowered after metformin, and the effect was most pronounced
      after the administration of 1700 mg of metformin. To assess the efficacy of
      metformin in reducing bodyweight, 48 diet-treated NIDDM women with obesity who
      had failed to lose weight by diet therapy were first placed on a 1200-kcal ADA
      (American Diabetes Association) diet before being randomized to receive either
      metformin (850 mg) or placebo twice daily in a double-blind fashion for 24 weeks.
      A 4-week single-blind placebo lead-in period preceded and a 6-week single-blind
      placebo period followed the 24-week double-blind treatment period. Subjects
      treated with metformin continued to lose weight throughout 24 weeks of treatment;
      their mean maximum weight loss was 8 kg greater than that of the placebo group,
      with corresponding lower HbA1C and fasting blood glucose levels at the end of the
      active treatment period. These results indicate that metformin decreases calorie
      intake in a dose-dependent manner and leads to a reduction in bodyweight in NIDDM
      patients with obesity.

PMID- 9526971
TI  - Effects of enterostatin on consumption of optional foods in non-food-deprived
      rats.
AB  - Enterostatin, the activation peptide of procolipase, has been reported to reduce
      high-fat food consumption in rats. This reduction has been reliably demonstrated
      using procedures in which the test diet was also the maintenance diet of the
      animals. Other reports, though, have shown that peripherally administered
      enterostatin had no effect on the consumption of oil provided as an option to the
      diet, and that centrally administered enterostatin had no effect on the
      consumption of an optional high-fat mixed food. However, the effects of
      peripherally administered enterostatin on the consumption of an optional high-fat
      mixed food have not been examined. This experiment, then, examined the effects of
      peripherally administered enterostatin on the consumption of optional, mixed
      foods (no-fat and high-fat cookies) provided in addition to a standard diet under
      choice and nonchoice conditions. Four experiments were conducted. In experiment
      I, the effect of enterostatin in a two-choice feeding paradigm was assessed. In
      experiment II, the effect of enterostatin in a nonchoice feeding paradigm was
      assessed. In experiment III, the effect of enterostatin administered at five
      different pretreatment times in a non-choice feeding paradigm was assessed.
      Enterostatin had no effect on cookie intake in any of these experiments. Finally,
      experiment IV was undertaken to verify the activity of the peptide. Enterostatin
      significantly reduced the consumption of a standard diet in overnight food
      deprived rats, thus confirming the activity of the peptide used in experiments I
      to III. Enterostatin may not play a major role in the regulation of food intake
      that is stimulated by optional foods that are periodically provided in addition
      to a standard well-balanced diet.

PMID- 9526972
TI  - Realistic weight perception and body size assessment in a racially diverse
      community sample of dieters.
AB  - Recently, a shift in obesity treatment away from emphasizing ideal weight loss
      goals to establishing realistic weight loss goals has been proposed; yet, what
      constitutes "realistic" weight loss for different populations is not clear. This
      study examined notions of realistic shape and weight as well as body size
      assessment in a large community-based sample of African-American, Asian,
      Hispanic, and white men and women. Participants were 1893 survey respondents who
      were all dieters and primarily overweight. Groups were compared on various
      variables of body image assessment using silhouette ratings. No significant race
      differences were found in silhouette ratings, nor in perceptions of realistic
      shape or reasonable weight loss. Realistic shape and weight ratings by both women
      and men were smaller than current shape and weight but larger than ideal shape
      and weight ratings. Compared with male dieters, female dieters considered greater
      weight loss to be realistic. Implications of the findings for the treatment of
      obesity are discussed.

PMID- 9526973
TI  - Lactate production from glucose and response to insulin in perifused adipocytes
      from mesenteric and epididymal regions of lean and obese rats.
AB  - Lactate, an important metabolic substrate for peripheral tissues and the liver,
      is released in significant amounts from adipose tissue. Using a perifusion
      system, we measured lactate production from glucose and response to insulin in
      isolated mesenteric and epididymal adipocytes removed from fed or fasted male
      Wistar rats at two stages of growth and development: (a) lean rats (7 weeks to 9
      weeks old, weighing approximately 250 g), and (b) fatter rats (6 months to 8
      months old, weighing approximately 550 g). The results show that lactate
      production in perifused adipocytes is regulated by the prior nutritional state of
      the animals, by the adipose tissue region, and by the presence of insulin in the
      perifusate. In fat cells from lean rats, basal lactate production was
      significantly higher (p<0.05) in mesenteric cells when compared with epididymal
      cells, both in the fed state (7.8 nmo/10(7) fat cells per minute vs. 2.9
      nmol/10(7) fat cells per minute) and after 2 days of fasting (13.6 nmol vs. 3.5
      nmol). When the response to 1 mU/mL insulin was studied, however, the relative
      increase in lactate production produced by insulin was greater in the epididymal
      cells than in the mesenteric cells, in both the fed (194% vs. 91% over basal,
      respectively) and fasted (360% vs. 55% over basal, p<0.05) state. When larger
      epididymal adipocytes from fatter rats were compared with an equal number of
      smaller epididymal cells from leaner rats, the larger cells produced 4.99 nmol of
      lactate/10(7) fat cells per minute, whereas the smaller cells produced 2.93 nmol
      (p=0.08). Large fat cells showed a small and nonsignificant response to insulin
      in either type of cell (epididymal vs. mesenteric) or nutritional state (fed vs.
      fasted). This study indicates that distinct regional differences exist in lactate
      production and response to insulin. Mesenteric adipose tissue, which drains
      directly into the portal vein and provides substrates to the liver, may be an
      important source of lactate for the hepatic processes of gluconeogenesis and
      glycogenesis.

PMID- 9526974
TI  - The human obesity gene map: the 1997 update.
AB  - An update of the human obesity gene map incorporating published results up to
      October 1997 is presented. Evidence from Mendelian disorders exhibiting obesity
      as a clinical feature; single-gene mutation rodent models; quantitative trait
      loci uncovered in human genome-wide scans and in crossbreeding experiments with
      mouse, rat, and pig models; association and case-control studies with candidate
      genes; and linkage studies with genes and other markers is reviewed. All
      chromosomal locations of the animal loci are converted into human genome
      locations based on syntenic relationships between the genomes. A complete listing
      of all of these loci reveals that all but chromosome Y of the 24 human
      chromosomes are represented. Some chromosomes show at least three putative loci
      related to obesity on both arms (1, 2, 6, 8, 11, and 20) and several on one
      chromosome arm only (3p, 4q, 5q, 7q, 12q, 13q, 15q, 15p, 22q, and Xq). Studies
      reporting negative association and linkage results are also listed, with the
      exception of the unlinked markers from genome-wide scans.

PMID- 9526975
TI  - Management of petroclival meningiomas by stereotactic radiosurgery.
AB  - OBJECTIVE: To evaluate the role of stereotactic radiosurgery in the management of
      petroclival meningiomas, we retrospectively reviewed our experience with 62
      patients managed at the University of Pittsburgh during an 8-year period.
      METHODS: All patients had cranial base meningiomas involving the region between
      the petrous apex and the upper two-thirds of the clivus. Some tumors extended
      into the cavernous sinus. Each of 39 patients (63%) had previously undergone one
      or more attempts at surgical resection. Seven patients (11%) had received
      fractionated external beam radiation therapy. Using the gamma knife, conformal
      multiple isocenter radiosurgery was performed with tumor margin doses of 11 to 20
      Gy. RESULTS: During the median follow-up period of 37 months, neurological
      statuses improved in 13 patients (21%), remained stable in 41 patients (66%), and
      eventually worsened in 8 patients (13%). Tumor volumes decreased in 14 patients
      (23%), remained stable in 42 patients (68%), and increased in 5 patients (8%).
      Despite the proximity of these tumors to critical neural and vascular structures,
      complications resulting from radiosurgery were rare. Five patients (8%) developed
      new cranial nerve deficits within 24 months of radiosurgery, although none had
      evidence of tumor progression. These deficits resolved completely in two patients
      within 6 months of onset. CONCLUSION: Although an even longer follow-up period is
      desirable, we conclude that stereotactic radiosurgery provides a safe and
      effective management strategy for petroclival meningiomas, both as a primary
      procedure and as an adjunct to incomplete resection.

PMID- 9526976
TI  - Results of linear accelerator-based radiosurgery for intracranial meningiomas.
AB  - OBJECTIVE: We report the outcomes of patients treated with linear accelerator
      based radiosurgery for intracranial meningiomas at our institution. METHODS: We
      reviewed 127 patients with 155 meningiomas treated with stereotactic radiosurgery
      (SRS) at the study institutions between October 1988 and December 1995. RESULTS:
      There were 86 female and 41 male patients (median age, 61.5 yr; range, 19.9-87.9
      yr). The median follow-up period was 31 months (range, 1.2-79.8 mo). The median
      tumor volume was 4.1 cc (range, 0.16-51.2 cc), and the median marginal dose was
      15 Gy (range, 9-20 Gy). The tumor locations were as follows: convexity, 31
      tumors; parasagittal/falcine, 39 tumors; cranial base, 82 tumors; and
      ventricular/pineal, 3 tumors. There were 106 benign, 26 atypical, and 18
      malignant meningiomas and 5 cases of meningiomatosis. SRS was performed on 48
      lesions as the initial treatment and on 107 lesions as adjunct therapy. Freedom
      from progression was observed in 107 patients (84.3%) at a median time of 22.9
      months (range, 1.2-79.8 mo). Twenty patients (15.7%) had disease progression (16
      marginal [12.6%] and 4 local [3.1%]) at a median time of 19.6 months (range, 4.1
      69.3 mo); the median time for freedom from progression for the benign, atypical,
      and malignant meningiomas was 20.9, 24.4, and 13.9 months, respectively.
      Actuarial tumor control for the patients with benign meningiomas was 100, 92.9,
      89.3, 89.3, and 89.3% at 1, 2, 3, 4, and 5 years, respectively. Six patients
      (4.7%) had permanent complications attributable to SRS (median time, 10.3 mo;
      range, 4.3-18.0 mo); 13 patients died as a result of causes related to the
      meningiomas (median, 17.5 mo; range, 4.3-37.3 mo). The 1-, 2-, 3-, 4-, and 5-year
      survival probability for the entire group of patients was 90.3, 82.6, 73.6, 70.5,
      and 68.2%, respectively; for patients with benign meningiomas, excluding death
      resulting from intercurrent disease, the survival probability was 97.6, 94.8,
      91.0, 91.0, and 91.0%, respectively. The 1-, 2-, 3-, and 4-year survival
      probability for the patients with atypical and malignant meningiomas was 91.7,
      83.3, 83.3, and 83.3% and 92.3, 64.6, 43.1, and 21.5%, respectively. CONCLUSION:
      Even though complications from SRS are expected more frequently with large tumors
      near critical structures, SRS is a safe and effective means of treating selected
      meningiomas.

PMID- 9526977
TI  - Complications of craniofacial surgery for tumors involving the anterior cranial
      base.
AB  - OBJECTIVE: To evaluate the risk factors for postoperative complications among
      patients undergoing craniofacial resection for the treatment of anterior cranial
      base tumors, a retrospective analysis of patients treated in University of Tokyo
      Hospital between September 1987 and November 1996 was conducted. METHODS: Twenty
      nine patients underwent 33 craniofacial resections for tumors involving the
      anterior cranial base. Twenty-three of the 29 patients had malignant tumors and 6
      patients had benign tumors. Anterior craniofacial resection was performed using a
      combination of intracranial and extracranial approaches. Radiotherapy and
      neoadjuvant chemotherapy were administrated to some patients. RESULTS: Severe
      intracranial infections were more common among patients who underwent partial
      frontal lobectomies (P < 0.03). These infections occurred only in patients who
      had been treated previously with a craniotomy (P < 0.02) and a total radiation
      dose of > or =60 Gy (P = 0.06). Neither management of the extracranial structures
      nor methods of reconstruction of the cranial base showed significant correlation
      with major postoperative complications. CONCLUSION: Compared with previous
      reports, craniofacial resection has become a relatively safe and effective
      procedure for the treatment of tumors involving the anterior cranial base.
      However, additional care should be taken with patients who have experienced a
      previous craniotomy, frontal lobe involvement, or radiotherapy with a total dose
      of > or =60 Gy.

PMID- 9526978
TI  - Biodistribution of p-boronophenylalanine in patients with glioblastoma multiforme
      for use in boron neutron capture therapy.
AB  - OBJECTIVE: The success of boron neutron capture therapy depends on the safety and
      specificity of the boron delivery agent. As a preface to clinical boron neutron
      capture therapy of glioblastoma multiforme, a biodistribution study of
      intravenous p-boronophenylalanine (BPA) in patients undergoing craniotomy for
      resection of glioblastoma was performed. METHODS: Varying doses of intravenously
      administered BPA-fructose (130-250 mg BPA per kilogram of body weight) were given
      to patients 2 to 3 hours prior to the start of craniotomy for either suspected or
      known glioblastoma multiforme. Blood samples were collected over a 48-hour period
      for boron assay. At surgery, multiple samples of tumor, brain, and scalp were
      obtained for boron and histological analysis. RESULTS: Seventeen patients were
      studied; all but one had glioblastoma multiforme. No adverse effects from the BPA
      infusions were noted. The boron concentration in the blood reached a maximum at
      the end of the BPA infusion and was proportional to the administered dose of BPA.
      Normal brain concentrations of boron generally were equal to or less than that in
      blood. Tumor-blood boron ratios were highly variable: 1.6 +/- 0.8 (mean +/-
      standard deviation; n = 187; range, 0.3-3.5). The observed heterogeneity of BPA
      uptake in glioblastoma samples appears to correlate with the degree of
      cellularity observed on histological examination. CONCLUSION: Intravenous BPA
      administration up to a dose of 250 mg/kg is safe and well tolerated. BPA uptake
      in surgical samples of glioblastoma tissue is variable and may depend on the
      fraction of viable tumor cells in the individual sample. Further clinical studies
      using BPA as a boron delivery agent for boron neutron capture therapy of
      glioblastoma multiforme appear warranted.

PMID- 9526979
TI  - Choroid plexus carcinomas in childhood: clinical features and prognostic factors.
AB  - OBJECTIVE: Choroid plexus carcinomas are rare tumors with dismal prognosis. The
      role of surgery has been well established, but the benefit of either chemotherapy
      or radiotherapy remains controversial. To determine prognostic factors and
      effects of different therapeutic modalities on the outcome, we have reviewed the
      French experience of choroid plexus carcinoma. METHODS: Twenty-two children were
      registered in the Societe Francaise d'Oncologie Pediatrique between 1984 and
      1995. All these children underwent surgical resection of the primary tumor. The
      intent of postoperative treatment was to delay or to avoid radiation therapy.
      Nineteen children received postoperative treatment, with chemotherapy in 17 and
      radiation therapy in 2. Two responding patients underwent high-dose chemotherapy
      with stem cell rescue. RESULTS: The 5-year survival rate was 26%. The sole
      relevant prognostic factor was the extent of surgery. Patients with total or
      gross total resection had a 86% survival rate. Survival did not correlate with
      age, sex, delay between first appearance of symptoms and diagnosis, location of
      the primary tumor, tumor volume, or response to postoperative treatment. All but
      one patient with incomplete surgery had tumor recurrence within 2 to 23 months.
      CONCLUSION: Choroid plexus carcinoma has a very poor prognosis when surgery is
      incomplete. Aggressive surgical resection of the tumor is necessary for survival.
      Although chemotherapy gives promising responses, local control remains the main
      challenge, and "second look" surgery has to be considered for patients with
      incomplete resection.

PMID- 9526981
TI  - Hypertension, small size, and deep venous drainage are associated with risk of
      hemorrhagic presentation of cerebral arteriovenous malformations.
AB  - OBJECTIVE: To identify clinical and angiographic factors of cerebral
      arteriovenous malformations (AVMs) associated with hemorrhage to improve the
      estimation of the risks and help guide management in clinical decision making.
      METHODS: We conducted a retrospective analysis of 100 consecutive adults who have
      presented during the past 3 years to our institution with cerebral AVMs.
      Angiographic and clinical parameters were evaluated using multivariate logistic
      regression analysis to analyze factors associated with hemorrhagic presentation.
      RESULTS: The group had a mean age of 37.8 years; 53% were men, 48% presented with
      intracranial hemorrhage, and 40% presented with seizures. All 10 patients with
      cerebellar AVMs presented with hemorrhage. The following factors were
      independently associated with AVM hemorrhage: history of hypertension (P = 0.019;
      odds ratio [OR] = 5.36), nidal diameter <3 cm (P = 0.023: OR = 4.60), and deep
      venous drainage (P = 0.009: OR = 5.77). Dural arterial supply (P = 0.008; OR =
      0.15) was independently associated with decreased risk of bleed. Location, nidal
      aneurysms, patient age, and smoking were not associated with increased or
      decreased bleeding risk. CONCLUSION: In this study, we found small AVM size and
      deep venous drainage to be positively associated with AVM hemorrhage. Dural
      supply was associated with a decreased likelihood of hemorrhagic presentation.
      Hypertension was found to be the only clinical factor positively associated with
      hemorrhage, a finding not previously reported. Smoking, although associated with
      increased risk of aneurysmal subarachnoid hemorrhage, was not associated with a
      higher risk of AVM hemorrhage.

PMID- 9526980
TI  - Most intracranial meningiomas are not cleavable tumors: anatomic-surgical
      evidence and angiographic predictibility.
AB  - OBJECTIVE: The statement that intracranial meningiomas are cleavable tumors has
      to be seriously questioned from a surgical standpoint. The purpose of this study
      was 1) to analyze the operative reports of a personal series of meningiomas to
      evaluate the percentages of the tumors that could be dissected by passing in the
      extrapial plane (i.e., "cleavable") and of those in which the dissection had to
      be subpial (i.e., "noncleavable") and 2) to see whether preoperative angiography
      could help in predicting cleavability. METHODS: The series includes 150
      consecutive patients with intracranial meningiomas diagnosed with computed
      tomographic scans and explored preoperatively by selective external/internal
      carotid angiography, operated on using microsurgical techniques, and followed for
      more than 4 years. RESULTS: Dissection between tumor and underlying cortex could
      be achieved in the extrapial plane predominantly (i.e., on more than two-thirds
      of the interface) in only 54.6% of patients. On angiography, the pial-cortical
      arterial supply participated in at least equal part with the meningeal-dural
      arterial supply in vascularization of the tumor in 59.4% of patients. In this
      group, dissection could pass through the extrapial plane in only 34.8% of
      patients. Conversely, when meningeal-dural arterial supply was predominant on
      angiography, which occurred in 40.6% of patients, dissection could be achieved in
      the extrapial plane in 83.6% of patients. This difference is statistically
      significant (P < 0.001). CONCLUSION: Participation of pia mater in the vascular
      supply of intracranial meningiomas, and consequently, difficulty of dissection,
      can be predicted preoperatively on angiography. Knowledge of the arterial supply
      of the tumor before surgery is an important aid to the surgeon in preparing for
      and performing the operation.

PMID- 9526982
TI  - Detection of emboli after surgery for intracerebral aneurysms.
AB  - BACKGROUND: Neurological change after surgery for cerebral aneurysm caused by
      embolic events is commonly suspected, but direct detection of emboli has not been
      possible in the past. Transcranial Doppler ultrasound (TCD) is able to detect
      emboli, and large numbers of emboli detected in TCD studies have been associated
      with radiological changes and clinical deterioration. METHODS: During a 2-year
      period, 11 patients were observed to have emboli during routine TCD studies after
      aneurysm surgery. The computed tomographic (CT) scans of these patients were
      reviewed for low-density areas, suggesting ischemia. All patients studied during
      a 1-year interval (July 1995-July 1996) served as a control group and were
      reviewed for similar CT findings, and the two groups were compared using Fisher's
      exact test. RESULTS: Nine of the 11 patients (82%) observed to have emboli
      developed low-density areas on their CT scans, whereas 30 of the 123 (24%)
      patients without emboli developed low-density areas on their CT scans. The
      difference was significant (P < 0.001, Fisher's exact test). Credible sources for
      emboli were readily identified in each of the 11 patients. CONCLUSION: TCD allows
      detection of emboli after aneurysm surgery, and this detection is strongly
      associated with CT evidence of ischemia. Although detection of emboli was
      relatively rare in this study, rates of emboli occurrence may increase if
      systematic monitoring is used.

PMID- 9526983
TI  - Incidence of unsuspected blunt carotid artery injury.
AB  - OBJECTIVE: This study attempts to document the incidence of unsuspected blunt
      carotid artery injury (BCI) in a prospective series of consecutive blunt trauma
      patients undergoing angiographic evaluation of the aorta. Previous studies have
      included mainly patients who became symptomatic from BCI, thus documenting a
      "detected incidence." METHODS: During a 22-month period, all patients undergoing
      angiographic evaluation of the aorta after blunt trauma who were not felt to be
      at increased risk for BCI were included in the screening protocol. All patients
      initially suspected of BCI were studied outside the protocol. Angiographic
      evaluation of the carotid arteries was performed using nonselective contrast
      injections after aortic injury had been ruled out. RESULTS: The incidence of BCI
      among those patients screened under the protocol (n = 119) was 2.5% (3 of 119).
      Among all patients undergoing aortic evaluation at presentation (n = 171), the
      detected incidence of BCI was 3.5% (6 of 171). The detected incidence of BCI
      among all patients during the study period was 0.32% (10 of 3174). No risk
      factors for BCI were identified beyond the severity of trauma that led to aortic
      evaluation. CONCLUSION: The incidence of BCI found in those patients screened in
      this study, nearly 10 times the incidence of BCI in our blunt trauma population
      overall, suggests that these patients represent a subgroup on which to focus
      screening efforts, regardless of the diagnostic tools employed. The similarity
      between the angiographic incidence and the detected incidence of BCI in this
      study argues that few BCIs remain asymptomatic. All blunt trauma patients injured
      sufficiently to prompt aortic evaluation at presentation should be screened in
      some manner for BCI.

PMID- 9526984
TI  - Central nervous system infections after military missile head wounds.
AB  - OBJECTIVES: To evaluate variables instrumental in central nervous system
      infections after military missile head wounds, using uni- and multivariate
      analysis in 964 patients during the 8-year Iran-Iraq War. METHODS: Factors
      considered in this retrospective study were: the types of projectile, mode of
      injury, paranasal sinus involvement, number of lobes involved, transventricular
      injuries, place of exploration (base hospital or Nemazee Hospital), cerebrospinal
      fluid (CSF) fistulas, Glasgow Coma Scale (GCS) score, retained bone, and retained
      shell fragments. RESULTS: During the study period, 105 patients (11%) developed
      central nervous system infections, including 20 abscesses, 1 case of cerebritis,
      2 cases of fungus cerebri, and 82 cases of meningitis. gram-negative organisms,
      especially Klebsiella pneumoniae, were the most frequent offending organisms.
      Forty-one percent of the 133 deaths were due to infections, but the death rate
      from infection was only 4.4%. Univariate analysis showed mode of injury, number
      of lobes involved, ventricular penetration, paranasal sinus involvement, CSF
      fistulas, place of exploration, GCS score, and retained bone fragments to have
      significant bearing on the incidence of central nervous system infections. On the
      other hand, multivariate regression analysis disclosed the following factors each
      enhancing infection: CSF fistulas (chi2 = 46.526), transventricular injuries
      (chi2 = 13.4790), and paranasal petrous sinuses involvement (chi2 = 4.2221). When
      compared with primary exploration at the Nemazee Hospital, both exploration at a
      base hospital and no exploration at all were associated with increased chances of
      infection (chi2 = 4.7629 and 8.3220, respectively). Additionally, when
      tangential, crossed penetrating, and uncrossed penetrating injuries were compared
      with through-and-through injuries, the uncrossed penetrating mode was associated
      with less infection (chi2 = 0.1652, 2.6353, and 5.0817, respectively). Only two
      patients were readmitted for new evidence of infection 3 and 5 months after
      missile head wounds, one definitely due to and the other on suspicion of CSF
      fistulas. One hundred and thirty-seven of 587 patients with retained bone
      fragments were followed a mean of 42 months with no evidence of delayed
      infection. CONCLUSION: In this study, CSF fistulas and transventricular and
      paranasal sinus injuries all were associated with increased chances of central
      nervous system infections after military missile head wounds. Infection rate was
      lower in penetrating injuries not crossing into another dural compartment.
      Exploration at the Nemazee Hospital, despite delays in evacuation, had less
      incidence of infection than surgery at a base hospital within the first 24 hours
      of injury. Retained bone and metal fragments, a lower GCS score at the time of
      admission, secondary exploration at the Nemazee Hospital, and number of lobes
      involved were less important when evaluated in a multivariate regression model.

PMID- 9526985
TI  - Balloon angioplasty for the treatment of vasospasm: results of first 50 cases.
AB  - OBJECTIVE: To report the results of the first 50 consecutive patients with
      vasospasm secondary to subarachnoid hemorrhage treated with balloon angioplasty
      after failure of medical management. METHODS: Retrospective uncontrolled study of
      50 consecutive patients treated with balloon angioplasty between February 1988
      and July 1992. Forty-six had objective clinical deterioration despite maximal
      medical therapy, whereas four were treated on the basis of rapidly accelerating
      transcranial Doppler velocities and decreased regional blood perfusion detected
      by technetium-99m-exametazime brain single photon emission computed tomography.
      All patients had evidence of marked vasospasm demonstrated by angiography. Thirty
      two (64%) and 46 (92%) patients underwent angioplasty within 12 and 18 hours,
      respectively. RESULTS: Of the patients with clinical evidence of vasospasm
      induced ischemia, 28 (61%) showed sustained neurological improvement within 72
      hours of angioplasty. Three (6%) patients deteriorated within 72 hours after
      angioplasty, with two (4%) patients dying immediately after angioplasty as a
      result of vessel rupture and the other patient's Glasgow Coma Scale score
      decreasing by 2. Two additional patients in poor condition with Hunt and Hess
      Grade V at the time of angioplasty subsequently died during hospitalization. Two
      other patients died as a result of unclipped aneurysms that subsequently bled 4
      and 12 days after angioplasty, respectively. The improvement demonstrated
      clinically, angiographically, and by transcranial Doppler after angioplasty was
      sustained, with only one patient requiring subsequent angioplasty of a previously
      dilated segment (total, 170 vessel segments dilated). Two patients developed
      vasospasm in previously undilated segments. CONCLUSION: Timely balloon
      angioplasty can reverse delayed ischemic deficit caused by vasospasm in patients
      for whom medical therapy has failed.

PMID- 9526986
TI  - Intraoperative detection of malignant gliomas by 5-aminolevulinic acid-induced
      porphyrin fluorescence.
AB  - OBJECTIVE: Survival after surgery and radiotherapy for the treatment of malignant
      gliomas is linked to the completeness of tumor removal. Therefore, methods that
      permit intraoperative identification of residual tumor tissue may be of benefit.
      In a preliminary investigation, we have studied the value of fluorescent
      porphyrins that accumulate in malignant tissue after administration of a
      precursor (5-aminolevulinic acid) for labeling of malignant gliomas in nine
      patients. METHODS: Three hours before the induction of anesthesia, 10 mg 5
      aminolevulinic acid/kg body weight was administered orally. Intraoperatively, red
      porphyrin fluorescence was observed with a 455-nm long-pass filter after
      excitation with violet-blue (375-440 nm) xenon light and was verified by analysis
      of fluorescence spectra. Fluorescing and nonfluorescing samples taken from the
      tumor perimeters were examined histologically or used to study the photobleaching
      of porphyrins by excitation light and white light from the operating microscope.
      Plasma and erythrocyte porphyrin levels were determined by fluorescence
      photometry. RESULTS: Normal brain tissue revealed no porphyrin fluorescence,
      whereas tumor tissue was distinguished by bright red fluorescence. For a total of
      89 tissue biopsies, sensitivity was 85% and specificity was 100% for the
      detection of malignant tissue. For seven of nine patients, visible porphyrin
      fluorescence led to further resection of the tumor. Under operating light
      conditions, fluorescence decayed to 36% in 25 minutes for violet-blue light and
      in 87 minutes for white light. Plasma and erythrocyte porphyrin contents
      increased slightly, without exceeding normal levels. CONCLUSION: Our observations
      suggest that 5-aminolevulinic acid-induced porphyrin fluorescence may label
      malignant gliomas safely and accurately enough to enhance the completeness of
      tumor removal.

PMID- 9526987
TI  - Electrophysiological considerations regarding electrical stimulation of motor
      cortex and brain stem in humans.
AB  - OBJECTIVE: To provide information about activation of descending motor pathways
      in humans, motor evoked potentials were obtained from 16 patients without any
      sensorimotor deficit, after both cortical and brain stem stimulation. METHOD:
      Total anesthesia was achieved in all patients through intravenous administration.
      Short trains of one to five electrical pulses were delivered separately to the
      motor cortex and the brain stem. Compound muscle action potentials were recorded
      from the contralateral upper extremity. Threshold intensity, stimulus polarity,
      latencies, and effect of increased stimulus intensity on latencies were analyzed.
      RESULTS: The threshold intensity was significantly lower when stimulating the
      brain stem than when stimulating the cortex. A monophasic anodal stimulus was
      better for cortical stimulation than for brain stem stimulation. Conversely, a
      monophasic cathodal stimulus was more effective for brain stem stimulation. The
      rate of unsuccessful stimulations was higher with brain stem stimulation and with
      increased stimulation intensity. The variability of latencies was so high that a
      calculation of the conduction velocity of the motor pathways was not possible.
      CONCLUSION: The results indicate that cortical surface and brain stem stimulation
      act on different nervous elements. Because of the condensation of motor pathway
      fibers at the brain stem level, much less stimulus intensity for eliciting
      compound muscle action potentials was necessary. On the other hand, the higher
      rate of unsuccessful brain stem stimulations may be caused by a block of
      conduction at either the anterior horn cell pool or the neuromuscular junction.
      Thus, for cortical and for brain stem stimulation, different stimulating
      parameters seemed to be necessary with the patient under general anesthesia.

PMID- 9526988
TI  - Accuracy of continuous jugular bulb oximetry in the intensive care unit.
AB  - OBJECTIVE: To address the accuracy of a bedside jugular bulb oxygen saturation
      (SjO2) catheter monitor (Baxter-Edwards, Santa Ana, CA) versus in vitro co
      oximetry measurements in the intensive care unit (ICU). METHODS: By prospective
      protocol, we compared blood gas measurements with simultaneously recorded
      continuous bedside oximetric monitor values for 31 ICU patients with traumatic
      brain injury undergoing jugular bulb catheter monitoring. For suboptimal
      fiberoptic light signal quality indices, the catheter was repositioned, flushed,
      or both before drawing the sample for in vitro measurement. Laboratory and
      bedside monitor data were examined for association using the chi2 and paired t
      tests and a linear regression model. RESULTS: We assessed 195 samples (median, 5
      per patient; range, 1-14) who were monitored an average of 3.4 (range, 1-6) days.
      The in vivo monitor (range, 32-94%) and in vitro co-oximetry (range, 38-93%)
      values had acceptable correlation (y = 0.94x + 4.4, r2 = 0.80). For bedside
      monitor detection of jugular bulb desaturation (SjO2 < 50% for 10 min), the kappa
      statistic was 0.35, the sensitivity was 45 to 50%, and the specificity was 98 to
      100%. CONCLUSION: Continuous ICU SjO2 monitoring correlates significantly with in
      vitro values, but less so than previously described during intracranial surgery.
      Although sensitivity of the bedside monitor to detect confirmed desaturations
      remains an issue, the high specificity indicates that it is less of a concern
      that patients may be misdiagnosed as having desaturations resulting in
      unnecessary interventions. Nonetheless, suspected jugular bulb desaturation
      should be verified before taking therapeutic actions.

PMID- 9526990
TI  - Carotid arteriotomy closure using a vascular clip system.
AB  - PURPOSE: To compare a newly released vascular clip system (Vascular Clip-applier
      System; Auto Suture Company, Norwalk, CT) designed for sutureless vessel closures
      and anastomoses with standard suture closure of carotid arteriotomies after
      carotid endarterectomies. PATIENTS AND METHODS: Sixteen consecutive patients with
      symptomatic and severe carotid stenoses were randomly allocated to receive either
      standard suture (running 6-0 monofilament) or clip artery closures after
      undergoing carotid endarterectomies. The speed of arteriotomy closure was
      calculated for each procedure, and hemostasis, complications, and postoperative
      carotid patency were determined and recorded for each patient. RESULTS: The clip
      applier system performed well, and arteriotomy closure with clips was
      significantly faster than suture closure (0.36 cm/min in the sutured group versus
      0.52 cm/min in the clipped group, P = 0.019). Carotid patency assessed by
      ultrasonography 4 to 8 weeks after surgery showed that all arteries in both
      groups were patent. Two hemostasis problems occurred in the clip closure group,
      one minor that was caused by the use of incorrect clip size and one major that
      was probably caused by a combination of sudden arterial hypertension and clip
      failure. This complication resulted in a large neck hematoma and cross-clamp
      ischemia during the ensuing suture repair of the arterial dehiscence.
      CONCLUSIONS: As a result of this small study, we determined that clip closure of
      carotid arteriotomies was feasible, but it remains questionable whether the
      increased speed of a sutureless closure is clinically important for this
      procedure. Concerns regarding the strength of clip closure of an
      endarterectomized vessel and the cost of clip closure compared with standard
      suture techniques suggest that there may be no clinically significant benefits of
      arterial clip closure over suture closure after carotid endarterectomy, and there
      is potentially some risk.

PMID- 9526991
TI  - Apoptosis in neurological disease.
AB  - Enormous interest in cell death in the past several years has moved apoptosis to
      the forefront of scientific research. Apoptosis has been found to mediate cell
      deletion in tissue homeostasis, embryological development, and immunological
      functioning. It also occurs in pathological conditions, including cancer and
      acquired immunodeficiency syndrome, and is implicated in neurodegenerative
      diseases. Claims of neuronal apoptosis induced by various agents and conditions
      are published regularly, but in many instances the data are questionable because
      they are incomplete. This review presents a brief history of apoptosis and
      describes the evidence required before claims of apoptosis are made. Summaries
      and critiques of important investigations concerning the genetic and biochemical
      regulation of neuronal apoptosis are presented, as are other studies describing
      connections between apoptosis and neuronal cell death in physiological and
      pathological situations. There is a realization that apoptosis can be programmed
      and is distinguishable from necrotic cell death. Combining apoptosis with
      programmed cell death produces misleading terminology and confusion over these
      two forms of cell degeneration. Further investigations into neuronal apoptosis
      should focus on all of the criteria that the original investigators outlined 25
      years ago, to clarify whether apoptosis and/or another form of cell death
      mediates neuronal degeneration in physiological settings and in neurological
      diseases such as Alzheimer's disease, Parkinson's disease, epilepsy, and
      ischemia/stroke.

PMID- 9526989
TI  - Clinical evaluation of paresthesia steering with a new system for spinal cord
      stimulation.
AB  - OBJECTIVE: The goal was to evaluate, in a clinical study, the predicted
      performance of the transverse tripolar system for spinal cord stimulation,
      particularly the steering of paresthesia, paresthesia coverage, and the
      therapeutic range of stimulation. METHODS: Six transverse tripolar electrodes
      were implanted in the lower thoracic region in four patients experiencing chronic
      neuropathic pain. Electrode positions, relative to the spinal cord, were
      estimated from computed tomographic scans. A dual-channel stimulator was used for
      initial percutaneous tests, and an implanted single-channel stimulator was used
      for follow-up test sessions. Nine "balance" settings and several cathode-anode
      combinations were used with the dual-channel and single-channel stimulator,
      respectively. In each test, the increase of paresthesia coverage from the
      perception threshold to the discomfort threshold was registered on a body map and
      the corresponding voltages were recorded. RESULTS: Paresthesia steering occurred
      in all but one patient. The normalized steering score, enabling quantitative
      comparisons of paresthesia steering among tests and patients, showed that maximum
      paresthesia steering occurred when the electrode was at least 3 mm dorsal to the
      spinal cord and centered <2 mm from its midline. Paresthesia coverage included 70
      to 100% of the body up to the electrode level, unless the electrode migrated or
      had broken wires. The therapeutic range, defined as the discomfort/perception of
      paresthesia threshold ratio, varied from 1.6 to 4.0. CONCLUSION: The clinical
      performance of transverse tripolar stimulation is in accordance with the
      characteristics predicted by computer modeling. It enables finer control of
      paresthesia than that achieved by polarity changes in conventional spinal cord
      stimulation systems.

PMID- 9526992
TI  - Evolution of neuroablative surgery for involuntary movement disorders: an
      historical review.
AB  - Surgical therapy of involuntary movement disorders has evolved during the past
      century from gross destructive ablations of the central nervous system to
      refined, accurate, discrete lesioning of sites deep within the brain. The
      understanding of neuroanatomic and physiological systems improved tremendously
      through experimentation in animals and empirical observations of surgery in
      humans. A continuum of accumulated knowledge has been achieved through ablation
      or lesioning of virtually all aspects of the central and peripheral nervous
      system predicated on previous successes or failures. This compilation of surgical
      history of involuntary movement disorders has provided present neurosurgeons with
      the foundations on which they base their therapeutic measures and will direct
      future endeavors within this field.

PMID- 9526993
TI  - The use of lipid-coated microbubbles as a delivery agent of 7beta
      hydroxycholesterol in a radiofrequency lesion in the rat brain.
AB  - OBJECTIVE: This laboratory has previously described the aggregation of
      intravenously administered lipid-coated microbubbles (LCM) around tumors and
      areas of injury. 7Beta-hydroxycholesterol has been used to inhibit astrocytic
      proliferation in nervous system injury models. The compound has been given by
      direct infusion, by epidural catheter, or in liposomes (delivered
      stereotactically to the injury site). In this article, we report the use of LCM
      to deliver 7beta-hydroxycholesterol to a radiofrequency injury site in the rat
      cerebrum. METHODS: First, the ability of LCM to target the thermal lesion in the
      rat brain was characterized using a lipid-soluble fluorescent dye 3,3
      dioctadecyloxacarbocyanine perchlorate. Then, the effectiveness of this delivery
      system in suppression of glial proliferation was measured by glial fibrillary
      acidic protein immunoreactivity. RESULTS: Glial fibrillary acidic protein
      immunoreactivity was significantly reduced when 7beta-hydroxycholesterol was
      administered via LCM but not alone, suggesting that astrocytic proliferation
      would correspondingly be diminished. CONCLUSION: LCM were assessed as a delivery
      vehicle for 7beta-hydroxycholesterol in a rat brain radiofrequency lesion and
      found to be efficient in reducing astrogliosis, as measured by glial fibrillary
      acidic protein immunoreactivity.

PMID- 9526994
TI  - Role of extracellular matrix in tumor invasion: migration of glioma cells along
      fibronectin-positive mesenchymal cell processes.
AB  - OBJECTIVE: The major morbidity of glioma lies in its infiltrative growth. One of
      the major patterns of this invasive growth is the formation of Scherer's
      secondary structures associated with the blood vessels and the leptomeninges. To
      better understand the role of extracellular matrix (ECM) in glioma invasion, we
      investigated in vitro the interaction between glioma cells and the meningeal
      mesenchymal tissue from the brain. As an aid to this study, ECM in glioma cell
      line spheroids was compared with that in primary fetal brain aggregates. METHODS:
      To study the expression of ECM, four glioma cell lines (U-87 MG, U-251 MG,
      AN1/lac-z, and HF-66) and primary cells from fetal rat brain were grown as
      spheroids and monolayers. To sudy the role of ECM in glioma invasion, spheroids
      from the glioma cell lines were grown over established cultures of fetal
      meningeal and mesenchymal tissue. Expression of fibronectin, laminin, tenascin,
      collagen VI, and chondroitin sulfate proteoglycan was studied by
      immunofluorescence. RESULTS: Expression of ECM by the spheroids was variable. U
      87 MG expressed most of the ECM components robustly, whereas AN1/lac-z expressed
      them all weakly. Fetal rat brain aggregates produced minimal ECM. In cocultures
      of glioma spheroids and fetal meningeal mesenchymal tissue, individual cells from
      the glioma spheroids that expressed least fibronectin (AN1/lac-z and U-251 MG)
      migrated along the fibronectin-positive mesenchymal cells in the culture dish.
      Cells from the other two lines (U-87 MG and HF-66) that expressed fibronectin
      strongly did not demonstrate such behavior. None of the other ECM components
      showed a similar association; mesenchymal cells did not express laminin as
      strongly as fibronectin, and glioma cells were not observed to align with the
      laminin-positive structures. CONCLUSION: This study suggests that fibronectin may
      play a key role in intracerebral invasion of glioma cells.

PMID- 9526995
TI  - The hydroxyurea-induced loss of double-minute chromosomes containing amplified
      epidermal growth factor receptor genes reduces the tumorigenicity and growth of
      human glioblastoma multiforme.
AB  - OBJECTIVE: We investigated whether the hydroxyurea-induced loss of double-minute
      chromosomes containing amplified epidermal growth factor receptor (EGFR) genes
      would lead to a loss of tumorigenicity of a glioblastoma multiforme cell line.
      METHODS: Glioblastoma multiforme cells were treated in vitro with 0 (HU0) or 100
      micromol/L (HU100) hydroxyurea and then injected into the flanks of nude mice.
      Survival and tumor volumes were evaluated. Pulsed-field gel electrophoresis,
      Southern blot hybridization, and slot-blot analysis were used to determine EGFR
      amplification levels. Flow cytometry and immunofluorescent staining were used for
      cell-cycle analysis and EGFR protein expression. RESULTS: Prior to injection,
      HU100 cells lost 95% of their amplified EGFR genes and developed into tumors 6
      weeks after injection versus 3 weeks for HU0 cells. Mice with HU100 tumors had a
      median survival of 62 days versus 43 days for control mice with HU0 tumors. Pulse
      field gel electrophoresis analysis showed that HU100 tumors had reamplified the
      EGFR gene as double-minute chromosomes of the same size as those originally
      present before hydroxyurea treatment. When HU100 cells were cultured in the
      absence of hydroxyurea, the EGFR gene also reamplified. HU100 cells grew at less
      than half the rate of untreated HU0 control cells in culture and showed a
      decreased number of cells entering the cell cycle. Immunofluorescent staining of
      HU150 (150 micromol/L) cells showed decreased EGFR protein expression.
      CONCLUSION: The EGFR gene is important for tumorigenicity in mice and growth in
      culture. Hydroxyurea induces the loss of double-minute chromosome-amplified EGFR
      genes against a selection gradient and significantly delays the onset of tumors.
      These results support the potential use of low-dose hydroxyurea for the treatment
      of human glioblastoma multiforme.

PMID- 9526996
TI  - Induced hypertension improves regional blood flow and protects against infarction
      during focal ischemia: time course of changes in blood flow measured by laser
      Doppler imaging.
AB  - OBJECTIVE: To characterize changes in regional blood flow (rCBF) during and after
      a period of arterial occlusion and determine the effect on rCBF and on the extent
      of infarction when the mean arterial blood pressure is increased during the
      period of occlusion. METHODS: rCBF in the middle cerebral artery (MCA) territory
      of rabbits was monitored using laser Doppler perfusion imaging before, during,
      and after a 1- or 2-hour period of MCA occlusion, and the size of the infarction
      was assessed by 2,3,5-triphenyltetrazolamine chloride staining after 2 hours of
      reperfusion. Test animals, the mean arterial blood pressure of which was
      increased by 65 mm Hg with intravenous phenylephrine during the ischemia, were
      compared with control animals that remained normotensive. The laser Doppler
      perfusion imager (Lisca Developments Co., Linkoping, Sweden) scanned a 3-cm2 area
      of cortex with a resolution of 4 mm2 every 15 minutes. RESULTS: MCA occlusion
      reduced rCBF to 71 +/- 2% of the control level (n = 24, P < 0.001). Hypertension
      (HTN) restored rCBF to 84 +/- 3% of the control level (n = 12, P < 0.01), but the
      HTN-induced improvement diminished with time, so that after 1 hour, there was no
      longer a significant difference between hypertensive and normotensive animals.
      HTN during the MCA occlusion caused a 97% reduction in infarct size (P < 0.05) in
      the animals subjected to 1 hour of occlusion but caused only a 45% reduction (P
      approximately 0.1) in the animals subjected to 2 hours of occlusion. CONCLUSION:
      This study supports the use of HTN to minimize ischemic injury from short
      intervals of major intracranial vessel occlusion but fails to demonstrate
      protection when HTN is maintained during occlusions of more than 1 hour.

PMID- 9526997
TI  - Spinal cord blood flow and pathophysiological changes after transient spinal cord
      ischemia in cats.
AB  - OBJECTIVE: The goal was to study the hemodynamics and regional pathophysiological
      changes in the spinal cord after transient vascular occlusion in cats. METHODS:
      We measured spinal cord blood flow (SCBF) continuously in the lumbar region with
      a laser-doppler flowmeter, before, during, and after spinal cord ischemia induced
      by balloon occlusion of the thoracic aorta, in 24 cats (divided into three
      groups) and simultaneously recorded the evoked spinal cord potentials (ESPs). In
      each group (n = 8), 10-, 20-, and 30-minute ischemic loading was performed. All
      animals were evaluated neurologically 36 hours later, and then their spinal cords
      were examined histologically. RESULTS: The amplitude of ESPs decreased 10 minutes
      and disappeared 20 minutes after occlusion. SCBF increased to as much as 2 times
      the control values after reperfusion and decreased gradually in all groups. Then,
      in all animals in the 10-minute group and six animals in the 20-minute group,
      SCBF returned to the control values, which were subsequently maintained
      throughout the experiment, and ESPs returned to normal patterns within 1 hour.
      For all animals in the 30-minute group and two in the 20-minute group,
      hypoperfusion after recirculation, irreversible amplitude changes in ESPs,
      postischemic paraparesis, and pathological ischemic changes in the lower thoracic
      and lumbar spinal segments were recognized. CONCLUSION: Our results showed that >
      20-minute occlusion of the thoracic aorta in cats resulted in irreversible spinal
      perfusion disorders and that the monitoring of SCBF and ESPs could be useful for
      predicting potential neurological deficits. Furthermore, postischemic
      hypoperfusion may have an important role in the development of secondary spinal
      cord ischemia, resulting in severe neurological dysfunction. This observation
      suggested the possibility of therapeutic modification of the secondary processes
      inducing hypoperfusion after spinal ischemia.

PMID- 9526998
TI  - Parafalcine and bilateral convexity neurosarcoidosis mimicking meningioma: case
      report and review of the literature.
AB  - OBJECTIVE AND IMPORTANCE: Sarcoidosis is a granulomatous disorder of unknown
      origin that may rarely present solely as an intracranial tumor. Neurosarcoidosis
      can mimic more common disease processes, such as meningioma, glioma, or
      metastases. It is important to keep neurosarcoidosis in mind, both preoperatively
      and intraoperatively, to guide appropriate treatment. We present a case of
      neurosarcoidosis mimicking a parafalcine and bilateral convexity meningioma.
      CLINICAL PRESENTATION: A 44-year-old African-American woman was referred to our
      institution with a diagnosis of meningioma based on a 4-month history of
      headaches, decreased memory, personality changes, and decreased coordination and
      on the results of axial computed tomography, which revealed a parafalcine and
      bilateral convexity mass. INTERVENTION: Cerebral arteriography and magnetic
      resonance imaging were performed to better characterize the lesion for
      anticipated surgery. Despite corticosteroid therapy, the patient continued to
      have progressive symptoms and underwent surgery. Intraoperative frozen sections
      were consistent with neurosarcoidosis. The mass was then significantly debulked
      unilaterally. CONCLUSION: Laboratory studies and follow-up examinations revealed
      no evidence of systemic sarcoidosis. The patient received corticosteroid therapy
      and subsequently improved. Serial magnetic resonance imaging examinations during
      several months revealed decreasing tumor size.

PMID- 9526999
TI  - Lipomatous glioneurocytoma of the posterior fossa with divergent differentiation:
      case report.
AB  - OBJECTIVE AND IMPORTANCE: We report a case of a posterior fossa neuroepithelial
      tumor with unusual clinical presentation, magnetic resonance imaging appearance,
      and morphological features. CLINICAL PRESENTATION: This 66-year-old man presented
      with a history of gait ataxia, dizziness, and tinnitus and was found to have a
      large tumor in the posterior fossa and cerebellopontine angle. INTERVENTION:
      Gross total excision of the tumor was accomplished. Histologically, the most
      unique features were macrovesicular accumulations of lipid, giving the tumor (at
      least focally) an appearance virtually identical to that of mature adipose
      tissue. Evidence of biphasic neuronal and glial differentiation was noted by
      immunohistochemistry and electron microscopy. CONCLUSION: A literature review is
      presented. Diagnostically, this neoplasm seems to fit in a unique group of rarely
      described, lipomatous neuroectodermal tumors that show divergent neuronal and
      glial differentiation.

PMID- 9527000
TI  - Treatment of rhinocerebral mucormycosis with intravenous interstitial, and
      cerebrospinal fluid administration of amphotericin B: case report.
AB  - IMPORTANCE: Rhinocerebral mucormycosis is extremely difficult to treat.
      Approximately 70% of patients are poorly controlled diabetics, and many of the
      remainder are immunocompromised as a consequence of cytotoxic drugs, burn
      injuries, or end-stage renal disease. Despite standard treatment consisting of
      surgical debridement and the intravenous administration of amphotericin B,
      rhinocerebral mucormycosis is usually a fatal disease. CLINICAL PRESENTATION: We
      describe the case of a 16-year-old male patient with juvenile onset diabetes
      mellitus who presented with fever, right-sided hemiparesis, and dysarthria. Axial
      view computed tomography revealed abscess formation in the left basal ganglia and
      frontal lobe, which was proven by stereotactic biopsy to contain Rhizopus oryzae.
      INTERVENTION: Intravenous administration of amphotericin B (30-280 mg/dose) was
      begun on the day of admission. On hospital Day 20, after the occurrence of frank
      abscess formation, the lesion was aggressively debrided. Despite these therapies,
      there was neurological deterioration characterized by the development of
      hemiplegia and aphasia. Sequential computed tomographic scans enhanced with
      contrast medium demonstrated progressively enlarging lesions. Ommaya reservoirs
      were placed into the abscess cavity and the frontal horn of the contralateral
      lateral ventricle. The patient was then treated with intracavitary/interstitial
      injections of amphotericin B during the course of 80 days and three doses of
      intraventricular amphotericin B. Clinical and radiographic improvement was
      achieved after treatment. Two years after the initial diagnosis, magnetic
      resonance imaging of the brain showed no evidence of disease and an examination
      revealed a neurologically intact and fully functional patient. CONCLUSION: We
      conclude that with an infection as morbid as rhinocerebral mucormycosis, it is
      advisable to use surgical debridement and all available routes for delivering
      amphotericin B to infected cerebral parenchyma, which include intravenous,
      intracavitary/interstitial, and cerebrospinal fluid perfusion pathways.

PMID- 9527001
TI  - A composite silent corticotroph pituitary adenoma with interspersed
      adrenocortical cells: case report.
AB  - OBJECTIVE AND IMPORTANCE: A case report of an extraordinary sellar pituitary
      tumor composed of corticotrophs and adrenocortical cells is presented. To our
      knowledge, this is only the second one reported in the literature. CLINICAL
      PRESENTATION: An 18-year-old female patient presented with amenorrhea.
      INTERVENTION: Investigations revealed a sellar mass, which was excised
      transsphenoidally. Histologically, two cell types could be readily distinguished,
      i.e., small basophilic cells that were positive for periodic acid Schiff and
      adrenocorticotropic hormone and large cells with abundant, slightly vacuolated,
      eosinophilic cytoplasm that were negative for periodic acid Schiff and
      adrenocorticotropic hormone. The nature of the tumor was revealed by
      ultrastructural examination, thus highlighting the importance of this technique
      in the investigation of pituitary adenomas. Immunohistochemistry with a panel of
      steroidogenic dehydrogenases and hydroxylases was positive in the large cells,
      confirming these as adrenocortical cells. CONCLUSION: We suggest that the
      designation "composite silent corticotroph pituitary adenoma with adrenocortical
      cells" is an appropriate name for this tumor. The explanation for the presence of
      the two cell types is obscure. Two theories are considered, as were proposed by
      the authors of the previous case report regarding the same entity, i.e., 1) the
      possibility of misplaced embryonic adrenocortical cells and 2) the presence of
      uncommitted stem cells that differentiate into adrenocortical cells.

PMID- 9527002
TI  - Neurenteric cyst of the cerebellopontine angle: case report.
AB  - OBJECTIVE AND IMPORTANCE: We report a case of a neurenteric cyst of the
      cerebellopontine angle and review the five previously reported cases. The
      pathology and classification of these cysts are discussed. CLINICAL PRESENTATION:
      The patient presented with a 1-month history of nausea, vomiting, vertigo, and
      sudden hearing loss. INTERVENTION: The cyst was decompressed by a retrosigmoid
      approach. After recurrence of symptoms at 2 months, further decompression was
      required. CONCLUSION: The patient achieved a good outcome after the second
      operation, with cessation of her vomiting and vertigo, although she had residual
      hearing loss. Four of the five previously reported patients experienced
      satisfactory outcomes after surgery. The definitive diagnosis of these rare
      lesions is made using immunocytochemical techniques.

PMID- 9527003
TI  - Secondary hemorrhage after intraventricular fibrinolysis: a cautionary note: a
      report of two cases.
AB  - OBJECTIVE AND IMPORTANCE: To hasten the lysis of intraventricular hemorrhages,
      intraventricular administration of recombinant tissue plasminogen activator (rt
      PA) or urokinase has been advocated as an effective and safe treatment for
      patients with intraventricular hemorrhage. Until now, cases of secondary
      hemorrhage after intraventricular fibrinolysis, to our knowledge, have not been
      reported in the literature. We present a report of two patients with clinically
      significant bleeding complications associated with intraventricular infusion of
      rt-PA. CLINICAL PRESENTATION: Both patients, a 42-year-old woman (Patient 1) and
      a 70-year-old man (Patient 2), suffered from hypertensive left-sided thalamic
      hemorrhage with ventricular extension and ventricular dilatation. INTERVENTION:
      Both patients required external ventricular drainage and were treated with
      intraventricular rt-PA. In Patient 1, a secondary intraventricular hemorrhage
      occurred 20 minutes after the first instillation of 2 mg of rt-PA and was
      associated with a sudden loss of consciousness. Treatment with rt-PA was stopped,
      and the patient needed a permanent shunt. In Patient 2, intraventricular
      subsequent bleeding was noted 4 hours after the second 4-mg dose of rt-PA,
      clinically apparent as anisocoria. In Patient 2, rt-PA administration was
      continued without further complications. In both patients, a second external
      ventricular drainage was required after secondary hemorrhage. CONCLUSION:
      Intraventricular lysis is a potentially hazardous therapy. To weigh the potential
      benefits against the potential risks, a controlled study of this promising new
      treatment is urgently warranted.

PMID- 9527004
TI  - Saccular aneurysms of meningeal artery: case report.
AB  - OBJECTIVE AND IMPORTANCE: A rare observation of double saccular aneurysms of the
      meningeal artery is presented. CLINICAL PRESENTATION: This 22-year-old man was
      referred to the Neurosurgical Institute with a suspicion of an aneurysm of the
      anterior communicating artery. Bilateral angiography of the carotid arteries was
      performed 1 week after the subarachnoid hemorrhage, but the aneurysms were not
      visualized. Routine angiography of both carotid arteries and selective studies of
      the left vertebral artery were performed again, and angiography of the right
      carotid artery revealed an aneurysm. The patient's neurological state at the time
      of admission was normal. Fundoscopic examination revealed papilledema and
      conjunctival injection of the left eye. INTERVENTION: The patient was treated
      using a right pterional approach. One aneurysm had caused spontaneous
      subarachnoid hemorrhage. The aneurysms were removed using a direct approach, with
      histological examination of dura matter fragment containing both aneurysms. The
      results of the patient's 2-week follow-up examination were normal. Follow-up
      angiography of the right carotid artery showed absence of the aneurysm with a
      clip on the branch of meningeal artery. CONCLUSION: Saccular aneurysms of the
      meningeal artery can be manifested by subarachnoid hemorrhage, and intradural
      arterial aneurysms are similar to saccular cerebral vessel lesions structurally.

PMID- 9527005
TI  - Saphenous vein graft reconstruction of an unclippable giant basilar artery
      aneurysm performed with the patient under deep hypothermic circulatory arrest:
      technical case report.
AB  - OBJECTIVE AND IMPORTANCE: Effective treatment for unclippable giant
      vertebrobasilar aneurysms remains unclear. We present the first reported case of
      a giant vertebrobasilar aneurysm being successfully treated with trapping of the
      aneurysm and internal carotid artery to basilar artery bypass with a saphenous
      vein graft that was performed with the patient under hypothermic circulatory
      arrest. CLINICAL PRESENTATION: A 15-year-old female patient with a history of
      probable subarachnoid hemorrhage and chronic headaches presented with a
      relatively acute exacerbation of her headache, nausea, vomiting, and weakness.
      Imaging studies revealed a 4 x 4 x 3-cm vertebrobasilar aneurysm, supplied by an
      angiographically dominant right vertebral artery and causing significant brain
      stem compression. INTERVENTION: Initially, a petrosal approach with a hearing
      preserving partial labyrinthectomy was used to perform a right external carotid
      artery to posterior cerebral artery bypass with saphenous vein. Delayed occlusion
      of the right vertebral artery with an intraluminal balloon was planned; however,
      intraoperative angiography revealed poor graft flow, presumably because of the
      small size of the posterior cerebral artery. Postoperative graft occlusion was
      anticipated. During this same time interval, the patient deteriorated
      neurologically. Brain imaging failed to reveal evidence of cerebral infarction.
      The patient underwent subsequent surgery. After a total petrosectomy, the
      aneurysm was trapped, an aneurysmectomy was performed, and, with the patient
      under deep hypothermic circulatory arrest, a new interposition saphenous vein
      graft was inserted between the internal carotid and basilar arteries. Excellent
      flow was observed angiographically. At her 4-month follow-up examination, the
      patient had improved to near baseline. CONCLUSION: We present a technically
      challenging but safe and definitive treatment option for an unclippable giant
      vertebrobasilar aneurysm. Using cranial base approaches and hypothermic
      circulatory arrest techniques, aneurysmal trapping and successful bypass grafting
      directly into the basilar artery was performed.

PMID- 9527006
TI  - Expanding cava septi pellucidi and cava vergae in children: report of three
      cases.

PMID- 9527007
TI  - Surgical and neurological complications in a series of 708 epilepsy surgical
      procedures.

PMID- 9527008
TI  - Routine angiography after surgery for ruptured intracranial aneurysms: a cost
      versus benefit analysis.

PMID- 9527009
TI  - Pineal region tumors and the role of stereotactic biopsy: review of the
      mortality, morbidity, and diagnostic rates in 370 cases.

PMID- 9527010
TI  - Isolation and long-term survival of adult human sensory neurons in vitro.
AB  - OBJECTIVE: To determine whether adult human dorsal root ganglion neurons can be
      isolated and maintained in long-term tissue culture, where they would extend
      processes. METHODS: Dorsal root ganglia were removed from adult human organ
      donors within 2 hours of clamping the aorta. They were then treated with enzymes
      for one hour, triturated to dissociate the neurons and their satellite cells, and
      the individual neurons were then plated in tissue culture dishes in medium
      containing serum. RESULTS: Isolated adult human dorsal root ganglion neurons
      survive in vitro for more than 2 1/2 months, in the absence of exogenously
      supplied neurotrophins. where they remain electrically excitable and extend
      processes, CONCLUSIONS: Isolated adult human dorsal root ganglion neurons survive
      in culture for more than 2 1/2 months, extend processes, and remain electrically
      excitable, without exogenous neurotrophins. These results suggest that, adult
      human sensory neurons do not require exogenous neurotrophins for survival and
      process outgrowth, or that sufficient factors were provided by the small number
      of satellite cells in the cultures. In addition, the neurons survive well in
      spite of an initial period of up to 14 hours of hypoxia, between the time the
      aorta was clamped and when the plated neurons were placed in an incubator with
      the appropriate O2/CO2 environment.

PMID- 9527011
TI  - GABAergic deafferentation hypothesis of brain aging and Alzheimer's disease
      revisited.
AB  - Considering the mechanisms responsible for age- and Alzheimer's disease (AD)
      related neuronal degeneration, little attention was paid to the opposing
      relationships between the energy-rich phosphates, mainly the availability of the
      adenosine triphosphate (ATP), and the activity of the glutamic acid decarboxylase
      (GAD), the rate-limiting enzyme synthesizing the gamma-amino butyric acid (GABA).
      Here, it is postulated that in all neuronal phenotypes the declining ATP-mediated
      negative control of GABA synthesis gradually declines and results in age- and AD
      related increases of GABA synthesis. The Ca2+-independent carrier-mediated GABA
      release interferes with Ca2+-dependent exocytotic release of all transmitter
      modulators, because the interstitial (ambient) GABA acts on axonal preterminal
      and terminal varicosities endowed with depolarizing GABA(A)-benzodiazepine
      receptors; this makes GABA the "executor" of virtually all age- and AD-related
      neurodegenerative processes. Such a role of GABA is diametrically opposite to
      that in the perinatal phase, when the carrier-mediated GABA release, acting on
      GABA(A)/chloride ionophore receptors, positively controls chemotactic migration
      of neuronal precursor cells, has trophic actions and initiates synaptogenesis,
      thereby enabling retrograde axonal transport of target produced factors that
      trigger differentiation of neuronal phenotypes. However, with advancing age, and
      prematurely in AD, the declining mitochondrial ATP synthesis unleashes GABA
      synthesis, and its carrier-mediated release blocks Ca2+-dependent exocytotic
      release of all transmitter-modulators, leading to dystrophy of chronically
      depolarized axon terminals and block of retrograde transport of target-produced
      trophins, causing "starvation" and death of neuronal somata. The above scenario
      is consistent with the following observations: 1) a 10-month daily administration
      to aging rats of the GABA-chloride ionophore antagonist, pentylenetetrazol, or of
      the BDZ antagonist, flumazenil (FL), each forestalls the age-related decline in
      cognitive functions and losses of hippocampal neurons; 2) the brains of aging
      rats, relative to young animals, and the postmortem brains of AD patients,
      relative to age-matched controls, show up to two-fold increases in GABA
      synthesis; 3) the aging humans and those showing symptoms of AD, as well as the
      aging nonhuman primates and rodents--all show in the forebrain dystrophic axonal
      varicosities, losses of transmitter vesicles, and swollen mitochondria. These
      markers, currently regarded as the earliest signs of aging and AD, can be
      reproduced in vitro cell cultures by 1 microM GABA; the development of these
      markers can be prevented by substituting Cl- with SO4(2-); 4) the extrasynaptic
      GABA suppresses the membrane Na+, K+-ATPase and ion pumping, while the resulting
      depolarization of soma-dendrites relieves the "protective" voltage-dependent Mg2+
      control of the N-methyl-D-aspartate (NMDA) channels, thereby enabling Ca2+
      dependent persistent toxic actions of the excitatory amino acids (EAA); and 5) in
      whole-cell patch-clamp recording from neurons of aging rats, relative to young
      rats, the application of 3 microM GABA, causes twofold increases in the whole
      cell membrane Cl- conductances and a loss of the physiologically important
      neuronal ability to desensitize to repeated GABA applications. These age-related
      alterations in neuronal membrane functions are amplified by 150% in the presence
      of agonists of BDZ recognition sites located on GABA receptor. The GABA
      deafferentation hypothesis also accounts for the age- and AD-related degeneration
      in the forebrain ascending cholinergic, glutamatergic, and the ascending
      mesencephalic monoaminergic system, despite that the latter, to foster the
      distribution-utilization of locally produced trophins, evolved syncytium-like
      connectivities among neuronal somata, axon collaterals, and dendrites, to
      bidirectionally transport trophins. (ABSTRACT TRUNCATED)

PMID- 9527012
TI  - Binding profiles and physical dependence liabilities of selected benzodiazepine
      receptor ligands.
AB  - In vitro binding profiles were determined for selected benzodiazepine receptor
      (BZR) ligands by quantitative radioautography in rat brain. The ligands represent
      subtype-selective agonists (zolpidem) or nonselective BZR agonists (diazepam), as
      well as BZR partial agonists (bretazenil, Ro 43-9624, and Ro 19-8022). In
      addition, these compounds were evaluated in a precipitated withdrawal paradigm in
      monkeys. The physical dependence liability was not clearly related to the in
      vitro brain BZR binding profiles of these compounds. Therefore, diazepam,
      bretazenil, Ro 19-8022, and Ro 43-9624 had regional affinities for the 13
      selected rat brain regions that were close to the mean values across regions,
      despite the clearly greater physical dependence potential of diazepam. Zolpidem,
      on the other hand, had regional affinities for the 13 rat brain regions that
      diverged significantly from the mean value across regions and exhibited a lower
      physical dependence potential than diazepam. These results raise the possibility
      that a combination of BZR subtype selectivity with partial agonism could yield a
      marked reduction of physical dependence liability.

PMID- 9527013
TI  - The excitatory effects of the amygdala on hypothalamo-pituitary-adrenocortical
      responses are mediated by hypothalamic norepinephrine, serotonin, and CRF-41.
AB  - The hypothalamic neural mechanisms that are involved in the facilitatory effects
      of the amygdala (AMG) on the hypothalamo-pituitary-adrenocortical (HPA) axis have
      been investigated in rats. Stimulation of the central AMG nucleus caused a
      depletion of hypothalamic CRF-41, presumably due to its release into the portal
      circulation, and a subsequent rise in plasma ACTH and corticosterone (CS) levels.
      These effects were inhibited in rats in which hypothalamic norepinephrine (NE) or
      serotonin (5-HT) was depleted by catecholamine or serotonin neurotoxins,
      respectively. Furthermore, the administration of prazosin, an alpha1, but not of
      atenolol, which is a beta-blocker, as well as administration of the 5-HT2 blocker
      ketanserin inhibited the ACTH and CS responses to AMG stimulation. These results
      indicate that the facilitatory effects of the AMG on the HPA axis are mediated by
      hypothalamic NE via alpha1 receptors and by 5-HT via 5-HT2 receptors, as well as
      by CRF-41 in the paraventricular nucleus.

PMID- 9527014
TI  - Effects of central injection of kyotorphin and L-arginine on oxytocin and
      vasopressin release and blood pressure in conscious rats.
AB  - Intracerebroventricular (I.C.V.) administration of an inhibitor of nitric oxide
      synthase (NOS) increases oxytocin but not vasopressin secretion, in dehydrated
      rats [38]. Surprisingly, central injection of L-arginine, the substrate for NOS,
      caused a similar effect. Kyotorphin (L-tyrosyl-L-arginine), a dipeptide formed
      from L-arginine by kyotorphin synthetase in the brain may mediate this
      magnocellular response. Therefore, the dose and time responses of hormone release
      were compared following I.C.V. injection of kyotorphin and L-arginine to
      conscious rats that were normally hydrated or deprived of water for 24 h. In
      water-sated rats, both L-arginine and kyotorphin increased blood pressure and
      plasma glucose levels coincident with elevating circulating levels of oxytocin,
      but not vasopressin. In dehydrated animals, both L-arginine and kyotorphin
      increased plasma oxytocin levels with a similar time course but only kyotorphin
      decreased vasopressin release. D-arginine, like L-arginine, stimulated secretion
      of oxytocin, indicating a nonstereospecific effect. A kyotorphin receptor
      antagonist (L-leucyl-L-arginine) given I.C.V. to dehydrated animals elevated
      plasma oxytocin and prevented the decrease in vasopressin levels after
      kyotorphin. Thus, kyotorphin, but not L-arginine, appears to attenuate release of
      vasopressin either directly from magnocellular neurons or indirectly via
      modulating compensatory reflexes activated by the pressor response. On the other
      hand, an excess of L-arginine and kyotorphin within the CNS may mimic the stress
      response by augmenting release of oxytocin and activating the sympathetic nervous
      system to increase blood pressure and plasma glucose levels.

PMID- 9527015
TI  - Beta-amyloid-induced cholinergic denervation correlates with enhanced nitric
      oxide synthase activity in rat cerebral cortex: reversal by NMDA receptor
      blockade.
AB  - Ample experimental evidence indicates that acute beta-amyloid infusion into the
      nucleus basalis of rats elicits abrupt degeneration of the magnocellular
      cholinergic neurons projecting to the cerebral cortex. In fact, involvement of a
      permanent Ca2+ overload, partially via N-methyl-D-aspartate (NMDA) receptors, was
      proposed as a pivotal mechanism in beta-amyloid-induced neurodegeneration. A
      definite measure of NMDA receptor-mediated processes and subsequent Ca2+ entry is
      the induction of Ca2+/calmodulin-activated neuronal nitric oxide synthase (nNOS)
      in nerve cells. In the present account we therefore assessed activation of nNOS
      in correlation with cholinergic decline after beta-amyloid(1-42) or beta
      amyloid(25-35) infusion into the rat nucleus basalis. The results demonstrate the
      beta-amyloid conformation-dependent enhancement of cortical nitric oxide synthase
      (NOS) activity. Furthermore, chronic application of the polyamine site NMDA
      receptor blocker ifenprodil effectively attenuated beta-amyloid neurotoxicity. We
      propose that nNOS activation reflects the degree of beta-amyloid-induced
      excitotoxic injury in a proportional manner. Moreover, Ca2+-mediated processes
      via NMDA receptors, or direct binding of beta-amyloid to this receptor may be a
      critical step in the neurotoxic mechanisms in vivo.

PMID- 9527016
TI  - Complement depletion improves neurological function in cerebral ischemia.
AB  - The contribution of the complement system to the exacerbation of cerebral
      ischemia/reperfusion injury was studied by comparing a group of rats with normal
      complement levels to another group that was complement depleted by cobra venom
      factor (CVF). The magnitude of reactive hyperemia was significantly greater in
      the complement depleted animals. There was also better preservation of
      somatosensory evoked potentials (SSEPs) in the complement depleted animals. These
      differences were not associated with changes in leukocyte infiltration as
      evidenced by myeloperoxidase and Leukotriene B4 activity. These data demonstrate
      that depleting the complement system can improve flow and outcome following
      cerebral ischemia with reperfusion.

PMID- 9527017
TI  - The GABA(A) receptor gamma1-subunit in seizure prone (DBA/2) and resistant
      (C57BL/6) mice.
AB  - Gamma-aminobutyric acid (GABA)A receptors are the sites of action for many
      antiepileptic drugs such as benzodiazepines and barbiturates. We report the
      results of molecular cloning of the gamma1-subunit from seizure prone DBA/2J and
      resistant C57BL/6J inbred mice, and analyses of nucleotide sequences and
      expression of the gamma1-subunit messenger RNA (mRNA) in DBA/2 and C57BL/6 inbred
      mice. The mouse gamma1-subunit complementary DNA (cDNA) shares 98% similarity
      with that of the rat at the level of amino acid sequence. Northern blot
      hybridization indicates that the gamma1-subunit mRNA is expressed predominantly
      in areas other than the cerebral cortex and cerebellum and shows little change
      with postnatal development. No differences have been found for the subunit
      between DBA/2 and C57BL/6 mice either for nucleotide sequence or for level of
      expression of the subunit's mRNA in whole brain by Northern blots at 3 weeks of
      age.

PMID- 9527018
TI  - The effects of electroconvulsive shock on the short-latency somatosensory evoked
      potential in the rat.
AB  - The effects of electroconvulsive shock (ECS) were examined on the short-latency
      somatosensory evoked potential (SEP) in the awake rat. Immediately after the
      induction of generalized seizure activity (GSA), the primary cortical response
      was lost although the preceding far field thalamic component appeared to be
      preserved basically intact. Within 1 minute the cortical potential had begun to
      reemerge, albeit with an attenuated amplitude and a prolonged latency. Recordings
      made at 2 and 3 minutes revealed evidence of a slight postictal enhancement of
      the cortical potential. Within 6 minutes, a near normal waveform had been
      restored. It is concluded that the principal site of impact of ECS resides at the
      cortical level and that the somatosensory impulse is, therefore, able to traverse
      the central pathways unimpeded by GSA until it is finally blocked at the primary
      sensory cortex. The present findings are compared to previous attempts to record
      cortical SEPs from patients undergoing electroconvulsive therapy (ECT). It is
      presumed that the failure of ECT to abolish the SEP in these circumstances was
      due either to the protective role played by concurrent medication or because of a
      post-ECS delay in restarting the recordings. The relevance of the findings to an
      understanding of the physiology of electrical stunning is discussed.

PMID- 9527019
TI  - Ultrastructural studies on selected elements of the extracellular matrix in the
      developing rat lung alveolus.
AB  - As the respiratory system adapts to the extrauterine life, the extracellular
      matrix (ECM) plays an important structural and regulatory role during its
      development. Therefore the purpose of this investigation was to analyze
      ultrastructurally several elements of extracellular connective tissue during the
      process of rat lung development. Morphological observations were mainly focused
      on the terminal part of respiratory system. To outline different components of
      connective tissue network, several ultrastructural techniques were used (both
      histochemical and immunohistochemical). The distribution and amount of the
      following proteins were studied: laminin, collagen type IV, collagen fibrils
      (CFs), elastic fibers (EFs) and fibronectin (FN). Additionally localization of
      glycosaminoglycans (GAGs) was examined. The present study deals with four periods
      of lung development: pseudoglandular, canalicular, saccular and alveolar. In all
      these stages localization and amount of ECM components change rapidly. In early
      periods of lung development, the amount of connective tissue fibers was low,
      basement membranes (BMs) were incomplete, and FN was distributed nearly
      uniformly. Later when the process of lung alveoli formation begins, the number
      and thickness of both CFs and EFs rapidly increased, BMs became complete, the
      content and distribution of FN were irregular. In all stages of lung development
      GAGs were distributed in BMs and among connective tissue fibers. The results
      described in the present study summarize morphologically ECM changes occurring
      during formation of lung alveolus.

PMID- 9527020
TI  - Immunohistochemical demonstration of beta-endorphin in guinea pig sebaceous
      glands of normal skin and during immune inflammation.
AB  - Very suggestive evidence for possible role of beta-endorphin (BE) in immune
      activity has been continuously accumulated in the literature in spite of
      contradictory results about the involvement of the opiate system in immunological
      response. The reversed passive Arthus reaction (RPAR) was performed in the dorsal
      area of the guinea pig skin and immunohistochemical PAP method was applied for
      visualisation of BE. The positive BE immunoreactivity was observed in sebaceous
      gland cells (SGC) , mainly localized in the middle layer of the glands, both in
      the normal and experimental skin. The maximal intensity of immunoreactivity to BE
      in SGC during RPAR was stronger than normal. In control skin, 50% of SGC revealed
      positive immunoreactivity comparing to 60-66% in the late phase of RPAR.
      Sebaceous glands (SGs) probably take part in local homeostasis in the skin, also
      during immune inflammation.

PMID- 9527021
TI  - Distribution of mast cells along and across successive segments of the rat
      digestive tract: a quantitative study.
AB  - Density of mast cells stained by Alcian Blue at pH 0.3 was measured in the
      successive segments and the successive layers of rat digestive tract using a
      semiautomatic computerized image analysis system. The results were calculated in
      a dual way: per area of the entire layer and per area of its connective tissue
      compartment, in which the mast cells were located (extremely small number of
      intraepithelial and intramuscular mast cells was not included in the analysis).
      The distribution of mast cells in the particular layers was rather uniform with
      exception of the fundus of glandular stomach, where they were located at two
      distinct levels: in the upper quarter of the mucosa and in its lowermost zone,
      with the layer inbetween being practically free of mast cells. The quantitative
      estimation of mast cell density in the successive segments of the digestive tract
      yielded a generally similar profile irrespectively of the way of calculating the
      results, with the highest overall densities being observed in the middle segments
      (stomach, jejunum). Especially high densities of mast cells per area unit of the
      connective tissue were found in the muscularis of glandular stomach and in the
      lamina propria of small intestine and cecum. The analysis of mast cell density in
      the successive layers of the particular digestive tract segments revealed no
      clear pattern when the results were expressed per area unit of the whole layer.
      Calculation of densities per area unit of the connective tissue showed that
      lamina propria contained the most numerous mast cells in the entire small and
      large intestine, moreover, a decreasing pattern of mast cell density across the
      wall (lamina propria>submucosa>muscularis) was observed in the jejunum,
      transverse colon and rectum, suggesting that the latter way of calculation more
      reliably reflects mast cell distribution, which may result from the joint
      influence of two factors: the distance from the lumen of the digestive tract and
      the density of nerve terminals in its wall.

PMID- 9527022
TI  - Scanning electron microscopy of the egg surface of the common toad, Bufo bufo,
      following fertilization and during first cleavage.
AB  - Scanning electron microscopy was applied for surface analysis of unfertilized and
      fertilized eggs of the common toad, Bufo bufo. In unfertilized eggs two types of
      surface protrusions were found: microvilli and microfolds. 5 min post
      fertilization (pf), at the place of sperm entrance, a fertilization body appears,
      surrounded by a group of small depressions, which gradually spread over the whole
      egg surface. This phenomenon is considered to reflect structural changes of the
      egg membrane, occurring in response to cortical granule breakdown. Another
      process which follows fertilization is the disappearance of microfolds and the
      formation of microvilli. Shortly before the first cleavage, the egg surface
      smooths out and a zone of spherical microvilli becomes visible at the presumptive
      furrow region. While the cleavage furrow penetrates into the egg, microvilli
      appear at the surface of the newly forming blastomeres.

PMID- 9527024
TI  - Effect of DNA methylation on potential transcriptional activity in different
      tissues and organs of Vicia faba ssp. minor.
AB  - Routine protocol was used to isolate DNA (average size 50000 Kbp) from old/young
      leaves, cotyledons, apical buds and different zones of roots from 4 and 7 days
      old Vicia faba seedlings as well as from mature plants. The level of m5dC, as
      determined by HPLC, varies in the tested material from 22.9% to 31% and could be
      arranged in the following order: first leaves of seedlings<root<meristematic buds
      approximately = differentiated zones of root<young leaves<old leaves =
      cotyledons. This observation suggests that there is a relation between the level
      of DNA methylation and the processes of differentiation and aging of leaves.
      DNase I digestion of chromatin of interphase nuclei from different organs of
      Vicia faba (in situ nick-translation, cytophotometry) indicates that the increase
      in DNA methylation reduces potential transcriptional activity.

PMID- 9527023
TI  - Cell cycle arrest in antheridial extract-treated root meristems of Allium cepa
      and Melandrium noctiflorum.
AB  - Previous results have demonstrated that extracts derived from maturing male sex
      organs of Chara tomentosa are capable of inducing profound structural and
      functional effects upon M-phase cells in the primary root meristems of Melandrium
      noctiflorum and Allium cepa. Evident changes produced by a putative factor
      engaged in morphogenesis of antheridial filaments are manifested by: (1)
      significant shortening of chromosomes, (2) decreased mitotic indices, and (3)
      altered proportions estimated for the prophase and telophase transit times. The
      present image analysis of late G2 phase nuclei in antheridial filaments of C.
      tomentosa supports the concepts that progressive changes of their functional
      activities correspond closely to the increasing proportion of condensed
      chromatin. Cytophotometric measurements of Feulgen-stained cell nuclei in root
      meristems after a prolonged incubation in antheridial extracts revealed that
      cells which previously divided asynchronously became preferentially arrested in
      G1 (M. noctiflorum) and G2 (A. cepa). The stages at which the cells arrest are
      supposed to counterpart restriction checkpoints that prevent the initiation of
      DNA synthesis and mitosis. This assumption has been confirmed by autoradiographic
      studies using 3H-thymidine. In terms of the "Principal Control Points" (PCP)
      hypothesis, the obtained results suggest that two PCPs regulate G1-->S and G2-->M
      transition in a nuclear structure-dependent and a species-specific manner.
      Although in antheridial extract-treated roots of both M. noctiflorum and A. cepa
      there are only slight changes in the levels of chromatin condensation, the
      relative proportions of G1- and G2-arrested cells and their nuclear density
      profiles differ, as compared with the control and carbohydrate-starved plants.

PMID- 9527025
TI  - Hydrothorax in peritoneal dialysis.

PMID- 9527026
TI  - Peritoneal catheters and exit-site practices toward optimum peritoneal access:
      1998 update. (Official report from the International Society for Peritoneal
      Dialysis)

PMID- 9527028
TI  - Risk factors for developing peritonitis caused by micro-organisms of enteral
      origin in peritoneal dialysis patients.
AB  - OBJECTIVE: To investigate the risk factors associated with the development of
      peritonitis caused by enteral bacteria in peritoneal dialysis patients, including
      the prescription of gastric acid inhibitors as a potential risk factor. DESIGN:
      Retrospective single-center study. SETTING: Tertiary university hospital.
      PATIENTS AND MAIN OUTCOME MEASURES: Fifty-five patients who entered into our
      continuous ambulatory peritoneal dialysis (CAPD) program during the last 6 years
      were included. Multiple logistic regression analysis was used to establish the
      best determinants over the development of at least one episode of enteric
      peritonitis. The predictive variables included in the model were: age, gender,
      diabetic versus nondiabetic, polycystic versus nonpolycystic kidney diseases,
      history of constipation, presence or absence of moderate/severe malnutrition,
      peritoneal transport characteristics, peritoneal protein losses, rate of exit
      site infections, rate of total peritonitis, intestinal abnormalities, and
      treatment with inhibitors of gastric acid secretion. RESULTS: The total number of
      peritonitis episodes during the studied period was 88, which clustered in 34 of
      55 patients. Fourteen (16%) were caused by enteric micro-organisms in 10
      patients: Escherichia coli (6), Klebsiella sp (2), Enterobacter sp (1), and
      Enterococcus sp (5). Nine of 10 patients who developed enteric peritonitis were
      on gastric acid inhibitors (3 patients on omeprazole and 6 patients on H2
      antagonists), while 15 of 45 patients who did not develop enteric peritonitis
      were on gastric acid inhibitors (all of them on H2-blockers). There were temporal
      relationships between the start of gastric acid inhibitors and the development of
      enteric peritonitis in 6 of 9 patients who were on this medication. Four of 10
      patients who developed enteric peritonitis had diverticulosis. Ten of 45 patients
      who did not develop enteric peritonitis had been diagnosed with diverticulosis of
      the colon or sigmoid prior to entry to CAPD. The unique patient who was not on
      gastric acid inhibitors and developed enteric peritonitis, had been diagnosed
      with chronic atrophic gastritis with achlorhydria. By multiple logistic
      regression analysis, the treatment with gastric acid inhibitors was the only
      independent variable that entered into the best predictive equation over the
      development of enteric peritonitis (log likelihood ratio = -26.077, odds ratio =
      18; 95% CI odds ratio: 2 - 155). CONCLUSION: Gastric acid inhibitors may increase
      the risk for developing enteric peritonitis in peritoneal dialysis patients.

PMID- 9527027
TI  - Hyperleptinemia in patients with end-stage renal disease undergoing continuous
      ambulatory peritoneal dialysis.
AB  - OBJECTIVE: To determine whether the increased plasma leptin levels reported in
      hemodialyzed patients is a feature of end-stage renal disease or an artifact of
      hemodialysis, we studied plasma levels in patients treated exclusively by
      continuous ambulatory peritoneal dialysis (CAPD). DESIGN: Prospective comparison
      of end points in CAPD patients and matched healthy subjects. SETTING: Tertiary
      care institutional dialysis center. PARTICIPANTS: Fifty-six healthy subjects, age
      50.8 +/- 2.3 years, body mass index (BMI) 27.7 +/- 1.3 kg/m2, recruited through
      public announcement, and 36 patients with end-stage renal disease, age 51.0 +/-
      2.4 yr, BMI 28.2 +/- 1.3 kg/m2, enrolled in a CAPD treatment program.
      INTERVENTION: Four exchanges of CAPD per day, using 2.0, 2.5, or 3.0 L of
      dialysate over a period of 1 - 96 months (median 22 mth). MAIN OUTCOME MEASURES:
      The primary outcome measure was plasma leptin concentration. Secondary measures
      included plasma glucose, insulin, C-peptide, and cortisol concentrations; and
      residual renal function and dialysis adequacy (Kt/V). RESULTS: Plasma leptin
      levels in CAPD patients were 27.1 - 490 ng/mL (women) and 1.3 - 355 ng/mL (men);
      the levels in healthy subjects were 2.0 - 84.7 ng/mL (women) and 1.8 - 55.4 ng/mL
      (men). The mean leptin levels were 5-fold higher among CAPD-treated men than
      control men (49.9 +/- 18.4 vs 9.8 +/- 2.5 ng/mL, p < 0.001) and 7.5-fold higher
      among CAPD-treated women than control women (220 +/- 28.1 vs 29.3 +/- 3.7 ng/mL,
      p < 0.0001). Female gender and BMI were the strongest predictors of
      hyperleptinemia in CAPD patients. CONCLUSION: These results indicate that
      hyperleptinemia is a feature of terminal renal failure, not an artifact of
      hemodialysis.

PMID- 9527029
TI  - Autonomic function in patients on continuous ambulatory peritoneal dialysis.
AB  - OBJECTIVE: To investigate sympathetic function in the peripheries of patients on
      chronic ambulatory peritoneal dialysis (CAPD) using noninvasive techniques.
      DESIGN: Comparison of peripheral blood flow responses in sympathetic
      vasoconstrictor reflexes in CAPD patients and matched control subjects. SETTING:
      Tertiary care hospital and research institution. PATIENTS: Twenty-three
      clinically stable CAPD patients and 23 control subjects matched for age, sex, and
      drug therapy. MAIN OUTCOME MEASURES: Sympathetic activity assessed from the
      reductions in hand and foot blood flow induced by a deep breath and by body
      surface cooling. Cardiac autonomic activity measured by the changes in heart rate
      produced by deep breathing, a Valsalva maneuver, and standing from lying.
      RESULTS: A deep breath induced mean decreases in hand blood flow of 65.1% in the
      patients and 82.8% in their matched controls. Corresponding reductions in the
      foot were 46.0% and 70.0%. Body surface cooling reduced mean hand blood flow by
      50.3% in the patients and 71.8% in the control subjects. Corresponding values in
      the foot were 26.7% and 43.6%. The differences in response between the patients
      and their matched control subjects were all significant (p < 0.01). Cardiac
      autonomic function assessed by standard tests of heart rate variability was
      significantly impaired in the patients compared with the control subjects in two
      of the three tests used (p < 0.001). CONCLUSIONS: Cardiovascular autonomic
      impairment can affect the peripheral circulation as well as the heart in patients
      on dialysis, and this may have implications for cardiovascular homeostasis.

PMID- 9527030
TI  - The effect of dialysate glucose on phagocyte superoxide generation in CAPD
      patients.
AB  - OBJECTIVE: In the present study, we investigated the influence of dialysate
      glucose on superoxide (O2-) generation by peripheral and peritoneal phagocytes in
      continuous ambulatory peritoneal dialysis (CAPD) patients. DESIGN: Peripheral
      polymorphonuclear leukocytes (PMNL) and mononuclear leukocytes (MNL), and
      peritoneal cells were isolated from peripheral blood and peritoneal effluents,
      respectively, and their oxidative metabolism was assessed by measuring O2-
      generation after stimulation with a soluble stimulant [phorbol myristate acetate
      (PMA), 1 mg/mL, Sigma Chemical, St. Louis, MO, U.S.A.] using the
      chemiluminescence method. Dialysate glucose effect on O2- generation was also
      studied in vitro by exposing peripheral PMNL and MNL from healthy controls to
      peritoneal dialysis fluid (PDF) containing glucose or amino acids at a neutral pH
      for different time periods. RESULTS: The amount of O2- generation by both
      peripheral and peritoneal phagocytes in CAPD patients was significantly higher
      than that in the control, and the response was greater in patients who were
      dialyzed with high glucose dialysate than those using low glucose dialysate. In
      an in vitro study, all incubated cells, except the control, showed suppression of
      O2- generation in the early dwell time (2 hr), and subsequently showed increased
      responses (peaking at 6 hr), although lower in degree than those observed in
      vivo. In contrast, amino acid-based PDF exhibited no such effect on O2-
      generation at identical pH with similar or lower osmolality. Furthermore, the
      respective increased or decreased oxidative responses with the increased or
      decreased PDF glucose concentrations in the same patient confirmed the positive
      effect of PDF glucose on phagocyte O2- generation. CONCLUSION: It is suggested
      that increased O2- generation by peritoneal and circulating phagocytes in CAPD
      patients is at least partly due to the enhancement of hexose monophosphate shunt
      activity by increasing glucose metabolism in phagocytes, and the increased O2-
      generation might be involved in long-term complications of CAPD. Therefore, a
      suitable alternative osmotic agent is needed to provide a more physiological
      environment to minimize the adverse effects of glucose on cell functions.

PMID- 9527031
TI  - The effect of antibiotic prophylaxis on the healing of exit sites of peritoneal
      dialysis catheters in rats.
AB  - OBJECTIVE: To evaluate the influence of intraperitoneal (i.p.) antibiotic (AB)
      prophylaxis on the quality of healing and infection rates of exit sites in
      peritoneal dialysis catheters. STUDY DESIGN: Twenty-one Sprague-Dawley rats were
      dialyzed 3 times per day for 6 weeks. Dianeal solution containing AB was used for
      all the rats during the first 5 days. The animals were randomized on the sixth
      day into three groups: group A (AB-free after randomization), group B (AB for 3
      weeks), and group C (AB during 6 weeks). Scores were given to each exit site
      according to the observation. Mean scores from each group were compared in an
      attempt to find significant differences between the groups. Dialysate and exit
      site drainage samples were taken weekly for microbiology. RESULTS: Eight episodes
      of peritonitis were diagnosed, six in group A and two in group B. The most common
      bacteria causing peritonitis were gram-negative rods. The mean scores were not
      significantly different between groups C and B throughout the study, even after
      the discontinuation of the prophylaxis. Group A, when compared to the other two
      groups, had significantly higher scores after the second week and throughout the
      rest of the study. CONCLUSION: Intraperitoneal antibiotic prophylaxis for 3 weeks
      after catheter implantation is an effective way to prevent early colonization of
      exit sites, providing a better healing quality and lower incidence of catheter
      related infection. Although the extension of the prophylaxis for 6 weeks seems to
      be beneficial, it was not statistically proven in this study.

PMID- 9527033
TI  - The Italian Registry of Pediatric Chronic Peritoneal Dialysis: a ten-year
      experience with chronic peritoneal dialysis catheters.
AB  - OBJECTIVE: To analyze the data from 347 peritoneal catheters implanted in 249
      pediatric patients aged < or = 15 years at start of chronic peritoneal dialysis
      (CPD). DESIGN: Restrospective study of the data collected between 1986 and 1995,
      in 20 dialysis centers, from the Italian Registry of Pediatric Chronic Peritoneal
      Dialysis. Data collection for each pediatric catheter included: catheter type,
      site and technique of insertion, complications, duration, and reason for removal
      or replacement. RESULTS: Fifty catheters were inserted in patients under 2 years
      of age, 50 in patients aged 2 - 5 years and 247 in patients over 5 years of age.
      Catheter types included 307 (88.5%) Tenckhoff (286 double cuff, 21 single cuff)
      and 40 (11.5%), double-cuff, Valli-type catheters. All catheters were surgically
      implanted and omentectomy was performed in 83.5% of cases; the entry-site was in
      the midline in 136 cases (39.2%) and paramedian in 211 (60.8%). During 6076 CPD
      months we observed 274 catheter-related complications: 182 catheter infections
      (exit-site and/or tunnel infection), 23 leakages, 19 obstructions, 19 cuff
      extrusions, 14 dislocations, 6 hemoperitoneum, 10 other (incidence of one
      complication every 21.8 dialysis-months). A significant reduction of catheter
      related complications occurred in the last five years, compared with the first 5
      years. One hundred and six catheters were removed due to catheter-related causes:
      infection (83 cases), obstruction (11), dislocation (4), outer-cuff extrusion
      (3), leakage (2), bowel incarceration (2), and bowel infarction (1). Catheter
      survival was 72.2% at 12 months, 52.3% at 24 months, 32.8% at 36 months, and
      25.7% at 48 months. Significantly lower catheter survival was found in younger
      children (0 - 2 years) compared with two other age groups (2 - 5 years, and > 5
      years). No significant correlation was found between catheter survival and
      catheter entry-site (midline vs paramedian). CONCLUSIONS: Catheter-related
      infections were confirmed to be the most common complication and most frequent
      cause of peritoneal catheter removal. In addition, catheter survival rate was
      worse in younger children, indicating that more effort should be made to improve
      peritoneal catheter survival particularly in this age group.

PMID- 9527032
TI  - The absence of toxicity in intraperitoneal iron dextran administration: a
      functional and histological analysis.
AB  - OBJECTIVE: To determine the influence of iron dextran intraperitoneal
      administration on the function and histology of the peritoneum in rats undergoing
      chronic peritoneal dialysis. DESIGN: Prospective, randomized experimental study.
      MATERIALS: Fifty-four Sprague-Dawley rats were divided into five groups: 3 study
      groups--high dose group (H), n = 12; intermediate dose (M), n = 12; and low dose
      group (L), n = 12--a dialysis control group (D), n = 12; and a tissue control
      (C), n = 7. INTERVENTIONS: The study groups were given Dianeal containing iron
      dextran in a concentration of 0.5, 0.25, and 0.125 mg/L (groups H, M, and L
      respectively). Group D was given standard Dianeal. Group C was never dialyzed.
      MAIN OUTCOME MEASURES: A 2-hour peritoneal equilibrium test (PET) was performed
      on the eighth day, at 3 months, and at 6 months. After the final PET, the animals
      were sacrificed and the peritoneal membrane was evaluated by gross inspection and
      light microscopy (silver, prussian blue, and trichrome staining). RESULTS:
      Peritoneal transport of small solutes followed the same pattern in all groups,
      increasing over time. The peritonitis index was similar in the groups. No iron
      deposits or morphologic differences were seen in the gross inspection of the
      peritoneal cavity. No peritoneal iron deposition was detected in the histological
      analysis with prussian blue staining. No differences were noted in the light
      microscopic analysis of the mesothelial cell layer (silver staining), nor did the
      morphometric analysis of the submesothelial space show any differences in
      thickness between the groups. CONCLUSION: These findings suggest the absence of
      toxic effects of iron dextran on the peritoneal cavity of rats in the
      concentrations studied. Further studies should be performed to evaluate the
      effectiveness of these dosages delivered intraperitoneally to maintain iron
      homeostasis.

PMID- 9527034
TI  - Is abnormal polymorphonuclear leukocyte function in end-stage renal failure
      associated with increased incidence of CAPD peritonitis?

PMID- 9527035
TI  - Hypermagnesemia in CAPD. Relationship with parathyroid hormone levels.

PMID- 9527036
TI  - Peritonitis associated with massive pneumoperitoneum from failure to flush.

PMID- 9527037
TI  - Gastrointestinal side effects of ramipril in peritoneal dialysis patients.

PMID- 9527038
TI  - Risks of gastrostomy tubes in children on peritoneal dialysis.

PMID- 9527039
TI  - Cytokines (Cys) and C-reactive protein (CRP) in CAPD patients.

PMID- 9527040
TI  - VRE and empirical vancomycin for CAPD peritonitis: use at your own/patient's
      risk.

PMID- 9527041
TI  - Recurrent hemoperitoneum in a middle-aged woman on CAPD.

PMID- 9527042
TI  - Literature. January-February 1998.

PMID- 9527044
TI  - Introduction to histology of the cell cycle.

PMID- 9527043
TI  - Nursing application: Establish protocols of patient care based on published
      research.

PMID- 9527045
TI  - Cell cycle dependent aneuploidy induction by X-rays in vitro in human
      lymphocytes.
AB  - Although ionising radiation mainly induces DNA strand breaks leading to
      chromosomal aberrations, there are indications that it also might induce
      numerical chromosome aberrations (aneuploidy). The existing data, however, do not
      provide evidence for a mechanism. To assess the relative sensitivity of the G1
      vs. G2 cellular targets, whole blood cultures of lymphocytes were irradiated in
      vitro with different doses of X-rays (0.5, 1 and 2 Gy). The lymphocytes were
      harvested after cytochalasin-B blockade to allow the selective study of
      binucleated cells, having undergone only one division in culture. Harvesting was
      performed at different sampling times (70, 74, and 78 hours). To evaluate the
      micronuclei, regarding whole chromosomes or acentric fragments, an
      oligonucleotide probe that recognises the centromeric region of all human
      chromosomes was used. The relative percentage of centromere-positive micronuclei
      ranged from 5 up to 18% depending on the cell cycle stage and on the received
      dose. Cells exposed during the G1 phase exhibited a slightly higher frequency of
      centromere-positive micronuclei than cells that were in G2 at the time of
      exposure. G1 exposure induced a centromere-positive micronuclei dose-effect
      relationship that was not observed after G2 exposure. The observed difference in
      response of both phases on the centromere-positive micronuclei yields may be due
      to the involvement of different targets.

PMID- 9527046
TI  - Partitioning of cytoplasmic organelles during mitosis with special reference to
      the Golgi complex.
AB  - During mitosis, not only the genetic material stored in the nucleus but also the
      constituents of the cytoplasm should be equally partitioned between the daughter
      cells. For this sake, the dividing cell goes through an extensive structural
      reorganization and transport along the endocytic and exocytic pathways is
      temporarily arrested. Early in prophase, the radiating array of cytoplasmic
      microtubules disassembles and the membrane systems of the secretory apparatus
      start to split up. In metaphase, the nuclear envelope fragments and the
      condensing chromosomes associate with the forming mitotic spindle. The cisternal
      and tubular elements of the endoplasmic reticulum and the Golgi complex break
      down into small vesicles, presumably as the result of an imbalance between
      vesicle budding and fusion. In anaphase, the two sets of chromosomes are pulled
      apart and a cleavage furrow forms halfway between the spindle poles. Since most
      organelles occur in multiple and widely dispersed copies at this stage, they will
      be evenly distributed between the daughter cells. During telophase and
      cytokinesis, the preceding fragmentation process is reversed. A nuclear envelope
      reappears around the chromosomes and cytoplasmic microtubules reassemble. The
      endoplasmic reticulum is rebuilt as a continuous system of flattened cisternae
      and tubules. Stacks of Golgi cisternae arise from small vesicles and are
      rearranged in an interconnected network. In parallel, the biosynthetic functions
      of the cell are normalized and intracellular membrane traffic is resumed.

PMID- 9527047
TI  - Fluorescence microscopy of etched methacrylate sections improves the study of
      mitosis in plant cells.
AB  - Etched sections of methacrylate infiltrated plant tissue [Gubler (1989) Cell
      Biol. Int; Rep., 13:137-145; Baskin et al. (1992) Planta, 187:405-413] offer many
      advantages over the more traditional squash technique of Wick et al. [(1981) J.
      Cell Biol. 89:685-690] for immunofluorescence microscopic investigation of the
      plant cytoskeleton, especially during mitosis. These advantages include: (1)
      unimpeded access of antibody probes, (2) confocal-like imaging without the
      expense of confocal equipment, (3) maintenance of organ architecture as well as
      intracellular structure, (4) the ability to independently examine separate focal
      planes with the same or multiple antibody(s) or other labelling compounds, and
      (5) the ability to archive unetched sections, polymerized or non-polymerized
      infiltrated tissue. In this paper examples of staining of various microtubule
      cytoskeletal and mitotic proteins are shown in a variety of methacrylate embedded
      plant tissues.

PMID- 9527048
TI  - Germ cell kinetics during early ovarian differentiation: an analysis of the
      oogonial cell cycle and the subsequent changes in oocyte development during the
      onset of meiosis in the rat.
AB  - The aim of this study was the comparison between the mitoses of oogonia and the
      initial stages of oocyte meiosis. The structural alterations that the germ cell
      chromatin undergoes during the oogonial mitosis have been compared with those
      occurring during the G1- and S-phase just before meiosis. Using plastic embedded
      1-microm sections of fetal rat ovaries (embryonic days = ED 14-20) labeled with
      3H-thymidine and re-embedded for electron microscopy, a study of the structural
      conditions of the nuclear chromatin has been combined with a kinetic analysis of
      the oogonial cell cycle and the transitional period into the meiotic prophase.
      After ovarian differentiation (ED 14) the oogonia show a non-clonal, but strong
      proliferation. On ED 16, proliferation changes to a clonal pattern and decreases
      during ED 17. A final increase in 3H-thymidine incorporation on ED 18
      characterizes the meiotic S-phase. On ED 19 the nuclear labeling drops to zero.
      The mitotic cycle of the oogonia lasts 16.5 hr and can be divided into 11 stages
      according to the concept of El-Alfy and Leblond [(1988) Am. J. Anat., 183:45-56]
      on the basis of the chromatin pattern. The S-phase (10.0 hours) extends from the
      telophase-interphase transition through the interphase to early prophase. The
      postmitotic G1- and S-phases show a more extensive duration, respectively 10 and
      11.5 hours, and differ from their oogonial counterparts by the spherical shape of
      the nuclei from the very beginning. The chromatin pattern is similar until the
      end of the S-phase and lacks any prophase-like, preleptotenal chromatin
      condensation before the oocytes exhibit (pre-) leptotenal structures. Once the
      germ cell has completed a sequence of clonal mitotic divisions, it irrevocably
      progresses into meiosis. During an extended postmitotic period, the structural
      characteristics of meiosis emerge stepwise.

PMID- 9527050
TI  - Correlations between mitotic and apoptotic indices, number of interphase NORs,
      and histological grading in squamous cell lung cancer.
AB  - Proliferative activity of tumors is strongly associated with prognosis and
      response to therapy. The reason for faster and uncontrolled growth rate of tumors
      compared with normal tissue may be caused by the greater proliferation of cells,
      the smaller rate of cell death, or both. Cell production vs. cell loss rates, and
      their correlation with a grade of tumor cell differentiation (G) was estimated in
      45 cases of squamous cell lung cancers (SCLC) by the use of mitotic indices (MI),
      number of interphase NORs, and apoptotic indices (AI) as parameters. The mitotic
      figures as well as apoptotic cells were observed on paraffin sections (4-microm
      thick) stained with haematoxylin and eosin, and with Feulgen reaction with Schiff
      type reagent containing 0.5% Toluidine Blue. According to our results, all three
      parameters distinguish significantly (P < 0.05) between well and moderately or
      poorly differentiated groups, but not between the first two groups, and clearly
      discriminate between low- and high-grade malignancy. These results suggest
      classification of squamous cell lung cancers into two groups, a group of low and
      a group of high proliferative activity, despite their morphological appearance.
      Regression analysis revealed a significant (P < 0.0005) correlation between MI
      and AgNOR counts per cell nucleus as proliferative markers and AI as a marker of
      cell loss. The number of mitoses and apoptoses, especially when they are
      expressed as a percentage of the total number of tumor cells, are markers of
      tumor proliferation rate. They both can be used in biofunctional staging, based
      on cell kinetics, to provide more prognostic information about lung cancers than
      clinicopathological staging.

PMID- 9527049
TI  - GABA, GAD, and GABA(A) receptor alpha4, beta1, and gamma1 subunits are expressed
      in the late embryonic and early postnatal neocortical germinal matrix and
      coincide with gliogenesis.
AB  - Increasing evidence indicates that the classical, fast-acting neurotransmitter
      gamma-amino butyric acid (GABA) may initially act as morphogen in cell
      proliferation and differentiation via specific receptors. In view of the
      potential roles for GABA in central nervous system development, we examined the
      expression of GABA, GABA(A) receptor beta1 and gamma1 subunits by
      immunocytochemistry and the expression of transcripts for two GABA-synthesizing
      enzymes, glutamate decarboxylase (GAD65, GAD67 mRNAs), and for alpha4, beta1, and
      gamma1 subunits of GABA(A) receptor by in situ hybridization in the developing
      neocortex. Tissue sections were taken from embryonic days (E) 17 and E20 embryos
      and newborn rats (P0). The embryos' mothers and newborn rats had been injected
      with 5-bromo-2'-deoxyuridine (BrdU) and had survived for 2 hours. At E17, BrdU
      positive cells were largely restricted in the synthetic zone at the ventricular
      margin when cortical neurogenesis was still active. GAD mRNAs and GABA
      immunoreactivity were detected in the subventricular zone, while alpha4, beta1,
      and gamma1 subunits were abundant in the ventricular zone. At E20 and P0, when
      neurogenesis had largely ceased and gliogenesis had commenced, BrdU-positive
      cells were found throughout the ventricular zone with GABA, GAD mRNAs, and
      alpha4, beta1, and gamma1 subunits. GABA, GAD mRNAs and alpha4, beta1, and gamma1
      subunit signals intensified in the ventricular zone from E17 to P0 as gliogenesis
      proceeded. Thus, specific components of a putative GABAergic circuit are
      expressed in cells of the ventricular zone during the late embryonic/early
      postnatal period coincident with gliogenesis, suggesting a role for GABA in glial
      cell proliferation.

PMID- 9527051
TI  - Nuclear morphology during the S phase.
AB  - In order to evaluate at the ultrastructural level the chromatin arrangement
      during the S phase of the cell cycle, the detection of Bromodeoxyuridine (BrdU)
      by immunogold has been performed in synchronized 3T3 fibroblasts, regenerating
      liver, and Friend Leukemia Cells (FLC). After a 5-minute BrdU pulse, this label
      is detected in 10-nm-wide fibers, organized as lacework and assumed to be
      replication units. In the early part of the S phase, DNA replication units are
      localized exclusively in the dispersed chromatin domains far from the nuclear
      envelope. In the middle S, replication occurs at the border between condensed and
      dispersed chromatin and, finally, in late S, it mainly occurs in perinuclear
      heterochromatin regions. After replication, the 10-nm fibers can condense in
      heterochromatin without translocation. Chromatin is highly dispersed in early S
      and computer image analysis shows an increase in condensed chromatin areas
      ranging from 13 to 18% at the end of the S phase with a temporal and
      morphological pattern of distribution characteristic for each cell type. Scanning
      transmission electron microscopy demonstrates a regular and repetitive structure
      of dispersed chromatin, represented by a ring-like arrangement of the 10-nm
      fibers; assuming the same spatial distribution, gold particles that identify
      incorporated BrdU confirm this organization. By evaluating the organization and
      the distribution of DNA replication units during S phase, the results suggest
      that DNA replication occurs at a nucleosomal-like fiber level and that
      replicating enzymes machinery moves over a fixed template.

PMID- 9527052
TI  - Utility of FDG-PET for investigating unexplained plasma CEA elevation in patients
      with colorectal cancer.
AB  - OBJECTIVE: To assess the potential role of positron emission tomography (PET)
      with 2-[18F]fluoro-2-deoxy-D-glucose (FDG) in patients with unexplained rising
      carcinoembryonic antigen (CEA) levels after the treatment of colorectal cancer.
      BACKGROUND: A rising CEA level after the resection of colorectal cancer is an
      early indicator of tumor recurrence. However, conventional imaging techniques
      have limited sensitivity for detecting recurrent disease in such patients.
      Especially after surgical intervention, FDG-PET is rapidly gaining an important
      role in establishing the extent of disease in the oncology patient. METHODS:
      Twenty-two patients with abnormal CEA levels and normal results of conventional
      methods of tumor detection were studied with FDG-PET. The PET results were
      compared with pathologic findings (n = 9) and long-term radiologic and clinical
      follow-up (n = 13). RESULTS: FDG-PET was abnormal in 17 of 22 patients. Tissue
      sampling was available in 7 of these 17 patients; all of these had recurrent
      disease. Definitive curative surgical intervention was performed in four
      patients. Subsequent dedicated imaging findings and clinical course confirmed the
      presence of extensive disease in 8 of the remaining 10 patients; the PET results
      in the other 2 patients were considered falsely positive. FDG-PET was negative in
      5 of 22 patients. No disease was found by tissue sampling (n = 2) and clinical
      follow-up (n = 3). Overall, the positive-predictive value for PET was 89%, (15 of
      17) and the negative-predictive value was 100% (5 of 5). CONCLUSIONS: When
      conventional examinations are normal, FDG-PET is a valuable imaging tool in
      patients who have a rising CEA level after colorectal surgery.

PMID- 9527053
TI  - Future of positron-emission tomography in oncology.

PMID- 9527054
TI  - Laparoscopic surgery and the systemic immune response.
AB  - OBJECTIVE: The authors review studies relating to the immune responses evoked by
      laparoscopic surgery. SUMMARY BACKGROUND DATA: Laparoscopic surgery has gained
      rapid acceptance based on clinical grounds. Patients benefit from faster
      recovery, decreased pain, and quicker return to normal activities. Only more
      recently have attempts been made to identify the metabolic and immune responses
      that may underlie this clinical success. The immune responses to laparoscopy are
      now being evaluated in relation to the present knowledge of immune responses to
      traditional laparotomy and surgery in general. METHODS: A review of the published
      literature of the immune and metabolic responses to laparoscopy was performed.
      Laparoscopic surgery is compared with the traditional laparotomy on the basis of
      local and systemic immune responses and patterns of tumor growth. The impact of
      pneumoperitoneum and insufflation gases on the immune response is also reviewed.
      CONCLUSIONS: The systemic immune responses for surgery in general may not apply
      to laparoscopic surgery. The body's response to laparoscopy is one of lesser
      immune activation as opposed to immunosuppression.

PMID- 9527055
TI  - Laparoscopically assisted anterior resection for diverticular disease: follow-up
      of 100 consecutive patients.
AB  - PURPOSE: The objectives of this study were to refine the technique of
      laparoscopically assisted anterior resection (LAR) for diverticular disease and
      to analyze the morbidity and mortality rates, and longer term follow-up of the
      first 100 consecutive patients. METHODS: Data were collected prospectively, and
      follow-up was performed by an independent assessor using a standardized
      questionnaire. RESULTS: The median duration of surgery was 180 minutes, the
      median time for passage of flatus was 2 days after surgery, and the median length
      of hospital stay was 4 days. Overall, the morbidity rate was 21%, and the wound
      infection rate was 5%. There were no deaths. Eight patients underwent open
      laparotomy. The rate of complications was significantly greater in the latter
      group of patients (75%) than in those who underwent laparoscopy (16%, p = 0.002).
      The comparison between the first 20 cases and the last 20 patients revealed a
      significantly shorter duration of surgery (median 225 min. vs. 150 min.; p <
      0.0001) and decreased length of stay (6 days vs. 4 days, p < 0.0001). Apart from
      a nonsignificant increase in the length of surgery, there were no differences in
      other study parameters when comparisons were made between those patients who
      underwent LAR for complicated diverticular disease and those patients who
      underwent uncomplicated diverticular disease. FOLLOW-UP: Ninety patients were
      available for follow-up at a median time of 37 months. Ninety-three percent of
      the patients reported that the surgery had improved their symptoms. No patient
      required hospitalization, and no one was treated with antibiotics for recurrent
      symptoms. CONCLUSION: Laparoscopically assisted anterior resection for
      diverticular disease has acceptable morbidity and mortality rates and a median
      postoperative hospital stay of only 4 days. Follow-up investigations revealed no
      recurrence of diverticulitis, and patients reported satisfaction regarding
      cosmetic and functional results.

PMID- 9527056
TI  - Indications for and outcomes of cholecystectomy: a comparison of the pre and
      postlaparoscopic eras.
AB  - PURPOSE: Examine changing patient characteristics and surgical outcomes for
      patients undergoing cholecystectomy at five community hospitals in 1989 and 1993.
      PROCEDURES: In a retrospective chart review, data were gathered regarding
      gallstone disease severity, type of admission, patient age, number of
      comorbidities, American Society of Anesthesiologists (ASA) Physical Status
      Classification, length of stay, and multiple outcomes of surgery. MAIN FINDINGS:
      The volume of nonincidental cholecystectomies increased 26%, from 1611 in 1989 to
      2031 in 1993. Nearly all of the increase occurred among patients with
      uncomplicated cholelithiasis and with elective admissions. In 1993, lengths of
      stay were significantly shorter and percentages of complications were
      significantly lower for infectious, cardiac, pulmonary, and gastrointestinal
      complications when controlling for patient case-mix characteristics. There were
      more major intraoperative complications (unintended wounds or injuries to the
      common bile duct, bowel, blood vessel(s), or other organs) in 1993. CONCLUSIONS:
      Different types of patients underwent cholecystectomy in 1993 compared with
      patients in 1989, which supports the hypothesis of changing thresholds.
      Statements supporting the safety of cholecystectomy in the laparoscopic era were
      borne out when controlling for differences in patient characteristics.

PMID- 9527057
TI  - Preoperative assessment for laparoscopic cholecystectomy: feasibility of using
      spiral computed tomography.
AB  - OBJECTIVE: The authors investigated the preoperative feasibility of using spiral
      computed tomography (SCT) after intravenous infusion cholangiography (IVC-SCT)
      for laparoscopic cholecystectomy. SUMMARY BACKGROUND DATA: In laparoscopic
      cholecystectomy, the aberrant or unusual anatomy of the bile duct and severe
      inflammation or adhesions around the gallbladder sometimes require a conversion
      to open surgery. METHODS: Laparoscopic cholecystectomies (LC's) were attempted on
      440 patients, and preoperative IVC-SCT also was attempted in all of these
      patients. Using this spiral scanning technique, the bile ducts, cystic duct, and
      gallbladder were assessed for contour abnormalities, relative position, and
      filling defects. Forty-seven patients were diagnosed with having stones in their
      common bile duct or common hepatic duct. RESULTS: Three-hundred eighty-seven
      patients out of the 440 patients (88.0%) who were subjected to IVC-SCT had the
      length and course of their cystic duct successfully determined. Anomalous unions
      of the cystic duct were seen in 59 (15.2%) of 387 patients with respect to the
      operative findings, and 48 of 440 patients (10.9%) had severe adhesions to
      Calot's triangle and the surrounding tissues. In these 48 patients, 45 patients
      (94%) had a nonvisualized cystic duct on IVC-SCT. The preoperative assessment of
      the feasibility (dense adhesions obscuring Calot's triangle) of using IVC-SCT
      demonstrated that the sensitivity, specificity, and accuracy were 93%, 98%, and
      94%, respectively. Five patients had to be converted to open surgery, and the
      overall morbidity rates for patients undergoing laparoscopic cholecystectomy was
      0.9% (4 of 440). CONCLUSIONS: The most important factor in assessing the
      feasibility of using laparoscopic cholecystectomy is not the nonvisualized
      gallbladder, but the nonvisualized cystic duct on IVC-SCT. IVC-SCT may be of
      benefit to those patients scheduled to undergo laparoscopic cholecystectomy.

PMID- 9527058
TI  - Esophagectomy for carcinoma of the esophagus in the elderly: results of current
      surgical management.
AB  - OBJECTIVE: This study aims to evaluate the risk of esophagectomy in the elderly
      compared with younger patients and to determine whether results of esophagectomy
      in the elderly have improved in recent years. SUMMARY BACKGROUND DATA: An
      increased life expectancy has led to more elderly patients presenting with
      carcinoma of the esophagus in recent years. Esophagectomy for carcinoma of the
      esophagus is associated with significant morbidity and mortality, and advanced
      age is often considered a relative contraindication to esophagectomy despite
      advances in modern surgical practice. METHODS: The perioperative outcome and long
      term survival of 167 elderly patients (70 years or more) with esophagectomy for
      carcinoma of the esophagus were compared with findings in 570 younger patients
      with esophagectomy in the period 1982 to 1996. Changes in perioperative outcome
      and survival between 1982 to 1989 and 1990 to 1996 were separately analyzed.
      RESULTS: The resection rate in the elderly was 48% (167/345), lower than the 65%
      (570/874) resection rate in younger patients (p < 0.001). There were
      significantly more preoperative risk factors and postoperative medical
      complications in the elderly, but no significant differences were observed in
      surgical complications. The 30-day mortality rate was higher in the elderly
      (7.2%) than in younger patients (3.0%) (p = 0.02), but the hospital mortality
      rate was not significantly different in the elderly (18.0%) and younger age
      groups (14.4%) (p = 0.27). The long-term survival after curative resection in
      elderly patients was worse than younger patients (p = 0.01). However, when deaths
      from unrelated medical conditions were excluded from analysis, survival was
      similar between the two age groups (p = 0.23). A comparison of data for the
      periods 1982 to 1989 and 1990 to 1996 revealed that the resection rate had
      increased from 44% to 54% in the elderly, with significantly fewer postoperative
      complications and lower 30-day and hospital mortality rates. Long-term survival
      has also improved, although this has not reached a statistically significant
      level. CONCLUSIONS: With current surgical management, esophagectomy for carcinoma
      of the esophagus can be carried out with acceptable risk in the elderly, but
      intensive perioperative support is required. The improved results of
      esophagectomy in the elderly in recent years are attributed to increased
      experience and better perioperative management. Long-term survival was similar to
      that of younger patients, excluding deaths caused by unrelated medical
      conditions.

PMID- 9527059
TI  - Prognostic value of platelet-derived growth factor-A (PDGF-A) in gastric
      carcinoma.
AB  - OBJECTIVE: Because our previous study indicated that PDGF-A mRNA expression in
      biopsy specimens might identify a subgroup of high-risk patients with gastric
      carcinoma, in this study we analyzed the prognostic value of platelet-derived
      growth factor-A (PDGF-A) gene expression in gastric carcinoma biopsy specimens.
      METHODS: Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to
      analyze the PDGF-A gene expression in 65 gastric carcinoma endoscopic biopsy
      specimens. The 65 patients were divided into a PDGF-A-positive group (29
      patients) and a PDGF-A-negative group (36 patients). RESULTS: On the basis of 2
      year follow-up data, the PDGF-A-positive group demonstrated a shorter overall
      survival rate compared with the PDGF-A-negative group (p < 0.0001). A similar
      correlation was found in 34 advanced-stage patients (p = 0.003) and in 24
      advanced-stage patients who underwent a curative resection (p = 0.003).
      Multivariance analysis indicated that the transcription of PDGF-A gene is a
      potent prognostic factor that is independent of the traditional pathologic
      parameters. CONCLUSIONS: Expression of PDGF-A mRNA in gastric biopsy specimens
      may be a new preoperative prognostic parameter in gastric carcinoma.

PMID- 9527060
TI  - Isolated tumor cells are frequently detectable in the peritoneal cavity of
      gastric and colorectal cancer patients and serve as a new prognostic marker.
AB  - OBJECTIVE: To evaluate the prognostic significance of isolated tumor cells
      detected by a panel of various monoclonal antibodies. SUMMARY BACKGROUND DATA:
      Previously, we showed by using immunocytology that cancer cells are frequently
      found in bone marrow and peritoneal cavity samples of gastrointestinal cancer
      patients. METHODS: Findings in bone marrow and peritoneal cavity samples were
      compared and correlated with the 4-year survival rate of 84 gastric and 109
      colorectal patients with cancer. RESULTS: Although positive results in the bone
      marrow showed little prognostic significance, the peritoneal cavity results
      correlated with the 4-year survival rate (gastric cancer: p = 0.0038; colorectal
      cancer: p = 0.0079). Additionally, in subgroups of patients with early (gastric
      cancer: p = 0.02, colorectal cancer: p = 0.48) and advanced (gastric cancer: p =
      0.02, colorectal cancer: p < 0.0001) tumor stages, a correlation of
      immunocytologic findings and the survival rate was seen. CONCLUSIONS: The
      detection of minimal residual disease in the peritoneal cavity serves as a new
      prognostic marker.

PMID- 9527061
TI  - Preoperative hyperthermia combined with radiochemotherapy in locally advanced
      rectal cancer: a phase II clinical trial.
AB  - OBJECTIVE: A prospective phase II study was performed to determine the
      feasibility and efficacy in terms of response rate, resectability, and morbidity
      in patients with locally advanced rectal cancer who received preoperative
      regional hyperthermia combined with radiochemotherapy (HRCT). SUMMARY BACKGROUND
      DATA: Recent studies suggest that preoperative radiochemotherapy in locally
      advanced rectal cancer can induce downstaging, but after resection the incidence
      of local recurrences remains high. Hyperthermia (HT) may add tumoricidal effects
      and improve the efficacy of radiochemotherapy in a trimodal approach. PATIENTS
      AND METHODS: Thirty-seven patients with histologically proven rectal cancer and
      T3 or T4 lesions, as determined by endorectal ultrasound and computed tomography,
      entered the trial. 5-Fluorouracil (300-350 mg/m2) and leucovorin (50 mg) were
      administered on days 1 to 5 and 22 to 26. Regional HT using the SIGMA 60
      applicator (BSD-2000) was given once a week before radiotherapy (45 Gy with 1.8
      Gy fractions for 5 weeks). Surgery followed 4 to 6 weeks after completion of
      HRCT. RESULTS: Preoperative treatment was generally well tolerated, with 16% of
      patients developing grade III toxicity. No grade IV complications were observed.
      The overall resectability rate was 32 of 36 patients (89%), and 31 resection
      specimens had negative margins (R0). One patient refused surgery. In 5 patients
      (14%), the histopathologic report confirmed no evidence of residual tumor (pCR).
      A partial remission (PR) was observed in 17 patients (46%). The survival rate
      after 38 months was 86%. In none of the patients was local recurrence detected
      after R0(L), but five patients developed distant metastases. CONCLUSION:
      Preoperative HRCT is feasible and effective and may contribute to locoregional
      tumor control of advanced rectal cancer, which is to be proven in an ongoing
      phase III trial.

PMID- 9527062
TI  - Effect of glucagon on protein synthesis in human rectal cancer in situ.
AB  - OBJECTIVE: The purpose of this study was to determine the effect of glucagon or
      placebo on the rate of tumor fractional protein synthesis in situ in patients
      with localized rectal cancer who were not malnourished, demonstrated normal
      glucagon concentrations, and could therefore be used as a model to study the
      glucagon effect. SUMMARY BACKGROUND DATA: Cancer cachexia is associated with an
      increased concentration of counterregulatory hormones, including glucagon. This
      altered hormonal milieu may not only contribute to malnutrition, but also promote
      tumor growth, because previous experimental work suggests that glucagon can cause
      human colorectal tumor cells to proliferate. Corresponding mechanisms in vivo
      have, thus far, not been investigated. METHODS: Advanced mass spectrometry
      techniques (capillary gas chromatography [GC]/combustion isotope ratio mass
      spectrometry [IRMS]) were used to determine directly the incorporation rate of 1
      [13C]-leucine into tissue protein. Because GC/IRMS requires only a small sample
      volume, three consecutive endoscopic biopsies could be obtained from the same
      tumor to determine isotopic enrichments at baseline, after a 4-hour glucagon
      infusion (3 ng/kg/min), or after placebo. RESULTS: In patients with localized
      rectal cancer, glucagon caused the tumor fractional protein synthetic rate to
      double (2.25+/-0.49 %/hr, p < 0.05 vs. 1.16+/-0.30 basal). In contrast, tumor
      protein synthesis declined over time in controls (placebo) (0.67+/-0.09 %/hr, p <
      0.05 vs. 1.11+/-0.16 basal). CONCLUSIONS: Tumor protein synthesis and growth can
      be stimulated by glucagon in situ. Therefore, elevated glucagon concentrations in
      cachectic cancer patients should be considered detrimental and attempts made to
      prevent this specific response of the body to the malignant disease.

PMID- 9527063
TI  - Marked elevation of serum interleukin-6 in patients with cholangiocarcinoma:
      validation of utility as a clinical marker.
AB  - OBJECTIVE: To determine if the serum level of interleukin-6 (IL-6) was elevated
      in patients with hepatic malignancies or correlated with radiologic tumor burden.
      SUMMARY BACKGROUND DATA: High serum levels of IL-6 signify an adverse prognosis
      in many patients with cancer. IL-6 is a growth factor for bile duct epithelium.
      METHODS: Using bioactive and enzyme-linked immunosorbent assays, serum level of
      IL-6 was measured in 35 healthy adults and in 60 patients presenting for
      definitive management of cholangiocarcinoma (CC) (15 patients), hepatocellular
      carcinoma (HCC) (14), metastatic colorectal cancer (MCRC) (26), and benign
      biliary disease (BBD) (5). Patients with clinical conditions known to raise the
      serum level of IL-6 were excluded. Tumor burden was calculated from concurrent
      computed tomography scans. IL-6 levels were measured 2 weeks after resection in 3
      CC patients. Secretion of IL-6 was examined in 3 human CC cell lines. RESULTS: An
      elevated level of bioactive IL-6 was detected in every patient with CC and in 13
      of 14 patients with HCC, 14 of 26 patients with MCRC, 2 of 5 patients with BBD,
      and 3 of 35 healthy adults. Median and mean levels of bioactive IL-6 were higher
      in CC than in other neoplasms (p < 0.026) and for all tumor groups differed from
      healthy adults (p < or = 0.026). IL-6 level was elevated more often in primary
      than in secondary liver neoplasms (p = 0.02), distinguished patients with CC or
      MCRC from BBD (p = 0.014 and 0.031, respectively), correlated with tumor burden
      in CC (p < 0.001), and dropped sharply after CC resection. CC line SG231 secreted
      bioactive IL-6. CONCLUSIONS: In selected patients, a high serum level of IL-6
      marks patients with CC and correlates with tumor burden both before and after
      resection. IL-6 levels are elevated in patients with other liver neoplasms and
      may distinguish patients with hepatic malignancies from those with benign
      disease.

PMID- 9527064
TI  - The pattern of infiltration at the proximal border of hilar bile duct carcinoma:
      a histologic analysis of 62 resected cases.
AB  - OBJECTIVE: To clarify the importance of different patterns of infiltration at the
      proximal border of hilar bile duct carcinomas. SUMMARY BACKGROUND DATA: There are
      few detailed pathologic studies on the proximal resection margins in patients
      with hilar bile duct carcinoma. METHODS: Serial sections of 62 specimens of
      resected hilar bile duct carcinoma were examined histologically to determine the
      involved layers and routes of invasion at the proximal border. The degree of
      cancer extension was determined, and the relation between the length of the tumor
      free resection margin and postoperative anastomotic recurrences was analyzed.
      RESULTS: Mucosal extension was predominant in papillary and nodular tumors, but
      submucosal extension was predominant in diffusely infiltrating and nodular
      infiltrating tumors. Submucosal extension usually consisted of direct or
      lymphatic invasion. The mean length of submucosal extension was 6.0 mm.
      Superficial spread of cancer, defined as mucosal extension of more than 20 mm
      from the main lesion, was seen in 8 specimens. No patient had an anastomotic
      recurrence when the tumor-free resection margin was greater than 5 mm.
      CONCLUSIONS: The pattern of infiltration at the proximal border of resected hilar
      bile duct carcinomas is closely related to the gross tumor type. The length of
      submucosal extension is usually less than 10 mm. Superficial spread of cancer is
      seen in more than 10% of cases. A tumor-free proximal resection margin of 5 mm
      appears to be adequate in hilar bile duct carcinoma.

PMID- 9527065
TI  - Primary sclerosing cholangitis: resect, dilate, or transplant?
AB  - OBJECTIVE: The current study examines the results of extrahepatic biliary
      resection, nonoperative endoscopic biliary dilation with or without percutaneous
      stenting, and liver transplantation in the management of patients with primary
      sclerosing cholangitis (PSC). SUMMARY BACKGROUND DATA: Primary sclerosing
      cholangitis is a progressive inflammatory disease leading to secondary biliary
      cirrhosis. The most effective management of sclerosing cholangitis before the
      onset of cirrhosis remains unclear. METHODS: From 1980 to 1994, 146 patients with
      PSC were managed with either resection of the extrahepatic bile ducts and long
      term transhepatic stenting (50 patients), nonoperative endoscopic biliary
      dilation with or without percutaneous stenting (54 patients), medical therapy (28
      patients), and/or liver transplantation (21 patients). RESULTS: Procedure-related
      morbidity and mortality rates were similar between surgically resected and
      nonoperatively managed patients. In noncirrhotic patients, the serum bilirubin
      level was significantly (p < 0.05) reduced from preoperative levels (8.3+/-1.5
      mg/dL) 1 (1.7+/-0.4 mg/dL) and 3 (2.7+/-0.9 mg/ dL) years after resection, but
      not after endoscopic or percutaneous management. For noncirrhotic PSC patients,
      overall 5-year survival (85% vs. 59%) and survival until death or transplantation
      (82% vs. 46%) were significantly longer (p < 0.05) after resection than after
      nonoperative dilation with or without stenting. For cirrhotic patients, survival
      after liver transplantation was longer than after resection or nonoperative
      dilation with or without stenting. Five patients developed cholangiocarcinoma,
      including three (6%) of the nonoperatively managed patients but none of the
      resected patients. CONCLUSIONS: In carefully selected noncirrhotic patients with
      PSC, resection and long-term stenting remains a good option. Patients with
      cirrhosis should undergo liver transplantation.

PMID- 9527066
TI  - Survival and recurrence after liver transplantation versus liver resection for
      hepatocellular carcinoma: a retrospective analysis.
AB  - OBJECTIVE: This study compares the results of liver transplantation (LTx) and
      liver resection (LR) for hepatocellular carcinoma (HCC) to test the widespread
      hypothesis that LTx is the preferable approach for small HCCs. SUMMARY BACKGROUND
      DATA: With respect to scarcity of donor organs and poor results, LTxs for large
      HCCs are obsolete. Small HCC transplantations have been reported to result in an
      excellent survival rate. However, the data of comparative studies are
      controversial. METHODS: Patients who were treated curatively by LTx (n = 50) or
      LR (n = 52) for HCC were included in this retrospective study. Survival and
      freedom from recurrence were analyzed. Patients were stratified according to
      prognostic factors (pT classification, tumor size, number of tumor nodules,
      vascular infiltration, and cirrhosis). RESULTS: Overall, after LTx and LR the 3
      year survival rate and recurrence rate were not significantly different. In the
      Cox analysis, tumor size (p = 0.02) and vascular infiltration (p = 0.04) were
      independent variables after LTx, whereas after LR, none of the tested prognostic
      parameters was significant. With regards to recurrence, tumor size was the only
      independent factor, after both LTx and LR (p = 0.02, respectively). Directly
      comparing the two therapeutic approaches, a 3-year survival rate in pT 1/2,
      oligocentric (1-5 nodules), and oligocentric and small tumors proved to be
      superior after LTx. The recurrence rate after LTx was superior to LR in pT 1/2
      and oligocentric tumors. Remarkably, for small (< or = 5 cm) tumors, LTx and LR
      resulted in a similar 3-year survival rate and freedom from recurrence.
      CONCLUSIONS: According to our analysis, the oncological advantage of LTx compared
      with LR is questionable. This applies especially for small tumors. Superior
      results of LTx in early stage HCC and particularly in oligocentric tumors may be
      attributed to incorrect preoperative diagnosis. Nevertheless, LTx is a reasonable
      treatment for patients with early stage tumors if a LR is impossible because of
      tumor localization or poor functional hepatic capacity.

PMID- 9527068
TI  - Liver transplantation complicated by misplaced TIPS in the portal vein.
AB  - OBJECTIVE: The purpose of this study was to determine the incidence and
      complications related to transjugular intrahepatic portosystemic shunt (TIPS)
      stents found in the portal vein at the time of an orthotopic liver
      transplantation. BACKGROUND: Transjugular intrahepatic portosystemic shunts are
      frequently used in patients with end-stage liver disease as a bridge to liver
      transplantation. The incidence of finding the metal stent outside of the liver
      parenchyma at the time of transplantation is reported as high as 30%. Most cases
      that have been detailed involve stents misplaced in the vena cava with various
      outcomes. Almost no data are available regarding stents misplaced into the portal
      vein. METHODS AND RESULTS: We report our experience with four patients with whom
      a TIPS stent was found misplaced in the portal vein at the time of liver
      transplantation, including one patient with a stent extending into the superior
      mesenteric vein. This patient required extensive venous reconstruction using a
      retropancreatic "pant" donor-iliac vein graft. The three other patients were
      transplanted without the need for extensive venous reconstruction. There was no
      significant difference in operative times for this group of patients, but there
      was a significant increase in the requirement for blood transfusion. In a follow
      up period ranging from 6 months to 2 years, all patients remained alive and had
      normal portal venous flow and functioning allografts. Most misplaced stents were
      placed in patients with small cirrhotic livers and by radiologists with minimal
      experience with the procedure. CONCLUSIONS: Misplaced TIPS in the portal vein
      before liver transplantation is a more frequent complication than previously
      reported; however, it does not represent major technical difficulty if a clamp
      can be placed proximally on the portal vein. In the case of a stent extending
      below the spleno-mesenteric confluence, interposition grafts such as a donor
      iliac vein graft are necessary for venous reconstruction. The experience of the
      radiologist is critical to prevent this complication.

PMID- 9527067
TI  - Surgical intervention for patients with stage IV-A hepatocellular carcinoma
      without lymph node metastasis: proposal as a standard therapy.
AB  - OBJECTIVE: The aim of this study was to evaluate the effects of surgical
      treatments for patients with stage IV-A hepatocellular carcinoma (HCC) without
      lymph node metastasis. SUMMARY BACKGROUND DATA: Nonsurgical therapy for highly
      advanced HCC patients has yielded poor long-term survival. Surgical intervention
      has been initiated in an effort to improve survival. METHODS: The outcome of 150
      patients who underwent hepatic resection was studied. Survival analysis was made
      by stratifying stage IV-A HCC patients into two groups-those with and those
      without involvement of a major branch of the portal or hepatic veins. Those with
      involvement were further divided into subgroups according to major vascular
      invasions. RESULTS: Patients who had multiple tumors in more than one lobe
      without vascular invasion had a significantly better 5-year survival rate (20%)
      than those with vascular invasion (8%) (p < 0.01). The survival rate of patients
      with hepatic vein tumor thrombi (10%) was better than the rate for those with
      tumor thrombi in the inferior vena cava (0%), in whom no patients survived more
      than 2 years, although the survival rate for those with portal vein tumor thrombi
      in the first branch (11%) was no different from the rate for that in the portal
      trunk (4%). The operative mortality decreased from 14.3% in the first 6 years to
      1.4% in the following 5 years. CONCLUSIONS: Surgical intervention for stage IV-A
      HCC patients brought longer survival rates for some patients. We recommend
      surgical intervention as an effective therapeutic modality for patients with
      advanced HCC.

PMID- 9527069
TI  - Improved airway healing using basic fibroblast growth factor in a canine tracheal
      autotransplantation model.
AB  - OBJECTIVE: We studied 22 dogs to examine the effect of basic fibroblast growth
      factor (bFGF) alone, in comparison with omental or muscular wrapping on airway
      healing in a tracheal autotransplantation model. SUMMARY BACKGROUND DATA: Basic
      fibroblast growth factor is one of the most potent promoters of angiogenesis and
      has an ability to enhance blood supply to the ischemic airway. Topical
      administration of a fibrin glue enriched with 5 microg/cm2 bFGF, determined as a
      proportion of surface area of the tracheal grafts, improved revascularization of
      orthotopic canine tracheal autografts in a previous study. METHODS: All animals
      received orthotopic tracheal transplantation using 6-ring autografts that
      occupied a distal part of the thoracic trachea. Twenty-two animals were
      classified randomly into the following four groups: no treatment (Group G1, n =
      4), muscular wrapping (Group G2, n = 4), omental wrapping (Group G3, n = 4), and
      topical administration of fibrin glue enriched with 5 microg/cm2 bFGF (Group G4,
      n = 10). Autografts were harvested 60 days after transplantation and assessed by
      the percent patency and histology. RESULTS: Devascularized tracheal autografts
      could not maintain their structural integrity without other treatments (Group
      G1). In contrast, more than half of all autografts receiving treatments remained
      viable, as demonstrated by gross and histologic findings (Groups G2, G3, and G4).
      Treatments with bFGF and omentum showed significantly better graft viability than
      no treatment. However, there was no statistical difference in the viability of
      tracheal autografts among the three treatment groups. In terms of the time
      performance ratio, bFGF was the best treatment for the devascularized autografts.
      CONCLUSIONS: Topical administration of bFGF was superior to the omental or
      muscular wrapping in terms of the time performance ratio. Clinical trials will be
      necessary to determine whether these findings are applicable to humans.

PMID- 9527070
TI  - Results of omental flap transposition for deep sternal wound infection after
      cardiovascular surgery.
AB  - OBJECTIVE: Our experience with omental flap transposition in the treatment of
      deep sternal wound infections is reviewed here with an emphasis on efficacy, risk
      factors for in-hospital mortality rates, and long-term results. SUMMARY
      BACKGROUND DATA: Even with improvements in muscle and omental flap transposition,
      the timing of closure and the surgical strategy are controversial. METHODS: Forty
      four consecutive patients with deep sternal wound infections were treated using
      the omental flap transposition from 1985 through 1994. The strategies included
      debridement with delayed omental flap transposition or single-stage management,
      which consisted of debridement of the sternal wound and omental flap
      transposition. Methicillin-resistant Staphylococcus aureus was cultured from more
      than 50% of the wounds. A logistic regression analysis was used to identify the
      predictors of in-hospital death after omental flap transposition. RESULTS: There
      were seven (16%) in-hospital deaths. Univariate analysis demonstrated that
      hemodialysis and ventilatory support at the time of omental flap transposition
      were significantly associated with in-hospital mortality rates (p = 0.0023 and p
      = 0.0075, respectively). Thirty-seven patients whose wounds healed well were
      discharged from the hospital. Two patients with cultures positive for methicillin
      resistant Staphylococcus aureus had recurrent sternal infections. Patients
      without positive methicillin-resistant Staphylococcus aureus cultures had good
      long-term results after reconstructive surgery. CONCLUSIONS: Transposition of an
      omental flap is a reliable option in the treatment of deep sternal wound
      infections, unless the patients require ventilatory support or hemodialysis at
      the time of transposition.

PMID- 9527071
TI  - Abnormal coronary flow in infarct arteries 1 year after myocardial infarction is
      predicted at 4 weeks by corrected Thrombolysis in Myocardial Infarction (TIMI)
      frame count and stenosis severity.
AB  - Because 24% to 30% of patent infarct-related arteries occlude in the year
      following thrombolytic therapy for acute myocardial infarction, angiographic
      factors including corrected Thrombolysis in Myocardial Infarction (TIMI) frame
      count which may predict abnormal infarct-artery flow, require definition. We
      examined changes in coronary flow and infarct-artery lesion severity by
      computerized quantitative angiography over 1 year in 154 patients with a patent
      infarct-related artery 4 weeks after myocardial infarction. These patients were
      randomized to receive either ongoing daily therapy of 50 mg aspirin and 400 mg
      dipyridamole, or placebo. All angiograms were interpreted blind in our core
      angiographic laboratory. Infarct-artery flow, assessed by corrected TIMI frame
      counts, was normal (< or = 27) in 46% and 45% of patients at 4 weeks and 1 year,
      respectively. At 4 weeks, patients with corrected TIMI frame counts < or = 27 had
      higher ejection fractions (60+/-11% vs 56+/-12%; p = 0.04) than those with
      corrected TIMI frame counts >27. On multivariate analysis, corrected TIMI frame
      count and stenosis severity were predictive of late abnormal infarct-artery flow
      (TIMI 0 to 2 flow, both p <0.01). Only stenosis severity at 4 weeks predicted
      reocclusion at 1 year (p <0.0001). Aspirin and dipyridamole had no effect on flow
      or reocclusion. Thus, corrected TIMI frame count and stenosis severity at 4 weeks
      was highly correlated with infarct-artery flow at 1 year.

PMID- 9527072
TI  - Activation of coagulation and fibrinolysis after rehabilitative exercise in
      patients with coronary artery disease.
AB  - It has been suggested that blood coagulation be activated and fibrinolytic
      activity be impaired in patients with coronary artery disease (CAD). With regard
      to the activation of coagulation and fibrinolysis occurring during exercise in
      healthy individuals, we examined the hypothesis that rehabilitative exercise in
      patients with CAD might give rise to an exaggerated activation of coagulation. In
      12 patients with angiographically documented CAD without myocardial infarction
      within the preceding 6 months (male, age 55+/-9 years [SD]) and in 12 healthy
      controls (male, 52+/-7 years), molecular markers of thrombin, fibrin, and plasmin
      formation were determined before and after a rehabilitative group exercise
      session lasting 1 hour. Resting levels of prothrombin fragment 1+2 were lower in
      patients with CAD (0.67+/-0.2 [SE] vs 1.04+/-0.2 nmol/L, p <0.001) and remained
      unchanged after exercise, whereas a significant increase was noted in controls (p
      <0.01). After exercise, plasma levels of thrombin-antithrombin III complexes and
      of fibrinopeptide A increased significantly in both groups, although there were
      more pronounced changes in controls. Exercise resulted in a marked generation of
      plasmin as indicated by plasmin-alpha2-antiplasmin complexes increasing 2.5-fold
      in patients (p <0.001) and threefold in controls (p <0.001). Repeated experiments
      in control subjects after administration of aspirin (day 1: 500 mg; days 2 to 5:
      100 mg) documented that differences between groups could not be attributed to
      aspirin medication (100 mg/day) in patients with CAD. We concluded that
      rehabilitative exercise in patients with CAD beyond the immediate postinfarction
      period has no detrimental effects on thrombin, fibrin, and plasmin formation.

PMID- 9527073
TI  - Effects of prior aspirin and anti-ischemic therapy on outcome of patients with
      unstable angina. TIMI 7 Investigators. Thrombin Inhibition in Myocardial
      Ischemia.
AB  - Both aspirin and beta-adrenergic blocking drugs have been shown to reduce the
      risk of death or acute myocardial infarction (AMI) in patients with unstable
      angina, but their effect during chronic use on the presentation of acute coronary
      syndromes is less well defined. Calcium antagonists and oral nitrates are also
      widely prescribed for patients with coronary disease, but their effect on
      presentation of acute myocardial ischemia is unknown. We retrospectively examined
      the effects of prior aspirin and anti-ischemic medical therapy on clinical events
      in 410 patients hospitalized for unstable angina. Ischemic pain occurred at rest
      for a duration of 5 to 60 minutes. During hospitalization, 97% of patients
      received aspirin and all received the direct thrombin inhibitor bivalirudin for
      at least 72 hours. Despite being older and more likely to have risk factors for
      coronary disease and poor outcome, patients receiving aspirin before admission
      were less likely to present with non-Q-wave AMI (5% vs 14% in patients not on
      aspirin, p = 0.004). Prior beta blocker, calcium antagonist, or nitrate
      administration did not appear to modify presentation as unstable angina or non-Q
      wave AMI. In a multivariate model, the combined incidence of death, AMI not
      present at enrollment, or recurrent angina was best predicted by age (adjusted
      odds ratio [95% confidence interval] 2.38 [1.14 to 3.98]) and presence of
      electrocardiographic changes with pain on presentation (adjusted odds ratio 2.83
      [1.50 to 5.35]) but was not related to prior or in-hospital medical therapy.
      Thus, aspirin but not anti-ischemic therapy before hospitalization of patients
      with unstable angina was associated with a decreased incidence of non-Q-wave AMI
      on admission.

PMID- 9527074
TI  - Comparison of exercise electron beam computed tomography and sestamibi in the
      evaluation of coronary artery disease.
AB  - This blinded, single center study prospectively compares exercise electron beam
      computed tomography (EBCT) with stress technetium-99m (Tc-99m) sestamibi single
      photon emission computed tomography (SPECT) in 33 patients undergoing coronary
      angiography for evaluation of chest pain. Patients undergoing routine cardiac
      catheterization for the diagnosis of chest pain were imaged at rest using EBCT.
      Patients exercised on a semi-supine ergometer, and exercise EBCT was immediately
      followed by injection of Tc-99m sestamibi for assessment of myocardial ischemia.
      At peak exercise, Tc-99m SPECT, followed immediately by nonionic contrast
      material, was injected intravenously to directly compare these 2 imaging
      techniques. Patients were reimaged with Tc-99m SPECT at rest 24 to 48 hours after
      stress. Exercise EBCT, which was analyzed using a global ejection fraction
      measure, had a sensitivity of 81% and a specificity of 76%, compared with
      angiography. Using the development of a new regional wall motion abnormality as
      evidence of obstructive coronary artery disease (CAD), EBCT yielded a specificity
      of 100% and a sensitivity of 88%. Reversible perfusion defects identified by
      SPECT, as evidence of obstructive CAD, revealed a sensitivity of 75% and a
      specificity of 71%. The specificity of regional wall motion analysis by EBCT was
      significantly better than SPECT (p <0.01) in this population. This study
      demonstrates regional wall motion assessed by EBCT to be as sensitive and more
      specific than SPECT myocardial perfusion imaging in identifying obstructive CAD
      as defined by angiography.

PMID- 9527075
TI  - Ergonovine-induced alterations in coronary flow velocity preceding onset of
      occlusive spasm in patients without significant coronary artery stenoses.
AB  - This study examined serial changes in coronary flow velocity to elucidate the
      dynamic change of coronary circulation during coronary spasm. Twenty patients
      with variant angina and 27 control patients were studied. Coronary flow velocity
      was monitored using a Doppler guidewire following intracoronary ergonovine
      administration. In the control group, diastolic flow velocity either did not
      change or increased slightly in response to ergonovine. However, in patients with
      variant angina, 2 patterns of flow velocity alterations were observed. In the
      first pattern, flow initially increased and then suddenly decreased (16 of 20
      patients). In the second pattern, flow gradually decreased (3 of 20 patients). In
      the remaining patient, the coronary flow alteration could not be detected because
      of branch spasm. When abnormally high flow velocity was defined as a 100%
      increase in flow after ergonovine administration within 1 minute, and abnormally
      low flow velocity was defined as a 50% decrease in flow to diagnose variant
      angina, sensitivities of 35%, 75%, and 85% were noted if flow was measured 1.0,
      2.0, and 3.0 minutes after ergonovine administration, respectively. These
      abnormal flow velocities were observed before ischemic ST changes appeared. In
      conclusion, in patients with variant angina, characteristic serial changes in
      coronary flow velocity occur before occlusive spasm. Variant angina may be
      diagnosed earlier by monitoring flow velocity rather than by monitoring for
      ischemic electrocardiographic changes.

PMID- 9527076
TI  - Dispersions of the QT interval in postmyocardial infarction patients presenting
      with ventricular tachycardia or with ventricular fibrillation.
AB  - Increased QT interval dispersion is associated with ventricular arrhythmias. The
      aim of this study was to examine if in postmyocardial infarction patients with
      impaired left ventricular function, increased QT dispersion is associated with
      ventricular tachycardia (VT) and ventricular fibrillation (VF). Measures of QT
      dispersion, calculated as maximum-minimum (D) and standard deviation (SD) of
      QTend, QTapex, JTend, JTapex, and Tend intervals in the 12-lead
      electrocardiogram, were compared in patients who late after myocardial infarction
      experienced sustained VT (VT group) only, VF (VF group) only, or had no
      ventricular arrhythmias (controls). The 25 patients in each group were
      individually matched for age, gender, number of diseased coronary vessels,
      location of the previous myocardial infarction, and left ventricular ejection
      fraction. Dispersion measures of QTend, QTapex, and JTapex intervals separated VT
      group from controls, but none of the measures separated the VF group from
      controls. QTendD was 49+/-18 ms in controls, 57+/-18 ms in the VF group (controls
      vs VF group, p = NS), and 65+/-29 ms in the VT group (controls vs VT group, p
      <0.05). VT group had increased QTapexSD, JTapexSD, and JTapexD compared with the
      VF group. The cycle length of induced sustained monomorphic VT, present in 19 VT
      and 19 VF patients, correlated with several dispersion indexes in the VT group,
      but not with those in the VF group. Thus, in postmyocardial infarction patients
      with a severely damaged left ventricle, increased QT dispersion is associated
      with susceptibility to sustained VT, but not to VF.

PMID- 9527077
TI  - Usefulness of enhanced insulin secretion during an oral glucose tolerance test as
      a predictor of restenosis after direct percutaneous transluminal coronary
      angioplasty during acute myocardial infarction in patients without diabetes
      mellitus.
AB  - To determine predictive factors of the development of restenosis after
      percutaneous transluminal coronary angioplasty (PTCA), 25 nondiabetic nonobese
      patients aged <80 years old and 57 consecutive patients with successful direct
      PTCA with acute myocardial infarction were subjected to a 75-g oral glucose
      tolerance test (OGTT) and underwent follow-up coronary angiography 4 months
      later. The relation between the development of restenosis (late loss index: the
      decrease in the absolute minimal lumen diameter [MLD] at follow-up coronary
      angiography divided by MLD measured 1 day after PTCA) and the results of OGTT
      together with basic patient characteristics like age, body mass index, plasma
      levels of cholesterol, triglycerides, and high-density lipoprotein cholesterol
      were analyzed. Spearman's rank correlation analysis revealed that neither age,
      body mass index, nor plasma lipids correlated with late loss index, but only
      insulin area (p = 0.041) and insulin area/glucose area (p = 0.038) significantly
      correlated with the development of restenosis; a stepwise multiple regression
      analysis revealed that the insulin area was the only independent predictor of
      restenosis (p = 0.019). These results suggest that enhanced insulin secretion in
      response to glucose plays an important role in the development of restenosis
      after direct PTCA in non-diabetic patients, which may be through the direct
      action of insulin on smooth muscle cells of the coronary artery. This study also
      suggests the importance of performing OGTT for patients undergoing PTCA for the
      prediction of the development of restenosis.

PMID- 9527078
TI  - Frequency, predictors, and appropriateness of blood transfusion after
      percutaneous coronary interventions.
AB  - Increased awareness of the risks of blood-borne infections has recently led to
      profound changes in the practice of transfusion medicine. These changes include,
      among others, the development of guidelines by the American College of Physicians
      (ACP) for transfusion. Although the incidence and predictors of vascular
      complications of percutaneous interventions have been well defined, there are
      currently no data on frequency, risk factors, and appropriateness of blood
      transfusions. We performed a retrospective analysis of 628 consecutive
      percutaneous coronary revascularization procedures. Predictors of blood
      transfusion were identified using multivariate logistic regression analysis.
      Appropriateness of transfusions was determined using modified ACP guidelines.
      Transfusions were administered after 8.9% of interventions (56 of 628).
      Multivariate analysis identified age >70 years, female gender, procedure
      duration, coronary stenting, acute myocardial infarction, postprocedural use of
      heparin and intra-aortic balloon pump placement as independent predictors of
      blood transfusions (all p <0.05). According to the ACP guidelines, 36 of 56
      patients (64%) received transfusions inappropriately. Transfusion reactions
      (fever) occurred in 10% of patients who received tranfusions appropriately and in
      5% of patients who received tranfusions inappropriately. The estimated additional
      costs per procedure related to transfusions were $551 and $419, respectively. In
      conclusion, unnecessary transfusions were performed frequently after percutaneous
      coronary interventions. Application of available guidelines could reduce the
      number of unnecessary transfusions, thus avoiding exposure of patients to
      additional risks and reducing procedural costs.

PMID- 9527079
TI  - Comparison of aggressive versus nonaggressive balloon dilatation for stent
      deployment on late loss and restenosis in native coronary arteries.
AB  - Aggressive balloon dilatation is currently performed to assure full stent
      expansion and minimize the risk of stent thrombosis. It is not known if
      aggressive stent expansion leads to further increases in intimal proliferation
      and restenosis. A retrospective analysis was performed of 688 consecutive
      coronary narrowings in which stents were implanted. Angiographic follow-up was
      performed and quantitative coronary angiographic measurements were obtained using
      electronic calipers. Patients were divided into 2 groups. Group A (212
      narrowings) had stents implanted before 1993, before the routine use of
      aggressive stent expansion techniques. Group B (476 narrowings) had stents
      implanted after 1993, when oversized balloons or high-pressure inflations were
      performed inside stents. Comparisons were made between angiographic changes and
      clinical outcomes between the 2 groups. Group B lesions had less favorable
      characteristics due to longer lengths of lesions. Despite this there was less
      angiographic and clinical restenosis in this cohort. There was no difference in
      late loss between the 2 groups. Thus, aggressive stent implantation techniques
      were not associated with increased late loss or restenosis.

PMID- 9527080
TI  - Frequency of adverse clinical events in the 12 months following successful
      intracoronary stent placement in patients treated with aspirin and ticlopidine
      (without warfarin).
AB  - Little is known about the frequency of adverse events in the year following stent
      placement in patients treated with aspirin and ticlopidine, without warfarin. We
      analyzed the first such 234 consecutive patients treated at our hospital between
      October 1994 and December 1995. Their mean age was 62+/-12 years; 40% had had a
      prior myocardial infarction, 22% had undergone coronary artery bypass surgery,
      and 65% had multivessel disease. The indication for stent placement was
      dissection or abrupt closure in 24% of patients and suboptimal balloon
      angioplasty results in 14%; placement was elective in 62% of patients. Three
      hundred forty-five coronary segments were treated in the 234 patients; 305 stents
      (1.3 stents/patient) were placed. Palmaz-Schatz coronary stents (75%), Gianturco
      Roubin stents (21%), and Johnson & Johnson biliary stents (4%) were used. Mean
      nominal stent size was 3.4+/-0.4 mm. High-pressure inflations (> or = 14 atm,
      mean 17+/-2) were performed in all patients. The mean residual stenosis was 3+/
      5% by visual estimate. Intravascular ultrasound was utilized to facilitate stent
      placement in 53% of patients. Mean follow-up was 1.6+/-0.5 years. There were no
      deaths, Q-wave myocardial infarctions, coronary artery bypass operations, or
      repeat angioplasty procedures required during the remainder of the
      hospitalization or in 30 days after stent placement; stent thrombosis did not
      occur. Kaplan-Meier analysis of adverse events in the 6 months following the
      procedure revealed a mortality rate of 0.9%; the rate of myocardial infarction (Q
      wave or non-Q-wave) was 1.3%. Bypass surgery was performed in 0.9% and
      angioplasty for in-stent restenosis was performed in 9.5% of patients. Any 1 of
      these events occurred in 11.7% of patients in the 6 months after the procedure.
      The corresponding event rates at 1 year were 1.3%, 2.2%, 3.5%, and 12.2%,
      respectively; any 1 of these events occurred in 16.5% of patients. In patients
      receiving intracoronary stents of varying designs followed by high-pressure
      postdeployment inflations in whom an excellent visual angiographic result is
      achieved, antithrombotic therapy with aspirin and ticlopidine is associated with
      a very low frequency of adverse cardiovascular events in the 12 months following
      the procedure regardless of the indication for stent placement.

PMID- 9527081
TI  - Design of a randomized, placebo-controlled multicenter trial on the long-term
      effects of intermittent transdermal nitroglycerin on left ventricular remodeling
      after acute myocardial infarction. Transdermal Nitroglycerin Investigators Group.
AB  - Nitrates are widely used in the treatment of patients with ischemic heart disease
      and in those with angina following acute myocardial infarction. Short-term
      studies indicate that the administration of nitrates may prevent left ventricular
      (LV) dilation and infarct expansion. Animal models suggest that prolonged
      nitroglycerin use after infarction may limit LV remodeling similar to that
      observed with angiotensin-converting enzyme inhibitors. However, to date there
      have been no trials evaluating the effects of nitrates on LV volumes in patients
      surviving acute myocardial infarction. We therefore performed a randomized double
      blind, placebo-controlled trial designed to investigate the long-term (6 month)
      efficacy of intermittent transdermal nitroglycerin patches on LV remodeling in
      291 survivors of acute myocardial infarction. Patients were randomized to receive
      either placebo or a nitroglycerin patch that delivered 0.4, 0.8, or 1.6 mg/hour.
      Gated radionuclide angiography was used to assess serial changes in LV ejection
      and cardiac volumes. The baseline characteristics of the study population were
      similar in all 4 treatment groups. The study protocol and the main design-related
      issues are described.

PMID- 9527082
TI  - Cardiac denervation after radiofrequency ablation of supraventricular
      tachycardias.
AB  - Inappropriate sinus tachycardia and atrial arrhythmias have been reported after
      radiofrequency ablation. Previous studies have suggested that cardiac denervation
      is a possible explanation for these rhythm disturbances. The aim of this study
      was to investigate possible alterations in autonomic innervation of the heart
      after ablation using the techniques of heart rate variability (HRV) analysis and
      metaiodobenzylguanidine (I-123 MIBG) scintigraphy. The subjects of this study
      were 30 consecutive patients aged 25 to 40 years, without structural heart
      disease, who underwent radiofrequency ablation of atrioventricular nodal slow
      pathways, and posteroseptal and left lateral accessory pathways because of
      symptomatic recurrent reentrant tachycardias. Time and frequency domain analysis
      of HRV after ablation revealed a significant reduction in the indexes of the mean
      of all 5-minute standard deviation of RR intervals (p = 0.042), low frequency (p
      = 0.0005), and total frequency (p = 0.008) compared with preablation values in
      the group of patients who underwent atrioventricular nodal slow pathway ablation.
      Patients who underwent ablation of a posteroseptal accessory pathway also had
      significant attenuation of the indexes of standard deviation about the mean RR
      interval (p = 0.03), standard deviation of 5-minute mean RR intervals (p =
      0.006), and low-frequency (p <0.0001), and high-frequency (p <0.0001) components.
      Significant I-123 MIBG map defects, indicating efferent cardiac sympathetic
      denervation, were also found in the same groups of patients: atrioventricular
      nodal group (p = 0.0024), posteroseptal accessory pathway group (p = 0.0007).
      None of the above changes in HRV and 123-I MIBG scintigraphy were seen in
      patients who underwent ablation of left lateral accessory pathways. We conclude
      that radiofrequency ablation in the anterior, mid-, and posterior regions of the
      low intraatrial septum may disrupt sympathetic fibers located in these regions,
      causing cardiac sympathetic denervation. The density of these fibers appear to be
      less along the left atrioventricular groove.

PMID- 9527083
TI  - Effects of moderate intensity exercise on serum lipids in African-American men
      with severe systemic hypertension.
AB  - The prevalence of systemic hypertension and its cardiovascular consequences is
      higher in African-Americans than in whites. Low to moderate intensity aerobic
      exercise lowers blood pressure (BP) in African-American patients with severe
      hypertension. It is not known whether such exercise can improve lipid metabolism
      in these patients. Thirty-six African-American men with established essential
      hypertension, aged 35 to 76 years, were randomly assigned to an exercise (n = 17)
      or no exercise (n = 19) group. The exercise group exercised for 16 weeks, 3
      times/week, at 60% to 80% of maximum heart rate. After 16 weeks, peak oxygen
      uptake in the exercise group improved (21+/-4 vs 23+/-3 ml/kg/min; p <0.001).
      Body weight did not change. Exercise intensity correlated with high-density
      lipoprotein (HDL) cholesterol changes from baseline to 16 weeks (r = 0.65; p
      <0.01) and was the strongest predictor of these changes (R2 = 0.4; p = 0.009).
      Lipoprotein-lipid changes in the 2 randomized groups did not differ
      significantly. A 10% increase in HDL cholesterol--42+/-19 versus 46+/-19 mg/dl; p
      = 0.003--noted in 10 patients who exercised > or = 75% of maximal heart rate
      suggested the existence of an exercise intensity threshold. Thus low to moderate
      intensity aerobic exercise may not be adequate to modify lipid profiles favorably
      in patients with severe hypertension. However, substantial changes in HDL
      cholesterol were noted in patients exercising at intensities > or = 75% of age
      predicted maximum heart rate, suggesting an exercise-intensity threshold.

PMID- 9527084
TI  - Long-term follow-up of St. Jude Medical prosthesis in a young rheumatic
      population using low-level warfarin anticoagulation: an analysis of the temporal
      distribution of causes of death.
AB  - This study assesses the long-term (mean 52+/-24 months) performance of the St.
      Jude Medical (SJM) valve in 200 young (mean age 31+/-13 years) rheumatic patients
      on low-level warfarin anticoagulation combined with dipyridamole. Follow-up was
      95% complete and comprised 867 patient-years. There were 33 deaths (3.8%/patient
      year). Death was valve related in 12 cases and due to left ventricular
      dysfunction in 10. Death due to left ventricular dysfunction occurred earlier
      after surgery than death due to other causes (10+/-7 vs 29+/-18 months, p
      <0.005); these patients had larger preoperative left ventricular dimensions than
      the rest of the group (end-systolic diameter 51+/-13 vs 37+/-16 mm, end-diastolic
      diameter 66+/-13 vs 50+/-19 mm, p = 0.006). Actuarial probability of survival was
      81% at 86 months and probability of event-free survival was 71%. The median
      international normalized ratio was 1.88+/-0.54. Thromboembolism (13 events)
      occurred at a linearized rate of 1.5%/patient-year. There were 11 major bleeding
      episodes (1.3%/patient-year), 4 cases of prosthetic valve endocarditis
      (0.8%/patient-year), and 12 paraprosthetic leaks (1.4%/patient-year). No valve
      obstructions or reoperations occurred. Thus, the SJM valve performs well on low
      level anticoagulation combined with dipyridamole. Left ventricular dysfunction
      was a common cause of death in the early postoperative period.

PMID- 9527085
TI  - Intravascular ultrasonic characteristics and vasoreactivity of the pulmonary
      vasculature in children with pulmonary hypertension.
AB  - We sought to describe the morphologic characteristics of pulmonary arteries by
      intravascular ultrasound (IVUS) in children with and without pulmonary
      hypertension to compare these anatomic findings with those of pulmonary wedge
      angiography, and to determine the relation between these structural findings and
      functional reactivity to pulmonary vasodilators. Direct evaluation of pulmonary
      vascular structure in children with pulmonary hypertension with current imaging
      techniques has been limited and little is known about the relation between
      structural and functional characteristics of the pulmonary vasculature. In 23
      children undergoing cardiac catheterization (15 with pulmonary hypertension and 8
      controls) we performed IVUS and pulmonary wedge angiography of the distal
      pulmonary arteries in the same lobe. IVUS was performed in 44 pulmonary arteries
      measuring 2.5 to 5.0 mm internal diameter with a 3.5Fr 30-MHz IVUS catheter. We
      assessed vasoreactivity to inhaled nitric oxide (NO) and oxygen in 13 of 15
      children with pulmonary hypertension. Baseline pulmonary vascular resistance
      (PVR) was greater in the 15 children with pulmonary hypertension than in the 8
      controls (9.5+/-1.9 vs 1.5+/-0.3 U x m2, p <0.05). NO lowered PVR in patients
      with pulmonary hypertension (p <0.05). IVUS studies in patients with pulmonary
      hypertension showed a thicker middle layer, wall thickness ratio, and diminished
      pulsatility than did those in controls (p <0.05). The inner layer was not
      visualized by IVUS in any control patient, but was seen in 9 of 15 patients with
      pulmonary hypertension. Pulmonary artery wedge angiography correlated with
      baseline mean pulmonary artery pressure and PVR as well as with IVUS findings of
      wall thickness ratio and inner layer thickness. The inner layer was not
      visualized by IVUS in any patient with grade 1 wedge angiograms or in 86% of
      patients with grade 2 wedge angiograms. All patients with grade 4 and 80% of
      patients with grade 3 wedge angiograms had a visible inner layer. Vasoreactivity
      to NO and oxygen did not correlate with structural assessment of the pulmonary
      vasculature by IVUS. Structural changes in the pulmonary arteries in children
      with pulmonary hypertension can be directly visualized by IVUS, but are not
      predictive of NO-induced pulmonary vasodilation. IVUS examination of pulmonary
      arteries may complement current techniques utilized in the evaluation of children
      with pulmonary hypertension.

PMID- 9527086
TI  - Outcome in cyanotic neonates with Ebstein's anomaly.
AB  - Clinical, angiographic, radiographic, and echocardiographic data on 46 neonates
      with Ebstein's anomaly presenting with cyanosis between 1954 and 1996 were
      reviewed to determine possible risk factors for mortality. Most patients (67%)
      presented at birth with 3 cases diagnosed in utero. Mean systemic oxygen
      saturation was 62+/-12%. An atrial septal defect > or = 4 mm was noted in 20
      patients (44%). The patent right ventricle to pulmonary artery connection was
      present in 10 (22%), and pulmonary atresia was functional in 25 (54%) and
      anatomic in 11 patients (24%). Fifteen patients (35%) underwent surgical
      interventions. Total mortality was 70% (vs 14% in acyanotic patients diagnosed
      during the same time period; p <0.0001) and was related to low cardiac output and
      hypoxia in 20 patients (62%), postoperative complications in 8 (25%), and sudden
      death in 4 (13%). Kaplan-Meier survival estimates were 61% at age 1 week (95%
      confidence interval [CI], 47% to 75%), 48% at age 1 month (95% CI, 34% to 62%),
      and 36% at both 1 and 5 years of age (95% CI, 22% to 50%). Mortality improved
      from 81% in 1954 to 1985 to 47% in 1986 to 1996 (p = 0.04). Significant
      independent predictors of mortality included an atrial septal defect > or = 4 mm
      (odds ratio [OR] 2.39; p = 0.04), reduced left ventricular function (OR 4.10; p =
      0.002), and functional or anatomic pulmonary atresia (OR 2.44, p = 0.003; and OR
      5.97, p = 0.004, respectively). An echocardiographic ratio of the combined right
      atrial and atrialized right ventricular area to the area of the functional right
      ventricle and left heart >1.0 was 100% predictive of mortality.

PMID- 9527087
TI  - Angiotensin-converting enzyme and angiotensinogen gene polymorphisms and heart
      rate variability in twins.
AB  - Decreased heart rate variability (HRV) is associated with congestive heart
      failure, post-myocardial infarction, ventricular arrhythmias, sudden cardiac
      death, and advancing age. A deletion/insertion polymorphism in the angiotensin
      converting enzyme (ACE) gene and a substitution (M235T) in the angiotensinogen
      gene have been associated with risk for heart disease. The aim of this study was
      to determine the heritability of HRV and related parameters in monozygotic and
      dizygotic twins and to assess the influence of ACE and angiotensinogen
      polymorphisms. We studied 95 MZ pairs and 46 DZ pairs. We measured HRV and
      related parameters, ACE and angiotensinogen levels, plasma norepinephrine, ACE,
      and angiotensinogen genotypes. We found that HRV and related parameters were
      significantly influenced by genetic variability, although nonshared genetic
      effects were also important. Angiotensinogen and plasma norepinephrine were
      generally correlated with decreased HRV, whereas ACE was correlated with
      perturbances of normal rhythmic HRV. Nevertheless, the DD ACE genotype was
      associated with increased HRV (p <0.05), whereas angiotensinogen polymorphisms
      had no effect. We conclude that HRV and related parameters are in part heritable.
      Interestingly, the DD ACE genotype is associated with increased HRV.

PMID- 9527088
TI  - Neurohumoral cardiovascular responses to alcohol and their modulation by peroral
      fluid.
AB  - Reports on the physiologic effects of acute alcohol are far from uniform and
      probably reflect differences in study designs, which seldom or never consider the
      effects of coadministered volumes. We therefore measured blood pressure, heart
      rate, and heart rate variability (HRV) by power spectrum analysis, baroreceptor
      sensitivity, arterial blood flow, pulsed-wave velocity (PWV), and plasma levels
      of vasoactive hormones according to 2 protocols: group A = alcohol, 1 g/kg body
      weight, mixed with 500 ml of juice; and group B = similar to A plus 750 ml of
      mineral water. Each group comprised 9 healthy men, studied before and during the
      subsequent 1 and 1/2 hours after finishing the alcohol. In A, but not in B,
      alcohol increased heart rate (p = 0.01) and lowered systolic pressure (p <0.05).
      Plasma renin activity decreased only in B (p <0.01). Atrial natriuretic factor
      decreased in A, but increased in B (both p <0.02). Pancreatic polypeptide
      decreased (both p <0.001), and catecholamines did not change. In both groups,
      alcohol reduced PWV and increased blood flow. Baroreceptor sensitivity and the
      high-frequency band of HRV decreased in both groups. The physiologic response to
      acute administration of alcohol appears to depend on the volume of coadministered
      volumes. Alcohol further appears to interfere with vagal, rather than with
      sympathetic activity.

PMID- 9527090
TI  - Comparison of radial versus brachial approaches for diagnostic coronary
      angiography when the femoral approach is contraindicated.
AB  - One hundred patients with contraindications to the femoral approach were
      randomized to undergo diagnostic coronary angiography via percutaneous radial
      puncture or brachial artery cutdown. Procedure duration, fluoroscopy time, and
      total radiation dose were significantly less via the radial route, whereas
      procedural success, complication rates, and pain scores were comparable; we
      conclude that the radial technique should be the arm approach of choice for new
      trainees, although there will be occasions when radial access fails and a
      brachial approach is required.

PMID- 9527091
TI  - Soluble vascular cell adhesion molecule-1 and E-selectin in patients with acute
      myocardial infarction treated with thrombolytic agents.
AB  - Twenty-three patients enrolled in th GUSTO-III study underwent serial
      measurements of soluble vascular cell adhesion molecule-1 (VCAM-1) and E-selectin
      by enzyme-linked immunosorbent assay at prespecified time intervals. Soluble VCAM
      1, but not E-selectin levels, were increased in patients with acute myocardial
      infarction, indicating that VCAM-1 may serve as a marker of increased endothelial
      activation in acute myocardial infarction.

PMID- 9527089
TI  - Stress myocardial perfusion imaging after coronary angioplasty.
AB  - Stress myocardial perfusion imaging is useful in patient management after
      coronary angioplasty. The ischemic perfusion pattern suggests the presence of
      residual stenosis, restenosis, down stream stenosis, side branch stenosis, and
      remote stenosis.

PMID- 9527092
TI  - Effect of metoprolol in reducing myocardial ischemic threshold during exercise
      and during daily activity.
AB  - In a study of 48 patients with coronary artery disease and evidence of ischemia
      during exercise and daily life, metoprolol reduced the threshold of myocardial
      ischemia in a dose-dependent manner. This effect of beta blockers is probably due
      to increased coronary tone.

PMID- 9527093
TI  - Predicting angiographic narrowing > or = 50% in diameter in each of the three
      major arteries by amounts of calcium detected by electron beam computed
      tomographic scanning in patients with chest pain.
AB  - The evaluation of calcium of the coronary arteries on a vessel-by-vessel basis by
      use of electron beam computed tomography was useful in obstructed coronary
      arteries. The absence of coronary calcification in any vessel was highly specific
      for the absence of an obstructive lesion.

PMID- 9527094
TI  - Comparison of atrial natriuretic peptide versus nitroglycerin for reducing blood
      pressure in acute myocardial infarction.
AB  - In 10 patients with uncomplicated anterior acute myocardial infarction, within 24
      hours after onset, heart rate, plasma renin activity, and the low- to high
      frequency power ratio increased and high-frequency power decreased during
      nitroglycerin infusion; however, both heart rate and plasma renin activity did
      not change, the low- to high-frequency power ratio decreased, and high-frequency
      power increased during atrial natriuretic peptide infusion. Atrial natriuretic
      peptide seems to be more beneficial in its effect on autonomic nervous activity,
      plasma renin activity, and myocardial oxygen consumption than nitroglycerin for
      the treatment of anterior acute myocardial infarction.

PMID- 9527095
TI  - Association between mitral annular calcium and aortic atheroma as detected by
      transesophageal echocardiographic study.
AB  - Significant association was found between the presence of mitral annular calcium
      (MAC) and aortic atheroma detected by transesophageal echocardiography. MAC may
      be an important marker for aortic atherosclerosis.

PMID- 9527096
TI  - Left atrial function is unchanged by implantable defibrillator shocks on hearts
      in sinus rhythm.
AB  - Sixteen patients in sinus rhythm at baseline undergoing implantable cardioverter
      defibrillator implantation were monitored with transesophageal echocardiography
      both before and after direct current cardioversion with currents of 15 to 20 J,
      for any direct current induced atrial dysfunction. We found no change in the
      indexes of atrial function or appearance of spontaneous echo contrast in the
      immediate postshock period by intraoperative transesophageal echocardiography.

PMID- 9527097
TI  - Ventricular late potentials, interstitial fibrosis, and right ventricular
      function in patients with ventricular tachycardia and normal left ventricular
      function.
AB  - We examined 40 patients with ventricular tachycardia (VT) and no evidence of
      heart disease, and found a 50% prevalence of ventricular late potentials (VLPs)
      on the signal-averaged electrocardiogram. This finding was associated with a
      significantly higher content of fibrous tissue on endomyocardial biopsy and a
      lower right ventricular ejection fraction. Thus, VLPs are frequently found in
      idiopathic VT, are a marker for subclinical anatomic and functional abnormalities
      of the right ventricle, and may be associated with a worse outcome.

PMID- 9527098
TI  - Comparison of quantitative Doppler with magnetic resonance imaging for assessment
      of the severity of mitral regurgitation.
AB  - We compared quantitative Doppler echocardiography and cine magnetic resonance
      imaging for calculation of regurgitant volume and regurgitant fraction in mitral
      regurgitation. A good correlation was present between the 2 methods with some
      scatter in patients with severe mitral regurgitation and high regurgitant
      volumes.

PMID- 9527099
TI  - Activation of blood coagulation in patients with mitral stenosis and sinus
      rhythm.
AB  - The aim of this study was to assess whether there is blood coagulation activation
      in patients with mitral stenosis (MS) and sinus rhythm (SR) and to investigate
      the value of left atrial spontaneous echo contrast (LASEC) as a predictive sign
      of increased coagulation activity. Using thrombin-antithrombin III complexes and
      prothrombin fragment 1+2 as in vivo hemostatic markers, we concluded that there
      is a hypercoagulable state in patients with MS and SR when LASEC is present.

PMID- 9527100
TI  - Levels of soluble Fas in patients with myocarditis, heart failure of unknown
      origin, and in healthy volunteers.
AB  - This study showed that serum levels of sFas were elevated in patients with
      myocarditis, and that this elevation was correlated with sIL-2R level as a marker
      of T-cell activation. Therefore, sFas levels may be associated with T-cell
      activation in patients with myocarditis, and elevation of sFas may inhibit
      apoptosis in activated T cells, leading to persistent cell-mediated destruction
      of myocytes in myocarditis.

PMID- 9527101
TI  - Acute hemodynamic effects of metoprolol +/- nitroglycerin in patients with biopsy
      proven lymphocytic myocarditis.
AB  - We evaluated acute hemodynamic effects of metoprolol +/- nitroglycerin in 11
      patients with left ventricular dysfunction and biopsy-proven lymphocytic
      myocarditis. Acute administration of metoprolol improved ejection phase indexes,
      probably through the prolongation of diastole; the addition of a vasodilator
      further enhanced these effects by improving arterial elastance.

PMID- 9527102
TI  - Effects of crystalline nicotinic acid-induced hepatic dysfunction on serum low
      density lipoprotein cholesterol and lecithin cholesteryl acyl transferase.
AB  - Marked lowering of plasma total and low-density lipoprotein cholesterol levels
      that occur during treatment of dyslipidemia with pharmacologic doses of nicotinic
      acid result from hepatotoxicity. Therefore, a marked reduction in low-density
      lipoprotein may suggest generalized liver toxicity and drug treatment should be
      discontinued.

PMID- 9527103
TI  - Left arm/left leg electrocardiographic lead reversal: report of a "natural"
      experiment.

PMID- 9527104
TI  - Nitric oxide contributes to the rise in forearm blood flow during mental stress
      in humans.

PMID- 9527105
TI  - The Clinical Trials Branch at the National Institute on Deafness and Other
      Communication Disorders.

PMID- 9527106
TI  - The multichannel auditory brain stem implant: performance in twenty patients.
AB  - The auditory brain stem implant has been used effectively to provide hearing
      sensations to individuals deafened by bilateral auditory nerve tumors
      (neurofibromatosis type 2). During tumor removal, the auditory brain stem implant
      is implanted into the lateral recess of the fourth ventricle by a
      translabyrinthine approach and is intended to stimulate auditory neurons of the
      cochlear nucleus complex. A new eight-electrode multichannel auditory brain stem
      implant was developed and evaluated in 20 patients who had at least 3 months'
      experience with the device. Mild nonauditory sensations (primarily tingling in
      the head or torso) were encountered in some instances but could be managed by
      changing the stimulus characteristics or excluding electrodes. Testing of
      perceptual performance indicated significant benefit from the device for
      communication purposes, including sound-only sentence recognition scores in three
      patients ranging from 49% to 58% and ability to converse on the telephone. These
      results indicate that significant auditory benefit can be derived from direct
      multichannel electrical stimulation of the auditory portion of the human brain
      stem.

PMID- 9527107
TI  - Tympanic membrane perforations in the diabetic rat: a model of impaired wound
      healing.
AB  - Animal models of type I and type II diabetes mellitus have been studied
      intensively in an effort to define the pathophysiology of the diabetic condition.
      An often-observed clinical manifestation of diabetes is poor wound repair. Thus
      diabetic animals have emerged as useful models for the study of impaired wound
      healing. The healing of acute tympanic membrane (TM) perforations in diabetic
      animals has not been reported. This investigation compares time to closure of a
      standardized TM perforation in rats with streptozotocin-induced diabetes, Zucker
      diabetic fatty rats, and normal control rats. The Zucker diabetic fatty rats
      demonstrate a significantly prolonged time to closure compared with the other two
      groups. This animal model may be useful for future study of TM wound repair.

PMID- 9527108
TI  - Growth of human paragangliomas in the subrenal capsule of the nude mouse.
AB  - Paragangliomas are generally benign, highly vascular, and slowly growing tumors
      of neural crest lineage that occur disproportionately in women. Surgery can
      manage small tumors expeditiously, but extirpation of large tumors is associated
      with morbidity and even mortality. Radiation therapy offers relatively good tumor
      control but also presents development of a secondary malignant neoplasm as a
      possible consequence. Cancer chemotherapeutic agents have been used only in rare
      metastasizing paragangliomas because they also are associated with considerable
      morbidity. A better understanding of the biology of human paragangliomas, to
      encompass the molecular biology of these tumors, is essential for the development
      of a less morbid, tumor-targeted therapy. This preliminary investigation is aimed
      at testing the hypothesis that the subrenal capsule of the nude mouse is a viable
      model for in vivo study of the molecular biology of human paragangliomas. None of
      the five tumors implanted survived for the duration of the study period.
      Accordingly, the nude mouse subrenal capsule does not appear to be useful in the
      study of human paragangliomas.

PMID- 9527109
TI  - The HPV 6 E6/E7 transforming genes are expressed in inverted papilloma.
AB  - A role for human papilloma virus (HPV) infection in the pathogenesis of head and
      neck neoplasms has gained support in recent years. Expression of two early-region
      HPV genes, E6 and E7, is widely accepted as essential for viral-induced
      carcinomas of the genital tract. These oncoproteins interact with the products of
      the cellular tumor suppressor genes, p53 and retinoblastoma, and inactivate them.
      Examining E6/E7 transforming gene expression is an important step toward
      elucidating the pathogenesis of HPV in head and neck neoplasms. We introduce
      nasal inverted papilloma (IP) as a novel system for evaluating viral genomic
      expression and transforming gene regulation of tumorigenesis by virtue of its
      association to HPV infection and potential for malignant progression. We describe
      here a reverse transcriptase-polymerase chain reaction approach for the detection
      of HPV E6/E7-specific transcripts in RNA extracted from IR. A primer pair
      flanking previously mapped HPV 6 E6/E7 splice donor/acceptor sites was used to
      direct amplification of cDNA. Reverse transcriptase-polymerase chain reaction
      experiments generated products representing the 1.2 Kb E1E4 splice transcript and
      a smaller unclassified fragment in IP from two patients. These results provide
      evidence for HPV 6 E6/E7 expression in IP with the potential to encode
      transforming proteins.

PMID- 9527111
TI  - Expression of annexin II in human middle ear cholesteatoma.
AB  - Annexin II has previously been discovered to have involvements in DNA replication
      and metabolism, bone resorption, and osteoclast formation. In our work, Western
      blotting and immunohistostaining studies revealed the presence of annexin II in
      human cholesteatoma tissue. With monoclonal mouse antiannexin II antibody, a
      36,000 dalton protein (annexin II) was identified in the cholesteatoma protein
      extract. Immunoalkaline-phosphatase staining selectively localized annexin II to
      the keratinocytes in the basal and spinous layers of the cholesteatoma tissue. In
      normal human skin, annexin II is expressed mainly in the cytoplasmic membrane of
      its keratinocytes in the basal layer without significant staining in its nucleus.
      However, annexin II is expressed in both the cytoplasmic membrane and the nucleus
      of the keratinocytes in basal and spinous layers of human cholesteatomas. Our
      findings indicate a possible physiologic role of annexin II in keratinocyte cell
      hyperproliferation during development of human cholesteatoma.

PMID- 9527110
TI  - Audiologic manifestations of Noonan syndrome.
AB  - A comprehensive audiologic study of a family with Noonan syndrome is reported
      together with a review of 20 cases of this syndrome with regard to hearing
      sensitivity and middle ear status. An incidence of progressive sensorineural
      hearing loss at the high frequencies is found for 50% of the ears. It is
      emphasized that early audiologic management may improve the quality of life for
      patients with Noonan syndrome.

PMID- 9527113
TI  - Passage to India: the search for genes causing autosomal recessive nonsyndromic
      hearing loss.
AB  - Hereditary hearing impairment affects approximately 0.05% of all children born in
      the United States. It is most commonly autosomal recessive, nonsyndromic, and
      monogenic [autosomal recessive nonsyndromic hearing loss (ARNSHL)]. Although the
      number of disease loci is not known, some estimates exceed 100. Using a strategy
      of homozygosity mapping to localize ARNSHL genes by screening consanguineous
      families for chromosomal regions that are homozygous by descent, we have mapped
      several genes in multiplex, nuclear, consanguineous families in Tamil Nadu,
      India. From the mean frequency of the ARNSHL genes in this population, the total
      number of disease genes is estimated to be 57.

PMID- 9527112
TI  - Cyclandelate in the management of tinnitus: a randomized, placebo-controlled
      study.
AB  - Cyclandelate is a vasodilating agent that, like papaverine, acts directly on the
      smooth muscles of blood vessels. The drug has been used primarily as an
      adjunctive treatment for various peripheral vascular diseases; some studies
      advocate its use for treating ischemic cerebrovascular disease. Early
      nonrandomized and uncontrolled studies suggest that cyclandelate is efficacious
      in treating tinnitus. Recent personal communications regarding cyclandelate's
      effectiveness in treating tinnitus prompted this study. Fifty-nine adult patients
      with constant tinnitus for more than 1 year were randomly selected for this
      prospective, placebo-controlled, double-blind study with a treatment period of 3
      months. Audiometric testing with tinnitus pitch and loudness matching was
      performed before initiation of treatment and at the end of treatment, and
      frequent questionnaire evaluations were performed during the treatment period.
      Four patients in the cyclandelate group and three in the placebo group reported a
      subjective reduction in the loudness of their tinnitus. Audiologic testing before
      and after treatment showed no significant changes in tinnitus pitch or loudness.
      Although cyclandelate treatment was beneficial for some patients and the decrease
      in subjective loudness scoring was significant for the cyclandelate group, the
      impact of its effect did not appear to warrant its continued use by those
      patients. A significant percentage of patients could not tolerate the drug
      because of side effects.

PMID- 9527114
TI  - Interaction of methylprednisolone and transient asphyxia on the inner ear of the
      adrenalectomized rat.
AB  - Methylprednisolone has been shown clinically to have beneficial effects on
      certain types of hearing loss. In the current study, compound action potential
      (CAP) thresholds, endocochlear potentials (EPs), and potassium concentration
      (CK+) values in the endolymph were determined under conditions of transient
      asphyxia (45 seconds) and methylprednisolone treatment (24 hours) in bilateral
      adrenalectomized rats. Treatment with methylprednisolone significantly reduced
      the effect of transient asphyxia on CAP thresholds as compared with nontreated
      animals. Methylprednisolone did not alter the dramatic short-term reduction in
      the EPs produced by anoxia. Potassium concentrations in treated adrenalectomized
      rats were significantly lower before transient asphyxia than in nontreated
      adrenalectomized rats. In the nontreated rats, transient asphyxia induced a
      reduction in CK+ levels that was not seen in the methylprednisolone-treated
      animals. The data support the clinical application of methylprednisolone for
      certain forms of hearing loss and for potassium imbalance in the endolymph.

PMID- 9527115
TI  - Economic implications of chronic sinusitis.
AB  - An approach to cost analysis useful in understanding the economic implications of
      surgical intervention on chronic sinusitis is break-even time analysis. The break
      even time is the time until cost savings associated with improved health status
      after surgery equal the up-front costs of the operation itself. Data from 100
      consecutive patients undergoing sinus operation were obtained by survey before
      surgery and at quarterly intervals for 1 year with statistically validated
      outcome measures (Medical Outcome Study Short Form 36-Item Health Survey, Chronic
      Sinusitis Survey). Direct and indirect costs were obtained or derived for this
      cohort. The cost of sinus medications, including over-the-counter remedies, nasal
      steroid sprays, and antibiotics, averaged $1220 per patient per year before
      surgery and $629 after surgery (p < 0.0001), which is a 48% reduction. Surgical
      costs averaged $6490 per patient. Economic modeling predicted a break-even time
      of approximately 7 years assuming a 3% surgical revision rate per year, a 3%
      decrease in sickness-related disability, and a 5% discount rate. The model was
      sensitive to changes in the total cost of operation, the surgical revision rate,
      and the anticipated disability benefit. We conclude that significant direct and
      indirect medical cost savings may be achieved after surgical intervention for
      chronic sinusitis and these savings eventually break even with the total cost of
      surgery itself.

PMID- 9527116
TI  - Diagnosing and treating pediatric allergy.
AB  - Allergy is a significant problem in as much as 60% of patients seeking care at an
      otolaryngologist's office. This raises the issue of the most effective means of
      diagnosing allergy, especially in pediatric patients, who often may not tolerate
      skin testing. The RAST and CAP (Pharmacia) tests have been shown to be quite
      comparable with skin testing in diagnosing allergy. This study was undertaken to
      assess the effectiveness of treatment of children with allergies who had
      undergone in vitro testing. This was done by obtaining subjective symptom scores
      both before and after treatment. These were obtained from patients with different
      in vitro results, including some with negative testing. Overall, 77 of 155 mailed
      questionnaires were returned. Results showed overall improvement of 38.81 points
      in 12 symptoms (p = 0.001; n = 62). Each symptom was rated on a visual scale of 1
      to 10. A small portion of the patient population received surgical treatment
      (tympanostomy tube placement with or without adenoidectomy) in addition to
      medical treatment and avoidance. These patients did not have significantly higher
      pretreatment scores and did not have a higher improvement rate for all symptoms.
      We believe this study shows the validity of in vitro testing and treatment of
      allergy in children.

PMID- 9527117
TI  - Neurotic effects of doxycycline sclerotherapy.
AB  - A patient experienced phrenic nerve paralysis after doxycycline sclerotherapy for
      treatment of chylous fistula at our institution. The purpose of this study is to
      use physiologic testing to determine whether doxycycline is capable of inducing
      defects in neural function. A nonrandomized, controlled trial was performed with
      nerve-conduction studies to determine possible deleterious effects of doxycycline
      sclerotherapy. Thirty-eight CD rats were used and separated into four groups.
      Doxycycline was applied to the sciatic nerves of rats by either topical
      application directly on the nerve or by intraneural injection. Nerve-conduction
      studies were done before surgery and at 1,7, and 21 days after surgery. The
      results showed a statistically significant decrement in nerve-conduction velocity
      and strength of transmitted impulse in those nerves injected with doxycycline
      solution. Complete nerve block was seen frequently. This effect was not seen with
      topical application of doxycycline or normal saline solution or with intraneural
      injection of normal saline solution. This study demonstrates that doxycycline can
      induce a marked decrement in neural function when applied to the subepineural
      layers of the sciatic nerve in the rat. Therefore doxycycline sclerotherapy
      should be used with great caution in situations in which it could become exposed
      to nerves that have sustained surgical trauma.

PMID- 9527118
TI  - Clinical correlations with allelotype in supraglottic squamous cancer.
AB  - Frequent allelic loss at a genetically polymorphic locus in tumors is an
      established marker for the presence of a tumor suppressor gene in the neighboring
      chromosomal region. This technique can be used to identify novel tumor suppressor
      genes and to monitor their status before the cloning of the gene itself. We have
      used the polymerase chain reaction and microsatellite loci on all 39
      nonacrocentric autosomal chromosomal arms to identify sites of frequent allelic
      loss in squamous cell carcinomas of the supraglottic larynx. Our allelotype
      identified seven chromosomal arms (3p, 5q, 8p, 9p, 9q, 13q, and 17p) likely to
      contain tumor suppressor genes frequently inactivated during squamous
      tumorigenesis in the larynx. We tested for associations between allelic losses on
      these chromosomal arms and the clinical and histopathologic features of these
      tumors. There were no correlations with either T or N classifications. Allelic
      loss on chromosomal arm 13q is significantly associated with a number of
      histopathologic features characteristic of poorly differentiated or
      histologically aggressive tumors. Allelic loss on this arm also exhibits
      statistical trends toward association with early tumor recurrence and poor
      survival. The association with survival was substantiated by a multivariate Cox
      proportional hazards model.

PMID- 9527119
TI  - XeCl laser surgery of the vocal cords: a histologic comparison with CO2 laser in
      a porcine model.
AB  - Fresh cadaveric pig larynxes were ablated with a CO2 (lambda = 10.6 microm) and a
      XeCl excimer (lambda = 308 nm) laser. Histologic comparison of the ablation
      craters created by the two lasers was performed, and ablation crater depth and
      marginal tissue damage were measured. Crater depth for both laser treatments is
      correlated with energy deposition and exposure time. The CO2 laser creates three
      times more nonspecific, marginal tissue damage than the XeCl laser at the ranges
      of total energy and exposure times used. This study demonstrates the potential of
      the XeCl laser as an alternative to the CO2 laser in microlaryngeal surgery.

PMID- 9527120
TI  - Tracheostomy for long-term laryngeal experimentation.
AB  - To perform laryngeal research involving long-term survival surgery, a permanent
      tracheostomy is often necessary. For experiments using a long-term induced canine
      phonation model, we required a tracheostomy that was placed as low as possible,
      to maximize the subglottic space superior to the stoma. The ideal experimental
      tracheostomy would also be safe and easy to perform, require no tracheostomy
      tube, and be low maintenance, requiring minimal cleaning or suctioning.
      Tracheostomies were performed in 37 dogs based on previously published methods.
      If the stoma was placed below the twelfth tracheal ring, the perioperative
      mortality rate was 57% because of kinking of the trachea and subsequent airway
      obstruction. When the tracheostomy was performed above this level, the mortality
      rate was reduced to 3%. A number of significant modifications in technique were
      made to achieve this improvement and resulted in the last 12 dogs having no
      complications. Several of the tracheostomies were maintained for more than 18
      months. The method derived meets the above criteria for the ideal experimental
      tracheostomy and also meets our needs for a long-term induced phonation model.

PMID- 9527121
TI  - Vocal cord polypectomy with fiberoptic sinus endoscopes.

PMID- 9527122
TI  - Laryngeal lymphangioma: a case report of an uncommon entity.

PMID- 9527123
TI  - Osteosarcoma of the larynx.

PMID- 9527124
TI  - Larynx preservation: the discussion is not closed.
AB  - Advanced but resectable larynx and hypopharynx squamous cell carcinomas are, in
      the vast majority of cases, treated by radical surgery and postoperative
      irradiation, resulting in the total ablation of the voice box. Some institutions
      prefer to use irradiation and reserve radical surgery for salvage. There is no
      randomized comparison of results obtained with these two strategies. Induction
      chemotherapy with the use of platinum and 5-fluorouracil provides notable
      response rates and allows the prediction of radiosensitivity in those patients
      who show a response to chemotherapy. This has been the basis of the most frequent
      larynx preservation approach: induction chemotherapy followed by irradiation in
      good responders or by radical surgery in poor responders. This strategy did not
      jeopardize survival and allowed larynx preservation in 50% to 66% of survivors.
      These results are of importance but it should nonetheless be remembered that
      irradiation is an efficient treatment of these tumors and may have an improved
      activity (with modified fractionation or concurrent administration of
      chemotherapy and irradiation) and that selected cases are amenable to subtotal
      laryngectomy. On the other hand, new prospects for treatment are emerging
      (biologic tools, place of imaging), as well as new parameters for the success of
      treatment (quality of life, quality of preserved function, cost effectiveness).
      In summary, larynx preservation is undoubtedly feasible but remains
      investigational.

PMID- 9527125
TI  - Sudden deafness: lack of evidence for systemic viral infection.
AB  - The cause of sudden deafness remains unknown even though available evidence
      suggests that viral infection could be one factor involved. The presence of an
      interferon-inducible protein termed MxA in patients' leukocytes is a good marker
      of a systemic viral infection. This study included 20 patients with sudden
      deafness and 12 control subjects. Peripheral blood leukocytes obtained from the
      patients with sudden deafness did not express significantly higher levels of
      interferon-alpha/beta-inducible MxA protein than control subjects. In addition,
      no measurable interferon-alpha activity was detected in any of the serum
      specimens. These findings suggest that sudden deafness is not commonly associated
      with a systemic viral infection.

PMID- 9527126
TI  - Predictive value of an adherence test for acute otitis media.
AB  - The predictive value of an in vitro adherence test of the bacterium Streptococcus
      pneumoniae for the development of recurrent otitis media was calculated 5 years
      after the initial test. Nasopharyngeal cells from 56 children suffering from
      acute otitis media (AOM) and from healthy children were tested for adherence of a
      standard pneumococcal type (capsular serotype 6). The average adherence of the
      bacteria to epithelial cells from the group suffering from AOM was greater than
      the average adherence in the control group (p < 0.005), both when adherence was
      counted microscopically and radioactively. Subjects were followed up periodically
      over a 5-year period. Four out of 5 healthy children who had high mean adherence
      values experienced AOM during the 5 years, and 1 child classified as AOM-prone
      was found to be healthy. Based on the retrospective data, the positive predictive
      value of this test was 98.2%, and the negative predictive value was 90.7%.

PMID- 9527127
TI  - Intraductal papillary adenocarcinoma of the submandibular gland.

PMID- 9527128
TI  - Nasal septal tumor as a sole presentation in the head and neck region in Rosai
      Dorfman disease.

PMID- 9527129
TI  - Inappropriate secretion of antidiuretic hormone caused by the local regional
      recurrence of hypopharyngeal cancer.

PMID- 9527130
TI  - Chondromyxoid fibroma of the skull base.

PMID- 9527131
TI  - Oncocytic metaplasia of the nasopharynx.

PMID- 9527132
TI  - Dermatophytid reaction and chronic otitis externa.

PMID- 9527133
TI  - Fluoxetine for treatment of tinnitus.

PMID- 9527134
TI  - Cochlear implantation in prelingually deaf children.

PMID- 9527135
TI  - The role of the axolemma in the initiation of traumatically induced axonal
      injury.

PMID- 9527136
TI  - CSF tests for dementia: a potential headache?

PMID- 9527137
TI  - Neurology and the heart.

PMID- 9527138
TI  - Cerebrospinal fluid tau protein as a biochemical marker for Alzheimer's disease:
      a community based follow up study.
AB  - OBJECTIVES: Biochemical markers for Alzheimer's disease would be of great value,
      especially to help in diagnosis early in the course of the disease. A pronounced
      increase in CSF tau protein (CSF-tau) is found in most patients with Alzheimer's
      disease. However, the specificity has to be further studied, as an increase in
      CSF-tau has also been found in other dementias, especially in vascular dementia.
      As most previous CSF studies have been based on selected inpatients, it was
      considered of special interest to examine the diagnostic potential of CSF-tau in
      a community population based sample of consecutive patients with dementia. Such
      patient material has been examined at the Pitea River Valley Hospital in Northern
      Sweden since 1986, and includes all those with memory disturbances in the
      community. The aim was also to study if an increase in CSF-tau is found early in
      the disease process, and whether CSF-tau changes during the progression of
      disease. METHODS:  PARTICIPANTS: Community population based sample of 75 demented
      patients (43 with Alzheimer's disease, 21 with vascular dementia, and 11 with
      mixed Alzheimer's disease/vascular dementia), 18 healthy subjects, and 18
      neurological controls. A follow up investigation (including analysis of a new CSF
      sample) was performed in all patients after about one year. MAIN OUTCOME
      MEASURES: Concentrations of total (both normal tau and PHF-tau) tau in CSF,
      clinical measures (duration and severity of dementia), and apoE polymorphism.
      RESULTS: CSF-tau was markedly increased in Alzheimer's disease, 41/43 (95%)
      patients had values above the cut off level (mean+2 SD) in controls (306 pg/ml).
      High CSF-tau concentrations were also found in most patients with vascular
      dementia, preferentially in patients with vascular dementia without progressive
      leukoaraiosis on CT, whereas patients with vascular dementia with progressive
      leukoaraiosis had normal CSF-tau. Concentrations of CSF-tau were stable at one
      year follow up in both patients with Alzheimer's disease and patients with
      vascular dementia, and there was no correlation between CSF-tau and either
      duration or severity of dementia. CONCLUSIONS: The findings confirm the high
      sensitivity of CSF-tau for the diagnosis of Alzheimer's disease, but high CSF-tau
      was also found in vascular dementia, resulting in a lower specificity. However,
      high CSF-tau is preferentially found in patients with vascular dementia without
      progressive leukoaraiosis, which may constitute a group with concomitant
      Alzheimer's disease pathology. High CSF-tau may be present during the whole
      course of the disease in Alzheimer's disease. Possibly, therefore, the same high
      CSF-tau concentrations may be present before the onset of clinical dementia.
      Follow up studies on such patients will tell whether analysis of CSF-tau is
      useful as a biochemical marker for early Alzheimer's disease.

PMID- 9527139
TI  - A clinical role for 99mTc-HMPAO SPECT in the investigation of dementia?
AB  - OBJECTIVES: To provide the clinician with a guide to the clinical utility of
      99mTc-HMPAO single photon emission computed tomography (SPECT) and to the
      interpretation of specific test results in the differential diagnosis of
      dementia. METHODS: Three hundred and sixty three patients with dementia were
      studied prospectively for a median three (range 1-6) years and classified into
      disease groups on the basis of established clinical criteria. The degree to which
      different patterns of cerebral blood flow (CBF) abnormality found on 99mTc-HMPAO
      SPECT imaging at the time of initial patient presentation modified clinical
      diagnoses was determined by calculating the likelihood ratios for pairwise
      disease group comparisons. The optimal clinical usage of 99mTc-HMPAO SPECT was
      determined by calculating the percentage of significant test results for each
      pairwise disease group comparison. RESULTS: Bilateral posterior CBF abnormality
      was found to significantly increase the odds of a patient having Alzheimer's
      disease as opposed to vascular dementia or frontotemporal dementia. Bilateral
      anterior CBF abnormality significantly increased the odds of a patient having
      frontotemporal dementia as opposed to Alzheimer's disease, vascular dementia, or
      Lewy body disease. "Patchy" CBF changes significantly increased the odds of a
      patient having vascular dementia as opposed to Alzheimer's disease. Unilateral
      anterior, unilateral anterior plus unilateral posterior, and generalised CBF
      abnormality failed to contribute to the differentiation of any of these forms of
      dementia. CONCLUSIONS: 99mTc-HMPAO SPECT was found to be most useful in
      distinguishing Alzheimer's disease from vascular dementia and fronto temporal
      dementia, and least useful in differentiating between Alzheimer's disease and
      Lewy body disease, and between vascular dementia, frontotemporal dementia, and
      progressive aphasia. It is suggested that CBF SPECT should be used selectively
      and as an adjunct to clinical evaluation and CT.

PMID- 9527140
TI  - Measuring the rate of progression and estimating the preclinical period of
      Parkinson's disease with [18F]dopa PET.
AB  - OBJECTIVES: To measure the rate of progression in striatal [18F]dopa metabolism
      in a large group (n=32) of patients with Parkinson's disease, to estimate the
      average duration of preclinical period, and to examine the influence of the PET
      method on the assessment of rate of progression and preclinical period. METHODS:
      Thirty two patients with Parkinson's disease (mean age 58 (SD 13) years, mean
      duration 39 (SD 33) months) were assessed with [18F]dopa PET and UPDRS scoring on
      two occasions a mean of 18 (SD 6) months apart. PET data were sampled with
      separate caudate and putamen and total striatal regions of interest, and both
      graphical (Ki) and ratio methods of analysis. RESULTS: The mean annual rate of
      deterioration in [18F]dopa uptake varied according to structure and method of
      analysis, with putamen Ki showing the most rapid mean rate of progression (4.7%
      of normal mean per year). The group showed a significant deterioration (p<0.0004,
      paired two tailed t test) in UPDRS and in the putamen (p=0.008) and total
      striatal (p=0.012) [18F]dopa uptake measured using a graphical analysis, but no
      significant change in caudate or putamen uptake measured by a ratio approach. A
      study of sensitivity confirmed that putamen Ki was the most sensitive measure of
      disease progression, caudate ratio the least. Symptom onset in Parkinson's
      disease was estimated at a mean putamen [18F]dopa uptake (Ki) of 75% of normal
      and a mean caudate [18F]dopa uptake (Ki) of 91% of normal. CONCLUSIONS:
      Estimation of mean rate of progression varies according to the sensitivity of a
      functional imaging method to clinical severity. Sensitivity and reproducibility
      of method must be considered when designing studies of disease progression and
      neuroprotection. The mean preclinical period in Parkinson's disease is unlikely
      to be longer than seven years.

PMID- 9527142
TI  - Decreased driving ability in people with Parkinson's disease.
AB  - BACKGROUND: Driving is a complex form of activity involving especially cognitive
      and psychomotor functions. These functions may be impaired by Parkinson's
      disease. The relation between Parkinson's disease and driving ability is still
      obscure and clinicians have to make decisions concerning the driving ability of
      their patients based on insufficient information. Until now no studies have
      compared different methods for evaluating the driving ability of patients with
      Parkinson's disease. METHODS: The driving ability of 20 patients with idiopathic
      Parkinson's disease and 20 age and sex matched healthy control subjects was
      evaluated by a neurologist, psychologist, vocational rehabilitation counsellor,
      and driving instructor using a standard 10 point scale. The patients and controls
      also evaluated their own driving ability. Cognitive and psychomotor laboratory
      tests and a structured on road driving test were used for evaluating the
      subjects' driving ability. RESULTS: The patients with Parkinson's disease
      performed worse than the controls both in the laboratory tests and in the driving
      test. There was a high correlation between the laboratory tests and driving test
      both in the patient group and in the control group. Disease indices were not
      associated with the driving test. The neurologist overestimated the ability of
      patients with Parkinson's disease to drive compared with the driving ability
      evaluated by the structured on road driving test and with the driving related
      laboratory tests. Patients themselves were not capable of evaluating their own
      ability reliably. CONCLUSION: Driving ability is greatly decreased in patients
      with even mild to moderate Parkinson's disease. The evaluation of patients'
      driving ability is very difficult to carry out without psychological and
      psychomotor tests and/or a driving test.

PMID- 9527143
TI  - Louis Pasteur (1822-95).

PMID- 9527141
TI  - Spontaneous and reflex activity of facial muscles in dystonia, Parkinson's
      disease, and in normal subjects.
AB  - OBJECTIVE: The blink rate is an index which can be easily obtained during the
      clinical examination, but it has not yet been properly standardised. The present
      study was undertaken to collect data on the age dependent development of this
      index and on possible abnormalities in Parkinson's disease and dystonia. METHODS:
      The blink rate and the rate of perioral movements were measured in 156 normal
      controls, 51 patients with Parkinson's disease, 48 patients with spasmodic
      torticollis, 14 patients with generalised dystonia, and 12 patients with focal
      hand or leg dystonias and have been correlated with the results of testing the
      orbicularis oculi reflex, the palmomental reflex, and the perioral reflex.
      RESULTS: No age related effects were found for the blink rate and perioral
      movements but all the reflexes showed age dependent variations. It is sufficient
      to measure the blink rate for one minute, provided standardised conditions are
      applied. Blink rate and perioral movement rate were positively correlated in
      patients and controls. The blink rate was significantly increased in spasmodic
      torticollis and decreased in Parkinson's disease. In generalised dystonia the
      blink rate was increased but in hand and leg dystonia the blink rate was normal.
      The reflex tests did not significantly differ between the subject groups except
      for the orbicularis oculi reflex, which was hyperexcitable in Parkinson's
      disease. CONCLUSION: Measuring the blink rate can assist the diagnosis of
      extrapyramidal disorders as a soft sign, but is not very sensitive. The group
      differences found indicate a decrease of the blink rate and perioral movements in
      hypokinetic and an increase in hyperkinetic extrapyramidal disorders such as
      spasmodic torticollis and generalised dystonias. This may be of interest for
      future pathophysiological studies.

PMID- 9527145
TI  - Cognitive complaints in patients after whiplash injury: the impact of
      malingering.
AB  - OBJECTIVES: The validity of memory and concentration complaints that are often
      reported after a whiplash trauma is controversial. The prevalence of malingering
      or underperformance in post-whiplash patients, and its impact on their cognitive
      test results were studied. METHODS: The Amsterdam short term memory (ASTM) test,
      a recently developed malingering test, was used as well as a series of
      conventional memory and concentration tests. The study sample was a highly
      selected group of patients, who were examined either as part of a litigation
      procedure (n=36) or in the normal routine of an outpatient clinic (n=72).
      RESULTS: The prevalence of underperformance, as defined by a positive score on
      the malingering test, was 61% (95% CI: 45-77) in the context of litigation, and
      29% (95% CI: 18-40) in the outpatient clinic (p=0.003). Furthermore, the scores
      on the memory and concentration test of malingering post-whiplash patients (n=43)
      and non-malingering post-whiplash patients (n=65) were compared with the scores
      of patients with closed head injury (n=20) and normal controls (n=46). The
      malingering post-whiplash patients scored as low as the patients with closed head
      injury on most tests. CONCLUSIONS: The prevalence of malingering or cognitive
      underperformance in late post-whiplash patients is substantial, particularly in
      litigation contexts. It is not warranted to explain the mild cognitive disorders
      of whiplash patients in terms of brain damage, as some authors have done. The
      cognitive complaints of non-malingering post-whiplash patients are more likely a
      result of chronic pain, chronic fatigue, or depression.

PMID- 9527144
TI  - Dissociation of sensory-attentional from motor-intentional neglect.
AB  - OBJECTIVES: Spatial neglect may result from disruption of sensory-attentional
      systems that spatially allocate perceptual resources and the motor-intentional
      systems that direct exploration and action. Previous studies have suggested that
      the line bisection task is more sensitive to sensory-attentional disorders and
      the cancellation task to motor-intentional disorders. A new technique was
      developed that allows the dissociation of sensory-attentional and motor
      intentional deficits in both tasks and thereby allows comparison of these tasks.
      METHODS: Ten patients with right hemispheric injury and hemispatial neglect
      performed line bisection and cancellation tasks while viewing stimuli on closed
      circuit TV. Direct view of the exploring hand and the target was precluded; the
      TV monitor guided performance. The direct condition made the direction of hand
      movement on the table (workspace) congruent with that on the monitor. Inverting
      the camera produced the indirect condition wherein the lateral movement in the
      workspace occurred in the opposite direction on the monitor. RESULTS: On the
      cancellation task, five patients marked targets in the right workspace in the
      direct condition but the left workspace in the indirect condition, indicating
      sensory-attentional neglect. However, four other patients cancelled targets only
      in the right workspace in both conditions, failing to explore the left workspace,
      suggesting motor-intentional neglect. A patient who performed ambiguously may
      have elements of both types of neglect. Only two out of five patients designated
      as sensory-attentional in cancellation tasks showed sensory neglect on line
      bisection. The other three patients, as well as patients defined as motor
      intentional by cancellation performance, exhibited motor-intentional neglect on
      line bisection. CONCLUSION: The designation of sensory-attentional versus motor
      intentional neglect therefore, in part, depends on task specific demands.

PMID- 9527147
TI  - Circumstances of death in sudden death in epilepsy: interviews of bereaved
      relatives.
AB  - OBJECTIVES: To study the circumstances of death in sudden death in epilepsy.
      METHODS: Self referred bereaved relatives of patients with epilepsy who had died
      suddenly were interviewed with information obtained substantiated through other
      sources-namely, coroners' officers' reports, postmortem reports, previous medical
      records, and EEG reports. RESULTS: Of 34 cases, 26 were classified as sudden
      unexpected deaths in epilepsy (SUDEP). Twenty four of 26 cases of SUDEP were
      unwitnessed. Evidence indicative or suggestive of a seizure was found in most. In
      11 of 26 the position of the head was such that breathing could have been
      compromised. Cases included both localisation related and idiopathic primary
      generalised epilepsy. Only three were in remission at the time of death. Most
      relatives expressed the view that they would have preferred to have known that
      epilepsy could be fatal. CONCLUSIONS: Although the deaths in question were
      largely unwitnessed, the available evidence suggested that most cases of SUDEP
      represented ictal or postictal seizure deaths, occurring in people with a history
      of generalised tonic clonic seizures, and in both primary generalised and
      localisation related epilepsy. These interviews highlight the needs of bereaved
      relatives and their sense of isolation in the face of an entirely unexpected and
      apparently unexplained loss.

PMID- 9527146
TI  - Piracetam relieves symptoms in progressive myoclonus epilepsy: a multicentre,
      randomised, double blind, crossover study comparing the efficacy and safety of
      three dosages of oral piracetam with placebo.
AB  - OBJECTIVE: To compare the efficacy, tolerability, and safety of three daily
      dosage regimens of oral piracetam in patients with progressive myoclonus
      epilepsy. METHODS: Twenty patients (12 men, eight women), aged 17-43 years, with
      classical Unverricht-Lundborg disease were enrolled in a multicentre, randomised,
      double blind trial of crossover design in which the effects of daily doses of 9.6
      g, 16.8 g, and 24 g piracetam, given in two divided doses, were compared with
      placebo. The crossover design was such that patients received placebo and two of
      the three dosage regimens of piracetam, each for two weeks, for a total treatment
      period of six weeks and thus without wash out between each treatment phase. The
      primary outcome measure was a sum score representing the adjusted total of the
      ratings of six components of a myoclonus rating scale in which stimulus
      sensitivity, motor impairment, functional disability, handwriting, and global
      assessments by investigators and patients were scored. Sequential clinical
      assessments were made by the same neurologist in the same environment at the same
      time of day. RESULTS: Treatment with 24 g/day piracetam produced significant and
      clinically relevant improvement in the primary outcome measure of mean sum score
      (p=0.005) and in the means of its subtests of motor impairment (p=0.02),
      functional disability (p=0.003), and in global assessments by both investigator
      (p=0.002) and patient (p=0.01). Significant improvement in functional disability
      was also found with daily doses of 9.6 g and 16.8 g. The dose-effect relation was
      linear and significant. More patients showed clinically relevant improvement with
      the highest dosage and, in individual patients, increasing the dose improved
      response. Piracetam was well tolerated and adverse effects were few, mild, and
      transient. CONCLUSIONS: This study provides further evidence that piracetam is an
      effective and safe medication in patients with Unverricht-Lundborg disease. In
      addition, it shows that a dose of 24 g is highly beneficial, more effective than
      lower doses and that a dose-effect relation exists. There is considerable
      variation in optimal individual dosage.

PMID- 9527149
TI  - Respiratory insufficiency due to high anterior cervical cord infarction.
AB  - OBJECTS AND METHODS: Respiratory dysfunction may occur as a result of lesions in
      the upper cervical spinal cord disturbing the descending pathways subserving
      automatic and volitional ventilatory control. Four patients are described who
      presented with acute respiratory insufficiency caused by infarction of the
      anterior portion of the upper cervical cord due to presumed anterior spinal
      artery occlusion. RESULTS: Two patients presented after respiratory arrests; they
      were ventilated and there was no automatic or volitional respiratory effort. Both
      had signs of an extensive anterior spinal cord lesion at the C2 level and this
      was confirmed by MRI. One patient presented with a C4 infarction and required
      ventilation for three months. Ventilatory recovery was characterised by the
      development of an automatic respiratory pattern. The fourth patient required
      ventilation for two months after infarction at the C3 level. On attempted weaning
      he had prolonged periods of hypoventilation and apnoea during inattention and
      sleep indicating impairment of automatic respiratory control. CONCLUSION:
      Infarction of the spinal cord at high cervical levels may be due to
      fibrocartilaginous embolism and involvement of the descending respiratory
      pathways may occur. Extensive lesions at C1/2 cause complete interruption of
      descending respiratory control leading to apnoea. Partial lesions at C3/4 cause
      selective interruption of automatic or voluntary pathways and give rise to
      characteristic respiratory patterns. The prognosis depends on the level and
      extent of the lesion.

PMID- 9527148
TI  - Asymptomatic spinal cord lesions in clinically isolated optic nerve, brain stem,
      and spinal cord syndromes suggestive of demyelination.
AB  - OBJECTIVES: Conventional T2 weighted MRI studies have highlighted the fact that
      the presence of clinically silent brain lesions increases the risk of developing
      clinically definite multiple sclerosis after an isolated syndrome of the optic
      nerve, brain stem, or spinal cord. The objectives of the present study are: (1)
      to show whether or not these patients also have asymptomatic abnormalities of the
      spinal cord, and (2) to recruit a new cohort of such patients using high
      resolution MRI of both brain and spinal cord. METHODS: The brain was imaged in
      the axial plane with 3 mm thick contiguous slices using a proton density and T2
      weighted fast spin echo (FSE) sequence; a T1 weighted sequence after the
      injection of gadolinium-DTPA; and a fast fluid attenuated inversion recovery
      (fFLAIR) sequence. The spinal cord was imaged in the sagittal plane with 3 mm
      thick slices using a T2 weighted FSE and a T1 weighted gadolinium enhanced
      sequence. RESULTS: Thirty three patients, mean age 31 (16-46) were recruited.
      There were 14 men and 19 women. Brain MRI was abnormal in 22 (67%); no patient
      was seen with abnormalities on only one or other sequence. Six patients (18%)
      displayed one or more gadolinium enhancing lesions on brain MRI. In the spinal
      cord, nine (27%) patients displayed one or more clinically silent lesions on FSE.
      Two patients showed one and two gadolinium enhancing lesions in the spinal cord
      respectively. CONCLUSION: This high incidence of spinal cord lesions emphasises
      that asymptomatic demyelinating lesions may also involve clinically eloquent
      pathways. Follow up studies are required to determine their prognostic
      importance.

PMID- 9527150
TI  - Muscle fibre characteristics and lactate responses to exercise in chronic fatigue
      syndrome.
AB  - OBJECTIVES: To examine the proportions of type 1 and type 2 muscle fibres and the
      degree of muscle fibre atrophy and hypertrophy in patients with chronic fatigue
      syndrome in relation to lactate responses to exercise, and to determine to what
      extent any abnormalities found might be due to inactivity. METHODS: Quadriceps
      needle muscle biopsies were obtained from 105 patients with chronic fatigue
      syndrome and the proportions of type 1 and 2 fibres and fibre atrophy and
      hypertrophy factors were determined from histochemical preparations, using a
      semiautomated image analysis system. Forty one randomly selected biopsies were
      also examined by electron microscopy. Lactate responses to exercise were measured
      in the subanaerobic threshold exercise test (SATET). RESULTS: Inactivity would be
      expected to result in a shift to type 2 fibre predominance and fibre atrophy, but
      type 1 predominance (23%) was more common than type 2 predominance (3%), and
      fibre atrophy was found in only 10.4% of cases. Patients with increased lactate
      responses to exercise did have significantly fewer type 1 muscle fibres (p<0.043
      males, p<0.0003 females), but there was no evidence that this group was less
      active than the patients with normal lactate responses. No significant
      ultrastructural abnormalities were found. CONCLUSION: Muscle histometry in
      patients with chronic fatigue syndrome generally did not show the changes
      expected as a result of inactivity. However, patients with abnormal lactate
      responses to exercise had a significantly lower proportion of mitochondria rich
      type 1 muscle fibres.

PMID- 9527151
TI  - Ataxia with isolated vitamin E deficiency presenting as mutation negative
      Friedreich's ataxia.
AB  - Ataxia with vitamin E deficiency is an autosomal recessive condition associated
      with a defect in the a-tocopherol transfer protein. Clinically it manifests as a
      progressive ataxia with a phenotype resembling that of Friedreich's ataxia. There
      is some evidence that progression of neurological symptoms is prevented by
      vitamin E therapy. A patient is described who was given a clinical diagnosis of
      Friedreich's ataxia. Molecular genetic analysis showed the absence of the
      frataxin gene expansion. Subsequent vitamin E assay showed deficiency and a
      diagnosis of ataxia with vitamin E deficiency was made. It is recommended that
      all patients with ataxia of unknown cause should have vitamin E deficiency
      excluded. When a diagnosis of Friedreich's ataxia is considered patients should
      have frataxin analysis in addition. Further, neurologists should be aware that
      ataxia with vitamin E deficiency may present as "mutation negative" Friedreich's
      ataxia.

PMID- 9527152
TI  - Depression and its relation to lesion location after stroke.
AB  - The study of discrete organic cerebral lesions resulting in clearly definable
      psychiatric disorders may provide an understanding of the underlying
      pathophysiological basis of these disorders. However, the relation between lesion
      location and psychiatric illness after stroke remains unclear. Fifty five
      patients referred to hospital were identified who had a single lesion on CT which
      was consistent with their neurological presentation and who did not have evidence
      of a persistent affective disorder at the time of the stroke. Six months after
      stroke standardised psychiatric assessment disclosed that 26% of the patients met
      DSM-IV criteria for an anxiety or depressive disorder, with depression the most
      common diagnosis (20%). Pathological emotionalism was diagnosed in 18% of
      patients, particularly those who were depressed (p<0.0001). Depression was
      significantly associated with larger lesions involving the right cerebral
      hemisphere (p=0.01). The importance of depression as a consequence of stroke has
      been clarified by the studies in this area. However, wide confidence intervals
      support the possibility that significant results may be due to chance. A
      systematic review of these studies is now needed if a consensus is to be reached.

PMID- 9527153
TI  - Disturbances of affective prosody in patients with schizophrenia; a cross
      sectional study.
AB  - The objective was to determine whether disturbances of affective prosody
      constitute part of the symptomatology of schizophrenia. Affective prosody is
      defined here as a neuropsychological function that encompasses all non-verbal
      aspects of language that are necessary for recognising and conveying emotions in
      communication. Twenty six schizophrenic outpatients and twenty four normal
      controls underwent a standardised prosody test, assessing four different aspects
      of affective prosody: spontaneous prosody, prosodic recognition, prosodic
      repetition, and facial affect recognition. Patients scored significantly worse
      than controls on three of the four subtests: spontaneous prosody, prosodic
      recognition, and prosodic repetition. There were no significant differences on a
      subtest for facial affect recognition. Differences in educational level between
      patients and controls could not account for these differences.

PMID- 9527154
TI  - Treatment of accidental high dose intraventricular mezlocillin application by
      cerebrospinal fluid exchange.
AB  - An accidental high dose of intraventricular mezlocillin was given during
      antibiotic treatment for pneumonia in a patient admitted because of severe
      traumatic brain injury and occlusive hydrocephalus. Because of serial epileptic
      seizures not responsive to antiepileptic drug treatment, CSF exchange was
      performed. The CSF was drained through a ventricular catheter, while mock CSF was
      infused into the lumbar subarachnoid space. The patient soon recovered to her
      clinical status previous to intraventricular mezlocillin application. Side
      effects of CSF exchange were not seen. Under continued antiepileptic medication
      no more seizures occurred. It is concluded that high doses of intraventricular
      mezlocillin have proconvulsive effects. In this patient CSF exchange was a
      suitable means of preventing putatively permanent impairment of brain function
      caused by serial epileptic seizures due to intraventricular mezlocillin
      application.

PMID- 9527155
TI  - Behcet's syndrome: a report of 41 patients with emphasis on neurological
      manifestations.
AB  - Forty one patients with the clinical diagnosis of Behcet's syndrome from two
      teaching hospitals in Kuwait were studied. There were 34 male and seven female
      patients. Age at presentation ranged from 14 to 48 years. Neurological
      manifestations were present in 24 patients. Eleven patients showed evidence of
      increased intracranial pressure, and 10 of these had radiologically confirmed
      dural sinus thrombosis. Five patients presented with a meningoencephalitic or
      meningomyelitic picture, three with a stroke-like picture, and three with
      primarily brain stem signs. One patient developed trigeminal neuritis, and five
      patients exhibited (along with other features) variable degrees of psychological
      manifestations. All patients with neurological involvement were treated with
      steroids, and some also had courses of other immunosuppressant drugs and
      colchicine. The disease took a relatively benign course, except those patients
      with meningoencephalitic and meningomyelitic presentation, one of whom died from
      the disease. Those treated early had a better prognosis. The incidence of dural
      sinus thrombosis in this series of patients is unusually high. In most patients,
      the course of the disease was more favourable than reported in the literature.
      This may be attributed to early and aggressive treatment.

PMID- 9527156
TI  - Cough responsiveness in neurogenic dysphagia.
AB  - OBJECTIVES: In neurogenic dysphagia a good cough is important for airway
      protection. If triggering of cough, or its effectiveness, is impaired this might
      result in an increased aspiration risk. Capsaicin, an agent which induces cough
      through sensory nerve stimulation, was used to test cough sensitivity in groups
      of patients with and without neurogenic dysphagia. METHODS: On the basis of
      swallowing speed (ml/s) in a validated water test 28 alert neurological
      inpatients (16 women, aged 22-71 years) were classified into 13 with abnormal and
      15 with normal swallowing (median swallowing speed 23% and 99%, median
      volume/swallow 43% and 106% of that predicted for age and sex respectively:
      p<0.001). Capsaicin nebulised on air in saline was inhaled via a low resistance
      valve using a mouthpiece and noseclip. Up to seven incremental concentrations of
      capsaicin ranging from 0.07-20.0 x 10(-4) mol/l were each inhaled for up to a
      minute. A pneumotachograph connected to the expiratory limb gave a paper
      recording of expiratory air flow. Coughs were recorded as high flow expirations
      of short duration. Capsaicin concentrations at first cough (threshold) were
      recorded; concentrations at frequencies of 10 and 20 coughs/minute were
      interpolated from the dose-response curve. RESULTS: Cough threshold tended to be
      lower in those with abnormal swallowing (non-significant): the (log)
      concentration of capsaicin producing 10 or 20 coughs/ minute also tended to be
      lower (p=0.12 and 0.07 respectively) in those with abnormal swallowing.
      CONCLUSION: Contrary to expectation, these results suggest that cough
      responsiveness is enhanced in alert patients with neurogenic dysphagia even after
      allowing for diagnostic category, the possible presence of a bulbar upper motor
      neuron lesion, or voluntary respiratory capacity. It is concluded that these
      patients with neurogenic dysphagia do not have a reduced sensitivity of cough
      triggering.

PMID- 9527157
TI  - Stress induced urinary incontinence in patients with spinocerebellar
      degeneration.
AB  - OBJECTIVES: To examine the pathophysiology of "stress induced urinary
      incontinence" (urinary incontinence evoked by abdominal straining) in patients
      with spinocerebellar degeneration. METHODS: Micturitional symptoms of 184
      patients with spinocerebellar degeneration who were admitted to hospital were
      studied repeatedly. Urodynamic studies were made in symptomatic patients, and
      consisted of uroflowmetry, measurement of residual urine, urethral pressure
      profilometry, medium fill water cystometry, and external sphincter EMG. RESULTS:
      Twenty nine (15.8%) patients with spinocerebellar degeneration showed stress
      induced urinary incontinence. Twenty of the 29 patients had detrusor
      overactivity, low compliance detrusor, or residual urine, resembling urgency and
      overflow types of incontinence (complicated form). The other nine had none of
      these findings (pure form), but showed decreased maximum urethral closure
      pressure in four, absence of bulbocavernosus reflex in two, absence of voluntary
      sphincter contraction in one, incompetent urinary storage even at the first
      sensation in two, and high amplitude and polyphasic neurogenic changes in three
      of five patients studied, indicative of neurogenic sphincter dysfunction.
      CONCLUSIONS: Stress induced urinary incontinence in spinocerebellar degeneration
      had various underlying mechanisms. Some of the patients only showed evidence of
      pudendal denervation, which can cause external sphincter weakness and may reflect
      lesions of the sacral Onuf's nucleus and the pudendal nerve. Urodynamic studies
      are necessary to evaluate stress induced urinary incontinence in patients with
      spinocerebellar degeneration, to prescribe appropriate therapies.

PMID- 9527158
TI  - Midbrain infarction: associations and aetiologies in the New England Medical
      Center Posterior Circulation Registry.
AB  - Most reports of midbrain infarction have described clinicoanatomical correlations
      rather than associations and aetiologies. Thirty nine patients with midbrain
      infarction (9.4%) are described out of a series of 415 patients with
      vertebrobasilar ischaemic lesions in the New England Medical Center Posterior
      Circulation Registry. Patients were categorised according to the rostral-caudal
      extent of infarction. The "proximal" vertebrobasilar territory includes the
      medulla and posterior inferior cerebellar artery territory. The "middle"
      territory includes the pons and anterior inferior cerebellar artery territory.
      The "distal" territory includes the rostral midbrain, thalami, superior
      cerebellum, and medial temporal and occipital lobes. Midbrain infarction was
      accompanied by "proximal" territory infarcts in four patients, and by "middle"
      territory infarction in 19 patients. Thirteen patients had associated "distal"
      territory infarcts, three of whom had occipital or temporal lobe infarcts. Only
      three patients had isolated midbrain infarcts. Cardioembolism (n=11), in situ
      thrombosis (n=9), large artery to artery embolism (n=7), and intrinsic branch
      penetrator disease (n=5) were the most common aetiologies. Bilateral infarction
      and accompanying pontine infarction were associated with the most extensive
      vertebrobasilar occlusive disease. Midbrain infarction was 10-fold more likely to
      be accompanied by ischaemia of neighbouring structures than it was to occur in
      isolation. Recognition of the different patterns of infarction may act as a guide
      to the underlying aetiology and vascular lesions.

PMID- 9527159
TI  - Absence of characteristic features in two patients with inclusion body myositis.
AB  - According to recently published criteria a diagnosis of definite sporadic
      inclusion body myositis is made if the typical histopathological abnormalities
      (rimmed vacuoles and abnormal accumulations of proteins, in addition to
      mononuclear cell infiltrates) are present. The two women described here presented
      with myositis which was unresponsive to treatment. Patient 1 had features of non
      progressive sporadic inclusion body myositis clinically, whereas patient 2 had a
      very slowly progressive limb girdle syndrome. The cryostat sections of the first
      biopsies did not show rimmed vacuoles, even in retrospect. Only a repeated
      biopsy, 12 years after presentation in one patient and 18 years after
      presentation in the other, disclosed the typical features of sporadic inclusion
      body myositis. The initial absence of abnormal fibres probably represents a real
      absence or scarcity rather then a sampling error due to a multifocal nature of
      the histological abnormalities. It is of importance for the clinician to realise
      that some patients with myositis unresponsive to treatment, even if both clinical
      and histological features do not suggest sporadic inclusion body myositis, may
      prove to have the disease on repeated histopathological examination.

PMID- 9527160
TI  - Development of facial palsy during immunoadsorption plasmapheresis in Miller
      Fisher syndrome: a clinical report of two cases.
AB  - Immunoadsorption plasmapheresis (IAP) using a tryptophan linked gel column has
      been shown to effectively remove serum IgG anti-GQ1b antibody which may
      contribute to the pathogenesis of Miller Fisher syndrome. Two patients are
      reported on with Miller Fisher syndrome, who developed bilateral facial palsy
      during IAP using a tryptophan column, while ophthalmoplegia, ataxia, and,
      areflexia were improving. In these patients, the titre of anti-GQ1b antibodies
      was reduced. The IAP using a tryptophan column has a beneficial effect on Miller
      Fisher syndrome but may not inhibit the development of facial palsy. The
      mechanism of such a dissociated effect of IAP on Miller Fisher syndrome is
      discussed.

PMID- 9527162
TI  - Unilateral hypoglossal nerve palsy due to aneurysm of the stump of persistent
      hypoglossal artery.

PMID- 9527161
TI  - Neurofilament protein in cerebrospinal fluid: a potential marker of activity in
      multiple sclerosis.
AB  - The neurofilament protein is a major structural protein of neurons and a marker
      for axonal damage. The concentrations of the light subunit of the neurofilament
      triplet protein (NFL) in CSF were significantly increased in patients with
      relapsing-remitting multiple sclerosis compared with healthy controls (p<0.001).
      Seventy eight per cent of patients with multiple sclerosis showed increased NFL
      concentrations. Significant correlations between the NFL concentration in CSF and
      clinical indices were discerned for disability, exacerbation rate, and time from
      the start of the previous exacerbation to the time of the lumbar puncture. The
      results suggest that axonal damage occurs during relapsing-remitting multiple
      sclerosis and that the damage contributes to disability and the appearance of
      clinical exacerbations. The concentration of NFL in CSF is a potential marker of
      disease activity in multiple sclerosis and might be useful in future clinical
      trials of multiple sclerosis.

PMID- 9527163
TI  - Polymyositis and pregnancy: report of a case with three pregnancies.

PMID- 9527164
TI  - Spontaneous recovery of opsoclonus-myoclonus syndrome caused by enterovirus
      infection.

PMID- 9527165
TI  - Postpartum manifestation of a necrotising lipid storage myopathy associated with
      muscle carnitine deficiency.

PMID- 9527166
TI  - Aspecific headache during 13 years as the only symptom of idiopathic hypertrophic
      pachymeningitis.

PMID- 9527167
TI  - Proximal muscle weakness due to amyloid deposition.

PMID- 9527168
TI  - Mitochondrial myopathy with atypical subacute presentation.

PMID- 9527169
TI  - Neuroaspergillosis and brain tuberculosis in an immunocompetent patient with good
      outcome.

PMID- 9527170
TI  - Accumulation of oncofetal fibronectin in the vessels of anaplastic meningiomas.

PMID- 9527171
TI  - Repetitive sentence writing after a left anterior cerebral artery infarct.

PMID- 9527172
TI  - Peripheral neuropathies among patients with HIV infection.

PMID- 9527173
TI  - Focal vertebral artery dissection causing Brown-Sequard's syndrome.

PMID- 9527174
TI  - The familial parkinsonism locus on chromosome 4 and idiopathic Parkinson's
      disease in Japan.

PMID- 9527175
TI  - Devic type multiple sclerosis in an 81 year old woman.

PMID- 9527176
TI  - High dose intravenous methylprednisolone in cluster headache.

PMID- 9527177
TI  - Concurrent herpes simplex virus encephalitis and Creutzfeldt-Jakob disease.

PMID- 9527178
TI  - Botulinum toxin type A in the treatment of upper limb spasticity among patients
      with traumatic brain injury.

PMID- 9527179
TI  - Erdheim-Chester disease and slowly progressive cerebellar dysfunction.

PMID- 9527180
TI  - Histological surprise: callosal tuberculoma presenting as malignant glioma.

PMID- 9527181
TI  - Are circulating adhesion molecules specifically changed in cardiac surgical
      patients?
AB  - BACKGROUND: Soluble adhesion molecules are considered to be markers of
      inflammation, endothelial activation, or damage. This study was designed to
      assess whether adhesion molecules are specifically altered in patients undergoing
      cardiac surgical procedures. METHODS: Three groups of 20 patients each were
      prospectively studied: patients undergoing elective coronary artery bypass
      grafting; patients scheduled for a Whipple pancreatoduodenectomy; and patients
      undergoing elective pneumonectomy for lung cancer. Plasma levels of soluble
      adhesion molecules (endothelial leukocyte adhesion molecule-1, intercellular
      adhesion molecule-1, vascular cell adhesion molecule-1, and granule membrane
      protein 140) were measured from arterial blood samples after induction of
      anesthesia (baseline), at the end of the operation, 2 hours and 5 hours after
      operation, and on the morning of the first postoperative day. RESULTS: Duration
      of operation was longest in the group having a Whipple operation (289 +/- 50
      minutes) and did not differ between the other two groups. Plasma levels of all
      measured adhesion molecules at baseline were within normal ranges. After
      cardiopulmonary bypass, levels of adhesion molecules were significantly increased
      in the cardiac surgical patients (soluble endothelial leukocyte adhesion molecule
      1, from 38 +/- 11 ng/mL at baseline to 68 +/- 12 ng/mL; soluble intercellular
      adhesion molecule-1, from 241 +/- 50 ng/mL to 498 +/- 78 ng/mL; and granule
      membrane protein 140, from 69 +/- 12 ng/mL to 150 +/- 25 ng/mL). On the morning
      of the first postoperative day, all levels had returned to baseline except that
      of soluble vascular cell adhesion molecule-1, which was still elevated (p <
      0.05). In both the other groups, concentrations of adhesion molecules remained
      almost unchanged. CONCLUSIONS: Cardiac operation was associated with increased
      plasma levels of soluble adhesion molecules, a finding indicating endothelial
      activation or dysfunction. In contrast, in patients undergoing complex, long
      lasting abdominal or lung operations, soluble adhesion molecules remained
      unchanged. Activation of proinflammatory cascades, ischemia/reperfusion
      phenomenon, and microcirculatory dysfunction appear to be the most likely reasons
      for this difference between groups. Whether modulation of adhesion molecules may
      influence organ function after cardiopulmonary bypass remains to be elucidated in
      further studies.

PMID- 9527182
TI  - Minimally diluted tepid blood cardioplegia.
AB  - BACKGROUND: To evaluate the effects of minimally diluted tepid blood
      cardioplegia, a prospective, randomized study was undertaken. METHODS: Thirty
      seven patients undergoing isolated primary coronary artery bypass grafting were
      randomized to receive standard 4:1 diluted tepid blood cardioplegia (4:1 group, n
      = 18) or minimally diluted tepid blood cardioplegia (Mini group, n = 19).
      Cardioplegic solution was delivered in an intermittent antegrade fashion in both
      groups. Myocardial oxygen and lactate metabolism, release of the MB isoenzyme of
      creatine kinase and thiobarbituric acid reactive substances, and cardiac function
      were measured during and after the operation. RESULTS: Myocardial oxygen
      consumption was significantly greater and lactate release was significantly lower
      in the Mini group than in the 4:1 group during cardioplegia. Minimally diluted
      blood cardioplegia resulted in more prompt resumption of lactate extraction,
      lower levels of release of the myocardial-specific isoenzyme of creatine kinase
      and thiobarbituric acid reactive substances during reperfusion, and better
      postoperative left ventricular function compared with the standard 4:1
      cardioplegia. CONCLUSIONS: Minimally diluted tepid blood cardioplegia may provide
      superior myocardial protection than the standard 4:1 dilution technique by
      optimizing the aerobic environment through an increase in oxygen supply during
      intermittent cardioplegia.

PMID- 9527183
TI  - Infectious mediastinitis after cardiac operations: computed tomographic findings.
AB  - BACKGROUND: Infectious mediastinitis after cardiac operations is of great concern
      to cardiac surgeons because of its poor prognosis. Prompt surgical interventions
      such as debridement and irrigation are the key to treatment of infectious
      mediastinitis. METHODS: We surveyed retrospectively the cases of 722 consecutive
      cardiac surgery patients at our hospital. Mediastinitis developed in 21 patients
      after the cardiac operation. We performed computed tomography in 11 of these
      patients before resternotomy and in 10 patients as the control 2 to 3 weeks after
      the cardiac operation. RESULTS: Mediastinal soft tissue swelling was seen in 7
      patients, bilateral pleural effusion was found in 9 patients, sternal dehiscence
      or sternal erosion was observed in 8 patients, and subcutaneous fluid
      accumulation was found in 7 of the mediastinitis group. Unilateral pleural
      effusion was seen in 6 and bilateral effusion in 1, and mediastinal soft tissue
      swelling was seen in 1 patient of the control group. CONCLUSIONS: Our study
      showed that mediastinal soft tissue mass combined with bilateral pleural effusion
      can be a characteristic computed tomography finding in poststernotomy infectious
      mediastinitis, and that chest computed tomography is more sensitive to detecting
      sternal dehiscence, sternal erosion, and subcutaneous fluid accumulation.

PMID- 9527184
TI  - Value of reversed saphenous vein in minimally invasive direct coronary artery
      bypass graft procedures.
AB  - BACKGROUND: Minimally invasive direct coronary artery bypass graft procedures are
      gaining acceptance for revision as well as primary coronary revascularization.
      When suitable, the left and right internal mammary arteries are preferred as
      bypass conduits; in other cases, the greater saphenous vein, used for standard
      coronary artery bypass graft procedures, may be useful to revascularize coronary
      artery branches during minimally invasive direct coronary artery bypass graft
      procedures. METHODS: We used the greater saphenous vein on three occasions during
      minimally invasive direct coronary artery bypass graft procedures (1) to
      revascularize the left anterior descending coronary artery by anastomosis to the
      left axillary artery in the infraclavicular region, (2) as an extension to the
      left internal mammary artery to reach the left anterior descending coronary
      artery, and (3) as a bridge from the splenic artery to bypass the distal right
      coronary artery. RESULTS: Postoperatively, all 3 patients had relief from
      symptoms of coronary artery insufficiency and none has been readmitted to the
      hospital with symptoms. Angiography or thallium studies were not performed to
      confirm graft patency because all patients were elderly and the risks of these
      procedures were considered to outweigh their potential benefit. CONCLUSIONS: The
      greater saphenous vein is a potential bypass conduit for use in minimally
      invasive direct coronary artery bypass graft procedures as well as for coronary
      artery bypass graft procedures.

PMID- 9527186
TI  - Temporary atrial electrode for the treatment of supraventricular tachycardia
      after cardiac operations.
AB  - BACKGROUND: Supraventricular tachycardia is a common postoperative complication
      early after cardiac operations. A temporary atrial patch electrode for low-energy
      atrial defibrillation was developed in 1992 and subsequently tested. METHODS: The
      electrode first was tested and removed intraoperatively during open heart
      operations in 10 patients (phase I). After the intraoperative testing, the
      temporary atrial patch electrode was implanted in 20 patients for postoperative
      termination of spontaneous episodes of supraventricular tachycardia (phase II).
      When supraventricular tachycardia occurred, biphasic shocks (1.2 to 5 J) were
      applied and the atrial defibrillation thresholds were measured. RESULTS: In phase
      I, the mean intraoperative atrial defibrillation threshold was 1.6 +/- 1.4 J,
      with a mean shock impedance of 64 +/- 7.3 omega. In phase II, 6 of 20 patients
      (30%) had 7 episodes of atrial fibrillation (n = 6) and atrial flutter (n = 1)
      after operation. In 5 patients, the supraventricular tachycardia could be
      converted to a sinus (n = 5) or normofrequent atrioventricular rhythm (n = 1).
      The mean postoperative defibrillation threshold was 2.7 +/- 2.1 J, with a mean
      shock impedance of 50.2 +/- 6.8 omega. CONCLUSIONS: The temporary atrial patch
      electrode allows low-energy defibrillation of episodes of atrial fibrillation. It
      may serve as an alternative therapeutic option for the treatment of
      supraventricular tachycardia.

PMID- 9527185
TI  - Inflow valve regurgitation during left ventricular assist device support may
      interfere with reverse ventricular remodeling.
AB  - BACKGROUND: Left ventricular assist devices have been reported previously to
      reverse ventricular remodeling in patients with dilated cardiomyopathy. In
      patients with prolonged mechanical support, structural failure of the left
      ventricular assist device inflow valve can cause regurgitation into the left
      ventricle, which may affect adversely this process. METHODS: Left ventricular end
      diastolic pressure-volume relation of hearts explanted from 8 patients with left
      ventricular assist device and 8 control subjects with idiopathic cardiomyopathy
      was determined ex vivo at the time of transplantation. RESULTS: Duration of
      mechanical support ranged from 210 to 276 days (mean +/- standard deviation = 283
      +/- 76 days) in 3 patients with inflow valve regurgitation versus 100 to 155 days
      (132 +/- 22 days) in 5 patients without (p = 0.005). The end-diastolic pressure
      volume relation of all hearts supported mechanically was shifted to the left
      toward normal controls. This effect was markedly attenuated in patients with
      inflow valve regurgitation. CONCLUSIONS: Mechanical assistance can cause reverse
      remodeling in patients with dilated cardiomyopathy as evidenced by the shift in
      the end-diastolic pressure-volume relation curve to the left. Inflow valve
      failure, associated with prolonged support, can attenuate changes in left
      ventricular structure and dimension. Ineffective pressure and volume unloading
      may explain these observations.

PMID- 9527187
TI  - Bradycardia induced by intravascular versus direct stimulation of the vagus
      nerve.
AB  - BACKGROUND: Electrical stimulation of the parasympathetic nervous system results
      in slowing of the heart. We sought to determine whether cardiac vagal efferent
      axons can be stimulated adequately to induce bradycardia without disturbing the
      integrity of the thorax. METHODS: Cardiodepressor effects elicited by direct
      stimulation of a vagus nerve in anesthetized dogs and pigs were compared with
      those generated when the same nerve was stimulated indirectly through bipolar
      electrodes placed in the adjacent superior vena cava. RESULTS: The heart rate of
      dogs decreased by about 80% when electrical stimuli were delivered to the right
      thoracic vagus at the level of the thoracic outlet through bipolar electrodes
      placed either in the adjacent superior vena cava (intravascular method) or
      directly on the nerve (direct method). Maximal responses were achieved with 10-V,
      5-ms, and 20-Hz stimuli. In anesthetized pigs, similar bradycardia occurred when
      the right cervical vagus or the right cranial thoracic vagus was stimulated
      either directly or indirectly through the intravascular method. Atrial
      dysrhythmias occurred when the stimulating electrodes were placed by either
      method within 1 cm of the right atrium in both animal models. CONCLUSIONS:
      Controlled bradycardia can be induced during operation without the risk of
      generating cardiac dysrhythmias using electrical stimuli (10 V, 5 ms, and 10 to
      20 Hz) delivered to the right cervical vagus nerve or the right cranial thoracic
      vagus nerve through adjacent intravascular electrodes.

PMID- 9527188
TI  - Transition from cardiopulmonary bypass to the HeartMate left ventricular assist
      device.
AB  - BACKGROUND: Safe transition from cardiopulmonary bypass to the HeartMate left
      ventricular assist device without periods of low output, air emboli, or injury to
      the right ventricle is vital to its successful implantation. A right atrial-to
      left ventricular shunt has been developed to purge quickly and completely all air
      from the system and prevent its reentry, as well as to assist the right ventricle
      during the transition from cardiopulmonary bypass to the HeartMate. METHODS: From
      January 1994 through July 1996, we used an extracorporeal membrane oxygenation
      right atrial-to-left ventricular shunt during 17 HeartMate implantations in 16
      patients. The shunt consists of the existing right atrial two-stage cannula, the
      bypass circuit, and a separate aortic line that fills the left ventricle using a
      21F cannula in the lateral ventricular wall. Air is monitored in the heart and
      aorta using transesophageal echocardiography. RESULTS: Ten of the 16 patients are
      living and 8 have undergone transplantation. Two patients are still using the
      device and are awaiting transplantation. None of the patients have experienced
      postoperative neurologic events suggestive of air emboli. CONCLUSIONS: The
      extracorporeal membrane oxygenation right atrial-to-left ventricular shunt is
      simple and inexpensive to construct. It provides for a smoother and safer
      transition from cardiopulmonary bypass to the HeartMate left ventricular assist
      device.

PMID- 9527189
TI  - Gene transfer into the donor heart during cold preservation for heart
      transplantation.
AB  - BACKGROUND: Ex vivo gene transfer to heart grafts may hold promise as a means of
      changing alloreactivity or xenoreactivity after transplantation. However, it
      remains to be determined how effectively gene transfer can be accomplished within
      a short time in cold-stored grafts that are ready to be transplanted. METHODS: We
      performed an experimental study using a replication-defective adenovirus
      (Adex1CALacZ) encoding the Escherichia coli beta-galactosidase (beta-gal) gene to
      perform gene transfer to heart grafts awaiting transplantation. Thirty hearts of
      Wistar rats were removed and their coronary arteries were perfused with
      University of Wisconsin solution containing 1 x 10(9), 1 x 10(10), or 1 x 10(11)
      plaque-forming units of the recombinant adenovirus at 4 degrees C for 60 minutes.
      As a control, other hearts were perfused with University of Wisconsin solution
      with an adenoviral vector that did not contain the beta-gal gene (Adex1w1) for
      the same period. After perfusion, the grafts were implanted in the necks of
      syngeneic adult rats. The grafts were removed each week after transplantation and
      their expression of beta-gal was assessed by 5-bromo-4-chloro-3-indoyl-beta-D
      galactoside staining. RESULTS: Successful gene transfer and expression of the
      beta-gal gene were demonstrated in adenovirus-perfused hearts. Gene transfer
      occurred preferentially in the cardiomyocytes over the endothelial cells and
      smooth muscle cells of the coronary vessels. In hearts perfused with 1 x 10(9)
      plaque-forming units of the adenovirus, gene expression persisted for 4 weeks
      after transfer, but it diminished gradually and was minimal by day 28. Histologic
      analyses revealed slight inflammatory reactions in the myocardium. In hearts
      perfused with 1 x 10(10) and 1 x 10(11) plaque-forming units of the adenovirus,
      beta-gal diminished 3 weeks after transplantation and a prominent infiltration of
      leukocytes was recognized in the myocardium. CONCLUSIONS: This study demonstrated
      that the cardiomyocytes of heart grafts express an exogenous gene product after
      adenovirus-mediated gene transfer under hypothermic preservation conditions.
      However, immune or inflammatory reactions to recombinant adenoviruses must be
      taken into account when a large number of adenoviruses are injected into the
      coronary arteries.

PMID- 9527190
TI  - Jugular venous bulb oxygen saturation depends on blood pressure during
      cardiopulmonary bypass.
AB  - BACKGROUND: Central nervous system dysfunction after cardiopulmonary bypass is
      frequent and can be caused by inadequate cerebral perfusion and oxygenation.
      METHODS: To test the effectiveness of cerebral autoregulation during
      cardiopulmonary bypass, we induced changes in the cerebral perfusion pressure by
      administering phenylephrine during moderate (29 degrees C) hypothermia. Using the
      Fick principle, we calculated relative changes in cerebral blood flow from
      changes in the jugular venous bulb oxygen saturation. RESULTS: Increasing the
      cerebral perfusion pressure (from 47 +/- 8.2 to 93 +/- 16 mm Hg) induced
      increases in the jugular venous bulb oxygen saturation by 4.9% and a calculated
      increase in the cerebral blood flow by 19.9%, strongly suggesting impaired
      cerebral autoregulation. CONCLUSIONS: Because cerebral autoregulation is impaired
      during cardiopulmonary bypass, phenylephrine is effective in increasing the
      cerebral blood flow and may contribute to the prevention of postoperative
      neurologic dysfunction, especially in patients who have a low jugular venous bulb
      oxygen saturation.

PMID- 9527191
TI  - Left anterior descending endarterectomy and internal thoracic artery bypass for
      diffuse coronary disease.
AB  - BACKGROUND: The risk and efficacy of using an arterial conduit to bypass an
      endarterectomized coronary artery remain incompletely defined. To address this
      question we analyzed retrospectively 74 patients from 1989 to 1994 in whom bypass
      grafting using the left internal thoracic artery to an endarterectomized left
      anterior descending artery was performed. METHODS: There were 60 men and 14 women
      with a mean age of 60.1 +/- 8.6 years. Of this cohort, 55 patients (74.3%) had a
      previous infarction, 18 (24.3%) were diabetic, and 5 (6.7%) had reoperations; 25
      patients (34%) had a totally occluded left anterior descending artery and the
      average ejection fraction was 45%. Each patient had 2.95 +/- 0.52 grafts with 48
      patients (65%) requiring multiple endarterectomies. The average length of the
      endarterectomized segment was 3.1 +/- 1.6 cm. Average anoxia time was 49 +/- 13
      minutes. Postoperatively 19 patients (25.6%) required intraaortic balloon and 18
      (24.3%) required inotropic support. Perioperative infarction in the left anterior
      descending artery distribution occurred in 5 patients (6.7%). RESULTS: There were
      3 (4.0%) early and 4 (5.4%) late deaths at a mean follow-up of 36 +/- 16 months.
      Recurrent angina was present in 9 patients (14.7%). Actuarial 5-year survival was
      84.5%. Angiographic follow-up obtained in 23 patients (37.4%) demonstrated 74%
      anastomotic patency, with good distal run-off in 13 (65%). The anterior segmental
      wall motion was preserved. CONCLUSIONS: The use of the left internal thoracic
      artery bypass and adjunctive left anterior descending artery endarterectomy to
      expand the scope of myocardial revascularization in carefully selected
      circumstances appears to be beneficial.

PMID- 9527192
TI  - Effect of assisted circulation on left ventricular performance in a canine model.
AB  - BACKGROUND: Little is known about left ventricular performance during
      venoarterial bypass and left heart bypass (LHB) after cross-clamping the
      descending thoracic aorta. We evaluated the effects of venoarterial bypass and
      LHB on ventricular load optimization and left ventricular work efficiency.
      METHODS: We used the left ventricular conductance catheter and a micromanometer
      in 7 anesthetized mongrel dogs. We assessed preload by the end-diastolic volume,
      afterload by the effective arterial elastance, and left ventricular contractile
      properties by the slope of the end-systolic pressure-volume relationship. In
      addition, optimal ventricular arterial coupling (ratio of effective arterial
      elastance to slope of end-systolic pressure-volume relationship) and left
      ventricular work efficiency (ratio of external work to pressure-volume area) were
      calculated. RESULTS: The decrease in preload was much greater with LHB than
      venoarterial bypass. There were no significant differences in afterload and left
      ventricular contractility between venoarterial bypass and LHB. The ventricular
      arterial coupling during LHB was near 0.50 (0.69 +/- 0.16) in the "best heart"
      condition (effective arterial elastance = slope of end-systolic pressure-volume
      relationship/2), whereas the work efficiency during LHB was at maximum (0.73 +/-
      0.12). CONCLUSIONS: We conclude that LHB has a more beneficial effect on left
      ventricular performance after cross-clamping of the descending thoracic aorta.

PMID- 9527193
TI  - High-dose epsilon-aminocaproic acid versus aprotinin: antifibrinolytic efficacy
      in first-time coronary operations.
AB  - BACKGROUND: The antifibrinolytic efficacy of a high-dose regimen of epsilon
      aminocaproic acid (epsilon-ACA) was compared with aprotinin in first-time
      coronary operations. METHODS: In a prospective, double-blinded, randomized study,
      20 patients received high-dose epsilon-ACA (10 g both as a loading and
      cardiopulmonary bypass priming dose, 2.5 g/h until 4 hours after protamine), and
      another 20 patients received aprotinin (2 x 10(6) KIU [280 mg] for loading and
      priming, 0.5 x 10(6) KIU/h [70 mg/h]). Ten untreated patients served as controls.
      RESULTS: Both agents reduced postoperative levels of thrombin/antithrombin III
      complexes, D-dimers, fibrin degradation products, free plasma hemoglobin (epsilon
      ACA versus aprotinin, p = not significant; p < 0.05 versus controls), and amount
      of retransfused autologous blood (p < 0.001). Epsilon-ACA increased, aprotinin
      suppressed antiplasmin-plasmin complex generation (epsilon-ACA versus controls, p
      < 0.02; epsilon-ACA versus AP, p < 0.0001). For 4 hours after discontinuation,
      more chest drainage occurred with epsilon-ACA than aprotinin (137 +/- 90 mL
      versus 62 +/- 29 mL; means +/- standard deviation; p < 0.02). Cumulative 12-hour
      drainage was similar for aprotinin (391 +/- 220 mL) and epsilon-ACA (582 +/- 274
      mL), but higher without inhibitor (1,091 +/- 541 mL; p < 0.001 versus drugs).
      Postoperatively, aprotinin was associated with the lowest autologous
      retransfusion incidence and highest hematocrits (p < 0.01 versus epsilon-ACA).
      Homologous transfusion exposures did not differ. CONCLUSIONS: In first-time
      coronary operations, higher postoperative hematocrit and less shed blood
      retransfusion constitute only subtle advantages of aprotinin over high-dose
      epsilon-ACA.

PMID- 9527194
TI  - Aprotinin and dipyridamole for the safe reduction of postoperative blood loss.
AB  - BACKGROUND: Aprotinin (APR) reduces postoperative blood loss but may induce
      thrombosis. Dipyridamole (DIP) limits platelet aggregation and may reduce the
      thrombotic complications associated with APR. METHODS: To evaluate the safety and
      effectiveness of combined APR and DIP, we undertook a prospective randomized
      trial in patients undergoing cardiac operations. Patients were stratified
      according to risk for bleeding (low or high), and received either DIP with
      placebo (DIP group; n = 59) or DIP with APR (DIP + APR group; n = 56). Blood
      samples were obtained for the measurement of hematologic and biochemical
      parameters. Blood loss and transfusion requirements were documented
      postoperatively. RESULTS: Postoperative blood loss and transfusion requirements
      were significantly lower in the DIP + APR group at 6, 12, and 24 hours after
      bypass (p < 0.01). No significant differences were found between groups in the
      incidence of perioperative mortality (DIP, 0%; DIP + APR, 3%), myocardial
      infarction (DIP, 0%; DIP + APR, 3%), stroke (DIP, 1%; DIP + APR, 1%), or
      potential thrombotic events (death, myocardial infarction, and stroke: DIP, 2%;
      DIP + APR, 5%). In addition, these rates did not differ from those of
      nonparticipating matched control patients. CONCLUSIONS: Administration of both
      drugs simultaneously was more effective than DIP alone in reducing postoperative
      blood loss. A platelet inhibitor may be required to reduce the thrombotic
      complications associated with APR. Further studies evaluating graft patency and
      perioperative ischemia are necessary to confirm the potential benefits of the
      combination of a platelet inhibitor and APR.

PMID- 9527195
TI  - Renal effects of alpha-ketoglutarate early after coronary operations.
AB  - BACKGROUND: Alpha-ketoglutarate (alpha-KG) is a Krebs cycle intermediate and the
      carbon skeleton of glutamate. Alpha-ketoglutarate has provoked interest in heart
      surgery because of its proposed critical role in myocardial metabolism. This
      study investigates the role of alpha-KG in renal function after cardiac surgical
      procedures. METHODS: Twenty-two patients with normal preoperative renal function
      were included in a prospective, randomized, and controlled study. Eleven patients
      received intravenous infusion of 30 g alpha-KG/hour after the operation.
      Measurements were performed before operation, immediately after operation, and
      after 30 minutes of alpha-KG infusion. RESULTS: Renal blood flow was higher
      during alpha-KG infusion, 297% +/- 97% (of preoperative value), than in controls,
      125% +/- 20% (p < 0.05). Filtration fraction was lower (12.3% +/- 0.05% versus
      17.2% +/- 1.1%, p < 0.01), which prevented a significant difference in glomerular
      filtration rate. The renal arteriovenous differences of lactate, glutamate,
      glutamine, and glycine changed toward a net release during alpha-KG infusion.
      CONCLUSIONS: Infusion of alpha-KG enhances renal blood flow early after coronary
      surgical procedures in patients with normal renal function. The mechanism is
      unclear, but could be associated with primarily metabolic effects, and may
      potentially convey a beneficial effect for renal function.

PMID- 9527196
TI  - Platelet and neutrophil activation during cardiac surgical procedures: impact of
      cardiopulmonary bypass.
AB  - BACKGROUND: Platelet and neutrophil activation plays a crucial role in
      reperfusion injury. To determine whether platelet and neutrophil activation
      occurs in the coronary circulation after cold cardioplegic arrest and
      reperfusion, we studied 22 patients undergoing coronary artery bypass or valve
      procedures, or both procedures. METHODS: Blood was sampled from the coronary
      sinus and the radial artery (A) before bypass; (B) immediately after cross-clamp
      release; and (C) 5 minutes after cross-clamp release; and was analyzed for
      surface markers of platelet (CD62P) and neutrophil (CD11b) activation. RESULTS:
      During bypass, platelet activation increased significantly (p < 0.01) over
      prebypass values, but no difference was seen between arterial and coronary sinus
      samples. Neutrophil activation also increased significantly (p < 0.001) during
      bypass, but there was no difference between arterial and coronary sinus samples.
      CONCLUSIONS: Cellular activation occurs locally in the coronary circulation
      during bypass, but no more so after cold cardioplegic arrest and reperfusion.

PMID- 9527197
TI  - Re-replacement for prosthetic valve dysfunction: analysis of long-term results
      and risk factors.
AB  - BACKGROUND: Prosthetic heart valve re-replacement still remains a challenging
      situation. Although some studies have examined the early results, the long-term
      survival has not yet been well analyzed. The aim of this study was to detect the
      factors that affect the long-term outcome of operation. METHODS: Between April
      1964 and September 1996, 231 prosthetic valve re-replacements were performed
      including 16 cases of third valve replacement. There were 100 men and 131 women
      with a mean age of 47 +/- 14 years. RESULTS: The actuarial survival rate was 65%
      +/- 4% at 5 years and 41% +/- 7% at 10 years. Multivariate analysis revealed that
      New York Heart Association class IV and left ventricular ejection fraction were
      found to be independent predictors of late death. CONCLUSIONS: Our study showed
      that advanced New York Heart Association functional class and lower left
      ventricular ejection fraction were found to be independent predictors of late
      death. If operation is performed before patients reach such a deteriorated
      condition, long-term results are excellent.

PMID- 9527198
TI  - Early results of transmyocardial revascularization with a holmium laser.
AB  - BACKGROUND: Transmyocardial laser revascularization (TMLR), a surgical technique
      designed to improve perfusion in the ischemic myocardium by creating transmural
      channels, has been performed thus far using a carbon dioxide laser, with
      apparently gratifying early results. We have investigated clinically TMLR using a
      holmium laser as sole therapy for patients with coronary artery disease that is
      not amenable to traditional treatment such as coronary artery bypass grafting or
      percutaneous transluminal coronary angioplasty. METHODS: From November 1995 to
      December 1996, 16 patients underwent TMLR using a holmium laser. Their mean age
      was 68 +/- 6 years and 75% were men. Previous coronary artery bypass grafting or
      percutaneous transluminal coronary angioplasty had been performed in 81% and 31%
      of the patients, respectively. Before operation, their mean anginal class was 3.4
      +/- 0.5 and their mean left ventricular ejection fraction was 0.49 +/- 0.06. Six
      patients had unstable angina. RESULTS: There were no operative deaths. The mean
      duration of TMLR was 27 +/- 13 minutes and the mean duration of the entire
      operation was 120 +/- 40 minutes. There were no major postoperative complications
      and the mean hospital stay was 8 +/- 4 days. There were 2 late deaths, 1 that
      occurred 40 days after TMLR as a result of stroke and 1 that occurred 4 months
      after TMLR as a result of myocardial infarction. Current survivors have been
      followed up for a mean of 10 +/- 4 months (range, 3 to 15 months), with 7
      patients followed up for 1 year. At last follow-up, the mean anginal class had
      decreased to 1.8 +/- 0.7 (p = 0.001) and the patients had increased exercise
      tolerance and a reduced number of hospitalizations. However, no statistically
      significant changes in the percentage of segments with fixed or reversible
      ischemia and no statistically significant differences in the viability scores of
      lased and nonlased segments were observed. CONCLUSIONS: Transmyocardial laser
      revascularization using a holmium laser is a simple technique with low operative
      risk and low morbidity. Early results confirm that clinical improvement is
      obtained in most patients, although significant changes in myocardial perfusion
      are not evident in the short term.

PMID- 9527199
TI  - Intima-adventitia apposition in end-to-side arterial anastomosis: an experimental
      study in the pig.
AB  - BACKGROUND: To prevent ischemic complications during coronary bypass grafting on
      the beating heart, a nonocclusive distal anastomosis technique is needed. One
      recently developed nonocclusive technique requires apposition of the intima of
      the graft to the adventitia of the recipient artery, in contrast to current
      surgical practice, which dictates apposition of both intimas. METHODS: To compare
      the sole effect of intima-adventitia apposition (n = 18) versus traditional
      intima-intima apposition (n = 18), we investigated radiolabeled platelet
      deposition and histomorphologic aspects of vascular wall healing quantitatively
      in a porcine carotid artery bypass graft model. Both groups were evaluated at 2
      hours, 2 days, or 4 weeks. RESULTS: Within the first 2 hours, 3 of 6 pigs with
      intima-adventitia apposition exhibited cyclic flow reductions as a result of
      massive mural thrombosis. After intima-adventitia apposition, the number of
      deposited platelets was significantly higher compared with intima-intima
      apposition, 147.1 +/- 73.0 x 10(6) and 4.6 +/- 1.0 x 10(6) platelets/cm2 (mean +/
      standard error of the mean), respectively (p = 0.03). At 2 days, the suture line
      was covered with small mural thrombi, whereas no thrombi were found after intima
      intima apposition. At 4 weeks, intimal hyperplasia at heel and toe was not
      significantly different from that with intima-intima apposition. CONCLUSIONS:
      Despite thrombotic phenomena in the early phase, intima-adventitia apposition
      yielded a patent anastomosis with a small intimal hyperplasia response.

PMID- 9527200
TI  - Activation of coagulation and fibrinolysis during cardiothoracic operations.
AB  - BACKGROUND: During open cardiac operations using cardiopulmonary bypass, there is
      activation of coagulation and fibrinolysis. We assessed the separate
      contributions of the surgical procedure itself and cardiopulmonary bypass to
      this, by studying sequential samples from patients undergoing routine open
      cardiac operations or thoracic operations without cardiopulmonary bypass.
      METHODS: Activation of coagulation and the extent of fibrinolysis were measured
      from sequential samples obtained before the operation to 48 hours after the
      operation for 7 thoracic patients and 8 cardiac patients. RESULTS: In the
      thoracic group operation length was shorter (p = 0.002), and there was no
      significant increase in thrombin-antithrombin III complexes or D-dimers until 24
      hours postoperatively. In contrast, there was a highly significant increase in
      thrombin-antithrombin III complexes (p = 0.0043) and D-dimer levels (p = 0.009)
      during cardiopulmonary bypass. The increase in fibrinolytic activity was caused
      by an increase in tissue plasminogen activator (p = 0.013). At 48 hours
      postoperatively, the cardiac patients had a more hypercoagulable state than
      thoracic patients with significantly higher levels of thrombin-antithrombin III
      complexes (p = 0.041) and plasminogen activator inhibitor-1 activity (p =
      0.0033). CONCLUSIONS: This study suggests the major activation of coagulation and
      fibrinolysis seen during cardiac operations is caused by the use of
      cardiopulmonary bypass.

PMID- 9527201
TI  - Granulocyte elastase release and pulmonary hemodynamics in patients with atrial
      septal defect.
AB  - BACKGROUND: In patients with increased pulmonary artery pressure, the pulmonary
      vascular endothelium is morphologically and functionally abnormal and may be
      vulnerable to neutrophil-mediated injury induced by cardiopulmonary bypass (CPB).
      We investigated the relation between levels of granulocyte elastase (GEL),
      interleukin-6, or interleukin-8 after CPB and preoperative pulmonary hemodynamics
      or changes in pulmonary function after the operation. METHODS: We measured plasma
      levels of GEL, interleukin-6, and interleukin-8 before and after CPB in patients
      who underwent closure of an atrial septal defect. Preoperative and postoperative
      respiratory index were evaluated. Preoperative pulmonary hemodynamics were
      determined within 1 month before the operation. RESULTS: The level of GEL rose
      significantly after CPB from baseline (164.8 +/- 81.3 versus 819.4 +/- 320.3
      microg/L; p < 0.01). Levels of interleukin-6 and interleukin-8 showed no
      significant changes after CPB. Peak level of GEL was significantly correlated
      with preoperative systolic pulmonary artery pressure (r = 0.76; p = 0.017), mean
      pulmonary artery pressure (r = 0.75; p = 0.021) and pulmonary-to-systemic
      arterial pressure ratio (r = 0.77; p = 0.016), but not with the hemodynamic
      variables for pulmonary blood flow or pulmonary resistance. Moreover, the value
      of (postoperative respiratory index - preoperative respiratory
      index)/preoperative respiratory index was positively correlated with the peak
      level of GEL (r = 0.72; p = 0.030). CONCLUSIONS: The increase in GEL level after
      CPB is proportional to the increase in preoperative pulmonary artery pressure,
      which may cause the accordant pulmonary vascular damage.

PMID- 9527202
TI  - Reduction of allogeneic blood transfusions after open heart operations by
      lowering cardiopulmonary bypass prime volume.
AB  - BACKGROUND: Despite recent advances in blood conservation techniques, up to 30%
      to 80% of patients undergoing open heart operations require allogeneic blood
      transfusions. A prospective, randomized study was performed to test the effect of
      lowering cardiopulmonary bypass prime volume (as an additional component of an
      integrated blood conservation strategy) on clinical outcome and allogeneic blood
      transfusion. METHODS: One hundred fourteen patients undergoing open heart
      operations were randomized to either full prime (FP) volume (1,400 mL of
      Plasmalyte solution) or reduced prime (RP) volume (600 to 800 mL). The reduction
      of prime volume was achieved by slowly draining the cardiopulmonary bypass
      circuit into a cell-saving device before the initiation of bypass. Firm
      transfusion thresholds were observed. RESULTS: There were no significant
      differences between the groups with respect to baseline characteristics, body
      surface area, type and urgency of the procedures, perfusion technique, and
      hematologic profile. Mortality (FP, 1.7%; RP, 0%; p approximately 1.0) and
      overall morbidity (FP, 28.1%; RP, 22.8%; p = 0.53) were similar. However,
      transfusion requirements were significantly lower in the RP group: total donor
      exposure, 3.8 +/- 10.1 versus 1.0 +/- 2.4 units (p = 0.044); percentage of
      patients transfused, 54% (n = 31) versus 35% (n = 20) (p = 0.036). Twenty-four
      hour chest tube drainage was similar: 455 +/- 223 mL for FP versus 472 +/- 173 mL
      for RP (p = 0.66). The lowest hematocrit on bypass was significantly higher in
      the RP group: 29.3% +/- 4% versus 26.3% +/- 5.3% (p = 0.009). CONCLUSIONS:
      Lowering cardiopulmonary bypass prime volume resulted in a significant decrease
      in allogeneic blood product use. Because postoperative 24-hour chest tube
      drainage was similar in both groups, and hematocrit during bypass was higher in
      the RP group, the reduction in allogeneic blood transfusions appears to be
      related to a decrease in prime-induced hemodilution. This technique is effective,
      simple, and safe. It therefore should be strongly considered for patients
      undergoing operations using normothermic or near-normothermic cardiopulmonary
      bypass who are at high risk for allogeneic blood transfusion.

PMID- 9527203
TI  - Angiographic follow-up of internal thoracic artery for free bypass grafting.
AB  - BACKGROUND: The use of free internal thoracic artery (ITA) grafts in patients
      with smaller body surface areas has been questioned because of technical
      difficulties and inadequate graft flow. METHODS: To evaluate postoperative
      changes in the diameter of free ITA grafts, we performed coronary angiography
      immediately after coronary artery bypass grafting and then again at a mean of 42
      +/- 6 months later. In 20 consecutively treated patients, 21 free ITAs were used
      as bypass conduits. Two ITA grafts that were patent at the time of the first
      angiography had closed at the second angiography. Postoperative changes in ITA
      graft diameter were measured in the 19 patent ITA grafts. RESULTS: At the first
      angiography, the mean diameters of the proximal, middle, and distal ITA grafts
      were 2.28 +/- 0.45 mm, 2.34 +/- 0.39 mm, and 2.12 +/- 0.38 mm, respectively. At
      the second angiography, the mean diameters of the proximal, middle, and distal
      ITA grafts were 2.85 +/- 0.50 mm, 2.89 +/- 0.53 mm, and 2.72 +/- 0.53 mm,
      respectively. All segments of the ITA grafts had dilated significantly between
      the first and second angiographic evaluations (p < 0.01). The percentage change
      in graft diameter was greater when the initial ITA diameter was less than 2.3 mm
      (32.0% +/- 28.0%) than when it was 2.3 mm or more (18.8% +/- 11.3%) (p < 0.05).
      CONCLUSIONS: The postoperative increase in free ITA graft diameter depends on
      coronary blood flow requirements.

PMID- 9527204
TI  - Aneurysm of sinus of Valsalva dissecting into interventricular septum.
AB  - BACKGROUND: Dissection of interventricular septum by aneurysm of the sinus of
      Valsalva is extremely rare. We present our experience with the management of 10
      patients with this condition. METHODS: Ten patients with aneurysm of the sinus of
      Valsalva dissecting into the interventricular septum were managed at All India
      Institute of Medical Sciences, New Delhi, between May 1987 and September 1996.
      Conduction abnormalities and aortic insufficiency dominated the clinical picture.
      Eight patients underwent surgical repair. Two patients refused operation, and
      only permanent pacemaker implantation was done for complete heart block in both
      these patients. RESULTS: There was no hospital mortality. Follow-up ranged from 1
      to 9 years. There was one late death due to carcinoma of the larynx, and 1
      patient required reoperation for persistent aortic insufficiency. All other
      patients who underwent operation are in New York Heart Association functional
      class I. CONCLUSIONS: We recommend surgical repair of this condition to deal with
      aortic regurgitation and to avoid the potential risk of rupture, thromboembolism,
      and infective endocarditis. However, surgical repair offers no guarantee against
      arrhythmias and conduction abnormalities.

PMID- 9527205
TI  - Intraaortic balloon pump in open heart operations: 10-year follow-up with risk
      analysis.
AB  - BACKGROUND: The intraaortic balloon pump (IABP) is the primary mechanical device
      used for perioperative cardiac failure. METHODS: We analyzed the prognostic
      predictors and long-term survival of 344 patients undergoing cardiac operations
      who required the perioperative use of an IABP at our institution from January
      1980 to December 1989. Hospital survivors (163 patients) were followed up for a
      mean of 7.45 years (range, 1 month to 15.3 years); cumulative follow-up included
      1,167 patient-years. RESULTS: The early mortality rate was 52.6% (181 patients).
      From parameters available at the time of IABP insertion, logistic regression
      analysis identified preoperative serum creatinine level, left ventricular
      ejection fraction, perioperative myocardial infarction, timing of IABP insertion,
      and indication for operation as independent predictors of early (30-day) death (p
      < 0.05). Cox regression analysis of hospital survivors identified timing of IABP
      insertion, perfusion time, and preoperative serum creatinine level as independent
      prognostic factors for late death (p < 0.05), whereas patient age was only
      marginally significant (p < 0.06). There was no association between IABP-related
      complications and death. Survival analysis demonstrated a 10-year actual survival
      rate of 22.04% +/- 0.023%, with 57 patients still at risk and significantly
      improved survival among those who received an IABP before operation (p < 0.02).
      CONCLUSIONS: The early mortality rate in patients who received an IABP was high.
      Hospital survivors had a relatively good long-term prognosis. The significantly
      better short- and long-term survival of patients who received an IABP before
      operation may justify more liberal preoperative use of the IABP in high-risk
      patients.

PMID- 9527206
TI  - Prospective, randomized clinical study of ischemic preconditioning as an adjunct
      to intermittent cold blood cardioplegia.
AB  - BACKGROUND: Ischemic preconditioning has been shown to be beneficial to
      myocardial preservation in a variety of models. This study was performed to
      determine whether ischemic preconditioning can ameliorate the postischemic
      myocardial dysfunction often seen in patients undergoing open heart operations.
      METHODS: Seventy patients were prospectively randomized to receive or not receive
      ischemic preconditioning before intermittent cold blood cardioplegic arrest.
      Ischemic preconditioning was induced by 1 minute of aortic cross-clamping
      followed by 5 minutes of reperfusion during normothermic cardiopulmonary bypass,
      immediately before cardioplegic arrest. Control patients had an extra 6 minutes
      of normothermic cardiopulmonary bypass before cardioplegic arrest. Hemodynamic
      parameters were obtained before bypass, and at 1, 6, and 12 hours after weaning
      from bypass. All patients were monitored for the development of postoperative
      complications and need for inotropic agents or intraaortic balloon pumping.
      RESULTS: Preconditioned patients showed marked improvement in cardiac index from
      a preoperative value of 2.2 +/- 0.1 L x min(-1) x m(-2) to 2.5 +/- 0.1 L x min(
      1) x m(-2) at 1 hour after bypass (p < 0.01), 2.8 +/- 0.1 L x min(-1) x m(-2) at
      6 hours after bypass (p < 0.0001), and 2.9 +/- 0.1 L x min(-1) x m(-2) at 12
      hours after bypass (p < 0.0001). In the control group the cardiac index
      deteriorated significantly from 2.5 +/- 0.1 to 2.2 +/- 0.1 L x min(-1) x m(-2) at
      1 hour after bypass (p < 0.05), and then only returned to baseline at 6 and 12
      hours after bypass. Thirteen control patients required inotropic agents; however,
      none of the ischemic preconditioning group required inotropic agents (p < 0.001).
      There was no significant difference between the groups with respect to
      postoperative morbidity and mortality. CONCLUSIONS: Ischemic preconditioning
      significantly improves heart function in clinical cardiac operations, decreases
      the need for inotropic support, and could be an important adjunct to
      myoprotective strategies.

PMID- 9527207
TI  - Long-term results after repair of complete atrioventricular septal defects:
      analysis of risk factors.
AB  - BACKGROUND: We analyzed data from 320 patients to evaluate the impact of
      different preoperative, operative, and postoperative factors on the outcome after
      repair of complete atrioventricular septal defect. METHODS: Between October 1974
      and December 1995, 320 patients with complete atrioventricular septal defect not
      associated with major cardiac anomalies were operated on. Two hundred seventy
      four patients underwent total repair. Sixty-three patients (23%) were less than 6
      months old. One hundred ninety-eight (72.2%) underwent primary repair. Seventy
      six patients (27.7%) had a previous palliative operation. RESULTS: Operative
      mortality in patients who underwent primary repair decreased from 17.6% (1974 to
      1979) to 5.0% (1990 to 1995) despite an increase in the number of patients
      younger than 6 months. In patients undergoing a two-stage procedure operative
      mortality was 3.9% (late mortality, 7.9%). Young age (<6 months) was an
      incremental risk factor (p = 0.008) for operative mortality in the early study
      period. Coarctation of the aorta (p = 0.02) and severe dysplastic left
      atrioventricular valve (p = 0.001) were associated with a higher risk for
      operative mortality. Freedom from reoperation at 10 years was 82.5% +/- 3.8%.
      CONCLUSIONS: In patients with complete atrioventricular septal defect, primary
      repair is the treatment of choice and can be accomplished with good results. In
      our experience over a period of more than 20 years, earlier date of operation,
      young age (<6 months), dysplastic left atrioventricular valve, and coexisting
      coarctation were incremental risk factors for hospital death. The presence of a
      previously placed pulmonary artery band did not alter the outcome of repair. The
      reconstructed atrioventricular valve shows a good and long-lasting performance.

PMID- 9527208
TI  - Hemodynamic effects of human atrial natriuretic peptide after modified Fontan
      procedure.
AB  - BACKGROUND: Reduction of pulmonary vascular resistance and maintenance of urine
      output are important after the modified Fontan procedure. Atrial natriuretic
      peptide (ANP) has the effects of a vasodilator (including the pulmonary arteries)
      and a physiologic diuretic, and newly synthesized human ANP is available. We
      measured plasma ANP levels before and after the Fontan procedure and examined the
      effects of human ANP on hemodynamic parameters after the Fontan procedure.
      METHODS: Eight patients, aged 2 to 15 years, underwent the Fontan procedure
      (atriopulmonary connection). Blood samples were taken before and 3 hours after
      operation, and plasma ANP levels were measured by radioimmunoassay. The
      correlation between central venous pressure and ANP was examined. Human ANP was
      infused intravenously at a dosage of 0.1 microg x kg(-1) x min(-1) for 1 hour
      after the Fontan procedure under controlled ventilation and another blood sample
      was obtained. Urine volume and central venous pressure were measured, and
      pulmonary vascular resistance and the cardiac index were calculated by the
      thermodilution catheter method before and after human ANP infusion. One hour
      after human ANP infusion was discontinued, the evaluation was repeated. No other
      diuretics were given and the infusion rates of catecholamine were kept constant
      during these measurements. RESULTS: Plasma ANP levels before and after the Fontan
      procedure were 29.1 and 54.9 pg/mL, respectively, and a positive correlation was
      obtained between central venous pressure and plasma ANP levels (r = 0.661, p <
      0.05). Human ANP infusion significantly decreased central venous pressure and
      pulmonary vascular resistance, and increased urine volume and the cardiac index,
      whereas the plasma ANP level was elevated to 617.5 pg/mL. Systemic blood pressure
      did not change significantly. CONCLUSIONS: Atrial natriuretic peptide is secreted
      in response to elevated central venous pressure after the Fontan procedure, but
      its concentration might not be sufficient. Human ANP can be a therapeutic choice
      after the Fontan procedure as a physiologic diuretic and a pulmonary vasodilator.

PMID- 9527209
TI  - Minimally invasive repair of atrial septal defects.
AB  - BACKGROUND: Minimally invasive pediatric cardiac surgical techniques continue to
      evolve and remain challenged by technologic advances in percutaneous devices
      developed to treat congenital heart disease exclusive of cardiopulmonary bypass.
      Public tenacity for "incisionless" operations, however, must remain balanced
      scrupulously against the collective safety of the surgical procedure. METHODS:
      Twenty-three pediatric patients underwent repair of atrial septal defects through
      a partial sternal split and a limited skin incision (5 to 7 cm) at our
      institution between July 1995 and October 1996. RESULTS: The average age of the
      patients was 6 years and 2 months (range, 19 months to 15 years) and the average
      weight was 23.3 kg (range, 11.3 to 61.7 kg). The average bypass time was 35
      minutes (range, 19 to 81 minutes). Fourteen patients had a single dose of blood
      cardioplegia administered, whereas 9 had ventricular fibrillation electrically
      induced. Twenty-two patients had ostium secundum defects and 1 had a sinus
      venosus defect. The average length of the hospital stay was 3.6 days (range, 3 to
      6 days). There were no operative or late deaths. CONCLUSIONS: Modifications of
      this technique continue to evolve as an effective cosmetic alternative to
      submammary and thoracotomy approaches. Advantages of this modification include
      excellent cosmetic results in all age groups and the concomitant security and
      familiarity of mediastinal access and full sternotomy when required.

PMID- 9527210
TI  - Surgical management of aortopulmonary window.
AB  - BACKGROUND: Aortopulmonary window is a rare anomaly, and a variety of surgical
      techniques have been described for its closure. METHODS: We treated 6 infants
      with aortopulmonary window between 1993 and 1995. Three had associated type A
      interrupted aortic arch, and another had a muscular ventricular septal defect.
      The diagnosis was made by echocardiography, confirmed by cardiac catheterization
      in 4 infants. In 1 very sick neonate with interrupted arch, diagnosis of the
      window was considerably delayed. In 4 patients, we closed the window by using a
      flap of pulmonary artery, which was reconstructed without using a patch. In 2
      neonates with interrupted arch we anastomosed the mobilized descending aorta
      directly to the aortic defect of the aortopulmonary window, closing the pulmonary
      artery with a pericardial patch. RESULTS: There were no hospital deaths, and all
      patients are in New York Heart Association functional class I at a mean follow-up
      of 30 months. Echocardiography shows no significant distortion of the great
      vessels. CONCLUSIONS: The techniques described achieve excellent results using
      only autologous tissues with the potential for normal growth.

PMID- 9527211
TI  - Transxiphoid approach without median sternotomy for the repair of atrial septal
      defects.
AB  - BACKGROUND: Interest in minimally invasive procedures has recently increased
      because it results in less surgical trauma, decreased patient discomfort, short
      hospital stay, reduced costs, and better cosmetic appearance. Based on these
      facts, we have been using the transxiphoid process approach without sternotomy
      for the correction of atrial septal defects. METHODS: From July 1996 to January
      1997, the xiphoid process window approach was performed in 10 patients with
      ostium secundum atrial septal defect. Ages ranged from 6 months to 14 years
      (mean, 5.3 years). In all patients, extracorporeal circulation was carried out by
      means of cannulation of the femoral artery and both caval veins and of aortic
      cross-clamping. Videothoracoscopy was used to improve visualization of the aorta.
      RESULTS: There were no intraoperative or postoperative complications, and in all
      but 1 patient, extubation was possible while in the operating room. CONCLUSIONS:
      The xiphoid process window, with no median sternotomy, permitted closure of the
      atrial septal defects with good results and could be used as a less invasive
      technique for their correction.

PMID- 9527212
TI  - Implantable cardioverter-defibrillators in children: a single-institutional
      experience.
AB  - BACKGROUND: Implantable cardioverter-defibrillators have been infrequently used
      in children as therapy for resuscitated sudden death and syncope due to
      ventricular arrhythmias unresponsive to antiarrhythmics. METHODS: The medical
      records of 5 children with implantable cardioverter-defibrillators were
      retrospectively reviewed. All patients had experienced syncope and 3 (60%) an out
      of-hospital cardiac arrest. Underlying pathology included hypertrophic
      cardiomyopathy in 2, long QT syndrome in 2, and ventricular arrhythmia after
      remote repair of congenital heart disease in 1. Open thoracotomy with epicardial
      lead placement and transvenous endocardial approaches were used. RESULTS: There
      was no early or late mortality in the 5 pediatric patients undergoing implantable
      cardioverter-defibrillator placement. Postoperative complications occurred more
      frequently when open thoracotomy was used for placement. At mean follow-up of 34
      months, 4 of the 5 (80%) have received shocks. CONCLUSIONS: Implantable
      cardioverter-defibrillator is a safe and reliable therapy for children with
      resuscitated sudden death and syncope due to ventricular tachycardia unresponsive
      to antiarrhythmics. Transvenous lead placement lowers morbidity and hospital
      length of stay.

PMID- 9527213
TI  - Epithelial cell hyperproliferation after biliopancreatic reflux into the
      esophagus of rats.
AB  - BACKGROUND: Chronic reflux of duodenal contents into the esophagus of rats
      produces severe esophagitis and exerts a co-carcinogenic effect on the
      proliferating cells by enhancing the formation of nitrosamine-induced esophageal
      carcinomas. We investigated the effect of the different components of the
      duodenal reflux on the epithelial cell proliferation of the lower esophagus.
      METHODS: Sprague-Dawley rats underwent three surgical reflux models
      (biliopancreatic, pancreatic, and biliary) and a sham operation. Animals were
      sacrificed at 72 hours, 6 weeks, and 9 weeks after the operation. Histology and
      cell proliferation, determined by ornithine decarboxylase activity, polyamine
      (putrescine, spermidine, spermine) levels, and proliferating cell nuclear antigen
      labeling index of the basal and suprabasal layers, were studied in the distal
      esophagus. RESULTS: Both biliopancreatic and pancreatic reflux induced severe
      esophagitis starting on week 6. Suprabasal proliferating cell nuclear antigen
      labeling index significantly increased throughout the 9 weeks of the study in the
      biliopancreatic and pancreatic reflux groups, although this increase was earlier
      in the former group. Ornithine decarboxylase activity and polyamine levels were
      significantly increased in the biliopancreatic and pancreatic groups on week 6,
      decreasing on week 9. CONCLUSIONS: Increased esophageal cell proliferation after
      both biliopancreatic and pancreatic reflux into the lower esophagus may therefore
      be one mechanism by which duodenal-content reflux stimulates esophageal
      carcinogenesis in experimental animals.

PMID- 9527214
TI  - Esophageal carcinoma: depth of tumor invasion is predictive of regional lymph
      node status.
AB  - BACKGROUND: The depth of tumor invasion (T) and regional lymph node status (N)
      are two factors that define the stage of an esophageal carcinoma. However, the
      arrangement of staging groups assumes that these factors are independent
      variables. A retrospective review of 359 consecutive patients undergoing
      esophageal resection was conducted to define the relationship between T and N and
      to determine whether T is a significant predictor of regional lymph node
      metastasis (N1). METHODS: Primary treatment was operation without preoperative
      therapy. There were 295 (82%) adenocarcinomas, 55 (15%) squamous cell carcinomas,
      and 9 (3%) adenosquamous carcinomas. T status was Tis in 29 (8%) patients, T1 in
      65 (18%), T2 in 37 (10%), T3 in 219 (61%), and T4 in 9 (3%). N status was N0 in
      161 (45%) patients and N1 in 198 (55%). M status was M0 in 327 (91%) patients and
      M1 in 32 (9%). Stage was 0 in 29 (8%) patients, I in 58 (16%), IIA in 70 (20%),
      IIB in 22 (6%), III in 148 (41%), and IV in 32 (9%). RESULTS: The likelihood of
      N1 disease occurring with increasing T was tested using the trend test. The
      percentage of patients with N1 disease is 0% for Tis, 11% for T1, 43% for T2, 77%
      for T3, and 67% for T4 (p < 0.001). This relationship existed for both
      adenocarcinoma and squamous cell carcinoma. Multivariable analysis identified
      increasing T, adenocarcinoma, and lack of well-differentiated histologic features
      as significant predictors of N1 disease. Compared with a T1 patient, a T2 patient
      is 6 times more likely to have N1 disease, a T3 patient 23 times, and a T4
      patient 35 times. CONCLUSIONS: We conclude that for patients with esophageal
      carcinoma, T is an important predictor of N and this association should be
      included with other established factors used in clinical staging and treatment
      decisions.

PMID- 9527215
TI  - Morphologic grading of the emphysematous lung and its relation to improvement
      after lung volume reduction surgery.
AB  - BACKGROUND: The morphologic criteria for lung volume reduction surgery, such as
      severity and heterogeneity of disease, differ widely between patients, and this
      makes any comparison of functional results between centers difficult. Here we
      present a morphologic scoring system and describe its possible relation to
      functional results after lung volume reduction operations. METHODS: Between
      September 1994 and December 1996, 47 consecutive patients underwent bilateral
      lung volume reduction operations. The morphology of emphysema was quantified with
      standard chest roentgenograms and computed tomographic imaging, which were used
      to define the following four variables: degree of hyperinflation (grade 0 to 4),
      degree of impairment in diaphragmatic mechanics, degree of heterogeneity (grade 0
      to 4), and severity of parenchymal destruction (range, 0 to 48). RESULTS: All
      four variables showed good reproducibility. Degree of heterogeneity had a
      significant influence on functional improvement in terms of forced expiratory
      volume in 1 second (p = 0.0413, r2 = 0.11). Severity of parenchymal destruction
      was significantly associated with 30-day mortality: patients who died after
      operation (n = 4) had a severity of parenchymal destruction of 28.4 +/- 2.1
      compared with 21.3 +/- 1.0 for those who survived (n = 43) (p = 0.003).
      CONCLUSIONS: This morphologic scoring system is easy to use, is reproducible, and
      allows quantification of the morphology of emphysema, thereby allowing definition
      of different patient subgroups. Such an exact morphologic quantification may help
      in the comparison of functional results between centers. Furthermore, the risk
      factors for certain morphologic subgroups, such as patients with a homogeneous
      distribution pattern, may be clarified in the future.

PMID- 9527216
TI  - Experience with the two-windows method for mediastinal lymph node dissection in
      lung cancer.
AB  - BACKGROUND: Continuing to refine minimally invasive thoracoscopic surgical
      procedures, we have established the two-windows method. METHODS: Skin incisions
      required by this method consist of a 2- to 3-cm skin incision posteriorly, and a
      2- to 3-cm skin incision anteriorly in the fourth intercostal space, with the
      inferior angle of the scapula as the midpoint. We used this method to perform
      pulmonary lobectomies in combination with thoracoscopy and mediastinal lymph node
      dissection in 100 consecutive patients with lung cancer (preoperative diagnosis,
      stage I, T1 N0 M0). RESULTS: The mean operative time was 2 hours 46 minutes, the
      mean blood loss was 68.2 mL, and the mean number of mediastinal lymph nodes
      dissected was 24.3. In developing this minimally invasive thoracoscopic
      procedure, which facilitates mediastinal lymph node dissection, we realized that
      it is best performed through the fourth intercostal space. Because the tracheal
      bifurcation can be seen directly below this level, surgical manipulation in this
      area can be easily performed. This enables the same extent of mediastinal lymph
      node dissection as that performed during a standard thoracotomy. Another
      advantage of this method is that a standard posterolateral thoracotomy incision
      can be made whenever necessary by simply connecting the two incisions.
      CONCLUSIONS: We believe that the two-windows method is capable of serving as the
      standard method for the surgical treatment of stage I lung cancer.

PMID- 9527217
TI  - One-day admission for lung lobectomy: an incidental result of a clinical pathway.
AB  - BACKGROUND: Most complications after lung lobectomy are related to pain, narcotic
      analgesia, and inactivity. When the operation is performed with the goal of
      minimizing postoperative pain, and when rapid restoration of activity and patient
      independence can be achieved, most postoperative complications can be obviated
      and early discharge can be attained. METHODS: Since March 1996, we have performed
      10 consecutive elective major lung resections (8 lobectomies and 2 bilobectomies)
      for neoplastic (n = 8) and benign inflammatory (n = 2) lesions. Of the 10
      patients, 4 were men and 6 were women ranging in age from 58 to 77 years (mean
      age, 66 years). Extensive preoperative patient and family education was provided
      in the surgeon's office. Same-day admission was followed by an oblique muscle
      sparing minithoracotomy to access the chest cavity. A meticulous operation, with
      special attention to minimizing air leak and postoperative discomfort, was
      performed. Intercostal nerve cryolysis was used as the main method of analgesia.
      RESULTS: All patients underwent the planned operation through a minithoracotomy
      and were extubated in the operating room. All patients exhibited normal
      ipsilateral shoulder girdle mobility in the recovery room and none required
      intravenous narcotics after leaving this unit. All patients were out of bed the
      day of the operation. The chest tube was removed the night of the operation in 2
      patients, the morning after the operation in 6 patients, and on the second
      postoperative day in 1 patient. One patient who was discharged with a Heimlich
      valve had this device removed in the office 4 days after the operation. After the
      chest tubes were removed, there were no instances of pneumothorax. All 10
      patients were able to ambulate independently on the first postoperative day.
      Eight patients were discharged home the morning after the operation and 2 on the
      second postoperative day. None of the patients have required readmission related
      to their operation or have exhibited evidence of postthoracotomy pain syndrome.
      CONCLUSIONS: We have developed a clinical pathway based on patient education,
      meticulous minimally invasive operation, cryoanalgesia, and quick resumption of
      physical activity. Our preliminary experience with this approach has shown
      minimal morbidity, rapid restoration to preoperative status, and, for most
      patients, a 1-day hospital stay after major lung resection.

PMID- 9527218
TI  - Endoscopic treatment of bronchopleural fistulas.
AB  - BACKGROUND: Bronchial fistula is one of the most serious complications of
      pulmonary resection. METHODS: We present an endoscopic treatment that consists of
      multiple submucosal injections of polidocanol-hydroxypoliethoxidodecane
      (Aethoxysklerol Kreussler) on the margins of the fistula using an endoscopic
      needle inserted through a flexible bronchoscope. RESULTS: From 1984 to 1995, 35
      consecutive nonselected patients with a postresectional bronchopleural fistula
      were treated. All 23 partial postpneumonectomy or postlobectomy bronchopleural
      fistulas, ranging from 2 to 10 mm in diameter, healed completely. This did not
      occur in the 12 total bronchial dehiscences. No complications occurred due to the
      injection of the drug. CONCLUSIONS: In our opinion this treatment can be
      considered a valid therapeutic approach, as it is simple, safe, scarcely
      traumatic, and inexpensive, particularly considering that, in patients in stable
      condition, it can be performed as an outpatient treatment.

PMID- 9527219
TI  - Thoracoscopic splanchnicectomy for control of intractable pain in pancreatic
      cancer.
AB  - BACKGROUND: Pain is the most distressing feature of pancreatic cancer.
      Thoracoscopic splanchnicectomy, first performed in 1993, has caused a resurgence
      of interest in surgical treatment of such excruciating pain. METHODS: Twenty
      patients underwent splanchnicectomy for pancreatic cancer pain over a period of
      50 months. All were opiate dependent and unable to pursue normal daily life
      activities. We evaluated the type of splanchnicectomy performed and the long-term
      results procured. RESULTS: The number of splanchnicectomies was 24: unilateral
      videothoracoscopic splanchnicectomy, n = 11; unilateral videothoracoscopic
      splanchnicectomy with associated vagotomy, n = 5; and bilateral
      videosplanchnicectomy, n = 4. There was no postoperative complication. Pain was
      totally relieved and drug addiction stopped in 16 patients: 10 with unilateral
      videothoracoscopic splanchnicectomy, 2 with unilateral videothoracoscopic
      splanchnicectomy and associated vagotomy, and 4 with bilateral
      videosplanchnicectomy. Pain was not relieved after 4 unilateral
      videothoracoscopic splanchnicectomies, but bilateralization was not attempted in
      that subgroup. CONCLUSIONS: Unilateral videothoracoscopic splanchnicectomy is the
      treatment of choice of intractable pancreatic pain, affording drug cessation and
      recovery of daily activity in most patients. Failure may be treated secondarily
      by bilateralization with excellent results. Bilateral videosplanchnicectomy need
      not be performed by first intention.

PMID- 9527220
TI  - Terminalized semimechanical side-to-side suture technique for cervical
      esophagogastrostomy.
AB  - BACKGROUND: The classic manual end-to-side technique of esophagogastrostomy after
      gastric pull-up to the neck carries a rather high risk of fistula and stricture.
      METHODS: A terminalized semimechanical side-to-side technique of cervical
      esophagogastrostomy was performed in 16 patients by the application of an Endo
      GIA stapler across the gastric and esophageal walls placed side by side, so as to
      create a V-shaped posterior opening between the two lumina. The anterior aspect
      of the anastomosis was hand-sewn using a classic running suture. The cross
      sectional area of the semimechanical anastomoses was estimated by barium swallow
      study 2 months after operation and compared with that of 24 manual end-to-side
      esophagogastrostomies. RESULTS: The cross-sectional area was 225 +/- 15.7 mm2
      (mean +/- standard error of the mean) for the 16 semimechanical anastomoses
      versus 136 +/- 15 mm2 for the 24 manual anastomoses (p = 0.0001). The anastomotic
      area decreased from 206.6 +/- 13.5 mm2 in 29 patients without dysphagia to 107.5
      +/- 4.7 mm2 in 7 patients with moderate dysphagia for solids that did not require
      endoscopic dilation and to 55.7 +/- 16 mm2 in 4 patients with severe dysphagia
      that required dilation (p = 0). The anastomotic area in 6 of the 7 patients with
      initial moderate dysphagia for solids increased spontaneously with time from
      107.3 +/- 5.5 mm2 to 174.6 +/- 8.1 mm2, with concomitant symptomatic relief (p =
      0.0277). CONCLUSIONS: The terminalized semimechanical side-to-side suture
      technique produces a larger anastomosis than the classic end-to-side
      esophagogastrostomy technique. Inflammatory changes related to the operation may
      cause transient narrowing of a cervical esophagogastrostomy.

PMID- 9527222
TI  - Combined heart and single-lung transplantation in complex congenital heart
      disease.
AB  - We present a patient with a history of tricuspid and pulmonary atresia who
      underwent a classic Glenn shunt and a Potts shunt during childhood, resulting in
      different right and left pulmonary physiology. Because of progression of
      cardiopulmonary disease and the fact that the right lung was "protected," the
      patient underwent combined heart-left single-lung transplantation. The
      postoperative course was uneventful. Potential early and late advantages of this
      approach include simplifying of the operative procedure and mitigating the
      potential effects of obliterative bronchiolitis.

PMID- 9527221
TI  - Open-window thoracostomy and thoracomyoplasty to manage chronic pleural empyema.
AB  - BACKGROUND: The purpose of this study is to report our 15-year experience
      treating chronic empyemas after pulmonary resection and tuberculosis. METHODS:
      Open-window thoracostomy and thoracomyoplasty were used to treat 40 patients with
      chronic pleural empyema characterized by residual empyematic cavity,
      bronchopleural fistula, and persistent pleural infections that were secondary to
      tuberculosis (n = 22) or pulmonary resection (n = 18). Between 2 and 7 months
      after thoracostomy, thoracomyoplasty was performed to eliminate a persistent
      pleural cavity. In 2 patients with postpulmonary resection empyema and a large
      bronchopleural fistula, intrathoracic transposition of the latissimus dorsi flap
      and open-window thoracostomy were performed simultaneously to close the fistula.
      RESULTS: The pleural space was eliminated per primam intentionem in 21 of 22
      patients with tuberculosis and in 14 of 18 with a postpulmonary resection
      empyema. Another myoplasty was performed in an additional 3 patients to eliminate
      the pleural space. During open-window thoracostomy, the latissimus dorsi muscle
      was preserved with minimal injury to the anterior serratus muscle. One patient
      died postoperatively. CONCLUSIONS: Successful treatment of chronic pleural
      empyema requires adequate timing of surgical procedures. Our two-procedure
      technique is relatively simple and safe.

PMID- 9527223
TI  - Lung transplantation for primary pulmonary hypertension and giant pulmonary
      artery aneurysm.
AB  - We report the case of an 18-year-old patient with a giant pulmonary artery
      aneurysm and primary pulmonary hypertension who was successfully treated with
      bilateral lung transplantation and complete reconstruction of the pulmonary
      artery.

PMID- 9527224
TI  - Induced hypothermia in critical respiratory failure after lung transplantation.
AB  - Primary graft failure after lung transplantation is a serious complication with
      high mortality. We present 2 cases of critical respiratory failure after lung
      transplantation treated with surface cooling to 32 degrees and 35 degrees C,
      respectively, as an adjunct to conventional intensive care. Both patients were
      discharged from the hospital in good clinical condition. Surface cooling may be
      an effective mode of treatment in patients with critical respiratory failure
      after lung transplantation and should be considered before extracorporeal
      membrane oxygenation treatment is initiated.

PMID- 9527225
TI  - One-stage repair of interrupted aortic arch and aortopulmonary window.
AB  - Interrupted aortic arch type A with aortopulmonary window was diagnosed in a 12
      day-old neonate. A successful one-stage repair was undertaken through a midline
      sternotomy without circulatory arrest. The aortopulmonary window was closed
      through the anterior wall of communication between ascending aorta and main
      pulmonary artery with a patch. Position of the arterial cannula was changed
      during the repair, which made it possible to mobilize and expose the aortic arch
      for the completion of direct anastomosis.

PMID- 9527226
TI  - Saphenous vein graft pseudoaneurysm rupture after coronary artery bypass
      grafting.
AB  - An elderly woman underwent coronary artery bypass grafting, which was followed 1
      month later by pseudoaneurysmal rupture at the distal anastomosis of a saphenous
      vein graft. Emergency repair of the suture line dehiscence was made, and the
      postoperative course was uneventful. Pseudoaneurysm formation of a saphenous vein
      graft after coronary artery bypass grafting is a rare but potentially lethal
      complication requiring urgent operative intervention.

PMID- 9527227
TI  - Transthoracic, transdiaphragmatic excision of simultaneous lung and adrenal
      lesions.
AB  - Simultaneous adrenal and pulmonary lesions frequently present a therapeutic
      challenge to the thoracic surgeon. We describe 2 cases in which a transthoracic,
      transdiaphragmatic approach was used to establish tissue diagnosis and complete
      removal of gross tumor. In 1 case an intraoperative decision to perform a
      pneumonectomy was dictated by the tissue diagnosis of the adrenal mass, which was
      obtained with relative ease via this method. In both cases the morbidity of
      traditional approaches for adrenal operation was avoided.

PMID- 9527228
TI  - Obstructive rhabdomyoma and univentricular physiology: a rare combination.
AB  - We report the successful excision of a large left atrial rhabdomyoma producing
      complete obstruction of both inflow and outflow to the left ventricle. Systemic
      perfusion was dependent on anterograde ductual flow. The resultant univentricular
      physiology was initially managed medically, with spontaneous tumor regression
      contemplated as a means of possible long-term "cure." Failure to achieve
      hemodynamic stability compelled urgent surgical excision. This neonate was
      successfully discharged home with an in-series biventricular circulation.

PMID- 9527229
TI  - Blunt cardiac rupture caused by zip gun backfire.
AB  - A 16-year-old boy who sustained right ventricular rupture after backfiring of a
      homemade zip gun is reported. The unusual nature of this case together with the
      mechanisms and management of blunt cardiac rupture are briefly discussed.

PMID- 9527230
TI  - Right ventricular infarction during left ventricular assist system support.
AB  - Left ventricular assist devices are frequently used to bridge patients to cardiac
      transplantation. As this experience grows, new and unanticipated complications
      will occur. This report describes a 50-year-old man with ischemic cardiomyopathy
      being bridged to cardiac transplantation who suffered an acute right ventricular
      infarction during the interval of support.

PMID- 9527231
TI  - Mycotic aneurysm of the left coronary artery.
AB  - We report a 24-year-old man with mitral valve endocarditis complicated by acute
      myocardial infarction due to coronary embolism. Percutaneous transluminal
      coronary angioplasty and subsequent mitral valve replacement were performed.
      Postoperative coronary angiography revealed formation of a mycotic aneurysm of
      the left anterior descending coronary artery at the site of balloon inflation.
      The patient then underwent successful resection of the aneurysm with coronary
      artery bypass grafting.

PMID- 9527232
TI  - Minimally invasive diaphragm plication in an infant.
AB  - We report the use of video-assisted thoracic surgery to plicate the diaphragm
      after phrenic nerve injury associated with an operation for congenital heart
      disease. Right diaphragm paresis developed in a cyanotic newborn girl with
      pulmonary atresia and intact ventricular septum after a right modified Blalock
      Taussig shunt. Diaphragm plication was performed endoscopically and the patient
      recovered. Refinement of technique and instrumentation may allow wider
      application of video-assisted thoracoscopic plication of the diaphragm in
      neonatal and pediatric patients.

PMID- 9527233
TI  - Right atrial metastatic melanoma in a patient with transient ischemic attacks.
AB  - A 65-year-old-man was admitted for evaluation of a transient ischemic attack. A
      4.5 x 5.3-cm right atrial mass and a patent foramen ovale were identified by
      echocardiography. A 0.5-cm lesion was identified in the left temporal lobe of the
      brain by magnetic resonance imaging. Positron emission tomography was used to
      differentiate a tumor from an infarct in the brain. The cardiac and the brain
      lesions were successfully resected. Histopathologic study of the atrial and
      cerebral tissue demonstrated that these were metastases from a previously excised
      scalp desmoplastic malignant melanoma. The patient remains well at 14 months'
      follow-up.

PMID- 9527234
TI  - One-stage sternal stenting with homograft bone after cardiac operation in
      pediatric patients.
AB  - Low cardiac output after open heart operations in neonates and infants carries a
      high mortality. Delayed sternal closure may be life-saving but may prolong
      hospital stay and increase costs. To circumvent these issues, we shaped homograft
      bone and interposed it between the sternal edges to allow primary wound closure
      in 2 pediatric patients. Midterm results are satisfactory.

PMID- 9527235
TI  - Reversal of pulmonary arteriovenous malformation after diversion of anomalous
      hepatic drainage.
AB  - Pulmonary arteriovenous malformation can occur in up to 25% of patients after a
      classic Glenn shunt. Although unproven, exclusion of hepatic venous blood from
      the lungs has been proposed as a possible cause. We present a patient born with
      anomalous hepatic venous drainage into the left atrium with an intact atrial
      septum in whom pulmonary arteriovenous malformation developed in childhood. This
      was reversed after diversion of the hepatic venous drainage to the right atrium,
      supporting exclusion of hepatic venous flow as the cause of pulmonary
      arteriovenous malformation. The association with the hepatopulmonary syndrome is
      discussed.

PMID- 9527236
TI  - Suspension of straddling tricuspid valve chordae into the appropriate ventricle.
AB  - In 2 children with an inlet ventricular septal defect and straddling chordae
      tendineae of the septal leaflet of the tricuspid valve to the posteromedial
      papillary muscle of the mitral valve and to an accessory papillary muscle in the
      left ventricle, the straddling chordae were excised with a wedge of posteromedial
      papillary muscle and with the top segment of the accessory papillary muscle,
      respectively. After patch closure of the ventricular septal defect, the papillary
      muscle segment with its group of chordae was anchored to the right ventricular
      septum with resulting competence of the tricuspid valve. In contrast to the
      traditional repair technique, the reported modification is applicable when the
      straddling chordae insert into a papillary muscle of the mitral valve. In
      addition, various disadvantages related to the construction of a complex baffle
      in the inappropriate ventricle are avoided.

PMID- 9527237
TI  - Early repair of postinfarction ventricular septal rupture: infarct exclusion,
      septal stabilization, and left ventricular remodeling.
AB  - A surgical technique for safe early repair of ventricular septal rupture is
      described. The technique consists of exclusion of the infarcted area, septal
      stabilization, and remodeling of the left ventricle with an internal two-patch
      method. This technique is simple and reliable, and it appeared favorable in an
      elderly patient group. Six of 7 patients were treated with good results.

PMID- 9527238
TI  - Thoracoscopic limited pericardial resection with an ultrasonic scalpel.
AB  - We employed an ultrasonic scalpel, the Harmonic Scalpel (Ethicon Endo-Surgery,
      Cincinnati, OH), for thoracoscopic limited pericardial resection in consecutive
      10 patients with massive pericardial effusion or pericarditis. The mean operative
      time was 27 minutes for pericardial effusion. No dangerous arrhythmias were
      induced even in the patient with dense pericardial adhesions. There were no
      operation-related complications or deaths. The thoracoscopic ultrasonic scalpel
      technique can be an efficacious minimally invasive alternative for pericardial
      window.

PMID- 9527239
TI  - Endomyocardial biopsy in the heterotopic heart transplant patient.
AB  - We present a technique for rapid and easy endomyocardial biopsy of the
      heterotopic transplanted heart. With a recent resurgence in heterotopic heart
      transplantation, we believe that ours is a sound technique in obtaining both
      routine surveillance biopsies as well as evaluating "right-sided pressures" in
      the "piggy-back" heart.

PMID- 9527240
TI  - Semicontinuous suture technique for all prosthetic valve insertions: the "hoist"
      technique.
AB  - The semicontinuous suture technique as an alternative method in valve replacement
      is described. This specific technique is applicable for both adults and children
      requiring valvular prosthetic operations. This method combines advantages of the
      continuous and interrupted suture techniques.

PMID- 9527241
TI  - Method for creation of the aortotomy site for saphenous vein grafts.
AB  - Saphenous vein coronary artery bypass grafting requires a proximal anastomosis of
      the vein to the aorta. A variety of techniques have been described to create the
      aortotomy. We have developed a four-sided knife (Xcision Scalpel; patent pending,
      Research Medical, Inc, Midvale, UT) that facilitates the creation of a more
      uniform circular aortotomy. The purpose of this communication is to describe the
      knife and the technique for its use.

PMID- 9527243
TI  - Esophageal perforation.

PMID- 9527242
TI  - The biology of estrogen-mediated repair of cardiovascular injury.
AB  - Women appear to be protected from cardiovascular disease until the onset of
      menopause. Considerable evidence supports the atheroprotective effects of
      endogenous and supplemental estrogens. The beneficial effects of estrogens on
      lipid metabolism cannot wholly explain this phenomenon. Accumulating data suggest
      that estrogen may act at the cellular and molecular level to influence
      atherogenesis. The purpose of this review is to examine lipid-independent
      mechanisms of estrogen-mediated atheroprotection after cardiovascular injury.

PMID- 9527244
TI  - As originally published in 1990: Prolonged extracorporeal life support of
      pediatric and adolescent cardiac transplant patients. Updated in 1998.

PMID- 9527245
TI  - 1995 coronary artery bypass risk model: The Society of Thoracic Surgeons Adult
      Cardiac National Database.
AB  - BACKGROUND: The Society of Thoracic Surgeons (STS) Adult Cardiac National
      Database has recently completed the development of the 1995 risk model to be used
      to estimate the risk of operative death for isolated coronary artery bypass graft
      (CABG) procedures. This article describes the detailed methodology used, as well
      as a new Expert Advisory Panel review mechanism that was initiated by The
      Society. METHODS: Placing emphasis on clinical relevance, data quality, data
      completeness, and univariate analyses, a logistic regression analysis was used to
      develop the 1995 CABG-only risk model. The STS National Office invited an Expert
      Advisory Panel (composed of nationally recognized, independent biostatisticians)
      to review the modeling process used. RESULTS: The 1995 CABG-only model details
      are reported. Standard performance measures indicated the model had high
      predictive power and an acceptable level of calibration. The Expert Advisory
      Panel reviewed the 1995 CABG model and concluded that the current modeling
      techniques were adequate. Suggestions for future model development and reporting
      were proposed by the Panel. CONCLUSIONS: The most current STS risk model of CABG
      operative mortality is a reliable and statistically valid tool. Its development
      and performance have been critically examined and approved by an independent
      panel of experts.

PMID- 9527246
TI  - Refined alpha aminooleic acid and experimental calcification in bioprostheses.

PMID- 9527247
TI  - Transapical aortic cannulation in pediatric patients.

PMID- 9527248
TI  - Pulmonary valve replacement: a role for mechanical prostheses?

PMID- 9527249
TI  - Modified T grafts: the Tarzan factor.

PMID- 9527250
TI  - Rapid cooling contracture with cold cardioplegia.

PMID- 9527251
TI  - Laceration of the external iliac artery with a pediatric intraaortic balloon
      catheter.

PMID- 9527252
TI  - Cervical mediastinoscopy as an adjunct to facilitate mediastinal lymph node
      dissection.

PMID- 9527253
TI  - Time to learn echocardiography.

PMID- 9527254
TI  - Internal mammary artery branch steal in myocardial revascularization.

PMID- 9527256
TI  - Biventricular repair of hypoplastic left heart disease: a realistic goal?

PMID- 9527255
TI  - Is semiskeletonization of internal thoracic artery another new harvest technique?

PMID- 9527257
TI  - Haemo-glyde coated chest drainage tubes.

PMID- 9527258
TI  - Reimplantation of infected antiarrhythmic implantable devices.

PMID- 9527259
TI  - Trimodality therapy for esophageal cancer.

PMID- 9527260
TI  - Note to the editor.

PMID- 9527261
TI  - Risk of recurrence after treatment of early breast cancer with skin-sparing
      mastectomy: two editorial perspectives.

PMID- 9527262
TI  - Preoperative idoxuridine and radiation for large soft tissue sarcomas: clinical
      results with five-year follow-up.
AB  - BACKGROUND: Local control remains an important issue in the management of large
      soft tissue sarcomas. Radiation is the main adjuvant to surgery for local therapy
      of sarcomas, but it requires relatively high doses, hitherto considered
      prohibitive in areas such as the retroperitoneum. We developed a preoperative
      treatment approach to large soft tissue sarcomas that would deliver a high total
      dose of radiation administered in conjunction with the halogenated pyrimidine
      radiosensitizer idoxuridine (IdUrd). METHODS: Thirty-seven patients with large
      sarcomas of the head and neck, mediastinum, retroperitoneum, or extremity
      received three or five cycles of sequential IdUrd infusion (1000-1600 mg/m2/d x 5
      d) alternating weekly with twice daily radiation (125-150 cGy per dose) and were
      then evaluated for resection. The delivered preoperative radiation dose was up to
      6250 to 7500 cGy. RESULTS: Five patients (14%) had a partial response to
      preoperative therapy, and 28 of 37 patients underwent successful resection. There
      were no intra- or postoperative deaths. Local control was achieved in 19 of 28
      resected patients, but in only 1 of 6 patients who remained unresectable despite
      therapy. With a median follow-up of 5.8 years, 28% of patients are alive with no
      evidence of disease, 17% are alive with disease, and 53% have died of their
      disease. CONCLUSIONS: Using the dose and schedule we employed, resection of large
      soft tissue sarcomas was possible after high-dose radiation delivered in
      conjunction with IdUrd. Although local control was acceptable, the high rate of
      distant failure represents a limitation of any local approach to the treatment of
      large soft tissue sarcomas and suggests the need for integration of this approach
      with an effective systemic therapy.

PMID- 9527263
TI  - Radiation and chemotherapy instead of surgery for low infiltrative rectal
      adenocarcinoma: a prospective trial.
AB  - BACKGROUND: The objective of this prospective study was to determine the
      possibility of treatment based exclusively on chemotherapy and radiotherapy for
      patients with low infiltrative rectal tumors in an attempt to preserve sphincter
      function. METHODS: Sixteen patients with rectal adenocarcinoma up to 3 cm above
      the pectineal line with initial indications for abdominoperineal resection (APR)
      were submitted to a 5040-cGy (28 x 180 cGy) radiotherapy dose and chemotherapy
      during the first 3 and last 3 days of radiotherapy, using 425 mg/m2/day of 5
      fluorouracil (5FU) and 20 mg/m2/day of folinic acid. Levamisole was used at 150
      mg/day for 3 consecutive days at 2-week intervals throughout the period of
      therapy. Patients with a complete response were not submitted to APR, but
      received additional brachytherapy for curative purposes with doses from 2000 to
      3000 cGy. Patients with recurrence after a complete response, with partial
      response, or with no response were submitted to APR. RESULTS: Six patients
      (37.5%) presented a complete response, five (31.25%) presented a partial
      response, and five (31.35%) did not respond. The disease-free interval ranged
      from 1 to 34 months (mean = 11 months) among the six patients with complete
      response, and only one patient not submitted to APR is currently asymptomatic.
      Among the 15 patients with an indication for APR, three refused surgery because
      of full improvement of clinical symptoms and currently have tumor activity in the
      rectum. Mean patient follow-up was 23.8 months (8 to 43 months), and ten patients
      (62.5%) showed no evidence of active disease at last follow-up. CONCLUSIONS: The
      therapeutic schedule used was not effective in preserving sphincter function in
      patients with low infiltrative rectal adenocarcinoma, because responses, although
      very frequent, were only temporary.

PMID- 9527264
TI  - Results of complete lymph node dissection in 83 melanoma patients with positive
      sentinel nodes.
AB  - BACKGROUND: The technique of sentinel lymph node (SLN) biopsy for melanoma
      provides accurate staging information because the histology of the SLN reflects
      the histology of the entire basin, particularly when the SLN is negative.
      METHODS: We combined two mapping techniques, one using vital blue dye and the
      other using radiolymphoscintigraphy with a hand-held gamma Neoprobe, to identify
      the SLN in 600 consecutive patients with stage I-II melanoma. The SLNs were
      examined using conventional histopathology and immunohistochemistry for S-100.
      RESULTS: Eighty-three (13.9%) patients had micrometastatic disease in the SLNs.
      Thirty percent of patients with primary melanomas greater than 4.0 mm in
      thickness had positive SLNs, followed by 48 of 267 (18%) of patients with tumors
      between 1.5 mm and 4 mm, and 12 of 169 (7%) of those with lesions between 1.0 mm
      and 1.5 mm. No patient with a tumor less than 0.76 mm in thickness had a positive
      SLN. Sixty-four of the 83 SLN-positive patients consented to undergo complete
      lymph node dissection (CLND), and five of 64 (7.8%) of the CLNDs were positive.
      All patients with positive CLNDs had tumor thicknesses greater than 3.0 mm.
      CONCLUSIONS: The rate of SLN-positive patients increases with increasing
      thickness of the melanoma. SLN-positive patients with primary lesions less than
      1.5 mm in thickness may have disease confined to the SLN, thus rendering higher
      level nodes free of disease, and may not require a CLND.

PMID- 9527265
TI  - Sentinel node biopsy in breast cancer.
AB  - BACKGROUND: Sentinel lymph node biopsy (SNB) in breast cancer may be used in
      place of axillary lymph node dissection (ALND) if SNB accurately stages the
      axilla. This study assessed the success and accuracy of axillary SNB with
      isosulfan blue (ISB) and technetium-99 sulfur colloid (TSC) compared to ALND.
      METHODS: Forty-two women with T1 or T2 breast cancer underwent SNB and ALND.
      Sixty to 90 minutes before anesthetic induction, a mixture of 3 mL ISB and 1 mCi
      TSC was injected around the primary cancer or prior biopsy site.
      Intraoperatively, the SLN was identified using a gamma detector (Neoprobe 1000)
      or by visualization of the blue-stained lymph node and afferent lymphatics. The
      SLN was excised separately, and a level I/II ALND was completed. The histologic
      findings of the axillary contents and SLN were compared. RESULTS: An axillary SLN
      was found in 38 of 42 (90%) cases. SLN localization rate and predictive value
      were the same for women who had and those who had not undergone excisional biopsy
      before the date of SNB. Fifteen of 42 (36%) patients had lymph node metastases.
      The SLN was positive in all women with axillary metastases (negative predictive
      value, 100%). CONCLUSIONS: If confirmed by larger series, a negative SNB may
      eliminate the need for ALND for select women with breast cancer.

PMID- 9527266
TI  - Axillary lymph node dissection for breast cancer: a decision analysis of T1
      lesions.
AB  - BACKGROUND: The value of routine axillary dissection for patients with breast
      cancer is still being debated. The argument centers around whether the
      information gained by knowing the lymph node status, which aids in making the
      decision about adjuvant chemotherapy, justifies the morbidity. This study
      quantitatively analyzes the potential outcomes of routine, selective, and no
      axillary dissection. METHODS: A decision analysis was performed of the strategies
      of lumpectomy and radiation versus simple mastectomy followed by no dissection,
      selective dissection, or routine dissection. Factors included biologic markers to
      identify high-risk lesions, the morbidity of axillary dissection, the effects of
      adjuvant chemotherapy on lymph node-negative and lymph node-positive disease, and
      the life expectancy of patients with high-risk and low-risk node-negative and
      node-positive lesions. Sensitivity analysis was done to determine threshold
      levels of these factors in choosing an option. RESULTS: We discovered an
      advantage in quality-adjusted life expectancy (QALE) for no axillary dissection
      until the probability of positive lymph nodes reaches >15%; after that, selective
      node dissection is superior. Selective dissection is superior for lower morbidity
      rates of axillary dissection. Routine dissection is never a superior strategy.
      The difference among these strategies is small, however, with no one strategy
      providing a QALE greater than 1 year longer than any other. CONCLUSIONS: Axillary
      dissection can be avoided in patients with high-risk lesions who would be
      candidates for adjuvant chemotherapy regardless of lymph node status, and
      possibly in patients with low-risk T1a lesions, but it should be recommended for
      low-risk T1b and T1c lesions for which lymph node status may determine the need
      for adjuvant chemotherapy.

PMID- 9527267
TI  - Association between extent of axillary lymph node dissection and survival in
      patients with stage I breast cancer.
AB  - BACKGROUND: The role of axillary lymph node dissection for stage I (T1N0) breast
      cancer remains controversial because patients can receive adjuvant chemotherapy
      regardless of their nodal status and because its therapeutic benefit is in
      question. The purpose of this study was to determine whether extent of axillary
      dissection in patients with T1N0 disease is associated with survival. METHODS:
      Data from 464 patients with T1N0 breast cancer who underwent axillary dissection
      from 1973 to 1994 were examined retrospectively. Kaplan-Meier estimates of
      overall survival, disease-free survival, and recurrence were calculated for
      patients according to the number of lymph nodes removed (<10 or > or = 10; <15 or
      > or = 15), and survival curves compared using the Wilcoxon-Gehan statistic. Cox
      proportional hazards regression modelling was used to adjust for confounding
      prognostic variables. RESULTS: Median follow-up time was 6.4 years. Patient
      groups were similar in age, menopausal status, tumor size, hormonal receptor
      status, type of surgery, and adjuvant therapy. There was a statistically
      significant improvement in disease-free survival in the > or = 10 versus <10
      nodal groups (P <.01). Five-year estimates of survival were 75.7% and 86.2% for
      <10 nodes and > or = 10 nodes, respectively; 10-year estimates were 66.1% and
      74.3%. There also was a notable improvement in the survival comparison of
      patients with <15 versus > or = 15 nodes (P < or = .05). These findings were
      confirmed in the multivariate analysis. CONCLUSIONS: These results may reflect a
      potential for misclassification of tumor stage among patients who had fewer nodes
      removed. The data, however, suggest that in patients with Stage I breast cancer,
      improved survival is associated with a more complete axillary lymph node
      dissection.

PMID- 9527268
TI  - Selection of local therapy after neoadjuvant chemotherapy in patients with stage
      IIIA,B breast cancer.
AB  - BACKGROUND: Stage IIIA,B breast cancer is commonly treated with neoadjuvant
      chemotherapy because of high objective response rates and improved operability.
      Criteria for subsequent selection of local therapy--mastectomy, radiotherapy, or
      both--are not well defined. We adopted a policy of selective local therapy based
      on rebiopsy of the breast and clinical axillary lymph node status at the time of
      best response to chemotherapy. METHODS: Between 1980 and 1993, 126 patients with
      stage IIIA,B breast cancer were treated with neoadjuvant chemotherapy and
      definitive local therapy. The long-term incidence of locoregional failure (in
      breast, chest wall, axilla, supraclavicular, neck), relapse-free survival, and
      overall survival was determined. RESULTS: The overall clinical objective response
      rate to chemotherapy was 95.2%. Eighty-three patients underwent mastectomy, with
      negative margins achieved in 91.6%. Forty-two patients had breast preservation;
      the overall in-breast recurrence rate was 19.0% (8 of 42 patients). The overall
      locoregional recurrence rate by site was: chest wall-8.7% (11 of 126 patients),
      axilla-8.7% (11 of 126 patients), supraclavicular-5.6% (7 of 126 patients), and
      neck-4.0% (5 of 126 patients). The axillary recurrence rate was 6.6% (5 of 76
      patients) for clinically negative axilla treated with radiotherapy only, and
      12.0% (6 of 50 patients) for clinically positive axilla treated with surgery
      only. The overall long-term survival probabilities (6 years) according to stage
      were: stage IIIA-58.0%, stage IIIB(noninflam)-58.0%, stage IIIB(inflam)-36.0%.
      CONCLUSIONS: These findings support a selective approach to local therapy in
      patients with stage IIIA,B breast cancer. This approach provides local control in
      most patients, and allows for breast preservation and elimination of axillary
      dissection in selected patients.

PMID- 9527269
TI  - Management, morbidity, and oncologic aspects in 100 consecutive patients with
      immediate breast reconstruction.
AB  - BACKGROUND: Immediate breast reconstruction (IBR) is indicated when breast
      conserving surgery is inappropriate and the patient refuses mastectomy as the
      sole procedure. METHODS: Management, morbidity, and oncologic aspects were
      studied in 100 consecutive patients treated between 1990 and 1994 with a minimum
      follow-up time of 2 years. Indications for mastectomy and IBR always were
      discussed within a multidisciplinary group. Eighty-four patients had primary
      breast cancer, 12 patients underwent salvage mastectomy for an ipsilateral breast
      tumor recurrence, two patients had benign breast disease, and two patients
      underwent prophylactic mastectomy because of familial breast cancer. RESULTS:
      Saline and silicone gel-filled implants were used predominantly (88%), but free
      and pedicled TRAM flaps were performed in 12 patients (12%). The overall
      complication rate was 16%. Seven patients lost their implants, three of whom had
      been irradiated to the chest wall. Sixty-five patients completed breast
      reconstruction (nipple and areola) within a median time of 418 days (range 40 to
      1471 days). At follow-up, eight patients had locoregional recurrences after a
      median time of 7.2 months (range 1 to 23 months), and nine patients had died from
      disseminated breast cancer. CONCLUSION: IBR is time-consuming, but it is well
      tolerated and does not interfere with oncologic adjuvant treatment. IBR can be
      performed with low morbidity by a dedicated multidisciplinary team.

PMID- 9527270
TI  - Comprehensive needs assessment of clinical breast evaluation skills of primary
      care residents.
AB  - BACKGROUND: Health care reform places primary care (PC) physicians in an
      increasingly significant role for breast cancer screening and diagnosis. This
      study assessed the adequacy of traditional PC resident training to prepare
      physicians for this front-line role. METHODS: Sixty-eight primary care residents,
      representing seven training programs, participated in a multidimensional needs
      assessment study of clinical breast evaluation skills. RESULTS: Performance
      deficiencies noted in each component were most significant in (1) common breast
      problem management (problem-solving mean 44.51 +/- 11.01); (2) breast examination
      skills (mean 49.65 +/- 14.48%); and (3) lump detection sensitivity (mean 40.20 +/
      17.10%). Overall examination reliability was good (alpha = .82). Factorial ANOVA
      revealed significant performance differences among training programs. Residency
      programs with higher performance levels reported dedicated breast curricula, and
      residents rated these programs as providing more adequate training. Programs with
      poorer performance in breast examination lacked curriculum emphasis, with
      residents describing training received as poor to fair. CONCLUSION: This study
      demonstrated performance deficits in the clinical breast evaluation skills of
      graduating PC residents that have not been captured by traditional evaluation
      methodologies. This may represent a limitation in the ability of many PC
      physicians to effectively screen and diagnose patients with breast cancer.

PMID- 9527271
TI  - Results of laparoscopic pelvic lymphadenectomy in patients at high risk for nodal
      metastases from prostate cancer.
AB  - BACKGROUND: Laparoscopic pelvic lymphadenectomy (LPLND) can be performed safely
      and with minimal morbidity in the staging of prostate cancer. Its utility in
      evaluating patients at high risk for metastatic disease before primarily
      nonsurgical treatment modalities was evaluated. METHODS: Twenty-four consecutive
      patients who underwent LPLND between June 1993 and July 1996 were studied. These
      patients were considered poor surgical candidates based on several risk factors,
      as follows: elevation of serum PSA >20 in 19 patients (79%); elevation of serum
      acid phosphatase in 4 patients (17%); digital rectal examination findings
      indicative of extraprostatic extension or seminal vesical involvement in 14
      patients (58%); and poorly differentiated tumors on prostate biopsy in 19
      patients (79%). Nineteen patients (79%) had two or more of these risk factors.
      Median PSA for the entire series of patients was 35.2 ng/mL (range 7.9 to 133
      ng/mL), and median Gleason score was 7 (range 5 to 9). Preoperative CT or MRI was
      negative for pelvic lymph node metastases in 17 of 23 patients (79%), and bone
      scan was negative in all 24 patients. RESULTS: Unilateral (n = 2) or bilateral (n
      = 22) LPLND was performed in all patients. Six patients (25%) had lymph node
      metastases detected laparoscopically. Five of the six patients had palpable
      extraprostatic extension (T3a/b) or invasion of a seminal vesical (T3c), and in
      four of these patients the site of the metastatic lymph nodes was ipsilateral to
      the palpable prostate abnormality. None of the risk factors was independently
      predictive of lymph node metastases within this series of patients. An average of
      10.8 +/- 6.5 lymph nodes was removed at a mean operative time of 174 +/- 10
      minutes for patients undergoing bilateral LPLND. Estimated blood loss was minimal
      for 20 of 22 patients (92%) undergoing LPLND alone, and there were no
      complications requiring open exploration. Mean postoperative hospital stay was
      1.2 +/- 0.5 days for patients undergoing LPLND alone. CONCLUSIONS: LPLND can be
      used efficiently to identify patients with nodal metastases from select high-risk
      patients. This, in turn, can exclude such patients from noncurative local and
      regional therapy.

PMID- 9527272
TI  - Absence of frequent involvement of modifier of Min(APC) in sporadic colorectal
      cancer.
AB  - BACKGROUND: Mutations in the multiple intestinal neoplasia (Min) gene, the mouse
      homologue of the APC gene, result in the development of intestinal tumors. The
      degree of tumor expression is suppressed by the modifier of Min (MOM).
      Alterations in the MOM gene result in markedly increased tumor expression in the
      mouse. The human homologue of the MOM gene has been mapped to a locus on
      chromosome 1p35-36, but the role of the MOM gene in the development of human
      sporadic colorectal cancers has not been defined. METHODS: The microsatellite
      marker D1S199 has been previously mapped to the region of the MOM gene and was
      used as a primer for PCR amplification. The PCR products were subjected to
      denaturing electrophoresis and analyzed for loss of heterozygosity (LOH) and the
      mismatch repair phenomenon (RER) of each tumor compared to its mucosal control.
      RESULTS: 48 consecutive sporadic colorectal cancers and normal adjacent mucosa
      were analyzed. LOH was noted in 2 of 48 tumors and the RER phenomenon was noted
      in 6 of 48 tumors. Thus, 8 of 48 tumors (16.7%) showed alterations in the region
      of the locus of the MOM gene. There was no association between alterations in
      this region and TNM stage, disease-free survival, overall survival, or p53
      mutation. CONCLUSIONS: Although mutation of the APC gene is an integral component
      of sporadic colorectal carcinogenesis, alteration in the region including the MOM
      gene does not appear to play a significant role in the development or
      clinicopathologic behavior of human sporadic colorectal tumors.

PMID- 9527273
TI  - Detection of telomerase activity in breast masses by fine-needle aspiration.
AB  - BACKGROUND: Telomerase is an RNA-dependent DNA polymerase that compensates for
      the telomere shortening that occurs in its absence. Reactivation of telomerase is
      thought to be an important step in cellular immortalization, and recent studies
      have indicated that telomerase activity is often detected in primary human
      malignancies. The clinical implications of telomerase activity in human tumors
      are currently under investigation. METHODS: Eighty-nine samples (46 FNAs and 43
      gross tissue biopsies) from 44 patients with breast masses were analyzed
      prospectively for the presence of telomerase activity by a modification of the
      telomere repeat amplification protocol (TRAP). All samples were obtained directly
      from the excised mass at the time of specimen removal in the operating room.
      RESULTS: Telomerase activity was detected in 17 of 19 (90%) FNA samples and 15 of
      18 (83%) invasive breast cancer tissue biopsies. Telomerase was also detected in
      9 of 16 (56%) FNAs and 8 of 15 (53%) tissue biopsies from 16 fibroadenomas. Other
      benign proliferative lesions (n = 5) did not have detectable telomerase activity
      in either FNA or tissue specimens. FNA-TRAP results correlated with the gross
      tissue specimen TRAP results in 95% of all cases. CONCLUSION: The FNA-TRAP assay
      for telomerase detection is a highly sensitive and accurate method for the
      detection of telomerase activity in breast masses. Future application of these
      techniques should facilitate evaluation of telomerase as a tumor marker in the
      clinical management of breast and other solid malignancies.

PMID- 9527274
TI  - Altered serum levels of insulin-like growth-factor binding proteins in breast
      cancer patients.
AB  - BACKGROUND: Insulin-like growth factor 1 (IGF-1) has mitogenic properties for
      breast cancer cell lines and has been proposed to be an important factor in
      breast carcinogenesis. We hypothesized that differences in IGF-1 or its binding
      proteins might increase susceptibility to breast cancer. This case-control study
      was designed to investigate whether patients with breast cancer have altered
      levels of either IGF-1 or its intermediary modulatory proteins, the IGF binding
      proteins (BP). METHODS: Serum was collected from 90 patients (63 with breast
      cancer and 27 with benign breast disease) after an overnight fast and before
      surgery. IGF-1, BP1, and BP3 levels were determined by immunoradiometric assays.
      In a subset of 66 patients, Western ligand blots were also performed for a
      semiquantitative measurement of functioning BP levels. A forward stepwise
      logistic regression model to adjust for other confounding variables (age,
      menopausal status, parity, age at menarche, use of oral contraceptives, history
      of breast biopsy, family history of breast cancer, hormone replacement therapy,
      and body-mass index) was used in the multivariate analysis. RESULTS: Serum IGF-1
      levels were similar in cases and controls. However, levels of BP3 (p < 0.001),
      BP4 (p < 0.01), and BP1 (p < 0.05) were significantly associated with risk of
      breast cancer. The level of BP3 was the most significant factor predictive of
      breast cancer. The odds ratio for breast cancer in women with BP3 levels >2066
      ng/ml was 0.18 (95% CI, 0.05-0.55). Correspondingly, women with BP1 levels higher
      than 39 ng/ml had an odds ratio of 0.21 (95% CI, 0.07-0.68) for breast cancer.
      When considering only cancer patients (n = 63), decreasing levels of BP4 (p <
      0.01) and increasing levels of BP1 (p < 0.02) were significantly associated with
      progesterone receptor positivity (PR+) in the tumor. The odds ratio of PR+ in
      patients with BP1 levels higher than 34 ng/ml was 7.49 (95% CI, 1.5-37.4). Better
      grade of tumor (well and moderately differentiated) was observed in patients with
      higher levels of BP3 (p < 0.03). CONCLUSIONS: Distinct differences in BP profiles
      exist among patients with breast cancer and also among those with high-grade,
      hormonal receptor-negative tumors. These findings suggest that the
      bioavailability of IGF-1 as mediated by its binding proteins may participate in
      both breast carcinogenesis and selection of more aggressive breast carcinomas.

PMID- 9527275
TI  - The influence of recombinant human erythropoietin on tumor necrosis factor alpha
      and interleukin-10 production by whole blood cell cultures in hemodialysis
      patients.
AB  - Impaired immunological response in hemodialysis (HD) patients, which leads to
      inappropriate cytokine production, is partially caused by the hyperstimulation of
      both T lymphocytes and monocytes/macrophages. Recent data suggest that human
      recombinant erythropoietin (rhEPO) may have an immunological action. The goal of
      our study was to estimate the influence of rhEPO treatment on the production of
      the inflammatory cytokine tumor necrosis factor alpha (TNFalpha) and
      antiinflammatory cytokin interleukin-10 (IL-10) in 10 HD patients receiving rhEPO
      for 6 months. The levels of cytokines were measured in the in vitro cultures of
      whole blood. The level of IL-10 increased in all treated patients during the
      therapy, and it was accompanied by a transitory decrease of TNFalpha. The results
      of our studies suggest that rhEPO may reduce the inflammatory process by
      decreasing production of TNFalpha and increasing production of IL-10.

PMID- 9527276
TI  - The management of end-stage renal disease in India.

PMID- 9527277
TI  - Treatment of end-stage renal disease in central and eastern Europe: overview of
      current status and future needs.
AB  - The situation of end-stage renal disease (ESRD) patients in central and eastern
      Europe was very poor for many years during the so called socialistic era.
      Economical and political liberation resulted in the significant growth of renal
      replacement facilities in this region. The number of hemodialysis units increased
      significantly (56%) during the period 1990-1996, and the number of patients
      treated with this modality has risen by 75%. More dramatic progress was achieved
      in peritoneal dialysis. The number of units performing this method of renal
      replacement therapy (RRT) increased by 277% and the number of patients by more
      than 300%. Not only quantitative but also qualitative changes were observed. More
      modern hemodialysis machines installed in the vast majority of units allow for
      the performance of bicarbonate dialysis, controlled ultrafiltration, and sodium
      profile modeling. Also, a wider choice of biocompatible dialyzers has become
      available during the last few years. The number of centers performing renal
      transplantation has increased significantly, but the number of renal transplants
      has not followed this progress. Despite all the progress, further development of
      all RRT methods is necessary to achieve acceptance rates comparable to those
      observed in developed countries.

PMID- 9527278
TI  - The acute effect of intravenously administered recombinant human erythropoietin
      on the immune response of uremic patients maintained on regular hemodialysis.
AB  - The uremic patient on regular hemodialysis (RHD) is subjected to a wide range of
      immune modulators including the uremic state per se, multiple transfusions and
      exposure to bioincompatible materials and endotoxins. Erythropoietin (EPO)
      therapy may raise concern about its potential influence on this complex scenario.
      To envisage this issue, 15 adequately selected patients, stable on RHD, were
      randomly assigned in a 2:1 ratio into EPO and placebo groups. After initial
      assessment and determination of baseline values, they received, in a double-blind
      manner, either EPO or normal saline as an intravenous bolus immediately after
      termination of dialysis for 30 successive sessions. Thirty minutes later,
      following sessions 1, 10, 20, and 30, samples were obtained for determination of
      blood counts, red cell indices, peripheral lymphocyte counts (PLC), CD4/CD8
      ratios, blood EPO levels, and serum concentrations of interleukins (IL) IL-2r, IL
      3, and IL-6, tumor necrosis factor (TNFs and TNFalpha), and neopterin (NPT).
      Blood EPO levels displayed the predicted rise in the EPO group, which correlated
      with partial improvement of red cell parameters. The mean total leukocyte count
      and PLCs was significantly increased in the EPO group (p < 0.05) but not in the
      placebo group. CD4/CD8 ratios were not significantly changed in either group. The
      serum concentrations of IL-2r, IL-3, and NPT remained fairly stable while that of
      IL-6 was widely variable in both study groups. The mean serum concentrations of
      TNF and particularly TNFalpha showed a steady and statistically significant
      increment in the EPO group from 6 to 41 pg/ml (p < 0.05) and 93 to 128 pg/ml (p <
      0.03), respectively. No significant change was noticed in the control group. It
      is concluded that intravenous administration of EPO under the conditions of this
      study may have an immune stimulating effect. This is shown by the release of
      TNFs, which in turn may be responsible, through different potential mechanisms,
      for the increase in the mean peripheral neutrophil count and the blunting of
      erythroid responsiveness to EPO therapy.

PMID- 9527279
TI  - Plasmapheresis in the treatment of posttransplant cardiomyopathy.
AB  - After heart transplantation a number of factors such as pre- and postoperative
      hypoxia of the myocardium, myocardial failure of the early postoperative period,
      acute rejection episodes, cytomegalovirus infection, and finally the progressive
      atherosclerosis of the coronary arteries lead to the development of transplanted
      heart failure. Severe alterations of the myocardial function at this end stage of
      the process correspond to incurable cardiomyopathy. The target of plasmapheresis
      in this case is to decrease the extent of the disturbances in the lipoprotein
      contents and blood rheology for the improvement of the coronary perfusion of the
      transplanted heart. Nine patients with 3-7 year survival periods after heart
      transplantations underwent plasmapheresis twice a year using the Haemonetics PCS
      plus machine. 2,100-2,700 ml of plasma was removed. Biochemical data, rheology
      and coagulation, and the concentration of Sandimmune (Sandoz Pharma Ltd., Basel,
      Switzerland) were controlled, and radionuclide scintigraphy of the myocardium,
      coronarographia, and transesophageal ultrasound investigations were completed for
      these patients. The result was the significant improvement of the coronary
      perfusion of the myocardium. The level of immunosuppression after the
      plasmapheresis procedures did not change and therefore did not demand any
      correction. Thus, we think that plasmapheresis can be an effective method of
      treatment of posttransplantation cardiomyopathy; the improvement of coronary
      perfusion decreases the extent of chronic ischemia. Further studies are necessary
      to answer the question as to whether it is possible to prolong the time before
      retransplantation with the help of plasmapheresis.

PMID- 9527281
TI  - The chemical protecting group concept applied in crosslinking of natural tissues
      with glutaraldehyde acetals.
AB  - This work describes the results of the controlled crosslinking of collagen
      matrices by glutaraldehyde based on a double protection strategy, glutaraldehyde
      acetals and lysine protonation due to the acidic conditions of acetal formation.
      Materials crosslinked by this approach were characterized by thermal stability
      comparable to those obtained by conventional procedures with mechanical
      properties expected for bioprosthesis manufacture and with a higher stability
      toward collagenase hydrolysis. The integrity of the microfibrillar structure was
      confirmed by optical and scanning electronic microscopy. The results indicate
      that the glutaraldehyde acetals procedure may be of potential use for the
      crosslinking of bovine pericardium used in the manufacture of bioprosthetic
      devices. Advantages may be related to the production of materials with
      homogeneous crosslinking distributions, associated with better definition in the
      nature of the chemical link that they introduce, due to a better distribution of
      glutaraldehyde within the tissue matrix before the crosslinking reaction is
      allowed to occur. As a result, materials with improved biological and mechanical
      properties are expected.

PMID- 9527280
TI  - Anionic collagen: polymer composites with improved dielectric and rheological
      properties.
AB  - This work describes the preparation and characterization of anionic collagen
      composites with rhamsan and vinylidene fluoride-trifluorethylene with improved
      rheological and dielectric properties without loss of collagen secondary
      structure with an interaction occurring between both macromolecules of the
      composites. On a comparative basis, the force needed for the extrusion of anionic
      collagen:rhamsan composites was in the range from 0.088 to 0.080 J compared to
      that for collagen of 0.189 J. Anionic collagen:vinylidene fluoride
      trifluorethylene composites were characterized, in the case of the 1:1 composite,
      by a pyroelectric coefficient of 1.89 x 10(-4) cm(-2) K(-1), which was
      significantly higher than those determined under the same conditions for native
      anionic collagen and vinylidene fluoride-trifluorethylene.

PMID- 9527283
TI  - Migration resistant, blood-compatible plasticized polyvinyl chloride for medical
      and related applications.
AB  - Plasticized polyvinyl chloride (PVC), although not a blood-compatible polymer, is
      the material of choice for the manufacture of blood bags and hemodialysis tubing
      throughout the world. PVC is usually plasticized with di-(2-ethylhexyl phthalate)
      (DEHP) to impart flexibility and low temperature properties to the final product.
      DEHP belongs to a class of agents called hypolipidemic hepatocarcinogens, and it
      migrates in small quantities into the storage medium such as blood, plasma, or
      serum, resulting in a number of toxic effects. It has been shown that the
      migration resistance and blood compatibility of flexible PVC could be
      significantly improved by grafting polyethylene glycol (PEG), the most blood
      compatible polymer known today, onto the surface of flexible PVC by the classical
      Williamson ether synthesis reaction. The technique is simple and versatile enough
      to produce blood-compatible, migration resistant PVC surfaces for many medical
      applications. The method may also find use for preventing plasticizer migration
      from PVC cling films and polyvinylidene chloride films used extensively in food
      packaging.

PMID- 9527282
TI  - The controlled release of antibiotic by hydroxyapatite: anionic collagen
      composites.
AB  - Major problems with the treatment of osteomyelitis are associated with poor
      antibiotic distribution at the site of infection due to limited blood circulation
      to the skeletal tissue. Improved treatment procedures have been used in drug
      delivery systems that include bioceramics and natural and synthetic polymers.
      This work reports the development of anionic collagen:hydroxyapatite composite
      paste for sustained antibiotic release. Antibiotic release by the composite was
      characterized by two steps. In the first, 15.0+/-4.9% was released in the first 5
      h (n = 53) by a normal Fick diffusion mechanism. In the second step, only 16.8+/
      2.2% was released after 7 days. In conclusion, hydroxyapatite:anionic collagen
      composite can be an efficient support for sustained antibiotic release in the
      treatment of osteomyelitis because most of the antibiotic release may be
      associated with composite bioresorption, thus permitting antibiotic release
      throughout the healing process. Hydroxyapatite:anionic collagen paste showed good
      biocompatibility associated with bone tissue growth with material still being
      observed after 60 days from the time of implants.

PMID- 9527284
TI  - Assisted circulation for end-stage chronic heart failure.
AB  - Despite the trend in the use of electromechanical left ventricular assist devices
      (LVAD), the highly compact, long lasting, and endurance characteristics of the
      new pneumatic system has its place in the treatment of end-stage chronic heart
      failure. The ProCor Model 1 LVAD has an implantable pump which is small in size
      and has a double pusher plate design. The portable power pack is small, too. It
      is easy to carry, and it is synchronized to the ECG to pump during the patient's
      diastolic period. Constant driving conditions are set as follows: frequency rate,
      60 bpm; systolic percentage, 25 (250 ms); dP/dt, 1,800 (45 ms) mm Hg.s; and
      driving pressure, 250 mm Hg to have a basic 3.500 L/min pump output for prolonged
      circulatory assistance. The 6 mm internal diameter (ID) percutaneous multipurpose
      pneumatic tube contains within its wall both a spiral of MP35N alloy wire
      connected to the myocardial lead for ECG sensing and a spiral serving as mass
      ready to be used for cardiac pacing with an external pacemaker when necessary.
      The aortic porcine bioprosthesis maintains the aortic root and the sinus ridge.

PMID- 9527285
TI  - Availability and limits of intermediate cardiovascular technology.
AB  - Cardiovascular technology has been applied in the treatment of various diseases
      in Indonesia since its development in the late 1970s. Medical experts who have
      completed their training abroad began to implement their knowledge in
      cardiovascular service while a multifactorial limitation occurred in the country.
      The major limiting factor is still the country's infrastructure, which should
      support the treatment measures in modern cardiovascular technology. Other
      limiting factors concern nonmedical subjects, e.g., ethics, beliefs, religion,
      and the financial and basic organization of organ transplantation. Organ
      replacement started with artificial kidney/hemodialysis in the late 1970s, and
      was successfully carried out together with the further commencement of living
      related donor renal transplantation. Development of cardiac surgery with
      extracorporeal circulation gave rise to the stimulation of animal trials of
      cardiac transplant, pancreas transplant, and other subsets of organ
      transplantation. With the increasing modus of modernization, major hospitals in 3
      large cities have shown increasing needs for organ transplant, and, parallel to
      that, the increasing number of potential organ donors, the cause of death
      dominated by brain death resulting from traffic accidents. The emerging need for
      liver and cardiopulmonary transplants has also been observed during the last 5
      years, despite the improvement of general health care. However, similar to many
      Asian countries, because of religious and cultural considerations, it may be
      difficult to find donors whose relatives are willing to donate organs from their
      deceased relatives, especially for heart, lung, liver, and pancreas transplants.
      Alternative methods for artificial organs should receive more emphasis. We
      present the activities which have been established so far and how we should cope
      with the question of how present technology brings answers to the needs of organ
      transplant and artificial organs. Some innovative steps that we have made will be
      outlined.

PMID- 9527286
TI  - beStent--the serpentine balloon expandable stent: review of mechanical properties
      and clinical experience.
AB  - The objective of this study was to present the engineering and clinical aspects
      of a new balloon expandable coronary stent. A new tubular, serpentine design
      stainless steel balloon-expandable stent, the beStent, was designed based on
      clinical requirements for stents and has been clinically evaluated in multiple
      sites. The stent is featured by terminal gold markers and rotational junctions
      that assure no shortening upon expansion and lead to orthogonal locking,
      maximizing radial strength. In terms of methods and results, the stent was
      clinically evaluated in the framework of a pilot evaluation in a variety of
      lesion types. The short- and long-term results evaluated during the course of the
      beStent multicenter pilot evaluation and in our single center study are reported.
      A variety of patients were included, including patients with long complex
      lesions, restenosis lesions, and total occlusions. Short-term clinical success
      with stenting was achieved in more than 97% of the cases. Subacute thrombosis was
      low in 1% of the cases. Clinical restenosis rates were acceptable with an overall
      85% 6 month event free survival. In conclusion, the mechanical features of the
      stent providing its flexibility, scaffolding properties, radial strength, and
      absence of shortening were tested in a clinical study, showing that it is safe
      and effective for treating simple as well as long and complex lesions associated
      with coronary disease with a relatively low rate of complications.

PMID- 9527287
TI  - Implantable control, telemetry, and solar energy system in the moving actuator
      type total artificial heart.
AB  - The moving actuator type total artificial heart (TAH) developed in the Seoul
      National University has numerous design improvements based upon the digital
      signal processor (DSP). These improvements include the implantability of all
      electronics, an automatic control algorithm, and extension of the battery run
      time in connection with an amorphous silicon solar system (SS). The implantable
      electronics consist of the motor drive, main processor, intelligent Li ion
      battery management (LIBM) based upon the DSP, telemetry system, and
      transcutaneous energy transmission (TET) system. Major changes in the implantable
      electronics include decreasing the temperature rise by over 21 degrees C on the
      motor drive, volume reduction (40 x 55 x 33 mm, 7 cell assembly) of the battery
      pack using a Li ion (3.6 V/cell, 900 mA.h), and improvement of the battery run
      time (over 40 min) while providing the cardiac output (CO) of 5 L/min at 100 mm
      Hg afterload when the external battery for testing is connected with the SS (2.5
      W, 192.192, 1 kg) for the external battery recharge or the partial TAH drive. The
      phase locked loop (PLL) based telemetry system was implemented to improve
      stability and the error correction DSP algorithm programmed to achieve high
      accuracy. A field focused light emitting diode (LED) was used to obtain low light
      scattering along the propagation path, similar to the optical property of the
      laser and miniature sized, mounted on the pancake type TET coils. The TET
      operating resonance frequency was self tuned in a range of 360 to 410 kHz to
      provide enough power even at high afterloads. An automatic cardiac output
      regulation algorithm was developed based on interventricular pressure analysis
      and carried out in several animal experiments successfully. All electronics have
      been evaluated in vitro and in vivo and prepared for implantation of the TAH.
      Substantial progress has been made in designing a completely implantable TAH at
      the preclinical stage.

PMID- 9527288
TI  - Electromechanical unit helps artificial heart.

PMID- 9527289
TI  - Ethics of the allocation of highly advanced medical technologies.
AB  - The disproportionate distribution of financial, educational, social, and medical
      resources between some rich countries of the northern hemisphere and less
      fortunate societies creates a moral challenge of global dimension. The
      development of new forms of highly advanced medical technologies, including
      neoorgans and xenografts, as well as the promotion of health literacy and
      predictive and preventive medical services might reduce some problems in
      allocational justice. Most governments and the World Health Organization (WHO)
      reject financial and other rewards for living organ donors thus indirectly
      contributing to the development of black markets. A societal gratuity model
      supporting and safeguarding a highly regulated market between providers and
      recipients of organs might provide for better protection of those who provide
      organs not solely based on altruistic reasons. The moral assessment of global
      issues in allocation and justice in the distribution of medical technologies must
      be increased and will have to be based on the principles of self determination
      and responsibility, solidarity and subsidiarity, and respect for individual
      values and cultural traditions.

PMID- 9527290
TI  - Endosseal cylindric implants: experience from 2nd Dental Clinic, Brno, Czech
      Republic.

PMID- 9527291
TI  - Psychosocial problems presented by patients with somatic reasons for encounter:
      tip of the iceberg?
AB  - BACKGROUND: Health-affecting psychosocial problems are inherent in general
      practice, present among one-third of the patients and constituting between 3 and
      13% of reasons for encounter. Such problems are not always presented, and often
      overlooked by the doctors. OBJECTIVES: We aimed to describe the frequency of
      psychosocial problems presented to the doctor by patients with somatic reasons
      for encounter, as a proportion of the patients' existing health-affecting
      problems, and to explore whether characteristics of the doctor, the patient,
      their relationship or reason for encounter influence the presentation of
      problems. METHODS: A questionnaire survey of 1401 consecutive patients visiting
      89 Norwegian GPs mapped the prevalence of nine commonly occurring psychosocial
      problems and the frequency by which they were disclosed during the consultation.
      RESULTS: From 21% (loneliness) to 59% (occupational stress) of problems were
      disclosed to the doctors. Reason for encounter was the only factor to influence
      the disclosure from male patients, while reason for encounter, educational level
      and income source of the patient, gender of the doctor, and the doctor's previous
      general knowledge of the patient influenced the disclosure from female patients.
      CONCLUSIONS: Less than half of health-affecting psychosocial problems are
      disclosed to GPs by patients with somatic reasons for encounter. Occupational
      stress is disclosed more often than other psychosocial problems. Female patients
      disclose non-occupational problems more often than male patients, especially if
      they know the doctor or if the doctor is a woman. Symptoms from the
      musculoskeletal system are the reasons for encounter most often preceding the
      disclosure of psychosocial problems.

PMID- 9527292
TI  - The use of a back class teaching extension exercises in the treatment of acute
      low back pain in primary care.
AB  - BACKGROUND: Back extension exercises are commonly recommended to treat acute low
      back pain. Evidence of their beneficial effect is, however, weak. OBJECTIVES: We
      aimed to demonstrate a benefit of teaching back extension exercises in addition
      to usual GP care for acute low back pain. METHODS: Patients with acute simple low
      back pain of less than 28 days duration, presenting to a GP, were randomized
      either to attend a back class or to receive conventional management. Outcome was
      measured using changes in the Oswestry disability score and visual analogue pain
      scale (VAS) on six occasions during 1 year and also a VAS and patient assessment
      of degree of disability during the previous 6 months at 1 year. RESULTS: Seventy
      five patients were recruited. The principal outcome measures showed no difference
      between the two groups. The treatment group reported less chronic disability at 1
      year (50% versus 14%, P < 0.007). CONCLUSIONS: A treatment effect has not been
      demonstrated, but some patients who would otherwise have reported mild pain were
      pain free after 1 year. This approach to treating back pain has not been shown to
      be effective. More much larger studies, with more intensive treatment, are
      required in order to decide whether physical therapy in primary care is
      beneficial as treatment for acute back pain.

PMID- 9527293
TI  - The predictive value of influenza symptomatology in elderly people.
AB  - OBJECTIVE: We aimed to determine the complex of symptoms which has the highest
      predictive value for the diagnosis of influenza. METHOD: A questionnaire study
      with questions regarding the symptomatology of influenza among patients aged 60
      and older (n = 1838). Thirty-four participating GPs recorded the symptomatology
      of patients who came to their general practice with influenza-like complaints.
      The validity of the diagnostic conclusion of the GP, as well as the diagnostic
      validity of the criteria of the International Classification of Health Problems
      in Primary Care (ICHPPC-2) and the Sentinel Stations in The Netherlands, was
      determined with the help of the predictive value and odds ratio, using
      serologically confirmed influenza as the gold standard. The same method was used
      to determine which complex of symptoms has the highest predictive value for
      influenza. The results were verified using logistic regression analysis. RESULTS:
      The predictive value of the diagnostics of the GP amounted to 35%. The predictive
      values of the diagnostics according to the criteria of the two classification
      methods were 24% (Sentinel Stations) and 18% (ICHPPC-2). Of the individual
      symptoms, the combination of fever, coughing and acute onset had the highest
      predictive value (30.3%) for the diagnosis of influenza. CONCLUSION: It is
      recommended that the criteria of the Sentinel Stations in The Netherlands and the
      ICHPPC-2 be adapted in the following way: influenza is likely if, out of the
      entire complex of symptoms, at least fever, coughing and an acute onset occur.

PMID- 9527294
TI  - 'Inappropriate' attenders at accident and emergency departments I: definition,
      incidence and reasons for attendance.
AB  - BACKGROUND AND OBJECTIVES: Significant numbers of patients refer themselves to
      A&E departments for conditions which are neither accidents nor emergencies,
      relatively few of which require specific hospital treatment. These patients and
      their conditions have been described as 'inappropriate'. The objective of this
      paper is to review research relating to the definition, incidence and reasons for
      attendance of 'inappropriate' attenders. There is no accepted practical
      definition of what constitutes an 'appropriate' attender to an A&E department nor
      of what constitutes an 'emergency'. It is therefore not surprising that there is
      enormous variability (from 6 to 80%) regarding the proportion of visits judged to
      be inappropriate. All definitions rely completely on implicit and subjective
      judgements to determine appropriateness. The decision making of patients in
      opting to attend accident and emergency departments in preference to consulting
      their GP is complex, involving an interplay of social, psychological and medical
      factors. CONCLUSIONS: An analysis of reported work suggests that the most
      important factors are the perceived appropriateness of the condition for A&E, A&E
      accessibility and GP availability. A major deficiency in the available research
      is that patients have been retrospectively labelled as 'inappropriate' by medical
      personnel on the basis of the results of patient assessment and treatment. This
      review suggests that definitions and putative management strategies must consider
      the social and psychological context of the patients' decisions to attend.

PMID- 9527295
TI  - 'Inappropriate' attenders at accident and emergency departments II: health
      service responses.
AB  - BACKGROUND: Health services have responded to perceived 'inappropriate' attenders
      at accident and emergency (A&E) departments in three ways. Firstly, they have
      responded by attempting to decrease the numbers of patients attending A&E
      departments. There is little evidence supporting the efficacy of such policies.
      Secondly, they have responded by referring inappropriate attenders to another
      site. Research indicates that whilst such referral may be feasible, resultant
      decreases in departmental workloads have yet to be demonstrated. Patient outcome
      has also to be determined. Thirdly, by performing triage of attenders they
      provide care appropriate to their needs. Sessional GPs working in A&E departments
      manage non-emergency A&E attenders safely and use fewer resources than do usual
      A&E staff. Long-term effects on health-seeking behaviour and patient perception
      of the distinction between primary care services have yet to be determined.
      CONCLUSIONS: Rather than vainly attempting to make the patients appropriate to
      the service, future initiatives should concentrate on making the A&E service more
      appropriate to the patient.

PMID- 9527297
TI  - Patient attitudes to over-the-counter drugs and possible professional responses
      to self-medication.
AB  - BACKGROUND: There is a paucity of research about patients' attitudes towards
      their doctor's recommending over-the-counter (OTC) remedies or about how patients
      respond to the doctor's suggestion to try an OTC remedy. OBJECTIVES: The aim of
      this study was to ascertain the attitudes of patients to OTC drugs. METHODS: 505
      consecutive patients from each of six participating practices filled in a
      questionnaire. RESULTS: A total of 2765 (91.3%) patients responded. The responses
      from 2624 patients were from adults and are presented here. Based on the number
      of valid responses to each question, 53.8% of these patients were exempt from
      prescription charges, 55.1% took regular prescribed medication and 24.6% stated
      that they used OTC remedies regularly. There were generally positive attitudes to
      doctors enquiring about prior OTC use as well as to doctors making OTC
      recommendations in the consultation. However, patients expressed fairly negative
      attitudes towards pharmacists making generic substitutions and were even more
      hostile to the idea that pharmacists should make therapeutic substitutions.
      CONCLUSION: In conclusion, GPs should consider asking their patients regularly
      about their use of OTC medicines and also consider recommending OTC use if this
      is cheaper than FP10s. However, the public at present do not appear to be
      prepared for interventions by the pharmacist.

PMID- 9527296
TI  - Over-the-counter emergency contraception: a feasible option.
AB  - BACKGROUND: The high number of unintended pregnancies and terminations in Britain
      indicates that women who could use emergency contraception do not. Knowledge of
      access to sources of emergency contraception is limited. Oral administration of
      combined oestrogen-progestogen is safe and does not require routine physical
      administration, and there are proposals to re-regulate this from a prescription
      only medicine to a pharmacy medicine, available over the counter in community
      pharmacies under the supervision of a pharmacist. OBJECTIVES: We aimed to
      demonstrate that the availability of combined, oral oestrogen-progestogen under
      the supervision of the community pharmacist would be safe and effective. METHOD:
      Guidelines were developed by a multidisciplinary group incorporating pharmacists,
      GPs, a pharmacologist and a consultant in family planning. The guidelines were
      based on published evidence, where possible. CONCLUSION: Guidelines have been
      developed to accompany the provision of combined, oral oestrogen-progestogen
      which demonstrate that over-the-counter availability could be a safe and
      effective method of reducing the number of unwanted pregnancies in Britain.

PMID- 9527298
TI  - Real-patient evaluation of communication skills teaching for GP registrars.
AB  - BACKGROUND: Five thousand eight hundred and eighty-five patient-completed
      questionnaires were used to evaluate the effectiveness of an interpersonal skills
      module designed for a vocational training programme for GPs. OBJECTIVES: It was
      anticipated that patient-based assessments would detect a significant improvement
      in the interpersonal skills of GP Registrars who undertook the module. METHOD: A
      quasi-experimental design using an intervention and control group (comprising 68
      GP Registrars) was used to monitor the outcomes of the interpersonal skills
      module. RESULTS: Patient ratings of interpersonal skills were significantly
      higher for those GP Registrars who participated in the interpersonal skills
      module. CONCLUSIONS: Patient-based assessments are a useful evaluation method for
      assessing the quality of the doctor-patient relationship.

PMID- 9527299
TI  - Mixed feelings: satisfaction and disillusionment among Australian GPs.
AB  - BACKGROUND AND AIMS: Medical practitioners' satisfaction with their work impacts
      on quality of care for their patients and on their own sense of fulfillment.
      Reforms introduced in the early 1990s into Australian general practice have led
      to concerns over the morale of GPs. This study examines satisfaction and
      dissatisfaction of GPs with regard to the reform strategy. METHOD: GPs throughout
      Australia were approached via a popular GP magazine to express their views in a
      questionnaire comprising closed-end and open-ended questions enquiring about
      satisfaction with their current role and sources of satisfaction (and
      dissatisfaction) of working in general practice. Factor analysis was used to
      identify different sources of satisfaction (and dissatisfaction), which were
      intercorrelated and which together represented underlying factors. Logistic
      regression modelling was used to determine which sources were most strongly
      associated with being satisfied (or not satisfied), and to explore GP
      characteristics associated with satisfaction. RESULTS: A total of 2186
      questionnaires were returned, representing the opinions of 14-18% of Australian
      GPs. Two-thirds (68%) of respondents reported being satisfied, most frequently
      with the variety of work and establishing relationships with patients and their
      families. Six satisfaction factors were identified on factor analysis, the most
      important characterizing social and interpersonal roles. Leading sources of
      dissatisfaction related to perceived interference by the government. Six
      dissatisfaction factors were identified on factor analysis, the most important
      characterizing governmental issues. However, on logistic regression other sources
      of dissatisfaction (reflecting disillusionment) were most strongly associated
      with not being satisfied. CONCLUSIONS: The main sources of satisfaction are those
      which typify the long-term caring role of the community GP. While the reform
      strategy aimed to address problems with the organization and financing of general
      practice, the resulting intervention is the focus of dissatisfaction. Among
      dissatisfied GPs these attitudes may arise primarily from a sense of
      disillusionment.

PMID- 9527300
TI  - Screening of depression in patients with chronic medical diseases in a primary
      care setting.
AB  - BACKGROUND: Patients with chronic medical diseases may have depression that is
      not recognized by their primary care physicians. OBJECTIVES: We aimed to examine
      the application of Zung's Self-Rating Depression Scale (SDS) in the screening of
      depression in primary care patients with chronic medical diseases in a Chinese
      population. METHODS: We studied 268 patients with chronic medical diseases in the
      Family Medicine Outpatient Clinic using a structured questionnaire including
      basic demographic data, a Chinese version of the SDS and a rating for the self
      perceived severity of physical condition. The severity of chronic medical
      diseases was assessed by the authors using the Duke University Severity of
      Illness Scale from a chart audit. Fifty patients were randomly selected for a
      diagnostic interview according to the DSM-IV criteria. The construct validity and
      internal consistency reliability, sensitivity and specificity of the SDS were
      examined. RESULTS: The results revealed that the SDS has good construct validity
      and internal consistent reliability in the evaluation of depression in Chinese
      patients with chronic medical diseases. A cut-off point of 55 had a sensitivity
      of 66.7% and a specificity of 90.0%. Depressed patients reported more cognitive
      symptoms than depressed affect and physical symptoms. Female patients had more
      severe depressed affect than male patients, but males had more prominent diurnal
      variation of mood than females. CONCLUSIONS: We concluded that SDS can be a good
      screening tool for depression in Chinese patients with chronic medical diseases.
      Owing to constraints in the expression of sexual desire in the Chinese, elderly
      subjects tended to report loss of libido in the response to the SDS.

PMID- 9527301
TI  - Qualitative methods: beyond the cookbook.
AB  - BACKGROUND: Qualitative methods appear increasingly in vogue in health services
      research (HSR). Such research, however, has utilized, often uncritically, a
      'cookbook' of methods for data collection, and common-sense principles for data
      analysis. RESULTS AND CONCLUSIONS: This paper argues that qualitative HSR
      benefits from recognizing and drawing upon theoretical principles underlying
      qualitative data collection and analysis. A distinction is drawn between problem
      orientated and theory-orientated research, in order to illustrate how problem
      orientated research would benefit from the introduction of theoretical
      perspectives in order to develop the knowledge base of health services research.

PMID- 9527302
TI  - Trials which randomize practices I: how should they be analysed?
AB  - BACKGROUND: In some general practice intervention trials, patients must be
      randomized in practices rather than individually, and this must be taken into
      account in the analysis. OBJECTIVES: In this article we aim to show how failure
      to do this may lead to spurious statistical significance and CIs which are
      narrower than they should be, and to describe the use of summary measures for
      each practice as a simple method of analysis. METHOD: The statistical issues are
      demonstrated by an example of a trial in general practice. DISCUSSION: The choice
      of unit of analysis will be most important where there are large numbers of
      patients recruited from each practice or a high degree of variability between
      practices.

PMID- 9527303
TI  - Trials which randomize practices II: sample size.
AB  - BACKGROUND: When practices are randomized in a trial and observations are made on
      the patients to assess the relative effectiveness of the different interventions,
      sample size calculations need to estimate the number of practices required, not
      just the total number of patients. OBJECTIVE: Our aims were to introduce the
      methodology for appropriate sample size calculation and discuss the implications
      for power. METHOD: A worked example from general practice is used. DISCUSSION:
      Designs which randomize practices are less powerful than designs which randomize
      patients to intervention groups, particularly where a large number of patients is
      recruited from each practice. Studies which randomize few practices should be
      avoided if possible, as the loss of power is considerable and simple
      randomization may not ensure comparability of intervention groups.

PMID- 9527304
TI  - Selections from current literature: pharmacological treatment of obesity.

PMID- 9527305
TI  - Velopharyngeal function in nonsyndromic cleft palate: relevance of surgical
      technique, age at repair, and cleft type.
AB  - OBJECTIVE: The goal of this study was to determine the relative importance of
      surgical technique, age at repair, and cleft type for velopharyngeal function.
      DESIGN: This was a retrospective study of patients operated on by two surgeons
      using different techniques (von Langenbeck and Veau-Wardill-Kilner [VY]) at
      Children's Hospital, Boston, MA. PATIENTS: We included 228 patients who were at
      least 4 years of age at the time of review. Patients with identifiable syndromes,
      nonsyndromic Robin sequence, central nervous system disorders, communicatively
      significant hearing loss, and inadequate speech data were excluded. MAIN OUTCOME
      MEASURE: Need for a pharyngeal flap was the measure of outcome. RESULTS:
      Pharyngeal flap was necessary in 14% of von Langenbeck and 15% of VY repaired
      patients. There was a significant linear association (p = .025) between age at
      repair and velopharyngeal insufficiency (VPI). Patients with an attached vomer,
      soft cleft palate (SCP), and unilateral cleft lip/palate (UCLP) had a 10% flap
      rate, whereas those with an unattached vomer, hard/soft cleft palate (HSCP), and
      bilateral cleft lip/palate (BCLP) had a 23% flap rate (p = .03). Age at repair
      was critical for the unattached-vomer group (p = .03) but was not statistically
      significant for the attached-vomer group (p = .52). CONCLUSIONS: Surgical
      technique was not a significant variable either in aggregate or for the Veau
      types. Patients in the earliest repair group (8-10 months) were the least likely
      to require a pharyngeal flap. Early repair was more critical for HSCP and BCLP
      patients. There was no correlation between velopharyngeal insufficiency and Veau
      hierarchy. The attached vomer/levator muscle complex may be a more important
      predictor of surgical success than the anatomic extent of cleft.

PMID- 9527306
TI  - An anatomic study of the tensor veli palatini and dilatator tubae muscles in
      relation to eustachian tube and velar function.
AB  - In a gross anatomic study of 20 sides in 16 human head specimens, the tensor veli
      palatini, the dilatator tubae, and the tensor tympani muscles were studied. The
      tensor veli palatini was observed to insert onto the anterior one-third of the
      pterygoid hamulus, whereas the dilatator tubae rounded the middle one-third of
      the pterygoid hamulus without an insertion. Thus, the dilatator tubae, not the
      tensor veli palatini, could serve to tense the anterior velum. An insertion from
      the superior pharyngeal constrictor muscle onto the posterior one-third of the
      hamulus could provide a curbing function for the dilatator tubae muscle. Adipose
      tissue, located at the hamulus, could provide lubrication for the tendinous
      fibers of the dilatator tubae as they round the hamulus. The dilatator tubae was
      observed to attach to the hook of the eustachian tube and is accepted as the
      tubal dilator. Observed on 13 of 20 sides in 11 specimens, the bulk of the
      dilatator tubae remained distinct from the tensor veli palatini despite a
      connective tissue alliance and intermingling of some muscle fibers. On 5 of 20
      sides in 5 specimens, fibers of the dilatator tubae intermingled extensively with
      the tensor veli palatini. Of the 20 dilatator tubae muscles dissected, 2 were
      observed to be deficient. The tensor veli palatini was observed to be continuous
      with the tensor tympani. Full color versions of the figures are available at the
      following website: http://www.shc.uiowa.edu/papers/tensor/.

PMID- 9527307
TI  - Craniofacial morphology in adult patients with unoperated complete bilateral
      cleft lip and palate.
AB  - OBJECTIVE: This report is a retrospective study that compares the craniofacial
      morphology of adult subjects with unoperated bilateral complete cleft lip and
      palate (BCLP) with that of a noncleft group. METHODS: The study was performed on
      standardized lateral cephalograms obtained at the Hospital for Research and
      Rehabilitation of Cleft Lip and Palate, University of Sao Paulo, Brazil. The
      research group consisted of 28 subjects (20 males, 8 females) with unoperated
      BCLP, ranging in age from 15 to 41 years. The control group was matched to the
      cleft group with regard to gender and age. The findings were analyzed on the
      basis of the two-way analysis of variance (ANOVA) for cleft and gender. RESULTS:
      The most striking difference between the groups was the extremely prominent
      premaxilla in the cleft group that gave the BCLP face a very convex profile. The
      mandible exhibited a vertical growth pattern that resulted in a steep mandibular
      plane, an obtuse gonial angle and a long lower face height. The posterior face
      height was reduced. The cranial base dimensions were smaller, but there was no
      difference in cranial base angulation. CONCLUSIONS: These findings confirm that
      in subjects with unoperated BCLP, the initial characteristics of the cleft
      malformation persist during growth.

PMID- 9527308
TI  - A cephalometric evaluation of craniofacial morphology in familial dysautonomia.
AB  - OBJECTIVE: The purpose of this study was to delineate the craniofacial and
      dentoalveolar morphology of patients with familial dysautonomia (FD) in order to
      contribute to the understanding of the association between progressive sensory
      and autonomic neuropathy and the characteristic appearance of the dysautonomic
      face. PATIENTS: The study group comprised 32 patients with FD (15 females and 17
      males; mean age 10.8 years, SD 3.5 years, range 5.8-19.8 years). DESIGN: Lateral
      cephalograms from each patient were traced twice. The means of the two
      measurements were compared with homologous cephalometric normal values of ethnic
      specific and classical norms from the literature. RESULTS: In some parameters,
      the craniofacial morphology of the FD group was significantly different from the
      classical norms. There was a pronounced retrognathism in the mandible and a steep
      mandibular plane angle. The skeletal features of FD patients more closely
      resembled those of their ethnic group, although they were more retrognathic, and
      the mandibular growth axis was more horizontal. The incisors of these patients
      were more retropositioned and retroclined than were those of their healthy
      counterparts. CONCLUSIONS: The results suggest an insufficiency of the expected
      dentoalveolar compensatory mechanism that usually helps to bridge skeletal
      discrepancies. It is postulated that the neuropathy is probably the important
      factor in the lack of this compensatory mechanism.

PMID- 9527309
TI  - Learning disability, school achievement, and grade retention among children with
      cleft: a two-center study.
AB  - OBJECTIVE: This study examined the prevalence of learning disability (LD), level
      of school achievement; and prevalence of grade retention by type of cleft and
      gender at two craniofacial centers. SETTING: The setting included two university
      based craniofacial centers. DESIGN/PATIENTS: Participants included 84
      consecutively evaluated patients from one center who were matched by cleft type,
      age, and gender with 84 patients evaluated at the second center. OUTCOMES: The
      outcomes included learning disability, school achievement, and grade retention.
      RESULTS: The results revealed that 46% of subjects with cleft had LD, 47% had
      deficient educational progress, and 27% had repeated a grade (excluding
      kindergarten) in school. Males with cleft palate only (CPO) had a significantly
      higher rate of LD than any other subject group. Males with CPO and females with
      cleft lip and palate (CLP) were more likely to repeat a grade in school than were
      females with CPO and males with CLP. CONCLUSIONS: Children with cleft are at risk
      for learning disability, low school achievement, and grade retention.

PMID- 9527310
TI  - Sensitivity of a method for the analysis of facial mobility. I. Vector of
      displacement.
AB  - OBJECTIVE: (1) To determine which facial landmarks show the greatest movement
      during specific facial animations and (2) to determine the sensitivity of our
      instrument in using these landmarks to detect putatively abnormal facial
      movements. DESIGN: Movements of an array of skin-based landmarks on five healthy
      human subjects (2 men and 3 women; mean age, 27.6 years; range, 26 to 29 years)
      were observed during the execution of specific facial animations. To investigate
      the instrument sensitivity, we analyzed facial movements during maximal smile
      animations in six patients with different types of functional problems. In
      parallel, a panel was asked to view video recordings of the patients and to rate
      the degree of motor impairment. Comparisons were made between the panel scores
      and those of the measurement instrument. RESULTS: Specific regions of the face
      display movement that is representative of specific animations. During the smile
      animation, landmarks on the mid- and lower facial regions demonstrated the
      greatest movement. A similar pattern of movement was seen during the cheek puff
      animation, except that the infraorbital and chin regions demonstrated minimal
      movement. For the grimace and eye closure animations, the upper, mid-facial, and
      upper-lip regions exhibited the greatest movement. During eye opening, the upper
      and mid-facial regions, excluding the upper lip and cheek, moved the most, and
      during lip purse, markers on the mid- and lower face demonstrated the most
      movement. We used the smile-sensitive landmarks to evaluate individuals with
      functional impairment and found good agreement between instrument rankings based
      on the data from these landmarks and the panel rankings. CONCLUSION: The present
      method of three-dimensional tracking has the potential to detect and characterize
      a range of clinically significant functional deficits.

PMID- 9527311
TI  - Sensitivity of a method for the analysis of facial mobility. II. Interlandmark
      separation.
AB  - OBJECTIVE: This study demonstrates a method of quantifying facial movements based
      on distortions of the skin surface. DESIGN: Landmarks were identified on the
      faces of five healthy human subjects (2 men and 3 women; mean age, 27.6 years;
      range, 26 to 29 years), and the distortions were characterized by changes in the
      separation between 20 pairs of landmark distances during specific maximal facial
      animations: smile, lip purse, cheek puff, grimace, eye closure, and eye opening.
      Data were recorded with a video-based tracking system for a period of 3 seconds
      at a sampling rate of 60 Hz or frames per second. For each subject, we analyzed
      the change in the separation of 20 pairs of landmarks, of which the majority were
      bilaterally symmetrical and functionally active. RESULTS: Characteristic patterns
      of movement emerged for each animation. We found that smiling involved movements
      of the lateral orbital, circumoral, and chin regions; grimacing involved the
      inner orbital, lateral orbital, lateral nasal, and upper-lip regions; eye closure
      involved the inner orbital, lateral orbital, and, to a lesser degree, lateral
      nasal regions; eye opening involved the inner and lateral orbital regions; cheek
      puffing involved the cheek and lower-lip regions; and the lip purse animation
      involved the nasolabial, cheek, commissure, and lip regions. CONCLUSION: This
      measurement of distortion provided a quantitative estimate of facial movement,
      and this approach is especially applicable to patients with unilateral problems
      in which the patient can serve as his or her own control.

PMID- 9527312
TI  - Distribution patterns of primary and permanent dentition in children with
      unilateral complete cleft lip and palate.
AB  - OBJECTIVE: To investigate the distribution patterns of primary and permanent
      teeth in the cleft area and the numerical variation in teeth in unilateral
      complete cleft lip and palate (UCLP) patients. DESIGN: A survey of the dentition
      in UCLP patients. SETTING: Craniofacial Center, Chang Gung Memorial Hospital,
      Taipei, Taiwan. PATIENTS: 137 UCLP patients who met the following criteria: (1)
      have had at least one panoramic film taken, (2) the first panoramic film
      illustrates either primary or early mixed dentition. Evaluation of both permanent
      and primary dentition was available in 91 cases. MAIN OUTCOME MEASURES: Two
      evaluators performed independent evaluations of number and distribution of teeth
      in UCLP patients. The hypothesis that there are two odontogenic origins for
      maxillary lateral incisors was proposed to explain the occurrence of distribution
      patterns of dentition in the cleft area and to explain differences between
      primary and permanent dentition in UCLP patients. RESULTS: Four distribution
      patterns in the cleft area were identified in both the primary and the permanent
      dentition. In the primary dentition, placement of the lateral incisor distal to
      the alveolar cleft was the predominant pattern (pattern y, 82.4%), followed by
      absence of the cleft side maxillary lateral incisor (pattern ab, 9.9%), presence
      of one tooth on each side of the alveolar cleft (pattern xy, 5.5%), and placement
      of the lateral incisor mesial to the alveolar cleft (pattern x, 2.2%). In the
      permanent dentition, the most common pattern was the absence of the maxillary
      lateral incisor on the cleft side (pattern AB, 51.8%), followed by lateral
      incisor placement distal to the alveolar cleft (pattern Y, 46%), lateral incisor
      placement mesial to the alveolar cleft (pattern X, 1.5%) and the presence of one
      tooth on each side of the alveolar cleft (pattern XY, 0.7%). The discrepancy
      between the distribution patterns of primary dentition and permanent dentition
      successors is 57.1%. Variations in tooth number in both primary and permanent
      dentition of UCLP patients occurred most often in the cleft area. Abnormalities
      in the number of teeth (hypodontia or hyperdontia) outside the cleft area were
      more common in the permanent dentition than in the primary dentition (24.1%
      versus 4.4%). CONCLUSIONS: Four distribution patterns in the cleft area were
      identified in both sets of dentition. Our findings of distribution patterns in
      UCLP patients support the hypothesis that there may be two odontogenic origins
      for maxillary lateral incisors. Clinicians involved in managing the dentition of
      UCLP patients should consider the high frequency of numerical variation both in
      and outside the cleft area before starting dental treatment.

PMID- 9527313
TI  - Characteristics of jaw growth in cleidocranial dysplasia.
AB  - OBJECTIVE: The purpose of this pilot study was to assess craniofacial morphology
      in young and adult individuals with cleidocranial dysplasia (CCD). DESIGN:
      Craniofacial morphology in young individuals (primary dentition) and in young
      adults was compared with control data using ratios and angles obtained from
      lateral head films. SETTING: The CCD individuals were referred to the Center for
      Craniofacial Anomalies for diagnostic workup and treatment recommendations.
      SUBJECTS: The sample consisted of 14 Caucasians. The inclusion criterion for the
      young, prepubertal group (A) was complete primary dentition, and for the adult,
      postpubertal group (B), the eruption of all four first molars was required.
      INTERVENTIONS: No treatment other than extraction or surgical removal of selected
      primary or supernumerary teeth was performed. RESULTS: Both groups showed
      significantly smaller anterior upper face height compared with controls. Group B
      subjects demonstrated significantly smaller face height values than the controls
      in the A point-nasion-B point (ANB) angle, facial axis, mandibular plane angle,
      palatal plane/mandibular plane angle, and gonial angle. No significant
      differences were found between group A individuals and the controls for these
      measurements. The older group had shorter anterior lower face height compared
      with both anterior upper face height and posterior lower face height.
      CONCLUSIONS: Whereas young CCD subjects showed relatively normal jaw proportions
      and morphology of the mandible, older CCD individuals tended to have short lower
      face height, acute gonial angle, anterior inclination of the mandible, and
      mandibular prognathism. These differences can be attributed to pronounced
      horizontal mandibular growth resulting from lack of vertical maxillary growth and
      impaired eruption of permanent teeth.

PMID- 9527314
TI  - Multiple suture synostosis and increased intracranial pressure following repair
      of single suture, nonsyndromal craniosynostosis.
AB  - OBJECTIVE: Increased intracranial pressure, frequently associated with closure of
      multiple cranial sutures, has been reported to occur in 36% of cases following
      correction of syndromal craniosynostosis. Although much less common, multiple
      suture closure may occur following repair of single suture, nonsyndromal
      craniosynostosis and we present cases that concern two such children. RESULTS:
      Two children with nonsyndromal craniosynostosis, one metopic and one left
      coronal, underwent fronto-orbital advancement at age 3 months. At age 19 months
      and at age 5 years, respectively, both patients re-presented with headaches,
      decrease in head circumference percentile, and acceptable cosmetic outcome. Both
      had computerized tomographic evidence of multiple closed cranial sutures and
      increased intracranial pressure (ICP) (determined by monitoring). Both patients
      improved following a cranial expansion procedure. CONCLUSION: Delayed closure of
      multiple sutures and resultant increased ICP may occur following correction of
      nonsyndromal, single suture craniosynostosis. This may be more likely when the
      initial suture is contiguous with the facial sutures. Children should be followed
      for many years following craniosynostosis repair with cranial, neurologic, and
      possibly funduscopic examinations as well as head circumference measurements to
      detect delayed closure of cranial sutures.

PMID- 9527315
TI  - Comparison of craniofacial and dentoalveolar morphologies of three Japanese
      monozygotic twin pairs with cleft lip and/or palate discordancy.
AB  - OBJECTIVE: In this study, we analyzed the craniofacial and dentoalveolar
      morphologies of three pairs of monozygotic twins discordant for cleft lip and/or
      palate (CL/P) in order to evaluate the effects of environmental factors on growth
      and development. DESIGN: Craniofacial and dentoalveolar morphologies revealed by
      analyses of cephalograms and dental casts were compared for each pair of twins
      discordant for CL/P. SUBJECTS: In case 1, the subjects were 10-year-old male
      twins, one of whom had a repaired unilateral cleft lip and alveolus and one of
      whom had an unrepaired unilateral cleft lip. In case 2, the subjects were 13-year
      old female twins, one of whom had a repaired bilateral cleft lip and palate and
      one of whom had an unrepaired unilateral cleft lip. In case 3, the subjects were
      9-year-old female twins, one of whom had a repaired unilateral cleft lip and
      palate and one of whom had no cleft. RESULTS: Cephalometric analysis disclosed
      distinguished intrapair differences in the maxillary and mandibular morphologies
      in cases 2 and 3. However, the tooth axes of the incisors in operated subjects
      were consistently influenced in all three cases. Dental cast analysis indicated
      that the shapes and sizes of the alveolar and dental arches in the operated
      subjects were affected in case 2 and, more severely, in case 3, while they looked
      fairly similar in case 1. CONCLUSIONS: Cephalometric and dental cast analyses
      demonstrated characteristic intrapair differences between the twins discordant
      for CL/P according to each cleft type. These morphological differences indicate
      that surgical closure of clefts may have considerable effects on craniofacial and
      dentoalveolar growth and development in CL/P patients.

PMID- 9527316
TI  - In Vietnam, many congenital anomalies are believed to result from the scattering
      of defoliants, including dioxin.

PMID- 9527317
TI  - Assessment of visual acuity in adult patients with strabismic amblyopia: a
      comparison between the preferential looking method and different acuity charts.
AB  - PURPOSE: Grating acuity values obtained with preferential looking techniques do
      not correspond to test results obtained with letter charts. The aim of the study
      was to investigate the agreement between grating acuity and other acuity tests.
      METHODS: Twenty-eight adult patients with strabismic amblyopia were assessed with
      the preferential looking-method and other linear and single letter and symbol
      tests. RESULTS: Assessment with preferential looking regularly led to an
      overestimation of the acuity values, but between preferential looking and single
      optotypes there was a much better agreement. This is most likely due to
      'crowding' in strabismic amblyopia. A crowding ratio was calculated in the
      amblyopic eye, and crowding was found to be more prominent for comparisons of
      preferential looking with optotypes in rows, than for preferential looking and
      single optotypes. CONCLUSIONS: Strabismic amblyopia cannot be reliably identified
      with grating acuity. Preferential looking-testing is therefore of limited use as
      a screening method for the detection of amblyopia, but preferential looking could
      still be useful in the assessment and treatment.

PMID- 9527318
TI  - Nonsurgical and surgical methods of sclera reinforcement in progressive myopia.
AB  - PURPOSE: As shown by the clinical picture of progressive myopia, derangements in
      biomechanical properties of sclera may be more or less manifested. The study aims
      at the development of a discriminating approach to their correction. METHODS:
      Patients with the condition were given a sclera strengthening injection, in which
      a dose of liquid polymeric composition is injected under the Tenon's capsule on
      the scleral surface. After polymerization, the composition forms over the scleral
      surface a layer of elastic foamed gel. RESULTS: Complex experiments on 146 rabbit
      eyes showed that the injected material promotes collagen formation. Gradually
      dissolving, the gel stimulates the growth of connective tissue on the surface of
      the sclera, whose stress-strain parameters improve. A thorough clinical study of
      240 eyes of patients aged 8-25 years with progressive 6-10 D myopia showed that
      the refraction remained stable in 79.6% eyes 1 year after the sclera
      strengthening injection and in 52.9% cases 4-9 years after the sclera
      strengthening injection. At the same time, fellow intact eyes have shown,
      respectively, 40.3% and 13.3% of myopia stabilization, and 212 untreated eyes of
      the control group 26.0% and 11.1%, respectively. 612 children and adolescents
      with high myopia and a yearly progression of over 1.0 D were subjected to a
      scleroplastic operation. It was found that the myopia remained stable in 95.7%
      cases 1 year after the operation, and in 71.9%, 7 years after the operation. If
      myopia progression continued after a sclera strengthening injection or
      scleroplasty, a second procedure was performed. Second interventions were
      effected on 118 eyes of 102 patients, including 42 eyes where a sclera
      strengthening injection followed a sclera strengthening injection, 27 eyes where
      scleroplasty followed a sclera strengthening injection, 31 eyes where a sclera
      strengthening injection followed scleroplasty, and 18 eyes on which a second
      scleroplasty was performed. Second interventions provide a double decrease of
      myopia progression rate and, in 63% of patients, stop the progression altogether.
      CONCLUSION: It can be concluded that nonsurgical and surgical techniques of
      correcting the biomechanical properties of sclera for the treatment of
      progressive myopia as well as discriminative methods of determining the
      indications to these procedures have proven to be effective.

PMID- 9527319
TI  - Confocal microscopy using oblique sections for measurement of corneal epithelial
      thickness in conscious humans.
AB  - PURPOSE: Thickness measurements by confocal microscopy in conscious human
      subjects may be liable to error as a result of instability of the eye or
      instrument. Our aim was to evaluate a technique which was expected to be less
      sensitive to such problems. METHOD: Thickness of corneal epithelium was
      determined from oblique confocal sections through cornea. A contact lens of known
      thickness worn by subjects was used to calibrate images. RESULTS: There were two
      layers in images which could have corresponded to the stromal/epithelial
      interface. The mean result in each subject ranged from 38 to 53 microm using the
      more superficial layer and 46 to 60 microm using the deeper one. The smaller
      values gave the distance between the epithelial surface and the sub-epithelial
      nerve plexus and thus seemed to correspond to epithelial thickness. CONCLUSIONS:
      Measurements of epithelial thickness by our new method are comparable with
      results of earlier studies.

PMID- 9527320
TI  - Comparison of objective methods for quantifying the refractive effect of photo
      astigmatic refractive keratectomy using the MEL-60 excimer laser.
AB  - PURPOSE: To investigate the accuracy and precision of automated keratometry,
      automated refractometry, and computerized corneal topography in estimating the
      subjective refractive outcome of photo-astigmatic refractive keratectomy six
      months postoperatively. METHODS: Photo-astigmatic refractive keratectomy
      (Aesculap-Meditec, MEL-60 Excimer Laser) was performed on 26 eyes with a
      preoperative myopia ranging from -4.0 to 7.6 dioptres, and a naturally occurring
      astigmatism from 0.75 to 5.0 dioptres. Six months postoperatively refractive
      outcome was evaluated by automated keratometry, automated refractometry (Nikon
      NRK-8000), computerized topography (TMS-1), and subjective refraction. Estimate
      errors were computed as the difference between the change in subjective
      refraction and the change in automated keratometry, automated refractometry, and
      surface topography, respectively. Astigmatic changes were evaluated by the second
      harmonic component in the Fourier series analysis. RESULTS: Subjective spherical
      as well as cylindrical values were reduced significantly six months
      postoperatively. The estimate error (mean +/- one standard deviation) for
      automated keratometry was -1.26 +/- 0.72 dioptres for the spherical equivalent
      and -1.36 +/- 1.02 dioptres for the cylinder; for automated refractometry it was 
      0.78 +/- 0.91 dioptres for the spherical equivalent and -0.66 +/- 0.92 dioptres
      for the cylinder. The best estimates of subjective changes were obtained when the
      average of ring 2 and 3 of the topographic data was used: -0.15 +/- 0.82 dioptres
      for the spherical equivalent and -0.78 +/- 0.80 dioptres for the cylinder.
      CONCLUSIONS: The computerized topographer with the Fourier analysis was superior
      to automated keratometry and automated refractometry in estimating the subjective
      spherical refractive outcome and comparable to automated refractometry in
      estimating the subjective cylinder refractive outcome after photo-astigmatic
      refractive keratectomy.

PMID- 9527322
TI  - Measurement of thickness of retinal nerve fiber layer by scanning laser
      polarimetry and high-pass resolution perimetry in patients with primary open
      angle or normal-tension glaucoma.
AB  - PURPOSE: To evaluate the correlation between neural capacity, determined by high
      pass resolution perimetry, and thickness of the retinal nerve fiber layer,
      evaluated by scanning laser polarimetry, in patients with primary open-angle
      glaucoma or normal-tension glaucoma. METHODS: Thickness of the peripapillary
      retinal nerve fiber layer was measured by scanning laser polarimetry in 19 eyes
      of 19 patients with primary open-angle glaucoma and in 23 eyes of 23 patients
      with normal-tension glaucoma. There were no significant differences between the
      two groups in mean age, sex ratio, or mean neural capacity. RESULTS: Neural
      capacity was significantly correlated with thickness of the retinal nerve fiber
      layer in all 42 eyes (r = 0.31, P = 0.0429). Neural capacity was significantly
      correlated with thickness of the retinal nerve fiber layer in the eyes of
      patients with primary open-angle glaucoma (r = 0.60, P = 0.0061), but not in the
      eyes of patients with normal-tension glaucoma (r = 0.04; P = 0.8522). CONCLUSION:
      The degree of correlation between neural capacity determined by high-pass
      resolution perimetry and thickness of the retinal nerve fiber layer measured by
      scanning laser polarimetry appeared to differ in patients with primary open-angle
      glaucoma vs those with normal-tension glaucoma.

PMID- 9527321
TI  - Long-term supplementation with alpha-tocopherol and beta-carotene and age-related
      cataract.
AB  - PURPOSE: To study if long-term supplementation with alpha-tocopherol or beta
      carotene is associated with cataract prevalence and severity. METHODS: An end-of
      trial random sample of 1828 participants from the randomized, double-blind,
      placebo-controlled clinical trial the alpha-tocopherol, beta-carotene cancer
      prevention study. The alpha-tocopherol, beta-carotene cancer prevention study was
      originally designed to examine whether supplementation with alpha-tocopherol or
      beta-carotene would reduce the incidence of lung cancer in male smokers. The
      participants for this study lived in Helsinki City or Uusimaa province and were
      at entry to the alpha-tocopherol, beta-carotene cancer prevention study 50 to 69
      years old and smoked at least 5 cigarettes per day. They received alpha
      tocopherol 50 mg/day, beta-carotene 20 mg/day, a combination of the two, or
      placebo supplements for 5 to 8 years (median 6.6 years). Outcome measures were:
      cortical, nuclear, and posterior subcapsular cataract, differentiated and
      quantified with lens opacity classification system (LOCS II). Lens opacity meter
      provided a continuous measure of cataract density. RESULTS: Supplementation with
      alpha-tocopherol or beta-carotene was not associated with the end-of-trial
      prevalence of nuclear (odds ratio 1.1 and 1.2, respectively), cortical (odds
      ratio 1.0 and 1.3, respectively), or posterior subcapsular cataract (odds ratio
      1.1 and 1.0, respectively) when adjusted for possible confounders in logistic
      model. Neither did the median lens opacity meter values differ between the
      supplementation groups, indicating no effect of alpha-tocopherol or beta-carotene
      on cataract severity. CONCLUSION: Supplementation with alpha-tocopherol or beta
      carotene for 5 to 8 years does not influence the cataract prevalence among middle
      aged, smoking men.

PMID- 9527323
TI  - Topography of corneal grafts before and after penetrating keratoplasty.
AB  - PURPOSE: Refractive error after penetrating keratoplasty is a major clinical
      problem. The purpose of the present study was to investigate whether the
      topography of the donor cornea influence the topography of the graft after
      transplantation. METHODS: Twenty-five donor corneas were measured with a video
      keratograph (TMS-1): in situ and before and after organ culture. Clinical video
      keratographic images of the transplanted grafts were subsequently obtained one
      week, 1, 3, 6, 12, and 24 months after surgery. The central spherical equivalent
      power and corresponding regular and irregular astigmatic powers were computed.
      RESULTS: A statistically significant correlation between spherical equivalent
      central donor power and spherical equivalent central graft power after
      keratoplasty was found at all times up to two years after surgery. Only 13-50% of
      the variation in post-keratoplasty spherical graft power could, however, be
      explained by the donor graft power. Corresponding 95% confidence limits for
      prediction of post-keratoplasty power from donor graft power were approximately
      +/- 6.5 diopters. Post-keratoplasty regular or irregular corneal astigmatism did
      not correlate with astigmatism in the donor graft. CONCLUSION: Corneal donor
      graft spherical equivalent power does influence the spherical equivalent corneal
      power after keratoplasty, especially during the first months after surgery. The
      dependency is, however, not very strong and until other determinants of post
      keratoplasty corneal shape are known and controllable, 'power-typing' of donor
      corneas appears to be of limited clinical use.

PMID- 9527324
TI  - Vascular endothelial growth factor (VEGF) in normal human corneal epithelium:
      detection and physiological importance.
AB  - PURPOSE: Corneal neovascularization is a major challenge following chemical burns
      and corneal inflammation. The factors triggering corneal neovascularization
      involve various growth factors. In the release and control of these factors the
      regenerating tissue plays a decisive role. Only recently has vascular endothelial
      growth factor been shown to be involved in the basic events of retinal
      neovascularization. From the cornea current knowledge allows only for the
      statement that corneal epithelium could be able to produce vascular endothelial
      growth factor. The present study was designed to show the presence of vascular
      endothelial growth factor-like substances in the corneal epithelium of the normal
      eye in vivo. METHODS: Using specific antibodies to the N-terminus of human
      vascular endothelial growth factor indirect immuno-histochemistry was applied to
      sections of normal human corneal epithelium and to five sections of enucleated
      human eyes with a morphologically normal anterior segment. RESULTS: In all
      sections specific staining for vascular endothelial growth factor was found over
      the entire epithelium. Staining was most intense in the basal layer of epithelial
      cells. Only a weak staining was detectable in the cell layers closer to the
      surface. Here, however, the samples of corneal epithelium having been subject to
      traumatic erosion showed a slightly more intense staining than the sections from
      the undisturbed corneal tissue of whole globe sections. CONCLUSION: It was shown
      that vascular endothelial growth factor-like protein is present in the human
      corneal epithelium. Observed differences in the staining pattern could suggest
      that the expression of vascular endothelial growth factor might be enhanced due
      to ocular surface trauma. It is suggested that corneal epithel vascular
      endothelial growth factor might be an important factor in the cascade leading to
      the onset of corneal neovascularization.

PMID- 9527326
TI  - Indocyanine green videoangiography of angioid streaks.
AB  - PURPOSE: This study was performed to define the indocyanine green angiographic
      features of angioid streaks and associated posterior pole lesions and to compare
      them with fluorescein angiography. METHODS: Digital fluorescein and indocyanine
      green videoangiography was performed on 16 eyes of 8 patients with angioid
      streaks. RESULTS: Streaks were hyperfluorescent in 15, hypo- and hyperfluorescent
      in 1 of the 16 eyes with fluorescein angiography. Indocyanine green angiography
      showed hyperfluorescent streaks in 10 and hypofluorescent streaks in 6 eyes. Of
      the hyperfluorescent streaks, 6 had a hypofluorescent line between fluorescent
      edges and 4 were made up of numerous hyperfluorescent spots. Peau d'orange
      appearance was more evident in indocyanine green angiography as dark, round spots
      throughout the posterior pole. Fluorescein angiography confirmed the presence of
      well-defined choroidal neovascularization in 5 eyes. In one eye, occult choroidal
      neovascularization which was not evident on fluorescein angiography, became well
      demarcated on indocyanine green angiography. CONCLUSION: Indocyanine green
      angiographic features of angioid streaks are different from fluorescein
      angiography. Angioid streaks and peau d'orange are more evident with indocyanine
      green angiography.

PMID- 9527325
TI  - Indocyanine green angiography and transmission defects.
AB  - PURPOSE: Several reports have suggested that indocyanine green angiography is of
      value in identifying late hyperfluorescent subretinal tissue presumed to be
      choroidal neovascularization. However, fluorescein angiography may also reveal
      late hyperfluorescence from transmission defects caused by atrophy of the retinal
      pigment epithelium. We studied the indocyanine green angiographic characteristics
      of transmission defects to determine if indocyanine green angiography can
      differentiate choroidal neovascularization from the retinal pigment epithelium
      atrophy. METHODS: Indocyanine green angiograms of 23 eyes with geographic atrophy
      secondary to age-related macular degeneration and without any signs or history of
      choroidal neovascularization were reviewed. RESULTS: Indocyanine green
      angiography demonstrated late hypofluorescence of various degrees in the area of
      geographic atrophy. There was no evidence of late hyperfluorescence. CONCLUSION:
      Late hyperfluorescence evident on fluorescein angiography which can be caused by
      choroidal neovascularization or transmission defects is not seen in retinal
      pigment epithelium atrophy imaged by indocyanine green angiography. According to
      these results indocyanine green angiography is useful to differentiate occult
      choroidal neovascularization from areas of retinal pigment epithelium atrophy.

PMID- 9527327
TI  - Pulsatile ocular blood flow in untreated diabetic retinopathy.
AB  - PURPOSE: To measure the pulsatile component of total ocular blood flow in
      patients with untreated diabetic retinopathy. SUBJECTS AND METHODS: An adapted
      pneumotonometer attached to a slit-lamp biomicroscope. 82 age-matched subjects
      divided into 4 groups: non-diabetic controls (n = 22); diabetics with no clinical
      retinopathy (n = 20); background diabetic retinopathy (n = 20); pre
      proliferative/proliferative diabetic retinopathy (n = 20). RESULTS: The mean
      pulsatile ocular blood flow values were found to be increased in all grades of
      diabetic retinopathy (no retinopathy 818 microl/min, background 1015 microl/min,
      pre-proliferative/proliferative 1097 microl/min) compared to the control group
      (644 microl/min). These pulsatile ocular blood flow values were significantly
      higher (p<0.05) in the background and pre-proliferative/proliferative retinopathy
      groups compared to controls. Pulse volume and pulse amplitude were also higher in
      the diabetic subjects. Mean arterial blood pressure did not differ across the
      groups studied. CONCLUSION: Pulsatile ocular blood flow was found to be higher in
      diabetics compared to controls and appears to increase as the severity of
      retinopathy progresses. Such a hyperdynamic circulation may contribute to the
      pathogenesis of diabetic eye disease.

PMID- 9527328
TI  - A perimetric learner's index.
AB  - PURPOSE: Certain individuals need earlier perimetric experience before producing
      normal fields on automated static threshold perimetry. Mid-peripheral depressions
      and an unaffected central field are typical findings in such cases. We have
      devised a learner's index, to detect defect patterns that may be due to such
      perimetric inexperience. METHODS: The central visual field was partitioned into 5
      concentric zones and averages of deviations from the age-corrected normal
      threshold values were studied in each zone. The third test session in 74 randomly
      selected normal subjects provided an experienced reference material. Visual field
      results typical of normal individuals lacking perimetric experience were
      represented by the first field test obtained from each of 7 subjects ('learners')
      from the same group, who showed significant learning during three test sessions.
      A linear discriminant function, learner's index, was constructed that
      discriminates between typically experienced and typically inexperienced field
      results in normals. RESULTS: Average deviation from age-corrected normal
      threshold increased with increasing eccentricity in the learner's initial fields.
      Clinical examples illustrate the intended use of the new index. CONCLUSIONS: The
      learner's index highlights those first field tests from eyes with normal visual
      fields, that deviate significantly from a normal experienced result in the
      direction of a learner's result. Patients showing significant learner's index are
      candidates for repeated visual field testing.

PMID- 9527329
TI  - Induced astigmatism after 4 and 6 mm scleral tunnel incision. A randomized study.
AB  - PURPOSE: To study the surgically induced astigmatism after phacoemulsification
      through either a 4 or a 6 mm scleral tunnel incision by using multiple analyses
      of astigmatism. METHODS: 197 eyes from 186 patients scheduled for
      phacoemulsification between October 1992 and March 1994 were randomly assigned
      two different-sized incisions with follow-ups at 1 day, 1 week, 2 weeks, 1 month
      and 4 months after surgery. The surgically induced astigmatism was evaluated
      using at each follow-up: 1) The subtraction method, 2) vector analysis, 3) vector
      decomposition, 4) Cravy's vertical vector, 5) Naeser's polar values, and 6) the
      algebraic method. RESULTS: By subtraction, without regard to axis, the induced
      astigmatism 4 months after surgery was +0.04 D and +0.18 D in the 4 mm and the 6
      mm incision group, respectively. By vector analysis, the numerical value of the
      induced cylinder was stable one month after surgery at 0.61 D and 0.77 D in the 4
      mm and in the 6 mm group, respectively. However, cylinder orientation was not
      found stable until 4 months after surgery, where 94% and 96% of the surgically
      induced astigmatism (vector decomposition) was against-the-wound in the two
      groups, respectively. By Cravy's method, the mean induced astigmatism changed
      from -0.08 D to -0.32 D and from -0.42 D to -0.60 D between 1 and 4 months in the
      4 mm and the 6 mm group, respectively. Similar values were found with Naeser's
      method and with the algebraic method. CONCLUSION: We conclude the mean cylinder
      of the surgically induced astigmatism (vector analysis) to be stable 1 month
      after phacoemulsification with both the 4 mm and 6 mm scleral tunnel incision.
      However, the direction of the induced axis (vector decomposition) was still
      drifting between 1 and 4 months in both groups. These astigmatic changes were
      adequately described using vector analysis and vector decomposition.

PMID- 9527330
TI  - Video fluorescein angiography of the anterior eye segment in severe eye burns.
AB  - PURPOSE: Severe eye burns often result in extensive necrosis of the conjunctiva
      and episcleral tissue. Video fluorescein angiography was performed to reveal the
      perfusion of the anterior eye segment after severe eye burns. METHODS: A scanning
      laser ophthalmoscope was used for anterior segment fluorescein angiography in 12
      patients (14 eyes) with severe burns grade III-IV and in 7 healthy volunteers.
      RESULTS: Necrotic tissues occurred as non perfused areas and remained dark
      throughout the whole angiogram. In general, the borders from healthy to necrotic
      conjunctival tissue were sharply demarcated. Thus, the extent of scleral and
      limbal ischemia could be determined exactly. Injured vessels showed
      hyperfluorescence with late leakage. Damage of the subconjunctival tissue
      appeared as a deep weak fluorescence in the early angiography and exhibited
      patchy leakage in the late angiogram. CONCLUSIONS: Anterior segment angiography
      provides a basis for deciding the extent of surgical debridement of necrotic
      tissue in the acute phase of the burn. The determination of the extent of limbal
      and scleral ischemia may give useful information for early plastic-reconstructive
      procedures.

PMID- 9527331
TI  - Visual impairment in Swedish children. III. Diagnoses.
AB  - PURPOSE: To gain an overview of the spectrum of diagnoses among Swedish visually
      impaired children. METHODS: An epidemiological study of all known visually
      impaired children was made by review of medical records. RESULTS AND CONCLUSION:
      In all we found 2373 children, 0-19 years of age, with an age-specific prevalence
      of 10.9/10,000. The two largest diagnostic groups included neuro-ophthalmological
      and retinal diseases. The most frequent disorders were cerebral visual
      impairment, non-hereditary optic atrophy, retinal dystrophy (when regarded as a
      general entity), congenital hypoplasia of the optic nerve and congenital
      cataract. Nystagmus secondary to brain disorder, albinism, congenital nystagmus,
      retinopathy of prematurity and high myopia were also found in a considerable
      number of patients. The leading diagnoses in children with WHO-defined childhood
      blindness were non-hereditary optic atrophy, cerebral visual impairment and
      retinopathy of prematurity. A large proportion of the children, especially in the
      groups with neuro-ophthalmological disorders and malformations of the posterior
      segment had additional impairments, emphasizing the importance of a multi
      disciplinary approach when assessing multi-handicapped children.

PMID- 9527332
TI  - An outcome study of cataract surgery based on a national register.
AB  - PURPOSE: To test the viability of performing a national cataract outcome study
      with a national cataract register as a reference base. METHODS: Seven Swedish eye
      clinics participated. All patients operated during the month of January 1994 were
      included. The total number of patients was 605. RESULTS: This outcome study is
      based on few, but well defined parameters. On the basis of these measurements
      quality indicators are suggested that makes comparison between surgeons/clinics
      possible. CONCLUSION: Outcome studies are different from controlled clinical
      trials. They are less time consuming and designed to describe the outcome of
      surgery in daily practise. An outcome study of cataract surgery does not replace
      the careful monitoring of each patient at the clinical level, which is necessary
      for the development of new surgical technics and medical treatments. However, an
      outcome study can provide an overall quality description of cataract surgery in
      the daily practise of any given surgical unit.

PMID- 9527333
TI  - Evaluation of glaucoma patients referred to a university clinic during one year.
AB  - PURPOSE: In the spring of 1994, the post-referral waiting time for glaucoma
      patients at our institution was approximately 7 months. In an attempt to evaluate
      and possibly reduce this waiting time we compared the referral criteria to the
      actual treatment requirements of 472 patients admitted for glaucoma in 1995.
      RESULTS: 175 patients were referred as glaucoma suspects, 134 as chronic simple
      glaucoma, and 123 as capsular glaucoma. In addition, 40 patients were referred as
      other types of glaucoma. Elevated IOP was the main criterion for referral in 133
      (76%) of glaucoma suspects. The diagnosis of glaucoma could not, however, be
      confirmed in 54 (31%) glaucoma suspects. 93 (69%) patients with simple open angle
      glaucoma and 103 (84%) patients with capsular glaucoma were also referred because
      of IOP > or = 22 mmHg. Maximally tolerated medication was not used by 44% of open
      angle glaucoma patients at time of referral. CONCLUSION: The clinical follow-up
      of glaucoma patients and glaucoma suspects should primarily take place at an
      ophthalmologist's office and the new effective glaucoma drugs and laser
      treatments should also be more actively in use. The cooperation between the
      referring ophthalmologists and the university clinic should be improved.
      Hospitalisation turned out to be unnecessary because, with a few exceptions, all
      procedures could have been performed on an out-patient basis, which is a general
      practice in most glaucoma clinics today. The university clinic should focus only
      on those patients who need special evaluation or surgical treatment.

PMID- 9527334
TI  - Silicone oil removal: results, risks and complications.
AB  - PURPOSE: We studied the results and complications of silicone oil removal
      applying basic criteria for the selection of eyes. METHODS: The criteria for oil
      removal: 1. Completely attached retina for at least 4 weeks, 2. Absence of
      tractions and active proliferations, 3. Preoperative vision > 0.01. The oil was
      removed from 90 of 261 oil filled eyes (removal rate: 34.5%). 83 eyes were
      included in the further study. FOLLOW-UP: 1.3-62.5 months (mean 15.7). RESULTS:
      Visual acuity improved (> or = 1 line) in 40 of the 83 eyes (48.2%), remained
      unchanged in 22 eyes (26.5%) and deteriorated (> or = 1 line) in 21 eyes (25.3%).
      COMPLICATIONS: reproliferations (42.2%), retinal detachment (20.5%), pressure
      rises (27.7%), lens opacification (36.7%), severe keratopathy (8.4%). CONCLUSION:
      Silicone oil removal has a distinct rate of complications, despite preoperative
      selection of eyes with a better prognosis. Reduction of reproliferations and
      weighing of risk and benefit could improve the results.

PMID- 9527335
TI  - Management of ocular hypertension and open angle glaucoma: clinical practice and
      computer-assisted decision-making.
AB  - PURPOSE: To evaluate the feasibility of computerized decision support in the
      management of patients with open angle glaucoma or ocular hypertension. METHOD:
      Based on a Swedish consensus document a computer program was developed, which
      provided one of 25 different recommendations for appropriate action. In 373
      patient visits to seven different eye clinics, the program's recommendations were
      compared to the actual decisions made by the responsible ophthalmologists.
      RESULTS: Notable differences were observed between the clinics' management
      strategies, especially regarding follow-up frequency and start or increase of
      anti-glaucoma treatment. The program's recommendations conformed with the
      clinical decisions in 23 to 92% of the cases when a standard management strategy
      was simulated. The concordance increased to 93 to 100%, when policy differences
      between the clinics were taken into account. CONCLUSION: Clinical decision-making
      in the management of patients with ocular hypertension or open angle glaucoma can
      be implemented in a computer program. The optimum management protocol remains to
      be defined.

PMID- 9527336
TI  - Phacoemulsification trabeculectomy compared to other methods of combined cataract
      and glaucoma surgery.
AB  - PURPOSE: To compare three methods of combined cataract extraction and glaucoma
      surgery. METHODS: Retrospective review of 35 eyes of patients who had
      extracapsular cataract extraction and trabeculectomy using a corneoscleral
      incision (SAME), 54 eyes undergoing extracapsular cataract extraction and
      trabeculectomy using a separated corneal incision for cataract extraction and 43
      eyes undergoing phacoemulsification and trabeculectomy. RESULTS: Ninety-one
      percent of the eyes in the SAME group, 85% of the SEPARATE group and 97% of the
      phacoemulsification and trabeculectomy group had an IOP < 22 mmHg at 6 months
      with or without medication (NS). Postoperative visual acuity and astigmatism were
      not significantly different between the groups. The number of eyes requiring YAG
      laser capsulotomy was significantly greater in the extracapsular cataract
      extraction and trabeculectomy (same and separated incision) as compared to the
      phacoemulsification and trabeculectomy group (P < 0.001). CONCLUSION:
      Phacoemulsification and trabeculectomy was not significantly more successful than
      the other methods of combined surgery. Although complication rates were similar,
      visual rehabilitation was faster and there was a reduced incidence of early
      posterior capsule opacification.

PMID- 9527337
TI  - Nd:YAG laser removal of pupillary membranes developed after ECCE with PC-IOL
      implantation.
AB  - PURPOSE: To define the frequency of development of pupillary membranes after ECCE
      with PC-IOL implantation, and to remove the pupillary membranes using the Nd:YAG
      laser. METHODS: From 400 patients who had undergone ECCE and were free from local
      or systemic illness affecting the blood-ocular barrier, 20 eyes developed
      pupillary membranes Nd:YAG laser was used to remove these pupillary membranes.
      RESULTS: The frequency of pupillary membranes was found to be 5% (9.8% in pex
      eyes and 3.3% to the non-pex eyes). Visual acuity improved in 17 eyes by 2 to 5
      Snellen lines. No serious complications were observed, endothelium inclusive.
      CONCLUSION: Pseudoexfoliation might play a significant role in the development of
      postoperative pupillary membranes which could be successfully treated with the
      use of Nd:YAG laser. The safety of the procedure has to be evaluated in relation
      to the corneal endothelium damage in long-term.

PMID- 9527338
TI  - The etiology of uveitis: the role of infections with special reference to Lyme
      borreliosis.
AB  - PURPOSE: To assess the distribution of different uveitis entities and to evaluate
      their associations with infections, especially Lyme borreliosis. METHODS: During
      a one-year period 160 consecutive uveitis patients were evaluated in a university
      clinic. Selected tests were performed depending on the medical history of the
      patient and the clinical picture of the ocular inflammation. RESULTS: Uveitis was
      classified into selected entities for 74.4% of the patients. A direct infection
      was suggested to be linked with uveitis in 23 patients (14.4%). Lyme borreliosis,
      toxoplasmosis, and herpetic infections were the most frequently seen, in seven
      patients (4.3%) each. All patients with Lyme uveitis had manifestations of the
      posterior segment of the eye, such as vitritis, retinal vasculitis,
      neuroretinitis, chorioretinitis, or optic neuropathy. CONCLUSION: Infections are
      an important cause of uveitis in a university clinic. Lyme borreliosis is a newly
      recognised uveitis entity which should be kept in mind in the differential
      diagnosis of intermediate or posterior uveitis in areas endemic for Lyme
      borreliosis.

PMID- 9527339
TI  - Interferon alpha for ocular Behcet's disease.
AB  - PURPOSE: To investigate the therapeutic role of interferon alpha in ocular
      Behcet's disease. METHODS: Three patients with B- or C-hepatitis and ocular sight
      threatening Behcet's disease unresponsive to steroids were treated subcutaneously
      with interferon alpha 3 x 10(6)/unit three times per week for a mean period of 22
      months (range: 12-31 months). The course of ocular and systemic lesions was
      recorded and compared with a similar pre-treatment period. RESULTS: At least a
      50% reduction in the number of ocular relapses was observed in all the patients
      (mean relapse/month: 0.41 versus 0.16 in the pre- and in-treatment period,
      respectively) while during therapy also each relapse lasted less in all subjects.
      A reduction of steroid dependence was observed in all patients, while no
      significant side-effects were related to interferon alpha administration. Two
      patients who tried to stop interferon alpha therapy showed after a mean period of
      12.5 days a recurrence of diffuse uveitis and, one of them experienced oral and
      genital aphthae as well. CONCLUSION: In patients with Behcet's disease interferon
      alpha seems to be a useful alternative therapy for sight-threatening ocular
      involvement.

PMID- 9527340
TI  - Myopia among the Inuit population of East Greenland. Longitudinal Study 1950
      1994.
AB  - PURPOSE: To follow the refraction values in an indigenous population group over
      the course of the past 50 years. METHOD: Case records from a population
      investigation carried out in Ammasalik, East Greeland, by Erik Skeller in 1950
      were studied initially, a total of 1123 eyes were examined by sciascopy and 244
      eyes could be followed sufficiently until about 1990-94. RESULT: The mean
      refraction was initially +0.08 D, while at the last examination the mean had
      increased to +0.69 D. Initially, there was no myopia, defined as at least -1.5 D,
      and at follow-up it was a maximum of 1%, and presumably due to immature cataract.
      A tendency to myopia (< -1.5 D) was found initially in 36%, but in only 22% at
      follow-up. CONCLUSION: The myopinizing factor in East Greenland has not affected
      persons born prior to 1942, even if they had a tendency to myopia (< -1.5 D).

PMID- 9527341
TI  - Epidemiology of pseudoexfoliation in the island of Crete (Greece).
AB  - PURPOSE: To evaluate the pseudoexfoliation (PEX) prevalence in the island of
      Crete (Greece). METHOD: Organized visits to various villages, to examine a
      predetermined number of people born and living in these villages, in
      collaboration with the local birth register offices. RESULTS: PEX prevalence in
      Crete, in people aged 40 years and more, was found to be 16.1% (men: 21.3%,
      women: 12.6% - Prefecture of: Heraklion 11.5%, Chania 13.4%, Lasithi 16.9%,
      Rethymnon 27%). 28.8% of PEX-patients presented IOP > 21 mmHg. In unilateral PEX
      patients, mean IOP of PEX-eyes was found to be 17.82 mmHg versus 15.6 mmHg in
      fellow eyes. CONCLUSION: PEX prevalence was higher in men than in women and
      increases with age, as does bilaterality. A correlation between increased PEX
      prevalence and high altitude may exist. PEX is a risk factor for the development
      of IOP disturbances which seem to appear earlier in women.

PMID- 9527342
TI  - Retinoblastoma which developed in microphthalmia.
AB  - We report a rare case of retinoblastoma which developed in unilateral
      microphthalmia. A 4-year-old girl presented with a large, intraocular mass in
      microphthalmia without a family history of retinoblastoma. The eyeball was
      enucleated due to rapid growth of the intraocular tumor. Microscopically it
      proved to be a retinoblastoma with some Flexner-Wintersteiner rosettes. This
      unusual case shows that retinoblastoma should not be excluded just because the
      eye is small, particularly if the family history is not available or is
      incomplete.

PMID- 9527343
TI  - Acute glaucoma and acute corneal oedema in association with tularemia.
AB  - PURPOSE: To describe the clinical course of oculoglandular tularemia with acute
      glaucoma and corneal oedema. METHODS: Clinical course, results of laboratory
      assays and treatment of oculoglandular tularemia in a 58-year-old woman. RESULTS:
      The patient had acute glaucoma and corneal oedema in connection with acute
      tularemia. At the onset of the disease she had a fever (39 degrees C), pains in
      her muscles and in her right eye. The intraocular pressure, which was 68 mmHg at
      the beginning was lowered with intravenous and per oral acetatcolamide together
      with timolol and pilocarpine eyedrops, and because of a narrow anterior chamber,
      with subsequent laser iridotomies. The tularemia was treated with ciprofloxacin
      500 mg twice daily for ten days. Vision was finger counting at the beginning of
      the disease. The corneal oedema gradually subsided and vision normalized during
      the two-month follow-up. CONCLUSION: Oculoglandular tularemia was connected with
      acute glaucoma and corneal oedema.

PMID- 9527344
TI  - Antinutritional factors in anasazi and other pinto beans (Phaseolus vulgaris L.).
AB  - Antinutritional factors of anasazi bean were compared to traditional pinto bean
      (Phaseolus vulgaris L.). Anasazi beans contained less (p<0.001) soluble and bound
      condensed tannins compared to pinto beans. No differences (p>0.05) in stachyose
      and raffinose content were found between the two bean types; verbascose was not
      detected at all. Significant (p<0.05) differences in lectin content were observed
      between anasazi and pinto bean. The lectins of anasazi beans were classified as
      non toxic and those of the pinto beans as toxic types. No differences (p>0.05) in
      inhibitor activity against human and bovine trypsin and chymotrypsin were found
      between the two bean types.

PMID- 9527345
TI  - Nutritional and toxic factors in selected wild edible plants.
AB  - Nutritional (ascorbic acid, dehydroascorbic acid and carotenes); antinutritional
      and toxic components (oxalic acid, nitrate and erucic acid) were determined in
      sixteen popular species of wild edible plants which are collected for human
      consumption in southeast Spain. Ascorbic + dehydroascorbic acids contents were
      very high in several species, especially in Chenopodium album L. (155 mg/100 g).
      Carotenoid content ranged from 4.2 mg/100 g (Stellaria media Villars) to 15.4
      mg/100 g (Amaranthus viridis L.). A range of values was found for oxalic acid
      from absence to 1100 mg/100 g of plant material. Nitrate contents ranged from 47
      mg/100 g (Salicornia europaea L.) to 597 mg/100 g (Amaranthus viridis L.). Low
      amounts of erucic acid were found in the Cruciferae family (Sisymbrium irio L.
      1.73%; Cardaria draba L. 1.23%) and Plantago major L. 3.45%.

PMID- 9527346
TI  - Structural characteristics of corn starches extruded with soy protein isolate or
      wheat gluten.
AB  - Commercially available corn starches containing 0, 25, 50 and 70% amylose were
      extruded with 10, 20 and 30% soy protein isolate (SPI) or wheat gluten (WG) at
      22% moisture content (dry basis) in a C.W. Brabender single screw laboratory
      extruder using a 140 degrees C barrel temperature and a 140 rpm screw speed.
      True, solid and bulk densities; percent total, closed and open pores; and shear
      strengths of the extrudates were determined. The microstructures of the
      extrudates were studied by scanning electron microscopy (SEM). The total pores of
      the extrudates were affected significantly (p > F = 0.0001) by type of protein
      (SPI or WG) and starch amylose. The open or closed pores, were affected by
      protein type only. The interaction between amylose and protein contents was
      highly significant (p > F = 0.0001). In general, the total pores and bulk
      densities were higher for WG-starch extrudates compared to SPI-starch extrudates.
      These values decreased as amylose content increased from 0 to 25% and then
      increased thereafter. The open pores, on the other hand, increased with
      increasing protein content from 10 to 20% and then decreased. Extrudates
      containing WG had higher shear strengths than those containing SPI.

PMID- 9527347
TI  - Date bars fortified with almonds, sesame seeds, oat flakes and skim milk powder.
AB  - Fortified date bars were prepared from some of the commonly grown date cultivars
      in the United Arab Emirates. The average ash, fat and protein contents in the
      control date bar sample were 1.78, 6.09 and 7.83%, respectively. The ash and
      protein contents increased, but the fat content decreased slightly with the
      inclusion of skim milk powder in the remaining date bar formulations. All the
      date bar samples were found to be free from Enterobacteriaceae and coliforms.
      Date fruit, which usually supplies only calories, can thus be turned into a
      product having significant amounts of other valuable nutrients.

PMID- 9527348
TI  - Effects of Rhizobium inoculation, organic and chemical fertilizers on yield and
      physical properties of faba bean seeds.
AB  - A field experiment was carried out to investigate the effect of Rhizobium
      inoculation, sulphur, nitrogen and chicken manure on yield, 100-seed weight,
      cookability, non-soakers, total defects and hydration coefficient of faba bean.
      The results showed that sulphur, nitrogen and chicken manure treatments
      significantly (p < or = 0.05) increased yield, 100-seed weight, non-soakers, and
      hydration coefficient, in the absence of Rhizobium inoculation. The results also
      showed that Rhizobium inoculation significantly (p < or = 0.05) increased yield,
      100-seed weight, cookability, but decreased non-soakers. A positive correlation
      (r = 0.90) was observed between the non-soaker percent and the total defect
      percent. No correlation was found between non-soakers, hydration coefficient and
      cookability. The results of this investigation indicate that Rhizobium
      inoculation is a promising fertilizer because it is cheap, easy to handle and
      improves plant growth and seed quality. The efficiency of inoculation could be
      improved with the addition of biological, chemical or organic fertilizers.
      Generally, fertilization of faba bean with nitrogen, sulphur or chicken manure
      not only increased plant growth and yield, but also improved seed quality and
      nutritional value.

PMID- 9527349
TI  - An evaluation of the microflora associated with fermented African oil bean
      (Pentaclethra macrophylla Bentham) seeds during ugba production.
AB  - The microorganisms associated with fermented African oil bean (Pentaclethra
      macrophylla Bentham) seed during ugba production was studied. Only bacteria were
      isolated from the ugba samples used. Although the bacteria included Bacillus
      spp., Lactobacillus spp., Staphylococcus spp., Micrococcus spp. and members of
      the family Enterobacteriaceae, only the Bacillus spp. were found to ferment
      African oil bean seeds to ugba. Bacillus spp. were the predominant microorganisms
      present, constituting over 95% of the total microbial population density. An
      increase in the number of Bacillus cells of about 2 log units daily, which
      attained a maximum density of log10 9.00 - log10 11.90 cfu/g after 3 days was
      observed. Contrarily, the Lactobacillus spp. increased minimally and attained a
      maximum value of log10 4.20 - log10 6.35 cfu/g within the same period. The
      Staphylococcus spp., Micrococcus spp. and the members of the family
      Enterobacteriaceae remained fairly steady in number for 24h, increased slightly
      till the 3rd day followed by exponential increases which attained maximum values
      of between log10 9.20 - log10 11.00, about the 7th day. Bacillus spp. cells also
      had the highest protease activities which were significantly (p < 0.05) higher
      than the values for the other bacterial isolates. The Bacillus spp. responsible
      for the fermentation of African oil bean seeds to ugba were identified as
      Bacillus coagulans, B. macerans, B. megaterium, B. pumilis and B. subtilis.

PMID- 9527350
TI  - Thermoxidized palm oil induces reproductive toxicity in healthy and malnourished
      rats.
AB  - Repeatedly thermoxidized palm oil (TPO), simulating local culinary practice, was
      fed for eight weeks at 15% of a balanced basal diet to two sets of male and
      female weanling albino rats of Wistar strain. The first set of animals were
      normal and healthy while the second set were kwashiorkoric. Primary controls (PC)
      of all rats were fed a balanced basal diet of commercial rat pellets while
      secondary controls (SC) were fed the balanced basal diet supplemented with 15%
      untreated palm oil. The findings indicate that fertility, as expressed by the
      pregnancy rate of healthy test rats, was 78% when compared with 80% in PC (p <
      0.05). Fetotoxicity was additionally observed in that neonatal birth weights and
      litter size in test rats (4.92 g and 6.70, respectively) were inferior (p < 0.05)
      to both SC and PC (4.96 g and 8.40; 5.38 g and 9.25, respectively). Protein
      energy malnutrition worsened the observed TPO-induced reproductive toxicities in
      that reproductive capacities of the rehabilitated animals were inferior to that
      of the healthy animals. Pregnancy rates in test animals were reduced by as much
      as 55% (p < 0.01) while fetotoxicities were also more pronounced (p < 0.05).

PMID- 9527351
TI  - Hypolipidemic effect of coriander seeds (Coriandrum sativum): mechanism of
      action.
AB  - The effect of the administration of coriander seeds (Coriandrum sativum) on the
      metabolism of lipids was studied in rats fed a high fat diet with added
      cholesterol. The spice had a significant hypolipidemic action. The levels of
      total cholesterol and triglycerides decreased significantly in the tissues of the
      animals of the experimental group which received coriander seeds. Significant
      increases in beta-hydroxy, beta-methyl glutaryl CoA reductase and plasma lecithin
      cholesterol acyl transferase activity were noted in the experimental group. The
      level of LDL + VLDL cholesterol decreased while that of HDL cholesterol increased
      in the experimental group compared to the control group. The increased activity
      of plasma LCAT, enhanced hepatic bile acid synthesis and the increased
      degradation of cholesterol to fecal bile acids and neutral sterols appeared to
      account for its hypocholesterolemic effect.

PMID- 9527352
TI  - On the pitfalls of journal ranking by Impact Factor.

PMID- 9527353
TI  - Biological factors contributing to failures of osseointegrated oral implants.
      (I). Success criteria and epidemiology.
AB  - The aim of this review was to offer a critical evaluation of the literature and
      to provide the clinician with scientifically-based diagnostic criteria for
      monitoring the implant condition. The review presents the current opinions on
      definitions of osseointegration and implant failure. Further, distinctions
      between failed and failing implants are discussed together with the presently
      used parameters to assess the implant status. Radiographic examinations together
      with implant mobility tests seem to be the most reliable parameters in the
      assessment of the prognosis for osseointegrated implants. On the basis of 73
      published articles, the rates of early and late failures of Branemark implants,
      used in various anatomical locations and clinical situations, were analyzed using
      a metanalytic approach. Biologically related implant failures calculated on a
      sample of 2,812 implants were relatively rare: 7.7% over a 5-year period (bone
      graft excluded). The predictability of implant treatment was remarkable,
      particularly for partially edentulous patients, who showed failure rates about
      half those of totally edentulous subjects. Our analysis also confirmed (for both
      early and late failures) the general trend of maxillas, having almost 3 times
      more implant losses than mandibles, with the exception of the partially
      edentulous situation which displayed similar failure rates both in upper and
      lower jaws. Surgical trauma together with anatomical conditions are believed to
      be the most important etiological factors for early implant losses (3.60% of
      16,935 implants). The low prevalence of failures attributable to peri-implantitis
      found in the literature together with the fact that, in general, partially
      edentulous patients have less resorbed jaws, speak in favour of jaw volume, bone
      quality, and overload as the three major determinants for late implant failures
      in the Branemark system. Conversely, the ITI system seemed to be characterized by
      a higher prevalence of losses due to peri-implantitis. These differences may be
      attributed to the different implant designs and surface characteristics. On the
      basis of the published literature, there appears to be a number of scientific
      issues which are yet not fully understood. Therefore, it is concluded that
      further clinical follow-up and retrieval studies are required in order to achieve
      a better understanding of the mechanisms for failure of osseointegrated implants.

PMID- 9527354
TI  - A metabolism study of human masseter muscle by 31P magnetic resonance
      spectroscopy during long periods of exercise and recovery.
AB  - The metabolism of the human masseter muscle was investigated using phosphorus
      (31p) magnetic resonance spectroscopy (MRS) during long periods of exercise and
      recovery. Eleven subjects aged 19 to 28 yr were examined by 31p MRS during four
      consecutive periods of 13 min each: rest, exercise, recovery 1 and 2. For each
      subject, a biting force equal to 20% of maximum voluntary biting force was
      applied and controlled during the exercise period to produce maximum fatigue. 31p
      MR spectra were localized from a 24 cm3 volume of interest using an image
      selected in vivo spectroscopy (ISIS) sequence and a 6 cm diameter surface coil
      placed on the left masseter. Compared to the resting level, the phosphocreatine
      (PCr) content decreased by 26% during exercise, while the inorganic phosphate
      (Pi) concentration increased by 65%. During the two recovery periods, the Pi
      content remained decreased compared with the resting level by 36% and 30%,
      respectively. The Pi/PCr ratio was increased from 0.30+/-0.04 at rest to 0.63+/
      0.13 during exercise while the adenosine triphosphate (ATP)/Pi ratio was
      decreased. The pH decreased from 7.02+/-0.03 to 6.93+/-0.04 during exercise and
      returned to control level (7.09+/-0.08) only during the second recovery period.
      These results suggest that the masseter muscle is characterized by high ATP
      turnover and, therefore, high oxidative phosphorylative activity in agreement
      with its constitution of predominantly fatigue resistant type I fibers.

PMID- 9527355
TI  - Interleukin-1beta in plasma and synovial fluid in relation to radiographic
      changes in arthritic temporomandibular joints.
AB  - The aim of this study was to investigate the level of the cytokine IL-1beta in
      plasma and temporomandibular joint (TMJ) synovial fluid of patients with
      arthropathies, and to study the relation between IL-1beta levels of synovial
      fluid and plasma as well as radiographic changes of the TMJ. 31 patients with
      general disease, 14 with rheumatoid arthritis (RA) and 17 with various
      arthritides were included in the study. Synovial fluid and blood samples were
      collected, and an individualized tomography of the TMJ was performed. Detectable
      levels of IL-1beta were found in 5 out of 39 synovial fluids and in 10 out of 27
      plasma samples. The presence of IL-1beta in both plasma and synovial fluid was
      more frequent in RA patients than in the non-RA group. The extension of
      radiographic erosion was significantly greater in joints with IL-1beta than in
      those without. Both the extension of erosion and grade of radiographic changes of
      the TMJ were greater in patients with detectable IL-1beta level of plasma than in
      patients without. Our study indicates that presence of IL-1beta in plasma and
      synovial fluid is related to radiographic changes of the TMJ.

PMID- 9527356
TI  - Fluoride concentration in the approximal area after using toothpicks and other
      fluoride-containing products.
AB  - The aim of this work was to study the fluoride (F) concentration in the
      approximal area after using toothpicks and other F-containing products. The
      exposure time was standardised to 2 min. 24 subjects participated, divided into 4
      groups, with 6 individuals per group. In 3 of the groups, the following 4
      products were compared: (1) a toothpick impregnated in 4% NaF; (2) a dentifrice
      containing 0.32% NaF; (3) a mouthrinse solution containing 0.025% NaF; (4) a
      tablet containing 0.55 mg NaF. In the 4th group, 3 commercial F toothpicks and 2
      F dental flosses were compared. In all 4 groups, the F concentration was
      determined up to 60 min at 4 approximal sites. On each sampling occasion, 3
      triangle-shaped paper points were used, absorbing 3 x 1 microl. In general, the
      toothpick gave similar or somewhat higher F concentrations in the approximal area
      than the dentifrice, mouthrinse solution and tablet. Comparing the various
      commercial toothpicks and dental flosses, 2 of the toothpicks gave higher
      approximal F concentrations than the other 3 products. When comparing the series
      in which the very first sample was collected from 2-20 min after the F treatment,
      it was found that the sampling procedure itself reduced the subsequent approximal
      F concentration. The main conclusion from this study is that an F-impregnated
      toothpick is a promising vehicle for delivery of fluoride to the approximal area.

PMID- 9527357
TI  - Effect of a chlorhexidine/thymol-containing varnish on prostaglandin E2 levels in
      gingival crevicular fluid.
AB  - The aim was to study the effect of a chlorhexidine/thymol-containing varnish
      (Cervitec) on the levels of prostaglandin E2 (PGE2) in gingival crevicular fluid
      (GCF). The material consisted of 25 adolescents and young adults with fixed
      orthodontic appliances exhibiting gingival inflammation. Four buccal sites,
      adjacent to bands and brackets, were selected on each patient and randomly
      treated with either a varnish containing chlorhexidine diacetate (1% w/w) and
      thymol (1% w/w) or a placebo varnish without active ingredients. After baseline
      registration, the varnishes were applied twice within 3 d. Follow-up examinations
      were performed after 3, 8 and 30 d. The gingival inflammation was assessed by
      bleeding on probing, volume of GCF with a Periotron 8000 and PGE2 level in GCF by
      using a radioimmuno assay. Compared with baseline, a statistically significant
      reduction in the volume of GCF was recorded at the chlorhexidine/thymol treated
      sites in contrast to the placebo. The mean PGE2 levels were significantly reduced
      after the test varnish treatment compared with baseline and differed
      significantly from placebo after 8 d. The findings suggest that treatments with
      the antibacterial varnish result in reduced gingival inflammation and may thus be
      beneficial for patients with fixed orthodontic appliances.

PMID- 9527358
TI  - LPS from Actinobacillus actinomycetemcomitans and production of nitric oxide in
      murine macrophages J774.
AB  - Nitric oxide (NO) plays a complex role in the modulation of the inflammatory
      response, having either a pro-inflammatory or a protective role. Actinobacillus
      actinomycetemcomitans is considered an important etiological agent in localized
      juvenile periodontitis. We have studied the effect of lipopolysaccharide (LPS)
      extracted from this periodontopathogenic bacterium on NO synthesis in an in vitro
      murine macrophage system. LPS from A. actinomycetemcomitans induced a significant
      production of NO even at concentrations as low as 1 ng/ml, whereas LPS from E.
      coli had to be added in concentrations of 100 ng/ml to obtain similar effects.
      Production of NO was blocked by NG-nitro-L-arginine methylester, and pre
      treatment of LPS from A. actinomycetemcomitans with polymyxin B abolished the
      production of NO, while prostaglandin E2 enhanced the synthesis of NO.

PMID- 9527359
TI  - Mercury content in amalgam tattoos of human oral mucosa and its relation to local
      tissue reactions.
AB  - Mucosal biopsies from 48 patients with and 9 without amalgam tattoos were
      analysed with respect to their mercury content, distribution of mercury in the
      tissue, and histological tissue reactions. The distribution of mercury was
      assessed by autometallography (AMG), a silver amplification technique. The
      mercury content was determined by energy dispersive X-ray fluorescence (EDXRF), a
      multielemental analysis. Mercury was observed in connective tissue where it was
      confined to fibroblasts and macrophages, in vessel walls and in structures with
      the histological character of nerve fibres. A correlation was found between the
      histopathological tissue reaction, the type of mercury deposition, the intensity
      of the AMG reaction, and the mercury content. Mercury was also found in patients
      with amalgam dental fillings but without amalgam tattoos.

PMID- 9527360
TI  - Effect of polymerization temperature and time on the residual monomer content of
      denture base polymers.
AB  - The aim of this study was to investigate the effect of polymerization time and
      polymerization temperature on the residual methyl methacrylate (MMA) content of
      two heat-cured and two autopolymerized denture base polymers. Gas chromatography
      was used to determine the residual MMA content of three test specimens of each
      type of polymer. Increasing the polymerization temperature for the
      autopolymerized denture base resins from 30 degrees C to 60 degrees C decreased
      the residual MMA content of the polymer from an average of 4.6 wt% to 3.3 wt%.
      With the heat-cured denture base resins, a curing cycle at a polymerization
      temperature of 70 degrees C followed by a period at 100 degrees C significantly
      reduced the residual monomer content of the polymer when compared with a resin
      cured at 70 degrees C only. Polymerizing the heat-cured denture base resin at 100
      degrees C only for various lengths of time significantly affected the residual
      MMA content of the polymer. The lowest residual MMA content (0.07 wt%) was
      obtained by polymerizing the heat-cured denture base resin at 100 degrees C for
      12 h. The results of this study suggest that the polymerization temperature and
      polymerization time considerably affect the residual MMA content of denture base
      polymers.

PMID- 9527361
TI  - Bond strength of Bis-GMA and glass ionomer pit and fissure sealants using cyclic
      fatigue.
AB  - The aim of the study was to determine the bond strength of glass ionomer and
      resin-modified glass ionomer sealants compared to Bis-GMA sealants using both
      static and cyclic fatigue shear testing. Four materials were evaluated: D, a Bis
      GMA sealant with 10% phosphoric acid etchant; FC, a resin-modified glass ionomer
      sealant with 20% polyacrylic acid etchant; FD, a resin-modified glass ionomer
      sealant with 10% polyacrylic acid etchant; and FSC, a self-cured glass ionomer
      sealant with no etchant. Gelatin capsules filled with the sealant material were
      bonded to the enamel surfaces of bovine teeth after appropriate surface
      conditioning and then tested in shear static and cyclic fatigue. Static and
      cyclic shear bond strengths, respectively, for each group were (MPa): FC: 21.1+/
      2.8 and 17.1+/-3.1; FD: 14.6+/-5.9 and 8.5+/-3.1; D: 10.8+/-4.9 and 4.7+/-2.6;
      FSC: 8.7 (1.0 and 2.9+/-0.6. The resin-modified glass ionomer sealants had better
      fatigue bond strength than both Bis-GMA and self-cured glass ionomer sealants
      with the surface conditioning affecting the bond strength of the resin-modified
      glass ionomer sealants.

PMID- 9527363
TI  - "Smokeless (Spit) Tobacco: a Review of the State of the Science." Proceedings of
      a Symposium during the 74th General Session of the International Association for
      Dental Research. San Francisco, California, March 13, 1996.

PMID- 9527364
TI  - Index-busting.

PMID- 9527365
TI  - 8th International Magnesium Symposium. Heraklion, Greece, 5-9 October 1997.
      Abstracts.

PMID- 9527362
TI  - Mercury vapor release from dental amalgam after laser treatment.
AB  - The aim of this in vitro study was to determine whether the treatment of amalgam
      with different lasers leads to an increased release of mercury (Hg) vapor. In the
      case of CO2-lasers in pulse and continuous-wave mode, there was no effect visible
      on the amalgam surface and no Hg vapor could be detected. Using an Nd:YAG, Er:YAG
      or Nd:YLF laser, crater formation could be observed on the amalgam surfaces. With
      the solid state lasers tested, however, the Hg vapor measurements taken indicated
      that pulses applied to amalgam cause a substantially increased release of Hg
      vapor. This vapor may contribute to the patient's total mercury exposure.

PMID- 9527366
TI  - [Cardial Magnetic Resonance Workshop. Bad Nauheim, October 31-November 1, 1997.
      Abstracts].

PMID- 9527367
TI  - [Urinary infection and pregnancy: a public health problem?].

PMID- 9527368
TI  - [Meningococcal meningitis:descriptive study of 76 cases in a pediatric hospital].
AB  - BACKGROUND: One of the principal causes of bacterial meningitis (BM) in children
      older than one month is Neisseria meningitidis (Nm). A quick diagnosis and an
      immediate treatment are considered essential for a good outcome. We propose this
      study with the purpose of evaluating the clinical and epidemiological
      characteristics of the patients with BM caused by Nm and analyzing the effect on
      the presentation and incidence of sequelae and/or complications of the time
      elapsed since the starting of symptoms and the beginning of the treatment.
      METHODS: We performed a retrospective analysis of the clinical registers of 76
      patients diagnosed as BM caused by Nm entered in the Hospital de Pediatria Pedro
      de Elizalde, Buenos Aires, Argentina, during the years 1992 and 1993. We
      investigated age, sex, date of entrance, first symptoms, biochemistry of
      cerebrospinal fluid (CSF), nutritional status, convulsions and/or complications,
      length of internation and conditions at discharge. Processing was done with Epi
      info 5.0. Differences between qualitative variables were analyzed with chi 2 and
      differences between means with z-test. RESULTS: Boys were majority; fever was the
      most frequent initial symptom; petechiae were less frequently found, specially
      among infants. 79% of the patients had CSF of purulent characteristics; 32.9% of
      the patients had complications during their evolution; its incidence raised up to
      48% in infants. Lethality was 1.3%, 6.5% of the children had sequelae at the
      moment of discharge. The average time of internment was 13 days. There were no
      significant differences when different groups were compared according to their
      prior evolution time. CONCLUSIONS: 1) Petechiae and vomits were significantly
      less frequent in infants; 2) the incidence of complications was significantly
      higher in this last group; 3) no greater incidence of complications or sequelae
      was observed in patients whose previous period of evolution was longer than 48
      hours; 4) in all groups of age we found insidious forms of starting, and 5) there
      were patients with CSF of normal biochemical characteristics in all groups
      considered independently of the time of evolution elapsed.

PMID- 9527370
TI  - [Acute epiglottitis caused by Haemophilus influenzae type b in children:
      presentation of 21 cases].
AB  - BACKGROUND: The aim of this paper is to review the epidemiological, clinical and
      therapeutical characteristics of Haemophilus influenzae type b (Hib) epiglottitis
      in children at a time when an efficient and safe vaccination is available.
      METHODS: The clinical histories of 21 children admitted to Children's Hospital La
      Fe (1971-1996) with a clinical diagnosis of epiglottitis and isolation of the
      microorganism in blood cultures (20 cases) and surface culture of the epiglotis
      (one case) are reviewed. RESULTS: The annual average was 4/100,000 children under
      5 years of age. Evolution prior to diagnosis was > 12 hours in 52.4% of the
      cases. More males were affected (52.4% vs 47.6%). All the children except one
      (95.2%) were under 5 years of age; 81% were under 3 years of age and 1 child was
      6 years and 8 months old. Respiratory distress (100%) and fever > or = 38 degrees
      C (85.7%) were the most common clinical manifestations. General health was
      affected in 71.4% of the cases and 66.7% had leucocytosis on admission. The
      clinical diagnosis was confirmed by direct visualization of the epiglotis in
      76.1% of the cases. Hib was isolated in blood culture in 20 cases (95.2%). The
      strains produced beta-lactamases and were ampicillin-resistant in 57.1%. 19
      children (90.5%) required endotracheal intubation. Initial empiric antibiotic
      therapy was third generation cephalosporins (cefotaxime or ceftriaxone) alone or
      combined with ampicillin. One child died (4.8%). CONCLUSIONS: Pediatricians must
      still be aware of this serious infection in order to diagnosis and treat it as
      early as possible.

PMID- 9527369
TI  - [Species identification of intestinal microsporidiosis in HIV-positive patients
      using the polymerase chain reaction].
AB  - BACKGROUND: Microsporidia are opportunistic parasites which, due to their
      morphologic characteristics, continue presenting diagnostic problems. Species
      specific identification of microsporidia has become important because of varying
      levels of response to albendazole, which is the only effective treatment for some
      kinds of intestinal microsporidiosis. Although these parasites cause up to 50% of
      otherwise unexplained chronic diarrhea in HIV-positive patients, the number of
      reported cases is still very scarce in our country when compared to the existing
      HIV-positive population. METHODS: Intestinal microsporidiosis in HIV-positive
      patients with diarrhea was investigated using the modified trichrome staining
      technique. Microsporidia species identification was done by indirect
      immunofluorescence (IIF) and polymerase chain reaction (PCR) with specific
      primers. RESULTS: Six new cases of intestinal microsporidiosis caused by
      Enterocytozoon bieneusi were diagnosed in Madrid (Spain). All patients were in an
      advanced state of the HIV infection and they presented CD4+ values equal or
      inferior to 100 x 10(6)/I. CONCLUSIONS: Due to the number of cases that are
      accumulating, microsporidia must be included among the enteropathogens
      responsible for chronic diarrhea in HIV-positive individuals in Spain. The PCR
      technique using specific primers is a suitable determinator of the microsporidia
      species implicated in this intestinal pathology.

PMID- 9527371
TI  - [Patients with human immunodeficiency virus admitted to the emergency service of
      a general hospital].
AB  - BACKGROUND: The description of the demographic, toxicologic, immunologic and
      clinicopathologic characteristics of patients with known human immunodeficiency
      virus infection (HIV) admitted to hospital through the emergency department is
      presented. METHODS: A cohort study of patients with known HIV seropositivity who
      consecutively attended the emergency department of the Hospital del Mar in
      Barcelona, Spain, from January to March 1995 and who required hospitalization
      with follow up until discharge from hospital was performed. From the clinical
      history of each patient the following parameters were analyzed: age, sex,
      domicile, toxicologic history, risk factors 'for HIV infection, epidemiologic and
      pathologic history, CD4 lymphocyte count, clinical stage, the complementary tests
      carried out, as well as the diagnosis on admission and hospital discharge.
      RESULTS: During the study period, 6,379 patients were attended in the emergency
      department, 323 of whom corresponded to HIV seropositive patients. Of 1,460
      admissions, 126 (77 males [61%] and 49 females [39%]) corresponded to known HIV
      patients, of whom 75.5% were or had been intravenous drug addicts. Eighty-three
      point three percent were from the health care area assigned to the hospital.
      According to the AIDS clinical stage, 26 (20.6%) belonged to group A, 14 (11.1%)
      to group B and 86 (68.2%) to group C. The complementary tests performed were:
      thorax radiography in 80%, abdomen radiography in 4%, cerebral computerized axial
      tomography (CAT) in 9.5%, lumbar punction in 5%, thoracocentesis in 3%,
      paracentesis in 4% and clinical analysis in 95%. The most frequent cause of
      admission was pulmonary disease (40%) with 21.5% corresponding to tuberculosis.
      Homogenesis among diagnoses on admission and discharge was 75%. CONCLUSIONS: The
      high percentage of hospitalary admissions in known HIV patients requiring medical
      attention in the emergency department is of note. The patients are usually from
      the health care area of the center, belong to group C, require a high number of
      complementary tests with pulmonary disease being the most frequent cause of
      admission.

PMID- 9527372
TI  - [In vitro inhibition of the growth of Gardnerella vaginalis by bacteriocins
      produced by strains of Pseudomonas aeruginosa].
AB  - BACKGROUND: Pseudomonas aeruginosa with inhibitory capacity in vitro was studied
      on Gardnerella vaginalis strains. METHODS: Antimicrobial activity was
      demonstrated by inhibitory halos of bacterial growth on solid media by two
      methods: crossed streak and agar well diffusion. The inhibitory activity of this
      substance produced by P. aeruginosa was characterized as bacteriocin by: activity
      spectrum sensitivity proteolytic enzyme, chloroform, heat, pH, ultraviolet,
      irradiation effect and molecular weight. RESULTS: Four strains of P. aeruginosa
      producers of bacteriocins were chosen for this study and contacted with 40
      strains of G. vaginalis. The producing strain D inhibited 70% of these G.
      vaginalis strains. The strains B and C inhibited 55% and 52.5%, respectively. The
      3 strains presented a wide rank of action but the strain A had effect on a few
      strains of G. vaginalis. CONCLUSIONS: This work showed the inhibitory in vitro
      effect of bacteriocins of P. aeruginosa on strains of G. vaginalis. The results
      obtained suggest the probable topic application of bacteriocins as an alternative
      of conventional therapeutic on this infection biological control.

PMID- 9527373
TI  - [Characterization of the resistance to combinations of beta lactams and
      inhibitors of beta-lactamases in Escherichia coli. Effect of the type and amount
      of beta-lactamase production].
AB  - BACKGROUND: The aim of this study was to characterize resistance of Escherichia
      coli in our environment to four associations of beta-lactams and beta-lactamase
      inhibitors (beta Lac) studying the influence of the type and level of beta Lac
      production. METHODS: The minimum inhibitory concentration (MIC) to
      ampicillin/sulbactam (A/S), amoxycillin/clavulanic acid (A/C),
      ticarcillin/clavulanic acid (T/C) and piperacillin/tazobactam (P/T) assessed was
      in 245 strains of E. coli resistant to ampicillin, consecutively isolated in our
      laboratory from September 1995 to March 1996. The beta Lac produced by these
      isolates were identified by isoelectrofocusing and spectrophotometrically
      quantified. RESULTS: The sensitivity to A/S, A/C, T/C and P/T was of 9.4, 86.9,
      64.5 and 89.4%, respectively. The strains with only one beta Lac which cofocused
      with TEM-1 were the most frequent (215/245), followed by those producing a
      cofocusing enzyme with SHV-1 (7/245). A significant correlation was observed
      between beta Lact activity of the 215 TEM-1 strains and their MIC at A/S (r =
      0.53; p < 0.001), A/C (r = 0.46; p < 0.001), T/TC (r = 0.58; p < 0.001), and P/T
      (r = 0.42; p < 0.001). The comparison between enzyme activity of the isolates of
      the different categories of susceptibility showed significant differences (p <
      0.05) for the four associations studied. CONCLUSION: TEM-1 production is the main
      cause of resistance to beta-lactams in E. coli in our environment. The inhibitory
      efficacy of sulbactam, clavulanic acid and tazobactam over TEM-1 is inversely
      proportional to the amounts of enzyme produced. The high rate of resistance to
      A/S and T/C E. coli presents in our environment is mainly due to a
      hyperproduction of TEM-1.

PMID- 9527374
TI  - [Ischemia of the lower limbs as the initial manifestation of Candida albicans
      endocarditis in a parenteral drug addict].
AB  - BACKGROUND: Multiple infective complications have been described in injection
      drug users (IDUs). Infective endocarditis, most frequently caused by Gram
      positive bacteria, with classical features, is one of the most dangerous. In a
      few patients fungi are the cause (less than 5%), and these develop an unusual
      clinical picture. METHODS: An IDUs patient was admitted in our Hospital for
      subacute arterial ischemia at the inferior limbs. A mass inside the abdominal
      aorta was detected by echography and arteriography, which was removed surgically
      a few hours later. RESULTS: The pathologic evaluation of the surgical specimen
      revealed its fungal composition; the culture of this material was characteristic
      of Candida albicans. The clinical suspicion of aortic endocarditis, as the
      emboligenic source responsible of the inferior limbs ischemia, was confirmed with
      the performance of an echocardiography. A few hours after surgery the patient got
      worse; 24 hours later he died due to uncontrolled bleeding of the surgical suture
      in the aorta. CONCLUSIONS: Fungal endocarditis should be thought in IDUs patients
      presenting inferior limbs ischemia. Due to the high mortality of this disease, as
      soon as the diagnosis is suspected, urgent medical and surgical therapy should be
      started.

PMID- 9527375
TI  - [Application of molecular diagnosis to bacteria implicated in upper respiratory
      tract infections].

PMID- 9527376
TI  - [Visualization of motile leaf-like forms using endoscopic retrograde
      cholangiopancreatography].

PMID- 9527377
TI  - [Papulo-nodular lesions of the gluteal region during travel in South America].

PMID- 9527378
TI  - [Diarrhea caused by Cryptosporidium as the initial manifestation of AIDS in an
      elderly man].

PMID- 9527379
TI  - [Persistent bacteremia and infection of an intravascular device by Agrobacterium
      radiobacter (tumefaciens) in a boy with AIDS].

PMID- 9527380
TI  - [Tuberculous abscess simulating complicated acute appendicitis in a patient with
      HIV infection].

PMID- 9527381
TI  - [Dengue, an imported disease underdiagnosed in our environment].

PMID- 9527382
TI  - [Epiglottitis caused by Haemophilus influenzae type b in a patient with AIDS].

PMID- 9527383
TI  - [Thoracic actinomycosis].

PMID- 9527384
TI  - [Meningitis caused by Streptococcus pyogenes in a previously healthy girl].

PMID- 9527385
TI  - [Utility of different analytical techniques in the diagnosis of congenital
      cytomegalovirus infection].

PMID- 9527386
TI  - [The Prague experience].

PMID- 9527387
TI  - [Lung function in workers in a chicken slaughterhouse in the city of Maracaibo,
      Venezuela].
AB  - In order to evaluate the respiratory health status in workers exposed to
      antigenic substances (chicken feathers, serum and dropping), typical of usual
      practice in the avian slaughter-house, pulmonary function was studied on 49
      exposed workers, and in a sample of 49 people with similar anthropometric
      characteristics, non exposed to these substances, by means of occupational
      medical history, spirometric tests, hematologic and biochemical tests, and
      postero-anterior chest x-rays. The values for the spirometric parameters varied
      with sex, age, weight, size, smoking habits, length of employment and exposure
      time, and there were no significant differences between exposed and control
      groups as a whole; showing significant differences with decreasing values for
      CVF, VEF1, PFE, FEF-25% and FEF-50% in the intermediate zone workers, and in
      subjects with short exposure time (< 1 year). Prevalence of clinical findings in
      the exposed population was significantly higher than the non exposed group (p <
      0.001). Laboratory tests showed reduction of monocytes cells in the exposed group
      (p < 0.05) in addition, in the exposed women there was an increase of the
      eosinophiles, total proteins and globulines (p < 0.05). The frequency of
      radiographic findings was significantly higher in the exposed group (p < 0.006),
      and they were no specific. The lack of association between clinical findings,
      laboratory and radiographic findings, with the spirometric results, could be
      explained by the short period of exposure, individual and collectives hygienic
      conditions and size of the sample.

PMID- 9527388
TI  - [Clinico-epidemiologic study of microtia].
AB  - Microtia is a congenital malformation characterized by total or partial absence
      of the whole auricle or any of its components, varying from a small auricle to
      the total absence (anotia). There may be associated atresia of the external
      auditory meatus. The frequency varies in different parts of the world between 0.4
      and 5.5/10,000 newborns. In this paper we report the clinical and epidemiological
      characterization of this congenital malformation in a sample of 97.759 neonates
      born at the Ruiz y Paez Hospital in Ciudad Bolivar, Venezuela, between April 1978
      and December 1994. A total of 38 patients with microtia were identified. The
      global frequency was 3.8 per 10,000/newborns. In 47.4% of the patients microtia
      was an isolated malformation and in 52.6% was associated to other malformations.
      Sixty three percent of the affected were males. The unilateral form was present
      in 81.5% of the cases, more frequently on the right side. The annual frequency of
      the defect was stable over the studied years. The clinical classification of the
      cases with associated malformations allowed us to establish that 18.4% of the
      cases correspond to developmental fields defects, associated to preauricular
      dimples and/or tags, 7.8% were cases of the facio-auriculo-vertebral spectrum and
      in 15.7% the microtia was part of a monogenic or chromosomal syndrome. In 10.5%
      it was not possible to define any etiological or pathogenic mechanism. The
      frequency obtained in this study for microtia shows intermediate values when
      compared with others reports from Latin America.

PMID- 9527389
TI  - [Hypoplasia of the tibia, polydactyly, and triphalangeal thumb: 1st family
      described in Venezuela].
AB  - Werner in 1915, described a patient is characterized by a tibial bilateral
      aplasia or hypoplasia, polydactyly and absent thumbs. Autosomal dominant
      inheritance is demonstrated, with variable expressivity. The objective of this
      work is to describe a child with clinic and radiologic signs of Tibial Hypoplasia
      with Polydactyly. The genealogic study allowed us to suppose that the gene has a
      variable expressivity, since in the maternal branch, malformations such as
      syndactyly of hands, proximal implantation of thumbs and tibiae vara, have been
      found. The clinic, radiologic, and genetic aspects are discussed.

PMID- 9527390
TI  - [Application of electron microscopy and immunohistochemistry to the study of
      malignant tumors: a review of their diagnostic importance].
AB  - The results of examining in the course of the past twenty years a considerable
      number of malignant tumors with transmission electron microscopy and
      immunohistochemistry are discussed. The neoplasms were divided into epithelial
      tumors, tumors of fusiform cells, malignant round cell tumors and tumors of
      endocrine nature. The main ultrastructural findings and the results of
      immunohistochemical studies were pointed out regarding their contributory role in
      the diagnosis as well as for the prognosis and treatment of patients with cancer.

PMID- 9527391
TI  - Cold-induced microtubule disruption and relocalization of membrane proteins in
      kidney epithelial cells.
AB  - Cold preservation of kidneys is commonly used in human transplantation and in
      vitro studies. However, although disruption of the cytoskeleton by cold has been
      demonstrated in cultured cells, the effect of cold treatment on intact kidney is
      poorly understood. In this study, specific antibodies were used to examine the
      effect of hypothermia on the cytoskeletal network and the trafficking of some
      membrane proteins in the urinary tubule. Rat kidneys were cut into thin slices
      (approximately 0.5 mm) that were divided into several groups: (1) some were
      immediately fixed in paraformaldehyde, sodium periodate, and lysine (PLP); (2)
      some were stored at 4 degrees C for 15 min or 4 h before being fixed in cold PLP;
      or (3) after 4 h cold treatment, some slices were rewarmed to 37 degrees C for
      15, 30, and 60 min in a physiologic solution, pH 7.4, and were then fixed in warm
      PLP. Immunofluorescence staining revealed an almost complete disruption of the
      microtubule network in proximal tubules after 15 min cold treatment, whereas
      microtubules in other segments were affected after 4 h. A partial recovery of the
      microtubule network was observed after 60 min rewarming. In contrast, actin
      filaments seemed to be resistant to cold treatment. gp330, aquaporin-2, H+
      ATPase, and the AE1 anion exchanger were all relocated into numerous vesicles
      that were distributed throughout the cytoplasm after hypothermia followed by
      rewarming, whereas Na-K-ATPase retained its basolateral localization. The
      vasopressin-stimulated insertion of aquaporin-2 water channels into the apical
      membrane was inhibited during the initial rewarming period after cold exposure.
      Thus, cold preservation of tissues might impair, at least transiently, the
      polarized membrane expression and function of some transport proteins in renal
      epithelial cells.

PMID- 9527392
TI  - Aminoglycoside antibiotics traffic to the Golgi complex in LLC-PK1 cells.
AB  - Aminoglycoside antibiotics are known to be internalized via endocytosis and have
      been associated with subcellular organelle dysfunction; however, the route of
      intracellular trafficking and their distribution remain largely unknown. To
      address these questions, a Texas Red conjugate of gentamicin (TRG) was
      synthesized for dual-labeling experiments with the endoplasmic reticulum, Golgi,
      and lysosomal markers DiOC6-3, C6-NBD-ceramide, and fluorescent dextrans,
      respectively. Confocal images were overlaid to determine areas of colocalization.
      Initial characterization studies of the fluorescent gentamicin analogue revealed
      that both internalization and accumulation were inhibited by excess unlabeled
      gentamicin. Furthermore, the fluorescent gentamicin label was colocalized with
      unlabeled gentamicin, using immunologic techniques. LLC-PK1 cells were exposed to
      the fluorescent gentamicin in media containing 1 mg/ml labeled gentamicin for 8 h
      and then either fixed or chased with gentamicin-free media for an additional 16
      or 40 h (24 to 48 h total). Studies with fluorescent dextrans revealed rapid
      intracellular colocalization within the endosomal and lysosomal systems. Neither
      endoplasmic reticulum nor mitochondrial colocalization could be detected.
      However, Golgi colocalization was revealed using both confocal and electron
      microscopic techniques at 8 h of TRG incubation, and continued to be present for
      an additional 40 h. Protein synthetic rates were quantified and revealed
      decreased synthesis at the 24-h chase mark. These results suggest that TRG can
      serve as a fluorescent tracer for aminoglycoside trafficking within cells. The
      fluorescent marker remained associated with vesicular structures at all times and
      colocalized with the Golgi apparatus. It is postulated that this early
      association of gentamicin with the Golgi complex may be an avenue for delivery of
      aminoglycosides to other intracellular compartments.

PMID- 9527393
TI  - The N-terminal portion of parathyroid hormone-related protein mediates the
      inhibition of apical Na+/H+ exchange in opossum kidney cells.
AB  - Parathyroid hormone (PTH) and PTH-related protein (PTHrP) can activate a common
      receptor in several different cell types. Both PTH and N-terminal PTHrP peptides
      have been shown to acutely inhibit the apical Na+/H+ exchanger in the renal
      proximal tubule. In this study, the ability of various PTHrP fragments to inhibit
      apical Na+/H+ exchange was investigated. In addition, the signal transduction
      events associated with PTHrP inhibition of apical Na+/H+ exchange in polarized OK
      P cells were characterized. Both PTHrP-(1-34)NH2 and recombinant full-length
      PTHrP-(1-141) inhibited apical Na+/H+ exchange activity by approximately 50%.
      These changes occurred in close temporal association with significant (threefold)
      increases in cellular cAMP accumulation. PTHrP-(1-34)NH2 had no effect on
      intracellular Ca2+, inositol phosphate production, or protein kinase C activity.
      PTHrP peptides, including PTHrP-(38-64)NH2, PTHrP-(67-86)NH2, PTHrP-(102-107)NH2,
      and PTHrP-(107-139)NH2, which lack the PTH-like N terminus, had no effect on the
      antiporter activity or cAMP accumulation. The results demonstrate that the N
      terminal portion of the PTHrP molecule is responsible for inhibition of the
      apical Na+/H+ antiporter in OK-P cells.

PMID- 9527394
TI  - Interaction between high glucose and TGF-beta in cell cycle protein regulations
      in MDCK cells.
AB  - Transforming growth factor-beta (TGF-beta) may mediate high glucose effects in
      renal cells. Thus, Madin-Darby canine kidney cells were studied for the
      modulation of cell cycle regulatory proteins by high glucose (27.5 mM) and TGF
      beta1. We showed that unlike other renal cells, TGF-beta1 mRNA and its
      bioactivity were not induced by high-glucose culture. Furthermore, high glucose
      per se increased cellular proliferation without alterations in cell size. High
      glucose also increased the percentage of cells in the G2/M phase while decreasing
      cells in the G0/G1 phase of the cell cycle. In contrast, TGF-beta1 dose
      dependently (1 to 4 ng/ml) decreased cellular mitogenesis while increasing
      hypertrophy in the cells, especially in the presence of high glucose. TGF-beta1
      also increased the percentage of cells arrested in the G0/G1 phase while
      decreasing cells in the G2/M phase of the cell cycle. Regarding two of the cell
      cycle regulatory proteins, high glucose increased cdc2 kinase activity and
      retinoblastoma protein (pRb) phosphorylation. In contrast, TGF-beta1 decreased
      cdc2 kinase activity and pRb phosphorylation, especially in the presence of high
      glucose. Additionally, glucose dose dependently (5.5, 16.5, 27.5, and 38.5 mM)
      increased type I and II TGF-beta receptor protein expression. In conclusion,
      changes in cdc2 kinase activity and pRb phosphorylation were correlated with high
      glucose and TGF-beta1-induced growth effects in a cell cycle-dependent manner in
      the Madin-Darby canine kidney cells. Furthermore, high glucose may potentiate TGF
      beta1-induced effects by enhancing TGF-beta receptor protein expression.

PMID- 9527395
TI  - Synergistic effect of IL-1alpha, IFN-gamma, and TNF-alpha on RANTES production by
      human renal tubular epithelial cells in vitro.
AB  - Interstitial rejection of renal allografts is associated with infiltrating
      mononuclear cells. Mechanisms leading to this mononuclear cell influx are still
      not fully resolved. The chemokine RANTES (Regulated upon Activation, Normal T
      cell Expressed and Secreted) is chemotactic for monocytes and T cells. In renal
      allograft biopsies of patients undergoing rejection, RANTES is found in
      infiltrating monocytes and T cells, as well as in the tubular epithelium. This
      study analyzes the production of RANTES in vitro by proximal tubular epithelial
      cells (PTEC) after stimulation with the inflammatory cytokines interleukin
      1alpha, (IL-1alpha), interferon-gamma (IFN-gamma), and tumor necrosis factor
      alpha (TNF-alpha). Unstimulated PTEC or PTEC stimulated with the cytokines IL
      1alpha, IFN-gamma, and TNF-alpha alone did not produce detectable amounts of
      RANTES. However, a combination of IFN-gamma and either IL-1alpha or TNF-alpha
      resulted in strong induction of RANTES production up to 2046 +/- 817 pg/ml or
      2595 +/- 525 pg/ml per 1 x 10(5) PTEC, respectively. After stimulation with IL
      1alpha and TNF-alpha, RANTES production was less prominent than the combination
      of IFN-gamma with either IL-1alpha or TNF-alpha, and only detectable in 5 of 7
      PTEC lines tested. The production of RANTES was both dose- and time-dependent and
      was inhibited by cycloheximide, indicating that de novo protein synthesis is
      required. Because the production of RANTES by PTEC is more pronounced in the
      presence of T cell-derived IFN-gamma (in combination with either IL-1alpha or TNF
      alpha), it was hypothesized that RANTES produced by PTEC presumably plays a
      prominent role in the amplification phase of the immune response rather than in
      the initiation phase.

PMID- 9527396
TI  - L-arginine suppresses lipopolysaccharide-induced expression of RANTES in
      glomeruli.
AB  - Endotoxemia leads to the infiltration of inflammatory cells in glomeruli and the
      tubulointerstitium of the kidney. The ultimate mechanisms for this infiltration,
      however, are not entirely clear. In this study, the glomerular formation of the
      chemokine RANTES (regulated upon activation normal T cell expressed and secreted)
      was examined in an in vivo model of endotoxemia to evaluate the role the local
      release of chemokines might play in the regulation of this inflammatory cell
      infiltrate. Since the beneficial effects of nitric oxide (NO) on immune-mediated
      tissue injury have been reported, we also examined possible interactions between
      the chemokine RANTES and the L-arginine/NO pathway. To induce endotoxemia, rats
      were injected intraperitoneally with lipopolysaccharide (LPS). Glomeruli were
      isolated over a 24-h time period, and RANTES was assessed by Northern blotting, a
      chemotactic assay, and a specific enzyme-linked immunosorbent assay. The
      chemokine release was associated with increased glomerular infiltration of
      monocytes/macrophages. LPS also stimulated the mRNA expression of inducible NO
      synthase and increased the release of nitrite into the supernatants of isolated
      glomeruli. Supplementation of L-arginine intake increased the release of
      glomerular nitrite and reduced glomerular RANTES expression after the injection
      of LPS. Inhibition of the L-arginine/NO pathway by the unspecific NO synthase
      inhibitor N(G)-nitro-L-arginine methylester significantly increased glomerular
      RANTES mRNA expression and the number of infiltrating glomerular macrophages.
      These data demonstrate that L-arginine suppresses glomerular RANTES formation and
      suggest that the chemokine-mediated recruitment of glomerular macrophages in LPS
      induced endotoxemia can be modulated by the L-arginine/NO pathway.

PMID- 9527398
TI  - Effects of combination therapy with enalapril and losartan on the rate of
      progression of renal injury in rats with 5/6 renal mass ablation.
AB  - Angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor
      antagonists (AT1RA) slow the rate of progression of experimental renal disease.
      Although the end result of both classes of drugs is to block the renin
      angiotensin system (RAS), ACEI and AT1RA act at different sites in the RAS
      cascade. The aim of this study was to compare the effects of an ACEI (enalapril)
      and AT1RA (losartan), alone or in combination, in slowing the progression of
      experimental renal disease in a model of reduced renal mass. Two weeks after 5/6
      renal ablation, rats were divided into five groups matched for body weight,
      systolic BP (SBP), and urinary protein excretion rate (UprotV). The effects on
      SBP and UprotV of treatment with 25 and 40 mg/L enalapril (groups I and II; both
      n = 7), 180 mg/L losartan (group III, n = 8), or a combination of enalapril (25
      mg/L) + losartan (180 mg/L) (group IV, n = 9) versus vehicle (group V, n = 9)
      were studied for 12 wk. Remnant kidneys were then assessed histologically for
      evidence of focal and segmental glomerulosclerosis and hyalinosis (FSGS), and
      interstitial fibrosis. There were no significant differences (NSD) in body weight
      among the groups at any time. Combination therapy reduced SBP (122 +/- 8 mmHg)
      significantly at 12 wk to levels similar to losartan (127 +/- 3 mmHg) or
      enalapril (40 mg/L) alone (124 +/- 5 mmHg) (P < 0.05 versus vehicle controls).
      With equivalent antihypertensive effects, no differences in frequency of FSGS
      were discerned among the treatment groups (groups II through IV; F = 1.7, NSD).
      Tubulointerstitial injury scores followed a similar pattern. BP was highly
      correlated with the extent of FSGS, both among individual rats (r = 0.68, P =
      0.05) and the group means (r = 0.99, P = 0.001). We conclude that the
      renoprotective effects of enalapril, losartan, or combination therapy are similar
      in this model over the 12 wk of the study, and are closely related to the
      magnitude of their antihypertensive effects.

PMID- 9527397
TI  - Expression of PDGF alpha-receptor in renal arteriosclerosis and rejecting renal
      transplants.
AB  - Platelet-derived growth factor (PDGF) plays an important role in renal disease.
      We have recently demonstrated that in healthy mature human kidney, PDGF alpha
      receptor expression is largely restricted to interstitial cells. The study
      presented here assesses the expression of PDGF alpha-receptor in 18 mature adult
      kidneys with arteriosclerosis from individuals with no clinically evident history
      of renal disease other than localized neoplasia, in 13 kidneys with irreversible
      transplant rejection, and in a series of renal transplant biopsies composed of
      examples of both severe and absent rejection, by in situ hybridization and
      immunocytochemistry. Strong focal or diffuse expression of PDGF alpha-receptor
      mRNA and protein was noted in some intimal cells of intrarenal arterial vessels
      exhibiting signs of arteriosclerosis and/or vascular rejection. By double
      immunostaining, it could be shown that these cells were neither endothelial cells
      nor infiltrating leukocytes. The cells were most often identified as smooth
      muscle by colabeling for the smooth muscle cell-specific protein SM22alpha and
      less commonly for alpha-smooth muscle actin. There was also a population of PDGF
      alpha-receptor-expressing cells that failed to colabel with any of these markers,
      and hence remain of uncertain histogenesis. These intimal cells were generally
      negative for several other markers of differentiated smooth muscle cells, i.e.,
      calponin and desmin. Near these PDGF alpha-receptor-positive intimal cells,
      expression of PDGF A-chain, an alpha-receptor ligand, was demonstrated in
      endothelial, intimal, and/or medial cells. Prominent PDGF alpha-receptor mRNA and
      protein expression also was noted in areas of interstitial fibrosis and in some
      glomeruli, in particular those with segmental glomerulosclerosis or fibrotic
      crescents. Double immunolabeling for PDGF alpha-receptor and alpha-smooth muscle
      actin confirmed that most of these latter PDGF alpha-receptor-positive cells were
      interstitial myofibroblasts or mesangial cells, or both. In summary, these data
      demonstrate widespread expression of PDGF alpha-receptor in renal cell types
      involved in fibrotic and sclerosing processes. The data also show that PDGF alpha
      receptor expression identifies a unique population of phenotypically altered
      vascular smooth muscle cells, which appear to be involved in the vascular
      response to injury.

PMID- 9527399
TI  - Tubulointerstitial disease in aging: evidence for underlying peritubular
      capillary damage, a potential role for renal ischemia.
AB  - Aging is associated with a progressive decline in renal function and the
      development of glomerulosclerosis and interstitial fibrosis. Although many
      studies have addressed the cellular mechanisms of age-related glomerulosclerosis,
      less is known about the tubulointerstitial fibrosis. In this study, aging (24 mo)
      rats develop tubulointerstitial fibrosis characterized by tubular injury and
      focal tubular cell proliferation, myofibroblast activation, macrophage
      infiltration with increased immunostaining for the adhesive proteins osteopontin
      and intercellular adhesion molecule-1, and collagen IV deposition. Aging rats
      demonstrated immunostaining for endothelial nitric oxide synthase (eNOSIII) in
      renal tubular epithelial cells and infiltrating mononuclear cells in areas of
      tubulointerstitial injury, with a relative loss of staining of the peritubular
      capillaries compared with young rats. The aging rats also displayed focal loss of
      peritubular capillaries (as noted by focally decreased RECA-1 and OX-2 staining)
      in areas of tubulointerstitial injury. The areas of fibrosis and hypocellularity
      were associated with increased apoptosis of tubular and interstitial cells
      compared with young (3 mo) rats (25.4 +/- 5.3 versus 3.5 +/- 2.5 TUNEL-positive
      cells/0.25 mm2 in old versus young rats, P = 0.0001). It is concluded that
      tubulointerstitial fibrosis in aging is an active process associated with
      interstitial inflammation and fibroblast activation. The progressive loss of
      cells in areas of fibrosis may be due to accelerated apoptosis. Furthermore, the
      tubulointerstitial injury may be the consequence of ischemia secondary to
      peritubular capillary injury and altered eNOS expression.

PMID- 9527401
TI  - Survival in renal vascular disease.
AB  - Renal artery stenosis (RAS) is a relatively uncommon but important potentially
      reversible cause of renal failure. Little is known about the natural history of
      ischemic renal disease secondary to RAS. In previous reports, these researchers
      examined the incidence and risk factors associated with RAS. The study presented
      here investigates the long-term follow-up of these patients, specifically the
      effect of RAS on 4-yr, all-cause mortality in a group of 1235 patients undergoing
      diagnostic cardiac catheterization and abdominal aortography. A total of 1235
      consecutive patients undergoing cardiac catheterization also underwent an
      abdominal flush aortogram. Significant RAS was considered present if one or more
      renal artery had 50% or greater narrowing in luminal diameter. Four-year
      unadjusted survival for patients with RAS was 65% compared with 86% for patients
      undergoing catheterization without significant RAS. Factors associated with
      decreased 4-yr survival included increased age, increased serum creatinine,
      presence of RAS, peripheral vascular disease, congestive heart failure, diabetes,
      hypertension, and reduced ejection fraction. Using the Cox proportional hazards
      model, the factors associated with decreased 4-yr survival were the presence of
      significant RAS, reduced ejection fraction, elevated serum creatinine, and
      symptoms of congestive heart failure. These observations indicate that the
      presence of significant RAS is a strong independent predictor of 4-yr survival in
      this patient population.

PMID- 9527400
TI  - Failure of antioxidant therapy to attenuate interstitial disease in rats with
      reversible nephrotic syndrome.
AB  - The present two studies were designed to determine whether oxidized LDL
      contributes to the tubulointerstitial changes seen in rats during the acute phase
      of acute puromycin aminonucleoside nephrosis (PAN). In the single-dose study,
      rats were given one injection of puromycin aminonucleoside (PA; 15 mg/100 g body
      wt) and killed 1, 2, or 3 wk thereafter. The four animal groups were saline
      controls, PAN controls, PAN plus probucol, and PAN plus lovastatin. This study
      showed that the addition of probucol significantly reduced the mean levels of
      serum cholesterol and renal lipid-peroxidation products, an effect not seen with
      lovastatin therapy. Compared with saline controls, PAN controls had a significant
      increase in total kidney collagen (7.9 +/- 1.2 versus 5.9 +/- 0.6 mg/kidney at 3
      wk). Neither probucol nor lovastatin therapy attenuated the interstitial
      inflammation or fibrosis. In the multidose study, rats were given the same
      initial PA dose and were uninephrectomized on day 12. They were killed on day 35
      after two smaller PA doses were given on days 16 and 23. Animal groups were
      saline controls, PAN controls, PAN plus probucol, and PAN plus vitamin E. Hepatic
      lipid-peroxidation products were significantly lower in the probucol-treated, but
      not in the vitamin E-treated, PAN groups when compared with the PAN controls.
      Neither probucol nor vitamin E prevented the increase in total kidney collagen
      that was observed in the PAN control group (7.4 +/- 0.7, 10.1 +/- 2.6, and 9.3 +/
      1.8 mg of collagen/kidney, respectively, versus 5.4 +/- 0.5 mg/kidney for the
      saline controls). Renal cortical mRNA levels for matrix-encoding genes and
      protease inhibitors were similar in the three nephrotic groups. Transforming
      growth factor-beta1 mRNA levels were highly variable within each group and not
      significantly different at day 35, but showed a significant positive correlation
      with the degree of albuminuria (r = 0.70). The present results demonstrate that
      the treatment of acutely nephrotic rats with antioxidant therapy did not
      attenuate interstitial inflammation or fibrosis. We speculate that other factors,
      possibly a consequence of proteinuria itself, are the predominant pathogenetic
      mediators of the tubulointerstitial damage in acute nephrotic syndrome.

PMID- 9527402
TI  - A multicenter comparison of dialysis membranes in the treatment of acute renal
      failure requiring dialysis.
AB  - The mortality of patients with acute renal failure (ARF) remains high, and in
      several large studies approaches 60%. This mortality is particularly high in
      patients with ARF who require dialysis and has not changed substantially over
      several years, despite the introduction of major advances in monitoring and
      treatment. Increasing prevalence of comorbidities has been suggested as the major
      factor in this persistently high mortality. This study investigates the potential
      role of the dialysis membrane on patient outcome in a prospective multicenter
      study of 153 patients with ARF requiring dialysis. The membrane assignment was
      made in alternating order and was limited to membranes with low complement
      activation (Biocompatible [BCM]) and cellulosic, high complement activation
      (Bioincompatible [BICM]). Both types of membranes were low-flux membranes.
      Patients were dialyzed with the assigned membrane until recovery, discharge from
      hospital, or death. The severity of illness of each patient was assessed using
      the APACHE II score at the time of initiation of dialysis. A logistic regression
      analysis was used to adjust for the APACHE II score. The results of the study
      showed a statistically significant difference in survival (57% in patients on
      BCM, 46% in patients on BICM; P = 0.03) and in recovery of renal function (64% in
      patients on BICM and 43% in patients on BICM; P = 0.001). These differences were
      particularly marked in the patients who were nonoliguric (>400 ml/d of urine
      output) at initiation of the study. In the subset of patients who were
      nonoliguric at the start of dialysis, a larger fraction (70%) became oliguric
      after initiating dialysis on a BICM membrane, in contrast to 44% who were
      initiated on a BCM membrane (P = 0.03). It is concluded that the biocompatibility
      of the dialysis membrane plays a role in the outcome of patients with ARF,
      particularly those who are nonoliguric at the time of initiation of dialysis.

PMID- 9527403
TI  - Mode of dialysis therapy and mortality in end-stage renal disease.
AB  - Despite considerable differences in technique and blood purification
      characteristics, hemodialysis and peritoneal dialysis have been thought to have
      similar patient outcomes. An inception cohort of 433 end-stage renal disease
      patients was followed prospectively for a mean of 41 mo. The outcomes of
      hemodialysis (HD) and peritoneal dialysis (PD) patients were compared using
      intention to treat analysis based on the mode of therapy at 3 mo. After
      adjustment for PD patients less likely to have chronic hypertension and more
      likely to have diabetes, ischemic heart disease, and cardiac failure at baseline
      (P < 0.05), a biphasic mortality pattern was observed. For the first 2 yr, there
      was no statistically significant difference in mortality. After 2 yr, mortality
      was greater among PD patients with an adjusted PD/HD hazard ratio of 1.57 (95%
      confidence interval [CI], 0.97 to 2.53). Both the occurrence (adjusted hazards
      ratio 6.87 [95% CI, 2.01 to 23.5]) and the direction (toward PD, adjusted hazards
      ratio 6.25 [95% CI, 1.54 to 25]) of a therapy switch were subsequently associated
      with mortality after 2 yr. Progressive clinical and echocardiographic cardiac
      disease were not responsible for this late mortality. Lower mean serum albumin
      levels in PD patients in the first 2 yr of therapy (3.5 +/- 0.5 versus 3.9 +/-
      0.5 g/dl, P < 0.0001) accounted for a large proportion of the increase in
      subsequent mortality. Hemodialysis has a late survival advantage over peritoneal
      dialysis; antecedent hypoalbuminemia is a major marker of the increased late
      mortality in PD patients.

PMID- 9527404
TI  - Aminoguanidine inhibits advanced glycation end products formation on beta2
      microglobulin.
AB  - Because advanced glycation end products (AGE)-modified beta2-microglobulin (AGE
      beta2M) is a dominant constituent of amyloid in dialysis-related amyloidosis
      (DRA), AGE-beta2M may be directly involved in the pathobiology of DRA. In
      experimental diabetes mellitus, blocking the formation of AGE prevents AGE
      mediated tissue damage. In this study, it is postulated that similar
      pharmacologic intervention may be beneficial in DRA. Aminoguanidine, a
      nucleophilic hydrazine compound that prevents AGE formation on collagen, may have
      a similar effect on the advanced glycation of beta2M. To test this hypothesis,
      beta2M was incubated in vitro with 50 or 100 mM D-glucose for 3 wk in the
      presence and absence of incremental concentrations of aminoguanidine. On the
      basis of enzyme-linked immunosorbent assay and immunoblots using anti-AGE-keyhole
      limpet hemocyanin antibody, aminoguanidine inhibited glucose-induced N(epsilon)
      (carboxymethyl)lysine formation on beta2M. At aminoguanidine-glucose molar ratios
      of 1:8 to 1:1, 26 to 53% inhibition occurred. Fluorospectrometry examination
      showed that aminoguanidine also inhibited the formation of fluorescent AGE on
      beta2M in a dose-dependent manner. At aminoguanidine-glucose molar ratios of 1:8
      to 1:1, fluorescent product generation was inhibited by 30 to 70%. Furthermore,
      aminoguanidine suppressed the AGE formation on beta2M bound to AGE-modified
      collagen. If aminoguanidine is similarly active in vivo, this compound may be of
      clinical utility for treating DRA in patients on maintenance dialysis.

PMID- 9527405
TI  - Simplified measurement of intra-access pressure.
AB  - The measurement of intra-access pressure (P[IA]) normalized by mean arterial BP
      (MAP) helps detect venous outlet stenosis and correlates with access blood flow.
      However, general use of P(IA)/MAP is limited by time and special equipment costs.
      Bernoulli's equation relates differences between P(IA) (recorded by an external
      transducer as PT) and the venous drip chamber pressure, PDC; at zero flow, the
      difference in height (deltaH) between the measuring sites and fluid density
      determines the pressure deltaPH = P(IA) - P(DC) Therefore, P(DC) and PT
      measurements were correlated at six different dialysis units, each using one of
      three different dialysis delivery systems machines. Both dynamic (i.e., with
      blood flow) and static pressures were measured. Changes in mean BP, zero
      calibration errors, and hydrostatic height between the transducer and drip
      chamber accounted for 90% of the variance in P(DC), with deltaPH = -1.6 + 0.74
      deltaH (r = 0.88, P < 0.001). The major determinants of static P(IA)/MAP were
      access type and venous outflow abnormalities. In grafts, flow averaged 555 +/- 45
      ml/min for P(IA)/MAP > 0.5 and 1229 +/- 112 ml/min for P(IA)/MAP < 0.5. DeltaPH
      varied from 9.4 to 17.4 mmHg among the six centers and was related to deltaH
      between the drip chamber and the armrest of the dialysis chair. Concordance
      between values of P(IA)/MAP calculated from PT and from P(DC) + deltaPH was
      excellent. It is concluded that static P(DC) measurements corrected by an
      appropriate deltaPH can be used to prospectively monitor hemodialysis access
      grafts for stenosis.

PMID- 9527406
TI  - New criteria for management of catheter infections in peritoneal dialysis
      patients using ultrasonography.
AB  - Catheter-related infection is one of the most important causes of technical
      dropout in peritoneal dialysis patients. Both the type of cultured organism and
      the extent of inflammation are well known prognostic factors for the outcome of
      these infections. From December 1994 to November 1996, 96 catheter-related
      infections without simultaneous peritonitis occurred in 49 of 86 peritoneal
      dialysis patients treated in this study. During the observation period, only
      single-cuff catheters were used. Staphylococcus aureus was the most common
      organism cultured (51%). Involvement of the tunnel was diagnosed by sonography in
      57.1% of all Staphylococcus aureus cases, but only in 26.1% of Staphylococcus
      epidermidis-related exit-site infections. Ten of the 96 catheter-related
      infections (10.4%) resulted in catheter loss. Catheter removal was necessary only
      in cases of deep tunnel infection caused by Staphylococcus aureus. The number of
      gram-negative catheter infections was too small to allow conclusive analysis.
      Although sonography of the catheter tunnel is now well established in the early
      diagnosis of tunnel infections, no clear guidelines exist for management of these
      infections. In this study, patients with deep tunnel infection who did not
      require catheter removal showed a significant decline of the hypoechogenic area
      around the cuff (from 7.02 +/- 0.70 to 3.75 +/- 1.04 mm, P < 0.002) 2 wk after
      initiation of therapy. No significant decline was observed in patients who later
      lost their catheters. On the basis of these data, it is concluded that in cases
      of exit-site and superficial tunnel infection, conservative treatment should be
      performed. In cases of deep tunnel infection without peritonitis caused by
      Staphylococcus aureus, antibiotic treatment should be started and sonographic
      examination should be performed every second week. If the hypoechogenic area
      around the cuff decreases (> 30%), conservative treatment should be prolonged. In
      cases without sonographic improvement (< 30%) 2 wk after therapy, catheter
      removal is recommended.

PMID- 9527407
TI  - Pretransplant test-dose pharmacokinetic profiles: cyclosporine microemulsion
      versus corn oil-based soft gel capsule formulation.
AB  - The purpose of this study was to compare the accuracy of pretransplant test-dose
      pharmacokinetic (PK) profiling after administration of the microemulsion (CsA-ME;
      Neoral) versus the corn oil-based (CsA-GC; Sandimmune) gel capsule formulations
      of cyclosporin A (CsA) to estimate posttransplant CsA bioavailability and to
      individualize starting drug doses. The absolute oral bioavailability (F),
      clearance rate (CL), average blood concentration (C[av]), peak concentration
      (Cmax), and time to Cmax (tmax) values were calculated from paired intravenous
      and oral pretransplant PK profiles of renal transplant candidates, using CsA-GC
      (n = 70) or CsA-ME (n = 70) administration. The initial posttransplant oral CsA
      dose was estimated by linear extrapolation of the observed pretransplant value to
      the target concentration. Because higher mean F (P < 0.0001), but not CL, values
      were observed in end-stage renal disease patients after CsA-ME compared with CsA
      GC treatment, the predicted starting doses for each therapy were markedly
      different (P < 0.01). From posttransplant days 5 to 7, 54% of patients treated
      with CsA-ME had a mean dose-normalized C(av) (C(av)/dose, D) value within 20% of
      the target concentration, compared with 42% of patients treated with CsA-GC (P =
      0.03). Administration of the predicted oral dose of CsA-ME produced a Cmax > 700
      ng/ml in 90% of patients from days 2 to 4, and in 97% from days 5 to 7, whereas
      administration of the predicted oral dose of CsA-GC produced a Cmax > 700 ng/ml
      in only 64 and 82% of patients during these same time periods, respectively (both
      P < 0.05). The mean estimated posttransplant F value of CsA-ME was significantly
      higher than that of CsA-GC; even at postoperative day 5 the value for CsA-GC was
      significantly lower than the pretransplant estimate (P < 0.01). Therefore, CsA-ME
      pretransplant PK profiles yield more accurate predictions for appropriate
      starting drug doses than those of CsA-GC.

PMID- 9527408
TI  - Anesthetic effects on the glycerol model of rhabdomyolysis-induced acute renal
      failure in rats.
AB  - Isoflurane, the most widely used inhalational anesthetic, releases inorganic
      fluoride during its metabolism by the cytochrome P450 system. Recent experimental
      data indicate that when cultured proximal tubular cells are exposed to inorganic
      fluoride, they become relatively resistant to myoglobin- and ATP depletion
      mediated attack. The present study was undertaken to assess whether isoflurane
      anesthesia might confer in vivo cytoprotection, possibly by causing renal tubular
      inorganic fluoride exposure, thereby mitigating a combined myoglobin/ATP
      depletion model of acute renal failure (glycerol-induced ARF). Rats were injected
      with hypertonic glycerol (50%; 9 ml/kg, intramuscularly) while undergoing 4 h of
      isoflurane anesthesia. Glycerol-injected rats anesthetized with a virtually
      nondefluorinated inhalational anesthetic (desflurane) or with a nonfluorinated
      anesthetic (pentobarbital) served as controls. The severity of ARF was assessed
      24 h later (blood urea nitrogen, plasma creatinine [Cr], and renal histology).
      Anesthetic effects on extrarenal injury (plasma creatine phosphokinase, lactate
      dehydrogenase, and hematocrit levels), acute intrarenal heme loading (cast
      formation), and BP during the initiation phase of renal injury (0 to 4 h after
      glycerol injection) were also assessed. Glycerol induced severe ARF under
      pentobarbital anesthesia (Cr, 2.8 +/- 0.3 mg/dl; severe tubular necrosis).
      Somewhat worse azotemia, but comparable tubular necrosis, resulted with
      desflurane use. Conversely, glycerol plus isoflurane anesthesia induced only mild
      renal damage (Cr, 0.9 +/- 0.1, minimal tubular necrosis; P < 0.01). This
      reduction apparently was not due to differences in degrees of muscle necrosis,
      hemolysis, acute renal heme loading, or BP during the initiation phase of ARF,
      suggesting that a direct renal mechanism was operative. These results: (1)
      underscore that differing anesthetics can profoundly alter the expression of
      experimental renal injury; (2) raise the intriguing possibility that isoflurane
      could potentially protect surgical/trauma patients from rhabdomyolysis-induced
      ARF; and (3) further support the concept that renal fluoride exposure may confer
      proximal tubular cytoprotective effects.

PMID- 9527410
TI  - Hypertension in pregnancy.

PMID- 9527409
TI  - Precision of plasma clearance of iohexol for estimation of GFR in patients with
      renal disease.
AB  - The choice of the optimal method for the measurement of renal function is based
      on the accuracy and the precision of the technique. The plasma clearance of
      nonradioactive iohexol has been proposed as a reliable alternative to renal
      clearance of inulin for estimation of GFR. However, the precision of this method
      in estimating GFR in patients with renal disease has not been determined so far.
      This issue was assessed by determining plasma clearance of iohexol on three
      different occasions during a 12-d period in 24 patients with renal disease and a
      wide range of renal function (creatinine clearance: 14 to 104 ml/min per 1.73
      m2). Overall, the mean intraindividual coefficient of variation was 5.59%, and
      the reproducibility was 6.28%. The precision of the method also applied to the
      subgroup of patients with moderate-to-severe renal insufficiency, because a low
      coefficient of variation (5.71%) and a high reproducibility (6.57%) were found in
      patients with GFR < or =40 ml/min per 1.73 m2. It was also shown that the
      precision of GFR measurement by the plasma clearance of iohexol is not affected
      by the gender. These findings indicate that the method of plasma clearance of
      iohexol allows a good precision in the estimation of GFR in patients with normal
      renal function and different degrees of renal dysfunction.

PMID- 9527411
TI  - Crush injuries with impairment of renal function. 1941.

PMID- 9527412
TI  - [Diagnosis of contagious bovine pleuropneumonia: problems and recent
      developments].
AB  - While it is easy to diagnose contagious bovine pleuropneumonia (CBPP) in an
      animal in the acute clinical stage, subacute and chronic forms are more difficult
      to diagnose. Recourse to laboratory tests is essential to confirm any suspicion
      of CBPP. As standard diagnostic procedures (isolation, culture, biochemical
      tests, serological tests) are lacking in specificity and sensitivity,
      improvements are needed. Progress in molecular biology techniques has led to new
      tests, among which are the polymerase chain reaction (PCR) and the enzyme-linked
      immunosorbent assay (ELISA) using monoclonal antibodies. Application of these
      techniques to CBPP offers a number of advantages, and has considerably enhanced
      the specificity and sensitivity of diagnosis.

PMID- 9527414
TI  - [Contagious agalactia of small ruminants: epidemiology, diagnosis and control].
AB  - Contagious agalactia of small ruminants is a syndrome which affects mainly the
      mammary glands, joints and eyes. The principal causal agents are Mycoplasma
      agalactiae in sheep and M. agalactiae, M. mycoides subsp. mycoides large colony
      type and M. capricolum subsp. capricolum in goats. In addition, M. putrefaciens
      can produce a similar clinical picture, particularly in goats. Contagious
      agalactia occurs on all five continents and is often enzootic. These infections
      are chronic in animals and in flocks. Symptomless shedding of mycoplasmas, mainly
      in the milk, may persist for a long time. Associated with carriage in the ears of
      healthy animals, these insidious infections are difficult to diagnose and
      control. The sale of carrier animals and contact during transhumance are the main
      modes of transmission between flocks, while transmission within a flock occurs
      through contact, suckling and milking. This review discusses clinical features,
      epidemiology, treatment, prevention and control.

PMID- 9527415
TI  - Severe autoimmune diseases: a new target for bone marrow transplantation. Sandoz
      Keystone symposium, January 15-21, 1996. Abstracts.

PMID- 9527413
TI  - [Strategies for prevention and eradication of contagious bovine pleuropneumonia
      with or without vaccination].
AB  - Contagious bovine pleuropneumonia (CBPP) offers, like rinderpest, the paradox of
      having been eradicated from some countries (north-western Europe, the United
      States of America) before the nature of the pathogenic agent was known. As a
      preventive measure, inoculation of pathogenic material was used but success
      varies due to strategic inadequacies. The same applies to vaccination with more
      or less attenuated live strains of Mycoplasma mycoides subsp. mycoides. Many
      ideas for prophylaxis have been suggested. Disease-free countries must apply the
      recommendations of the International Animal Health Code of the Office
      International des Epizooties (OIE), including those concerning the operation of
      epidemiological surveillance systems. Infected countries (or regions) select one
      of the following courses of action, depending on epidemiological, geographic,
      economic and social circumstances: Slaughter of affected and in-contact animals.
      This radical, simple and effective solution cannot be applied everywhere,
      particularly in a number of developing countries which have pastoral economies.
      Slaughter of affected animals and vaccination of those in contact. This method,
      which actually perpetuates the infection, is unfortunately still used widely.
      Preventive vaccination of healthy animals, coupled with the slaughter of affected
      animals and/or revaccination of those exposed to infection. This method controls
      the situation if outbreaks are detected efficiently and combated energetically.
      The tactical approach for disease-free and infected areas should continue to be
      that of large-scale and repeated vaccination, recommended since 1970 and the
      efficiency of which has been proved. This approach can lead to eradication when
      maintained for at least three years and applied to an entire infected region or
      country. A country is recognised as free from infection under rules adopted by
      the OIE in 1995.

PMID- 9527416
TI  - [Infection risk and efficacy of clinical selection techniques for volunteer blood
      donors].
AB  - One of the objectives of predonation selection is to exclude blood donors with
      possible infection. Our aim was to evaluate the efficacy of the different blood
      donor selection techniques. The approach chosen for this review of literature was
      the best evidence synthesis. A bibliographic search was carried out to identify
      all articles on the subject published between 1986 and 1996 which presented
      quantitative results of evaluation. Only nine relevant studies were selected.
      These referred to self exclusion before interview, health history interview and
      confidential deferral after donation. None of the articles evaluated the physical
      examination. The results suggested an efficacy for self exclusion before
      interview. One study considered the blood donor selection and compared various
      ways of combining self exclusion before interview, health history interview and
      confidential deferral after donation. No combination emerged as more effective
      than the others. This analysis shows that the efficacy of predonation blood donor
      selection applied to transfusion transmitted infections has not been evaluated
      adequately. The different techniques of blood donor selection must be considered
      as public health actions and hence evaluated according to a rigorous methodology
      using valid criteria.

PMID- 9527417
TI  - [Quantitative bacteriological evaluation of a method for skin disinfection in
      blood donors].
AB  - Skin disinfection at the site of venipuncture is a critical point in every blood
      transfusion collection procedure, as it contributes to ensure the bacterial
      safety of transfusion. Quantitative and qualitative analysis of bacteria present
      in the antecubital fossae before and after skin disinfection may be one method of
      assessing the anti-bacterial efficiency of disinfection. Swab culture systems and
      contact plates are the two techniques usually employed for this purpose. A
      washing and swabbing technique was used to quantify bacteria before and skin
      disinfection of the antecubital fossae in blood donors. This contra-placebo study
      was carried out on 32 donors, each of whom served as his own control, with a
      random choice of test arm and opposing control arm. Bacterial counts were
      determined in the antecubital fossae without skin disinfection (control, n = 32)
      and after a 3 step skin preparation procedure (cleaning, wiping, disinfection)
      using placebo (distilled water, n = 16) or an antiseptic product (mixture of
      chlorexidine, benzalkonium chloride and benzylic alcohol, n = 16). The absence of
      a statistical difference in bacterial counts between the right and left
      antecubital fossae without disinfection was controlled in a preliminary study of
      20 subjects. Mean bacterial counts were 25,000/cm2 and 27,400/cm2 respectively
      for aerobic and anaerobic bacteria before disinfection, with a wide variation in
      results between individuals. When using placebo, preparation of the venipuncture
      site by the 3 step method (cleaning, wiping, disinfection) resulted in a non
      significant mean reduction of 0.56 log in aerobic and anaerobic bacteria. Using
      the antiseptic product, the same method resulted in a significant mean reduction
      of 1.8 and 1.7 log respectively in aerobic (p = 0.015) and anaerobic flora (p =
      0.005). On an average, 2,750 aerobic bacteria/cm2 and 2,910 anaerobic
      bacteria/cm2 remained after disinfection, while qualitative analysis showed that
      disinfection suppressed the transitory flora in all cases but left part of the
      resident flora in 12/16 cases. These findings are comparable to those of other
      studies carried out to evaluate this kind of technique for the disinfection of
      operation sites. In comparison with other techniques classically employed for
      this type of evaluation (swab systems or contact plates), the method used in this
      study was the advantage of allowing the quantification of the reduction in
      bacteria. Hence this method could be employed for comparative assessment of skin
      disinfection techniques with the aim of improving their anti-bacterial efficiency
      and could also make possible the definition of a minimum bacterial count
      (resident flora) to be obtained in all cases after disinfection.

PMID- 9527418
TI  - [Pilot study of the characteristics of transfused patients and utilized labile
      blood products].
AB  - The aim of this study was to describe blood recipients and blood components
      transfused during the first 24 hours in 13 French hospitals. We included all
      blood recipients who had not had any blood transfusion within the past six
      months. Recipients were screened for red cell alloantibodies, the alanine
      aminotransferase activity and specific viral markers (hepatitis B and C, Human
      Immunodeficiency Virus). Eligible patients represented 47% of the all transfused.
      Among the 371 patients included, 57% were males and 71% were transfused in a
      surgical unit. Alloantibodies, non specific and specific viral markers were
      detected in 3%, 19% and 2% respectively. Among the patients included, 42 received
      172 autologous units. In total, 1056 allogeneic units (an average of 3 units per
      patient) were transfused; blood products were leucocyte-depleted (49%) or
      leucocyte-poor (20%); 54% of red cell units were matched for antigens Rh and
      Kell. Neoplasms were the most frequently reported disease for which patients were
      transfused. This study provides baseline blood transfusion information on
      recipients and blood utilization for a specific period in French hospitals.
      Following this study, a national study will allow the clarification of the
      characteristics, for instance the surgical procedures requiring transfusion.

PMID- 9527419
TI  - [Analysis of transfusion incident reports filed at 15 blood transfusion centers
      and health facilities during 17 months. Groupe Receveurs de laSFTS].
AB  - The principal result of the development of hemovigilance since 1994 has been the
      declaration of undesirable effects likely to be due to transfusions of labile
      blood products. Using the 1,694 cases of undesirable effects registered, it
      seemed worthwhile to us to analyze the distribution of the signs noticed, their
      frequency and the types of blood products responsible. This analysis allowed us
      to observe that the majority of reactions were shivery-feverish (47%) or allergic
      (24%). Most of them are linked to platelet concentrate transfusions especially
      simple donor platelets (with a frequency of ten reactions for thousand apheresis
      platelet concentrates transfused). In this study the frequency of undesirable
      effects reported is 2 per 1,000 apheresis platelet concentrate transfusions.
      Further investigations are necessary to determine the physiological mechanisms of
      these reactions and to estimate the degree to which transfusions are responsible
      for their occurrence.

PMID- 9527420
TI  - [Consequences for labile blood products of leukocyte depletion by whole blood
      filtration using the Leucoflex LST1 in-line filter. Evaluation of the Leucoflex
      LST1 filter].
AB  - The aim of this study is to evaluate the effects of whole blood filtration after
      a storage time of 20-24 hours at laboratory temperature using the in line filter
      Leucoflex LST1. The study concerns 49 blood donations in which we studied
      leukocyte depletion, proteins (IgG, IgA, IgM, haptoglobin, C3, C4), coagulation
      factors (fibrinogen, factors XII, XI, IX, VIII, V, proteins S and C, plasminogen,
      tPA, D-Dimers, PDF) at day 1, the parameters of conservation (ATP, 2-3 DPG, extra
      cellular potassium, haemolysis, pH) of red blood cell concentrates (RCCs) and
      bacteriological sterility at day 1 and 42. Despite a correct leukocyte depletion
      (mean depletion of 3.96 log), a 10 fold higher mean level of residual
      leukocytes/unit than with buffy coat poor RCC filtration (0.514.10(6) vs
      0.051.10(6)) is observed. Moreover a lot of concentrates are not in accordance
      with French regulations (7/42 with more than 1.10(6) leukocytes/unit). The
      variation of the rates of IgG, IgA, IgM, haptoglobin, C4 and protein C is not
      significant. For the others there is a slight decrease with a mean level
      remaining in a physiological range. No sign of activation is noted. The sterility
      assays remain negative and the RCC conservation is not altered. In conclusion,
      even if the quality of the leukocyte depletion is not satisfactory in our study
      and has to be stated more precisely by multicenter studies, the whole blood
      filtration does not alter the quality of the derived components and allows us
      obtain RCC in a bigger volume and containing more haemoglobin than with the
      classical procedure after removing the buffy-coat [10].

PMID- 9527421
TI  - Proceedings of the official satellite symposium of the 2nd Congress of the
      European Association of Clinical Pharmacology and Therapeutics (EACPT): Clinical
      pharmacology of P-glycoprotein and related transporters. Part I. Berlin, Germany,
      September 16, 1997.

PMID- 9527422
TI  - Using 'Best Evidence' in clinical practice.

PMID- 9527423
TI  - The 2nd National AIDS Malignancy Conference. Bethesda, Maryland, USA. April 6-8,
      1998. Abstracts.

PMID- 9527425
TI  - Clinical features of trigeminal nerve-sheath tumor in 10 dogs.
AB  - Nerve-sheath tumor was diagnosed in 10 dogs with clinical signs of unilateral
      trigeminal nerve dysfunction. Unilateral temporalis and masseter muscle atrophy
      were present in all cases. An enlarged foramen and distorted rostral petrous
      temporal bone were seen with computed tomography imaging in one case. Magnetic
      resonance imaging was used to identify the lesion accurately in seven cases.
      Surgery was performed for biopsy and lesion removal in three cases. Cases not
      treated had a progressive course eventually resulting in euthanasia or death. Of
      the cases treated surgically, one case is alive without disease progression 27
      months after surgery. Survival times of the nontreated cases ranged from five to
      21 months.

PMID- 9527424
TI  - Multilobular osteochondrosarcoma in 39 dogs: 1979-1993.
AB  - Thirty-nine, older, large-breed dogs with multilobular osteochondrosarcoma (MLO)
      each presented primarily with a fixed mass involving the flat bones of the skull.
      Twenty-five dogs were treated with surgical resection alone, nine were treated
      with adjuvant therapy, and five were not treated. Forty-seven percent of dogs
      treated had local tumor recurrence, and 56% had metastasis. Median time to
      recurrence, median time to metastasis, and median survival time were 797, 542,
      and 797 days, respectively. Histological grade, surgical margins, and tumor
      location affected outcome. Long-term remission can be obtained with aggressive
      treatment of MLO, although it is locally invasive and moderately metastatic.

PMID- 9527426
TI  - Extraskeletal osteosarcomas in dogs: 14 cases.
AB  - Fourteen dogs (11 females, three males) with extraskeletal osteosarcomas (EsOSAs)
      were identified. The median age was 11.5 years. The median body weight was 18 kg.
      The primary sites of the EsOSAs were the spleen (n=6), mammary gland (n=3), lung
      (n=2), and one each in the skin, axilla, and mesenteric root. The overall median
      survival time was 74 days. The only factor which was found to be prognostic for
      survival was the use of chemotherapy (p of 0.02). Cases which did not have
      chemotherapy were 3.62 times as likely to die a tumor-related death than cases
      which had chemotherapy.

PMID- 9527427
TI  - Fibrosarcoma in the distal radius and carpus of a four-year-old Persian.
AB  - A four-year-old Persian was presented for evaluation of a nonweight-bearing, left
      forelimb lameness. Radioulnar and pancarpal osteolysis with minimal periosteal
      reaction were seen on radiographs of the antebrachium. Cytological examinations
      of fine-needle aspirates and impression smears were suggestive of sarcoma. After
      forequarter amputation, histopathological examination provided a diagnosis of
      fibrosarcoma with axillary lymph-node metastasis.

PMID- 9527428
TI  - Isolated right-ventricular hypertrophy associated with severe pulmonary vascular
      apolipoprotein A1-derived amyloidosis in a dog.
AB  - A 12-year-old dachshund was referred for respiratory distress, coughing, and
      weight loss. Cyanosis, dyspnea, tachypnea, and harsh lung sounds were noted on
      physical examination. Polycythemia with an increased number of nucleated red
      blood cells; right atrial enlargement; severe interstitial-to-alveolar pattern in
      all lung fields; and peripheral, echogenic, pulmonary masses were observed.
      Cytological examination of pulmonary aspirates indicated possible pulmonary
      carcinoma. The dog was euthanized at the owner's request. Isolated right
      ventricular hypertrophy and pulmonary arteriopathy with amyloid deposits of
      apolipoprotein A1 were identified upon necropsy and histopathology. Pulmonary
      vascular amyloidosis should be considered in the differential diagnoses of
      respiratory distress in aged dogs.

PMID- 9527429
TI  - The use of enalapril in the treatment of feline hypertrophic cardiomyopathy.
AB  - The clinical response to enalapril in 19 cats with hypertrophic cardiomyopathy
      (HCM) was evaluated retrospectively. Eleven cats were in congestive heart failure
      (CHF) at the time enalapril was prescribed, while only one cat was in CHF when
      the cats were reexamined three-to-six months later. Significant changes in
      cardiac dimensions were identified echocardiographically. No adverse effects on
      blood pressure, serum creatinine, or potassium were noted. Although the
      preliminary data suggests that enalapril is well tolerated and may contribute to
      some improvements in cats with HCM, controlled, prospective studies are needed to
      prove the efficacy of enalapril in this disease.

PMID- 9527430
TI  - Diagnosis of shoulder instability in dogs and cats: a retrospective study.
AB  - The glenohumeral joint is a remarkable articulation providing the greatest range
      of motion of any joint in the body. Glenohumeral stability results from several
      mechanisms, including those that do not require expenditure of energy by muscle
      ("passive mechanisms") and those that do ("active mechanisms"). Glenohumeral
      instability has been recognized in 47 shoulders of 45 dogs and one cat. Cases are
      presented because of chronic foreleg lameness. Shoulder joint pain is obviated by
      the orthopedic examination. Only 57% of the involved shoulders presented with
      degenerative joint disease. Signs of instability are recognized under anesthesia
      using a craniocaudal or mediolateral drawer sign or both. This report describes
      the radiographic and arthroscopic findings of shoulder instability. Arthroscopy
      of the shoulder joint allows identification of all intra-articular pathologies.
      Shoulder instability, not fully recognized in the past, appears to be the most
      common cause of shoulder lameness in the dog.

PMID- 9527432
TI  - Influence of thoracic conformation and genetics on the risk of gastric dilatation
      volvulus in Irish setters.
AB  - Body measurements, history of gastric dilatation-volvulus (GDV), and other data
      were obtained for 155 Irish setters at the 1994 National Specialty Show. The dogs
      ranged in age from 6.5 months to 12.4 years (mean+/-standard deviation [SD],
      3.6+/-2.6 years); 11 (7%) of the dogs had histories of GDV. Gastric dilatation
      volvulus risk increased 33% for each year of age (p of 0.01). Dogs with the
      deepest thorax relative to width (ratio range, 1.61 to 1.85) had a significantly
      greater GDV risk than those with the shallowest thorax (ratio range, 1.20 to
      1.50); the odds ratio was 8.45; the 95% confidence limits were 1.44 to 49.57; and
      the p value equaled 0.02. Having a relative (particularly a parent) with GDV also
      increased GDV risk. Five-generation pedigrees yielded a significantly higher mean
      coefficient of relationship for the 11 dogs with GDV than for the 11 dogs without
      GDV.

PMID- 9527431
TI  - The canine intervertebral disk: part one: structure and function.
AB  - Intervertebral disk disease continues to be a common and debilitating condition
      of dogs. In the first of a two-part article on the canine intervertebral disk,
      the microscopic and ultrastructural anatomy of the normal, nonchondrodystrophoid
      disk is described. Specific attention is placed on elements of the structure
      which impart important functional attributes. Finally, the role of the
      intervertebral disk in providing flexibility to the vertebral column is
      discussed, with a description of its biomechanical properties and reaction to
      compressive loads.

PMID- 9527434
TI  - The fluctuation of tear production in the dog.
AB  - The fluctuation and variation in canine tear production were established by
      evaluating the results of daily Schirmer tear test I (STT I) and weekly STT I and
      Schirmer tear test II (STT II) conducted on healthy dogs. The objectives of the
      study were to determine the fluctuation in STT values in dogs and its
      significance on both a daily and weekly basis; to determine the magnitude of the
      measured differences; and to identify any factors that might influence the
      fluctuation in STT values or variations of normal values between different dogs.
      The results of the study indicate that fluctuations in the STT values occur on
      both a daily and weekly basis. The fluctuations were only biologically
      significant on a week-to-week basis. There are significant differences between
      STT I and STT II values in dogs. The results also indicate that weight has a
      significant effect on STT values, with higher values measured in dogs of
      increasing body weight.

PMID- 9527433
TI  - Physaloptera infection in 18 dogs with intermittent vomiting.
AB  - Physaloptera infections were diagnosed endoscopically in 18 dogs. Each case had
      vomiting as the primary clinical sign, and four cases had regurgitation as a
      concurrent sign. Fecal flotations, using magnesium sulfate solution, were
      performed in 12 of the 18 cases and were negative for Physaloptera eggs. In 12 of
      the 18 cases, only one worm was seen during endoscopic examination. Fifteen of 18
      cases were treated with pyrantel pamoate, and 10 of 12 cases with follow-up had
      resolution of their vomiting.

PMID- 9527436
TI  - Drug information reaching more patients, FDA data show.

PMID- 9527435
TI  - The use of propofol as an induction agent for halothane and isoflurane anesthesia
      in dogs.
AB  - Cardiovascular, pulmonary, and quantitative electroencephalographic parameters
      were assessed in 12 anesthetized dogs to determine the compatibility of the
      injectable anesthetic propofol with halothane and isoflurane. No cases of apnea
      were observed during induction of anesthesia. An adequate level of anesthesia was
      established in each protocol as judged by both the lack of response to mechanical
      noxious stimuli (i.e., tail clamping) and evidence of reduction in total
      amplitude of brain wave activity. The initial propofol-mediated decrease in
      arterial blood pressure continued during either halothane (52.4%) or isoflurane
      (38%) anesthesia without a simultaneous increase in heart rate. The results of
      this study suggest that propofol, in combination with inhalant agents, can be
      used effectively and safely for canine anesthesia in veterinary practice.

PMID- 9527437
TI  - Comanagement: a word used to hide collusion.

PMID- 9527438
TI  - Comanagement: a word used to hide collusion.

PMID- 9527439
TI  - Environmental dermatology. Festschrift for H.R.H. Crown Prince El-Hassan bin
      Talal.

PMID- 9527440
TI  - Allergy to cocamide DEA.
AB  - Three cases are reported of individuals allergic to cocamide DEA, also known as
      coconut diethanolamide. In two cases, multiple other cutaneous allergies were
      present. In both instances, cocamide DEA was present in several personal care
      products used by the patients. In the third case, occupational exposure was
      suspected. Cocamide DEA is an unusual allergen that may cause contact dermatitis
      in individuals who often have multiple other skin allergies.

PMID- 9527441
TI  - Synthesis of ginsenoside Rg3, a minor constituent of Ginseng radix.
AB  - Glycosylation of 12beta-acetoxy-dammar-24-en-3beta,20(S)-diol (4), with hepta-O
      acetyl-alpha-sophorosyl bromide (5) under catalysis by Ag2CO3 or Ag2O afforded a
      chromatographically unseparated mixture of the alpha- and beta-linked
      octaacetates 6 and 7 in an approximately 2.5:1 ratio. After deprotection and
      chromatographic purification, the free alpha- (8) and beta-glycosides (9) were
      obtained. Sophoroside 9 was identical in all respects with ginsenoside Rg3, the
      minor component of Ginseng Radix rubra. All compounds were fully characterized by
      1H and 13C NMR spectroscopy.

PMID- 9527444
TI  - Inactivation of alpha-ketoglutarate dehydrogenase during its enzymatic reaction.
AB  - The activity of some muscle alpha-ketoglutarate dehydrogenase complexes (KGDC)
      decreases during their enzymatic reaction as a result of inactivation of the
      first component of the complex, namely, alpha-ketoglutarate dehydrogenase (KGD).
      This decrease is associated with transformation of the complex produced by KGD
      and alpha-keto substrate in the course of oxidative phosphorylation. Kinetics of
      KGD inactivation during the reaction depends on teh keto substrate structure.
      When alpha-ketoglutarate (KG) is used as a substrate, KGD inactivation occurs in
      two stages. The major (irreversible) decrease in its activity is observed during
      the first minutes of reaction. During reaction with a catalytically active KG
      analog, alpha-ketoadipate (KA), the enzyme is irreversibly inactivated in one
      stage. This suggests that the reversible stage of inactivation is due to the high
      rate of catalysis, which is characteristic of KG-utilizing reactions. Decrease in
      the rate of KG oxidation after treatment of the enzyme with sulfhydryl reagents
      eliminates this reversible stage. Preincubation of KGD with KG phospho
      derivatives (succinylphosphonate or its monomethyl ether) changes the properties
      of KGD in a similar way to the reversible decrease of activity during catalysis.
      The arginine residue of KGD, which is essential for enzymatic activity, becomes
      inaccessible for butanedione in the complexes of KGD with some phospho
      derivatives. The data suggest that the reversible inactivation of KGD in the
      course of catalysis is due to an interaction of the leaving substrate carboxyl
      with the essential arginine residue of the enzyme.

PMID- 9527442
TI  - Orexins and orexin receptors: a family of hypothalamic neuropeptides and G
      protein-coupled receptors that regulate feeding behavior.

PMID- 9527445
TI  - [Drug therapy--legal limits of prescription writing. Proceedings of the 20th
      Symposium for Jurists and Physicians. Berlin, Germany, 14-15 February 1997].

PMID- 9527443
TI  - Inhibition of pigeon breast muscle alpha-ketoglutarate dehydrogenase by
      structural analogs of alpha-ketoglutarate.
AB  - Inhibition of alpha-ketoglutarate dehydrogenase (KGD) by dicarboxylates with
      (oxaloacetate and ketomalonate) and without (malonate, succinate, and glutarate)
      alpha-keto group was studied. Ketodicarboxylates at low concentrations inhibit
      KGD in competitive manner. Increase in their concentrations results in appearance
      of the noncompetitive component. The extent of KGD inhibition by keto
      dicarboxylates increases with structural similarity of the inhibitor and the
      substrate, irrespective of preliminary incubation of the enzyme with the
      inhibitor. This is indicative of blocking the substrate-binding site of KGD by
      dicarboxylates. In contrast, inhibitory effect of dicarboxylates which contain no
      keto group increases as their structural similarity with the substrate decreases.
      Saturation of KGD with dicarboxylates of this type does not completely suppress
      the enzymatic activity. Alternatively, these analogs display competitive mode of
      inhibition. Analysis of the data obtained suggests that these dicarboxylates
      produce catalytically active triple complex keto substrate-KGD-dicarboxylate and
      that KGD which enters the composition of such a complex inhibits a decreased
      affinity for the keto substrate as a result of the inhibitor binding.

PMID- 9527446
TI  - [Therapeutic freedom of the physician].
AB  - The therapeutic freedom of choice is one of the main elements of the medical
      profession. It is fought for by two competing powers: the patient's will on the
      one hand, and the reasons of welfare state on the other. A threatened fundamental
      maxim is at stake, which the characteristic of the medical profession depends on
      essentially. Its content is to be illustrated and showed clearly in the context
      of greater interrelations and reciprocity.

PMID- 9527447
TI  - [National and European drug approval procedures].
AB  - On the basis of national and European regulations, different authorization
      procedures exist side by side in Germany. There are the national procedures
      governed by the German drug law, and those directly governed by the guidelines
      and regulations of the European Union. National procedures can be applied to
      drugs with new or with known substances while they are obligatory in the case of
      standard preparations, parallel imports and the so-called old market products.
      Licensing under a national procedure is valid exclusively in Germany. Also the
      decentralised procedure is completed by issuance of a national marketing license.
      Products passing through the centralised procedure of the London drug agency
      (EMEA) are not granted individual national authorizations but European Commission
      issued marketing authorizations; these are simultaneously valid for all members
      States of the European Communities.

PMID- 9527448
TI  - [Approval of drugs by national and European agencies--sequelae for the
      pharmaceutical industry].
AB  - The research-based pharmaceutical industry supports the European harmonization
      process for the granting of pharmaceutical registrations. In order to improve
      consumer protection and the therapeutic options available to physicians in
      comparison to nationally registered products, the harmonization must be carried
      out on schedule and transparently a high scientific standard. It must not lead to
      the adoption of all national restrictions regarding data sheets and patient
      leaflets. Pharmaceutical products with the same ingredients can be registered
      either through the national or through the European procedure. This situation can
      only be remedied by the harmonization of core SPCs. This process must be agreed
      in consultation between pharmaceutical companies and regulatory authorities. With
      regard to measures to avert drug risks, professional associations and the
      pharmaceutical companies affected should be heard by the national authorities and
      their arguments given due consideration. In addition, national authorities and
      the CPMP must coordinate their decisions before they are published. In
      particular, the basis of these decisions should be made clear and therapeutic
      alternatives should be known.

PMID- 9527449
TI  - [Approval of drugs by national and European agencies--from the viewpoint of drug
      approval committee A].
AB  - The German Medicines Act was issued in 1976 (1 1/2 decades after the thalidomide
      tragedy) and intends the installation of a non-governmental commission A,
      recruited of independent external experts, before a new drug is licensed. All
      medical and pharmaceutical disciplines are represented in this non-governmental
      commission A. They are elected and empowered by the minister of health for three
      years. The non-governmental commission A examines independently all applications
      of new drugs. It is part of the licensing process rather than an advisory
      committee. In case the vote of the non-governmental commission A differs from the
      regulatory authority, the latter takes the final decision but has to submit its
      argumentation for the different evaluation. This separation of the competence of
      decision making between the authority and the external experts constitutes a
      novum in the German legislation as well as worldwide. The discussions and votes
      of the non-governmental commission A are confidential. Some experiences on the
      work of the non-governmental commission A are dealt with in more detail.

PMID- 9527450
TI  - [Modification of the prescribing practice of the physician by drug approval
      decisions of federal agencies].

PMID- 9527451
TI  - [Modification of the prescribing practice of the physician by decisions of drug
      committees, specialty groups and consensus conferences].
AB  - The Drug Commission of the Medical Profession influences the prescribing
      behaviour of physicians operating under the National Health Scheme in various
      ways with various grades of obligation: 1. via announcements in the journal of
      the society of physicians of Germany "Deutsches Arzteblatt" with particular focus
      on aspects of drug safety which the German physician to consider according to the
      legal opinion has; 2. via the "therapeutic guidelines" according No. 14 of "the
      guidelines for drug therapy" which the physician operating under the National
      Health Scheme has to take into account; 3. via a "compendium about drug
      prescriptions", edited by members of the Drug Commission listing ca. 800
      recommended drugs from a total of ca. 2600 individual drugs on the national
      market: 4. via other means of via other means of communication such as fax-on
      demand-service or the bulletin "drug prescription in the medical practice" with
      contents of significantly less definite character.

PMID- 9527452
TI  - [Modification of the prescribing practice of the physician by legislation with
      special reference to non-approved drugs].
AB  - Prerequisite for any prescription is the doctor's basic knowledge on the benefits
      and risks of the medicine. Under the obligation to exercise due care, the
      physician may even prescribe non-registered medicines if scientifically
      justified. Exceptionally, the use of a non-registered medicine is even
      imperative.

PMID- 9527454
TI  - [Prerequisites in prescribing practice: physician decision processes].
AB  - Selecting a drug for proper treatment of the patient is still primarily the
      physicians choice. The selection is usually not influenced beforehand but subject
      to control in a case of malpractice. It must be taken into consideration,
      however, that about half of the practising doctors in Germany are working in
      their own practice. The vast majority of these are participating in the statutory
      health insurance system. Their therapeutic measures have to be in accordance with
      the social code, it's by-laws, regulations and guidelines. Drugs may only be
      prescribed if a curable decrease has been determined and the range of potential
      prescriptions has been scrutinised. Two "negative lists" have to be observed. In
      addition to this, the prescription must be effective, sufficient and may not
      exceed the necessities. If there are therapeutic alternatives the drugs efficacy
      must be taken into evaluation. Since the beginning of 1993 the doctor's choice is
      also influenced by the overall budgeting of drug expenses and the fear of
      personal liability for a budget excess.

PMID- 9527453
TI  - [Experiences of the expert committee on questions of prescribing freedom].
AB  - Over a period of 20 years, the Mediation Committee Nordrhein settled more than
      10,000 cases of supposed maltreatment. Only 4.2% of the cases concerned assumed
      faulty medication. In less than one third of them, maltreatment was recognized.
      Exact medical documentation is necessary for a fair and impartial settlement of
      the case.

PMID- 9527455
TI  - [Negative lists and positive lists--health policy aspects].
AB  - Negative- and positive lists are instruments of quality-management in healthcare.
      They help to guarantee a rational and economic therapy of pharmacology. The
      'voluntary positive-list' formulates a professional and scientific valid standard
      for every physician. At the same time it motivates for a permanent discussion
      between colleagues about wise use of remedy. The risks and side-effects of the
      medical market are uncontrollable without such transparent media and help for
      decision.

PMID- 9527456
TI  - [Positive lists/negative lists from the viewpoint of clinical pharmacology].
AB  - Drug lists reduce freedom of choice, but are a logical consequence when drugs are
      prescribed, which are of no proven value. The current prescribing behaviour is
      the consequence of insufficient training in clinical pharmacology in medical
      schools and postgraduate education. Positive lists have shown to be of
      significant value for hospitals in order to reduce the number of drugs available,
      which brings safety advantages for the patient, improves in depth knowledge of
      the physician and reduces stock keeping for the pharmacy.

PMID- 9527457
TI  - [Legal boundaries of negative and positive lists].
AB  - Positive lists comprise only a limited number of medicines destined for
      reimbursement by the health insurance companies. Intentions to publicize those
      lists at federal and provincial levels failed for constitutional reasons.
      Negative lists--on the other hand--as prepared by health insurance companies are
      admissible as long as they are--among other things--open for changes according to
      the scientific progress. Medicines being incorporated into a negative list can be
      prescribed but are not reimbursable.

PMID- 9527458
TI  - [Limited prescribing freedom by federal cost regulation?].
AB  - The governmental budgeting of the overall expenses for medicines obviously does
      not impair the quality of medical treatment. But pharmaco-epidemiologic
      investigations are lacking. This regulation is just an instrument for diminution
      the health care expenses without interfering with the quality of prescription and
      provision of medicines.

PMID- 9527459
TI  - [Limiting prescribing freedom in the hospital].
AB  - The restrictions on the independence of prescriptions in hospitals result from
      the health insurance law and from the legal regulations for the hospital
      finances. Within the hospital, the restrictions on the freedom of prescription
      are laid down by law. Although on the one hand, the head doctor responsible for
      the medical treatment within his ward is independent of any restrictions
      regarding diagnosis and therapy, he is, however, committed to a treatment as
      economical as possible, which creates a field of conflicts that are quite
      frequently very difficult to solve.

PMID- 9527460
TI  - [The physician between cost control and quality requirements].
AB  - In times of reduced monetary resources of the current German health system, it is
      more and more difficult for the German physicians to comply with the high
      medicinal care standard and to practice economically. Nevertheless, the
      economical reasons cannot deny the high medical quality standards. Regarding the
      principle of the unity of jurisdiction, the validity of the social welfare law,
      that a performance has to be "just sufficient and suitable", must concur with the
      demand of liability law of "indication of the medical service". The economical
      duties reach their limit when they increase the risk for the patient. On the
      other hand, the economy interests have to be regarded by the "principle of the
      allowed risk". Therefore, it should be considered that in every single case the
      severity and probability of the risk has to be weighed against the cost aspect.

PMID- 9527461
TI  - [New medical care models in the USA and their effect on the therapeutic freedom
      of the American physician].
AB  - Managed care and quality control have markedly changed American medicine. After
      describing some of the more important features of the recent activities in the
      American health care reform, this article describes the methods used by managed
      care corporations in improving pharmaceutical treatment quality and
      pharmaceutical treatment costs. The advantages of newer methods to improve
      pharmacotherapy (eg. pharmaceutical benefits management) are then balanced
      against their potential dangers (eg. loss of physician autonomy or manipulation
      of drug prescription and consumption by health care corporations).

PMID- 9527463
TI  - [Education responsibility, specialty and administration information from the
      legal viewpoint].
AB  - The producer and the distributor of medicines as well as the physician are
      obliged to inform the patient about risks and side effects of medicines prior to
      use. The pharmaceutic producer must inform the physician through respective data
      sheets and the patient through leaflets inserted in the packages. The value of
      the latter are doubtful and not always useful. In any case written informations
      are not sufficient. The physician after clearing up the individual situation has
      to orally inform the patient taking his intellectual level into account.

PMID- 9527462
TI  - [Patient education responsibility, specialty and administration information from
      the viewpoint of the pharmaceutical industry].
AB  - The provision of detailed information to patients is a complex and multifarious
      process in which the pharmaceutical industry is only partially involved alongside
      the physicians and, where appropriate, the pharmacists. The provision of
      information to patients has three goals: Assuming the patient to be a mature,
      responsible being, the objective is to create circumstances in which he/she is
      capable of taking and or participating in decisions concerning his/her health
      (patient autonomy). The patient should employ medicinal products such that their
      beneficial characteristics achieve the greatest possible effects and their risks
      are confined to a minimum (compliance). The physician's data sheet and, in
      particular, the patient leaflet, are intended to promote the safety of use. This
      means that not only should the drug risks be kept to a minimum but also the risk
      of non-use or of inadequate administration should be anticipated. Should risks or
      damage occur due to incorrect use or even correct use they must be restricted to
      the minimum possible (minimization of damage).

PMID- 9527464
TI  - [Patient education responsibility, specialty and administration information from
      the internal medicine viewpoint].
AB  - Drug therapy requires both the thorough education of the patient by the physician
      and the patient's consent. The contents of the patient education should be based
      on the urgency of drug therapy, the patient's educational background, and his
      level of knowledge. Besides the instructions and explanations given to medicine
      users by physicians or pharmacists, the written patient information leaflet
      represents the main source of information. The objectives of the written
      information concerning a pharmaceutical product are to provide patients with
      clear information about the drug and, thus, to improve the drug compliance.
      Guidelines of the European Community (EC) for the writing of drug information
      leaflets (guideline 92/27) will hopefully lead to a more consumer-oriented drug
      information. The data sheet should give medical specialists the detailed
      information needed to safely use the drug. The note for guidance "Summary of
      Product Characteristics", recently proposed by the CPMP (Committee for
      Proprietary Medicinal Products) of the EC, provides detailed instructions on how
      to present drug information.

PMID- 9527465
TI  - [Patient education and specialty prescription information from the psychiatric
      viewpoint].

PMID- 9527466
TI  - [Special therapeutic guidelines from the viewpoint of BfArM (Federal Institute
      for Drug and Medical Products)].
AB  - Homeopathic, anthroposophic and phytotherapeutic drugs are subject to the German
      Medicines Act of 1976 (AMG). The relevant EU regulations also refer to this group
      of medicinal products. Definitions and requirements for proof of adequate
      quality, efficacy and safety are set out by regulations under national law, as
      well as EU and WHO regulations. Homeopathic products may be registered without
      statement of indication. It has become possible in the meantime that medicinal
      products belonging to these particular schools of therapy and groups of
      substances are critically reviewed and assessed without being blamed for bias in
      the sense of discrimination against one of these therapies or exaggerated
      criticism. The term of "particular schools of therapy and groups of substances"
      is different from what is understood by "traditional" products according to
      article 109a AMG. "Traditional" products are subject to reduced requirements and
      their documentation need not fulfil the assessment criteria established for
      particular schools of therapy.

PMID- 9527467
TI  - [Special therapeutic practices from the viewpoint of naturopathy].
AB  - Naturopathy being orientated towards natural science and conventional medicine
      does not lead to basically different judgements about unconventional treatments
      nor about special therapies such as homeopathy, phytotherapy or anthroposophic
      medicine. It may, however, be more open-minded towards new ideas and theoretical
      even philosophical concepts and it is more likely used to question the 'state of
      the art' of actual medical knowledge. It is only for a relatively small part of
      unconventional treatments, that naturopathy recognizes a certain plausibility,
      which causes scientific investigation of the method to be meaningful. Naturopathy
      sometimes proposes traditional anthropologies and nosologies to be used for the
      election of suitable indications. A variety of psychologic effects of different
      methods of naturopathy may not be excluded by protocols used for clinical
      studies. As far as the majority of unconventional and paramedical treatments is
      concerned, naturopathy raises ethical beside scientific objections. Beyond a
      probable success of the treatment, it insists on a certain rationale and
      intellectual honesty. A differentiation between the more pragmatic interests of a
      health insurance and the scientific obligations of university medicine is given.
      An important and decisive criterium for the health insurances results from the
      demand for economics.

PMID- 9527468
TI  - [Special therapeutic processes from the viewpoint of clinical pharmacology].
AB  - Special therapies comprise homeopathic drugs, anthroposophic medicine and
      phytotherapy a heterogenous mixture, which consists partly on authorities
      (Hahnemann, Steiner) and partly describes the origin of the drug (herbal drugs).
      The field, therefore, is open to new additions (Chinese traditional medicine,
      American Indian drug therapy etc.). These drugs do not meet the requirements for
      safety and efficacy required for modern drugs and this is not required, because
      according to German lawyers this would be inadequate. We demonstrate examples
      where the health of patients has been severely damaged by this kind of medical
      therapies and point out that these problems continue. Reasons are presented, why
      the public has the right to demand proof of efficacy and safety of all drugs.

PMID- 9527469
TI  - [Special therapeutic processes from the viewpoint of the lawyer].
AB  - The particular schools of therapy never have been exactly defined--neither by law
      nor by judicature. Despite being in contrast to the scientifically based
      classical medicine, its application is basically accepted by the judicature
      within the general scope of the therapeutic autonomy of the physician. There are
      however, special limitations to be observed by the naturopath in order to protect
      the patient. Thus, disciples of alternative schools of therapy must always
      consider carefully whether or not methods of the classical medicine should be
      preferred for the sake of the patient's health. In addition, they must inform the
      patient about all therapeutic alternatives. Special problems may arise if parents
      reject proven measures of the classical medicine to be applied to their minor
      children. In such a case the child's benefit has priority to the parent's rights.

PMID- 9527470
TI  - [Therapeutic trial, clinical research and therapeutic freedom--medical aspects].
AB  - In the history of medicine, the approach has changed from prevention to curative
      medicine- hand in hand with the availability of the pharmacologic findings. Prior
      to the era of a medicine based on natural science, drugs were found by an
      empirical trial- and error approach resulting in a steadily growing of drugs.
      With the upcoming natural sciences, medicine reached new levels in drug treatment
      by extensive and systematic research in experimental and clinical trials. For
      scientific and regulatory acceptance, national and international guidelines and
      the rules of "Good Clinical Practice" have to be met. On the basis of the respect
      for the "Oath of Hippocrates", the commitment to "salus aegroti suprema lex", the
      responsibility of "nil nocere" and the duty of information are elementary. The
      regulations of the "social legislation" define rights and duties of patients and
      physicians. In spite of all these rules, the physicians' autonomy is undeniable
      because of individualism of patients in contrast to the clinical trials based on
      national and international guidelines.

PMID- 9527471
TI  - [Therapeutic trial, clinical research and therapy freedom--viewpoint of the
      ethics committee].
AB  - The necessity to define the above-mentioned terms is due to the fact that legal
      and administrative regulations pertaining to them are different. To decide on the
      still ambiguous position of studies to optimize therapy seems desirable.

PMID- 9527472
TI  - [Therapeutic trial, clinical research and therapeutic freedom--legal boundaries].
AB  - Clinical research can be therapeutic or purely scientific. The therapeutic trial
      is usually chosen to obtain treatment liberty. On the other hand, the physicians
      in controlled clinical trials have relatively little choice of treatments. In
      Germany, special statutes and the general law limit clinical trials. The sec. 41
      AMG, 18 MPG allow therapeutical trials under special circumstances. There are
      requirements for clinically controlled trials, especially the provision to seek
      the approval of an ethic commission.

PMID- 9527473
TI  - NMR structural characterization of oligo-N-substituted glycine lead compounds
      from a combinatorial library.
AB  - Synthesis and screening of combinatorial libraries for pharmaceutical lead
      discovery is a rapidly expanding field. Oligo-N-substituted glycines (NSGs) were
      one of the earliest sources of molecular diversity in combinatorial libraries. In
      one of the first demonstrations of the power of combinatorial chemistry, two NSG
      trimers, CHIR-2279 and CHIR-4531, were identified as nM ligands for two 7
      transmembrane G-protein-coupled receptors. The NMR characterization of these two
      lead compounds was undertaken to verify covalent connectivity and to determine
      solution conformations, if any. The sequential chemical shift assignments were
      performed using a new strategy for assigning 1H and 13C resonances of NSGs. The
      conformational preferences were then determined in both an aqueous co-solvent
      system and an organic solvent to probe the effects of hydrophobic collapse. NSGs
      are expected to be more flexible than peptides due to the tertiary amide, with
      both cis and trans amide bond conformations being accessible. Solution NMR
      studies indicate that although CHIR-2279 and CHIR-4531 have identical backbones
      and termini, and very similar side chains, they do not display the same solution
      conformational characteristics.

PMID- 9527474
TI  - Peptomers: a versatile approach for the preparation of diverse combinatorial
      peptidomimetic bead libraries.
AB  - This report describes a versatile approach in the generation of peptidomimetic
      bead libraries. The method is based on the preparation of peptide-peptoid hybrids
      using the portioning-mixing procedure, which gives diverse peptidomimetic bead
      libraries composed of peptides, peptoids and peptide-peptoid hybrids. We term
      these peptomers, from peptide-peptoid hybrid polymers. The synthesis of the
      peptomers is easily accomplished by adapting the peptoid synthesis strategy, in
      which a primary amine reacts with bromoacetic acid, and we combine this
      methodology with conventional peptide synthesis. The sequence of the active
      compound is deduced by conventional microsequencing using Edman degradation
      chemistry, thus avoiding the synthesis of a coding structure or the addition of
      molecular tags. We demonstrate the utility of the peptomer approach by the
      synthesis of a bead library together with the identification of novel
      peptidomimetic ligands binding to the macromolecular targets streptavidin and the
      insulin receptor.

PMID- 9527475
TI  - Composition and purity of combinatorial aryl ether collections analyzed by
      electrospray mass spectrometry.
AB  - Electrospray mass spectrometry (ESI-MS), tandem mass spectrometry and on-line RP
      HPLC-ESI-MS were used to evaluate the composition and purity of three different
      aryl ether mixtures consisting of 10 and 45 aryl ethers synthesized on solid
      support by Williamson etherification. The libraries feature two potential
      pharmacophores connected with three different spacers and serve as models for a
      detailed component analysis. Individual members of the library and by-products
      were identified rapidly and conveniently by product ion scans. Compound
      collections obtained by two different synthetic methods, the split/combine
      approach and the premix method, showed different mass distributions in the ESI-MS
      spectra. Some components were not detected in direct ESI-MS measurements, but
      were found by MS/MS experiments. Precursor ion and constant neutral loss scans
      allowed the identification of components with common structural features.

PMID- 9527476
TI  - Limitations of the coupling of amino acid mixtures for the preparation of
      equimolar peptide libraries.
AB  - The standard method of peptide library synthesis involves coupling steps in which
      a single amino acid is reacted with a mixture of resin-bound amino acids. The
      more recently described positional scanning strategy (in which each position in
      the peptide sequence is occupied in turn by a single residue) is different since
      it involves the coupling of mixtures of amino acids to mixtures of resin-bound
      amino acids. In the present study, we analyze the compounds produced under these
      conditions measuring coupling rates and amounts of formed products, using mainly
      UV, HPLC, LC/MS and MS/MS techniques. Our data do not permit to conclude that the
      resulting libraries are complete. Indeed, our analytical data indicate that a
      large part of the di-, tri- and tetrapeptides synthesized with this method are
      not present in the final mixture. Although chemical compensation (in which poor
      coupling kinetics is compensated by a larger excess of the incoming amino acid)
      has been thought to counterbalance these biases, our experiments show that the
      compensation method does not take into account the crucial influence of the resin
      bound amino acid and that even the dipeptide libraries obtained in this way are
      far from completeness. The present work provides strong evidence that the
      coupling of mixtures of amino acids to resin-bound residues, which is required by
      the positional scanning strategy, results in incomplete and/or non-equimolar
      libraries. It also clearly confirms that coupling rates in solid-phase peptide
      synthesis are dependent on the nature of both the incoming and the immobilized
      amino acid.

PMID- 9527477
TI  - High throughput analysis and purification in support of automated parallel
      synthesis.
AB  - Rapid reverse-phase analytical and preparative HPLC methods have been developed
      for application to parallel synthesis libraries. Gradient methods, short columns,
      and high flow rates allow analysis of over 300 compounds per day on a single
      system, or purification of up to 200 compounds per day on a single preparative
      system. Hardware and software modifications allow continuous unattended use for
      maximum efficiency and throughput.

PMID- 9527478
TI  - High-resolution density gradient electrophoresis of proteins and subcellular
      organelles.
AB  - Following a concept developed by Bier et al. (Electrophoresis 1993, 14, 1011
      1018), binary mixtures of amphoteric buffers with low conductivity and a good
      buffering capacity permit rapid rate zonal separation of proteins on a density
      gradient electrophoresis apparatus (7 cm, x 2.2 cm). At pH 8.66 and 250 V, beta
      lactoglobulin (Mr 36600) was separated into the A and B isoforms within 44 min;
      human transferrin (Mr 76000-81000) was separated into its sialylated glycoforms
      and carbonic anhydrase (Mr 30000) separated into its isoenzymes. From these
      results we arrive at the term high-performance density gradient electrophoresis.
      Compartments belonging to the endosomal system were separated by density gradient
      electrophoresis. Early endosomes, recycling vesicles, intermediate endosomes,
      late endosomes and lysomes became well-separated after 80 min at 10 mA using
      [125I]transferrin and horseradish peroxidase as reporter molecules in pulse-chase
      regimes. Mixtures of Bier buffers and standard electrophoresis media permitted
      very short separation times (19 min at 10 mA) for the endosomal compartments.
      Concommittantly, endoplasmic reticulum and proteasomes were well resolved.

PMID- 9527479
TI  - Free-flow electrophoretic analysis of endosome subpopulations of rat hepatocytes.
AB  - The separation of functional early and late endosomes from other cellular
      compartments by free-flow electrophoresis (FFE) has been previously demonstrated
      in nonpolarized cells. Here, using 125I-labeled anti-secretory component
      antibodies ([125I]SC Ab) and FITC-labeled asialoorosomucoid (FITC-ASOR) as
      markers of the transcytotic and lysosomal pathway, respectively, we demonstrate
      the separation of three distinct endosome subpopulations from polarized rat
      hepatocytes. Internalization of both markers at 16 degrees C resulted in their
      accumulation in a common endosome compartment, indicating that both the
      transcytotic and the lysosomal pathways are arrested in the sorting early
      endosome at temperatures below 20 degrees C. After chase of the markers from
      early endosomes into the transcytotic or the degradative route at 37 degrees C,
      transcytotic endosomes carrying [125I]SC Ab migrated with an electrophoretic
      motility between early and late endosomes while late endosomes labeled with FITC
      ASOR were deflected more towards the anode than early endosomes. These data
      indicate that in rat hepatocytes, the transcytotic and lysosomal pathways utilize
      a common (i.e. early endosomes) and two distinct endosome subpopulations (i.e.
      transcytotic endosomes, late endosomes) prior to delivering proteins for biliary
      secretion or lysosomal degradation, respectively.

PMID- 9527481
TI  - Use of free-flow electrophoresis for the analysis of cellular uptake of
      picornaviruses.
AB  - Free-flow electrophoresis is a powerful tool to separate subcellular vesicles
      such as early and late endosomes from plasma membranes. Using this technique, the
      intracellular distribution of poliovirus type 2 Sabin (PV2) and its derived
      subviral particles was analyzed upon infection of HeLa cells. Comparison of
      various infection conditions showed that maximally 30% of total cell associated
      PV2 was found in endosomal compartments with the remainder being associated with
      plasma membrane fractions; 2% of viral label was recovered from the cytoplasm in
      form of free virions. Sucrose gradient centrifugation analysis of the viral
      material recovered from the respective fractions revealed that intracellular
      virus was exclusively in its native conformation. This is in sharp contrast to
      human rhinovirus serotype 2 (HRV2), which is rapidly modified to RNA-free
      subviral particles upon accumulation in endosomes. The data suggest that
      productive poliovirus uncoating can occur at the plasma membrane whereas
      internalized virus is most probably aborted.

PMID- 9527480
TI  - Analysis of subcellular organelles involved in major histocompatibility complex
      (MHC) class II-restricted antigen presentation by electrophoresis.
AB  - Presentation of material derived from pathogenic organisms to the immune system
      requires uptake of antigens into antigen presenting cells, processing into
      peptide fragments and loading of the resulting fragments onto major
      histocompatibility complex (MHC) class II molecules. MHC class II-restricted
      antigen presentation involves both the biosynthetic as well as the endocytic
      pathway of antigen-presenting cells. In recent years, the general mechanisms that
      govern these processes have been delineated, and specialized organelles have been
      characterized in which processing and loading of antigens takes place. Here, we
      review the work that has led to the characterization of these MHC class II
      compartments, and describe the use of organelle electrophoresis and two
      dimensional gel electrophoresis to analyze the molecular composition of the
      different subcellular organelles involved in MHC class II-restricted antigen
      presentation as well as in antigen uptake.

PMID- 9527482
TI  - Rab proteins and post-Golgi trafficking of rhodopsin in photoreceptor cells.
AB  - Polarized sorting of rhodopsin in retinal rod photoreceptors is mediated by post
      Golgi vesicles that bud from the trans-Golgi network and fuse with the
      specialized domain of the plasma membrane in the rod inner segment. This domain
      surrounds the cilium that connects the inner segment and the rod outer segment to
      which mature rhodopsin is delivered. To dissect the sorting machinery that
      regulates budding, targeting, and fusion of rhodopsin carrier vesicles, their GTP
      binding protein composition has been studied using multiple means including high
      resolution two-dimensional gel electrophoresis and [32P]GTP overlays of renatured
      proteins. These studies indicate a succession on rhodopsin-bearing vesicles of
      rab6, rab11, rab3 and rab8, all members of the small GTP-binding protein family
      of the known regulators of membrane trafficking. In this review the role of rab
      proteins in post-Golgi trafficking of rhodopsin is discussed.

PMID- 9527483
TI  - Mycobacterial phagosome maturation, rab proteins, and intracellular trafficking.
AB  - One of the most prominent features of pathogenic mycobacteria, which include the
      potent human pathogens Mycobacterium tuberculosis and Mycobacterium leprae and
      their opportunistic relatives Mycobacterium avium and Mycobacterium marinum, is
      their ability to survive and multiply in phagosomes of mononuclear phagocytic
      cells. The phagocytosed mycobacteria reside in a vacuolar compartment which is
      exempted from maturation into the phagolysosome. Recently, the arrest of the
      maturation of phagosomes containing M. tuberculosis complex organisms
      (Mycobacterium bovis BCG) has been linked to the accumulation on the phagosomal
      membrane of the small GTP binding protein rab5, specific for the control of
      fusion within the early endosomal compartment. Furthermore, M. bovis BCG
      phagosome is devoid of rab7, a rab protein associated with the late endosome. The
      selective accumulation of rab5 and exclusion of rab7 defines the check point that
      has been compromised in mycobacterial phagosome maturation. Here we summarize
      these observations and relates them to other phenomena in the area of membrane
      and protein trafficking with the emphasis on phagosomes containing intracellular
      pathogens.

PMID- 9527484
TI  - Membrane transport in rat liver endocytic pathways: preparation, biochemical
      properties and functional roles of hepatic endosomes.
AB  - The endocytic compartment has emerged as a major regulator of the uptake and
      processing of circulating ligands, and has been extensively studied during the
      last decade. In this work, the polypeptides of the three endosomal fractions:
      compartment of uncoupling receptors and ligands (CURL), multivesicular bodies
      (MVB) and receptor recycling compartment (RRC), isolated from livers of estradiol
      treated rats, were analyzed by two-dimensional gel electrophoresis. Silver
      stained gels revealed that although the three endosomal fractions shared a
      generally similar pattern of approximately 120 components, qualitative and
      quantitative differences between the three endocytic fractions could be
      demonstrated. The polypeptide composition of the bile was also studied and
      compared with ligands and proteins identified in the different endosomal
      fractions. One- and two-dimensional gel electrophoresis and Western blotting were
      used to investigate the protein composition of the three isolated endocytic
      fractions and 39 proteins were identified. The distribution of identified
      receptors, ligands and structural proteins among the three endosomal fractions
      was in agreement with their expected functionalities and with the different
      endocytic pathways in the hepatocyte.

PMID- 9527485
TI  - The interaction between Mycobacterium and the macrophage analyzed by two
      dimensional polyacrylamide gel electrophoresis.
AB  - The intramacrophage pathogen Mycobacterium avium resides in a vacuole which
      displays unusual fusion characteristics, expressed as both a failure to mature
      into phagolysosomes and a continued access to the early recycling pathway. In
      contrast, compartments containing inert IgG-opsonized latex beads mature to
      phagolysosomes. Techniques were developed for the isolation of these particle
      containing phagosomes from macrophages to facilitate analysis of phagosomal
      constituents by electrophoresis and autoradiography. Metabolic labeling of
      macrophages followed by phagosome isolation and two-dimensional polyacrylamide
      gel electrophoresis revealed only minor differences in the protein profiles
      between the M. avium and IgG-bead phagosomes despite the marked differences in
      the fusigenicity of the respective vacuoles. Pulse-chase labeling experiments
      revealed greater differences in the accessibility of Mycobacterium avium and IgG
      bead phagosomes to newly synthesized proteins. These phagosome isolation
      techniques were extended to analyze the protein synthesis profile of
      intracellular M. avium for comparison with bacteria that were metabolically
      labeled in broth culture. Not surprisingly, the majority of polypeptides in the
      bacilli were common to both growth conditions. However, despite these
      similarities, intracellular M. avium express several unique proteins, most
      notably one abundant protein with a molecular weight of 51 kDa. In addition, the
      bacteria manifest a restricted set of proteins expressed while in stasis shortly
      after infection.

PMID- 9527486
TI  - Two-dimensional gel electrophoresis analysis of endovacuolar organelles.
AB  - Cells perform their multiple functions with the aid of a series of distinct
      membrane organelles. In the last years, many of these compartments have been
      isolated, purified, and extensively studied. The major roles of each organelle in
      the cell are well understood. However, most of the molecular basis by which they
      perform their functions is poorly known. The recent identification and study of a
      handful of proteins associated with endovacuolar compartments has had a major
      impact on the understanding of the molecular details of organelle functions even
      though two-dimensional (2-D) gel analysis indicates that hundreds of proteins are
      typically associated with a complex organelle. This shows that many details and
      surprises are still to come for cell biologists. In the present study, we have
      analyzed and compared different organelles of the endocytic and phagocytic
      apparatus using 2-D gel electrophoresis.

PMID- 9527487
TI  - Preparative two-dimensional gel electrophoresis of membrane proteins.
AB  - Electrophoretic techniques, and especially two-dimensional gel electrophoresis (2
      DE), have provided an indispensable set of tools for the separation of complex
      protein mixtures as well as for the identification of protein-protein
      interactions. Nevertheless, after its introduction more than twenty years ago and
      even with recent technical developments, the separation of integral and
      peripheral membrane proteins, in amounts sufficient for microsequencing, is still
      a difficult task. Lipids present in the membrane as well as the low solubility of
      hydrophobic membrane proteins result in protein aggregation both on the sample
      application point and on isoelectric focusing. As a consequence many proteins do
      not enter the first or second dimension of 2-DE. Here we describe the
      modification of a protocol using a combination of 3-[(3-cholamidopropyl)
      dimethylammonio]-1-propane sulfonate (CHAPS), chaotropic agents (thiourea, urea),
      Tris base and reducing agents (1,4-dithioerythritol) to improve solubilization of
      integral and peripheral membrane proteins. Preparative amounts of membrane
      proteins (up to 2 mg) were loaded during reswelling of dry immobilized pH
      gradients and the resulting Coomassie staining patterns were largely
      superimposable with silver-stained gels obtained from identical samples (4
      microg). This indicates that the recovery of proteins from the sample is not
      significantly compromised by the scale-up procedure. A direct application of this
      method for the characterization and identification of membrane proteins from
      cellular organelles is described in another paper in this issue (I. Fialka et
      al., Electrophoresis 1997, 18, 2582-2590).

PMID- 9527488
TI  - Subcellular fractionation of polarized epithelial cells and identification of
      organelle-specific proteins by two-dimensional gel electrophoresis.
AB  - Protein targeting and sorting is accomplished by complex vesicular transport
      processes that are tightly regulated within a cell. This is especially important
      for epithelial cells because correct delivery of newly synthesized proteins as
      well as recycling and sorting of internalized membrane proteins is essential for
      the establishment and preservation of cellular polarity. Many transport events,
      linking various subcellular compartments, have been analyzed, but many transport
      mechanisms still remain unresolved. In this study we attempted to identify
      proteins specifically associated with distinct organelles in murine mammary
      epithelial cells (EpH4). We isolated subcellular compartments by continuous
      sucrose gradient centrifugation in order to further analyze their protein
      composition by high-resolution two-dimensional gel electrophoresis (2-DE). The
      successful separation of late endosomes (LE), early endosomes (EE) and most of
      the rough endoplasmic reticulum (RER) was confirmed by subsequent analysis of
      gradient fractions for compartment-specific enzymes and marker proteins. Both
      Golgi and plasma membrane (PM) were found to partially co-purify with EE in such
      gradients. Characteristic polypeptide patterns were revealed on 2-DE gels for
      fractions enriched in membranes of different origin. Based on improved sample
      preparation and loading techniques (this issue, C. Pasquali et al.,
      Electrophoresis, 1997, 18, 2573-2581), we were able to identify several proteins
      by immunoblotting or microsequencing of Coomassie-stained spots. This will be the
      basis for a further characterization of organelle-specific molecules in
      epithelial cells as well as for the establishment of a 2-DE reference map of
      membrane proteins from murine mammary epithelium.

PMID- 9527489
TI  - Identification of components of trans-Golgi network-derived transport vesicles
      and detergent-insoluble complexes by nanoelectrospray tandem mass spectrometry.
AB  - Epithelial cells have to deliver newly synthesized proteins to the apical and the
      basolateral plasma membrane domains of the polarized cell surface. Sorting takes
      place in the trans-Golgi network and at least two vesicular carriers exist for
      apical and basolateral delivery. After immuno-isolation, the composition of these
      vesicle preparations was analyzed by two-dimensional (2-D) gel electrophoresis
      and detergent extraction. In this paper we compare the constituents of detergent
      insoluble complexes in different cell lines of polarized or nonpolarized origin
      and present the identification of five previously uncharacterized proteins. We
      show that our protein identification strategy can be successfully applied to the
      problem of small hydrophobic proteins from organisms that have not been
      substantially sequenced. The high sensitivity of nanoelectrospray tandem mass
      spectrometry allowed us to identify two proteins that belong to the p23/p24
      family of putative cargo receptors for vesicular trafficking. Furthermore we have
      mapped CD9 and CD81, two members of a large family of proteins consisting of
      highly hydrophobic four transmembrane proteins. In addition we have identified
      caveolin-2 as a constituent of basolateral transport vesicles. We have also
      extended our analysis of immuno-isolated vesicles to a more basic pI range and
      show that this region on 2-D gels is devoid of proteins. With these approaches
      and with the previously published data we have now identified most of the major
      low molecular weight proteins recovered in detergent-insoluble glycolipid
      enriched complexes.

PMID- 9527491
TI  - Mapping the protein composition of trans-Golgi network (TGN)-derived carrier
      vesicles from polarized MDCK cells.
AB  - In polarized MDCK cells, proteins and lipids are sorted in the trans-Golgi
      network /TGN) and packaged into different vesicular carriers that are delivered
      to the apical or basolateral cell surface. To gain insight into the sorting and
      trafficking machinery, we have previously isolated TGN-derived carrier vesicles
      from perforated MDCK cells. The composition of immuno-isolated apical and
      basolateral carriers was mapped by two-dimensional (2-D) gel electrophoresis.
      Here we describe the identification of several components of the vesicle fraction
      by using three different methods. 2-D gel comigration was performed with carrier
      vesicles isolated from metabolically labeled MDCK cells and human epidermal
      keratinocyte lysates. This allowed us to assign eleven known components by a
      comparison with the comprehensive keratinocyte 2-D gel database. These comprised
      two members of the 14-3-3 family of proteins that have been implicated in
      vesicular trafficking. Five proteins were purified from preparative 2-D gels and
      identified by peptide microsequencing, including the beta1 and beta2 subunit of
      trimeric G proteins and an annexin II variant. A member of the SNARE family of
      proteins was identified by immunoblotting. The combination of 2-D gel
      electrophoresis and 2-D gel databases allows the rapid assessment of the purity
      of subcellular fractions and to characterize components involved in vesicular
      transport.

PMID- 9527490
TI  - Two-dimensional mapping of the endogenous proteins of the rat hepatocyte Golgi
      complex cleared of proteins in transit.
AB  - The discovery of additional endogenous Golgi proteins will lead to significant
      new insights into Golgi function. To this end, stacked Golgi fractions (SGFs)
      were isolated from rat liver before (CTL SGF) and after molecules in transit
      through the Golgi were cleared by pre-treatment with cycloheximide (CHX SGF).
      Electron microscopic (EM) morphometric and biochemical analyses showed that the
      in vivo stacked morphology is retained, that > 90% of the elements can be
      positively identified as Golgi stacks and cisternae, and that transmembrane
      protein markers of the Golgi complex are enriched 300- to 800-fold over starting
      postnuclear supernatant (PNS). High-resolution two-dimensional (2-D) gel mapping
      has been carried out on the CTL PNS, CTL SII (an intermediate fraction), CTL SGF,
      CHX SGF, CHX SGF - high pH supernatant, and CHX SGF - high pH pellet. This
      analysis, coupled with immunoblotting and alignment of the 2-D gels with master
      gels, has allowed the identification of a number of known proteins and the
      preliminary characterization of the most abundant 173 Golgi-specific proteins.
      These 173 proteins have been placed into three categories: cargo, cytosolic Golgi
      associated, and resident Golgi proteins. These categories are tentative and will
      be modified as more data are acquired from immunoblotting and protein sequencing.

PMID- 9527492
TI  - Generation of proteoliposomes from subcellular fractions.
AB  - Intracellular membranes are highly dynamic, yet they retain their identity and
      functional characteristics. Integral membrane proteins, which must confer this
      specific membrane identity, remain poorly characterized at the biochemical level,
      largely because detergent-mediated solubilization is required for purification
      and analysis, and several properties of integral membrane proteins can only be
      investigated when the molecule is properly embedded in a lipid bilayer. We
      present a method for the efficient reconstitution into proteoliposomes of
      integral membrane proteins from subcellular fractions. Integral membrane proteins
      were identified on high-resolution two-dimensional gels after selective
      extraction of soluble and peripheral membrane proteins; they accounted for 8% of
      the number of resolved polypeptides. A reconstitution procedure based on membrane
      solubilization with dodecyl-octaoxyethylene (C12E8) and subsequent detergent
      removal with BioBeads SM-2 resulted in the efficient reconstitution of several
      membrane proteins into proteoliposomes of uniform density. The generated
      proteoliposomes strongly resemble the starting membrane fraction in protein
      composition. This reconstitution allows the functional characterization of
      integral membrane proteins after enrichment and/or specific (immuno)depletion.

PMID- 9527494
TI  - Acidic cytosolic proteins are preferentially imported into rat liver lysosomes.
AB  - Previous studies have reported that lysosomes isolated from human diploid
      fibroblasts and from rat liver can selectively import and degrade specific
      proteins. We have now reinvestigated this selectivity using an in vitro assay
      with rat liver lysosomes and an extract of cytosolic proteins prepared from
      cultured cells labeled to equilibriums with [35S-]methionine. Analysis by two
      dimensional gel electrophoresis and autoradiography of the cytosolic proteins
      bound to the lysosomal membrane and imported into the lysosomes shows that when
      all cytosolic proteins are simultaneously present in the in vitro assay the
      lysosomal uptake also occurs in a specific manner. These findings suggest that
      isolated lysosomes are able to discriminate among different proteins, selecting
      those with certain features for lysosomal degradation. Additional
      characterization of the cytosolic proteins which are selectively imported by
      lysosomes shows that a common structural feature of most, but not all, of these
      proteins is an acidic isoelectric point (pI <6.0) and a small or intermediate
      size. This observation is in agreement with earlier studies which established a
      relationship between the in vivo half-lives of cytosolic proteins in rat liver
      and their net charge, with acidic proteins, in general, being degraded more
      rapidly than neutral or basic proteins. The reasons for this preference are still
      uncertain, although a possible explanation is presented.

PMID- 9527493
TI  - Insulin-regulatable phosphoproteins in 3T3-L1 adipocytes form detergent-insoluble
      complexes not associated with caveolin.
AB  - Whole body glucose homeostasis is dependent on the action of insulin. In muscle
      and adipose tissues, insulin stimulates glucose uptake by inducing the
      translocation of vesicles containing the glucose transporter GLUT4 to the cell
      surface. While the mechanisms of insulin-regulated GLUT4 translocation are not
      fully understood, some signaling intermediates have been implicated in this
      process. Interestingly, some of these intermediates, including IRS-1 and PI3K,
      have been localised to the same intracellular membrane fraction as the GLUT4
      storage pool, designated here as the high-speed pellet (HSP) fraction. This
      raises the possibility that many of the downstream insulin signaling
      intermediates may be located within close proximity to intracellular GLUT4. The
      goal of this study was to test this hypothesis in 3T3-L1 adipocytes. A large
      proportion of adipocyte phosphoproteins co-fractionated in the HSP fraction. In
      an attempt to resolve insulin-regulatable phosphoproteins, we subjected 32P
      labeled subcellular fractions to two-dimensional gel electrophoresis (2-DE).
      Insulin reproducibly stimulated the phosphorylation of 12 spots in the HSP
      fraction. Most of the HSP phosphoproteins were insoluble in the nonionic
      detergent Triton X-100, whereas integral membrane proteins such as GLUT4 and
      intracellular caveolin were soluble under the same conditions. These results
      suggest that insulin-regulatable phosphoproteins in adipocytes may be organized
      in microdomains within the cell and that this assembly may act as an efficient
      conductor of the signaling proteins to rapidly facilitate downstream biological
      responses. Further study is required to establish the molecular basis for these
      detergent-insoluble signaling complexes.

PMID- 9527495
TI  - Two-dimensional electrophoresis reveals a nuclear matrix-associated nucleolin
      complex of basic isoelectric point.
AB  - A monoclonal antibody was raised against a salt-extractable fraction of nuclear
      matrix / intermediate filament scaffolds of polarized MDCK cells. The antibody
      recognized an approximately 100 kDa protein in total cell lysates and nuclear
      matrices of various human cells and tissues and stained nucleolar structures in
      immunofluorescence microscopy. By partial sequencing of five peptides derived
      from immunoprecipitated protein, the targeted antigen was found to be homologous
      to human nucleolin. After two-dimensional electrophoresis of total HeLa cell
      lysates, immunoreactive bands were detected at isoelectric point (pI) 5.5--6.1,
      characteristic for nucleolin, and at pI 8.5--9. Whereas the protein focusing at
      acidic pI was found in Triton X-100-soluble cellular fractions, the antigen
      focusing at basic pI was exclusively contained in the residual nuclear fraction
      and was solubilized upon treatment of nuclear matrices with RNAse. The component
      solubilized by RNAse treatment was still detected at basic pI in two-dimensional
      electrophoresis. However, upon immunoprecipitation of the antigen from the RNAse
      released fraction in the presence of sodium dodecyl sulfate (SDS), the nuclear
      matrix-derived antigen was positioned at pI 5--6. The present data indicate that
      the nuclear matrix-bound nucleolin is associated with ribonucleoproteins and a
      basic component resisting dissociation under conditions of isoelectric focusing.

PMID- 9527496
TI  - Natural resistance to infection with intracellular pathogens: cross-talk between
      Nramp1 and Lps genes.
AB  - This study was designed to analyze the association of Nramp1 and/or Lps genes
      with differential protein expression in macrophages in order to select candidate
      proteins that might be related to resistance/susceptibility to various microbial
      infections under the control of the Nramp1 and/or Lps genes. The macrophage cell
      lines derived from bone marrow of Nramp1 or Lps congenic mice were utilized and
      high-resolution two-dimensional electrophoreis (2-DE), separating proteins
      according to their charge and size, was used as a window into alterations in gene
      expression and a means to compare the macrophages carrying a resistant allele of
      Nramp1 gene and/or normal allele of Lps gene, with their counterparts carrying
      either a susceptible allele of Nramp1 or defective allele of the Lps gene. We
      demonstrate that the changes of constitutive levels of two proteins named
      according to their isoelectric point/molecular weight (pI/Mr), p6.6/25 and
      p7.0/22, discriminate satisfactorily not only the macrophages congenic at the
      Nramp1 gene but also the macrophages congenic at the Lps gene, thus reflecting
      their common genotype (Nramp1r, Lps[n]). Furthermore, the decreased constitutive
      levels of these proteins in macrophages carrying a defective allele of Lps but
      preserving a resistant allele of Nramp1 can be, at least in part, restored by
      stimulation with interferon gamma or lipopolysaccharide. 2-DE immunoblot analysis
      identified the p7.0/22 protein as manganese superoxide dismutase. Bcl-2 appears
      to be the best candidate for p6.6/25 as suggested by 2-DE quantitative
      alterations and Western blot analysis. These proteins are important in the
      regulation of intracellular redox balance and the regulation of apoptosis in
      macrophages and their alterations might reflect closely the transport functions
      of ions or other charged substrates suggested for Nramp1 protein.

PMID- 9527497
TI  - Biogenesis of lipoprotein(a) in human and animal hepatocytes.
AB  - The atherogenic plasma lipoprotein complex Lp(a) consists of low density
      lipoprotein (LDL) and the highly polymorphic glycoprotein apolipoprotein(a)
      covalently linked by a disulfide bridge. A size polymorphism of apolipoprotein(a)
      results from a variable number of tandemly arranged kringle IV repeats. The
      largely varying plasma concentration of Lp(a) is nonnormally distributed in the
      population and correlates inversely with the molecular mass of apolipoprotein(a).
      In vivo turnover studies have revealed that differences in Lp(a) plasma
      concentrations reflect different synthesis rather than degradation. Plasma Lp(a)
      originates exclusively in the liver. Detailed studies of the intracellular
      metabolism of apolipoprotein(a) in transfected human hepatoma cells as well as in
      primary baboon hepatocytes have revealed an unusual secretory pathway of this
      protein. Due to complex folding and processing, an immature precursor form of
      apolipoprotein(a) is retained in the endoplasmic reticulum for a prolonged time.
      This retention leads to a massive accumulation in the endoplasmic reticulum which
      stands in contrast to most secretory proteins. Since the retention time
      correlates positively with the apolipoprotein(a) isoform size, this intracellular
      mechanism could explain the inverse correlation between the isoform size and
      plasma concentrations observed in the general population. These findings
      therefore demonstrate a novel cellular regulatory mechanism lor a secretory human
      plasma protein with genetically controlled concentrations. The majority of the
      above-mentioned studies revealed another unusual feature of the biogenesis of
      Lp(a). The mature Lp(a) complex is formed, at least in the investigated cell
      models, only following separate secretion of apolipoprotein(a) and LDL-like
      particles. Work that is related to both aspects of Lp(a) formation, both from our
      laboratory and from other authors, is reviewed.

PMID- 9527499
TI  - Separation of early steps in endocytic membrane transport.
AB  - We describe a simple subcellular fractionation scheme aimed at separating early
      endosomes from the plasma membrane in view of studying the possible arrival of
      plasma membrane-bound toxins, proteins or other extracellular ligands in
      endosomes. Plasma membrane proteins were labeled with the impermeable reagent
      sulfosuccinimidyl-6-(biotinamido)hexanoate (NHS-LC) biotin at 4 degrees C. In a
      separate set of cells, early endosomes were labeled by internalization of
      horseradish peroxidase from the medium for 5 min. The first step of the
      purification, which consists of a step sucrose gradient, led to three fractions,
      respectively: enriched in biosynthetic membranes (interface 3), in plasma
      membrane and early endosomes (interface 2), and in late endosomes (interface 1).
      The second step, in which interface 2 was loaded at the bottom of a 17% Percoll
      gradient, led to the separation of the plasma membrane, including caveolae and
      cholesterol-glycolipid rafts, from early endosomes. Western blot analysis of the
      fractions from the Percoll gradient showed that the transferrin receptor, the
      small GTPases rab5 and Arf6, as well as annexin II were present both at the
      plasma membrane and in early endosomes, whereas the caveolar marker caveolin,
      1co, migrated only with the biotinylated plasma membrane proteins. We used this
      fractionation procedure to show that the pore-forming toxin aerolysin does not
      reach the endocytic compartments of baby hamster kidney (BHK) cells. The
      procedure should be generally useful in rapidly determining whether extracellular
      proteins or ligands reach endosomes.

PMID- 9527498
TI  - Flow cytometric sorting and biochemical characterization of the late endosomal
      rab7-containing compartment.
AB  - Rab7 is a small molecular weight GTPase that is known to be associated with late
      endocytic compartments. Studies in which wild-type or mutant forms of this
      protein have been overexpressed in mammalian cells have indicated that rab7 plays
      a role in controlling membrane transport between late endocytic compartments.
      However, both the precise site(s) of action and localization of rab7 remain
      unclear. In the present study, we have used density-gradient centrifugation in
      combination with a new epitope-specific flow cytometric sorting method to isolate
      rab7-containing vesicles from baby hamster kidney (BHK) cells. Electron
      micrographs of sorted elements showed a homogeneous population of vesicles that
      resembles late endosomes. The polypeptide composition of rab7-containing vesicles
      was then analyzed by two-dimensional (2-D) gel electrophoresis. Rab7-containing
      vesicles were enriched in the cation-independent mannose 6-phosphate receptor and
      especially in the precursor forms of cathepsin D. Taken together, these results
      show that the rab7-containing vesicles are a component of the endocytic pathway
      that connects late endosomes and lysosomes and in which precursor forms of
      lysosomal hydrolases, segregated from their receptor, might be included.

PMID- 9527500
TI  - A novel epitope tag for the detection of rabGTPases.
AB  - Rab GTPases are localized on the cytoplasmic surface of most intracellular
      organelles where they play a role in the regulation of vesicular transport. As it
      has been difficult to detect endogenous rab proteins by morphological methods,
      their localizations were often inferred from transfection experiments using
      epitope-tagged constructs. Because most of the available epitope tags are only
      recognitzed by mouse monoclonal antibodies they are often not suitable for double
      or triple label immunocytochemistry. To overcome this problem, we generated
      antibodies against a novel 10 amino acid X31 influenza hemagglutin epitope (NH).
      We here characterized these antibodies and document their utility for detecting
      early endosomal rab proteins N-terminally tagged with the NH decapeptide in
      morphological and biochemical assays.

PMID- 9527501
TI  - Nociceptin/orphanin FQ and the opioid receptor-like ORL1 receptor.
AB  - Homology cloning and, more recently, the sequencing of whole genomes, have
      identified many open reading frames encoding proteins of unknown function, in
      particular putative G protein-coupled membrane receptors. Identification of
      orphan receptors in this way has marked the advent of 'reverse pharmacology' to
      identify the corresponding physiological ligands. This approach has led to the
      discovery of the ORL1 (Opioid Receptor-Like 1) receptor, and of its natural
      ligand, nociceptin/orphanin FQ (noc/oFQ), the basic components of a new peptide
      based signalling pathway in the nervous system. Based on genetic criteria, the
      ORL1 and opioid receptors belong to the same family, as do noc/oFQ and opioid
      peptides. The marked structural analogy between the ORLI and opioid receptors,
      especially the kappa-opioid receptor, and the noc/oFQ and opioid peptides,
      particularly dynorphin A, is not reflected anatomically since noc/oFQ and opioid
      peptides appear to be located in separate neuronal circuits. Noc/oFQ triggers the
      same G protein-mediated signalling pathways as do opioids, however, to produce
      pharmacological effects that sometimes differ from, and even oppose, those of
      opioids. Noc/oFQ stimulates an outward K+ current and/or inhibits voltage-gated
      Ca2+ channels, thereby reducing synaptic efficacy, i.e. neuronal activity. In the
      rat, noc/oFQ is endowed with supraspinal pronociceptive/anti-opioid properties
      (it suppresses opioid-mediated analgesia), while convergent electrophysiological
      and behavioural data indicate that the peptide is a spinal analgesic. Noc/oFQ has
      not yet been found to precipitate withdrawal in morphine-tolerant rats. Nor does
      it elicit motivational effects, suggesting it lacks abuse liability. Also, by
      acting supraspinally, noc/oFQ impairs motor performance, suppresses spatial
      learning, induces feeding, and regulates basal and stress-induced release of
      pituitary hormones. Noc/oFQ is also active when administered intravenously,
      exhibiting potent smooth muscle relaxant, diuretic, and antinatriuretic
      properties. Last but not least, noc/oFQ appears to regulate stimulated immune
      function, and to be involved in neuronal differentiation. The discovery of
      noc/oFQ, a neuropeptide with multiple functions, will certainly improve our
      knowledge of brain physiology, and may find therapeutic applications, for example
      in the management of pain or hyponatremic and water-retaining diseases. However,
      given the wide distribution of noc/oFQ and its receptor, the pharmacological
      profile of noc/oFQ is likely to be incomplete, and other as yet unknown functions
      of the peptide remain to be discovered. Most helpful in this respect will be the
      identification of new ligands of the ORL1 receptor, particularly antagonists. If
      research on noc/oFQ carries on unabated at the present pace, potentially
      clinically interesting new compounds could become available in the not too
      distant future.

PMID- 9527502
TI  - Olanzapine attenuates the reinforcing effects of cocaine.
AB  - The possibility that the atypical neuroleptic olanzapine can antagonize the
      ability of cocaine to produce both conditioned place preference and self
      administration in rats was investigated. Pre-treatment with olanzapine (3.0, 4.5
      mg/kg, but not 1.5 mg/kg) significantly attenuated conditioned place preference
      produced by cocaine (10 mg/kg). However, the higher dose of olanzapine
      administered alone resulted in conditioned place aversion. Pre-treatment with
      olanzapine also produced a dose-dependent decrease in cocaine self-administration
      (0.33 mg/infusion) under a fixed-ratio 2 schedule of reinforcement. Olanzapine
      produced a similar dose-responsive attenuation in operant responding for food
      (fixed-ratio 10) suggesting that olanzapine produces a nonspecific decrease in
      operant behavior. Pre-treatment with 4.5 mg/kg olanzapine significantly
      attenuated cocaine-induced hyperactivity, whereas lower olanzapine doses had
      little effect upon cocaine-induced hyperactivity. These results suggest that pre
      treatment with olanzapine is capable of blocking the reinforcing effects of
      cocaine and illustrates the value of using multiple tests of reinforcement when
      evaluating the pharmacological effects of newer psychotherapeutic agents.

PMID- 9527503
TI  - Ethanol modulates N-methyl-D-aspartate-evoked arachidonic acid release from
      neurones.
AB  - Glutamate-evokes a Ca2+-dependent release of arachidonic acid from cultured
      neurones via the activation of NMDA and AMPA receptors. In this study we
      investigated whether exposing cultured striatal neurones either acutely or
      chronically to ethanol would modify these responses. Acute ethanol (100 mM, 15
      min) inhibited the liberation of arachidonic acid evoked by a maximally effective
      concentration of glutamate, an affect which appeared to be mediated primarily by
      a reduction in NMDA receptor responsiveness. In contrast, chronic ethanol
      exposure caused a dose-dependent increase in the glutamate, N-methyl-D-aspartate
      (NMDA) and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) evoked
      release of arachidonic acid, although ethanol was less potent at the AMPA
      response. Basal responses were not altered by acute or chronic ethanol and the
      concentrations of ethanol employed were not toxic. Chronic ethanol (100 mM, 48 h)
      increased NMDA-mediated neuronal damage at sub-maximal concentrations of the
      agonist, suggesting that an enhanced mobilisation of arachidonic acid may underly
      the potentiated excitotoxic neuronal loss observed following exposure to ethanol.

PMID- 9527504
TI  - Group II and III metabotropic glutamate receptors modulate paired pulse
      depression in the rat dentate gyrus in vitro.
AB  - We have investigated the effect of a number of group I, II and III metabotropic
      glutamate (mGlu) receptor agonists and antagonists on paired pulse depression in
      the medial perforant path of the rat dentate gyrus in vitro. A triphasic pattern
      of a large depression at short intervals (10-50 ms), a reduction of this
      depression at intermediate intervals (50-200 ms) and again a large depression at
      late intervals (> 200 ms) was observed. The group I mGlu receptor agonist, (S)
      3,5-dihydroxy phenylglycine ((S)-DHPG; 20 microM) had no significant effect on
      paired pulse depression at any interstimulus intervals. The mGlu receptor group
      II and III agonists, L-CCG-1 ((2S,3S,4S)-alpha-(carboxy-cyclopropyl)-glycine),
      DCG-IV ((2S,1'R,2'R,3'R)-2-2',3'-dicarboxy cyclopropylglycine), 1S,3R-ACPD (1S,3R
      1-aminocyclopentate-1,3-dicarboxylic acid) and L-AP4 (L-2-amino-4-phosphono
      butyric acid) reduced paired pulse depression at interstimulus intervals of 200
      ms or less. Application of the non specific mGlu receptor antagonist, MCPG (alpha
      methyl carboxy-phenylglycine; 200 microM) completely inhibited the 1S,3R ACPD
      induced reduction in paired pulse depression but was without effect on the L-AP4
      response. The relatively specific group II antagonist MCCG ((2S,3S,4S)-2-methyl-2
      carboxy cycloproprylglycine) at 200 microM and 500 microM, attenuated but did not
      completely inhibit the DCG-IV induced reduction of paired pulse depression. The
      putative group III pre-synaptic mGlu receptor antagonist alpha-methyl-L-AP4 and
      MSOP ((RS)-alpha-methylserine-O-phosphate) both at 200 microM inhibited the L-AP4
      induced reduction in paired pulse depression at intermediate phase interstimulus
      intervals but not at early interstimulus intervals. These results specifically
      demonstrate the involvement of group III and III mGlu receptor ligands in the
      modulation of paired pulse depression in the medial perforant pathway.

PMID- 9527505
TI  - Characterization of alpha1-adrenoceptor subtypes in facilitation of rat spinal
      motoneuron activity.
AB  - The subtypes of alpha1-adrenoceptor mediating facilitation of alpha-motoneuron
      activity in adult rat spinal cord were examined. The potencies of agonists and
      antagonists were compared, using extracellular single unit recordings made in
      spinal cord slices isolated from adult rats. Catecholamines (epinephrine,
      norepinephrine), phenylethylamines (phenylephrine, methoxamine) and imidazolines
      (clonidine, oxymetazoline, St587 (2-(2-chloro-5-trifluoromethyl-phenylimino)
      imidazoline)) enhanced motoneuron activity. Catecholamines and phenylethylamines
      elicited maximal responses but imidazolines elicited submaximal responses. The
      potencies of the agonists were similar to their affinities for alpha1A
      adrenoceptors. The alpha1A-adrenoceptor agonist SDZ NVI 085 ((-)-(4aR,10aR)
      3,4,4a,5,10,10a-hexahydro-6-methoxy-4-methyl-9-methylthio-2H-naphth[2,3b]-1,4
      oxazine) behaved as a partial agonist with a maximal response of about 75% and
      this response was not inhibited by chloroethylclonidine. Pretreatment with
      chloroethylclonidine produced a rightward shift of the phenylephrine response
      curve but caused little reduction in the maximal response. Prazosin, 5-methyl
      urapidil, WB4101 (2-([2,6-dimethoxyphenoxyethyl] aminomethyl)-1,4-benzodioxane)
      and BMY7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8azaspiro[4.5]decane
      7,9-dione dihydrochloride) concentration dependently inhibited the facilitation
      of alpha-motoneuron activity produced by phenylephrine. The order of inhibitory
      potency was similar to that for their alpha1A-adrenoceptor binding site affinity.
      Therefore, it seems that alpha1A-adrenoceptors may be functionally predominant in
      the facilitation of rat spinal motoneuron activity.

PMID- 9527506
TI  - Effects of a psychostimulant drug sydnocarb on rat brain dopaminergic
      transmission in vivo.
AB  - Transcerebral microdialysis was used to evaluate the effect of a psychostimulant
      drug, sydnocarb (3-(beta-phenylisopropyl)-N-phenylcarbamoylsydnonimine), on the
      extracellular levels of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and
      homovanillic acid (HVA) in the dorsal striatum and nucleus accumbens of freely
      moving rats. Sydnocarb dose dependently (4.4, 8.75 and 17.5 mg/kg, i.p.) induced
      a relatively modest (up to 350% of control) and long-lasting (up to 6 h) increase
      in dopamine extracellular level in the rat dorsal striatum. The drug at 8.75
      mg/kg, i.p., produced an approximately similar increase in dopamine efflux in the
      dorsal striatum and in the nucleus accumbens of freely moving rats. Sydnocarb had
      no effect on DOPAC or HVA extracellular levels in the rat basal ganglia in vivo
      at any dose studied. It is important that the drug increased the efflux of
      dopamine in a tetrodotoxin-sensitive and Ca2+-dependent manner. Measurements of
      behavioral parameters in non-operated rats revealed that sydnocarb markedly
      increased locomotor activity and induced stereotyped behavior. These data suggest
      that the stimulant action of sydnocarb is accompanied by a facilitation of
      central dopaminergic transmission involving an increase in Ca2+-dependent
      vesicular dopamine efflux.

PMID- 9527507
TI  - Effect of Ca2+/calmodulin-dependent protein kinase II inhibitors on the
      neurogenic cerebroarterial relaxation.
AB  - In canine cerebral artery strips contracted with prostaglandin F2alpha,
      transmural electrical stimulation (5 Hz for 40 s) produced a relaxation which was
      abolished by tetrodotoxin. The neurogenic response was inhibited moderately by
      [S]-5-isoquinolinesulfonic acid,4-[2-[(5-isoquinolinyl-sulfonyl)methylamino]-3
      oxo-(4-phenyl-1-piperazinyl)-propyl] phenyl ester (KN62), an inhibitor of Ca2+
      /calmodulin-dependent protein kinase II, which however did not alter or only
      slightly reduced the relaxant response to electrical nerve stimulation in canine
      coronary arterial strips that is mediated via beta-adrenoceptors stimulated by
      norepinephrine. Nicotine-induced relaxation, mediated by nitric oxide (NO)
      derived from perivascular nerves, was also attenuated by KN62, whereas the
      response to exogenous NO was unaffected. The nicotine-induced increase in the
      cyclic GMP content in cerebral arteries was depressed by KN62. The neurogenic
      relaxation was not influenced by phorbol 12-myristate 13-acetate, an activator of
      protein kinase C. 8-Bromo-cyclic GMP and 8-bromo-cyclic AMP did not significantly
      alter the response to nerve stimulation. It is concluded that the phosphorylation
      pathway involving Ca2+/calmodulin-dependent protein kinase II, but not other
      protein kinases so far tested, appears to be involved in the function of
      vasodilator nerves innervating the cerebral artery.

PMID- 9527508
TI  - Platelet eicosanoids and the effect of captopril in blood pressure regulation.
AB  - We investigated the eicosanoid synthesis of platelets of Wistar and of Okamoto
      spontaneously hypertensive rats (SHR), and the effect of captopril in vitro,
      using [14C]arachidonic acid as a tracer substrate and chromatographic
      determination. Lipoxygenase activity was elevated, while the formation of
      cyclooxygenase products was reduced in SHR platelets, compared to those of Wistar
      rats. This difference might play a role in the pathomechanism of hypertension in
      SHR. In SHR with lower blood pressure, captopril reduced thromboxane synthesis,
      while in SHR with higher blood pressure thromboxane synthesis was unchanged, but
      the synthesis of prostaglandin D2, a potent vasodilator, and of 12-L-hydroxy
      5,8,10-heptadecatrienoic acid, a stimulator of endothelial prostacyclin
      formation, was increased. We may conclude that, in spite of the missing
      angiotensin converting enzyme in platelets, a direct effect on platelet
      eicosanoid synthesis could contribute to the blood pressure decreasing effect of
      captopril.

PMID- 9527509
TI  - Neuropeptide Y Y1 receptor blockade does not alter adrenergic nerve responses of
      the rat tail artery.
AB  - Using the selective neuropeptide Y Y1 receptor antagonist, BIBP3226 [(N2
      (diphenylacetyl)-N-[(4-hydroxyphenyl)methyl]-D-argininamide], the role of
      endogenous neuropeptide Y in mediating vasoconstrictor responses to adrenergic
      nerve stimulation was investigated by recording isometric force from isolated rat
      tail artery segments. BIBP3226 had no effect on contractile responses to
      adrenergic nerve stimulation (10 pulses; 0.5-2 Hz), but it completely blocked the
      enhancement of contraction produced by exogenous neuropeptide Y. When frequency
      and train length of the transmural nerve stimulation were increased (100 pulses;
      1-16 Hz), contractile responses were still unaffected by BIBP3226. A peptidase
      inhibitor mixture known to increase responses to exogenous neuropeptide Y was
      added; however, BIBP3226 still did not influence contractile responses to
      adrenergic nerve stimulation. Thus, contractile responses to adrenergic nerve
      stimulation in the rat tail artery do not appear to involve the release and
      postjunctional action of endogenous neuropeptide Y; however, exogenous
      neuropeptide Y does potentiate these responses by acting on Y1 receptors.

PMID- 9527510
TI  - Serotonergic mechanisms involved in calcitonin potentiation of kappa-opioid
      receptor-mediated effects on adrenal secretion.
AB  - Calcitonin can selectively modulate the effects of opioids on the rat
      hypothalamic-pituitary-adrenal axis and increase the release of corticosterone
      induced by a kappa-opioid receptor agonist. Considerable evidence supports the
      involvement of opioid and serotonergic systems in the analgesic effect of
      calcitonin. In this study, the involvement of hypothalamic serotonergic pathways
      in the calcitonin potentiation of the effect of (trans-(+/-)-3,4-dichloro-N
      methyl-N-[2-(1-pyrrolidinyl) cyclohexyl]-benzeneacetamide methane sulphonate (U
      50,488H) on the secretion of corticosterone was examined. The correlation between
      the calcitonin-induced potentiation of the pituitary adrenal response to U
      50,488H and changes in serotonin turnover was evaluated. Our results show that
      the increase in the release of corticosterone induced by treatment with
      calcitonin + U-50,488H was not evident when the turnover of serotonin was
      decreased by inhibition of its synthesis with m-hydroxybenzylhydrazine (NSD 1015)
      or by blockade of its metabolism with trans-2-phenylcyclopropylamine
      (tranylcypromine). Although other factors can not be discarded, from the present
      data it can be suggested that the serotonergic system plays an important role in
      the interaction calcitonin-kappa-opioid receptor agonist in the hypothalamic
      pituitary-adrenal axis.

PMID- 9527512
TI  - Digital Radiology: deficiencies, failures and other adventures.

PMID- 9527511
TI  - Characterization of binding sites for the omega3 receptor ligands [3H]PK11195 and
      [3H]RO5-4864 in human brain.
AB  - The kinetics and pharmacology of the isoquinoline and benzodiazepine binding
      sites of the omega3 or peripheral-type benzodiazepine receptors were studied
      using the specific ligands [3H] 7-chloro-5-(4-chlorophenyl)-1,3-dihydro-1-methyl
      2H-1,4-benzodiazepin  -2-one ([3H]PK11195) and [3H]1-(2-Chlorophenyl)-N-methyl-N
      (1-methylpropyl)-3-isoquinolinecarb  oxamide ([3H]RO5-4864), respectively.
      Binding of both ligands was saturable, reversible, displayed nanomolar affinity,
      and best fit to a single site model. Occipital cortex and cerebellum displayed
      highest and lowest densities of binding sites respectively; for both ligands.
      Bmax values of [3H]PK11195 were several-fold higher than that of [3H]RO5-4864 in
      all regions studied consistent with their binding to distinct subunits of the
      human peripheral-type benzodiazepine receptor heteromeric complex. However, the
      isoquinoline and benzodiazepine ligands were found to be mutually competitive at
      nanomolar concentrations suggesting allosteric interactions between these two
      sites. Competition binding experiments showed that the binding of both ligands
      was displaced by diazepam with Ki values in the nM range, and by clonazepam in
      the microM range. The novel peripheral-type benzodiazepine receptor ligand 2-(4
      fluorophenyl)-N,N-di-n-hexyl-1H-indole-3-acetamide (FGIN1-27) displaced only
      [3H]PK11195 binding with high potency. Heterogeneity of the two sites is
      observed, manifested by their differential susceptibility towards detergents and
      alcohols. Histidine residue modification by diethylpyrocarbonate treatment
      abolished only [3H]PK11195 binding but had no effect on [3H]RO5-4864 binding.
      These studies demonstrate that the isoquinoline and benzodiazepine sites on the
      peripheral-type benzodiazepine receptor in human brain manifest many
      pharmacological characteristics that are distinct from each other and from rodent
      brain peripheral-type benzodiazepine receptors.

PMID- 9527513
TI  - Digital imaging in rotational panoramic radiography.

PMID- 9527514
TI  - Computerized medical image interpretation.

PMID- 9527515
TI  - Impact of information technology on image-based data processing.

PMID- 9527516
TI  - Characterization of Streptomyces sp. strain DRS-1 and its ampicillin
      transformation product.
AB  - Incubation of ampicillin with whole cells of Streptomyces sp. DRS-1 resulted in
      accumulation of four compounds different from ampicillin. One of them was
      isolated, purified and partially characterized. On the basis of spectroscopic
      characteristics, RF value and antibacterial activity the compound was identified
      as cephalexin. It could also be obtained from ampicillin by using crude protein
      extract of the strain.

PMID- 9527517
TI  - Studies on mercury-detoxicating enzymes from a broad-spectrum mercury-resistant
      strain of Flavobacterium rigense.
AB  - Flavobacterium rigense strain PR2, a broad-spectrum mercury-resistant bacterium
      abundantly present in soil exhibited multiple metal resistance properties.
      Mercury resistance was due to the sequential action of two mercury-detoxicating
      enzymes, organomercurial lyase and mercuric reductase. The levels of these enzyme
      activities were determined using different mercury compounds as inducers and
      substrates. Mercuric reductase was partially purified from the bacterium and the
      physicochemical properties of the enzyme were studied. The effect of several
      enzyme inhibitors and heavy metal ions on the enzyme activity was also studied.

PMID- 9527518
TI  - [Progress in surgery of esophageal cancer and the prospect for future
      development].

PMID- 9527519
TI  - Changes in sequestered leukocytes and platelets in the pulmonary microvasculature
      of rats with monocrotaline-induced pulmonary hypertension.
AB  - The role of leukocytes (WBCs) and platelets (PLTs) in the pulmonary circulation
      may be important in the development of monocrotaline (MCT)-induced pulmonary
      hypertension in rats. We investigated the changes in WBCs and PLTs in the
      pulmonary microvasculature during the development of chronic pulmonary
      hypertension in MCT rats by real-time confocal scanning laser microscopy. The
      number of WBCs sequestered in the pulmonary microvasculature increased
      significantly from day 7 after MCT injection, but no further increase occurred
      from days 14-28. The number of PLTs sequestered in the pulmonary microvasculature
      increased significantly from day 7 after MCT injection, and reached a peak on day
      14. However, the number of PLTs sequestered on days 21 and 28 after MCT injection
      was significantly lower than on day 14. These findings suggest that PLTs mainly
      contribute to the initial and middle stages of the development of MCT-induced
      pulmonary hypertension in rats, while WBCs mainly contribute to the middle and
      late stages.

PMID- 9527520
TI  - Measurement of blood perfusion in the dental pulp with laser Doppler flowmetry.
AB  - The reproducibility of laser Doppler flowmetry (LDF) in measuring the perfusion
      of the dental pulp was investigated. A second aim was to establish if the LDF
      signal from the dental pulp can be influenced by physiological stimuli, e.g.
      postural changes. A third aim was to apply the technique to clinical measurements
      of pulp perfusion in patients undergoing orthodontic therapy. A custom splint to
      position the probe was fabricated for 10 subjects, and measurements of pulpal
      perfusion in the maxillary six anterior teeth were repeated on eight occasions
      with the subject seated. Further, measurements of the dental pulp perfusion in
      one tooth were repeated with the subject in a standing and supine position. Mean
      perfusion (arbitrary perfusion units) for individual teeth varied from 2.7 for a
      central incisor to 15.5 for a lateral incisor. Perfusion was greatest for lateral
      incisors and least for central incisors. Pulpal perfusion was significantly
      higher in a supine than in a standing or sitting position. Initial clinical
      experience with LDF encourages further investigation of its potential as a
      diagnostic tool for determining pulp vitality. Preliminary experimental results
      suggest that LDF will be a valuable source indicating pulpal response to
      orthodontic therapy with fixed appliances.

PMID- 9527521
TI  - Different effects of anesthetics on spontaneous leukocyte rolling in rat skin.
AB  - In immunological reactions, leukocytes need to travel from the intravascular
      space through the vessel wall into the surrounding tissue. The first step in this
      process is leukocyte rolling, which has often been studied in anesthetized
      animals. In this study, we investigated the effect of pentobarbital, Hypnorm and
      both components of the latter, fentanyl and fluanisone, on this primary leukocyte
      endothelial cell interaction. Using intravital brightfield video microscopy,
      observations were made in postcapillary venules in the intact skin of the
      nailfold of trained conscious Lewis rats. Subsequently, the animals were
      anesthetized and observations were made in vivo. Leukocyte rolling was
      significantly elevated after injection of Hypnorm or fentanyl, while
      pentobarbital and fluanisone had no effect. None of the anesthetics affected
      leukocyte rolling velocity. Blood flow was significantly increased only after
      injection of Hypnorm and fluanisone. No correlation existed between the relative
      changes in leukocyte rolling and concomitant changes in blood flow. The results
      show that the level of leukocyte rolling can be affected by anesthetics. These
      changes are probably not mediated by changes in local hemodynamics. Pentobarbital
      anesthesia does not influence leukocyte rolling. Therefore, pentobarbital is a
      suitable anesthetic for observation of leukocyte rolling in skin. Hypnorm
      significantly increases the level of rolling in skin venules. This effect seems
      to be caused mainly by fentanyl.

PMID- 9527522
TI  - A 5.0-kD heparin fraction systemically suppresses VEGF165-mediated angiogenesis.
AB  - The systemic effect of heparin fractions with mean molecular masses of 2.5, 5.0
      and 16.4 kD on angiogenesis induced by vascular endothelial growth factor isoform
      165 was studied using the truly quantitative rat mesenteric-window angiogenesis
      assay. The angiogenic treatment with 5 ml of VEGF165 at 480 pM was given
      intraperitoneally on days 0-4 and heparin fractions were given subcutaneously on
      days 0-13; animals were sacrificed on day 14. As the overlaps between the
      molecular mass distributions of the three fractions were relatively small, they
      essentially represent three different populations of heparin molecules. The doses
      of the heparins given were equal in terms of weight, but different in terms of
      the number of molecules and biologic activity. Angiogenesis was assessed in terms
      of vascularized area (VA), a measurement of microvascular spatial extension, and
      microvascular length (MVL), a measurement of microvascular density, using
      technically independent variables and image analysis. The total microvascular
      length was computed from VA x MVL. Treatment with the 5.0-kD fraction suppressed
      angiogenesis significantly in statistical terms compared with treatment with 2.5-
      and 16.4-kD heparins and the saline in controls. Interestingly, the 2.5-kD
      heparin fraction which was used here has previously been shown statistically
      significantly to suppress angiogenesis mediated by basic fibroblast growth factor
      in the same experimental system. Our data thus suggest that the systemic
      angiosuppressive effect of heparin in different mammalian angiogenic reactions is
      distinctly related to structural features such as molecular size.

PMID- 9527523
TI  - An improved intravital microscopy system.
AB  - The use of intravital microscopy as a tool for studying the microcirculation has
      increased greatly over the last several decades. Early microscopes provided the
      first pictures of the microcirculation, but were cumbersome to use and subjected
      the tissue to a high light intensity, a problem which has recently become the
      subject of much discussion. The goal of this project was therefore to build a
      more ergodynamic microscope which minimizes the light exposure to the tissue. The
      automation of the microscope controls provides a platform on which other options
      can be built into the microscope, such as an autofocus feature. Furthermore, the
      use of the Optimas software also opens the possibility for on-line data
      processing.

PMID- 9527524
TI  - A one-piece plexiglass access chamber for subcutaneous implantation in the dorsal
      skin fold of the mouse.
AB  - This technical report describes the production and installation of a newly
      developed, one-piece, light-weight (0.6 g) access plexiglass chamber for the
      dorsal skin fold of the mouse.

PMID- 9527525
TI  - Reference sample microsphere method to measure blood flow effects on small
      intestinal perfusion in the rat.
AB  - To evaluate whether the microsphere method, including the necessary surgical
      procedures, for blood flow determination creates hemodynamic stress and a
      secondary reduction in small intestinal perfusion, we monitored the small
      intestinal perfusion with laser Doppler (LD) fluxmetry in 3 groups of Sprague
      Dawley rats. Group I was studied during two microsphere injections without
      manipulation, group II was subjected to mesenterial-root occlusion during the
      second injection, and for group III, vasodilatation with papaverine preceded the
      second injection. While cardiac output and kidney blood flow were constant at the
      two microsphere injections, mean blood pressure (p < 0.05) and hematocrit (p <
      0.01) significantly decreased in all 3 groups. Blood glucose increased
      significantly (p < 0.01). LD values also declined significantly (p < 0.05)
      between the start and end of experiments. In group I, the initial values of 9.5
      perfusion units (PU) (5-23) decreased to 6.5 PU (3-12), in group II, 10.5 PU (5
      24) decreased to 7.0 PU (4-15) and in group III, 9.0 PU (5-13) decreased to 5.5
      PU (4-12). In conclusion, these findings suggest that the microsphere technique
      with two injections of spheres and reference sample withdrawals may affect the
      perfusion of the small intestine in the Sprague-Dawley rat.

PMID- 9527526
TI  - Is local metabolism the basis of the fractal vascular structure in the heart?
AB  - The distribution of blood flow in the heart muscle is very heterogeneous and
      shows a self-similar fractal pattern, extending to small spatial scales. It is
      very likely that local oxygen consumption is more or less proportional to local
      blood flow and that local aerobic metabolism also is very heterogeneous. It is
      not yet clear whether local metabolism is heterogeneous in origin and the
      distribution of flow has secondarily adapted to metabolism, or, the other way
      around, whether flow is primarily heterogeneous because of the irregular
      structure of the coronary tree and flow has adapted to metabolism. Little is
      known yet about the developmental and adaptive mechanisms which bring about
      mutual adjustment between vascular growth and local metabolic demand, and genes
      and growth factors involved in shaping the structure of the coronary tree have
      only begun to be identified. Fractal and nonlinear dynamic mathematical models
      generate complex heterogeneous structures from simple nonlinear deterministic
      rules which are recursively applied. Such nonlinear models may thus help to
      explain the generation of large vascular trees regulated by synergy of a limited
      number of genes and signaling molecules. This may explain the relative regularity
      of space filling of the vascular tree and the asymmetry of branching and flow
      distribution in the tree.

PMID- 9527527
TI  - Synergetic interpretation of patterned vasomotor activity in microvascular
      perfusion: discrete effects of myogenic and neurogenic vasoconstriction as well
      as arterial and venous pressure fluctuations.
AB  - Synergetic concepts allow to identify emergent coordination phenomena between
      interacting physiological systems, for example between the cutaneous
      microcirculation, the sympathetic nervous system and the cardiac and pulmonary
      systems. The temporal patterns (oscillations of various frequencies) that are
      found in the data obtained with laser-Doppler anemometers (LDA; e.g. Periflux 2
      used in the study) can be investigated by simultaneous recording of
      photoplethysmographic data obtained in the identical region of interest, as well
      as in cutaneous regions treated with vasoparalytic procedures which permit to
      record the dynamics of the arterial system. These strategies were applied to
      studies in the cutaneous microcirculation (volar side of the index fingers) as
      well as to mucosal microcirculation (maxillar gingiva) in healthy subjects and in
      patients suffering from autonomic dysfunction (cutaneous microcirculation) or
      gingivitis. By this procedure, it could be corroborated that - contrary to
      popular notions - the temporal fluctuations in the LDA records do not necessarily
      reflect myogenic vasomotion, but can have multiple causes. In a confirming recent
      study [Schmid-Schonbein et al., J Auton Nerv Syst, 57, 136-140, 1996], we have
      demonstrated that the LDA fluctuations under conditions of normal ambient
      temperature and hand position most likely reflect neurogenic vasoconstriction.
      Under exceptional conditions, different patterns emerge. Prolonged exposure to
      ambient temperature (18 degrees C) leads to marked vasoconstriction, with
      occasional vasodilator escape ('miniature hunting reaction'). Normal subjects
      under gravitational load and in warm environment (28 degrees C ambient) silence
      their neurogenetic vasoconstriction reactions, which allows sinusoidal vasomotion
      to dominate. A similar phenomenon is seen in neuropathic patients at 21-24
      degrees C (presumably due to structural defects). Fluctuations in LDA signal
      taken from the healthy gingiva are entrained to arterial, those taken from
      inflamed gingiva to respiratory activity. The theory and practice of nonlinear
      analysis is discussed, and data compression procedures allowing to portray
      characteristic temporal patterns for future diagnostic procedures are presented.

PMID- 9527528
TI  - Vascular smooth muscle, a multiply feedback-coupled system of high versatility,
      modulation and cell-signaling variability.
AB  - Under normal conditions, the various vascular regulatory effector influences are
      interwoven in a dynamic, and not a static, circulatory system. The reaction of a
      smooth muscle cell is thus reflected only incompletely by the stationary
      activation curve 'developed tension versus membrane potential'. The missing time
      domain in this relationship is a reflection of our as yet limited understanding
      of the system's behavior in space and time. It should be emphasized that the
      rhythmogenic properties of vascular smooth muscle are closely coupled to a
      functioning circulation. The electrical and mechanical oscillations, which can be
      traced back to rhythmic activity of the active, electrogenic Na+/K+ pump, could
      originate in the allosteric qualities of the enzyme phosphofructokinase (PFK).
      Thus, PFK represents a rhythmogenic enzyme which may serve as an example of the
      connection between the biological properties on a molecular level and the
      spatiotemporal system's behavior. The cardiovascular system and its rhythmicity
      may be dominated by only a few control points, one of which is distinguished by
      the viscoelastic properties of a blood flow sensor macromolecule. Therefore, the
      three prominent control points - PFK, (Na+ + K+)-ATPase and flow sensor
      conformation - acting as negatively feedback-coupled, nonlinear synergetic order
      parameters, are sufficient to initiate the periodic events in the cardiovascular
      system and to provide a plausible explanation for their causal origin.

PMID- 9527529
TI  - Cardiovascular monitoring of elective aortic aneurysm repair using methods of
      chaos analysis.
AB  - INTRODUCTION: Biological signals like arterial blood pressure (ABP) and
      electrocardiograms are usually displayed in a linear fashion. The often very
      complex structure may, however, be better described by phase space plots and time
      delayed vectors, enabling an advantageous display of the dynamics contained in
      the signal. The potentials of such a display were investigated during elective
      aortic aneurysm repair, where profound haemodynamic changes frequently occur.
      METHOD: The peripheral volume pulse was recorded at a digit using noninvasive
      near infrared photoplethysmography (NIRP). All patients (n = 20, mean age 72.8
      years) were invasively monitored using arterial and Swan Ganz catheters. The ABP
      signal was continuously recorded with a computer (sample rate 128 Hz). Two
      different phase space plots, [x(t), y(t + 8/128 s) and x(t), d(x(t + 8/128 s) -
      x(t))/dt] were calculated for the NIRP and the ABP signals and continuously
      displayed. The stability was subjectively assessed and the fractal dimension
      calculated using the 'Hausdorff dimension'. The correlation between stability,
      fractal dimension and frequently used parameters of patient monitoring were
      investigated. RESULTS: All patients included in the study had an uncomplicated
      operation. Cardiac index (CI) and oxygen delivery (DO2) increased, and systemic
      vascular resistance (SVR) decreased following declamping of the aorta. The ABP
      signal was generally more stable. After declamping of the aorta, 14 of 16 NIRP
      signals became unstable, and 9 of 14 ABP signals destabilised. The time required
      for stabilisation of the signal varied between the individual patients. Thirty
      minutes after declamping, 11 of 12 ABP signals were stable, whereas 3 out of 9
      NIRP signals still revealed an unstable pattern. A fractal dimension was
      calculated by box counting, which revealed a linear regression over two orders of
      magnitude in a log-log plot (Hausdorff dimension between 1.19 and 1.71). The mean
      fractal dimension for NIRP was significantly higher than that of the ABP signal.
      On clamping and declamping of the aorta, a trend to a higher fractal dimension (p
      = 0.08) was observed for both signals analysed. No correlation was observed
      between the fractal dimension and ABP, SVR index, CI, DO2 index and oxygen
      consumption. DISCUSSION: The dynamic changes of the signals were emphasised when
      they were displayed as phase space plots calculated by time-delayed vectors. The
      time series of the signal revealed a fractal dimension, and the observed increase
      at the critical time points of the operation, where the need for cardiovascular
      regulation is most pronounced, support the contention that a physiological system
      based on non-linear behaviour may enable a rapid response to haemodynamic
      challenges. An on-line display of phase space plots calculated by time-delayed
      vectors may in future provide a valuable method of monitoring for high-risk
      patients.

PMID- 9527531
TI  - Reports from the British Columbia Office of Health Technology Assessment
      (BCOHTA). Routine ultrasound imaging in pregnancy: how evidence-based are the
      guidelines?

PMID- 9527530
TI  - Long-term registration of cutaneous microcirculation during general anesthesia.
AB  - The temporal dynamics of the systemic arterial pressure can be monitored
      noninvasively from the skin of the earlobe or forehead by photoplethysmography
      under the provision that the active control of the microcirculatory perfusion is
      eliminated. Using this approach, we have been able to detect a highly stable
      blood pressure rhythm in the range of 0.15 Hz during psychophysical relaxation or
      sleep. The aim of the present study was to investigate the occurrence and
      behavior of blood pressure rhythms below 0.2 Hz during general anesthesia. In 30
      patients (ASA groups I-II) undergoing basic surgical procedures,
      photoplethysmographic recordings from the earlobe were made during the whole time
      of anesthesia. The recorded signals were divided into segments of 200 s of
      duration, the temporal structure of which was analyzed by fast Fourier transform.
      Different characteristic patterns of rhythmical behavior were detected: (1)
      absence of activity below 0.2 Hz ('low-frequency range'); (2) slow sinusoidal
      rhythmicity below 0.05 Hz; (3) 'chaotic' behavior, i.e. multiple incoherent
      fluctuations without stationary periods or amplitudes; (4) short-term rhythmical
      activity at about 0.15 Hz, and (5) long-term rhythmical activity at about 0.15
      Hz. In patients sufficiently sedated to eliminate low-frequency activity,
      rhythmicity could sometimes be triggered by certain surgical stimuli, the
      response to which was suppressed by injection of opioids. The data presented
      strongly suggest that rhythmical perfusion patterns of the cutaneous
      microcirculation could serve as an indicator for the depth of anesthesia.

PMID- 9527532
TI  - Reports from the Conseil d'Evaluation des Technologies de la Sante du Quebec
      (CETS). The cochlear implant in adults, adolescents, and children.

PMID- 9527533
TI  - Reports from the Conseil d'Evaluation des Technologies de la Sante du Quebec
      (CETS). Percutaneous transluminal coronary angioplasty: update of application and
      standards for utilization.

PMID- 9527534
TI  - Reports from the British Columbia Office of Health Technology Assessment
      (BCOHTA). Incorporating clinical effectiveness debates into hospital technology
      assessment: the case of laser treatment of benign prostatic hyperplasia.

PMID- 9527535
TI  - Distribution of urocortin-like immunoreactivity in the central nervous system of
      the rat.
AB  - Urocortin was recently cloned from the rat midbrain. Urocortin is a member of the
      corticotropin releasing factor (CRF) peptide family and shows 45% sequence
      identity to CRF and 63% sequence identity to urotensin. It binds with a high
      affinity to CRF1 and CRF2 receptors, resulting in the stimulation of their
      adenylate cyclase activity. We used a polyclonal antibody against rat urocortin
      to define the distribution of urocortin-like immunoreactivity in the rat central
      nervous system. Several immunostained cell bodies were found in the supraoptic,
      paraventricular, and ventromedial hypothalamic nuclei. A large number of neurons
      with urocortin-like immunoreactivity were seen in the dorsolateral tegmental
      nucleus, in the linear and dorsal raphe nuclei, and in the substantia nigra. The
      most abundant immunoreactive (ir) perikarya were found in the Edinger-Westphal
      nucleus. Some neurons showed immunoreactivity in the interstitial nucleus of
      Cajal, the nucleus of Darkeschewitsch, and the periaqueductal gray. A dense
      immunoreactive fiber network was found in the lateral septal area. Some faintly
      stained axon terminals were observed among urocortin-ir perikarya in the
      supraoptic and paraventricular nuclei, in the central and periaqueductal gray,
      and in the Edinger-Westphal nucleus. No fibers with urocortin-ir were seen in the
      median eminence or the posterior pituitary. The distribution of urocortin-ir
      overlapped with the expression of the mRNA for the CRF2 receptor in several brain
      areas. These data support the hypothesis that this peptide is the endogenous
      ligand for the CRF2 receptor. Urocortin has been implicated in various endocrine
      responses, such as blood pressure regulation, as well as in higher cognitive
      functions.

PMID- 9527537
TI  - Cocaine- and amphetamine-regulated transcript peptide immunohistochemical
      localization in the rat brain.
AB  - Cocaine- and amphetamine-regulated transcript (CART) is a brain-enriched mRNA
      with a protein product(s) that is a candidate brain neurotransmitter. We have
      developed antisera to CART peptide fragment 106-129 and have demonstrated
      specific immunoreactivity (IR) at the light microscopic level throughout the
      brain, spinal cord, and retina. All brain nuclei previously shown to express CART
      mRNA are now shown to contain CART peptide IR. Although it is premature to define
      CART peptide(s) as a neurotransmitter(s), the localization found here suggests an
      involvement of CART in many processes. CART peptide staining in the nucleus
      accumbens and basolateral amygdala continue to suggest a role in drug-induced
      reward and reinforcement. Staining in the olfactory bulbs, the cortical barrels,
      the retina and its projection areas, the thalamic nuclei, the lateral and dorsal
      horns of the spinal cord, and the nuclei of the solitary tract are compatible
      with a major role for CART in sensory processing and autonomic regulation. CART
      peptides appear to colocalize with some classical neurotransmitters and appear to
      occur in peripheral neurons as well.

PMID- 9527538
TI  - Fiber outgrowth from anterior hypothalamic and cortical xenografts in the third
      ventricle.
AB  - Fetal grafts of the anterior hypothalamus (SCN/AH) containing the suprachiasmatic
      nucleus (SCN) restore circadian rhythms to SCN-lesioned host hamsters and rats
      following implantation into the third ventricle. Previous studies suggest that
      intraventricular SCN/AH grafts are variable in their attachment sites, the extent
      of their outgrowth, and the precise targets innervated in the host brain.
      However, the use of different methods to analyze graft outgrowth in this model
      has previously led to inconsistent results. We have reevaluated the outgrowth of
      fetal rat SCN/AH grafts implanted in the third ventricle of hamsters by using two
      methods: the carbocyanine dye, 1,1'dioctadecyl-3,3'-tetramethylindocarbocyanine
      percholate (DiI), was placed directly onto grafted tissue; and a donor-specific
      neurofilament marker was used in conjunction with xenografts. We examined the
      specificity of outgrowth by comparing SCN/AH xenografts with that of control
      cortical (CTX) xenografts. To evaluate whether SCN/AH graft efferents arise from
      the donor SCN, we used micropunch grafts that contained minimal extra-SCN tissue.
      The results show that the use of a donor-specific neurofilament marker reveals
      more extensive SCN/AH graft outgrowth than DiI. SCN/AH graft efferents project
      into areas normally innervated by the intact SCN. However, this outgrowth is
      variable among graft recipients, is not specific to SCN/AH tissue, and does not
      necessarily derive from the donor SCN. The precise functional role of neural
      efferents arising from SCN/AH grafts in the restoration of circadian clock
      function and the extent of SCN-derived efferents remain to be determined.

PMID- 9527536
TI  - Mechanisms of enhancement of neurite regeneration in vitro following a
      conditioning sciatic nerve lesion.
AB  - To examine the mechanisms responsible for the more rapid nerve regeneration
      observed after a previous (conditioning) nerve injury, adult rats were subjected
      to a midthigh sciatic nerve transection by using one of three protocols designed
      to facilitate or restrict nerve regeneration: 1) ligation, in which transected
      axons were prevented from regenerating; 2) cut, in which transected axons were
      permitted to extend into peripheral target tissue but were separated from the
      denervated peripheral nerve stump; and 3) crush, in which axons could regenerate
      normally through the denervated distal nerve tract. The affected dorsal root
      ganglia (DRG) were subsequently removed, dissociated, and cultured for up to 3
      days, and the timing of neurite initiation, rate of outgrowth, and arborization
      pattern of previously injured neurons were compared with control DRG. Our results
      indicate that conditioning lesions have at least four distinct and differentially
      regulated effects on neuronal morphogenesis: 1) conditioning lesions promote
      earlier neurite initiation, 2) prior nerve injury decreases the ability of
      neurons to extend long neurites following a second axotomy, 3) exposure to the
      environment of a denervated peripheral nerve stimulates greater initial rates of
      neurite outgrowth, and 4) conditioning lesions reduces initial neuritic branching
      frequency, resulting in straighter neurites whose growth cones extend further
      distances from their cell bodies. The primary effect of all conditioning lesions
      on cultured DRG neurons appeared to be to advance the timing of morphogenesis,
      resulting in conditioning-lesioned neurons that exhibited characteristics
      consistent with control neurons that had been cultured for an additional day or
      more. A secondary effect of conditioning lesions on neurite outgrowth rates was
      dependent on the local environment of the axons prior to culturing.

PMID- 9527539
TI  - Origin of the neurotensinergic innervation of the rat basal forebrain studied by
      retrograde transport of cholera toxin.
AB  - Basal forebrain cholinergic neurons project to the hippocampus and cerebral
      cortex where they play an important role in cortical activation, attention, and
      memory. These neurons have been shown to express functional neurotensin receptors
      and to receive a dense neurotensinergic innervation. In the present study, we
      investigated the origin of this innervation by combining retrograde transport of
      cholera toxin with immunohistochemical detection of neurotensin. After injection
      of cholera toxin in the anterior substantia innominata and diagonal band of
      Broca, retrogradely labelled cells were widely distributed throughout forebrain
      limbic structures. Only a small proportion of these cells, located (by decreasing
      order of frequency) in the lateral septum, medial preoptic area, rostral
      hypothalamus, nucleus accumbens, and rostral basal forebrain, were dually
      labelled for neurotensin. After injection of cholera toxin in the posterior
      substantia innominata and magnocellular preoptic nucleus, retrogradely labelled
      cells were detected throughout the limbic forebrain and pontomesencephalic
      tegmentum. Here again, only a small proportion of these cells, located (by
      decreasing order of frequency) in the nucleus accumbens, lateral septum, rostral
      basal forebrain, hypothalamus, bed nucleus of the stria terminalis,
      supramammilliary nucleus, ventral tegmental area, and raphe complex co-localized
      neurotensin. In view of the burst generating properties of neurotensin on basal
      forebrain cholinergic neurons, our results suggest that neurotensin projections
      may be part of the septo-hippocampo-septal loop regulating hippocampal theta
      activity. More caudally, neurotensin axons originating from the lateral
      hypothalamus and pontomesencephalic tegmentum may contribute to the contingent of
      ascending reticular formation fibers involved in the regulation of the sleep-wake
      cycle.

PMID- 9527540
TI  - Localization of glial cell line-derived neurotrophic factor receptor alpha and c
      ret mRNA in rat central nervous system.
AB  - Glial cell line-derived neurotrophic factor (GDNF) is a neurotrophic factor that
      influences the survival and function of several neuronal populations in the
      central (CNS) and peripheral nervous systems. The actions of GDNF are mediated by
      a multicomponent receptor complex composed of the tyrosine kinase product of c
      ret and the ligand-binding protein GDNF receptor alpha (GDNFR-alpha). In the
      present study, we used in situ hybridization to localize cells expressing the
      mRNA for these GDNF receptor subunits in rat CNS. As reported previously, GDNFR
      alpha and c-ret mRNA are present in the substantia nigra and ventral tegmental
      area, regions containing GDNF-responsive dopamine neurons. However, both mRNA
      were found in motor neurons of spinal cord and brainstem nuclei that innervate
      skeletal muscle. These areas include alpha motor neurons in the ventral horn of
      spinal cord and neurons in hypoglossal, facial, trigeminal, and abducens nuclei.
      In areas rostral to the substantia nigra, c-ret mRNA is not detected, whereas
      GDNFR-alpha is found in numerous brain structures, including the hippocampus,
      cortex, medial geniculate, and the medial habenula, the latter area expressing
      the highest levels of GDNFR-alpha mRNA in brain. These results provide evidence
      that c-ret and GDNFR-alpha mRNA are expressed in neuronal populations involved in
      motor function and provides further support for GDNF as a target-derived
      neurotrophic for these motor neurons. The observation that GDNFR-alpha mRNA is
      localized in several brain structures that do not contain detectable levels of c
      ret mRNA indicates that either GDNFR-alpha utilizes signal transduction molecules
      other than c-ret in these areas or that other GDNF-like ligands that utilize
      GDNFR-alpha as a receptor may be present.

PMID- 9527541
TI  - Central distribution of synaptic contacts of primary and secondary jaw muscle
      spindle afferents in the trigeminal motor nucleus of the cat.
AB  - Little is known about the differences of the terminations of group Ia and group
      II afferents within the brainstem or spinal cord. The present study was performed
      to classify cat jaw muscle spindle afferents by the use of succinylcholine (SCh)
      and to examine the morphological characteristics of the physiologically
      classified afferents at the light and electron microscopic levels through the use
      of the intra-axonal horseradish peroxidase (HRP) injection technique. The effects
      of SCh on stretch responses of 119 jaw muscle spindle afferents from the masseter
      were examined. The SCh converted the single skew distribution of the values for
      dynamic index (DI) into a bimodal one. Fifty-eight and 61 afferents were
      classified as group Ia and group II afferents, respectively. The central
      projections of 17 intra-axonally stained afferents (10 group Ia and 7 group II
      afferents) were examined. The spindle afferents terminated mainly in the
      supratrigeminal nucleus (Vsup), region h, and the dorsolateral subdivision of
      trigeminal motor nucleus (Vmo.dl) but differed in the pattern of projections of
      group Ia and group II afferents. The proportion of group Ia afferent terminals
      was higher in Vmo.dl but lower in Vsup than that of group II afferents. In
      Vmo.dl, the proportion of group Ia afferent terminals was higher in the central
      region but lower in the more outer regions than that of group II afferents. The
      ultrastructure of serially sectioned afferent boutons (63 group Ia and 72 group
      II boutons) also was examined. The boutons from the two groups were distributed
      widely from the soma to small-diameter dendrites, but the frequency of synaptic
      contacts on proximal dendrites was higher in group Ia than group II afferents.
      The present study provides evidence that the two groups of jaw muscle spindle
      afferents differ in their central projection and the spatial distribution of
      their synaptic contacts on Vmo.dl neurons.

PMID- 9527543
TI  - Ultrastructural analysis of NMDA, AMPA, and kainate receptors on unmyelinated and
      myelinated axons in the periphery.
AB  - The present study determines the proportions of unmyelinated cutaneous axons at
      the dermal-epidermal junction in glabrous skin and of myelinated and unmyelinated
      axons in the sural and medial plantar nerves that immunostain for subunits of the
      ionotropic glutamate receptors. Approximately 20% of the unmyelinated cutaneous
      axon profiles at the dermal-epidermal junction immunostain for either N-methyl-D
      aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid
      (AMPA), or kainate receptor subunits. These findings are consistent with previous
      observations that NMDA and non-NMDA antagonists ameliorate nociceptive behaviors
      that result from noxious peripheral stimulation. In the sural nerve, where the
      large majority of myelinated fibers are sensory, approximately half of the
      myelinated axon profiles immunostain for the NMDA receptor 1 (R1) subunit, 28%
      immunostain for the glutamate receptor 1 (GluR1) AMPA subunit, and 11% for the
      GluR5,6,7 kainate subunits. Even higher proportions immunostain for these
      receptors in the medial plantar nerve, a mixed sensory and motor nerve. In the
      sural nerve, 20% of the unmyelinated axon profiles immunostain for NMDAR1 and
      only 7% label for GluR1 or GluR5,6,7. Because the sural nerve innervates hairy
      skin, these data suggest that glutamate will activate a higher proportion of
      unmyelinated axons in glabrous skin than in hairy skin. Measurements of fiber
      diameters indicate that all sizes of myelinated axon profiles, including Adelta
      and Abeta, are positively labeled for the ionotropic receptors. The presence of
      glutamate receptors on large-diameter myelinated axons suggests that these
      mechanosensitive receptors, presumably transducing touch and pressure, may also
      respond to local glutamate and thus be chemosensitive.

PMID- 9527542
TI  - Time course of neuropathology in the spinal cord of G86R superoxide dismutase
      transgenic mice.
AB  - Transgenic mice with a G86R mutation in the mouse superoxide dismutase (SOD-1)
      gene, which corresponds to a mutation observed in familial amyotrophic lateral
      sclerosis (ALS), display progressive motor dysfunction leading to paralysis and
      premature death. In endstage SOD-1 transgenic mice, there is marked loss of
      spinal motor neurons and interneurons, accumulation of phosphorylated
      neurofilament inclusions, and reactive astrocytosis. The present study details
      the time course and ultrastructural appearance of these pathologic changes and
      correlates the timing of these events with the behavioral symptoms. There is no
      significant reduction in the number of total neurons, motor neurons, or
      interneurons in the ventral spinal cord of presymptomatic mice, as compared to
      age-matched control mice. In contrast, there is a significant reduction in the
      number of total neurons (-23.5%), motor neurons (-28.9%), and interneurons (
      23.5%) in symptomatic SOD-1 transgenic mice. This neuron loss correlates
      temporally with the onset of reactive astrocytosis and the appearance of
      phosphorylated neurofilament inclusions. The identical timing of motor neuron and
      interneuron degeneration in this model of ALS strongly suggests that degeneration
      in the spinal cord of patients with ALS is not specifically directed at motor
      neurons, but rather more generally at several populations of neurons in the
      spinal cord. In addition, the late onset and rapid progression of neuron loss
      suggest that a toxic property is accumulating while the SOD-1 transgenic mice are
      presymptomatic, and that this toxic property must reach a threshold level before
      the onset of neuronal degeneration.

PMID- 9527544
TI  - Postnatal localization and morphogenesis of cells expressing the dopaminergic D2
      receptor gene in rat brain: expression in non-neuronal cells.
AB  - The cellular localization of the dopaminergic D2 receptor (D2R) mRNA and protein
      was determined during postnatal development, from birth to 35 days, in the rat
      neostriatum by in situ hybridization histochemistry and immunohistochemistry. To
      localize and identify more precisely the morphology of cells expressing the D2R
      mRNA, nonradioactive, digoxigenin in situ hybridization was performed. Throughout
      this period of development, D2R mRNA and protein were widely expressed by
      neostriatal cells, adjoining forebrain cells and small cellular processes. Within
      morphologically identifiable neurons, the expression of the D2 receptor appeared
      to occur after cell division ceased. D2R gene expression appeared during neuronal
      migration and followed the developmental pattern of neuronal settling within the
      neostriatum. Both D2R mRNA and protein appeared to colocalize in neostriatal
      cells and the labeling of both appeared to accumulate within the cells
      progressively with age. The structural phenotypes of neostriatal neurons bearing
      D2R mRNA and protein were diverse throughout postnatal development. The most
      frequently stained cells were a heterogeneous group of medium spiny and aspiny
      neurons. Large cells corresponding to aspiny neurons were less frequently
      stained. Both phenotypes exhibited considerable postnatal growth of their cell
      bodies. In addition to neurons, other cell types were also observed to express
      the D2R mRNA and protein over the developmental period studied. These other cells
      included patches of ciliated ependymal cells lining the lateral ventricles and
      many interfascicular oligodendroglia of forebrain fiber tracts. These results
      demonstrate the unexpected expression of the dopaminergic D2 receptor in non
      neuronal cells within the brain. They provide a novel morphologic suggestion that
      the dopaminergic D2 receptor may support unrecognized, nonsynaptic functions in
      specific non-neuronal cell populations in the nervous system.

PMID- 9527545
TI  - Stereotyped axonal bundle formation and neuromeric patterns in embryos of a
      cyclostome, Lampetra japonica.
AB  - Early embryonic development of the nervous system of a lamprey, Lampetra
      japonica, was studied by using immunohistochemical techniques and by scanning
      electron microscopy. The earliest appearance of axons was detected at Tahara's
      stage 21-, when dorsolateral and ventral longitudinal fasciculi were present in
      the hindbrain and spinal cord regions. The branchiomeric nerve roots began to
      appear at stage 22; the fibers were joined to the dorsolateral fasciculus
      proximally and also extended distally into each pharyngeal arch. The anterior
      neural tube was divided into several neuromeres: the mid-hindbrain sulcus became
      apparent first, then the portion rostral to this sulcus was subdivided into two
      portions by the syn-parencephalic boundary. In the hindbrain around stage 23,
      rhombomeres developed transiently, of which, rhombomere 4 was the most
      distinctive. Putative crest cells forming the octavofacial nerve root anlage were
      selectively adhering to rhombomere 4, whereas no crest cells were found on
      rhombomere 3. The assignment of the crest-derived nerve anlage to rhombomeres is
      conserved between gnathostomes and L. japonica. The neuromerical scheme of the
      neural tube of L. japonica is also mostly in accordance with that in
      gnathostomes, sharing the basic developmental patterning of axon bundles at early
      developmental stages. The most distinct difference between these two groups is
      the topographical relationships between the hindbrain neuraxis and pharyngeal
      arches, as well as the otic placode.

PMID- 9527546
TI  - The Early Childhood Caries Conference. October 18-19, 1997.

PMID- 9527547
TI  - Teaching tactics.

PMID- 9527548
TI  - Misconceptions.

PMID- 9527549
TI  - No drill sergeants.

PMID- 9527550
TI  - Honest approach.

PMID- 9527551
TI  - Proceedings of the 6th Taisho International Symposium on Gastroenterology.

PMID- 9527552
TI  - Kinetic versus endpoint measurement for quantitative histochemical determination
      of enzyme activity in muscle fibers.

PMID- 9527553
TI  - Immunohistochemical detection of parathyroid hormone-related protein in human
      astrocytomas.

PMID- 9527554
TI  - [Imaging diagnosis of cancer of the nasopharynx-- CT and MRI findings].

PMID- 9527555
TI  - A comparison of the site-specificity of supragingival and subgingival calculus
      deposition.
AB  - The aims of the present study on 40 patients were to quantitate by the Volpe
      Manhold method, the amount of supragingival (SPR) calculus, to determine
      qualitatively the amount of subgingival calculus (SBG), and to determine the
      association between supragingival and subgingival calculus on vestibular and
      lingual surfaces of all the teeth except third molars. Kappa values for
      intraexaminer reproducibility varied between 0.863 and 0.738. There was marked
      site-specificity of SPR calculus scores, with the highest values by far on the
      lingual aspects of the lower anterior teeth: central incisor, lateral incisor,
      and canine, respectively. Although the grades for SBG calculus were higher on the
      lingual surfaces than on the vestibular surfaces of 25 of the 28 teeth, there was
      much less site-specificity than for SPR calculus. For the teeth as a whole, there
      were significant associations (P < 0.001), as tested by chi-square or Fisher's
      exact test, between SPR and SBG grades on both vestibular and lingual surfaces,
      between SPR grades on vestibular and lingual surfaces, and between SBG grades on
      vestibular and lingual surfaces. However, for individual teeth, or groups of
      similar teeth, only a few of the above associations were statistically
      significant.

PMID- 9527556
TI  - Effects of expanded polytetrafluoroethylene and polylactic acid barriers on
      healthy sites.
AB  - The configuration of the barrier devices to treat interproximal defects by guided
      tissue regeneration (GTR) necessitates inclusion of healthy adjacent teeth to
      secure the barriers in place. The purpose of this study was to evaluate the
      effects of expanded polytetrafluoroethylene (ePTFE) and polylactic acid (PLA)
      barrier devices on probing depth (PD), clinical attachment level (CAL), and
      crestal bone height in healthy sites. The study included 30 patients who were in
      an earlier study which compared the effects of GTR utilizing an ePTFE or a PLA
      barrier in intrabony defects. Thirty defects were randomly assigned to receive
      either a PLA (test) or an ePTFE barrier (control) after open flap debridement.
      The sites in this investigation included those healthy sites in the immediately
      adjacent non-affected teeth covered by the barriers. CAL and PD were measured at
      baseline and 12 months. Intrasurgical crestal bone height was recorded at the
      time of barrier placement and at a 12-month re-entry. Two-sample t-test
      comparisons of PD and CAL measurements between barrier device covered sites at
      baseline (PD: ePTFE, 2.32+/-0.51; PLA, 2.59+/-0.74; CAL: ePTFE, 2.71+/-0.66; PLA,
      2.59+/-0.65 mm), and at one year (PD: ePTFE, 2.14+/-0.37; PLA, 2.07+/-0.56; CAL:
      ePTFE, 3.14+/-1.05; PLA, 2.75+/-0.73 mm) were not statistically different (P >
      0.05). Paired t-test was utilized to compare changes in PD, CAL, and crestal bone
      height from baseline to 12 months. A statistically significant reduction in PD
      was found in the PLA group (delta = -0.52, P = 0.01) while no significant change
      was found in the ePTFE group (delta = -0.18, P = 0.18). Change in CAL was
      statistically significant in the ePTFE group (delta = 0.43, P = 0.02) while no
      significant change was found in the PLA group (delta = 0.16, P = 0.39). Crestal
      bone height changes from baseline to 12 months were statistically different for
      both groups (ePTFE, delta = 0.8 mm, P = 0.001; PLA, delta = 0.6 mm, P = 0.001).
      These resorptive changes, when compared between treatment groups were not
      statistically different (P > 0.05). In conclusion, the placement of ePTFE or PLA
      barriers on healthy sites resulted in probing depth reductions and loss of
      attachment of 0.5 mm or less. Additionally, both groups exhibited less than 1.0
      mm of crestal bone resorption.

PMID- 9527557
TI  - Clinical evaluation of electronic and manual constant force probes.
AB  - The objective of this study was to compare the measurements of an electronic
      controlled-force probe (FP) to that of a manual controlled-force probe (SP) and a
      conventional probe (CP). Twelve subjects were recruited. A quadrant with no
      missing teeth (excluding third molars) was selected. Probing depth was measured
      at 6 sites per tooth (mesiobuccal, buccal, distobuccal, mesiolingual, lingual,
      and distolingual) by two examiners (AK and KC) each using the three probes in the
      following sequence: FP, SP, and CP. The same measurements were repeated a week
      later by both examiners. The mean difference of measurements between CP and FP
      was 0.375 +/- 0.858 mm (P < 0.05), with 52.7% of the measurements within 0.5 mm
      and 80% within 1.0 mm. Correlation between measurements was high (0.7208) and
      significant (P < 0.001). The mean difference between SP and FP was 0.450 +/-
      0.863 mm (P < 0.05), with 49.1% of the measurements within 0.5 mm and 76.9%
      within 1.0 mm. Correlation between measurements was high (0.7354) and significant
      (P < 0.001). The mean difference between CP and SP was -0.074 +/- 0.373 mm (P <
      0.05), with 49.1% of the measurements within 0.5 mm and 76.9% within 1.0 mm.
      Correlation between measurements was high (0.95) and significant (P < 0.001).
      Intra-examiner differences varied for each examiner. For both examiners, the
      correlations for FP (AK = 0.77, KC = 0.46) were lower than that for CP (AK =
      0.86, KC = 0.80) and SP (AK = 0.86, KC = 0.83). Inter-examiner comparisons showed
      that the correlation for FP (0.50) was lower than that for CP (0.85) and SP
      (0.86). The percentage of sites within 1 mm differences was less for FP (70%)
      than for CP (94%) or SP (94%). In conclusion, both CP and SP correlated well with
      FP. None of the three probes investigated completely eliminated probing errors.
      The CP and SP yielded more reproducible measurements than FP. Regardless of the
      type of probe used, probing measurements are subject to both intra- and
      interexaminer errors.

PMID- 9527558
TI  - Periodontal repair in dogs: effect of allogenic freeze-dried demineralized bone
      matrix implants on alveolar bone and cementum regeneration.
AB  - The objective of this study was to evaluate alveolar bone and cementum
      regeneration following surgical placement of an allogenic, freeze-dried,
      demineralized bone matrix (DBM) cortical strip implant. Critical size,
      supraalveolar periodontal defects were surgically created around the second,
      third, and fourth mandibular premolar teeth in eight mongrel dogs. Contralateral
      jaw quadrants in six animals were randomly assigned to receive the DBM implant,
      or serve as surgical control. Two additional animals received bilateral DBM
      implants. Flaps were coronally advanced to submerge teeth and implants, and
      sutured. Three animals were exited from the study due to extensive early wound
      failure. Remaining animals were sacrificed at 8 weeks postsurgery. Histometric
      recordings included defect height, bone regeneration/DBM implant height, cementum
      regeneration height, root resorption, and ankylosis. Large areas of unresorbed
      DBM exhibiting fragmentation and empty osteocyte lacunae were observed adjacent
      to new bone formation, or bone formation was observed adjacent to or within the
      implant, often exhibiting ankylosis. Cementum regeneration appeared enhanced in
      shelter of the DBM implant. Histometric recordings (mean+/-SD) for DBM and
      control defects, respectively, were: defect height, 4.8+/-0.2 mm and 4.4+/-0.2
      mm; bone regeneration/DBM implant height, 4.0+/-1.3 mm and 1.2+/-0.6 mm; cementum
      regeneration height, 1.4+/-0.4 mm and 0.7+/-0.2 mm; root resorption, 0.5+/-0.3 mm
      and 1.2+/-0.3 mm; and ankylosis, 0.5+/-0.2 mm and 0.1+/-0.1 mm without
      statistically significant differences between experimental conditions (N=3).
      Within the limitations of this study, the histologic observations suggest that
      surgical implantation of allogenic, freeze-dried DBM cortical strip implants may
      have a potential to support cementum regeneration, possibly by providing
      conditions for guided tissue regeneration, however, alveolar regeneration appears
      unpredictable.

PMID- 9527559
TI  - The expression of collagen I and XII mRNAs in Porphyromonas gingivalis-induced
      periodontitis in rats: the effect of doxycycline and chemically modified
      tetracycline.
AB  - Tissue remodeling is a dynamic state in which a balance is achieved between the
      proteolytic breakdown and synthesis of the extracellular matrix. Type I collagen
      is a major component of the gingival connective tissue (GCT) and the periodontal
      ligament (PDL) throughout development, while type XII collagen has been found in
      the mature forms of these tissues. The purpose of this study was to investigate
      the effects of periodontitis on the expression of type I and XII collagen and
      subsequently to investigate the effects of doxycycline (DOXY) and chemically
      modified non-antimicrobial tetracycline (CMT-1) on the expression of these
      molecules in this model. Adult barrier-raised male Sprague-Dawley rats were
      inoculated with Porphyromonas gingivalis obtained from humans to create the
      experimental periodontitis. The animals with the P. gingivalis-induced
      periodontitis were then split into the following groups: Group A served as
      infected untreated controls (PGI group); group B was treated with doxycycline
      (DOXY group); and group C was treated with chemically modified tetracycline-1
      (CMT-1 group). Group D contained uninfected animals that served as uninfected
      controls (NIC group). The expression of type I and XII collagen mRNAs was
      examined by in situ hybridization in each group, with the co-expression of these
      molecules representing mature and functional gingival connective tissue. In the
      NIC group, cells hybridized with digoxygenine-labeled cDNA probes encoding rat
      alpha2(I) or alpha1(XII) collagens were found distributed uniformly throughout
      the periodontal connective tissue. The PGI group showed little hybridization in
      the areas of infection, while both the DOXY and CMT-1 groups showed co-expression
      of the alpha2(I) and alpha1(XII) probes in the GCT and coronal part of the PDL.
      This study demonstrates that doxycycline and CMT-1 moderate or reduce the
      inhibitory effects of periodontal infection on the expression of type I and type
      XII collagen mRNAs. These results suggest that doxycycline and a form of non
      antimicrobial tetracycline, chemically modified tetracycline-1, can reduce
      periodontal destruction by reversing the inhibitory effect of periodontal
      infection on collagen synthesis.

PMID- 9527560
TI  - Effects of repeated hand instrumentation on the marginal portion of a cast gold
      crown.
AB  - A study was conducted to evaluate the effects of repeated hand instrumentation on
      the marginal portion of a cast gold crown. Seven extracted periodontally diseased
      premolars were used. The finishing line of the preparation was placed on the root
      surface and then the crown was cast and cemented in the usual manner. One
      proximal surface of each sample was divided into 2 areas: root planing (RP) area
      and RP plus polishing (RPP) area. The marginal portion of the crown was measured
      to give a baseline value using a surface roughness- and profile-analyzing system.
      Then, the marginal portion was painted with a waterproof pen. RP was performed to
      remove paint in the RP area with the curets. In the RPP area, RP followed by
      polishing was done by silicone polishing points and a rubber cup with polishing
      paste. The relevant procedures and measurements were repeated 3 times in each
      area. Changes in the sample roughness and profile were evaluated and compared
      between the 2 techniques. The results showed that repeated instrumentation
      altered the surface of the marginal portion of the cast gold crown, resulting in
      increased roughness in both areas (P < 0.01). However, the roughness of the RPP
      area was considerably restored to the baseline value by polishing after RP.
      Therefore, it is suggested that polishing after RP smoothes the marginal portion
      of the cast gold crowns and appears to be an efficient prophylactic system.

PMID- 9527561
TI  - Long-term maintenance of alveolar bone gain after implantation of autolyzed,
      antigen-extracted, allogenic bone in periodontal intraosseous defects.
AB  - This randomized controlled trial assessed the long-term maintenance of alveolar
      bone gain after implantation of autolyzed, antigen-extracted, allogenic (AAA)
      bone. AAA bone is a demineralized freeze-dried bone allograft processed after
      previously described methods. In each of 14 patients, AAA bone was implanted into
      the intraosseous defect of 1 tooth (test); a second tooth with an intraosseous
      defect was treated by modified Widman flap surgery alone (control). All patients
      were offered supportive periodontal therapy at 3- to 6-month intervals following
      treatment. Clinical measurements were taken prior to surgery, 6 months, and 3
      years following surgery. Of the 14 patients enrolled, 11 patients completed the 6
      month and 8 patients the 3-year examination. In test teeth, bone gain was
      significantly greater compared to control teeth at 6 months (2.2+/-0.5 mm and
      1.2+/-0.5 mm, respectively) and 3 years (2.3+/-0.7 mm and 1.1+/-0.8 mm,
      respectively) (P < 0.05). Also, more probing attachment was gained in test
      compared to control teeth at 3 years (2.0+/-0.7 mm and 0.8+/-0.5 mm,
      respectively; P < 0.05). At 3 years, Porphyromonas gingivalis was detected in 3
      test and 2 control teeth by polymerase chain reaction, whereas no Actinobacillus
      actinomycetemcomitans was found. Due to the low detection frequency, there was no
      clear correlation between the maintenance of alveolar bone during supportive
      periodontal therapy and subgingival infection with P. gingivalis. The data
      indicated that alveolar bone gain after implantation of AAA bone may be
      maintained over a minimum of 3 years in patients receiving periodontal supportive
      therapy.

PMID- 9527562
TI  - Histologic evaluation of guided tissue regeneration using 4 barrier membranes: a
      comparative furcation study in dogs.
AB  - This study evaluated and compared four different barrier membrane materials used
      to treat class II mandibular premolar and molar furcations in seven dogs with
      naturally occurring periodontitis. Five class II furcation defects in each animal
      were randomly assigned to one of four experimental groups or to a control group.
      Each defect was treated by surgical debridement, root planing, and barrier
      membrane coverage with one of the four test materials or no barrier membrane
      (control). Thus, each animal served as its own control. Following 6 months of
      healing, block sections were used to histologically measure the amount of
      regenerated tissue and stereometrically enumerate the inflammatory cell
      infiltration observed with each of the treatment modalities. The four barrier
      membrane materials (polycarbonate filter, silicone rubber, expanded
      polytetrafluoroethylene, and polycaprolactone) all provided a wound healing
      environment that promoted new cementum formation, with mean values ranging from
      1.96 +/- 0.031 mm to 2.18 +/- 0.015 mm, and facilitated alveolar bone
      regeneration, with mean values ranging from 1.18 +/- 0.019 mm to 1.44 +/- 0.014
      mm. Control-treated sites showed mean values of only 0.24 +/- 0.007 mm new
      cementum formation and 0.32 +/- 0.017 mm bone fill. Polycarbonate filter and
      polycaprolactone membrane barriers elicited a significantly greater chronic
      inflammatory cell response of lymphocyte and plasma cell infiltrates as compared
      to expanded polytetrafluoroethylene and silicone rubber, which were comparable to
      control-treated sites.

PMID- 9527564
TI  - Genotypic characterization of Actinobacillus actinomycetemcomitans isolated from
      periodontitis patients by arbitrarily primed polymerase chain reaction.
AB  - Actinobacillus actinomycetemcomitans is one of the most suspected pathogens in
      the initiation and progression of juvenile periodontitis and severe adult
      periodontitis. The aim of the present study was to investigate the genotypic
      characterization of A. actinomycetemcomitans using arbitrarily primed polymerase
      chain reaction (AP-PCR). AP-PCR was applied to 143 A. actinomycetemcomitans
      strains, including 8 reference strains and 135 clinical strains isolated from 43
      unrelated Japanese periodontitis patients. The DNA fragment patterns obtained
      using a single 10-mer primer with random sequence (OPA-07) for these strains
      allowed the recognition of 10 distinct AP-PCR groups that correlated to some
      extent with serotypes. AP-PCR group VIII was significantly (P < 0.05) observed in
      deep (> 5 mm) periodontal pockets. Group II was exclusively detected in deep
      pockets. However, a clear relationship was not observed between AP-PCR genotypes
      and various periodontal status. Only one genotype was found within individual
      oral cavity/single-infected site, except one case in which the patient harbored
      two AP-PCR genotypes. The AP-PCR patterns of the A. actinomycetemcomitans
      isolates recovered from the site after periodontal treatment remained identical.
      These results demonstrate genetic diversity among the investigated population and
      a clonal nature in a periodontal patient of A. actinomycetemcomitans by AP-PCR.
      Furthermore, it could be inferred that a certain AP-PCR genotype(s) of A.
      actinomycetemcomitans is more important in the pathogenesis of periodontal
      diseases.

PMID- 9527563
TI  - An immunocytochemical study for lysosomal cathepsins B and D related to the
      intracellular degradation of titanium at the bone-titanium interface.
AB  - The morphological relationship between titanium and lysosomal proteinases,
      cathepsins B and D, at the bone-titanium interface using titanium-coated plastic
      implants placed for 28 days in the tibiae of 6-week-old rats was
      immunocytochemically investigated by the colloidal immunogold-silver method.
      Under light microscopy the titanium layer appeared to make direct contact with
      the bone and one or a few layers of slender cells were interposed between the
      bone and titanium. Ultrastructurally, the titanium came in contact with the bone
      or the slender cell layer through a 20 to 40 nm thin amorphous zone. The slender
      cells at the bone-titanium interface consisted of two types; one was an
      osteoblast type with glycogen granules which was found along the newly-formed
      bone facing titanium layer. The other was a fibroblast type which came in contact
      with the titanium layer and occasionally endocytosed the detached titanium
      fragments. In addition, some of the slender cells also showed degenerative
      changes. Immunocytochemically, cathepsins B and/or D were sometimes colocalized
      in some phagolysosomes with titanium fragments. These findings suggested that the
      fibroblast types at the bone-titanium interface may act as scavengers to remove
      both cell debris and titanium by means of some endocytotic ability, and lysosomal
      cathepsins also developed in response to the endocytosed titanium. The osteoblast
      type also appears to show a high degree of osteogenic activity around the
      titanium-coated plastic implants.

PMID- 9527565
TI  - Non-insulin dependent diabetes mellitus and alveolar bone loss progression over 2
      years.
AB  - This study tested the hypothesis that persons with non-insulin dependent diabetes
      mellitus (NIDDM) have greater risk of more severe alveolar bone loss progression
      over a 2-year period than those without NIDDM. Data from the longitudinal study
      of the oral health of residents of the Gila River Indian Community were analyzed
      for 362 subjects, aged 15 to 57, 338 of whom had less than 25% radiographic bone
      loss at baseline, and who did not develop NIDDM nor lose any teeth during the 2
      year study period. The other 24 subjects had NIDDM at baseline, but met the other
      selection criteria. Bone scores (scale 0-4) from panoramic radiographs
      corresponded to bone loss of 0%, 1%-24%, 25%-49%, 50%-74%, or 75% and greater.
      Change in bone score category was computed as the change in worst bone score
      (WBS) reading after 2 years. Age, calculus, NIDDM status, time to follow-up
      examination, and baseline WBS were explanatory variables in regression models for
      ordinal categorical response variables. NIDDM was positively associated with the
      probability of a change in bone score when the covariates were controlled. The
      cumulative odds ratio for NIDDM at each threshold of the ordered response was
      4.23 (95% C.I. = 1.80, 9.92). In addition to being associated with the incidence
      of alveolar bone loss (as demonstrated in previous studies), these results
      suggest an NIDDM-associated increased rate of alveolar bone loss progression.

PMID- 9527566
TI  - Immunocytochemical discrimination between early and late S phase: a new approach
      to the study of gingival epithelium proliferation in rats.
AB  - The renewal of the free gingival margin epithelium in rats was studied evaluating
      5-bromodeoxyuridine (BrdU) incorporation in proliferating cells by means of an
      immunocytochemical method. We found a close correspondence between light and
      electron microscopy patterns of BrdU incorporation at a nuclear level. BrdU was
      localized in the inner interchromatin regions in cells starting DNA synthesis,
      while it was localized in the peripheral heterochromatin domains in cells
      terminating the S phase. This possibility of discriminating cells in early S
      phase from cells in late S is able to provide far more information as to the time
      at which a labeled cell starts proliferation than that obtainable with 3H
      thymidine autoradiography. This, in turn, permits detection of cells that start
      proliferation in a wide period of time by means of a single BrdU administration.
      Rats treated at 7 a.m. demonstrated higher proliferation than rats treated at 7
      p.m., supporting the existence of circadian variations in the epithelial renewal.
      Proliferative events take place by consecutive activation of at least three
      replication waves, producing clusters of labeled cells which could be observed in
      rats sacrificed at 10 a.m. In rats treated once with BrdU at 7 a.m., the clusters
      were localized in both the basal and suprabasal layer of the epithelium; in rats
      further injected with BrdU at the same time, the clusters increased in size,
      progressively extending throughout the epithelium. In this way, the renewal of
      the free gingival margin epithelium does not proceed randomly, but by consecutive
      activation of discrete units or clusters of basal cells, which then extend to the
      upper layers. This can be followed at a morphological level as a progression of
      labeled cells, which move from the basal layer to the epithelium surface in
      approximately 82-85 hours.

PMID- 9527567
TI  - A comparison of 2 patient populations using fractal analysis.
AB  - This study was undertaken to demonstrate that the fractal dimensions calculated
      using digitized non-standardized, clinical radiographs of mandibular alveolar
      bone from a population of patients diagnosed with periodontitis are statistically
      different from fractal dimensions calculated from another population diagnosed as
      having gingivitis or healthy gingiva. The fractal dimension was calculated using
      a public domain fractal analysis program distributed by the National Institutes
      of Health (NIH). Fractal dimensions were calculated from digitized clinical
      radiographs for 29 patients diagnosed with healthy gingiva and/or gingivitis and
      32 patients diagnosed with periodontitis and compared. To estimate the
      reproducibility of the technique, we recalculated the fractal dimension from
      images of the gingivitis patients 3 months after the original calculations and
      compared them to the originals. A 2 sample, 2-tailed Student t test showed the
      gingivitis data group to be different from the periodontitis data group (P =
      0.0012). The original gingivitis and repeat gingivitis groups fractal dimension
      calculation were the same and analysis showed the two data sets were not
      significantly different (P = 0.99). We found that: 1) fractal dimensions could be
      used to distinguish between gingivitis and periodontitis patient groups; 2)
      fractal dimensions could be calculated from non-standardized clinical
      radiographs; and 3) fractal dimensions for gingivitis patients were reproducible
      over a 3-month period.

PMID- 9527568
TI  - Subgingival distribution of periodontopathic bacteria in adult periodontitis and
      their susceptibility to minocycline-HCl.
AB  - The purpose of this study was to investigate the distribution of several
      periodontopathic bacteria in adult periodontitis, their in vitro susceptibility
      to minocycline-HCl, and whether the efficacy of the drug changes with a decrease
      in bacterial susceptibility. Twenty-one patients (43 to 75 years old) with 62
      periodontal lesions from pockets > or =4 mm participated in the study. After
      subgingival sampling, an ointment containing 2% minocycline-HCl was applied
      locally to the selected pockets once a week for 4 weeks. The lesions were
      clinically examined after 1 and 4 weeks of administration. The distribution of
      the subgingival microorganisms included Capnocytophaga sputigena (37.1%),
      Prevotella intermedia (22.6%), Porphyromonas gingivalis (22.6%), Fusobacterium
      nucleatum (20.1%), Actinobacillus actinomycetemcomitans (9.7%), and Eikenella
      corrodens (4.8%). The distribution was complex, with 76.8% of the sites
      containing 1 to 3 bacterial spieces. The minimum inhibitory concentration (MIC)
      of minocycline-HCl for each organism showed that most were inhibited by a
      minocycline-HCl concentration equal to or less than the MIC for reference
      strains. However, some clinical strains of Prevotella intermedia seemed to
      exihibit low susceptibility to minocycline-HCl. There were no significant
      differences among sites with strains exhibiting low or normal susceptibility to
      minocycline-HCl. The concentration of the drug applied to deep periodontal
      pockets inhibited the growth of most of the microorganisms investigated in this
      study.

PMID- 9527569
TI  - Power Doppler sonography in tenosynovitis: significance of the peritendinous
      hypoechoic rim.
AB  - The aim of this study was to evaluate the ability of power Doppler sonography to
      distinguish between hypoechoic fluid and synovium in patients with suspected
      tenosynovitis. Gray scale sonography and power Doppler sonography were performed
      on 26 tendons in 24 patients with tenosynovitis and 30 tendons in five
      asymptomatic volunteers. Peritendinous blood flow was graded on a scale of 0 to 3
      and the percentage of the hypoechoic rim that contained blood flow was also
      noted. In the symptomatic group, flow was demonstrated in more than 50% of the
      peritendinous hypoechoic rim in 17 of 26 tendons. A positive correlation was
      found between the power Doppler sonographic grade and the percentage of the rim
      that had flow. These results suggest that a significant proportion of the
      hypoechoic rim probably represents vascularized synovium rather than complex
      fluid.

PMID- 9527570
TI  - Evaluation of palpable breast masses with color Doppler sonography and gray scale
      imaging.
AB  - Excisional biopsy is the standard method of distinguishing benign from malignant
      masses of the breast. However, alternative, less invasive methods of diagnosis
      are needed to reduce the number of unnecessary biopsies, allay anxiety of the
      patient, and control costs. In this study, we evaluated breast masses in a series
      of patients using color Doppler sonography and gray scale ultrasonographic
      features. In all cases, the pathologic diagnosis of the breast mass was
      subsequently established by excisional biopsy. The accuracy of gray scale
      sonography exceeded that of color Doppler sonography at a significance level of P
      < 0.005.

PMID- 9527571
TI  - Paraspinal ultrasonography: lack of accuracy in evaluating patients with cervical
      or lumbar back pain.
AB  - This study evaluates the ability of paraspinal ultrasonography to identify
      abnormal echogenicity in patients with cervical or lumbar back pain, or both.
      Paraspinal ultrasonography was performed on 82 subjects, including 23
      asymptomatic controls. Echogenicity in the region of nerve roots and facets was
      assessed. Readings were correlated with location of patients' symptoms, if any.
      Receiver operating characteristic analysis demonstrated that evaluation of nerve
      roots by all four readers did not differ significantly from chance (0.07 < P <
      0.99). Specificities ranged from 0 to 0.68. Kappa values were 0.06 for cervical
      and -0.06 for lumbar spine. Ultrasonography was unable to demonstrate abnormal
      echogenicity adjacent to facets in symptomatic patients. Paraspinal
      ultrasonography is neither accurate nor reproducible in evaluating patients with
      cervical and lumbar back pain.

PMID- 9527572
TI  - Color Doppler sonographic detection of tumor flow in superficial melanoma
      metastases: histologic correlation.
AB  - Color Doppler sonographic detection of tumor flow within superficial melanoma
      metastases was investigated to determine if tumor size, vessel size, or vessel
      number influences signal detection. Color Doppler imaging of 32 pathologically
      proved melanoma metastases was performed at 6 MHz with color Doppler imaging
      parameters optimized for each lesion scanned. All lesions were measured in three
      dimensions and the presence or absence of internal flow was documented. Seven
      surgically excised metastases underwent immunohistochemical staining for
      endothelial markers. Internal flow was detected in 21 of 32 masses and was
      completely absent in 11. In comparison to all masses without flow, the masses
      with flow had significantly greater anteroposterior dimensions (P < 0.00036) and
      volumes (P < 0.01). Histologically, mean vessel diameter in masses with flow was
      significantly greater (P < 0.05) than in those without flow, but mean vessel
      number was not significantly different. In conclusion, detectability of tumor
      blood flow in superficial melanoma metastasis may be related more to tumor size
      and vessel size than vessel number. Failure to detect color signal within a
      superficial melanoma mass does not indicate a lack of internal vascularity.

PMID- 9527573
TI  - Significance of an echogenic intracardiac focus in fetuses at high and low risk
      for aneuploidy.
AB  - Our objective was to evaluate the significance of an echogenic intracardiac focus
      in a mixed population of fetuses at high and low risk for aneuploidy. Over a 1
      year period, we prospectively identified all fetuses with an echogenic
      intracardiac focus seen during prenatal sonography. A detailed structural
      evaluation was performed on each fetus as permitted by gestational age. The
      location and number of foci were tabulated prospectively, as were associated
      abnormalities. Follow-up was obtained by review of the medical record. Of the 290
      fetuses who had an echogenic intracardiac focus, 14 of them were aneuploid
      (4.8%). Of the 290 mothers, 125 women were aged 35 years or older and 165 women
      were younger than 35 years old. Among the 125 fetuses born to women 35 years or
      older, eight were aneuploid fetuses (6.4%), while among the 165 fetuses of
      younger mothers, six were aneuploid fetuses (3.6%) (rate ratio = 1.8; 95%
      confidence interval [extremes] = 0.6, 4.9). Only one of the 14 aneuploid fetuses
      had an echogenic intracardiac focus as the only sonographic finding, and this
      occurred in a woman aged 41 years. The majority of the echogenic intracardiac
      foci (87.6%) were located in the left ventricle, while 4.8% of the foci were
      right-sided and 7.6% were bilateral. Among the 14 aneuploid fetuses, 14% had
      bilateral echogenic intracardiac foci and 7% had right-sided foci. Among the
      euploid fetuses, 7.3% had bilateral echogenic intracardiac foci and 4.7% had
      right-sided foci. In conclusion, we have shown that the presence of an echogenic
      intracardiac focus does raise the risk that the fetus has a chromosomal
      abnormality, most commonly Down syndrome, although all but one aneuploid fetus in
      our study had other sonographic findings.

PMID- 9527574
TI  - Effect of regular aerobic exercise on cerebrovascular tone in young women.
AB  - Our objective was to evaluate the effect of regular aerobic exercise on
      cerebrovascular tone in young women. Color and pulsed Doppler ultrasonography
      were used to determine the pulsatility index in the ophthalmic artery in 20
      normotensive, nonpregnant young women (aged 19 to 26 years) with a regular
      menstrual cycle on cycle day 5. Blood pressure and heart rate were recorded at
      each examination. Blood samples were collected from all the subjects to measure
      serum estradiol levels and serum lipid profiles. Ten of the 20 women (exercise
      group) have maintained aerobic exercise for 50 min, 3 to 5 days a week, for at
      least a year. The other 10 women (nonexercise group) never did regular exercise.
      There were no significant differences between the two groups regarding age, body
      mass index, mean blood pressure, and heart rate and serum estradiol, total
      cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein
      cholesterol, and triglyceride levels. The pulsatility index value (mean, 1.89;
      standard deviation, 0.33) of the ophthalmic artery in the exercise group was
      significantly lower than that (mean, 2.53; standard deviation, 0.26) in the
      nonexercise group. Regular aerobic exercise in young women significantly
      decreases the peripheral cerebrovascular tone, and this might be a favorable
      adaptation for early prevention of cerebrovascular disease, which is common in
      older women.

PMID- 9527575
TI  - Visualization of fetal genitalia by three-dimensional ultrasonography in the
      second and third trimesters.

PMID- 9527576
TI  - Assessment of fetal and placental blood flow in primates using contrast enhanced
      ultrasonography.
AB  - Ultrasonographic contrast agents that stay within the vascular space and do not
      cross the placenta may permit differentiation between the maternal and fetal
      portions of the placenta and may be clinically useful for diagnosis of placental
      abnormalities. This study was performed to assess the effects of Levovist
      (Schering AG, Berlin) on the placental circulation and to determine whether
      hemodynamic effects on the fetus occur. Ten studies were performed in five
      pregnant macaques (median weight, 9.15 kg; range, 6.15 to 11 kg; median
      gestational age, 121 days; range, 34 days to term) under anesthesia. Gray scale,
      color, and duplex Doppler sonographic scans of the fetus and placenta were
      acquired using a 5 MHz curved array transducer. Fetal heart rate, resistive
      index, and systolic-diastolic ratios were measured in the fetal middle cerebral
      artery, aorta, umbilical artery, and uterine artery before and after
      administration of contrast agent. The following dose regimen was tested: 5 ml of
      physiologic saline solution followed by 0.1 ml/kg of 300 mg/ml Levovist
      (diagnostic dose), 0.5 ml/kg of 400 mg/ml Levovist (maximum dose), and 5 ml
      physiologic saline solution. The order of diagnostic dose and maximal dose was
      randomized among animals. Color enhancement of the basal portions of the placenta
      was documented after administration of contrast agent. Heart rate and middle
      cerebral artery systolic-diastolic ratio did not change between baseline and
      injections. A 7% decrease of the resistive index from baseline to maximum dose
      was measured in the uterine artery (not significant). A 7.7% decrease in the
      systolic-diastolic ratio from baseline to maximum dose was recorded in the
      umbilical artery. However, an identical change was measured after saline solution
      was injected. The resistive index in the aorta increased by 2.6% from baseline to
      maximum dose, a change that was not significant (P > 0.5). Ultrasonographic
      contrast enhancement of the maternal circulation in placenta is demonstrated to
      be without significant effects on the fetal circulation as measured in this
      limited population.

PMID- 9527577
TI  - Diagnosis of ovarian torsion with color Doppler sonography: depiction of twisted
      vascular pedicle.
AB  - The purpose of this study was to assess the diagnostic value of ultrasonography
      for the detection of twisted vascular pedicle in ovarian torsion and to verify
      whether the blood flow alterations in the twisted vascular pedicle on color
      Doppler sonography can predict the viability of adnexal structures. In 28 of 32
      patients with surgically proved torsion, the twisted vascular pedicle was
      detected preoperatively by ultrasonography, which shows a diagnostic accuracy of
      87%. Arterial and venous flows were present in the twisted vessels on color
      Doppler sonography in 16 of 28 patients with a visible twisted vascular pedicle.
      In 11 patients who underwent adnexectomy, the pathologic findings revealed
      nonnecrotic ovaries in 10 patients. Untwisting of the twisted vascular pedicle
      was performed in five patients, and follow-up ultrasonography showed normal
      follicular development and ovulation. All 12 patients who showed no blood flow
      within the twisted vascular pedicle had necrotic ovaries. In conclusion,
      identification of the twisted vascular pedicle through ultrasonography is
      suggestive of ovarian torsion, and color Doppler sonography could be helpful in
      predicting the viability of adnexal structures by depicting blood flow within the
      twisted vascular pedicle.

PMID- 9527578
TI  - Comparison of transcranial power Doppler and contrast-enhanced color-coded
      sonography in the identification of intracranial arteries.
AB  - Power-based transcranial color-coded sonography and contrast-enhanced
      transcranial color-coded sonography are ultrasonographic techniques that allow
      improved visualization of vascular structures. The present study was designed to
      investigate and compare the diagnostic capacity and applicability of both methods
      in the assessment of intracranial vessels of the circle of Willis (33 patients)
      and the vertebrobasilar system (21 patients). Compared to conventional
      transcranial color-coded sonography, both power-based and contrast-enhanced
      transcranial color-coded sonography improved the diagnostic sensitivity in
      identifying peripheral segments and small vessels of the circle of Willis.
      Contrast-enhanced transcranial color-coded sonography was significantly superior
      to power-based transcranial color-coded ultrasonography in the depiction of the
      second segment of the middle cerebral artery (66 of 66 versus 60 of 66, P <
      0.005), both segments of the anterior cerebral artery (66 of 66 versus 56 of 66
      for the A1 segment, P < 0.005; 61 of 66 versus 44 of 66 for the A2 segment, P <
      0.005), the first segment of the posterior cerebral artery (66 of 66 versus 55 of
      66, P < 0.005), and the basilar artery using the transtemporal approach (21 of 21
      versus 15 of 21, P < 0.05). Using the transforaminal approach contrast-enhanced
      transcranial color-coded real-time sonography did not increase fine resolution of
      the vertebrobasilar system compared to power Doppler sonography. In conclusion,
      contrast-enhanced transcranial color-coded real-time sonography further improves
      the diagnostic potential of power Doppler sonography in the identification of
      vascular structures of the circle of Willis. Contrast-enhanced transcranial color
      coded sonography and power Doppler sonography are equally effective in
      visualizing the vertebrobasilar system with branches.

PMID- 9527580
TI  - Intensive Care Nephrology. Proceedings of the 1st International Course on
      Critical Care Nephrology. Dresden, Germany, May 2-3, 1997.

PMID- 9527579
TI  - Do ultrasonic contrast agents artificially increase maximum Doppler shift? In
      vivo study of human common carotid arteries.
AB  - The aim of this study was to establish whether an increase of maximum Doppler
      shift occurs in the human common carotid artery after the administration of
      Levovist, an ultrasonographic echo enhancer. Twenty common carotid arteries of 10
      patients were examined. Spectral Doppler waveform examinations were performed
      before and after administration of Levovist using an Acuson 128 XP 10 and a 7.0
      MHz transducer probe. Time averaged mean velocity, peak velocity, maximum Doppler
      shift, and spectral Doppler indices (pulsatility index, resistive index, systolic
      diastolic ratio) were assessed. No significant changes in any of the measured
      parameters, including maximum Doppler shifts, peak velocity (P = 0.35, Wilcoxon
      rank sum test), pulsatility indices (P = 0.70), resistive indices (P = 0.98), or
      other spectral indices, were found. We conclude that an increase in Doppler shift
      does not inevitably occur after the administration of a signal enhancer when
      examining the human common carotid artery.

PMID- 9527581
TI  - [Vision loss as the initial symptom of Creutzfeldt-Jakob disease].

PMID- 9527582
TI  - [Ophthalmological information services on the internet--an analysis of user
      hits].

PMID- 9527583
TI  - [Visual field examination in limited patient cooperation].
AB  - Objective methods to estimate the visual field are necessary, if a conventional
      subjective perimetry is impossible due to limited cooperation. Objective methods
      are indicated in infants, handicapped patients, patients with psychogenic visual
      field loss, and malingerers. An objective estimation of the visual field can be
      performed by means of pupillary light reflexes, voluntary and involuntary eye
      movements, and visual evoked potentials. Systematically false responses contain
      useful information regarding the proof of misrepresentations. The reproducibility
      of visual field defects can be checked by testing at different distances from the
      screen. This article reports on handy methods requiring no large-scale equipment.

PMID- 9527584
TI  - [Single step implantable plate-haptic silicone lenses using the Passport system-
      initial experiences and results].
AB  - BACKGROUND: A new IOL implantation technique introduced in Germany since December
      1995 is presented--the one-piece-plate-haptic silicone lens implantable with the
      Passport system. METHOD: From January to September 1996 in 291 patients after 3.2
      mm clear cornea incision, capsulorhexis, phacoemulsification and implantation of
      an one-piece silicone posterior chamber lens with an implantation system was
      performed. The early post-operative results like visual outcome, astigmatism and
      complication rate are presented and compared to a group of 100 patients with
      implanted foldable three-piece silicone posterior chamber lenses. RESULTS AND
      DISCUSSION: The first post-operative day no statistically significant differences
      in visual outcome (mean: one-piece 0.71; three-piece 0.69), in absolute
      astigmatism (mean diopter 0.82 one-piece; 0.91 three-piece), in axial position
      and in complication rate were detectable. Differences of this new implantation
      technique compared to the conventional technique are discussed. CONCLUSION: The
      implantation of one-piece silicone lenses with the Passport system is a reliable
      and high quality alternative to conventional systems.

PMID- 9527585
TI  - [Ophthalmoscopic assessment of the size of the optic nerve papilla].
AB  - PURPOSE: To examine whether the optic disc size can be measured with common
      ophthalmoscopic lenses. PATIENTS AND METHODS: The horizontal and vertical disc
      diameters in 125 eyes of 65 patients were measured ophthalmoscopically using a
      commercial slit lamp with adjustable length of the beam and a Volk 60 diopters
      lens or a Volk Superfield lens. The refractive error of the subjects ranged
      between -7.25 D and +3.25 D (mean +/- S.D.: -0.34 +/- 1.77). Based on these
      measurements we calculated the optic disc area by applying a modified formula for
      an ellipse, where area = horizontal diameter x vertical diameter x pi/4.
      Additionally, we measured planimetrically the horizontal and vertical diameters
      of the optic disc on color stereo disc photographs after correcting the ocular
      and camera magnification according to Littmann's method. RESULTS: The values of
      the horizontal and vertical disc diameters evaluated on the photographs were by
      factors of 1.0 and 1.5 larger than those values measured with the Volk 60 D lens,
      and the Volk Superfield lens, respectively. Taking into account these constant
      linear correction factors, the optic disc diameters as measured by the Volk 60 D
      lens and the Volk Superfield lens varied by 0.11 +/- 0.09 mm (5.9 +/- 5.1%), and
      0.11 +/- 0.09 mm (5.9 +/- 4.9%), respectively, from the values measured on the
      photographs. The error for the ophthalmoscopic measurement of the disc diameters
      decreased slightly with increasing disc size. With highly myopic eyes excluded,
      it was independent of the refractive error. CONCLUSION: For clinical purposes,
      the optic disc and other structures of the posterior fundus can be determined by
      ophthalmoscopy using a slit lamp and commonly used ophthalmoscopical lenses.

PMID- 9527586
TI  - [Early diagnosis of pseudoexfoliation syndrome. A clinical electron microscopy
      correlation of the central, anterior lens capsule].
AB  - BACKGROUND: The intraocular manifestations of pseudoexfoliation (PEX) syndrome,
      with rising incidence with ageing, represent risk factors for patients undergoing
      intraocular surgery. Therefore we correlated our clinical assessment to
      transmission-electron microscopy. PATIENTS AND METHODS: 150 consecutive patients
      before extracapsular cataract surgery were examined for the occurrence of
      deposition of PEX material and other clinical alterations like PEX-phako,-irido,
      corneopathy and melanin-dispersion by slit-lamp biomicroscopy. These findings
      were compared with the electron-microscopic examination of the anterior lens
      capsules. RESULTS: In clinically manifest Mini- or classic PEX the clinical
      diagnosis was supported in all cases except one by electron microscopy. In EM
      classic PEX syndrome and precapsular layer was found in 37.3% of the cataract
      patients in this study group. The patients with the precapsular layer were
      significantly younger than the patients with classical PEX. The incidence of
      nuclear cataract, open angle glaucoma, corneal endotheliopathy and phacodonesis
      were more frequent in eyes where PEX was found on the anterior lens capsule in
      EM. In 14 of 92 (15.2%) patients the precapsular layer and PEX was not suspected
      with slit-lamp biomicroscopy. In 15 of 35 (42.8%) patients with suspected PEX the
      samples of EM of anterior lens capsules did not reveal PEX. CONCLUSIONS: PEX and
      its early forms seem to be found more frequently than expected in eyes with
      cataracts. Although biomicroscopy is a very valuable tool to detect early PEX
      syndrome, we have to improve the clinical criteria for the early diagnosis.

PMID- 9527587
TI  - [Possibilities and limits of extracranial vascular diagnosis with conventional
      echography].
AB  - BACKGROUND: For the extracranial and partial intracranial diagnosis of vessels
      Doppler ultrasonography has been the method of choice since a long time. If not
      the phenomenon of flow, but anatomical structures are of interest, or biopsy is
      planned, the conventional ultrasonography is often under-estimated. PATIENTS AND
      METHODS: A detection of the superficial temporal artery and its branches was
      performed in a clinical study of 50 patients by using a 10 Mhz ultrasonic system.
      The ultrasonic findings were correlated with clinical findings. RESULTS: The
      vessel course, the vessel was detectable diameter, plaques and stenosis and the
      perivascular tissue. CONCLUSIONS: The availability of conventional ultrasonic
      tools provides the possibility to achieve a fast first documentation of the
      extracranial vessels in a lot of inflammatory and arteriosclerotic diseases.

PMID- 9527588
TI  - [Mooren ulcer. 4 severe bilateral disease courses with systemic cyclosporin A
      therapy].
AB  - BACKGROUND: Mooren's ulcer is a rare autoimmunologic disease of the cornea. Many
      forms of medical and surgical treatments have been proposed in the past, but none
      of them was regularly successful. Severe progressive cases of Mooren's ulcer are
      therefore still a blinding disease. Only the use of systemic cyclosporin A (CSA)
      treatment appears for the first time to have a significant positive effect on the
      outcome. PATIENTS: One male (30 years old) and three female (52 y, 68 y, 84 y)
      patients with severe progressive bilateral Mooren's ulcer were treated with
      cyclosporin A systemically. RESULTS: On the male patient constant blood levels of
      CSA were not achievable and he became blind suffering basically from a severe
      proliferative diabetic retinopathy. The 52-year-old female patient got a relapse
      of Mooren's ulcer in the graft after penetrating keratoplasty a chaud. With
      increased blood levels of CSA the progression of the relapsing of Mooren's ulcer
      could be stopped. Also only with high-dose CSA further progression of the rapidly
      progressive colliquation of both corneas of a 68-year-old female could be
      stopped. A definitive improvement with some residual activity could be achieved
      in a 84-year-old female after only three months of follow-up. CONCLUSIONS: High
      dose systemic CSA treatment with plasma trough levels of 150-200 ng/ml is
      recommended as initial treatment of choice and should be started immediately. For
      what period of time after clinical healing this high-dose therapy must be
      contained without the risk of a relapse of Mooren's ulcer remains to be seen.

PMID- 9527589
TI  - [Block excision with tectonic corneoscleroplasty for cystic and/or diffuse
      epithelial invasion of the anterior eye segment. Report of 51 consecutive
      patients (1980-1996)].
AB  - PURPOSE: Many surgical and nonsurgical techniques for the treatment of cystic
      and/or diffuse sheet-like epithelial ingrowth of the anterior chamber led to
      recurrences or even enucleation of the eye. PATIENTS AND METHODS: There were 32
      (62.7%) men and 19 (37.3%) women ranging in age from 1 month to 80 years (median,
      55.5 years). Cystic epithelial ingrowth occurred in 45 patients, and diffuse
      sheet-like epithelial downgrowth in 6 patients. Block excision consisted of
      simultaneous en bloc removal of epithelial ingrowth together with adjacent iris,
      pars plicata of the ciliary body, and cornea and sclera in full-thickness. The
      resulting defect was covered with a tectonic corneoscleral graft. The median
      follow-up was 7.9 years. RESULTS: The main causes for epithelial ingrowth were
      trauma (41.2%) and complicated cataract extractions (27.5%). Eleven patients had
      undergone surgery of epithelial ingrowth before block excision, elsewhere.
      Epithelial ingrowth involved up to 5 clock hours of the circumference of the
      chamber angle (median, 3 clock hours). The median preoperative visual acuity was
      0.3 (range, hand motions -1.0). The median diameter of the block excision was 8.0
      mm (range, 5.5-12.0 mm). The main postoperative complications were vitreous
      hemorrhage (27.5%) and corneal endothelial decompensation (21.6%). The median
      postoperative visual acuity was 0.2. Visual acuity was > or = 0.3 in 43.1% of
      patients and < 0.1 in 35.3% of patients. Visual results were significantly better
      after simultaneous cataract extraction with intraocular lens implantation (n =
      5). Histopathologically, the invading epithelium mainly consisted of
      nonkeratinizing squamous epithelium with goblet cells (64.7%). There was a
      secondary proliferation of corneal endothelium on the cyst's surface in 82.4% of
      patients. There was no clinical evidence of recurrence of epithelial ingrowth,
      and no enucleation had to be performed during follow-up. CONCLUSION: Block
      excision with tectonic corneoscleral grafting is the treatment of choice for
      cystic and/or diffuse sheet-like epithelial ingrowth of the anterior chamber or
      anterior uvea, retrospectively.

PMID- 9527590
TI  - [Histological characterization and classification of surgically excised choroid
      neovascular membranes].
AB  - PURPOSE: This study was undertaken in order to histologically characterize
      surgically-excised choroidal neovascular membranes and to correlate theses
      histologic findings with the fundus and fluorescein angiographic appearance.
      MATERIAL AND METHODS: Surgically-excised subfoveal choroidal neovascular
      membranes submitted in the time period from November 1994 to July 1996 were
      included in this study. The membranes were processed and evaluated by light and
      transmission electron microscopy. Some membranes were oriented by the surgeon and
      marked on their inner surface with India ink and the configurations of these
      membranes were recorded and correlated with the fundus and fluorescein
      angiographic features. RESULTS: Sixty-two choroidal neovascular membranes were
      available for this study. In 74% age-related macular degeneration was the
      underlying disease. Retinal pigment epithelium and endothelial lined vascular
      channels were present in over 87.5% of cases. Basal laminar (linear) deposit was
      only present in membranes excised from patients with age-related macular
      degeneration. In six cases with Gass Type II choroidal neovascular membranes the
      histologic-clinical-fluorescein angiographic correlation showed well-defined
      (classic) neovascular membranes according to the criteria of the Macular
      Photocoagulation Study. Two membranes were not surrounded by retinal pigment
      epithelium and were classified as Type IIa membranes. Four membranes were
      surrounded by retinal pigment epithelium and classified as Type IIb membranes.
      CONCLUSIONS: Choroidal neovascular membranes represent a stereotypic, non
      specific wound repair response to a specific stimulus. Retinal pigment epithelium
      may proliferate around and attempt to wall off choroidal neovascular membranes.
      We propose a new classification of surgically-excised choroidal neovascular
      membranes as Types I, IIa, and IIb.

PMID- 9527591
TI  - [Video recording after visualization of conjunctival lymph vessels].
AB  - AIM: The aim of the investigation is a combination of a harmless and easy method
      of visualisation with a suitable way or recording of the dynamic processes of
      flow of dye in the lymphatic vessels of the conjunctiva in human eyes in vivo.
      METHOD: A visualisation method of injecting subconjunctivally 0.10 ml of a 2.5%
      solution of Patentblau V, was employed to study the initial lymphatic vessels
      (LV) of conjunctiva. The penetration of the dye in the LV was observed through an
      operating microscope and was filmed with the video camera attached. The anatomy
      of the initial LV of the conjunctiva, their size, the speed of lymph flow and the
      time necessary for the diffusion of the dye through the LV walls were recorded.
      PATIENTS AND RESULTS: The method was applied to 16 patients suffering from
      various ophthalmologic and general disorders. Well-shaped lymph vessels in the
      conjunctiva are located circularly around the limbus, at a distance of 3-5 mm.
      These LV often resemble rosaries consisting of separate segments (lymphangions).
      The lymph flow varies in speed. When the valves shut completely, the speed of the
      lymph flow in the respective lymphangion equals 0, but when the valves open, the
      lymph may gradually or rapidly stream into the next lymphangion. The LV vary
      greatly in size, which depends mainly on the quantity of liquid that has
      penetrated inside them. CONCLUSION: The time necessary for the dye to diffuse
      through the LV walls also varies greatly and depends on the type and dynamics of
      the disorder of the anterior eye segment, as well as on the general vascular
      disorders of individual patients and their effect on the permeability of the LV
      walls.

PMID- 9527593
TI  - [Bilateral adult periocular xanthogranuloma].
AB  - PATIENT: A 62-year-old woman was evaluated for a bilateral subconjunctival mass
      that had been present for 6 months. With magnetic resonance imaging the lesion
      could not be delineated form the lacrimal glands. A biopsy was performed and
      histologic examination exhibited a xanthogranulomatous lesion with multiple giant
      cells of the Touton type. The differential diagnosis of the adult xanthogranuloma
      is Erdheim-Chester disease, necrobiotic granuloma, xanthoma, Langerhans
      histiocytosis, and Rosai-Dorfman syndrome. CONCLUSION: Hyperlipemia should be
      excluded, in addition, in the presence of necrobiosis, paraproteinemia.

PMID- 9527592
TI  - [Massive reactive gliosis of the retina].
AB  - BACKGROUND: Massive retinal gliosis is a rare, extreme form of a reactive glial
      cell proliferation and can cause difficulties in the differential diagnosis of
      intraocular tumors. PATIENT AND METHODS: A 33-year-old patient presented with a
      painful neovascular glaucoma and a solid intraocular mass. The left globe was
      subsequently enucleated. The fundus could not be visualized due to lens opacities
      and an incomplete occlusive membrane. The findings of the magnetic resonance
      imaging were compatible with an intraocular malignant choroidal melanoma.
      RESULTS: Histologically the intraocular tumor proved to be a massive retinal
      gliosis replacing all retinal layers. Immunohistological reactions were positive
      for GFAP ("glial fibrillary acidic protein"). There were many dilated vessels
      within the glial mass. CONCLUSIONS: Massive proliferations of glial cells
      represent secondary changes which are usually found in blind eyes with various
      underlying diseases. They can be confused with other intraocular tumors,
      particularly if the fundus cannot be visualized. Ultrasound-reflectivity and
      magnet resonance imaging findings of massive retinal gliosis may resemble a
      malignant choroidal melanoma.

PMID- 9527594
TI  - Mismatch-stimulated destruction of intermediates as an explanation for map
      expansion in genetic recombination.

PMID- 9527595
TI  - Successful defibrillation on a beach by volunteer surf lifesavers.

PMID- 9527596
TI  - [Organ transplantations--an established form of therapy].

PMID- 9527597
TI  - [Dopamine and addictive diseases].

PMID- 9527598
TI  - [Treatment possibilities in bronchial asthma. Alternative methods, naturopathy
      methods, academic medicine. German Respiratory Tract Group e.V., German Allergy
      and Asthma Society e.V., Patient Group of Respiratory Tract Diseases e.V].

PMID- 9527599
TI  - [Thrombosis caused by estrogens. Genetic predisposition or induced by biochemical
      metabolic processes?].

PMID- 9527600
TI  - [Salmonellosis. Detection, control, prevention].

PMID- 9527601
TI  - [Shigella dysentery. Detection, control, prevention].

PMID- 9527602
TI  - [The year of "sartanes" and "triptanes"].

PMID- 9527603
TI  - [Vertigo].

PMID- 9527604
TI  - [HIV infection: antiretroviral therapy 1997. Consensus statement of the
      International AIDS Society-USA Panel].

PMID- 9527605
TI  - [Dietary salt and hypertension?].

PMID- 9527606
TI  - Organochlorine residues and breast cancer.

PMID- 9527607
TI  - Organochlorine residues and breast cancer.

PMID- 9527608
TI  - Organochlorine residues and breast cancer.

PMID- 9527609
TI  - Organochlorine residues and breast cancer.

PMID- 9527610
TI  - Organochlorine residues and breast cancer.

PMID- 9527611
TI  - Organochlorine residues and breast cancer.

PMID- 9527612
TI  - Complete remission of metastatic cervical cancer with the angiogenesis inhibitor
      TNP-470.

PMID- 9527613
TI  - Familial Mediterranean fever gene.

PMID- 9527614
TI  - Familial Mediterranean fever--amyloidosis and the Val726Ala mutation.

PMID- 9527615
TI  - Small-vessel vasculitis.

PMID- 9527616
TI  - Pernicious anemia.

PMID- 9527617
TI  - The significance of the Nuremberg Code.

PMID- 9527618
TI  - Cyclic changes in NMDA receptor activation in hippocampal CA1 neurons after
      ischemia.
AB  - We studied N-methyl-D-aspartate (NMDA) receptor-mediated synaptic potentials in
      CA1 pyramidal neurons using hippocampal slices of gerbils after transient
      forebrain ischemia. In the presence of 6-cyano-7-nitroquinoxaline-2,3-dione
      (CNQX) and bicuculline, stimulation of Schaffer collateral/commissural fibers
      induced field excitatory postsynaptic potentials (fEPSP) activated by NMDA
      receptors. We found that in many slices after ischemia, prolonged low-frequency
      stimulation (0.1-10 Hz) caused repeated depression and potentiation of the NMDA
      mediated fEPSP. Changes in fEPSP amplitude were dependent on stimulus frequency
      and the cycle frequency ranged from 0.08 to 2.5 cycles/min. These cyclic changes
      were blocked by application of BAPTA-AM, a membrane-permeable Ca2+ chelator, but
      were little affected by application of verapamil or by lowering the Ca2+ in
      bathing solution. Intracellular recordings from CA1 neurons revealed that low
      frequency stimulation caused periodic depolarizations of membrane potential
      accompanied by depression of the excitatory postsynaptic potentials. The cyclic
      changes of fEPSPs were blocked by inhibitors of protein kinase C (PKC) but were
      unaffected by inhibitors of Ca2+/calmodulin-dependent protein kinase II (CaMKII)
      or myosin light-chain kinase (MLCK). These results suggest that stimulus
      dependent NMDA-receptor activation, mediated by PKC, takes place in the
      postischemic CA1 neurons and that the cyclic change may reflect abnormal
      intracellular Ca2+ signaling processes leading to neuronal degeneration.

PMID- 9527620
TI  - Appearance of a fast inactivating voltage-dependent K+ currents in developing
      cerebellar granule cells in vitro.
AB  - To elucidate the molecular mechanisms that regulate the maturation of action
      potential, we began by examining voltage-dependent K+ currents, known to
      contribute to the maturation of action potential, of developing granule cells in
      mouse cerebellar microexplant cultures. The migration of developing granule cells
      in this culture is reported to mimic the in vivo process, but their specific
      identification is still incomplete. In this study, we identified and
      characterized granule cells in this culture. Immunocytochemical analysis found
      that granule cells migrated radially out from explants and subsequently formed
      small clusters and also that their morphology changed from a bipolar to a T shape
      during migration. Moreover, in the electrophysiological study, the GABA response
      of granule cells in this culture clarified that the electrophysiological
      properties of granule cells were normally maintained. We therefore have
      concluded, that this culture system is a powerful tool for investigating the
      differentiation of cerebellar granule cells. Based on these findings, we recorded
      voltage-dependent K+ currents of developing granule cells in this culture, while
      concurrently observing their morphology. Our results show that voltage-dependent
      K+ currents of developing granule cells change from delayed rectifier to A
      current in parallel with their morphological changes from bipolar to T-shaped
      cells.

PMID- 9527619
TI  - Lombard reflex during PAG-induced vocalization in decerebrate cats.
AB  - The Lombard reflex occurs when a speaker increases his vocal effort while
      speaking in the presence of ambient noise. The purpose of this study was to
      clarify whether the Lombard reflex can be evoked during controlled vocalization
      in an animal model. In decerebrate cats, repetitive electrical stimulation was
      applied to the midbrain periaqueductal gray (PAG) to evoke vocalization. Pure
      tone auditory stimulation was delivered through a loudspeaker. The activities of
      the laryngeal adductor muscle, diaphragm and external oblique abdominal muscle
      and the voice intensity were measured during PAG stimulation, in the presence and
      absence of the auditory stimulation. To clarify the effects of the auditory
      laryngeal reflex on the activity of laryngeal adductor motoneurons, the amplitude
      of the laryngeal reflex evoked by single shock stimulation of the superior
      laryngeal nerve was also measured during respiration, in the presence and absence
      of auditory stimulation. The sound made by the cats due to PAG-induced
      vocalization was augmented by exposure to auditory stimulation, and the
      activities of the laryngeal adductor muscle and external oblique abdominal muscle
      were also augmented. During respiration, auditory stimulation also increased the
      amplitude of the laryngeal reflex evoked in the laryngeal adductor muscle. These
      results demonstrate that the essential neuronal mechanisms for evoking the
      Lombard reflex exist within the brainstem.

PMID- 9527621
TI  - Neurochemical and metabolic consequences of elevated cerebrospinal fluid
      quinolinic acid concentrations in rat brain.
AB  - Quinolinic acid (QUIN) is an endogenous excitatory amino acid, which is elevated
      in brain tissues or cerebrospinal fluid (CSF) in several acute and chronic
      inflammatory central nervous system (CNS) diseases. The functional significance
      of this elevation is unknown but speculations of excitotoxicity have been raised.
      We have begun to address the pathologic consequences of elevated CSF QUIN by
      studying the effects of intracerebroventricular (i.cv) administration of QUIN on
      regional choline acetyltransferase (ChAT) activity, somatostatin content and
      glucose metabolism in the rat brain. QUIN (12 and 60 nmol) i.cv administration
      once a day for 7 days (total dose; 84 and 420 nmol, respectively) had minimal
      effect on somatostatin content and no effect on ChAT activity. In contrast,
      following continuous i.cv infusion of QUIN for 14 days using an osmotic minipump
      (480 nmol), ChAT activity dropped in the hippocampus and the striatum and
      somatostatin content was reduced in the frontal cortex, hippocampus, striatum and
      amygdala. Moreover, following the QUIN infusion, glucose utilization decreased in
      the basal nucleus of Meynert, frontal cortex, and portions of the basal ganglia
      and the limbic system. These results indicate that subchronic i.cv infusion of
      QUIN to rats results in selective regional neurochemical and metabolic changes
      distributed throughout the CNS. These results suggest target brain areas and
      transmitter systems which may be associated with neurologic syndromes
      characterized by elevated CSF QUIN levels.

PMID- 9527623
TI  - Effect of repeated cold stress on capsaicin-evoked release of glutamate from rat
      spinal dorsal horn slices.
AB  - We investigated the effect of repeated cold stress (RCS) on the capsaicin-evoked
      release of glutamate from the primary afferent fibers of the rat, and compared
      this with the effect of inoculation of complete Freund's adjuvant (adjuvant
      inoculation). The release of glutamate was measured using a fluorometric on-line
      continuous monitoring system in which the immobilized glutamate dehydrogenase
      column was connected to an in vitro superfusion system. In the presence of 0.3
      microM tetrodotoxin, the application of 1 microM capsaicin to spinal dorsal horn
      slices evoked glutamate release (18.6 +/- 1.2 pmol mg(-1) protein, n = 11). In
      rats subjected to RCS (RCS rats), the release of glutamate evoked by 1 microM
      capsaicin was markedly increased to 272% (n = 6, P < 0.05) of the value for the
      control group, although the basal release was not significantly altered (n = 6, P
      > 0.05). Adjuvant inoculation produced a significant increase in the basal and
      capsaicin (1 microM) evoked release of glutamate to 141 and 344% (n = 6, P <
      0.05) of the value for the control group, respectively. The present results
      suggest that the facilitated release of glutamate from capsaicin-sensitive
      primary afferent terminals in the spinal dorsal horn is, at least in part,
      involved in the hyperalgesia of RCS rats as well as the complete Freund's
      adjuvant-induced hyperalgesia.

PMID- 9527622
TI  - Nicotine increases cytosolic Ca2+ in vasopressin neurons.
AB  - Strong immunoreactivity for neuronal nicotinic acetylcholine receptor alpha4
      subunit was detected in neurons of the supraoptic nucleus (SON). At the
      ultrastructural level, immunoreactivity for alpha4 was detected in the post
      synaptic membranes as well as in the cytoplasmic matrices in the magnocellular
      neurons. Nicotine (1-10 microM) increased cytosolic Ca2+ concentrations ([Ca2+]i)
      in isolated arginine-vasopressin (AVP)-containing neurons in the rat SON.
      Nicotine (10 microM) was less potent in increasing [Ca2+]i in AVP-containing
      neurons than noradrenaline (1 microM), a known neurotransmitter in the SON. The
      nicotine-induced [Ca2+]i increase in AVP-containing neurons was markedly reduced
      when pre-treated with a protein kinase A (PKA) blocker, H89 (40 microM). These
      findings suggest that nicotine, a known neurotransmitter in the SON, activates
      AVP-containing neurons via nicotinic acetylcholine receptor which is linked to
      stimulation of cAMP-PKA-regulated Ca2+ signaling pathway.

PMID- 9527624
TI  - Activation of adenosine A1 and A2 receptors differentially affects acetylcholine
      release from electric organ synaptosomes by modulating calcium channels.
AB  - Adenosine inhibited the release of acetylcholine (ACh) evoked by high K+
      depolarization from synaptosomes isolated from the electric organ of the Japanese
      electric ray Narke japonica. The adenosine A1 receptor agonist N6
      cyclohexyladenosine was an effective inhibitor. Conversely, in the presence of an
      A1 receptor antagonist, 8-cyclopentyltheophylline, adenosine potentiated the
      release of ACh. The A2 receptor agonist N6-[2-(3,5-dimethoxyphenyl)-2-(2
      methylphenyl)ethyl] adenosine also facilitated the evoked ACh release. Thus,
      adenosine inhibits the evoked release of ACh via the A1 receptor while it
      facilitates the release via the A2 receptor. The EC50 for inhibition and
      facilitation by adenosine was about 1 and 41 microM, respectively. There are
      three known types of calcium channels (N-, P/Q- and L-type) in synaptosomes. The
      effects of Ca2+ channel type-specific blockers on the modulation of ACh release
      by adenosine A1 or A2 receptor activation revealed that inhibition by A1 receptor
      activation was caused via inhibition of N-type calcium channels and the
      facilitative effects by A2 receptor activation was mediated by potentiation of P
      type calcium channels.

PMID- 9527625
TI  - Platelet-derived growth factor prevents ischemia-induced neuronal injuries in
      vivo.
AB  - Platelet-derived growth factor (PDGF) has been considered to be a neuroprotective
      factor candidate on the basis of several in vitro studies. However, the in vivo
      effect of PDGF on ischemic neurons has not been determined. In the present study,
      the effect of PDGF-BB on the ischemia-induced disability of passive avoidance
      task and hippocampal CA1 neuron death in normothermic gerbils, whose the brain
      temperature was kept at 37.0 +/- 0.2 degrees C during 3-min occlusion of the
      common carotid arteries was investigated. When PDGF-BB was continuously infused
      for 7 days into the cerebral ventricles of gerbils with transient forebrain
      ischemia, response latency time in a passive avoidance task was significantly
      prolonged. Subsequent histological examinations showed that PDGF-BB effectively
      increased the number of viable pyramidal neurons in the hippocampal CA1 region as
      well as synapses within the strata moleculare, radiatum and oriens of the region
      in comparison with the numbers of neurons and synapses in vehicle-treated
      ischemic gerbils. In situ detection of DNA fragmentation (TUNEL staining)
      revealed that TUNEL-positive neurons in the hippocampal CA1 field of vehicle
      treated ischemic gerbils were much more numerous than those in the field of PDGF
      BB-treated ischemic animals after 7 days ischemia. These findings suggest that
      the present ischemic animal model exhibits a more delayed neuronal degeneration
      of the hippocampal CA1 field than the conventional 5-min ischemic model and that
      the 7-day infusion of PDGF-BB, starting 2 h before ischemic insult, not only
      prevents delayed neuronal death in the hippocampal CA1 field at 7 days after
      forebrain ischemia but also inhibits a slowly progressive neuronal degeneration
      occurring thereafter.

PMID- 9527626
TI  - Beta-estradiol protects hippocampal CA1 neurons against transient forebrain
      ischemia in gerbil.
AB  - Beta-estradiol has been considered to be a neurotrophic agent, but its in vivo
      effect on gerbils with transient forebrain ischemia has not yet been
      demonstrated. In the first set of the present experiments, we infused beta
      estradiol at a dose of 0.05 or 0.25 microg/day for 7 days into the lateral
      ventricles of normothermic gerbils starting 2 h before 3-min forebrain ischemia.
      Beta-estradiol infusion at a dose of 0.25 microg/day prevented significantly the
      ischemia-induced reduction of response latency time as revealed by a step-down
      passive avoidance task. Subsequent light and electron microscopic examinations
      showed that pyramidal neurons in the hippocampal CA1 region as well as synapses
      within the strata moleculare, radiatum and oriens of the region were
      significantly more numerous in gerbils infused with beta-estradiol than in those
      receiving saline infusion. Beta-estradiol at a dose of 1.25 microg/day was
      ineffective and occasionally increased the mortality of experimental animals.
      Since the total brain content of exogenous beta-estradiol at 12 h after forebrain
      ischemia was estimated to be less than 145 ng, the second set of experiments
      focused on the neurotrophic action of beta-estradiol at concentrations around 100
      ng/ml in vitro. Beta-estradiol at concentrations of 1-100 ng/ml facilitated the
      survival and process extension of cultured hippocampal neurons, but it did not
      exhibit any significant radical-scavenging effects at the concentration range. On
      the other hand, 100 microg/ml of beta-estradiol, even though failing to support
      hippocampal neurons in vitro, effectively scavenged free radicals in subsequent
      in vitro studies, as demonstrated elsewhere. These findings suggest that beta
      estradiol at a dose of 0.25 microg/day prevents ischemia-induced learning
      disability and neuronal loss at early stages after transient forebrain ischemia,
      possibly via a receptor-mediated pathway without attenuating free radical
      neurotoxicity.

PMID- 9527627
TI  - [The choice of transplantation in reconstructive surgery of the larynx after
      partial laryngectomy].
AB  - Hitherto applied methods of larynx reconstruction after laryngectomies of various
      extension or extended by the tongue base were discussed. Disadvantages of
      hitherto applied transplants were pointed out. The possibility of application of
      vascular pedicle transport of thyroid gland or submandibular gland for larynx
      reconstruction was presented.

PMID- 9527628
TI  - [The evaluation of respiratory function in children with chronic allergic
      rhinitis].
AB  - The aim of the paper is to assess respiratory functions in children with chronic
      allergic rhinitis. Multiple spirometric measurements were performed during oral
      and nasal ventilation and after nasal provocation with histamin and allergen. We
      find that spirometric measurements during nasal ventilation are very useful
      because they objectivize the degree of nasal patency disturbances. We have also
      noted the occurrence of bronchospastic reactions after nasal provocations.

PMID- 9527630
TI  - [Therapeutic issues in the case of one hearing ear].
AB  - The paper presents some important facts relating to the dangerous cases with one
      remaining functional ill ear. What should one do when a patient presents with a
      potentially dangerous chronic otitis media and the other ear is absent? The
      analysis of such dangerous cases with cholesteatoma, more especially those with a
      labyrinhine fistula and a cases with sudden deafness contralaterally shows that
      caution and responsibility has to be taken.

PMID- 9527629
TI  - [Acute fibromatosis from the standpoint of otolaryngology].
AB  - Aggressive fibromatosis in the otolaryngological region is a curious clinical
      entity, demanding accurate histopathologic interpretation. It is rare connective
      tissue tumor, which growth infiltratively with a destructive biological behaviour
      similar to malignant tumours and a high recurrence rate. Morphologically reactive
      fibromatosis and fibrosarcoma should be considered amongst others in differential
      diagnosis. CT and MR scans are useful in determining the extent of the tumors and
      help to distinguish the tumor from nerves, vessels and bone. Surgery is the
      treatment of choice. Our observations of the course of disease in the maxillary
      sinus, nasal cavity and nasopharynx confirmed the date in literature.

PMID- 9527631
TI  - [The latency and time of the growing reflex in the stapedius muscle].
AB  - Latency time and rise time of the stapedius muscle reflex were examined in 32
      healthy young people. No significant difference between woman and man were
      reflected. Obtained result were compared with the previous data of the various
      authors. Necessity of the own norm estimation of this parameters were emphasized.

PMID- 9527632
TI  - [Current criteria and methods of hearing aids fitting].
AB  - The contemporary criteria of hearing aids fitting were presented. The several
      hearing aids selection procedures such as POGO, Berger, NAL etc. were described
      in details. They are based generally on audiometric hearing threshold
      measurements. Some of the main differences have been also discussed.

PMID- 9527633
TI  - [A case of schwannoma in the parotid gland].
AB  - The authors described a very rare case of intraparotid Schwannoma in 39 year old
      female. The tumor originated from jugulare ramus at the facial nerve. The patient
      undergone surgical treatment.

PMID- 9527634
TI  - [A case of neurilemmoma of the larynx].
AB  - The rare case of neurilemmoma of the larynx was presented. The difficulties in
      histopathologic diagnosis of such tumors were emphasized. The tumor was removed
      by surgery from external approach.

PMID- 9527635
TI  - [A case of frontal sinus osteoma with unusual clinical course].
AB  - The case of frontal sinus osteoma causing exophtalmus and brain compression was
      presented. The osteoma was removed surgically. The information connected with
      histopathological and clinical features of the tumor were shown. The review of
      literature was presented.

PMID- 9527636
TI  - [A fulminant form of Wegener's granulomatosis].
AB  - The authors present the young man case who had undergone 6 months long antibiotic
      therapy first, than has been operated because of growing nose obstruction with
      bloody pus secretion. Diagnostic difficulties were responsible for diagnosis and
      undertaking treatment. Fulminant course of disease resulted in death of patient
      in the course of immunosupression therapy.

PMID- 9527637
TI  - [Usefulness of determining selected neoplasm markers: CEA, SCC and ferritin in
      patients with laryngeal tumors].

PMID- 9527638
TI  - Characterization of ecto-ATPase of Xenopus oocytes and the inhibitory actions of
      suramin on ATP breakdown.

PMID- 9527639
TI  - Symposium on RNA Biology II. RNA: Tool and Target. Research Triangle Park, North
      Carolina, USA. October 17-19, 1997. Proceedings.

PMID- 9527640
TI  - Endotoxin increases oxidative injury to proteins in guinea pig liver: protection
      by dietary vitamin C.
AB  - Current information suggests that oxidative damage plays a key role in septic
      shock induced by endotoxin. This raises the possibility that dietary antioxidant
      vitamins could protect against endotoxin damage. In this study, the effects of
      endotoxin administration on protein and lipid oxidative damage and endogenous
      antioxidants were studied in the liver of guinea pigs previously supplemented
      with marginal or optimum levels of dietary vitamin C, vitamin E or both. Vitamins
      C and E inhibited in vitro lipid peroxidation in endotoxin-treated animals.
      Endotoxin significantly increased oxidative damage to liver proteins in animals
      receiving low doses of both vitamins, a result described here for the first time.
      This increase was totally prevented in guinea pigs supplemented with vitamin C
      alone or in combination with vitamin E, a treatment which strongly increased
      liver ascorbate. Vitamin C caused small significant increases in superoxide
      dismutase and glutathione, increased uric acid, and synergically increased alpha
      tocopherol levels in vitamin E-supplemented animals treated with endotoxin. The
      results show that dietary vitamin C protects against endotoxin-induced oxidative
      damage to proteins in the guinea pig liver. This seems mainly due to a direct
      protective effect of the increased hepatic ascorbate levels present in vitamin C
      supplemented animals.

PMID- 9527641
TI  - Systemic and ocular absorption and antagonist activity of topically applied
      cyclopentolate in man.
AB  - Ocular and systemic absorption and antagonist activity of topical 1%
      cyclopentolate were studied in 11 elderly patients undergoing extracapsular
      cataract extraction, and in 8 healthy female volunteers. The patients received
      two 35 microl drops of cyclopentolate unilaterally and the healthy volunteers one
      30 microl drop bilaterally to the lower conjunctival cul-de-sac of the eye. The
      drug concentrations were measured with radioreceptor assay and receptor
      occupancies with radiooccupancy assay using isolated rat brain muscarinic
      cholinoceptors. In the patient group, cyclopentolate concentrations in aqueous
      humour were approximately 3000 times higher than those in plasma. Muscarinic
      cholinoceptors were occupied totally (more than 99.9%) by aqueous humour and 3
      18% by plasma taken at 55-125 min. after the drug application. In healthy
      volunteers peak plasma concentration of cyclopentolate, 2.06+/-0.86 (mean+/-S.D.)
      nM, occurred at 53 min., maximum receptor occupancy being 5.9+/-2.1%. The maximum
      pupillary dilatation occured at 30 min. after the drug application. At the same
      time the near point of vision was extended to more than 50 cm in all subjects.
      After topical application plasma receptor occupancy was not high enough to cause
      any significant changes in heart rate and in PQ time. None of the subjects
      experienced subjectively or objectively adverse effects to be attributed to
      cyclopentolate.

PMID- 9527642
TI  - Comparative studies on the induction of muscle contracture in mouse diaphragm and
      Ca2+ release from sarcoplasmic reticulum vesicles by organotin compounds.
AB  - Effects of organotins, including triethyltin and tributyltin, on skeletal muscle
      were studied with diaphragm and isolated sarcoplasmic reticulum membrane
      vesicles. Triethyltin induced muscle contracture in mouse diaphragm while
      tributyltin had comparatively less potency and efficacy in inducing the muscle
      contracture. The contracture induced by tributyltin was inhibited when the
      diaphragm was pretreated with low Ca2+ medium or caffeine while the contracture
      induced by triethyltin persisted in the Ca2+-free medium but was inhibited by
      pretreatment of caffeine. Pretreatment of dithiothreitol blocked the contracture
      induced by tributyltin but not that by triethyltin. Triethyltin dose-dependently
      induced Ca2+ release from sarcoplasmic reticulum vesicles and inhibited the Ca2+
      ATPase activity. These results suggested that triethyltin induced contracture in
      mouse diaphragm was mainly by induction of Ca2+ release and inhibition of Ca2+
      uptake of the internal Ca2+ storage site the sarcoplasmic reticulum, while the
      tributyltin induced contracture might be due to enhancement of extracellular Ca2+
      influx which further induce the release of internal Ca2+ through the Ca2+-induced
      Ca2+ release mechanism.

PMID- 9527643
TI  - A fish oil-derived concentrate enriched in eicosapentaenoic and docosahexaenoic
      acid as ethyl esters inhibits the formation and growth of aberrant crypt foci in
      rat colon.
AB  - It was examined whether the fish oil derived n-3 fatty acid concentrate K85
      (51.0% of eicosapentaenoic acid, 35.3% of docosahexaenoic acid and 7.7% of other
      n-3 fatty acids, all as ethyl esters) could inhibit the initial formation of
      aberrant crypt foci and the later growth of pre-existing aberrant crypt foci in
      the colon of male F344 rats treated with the carcinogens dimethylhydrazine or
      azoxymethane, the proximate metabolite of dimethylhydrazine. Given
      intragastrically 5 times a week, K85 caused a dose-dependent reduction of the
      initial (week 0-6) formation of aberrant crypt foci induced by azoxymethane (2 x
      15 mg/kg body weight/injection the first two weeks). The number of aberrant crypt
      foci was reduced by 36% (P < 0.001) with 3.0 g K85/kg body weight/dose, the
      largest dose tested. The reduction was most pronounced (46%, P = 0.009) among the
      fastest growing aberrant crypt foci (foci with 3 or more aberrant crypts). When
      given in a later phase of the carcinogenesis (week 17-23) a similar intragastric
      treatment with K85 caused a dose-dependent reduction of the growth of pre
      existing aberrant crypt foci induced by dimethylhydrazine (3 x 20 mg/kg body
      weight/injection the first week). The crypt multiplicity (aberrant crypt/focus)
      was reduced by 22% (P = 0.016) with 2.24 g K85/kg body weight/dose, the largest
      dose tested. This was sufficient to completely block the growth of the pre
      existing aberrant crypt foci in the treatment period. The arrest of crypt
      multiplication was further documented by the 63% reduction (P = 0.03) of the
      large aberrant crypt foci (foci with 9 or more aberrant crypts). The total number
      of aberrant crypt foci was not affected.

PMID- 9527644
TI  - Morphine-6-glucuronide-induced locomotor stimulation in mice: role of opioid
      receptors.
AB  - Morphine-6beta-glucuronide is a major metabolite of morphine with potent
      analgesic actions. To explore the importance of this opiate when administered as
      a drug by its own or in morphine action, we studied the locomotor activity
      response to morphine and morphine-6-glucuronide in drug-naive C57 BL/6JBom mice.
      The effects of administration of the two opiates on a battery of 7 different
      locomotor activities were studied and compared to saline controls. A dose of 20
      micromol/kg morphine-6-glucuronide resulted in more locomotion than the same dose
      of morphine, while at higher doses (up to 120 micromol/kg), similar increases for
      most locomotor behaviours were recorded for both drugs. Pretreatment with
      naltrindole indicated that the delta-receptors play an equivalent but minor role
      in mediating both morphine-6-glucuronide and morphine hyperlocomotion.
      Administration of high naltrexone doses (10 mg/kg) completely abolished the
      locomotor stimulation induced by both opiates. However, at intermediate
      naltrexone doses of 0.25 and 0.5 mg/kg, morphine-induced behaviours was
      completely inhibited while morphine-6-glucuronide induced behaviours demonstrated
      partial resistance to naltrexone inhibition. The mu1-specific receptor antagonist
      naloxonazine caused 75% reduction of morphine induced behaviours and only 50%
      inhibition of morphine-6-glucuronide induced behaviors. Taken together our
      observations indicated general similarity but also marked differences between
      morphine and morphine-6-glucuronide with respect to opiate receptors mediating
      the locomotor stimulatory effect.

PMID- 9527645
TI  - Tissue distribution of sex steroids: concentration of 17beta-oestradiol and
      cyproterone acetate in selected organs of female Wistar rats.
AB  - The tissue distribution of 17beta-oestradiol and cyproterone acetate was
      investigated after intravenous and intragastric administration to female Wistar
      rats by measuring the time course of the concentration of the sex steroids in
      plasma, liver, kidney, brain, and heart by radioimmunoassay. Test substances were
      administered intravenously in doses of 0.1 mg/kg each and intragastrically in
      doses of 10 mg/kg (17beta-oestradiol) and 0.1 mg/kg (cyproterone acetate)
      corresponding to the expected oral bioavailability. Tissue distribution was
      assessed within each mode of administration by AUCorgan/AUCplasma-quotients (Q
      values), and between both routes of administration by F-values representing (bio-
      and organ availability) and R-values, which express the organ load after
      intragastric compared to intravenous administration if the same amount of drug
      has been made bioavailable in the plasma after both routes (for explanation see
      next page). The absolute bioavailability of 17beta-oestradiol after intragastric
      administration of 10 mg/kg was ca. 8%. The oestradiol liver load after
      intragastric administration was about 20 times higher than after intravenous
      administration, whereas the drug load of other organs was independent of the
      administration route. Cyproterone acetate was completely bioavailable after
      intragastric administration in a dose of 0.1 mg/kg. Cyproterone acetate levels
      and AUC-values in all organs investigated were higher when compared to the plasma
      with highest levels in the liver. The organ distribution of cyproterone acetate
      including the drug liver load was independent of the route of administration.

PMID- 9527647
TI  - Anticonvulsant profile of 4-amino-(2-methyl-4-aminophenyl)benzamide in mice and
      rats.
AB  - An original ameltolide analogue 4-amino-(2-methyl-4-aminophenyl)benzamide, in
      which a second amino group has been introduced, was synthesized and evaluated for
      anticonvulsant activity. After intraperitoneal administration to mice, 4-amino-(2
      methyl-4-aminophenyl)benzamide was found active in the maximal electroshock
      seizure test and against the tonic seizures elicited either by bicuculline or 3
      mercaptopropionic acid. 4-amino-(2-methyl-4-aminophenyl)benzamide (4A-2M4A-PB)
      gave anti maximal electroshock seizures ED50 of 63 micromol/kg (15.4 mg/kg) and a
      TD50 of 676 micromol/kg (163 mg/kg), yielding a PI of 10.7; the potency is
      similar to that of the 4-amino-(2-methyl-3-aminophenyl)phthalimide (4A-2M3A-PP),
      superior to that of 4-amino-(2,6-dimethylphenyl)phthalimide (4A-2,6-DMPP), close
      to that of phenytoin and carbamazepine and inferior to that of ameltolide. 4A
      2M4A-PB with an ED50 of 41[28-60] micromol/kg (9.9 mg/kg) is as active after oral
      administration to rats as carbamazepine, more active than ameltolide, 4-A-2M3A-PP
      and phenytoin and slightly less active than the 4A-2,6-DMPP. The introduction of
      a second amino group on the substituted phenyl ring does not affect drastically
      the anticonvulsant potency after intraperitoneal administration to mice;
      moreover, it seems to enhance the activity after oral administration. 4A-2M4A-PB
      is a good candidate both for further pharmacokinetic studies and for the study of
      the precise mechanism of action.

PMID- 9527646
TI  - Nitric oxide donor NOR 3 inhibits ketogenesis from oleate in isolated rat
      hepatocytes by a cyclic GMP-independent mechanism.
AB  - Studies were conducted to clarify the effects of nitric oxide donors NOR 3 ((+/-)
      (E)-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexeneamide, FK409), SIN-1 (3
      morpholinosydnonimine) and SNAP (S-nitroso-N-acetylpenicillamine) on the
      accumulation of cGMP and cAMP and Ca2+ mobilization as well as ketogenesis from
      oleate in isolated rat hepatocytes. NOR 3 caused inhibition of ketogenesis from
      oleate along with stimulation of cGMP accumulation in rat hepatocytes, whereas
      SIN-1 and SNAP exerted no effect on ketogenesis despite their marked stimulation
      of cGMP accumulation. Although the nitric oxide trapping agent, carboxy-PTIO (2
      phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide), antagonized the
      stimulation by NOR 3 of cGMP accumulation, it failed to modulate the anti
      ketogenic action of NOR 3. Furthermore, neither 8-bromoguanosine-3',5'-cyclic
      monophosphate nor N2,2'-O-dibutyrylguanosine-3',5'-cyclic monophosphate mimicked
      the anti-ketogenic action of NOR 3. It is concluded in the present study that NOR
      3-induced inhibition of ketogenesis in rat hepatocytes is not mediated by cGMP.
      The present study revealed that the remaining structure of NOR 3 from which
      nitric oxide had been spontaneously released had no anti-ketogenic action. We
      first and clearly demonstrated that nitrite production was dramatically enhanced
      when NOR 3 was incubated in the presence of rat hepatocytes. The mechanism
      whereby NOR 3 inhibits ketogenesis in rat hepatocytes will be discussed.

PMID- 9527648
TI  - Lower urinary recovery of oral morphine in Saudi Arabian cancer patients compared
      to Swedish cancer patients.

PMID- 9527649
TI  - [Aggression in elderly persons with psychiatric disorders].
AB  - In recent years aggression among elderly patients with psychiatric disorders has
      become an area of scientific research. A review of 19 reports, mostly from the
      USA, shows that a great part of these people demonstrate aggression of varied
      intensity. It is often a very serious problem for family members and a reason for
      psychiatric admissions. The aggression-index in this population varies depending
      on the place of living from 14% in the community, 12%-48% in adult homes to more
      than 60% in psychiatric hospitals. Nearly half of demented patients show
      aggressive behaviour in different situations, often of extreme intensity. Some
      reports suggest aggression to be more common among men, but perhaps only in
      association with dementia.

PMID- 9527650
TI  - [The prevalence of Alzheimer's type dementia and vascular dementia in the
      district of Swiebodzin].
AB  - In the study the prevalence of Alzheimer's type dementia and vascular dementia in
      the town of Swiebodzin and its surroundings was assessed. Also, the frequency of
      risk factors of vascular diseases for both types of dementia was evaluated. The
      study group comprised 7417 persons (45 years old and above). This population was
      divided into two groups. The younger subgroup (45-64 y) and the older one (65 y
      and above). The results obtained for indices of prevalence of both main types of
      dementia are comparable with the results that can be found in literature. The
      prevalence of Alzheimer's type dementia, in this study, is greater in women,
      while in men higher indices are referred to vascular dementia. The risk factors
      of cerebrovascular diseases are more frequent in the group of men. It could
      explain higher risk of vascular dementia in this group.

PMID- 9527651
TI  - [A case of total pseudoamnesia].
AB  - In our article we present a case of a 44-year old man, who was admitted to
      Psychiatry Ward with suspicion of total amnesy after trauma of head. In time of
      hospitalisation patient was showing symptoms of total loss of memory, loss of
      identity without losing general knowledge. During hospitalisation it appeared
      that due to the same problem (trauma of head) the patients was hospitalized twice
      in time of one month in Surgical Word with diagnosis of subarachnoid haemorrhage,
      which was not found in the second hospitalization. The patient spontaneously, in
      time of a few days, recalled all dates. On the basis of clinical picture and
      laboratory findings we diagnosed this case as: "Simulation of mental disorders.
      Status after trauma of head". This case is a very good example of using medical
      care for one's own purpose not connected with treatment.

PMID- 9527652
TI  - [Improvement criteria after neuroleptic treatment and clinical and
      neuroradiological factors in schizophrenic psychoses. Preliminary studies].
AB  - In 40 schizophrenic patients, various criteria of clinical improvement after
      neuroleptic treatment were compared in order to establish correlations between
      improvement after treatment and some clinical and MRI parameters. Three ways of
      evaluation of clinical improvement (CGI scale, PANSS index, percentage of
      improvement) correlated strongly with one another. Only the distribution of
      numbers of patients with different clinical improvement evaluated by the use of
      PANSS index was not statistically significant. Clinical improvement, evaluated
      with all three methods, significantly correlated with basal PANSS score as well
      as with the severity of positive symptoms and affective blunting, but not with
      the severity of schizophrenia negative symptoms. Only clinical improvement with
      the use of CGI demonstrated significantly better improvement in patients who had
      good previous response to neuroleptics. This particular method of clinical
      improvement evaluation, in contrast to other two methods, failed to reveal better
      response to neuroleptics among patients with no cortical atrophy found in MRI.
      Among patients with different improvement after treatment, evaluated with the use
      of all three methods, selected MRI parameters did not show significant
      differences with the exception of CGI improvement which correlated positively
      with the intensity of signal in T2-weighted image of gray matter in left medial
      frontal gyrus.

PMID- 9527653
TI  - [Selected parameters of magnetic resonance imaging of the brain, clinical picture
      and recovery after treatment in schizophrenia. Preliminary report].
AB  - In forty schizophrenic (or schizophreniform disorder) patients diagnosed
      according to DSM-IV, the magnetic resonance imaging was performed. The T2
      relaxation time was measured in selected brain regions from the dorsolateral
      prefrontal cortex as well as in amygdala. These results were compared with
      clinical parameters regarding severity of psychopathology and improvement after
      neuroleptic treatment. The mean T2 values of grey matter of right inferior
      frontal gyrus were significantly higher in patients with schizophreniform
      disorders (those patients were clinically diagnosed as suffering from cycloid
      psychoses) than in other types of schizophrenia. The T2 values of this region
      correlated inversely with the severity of negative symptoms before treatment. The
      T2 values of gray matter of left inferior frontal gyrus correlated positively
      with the severity of schizophrenic symptoms before treatment. Mean T2 values of
      left amygdala were significantly higher in patients showing less favorable
      improvement after neuroleptic treatment in comparison to those who improved
      better. No correlation was found between the presence of brain atrophy and T2
      values in brain regions studied. The results allow to suggest that the
      measurement of T2 relaxation time might reveal interesting relations between
      clinical picture and neuroradiologic findings in schizophrenia, however clinical
      significance of such parameters still requires further elaboration.

PMID- 9527654
TI  - [Electroconvulsive therapy in schizophrenia].
AB  - The author presents the actual state of knowledge about the mechanism of action
      of ECT with schizophrenia. An analysis of literature indicates that controversy
      about the role of ECT in the treatment of schizophrenia doesn't stop.

PMID- 9527655
TI  - [The diagnostic and therapeutic process in patients with a first episode of
      psychotic disorder at the inpatients department].
AB  - The paper presents the tradition of work on our inpatient ward, the specific
      character of diagnosis and treatment and their goals in relation to the first
      psychotic episode. Finally, some controversial issues concerning this subject are
      discussed.

PMID- 9527656
TI  - [Therapeutic effect of zuclopenthixol acetate on positive and negative symptoms
      in schizophrenia].
AB  - Fifty schizophrenic in-patients (DSM-IV) were treated in an open study with
      zuclopenthixol acetate. Mental status, improvement and side-effects were measured
      before administration of the drug as well as after the 1st, 2nd and 3rd
      injection. Positive and negative symptoms were evaluated with the use of PANSS.
      60% of patients received three injections. Usually the intervals between
      injections lasted 48 hours. The improvement after the 3rd injection of
      zuclopenthixol acetate was found in 80% of patients. All positive symptoms
      improved after the treatment (p < 0.001), among them excitement (54% reduction
      vs. baseline), hostility (49%) suspiciousness/persecution (45%). The study
      revealed that parallel to the decrease of positive symptoms, the severity of
      negative symptoms also decreased, in particular: difficulty in abstract thinking
      (28%) and stereotyped thinking (27%) (p < 0.001). Passive/apathetic social
      withdrawal and lack of spontaneity as well as flow of conversation only slightly
      improved (p < 0.05). 50% of patients experienced side-effects--usually
      extrapyramidal reactions.

PMID- 9527657
TI  - [The evaluation of reliability and validity of a preliminary version of the
      Clinical Assessment of Schizophrenic Syndrome (CASS)].
AB  - Basic indices of reliability and validity of a preliminary version of the new
      tool for "Clinical Assessment of Schizophrenic Syndrome" (CASS) was evaluated.
      Six experienced psychiatrists working in two teams examined the mental state of
      49 patients with clinical diagnosis of schizophrenia, in the majority of them
      confirmed by the criteria of DSM-IV and ICD-10 (one of the teams examined 25
      patients, the other-24). Each diagnostician rated the patients' mental state
      independently, by means of three-level rating permitted by the CASS-CASS-G
      (global), CASS-D (dimensions), and CASS-S (symptoms)--as well as by means of BPRS
      and PANSS scale included in the study as international standard scales for
      validity testing. Statistical analysis of the results confirmed that the scales
      under study allow to obtain results which could be characterized, with few minor
      exceptions, by high concordance coefficients (Kendall's W) high internal
      consistence coefficients (Cronbach's alpha) and high correlations (as measured
      both by Pearson's and Kendall's rank correlation coefficients taub) with
      internationally appreciated standard scales. It suggests reliability and validity
      of the CASS to the degree which could be considered as encouraging to continue
      the study on this instrument.

PMID- 9527658
TI  - [The evaluation of well-being of schizophrenic or depressed patients with
      Bradley's questionnaire: a pilot study].
AB  - Well-being of 65 in-patients with the diagnosis of schizophrenia or major
      depression was evaluated with the use of Bradley's well-being questionnaire. The
      severity of psychopathology as well as clinical improvement after pharmacotherapy
      were evaluated by doctors using CGI scale. Patients with the diagnosis of
      depression estimated their well-being lower in comparison to schizophrenics. The
      groups did not differ in the subscales of depression and energy. Female patients
      revealed more anxiety than male ones, regardless diagnosis. Physicians'
      evaluation of disease severity did not correlate with patients' well-being
      judgement using Bradley's questionnaire. After pharmacotherapy correlation
      between clinical improvement and several questions from Bradley's questionnaire
      was found.

PMID- 9527659
TI  - [Insight and psychotic illness].
AB  - This paper reviews the literature concerning the meaning of insight in clinical
      psychiatry. A number of studies indicate that insight is a complex and
      multidimensional phenomenon, consisting of at least several partly independent
      components (awareness of psychotic illness, the ability to recognize psychotic
      symptoms as pathological, the acceptance of treatment). It is suggested that good
      insight plays an important role in the course and treatment of psychotic
      disorders, and of schizophrenia in particular.

PMID- 9527660
TI  - [Mental disturbances in persons persecuted for political reasons in Poland in the
      years 1944-1955].
AB  - The paper presents the results of studies on the present state of mental health
      in persons persecuted for political reasons in Poland in the years 1944-1955.
      Symptoms of mental disturbances were detected in nearly all examined group. PTSD
      criteria were applied in the diagnosis.

PMID- 9527661
TI  - [Psychopathology of violent behavior in mental disorders].
AB  - The frequency of violent behaviour in mental hospitals has been increasing in
      recent years. A number of factors may be responsible. Violent and dangerous
      patients are sent to hospitals, quite often against their will. This may lead to
      conflicts and assaults against the staff members. There are many factors, both in
      present situation and in biography, conductive to violent behaviour: unfavourable
      experiences in childhood (neglect, cruelty, sexual exploitation), psychopathic
      structure of premorbid personality, frustrations, and eventually deformations of
      world perception caused by psychotic symptoms. Various mental disorders may lead
      to the violent behaviour, but it is most frequently observed in exacerbation of
      paranoid schizophrenia, in young males, particularly in cases with systemized
      delusions, emotional turmoil and anger. Introduction of a person (nurse,
      physician, family member, other patient) into psychotic world may also lead to
      the attack. In particular cases it is difficult to foresee violent behaviour, but
      some indicators are known. There are very few investigations on the role of the
      staff in violent behaviour of patients. The danger may be brought by criticism,
      refusal and rejection, compulsory drug administration, undue limitations of the
      patient's liberty, or the opposite--no reaction to violations of institutional
      regulations. Psychopathology of the staff may also encourage the violent
      behaviour: inability to solve the transference and countertransference, reaction
      formation and denial are the most important. Fear exaggerates the feeling of
      danger and induces the staff members to avoid the patient, diminishing the
      possibility of influence and control of the patient's disturbed behaviour.
      Recurrent violent behaviour may be connected with brain pathology, so the modern
      diagnostic procedures may be indicated in such cases.

PMID- 9527662
TI  - [Treatment by judicial obligation of alcohol dependent persons].
AB  - Treatment without consent of alcohol dependent persons has persisted for years in
      Poland. Only judicature determines obligation to treatment, which can be realized
      in ambulatory treatment or psychiatric ward. There are positive and negative
      aspects of such treatment. This article shows most of them, proposing a
      discussion of this problem again.

PMID- 9527663
TI  - [The comparison of concentration of endogenous ethanol blood serum in alcoholics
      and in non-alcoholics at different stages of abstinence].
AB  - In this report the concentration of endogenous ethanol in blood serum in
      alcoholics at different stages of abstinence and in non-alcoholics was studied.
      36 people--26 alcoholics and 10 non-alcoholics were examined and gas
      chromatography was used. It was revealed that the longer the period of abstinence
      in alcoholics, the lower the concentration of endogenous ethanol in blood serum.
      Moreover, the alcoholics showed a higher concentration of endogenous ethanol in
      blood serum as compared to non-alcoholics.

PMID- 9527664
TI  - [Carbamazepine in the treatment of alcohol withdrawal].
AB  - The authors present a review of literature on the initial rationale and efficacy
      in clinical trials of carbamazepine (CBZ) in the treatment of alcohol withdrawal,
      and the pharmacokinetics of carbamazepine in alcoholics as well.
      Neurophysiological and clinical studies support the kindling hypothesis in the
      pathophysiology of alcohol withdrawal. The exact physiological action mechanism
      of CBZ has not been entirely examined. However, the "antikindling effects" are of
      particular importance in epilepsy and other neurological and psychiatric
      conditions. Numerous controlled studies were able to demonstrate the
      effectiveness of carbamazepine in the treatment of alcohol withdrawal symptoms
      and have compared its properties to other drugs such as clomethiazole and
      benzodiazepines. Carbamazepine could be a useful alternative to conventional
      therapeutic approaches, especially in the treatment of mild and moderate alcohol
      withdrawal symptoms, and alcohol withdrawal with generalized tonic-clonic
      seizures.

PMID- 9527665
TI  - [HIV follow-up. New data on pathophysiology and treatment of psychiatric
      disturbances in the course of AIDS].
AB  - In the article summarized here, the authors present the most important
      achievements in the research on pathogenesis and treatment of AIDS, with
      particular consideration of psychiatric disturbances occurring in the course of
      infection by AIDS. Since the 1 st of January 1993, a new definition of AIDS has
      been obligatory. This definition is based on immunological criteria (HIV
      seropositivity and number of limphocytes CD4 < 200/microliter). There is a
      considerable progress in the scope of laboratory diagnostics of the infection by
      HIV (a method of polimerase chain reaction has been introduced) and in the
      laboratory and clinical appraisal of the development of AIDS. An astonishing
      capability of HIV to mutation has been proved. Asymptomatic HIV carriers show
      about 10(6) genetically different variants of HIV, and subjects showing symptoms
      of AIDS may prove over 10(8) HIV variants. This extreme dynamics of HIV causes
      that even the subjects who are not pharmacologically treated (but who are HIV
      seropositive) indicate the formation of mutants resistant to medicines applied in
      the treatment of AIDS. The only one and relatively efficient means of treatment
      of AIDS is combined therapy applied from the first weeks of the infection by HIV.
      Professor Luc Montanier, a co-discoverer of HIV virus suggests that the most
      efficient therapy is that by a medicine known as 3TC, in combination with DDI or
      DDC and with one of the drugs named anti-proteases. This method of treatment
      inhibits the activity of virus protease--one of 3 enzymes indispensable for
      replication of HIV. Recently (at the turn of the years 1995/1996) three medicines
      from the anti-protease group: saquinavir, ritonavir and indinavir have been
      admitted to be used for treatment of AIDS by the American agency for the control
      of drugs and foods. FDA, in the exceptionally short time. In the article there is
      also a description of a concept represented by R. Price, concerning the origin of
      psychiatric disturbances in the course of AIDS, as well as some results of recent
      clinical studies on psychiatric disturbances in the course of AIDS.

PMID- 9527666
TI  - [Psychiatric disorders and sensory deprivation in AIDS. Case report].
AB  - In AIDS there are several opportunistic infections that may occur. Some of them
      can lead to blindness (for example toxoplasmosis, CMV). It is known that
      psychiatric disorders can also occur in AIDS. Both situations can take place at
      the same time. In that case we face the diagnostic problem: Are psychiatric
      disorders a result of the sensoric deprivation connected with sudden blindness or
      organic changes in the brain caused by HIV? In our article we described the case
      of a 37 years old woman who had that kind of symptoms.

PMID- 9527667
TI  - [Mental disorders in the course of scleroderma: case reports].
AB  - In our paper current knowledge about mental disorders in the course of
      autoimmunologic diseases is presented. Two such cases (catatonic syndrome and
      major depressive episode) are described.

PMID- 9527668
TI  - [Mental disorders in patients after tick-borne encephalitis (TBE)].
AB  - There were 58 patients (aged 17 to 72) analyzed in our study: 34 women and 24 men
      one year after TBE. Psychic state was estimated with the use of psycho-pathologic
      scales CPRS, Hamilton Depression Rating Scale and Hamilton Anxiety Rating Scale,
      Mini Mental State and our own questionnaire. It was assumed that 22 patients
      required psychiatric treatment because of dementia, personality change,
      depressive disorder and anxiety disorder. It seems that so many syndromes stated
      in this group of patients were caused by TBE reaction increase of intellectual
      mnestic functions as well as social and professional status.

PMID- 9527669
TI  - [Diagnostic difficulties in encephalitis: two case reports].
AB  - The differential diagnosis of psychiatric symptoms in encephalitis, especially in
      the early phase of the disease may be very difficult. It is particularly hard to
      distinguish it from the classic psychosis. The diagnostic problems have been
      presented on the basis of analysis of two case reports of the acute encephalitis
      in young persons. The presence of fever and pathological changes in the CSF were
      the most important indicators that helped to establish the diagnosis of
      encephalitis during the phase of acute psychopathological disorders.

PMID- 9527670
TI  - [Assessment and self-assessment of patients' attitudes toward their psychotic
      disorders].
AB  - The aim of the study was the evaluation of concordance between rating and self
      rating of attitudes toward psychotic disorders in one hundred patients (72 of
      them with diagnosis of schizophrenia). At discharge from the hospital patients
      were examined by two scales: Experience of Illness Scale (for rating) and My
      Experience of Illness Scale (for self-rating). Moderate concordance of results of
      rating and self-rating of the overall patients' attitude was noted. The higher
      concordance was found on dimension of evaluation of the illness experience, lower
      on dimension of reflectiveness to disease experience, and the lowest one on
      dimension of identification of the disease with self. Two different scales,
      simultaneously used, seem very beneficial because they reflected attitudes from
      two different perspectives, creating more complete a picture.

PMID- 9527671
TI  - [A sense of coherence and mental disorders].
AB  - Sense of coherence, a health-promoting life orientation, i.e. perceiving the
      world as comprehensible, manageable and meaningful, was compared in three groups:
      of healthy controls (37 males and 45 females), neurotic patients (31 males and 54
      females), and hospitalized patients with depressive syndrome defined according to
      DSM-IV criteria (13 females). Two self-report questionnaires were used in the
      study: Antonovsky's SOC-29 scale measuring the sense of coherence, and SCL-90-R
      by Derogatis, measuring psychopathological symptoms intensity. As hypothesized,
      psychopathology level in the groups under study was significantly differentiated,
      being most marked in patients with depression. Sense of coherence and all its
      constituents turned out to be significantly lower in both clinical groups as
      compared to controls; the lowest SOC level was noted in depressive patients.
      Moreover, in the latter group, in contradistinction to the other two, significant
      correlations between sense of coherence (SOC) and general self-rated health
      (positive correlations), and between SOC and symptoms intensity (negative
      correlations) have disappeared. Due to the small size of the depressive group it
      was possible only to suggest a hypothesis explaining the findings, namely, that
      the SOC protective function disappears in persons situated far away from the
      "health" pole of the health-disease continuum.

PMID- 9527672
TI  - [The comparison of self-concept and self-acceptance in patients with paranoid
      schizophrenia and neurotic disorder].
AB  - Self-acceptance as a correlation between real and ideal self-concept
      distinguishes neurotic patients from paranoid schizophrenic patients. This fact
      may support the hypothesis that these groups of patients are characteristic of
      different personality traits.

PMID- 9527673
TI  - [The determination of social skills in schizophrenia].
AB  - The author describes a review of research concerning connection between the
      social skills in schizophrenia and each of the above factors. The problem of the
      influence of various factors upon the social skills in schizophrenia seems to be
      very important as far as therapeutic possibilities are concerned. Social skills
      are a "tool", used in all sorts of contact with other people. They are used both
      to achieve specific goals, and to satisfy various emotional and social needs.
      Schizophrenic patients have significantly worse level of social skills than non
      schizophrenic patients and healthy people. Deficits in social skills are present
      in all their aspects: in the topographical features, in the problem solving
      skills, etc. According to the model of social skills developed in The Clinical
      Research Center for Schizophrenia and Psychiatric Rehabilitation those skills
      consist of social schemata, interpersonal problem solving skills, social
      competence and self-efficacy. Social skills are determined by the cognitive
      processes, family environment and factors specific to schizophrenia, like
      premorbid functioning and psychopathological symptoms.

PMID- 9527674
TI  - [The features of family environment and social skills in schizophrenia].
AB  - The influence of environmental factors upon the social skills in schizophrenia is
      beyond doubt. The family environment of schizophrenic patients has been
      extensively described. Some research revealed those features of emotional context
      of the family, which influence the exacerbation of schizophrenia. Those features
      are called the Expressed Emotion Index (EE). The Expressed Emotion Index has
      great prognostic value and it seems interesting to examine the influence of the
      family environment as described by EE, upon the social skills. This paper
      contains both a characterization of the family environment described by various
      aspects of EE and an analysis of its influence on the social skills. Possible
      connections of EE with premorbid functioning of schizophrenic patients, and with
      psychopathological symptoms, as well as cognitive processes are also described.
      In the analysis of interrelation of EE and the social skills it is very important
      to consider both qualitative and quantitative aspects of Expressed Emotion Index.
      Various aspects of the family environment seem to be connected with specific
      cognitive dysfunctions and various psychopathological symptoms. In a similar way,
      various social skills seem to be determined by different internal and external
      factors.

PMID- 9527675
TI  - [Teaching schizophrenic patients self-care skills].
AB  - The level of knowledge and skills on self-care abilities has been examined among
      the group of 30 long-term patients suffering from schizophrenia. The research has
      been made four times during the period of 18 months after the training session
      had been completed. The final results show that three months duration of the
      training session exerts influence on the progress in learning and change of the
      view point. However, little change is observed as regards the daily functioning
      of patients.

PMID- 9527676
TI  - [The preliminary evaluation of quality of life in patients with chronic
      schizophrenia].
AB  - The aim of our work was to check out the usefulness of the questionnaire "Quality
      of Life". Thirty patients from day hospitals in Warsaw took part in the research.
      3/4 of the patients had indifferent attitude towards their clothes, environment,
      health and their lives generally. Everyday functioning is of some difficulty for
      the patients, and their families help them in everyday duties. Most of the
      patients can rely on their families in solving their problems. The higher was the
      patients' subjective level of functioning, the better was their quality of life.
      Estimation of everyday functioning made by patients themselves depends on the
      intensity of psychopathological symptoms. There is not such dependence concerning
      the patients' quality of life. Convergence between our data and data collected
      from the literature suggests usefulness of the questionnaire in the research on
      the quality of life of patients with mental illness.

PMID- 9527677
TI  - [Evaluation of health-related quality of life in hospitalized schizophrenics].
AB  - Health related quality of life was evaluated in 40 schizophrenics from day
      hospital at admission, during the treatment and after 8 weeks. In contrast to the
      psychopathology which significantly decreased after 4 weeks already, the
      improvement of quality of life was found to be significant only at the discharge
      from day hospital. The quality of life did not correlate with the severity of
      schizophrenic symptoms. The older and more frequently hospitalized patients were,
      the less favorably they evaluated the quality of life. Patients professionally
      disabled were also less pleased with their quality of life. All quality of life
      domains improved after treatment with the exception of physical functioning and
      reported health transition. Physical functioning, role-physical, general health
      and mental health correlated inversely with severity of schizophrenia after
      treatment. There was no correlation between clinical improvement after treatment
      and quality of life domains. The higher was the patients' educational level the
      better they evaluated their vitality, social functioning and reported health
      transition.

PMID- 9527678
TI  - [Evaluation of quality of life in patients with cancer].
AB  - Subjective evaluation of health related quality of life was studied in 53 cancer
      patients. The Polish version of quality of life questionnaire SF-36 was
      distributed among the patients before radiotherapy and repeated after one year.
      Significantly higher quality of life was found in the control measurement after
      one year in comparison to the evaluation before radiotherapy started. The quality
      of life estimated by the patients was not correlated with physician's evaluation
      of patients made with the use of the Zubrod scale. Patients in more advanced
      disability due to the cancer (Zubrod scale) evaluated their social activity
      better than did subjects less severely disabled and bed-bound. Patients' sex as
      well as the localization of the cancer did not influence their opinion regarding
      their quality of life. The severity of pain and discomfort the patients
      experienced before radiotherapy correlated with the evaluation of quality of
      life. The severity of pain and discomfort the patients experienced before
      radiotherapy correlated with the evaluation of quality of life. After one year
      the intensity of pain and discomfort correlated only with the patients' general
      health evaluation and with physical fitness but not with their social and daily
      activity.

PMID- 9527679
TI  - [Associative meaning of emotionally neutral words in a group of healthy and
      schizophrenic patients: a comparative study].
AB  - Distributions of associational responses--to four emotionally neutral stimulus
      words--obtained from schizophrenic people and sane ones were compared.
      Significant differences in some content categories were discovered.

PMID- 9527680
TI  - [Paradoxical reaction in a 18-year-old defendant with a diagnosis of immature
      personality with schizoid features: a case report].
AB  - We introduce a case of an 18 years old man suspected of murder attempt of his
      colleague. We made a diagnosis of immature personality with schizoid features; we
      also want to remind Edward Brzezicki's thoughts on paragnomen.

PMID- 9527681
TI  - [Designing a mental health system for children and adolescents].
AB  - Mental Health Act indicates childhood and adolescence as the periods of life
      requiring a special prophylactic, therapeutic and rehabilitative care. Planning
      future organization of mental health care for children and adolescents can be
      based on patterns developed in countries of longer tradition, as well as on
      suggestions of international bodies interested in improving health care.
      Desirable status, however, will remain at the project stage if the reality is not
      taken into account. Assessment of the particular community can be done with
      epidemiological studies which require highly trained professionals and are
      costly. Thus, epidemiological data can be used rather for modification of well
      developed care systems. Early start of training in mental health problems of
      children, adolescents and their families in undergraduate training of physicians
      seems to be very important, taking into account that development of specialized
      services requires support and cooperation of other doctors, e.g. general
      practitioners, and forms a background for postgraduate training in child and
      adolescent psychiatry. Professional, or rather multiprofessional associations of
      child and adolescent mental health care givers aiming at improvement of care
      system have a very important role in lobbying for changes essential for
      realization of any design.

PMID- 9527682
TI  - [Early detection of autism in children. Review of literature].
AB  - The difficulties with early detection of autistic disorder in children are
      discussed. DSM-IV diagnostic criteria are presented. Usefulness of clinical
      interview and clinical experiment in diagnosing autistic disorder are analyzed.

PMID- 9527683
TI  - [Body image disturbance in anorexia nervosa].
AB  - 30 girls aged 13-19, who met DSM-IV criteria for anorexia nervosa, and control
      group were investigated by using: 1. semistructured interview with subjects and
      their mothers about the pubertal status, history of marked overweight and the
      teasing about weight, the discrepancy between actual and ideal body weight, 2. a
      specially prepared questionnaire aimed to establish onset of body image
      disturbances, and the connection with above-mentioned symptoms and life events
      and lowered self-esteem, 3. Hamilton Anxiety Scale and 4. subscale from the
      Eating Disorders Inventory--Body Dissatisfaction Scale. Body image disturbances
      were characterized for anorectic persons with low global self-esteem and high
      level of anxiety, and developed during the change of the peer group or a change
      of the patient's position within the peer group.

PMID- 9527685
TI  - [Obsessive-compulsive disorder in children and adolescents: literature review.
      Part I].
AB  - The literature on obsessive-compulsive disorder (OCD) in children and adolescents
      is reviewed. The disorder is characterized by obsessions (recurrent troublesome
      thoughts) and compulsions (ritualized thoughts or behaviors performed
      repetitively in response to an irresistible urge). OCD is far more common among
      children and adolescents than was previously believed. Good epidemiological
      studies from different parts of the world are still needed to determine if
      prevalence is equally high. Boys seem to have an earlier age of onset of OCD than
      girls. Male female ratio changed with age of onset, with males predominating in
      early onset and increasing numbers of females occurring during adolescence.
      Increasing evidence supports a neurobiological theory for etiology of OCD,
      specifically a frontal lobe--basal ganglia dysfunction.

PMID- 9527684
TI  - [Anorexia nervosa in a young man: a case report].
AB  - The paper describes a case of a young man with anorexia nervosa. We try to
      explain our difficulties in diagnosis and treatment of this patient. Most of them
      were connected with comorbidity of anorexia nervosa (depression, anxiety and
      obsessive-compulsive behaviour).

PMID- 9527686
TI  - [Efficacy assessment of fluoxetine treatment of outpatients with obsessive
      compulsive disorder: a preliminary report].
AB  - 20 obsessive-compulsive patients (OCD according to DSM IV) were treated with
      fluoxetine. The efficacy of the 3-month treatment was evaluated by Yale-Brown
      Obsessive Compulsive Rating Scale (Y-BOCS). The average of the Y-BOCS was 26.9 at
      the beginning of the treatment. The intensity of the OCD was radically lower
      after the first month of the treatment. The average of the Y-BOCS was 26.9 at the
      beginning of the treatment. The intensity of the OCD was radically lower after
      the first month of the treatment. The average of the Y-BOCS was 18.7 (difference
      statistically significant). The similar difference of the intensity of OCD was
      noticed after the second month of the treatment with fluoxetine. The average of
      the Y-BOCS was 12.9 (difference statistically significant). The average of the Y
      BOCS after the third month of treatment with fluoxetine was only 9.1. The
      intensity of OCD after 3 months of treatment with fluoxetine was clinically
      insignificant in 60% of the patients and in 35% it was mild. The result of the 17
      item Hamilton Depression Scale was low and was not changed statistically during 3
      months, treatment with fluoxetine. The results confirm the antiobsessional
      activity of fluoxetine, particularly in the second month of the treatment.
      Fluoxetine can be very useful in the treatment of OCD.

PMID- 9527687
TI  - [Panic disorder. Recent concepts of etiology and diagnosis].
AB  - In the light of recent research, panic disorder, for many years considered to
      have biological etiology, seems to be psychologically conditioned. The
      psychological part of etiology consists of distorted cognitive interpretation of
      somatic and emotional symptoms, which lead to the phenomenon of "fear of fear".
      "Fear of fear" reinforces vulnerability to experience subsequent attacks and
      intensity of their symptoms. The research work described in the article changed
      the diagnostic attitude towards panic disorder, both in DSM IV (APA 1994) and ICD
      10 (WHO 1994). That change urges to search for new models of psychotherapy,
      specific to panic disorder.

PMID- 9527688
TI  - [Nonpharmacological treatment of panic disorder in a situation of crisis and
      emergency].
AB  - The article provides a brief review of a number of the theories of panic and
      nonpharmacological interventions. In addition, the mention of pharmacological
      agents as well as ancillary suggestive techniques are also made in combination
      with the above.

PMID- 9527689
TI  - [Relationships in families of depressed patients].
AB  - There is evidence that many depressed adults come from dysfunctional families.
      What dominates in our sample of patients treated for endogenous depression is
      adverse early family environment, especially relationship with father. Mother is
      described as hopeless and overprotective. Such description of a patient's family
      may cause--according to the cognitive model of depression--dysfunctional thinking
      style.

PMID- 9527691
TI  - [Knowledge and beliefs on breast cancer and early detection practices among older
      women in Puerto Rico].

PMID- 9527692
TI  - [Ethical implications of new reproductive techniques].

PMID- 9527690
TI  - [Cortisol secretion rate 16 hours after dexamethasone administration in patients
      with major depression].
AB  - Plasma cortisol level was measured 7 times between 3 and 5 pm in 34 inpatients
      with major depression and 25 controls. 1 mg of dexamethasone per os was
      administrated the day before a 11 pm. The maximum, minimum, mean and range of
      cortisol concentration were calculated. All these parameters were statistically
      significantly higher in the depressed group.

PMID- 9527693
TI  - [Ethics and civilization: notes for the Third Millennium].

PMID- 9527694
TI  - [1st Symposium of Latin American Investigators of Biomedical Sciences. San Juan
      de Puerto Rico, 15-20 November 1996. Abstracts].

PMID- 9527695
TI  - [Expression of cathepsin D in breast cancer and its clinical and
      histopathological correlations].
AB  - BACKGROUND: Cathepsin D is a lysosomal protease which is overexpressed in some
      cases of breast cancer. Several studies done in tumor cytosol have shown that
      high levels of cathepsin D are associated with poor prognosis in patients with
      breast cancer but the results are not conclusive using immunohistochemistry
      methods to assay cathepsin D. OBJECTIVE: To evaluate if cathepsin D, assayed by a
      immunohistochemical technique using a polyclonal antibody, can be considered an
      independent prognostic factor in breast cancer. PATIENTS AND METHODS: Paraffine
      embedded sections of 68 tumor specimens from breast cancer patients in stages I
      to IV seen at the Instituto Nacional de Cancerologia during the period from 1985
      to 1986. RESULTS: From the 68 patients, 35 (51%) had an intense positive staining
      for cathepsin D, 19 (28%) han mild staining and 14 (21%) were negative. Ten
      patients with mild staining had artifacts due to deficiencies in the tissue
      fixation technique. Cathepsin D expression did not have a prognostic value nor
      association with other clinical and histopathological prognostic factors well
      established in breast cancer. CONCLUSION: Cathepsin D determined by
      immunohistochemistry has no prognostic value in breast cancer.

PMID- 9527696
TI  - [Bibliometric repercussions of adopting English as the sole language for
      publication].
AB  - OBJECTIVE: To determine the effect that the change from French to English had on
      the impact of the Annales de l' Institut Pasteur. THEORETICAL REFERENCE: The
      Pasteur Institute journals have a prestige of over 100 years of existence and
      eight Nobel Prize winners in Physiology and Medicine. Changes through time on the
      impact of these journals can be monitored as they are included in databases of
      the ISI (Institute for Scientific Information). METHODS: A year by year analysis
      from 1974 to 1992 was done using simple regression between percentage of articles
      published in English and: a) their impact factor; b) their ranking among journals
      of the same field. RESULTS: The determination coefficient (r2) between the
      percentage in English and the impact factor was 0.108, and that between
      percentage in English and the journal's rank in similar publications was 0.178
      for the Ann Microbiol, 0.045 for the Ann Immunol and 0.122 for the Ann Virol.
      CONCLUSIONS: The change of language did not increase the impact factor of the
      French journals.

PMID- 9527697
TI  - [99m-Tc alendronate as a new option in bone gammagraphy].
AB  - OBJECTIVE: To compare the quality of bone scans obtained with 99mTc-ABP, a new
      radiopharmaceutical, and 99mTc-MDP. MATERIAL AND METHODS: A comparative study
      within subjects was done in nine healthy volunteers, 5 female and 4 male, aged 23
      to 39 years. The dose for both radiopharmaceuticals was 740 MBq;
      radiopharmacokinetic parameters were determined and a whole body bone scan was
      taken with a MultiSpect 2 gamma camera two hours post administration with a wash
      out period of 72 hours between preparations. The images were independently
      evaluated by three nuclear medicine physicians by drawing of regions of interest
      (ROIs) on vertebrae, ribs, femur, sternum, joints and skull. Ratios bone/soft
      tissue were obtained drawing ROIs on several bones. The kappa test and the
      Wilcoxon rank test were used for statistical comparisons. RESULTS: The agreement
      on the quality of the images with Tc-ABP and Tc-MDP was fair (kappa 0.4). The
      femur/soft tissue ratio had a normal distribution and the Wilcoxon test showed no
      statistical difference between preparations. CONCLUSIONS: Even though bone uptake
      was higher and faster with Tc-ABP, the quality of the scans obtained with either
      radiopharmaceutical was similar. We recommend the use of Tc-ABP as a routine bone
      scan agent because of its less radiation exposure to the patient.

PMID- 9527698
TI  - [Measuring the impact of medical interventions at the individual level].
AB  - Medical interventions have a variable response among individuals. It is desirable
      to detect patients who are getting a therapeutic benefit. Any medical
      intervention has to show a favorable effect in survival and/or control of
      symptoms in order to be considered useful. In many clinical scenarios, laboratory
      test results are not enough to be confident of the effectiveness of a treatment.
      In order to do a clinical evaluation focused on patients' interests, we suggest
      the use of instruments to measure quality of life. Currently there are quality of
      life scales that have undergone a rigorous process of validation and reliability.
      Sub-group analysis is frequently used to predict an individual benefit of medical
      interventions. In the interpretation of sub-group analysis, it is important to be
      aware of the risk of misinterpretation, making false positive or false negative
      conclusions about the effect of the treatment. The N-of-1 trial is a valid
      scientific alternative to define individual effectiveness of therapy. Defining
      the degree of therapeutic benefit timely we avoid useless therapies, unnecessary
      side effects, and sequelae secondary to the lack of opportune treatment.

PMID- 9527700
TI  - [Gene therapy].
AB  - In the last years there has been much progress in our understanding of molecular
      mechanisms in the pathogenesis of disease. In this review we provide an overview
      of gene therapy, its most actualized techniques for gene delivery, and we give
      specific examples of laboratory and clinical achievements to date. The
      development of methods for delivering genes to mammalian cells has stimulated
      great interest in the possibility of treating human disease by gene-based
      therapies. As a result, concepts and methods that would have been considered
      purely science fiction 50 years ago are now used in the treatment of diseases.
      The widespread application of gene therapy technology to many diseases is already
      breaking down the traditional boundaries of modern medicine. However, despite its
      progress, several key technical drawbacks need to be overcome before gene therapy
      can be used safely and effectively in clinical settings. Technological
      developments, particularly in the areas of gene delivery and cell
      transplantation, will be critical for the successful practice of gene therapy.

PMID- 9527699
TI  - [Soft-drinks and health].
AB  - OBJECTIVE: To analyze published papers about soft drinks use, and to describe
      possible health benefits, risks, and damages related to soft drink consumption.
      INFORMATION SOURCE: A search was done in the MEDLINE compact disks, from January
      1970 to January 1997, with the keywords soft drink, beverages, carbonated
      beverages, cola, Coca-Cola and sweetening-agents. STUDY SELECTION: Ninety nine
      papers reporting health-related damages or benefits in clinical or experimental
      studies were reviewed. DATA EXTRACTION: All articles with a clear description of
      at least one beneficial or harmful effect related to soft drink consumption were
      considered. RESULTS: There were reports on 25 harmful effects and of 7 possibly
      beneficial effects. Data are classified in prophylactic and therapeutic uses,
      dental caries and other dental disorders, mineral metabolism disorders, acid
      peptic disease, neoplasm, risk factors for cardiovascular disease, effects on
      central nervous system, reproduction, allergy, and miscellaneous. CONCLUSIONS:
      High prevalence of exposure and excessive consumption of soft drinks may
      represent a public health problem in Mexico. Data analysis shows that soft drink
      consumption may not be as harmless as generally believed. Many of the reports are
      anecdotal, without a suitable methodological design. A wide field for research is
      present in this area.

PMID- 9527702
TI  - [Molecular biology in medicine. XI. The Human Genome Project].

PMID- 9527703
TI  - [The problem of switching to English].

PMID- 9527701
TI  - [New concepts in anionic and cationic amino acid transport].
AB  - In mammalian cells, amino acids are taken up by different transport systems
      present in the plasma membrane. The transport systems were originally
      characterized by kinetic and competition studies. However, it was difficult to
      assign specific amino acids to specific transport systems. With recent advances
      in molecular biology, it has been possible to identify the specific transporter
      proteins for specific amino acids. In this review we describe the anionic and
      cationic amino acid transport systems reported at the molecular level. The
      anionic amino acids are movilized mainly by the XaG- and Xc- systems which are
      important in the inactivation of glutamatergic nervous transmission in the brain
      and for the synthesis of glutathione, respectively. Four isoforms of the XAG-
      system in the brain belong to the family of Na+ dependent amino acid
      transporters. Transport systems for cationic amino acids also recognize
      zwitterionic substrates, and the better characterized systems at the present time
      are y+, y+L, bo,+ and Bo,+. The regulation of the entrance of cationic amino acid
      such as arginine, lysine, and ornithine to the cell is important in the
      biosynthesis of nitric oxide, creatine, carnitine, and polyamines. An inherited
      defect associated to bo,+ system is cysteinuria.

PMID- 9527704
TI  - [The ethics of public health service].

PMID- 9527705
TI  - [Ethics in medicine: a contribution from theology?].

PMID- 9527706
TI  - [Fundamental reflections on medical ethics--from the philosophical viewpoint].

PMID- 9527707
TI  - [Medical ethics--from the viewpoint of the practicing physician].

PMID- 9527708
TI  - [Fundamental reflections on medical ethics from the nurse's viewpoint].

PMID- 9527709
TI  - [The viewpoint of a former patient. The associations with medical ethics].

PMID- 9527710
TI  - [Cerebral SPECT and neuropsychological function in Alzheimer's disease].
AB  - In order to evaluate the relationship between perfusion brain SPECT and specific
      cognitive functions as well as the possible influence of the illness severity on
      them, 34 patients clinically diagnosed as probable Alzheimer disease (AD) and 12
      elderly controls were studied. AD patients were subdivided according to severity
      as 16 mild AD and 18 moderate AD. Neuropsychological battery of CERAD protocol
      and a semiquantitative analysis of 99mTc-HMPAO-SPECT images was carried out in
      all groups. With regard to the regions affected in SPECT, involvement of temporo
      parietal cortex were of most use in discriminating between AD patients and
      controls, but only temporal hipoperfusion distinguished mild disease from
      controls. Memory and praxis impairment correlated with temporo-parietal
      perfusion. Frontal involvement seemed to be a discriminator of disease
      progression, nevertheless, a significant correlation was present between memory
      and frontal hipoperfusion indicating the diffuse and sometimes heterogeneous
      distribution of AD pathology.

PMID- 9527711
TI  - [The entorhinal cortex (hippocampal formation) in aging and Alzheimer's disease.
      Neuroanatomical interpretation].
AB  - This paper deals with the neuronal changes shown by the entorhinal cortex in
      aging (30 cases) and in Alzheimer's disease (17 cases). In both instances,
      changes show a neuronal loss (measured as an index of cortical atrophy). The
      entorhinal cortex more closely related to polymodal association cortex hardly
      shows any variation with age, while Alzheimer cases present very intense neuronal
      loss. This pattern is interpreted taking into account the present knowledge about
      the connectivity of the entorhinal cortex and the remainder of the hippocampal
      formation and their role in memory processing.

PMID- 9527713
TI  - [Alzheimer's disease].

PMID- 9527712
TI  - [Mechanisms of cell death in Alzheimer's disease].
AB  - Molecular mechanisms involved in neuronal degeneration in Alzheimer's disease
      remain still unknown. A toxic effect induced by beta amyloid, oxidative stress,
      excitotoxicity and alterations in signal transduction mechanisms are the main
      factors linked to neuronal death. In addition, it has been suggested that
      apoptosis may also participate as a part of the cascade of events resulting in
      neurodegeneration.

PMID- 9527714
TI  - [Pathogenesis of Alzheimer's disease].
AB  - Alzheimer's disease (AD) is a multifactorial entity with a complex pathogeny.
      Recent findings on this subject are discussed in this article, centering mainly
      on genetic factors, cerebral ischemia and their association with the most typical
      histologic lesions in AD. Finally, a hypothetical model is proposed, in which
      beta-amyloid represents the key element.

PMID- 9527715
TI  - [Tacrine].
AB  - Significant changes in cholinergic neurotransmission have been described in
      Alzheimer's disease (AD). These findings led to consider cholinergic deficit as
      the main disturbance in AD, due to degeneration of presynaptic cholinergic
      neurons, and that replacement of acetylcholine could restore the cognitive
      alterations characteristic of AD. Although it was soon demonstrated that
      cholinergic deficit was not the only change, cholinergic hypothesis has allowed
      to set several possible therapeutic strategies for these severe disease, the most
      promising is administration of acetylcholinesterase inhibitors. Of all the
      compounds investigated, tacrine (tetrahydroamineacridine) has shown in several
      clinical trials a positive effect on memory in patients with symptoms of slight
      to moderate severity. Although not all studies have given successful result,
      probably due to methodological differences, global clinical impression has
      justified the introduction of tacrine as the first palliative therapy in AD.

PMID- 9527716
TI  - [Detection of early cases of Alzheimer's disease. Application of the CERAD
      neuropsychological test battery].
AB  - We attempt to determine the utility of CERAD in detecting early Alzheimer's
      disease (AD). CERAD battery was administered to a group of 14 control subjects,
      12 patients with possible dementia prodromes and to patients with Alzheimer's
      disease stratified according to severity (16 mild, 8 moderate). Other measures as
      some subtest of the Wechsler memory scale and the Rey Complex Figure Test were
      also applied. Delayed recall as well as logical memory of Wechsler memory scale
      were found to be the best discriminators for detecting very mild cases of AD
      (Prodromes) (p < 0.05). None of the memory test proved of value in staging the
      disorder. Visuospatial functions are better determinants of the progression of
      the illness. Fluency also distinguish between control subjects and very mild
      cases. These findings suggest that delayed recall memory and probably executive
      function are the most useful and sensitive indicators of Alzheimer's disease.

PMID- 9527718
TI  - Closing the book. Are power-line fields a dead issue?

PMID- 9527717
TI  - [Caregivers and care for patients with Alzheimer-type dementia].

PMID- 9527720
TI  - Fibromyalgia syndrome--An Interdisciplinary Challenge of Basic and Clinical
      Science. International conference. Bad Nauheim, Germany, October 23-25, 1997.
      Abstracts.

PMID- 9527719
TI  - [Brucellosis].

PMID- 9527721
TI  - [Morphological study of Enterocytozoon bineousi in patients with AIDS and chronic
      diarrhea].
AB  - Microsporidia are protozoan parasites responsible for significant
      gastrointestinal disease in patients infected with the human immunodeficiency
      virus. We report the clinical features of three patients with chronic diarrhea
      and intestinal microsporidiosis caused by Enterocytozoon bieneusi. The average
      value for CD4 in these patients was < or = 50 cells/mm3. The spores were detected
      in smears from stool samples and duodenal aspirates stained with trichrome blue
      in all patients. Light microscopy of semi-thin plastic sections revealed
      parasites and spores in the enterocytes and were associated with villous atrophy
      (2 out of 3). Thin section-electron microscopy showed a variety of developmental
      stages of the microsporidio. Patients treated with Albendazole had an
      unsatisfactory clinical response to therapy. Enterocytozoon bieneusi infection
      may be an important cause of diarrhea in patients with AIDS in our country.

PMID- 9527722
TI  - [Multicenter study of Helicobacter pylori infection prevalence in patients with
      chronic gastroduodenal disease. Various epidemiologic features].
AB  - The aim of this study was to establish the prevalence of H. Pylori infection in
      patients with chronic gastroduodenal pathology, who were treated in the
      gastroenterology units of four hospitals located in the Federal Capital and its
      neighbouring areas. 398 patients were studied by means of clinical assessment and
      epidemiology data. Upper endoscopy was carried out two biopsies were taken of the
      gastric antrum for a quick ureasa test and histological assessment of the H.
      pylori state by means of giemsa's stain. The prevalence of infection on the total
      of the studied population was 75.6%. In patients with gastric ulcer was 70%; in
      patients with duodenal ulcer it was 77.2% and 78.5% in patients with chronic
      gastritis. The prevalence of H. Pylori infection on the population according to
      age groups was: 61.54% in patients between 21 and 40 years; 76.14% in patients
      between 41 and 60 years, and 68.22% in patients over 60 year. We have tried to
      obtain a correlation between the prevalence of the infection and some sanitary
      characteristic (Running water and sewers) on the studied population. It was seen
      that 225 patients who lived in dwellings with running water and sewers showed a
      prevalence of infection of 69.34% and in 129 patients who did not have running
      water or sewer the rate of prevalence of infection was 83.72; a difference which
      was statistically significant, (with P < 0.01) for the patients who lived in poor
      sanitary conditions. These data may be important when the design of therapeutic
      schemes for the eradication of the bacteria is made.

PMID- 9527723
TI  - [Evaluation of sensitivity, specificity and predictive value of six qualitative
      serological methods for the detection of Helicobacter pylori antibodies].
AB  - Screening tests for IG g antibodies against Helicobacter pylori are usefull for a
      long follow up of patients who were well eradicated. The aim of this study was to
      determinate and compared sensibility, specificity, positive and negative
      predictive value of six qualitative serological tests for IG g antibodies
      detection in the diagnosis of H. Pylori infections. Between May and October 1996
      52 patients (30 males and 22 females; median age 42.4 years, range 21-68) with H.
      Pylori infection assessed on two antral and two corpus biopsies by means of Giema
      stain and a rapid urease test were tested for IG g antibodies detection. The
      serological tests used were: Inmunocomb II (Orgenics) Enzimo Inmuno Assay
      Inmunoadsorbent qualitative, Flex Pack (Smith Kline Diagnostics, Abbott)
      inmunocromatographic cualitative, Pylori Stat test (Biowhittaker) Enzimo Inmuno
      Assay (ELISA) qualitative, Premier (Meridian Diagnostics) Enzimo Inmuno Assay
      ELISA) qualitative. Pyloristest (Orion Diagnostica) latex aglutination
      qualitative, H. Pylori (Bio Tre) Enzimo Inmuno Assay cualitative. 10 healthy
      subjects with negative gastric biopsies and negative rapid ureasa test were used
      as control group. The six evaluated serological tests have a comparable
      sensibility (89-95%) and specificity (77-83%) for the diagnosis of HP infection.
      The presence of specific HP antibodies in infected patients revealed a strong
      correlation with the histological demonstration of the microrganisms. We can
      recommend this qualitative serological tests due to their high sensibility and
      specificity, simplicity and low cost.

PMID- 9527724
TI  - [Gastrointestinal autonomic tumor associated with von Recklinghausen's disease].
AB  - Gastrointestinal autonomic nerve (GAN) tumor is a rare type of gastrointestinal
      stromal tumor that is presumed to arise from the enteric autonomic plexus.
      Occasionally it develops associated with von Recklinghausen's disease (VRD). A 63
      year-old-woman with VRD and two GANs in the ileum is reported, and the literature
      of this combined findings reviewed.

PMID- 9527725
TI  - [Chronic intestinal pseudoobstruction caused by jejunal diverticulum. Report of a
      case and review of the literature].

PMID- 9527726
TI  - [Gargantua and digestive bariatric surgery].
AB  - Morbid obesity significantly reduces life span and is associated with much co
      morbid pathology. Diet, behavioral therapy and drugs therapy are largely
      unsuccessful, however the surgical treatment offers the best hope. This historic
      review about the bariatric surgery summarizes the jejuno ileal by-pass and the
      gastric surgery as the gastric bypass and the horizontal or vertical
      gastroplasties. Procedures that reduce gastric capacity and dietary in take are
      now considered preferable to those that alter food absorption as they are
      associated with fewer side-effects. The vertical banded gastroplasty is probably,
      the best operation for modern Gargantua's men.

PMID- 9527727
TI  - [Irritable bowel syndrome and other functional disorders. Is it time to change
      the focus?].

PMID- 9527728
TI  - [Helicobacter pylori: practical value of serology].

PMID- 9527729
TI  - Redox/radical repertoire rapport: pathophysiology and therapeutics.

PMID- 9527730
TI  - Propofol sedation and gastric emptying in volunteers.
AB  - BACKGROUND: The purpose of this study was to evaluate the effects of light
      propofol sedation on gastric emptying and orocecal transit time (OCT). METHODS:
      Ten healthy male volunteers were studied on 2 occasions separated by at least 1
      week and were randomly allocated to receive either propofol sedation or i.v.
      saline as a control. During propofol sedation the volunteers were sedated to
      grade 2-3 on a 5-grade scale. This was achieved by a propofol infusion of 5 mg
      kg(-1) h(-1) initially, which was then titrated down to a dose of 2.4+/-0.7 mg
      kg(-1) h(-1). Paracetamol absorption was used as an indirect measure of the rate
      of gastric emptying and OCT was determined by use of the hydrogen breath test
      after ingestion of raffinose. Student's t-test for paired samples was used and
      the results are presented as means+/-SD. RESULTS: During propofol sedation the
      maximum concentration of paracetamol (Cmax) was 115+/-26.8 micromol/L, time to
      peak concentration (Tmax) 50+/-38.8 min, and the area under the curve during the
      first 60 min (AUC60) 4793+/-1538 micromol x min/L, versus Cmax 99+/-20.8, Tmax
      69+/-41.9 and AUC60 3897+/-1310 during saline infusion. These differences were
      not statistically significant. OCT was significantly shorter during the control
      study, 180+/-32.4 min, than during propofol sedation, 217+/-64.9 min (P<0.05).
      CONCLUSION: This study in volunteers has shown that gastric emptying of liquids
      seems uninfluenced by light propofol sedation. OCT was slightly prolonged during
      light propofol sedation.

PMID- 9527731
TI  - Desflurane versus propofol maintenance for outpatient laparoscopic
      cholecystectomy.
AB  - BACKGROUND: The aims of the study were to evaluate costs and clinical
      characteristics of desflurane-based anaesthetic maintenance versus propofol for
      outpatient cholecystectomy. METHODS: All 60 patients received ketamine 0.2 mg kg(
      1), fentanyl 2 microg kg(-1) and propofol 2 mg kg(-1) for induction. Ketorolac
      0.4 mg kg(-1) and ondansetron 0.05 mg kg(-1) +droperidol 20 microg kg(-1) was
      given as prophylaxis for postoperative pain and emesis, respectively. The
      patients were randomly assigned into Group P with propofol maintenance and opioid
      supplements, or Group D with desflurane in a low-flow circuit system. RESULTS:
      All the patients were successfully discharged within 8 h without any serious
      complications. Emergence from anaesthesia was more rapid after desflurane; they
      opened their eyes and stated date of birth at mean 6.4 and 8.4 min respectively,
      compared with 9.6 and 12 min in the propofol group (P<0.05). Nausea and pain were
      more frequent in Group D, 40% and 80% respectively; versus 17% and 50% in Group P
      (P<0.05). By telephone interview at 24 h and 7 d after the procedure, there was
      no major difference between the groups. With desflurane, drug costs per case were
      10 $ lower than with propofol. CONCLUSION: We conclude that desflurane is cheaper
      and has a more rapid emergence than propofol for outpatient cholecystectomy.
      However, propofol results in less pain and nausea in the recovery unit. Despite
      ondansetron and droperidol prophylaxis, there was still a substantial amount of
      nausea and vomiting after desflurane.

PMID- 9527732
TI  - Midazolam-flumazenil versus propofol anaesthesia for scoliosis surgery with wake
      up tests.
AB  - BACKGROUND: Wake-up tests may be necessary during scoliosis surgery to ensure
      that spinal function remains intact. METHODS: Intra- and postoperative wake-up
      tests were performed together with somatosensory cortical evoked potentials
      (SCEPs) monitoring in 40 patients randomized to either midazolam (M) or propofol
      (P) infusions for scoliosis surgery. Other anaesthetic medication was similar in
      both groups. At the surgeon's request, N2O was turned off and midazolam or
      propofol infusions were discontinued. In the M group, flumazenil was given in
      refracted doses. Patients were asked to move hands and feet. The test was
      repeated immediately after the end of surgery. RESULTS: The median intraoperative
      wake-up times were 2.9 min in the M group and 16.0 min in the P group. The
      respective postoperative wake-up times were 1.8 and 13.9 min. The quality of both
      intra- and postoperative arousals was significantly better in the M group. Twelve
      patients in the P group could not be awakened intraoperatively within 15 min and
      were given naloxone. One of these patients woke up violently and dislodged the
      endotracheal tube. Another patient in the P group had explicit recall of the
      test, but no pain. Five patients in the M group became resedated in the recovery
      room. Cost of anaesthetic drugs was similar in both groups. Satisfactory
      intraoperative SCEPs were recorded from 17 patients in each group. There were no
      neurological sequelae. CONCLUSIONS: Wake-up tests can be conducted faster and
      better with midazolam-flumazenil sequence compared with propofol.

PMID- 9527733
TI  - Oculocardiac reflex and postoperative vomiting in paediatric strabismus surgery.
      A randomised controlled trial comparing four anaesthetic techniques.
AB  - BACKGROUND: Oculocardiac reflex (OCR) and postoperative vomiting are major
      complications of paediatric strabismus surgery. METHODS: Children (3-16 yr)
      undergoing elective strabismus surgery as inpatients were randomly allocated to
      four anaesthetic techniques: (A) thiopentone induction and isoflurane
      maintenance; (B) as (A) plus ondansetron 5 mg x m(-2) i.v.; (C) propofol
      induction and maintenance; (D) as (C) plus lignocaine 2 mg x kg(-1) i.v. All
      children received prophylactic atropine 0.02 mg x kg(-1) and alfentanil. Nitrous
      oxide was omitted. RESULTS: Data on 157 children were analysed. The cumulative
      incidence of vomiting within 6 and 24 h after surgery with thiopentone-isoflurane
      was 26% and 46%, respectively. Adding ondansetron decreased the incidence to 8%
      and 33%, respectively. This improvement was significant within 6 h only; the
      number-needed-to-treat was 5.5 (95% CI 2.9-46). Propofol was not different from
      thiopentone-isoflurane. The addition of lignocaine to propofol was of no benefit.
      The risk of an OCR was significantly increased with propofol (incidence 40%)
      compared with isoflurane (14%); the number-needed-to-harm was 3.9 (95% CI 2.6-8).
      CONCLUSIONS: Thiopental-isoflurane-air/O2-alfentanil resulted in a moderate risk
      of vomiting. Adding ondansetron significantly decreased this risk, but 6 children
      have to be treated for one to benefit in the early postoperative period. Propofol
      and propofol-lignocaine showed no benefit on vomiting but significantly increased
      the risk of an OCR despite high-dose prophylactic atropine.

PMID- 9527734
TI  - Nausea and vomiting after major arthroplasty with spinal anaesthesia including
      morphine: a randomised trial of subhypnotic propofol infusion as prophylaxis.
AB  - BACKGROUND: Postoperative nausea and vomiting (PONV) following major arthroplasty
      with spinal anaesthesia and intrathecal morphine is reported in 45-74% of
      patients. This randomised, double-blind, placebo-controlled trial was undertaken
      to determine whether a subhypnotic infusion of propofol has a prophylactic
      antiemetic effect in this patient population. METHODS: 82 patients undergoing hip
      or knee replacement under subarachnoid bupivacaine anaesthesia plus morphine 0.25
      mg were randomised at the end of surgery to receive either propofol 30 mg x h(-1)
      or fat emulsion (Intralipid) 3 ml x h(-1) for 20 h postoperatively. Blinded
      observers recorded episodes of nausea, vomiting and pruritus. RESULTS: PONV in
      the intervention group was 40% vs 59% in the controls (P=0.1, not significant).
      Pruritus occurred in 34%, with a similar rate in both groups. CONCLUSION: These
      results suggest that routine use of postoperative, subhypnotic propofol infusion
      as PONV prophylaxis is not justified in this patient population.

PMID- 9527735
TI  - Air contamination of a closed anesthesia circuit.
AB  - Closed-circuit anesthesia (CCA) has certain advantages such as decreased cost,
      decreased anesthetic gas pollution, improved inhalational gas humidity and
      temperature in comparison to conventional inhalational anesthesia using a high
      fresh gas flow, i.e. more than 2 L x min(-1), with a semi-closed breathing
      circuit. The main disadvantage of CCA is the possibility of hypoxic anesthetic
      gas delivery. This potentially lethal situation is caused by an insufficient
      oxygen flow rate for the body metabolism or by the accumulation of inactive gas,
      usually nitrogen, within the breathing circuit in spite of a sufficient oxygen
      concentration in the fresh gas supply to the breathing circuit. In the latter
      case, the accumulation of inactive gas may also lead an increased risk of
      awareness because of its dilution effect on the concentrations of inhalational
      anesthetics. We herein present a case of air contamination of the breathing
      circuit through a sampling line of an anesthetic gas monitor. The air caused a
      decrease in the oxygen concentration during closed circuit anesthesia.

PMID- 9527736
TI  - Intraoperative monitoring with somatosensory evoked potentials in carotid artery
      surgery--less reliable in patients with preoperative neurologic deficiency?
AB  - BACKGROUND: In a retrospective analysis of intraoperative somatosensory evoked
      potential (SEP) results during carotid artery surgery we found some cases with
      postoperative neurologic deficits, surprisingly without significant SEP changes.
      METHODS: Median nerve SEP were monitored as usual. Indication for selective
      shunting was a complete loss of amplitude N20/P25 in the first period of the
      investigation, later on a 50% reduction, or a prolongation of the central
      conduction time (CCT) of about 1.5 ms after cross-clamping. Anaesthesia was
      maintained with isoflurane in N2O/O2, fentanyl and atracurium. RESULTS: Over a 3
      year period 146 patients were monitored. Indications were: transient ischaemic
      attacks (TIA) (n=51), stroke (n=23), stroke with residuals (n=39), asymptomatical
      stenosis (n=29), subclavian steal syndrome (n=4). Twenty-four patients received
      an intraluminal shunt following SEP alterations. Postoperatively, 5 patients
      (3.4%) had symptoms of intraoperative brain ischaemia (stroke n=2, TIA n=3), 4 of
      them showing only minor intraoperative SEP alterations; 1 received a shunt
      because of CCT prolongation. Four of these 5 patients had cerebral neurologic
      deficiency preoperatively. CONCLUSION: Since some authors have found a 100%
      sensitivity of intraoperative SEP, it is remarkable, that 1 patient with
      postoperative stroke and 3 patients with TIA had no significant SEP changes
      intraoperatively. We suppose there was an association with preoperative
      neurological deficits resulting from previous strokes. In such cases, regional
      critical ischaemia may apparently occur outside the sensory pathway monitored
      with SEP.

PMID- 9527737
TI  - Unilateral vocal cord paralysis following endotracheal intubation.
AB  - The present report describes a case of postoperative paralysis of the left
      recurrent laryngeal nerve in a patient undergoing surgery at a site far from the
      anatomic course of the nerve. Possible aetiological factors, symptoms, management
      and prophylaxis are discussed.

PMID- 9527738
TI  - Hemiballism-hemichorea from marked hypotension during spinal anesthesia.
AB  - Hemiballism and hemichorea following anesthesia-induced hypotension has rarely
      been described, but a recent case suggests an association. After experiencing
      marked hypotension during spinal anesthesia, a 70-year-old woman developed
      hemiballism and hemichorea. Involuntary ballistic movements with writhing,
      consisting of repetitive rotation and flexion-extension without apparent muscle
      weakness, affected her left limbs proximally. Low-amplitude, involuntary,
      choreiform movements involved the distal portions of these limbs. Magnetic
      resonance imaging demonstrated an area of high signal intensity in the
      contralateral subthalamic nucleus, suggestive of a focal ischemic lesion.
      Although such occurrences are rare, anesthesiologists should be aware of the risk
      of subthalamic nucleus ischemia following marked hypotension.

PMID- 9527739
TI  - Thyromental distance--shouldn't we redefine its role in the prediction of
      difficult laryngoscopy?

PMID- 9527741
TI  - Systemic oxygen uptake during experimental closed-chest cardiopulmonary
      resuscitation using air or pure oxygen ventilation.
AB  - BACKGROUND: Although clinical cardiopulmonary resuscitation always includes
      ventilation with pure oxygen, this kind of ventilation has been reported to be
      associated with worse neurological outcome than ventilation with air in
      experimental cardiopulmonary resuscitation (CPR). The aim of the present
      investigation was to compare the systemic oxygen uptake during experimental
      closed-chest CPR including ventilation with pure oxygen or ambient air and,
      furthermore, to elucidate possible mechanisms of action in the regulation of
      pulmonary gas exchange. METHODS: In 24 anesthetized piglets, 2 min of induced
      ventricular fibrillation and no ventilation was followed by 10 min of closed
      chest CPR including i.v. administration of 0.5 mg adrenaline (at 8 min), and in
      one of the experimental groups alkaline buffer (at 5 min). The piglets were
      randomly divided into 3 groups: air ventilation during the entire CPR period with
      saline administration (n=8), air ventilation during the entire CPR period plus
      tris buffer mixture (n=8), and air ventilation for 3 min followed by 100% oxygen
      with saline administration (n= 8). RESULTS: In the group ventilated with air and
      treated with tris buffer mixture, cardiac output was significantly greater than
      in the group ventilated with pure oxygen. The arterial-mixed venous oxygen
      content difference was approximately 25% greater with pure oxygen than with air
      ventilation; however, there was no difference in systemic oxygen uptake. Systemic
      oxygen uptake increased after administration of tris buffer mixture in the group
      ventilated with air. CONCLUSIONS: Pulmonary hypoxic vasoconstriction appeared to
      be abolished during CPR including pure oxygen ventilation. Blood flow, not
      ventilation or pulmonary gas exchange, is the limiting factor during experimental
      closed-chest CPR.

PMID- 9527740
TI  - Pituitary-adrenal, hormonal changes during induced hypotension with labetol or
      isoflurane for middle-ear surgery.
AB  - BACKGROUND: Pituitary-adrenal secretion during induced hypotension for middle-ear
      surgery has received little attention. Previous work failed to differentiate the
      effects of induced hypotension from surgical stimulation. We have undertaken a
      preliminary study examining the effects of hypotension, achieved with labetalol
      or isoflurane, on pituitary-adrenal secretion before, during and after middle-ear
      surgery. METHODS: Twenty-four patients were allocated randomly to 3 groups. The
      control group were anaesthetised with isoflurane, and normotension maintained for
      30 min before hypotension was induced with isoflurane and surgery started. In the
      labetalol group, this drug was given i.v. to obtain a mean arterial pressure
      (MAP) of 60 mm Hg for 30 min before surgery and hypotension maintained with
      labetalol during the operation. In the isoflurane group, hypotension was induced
      to a MAP of 60 mm Hg for 30 min before surgery and continued throughout the
      procedure. All 3 groups received metoprolol i.v. before hypotension was
      established. Blood samples were collected before induction of anaesthesia, during
      anaesthesia alone (normotensive or hypotensive), surgery with hypotension, and
      recovery. They were analysed for adrenocorticotropic hormone (ACTH), arginine
      vasopressin (AVP), cortisol and aldosterone. RESULTS: Induced hypotension before
      surgery failed to stimulate release of ACTH, AVP and cortisol. No significant
      increase in these hormones occurred until the postoperative period. Aldosterone
      concentrations increased significantly during anaesthesia and hypotension in the
      labetalol and isoflurane groups (P<0.05) and continued to rise significantly in
      all 3 groups during surgery. However, there was no significant difference in
      aldosterone concentration before surgery between the control and the 2
      hypotensive groups. CONCLUSION: ACTH, AVP and cortisol secretion were not
      stimulated by induced hypotension to MAP of 60 mm Hg before surgery. Increased
      aldosterone secretion occurred and a further study with a larger sample size is
      needed.

PMID- 9527742
TI  - Extra protein loss not caused by surgical bleeding in patients with ovarian
      cancer.
AB  - BACKGROUND: [corrected] Clinical experience in patients with ovarian cancer has
      shown special difficulties in maintaining cardiovascular stability during
      surgery. METHODS: To evaluate the causes for this observation, 15 patients with
      benign ovarian tumours (group I) and 13 patients with ovarian cancer (group II)
      were investigated perioperatively. Plasma volume (indocyanine green-dilution
      technique), haematocrit, plasma protein concentration, mean arterial pressure,
      heart rate, and central venous pressure were measured immediately before and
      after cytoreductive surgery. RESULTS: Normal values of blood-, plasma-, and red
      cell volume were determined preoperatively in both groups, and in relation to
      body surface area there were no intergroup differences of these parameters. In
      group I, the significant decrease in red cell volume of 313 ml postoperatively
      was compensated for by an increase in plasma volume of 371 ml (median values). In
      contrast to group I, the decrease in red cell volume of 328 ml in group II was
      not related to a significant increase in plasma volume, so that blood volume
      postoperatively was 483 ml lower than preoperatively, although the same
      standardized infusion regimen as in group I was applied. Patients of group II had
      a significantly higher loss of intravascular protein (49 g vs 13 g in group I),
      which left the intravascular space by another way than by surgical bleeding. This
      extra protein loss is termed Intraoperative Protein Shift (IPS). CONCLUSION: IPS
      could be an important quantity in perioperative fluid balance. We assume that
      different surgical procedures predispose to occurrence of differing amounts of
      IPS.

PMID- 9527743
TI  - In vitro study on antioxidant potential of various drugs used in the
      perioperative period.
AB  - BACKGROUND: Since surgical trauma not only intensifies the oxidative stress by
      generating reactive oxygen species (ROS), but also weakens the biological defense
      system against ROS attack, the antioxidant activity of drugs used during the
      perioperative period, which possibly normalizes the impaired redox state in the
      patient, is of fundamental importance and great clinical interest. METHODS: We
      have applied the phycoerythrin fluorescence-based assay, in which 2,2'-azobis (2
      amidinopropane) dihydrochloride (AAPH)-generated peroxyl radical attacks B
      phycoerythrin (B-PE) to lead to a sensitive decrease in its fluorescence
      intensity linearly, to evaluate the antioxidant activity of major drugs in
      anesthetic practice. RESULTS: By the protective effect on B-PE fluorescence
      decay, the antioxidant activities of the drugs were classified into three groups:
      Group I drugs, which only slowed B-PE fluorescence decay (nicardipine, verapamil,
      diltiazem, ephedrine, aminophylline, vecuronium, lidocaine, mepivacaine,
      midazolam, thiamylal, droperidol, ketamine, hydroxyzine, butorphanol,
      prednisolone, hydrocortisone, betamethasone, dexamethasone, methylprednisolone,
      and furosemide); Group II drugs, which protected B-PE oxidation completely and
      stopped fluorescence decay in a certain duration (dopamine, epinephrine,
      norepinephrine, dobutamine, isoproterenol, and buprenorphine); and Group III
      drugs, which had no protective effect on B-PE oxidation (nitroglycerin,
      prostaglandin E1, neostigmine, pancuronium, suxamethonium, atropine, bupivacaine,
      pentazocine, and heparin). CONCLUSION: These results indicate that Group I and II
      drugs exert some antioxidant activity in vitro, as measured by their protection
      of fluorescence decay of B-PE. Careful consideration of these properties might,
      then, serve to facilitate more efficient drug application.

PMID- 9527744
TI  - Parasympathetic activity in brain death: effect of apnea on heart rate
      variability.
AB  - BACKGROUND: Power spectral analysis of heart rate variability is a useful
      monitoring of brain-damaged patients. However, the effect of artificial
      ventilation is not clearly demonstrated in assessing vagal activity because the
      locus of its activity is originated close to the respiratory center in the brain
      stem. We studied heart rate variability during artificial ventilation and apnea
      test as part of an assessment of brain death. METHODS: Ten adult patients with
      severe brain damage were studied. Power spectral analysis of heart rate
      variability from electrocardiographic R-R intervals was integrated to compare
      spectral components before, during and after the apnea test. Before the test,
      circulatory and blood gas variables and electrocardiographic recording were
      obtained under controlled mechanical ventilation at a rate of 12 and 18 (/min),
      each for 5 min. Measurements were made for 10 min during the apnea test, and
      repeated thereafter as before the test. Power spectral analysis based on fast
      Fourier transformation was made by integrating each low- (LF: 0.04-0.15 Hz) and
      high- (HF: 0.15-0.40 Hz) frequency band areas. LF was assessed as sympathetic and
      parasympathetic nervous activity, and HF as respiratory-related parasympathetic
      vagal activity. The HF/LF ratio showed sympathovagal balance. RESULTS: All
      patients were assessed as brain dead. During apnea, PaCO2 (P<0.01) and LF
      (P<0.05) increased, and pH (P<0.01) and HF/LF ratio (P<0.05) decreased. Heart
      rate, mean arterial pressure, PaO2 and HF remained consistent throughout.
      CONCLUSION: It was shown that sympathovagal balance was inclined to be
      sympathotonic during apnea, and that there were no changes in the respiratory
      related vagal activity in spite of stopping artificial ventilation.

PMID- 9527745
TI  - Catheter-related infections following axillary vein catheterization.
AB  - BACKGROUND: The aim of this study was to determine the rate of infectious
      complications following axillary vein cannulation and to compare to that observed
      after internal jugular vein catheterization. METHODS: A prospective comparative
      open study was carried out to determine the rate of infectious complications
      related to the use of catheters inserted via the axillary vein or the internal
      jugular vein. During the study period all patients submitted to central venous
      catheterization were evaluated. A total of 141 patients entered and completed the
      study. Catheter insertion sites were either the axillary vein punctured in the
      axilla, or the internal jugular vein punctured using an anterior approach.
      Catheter tips were cultured using a quantitative technique. Clinical information
      pertaining to the analysis was prospectively collected. RESULTS: A total of 141
      catheters from 141 patients entered was studied. Clinical characteristics and
      risk factors for catheter infection were similar in both groups. The incidence of
      catheter-related infection (including catheter-related sepsis, and bacteremia)
      was not different between the two groups (axillary vein: 8.1%; internal jugular
      vein: 7.6%). Catheter-related bacteremia were seen at a rate of 3.7% in the
      internal jugular vein group and a rate of 1.6% in the axillary vein group (NS).
      The incidence of catheter colonization was similar in both groups (axillary vein:
      14.5%; internal jugular vein: 11.4%). CONCLUSION: Catheter-related infection
      after axillary vein catheterization was similar to that observed after internal
      jugular vein catheterization. The chance of developing catheter-related sepsis
      was less than 10% with either route when catheters were used for the treatment of
      severely ill patients.

PMID- 9527746
TI  - Haemolysis following rapid experimental red blood cell transfusion--an evaluation
      of two infusion pumps.
AB  - BACKGROUND: The vast majority of infusion pumps used for rapid transfusion of
      large amounts of blood have never been properly examined regarding their
      influence on the quality of the red blood cells (RBCs) infused. In this study, we
      evaluated the effect of two different infusion pumps on the degree of RBC
      destruction following rapid experimental blood transfusion. METHODS: Divided into
      2 groups according to age, 30 u of SAGM RBCs were infused through an experimental
      transfusion model by either a manual roller pump (MRP) or a pressure infusor pump
      (PIP). Fresh (i.e stored for 8-11 d) RBCs, 20 u, and 10 u of older (i.e. stored
      for 25-33 d) RBCs were randomly allocated to infusion with either of the two
      pumps. The rate of infusion was as fast as possible with the MRP, and with the
      PIP adjusted with an external applied pressure of 300 mm Hg. RBC samples
      collected before and after infusion were analyzed for total haemoglobin, free
      haemoglobin, haematocrit, total free potassium, lactate dehydrogenase (LDH) and
      the percentage of haemolysis. The time spent for each transfusion was measured by
      a stop watch. RESULTS: Following infusion, a marginal increase (i.e. considerably
      below 0.8%) in the percentage of haemolysis and LDH content was seen with both
      pumps. This increase was only statistically significant when RBCs stored for 8-11
      d were used (P = 0.002 for both parameters). Irrespective of the age of the RBCs,
      no differences between the two pumps could be detected. Compared to the PIP,
      infusion with the MRP could be accomplished significantly faster, i.e. median 5.9
      ml/s (5.2-6.4 ml/s) versus 2.9 ml/s (2.5-3.2 ml/s), (P < 0.0001). CONCLUSIONS:
      Both the pumps used in this study are safe alternatives for rapid transfusion of
      RBCs; however, with MRP this can be accomplished approximately twice as fast as
      with the PIP.

PMID- 9527747
TI  - Effects of anaesthesia based on high versus low doses of opioids on the cytokine
      and acute-phase protein responses in patients undergoing cardiac surgery.
AB  - BACKGROUND: Cardiac surgery with cardiopulmonary bypass (CPB) evokes a systemic
      inflammatory response involving the proinflammatory cytokines tumor necrosis
      factor-alpha (TNFalpha), interleukin (IL)-1, IL-6, IL-8 and anti-inflammatory
      cytokines such as IL-10. Like IL-10, opioids downregulate the immune responses in
      vivo and in vitro, including the activity of the cytokine-producing monocytes and
      granulocytes. The proinflammatory cytokines are potent inducers of the hepatic
      acute-phase protein synthesis. The aim of the present study was to investigate if
      choice of anaesthesia, based on high-dose opioids (fentanyl) versus low-dose
      opioids influenced the release of IL-6, IL-8, and IL-10. Secondly, it was
      investigated whether serum amyloid P-component (SAP) is an acute-phase protein in
      man such as C-reactive protein (CRP), with which it is physically and
      structurally related. METHODS: Sixteen patients submitted to elective coronary
      artery bypass grafting (CABG) surgery were randomized to either low-dose opioid
      anaesthesia consisting of thoracic epidural analgesia combined with inhalational
      anaesthesia (group I) or high-dose fentanyl anaesthesia (group II). From each
      patient 18 blood samples were taken perioperatively. Cytokine analyses were
      performed with ELISA, CRP and SAP mere measured with rocket immunoelectrophoresis
      (RIE). RESULTS: Surgery and CPB elicited a marked, transient and almost
      simultaneous proinflammatory and anti-inflammatory cytokine response with no
      differences between the groups. The cytokine levels returned to preoperative
      levels 1-3 d after operation. Anaesthesia and surgery did not affect SAP plasma
      levels while patients showed a major increase in CRP concentrations preceding the
      cytokine responses. CONCLUSION: CABG performed during two different anaesthetic
      techniques, high-dose fentanyl versus low-dose opioid anaesthesia, elicited a
      well-defined cytokine response with minor variation in the time course of each
      cytokine. The cytokine production was not modified by type of anaesthesia.
      Finally, SAP is not an acute-phase protein in men.

PMID- 9527748
TI  - Comparing analgesic efficacy of non-steroidal anti-inflammatory drugs given by
      different routes in acute and chronic pain: a qualitative systematic review.
AB  - AIM: To test the evidence for a difference in analgesic efficacy and adverse
      effects of non-steroidal anti-inflammatory drugs (NSAIDs) given by different
      routes. METHODS: Systematic review of published randomised controlled trials.
      Relevant trials were comparisons of the same drug given by different routes.
      Presence of internal sensitivity was sought as a validity criterion. Analgesic
      and adverse effect outcomes were summarised, and synthesised qualitatively.
      RESULTS: In 26 trials (2225 analysed patients), 8 different NSAIDs were tested in
      58 comparisons. Fifteen trials (58%) compared the same drug by different routes.
      Drugs were given by intravenous, intramuscular, intrawound, rectal and oral
      routes in postoperative pain (14 trials), renal colic (4), acute musculoskeletal
      pain (1), dysmenorrhoea (1), and rheumatoid arthritis (6). Five of the 15 direct
      comparisons were invalid because they reported no difference between routes but
      without evidence of internal sensitivity. In all 3 direct comparisons in renal
      colic, intravenous NSAID had a faster onset of action than intramuscular or
      rectal. In 1 direct comparison in dysmenorrhoea, oral NSAID was better than
      rectal. In the 5 direct comparisons in postoperative pain, results were
      inconsistent. In 1 direct comparison in rheumatoid arthritis, intramuscular NSAID
      was better than oral. Injected and rectal administration had some specific
      adverse effects. CONCLUSION: In renal colic there is evidence that NSAIDs act
      quickest when given intravenously. This may be clinically relevant. In all other
      pain conditions there is a lack of evidence of any difference between routes. In
      pain conditions other than renal colic, there is, therefore, a strong argument to
      give oral NSAIDs when patients can swallow.

PMID- 9527749
TI  - Cardiovascular effects of two different regional anaesthetic techniques for
      unilateral leg surgery.
AB  - BACKGROUND: Cardiovascular function was assessed in 20 ASA I-II patients,
      scheduled for elective orthopaedic surgery with tourniquet in order to compare
      the haemodynamic changes induced by unilateral spinal anaesthesia and combined
      sciatico-femoral nerve block. METHODS: After baseline measurement of
      cardiovascular parameters, patients were randomized to receive unilateral spinal
      anaesthesia or combined sciatico-femoral nerve block. Spinal anaesthesia was
      obtained by 8 mg of hyperbaric bupivacaine 0.5% slowly injected (speed=0.02 ml s[
      1]) through a 25-G Whitacre spinal needle with the bevel orientated towards the
      dependent side and patients lying on their operated side for 15 min (group S,
      n=10). Combined sciatico-femoral nerve block was obtained by 7 mg kg(-1) of
      mepivacaine 2% (group NB, n=10). Haemodynamic variables were recorded 5, 10, 15,
      and 30 min after anaesthetic injection before surgery was started. RESULTS:
      Anthropometric data, duration of surgery and acceptability of anaesthetic
      techniques were similar in the 2 groups. In 8 patients of group S, spinal block
      was restricted to the operated side (pinprick test and Bromage scale), while the
      other 2 patients developed bilateral spinal block after being turned supine. NB
      patients showed no haemodynamic changes during the study, whereas patients in
      group S showed a small but significant decrease of mean arterial blood pressure
      (P<0.002 vs baseline and P<0.04 vs NB), cardiac index (P<0.01 vs baseline and
      P<0.01 vs NB), and stroke volume index (P<0.01 vs baseline and P<0.01 vs NB).
      CONCLUSION: Both sciatico-femoral and unilateral spinal blockade provide adequate
      anaesthesia for unilateral leg surgery with tourniquet. The former technique
      affects cardiovascular performance less than the latter one.

PMID- 9527750
TI  - Effects of high thoracic epidural anaesthesia on the peripheral airway reactivity
      in dogs.
AB  - BACKGROUND: It has been speculated that epidural anaesthesia may induce
      bronchoconstriction via the mechanism of a sympathetic blockade. However, this
      hypothesis has not been confirmed by any experimental evidence. Therefore, we
      investigated the effects of high thoracic epidural anaesthesia with neural
      sympathetic blockade on basal airway resistance and airway reactivity in response
      to bronchoconstrictive stimuli in a canine periphery lung model. METHODS:
      Acetylcholine (Ach, 8 microg kg[-1] i.v.) or histamine (His, 3 microg kg[-1]
      i.v.) was administered to 7 anaesthetized mongrel dogs before and after thoracic
      epidural anaesthesia. Successful neuronal sympathectomy was confirmed by
      nitroglycerin test. The changes of peripheral airway resistance (Rp),
      haemodynamics, cardiac output (CO), and the recovery time for Rp from peak
      returning to baseline in each challenge were studied. RESULTS: Thoracic epidural
      anaesthesia altered neither the baseline Rp nor the peak Rp evoked by Ach or His.
      However, the recovery time of the Rp was prolonged significantly after epidural
      anaesthesia (P<0.01) and correlated inversely with the CO in response to Ach or
      His challenge (Ach, r=0.542; His, r=0.651). CONCLUSIONS: Our results suggest that
      epidural anaesthesia with neural sympathetic blockade has no influence on the
      basal peripheral airway resistance; however, it prolongs the airway reactivity to
      Ach or His challenge, probably by the mechanism of reducing CO.

PMID- 9527751
TI  - Patients' desire for information about anaesthesia: Danish attitudes.
AB  - BACKGROUND: Patients' desire for information about anaesthesia has been examined
      in a number of Commonwealth countries but not in Scandinavia. A questionnaire was
      distributed to form a basis for giving Danish patients more appropriate
      preoperative information. METHODS: 201 preoperative patients in Denmark were
      asked to complete a questionnaire. The patients were divided into subgroups
      according to: age, gender, residential origin, ASA group, educational level, type
      of anaesthesia planned and number of previous anaesthetics. RESULTS: Patients
      from a city area required significantly more information than patients from a
      rural/urban area about premedication drugs, drips/catheters, pain/pain relief and
      complications. Men more than women preferred to know about dangerous
      complications. Information about pain/pain relief, duration of anaesthesia, and
      influence of anaesthesia on daily activities such as eating, drinking,
      mobilisation was given the highest priority, while unpleasant information such as
      about complications and needles was given the lowest priority. Meeting the
      anaesthetist and information about alternative methods of anaesthesia and
      premedication drugs were given only moderate priority. Ranking information in
      Denmark was significantly correlated with Scotland, Canada and Australia, despite
      profound differences in priority. More often than Danish patients, Australian
      patients felt they had right to know, and especially about complications.
      CONCLUSION: Patients from a city area required more information than patients
      from a rural/urban area. Information about the influence on daily activities was
      preferred to unpleasant information. Ranking information in Denmark was
      correlated with a number of Commonwealth countries.

PMID- 9527752
TI  - Preoperative anxiolysis with minimal sedation in elderly patients: bromazepam or
      clorazepate-dipotassium?
AB  - BACKGROUND: In elderly patients undergoing ophthalmic surgery the loss of co
      operation due to over-sedation, induced by drugs given preoperatively, may
      jeopardise the success of microsurgery performed under regional anaesthesia. The
      aim of this study was to compare the psychotropic effects of bromazepam and
      clorazepate-dipotassium, two benzodiazepines with predominantly anxiolytic and
      only weak sedative action. METHODS: A randomised, placebo-controlled, double
      blind study was designed to include 60 patients, ASA physical status II-III,
      older than 60 years scheduled for ophthalmic surgery under regional anaesthesia.
      The patients were randomised to receive either bromazepam (3 mg) or clorazepate
      dipotassium (20 mg) or placebo. The study drugs were given at 10 p.m. the night
      before surgery and 90 min before surgery. Using the State-Trait Anxiety Inventory
      (STAI), the patient's anxiety was assessed at the end of the preoperative visit,
      on the next morning before the study drug was given and on arrival at the
      operating theatre. RESULTS: Bromazepam induced a marked anxiolytic effect as
      documented by a significant reduction in the STAI State values after both
      applications (P<0.01). Clorazepate did not differ from placebo at any evaluation
      time with regard to the STAI and haemodynamic values. Sedative effects and oxygen
      saturation (SpO2) were comparable in all groups. CONCLUSION: Bromazepam is
      superior to clorazepate in its anxiolytic action and suitable as preoperative
      medication in the elderly patient because of lack of overt sedative effects.

PMID- 9527753
TI  - [Where does the Ridley and Jopling classification stand in 1997?].

PMID- 9527754
TI  - [New WHO recommendations for the treatment of leprosy].

PMID- 9527755
TI  - [Atypical presentations of leprosy: apropos of 2 cases].
AB  - This report describes two atypical cases of leprosy. A 48 year old male patient
      presented laryngeal dyspnea with adhesions of the oropharynx of which the
      biopsies were inconclusive. The patient was cachectic with hyperesthesia of the
      extremities and two subcutaneous nodules. The biopsy of one nodule evoked
      thesaurismosis or dyslipoidosis while the bacilloscopy was positive in nasal
      smears. A 14 year old female patient suffered from bullae which appeared
      spontaneously on erythematous skin on the legs and upper arms. Upon examination
      those areas were found to be hypoaesthetic, as was a very large hamartoma on the
      left half of the body. A biopsy of healthy skin evoked the diagnosis of leprosy.
      The patient then developed BT leprosy and episodes of hysteria. The first
      observation led to several diagnoses: while laryngeal dyspnea is unusual in LL
      and while cutaneous histology of regressive LL contrasted with the abundance of
      the bacilloscopy. The diagnosis of the second case is that of indeterminate
      leprosy with premonitory neurological signs associated with pathomania and
      evolution to a multibacillary form.

PMID- 9527756
TI  - In vivo detection of Trypanosoma cruzi antigens in hearts of patients with
      chronic Chagas' heart disease.

PMID- 9527757
TI  - Elongation of arthroscopically tied knots.

PMID- 9527759
TI  - Fibular grooving for recurrent peroneal tendon subluxation.

PMID- 9527758
TI  - Muscle rehabilitation after arthroscopic meniscectomy with or without tourniquet
      control.

PMID- 9527760
TI  - Advances in Optical Biopsy and Optical Mammography. Conference proceedings. New
      York City, New York, April 24-25, 1997.

PMID- 9527761
TI  - Aminoglycoside 6'-N-acetyltransferase variants of the Ib type with altered
      substrate profile in clinical isolates of Enterobacter cloacae and Citrobacter
      freundii.
AB  - Three clinical isolates, Enterobacter cloacae EC1562 and EC1563 and Citrobacter
      freundii CFr564, displayed an aminoglycoside resistance profile evocative of low
      level 6'-N acetyltransferase type II [AAC(6')-II] production, which conferred
      reduced susceptibility to gentamicin but not to amikacin or isepamicin.
      Aminoglycoside acetyltransferase assays suggested the synthesis in the three
      strains of an AAC(6') which acetylated amikacin practically as well as it
      acetylated gentamicin in vitro. Both compounds, however, as well as isepamicin,
      retained good bactericidal activity against the three strains. The aac genes were
      borne by conjugative plasmids (pLMM562 and pLMM564 of ca. 100 kb and pLMM563 of
      ca. 20 kb). By PCR mapping and nucleotide sequence analysis, an aac(6')-Ib gene
      was found in each strain upstream of an ant(3")-I gene in a sulI-type integron.
      The size of the AAC(6')-Ib variant encoded by pLMM562 and pLMM564, AAC(6')-Ib7,
      was deduced to be 184 (or 177) amino acids long, whereas in pLMM563 a 21-bp
      duplication allowing the recruitment of a start codon resulted in the translation
      of a variant, AAC(6')-Ib8, of 196 amino acids, in agreement with size estimates
      obtained by Western blot analysis. Both variants had at position 119 a serine
      instead of the leucine typical for the AAC(6')-Ib variants conferring resistance
      to amikacin. By using methods that predict the secondary structure, these two
      amino acids appear to condition an alpha-helical structure within a putative
      aminoglycoside binding domain of AAC(6')-Ib variants.

PMID- 9527762
TI  - The novel immunosuppressive agent mycophenolate mofetil markedly potentiates the
      antiherpesvirus activities of acyclovir, ganciclovir, and penciclovir in vitro
      and in vivo.
AB  - The immunosuppressive agent mycophenolate mofetil (MMF) has been approved for use
      in kidney transplant recipients and may thus be used concomitantly for the
      treatment of intercurrent herpesvirus infections with drugs such as acyclovir
      (ACV), ganciclovir (GCV), and penciclovir (PCV). We found that MMF and its parent
      compound mycophenolic acid (at concentrations that are attainable in plasma)
      strongly potentiate the antiherpesvirus (herpes simplex virus [HSV] type 1 [HSV
      1], HSV-2, thymidine kinase-deficient [TK-] HSV-1, both wild-type and TK-
      varicella-zoster virus, and human cytomegalovirus) activities of ACV, PCV, and
      GCV (up to 350-fold increases in their activities). The mechanism of potentiation
      was found to reside in the depletion of endogenous dGTP pools, which favored the
      inhibitory effect of the triphosphate of ACV, GCV, or PCV on the viral DNA
      polymerase. The combination of topically applied 5% MMF with 0.1% ACV strongly
      protected against HSV-1-induced cutaneous lesions in hairless mice, whereas
      therapy with either compound used singly had no protective effect. Interestingly,
      the combination of topically applied 5% MMF with 5% ACV was also highly effective
      in protecting against TK- HSV-2-induced cutaneous lesions (that were refractory
      to ACV treatment) in athymic nude mice. Topical therapy with MMF was very well
      tolerated, and no signs of irritation were observed. When given perorally at 200
      mg/kg of body weight/day, MMF potentiated to some extent the growth retardation
      induced by GCV in young NMRI mice. These observations may have clinical
      implications (i) for those transplant recipients who receive both MMF and either
      ACV, GCV, or PCV and (ii) for the treatment of ACV-resistant mucocutaneous HSV
      infections.

PMID- 9527763
TI  - Effect of fluconazole on indinavir pharmacokinetics in human immunodeficiency
      virus-infected patients.
AB  - To evaluate a potential pharmacokinetic interaction of coadministration of
      fluconazole, and indinavir, a human immunodeficiency virus (HIV) protease
      inhibitor, 13 patients were enrolled in a multiple-dose, three-period, placebo
      controlled, crossover study. Patients were randomly assigned to receive indinavir
      at 1,000 mg every 8 h for 7 1/3 days (with fluconazole placebo), fluconazole at
      400 mg once daily for 8 days (with indinavir placebo), and indinavir with
      fluconazole in combination. The pharmacokinetics of both drugs were measured on
      day 8 of each treatment period. The peak concentration in plasma (Cmax) and the
      time to reach Cmax were obtained by inspection, and the area under curve (AUC)
      was calculated for indinavir and fluconazole for each treatment period in which
      the respective drugs were administered. There was a marginally (P = 0.08)
      statistically significant decrease in the AUC from 0 to 8 h (AUC(0-8)) for
      indinavir when it was administered with fluconazole. However, the magnitudes of
      the decreases in Cmax and the concentration at 8 h postdosing (C8) were not as
      great as the decrease in AUC(0-8). Although the 90% confidence interval for the
      geometric mean ratio was within the hypothesized limits, the clinical
      significance is not clear. Indinavir coadministration with fluconazole had no
      statistically (P > 0.5) or clinically significant effect on the Cmax and C8 of
      indinavir. Fluconazole coadministration with indinavir had no statistically or
      clinically significant effect on the pharmacokinetics of fluconazole. One patient
      was discontinued because of mild to moderate abdominal pain and diarrhea while on
      indinavir and fluconazole in combination. No serious adverse experience according
      to the results of laboratory tests was noted. Total bilirubin levels in serum
      were mildly increased in most patients treated with indinavir. This was not
      clinically significant and was not affected by the coadministration of
      fluconazole. Although the values of the pharmacokinetic parameters for indinavir
      decrease in the presence of fluconazole, indinavir and fluconazole can be
      administered concomitantly to HIV-infected patients without adjustment of the
      dose of either drug, and both drugs are generally well tolerated.

PMID- 9527764
TI  - Chromogenic detection of aminoglycoside phosphotransferases.
AB  - A coupled chromogenic reaction (based on an agar overlay combining NADH, pyruvate
      kinase, lactate dehydrogenase, phosphoenolpyruvate, ATP, and kanamycin sulfate
      with thiazolyl blue-phenazine methosulfate for detection of NADH consumption) was
      optimized for the detection of aminoglycoside phosphotransferases (APHs). When
      used after analytical isoelectrofocusing of bacterial extracts from APH-producing
      strains, this method revealed one band in each of two strains with a genetically
      confirmed APH (3') I and two bands in another strain with both APH (3') I and APH
      (3') VI, whereas no bands were detected in susceptible control strains or in
      aminoglycoside-resistant microorganisms without APH genes.

PMID- 9527765
TI  - Pharmacodynamics of ampicillin-sulbactam in an in vitro infection model against
      Escherichia coli strains with various levels of resistance.
AB  - The activity of ampicillin-sulbactam against beta-lactamase-producing Escherichia
      coli has been questioned. Therefore, in this study, the killing activity of
      ampicillin-sulbactam was investigated in an in vitro infection model which
      simulates human pharmacokinetics. One ampicillin-sensitive strain (E. coli ATCC
      25922, ampicillin-sulbactam MIC = 4/2 microg/ml) and three ampicillin-resistant
      TEM-1-producing strains with various levels of ampicillin-sulbactam resistance
      (EC11, MIC = 4/2 microg/ml; TIM2, MIC = 12/6 microg/ml; and GB85, MIC > 128/64
      microg/ml) were studied. The E. coli strains were exposed to ampicillin-sulbactam
      at a starting inoculum of 6 to 7 log10 CFU/ml. Ampicillin-sulbactam was infused
      over 30 min to simulate doses of 3 and 1.5 g every 6 h for 24 h. The 3-g
      ampicillin-sulbactam dose was bactericidal against E. coli ATCC 25922, EC11, and
      TIM2. The 1.5-g dose displayed bactericidal activity against ATCC 25922 and EC11
      similar to that of the higher dose but failed to kill TIM2 due to inadequate time
      above the MIC and increased MICs over 24 h. GB85 was highly resistant and grew
      similarly to controls. Despite an MIC at 10(7) CFU/ml indicating resistance
      (20/10 microg/ml), TIM2 was killed by the 3-g dose of ampicillin-sulbactam.
      Current MIC breakpoints may not adequately portray the activity of ampicillin
      sulbactam, considering both the activity in in vitro infection models and
      clinical data.

PMID- 9527766
TI  - Detection of grlA and gyrA mutations in 344 Staphylococcus aureus strains.
AB  - Mutations in the grlA and gyrA genes of 344 clinical strains of Staphylococcus
      aureus isolated in 1994 in Japan were identified by combinations of single-strand
      conformation polymorphism analysis, restriction fragment length analysis, and
      direct sequencing to identify possible relationships to fluoroquinolone
      resistance. Five types of single-point mutations and four types of double
      mutations were observed in the grlA genes of 204 strains (59.3%). Four types of
      single-point mutations and four types of double mutations were found in the gyrA
      genes of 188 strains (54.7%). Among them, the grlA mutation of TCC-->TTC or TAC
      (Ser-80-->Phe or Tyr) and the gyrA mutation of TCA-->TTA (Ser-84-->Leu) were
      principal, being detected in 137 (39.8%) and 121 (35.9%) isolates, respectively.
      The grlA point mutations of CAT-->CAC (His-77 [silent]), TCA-->CCA (Ser-81-
      >Pro), and ATA-->ATT (Ile-100 [silent]) were novel, as was the GAC-->GGC (Asp-73-
      >Gly) change in gyrA. A total of 15 types of mutation combinations within both
      genes were related to ciprofloxacin resistance (MIC > or = 3.13 microg/ml) and
      were present in 193 mutants (56.1%). Strains containing mutations in both genes
      were highly resistant to ciprofloxacin (MIC at which 50% of the isolates are
      inhibited [MIC50] = 50 microg/ml). Those with the Ser80-->Phe or Tyr alteration
      in grlA but wild-type gyrA showed a lower level of ciprofloxacin resistance
      (MIC50 < or = 12.5 microg/ml). Levofloxacin was active against 68 of 193 isolates
      (35.2%) with mutations at codon 80 of grlA in the presence or absence of a
      concomitant mutation at codon 73, 84, or 88 in gyrA (MIC < or = 6.25 microg/ml).
      The new fluoroquinolone DU-6859a showed good activity with 186 of 193 isolates
      (96.4%) for which the MIC was < or = 6.25 microg/ml.

PMID- 9527768
TI  - Efficacy of trovafloxacin against experimental Staphylococcus aureus
      endocarditis.
AB  - Trovafloxacin is a new fluoronaphthyridone chemically and functionally related to
      members of the fluoroquinolone class of antimicrobial agents. The in vivo
      efficacy of the drug was compared with that of vancomycin by using the rabbit
      model of left-sided endocarditis. Rabbits infected with either a nafcillin
      susceptible or -resistant test strain were treated with trovafloxacin (13.3 mg/kg
      of body weight every 12 h) or vancomycin (25 mg/kg of body weight every 8 h) for
      4 days. In comparison with untreated controls, both antimicrobial agents
      effectively cleared bacteremia and significantly reduced bacterial counts in
      vegetations and tissues of animals infected with either test strain. No
      resistance to trovafloxacin emerged in test strains during therapy. We conclude
      that in this model trovafloxacin is as efficacious as vancomycin is and may serve
      as a viable alternative to vancomycin for use in humans with similar infections.

PMID- 9527767
TI  - Amino acid substitutions in the cytochrome P-450 lanosterol 14alpha-demethylase
      (CYP51A1) from azole-resistant Candida albicans clinical isolates contribute to
      resistance to azole antifungal agents.
AB  - The cytochrome P-450 lanosterol 14alpha-demethylase (CYP51A1) of yeasts is
      involved in an important step in the biosynthesis of ergosterol. Since CYP51A1 is
      the target of azole antifungal agents, this enzyme is potentially prone to
      alterations leading to resistance to these agents. Among them, a decrease in the
      affinity of CYP51A1 for these agents is possible. We showed in a group of Candida
      albicans isolates from AIDS patients that multidrug efflux transporters were
      playing an important role in the resistance of C. albicans to azole antifungal
      agents, but without excluding the involvement of other factors (D. Sanglard, K.
      Kuchler, F. Ischer, J.-L. Pagani, M. Monod, and J. Bille, Antimicrob. Agents
      Chemother. 39:2378-2386, 1995). We therefore analyzed in closer detail changes in
      the affinity of CYP51A1 for azole antifungal agents. A strategy consisting of
      functional expression in Saccharomyces cerevisiae of the C. albicans CYP51A1
      genes of sequential clinical isolates from patients was designed. This selection,
      which was coupled with a test of susceptibility to the azole derivatives
      fluconazole, ketoconazole, and itraconazole, enabled the detection of mutations
      in different cloned CYP51A1 genes, whose products are potentially affected in
      their affinity for azole derivatives. This selection enabled the detection of
      five different mutations in the cloned CYP51A1 genes which correlated with the
      occurrence of azole resistance in clinical C. albicans isolates. These mutations
      were as follows: replacement of the glycine at position 129 with alanine (G129A),
      Y132H, S405F, G464S, and R467K. While the S405F mutation was found as a single
      amino acid substitution in a CYP51A1 gene from an azole-resistant yeast, other
      mutations were found simultaneously in individual CYP51A1 genes, i.e., R467K with
      G464S, S405F with Y132H, G129A with G464S, and R467K with G464S and Y132H. Site
      directed mutagenesis of a wild-type CYP51A1 gene was performed to estimate the
      effect of each of these mutations on resistance to azole derivatives. Each single
      mutation, with the exception of G129A, had a measurable effect on the affinity of
      the target enzyme for specific azole derivatives. We speculate that these
      specific mutations could combine with the effect of multidrug efflux transporters
      in the clinical isolates and contribute to different patterns and stepwise
      increases in resistance to azole derivatives.

PMID- 9527769
TI  - A novel erythromycin resistance methylase gene (ermTR) in Streptococcus pyogenes.
AB  - Erythromycin resistance among streptococci is commonly due to target site
      modification by an rRNA-methylating enzyme, which results in coresistance to
      macrolide, lincosamide, and streptogramin B antibiotics (MLSB resistance). Genes
      belonging to the ermAM (ermB) gene class are the only erythromycin resistance
      methylase (erm) genes in Streptococcus pyogenes with MLSB resistance that have
      been sequenced so far. We identified a novel erm gene, designated ermTR, from an
      erythromycin-resistant clinical strain of S. pyogenes (strain A200) with an
      inducible type of MLSB resistance. The nucleotide sequence of ermTR is 82.5%
      identical to ermA, previously found, for example, in Staphylococcus aureus and
      coagulase-negative staphylococci. Our finding provides the first sequence of an
      erm gene other than ermAM that mediates MLSB resistance in S. pyogenes.

PMID- 9527770
TI  - Toxicological profile and pharmacokinetics of a unilamellar liposomal vesicle
      formulation of amphotericin B in rats.
AB  - AmBisome (ABLP) is a unilamellar liposomal preparation of amphotericin B that has
      demonstrated an improved safety profile compared to conventional amphotericin B.
      Single- and multiple-dose pharmacokinetics were determined by using
      noncompartmental methods for rats administered ABLP at 1, 3, 9, and 20 mg/kg/day.
      The toxicological profile was evaluated following 30 consecutive days of
      intravenous ABLP administration. Mean plasma amphotericin B concentrations
      reached 500 and 380 microg/ml (males and females, respectively) following 30 days
      of ABLP administration at 20 mg/kg. The overall apparent half-life was 11.2+/-4.5
      h (males) or 8.7+/-2.2 h (females), and the overall clearance (CL) was 9.4+/-5.5
      ml/h/kg (males) or 10.2+/-4.1 ml/h/kg (females). ABLP appears to undergo
      saturable disposition, resulting in a non-dose-proportional amphotericin B area
      under the curve and a lower CL at higher doses. Histopathological examination
      revealed dose-related transitional-cell hyperplasia in the transitional
      epithelium of the urinary tract (kidney, ureters, and urinary bladder) and
      moderate hepatocellular necrosis at the 20 mg/kg/day dose. Administration of ABLP
      in doses of up to 20 mg/kg/day resulted in 100-fold higher plasma amphotericin B
      concentrations, with significantly lower toxicity than that reported with
      conventional amphotericin B therapy.

PMID- 9527771
TI  - A rapid method for simultaneous detection of phenotypic resistance to inhibitors
      of protease and reverse transcriptase in recombinant human immunodeficiency virus
      type 1 isolates from patients treated with antiretroviral drugs.
AB  - Combination therapy with protease (PR) and reverse transcriptase (RT) inhibitors
      can efficiently suppress human immunodeficiency virus (HIV) replication, but the
      emergence of drug-resistant variants correlates strongly with therapeutic
      failure. Here we describe a new method for high-throughput analysis of clinical
      samples that permits the simultaneous detection of HIV type 1 (HIV-1) phenotypic
      resistance to both RT and PR inhibitors by means of recombinant virus assay
      technology. HIV-1 RNA is extracted from plasma samples, and a 2.2-kb fragment
      containing the entire HIV-1 PR- and RT-coding sequence is amplified by nested
      reverse transcription-PCR. The pool of PR-RT-coding sequences is then
      cotransfected into CD4+ T lymphocytes (MT4) with the pGEMT3deltaPRT plasmid from
      which most of the PR (codons 10 to 99) and RT (codons 1 to 482) sequences are
      deleted. Homologous recombination leads to the generation of chimeric viruses
      containing PR- and RT-coding sequences derived from HIV-1 RNA in plasma. The
      susceptibilities of the chimeric viruses to all currently available RT and/or PR
      inhibitors is determined by an MT4 cell-3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide-based cell viability assay in an automated system
      that allows high sample throughput. The profile of resistance to all RT and PR
      inhibitors is displayed graphically in a single PR-RT-Antivirogram. This assay
      system facilitates the rapid large-scale phenotypic resistance determinations for
      all RT and PR inhibitors in one standardized assay.

PMID- 9527772
TI  - Differential release of lipoteichoic and teichoic acids from Streptococcus
      pneumoniae as a result of exposure to beta-lactam antibiotics, rifamycins,
      trovafloxacin, and quinupristin-dalfopristin.
AB  - The release of lipoteichoic acid (LTA) and teichoic acid (TA) from a
      Streptococcus pneumoniae type 3 strain during exposure to ceftriaxone, meropenem,
      rifampin, rifabutin, quinupristin-dalfopristin, and trovafloxacin in tryptic soy
      broth was monitored by a newly developed enzyme-linked immunosorbent assay. At a
      concentration of 10 microg/ml, a rapid and intense release of LTA and TA occurred
      during exposure to ceftriaxone (3,248+/-1,688 ng/ml at 3 h and 3,827+/-2,133
      ng/ml at 12 h) and meropenem (2,464+/-1,081 ng/ml at 3 h and 2,900+/-1,364 ng/ml
      at 12 h). Three hours after exposure to rifampin, rifabutin, quinupristin
      dalfopristin, and trovafloxacin, mean LTA and TA concentrations of less than 460
      ng/ml were observed (for each group, P < 0.01 versus the concentrations after
      exposure to ceftriaxone). After 12 h of treatment, the LTA and TA concentrations
      were 463+/-126 ng/ml after exposure to rifampin, 669+/-303 ng/ml after exposure
      to rifabutin, and 1,236+/-772 ng/ml after exposure to quinupristin-dalfopristin
      (for each group, P < 0.05 versus the concentrations after exposure to
      ceftriaxone) and 1,745+/-1,185 ng/ml after exposure to trovafloxacin (P = 0.12
      versus the concentration after exposure to ceftriaxone). At 10 microg/ml,
      bactericidal antibacterial agents that do not primarily affect cell wall
      synthesis reduced the amount of LTA and TA released during their cidal action
      against S. pneumoniae in comparison with the amount released after exposure to
      beta-lactams. Larger quantities of LTA and TA were released after treatment with
      low concentrations (1x the MIC and 1x the minimum bactericidal concentration)
      than after no treatment for all antibacterial agents except the rifamycins. This
      does not support the concept of using a low first antibiotic dose to prevent the
      release of proinflammatory cell wall components.

PMID- 9527773
TI  - Evaluation of possible correlations between antifungal susceptibilities of
      filamentous fungi in vitro and antifungal treatment outcomes in animal infection
      models.
AB  - Nine isolates of filamentous fungi previously tested in 11 different laboratories
      for their susceptibilities to amphotericin B and itraconazole in vitro were
      injected intravenously into mice and guinea pigs, and responses to treatment with
      both agents were studied. The experiments were done in a single laboratory. Mean
      survival times, the percentages of animals surviving 12 days after infection, and
      culture results for samples of deep organs obtained postmortem were used as
      markers of antifungal efficacy. Because of variations in organism pathogenicity,
      interpretable test systems in vivo could not be established for Fusarium spp. in
      mice or guinea pigs or for Pseudallescheria boydii in mice, even with the use of
      immunosuppressive pretreatments. Among the infections that could be evaluated,
      some degree of response to the corresponding treatment in vivo was seen in
      animals infected with each of two Rhizopus arrhizus isolates susceptible to
      amphotericin B at < 0.5 microg/ml and Aspergillus spp. isolates susceptible to
      itraconazole at < 1.0 microg/ml. Conversely, no responses were apparent with
      infecting strains for which MICs were > or = 2 microg/ml (amphotericin B) or > or
      = 1 microg/ml (itraconazole). However, the limitations of the intravenous
      challenge systems studied mean that no firm conclusion relating MICs in vitro to
      the lowest effective doses in vivo could be drawn.

PMID- 9527774
TI  - Influence of renal failure on ciprofloxacin pharmacokinetics in rats.
AB  - Ciprofloxacin pharmacokinetics have been shown to be modified in patients with
      renal failure (e.g., the intestinal secretion of ciprofloxacin is increased).
      This study investigated the influence of renal failure on the pharmacokinetics of
      ciprofloxacin following oral and parenteral administration to rats of a dose of
      50 mg/kg of body weight. After parenteral administration, only renal clearance
      (CLR) was reduced in nephrectomized rats (5.3+/-1.4 versus 17.8+/-4.7 ml/min/kg,
      P < 0.01, nephrectomized versus control rats). However, nonrenal clearance was
      increased in nephrectomized rats (32+/-4 versus 15+/-5 ml/min/kg, P < 0.01,
      nephrectomized versus control rats), suggesting compensatory mechanisms for
      reduced renal function. After oral administration, apparent total clearance and
      CLR were reduced (P < 0.01) in nephrectomized rats (117+/-25 and 6.8+/-4.4
      ml/min/kg, respectively) compared with the values for control rats (185+/-9 and
      22.6+/-5.3 ml/min/kg, respectively) and the area under the concentration-time
      curve was higher (P < 0.01) for nephrectomized rats (436.3+/-90.5 mg. min/liter)
      than for control rats (271.3+/-14.3 mg.min/liter). Terminal elimination half
      lives in the two groups remained constant after oral and parenteral
      administration. These results suggest an increased bioavailability of
      ciprofloxacin in nephrectomized rats, which was confirmed by a nonlinear mixed
      effect model.

PMID- 9527775
TI  - Pharmacokinetics and absolute bioavailability of oral foscarnet in human
      immunodeficiency virus-seropositive patients.
AB  - The pharmacokinetics, absolute bioavailability, accumulation, and tolerability
      over 8 days of an oral formulation of foscarnet (90 mg/kg of body weight once
      daily [QD] [n = 6], 90 mg/kg twice daily [BID] [n = 6], and 180 mg/kg QD [n = 31)
      were investigated in 15 asymptomatic, human immunodeficiency virus-seropositive
      male patients free of active cytomegalovirus infection and with normal upper
      gastrointestinal function. Peak plasma drug concentrations were (mean +/-
      standard deviation) 46.4 +/- 10.8 microM (90 mg/kg QD), 45.7 +/- 6.9 microM (90
      mg/ kg BID), and 64.9 +/- 31.7 microM (180 mg/kg QD) on day 1 and rose to 86.2 +/
      35.8, 78.7 +/- 35.2, and 86.4 +/- 25.0 microM, respectively, on day 8. The mean
      peak concentration in plasma following the intravenous administration of
      foscarnet (90 mg/kg) was 887.3 +/- 102.7 microM (n = 13). The terminal half-life
      in plasma remained unchanged, averaging 5.5 +/- 2.2 h on day 1 (n = 15) and 6.6
      +/- 1.9 h on day 8 (n = 13), whereas it was 5.7 +/- 0.7 h following intravenous
      dosing. Oral bioavailabilities were 9.1% +/- 2.2% (90 mg/kg QD), 9.5% +/- 1.7%
      (90 mg/kg BID), and 7.6% +/- 3.7% (180 mg/kg QD); the accumulation ratios on the
      8th day of dosing were 2.1 +/- 1.1, 1.8 +/- 0.4, and 1.7 +/- 0.7, respectively.
      The overall 24-h urinary excretion of oral foscarnet averaged 7.8% +/- 2.6% (day
      1) and 13.4% +/- 6.0% (day 8), whereas it was 95.0% +/- 4.9% after intravenous
      dosing. The glomerular filtration rate and creatinine clearance remained
      constant, and the mean 24-h renal clearances of foscarnet for the entire study
      group were 96 +/- 18 ml/min (day 1), 88 +/- 13 ml/min (day 8), and 103 +/- 16
      ml/min after intravenous dosing. Adverse effects were largely confined to
      gastrointestinal disturbances, with all subjects experiencing diarrhea that was
      dose dependent in its severity. The results suggest that the formulation studied
      would require significant improvement with respect to tolerability and
      bioavailability to gain clinical acceptance.

PMID- 9527776
TI  - Evaluation of the safety and pharmacokinetic profile of a new, pasteurized, human
      tetanus immunoglobulin administered as sham, postexposure prophylaxis of tetanus.
AB  - In a monocentric, double-blind, randomized trial, we examined the safety and
      pharmacokinetic profile of a new, pasteurized, human tetanus immunoglobulin (P
      HTIG). As part of the purification process, P-HTIG has undergone a heat treatment
      step (10 h at 60 degrees C) and the removal of Merthiolate. Forty-eight adults
      with a history of tetanus vaccination were randomized into four groups (n = 12
      per group) to receive one of two different batches of this P-HTIG simultaneously
      with either tetanus-diphtheria (Td) vaccine (sham, postexposure prophylaxis of
      tetanus) or placebo. Local reactions at the injection site were followed for the
      first 3 days after injection, and systemic reactions were followed during the
      entire study period, i.e., up to 42 days posttreatment. Blood samples for tetanus
      antibody titer determination (enzyme-linked immunosorbent assay method) were
      drawn prior to treatment on day 0 and on days 1, 2, 3, 7, 14, 21, 28, 35, and 42.
      A normalization of tetanus antibody titers (subtraction of the day 0 value for
      each subject at each time period) was performed to assess the additive effect of
      P-HTIG on tetanus antibody titers. The pharmacokinetic parameters were determined
      by both a compartmental analysis (modelization) and a noncompartmental analysis.
      No severe adverse reactions were reported. The rate of local reactions at the P
      HTIG injection site was 27%. All local reactions were mild and resolved within 2
      days. In contrast, local reactions at the vaccine injection site were seen in 79%
      of the subjects. The rate of systemic reactions was similar in the P-HTIG plus Td
      vaccine group (33%) and in the P-HTIG plus placebo group (21%), and all these
      reactions were mild. In the P-HTIG plus placebo group, tetanus antibody titers
      rose to a maximum of 0.313+/-2.49 IU/ml after 4.4 days; in the P-HTIG plus Td
      vaccine group, a maximum concentration of 15.2+/-2.42 IU/ml was reached 19 days
      postinjection. In both groups, 100% of the patients had seroprotective levels of
      tetanus antibodies (> or = 0.01 IU/ml) 2 days following treatment. An anamnestic
      response to Td vaccine appeared 7 days postimmunization. In conclusion, P-HTIG
      has a good safety and pharmacokinetic profile. Our results confirm that
      immunoglobulin should be associated with vaccine in the treatment of tetanus
      prone wounds.

PMID- 9527777
TI  - Determination of the chromosomal relationship between mecA and gyrA in
      methicillin-resistant coagulase-negative staphylococci.
AB  - mecA, the gene that mediates methicillin resistance, and its accompanying mec
      locus DNA, insert near the gyrA gene in Staphylococcus aureus. To investigate
      whether there is a similar relationship between mecA and gyrA in coagulase
      negative staphylococci (CNS), mecA- and gyrA-specific DNA fragments were used to
      probe methicillin-resistant isolates of Staphylococcus epidermidis (MRSE) (n =
      11) and Staphylococcus haemolyticus (MRSH) (n = 11). The gyrA probe hybridized to
      the same SmaI DNA fragment as the mecA probe in all strains tested. However,
      since the size of the SmaI fragments containing mecA and gyrA varied from 73 to
      600 kb, the distance between the two genes was determined more precisely. Cloned
      mecA or gyrA fragments plus vector sequences each containing a SmaI site were
      introduced into the chromosome of three isolates each of MRSE and methicillin
      resistant S. aureus (MRSA), and the sizes of the generated SmaI fragments were
      determined by pulsed-field gel electrophoresis. The distance between gyrA and
      mecA was found to be between 38 and 42 kb in both MRSE and MRSA, and the two
      genes were in the same relative orientation in all strains. Restriction fragment
      length polymorphism (RFLP) patterns around the gyrA gene in CNS were identical,
      but species specific, for all 10 MRSE and 10 MRSH isolates examined. In contrast,
      8 of 11 methicillin-susceptible S. epidermidis isolates and 7 of 7 methicillin
      susceptible S. haemolyticus isolates had different gyrA RFLP patterns. These data
      show that mecA is site and orientation specific, relative to gyrA, in both MRSE
      and MRSA. In addition, the local environment around gyrA in methicillin-resistant
      CNS, in contrast to methicillin-susceptible isolates, is similar, suggesting
      clonality or the requirement for specific DNA sequences with which the mec
      complex must interact for chromosomal integration to occur.

PMID- 9527778
TI  - In vitro activity of a new oral triazole, BMS-207147 (ER-30346)
AB  - The antifungal activity of BMS-207147 (also known as ER-30346) was compared to
      those of itraconazole and fluconazole against 250 strains of fungi representing
      44 fungal species. MICs were determined by using the National Committee for
      Clinical Laboratory Standards (NCCLS)-recommended broth macrodilution method for
      yeasts, which was modified for filamentous fungi. BMS-207147 was about two- to
      fourfold more potent than itraconazole and about 40-fold more active than
      fluconazole against yeasts. With the NCCLS-recommended resistant MIC breakpoints
      of > or = 1 microg/ml for itraconazole and of > or = 64 microg/ml for fluconazole
      against Candida spp., itraconazole and fluconazole were inactive against strains
      of Candida krusei and Candida tropicalis. In contrast, all but 9 (all C.
      tropicalis) of the 116 Candida strains tested had BMS-207147 MICs of < 1
      microg/ml. The three triazoles were active against about half of the Candida
      glabrata strains and against all of the Cryptococcus neoformans strains tested.
      The three triazoles were fungistatic to most yeast species, except for BMS-207147
      and itraconazole, which were fungicidal to cryptococci. BMS-207147 and
      itraconazole were inhibitory to most aspergilli, and against half of the
      isolates, the activity was cidal. BMS-207147 and itraconazole were active, though
      not cidal, against most hyaline Hyphomycetes (with the exception of Fusarium spp.
      and Pseudallescheria boydii), dermatophytes, and the dematiaceous fungi and
      inactive against Sporothrix schenckii and zygomycetes. Fluconazole, on the other
      hand, was inactive against most filamentous fungi with the exception of
      dermatophytes other than Microsporum gypseum. Thus, the spectrum and potency of
      BMS-207147 indicate that it should be a candidate for clinical development.

PMID- 9527779
TI  - Antimicrobial susceptibility of Haemophilus influenzae in the respiratory tracts
      of patients with cystic fibrosis.
AB  - We analyzed the antimicrobial susceptibilities of Haemophilus influenzae isolates
      from 157 sputum specimens prospectively collected from 39 cystic fibrosis (CF)
      patients during a 2-year study. These isolates were characterized by random
      amplified polymorphic DNA analysis and major outer membrane protein (MOMP)
      analysis to identify H. influenzae strains and MOMP variants and to assess their
      persistence in the respiratory tract. Among the 247 H. influenzae isolates, 16
      (6.5%) produced beta-lactamase. The 231 beta-lactamase-negative isolates
      represented 85 H. influenzae strains, 61 MOMP variants derived from 27 of these
      strains, and 85 persistent isolates identical to strains or MOMP variants. All
      beta-lactamase-negative isolates were tested for susceptibility to ampicillin,
      amoxicillin-clavulanic acid, cefuroxime, cefotaxime, cefaclor, imipenem,
      tetracycline, and trimethoprim-sulfamethoxazole by disk diffusion testing. Eleven
      (13%) H. influenzae strains, 18 (30%) MOMP variants, and 30 (35%) persistent
      isolates were resistant to one or more of the antibiotics tested. Antimicrobial
      susceptibility was decreased among MOMP variants and persistent isolates compared
      to nonpersistent H. influenzae strains, and changes in susceptibility occurred
      irrespective of MOMP variation. We conclude that the decreased antimicrobial
      susceptibility of H. influenzae during persistence contributes to the poor
      eradication of H. influenzae from the respiratory tracts of CF patients.

PMID- 9527780
TI  - Stereoselective disposition of sulbenicillin in humans.
AB  - Stereoselective disposition of sulbenicillin (SBPC) epimers in healthy human
      volunteers was studied in order to clarify the differences in pharmacokinetic
      behavior between the epimers. Stereospecific high-performance liquid
      chromatography was used for the determination of SBPC epimers. Plasma protein
      binding was measured in vitro with an ultrafiltration method. The binding was
      stereoselective, with the unbound fraction (fu) of the R-epimer being
      approximately 1.3-fold greater than that of the S-epimer. SBPC was administered
      intravenously to human volunteers, and concentrations of SBPC in plasma and
      urinary excretion rates were measured. Renal clearance (CLR) for the unbound drug
      (approximately 400 ml/min) was greater than the glomerular filtration rate (GFR)
      (approximately 109 ml/min) for both epimers, suggesting that both epimers are
      secreted at the renal tubules. Renal tubular secretion appeared to be greater for
      the S-epimer. When probenecid was coadministered, the CLR values of both epimers
      were significantly reduced and were approximately equal to the GFR values. CLR
      was greater for the S-epimer (37.5 and 49.8 ml/min for R-SBPC and S-SBPC,
      respectively), which was simply due to the greater fu of the S-epimer in plasma.
      In contrast, total body clearance was greater for the R-epimer (67.8 and 56.3
      ml/min for R-SBPC and S-SBPC, respectively) because of the stereoselective
      degradation of the R-epimer in plasma. It was revealed that stereoselective
      degradation in the body had significant influence on the disposition of SBPC
      epimers.

PMID- 9527781
TI  - Single-dose pharmacokinetics of indinavir and the effect of food.
AB  - Indinavir sulfate is a human immunodeficiency virus type 1 (HIV-1) protease
      inhibitor indicated for treatment of HIV infection and AIDS in adults. The
      purpose of this report is to summarize single-dose studies which characterized
      the pharmacokinetics of the drug and the effect of food in healthy volunteers.
      Indinavir concentrations in plasma and urine were obtained by high-pressure
      liquid chromatography and UV detection assay methods. The results indicate that
      indinavir was rapidly absorbed in the fasting state, with the time to the maximum
      concentration in plasma occurring at approximately 0.8 h for all doses studied.
      Over the 40- to 1,000-mg dose range studied, concentrations in plasma and urinary
      excretion of unchanged drug increased greater than dose proportionally. The
      nonlinear pharmacokinetics were attributed to the dose-dependent oxidative
      metabolism of first-pass metabolism as well as to metabolism in the systemic
      circulation. Renal clearance slightly exceeded the glomerular filtration rate,
      suggesting a net tubular secretion component. At high concentrations in plasma,
      tubular secretion appeared to be lowered because there was a trend for a
      decreased renal clearance. Administration of 400 mg of indinavir sulfate
      following a high-fat breakfast resulted in a blunted and decreased absorption
      (areas under the concentration-time curves [AUCs], 6.86 microM.h in the fasted
      state versus 1.54 microM.h in the fed state; n = 10). However, two types of low
      fat meals were found to have no significant effect on the absorption of 800 mg of
      indinavir sulfate (AUCs, 23.15 microM.h in the fasted state versus 22.71 and
      21.36 microM.h, respectively, in the fed state; n = 11). Immediately following
      dosing, the concentrations of indinavir in urine often exceeded its intrinsic
      solubility. To reduce the risk of nephrolithiasis, it is recommended that
      indinavir sulfate be administered with water.

PMID- 9527782
TI  - Synthesis and evaluation of dinitroanilines for treatment of cryptosporidiosis.
AB  - The efficacy of a series of dinitroaniline herbicide derivatives for the
      treatment of Cryptosporidium parvum infections has been studied. The lead
      compounds oryzalin (compound 1) and trifluralin (compound 2) have low water
      solubility (<3 ppm) which was alleged to be a major contributor to their poor
      pharmacokinetic availability. Derivatives of compounds 1 and 2 were synthesized.
      In these derivatives the functionality at the C-1 amine position or the C-4
      position was substituted with groups with various hydrophilicities to determine
      if a direct relation existed between water solubility and overall activity. The
      chlorinated precursors of these derivatives were also examined and were found to
      be less active in the C. parvum assays, a result in direct contrast to earlier
      work with Leishmania. Enhanced water solubility alone did not overcome the drug
      availability problem; however, several candidates with similar activities but
      with toxicities lower than those of the lead compounds were produced.

PMID- 9527783
TI  - Green fluorescent protein reporter microplate assay for high-throughput screening
      of compounds against Mycobacterium tuberculosis.
AB  - An optimal assay for high-throughput screening for new antituberculosis agents
      would combine the microplate format and low cost of firefly luciferase reporter
      assays and redox dyes with the ease of kinetic monitoring inherent in the BACTEC
      system. The green fluorescent protein (GFP) of the jellyfish Aequorea victoria is
      a useful reporter molecule which requires neither substrates nor cofactors due to
      the intrinsically fluorescent nature of the protein. The gene encoding a red
      shifted, higher-intensity GFP variant was introduced by electroporation into
      Mycobacterium tuberculosis H37Ra and M. tuberculosis H37Rv on expression vector
      pFPV2. A microplate-based fluorescence assay (GFP microplate assay [GFPMA]) was
      developed and evaluated by determining the MICs of existing antimycobacterial
      agents. The MICs of isoniazid, rifampin, ethambutol, streptomycin, amikacin,
      ofloxacin, ethionamide, thiacetazone, and capreomycin, but not cycloserine,
      determined by GFPMA were within 1 log2 dilution of those determined with the
      BACTEC 460 system and were available in 7 days. Equivalent MICs of
      antituberculosis agents in the BACTEC 460 system for both the reporter and parent
      strains suggested that introduction of pFPV2 did not influence drug
      susceptibility, in general. GFPMA provides a unique tool with which the dynamic
      response of M. tuberculosis to the existing and potential antituberculosis agents
      can easily, rapidly, and inexpensively be monitored.

PMID- 9527784
TI  - A novel peptide-grafted liposomal delivery system targeted to macrophages.
AB  - The interaction of chemotactic peptide (e.g., fMet-Leu-Phe)-grafted liposomes
      with macrophages is noted to be rapid and specific. At a grafted peptide
      concentration of 100 nmol, internalization of the peptide-grafted liposomes by
      the macrophages is found to reach equilibrium in 30 min. The peptide alone and
      the peptide-grafted empty liposomes are found to show moderate antileishmanial
      activity in vitro. Primaquine, which is known to generate O2- in phagocytic
      cells, showed leishmanicidal properties when it was tested in vitro against
      parasite-infected macrophages over a certain range of concentrations. It showed
      much better efficacy against experimental leishmaniasis when it was used in the
      fMet-Leu-Phe-grafted liposomal form in comparison with its efficacy when it was
      either in the free form or encapsulated in ungrafted liposomes. The conventional
      toxicity parameters (e.g., blood pathology and tissue histology-specific enzyme
      levels related to normal liver function) are found to be very close to normal
      when fMet-Leu-Phe-grafted liposomal primaquine is used. The biodegradabilities of
      both the drug and the delivery systems are also found to be very satisfactory.
      Thus, this delivery system may have possible applications for the treatment of
      leishmaniasis as well as other macrophage-associated disorders.

PMID- 9527786
TI  - Mathematical modeling of the interrelationship of CD4 lymphocyte count and viral
      load changes induced by the protease inhibitor indinavir.
AB  - While CD4 cell counts are widely used to predict disease progression in human
      immunodeficiency virus (HIV)-infected patients, they are poorly explanatory of
      the progression to AIDS or death after the introduction of chemotherapy. Changes
      in HIV load (as measured by RNA PCR) have been shown to be a much better
      predictor of the risk of disease progression. Since the interrelationship of
      these markers is of great clinical interest, we modeled the time-averaged return
      of CD4 cell count and change in viral load subsequent to therapy with the HIV
      protease inhibitor indinavir. We found that CD4 cell return was significantly
      related to both the baseline CD4 count (r2 = 0.86, P < 0.001) and the decline in
      HIV RNA PCR-determined viral load (also referred to in this work as the HIV RNA
      PCR decline) (r2 = 0.60, P < 0.01). Simultaneously modeling both influences in a
      linked nonlinear model (r2 = 0.93, P < 0.001) demonstrated that (i) the starting
      number of CD4 cells accounted for the majority of the change in CD4 cell return
      and (ii) the return of CD4 cells attributable to viral load decrease was 50% of
      maximal with only a decrease of approximately 0.2 log of HIV RNA as modeled from
      the first 12 weeks of therapy. Much greater viral inhibition beyond that
      necessary for maximal CD4 cell return is possible. Given that HIV RNA PCR decline
      is more strongly linked to ultimate clinical course in HIV disease, our findings
      indicate that CD4 return is potentially misleading as an indicator of antiviral
      effect, since it is determined more by the starting CD4 value than by viral load
      decline and since near-maximal changes occur with minimal antiviral effect.

PMID- 9527785
TI  - Mechanism of amphotericin B resistance in Leishmania donovani promastigotes.
AB  - Amphotericin B (AmB)-resistant Leishmania donovani promastigotes were selected by
      increasing drug pressure, and their biological features were compared with those
      of the wild-type parent strain. The 50% inhibitory concentration for resistant
      cells was 20 times higher than that for the wild-type. Resistance was stable
      after more than 40 passages in drug-free medium, and resistant promastigotes were
      infective to macrophages in vitro but lost their virulence in vivo. They had 2.5
      times longer generation time, decreased AmB uptake, and increased AmB efflux in
      comparison to the wild type. Fluorescence measurement with a specific plasma
      membrane probe, 1-[4-(trimethylammonio)-1,6-diphenylhexa]-1,3,5-triene, showed
      increased membrane fluidity in drug-resistant promastigotes. Analysis of lipid
      composition showed that in resistant cells saturated fatty acids were prevalent,
      with stearic acid as the major fatty acid, and the major sterol was an ergosterol
      precursor, the cholesta-5, 7, 24-trien-3beta-ol and not ergosterol as in the AmB
      sensitive strain.

PMID- 9527788
TI  - Inhibitory effect of 2'-fluoro-5-methyl-beta-L-arabinofuranosyl-uracil on duck
      hepatitis B virus replication.
AB  - The antiviral activity of 2'-fluoro-5-methyl-beta-L-arabinofuranosyluracil (L
      FMAU), a novel L-nucleoside analog of thymidine known to be an inhibitor of
      hepatitis B virus (HBV) replication in hepatoma cells (2.2.1.5 cell line), was
      evaluated in the duck HBV (DHBV) model. Short-term oral administration (5 days)
      of L-FMAU (40 mg/kg of body weight/day) to experimentally infected ducklings
      induced a significant decrease in the level of viremia. This antiviral effect was
      sustained in animals when therapy was prolonged for 8 days. The histological
      study showed no evidence of liver toxicity in the L-FMAU-treated group. By
      contrast, microvesicular steatosis was found in the livers of dideoxycytidine
      treated animals. L-FMAU administration in primary duck hepatocyte cultures
      infected with DHBV induced a dose-dependent inhibition of both virion release in
      culture supernatants and intracellular viral DNA synthesis, without clearance of
      viral covalently closed circular DNA. By using a cell-free system for the
      expression of an enzymatically active DHBV reverse transcriptase, it was shown
      that L-FMAU triphosphate exhibits an inhibitory effect on the incorporation of
      dAMP in the viral DNA primer. Thus, our data demonstrate that L-FMAU inhibits
      DHBV replication in vitro and in vivo. Long-term administration of L-FMAU for the
      eradication of viral infection in animal models of HBV infection should be
      evaluated.

PMID- 9527789
TI  - Comparison of pharmacodynamics of azithromycin and erythromycin in vitro and in
      vivo.
AB  - In this study, we determined the efficacy of various dosing regimens for
      erythromycin and azithromycin against four pneumococci with different
      susceptibilities to penicillin in an in vitro pharmacokinetic model and in a
      mouse peritonitis model. The MIC was 0.03 microg/ml, and the 50% effective doses
      (determined after one dose) of both drugs were comparable for the four
      pneumococcal strains and were in the range of 1.83 to 6.22 mg/kg. Dosing
      experiments with mice, using regimens for azithromycin of one to eight doses/6 h,
      showed the one-dose regimen to give the best result; of the pharmacodynamic
      parameters tested (the maximum drug concentration in serum [Cmax], the times that
      the drug concentration in serum remained above the MIC and above the
      concentration required for maximum killing, and the area under the concentration
      time curve), Cmax was the best predictor of outcome. The bacterial counts in
      mouse blood or peritoneal fluid during the first 24 h after challenge were not
      correlated to survival of the mice. The serum concentration profiles obtained
      with mice for the different dosing regimens were simulated in the in vitro
      pharmacokinetic model. Here as well, the one-dose regimen of azithromycin showed
      the best result. However, the killing curves in vivo in mouse blood and
      peritoneal fluid and in the vitro pharmacokinetic model were not similar. The in
      vitro killing curves showed a decrease of 2 log10 within 2 and 3 h for
      azithromycin and erythromycin, respectively whereas the in vivo killing curves
      showed a bacteriostatic effect for both drugs. It is concluded that the results
      in terms of predictive pharmacodynamic parameters are comparable for the in vitro
      and in vivo models and that high initial concentrations of azithromycin favor a
      good outcome.

PMID- 9527787
TI  - Doxycycline hyclate treatment of experimental canine ehrlichiosis followed by
      challenge inoculation with two Ehrlichia canis strains.
AB  - Dogs were experimentally inoculated with Ehrlichia canis Florida to assess the
      efficacy of doxycycline hyclate for the treatment of acute ehrlichiosis.
      Treatment with doxycycline eliminated infection in eight of eight dogs. Untreated
      infected control dogs appeared to eliminate the infection or, alternatively,
      suppress the degree of ehrlichiemia to a level not detectable by tissue culture
      isolation or PCR or by transfusion of blood into recipient dogs. Prior infection
      did not infer protection against homologous (strain Florida) or heterologous
      (strain NCSU Jake) strains of E. canis. We conclude that doxycycline hyclate is
      an effective treatment for acute E. canis infection; however, these results may
      not be applicable to chronic infections in nature. Spontaneous resolution of
      infection, induced by the dog's innate immune response, provides evidence that an
      E. canis vaccine, once developed, might potentially confer protective immunity
      against the organism.

PMID- 9527790
TI  - TXU (anti-CD7)-pokeweed antiviral protein as a potent inhibitor of human
      immunodeficiency virus.
AB  - We have evaluated the clinical potential of TXU (anti-CD7)-pokeweed antiviral
      protein (PAP) immunoconjugate (TXU-PAP) as a new biotherapeutic anti-human
      immunodeficiency virus (anti-HIV) agent by evaluating its anti-HIV type 1 (anti
      HIV-1) activity in vitro, as well as in a surrogate human peripheral blood
      lymphocyte-severe combined immunodeficient (Hu-PBL-SCID) mouse model of human
      AIDS. The present report documents in a side-by-side comparison the superior in
      vitro anti-HIV-1 activity of TXU-PAP compared to the activities of zidovudine,
      2',3'-didehydro-2',3'-dideoxythymidine, unconjugated PAP, and B53-PAP, an anti
      CD4-PAP immunoconjugate. Notably, TXU-PAP elicited potent anti-HIV activity in
      the Hu-PBL-SCID mouse model of human AIDS without any side effects and at doses
      that were very well tolerated by cynomolgus monkeys. Furthermore, plasma samples
      from TXU-PAP-treated cynomolgus monkeys showed potent anti-HIV-1 activity in
      vitro.

PMID- 9527791
TI  - Cellular accumulation, localization, and activity of a synthetic cyclopeptamine
      in fungi.
AB  - A novel synthetic cyclopeptamine, A172013, rapidly accumulated by passive
      diffusion into Candida albicans CCH442. Drug influx could not be totally
      facilitated by the membrane-bound target, beta-(1,3)-glucan synthase, since
      accumulation was unsaturable at drug concentrations up to 10 microg/ml (about 1.6
      x 10(-7) molecules/cell), or 25x MIC. About 55 and 23% of the cell-incorporated
      drug was associated with the cell wall and protoplasts, respectively. Isolated
      microsomes contained 95% of the protoplast-associated drug, which was fully
      active against glucan synthesis in vitro. Drug (0.1 microg/ml) accumulation was
      rapid and complete after 5 min in several fungi tested, including a
      lipopeptide/cyclopeptamine-resistant strain of C. albicans (LP3-1). The compound
      penetrated to comparable levels in both yeast and hyphal forms of C. albicans,
      and accumulation in Aspergillus niger was 20% that in C. albicans. These data
      indicated that drug-cell interactions were driven by the amphiphilic nature of
      the compound and that the cell wall served as a major drug reservoir.

PMID- 9527792
TI  - Intrinsic resistance to inhibitors of fatty acid biosynthesis in Pseudomonas
      aeruginosa is due to efflux: application of a novel technique for generation of
      unmarked chromosomal mutations for the study of efflux systems.
AB  - Many strains of Pseudomonas aeruginosa are resistant to the antibiotics cerulenin
      and thiolactomycin, potent inhibitors of bacterial fatty acid biosynthesis. A
      novel yeast Flp recombinase-based technique was used to isolate an unmarked mexAB
      oprM deletion encoding an efflux system mediating resistance to multiple
      antibiotics in P. aeruginosa. The experiments showed that the MexAB-OprM system
      is responsible for the intrinsic resistance of this bacterium to cerulenin and
      thiolactomycin. Whereas thiolactomycin was not a substrate of the MexCD-OprJ pump
      expressed in a delta(mexAB-oprM) nfxB mutant, cerulenin was efficiently effluxed
      by the MexCD-OprJ system. It was also found that the MexAB-OprM system is capable
      of efflux of irgasan, a broad-spectrum antimicrobial compound used in media
      selective for Pseudomonas.

PMID- 9527793
TI  - Beta-lactamase inhibitors are substrates for the multidrug efflux pumps of
      Pseudomonas aeruginosa.
AB  - The MexAB-OprM multidrug efflux system exports a number of antimicrobial
      compounds, including beta-lactams. In an attempt to define more fully the range
      of antimicrobial compounds exported by this system, and, in particular, to
      determine whether beta-lactamase inhibitors were also accommodated by the MexAB
      OprM pump, the influence of pump status (its presence or absence) on the
      intrinsic antibacterial activities of these compounds and on their abilities to
      enhance beta-lactam susceptibility in intact cells was assessed. MIC
      determinations clearly demonstrated that all three compounds tested, clavulanate,
      cloxacillin, and BRL42715, were accommodated by the pump. Moreover, by using beta
      lactams which were readily hydrolyzed by the Pseudomonas aeruginosa class C
      chromosomal beta-lactamase, it was demonstrated that elimination of the mexAB
      oprM-encoded efflux system greatly enhanced the abilities of cloxacillin and
      BRL42715 (but not clavulanate) to increase beta-lactam susceptibility. With beta
      lactams which were poorly hydrolyzed, however, the inhibitors failed to enhance
      beta-lactam susceptibility in MexAB-OprM+ strains, although BRL42715 did enhance
      beta-lactam susceptibility in MexAB-OprM- strains, suggesting that even with
      poorly hydrolyzed beta-lactams this inhibitor was effective when it was not
      subjected to efflux. MexEF-OprN-overexpressing strains, but not MexCD-OprJ
      overexpressing strains, also facilitated resistance to beta-lactamase inhibitors,
      indicating that these compounds are also substrates for the MexEF-OprN pump.
      These data indicate that an ability to inactivate MexAB-OprM (and like efflux
      systems in other bacteria) will markedly enhance the efficacies of beta-lactam
      beta-lactamase inhibitor combinations in treating bacterial infections.

PMID- 9527794
TI  - Repeated-dose pharmacokinetics of an oral solution of itraconazole in infants and
      children.
AB  - The safety, tolerability, and pharmacokinetics of an oral solution of
      itraconazole and its active metabolite hydroxyitraconazole were investigated in
      an open multicenter study of 26 infants and children aged 6 months to 12 years
      with documented mucosal fungal infections or at risk for the development of
      invasive fungal disease. The most frequent underlying illness was acute
      lymphoblastic leukemia, except in the patients aged 6 months to 2 years, of whom
      six were liver transplant recipients. The patients were treated with itraconazole
      at a dosage of 5 mg/kg of body weight once daily for 2 weeks. Blood samples were
      taken after the first dose, during treatment, and up to 8 days after the last
      itraconazole dose. On day 1, the mean peak concentrations in plasma after the
      first and last doses (Cmax) and areas under the concentration-time curve from 0
      to 24 h (AUC0-24) for itraconazole and hydroxyitraconazole were lower in the
      children aged 6 months to 2 years than in children aged 2 to 12 years but were
      comparable on day 14. The mean AUC0-24-based accumulation factors of itraconazole
      and hydroxyitraconazole from day 1 to 14 ranged from 3.3 to 8.6 and 2.3 to 11.4,
      respectively. After 14 days of treatment, Cmax, AUC0-24, and the half-life,
      respectively, were (mean +/- standard deviation) 571+/-416 ng/ml, 6,930+/-5,830
      ng.h/ml, and 47+/-55 h in the children aged 6 months to 2 years; 534+/-431 ng/ml,
      7,330+/-5,420 ng.h/ml, and 30.6+/-25.3 h in the children aged 2 to 5 years; and
      631+/-358 ng/ml, 8,770+/-5,050 ng.h/ml, and 28.3+/-9.6 h in the children aged 5
      to 12 years. There was a tendency to have more frequent low minimum
      concentrations of the drugs in plasma for both itraconazole and
      hydroxyitraconazole for the children aged 6 months to 2 years. The oral
      bioavailability of the solubilizer hydroxypropyl-beta-cyclodextrin was less than
      1% in the majority of the patients. In conclusion, an itraconazole oral solution
      given at 5 mg/kg/day provides potentially therapeutic concentrations in plasma,
      which are, however, substantially lower than those attained in adult cancer
      patients, and is well tolerated and safe in infants and children.

PMID- 9527795
TI  - Zalcitabine population pharmacokinetics: application of radioimmunoassay.
AB  - Zalcitabine population pharmacokinetics were evaluated in 44 human
      immunodeficiency virus-infected patients (39 males and 5 females) in our
      immunodeficiency clinic. Eighty-one blood samples were collected during routine
      clinic visits for the measurement of plasma zalcitabine concentrations by
      radioimmunoassay (1.84+/-1.24 samples/patient; range, 1 to 6 samples/patient).
      These data, along with dosing information, age (38.6+/-7.13 years), sex, weight
      (79.1+/-15.0 kg), and estimated creatinine clearance (89.1+/-21.5 ml/min), were
      entered into NONMEM to obtain population estimates for zalcitabine
      pharmacokinetic parameters. The standard curve of the radioimmunoassay ranged
      from 0.5 to 50.0 ng/ml. The observed concentrations of zalcitabine in plasma
      ranged from 2.01 to 8.57 ng/ml following the administration of doses of either
      0.375 or 0.75 mg. A one-compartment model best fit the data. The addition of
      patient covariates did not improve the basic fit of the model to the data. Oral
      clearance was determined to be 14.8 liters/h (0.19 liter/h/kg; coefficient of
      variation [CV] = 23.8%), while the volume of distribution was estimated to be
      87.6 liters (1.18 liters/kg; CV = 54.0%). We were also able to obtain individual
      estimates of oral clearance (range, 8.05 to 19.8 liters/h; 0.11 to 0.30
      liter/h/kg) and volume of distribution (range, 49.2 to 161 liters; 0.43 to 1.92
      liters/kg) of zalcitabine in these patients with the POSTHOC option in NONMEM.
      Our value for oral clearance agrees well with other estimates of oral clearance
      from traditional pharmacokinetic studies of zalcitabine and suggests that
      population methods may be a reasonable alternative to these traditional
      approaches for obtaining information on the disposition of zalcitabine.

PMID- 9527796
TI  - Postanitbiotic and sub-MIC effects of azithromycin and isepamicin against
      Staphylococcus aureus and Escherichia coli.
AB  - Investigations of pharmacodynamic parameters (postantibiotic effect [PAE], sub
      MIC effects [SMEs], etc.) have been progressively employed for the design of
      dosing schedules of antimicrobial agents. However, there are fewer in vivo than
      in vitro data, probably because of the simplicity of the in vitro procedures. In
      this study, we have investigated the in vitro PAE, SME, and previously treated
      (postantibiotic [PA]) SME (1/2 MIC, 1/4 MIC and 1/8 MIC) of azithromycin and
      isepamicin against standard strains of Staphylococcus aureus and Escherichia coli
      by using centrifugation to remove the antibiotics. In addition, the in vivo PAE
      and SME have been studied with the thigh infection model in neutropenic mice.
      Finally, in vivo killing curves with two dosing schedules were determined to
      examine whether the PAE can cover the time that antimicrobial agents are below
      the MIC. The two antimicrobial agents induced moderate-to-high in vitro PAEs,
      SMEs, and PA SMEs against S. aureus (>8 h) and E. coli (3.38 to >7.64 h). The in
      vivo PAEs were also high (from 3.0 to 3.6 h), despite the fact that isepamicin
      had lower times above the MIC in serum. Only azithromycin showed a high in vivo
      SME against the two strains (1.22 and 1.75 h), which indicated that the in vivo
      PAEs were possibly overestimated. In the killing kinetics, no great differences
      (<0.5 log10) were observed between the schedule that took the PAE into account
      and the continuous administration of doses. These results are comparable with
      those of other authors and suggest that these antimicrobial agents could be
      administered at longer intervals without losing effectiveness.

PMID- 9527797
TI  - In vitro activities of Y-688, a new 7-substituted fluoroquinolone, against
      anaerobic bacteria.
AB  - The in vitro activities of Y-688, a new 7-substituted fluoroquinolone derivative,
      against 317 nonduplicate anaerobic isolates were determined. Eighty-five percent
      of the Bacteroides fragilis group (n = 89) were inhibited by < or = 2 mg of Y-688
      per liter, while 78, 100, 89, and 98% of gram-negative bacilli (n = 135), gram
      positive cocci (n = 59), and non-spore-forming (n = 58) and spore-forming (n =
      51) gram-positive bacilli, respectively, were inhibited by < or = 1 mg of Y-688
      per liter.

PMID- 9527798
TI  - Concentrations of pefloxacin in plasma and tissue after administration as
      surgical prophylaxis.
AB  - Plasma and epiploic-fat drug concentrations determined by high-performance liquid
      chromatography and fat penetration of pefloxacin and its metabolite (norfloxacin)
      given for antimicrobial prophylaxis were studied in patients scheduled for
      colorectal surgery. Concentrations of pefloxacin in plasma decreased about 40%
      from the beginning of the operation to closure of the peritoneum, and
      corresponding levels in epiploic fat stayed stable. The plasma and tissue
      norfloxacin concentrations were very low. Concentrations of pefloxacin in tissue
      were greater than MIC at which 90% of isolates are inhibited for sensitive
      bacteria (members of the family Enterobacteriaceae). The penetration of
      pefloxacin into epiploic fat was about 32%.

PMID- 9527799
TI  - Pharmacokinetics and inflammatory fluid penetration of clinafloxacin.
AB  - A single 200-mg dose of clinafloxacin was given orally to each of nine healthy
      male volunteers, and the concentrations of the drug were measured in plasma,
      cantharidin-induced inflammatory fluid, and urine over the following 24 h (48 h
      in the case of urine). The mean maximum concentration in plasma was 1.34
      microg/ml at a mean time of 1.8 h postdose. The mean maximum concentration in the
      inflammatory fluid was 1.3 microg/ml at 3.8 h postdose. The mean elimination half
      life of clinafloxacin in plasma was 5.65 h. The overall penetration into the
      inflammatory fluid was 93.1%, as assessed by determining the ratio of area under
      the concentration-time curves. Recovery of clinafloxacin in urine was 58.8% by 24
      h and 71.8% by 48 h postdose.

PMID- 9527800
TI  - Antibiotic susceptibility of enterohemorrhagic Escherichia coli O157:H7 isolated
      from an outbreak in Japan in 1996.
AB  - The antibiotic susceptibilities of 43 strains of Escherichia coli O157:H7
      identified in the summer of 1996 in Japan were investigated. Growth of 90% of
      O157 strains was inhibited at a concentration of < or = 0.5 micro/ml by several
      agents including fosfomycin with glucose-6-phosphate.

PMID- 9527801
TI  - Alterations in the GyrA subunit of DNA gyrase and the ParC subunit of DNA
      topoisomerase IV associated with quinolone resistance in Enterococcus faecalis.
AB  - The gyrA and parC genes of 31 clinical isolates of Enterococcus faecalis,
      including fluoroquinolone-resistant isolates, were partially sequenced and
      analyzed for target alterations. Topoisomerase IV may be a primary target in E.
      faecalis, but high-level fluoroquinolone resistance was associated with
      simultaneous alterations in both GyrA and ParC.

PMID- 9527802
TI  - Nucleotide and amino acid sequences of the metallo-beta-lactamase, ImiS, from
      Aeromonas veronii bv. sobria.
AB  - The Aeromonas veronii bv. sobria metallo-beta-lactamase gene, imiS, was cloned.
      The imiS open reading frame extends for 762 bp and encodes a protein of 254 amino
      acids with a secreted modified protein of 227 amino acids and a predicted pI of
      8.1. To confirm the predicted sequence, purified ImiS was digested and the
      resulting peptides were identified, yielding an identical sequence for ImiS, with
      98% identity to CphA. Both possessed the putative active-site sequence Asn-Tyr
      His-Thr-Asp at positions 88 to 92, which is unique to the Aeromonas metallo-beta
      lactamases.

PMID- 9527803
TI  - Antimicrobial resistance in Shigella flexneri and Shigella sonnei in Hong Kong,
      1986 to 1995.
AB  - Three hundred and thirty-three Shigella isolates obtained in 1986 to 1995 were
      tested for their susceptibilities to 19 antimicrobial agents. Nalidixic acid
      resistance had emerged in 59.6% of Shigella flexneri isolates during 1994 to
      1995, with all tested resistant isolates having the mutation in gyrA encoding the
      Ser-83 alteration. Multiresistance (resistance to four or more agents) was more
      common in S. flexneri than in Shigella sonnei.

PMID- 9527804
TI  - The Cys607-->Tyr change in the UL97 phosphotransferase confers ganciclovir
      resistance to two human cytomegalovirus strains recovered from two
      immunocompromised patients.
AB  - Two ganciclovir (GCV)-resistant human cytomegalovirus (HCMV) strains recovered
      from an AIDS patient (strain VR4990) and a heart transplant recipient (strain
      VR5474) showed a Cys607-->Tyr change in the UL97-encoded phosphotransferase. No
      amino acid substitutions were observed in the viral DNA polymerase. Marker
      transfer experiments showed marked reduction in GCV phosphorylation and drug
      susceptibility of the recombinant HCMV strain VR4990rec2-1-1. These results
      further extend the region of the carboxy-terminal domain of the UL97
      phosphotransferase involved in GCV substrate recognition.

PMID- 9527806
TI  - Effects of aluminum hydroxide and famotidine on bioavailability of tosufloxacin
      in healthy volunteers.
AB  - This study was designed to determine the influence of aluminum hydroxide and
      famotidine on the bioavailability of tosufloxacin. Coadministration of aluminum
      hydroxide reduced the bioavailability of tosufloxacin by 31.6% (P < 0.05).
      Famotidine did not alter tosufloxacin absorption. To avoid potential treatment
      failures, the concurrent use of tosufloxacin and aluminum hydroxide should be
      avoided altogether.

PMID- 9527805
TI  - A mutation at position 190 of human immunodeficiency virus type 1 reverse
      transcriptase interacts with mutations at positions 74 and 75 via the template
      primer.
AB  - We have analyzed amino acid substitutions at position G190 in the reverse
      transcriptase (RT) of human immunodeficiency virus type 1 (HIV-1). The mutation
      G190E, which is responsible for resistance to certain nonnucleoside inhibitors,
      results in RT that has significantly less polymerase activity and that is less
      processive than wild-type RT. Its kinetic profile with respect to dGTP and
      poly(rC).oligo(dG) is significantly altered compared to that of wild-type RT. The
      combination of either of the mutations L74V or V75I with the G190E mutation
      appears to be compensatory and mitigates many of the deleterious effects of the
      G190E mutation.

PMID- 9527807
TI  - Effects of probenecid and cimetidine on renal disposition of ofloxacin in rats.
AB  - The renal handling of ofloxacin in rats which were given ofloxacin either alone
      or in combination with probenecid or cimetidine was studied. In the presence of
      cimetidine or probenecid, ofloxacin's total and renal clearances were reduced and
      its half-life was prolonged. This suggests that ofloxacin is secreted by both the
      anionic and cationic transport systems.

PMID- 9527808
TI  - Rationale for and efficacy of prolonged-interval treatment using liposome
      encapsulated amikacin in experimental Mycobacterium avium infection.
AB  - The potential of liposome-encapsulated antibiotics for prolonging drug
      application intervals was investigated by using a murine model of chronic lethal
      Mycobacterium avium infection. Liposomal encapsulation of amikacin, but not of
      ciprofloxacin, resulted in high and sustained drug levels in infected tissues,
      exceeding the minimal inhibitory concentration for M. avium for at least 28 days.
      As a consequence, once-weekly and even once-monthly treatments with liposomal
      amikacin significantly reduced bacterial replication in infected tissues and
      extended the survival time of infected mice.

PMID- 9527809
TI  - In vitro antimycobacterial activity of 5-chloropyrazinamide.
AB  - 5-Chloropyrazinamide and 5-chloropyrazinoic acid were evaluated for in vitro
      activity against Mycobacterium tuberculosis, Mycobacterium bovis, and several
      nontuberculous mycobacteria by a broth dilution method. 5-Chloropyrazinamide was
      more active than pyrazinamide against all organisms tested. It is likely that
      this agent has a different mechanism of action than pyrazinamide.

PMID- 9527811
TI  - Critical importance of in vivo amoxicillin and cefotaxime concentrations for
      synergy in treatment of experimental Enterococcus faecalis endocarditis.
AB  - The synergy between amoxicillin and cefotaxime against two strains of
      Enterococcus faecalis (JH2-2 and 6370) in vitro and in rabbit endocarditis was
      investigated. In vitro synergy was obtained only when amoxicillin concentrations
      were below the MBC and when cefotaxime concentrations were above 1 microg/ml. No
      synergy was observed in vivo, because of the short period of time during which
      these pharmacologic requirements were achieved.

PMID- 9527810
TI  - Characterization of FOX-3, an AmpC-type plasmid-mediated beta-lactamase from an
      Italian isolate of Klebsiella oxytoca.
AB  - Klebsiella oxytoca 1731, which showed a wide spectrum of resistance to beta
      lactams, including cefoxitin, was isolated in 1994 from a patient in Genoa,
      Italy. This strain contained a plasmid-mediated AmpC beta-lactamase with a pI of
      7.25. Sequencing of the corresponding DNA of K. oxytoca 1731 revealed 96 and 97%
      identities of the deduced amino acid sequence with FOX-1 and FOX-2, respectively.

PMID- 9527812
TI  - In vitro comparative efficacy of voriconazole and itraconazole against
      fluconazole-susceptible and -resistant Cryptococcus neoformans isolates.
AB  - In vitro susceptibility testing for 50 clinical isolates of fluconazole
      susceptible or -resistant Cryptococcus neoformans was performed with itraconazole
      and voriconazole. Voriconazole was more potent than itraconazole for fluconazole
      susceptible isolates and as potent as itraconazole for fluconazole-susceptible
      dose-dependent isolates and for fluconazole-resistant isolates. For fluconazole
      resistant isolates, the voriconazole and itraconazole MICs ranged from 1 to 2
      microg/ml.

PMID- 9527813
TI  - Effect of cholera toxin on intestinal elimination of ciprofloxacin in rabbits.
AB  - The transepithelial intestinal elimination of ciprofloxacin (CPX) was studied in
      cholera toxin (CT)-challenged and control intestinal loops in the rabbit. CPX
      concentrations were similar in CT-challenged and control jejunal and ileal loops,
      while cecal elimination was negligible. The quantities of eliminated CPX per
      square centimeter of bowel wall were significantly higher in the small intestine
      CT-challenged loops. The mechanism of elimination of CPX in the small intestine
      is therefore mainly passive diffusion.

PMID- 9527814
TI  - QacA multidrug efflux pump from Staphylococcus aureus: comparative analysis of
      resistance to diamidines, biguanidines, and guanylhydrazones.
AB  - The staphylococcal multidrug efflux pump QacA mediates resistance to a broad
      spectrum of monovalent and divalent antimicrobial cations. Resistance toward
      various classes of these compounds identified features of the substrate that may
      be important for interaction with QacA. Analysis of combinations of two
      substrates suggested that the same mechanism is used for the extrusion of
      different classes of compounds.

PMID- 9527815
TI  - Estimate of the frequency of human immunodeficiency virus type 1 protease
      inhibitor resistance within unselected virus populations in vitro.
AB  - The frequency of drug-resistant human immunodeficiency virus type 1 (HIV-1)
      variants in virus populations not previously exposed to drug was determined in
      vitro by using HIV-1RF and the protease inhibitor SC-55389A. Two variants with
      single mutations responsible for drug resistance (V82A and N88S) were
      quantifiably isolated after only one round of replication, yielding a crude
      frequency estimate of at least 1 SC-55389A-resistant variant per 3.5 x 10(5) wild
      type infectious units.

PMID- 9527817
TI  - Nomenclature of genes encoding aminoglycoside-modifying enzymes.

PMID- 9527816
TI  - Bronchopulmonary pharmacokinetics of clarithromycin and azithromycin.

PMID- 9527818
TI  - [Renal hydatid cyst. Report of a new case].
AB  - OBJECTIVES: To report an additional case of renal hydatid cyst in a patient who
      had been clinically asymptomatic despite the significant renal derangement
      observed at diagnosis. METHODS/RESULTS: Patient clinical history is presented and
      the diagnostic methods are described. CONCLUSIONS: US, urography and CT permit an
      accurate diagnosis in most of the cases. MRI has diagnostic limitations in this
      condition. To date, surgery continues to be the treatment of choice.

PMID- 9527819
TI  - [Occult bladder cancer in incarcerated inguinal hernia. Report of a case and
      review of the literature].
AB  - OBJECTIVE: To describe a case of incarcerated inguinal hernia containing bladder
      carcinoma. METHODS/RESULTS: A case of urothelial bladder neoplasm presenting with
      perforation and scrotal abscess is described. The clinical features, incidence
      and diagnostic aspects are discussed and the literature briefly reviewed.
      CONCLUSION: The association of malignant tumor and hernia of the abdominal wall
      is uncommon, particularly those involving the inguinal zone. To our knowledge,
      only 8 cases have been reported from 1965 to 1995, accounting for 5.3% of all
      hernia sac-associated tumors. The location of this type of tumor delays diagnosis
      and the outcome is generally poor.

PMID- 9527821
TI  - [Sexuality and prostate].

PMID- 9527820
TI  - [Idiopathic calcinosis of the scrotum. Cytohistologic diagnosis in biopsy and
      puncture samples].
AB  - OBJECTIVE: To report an uncommon case of idiopathic calcinosis of the scrotum.
      METHODS/RESULTS: A case of idiopathic scrotal calcinosis in a 50-year-old male
      who presented with multiple hard masses in the scrotum is described. Cytological
      (fine needle aspiration) and histological (biopsy and resection) analyses of
      these lesions were performed. CONCLUSIONS: Although the etiopathogenesis of
      scrotal calcinosis remains unknown, the involvement of a dystropic mechanism has
      recently been described. The usefulness of fine needle aspiration, a method that
      has gradually been included in the study of testicular pathology, is underscored.

PMID- 9527822
TI  - [Sclerosing adenosis of the prostate].
AB  - OBJECTIVES: To describe the anatomoclinical characteristics of 4 cases of
      sclerosing adenosis of the prostate in order to determine the diagnostic features
      and clinical significance of this disease entity, which histologically mimicks
      adenocarcinoma of the prostate. METHODS: Specimens from our Pathological Anatomy
      Service obtained by transurethral resection (TUR) and prostatic adenomectomy,
      with a clinical diagnosis of a benign pathology, were reviewed. Three cases with
      a histological diagnosis of sclerosing adenosis of the prostate were found over
      the last 10 years. A fourth case, an adenomectomy specimen corresponding to 1986
      whose initial diagnosis had been changed to that of sclerosing adenosis of the
      prostate, was identified in a review conducted on incidentally detected
      carcinomas Tla. RESULTS: The four cases (2 adenomectomy, 2 TUR specimens) were
      microscopic findings. Patient mean age was 73 years. All cases were associated
      with a nodular hyperplasia, without clinical or analytical signs of malignant
      neoplasm or an associated carcinoma. One case showed involvement of 3 fragments
      of the TUR specimen; the rest had a single focus or involvement of a single
      fragment. At 5 years mean follow-up, no evidence of new lesions have been
      observed. CONCLUSIONS: Sclerosing adenosis of the prostate is an uncommon lesion,
      which is generally microscopic and more frequently found in the prostatic
      transitional zone, and can be confused histologically with microacinar carcinoma.
      It is usually an incidental histopathological finding without clinical
      significance or relationship with carcinoma of the prostate.

PMID- 9527823
TI  - [Diagnosis and surgical treatment of distal urethral stenosis caused by fibrous
      periurethritis in women. Our experience].
AB  - OBJECTIVE: To report on our experience in the diagnosis and surgical treatment of
      distal urethral stenosis arising from fibrous periurethritis in women. METHODS: 9
      patients who had undergone surgery for distal urethral stenosis caused by fibrous
      periurethritis are described. Patient history, clinical symptoms, the surgical
      technique employed, complications and post-operative course are presented.
      RESULTS: All 9 patients had a history of recurrent urinary infection and
      alteration of the urinary stream. The results obtained by surgery were
      satisfactory in all cases. CONCLUSIONS: Distal urethral stenosis arising from
      fibrous periurethritis is uncommon, but not rare. Diagnosis is principally based
      on the clinical symptoms, characterized by low urinary obstructive symptoms, and
      the finding at physical examination of a narrow meatus and periurethral
      enlargement caused by fibrous tissue surrounding the distal urethra. The
      Richardson urethrolysis technique achieved satisfactory results in these
      patients.

PMID- 9527824
TI  - [Local staging with CT of tumors of the upper urothelium].
AB  - OBJECTIVE: To evaluate the ability of computerized tomography (CT) to stage
      transitional cell carcinoma of the upper urinary tract. METHODS: 29 transitional
      cell carcinoma of the upper urinary tract submitted to nephroureterectomy were
      retrospectively evaluated. All 29 tumors had preoperative CT scans performed to
      stage the lesion. The pathological staging was compared to that of CT. RESULTS:
      10 of the 29 tumors had CT evidence of tumor extension and 19 had localized
      noninvasive tumor on CT. Of the 10 patients with CT findings of tumor extension,
      2 (20%) had superficial tumors and 8 (80%) had tumors that invaded into the
      adventitial fat, renal parenchyma or perirenal fat (pT3, pT4). Of the 19 patients
      with localized noninvasive tumor on CT, 13 (68%) had superficial tumors and 6
      (32%) had pT3 or pT4 tumors. CT sensitivity for tumor invasion was 57% with a
      specificity of 87.5%. CONCLUSIONS: Our analysis shows that CT is of limited value
      in staging these tumors. When CT demonstrates direct tumor extension through the
      renal pelvic or ureteral wall, it is a sensitive indicator of high-stage tumor.
      However, the results obtained in low stage tumors must be viewed with caution.

PMID- 9527825
TI  - [Mucinous adenocarcinoma of the prostate. Report of 3 cases and review of the
      literature].
AB  - OBJECTIVES: To describe 3 cases of mucinous adenocarcinoma, an uncommon variant
      of prostatic adenocarcinoma, and review the literature. METHODS: 3 cases of
      mucinous adenocarcinoma of the prostate are described. The histological and
      immunohistochemical features, diagnostic and therapeutic aspects of this variant
      of prostatic adenocarcinoma are presented and the literature briefly reviewed.
      RESULTS/CONCLUSIONS: This variant of prostatic adenocarcinoma is characterized by
      the presence of extra and intracellular mucus formation. It is generally seen in
      the advanced stages and responds poorly to any form of therapy.

PMID- 9527826
TI  - [Bladder pseudosarcoma in pediatrics: clinico-pathological features and
      treatment].
AB  - OBJECTIVES: To review the most common clinical signs and symptoms of inflammatory
      pseudotumor of the bladder in children and to distinguish this benign lesion from
      malignant neoplasms such as rhabdomyosarcoma and leiomyosarcoma. METHODS: Two
      cases os pseudosarcomatous tumor of the bladder in children are described. In the
      first patient, the tumor had appeared spontaneously in a 9-year-old boy. The
      second had developed in a 6-year-old girl and was considered to be reactive to
      prior surgery. The literature is reviewed and data from 16 cases of inflammatory
      pseudotumor of the bladder in patients under 16 years of age are also presented.
      RESULTS: The mean age at presentation was 8 years. The male-to-female ratio was
      3:1. Hematuria (56%), dysuria (37%) and abdominal pain with a palpable mass (18%)
      were the most commonly described clinical manifestations. Tumor size ranged from
      3 to 10 cm and they were frequently located in the lateral walls and base of the
      bladder. Histological analysis showed an inflammatory pseudosarcomatous reaction.
      Immunohistochemical analysis showed moderate staining for vimentin, mild staining
      for focal muscle actin and negative for keratin and S-100 protein. Patients were
      treated by local resection (7 pts), partial cystectomy (5 pts), radical
      cystectomy (2 pts) and pelvic exenteration (2 pts). The mean follow-up was 34
      months. All patients that had been followed (14/16) were reported to be free of
      disease with no evidence of recurrences or metastases. CONCLUSIONS: Inflammatory
      pseudotumor of the bladder is an unusual benign tumor that is very rare in
      children. Long-term follow-up confirms the benign nature of the lesion and
      conservative management is therefore advocated. However, given its histological
      similarity to malignant tumors, a close follow-up is recommended.

PMID- 9527827
TI  - [Value of transrectal ultrasonography in the assessment of failures of stress
      urinary incontinence surgery in women].
AB  - OBJECTIVES: To describe the role of transrectal ultrasonography as an alternative
      imaging technique in the evaluation of women who continue to be incontinent
      following surgical management of female stress urinary incontinence. METHODS: The
      means of independent samples of transrectal ultrasound parameters of two groups
      of patients (group I, patients who were continent after surgery; group II,
      patients who remained incontinent after surgery) were compared. RESULTS: Patients
      who were continent after surgery showed scanty caudal and dorsal mobility of the
      bladder neck and proximal urethra during the periods of increased intraabdominal
      pressure. The US finding in this group of patients is characterized by a funnel
      surrounding the bladder neck and the proximal urethra. The existence of an
      intrinsically incompetent sphincter can also be determined with this technique.
      CONCLUSIONS: Transrectal ultrasonography constitutes an alternative imaging
      technique in the evaluation of women who continue to be incontinent following
      surgical management of female stress urinary incontinence. It permitis
      determining whether incontinence is due to a failed procedure, the existence of
      an intrinsically incompetent sphincter, or whether other causes of incontinence
      should be investigated.

PMID- 9527828
TI  - [Usefulness of magnetic resonance angiography in the diagnosis of polar vessel in
      stenosis of the pyeloureteral junction].
AB  - OBJECTIVES: To present the results of a prospective study that had been conducted
      to determine the accuracy of magnetic resonance angiography (MRA) in the
      detection of accessory or polar vessels associated with ureteropelvic junction
      (UPJ) stricture, in order to utilize the most appropriate surgical procedure in
      the management of this condition. METHODS: From October, 1994 to September, 1996,
      30 MRA procedures were done in 12 males and 18 females, aged 14 to 73 years (mean
      38.12), with symptomatic UPJ obstruction. When the MRA was positive for polar
      vessels, the patients underwent open dismembered pyeloplasty; surgical
      correlation and a true positive result could be established. Percutaneous
      endopyelotomy was offered when the MRA was negative. The findings at open surgery
      and an unremarkable clinical course and radiological findings at one year follow
      up established a true negative result. RESULTS: Accessory or polar vessels (11
      arteries; 4 veins) were found in 11 patients (36.4%). MRA had a sensitivity of
      92.3% (15/16) for detection of accessory vessels. Fourteen patients underwent
      open surgery (11 dismembered pyeloplasties; 3 nephrectomies) and the MRA findings
      were confirmed in each case (8 positive; 6 negative). Surgery disclosed an
      accessory vein that had not been detected on MRA in only one patient. This
      patient also had a polar artery that had been observed on MRA and demonstrated at
      surgery; thus, the sensitivity of MRA for detection of UPJ stenosis with polar
      vessel is 100% (11/11). Each vessel described on MRA was confirmed at surgery;
      there were therefore no false positives and the specificity was 100%.
      CONCLUSIONS: Although this is a preliminary study with a short follow-up and with
      some limitations, the results indicate that MRA is a simple, non-invasive
      technique with a high sensitivity and specificity for detection of polar vessels
      associated with UPJ stenosis, and appears to be a useful preoperative diagnostic
      procedure due to the surgical implications.

PMID- 9527829
TI  - [Extrarenal Wilms' tumor: diagnosis and treatment review regarding a case
      report].
AB  - OBJECTIVES: To report a case of extrarenal Wilms' tumor, an uncommon site of
      presentation of this tumor type. The diagnostic and prognostic aspects of this
      condition are also discussed. METHODS/RESULTS: A case of retroperitoneal
      extrarenal Wilms' tumor in a 2-year-old child is presented. The patient underwent
      surgery and received postoperative chemotherapy. At 3-years' follow-up, no
      evidence of metastasis has been observed. CONCLUSIONS: Extrarenal Wilms' tumor is
      rare and has been reported in the literature principally as case reports. Its
      clinical presentation varies according to the extrarenal localization. The
      procedures utilized to determine the size of the primary tumor, regional node
      involvement and the presence of distant metastasis are similar to those utilized
      in Wilms' tumor of the kidney. Our results demonstrate the utility of
      chemotherapy; the cytostatic agents utilized appear to be as effective as in
      Wilms' tumor of the kidney. In our view, radiotherapy should be reserved for the
      large unresectable residual tumor mass and for distant metastasis.

PMID- 9527830
TI  - Toward a biophysically plausible bidirectional Hebbian rule.
AB  - Although the commonly used quadratic Hebbian-anti-Hebbian rules lead to
      successful models of plasticity and learning, they are inconsistent with
      neurophysiology. Other rules, more physiologically plausible, fail to specify the
      biological mechanism of bidirectionality and the biological mechanism that
      prevents synapses from changing from excitatory to inhibitory, and vice versa. We
      developed a synaptic bidirectional Hebbian rule that does not suffer from these
      problems. This rule was compared with physiological homosynaptic conditions in
      the hippocampus, with the results indicating the consistency of this rule with
      long-term potentiation (LTP) and long-term depression (LTD) phenomenologies. The
      phenomenologies considered included the reversible dynamics of LTP and LTD and
      the effects of N-methyl-D-aspartate blockers and phosphatase inhibitors.

PMID- 9527831
TI  - Axon guidance: stretching gradients to the limit.
AB  - Neuronal growth cones, the sensory-motile structures at the tips of developing
      axons, navigate to their targets over distances that can be many times greater
      than their diameter. They may accomplish this impressive task by following
      spatial gradients of axon guidance molecules in their environment (Bonhoeffer &
      Gierer, 1984; Tessier-Lavigne & Placzek, 1991; Baier & Bonhoeffer, 1994). We
      calculate the optimal shape of a gradient and the distance over which it can be
      detected by a growth cone for two competing mechanistic models of axon guidance.
      The results are surprisingly simple: Regardless of the mechanism, the maximum
      distance is about 1 cm. Since gradients and growth cones have coevolved, we
      suggest that the shape of the gradient in situ will predict the mechanism of
      gradient detection. In addition, we show that the experimentally determined
      dissociation constants for receptor-ligand complexes implicated in axon guidance
      are about optimal with respect to maximizing guidance distance. The relevance of
      these results to the retinotectal system is discussed.

PMID- 9527832
TI  - Equivalence of a sprouting-and-retraction model and correlation-based plasticity
      models of neural development.
AB  - A simple model of correlation-based synaptic plasticity via axonal sprouting and
      retraction (Elliott, Howarth, & Shadbolt, 1996a) is shown to be equivalent to the
      class of correlation-based models (Miller, Keller, & Stryker, 1989), although
      these were formulated in terms of weight modification of anatomically fixed
      synapses. Both models maximize the same measure of synaptic correlation, subject
      to certain constraints on connectivity. Thus, the analyses of the correlation
      based models suffice to characterize the behavior of the sprouting-and-retraction
      model. More detailed models are needed for theoretical distinctions to be drawn
      between plasticity via sprouting and retraction, weight modification, or a
      combination. The model of Elliott et al. involves stochastic search through
      allowed weight patterns for those that improve correlations. That of Miller et
      al. instead follows dynamical equations that determine continuous changes of the
      weights that improve correlations. The identity of these two approaches is shown
      to depend on the use of subtractive constraint enforcement in the models of
      Miller et al. More generally, to model the idea that neural development acts to
      maximize some measure of correlation subject to a constraint on the summed
      synaptic weight, the constraint must be enforced subtractively in a dynamical
      model.

PMID- 9527833
TI  - Axonal processes and neural plasticity: a reply.
AB  - We examine the claim that a class of sprouting-and-retraction models is
      mathematically equivalent to a fixed-anatomy model. We accept, subject to
      important caveats, a narrow mathematical equivalence of the energy functions in
      both classes of model. We argue that this narrow equivalence of energy functions
      does not, however, entail equivalence of the models. Indeed, the claim of
      complete model equivalence hides significant dynamical differences between the
      approaches, which we discuss. We also disagree that our work demonstrates that
      subtractive constraint enforcement is natural in fixed-anatomy models.

PMID- 9527834
TI  - Synaptic delay learning in pulse-coupled neurons.
AB  - We present rules for the unsupervised learning of coincidence between excitatory
      postsynaptic potentials (EPSPs) by the adjustment of postsynaptic delays between
      the transmitter binding and the opening of ion channels. Starting from a gradient
      descent scheme, we develop a robust and more biological threshold rule by which
      EPSPs from different synapses can be gradually pulled into coincidence. The
      synaptic delay changes are determined from the summed potential--at the site
      where the coincidence is to be established--and from postulated synaptic learning
      functions that accompany the individual EPSPs. According to our scheme, templates
      for the detection of spatiotemporal patterns of synaptic activation can be
      learned, which is demonstrated by computer simulation. Finally, we discuss
      possible relations to biological mechanisms.

PMID- 9527835
TI  - Neural processing in the subsecond time range in the temporal cortex.
AB  - The hypothesis that cortical processing of the millisecond time range is
      performed by latency competition between the first spikes produced by neuronal
      populations is analyzed. First, theorems that describe how the mechanism of
      latency competition works in a model cortex are presented. The model is a
      sequence of cortical areas, each of which is an array of neuronal populations
      that laterally inhibit each other. Model neurons are integrate-and-fire neurons.
      Second, the model is applied to the ventral pathway of the temporal lobe, and
      neuronal activity of the superior temporal sulcus of the monkey is reproduced
      with the model pathway. It consists of seven areas: V1, V2/V3, V4, PIT, CIT, AIT,
      and STPa. Neural activity predicted with the model is compared with empirical
      data. There are four main results: (1) Neural responses of the area STPa of the
      model showed the same fast discrimination between stimuli that the corresponding
      responses of the monkey did: both were significant within 5 ms of the response
      onset. (2) The hypothesis requires that the response latency of cortical neurons
      should be shorter for stronger responses. This requirement was verified by both
      the model simulation and the empirical data. (3) The model reproduced fast
      discrimination even when spontaneous random firing of 9 Hz was introduced to all
      the cells. This suggests that the latency competition performed by neuronal
      populations is robust. (4) After the first few competitions, the mechanism of
      latency competition always detected the strongest of input activations with
      different latencies.

PMID- 9527836
TI  - Temporal-code to rate-code conversion by neuronal phase-locked loops.
AB  - Peripheral sensory activity follows the temporal structure of input signals.
      Central sensory processing uses also rate coding, and motor outputs appear to be
      primarily encoded by rate. I propose here a simple, efficient structure,
      converting temporal coding to rate coding by neuronal phase-locked loops (PLL).
      The simplest form of a PLL includes a phase detector (that is, a neuronal
      plausible version of an ideal coincidence detector) and a controllable local
      oscillator that are connected in a negative feedback loop. The phase detector
      compares the firing times of the local oscillator and the input and provides an
      output whose firing rate is monotonically related to the time difference. The
      output rate is fed back to the local oscillator and forces it to phase-lock to
      the input. Every temporal interval at the input is associated with a specific
      pair of output rate and time difference values; the higher the output rate, the
      further the local oscillator is driven from its intrinsic frequency. Sequences of
      input intervals, which by definition encode input information, are thus
      represented by sequences of firing rates at the PLL's output. The most plausible
      implementation of PLL circuits is by thalamocortical loops in which populations
      of thalamic "relay" neurons function as phase detectors that compare the timings
      of cortical oscillators and sensory signals. The output in this case is encoded
      by the thalamic population rate. This article presents and analyzes the
      algorithmic and the implementation levels of the proposed PLL model and describes
      the implementation of the PLL model to the primate tactile system.

PMID- 9527837
TI  - Deformation Theory of Dynamic Link Matching
AB  - Dynamic link matching is a self&hyphenorganizing topographic mapping between a
      template image and a data image. The mapping tends to be continuous, linking two
      points sharing similar local features, which, as a result, can lead to its
      deformation to some degree. In analyzing such deformation mathematically, we
      reduced the model equation to a phase equation, which enabled us to clarify the
      principles of the deformation process and the relationship between
      high&hyphendimensional models and low&hyphendimensional ones. We also elucidated
      the characteristics of the model in the context of the standard regularization
      theory.

PMID- 9527839
TI  - Breaking Rotational Symmetry in a Self&hyphenOrganizing Map Model for Orientation
      Map Development
AB  - We analyze the pattern formation behavior of a high&hyphendimensional
      self&hyphenorganizing map (SOM) model for the competitive projection of
      ON&hyphencenter&hyphentype and OFF&hyphencenter&hyphentype inputs to a common map
      layer. We mathematically show, and numerically confirm, that even isotropic
      stimuli can drive the development of oriented receptive fields and an orientation
      map in this model. This result provides an important missing link in the spectrum
      of pattern formation behaviors observed in SOM models. Extending the model by
      including further layers for binocular inputs, we also investigate the combined
      development of orientation and ocular dominance maps. A parameter region for
      combined patterns exists; corresponding maps show a preference for perpendicular
      intersection angles between iso&hyphenorientation lines and ocularity domain
      boundaries, consistent with experimental observations.

PMID- 9527838
TI  - Constrained optimization for neural map formation: a unifying framework for
      weight growth and normalization.
AB  - Computational models of neural map formation can be considered on at least three
      different levels of abstraction: detailed models including neural activity
      dynamics, weight dynamics that abstract from the neural activity dynamics by an
      adiabatic approximation, and constrained optimization from which equations
      governing weight dynamics can be derived. Constrained optimization uses an
      objective function, from which a weight growth rule can be derived as a gradient
      flow, and some constraints, from which normalization rules are derived. In this
      article, we present an example of how an optimization problem can be derived from
      detailed nonlinear neural dynamics. A systematic investigation reveals how
      different weight dynamics introduced previously can be derived from two types of
      objective function terms and two types of constraints. This includes dynamic link
      matching as a special case of neural map formation. We focus in particular on the
      role of coordinate transformations to derive different weight dynamics from the
      same optimization problem. Several examples illustrate how the constrained
      optimization framework can help in understanding, generating, and comparing
      different models of neural map formation. The techniques used in this analysis
      may also be useful in investigating other types of neural dynamics.

PMID- 9527840
TI  - Nonlinear Time&hyphenSeries Prediction with Missing and Noisy Data
AB  - We derive solutions for the problem of missing and noisy data in nonlinear
      time&hyphenseries prediction from a probabilistic point of view. We discuss
      different approximations to the solutions &hyphen in particular, approximations
      that require either stochastic simulation or the substitution of a single
      estimate for the missing data. We show experimentally that commonly used
      heuristics can lead to suboptimal solutions. We show how error bars for the
      predictions can be derived and how our results can be applied to K&hyphenstep
      prediction. We verify our solutions using two chaotic time series and the sunspot
      data set. In particular, we show that for K&hyphenstep prediction, stochastic
      simulation is superior to simply iterating the predictor.

PMID- 9527841
TI  - Issues in Bayesian Analysis of Neural Network Models
AB  - Stemming from work by Buntine and Weigend (1991) and MacKay (1992), there is a
      growing interest in Bayesian analysis of neural network models. Although
      conceptually simple, this problem is computationally involved. We suggest a very
      efficient Markov chain Monte Carlo scheme for inference and prediction with
      fixed&hyphenarchitecture feedforward neural networks. The scheme is then extended
      to the variable architecture case, providing a data&hyphendriven procedure to
      identify sensible architectures.

PMID- 9527842
TI  - An integrated approach to proteome analysis: identification of proteins
      associated with cardiac hypertrophy.
AB  - Hypertrophy of cardiac myocytes is a primary response of the heart to overload,
      and is an independent predictor of heart failure and death. Distinct cellular
      phenotypes are associated with hypertrophy resulting from different causes. These
      phenotypes have been described by others at the molecular level by analysis of
      gene transcription patterns. An alternative approach is the analysis of large
      scale protein expression patterns (the proteome) by two-dimensional
      polyacrylamide gel electrophoresis. Realization of this goal requires the ability
      to rigorously analyze complex 2D gel images, efficiently digest individual gel
      isolated proteins (especially those expressed at low levels), and analyze the
      resulting peptides with high sensitivity for rapid database searches. We have
      undertaken to improve the technology and experimental approaches to these
      challenges in order to effectively study a cell culture model for cardiac
      hypertrophy. The 2D gel patterns for cell lysates from multiple samples of
      cardiac myocytes with or without phenylephrine-induced hypertrophy were analyzed
      and spots which changed in abundance with statistical significance were located.
      Eleven such spots were identified using improved procedures for in-gel digestion
      of silver-stained proteins and high-sensitivity mass spectrometry. The
      incorporation of low levels of sodium dodecyl sulfate into the digestion buffer
      improved peptide recovery. The combination of matrix-assisted laser desorption
      mass spectrometry for initial measurements and capillary liquid chromatography
      ion trap mass spectrometry for peptide sequence determination yielded efficient
      protein identification. The integration of 2D gel image analysis and routine
      identification of proteins present in gels at the subpicomole level represents a
      general model for proteome studies relating genomic sequence with protein
      expression patterns.

PMID- 9527843
TI  - Affinity selection from peptide libraries to determine substrate specificity of
      protein tyrosine phosphatases.
AB  - Affinity selection from peptide libraries is a powerful tool that has been used
      for determining the sequence specificities of a number of enzymes and protein
      binding domains, including protein kinases, src homology 2 domains, and PDZ
      domains. We have extended this approach to protein tyrosine phosphatases using
      peptide libraries containing a nonhydrolyzable phosphotyrosine analog,
      difluorophosphonomethylphenylalanine. A size-exclusion method is used to separate
      enzyme-peptide complexes from free peptide, providing several advantages over the
      traditional immobilized protein affinity column approach. In addition, the
      feasibility of using mass spectrometric detection to quantitate peptides rapidly
      and reproducibly is demonstrated as an alternative to quantitation by peptide
      sequencing. The validity of this analysis is demonstrated by synthesizing
      individual peptides and comparing their affinity for enzyme with the predictions
      from the affinity selection process. As a model for these studies the protein
      tyrosine phosphatase PTP1B is used, providing additional insights into the
      sequence specificity of this enzyme. In particular, a selection for aromatic
      amino acids at the pY - 1 position (immediately N-terminal to the
      phosphotyrosine), as well as a broad pY + 1 selectivity, is observed in addition
      to the general preference for acidic residues N-terminal to the phosphotyrosine.
      The approach described here should prove applicable to protein tyrosine
      phosphatases in general as well as for the study of nonpeptidyl combinatorial
      libraries.

PMID- 9527844
TI  - Base specificity of oligonucleotide digestion by calf spleen phosphodiesterase
      with matrix-assisted laser desorption ionization analysis.
AB  - Calf spleen phosphodiesterase cleaves oligonucleotide strands in a stepwise
      manner from the 5' end and can be used in combination with matrix-assisted laser
      desorption ionization (MALDI) mass spectrometry to perform ladder sequencing. The
      relative intensities of ladder peaks in the mass spectra of a series of 5-mers
      and 7-mers show that the rate of digestion is influenced by strand sequence.
      Sequences terminating in A or G at the 5' end are found to react two to three
      times faster than sequences terminating in C or T. The reactivity of the terminal
      base is also influenced by the sequence beyond the 5' end. When the third base
      from the 5' end is A or G, removal of the first and second bases is faster than
      when the third base is C or T. A method is described which permits reaction rates
      to be quantitatively determined from the time dependences of ladder peaks in the
      MALDI spectra. A similar approach could be used for mechanistic studies.

PMID- 9527845
TI  - Visualization of proteins by modification of lysines, cysteines, and
      phosphorylated serines facilitates sample preparation for microsequencing.
AB  - A procedure for visualization and sensitive detection of protein during sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and subsequent
      sample preparation for sequence analysis is described. This procedure utilizes
      either fluorescent or visible tags for certain amino acids in protein molecules,
      e.g., lysines modified with dansyl/dabsyl chloride and cystines/cysteines or
      phosphorylated serines modified with iodoacetamidofluorescein (I-15) after proper
      sample pretreatments. Modifications are performed prior to SDS-PAGE, eliminating
      the need for fixing, staining, and destaining as required for the conventional
      procedures. After electrophoresis, the fluorescent or visible bands are excised
      from the gel, homogenized in microcentrifuge tubes, and soaked in an appropriate
      buffer to release the separated proteins into solution. Enzymatic digestion can
      then be carried out in solution for better efficiency of digestion and recovery.
      The subsequent HPLC mapping and collection of protein digests are performed on PE
      Applied Biosystems Model 173A MicroBlotter. The separated peptides containing
      tagged amino acids are visible on the PVDF membrane and can be excised for direct
      sequence analysis. This approach has been employed for selectively isolating the
      lysine, cysteine, or phosphorylated serine containing peptides using model
      proteins. The sequencing results of the peptides generated from premodified
      proteins demonstrate that this approach facilitates sample preparation for
      microsequence analysis at low picomole level. Overall recoveries of 20-30% by
      sequencing initial yields have been achieved using our model proteins.

PMID- 9527846
TI  - Enzymatic synthesis of [3H]Cytidine 5'-diphospho-1, 2-diacyl-sn-glycerol.
AB  - Cytidine 5'-diphospho-1,2-diacyl-sn-glycerol (CDP-diacylglycerol; CDP-DG) is an
      important intermediate in the biosynthesis of the major glycerophosphate-based
      phospholipids of prokaryotes and eukaryotes. This compound is expensive to
      purchase and inefficient to prepare chemically. Radiolabeled CDP-diacylglycerol
      is unavailable commercially. We describe a simple and inexpensive method to
      synthesize [3H]CDP-DG enzymatically. The three-step enzymatic procedure includes
      phosphorylation of [3H]glycerol to sn-[3H]glycerol 3-phosphate (G3P) by
      glycerokinase,acylation of [3H]G3P to [3H]phosphatidic acid (PA) by G3P
      acyltransferase, and conversion of [3H]PA and CTP to [3H]CDP-DG by CDP-DG
      synthase. This procedure is considerably less labor intensive and less expensive
      than is chemical synthesis, and the yield is at least 30%.

PMID- 9527847
TI  - Assay of 25-hydroxyvitamin D3 1 alpha-hydroxylase in rat kidney mitochondria.
AB  - An assay method for 25-hydroxyvitamin D3 1alpha-hydroxylase [calcidiol, NADPH:
      oxygen oxidoreductase (1-hydroxylating), EC 1.14. 13.13] in rat kidney is
      described. The mitochondrial and nuclear fraction was solubilized effectively
      with 3-[(3-cholamidopropyl)-dimethylammonio]-1-propanesulfonate(Chaps). By
      subsequent ultracentrifugation of the solubilized suspension the effect of
      inhibitory factor(s) in mammals was removed. The enzyme was then assayed by the
      reconstitution method using saturated amounts of adrenodoxin and NADPH
      adrenodoxin reductase. Products were analyzed by HPLC, monitoring absorbance at
      265 nm. The enzyme activity depended on not only pH of the medium but also the
      kind of buffers. N,N-Bis(2-hydroxyethyl)glycine was the best buffer. At 30
      degrees C, the reaction velocity was linear at least up to 10 min, by which time
      enough amounts of the product needed for analysis were formed. The enzyme
      activity was linear to a protein concentration up to 0.8 mg of protein/ml. Under
      the best assay conditions established, the maximal velocity of enzyme in the
      rachitic rat was 12.9 pmol of product/min/mg of protein, which was 30- to 1000
      fold higher than those reported by other authors with the enzyme of rachitic rat.
      Michaelis constant was 1.8 microM. Specific activity with the enzyme of normal
      rat was 0.25 pmol of product/min/mg.

PMID- 9527848
TI  - Measurement of the activity of polyuronic acid C-5 epimerases.
AB  - A relatively simple assay procedure for measuring the reactions catalyzed by
      polyuronic acid C-5 epimerases has been developed. Action of C-5 epimerases
      inverts the C-6 carboxyl group of polyuronic acids converting beta-linked
      residues into alpha-linked residues or vice versa. The assay takes advantage of
      the greater susceptibility of the acid hydrolysis of alpha-glycosidic linkages
      than beta-glycosidic linkages. The method involves the partial acid hydrolysis of
      the polyuronic acid before and after reaction with the C-5 epimerase. The greater
      or lesser amounts of uronic acid released (solubilized) before and after reaction
      of the C-5 epimerase are a measure of the amount of alpha- or beta-glycosidic
      linkages that are formed and a measure of the amount of catalysis by the enzyme.

PMID- 9527849
TI  - Measurement of Na+, K+-ATPase activity in human skeletal muscle.
AB  - There are few published measures of Na+,K+-ATPase activity in human skeletal
      muscle. This study investigated the suitability of the K+-stimulated 3-O
      methylfluorescein phosphatase assay for measurement of Na+,K+-ATPase activity in
      human skeletal muscle. Factors investigated include enzyme kinetics, sample
      treatment, and ligand concentration. The addition of ouabain blocked maximal K+
      stimulated 3-O-methylfluorescein phosphatase (3-O-MFPase) activity, confirming
      the specificity of the assay. Activity was maximal using a multiple freeze-thaw
      treatment of the homogenate, a 10 mM KCl activating concentration, and a 3-O
      methylfluorescein phosphatase substrate concentration of 160 microM, which is
      eight times higher than previously reported. From quadriceps muscle biopsies
      taken from seven healthy untrained subjects, the maximal K+-stimulated 3-O-MFPase
      activity determined from the homogenates was (mean +/- SE) 292 +/- 10 nmol min-1
      . g-1 wet wt (1745 +/- 84 pmol min-1 . mg-1 protein). This value is five times
      greater than previously published data for human skeletal muscle. The intra-assay
      variability was 8.1% and the interassay variability was 5.3%. These modifications
      greatly enhanced the 3-O-MFPase assay, with the improved enzymatic conditions
      allowing valid, reliable measurement of Na+,K+-ATPase activity in small samples
      of human skeletal muscle.

PMID- 9527851
TI  - The rate zonal separation of organelles from dilute suspensions: the problem of a
      large sample volume.
AB  - Transport vesicles that deliver proteins to the cell surface can be isolated by
      incubating cells that have been permeabilized by mechanical or chemical
      techniques in a high-K medium containing an ATP regenerating system. The vesicles
      released from permeabilized cells are, however, obtained as a very dilute
      suspension in the incubation solution. This presents a problem for the
      preparative separation of specific populations of vesicles by velocity
      sedimentation, because the small sample volume capacity of traditional glycerol
      or sucrose velocity gradients requires that the vesicles first be concentrated by
      sedimentation or that very small amounts of vesicles be loaded onto a gradient.
      We have addressed the problem of the loss of zonal resolution produced by the
      loading of large sample volumes, and we propose that high-viscosity Ficoll
      gradients can be used effectively to restore the resolution of zones when
      substantially larger sample volumes of dilute suspensions must be loaded onto
      velocity gradients.

PMID- 9527850
TI  - Electrochemical determination of S-nitrosothiols with a Clark-type nitric oxide
      electrode.
AB  - Low-molecular-mass thiols and nitric oxide (NO) form S-nitrosothiols
      (thionitrites) in the presence of oxygen. Thionitrites play an integral role in a
      variety of NO-dependent physiological processes. This study describes a sensitive
      analytical method for the quantitative determination of thionitrites. The method
      is based on the Cu+-catalyzed homolytic cleavage of thionitrites and
      electrochemical detection of the released NO with a Clark-type electrode. Cu+ was
      generated by addition of Cu(NO3)2 to samples containing 1 mM GSH or 4 mM L
      cysteine as reducing agents. The effect of Cu(NO3)2 on the release of NO from
      GSNO was concentration-dependent. In the presence of 1 mM GSH, the EC50 for
      Cu(NO3)2 was 1.34 +/- 0.08 mM. Using cysteine instead of GSH, NO release was
      quantitative at much lower concentrations of Cu(NO3)2 (EC50 = 8.5 +/- 2.8 microM.
      NO release was not significantly affected by pH (7.0-9.0) and was inhibited by
      the Cu+-selective chelator neocuproine, whereas the Cu2+ chelator cuprizone was
      approximately 16-fold less potent. Calibration of the method with GSNO, S-nitroso
      N-acetyl-penicillamine, or S-nitrosated bovine serum albumin yielded linear plots
      of initial rates of NO release versus thionitrite concentration from 50 nM to 5
      microM. This method may be useful for the quantitative determination of
      thionitrites in biological samples.

PMID- 9527852
TI  - Determination of glycerol concentrations and glycerol isotopic enrichments in
      human plasma by gas chromatography/mass spectrometry.
AB  - An analytical method is presented to determine glycerol concentrations and stable
      isotope tracer enrichments in human plasma after intravenous tracer infusion in a
      single analytical run, using gas chromatography coupled to mass spectrometry. The
      method uses an internal standard, which is also a stable isotope labeled form of
      glycerol. Three substances were tested as model compounds viz. [2-13C]glycerol,
      and [1,2,3-13C3]glycerol, and [1,1,2,3, 3-2H5]glycerol. Any combination of two
      can be used (one as internal standard, one as tracer), even if overlapping of the
      mass spectra occurs. The method is precise (recovery of spiked glycerol and
      tracer are, respectively, 99.7 and 99.8%) and reproducible (intraassay variation
      <1.5%, interassay variation <6%) and needs only a small amount of plasma (100
      microl).

PMID- 9527853
TI  - Capillary electrophoresis of insulin-like growth factors: enhanced ultraviolet
      detection using dynamically coated capillaries and on-line solid-phase
      extraction.
AB  - Insulin-like growth factor-I and -II (IGF-I and IGF-II) are difficult to separate
      and measure as a result of their homology, both structurally and immunologically.
      A number of binding proteins (BPs) which interact with the IGFs with high
      affinity complicate the ability to measure the IGFs accurately and reproducibly.
      Current methodology for measuring IGF is immuno-based and involves dissociation
      from the IGFs and removal of the binding proteins through sample acidification
      and removal by solid-phase adsorption. However, the net result is an assay that
      is time-consuming and, at best, semiquantitative. In an attempt to improve the
      reproducibility and accuracy of IGF-I and -II measurement, electrophoretic
      systems employing dynamically coated and bare silica capillaries were evaluated.
      Separations in bare silica capillaries in the presence or absence of the cationic
      additive, decamethonium bromide were ineffective for resolving IGF-I and IGF-II.
      However, when the capillary was coated dynamically with polybrene, IGF-I and -II
      could be resolved in a BSA sample matrix using a low pH buffer. Despite the fact
      that the IGFs could be resolved in the presence of an IGF-I analog used as an
      internal standard, polybrene recoating was required after as few as 12 runs and
      poor coating-to-coating reproducibility was observed. Use of
      polydiallyldimethylammonium chloride (PDMAC) as a dynamic cationic coating and a
      low pH buffer containing 0.5% PDMAC was found to be much more effective,
      providing reproducible separation of IGF-I and -II. It was found that PDMAC need
      not be included in the separation buffer to obtain reproducible analyses
      regarding IGF separation. Subsequently, functionality remained intact for as many
      as 35-40 consecutive analyses before recoating was required. Without the need for
      PDMAC in the buffer, on-line solid-phase extraction-capillary electrophoresis
      could be accomplished for detection of IGF-I and -II at concentrations as low 195
      ng/ml.

PMID- 9527854
TI  - Genetic recombination as a reporter for screening steroid receptor agonists and
      antagonists.
AB  - Reporter cell lines are often used for high throughput screening of chemical
      libraries to identify new receptor ligands. Here we show how Cre recombinase can
      be used in mammalian cells to screen for steroid receptor ligands. A
      translational fusion of Cre recombinase and the ligand binding domain of the
      human glucocorticoid receptor was transfected into mammalian cells with a
      loxP/luciferase reporter gene. The recombinase function of the fusion is
      dependent on ligand binding to the receptor, and Cre-mediated recombination
      results in constitutive expression of luciferase from the reporter gene. A stable
      transfected clone was isolated and used to characterize the kinetics, ligand
      specificity, and dose response to various receptor ligands. The Cre fusion
      system, unlike a transcriptional reporter using the mouse mammary tumor virus
      promoter, can detect binding of the receptor antagonist RU486. We also studied
      the Cre reporter in a sensitive, miniaturized, assay format using an 864-well
      plate and show that as few as 560 cells per assay well was sufficient to measure
      a dose response to ligand.

PMID- 9527855
TI  - Determination of galactose and galactocerebroside using a galactose oxidase
      column and electrochemical detector.
AB  - A method has been developed to measure galactose and galactocerebroside using
      galactose oxidase immobilized on a solid resin. Galactose oxidase converts
      galactose and galactocerebroside to their corresponding aldehydes and hydrogen
      peroxide, the latter being electroactive and measurable by electrochemical
      detection using DC amperometric detection. The minimal detection limits of
      galactose and galactocerebroside were 1 and 2 microM, respectively. The linear
      response to galactose and galactocerebroside was to at least 300 microM. About
      100 samples can be measured per hour using flow injection analysis. The activity
      of sulfatidase (cerebroside-3-sulfate-3-sulfohydrolase), which converts sulfatide
      (sulfogalactocerebroside) to galactocerebroside, was measured, and its inhibition
      by O-phospho-L-tyrosine was determined.

PMID- 9527856
TI  - High-resolution separation and quantification of neutral lipid and phospholipid
      species in mammalian cells and sera by multi-one-dimensional thin-layer
      chromatography.
AB  - An improvement of current methods is needed for simple, rapid, and precise
      quantification of cellular lipids, including rare species of biologically active
      cellular lipids, such as phosphatidic acid (PA) and diradylglycerol (DG). In
      addition, further analysis of hydrolyzed acyl chains from these species by
      methods such as gas chromatography requires complete separations. Methods have
      been developed for the quantification of neutral lipids and several phospholipids
      extracted from mammalian cells and sera. Lipid masses were determined for the
      major classes of the neutral, nonpolar lipids, and of the phospholipids. The
      lipid classes were separated by a multistep thin-layer chromatography (TLC)
      procedure in different solvent systems, a method which we have designated as
      multi-one-dimensional thin-layer chromatography (MOD-TLC). Resolved lipid bands
      were visualized by the lipophilic dye primulin (direct yellow 59) and scanned by
      an automated laser-fluorescence detector. The mass of each band was determined by
      comparing band intensities of unknown samples to dilution curves of authentic
      standards. With modifications in solvent mixtures and length of separation times,
      the majority of biological lipids could be resolved and quantified with MOD-TLC
      methods. Since the detection method is nondestructive, purified lipids could then
      be recovered by scraping the visualized bands and extracting the lipids from the
      silica. The structural identities of the recovered lipids were confirmed by fast
      atom bombardment and electrospray mass spectrometry. Extracted lipids were also
      hydrolyzed to release acyl chains and acyl chain species were determined in
      comparison to authentic standards by gas chromatography. PA and DG levels in
      ECV.304 cells were found to be 4. 6 and 3.3%, respectively, of PC levels, with a
      PA/DG ratio of 1.4, which is in accord with published experience using other
      methods and different cell types. PA in human serum was detected at 0.6% of PC,
      indicating the sensitivity of the technique. In contrast to two-dimensional thin
      layer chromatography, which allows for good resolution of some lipid species, but
      cannot be used to analyze more than a single experimental point per plate, MOD
      TLC allows for direct comparative analysis of multiple samples on a single TLC
      plate, while still providing good resolution for the quantification of most major
      classes of lipid species.

PMID- 9527857
TI  - Protein conformational changes determined by matrix-assisted laser desorption
      mass spectrometry.
AB  - It is shown that simultaneously to the unfolding of hen egg white lysozyme and
      horse heart cytochrome c the sequential conformational changes and molten globule
      states can be detected by the combination of proteolysis and matrix-assisted
      laser desorption/ionization mass spectrometry (MALDI-MS). This is demonstrated by
      the differences among the products and the time courses of native lysozyme as
      well as those unfolded in 1 and 3 M guanidine hydrochloride (GuHCl) when they
      were proteolyzed by proteinase K and analyzed by MALDI-MS. Due to the absence of
      disulfide bonds in the cytochrome c molecule, it is more sensitive to the
      disturbance of the denaturant. The partially unfolded state as detected at low
      concentrations of guanidine hydrochloride in our experiment resemble the molten
      globule state. One of the unique properties of the method described herein is to
      measure directly the peptide fragment liberated from proteolysis of the protein.
      It allows the identification of the sensitive sites susceptible to denaturation,
      which are subsequently cleaved by proteinase K proteolysis.

PMID- 9527858
TI  - Scintillation proximity assay for E-, P-, and L-selectin utilizing polyacrylamide
      based neoglycoconjugates as ligands.
AB  - In this study, a novel scintillation proximity assay (SPA) that uses radiolabeled
      soluble neoglycoconjugates as synthetic alternatives to the natural E-, P-, and L
      selectin counterligands was developed. The neoglycoconjugates contained sialyl
      LewisX or sialyl LewisA attached via a three-carbon spacer to a poly[N
      (hydroxyethyl)acrylamide] backbone, thus presenting the carbohydrates in a
      multivalent form. Selectin-ZZ fusion proteins were immobilized on anti-rabbit IgG
      coated SPA beads via a rabbit IgG bridge. The neoglycoconjugate ligands bound to
      all three bead-immobilized selectins, with the highest binding levels apparent
      with E-selectin. Saturation binding studies with E-selectin revealed a complex
      interaction indicative of two or more binding affinities. The response to
      carbohydrate inhibitors was comparable in E-selectin assays that used either the
      neoglycoconjugates or the tritium-labeled HL60 cells as selectin counterligands.
      The incorporation of tyrosine sulfate groups into the backbone of the
      neoglycoconjugate resulted in enhanced binding avidity to both P- and L-selectin,
      indicating that the sulfate-containing neoglycoconjugates are viable synthetic
      mimics of the natural P- and L-selectin counterligands. The use of these
      radiolabeled neoglycoconjugates in conjunction with SPA results in a format
      ideally suited for the high-throughput screening for selectin antagonists.
      Furthermore, this approach can potentially be used to measure other low-avidity
      lectin-carbohydrate interactions.

PMID- 9527860
TI  - Sequence-independent method for in vitro generation of nested deletions for
      sequencing large DNA fragments.

PMID- 9527859
TI  - Hydroxylation of Lys residues reduces their susceptibility to digestion by
      trypsin and lysyl endopeptidase.

PMID- 9527861
TI  - Transfection assay for dual determination of toxicity and gene expression.

PMID- 9527862
TI  - Effect of vanadate on different forms of Coomassie brilliant blue and protein
      assay.

PMID- 9527863
TI  - A luminol/iodophenol chemiluminescent detection system for western immunoblots.

PMID- 9527864
TI  - Modification of the Coomassie brilliant blue staining method for sphingolipids
      and sphingolipid synthesis inhibitors on silica gel thin-layer plate.

PMID- 9527865
TI  - A pressure-extrusion method for DNA extraction from agarose gels.

PMID- 9527866
TI  - Enzymatic quantitation of cholesterol esters in lipid extracts.

PMID- 9527867
TI  - Multichannel pipettor performance verified by measuring pathlength of reagent
      dispensed into a microplate.

PMID- 9527868
TI  - 125I-Labeling and functional evaluation of [Tyr36]parathyroid hormone-related
      peptide(1-36).

PMID- 9527869
TI  - Cold stress responses in mesophilic bacteria.
AB  - The diversity of the prokaryotes that have been studied, combined with the many
      different effects of low temperature, has led to an extensive literature
      concerning cold stress responses in mesophilic bacteria. The aim of this review
      is to discuss the effects of cold on the behavior of bacteria. The following
      three responses will be described: (i) biochemical modifications consisting first
      of membrane fatty acid desaturation and second of the synthesis of cold stress
      proteins, (ii) physiological responses of the cells to permit growth at low
      temperatures above 0 degrees C and cryotolerance at lower temperatures, and (iii)
      control of the cold shock response at a transcriptional and/or translational
      level. This paper reviews knowledge, most of which has been acquired in the last
      10 years, in the field of cold stress responses. It is hoped that these data will
      help to focus attention on the metabolic responses associated with environmental
      disturbance.

PMID- 9527870
TI  - Some insight into the physical basis of the cryoprotective action of dimethyl
      sulfoxide and ethylene glycol.
AB  - In the determination of the solid-liquid phase equilibria in the aqueous mixtures
      of dimethyl sulfoxide (Me2SO) and ethylene glycol (EG) one often encounters the
      problem of equilibrium crystallization. In the present report the above aqueous
      solutions are equilibrated for crystallization in a dielectric cell during which
      the dielectric method is used for monitoring the extent of crystallization. The
      melting temperatures are then measured by using the dielectric technique in
      combination with the differential scanning calorimeter. The equilibrium phase
      diagram of Me2SO is found to be eutectic with two compounds formed of water and
      Me2SO in the ratio of 3:1 and 2:1. In the case of EG solutions it is eutectic
      with a 1:1 compound formation. It is suggested that the greater depression of the
      freezing point of water due to the complex formation and hence the attendant
      increase in the viscosity near the freezing point is the reason for the sluggish
      crystallization in these solutions. The variation of the glass transition
      temperature with composition is also examined in the above solutions along with
      the aqueous solutions of a number of other cryoprotectants. The glass-forming
      tendency of these solutions is discussed in terms of complex formation. An
      attempt is made to distinguish between good and bad glass-forming additives in
      terms of complex formation and ice clathrate formation.

PMID- 9527871
TI  - Metabolic adaptations of a lower vertebrate to long-term hypothermic hypoxia
      provide clues to successful clinical liver preservation.
AB  - This study was designed to determine whether the metabolic adaptations developed
      by frogs to tolerate natural events of hypothermic hypoxia would precondition its
      liver for ex vivo organ storage. The metabolic responses of the frog, Rana
      castabiena, were compared to those of a mammalian system (rat) throughout a
      prolonged period of organ storage. Livers from rats and frogs were flushed and
      stored in UW solution at 5 degrees C for periods of 24-96 h. In frog livers, ATP
      was maintained high and constant over the first 24 h of storage; values ranged
      from 2.7 to 3.0 micro mol/g. Even after 96 h cold storage, ATP remained > 1.0
      micro mol/g. In contrast, ATP levels in stored rat livers dropped rapidly, and by
      4 h ATP was 1.2 micro mol/g. In terms of anaerobic endproduct accumulation,
      lactate levels rose 5.8 micro mol/g in frog liver (over 96 h) and by 8.6 micro
      mol/g in rat liver (over 24 h). This difference in flux through glycolysis was
      also reflected in relative rates of carbohydrate catabolism (i.e., glucose +
      lactate production). The rate of carbohydrate catabolism for frog liver was 0.74
      micro mol/g/h compared to 2.26 micro mol/g/h for rat liver; a Q10 value of 6.2
      was estimated for livers from R. castabiena. An assessment of glycolytic enzyme
      activities revealed that key differences in the responsiveness of pyruvate kinase
      to allosteric modifiers may have been responsible for the marked drop in the rate
      of anaerobic energy production in frog tissues. Although the concept of depressed
      metabolism in a lower vertebrate is not new, the data presented in this study
      demonstrate that a depressed metabolic state can be achieved in isolated livers
      from R. castabiena simply through cold exposure. With respect to clinical
      relevance, the results of this study indicate that energetics of stored livers
      can be maintained effectively through an efficient reduction in energy use in
      combination with a slow, yet continuous, rate of energy production facilitated by
      glycolysis.

PMID- 9527872
TI  - Microscopic analysis of NADH fluorescence during aerobic and anaerobic liver
      preservation conditions: A noninvasive technique for assessment of hepatic
      metabolism.
AB  - Gaseous insufflation of oxygen via the venous vascular system is thought to be an
      useful tool for preventing anoxic tissue injury during extended time periods of
      ischemic preservation and for allowing for an improved recovery of organ function
      after transplantation. The present study aimed at the application of a
      noninvasive technique for monitoring effectiveness and homogeneity of gaseous
      areation by using an epiillumination microscopic technique for assessment of
      tissue nicotinamide adenine dinucleotide (NADH) fluorescence. Rat livers were
      flushed with and stored in University of Wisconsin solution at 4 degrees C for 48
      h (n = 20). In half of the experiments (n = 10) gaseous oxygen was applied
      subsequent to organ harvest. Using ultraviolet-excitation high-resolution
      microscopy and computer-assisted image analysis liver surfaces were scanned for
      NADH intensity and spatial heterogeneity at 1, 24, and 48 h preservation time.
      Livers simply stored without aeration served as controls (n = 10). NADH intensity
      data were compared with corresponding data of tissue adenosine triphosphate (ATP)
      concentrations determined enzymatically. NADH fluorescence already differed at 1
      h preservation between the two groups with significantly lower values in the
      aerobically stored livers. NADH fluorescence further decreased between 1 and 24 h
      preservation and remained low until 48 h, whereas in the anaerobically stored
      livers NADH fluorescence was found to be constantly high over the entire
      observation period. Aerobic storage resulted in rather homogeneous tissue
      oxygenation with an intrahepatic variation of NADH fluorescence <20%. In
      parallel, oxygen persufflation appropriately restored tissue ATP content within 1
      to 24 h of preservation, while the simply stored livers exhibited pronounced
      depletion of ATP. We demonstrate for the first time that by means of retrograde
      gaseous oxygenation, ischemic livers can be readily and effectively oxygenated.
      Our study further indicates that the noninvasive microscopic analysis of tissue
      NADH fluorescence may be an useful tool for estimating efficiency of strategies
      in organ preservation.

PMID- 9527873
TI  - Altered membrane skeleton of hydroxyethylstarch-cryopreserved human erythrocytes.
AB  - Attempts have been made to use hydroxyethylstarch (HES) as an alternative to
      glycerol for cryopreservation of erythrocytes. However, HES cryopreservation
      causes significant transient rheological alterations in erythrocytes. Membrane
      proteins play a critical role for erythrocyte rheology. This study was undertaken
      to analyze erythrocyte membrane proteins during HES cryopreservation. Erythrocyte
      membranes with submembrane skeleton (ghosts) and the submembrane skeleton alone
      (unstripped skeletons) were prepared before freezing (native), after thawing and
      following 3 h reconditioning in glucose-enriched Ringer's solution (Ringer plus
      glucose), or in autologous fresh frozen plasma (AFFP). After electrophoresis
      protein concentrations (percentage of total protein) were determined by
      densitometry. In ghosts, no significant changes were found, whereas in unstripped
      skeletons the following results could be seen: beta-Spectrin: 31.8 +/- 2.2%
      (native), 22.1 +/- 0.8% (postthawing, P < 0.05 vs native), 22.4 +/- 1.6% (Ringer
      plus glucose, P < 0.05 vs native), 31.0 +/- 2.8% (AFFP). Other proteins remained
      unchanged. Since a significant decrease in beta-spectrin concentration after HES
      cryopreservation and after subsequent reconditioning in Ringer's solution with
      glucose was only detected in unstripped skeletons, this cannot be interpreted as
      in vivo protein loss. More likely, HES cryopreservation may have created changes
      in protein-protein associations. The course of beta-spectrin concentration
      parallels certain rheological and biochemical changes and might explain the
      transient rheological changes seen after HES cryopreservation.

PMID- 9527874
TI  - Measurement of water transport during freezing in cell suspensions using a
      differential scanning calorimeter.
AB  - A new technique using a differential scanning calorimeter (DSC) was developed to
      obtain dynamic and quantitative water transport data in cell suspensions during
      freezing. The model system investigated was a nonattached spherical lymphocyte
      (Epstein-Barr virus transformed, EBVT) human cell line. Data from the technique
      show that the initial heat release of a prenucleated sample containing
      osmotically active cells in media is greater than the final heat release of an
      identical sample of osmotically inactive or lysed cells in media. The total
      integrated magnitude of this difference, Deltaqdsc, was found to be proportional
      to the cytocrit and hence also to the supercooled water volume in the sample.
      Further, the normalized fractional integrated heat release difference as a
      function of temperature, Deltaq(T)dsc/Deltaqdsc, was shown to correlate with the
      amount of supercooled cellular water which had exosmosed from the cell as a
      function of subzero temperature at constant cooling rates of 5, 10, and 20
      degrees C/min. Several important limitations of the technique are (1) that it
      requires a priori knowledge of geometric parameters such as the surface area,
      initial volume, and osmotically inactive cell volume and (2) that the technique
      alone cannot determine whether the heat released from supercooled cellular water
      is due to dehydration or intracellular ice formation. Cryomicroscopy was used to
      address these limitations. The initial cell volume and surface area were obtained
      directly whereas a Boyle-van't Hoff (BVH) plot was constructed to obtain the
      osmotically inactive cell volume Vb. Curve fitting the BVH data assuming linear
      osmometric behavior yielded Vb = 0.258V0; however, nonlinearity in the data
      suggests that the EBVT lymphocyte cells are not "ideal osmometers" at low subzero
      temperatures and created some uncertainty in the actual value of Vb.
      Cryomicroscopy further confirmed that dehydration was the predominant biophysical
      response of the cells over the range of cooling rates investigated. One notable
      exception occurred at a rate of 20 degrees C/min where evidence for intracellular
      ice formation due to a DSC measured heat release between -30 and -34 degrees C
      correlated with a higher end volume but no darkening of the cells during
      cryomicroscopy. For the cooling rate tested (5 degrees C/min) the cryomicroscopy
      data correlated statistically very well with the DSC water transport data. A
      model of water transport was fit to the DSC water transport data and the average
      (5, 10, and 20 degrees C/min) biophysical parameters for the EBVT lymphocytes
      were found to be Lpg = 0.10 micro m/min-atm, ELp = 15.5 kcal/mol. Finally, the
      decrease in heat release from osmotically active cells measured by the DSC during
      repetitive freezing and thawing was found to correlate strongly with the
      viability of the cells measured during identical freeze/thaw protocols with
      cryomicroscopy. This shows the additional ability of the technique to assess
      freeze/thaw injury. In summary, this DSC technique is a promising new approach
      for measuring water transport in cellular systems during freezing.

PMID- 9527875
TI  - Thermal characteristics of a hepatic cryolesion formed in vitro by a 3-mm
      implantable cryoprobe.
AB  - The objective of the investigation was to characterize the hepatic cryolesion
      formed with an implantable needle (3 x 100 mm) cryoprobe. This was used to
      produce cryolesions in isolated porcine liver tissue equilibrated to 37 degrees C
      in a water bath. The shape, size, and temperature zones within the cryolesion and
      the effect of single versus repeated freeze-thaw cycles on cryolesion size were
      studied. The final shape of the cryolesion at 15-20 min freezing was cylindrical
      and its distal hemispherical end extended 8 mm beyond the tip of the cryoprobe.
      The rate of increase in maximum diameter was logarithmic and decreased from 4.7
      mm/min during the first 5 min to 0.4 mm/min during the fourth 5-min period of
      freezing. By contrast, the rate of increase in volume was linear and ranged from
      9.6 to 7.9 ml/min during the corresponding periods. The volume of the hepatic
      cryolesion after 20 min of continuous freezing was significantly greater than
      that of the cryolesion formed with 20 min of cumulative freezing interrupted by a
      5-min spontaneous thaw. The ultimate temperatures reached and the cooling rates
      varied in different zones within the cryolesion depending on distances away from
      and alongside the cryoprobe. Diameter measurements taken in isolation do not
      reflect the actual growth rate of the cryolesion. Volume measurements define more
      accurately the amount of tissue frozen and left in situ. Prolonged freezing
      beyond 20 min did not increase the diameter of the cryolesion. A single
      continuous freeze produces a larger cryolesion than two freeze-thaw cycles of the
      same freezing duration.

PMID- 9527876
TI  - Multiple digit formation in Xenopus limb bud recombinants.
AB  - We prepared recombinant limb buds of Xenopus tadpoles by grafting a mesenchyme
      mass of the hindlimb bud. The Xenopus recombinant limb buds with dissociated and
      reaggregated mesenchyme developed more than 30 digits with cartilage
      segmentation, while those with undissociated mesenchyme developed a limb with
      normal cartilage pattern. Before the formation of multiple digits, a patchy
      expression pattern of fgf-8, an AER marker, was observed in the distal region of
      recombinant limb buds. shh, a ZPA (zone of polarizing activity) marker, was
      expressed broadly in the distal region of recombinants. Recombinant limb buds
      with the reaggregated mesenchyme of anterior halves formed anterior digits with
      claws, and those with the mesenchyme of posterior halves formed posterior digits
      without claws. The temporal and spatial changes in the potency of multiple digit
      formation are discussed with reference to the regenerative capacity of Xenopus
      limb buds.

PMID- 9527877
TI  - Local inhibitory action of BMPs and their relationships with activators in
      feather formation: implications for periodic patterning.
AB  - The formation of periodic patterns is fundamental in biology. Theoretical models
      describing these phenomena have been proposed for feather patterning; however, no
      molecular candidates have been identified. Here we show that the feather tract is
      initiated by a continuous stripe of Shh, Fgf-4, and Ptc expression in the
      epithelium, which then segregates into discrete feather primordia that are more
      strongly Shh and Fgf-4 positive. The primordia also become Bmp-2 and Bmp-4
      positive. Bead-mediated delivery of BMPs inhibits local feather formation in
      contrast with the activators, SHH and FGF-4, which induce feather formation. Both
      FGF-4 and SHH induce local expression of Bmp-4, while BMP-4 suppresses local
      expression of both. FGF-4 also induces Shh. Based on these findings, we propose a
      model that involves (1) homogeneously distributed global activators that define
      the field, (2) a position-dependent activator of competence that propagates
      across the field, and (3) local activators and inhibitors triggered in sites of
      individual primordia that act in a reaction-diffusion mechanism. A computer
      simulation model for feather pattern formation is also presented.

PMID- 9527878
TI  - Ovotestes in B6-XXSxr sex-reversed mice.
AB  - The sex-reversed mutation Sxr results in XX males. In the absence of any other
      mutations, testis differentiation in XXSxr fetuses is essentially normal and only
      one report of an XXSxr fetus with ovotestes is in the literature. We report that
      84% (21/25) of 13 days postcoitum XXSxr fetuses on the B6 inbred genomic
      background have ovotestes. Ovotestes were found in fetuses from both Sxra and
      Sxrb variants. Examination of fetuses older than 13 dpc suggests that the
      presence of ovotestes is transient in most fetuses. However, one overt
      hermaphrodite was identified after birth. The development of ovotestes is
      associated with the inbred background and is exacerbated by the dominant spotting
      oncogene allele KitW-42J. We propose that spreading of X-inactivation into the
      Sxr region resulting in loss of Sry expression is more extensive in B6-Sxr
      strains.

PMID- 9527879
TI  - Morphological diversity of the avian foot is related with the pattern of msx gene
      expression in the developing autopod.
AB  - The formation of the digits in amniota embryos is accompanied by apoptotic cell
      death of the interdigital mesoderm triggered through BMP signaling. Differences
      in the intensity of this apoptotic process account for the establishment of the
      different morphological types of feet observed in amniota (i.e., free-digits,
      webbed digits, lobulated digits). The molecular basis accounting for the
      differential pattern of interdigital cell death remains uncertain since the
      reduction of cell death in species with webbed digits is not accompanied by a
      parallel reduction in the pattern of expression of bmp genes in the interdigital
      regions. In this study we show that the duck interdigital web mesoderm exhibits
      an attenuated response to both BMP-induced apoptosis and TGFbeta-induced
      chondrogenesis in comparison with species with free digits. The attenuated
      response to these signals is accompanied by a reduced pattern of expression of
      msx-1 and msx-2 genes. Local application of FGF in the duck interdigit expands
      the domain of msx-2 expression but not the domain of msx-1 expression. This
      change in the expression of msx-2 is followed by a parallel increase in
      spontaneous and exogenous BMP-induced interdigital cell death, while the
      chondrogenic response to TGFbetas is unchanged. The regression of AER, as deduced
      by the pattern of extinction of fgf-8 expression, takes place in a similar
      fashion in the chick and duck regardless of the differences in interdigital cell
      death and msx gene expression. Implantation of BMP-beads in the distal limb
      mesoderm induces AER regression in both the chick and duck. This finding suggests
      an additional role for BMPs in the physiological regression of the AER. It is
      proposed that the formation of webbed vs free-digit feet in amniota results from
      a premature differentiation of the interdigital mesoderm into connective tissue
      caused by a reduced expression of msx genes in the developing autopod.

PMID- 9527880
TI  - Multiple roles of the eyes absent gene in Drosophila.
AB  - The eyes absent (eya) gene plays an essential role in the events that lead to
      formation of the Drosophila eye; without expression of eya in retinal progenitor
      cells, they undergo programmed cell death just prior to the morphogenetic furrow,
      leading to an eyeless or reduced eye phenotype. The eya gene has recently been
      found to be highly conserved to humans, defining a new gene family. Insights into
      the gene's function in the fly, therefore, are likely to be relevant to the role
      of its homologs in vertebrates. Detailed studies at the subcellular level
      indicate that the Eya protein is localized to the nucleoplasm, suggesting a role
      in control of nuclear events. The eya gene shows expression and roles in tissues
      other than the eye, including subsets of cells of the adult visual system, brain,
      and ovary, as well as an elaborate expression pattern in the embryo. Various
      mutations in the eya gene cause loss of ocelli, female sterility, or lethality.
      Analysis of the embryonic lethal phenotype indicates that mutant alleles show
      defects in head morphogenesis. These data indicate that eya has critical roles in
      morphogenesis of a number of tissues in the animal, in addition to its role in
      early eye formation. Despite multiple roles at multiple stages of development of
      the fly, both the type I and type II forms of the protein, when expressed
      ectopically during larval development, can direct eye formation.

PMID- 9527881
TI  - Absence of PS integrins or laminin A affects extracellular adhesion, but not
      intracellular assembly, of hemiadherens and neuromuscular junctions in Drosophila
      embryos.
AB  - We have examined the role of integrins in the formation of the cell junctions
      that connect muscles to epidermis (muscle attachments) and muscles to neurons
      (neuromuscular junctions). To this end we have analyzed muscle attachments and
      neuromuscular junctions ultrastructurally in single or double mutant Drosophila
      embryos lacking PS1 integrin (alphaPS1betaPS), PS2 integrin (alphaPS2betaPS),
      and/or their potential extracellular ligand laminin A. At the muscle attachments
      PS integrins are essential for the adhesion of hemiadherens junctions (HAJs) to
      extracellular matrix, but not for their intracellular link to the cytoskeleton.
      The PS2 integrin is only expressed in the muscles, but it is essential for the
      adhesion of muscle and epidermal HAJs to electron dense extracellular matrix. It
      is also required for adhesion of muscle HAJs to a less electron dense form of
      extracellular matrix, the basement membrane. The PS1 integrin is expressed in
      epidermal cells and can mediate adhesion of the epidermal HAJs to the basement
      membrane. The ligands involved in adhesion mediated by both PS integrins seem
      distinct because adhesion mediated by PS1 appears to require the extracellular
      matrix component laminin A, while adhesion mediated by PS2 integrin does not. At
      neuromuscular junctions the formation of functional synapses occurs normally in
      embryos lacking PS integrins and/or laminin A, but the extent of contact between
      neuronal and muscle surfaces is altered significantly. We suggest that
      neuromuscular contact in part requires basement membrane adhesion to the general
      muscle surface, and this form of adhesion is completely abolished in the absence
      of laminin A.

PMID- 9527882
TI  - Coexpression of a constitutively active plasma membrane calcium pump with GFP
      identifies roles for intracellular calcium in controlling cell sorting during
      morphogenesis in Dictyostelium.
AB  - To examine the potential role of calcium in regulating Dictyostelium development,
      we reduced free cytosolic and total cell Ca2+ in Dictyostelium cells by
      expressing a constitutively active form of a human erythrocyte plasma membrane
      calcium pump. The pump-expressing cells lacked a thapsigargin-mediated increase
      in cytoplasmic calcium, consistent with a reduced level of total cellular Ca2+.
      During aggregation, the cells initially formed a large number of aggregation
      centers, many of which coalesced to form mounds that were smaller than those of
      wild-type cells, and the cells did not exhibit the normal formation of elongated
      aggregation streams. The majority of the mounds either arrested at this stage
      with the formation of small protrusions or formed very aberrant finger-like
      structures, indicating an essential role for cellular calcium in morphogenesis.
      We used pump and wild-type cells differentially labeled by expressing different
      wavelength (green and blue) forms of green fluorescent protein and three
      dimensional (3-D) reconstruction of serial fluorescent imaging to visualize the
      movement of pump and wild-type cells within the aggregate. The results showed
      that the pump cells exhibited very aberrant cell movement and sorting within the
      forming mound, suggesting that the reduced cytosolic calcium affects movement
      required for tip formation. When allowed to form chimeric organisms with wild
      type cells, pump cells preferentially localized to two bands, one at the
      prestalk/prespore boundary and the other in the very posterior of the organism,
      suggesting that pump cells are unable to properly sort. Expression of the calcium
      pump had little effect on the induction of prestalk- or prespore-specific genes,
      whereas extended treatment with EGTA blocked induction of both classes of cell
      type-specific genes. Our results suggest a role for intracellular Ca2+ in
      controlling cell sorting and morphogenesis in Dictyostelium.

PMID- 9527883
TI  - Matrix metalloproteinase inhibitors disrupt spicule formation by primary
      mesenchyme cells in the sea urchin embryo.
AB  - The primary mesenchyme cells of the sea urchin embryo construct an elaborate
      calcareous endoskeletal spicule beginning at gastrulation. This process begins by
      ingression of prospective primary mesenchyme cells into the blastocoel, after
      which they migrate and then fuse to form a syncytium. Skeleton deposition occurs
      in spaces enclosed by the cytoplasmic cables between the cell bodies. Experiments
      are described which probe the role of proteases in these early events of spicule
      formation and their role in the continued elaboration of the spicule during later
      stages of embryogenesis. We find that several inhibitors of metalloproteinases
      inhibit the continuation of spiculogenesis, an effect first reported by Roe et
      al. (Exp. Cell Res. 181, 542-550, 1989). A detailed study of one of these
      inhibitors, BB-94, shows that fusion of primary mesenchyme cells still occurs in
      the presence of the inhibitor and the formation of the first calcite granule is
      not impeded. Continued elaboration of the spicule, however, is completely
      stopped; addition of the inhibitor during the active elongation of the spicule
      stops further elongation immediately. Removal of the inhibitor allows resumption
      of spicule growth. The inhibition is accompanied by almost complete cessation of
      massive Ca ion transport via the primary mesenchyme cells to the spicule. The
      inhibitor does not prevent the continued synthesis of several spicule matrix
      proteins. Electron microscopic examination of inhibited primary mesenchyme cells
      shows an accumulation of characteristic vesicles in the cytoplasm. Gel zymography
      demonstrates that although most proteases in homogenates of primary mesenchyme
      cells are not sensitive to the inhibitor in vitro, a protease of low abundance
      detectable in the medium of cultured primary mesenchyme cells is inhibited by BB
      94. We propose that the inhibitor is interfering with the delivery of
      precipitated calcium carbonate and matrix proteins to the site(s) of spicule
      growth.

PMID- 9527884
TI  - Expression of a constitutively active type I BMP receptor using a retroviral
      vector promotes the development of adrenergic cells in neural crest cultures.
AB  - Previous work has demonstrated that the bone morphogenetic proteins (BMP)-2, BMP
      4, and BMP-7 can promote the development of tyrosine hydroxylase (TH)-positive
      and catecholamine-positive cells in quail trunk neural crest cultures. In the
      present work, we showed that mRNA for the type I bone morphogenetic protein
      receptor IA (BMPR-IA) was present in neural crest cells grown in the absence or
      presence of BMP-4. We have used a replication-competent avian retrovirus to
      express a constitutively active form of BMPR-IA in neural crest cells in culture.
      Cultures grown in the absence of BMP-4 and infected with retrovirus containing a
      construct encoding this activated BMPR-IA developed five times more TH
      immunoreactive and catecholamine-positive cells than uninfected control cultures
      or cultures infected with virus bearing the wild-type BMPR-IA cDNA. The number of
      TH-positive cells which developed was dependent on the concentration of virus
      bearing the activated receptor cDNA used in the experiments. Most TH-positive
      cells which developed also contained viral p19 protein. Total cell number was not
      affected by infection with the virus containing the activated receptor construct.
      The effect of the activated receptor was phenotype-specific since infection with
      the virus bearing the activated receptor cDNA did not alter the number or
      morphology of microtubule-associated protein (MAP)2-immunoreactive cells, which
      are distinct from the TH-positive cell population. These findings are consistent
      with the observation that MAP2-positive cells are not affected by the presence of
      BMP-4. Taken together, these results suggest that activity of BMPR-IA is an
      important element in promoting the development of the adrenergic phenotype in
      neural crest cultures.

PMID- 9527885
TI  - Bone morphogenetic proteins induce apoptosis and growth factor dependence of
      cultured sympathoadrenal progenitor cells.
AB  - Neuron numbers in developing vertebrate organisms are regulated by the
      availability of growth factors which promote their survival. However, neuron
      survival may also be regulated by growth factors which promote rather than
      prevent cell death. This study examined the effects of bone morphogenetic
      proteins (BMPs) in inducing apoptosis of MAH cells, an immortalized
      sympathoadrenal progenitor cell line. Treatment of MAH cells with BMP2 or BMP4
      killed the cells in a dose-dependent manner. By contrast, treatment with BMP7 or
      TGFbeta1 failed to affect survival, suggesting that induction of apoptosis is
      specific to the dpp subgroup of BMPs. Survival after treatment with BMP2 or BMP4
      required addition of fibroblast growth factor (FGF) and nerve growth factor
      (NGF), indicating that BMP treatment made the neurons dependent upon an exogenous
      factor for survival. Several experimental observations suggested an apoptotic
      mechanism for BMP-induced death. After BMP2 treatment, the cells progressively
      shrank and became pyknotic. Further, there was prominent endonucleosomic cleavage
      of DNA (laddering) as well as TUNEL staining. Moreover, BMP-induced death was
      inhibited by the caspase inhibitor z-VAD and was partially prevented by the
      endonuclease inhibitor aurintricarboxylic acid. These observations suggest that
      neuron numbers may be regulated by factors which promote death and that exposure
      to such factors may be a signal for the development of dependence upon other
      growth factors for survival.

PMID- 9527886
TI  - Ciliary neurotrophic factor stimulates astroglial hypertrophy in vivo and in
      vitro.
AB  - After insult or trauma, astrocytes become activated and endeavor to restore the
      brain's delicately balanced microenvironment. An index of their activated state
      is that they become enlarged or hypertrophic. Ciliary neurotrophic factor (CNTF),
      a member of the alpha helical family of cytokines, is synthesized by astrocytes
      and is generally regarded to be an autocrine and paracrine injury signal. To
      determine whether CNTF might be an endogenous signal that stimulates astrocyte
      hypertrophy in vivo, we intracerebrally injected 200 ng of recombinant human CNTF
      into the adult rat neocortex. To study the astrocytes their cytosol was stained
      with antibodies against S100beta and their nuclei were stained with propidium
      iodide (PI). Fluorescent images of astrocytic nuclei and somas were acquired
      using a confocal laser-scanning microscope and their areas were measured using
      the NIH image software. Within 24 h of treatment, CNTF induced a volume increase
      of the somas and nuclei of protoplasmic and fibrous astrocytes in vivo, and this
      effect persisted for at least 48 h. To determine whether CNTF activates
      astrocytes directly, glial cultures were treated with CNTF (10 ng/ml) and were
      evaluated by measuring the area of PI stained nuclei. CNTF stimulation increased
      the size of both polygonal and process-bearing astroglia. Since our studies in
      vivo have shown that CNTF induces other key aspects of gliosis (S. W. Levison et
      al., 1996; Exp. Neurol. 141, 256), we conclude that CNTF is a powerful activator
      of astrocytes and that it is likely responsible for the persistent glial
      hypertrophy observed following injuries and diseases of the CNS.

PMID- 9527887
TI  - Neuron-specific transduction in the rat septohippocampal or nigrostriatal pathway
      by recombinant adeno-associated virus vectors.
AB  - Viral vector-mediated gene transfer in brain can provide a means for gene therapy
      and functional studies. However, robust and persistent transgene expression in
      specific populations of the adult brain has been difficult to achieve. In an
      attempt to produce localized and persistent transduction in rat brain, we
      compared recombinant adeno-associated virus (rAAV) vectors incorporating either
      the immediate early cytomegalovirus (CMV) promoter or the neuron-specific enolase
      (NSE) promoter. Transduction in hippocampus resulting from the NSE promoter
      containing construct was more efficient and persistent than that resulting from
      the CMV promoter-containing construct. Most hippocampal cells transduced with the
      NSE promoter had multipolar neuron morphology. Neurons with glutamatergic
      morphology were transduced weakly. In order to produce a local supply of
      neurotrophic factor to cells that degenerate under certain disease and
      experimental conditions, the NSE promoter was utilized to drive expression of
      brain-derived neurotrophic factor (BDNF) in medial septum or substantia nigra. In
      this construct, the NSE promoter drives dicistronic expression of BDNF and an
      enhanced version of green fluorescent protein (GFP). We estimated 3000-15,000 GFP
      positive cells per injection of rAAV into septum or substantia nigra, a
      transduction ratio of 5-20 infectious virus particles per transduced cell. This
      frequency may be sufficient for trophic factor gene therapy as well as for
      investigating specific protein function in "topical (i.e., localized) transgenic"
      animals produced by rAAV.

PMID- 9527888
TI  - Induction of calcitonin gene-related peptide-like immunoreactivity in hippocampal
      neurons following ischemia: a putative regional modulator of the CNS
      injury/immune response.
AB  - Calcitonin gene-related peptide (CGRP) is a potent vasodilator and immune cell
      modulator. In two studies within the hippocampal formation (HF), CGRP-like
      immunoreactivity (CGRP-LI) was increased in the inner molecular layer of the
      dentate gyrus after adrenalectomy and in mossy cells after colchicine-induced
      destruction of granule neurons. Given the increase in CGRP-LI following damage to
      the granule cell region of the HF, we investigated another trauma model,
      ischemia, that targeted different areas of the HF, CA1 region, and subiculum to
      ascertain the regional expression of this peptide after insult. Following
      ischemia, light microscopic evaluation showed CGRP-LI in basket cell-like
      neuronal perikarya within the dorsal subiculum and CA1 region of the hippocampus
      and in varicose fibers within the CA2 region of the hippocampus. Control rats
      rarely expressed CGRP-LI within neurons in these regions. In ischemic brains,
      double-labeled immunocytochemistry with antibodies to various neural markers
      demonstrated co-localization of CGRP-LI primarily within surviving subicular and
      CA1 cells resembling interneurons containing parvalbumin-LI or calbindin-LI.
      Electron microscopic analysis of the CA1 region from ischemic brains showed that
      CGRP-LI was contained in terminals with numerous small synaptic vesicles that
      formed symmetric synapses with perikarya and large dendrites of pyramidal cells,
      some of which were degenerating. Collectively, the data from this study and our
      previous study indicate that damage induces CGRP-LI expression in interneurons
      and nonprincipal cells in the area of damage, and we hypothesize that CGRP
      expression in surviving neurons within damage-related regions of the hippocampus
      is likely to be an important, and possibly a protective, component of the
      response of the nervous system to injury.

PMID- 9527889
TI  - Heme oxygenase in the experimental ALS mouse.
AB  - Heme oxygenase-1 (HO-1) is a stress protein inducible in some cells by oxidative
      stress. The status of heme oxygenase was investigated in a transgenic mouse model
      of amyotrophic lateral sclerosis (ALS) since oxidative mechanisms are postulated
      in neuronal injury. Three ALS mice [(SOD1-G93A)1Gur] and three controls [(SOD
      1)2Gur] were obtained from The Jackson Laboratory. Behavioral differences
      suggestive of neurodegeneration in ALS mice developed at 4-5 months of age. All
      mice were killed at 7-8 months of age. Tissue vacuolation, cell loss, and the
      presence of GFAP+ cells were noted in the spinal cords of ALS mice. Spinal cord
      motor neurons in both control and ALS mice stained positive for heme oxygenase-2
      (HO-2). While not precluding the presence of low levels of HO-1 neither
      immunohistochemical staining nor Western blot analysis provided evidence for
      significant HO-1 induction in degenerating spinal cord.

PMID- 9527890
TI  - Huntingtin protein colocalizes with lesions of neurodegenerative diseases: An
      investigation in Huntington's, Alzheimer's, and Pick's diseases.
AB  - Huntington's disease (HD) is an autosomal dominant neurodegenerative disease
      associated with a CAG trinucleotide repeat expansion in a large gene on
      chromosome 4. The gene encodes the protein huntingtin with a polyglutamine tract
      encoded by the CAG repeat at the N-terminus. The number of CAG repeats in HD are
      significantly increased (36 to 120+) compared with the normal population (8-39).
      The pathological mechanism associated with the expanded CAG repeat in HD is not
      clear but there is evidence that polyglutamine is directly neurotoxic. We have
      immunolocalized huntingtin with an in-house, well-characterised, polyclonal
      antibody in HD, Alzheimer's disease (AD), and Picks disease (PiD) brains. Control
      brain tissue sections were from head injured and cerebral ischaemia cases. In HD,
      huntingtin was immunopositive in the surviving but damaged neurons and reactive
      astrocytes of the caudate and putamen. However, in AD and PiD the immunostaining
      was largely restricted to the characteristic intracellular inclusion bodies
      associated with the disease process in each case. In AD, huntingtin was localized
      only in the intracellular neurofibrillary tangles and dystrophic neurites within
      the neuritic amyloid plaques but not with the amyloid. In PiD, strongly positive
      huntingtin immunostaining was present within cytoplasmic Pick bodies. Our
      findings suggest huntingtin selectively accumulates in association with abnormal
      intracytoplasmic and cytoskeletal filaments of neurons and glia in
      neurodegenerative diseases such as HD, AD, and PiD. Cells in the CNS appear
      sensitive to damage by the aggregated, toxic levels of huntingtin and evidence of
      its interaction with neurofilaments could provide information about its potential
      role in the aetiology of HD.

PMID- 9527892
TI  - Temporal cortex synaptophysin mRNA is reduced in Alzheimer's disease and is
      negatively correlated with the severity of dementia.
AB  - We measured synaptophysin mRNA in neocortical tissue from 7 prospectively
      assessed, pathologically verified normal individuals, 17 subjects with
      Alzheimer's disease (AD), and 13 subjects with a non-AD dementia. In temporal
      cortex (Brodmann area 21), synaptophysin mRNA was decreased in AD and non-AD
      dementia groups compared to controls. The loss was also present relative to
      polyadenylated mRNA content. Synaptophysin mRNA signal correlated negatively with
      the degree of dementia and negatively with the pathological severity of AD. In
      occipital cortex (Brodmann area 17) there were no differences between groups nor
      clinicopathological correlations. These data extend the evidence for a regional
      synaptic pathology in AD which affects synaptic protein gene expression by
      temporal cortex neurons.

PMID- 9527891
TI  - Topographical organization of opioid peptide precursor gene expression following
      repeated apomorphine treatment in the 6-hydroxydopamine-lesioned rat.
AB  - Many studies have previously described changes in preproenkephalin-A (PPE-A) and
      preproenkephalin-B (PPE-B) gene expression in the striatum of the 6
      hydroxydopamine (6-OHDA)-lesioned rat model of Parkinson's disease (both with or
      without dopamine replacement treatment). To date, these studies have either taken
      the striatum as a whole or have focused on a single subregion of the striatum.
      However, the striatum is organized into anatomically discrete parallel circuits
      serving different functions (motor, associative, and limbic). We have therefore
      employed in situ hybridization to examine the detailed topography of changes in
      opioid precursor expression following dopamine depletion and subsequent treatment
      with apomorphine (5 mg/kg twice daily for 10 days). In the untreated 6-OHDA
      lesioned striatum PPE-A expression was elevated only in the dorsal (sensorimotor)
      caudate-putamen. Following apomorphine treatment PPE-A mRNA levels were further
      raised in the sensorimotor striatum (</=77%) and approximately doubled and
      tripled in the ventral caudate-putamen (associative) and nucleus accumbens
      (limbic), respectively. These subsequent elevations were mostly restricted to
      rostral portions of the striatum. Although unchanged following vehicle treatment,
      PPE-B gene expression in the lesioned caudate-putamen (sensorimotor and
      associative) was elevated some 30-fold by apomorphine treatment. A smaller rise
      (fivefold) was seen in rostral regions of the lesioned nucleus accumbens. Thus,
      differential regulation of opioid peptide transmission exists in motor, limbic,
      and associative regions of the striatum and may contribute to the generation of
      motor and cognitive disturbances following long-term treatment of the dopamine
      depleted striatum.

PMID- 9527893
TI  - Neuronal cyclin expression in the hippocampus in temporal lobe epilepsy.
AB  - This study used immunocytochemistry to explore the expression of cyclins A, B, D,
      and E and the apoptosis-associated Bax protein in hippocampal subfields of 35
      lobectomy specimens with medial temporal lobe sclerosis removed for the treatment
      of temporal lobe epilepsy (TLE), 2 age-matched controls, and 2 elderly patients
      suffering from drug-responsive epilepsy. Cyclins A and D were not detected at all
      in neuronal nuclei. Cyclin E was only rarely detected in neuronal nuclei in drug
      controlled and TLE groups and in controls. Cyclin B was expressed in
      significantly more neuronal nuclei in the hippocampi in TLE than in the other
      groups studied. The nuclear expression of these proteins suggested that neurons
      had reentered the cell division cycle and reached the G2 phase. The nuclear
      expression of cyclin B in the hippocampus from these patients was accompanied by
      neuronal cytoplasmic expression of the death-related Bax protein. We interpret
      these neuronal findings as evidence of cell cycle disturbances and a possible
      apoptotic mechanism of hippocampal neuronal cell death in TLE.

PMID- 9527895
TI  - Selective inhibition of early axonal regeneration by myelin-associated
      glycoprotein.
AB  - When the distal stump of a transected peripheral nerve is brought into the
      vicinity of the proximal nerve stump, the regenerating axons advance toward it
      across the gap. Similar results are obtained when a predegenerated nerve segment
      is used. However, when a nerve segment subjected to proximal axotomy 7 days
      earlier (7-day nerve segment) was placed close to the proximal end of a freshly
      cut nerve at a distance of less than 1.5 mm, there were neither regenerating
      axons nor sprouts. The same inhibition of axonal regeneration was also exhibited
      when a nerve segment subjected to axotomy 9 to 14 days earlier was used. To
      examine the inhibitory effect of the nerve segments on established regenerating
      axons, we positioned a 7-day nerve segment in close apposition to a proximal
      nerve end at 2 or 3 days after transection. The growth of the 3-day-old
      regenerating axons, already ensheathed by Schwann cells, was not disturbed, but
      the 2-day-old regenerating axons, consisting of naked axons, were eliminated by
      the 7-day nerve segment. It is assumed that the findings reflect a mechanism
      serving to eliminate abundant sprouts and immature axons, probably conferring
      optimum regeneration and maturation of outgrowing pioneer axons. The inhibitory
      effect on abundant sprouts and immature axons was completely blocked by local
      application of antibodies to myelin-associated glycoprotein (MAG). The MAG
      containing cells appeared at 6 to 12 days after axotomy.

PMID- 9527894
TI  - Olfactory disorder in motor neuron disease.
AB  - In Parkinson's disease and Alzheimer's disease there is profound disorder of
      olfaction. The extent to which this modality is involved in motor neuron disease
      (MND) has been studied little. To address this further we assessed olfaction by
      three methods-a smell identification test ("UPSIT") in 58 patients and 135
      controls; olfactory-evoked response (OEP) to H2S in 15 patients, and pathological
      examination of olfactory bulbs obtained from 8 cadavers. It was found that smell
      identification compared with the controls was slightly worse overall in the MND
      group as a whole, but only the bulbar patients scored significantly less on the
      UPSIT. Patients displayed a subtle defect in cheese odor recognition. OEPs were
      normal in 9 subjects and delayed in 1 subject. The remaining 5 OEPs were
      unsuccessful. Histopathological studies of olfactory bulbs showed excess
      lipofuscin deposition in all 8 cases examined, indicating subclinical neuronal
      damage. Olfactory neurons with a degree of antioxidant defect may be more
      susceptible to cellular damage than other neuronal groups because of their direct
      relationship to environmental agents. Overall we found the degree of olfactory
      dysfunction in MND to be mild and in contrast with the marked changes described
      by others.

PMID- 9527896
TI  - Toxicity of dieldrin for dopaminergic neurons in mesencephalic cultures.
AB  - Dieldrin can be retained for decades in lipid-rich tissue and has been measured
      in some postmortem PD brains. Dieldrin has been reported to deplete brain
      monoamines in several species and has been shown to inhibit mitochondrial
      respiration. To further investigate the possibility that it may be involved in
      the pathogenesis of parkinsonism, its toxicity for dopaminergic (DA) neurons was
      assessed in a mesencephalic cell culture model. Primary neuronal cultures of
      mesencephalic neurons were prepared from fetal rats or fetal mice, grown for 1
      week and incubated with Dieldrin (0.01-100 microM) for 24 or 48 h. Toxicity for
      DA neurons was determined by measuring density of surviving tyrosine hydroxylase
      immunoreactive (TH-ir) cells. Toxicity for gamma-aminobutyric acid (GABA)-ergic
      neurons was determined by measuring survival of glutamate decarboxylase (GAD)-ir
      neurons. General, nonselective cytotoxicity was determined by counting cells
      visualized by phase contrast microscopy or by DAPI-stained cells with
      fluorescence microscopy. Dieldrin exposure for 24 h resulted in a dose-dependent
      decrease in survival of TH-IR cells (DA neurons) with a 50% decrease (EC50)
      produced by 12 microM in rat mesencephalic cultures. Dieldrin also produced a
      dose- and time-dependent decrease in mouse DA-ergic and GABA-ergic neurons in
      mouse mesencephalic cultures. GABA-ergic neurons were less sensitive to the toxin
      compared to DA-ergic neurons. Cellular uptake of 3H-DA was also affected by lower
      concentrations of Dieldrin (EC50 = 7.98 microM) than uptake of 3H-GABA (EC50 = 43
      microM). Thus, Dieldrin appears to be a relatively selective DA-ergic neurotoxin
      in mesencephalic cultures. Dieldrin, which may be ubiquitous in the environment,
      is proposed as an agent which can initiate and promote dopaminergic
      neurodegeneration in susceptible individuals.

PMID- 9527897
TI  - MRI-stereotactical approach for neural grafting in basal ganglia disorders.
AB  - Optimization of the procedures for neural grafting is a timely issue, as this
      technique has proven beneficial for a few patients with late-stage Parkinson's
      disease in pilot studies and therefore may expand to become a more widely
      available therapeutic. In this research, one major issue is that of the placement
      of the cell deposits in the right target areas within the striatum. Although it
      is widely accepted that these suitable regions are the sensorimotor regions of
      the putamen, reliable delineation of these areas using classical stereotactical
      mapping techniques remains difficult. Along the course of a 5-year-long clinical
      transplantation program, we have developed an original procedure based on
      magnetic resonance imaging of the striatum on parasagittal views. This technique
      allowed us to identify precisely, and reproducibly in each patient, three
      subregions of the putamen (precommissural, commissural, and postcommissural) to
      be implanted. On the basis of the literature defining the sensorimotor putaminal
      regions in nonhuman primates, it was subsequently possible to extrapolate and
      localize these regions in each patient, thus providing a basis for the placement
      of cell deposits. Examples taken from our series of grafted patients demonstrate
      the value of this procedure that, in addition, minimizes interference of
      interindividual variability in the interpretation of clinical results.

PMID- 9527898
TI  - Expression of MHC class I and beta2-microglobulin in rat spinal motoneurons:
      regulatory influences by IFN-gamma and axotomy.
AB  - The low expression of MHC antigens is believed to be one factor of importance
      contributing to the immune-privileged status of CNS neurons. We here describe
      that motoneurons, in contrast to other nerve cells in the lumbar spinal cord of
      the adult rat, express both MHC class I and beta2-microglobulin mRNA. The
      motoneurons also display in situ hybridization signal for IFN-gamma receptor
      mRNA. After a peripheral axotomy, the motoneurons show a clear upregulation of
      beta2-microglobulin mRNA. IFN-gamma treatment of cultured rat embryonic spinal
      motoneurons causes a similar upregulation of especially beta2-microglobulin.
      Based on these facts, we propose that spinal motoneurons can be influenced by IFN
      gamma and recognized by cytotoxic CD8+ T-cells. These findings could be of
      relevance in the search for pathogenetic mechanisms in motoneuron-specific
      diseases, such as ALS.

PMID- 9527899
TI  - Early amyloid deposition in the medial temporal lobe of young Down syndrome
      patients: a regional quantitative analysis.
AB  - The presence of the neuropathological alterations of Alzheimer's disease (AD) in
      essentially all older Down syndrome (DS) patients suggests that the examination
      of younger DS patients may clarify the early pathological progression of AD. We
      examined the hippocampus and parahippocampal-inferior temporal gyri of 42 DS
      patients (ages 4 days to 38 years) for the deposition of amyloid beta protein
      (Abeta) using both a modified Bielschowsky stain and immunohistochemistry for
      Abeta protein. The parahippocampal and inferior temporal gyri demonstrated Abeta
      staining in cases as young as 8 years of age. As age and degree of Abeta
      deposition increased, staining included the CA-1/subiculum and dentate molecular
      layer followed then by the remainder of the CA hippocampal regions. The first
      neuritic plaques were observed in the CA-1/subiculum, despite this being a later
      region of Abeta deposition. Although Abeta staining increased with age, there was
      substantial variability in the severity of Abeta deposition within age groups.
      These results suggest that within the hippocampal/parahippocampal region there is
      a progressive stereotypic deposition of Abeta. The variable severity of Abeta
      deposition within age groups suggests that other factors, besides DS, may be
      contributing to the timing and severity of Abeta deposition.

PMID- 9527900
TI  - Chronic administration of quinolinic acid in the rat striatum causes spatial
      learning deficits in a radial arm water maze task.
AB  - Chronic intrastriatal administration of quinolinic acid (QA) in the rat produces
      a pattern of neurodegeneration similar to that seen in Huntington's disease (HD).
      Although these changes have been related to transient motor abnormalities, the
      effects of chronic QA administration on cognitive abilities have not been
      assessed. The present study investigated whether the striatal deterioration
      observed during chronic QA administration produces cognitive impairments in this
      animal model of HD by testing the effects of chronic administration of QA on
      spatial learning ability of rats in a radial arm water maze (RAWM) task. Rats
      were given bilateral implantation of a chronic dialysis probe apparatus which
      delivered either vehicle or QA (20 mM) into the striatum. Beginning 1 day after
      implantation, the rats were tested daily for 3 weeks in the RAWM. Nocturnal
      activity levels were also assessed at 1-, 3-, 5-, 7-, 14-, and 21-days following
      probe implantation. Results of behavioral testing indicated that chronic exposure
      to QA causes spatial learning deficits in the RAWM task with only a transient
      increase in activity levels. Collectively, these results suggest that chronic
      striatal exposure to QA mimics some aspects of the cognitive deficits observed in
      HD.

PMID- 9527901
TI  - NGF depletion reduces ipsilateral and contralateral trigeminal satellite cell
      reactions after inferior alveolar nerve injury in adult rats.
AB  - Following peripheral nerve injury, neuronal cell functions in sensory ganglia
      shift from normal maintenance and neurotransmission toward survival and
      regeneration. A rapid modulation of glial cell activity, which is related to
      changes in neuronal-support cell interaction, also occurs after nerve injury.
      Nerve growth factor (NGF) is required for the survival and maintenance of
      specific populations of sensory and sympathetic neurons, and changes in neuronal
      gene expression after axonal injury are due in part to a loss of NGF retrograde
      transport from the periphery to the cell body. A similar role for NGF in
      modulating support cell responses to peripheral nerve injury, however, has not
      been demonstrated. Using an autoimmune model, we assessed the effects of NGF
      depletion in adult rats on the injury-induced expression of glial fibrillary acid
      protein immunoreactivity (GFAP-IR) in the ipsilateral and contralateral
      trigeminal ganglia (TG). Unilateral inferior alveolar nerve crush resulted in a
      bilateral, NGF-dependent trigeminal satellite cell response. In control rats
      there was a widespread induction of GFAP-IR in the ipsilateral as well as the
      contralateral TG. In contrast, GFAP-IR was reduced to the mandibular division of
      the ipsilateral TG in NGF-depleted rats, and the contralateral up-regulation of
      GFAP-IR was entirely abolished. Bilateral sympathectomy failed to mimic the
      effects of autoimmunization. Our results provide evidence that NGF depletion
      inhibits injury-induced satellite cell responses, independent of its effects on
      sympathetic nerve function.

PMID- 9527903
TI  - Selective loss of alpha motoneurons innervating the medial gastrocnemius muscle
      in a mouse model of amyotrophic lateral sclerosis.
AB  - Mutations in the superoxide dismutase gene 1 (SOD-1) are found in patients with
      familial amyotrophic lateral sclerosis (FALS). Overexpression of a mutated human
      SOD-1 gene in mice results in neurodegenerative disease as result of motoneuron
      loss in lumbar spinal cord (10). Using this mouse model of FALS, we have
      established a quantitative assay utilizing the retrograde tracer Fluorogold (FG)
      to determine the number of motoneurons innervating one skeletal muscle in mice
      with ongoing disease. In adult wild-type mice, the number of alpha motoneurons
      retrogradely labeled by an injection of FG into medial gastrocnemius muscle is 50
      +/- 7 and this number remains constant from 7 to 18 weeks of age. In mutant mice,
      the number of alpha motoneurons retrogradely labeled by FG is the same as in wild
      type mice at 7 and 9 weeks, but then declines to 36% of that in normal mice at 18
      weeks. This decline also correlates positively to severity of motor impairments
      in these mice as assessed by the hindlimb splay test. In contrast, the number of
      FG-labeled gamma motoneurons remains relatively unchanged in both wild-type and
      mutant mice up to 18 weeks. At 18 weeks of age, this apparent alpha motoneuron
      denervation is paralleled by an average of 55% reduction of MG-muscle mass and
      40% weaker performance in the hindlimb splay test. These data suggest that alpha
      motoneurons are the most vulnerable neuronal subtype in this mouse model of ALS
      and it is primarily their loss that leads to functional motor deficits. This
      quantitative bioassay also will be valuable for evaluating novel therapeutics for
      ALS.

PMID- 9527902
TI  - Diffusion- and T2-weighted increases in magnetic resonance images of immature
      brain during hypoxia-ischemia: transient reversal posthypoxia.
AB  - Hypoxic-ischemic changes in brain are detected earlier with diffusion-weighted
      (DW) than with T2-weighted magnetic resonance (MR) imaging techniques in adults,
      whereas the response in immature brain is not known. We investigated MR imaging
      changes prior to, during, and/or after 2 h of hypoxia-ischemia (right carotid
      artery occlusion + 2 h of hypoxia) in 7-day-old rats anesthetized with
      isoflurane. In general, within the first 45 min of hypoxia-ischemia there were no
      changes in the DW or T2-weighted images. By the second hour of hypoxia-ischemia
      there were marked areas of increased intensity in both the T2 and the DW images,
      with cortex and striatum being affected prior to thalamus and hippocampus. The
      area of DW exceeded that of T2 hyperintensities. In the first hour after hypoxia
      ischemia there was a transient recovery of hyperintensities on both T2 and DW
      images. Between 24 and 72 h the hyperintense area on DW images decreased, whereas
      that on T2-weighted images increased. The distribution of pathological damage
      assessed histologically correlated with the areas of hyperintensity on the MR
      images. In contrast to adult brain, early hypoxic-ischemic injury in immature
      brain is detected as an increase in intensity in both diffusion- and T2-weighted
      images, indicating a unique alteration in brain water dynamics in this neonatal
      model of hypoxia-ischemia. These imaging changes and alterations in brain water
      can rapidly but transiently reverse upon the start of normoxia and reperfusion,
      suggestive of secondary energy failure or delayed neuronal death.

PMID- 9527904
TI  - Failure to detect cytotoxic T cell activity against recombinant Yo protein using
      autologous dendritic cells as the target in a patient with paraneoplastic
      cerebellar degeneration and anti-Yo antibody.
AB  - Paraneoplastic neurological syndromes are believed to be autoimmune neuronal
      degenerations that develop in some patients with systemic cancer. Although a high
      titer of anti-Yo antibody has been found in the sera and cerebrospinal fluid of
      patients with paraneoplastic cerebellar degeneration (PCD), the role of anti-Yo
      antibody in Purkinje cell loss has not been shown. Previously we found that all
      of nine Japanese patients with PCD who harbored anti-Yo antibody had HLA A24. In
      this present study we have examined cytotoxic T cell (CTL) activity against
      recombinant Yo protein in peripheral blood of a patient with PCD and anti-Yo
      antibody using autologous dendritic cells as the target. We did not detect CTL
      activity against Yo protein, though, this study does not exclude the possibility
      of the involvement of CTL in the development of PCD.

PMID- 9527905
TI  - Diorthosubstituted polychlorinated biphenyls in caudate nucleus in Parkinson's
      disease.
AB  - As it had previously been demonstrated that there were reduced brain dopamine
      concentrations in monkeys who had been given polychlorinated biphenyls (PCBs)
      chronically, we hypothesized that organochlorine compounds in general, and PCBs
      in particular, might be important in the pathogenesis of Parkinson's disease
      (PD). In a study of caudate nucleus obtained post mortem from patients with
      Parkinson's disease and from controls, there were significantly higher
      concentrations of the organochlorine insecticide dieldrin and the PCB congener
      153 in the PD tissue. DDE, PCB congener 180, and total PCBs (matched with a
      commercial preparation) also tended to be higher in Parkinson's disease tissue.
      We think that this is important preliminary evidence that diorthosubstituted PCBs
      may contribute to the pathogenesis of Parkinson's disease, and a greater presence
      of organochlorine insecticides in the PD tissue suggests that this may be in part
      the explanation for the association between PD and rural living.

PMID- 9527907
TI  - Meeting announcement 
AB  - Copyright

PMID- 9527906
TI  - Further on Einstein's brain.

PMID- 9527908
TI  - Announcement 
AB  - Copyright

PMID- 9527909
TI  - Volume 8, Number 2 (1997): Kyung-Eui Ro, Carl S. Keener, and Bruce A. McPheron,
      "Molecular Phylogenetic Study of the Ranunculaceae: Utility of the Nuclear 26S
      Ribosomal DNA in Inferring Intrafamilial Relationships," pp. 117-127:
AB  - Copyright

PMID- 9527910
TI  - Demonstration of the specificity of poliovirus encapsidation using a novel
      replicon which encodes enzymatically active firefly luciferase.
AB  - The specificity of poliovirus encapsidation has been studied using a novel
      chimeric genome in which the gene encoding firefly luciferase has been
      substituted for the VP2-VP3-VP1 genes of the poliovirus capsid (P1) gene.
      Transfection of RNA transcribed in vitro from this genome resulted in a VP4
      luciferase fusion protein which retained luciferase enzyme activity. Since the
      detection of enzyme activity was dependent upon replication of the transfected
      RNA genome, we refer to these genomes as replicons. The replicon encoding
      luciferase was encapsidated upon transfection of the genomic RNA into cells
      previously infected with a recombinant vaccinia virus, VV-P1, which encodes the
      poliovirus type 1 capsid proteins (P1). Infection of cells with each serial
      passage, followed by analysis of luciferase enzyme activity, revealed that
      encapsidated replicons could be detected at the first passage with VV-P1.
      Amplification of the titer of encapsidated replicons occurred upon serial passage
      with VV-P1, as evidenced by the high expression levels of luciferase enzyme
      activity following infection. Serial passage of the luciferase replicons with
      poliovirus type 1, 2, or 3 resulted in the trans encapsidation into the type 1,
      2, or 3 capsids, respectively. In contrast, serial passage with bovine
      enterovirus, Coxsackievirus A21 or B3, or enterovirus 70 did not result in trans
      encapsidation, even though co-infection of cells with the replicon and different
      enteroviruses resulted in high-level expression of luciferase. The results of
      this study highlight the specificity of poliovirus encapsidation and point to the
      use of encapsidated replicons encoding luciferase as a reagent for dissecting
      elements of replication and encapsidation.

PMID- 9527911
TI  - Selective quasispecies transmission after systemic or mucosal exposure of
      macaques to simian immunodeficiency virus.
AB  - Sexual transmission is the major cause of the AIDS epidemic. For the development
      of new antiviral and vaccine strategies, we therefore need to understand the
      mechanisms by which lentiviruses cross the mucosal barrier and the subsequent
      pathogenic consequences. For this purpose, experimental approaches are greatly
      facilitated by the development of relevant animal models. In this study, macaques
      were inoculated intravenously, intrarectally, or intravaginally with a pathogenic
      cell-free isolate of SIVmac251. Patterns of virological and immunological events
      significantly differed between vaginally (transient viremia, late seroconversion)
      and intravenously or intrarectally inoculated monkeys (persistent viremia and
      early seroconversion). Two weeks after infection, analysis of the env gene
      nucleotide sequences of proviruses recovered from PBMCs demonstrated that most of
      the differences were observed in the V1 loop. Three viral variants were
      specifically associated with vaginal transmission, whereas no such selection was
      evidenced after intravenous or intrarectal transmissions. These results are in
      favor of specific mechanisms associated with vaginal transmission, implicating
      viral envelope structure.

PMID- 9527913
TI  - Genetic analysis of the UL 15 gene locus for the putative terminase of herpes
      simplex virus type 1.
AB  - The herpes simplex virus (HSV-1) UL15 gene encodes one of the six viral gene
      products required for viral DNA cleavage and packaging. UL15 is a spliced gene
      and encodes two separately translated proteins, UL15 and UL15.5. Sequence
      analysis reveals that UL15 shares homology with gp 17, the large catalytic
      subunit of the bacteriophage T4 terminase, a protein which cleaves the polymeric
      T4 DNA into monomers. Both proteins contain a putative ATP binding motif known as
      the Walker A and B boxes. In this report, immunofluorescence was used to show
      that UL15 localizes to the nucleus in the absence of any other viral proteins;
      this indicates that UL15 contains its own nuclear localization signal. In
      addition, we found that UL15 colocalizes with replication compartments at early
      times (6 h postinfection). Since, at this time, preformed capsids as well as
      other cleavage and packaging proteins are also recruited to replication
      compartments, it seems likely that cleavage and packaging occurs in the same
      compartments in which DNA synthesis occurs. Also in this report, we have
      investigated UL15.5, the N-terminally truncated gene product of the UL15 open
      reading frame (ORF). The start codon has been mapped to Met443 within the UL15
      ORF. Furthermore, we have shown that plasmids containing a UL15.5 knockout
      mutation still complement the growth of UL15 insertion mutant viruses, indicating
      that UL15.5 is not required for viral growth in cell culture. Last, we
      constructed a UL15 mutant, UL15C(G263A), in which the invariant Gly263 in the
      Walker box A of the ATP binding motif (GKT) was substituted with an alanine. We
      show that the mutant gene fails to support the growth of UL15 insertion mutant
      viruses, indicating that the putative ATP binding motif of UL15 is indispensable
      for its function.

PMID- 9527912
TI  - The role of leucine residues in the structure and function of a leucine zipper
      peptide inhibitor of paramyxovirus (NDV) fusion.
AB  - To investigate the molecular mechanisms involved in paramyxovirus-induced cell
      fusion, the function and structure of synthetic peptide analogs of the sequence
      from the leucine zipper region (heptad repeat region 2) of the Newcastle disease
      virus fusion protein (F) were characterized. As previously reported (Young et
      al., Virology, 238, 291), a peptide with the sequence ALDKLEESNSKLDKVNVKLT (amino
      acids 478-497 of the F protein) inhibited syncytia formation after transfection
      of Cos cells with the hemagglutinin-neuraminidase and F protein cDNAs. A peptide
      analog which had an alanine residue in place of the first leucine residue in the
      zipper motif (ALDKAEESNSKLDKVNVKLT) retained inhibitory activity but less than
      the original peptide. Further loss in activity was observed in a peptide in which
      two of the leucine residues were replaced with alanine (ALDKAEESNSKADKVNVKLT),
      and a peptide which had all leucine residues in the zipper motif replaced with
      alanine (ALDKAEESNSKADKVNVKLT) had no inhibitory activity. The three-dimensional
      conformations of these peptides in aqueous solution were determined through the
      use of nuclear magnetic spectroscopy and molecular modeling. Results showed that
      while the wild-type peptide formed a helix with properties between an alpha-helix
      and a 3(10) helix with leucine residues aligned along one face of the helix,
      progressive substitution of leucine residues with alanine resulted in the
      progressive loss of helical structure. The results suggest that alterations of
      leucine residues in the zipper motif disrupt secondary structure of the peptide
      and that this structure is critical to the inhibitory activity of the peptide.

PMID- 9527914
TI  - The hepatitis B virus e antigen cannot pass the murine placenta efficiently and
      does not induce CTL immune tolerance in H-2b mice in utero.
AB  - The function of the secretory core gene product (HBeAg) of the human hepatitis B
      virus is unclear. It has been discussed that this protein may be passed from the
      mother to the fetus, where it might induce immunologic tolerance. Here we have
      examined this possibility with transgenic mice expressing high levels of HBeAg.
      Analysis of serum samples obtained from nontransgenic fetuses which developed in
      HBeAg-positive mothers showed no evidence that the HBeAg can pass the placenta.
      Moreover, direct examination of the HBeAg- and HBcAg-specific cytotoxic T-cell
      immune response of H-2b mice which developed in either transgenic or
      nontransgenic mothers revealed no indication that mice which could have been
      exposed to the HBeAg in utero become tolerant to HBV core gene products. From
      these data we conclude that the placenta represents an efficient barrier for
      HBeAg transfer and that the HBeAg does not tolerize cytotoxic T cells, at least
      in mice of the H-2b haplotype.

PMID- 9527915
TI  - Nucleotide sequence analysis shows that Rhopalosiphum padi virus is a member of a
      novel group of insect-infecting RNA viruses.
AB  - Rhopalosiphum padi virus (RhPV) is an aphid virus that has been considered a
      member of the Picornaviridae based on physicochemical properties. The 10,011-nt
      polyadenylated RNA genome of RhPV was completely sequenced. Analysis of the
      sequence revealed the presence of two open reading frames (ORFs). The predicted
      amino acid sequence of ORF1, representing the first 6600 nt of the RhPV genome,
      showed significant similarity to the nonstructural proteins of several plant and
      animal RNA viruses. Direct sequence analysis of the RhPV capsid proteins showed
      that ORF2, which represents the last 2900 nt, encodes the three structural
      proteins (28, 29, and 30 kDa). The predicted amino acid sequence of ORF2 is very
      similar to the corresponding regions of Drosophila C virus, Plautia stali
      intestine virus, and to a partial sequence from the 3' end of the cricket
      paralysis virus genome. The site of initiation of protein synthesis for ORF2
      could not be determined from the amino acid and nucleotide sequences. ORF1 is
      preceded by 579 nt of noncoding RNA and the two ORFs are separated by more than
      500 nt of noncoding RNA. Like picornaviruses, these regions may function to
      facilitate the cap-independent initiation of translation of the two ORFs. These
      data suggest that RhPV, Drosophila C virus, Plautia stali intestine virus, and
      probably cricket paralysis virus are members of a unique group of small RNA
      viruses that infect primarily insects.

PMID- 9527916
TI  - The significance of the 3'-nontranslated region and E2 amino acid mutations in
      the virulence of Semliki Forest virus in mice.
AB  - We have recently shown that the 3'-nontranslated region (3'-NTR) of the avirulent
      Semliki Forest virus A7(74) [SFVA7(74)] contains a unique sequence of 101
      nucleotides and five repetitive nucleotide units whereas the 3'-NTR of the
      neurovirulent SFV4 has only two repeats. A chimeric virus was constructed by
      replacing the entire 3'-NTR of the SFV4 clone with the A7(74) 3'-NTR. The hybrid
      replicated efficiently in the central nervous system (CNS) of adult Balb/c mice
      and, similarly to SFV4, led to high mortality after intraperitoneal inoculation.
      In contrast, another chimeric virus, CME2, containing the E2 gene of the
      avirulent SFVA7(74) virus in the SFV4 clone was recently shown to be avirulent
      for mice. Several derivatives with single-site or a constellation of amino acid
      mutations were constructed. Two single-site E2 mutants, Val37lle and Asn212Ser,
      displayed an attenuated phenotype in mice with mortality reduced from 90 to 48
      and 43%, respectively. None of the multiple site mutants were significantly
      attenuated. Adult female mice showed a greater resistance to SFV infection than
      male mice. The SFV hybrid viruses, CM3NTR and CME2, reached the CNS similarly to
      the parental viruses, but the single-site E2 mutants were only sporadically found
      in the CNS. We conclude that in mice the 3'-NTR does not play a significant role
      in the pathogenesis of Semliki Forest virus and that specific E2 amino acid
      mutations reduce the virulence, especially in female mice. The results
      additionally suggest that individual amino acid mutations in the E2 glycoprotein
      affect the efficiency of migration into the CNS.

PMID- 9527917
TI  - Identification and characterization of virus assembly intermediate complexes in
      HIV-1-infected CD4+ T cells.
AB  - For type-C and lentiviruses, including human immunodeficiency virus type 1 (HIV
      1), the pathway of virus assembly remains poorly defined, and the assembly and
      budding of capsids are believed to occur simultaneously at the plasma membrane of
      the infected cell. We have now identified two putative HIV-1 assembly
      intermediate complexes in infected CD4+ T cells. The first of these
      intermediates, a detergent-resistant complex (DRC), was identified as a large
      oligomer that had a density of 1.10-1.13 g/ml and was primarily composed of
      Pr55Gag and Pr160Gag-Pol precursors. The other putative intermediate was a
      detergent-sensitive complex (DSC) with a density of 1.15-1.17 g/ml, which
      apparently represented the products of extensive proteolytic processing of both
      the Pr55Gag and Pr160Gag-Pol precursors. Both complexes could be distinguished
      from released mature virions as well as immature viral particles. Surprisingly,
      the formation of DRC was not dependent upon the myristylation at the N-terminus
      of the Gag proteins, a signal required for plasma membrane targeting and virus
      production. However, the myristic acid modification was essential for the
      formation of DSC. These data suggest that interactions between individual Gag
      molecules and between Gag and Gag-Pol precursors may occur before their targeting
      to the plasma membrane during HIV-1 assembly. However, formation of the late
      virus assembly complex and productive processing of Pr55Gag and Pr160Gag-Pol
      precursors apparently do not occur until these precursors are targeted to the
      plasma membrane.

PMID- 9527918
TI  - Activation of BLV transcription by NF-kappa B and Tax.
AB  - Bovine leukemia virus (BLV) is the causative agent of bovine leukosis, a
      naturally occurring fatal disease in cattle. BLV transcription is regulated by
      cellular transcription factors and the virally encoded oncoprotein Tax. In this
      report, we investigated the functional role of the putative NF-kappa B binding
      site recently identified in the BLV promoter. Our studies indicate that the kappa
      B binding motif acts as a functional enhancer in the presence of the cellular NF
      kappa B proteins. Furthermore, the kappa B site together with a single 21-bp
      repeat confers strong activation of BLV transcription in the presence the NF
      kappa B proteins and Tax. These results suggest that cellular NF-kappa B may be
      involved in the regulation of BLV transcription and activation of the virus from
      latency.

PMID- 9527919
TI  - Development of a chimeric sindbis virus with enhanced per Os infection of Aedes
      aegypti.
AB  - The TE/3'2J double subgenomic Sindbis (dsSIN) viruses have been used to stably
      express genes in Aedes aegypti nerve and salivary gland tissues. However, because
      these viruses inefficiently infect Ae. aegypti when administered by the per os
      route, TE/3'2J viruses must be intrathoracically inoculated into the mosquitoes
      to infect these tissues. A Malaysian Sindbis (SIN) virus isolate (MRE16) does
      efficiently infect Ae. aegypti midgut tissues after ingestion, and approximately
      95% of these mosquitoes also develop disseminated infections within 14 days. We
      have sequenced the entire 26S RNA of MRE16 virus and have developed a chimeric
      SIN cDNA infectious clone, designated MRE1001, which contains sequence elements
      of TE/3'2J and MRE16 virus. MRE1001 virus efficiently infects midgut cells, and
      greater than 90% of infected mosquitoes develop disseminated infections after 14
      days extrinsic incubation. The chimeric MRE1001 cDNA clone should allow
      identification of viral determinants of midgut infection and dissemination and
      lead to the development of new SIN virus expression systems.

PMID- 9527920
TI  - Crystallization and preliminary X-ray analysis of the dsDNA bacteriophage HK97
      mature empty capsid.
AB  - HK97 is a temperate dsDNA bacteriophage of Escherichia coli that is structurally
      similar to phage lambda, with an icosahedral head of triangulation (7) number 7.
      Although the capsids of several large dsDNA phages have been studied extensively
      using a variety of biophysical approaches, no high-resolution structure is
      available. We have grown crystals of mature but empty bacteriophage HK97 capsids
      that diffract to at least 3.5 A using synchrotron radiation. The HK97 Head II
      crystals are the first capsid crystals from a dsDNA bacteriophage that diffract X
      rays to high resolution. A capsid precursor (prohead) was made in vivo by
      expressing capsid proteins in E. coli. This prohead was purified, converted to
      Head II in vitro, and used to grow crystals. The empty Head II has the same form
      as the mature HK97 capsid, but without DNA. The crystals were grown in a mixture
      of ammonium sulfate and PEG 8000, directly in an X-ray capillary to minimize
      crystal handling. The unit cell is monoclinic, with dimensions a = 580 A, b = 625
      A, c = 790 A, beta = 90.0 degrees and two particles per unit cell.

PMID- 9527921
TI  - Organization of the cis-acting element required for wheat dwarf geminivirus DNA
      replication and visualization of a rep protein-DNA complex.
AB  - Initiation of geminivirus DNA replication depends on the activity of the
      initiator protein (Rep) upon interaction with DNA sequences present in the
      intergenic region of the viral DNA. In this study, we have analyzed the DNA
      sequences present in the large intergenic region (LIR) of wheat dwarf virus
      (WDV), a subgroup I member of the geminivirus family, which are required for
      viral DNA replication. We have (i) defined the boundaries of the viral cis-acting
      DNA replication element, (ii) determined the contribution of different domains of
      the LIR to DNA replication efficiency, and (iii) visualized WDV Rep-DNA
      complexes. Analysis of unidirectional deletions from both sides of the LIR leads
      us to establish that a approximately 200-bp cis-acting element (core) is
      essential for viral DNA replication. It spans approximately 170 and 28 bp
      upstream and downstream, respectively, from the initiation site (+1), located in
      the invariant loop. This core element is flanked, at each side, by auxiliary
      regions (5'-aux and 3'-aux, approximately 70 and approximately 25 bp long,
      respectively), which contain DNA sequences that stimulate DNA replication.
      Competition experiments using viral replicating vectors bearing wild-type or
      mutant WDV LIRs suggest that the auxiliary regions may contribute to the
      stabilization and/or activity of the initiation complex formed by WDV Rep at the
      origin. We have visualized DNA-protein complexes by electron microscopy and a
      high-affinity binding site of WDV Rep protein within the core element has been
      mapped to approximately 144 +/- 18 bp upstream from the initiation site, between
      the start site for complementary-sense transcription and the TATA box. Our
      studies (i) establish the modular structure of the WDV DNA replication cis-acting
      element and (ii) provide direct evidence for the formation in vitro of a large
      nucleoprotein complex within the essential cis-acting element.

PMID- 9527922
TI  - Evidence for the separate regulation of the human papillomavirus type 11 E7 and
      E6 promoters by Viral cis sequences near the E6 promoter.
AB  - The human papillomavirus type 11 (HPV-11) E7 protein can modulate host cell
      functions and is required for papilloma formation, but little is known concerning
      the regulation of its expression. This study was designed to determine whether
      the viral upstream regulatory region controlled expression from the E7 promoter
      and whether cis sequences differentially regulated E6 and E7 expression in
      laryngeal mucosal keratinocytes, the natural target cells for this virus.
      Reporter constructs were designed to study expression of the luciferase gene from
      the HPV-11 E7 promoter in its natural position downstream of a functional E6
      promoter. E7 expression, like E6 expression, required upstream regulatory
      sequences. However, E7 expression was less sensitive to repression by viral E2
      protein and to mutation of the Spl binding site adjacent to the E2 binding site.
      Moreover, there was differential sensitivity of the two promoters to mutation of
      the E6 TATA box, with E7 expression more affected than E6 expression. These
      findings show that, in the normal host cells for this virus, the E6 and E7
      promoters can be independently regulated by the cis regulatory region adjacent to
      the E6 promoter.

PMID- 9527924
TI  - Feline infectious peritonitis viruses arise by mutation from endemic feline
      enteric coronaviruses.
AB  - Feline infectious peritonitis virus (FIPV) strains from six cats and three
      different geographic areas were compared genetically with feline enteric
      coronavirus (FECV) isolates obtained from cats inhabiting the same environments.
      Sequence comparisons were made from 1.2- to 8.9-kb segments on the 3' end of the
      genome. FECV/FIPV pairs from the same catteries or shelters were 97.3-99.5%
      related but were genetically distinct from FIPV and FECV strains obtained from
      cats living in geographically distinct environments. The high genetic similarity
      between FECVs and FIPVs from the same environment strongly suggested a common
      ancestry. Based on the presence of deletion mutations in the FIPVs and not in the
      FECVs, it was concluded that FIPVs evolved as mutants of FECVs. The mutations are
      deletions in the FIPVs and not insertions in the FECVs since similar sequences
      are present in other strains that have segregated earlier from a common ancestor.
      Therefore, the order of descent is form FECV to FIPV. Mutations unique to FIPVs
      were found in open reading frames (ORFs) 3c in 4 of 6 isolates and/or 7b in 3 of
      6 isolates. When the study was extended to include 7 additional FIPV isolates,
      11/13 of the FIPVs sequenced were found to have mutated 3c ORFs.

PMID- 9527923
TI  - Atypical splicing of the latency-associated transcripts of herpes simplex type 1.
AB  - We previously have shown that two latency-associated transcripts (LATs) of herpes
      simplex type 1 (HSV-1) are probably lariats, produced during splicing. By RNaseH
      digestion analysis, we now show that the major branchpoint of the 2.0-kb LAT was
      within 46 nt 5' of the splice acceptor site. A more detailed mapping by primer
      extension revealed the branchpoint as an adenosine 29 nt 5' of the splice
      acceptor site. Introduction of two branchpoint sequences with good matches to the
      consensus at position -25 had no effect on the splicing efficiency but reduced
      the accumulation of the 2.0-kb LATs at least 90-fold. The second focus of our
      studies was the 1.5-kb LAT. It was not detected by Northern analyses in either
      productively infected or transfected cultured cells or even in cells of neuronal
      origin. However, it was detected in the trigeminal ganglia of mice experimentally
      infected with HSV-1 after 10 days. Moreover, its abundance relative to that of
      the 2.0-kb species increased 4-fold from 10 to 30 days after infection,
      consistent with an interpretation that the 1.5-kb species, once formed, was more
      stable than the 2.0-kb species.

PMID- 9527925
TI  - Stimulation of local immunity and protection in mice by intramuscular
      immunization with triple- or double-layered rotavirus particles and QS-21.
AB  - Based on studies in animal models, parenteral immunization has become recognized
      as a potential vaccination strategy against rotavirus. Using an adult mouse
      model, the effects of the saponin adjuvant QS-21 on protection against murine
      rotavirus (strain EDIM) infection was determined following two intramuscular
      (i.m.) immunizations with purified EDIM particles including triple-layered (tl)
      infectious particles, tl particles inactivated with psoralen/UV, and double
      layered (dl) inactivated particles. All three particles stimulated large serum
      rotavirus IgG responses and small amounts of serum rotavirus IgA, but
      undetectable stool rotavirus IgA. Inclusion of QS-21 during immunization
      increased the serum responses approximately 2- to 10-fold and also stimulated low
      levels of stool rotavirus IgA. Protection based on reduced shedding of rotavirus
      following EDIM challenge was significant (P < 0.001) with each immunized group
      and was enhanced (P < 0.001) by inclusion of QS-21 during immunization. Mice
      immunized with either live or inactivated tl particles and QS-21 were almost
      fully protected. Furthermore, animals inoculated with dl particles and the
      adjuvant shed significantly (P = .02) less virus following challenge than mice
      immunized with inactivated tl particles even though the latter induced measurable
      titers of neutralizing antibody to EDIM. These results demonstrate significant
      protection against rotavirus following i.m. immunization with both dl and tl EDIM
      particles which is consistently enhanced with QS-21.

PMID- 9527926
TI  - Actin binding and nucleation by Autographa california M nucleopolyhedrovirus.
AB  - The budded form of Autographa californica M nucleopolyhedrovirus enters
      permissive cells via adsorptive endocytosis. Shortly after nucleocapsid
      penetration into the cytoplasm, thick actin cables form, which frequently project
      toward the nucleus. These actin cables are transient structures, formed in
      association with viral nucleocapsids prior to viral gene expression and
      concomitant with nucleocapsid transport to the nucleus. In this paper we report
      that nucleocapsids are capable of nucleating actin polymerization in vitro in a
      concentration-dependent manner. Two viral-encoded capsid proteins, p39 and
      p78/83, were found to bind actin directly and therefore could be involved in the
      observed acceleration of actin polymerization. When nucleocapsids were added to
      actin in the presence of cytochalasin D, actin polymerization was reduced to
      levels below those obtained with actin and cytochalasin D alone, suggesting that
      the nucleocapsids bound to the pointed ends of actin filaments. Finally,
      treatment of infected cells with the myosin inhibitor 2,3-butanedione monoxime
      delayed nucleocapsid transport to the nucleus. We postulate that upon entering
      the cytoplasm, AcMNPV nucleocapsids induce the polymerization of actin cables,
      which, in conjunction with a myosin-like motor, facilitate their transport to
      and/or into the nucleus.

PMID- 9527927
TI  - Influence of mucosal and parenteral immunization with a replication-defective
      mutant of HSV-2 on immune responses and protection from genital challenge.
AB  - Herpes simplex virus (HSV) most frequently initiates infection at a mucosal
      surface; thus mucosal immune responses are likely to be important in defense
      against HSV infection. We have examined the effects of eliciting mucosal as well
      as systemic immune responses on protection against genital challenge infection
      with virulent HSV-2 in mice immunized with a replication-defective mutant of HSV
      2. In addition, we have examined the types of immune responses elicited by
      immunization by the different routes under conditions known to provide
      protection. We observed that immunizations at parenteral and distal mucosal sites
      generate immune responses that have an additive effect in protection against
      challenge infection with virulent HSV-2. Immunization at either of these sites
      alone prevented paralysis and death after challenge virus infection and reduced
      replication of the challenge virus in the genital mucosa, although subcutaneous
      immunization was more effective in reducing virus replication. Simultaneous
      immunization at the two sites led to the greatest reduction in mucosal
      replication of challenge virus. The type of response generated was also affected
      by the route of immunization. Subcutaneous immunization results in a strong
      systemic immune response that is somewhat biased toward a Th1 T cell response,
      while intranasal immunization induces mucosal as well as systemic immunity, as
      evidenced by HSV-specific IgA in vaginal secretions, and a stronger bias toward a
      Th1 response. These results suggest that mucosal immunization may complement
      protective immunity against HSV-2 genital infection generated by parenteral
      immunization with replication-defective mutant virus.

PMID- 9527928
TI  - Nuclear targeting activity associated with the amino terminal region of the Borna
      disease virus nucleoprotein.
AB  - The Borna disease virus (BDV) replicates in the nucleus. The viral p40 protein
      (N), which is found abundantly in the nucleus in BDV-infected cells, may play an
      important role in virus replication. To analyze the amino acid residues involved
      in the nuclear targeting of BDV N, a series of eukaryotic expression plasmids
      encoding deletion mutants of N was constructed and transfected into COS-7 cells.
      In indirect immunofluorescence assays with a rabbit anti-BDV N antiserum, wild
      type N was located in the nucleus of transfected cells in the absence of other
      viral constituents. In contrast, mutants lacking the 13 NH2-terminal amino acid
      residues 1MPPKRRLVDDADA13 in common gave a cytoplasmic localization pattern.
      Similarly, a mutant with substitution of 4KRR6 by 4NSG6 was retained in the
      cytoplasm. Furthermore, a nonapeptide, 3PKRRLVDDA11, derived from the NH2
      terminal region of N conferred nuclear targeting activity to beta-galactosidase,
      which normally resides in the cytoplasm. Thus, we have identified the nuclear
      targeting signal of the BDV N and narrowed it to the NH2-terminal region where
      4KRR6 basic amino acid residues are located.

PMID- 9527929
TI  - Characterizations of coronavirus cis-acting RNA elements and the transcription
      step affecting its transcription efficiency.
AB  - Seven to eight species of viral subgenomic mRNAs are produced in coronavirus
      infected cells. These mRNAs are produced in different quantities, and their molar
      ratios remain constant during viral replication. We studied RNA elements that
      affect coronavirus transcription efficiency by characterizing a series of cloned
      coronavirus mouse hepatitis virus (MHV) defective interfering (DI) RNAs
      containing an inserted intergenic sequence, from which subgenomic DI RNA is
      transcribed in MHV-infected cells. Certain combinations of upstream and
      downstream flanking sequences of the intergenic sequence suppressed subgenomic DI
      RNA transcription, yet changing one of the flanking sequences to a different
      sequence eliminated transcription suppression. The suppressive effect of certain
      combinations of flanking sequences, but not all combinations, could be
      counteracted by altering the intergenic sequence. Thus, the combination of
      intergenic sequence and flanking sequence affected transcription efficiency. We
      also characterized another set of DI RNAs designed to clarify which transcription
      step determines the relative molar ratios of coronavirus mRNAs. Our study
      indicated that if subgenomic mRNAs were exclusively synthesized from negative
      strand genomic RNA, then the relative molar ratios of coronavirus mRNAs were most
      likely determined after synthesis of the genomic-sized template RNA. If negative
      strand subgenomic RNAs were templates for subgenomic mRNAs, then the relative
      molar ratios of coronavirus mRNAs probably were determined after synthesis of the
      genomic-sized template RNA used for subgenomic-sized RNA transcription but prior
      to the completion of the synthesis of subgenomic-sized RNAs containing the leader
      sequence. The relative molar ratios of coronavirus mRNAs, therefore, seem to have
      been established prior to a putative replicon-type amplification of subgenomic
      mRNAs.

PMID- 9527931
TI  - Stoichiometry of reovirus structural proteins in virus, ISVP, and core particles.
AB  - All eight reovirus structural proteins were resolved in a new tris, glycine, and
      urea (TGU) electrophoretic gel system. The specific identities of proteins were
      determined immunologically, biochemically, and genetically. Structural proteins
      of reovirus type 1 Lang had different mobilities in the TGU gel than did type 3
      Dearing proteins. Intertypic reassortant viruses that contained various
      combinations of parental genes were used to identify each of the viral protein
      bands. Type 1 Lang virions were metabolically-labelled with either 3H-amino acids
      or 35S-methionine/cysteine and gradient purified. Aliquots of purified virions
      were treated to generate infectious subviral particles (ISVPs) and core
      particles. Radiolabelled virus, ISVP, and core proteins were resolved in the TGU
      gel and protein band intensities were used to determine copy numbers of each
      structural protein. These studies confirmed the copy numbers and locations of
      most reovirus proteins. However, important new findings include the discovery
      that virions contain approximately 120 copies of major core protein sigma 2 and
      20 copies of the polymerase cofactor protein mu 2, and ISVP particles contain
      about 24 copies of mu 1 C that has not been processed to the delta peptide. These
      data are used to generate a new model of the arrangement of structural proteins
      with the reovirus particle.

PMID- 9527932
TI  - Retroviral recombination is nonrandom and sequence dependent.
AB  - Sequence variation plays a significant role in the pathogenesis and persistence
      of retroviral infections and is a major obstacle in the development of vaccines
      as well as therapies against lethal diseases caused by retroviruses.
      Recombination is one means by which sequence variation is generated. However, the
      basic molecular mechanisms of recombination are not adequately understood. In the
      present study, a spleen necrosis virus (SNV) recombination system was used to ask
      whether a known hot spot for mutation was also a hot spot for retroviral
      recombination. The system consisted of a pair of SNV vectors expressing two drug
      resistance genes, constructed so that recombinants could be selected by a double
      resistant phenotype. Restriction enzyme site differences engineered into the
      vectors were used to map the location of recombination sites within relatively
      small intervals (55 to 420 bp). The vectors were modified to create two pairs
      that differed only by the presence of runs of identical nucleotides. The runs of
      identical nucleotides had been shown previously to be hot spots for frameshift
      mutations during SNV reverse transcription. Each vector pair was introduced into
      DSDh helper cells by infection. Viruses were harvested from doubly infected DSDh
      helper cells and used to infect D-17 target cells. Proviral sequences from 228
      cell clones were analyzed by polymerase chain reaction and restriction enzyme
      digestion. Significant differences in the patterns of recombination were found
      between the two pairs of vectors. In particular, the frequency of recombination
      was higher than expected in the interval immediately following the runs. For both
      pairs of vectors, the overall pattern of recombination was nonrandom and one
      region was refractory toward recombination.

PMID- 9527930
TI  - Reactivities of human sera with human herpesvirus-8-infected BCBL-1 cells and
      identification of HHV-8-specific proteins and glycoproteins and the encoding
      cDNAs.
AB  - The reactivates of human sera with uninduced and phorbol ester (TPA)-induced
      human herpesvirus-8 (HHV-8)-infected BCBL-1 cells were examined by
      immunofluorescence assay (IFA) and by radioimmunoprecipitation reactions (RIP).
      The seroprevalence of HHV-8 infections is low in the United States general
      population and only low levels of HHV-8 antibodies were detected in the
      seropositive sera. In contrast, high levels of antibodies against HHV-8 lytic and
      latent antigens were detected by IFA in the sera from HIV+ Kaposi's sarcoma (KS)
      positive individuals. These sera recognized several proteins and glycoproteins
      from BCBL-1 cells in RIP reactions. Two types of antibody responses were detected
      in the sera from HIV+ KS- homosexual men. In majority of the sera with and
      without detectable HHV-8 DNA in the peripheral blood mononuclear cells (PBMC),
      significantly low levels of HHV-8 antibodies were detected by IFA. These sera
      recognized only a subset of HHV-8 proteins and glycoproteins in RIP reactions. In
      contrast, in a subgroup of sera from HIV+ KS- homosexual men, higher levels of
      IFA antibodies against HHV-8 lytic and latent antigens were detected. These sera
      also recognized several viral proteins and glycoproteins in RIP reactions. These
      results suggest that antibody response profiles to HHV-8 infection vary
      significantly and serologic assays to detect antibody responses to a panel of
      both lytic and latent antibodies may be required for maximum sensitivity.
      Screening of a cDNA library from TPA-induced BCBL-1 cells with an HIV+ KS+ serum
      identified cDNAs encoding 12 HHV-8 proteins. Further characterization of these
      HHV-8 proteins would define the HHV-8 antigens useful for seroepidemiological
      studies and in discriminating lytic, latent, past, and/or reactivation
      infections.

PMID- 9527933
TI  - Function and Conformation of Wild-Type p53 Protein Are Influenced by Mutations in
      Bovine Leukemia Virus-Induced B-Cell Lymphosarcoma
AB  - The mutations of the p53 gene previously represented one of several genetic
      changes involved in the development of bovine leukemia virus (BLV)-induced
      lymphosarcoma, while the effects of these mutations on the function of p53 are
      unknown. We identified four mutations of p53 gene in BLV-infected cattle with
      lymphosarcoma and demonstrated clearly the existence of two functionally distinct
      groups of mutants: (i) the mutant forms with substitutions at codons 241 and 242,
      which were mapped within an evolutionally conserved region and corresponded to
      the human "hot-spot" mutations, had completely lost the capacities for
      transactivation and growth suppression and gained transdominant repression
      activity in p53-null SAOS-2 cells; and (ii) the mutations at codons 206 and 207
      were located outside the evolutionally conserved regions. These mutants partially
      retained the capacity for transactivation and growth suppression and failed to
      inhibit the transactivation activity of coexpressed wild-type p53, instead
      showing an enhancement of this activity. In addition, protein analysis using an
      antibody specific for the mutant form revealed that the mutations at codons 206
      and 242 induced a "mutant" conformation of the bovine p53 proteins. Collectively,
      these results show that mutations of p53 gene in BLV-infected cattle with
      lymphosarcoma can potentially alter its physiological function and may play an
      important role in BLV-induced leukemogenesis. Copyright 1998 Academic Press.

PMID- 9527934
TI  - Structure-function analysis of the herpes simplex virus type 1 UL12 gene:
      correlation of deoxyribonuclease activity in vitro with replication function.
AB  - Although the product of the UL12 gene of herpes simplex virus type 1 (HSV-1) has
      been shown to possess both exonuclease and endonuclease activities in vitro, and
      deletion of most of the gene within the viral genome results in inefficient
      production and maturation of infectious virions, the function of the
      deoxyribonuclease (DNase) activity per se in virus replication remains unclear.
      In order to correlate the in vitro and in vivo activities of the protein encoded
      by UL12, mutant proteins were tested for nuclease activity in vitro by a novel
      hypersensitivity cleavage assay and for their ability to complement the
      replication of a DNase null mutant, AN-1. Rabbit reticulocyte lysates programmed
      with wild-type UL12 RNA cleaved at the same sites cleaved by purified HSV-1
      DNase, but distinct from those cleaved by DNase 1 or micrococcal nuclease. All
      mutants which lacked DNase activity in vitro also failed to complement the
      replication of AN-1 in nonpermissive cells. Likewise, all mutants which contained
      HSV-1 DNase activity, as detected by the hypersensitivity cleavage assay, were
      capable of complementing the replication of the DNase null mutant, though to
      varying extents. Of particular note was the d1-126 mutant protein, which, despite
      having the same specific activity as the wild-type enzyme in vitro, complemented
      the replication of AN-1 significantly less than the wild-type protein. The
      results suggest that DNase activity per se is required for efficient replication
      of HSV-1 in vivo. However, residues, including the N-terminal 126 amino acids,
      which are dispensable for enzymatic activity in vitro may facilitate the
      accessibility or activity of the protein in vivo.

PMID- 9527935
TI  - Perinatology: a cooperative venture.

PMID- 9527936
TI  - Effect of increased environmental temperature on breathing patterns in preterm
      and term infants.
AB  - OBJECTIVE: This study was done to evaluate the effect of an increase in
      environmental temperature in healthy infants on breathing patterns during sleep.
      STUDY DESIGN: Ten preterm infants (mean gestational age 30.6 [SD 1.5] weeks) who
      reached maturity and 10 term comparison infants underwent polysomnographic
      studies before, during, and after exposure to raised environmental temperature.
      Core temperature and instances of central and obstructive apnea during active
      sleep and quiet sleep were recorded and compared between and within the two
      groups. RESULTS: At environmental temperatures between 29 degrees and 30 degrees
      C, both groups of infants had longer and more frequent apneic episodes than at 24
      degrees C. Compared with baseline findings, in preterm infants at a
      postconceptional age of 38 (SD 1) weeks, the apnea index increased during quiet
      sleep, whereas in term infants aged 36 to 72 hours (similar postconceptional
      age), an increased index was observed during active sleep. CONCLUSION: A mild
      increase in environmental temperature has an effect on breathing patterns in both
      preterm (even when they have reached maturity) and term infants. However, a
      different response related to sleep state was observed in the two groups. We
      speculate that these effects may play a role in the association between a life
      threatening event and elevated environmental temperature in both groups of
      infants.

PMID- 9527937
TI  - Does cesarean section decrease the incidence of major birth trauma?
AB  - OBJECTIVE: To determine whether the increase in frequency of cesarean section is
      associated with a decreased incidence of major birth trauma. STUDY DESIGN: A
      retrospective cohort study was performed evaluating all neonatal cases of major
      birth trauma from January 1989 to December 1994. Major birth trauma was defined
      as peripheral plexus or nerve injuries, fractures, or lacerations. The data were
      grouped into two mutually exclusive periods (January 1989 to December 1990 vs
      January 1991 to December 1994) in which a significant difference in the cesarean
      section rate was known. RESULTS: Of 17,957 deliveries during the period, 141
      cases of birth trauma occurred. One hundred thirty-seven of the 141 medical
      records were available for review, and 116 were classified as having had major
      birth trauma and were included in the study. The overall incidence of major birth
      trauma was 6.5/1000 deliveries. During the two-year period (January 1989 to
      December 1990), 18.3% of deliveries were by cesarean section and the major birth
      trauma rate was 8.4/1000 deliveries. During the following 4 years, the cesarean
      section rate was 22.3% and the major birth trauma rate was 5.3/1000 deliveries.
      Significant differences in the birth trauma chi(2) = 6.12, p = 0.013) and
      cesarean section (chi(2) = 40.80, p < 0.001) rates were observed. Controlling for
      the mode of delivery lessened the association between time period and birth
      trauma incidence (chi(2)MH = 3.28, p = 0.07). A significant decrease in the
      occurrence of major birth trauma in neonates delivered by cesarean section in the
      later period was discovered (relative risk = 0.46, 95% confidence interval 0.22
      to 0.97). This decrease appeared to be mediated by a decrease in total
      lacerations between the periods (chi(2) = 11.76, p < 0.001), because the rates of
      other types of major birth trauma did not differ in neonates delivered by
      cesarean section or the vaginal route. CONCLUSIONS: With a 4% increase in rate of
      cesarean section at our institution, a significant decrease in the occurrence of
      major birth trauma was observed. This finding cannot be explained by a decreased
      risk of neonatal trauma in patients delivering vaginally, but rather by a
      decreased risk of neonatal trauma at cesarean section during the latter period.

PMID- 9527938
TI  - Comparison of analgesics in ameliorating the pain of circumcision.
AB  - OBJECTIVE: Our objective was to compare two methods of pain control during
      neonatal circumcision: a sucrose-dipped pacifier and an analgesic cream (EMLA).
      STUDY DESIGN: This study was conducted in our well-baby nursery where 80 male
      infants were placed into one of four groups: control (water-dipped pacifier
      only), sucrose alone, EMLA alone, or sucrose and EMLA. Heart rate, oxygen
      saturation, systolic and diastolic blood pressure, and crying time were measured
      as indicators of pain. The primary data analysis was a 2 x 2 factorial analysis
      of variance with repeated measures. RESULTS: Physiologic and behavioral
      parameters indicated significantly (p < 0.05) decreased pain response in all
      treatment groups compared with that in the control group. The combination of
      sucrose and EMLA was most effective in reducing pain responses; sucrose alone was
      significantly less effective. There were no side effects of treatment.
      CONCLUSION: Pain during neonatal circumcision can be optimally ameliorated by
      combined use of a sucrose-dipped pacifier and a local analgesic cream.

PMID- 9527939
TI  - Neonatal hypoperistalsis associated with perinatal zidovudine administration.
AB  - OBJECTIVE: This paper presents the cases of two infants exposed to perinatal
      zidovudine in whom hypoperistalsis and intestinal pseudoobstruction developed.
      STUDY DESIGN: Clinical case reports were prepared of two infants born to women
      infected with human immunodeficiency virus who were treated with perinatal
      zidovudine at a single inner-city medical school. RESULTS: None of the previously
      described causes for this rare condition contributed to the symptoms in these two
      infants. In addition, the symptoms resolved shortly after discontinuation of
      zidovudine administration. CONCLUSIONS: Although a strict cause-and-effect
      relationship between the medication and the impairment in intestinal peristalsis
      was not proved, awareness of this association should be helpful for physicians
      caring for infants exposed to perinatal zidovudine.

PMID- 9527940
TI  - Comparison of intra-amniotic (15S)-15-methyl-PGF2 alpha and intravaginal
      prostaglandin E2 for second-trimester uterine evacuation.
AB  - OBJECTIVE: To compare the efficacy, safety, and side effects of intra-amniotic
      (15S)-15-methyl prostaglandin F2 alpha (15-M-PGF2 alpha) and intravaginal
      prostaglandin E2 (PGE2) for midtrimester uterine evacuation. STUDY DESIGN: Ninety
      three patients underwent therapeutic midtrimester pregnancy termination by the
      use of laminaria placement and intra-amniotic injection of 15-M-PGF2 alpha. A
      matched control group underwent uterine evacuation by laminaria placement and
      insertion of PGE2 intravaginal suppositories. The main outcomes studied were time
      to delivery, side effects, and complications. RESULTS: The 15-M-PGF2 alpha group
      had a shorter time to delivery (12.3 +/- 6.4 hours) compared with the PGE2 group
      (16.2 +/- 6.6 hours, p < 0.0001). The evacuation rate over time was significantly
      greater in the 15-M-PGF2 alpha group (p = 0.001). The PGE2 group had a
      significantly higher incidence of side effects. CONCLUSIONS: The use of intra
      amniotic 15-M-PGF2 alpha for therapeutic second-trimester pregnancy termination
      is safe and is associated with a more rapid evacuation of the uterus and fewer
      side effects than intravaginal PGF2 suppositories.

PMID- 9527942
TI  - Factors affecting humidity of inspired gas in a neonatal lung model.
AB  - OBJECTIVE: The American National Standards Institute recommends an absolute
      humidity of > or = 30 mg/L of inspired gas in patients receiving mechanical
      ventilation. This study was designed to assess the absolute humidity of inspired
      gas in relation to humidifier settings and environmental conditions in a test
      lung. STUDY DESIGN: Measurements were obtained at the endotracheal tube manifold
      of an artificial lung in an isolette or radiant warmer with use of a nonheated
      wired system and two different ventilator circuit lengths. Temperature and
      relative humidity were measured at three environmental temperatures and various
      humidifier settings. RESULTS: We achieved adequate absolute humidity levels only
      at near maximum humidifier settings. When the artificial lung was placed in an
      isolette with a standard circuit length inside the isolette, adequate absolute
      humidity was never reached at an environmental temperature of 30 degrees C.
      Increasing the length of the ventilator circuit situated inside the isolette or
      using a radiant warmer improved absolute humidity compared with that obtained
      with use of a standard circuit length. CONCLUSION: Recommended absolute humidity
      levels may not be reached at the manifold even at high humidifier settings. Thus
      actual measurements of relative humidity and temperature at the endotracheal tube
      site are necessary to optimize humidity according to American National Standards
      Institute recommendations.

PMID- 9527941
TI  - Microbiology of necrotizing fasciitis associated with omphalitis in the newborn
      infant.
AB  - OBJECTIVE: The purpose of this study was to report the aerobic and anaerobic
      microbiology of periumbilical necrotizing fasciitis in newborn infants. STUDY
      DESIGN: Retrospective review was done of the author's 20-year experience.
      RESULTS: Specimens obtained from 11 newborn infants with periumbilical
      necrotizing fasciitis were cultured for aerobic and anaerobic bacteria. A total
      of 38 bacterial isolates was recovered: 21 aerobic and facultative and 17
      anaerobic. Aerobic or facultative bacteria only were present in 1 specimen (9%),
      anaerobes only in 2 (18%), and mixed aerobic and anaerobic flora in 8 (73%).
      Multiple organisms were recovered from all instances and the number of isolates
      varied from two to six (average 3.5 isolates per specimen). The predominant
      isolates were Peptostreptococcus sp. (7 isolates); Bacteroides fragilis group
      (6); streptococcus group B (4); and Staphylococcus aureus, streptococcus group D,
      Escherichia coli, and Proteus mirabilis (3 each). All patients underwent
      extensive debridement and resection, and they received supportive and
      antimicrobial therapy. Six (55%) of the patients died. CONCLUSIONS: These
      findings illustrate the polymicrobial aerobic-anaerobic flora of periumbilical
      necrotizing fasciitis.

PMID- 9527944
TI  - Clinical utility of a bedside blood analyzer for measuring blood chemistry values
      in neonates.
AB  - OBJECTIVE: The purpose of this study was to determine whether blood chemistry
      measurements obtained by a bedside blood analyzer through an umbilical artery
      catheter agreed with those obtained with use of conventional laboratory
      analyzers. STUDY DESIGN: Forty-two neonates (1910 +/- 1000 gm) being treated in a
      level III neonatal intensive care unit had 88 blood samples drawn through an
      umbilical artery catheter. Serum sodium, potassium, glucose, and hematocrit
      concentrations were measured (n = 352) with use of a laboratory analyzer (0.7 ml
      of blood) and a bedside blood analyzer (0.06 ml of blood). RESULTS: Only 5.7% of
      all measurement differences (20/352) were outside the predetermined clinically
      acceptable difference range, and just 1.4% (5/352) might have affected clinical
      decision making. Correlations between laboratory analyzer measurements and
      bedside blood analyzer measurements were excellent: serum potassium, r = 0.97, p
      = 0.0001; serum glucose, r = 0.93, p = 0.0001; and blood hematocrit, r = 0.93, p
      = 0.0001. Serum sodium measurement correlation was significant (p = 0.0001) but
      weaker (r = 0.86). CONCLUSION: The bedside blood analyzer evaluated in this
      report is clinically useful for neonatal patients and could limit phlebotomy loss
      if used routinely.

PMID- 9527943
TI  - Effect of beta-blockade on symptomatic dexamethasone-induced hypertrophic
      obstructive cardiomyopathy in premature infants: three case reports and
      literature review.
AB  - OBJECTIVE: The objective of this study was to assess the efficacy of beta
      blockade on clinically significant left ventricular outflow tract obstruction in
      premature infants treated with dexamethasone because of bronchopulmonary
      dysplasia. STUDY DESIGN: Case reports are presented of three premature infants
      (mean gestational age 27 weeks) cared for in the intensive care nursery in whom
      clinically significant septal hypertrophy and left ventricular outflow tract
      obstruction developed during dexamethasone treatment for bronchopulmonary
      dysplasia. The infants were treated with oral propranolol. Serial physiologic and
      echocardiographic parameters were followed. Physiologic data were analyzed with
      an analysis of variance, with the Kruskal-Wallis test used for nonparametric
      data. A p value < 0.05 was considered statistically significant. RESULTS: Oral
      administration of the beta-blocker propranolol resulted in clinical and
      echocardiographic improvement of the left ventricular outflow tract obstruction.
      One patient had a lower average heart rate and two patients had lower average
      mean blood pressure values during propranolol treatment, none of which was
      clinically significant. None of the patients had worsening of the respiratory
      status. CONCLUSION: beta-blockade treatment was well tolerated and may be
      beneficial in relieving symptomatic steroid-induced left ventricular outflow
      tract obstruction in premature infants.

PMID- 9527946
TI  - Meconium aspiration syndrome: importance of the monitoring of labor.
AB  - OBJECTIVE: This study was conducted to identify the associated obstetric and
      neonatal factors in babies with meconium aspiration syndrome. STUDY DESIGN: All
      babies diagnosed with meconium aspiration were included in the study. Maternal
      details, monitoring of labor, and mode of delivery were recorded. The neonatal
      details included Apgar scores, resuscitation, weight, gestational age, and the
      grading of the radiographs for severity of meconium aspiration syndrome. Outcome
      was determined as survival or death, the need for mechanical ventilation, and the
      severity of the radiographic changes. RESULTS: Of the 55 patients entered into
      the study 8 babies (14.5%) died and 23 (42%) received mechanical ventilation.
      Fifty-four percent of the babies were born postterm. Univariate analysis revealed
      that the lack of monitoring of the labor was the most significant variable
      associated with moderate to severe radiographic changes (p = 0.008). Tracheal
      suction was significantly associated with more severe radiographic changes (p =
      0.008). One (8.2%) of 12 babies with mild radiographic changes had an arterial pH
      < 7.2 (p = 0.032). Multivariate analysis showed that mortality and the need for
      mechanical ventilation were associated with monitoring of labor and with
      prolonged resuscitation. Moderate to severe changes on radiograms were associated
      with tracheal suction and with prolonged resuscitation. The obstetric
      complications in this study were those commonly seen in the local obstetric
      practice. CONCLUSION: The monitoring of labor was the most significant factor in
      the reduction of meconium aspiration syndrome. The presence of more severe
      radiologic changes in those babies who had tracheal suction and a lower arterial
      pH supports the view that aspiration occurs in some babies before delivery. The
      number of babies delivered postterm suggests that avoidance of postmaturity is a
      further preventive factor in meconium aspiration syndrome.

PMID- 9527945
TI  - Two-hour postprandial test versus one-hour, fifty-gram glucola test as screening
      tools for gestational diabetes: a critical analysis.
AB  - OBJECTIVE: The objective of this study was to compare 2-hour postprandial glucose
      measurements with the standard 1-hour, 50 gm glucola screen as a predictor of
      gestational diabetes. STUDY DESIGN: In this prospective study, 448 patients were
      screened for gestational diabetes mellitus after 20 weeks' gestation. Each
      patient was instructed to ingest a meal containing at least 100 gm of
      carbohydrate, and 2 hours later a plasma glucose level was obtained. Shortly
      after, each patient was given 50 gm glucola followed by a 1-hour glucose
      measurement. If either screen showed a result of 140 mg/dl or more, a formal 3
      hour glucose tolerance test was done. Data were analyzed with use of the receiver
      operating characteristic curve. RESULTS: Of the 448 patients screened, 39 (8.7%)
      had a screening result of 140 mg/dl or greater and 16 (3.6%) of these had
      gestational diabetes mellitus. The receiver operating characteristic curve showed
      that the 1-hour glucose screen was more predictive of gestational diabetes than
      the postmeal assessment. The area under the receiver operating characteristic
      curve (plus or minus the SEM) for the 1-hour glucose test was 0.746 +/- 0.086 (p
      < 0.005) whereas the 2-hour postprandial test produced an area of 0.524 +/- 0.097
      (p = NS). The range of optimal 1-hour glucola discriminatory values was 182 to
      190 mg/dl. Thus the critical cutoff value of the 1-hour glucola test that
      minimizes false-positive results and maximizes true-positive screening for
      gestational diabetes is 182 mg/dl or greater. CONCLUSIONS: The 1-hour glucola
      test is a reliable screening test for gestational diabetes mellitus whereas the 2
      hour post-prandial test is not.

PMID- 9527947
TI  - Strategies women engage in when managing preterm labor at home.
AB  - Despite widespread efforts to prevent preterm birth in the United States, greater
      than 10% of the more than 4 million births that occur each year are preterm. Up
      to 75% of morbidity and mortality in infants is linked to preterm labor and
      birth. Bed rest, which may have adverse physical and psychologic effects, is
      commonly prescribed to manage preterm labor. This study describes the experience
      of women in programs of home management for preterm labor. Interview data from 25
      women treated at home for preterm labor were analyzed with the grounded theory
      method. Findings from this study indicate that the process of home management of
      preterm labor involves managing activity restriction. Women employed certain
      strategies when demands from relationships, households, and careers competed with
      the prescription of bed rest. These strategies included cheating, piggybacking,
      and testing the limits of their activity restriction. Implications for research
      and practice are suggested.

PMID- 9527948
TI  - Accuracy of different methods for heart rate determination during simulated
      neonatal resuscitations.
AB  - OBJECTIVE: We hypothesized that during a simulated neonatal resuscitation, heart
      rate determination with the Neonatal Resuscitation Program's (NRP) 6-second
      method is difficult and results in inaccuracies. We tried to determine whether a
      simple electronic timing device improves accuracy of heart rate determination.
      METHODS: One-hundred fourteen clinicians determined four heart rates under
      conditions simulating a resuscitation by three different methods: their own
      method, NRP's 6-second method, and an electronic timing device method. Responses
      were scored as correct if they would have resulted in the same intervention as
      called for by NRP criteria for each specific heart rate tested. RESULTS: Of 1368
      total responses, 267 (19.5%) were incorrect, which could have led to either an
      inappropriate intervention or lack of an appropriate intervention. The electronic
      timing device resulted in fewer errors (4%) compared with when clinicians used
      their own methods (32%) and the NRP's 6-second method (22%). CONCLUSION: The use
      of a simple electronic timing device improves accuracy of heart rate
      determination compared with the NRP's 6-second method or when clinicians use
      their own methods.

PMID- 9527949
TI  - Issues in determining and measuring adequacy of prenatal care.
AB  - Research has demonstrated that adequate prenatal care is an effective
      intervention that improves pregnancy outcomes, including reducing infant
      mortality rates. Currently, there are three methods to determine the adequacy of
      prenatal care, including American College of Obstetricians and Gynecologists
      Standards, Kessner Index, and Adequacy of Prenatal Care Utilization Index. All
      three methods have been used to measure prenatal care for women with low-risk
      pregnancies. Their use in women with a high-risk pregnancy is problematic. Use of
      a ratio index for women with a high-risk pregnancy is suggested. Following the
      criteria suggested by the Public Health Expert Panel on the Content of Prenatal
      Care to assess the effectiveness of prenatal care is recommended. Evaluating both
      quantity and content of prenatal care visits would more accurately reflect
      adequacy of prenatal care.

PMID- 9527950
TI  - Fetal compromise caused by maternal carbon monoxide poisoning.

PMID- 9527952
TI  - Fetal heart rate monitoring casebook. Fetal heart rate monitoring in fetuses with
      congenital anomalies.

PMID- 9527953
TI  - Special imaging casebook. Nager's syndrome.

PMID- 9527951
TI  - Mosaic trisomy 8: a cautionary note regarding missed antenatal diagnosis.
AB  - Chromosomal analysis of fetal cells is a commonly used, safe, and highly accurate
      procedure. The rate of false-negative results is unknown. Recent experience at
      four centers suggests that there may be a particular likelihood for mosaic
      trisomy 8 to be missed with routine antenatal diagnostic procedures. This report
      reviews these cases, the characteristic findings of mosaic trisomy 8, and the
      tissue-specific differential yield of chromosomal analysis that may contribute to
      the increased risk of missed antenatal diagnosis in patients with this disorder.

PMID- 9527954
TI  - Psychotherapy supervision in the 21st century. Some pressing needs and impressing
      possibilities.
AB  - As a professional and educational service, psychotherapy supervision looms large
      in importance. Yet if psychotherapy supervision is to most viably advance in the
      century ahead, a number of pressing measurement, research, and training/practice
      needs cry out to be better addressed. Ten such needs are identified by drawing on
      recent major research reviews and other substantive supervision publications. The
      author concludes that better addressing these needs would expand and fortify the
      empirical base of psychotherapy supervision and also enhance its training and
      practice base.

PMID- 9527957
TI  - Early identification of treatment failures in short-term psychotherapy. An
      assessment of therapeutic alliance and interpersonal behavior.
AB  - Early sessions of patients categorized as dropouts (n = 25), good outcome (n =
      28), and poor outcome (n = 20) completers of a 40-session protocol of short-term
      psychotherapy were compared to determine predictive validity of in-session
      measures of therapeutic alliance and interpersonal behavior (Working Alliance
      Inventory, Session Evaluation Questionnaire, and Interpersonal Adjective Scale).
      A number of significant differences were found among the three groups: both
      patients and therapists in the dropout group rated the relationship as more
      problematic than those in the good outcome group, and patients in the dropout
      group also rated the relationship as more problematic than those in the poor
      outcome group, while therapists' ratings did not distinguish dropouts from poor
      outcome. Differences between good and poor outcome groups were nonsignificant.
      These findings have clinical significance, particularly in early identification
      of patients at risk for treatment failure.

PMID- 9527955
TI  - Guided imagery treatment to promote self-soothing in bulimia nervosa. A
      theoretical rationale.
AB  - Bulimia nervosa (BN) has been described as involving impairment in affect
      regulation and in self-soothing. Such a conceptualization suggests the need to
      design treatments that specifically target these problems in order to assist
      individuals with BN in comforting themselves. A model of guided imagery therapy
      suggests that imagery therapy has multiple levels of action and can assist these
      individuals in the regulation of affect by providing an external source of
      soothing and also by enhancing self-soothing. The authors illustrate the model
      with a case example and report the results of a study in a clinical sample of BN.

PMID- 9527956
TI  - A match made in heaven? A pilot study of patient-therapist match.
AB  - The authors report on a study of patient-therapist match in 50 psychodynamic
      psychotherapy dyads. Sixty-six percent of patients and therapists agreed about
      the quality of the match, with 58% of patients and 56% of therapists reporting
      that the match was positive. Positive match correlated with positive patient and
      therapist assessments about the progress and process of therapy, but not with
      perceived similarity of personal characteristics. Patients' and therapists'
      perceptions about their similarities and differences from one another did not
      correlate. This study suggests it is both possible and important to gather data
      from both patient and therapist when studying match.

PMID- 9527958
TI  - What's in a case formulation? Development and use of a content coding manual.
AB  - A case formulation content coding method is described and applied to the
      formulation section of 56 intake evaluations randomly selected from an outpatient
      psychiatric clinic. The coding manual showed good reliability (mean kappa = 0.86)
      across content and quality categories. Although 95% of the formulations included
      descriptive information, only 37% addressed hypothesized predisposing life events
      accounting for the individual's presenting problems, and 16% included a
      precipitating stressor. Only 43% inferred a psychological mechanism, 2% inferred
      a biological mechanism, and 2% mentioned sociocultural factors. Formulations were
      more descriptive than inferential, more simple than complex, and moderately
      precise in use of language. In sum, clinicians used the formulation primarily to
      summarize descriptive information rather than to integrate it into a hypothesis
      about the causes, precipitants, and maintaining influences of an individual's
      problems.

PMID- 9527959
TI  - Shame-related states of mind in psychotherapy.
AB  - Current theory on self-conscious emotions emphasizes the importance of shame
      related phenomena in psychopathology and psychotherapy. An appreciation of
      manifestations of shame in psychotherapy greatly deepens our ability to connect
      with and understand our patients' experience. The relative salience of the shame
      prone patient's devalued-self or devaluing-other internalizations will have
      critical importance in the psychotherapy setting, guiding the types of
      interventions and stances that are most helpful. Knowledge of some predictable
      shame-related transactions involving envy, blaming, or overzealous probing can
      help the psychotherapist preempt mobilization of unnecessary levels of shame in
      treatment.

PMID- 9527960
TI  - A group cognitive-behavioral and process-oriented approach to treating the social
      impairment and negative symptoms associated with chronic mental illness.
AB  - Major changes in health insurance have brought challenges in managed mental
      health care services to the forefront. Given slim capitation margins, brief
      treatment with proven efficacy had become the standard. These developments have
      significant ramifications for the treatment of chronic mental illnesses, which
      often require lifelong treatment. Efficacious short-term group treatment may help
      fill the gap between quality of care and the ideal economic allocation of mental
      health care services for people with chronic mental illnesses. The present
      treatment outcome study was designed to determine the extent to which Interactive
      Behavioral Training (IBT)--a group psychotherapy model that actively combines
      cognitive-behavioral and group process techniques--can provide significant gains
      for people who suffer from chronic and debilitating social impairment and
      negative symptoms.

PMID- 9527961
TI  - Safe Practices for Parenteral Nutrition Formulations. National Advisory Group on
      Standards and Practice Guidelines for Parenteral Nutrition.

PMID- 9527962
TI  - Effect of parenteral medium- and long-chain triglycerides on lymphocytes
      subpopulations and functions in patients with acquired immunodeficiency syndrome:
      a prospective study.
AB  - BACKGROUND: Total parenteral nutrition (TPN) may offer significant clinical
      benefit in malnourished patients with acquired immunodeficiency syndrome (AIDS).
      However, the immunologic effect of parenteral lipids remains unknown in these
      severely immunodepressed patients. METHODS: We undertook a prospective randomized
      double-blind multicenter study comparing the effects of two i.v. lipid emulsions
      used during TPN: long-chain triglycerides (LCT) or balanced emulsion of long-and
      medium-chain triglycerides (LCT/MCT). Thirty-three AIDS patients requiring TPN
      for wasting and reduced oral intake were allocated randomly to receive a ternary
      TPN mixture consisting of 1.5 g/kg/d proteins, 18 kcal/kg/d lipids, and 12
      Kcal/kg/d carbohydrates for 6 days. The following tests were performed at days 0
      and 7: immunoglobulins, complement fractions, lymphocyte subpopulations count,
      and lymphocyte proliferation with mitogens. RESULTS: Patients were all severely
      malnourished (weight loss: -14.0 +/- 1.3 kg). No clinical or biological
      differences were observed between the groups at baseline. At day 7, both groups
      reported a significant increase in weight. Patients in the LCT group exhibited a
      significant decrease in phytohemagglutinin A response (p = .04) compared with
      baseline. Patients in the LCT/MCT group exhibited a lower level of IgM (p = .03)
      and significant increase in C3 fraction (p = .03) compared with baseline. They
      also showed a tendency to have a higher CD4/CD8 lymphocyte ratio (p = .07),
      whereas other immunological parameters remained unchanged CONCLUSIONS: Parenteral
      ternary mixture containing LCT or LCT/MCT are clinically well tolerated in AIDS
      patients over 6 days. With 2 g/kg/d of lipids, LCT seems to induce significant
      abnormalities in lymphocyte function. Such abnormalities are not observed with
      LCT/MCT.

PMID- 9527963
TI  - Early postoperative glucose control predicts nosocomial infection rate in
      diabetic patients.
AB  - OBJECTIVES: To determined the relationship between perioperative glucose control
      and postoperative nosocomial infection rate is 100 consecutive diabetic patients
      undergoing elective surgery. DESIGN AND PATIENTS: One hundred initially
      uninfected diabetic patients undergoing elective surgery were prospectively
      monitored for perioperative glucose control and postoperative nosocomial
      infection rate. Glucose control was determined by the attending surgeon or
      diabetologist. SETTING: A large tertiary care hospital that serves as the in
      patient facility for a local diabetes center. MAIN OUTCOME MEASURES: All patients
      were screened for infection preoperatively. Only initially uninfected patients
      were enrolled, and all patients received perioperative antibiotic coverage.
      Perioperative glucose control and postoperative nosocomial infection rate were
      monitored prospectively. APACHE II scores were determined on all patients.
      Patients were stratified into two groups: those with relatively "good"
      perioperative glucose control (all values < or = 220 mg/dL) and those with "poor"
      control (at least one value > 220 mg/dL). Contingency tables were generated,
      comparing nosocomial infection rates vs perioperative glucose control.
      Correlation coefficients between APACHE II score and maximum and mean glucose
      values were also determined. RESULTS: A serum glucose > 220 mg/dL on
      postoperative day one (POD 1) was a sensitive (87.5%) but relatively nonspecific
      (33.3%) predictor of the later development of postoperative nosocomial infection.
      In patients with hyperglycemia (> 220 mg/dL) on POD 1, the infection rate was 2.7
      times that observed (31.3% vs 11.5%) in diabetic patients with all serum glucose
      values < 220 mg/dL. When minor infection of the urinary tract was excluded, the
      relative risk for "serious" postoperative infection increased to 5.7 when any POD
      1 blood glucose level was > 220 mg/dL. On the basis of correlation coefficients
      between serum glucose values and APACHE II score, only 18% of the variance in the
      highest serum glucose could be explained by disease severity alone. CONCLUSIONS:
      We conclude that diabetic patients undergoing major cardiovascular or abdominal
      surgery have an increased risk of infection that is further exacerbated by early
      postoperative hyperglycemia. The high rate of nosocomial infection observed in
      diabetic patients with poor glucose control suggests that hyperglycemia itself
      may be an independent risk factor for the development of infection. Efforts to
      improve perioperative glucose homeostasis in diabetic patients may reduce the
      incidence of nosocomial infection and thereby improve outcome.

PMID- 9527964
TI  - Urinary 3-methylhistidine excretion: association with total body skeletal muscle
      mass by computerized axial tomography.
AB  - BACKGROUND: The urinary excretion of endogenous 3-methylhistidine (3-MH) has been
      proposed as a predictor of skeletal muscle mass (SM). In this study, we report
      the relationship between 24-hour urinary 3-MH excretion and SM. METHODS: Total
      body SM was measured by multiscan computerized axial tomography (CT) in a sample
      of 10 healthy adult men who followed a meat-free diet for 7 days. 3-MH was
      measured during the last 3 days of the meat-free diet protocol on consecutive 24
      hour urine collections. RESULTS: The 3-MH excretion was 216.3 +/- 44.7 mumol/d
      (mean +/- SD) and was found well associated with SM (in kilograms), SM = 0.0887 x
      3-MH + 11.8; r = .88, p < .001. Compared with CT, the previous 3-MH-SM prediction
      equation suggested by Lukaski et al underestimated SM by an average of 8.9 kg in
      the 10 healthy men. This difference was caused by the Burkinshaw-Cohn neutron
      activation model, which underestimated SM and was used as the reference in the
      Lukaski method. CONCLUSIONS: Twenty-four-hour urinary 3-MH excretion can be
      applied for estimating SM in healthy adult men on a meat-free diet.

PMID- 9527965
TI  - Is vitamin K1 supplementation necessary in long-term parenteral nutrition?
AB  - BACKGROUND: I.v. lipid emulsions contain vitamin K in substantial quantities and
      in 1989, we therfore stopped supplying vitamin K1 to patients receiving home
      parenteral nutrition (HPN). METHODS: Nine patients (group I) receiving HPN before
      1989 (10 mg i.v. vitamin K1 supplementation weekly until 1989, which was
      discontinued thereafter) and six patients with an initial low plasma vitamin K1
      concentration (related to their malabsorption) (group II) receiving HPN after
      1989 were studied. Prothrombin time (PT), plasma vitamin K1 concentration, and
      vitamin K1, content in lipid emulsions were measured throughout the period of
      HPN. RESULTS: All lipid emulsions, except for Eurolip 20% and Clinoleic 20%
      (Baxter SA, Maurepas, France) contained vitamin K1, with concentration ranges
      from 179 +/- 39 to 353 +/- 78 ng/L. Group I patients had an initial high plasma
      vitamin K1 concentration due to the vitamin K1 supplementation. After this
      supplementation was discontinued, plasma vitamin K1 decreased and remained in
      normal ranges with a normal PT. Throughout the HPN period after 1989, patients
      received 255 +/- 104 micrograms of vitamin K1 weekly through lipid emulsions. The
      PT and plasma vitamin K1 concentrations in group II patients were restored by
      lipid emulsions, which contained 418 +/- 143 micrograms/wk of vitamin K1.
      CONCLUSIONS: In patients receiving i.v. lipids (except for Eurolip and
      Clinoleic), a normal vitamin K1 status can be maintained during long-term HPN
      without vitamin K1 supplementation. However, vitamin K supplementation cannot be
      abandoned until the vitamin K content of emulsions is standardized by
      manufacturers. A weekly supply of 250 to 400 micrograms of vitamin K1 is enough
      to maintain and even restore a normal vitamin K1 status in HPN.

PMID- 9527966
TI  - Neither intact nor hydrolyzed soy proteins elicit intestinal inflammation in
      neonatal piglets.
AB  - BACKGROUND: Efficacy of feeding hydrolyzed soy proteins to infants intolerant to
      cow milk proteins has not been determined fully. This study compared growth and
      intestinal responses of neonatal piglets fed formulas with hydrolyzed soy protein
      to piglets fed formulas with intact soy or cow milk (casein-whey) proteins.
      METHODS: Piglets (n = 40, day 2 postpartum) were fed commercial milk replacer
      until day 7 postpartum (designated day 0) and then were assigned randomly to
      casein-whey (CW) or soy (intact, SI; hydrolyzed SH) formulas to evaluate
      intestinal responses on days 0, 2, 5, and 10. RESULTS: Average daily gain was
      higher for CW (121 g/d; p < .05) compared with SI piglets 85 g/d); SH pig weight
      gain was intermediate (109 g/d). Villus height-to-crypt depth ratio in proximal
      jejunum was lower (p < .05) on day 2 than day 0 in soy-fed pigs and lower (p <
      .05) on day 5 than day 0 in CW pigs. Mucosal mast cells were generally higher in
      CW pigs compared with soy-fed pigs. Villus goblet cell numbers in the midjejunum
      of SH-fed piglets were lower (p < .05) on day 5 compared with day 0. On day 5,
      crypt goblet cell numbers were higher (p < .05) in the midjejunum of CW-fed
      piglets compared with SH-fed piglets with numbers intermediate for SI-fed
      piglets. Intestinal differences were not detected among dietary treatments for
      major histocompatibility complex class I and II gene expression, tissue
      concentrations of prostaglandin E2, or CD8+ T-cell numbers. CONCLUSIONS:
      Hydrolyzed soy proteins do not elicit intestinal inflammatory responses in
      piglets and may be viable alternatives to milk and intact soy proteins for
      feeding infants.

PMID- 9527967
TI  - Parenteral feeding alters the fatty acid composition of serum phospholipids of
      rabbits.
AB  - BACKGROUND: Cholestatic liver disease develops in 30% to 70% of neonates
      receiving total parental nutrition (TPN). We analyzed the fatty acid composition
      of serum phospholipids from control and TPN-fed rabbits to determine if TPN
      altered the fatty acid profile. METHODS: Eleven male New Zealand White rabbits
      aged 9 to 11 weeks received TPN, whereas 11 other rabbits were offered standard
      laboratory rabbit chow ad libitum. After 14 days on the prescribed diet, serum
      samples were analyzed for their phospholipid fatty acid content by gas
      chromatography. RESULTS: The proportions of palmitolenic (16:2n7), alpha
      linolenic (18:3n3), arachidic (20:0), and eicosaenoic (20:1n9) acids were
      significantly lower in the serum phospholipids of the TPN-fed animals compared
      with the control group. The proportion of docosahexaenoic acid (22:6n3), a fatty
      acid that is critical to the development of the nervous system, was increased two
      to threefold. CONCLUSIONS: The differences in proportions of fatty acids
      observed between control and TPN-fed animals indicate that a fatty acid
      elongation and desaturation pathways are perturbed in rabbits on TPN.

PMID- 9527968
TI  - Electrolyte abnormalities in patients with chronic renal failure receiving
      parenteral nutrition.
AB  - BACKGROUND AND METHODS: Chronic renal failure frequently is complicated by
      elevations in serum potassium, phosphate, and magnesium. Consequently, parenteral
      nutrition (PN) solutions used to treat malnourished patients with chronic renal
      failure usually are prepared with little supplementation of these cations. Four
      malnourished patients with chronic renal failure and electrolyte abnormalities
      are reported. RESULTS: Four patients developed significant hypophosphatemia 3 to
      5 days after starting PN. Although carbohydrate infused via PN initially was not
      excessive (1.4 to 2.0 mg/kg/min), two patients received additional dextrose
      through continuous ambulatory peritoneal dialysis (CAPD). Two of the four
      patients received insulin during PN. Other electrolyte abnormalities included
      hypomagnesemia (1 patient) and hypokalemia (3 patients). CONCLUSIONS:
      Malnourished patients with chronic renal failure receiving PN are at risk of
      developing electrolyte abnormalities, particularly hypophosphatemia. The
      electrolytes of these patients should be monitored closely when nutrition support
      is begun, and supplementation should be started as levels begin to fall within a
      normal range.

PMID- 9527969
TI  - Glutamine and nucleotide metabolism within enterocytes.
AB  - Glutamine has an important role as a source of energy for enterocytes. However,
      it may also have a key role as a source of nitrogen for the synthesis of
      nucleotides. The relative contribution of de novo synthesis and salvage pathways
      seems to be affected by the position of enterocytes within the crypt-villus axis
      as well as the dietary intake of nucleic acids and glutamine. Nucleotides are
      especially important to enterocytes during intestinal development, maturation,
      and repair. Hence an understanding of nucleotide metabolism within enterocytes
      has important implications regarding both the composition and route of
      administration of nutrient solutions. Many important questions remain unanswered,
      in particular: Does glutamine stimulate intestinal de novo pyrimidine synthesis
      via the action of carbamoyl phosphate synthetase I? Can de novo purine synthesis
      maintain intestinal purine pools in the absence of dietary nucleic acids? And,
      what are the specific effects of parenterally administered nucleotides on the
      metabolism and well-being of enterocytes? A greater understanding of these issues
      will lead to a more rational approach toward the nutritional modulation of gut
      dysfunction.

PMID- 9527970
TI  - Subcutaneous jejunostomy.

PMID- 9527971
TI  - Branched-chain amino acids in critically ill septic patients.

PMID- 9527972
TI  - "The divine impatience": ritual, narrative, and symbolization in the practice of
      martyrdom in Palestine.
AB  - Violence is obscured by habits of thought, which predispose us to reject that
      which falls outside of our notion of "normal" human behavior. By dismissing as
      incomprehensible, or "pathologic," embodied practices that do not correspond to a
      "rationally ordered" everyday life, some anthropologists concerned with issues of
      violence forsake a fundamental responsibility to foster an understanding of
      phenomena that affronts, offends, or questions our own cultural norms and
      assumptions. Situations of violence, whether due to contextual or individual
      instability, by definition defy pregiven notions of "rationality" and "normal
      behavior." This article is about Palestinian martyrs, youths killed in
      confrontations with the Israeli military. It seeks to identify the cultural and
      psychological processes that make Palestinian martyrdom possible within the
      specific context of Israeli military occupation. It elaborates the ritual,
      narrative, and symbolic dimensions of a practice that exists within a Palestinian
      discourse of sacrifice and of national liberation.

PMID- 9527974
TI  - Suffering child: an embodiment of war and its aftermath in post-Sandinista
      Nicaragua.
AB  - This article considers how the ripple effects of war and its aftermath are
      embodied and lived even after being mediated by time, space, and social status.
      Through a case study of a Nicaraguan boy and his natal family, I argue that the
      legacy of war, structural violence, and endemic poverty are chronic and lingering
      and emerge from internationally and locally produced traumatogenic social
      relations. I use a phenomenological approach to distress to minimize the clinical
      tendency to pathologize individual sufferers, and to illuminate the destructive
      capacities of politically and historically produced conditions of social "normal
      abnormality." The continuum of lived experience of social suffering is poignantly
      articulated by a member of one of society's most vulnerable sectors, a ten-year
      old child.

PMID- 9527973
TI  - Embodiment of terror: gendered violence in peacetime and wartime in Croatia and
      Bosnia-Herzegovina.
AB  - Gendered violence is not a special type of torture used only in war. Its roots
      are well established in peacetime. This article discusses parallels between the
      patterns of everyday domination and aggression during times of peace and war.
      Further, it discusses how metaphors and acts of rape in peacetime are transformed
      into symbols and acts of rape for wartime purposes. During peacetime the
      individual body, especially its essence--sexuality and reproduction--becomes the
      symbol of everyday domination and aggression. Wartime transforms individual
      bodies into social bodies as seen, for example, in genocidal rapes or ethnic
      cleansing, which are thought to purify the bloodlines. Then, institutions--that
      is, medical, religious, and government establishments--further reinforce the
      wartime process by manipulating the individual/social body into the body politic
      by controlling and defining "human life" and using political rapes to entice
      military action by the West. The final transformation (at the war's conclusion)
      is the reformation of the social body back into the individual body, making the
      individual body once again the focus of dominance and aggression as the
      acceptable social "order."

PMID- 9527975
TI  - Suffering the winds of Lhasa: politicized bodies, human rights, cultural
      difference, and humanism in Tibet.
AB  - Tibetan refugees and Western activists note that if universal human rights
      standards were enforced in China, Tibetans would suffer less and come closer to
      political independence. This article explores potential problems of universalism
      and individualism in human rights discourse by examining understandings of the
      body and suffering among Lhasa Tibetan women. Data are taken from accounts of
      political prisoners and women patients at Lhasa's traditional Tibetan medical
      hospital. The data suggest a collective subjectivity, based on ideas about karma
      and congruences of body, mind, and society that contrast with those found in
      international human rights discourse. Tibetans are forced to adopt universalist
      and individualist positions to make their claims for human rights heard while
      ironically articulating ideas about suffering that would contest such
      universalist positions. The article proposes a need for alternative
      conceptualizations of human rights taken from Tibetan epistemologies of
      suffering, and illustrates the utility of medical anthropological inquiries about
      embodiment and subjectivity for addressing larger political debates about human
      rights.

PMID- 9527976
TI  - Terror warfare and the medicine of peace.
AB  - Terror warfare's goal is to defeat political opposition by controlling
      populations through the fear of brutality. Mozambique's 1976-92 war stands as a
      prime example of this military strategy: over one million people, the vast
      majority of whom were civilians, were killed. Half of these casualties were
      children. Fully one-half of the population was directly affected by the war, and
      one-quarter had to flee their homes. As devastating as terror warfare is, it is
      destined to fail. People ultimately resist, and they do so in complex and
      creative ways. Rebuilding war-destroyed worlds, healing the wounds of violence,
      and crafting concepts of self-identity based on resistance to aggression become
      powerful conflict-resolution strategies among the average citizenry. The creative
      resources that Mozambicans developed to survive and end a very brutal war are
      among the most sophisticated I have seen anywhere in the world. Their war was
      against violence itself.

PMID- 9527977
TI  - The medical anthropology of political violence: a cultural and feminist agenda.

PMID- 9527978
TI  - [new one-week triple therapies with metronidazole for the eradication of
      Helicobacter pylori: clarithromycin or amoxycillin as the second antibiotic].
AB  - BACKGROUND: To compare the efficacy of two "new" one-week triple therapies (with
      omeprazole, metronidazole and clarithromycin or amoxycillin) for the eradication
      of Helicobacter pylori and healing duodenal ulcer. METHODS: Randomised
      therapeutic trial. Eighty-eight consecutive duodenal ulcer patients with H.
      pylori infection were studied. At endoscopy, biopsies from both gastric antrum
      and body were obtained for histologic study (H&E). Two different therapies were
      administered for one week: omeprazole (O) (20 mg b.i.d.) and metronidazole (M)
      (500 mg b.i.d.) associated with clarithromycin (C) (500 mg b.i.d.) (group OMC, n
      = 44) or amoxycillin (A) (1 g b.i.d.) (group OMA, n = 44). Endoscopy with
      biopsies was repeated one month after completing therapy, and a 13C-urea breath
      test was also performed. Compliance was evaluated by tablet count. Analysis of
      data: multiple logistic regression, intention-to-treat. Eradication was defined
      as the absence of H. pylori by all diagnostic methods. RESULTS: Mean age
      (standard deviation) was 45(14) years, 75% males. Distribution of variables was
      similar in both therapeutic groups. Forty-two patients in each group completed
      the protocol. Eradication was achieved in 90.5% (95% CI = 78-96%) in group OMC
      and in 57% (42-71%) in group OMA (p < 0.001). In the multivariate analysis the
      type of therapy was the only variable which influenced on H. pylori eradication
      (OR = 7.1; CI = 2.2-24; p = 0.001). Ulcer healing was demonstrated in 88% (75
      95%) of patients in group OMC and in 71% (56-83%) in group OMA (p = 0.1). Ulcer
      healing was higher when eradication was achieved (90%; 80-95%) than in H. pylori
      positive patients (50%; 31-69%) (p < 0.001). Eradication of H. pylori was the
      only variable which influenced on ulcer healing (OR = 9.3; CI = 2.8-31; p <
      0.001). CONCLUSION: The "new" triple therapy with omeprazole, metronidazole and
      clarithromycin (administered in a twice-a-day basis and only for one week) had an
      excellent efficacy for the eradication of H. pylori, significantly higher than
      that obtained with amoxycillin instead of clarithromycin. Both therapies achieved
      a high ulcer healing rate when H. pylori was eradicated, even with omeprazole
      administered only for one week.

PMID- 9527979
TI  - [Prevalence of nephropathy in type I diabetes].
AB  - BACKGROUND: Diabetic nephropathy is a serious complication of diabetes, of which
      there are few epidemiological data in Spain. The aim of this study is to
      determine diabetic nephropathy prevalence in a group of patients with type I
      diabetes mellitus, representative of the population of Barcelona, Spain,
      evaluating several risk factors related with its development. PATIENTS AND
      METHODS: 639 patients (296 males and 343 women), from 6 hospitals, selected
      according with the diabetes duration (194 between 5 and 9 years [group I], 227
      between 10 and 19 years [group II] and 218 with 20 years or more [group III])
      were studied. In all patients urinary albumin excretion and plasma levels of
      creatinine, HbA1c, cholesterol and triglycerides were determined. The presence of
      retinopathy, neuropathy, vasculopathy and tobacco consumption were also
      evaluated. RESULTS: The prevalence of diabetic nephropathy increased with longer
      diabetes duration (8.1% [CI: 4.3-11.9] in group I, 24.7% [CI: 19.1-30.3] in group
      II and 44.7% [CI: 38.1-51.3] in group III), as well as that of hypertension,
      diabetes complications, cholesterol and triglycerides plasma levels. Related to
      people with normal renal function, after logistic regression, microalbuminuria
      was associated with hypertension and longer diabetes duration. Clinical
      nephropathy (macroalbuminuria + renal failure) to hypertension, longer duration,
      hypertriglyceridemia, male sex and tobacco consumption. CONCLUSIONS: The
      prevalence of diabetic nephropathy in Barcelona area is high and similar to that
      observed in other european regions. Its existence is associated with other
      diabetic complications. In addition to the classic risk factors, tobacco
      consumption must also be considered as a factor for diabetic nephropathy.

PMID- 9527980
TI  - [antineutrophil cytoplasmic autoantibodies in inflammatory bowel disease].
AB  - BACKGROUND: The aim of the present study was to determine the prevalence and
      diagnostic usefulness of antineutrophil cytoplasmic antibodies (ANCA) in a
      Spanish population of patients with inflammatory bowel disease from the province
      of Tarragona. PATIENTS AND METHODS: One hundred and fifty-six sera obtained from
      116 patients with inflammatory bowel disease (75 ulcerative colitis and 41
      Crohn's disease) and 40 healthy controls were tested using an indirect
      immunofluorescence assay. RESULTS: ANCA were detected in 65% of patients with
      ulcerative colitis but in only 12% of patients with Crohn's disease (p < 0.01),
      and 2.5% of control subjects (p < 0.01). The overall sensitivity of the test for
      the diagnosis of ulcerative colitis was 65% with a specificity of 88% and a
      positive predictive value of 91%. Among patients with ulcerative colitis there
      was no relationship between the presence or titre of ANCA and the duration, the
      clinical course, the extent, the disease activity or the need for medical
      treatment. CONCLUSIONS: In the population studied, ANCA occur more commonly in
      ulcerative colitis than in Crohn's disease, as reported in other populations.
      Their determination in patients with inflammatory bowel disease may be useful to
      differentiate ulcerative colitis from Crohn's disease.

PMID- 9527981
TI  - [Diabetic nephropathy].

PMID- 9527982
TI  - [Non insulin dependent diabetes mellitus, lipid metabolism and atherosclerosis].

PMID- 9527984
TI  - [The project of a national control program for tuberculosis in Spain].

PMID- 9527983
TI  - [Hiccup and dysfunction of the inferior olivary complex].
AB  - Two patients with chronic hiccup and MRI demonstrated lesions at the level of the
      inferior olivary complex are here reported. Whereas the neurological examination
      was normal in case 1, case 2 had the syndrome of palatal myoclonus and
      progressive ataxia. In the case 1, extensive electrophysiological studies were
      consistent with hiccup, in the absence of any other disorder (in particular,
      there was no evidence of palatal myoclonus). These findings suggest that the
      dysfunction of the inferior olivary complex could be implicated in the
      pathogenesis of hiccup.

PMID- 9527985
TI  - [Dietary fiber (and II). Metabolism and physiologic implications].

PMID- 9527986
TI  - [The role of Helicobacter pylori in the origin of gastric cancer, and eradication
      therapy in chronic gastritis].

PMID- 9527987
TI  - [Evaluation of presurgical anxiety].

PMID- 9527988
TI  - [Committees on ethics and clinical investigation of the community of Madrid,
      Spain].

PMID- 9527989
TI  - How will the Human Genome Project improve our quality of life?

PMID- 9527990
TI  - Genetically engineered organic food?

PMID- 9527991
TI  - Helicobacter pylori: a surprisingly conserved bacterium.

PMID- 9527992
TI  - Antitumor effects of hCG in KS.

PMID- 9527993
TI  - HIV trial abandoned.

PMID- 9527995
TI  - More ado about cloning.

PMID- 9527996
TI  - FDA seeks "comfort factors" before removing hold on porcine xenotransplantation
      trials.

PMID- 9527997
TI  - Turning the frog into a princely model.

PMID- 9527998
TI  - One small StEP in molecular evolution...

PMID- 9527999
TI  - Mimic 1 of MUC1.

PMID- 9528000
TI  - Immunological right of veto.

PMID- 9528001
TI  - Before anyone knew the future nature of biotechnology.

PMID- 9528002
TI  - Pharmacogenomics: will the regulators approve?

PMID- 9528003
TI  - Role of morphogenetic proteins in skeletal tissue engineering and regeneration.
AB  - Morphogenesis is the developmental cascade of pattern formation and body plan
      establishment, culminating in the adult form. It has formed the basis for the
      emerging discipline of tissue engineering, which uses principles of molecular
      developmental biology and morphogenesis gleaned through studies on inductive
      signals, responding stem cells, and the extracellular matrix to design and
      construct spare parts that restore function to the human body. Among the many
      organs in the body, bone has considerable powers for regeneration and is a
      prototype model for tissue engineering. Implantation of demineralized bone matrix
      into subcutaneous sites results in local bone induction. This model mimics
      sequential limb morphogenesis and has permitted the isolation of bone morphogens,
      such as bone morphogenetic proteins (BMPs), from demineralized adult bone matrix.
      BMPs initiate, promote, and maintain chondrogenesis and osteogenesis, but are
      also involved in the morphogenesis of organs other than bone. The symbiosis of
      the mechanisms underlying bone induction and differentiation is critical for
      tissue engineering and is governed by both biomechanics (physical forces) and
      context (microenvironment/extracellular matrix), which can be duplicated by
      biomimetic biomaterials such as collagens, hydroxyapatite, proteoglycans, and
      cell adhesion glycoproteins, including fibronectins and laminin. Rules of tissue
      architecture elucidated in bone morphogenesis may provide insights into tissue
      engineering and be universally applicable for all organs/tissues, including bones
      and joints.

PMID- 9528004
TI  - Viral sequences enable efficient and tissue-specific expression of transgenes in
      Xenopus.
AB  - Expression of transgenes within a single generation by direct DNA injection into
      vertebrate embryos has been plagued by inefficient and nonuniform gene
      expression. We report a novel strategy for efficient and stable expression of
      transgenes driven by both ubiquitous and tissue-specific promoters by direct DNA
      injection into developing Xenopus laevis embryos. This strategy involves flanking
      expression cassettes of interest with inverted terminal repeat sequences (ITRs)
      from adeno-associated virus. Our results suggest that the ITR strategy may be
      generally applicable to other systems, such as zebra fish and embryonic stem
      cells, and may enable tissue-specific expression of transgenes in problematic
      contexts.

PMID- 9528005
TI  - Molecular evolution by staggered extension process (StEP) in vitro recombination.
AB  - We have developed a simple and efficient method for in vitro mutagenesis and
      recombination of polynucleotide sequences. The staggered extension process (StEP)
      consists of priming the template sequence(s) followed by repeated cycles of
      denaturation and extremely abbreviated annealing/polymerase-catalyzed extension.
      In each cycle the growing fragments anneal to different templates based on
      sequence complementarity and extend further. This is repeated until full-length
      sequences form. Due to template switching, most of the polynucleotides contain
      sequence information from different parental sequences. The method is
      demonstrated by the recombination of two genes encoding thermostable subtilisins
      carrying two phenotypic markers separated by 113 base pairs and eight other point
      mutation markers. To demonstrate its utility for directed evolution, we have used
      StEP to recombine a set of five thermostabilized subtilisin E variants identified
      during a single round of error-prone PCR mutagenesis and screening. Screening the
      StEP-recombined library yielded an enzyme whose half-life at 65 degrees C is 50
      times that of wild-type subtilisin E.

PMID- 9528006
TI  - Metal mediated sterol receptor-DNA complex association and dissociation
      determined by electrospray ionization mass spectrometry.
AB  - The vitamin D receptor (VDR) binds to specific DNA sequences termed vitamin D
      response elements (VDREs) thereby enhancing or repressing transcription. We have
      used electrospray ionization mass spectrometry to examine the interaction between
      the DNA-binding domain of the vitamin D receptor (VDR DBD) with a double-stranded
      DNA (dsDNA) sequence containing the VDRE from the mouse osteopontin gene. The VDR
      DBD was shown to bind to the appropriate DNA sequence only when bound to 2 moles
      of zinc (Zn2+) or cadmium (Cd2+) per mole of protein. Additional binding of Zn2+
      or Cd2+ by the protein caused the protein to dissociate from the dsDNA. These
      results show that the VDR DBD/DNA metal-dependent association occurs when the
      receptor is occupied by 2 moles of Zn2+ per mole of protein and that further
      binding of Zn2+ to the protein causes dissociation of the complex.

PMID- 9528007
TI  - Peptide mimics of the CTLA4-binding domain stimulate T-cell proliferation.
AB  - Phage library clones selected by a conformational epitope-recognizing and
      inhibitory monoclonal antibody may display moieties that mimic a receptor/ligand
      like three-dimensional structure. This pseudoreceptor/ligand should be able to
      bind to natural ligand/receptor molecules. We tested this idea using anti-T cell
      costimulatory molecule antibodies and successfully isolated phage clones with
      costimulatory effects on T-cell proliferation. This strategy facilitates the
      designing of regulatory peptide molecules in the absence of precise information
      about the structure-function relationships in receptor/ligand interactions.

PMID- 9528009
TI  - Peptide mimics of a tumor antigen induce functional cytotoxic T cells.
AB  - The ability to mimic peptide/peptide and/or peptide/carbohydrate structures may
      be important in generating cross-reactive antibodies for autoimmune and other
      diseases. We show that the peptide sequence DAHWESWL can mimic the conformation
      of the unrelated MUC1 peptide SAPDTRPAP(G). Mice immunized with mannan-MUC1
      peptides make cytotoxic T lymphocytes (CTLs) and are protected from MUC1+ tumors.
      We show that the same specific anti-MUC1 responses can be produced by immunizing
      with the DAHWESWL peptide; furthermore, specific tumor protection is obtained in
      a manner similar to that with MUC1 immunization. The DAHWESWL peptide
      immunization leads to CTLs that recognize H2Dd and H2Ld but not H2b or human
      leukocyte antigens-group A (HLA-A) *0201 presented MUC1 peptides. However,
      mutation of the DAHWESWL peptide to a more HLA-A*0201-compatible structure with
      appropriate anchors (DLHWASWV), leads to the production of CTLs in HLA-A*0201
      mice.

PMID- 9528008
TI  - Specific inhibition of CD4+ T lymphocytes by a hybrid antibody.
AB  - T lymphocytes are crucial in the defense against foreign intruders and cancerous
      growths. Yet, in circumstances such as transplantation or autoimmunity, T-cell
      mediated responses can be detrimental. Inhibition of these deleterious responses
      is currently achieved by drugs that induce general immune suppression. These
      compounds also impair the patient's defenses against infections. Strategies are
      now being sought that induce selective rather than generalized immune
      unresponsiveness. One such strategy is the ability to inhibit the activation of
      CD8+ T lymphocytes. As CD4+ T lymphocytes similarly participate in graft
      rejection and in autoimmune diseases, we have now developed a reagent to delete
      their activity. It comprises CD4 and an anti-MHC class II antibody. By virtue of
      the antibody's specificity for MHC class II molecules, this hybrid antibody (Hab)
      binds to class II molecules, thereby bringing CD4 accessory molecules to the
      surface of class II-bearing stimulator cells where they occupy CD4 binding sites
      on class II molecules. As a consequence CD4+ T cells with specificity to Hab
      coated stimulator cells cannot engage their CD4 molecules and are no longer
      activated. This Hab technology provides a strategy to offer specific rather than
      generalized immune suppression.

PMID- 9528010
TI  - Biomagnetic isolation of antigen-specific CD8+ T cells usable in immunotherapy.
AB  - Isolating antigen-specific T lymphocytes is hampered by the low frequency of the
      cells and the low affinity between T-cell receptors (TCR) and antigen. We
      describe the isolation and purification of antigen-specific CD8+ T lymphocytes
      from mixed T-cell populations. Magnetic beads coated with major
      histocompatibility complex class I molecules loaded with specific peptide were
      used as a substrate for T-cell capture. Low-frequency T cells, as well as T cells
      with TCR of low affinity for the antigen were captured on the beads. Following
      isolation and expansion, recovered cells specifically killed target cells in
      vitro, and displayed antiviral effect in vivo.

PMID- 9528011
TI  - Selected peptides targeted to the NMDA receptor channel protect neurons from
      excitotoxic death.
AB  - Excitotoxic neuronal death, associated with neurodegeneration and stroke, is
      triggered primarily by massive Ca2+ influx arising from overactivation of
      glutamate receptor channels of the N-methyl-D-aspartate (NMDA) subtype. To search
      for channel blockers, synthetic combinatorial libraries were assayed for block of
      agonist-evoked currents by the human NR1-NR2A NMDA receptor subunits expressed in
      amphibian oocytes. A set of arginine-rich hexapeptides selectively blocked the
      NMDA receptor channel with IC50 approximately 100 nM, a potency similar to
      clinically tolerated blockers such as memantine, and only marginally blocked on
      non-NMDA glutamate receptors. These peptides prevent neuronal cell death elicited
      by an excitotoxic insult on hippocampal cultures.

PMID- 9528012
TI  - Efficacy of a food plant-based oral cholera toxin B subunit vaccine.
AB  - Transgenic potatoes were engineered to synthesize a cholera toxin B subunit (CTB)
      pentamer with affinity for GMI-ganglioside. Both serum and intestinal CTB
      specific antibodies were induced in orally immunized mice. Mucosal antibody
      titers declined gradually after the last immunization but were restored following
      an oral booster of transgenic potato. The cytopathic effect of cholera holotoxin
      (CT) on Vero cells was neutralized by serum from mice immunized with transgenic
      potato tissues. Following intraileal injection with CT, the plant-immunized mice
      showed up to a 60% reduction in diarrheal fluid accumulation in the small
      intestine. Protection against CT was based on inhibition of enterotoxin binding
      to the cell-surface receptor GMI-ganglioside. These results demonstrate the
      ability of transgenic food plants to generate protective immunity in mice against
      a bacterial enterotoxin.

PMID- 9528013
TI  - Patenting transgenics in the European Union.

PMID- 9528014
TI  - Toxicology resources on the Internet.

PMID- 9528015
TI  - Functional antigenics.

PMID- 9528016
TI  - [Estimate of the prevalence of Huntington disease in the Valencia region using
      the capture-recapture method].
AB  - INTRODUCTION AND OBJECTIVE: The objective of this study was to estimate the
      prevalence of Huntington's disease in order to devise a programme for diagnosis
      and prevention. Because of the characteristics of this disease, which is
      hereditary and of low incidence, few epidemiological studies have been carried
      out in Spain. Many studies (Medline 1990-1996) give cross-checking of registers
      as the key to determining the relative extent of the illness. The findings of
      this comparison of registers are not limited to the numerical quantification of a
      health problem, but are combined with active case search strategies, since there
      is now an approximation of probability to a previously unknown area of the
      disease. MATERIAL AND METHODS: Prevalence in the Valencia Region (Spain), which
      has a population census of 3,873,812 inhabitants, was estimated by means of the
      probability method known as capture-recapture. The estimated maximum probability
      and its confidence interval were calculated. The sources of information used were
      clinical histories from the regional hospitals and official figures of registered
      deaths during the period 1987-1992. RESULTS: It was found that there were 41
      cases seen in the regional hospitals and 17 deaths recorded in the official
      statistics, while 4 cases coincided in both sets of statistics. Recovery of 45
      cases histories enabled an analysis to be made of the relationship between the
      disease, sex, age of onset of symptoms, and family history. CONCLUSION: The
      estimated prevalence was 5.38 x 10(5). The most notable finding was that of a
      systematically earlier onset of symptoms in women, which was greater when the
      family history was on the paternal side.

PMID- 9528017
TI  - [Clinical characteristics of Cuban epidemic neuropathy].
AB  - INTRODUCTION: At the beginning of 1992 an epidemic neuropathy was seen in Cuba.
      MATERIAL AND METHODS: To determine the clinical characteristics we studied the
      clinical and neurological features, cerebrospinal fluid, and did
      neurophysiological investigations and sural nerve biopsies. RESULTS: Sixty
      patients were studied. Of these, 42 (70%) had polyneuropathy which was
      predominantly peripheral and 18 (30%) had combined forms. Most patients had
      asthenia and weight loss. The polyneuropathic effects were mainly in the legs. In
      33.3% of the patients there were distal autonomic effects and sphincter
      disorders. Only 7 patients had hypoacusia. However, subclinical neurosensorial
      hypoacusia was seen in 33.3%. Optic neuropathy affected central vision
      bilaterally and symmetrically with temporal pallor of the papilla in half the
      cases. In 3 patients there was loss of ganglionar nerve fibres of the papillo
      macula bundle. The contrast sensitivity visual test was abnormal in some patients
      with peripheral polyneuropathy, showing subclinical optic neuropathy in these
      cases. Sensory neuroconduction suggested axonal neuropathy in 30 patients,
      demyelinating neuropathy in 5 patients, while the remainder were normal. Motor
      neuroconduction was normal in most patients. Sural nerve biopsy of 27 patients
      showed axon damage in 96.2% of cases. CONCLUSIONS: The clinical picture is
      similar to that seen in nutritional deficiencies and toxic processes.

PMID- 9528018
TI  - [Clinical-epidemiological characteristics of late onset multiple sclerosis].
AB  - INTRODUCTION: Multiple sclerosis (MS) is the most frequent demyelinating disorder
      of the central nervous system. It mainly affects young adults and it has been
      calculated that between 20% and 30% are of late onset (after the age of 40),
      presenting clinical features, a clinical course and prognosis which are specific
      to this disorder. MATERIAL AND METHODS: Between 1985 and 1994 we studied 297
      cases of MS (diagnosed according to the criteria of Poser) and found that in
      20.5% the illness had started when the patients were over the age the 40. RESULTS
      AND CONCLUSIONS: Certain aspects of the clinical features and course of the
      disorder were compared, taking the group of late onset cases and a randomized
      sample of 100 cases of early onset, showing that the symptoms and pyramidal signs
      were more frequent in the late onset group, whilst sensory and visual signs were
      commoner in the early onset group. In both groups there were more females. MS was
      defined according to Poser's criteria in 78.7% and 77% respectively. Chronic,
      primary and secondary progressive forms predominated in tire late onset group,
      whilst in the group with onset before the age of 40 there was a predominance of
      the exacerbating-remitting form.

PMID- 9528019
TI  - [Quality and life style as risk factors in acute cerebrovascular disease].
AB  - INTRODUCTION: In some series of patients with acute cerebral vascular disease
      (CVD) it has been seen that, prior to the episode of CVD, the patients already
      had a poorer quality of life than other people of their age. The object of this
      study is to evaluate their previous life style and quality of life as risk
      factors (RF) in acute CVD. MATERIAL AND METHODS: A case-control study was done of
      a total of 151 patients admitted to two hospitals with acute CVD and 151 persons,
      who were not hospitalized and acted as the control group, paired (one to one) for
      age, sex and hospital. In both groups data were collected regarding basic general
      health, previous quality of life (Nottingham Health Profile-NHP-, life style and
      self-perception of social support. The relative risks were estimated by
      calculating the odds ratios and conditional logistic regression. RESULTS: Regular
      moderate physical exercise acts as a protective factor with an OR of 0.32 (IC
      95%: 0.14-0.76). Consumption of tobacco and alcohol increased the risk of CVD but
      did not reach statistical significance. No relationship was found between
      perceived social support and risk of CVD. Physical mobility, evaluated using the
      NHP showed a statistically significant negative association with acute CVD (OR:
      0.32; IC 95%: 0.14-0.71). CONCLUSIONS: Our results seem to suggest that the
      previous overall quality of life cannot be considered a RF in acute CVD, except
      for physical mobility as evaluated on the NHP. Reduction of this constitutes a RF
      and moderate physical exercise behaves as a protective factor.

PMID- 9528020
TI  - [Stressful life events as risk factors in acute cerebrovascular disease].
AB  - INTRODUCTION: The influence of psychosocial stress on the origin of acute
      cerebral vascular disease (CVD) has received very little attention. The objective
      of this paper is to evaluate the role of psychosocial stress due to events
      occurring in daily life as a risk factor (RF) in acute CVD. MATERIAL AND METHODS:
      A case-control study was done of a total of 151 patients who were admitted to two
      hospitals with acute CVD and 151 persons, who where not hospitalized and acted as
      the control group, paired (one to one) for age, sex and hospital. In both groups
      data were collected regarding basic general health, consumption of tobacco and
      alcohol and stressful incidents (SI) in their lives during the previous two
      years. The stress derived from SI was measured on the 'Inventory of SI and Recent
      Experiences' of Holmes and Rahe. The frequency of serious SI was also considered.
      The relative risks were estimated by the odds ratio calculations. RESULTS: A
      positive association was found for the RF defined in relation to acute CVD. We
      did not find any relationship between psychosocial stress derived from SI and
      risk of acute CVD (either when considering scores on the Holmes and Rahe
      Inventory or evaluation of serious SI). CONCLUSIONS: Psychosocial stress from SI
      does not seem to represent a RF in acute CVD.

PMID- 9528021
TI  - [Interferon-beta 1B in the treatment of remittent-recurrent multiple sclerosis.
      Clinical experience of the Valencia group. Multiple sclerosis study group of the
      city of Valencia].
AB  - INTRODUCTION: Recombinant beta-1B interferon has been used in our country since
      the end of 1995 for treatment of remittent-recurrent multiple sclerosis (RRME).
      At the present time there are still gaps in the effectiveness, side-effects and
      management of patients on this treatment. OBJECTIVE: To determine the evolution,
      side-effects and practical difficulties involved in the management of patients
      with RRME given interferon beta-1B and prospectively followed up one year after
      starting treatment. MATERIAL AND METHODS: This paper gives a prospective
      description of 41 treated patients with an average follow-up of 254 days.
      RESULTS: The patients tolerated and followed their treatment well. Treatment was
      only withdrawn in two cases. We observed a 40% reduction in the annual incidence
      of exacerbations (with respect to previous years) and there was improvement on
      the amplified dysfunction scale of Kurtzke in the patients whose exacerbations
      were treated with megadoses of steroids. The side-effects were those we expected,
      apart from an increase in thyroid complications and the appearance of a
      depressive syndrome. Treatment did not have to be changed because of the side
      effects. In two patients with serious side-effects (thyroiditis and a depressive
      syndrome) the symptoms disappeared when treatment was stopped. CONCLUSION: The
      results and side-effects were similar to those published. We had fewer patients
      who withdrew from the trial. There were no cases of patients not following the
      prescribed treatment.

PMID- 9528022
TI  - [Prevalence of migraine in a sample population of school children].
AB  - INTRODUCTION: The object of this study was to determine the prevalence of
      migraine in school children in our area, since few such studies have been done.
      MATERIAL AND METHODS: The study was carried out by means of a questionnaire given
      to school children aged between 6 and 14. We selected a representative sample of
      the population, the size of which was determined by accepting as a reference
      value the 4% mentioned by Bille. The questionnaire was drawn up after a search of
      the literature for similar questionnaires and a preliminary trial on children
      known to suffer from migraine (giving a specificity of 96.6% and a sensitivity of
      96.5%). RESULTS: Using the criteria of Vahlquist there was a prevailence of 7.0%
      and with IHS of 6.7%. There was a predominance (not significant) of females
      (54.4%). In 89.1% there was a positive family history (parents and/or siblings)
      of migraine.

PMID- 9528023
TI  - [Cortical variations of the dimension of correlation in children with attention
      deficit hyperactivity syndrome].
AB  - INTRODUCTION AND OBJECTIVE: The syndrome of deficient attention and hyperactivity
      affects approximately 5% of children of school age. Clinically it is
      characterized by deficient attention, impulsiveness and excessive motor activity.
      Developments in nonlinear dynamic theory have made it possible to think of
      modelling cerebral activity as a dynamic system of chaotic type. One the most
      widely standardized measurements is the dimension of correlation (D2). In this
      paper we study the electroencephalographic traces of a control group of 9 healthy
      children and another group of 19 children with the syndrome of deficient
      attention, at rest and whilst carrying out a visuomotor task (Test of perception
      of differences). MATERIAL AND METHODS: The dimension of correlation was estimated
      for both groups. Statistical comparison was made between the cortical
      distributions of the D2 between both types of recordings and between both groups.
      RESULTS: The children with lack of attention showed a larger number of activated
      cortical areas than those of the control group when carrying out the same task.
      However, during the resting state there were no differences in the D2 between the
      control children and the children with deficient attention. The indicates that
      both groups have the same basal level of activation. CONCLUSION: The dimension of
      correlation is a method which permits the demonstration of an increase in
      neuronal activity in the stimulated areas, in this case in the occipital region.

PMID- 9528024
TI  - [Subdural effusion in type B Haemophilus influenzae meningitis. A study of 38
      cases].
AB  - OBJECTIVE: Studying clinical, laboratory and radiologic findings, as well as
      outcome, observed in patients with meningitis caused by Hib, and its relationship
      with subdural effusion. MATERIAL AND METHODS: Retrospective study of 38
      meningitis caused by Hib. Patients were aged between 3 months and 5 years.
      Imaging was performed in 26 cases (68%): CT in 21 children (55%) and cranial
      sonography in 11 cases (29%). EEG was made in 29 patients (76%) and auditory
      evoked potentials in 13 (34%). The mean follow-up period after discharge was 24
      months. RESULTS: Sixty-six per cent were male and 34% female. Eight cases had
      subdural effusion. These patients showed higher white cell counts in blood and
      CSF, higher levels of proteins in CSF, and lower levels of glucose in the same
      medium. They also had seizures before or during hospitalization, with higher
      frequency than those without subdural effusion (50% vs 26%) as well as more
      prolonged fever (127 vs 73 hours). No specific treatment was required in any
      case. CONCLUSIONS: Subdural effusion is one of the most frequent complications
      observed in meningitis. Patients frequently present more important clinical and
      laboratory alterations. This finding is not related with neurologic sequelae and
      they resolve spontaneously with time.

PMID- 9528025
TI  - [Age as source of variation in various parameters of 'delta sleep'].
AB  - INTRODUCTION: The clinic usefulness of a diagnostic test is in relationship to
      the precision with which measures the studied phenomenon. The lack of precision
      involve the reliability upon causing confounded results of the normal and
      diseased populations. OBJECTIVE: Since the sleep varies in function of the age,
      to find sleep parameters that fit better to the changes that the aging produces
      in the sleep. MATERIAL AND METHODS: Spectral analysis through the Fast Fourier
      Transformation of the ambulatory EEG of 28 healthy subjects. RESULTS: Maximum
      value of power (maximum depth) in a frequency of ended in a point of the sleep
      goes losing in a way specifies and systematical with the age. CONCLUSIONS: The
      variance accounted by this parameter is of the 87%, what, being tried to a
      phenomenon so variable as the sleep, supposes a interesting starting point to be
      applied to some pathologies in those which is presumed that the slow sleep (to
      which is attributed a paper in the cerebral restoration) is decreased.

PMID- 9528026
TI  - [Predictive value of serum ferritin in the prognosis of acute cerebrovascular
      accident].
AB  - INTRODUCTION: Recent studies show that a raised level of serum ferritin indicates
      a poor prognosis in CVA patients, as do the well-known hyperglycemia, dyslipemia
      and arterial hypertension. The evolution and prognosis of acute cerebrovascular
      accidents are determined by a series of factors, some of which can be modified.
      This leads to a search for factors which can be modified and therefore influence
      the course of the illness. OBJECTIVE: To determine the ferritin levels and other
      parameters during the course of the illness of patients with serious cerebral
      vascular pathology and evaluate their effect on prognosis. MATERIAL AND METHODS:
      A prospective study was carried out on patients diagnosed as having CVA, admitted
      to the Neurology Department of the Miguel Servet Hospital (Zaragoza) during 1994,
      and who were in neurological coma (Glasgow scale less than 7) during the first 24
      hours, and unable to swallow. The levels of various plasma parameters were
      determined (glucose, cholesterol, ferritin, etc.) on admission and then every 10
      days. CONCLUSIONS: Plasma ferritin levels higher than those considered normal by
      the laboratory, in the first few hours after CVA, are an independent predictive
      factor suggesting unfavourable evolution of the vascular condition. Equally,
      raised ferritinemia in the first weeks after CVA indicates a worse prognosis.
      This laboratory test may be carried out on patients with acute CVA to obtain more
      information on which to base the prognosis.

PMID- 9528027
TI  - [Medical editors' trial amnesty].

PMID- 9528028
TI  - [Neuroradiology: past and present].

PMID- 9528029
TI  - [Delayed diagnosis of phenylketonuria as the cause of mental retardation in an
      adolescent].
AB  - INTRODUCTION: The hyperphenylalaninemias (HFA) form a diverse group of recessive
      autosomic disorders. They are caused by defects in the hepatic system for
      hydroxylation of the amino acid phenylalamine to tyrosine. The estimated
      incidence is approximately 10 cases per 100,000 live births. Children with this
      metabolic disorder may present with varied neurological symptoms. Control of
      plasma levels, so that they are more normal as soon as possible after birth,
      significantly prevents mental retardation and other neuropsychological
      dysfunction. For this reason HFA has been included in neonatal screening.
      However, some patients are not detected on screening. When they are adults, these
      patients pose problems of diagnosis for neurologists who attend adults. CLINICAL
      CASE: We describe an adolescent with mental and linguistic retardation, in whom
      neonatal screening to rule out metabolic defects was normal. At the age of 15,
      the phenylalanine in blood and urine were found to be raised. On cerebral
      magnetic resonance changes typical of pheynylketonuria (PKU) were seen.
      CONCLUSIONS: The HFA should be considered as causes of cerebral dysfunction in
      adults, since in spite of neonatal screening, false negatives may occur. We
      describe a clinical case and consider different forms of hyperphenylaleninemias.
      Their diagnosis and treatment.

PMID- 9528030
TI  - [Early infantile epileptic encephalopathy and glycine encephalopathy].
AB  - INTRODUCTION: Early infantile epileptic encephalopathy (EIEE) with suppression
      burst activity in EEG (Ohtahara syndrome) is a rare type of epileptic
      encephalopathy in infancy and represents the earliest type of age-related
      symptomatic generalized epilepsy. The main etiologic factors associated to EIEE
      are cerebral dysgenesia and metabolopathies, principally nonketotic
      hyperglycinemia. CLINICAL CASE: We report a neonate with EIEE secondary to
      glycine encephalopathy, diagnosed by increased of LCR/plasma glycine index.

PMID- 9528031
TI  - [Neuroborreliosis in a patient with progressive supranuclear paralysis. An
      association or the cause?].
AB  - INTRODUCTION: Many different neurological conditions may be seen in the later
      stages of Lyme's Disease, such as blindness, epileptic crises, CVA,
      extrapyramidal disorders, amyotrophic lateral sclerosis, and dementia may be yet
      another form of presentation of chronic infection due to Borrelia burgdorferi
      (Bb). Progressive Supranuclear Paralysis (PSP), a disorder of unknown aetiology,
      considered to be the commonest cause of Parkinsonism-plus, one of the symptoms of
      which is dementia, has never been mentioned in this type of differential
      diagnosis. CLINICAL CASE: We present the case of a 78 year old man with sub-acute
      mental deterioration, Bb positive serology in both plasma and CSF, and with
      clinical and epidemiological features compatible with Lyme's Disease.
      Complementary tests were negative. The syndrome corresponded to Lyme's Disease
      and improved after treatment with ceftriaxona. CONCLUSIONS: We consider aspects
      of the aetiology of PSP which are still not clear. In our patient, the aetiology
      seemed to be Bb infection, according to the criteria of the original description
      of the disease and in view of the neuropathological findings which have shown Bb
      in the substancia nigra of the mid-brain and the existence of an animal model in
      which Bb shows a particular tendency to colonize infratentorial structures.

PMID- 9528032
TI  - [Horner's syndrome secondary to ophthalmic herpes zoster].
AB  - INTRODUCTION: Ophthalmoparesias is a frequent complication of ophthalmic herpes
      zoster. It occurs in 31% of all cases. However, the presence of Horner's syndrome
      during viral reactivation is a rarity which has only been previously described on
      two occasions, and never associated with cranial nerve involvement. CLINICAL
      CASE: We describe a patient with the first case of Horner's syndrome secondary to
      ophthalmic herpes zoster, with simultaneous, homolateral lesions of the third and
      sixth cranial nerves. Clinical evaluation, the course of the disorder, negative
      magnetic resonance studies and tests with cocaine and foledrin eye drops
      confirmed the presence of a post-ganglionar sympathetic lesion, probably situated
      in the ipsilateral cavernous sinus. CONCLUSIONS: Ophthalmoparesias as a
      complication of ophthalmic herpes zoster may have various origins. Diffusion of
      viral particles from the Gasserian ganglion and branches of the trigeminal nerve
      to adjacent structures, muscles, nerves and vessels, is the mechanism often
      mentioned. Presence of a simultaneous sympathetic lesion is very rare and of
      unknown pathology. However, it is probable that the origin of the lesion of the
      vegetative fibres is the same as that of the sensory or motor fibres, and
      adjacent inflammatory process caused by the virus extending. We analyze the
      factors involved in the low incidence of this association.

PMID- 9528033
TI  - [Familial periodic ataxia with myokymia sensitive to acetazolamide: a family
      case].
AB  - INTRODUCTION: Acetazolamide responsive hereditary paroxysmal cerebellar ataxia
      with myokymia is a type of autosomal dominant cerebellar ataxia which locus was
      found to be linked to the short arm of chromosome 12 and the etiology is unknown.
      CLINICAL CASE: A 12 years-old man who suffered from childhood daily episodes of
      sudden attacks sport induced with giddiness, ataxia and dysarthria for minutes.
      The familial history shows the same clinical findings in three generations.
      Intercritical general neurologic evaluation is otherwise normal. The following
      tests were performed with normal results: Biochemistry, electroencephalogram,
      cerebral magnetic resonance imaging. The electromyography showed myokymic
      discharges. The patient's symptoms improve on treatment with acetazolamide
      immediately. CONCLUSIONS: Acetazolamide responsive hereditary paroxysmal
      cerebellar ataxia with myokymia needs to think on it to be diagnosed. No typical
      complementary test (electromyography exception) induces to base diagnosis in the
      clinical findings, the familial history and the fast clinical improvement after
      starting treatment with acetazolamide.

PMID- 9528034
TI  - [Partial simple vegetative crisis: importance of electroencephalographic
      findings].
AB  - INTRODUCTION: 50% of the patients with cerebral tumours present with epileptic
      crises, which may be partial or generalized. The commonest partial crises have
      motor symptoms. These make up 30% of the simple partial crises. Partial simple
      crises with purely vegetative-type symptoms are very uncommon (less than 5%).
      They are considered to be caused by discharges in the internal regions of the
      temporal lobes, mainly in the limbic system. This means that it is very difficult
      to identify them using techniques of surface EEG. CLINICAL CASE: We describe the
      case of a patient with a cerebral tumour. The initial clinical features were
      short episodes of generalized coldness and sweating which had been present for
      the previous two weeks, without any other symptoms. During a routine EEG, focal
      critical paroxystic activity was recorded in the right temporal region. This
      coincided with a clinical episode similar to those described. CONCLUSIONS: The
      episodes were labelled partial simple vegetative crises. In this case the EEG was
      crucial for diagnosis and subsequently to recommend suitable treatment. However,
      difficulty in recording this type of crisis with a surface EEG makes correct
      diagnosis of these patients very difficult, since the epileptogenic focus is
      deeply situated.

PMID- 9528035
TI  - [State of bilateral opercular disorder and pseudobulbar paralysis of late onset
      in unilateral perisylvian dysplasia].
AB  - INTRODUCTION AND CLINICAL CASE: We come up the case of a six and a half year old
      girl suffering from right unilateral perisylvian cortical dysplasia who present
      left spastic hemiparesia, mirror movements and language disorder. She made her
      epileptic debut at the age of four and a half with myoclonic absences which
      responded to valproate treatment. At the age of five she began with biopercular
      status epilepticus shown as pseudobulbar palsy as diffusion of discharges from
      the dysplasia localization to the contralateral one. These episodes look places
      with variable duration from one hour to one month and finished after medical
      treatment or spontaneously. At the present a pseudobulbar palsy persistence and a
      bilateralization in the symptoms is observed.

PMID- 9528036
TI  - [Spontaneous spinal extradural hematomas: report of two cases].
AB  - INTRODUCTION AND CLINICAL CASES: We present two cases of spontaneous spinal
      extradural hematoma, which occurred in 1996 and were admitted to and operated on
      by our Department. Both patients were women. No cause for the bleeding was found
      in either case. Both presented with the site of the lesion in the thoracic spine,
      although at different levels. There was acute onset of the clinical condition.
      The best diagnostic procedure was MR. The treatment of choice was surgical and
      the results related to the rate of onset of the clinical picture and the time
      elapsed before operation. CONCLUSION: The form of presentation is discussed,
      together with the importance of early diagnosis and the relation to emergency
      surgical treatment.

PMID- 9528037
TI  - [Transdural anastomosis in a juvenile form of moyamoya disease].
AB  - INTRODUCTION: Moya-Moya disease has a low prevalence and world-wide distribution,
      with greater incidence in the first 5 years of life (juvenile form) or in the
      third decade (adult form). Stenosis of the intracranial portion of the internal
      carotid artery leads to secondary establishment of intracranial compensating
      anastamoses at different levels (leptomeninges, basal ganglia and transdural). We
      present the case of a 7 year old boy who presented clinically with choreiform
      movements and later had a cerebral infarct. On angio-MR and MR studies we
      observed the typical smoky image together with development of additional
      compensatory transdural anastomoses from the superficial temporal and ophthalmic
      arteries to the anterior and middle cerebral arteries.

PMID- 9528038
TI  - [Incidence of the standardization of scientific journals in the transfer and
      evaluation of scientific information].
AB  - INTRODUCTION AND OBJECTIVE: I analyze the repercussions of standardization of
      scientific publications in general, and of journals in particular, on the
      processes of scientific information transfer, diffusion and evaluation.
      DEVELOPMENT: Standardization facilitates the work of all agents in the primary
      (authors, publishers and readers) and secondary communication systems
      (librarians, information scientifics). Compliance with standards influences the
      presence of journal in bibliographic databases and de quality of bibliometric
      studies. Standardization thus has repercussions in the evaluation of science.

PMID- 9528039
TI  - [Shared responsibility in expert review of original articles].
AB  - OBJECTIVE: To point out some defects in the process of selection of manuscripts
      for publication in the primary biomedical literature, and offer some
      recommendations for reviewers, editors and authors that can enhance the
      accountability and effectiveness of peer review. DEVELOPMENT: Although peer
      review is said to guarantee the quality of scientific journals, there are no
      experimental data to prove this statement, and research is urgently needed to
      clarify the advantages and disadvantages of the system. The term 'peer review' is
      used for very different processes, and there is no commonly accepted definition.
      To ensure professionalism and accountability, all steps of the peer review
      process need to be well thought out and documented, and the responsibilities of
      all persons involved need to be clearly defined. CONCLUSIONS: To ensure
      accountability in the peer review system and reduce the probability of errors and
      abuse, every journal should have in place a set of internal guidelines of good
      practice for editorial staff, reviewers and authors, and this information should
      be made widely available.

PMID- 9528040
TI  - [Epidemic neuropathy: proposal and arguments to rename Strachan disease as
      Strachan and Madan disease].
AB  - INTRODUCTION: Strachan's disease is a condition which mainly affects the nervous
      system. It is characterized by optic, auditory and peripheral neuropathies and
      lesions of the skin and mucous membranes. In 1955 Miller Fisher gave it this
      name, since the clinical condition described by Henry Strachan in Jamaica during
      the nineteenth century was similar to that seen in Canadian prisoners-of-war in
      Japanese concentration camps during the Second World War. DEVELOPMENT: Since
      there are similarities between these clinical disorders and the major neuropathic
      epidemic seen recently in Cuba, we have reviewed and compared the endemic and
      epidemic conditions of similar characteristics seen in Cuba during the nineteenth
      and twentieth centuries. We also make a detailed review of a similar condition
      described in 1898-1900 by Doctors Madan, Lopez and Santos Fernandez, during the
      last Cuban War of Independence. This seems to be one of the earliest descriptions
      of the disorder. We also consider the so-called Strachan's syndrome or disease,
      and descriptions from the same period of tobacco-alcohol amblyopia and beriberi.
      These conditions seem to have been very similar to the so-called optical and
      peripheral forms of the current Cuban epidemic. It is concluded that the clinical
      characteristics of the recent Cuban neuropathic epidemic, at least in the optical
      form, were seen to be endemic during the nineteenth century. In many cases this
      was considered to be alcoholic amblyopia or some other obscure neuropathy which
      became epidemic during periods of severe economic depression. CONCLUSION: Madan
      gave a full description of the disorder at the same time as Strachan did. In 1898
      he also suggested its true cause and died trying to relieve it. We therefore
      consider that Strachan's syndrome should be renamed the Strachan-Madan syndrome.

PMID- 9528041
TI  - [Madopar: more than 20 years].
AB  - OBJECTIVE: To review the main landmarks which led to the introduction of levadopa
      in the the treatment of Parkinson's disease and the impact of levadopatherapy.
      DEVELOPMENT: The introduction of levadopa was based on the results of basic
      scientific investigations in neurochemistry and neuropharmacology. In 1959 the
      possibility of dopamine being a neurotransmissor, and the role it plays in motor
      control, had been discovered. In 1960, Hornykiewiez and Ehringer published a
      paper on the existence of a marked deficit of dopamine in the caudate nucleus and
      putamen of patients with Parkinson's disease. Almost simultaneously, Birkmayer
      and Barbeau treated their patients with levadopa for the first time. However,
      levadopa was not introduced into clinical practice until 1967 and 1969 when
      Cotzias published papers establishing the principles of levadopatherapy as we now
      know it. Introduction of levadopa produced a markedly beneficial effect on the
      course and mortality of Parkinson's disease. However, it was soon seen that
      progression of the disease was not halted and that undesirable side effects
      appeared in patients on long-term treatment. This has led to the development of
      strategies to prolong the beneficial effects of levadopa and minimize its side
      effects. CONCLUSION: More than 25 years after the introduction of
      levadopatherapy, it is still the mainstay of the treatment of Parkinson's
      disease, in combination with other medical and surgical treatment. Definitive
      treatment, however, will have to wait until the cause of this illness is fully
      understood.

PMID- 9528042
TI  - [Treatment of carotid cavernous fistulas].
AB  - INTRODUCTION: Carotid-cavernous fistulas (CCF) are anomalous communications
      between the carotid arterial and carotid venous circulation of the cavernous
      sinus. The arterio-venous shunt leads to increased congestion of the orbit and
      causes the characteristic clinical picture typical of this condition; medusa's
      head, proptosis, raised intra-ocular pressure and tinnitus. DEVELOPMENT:
      Classically, acute onset of these signs after trauma has been considered to be
      due to CCF. However, 25% of CCF are low flow and have an insidious clinical
      course which is concealed and difficult to diagnose. Primary search depends
      initially on the use of ultra-sound (Eco-B and Eco-Doppler). In doubtful cases
      vascular study is done using non-invasive methods such as angio-CT, angio-MR and
      Divas. Intra-arterial angiography is left until the preoperative study is done.
      CONCLUSIONS: Whilst 90% of medium and high flow FCC require neurosurgical
      treatment for the gravity of the symptoms, only 25% of the low flow FCC require
      it. The latter are initially treated conservatively.

PMID- 9528043
TI  - [Neuro-ultrasonographic evaluation of ischemic stroke].
AB  - INTRODUCTION AND DEVELOPMENT: The development of new management strategies for
      acute stroke demands better understanding of the ischemic mechanism,
      cerebrovascular anatomy, and cerebral hemodynamics for individual patients. The
      use of carotid duplex sonography, transcranial Doppler sonography, and
      echocardiography allows evaluation of the key areas of interest in a prompt,
      safe, accurate, and cost effective manner. CONCLUSIONS: Knowledge of these
      methods is essential for neurologist caring for patients with stroke.

PMID- 9528044
TI  - [Memory and learning: 'experience' and 'skill' of the brain].
AB  - OBJECTIVE: To describe the current typology and different processes involved in
      memory and learning, as well as adequate tests in the diagnosis of the mnesic
      disorders. DEVELOPMENT: We reviewed the most recent studies about functional and
      lesional neuroanatomy of memory and learning and their neurophysiological bases
      (cellular and biochemical), with special emphasis in studies published in the
      three last years. We structured a typological classification, we expose the
      processes involved in short-term and long-term memory, we detailed the mnesic
      processes of declarative and implicit type, and we expose profiles of amnesias
      frequent in the clinical neurology and neuropsychology. CONCLUSIONS: Memory is
      not a diffuse and unitary process in our brain, neither amnesia is an absolute
      loss of memory. The multidimensional combination of two temporary memories (short
      and long-term) and three mnesic processes ('working memory', explicit and
      implicit memory-learning) increases our capacity to memorize and learn, and it
      allows us to store the information in distinctive periods, with different
      mechanisms and covering different necessities. Patients with amnesia exhibit
      distinctive profiles of mnesic processes affected.

PMID- 9528045
TI  - [Attention: a complex cerebral function].
AB  - INTRODUCTION: Attention is a brain neurocognitive state of preparing what
      precedes perception and action, and is a result of cortical and subcortical
      networks. Attention selectively focuses our consciousness while filtering the
      constant flow of sensory information, selects competent parallel processing among
      stimuli and activates brain zones for ordering appropriate responses.
      DEVELOPMENT: From a neurofunctional point of view this paper reviews and
      describes attention as a brain function regulated by three interrelated systems:
      Alertness or arousal providing tonic attention, dependent on the mesencephalic
      reticular activating system and its connections: posterior attention or attention
      of perceptive selectivity that depends on zones of the right posterior parietal
      cortex and its connections; and, anterior attention or supervisory attention that
      regulates deliberate attention, and supported by zones of the anterior cingulate
      and lateral prefrontal cortex and the connections of the zones.

PMID- 9528046
TI  - [Spontaneous intracranial hematomas. A surgical solution?].
AB  - INTRODUCTION: Spontaneous intracranial haematomas pose a fundamental question for
      the neurosurgeon: Should he operate or not? The main objective of this paper is
      to consider recent ideas on this subject. A detailed review of the literature was
      carried out and then discussed. DEVELOPMENT: This study has been structured as
      supratentorial haematomas, infratentorial haematomas (cerebellum and brainstem)
      and multiple cerebral haematomas. We emphasize the importance of CT scanning to
      surgical decision-making. In supratentorial haematomas, surgery is considered to
      be indicated in patients with blood clots of between 2 and 3 cm in diameter, and
      whose neurological state is starting to deteriorate. Patients with cerebellar
      haematomas are classified into four groups, depending on the level of
      consciousness and the diameter of the clot. In these patients surgery is
      indicated basically in patients, both alert and somnolent, with haematomas
      greater than 3 cm. Medical treatment is recommended in patients with multiple
      haematomas and haematomas localized to the brain-stem. It is suggested that the
      best time to evacuate the haematoma is between 2 and 6 hours after onset.
      CONCLUSIONS: We consider that with the development of modern neuro-imaging
      techniques, intensive care units, neurological monitorization, developments in
      neurosurgical techniques with the use of magnification, the ultrasonic aspirator
      and stereotactic techniques, there will be more and more patients with
      spontaneous intracranial haematomas who can be successfully treated surgically in
      the next few years.

PMID- 9528047
TI  - [Somatostatin receptors in meningioma: diagnostic and therapeutic value].
AB  - OBJECTIVE: We discuss the diagnostic and therapeutic usefulness of the presence
      of somatostatin receptors (SR) in meningiomas. DEVELOPMENT: The SR are membrane
      receptors, may be saturated, have great affinity and pharmacological specificity
      for somatostatin (SS) and its analogues. SR have been found in 100% of the
      meningiomas studied. The presence of a large number of SR in different tumours
      permits gammagraphic detection in vivo by marking SS analogues with 1-231-DTPA
      and subsequent visualization using a gamma camera. This study may help to
      differentiate between meningiomias and other tumour lines. Experiments using
      different SS analogues have shown different degrees of affinity of these SS
      analogues for the different receptors. In various animal models a potent
      inhibitor effect on tumour growth has been seen following SS and its analogues.
      Unlike in hypophyseal adenomas and endocrine gastro-entero-pancreatic tumours,
      neither SS nor its analogues have shown any direct inhibitory action on the
      growth of meningioma cell cultures. Quite the opposite occurs. A small but
      significant stimulation of growth was seen in the presence of SS. CONCLUSIONS: We
      consider the detection of SR by isotopic marking of SS analogues is useful in the
      differential diagnosis of meningiomas. The therapeutic usefulness of the
      analogues of SS for treatment of meningiomas remains controversial. Further study
      of the different types of receptors and analogues is necessary.

PMID- 9528049
TI  - [In vitro models for the study of nerve lesions and potential neuroprotective
      drugs].
AB  - INTRODUCTION AND DEVELOPMENT: In order to study the neurotoxic effects of drugs
      and to search for neuroprotective agents, we need simple models that permit a
      quick screening of thousands of compounds. In vitro models with cellular cultures
      fulfill all this criteria and they are very appropriate to study the mechanism of
      action of drugs. As adult neurons are very difficult to maintain in culture, this
      kind of studies are carried out with fetal neurons, tumoral cells or chromaffin
      cells. CONCLUSIONS: This in vitro models have shown the neuroprotective effect of
      glutamate antagonists, calcium-channel blockers, free radical scavengers and
      other agents as CDP-choline, that promotes cellular membranes restoration.

PMID- 9528048
TI  - [The spectrum of prion pathology broadens: fatal familial insomnia].
AB  - INTRODUCTION: The small group of prion diseases, caused by accumulation in the
      brain of an abnormal protein characterized by its aggregation and relative
      resistance to proteases (the PrPSc) in man is comprised of Creutzfeldt-Jacob
      disease (CJE), the Gerstmann-Straussler-Scheinker syndrome, kuru and the newest
      addition which is fatal familial insomnia (FFI). DEVELOPMENT: FFI is a hereditary
      condition with dominant autosomal transmission, characterized clinically by
      progressive insomnia, dysautonomy, changes in the circadian rhythm of hormone
      secretion, motor signs and slight to moderate deterioration of cognition. The
      usual age of onset is between 40 and 60 years, and the course of the illness
      lasts between 7 and 18 months. The histopathological changes, involving neurone
      loss and reactive gliosis, particularly affect the anteroventral and dorsomedial
      thalamic nuclei. These lesions lead to insomnia and to autonomic and endocrine
      disorders. To a lesser extent and degree, lesions are seen in other thalamic
      nuclei, the cerebral cortex, inferior olives and the cerebellum. FFI and some
      families with CJE have the same mutation of the codon 178 of the protein prion
      gene (gene PRNP) with substitution of aspartic acid by asparagine. Polymorphism
      of codon 129, which codifies methionine or valine determines the development of
      the clinical and neuropathological phenotype of FFI or CJE respectively.
      CONCLUSIONS: The description of FFI and the detection of PrPSe in familial cases
      of diffuse subcortical gliosis has indicated the possibility that there may be
      other familial or non-familial neurodegenerative diseases caused by prions.

PMID- 9528050
TI  - [Kinematic deterministic chaos of fluids and fractal geometry in the carotid
      system].
AB  - INTRODUCTION: Atherosclerosis is a generalized vascular disorder which tends to
      be localized to specific arterial territories. At the bifurcation of the carotid
      artery there is a marked predisposition to form plaques of atheroma on the
      postero-external wall. This tendency is due to the kinematics of fluids and their
      particular morphological characteristics which are unique in the vascular system.
      The carotid tree is a physical, non-lineal or in 'non-equilibrium', dynamic
      system which depends on the fluctuating contribution of energy from the cardiac
      cycle. It has fractal geometry which follows the Law of Biology of maximum
      efficiency with a minimum of effort. DEVELOPMENT: The complexity of the
      relationship between the haemo-rheological and anatomical factors, and the
      periodic oscillation of flow does not permit use of simple models and classical
      determinist equations to describe idealized systems of continuous movement and
      Newtonian fluids. On the contrary, since we are considering a complex dissipative
      dynamic system. It has marked intrinsic operational freedom adapting its
      responses to external disturbances well, thus determining vasculo-cerebral
      autoregulation. The theories of Determinist Chaos and of the Science of
      Complexity imply the existence of emerging properties which exceed those of the
      individual elements in the dynamic systems in non-equilibrium, which tend to
      function in the 'frontier of chaos' at the critical points of phase transition.
      The carotid tree has non-linear properties, appearance of order and fractal
      'sibisemejanza'. Pseudo-chaotic vortices appear--in regions of phase transition
      between laminar flow and turbulence--with the emergence of a 'strange attractor'
      near to the postero-external wall of the bulb. CONCLUSIONS: The anatomical and
      kinematic complexity of the system, together with the irreversibility of the
      second Law of Thermodynamics, lead to a long-term tendency towards the appearance
      of a region of stagnant flow with increased Entropy in the territory of the
      strange attractor which determines--as an inevitable long-term outcome--the
      tendency to the appearance of atherosclerosis at this particular point.

PMID- 9528051
TI  - [Fatty diet and multiple sclerosis].
AB  - INTRODUCTION AND DEVELOPMENT: Multiple sclerosis (ME) is an inflammatory disease
      of the myelin of the central nervous system, the origin of which is still
      unknown. Genetic, infectious, immunological and environmental factors have all
      been blamed, but none of these factors on their own can explain the whole
      spectrum of this disease. Of the environmental factors, fat in the diet has given
      rise to most discussion. At the present time, it is known that polyunsaturated
      essential fatty acids form a part of biological membranes. A relationship has
      been found between the dietary fat consumed and the plasma levels and cell
      membrane content. CONCLUSIONS: The possible immuno-modulation function of these
      fatty acids justify rigorous evaluation of this hypothesis.

PMID- 9528052
TI  - [Lafora and neuropathology].
AB  - This article wants to be a memory to the figure and neuro-pathologic work of D.
      Gonzalo Rodriguez-Lafora. The tediousness of its neurological work allows to
      divide it in its slopes neurophatologic, neurophysiologic, clinic and therapy.
      Also, it embraces other topics outside of the field of the neurology, centered
      fundamentally in the psychiatry. It is without a doubt the facet neuro
      histopathologic the one that provides him bigger national and international
      prestige and it contributes to deepen in the histopathology of the senility,
      picking up in a definitive way in their work critical valuation of the
      discoveries histopathological in the senility (1952) their thought in this
      respect. Mention separated deserves its more important discovery: The inclusions
      amylaceous in cells ganglionars, in a certain type of epilepsy myoclonic that
      today takes its name. Other entities like the illness of Wernicke, the
      hemorrhages hipofisarias, the Parkinson (for scarce months he is not early to
      Levy in an important discovery), or the alterations of the malaria in the
      cerebral fabric plows object of their attention, of the work of Lafora highlights
      its anatomo-pathologics works next to figures as Kraepelin, Alzheimer, Vogt,
      Openheim or Brodmann. Professor Lafora's figure is known internationally as
      neuropathologist, recognizing its contribution, collection in the world
      literature, to the study of the myoclonic epilepsy: 'Lafora disease. A form of
      progressive myoclonus epilepsy.

PMID- 9528053
TI  - [A 74-year-old woman with fever, pain and limb weakness].

PMID- 9528054
TI  - [Design of a non-verbal method of communication using cartoons].
AB  - INTRODUCTION: Nursery care to patients with serious disorders of language
      expression is complex and arises nervousness in the patient, his relatives and in
      the professionals caring for him. OBJECTIVE: Our aim has been to design a number
      of drawings which allow us to improve our ability to connect with patients
      suffering from serious disorders of verbal language. MATERIAL AND METHODS: We
      have applied a booklet of drawings, representing the most common needs of this
      kind of patients, to a group of 34 patients affected of severe dysarthria or
      motor aphasia. RESULTS: Most of our patients have used this booklet to express
      their basic needs and that has resulted in a lower degree of anxiety in these
      patients. CONCLUSIONS: Our intention was not to design a new language but to use
      a very simple form of language, visual language, to standardize the most basic
      communication with patients affected of severe language disorders. We invite
      other groups on neurological nursing in our country to use this strategy so as to
      connect with their patients.

PMID- 9528056
TI  - [Multiple dural empyemas].

PMID- 9528055
TI  - [Occlusion of the right middle cerebral artery in a man with polycythemia vera].

PMID- 9528058
TI  - [Hallevorden-Spatz disease].

PMID- 9528057
TI  - [Disorder of vertical conjugate gaze secondary to a bilateral thalamic infarct
      which occurred during an attack of migraine].

PMID- 9528059
TI  - [Acute cerebellar syndrome due to 5-fluorouracil].

PMID- 9528060
TI  - [Posterior fracture-dislocation of both shoulders following a convulsive seizure.
      A case report].

PMID- 9528061
TI  - [Atypical morphological evolution of an intracerebral hematoma].

PMID- 9528062
TI  - [Epidemiological study of head injuries seen in the Tortosa health district].

PMID- 9528063
TI  - [Null husband-wife concordance of Parkinson's disease in 1,000 married couples
      over 50 years of age].

PMID- 9528064
TI  - [Anemia in a patient with cerebrovascular hemorrhagic accident].

PMID- 9528065
TI  - [Tardive dystonia following the administration of clebopride].

PMID- 9528066
TI  - [Peripheral 'man in a barrel' syndrome].

PMID- 9528067
TI  - [Insomnia during treatment with amantadine].

PMID- 9528068
TI  - [Gonzales-Montalvo word accentuation test in a healthy population].

PMID- 9528069
TI  - [Gonzales-Montalvo word accentuation test: analysis of a group of patient with
      dementia].

PMID- 9528070
TI  - [Craniosynostosis and papilledema].

PMID- 9528071
TI  - [Lesion of the external cutaneous branch of the right subcostal nerve following
      percutaneous liver biopsy].

PMID- 9528072
TI  - [Transient global amnesia: different etiopathogenic mechanisms].

PMID- 9528073
TI  - [Migraine with reversible unilateral mydriasis].

PMID- 9528074
TI  - [Fatigue in chewing as the initial symptom of myasthenia gravis in a 81-year-old
      woman].

PMID- 9528075
TI  - [Chronic adhesive arachnoiditis following epidural paramethasone].

PMID- 9528076
TI  - [Prevalence of myasthenia gravis on the island of La Palma].

PMID- 9528077
TI  - [Idiopathic multiple cerebral hemorrhage: are platelet anti-aggregation agents a
      risk factor?].

PMID- 9528079
TI  - [Neuroepithelial cyst of the choroid sulcus as a probable cause of symptomatic
      focal epilepsy].

PMID- 9528078
TI  - [Myasthenia gravis and Pneumocystis carinii pneumonia].

PMID- 9528080
TI  - [Health and finances].

PMID- 9528081
TI  - [Leukoencephalopathy: the frontier between what is reversible and what is
      persistent].

PMID- 9528082
TI  - [Hypersomnia and alteration of vertical gaze in two young patients].

PMID- 9528083
TI  - [Convulsions in the seriously ill patient].

PMID- 9528084
TI  - [Historical analysis of the work of Charcot].

PMID- 9528086
TI  - [The Spanish language under attack].

PMID- 9528085
TI  - [Telematics and neurology].

PMID- 9528087
TI  - [In defense of psychoanalysis].

PMID- 9528088
TI  - [Prognostic factors in subarachnoid hemorrhage].

PMID- 9528089
TI  - [Primary intraventricular hemorrhage].

PMID- 9528090
TI  - [Electrical status epilepticus during sleep and benign partial epilepsy with
      Rolandic paroxysms].

PMID- 9528091
TI  - [Pathogenesis of hallucinations].

PMID- 9528093
TI  - [Quo vadis Neurosurgery?].

PMID- 9528092
TI  - [Whither neurosurgery?].

PMID- 9528095
TI  - [Early infantile epileptic encephalopathy (Ohtahara syndrome)].

PMID- 9528094
TI  - [Nicardipine and migraine].

PMID- 9528096
TI  - [The contents of neurological publications].

PMID- 9528097
TI  - Non-linear elution effects in split-peak chromatography. II. Role of ligand
      heterogeneity in solute binding to columns with adsorption-limited kinetics.
AB  - The split-peak effect is a useful phenomenon in studying the kinetic behavior of
      chromatographic supports. This work examined the combined role of ligand
      heterogeneity and non-linear elution conditions (i.e., sample load dependence) on
      the solute free fractions that are measured during split-peak studies. Exact
      expressions were derived to describe the effects of ligand heterogeneity under
      linear elution conditions, and simulation models were developed to specifically
      examine the combined effects of ligand heterogeneity and non-linear elution in
      systems with adsorption-limited rates for solute binding. The simulations showed
      that ligand heterogeneity increased the amount of free solute seen at any flow
      rate or sample size, with this being most noticeable when using low flow-rates or
      large samples. One application in which these increases were examined in detail
      concerned the use of the split-peak effect for association rate constant
      measurements. It was found that linear extrapolation methods developed for
      homogeneous systems (as a correction for non-linear elution conditions) could
      successfully be applied to columns containing heterogeneous ligands. Columns
      containing immobilized protein A and/or protein G were used as experimental
      models to test the validity of the simulations; the behavior of these columns
      showed good quantitative and qualitative agreement with the predicted theoretical
      results.

PMID- 9528098
TI  - Direct measurements of convective fluid velocities in superporous agarose beads.
AB  - Superporous agarose beads contain two sets of pores, diffusion pores and so
      called superpores or flow pores, in which the chromatographic flow can transport
      substances to the interior of each individual bead [Gustavsson and Larsson, J.
      Chromatogr. A 734 (1996) 231]. The existence of pore flow may be proven
      indirectly by the chromatographic performance of beads but it has never been
      directly demonstrated in a chromatographic bed. In this report, pore flow was
      directly measured by following the movement of micro-particles (dyed yeast cells)
      in a packed bed. The passage of the micro-particles through the superpores and
      through the interstitial pores was followed by a microscope/video camera focused
      on beads which were situated four layers from the glass wall. The video
      recordings were subsequently used to determine the convective fluid velocities in
      both the superpores and the interstitial pores. Experiments were carried out with
      three different bead size ranges, all of which contained superporous beads having
      an average superpore diameter of 30 microns. The superpore fluid velocity as % of
      interstitial fluid velocity was determined to be 2-5% for columns packed with 300
      500-micron beads (3% average value), 6-12% for columns packed with 180-300-micron
      beads (7% average value) and 11-24% for columns packed with 106-180-micron beads
      (17% average value). These data were compared to and found to agree with
      theoretically calculated values based on the Kozeny-Carman equation. In order to
      observe and accurately measure fluid velocities within a chromatographic bed,
      special techniques were adopted. Also, precautions were made to ensure that the
      experimental conditions used were representative of normal chromatography runs.

PMID- 9528099
TI  - Preparation of magnetic immobilized metal affinity separation media and its use
      in the isolation of proteins.
AB  - A new method of pseudobiospecific protein isolation is developed and tested,
      which employs both metal affinity and magnetism as the basis for isolation. The
      chelating group iminodiacetic acid (IDA) has been coupled to the surface of
      magnetic agarose, and when charged with metal ions (Cu2+ or Zn2+) is capable of
      binding model proteins which display metal affinity, and of separating protein
      mixtures. Magnetic properties of the medium facilitated the batch recovery of the
      adsorbent, as losses are minimized by concentrating and retaining the separation
      medium with the aid of a magnet. Model proteins were used to characterize protein
      adsorption, capacity, and stability of IDA magnetic agarose. Recovery from a cell
      lysate was demonstrated by protein isolation from extracts of E. coli containing
      a target protein. Overall, this study effectively illustrates the engineering of
      separation media which combine several desired properties for the development of
      a new branch of metal affinity-based bioseparation.

PMID- 9528100
TI  - Determination of glycolic acid in cosmetic products by solid-phase extraction and
      reversed-phase ion-pair high-performance liquid chromatography.
AB  - A procedure has been developed for the assay of glycolic acid in cosmetic
      products by reversed-phase high-performance liquid chromatography using an ion
      pairing method. After dissolution in tetrahydrofuran-water (90:10, v/v), samples
      were purified by solid-phase extraction using silica-based strong anion-exchange
      cartridges and analysed directly on an Ultrasphere ODS column with UV detection
      at 210 nm and methanol-phosphate buffer (2:98, v/v), containing
      tetrabutylammonium iodide, as the mobile phase. Recovery of glycolic acid from
      different cosmetic matrices was between 92.4 and 96.2% and the precision of the
      method was better than 5.4% relative standard deviation. The procedure is rapid,
      simple, selective and it is suitable for routine analyses of commercial
      cosmetics.

PMID- 9528101
TI  - Identification of eicosanoids in the red algae, Gracilaria asiatica, using high
      performance liquid chromatography and electrospray ionization mass spectrometry.
AB  - Identification of eicosanoids which are metabolites of arachidonic acid in red
      algae Gracilaria asiatica, one of the popular seaweeds in Japan, was carried out
      using high-performance liquid chromatography (HPLC) interfaced with electrospray
      ionization mass spectrometry. Prostaglandin (PG) E2, 15-keto-PGE2, and 8
      hydroxyeicosatetraenoic acid (HETE) were detected as major eicosanoids and PGA2,
      leukotriene B4 as minor ones in G. asiatica. 8- and 12-HETE had the same
      retention time in HPLC analysis, but using this analytical method, we were able
      to identify them.

PMID- 9528102
TI  - Effect of the hydrolysis method on the determination of the amino acid
      composition of proteins.
AB  - Fast and reproducible separation and determination of amino acids serves the
      economical and reliable characterization and quantification of peptides and
      proteins as well as the identification of proteins by amino acid composition
      analysis on a large-scale. A prerequisite of a successful compositional analysis
      is a complete hydrolysis of the peptides and proteins and a quantitative recovery
      of the residues in the hydrolyzate. We investigated the effect of different acid
      hydrolysis methods on the compositional analysis of known proteins in solution
      and after blotting onto polyvinylidene difluoride membranes and worked out the
      conditions for the processing of large numbers of samples. The reliability of
      each method was studied by introducing the analysis data into the AACompIdent
      software and deducing the protein identification scores. All acid-hydrolysis
      methods delivered reliable analysis data. The most accurate data were provided by
      conventional, thermal hydrolysis of proteins in solution in the presence of
      methanesulfonic acid, closely followed by hydrolysis with hydrochloric acid and
      microwave radiation-dependent hydrolysis with hydrochloric or methanesulfonic
      acid, respectively. For blotted proteins, conventional hydrolysis delivered more
      accurate analysis data in comparison with the microwave radiation-induced
      hydrolysis. The extraction of the residues from the membrane hydrolyzate was a
      critical step for unambiguous protein identification. Microwave radiation-induced
      hydrolysis was responsible for a higher degree of racemization of the residues.

PMID- 9528103
TI  - Bovine whey fractionation based on cation-exchange chromatography.
AB  - Bovine whey proteins have potential applications in veterinary medicine, food
      industry and as supplements for cell culture media. A fractionation scheme for
      the economically interesting proteins, such as IgG, lactoferrin and
      lactoperoxidase, based on cation exchangers was the goal of our investigations. A
      chromatographic process was developed where alpha-lactalbumin passes through the
      column and separation of the desired proteins is achieved. Four different cation
      exchange media (S-HyperD-F, S-Sepharose FF, Fractogel EMD SO3- 650 (S) and Macro
      Prep High S Support) were compared in regard to their dynamic binding capacity
      for IgG and their different elution behaviours when sequential step gradients
      with NaCl buffers were applied. Peak fractions were analyzed by size-exclusion
      chromatography and sodium dodecyl sulphate-polyacrylamide gel electrophoresis.
      Lactoperoxidase activity was monitored by the oxidation of o-phenylenediamine. In
      order to explain the different resolution behaviours, isocratic runs with pure
      standards of whey proteins were performed. The k' values were calculated and
      plotted against salt concentration. Fractogel EMD had the highest binding
      capacity for IgG, 3.7 mg/ml gel at a linear flow-rate of 100 cm/h, but the
      resolution was low compared to that with the other three media. S-Hyper D and S
      Sepharose FF showed lower capacities, 3.3 and 3.2 mg/ml gel, respectively, but
      exhibited better protein resolution. These effects could be partially explained
      by the k' versus salt concentration plots. The binding capacity of Macro-Prep S
      was considerably lower compared to that of the other resins investigated because
      its selectivity for whey proteins was completely different. S-Sepharose FF and S
      Hyper D combine relatively high dynamic capacity for IgG and good resolution.
      Compared to studies with standard proteins, such as 100 mg/ml bovine serum
      albumin for S-Hyper D, their binding capacities were very low. Even after removal
      of low-molecular-mass compounds, the capacity could not be improved
      significantly. The running conditions (low pH) were responsible for the low
      protein binding capacity, since low-molecular-mass compounds in the feed do not
      compete with the adsorption of whey protein. The dynamic capacity did not
      decrease to a large extent within the range of flow-rates (100-600 cm/h)
      investigated. The dynamic capacity of HyperD and Fractogel was at least five
      times higher when pure bovine IgG was used for determination. In conclusion, S
      Sepharose FF, S-Hyper D-F and Fractogel EMD SO3- 650 (S) are considered as
      successful candidates for the large-scale purification of bovine whey proteins.

PMID- 9528104
TI  - Determination of trichothecene mycotoxins in wheat by use of supercritical fluid
      extraction and high-performance liquid chromatography with diode array detection
      or gas chromatography with electron capture detection.
AB  - The extraction behaviour of the Fusarium mycotoxin deoxynivalenol (DON) and some
      related type B trichothecenes from spiked seasand, spiked wheat flour and
      naturally contaminated wheat flour with modified supercritical CO2 has been
      investigated and optimized under several conditions. The extraction fluid was
      decompressed over a solid-phase trap and the amount of deposited analytes was
      determined by HPLC-diode array detection (DAD) or GC-electron capture detection
      (ECD) without any further clean-up. Recovery rates as high as 90.1 +/- 10.7% were
      achieved for spiked wheat samples and 53.0 +/- 3.2% for naturally contaminated
      samples. The performance of the optimized supercritical fluid extraction (SFE)
      method was compared with an already well established analytical method employing
      extraction on a rotary shaker in combination with Mycosep clean-up. Moreover, the
      SFE procedure developed for naturally DON contaminated wheat was employed for the
      simultaneous extraction of 5 type B trichothecenes by GC-ECD. This work
      represents the first successful approach in obtaining an SFE-method for the
      extraction of Fusarium mycotoxins from wheat with reasonable recoveries and good
      precision.

PMID- 9528105
TI  - Inter-laboratory validation of solid-phase microextraction for the determination
      of triazine herbicides and their degradation products at ng/l level in water
      samples.
AB  - The accuracy and precision of solid-phase microextraction (SPME) were validated
      in an inter-laboratory study including ten laboratories for the analysis of
      triazine herbicides and their metabolites at ng/l level in aqueous samples. The
      SPME conditions were optimised in order to obtain maximum sensitivity.
      Especially, salt addition and choice of the SPME fibre coated with Carbowax
      divinylbenzene increased the sensitivity. The average detection limits were in
      the range from 4 to 24 ng/l for the triazine herbicides, and 20 and 40 ng/l for
      desisopropylatrazine and desethylatrazine, respectively. The average r2 values of
      the calibration curves were above 0.99 for all of the analytes. The statistical
      data treatment was performed in accordance with the International Standardisation
      Organisation (ISO) standard 5725. Relative repeatability standard deviations
      between 6 and 14% and relative reproducibility standard deviations between 10 and
      17% were found. The determined concentrations of the reference sample compared
      well to the "true" values, thus proving the good accuracy of the method. It is
      concluded that SPME is a reliable technique for the quantitative analysis of
      water samples containing triazine herbicides in concentrations around the
      European limit of 100 ng/l for individual pesticides in drinking water.

PMID- 9528107
TI  - Analysis of traditional Chinese anticancer drugs by capillary electrophoresis.
AB  - The results reported in this communication demonstrate that capillary zone
      electrophoresis (CZE) can be used easily for the quantitative determination of
      the potential anticancer drugs berberine and isoguanosine in the extract of the
      traditional Chinese medicinal herb. Isoguanosine and berberine can be monitored
      selectively and sensitively at 254 nm within 14 min in the plant extract using a
      100-mM sodium citrate running buffer (adjusted to pH 2.7; applied voltage 12 kV).
      The concentration range of 0.1-50 micrograms ml-1 proved to be sufficient for
      exact quantification and the peak profile showed good reproducibility [relative
      standard deviations (n = 32); for the migration time 0.22% (isoguanosine) and
      1.32% (berberine); for the peak area 2.8% (isoguanosine) and 3.2% (berberine)].
      The measured concentrations in the crude extract were 1.3 micrograms ml-1 for
      isoguanosine and 8.7 micrograms ml-1 for berberine. In addition to the better
      separation performance, CZE shows several other remarkable advantages over high
      performance liquid chromatography (HPLC), such as rapidity of analysis, small
      sample volume, no requirement of organic solvent in the running buffer and low
      cost of reagents.

PMID- 9528106
TI  - Determination of vitamin B6 (pyridoxamine, pyridoxal and pyridoxine) in pork meat
      and pork meat products by liquid chromatography.
AB  - A liquid chromatographic method for determining vitamin B6 compounds in pork meat
      and pork meat products is examined. It uses the same extraction procedure as that
      applied for thiamin and riboflavin determination, followed by a liquid
      chromatographic separation on a reversed-phase C18 column with 0.01 M H2SO4 as
      mobile phase at 30 degrees C. 4-Deoxypyridoxine is used as internal standard. The
      analytical parameters linearity, precision of the method (R.S.D. = 7.3 and 6.9%
      for pyridoxamine and pyridoxal, respectively) and accuracy obtained by recovery
      assays (99 and 85.1% for pyridoxamine and pyridoxal, respectively) show that the
      studied method is useful to measure these compounds in pork meat.

PMID- 9528108
TI  - Bat sonar: an alternative interpretation of the 10-ns jitter result.
AB  - In 1990 Simmons et al. reported evidence of a time resolution hitherto unknown in
      any animal, namely a 10-ns jitter detection threshold in echolocating bats. This
      result is discussed. The calibration data from the original papers are examined.
      Observations indicating other cues than delay being presented to the bats are
      given. We offer an alternative explanation for the psychometric jitter function,
      based on the assumption of a subtle distortion due to impedance mismatch in the
      delay-producing apparatus. We also report that effects of impedance mismatch are
      detectable by a human subject in a model experiment.

PMID- 9528109
TI  - A comparative study of hearing ability in fishes: the auditory brainstem response
      approach.
AB  - Auditory brainstem response (ABR) techniques, an electrophysiological far-field
      recording method widely used in clinical evaluation of human hearing, were
      adapted for fishes to overcome the major limitations of traditional behavioral
      and electrophysiological methods (e.g., invasive surgery, lengthy training of
      fishes, etc.) used for fish hearing research. Responses to clicks and tone bursts
      of different frequencies and amplitudes were recorded with cutaneous electrodes.
      To evaluate the effectiveness of this method, the auditory sensitivity of a
      hearing specialist (goldfish, Carassius auratus) and a hearing generalist (oscar,
      Astronotus ocellatus) was investigated and compared to audiograms obtained
      through psychophysical methods. The ABRs could be obtained between 100 Hz and
      2000 Hz (oscar), and up to 5000 Hz (goldfish). The ABR audiograms are similar to
      those obtained by behavioral methods in both species. The ABR audiogram of
      curarized (i.e., Flaxedil-treated) goldfish did not differ significantly from two
      previously published behavioral curves but was lower than that obtained from
      uncurarized fish. In the oscar, ABR audiometry resulted in lower thresholds and a
      larger bandwidth than observed in behavioral tests. Comparison between methods
      revealed the advantages of this technique: rapid evaluation of hearing in
      untrained fishes, and no limitations on repeated testing of animals.

PMID- 9528110
TI  - Effects of transition metal ions on spontaneous electrical activity and chemical
      synaptic transmission of neurons in the medicinal leech.
AB  - Leech neurons exposed to salines containing inorganic Ca(2+)-channel blockers
      generate rhythmic bursts of impulses. According to an earlier model, these
      blockers unmask persistent Na+ currents that generate plateau-like
      depolarizations, each triggering a burst of impulses. The resulting increase in
      intracellular Na+ activates an outward Na+/K+ pump current that contributes to
      burst termination. We tested this model by examining systematically the effects
      of six transition metal ions (Co2+, Ni2+, Mn2+, Cd2+, La3+, and Zn2+) on the
      electrical activity of neurons in isolated leech ganglia. Each ion induced
      bursting activity, but the amplitude, form, and persistence of bursting differed
      with the ion used and its concentration relative to Ca2+. All ions tested
      suppressed chemical synaptic transmission between identified motor neurons,
      consistent with block of voltage-dependent Ca2+ currents in these cells. In
      addition, a strong correlation between suppression of synaptic transmission and
      burst amplitudes was obtained. Finally, burst duration was increased and the rate
      of repolarization decreased in reduced K+ saline, as expected for pump-dependent
      repolarization. These results provide further support for the hypothesis that a
      novel form of oscillatory electrical activity driven by persistent Na+ currents
      and the Na+/K+ pump occurs in leech ganglia exposed to Ca(2+)-channel blockers.

PMID- 9528111
TI  - A description of the ontogeny of mouse agonistic behavior.
AB  - The development of agonistic behavior was characterized in outbred Swiss CD-1
      male Mus domesticus. At weaning (postnatal day [PND] 21), mice were housed either
      individually or as male pairs. Social encounters were carried out between dyads
      of initially unfamiliar same-age and same-housing subjects every 3rd day, from
      PND 23 to 47. The majority of both offensive and defensive elements had their
      onset around PND 29. Overall, their expression increased around puberty (i.e., on
      PND 35), which also represented the peak of an inverted U-shaped profile for the
      frequency of the "ambivalent" tail rattling behavior. A stability of dominance
      submission relationships over development appeared, and early short latencies to
      display either the first crouched posture (subordinate) or the first attack
      (dominant) turned out to be possible predictors of adult social status. Ongoing
      individual housing was associated with a greater expression and an earlier onset
      of fighting behavior.

PMID- 9528112
TI  - Pavlovian conditioning of social-affiliative behavior in the Mongolian gerbil
      (Meriones unguiculatus).
AB  - Gerbils learned to approach a spatial-olfactory stimulus that signaled access to
      their pairmate. Experiments 1 and 3 used a discrimination procedure in which 1
      conditioned stimulus (the CS+) was presented immediately before access to the
      pairmate and another (the CS-) was presented alone. Both male and female gerbils
      came to approach the CS+ sooner than the CS- and spent more time near the CS+
      than the CS-. Discrimination learning was facilitated by making the CS+ and CS-
      spatially distinct (Experiment 3). Learning also was demonstrated in male
      gerbils, using a between-subjects design with a single CS. Pairing the CS with
      the opportunity for social interaction resulted in greater approach to the CS
      within 10 trials than presenting the CS and social opportunity in an unpaired
      fashion (Experiment 2). These findings demonstrate social-affiliative learning in
      the Mongolian gerbil. Similarities and differences between these findings and
      sexual conditioning effects in other species are discussed.

PMID- 9528113
TI  - Detection of changes in timbre and harmonicity in complex sounds by zebra finches
      (Taeniopygia guttata) and budgerigars (Melopsittacus undulatus).
AB  - Thresholds for detecting alterations in the timbre and harmonicity of complex
      harmonic signals were measured in zebra finches, budgerigars, and humans. The
      stimuli used in this experiment were designed to have particular salience for
      zebra finches by modeling them after natural zebra finch calls. All 3 species
      showed similar abilities for detecting an amplitude decrement in a single
      component of a harmonic complex. However, zebra finches and budgerigars were
      extraordinarily sensitive to the mistunings of single harmonics and exhibited
      significantly lower thresholds compared with humans at 2 different fundamental
      frequencies, 570 Hz and 285 Hz. Randomizing relative phases of components in a
      harmonic stimulus resulted in a significant increase in threshold for detecting
      mistunings in zebra finches but not in humans. Decreasing the duration of
      mistuned harmonic stimuli resulted in higher thresholds for both birds and
      humans. The overall superiority of birds in discriminating inharmonicity suggests
      that birds and mammals may use different strategies in processing these complex
      harmonic sounds.

PMID- 9528114
TI  - Bipedal posture and hand preference in humans and other primates.
AB  - Hand preference for quadrupedal and bipedal reaching in humans and rhesus
      macaques (Macaca mulatta) was examined, and the data were compared with postural
      reaching data that have been reported for 8 other primate species. Population
      level biases were found toward use of the right hand for quadrupedal and bipedal
      reaching in humans and use of the left hand for quadrupedal reaching in rhesus
      macaques. Rhesus macaques showed a significant shift toward greater use of the
      right hand for bipedal vs. quadrupedal reaching. Comparisons with other species
      showed significant variance in the direction and strength of hand preference
      across reaching postures. The study noted right-hand biases for bipedal reaching
      in humans, great apes, and tufted capuchins and shifts toward greater use of the
      right hand for bipedal vs. quadrupedal reaching in great apes, tufted capuchins,
      and rhesus macaques. These results suggest that posture alters both the direction
      and strength of primate hand preference and that bipedalism may have facilitated
      species-typical right-handedness in humans.

PMID- 9528115
TI  - Anticipation of play elicits high-frequency ultrasonic vocalizations in young
      rats.
AB  - The authors provide initial documentation that juvenile rats emit short, high
      frequency ultrasonic vocalizations (high USVs, approximately 55 kHz) during rough
      and-tumble play. In an observational study, they further observe that these
      vocalizations both correlate with and predict appetitive components of the play
      behavioral repertoire. Additional experiments characterized eliciting conditions
      for high USVs. Without prior play exposure, rats separated by a screen vocalized
      less than playing rats, but after only 1 play session, separated rats vocalized
      more than playing rats. This findings suggested that high USVs were linked to a
      motivational state rather than specific play behaviors or general activity.
      Furthermore, individual rats vocalized more in a chamber associated with play
      than in a habituated control chamber. Finally, congruent and incongruent
      motivational manipulations modulated vocalization expression. Although play
      deprivation enhanced high USVs, an arousing but aversive stimulus (bright light)
      reduced them. Taken together, these findings suggest that high USVs may index an
      appetitive motivation to play in juvenile rats.

PMID- 9528116
TI  - Hearing and vocalizations of wild-caught Australian budgerigars (Melopsittacus
      undulatus).
AB  - This study examined the hearing and contact calls of wild-caught Australian
      budgerigars (Melopsittacus undulatus) and compared these data to hearing and
      vocalizations in the much more extensively studied domesticated budgerigar. The
      spectral energy in the contact calls of both wild-caught and domesticated
      budgerigars falls almost exclusively in the frequency of 2-4 kHz. Absolute and
      masked thresholds were similar in both groups of birds. Similar to the results
      found in domesticated birds, critical ratio functions for the wild-caught
      budgerigars decreased at frequencies of 1.0 kHz-2.86 kHz and then increased again
      dramatically at frequencies above 2.86 kHz.

PMID- 9528117
TI  - Pregnancy block in house mice (Mus domesticus) as a function of t-complex
      genotype: examination of the mate choice and male infanticide hypotheses.
AB  - Pregnancy block, whereby recently mated female mice abort their pregnancies when
      exposed to novel (strange) males, was studied in house mice (Mus domesticus)
      differing in t-complex genotype; t-mutations are deleterious and +/t females
      avoid +/t males as mates. The results of Experiment 1, in which the genotype of
      the female, stud male, and strange male was systematically varied, showed that
      pregnancy block was most frequent when the strange male was +/+. Because this
      effect was not enhanced among +/t females when stud males were +/t, the results
      cannot clearly be explained by the hypothesis that pregnancy block is a
      manifestation of mate choice. Moreover, the "strange male" effect in Experiment 1
      is unlikely to be a female response correlated with the risk of male infanticide,
      as +/+ and +/t males did not differ in their infanticidal tendencies (Experiments
      2 & 3). Alternative hypotheses, including a modified version of the mate choice
      hypothesis, are discussed.

PMID- 9528119
TI  - Backwards bifurcations and catastrophe in simple models of fatal diseases.

PMID- 9528118
TI  - Hand use and gestural communication in chimpanzees (Pan troglodytes).
AB  - Hand use in gestural communication was examined in 115 captive chimpanzees (Pan
      troglodytes). Hand use was measured in subjects while they gestured to food
      placed out of their reach. The distribution of hand use was examined in relation
      to sex, age, rearing history, gesture type, and whether the subjects vocalized
      while gesturing. Overall, significantly more chimpanzees, especially females and
      adults, gestured with their right than with their left hand. Foods begs were more
      lateralized to the right hand than pointing, and a greater prevalence of right
      hand gesturing was found in subjects who simultaneously vocalized than those who
      did not. Taken together, these data suggest that referential, intentional
      communicative behaviors, in the form of gestures, are lateralized to the left
      hemisphere in chimpanzees.

PMID- 9528120
TI  - Production of OH-radical-type oxidant by lucigenin.
AB  - In the presence of NADH- reductases (dihydrolipoamide: NAD oxidoreductase E.
      C.1.8.1.4 from pig heart or from Clostridium kluyveri; frequently also addressed
      as "diaphorases") and NADH lucigenin strongly increases ethylene production from
      a-keto-methylthiobutyrate (KMB) as an indicator for strong oxidants of the OH
      radical type. These reactions are further stimulated in the presence of Fe3+
      ions. With these NADH-"diaphorases", the structurally similar poison, paraquat,
      in the absence or presence of Fe3+ has no effect. With ferredoxin-NADP reductase
      (E. C.1.18.1.2.), however, paraquat reacts quasi identical to lucigenin.
      Superoxide dismutase, catalase, free radical- or OH-scavengers such as mannitol,
      propylgallate, DABCO, and desferal inhibit the reaction whereas EDTA (in the
      presence or absence of added Fe3+) is stimulatory. From these data we conclude
      that the superoxide--indicator LUC is redox-active after unspecific coupling to
      several almost ubiquitory NAD(P)H- reductases catalyzing monovalent oxygen
      reduction. Lucigenin thus should no longer be used as a "specific" superoxide
      indicator. This report is in agreement with very recent results by Liochev and
      Fridovich (Arch. Biochem. Biophys. 337, 115 [1997]) and Vasquez-Vivar et al.
      (FEBS Lett. 403, 127 (1997).

PMID- 9528121
TI  - The Rieske protein from purple sulfur bacteria is an extrinsic protein.
AB  - The mode of membrane attachment of the Rieske iron-sulfur protein from cytochrome
      bc1 complex of Rhodospirillum rubrum has been studied using biochemical
      approaches. In contrast to cytochrome c1 the bacterial Rieske protein was
      extracted from chromatophores using chaotropic agents (NaSCN, urea, guanidine),
      an alkaline pH and relatively low concentration of Triton X-100. The results
      presented here lead to the conclusion, that the Rieske protein from
      chromatophores is extrinsic and that their association with the rest of the
      complex involves hydrophobic interactions.

PMID- 9528122
TI  - A new inhibitor of synovial phospholipase A2 from fermentations of Penicillium
      sp. 62-92.
AB  - Penidiamide, a new tripetide containing dehydrotryptamine, glycine and
      anthranilic acid linked together by two amide bonds, and oxindole were isolated
      from submerged cultures of Penicillium sp. 62-92. Both compounds preferentially
      inhibited human synovial phospholipase A2, penidiamide with an IC50 of 30 microM
      and oxindole of 380 microM. With the exception of U 937 cells (leukemia, human),
      no cytotoxic activities were detected against HL-60- (leukemia, human), HeLa S3-
      (epitheloid carcinoma, human), BHK 21- (kidney fibroblasts, hamster), and L1210
      cells (leukemia, mouse). No antimicrobial activity was detected for oxindole, and
      only weak antibacterial activity for penidiamide. The structure of penidiamide
      was elucidated by spectroscopic methods.

PMID- 9528123
TI  - Ribosomal RNA gene restriction fragment diversity amongst Penner serotypes of
      Campylobacter jejuni and Campylobacter coli.
AB  - Diversity based on ribosomal RNA gene-restriction endonuclease digest patterns
      was detected amongst forty-seven strains of Campylobacter made up of 38 strains
      of Campylobacter jejuni and 9 strains of Campylobacter coli. Restriction digests
      of chromosomal DNA prepared by treating with Hae III were probed with an
      oligonucleotide specific for Campylobacter 16S ribosomal RNA genes. Seventeen
      distinct hybridization patterns, each indicating the presence of 2-4 copies of
      the 16S rRNA gene are encoded in Campylobacter DNA. Differences in fragment
      patterns were observed not only between members of two species, but also between
      individual strains of the same species. Ribopattern fragments of 8.71, 7.56, 2.81
      and 1.0 kb were characteristic of the majority of C. jejuni, whereas 7.59 and
      4.68 kb fragments were commonly present in C. coli. In conclusion, Hae III
      ribotyping was even more discriminatory than the Penner serotyping of C. jejuni
      and C. coli, as strains of the same serotype were distinguished.

PMID- 9528124
TI  - DNA-probing for genes coding for denitrification, N2-fixation and nitrification
      in bacteria isolated from different soils.
AB  - Bacteria isolated from different layers of four soils of the Cologne area were
      analyzed for denitrifying, nitrifying and N2-fixing isolates by colony
      hybridization using gene probes. In the soils tested, the percentage of
      denitrifying bacteria among the total population isolated was 3-8% (in one case
      exceptionally 15%) and thus small. Denitrifying bacteria were particularly
      enriched in the upper layer (depth approximately 5 cm) and were present only in
      low amounts at 25 cm depth in two gleysol soils. Nitrate apparently did not
      determine the distribution of denitrifying bacteria in these soils. The potential
      denitrification activity of different soil layers coincided with the distribution
      pattern of isolates assessed by DNA-probing. The total number of bacteria and of
      denitrifying isolates was considerably higher in or at the roots of plants than
      in the bulk, root-free soil adjacent to the plants. The percentage of the
      isolated aerobic N2-fixing bacteria varied between 0-3%, and these bacteria could
      be isolated mainly from the upper 5 cm layer. A small portion of the isolates
      hybridized with the probe coding for part of one subunit of ammonia monooxygenase
      from Nitrosomonas europaea. The investigation showed that DNA-probing can provide
      useful information about the relative distribution of denitrifying and N2-fixing
      bacteria in different soils and their layers.

PMID- 9528125
TI  - Anti-oxidant mechanisms involved in gastroprotective effects of quercetin.
AB  - The anti-ulcerogenic and anti-oxidant effects of various flavonoids have been
      frequently reported. We investigated the cytoprotective properties of quercetin,
      a natural flavone, in gastric mucosal injury induced by 50% ethanol, since in
      this experimental model the pathogenesis of the lesions has been related with
      production of reactive oxygen species. The involvement of neutrophil infiltration
      and the capacity of this flavonoid to restrain the oxidative process produced in
      the gastric tissue after ethanol administration were also investigated. Oral
      pretreatment with the highest dose of quercetin (200 mg/kg), 120 min before
      absolute ethanol was the most effective anti-ulcer treatment. Thiobarbituric acid
      reactive substances in the gastric mucosa, an index of lipid peroxidation, were
      increased by ethanol injury, but the increase was inhibited by the administration
      of 200 mg/kg of quercetin. This dose also induced a significant enhancement in
      the levels of mucosal non-protein SH compounds (important anti-oxidant agents)
      and in glutathione peroxidase activity. Exposure of the gastric mucosa to 50%
      ethanol induced a significant increase in myeloperoxidase activity, an index of
      neutrophil infiltration. However, quercetin was not able to modify the increase
      in enzymatic activity generated by the necrotizing agent. The activity of
      superoxide dismutase enzyme involved in several antioxidant processes was also
      not significantly modified after quercetin treatment. These results suggest that
      the anti-ulcer activity of quercetin in this experimental model could be partly
      explained by the inhibition of lipid peroxidation, through decrease of reactive
      oxygen metabolites. However, the inhibition of neutrophil infiltration or the
      increase of superoxide dismutase activity does not appear to be involved in
      gastroprotective effect of this flavonoid.

PMID- 9528126
TI  - Nitidon, a new bioactive metabolite from the basidiomycete Junghuhnia nitida
      (Pers.: Fr.) Ryv.
AB  - Nitidon, a highly oxidised pyranone derivative produced by the basidiomycete
      Junghuhnia nitida, has been isolated and its biological activities evaluated. The
      structure was determined by spectroscopic methods. Nitidon exhibits antibiotic
      and cytotoxic activities and induces morphological and physiological
      differentiation of tumor cells at nanomolar concentrations.

PMID- 9528127
TI  - Does astaxanthin protect Haematococcus against light damage?
AB  - The photoprotective function of the ketocarotenoid astaxanthin in Haematococcus
      was questioned. When exposed to high irradiance and/or nutritional stress, green
      Haematococcus cells turned red due to accumulation of an immense quantity of the
      red pigment astaxanthin. Our results demonstrate that: 1) The addition of
      diphenylamine, an inhibitor of astaxanthin biosynthesis, causes cell death under
      high light intensity; 2) Red cells are susceptible to high light stress to the
      same extent or even higher then green ones upon exposure to a very high light
      intensity (4000 mumol photon m(-2)s(-1)); 3) Addition of 1O2 generators
      (methylene blue, rose bengal) under noninductive conditions (low light of 100
      mumol photon m(-2)s(-1) induced astaxanthin accumulation. This can be reversed by
      an exogenous 1O2 quencher (histidine); 4) Histidine can prevent the accumulation
      of astaxanthin induced by phosphate starvation. We suggest that: 1) Astaxanthin
      is the result of the photoprotection process rather than the protective; 2) 1O2
      is involved indirectly in astaxanthin accumulation process.

PMID- 9528128
TI  - Hemolytic activity of aminoethyl-dodecanoates.
AB  - The effect of new lysosomotropic compounds on red blood cell hemolysis and
      erythrocyte membrane fluidity has been investigated. In earlier studies it was
      shown that the compounds inhibit the growth of yeast and plasma membrane H(+)
      ATPase activity. The study was performed with eight aminoethyl esters of lauric
      acid variously substituted at nitrogen atom. Esters of dodecanoic acid were
      chosen for study because at that chain length dimethylaminoethyl esters showed
      maximum activity. The hemolytic activity of the substances studied exhibits
      diversified activity in their interaction with the erythrocyte membrane: they
      differ in hemolytic activity and affect membrane fluidity differently.
      Erythrocyte membrane fluidity changes under the effect of those compounds which
      possess highest hemolytic activity. The hemolytic activity of the aminoesters
      investigated was found to follow a sequence that depended on basicity (i.e.
      ability of the protonated form formation) of the compound and its polar head
      group size. The most active are the compounds that possess not more than four
      carbon atoms substituted at nitrogen and highest pKa value.

PMID- 9528129
TI  - The Glu-modification of alpha-tubulin in the feeding apparatus of the primitive
      flagellate Entosiphon sulcatum is only apparent after detergent treatment.
AB  - Using specific monoclonal antibodies, we investigated the distribution of post
      translational modified Tyr- and Glu-tubulins during interphase of the primitive
      flagellate Entosiphon sulcatum. Immunofluorescence studies of simultaneously
      permeabilized and fixed cells revealed that microtubular structures comprising
      Ca(2+)-labile subpellicular and flagellar MTs and Ca(2+)-stable MTs in the siphon
      complex (feeding organelle) reacted surprisingly unorthodox with antibodies
      against Tyr- and Glu-tubulin: Unexpectedly, the siphon complex consisting of
      Ca(2+)-stable MTs appeared exclusively Tyr-positive, whereas the Ca(2+)-labile
      subpellicular and flagellar MTs reacted with the Glu- as well as with the Tyr
      antibody. That the siphon MTs were indeed Ca(2+)-stable and all other MTs had
      become solubilized, was verified by EM-observation. This surprising result
      contrasting considerably with the permanent nature of the siphon complex, was
      reconsidered after preceding lysis and extraction procedures. Depending on the
      type of detergent used and on extraction times applied, the MTs of the siphon
      complex now always showed also Glu-positivity, indicating the presence of
      detyrosinated alpha-tubulin as a biochemical marker of stabilized MTs. Since
      saponin, irrespective of subsequent extraction times, always produced a Glu
      positive reaction and ultrastructural analysis never gave compelling evidence for
      a drastic MAP-removal, we conclude that the Glu-epitope became freely accessible
      due to conformational changes in the tubulin polymeres.

PMID- 9528130
TI  - Interaction of histone H1 with cis-platinum modified DNA.
AB  - Cis-diamminedichloroplatinum(II) (cis-DDP) is known as an effective anticancer
      drug. Its therapeutic effect is supposed to be a consequence of the covalent
      binding to DNA. A number of cellular proteins were found to bind selectively to
      DNA modified by cis-DDP (but not by its isomer trans-DDP). Here we present our
      observations on interaction of the linker histone H1 with cis- and trans-DDP
      modified DNA fragments. The results afford new experimental information about the
      preferential binding of histone H1 to cis-DDP-distorted DNAs versus trans-DDP
      modified ones.

PMID- 9528131
TI  - [Mastoid obliteration in open cavities].
AB  - The obliteration of a large or irregular mastoidectomy cavities with hard-to
      control areas is a common problem for ENT surgeons. Numerous obliteration
      techniques have been proposed in the last 50 years. We report our experience of
      obliteration of mastoid cavities in 74 ears using autogenous mastoid cortical
      bone chips and rib cartilage. Our procedure, a partial obliteration with
      meatoplasty, has yielded good results. Almost 92% of these ears were dry three
      years after surgery. There were no cases of recurrent cholesteatoma between bone
      chips.

PMID- 9528132
TI  - [Protruding jugular bulb. A review of 7 cases].
AB  - The position of the jugular bulb varies greatly. A high jugular bulb procident
      from the temporal bone is not uncommon. Most people with this anatomic variation
      remain asymptomatic. We report seven cases of high jugular bulb with clinical
      manifestations. The anatomy, clinical manifestations, diagnosis, and management
      are reviewed.

PMID- 9528133
TI  - [Auditory assessment in a protocol of concurrent carboplatin and irradiation use
      in fractionated therapy].
AB  - Possible ototoxicity related with a hyperfractionated concurrent chemo-radiation
      schedule was studied in 36 patients with head and neck cancer. The schedule
      consisted of two daily fractions, each consisting of 5 mg/m2 of carboplatin plus
      115 cGy. Therapy was given 5 days a week for 7 weeks up to a total dose of 700 mg
      carboplatin and 8050 cGy. Tonal audiograms and superliminal tests were carried
      out before treatment, at conclusion, six months post-treatment, and every year
      thereafter. After a mean follow-up of 18 months (maximum 30 months), no treatment
      related sensorineural hearing loss was observed. However, recruitment disappeared
      in post-treatment superliminal tests in 37% of patients who presented
      sensorineural deafness with recruitment, although it reappeared in audiograms
      recorded six months later. We attributed this to transient demyelinization. After
      treatment, a previous tympanosclerosis reactivated in 1 case and effusive otitis
      media occurred in 8 patients. Previous effusive otitis media disappeared in 1
      patient (nasopharyngeal tumor).

PMID- 9528135
TI  - [Rendu-Osler-Weber disease (hereditary hemorrhagic telangiectasia). Report of 30
      cases].
AB  - OBJECTIVE: To study the prevalence and modes of presentation of hereditary
      hemorrhagic telangiectasia (HHT) in Cantabria, Spain. MATERIALS AND METHODS: A
      retrospective study was made of all patients diagnosed as HHT in Cantabria in the
      last 20 years (1976-1995). The presence/absence of family history, recurrent
      nosebleed, mucosal and cutaneous telangiectasia, visceral involvement, and course
      of the disease were evaluated. RESULTS: Thirty patients ranging in age from 17 to
      75 years were diagnosed as HHT in the study period. Most of them had a family
      history of recurrent nasal bleeding. The main symptom was nosebleed. Pulmonary
      arteriovenous fistulas were found in 7 patients and gastrointestinal
      manifestations in 10 patients. Five patients died of complications directly
      attributable to the disease. CONCLUSIONS: The minimum prevalence of HHT in
      Cantabria is 1:12,200, Patients with recurrent nosebleed, particularly if a
      family history of epistaxis is present, should undergo exploration of the oral
      cavity for telangiectasia. Early diagnosis of HHT can help to avoid unnecessary
      diagnostic procedures and contribute to the early detection of associated
      visceral malformations. The treatment of HHT should be individualized.

PMID- 9528134
TI  - [Nasal sinus adenocarcinoma in patients exposed to wood dust in the Community of
      Cantabria, Spain].
AB  - OBJECTIVE: To study the incidence and clinical and histological features of
      sawdust-related nasosinusal adenocarcinoma (SRNA) in the Community of Cantabria.
      MATERIAL AND METHODS: A retrospective study was made of all patients diagnosed as
      SRNA in 9 years. RESULTS: Ten male patients, ranging in age from 56 to 64 years,
      were diagnosed as SRNA in this period. The most common location was the ethmoid.
      Histologically, six tumors were papillary and four were mucinous. Five patients
      received combined treatment (surgery and postoperative radiotherapy), one surgery
      alone, two radiotherapy, and one chemotherapy. The 5-year survival rate was
      28.5%. The most frequent cause of death was local recurrence. CONCLUSIONS: The
      incidence of SRNA in the Community of Cantabria is less than 0.2 cases per
      100,000 inhabitants/year. SRNA occurs almost exclusively in men and has an
      occupational origin. Papillary adenocarcinoma is the most frequent histological
      type. The treatment of choice is surgery associated with postoperative
      radiotherapy. The long-term prognosis is poor, so preventive measures to reduce
      exposure to sawdust are fundamental in risk groups.

PMID- 9528136
TI  - [Surgical pathology of parotid gland tumors].
AB  - The records of 27 patients operated for parotid tumors were reviewed
      retrospectively. Pleomorphic adenoma was the most frequent tumor (37.1%) and
      required subtotal parotidectomy in all cases. Twenty percent presented permanent
      facial paralysis of the marginal mandibular branch. No recurrence has been
      observed in five years of follow-up. Warthin's tumor, found in 11.1% of patients,
      was removed by either superficial or subtotal parotidectomy. Parotidean cysts
      were observed in 7.4% and were excised by superficial parotidectomy. The
      malignant tumors included squamous cell carcinoma (22.2%), adenoid cystic
      carcinoma (14.8%), melanoma (3.7%), and renal-cell metastasis (3.7%). All were
      treated by total parotidectomy with conservation of the facial nerve in 67%.
      Twenty-five percent had postoperative facial paralysis and 33% developed Frey's
      syndrome. Thirty-three percent died in the next 5 years from locoregional
      metastases.

PMID- 9528137
TI  - [Endoscopic approach to the treatment of subperiosteal orbital abscess].
AB  - The treatment of orbital complications of nasosinusal processes has seen numerous
      modifications. Traditionally, cases with purulent collections were treated by
      external drainage. Currently, the introduction of new optical systems allows such
      complications to be approached from within the nasal cavity. We report a case of
      a 3-year-old girl with a subperiosteal orbital abscess secondary to ethmoiditis,
      which was cured by minimally aggressive endoscopic management and medical
      treatment.

PMID- 9528138
TI  - [Bullous lesions of the larynx. A report of 2 cases].
AB  - Two cases of bullous disease of the larynx are presented, one located in skin and
      mucosa and the other in larynx. Clinical history, diagnostic procedures, and
      therapy are discussed. The patients were re-evaluated periodically for 1 and 2
      years, respectively, and they underwent periodic corticoid therapy. None of the
      severe complications described in the literature were observed in these patients.

PMID- 9528139
TI  - [Neuroendocrine carcinoma of the larynx].
AB  - We report a case of moderately differentiated neuroendocrine carcinoma arising in
      the left pyriform sinus and arytenoid of a 68-year-old man. The tumor was
      diagnosed initially as a poorly differentiated squamous carcinoma, but after
      surgery it gave rise to multiple painful skin metastases and a paraneoplastic
      syndrome. Immunocytochemical staining yielded the correct diagnosis. The patient,
      who had microscopic cervical lymph node metastases at the initial resection, died
      13 months later, thus confirming the poor prognosis of these tumors.

PMID- 9528140
TI  - [Minor salivary gland tumor in nasopharynx].
AB  - Pleomorphic adenoma, or mixed tumor, is the most common tumor of the salivary
      glands, being responsible for 47% of minor salivary-gland neoplasms. The palate
      is the most frequent location, but the nasopharynx is a rare site. The case of a
      64-year-old man diagnosed as pleomorphic adenoma of the nasopharynx is reported.
      The recent literature was reviewed and the anatomopathological and clinical
      features were analyzed, as well as the differential diagnosis.

PMID- 9528141
TI  - [Sarcomatous carcinoma versus malignant fibrohistiocytoma. Differential diagnosis
      of a case of cervical presentation].
AB  - A case is presented of cervical sarcomatoid carcinoma that was initially confused
      with malignant fibrohistiocytoma. The similarity in their histological features
      and compatible immunohistochemical tests make it necessary to include sarcomatoid
      carcinoma in the differential diagnosis malignant fibrohistiocytoma. Many
      atypical presentations of malignant fibrohistiocytoma may be true sarcomatoid
      carcinomas. Our case is special because the patient had a recent spinocellular
      carcinoma of the lip, in which the undifferentiated portion had originated lymph
      node metastasis.

PMID- 9528142
TI  - [Tracheostomy as a solution for subcutaneous emphysema and pneumomediastinum with
      severe respiratory failure].
AB  - Subcutaneous emphysema and pneumomediastinum have many causes. Generally they
      course without severe pathophysiological complications and severe respiratory
      complications are rare. However, cases with progressive dyspnea should be treated
      with tracheostomy or superficial incisions. A case is reported of a patient who
      underwent hip surgery under general anesthesia with tracheal intubation and later
      presented progressive dyspnea with subcutaneous emphysema and neuromediastinum.
      Tracheostomy yielded satisfactory results.

PMID- 9528144
TI  - [Methods of computer-assisted molecular modeling].
AB  - We present an overview on modern computer methods of molecular modelling. After
      treating three main steps of drug evaluation, namely target identification, lead
      identification and lead optimisation, we shortly discuss molecular graphics,
      molecular mechanics, molecular orbital and molecular dynamics methods. These are
      suitable for the more-or-less adequate modelling of real molecular processes both
      at the microscopic and the macroscopic levels. Molecular graphics provides
      beautiful pictures for the specialist that allow inspection and manipulation of
      detailed molecular models. An especially useful tool for the visualisation of
      molecular entities is the display of various properties on the molecular surface
      that allows rapid recognition of important relationships. Molecular mechanics is
      able to predict properties (e.g. geometric parameters, conformer stability) of
      several classes of molecules with an accuracy close to the experimental one,
      therefore it plays an important role in complementing molecular graphics. The
      performance of molecular orbital methods increased considerably in the last
      decade thus we can calculate parameters for isolated or interacting molecules
      that are not easily amenable to experiment (e.g. structure and energetics of
      unstable species or activation energies of elementary processes). Computer
      simulation methods provide a link between gas-phase models of microscopic
      structures or processes and macroscopic properties or events that may be derived
      from the former. Thus, it became possible to apply computerised methods for an
      adequate simulation of important events, like chemical and biochemical reactions,
      drug-target interactions, drug delivery and the similar that determine drug
      action. It is stressed that the hardware and software for computer-aided
      molecular modelling may not be absent from the arsenal of a drug designer.

PMID- 9528145
TI  - [Application of protein crystallography in drug design].
AB  - An overview of the application of protein crystallography in drug design is given
      in the paper. First a few basic principles of the systematic target based drug
      design discussed. Secondly are some problems encountered in the process of the
      protein crystallographic analysis are mentioned when it is applied to cases of
      pharmaceutical interest.

PMID- 9528146
TI  - [Structure-based drug design].
AB  - Structure-based drug design is not only a fundamental tool in the search of new
      drugs but also an area of intensive scientific research. The present contribution
      starts with a critical analysis of the potentiality of the structure based design
      and then reviews its methods. Protein crystallography, NMR, homology modelling
      and the use of antibodies are either referenced or briefly described as the
      methods which are able to provide us with the atomic structure of receptors. The
      search of lead molecules by data base mining and by generating structures with
      computers is discussed. Various methods and computer programs for calculating the
      interaction energy between receptors and ligands are reviewed. Several examples
      of successful structure base design are cited and some of them are briefly
      discussed.

PMID- 9528148
TI  - [Computerized logP prediction using fragment methods].
AB  - Lipophilicity, expressed by the logarithm of octanol/water partition coefficient
      (logP) is an important physico-chemical property in rational drug design. Beside
      the experimental determination, the calculation of logP based on the chemical
      structure is frequently necessary. This has led to the development of numerous
      logP prediction methods. In the present paper the fragment type approaches and
      their computer softwares are surveyed (Table I.). The compilation is extended to
      the introduction and evaluation of a recently developed method of Meylan and
      Howard [21]: Atom/Fragment Contribution, AFC method (KOWWIN for Windows,
      software) which possesses the unique option, the Experimental Value Adjusted, EVA
      logP prediction. The author compared the highly precise experimental logP values
      of 28 drugs measured in her laboratory with calculated logP values obtained by
      four approaches: KOWWIN, CLOGP, PROLOGP, ACD/logP. The best prediction was found
      as follows in decreasing order: KOWWIN (r = 0.983), CLOGP (r = 0.978),
      PROLOGP/Combined (r = 0.953), ACD/logP (r = 0.942), PROLOGP/Atomic5 (r = 0.940),
      PROLOGP/Rekker (r = 0.909). The limits of current logP prediction methods
      (intramolecular H-bond formation, tautomerization, conformation changes, etc.)
      and the promising future of the molecular lipophilicity potential, MLP, [42] in
      drug design is also discussed.

PMID- 9528147
TI  - [Three dimensional structure-activity relationships].
AB  - Among the indirect drug design approaches, the 3D QSAR methods have been of great
      importance. They now belong to the most attractive and effective modelling tools
      of modern drug research. In this review, three major topics will be covered. The
      first focuses on the conformational analysis, in the second part the DIstance
      COmparison (DISCO) strategy will be discussed, and in the last part the
      philosophy of the Comparative Molecular Field Analysis (CoMFA) will be briefly
      described and illustrated.

PMID- 9528149
TI  - [Investigation of molecular interactions by chromatographic methods].
AB  - Molecular interactions can be easily determined both by thin-layer and high
      performance liquid chromatography. The theory and practice of the determination
      of molecular interactions and the various methods for the calculation of the
      complex stability is presented. Examples for the application of liquid
      chromatographic methods for the measurements of molecular interactions are
      presented.

PMID- 9528150
TI  - [Editorial. Logo of the Italian Society of Hygiene, Preventive Medicine and
      Public Health].

PMID- 9528151
TI  - [The logo of the Italian Society of Hygiene between Mercury and Aesculapius:
      revisiting history].

PMID- 9528152
TI  - [Survey of air conditioners' characteristics and management in some Italian
      operating theatres].

PMID- 9528153
TI  - [Microbiological environment monitoring (MEM)].

PMID- 9528154
TI  - [Results of an intervention for the improvement of operating room quality and
      safety. Note 1: anesthetic gases].

PMID- 9528155
TI  - [Blood cholesterol levels in 2000 adolescents: results of five years of
      screening].

PMID- 9528156
TI  - [Strategies to increase compliance with elective vaccination: the experience of
      the Health Welfare District of Crema].

PMID- 9528158
TI  - [Kampo therapy for allergic disease].

PMID- 9528157
TI  - [Departmental organization of health care institutions].

PMID- 9528159
TI  - [Therapeutic interventions for allergy updated: antigen-specific approaches].

PMID- 9528160
TI  - [Reevaluation of the roles of leukotrienes in allergic diseases].

PMID- 9528161
TI  - [Investigation of the effects of puff times and spacer devices on the
      distribution pattern of a Becotide 100 inhaler in the twin impinger].
AB  - In order to investigate the dispersion pattern and compare the effect of spacer
      devices (Volumatic, Volumatic Soft and InspirEase), the Becotide 100 inhaler
      actuating 100 micrograms of beclomethasone dipropionate (BDP) per shot was
      studied with respect to its distribution ratio in a twin impinger and also
      compared with that of the Becotide 50 inhaler. The distribution patterns of BDP
      during each stage of the twin impinger were not affected by the puff times of the
      Becotide 100 inhaler. No significant difference was observed when the
      distribution ratios between the Becotide 50 inhaler and Becotide 100 inhaler were
      compared. All of these three spacer devices reduced the deposition ratio in stage
      I which is assumed to be the oral cavity and oropharynx. As the puff times of the
      Becotide 100 inhaler increased, the BDP deposited in the spacer increased and
      that of stage II assumed to be the lung decreased. These results suggested that
      the inhalation volume of BDP would depend on the puff times during clinical use
      and the inhalation volume of BDP for the Becotide 100 inhaler would be double
      that of the Becotide 50 inhaler. The spacer devices could decrease the local
      adverse effects caused by deposited BDP in the oral cavity. When using large
      spacer devices, one or two puff times into the spacer would be recommended for
      the best clinical effectiveness. The Volumatic could be expected to produce a
      superior BDP inhalation volume by reducing the deposition in the oral cavity in
      the 3 spacer devices examined in this study.

PMID- 9528162
TI  - [Buckwheat allergy in 90,000 school children in Yokohama].
AB  - Hypersensitivity to buckwheat allergen frequently causes anaphylactic type
      reactions including urticaria, wheezing, dyspnea and/or shock. Though the
      susceptible pupil would be recommended to be careful for school lunch and picnic
      meals, the prevalence of buckwheat allergy in school children has not yet been
      elucidated. In this study, data on the children allergic to buckwheat were
      collected by sending questionnaire to 341 nurses in elementary school in
      Yokohama. Among the total subjects of this investigation, 92,680 children, the
      incidence of buckwheat allergy was determined 0.22% (140 boys and 54 girls). This
      percentage was not so low level besides the prevalence of such allergic diseases
      as bronchial asthma, atopic dermatitis, allergic rhinitis, allergic
      conjunctivitis and food allergy was 5.6%, 4.2%, 3.1%, 1.6%, and 1.3%,
      respectively. Although a large majority of clinical symptoms of buckwheat allergy
      were urticaria (37.3%), skin itching (33.3%), and wheezing (26.5%). Four children
      (3.9%) experienced anaphylactic shock having a need of medical emergency
      treatment. The incidence of anaphylactic shock due to buckwheat was higher than
      those due to egg and milk allergy. Actually 7 pupil was provoked allergic
      reaction by buckwheat noodle served at school lunch, and 1 pupil at picnic meals.
      Thus, school children allergic to buckwheat is not rare, and it is important to
      withdraw buckwheat food from school lunch and picnic meals.

PMID- 9528163
TI  - [A case of refractory bronchial asthma improving with treatments of sleep apnea
      syndrome].
AB  - A 29-year-old woman of the bronchial asthma was admitted to our hospital. Her
      asthmatic symptoms were refractory in spite of the administration of 30 mg of
      daily-oral prednisolone. During the asthma-attack, marked arterial oxygen
      desaturation was noted. So we doubted that she had obstructive sleep apnea
      complicated with obesity. Sleep Apnea Monitor revealed her nocturnal desaturation
      and frequent sleep apnea. To avoid the desaturation, we recommended her to keep
      prone position during the sleep. And both desaturation and asthmatic symptoms
      were dramatically improved. Nasal-CPAP also had been effective for them. These
      findings suggest that sleep apnea mediated oxygen desaturation may be one of the
      promotor of asthmatic symptoms.

PMID- 9528164
TI  - [Trends of asthma death among adults in Japan 1992-1994. Analysis of 313 cases
      reported questionnaires sent to hospitals with more than 100 beds].
AB  - The Japan Asthma Death Investigation Committee sent questionnaires to hospitals
      with more than 100 beds, and studied the clinical characteristics of 313 reported
      cases who died of asthma between 1992 and 1994. Forty percent of them were at the
      age between 60 and 79. Deaths of young adults in the twenties tended to increase.
      One third of the deaths was due to asphyxia. More than half of the patients were
      classified infectious or mixed type of asthma and 43.9% were graded as severe
      asthma. The main causes of the fatal asthma attacks were respiratory infections,
      fatigue and stress. Insufficient education, low compliance, delay in treatment
      with corticosteroids and other drugs, delay in emergency treatment, past
      histories of life-threatening attacks and hospitalization due to severe attacks
      were suggested to be risk factors of adult asthma death. Pulmonary emphysema
      showed relatively high frequency as a complication.

PMID- 9528165
TI  - [Effects of oxatomide, H1-antagonist, on postinfectious chronic cough; a
      comparison of oxatomide combined with dextromethorphan versus dextromethorphan
      alone].
AB  - H1 antihistamines have been shown to have antitussive effects in patients with
      asthma and postnasal drip. In Japan, no study has been performed to determine
      whether orally administered oxatomide, H1 antihistamine, can reduce the chronic
      cough seen in patients with post-upper-airway infection (postinfection). Patients
      who had chronic cough of more than three weeks' duration and a history of post
      upper-airway infection took part in the study. None had any history of nasal
      disease, gastroesophageal reflux, bronchial asthma, or other chronic pulmonary
      disease. All patients were non-smokers, and none used ACE inhibitors. They had
      normal CRP concentrations, peripheral white blood cell and eosinophil counts,
      serum IgE concentrations, titers of cold agglutinins and antibodies to Mycoplasma
      pneumoniae, chest roentgenograms, and respiratory function tests. A prospective
      randomized, open design was used. The effect of one week of treatment with
      dextromethorphan (D) or with D plus oxatomide (D + O) on the severity of cough,
      as estimated by cough diary, were examined. Twenty-two patients entered the
      study, and 20 were eligible for efficacy and side-effect analyses. Nine patients
      receiving D and 11 receiving D + O completed the protocol. Patients'
      characteristics before the start of the study, such as severity and duration of
      cough, and laboratory data, were not significantly different between the two
      groups. From trial day 5 to 7, improved rates of cough were significantly higher
      with D + O than with D alone (p < 0.05). Combination therapy with oxatomide and
      dextromethorphan reduces subjective perception of cough as estimated by cough
      diary. These results suggest that oxatomide, H1 antihistamine may improve chronic
      cough in patients with post-upper-airway infection.

PMID- 9528166
TI  - [Study on the long-term observation of Nd:YAG laser surgery for allergic
      rhinitis].

PMID- 9528167
TI  - [Evaluation of the effect of short-term application of deep sea water on atopic
      dermatitis].

PMID- 9528168
TI  - Effect of liposome-encapsulated meso-2,3-dimercaptosuccinic acid on mice exposed
      to lead through drinking water.
AB  - Liposomes are the potent carriers of therapeutic drugs for their targeted
      delivery to the intracellular sites specially when the drug is hydrophilic in
      nature and is unable to cross the cell membrane. Lead, a major source of
      environmental pollution, is accumulated in the body system of both animals and
      humans through reticuloendothelial system, the site where liposomes also get
      engulfed upon their entry into the body. In view of these considerations, meso
      2,3 dimercaptosuccinic acid (DMSA), a potent chelating drug used in heavy metals
      intoxication, specially lead, was encapsulated in small unilamellar liposomes
      composed of phosphatidyl-choline and cholesterol (1:1) and used to evaluate its
      efficacy in lead intoxication. DMSA either in free form or encapsulated in
      liposomes was administered intravenously (2,62 mumoles/kg, three injections at a
      gap of 48 hours each, total 7.85 mumoles/kg) to mice which were pre-fed with lead
      in drinking water (500 micrograms/ml) for one month. It was found that only DMSA
      encapsulated in liposomes was significantly effective in reducing the level of
      lead in liver, kidneys and spleen at the dose administered. DMSA either in free
      form or encapsulated in liposomes also restored the inhibition in blood delta
      aminolevulinic acid dehydratase (delta-ALAD) activity. The results suggest that
      liposome encapsulated DMSA may be preferred over free DMSA for reducing the body
      burden of lead.

PMID- 9528169
TI  - Physiological effects of some synthetic food colouring additives on rats.
AB  - Three different synthetic chocolate colourant agents (A, B and C) were
      administered to healthy adult male albino rats for 30 and 60 day periods to
      evaluate their effects on body weight, blood picture, liver and kidney functions,
      blood glucose, serum and liver lipids, liver nucleic acids (DNA and RNA), thyroid
      hormones (T3 and T4) and growth hormone. In addition, histopathological
      examinations of liver, kidney and stomach sections were studied. These parameters
      were also investigated 30 days after colourant stoppage (post effect). Ingestion
      of colourant C (brown HT and indigocarmine) significantly decreased rat body
      weight, serum cholesterol and HDL-cholesterol fraction, while, T4 hormone, liver
      RNA content, liver enzymes (S. GOT, S. GPT and alkaline phosphatase), total
      protein and globulin fractions were significantly elevated. Significant increases
      were observed in serum total lipids, cholesterol, triglycerides, total protein,
      globulin and serum transaminases in rats whose diets were supplemented with
      chocolate colours A and B (sunset yellow, tartrazine, carmoisine and brilliant
      blue in varying concentrations). Haematological investigations demonstrated
      selective neutropenia and lymphocytosis with no significant alterations of total
      white blood cell counts in all rat groups, while haemoglobin concentrations and
      red blood cell counts were significantly decreased in the rats who were
      administered food additives A and B. Eosinophilia was noted in rats fed on
      colourant A only. No changes were recorded for blood glucose, growth hormone and
      kidney function tests. Histopathological studies showed brown pigment deposition
      in the portal tracts and Van Kupffer cells of the liver as well as in the
      interstitial tissue and renal tubular cells of the kidney mainly induced by
      colourant A. Congested blood vessels and areas of haemorrhage in both liver and
      renal sections were revealed in those rats who were given colourants B and C.
      There were no-untoward-effects recorded in the stomach tissue.

PMID- 9528170
TI  - [Formulation and stability of suspensions for preclinical study].
AB  - In preclinical studies, poorly soluble drugs are usually administered orally to
      experimental animals as suspensions. The present study was aimed at providing
      data allowing predictive estimations of the stability of such suspensions. To
      this purpose aqueous suspensions of three drugs (griseofulvin, ibuprofen and
      indomethacin) were prepared at different concentrations using four different
      suspending agents: sodium carboxymethylcellulose (CMC), microcrystalline
      cellulose/carboxymethylcellulose (MC/CMC), hydroxypropylmethylcellulose (HPMC)
      and jota carragenaan (CJ). The physical and physico-chemical characteristics of
      the drugs, the rheological properties of the suspending media and of the
      corresponding drug suspensions, and the physical and chemical stability of the
      suspensions was then evaluated. The type of suspending agent, rather than the
      physical characteristics of the drug, appeared to exert the main influence on the
      physical stability of suspensions. The most stable formulations were produced by
      suspending agents with low-temperature gelation characteristics (CJ) or with
      thixotropic flux (MC/CMC).

PMID- 9528171
TI  - [Eboritic preparations for topical use].

PMID- 9528172
TI  - Effect of various marine lipids on transdermal drug delivery--in vitro
      evaluation.
AB  - The effects of several marine lipids on the penetration of hydrocortisone and
      nitroglycerin through excised hairless mouse skin have been studied. Fatty acid
      extracts obtained by hydrolysis of Portuguese dog-fish-liver-oil or by hydrolysis
      of cod-liver-oil were shown to be effective skin penetration enhancers.
      Phospholipid obtained from squid was also shown to be effective enhancer.
      However, the enhancing effect of the marine products could generally be
      associated with their content of free unsaturated fatty acids. The fatty acid
      extract obtained from cod-liver-oil caused insignificant skin irritation when
      incorporated into an ointment base and applied to human skin.

PMID- 9528173
TI  - Use of dika fat in the formulation of sustained release frusemide encapsulated
      granules.
AB  - Sustained release frusemide granules were formulated with Dika fat, a vegetable
      oil extracted from the kernels of Irvingia gabonesis Var excelcia. Granules
      containing 60% w/w, of Dika fat and 200% w/w frusemide and lactose were prepared
      using the fusion method. Prepared granules (passed through 0.600 micron stainless
      steel sieve) were encapsulated such that each capsule contained frusemide
      granules equivalent to 75mg of the pure drug. Granules of same size fraction
      containing 10% w/w maize starch, or alginic acid and 60, 20, and 10% w/w of Dika
      fat, frusemide and lactose respectively were similarly prepared and encapsulated.
      Dissolution profiles of the encapsulated granules were assessed in 0.1 sodium
      hydroxide, simulated gastric fluid (SGF) and simulated intestinal fluid (SIF)
      without enzymes. Results obtained indicated sustained release of frusemide in the
      presence of Dika fat. The presence of maize starch modulated the release of
      frusemide while the presence of alginic acid could not show significant (P <
      0.05) enhancement on frusemide release. Dissolution of frusemide was greatest in
      0.1N NaOH and least in SGF. Drug release from the matrices was of mixed order
      with diffusion controlled mechanism and leaching process occurring together to a
      greater extent.

PMID- 9528174
TI  - Myocardial fatty acid pattern in rats fed on an erucic acid enriched diet.
AB  - Individual lipid classes and their fatty acid pattern in myocardium of rats fed
      on a diet containing 10% erucic acid ethyl ester (cis-13-docosenoic acid ethyl
      ester) were investigated and compared to rats fed on a normal diet. Two groups of
      rats were treated for 10 consecutive days with the erucic acid ethyl ester diet
      and the standard diet, respectively. After extracting total lipids from the
      myocardium of the rats, the individual lipid classes and the percentage of fatty
      acids in phospholipids, free fatty acids, diglycerides and triglycerides were
      measured. The data obtained demonstrate that the erucic acid ethyl ester diet
      induces a marked increase in free fatty acids and in triglycerides and marked
      differences in fatty acid pattern in triglycerides, free fatty acids and
      diglycerides, but only marginal differences in phospholipids, which seem to be
      carefully preserved as fundamental components of cell and mitochondria membranes.

PMID- 9528175
TI  - [Hundredth birthday of Professor Henri Baruk].

PMID- 9528176
TI  - [A new Military Medical Service for the 21st century: a necessity].
AB  - The Military Medical Service is at the cross-road of two deep restructurings,
      that of Defense and that of the public health system. It will have to be capable
      of supporting a professional army prepared to conduct foreign operations. The new
      Military Medical Service relies on seven basic principles which have been
      submitted to the National Academy of Medicine for examination. It will obviously
      have to face many challenges.

PMID- 9528177
TI  - [Personnel with poor vision at fighter pilot school].
AB  - The piloting of fighting aircraft, the navigation of space-shuttle, the piloting
      of an helicopter in tactical flight at an altitude of 50 metres require the use
      of all sensorial, ocular, vestibular, proprioceptive ... sensors. So, the
      selection and the follow-up of these aerial engines' pilots need a very complete
      study of medical parameters, in particular sensorial and notably visual system.
      The doctors and the expert researchers in Aeronautical and spatial Medicine of
      the Army Health Department, which have in charge the medical supervision of
      flight crew, should study, create, and improve tests of visual sensorial
      exploration developed from fundamental and applied research. These authenticated
      tests with military pilots were applied in ophthalmology for the estimation of
      normal and deficient vision. A proposition to change norms of World Health
      Organisation applied to the vision has been following these to low visual persons
      was equally introduced.

PMID- 9528178
TI  - [Objectives, results and future prospects of burn treatment in 1997].
AB  - When burn injuries to the skin are extensive, delays in wound closure contribute
      to multiple organ failure because the availability of donor sites does not allow
      early and permanent coverage of excised wounds. From 1991 to 1996, 30 patients
      with a mean burn size of 78% total body surface area (65% full-thickness)
      underwent skin grafting with autologous cultured epidermis (AEC) performed in the
      labs of Genzyme Tissue Repair Company. Twenty three were adults and seven
      children under 15 (mean age 29, range 2.5 to 70); 27 suffered inhalation injury;
      3 presented with multiple trauma and 2 with blast injury. As soon as possible
      wound beds were excised and temporarily covered with allografts or with sandwich
      or meshed autografts; the mean surface covered with autografts was 28 +/- 12%.
      Keratinocytes grafts were applied to a mean of 37 +/- 16.5%, an average of 210
      grafts of 25 to 30 cm2. Three patients died respectively at day 67, 81 and 90. At
      time of gaze backing removal, the mean percentage of culture engraftment was 69%
      (range 25 to 95); this engraftment was higher for children (74%) and very bad
      above 60 (25%). The mean length of hospitalisation was 114 +/- 30 days. The
      definitive coverage by AEC was evaluated through the percentage of secondary
      autografted area: 10 +/- 9.5% (range 0 to 46). The average cost by patient was
      98,500$ or 16$ by cm2 of culture. The weakness of epithelialisation makes
      essential a dermal support to the keratinocytes cultures, allodermis is now
      currently used, perhaps the new skin substitutes will give the ideal missing
      piece.

PMID- 9528179
TI  - [Epidemiologic surveillance in the Army and Public Health: as exemplified by
      rubella].
AB  - Since 1993, several outbreaks of rubella are annually reported from the French
      military. This trend reveals a transfer of the reservoir of wild virus towards a
      non-immune population of male adolescents and young adults, as a result of the
      rubella control programmes. This paradoxical phenomenon should disappear within
      the next decade, when the new vaccinal schedule including a combined measles,
      mumps and rubella vaccine for the children of both sexes 11 to 13 years old will
      have been implemented. Meanwhile, the military system of weekly epidemiological
      report will be usable as a national observatory for the rubella. Moreover,
      providing specific data in real time, it will be able to support a strategy of
      intervention for an early neutralization of epidemics.

PMID- 9528180
TI  - [Combat psychiatry or psychiatrist on the battlefield?].
AB  - Military psychiatrists, close to the troops, during the external operations in
      which the French army is involved since some years, are reviving with an
      operational battlefield practice. What they owes to their predecessors is
      actually included in a discipline, a military institution, and a society which
      have evolved. Psychosocial psychiatric practicing, in such an opportunity, finds
      a privileged source of reflections and lessons. Some of them may be used beyond
      their initial specific frame.

PMID- 9528181
TI  - [Epidemiology of cervical and endometrial cancer].
AB  - In 1995, in France, the estimation of the cervix cancer incidence, with 3,300 new
      cases, is of 10.3 per 100,000, and the incidence of the endometrial cancer with
      3,268 new cases, is of 13.8 per 100,000. The decrease of the incidence of the
      cervical cancer is of more than 50%, in 1975, the incidence was of 22.4 per
      100,000. For the endometrial cancer, the decrease is insignificant, as in 1975,
      the incidence was of 14.4 per 100,000. This phenomenon has been observed in most
      european countries. The incidence of the adenocarcinoma of the cervix remains
      stable. The relative survival at 5 years, at all ages in the French cancer
      registry of Bas-Rhin is of 65% for the cervical cancer and of 73% for the corpus
      uteri cancer. However, no improvement has been observed since 1975. The risk
      factors are quite well-known concerning the cervical cancer, there is a strong
      correlation with the sexual activities, age at first intercourse, the
      multiplicity of the partners, which clearly shows that the cervical cancer is a
      sexually transmitted disease. Concerning the endometrial cancer, the risk factors
      are mostly linked with the reproductive life: age at menarche, parity, age at
      first birth, menstrual irregularities, infertility and menopause.

PMID- 9528182
TI  - [Human papillomaviruses and carcinogenesis of the uterine cervix: future
      prospects in the domain of detection and prevention].
AB  - It is now admitted that certain genotypes of human papillomavirus (HPV), mainly
      HPV types 16 and 18, play an etiological role in the origin of the great majority
      of invasive carcinomas of the uterine cervix and their intraepithelial
      precursors. Such an evidence has modified our understanding of the natural
      history of cervical cancer and should result in new approaches for the early
      diagnosis and prevention of precursor lesions. Sensitive, specific and reliable
      HPV detection tests have been progressively designed but their use as routine
      tests requires multicentric studies, involving large series of women, to evaluate
      their usefulness in the clinical management or the screening of patients and to
      establish their limits and cost-effectiveness. It is already most likely that the
      association of HPV detection tests to cervicovaginal cytology would increase the
      detection rate of high-grade intraepithelial neoplasia and constitute a means for
      quality control in cytology. The viral origin of most cancers of the uterine
      cervix paves the way for their prevention by vaccination against the main
      oncogenic HPV genotypes and provides hope for specific immunotherapy of
      associated neoplasia.

PMID- 9528183
TI  - [Precancerous states of the endometrium: hormonal aspects].
AB  - The two types of endometrial carcinomas are preceded by precancerous lesions.
      Type I endometrial carcinomas are most commonly encountered in perimenopausal
      women with the classical risk factors associated with estrogen exposure: obesity,
      multiparity, diabetes, estrogen treatment, ... Hyperplasia (simple, followed by
      complex forms without cellular atypias and subsequently by complex hyperplasias
      with cellular transformation) precede such cancers. Estrogens exert a promoting
      effect on these lesions but do not initiate them. Progesterone and progestins
      exert a preventive and protective effect. However, the progressive loss of
      steroidal receptors is correlated to the progression of tissular anomalies and to
      the onset of cytogenetic anomalies and to mutations of p53 anti-oncogene. The
      preventive role of progestin is well established, but their curative beneficial
      effect on atypical precursors forms of endometrial cancers and on endometrial
      carcinomas remains controversial. The second type of endometrial cancer appears
      during the postmenopause and is characterized by an increased invasiveness and a
      poor prognosis, devoid of identifiable risks factors, these aggressive cancers
      are not preceded by hormone-sensitive precancerous lesions, but by an intra
      epithelial endometrial carcinoma. This lesion appears most often in an atrophic
      endometrium. Finally, the two types of precancerous states are characterized by
      distinct gene anomalies suggesting two different pathogenic mechanisms of
      cancerisation.

PMID- 9528184
TI  - [Screening of cervical cancer, an action of public health, a problem of society].
AB  - Well organized, the cervical cancer screening is very efficient and theoretically
      allows a decrease of the cumulative incidence of 93.5% if smears are taken each
      year, and 90.8% if it is taken every three years. However, this screening is
      regularly controversed concerning the age of the target population and the
      frequency of the smear. It is important that the health authorities are aware
      that the screening can only be justified if well managed, well evaluated, and
      endowed with a quality insurance system. In France, the conditions of an
      efficient screening are not gathered. The practitioners should have a minimum
      education in public health in order to be able to understand well that screening
      does not obey the same ethical, deontological rules and organization that the
      curative medicine. Imposing a high frequency of the smear has deleterious effects
      on women and is responsible of a bad use of the resources.

PMID- 9528185
TI  - [Non-surgical prevention of uterine cancer].
AB  - Non surgical prevention of uterine cervical cancer relies on regular performance
      of Pap smears and colposcopy. Screening for cervical dysplasia allows their
      treatment by laser vaporisation or cone biopsy, according to their grade, and
      therefore the prevention of invasive carcinoma. Unfortunately, 40% of the female
      population does not comply to cervical screening and Pap smears entail 20% false
      negative results. Prevention of endometrial carcinoma is even far more difficult
      in that endometrial smears are seldom practised. Periodic surveillance of women
      receiving oestrogenic hormonal therapy, addition of progesterone in order to
      eventually protect the endometrium, hysteroscopic detection of irregular
      endometrial hyperplasia, represent the only tools available today.

PMID- 9528186
TI  - [Prevention of cervical and endometrial cancer: role of surgery].
AB  - Epidemiology and natural history of cervical and endometrial carcinomas are not
      identical. So, the part of surgery in their prevention is different. For cervical
      carcinoma, mass screening and prevention allowed reduction of rates of incidence
      and mortality. Surgery concerns such intra-epithelial neoplasias. All the
      procedures, either destructive, either ablative, expose to failures as recurrence
      of intra-epithelial neoplasia and more as invasive carcinoma. For high grade
      epidermoid intra-epithelial neoplasia, conisation is the best of ablative
      procedures to set up an accurate pathologic diagnosis and consequently to
      determine adequate therapy: conservative by conisation, total hysterectomy or
      extended hysterectomy and lymphadenectomy. For in situ adenocarcinoma, removal of
      the whole cervix or total hysterectomy appears in numerous circumstances more
      safety. For endometrial carcinoma, there is no efficacious screening nor
      secondary prevention procedure available. Natural history, specially pre-invasive
      disease, is not well known. Atypical hyperplasia is a real pre-invasive disease
      and evolve to invasive carcinoma in 25%, and no more than 25% of this lesions
      regress under progestative therapy. Destructive procedures, biopsy-curettage and
      even endometrectomy under hysteroscopy don't realise and efficacious treatment of
      atypical hyperplasia and prevention of carcinoma. Total hysterectomy is the only
      one true prevention of endometrial carcinoma after failure of progestative
      therapy for patients who desire be pregnant, in first place for women who don't.

PMID- 9528187
TI  - [Experimental and human nephrotoxicity induced by ochratoxins].
AB  - Ochratoxin A is a mycotoxin: a dihydroisocoumarin derivative linked to L. beta
      phenylalanine. Ochratoxin A is produced by a number of Aspergillus and
      Penicillium species. This mycotoxin is a carcinogenic, teratogenic, mutagenic and
      immunosuppressive substance. Ochratoxin A is a common contaminant found in a
      variety of foods for human nutrition as well as animal feeds. The aim of this
      study is to discuss nephrotoxic properties of this mycotoxin in humans.
      Nephrotoxicity has been reported in many animals after exposure to ochratoxin A.
      Porcine nephropathy due to this mycotoxin is a well known disease characterized
      by impairment of proximal renal function. Renal damage is also confined to the
      proximal tubule in other animal species. A good correlation is found between
      renal function abnormalities and the location of the lesions along the nephron.
      Of particular interest is the presence of nuclear abnormalities of the epithelial
      cells with pyknosis, karyorrhexis and karyomegaly. The question is to know if
      ochratoxin is nephrotoxic in humans. Acute nephrotoxicity seems to be very rare
      and we found only one case report suggesting such a possibility. We observed the
      occurrence of chronic renal failure in two patients with a possible
      responsibility of a chronic ochratoxin A intoxication. Clinical and histologic
      findings in these two patients were quite similar to those described in several
      cases of karyomegalic interstitial nephritis. Striking similarities between the
      changes in renal structure and function seen in ochratoxin A-induced experimental
      nephropathies and in Balkan endemic nephropathy suggest a common etiologic agent.
      This mycotoxin could be also responsible for interstitial nephropathies in North
      Africa.

PMID- 9528188
TI  - [Analysis of expression of the molecules Igalpha and Igbeta in human pro-B
      leukemic lines].
AB  - Ig alpha and Ig beta are two glycosylated transmembrane proteins of the Ig
      superfamily that are encoded by the B cell-specific genes mb-1 and B29,
      respectively. Ig alpha/Ig beta heterodimers may associate with the mu/surrogate
      light chains (psi LC) complex and with membrane Immunoglobulins on the surface of
      pre-B and B cells, respectively. They play a crucial role in the signal
      transduction that follows pre-B and B cell receptor cross-linking. Previous works
      have shown that mb-1 and B29 transcripts are expressed in normal mouse and human
      pro-B cells. However, little is known about the expression of Ig alpha and Ig
      beta molecules in pro-B cells. To address this issue we first analysed the
      expression of the Ig alpha and Ig beta molecules in the RS4; 11 and Nalm16 human
      pro-B cell lines using specific monoclonal antibodies. We found that both cell
      lines expressed Ig alpha and Ig beta but this expression was limited to the
      cytoplasm compartment. Three forms (44, 40 and 36 kDa) of the Ig alpha molecule
      and a single form (36 kDa) of the Ig beta molecule were detected in these lines.
      The heterogeneity of the Ig alpha molecule was partly related to the presence of
      a truncated Ig alpha protein which is likely the product of a short mb-1
      transcript expressed in these cell lines. This short transcript is generated by
      alternative splicing of the mb1 mRNA with loss of exon 2. Ig alpha heterogeneity
      was also related to the expression of different glycosylated forms of the Ig
      alpha molecule. Only a minor fraction of the Ig alpha and Ig beta molecules
      associate with each other to form Ig alpha/Ig beta heterodimers and Ig beta
      homodimers. In these pro-B cell lines Ig alpha and Ig beta were found to
      associate with the lyn tyrosine kinase, suggesting that they may play some
      functional role at this B cell differentiation stage. Transfection of muHC gene
      in the Nalm16 cells results in the assembly of the pre-B receptor and in its
      expression on the cell surface. The level of surface expression of the pre-B
      receptor was found to correlate with the level of muHC and psi LC synthesis and
      with the level of association of the different components of the pre-B receptor
      with each other. Analysis of the 697 and Nalm6 pre-B cells and of the Ramos B
      cells indicated that heterogeneity of Ig alpha and Ig beta increases as a
      function of B cell differentiation.

PMID- 9528189
TI  - [Ethics, bioethics and medical sciences].
AB  - The aim of bioethics is to define a wise conduct for humans with regard to their
      environments, whether living or inanimate. However, owing to their diversity,
      bioethics can only deal with general problems such as biodiversity. Within the
      framework of bioethics as a whole, different sectorial bioethics must therefore
      exist to deal with problems specific to certain environments, for example the
      Oceans and Seas, the Forests. General bioethics and sectorial bioethics have an
      important contribution to make to medical sciences but official regulations
      should be proposed only after an attentive investigation has been made. For
      instance, the preservation of an apparently threatened biodiversity or the
      revival of a seriously damaged biodiversity must be the subject of a thorough
      preliminary scientific study and, if legislative decisions are taken, a very
      careful scientific control of their consequences must be carried out. One example
      is given: the decree on the protection of Larids and its impact, with regard to
      an abusive proliferation of certain gull populations having varied effects on
      public health. Sectorial bioethics can also have obvious consequences on medical
      sciences. Thus various harmful attacks on coral reefs (contrary to the concepts
      of thalassoethics) can lead to the death of corals and the appearance of
      ciguatera. Thalassoethics, by inciting pollution control, should help to improve
      the conditions of thalassotherapy. Forest ethics, particularly concerning
      management, can reduce the greenhouse effect and its consequences on health, as
      well as protecting plant and animal species inhabiting the ecosystem and bringing
      new chemical bodies to inspire original pharmacological research. Thus the links
      between general or sectorial bioethics and medical sciences must always be very
      close.

PMID- 9528190
TI  - [The protein of fibrocystic breast disease--methods of measurement and clinical
      implications].
AB  - The gross cystic disease of the breast has been reported to be associated with a
      two to fourfold increased breast cancer risk. The cyst fluid contains several
      hormones and proteins among whom we have isolated and characterized one of these
      proteins with an estimated molecular weight at 17.4 kilodaltons (Gross Cystic
      Disease Fluid Protein-17 kDa or GCDFP-17). A specific antiserum against GCDFP-17
      was produced and an enzyme-linked immunosorbent assay (ELISA) was perfected to
      obtain a simple and sensitive method for the study of the GCDFP-17. This protein
      is also stimulated by androgens in vitro like in vivo and is a potential marker
      of an androgens' excess. Subsequently, we were able to study 33 ovarian
      micropolycystic syndromes (OPCS) with a biological hyperandrogenism
      (Hyperandrogenic Group or GH) compared with 32 control women (GT). The body mass
      index (BMI) of GH was significantly greater than that of G.T. (29.8 +/- 9.3 vs
      21.3 +/- 2.7 kgs/m2--p. < 0.01). The mean plasma value of testosterone (T), delta
      4-androstenedione (delta 4-A), dehydroepiandrosterone sulfate (SHDA) and the
      ratio of T. on sex binding protein (SBP) or free testosterone index (ITL) were
      significantly greater in GH than in GT (p < 0.01). Despite the circulating excess
      of androgens in GH, there were no significant differences for GCDFP-17 between
      the 2 groups (G.H. = 222 +/- 74 vs G.T. = 230 +/- 84 ng/ml) and any correlation
      between plasma androgens and GCDFP-17 (p < 0.05). Nevertheless, the androgens'
      excess in G.H. was clearly smaller than that which was seen with the doses of
      potent androgens used in the treatment of metastatic breast cancer.

PMID- 9528191
TI  - [The nursing training course during the first stage of medical studies].

PMID- 9528192
TI  - [Use of pediculicides].

PMID- 9528193
TI  - [Presence of HLA-DRB1 alleles in a group of patients with rheumatoid arthritis
      treated with low doses of sodium aurothiomalate].
AB  - The good results of a therapy with small doses of sodium aurothiomalate (20
      mg/month) in 17 patients suffering from rheumatoid arthritis are reported. The
      mean age +/- ESM at the beginning of treatment was 59.9 +/- 3.2 years, the mean
      duration of disease was 1.3 +/- 0.5 years. The lowest grade of disease activity
      (1) according to Mallya and Mace's (1981) criteria was observed in 12 patients
      (70%) after a period of 1.7 +/- 0.6 years (mean +/- ESM). This grade of activity
      persisted in 11 patients and remained for 3 years in 1 patient. In the other 5
      patients a low or middle activity of disease persisted. The relationship between
      therapeutic results and HLA DRB1 prevalence was investigated. The LLEQRRAA and
      LLEQKRAA sequences are present in 3 patients, i.e. 17.9%. This frequency is not
      significantly different from the frequency (28.6%) observed in a control group of
      healthy subjects. Therefore these sequences, at least in Italian people, cannot
      be considered a factor of susceptibility to RA. They may be a factor of evolution
      to a more severe disease. Dermatological side effects were evident only in 2
      patients; one of these patients was HLA DR5 positive. The results observed in DR7
      positive patients were not different from the results observed in the other
      patients; therefore, DR7 positive patients could responders to gold treatment,
      even with low doses.

PMID- 9528194
TI  - [Epidemiology and clinical framework of the ischemic pathology of the lower
      limbs].
AB  - The atherosclerotic disease is a very important problem for the health in the
      advanced countries. The Rose's questionnaire was utilised for diagnosing the
      intermittent claudication but the current diagnostic method is the ankle-arm
      blood pressure ratio (Winsor's index). The incidence of intermittent claudication
      is 0.4% to 14.4%, utilising the Rose's questionnaire and 4.2% to 35% using the
      Winsor's index. The main risk factor for the peripheral arteriopathies is the
      smoke followed by the hypertension and the diabetic disease. The dyslipidemic and
      coagulative diseases are important risk factors in some populations. The main
      cause of death is the myocardial infarction. The risk increases when it is
      present a cerebral or coronary arterial pathologies.

PMID- 9528195
TI  - Acute effects of octreotide, cabergoline and a combination of both drugs on GH
      secretion in acromegalic patients.
AB  - PURPOSE: The acute GH lowering effects of a single dose of either octreotide
      (OCT) or cabergoline (CAB), given alone and in combination, were studied in a
      series of 21 patients with acromegaly. PATIENTS AND METHODS: Plasma GH was
      measured for 8 hours after a single subcutaneous injection of OCT (100
      micrograms) and for 48 hours after a single oral dose of CAB (0.5 mg) in all
      patients. Fourteen patients, who did not suppress GH levels below 5 micrograms/L
      after either OCT or CAB given alone, also received a combination of both drugs
      (OCT 100 micrograms s.c. + CAB 0.5 mg p.o. 24 h before OCT). RESULTS: GH levels
      were acutely suppressed by more than 50% in 15/21 cases after OCT alone and in
      5/21 after CAB alone, respectively (P < 0.01). In the 14 patients who received
      the combined test, the magnitude of GH suppression was significantly higher than
      after OCT alone 4, 6 and 8 hours after OCT administration (P < 0.02). In patients
      with mixed GH/PRL-secreting tumors, the additive effect of OCT and CAB was
      observed at each time point. CONCLUSION: These results suggest that combined
      therapy with OCT and CAB may be more effective in suppressing GH secretion than
      either compound given alone, especially in patients with GH/PRL-secreting
      adenomas.

PMID- 9528196
TI  - [Effects of subacute treatment with S. Croce water from the Sponga Springs in a
      group of dyspeptic patients].
AB  - The Authors have appraised, in a group of 20 patients suffering from "non-ulcer,
      non-reflux dyspepsia", the therapeutical action and tolerance of the oligomineral
      Santa Croce water from the Sponga spring administered at a dose of 500 mL with
      the main meals up to an overall quantity of 1.5 L per day for ten days. When
      compared with a comparable control group, taking fairly mineralized water of
      known composition and free of contaminants, the group of patients treated showed
      a significant reduction both in the number and intensity of the symptoms marking
      the dyspeptic condition including above all pyrosis and sensation of epigastric
      heaviness and laborious digestion. As a first hypothesis, the hydropinic
      treatment might have indirectly favoured post-prandial gastric emptying, through
      an action of reduction of endogastric osmolarity and pH. The only collateral
      effect, reported by only five subjects, consisted of an annoying pollakiuria and
      nycturia.

PMID- 9528197
TI  - [Effects of the triple therapy in the eradication of Helicobacter pylori:
      comparison of 3 different antibiotics].
AB  - To compare the effectiveness, in eradicating Helicobacter pylori infection, of
      three different antibiotics in combination with omeprazole and metronidazole, in
      order to establish which might be best in clinical practice. One hundred twenty
      three patients with HP-positivity, assessed by CLO-test and histology were
      studied. They were randomly assigned to the following therapies: clarithromycin
      (500 mg thrice daily) for 14 days, amoxycillin (twice daily) for 14 days,
      azithromycin (500 mg once daily) for 6 days, in combination with omeprazole
      (twice daily for 20 days and once for one month plus metronidazole (500 mg twice
      days) for 10 days. The eradication rate, among the three groups, was 97%, 80% and
      68% respectively (p = 0.009); no statistical differences were remarked also
      between the group treated with amoxicyllin and that with clarithromycin, and
      between the group treated with amoxicyllin and that with azithromycin; there was
      only a statistical difference between the group treated with azithromycin and
      that with clarithromycin (p = 0.005). The Authors suggest that all the three
      antibiotics are effective in curing Helicobacter pylori infection and, that, the
      various use of the three antimicrobials should be evaluated from time to time on
      the basis of clinical data of the patients.

PMID- 9528198
TI  - [Peridural analgesic therapy in orthopedic surgery: comparison of ropivacaine and
      bupivacaine].
AB  - The aim of our study was to compare the efficiency of ropivacaine and
      bupivacaine, in epidural administration, in postoperative analgesia. 20 patients,
      undergone knee surgery, in epidural anaesthesia (bupivacaine 0.5%-2 mg/Kg-1
      administered in level L3L4), was divided into 2 groups (10 each one) and the
      local anaesthetics in study was administered by epidural catheter with an
      elastomeric pump: A (ropivacaine 0.15%) and B (bupivacaine 0.15%). The results
      demonstrate that ropivacaine is better than bupivacaine to keep a check on
      analgesia in postoperative pain.

PMID- 9528199
TI  - [Clinical tolerance of oral loading with elevated doses of amiodarone in a group
      of patients with heart failure].
AB  - Amiodarone is a choice drug for the treatment of patients suffering from life
      threatening hyperkinetic ventricular arrhythmias and depressed ventricular
      function. The drug is characterized by a remarkably long halflife and a delayed
      initial activity after oral administration of the usual loading levels. The aim
      of this study was to establish: -the clinical tolerance to elevated doses in
      patients with heart failure presenting complex, hyperkinetic ventricular
      arrhythmias; -the possibility to shorten hospitalization as a result of the oral
      loading; -whether this administration route would take less time to be
      efficacious. For this purpose, 30 patients with heart failure and complex,
      hyperkinetic ventricular arrhythmias were treated with 0.50 mg/kg body weight of
      amiodarone for three days and with 0.30 mg/kg on the 4th and 5th days, followed
      by a maintenance period of treatment with 200-400 mg daily. All patients
      underwent a 24-h Holter test before and after administration and an
      echocardiographic examination showing an average ejection fraction of
      approximately 30%. Amiodarone was clinically well tolerated; only 2 patients
      required discontinuation of therapy whereas, among the the remaining 28 patients,
      2 cases of transient hypotension and 3 cases of gastroenteric disorders were
      observed. It was concluded that elevated doses of amiodarone were well tolerated,
      which allowed to reduce the loading period and, therefore, hospitalization.

PMID- 9528200
TI  - [Use of mivacurium in orthopedic surgery: comparison of 2 different-dose
      inductions].
AB  - The aim of our study was to evaluate the efficiency and safety of mivacurium,
      comparing two dose-induction in patients undergone a minor orthopaedic surgery.
      30 patients were divided into two groups and mivacurium were administered at the
      dose of 0.15 mg Kg-1 and 0.20 mg Kg-1 respectively. The results confirmed its
      efficiency in short surgery. Mioresolution was excellent only in the second group
      (0.20 mg Kg-1) despite an histamine-related blood pressure reduction.

PMID- 9528201
TI  - [Observations on organic components of thermal mud: morphohistochemical and
      biochemical studies on lipid components of mud of the Terme dei Papi (Laghetto
      del Bagnaccio, Viterbo). Chemical bases of the interpretation of biological and
      therapeutic actions of thermal mud].
AB  - In previous findings the lipidic fractions extracted acc. to Folch from the
      mature muds of the majority of the Italian thermal springs hot baths was studied,
      with the aim to identify the organic substrates of their therapeutical activity.
      The organic components of the "mature" peloids are produced by the metabolism of
      the microphytozooplankton growing spontaneously in the clay-substrate, in contact
      with the hot water. The Popes thermal springs (Bagnaccio's Lake) are
      characterised by an unique environmental situation, because the muds are
      naturally matured in the hot thermal water, but not in artificial baths. The
      morphohistochemical aspects of thermal algae growing in the Bagnaccio's lake have
      been studied by means of Computerised Optic Probe Video-Microscopy, using a not
      contact zoom objective 70-400x. Peloid types, both the "white" and the "black"
      contains yellow pigments, fragments of hyphae, monocellular algae, Diatomeae,
      Cyanophyceae and few other species. The biochemical aspects of the muds extracts
      are characterised by the presence of Phospholipids (PC, PE, PS, SP), a series of
      Hydrocarbons ranging from C30 to C38, Phytosterols (beta-sitosterol, Campesterol,
      Stigmasterol and traces of Cholesterol), Free Fatty Acids (Palmitic, Palmitoleic,
      Myristic, Stearic, Oleic and Linoleic, heptadecenoic and heptadecanoic) and
      Terpenes (beta-amirrhyne, 24-methylene-cyclo-arthanole). In our opinion, the
      therapeutic effects of the mature muds are related to its organic components,
      with special regards to Phospholipids, Phytosterols and Terpenes. The richness of
      these components in the Popes Thermal springs seems to be great interest in the
      dermatological and cosmetic applications, other then the traditional use.

PMID- 9528202
TI  - [Malaria: recent immunological acquisitions and therapeutic prospects].
AB  - Malaria remains one of the major health problems in many tropical countries. The
      asymptomatic carrier status is common and about 100% of the children in highly
      endemic areas have Plasmodium falciparum parasitaemia at any given time.
      Consequently a case definition based on the mere presence of parasites in the
      blood is non-informative in terms of measuring morbidity. Acquired clinical and
      parasitological immunity develop progressively over several years after repeated
      exposure to infection. Protection is acquired first again death or severe
      clinical disease, but protection against infection is never complete, moreover it
      is still not known why some infections are mild an some fatal. Although virulence
      markers on the parasite have not been identified with certainty, there are some
      indications that parasites differ in virulence. The genetic composition of human
      many also play a role in the defence against the parasite, so the immune
      mechanisms responsible for the acquired immunity remain uncertain. In fact, an
      infection by Plasmodium falciparum induces a variety of immune responses,
      including humoral and cellular, which can be specific or non-specific responses,
      some of which are protective, but against which the parasite has evolved
      effective escape measures. Vaccines has proven a most effective measure to
      control infectious diseases, but no consistently effective vaccine has yet
      developed against a human parasitic disease. A malaria vaccine aimed at
      disrupting the parasites life cycle at one or more of the three stages
      (sporozoite or pre-erythrocytic stage, asexual blood or erythrocytic stage, and
      sexual or sporogonic stage) might be a long-term solution.

PMID- 9528203
TI  - [Review on renal calculosis in pregnancy].
AB  - By the analysis of the series reported by many authors, urolithiasis in pregnancy
      seems to be a rare, but significant pathology. The disease, potentially dramatic
      for the mother and fetus, appearing into a such particular physiological state
      like is pregnancy, suggests a reevaluation of diagnostic and therapeutic methods
      and better control of maternal and fetal risk. Furthermore, urolithiasis must be
      considered as cause of premature birth, a very severe complication of pregnancy
      the incidence and predisposing factors of urinary tract stones are generally the
      same in nonpregnant women. But any metabolic effects and the anatomical changes
      happen in pregnancy can have a important role on stone's formation. Signs and
      symptoms in urinary stone disease are: colic, flank pain, hematuria, urinary
      tract infection; irritative voiding, fever. The initial evaluation and treatment
      are again similar to those used for the non pregnant population. Radiographic
      studies any way must be used with caution for the risks of the ionizing
      radiations for the fetus. All forms of treatment with the exception of
      extracorporeal shock ware lithotripsy, are appropriate in the pregnant patients
      but naturally very useful, for the appropriate care of these patients is the
      coordination by the urologist, the obstetrician, the pediatrician, the
      radiologist and the anesthesiologist.

PMID- 9528205
TI  - [Alterations of hemostasis in liver cirrhosis of the dog].
AB  - In seven dogs with histologically proven liver cirrhosis the activity of the
      single coagulation factors with the exception of factor VIII:C, of the inhibitors
      antithrombin III and protein C as well as plasminogen and alpha 2-antiplasmin was
      distinctly lower than in the control group (p < 0.0001). The changes of the
      factors VII [median (x0.50) = 17 %] and X (x0.50 = 18 %) as well as of protein C
      (x0.50 = 15 %) were particularly pronounced. Diminution of activity certainly
      exceeded also in nearly all of the remaining haemostatic proteins the decrease of
      albumin concentration. Besides the shorter half life time, this reflected an
      increased consumption in consequence of intravascular coagulations and
      fibrinolysis. The latter could also be seen from the significantly increased
      concentrations of soluble fibrin and fibrin(ogen) degradation products.
      Therefore, the alterations of the haemostatic system measured in dogs in many
      details were in accordance with findings in human beings suffering from liver
      cirrhosis.

PMID- 9528206
TI  - [Effect of energy level of rations and time of blood sampling on the relative
      activity lf LDH isoenzymes in the serum of lambs].
AB  - The effect of the energy level of the feed ration and the time of blood sampling
      on the Lactate Dehydrogenase (LDH)-Isoenzyme pattern in the blood serum of
      "Thessaloniki" crossbred type lambs was examined. For this purpose 24 lambs, 45
      days old, were randomly allocated in three groups (8 animals each group). The
      lambs were (after weaning) fed by rations differing in energy content. (Gruppe A:
      12.0 MJ, M.E./kg, Gruppe B: 10.8 MJ, M.E./kg, Gruppe C: 9.9 MJ, M.E./kg). For the
      estimation of the main effects and interactions a least square analysis was
      applied. The effect of the energy level upon the relative distribution of LDH
      Isoenzymes in the serum of lambs was significant only for the enzymes LDH1 and
      LDH5, between the groups A and C. As to the effect of time of blood sampling
      there were significant differences in all isoenzymes. The interaction "ration X"
      "time of blood sampling" was only significant for LDH1-isoenzymes.

PMID- 9528204
TI  - [Thrombosis, LES, antiphospholipid antibodies: a case report].
AB  - The association between venous deep thrombosis and the presence in circle of
      antiphospholipid antibodies in a patient affection from LES has prompted the
      authors to any considerations on the physiopathology and the therapy of an
      identified syndrome recently, of big clinical interest and surely not frequent in
      the departments of inside medicine. The authors also review the literature on the
      subject.

PMID- 9528207
TI  - [Continuation of the observation and serological investigation of a Maedi-Visna
      virus infected sheep flock from January 1990 to June 1996].
AB  - This paper describes the second part of a longtime-study, started in 1987.
      Serologic investigations for detecting antibodies against Maedi Visna-virus (MVV)
      were performed, involving an institute own sheep flock. The method used was the
      immunodiffusiontest. The flock consisted of different breeds and their
      offsprings. So far, the virus seems to persist in the herd. This work also shows
      the importance of the central role of the does for spreading the virus.
      Seroconversion was detected in a sheep at the age of 32 months. The mother of
      this sheep was a thoroughbred and MVV-negative mountain sheep. After removal of
      the animals with high antibody (ab)-titers, until the end of 1991, the percentage
      of seronegative sheep increased. Then seropositive sheep didn't show high ab
      titers anymore. Since 1990 only offsprings increased the size of the herd. The
      health status of the flock was clinically inconspicuous. It can be concluded that
      in spite of good food quality, good hygiene, without culling positive animals and
      just giving away accidentally some sheep, no elimination of MVV was registered in
      the flock over a period of more than six years. There was only seen a reduction
      of seropositive animals. Single results of serological tests, without knowing the
      sheep and the serological status of the herd, could pretend a false negative
      status.

PMID- 9528208
TI  - [Estimation of body composition based on total body water determination using
      phenazone for assessment of body fat gain in cattle. 2. Relationship between body
      fat content and back fat thickness].
AB  - Back fat thickness was measured at six points in 251 beef heifers aged 3 to 17
      months, in 27 beef bulls aged 15 months and in 200 Holstein dairy cows of
      different age. This was paralleled by estimation of body fat content based on
      total body water analysis. All groups of animals showed the same pattern of back
      fat thickness for the measuring points investigated, which lead to the result of
      one optimum measuring point for determination of back fat thickness. The
      correlation coefficients between back fat thickness and body fat content were
      estimated to be between 0.80 and 0.87 for all groups investigated. Change in back
      fat thickness by 1 mm corresponded to gain or loss of around 5 kg body fat in all
      animal groups. Therefore it is possible to make concrete assessments of body fat
      content on the basis of back fat thickness.

PMID- 9528209
TI  - [Determination of fibrinogen levels in the horse with the heat-precipitation
      methods of Schalm and Millar].
AB  - The purpose of this study was to investigate the usefulness of two heat
      precipitation techniques (Schalm- and Millar-method) as screening tests to
      measure plasma fibrinogen concentration in horses. Based on the measurement of
      samples from 108 different horses, the coefficient of correlation (CC) for the
      relationship between the results with the Schalm- and with the reference-method
      (Jacobsson) were much lower (r = 0.78) than between the Millar- and Jacobsson
      method (r = 0.94). Furthermore the Schalm-method was less precise as reflected by
      the greater coefficient of variation (CV, within-run precision) with a sample of
      low-limit fibrinogen concentration (CV = 47.4 %) and with a sample of high
      fibrinogen concentration (CV = 35.6 %) than the Millar-method (CV = 11.1 resp.
      2.9 %). In 40 healthy horses, aged 3 to 19 years, fibrinogen values ranged from
      1.82 to 4.94 g/l (2.5-97.5 %-quantil). The Millar-Method is recommended as a
      simple and suitable heat-precipitation assay for fibrinogen determination in the
      horse.

PMID- 9528210
TI  - [Histologic studies on the corpora amylacea in the mammary glands of goats,
      horses, and ewes].
AB  - Corpora amylacea are present in all the mammary glands of the investigated
      animals (ewe, goat, and mares). Generally, they are comparable to the cow
      regarding to its distribution, frequency, size, morphological structure, and
      staining properties. Corpora amylacea occur most frequently in the ewe, and in
      non-lactating mammary glands. In lactating mammary glands they are mostly
      situated in the alveoles. During gestation they are located outside of the
      alveoles and in the interalveolar connective tissue. Only in very few cases
      corpora amylacea are found inside and outside of the alveoles in the same mammary
      gland. Frequently, its centre consists of a round nucleus.

PMID- 9528211
TI  - [Appropriateness of animal rights in housing conditions in animal husbandry of
      domestic animals].
AB  - Along with a general redirection of values in agriculture, the need for action
      arises for veterinary medicine and other life sciences to establish suitable
      tools for the objective assessment of housing conditions with regard to their
      appropriateness concerning animal welfare. First communication between the
      disciplines involved demands a uniform use of terms. Assessment can be carried
      out generally either directly by using pathological, physiological and
      ethological reactions of the animals as criteria or indirectly by the means of
      technical criteria. Both approaches can indicate poor or good conditions with
      regard to animal welfare and are generally agreed upon. However using these
      measures in practise often yields problems referring to the methodology and to
      the results that are hard to interpret. Criteria referring to the state of the
      animals have a reduced meaningfulness due to the following aspects: A lot of
      criteria are lacking sensibility and specificity, which leads to a small
      diagnostic selectivity. A large number of sources for variance aggravate the use
      of reference values in order to distinguish between normal or abnormal levels. In
      many cases there is a lack of firm evidence that the level of changes correlates
      with the health and welfare of the animals. Due to contradictions caused by the
      differing properties of the variables being measured the measures do not always
      co-vary. Results and conclusions of the assessments are closely connected to the
      specific experimental design and cannot easily be transferred to the housing
      conditions in practice showing a large variance. Therefore criteria referring to
      the animals can be used primarily for the assessment of standardized or serial
      produced housing systems, where a direct comparison between systems is
      permissible. In order to find out the weak points of the housing conditions
      concerning animal welfare, on-farm assessment can be carried out more
      advantageous by using design criteria. Those criteria can be divided into
      structural and technical elements on the one hand and management born factors
      like hygiene, climate and feeding on the other. The use of structural and
      technical elements as criteria ensures a high level or repeatability of the
      results and practicability in the application. However, a confinement to
      structural and technical elements went along with a marked reduction in the
      meaningfulness of the assessment. The use of management born factors is governed
      by the specific situation. The variation of results depend to a high degree on
      the time of evaluation. Statements of the real situation within a longer period
      of time therefore require great efforts. Due to the complex phenomenon there is
      justified concern that a comprehensive assessment and conclusion referring to the
      appropriateness of housing conditions concerning animal welfare is not possible.
      Few criteria cannot be equated with the whole. However, partial statements can be
      achieved under a scientific point of view using a mixture of different criteria.
      In order to integrate and weigh the varied results reached by different criteria,
      a systemic approach and an integrative way of diagnosis is needed. Up to now
      there is a lack in matured concepts that put the integrative approach of
      assessment into practice.

PMID- 9528212
TI  - [Peripartum myocardiopathy. A case report, diagnostic and therapeutic
      considerations].
AB  - A case of periobstetric cardiomyopathy is presented, it was identified at 32
      weeks, because of congestive cardiac failure, the obstetric event was resolved by
      cesarean section due to low fetal reserve, clinical and hemodynamical criteria
      for diagnosis are reviewed and also therapeutic alternatives are discussed.

PMID- 9528213
TI  - [HELLP syndrome. Hepatic subcapsular hematoma and infarction. 2 cases reports].
AB  - Two patients with HELLP syndrome are presented and hepatic subcapsular haematoma
      and infarction were documented. The first clinical manifestation in both cases
      was hypotension. A surgical pregnancy interruption was required. These patients
      also presented leukocytosis, renal insufficiency, severe hepatic failure and the
      presence of hepatic encephalopathy (grade III-IV). One patient died in spite of
      medical intervention with multiple organ failure. The other patient is still
      alive but with minor liver dysfunction.

PMID- 9528214
TI  - [AIDS and pregnancy].
AB  - Near 70 per cent of Mexican women infected by the Human Immunodeficiency virus
      (HIV) are between 15 and 44 years old, in this women sexual transmission are the
      most frequent route of infection. The objective of this article was to describe
      the obstetric course and perinatal repercussion of the HIV-Positive pregnant
      women with medical care at the Instituto Nacional de Perinatologia, Mexico city
      between January 1994 to December 1996. Nineteen women were studied, sexual
      transmission was the route of infection in 16 of them. One had diagnostic
      criteria for AIDS, the others 18 had HIV asymptomatic infection. At delivery 18 a
      term products were born. The mean of the newborn weight was 3159 g. At moment of
      this report 4 children (22%) have been diagnosed as HIV infected, all of them
      dead during their first year of life.

PMID- 9528215
TI  - [Conservative laparoscopic treatment of bilateral ectopic pregnancy. 2 case
      reports and review of the literature].
AB  - Ectopic pregnancy is a frequent clinic entity, with an incidence from 4.5 to 16.8
      for 1000 pregnancies. The frequency of ectopic pregnancy has been triplicated in
      the last years, mainly owed to increase of sexual transmitted diseases, increase
      in salpinges' surgery and in assisted reproductive medicine. The ectopic
      pregnancy is also the most frequency cause of maternal death during the first
      trimester of pregnancy. The frequency of bilateral tubal ectopic pregnancy is
      extremely rare, it is reported from 1:125 to 1:1580 of all ectopic pregnancies.
      The first case of bilateral tubal ectopic pregnancy was reported n 1918 by
      Bledsoe. In Mexico, Molina described the first case in 1993, with conservative
      laparoscopic treatment. Two clinic cases are presented of bilateral ectopic
      pregnancy, treated conservatively by laparoscopy. The first one with background
      of sterility because of anovulation, receiving treatment with menotropins for
      ovarian hyperstimulation, the other one. In the second case, was a spontaneous
      pregnancy, in a patient with a history of several pelvic surgeries. In this case
      a bilateral salpingostomy was realized. In both cases was demonstrated chorionic
      villi by histopathology. These cases are a model of nature to evaluate the real
      utility of several diagnostic and therapeutic methods which are available
      nowadays for the treatment of ectopic pregnancy.

PMID- 9528216
TI  - [Antiphospholipid antibody syndrome, molar pregnancy and cerebral infarct. A case
      report].
AB  - The clinic case of a 14 years old patient, with a molar pregnancy, hypertension
      and ischemic cerebral arrest in the temporoparietal left region is being
      described. Lupus anticoagulant antibodies were determined with a positive result
      corresponding with a clinic scheme to an antiphospholipid antibodies which is
      clinically associated with occlusive venous or arterial disorders in several
      regions, as well as deeply venous thrombosis in the extremities, brain, lungs and
      recurrent loss of early pregnancy, severe preeclampsia with an early appearance
      and fetal growth retardation.

PMID- 9528217
TI  - [True hermaphroditism with bilateral ovotestis].
AB  - A nineteen years old woman with ambiguous external genitalia was studied. This
      condition had been previously identified as a newborn, but her parents refused
      medical attention and it was reared as a girl. At 12-years, she began spontaneous
      mammary development, appearing pubic and axillary hair, and clitoral enlargement.
      The menarche occurred at 15-years and it was followed by irregular periods.
      Physical examination, showed absence of hirsutism and acne, normal mammary
      development equivalent to grade V of Tanner. The external genitalia showed fused
      labio-scrotal folds with an small introitus. The urethral meatus was absent and
      was later located inside the introitus. There was a big phallus similar to an
      adult penis with a normal glans, flexed by a chordee. Hormonal determinations
      discarded congenital adrenal hyperplasia. The karyotype was 46,XX and
      testosterone levels were in adult male range. Pelvic ultrasonography disclosed a
      normal uterus and both gonads in confirmed by laparoscopy identifying bilateral
      ovotestis. Testicular tissue was removed and plastic reconstruction of female
      genitals was done.

PMID- 9528218
TI  - [Female pseudohermaphroditism. Mixed germ cell tumor of the ovary. A case
      report].
AB  - It is known as Pseudohermaphroditism or intersexual state, those entities in
      which external genitalia are ambiguous or are not according with gonadal o
      genetic chromosomic sex. They can have diverse etiology. Continual exposition to
      estrogens or androgens may induce female or male dysmorphism, and also
      development of benign or malignant tumors at target organs. We present a case of
      a young woman, 15 years old, with virilization, who attend medical consultation
      for progressive abdominal growing. The presence of ambiguous, genitalia since
      birth, was not a previous reason of concern. Diagnostic, findings, management and
      follow up for about 4 months are described and also a topic review. Genitalia
      develop during first trimester of intrauterine life, under influence of sexual
      steroids, and changes of sexual development can emerge as consequence of
      endocrine or morphologic disorders and the later ones, related to karyotypic
      abnormalities. Sexual steroid and their metabolites can demonstrate individually,
      different biological effects, suggesting the presence of individual receptors.
      The presence of cooperative effects between each steroid produce even more
      complexity to the evaluation of each steroid. Various mutations principally at
      gene receptors of sexual steroids, cause resistance to them. At female
      pseudohermaphroditism in difference from male P. there is no errancy at genetic
      gonadal transmission. These women are intrauterine exposed to excessive
      quantities of androgens, and they have normal internal genitalia but external
      ambiguous genitalia. The involved androgen comes from external factors, a it
      occurs at mother who receives progesterone to avoid abortion, but it is due
      frequently to androgen storage, caused by enzymatic blockade at steroidogenesis
      (adrenogenital syndrome).

PMID- 9528219
TI  - [Costs of maternal-infant care in an institutionalized health care system].
AB  - Partial and total maternal and child health care costs were estimated. The study
      was developed in a Primary Care Health Clinic (PCHC) and a General Hospital (GH)
      of a social security health care system. Maternal and child health care services,
      type of activity and frequency utilization during 1995, were defined; cost
      examination was done separately for the PCHC and the GH. Estimation of fixed cost
      included departmentalization, determination of inputs, costs, basic services
      disbursements, and weighing. These data were related to depreciation, labor
      period and productivity. Estimation of variable costs required the participation
      of field experts; costs corresponded to those registered in billing records. The
      fixed cost plus the variable cost determined the unit cost, which multiplied by
      the of frequency of utilization generated the prenatal care, labor and delivery
      care, and postnatal care cost. The sum of these three equaled the maternal and
      child health care cost. The prenatal care cost was $1,205.33, the labor and
      delivery care cost was $3,313.98, and the postnatal care was $559.91. The total
      cost of the maternal and child health care corresponded to $5,079.22. Cost
      information is valuable for the health care personnel for health care planning
      activities.

PMID- 9528220
TI  - [Brain damage following aortic arch repair with regard to techniques of selective
      cerebral perfusion and preoperative cerebral lesions].
AB  - One hundred and twenty-nine aortic aneurysm patients (true 68 and dissection 61)
      underwent aortic arch repair from January 1987 to December 1995. Postoperative
      brain damage was evaluated regarding both preoperative brain lesions and
      techniques of selective cerebral perfusion (SCP) in that one pump for SCP until
      April 1992, then two pumps were employed, one for right and the other for left
      hemisphere of the brain. Overall hospital mortalities were 21% in true and 13% in
      dissecting aneurysms. Ten patients were complicated with postoperative brain
      damages (coma 8 and hemiplegia 2), registering 7.8% of total patients. Both
      history of stroke and silent cerebral infarction (SCI) detected by CT and/or MRI
      were considered to be positive in the mean of having preoperative brain lesions.
      Although there was no significant difference between incidences of postoperative
      brain damage in true and dissecting aneurysms, registering 11% and 4%
      respectively, preoperative brain lesions in true aneurysm (68%) was significantly
      greater than dissecting aneurysm (32%). Furthermore, the incidence of
      postoperative brain damage was 22% in one-pump SCP which was significantly
      greater than 3% in two-pumps SCP in the patients with a true aneurysm. But there
      was no postoperative brain complication in patients with SCI even using either
      one two pumps for SCP. The present data suggest two-pumps SCP is better technique
      for cerebral protection compared to one-pump SCP for aortic arch repair.

PMID- 9528221
TI  - [The left ventriculectomy (Batista procedure) in a patient of the dilated
      cardiomyopathy: a report of the first successful case in Japan].
AB  - We presented a case of 18-year-old male with dilated cardiomyopathy undergoing
      surgical left ventricular volume reduction (Batista procedure). He seemed to be
      the first successful survivor after the procedure in Japan. In the follow up
      study, cardiac function and clinical status of the patient have been moderately
      improved. Batista procedure seems to be an attractive choice to treat end-stage
      heart failure in Japan where the option of treatment for this particular
      situation is limited.

PMID- 9528222
TI  - [An experience with peeling technique with curettage of open mitral
      commissurotomy].
AB  - Ideally, the mitral valve is a soft, thin and flexible tissue. In severe
      rheumatic mitral stenosis, however, its motion is restricted due to the adhesion
      of fibrous tissues and calcium. Open mitral commissurotomy was not effective in
      successfully restoring it to normal condition. By using a peeling technique with
      curettage during open mitral commissurotomy, the calcium and fibrous tissues are
      sufficiently removed. This method is effective in improving the flexibility of
      the anterior leaflet of the restricted mitral valve.

PMID- 9528223
TI  - [Current topics of coronary artery bypass surgery in Japan].
AB  - Recently, the number of patients with atherosclerosis has been rapidly increased
      in Japan. However, there are many kinds of resolving problems for management of
      those patients. Here history and current topics of coronary artery bypass
      grafting (CABG) in Japan are clearly documented. That is, CABG could be done in
      48,612 cases during the past 5 years (1991-1995). And its mortality rate was 2.3%
      approximately. On the other hand, 12,025 underwent CABG in 1996 in Japan. Further
      several kinds of operative methods including MIDCAB have been carried out with
      the number of the patients with ischemic heart diseases. Excellent results have
      been obtained respectively.

PMID- 9528224
TI  - [Thoracoscopic repair of diaphragmatic eventration sustained at knife injury: a
      case report].
AB  - A 46-year-old male taxi driver was stabbed onto the left chest while on duty. On
      arrival soon after, he was hemodynamically stable. Computed tomography showed
      omental prolapse into the left thorax through the diaphragm. On the 11th day, he
      underwent thoracoscopy revealing omental prolapse via a 3-cm rent in the left
      diaphragm, which was reduced manually. The diaphragmatic orifice was lifted and
      debrided with suturing using a stapling cutter. The post-operative course was
      uneventful. Finger palpation through the orifice enabled safe suturing of the
      left diaphragm facing the omentum, the colon, and the stomach, all of which may
      suffer iatrogenic injury.

PMID- 9528225
TI  - [Surgery for the treatment of infective endocarditis in the active and inactive
      stages].
AB  - Twenty-eight patients (16 M, 12 F, age 11 approximately 72 yr, mean 52.8 yr)
      underwent surgery for infective endocarditis. Of the 27 patients, 16 were in the
      active stage and 11 were in the inactive stage. In patients in the active stage,
      aortic valve replacement (AVR) was performed in 5, mitral valve replacement (MVR)
      in 7, AVR + MVR in 1, AVR + MVR + tricuspid valve plasty (TVP) in 1 and other
      procedures in 2. In patients in the inactive stage, AVR was performed in 3, MVR
      in 4, AVR + MVR in 2, and other procedures in 2. Causative organisms were
      detected in 56.3% of the patients in the active stage and 54.5% in the inactive
      stage. Also in patients in the active stage, infection was not prolonged. No
      deaths occurred among patients in the inactive stage but five patients (31%) died
      postoperatively; 4 of the five also died, for had severe heart failure before
      surgery, three died of multiple organ failure and one died of subarachnoid
      hemorrhage due to infective aneurysm. We recommend surgery for the treatment of
      infective endocarditis even in the active stage before emergence of heart
      failure.

PMID- 9528226
TI  - [Surgical technique of endoscopic transthoracic sympathicotomy: axillary
      approach].
AB  - A total of 181 endoscopic transthoracic sympathicotomy were performed at our
      hospital from December, 1992 to March, 1997. After single-lumen endotracheal
      intubation for general anesthesia, the patient was placed in half sitting
      position. A small (1 cm) incision was made in the anterior axillary line through
      the third intercostal space and an apical pneumothorax was created by
      insufflation of 1.8 L of CO2 in the pleural cavity through a Surgineedle. A 24
      Fr. urological transurethral electroresectoscope was introduced through the same
      incision. The sympathetic chain could be observed through parietal pleura riding
      on the costovertebral junctions. In palmar hyperhidrosis the second and third
      thoracic sympathetic ganglia were electrocoagulated. In axillary hyperhidrosis
      the forth ganglion was included. The lung was expanded by limiting expiration and
      sucking CO2. The operation was repeated on the other side. Endoscopic
      transthoracic sympathicotomy was an efficient, safe and low invasive surgical
      procedure for the treatment of palmar, axillary hyperhidrosis, Raynaud's disease
      and Buerger disease.

PMID- 9528227
TI  - [A case of the atrial dissociation after maze procedure: the coexistence of the
      sinus node potential and the focal atrial potential in high right atrium].
AB  - In a 58-year-old man, who was suffered from atrial fibrillation for a period of
      20 years due to mitral stenosis and aortic valve regurgitation, mitral and aortic
      valve replacement and maze procedure were underwent. We have, whenever possible,
      substituted the cryoablation for the incision in the maze procedure in attempt to
      prevent massive bleeding. We found the oscillation of the baseline in lead I, II,
      III, aVL, aVF on postoperative surface electrocardiogram. We recognized the
      coexistence of 90/min sinus node potential and 375/min independent focal atrial
      potential in high right atrium (HRA) of intra-cardiac recording and only the
      sinus node potential in middle and lower right atrium of that. It was thought
      that the incision of maze procedure and cryoablation occurred to the atrial
      dissociation which coexisted segmental atrial fibrillation and sinus rhythm by
      electrophysiological block. In the postoperative electrophysiological study the
      sinus node automaticity and sinoatrial conduction were within normal limit and
      atrial tachycardia and atrial fibrillation were not induced. A wave of both atria
      was recognized in transesophageal echocardiography, though the segmental atrial
      fibrillation was left in a small region of HRA. It was supposed to be useful for
      maze procedure at the point of cardiac function, which included the maintenance
      of sinus rhythm with segmental atrial fibrillation, atrial kick and the recovery
      of the atrio-ventricular synchrony.

PMID- 9528228
TI  - [A surgical case of quadricuspid aortic valve associated aortic regurgitation and
      severe mitral regurgitation due to infective endocarditis].
AB  - We report a case of rare anomaly of quadricuspid aortic valve associated aortic
      regurgitation and severe mitral regurgitation due to infective endocarditis. A 50
      year-old man was admitted to our hospital for fever and dyspnea. The
      transesophageal echocardiography showed severe aortic regurgitation due to four
      equal aortic cusps and severe mitral regurgitation due to infective endocarditis.
      At the operation, aortic valve and mitral valve were replaced with 23 mm and 29
      mm SJM valves. His postoperative course was uneventful.

PMID- 9528229
TI  - [A case report: right ventricular outflow tract (RVOT) reconstruction using
      homograft for RVOT restenosis after Jatene's procedure of transposition of the
      great arteries (TGA)].
AB  - A 7-year-old boy was admitted for RVOT restenosis. The patient was born following
      an unremarkable pregnancy and delivery. He was carried out Jatene's procedure for
      TGA at 23rd day after birth. At 19 month of age, he was removed pulmonary
      stenosis using patch angioplasty with mono cusp. When he was 6 year of age, the
      onset of edem, ascites and hepatomegaly were pointed out. At 7 year of age, he
      was admitted for edema, hypoproteinemia and protein loosing enteropatchy. After
      he was treated medical therapy, cardiac catheterization showed markedly right
      atrial and right ventricular hypertension and ventricular septal defect (VSD).
      Cine angiography suggested the right ventricular outflow tract stenosis,
      pulmonary valve and tricuspid valve insufficiency. On August 1, 1996, the patient
      underwent surgical repair: direct closure of VSD, aortic homograft (20mm)
      replacement for RVOT stenosis and tricuspid valve annuloplasty by DeVega's
      procedure. Postoperative course was uneventful. At 23rd postoperative day,
      cardiac catheterization and cine angiography showed no problems. He was not
      treated with anticoagulation.

PMID- 9528230
TI  - [A case of painless Standford type A acute aortic dissection complicating acute
      occlusion of the right subclavian artery].
AB  - We reported about a rare case of painless Stanford type A acute aortic dissection
      with the only complaints being numbness and paleness in the right arm. A 68-year
      old male who hed been treated in another hospital under the diagnosis of acute
      occlusion of the right subclavian artery was referred to our hospital because of
      severe heart failure and shock. After being admitted to our hospital, the patient
      was diagnosed as Standford type A acute aortic dissection with transesophageal
      echocardiography and underwent an emergency graft replacement of the ascending
      aorta and total aortic arch. The postoperative course was uneventful and the
      patient was discharged without any complications.

PMID- 9528231
TI  - [A case of surgical treatment for giant pseudoaneurysm of the left ventricle
      after myocardial infarction].
AB  - A 70-year-old male was admitted for acute postero-inferior myocardial infarction.
      In cardiac catheterization one month later, there was narrowing of the distal
      left circumflex artery and the aneurysm of the postero-inferior wall of the left
      ventricle. The echocardiogram strongly suggested the pseudoaneurysm of the left
      ventricle. At operation, a large postero-inferior aneurysm was densely adherent
      to the pericardium. After cardiopulmonary bypass was established, the aorta was
      cross-clamped and cold cardioplegia was infused, the aneurysm was opened without
      excision of it. There was a 4 cm by 5 cm defect in the postero-inferior wall of
      the left ventricle, which communicated with the cavity of the aneurysm. The
      defect was closed with a patch. Pseudoaneurysm of the left ventricle was
      diagnosed by histological examination. The postoperative course was uneventful
      and he discharged on 29th day after surgery.

PMID- 9528232
TI  - [Successful chemotherapy based on in vitro chemosensitivity testing in a case of
      recurrent thymic carcinoma].
AB  - A 71-year-old woman underwent radical resection in May 1994 for a mediastinal
      mass invading the anterior chest wall. Histopathological examination revealed
      adenosquamous cell carcinoma. She was treated with postoperative chemotherapy
      including 5-fluorouracil (5-FU) and 4'-D-tetrahydropyrayl-doxorubicin (THP),
      based on in vitro chemosensitivity testing (CST), by MTT assay, using a surgical
      specimen. In December 1994, a recurrent tumor was detected on the left anterior
      chest wall and the patient received two courses of 5-FU, THP and methotrexate
      (MTX). The size of the chest-wall tumor decreased 25%. In July 1995, the patient
      had involvement of the left axillary lymph node and brain metastases in addition
      to the mass on the chest wall. Therefore, cisplatin, 5-FU and MTX were selected
      as treatment agents, based on CST using a metastatic axillary lymph node. After
      two courses of these agents, chest computed tomography showed a 91% reduction in
      the size of the chest wall tumor. Radiation was administered for the brain
      metastasis. In March 1997, the patient died of thymic carcinoma.

PMID- 9528233
TI  - [A case of inflammatory pseudomotor of the lung suspected of being metastasis of
      thymoma].
AB  - An operated case of inflammatory pseudotumor of the lung is reported. A 27-year
      old female was pointed out a coin lesion in the left lower lung field on chest X
      ray and the size of mass increased. She had a history of thymomectomy for
      thymoma, and resection of right intrathoracic dissemination. Therefore operation
      was performed on suspicion of metastasizing thymoma. A partial resection
      including the mass with VATS was performed and histopathologic examination
      revealed inflammatory pseudotumor. The postoperative course was uneventful, and
      there has been no evidence of recurrence thereafter. In Japan, sixty-eight cases
      of inflammatory pseudotumor of the lung including our case have been reported in
      the literature.

PMID- 9528234
TI  - [Lung laceration caused by penetrating chest wall injury in Hanshin & Awaji
      earthquake: a case report].
AB  - A 36-year-old man having a left lower lobe laceration caused by penetrating chest
      wall injury was operated on 5 hours after Hanshin & Awaji Earthquake. At
      thoracotomy, significant destruction of the left lower lobe was observed.
      Therefore, we gave up repairing a lung, and performed left lower lobectomy, with
      a satisfactory outcome. Our hospital is located on 30 km south of seismic center,
      but the function of our hospital was not completely paralyzed. In Awaji island,
      emergent treatments were done satisfactorily.

PMID- 9528235
TI  - [A case of nodular fasciitis of the chest wall].
AB  - We present a case of nodular fasciitis of chest wall origin. A 62-year-old woman
      visited our hospital because of a rapidly growing hard tumor fixed to her right
      chest wall, measuring 7 x 8 cm in size. Although incisional biopsy specimen
      revealed that the tumor was suggestive of nodular fasciitis, the possibility that
      the tumor had a malignant component could not be excluded. Total excision of the
      mass with combined resection of 3rd, 4th, 5th ribs was performed to establish the
      histological diagnosis and treatment plan. We believe that the tumor proved to be
      malignant by excisional biopsy, should then undergo further excision with
      sufficient surgical margin. Nodular fasciitis may be misdiagnosed as a sarcoma
      due to its rich cellularity, mitotic activity and poorly circumscribed nature.
      Awareness of the histological features of nodular fasciitis, and its predilection
      for presenting as a rapidly growing mass, should decrease the likelihood of
      misdiagnosis and the attendant risk of over surgery.

PMID- 9528236
TI  - [An operative case of primitive neuroectodermal tumor in the posterior
      mediastinum].
AB  - A primitive neuroectodermal tumor (PNET) is very rare and the prognosis of this
      tumor is poor. A 32-year-old woman complaining of dysphagia and back pain was
      admitted to our hospital for the posterior mediastinal tumor. The tumor
      originated from the muscle layer of esophagus and en bloc resection of the tumor
      combined with the affected part of esophagus was performed. Histopathological
      diagnosis of the resected tumor was PNET. She received adjuvant chemotherapy.
      Eight months after the surgery, recurrent tumors in the right mediastinum and the
      retrooperitoneal space was resected completely. But after the second surgery,
      dissemination occurred recurrently. These recurrent tumors revealed high
      sensitivity for radio-therapy. However, she died of rapid recurrence 22 months
      after the first surgery. In Japan, our case is the second case of PNET in the
      posterior mediastinum and the first case of PNET arising from the muscle layer of
      esophagus.

PMID- 9528237
TI  - [A case of acute empyema who underwent omentopexy and was found to have gastric
      cancer during operation].
AB  - A 76-year-old man had undergone omentopexy for empyema. He was found to have
      gastric cancer and revealed Borrmann III by gastroendoscopy intraoperative
      period. Segmental gastrectomy was performed without dissection of lymph nodes,
      because his general condition was poor. After operation, the patient showed
      septic shock, ARDS and hepato-renal failure but his condition was getting
      improved by conservative therapy. After 5 years later, he was examined gastro
      endoscopy, abdominal and chest CT and revealed no recurrence sign.

PMID- 9528238
TI  - [A case of traumatic lung cyst].
AB  - Traumatic lung cyst is an uncommon lung injury due to closed chest trauma. A 5
      year-old boy was admitted to our hospital after being run over by motor vehicle.
      Computed tomography of the chest demonstrated multiple cystic lesions. This case
      was diagnosed as traumatic lung cysts. Computed tomography taken 37 days after
      initial injury showed complete resolution of the cysts. Computed tomography was
      useful in diagnosing traumatic lung cyst and following its clinical course.

PMID- 9528239
TI  - [Breast cancer care program should be revised. New knowledge about diagnosis and
      treatment is needed].

PMID- 9528240
TI  - [A new series: cross-cultural care. How do health care services manage
      immigrants' problems?].

PMID- 9528241
TI  - [The genes behind diabetes. Research in developmental biology may result in
      improved therapy].

PMID- 9528243
TI  - [Internet and e-mail: "hot lines" for the public].

PMID- 9528244
TI  - [Free of charge health service are a burden to the departments].

PMID- 9528245
TI  - [Adaptogenes and stress--a short comment].

PMID- 9528246
TI  - [Prejudices on efficiency of Swedish health care].

PMID- 9528247
TI  - [Prescription rules disrupt a sensitive relation].

PMID- 9528248
TI  - [Swedish migration in a current, historical and international perspective:
      immigration put more demands on health care].
AB  - Sweden will soon have a million foreign-born residents, representing almost 11
      per cent of the population. As shown in the article, migration to Sweden is a
      continuing process rather than an isolated life event; for example, half of those
      who emigrated to Sweden in 1968 had returned to their home country or proceeded
      to a new country by 1988. The possible effects of the migration process upon
      immigrants, and the ensuing impact on primary health care, are examined in the
      article. Published findings suggest that immigrants--whether they migrate because
      of war, political or religious persecution, or for economic reasons--may
      experience increased stress, thus exacerbating any individual susceptibility to
      illness. Strategies for future research in migration medicine and primary health
      care are also discussed.

PMID- 9528249
TI  - [Somatic health is poorer among foreign-born than native Swedes].
AB  - In a study based on data derived from the Swedish Survey of Living Conditions
      conducted from 1990 to 1993, differences in the prevalences of long-term somatic
      illnesses between native and foreign-born Swedes were analysed. Of the 18,242
      randomly selected participants, aged 25-74 years. Eleven per cent were foreign
      born, a figure consistent with the proportion of immigrants in the population as
      a whole. For the purpose of analysis, the foreign-born participants were divided
      into four subgroups: Finns, Southern Europeans, those from Western countries, and
      all others (i.e. from East Europe, Asia, Africa, and Latin America). As compared
      with native Swedes, and after adjustment for sex, age, marital status and level
      of education, the Finnish, Southern European and 'all other' subgroups were
      characterised by significantly higher prevalence rates for for longterm somatic
      illness (odds ratios, 1.62, 1.49 and 1.24, respectively). The same three
      subgroups also manifested significantly higher age- and sex-adjusted prevalences
      of musculo-skeletal diseases. Although the study design did not permit
      determination of whether susceptibility to poor somatic health was exacerbated by
      migration trauma or acculturative stress, the results suggest immigration to have
      an adverse effect on health.

PMID- 9528250
TI  - [The Solhemmet--a progressive initiative for Sophia-nurses].

PMID- 9528251
TI  - [Policy program to minimize spread of infection. Prolonged cough may be a sign of
      tuberculosis].
AB  - In a worldwide epidemiological perspective, Sweden is well favoured with an
      annual tuberculosis incidence of approximately six cases per 100,000 of the
      population. Neither the impact of the HIV pandemic nor the occurrence of
      multiresistant strains of Mycobacterium tuberculosis has yet become a major
      problem in the care of tuberculosis patients in Sweden. Only a few per cent of
      HIV patients have developed tuberculosis, and during the period, 1991-94, only
      one per cent of M. tuberculosis isolates in Sweden were resistant to such
      antimycobacterials as isoniazid and rifampicin. However, the epidemiological
      situation in the neighbouring Baltic states is a matter for concern. Bovine
      tuberculosis has been eradicated in Sweden, the last case having been diagnosed
      in 1978. Although the reported efficacy of BCG (bacillus Calmette-Guerin)
      tuberculosis vaccine varies according to the population studied, protective rates
      of 70-85 per cent have been reported for Sweden and other west European
      countries. Re-vaccination of tuberculin-negative individuals has not been shown
      to yield added protection. The aim of a national programme for protection against
      tuberculosis is to preserve our favourable epidemiological situation by early
      detection of new cases, effective contact tracing, and BCG vaccination of
      children in population groups at risk. The primary means of achieving this is the
      education of health care personnel to retain tuberculosis as a differential
      diagnosis. Moreover, national guidelines for contact tracing must be duly
      observed, and immigrants from high prevalence areas need to be screened for
      tuberculosis. Registration of all cases of tuberculosis should be maintained at
      regional and national levels, and follow-up must be meticulous until a successful
      outcome of treatment is accomplished. Recommendations for dealing with
      tuberculosis should be made available and duly implemented at all hospitals
      caring for tuberculosis patients, in order to avoid nosocomial transmission.
      Although BCG vaccination at birth was formerly general in Sweden, since 1975 only
      children considered to be at risk have been vaccinated. Thus, non-vaccinated
      young adults are now entering the health care sector as students or employees,
      and should be offered BCG vaccination. Moreover, the epidemiological situation
      both in Sweden and in neighbouring countries needs to be monitored carefully in
      order that recommendations concerning BCG vaccination and other preventive
      measures can be modified if necessary.

PMID- 9528252
TI  - [Knowledge about crime victims should be included in medical and nursing
      education].

PMID- 9528253
TI  - [Report from Chechnia. Psychiatry without resources in a traumatized coutry].

PMID- 9528254
TI  - [Experts ask for priorities when it comes to interpretation. Ravnskov answers in
      the debate on dietary fats].

PMID- 9528255
TI  - [Diagnosis of dyslexia is often very much delayed. A retrospective study of 102
      pupils].

PMID- 9528256
TI  - [Why is doctor Jekyll a physician? ...and how closely related is he to
      Frankenstein?].

PMID- 9528257
TI  - [Medical education in the United Arab Emirates. Radiology is integrated into the
      entire basic curriculum].

PMID- 9528258
TI  - [Immunotoxicity of beryllium].
AB  - The lymphocyte transformation test and the macrophage migration inhibition test
      are quantitative methods invaluable for examination of beryllium (hereafter
      referred to as Be) effects on cell-mediated immunity. We recognized that the Be
      sensitizing ability was related to active as well as passive cell-mediated
      immunity in mice subcutaneously injected with Be once a week over a 6-week
      period. Be also affects B cells, and it increases the amount of immunoglobulins
      in sera. In the study of immunological health surveys of Be workers in a copper
      beryllium casting factory, the serum complement titer tended to be lower in Be
      workers than in the controls. In mice, injected with Be once a week over a 12
      week period, serum complement titers decreased. Correlation coefficients of the
      experimental parameters showed a significant negative correlation between the
      complement titers and the prothrombin time or the coagulation time for factor
      VII, using mice injected with 5 micrograms of Be. It was suggested that increases
      in the complement titers after Be administration may be induced by temporarily
      activated plasma serin protease, which is a component of blood coagulation factor
      VII. The delta-aminolevulinic acid dehydratase and porphobilinogen deaminase
      activities were significantly elevated in the pregnant untreated group, compared
      with the nonpregnant mice (the control group). However, it was noted that these
      values in the pregnant mice injected with 50 micrograms of Be were almost the
      same as the values of the controls. It suggests that Be suppressed the expected
      pregnancy-induced increase in hematopoietic function. There are at least two risk
      factors induced in the effects of beryllium on organisms-exposure to the metal
      and inheritance of the genetic marker. It is necessary to reduce exposure, to
      give preventive education and to carry out periodic health examinations for the
      prevention of disease induced by Be.

PMID- 9528259
TI  - [HgCl2-induced acute renal failure and its pathophysiology].
AB  - Mercury chloride (HgCl2) has a potent nephrotoxic effect. Most of Hg2+ existing
      in plasma following HgCl2 exposure forms a complex with sulfhydryl-containing
      ligands such as albumin and glutathione (GSH). The Hg(2+)-GSH complex is filtered
      in the glomeruli of the kidney and degraded into Hg(2+)-cysteine in the proximal
      tubules by the combined action of gamma-glutamyl transpeptidase and dipeptidase
      present in the epithelial cells. The degradation product is then incorporated and
      accumulated into the proximal tubule epithelial cells. The accumulated Hg2+ in
      the epithelial cells finally causes acute tubular necrosis (ATN) by its cytotoxic
      effect. At present, it is believed that tubular obstruction resulting from ATN
      triggers the onset of HgCl2-induced acute renal failure (ARF). A progressive fall
      in glomerular filtration rate (GFR) contributes to the progression of HgCl2
      induced ARF. The fall in GFR may be caused by an increment in afferent arteriole
      resistance (RA) and a decrement in the ultrafiltration coefficient (Kf) due to
      mesangial cell contraction. These changes in RA and Kf may be attributed to the
      increased action of the vasoconstrictors, angiotensin II and endothelin-1 and to
      the decreased action of the vasodilator, nitric oxide observed at the glomerulus
      level of HgCl2-induced ARF. Accordingly, the imbalance between these vasoactive
      substances appears to play an important role in the progression of HgCl2-induced
      ARF due to reducing GFR. Further studies, however, remain to elucidate the
      mechanisms involved.

PMID- 9528260
TI  - [An evaluation of the biting force, the body composition and the amount of
      masticatory action in young females].
AB  - The purposes of this study were to investigate factors related to maximum biting
      force and to understand the characteristics of physical properties of daily
      ingested foods in young females. One hundred and forty subjects aged 18-23, with
      Angle 1 class occlusion, had not suffered from periodontitis, and had not been
      treated for preparation of tooth crown of first molars. Body height and weight
      were measured, and percentage of body fat, fat mass (FM) and lean body mass (LBM)
      were estimated, using the impedance analyzer. The maximum biting force was
      measured by the press sensation method. According to the formula on the basis of
      our new version of Yanagisawa's food classification, the mean value of the amount
      of masticatory action for one day was calculated. Subjects were divided into the
      normal biting force and the low biting force groups with -1SD of the maximum
      biting force, in order to compare body composition and backgrounds in sports
      activities between these two groups. Multiple linear regression analysis was
      carried out, employing maximum biting force (kg.f) as a dependent variable, and
      having a background in sports activities, FM, LBM, the number of missing teeth,
      the number of dental caries and the amount of masticatory action for one day as
      independent variables. Results were as in the following: 1) The proportion of
      subjects who had a background in sports activities in the low biting force group
      were less than that in the normal biting force group (p < 0.01). 2) Having a
      background in sports activities and LBM were positively correlated to maximum
      biting force (p < 0.01), while the amount of masticatory action for one day was
      not. 3) All subjects, especially those in the low biting force group seldom had
      food requiring the highest amount of masticatory action. CONCLUSION: Having a
      background in sports activities and LBM are positively correlated with the
      maximum biting force, while the amount of masticatory action for one day was not
      correlated positively nor negatively in young females.

PMID- 9528261
TI  - [Characteristics of medical institutions visited by patients with intractable
      diseases--analyses of patients receiving financial aid for treatment].
AB  - The Research Committee of Epidemiology of Intractable Diseases (Ministry of
      Health and Welfare, Japan) conducted a nationwide survey of 34 intractable
      diseases. Each of 47 prefectural governments reported information on all patients
      with the diseases who received financial aid for the disease from April 1992 to
      March 1993. Information collected on each patient included the identification
      number, sex, age, the code of the municipality where the patient lived, and the
      medical institution and department where the patient was being treated. Out of
      247, 726 patients whose information was reported by prefectural governments, we
      analysed data of 208,945 patients whose medical institutions were reported. The
      results can be summarized as follows: 1) Aged patients and children who were less
      than ten years old tended to visit medical institutions located in their
      neighborhoods and be treated in small hospitals or clinics. 2) The proportion of
      patients who visited hospitals with 200 beds or more was 77 percent. 3) Patients
      with the diseases resulting in physical disabilities such as SMON and malignant
      rheumatoid arthritis tended to visit clinics. Patients with skin diseases as
      pemphigus, epidermolysis bullosa and pustular psoriasis tended to be treated in
      university hospitals. 4) Many patients living in prefectures near large cities
      such as Tokyo and Ishikawa visited medical institutions in the large cities. 5)
      The proportion of patients who visited university hospitals decreased during the
      eight years from 1984 to 1992. However, a quarter of these patients visited
      university hospitals.

PMID- 9528262
TI  - [A study on the effects of physical load placed on high school baseball managers
      during midsummer games].
AB  - We examined the influence of physical load placed on high school baseball
      managers during midsummer games under extremely hot and humid conditions. The
      factors used to determine physical load were the following: body weight, oral
      temperature, amount of walking, pedometer count, heart rate, and serum
      biochemical elements. These factors were measured before and after the games.
      Twenty-two managers participated in this study. All games were played under high
      temperatures of 32.4 +/- 3.5 (mean +/- S.D) degrees Celsius dry-bulb, 27.1 +/-
      3.0 degrees Celsius wet-bulb, 33.8 +/- 3.6 degrees Celsius black-glove, 29.1 +/-
      3.3 degrees WBGT, which are likely to cause heart-related illness. The results
      were as follows. 1. After the games, significant body weight loss and oral
      temperature rise were found. Those findings were thought to be caused by the rise
      in oral temperature in a hot environment which was accompanied by hyperhidrosis.
      2. The average hemoconcentration ratio based on the changes in total protein
      during the games was 105 percent, suggesting that hemoconcentration and
      dehydration were caused by sweating in a hot environment. 3. A significant
      increase in total protein, albumin, LDH, high density lipoprotein cholesterol,
      calcium, hemoglobin, and a decrease in triglyceride were observed after the
      games, which were thought to be influenced by sweating and by increased
      metabolism in a hot environment. 4. The values of triglyceride, Fe, uric
      nitrogen, calcium and hemoglobin after the games which were adjusted by the
      hemoconcentration ratio were significantly lower than those before the games. 5.
      A prolonged game time caused a significant increase in total protein value during
      the games and a decrease in hemoglobin between the level before the games and the
      adjusted level after the games compared with those values in the short game time
      group. From the above, even though high school baseball managers join in
      practices in a hot environment and become accustomed to it, we found that they
      had a great physical load on their bodies during the games in midsummer.

PMID- 9528263
TI  - [Changes of physiological functions in rats induced by immobilization stress].
AB  - A study was conducted on the changes of physiological function in rats due to
      immobilization stress. Male Fischer rats (SPF) of 32 weeks of age were housed in
      individual cages for 4 weeks. Then all rats were immobilized by stainless wire
      mesh for 6 hours daily for 3 days. Blood was collected before the 1st stress,
      immediately after the 1st stress, immediately after the 3rd stress and the day
      after the 3rd stress. The results of this experiment were as follows: (1) The
      total leukocyte counts in the blood of the rats after the 1st trial was
      significantly higher than that before the 1st trial. (2) The percentage of
      lymphocytes in the blood after the 1st trial was significantly lower than that
      before the 1st trial, whereas that of neutrophils was significantly higher. (3)
      Correlations between phagocytic activity and superoxide production of neutrophils
      by histochemical NBT reduction assay showed significantly a positive correlation
      before the 1st trial. However, no significant correlations were observed in
      immediately after the 1st trial and the 3rd trial. The day after the 3rd trial, a
      positive correlation was observed again. These correlations showed that an
      unsuitable state of the neutrophil function was induced by the immobilization
      stress. (4) Serum biochemical profiles were affected by the immobilization
      stress. Also, GOT, GPT, LDH, CK and UA were increased after the 1st trial,
      whereas, TG, TP, ALB and ALP were decreased after the 1st trial. T-CHO was
      increased only immediately after the 3rd stress. These results suggest that
      immobilization stress affected blood cells and serum components, and then the
      host defense and physiological functions were damaged respectively.

PMID- 9528264
TI  - [Estimation of the future numbers of patients with diabetes mellitus in Japan
      based on the results of national patient surveys].
AB  - The projected numbers of patients with diabetes mellitus (ICD 9th; 250) 15 years
      from now were estimated. First, the numbers of patients with the disease in 1984,
      1987, 1990, and 1993 were calculated by age and sex using data from the National
      Patient Surveys conducted by the Ministry of Health and Welfare. Then, population
      prevalence for calendar years 1996, 1999, 2002, 2005, and 2008 were estimated
      based on the past data using linear regression models. Finally, the total numbers
      of patients were calculated from the estimated prevalence multiplied by the
      estimated population figure of the national government. The prevalence and the
      numbers of patients are estimated to increase, and the numbers will be 1.7
      million among males and 1.5 million among females in 2008. Besides, because of
      the increases of both the aged population and the disease prevalence, the
      proportion of patients aged 65 years or over will become as large as 40% of total
      male patients and 60% of females.

PMID- 9528265
TI  - [Mercury sensitization induced by environmental exposure].
AB  - We investigated mercury sensitization in relation to urinary and hair mercury
      concentrations. Patch tests were performed on 215 medical students and these
      tests demonstrated that 28 students were mercury-sensitized (13.0%). Life-styles
      were studied by questionnaire in 26 of the mercury sensitized students and 46 of
      the non-sensitized subjects. Urinary mercury concentrations were measured in 25
      sensitized and 46 non-sensitized and hair mercury concentrations were measured in
      19 sensitized and 22 non-sensitized subjects. The eating of fish was not
      significantly associated with mercury sensitization (one-tailed t-test). The
      number of teeth treated with metals in the sensitized group was significantly
      higher than in the control group (6.8 +/- 4.3 in sensitized vs. 4.8 +/- 4.1 in
      non-sensitized, one-tailed t-test. p < 0.05). The usage of mercurochrome was not
      significantly associated with mercury sensitization (chi-squared test). Urinary
      mercury concentrations were not significantly higher in sensitized subjects. Hair
      mercury concentrations were significantly higher in sensitized subjects (1.98 +/-
      0.91 micrograms/g in sensitized vs. 1.23 +/- 0.53 in non-sensitized, one-tailed t
      test p < 0.05). These results suggest that mercury sensitization is associated
      with increased hair mercury concentrations but not with urinary mercury
      concentrations. In this study it is confirmed that dental amalgam for treating
      teeth may be an important factor relating to mercury sensitization.

PMID- 9528266
TI  - [A study of the effects of physical load on umpires during the national high
      school baseball games--the effects of physical load on umpires at the Koshien
      stadium in a summer-heat environment].
AB  - This study attempted to measure the physical load on national high school
      baseball umpires during games played at Koshien stadium under extremely hot and
      humid conditions in the summer. Thirty-one umpires participated in this study.
      Thirteen of them were evaluated twice while eighteen were evaluated only once.
      The factors used to determine physical load were the following: body weight, oral
      temperature, blood pressure, heart rate, and serum biochemical elements. These
      were measured before and after the games. Heart rate was measured at one-minute
      intervals. The results were as follows. 1) All the games were played under
      conditions of extremely high temperatures--32.1 degrees celsius dry-bulb, 27.0
      degrees celsius wet-bulb, 36.8 degrees celsius black-globe, 29.5 degrees--WBGT
      which are likely to cause heat-related illnesses. 2) The physical load of
      baseball umpires during the game showed a 1.69 percent decrease in average body
      weight due to perspiration, a 0.43 degrees C increase in oral temperature and an
      increase in heart rate. An examination of the serum biochemical elements showed
      that muscle deviation enzymes changed due to muscular activity and blood
      condensed due to perspiration. The physical load levels of baseball umpires were
      influenced by extreme heat and physical activity during the game. 3) There were
      no observable differences in either the amount of physical activity or the
      extreme heat environment among the umpires of different field positions. But the
      chief umpire's physical load showed a greater decrease in body weight, more blood
      condensation due to perspiration as a result of the heavier equipment he wore,
      more muscular activity and higher energy consumption than his counterparts on the
      bases. 4) The umpire's heart rates were higher during games than before games.
      The moment they were on the playing field. Their heart rates rose to an average
      of 134. It remained above 115 for about two hours, apparently caused by physical
      activity and heart load.

PMID- 9528267
TI  - [Clinical application of A-W glass ceramic (dence and porous A-W glass ceramic)].

PMID- 9528268
TI  - Suppression of hepatic portal blood flow caused by carbon dioxide
      pneumoperitoneum can be restored after dopamine administration in pigs.
AB  - Portal venous blood flow (PVF), hepatic arterial blood flow (HAF) and systemic
      arterial pressure (SAP) were examined after dopamine (DA) injection into the
      jugular vein under carbon dioxide pneumoperitoneum in pigs. When intraabdominal
      pressure (IAP) was increased by 12 mmHg, PVF and HAF were reduced, but SAP was
      unchanged. When IAP was kept at 12 mmHg, the injection of DA at 10
      micrograms/kg/min for 2 min produced an increase in PVF without causing any
      change in HAF or SAP. The response in PVF was dose-dependent. When IAP was
      increased to 16 mmHg, PVF response was diminished, and no change in HAF or SAP
      was seen at the same dose of DA. These observations suggest that DA is effective
      in increasing PVF under enhanced IAP conditions, but such circulatory improvement
      due to the agent would be prominent when IAP is below 12 mmHg.

PMID- 9528270
TI  - CT findings of extravasation of contrast medium from a ruptured aneurysm during
      cerebral angiography--a case report and six others from the literature.
AB  - We present a case of ruptured aneurysm in which extravasation of contrast medium
      was suspected during cerebral angiography and confirmed by computed tomography.
      In cases of ruptured aneurysm, post-angiographic computed tomography before
      operation (measurement of the Hounsfield unit numbers and grading by them) is
      necessary for establishing the diagnosis of extravasation of contrast medium and
      for grasping its degree and extent.

PMID- 9528269
TI  - Clinical evaluation of the efficacy of an antithrombin agent "Argatroban"
      combined with exercise therapy on increase of the skeletal muscle blood flow.
AB  - Argatroban has selective antithrombin activity and widely used for treatment of
      ASO. In this study we investigated vasodilating activity of Argatroban besides
      antithrombin activity in ASO patients. Three patients who have undergone F-P
      bypasses previously which were all occluded received 10 mg or 20 mg of Argatroban
      per day intravenously for 4 weeks. Skin temperature were measured before and
      after administration of Argatroban at the point of 1, 2, 4 weeks which increased
      2.3-6.0 degrees C after administration of Argatroban. Subjective symptoms were
      also improved and these patients became to be able to walk 1.5-3.3 km. These
      patients were also given PGE, intravenously, however, temperature increase was
      less than 1.1 degrees C. These results showed that Argatroban has not only
      antithrombin activity but also significant vasodilating activity resulting in
      increase of skeletal muscle blood flow.

PMID- 9528271
TI  - [Auxiliary partial orthotopic living related liver transplantation].

PMID- 9528272
TI  - A study of breast cancer in young women: prognosis and prognostic factors.

PMID- 9528273
TI  - Hepatolithiasis in Japan.

PMID- 9528274
TI  - [Gender differences in lifestyles of the middle-aged and the elderly--a study in
      Satomi village, Ibaraki, Japan].
AB  - The purpose of this study was to examine the gender differences in the total
      lifestyles of the middle-aged and the elderly. A self-administered questionnaire
      was employed to assess the lifestyles of inhabitants aged 40 years and over. Only
      400 middle-aged and elderly who lived in Satomi village, Ibaraki Prefecture were
      randomly sampled for this study. Though the questionnaires contained 99 items
      such as nutrition, exercise, cigarette use, alcohol use, rest; we used only 84
      items in this study. Satomi village is a rural area with a population size of
      approximately 4,500 and an aging rate of 25.9%. Questionnaires were sent to the
      subjects by mail. The response proportion was 90%, and the valid response
      proportion was 85.3%. Subjects included 155 men and 186 women. The average age of
      all subjects was 61.5 +/- 12.0 years old: males; 60.8 +/- 11.5 years old,
      females; 62.1 +/- 12.4 years old. Gender differences were assessed for selected
      items with the chi 2 test. Women tended to have significantly better health
      habits on items such as nutrition, alcohol intake, and cigarette use (p < 0.05).
      Factor analysis with varimax rotation was used to separate the items. Three
      factors that had eigenvalues substantially > 1.0 were extracted and explained
      49.7% of the total variance. Factor 1 reflects health promotional activities;
      Factor 2 denotes health preventive activities; Factor 3 reflects the avoidance of
      health risk. Though gender differences were not observed for Factor 1 (p =
      0.8647), they were seen for Factor 2 (p = 0.0003) and Factor 3 (p = 0.0001) with
      the Wilcoxon rank sum test. Wilks'lambda test was utilized as likelihood ratio
      test mean vectors of Factor 1, Factor 2, and Factor 3 (p = 0.0001). The results
      of the Wilks'lambda test indicated significant gender differences. Our findings
      suggest significant gender differences in the total lifestyles, but not in the
      individual lifestyle habits.

PMID- 9528275
TI  - [Self-efficacy and related factors related in Parkinson's disease patients].
AB  - This study was designed to assess self-efficacy and the factors leading to higher
      self-efficacy in Parkinson's disease patients, as measured by General Self
      Efficacy Scale (GSES). Questionnaires were mailed to patients with Parkinson's
      disease in Tokyo. This study surveyed 73 male and 70 female patients.
      Approximately 66.5% of the patients fell into the low self-efficacy group. Data
      was divided into 3 groups (high, moderate and low) and evaluated statistically.
      Approximately 66.5% of the patients fell into the low self-efficacy group.
      Patients in the high self-efficacy group exhibited the following features: Males:
      1) The male patients in the high self-efficacy group tended to belong to more
      groups and had less trouble than any other groups in coping with their daily
      lives; 2) they generally had people to turn to for mental support outside their
      families, and for their daily life inside or outside their families; 3) they also
      felt confident that they had sufficient understanding of better life styles and
      how to exercise. Females: 1) The female patients in the high self-efficacy group
      tended to go out more often than any other groups and had places to go where they
      could practice hobbies and exercise; 2) they generally had people outside their
      families to turn to for mental support; 3) their subjective symptoms, such as
      freezing and dysarthria, tend to be less acute than in the moderate or low self
      efficacy patients. 4) had les trouble than any other groups in coping with their
      housing accommodations; 5) they also felt confident that they understood how to
      exercise. In order to increase self-efficacy among Parkinson's disease patients,
      this study suggests that support, both social and psychological, and providing
      health education, are important.

PMID- 9528276
TI  - [The care principles of home care based on the cognition of care providers].
AB  - The purpose of this study was to clarify the care principles that are most highly
      valued by various care providers, including public health nurses, home visiting
      nurses, home helpers, and case-workers, by factor-identification-study (KJ
      method), and to consider measures for sharing care principles among these
      sectors. It was found that care principles are composed of three factors: "User
      oriented care", "Good mutual relationship", and "Self-improvement". Also there
      are differences in cognition of these according to occupation, workplace,
      experience, and so on. We should develop strategies for improving the quality of
      user-oriented care, as we understand the differences in cognition of care
      principles, and as we share the experience gained in each working aria.

PMID- 9528277
TI  - [Relationships between resting behavior and health locus of control among
      elementary schoolgirls].
AB  - PURPOSE: To clarify the effects of Internal Health Locus of Control (IHLC) on the
      practice of resting behavior. Resting has recently gained attention because of
      overwork and stressful social situations. We investigated daily preventive health
      behaviors and Health Locus of Control (HLC) in children and their mothers over
      three years from 1991. This paper reports on the relationships between resting
      and IHLC among elementary schoolgirls. METHODS: The subjects of this study in
      1991 were public elementary schoolgirls in their 3rd year (8-9 years old) and
      their mothers. Three years, later in 1994, we investigated the same children and
      their mothers, with 104 girls answering questionnaires in both studies. The
      resting behavior data was obtained from the question "Do you rest or take a nap
      when you are very tired?". We used Parcel & Meyer's Children's HLC Scales for
      children and Horige's Japanese version of Health Locus of Control (JHLC) Scales
      for mothers. Only the data concerning IHLC was extrapolated for this study.
      RESULTS: 1. The data for resting behavior for 1991 in the 3rd grade did not
      coincide with that for 1994 in the 6th grade. On the whole rest was taken more
      frequently in the 3rd grade than in the 6th grade. 2. Perceived health state had
      a significant association with resting behavior. 3. Girls who perceived rest was
      relating directly to their personal health, took a rest more often than those who
      did not perceive a personal application for rest. 4. IHLC data distribution shows
      a marked difference between grades. Scores were significantly higher in the 6th
      grade than in the 3rd grade. This rising tendency of internality seems to be a
      developmental change. 5. IHLC scores of 1991 3rd graders classified their 3rd
      grade behavior patterns. The 3rd grade (1991) "usually taking a rest" group
      scored significantly higher than the other groups. 1991 IHLC scores classified
      their 1994 6th grade behavior patterns. The 6th grade (1994) "usually taking a
      rest" group also scored significantly higher than the other groups. 6. The data
      for resting behavior of the girls did not coincide with that of their mothers.
      There were no correlations between the girls's IHLC scores and their mothers's
      IHLC scores. CONCLUSION: This study revealed some significant relationships
      between resting behaviors and IHLC scores among the schoolgirls. It seems that
      girls who had high IHLC tendency in the 3rd grade were growing up with this
      tendency. Perhaps in the interest of self-care, they elected to rest to keep
      healthy when they were tired.

PMID- 9528278
TI  - [Correlates and prognosis in relation to intellectual dysfunction in a community
      residing elderly population].
AB  - To estimate the risk factors for intellectual dysfunction and examine its
      prognosis in a community-residing (non-institutionalized) elderly population, a
      randomly selected sample of 1,473 elderly people aged 65 years and over living in
      S city, Osaka Prefecture, was studied in October 1992, and data were obtained
      from 1,383, a response rate of 93.9%. A cohort of 1,383 was followed for 42
      months and follow-up was completed for 1,300 (94.0%). The main results were as
      follows: 1) The prevalence of intellectual dysfunction did not differ
      significantly between sexes, and there was an increasing prevalence of
      intellectual dysfunction with age in both sexes. The prevalence of severe
      intellectual dysfunction was found to increase highly at age 85 and over. 2) By
      univariate analysis, odds ratios for age older than 75 years, low Activities of
      Daily Living (ADL), urinary and fecal incontinence, and no participation in
      social activities were significantly higher than 1 in any level of mild,
      moderate, and severe intellectual dysfunction. In the multivariate analysis using
      logistic regression, age older than 75 years and urinary and fecal incontinence
      showed significant higher odds ratios than 1 for severe intellectual dysfunction,
      and low ADL and treatment for hypertension also showed significant higher odds
      ratios than 1 for moderate intellectual dysfunction. 3) From analysis using the
      Kaplan-Meier method, the cumulative survival rates decreased with a decline in
      intellectual functioning in both age groups of 65-74 and 75 years and older. 4)
      Application of the Cox proportional hazards model resulted in adjusted hazard
      ratio for severe intellectual dysfunction of 1.79 (95% confidence interval, 1.02
      3.12), controlling for other factors such as sex, age, general health status,
      incontinence and social activities.

PMID- 9528280
TI  - [Mental health surveys of old people, using self-rating depression scale(SDS)
      comparison between ones in hospital with ones at home].

PMID- 9528279
TI  - [An interview survey on the effectiveness of home dental care for home bound
      patients in Niigata prefecture].

PMID- 9528281
TI  - [Change of the number of heart disease deaths according to the revision of the
      death certificates in Oita city].

PMID- 9528282
TI  - [Time factors--next challenge in cardiology].

PMID- 9528283
TI  - [Radiofrequency ablation of arrhythmia--considerable progress].
AB  - Today, the majority of paroxysmal tachycardias can be cured by radiofrequency
      catheter ablation, obviating the need to use anti-arrhythmia drugs or open heart
      surgery. The history, the indications, the results and complications of current
      practice are reviewed.

PMID- 9528284
TI  - [Positron emission tomography of the heart. From research to clinical practice].
AB  - Positron emission tomography (PET) is used as diagnostic and in identifying
      patients with reversible ischaemic dysfunction, and for non-invasive
      investigation of myocardial perfusion. The development of new positron-emitting
      tracers and user-friendly techniques suggests that the method is suitable for
      much wider usage, and usage over a large range of applications.

PMID- 9528286
TI  - [Scandinavian cooperation in cardiovascular epidemiology].
AB  - The Nordic Network in Preventive Cardiology (NNPC), a new forum intended to
      promote collaboration between the Nordic countries in the epidemiology and
      prevention of cardiovascular disease, was founded in November 1996 at a meeting
      of 30 representatives from nine Nordic cardiovascular centres. The plans include
      among other things the creation of a data base of population and intervention
      studies, to organize seminars and workshops, to standardize measuring techniques,
      questionnaires and analysing methods. The NNPC has established contract with the
      European Society of Cardiology and various centres in the Nordic countries.

PMID- 9528285
TI  - [Biological aging and apoptosis--mechanism in cardiovascular disease?].
AB  - Smoking, lipid disorders, hypertension and diabetes are well known risk factors
      for cardiovascular disease. Many individuals are characterised by a genetically
      determined predisposition and moreover, psychosocial factors and an inappropriate
      life style may exert adverse effects on biological variables. Evidence exists
      which suggests that in such cases various ageing processes may be accelerated.
      Studies of apoptosis regulation can yield improved understanding of such
      phenomena as atherosclerotic plaque rupture and such structural cardiovascular
      changes as left ventricular hypertrophy. A possible clinical result of such
      events may be manifest myocardial infarction, followed by heart failure and a
      predisposition to arrhythmia. The recent identification of apopain, a proteolytic
      enzyme associated with apoptosis, may eventually enable drugs to be developed for
      the regulation of apoptosis.

PMID- 9528287
TI  - [Does mad cow disease cause the new variant of Creutzfeldt-Jakob disease?].

PMID- 9528288
TI  - [General practitioner's handbook and database will be international].

PMID- 9528289
TI  - [The role and importance of CT-guided stereotaxic brain biopsy in neurosurgery.
      Experiences with 523 cases].
AB  - Between 1989 and 1996, 523 stereotactic biopsies of different intracranial
      lesions were performed at our institution. In 96.3% of the cases accurate
      histological diagnosis was made. In 59 cases the drainage of the abscess or cyst
      was carried out. In 48 cases the lesion was axial, in 27 parasellar, 7 pineal and
      37 infratentorial. In the rest of the cases the lesion was in the supratentorial
      hemispheres. Transient neurological deficits were observed in 3.4% of the cases
      and craniotomy with haematoma evacuation had to be carried out in one case
      following the biopsy. There was no mortality associated with the interventions in
      our material. Our experience supports that CT guided biopsy is a safe and
      efficient method for obtaining histological diagnosis in different intracranial
      lesions and showed to be very useful in planning te appropriate treatment for
      each patient.

PMID- 9528290
TI  - [Experience with gestodene-containing hormonal contraceptive].
AB  - An oral contraceptive containing gestodene (Minulet) was examined in
      collaborating with the Richter-Wyeth Pharmaceutical Factory. The authors present
      their experiences of monitoring of 591 cycles of a hundred women between 18 and
      35 years of age. There were no pregnancy and severe side effects during that
      period. Irregular bleeding occurred in 17.5% of women in the beginning of the
      treatment, however it gradually decreased and ceased by the fifth cycle. Both the
      length and the quantity of the withdrawal bleeding decreased by the end of the
      sixth cycle. During the observation there was no amenorrhoea and the
      dysmenorrhoea presented a decreasing tendency, expressing in per cent of the
      cycles. Their own data support, that the oral contraceptives containing gestodene
      meet requirements of today's medical science, and beyond the low hormone content
      they also fulfil the next demands: reliable contraceptive effect, efficacy,
      excellent cycle control, good tolerability and limited side effects.

PMID- 9528291
TI  - [Indirect methods in the genetic diagnosis of hemophilia A].
AB  - In haemophilia A (HA), besides the direct detection of the most common mutation
      of the factor VIII gene (the gene inversion), it was necessary to establish
      indirect methods which are suitable to reveal the pattern of inheritance of the
      genes examined, regardless of the mutations they carry. This task can be achieved
      by the analysis of DNA polymorphisms located within and in the near proximity of
      the factor VIII gene. For diagnostic purposes we used an RFLP and two
      microsatellite polymorphisms. The aim of our program is to provide carrier and
      also prenatal diagnostics for affected families. So far we completed the analyses
      of 15 HA patients and 68 of their family members, and we gave prenatal diagnoses
      in 3 cases. According to the information content of the polymorphisms used, we
      expect to be able to provide DNA diagnoses to 95% of the Hungarian HA families
      requesting the test.

PMID- 9528292
TI  - [Incidence and mortality of extrauterine pregnancy in Hungary (1931-1995)].
AB  - The authors report on the changing incidence of and maternal mortality from
      ectopic pregnancies in Hungary between 1931 and 1995. Data of reported
      pregnancies were obtained from the National Institute of Statistics and the
      Hungarian College of Obstetricians and Gynecologists. Incidence of ectopic
      pregnancy was calculated as rates per 1000 live births and per 1000 reported
      pregnancies including live births, legally induced abortions, miscarriages, and
      ectopic pregnancies. Ectopic pregnancy-associated maternal mortality was examined
      in terms of case fatality rate and also as a proportion to the total number of
      pregnancy-associated maternal deaths. From 1931, when national surveillance for
      pregnancy begun in Hungary, to 1995, the rate per 1000 reported live births
      tripled from 3.4 to 11.9. Similarly, the rate of ectopic pregnancies per 1000
      reported pregnancies increased by 190% from 3.7 to 6.4. In the last decade of the
      period studied, its proportion in the annual number of fetal deaths increased to
      8.0%. Ectopic pregnancy-associated maternal deaths decreased sharply from 1931
      through the late 1980's. In the last decade, its average value was 16 per 10.000
      reported ectopic pregnancies. However, case fatality rate of ectopic pregnancy is
      still highest compared to any of the other obstetric events including induced and
      spontaneous abortions, and deliveries. Over the last decade, maternal deaths
      resulting from ectopic gestation represented 8.7% of the total maternal mortality
      rate. Given the increasing incidence of ectopic pregnancy together with a
      substantial proportion in pregnancy-related maternal mortality, study of
      etiology, and appropriate preventive measures are urgently needed.

PMID- 9528293
TI  - [Biometric concepts and function theory].
AB  - r shows the basic concepts of function theory, which ones are necessary in
      biometrical works. The concept of the function, the different mapping methods and
      some often used function types are presented.

PMID- 9528294
TI  - [Prevalence of viral markers for hepatitis B, C and human immunodeficiency virus
      in volunteer blood donors in Northeast Mexico].
AB  - OBJECTIVE: To ascertain the prevalence of Hepatitis-B, Hepatitis-C and Human
      Immunodeficiency-Virus (HIV) markers among altruistic blood donors. PLACE: Blood
      bank of a third-level-hospital belonging to the Instituto Mexicano del Seguro
      Social (IMSS) system. SUBJECTS: Written records of the blood bank were reviewed,
      including charts of all risk free potential altruistic donors who between 1994
      and 1995 had determination of: Hepatitis-B surface antigen (HBsAg), Hepatitis-B
      core antibodies (anti-HBc), Hepatitis-C antibodies (anti-HCV) and Human
      Immunodeficiency-Virus (HIV). RESULTS: Of 78,566 potential blood donors studied
      2,187 (2.8%) reacted to one or more markers, 2% were anti-HBc positive, 0.47%
      anti-HCV positive, 0.16% HBsAg positive and 0.12% anti-HIV positive. CONCLUSIONS:
      Prevalence of virus markers examined is equal or lower than reported worldwide as
      well as in our country in the 90; this reflects improved education and selection
      of potential donors and encourages the use of subsequent donation.

PMID- 9528295
TI  - [Comparative study of laparoscopic appendectomy vs open appendectomy].
AB  - Laparoscopy reduces the risk of performing unnecessary appendectomies and offers
      the advantages of minimal invasive surgery when appendectomy is needed. We report
      our experience comparing open (Group A) with laparoscopic (Group B) appendectomy.
      PATIENTS AND METHODS: There were 20 patients in each group. Age, sex, signs,
      symptoms, evolution, laboratory, stage of disease, drains, duration of surgery,
      antibiotics, oral intake restart, postoperative pain at 24, 48 and 72 hours,
      complications, hospital stay, return to normal activities and cosmesis were
      reviewed. Statistical differences were determined using Student's t test (two
      tailed) or chi-square with Yates correction. Surgical technique is described.
      RESULTS: In both groups most variables were similar (p = ns). Group B presented
      earlier oral intake restart (p < 0.001), and less postoperative pain at 24 (p <
      0.001), 48 (p < 0.01) and 72 hours (p < 0.001). Hospitalization stay was shorter
      (p < 0.001) and return to normal activities was earlier (p < 0.001) in group B.
      Better cosmetical appearance was observed in Group B (16 vs. 0 "excellent" -p <
      0.001). CONCLUSIONS: Laparoscopic approach may reduce unnecessary appendectomies
      and it allows to perform appendectomy in a safe and effective way. In this study,
      laparoscopic was better than open appendectomy regarding early restart of oral
      intake, less postoperative pain, shorter hospitalization stay, earlier return to
      normal activities and better cosmetic appearance.

PMID- 9528296
TI  - [Surgical treatment of colonic volvulus. 10-year experience at the Instituto
      Nacional de la Nutricion Salvador Zubiran].
AB  - OBJECTIVES: To analyze morbidity-mortality and results of surgical treatment for
      colonic volvulus. METHODS: Retrospective review of 33 patients who underwent
      surgical treatment for colonic volvulus from 1986 through 1996. RESULTS: Mean age
      was 62 +/- 20 years (SD) with predominance of female sex (2:1). There were 25
      cases of sigmoid volvulus (76%), 7 in the cecum (21%) and 1 in the transverse
      colon (3%). Colonic necrosis and/or perforation were most frequently seen in the
      right and transverse colon (50%) than in the sigmoid (4%) (P < 0.002). Operative
      morbidity was 45% with mortality of 21%. Age was the only variable statistically
      significant for operative morbidity (52 +/- 23 years in patients without
      morbidity vs 71 +/- 17 years in patients with morbidity, P = 0.02). Surgical
      procedures for sigmoid volvulus were resection in 13 and fixation in 12.
      Recurrence after fixation was 38% to 12 months and 69% to 24 months (Kaplan
      Meier), with associated mortality of 50%. There was no recurrence after
      resections. Treatment for cecal volvulus was cecopexy in 4 cases, with one
      recurrence; and right hemicolectomy without recurrence. CONCLUSIONS: The results
      should encourage resective procedures in sigmoid volvulus because the risk of
      recurrence after fixation is high and the morbidity-mortality is similar. Elderly
      patients are more susceptible to complications.

PMID- 9528297
TI  - [Diaphragmatic hernia caused by penetrating injury: emergency laparoscopic
      reconstruction].
AB  - OBJECTIVE: To inform a patient with penetrating thoracic trauma and diaphragm
      injury that produced stomach herniation, being reduced the hernia and repaired
      the injury by laparoscopy though abdominal route with excellent result. REPORT:
      17-years-old male, hemodynamically stable with penetrating injury in the fifth
      left intercostal space, at the level of the middle auxiliary line, pneumothorax
      and left diaphragmatic hernia. Treatment. A pleurostomy tube was inserted. By
      laparoscopy 600 mL of free blood in abdominal cavity were aspired, the stomach
      hernia was reduced and the diaphragmatic repair was performed with nylon 3-0
      running suture. The evolution was excellent, being integrated to his work at the
      twentieth postoperative day. COMMENTARY: Our case supports that laparoscopic
      surgery is at therapeutic alternative in select cases of trauma.

PMID- 9528298
TI  - [Rapunzel's syndrome (trichobezoar)].
AB  - The Rapunzel syndrome is uncommon, only 6 cases have been previously reported.
      Its characteristics are: 1) the body of a trichobezoar located in the stomach,
      and its tail in the small bowel and/or in the right colon, 2) small or large
      bowel obstruction, 3) occurring in psychiatric patients and, 4) trichophagia. We
      have added an additional patient, who was submitted to our hospital with
      diagnosis of abdominal mass, who, during his work-up was found with the above
      mentioned characteristics. The patient underwent a exploratory celiotomy,
      gastrotomy, and the trichobezoar was removed. The pathogenesis and current
      treatment are reviewed.

PMID- 9528300
TI  - [Clinical images in gastroenterology. Polycystic disease of the adult].

PMID- 9528299
TI  - [Hirschsprung's disease: neurocristopathy of migration and cell differentiation].
AB  - Hirschsprung disease or aganglionosis coli, is a predominantly pediatric
      condition, in which there is an innervation defect of the colon, manifested by
      chronic intermittent constipation alternating with explosive evacuations. The
      involved colonic segment is unable to relax and acts as an area of obstruction,
      which causes the proximal segment to dilate enormously. The diagnosis requires
      participation from several specialties, including pediatric surgery,
      gastroenterology, radiology and anatomic pathology. In recent years, significant
      progress in relevant knowledge of this area has been obtained, in particular
      about defective migration of the neural crest-derived colonic ganglion cell
      precursors, as well as the genetic aspects of the disease. This article reviews
      the diagnostic anatomic pathology and the most relevant points about the biology
      of Hirschsprung disease.

PMID- 9528301
TI  - [Clinical images in gastroenterology. Phytotrichobezoar].

PMID- 9528302
TI  - [Clinical images in gastroenterology. Adenomatous polyp of the cecal appendix].

PMID- 9528303
TI  - Frequency of motor neuron diseases in a Mexico City referral center.
AB  - OBJECTIVE: To analyze the incidence and clinical characteristics of MND (Motor
      Neuron Diseases) in a Mexican institution. MATERIAL AND METHODS: It was a
      retrospective study, of 274 definitive MND patients seen in a neurological
      reference hospital of Mexico City during the period of 1965-1995 (248 as
      Amyotrophic Lateral Sclerosis, 15 as Progressive Bulbar Palsy, 8 as Primary
      Lateral Sclerosis and 3 as Progressive Spinal Atrophy). RESULTS: The frequency of
      MND increased gradually in our institution in the 31 years revised. The mean age
      of onset in our series was approximately 48 years in contrast to a higher age
      found in other series. The clinical features are similar to those found
      elsewhere. CONCLUSIONS: Our study showed that the frequency of MND is increasing
      in Mexico in a similar fashion to that observed in the rest of the world. This
      makes conceivable that the incidence of MND in Mexico may also resemble the
      figures reported worldwide. Prospective population studies are required to
      establish the incidence of MND in Mexico.

PMID- 9528305
TI  - [Cellular immunophenotypes in 97 adults with acute leukemia].
AB  - OBJECTIVE: To analyze hematopoietic cell surface antigen reactivity in acute
      leukemia (AL) by flow cytometry and identify acute mixed-lineage leukemias (AMLL)
      employing the most widely accepted criteria. MATERIAL AND METHODS: Ninety seven
      patients with de novo AL were studied. Cell surface antigens were investigated
      with monoclonal antibodies directed to: B lymphoid (CD10, CD19, CD20, CD21,
      CD22); T lymphoid (CD2, CD3, CD5, CD7); and myeloid (CD13, CD14, CD15, CD33,
      CD41) cell lineages. Maturation cell-associated antigens (CD34, HLA-DR and TdT)
      were also studied. RESULTS: Twelve patients unclassified by cytomorphology could
      be classified by immunophenotype. Using cytomorphologic, cytochemical and
      immunophenotypic data, 54 cases corresponded to acute lymphoblastic leukemia
      (ALL) and 43 were acute myeloblastic leukemia (AML). In All there were 63% B
      lineage, 15% T, 7% T/B, 6% undifferentiated and 9% mixed-lineage (coexpression of
      two or more myeloid-associated antigens). In AML, myeloid immunophenotype was
      observed in 86% undifferentiated in 2%, and mixed-lineage in 12% (coexpression of
      two or more lymphoid-associated antigens). In addition, 26% of ALL cases and 12%
      of AML cases expressed a single myeloid and lymphoid antigen respectively. The
      most common aberrant antigens in ALL and AML were CD13 and CD7 respectively. The
      highest frequency of CD34 antigen expression (90%) was detected in patients with
      AMLL. CONCLUSIONS: Flow cytometric immunophenotypic analysis allowed to: a)
      establish diagnosis in cytomorphologically unclassified cases; b) identify AMLL
      with a frequency similar to that reported in other series; and c) confirm the
      heterogeneity of AL.

PMID- 9528304
TI  - Recombinant human granulocyte-macrophage colony-stimulating factor as treatment
      for chronic leg ulcers.
AB  - OBJECTIVE: To evaluate the safety and effectiveness of a single subcutaneous
      perilesional administration of 300 micrograms of recombinant human granulocyte
      macrophage colony stimulating factor (rHGM-CSF) for the treatment of chronic leg
      ulcers. DESIGN: Prospective, descriptive evaluation in an outpatient group.
      SETTING: The Centro Medico Nacional 20 de Noviembre, ISSSTE, Mexico City.
      PATIENTS: 10 patients with chronic leg ulcers. MEASUREMENTS: Ulcer diameter and
      side effects. RESULTS: After 4 weeks observation, 8 of the 10 ulcers had healed;
      the other two had a mean diameter decrease of 21%. The only side effect was found
      in a 58 year old female who complained of moderate perilesional pain two days
      after having received treatment: it was successfully treated with paracetamol.
      CONCLUSION: We believe that a single perilesional subcutaneous administration of
      rhGM-CSF is safe and effective for the treatment of chronic leg ulcers.

PMID- 9528307
TI  - [Ability of pediatric residents to read critically research papers].
AB  - OBJECTIVE: To explore ability to read clinical research papers by pediatric
      residents at different stages of their training. SETTING: Four hospitals of the
      Mexican Social Security System located in Mexico City. MATERIAL AND METHODS: An
      instrument to evaluate the ability to read critically pediatric research papers
      was developed and validated by four experts. It contained four abstracts
      generated from research articles and was integrated by 30 interpretation items,
      30 judgment items and 30 alternative proposals items, to be answered by the true
      false- don't know system. RESULTS: Sixty seven residents participated (21 first
      year, 20 second year and 26 third year level). There were no significant
      differences in interpretation, judgment and overall scores between groups. There
      was a significant degree of agreement in the ordinality of the residents for the
      scores in interpretation, judgment and proposals (Kendall W = 0.55, p < 0.001).
      CONCLUSIONS: We conclude that the residents were not influenced by the training
      received during their residence in regard to their ability for critical reading
      of clinical research papers.

PMID- 9528306
TI  - [Experience with 22 bone marrow donors].
AB  - We describe our experience of the Instituto Nacional de Cancerologia in Mexico
      City in the management of 22 healthy donors of the allogeneic bone marrow
      transplantation program. Twenty three bone marrow products were harvested from
      the 22 healthy donors (7 male, 15 female) with a median age of 26 (range 16 to
      47). All were seronegative for HIV, HBV and HCV. The volume harvested ranged from
      750 to 1500 mL. The postoperative hemoglobin dropped more than 3 g/dL in 14
      donors but only seven required the transfusion of autologous blood collected
      before the procedure. All donors received a standard analgesic regimen with
      meperidene, dextropropoxiphene and ketoprofen for 24 hours after the harvest.
      Only two instances of procedure complications were recorded (9%) and were
      successfully resolved. Currently all donors are alive and in good health with a
      median follow up of two years. We conclude that bone marrow donation is a safe
      procedure with some predictable complications, the most common, anemia, easily
      corrected with autologous blood transfusion.

PMID- 9528308
TI  - [Prevalence of viral antibodies and syphilis serology in blood donors from a
      hospital].
AB  - OBJECTIVE: To establish the prevalence of viral antibodies and luetic reagins in
      blood donors in a Mexican hospital. SETTING: A third level general hospital for
      government employees located in the city of Morelia, State of Michoacan, Mexico.
      MATERIAL AND METHODS: Blood samples were collected from 10,077 healthy volunteer
      donors in a seven year period (01/01/90 to 12/31/96). Serologic tests were
      performed for HIV antibodies (anti-HIV), HBsAg and RPR. Anti-HCV were tested in
      7,256 samples collected from 07/01/92 to 12/31/96. RESULTS: Anti-HIV was found in
      19 donors (0.18%), HBsAg in 34 (0.33%), RPR in 12 (0.11%) and anti-HCV in 22
      (0.30%). These prevalence rates are in agreement with reports from other Mexican
      blood banks.

PMID- 9528309
TI  - [A psychoanalytic approach to the ethics of the physician-patient relationship].
AB  - A brief review of some ethical issues related to the advancement of science and
      technology is presented. The principles currently considered priorities for a
      healthy relation between patient and physician are discussed, including autonomy,
      intimacy and respect. In addition, due to the linkage between psychoanalysis and
      medicine, some elements that determine the ethics of psychoanalysis-such as
      transference-are analyzed in order to consider their vinculations with the
      physician-patient relationship. Important corollaries emerge, i.e. the physician
      must not forget that he deals with a person, that illnesses have particular
      meanings to patients who also have particular needs, questions and wishes of his
      or her own.

PMID- 9528310
TI  - [Survey of physicians' attitudes to terminal patients].
AB  - OBJECTIVE: To explore the opinion of physicians about euthanasia and the
      treatment of dying patients. DESIGN: A comparative survey. MATERIAL AND METHODS:
      We interviewed 38 family physicians (FP), 38 specialty physicians (SP) and 38
      medical students (MS). The survey had 30 items, five of them about experience
      with terminal patients which were not used for the students. ANALYSIS:
      Descriptive statistics and chi 2 or Fisher test to compare proportions between
      groups. RESULTS: One hundred and two (89%) of the interviewed had a correct
      concept of euthanasia; 105 (92%) thought that life is holy and untouchable; 29
      (25%) agreed there are persons more valuable than others, and four (4%) consider
      that some should die in certain situations. In relation to patients with brain
      death, 79 (69%) believed they should not receive futile treatment, but 42 (37%)
      said they should be attended until cardiac arrest occurred. All agreed with the
      need of the patients to receive comfort and peace, but only 49/76 (64%) of the
      physicians and 28 (74%) of the students were in favor of sending dying patients
      to their home. Nine FP (23%) and 14 SP (36%) stated that in many occasions they
      lacked elements to solve ethical dilemmas. Thirty six (32%) agreed with the use
      of passive euthanasia and 21 (18%) with active euthanasia; the latter was more
      frequent among students. Nine FP (24%) and 13 SP (34%) said they had exceeded
      therapy sometimes and 23 (61%) of the FP and 19 (50%) of the SP considered they
      had stopped treatment too early in some cases. We found no differences in regard
      to euthanasia between physicians and students (chi 2 = 0.32, p = 0.71) nor
      between the physicians with frequent vs occasional contact with terminal patients
      (Fisher = 0.13). CONCLUSIONS: A third of the physicians agreed with some form of
      euthanasia but this frequency is smaller than that in other countries.

PMID- 9528311
TI  - [Production of fungal antigens from local strains for the immunodiagnosis of
      mycoses in Mexico].
AB  - Fungal antigens with good reactivity and specificity are essential for the
      immunodiagnosis of systemic mycoses. We give here data on crude and purified
      antigens of Histoplasma capsulatum, Coccidioidis immitis and Paracoccidioides
      brasiliensis from local strains and which are the more prevalent in Mexico. The
      crude antigens had good reactivity in precipitating and skin testing whereas the
      purified antigens (DPPC: deproteinized polysaccharide protein complex) had a
      higher specificity in more sensitive tests such as ELISA and complement fixation.
      Our efficiency analysis showed that the crude antigens are best for epidemiologic
      studies due to their low cost, easy handling and fast detection. The purified
      ones are suited to establish with more precision the diagnosis of systemic
      mycoses.

PMID- 9528312
TI  - [The Steel factor].
AB  - Mice bearing mutations at either of two loci, dominant White spotting(W) or
      Steel(Sl), exhibit development defects in hematopoietic, melanocytic and germ
      cells. Genetics studies have shown that the SI locus encodes the Steel factor
      (SF), which is the ligand for the tyrosine kinase receptor c-kit, the product of
      the W locus. SF is synthesized in membrane-bound form and can be processed to
      produce a soluble form. Cell-cell interaction is important in the production of
      normal blood cells in vivo and in vitro and in the cellular expansion of leukemic
      cells. We discuss here how SF decreases the requirements in cell interaction for
      blast colony formation in acute myeloblastic leukemia (AML) and the presence of
      membrane-bound SF possibly contributes to the density-dependent growth of the AML
      blasts. We explain that SF is mainly a survival factor for hematopoietic cells,
      of little proliferative effect, which maintains CD34+ hematopoietic cells in an
      undifferentiated state. These properties would potentially allow the maintenance
      of hematopoietic cells in culture for the purpose of marrow purging or gene
      therapy. The activation of the c-kit signal transduction pathway may play a
      significant role in the development of many types of non-hematological
      malignancies by disrupting normal cell-cell interactions and allowing the growth
      of cancer cell populations. In summary, the properties of the SF indicate it has
      a role for survival signals during the process of normal differentiation, AML
      proliferation and in the maintenance of many c-kit+ tumors.

PMID- 9528313
TI  - [Estrogen receptors and the mammary gland].
AB  - For several decades it has been known that steroid hormones, estrogen and
      progesterone, regulate some genes involved in the growth, proliferation and
      differentiation of the mammary-gland in animals and humans. In the last years,
      the presence or absence of the nuclear estrogen receptor has been used by
      clinicians as a marker for tumor malignancy, as a prognostic index or as an
      important parameter for hormonal therapy with anti-estrogenic compounds of some
      hormone-dependent breast cancers. This review shows some advances in the
      knowledge of the structure, function, molecular mechanisms of estrogenic
      activity, and interaction with proteins like protooncogenes and growth factors.
      Also, we refer to the role of the estrogen receptor in the physiophatology of
      breast cancer.

PMID- 9528314
TI  - [Molecular biology in medicine. XII. Analysis of linkage and positional cloning].

PMID- 9528315
TI  - [Fluorides and dental caries prophylaxis: update].

PMID- 9528316
TI  - [Bottle fed children with caries: dental care under general anesthesia].

PMID- 9528317
TI  - [Dental obturations using amalgams: problems and perspectives].

PMID- 9528318
TI  - [Biocompatibility and corrosion of dental alloys].

PMID- 9528319
TI  - [Myoarthropathies of the temporomandibular joint].

PMID- 9528320
TI  - [Infectious endocarditis and antibiotic prophylaxis before dental treatments].

PMID- 9528321
TI  - [Antibiotic therapy in periodontics].

PMID- 9528322
TI  - [Oral candidiasis].

PMID- 9528324
TI  - [Panoramic radiography].

PMID- 9528323
TI  - [Oral lichen planus].

PMID- 9528325
TI  - [Value of oral implantation in endodontics].

PMID- 9528326
TI  - [Oral-dental situation in elderly persons: a public health problem].

PMID- 9528327
TI  - [LAMal: medical-dental allowances are also of concern to physicians].

PMID- 9528328
TI  - [Glaucoma: modern diagnostic and therapeutic approach].
AB  - Primary open angle glaucoma may be a severe ocular disease and may lead to
      blindness if not diagnosed and/or treated in time. The pathogenic mechanism is a
      progressive loss of ganglion cells leading to cupping of the optic nerve head.
      The main risk factor is an elevated intraocular pressure, but optic nerve
      vascular deficiency, neuronal degeneration or genetic factors have to be
      considered as other potential risk factors. The actual diagnostic tools and the
      latest technologies for the medical, laser and surgical treatment are described
      in this paper.

PMID- 9528329
TI  - [Self esteem of adolescents living in Vaud: influence of sex and other
      discriminant factors].

PMID- 9528330
TI  - [Beyond silence--the nurse and the tortured patient].

PMID- 9528331
TI  - [We are all Africans].

PMID- 9528332
TI  - [The recent progress and future prospects of diagnostic DNA testing--experience
      in DNA analysis of serum enzymes].
AB  - Rapid progress in the molecular technology has stimulated attempts to establish
      DNA diagnosis of human diseases. However, advances in technology have led to
      improvements at the research level but not in routine laboratory work because
      only few laboratory tests are covered by medical insurance; the methodologies
      cannot be easily applied to routine work; and the equipment and reagents are
      relatively expensive. This paper provides an overview of recent progress in DNA
      diagnosis and my experience in the DNA diagnostic field. I started working in the
      DNA diagnostic field in January 1988 with research on mutation analysis of
      lactate dehydrogenase subunit deficiency. I worked in Dr. Steven Li's laboratory
      at the National Institutes of Health in North Carolina and discussed with him
      about screening the patient's genomic library instead of using PCR because PCR
      was not adequate for mutation analysis. We successfully completed the mutation
      analysis and I returned to Japan. Thereafter, PCR has been increasingly improved
      and is now applicable to mutation analysis. Currently, amplification is essential
      for many DNA diagnostic technologies. The Human Genome Project has progressed and
      will be finished around 2002. In this process, DNA diagnosis will play an
      important role in the clinical laboratory. Common diseases, such as
      atherosclerosis, diabetes mellitus, hypertension and so on, have also been
      analyzed and the responsible genes will have been identified. Each laboratory
      should have a specialty and characteristic, and should be ready to help and
      assist each other via a network. Network communication is clearly needed by
      laboratories in the future.

PMID- 9528333
TI  - [The blood-born viral infections].
AB  - Recently it has become urgent to establish a risk control system against emerging
      and re-emerging infectious diseases. Many of the emerging and re-emerging
      infectious diseases such as AIDS and viral hepatitis, are induced by viral
      infection via blood. The main causative agents of blood-born viral infection are
      hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus
      (HIV), human T cell leukemia virus type1 (HTLV1), cytomegalovirus (CMV), Epstein
      Barr virus (EBV), and human parvovirus B19. They play the main role in viral
      hospital infections. The risk of them being transmitted by the transfusion of
      screened blood is very low, but it is always possible that infection may occur in
      a window period even after extensive blood screening tests. EBV has been
      recognized as a less serious infectious agent than CMV. Nowadays, biotechnology
      has revealed the broad spectrum of EBV related diseases as chronic active EBV
      infection, compromised lymphoma, gastric carcinoma and other lymphoproliferative
      disorders. There would be some immunocompromised cases needed monitoring after
      transfusion/transplantation as same as CMV infection. Double infection or co
      infection of EBV and CMV are shown to be occasional. The most important tasks for
      risk control of hospital acquired infectious diseases are to prevent second drug
      related AIDS and prion infection due to the transplantation of dura mata derived
      from patients with Creutzfeldt-Jakob disease, and to prevent of needle stick
      infections. Therefore it is necessary to establish a network communication
      between clinical laboratories, institutes and public health organizations for
      more rapid and adequate care with rapid diagnosis by molecular analysis.

PMID- 9528334
TI  - [Clinical chemistry in a fog].
AB  - In medical practice, laboratory tests, especially chemical tests, has been used
      as an important supplementary tool for diagnosis. However, recent "clinical
      chemistry" as a science is stagnant and wandering. Since the clinical importance
      of "clinical chemistry" has been clarified in various fields and deeply permeated
      into daily practice, "clinical chemistry" as a science has come up against a
      brick wall. With such a background, some researchers attempted to find a way in
      the technical field or accuracy management field, i.e., "analytic chemistry". In
      this field, certain results have been obtained, and the analytic accuracy has
      been so improved as to reflect in vivo changes at extremely high accuracy.
      However, this "analytical chemistry" is, so to speak, a field of emergency refuge
      of "clinical chemistry" and not its original state. Many clinical chemical items
      can be analyzed using automatic analyzers, and academic interest is lost due to
      autoanalysis as a black box. In present status, we should develop a new "clinical
      chemistry". The borders between examination areas have become unclear, and
      immunological laboratory techniques have been introduced into clinical chemistry.
      We should estimate new approach using these new techniques and establish their
      clinical significance. In medical practice, not only diagnostic imaging test,
      such as ultrasound imaging CT, MRI for evaluation of organic in vivo changes but
      also clinical test including chemical test for sensitive evaluation of functional
      changes is indispensable. These two examination methods should be combined in
      medical care with "patients" placed in its central position.

PMID- 9528335
TI  - [External quality assessment for clinical microbiology and good laboratory
      management].
AB  - The Tokyo Metropolitan external quality assessment (EQA) program has revealed
      some serious problems in private independent microbiology laboratories in Tokyo
      since 1982. The poor performance in the EQA surveys closely related to poor
      laboratory managements, the type of training, experience of the medical
      technologists or technicians, and supervisory ability of the consultant
      physicians in independent laboratories. Social factors impede the reform of the
      quality assurance of clinical microbiology. Such factors include poor
      infrastructure of continuing education for small private laboratories, closure of
      the central clinical laboratories in the hospitals and outsourcing of laboratory
      tests due to restructuring in response to economic problems, and limited numbers
      of certified clinical pathologists of the Japan Society of Clinical Pathology
      (JSCP). Therefore, the Tokyo Metropolitan EQA Scheme is still confidential and
      its main role is educational. Good two way communication between participants and
      the organizers' clinical pathologists is essential, if the quality of laboratory
      tests is to be improved. The new JSCP edition of the postgraduate training
      requirement in clinical pathology includes "Laboratory Administration and
      Management". Good laboratory management(GLM) is an increasingly important
      component of good laboratory practice. The practice activities of clinical
      pathologists must include general management in addition to exercising there
      specialized knowledge in medicine and technology. Whereas leadership of a good
      clinical pathologist provides the direction of where a good laboratory is going,
      good management provides the steps of how to get there. And I believe quality
      system models from business and industry may provide us with strong guidance to
      build a quality system for the good laboratory that will endure into the next
      century.

PMID- 9528336
TI  - [Circadian changes in remnant-like particle-cholesterol (RLP-C), and its
      diagnostic value for postprandial increase in remnant lipoprotein in diabetes
      mellitus].
AB  - To investigate whether remnant-like particle-cholesterol (RLP-C) increases in the
      postprandial state, and if so, whether such response can be used for detecting
      postprandial increase in remnant lipoprotein, we measured RLP-C levels at two
      points (before breakfast, and after lunch), or seven points (before and after
      each meal, and midnight) in 36 diabetic patients. delta RLP-C was calculated by
      subtracting RLP-C level before breakfast from that at each point. delta RLP-C
      after lunch was defined as delta RLP-CL and maximum delta RLP-C as delta RLP
      Cmax. Daily profiles of RLP-C (n = 22) showed that RLP-C increased during the
      daytime in 6 patients (27.3%; responders), but not in the others (nonresponders).
      In the histogram of delta RLP-Cmax, we could easily distinguish responders (delta
      RLP-Cmax = 6 approximately 12 mg/dl) from nonresponders (< 4 mg/dl). By using
      delta RLP-CL of 4 mg/dl as the cut-off value, we could also separate two groups
      without overlap. With this cut-off value, 11 out of 36 patients (30.6%) were
      diagnosed as responders. High performance liquid chromatography (HPLC) analysis
      with cholesterol-monitoring revealed that VLDL-sized RLP increased markedly after
      lunch in responders. In conclusion, RLP-C increases in some diabetic patients,
      and delta RLP-CL is useful for detecting postprandial increase in remnant
      lipoprotein.

PMID- 9528337
TI  - [DNA and RNA contents of megakaryocytes using acridine orange staining].
AB  - We developed a new microfluorometric method to measure the DNA and RNA contents
      of individual megakaryocytes using acridine orange (AO) staining in human bone
      marrow smears. Some bone marrow smears were fixed with ethanol and treated with
      pretreatment solution and then stained with an AO staining solution. The DNA
      content was assayed by measuring the green fluorescence and the RNA content was
      assayed by measuring the red fluorescence under B excitation with
      microfluorometer using peripheral lymphocytes as the control. The ploidy peak was
      shown to be 16N in all of 5 normal controls, but it was 8N in the patient with
      refractory anemia with excess of blasts in transformation (RAEB-T). There was not
      difference in the RNA content/DNA content ratios (RI) between each ploidy in the
      normal controls. The RI of the patient with RAEB-T was lower than that of the
      normal controls. The measurement of the DNA-RNA contents may be useful as a new
      megakaryocytic parameter.

PMID- 9528338
TI  - [The data-base including digitized morphologies for clinical testing of bone
      marrow samples using personal computer].
AB  - Clinical testing of bone marrow is essential for diagnosis and treatment of
      hematopoietic disorder. It is sometimes difficult to provide an accurate
      morphological explanation of bone marrow cells in the reports. Various methods,
      such as detailed descriptions or sketches of the cells have been attempted to
      accurately describe the results to clinicians. However, these descriptions and
      sketches may vary depending on the individual. To resolve this problem, a data
      base including digitized microscopic examinations using a personal computer for
      tested bone marrow samples has been developed. This system enables accurate
      reporting of cellular morphology by printing out colored figures. Moreover,
      chronological data may be easily displayed and reviewed on the screen. To assess
      those functions and the quality of print outs showing cellular morphologies, a
      questionnaire survey evaluating this system was conducted. As a result, a fairly
      good assessment was given to the print outs showing various morphologies
      including leukemic cells, infiltrated tumor cells and some cytochemical staining
      methods (peroxidase, esterase and periodic acid Schiff reaction). However, a few
      respondents suggested that expression color in print outs of minute morphologies
      such as chromatin strands, nucleoli and a few azurophil granules were incomplete.
      As for data-base functions, responses to the questionnaire were fairly good. In
      conclusion, this attempt is very useful and practical for clinical testing of
      bone marrow samples.

PMID- 9528339
TI  - [Clinical evaluation of RT-PCR method for detection of HCV-RNA: second report
      availability of RT-PCR system using PCR internal control for detection of HCV-RNA
      and the influence of interfering substances on the detection].
AB  - The COBAS Amplicor system is an automated diagnostic PCR system which contains a
      PCR internal control (P. I. C.) template to monitor the amplification. The
      applicability of COBAS Amplicor HCV was examined using sera of patients with
      hepatitis. Furthermore, the effects of possible interfering substance (total
      protein, triglyceride, hemoglobin, glucose, total bilirubin, heparin, lysis
      reagent including guanidium) on HCV-RNA detection were investigated. The
      sensitivity of COBAS Amplicor HCV was equivalent to the manual method of Amplicor
      HCV, moreover all of the results in 54 clinical samples analyzed on both COBAS
      Amplicor HCV and Amplicor HCV were in agreement. Detection sensitivity of HCV-RNA
      decreased in the presence of total bilirubin and heparin. Ten and 25mg/dl of
      total bilirubin affected HCV-RNA detection but did not affect P. I. C. This
      result suggested that total bilirubin interfered with the protein denature caused
      by the lysis reagent. Fifteen U/ml of heparin in the sample completely inhibited
      amplification both of the HCV-RNA and P. I. C. One U/ml of heparin did not affect
      amplification, but heparinized blood samples should not be used for the detection
      of HCV-RNA. To examine the effect of possible carry over contamination on the
      lysis reagent which contains guanidium, various concentrations of lysis reagent
      in P. I. C. were tested. RT-PCR was inhibited by 1/500 volume contamination of
      lysis reagent in specimen diluent. Other substances did not affect the
      sensitivity. Our results indicate that the carryover contamination of lysis
      reagent cause more "false negative" results than interfering substances in sera.
      In conclusion, HCV-RNA detection system containing P. I. C., such as COBAS
      Amplicor HCV, will become a very useful to differentiate "false negative" and
      "true negative" result.

PMID- 9528340
TI  - [Clinical usefulness of lectin-reactive fraction of alpha-fetoprotein in
      hepatocellular carcinoma].
AB  - Alpha-fetoprotein (AFP) is well known as a tumor marker of hepatocellular
      carcinoma (HCC). AFP shows micro heterogeneity because of a structural variance
      in its sugar chain, and the sugar chain obtained from HCC patients has a high
      affinity to lectins such as Lens culinaris agglutinin. The lens culinaris
      agglutinin A-reactive fraction of alpha-fetoprotein (AFP-L3) was detected by a
      sensitive method using lectin-affinity electrophoresis coupled with antibody
      affinity blotting. Of 62 HCC patients examined before initial therapy, 23
      patients (37.1%) had an AFP-L3 level greater than 15%. In contrast, none of the
      patients with liver cirrhosis or chronic hepatitis tested were positive for AFP
      L3. Seven (26.9%) of 26 patients with small HCC less than 2 cm in diameter
      measured on ultrasonography or computed tomography showed elevated AFP-L3 levels.
      Because there was no correlation observed between AFP-L3 and PIVKA-II, the
      combined measurement of these two complementary markers appeared to be useful in
      the diagnosis of HCC. When the results of both assays were combined, 34 (54.8%)
      of the 62 patients with untreated HCC showed elevated levels of one or both
      markers. The use of both markers together with imaging modalities during regular
      follow-up of chronic liver disease patients who are at high risk for HCC might be
      of great benefit.

PMID- 9528342
TI  - [The immunoreactivity studies of the idiopathic inflammatory myopathy over the
      past three years in our laboratory].
AB  - Biopsied skeletal muscles from patients with inflammatory myopathy (6 cases of
      polymyositis (PM), 2 cases of dermatomyositis (DM), 5 cases of collagen disease
      with polymyositis and a case of allergic granulomatous angitis) were examined by
      comparing immunostained infiltrated cells at perivascular, perimysial and the
      endomysial sites as well as examining the histochemical findings on serial frozen
      sections from cases examined by our laboratory over the past three years. CD68
      was used for macrophage, L26 for B lymphocytes, CD4 and CD8 for T lymphocytes.
      Expression of HLA-ABC was examined for Class I antigen and HLA-DR for Class II
      antigen on the muscle fibers. Many macrophages and CD8-positive T lymphocytes had
      infiltrated the endomysium in PM. Many CD4-positive T lymphocytes and L26
      positive B lymphocytes had infiltrated perivascular sites in DM. These results
      were almost the same as those in many other reports. HLA-ABC was positive on the
      muscle sarcolemma in all cases. However, the expression of HLA-DR was not
      identical in all cases. It is useful to determine the diagnosis and consider a
      pathogenesis of inflammatory muscle diseases to analyze the infiltrated cells and
      the site of infiltration even in case showing few of infiltrating cells and
      necrotic fibers.

PMID- 9528341
TI  - [Immunohistochemical study on keratin no. 8, 18 and 19 expression of carcinoid
      tumors].
AB  - The purpose of this study is to evaluate keratin expression in neuroendocrine
      cells and carcinoid tumor of the gastrointestinal tract and lung. Neuroendocrine
      cells in the lung and the gastrointestinal tract reacted with low-molecular
      keratin strongly, but not with high-molecular keratin. The low-molecular keratin
      expression of carcinoid tumor in the lung and the gastrointestinal tract, which
      varied in degree, were identical to that of neuroendocrine cells. Keratin 8 and
      18 were found abundantly in neuroendocrine tumor and carcinoid tumor of the
      gastrointestinal tract, and in a lesser amount in carcinoid tumor of the lung,
      whereas keratin 19 was found in all cases with variable amounts. Based on these
      results, the combination of antibodies for several types of keratin is useful for
      examining keratin expression as a marker of epithelium in carcinoid tumor.

PMID- 9528343
TI  - [Adult multiple coronary aneurysms of Kawasaki's disease's sequelae; two autopsy
      cases].
AB  - Coronary aneurysm in Kawasaki's disease (Acute febril infantile mucocutaneous
      lymph node syndrome, MCLS) may cause sudden death in childhood and ischemic heart
      disease in adults. We encountered two adult autopsy cases of Kawasaki's disease
      with multiple coronary aneurysms. The first case was a 56-year-old man who
      hospitalized due to recurrent syncope since 51 years of age. At age 55 coronary
      angiography (CAG) had shown multiple aneurysms in the left and right coronary
      artery. In September 1991, he developed chest pain and was brought to the
      hospital, almost dead on arrival (DOA). The patient died later the same day
      despite cardiopulmonary resuscitation. Autopsy findings showed cardiomegaly (470
      g) with multiple coronary aneurysms of three coronary arteries. Microscopically,
      intimal thickening and medial thinning were found in the aneurysmal wall with
      calcification and disruption of the internal elastic lamina. The second case, a
      28-year-old man had been diagnosed with rheumatic fever and mitral regurgitation
      at 4 years of age. Coronary aneurysms were noted on CAG at 26 years of age. In
      April 1992, he developed fever and was admitted to a local hospital where he was
      diagnosed with infectious endocarditis. After his being transferred to our
      hospital, disturbance of consciousness suddenly developed and he died in
      September 1992. Autopsy findings showed cardiomegaly (430 g) with left
      ventricular hypertrophy and multiple coronary aneurysms in left anterior
      descending coronary artery and left circumflex coronary artery. The aneurysmal
      wall showed intimal thickening and medial thinning with multiple recanalizations
      of occlusive lumina and fibrous intimal thickening. The mitral valve showed mild
      fibrosis and calcification without valvular deformity. There was no evidence of
      bacterial endocarditis. Both cases were finally diagnosed as Kawasaki's disease.
      Ischemic heart disease or lesions related to coronary aneurysm in Kawasaki's
      disease may show an increased incidence in the near future. Kawasaki's disease
      should have been followed even in adulthood after treatment in childhood.

PMID- 9528344
TI  - [Giant platelet-like cell fragments produced from abnormal promyelocytes in acute
      myelogenous leukemia].
AB  - A 38-year old man was transmitted to our hospital because of his pneumonia and
      disconsciousness. Laboratory data showed leukocytosis (32,500/microliter), mild
      anemia, and decreased platelet count (6.7 x 10(4)/microliter). The bone marrow
      aspiration revealed the presence of 40% blastoid cells and cytogenetic study
      showed abnormal karyotype, 45, X, -Y, t(8; 21) (q22; q22), indicating acute
      myeloid leukemia (AML, M2). Furthermore, on the microscopic observation, cell
      fragments resembling giant platelets were observed which were positive for
      myeloperoxidase, and several fragments connected with abnormal promyelocytes
      through thin cytoplasm. These results suggested these cell fragments may be
      produced from abnormal promyelocytes in this case.

PMID- 9528345
TI  - [Pagetoid spread of intratubular germ cell neoplasia into rete testis forming
      tumor-like mass].
AB  - Intratubular germ cell neoplasia (ITGCN) is the preinvasive phase of testicular
      germ cell tumors. ITGCN can spread into the rete testis in a pagetoid manner, but
      there are very few published data about this phenomenon. Furthermore, the tumor
      like mass formed by ITGCN with pagetoid spread into the rete testis has not been
      documented to date, and the present case is the first to be reported. A tumor
      like mass was found close to the superior pole of the left testis in a 39-year
      old male and was unrelated to the epididymis. Three other nodules of seminoma
      surrounded by fibroconnective tissue existed next to the mass. Histological
      sections revealed ITGCN which was characterized by the presence of large and
      polygonal germ cells exhibiting clear cytoplasm with distinct cell borders. The
      cytoplasm was rich in glycogen and the cell membrane was immunohistochemically
      positive for placental alkaline phosphatase. The nuclei had less coarse chromatin
      than that of seminoma. ITGCN cells spread in between the lining epithelium of the
      rete and the basement membrane. This characteristic spread was consistent with
      pagetoid spread into the rete testis.

PMID- 9528346
TI  - [Convulsions in relation to polycythemia: literature review and case
      description].
AB  - Polycythemia--characterized by an excessive number of erythrocytes--is a rare
      disease in the dog with a chronic progressive course and unspecific symptoms.
      There are several forms: a primary, a secondary adequate or a secondary
      inadequate polycythemia. The clinical workup is done step by step and after
      stabilization of critical patients, the remaining therapy must address the
      primary cause. We report on a five year old male Leonberger dog suffering from
      secondary, inadequate polycythemia. He was presented with apathy, gait
      disturbances and disorientation. On the basis of the diagnostic workup a
      pathological process in the kidneys was postulated. Initially focal seizures
      became generalized later, most probably because of formation of a forebrain
      thrombus with secondary hypoxia. Even after emergency treatment the general state
      deteriorated. The course indicated possible sepsis. Because of the critical
      picture with secondary complications and the poor prognosis, the dog was
      euthanised. The histopathological results showed T-cell renal lymphoma and
      secondary injury to the forebrain.

PMID- 9528347
TI  - [Case report: oral malignant melanoma in an 11-month-old Dobermann].
AB  - Oral malignant neoplasms are very common in old dogs. The prognosis of oral
      malignant melanoma (MM) for long-term survival is poor, because of early
      metastasis and delayed diagnosis. Oral MM in immature dogs is rare. A case of
      oral MM in an immature dog is described. The diagnostic workup includes
      radiographs of the tumor and thorax, a cytologic examination of the regional
      lymph nodes and a biopsy of the tumor. The therapy with the best chance of
      success is the radical surgical excision of the tumor.

PMID- 9528348
TI  - [What is your diagnosis? Diaphyseal transverse fracture of the radius and ulna
      (distal third of the metaphyseal transition). Osteopetrosis].

PMID- 9528349
TI  - [What is your diagnosis? Feline urologic syndrome].

PMID- 9528350
TI  - [Determination of beta-hydroxybutyrate in milk using test strips: a new aid for
      the diagnosis of subclinical and clinical ketosis in the cow].
AB  - In order to evaluate a dipstick test for the semi-quantitative determination of
      beta-hydroxybutyrate (BHB) in milk, we determined the BHB content in milk samples
      of healthy and ketotic high yielding dairy cows with the dipsticks. BHB was
      analysed on an analyser in 39 of these milk samples as well as in 88 blood
      samples which were drawn when milk samples were obtained. There was a strong
      correlation between milk BHB values which were determined with the two methods (r
      = 0.92; BHB quantitative = -9.9 + 1.25 x BHB dipstick value). Although BHB
      concentration in plasma is much higher than in milk, the correlation between
      plasma BHB, determined on an analyser, and the dipstick test results in the
      corresponding milk samples was also quite strong (r = 0.84; plasma BHB in mmol/l
      = 0.23 + 0.009 x milk BHB in mumol/l, determined with dipsticks). The dipstick
      test is suitable for the diagnosis of clinical ketosis and for monitoring the
      energy status of high yielding dairy cows.

PMID- 9528351
TI  - ["With creatures, trademark"].

PMID- 9528352
TI  - [P450: new functions and application to practical sciences].

PMID- 9528353
TI  - [New transcriptional apparatus in plastids of higher plants].

PMID- 9528355
TI  - [Binding of viral oncogenic proteins and PDZ domains of cellular proteins].

PMID- 9528354
TI  - [Bioregulatory functions of methylsphingosines: in relation to sphingolipid
      signaling pathway and on approach of introducing sphingolipid-based drugs].

PMID- 9528356
TI  - [Epilepsy and glutamate transporters: study of mice lacking a glutamate
      transporter and other recent advances].

PMID- 9528357
TI  - [Klotho mice and klotho gene].

PMID- 9528358
TI  - [Applications of the computational structural biology to the genome sequence
      analysis: recent trends in Europe and USA].

PMID- 9528359
TI  - [Review of pH measurement (2): Practice of pH meter based on glass electrode
      method].

PMID- 9528360
TI  - [Time for registries in perinatology].

PMID- 9528362
TI  - [Treatment of acute myocardial infarction--thrombolysis or emergency PTCA?].

PMID- 9528361
TI  - [Anxiety and depression in cancer patients].

PMID- 9528363
TI  - [Angioplasty in acute myocardial infarction].
AB  - 20 patients with acute myocardial infarction and a medical history of less than
      six hours were treated with immediate percutaneous transluminal coronary
      angioplasty. The median time from start of symptoms until establishment of
      reperfusion of the infarct related artery was 190 minutes, and the time from
      admission to insertion of the balloon was 52 minutes. Angioplasty was successful
      in all patients, with no serious complications. All patients experienced pain
      relief immediately after angioplasty. No patients died or had further
      infarctions. None needed hospitalization during the first three months of follow
      up. Eight patients had an exercise test between five and seven days after
      angioplasty and the other 12 at their six-week check up; there were no signs of
      ischemia or anginal pain. Measurement of global ejection fraction one week and
      six weeks after treatment showed median normal values and no significant changes
      (58% versus 57%). Myocardial perfusion imaging was carried out in eight patients
      both before hospital discharge and six weeks later. Normalization and improvement
      was seen in six patients using this method, whereas the perfusion was found
      unaltered in two patients. Hibernation or stunning, or both are suggested as
      possible explanations for this. We found the method highly effective and safe in
      selected patients.

PMID- 9528364
TI  - [Thrombolytic therapy in acute myocardial infarctions].
AB  - Data on all patients with acute myocardial infarction who were treated in Harstad
      District Hospital in 1995 were analysed. Of the 170 patients, 24% received
      thrombolytic treatment. Thrombolytics were withheld from 15% of the patients,
      although there were no contraindications present. Thrombolytics were administered
      two hours and 18 minutes (mean) after admission to hospital and seven hours after
      the onset of symptoms. 54% of the patients were admitted to hospital within six
      hours and 73% within 12 hours. In-hospital delay before the administration of
      thrombolytics is too long. In Norwegian hospitals this factor has only been
      analysed to a minor degree. Despite a fairly standardized treatment regimen for
      thrombolytics, how frequently it is used probably varies from hospital to
      hospital. There is great potential for improving thrombolytic treatment. The
      results of our analyses have resulted in an extensive change in routine in our
      hospital.

PMID- 9528365
TI  - [Occurrence of anxiety and depression in cancer patients. An investigation at the
      Norwegian Radium Hospital].
AB  - The prevalence of anxiety and depression was evaluated in 716 unselected
      hospitalised patients and out-patients seen at the Norwegian Radium Hospital
      using the Hospital Anxiety and Depression Scale (HADS), the EORTC QLQ-C33 and an
      ad hoc designed questionnaire, the latter assessing socio-demographic data and
      disease-related parameters. The prevalence of anxiety and depression was 13% and
      9%, respectively, as assessed with the HADS. In the logistic regression analysis,
      none of the disease-related factors remained independent parameters predictive
      for psychiatric distress, whereas a history of previous psychiatric problems and
      impaired social life were correlated both with anxiety and depression. Female
      gender, impaired physical activity and impaired social role function were
      additional predictive parameters for anxiety, whereas fatigue predicted
      depression. Careful attention should be paid to cancer patients displaying these
      significant problems in order to diagnose and treat depression and anxiety
      disorders of clinical importance.

PMID- 9528366
TI  - [Cerebral palsy among children in Nordland 1977-91. Occurrence, etiology,
      disability].
AB  - An increasing prevalence of cerebral palsy has been reported in Sweden and other
      countries. One Norwegian study shows decreasing incidence, another shows
      increasing incidence among preterm children. The aim of this study is to describe
      prevalence of cerebral palsy and its etiology and disability among children in
      Nordland county who were born between 1977 and 1991. Perinatal mortality in the
      county declined from 11 per 1,000 in 1973-83 to 7.9 per 1,000 in 1987-91. 62 boys
      and 31 girls were diagnosed with cerebral palsy. The prevalence was 1.91 in 1977
      81, 1.98 in 1982-86 and 2.05 per 1,000 i 1987-91. Among children with a
      birthweight < 1,500 g the prevalence decreased significantly to; 88.9, 42.7 and
      28.8 per 1,000 respectively. Causative factors and disability are presented.
      Prevalence of cerebral palsy as a measure of quality of perinatal care is
      discussed, and a recommendation for a central register is made.

PMID- 9528367
TI  - [Mortality and risk of cancer in systemic connective tissue diseases].
AB  - The systemic connective tissue diseases represent a broad spectrum of multiorgan
      disorders. This report reviews our current knowledge of mortality and the risk of
      cancer in these diseases. The relationship between clinical manifestations and
      reduced survival in systemic sclerosis, systemic lupus erythematosus and
      polyarteritis nodosa is addressed in detail. Moreover, we outline the increased
      risks of cancer in dermatomyositis and lymphoma in primary Sjogren's syndrome, as
      well as cancer of the bladder in patients with Wegener's granulomatosis who have
      been treated with cyclophosphamide. Finally, the conflicting results regarding
      mortality in temporal arteritis are discussed.

PMID- 9528368
TI  - [Autosomal dominant nocturnal frontal lobe epilepsy. An electroclinical and
      genetic description of a Norwegian family with ten affected members].
AB  - We describe a Norwegian family with clusters of brief nocturnal motor seizures
      with hyperkinetic or tonic manifestations. Seizures started in childhood.
      Neurological examination and neuroimaging were normal. Interictal EEG
      registrations were mostly normal, ictal EEG registrations disclosed left frontal
      epileptiform discharges in two of three patients examined and just shallow
      arousal preceding the attack in one of the three patients. Segregation analysis
      indicated an autosomal dominant inheritance pattern, and the patients were
      subsequently diagnosed as having autosomal dominant nocturnal frontal lobe
      epilepsy, a disorder first described in 1995. A missense mutation in the gene for
      the alpha-4 subunit of the neuronal nicotinergic acetylcholine receptor was
      recently described in an Australian family with this disorder. Our Norwegian
      family proved to have a novel insertion mutation (776ins3) in the same gene. This
      mutation affects the second transmembrane domain (M2) which forms the critical
      section of the ion channel. This is the first case of idiopathic partial epilepsy
      where the underlying molecular defect has been found. The fact that a dysfunction
      of the nicotinergic acetylcholine receptor may give rise to frontal epileptic
      seizures was surprising and may shed new light on the basic mechanisms of
      epileptogenesis. Manipulations of the cholinergic system may open up a new
      therapeutic approach.

PMID- 9528369
TI  - [Solvents and injuries of the nervous system].
AB  - Currently, there is an ongoing debate on the extent of neurotoxic effects caused
      by organic solvents. A brief review of relevant scientific literature on human
      exposure to organic solvents and their effects on the nervous system therefore
      seems useful. Clinical studies of solvent abusers, pathological-anatomical
      studies, and epidemiological studies of workers exposed to organic solvents are
      summarized and discussed. The occurrence of acute and subacute effects on the
      nervous system caused by organic solvents is well documented. Evidence of the
      occurrence of chronic disease in the nervous system caused by organic solvents is
      rather limited, and reversibility has been described even in cases with serious
      dysfunction. Exposure to organic solvents ought to be prevented as far as
      possible, because of the reduced quality of life induced by acute and subacute
      effects. However, physicians are advised to exercise care in the diagnostic
      procedure of these patients and to search for differential diagnoses.

PMID- 9528370
TI  - [Antithrombotic treatment in percutaneous transluminal coronary angioplasty].
AB  - Percutaneous transluminal coronary angioplasty is the most commonly used method
      for coronary revascularization in Norway. More than 3,500 procedures were
      performed in 1997. The presence of atherosclerotic endothelium is a strong
      stimulus to increased haemostasis. During balloon angioplasty, activation of the
      coagulation system is further increased by the trauma caused to the vessel wall.
      Major complications associated with coronary angioplasty include vessel
      occlusion, myocardial infarction, and periprocedural death. Most early
      complications occur as a result of the formation of a thrombus at the angioplasty
      site. Effective antithrombotic treatment is essential to reduce the risk of
      thromboembolic complications during and after percutaneous transluminal coronary
      angioplasty with or without stent implantation. All patients should be treated in
      advance with acetylsalicylic acid. Heparin must be given during the procedure.
      After stent implantation the patient should be treated with a combination of the
      two antiplatelet agents acetylsalicylic acid and ticlopidine. This article
      presents the current practice for using antithrombotic medication in percutaneous
      transluminal coronary angioplasty.

PMID- 9528371
TI  - [Measurement of blood pressure in pregnancy].
AB  - The prevalence of hypertension in pregnancy is 4-10 percent. The most serious
      complication associated with hypertension in pregnancy is pre-eclampsia. In one
      out of ten pregnancies where pre-eclampsia is present very serious complications
      develop in the mother or the foetus, or both. Rising blood pressure remains the
      main indicator of impending pre-eclampsia. The reliability of blood pressure
      measurement is therefore of particular importance in pregnancy. This is
      emphasized by the following characteristics of hypertension in pregnancy: limited
      time to observe the patient; pre-eclamptic complications may be present at any
      stage where there is a rise in blood pressure, and the indications for and
      objectives of treatment of pregnancy hypertension are different from those
      employed in the general population. The measurement of antenatal blood pressure
      should be standardized. It should be carried out by a limited number of well
      qualified health professionals, using only equipment of reknowned quality and
      technical standard. Rising blood pressure in pregnancy indicates pre-eclampsia
      until it has been disproved post partum. Because pre-eclampsia is a placental
      disorder, the foetus may be at risk at any stage in the development of the
      disease. The status of the foetus should therefore be monitored accordingly.

PMID- 9528372
TI  - [Do women need different strategies than men to prevent cardiovascular
      diseases?].
AB  - Though women have a lower absolute risk of disease than men at all ages, almost
      all the risk factors for cardiovascular disease carry the same or higher relative
      risk for women as for men. Moreover, the attributable risk is higher in older
      women than in men. Epidemiologic studies show that recent decreases in coronary
      heart disease mortality are in some cases greater among women than men.
      Interventional studies show that women appear to have as good or better a
      response than men to cholesterol-lowering in secondary prevention.
      Antihypertensive drug therapy is effective in preventing clinical endpoints in
      elderly women. These observations imply that an overall estimation of
      cardiovascular risk in women needs careful consideration. Because established
      therapies appear to be effective in high risk women, postmenopausal and probably
      also elderly women are important target groups for preventive efforts. The value
      of prevention for premenopausal women should not be underestimated, but should on
      the whole be approached through population-based strategies.

PMID- 9528373
TI  - [Transient postischemic myocardial injury--a condition of practical clinical
      significance?].
AB  - After a brief ischemic period, a prolonged phase of cardiac dysfunction develops.
      This transient dysfunction is now known as myocardial stunning. In this article
      we list the pathophysiological conditions in which myocardial stunning is most
      likely to occur in humans, and we discuss how it can be diagnosed. Although
      stunning is a reversible condition, its clinical implications can be life
      threatening. However, knowledge of the mechanisms involved may help improve the
      treatment of patients with myocardial stunning where this occurs after
      revascularization procedures for instance, and after cardiac arrest.

PMID- 9528374
TI  - [Referrals to the Lipid clinic--"appropriate" patients with inadequate
      anamnesis].
AB  - We examined 199 consecutive referrals to the Lipid Clinic at the National
      hospital in 1995 in order to compare referral- and chart data on familial
      hyperlipidaemia, familial cardiovascular disease, diagnosis, and lifestyle. 78%
      of referrals were from general practitioners. Most of the referrals included
      information on familial hyperlipidaemia and cardiovascular disease and on diet,
      but did not specify a lipid diagnosis. Less than half of the referrals included
      information on smoking habits (which was almost always specified in the chart).
      Up to 80% did not include information on alcohol, body mass index and physical
      activity, which was also often missing in the chart. We conclude that the
      referring doctors, and to some extent the clinic physicians, identified patients
      with a familial risk of cardiovascular disease, but they did not appear to
      characterise important lifestyle habits related to cardiovascular risk.

PMID- 9528376
TI  - [The system of house physicians--cooperation is the best solution].

PMID- 9528375
TI  - [Feet--a diagnostic tool?].
AB  - We wanted to test the specific theory behind foot reflexology. Three
      reflexotherapists examined 76 patients of whom they had no previous knowledge.
      They were to localize the patients' problems and complaints by examination of the
      foot soles only; they had no other information about the patients. Each patient
      and the therapist graded problems related to 13 different parts of the body.
      Interrater agreement, measured by weighted Kappa, ranged from 0.04 to 0.22, and
      was significantly better than chance (p < 0.05) for six parts of the body. The
      overall Kappa was 0.11 (95% CI: 0.08-0.14). A score based on a detailed
      examination of the "colon zone" showed no significant difference between patients
      with many or few distal intestinal complaints. Generally, the therapists tended
      to score higher than the patients, thus overdiagnosing problems. The statistical
      agreement may be better than pure chance, but is too low to be of any clinical
      significance.

PMID- 9528377
TI  - [May survival after unexpected prehospital heart arrest in Norway be improved?].

PMID- 9528378
TI  - [To improve quality of our hospitals--new efforts are necessary!].

PMID- 9528379
TI  - [Bleeding complications after spinal and epidural anesthesia].

PMID- 9528380
TI  - [Something to think about--from PEG to MIC-KEY?].

PMID- 9528381
TI  - [Do we take care of alpha-streptococci?].

PMID- 9528382
TI  - [Health and social inequality].

PMID- 9528383
TI  - [Fosamax, statistics and the national agency for drug control].

PMID- 9528384
TI  - [The happy pill and physical therapy].

PMID- 9528385
TI  - [Transcendental meditation and mild hypertension].

PMID- 9528386
TI  - [Internet or Intranet? Yes, please, both!].

PMID- 9528388
TI  - Promoting same-race adoption for children of color.
AB  - Opponents of policies that protect same-race adoption assert that children of
      color are languishing in out-of-home care because they are being restricted from
      entering transracial adoption arrangements. This article argues that transracial
      adoption is not necessary to ensure that children of color are adopted in a
      timely manner and sets forth alternative arguments around six issues: (1)
      policies favoring adoption by foster parents, (2) the availability of same-race
      families to adopt children of color, (3) the abundance of children in out-of-home
      care unavailable for adoption or with special needs, (4) disparities in child
      welfare services related to ethnicity, (5) misleading data on the numbers of
      children of color who are in foster care, and (6) poverty as an underlying cause
      of out-of-home placements. This article briefly presents the history of the
      transracial adoption controversy and discusses its current status; counters
      assertions typically used to oppose same-race adoption policies for children of
      color; summarizes the positions of several social work organizations regarding
      adoption and race; and makes recommendations for education, policy, research, and
      practice.

PMID- 9528387
TI  - Investigations into mechanisms modulating proliferation, differentiation, and
      apoptosis in cultured liver, adrenal, skin, and bone cells.
AB  - The intricate modulatory roles played by manifold hormones, growth factors,
      cytokines, extracellular calcium concentrations, intracellular second messengers,
      protein kinases, and nuclear poly(ADP-ribose) polymerase in proliferative,
      differentiative, and apoptotic processes have been the subject of investigations
      that were carried out by means of in vitro either primary or secondary/tertiary
      cultures of differentiated epithelial (hepatocytes, keratinocytes, and
      adrenocytes) and connective tissue cells (osteoblasts and fibroblasts) obtained
      from man and/or other mammalians. In most cases, an ad hoc model system, in which
      cells were floated on the top of the growth medium and, hence, could enjoy nearly
      normal respiratory exchanges, was used. Such a system increased cell viability
      and the ability of parenchymal epithelial cells to respond to extremely low
      concentrations of growth factors, hormones, and pharmaco-toxicological agents in
      a way conceivably very close to their behaviour in vivo.

PMID- 9528389
TI  - Mediation in kinship care: another step in the provision of culturally relevant
      child welfare services.
AB  - With rising numbers of children entering the child welfare system and declining
      numbers of available foster homes, the foster care system has increasingly turned
      to placements with relatives to meet the needs of children removed from parental
      custody. Nowhere is this situation more evident than in the African American
      community. But the child welfare system did not invent the concept of kinship
      care. The foundation of current mediation practice can be traced to several
      ancient cultures, including African culture, where the kinship network often
      provided mediation services in the resolution of disputes. As an ethnocentrically
      designed child welfare system grapples with how to best incorporate kinship care
      into its array of services, conflicts between kinship caregivers and the foster
      care system have arisen. It is suggested that the application of mediation to
      conflicts in agency-kinship family relationships can serve as yet another step in
      social workers' efforts to provide culturally relevant child welfare services.

PMID- 9528391
TI  - Making meaning of Alcoholics Anonymous for social workers: myths, metaphors, and
      realities.
AB  - Alcoholics Anonymous (AA), the increasingly popular mutual-help program for
      alcoholics, is often criticized for being just another substitute addiction,
      emphasizing "powerlessness" to already disenfranchised groups, being a religion
      or cult, adhering to a medical model of disease instead of a strengths
      perspective, and other such areas of concern to social workers. Many of these
      interpretations are based on viewing AA as an alternative treatment model or a
      rational service delivery model. This article addresses common critiques of AA by
      offering a way of understanding it as a "normative narrative community," where
      identity transformation takes place through the use of metaphor and storytelling.
      The article suggests alternative meanings of key metaphors, such as
      "powerlessness," describes areas of program strength and potential barriers for
      social workers, and reviews current research on AA effectiveness.

PMID- 9528390
TI  - Psychological and spiritual growth in women living with HIV.
AB  - Women living with HIV and AIDS face tremendous obstacles to wellness, yet many
      find ways to use their experience of HIV as a vehicle for psychological and
      spiritual growth. A qualitative study was conducted to better understand this
      process. Thirty-four women living with various stages of HIV were interviewed.
      Five components were found to be important in their psychological and spiritual
      growth: reckoning with death, life affirmation, creation of meaning, self
      affirmation, and redefining relationships. Implications for social work practice
      and future research are discussed.

PMID- 9528392
TI  - HIV/AIDS in a Puerto Rican/Dominican community: a collaborative project with a
      botanical shop.

PMID- 9528393
TI  - Join us in exploration.

PMID- 9528394
TI  - Case advocacy in child welfare.

PMID- 9528395
TI  - ATOD prevention programs.

PMID- 9528396
TI  - Skeletal maturation of the hand and wrist and its correlation with dental
      development.
AB  - The maturation status of each hand and wrist bone age of 117 12-year-old Southern
      Chinese girls was studied using the Greulich and Pyle Atlas (1959) Method. The
      bone ages were found to range from 12.14 years (scaphoid) to 12.80 years (middle
      phalanx V). The mean and standard deviation of the skeletal age of the hand and
      wrist region were 12.57 years and 1.11 years, respectively. Skeletal maturation
      of 102 of these Southern Chinese girls was correlated to the developmental status
      of their permanent dentition. A statistically significant difference with p <
      0.01 was found between the skeletally above-average and skeletally below-average
      girls. Contrary to previous studies, the skeletally below-average group had on
      average 1.1 more erupted permanent teeth than the skeletally advanced group. In
      addition, there did not seem to be any close relation between apical closure of
      the permanent mandibular canine and bone age of the adductor sesamoid.

PMID- 9528397
TI  - Shear bond strength of ceramic brackets to resin-composite surfaces.
AB  - In this study, two types of ceramic brackets--monocrystalline and polycrystalline
      -were bonded to unroughened and roughened resin-composite discs using a light
      cured orthodontic adhesive, and the bonds tested under shear stress in a
      universal testing machine. There was no significant difference in the shear bond
      strength between the combinations of ceramic brackets, and between the surface
      treatments of the resin composite. A higher frequency of resin-composite fracture
      was observed with the polycrystalline brackets (12/20) than with the
      monocrystalline ceramic brackets (7/20). It is concluded that debonding any type
      of ceramic bracket from a resin-composite surface may cause damage to the resin
      composite itself.

PMID- 9528398
TI  - Prevalence of malocclusion traits in an Australian adult population.
AB  - The prevalence of certain malocclusion traits in an Australia adult population
      was examined in a sample of 113 female and 103 male adult subjects aged between
      18 and 64 years (average age = 38.1 years). If cross-sectional studies of younger
      population groups are to be used for research into the long-term physiological
      effects of malocclusion, it is essential to know if certain and specific
      malocclusion traits are stable over time. In this cross-sectional study, the
      prevalence of many malocclusion traits did not change; however, with advancing
      age, the incidence of posterior crowding, posterior rotations, posterior
      crossbite and anterior irregularity increased significantly.

PMID- 9528399
TI  - Comparison of the shear bond strength of a so-called 'dual-cured glass-ionomer
      cement' and a conventional resin composite used in orthodontic bonding.
AB  - Glass-ionomer cements are a promising bonding alternative to resin composite in
      that they maintain the integrity of the enamel, are easier to debond and prevent
      enamel decalcification adjacent to the bonded bracket. The purpose of the study
      was to compare the shear bond strength of a so-called 'dual-cured glass-ionomer
      cement' (Band-Lok) with a conventional resin composite (Right-On) in bonding
      orthodontic brackets to enamel. The results indicated that: (1) the resin
      composite had a significantly greater mean shear bond strength than Band-Lok; (2)
      the mean shear bond strength of Band-Lok was lower at seven days than at 60
      minutes; (3) there was no significant difference between the mean shear bond
      strength of Band-Lok with and without light curing; (4) all the Band-Lok
      specimens failed at the adhesive/enamel interface; and (5) Band-Lok does not fit
      the definition of a glass-ionomer cement. This study did not support the use of
      Band-Lok as an orthodontic bracket bonding agent; further development is needed
      to improve its bond strength to enamel.

PMID- 9528400
TI  - Perceptions of orthodontic appliances among grade seven students and their
      parents.
AB  - A survey of 468 Grade Seven students and 437 parents in the North Brisbane region
      was undertaken to determine perceptions of orthodontic appliances. Based on
      responses to statements on the survey, a Perception Score was created for both
      students and parents in relation to both fixed and removable appliances. Both
      students and parents had more negative perceptions of fixed appliances than of
      removable appliances. Fixed appliances were perceived to attract more teasing, to
      cause more problems in the maintenance of oral hygiene and to be more painful
      than a removable plate. Respondents also felt that children would have to be more
      careful about what they eat when wearing fixed appliances. Approximately forty
      per cent of students and parents did not know whether teeth could be damaged by
      orthodontic appliances nor whether the appliances would cause discomfort. Parents
      had significantly more negative perceptions of both types of orthodontic
      appliances than did the students. The Perceptions scores were not significantly
      influenced by whether the students attended a private or public sector dentist,
      the frequency of dental visits, any history of orthodontic treatment, nor by the
      parents' level of education and their occupations. A forewarning about
      experiences of orthodontic appliances would better prepare patients and assist
      operators in providing the community with a more comprehensive orthodontic
      service.

PMID- 9528402
TI  - The EDH bracket: a brief history. Eastman Dental Hospital.

PMID- 9528401
TI  - Orthodontic treatment planning for inclusion of the third molar in the dental
      arches: Part I.

PMID- 9528403
TI  - Correlation of sexual maturation with skeletal age of southern Chinese girls.
AB  - The correlation of skeletal maturation with the chronological ages of the onset
      of four secondary sexual characteristics (menarche, appearance of pubic hair and
      axillary hair, and breast development) was studied in a group of 117 Southern
      Chinese girls aged between 11 years, 9 months and 12 years, 3 months, who were
      born and brought up in Hong Kong. The skeletal maturation was assessed from left
      hand and wrist radiographs by the Greulich and Pyle Atlas Method (1959). The
      early maturers in sexual maturation were significantly more advanced in skeletal
      maturity with p < 0.001.

PMID- 9528405
TI  - Dentofacial changes in patients with Class III malocclusions treated by a
      combination of activator and chin-cup appliances.
AB  - The purpose of this study was to examine, on pre-treatment and post-treatment
      lateral cephalograms, the effects of combined activator/chin-cup therapy on Class
      III patients, and to compare mean cephalometric differences noted during
      treatment with untreated Class I subjects. Fourteen females and fifteen males who
      exhibited a Class III malocclusion were the subjects of the study. Direct
      comparison of the mean value changes of the cephalometric variables during
      treatment of Class III patients with untreated Class I subjects revealed that SNA
      increased more and SNB increased less in the Class III patients than in the
      control group, thus improving the ANB angle. At the end of treatment, all
      patients had a positive overjet but a more concave profile. In this study,
      combined activator/chin-cup therapy seemed to induce improvement in those Class
      III patients selected for their moderate condition and treated over a five-year
      period. The changes seemed to indicate growth patterns which imitate those of the
      untreated Class I subjects. Moreover, dentoalveolar compensations helped to
      improve the overjet and conceal skeletal deviations.

PMID- 9528404
TI  - Quantification of ethnic differences in facial profile.
AB  - The concept of facial aesthetics is becoming increasingly important and with the
      expanding application of orthodontic, orthognathic, plastic and reconstructive
      techniques to patients from continually diversifying ethnic backgrounds, it is
      timely that more elaborate methods for the evaluation of facial form are adopted.
      The aim of the present study was to further investigate the use of Fourier shape
      analysis in the quantification of facial profile and to investigate differences
      between racial groups. One hundred and twenty-two undergraduate dental students
      were photographed and surveyed for information pertaining to ethnic origin.
      Student's t-tests revealed significant differences (p < 0.05) in higher-order
      (fourth- and above) Fourier harmonics between male and female profiles, as well
      as between intervention and non-intervention groups. A comparison of multiple
      means test revealed significant differences (p < 0.05) in the third-order Fourier
      harmonic (vertex projection) between the Asian group and three other groups-
      Anglo-Celtic, Eastern European and Western European. Differences correlated with
      convexity in the lower third of the face, which was demonstrated by Fourier
      reconstruction.

PMID- 9528406
TI  - Application of a case-based expert system to orthodontic diagnosis and treatment
      planning.
AB  - Expert systems are being utilised increasingly in medical fields for the purposes
      of assisting diagnosis and treatment planning. A case-based system is a
      particular type of expert system that uses a store of previously treated cases to
      provide the knowledge for solving new problems. The aim of this study was to
      investigate the application of this methodology in the field of orthodontic
      diagnosis and treatment planning. Using a limited group of features, a case-base
      of 300 cases was entered into a case-based expert system shell. A test set of 30
      consecutive cases was then used to test the diagnostic capacity of the system.
      The computer-generated treatment plan matched the actual treatment plan in 24 of
      the 30 cases. The system was also tested for its capacity to handle unusual
      cases. The system has useful potential.

PMID- 9528407
TI  - Case report: non-extraction treatment with functional and mechanical therapy of a
      Class II division 1 malocclusion.
AB  - Non-extraction treatment was carried out for a growing Angle Class II division 1
      patient. Because the patient demonstrated potential growth and all the third
      molars were congenitally missing, the extraction of the four premolars was ruled
      out. A functional appliance (MGA) and cervical headgear were employed
      simultaneously in the first phase of treatment. The second phase was carried out
      by mechanotherapy. As a result, adequate forward growth of the mandible was
      attained and all 28 teeth were kept in good relation with no root resorption and
      healthy periodontal tissue. A better improvement of the profile may have been
      attained had extraction treatment been performed; with non-extraction treatment,
      however, the amount of tooth movement could be minimized, and root resorption was
      not observed. The role of the functional appliance is also important for the
      success of non-extraction treatment in Class II patients.

PMID- 9528408
TI  - The rotation of maxillary first molars, mandibular first molars, and maxillary
      first premolars in acceptable occlusions.
AB  - The rotation of the maxillary molars is considered important in the orthodontic
      treatment of malocclusions. In this study, a computer analysis program was
      developed to examine the rotations of maxillary molars, mandibular molars, and
      maxillary first premolars in casts of permanent dentitions with acceptable
      occlusions. Ninety-three sets of untreated 'acceptable occlusion' models from the
      collection of the Foundation for Orthodontic Research (FOR) were scanned on a
      flat bed scanner. The images were analysed using custom software. Measurements
      were made by relating maxillary first permanent molars to the midline, archform,
      opposite canine, and mandibular first permanent molars. The mandibular first
      molars and maxillary first premolars were also analysed and their rotations
      measured. The mean rotations of the maxillary first molars, measured as the angle
      between a line joining the tips of the buccal cusps and a line tangent to the
      appropriate archwire form (from Ricketts' Pentamorphic Arches) at the first
      molars, were 0.59 and -0.72 degree (positive values represent mesio-lingual
      rotations) for the right and left, respectively. For the mandibular molars, these
      means were 6.34 and 8.40 degrees, respectively. The mean differences in rotation
      between buccal cusp tips of maxillary and mandibular first molars in occlusion
      were 5.75 and 9.12 degrees for the right and left, respectively, with the
      mandibular being more mesio-lingually rotated. The differences between left and
      right were significant for all measurements. The present study brings into
      question the suitability of our present "straight wire" prescriptions in
      producing similar occlusions. It also suggests that scanning models for computer
      analysis may be a practical and precise way to measure similar rotations in
      untreated normal and treated occlusions.

PMID- 9528409
TI  - A new self-curing resin-modified glass-ionomer cement for the direct bonding of
      orthodontic brackets.
AB  - A new self-curing (chemically-cured), resin-modified glass-ionomer cement, Fuji
      Ortho (GC International Japan) is based on the technology of hybrid glass-ionomer
      restorative materials and features chemical adhesion to tooth structure and long
      term fluoride release. These materials do not require acid etching of the tooth
      for adhesion, thereby preserving the integrity of the enamel prisms. This paper
      describes the clinical use of Fuji Ortho for the direct bonding of orthodontic
      (metal) brackets.

PMID- 9528410
TI  - Modern science and the destruction of traditional understandings.

PMID- 9528411
TI  - Guiding occlusal development with functional appliances.
AB  - Functional appliances have been used in orthodontics since their introduction by
      Pierre Robin almost one hundred years ago, however, our understanding of how they
      bring about orthodontic correction is still limited. This article is a brief
      overview of their history, mode of action, advantages and disadvantages, and
      includes the results of a study of attempts to control and minimise their side
      effects using a recent development in functional appliances: the 'Teuscher
      Appliance'. This appliance combines a high-pull headgear with the activator, and
      is designed to reduce the often reported side-effects of functional appliances.
      The skeletal and dentoalveolar effects of treatment with the Teuscher Appliance
      on 40 consecutively-treated patients are reported and illustrated with four
      individual case reports. The results showed that the skeletal effect on the
      maxilla was a retardation of the normal forward and downward growth in 80 per
      cent of the cases, and that mandibular growth in 70 per cent of cases was
      forward. In patients whose mandibular growth was primarily in a vertical
      direction, such growth could be ascribed mainly to posterior rotation of the
      maxilla and/or the fact that the acrylic covering the lower posterior teeth to
      correct a deep bite was removed, promoting the eruption of these teeth and
      increasing the anterior vertical development. The dentoalveolar changes were
      characterised by retroclination of the maxillary incisors in 90 per cent of the
      patients, and were due to insufficient torque control by the built-in torque
      springs, which need further development. The mandibular incisors were well
      controlled by capping. The statistical analysis showed an inverse correlation
      between the initial incisor inclination and the change during treatment. This
      suggests that proclination of the lower incisors, as previously reported, is not
      a contra-indication to functional appliance treatment, provided the appliance is
      correctly designed. Overall, this study showed considerable individual response
      to treatment, and that the occlusal correction occurred through a combination of
      skeletal and dentoalveolar changes.

PMID- 9528412
TI  - A mathematical study of anterior dental relations: Part II, Incisor and canine
      overjet.
AB  - A mathematical model of anterior inter-arch relations was described in a previous
      article. This model is modified and manipulated and, using hypothetical dental
      measurements, results are generated and presented. The present work continues the
      two-dimensional examination of anterior dental relations in the first article,
      the emphasis remaining on incisor and canine overjet. Other authors have started
      by observing ideal occlusions, then have worked backwards to gain ratios of
      preferred maxillary to mandibular teeth widths; this restricts their studies to
      Class I occlusions with complete anterior dentitions and similar anterior form of
      both arches. This paper has no premise of normal or initial ratios. Incorporation
      of multiple factors allows forming and testing of hypotheses of anterior dental
      relations. Many factors influence anterior dental relations in varying degrees.
      Some dental measurement changes examined here are: the sum of teeth widths in
      each arch; spacing; crowding; angle of the arc of each arch and the antero
      posterior buccal relation. Summary tables are presented to aid the prediction of
      the direction of inter-arch response to change in a dental measurement. Some
      inferences are discussed and are presented as a series of principles considered
      valid for this model. The principles may warrant testing with other arch form
      models.

PMID- 9528413
TI  - Application of a case-based expert system to orthodontic diagnosis and treatment
      planning: a review of the literature.
AB  - Computer expert systems are being utilised increasingly in medical fields to
      assist diagnosis and treatment planning. Traditional rule-based expert systems
      have some limitations when applied to orthodontic diagnosis and treatment
      planning. These limitations may be avoided by using a case-based system which is
      a particular type of expert system that uses a stored data bank of previously
      treated cases to provide the knowledge for solving new treatment problems. This
      article reviews the use of expert systems for orthodontic diagnosis and treatment
      planning, outlines the rationale, processes and advantages of case-based systems,
      and gives examples of the application of this technology in medical fields.

PMID- 9528414
TI  - Functional appliances: a mortgage on mandibular position.

PMID- 9528415
TI  - Complications of orthognathic surgery.
AB  - Although orthognathic surgery has now become a routine part of oral and
      maxillofacial surgery practice, concern and apprehension about major jaw surgery
      continues to plague the minds of many orthodontists faced with the prospect of
      referring their patients for surgery. Like all surgery, complications also occur
      with orthognathic procedures, most of which can be prevented by thorough planning
      and careful surgery. In this article a brief overview of the potential
      complications associated with orthognathic surgery is presented for the benefit
      of orthodontists involved in the management of patients undergoing combined
      orthodontic-surgical treatment.

PMID- 9528416
TI  - Second permanent molar extraction and late lower arch crowding: a ten-year
      longitudinal study.
AB  - The purpose of this investigation was to examine lower arch alignment in the long
      term following treatment by second molar extraction. Thirty subjects, treated by
      extraction of four second permanent molars at an average age of 13.9 years, were
      examined five and ten years after extractions. None had any mechanical treatment
      in the lower arch. Twenty had some simple upper arch treatment, including, in
      five cases, extraction of first premolars. The changes in lower arch alignment
      were measured on study models. There was a small average decrease in lower arch
      crowding in the first five years following extraction, and little or no change in
      alignment in the next five years.

PMID- 9528417
TI  - A family case report: disturbances in tooth form and eruption of the second
      premolar.
AB  - This report describes a family who demonstrated anomalies of tooth form and
      eruption of the lower second premolar. Observation of the second premolars
      remaining in the mother's and father's dentitions included ectopic eruption with
      impaction and substantial spacing between the first and second premolars. Four
      siblings were also examined--three boys aged 15, 14 and 12 years, and one girl
      aged 11 years. Anomalies of the second premolar recorded in the males and female
      include: congenital absence, ectopic eruption with impaction, delayed eruption
      and spacing. Associated anomalies included: congenital absence of other permanent
      teeth and spacing. It appears that the defect in tooth form and eruption is of a
      genetic origin, affecting both males and females. The condition(s) did not appear
      to be associated with a syndrome and the human papilloma virus lesions noted in
      all family members were not considered to be related to the dental defects. This
      family demonstrated two anomalies of the lower second premolar: congenital
      absence and disturbance in tooth eruption. The question raised by this case
      report is whether these two anomalies are inherited as separate traits or whether
      failure of tooth eruption is a variation in expression of the same genetic factor
      that results in oligodontia.

PMID- 9528418
TI  - A genetic aetiology for some common dental anomalies: a pilot twin study.
AB  - This pilot study investigated the aetiology of various dental anomalies. Twin
      pair correlations were obtained for the total number of missing, ectopic,
      malformed and rotated permanent teeth which were scored from panoramic
      radiographs of 59 monozygotic (identical) and 42 dizygotic (non-identical) twin
      pairs. All monozygotic (MZ) twin correlations were greater than the dizygotic
      (DZ) twin correlations, suggesting a significant hereditary aetiology. A familial
      history of such common dental anomalies could become a valuable asset in
      treatment planning.

PMID- 9528419
TI  - Post-retention results of spring-loaded posterior bite-block therapy.
AB  - In this study, ten patients who were treated with spring-loaded posterior bite
      blocks (SLPBB), were evaluated over a period of two years in order to test the
      effects of the appliance and the incidence of relapse. Successful treatment with
      SLPBB was achieved in skeletal and dental open bite cases. However, the use of
      acrylic bite blocks for retention during the post-treatment growth period, did
      not prevent relapse.

PMID- 9528421
TI  - Enhancing your practice. Attracting new patients while retaining those you have.

PMID- 9528422
TI  - What to do if IDPR comes to your office. Illinois Department of Professional
      Regulation.
AB  - What should you do if the Illinois Department of Professional Regulations comes
      to your door? First thing, don't panic. Second thing, call your attorney.

PMID- 9528423
TI  - Case report: plasma cell gingivitis A.
AB  - The plasma cell gingivitis condition, an uncommon, nonmalignant lesion, is
      characterized by an offending allergen which causes a massive plasma cell
      infiltration in gingival connective tissue. Occasionally, soft tissue biopsy of
      affected and normal tissues is necessary for proper diagnosis. Blood analysis may
      rule out other systematic disorders with oral manifestations. This case report
      describes the condition.

PMID- 9528424
TI  - 60 years of women in dentistry. Ten CDS members who've met life's challenges.

PMID- 9528425
TI  - The key to scheduling profitably.
AB  - Smart scheduling in the dental office can help staff use their time and resources
      more efficiently and increase the practice's profitability. Communication among
      staff members is key to achieving this goal.

PMID- 9528427
TI  - What is dental malpractice? The elements of a malpractice claim.
AB  - Malpractice is a broad designation that generally encompasses any improper
      conduct in the performance of a professional's duty. Most often, it is considered
      synonymous with the term "negligence."

PMID- 9528426
TI  - N2O. How safe is it?

PMID- 9528428
TI  - Narcissism and dentistry.

PMID- 9528429
TI  - Fear in the dental chair.
AB  - About a quarter of adults avoid regular dental examinations as a result of
      childhood experiences. The dentist who is sensitive to these fears will provide
      more than much needed treatment.

PMID- 9528430
TI  - Can you judge crooks by their cover?

PMID- 9528431
TI  - Two Chicago dental schools: meeting the needs of the elderly and the profession.

PMID- 9528432
TI  - How to design an effective practice brochure.
AB  - The practice brochure is an effective marketing tool. But should you do it
      yourself or hire a designer? Each option has its pros and cons, as this marketing
      expert explains.

PMID- 9528434
TI  - Where's the access?

PMID- 9528433
TI  - Diagnosis and treatment planning for placing, restoring and maintaining dental
      implants: Part V.

PMID- 9528435
TI  - Area dentists comment on managed care, esthetic dentistry and patient fears.

PMID- 9528436
TI  - Fighting child abuse from the dental office.

PMID- 9528437
TI  - Preparing for medical complications in the dental office.

PMID- 9528439
TI  - Eating disorders: the untold story.

PMID- 9528438
TI  - Treating buccal dehiscence defect by a polylactic acid membrane barrier: a six
      month case report.

PMID- 9528440
TI  - The trouble with men.

PMID- 9528441
TI  - Use of a bioresorbable pin and membrane barrier for guided-tissue regeneration.

PMID- 9528442
TI  - The future is now. How advances in dental technologies are changing the way you
      practice.

PMID- 9528443
TI  - Restorative dentistry--a material issue. Interview by Rick Asa.
AB  - Recent technological advances in materials have changed the face of restorative
      dentistry. But, as these experts note, some things remain the same.

PMID- 9528444
TI  - American dental education: contributions of Russell A. Dixon.

PMID- 9528445
TI  - The Spang Center: an oasis of care. Interview by Rick Asa.

PMID- 9528446
TI  - PEERS Chicago. Prevention, Education, Ethics, Resources and Support.

PMID- 9528447
TI  - Dental malpractice: practical tips on avoiding a dental malpractice claim.
AB  - With a few simple strategies, dentists can avoid the expensive trauma of
      malpractice litigation. Sometimes it's just a matter of maintaining good records.

PMID- 9528448
TI  - Your young patients. An update on what's new in pediatric dentistry.

PMID- 9528449
TI  - Behavior management of the special child.

PMID- 9528451
TI  - Oral protection for equestrians.
AB  - Facial injuries are common among those who ride horses. However, the use of
      custom-made mouth guards is not promoted by those in the equestrian industry.

PMID- 9528450
TI  - Defining biologic width in crown lengthening.
AB  - Clinicians must be very careful when making clinical evaluations of the need for
      crown lengthening procedures and margin placement and subsequent determinations
      about the dento-gingival junction and biologic width. Clinicians have tried to
      standardize a biologic phenomenon and assign the same standard to all patients
      regardless of the circumstances.

PMID- 9528452
TI  - The future of dental school clinic patient care.
AB  - Dental school clinics once served a single purpose: To provide clinical
      experience for the school's students. Clinic fees were low, the patient base
      generally consisted of those who could not afford private practice fees and long
      waits were expected. But times are changing. Dental school clinics are becoming
      more competitive in an effort to provide a solid financial base for the schools-
      in addition to their traditional educational mission.

PMID- 9528453
TI  - Preaching to the choir. Chicago hosts first AIDS conference for dentists.

PMID- 9528454
TI  - Dentists put pedal to the metal on information superhighway.
AB  - The information highway takes off in directions only dreamed about five years
      ago. Are you ready? Or will technology leave you in the dust?

PMID- 9528455
TI  - Diagnosis and treatment planning for placing, restoring and maintaining dental
      implants.

PMID- 9528456
TI  - Volunteerism: dentistry's helping hand works both ways.
AB  - The rewards of volunteering are as varied as the organizations in and around
      Chicago that serve special populations. Some of these patients have special
      needs, others simply cannot afford to pay for their own dental care. Whatever the
      reason, the outcome always seems to be the same: Patients are treated and
      dentists find that maybe they chose this profession for something more than just
      a way to earn a paycheck.

PMID- 9528457
TI  - Preventive dentistry in Illinois.
AB  - Success in preventive dentistry requires much more than community water
      fluoridation, dental sealants, fluoride supplements and dental health education.
      The scope of preventive dentistry should include oral cancer prevention,
      orofacial injury control, craniofacial anomalies, malocclusion, and the early
      detection of systemic disease with oral manifestations. The Division of Dental
      Health has developed preventive programs to address a majority of these health
      problems. The State of Illinois can be considered in the forefront of preventive
      dentistry. It has more than 85% of its population served by optimally fluoridated
      drinking water, 75,000 children participating in fluoride mouthrinse programs,
      established dental sealant programs and mouthguard programs, and the availability
      of innovative programs that address a wide variety of oral health concerns. These
      programs and others being conducted by the Illinois State Dental Society and in
      private dental offices are providing a significant improvement in the oral health
      status for all residents of Illinois.

PMID- 9528458
TI  - Dentists who volunteer abroad.

PMID- 9528459
TI  - Diagnosis and treatment planning for placing, restoring and maintaining dental
      implants: Part III.

PMID- 9528460
TI  - Managed care: a call for strategic management in the dental office.
AB  - Strategic management of any business will enable it to prosper in challenging
      times of change. Strategic planning is not characteristically found only in large
      corporations. Indeed, small business, such as solo private practices, can gain
      much from the process. The successful practice is one that is proactive rather
      than reactive; it has learned to become the beneficiary of change, rather than
      its victim.

PMID- 9528461
TI  - Revamped ADA program seeks dentistry's seal of approval.

PMID- 9528462
TI  - Diagnosis and treatment planning for placing, restoring and maintaining dental
      implants: Part II.

PMID- 9528463
TI  - Benign cementoblastoma: report of case.

PMID- 9528465
TI  - AGD: changed bylaws can change again. Academy of General Dentistry.

PMID- 9528464
TI  - The obligation to treat patients who are HIV-positive.

PMID- 9528466
TI  - Young dentists: what do they expect of organized dentistry?

PMID- 9528467
TI  - Getting started: real life stories point the way to success.

PMID- 9528468
TI  - The ADA Washington office: dentistry's voice on the Hill.

PMID- 9528469
TI  - Record keeping key liability issue.

PMID- 9528470
TI  - Diagnosis and treatment planning for placing, restoring and maintaining dental
      implants: Part IV.

PMID- 9528471
TI  - Acer and AIDS addressed again.

PMID- 9528472
TI  - The strange case of David Acer: myth and reality.

PMID- 9528473
TI  - Fuzzy science: a look at CDC's analysis of the Acer case.

PMID- 9528474
TI  - Managing the HIV-positive dental patient in the general dental office.

PMID- 9528475
TI  - The legal considerations of referring patients who have AIDS.

PMID- 9528476
TI  - HIV and AIDS in dental practice: an evolution in care.

PMID- 9528477
TI  - In defense of disinfection ... the handpiece study.

PMID- 9528478
TI  - Thoughts at large. Who cares if they outlaw amalgam?

PMID- 9528479
TI  - Infection control: patient survey.

PMID- 9528481
TI  - Child physical abuse: case report of a dentist's experience.

PMID- 9528480
TI  - Case report.

PMID- 9528483
TI  - AIDS update.

PMID- 9528482
TI  - Caries risk assessment.
AB  - Caries risk assessment is a relatively simple, yet cost effective method to
      evaluate the oral condition likely to produce carious lesions in both children
      and adults. This procedure can also indicate current caries activity in a
      patient. The assessment can provide the foundation for a scientifically-based
      preventive dental practice. The cost and contents of two different caries risk
      assessment kits are discussed.

PMID- 9528484
TI  - Thoughts on periodontal disease.

PMID- 9528485
TI  - Sjogren's syndrome: the general dentist's role.

PMID- 9528486
TI  - The importance of oral care in HIV infection.

PMID- 9528487
TI  - AIDS.

PMID- 9528488
TI  - Short term volunteer health care in developing countries.

PMID- 9528489
TI  - Better dentistry by design.

PMID- 9528490
TI  - Contact with the world and to the point. Contact Point celebrates 70 years.

PMID- 9528491
TI  - The impact of health care reform on dental education.

PMID- 9528492
TI  - The FDI. Extending dental knowledge to the four corners of the world. Federation
      Dentaire Internationale.

PMID- 9528493
TI  - Opportunity knocks.

PMID- 9528494
TI  - Numb & number.

PMID- 9528495
TI  - Parchment's progress.

PMID- 9528496
TI  - Monitoring quality.

PMID- 9528497
TI  - Wellness and dentistry. A delicate balance.

PMID- 9528498
TI  - Doctors of the mouth.

PMID- 9528499
TI  - How many dentists are too many?

PMID- 9528500
TI  - Women. You've come a long way tooth fairy.

PMID- 9528502
TI  - Ethics 101. A look at what's happening in ethics today.

PMID- 9528501
TI  - Brush with destiny. A social history of the toothbrush.

PMID- 9528503
TI  - Dental electronic analgesia as an alternative mode of pain control.

PMID- 9528504
TI  - Endodontics in a new light.

PMID- 9528505
TI  - Maximizing esthetics. Maximizing support. Maximizing longevity.

PMID- 9528506
TI  - SFV dental office TB protocol. San Fernando Valley.

PMID- 9528507
TI  - Is nursing becoming too technical?

PMID- 9528508
TI  - Initial assessment in the A & E department.
AB  - In this second paper on the work of Accident and Emergency (A & E) nurses, a
      general overview of nursing assessment in the A & E department at the point of
      initial nurse patient contact is put forward. This is rooted in nurses' accounts
      of the ways in which nursing work is talked about and accomplished within the A &
      E setting. Again it should be noted that this paper describes the ordinary rather
      than the extraordinary and should hold no surprises for those familiar with such
      work.

PMID- 9528509
TI  - Mock drunk driving crash: an exercise in injury prevention.
AB  - Alcohol is a contributing factor in many car crashes around the world (Emergency
      Nurses Association 1995). Emergency nurses care for the victims of these crashes
      and are in an ideal position to share their experience with the community. A mock
      drunk driving crash illustrates the realities and consequences of impaired
      driving (Huber et al 1995). This event may be staged at secondary schools,
      universities or elsewhere in the community. Students from the participating
      agency play the roles of the victims. Police, fire, pre-hospital emergency care
      personnel and highway traffic patrol are dispatched to the crash scene, where
      they perform their duties as they would in a real situation. A follow-up session
      at the hospital or in a classroom provides an opportunity to address the
      consequences of drunk driving and discuss strategies for prevention.

PMID- 9528510
TI  - The empowerment of children: who decides?
AB  - While the health and well-being of children in general continues to improve,
      there remains a definitive health care divide. In the UK one-quarter of all
      children live in abject poverty, their lives shortened by the deleterious effects
      of poverty on life expectancy. Regardless of their background, children are
      united by common features of childhood, one being the concept of children as
      immature adults and, therefore, incapable of making important decisions. Such
      concepts are not conducive to the development of children as rational individuals
      with the ability to reason and make appropriate judgements. Thus, it is the aim
      of this paper to identify the internal and external forces which prevent the
      empowerment of children, more specifically the empowerment of children to make
      decisions about health care choices. The presumption is that the exposure of
      obstructive elements will reveal the vital components required to provide
      children with the privilege of choice. Although legislation such as the Children
      Act 1989 has sought to empower children by recognizing that the child has a
      'voice', there remains the potential for conflict to arise when the child 'fails
      to conform' to popular opinion. Moreover, it is possible that without explicit
      empowerment, those in a position of assumed power will seek to overrule the
      child.

PMID- 9528511
TI  - Victims of violent crime.
AB  - Violence is the leading cause of serious facial injuries in the UK. This paper
      outlines how and why the police and hospitals should, together, be doing more to
      protect the increasing numbers of victims. This paper is reproduced by kind
      permission of the author and the publishers of Policing Today, which is the
      journal of the Association of Chief Police Officers of England, Wales and
      Northern Ireland, Vol 3, Issue 2, June 1997. The majority of studies described in
      this paper were carried out by Professor Shepherd's research team at the
      University Hospital of Wales in Cardiff. Professor Shepherd chaired the Victim
      Support working party which produced the national guidelines 'Treating victims of
      crime', circulated in 1995 to all family doctors and A & E departments in the UK.

PMID- 9528512
TI  - A & E nurses' constructs on the nature of nursing expertise: a repertory grid
      technique.
AB  - The concept of nursing expertise has been the focus of considerable debate since
      the early 1980s, yet an agreed definition of the concept and the precise criteria
      by which it can be evaluated remains elusive. This paper will describe an
      exploratory study into A & E nurses' constructs of the nature of nursing
      expertise. Seven first level Accident and Emergency (A & E) nurses were
      interviewed using Kelly's Repertory Grid Technique. Each was asked to provide
      examples of nurses with whom they are working or have worked, to match eight
      given examples designed to represent varying levels of clinical expertise. The
      informants were asked to consider in what way two of their chosen examples were
      alike and differed from a third in their clinical practice. A total of 55 bi
      polar constructs emerged which were clustered under four main headings. These
      suggested that A & E nurses perceived expert practice to be characterized by a
      high level of empirical knowledge, supportive team building, assertive clinical
      leadership and patient-focused involvement.

PMID- 9528513
TI  - Sudden infant death syndrome (SIDS) on the 'other side'. A personal account and a
      tribute to Dominic Lewis Stead, 21.11.95-22.02.96.
AB  - My own experience of sudden death will remain with me lifelong. I hope that
      whenever I am able to face such a situation again I can give the same expert
      nursing care with such empathy, understanding and compassion that we were shown.
      Because it does matter how we care for the newly bereaved relative, and there is
      ample evidence that the quality of the initial care provided has a major impact
      on the relative's bereavement (RCN British Association for Accident and Emergency
      Medicine 1995).

PMID- 9528514
TI  - Wanted by the police.

PMID- 9528515
TI  - Child abuse and neglect: the knowledge and practice of the A & E nurse.
AB  - The recognition of child abuse depends greatly on the skills of the Accident and
      Emergency (A & E) nurse. A lot of what is written in the relevant literature is
      repetitive. Much is written about what A & E nurses should know and should do,
      but there appears to be no research which examines their actual skills and
      knowledge in this area. This article addresses this and by using a Constructivist
      approach for the inquiry, identifies what a group of A & E nurses know about
      child abuse and what they do when a possible victim presents to the department.
      It identifies some cases which need addressing, particularly knowledge of current
      policies, guidelines and legislation. Also identified are the skills A & E nurses
      possess and those they utilize. The paper concludes that further training and
      education is needed for multidisciplinary decision making about the role of the A
      & E nurse within the context of child abuse and neglect.

PMID- 9528516
TI  - Realizing specialist and advanced nursing practice: a typology of innovative
      nursing roles.
AB  - This paper outlines the findings of the first phase of a Department of Health
      funded project: Realizing Specialist and Advanced Nursing Practice establishing
      the parameters of and identifying competencies for 'Nurse Practitioner' roles and
      evaluating programmes of preparation. An extensive literature review and
      interviews with 49 key informants was used to revise a typology of Domains of
      Innovative Nursing Roles which the authors had constructed. It also emerged from
      the key informant interviews that a substantial number of respondents considered
      the role of the Nurse Practitioner (NP) to be a composite of both specialist and
      advanced practice. Further analysis indicated that although current preparation
      for a 'specialist' role would meet many of the outcomes perceived necessary to
      prepare individuals for the NP role, something 'extra' was seen as a prerequisite
      for the NP. It is suggested, therefore, that there is a strong case for
      considering the NP role in terms of 'specialist plus', and that the typology can
      be helpful in considering the major emphasis within NP roles.

PMID- 9528517
TI  - Terminal fears and panic.
AB  - A terminally-ill patient is being cared for at home by relatives who have no
      medical or nursing experience but who are doing their best and are well supported
      by the holistic care of the community teams. As death becomes imminent, the
      relatives find themselves out of their depth, they panic and dial 999. The
      patient is rushed to Accident & Emergency (A & E) and is possibly dead on arrival
      or shortly afterwards. It is the relatives who now need nursing care, to help
      them through this totally unexpected upheaval. Aspects of this scenario are
      explored in this paper.

PMID- 9528519
TI  - The treatment of drug misusers in police custody.
AB  - Large numbers of drug users appear in police stations, either as a result of drug
      offences or as offenders who also misuse drugs. Invariably such offenders are
      dealt with by police surgeons or forensic medical examiners as they are now
      called. In this paper a review is made of the guidelines for drug users to access
      medical help, and the nature of the medical service provided. Supporting material
      is also provided by the use of some case histories taken from one UK police
      station. An assessment is made of the obligations and requirements of police
      surgeons to notify selected drug users under the Notification Regulations and the
      authors also suggest a more detailed research programme which could be developed.

PMID- 9528520
TI  - I am that agency nurse.

PMID- 9528518
TI  - Paracetamol poisoning.
AB  - Paracetamol is a common cause of fatal self-poisoning in the UK every year.
      Despite this, it continues to be sold freely without medical supervision and can
      be found in quantity in most household medicine cabinets.

PMID- 9528521
TI  - Discharge planning in A & E: part 2.
AB  - Discharge of patients from A & E was considered by both the 1992 and 1996 Audit
      Commission reports. The 1992 Commission recommended that unnecessary return
      attendance for follow-up care should be reduced to a minimum, those requiring to
      make a return visit falling within the range of 10-15% of first attendances.
      Other hospital specialties, GP services and self care were identified as
      appropriate follow-up treatment. This places more emphasis on appropriate
      discharge advice for those who do not need to reattend, and this is an aspect of
      health promotion which largely goes unrecognized. The second part of this study
      explores how effectively A & E departments perform the role of giving appropriate
      discharge advice. Part I of the study, published in October 1997, covered the
      comprehensive discharge planning required for patients who belong to vulnerable
      groups and who commonly reattend.

PMID- 9528522
TI  - Find out about me (quickly).
AB  - Here I am, rushed into your Accident and Emergency department, unconscious but
      not exactly dead. What are you going to do about it? As I write this, ahead of
      time, obviously, we are in Holby (scene of Casualty, for non-TV-watching readers)
      because that is the closest that most members of the general public come to
      knowing about such places.

PMID- 9528523
TI  - Education and the continuing care of older people.

PMID- 9528524
TI  - Functional analysis and occupational standards: their role in curriculum
      development.
AB  - National Vocational Qualifications and national occupational standards have been
      criticized by many academics and professionals, seemingly without a true
      knowledge of the processes and principles that underpin their development. This
      paper attempts to clarify the role that functional analysis and occupational
      standards can play in meeting the demands of central government and purchasers in
      providing educational programmes that meet individual, organizational and
      society's needs. An overview of the processes and principles relating to
      functional analysis and occupational standards is provided, and issues arising
      from their incorporation into professional education programmes are debated.

PMID- 9528525
TI  - Applying theory to practice--the use of 'ripple effect' plans in continuing
      education.
AB  - The difficulties students experience in applying theory to practice are well
      documented and educationalists have employed a variety of techniques in an effort
      to enhance effective application. This paper describes the utilization of one
      such teaching/learning strategy in a diploma level course in management for
      registered nurses and midwives. As problem-solving individual contracts of
      learning, 'ripple effect' plans enabled course participants to apply general
      principles of management theory to specific nursing management practice in their
      everyday world of nursing and midwifery work, making changes in practice and
      procedure which were visible and real.

PMID- 9528526
TI  - Professional knowledge, midwifery and the role of the external examiner.
AB  - Following the move of midwifery education into institutions of higher education
      (IHE), professional sources have voiced some concern over the apparent 'cultural
      conflict' between IHE and the midwives. In order to investigate this, a 1-day
      conference was convened for midwife teachers and external examiners in the south
      of England, during which data were collected from recorded discussions and
      interviews. The findings confirm the existence of conflict which polarized around
      two issues: first, the centrality of practice for midwives and the perceived
      undermining of that practice by the academically orientated IHE; and second, the
      somewhat ambiguous role of the external examiner. These findings are explained in
      terms of recent work on professionalization which suggests that professional
      knowledge can be legitimized where the emphasis is placed on the indeterminate
      elements of the work and where knowledge originates from abstractions and
      conceptualizations derived from working practice. Such a knowledge base would be
      rather more resistant to undermining by the deductive, rationalist approach
      employed by IHE academics. It is suggested that external examiners are best
      placed to represent practice based knowledge to IHE examiners.

PMID- 9528527
TI  - Do school qualifications predict competence in nursing calculations?
AB  - Do entry characteristics in mathematics of student nurses selected to undertake
      nurse training have any predictive value for competence in nursing calculations?
      This paper analyses the results of a diagnostic mathematics test given to
      students entering the Project 2000 course at one college of nursing in England in
      relation to the students' entry qualifications in mathematics. The results
      suggest that paper qualifications in mathematics, other than those of above GCSE
      grade C or equivalent, should not be relied upon to predict performance in a test
      of calculations required in nursing. Selection procedures for nursing courses
      that use a mathematics or numeracy test as a requirement for entry may be
      excluding potentially competent nurses from selection. Opportunities for helping
      to build confidence and competence in nursing calculations should be built into
      the nursing curriculum.

PMID- 9528528
TI  - Implementing a system of structured clinical supervision with a group of
      DipHE(nursing) RMN students.
AB  - Clinical supervision is to become an integral part of mental health nursing, and
      the United Kingdom Central Council for Nursing, Midwifery & Health Visiting has
      recommended that it be incorporated in pre-registration education. This paper
      describes teachers' experiences of delivering a programme of clinical supervision
      education within the mental health branch of a diploma in nursing course. It
      outlines the implementation and evaluation of the programme, including discussion
      of the process and difficulties encountered. The programme appears to have
      provided a positive first experience for the students and to have given them the
      enthusiasm to adopt clinical supervision as part of their future roles as
      qualified practitioners.

PMID- 9528529
TI  - Teaching primary health care: an interdisciplinary approach.
AB  - The growing importance of the development of primary health care services
      necessitates role development for the allied health professions, including
      nursing and radiography. In order to prepare the future professionals to take on
      the challenges brought about by these role developments, educational institutions
      had to include lectures on the principles involved in primary health care
      delivery in the undergraduate curricula of these educational programmes. This was
      done at the University of Malta as an educational experiment, and the students
      were asked to complete a questionnaire about their experiences of pursuing this
      module on an interdisciplinary basis. The most important finding was the fact
      that the majority of respondents indicated that they found the theoretical
      material applicable to professional practice. It also enabled them to work
      towards developing their own roles within a primary health care clinical setting.
      The researchers can therefore suggest that primary health care should be included
      in the curricula of the other health care professions.

PMID- 9528530
TI  - Developing the skills required for evidence-based practice.
AB  - The current health care environment requires practitioners with the skills to
      find and apply the best currently available evidence for effective health care,
      to contribute to the development of evidence-based practice protocols, and to
      evaluate the impact of utilizing validated research findings in practice. Current
      approaches to teaching research are based mainly on gaining skills by
      participation in the research process. Emphasis on the requirement for rigour in
      the process of creating new knowledge is assumed to lead to skill in the process
      of using research information created by others. This article reflects upon the
      requirements for evidence-based practice, and the degree to which current
      approaches to teaching research prepare practitioners who are able to find,
      evaluate and best use currently available research information. The potential for
      using the principles of systematic review as a teaching and learning strategy for
      research is explored, and some of the possible strengths and weakness of this
      approach are highlighted.

PMID- 9528531
TI  - The role of nurse educators in the development of reflective practitioners: a
      selective case study of the Australian and UK experience.
AB  - The potential to improve patient/client care, stimulate the personal and
      professional growth of the practitioner and help close the theory practice gap
      has provoked much discussion in the nursing literature on the benefits of
      reflection on practice. In order to examine recent developments in this area, a
      study tour, supported by the Florence Nightingale Foundation, was conducted in
      Australia and the UK during the spring and summer of 1995. Using an illuminative
      case study approach, data collected demonstrated that although reflective
      practice was fully endorsed by the nursing profession in Australia, and there
      were excellent examples of reflective practice in use, the continued growth of
      the reflective practice movement appeared to be threatened by the rationalization
      of both clinical and theoretical education in the universities. Issues around
      methods of encouraging reflection in students focused on ethical use of journals,
      the levels of reflection developed and the outcome effectiveness of reflective
      learning. Although it is recommended that the nursing profession continue to
      endorse developments in reflective practice in the UK, it is also necessary to
      encourage both process and outcome evaluations of its effects on the development
      of the individual nurse and on the ensuing quality of health care delivery.

PMID- 9528532
TI  - Hearing nurses' voices through reflection in women's studies.
AB  - Women's studies is an elective offered through the Faculty of Nursing and Health
      Sciences, Griffith University-Gold Coast, Australia, and is attended primarily by
      female nursing students. The main objective of this subject is for students to
      gain an improved understanding and application of feminist perspectives. One of
      the teaching/learning strategies we have recently implemented was that of
      reflective processes that allowed us to explore how students' thoughts were
      changed during the course of the subject. As a result of engaging with women's
      studies, students also described how in the future they may incorporate an
      awareness of feminist theories and frameworks into personal and occupational
      roles. This paper describes the common themes identified from this learning
      process and offers a set of empowering stories from female nursing students.

PMID- 9528533
TI  - Issues in nursing education in Nepal.
AB  - Research in Nepal, conducted in 1991-1992, yielded interesting information on
      issues confronting nurse educators in that country. What this author found
      particularly interesting is that, while the specific problems were different, the
      underlying nursing education issues were remarkably similar to those encountered
      by nurse educators in her home country of Canada. Data from questionnaires,
      interviews, and government and other documents have been synthesized in this
      discussion of issues in nursing education in Nepal. Categories for discussion
      include students, faculty, curriculum and institutional constraints.

PMID- 9528534
TI  - Nursing informatics in nursing education: a challenge to nurse teachers.
AB  - The use of computers in education has become commonplace. In this study with 162
      nurse teachers, we found that although most nursing colleges in Finland have the
      necessary hardware for teaching informatics, teachers are not familiar with the
      software that is available for nursing education purposes. Teachers also lack
      confidence in their own abilities to cope with computer-assisted education. The
      information systems used in practical nursing are often inaccessible to nurse
      teachers. The teachers themselves say they would regularly need further training
      in their own computer skills.

PMID- 9528536
TI  - Tired of waiting.

PMID- 9528535
TI  - The big issue.

PMID- 9528537
TI  - Speak for yourself.

PMID- 9528538
TI  - Action stations.

PMID- 9528539
TI  - Home base.

PMID- 9528540
TI  - Facing the future.

PMID- 9528541
TI  - Your views on nurse regulation.

PMID- 9528542
TI  - Universal precautions.

PMID- 9528543
TI  - Blood pressure measurement: assessing staff knowledge.

PMID- 9528544
TI  - Managing risk factors for hypertension in primary care.

PMID- 9528545
TI  - Commissioning nurse education.

PMID- 9528546
TI  - Diabetes: reflecting on empowerment.

PMID- 9528547
TI  - Putting it on the record.

PMID- 9528548
TI  - Breaking down boundaries.

PMID- 9528549
TI  - Ticking bomb.

PMID- 9528550
TI  - Seeing is believing.

PMID- 9528551
TI  - The poverty trap.

PMID- 9528552
TI  - Healthy diet helps healing.

PMID- 9528553
TI  - Regulation review--name games.

PMID- 9528554
TI  - Nursing Standard's Nurse 98 Award. Making the most of a special year.

PMID- 9528555
TI  - Parkinson's disease and the role of nurse specialists.

PMID- 9528556
TI  - Change theory and health promotion.

PMID- 9528557
TI  - Risk factors for hypertension and cardiovascular disease.

PMID- 9528559
TI  - Parkinson's disease.

PMID- 9528558
TI  - Assessment and measurement of competence in practice.

PMID- 9528560
TI  - Trick or treatment.

PMID- 9528561
TI  - No one's a winner.

PMID- 9528562
TI  - Where nurses stand sentinel.

PMID- 9528563
TI  - Capital gains.

PMID- 9528564
TI  - Sometimes a touch is enough.

PMID- 9528565
TI  - Our meagre pay award.

PMID- 9528566
TI  - Emotional healing.

PMID- 9528567
TI  - Being a nurse is not what I do, it's what I am.

PMID- 9528568
TI  - The secret ingredient.

PMID- 9528569
TI  - Continence assessment.

PMID- 9528570
TI  - Nursing abroad--culture clubbed.

PMID- 9528571
TI  - Viruses--little monsters.

PMID- 9528572
TI  - Primary care--survival tactics.

PMID- 9528574
TI  - Infant hearing tests.

PMID- 9528573
TI  - Marfan's syndrome--defusing a time bomb.

PMID- 9528575
TI  - Bacterial vaginosis.

PMID- 9528576
TI  - The humanistic therapies.

PMID- 9528577
TI  - The humanistic therapies. Case study: coping with chaos.

PMID- 9528578
TI  - Nursing on the European map.
AB  - There is little good data on the state of nursing in Europe. The World Health
      Organization has therefore compiled nursing and midwifery profiles of most of its
      50 European member states, and used them to analyse the current situation, spot
      trends, enable meaningful comparisons and stimulate development. The author, who
      launched this project while working as regional adviser for nursing and midwifery
      in WHO's European regional office from 1991-95, describes how the profiles were
      compiled and uses nursing leadership in Europe as a case study to illustrate the
      type of information and analysis contained in the study.

PMID- 9528579
TI  - Continence--targets and rewards.

PMID- 9528581
TI  - Continence--it's never too late.

PMID- 9528580
TI  - Continence--lessons in control.

PMID- 9528583
TI  - [Drugs cost double the amount for physicians].

PMID- 9528582
TI  - Continence--who's paying?

PMID- 9528584
TI  - [A gentle stream of new and expensive drugs].

PMID- 9528585
TI  - [300 million kroner for advertising].

PMID- 9528586
TI  - [Nerve drugs for 2 billion].

PMID- 9528587
TI  - [Preparations with the new medicine].

PMID- 9528588
TI  - [Blue-frozen preparedness].

PMID- 9528589
TI  - [Large differences in counties' disaster preparedness].

PMID- 9528590
TI  - [Ugeskrift for Laeger criticizes disaster preparedness].

PMID- 9528591
TI  - [Every third hip fracture can be prevented].

PMID- 9528592
TI  - [Osteoporosis--when medical treatment is necessary].

PMID- 9528593
TI  - [Illegal trade in organs].

PMID- 9528594
TI  - [Nurse missing].

PMID- 9528595
TI  - [Mercy killing moves Spanish attitude on dying].

PMID- 9528596
TI  - [Fyn's preparation for new wages].

PMID- 9528597
TI  - [Poor chemistry].

PMID- 9528598
TI  - [Nursing. A professional foundation].

PMID- 9528599
TI  - [After ship's accident--physician on duty made wrong decision about ambulance].

PMID- 9528600
TI  - [Heart arrest--when seconds count. Interview by Grethe Kjaergaard].

PMID- 9528601
TI  - [Heart arrest--timely effort saves lives].

PMID- 9528602
TI  - [Strategy for improving of advertisements for nursing teachers].

PMID- 9528603
TI  - [Executive Board--new recipe for ombudsmen].

PMID- 9528604
TI  - [Executive Board--countdown to 1999 negotiations].

PMID- 9528605
TI  - [Peace for television time].

PMID- 9528607
TI  - [Education--much needed discussion].

PMID- 9528606
TI  - [Nursing--vomiting in young children with multiple handicaps].

PMID- 9528608
TI  - [Education--current demands of role as examiner].

PMID- 9528609
TI  - [History--inquiry for old hospital emblems].

PMID- 9528610
TI  - [New wage forms--wage earners want clarification].

PMID- 9528611
TI  - [Following heart arrest--aid to the helpers. Interview by Grethe Kjaergaard].

PMID- 9528612
TI  - [Reduced working capacity is no obstacle].

PMID- 9528613
TI  - [Balance for a dignified life].

PMID- 9528615
TI  - [Improved safeguarding of rights for health personnel].

PMID- 9528614
TI  - [The difficult talk. Interview by Mette Willumsen].

PMID- 9528616
TI  - [Many nurses' cases].

PMID- 9528617
TI  - [Name plates are communication].

PMID- 9528618
TI  - [Male authority].

PMID- 9528619
TI  - [Nursing--Agnethe Jensen's final time].

PMID- 9528620
TI  - [Ulcer treatment in home nursing].

PMID- 9528621
TI  - ["We have lowered our demands to be able to stand up". Interview by Anne Sorman
      Forsby].

PMID- 9528622
TI  - ["Why do we really stay?"].

PMID- 9528623
TI  - [Political polarization--hot debate on nursing and marketing].

PMID- 9528624
TI  - ["I understand that members are angry". Interview by Jan Thomasson].

PMID- 9528625
TI  - [Care of the aged--medically accountable nurses should clean up in community
      care].

PMID- 9528626
TI  - ["Dangerous" curiosity can have dividends].

PMID- 9528627
TI  - [Health care financing--capital steering never safeguards the weak in society].

PMID- 9528628
TI  - [Health care financing--no member majority in privatization of care].

PMID- 9528629
TI  - [In an ambulance one is an ambulance-nurse].

PMID- 9528630
TI  - [Dialogue better than confrontation in staffing of ambulances].

PMID- 9528631
TI  - [Daring to put out feelers].

PMID- 9528632
TI  - [We should talk about existential question. Interview by Elisabet Forslind].

PMID- 9528633
TI  - [Anitha is healthy!. Interview by Inger Jalakas].

PMID- 9528634
TI  - [Physician is chief of nursing education].

PMID- 9528635
TI  - [Bacteria outwit us].

PMID- 9528636
TI  - [New thinking results in new antibiotics].

PMID- 9528637
TI  - [Children with asthma and allergies--supportive communication helps families to
      ameliorate stress].

PMID- 9528638
TI  - [Children with asthma and allergies--allergy consultants increase understanding
      of allergic children].

PMID- 9528639
TI  - [Education in care of dementia--educated personnel gives better care to
      handicapped dementia patients].

PMID- 9528640
TI  - ["Problems are there to be solved". Interview by Mats Nihlen].

PMID- 9528641
TI  - [When the EU pays everybody makes decisions. Interview by Anders Olsson].

PMID- 9528642
TI  - [Farewell to free negotiation rights. Collective salaried employees' movement
      protests against committee proposal].

PMID- 9528643
TI  - [The treatment of AIDS too expensive?].

PMID- 9528644
TI  - [How effective is spa treatment? A systematic review of randomized studies].
AB  - BACKGROUND AND OBJECTIVE: In the context of general financial constraints within
      many national health services spa treatment is being looked at ever more
      critically in various European countries. An important argument against spa
      treatment has been the supposed lack of evidence for its efficacy. This analysis
      was undertaken to gather firm data bearing on this problem. METHODS: Several data
      bases were searched systematically for randomized studies of spa treatment. Only
      those were included in which one patient cohort had received spa treatment, while
      the control cohort had been treated for the same ailment on an ambulant basis at
      home. Nonrandomized studies were excluded. RESULTS: Only three randomized studies
      were found in which two patient cohorts, one with and one without spa treatment,
      were compared (postsalpingitis, back pain and osteoarthritis, respectively). In
      all three the evidence indicated some additional benefit from spa treatment.
      CONCLUSIONS: The data are not sufficient to prove the benefit of spa treatment,
      nor are they adequate to disprove it. More evidence-based studies are necessary
      to arrive at rationally based decisions relating to the efficacy of spa
      treatment.

PMID- 9528645
TI  - [Autoimmune encephalopathy in Hashimoto's thyroiditis. A differential diagnosis
      in progressive dementia syndrome].
AB  - HISTORY AND CLINICAL FINDINGS: A 58-year-old woman, known for 10 years to have
      Hashimoto's thyroiditis, was admitted from another hospital where, after an
      initial period of unconsciousness, she had developed progressive severe dementia,
      abnormal arousal and generalized myoclonia. Jakob-Creutzfeldt disease (JCD) was
      suspected. INVESTIGATIONS: The electroencephalogram (EEG) showed marked slowing
      of the basic activity and episodes of triphasic waves. The titres of thyroid
      antibodies (TPO 764 kU/l, TgAk 398 kU/l) and of the antinuclear antibodies (ANA
      1:1280) were raised, as was the erythrocyte sedimentation rate (80/120 mm and the
      cerebrospinal fluid albumin concentration (1 g/l). TREATMENT AND COURSE: The
      history and findings suggested autoimmune encephalitis (AIE) and treatment with
      prednisolone, 2 mg/kg body weight daily, was initiated, achieving lasting
      improvement of arousal within two days. 6 weeks later the EEG merely showed mild
      alteration of basic activity. The thyroid antibody titres were now within normal
      limits and the signs of inflammation were regressing. CONCLUSION: In case of
      rapidly progressive dementia autoimmune antibodies should be looked for in the
      differential diagnosis, because autoimmune disease may be the treatable cause.

PMID- 9528646
TI  - [Pyostomatitis vegetans and Crohn's disease. A specific association of 2
      diseases].
AB  - HISTORY AND CLINICAL FINDINGS: A 27-year-old man was referred to the
      dermatological out-patient clinic because of inflammatory changes in the oral
      mucosa of unknown cause. 5 months earlier he had been diagnosed as having Crohn's
      disease of the terminal ileum. On both sides of the buccal mucosa there were
      rough erythematous vegetations and disseminated miliary abscesses, which extended
      to the labial gingiva and the soft palate. Further physical examination was
      unremarkable. INVESTIGATIONS: Several inflammatory parameters were increased: C
      reactive protein 100 mg/l, erythrocyte sedimentation rate 55/88 mm, eosinophilic
      cationic protein 35.8 ng/ml (normal range 2.3-16 ng/ml). White cell count was
      normal (7,25/nl), with a lymphocytopenia of 11.9%. There was no eosinophilia.
      Haemoglobin was reduced to 11.6 g/dl and the platelets raised to 526/nl. Smears
      of the oral mucosa showed no fungal, viral or bacterial infection. Biopsy
      revealed leucocytic microabscesses in the epithelium, granulation tissue and flat
      ulcerations with adjoining superficial necrotic zones. DIAGNOSIS, TREATMENT AND
      COURSE: The clinical and histological picture as well as the association with
      Crohn's disease (CD) suggested pyostomatitis vegetans (PV). The PV was treated
      with disinfectant mouth washes which improved the subjective findings. Budesonide
      was given for CD. CONCLUSION: PV is a rare and usually isolated condition, but it
      can also occur in association with a chronic gastrointestinal disease such as
      ulcerative colitis and Crohn's disease. The diagnosis of PV indicates a thorough
      gastroenterological investigation.

PMID- 9528647
TI  - [The current diagnosis of primary sclerosing cholangitis].

PMID- 9528648
TI  - [Urticaria pigmentosa and mastocytosis].

PMID- 9528649
TI  - [Procalcitonin and bacterial infections].

PMID- 9528650
TI  - [A transnasally placed percutaneous endoscopic gastrostomy probe].

PMID- 9528651
TI  - Postmortem stability of total RNA isolated from rabbit ligament, tendon and
      cartilage.
AB  - The stability of RNA, particularly mRNA, in tissues is under complex regulation.
      Most studies to date have focused on very cellular tissues and not connective
      tissues such as ligaments, tendons and cartilage. As the availability of such
      tissues for transplantation or research purposes is frequently delayed following
      death, it is important to determine whether RNA stability in such tissues is
      influenced by time postmortem. To approach this question, skeletally mature NZW
      rabbits were used to investigate RNA integrity over time in dense, hypocellular
      connective tissues and in several hypercellular organ tissues such as brain,
      kidney, liver and lung. Samples were analyzed at varying intervals postmortem
      with respect to rRNA integrity by agarose gel electrophoresis and ethidium
      bromide staining and mRNA integrity by Northern blot analysis and RT-PCR. No
      degradation of rRNA or loss in integrity of mRNA for genes of low and high copy
      number was observed up to 96 h postmortem. These findings confirm that it is
      likely appropriate to use properly stored postmortem dense connective tissues for
      molecular biological investigations.

PMID- 9528652
TI  - In situ visualization of messenger RNA for basic fibroblast growth factor in
      living cells.
AB  - We examined whether messenger RNA for basic fibroblast growth factor (bFGF) could
      be visualized specifically by a fluorescent probe in living cells. A 15
      nucleotide-long antisense or sense sequence for human bFGF was sandwiched between
      two complementary 5-nucleotide-long arm sequences. A fluorophore, 5-(2'
      aminoethyl)aminonaphthalene-1-sulfonic acid (EDANS), was joined to the 5'
      terminal phosphate, while 4-(4'-dimethylaminophenylazo)benzoic acid, quencher for
      EDANS, was joined to the 3'-terminal hydroxyl group. The probe emitted blue
      fluorescence only upon hybridization with the complementary 18-nucleotide-long
      sequence under ultraviolet light. The antisense or sense probe carried with
      liposome was delivered to human cells, trabecular cells of the eye, in a glass
      bottom culture dish placed on the stage of an inverted microscope. Cells with the
      antisense probe did, but not with the sense probe, show blue fluorescence under
      ultraviolet light. The present study opens a way to measure the changing levels
      of a specific messenger RNA in living cells.

PMID- 9528653
TI  - Extracellular volume in streptococcal model biofilms: effects of pH, calcium and
      fluoride.
AB  - Diffusion, which limits nutrient penetration and end-product export in biofilms,
      is restricted by reversible binding and extracellular volume fraction (Ve).
      Fluoride has been demonstrated to prevent calcium bridging, hence inhibiting
      calcium-mediated cell association (Rose, Lee and Shellis, Caries Res. 30 (1996)
      458-464). 3H-inulin effusion measurements from streptococcal model plaques, at pH
      7.0 or 5.0, 0-20 mmol/l Ca2+, and with or without 5 mmol/l KF, demonstrated that
      Ve was greatest in the absence of added Ca2+ and at pH 7.0, lowest at 20 mmol/l
      Ca2+ and pH 5.0, and that F- raised the minimum Ve. By bridging adjacent cells
      and reducing the net negative charge, calcium and low pH, respectively, reduce
      Ve. Fluoride eliminates the calcium-bridging effect, hence increasing Ve.

PMID- 9528654
TI  - Partition coefficients of alpha-amylase in aqueous two-phase systems PEG +
      MgSO4.7H2O + H2O at 298 K.
AB  - Partition coefficients of alpha-amylase have been determined in a polyethylene
      glycol (average molecular mass 8000)/MgSO4.7H2O aqueous two-phase system at 298 K
      and the influence of polymer, salt and initial enzyme concentration on partition
      was investigated. Correlations are proposed which relates the partition
      coefficient to the initial enzyme concentration and the concentration difference
      between phases of polymer and salt. The free volume change, related to the
      densities of the separate phases, has a direct dependence with such polymer and
      salt concentration differences, respectively, and is then used to facilitate
      future estimations. Thus, the partition coefficient is a function of this
      physical parameter and the initial enzyme concentration employed (1.25, 2.50 and
      5.00 g dm-3).

PMID- 9528655
TI  - Purification and preliminary characterisation of praelongin phospholipases,
      antiplatelet agents from the snake venom of Acanthophis praelongus.
AB  - Three praelongin phospholipases were chromatographically purified from the snake
      venom of Acanthophis praelongus. The purity and homogeneity of the praelongins
      were assessed by RP-HPLC, HPCE and mass spectrometry. The purified enzymes,
      praelongins 2bIII, 2cII and 2cIV were found to have phospholipase A2 activities
      with specific activities of 31.4 +/- 0.4, 326.1 +/- 10.2 and 362.5 +/- 12.0 U/mg,
      respectively. Mass spectrometry studies showed the molecular mass of praelongin
      2bIII to be 12,782.9 +/- 2.6 and praelongins 2cII and 2cIV to have very similar
      molecular mass values, 12,971.4 +/- 4.5 and 12,971.9 +/- 3.6, respectively.
      However, platelet aggregation studies showed the praelongins to display different
      IC50 values, 180 microM for praelongin 2cII and 55 microM for praelongin 2cIV;
      praelongin 2bIII was found to be a more potent antiplatelet agent, having an IC50
      of 0.65 microM. Praelongins 2bIII, 2cIV and 2cII were found to have pI values of
      10.3 +/- 0.3, 9.6 +/- 0.6 and 9.4 +/- 0.6 as determined by HPCE. The antiplatelet
      potencies do not correspond to their in vitro phospholipase catalytic potencies,
      but appear to be related to the enzyme isoelectric points.

PMID- 9528656
TI  - Legume vicilins (7S storage globulins) inhibit yeast growth and glucose
      stimulated acidification of the medium by yeast cells.
AB  - Vicilin (7S storage proteins) isolated from different legume seeds were shown to
      inhibit yeast growth and glucose stimulated acidification of the medium by yeast
      cells. The degree of growth inhibition varied with the origin of vicilins. It was
      more than 90% for vicilins from cowpea (Vigna unguiculata, cultivar pitiuba) and
      equal to 65% for vicilins from Vigna radiata, in the case of Saccharomyces
      cerevisae. Vicilins from cowpea seeds inhibited the glucose stimulated
      acidification of the medium by S. cerevisae up to 60%. We have also observed that
      vicilins bind to yeast cells. We suggest that vicilins bind to chitin-containing
      structures of yeast cells and that such association could result in inhibition of
      H+ pumping, cell growth and spore formation. A final consequence of the yeast
      growth inhibition by vicilins is (probably) the formation of spores.

PMID- 9528657
TI  - Site-specific cleavage of tRNA by imidazole and/or primary amine groups bound at
      the 5'-end of oligodeoxyribonucleotides.
AB  - Sequence specific RNA cleaving molecules were synthesized by attaching novel
      polyamine derivatives bearing imidazole and/or primary amine groups to the 5'-end
      of DNA oligonucleotides as the sequence-recognizing moieties. The actions of the
      molecules on a half-tRNA(Asp) were investigated. The oligonucleotides directed
      the nuclease activity (the imidazole and the primary amine are the catalytic
      groups) of the enzyme to the nucleotides directly adjacent to the complementary
      target sequence on the substrate RNA. The cleavage reaction shows a bell-shaped
      pH dependence with a maximum at pH 7.0, indicating the participation of
      protonated and non-protonated imidazoles residues in the process. The specificity
      of these hybrid enzymes can be easily altered, and they should prove to be useful
      tools for probing RNA structures in solution and as potential reactive groups in
      antisense oligonucleotide derivatives. We also describe the site-specific
      cleavage of tRNA(Asp) by the cleaving reagents bearing imidazole and/or primary
      amine groups at the 5'-end of oligodeoxyribonucleotides.

PMID- 9528658
TI  - 1H-nuclear magnetic resonance evidence for acto-myosin-dependent structural
      changes of the intracellular water of frog skeletal muscle fiber.
AB  - The proton-spin relaxation process of the intracellular water in intact-relaxed
      and skinned-rigor fibers of frog skeletal muscle was studied for slack and
      stretched fibers by use of 1H-nuclear magnetic resonance technique. The
      longitudinal and transverse proton-spin relaxation processes of the intracellular
      water of intact-relaxed and skinned-rigor fibers were composed of a single- and
      multi-exponential processes, respectively. The longitudinal relaxation process
      was almost the same in slack as well as in stretched fibers for both intact
      relaxed and skinned-rigor fibers. On the other hand, the transverse relaxation
      process was slightly but significantly faster in stretched than in slack fibers
      in the case of skinned-rigor fibers while it was almost the same in slack and in
      stretched fibers in the case of intact-relaxed fibers. As the overlap between
      actin and myosin filaments is maximal in slack fibers and minimal in stretched
      fibers, these results indicate that the intracellular water located in the
      overlap region is less structured in rigor fibers than that in relaxed fibers.
      This suggests that the rigor crossbridge formation disrupts the structured water
      bound to myosin and actin filaments in muscle fiber.

PMID- 9528659
TI  - The mode of action of allicin: trapping of radicals and interaction with thiol
      containing proteins.
AB  - Allicin (thio-2-propene-1-sulfinic acid S-allyl ester) is the main biologically
      active component of garlic clove extracts. Its biological activity was attributed
      to either antioxidant activity or thiol disulfide exchange. Antioxidant
      properties of both allicin and its precursor, alliin (+S-allyl-L-cysteine
      sulfoxide), were investigated in the Fenton oxygen-radical generating system
      [H2O2-Fe(II)]. Using the spin trapping technique and ESR, it was found that both
      compounds possessed significant antioxidant activity. The reaction between
      allicin and L-cysteine was studied by 1H and 13C-NMR, and a S-thiolation product,
      S-allylmercaptocysteine, was identified. Allicin irreversibly inhibited SH
      protease papain, NADP(+)-dependent alcohol dehydrogenase from Thermoanaerobium
      brockii (TBAD), and the NAD(+)-dependent alcohol dehydrogenase from horse liver
      (HLAD). All the three enzymes could be reactivated with thiol containing
      compounds. Papain could be reactivated with glutathione, TBAD with dithiothreitol
      or 2-mercaptoethanol (2-ME) but not by glutathione, while HLAD could be
      reactivated only with 2-ME. This study demonstrates that in addition to its
      antioxidant activity, the major biological effect of allicin should be attributed
      to its rapid reaction with thiol containing proteins.

PMID- 9528660
TI  - Regulation of acid trehalase activity by association-dissociation in
      Saccharomyces cerevisiae.
AB  - Acid trehalase (AT) has always been reported to be copurified with invertase (I)
      and a 40 kDa additional protein. Glucose grown stationary phase cells of
      Saccharomyces cerevisiae contained least I activity. So, it was attempted to
      purify AT from these cells (I:AT = 10.83). Studies on specific activity, percent
      recovery and I:AT ratio of different pools, collected during purification of AT,
      indicated that samples containing ratio I:AT < 2.2 were unstable. Purification
      methodology favouring association (DEAE-Sephadex chromatography) resulted in
      gaining total activity while methodology favouring dissociation (HPGPLC) resulted
      in tremendous loss in recovery. Active pool (Pool 1X) appeared to be
      electrophoretically homogeneous but dissociated into 175, 90, 68, 61, 57 (minor
      bands) and 37-41 (major band) molar mass (kDa) bands on SDS-PAGE. Inactive pools
      (Pools 1Y, 3X, 3Y) did not contain the 37-41 kDa major band. So, association of
      both I and a 37-41 kDa protein with AT appeared to be essential. Two bands of
      isoelectric pH (pI) 4.6 and 4.7 were present in pool 1X enzyme preparation. All
      SDS-PAGE-resolved bands of pool 1X, in an average, contained high
      aspartate/asparagine and low cysteine residues. AT activity appeared to be highly
      sensitive to the change in pH and also to agents affecting ionisation of protein,
      e.g., betaine, NaCl, acetate, etc. Association of AT components in presence of
      NaCl was demonstrated spectrophotometrically. Specific activity of AT decreased
      with dilution. Substrate mediated allosterism for this enzyme preparation
      suggested that AT existed as an equilibrium mixture of protomer-oligomer. It was
      suggested that reversible association-dissociation was a mechanism for the
      regulation of AT activity.

PMID- 9528661
TI  - Bicarbonate promotes a cleavage of lactone ring of dehydroascorbate.
AB  - The half-life of dehydroascorbate (DHA) in human plasma is only a few minutes.
      This DHA disappearance is caused by a cleavage of lactone ring. Similarly, when
      DHA was incubated in Dulbecco's modified Eagle's medium (D-MEM), which stood in
      atmosphere of 5% CO2-95% air, the rapid transformation of DHA into 2,3
      diketogulonate (2,3-DKG) is also observed. These observations suggest that both
      human plasma and D-MEM contain a common component, which promotes the hydrolysis
      of DHA. In the present study, this component was identified to be bicarbonate
      which acts as a general base catalyst. Direct evidence for this mechanism was
      obtained as follows: (1) significant hydrolysis of DHA in the bicarbonate-free D
      MEM (pH 7.40) was not observed; (2) hydrolysis of DHA in Tris-HCl buffer at
      constant pH (7.4) increases with increasing bicarbonate concentration; and (3)
      significant hydrolysis of DHA in the decarbonated ultrafiltrate of plasma was not
      observed. These results suggest that DHA hydrolysis may be controlled by the
      variation of CO2 pressure in circulating blood.

PMID- 9528662
TI  - Extracellular ribonuclease from Rhizopus stolonifer: characteristics of an
      atypical--guanylic acid preferential--enzyme from ribonuclease T2 family.
AB  - An extracellular ribonuclease from Rhizopus stolonifer (designated as RNase Rs)
      was purified to homogeneity by chromatography on DEAE-cellulose followed by CM
      cellulose. The Mr of the purified enzyme determined by gel filtration and SDS
      PAGE is 25,000 and 28,200, respectively. RNase Rs is a glycoprotein and contains
      10.5% neutral sugar. It is an acidic protein with a pI of 5.0 and has a blocked N
      terminus. The optimum pH and temperature are 5.5 and 45 degrees C, respectively.
      RNase Rs shows high stability between pH 6.0-10.0. Divalent cations like Zn2+,
      Hg2+ and Cu2+ inhibit the enzyme activity whereas, mononucleotides does not have
      any significant effect. The enzyme cleaves RNA to 3'-mononucleotides via 2',3'
      cyclic nucleotides, with preferential liberation of 2',3'-cyclic GMP, suggesting
      that RNase Rs is a guanylic acid preferential cyclizing RNase. Moreover, cyclic
      nucleotides generated are highly resistant to further hydrolysis.

PMID- 9528663
TI  - Epitope mapping and serodiagnosis using Ata- and (Lys)7 peptides.
AB  - The general applicability of the new peptide immobilization strategy in which the
      peptide of interest is N-terminally extended with an acetyl-thio-acetyl group or
      (poly)-Lys extension during synthesis, has been demonstrated in epitope-mapping
      experiments and serodiagnosis. Ala-scanning experiments and minimal epitope
      determination showed that the antigenicity of Ata-extended peptides derived from
      the human chorionic gonadotropin (hCG) and hepatitis B virus (HBV) amino acid
      sequence, was superior to the free parent peptides. Further, it could be shown
      that the choice of the epitope-mapping procedure (peptide in solution or
      immobilized on a solid support) may lead to a different perception of which
      residues constitute the epitope. In addition, a time-consuming conjugation
      process could be circumvented since the ELISA reactivity of BSA-conjugates was
      comparable to that of Ata-extended peptides. In the serodiagnosis using sera from
      various HIV-positive individuals, the lysyl-peptide showed a signal/noise ratio
      10 times higher than the parent peptide, indicating that sensitivity increased as
      a result of this N-terminal lysyl tail. In all experiments we observed that
      antibody detection could be performed at roughly 10 times lower amounts of
      peptide when N-terminally linked to an Ata-group or lysyl-extension compared to
      the free parent peptide or the BSA-conjugated equivalent.

PMID- 9528664
TI  - Molecular structural changes in human fetal tissue during the early stages of
      embryogenesis.
AB  - Low-angle synchrotron X-ray diffraction studies of human fetal extensor tendon
      and skin collagen, centred in time about the period of first major movement by
      the fetus, indicate that alignment of the tendon collagen fibrils occurs about
      this time. At this stage there appears to be no detectable structural difference
      between tendon and dermis. By three weeks post-partum, marked differences between
      these tissues can be detected. The distribution of the intermediate filament
      diameters for all fetal tendons investigated was unimodal (mean 41.2 +/- 0.4 nm)
      in contrast with that for post-partum tendon which is multimodal. Equatorial
      periodicities of 353 +/- 3 nm and 32.1 +/- 0.1 nm, consistent with the presence
      of type IV collagen, were obtained from all fetal samples examined. Neither of
      these periodicities were observed in post-partum normal tendon and only the
      larger were observed in post-partum normal skin. The consistency of the results
      suggest that low-angle X-ray diffraction could be used for the identification of
      fetal-like tissues found in pathological tissues.

PMID- 9528665
TI  - Effect of folic acid on thymidylate synthase and thymidine kinase in regenerating
      rat liver after partial hepatectomy.
AB  - The effects of folic acid on liver regeneration after partial hepatectomy were
      investigated. The injection of folic acid inhibited the increases in the
      activities of thymidylate synthase and thymidine kinase in regenerating rat liver
      at 24 h after partial hepatectomy, with a concomitant reduction in DNA content.
      Northern blot analysis showed that this inhibition was due to the delay of the
      elevation of the mRNA levels of thymidylate synthase and thymidine kinase after
      partial hepatectomy. At 48 and 72 h, after partial hepatectomy, the thymidylate
      synthase activities in the folic acid injected rats increased to about 1.9- and
      1.7-fold the corresponding control level, respectively, while thymidine kinase
      activities were similar to the control. Immunoblotting assay indicated that the
      increases in the thymidylate synthase activity at 48 and 72 h after partial
      hepatectomy were caused by a three fold increase in its protein level. Folic acid
      suppressed chymotryptic hydrolysis of thymidylate synthase. These suggest that
      folic acid increases the protein level of thymidylate synthase, at least in part,
      through protection against proteolysis.

PMID- 9528666
TI  - Small angle neutron scattering analysis of thermal stability of 23S rRNA and the
      intact 50S subunits of Sulfolobus solfataricus.
AB  - The ribosomes of the extremely thermophilic archaebacterium, Sulfolobus
      solfataricus, are very resistant to thermal denaturation (optimal growth
      temperature 87 degrees C), remaining essentially intact up to above 90 degrees C.
      However, the separate ribosomal components (rRNA and r-proteins) are less
      thermally stable than the ribosome as a whole, indicating that the mode of
      interaction of all of the components within the ribonucleoprotein particle play
      an essential role in determining thermal stability. To get some insight into the
      structural features of the thermophilic ribosome, we performed small angle
      neutron scattering (SANS) measurements at various temperatures on Sulfolobus
      solfataricus intact large ribosomal subunits (50S) and deproteinated large
      ribosomal subunit RNA (23S). Even if the scattering profiles suggest the presence
      of supramolecular aggregates in all of the samples and at all of the investigated
      temperatures, the measured form factors indicated for both samples that, at
      temperatures above 70 degrees C, the suspended particles underwent a structural
      rearrangement. This finding is likely to reflect single particles' properties,
      since S. solfataricus ribosomes are known to be biologically activated only above
      60 degrees C, and there are indications that such activation requires a
      conformational rearrangement of the particle. A remarkable superimposition of the
      percentage variation of the volume from neutron scattering and of the absorbency
      increment with respect to temperature supports this view.

PMID- 9528667
TI  - Molecular cloning and functional expression of a rabbit renal organic cation
      transporter.
AB  - A cDNA encoding an organic cation transporter (rbOCT1) was isolated from rabbit
      kidney. The cDNA encodes a 554 amino acid protein that is highly homologous to
      other mammalian organic cation transporters. rbOCT1 mediated 3H-1-methyl-4
      phenylpyridinium (3H-MPP+) transport in Xenopus laevis oocytes was saturable,
      sensitive to membrane potential, and inhibited by various organic cations. rbOCT1
      mRNA transcripts are expressed in the kidney, liver, and intestine.

PMID- 9528668
TI  - Cloning of AtMRP1, an Arabidopsis thaliana cDNA encoding a homologue of the
      mammalian multidrug resistance-associated protein.
AB  - A cDNA encoding a putative ATP-binding cassette (ABC) transporter from
      Arabidopsis was cloned and sequenced based on an EST clone homologous to ABC
      sequences in other species. The cDNA is 5.5 kb long and contains an ORF encoding
      a 1623 amino acids protein. This sequence is the first MRP-like protein found in
      plants.

PMID- 9528669
TI  - Cloning and expression of an insect Ca(2+)-ATPase from Heliothis virescens.
AB  - A complementary DNA for the Tobacco Budworm, Heliothis virescens,
      sarco(endo)plasmic reticulum-type Ca(2+)-ATPase (HVSERCA) has been cloned and
      sequenced. cDNA fragments of adult rabbit fast-twitch muscle Ca(2+)-ATPase
      (SERCA1a) were used as heterologous probes to isolate a partial cDNA clone coding
      for a protein with high homology to the Ca(2+)-ATPase from Drosophila
      melanogaster (DRSERCA) and vertebrate ER/SR Ca2+ pumps. The entire cDNA clone
      contains an ORF encoding a protein of 1000 amino acids which shares the
      characteristic motifs of a P-type ATPase. HVSERCA shares 89% identity with
      DRSERCA, 80% identity with the Artemia Ca(2+)-ATPase and 72% identity with avian
      and mammalian SERCAs. An insect Ca(2+)-ATPase-specific polyclonal antiserum has
      been raised against a fusion protein containing sequence from the cytoplasmic
      domain of HVSERCA. Heterologous expression of the insect pump in COS-7 cells has
      been demonstrated by immunocytochemistry and the reticular pattern of staining is
      consistent with an ER localisation. However, the expressed enzyme from COS-7
      cells does not appear to be active.

PMID- 9528670
TI  - DMSO produces a new subgel phase in DPPC: DSC and X-ray diffraction study.
AB  - Equilibrium phases and the kinetics of subgel phase transformation of
      dipalmitoylphosphatidylcholine (DPPC) hydrated with mixtures of dimethylsulfoxide
      (DMSO)/water have been studied using differential scanning calorimetry (DSC) and
      X-ray diffraction (XRD). The rate of gel-to-subgel transformation is decreased
      with a small increase in X, the DMSO/water mole fraction, but then speeds up and
      becomes faster than in pure water by X = 0.16. The DSC scans show multiple subgel
      peaks, some of which can be attributed to impacted domain growth. For X greater
      than 0.10, XRD shows that there is a new, stable subgel phase, S, which also
      accounts for some of the multiplicity of DSC peaks. Our electron density profiles
      show that the thickness of the bilayer in the S phase is greater than in the
      usual C subgel phase. We suggest that the S subgel phase is characterized by
      different headgroup ordering and smaller chain tilt angle than in the C subgel
      phase. Electron density profiles show that increasing X decreases the water space
      between bilayers in all phases, subgel, gel and fluid (L alpha). For X = 0.20, a
      different gel phase is also observed that may be due to subtle changes in the
      orientation of chain tilt first observed in partially dehydrated DMPC. The
      dehydrating effect of DMSO explains the results of a previous study, confirmed in
      this study, that increasing the concentration of DMSO raises the main transition
      temperature and eliminates the ripple phase.

PMID- 9528671
TI  - The structure of DNA complexes with cationic liposomes-cylindrical or flat
      bilayers?
AB  - DNA complexes with cationic lipids promise to be versatile and effective
      synthetic transfection agents. Recent experiments identified both flat lamellar
      structures, where DNA strands are sandwiched between lipid bilayers, and
      cylindrical ones where the DNA is coated by a curved bilayer. Using a simple
      model we compare the stability of the two structures, and find that flat-bilayer
      aggregates are always more stable than the cylindrical ones. The different
      experimental observations are explained within the framework of the model
      predictions.

PMID- 9528672
TI  - Characterization of a pH-sensitive surfactant, dodecyl-2-(1'-imidazolyl)
      propionate (DIP), and preliminary studies in liposome mediated gene transfer.
AB  - The inefficiency of non-viral gene delivery systems, relative to viral systems,
      is likely due, in part, to the failure of endosomes to release DNA before
      reaching degradative lysosomes. A solution is to incorporate compounds in a
      delivery vector that will selectively increase the release of endosomally
      encapsulated DNA. To meet the above criteria, we designed, synthesized, and
      characterized the physicochemical and biological properties of such a compound,
      dodecyl-2-(1'-imidazolyl) propionate (DIP) to enhance cationic liposome mediated
      gene delivery. Several surface active techniques were used to characterize DIP
      lysing membranes. The critical micelle concentration of DIP was between 0.10-0.18
      mM and the effective release and solubilization ratios were 1.0 and 4.0,
      respectively. DIP facilitated membrane disruption in both a pH and concentration
      dependent manner. In the presence of esterase at pH 7.0, the hydrolysis rate
      increased 32-fold indicating DIP can be degraded in the biological milieu.
      Toxicity of DIP by MTT assay in the SKnSH cell line demonstrated an ID50 of 1.2
      mM, which is 30-fold higher than the concentration of DIP used to enhance gene
      transfection. When incorporated into cationic-liposomes, DIP enhanced transgene
      expression in vitro by 5-fold. The results of the study indicate that DIP may be
      a useful adjuvant to increase non-viral gene delivery to cells.

PMID- 9528675
TI  - Lipid composition changes induced by tamoxifen in a bacterial model system.
AB  - A putative relationship between growth impairment of Bacillus stearothermophilus
      by tamoxifen (TAM) and TAM-induced perturbation of the physical properties of
      bacterial membrane lipids has been observed. The supplementation of the growth
      medium with Ca2+ (a membrane stabilizer) partially relieves growth inhibition by
      TAM, allowing growth at TAM concentrations that fully impair growth in the basal
      medium. B. stearothermophilus modifies the membrane lipid composition in response
      to the addition of TAM to the growth medium and the response is sensitive to
      Ca2+. Changes in lipid composition are observed in the acyl chains and in the
      polar head groups of phospholipids. The physical effects of alteration in these
      lipids was studied by fluorescence polarization of DPH and DPH-PA. Polar lipid
      dispersions from TAM-adapted cells grown in a Ca2+ medium show a shift of Tm to
      higher temperatures and a significant increase of the structural order as
      compared to lipids from control cells, suggesting that TAM-induced lipid
      composition changes compensate for the destabilizing effects of the cytostatic on
      membrane organization. The polar lipids from cells grown in the basal medium
      containing tamoxifen are also altered, but these alterations do not promote order
      increase of the bilayer in spite of a deviation of Tm to higher temperatures as
      detected by DPH. Data indicate that B. stearothermophilus controls the membrane
      lipid composition in response to tamoxifen, to compensate for TAM-promoted
      disordering in membranes and to provide an appropriate packing of phospholipid
      molecules in a stable bilayer, putatively disturbed by TAM incorporation.

PMID- 9528676
TI  - Effects of cardiovascular drugs on ATPase activity of P-glycoprotein in plasma
      membranes and in purified reconstituted form.
AB  - Drug interactions with P-glycoprotein (Pgp) were quantitatively assessed using
      ATPase assay. Two experimental systems were used, (i) plasma membranes isolated
      from a multidrug-resistant cell line, which contained 30% Pgp as fraction of
      total membrane protein, and (ii) purified reconstituted Pgp. The cardioactive
      drugs verapamil, quinidine, diltiazem, nifedipine, and a series of digitalis
      analogs, interacted directly with Pgp as shown on ATPase in both systems.
      Apparent affinities of drug binding were calculated. Direct competition was shown
      between digitoxin and verapamil. Drug-drug interaction in vivo at the level of
      Pgp is expected from the results. This approach seems well-suited for empirical
      determination of drug interactions with Pgp, and prediction of drug-drug
      interactions.

PMID- 9528678
TI  - Specific binding to plasma membrane is the first step in the uptake of non
      transferrin iron by cultured cells.
AB  - We studied transport of non-transferrin iron into HeLa cells adapted for growth
      in defined medium, containing either 5 micrograms/ml of iron-saturated
      transferrin (HeLa/Tf cells) or 5 microM ferric citrate (HeLa/Fe5 cells) as a
      source of iron. Employing 55Fe-ferric citrate, iron uptake by intact cells was
      compared with iron binding to isolated membranes. Uptake characteristics of both
      HeLa/Tf and HeLa/Fe5 cells seemed to be similar: Km = 14 microM and Vmax = 135
      pmol Fe/min/10(5) cells for HeLa/Tf, Km = 22 microM and Vmax = 165 pmol
      Fe/min/10(5) cells for HeLa/Fe5. Increasing concentrations (0.3-1.2 microM) of
      55Fe-ferric citrate, producing levels of free 55Fe which were independent of
      total Fe under the experimental conditions used, led to increased binding of 55Fe
      for both HeLa/Tf and HeLa/Fe5 cells (1.08-8.03 nmol Fe/h/10(5) cells). This
      corresponds with the suggestion that iron was bound in the form of ferric citrate
      rather than in the form of free iron. Dissociation constants of Fe binding, KD =
      0.61 microM for HeLa/Tf and KD = 1.53 microM for HeLa/Fe5, were obtained from
      competition experiments. We conclude that specific binding sites for ferric
      citrate are constitutively expressed in plasma membrane and that their expression
      does not require the induction by the presence of ferric citrate. The uptake of
      non-transferrin iron is realized in at least two steps. The first step is iron
      binding to the specific binding sites in plasma membrane. The binding does not
      represent a limiting step of the uptake.

PMID- 9528679
TI  - Structure of yeast plasma membrane H(+)-ATPase: comparison of activated and basal
      level enzyme forms.
AB  - Plasma membrane H(+)-ATPase of the yeast Saccharomyces cerevisiae was isolated
      and purified in its two forms, the activated A-ATPase from glucose-metabolising
      cells, and the basal-level B-ATPase from cells with endogenous metabolism only.
      Structure of the two enzyme forms and the effects of beta, gamma-imidoadenosine
      5'-triphosphate (AMP-PNP) and of diethylstilbestrol (DES) thereon were analysed
      by FT-IR spectroscopy. IR spectra revealed the presence of two populations of
      alpha-helices with different exposure to the solvent in both the A-ATPase and B
      ATPase. AMP-PNP did not affect the secondary structure of A-ATPase while DES
      affected the ratio of the two alpha-helix populations. Thermal denaturation
      experiments suggested a more stable structure in the B-form than in the A-form.
      AMP-PNP stabilised the A-ATPase structure while DES destabilised both enzyme
      forms. IR spectra showed that 60% of the amide hydrogens were exchanged for
      deuterium in both forms at 20 degrees C. The remaining 40% were exchanged at
      higher temperatures. The maximum amount of H/D exchange was observed at 50-55
      degrees C for both enzyme forms, while in the presence of DES it was observed at
      lower temperatures. The data do not contradict the possibility that the
      activation of H(+)-ATPase is due to the C-terminus of the enzyme dissociating
      from the ATP-binding site which is covered by it in the less active form.

PMID- 9528680
TI  - Flavonols--new fluorescent membrane probes for studying the interdigitation of
      lipid bilayers.
AB  - Two flavonols, 3-hydroxy-4'-dimethylaminoflavone (FME) and 3-hydroxy-4'-(15
      azacrown-5) flavone (FRC) have been investigated as new fluorescence probes for
      studying the formation of the interdigitated gel phase in lipid bilayers. The
      formation of the interdigitated gel phase in the saturated symmetrical
      phosphatidylcholines (PCs) and phosphatidylethanol (Peth) in the presence of
      ethanol has been well studied. The present study examines the behavior of these
      new probes in PC-ethanol and Peth-ethanol systems, as well as in PC-cholesterol
      and Peth-cholesterol vesicles. The present results demonstrate that both
      flavonols give distinctively different spectra in interdigitated lipid compared
      to non-interdigitated lipids, when examined in lipids in which the
      interdigitation behavior is known. This makes them useful for determinations of
      the structural state of unknown lipids, and for following the transitions between
      interdigitated and non-interdigitated phases. However, in the presence of
      cholesterol, only FCR gave appropriate indications of interdigitation. The
      results with FME in the presence of cholesterol were not consistent with the
      known behavior of the lipids examined; instead, FME appears to be located
      preferentially in the cholesterol-rich non-interdigitated regions of the bilayer.

PMID- 9528682
TI  - Transport mechanisms for vitamin C in the JAR human placental choriocarcinoma
      cell line.
AB  - We investigated the transport pathways available for the uptake of vitamin C in
      the human placental choriocarcinoma cell line, JAR. These cells were found to
      possess the capacity to accumulate the vitamin when presented either in the
      oxidized form (dehydroascorbic acid) or in the reduced form (ascorbate).
      Dithiothreitol and 5,5'-dithiobis(2-nitrobenzoic acid) were used to maintain
      vitamin C as ascorbate and dehydroascorbic acid, respectively. The uptake of
      these two forms of vitamin C in JAR cells was found to occur by different
      mechanisms. The uptake of the dehydroascorbic acid was Na(+)-independent and was
      mediated by facilitative glucose transporters as evidenced from the inhibition of
      the uptake process by glucose. On the other hand, the uptake of ascorbate was
      Na(+)-dependent and was not sensitive to inhibition by glucose. Substitution of
      Na+ with other monovalent cations abolished the uptake of ascorbate completely.
      The uptake process was, however, not influenced by anions. Kinetic analysis
      indicated the presence of a single saturable transport system for ascorbate with
      a Michaelis-Menten constant of 22 +/- 1 microM. The dependence of the uptake rare
      of ascorbate on Na+ concentration exhibited sigmoidal kinetics, suggesting
      interaction of more than one Na+ ion with the transporter. The Hill coefficient
      for the Na+ interaction was 2, indicating that the Na(+)-dependent ascorbate
      transport is electrogenic. The Na(+)-dependent stimulation of ascorbate uptake
      was primarily due to an increase in the affinity of the transporter for ascorbate
      in the presence of Na+. It is concluded that the JAR placental trophoblast cell
      line expresses two different transport systems for vitamin C: one for the reduced
      form of the vitamin ascorbate; and the other for the oxidized form of the vitamin
      dehydroascorbic acid.

PMID- 9528681
TI  - Helicity, membrane incorporation, orientation and thermal stability of the large
      conductance mechanosensitive ion channel from E. coli.
AB  - In this report, we present structural studies on the large conductance
      mechanosensitive ion channel (MscL) from E. coli in detergent micelles and lipid
      vesicles. Both transmission Fourier transform infrared spectroscopy and circular
      dichroism (CD) spectra indicate that the protein is highly helical in detergents
      as well as liposomes. The secondary structure of the proteins was shown to be
      highly resistant towards denaturation (25-95 degrees C) based on an ellipticity
      thermal profile. Amide H+/D+ exchange was shown to be extensive (ca. 66%),
      implying that two thirds of the protein are water accessible. MscL, reconstituted
      in oriented lipid bilayers, was shown to possess a net bilayer orientation using
      dichroic ratios measured by attenuated total-reflection Fourier transform
      infrared spectroscopy. Here, we present and discuss this initial set of
      structural data on this new family of ion-channel proteins.

PMID- 9528683
TI  - Permeation of redox species through a cell membrane of a single, living algal
      protoplast studied by microamperometry.
AB  - Permeation of several redox species through a cell membrane of a single algal
      protoplast (radius 100 microns) was investigated by amperometry with a Pt
      microdisk electrode (disk radius, 6.5 microns) located near the membrane. The
      redox current observed at the microelectrode decreased as the microelectrode
      approached the cell membrane since the membrane acted as a barrier for diffusion
      of redox species from bulk to the microelectrode. Permeability coefficient (Pm)
      of the protoplast membrane was determined by the quantitative analysis of the
      variation of the redox current with microelectrode-membrane distance using
      digital simulation. The Pm values for Fe(CN)6(4-), Fe(CN)6(3-), Co(phen)3(2+),
      ferrocenyl methanol(FMA) and p-hydroquinone(QH2) were < or = 1.0 x 10(-4), < or =
      1.0 x 10(-4), 1.0 x 10(-3), 5.0 x 10(-3) and 2.0 x 10(-2) cm/s, respectively.
      Using these Pm values, the concentration changes inside a model cell and
      chloroplast were theoretically calculated.

PMID- 9528684
TI  - The influence of the route of administration and liposome composition on the
      potential of liposomes to protect tissue against local toxicity of two antitumor
      drugs.
AB  - The present paper reports on the influence of the route of administration and
      liposome stability on the protective effect of liposome encapsulation of two
      model antitumor agents, mitoxantrone and doxorubicin. The results demonstrate
      that liposome encapsulation can protect surrounding tissue from the cytotoxic
      effects of the drugs after subcutaneous (s.c.) and intramuscular (i.m.)
      administration. The route of administration is an important factor influencing
      tissue damage. Liposomal mitoxantrone caused much less tissue irritation after im
      injection than after s.c. injection. Liposome stability is also an important
      factor. Liposomes composed of 'fluid-state' phospholipids only delayed the
      damaging effects of doxorubicin when injected sc. Liposomes with a more rigid
      nature were much more effective in preventing local tissue damage over a longer
      period of time when administered sc. Results suggest that slow release of
      liposome-associated drugs may eventually cause severe local tissue damage. The
      incorporation of the hydrophilic lipid derivative
      distearoylphosphatidylethanolamine-poly(ethyleneglycol) (PEG-PE) had no apparent
      effect on the protective effect of liposomes after sc administration.

PMID- 9528685
TI  - Characterization of L-arginine uptake by plasma membrane vesicles isolated from
      cultured pulmonary artery endothelial cells.
AB  - We investigated the mechanisms of [3H]-L-arginine transport via System Y+ using
      plasma membrane vesicles derived from cultured pulmonary artery endothelial
      cells. [3H]-L-arginine uptake into plasma membrane vesicles was Na-independent,
      sensitive to trans-stimulation, unaffected by proton-conducting ionophores, and
      selectively inhibited by cationic amino acids. Kinetic experiments performed over
      a wide range of substrate concentrations revealed only one population of L
      arginine transporters with Km = 130 microM. To elucidate the driving force for L
      arginine transport, we measured [3H]-L-arginine uptake by plasma membrane
      vesicles at different transmembrane ion gradients. Plasma membrane vesicles
      accumulated [3H]-L-arginine only when a membrane potential was imposed across the
      vesicles, and the velocity of uptake was linearly related to the magnitude of the
      created membrane potential. The presence of potassium ions inside the vesicles
      was not essential for uptake of L-arginine into vesicles, but it was essential
      for trans-stimulation of L-arginine transport. [3H]-L-arginine accumulated in
      plasma membrane vesicles can be released by agents that dissipate transmembrane
      potassium gradients (e.g. saponin, gramicidin, and nigericin). Diazoxide and
      pinacidil, activators of K(+)-channels, had no significant effect on [3H]-L
      arginine uptake, whereas tetraethylammonium chloride, 4-aminopyridine, and
      glibenclamide, inhibitors of K(+)-channels, caused decreases in [3H]-L-arginine
      transport by plasma membrane vesicles. This study demonstrates for the first time
      a specific role for potassium ions in the mechanism of L-arginine transport,
      particularly in the phenomenon of trans-stimulation.

PMID- 9528686
TI  - Reactions of halogen-substituted aziridinylbenzoquinones with glutathione.
      Formation of diglutathionyl conjugates and semiquinones.
AB  - The reaction between glutathione and 2,5-diaziridinyl-1,4-benzoquinones bearing
      halogen substituents at C3 and C6 was examined in terms of the formation of
      glutathionyl-quinone conjugates and semiquinones by HPLC with UV detection, mass
      spectroscopy and EPR. The reactivity of the halogen atoms toward sulfur
      substitution is the primary reaction leading to the formation of mono- and di
      glutathionyl-substituted quinones. The relative formation of these conjugates
      depended on the GSH/quinone molar ratios. At GSH/quinone molar ratios below
      unity, the products observed were the reduced form of the parent quinone, a
      dithioether derivative and GSSG. Disulfide formation accounted for 60-68% of
      total GSH consumed. EPR analysis of these reaction mixtures showed a 5-line
      spectrum (1:2:3:2:1 relative intensities) with 2 equivalent N (aN = 1.98 G) and
      assigned to the semiquinone form of dichloro- diaziridinylbenzoquinone.
      Semiquinone quantification by double integration of the EPR signals and
      interpolation with an adequate standard revealed that the amount of semiquinone
      formed per GSH consumed was 0.98. At GSH/quinone molar ratios above unity (4, 10
      and 100 molar excess of GSH) a pattern of products emerged consisting of 3,6
      diglutathionyl quinones with two, one and no aziridinyl moieties, identified by
      mass spectral analysis. EPR studies revealed that these compounds were minor
      components of a composite EPR spectrum (a 3-line signal with 1:1:1 relative
      intensities, 1 equivalent N (aN = 1.73 G) and 1 H (aH = 1.45 G) or a 3-line
      signal with 1:2:1 relative intensities and 2 equivalent H (aH = 1.4 G). These
      minor components were assigned to the diglutathionyl conjugates bearing one- or
      no aziridinyl moiety, respectively. The major component in the EPR signal showed
      a 3-line spectrum (1:1:1 relative intensity) with 1 equivalent N (aN = 1.7 G) and
      a g shift of -0.96 G. This spectrum was assigned to a triglutathionyl conjugate
      of a monoaziridinylbenzoquinone. This major component was also observed when
      GSH/quinone mixtures were incubated with the two-electron transfer flavoprotein
      NAD(P)H:quinone oxidoreductase. The semiquinone signals were abolished by
      superoxide dismutase. In the presence of catalase, the contribution of these
      components to the overall EPR spectrum was equal. These data are discussed in
      terms of the one-electron transfer steps encompassed by thiol oxidation and
      semiquinone formation and the two-electron transfers inherent in sulfur
      substitution and aziridinyl group loss.

PMID- 9528687
TI  - Effects of butylated hydroxyanisole and dicoumarol on the toxicity of menadione
      to rats.
AB  - The enzyme DT-diaphorase catalyses the 2-electron reduction of quinones. This
      reaction may facilitate the detoxification of such compounds, since the
      hydroquinone so formed can be converted into non-toxic conjugates. There is
      evidence for the involvement of DT-diaphorase in the detoxification of menadione
      (2-methyl-1,4-naphthoquinone) in a wide range of cells and tissues in vitro, but
      no information is available on the possible influence of this enzyme on the
      harmful effects of menadione in vivo. In animals, menadione is selectively toxic
      to erythrocytes, causing haemolytic anaemia. In the present study, rats were
      treated with dicoumarol, an inhibitor of DT-diaphorase, or butylated
      hydroxyanisole (BHA), a substance that increases the activity of this enzyme in
      vivo. They were then challenged with a toxic dose of menadione. Dicoumarol
      increased the severity of menadione-induced haemolytic anaemia while BHA
      decreased it, consistent with a role for DT-diaphorase in the detoxification of
      menadione in vivo, as previously described in vitro.

PMID- 9528688
TI  - Isolation and analysis of dityrosine from enzyme-catalyzed oxidation of tyrosine
      and X-irradiated peptide and proteins.
AB  - Dityrosine (DT) was isolated in a single-step by reversed-phase HPLC in 25% yield
      from enzyme-catalyzed oxidation of N-acetyl tyrosine followed by deacetylation.
      The isolated product was characterized by 1H NMR. A three-step chromatographic
      procedure was reported to facilitate the preparation of DT from the enzyme
      catalyzed oxidation of tyrosine in 26% yield of theoretical maximum. Upon
      irradiation at 284 nm in acidic and 315 nm alkaline conditions, DT exhibits
      strong fluorescence at 400 nm-range. However, when excited at 300 nm-range,
      contribution of similar fluorescence by Trp oxidation and other protein
      modifications cannot be overruled. In order to identify the formation of DT
      unequivocally, Tyr was subjected to X-irradiation under nitrogen at pH 4 and
      labeled with dansyl chloride. HPLC conditions were devised to resolve dansylated
      DT from dansylated standard amino acids. Radiation-induced DT was identified by
      cochromatography with a dansylated, authentic sample of DT isolated and
      characterized from enzyme-catalyzed oxidation of Tyr. The formation of DT in the
      irradiated samples, determined by the integrated peak area, increased with dose
      (0-600 Gy). HPLC analysis of dansylated hydrolysate of the major product from an
      irradiated tripeptide (Tyr Gly Gly) detected Gly and DT (2:0.5). Extension of the
      model study to irradiated BSA and RNase A also showed DT as the major oxidation
      product of Tyr under the experimental conditions. Fluorescence signal of
      dansylated DT was linear from 0.5 pmol to 1.5 nmol (correlation coefficient
      0.999, n = 3). The detection limit 0.5 pmol per 5 microliters injection
      hydrolysate corresponds to one molecule of DT per 300 molecules of BSA (BSA at 1
      mg/ml). DT can be used as a marker for assessing oxidative damage of proteins.
      Most standard amino acid analysis techniques are limited to detect normal
      residues of proteins. The assay reported in the present study has potential for
      low-level detection of DT unequivocally and may be useful for monitoring
      oxidative stress-related physiological and pathological processes.

PMID- 9528689
TI  - A stereospecific phosphotriesterase in hen liver and brain.
AB  - O-Hexyl, O-2,5-dichlorophenyl phosphoramidate (HDCP) is a chiral compound that
      induces delayed neuropathy in hens. This compound is hydrolyzed by a
      phosphotriesterase known as HDCPase in hen and rat plasma, liver and brain. We
      studied the stereospecificity of HDCPase in hen tissues and in human and rabbit
      plasma employing a chromatographic method for analysis and quantification of HDCP
      stereoisomers. Hen and human plasma HDCPases were not stereospecific. However,
      rabbit plasma showed a remarkable stereospecificity to S-(-)-HDCP. High levels of
      stereospecific HDCPase were found in the particulate fraction of hen liver, where
      S-(-)-HDCP is hydrolyzed faster than R-(+)-HDCP. However, in hen brain the
      stereospecificity was found in the soluble fraction, where R-(+)-HDCP is
      hydrolyzed faster than S-(-)-HDCP. It is concluded that liver particulate
      fraction must be the main tissue responsible for the HDCP stereospecific
      biotransformation in hens. In an oral administration, the steroisomer R-(+)-HDCP
      would survive after passing through the liver and would interact with
      acetylcholinesterase and neuropathy target esterase in the nervous system.

PMID- 9528690
TI  - Formation of DNA adducts in human buccal epithelial cells exposed to acetaldehyde
      and methylglyoxal in vitro.
AB  - Acetaldehyde (AA) and methylglyoxal (MG) are reactive, ubiquitous aldehydes,
      present in the environment and endogenously formed in animals and humans. They
      have both been shown to readily form DNA adducts under simulated physiological
      conditions. We report here on the use of cultured normal and SV40T antigen
      immortalized human buccal epithelial cells as model systems for aldehyde exposure
      of the oral epithelium, occurring through the ingestion of alcoholic beverages
      and brewed coffee, as well as by inhalation of tobacco smoke and automobile
      exhaust. By the application of recently developed 32P-postlabeling methods, the
      presence of both endogenous and induced AA and MG DNA adducts was demonstrated in
      cultured human epithelial cells. Furthermore, these DNA adducts were formed in a
      dose-dependent manner at aldehyde concentrations that were relatively nontoxic to
      the cells.

PMID- 9528691
TI  - The formation and repair of cisplatin-DNA adducts in wild-type and cisplatin
      resistant L1210 cells: comparison of immunocytochemical determination with
      detection in isolated DNA.
AB  - We have studied the formation and repair of cisplatin-DNA adducts in wild-type
      mouse leukemia L1210/0 cells and in the sublines L1210/2 and L1210/5, which
      differ in cisplatin sensitivity. In a colony-formation assay these sublines were
      9- and 22-fold more resistant compared to L1210/0, respectively. Cisplatin
      induced DNA modification was studied at the cellular level by immunocytochemistry
      with antiserum NKI-A59 raised against cisplatin-treated DNA. Levels of nuclear
      staining immediately after a 1-h treatment were similar to those seen after a 24
      h post-incubation in drug-free medium. Clear differences in DNA platination were
      found between the cell lines: immediately after exposure, L1210/2 and L1210/5
      showed only 32 and 14%, respectively, of the nuclear staining observed in
      L1210/0, and 48 and 13% after 24 h. In these experiments, adduct-specific nuclear
      staining was quantified as the area under the adduct versus concentration curves
      (AUC). The formation and repair in these cell lines of the bifunctional adducts
      cis-Pt(NH3)2d(pGpG) (Pt-GG), cis-Pt(NH3)2d(pApG) (Pt-AG) and cis-Pt(NH3)2(dGMP)2
      (G-Pt-G) were studied with an enzyme-linked immunosorbent assay (ELISA). No
      relation between repair and resistance was observed. The results suggest that
      differences in induced DNA platination levels, rather than in repair, are
      responsible--at least in part--for the differences in cisplatin resistance. A
      mechanism such as an increased tolerance of the resistant cells to plantinum-DNA
      damage may also be involved.

PMID- 9528692
TI  - Contamination by PCB's, DDT's, and heavy metals in sediments of Ho Chi Minh
      city's canals, Viet Nam.

PMID- 9528693
TI  - Identification and determination of low-molecular weight organic compounds in
      contaminated fog water using proton nuclear magnetic resonance spectroscopy.

PMID- 9528694
TI  - Distribution of imidacloprid in soil following subsurface drip chemigation.

PMID- 9528695
TI  - Methodology and determination of 2,4-D and triclopyr residues employing the GC
      ITD in the analysis of lettuce plants cultivated in the Tala Valley, Republic of
      South Africa.

PMID- 9528696
TI  - Empirical investigation of hand-to-mouth transfer of soil.

PMID- 9528697
TI  - DNA adduct formation by the pesticide alachlor and its metabolite 2-chloro-N-(2,6
      diethylphenyl)acetamide (CDEPA).

PMID- 9528698
TI  - Urinary excretion of total and inorganic lead in tetraethyllead exposed workers.

PMID- 9528699
TI  - Zinc levels in rice and in soil according to the soil types of Japan, Indonesia,
      and China.
AB  - The means of zinc levels in rice of Japan, Indonesia and China were practically
      identical, 23.38, 23.51, and 21.47 micrograms/g for Japan, Indonesia and China
      respectively. Regarding soil, Japan seemed to have an higher concentration of
      zinc. When samples were divided by soil type, Histosols (all samples from
      Indonesia) appeared to contain the highest (27.37 micrograms/g) and Acrisols the
      lowest (21.04 micrograms/g) zinc level among all the soil types. Mixed soils, 10
      out of 18 samples from China, had the highest concentration of zinc both using
      hydrochloric extracting method and the nitric acid ashing method. The
      relationship of zinc in rice to the types of soils was insignificant. It appears
      that zinc contents in rice and soil are not influenced by soil type. Total
      dietary intakes of zinc of the people from Japan, Indonesia and China were 24.3,
      21.9 and 22.7 mg/person, respectively, which was higher than the recommended
      dietary allowance of daily zinc intake from foods by the American standard diet
      (15 mg/person).

PMID- 9528700
TI  - Accumulation of selenium by the aquatic biota of a watershed treated with
      seleniferous fertilizer.

PMID- 9528701
TI  - Metals pollution in marine sediments of the United Arab Emirates creeks along the
      Arabian Gulf shoreline.

PMID- 9528702
TI  - Comparison of digestion techniques in analyses for total metals in marine
      sediments.

PMID- 9528703
TI  - Accumulation of resin acids in sediments adjacent to a log handling area,
      Tauranga harbour, New Zealand.

PMID- 9528704
TI  - Effects of organophosphorus, carbamate, pyrethroid and organochlorine pesticides,
      and a heavy metal on survival and cholinesterase activity of Chironomus riparius
      Meigen.

PMID- 9528705
TI  - Toxicity testing of refinery wastewater using Microtox.

PMID- 9528706
TI  - Biochemical oxygen demand exertion and glucose uptake kinetics of Azotobacter in
      crude oil polluted medium.

PMID- 9528707
TI  - Effects of trifluoroacetate, an atmospheric breakdown product of
      hydrofluorocarbon refrigerants, on acetate metabolism by freshwater benthic
      microbial communities.

PMID- 9528708
TI  - Midgut pathology of aldrin, monocrotophos, and carbaryl in the freshwater crab,
      Paratelphusa masoniana, (Henderson).

PMID- 9528709
TI  - Effect of EDTA on reduction of copper toxicity in Oreochromis mossambicus
      (Peters).

PMID- 9528710
TI  - Histopathological changes within the testis caused by allyl chloride exposure in
      mice.

PMID- 9528711
TI  - Evaluation of trihalomethanes in water treatment plants' outputs in Cairo, Egypt
      during 1991 to 1993.

PMID- 9528712
TI  - Fitting in integrated delivery systems: advice for department chairs.

PMID- 9528713
TI  - Association between anterior ST depression and increased myocardial salvage
      following reperfusion therapy in patients with inferior myocardial infarction.
AB  - PURPOSE: To determine electrocardiographic features associated with myocardial
      salvage following reperfusion therapy in patients with inferior myocardial
      infarction. PATIENTS AND METHODS: Ninety-two consecutive patients with acute
      inferior myocardial infarction were treated with reperfusion therapy in a
      tertiary care center. Several features were measured on the presenting
      electrocardiogram, including the presence or absence of ST depression in the
      chest leads and the total magnitudes of ST elevation or depression, and were then
      evaluated for their association with myocardial salvage. Myocardial salvage (% of
      left ventricle) was the difference between myocardium at risk and final infarct
      size. Tomographic myocardial perfusion imaging with technetium-99m sestamibi was
      performed acutely to measure myocardium at risk and repeated prior to hospital
      discharge to measure final infarct size. RESULTS: The amount of myocardium at
      risk of infarction in the 92 patients was 19.1%+/-11.3% (range 1% to 68%), and
      the final infarct size was 10.6%+/-10.0% (range 0% to 45%). Thus, myocardial
      salvage in the 92 patients was 8.5%+/-8.4% (range -11% to 35%) of the left
      ventricle, or 0.51+/-0.38 (range 0.0 to 1.0) when expressed as a fraction of the
      myocardium at risk (salvage index). The presence or absence of anterior ST
      depression was the only one of seven electrocardiographic variables that was
      associated with myocardial salvage. Myocardial salvage was significantly greater
      in patients with anterior ST depression compared with those without it (10.6%+/
      9.0% versus 5.9%+/-6.7%, P=0.025). Myocardium at risk was significantly greater
      in patients with anterior ST depression compared with those without the
      depression (22.8%+/-12.2% versus 14.6%+/-8.3%, P=0.0006), and infarct size tended
      to be larger (12.1%+/-10.4% versus 8.7%+/-9.4%, P=0.10). Myocardial salvage as a
      fraction of the myocardium at risk (salvage index) was similar between the two
      patient groups (0.52+/-0.37 versus 0.50+/-0.39, P=NS). CONCLUSION: The presence
      of anterior ST depression during inferior myocardial infarction identifies a
      group of patients with the potential for greater myocardial salvage with
      reperfusion therapy. Such patients derive greater absolute benefit from
      reperfusion therapy because they have a larger amount of myocardium at risk,
      although their response to therapy (salvage index) is not intrinsically
      different.

PMID- 9528714
TI  - Diagnosis and outcome of 100 consecutive patients with extreme granulocytic
      leukocytosis.
AB  - PURPOSE: To determine the clinical features, causes, and prognostic significance
      of extreme leukocytosis in adults. PATIENTS AND METHODS: Medical records of 100
      consecutive patients who presented at the Minneapolis Veterans Affairs Medical
      Center between March 1993 and January 1994 with more than 25,000
      leukocytes/microL blood and with more than 50% granulocytes were reviewed.
      Demographic, clinical, and outcome information was recorded, and a cause of
      extreme leukocytosis was sought in each case. RESULTS: Extreme leukocytosis was
      attributed to infection in 48 cases, advanced malignancy in 13 cases, hemorrhage
      in 9 cases, glucocorticoids in 8 cases, and other causes in 22 cases. Four
      patients had previously diagnosed conditions resulting in chronic leukocytosis.
      Higher leukocyte counts were associated with malignancy (chi2 for trend=12.5, P
      <0.002). Fever was more common in patients with infection (weighted rate
      ratio=3.7, 95% Confidence interval [CI]=2.2 to 6.2). Mortality was high overall
      (31%), and was greater in patients with noninfectious diagnoses compared with
      infected patients, an association which persisted after stratification by
      leukocyte count (weighted rate ratio=2.5, 95% CI=1.2 to 4.9). CONCLUSION:
      Clinicians should be aware that extreme leukocytosis with a predominance of
      granulocytes is associated with infection in only 48% of cases. The presence of
      fever increases the likelihood that infection is the cause. Mortality is high,
      particularly in patients without infection.

PMID- 9528715
TI  - Variations in antimicrobial use and cost in more than 2,000 patients with
      community-acquired pneumonia.
AB  - PURPOSE: To assess the patterns of antimicrobial use, costs of antimicrobial
      therapy, and medical outcomes by institution in patients with community-acquired
      pneumonia. PATIENTS AND METHODS: The route, dose, and frequency of administration
      of all antimicrobial agents prescribed within 30 days of presentation were
      recorded for 927 outpatients and 1328 inpatients enrolled in the Pneumonia
      Patient Outcomes Research Team (PORT) multicenter, prospective cohort study.
      Total antimicrobial costs were estimated by summing drug costs, using average
      wholesale price for oral agents and institutional acquisition prices for
      parenteral agents, plus the costs associated with preparation and administration
      of parenteral therapy. Thirty-day outcome measures were mortality, subsequent
      hospitalization for outpatients, and hospital readmission for inpatients.
      RESULTS: Significant variation (P <0.05) in prescribing practices occurred for 17
      of the 23 antimicrobial agents used in outpatients across 5 treatment sites, and
      for 18 of the 20 parenteral agents used in inpatients across 4 treatment sites.
      The median duration of antimicrobial therapy for treatment site ranged from 11 to
      13 days for outpatients (P=0.01), and from 13 to 15 days for inpatients (P=0.49).
      The overall median cost of antimicrobial therapy was $12.90 for outpatients, and
      ranged from $10.80 to $58.90 among treatment sites (P <0.0001). The overall
      median cost of antimicrobial therapy was $228.70 for inpatients, and ranged from
      $183.70 to $315.60 among sites (P <0.0001). Mortality and hospital readmission
      for inpatients were not significantly different across sites after adjusting for
      baseline differences in patient demographic characteristics, comorbidity, and
      illness severity. Although subsequent hospitalization for outpatients differed by
      site, the rate was lowest for the site with the lowest antimicrobial costs.
      CONCLUSION: Variations in antimicrobial prescribing practices by treatment site
      exist for outpatients and inpatients with community-acquired pneumonia. Although
      variation in antimicrobial prescribing practices across institutions results in
      significant differences in antimicrobial costs, patients treated at institutions
      with the lowest antimicrobial costs do not demonstrate worse medical outcomes.

PMID- 9528716
TI  - Randomized trial of trovafloxacin and ofloxacin for single-dose therapy of
      gonorrhea. Trovafloxacin Gonorrhea Study Group.
AB  - PURPOSE: To compare trovafloxacin, a new quinolone antibiotic with enhanced
      activity against Neisseria gonorrhoeae, with ofloxacin as single-dose oral
      therapy for uncomplicated gonococcal urethritis or cervicitis. PATIENTS AND
      METHODS: In this multicenter, double-blind trial, 625 patients (270 men, 355
      women) with uncomplicated gonococcal urethritis or cervicitis received one 100-mg
      tablet of trovafloxacin or two 200-mg capsules of ofloxacin as a single dose
      under direct supervision. RESULTS: Single-dose oral therapy with trovafloxacin
      was equivalent both bacteriologically and clinically to ofloxacin. Among
      evaluable patients, N gonorrhoeae was eradicated in 99% of trovafloxacin
      recipients and in 98% of ofloxacin recipients. Each treatment was well tolerated;
      vaginitis was the most frequently observed side effect (4% trovafloxacin, 7%
      ofloxacin). CONCLUSION: Based on the results presented here, trovafloxacin is a
      promising agent for single-dose therapy of uncomplicated gonorrhea.

PMID- 9528717
TI  - Randomized trial of itraconazole oral solution for oropharyngeal candidiasis in
      HIV/AIDS patients.
AB  - PURPOSE: Oropharyngeal candidasis (thrush) is the most common opportunistic
      infection in individuals who are positive for the human immunodeficiency virus
      (HIV) and those who have progressed to AIDS. Itraconazole has a broad in vitro
      spectrum of activity, including a wide variety of Candida species. Our study
      determined the relative efficacy of a new oral solution formulation of
      itraconazole and fluconazole tablets in the treatment of oropharyngeal
      candidiasis. PATIENTS AND METHODS: This was a prospective randomized, third-party
      blind, multicenter trial conducted at 12 centers in the United States. One
      hundred seventy-nine HIV-positive patients with mycologically documented
      oropharyngeal candidiasis were treated with itraconazole oral solution 200 mg/
      day for 7 or 14 days, or fluconazole tablets 100 mg/day for 14 days. Severity of
      disease was scored clinically before treatment and at clinical evaluations on
      days 3, 7, 14, 21, 35, and 42. Semi-quantitative cultures of mouth washings were
      also obtained on these days. RESULTS: Both 14-day and 7-day regimens of
      itraconazole oral solution were equivalent to fluconazole for most efficacy
      parameters. The clinical response rate was 97% after 14 days of itraconazole and
      87% after 14 days of fluconazole. Itraconazole oral solution given for 7 days was
      also equivalent to fluconazole treatment for 14 days. Approximately one half of
      patients in all three groups relapsed by 1 month after completion of treatment.
      There were few adverse reactions to either drug. CONCLUSION: Itraconazole oral
      solution is well tolerated and offers an alternative at least as effective as
      fluconazole in the treatment of oropharyngeal candidiasis.

PMID- 9528718
TI  - Prevalence of hypophosphatemia in sepsis and infection: the role of cytokines.
AB  - BACKGROUND: Sepsis occurs following the presence of bacteria in the circulation
      and is associated with fever, hyperthermia, and hypotension. Hypophosphatemia
      develops in the early stages of sepsis. High levels of inflammatory cytokines
      also characterize early sepsis. AIM: The aim of the present study was to
      correlate hypophosphatemia with cytokines and cytokine receptor levels during
      early sepsis. We aimed to reestablish the results obtained from patients in an in
      vivo experimental model, in order to understand the mechanism of hypophosphatemia
      induction in early sepsis. METHODS: Ninety-nine patients were enrolled in this
      study and their clinical condition was classified as the presence of infection,
      sepsis, and bacterial growth in blood cultures. Phosphate levels and cytokine
      levels were recorded. In order to determine whether hypophosphatemia is
      correlated to the increased inflammatory cytokines, we injected normal mice with
      recombinant cytokines and studied their effect on phosphate levels. RESULTS: Our
      results revealed that 80% of the septic patients had hypophosphatemia associated
      with very high levels of tumor necrosis factor (TNF)alpha and interleukin (IL)-6
      and of soluble IL receptor (sIL)-2R and IL-6R, especially in those patients with
      positive blood cultures. Injection of IL-6, TNFalpha and IL-1beta in mice
      markedly decreased the phosphate serum levels. CONCLUSIONS: Significant
      associations were demonstrated between high levels of inflammatory cytokines and
      their receptors and between serum phosphate levels, especially in patients with
      positive blood culture. Our results point to a correlation between the high
      inflammatory cytokines levels and hypophosphatemia during early sepsis. Cytokine
      levels and hypophosphatemia may be included in sepsis evaluation and prognosis.
      Anticytokine strategies might, therefore, reverse hypophosphatemia and other
      parameters of sepsis.

PMID- 9528719
TI  - Granulocyte colony-stimulating factor use is associated with decreased bacteremia
      and increased survival in neutropenic HIV-infected patients.
AB  - BACKGROUND: Neutropenia occurs in up to 17% of human immunodeficiency virus (HIV)
      infected individuals. Although granulocyte colony-stimulating factor (G-CSF) can
      reverse HIV-related neutropenia, it is not established that this therapy can
      reduce bacterial infections and affect survival. METHODS: A retrospective cohort
      study of 152 neutropenic, HIV-infected patients was performed to determine the
      therapeutic utility of G-CSF. Medical records of 71 patients who received G-CSF
      and 81 patients who never received G-CSF, during the years of 1991 to 1994 at
      Parkland Memorial Hospital, were reviewed for the incidence of bacteremia, G-CSF
      use, antiretroviral therapy (AR), Pneumocystis carinii pneumonia prophylaxis
      (PCPP), and opportunistic infections (OI). RESULTS: The two patient groups had
      similar baseline characteristics including CD4 count (37 cells/mm3 versus 40
      cells/ mm3, P=0.7). Univariate analysis revealed and trend toward decreased rates
      of all bacteremias in the G-CSF-treated group compared with the controls (0.54
      bacteremias/100 patient months versus 2.2 bacteremias/100 patient months,
      P=0.064) and a marked decrease in the rates of gram-negative rod bacteremias in
      the G-CSF-treated group compared with the untreated group (0.09 gram-negative rod
      bacteremias/100 patient months versus 1.7 gram-negative rod bacteremias/100
      patient months, P=0.002). In a multivariate analysis, significant decreased risk
      for bacteremia was found with G-CSF use (odds ratio [OR]=0.15, P=0.02). Survival
      was longer in patients treated with G-CSF than in the untreated group (median:
      397 days versus 165 days). Multivariate analysis using Cox Proportional Hazards
      Model showed decreased risk of death in patients treated with G-CSF, ARs, PCPP.
      CONCLUSIONS: We conclude that G-CSF use is associated with decreased bacteremias
      and is associated with prolonged survival in neutropenic, HIV-infected patients.

PMID- 9528720
TI  - Prevalence and causes of undernutrition in medical outpatients.
AB  - PURPOSE: To assess the prevalence, common causes, and frequency of recognition
      and treatment of undernutrition in older and younger medical outpatients using a
      cross-sectional survey design with 2-year follow-up of undernourished subjects.
      PATIENTS AND METHODS: Charts of 1017 adult patients attending a hospital
      outpatient department were reviewed for the presence of undernutrition, and 85
      patients meeting inclusion criteria for undernutrition were evaluated and
      followed for 2 years. An initial evaluation focused on nutritional, cognitive,
      and affective status and on nutritional attitudes using two subscales of the EAT
      26 eating disorder inventory. After 2 years, initial data plus outpatient records
      were evaluated by 2 independent reviewers to determine a primary cause of
      undernutrition and to assess the recognition and treatment of undernutrition by
      the primary physician. RESULTS: Undernutrition was identified in 46 (11%) and 44
      (7%) of older and younger subjects respectively; odds ratio (OR) (95% [confidence
      interval (CI)]) for older versus younger=1.65 (1.06 to 2.51). The primary cause
      of undernutrition differed between age groups but was deemed treatable in nearly
      90% of all subjects. Undernutrition was recognized in 19 (43%) older subjects and
      5 (12%) younger subjects (OR=5.47 [1.87 to 16.0]), and appropriate
      intervention(s) were instituted in 6 (14%) and 2 (5%) of older and younger
      subjects, respectively (OR=3.08 [0.668 to 14.21]). Older subjects scored higher
      on the EAT-26 oral control subscale than did younger subjects (4.7 versus 2.5,
      P=0.004) but similarly on the EAT-26 dieting subscale (5.2 versus 6.3, P=0.332);
      these relationships did not change with control for potentially confounding
      variables. CONCLUSIONS: In this study, undernutrition was relatively common,
      usually amenable to treatment, but frequently undetected and undertreated in both
      older and younger medical outpatients. Older undernourished subjects exhibited
      higher oral control needs than younger persons, which may have implications for
      the pathophysiology and treatment of their malnutrition. Further improvement in
      detection and intervention is warranted in both younger and older age groups.

PMID- 9528721
TI  - Does bedside rationing violate patients' best interests? An exploration of "moral
      hazard".

PMID- 9528722
TI  - Evaluation of hibernating myocardium in patients with ischemic heart disease.
AB  - Patients with ischemic heart disease and significant left ventricular dysfunction
      are often difficult to manage medically. Revascularization procedures may improve
      left ventricular function and prognosis in this population if hypocontractile yet
      viable myocardium (hibernating myocardium) is demonstrated. Nuclear cardiology
      studies (single photon and positron methods), two-dimensional echocardiography,
      and magnetic resonance imaging studies have been utilized to identify hibernating
      myocardium. If thallium-201 studies are performed, the use of reinjection of
      thallium and repeat imaging improves the sensitivity of these studies for the
      detection of viable myocardium. Dobutamine echocardiographic studies may have a
      higher specificity and positive predictive value for the subsequent improvement
      of regional systolic left ventricular function after revascularization than the
      nuclear techniques. However, thallium studies have an excellent negative
      predictive value. Positron emission tomography (PET) allows the simultaneous
      assessment of perfusion and metabolic activity; however, these studies are
      expensive and not widely available. Functional evaluation with PET is in its
      infancy. Functional cardiac magnetic resonance imaging (MRI), although not widely
      available yet, provides the most accurate evaluation of regional ventricular
      function. MRI spectroscopy may be utilized to assess myocardial viability. As
      acquisition times improve and "real-time" imaging becomes a reality, MRI and MRI
      spectroscopy will likely become very accurate tools for assessing functional
      reserve and metabolic activity. The selection of the most appropriate method for
      assessment of myocardial viability will include consideration of a patient's
      characteristics, the presence of coronary arterial tree amenable to
      revascularization techniques, the techniques available to the clinician to assess
      viability, and local revascularization experience in this population. The result
      of an individual patient's evaluation is relevant to the consideration of
      coronary revascularization, or if this is not possible, cardiac transplantation.

PMID- 9528723
TI  - Percutaneous stenting of superior vena cava syndrome: a case report and review of
      the literature.
AB  - Superior vena cava syndrome (SVCS) is a distressing manifestation of benign or
      malignant disease obstructing return of blood flow through the superior vena cava
      (SVC). Treatment, often centering around management of the underlying illness,
      may be slow in relieving symptoms, relying on the recruitment of collateral veins
      to reestablish blood flow. Percutaneous delivery of metallic stents into the vena
      cava has been used with success to relieve obstruction to blood flow quickly and
      completely. We present the case of a patient with complete occlusion of the SVC
      who underwent successful vena caval revascularization with placement of balloon
      expandable metallic stents. We also review published reports on the use of stents
      for SVCS. Results from several series demonstrate that stents can be used with
      excellent results. Response rates in these series reviewed range from 68% to
      100%. Recurrence of symptoms occurred in 4% to 45% of patients but could often be
      treated with anticoagulation, angioplasty of the stented area, or repeat
      stenting. Stenting has been used successfully in patients with malignant diseases
      and in the less common cases of SVCS from a benign etiology. Complications are
      uncommon and usually of minor consequence. Anticoagulation, thrombolytics, and
      thrombectomy or atherectomy catheters have also been used during or following
      stent implantation although their use remains primarily empiric. Percutaneous
      treatment of SVC obstruction offers patients hope for prompt and dramatic relief
      from the symptoms of SVCS.

PMID- 9528724
TI  - General principles of the structure of ion channels.

PMID- 9528725
TI  - A new human retrovirus: a role in lymphoma?

PMID- 9528726
TI  - False-positive antineutrophil cytoplasmic antibodies in a patient with cavitary
      pulmonary sporotrichosis.

PMID- 9528727
TI  - Caring for adults: a comparison of three residency options.

PMID- 9528728
TI  - Survival after the diagnosis of hyperparathyroidism: a population-based study.
AB  - BACKGROUND: Reports of increased mortality from cardiovascular disease and
      malignancy in primary hyperparathyroidism have been based primarily on patients
      who have undergone parathyroidectomy. In order to assess the true impact of
      primary hyperthyroidism on mortality in the general population, we assessed
      survival in a large inception cohort of Rochester, Minnesota residents with
      primary hyperparathyroidism initially diagnosed over a 28-year span, the majority
      of whom were followed with uncomplicated disease. METHODS: All Rochester
      residents with primary hyperparathyroidism first recognized in 1965 to 1992 were
      identified through the Rochester Epidemiology Project medical records linkage
      system. Included as cases were patients with pathologic confirmation of
      hyperthyroidism, hypercalcemia with inappropriately elevated parathyroid hormone
      levels, or hypercalcemia for more than a year with no other cause. Survival was
      estimated using the Kaplan Meier product-limit method. The Cox proportional
      hazards model was used to determine associations, as relative hazards (RR) with
      95% confidence intervals (CI), of various risk factors with time to death.
      RESULTS: During the study period, 435 cases of primary hyperparathyroidism were
      identified. Altogether, parathyroid surgery was performed on 126 patients (29%),
      with a mean delay between the initial elevated serum calcium level and surgery of
      3.3 years. Patients who underwent surgery had higher maximum serum calcium levels
      than the patients who were observed (mean+/-SD, 11.3+/-0.7 versus 10.7+/-0.4
      mg/dL, P <0.00 1), but their mean ages were similar (54+/-16 versus 56+/-17
      years). Overall survival in the patients with primary hyperthyroidism was better
      than expected (P=0.02), but by age-adjusted multivariate analysis, higher maximal
      serum calcium level was an independent predictor of mortality (RR=1.3 per mg/dL;
      95% CI: 1.1-1.6; P <0.02). CONCLUSION: Overall survival is not adversely affected
      among unselected patients with mild primary HPT in the community, although
      patients with more severe disease, as manifested by higher serum calcium levels,
      may have an increased risk of death.

PMID- 9528729
TI  - The yield of bone marrow biopsy and culture compared with blood culture in the
      evaluation of HIV-infected patients for mycobacterial and fungal infections.
AB  - PURPOSE: To compare the clinical utility of bone marrow biopsy and culture
      specimens with blood cultures for mycobacterial and fungal infections among human
      immunodeficiency virus (HIV)-infected patients. PATIENTS AND METHODS: All bone
      marrow biopsies obtained from HIV-infected patients at the University of Alabama
      at Birmingham (UAB) Medical Center during 1993 to 1995 were blindly reviewed in a
      standardized format. Bone marrow culture results and blood culture results
      obtained within 6 weeks of each bone marrow study were compiled. Medical records
      were reviewed to determine indications for performing bone marrow biopsies,
      empiric or prophylactic antimicrobial therapies preceding the biopsy, and CD4
      counts. RESULTS: Eighty-two bone marrow studies were obtained from 76 patients.
      Most were performed during the evaluation of fever, cytopenia, or weight loss. Of
      55 bone marrow mycobacterial cultures, 13 yielded Mycobacterium avium complex
      (MAC) and 2 yielded M tuberculosis (MTB). Of 51 bone marrow fungal cultures
      performed, 2 yielded Cryptococcus neoformans and 1 Histoplasma capsulatum. All
      patients with a bone marrow culture positive for MAC had a CD4 count of 20
      cells/mm3 or less. The mean CD4 count in this group (+/-95% confidence interval)
      (8+/-3 cells/mm3) was lower than that of culture-negative cases (41+/-25
      cells/mm3); P <0.015). When bone marrow cultures and mycobacterial blood cultures
      were concurrently obtained, results were usually in agreement between the two
      sites. The mean time until the report of positive mycobacterial bone marrow
      cultures (22+/-5 days) was similar to that for blood cultures (24+/-3 days). Most
      (84%) patients with multiple mycobacterial cultures had completely concordant
      results (all positive or all negative). When blood or bone marrow culture yielded
      mycobacteria, only 29% of the corresponding bone marrow examinations revealed
      stainable acid-fast bacilli (AFB). In contrast, all 3 cases with positive fungal
      bone marrow cultures also had stainable organisms on histologic examination.
      CONCLUSIONS: The combined use of bone marrow biopsy and culture as well as blood
      cultures provide the maximum diagnostic yield when evaluating patients with AIDS
      for mycobacterial or fungal infections. However, when mycobacterial infections
      were diagnosed, bone marrow results seldom provided more immediate or specific
      information than lysis centrifugation blood cultures. A single lysis
      centrifugation blood culture should be the first step in the routine evaluation
      of HIV-infected patients when disseminated MAC infection is suspected.

PMID- 9528730
TI  - Constitutional symptoms and health-related quality of life in patients with
      symptomatic HIV disease.
AB  - PURPOSE: To assess the severity of constitutional symptoms in persons with human
      immunodeficiency virus (HIV) infection, and their relationship to health-related
      quality of life (HRQOL). PATIENTS AND METHODS: Two hundred five HIV-infected
      patients (93% male, 26% African American, 28% Latino, 39% white, 7% other
      ethnicity) with diarrhea, fever, or weight loss were studied at a county hospital
      and a Veterans Administration hospital in southern California. Consenting
      subjects were administered a battery that included 11 scales measuring various
      aspects of health-related quality of life and detailed questions about six
      constitutional symptoms or symptom complexes (myalgias, exhaustion,
      anorexia/nausea/vomiting, night sweats, fever, and weight loss) as well as about
      other manifestations of HIV disease. RESULTS: Constitutional symptoms except
      weight loss were all strongly related to all measures of quality of life. On 0
      (worst) to 100 (best) point scales, mean scores ranged from 34 (for individuals
      having all five symptoms other than weight loss) to 78 (for those with none) for
      physical function, 43 to 79 for emotional well-being, and 36 to 73 for social
      function. Adjustment for helper T-lymphocyte counts, duration of illness, and
      demographic characteristics did not diminish these associations. CONCLUSION: The
      presence, number, and severity of constitutional symptoms in HIV disease is
      strongly related to health-related quality of life in symptomatic HIV-infected
      individuals. Identifying and treating these very common symptoms has the
      potential to improve quality of life in these patients.

PMID- 9528731
TI  - A randomized trial of the effects of atorvastatin and niacin in patients with
      combined hyperlipidemia or isolated hypertriglyceridemia. Collaborative
      Atorvastatin Study Group.
AB  - BACKGROUND: To assess the lipid-lowering effects and safety of atorvastatin and
      niacin in patients with combined hyperlipidemia or isolated hypertriglyceridemia.
      METHODS: We performed a randomized, open-label, parallel-design, active
      controlled, study in eight centers in the United States. We enrolled 108 patients
      with total cholesterol (TC) of > or =200 mg/dL, serum triglycerides (TG) > or
      =200 and < or =800 mg/dL, and apolipoprotein B (apo B) > or =110 mg/dL. Patients
      were randomly assigned to receive atorvastatin 10 mg once daily (n=55) or
      immediate-release niacin 1 g three times daily for 12 weeks (n=53). Patients were
      stratified based on low-density lipoprotein cholesterol (LDL-C): Patients with
      LDL-C > or =135 mg/dL were considered to have combined hyperlipidemia and
      patients with LDL-C <135 mg/dL were considered to have isolated
      hypertriglyceridemia. The primary outcome measure was percent change from
      baseline in LDL-C. Other lipid levels were evaluated as secondary parameters.
      RESULTS: Atorvastatin reduced LDL-C 30% and TC 26% from baseline, and increased
      high-density lipoprotein cholesterol (HDL-C) 4%. Total TG were reduced 17%.
      Niacin reduced LDL-C 2%, TC 7%, increased HDL-C 25%, and reduced total TG 29%
      from baseline. There was a significant difference in LDL-C reduction, the primary
      efficacy parameter, between the two treatment groups (P <0.05, favoring
      atorvastatin), as well as a significant difference in the improvement in HDL-C (P
      <0.05, favoring niacin). The effect of atorvastatin was relatively consistent
      between patients with combined hyperlipidemia and isolated hypertriglyceridemia,
      whereas there was more variability between these strata in the niacin treatment
      group. Atorvastatin was better tolerated than niacin. CONCLUSION: Atorvastatin
      may allow patients with combined hyperlipidemia to be treated with monotherapy
      and offers an efficacious and well-tolerated alternative to niacin for the
      treatment of patients with isolated hypertriglyceridemia.

PMID- 9528732
TI  - Transient abnormalities in serum bilirubin and lactate dehydrogenase levels
      following red blood cell transfusions in adults.
AB  - BACKGROUND: The effect of transfusion of small amounts of packed red blood cells
      (PRBC) on serum chemistry values is not known. METHODS: We studied 73 adult
      patients without evidence of bleeding who received 2-unit PRBC transfusions. In
      study 1 (n=39), we examined multiple laboratory values pretransfusion and 15
      minutes, 1 hour, 2 hours, and 24 hours posttransfusion. In study 2 (n=34), we
      examined changes in fractionated bilirubin, lactate dehydrogenase, and
      haptoglobin prior to and 1 hour following the transfusion. RESULTS: Total
      bilirubin increased from a median pretransfusion baseline of 0.7 mg/dL to 1.4
      mg/dL shortly after transfusion (P <0.0005), and then returned to normal 24 hours
      later. Of the 36 patients with normal pretreatment total bilirubin levels, 17
      (47%) became transiently abnormal. The lactate dehydrogenase level increased
      similarly 15 minutes after transfusion, but returned to baseline 24 hours later.
      The unconjugated bilirubin level increased from a median baseline pretransfusion
      value of 0.3 mg/dL to 1.1 mg/dL at 1 hour posttransfusion (P <0.0005). No
      significant changes were noted in conjugated bilirubin levels or haptoglobin
      concentration following transfusion. CONCLUSIONS: Transient increases in serum
      bilirubin and lactate dehydrogenase are seen following transfusion of PRBC. These
      data should be considered when interpreting laboratory values during the first
      few hours after a transfusion.

PMID- 9528733
TI  - Anticoagulation for nonvalvular atrial fibrillation: effects of type of practice
      on physicians' self-reported behavior.
AB  - BACKGROUND: This study examines whether social and economic factors affect
      physician practice and attitude with regard to warfarin anticoagulation in
      patients with nonvalvular atrial fibrillation. METHODS: We identified physicians
      in Baltimore City, Baltimore County, and Prince George's County who (1) had
      written one or more prescriptions for a digitalis compound during the preceding
      year, and (2) were classified as general practitioners, family practice
      specialists, internists, or cardiologists. All 358 physicians fulfilling these
      criteria were surveyed by questionnaire. RESULTS: The overall response rate was
      43%. Physicians who wrote 15% or more of their digitalis prescriptions for
      Medicaid patients said they used warfarin at significantly lower rates for
      patients with nonvalvular AF than other (66% versus 79%, P <0.01). The opposite
      pattern was seen with regard to aspirin. There were no significant differences in
      practice pattern between physicians located in urban vs. suburban counties.
      CONCLUSION: In our sample, self-reported anticoagulant practices for patients
      with nonvalvular AF were associated with the percentage of digitalis
      prescriptions written for Medicaid patients. In this metropolitan area,
      anticoagulant therapy was reportedly prescribed for approximately 75% of patients
      with nonvalvular atrial fibrillation.

PMID- 9528734
TI  - History-taking and preventive medicine skills among primary care physicians: an
      assessment using standardized patients.
AB  - BACKGROUND: The ability of primary care physicians to obtain important clinical
      information in initial encounters with new patients is a core competency that has
      received little attention in previous studies. This paper describes the history
      taking and preventive screening skills of practicing primary care physicians in
      initial interactions with ambulatory patients, as determined by a large panel of
      standardized patients. METHODS: Standardized patient cases with diverse
      presentations were developed and used to assess the clinical skills of 134
      primary care physicians from five Northwest states. Scoring categories for each
      case identified the percentage and content of essential history items and
      preventive screening items performed. Physicians' scores were compared by
      training and practice characteristics. RESULTS: Physicians asked 59% of essential
      history items. They frequently obtained appropriate information about presenting
      symptoms and medications, but they often missed important information about
      related symptoms and medical history. Physicians frequently screened for smoking
      and alcohol use, but rarely asked about recreational drug use. Although board
      certified general internists performed more comprehensive histories than board
      certified family practitioners in the same amount of time, both groups of
      providers missed a large number of items that should have been influential in
      developing diagnostic and treatment plans. CONCLUSIONS: Primary care physicians
      may miss important patient information in their initial interactions with
      patients. Medical intake questionnaires or other approaches should be considered
      to ensure that more complete and accurate information is available to guide
      diagnostic and treatment plans.

PMID- 9528735
TI  - A comparison of inpatient and outpatient experiences during an internal medicine
      clerkship.
AB  - PURPOSE: Our 12-week internal medicine clerkship contains an 8-week inpatient and
      a 4-week outpatient component. This study examines the differences between these
      components, comparing diagnoses seen, category of learning, and student
      contribution to patient care. METHODOLOGY: Students used logbooks to record
      diagnoses, workup, and treatment for each patient they encountered. Additionally,
      students categorized the type of learning from each encounter (ie,
      pathophysiology, evaluation/workup, treatment, differentials, patient
      education/counseling, or technical skills) and ranked their involvement in
      patient care using a 1 to 5 scale (1=little; 5=significant). Comparison of
      inpatient and outpatient data was made using chi-square analysis or Student's t
      test. RESULTS: One thousand three-hundred twenty-four patient encounters were
      analyzed (597 inpatient; 727 outpatient). The top 10 diagnoses in each setting
      were markedly different. Students reported that patient encounters in the
      inpatient setting were more likely to have involved learning about disease
      pathophysiology (21% inpatient vs 15% outpatient; P <0.001) whereas in outpatient
      encounters, students reported that they learned more about education/counseling
      (6% inpatient vs 11% outpatient; P <0.0001) and evaluation/workup (10% inpatient
      vs 15% outpatient; P <0.0001). Students' perception of their involvement in
      patient care did not differ significantly between the 2 settings (mean rank
      inpatient 3.69+/-0.87; mean rank outpatient 3.75+/-0.85; P=0.95). CONCLUSION:
      Despite spending less time with each patient during outpatient encounters,
      students considered their contribution to patient care equally significant to
      that for inpatients, suggesting that students have an active role in both
      settings.

PMID- 9528736
TI  - Restoring function in failing hearts: the effects of beta blockers.
AB  - Until recently, clinical management of congestive heart failure was purely
      palliative. The drugs used in patients with failing hearts--digoxin,
      vasodilators, and positive inotropic agents--improved contractility, reversed
      hemodynamic abnormalities, and enhanced functional status, but they failed to
      confer a survival benefit. Indeed, the use of inotropic agents often resulted in
      excess mortality--a paradox explained in part by the pharmacological properties
      of these agents, which increase production of cAMP, the intracellular messenger
      for the beta-adrenergic system. The short-term pharmacological benefits of these
      drugs may be offset by deleterious long-term biological effects on the heart
      muscle itself. The use of beta-blockers in heart failure is counterintuitive,
      given that their initial pharmacological effect is to reduce heart rate and
      contractility in a faltering heart, thus producing an effect diametrically
      opposed to that of inotropic agents. However, it is becoming more clear that beta
      blocker therapy in patients with heart failure not only improves left ventricular
      function, but may actually reverse pathological remodeling in the heart.
      Accumulating clinical evidence indicates that these beneficial changes are the
      result of secondary biological changes in the myocardium rather than a response
      to the pharmacological effects of the drugs themselves. Mounting evidence suggest
      that these agents may prolong survival in patients with heart failure, and
      ongoing clinical trials may soon confirm these preliminary findings.

PMID- 9528737
TI  - Harmless herbs? A review of the recent literature.
AB  - Herbal medicines have become a popular form of therapy. They are often perceived
      as being natural and therefore harmless. This article reviews the recent
      literature on the adverse effects of herbal remedies. Examples of allergic
      reactions, toxic reactions, adverse effects related to an herb's desired
      pharmacological actions, possible mutagenic effects, drug interactions, drug
      contamination, and mistaken plant identities are provided. Because of
      underreporting, our present knowledge may well be just the "tip of the iceberg."
      Little is known about the relative safety of herbal remedies compared to
      synthetic drug treatments, although for some herbal remedies, the risks may be
      less than for conventional drugs.

PMID- 9528738
TI  - Selectivity and toxicity of antiarrhythmic drugs: molecular interactions with ion
      channels.

PMID- 9528739
TI  - Reactive hemophagocytic syndrome associated with Penicillium marneffei infection.

PMID- 9528740
TI  - Spontaneous ecchymoses due to paroxetine administration.

PMID- 9528741
TI  - A 19-year-old woman with severe anemia.

PMID- 9528742
TI  - Glycemic control and prevalent cardiovascular disease.

PMID- 9528743
TI  - Euthanasia as an unbiased opinion.

PMID- 9528744
TI  - Euthanasia as an unbiased opinion.

PMID- 9528745
TI  - Reversible hypercapnia in COPD.

PMID- 9528746
TI  - No primary prevention by pravastatin.

PMID- 9528747
TI  - Yield of laboratory tests for case finding in the ambulatory general medical
      exam.

PMID- 9528748
TI  - Interaction between subunits of heterodimeric splicing factor U2AF is essential
      in vivo.
AB  - The heterodimeric pre-mRNA splicing factor, U2AF (U2 snRNP auxiliary factor),
      plays a critical role in 3' splice site selection. Although the U2AF subunits
      associate in a tight complex, biochemical experiments designed to address the
      requirement for both subunits in splicing have yielded conflicting results. We
      have taken a genetic approach to assess the requirement for the Drosophila U2AF
      heterodimer in vivo. We developed a novel Escherichia coli copurification assay
      to map the domain on the Drosophila U2AF large subunit (dU2AF50) that interacts
      with the Drosophila small subunit (dU2AF38). A 28-amino-acid fragment on dU2AF50
      that is both necessary and sufficient for interaction with dU2AF38 was
      identified. Using the copurification assay, we scanned this 28-amino-acid
      interaction domain for mutations that abrogate heterodimer formation. A
      collection of these dU2AF50 point mutants was then tested in vivo for genetic
      complementation of a recessive lethal dU2AF50 allele. A mutation that completely
      abolished interaction with dU2AF38 was incapable of complementation, whereas
      dU2AF50 mutations that did not effect heterodimer formation rescued the recessive
      lethal dU2AF50 allele. Analysis of heterodimer formation in embryo extracts
      derived from these interaction mutant lines revealed a perfect correlation
      between the efficiency of subunit association and the ability to complement the
      dU2AF50 recessive lethal allele. These data indicate that Drosophila U2AF
      heterodimer formation is essential for viability in vivo, consistent with a
      requirement for both subunits in splicing in vitro.

PMID- 9528750
TI  - Characterization of Stat5a and Stat5b homodimers and heterodimers and their
      association with the glucocortiocoid receptor in mammary cells.
AB  - The lactogenic hormones, i.e., prolactin and glucocorticoids, act in concert to
      stimulate transcription factors responsible for hormone-dependent milk protein
      gene expression. In the mammary gland, prolactin activates Stat5a and Stat5b and
      glucocorticoids activate the glucocorticoid receptor (GR). Immunoprecipitation
      experiments revealed that in mammary cells, Stat5a, Stat5b, and the GR are
      physically associated in vivo. The association is not dependent on lactogenic
      hormone treatment and is evident at all stages of mammary gland development.
      Immunodepletion experiments indicated that a fraction of GR and Stat5 proteins
      are not associated, suggesting that there are different intracellular pools of
      these proteins. Lactogenic hormone treatment of HC11 mammary cells resulted in
      tyrosine phosphorylation of Stat5a and Stat5b, dimerization, and rapid nuclear
      translocation of both Stat5 proteins. Following hormone treatment, Stat5a-Stat5b
      heterodimers were detected by their coimmunoprecipitation. In addition,
      immunodepletion experiments followed by gel shift analyses revealed the presence
      of active Stat5a and Stat5b homodimers. In mammary cells, Stat5b homodimers are
      less abundant than Stat5a homodimers. Although the GR does not bind the Stat5 DNA
      binding site directly, it could be detected with the Stat5-DNA complex. These
      results suggest that glucocorticoids affect milk protein gene expression via
      association of the GR with Stat5. Thus, there is a functional coupling between
      Stat-dependent and nuclear hormone receptor-dependent gene transcription.

PMID- 9528749
TI  - SWI-SNF complex participation in transcriptional activation at a step subsequent
      to activator binding.
AB  - The SWI-SNF complex in yeast and related complexes in higher eukaryotes have been
      implicated in assisting gene activation by overcoming the repressive effects of
      chromatin. We show that the ability of the transcriptional activator GAL4 to bind
      to a site in a positioned nucleosome is not appreciably impaired in swi mutant
      yeast cells. However, chromatin remodeling that depends on a transcriptional
      activation domain shows a considerable, although not complete, SWI-SNF
      dependence, suggesting that the SWI-SNF complex exerts its major effect at a step
      subsequent to activator binding. We tested this idea further by comparing the SWI
      SNF dependence of a reporter gene based on the GAL10 promoter, which has an
      accessible upstream activating sequence and a nucleosomal TATA element, with that
      of a CYC1-lacZ reporter, which has a relatively accessible TATA element. We found
      that the GAL10-based reporter gene showed a much stronger SWI-SNF dependence than
      did the CYC1-lacZ reporter with several different activators. Remarkably,
      transcription of the GAL10-based reporter by a GAL4-GAL11 fusion protein showed a
      nearly complete requirement for the SWI-SNF complex, strongly suggesting that SWI
      SNF is needed to allow access of TFIID or the RNA polymerase II holoenzyme. Taken
      together, our results demonstrate that chromatin remodeling in vivo can occur by
      both SWI-SNF-dependent and -independent avenues and suggest that the SWI-SNF
      complex exerts its major effect in transcriptional activation at a step
      subsequent to transcriptional activator-promoter recognition.

PMID- 9528751
TI  - Inactivation of p16 in human mammary epithelial cells by CpG island methylation.
AB  - Proliferation of human mammary epithelial cells (HMEC) is limited to a few
      passages in culture due to an arrest in G1 termed selection or mortality stage 0,
      M0. A small number of cells spontaneously escape M0, continue to proliferate in
      culture, and then enter a second mortality stage, M1, at which they senesce.
      Evidence that M0 involves the Rb pathway comes from the observation that
      expression of human papillomavirus type 16 E7 alleviates the M0 proliferation
      block, and we further show that the Rb-binding region of E7 is required to allow
      cells to bypass M0. In contrast, E6 does not prevent HMEC from entering M0 but,
      rather, is involved in M1 bypass. Here we show that inactivation of the D-type
      cyclin-dependent kinase inhibitor p16INK4A is associated with escape from the M0
      proliferation block. Early-passage HMEC express readily detectable amounts of p16
      protein, whereas normal or E6-expressing HMEC that escaped M0 expressed markedly
      reduced amounts of p16 mRNA and protein. This initial reduction of p16 expression
      was associated with limited methylation of the p16 promoter region CpG island. At
      later passages, a further reduction in p16 expression occurred, accompanied by
      increased CpG island methylation. In contrast, reduction of p16 expression did
      not occur in E7-expressing HMEC that bypassed M0, due to inactivation of Rb.
      These observations in the E6-expressing HMEC correlate well with the finding that
      CpG island methylation is a mechanism of p16 inactivation in the development of
      human tumors, including breast cancer.

PMID- 9528752
TI  - Protein kinase B activation and lamellipodium formation are independent
      phosphoinositide 3-kinase-mediated events differentially regulated by endogenous
      Ras.
AB  - Regulation of phosphoinositide 3-kinase (PI 3-kinase) can occur by binding of the
      regulatory p85 subunit to tyrosine-phosphorylated proteins and by binding of the
      p110 catalytic subunit to activated Ras. However, the way in which these
      regulatory mechanisms act to regulate PI 3-kinase in vivo is unclear. Here we
      show that several growth factors (basic fibroblast growth factor [bFGF], platelet
      derived growth factor [PDGF], and epidermal growth factor [EGF; to activate an
      EGF receptor-Ret chimeric receptor]) all activate PI 3-kinase in vivo in the
      neuroectoderm-derived cell line SKF5. However, these growth factors differ in
      their ability to activate PI 3-kinase-dependent signaling. PDGF and EGF(Ret)
      treatment induced PI 3-kinase-dependent lamellipodium formation and protein
      kinase B (PKB) activation. In contrast, bFGF did not induce lamellipodium
      formation but activated PKB, albeit to a small extent. PDGF and EGF(Ret)
      stimulation resulted in binding of p85 to tyrosine-phosphorylated proteins and
      strong Ras activation. bFGF, however, induced only strong activation of Ras. In
      addition, while RasAsn17 abolished bFGF activation of PKB, PDGF- and EGF(Ret)
      induced PKB activation was only partially inhibited and lamellipodium formation
      was unaffected. Interestingly, in contrast to activation of only endogenous Ras
      (bFGF), ectopic expression of activated Ras did result in lamellipodium
      formation. From this we conclude that, in vivo, p85 and Ras synergize to activate
      PI 3-kinase and that strong activation of only endogenous Ras exerts a small
      effect on PI 3-kinase activity, sufficient for PKB activation but not
      lamellipodium formation. This differential sensitivity to PI 3-kinase activation
      could be explained by our finding that PKB activation and lamellipodium formation
      are independent PI 3-kinase-induced events.

PMID- 9528753
TI  - Mechanisms of cyclin-dependent kinase inactivation by progestins.
AB  - The steroid hormone progesterone regulates proliferation and differentiation in
      the mammary gland and uterus by cell cycle phase-specific actions. In breast
      cancer cells the predominant effect of synthetic progestins is long-term growth
      inhibition and arrest in G1 phase. Progestin-mediated growth arrest of T-47D
      breast cancer cells was preceded by inhibition of cyclin D1-Cdk4, cyclin D3-Cdk4,
      and cyclin E-Cdk2 kinase activities in vitro and reduced phosphorylation of pRB
      and p107. This was accompanied by decreases in the expression of cyclins D1, D3,
      and E, decreased abundance of cyclin D1- and cyclin D3-Cdk4 complexes, increased
      association of the cyclin-dependent kinase (CDK) inhibitor p27 with the remaining
      Cdk4 complexes, and changes in the molecular masses and compositions of cyclin E
      complexes. In control cells cyclin E eluted from Superdex 200 as two peaks of
      approximately 120 and approximately 200 kDa, with the 120-kDa peak displaying
      greater cyclin E-associated kinase activity. Following progestin treatment,
      almost all of the cyclin E was in the 200-kDa, low-activity form, which was
      associated with the CDK inhibitors p21 and p27; this change preceded the
      inhibition of cell cycle progression. These data suggest preferential formation
      of this higher-molecular-weight, CDK inhibitor-bound form and a reduced number of
      cyclin E-Cdk2 complexes as mechanisms for the decreased cyclin E-associated
      kinase activity following progestin treatment. Ectopic expression of cyclin D1 in
      progestin-inhibited cells led to the reappearance of the 120-kDa active form of
      cyclin E-Cdk2 preceding the resumption of cell cycle progression. Thus, decreased
      cyclin expression and consequent increased CDK inhibitor association are likely
      to mediate the decreases in CDK activity accompanying progestin-mediated growth
      inhibition.

PMID- 9528755
TI  - Multiple developmental requirements of noisette, the Drosophila homolog of the U2
      snRNP-associated polypeptide SP3a60.
AB  - We report the cloning of the noisette gene (noi), which encodes the Drosophila
      melanogaster ortholog of a U2 snRNP-associated splicing factor, SF3a60 (SAP61) in
      humans and PRP9p in Saccharomyces cerevisiae. Antibodies raised against human
      SF3a60 recognized NOI in flies, showing a nuclear localization in all the stages
      examined, including the embryo, the dividing cells of imaginal discs, and the
      larval polyploid nuclei. NOI is expressed in somatic and germinal cells of both
      male and female gonads. By mobilization of P transposons, we have generated a
      large number of noi mutations. Complete loss of function resulted in lethality at
      the end of embryogenesis, without obvious morphological defects. Hypomorphic
      alleles revealed multiple roles of noi for the survival and differentiation of
      male germ cells, the differentiation of female germ cells, and the development of
      several adult structures.

PMID- 9528754
TI  - Functional interactions between yeast mitochondrial ribosomes and mRNA 5'
      untranslated leaders.
AB  - Translation of mitochondrial mRNAs in Saccharomyces cerevisiae depends on mRNA
      specific translational activators that recognize the 5' untranslated leaders (5'
      UTLs) of their target mRNAs. We have identified mutations in two new nuclear
      genes that suppress translation defects due to certain alterations in the 5'-UTLs
      of both the COX2 and COX3 mRNAs, indicating a general function in translational
      activation. One gene, MRP21, encodes a protein with a domain related to the
      bacterial ribosomal protein S21 and to unidentified proteins of several animals.
      The other gene, MRP51, encodes a novel protein whose only known homolog is
      encoded by an unidentified gene in S. kluyveri. Deletion of either MRP21 or MRP51
      completely blocked mitochondrial gene expression. Submitochondrial fractionation
      showed that both Mrp21p and Mrp51p cosediment with the mitochondrial ribosomal
      small subunit. The suppressor mutations are missense substitutions, and those
      affecting Mrp21p alter the region homologous to E. coli S21, which is known to
      interact with mRNAs. Interactions of the suppressor mutations with leaky
      mitochondrial initiation codon mutations strongly suggest that the suppressors do
      not generally increase translational efficiency, since some alleles that strongly
      suppress 5'-UTL mutations fail to suppress initiation codon mutations. We propose
      that mitochondrial ribosomes themselves recognize a common feature of mRNA 5'
      UTLs which, in conjunction with mRNA-specific translational activation, is
      required for organellar translation initiation.

PMID- 9528756
TI  - Anisomycin selectively desensitizes signalling components involved in stress
      kinase activation and fos and jun induction.
AB  - Anisomycin, a translational inhibitor secreted by Streptomyces spp., strongly
      activates the stress-activated mitogen-activated protein (MAP) kinases JNK/SAPK
      (c-Jun NH2-terminal kinase/stress-activated protein kinase) and p38/RK in
      mammalian cells, resulting in rapid induction of immediate-early (IE) genes in
      the nucleus. Here, we have characterized this response further with respect to
      homologous and heterologous desensitization of IE gene induction and stress
      kinase activation. We show that anisomycin acts exactly like a signalling agonist
      in eliciting highly specific and virtually complete homologous desensitization.
      Anisomycin desensitization of a panel of IE genes (c-fos, fosB, c-jun, junB, and
      junD), using epidermal growth factor (EGF), basic fibroblast growth factor,
      (bFGF), tumor necrosis factor alpha (TNF-alpha), anisomycin, tetradecanoyl
      phorbol acetate (TPA), and UV radiation as secondary stimuli, was found to be
      extremely specific both with respect to the secondary stimuli and at the level of
      individual genes. Further, we show that anisomycin-induced homologous
      desensitization is caused by the fact that anisomycin no longer activates the
      JNK/SAPK and p38/RK MAP kinase cascades in desensitized cells. In anisomycin
      desensitized cells, activation of JNK/SAPKs by UV radiation and hyperosmolarity
      is almost completely lost, and that of the p38/RK cascade is reduced to about 50%
      of the normal response. However, all other stimuli produced normal or augmented
      activation of these two kinase cascades in anisomycin-desensitized cells. These
      data show that anisomycin behaves like a true signalling agonist and suggest that
      the anisomycin-desensitized signalling component(s) is not involved in JNK/SAPK
      or p38/RK activation by EGF, bFGF, TNF-alpha, or TPA but may play a significant
      role in UV- and hyperosmolarity-stimulated responses.

PMID- 9528757
TI  - Dbp6p is an essential putative ATP-dependent RNA helicase required for 60S
      ribosomal-subunit assembly in Saccharomyces cerevisiae.
AB  - A previously uncharacterized Saccharomyces cerevisiae open reading frame,
      YNR038W, was analyzed in the context of the European Functional Analysis Network.
      YNR038W encodes a putative ATP-dependent RNA helicase of the DEAD-box protein
      family and was therefore named DBP6 (DEAD-box protein 6). Dbp6p is essential for
      cell viability. In vivo depletion of Dbp6p results in a deficit in 60S ribosomal
      subunits and the appearance of half-mer polysomes. Pulse-chase labeling of pre
      rRNA and steady-state analysis of pre-rRNA and mature rRNA by Northern
      hybridization and primer extension show that Dbp6p depletion leads to decreased
      production of the 27S and 7S precursors, resulting in a depletion of the mature
      25S and 5.8S rRNAs. Furthermore, hemagglutinin epitope-tagged Dbp6p is detected
      exclusively within the nucleolus. We propose that Dbp6p is required for the
      proper assembly of preribosomal particles during the biogenesis of 60S ribosomal
      subunits, probably by acting as an rRNA helicase.

PMID- 9528759
TI  - Identification and analysis of Mot3, a zinc finger protein that binds to the
      retrotransposon Ty long terminal repeat (delta) in Saccharomyces cerevisiae.
AB  - Spt3 and Mot1 are two transcription factors of Saccharomyces cerevisiae that are
      thought to act in a related fashion to control the function of TATA-binding
      protein (TBP). Current models suggest that while Spt3 and Mot1 do not directly
      interact, they do function in a related fashion to stabilize the TBP-TATA
      interaction at particular promoters. Consistent with this model, certain
      combinations of spt3 and mot1 mutations are inviable. To identify additional
      proteins related to Spt3 and Mot1 functions, we screened for high-copy-number
      suppressors of the mot1 spt3 inviability. This screen identified a previously
      unstudied gene, MOT3, that encodes a zinc finger protein. We show that Mot3 binds
      in vitro to three sites within the retrotransposon Ty long terminal repeat
      (delta) sequence. One of these sites is immediately 5' of the delta TATA region.
      Although a mot3 null mutation causes no strong phenotypes, it does cause some
      mild phenotypes, including a very modest increase in Ty mRNA levels, partial
      suppression of transcriptional defects caused by a mot1 mutation, and partial
      suppression of an spt3 mutation. These results, in conjunction with those of an
      independent study of Mot3 (A. Grishin, M. Rothenberg, M. A. Downs, and K. J.
      Blumer, Genetics, in press), suggest that this protein plays a varied role in
      gene expression that may be largely redundant with other factors.

PMID- 9528758
TI  - Rex-1, a gene encoding a transcription factor expressed in the early embryo, is
      regulated via Oct-3/4 and Oct-6 binding to an octamer site and a novel protein,
      Rox-1, binding to an adjacent site.
AB  - The Rex-1 (Zfp-42) gene, which encodes an acidic zinc finger protein, is
      expressed at high levels in embryonic stem (ES) and F9 teratocarcinoma cells.
      Prior analysis identified an octamer motif in the Rex-1 promoter which is
      required for promoter activity in undifferentiated F9 cells and is involved in
      retinoic acid (RA)-associated reduction in expression. We show here that the Oct
      3/4 transcription factor, but not Oct-1, can either activate or repress the Rex-1
      promoter, depending on the cellular environment. Rex-1 repression is enhanced by
      E1A. The protein domain required for Oct-3/4 activation was mapped to amino acids
      1 to 35, whereas the domain required for Oct-3/4 repression was mapped to amino
      acids 61 to 126, suggesting that the molecular mechanisms underlying
      transcriptional activation and repression differ. Like Oct-3/4, Oct-6 can also
      lower the expression of the Rex-1 promoter via the octamer site, and the amino
      terminal portion of Oct-6 mediates this repression. In addition to the octamer
      motif, a novel positive regulatory element, located immediately 5' of the octamer
      motif, was identified in the Rex-1 promoter. Mutations in this element greatly
      reduce Rex-1 promoter activity in F9 cells. High levels of a binding protein(s),
      designated Rox-1, recognize this novel DNA element in F9 cells, and this binding
      activity is reduced following RA treatment. Taken together, these results
      indicate that the Rex-1 promoter is regulated by specific octamer family members
      in early embryonic cells and that a novel element also contributes to Rex-1
      expression.

PMID- 9528761
TI  - The absence of enhancer competition between Igf2 and H19 following transfer into
      differentiated cells.
AB  - H19 and Igf2 are reciprocally imprinted genes that lie 90 kb apart on mouse
      chromosome 7. The two genes are coexpressed during development, with the H19 gene
      expressed exclusively from the maternal chromosome and Igf2 from the paternal
      chromosome. It has been proposed that their reciprocal imprinting is governed by
      a competition between the genes for a common set of enhancers. The competition on
      the paternal chromosome is influenced by extensive allele-specific methylation of
      the H19 gene and its 5' flank, which acts to inhibit H19 transcription and thus
      indirectly leads to the activation of the Igf2 gene. In contrast, no allele
      specific methylation has been detected on the maternal chromosome, and the basis
      for the preference for H19 transcription on that chromosome is unresolved. In
      this investigation, the mechanism controlling the silencing of the Igf2 gene on
      the maternal chromosome was explored by studying the transcriptional activity of
      a yeast artificial chromosome (YAC) containing Igf2 and H19 following transfer
      into differentiated tissue culture cells. Contrary to expectations, both H19 and
      Igf2 were expressed from a single integrated copy of the YAC. Furthermore, Igf2
      expression appeared to be independent of the H19 locus, based on deletions of the
      H19 gene promoter and its enhancers. These results suggest that an active process
      is responsible for the transcriptional bias toward H19 on the maternal chromosome
      and that the hypomethylated state of this chromosome cannot be viewed as a
      "default" state. Moreover, the active process is not reproduced in a
      differentiated cell and may require passage through the female germ line.

PMID- 9528760
TI  - Requirement for end-joining and checkpoint functions, but not RAD52-mediated
      recombination, after EcoRI endonuclease cleavage of Saccharomyces cerevisiae DNA.
AB  - RAD52 and RAD9 are required for the repair of double-strand breaks (DSBs) induced
      by physical and chemical DNA-damaging agents in Saccharomyces cerevisiae.
      Analysis of EcoRI endonuclease expression in vivo revealed that, in contrast to
      DSBs containing damaged or modified termini, chromosomal DSBs retaining
      complementary ends could be repaired in rad52 mutants and in G1-phase Rad+ cells.
      Continuous EcoRI-induced scission of chromosomal DNA blocked the growth of rad52
      mutants, with most cells arrested in G2 phase. Surprisingly, rad52 mutants were
      not more sensitive to EcoRI-induced cell killing than wild-type strains. In
      contrast, endonuclease expression was lethal in cells deficient in Ku-mediated
      end joining. Checkpoint-defective rad9 mutants did not arrest cell cycling and
      lost viability rapidly when EcoRI was expressed. Synthesis of the endonuclease
      produced extensive breakage of nuclear DNA and stimulated interchromosomal
      recombination. These results and those of additional experiments indicate that
      cohesive ended DSBs in chromosomal DNA can be accurately repaired by RAD52
      mediated recombination and by recombination-independent complementary end joining
      in yeast cells.

PMID- 9528762
TI  - A differential screen for ligand-regulated genes: identification of HoxA10 as a
      target of vitamin D3 induction in myeloid leukemic cells.
AB  - 1,25-Dihydroxyvitamin D3 [1,25(OH)2D3], the hormonal ligand for vitamin D3, is a
      potent inducer of myeloid-leukemic-cell differentiation. Such cells differentiate
      exclusively into monocytes/macrophages in response to this ligand. Since
      1,25(OH)2D3 transduces its hormone signal through the vitamin D3 receptor (VDR),
      a ligand-modulated transcription factor and member of the nuclear hormone
      receptor superfamily, we sought to identify direct VDR target genes induced
      during this differentiation process. To do so, we applied a modified differential
      screen with a nascent-RNA purification strategy using biases for immediate-early
      response genes induced by 1,25(OH)2D3 in the myelomonocytic cell line U937. Using
      this screen, we had previously identified p21Waf1/Cip1 as a gene
      transcriptionally induced by 1,25(OH)2D3 and demonstrated that this induction
      facilitates the differentiation of U937 cells into monocytes/macrophages (24).
      Here, we describe in detail our differential screen strategy and the
      identification and isolation of 20 1,25(OH)2D3-inducible genes or unknown cDNAs
      by means of this screen. One gene newly identified as a target of VDR regulation
      in myeloid cells is the homeobox HoxA10 gene. HoxA10 protein may act as a general
      regulator of cell growth, since overexpression of HoxA10 facilitated the
      differentiation of U937 cells into monocytes/macrophages independent of
      1,25(OH)2D3 and acted to strongly inhibit the growth of the breast cancer cell
      line MCF-7 by arresting these cells in G1.

PMID- 9528763
TI  - Hepatitis delta virus RNA editing is highly specific for the amber/W site and is
      suppressed by hepatitis delta antigen.
AB  - RNA editing at adenosine 1012 (amber/W site) in the antigenomic RNA of hepatitis
      delta virus (HDV) allows two essential forms of the viral protein, hepatitis
      delta antigen (HDAg), to be synthesized from a single open reading frame. Editing
      at the amber/W site is thought to be catalyzed by one of the cellular enzymes
      known as adenosine deaminases that act on RNA (ADARs). In vitro, the enzymes
      ADAR1 and ADAR2 deaminate adenosines within many different sequences of base
      paired RNA. Since promiscuous deamination could compromise the viability of HDV,
      we wondered if additional deamination events occurred within the highly base
      paired HDV RNA. By sequencing cDNAs derived from HDV RNA from transfected Huh-7
      cells, we determined that the RNA was not extensively modified at other
      adenosines. Approximately 0.16 to 0.32 adenosines were modified per antigenome
      during 6 to 13 days posttransfection. Interestingly, all observed non-amber/W
      adenosine modifications, which occurred mostly at positions that are highly
      conserved among naturally occurring HDV isolates, were found in RNAs that were
      also modified at the amber/W site. Such coordinate modification likely limits
      potential deleterious effects of promiscuous editing. Neither viral replication
      nor HDAg was required for the highly specific editing observed in cells. However,
      HDAg was found to suppress editing at the amber/W site when expressed at levels
      similar to those found during HDV replication. These data suggest HDAg may
      regulate amber/W site editing during virus replication.

PMID- 9528764
TI  - Estrogen response elements function as allosteric modulators of estrogen receptor
      conformation.
AB  - The estrogen receptor (ER) is a ligand-dependent transcription factor that
      regulates the expression of estrogen-responsive genes. ER-mediated
      transcriptional changes are brought about by interaction of the ER with the
      estrogen response element (ERE). In this study, we examined the interaction of
      the Xenopus laevis ER DNA binding domain (DBD) and the intact ER with the X.
      laevis vitellogenin A2 ERE and the human pS2 ERE. Using gel mobility shift, DNase
      I footprinting, and methylation interference assays, we demonstrated that the DBD
      bound only as a dimer to the A2 ERE. However, the DBD bound as a monomer to the
      consensus pS2 ERE half site at lower DBD concentrations and then as a homodimer
      to the consensus and imperfect pS2 ERE half site at higher DBD concentrations.
      Antibody supershift experiments carried out with partially purified, yeast
      expressed full-length ER demonstrated that three ER-specific antibodies
      interacted differentially with A2 and pS2 ERE-bound ER, indicating that receptor
      epitopes were differentially exposed. Furthermore, partial digestion of the A2
      and pS2 ERE-bound ER with chymotrypsin or trypsin produced distinct protease
      cleavage patterns. Taken together, these data provide evidence that differential
      interaction of the DBD with the A2 and pS2 EREs brings about global changes in ER
      conformation. The conformational changes in ER induced by individual ERE
      sequences could lead to association of the receptor with different transcription
      factors and assist in the differential modulation of estrogen-responsive genes in
      target cells.

PMID- 9528765
TI  - Analysis of the interaction of the novel RNA polymerase II (pol II) subunit
      hsRPB4 with its partner hsRPB7 and with pol II.
AB  - Under conditions of environmental stress, prokaryotes and lower eukaryotes such
      as the yeast Saccharomyces cerevisiae selectively utilize particular subunits of
      RNA polymerase II (pol II) to alter transcription to patterns favoring survival.
      In S. cerevisiae, a complex of two such subunits, RPB4 and RPB7, preferentially
      associates with pol II during stationary phase; of these two subunits, RPB4 is
      specifically required for survival under nonoptimal growth conditions.
      Previously, we have shown that RPB7 possesses an evolutionarily conserved human
      homolog, hsRPB7, which was capable of partially interacting with RPB4 and the
      yeast transcriptional apparatus. Using this as a probe in a two-hybrid screen, we
      have now established that hsRPB4 is also conserved in higher eukaryotes. In
      contrast to hsRPB7, hsRPB4 has diverged so that it no longer interacts with yeast
      RPB7, although it partially complements rpb4- phenotypes in yeast. However,
      hsRPB4 associates strongly and specifically with hsRPB7 when expressed in yeast
      or in mammalian cells and copurifies with intact pol II. hsRPB4 expression in
      humans parallels that of hsRPB7, supporting the idea that the two proteins may
      possess associated functions. Structure-function studies of hsRPB4-hsRPB7 are
      used to establish the interaction interface between the two proteins. This
      identification completes the set of human homologs for RNA pol II subunits
      defined in yeast and should provide the basis for subsequent structural and
      functional characterization of the pol II holoenzyme.

PMID- 9528766
TI  - Nerve growth factor activates extracellular signal-regulated kinase and p38
      mitogen-activated protein kinase pathways to stimulate CREB serine 133
      phosphorylation.
AB  - The mechanisms by which growth factor-induced signals are propagated to the
      nucleus, leading to the activation of the transcription factor CREB, have been
      characterized. Nerve growth factor (NGF) was found to activate multiple signaling
      pathways that mediate the phosphorylation of CREB at the critical regulatory
      site, serine 133 (Ser-133). NGF activates the extracellular signal-regulated
      kinase (ERK) mitogen-activated protein kinases (MAPKs), which in turn activate
      the pp90 ribosomal S6 kinase (RSK) family of Ser/Thr kinases, all three members
      of which were found to catalyze CREB Ser-133 phosphorylation in vitro and in
      vivo. In addition to the ERK/RSK pathway, we found that NGF activated the p38
      MAPK and its downstream effector, MAPK-activated protein kinase 2 (MAPKAP kinase
      2), resulting in phosphorylation of CREB at Ser-133. Inhibition of either the
      ERK/RSK or the p38/MAPKAP kinase 2 pathway only partially blocked NGF-induced
      CREB Ser-133 phosphorylation, suggesting that either pathway alone is sufficient
      for coupling the NGF signal to CREB activation. However, inhibition of both the
      ERK/RSK and the p38/MAPKAP kinase 2 pathways completely abolished NGF-induced
      CREB Ser-133 phosphorylation. These findings indicate that NGF activates two
      distinct MAPK pathways, both of which contribute to the phosphorylation of the
      transcription factor CREB and the activation of immediate-early genes.

PMID- 9528767
TI  - Interactions within the yeast Sm core complex: from proteins to amino acids.
AB  - Sm core proteins play an essential role in the formation of small nuclear
      ribonucleoprotein particles (snRNPs) by binding to small nuclear RNAs and
      participating in a network of protein interactions. The two-hybrid system was
      used to identify SmE interacting proteins and to test for interactions between
      all pairwise combinations of yeast Sm proteins. We observed interactions between
      SmB and SmD3, SmE and SmF, and SmE and SmG. For these interactions, a direct
      biochemical assay confirmed the validity of the results obtained in vivo. To map
      the protein-protein interaction surface of Sm proteins, we generated a library of
      SmE mutants and investigated their ability to interact with SmF and/or SmG
      proteins in the two-hybrid system. Several classes of mutants were observed: some
      mutants are unable to interact with either SmF or SmG proteins, some interact
      with SmG but not with SmF, while others interact moderately with SmF but not with
      SmG. Our mutational analysis of yeast SmE protein shows that conserved
      hydrophobic residues are essential for interactions with SmF and SmG as well as
      for viability. Surprisingly, we observed that other evolutionarily conserved
      positions are tolerant to mutations, with substitutions affecting binding to SmF
      and SmG only mildly and conferring a wild-type growth phenotype.

PMID- 9528768
TI  - Protein serine/threonine phosphatase Ptc2p negatively regulates the unfolded
      protein response by dephosphorylating Ire1p kinase.
AB  - Cells respond to the accumulation of unfolded proteins in the endoplasmic
      reticulum (ER) by increasing the transcription of the genes encoding ER-resident
      chaperone proteins. Ire1p is a transmembrane protein kinase that transmits the
      signal from unfolded proteins in the lumen of the ER by a mechanism that requires
      oligomerization and trans-autophosphorylation of its cytoplasmic-nucleoplasmic
      kinase domain. Activation of Ire1p induces a novel spliced form of HAC1 mRNA that
      produces Hac1p, a transcription factor that is required for activation of the
      transcription of genes under the control of the unfolded-protein response (UPR)
      element. Searching for proteins that interact with Ire1p in Saccharomyces
      cerevisiae, we isolated PTC2, which encodes a serine/threonine phosphatase of
      type 2C. The Ptc2p interaction with Ire1p is specific, direct, dependent on Ire1p
      phosphorylation, and mediated through a kinase interaction domain within Ptc2p.
      Ptc2p dephosphorylates Ire1p efficiently in an Mg2+-dependent manner in vitro.
      PTC2 is nonessential for growth and negatively regulates the UPR pathway. Strains
      carrying null alleles of PTC2 have a three- to fourfold-increased UPR and
      increased levels of spliced HAC1 mRNA. Overexpression of wild-type Ptc2p but not
      catalytically inactive Ptc2p reduces levels of spliced HAC1 mRNA and attenuates
      the UPR, demonstrating that the phosphatase activity of Ptc2p is required for
      regulation of the UPR. These results demonstrate that Ptc2p downregulates the UPR
      by dephosphorylating Ire1p and reveal a novel mechanism of regulation in the UPR
      pathway upstream of the HAC1 mRNA splicing event.

PMID- 9528769
TI  - pp90rsk1 regulates estrogen receptor-mediated transcription through
      phosphorylation of Ser-167.
AB  - The estrogen receptor alpha (ER), a member of the steroid receptor superfamily,
      contains an N-terminal hormone-independent transcriptional activation function
      (AF-1) and a C-terminal hormone-dependent transcriptional activation function (AF
      2). Here, we used in-gel kinase assays to determine that pp90rsk1 activated by
      either epidermal growth factor (EGF) or phorbol myristate acetate specifically
      phosphorylates Ser-167 within AF-1. In vitro kinase assays demonstrated that
      pp90rsk1 phosphorylates the N terminus of the wild-type ER but not of a mutant ER
      in which Ser-167 was replaced by Ala. In vivo, EGF stimulated phosphorylation of
      Ser-167 as well as Ser-118. Ectopic expression of active pp90rsk1 increased the
      level of phosphorylation of Ser-167 compared to that of either a mutant pp90rsk1,
      which is catalytically inactive in the N-terminal kinase domain, or to that of
      vector control. The ER formed a stable complex with the mutant pp90rsk1 in vivo.
      Transfection of the mutant pp90rsk1 depressed ER-dependent transcription of both
      a wild-type ER and a mutant ER that had a defective AF-2 domain (ER TAF-1).
      Furthermore, replacing either Ser-118 or Ser-167 with Ala in ER TAF-1 showed
      similar decreases in transcription levels. A double mutant in which both Ser-118
      and Ser-167 were replaced with Ala demonstrated a further decrease in
      transcription compared to either of the single mutations. Taken together, our
      results strongly suggest that pp90rsk1 phosphorylates Ser-167 of the human ER in
      vivo and that Ser-167 aids in regulating the transcriptional activity of AF-1 in
      the ER.

PMID- 9528770
TI  - Multiple and distinct activation and repression sequences mediate the regulated
      transcription of IME1, a transcriptional activator of meiosis-specific genes in
      Saccharomyces cerevisiae.
AB  - IME1 encodes a transcriptional activator required for the transcription of
      meiosis-specific genes and initiation of meiosis in Saccharomyces cerevisiae. The
      transcription of IME1 is repressed in the presence of glucose, and a low basal
      level of IME1 RNA is observed in vegetative cultures with acetate as the sole
      carbon source. Upon nitrogen depletion a transient induction in the transcription
      of IME1 is observed in MATa/MATalpha diploids but not in MAT-insufficient
      strains. In this study we demonstrate that the transcription of IME1 is
      controlled by an extremely unusual large 5' region, over 2,100 bp long. This area
      is divided into four different upstream controlling sequences (UCS). UCS2
      promotes the transcription of IME1 in the presence of a nonfermentable carbon
      source. UCS2 is flanked by three negative regions: UCS1, which exhibits URS
      activity in the presence of nitrogen, and UCS3 and UCS4, which repress the
      activity of UCS2 in MAT-insufficient cells. UCS2 consists of alternate positive
      and negative elements: three distinct constitutive URS elements that prevent the
      function of any upstream activating sequence (UAS) under all growth conditions, a
      constitutive UAS element that promotes expression under all growth conditions, a
      UAS element that is active only in vegetative media, and two discrete elements
      that function as UASs in the presence of acetate. Sequence analysis of IME1
      revealed the presence of two almost identical 30- to 32-bp repeats. Surprisingly,
      one repeat, IREd, exhibits constitutive URS activity, whereas the other repeat,
      IREu, serves as a carbon-source-regulated UAS element. The RAS-cyclic AMP
      dependent protein kinase cAPK pathway prevents the UAS activity of IREu in the
      presence of glucose as the sole carbon source, while the transcriptional
      activators Msn2p and Msn4p promote the UAS activity of this repeat in the
      presence of acetate. We suggest that the use of multiple negative and positive
      elements is essential to restrict transcription to the appropriate conditions and
      that the combinatorial effect of the entire region leads to the regulated
      transcription of IME1.

PMID- 9528771
TI  - Stat proteins control lymphocyte proliferation by regulating p27Kip1 expression.
AB  - The proliferation of lymphocytes in response to cytokine stimulation is essential
      for a variety of immune responses. Recent studies with signal transducer and
      activator of transcription 6 (Stat6)-deficient mice have demonstrated that this
      protein is required for the normal proliferation of lymphocytes in response to
      interleukin-4 (IL-4). In this report, we show that the impaired IL-4-induced
      proliferative response of Stat6-deficient lymphocytes is not due to an inability
      to activate alternate signaling pathways, such as those involving insulin
      receptor substrates, or to a failure to upregulate IL-4 receptor levels. Cell
      cycle analysis showed that the percentage of Stat6-deficient lymphocytes that
      transit from the G1 to the S phase of the cell cycle following IL-4 stimulation
      is lower than that of control lymphocytes. Although the regulation of many genes
      involved in the control of cytokine-induced proliferation is normal in Stat6
      deficient lymphocytes, protein levels of the cdk inhibitor p27Kip1 were found to
      be markedly dysregulated. p27Kip1 is expressed at significantly higher levels in
      Stat6-deficient lymphocytes than in control cells following IL-4 stimulation. The
      higher level of p27Kip1 expression seen in IL-4-stimulated Stat6-deficient
      lymphocytes correlates with decreased cdk2-associated kinase activity and is the
      result of the increased accumulation of protein rather than altered mRNA
      expression. Similarly, higher levels of p27Kip1 protein expression are also seen
      following IL-12 stimulation of Stat4-deficient lymphocytes than are seen
      following stimulation of control cells. These data suggest that Stat proteins may
      control the cytokine-induced proliferative response of activated T cells by
      regulating the expression of cell cycle inhibitors so that cyclin-cdk complexes
      may function to promote transition from the G1 to the S phase of the cell cycle.

PMID- 9528772
TI  - Differential effects of light and heat on the Drosophila circadian clock proteins
      PER and TIM.
AB  - Circadian (approximately 24-h) rhythms are governed by endogenous biochemical
      oscillators (clocks) that in a wide variety of organisms can be phase shifted
      (i.e., delayed or advanced) by brief exposure to light and changes in
      temperature. However, how changes in temperature reset circadian timekeeping
      mechanisms is not known. To begin to address this issue, we measured the effects
      of short-duration heat pulses on the protein and mRNA products from the
      Drosophila circadian clock genes period (per) and timeless (tim). Heat pulses at
      all times in a daily cycle elicited dramatic and rapid decreases in the levels of
      PER and TIM proteins. PER is sensitive to heat but not light, indicating that
      individual clock components can markedly differ in sensitivity to environmental
      stimuli. A similar resetting mechanism involving delays in the per-tim
      transcriptional-translational feedback loop likely underlies the observation that
      when heat and light signals are administered in the early night, they both evoke
      phase delays in behavioral rhythms. However, whereas previous studies showed that
      the light-induced degradation of TIM in the late night is accompanied by stable
      phase advances in the temporal regulation of the PER and TIM biochemical rhythms,
      the heat-induced degradation of PER and TIM at these times in a daily cycle
      results in little, if any, long-term perturbation in the cycles of these clock
      proteins. Rather, the initial heat-induced degradation of PER and TIM in the late
      night is followed by a transient and rapid increase in the speed of the PER-TIM
      temporal program. The net effect of these heat-induced changes results in an
      oscillatory mechanism with a steady-state phase similar to that of the
      unperturbed control situation. These findings can account for the lack of
      apparent steady-state shifts in Drosophila behavioral rhythms by heat pulses
      applied in the late night and strongly suggest that stimulus-induced changes in
      the speed of circadian clocks can contribute to phase-shifting responses.

PMID- 9528773
TI  - Activation of Src family members is not required for the platelet-derived growth
      factor beta receptor to initiate mitogenesis.
AB  - The basal activity of Src family kinases is readily detectable throughout the
      cell cycle and increases by two- to fivefold upon acute stimulation of cells with
      growth factors such as platelet-derived growth factor. Previous reports have
      demonstrated a requirement for Src activity for the G1/S and G2/M transitions.
      With a chimeric alpha-beta PDGF receptor (PDGFR) expressed in fibroblasts, we
      have investigated the importance of the PDGF-mediated increase in Src activity at
      the G0/G1 transition for subsequent cell cycle events. A mutant PDGFR chimera
      that was not able to detectably associate with or activate Src was compromised in
      its ability to mediate tyrosine phosphorylation of receptor-associated signaling
      molecules and initiated a submaximal activation of Erk. In contrast to these
      early cell cycle events, later responses such as entry of cells into S phase and
      cell proliferation proceeded normally when Src activity did not increase
      following acute stimulation with PDGF. We conclude that the initial burst of Src
      activity is required for efficient tyrosine phosphorylation of receptor
      associated proteins such as PLCgamma, RasGAP, Shc, and SHP-2 and for maximal
      activation of Erk. Surprisingly, these events are not required for PDGF-dependent
      cell proliferation. Finally, later cell cycle events do not require that Src be
      activated at the G0/G1 transition and leave open the possibility that events such
      as the G1/S transition require the basal Src activity and/or activation of Src at
      later times in G1.

PMID- 9528774
TI  - The carboxy-terminal domain of Hsc70 provides binding sites for a distinct set of
      chaperone cofactors.
AB  - The modulation of the chaperone activity of the heat shock cognate Hsc70 protein
      in mammalian cells involves cooperation with chaperone cofactors, such as Hsp40;
      BAG-1; the Hsc70-interacting protein, Hip; and the Hsc70-Hsp90-organizing
      protein, Hop. By employing the yeast two-hybrid system and in vitro interaction
      assays, we have provided insight into the structural basis that underlies Hsc70's
      cooperation with different cofactors. The carboxy-terminal domain of Hsc70,
      previously shown to form a lid over the peptide binding pocket of the chaperone
      protein, mediates the interaction of Hsc70 with Hsp40 and Hop. Remarkably, the
      two cofactors bind to the carboxy terminus of Hsc70 in a noncompetitive manner,
      revealing the existence of distinct binding sites for Hsp40 and Hop within this
      domain. In contrast, Hip interacts exclusively with the amino-terminal ATPase
      domain of Hsc70. Hence, Hsc70 possesses separate nonoverlapping binding sites for
      Hsp40, Hip, and Hop. This appears to enable the chaperone protein to cooperate
      simultaneously with multiple cofactors. On the other hand, BAG-1 and Hip have
      recently been shown to compete in binding to the ATPase domain. Our data thus
      establish the existence of a network of cooperating and competing cofactors
      regulating the chaperone activity of Hsc70 in the mammalian cell.

PMID- 9528775
TI  - Structure of nonhairpin coding-end DNA breaks in cells undergoing V(D)J
      recombination.
AB  - The V(D)J recombinase recognizes a pair of immunoglobulin or T-cell receptor gene
      segments flanked by recombination signal sequences and introduces double-strand
      breaks, generating two signal ends and two coding ends. Broken coding ends were
      initially identified as covalently closed hairpin DNA molecules. Before
      recombination, however, the hairpins must be opened and the ends must be modified
      by nuclease digestion and N-region addition. We have now analyzed nonhairpin
      coding ends associated with various immunoglobulin gene segments in cells
      undergoing V(D)J recombination. We found that these broken DNA ends have
      different nonrandom 5'-strand deletions which were characteristic for each locus
      examined. These deletions correlate well with the sequence characteristics of
      coding joints involving these gene segments. In addition, unlike broken signal
      ends, these nonhairpin coding-end V(D)J recombination reaction intermediates have
      3' overhanging ends. We discuss the implications of these results for models of
      how sequence modifications occur during coding-joint formation.

PMID- 9528776
TI  - A heat-sensitive Arabidopsis thaliana kinase substitutes for human p70s6k
      function in vivo.
AB  - In mammalian cells, mitogen-induced phosphorylation of ribosomal protein S6 by
      p70s6k has been implicated in the selective translational upregulation of 5'TOP
      mRNAs. We demonstrate here that the homologous Arabidopsis thaliana protein,
      AtS6k2, ectopically expressed in human 293 cells or isolated from plant cells,
      phosphorylates specifically mammalian and plant S6 at 25 degrees C but not at 37
      degrees C. When Arabidopsis suspension culture cells are shifted from 25 to 37
      degrees C, the kinase becomes rapidly inactivated, consistent with the
      observation that heat shock abrogates S6 phosphorylation in plants. Treatment
      with potato acid phosphatase reduced the specific activity of immunoprecipitated
      AtS6k2 threefold, an effect which was blocked in the presence of 4-nitrophenyl
      phosphate. In quiescent mammalian cells, AtS6k2 is activated by serum
      stimulation, a response which is abolished by the fungal metabolite wortmannin
      but is resistant to rapamycin. Treatment of mammalian cells with rapamycin
      abolishes in vivo S6 phosphorylation by p70s6k; however, ectopic expression of
      AtS6k2 rescues the rapamycin block. Collectively, the data demonstrate that
      AtS6k2 is the functional plant homolog of mammalian p70s6k and identify a new
      signalling pathway in plants.

PMID- 9528777
TI  - Expansions and contractions in a tandem repeat induced by double-strand break
      repair.
AB  - Repair of a double-strand break (DSB) in yeast can induce very frequent
      expansions and contractions in a tandem array of 375-bp repeats. These results
      strongly suggest that DSB repair can be a major source of amplification of
      tandemly repeated sequences. Most of the DSB repair events are not associated
      with crossover. Rearrangements appear in 50% of these repaired recipient
      molecules. In contrast, the donor template nearly always remains unchanged. Among
      the rare crossover events, similar rearrangements are found. These results cannot
      readily be explained by the gap repair model of Szostak et al. (J. W. Szostak, T.
      L. Orr-Weaver, R. J. Rothstein, and F. W. Stahl, Cell 33:25-35, 1983) but can be
      explained by synthesis-dependent strand annealing (SDSA) models that allow for
      crossover. Support for SDSA models is provided by a demonstration that a single
      DSB repair event can use two donor templates located on two different
      chromosomes.

PMID- 9528778
TI  - Synthetic lethality of yeast slt mutations with U2 small nuclear RNA mutations
      suggests functional interactions between U2 and U5 snRNPs that are important for
      both steps of pre-mRNA splicing.
AB  - A genetic screen was devised to identify Saccharomyces cerevisiae splicing
      factors that are important for the function of the 5' end of U2 snRNA. Six slt
      (stands for synthetic lethality with U2) mutants were isolated on the basis of
      synthetic lethality with a U2 snRNA mutation that perturbs the U2-U6 snRNA helix
      II interaction. SLT11 encodes a new splicing factor and SLT22 encodes a new RNA
      dependent ATPase RNA helicase (D. Xu, S. Nouraini, D. Field, S. J. Tang, and J.
      D. Friesen, Nature 381:709-713, 1996). The remaining four slt mutations are new
      alleles of previously identified splicing genes: slt15, previously identified as
      prp17 (slt15/prp17-100), slt16/smd3-1, slt17/slu7-100, and slt21/prp8-21. slt11-1
      and slt22-1 are synthetically lethal with mutations in the 3' end of U6 snRNA, a
      region that affects U2-U6 snRNA helix II; however, slt17/slu7-100 and slt21/prp8
      21 are not. This difference suggests that the latter two factors are unlikely to
      be involved in interactions with U2-U6 snRNA helix II but rather are specific to
      interactions with U2 snRNA. Pairwise synthetic lethality was observed among slt11
      1 (which affects the first step of splicing) and several second-step factors,
      including slt15/prp17-100, slt17/slu7-100, and prp16-1. Mutations in loop 1 of U5
      snRNA, a region that is implicated in the alignment of the two exons, are
      synthetically lethal with slu4/prp17-2 and slu7-1 (D. Frank, B. Patterson, and C.
      Guthrie, Mol. Cell. Biol. 12:5179-5205, 1992), as well as with slt11-1,
      slt15/prp17-100, slt17/slu7-100, and slt21/prp8-21. These same U5 snRNA mutations
      also interact genetically with certain U2 snRNA mutations that lie in the helix I
      and helix II regions of the U2-U6 snRNA structure. Our results suggest
      interactions among U2 snRNA, U5 snRNA, and Slt protein factors that may be
      responsible for coupling and coordination of the two reactions of pre-mRNA
      splicing.

PMID- 9528779
TI  - Lens-specific gene recruitment of zeta-crystallin through Pax6, Nrl-Maf, and
      brain suppressor sites.
AB  - Zeta-Crystallin is a taxon-specific crystallin, an enzyme which has undergone
      direct gene recruitment as a structural component of the guinea pig lens through
      a Pax6-dependent mechanism. Tissue specificity arises through a combination of
      effects involving three sites in the lens promoter. The Pax6 site (ZPE) itself
      shows specificity for an isoform of Pax6 preferentially expressed in lens cells.
      High-level expression of the promoter requires a second site, identical to an
      alphaCE2 site or half Maf response element (MARE), adjacent to the Pax6 site. A
      promoter fragment containing Pax6 and MARE sites gives lens-preferred induction
      of a heterologous promoter. Complexes binding the MARE in lens nuclear extracts
      are antigenically related to Nrl, and cotransfection with Nrl elevates zeta
      crystallin promoter activity in lens cells. A truncated zeta promoter containing
      Nrl-MARE and Pax6 sites has a high level of expression in lens cells in
      transgenic mice but is also active in the brain. Suppression of the promoter in
      the brain requires sequences between -498 and -385, and a site in this region
      forms specific complexes in brain extract. A three-level model for lens-specific
      Pax6-dependent expression and gene recruitment is suggested: (i) binding of a
      specific isoform of Pax6; (ii) augmentation of expression through binding of Nrl
      or a related factor; and (iii) suppression of promoter activity in the central
      nervous system by an upstream negative element in the brain but not in the lens.

PMID- 9528780
TI  - NF-kappaB2 is a putative target gene of activated Notch-1 via RBP-Jkappa.
AB  - NF-kappaB2 (p100/p52), a member of the NF-kappaB/Rel family of transcription
      factors, is involved in the regulation of a variety of genes important for immune
      function. Previously, we have shown that the NF-kappaB2 gene is regulated in a
      positive and a negative manner. Two kappaB elements within the NF-kappaB2
      promoter mediate tumor necrosis factor alpha-inducible transactivation. In
      addition, we have shown that there exists a transcriptional repression in the
      absence of NF-kappaB. To identify a DNA binding activity responsible for this
      transcriptional repression, we have partially purified a nuclear complex, named
      Rep-kappaB. Here we further analyze this putative repressive binding activity.
      Detailed examination of Rep-kappaB-DNA interaction revealed the sequence
      requirements for binding to be almost identical to those of recombination signal
      binding protein Jkappa (RBP-Jkappa), the mammalian homolog of the protein encoded
      by Drosophila suppressor of hairless [Su(H)]. In addition, in electromobility
      shift assays, Rep-kappaB binding activity is recognized by an antibody directed
      against RBP-Jkappa. By performing transient-transfection assays, we show that
      human RBP-Jkappa represses basal as well as RelA (p65)-stimulated NF-kappaB2
      promoter activity. Studies in Drosophila melanogaster have shown that Su(H) is
      implicated in the Notch signaling pathway regulating cell fate decisions. In
      transient-transfection assays we show that truncated Notch-1 strongly induces NF
      kappaB2 promoter activity. In summary, our data clearly demonstrate that Rep
      kappaB is closely related or identical to RBP-Jkappa. RBP-Jkappa is a strong
      transcriptional repressor of NF-kappaB2. Moreover, this repression can be
      overcome by activated Notch-1, suggesting that NF-kappaB2 is a novel putative
      Notch target gene.

PMID- 9528781
TI  - SHP-1 binds and negatively modulates the c-Kit receptor by interaction with
      tyrosine 569 in the c-Kit juxtamembrane domain.
AB  - The SH2 domain-containing SHP-1 tyrosine phosphatase has been shown to negatively
      regulate a broad spectrum of growth factor- and cytokine-driven mitogenic
      signaling pathways. Included among these is the cascade of intracellular events
      evoked by stem cell factor binding to c-Kit, a tyrosine kinase receptor which
      associates with and is dephosphorylated by SHP-1. Using a series of glutathione S
      transferase (GST) fusion proteins containing either tyrosine-phosphorylated
      segments of the c-Kit cytosolic region or the SH2 domains of SHP-1, we have shown
      that SHP-1 interacts with c-Kit by binding selectively to the phosphorylated c
      Kit juxtamembrane region and that the association of c-Kit with the larger of the
      two SHP-1 isoforms may be mediated through either the N-terminal or C-terminal
      SHP-1 SH2 domain. The results of binding assays with mutagenized GST-Kit
      juxtamembrane fusion proteins and competitive inhibition assays with
      phosphopeptides encompassing each c-Kit juxtamembrane region identified the
      tyrosine residue at position 569 as the major site for binding of SHP-1 to c-Kit
      and suggested that tyrosine 567 contributes to, but is not required for, this
      interaction. By analysis of Ba/F3 cells retrovirally transduced to express c-Kit
      receptors, phenylalanine substitution of c-Kit tyrosine residue 569 was shown to
      be associated with disruption of c-Kit-SHP-1 binding and induction of
      hyperproliferative responses to stem cell factor. Although phenylalanine
      substitution of c-Kit tyrosine residue 567 in the Ba/F3-c-Kit cells did not alter
      SHP-1 binding to c-Kit, the capacity of a second c-Kit-binding tyrosine
      phosphatase, SHP-2, to associate with c-Kit was markedly reduced, and the cells
      again showed hyperproliferative responses to stem cell factor. These data
      therefore identify SHP-1 binding to tyrosine 569 on c-Kit as an interaction
      pivotal to SHP-1 inhibitory effects on c-Kit signaling, but they indicate as well
      that cytosolic protein tyrosine phosphatases other than SHP-1 may also negatively
      regulate the coupling of c-Kit engagement to proliferation.

PMID- 9528782
TI  - DBF2 protein kinase binds to and acts through the cell cycle-regulated MOB1
      protein.
AB  - The DBF2 gene of the budding yeast Saccharomyces cerevisiae encodes a cell cycle
      regulated protein kinase that plays an important role in the telophase/G1
      transition. As a component of the multisubunit CCR4 transcriptional complex, DBF2
      is also involved in the regulation of gene expression. We have found that MOB1,
      an essential protein required for a late mitotic event in the cell cycle,
      genetically and physically interacts with DBF2. DBF2 binds MOB1 in vivo and can
      bind it in vitro in the absence of other yeast proteins. We found that the
      expression of MOB1 is also cell cycle regulated, its expression peaking slightly
      before that of DBF2 at the G2/M boundary. While overexpression of DBF2 suppressed
      phenotypes associated with mob1 temperature-sensitive alleles, it could not
      suppress a mob1 deletion. In contrast, overexpression of MOB1 suppressed
      phenotypes associated with a dbf2-deleted strain and suppressed the lethality
      associated with a dbf2 dbf20 double deletion. A mob1 temperature-sensitive allele
      with a dbf2 disruption was also found to be synthetically lethal. These results
      are consistent with DBF2 acting through MOB1 and aiding in its function.
      Moreover, the ability of temperature-sensitive mutated versions of the MOB1
      protein to interact with DBF2 was severely reduced, confirming that binding of
      DBF2 to MOB1 is required for a late mitotic event. While MOB1 and DBF2 were found
      to be capable of physically associating in a complex that did not include CCR4,
      MOB1 did interact with other components of the CCR4 transcriptional complex. We
      discuss models concerning the role of DBF2 and MOB1 in controlling the
      telophase/G1 transition.

PMID- 9528783
TI  - Interleukin-6-specific activation of the C/EBPdelta gene in hepatocytes is
      mediated by Stat3 and Sp1.
AB  - C/EBPdelta (CCAAT/enhancer binding protein delta) has been implicated as a
      regulator of acute-phase response (APR) genes in hepatocytes. Its expression
      increases dramatically in liver during the APR and can be induced in hepatic cell
      lines by interleukin-6 (IL-6), an acute-phase mediator that activates
      transcription of many APR genes. Here we have investigated the mechanism by which
      C/EBPdelta expression is regulated by IL-6 in hepatoma cells. C/EBPdelta promoter
      sequences to -125 bp are sufficient for IL-6 inducibility of a reporter gene and
      include an APR element (APRE) that is essential for IL-6 responsiveness. DNA
      binding experiments and transactivation assays demonstrate that Stat3, but not
      Stat1, interacts with this APRE. Two Sp1 sites, one of which is adjacent to the
      APRE, are required for IL-6 induction and transactivation by Stat3. Thus, Stat3
      and Sp1 function cooperatively to activate the C/EBPdelta promoter. Replacement
      of the APRE with Stat binding elements (SBEs) from the ICAM-1 or C/EBPbeta
      promoter, both of which recognize both Stat1 and Stat3, confers responsiveness to
      gamma interferon, a cytokine that selectively activates Stat1. Sequence
      comparisons suggest that the distinct Stat binding specificities of the
      C/EBPdelta and C/EBPbeta SBEs are determined primarily by a single base pair
      difference. Our findings indicate that the cytokine specificity of C/EBPdelta
      gene expression is governed by the APRE sequence.

PMID- 9528784
TI  - The Schizosaccharomyces pombe mei4+ gene encodes a meiosis-specific transcription
      factor containing a forkhead DNA-binding domain.
AB  - The mei4+ gene of the fission yeast Schizosaccharomyces pombe was cloned by
      functional complementation. The mei4 disruptant failed to complete meiosis-I but
      could proliferate normally. mei4+ was transcribed only in meiosis-proficient
      diploid cells after premeiotic DNA replication. The mei4+ open reading frame
      encodes a 57-kDa serine-rich protein comprised of 517 amino acids with a
      forkhead/HNF3 DNA-binding domain in the amino-terminal region. Transcription of
      spo6+, a gene required for sporulation, was dependent on the mei4+ function. Two
      copies of the GTAAAYA consensus sequence, proposed as the binding site for human
      forkhead proteins, were found in the promoter region of spo6+. A gel mobility
      shift assay demonstrated the sequence-dependent binding of the GST-Mei4 forkhead
      domain fusion protein to DNA fragments with one of the consensus elements.
      Deletion of this consensus element from the spo6 promoter abolished the
      transcription of spo6+ and resulted in a sporulation deficiency. One-hybrid assay
      of Mei4 which was fused to the Gal4 DNA-binding domain localized the
      transcriptional activation domain in the C-terminal 140 amino acids of Mei4.
      These results indicate that Mei4 functions as a meiosis-specific transcription
      factor of S. pombe.

PMID- 9528785
TI  - Functions of the N- and C-terminal domains of human RAP74 in transcriptional
      initiation, elongation, and recycling of RNA polymerase II.
AB  - Transcription factor IIF (TFIIF) cooperates with RNA polymerase II (pol II)
      during multiple stages of the transcription cycle including preinitiation complex
      assembly, initiation, elongation, and possibly termination and recycling. Human
      TFIIF appears to be an alpha2beta2 heterotetramer of RNA polymerase II
      associating protein 74- and 30-kDa subunits (RAP74 and RAP30). From inspection of
      its 517-amino-acid (aa) sequence, the RAP74 subunit appears to comprise separate
      N- and C-terminal domains connected by a flexible loop. In this study, we present
      functional data that strongly support this model for RAP74 architecture and
      further show that the N- and C-terminal domains and the central loop of RAP74
      have distinct roles during separate phases of the transcription cycle. The N
      terminal domain of RAP74 (minimally aa 1 to 172) is sufficient to deliver pol II
      into a complex formed on the adenovirus major late promoter with the TATA-binding
      protein, TFIIB, and RAP30. A more complete N-terminal domain fragment (aa 1 to
      217) strongly stimulates both accurate initiation and elongation by pol II. The
      region of RAP74 between aa 172 and 205 and a subregion between aa 170 and 178 are
      critical for both accurate initiation and elongation, and mutations in these
      regions have similar effects on initiation and elongation. Based on these
      observations, RAP74 appears to have similar functions in initiation and
      elongation. The central region and the C-terminal domain of RAP74 do not
      contribute strongly to single-round accurate initiation or elongation stimulation
      but do stimulate multiple-round transcription in an extract system.

PMID- 9528786
TI  - Akt, a target of phosphatidylinositol 3-kinase, inhibits apoptosis in a
      differentiating neuronal cell line.
AB  - Phosphatidylinositol (PI) 3-kinase has been suggested to mediate cell survival.
      Consistent with this possibility, apoptosis of conditionally (simian virus 40
      Tts) immortalized rat hippocampal H19-7 neuronal cells was increased in response
      to wortmannin, an inhibitor of PI 3-kinase. Downstream effectors of PI 3-kinase
      include Rac1, protein kinase C, and the serine-threonine kinase Akt (protein
      kinase B). Here, we show that activation of Akt is one mechanism by which PI 3
      kinase can mediate survival of H19-7 cells during serum deprivation or
      differentiation. While ectopic expression of wild-type Akt (c-Akt) does not
      significantly enhance survival in H19-7 cells, expression of activated forms of
      Akt (v-Akt or myristoylated Akt) results in enhanced survival which can be
      comparable to that conferred by Bcl-2. Conversely, expression of a dominant
      negative mutant of Akt accelerates cell death upon serum deprivation or
      differentiation. Finally, the results indicate that Akt can transduce a survival
      signal for differentiating neuronal cells through a mechanism that is independent
      of induction of Bcl-2 or Bcl-XL or inhibition of Jun kinase activity.

PMID- 9528787
TI  - A conserved negative regulatory region in alphaPAK: inhibition of PAK kinases
      reveals their morphological roles downstream of Cdc42 and Rac1.
AB  - AlphaPAK in a constitutively active form can exert morphological effects (E.
      Manser, H.-Y. Huang, T.-H. Loo, X.-Q. Chen, J.-M. Dong, T. Leung, and L. Lim,
      Mol. Cell. Biol. 17:1129-1143, 1997) resembling those of Cdc42G12V. PAK family
      kinases, conserved from yeasts to humans, are directly activated by Cdc42 or Rac1
      through interaction with a conserved N-terminal motif (corresponding to residues
      71 to 137 in alphaPAK). alphaPAK mutants with substitutions in this motif that
      resulted in severely reduced Cdc42 binding can be recruited normally to Cdc42G12V
      driven focal complexes. Mutation of residues in the C-terminal portion of the
      motif (residues 101 to 137), though not affecting Cdc42 binding, produced a
      constitutively active kinase, suggesting this to be a negative regulatory region.
      Indeed, a 67-residue polypeptide encoding alphaPAK83-149 potently inhibited
      GTPgammaS-bound Cdc42-mediated kinase activation of both alphaPAK and betaPAK.
      Coexpression of this PAK inhibitor with Cdc42G12V prevented the formation of
      peripheral actin microspikes and associated loss of stress fibers normally
      induced by the p21. Coexpression of PAK inhibitor with Rac1G12V also prevented
      loss of stress fibers but not ruffling induced by the p21. Coexpression of
      alphaPAK83-149 completely blocked the phenotypic effects of hyperactive
      alphaPAKL107F in promoting dissolution of focal adhesions and actin stress
      fibers. These results, coupled with previous observations with constitutively
      active PAK, demonstrate that these kinases play an important role downstream of
      Cdc42 and Rac1 in cytoskeletal reorganization.

PMID- 9528788
TI  - Phosphorylation of the kinase homology domain is essential for activation of the
      A-type natriuretic peptide receptor.
AB  - Natriuretic peptide receptor A (NPR-A) is the biological receptor for atrial
      natriuretic peptide (ANP). Activation of the NPR-A guanylyl cyclase requires ANP
      binding to the extracellular domain and ATP binding to a putative site within its
      cytoplasmic region. The allosteric interaction of ATP with the intracellular
      kinase homology domain (KHD) is hypothesized to derepress the carboxyl-terminal
      guanylyl cyclase catalytic domain, resulting in the synthesis of the second
      messenger, cyclic GMP. Here, we show that phosphorylation of the KHD is essential
      for receptor activation. Using a combination of phosphopeptide mapping
      techniques, we have identified six residues within the ATP-binding domain (S497,
      T500, S502, S506, S510, and T513) which are phosphorylated when NPR-A is
      expressed in HEK 293 cells. Mutation of any one of these Ser or Thr residues to
      Ala caused reductions in the receptor phosphorylation state, the number and
      pattern of phosphopeptides observed in tryptic maps, and ANP-dependent guanylyl
      cyclase activity. The reductions were not explained by decreases in NPR-A protein
      levels, as indicated by immunoblot analysis and determinations of cyclase
      activity in the presence of detergent. Conversion of Ser-497 to Ala resulted in
      the most dramatic decrease in cyclase activity (approximately 20% of wild-type
      activity), but conversion to an acidic residue (Glu), which mimics the charge of
      the phosphoserine moiety, had no effect. Simultaneous mutation of five of the
      phosphorylation sites to Ala resulted in a dephosphorylated receptor which was
      unresponsive to hormone and had potent dominant negative inhibitory activity. We
      conclude that phosphorylation of the KHD is absolutely required for hormone
      dependent activation of NPR-A.

PMID- 9528789
TI  - Sequence divergence in the 3' untranslated regions of human zeta- and alpha
      globin mRNAs mediates a difference in their stabilities and contributes to
      efficient alpha-to-zeta gene development switching.
AB  - The developmental stage-specific expression of human globin proteins is
      characterized by a switch from the coexpression of zeta- and alpha-globin in the
      embryonic yolk sac to exclusive expression of alpha-globin during fetal and adult
      life. Recent studies with transgenic mice demonstrate that in addition to
      transcriptional control elements, full developmental silencing of the human zeta
      globin gene requires elements encoded within the transcribed region. In the
      current work, we establish that these latter elements operate
      posttranscriptionally by reducing the relative stability of zeta-globin mRNA.
      Using a transgenic mouse model system, we demonstrate that human zeta-globin mRNA
      is unstable in adult erythroid cells relative to the highly stable human alpha
      globin mRNA. A critical determinant of the difference between alpha- and zeta
      globin mRNA stability is mapped by in vivo expression studies to their respective
      3' untranslated regions (3'UTRs). In vitro messenger ribonucleoprotein (mRNP)
      assembly assays demonstrate that the alpha- and zeta-globin 3'UTRs assemble a
      previously described mRNP stability-determining complex, the alpha-complex, with
      distinctly different affinities. The diminished efficiency of alpha-complex
      assembly on the zeta 3'UTR results from a single C-->G nucleotide substitution in
      a crucial polypyrimidine tract contained by both the human alpha- and zeta-globin
      mRNA 3'UTRs. A potential pathway for accelerated zeta-globin mRNA decay is
      suggested by the observation that its 3'UTR encodes a shortened poly(A) tail.
      Based upon these data, we propose a model for zeta-globin gene silencing in fetal
      and adult erythroid cells in which posttranscriptional controls play a central
      role by providing for accelerated clearance of zeta-globin transcripts.

PMID- 9528790
TI  - Characterization of BCE-1, a transcriptional enhancer regulated by prolactin and
      extracellular matrix and modulated by the state of histone acetylation.
AB  - We have previously described a 160-bp enhancer (BCE-1) in the bovine beta-casein
      gene that is activated in the presence of prolactin and extracellular matrix
      (ECM). Here we report the characterization of the enhancer by deletion and site
      directed mutagenesis, electrophoretic mobility shift analysis, and in vivo
      footprinting. Two essential regions were identified by analysis of mutant
      constructions: one binds C/EBP-beta and the other binds MGF/STAT5 and an as-yet
      unidentified binding protein. However, no qualitative or quantitative differences
      in the binding of these proteins were observed in electrophoretic mobility shift
      analysis using nuclear extracts derived from cells cultured in the presence or
      absence of ECM with or without prolactin, indicating that prolactin- and ECM
      induced transcription was not dependent on the availability of these factors in
      the functional cell lines employed. An in vivo footprinting analysis of the
      factors bound to nuclear chromatin in the presence or absence of ECM and/or
      prolactin found no differences in the binding of C/EBP-beta but did not provide
      definitive results for the other factors. Neither ECM nor prolactin activated BCE
      1 in transient transfections, suggesting that the chromosomal structure of the
      integrated template may be required for ECM-induced transcription. Further
      evidence is that treatment of cells with inhibitors of histone deacetylase was
      sufficient to induce transcription of integrated BCE-1 in the absence of ECM.
      Together, these results suggest that the ECM induces a complex interaction
      between the enhancer-bound transcription factors, the basal transcriptional
      machinery, and a chromosomally integrated template responsive to the acetylation
      state of the histones.

PMID- 9528791
TI  - Snt309p, a component of the Prp19p-associated complex that interacts with Prp19p
      and associates with the spliceosome simultaneously with or immediately after
      dissociation of U4 in the same manner as Prp19p.
AB  - The yeast protein Prp19p is essential for pre-mRNA splicing and is associated
      with the spliceosome concurrently with or just after dissociation of U4 small
      nuclear RNA. In splicing extracts, Prp19p is associated with several other
      proteins in a large protein complex of unknown function, but at least one of
      these proteins is also essential for splicing (W.-Y. Tarn, C.-H. Hsu, K.-T.
      Huang, H.-R. Chen, H.-Y. Kao, K.-R. Lee, and S.-C. Cheng, EMBO J. 13:2421-2431,
      1994). To identify proteins in the Prp19p-associated complex, we have isolated
      trans-acting mutations that exacerbate the phenotypes of conditional alleles of
      prp19, using the ade2-ade3 sectoring system. A novel splicing factor, Snt309p,
      was identified through such a screen. Although the SNT309 gene was not essential
      for growth of Saccharomyces cerevisiae under normal conditions, yeast cells
      containing a null allele of the SNT309 gene were temperature sensitive and
      accumulated pre-mRNA at the nonpermissive temperature. Far-Western blot analysis
      revealed direct interaction between Prp19p and Snt309p. Snt309p was shown to be a
      component of the Prp19p-associated complex by Western blot analysis.
      Immunoprecipitation studies demonstrated that Snt309p was also a spliceosomal
      component and associated with the spliceosome in the same manner as Prp19p during
      spliceosome assembly. These results suggest that the functions of Prp19p and
      Snt309p in splicing may require coordinate action of these two proteins.

PMID- 9528792
TI  - An intronic sequence element mediates both activation and repression of rat
      fibroblast growth factor receptor 2 pre-mRNA splicing.
AB  - Alternative splicing of fibroblast growth factor receptor 2 (FGF-R2) is an
      example of highly regulated alternative splicing in which exons IIIb and IIIc are
      utilized in a mutually exclusive manner in different cell types. The importance
      of this splicing choice is highlighted by studies which indicate that
      deregulation of the FGF-R2 splicing is associated with progression of prostate
      cancer. Loss of expression of a IIIb exon-containing isoform of FGF-R2 [FGF-R2
      (IIIb)] accompanies the transition of a well-differentiated, androgen-dependent
      rat prostate cancer cell line, DT3, to the more aggressive, androgen-independent
      AT3 cell line. We have used transfection of rat FGF-R2 minigenes into DT3 and AT3
      cancer cell lines to study the mechanisms that control alternative splicing of
      rat FGF-R2. Our results support a model in which an important cis-acting element
      located in the intron between these alternative exons mediates activation of
      splicing using the upstream IIIb exon and repression of the downstream IIIc exon
      in DT3 cells. This element consists of 57 nucleotides (nt) beginning 917 nt
      downstream of the IIIb exon. Analysis of mutants further demonstrates that an 18
      nt "core sequence" within this element is most crucial for its function. Based on
      our observations, we have termed this sequence element ISAR (for intronic
      splicing activator and repressor), and we suggest that factors which bind this
      sequence are required for maintenance of expression of the FGF-R2 (IIIb) isoform.

PMID- 9528793
TI  - A role for CREB binding protein and p300 transcriptional coactivators in Ets-1
      transactivation functions.
AB  - The Ets-1 transcription factor plays a critical role in cell growth and
      development, but the means by which it activates transcription are still unclear
      (J. C. Bories, D. M. Willerford, D. Grevin, L. Davidson, A. Camus, P. Martin, D.
      Stehelin, F. W. Alt, and J. C. Borles, Nature 377:635-638, 1995; N. Muthusamy, K.
      Barton, and J. M. Leiden, Nature 377:639-642, 1995). Here we show that Ets-1
      binds the transcriptional coactivators CREB binding protein (CBP) and the related
      p300 protein (together referred to as CBP/p300) and that this interaction is
      required for specific Ets-1 transactivation functions. The Ets-1- and c-Myb
      dependent aminopeptidase N (CD13/APN) promoter and an Ets-1-dependent artificial
      promoter were repressed by adenovirus E1A, a CBP/p300-specific inhibitor.
      Furthermore, Ets-1 activity was potentiated by CBP and p300 overexpression. The
      transactivation function of Ets-1 correlated with its ability to bind an N
      terminal cysteine- and histidine-rich region spanning CBP residues 313 to 452.
      Ets-1 also bound a second cysteine- and histidine-rich region of CBP, between
      residues 1449 and 1892. Both Ets-1 and CBP/p300 formed a stable
      immunoprecipitable nuclear complex, independent of DNA binding. This Ets-1
      CBP/p300 immunocomplex possessed histone acetyltransferase activity, consistent
      with previous findings that CBP/p300 is associated with such enzyme activity. Our
      results indicate that CBP/p300 may mediate antagonistic and synergistic
      interactions between Ets-1 and other transcription factors that use CBP/p300 as a
      coactivator, including c-Myb and AP-1.

PMID- 9528794
TI  - Notch inhibition of E47 supports the existence of a novel signaling pathway.
AB  - E47 is a widely expressed transcription factor that activates B-cell-specific
      immunoglobulin gene transcription and is required for early B-cell development.
      In an effort to identify processes that regulate E47, and potentially B-cell
      development, we found that activated Notch1 and Notch2 effectively inhibit E47
      activity. Only the intact E47 protein was inhibited by Notch-fusion proteins
      containing isolated DNA binding and activation domains were unaffected-suggesting
      that Notch targets an atypical E47 cofactor. Although overexpression of the
      coactivator p300 partially reversed E47 inhibition, results of several assays
      indicated that p300/CBP is not a general target of Notch. Notch inhibition of E47
      did not correlate with its ability to activate CBF1/RBP-Jkappa, the mammalian
      homolog of Suppressor of Hairless, a protein that associates physically with
      Notch and defines the only known Notch signaling pathway in drosophila.
      Importantly, E47 was inhibited independently of CBF1/RPB-Jkappa by Deltex, a
      second Notch-interacting protein. We provide evidence that Notch and Deltex may
      act on E47 by inhibiting signaling through Ras because (i) full E47 activity was
      found to be dependent on Ras and (ii) both Notch and Deltex inhibited GAL4-Jun, a
      hybrid transcription factor whose activity is dependent on signaling from Ras to
      SAPK/JNK.

PMID- 9528795
TI  - The tomato Hsf system: HsfA2 needs interaction with HsfA1 for efficient nuclear
      import and may be localized in cytoplasmic heat stress granules.
AB  - In heat-stressed (HS) tomato (Lycopersicon peruvianum) cell cultures, the
      constitutively expressed HS transcription factor HsfA1 is complemented by two HS
      inducible forms, HsfA2 and HsfB1. Because of its stability, HsfA2 accumulates to
      fairly high levels in the course of a prolonged HS and recovery regimen. Using
      immunofluorescence and cell fractionation experiments, we identified three states
      of HsfA2: (i) a soluble, cytoplasmic form in preinduced cultures maintained at 25
      degrees C, (ii) a salt-resistant, nuclear form found in HS cells, and (iii) a
      stored form of HsfA2 in cytoplasmic HS granules. The efficient nuclear transport
      of HsfA2 evidently requires interaction with HsfA1. When expressed in tobacco
      protoplasts by use of a transient-expression system, HsfA2 is mainly retained in
      the cytoplasm unless it is coexpressed with HsfA1. The essential parts for the
      interaction and nuclear cotransport of the two Hsfs are the homologous
      oligomerization domain (HR-A/B region of the A-type Hsfs) and functional nuclear
      localization signal motifs of both partners. Direct physical interaction of the
      two Hsfs with formation of relatively stabile hetero-oligomers was shown by a two
      hybrid test in Saccharomyces cerevisiae as well as by coimmunoprecipitation using
      tomato and tobacco whole-cell lysates.

PMID- 9528796
TI  - Adf-1 is a nonmodular transcription factor that contains a TAF-binding Myb-like
      motif.
AB  - Adf-1 is an essential Drosophila melanogaster sequence-specific transactivator
      that binds the promoters of a diverse group of genes. We have performed a
      comprehensive mapping of the functional domains of Adf-1 to study the role of
      transactivators in the process of gene activation. Using a series of clustered
      point mutations and small deletions we have identified regions of Adf-1 required
      for DNA binding, dimerization, and activation. In contrast to most enhancer
      binding factors, the Adf-1 activation regions are nonmodular and depend on an
      intact protein, including the Adf-1 DNA-binding domain, for activity. Like many
      transcriptional activators, Adf-1 contains a TFIID-binding domain that can
      interact with specific TAF subunits. Although TAFs are required for Adf-1
      directed activation, TAF binding is not sufficient, suggesting that Adf-1 may
      direct multiple essential steps during activation. Interestingly, both the TAF
      binding domain and the DNA-binding domain contain sequences homologous to those
      of the Myb family of DNA-binding domains. Thus, Adf-1 has evolved an unusual
      structure containing two versions of the Myb motif, one that binds DNA and one
      that binds proteins.

PMID- 9528797
TI  - The microsatellite sequence (CT)n x (GA)n promotes stable chromosomal integration
      of large tandem arrays of functional human U2 small nuclear RNA genes.
AB  - The multigene family encoding human U2 small nuclear RNA (snRNA) is organized as
      a single large tandem array containing 5 to 25 copies of a 6.1-kb repeat unit
      (the RNU2 locus). Remarkably, each of the repeat units within an individual U2
      tandem array appears to be identical except for an irregular dinucleotide tract,
      known as the CT microsatellite, which exhibits minor length and sequence
      polymorphism. Using a somatic cell genetic assay, we previously noticed that the
      CT microsatellite appeared to stabilize artificial tandem arrays of U2 snRNA
      genes. We now demonstrate that the CT microsatellite is required to establish
      large tandem arrays of transcriptionally active U2 genes, increasing both the
      average and maximum size of the resulting arrays. In contrast, the CT
      microsatellite has no effect on the average or maximal size of artificial arrays
      containing transcriptionally inactive U2 genes that lack key promoter elements.
      Our data reinforce the connection between recombination and transcription. Active
      U2 transcription interferes with establishment or maintenance of the U2 tandem
      array, and the CT microsatellite opposes these effects, perhaps by binding GAGA
      or GAGA-related factors which alter local chromatin structure. We speculate that
      the mechanisms responsible for maintenance of tandem arrays containing active
      promoters may differ from those that maintain tandem arrays of transcriptionally
      inactive sequences.

PMID- 9528798
TI  - Raf and fibroblast growth factor phosphorylate Elk1 and activate the serum
      response element of the immediate early gene pip92 by mitogen-activated protein
      kinase-independent as well as -dependent signaling pathways.
AB  - Previous studies have shown that a mitogen activated protein (MAP) kinase (MEK)
      independent signaling pathway is required by activated Raf or fibroblast-derived
      growth factor (FGF) for the differentiation of rat hippocampal neuronal H19-7
      cells. We now demonstrate that both Raf and FGF similarly induce prolonged
      transcription and translation of the immediate early gene pip92 in the absence of
      activation of the MAP kinases (MAPKs) ERK1 and ERK2. To determine the mechanism
      by which this occurs and to identify novel Raf-activated signaling pathways, we
      investigated the induction of the pip92 promoter by both FGF and an estradiol
      activated Raf-1-estrogen receptor fusion protein (deltaRaf-1:ER) in H19-7 cells.
      Deletion analysis of the pip92 promoter indicated that activation by the MAPK
      independent pathway occurs primarily within the region containing a serum
      response element (SRE). Further analysis of the SRE by using a heterologous
      thymidine kinase promoter showed that both an Ets and CArG-like site are
      required. Elk1, which binds to the Ets site, was phosphorylated both in vitro and
      in vivo by the MAPK-independent pathway, and phosphorylation of an Elk1-GAL4
      fusion protein by this pathway was sufficient for transactivation. Finally, at
      least two Elk1 kinases were fractionated by gel filtration, and analysis by an in
      gel kinase assay revealed at least three novel Raf-activated Elk1 kinases. These
      results indicate that both FGF and Raf activate MAPK-independent kinases that can
      stimulate Elk1 phosphorylation and immediate early gene transcription.

PMID- 9528799
TI  - Autophosphorylation in the activation loop is required for full kinase activity
      in vivo of human and yeast eukaryotic initiation factor 2alpha kinases PKR and
      GCN2.
AB  - The human double-stranded RNA-dependent protein kinase (PKR) is an important
      component of the interferon response to virus infection. The activation of PKR is
      accompanied by autophosphorylation at multiple sites, including one in the N
      terminal regulatory region (Thr-258) that is required for full kinase activity.
      Several protein kinases are activated by phosphorylation in the region between
      kinase subdomains VII and VIII, referred to as the activation loop. We show that
      Thr-446 and Thr-451 in the PKR activation loop are required in vivo and in vitro
      for high-level kinase activity. Mutation of either residue to Ala impaired
      translational control by PKR in yeast cells and COS1 cells and led to tumor
      formation in mice. These mutations also impaired autophosphorylation and
      eukaryotic initiation factor 2 subunit alpha (eIF2alpha) phosphorylation by PKR
      in vitro. Whereas the Ala-446 substitution substantially reduced PKR function,
      the mutant kinase containing Ala-451 was completely inactive. PKR specifically
      phosphorylated Thr-446 and Thr-451 in synthetic peptides in vitro, and mass
      spectrometry analysis of PKR phosphopeptides confirmed that Thr-446 is an
      autophosphorylation site in vivo. Substitution of Glu-490 in subdomain X of PKR
      partially restored kinase activity when combined with the Ala-451 mutation. This
      finding suggests that the interaction between subdomain X and the activation
      loop, described previously for MAP kinase, is a regulatory feature conserved in
      PKR. We found that the yeast eIF2alpha kinase GCN2 autophosphorylates at Thr-882
      and Thr-887, located in the activation loop at exactly the same positions as Thr
      446 and Thr-451 in PKR. Thr-887 was more critically required than was Thr-882 for
      GCN2 kinase activity, paralleling the relative importance of Thr-446 and Thr-451
      in PKR. These results indicate striking similarities between GCN2 and PKR in the
      importance of autophosphorylation and the conserved Thr residues in the
      activation loop.

PMID- 9528802
TI  - Notch1 and Notch2 inhibit myeloid differentiation in response to different
      cytokines.
AB  - We have compared the ability of two mammalian Notch homologs, mouse Notchl and
      Notch2, to inhibit the granulocytic differentiation of 32D myeloid progenitor
      cells. 32D cells undergo granulocytic differentiation when stimulated with either
      granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony
      stimulating factor (GM-CSF). Expression of the activated intracellular domain of
      Notch1 inhibits the differentiation induced by G-CSF but not by GM-CSF;
      conversely, the corresponding domain of Notch2 inhibits differentiation in
      response to GM-CSF but not to G-CSF. The region immediately C-terminal to the
      cdc10 domain of Notch confers cytokine specificity on the cdc10 domain. The
      cytokine response patterns of Notch1 and Notch2 are transferred with this region,
      which we have termed the Notch cytokine response (NCR) region. The NCR region is
      also associated with differences in posttranslational modification and
      subcellular localization of the different Notch molecules. These findings suggest
      that the multiple forms of Notch found in mammals have structural differences
      that allow their function to be modulated by specific differentiation signals.

PMID- 9528801
TI  - Ca2+ content and expression of an acidocalcisomal calcium pump are elevated in
      intracellular forms of Trypanosoma cruzi.
AB  - The survival of a eukaryotic protozoan as an obligate parasite in the interior of
      a eukaryotic host cell implies its adaptation to an environment with a very
      different ionic composition from that of its extracellular habitat. This is
      particularly important in the case of Ca2+, the intracellular concentration of
      which is 3 orders of magnitude lower than the extracellular value. Ca2+ entry
      across the plasma membrane is a widely recognized mechanism for Ca2+ signaling,
      needed for a number of intracellular processes, and obviously, it would be
      restricted in the case of intracellular parasites. Here we show that Trypanosoma
      cruzi amastigotes possess a higher Ca2+ content than the extracellular stages of
      the parasite. This correlates with the higher expression of a calcium pump, the
      gene for which was cloned and sequenced. The deduced protein product (Tca1) of
      this gene has a calculated molecular mass of 121,141 Da and exhibits 34 to 38%
      identity with vacuolar Ca2+-ATPases of Saccharomyces cerevisiae and Dictyostelium
      discoideum, respectively. The tca1 gene suppresses the Ca2+ hypersensitivity of a
      mutant of S. cerevisiae that has a defect in vacuolar Ca2+ accumulation. Indirect
      immunofluorescence and immunoelectron microscopy analysis indicate that Tca1
      colocalizes with the vacuolar H+-ATPase to the plasma membrane and to
      intracellular vacuoles of T. cruzi. These vacuoles were shown to have the same
      size and distribution as the calcium-containing vacuoles identified by the
      potassium pyroantimoniate-osmium technique and as the electron-dense vacuoles
      observed in whole unfixed parasites by transmission electron microscopy and
      identified in a previous work (D. A. Scott, R. Docampo, J. A. Dvorak, S. Shi, and
      R. D. Leapman, J. Biol. Chem. 272:28020-28029, 1997) as being acidic and
      possessing a high calcium content (i.e., acidocalcisomes). Together, these
      results suggest that acidocalcisomes are distinct from other previously
      recognized organelles present in these parasites and underscore the ability of
      intracellular parasites to adapt to the hostile environment of their hosts.

PMID- 9528803
TI  - Coupled transcriptional and translational control of cyclin-dependent kinase
      inhibitor p18INK4c expression during myogenesis.
AB  - Terminal differentiation of many cell types involves permanent withdrawal from
      the cell division cycle. The p18INK4c protein, a member of the p16/INK4 cyclin
      dependent kinase (CDK) inhibitor family, is induced more than 50-fold during
      myogenic differentiation of mouse C2C12 myoblasts to become the predominant CDK
      inhibitor complexed with CDK4 and CDK6 in terminally differentiated myotubes. We
      have found that the p18INK4c gene expresses two mRNA transcripts--a 2.4-kb
      transcript, p18(L), and a 1.2-kb transcript, p18(S). In proliferating C2C12
      myoblasts, only the larger p18(L) transcript is expressed from an upstream
      promoter. As C2C12 cells are induced to differentiate into permanently arrested
      myotubes, the abundance of the p18(L) transcript decreases. The smaller p18(S)
      transcript expressed from a downstream promoter becomes detectable by 12 h
      postinduction and is the predominant transcript expressed in terminally
      differentiated myotubes. Both transcripts contain coding exons 2 and 3, but
      p18(L) uniquely contains an additional noncoding 1.2-kb exon, exon 1,
      corresponding exclusively to the 5' untranslated region (5' UTR). The expression
      pattern of the shorter p18(S) transcript, but not that of the longer p18(L)
      transcript, correlates with terminal differentiation of muscle, lung, liver,
      thymus, and eye lens cells during mouse embryo development. The presence of the
      long 5' UTR in exon 1 attenuated the translation of p18(L) transcript, while its
      absence from the shorter p18(S) transcript resulted in significantly more
      efficient translation of the p18 protein. Our results demonstrate that during
      terminal muscle cell differentiation, induction of the p18 protein is regulated
      by promoter switching coupled with translational control.

PMID- 9528800
TI  - Shc and Enigma are both required for mitogenic signaling by Ret/ptc2.
AB  - Ret/ptc2 is a constitutively active, oncogenic form of the c-Ret receptor
      tyrosine kinase. Like the other papillary thyroid carcinoma forms of Ret,
      Ret/ptc2 is activated through fusion of the Ret tyrosine kinase domain to the
      dimerization domain of another protein. Investigation of requirements for
      Ret/ptc2 mitogenic activity, using coexpression with dominant negative forms of
      Ras and Raf, indicated that these proteins are required for mitogenic signaling
      by Ret/ptc2. Because activation of Ras requires recruitment of Grb2 and SOS to
      the plasma membrane, the subcellular distribution of Ret/ptc2 was investigated,
      and it was found to localize to the cell periphery. This localization was
      mediated by association with Enigma via the Ret/ptc2 sequence containing tyrosine
      586. Because Shc interacts with MEN2 forms of Ret, and because phosphorylation of
      Shc results in Grb2 recruitment and subsequent signaling through Ras and Raf, the
      potential interaction between Ret/ptc2 and Shc was investigated. The PTB domain
      of Shc also interacted with Ret/ptc2 at tyrosine 586, and this association
      resulted in tyrosine phosphorylation of Shc. Coexpression of chimeric proteins
      demonstrated that mitogenic signaling from Ret/ptc2 required both recruitment of
      Shc and subcellular localization by Enigma. Because Shc and Enigma interact with
      the same site on a Ret/ptc2 monomer, dimerization of Ret/ptc2 allows assembly of
      molecular complexes that are properly localized via Enigma and transmit mitogenic
      signals via Shc.

PMID- 9528804
TI  - Requirement for both Shc and phosphatidylinositol 3' kinase signaling pathways in
      polyomavirus middle T-mediated mammary tumorigenesis.
AB  - Transgenic mice expressing the polyomavirus (PyV) middle T antigen (MT) develop
      multifocal mammary tumors which frequently metastasize to the lung. The potent
      transforming activity of PyV MT is correlated with its capacity to activate and
      associate with a number of signaling molecules, including the Src family tyrosine
      kinases, the 85-kDa Src homology 2 subunit of the phosphatidylinositol 3' (PI-3')
      kinase, and the Shc adapter protein. To uncover the role of these signaling
      proteins in MT-mediated mammary tumorigenesis, we have generated transgenic mice
      that express mutant PyV MT antigens decoupled from either the Shc or the PI-3'
      kinase signaling pathway. In contrast to the rapid induction of metastatic
      mammary tumors observed in the strains expressing wild-type PyV MT, mammary
      epithelial cell-specific expression of either mutant PyV MT resulted in the
      induction of extensive mammary epithelial hyperplasias. The mammary epithelial
      hyperplasias expressing the mutant PyV MT defective in recruiting the PI-3'
      kinase were highly apoptotic, suggesting that recruitment of PI-3' kinase by MT
      affects cell survival. Whereas the initial phenotypes observed in both strains
      were global mammary epithelial hyperplasias, focal mammary tumors eventually
      arose in all female transgenic mice. Genetic and biochemical analyses of
      tumorigenesis in the transgenic strains expressing the PyV MT mutant lacking the
      Shc binding site revealed that a proportion of the metastatic tumors arising in
      these mice displayed evidence of reversion of the mutant Shc binding site. In
      contrast, no evidence of reversion of the PI-3' kinase binding site was noted in
      tumors derived from the strains expressing the PI-3' kinase binding site MT
      mutant. Tumor progression in both mutant strains was further correlated with
      upregulation of the epidermal growth factor receptor family members which are
      known to couple to the PI-3' kinase and Shc signaling pathways. Taken together,
      these observations suggest that PyV MT-mediated tumorigenesis requires activation
      of both Shc and PI-3' kinase, which appear to be required for stimulation of cell
      proliferation and survival signaling pathways, respectively.

PMID- 9528805
TI  - Yeast 18S rRNA dimethylase Dim1p: a quality control mechanism in ribosome
      synthesis?
AB  - One of the few rRNA modifications conserved between bacteria and eukaryotes is
      the base dimethylation present at the 3' end of the small subunit rRNA. In the
      yeast Saccharomyces cerevisiae, this modification is carried out by Dim1p. We
      previously reported that genetic depletion of Dim1p not only blocked this
      modification but also strongly inhibited the pre-rRNA processing steps that lead
      to the synthesis of 18S rRNA. This prevented the formation of mature but
      unmodified 18S rRNA. The processing steps inhibited were nucleolar, and
      consistent with this, Dim1p was shown to localize mostly to this cellular
      compartment. dim1-2 was isolated from a library of conditionally lethal alleles
      of DIM1. In dim1-2 strains, pre-rRNA processing was not affected at the
      permissive temperature for growth, but dimethylation was blocked, leading to
      strong accumulation of nondimethylated 18S rRNA. This demonstrates that the
      enzymatic function of Dim1p in dimethylation can be separated from its
      involvement in pre-rRNA processing. The growth rate of dim1-2 strains was not
      affected, showing the dimethylation to be dispensable in vivo. Extracts of dim1-2
      strains, however, were incompetent for translation in vitro. This suggests that
      dimethylation is required under the suboptimal in vitro conditions but only fine
      tunes ribosomal function in vivo. Unexpectedly, when transcription of pre-rRNA
      was driven by a polymerase II PGK promoter, its processing became insensitive to
      temperature-sensitive mutations in DIM1 or to depletion of Dim1p. This
      observation, which demonstrates that Dim1p is not directly required for pre-rRNA
      processing reactions, is consistent with the inhibition of pre-rRNA processing by
      an active repression system in the absence of Dim1p.

PMID- 9528806
TI  - Coupling of cell growth control and apoptosis functions of Id proteins.
AB  - The Id family of helix-loop-helix proteins function as negative regulators of
      cell differentiation and as positive regulators of G1 cell cycle control. We
      report here that enforced overexpression of the Id3 gene suppresses the colony
      forming efficiency of primary rat embryo fibroblasts. Cotransfection with the
      antiapoptotic Bcl2 or BclXL gene alleviates this suppression and leads to cell
      immortalization. Consistent with this, enforced expression of Id genes in
      isolation was found to be a strong inducer of apoptosis in serum-deprived
      fibroblast cells. Id3-induced apoptosis was mediated at least in part through p53
      independent mechanisms and could be efficiently rescued by Bcl2, BclXL, and the
      basic helix-loop-helix protein E47, which is known to oppose the functions of Id3
      in vivo through the formation of stable heterodimers. Enforced overexpression of
      Id proteins has previously been shown to promote the cell cycle S phase in serum
      deprived embryo fibroblasts (R. W. Deed, E. Hara, G. Atherton, G. Peters, and J.
      D. Norton, Mol. Cell. Biol. 17:6815-6821, 1997). The extent of apoptosis induced
      by loss- and gain-of-function Id3 mutants and by wild-type Id3 either alone or in
      combination with the Bcl2, BClXL, and E47 genes was invariably correlated with
      the relative magnitude of cell cycle S phase promotion. In addition, Id3
      transfected cell populations displaying apoptosis and those in S phase were
      largely coincident in different experiments. These findings highlight the close
      coupling between the G1 progression and apoptosis functions of Id proteins and
      hint at a common mechanism for this family of transcriptional regulators in cell
      determination.

PMID- 9528807
TI  - Human matrix attachment regions insulate transgene expression from chromosomal
      position effects in Drosophila melanogaster.
AB  - Germ line transformation of white- Drosophila embryos with P-element vectors
      containing white expression cassettes results in flies with different eye color
      phenotypes due to position effects at the sites of transgene insertion. These
      position effects can be cured by specific DNA elements, such as the Drosophila
      scs and scs' elements, that have insulator activity in vivo. We have used this
      system to determine whether human matrix attachment regions (MARs) can function
      as insulator elements in vivo. Two different human MARs, from the apolipoprotein
      B and alpha1-antitrypsin loci, insulated white transgene expression from position
      effects in Drosophila melanogaster. Both elements reduced variability in
      transgene expression without enhancing levels of white gene expression. In
      contrast, expression of white transgenes containing human DNA segments without
      matrix-binding activity was highly variable in Drosophila transformants. These
      data indicate that human MARs can function as insulator elements in vivo.

PMID- 9528808
TI  - Differential transcriptional activation by human T-cell leukemia virus type 1 Tax
      mutants is mediated by distinct interactions with CREB binding protein and p300.
AB  - The human T-cell leukemia virus type 1 Tax protein transforms human T
      lymphocytes, which can lead to the development of adult T-cell leukemia. Tax
      transformation is related to its ability to activate gene expression via the
      ATF/CREB and the NF-kappaB pathways. Transcriptional activation of these pathways
      is mediated by the actions of the related coactivators CREB binding protein (CBP)
      and p300. In this study, immunocytochemistry and confocal microscopy were used to
      localize CBP and p300 in cells expressing wild-type Tax or Tax mutants that are
      able to selectively activate gene expression from either the NF-kappaB or
      ATF/CREB pathway. Wild-type Tax colocalized with both CBP and p300 in nuclear
      bodies which also contained ATF-1 and the RelA subunit of NF-kappaB. However, a
      Tax mutant that selectively activates gene expression from only the ATF/CREB
      pathway colocalized with CBP but not p300, while a Tax mutant that selectively
      activates gene expression from only the NF-kappaB pathway colocalized with p300
      but not CBP. In vitro and in vivo protein interaction studies indicated that the
      integrity of two independent domains of Tax delineated by these mutants was
      involved in the direct interaction of Tax with either CBP or p300. These studies
      are consistent with a model in which activation of either the NF-kappaB or the
      ATF/CREB pathway by specific Tax mutants is mediated by distinct interactions
      with related coactivator proteins.

PMID- 9528809
TI  - A nuclear matrix protein interacts with the phosphorylated C-terminal domain of
      RNA polymerase II.
AB  - Yeast two-hybrid screening has led to the identification of a family of proteins
      that interact with the repetitive C-terminal repeat domain (CTD) of RNA
      polymerase II (A. Yuryev et al., Proc. Natl. Acad. Sci. USA 93:6975-6980, 1996).
      In addition to serine/arginine-rich SR motifs, the SCAFs (SR-like CTD-associated
      factors) contain discrete CTD-interacting domains. In this paper, we show that
      the CTD-interacting domain of SCAF8 specifically binds CTD molecules
      phosphorylated on serines 2 and 5 of the consensus sequence
      Tyr1Ser2Pro3Thr4Ser5Pro6Ser7. In addition, we demonstrate that SCAF8 associates
      with hyperphosphorylated but not with hypophosphorylated RNA polymerase II in
      vitro and in vivo. This result suggests that SCAF8 is not present in
      preinitiation complexes but rather associates with elongating RNA polymerase II.
      Immunolocalization studies show that SCAF8 is present in granular nuclear foci
      which correspond to sites of active transcription. We also provide evidence that
      SCAF8 foci are associated with the nuclear matrix. A fraction of these sites
      overlap with a subset of larger nuclear speckles containing phosphorylated
      polymerase II. Taken together, our results indicate a possible role for SCAF8 in
      linking transcription and pre-mRNA processing.

PMID- 9528811
TI  - Association of a disease approximating cholera caused by Vibrio cholerae of
      serogroups other than O1 and O139.
AB  - One hundred and six patients suffering from severe dehydrating diarrhoea were
      studied of whom 36 patients were positive for Vibrio cholerae. Out of 36, 15 were
      positive for V. cholerae O1, 10 for V. cholerae O139 and 11 for V. cholerae non
      O1 non-O139. O1 and O139 were positive for the 301-bp ctxA amplicon and 471-bp
      tcpA amplicon indicating that the strains possessed toxigenic capability whereas
      no non-O1 non-O139 strain possessed ctxA or tcpA genes. Post-admission severity
      of purging and amount of ORS required were less in the V. cholerae non-O1 non
      O139 group (P < 0.05) compared to the V. cholerae O1 and O139 groups. It appears
      from this study that a cholera-like clinical condition can be caused in the
      absence of CT as exemplified by strains of non-O1 non-O139.

PMID- 9528812
TI  - Funerals during the 1994 cholera epidemic in Guinea-Bissau, West Africa: the need
      for disinfection of bodies of persons dying of cholera.
AB  - The 1994 cholera epidemic in Guinea-Bissau resulted in 15,878 reported cases and
      306 deaths. Early in the epidemic, although the health ministry mandated that the
      bodies of persons dying of cholera be disinfected, outbreaks occurred in several
      villages following funerals in the region of Biombo. To determine the influence
      of disinfection and funeral activities on cholera transmission, we analysed
      surveillance data and conducted a case-control study following a funeral. The
      attack rate during the week following funerals was higher in villages where
      bodies were not disinfected (risk ratio = 2.6, 95% confidence interval [CI] 1.9
      3.8). Cholera was strongly associated with eating at a funeral with a non
      disinfected corpse (odds ratio [OR] = 14.5, 95% CI 0.9-786) and with touching
      (i.e., transporting, washing) the body (OR = 36.2, 95% CI 2.6-1769). During
      cholera epidemics, in addition to other cholera prevention activities, health
      officials should inform community leaders about the risk of cholera transmission
      during funerals, meals should not be served at funerals, and bodies of persons
      dying of cholera should be disinfected.

PMID- 9528813
TI  - Escherichia coli O157:H7 diarrhoea associated with well water and infected cattle
      on an Ontario farm.
AB  - A 16-month old female child living on an Ontario dairy farm was taken to hospital
      suffering from bloody diarrhoea. Escherichia coli O157:H7 was isolated from her
      stool. Initial tests of well water samples were negative for E. coli by standard
      methods but culture of selected coliform colonies on sorbitol-MacConkey agar led
      to isolation of E. coli O157:H7. E. coli O157:H7 was also isolated from 63% of
      cattle on the farm. The E. coli O157:H7 isolates from the child, the water and
      the cattle were phage type 14, produced verotoxins 1 and 2, and were highly
      related on analysis by pulsed field gel electrophoresis. The child did not have
      known direct contact with the cattle and did not consume unpasteurized milk.
      Hydrogeological investigation revealed the design and location of the well would
      allow manure-contaminated surface water to flow into the well. This investigation
      demonstrates that cattle farm well water is a potential source of E. coli O157:H7
      which may not be identified by standard screening for E. coli in water.

PMID- 9528810
TI  - MEK kinase 1, a substrate for DEVD-directed caspases, is involved in genotoxin
      induced apoptosis.
AB  - MEK kinase 1 (MEKK1) is a 196-kDa protein that, in response to genotoxic agents,
      was found to undergo phosphorylation-dependent activation. The expression of
      kinase-inactive MEKK1 inhibited genotoxin-induced apoptosis. Following activation
      by genotoxins, MEKK1 was cleaved in a caspase-dependent manner into an active 91
      kDa kinase fragment. Expression of MEKK1 stimulated DEVD-directed caspase
      activity and induced apoptosis. MEKK1 is itself a substrate for CPP32 (caspase
      3). A mutant MEKK1 that is resistant to caspase cleavage was impaired in its
      ability to induce apoptosis. These findings demonstrate that MEKK1 contributes to
      the apoptotic response to genotoxins. The regulation of MEKK1 by genotoxins
      involves its activation, which may be part of survival pathways, followed by its
      cleavage, which generates a proapoptotic kinase fragment able to activate
      caspases. MEKK1 and caspases are predicted to be part of an amplification loop to
      increase caspase activity during apoptosis.

PMID- 9528814
TI  - Occurrence of shigatoxinogenic Escherichia coli O157 in Norwegian cattle herds.
AB  - To investigate if there is a reservoir of Escherichia coli O157 in Norwegian
      cattle, faecal samples from 197 cattle herds were screened for E. coli O157 by
      the use of immunomagnetic separation (IMS) and PCR during the 1995 grazing
      season. Six E. coli O157:H-isolates were detected in two herds, one isolate in
      one and five in the other. The isolates carried the stx1, stx2, and eae genes,
      and a 90 MDa virulence plasmid. They were toxinogenic in a Vero cell assay. From
      57 other herds, 137 faecal samples were positive for stx1 and/or stx2 genes
      detected by PCR run directly on IMS-isolated material. Among these samples, stx2
      were the most widely distributed toxin encoding genes. No difference was found
      among milking cows and heifers in the rate of stx1 and/or stx2 in positive
      samples.

PMID- 9528815
TI  - A community outbreak of Salmonella berta associated with a soft cheese product.
AB  - In September 1994, a complaint was registered at a public health unit concerning
      a cheese product. In addition, public health laboratories in Ontario reported an
      increase in the number of isolates of Salmonella berta from patients with
      diarrhoeal illness. A clinical, environmental and laboratory investigation was
      initiated to determine the nature of this outbreak. Isolates of Salmonella berta
      were compared using large fragment genomic fingerprinting by pulsed-field gel
      electrophoresis (PFGE). By late October, 82 clinical cases had been identified
      including 35 confirmed, 44 suspected and 3 secondary. The investigation linked
      illness to consumption of an unpasteurized soft cheese product produced on a farm
      and sold at farmers' markets. Subtyping results of patient, cheese and chicken
      isolates were indistinguishable, suggesting that the cheese was contaminated by
      chicken carcasses during production. The outbreak illustrates the potential role
      of uninspected home-based food producers and of cross-contamination in the
      transmission of foodborne bacterial pathogens.

PMID- 9528816
TI  - Surveillance of outbreaks of waterborne infectious disease: categorizing levels
      of evidence.
AB  - Public health surveillance requires the monitoring of waterborne disease, but
      sensitive and specific detection of relevant incidents is difficult. The
      Communicable Disease Surveillance Centre receives information from various
      sources about clusters of cases of illness in England and Wales. The reporter may
      suspect that water consumption or recreational water exposure is the route of
      infection, or subsequent investigation may raise the hypothesis that water is
      associated with illness. It is difficult to prove beyond reasonable doubt that
      such a hypothesis is correct. Water samples from the time of exposure are seldom
      available, some organisms are difficult to detect and almost everyone has some
      exposure to water. Therefore, we have developed a method of categorizing the
      degree of evidence used to implicate water. The categories take into account the
      epidemiology, microbiology and water quality information. Thus outbreaks are
      classified as being associated with water either 'strongly', 'probably' or
      'possibly'. This system allows a broad database for monitoring possible effects
      of water and is not confined to the few outbreaks which have been intensively
      investigated or have positive environmental microbiology. Thus, for reported
      incidents, the sensitivity of classifying it as water associated should be high
      but this may be at the expense of specificity, especially with the 'possible'
      association.

PMID- 9528817
TI  - Surveillance data for waterborne illness detection: an assessment following a
      massive waterborne outbreak of Cryptosporidium infection.
AB  - Following the 1993 Milwaukee cryptosporidiosis outbreak, we examined data from
      eight sources available during the time of the outbreak. Although there was a
      remarkable temporal correspondence of surveillance peaks, the most timely data
      involved use of systems in which personnel with existing close ties to public
      health programmes perceived the importance of providing information despite
      workload constraints associated with an outbreak. During the investigation,
      surveillance systems which could be easily linked with laboratory data, were
      flexible in adding new variables, and which demonstrated low baseline variability
      were most useful. Geographically fixed nursing home residents served as an ideal
      population with nonconfounded exposures. Use of surrogate measurements of
      morbidity can trigger worthwhile public health responses in advance of laboratory
      confirmed diagnosis and help reduce total morbidity associated with an outbreak.
      This report describes the relative strengths and weaknesses of these surveillance
      methods for community-wide waterborne illness detection and their application in
      outbreak decision making.

PMID- 9528818
TI  - Foodborne outbreaks of hepatitis A in a low endemic country: an emerging problem?
AB  - This paper describes 2 outbreaks of hepatitis A infection in Finland, a very low
      endemic area of hepatitis A infection, where a large proportion of the population
      is now susceptible to infection by hepatitis A virus (HAV). The first outbreak
      involved people attending several schools and day-care centres; the second
      employees of several bank branches in a different city. The initial investigation
      revealed that both were related to food distributed widely from separate central
      kitchens. Two separate case-control studies implicated imported salad food items
      as the most likely vehicle of infection. HAV was detected in the stool of cases
      from both outbreaks using reverse-transcriptase polymerase chain reaction;
      however, comparison of viral genome sequences proved that the viruses were of
      different origin and hence the outbreaks, although occurring simultaneously, were
      not linked. Foodborne outbreaks of HAV may represent an increasing problem in
      populations not immune to HAV.

PMID- 9528819
TI  - Identification of two antigenically and genetically distinct lineages of H3N8
      equine influenza virus in Sweden.
AB  - Four Swedish strains of equine H3N8 influenza virus isolated from outbreaks
      during the last 4 years were characterized. Antigenic typing using monoclonal
      antibodies raised against a variety of H3N8 strains showed that the viruses are
      heterogeneous, the 1993 isolate being closely related to the 1991 Swedish isolate
      TAB/91 and the other three isolates from 1994 and 1996 being more closely related
      to each other. This pattern is reflected in the phylogenetic data calculated from
      nucleotide sequencing of the haemagglutinin genes. H3N8 equine influenza can be
      seen to be evolving in two distinct lineages, one European and one American. The
      1993 isolate is closely related to the European lineage and is the most recent
      Swedish strain of this lineage to be isolated. The 1994 and 1996 isolates fit
      into the American lineage, which contains recent isolates from the United States
      and also Britain. These results indicate that American-type H3N8 viruses have
      become endemic in Sweden and, in light of the antigenic differences which can be
      observed between viruses belonging to the two lineages, we believe that equine
      influenza virus vaccines should be updated with an American-type virus strain.

PMID- 9528820
TI  - Estimation of the effect of neutropenia on rates of clinical bacteraemia in HIV
      infected patients.
AB  - A retrospective cohort study was conducted to quantitate the relationship between
      neutropenia and rates of clinical bacteraemia among adults with HIV infection
      receiving medical care at one institution between 1991-5. The primary exposure,
      absolute neutrophil count (ANC), was summarized as mean ANC within a given week,
      using a five-level stratification (reference > 1000/microl). ANC stratum-specific
      rates of bacteraemia were calculated, by organism type. Linear trend tests were
      performed to assess dose-response relationship between neutropenia and rates of
      bacteraemia. The cohort included 1645 patients contributing 26,785 patients-weeks
      and 191 episodes of bacteraemia. The unadjusted effect of neutropenia was most
      evident for bacteraemia due to E. coli (RR 3.4), Klebsiella pneumoniae (RR 16.7),
      and P. aeruginosa (RR 10.4). For bacteraemia due to any of these three organisms
      (47 episodes), with reference ANC > 1000/microl, relative rates were: 751
      1000/microl, 1.12; 501-750/microl, 2.11; 251-500/microl, 13.58; 0-250/microl,
      21.89.

PMID- 9528821
TI  - Parasitic infections among Southeast Asian labourers in Taiwan: a long-term
      study.
AB  - Parasitic infections have been reported to be relatively common among the
      Southeast Asian labourers in Taiwan. This study, conducted in 1992-6, was
      designed to determine the temporal changes of the prevalence. Faecal specimens
      were examined by the formalin-ethyl acetate sedimentation technique and blood
      samples screened using the quantitative buffy coat technique and confirmed by
      Giemsa stained blood smear. The overall prevalence of intestinal parasitic
      infections was 10.3%. The annual prevalence decreased from 33.3% in 1992-3 to
      4.6% in 1995-6. The Thai (12.0%) and Indonesian (11.1%) had a higher prevalence
      than the Malaysian (6.7%) and Filipinos (5.9%). Opisthorchis viverrini was the
      most important parasite in the Thai and Trichuris trichiura in the remaining
      groups. Moreover, no blood parasites were found in the labourers. The dramatic
      temporal decline in the intestinal parasitic infections suggests that limiting
      the entry of infected persons, periodic follow-ups, and immediate treatment of
      sporadic cases are necessary in preventing transmission of non-indigenous
      parasites through large population change.

PMID- 9528822
TI  - Prevalence of Toxoplasma gondii specific immunoglobulin G antibodies among
      pregnant women in Norway.
AB  - During one year from June 1992 serum IgG antibodies to Toxoplasma gondii among
      35,940 pregnant women were measured in a cross-sectional study conducted in
      Norway. The overall prevalence was 10.9%. The lowest prevalences were detected in
      the north (6.7%) and in the inland counties (8.2%). A significantly higher
      prevalence was detected in the southern counties (13.4%) where a mild, coastal
      climate prevails. Women with foreign names had a higher prevalence (22.6%) than
      women with Norwegian names (10.0%). The high prevalence among women living in the
      capital city (Oslo) as compared to other cities and rural areas (13.2% vs. 10.1%
      and 10.2% respectively), was explained by the higher proportion of foreign women
      in Oslo. Prevalence significantly increased with age in women over 34 years old.
      This increase was only detected among women with Norwegian names. An increase in
      prevalence according to number of children was detected. Women without children
      had a prevalence of 8.8% while women with three children or more had a prevalence
      of 14.9%. Multivariate analyses showed that being seropositive was independently
      associated with county of residence, age, nationality and number of children.

PMID- 9528823
TI  - Chlamydia pneumoniae is a risk factor for coronary heart disease in symptom-free
      elderly men, but Helicobacter pylori and cytomegalovirus are not.
AB  - To test the hypothesis that chronic infection with Chlamydia pneumoniae,
      Helicobacter pylori or cytomegalovirus is associated with coronary heart disease
      risk in elderly men, a nested case-control study in a cohort investigated in 1985
      and 1990 in the town of Zutphen, The Netherlands, was designed. Fifty-four cases
      with a first diagnosed coronary event between 1985 and 1990, and 108 age-matched
      control subjects free of coronary heart disease during follow up were included in
      the study. The overall prevalence of antibodies to cytomegalovirus was 74.7%, to
      H. pylori 75.9% and to C. pneumoniae 84.0%. A high level of antibodies to C.
      pneumoniae was associated with an increased coronary heart disease risk (OR =
      2.76; 95% CI = 1.31-5.81). This association was stronger in cases developing both
      myocardial infarction and angina pectoris, than in cases developing only one of
      these. This association was independent of potential confounders. Antibodies to
      cytomegalovirus or H. pylori were not associated with coronary heart disease
      risk. These results support the hypothesis of a role of chronic C. pneumoniae
      infections in the immunopathogenesis of atherosclerosis.

PMID- 9528824
TI  - Spatial distribution patterns of Echinococcus multilocularis (Leuckart 1863)
      (Cestoda: Cyclophyllidea: Taeniidae) among red foxes in an endemic focus in
      Brandenburg, Germany.
AB  - Over a period of 40 months, 4374 foxes were randomly sampled from an area located
      in northwestern Brandenburg, Germany, and examined parasitologically for
      infections with Echinococcus multilocularis. Spatial analysis of the origin of
      infected animals identified two (one central and one southeastern) high-endemic
      foci with an estimated prevalence of 23.8%. By contrast, a prevalence of 4.9% was
      found in the remaining (low-endemic) area. The prevalences among juvenile and
      adult foxes were compared in the high-endemic and the low-endemic areas. To
      analyse the central high-endemic focus further, the random sample was stratified
      by zones representing concentric circles with a radius of 13 km (zone 1) or x(n
      1) + 7 km for the remaining three zones from the apparent centre of this focus
      (anchor point). Prevalences calculated for each zone showed a decrease from zone
      1 (18.8%) to zone 4 (2.4%) with significant differences for all zones but zones 3
      and 4. The relative risk of an infection decreased rapidly in a distance range of
      26 km around the high-endemic focus, whereas the relative risk remained unchanged
      within a distance of 5 km around the anchor point. The importance of
      heterogeneous spatial distribution patterns for the diagnosis and epidemiology of
      the infection is discussed.

PMID- 9528825
TI  - Epidermal growth factor receptor activation in androgen-independent but not
      androgen-stimulated growth of human prostatic carcinoma cells.
AB  - These studies were undertaken to assess the relative expression and autocrine
      activation of the epidermal growth factor receptor (EGFR) in normal and
      transformed prostatic epithelial cells and to determine whether EGFR activation
      plays a functional role in androgen-stimulated growth of prostate cancer cells in
      vitro. EGFR expression was determined by Western blot analysis and ELISA
      immunoassays. Immunoprecipitation of radiophosphorylated EGFR and evaluation of
      tyrosine phosphorylation was used to assess EGFR activation. The human androgen
      independent prostate cancer cell lines PC3 and DU145 exhibited higher levels of
      EGFR expression and autocrine phosphorylation than normal human prostatic
      epithelial cells or the human androgen-responsive prostate cancer cell line
      LNCaP. PC3 and DU145 cells also showed higher levels of autonomous growth under
      serum-free defined conditions. Normal prostatic epithelial cells expressed EGFR
      but did not exhibit detectable levels of EGFR phosphorylation when cultured in
      the absence of exogenous EGF. Addition of EGF stimulated EGFR phosphorylation and
      induced proliferation of normal cells. LNCaP cells exhibited autocrine
      phosphorylation of EGFR but did not undergo significant proliferation when
      cultured in the absence of exogenous growth factors. A biphasic growth curve was
      observed when LNCaP cells were cultured with dihydrotestosterone (DHT). Maximum
      proliferation occurred at 1 nM DHT with regression of the growth response at DHT
      concentrations greater than 1 nM. However, neither EGFR expression nor
      phosphorylation was altered in LNCaP cells after androgen stimulation. In
      addition, DHT-stimulated growth of LNCaP cells was not inhibited by anti-EGFR.
      These studies show that autocrine activation of EGFR is a common feature of
      prostatic carcinoma cells in contrast to normal epithelial cells. However, EGFR
      activation does not appear to play a functional role in androgen-stimulated
      growth of LNCaP cells in vitro.

PMID- 9528826
TI  - The retinoblastoma protein-associated cell cycle arrest in S-phase under moderate
      hypoxia is disrupted in cells expressing HPV18 E7 oncoprotein.
AB  - We have studied the role of the oxygen-dependent pyrimidine metabolism in the
      regulation of cell cycle progression under moderate hypoxia in human cell lines
      containing functional (T-47D) or non-functional (NHIK 3025, SAOS-2)
      retinoblastoma gene product (pRB). Under aerobic conditions, pRB exerts its
      growth-regulatory effects during early G1 phase of the cell cycle, when all pRB
      present has been assumed to be in the underphosphorylated form and bound in the
      nucleus. We demonstrate that pRB is dephosphorylated and re-bound in the nucleus
      in approximately 90% of T-47D cells located in S and G2 phases under moderately
      hypoxic conditions. Under these conditions, no T-47D cells entered S-phase, and
      no progression through S-phase was observed. Progression of cells through G2 and
      mitosis seems independent of their functional pRB status. The p21WAF1/CIP1
      protein level was significantly reduced by moderate hypoxia in p53-deficient T
      47D cells, whereas p16(INK4a) was not expressed in these cells, suggesting that
      the hypoxia-induced cell cycle arrest is independent of these cyclin-dependent
      kinase inhibitors. The addition of pyrimidine deoxynucleosides did not release T
      47D cells, containing mainly underphosphorylated pRB, from the cell cycle arrest
      induced by moderate hypoxia. However, NHIK 3025 cells, in which pRB is abrogated
      by expression of the HPV18 E7 oncoprotein, and SAOS-2 cells, which lack pRB
      expression, continued cell cycle progression under moderate hypoxia provided that
      excess pyrimidine deoxynucleosides were present. NHIK 3025 cells express high
      levels of p16INK4a under both aerobic and moderately hypoxic conditions,
      suggesting that the inhibitory function of p16(INK4a) would not be manifested in
      such pRB-deficient cells. Thus, pRB, a key member of the cell cycle checkpoint
      network, seems to play a major role by inducing growth arrest under moderate
      hypoxia, and it gradually overrides hypoxia-induced suppression of pyrimidine
      metabolism in the regulation of progression through S-phase under such
      conditions.

PMID- 9528827
TI  - Influence of pH on the uptake of 5-fluorouracil into isolated tumour cells.
AB  - To investigate the possible dependence of 5-fluorouracil (5FU) uptake in tumours
      on the intra- (pHi) and extracellular (pHe) pH, a pH gradient (deltapH) was
      imposed across the plasma membrane of ascites tumour cells in vitro, similar to
      that known to occur in some solid tumours in vivo, by incubation in media of PHe
      5-8. A > or = 2:1 (intracellular/extracellular) accumulation of radiolabelled 5FU
      occurred after 5 min incubation of the cells with 0.5 mM 5FU at pHe of 5.0, 5.5
      or 6.0. 5FU metabolism is slow under these conditions, and 5FU uptake was not
      affected by longer incubations up to 20 min, nor by the absence of a sodium
      gradient. pHi was estimated from the distribution of the weak acid, 5.5-dimethyl
      2,4-oxazolidione ([14C]DMO) across the cell membrane. There was significant
      correlation between the intracellular/extracellular 5FU ratio and pHe (from pHe 6
      8), deltapH and pHi (P < 0.02). Similar results were obtained with HT29 cells.
      Incubation with a drug that made plasma membranes permeable to H+ significantly
      decreased 5FU uptake in Lettre cells. The co-transport of 5FU may occur on a
      proton symport using the proton motive force of the deltapH.

PMID- 9528828
TI  - Captopril inhibits tumour growth in a xenograft model of human renal cell
      carcinoma.
AB  - The effect of captopril on tumour growth was examined in a xenograft model of
      human renal cell carcinoma (RCC). Inoculation of the human RCC cell line SN12K-1
      (10(6) cells) under the left kidney capsule of severe combined immunodeficient
      (SCID) mice resulted in the growth of large tumours, with an increase in weight
      of the inoculated kidney of 3.69+/-1.63-fold (mean+/-s.d.) when compared with the
      contralateral normal kidney. In mice treated with captopril (19 mg kg(-1) day(-1)
      or 94 mg kg(-1) day(-1) administered in the drinking water), there was a
      significant dose-related reduction in tumour development; the tumour bearing
      kidneys weighed 1.9+/-0.42 and 1.55+/-0.42 times the normal kidneys, respectively
      (P< 0.05 compared with untreated animals). In vitro, captopril at clinically
      achievable doses (0.1-10 microM) had no significant effect on the incorporation
      of [3H]thymidine into SN12K-1 cells. Thus, this highly significant attenuation by
      captopril of in vivo tumour growth does not appear to be due to a direct effect
      on the proliferation of the tumour cells. Further studies are required to
      determine the mechanism of inhibition of tumour growth by captopril, in
      particular to evaluate the role of angiotensin II in this process.

PMID- 9528829
TI  - Timing of recombinant human granulocyte colony-stimulating factor administration
      on neutropenia induced by cyclophosphamide in normal mice.
AB  - The effects of altering the timing of recombinant human granulocyte colony
      stimulating factor (rhG-CSF) administration on neutropenia induced by
      cyclophosphamide (CPA) were studied experimentally in a mouse model. Experimental
      mice were divided into three groups: (a) treatment with rhG-CSF after CPA
      administration (post-treatment group); (b) treatment with rhG-CSF both before and
      after CPA administration (pre- and post-treatment group); and (c) treatment with
      saline after CPA administration (control group). The results were as follows.
      Mice receiving rhG-CSF on the 2 days preceding CPA treatment, in which progenitor
      cell counts outside the S-phase when CPA was administered were the lowest of all
      the groups, showed accelerated neutrophil recovery but decreased neutrophil
      nadirs compared with the control group despite rhG-CSF treatment. The pre- and
      post-treatment group, consisting of mice who received rhG-CSF treatment on days 
      4 and -3 before CPA treatment, and in which progenitor cell counts when CPA was
      administered were increased to greater levels than in the other groups, showed
      remarkably accelerated neutrophil recovery and the greatest increase in the
      neutrophil nadirs of all the groups. These results suggested that the kinetics of
      progenitor cell populations when chemotherapeutic agents were administered seemed
      to play an important role in neutropenia after chemotherapy, and that not only
      peripheral neutrophil cell and total progenitor cell counts but also progenitor
      cell kinetics should be taken into consideration when administering rhG-CSF
      treatment against the effects of chemotherapy.

PMID- 9528830
TI  - Syndecan-1 is up-regulated in ras-transformed intestinal epithelial cells.
AB  - The syndecans, a family of cell-surface heparan sulphate proteoglycans, have been
      proposed to mediate cellular interactions with extracellular effector molecules,
      such as growth factors and components of the extracellular matrix, during
      critical phases of development. Transcripts of all four syndecans are expressed
      at varying levels in the developing rat intestine and in a series of immature rat
      intestinal epithelial cell lines. In addition, we report the novel finding that,
      in the intestinal epithelial cell lines, expression of syndecan-1 transcript is
      up-regulated by transformation with activated H-ras. This is in contrast to other
      cell lines in which ras transformation is associated with a decrease in syndecan
      1 levels. The observed increase in the syndecan-1 occurs as a result of increased
      transcription and can be correlated with the degree of transformation of the IEC
      18 cells. Transformation is also associated with a decrease in apparent molecular
      weight and increased shedding of the proteoglycan into the culture medium.
      Increased shedding of syndecan-1 into the culture medium after transformation
      with H-ras may contribute to the disruption of proteoglycan interactions with the
      extracellular matrix, leading to alterations in cell adhesion and organization.

PMID- 9528831
TI  - Hypoxia-induced angiogenesis and vascular endothelial growth factor secretion in
      human melanoma.
AB  - Tumour cells exposed to hypoxia in vitro can show increased expression of several
      selected genes, including the gene encoding the vascular endothelial growth
      factor (VEGF), suggesting that hypoxia followed by reoxygenation might promote
      the malignant progression of tumours. An in vitro/in vivo study was conducted to
      investigate whether hypoxia can increase the angiogenic potential of tumour cells
      through increased VEGF secretion. Four human melanoma cell lines (A-07, D-12, R
      18, U-25) were included in the study. Cell cultures were exposed to hypoxia
      (oxygen concentration <10 p.p.m.) in vitro using the steel chamber method. Rate
      of VEGF secretion was measured in vitro in aerobic and hypoxic cell cultures by
      ELISA. Angiogenesis was assessed in vivo using the intradermal angiogenesis
      assay. Aliquots of cells harvested from aerobic cultures or cultures exposed to
      hypoxia for 24 h were inoculated intradermally in the flanks of adult female
      BALB/c-nu/nu mice. Tumours developed and angiogenesis was quantified by scoring
      the number of capillaries in the dermis oriented towards the tumours. The number
      of tumour-oriented capillaries did not differ significantly between tumours from
      hypoxic and aerobic cultures for A-07 and U-25, whereas tumours from hypoxic
      cultures showed a larger number of tumour-oriented capillaries than tumours from
      aerobic cultures for D-12 and R-18. The VEGF secretion under aerobic conditions
      and the absolute increase in VEGF secretion induced by hypoxia were lower for D
      12 and R-18 than for A-07 and U-25, whereas the relative increase in VEGF
      secretion induced by hypoxia was higher for D-12 and R-18 than for A-07 and U-25.
      VEGF is not a limiting factor in the angiogenesis of some tumours under normoxic
      conditions. Hypoxia can increase the angiogenic potential of tumour cells by
      increasing the secretion of VEGF, but only of tumour cells showing low VEGF
      secretion under normoxia. Transient hypoxia might promote the malignant
      progression of tumours by temporarily increasing the angiogenic potential of
      tumour cells showing low VEGF expression under normoxic conditions.

PMID- 9528832
TI  - Expression of Ret/PTC1, -2, -3, -delta3 and -4 in German papillary thyroid
      carcinoma.
AB  - Ret/PTC oncogene has been described with a frequency of 2.5-30% in papillary
      thyroid carcinomas. We examined the expression of ret/PTC in 99 German papillary
      thyroid carcinomas, including two recently described new variants of ret/PTC3 and
      identified eight ret/PTC-positive tumours (8%) but none with the new variants.

PMID- 9528833
TI  - Interleukin 6 and its relationship to clinical parameters in patients with
      malignant pleural mesothelioma.
AB  - The relationship between interleukin 6 (IL-6) levels and clinical parameters was
      studied in 25 patients with malignant pleural mesothelioma. The serum levels of
      IL-6, C-reactive protein, alpha1-acid glycoprotein and fibrinogen were
      significantly higher in mesothelioma than in lung adenocarcinoma with cytology
      positive pleural effusion. Serum IL-6 levels correlated with the levels of the
      acute-phase proteins. We demonstrated a high incidence of thrombocytosis (48%)
      and a significant correlation between platelet count and the serum IL-6 level.
      The level of IL-6 in the pleural fluid of patients with mesothelioma was
      significantly higher than in the pleural fluid of patients with adenocarcinoma,
      and was about 60-1400 times higher than in the serum. However, even higher levels
      of IL-6 in the pleural fluid and of thrombocytosis were found in patients with
      tuberculous pleurisy. These results indicate that large amounts of IL-6 from the
      pleural fluid of patients with mesothelioma leak into the systemic circulation
      and induce clinical inflammatory reactions. These profiles are not specific to
      mesothelioma as similar profiles are found in patients with tuberculous pleurisy.
      However, the detection of a markedly increased level of IL-6 in pleural fluid
      argues against a diagnosis of adenocarcinoma.

PMID- 9528834
TI  - N-acetyl transferase 1: two polymorphisms in coding sequence identified in
      colorectal cancer patients.
AB  - Increased cancer risk has been associated with functional polymorphisms that
      occur within the genes coding for the N-acetyltransferase enzymes NAT1 and NAT2.
      We detected two NAT1 polymorphisms in colorectal cancer patients by heteroduplex
      analysis. DNA sequencing revealed the wild-type sequence (NAT1*4) and two single
      base substitutions at adjacent positions 999 bp (C to T, NAT1*14) and 1000 bp (G
      to A, NAT1*15) of the gene, changing Arg187 to a stop codon and Arg187 to Gln
      respectively. NAT1 alleles NAT1*4 (0.98) and NAT1*15 (0.02) were present at a
      similar frequency in patients with colorectal cancer (n=260) and in a Scottish
      control group (n=323). The third allele, NAT1*14, was present only in the
      colorectal cancer group at a frequency of 0.006. NAT1 genotype NAT1*4/ NAT1*15
      was significantly less frequent in individuals that had a slow NAT2 genotype.
      This was observed in both cancer and control groups and suggests that this
      association was unrelated to cancer risk. We conclude that polymorphisms within
      the coding region of the NAT1 gene are infrequent and do not appear to have an
      independent association with colorectal cancer risk. However, the relationship
      between NAT1 and NAT2 polymorphisms appears non-random, suggesting a linkage
      between these enzymes.

PMID- 9528835
TI  - Systematic heterogeneity and prognostic significance of cell proliferation in
      colorectal cancer.
AB  - The prognosis of colorectal cancer has not significantly changed during the last
      30 years. While evaluation of tumour cell proliferation may provide prognostic
      information, results obtained so far have been contradictory Heterogeneity in
      tumour cell proliferation may explain these contradictions. With in vivo
      injection of iododeoxyuridine (IdUrd), estimation of labelling index (LI), S
      phase transit time (Ts) and potential doubling time (Tpot) may be performed from
      a single sample. A total of 109 colorectal cancers were studied after in vivo
      injection of IdUrd before surgical removal. From each cancer, four to eight
      samples were processed for both flow cytometrical (FCM) and immunohistochemical
      (IHC) visualization of IdUrd incorporation. LI/IHC was morphometrically
      quantified at both the luminal border and the invasive margin of these tumours.
      LI was significantly higher at the luminal border compared with the invasive
      margin, although they were correlated with each other. Using combined IHC and FCM
      methods, rapidly growing colorectal cancers (high LI and/or low Tpot) showed an
      increased survival (significant for LI at the invasive margin and for Tpot at
      both the invasive margin and the luminal border) in the entire unselected
      material and for radically removed Dukes' B tumours. FCM data alone did not
      discriminate for survival, with the exception of Ts in diploid and radically
      removed Dukes' B tumours.

PMID- 9528836
TI  - Assay of matrix metalloproteinases types 1, 2, 3 and 9 in breast cancer.
AB  - Matrix metalloproteinases (MMPs) are zinc dependent endopeptidases implicated in
      cancer invasion and metastasis. Gelatin zymography was performed on 84 human
      breast carcinomas and seven normal breast tissues. The precursor form of MMP-2
      (72 kDa) was found in 11 (12%) samples, while its two activated forms, i.e. 62
      kDa and 59 kDa, were found in three (6%) and 34 (40%) samples respectively. In
      contrast to MMP-2, most of the samples (52%) contained MMP-9 in its precursor
      form. Using ELISA, MMP-1 levels were found in 12% of the samples while MMP-3
      levels were found in only 2% of the samples. Levels of MMP-2, -3 and -9
      correlated inversely with numbers of nodal metastases. Neither MMP-2 nor -9
      levels were significantly related to patient outcome. However, patients with high
      levels of a 50-kDa gelatinase band after zymography had a significantly better
      survival than patients with low levels. This species was never observed in normal
      breast tissue.

PMID- 9528838
TI  - Correlation between basic fibroblast growth factor immunostaining of stromal
      cells and stromelysin-3 mRNA expression in human breast carcinoma.
AB  - We examined the localization of basic fibroblast growth factor (bFGF) in a series
      of human breast carcinomas using immunohistochemistry. Staining was observed in
      tumour cells in 15 out of 54 (28%) tumours and in the adjacent stroma in 34 out
      of 54 (63%) tumours examined. No correlation was observed between positive
      staining of these two compartments. The relationship between bFGF staining and
      expression of the metalloprotease stromelysin-3, and between bFGF and microvessel
      density, was examined. A statistically significant correlation (P < 0.003) was
      observed between bFGF staining of the stromal compartment and high expression of
      stromelysin-3 (ST-3; MMP-11) metalloprotease mRNA by stromal cells. In contrast,
      no correlation was observed between bFGF and intratumour microvessel density
      (IMD). These results raise the possibility that bFGF may be involved in the
      induction of stromelysin-3 mRNA expression in breast cancer stroma.

PMID- 9528837
TI  - Prognostic significance of urokinase-type plasminogen activator and plasminogen
      activator inhibitor-1 in primary breast cancer.
AB  - The uPA-mediated pathway of plasminogen activation is central to cancer
      metastasis. Whether uPA and PAI-1 are related to local recurrence, metastatic
      spread or both is not clear. We present a retrospective study of 429 primary
      breast cancer patients with a median follow-up of 5.1 years, in which the levels
      of uPA and PAI-1 in tumour extracts were analysed by means of an enzyme-linked
      immunosorbent assay. The median values of uPA and PAI-1, which were used as cut
      off points, were 4.5 and 11.1 ng mg(-1) protein respectively. The levels of uPA
      and PAI-1 were correlated with tumour size, degree of anaplasia, steroid receptor
      status and number of positive nodes. Patients with high content of either uPA or
      PAI-1 had increased risk of relapse and death. We demonstrated an independent
      ability of PAI-1 to predict distant metastasis (relative risk 1.7, confidence
      limits 1.22 and 2.46) and that neither uPA nor PAI-1 provided any information
      regarding local recurrence.

PMID- 9528839
TI  - Heterogeneity in microvascular density in lung tumours: comparison with normal
      bronchus.
AB  - The aim of this study was to test the hypotheses that (a) microvascular density
      (MVD) measured in histological sections of resected non-small cell lung
      carcinomas is an index of angiogenesis and (b) the measurement of MVD in a single
      block is representative of the overall MVD of the tumour. MVD was quantitated in
      one block per specimen of 60 lung tumours and nine normal lung tissues, and in 47
      blocks taken from different regions of four tumours. Blood vessels were stained
      with antibody to von Willebrand Factor and MVD was quantitated using two methods:
      average density throughout the section (a-MVD) and density in the most
      vascularized area or 'hot spot' (h-MVD). Similar h-MVD values were found in
      tumours and in normal bronchus, whereas a-MVD was greater in the latter (P <
      0.01). When 47 blocks from four tumours were analysed, inter-tumour variation was
      significant (P < 0.001) in spite of significant intra-tumour variation. The
      highest MVD value was not necessarily found in the periphery of the tumour. The
      four tumours were ranked into either two or four tiers according to their overall
      MVD. In 50 random selections of one block per tumour, the correct ranking was
      achieved in 68-74% of cases with the two-tier ranking and in 6-16% of cases with
      the four-tier ranking (h-MVD and a-MVD values respectively). These results
      suggest that elevated MVD values do not necessarily represent angiogenesis in non
      small cell lung carcinomas. When only one block per tumour is examined, the
      chance of obtaining an accurate estimate of the vascularity of that tumour may be
      lower than 68%.

PMID- 9528840
TI  - Absence of RAS and p53 mutations in thyroid carcinomas of children after
      Chernobyl in contrast to adult thyroid tumours.
AB  - Thyroid carcinomas of an additional series of 34 children exposed to radioactive
      fall-out after the Chernobyl reactor accident were analysed for mutations in the
      H-, K- and N-RAS and the p53 gene. Allele-specific oligonucleotide hybridization,
      single-strand conformation polymorphism (SSCP) and direct sequencing did not
      disclose mutations in codons 12, 13 and 61 of RAS genes nor mutations in exons 5,
      7 and 8 of p53. Considering the recently reported high prevalence of RET
      rearrangements of the PTC3 type in childhood tumours after Chernobyl (Klugbauer
      et al, 1995, Oncogene 11: 2459-2467), it follows that RET rearrangements are the
      most relevant molecular aberration in these radiation-induced tumours. RAS or p53
      mutations do not play a role in childhood thyroid carcinogenesis after Chernobyl.

PMID- 9528841
TI  - Release of the angiogenic cytokine vascular endothelial growth factor (VEGF) from
      platelets: significance for VEGF measurements and cancer biology.
AB  - Vascular endothelial growth factor (VEGF) is a potent angiogenic factor with a
      key role in several pathological processes, including tumour vascularization. Our
      preliminary observations indicated higher VEGF concentrations in serum samples
      than in matched plasma samples. We have now demonstrated that this difference is
      due to the presence of VEGF within platelets and its release upon their
      activation during coagulation. In eight healthy volunteers, serum VEGF
      concentrations ranged from 76 to 854 pg ml(-1) and were significantly higher (P <
      0.01) than the matched citrated plasma VEGF concentrations, which ranged from < 9
      to 42 pg ml(-1). Using platelet-rich plasma, mean (s.d.) platelet VEGF contents
      of 0.56 (0.36) pg of VEGF 10(-6) platelets were found. Immunocytochemistry
      demonstrated the cytoplasmic presence of VEGF within megakaryocytes and other
      cell types within the bone marrow. From examination of the effects of blood
      sample processing on circulating VEGF concentrations, it is apparent that for
      accurate measurements, citrated plasma processed within 1 h of venepuncture
      should be used. Serum is completely unsuitable. The presence of VEGF within
      platelets has implications for processes involving platelet and endothelial cell
      interactions. e.g. wound healing, and in tumour metastasis, when platelets
      adhering to circulating tumour cells may release VEGF at points of adhesion to
      endothelium, leading to hyperpermeability and extravasation of cells.

PMID- 9528842
TI  - The photodynamic response of two rodent tumour models to four zinc (II)
      substituted phthalocyanines.
AB  - Four novel zinc (II)-substituted phthalocyanines, varying in charge and
      hydrophobicity, were evaluated in vivo as new photosensitizers for photodynamic
      therapy. Two rat tumours with differing vascularity were used: a mammary
      carcinoma (LMC1) and a fibrosarcoma (LSBD1), with vascular components six times
      higher in the latter (10.8%+/-1.5) than in the former (1.8%+/-1.4). Each
      sensitizer was assessed for tumour response relative to normal tissue damage, and
      optimum doses were selected for further study, ranging from 0.5 to 20 mg kg(-1).
      Interstitial illumination of the tumours was carried out using a 200-microm-core
      optical fibre with a 0.5 cm length of diffusing tip, at either 680 or 692 nm,
      depending on the sensitizer. Light doses of between 200 and 600 J were delivered
      at a rate of 100 mW from the 0.5-cm diffusing section of the fibre. Maximum mean
      growth delays ranged from 9 to 13.5 days depending on sensitizer and type of
      tumour, with the most potent photosensitizer appearing to be the cationic
      compound. Histopathological changes were investigated after treatment to
      determine the mechanism by which tumour necrosis was effected. The tumours had
      the appearance of an infarct and, under the conditions used, the observed damage
      was shown to be mainly due to ischaemic processes, although some direct tumour
      cell damage could not be ruled out.

PMID- 9528843
TI  - Raltitrexed (Tomudex): an alternative drug for patients with colorectal cancer
      and 5-fluorouracil associated cardiotoxicity.
AB  - Two patients with proven 5-fluorouracil (5-FU)-associated cardiotoxicity were
      treated with the specific thymidylate synthase inhibitor raltitrexed safely,
      without evidence of cardiotoxicity. Raltitrexed might be an alternative for
      patients with advanced colorectal cancer and 5-FU-associated cardiotoxicity. 5-FU
      cardiotoxicity is not due to the antineoplastic mechanisms via thymidilate
      synthase.

PMID- 9528845
TI  - Subjective health estimations (SHE) in patients with advanced breast cancer: an
      adapted utility concept for clinical trials.
AB  - We wished to develop and validate a simple linear analogue self-assessment (LASA)
      scale to assess utility values in multicentre, multicultural breast cancer
      trials. We compared two variants of a LASA scale (score range 0-100) with
      different anchoring points [perfect health to worst possible health (subjective
      health estimation, SHE) and perfect health to death (SHED)] in 84 patients with
      advanced breast cancer. Feasibility was explored in the first 48 patients
      interviewed. Values from the LASA scales were compared with each other and with a
      time trade off (TTO) interview. Scores from the two LASA scales were highly
      correlated (r=0.8, P < 0.0001, Spearman). The relationship between TTO interview
      and SHE was confirmed with tests for trend across ordered groups (linear-trend
      test P < 0.001). Most patients preferred SHE to SHED. SHE scores (in which high
      scores indicate high-health-state values) were significantly different by type of
      treatment, time from diagnosis and age. Thus, significantly different mean SHE
      scores were obtained from patients receiving no treatment or hormone therapy,
      mild and intensive chemotherapy (ANOVA P=0.03) and from patients with diagnosis 2
      years, 2-5 years, 5-10 years and more than 10 years before interview (ANOVA
      P=0.02). Older patients (> 56 years) had a lower mean on the SHE scale (53 vs 61;
      ANOVA P=0.04). We found that the two versions of the LASA scale were equivalent
      for clinical purposes. SHE appeared to provide a feasible, patient-preferred and
      valid alternative to lengthy TTO interviews in assessing the value patients
      attach to their present state of health in large-scale cancer clinical trials.

PMID- 9528844
TI  - The pharmacokinetics and metabolism of ifosfamide during bolus and infusional
      administration: a randomized cross-over study.
AB  - In a randomized cross-over trial, 11 patients received ifosfamide (IFOS) in 21
      day cycles, which alternated between 3 g m(-2) x (2 or 3) days given as a 1-h
      bolus doses, or the same total dose as a continuous infusion. Patients who
      received four or more cycles also alternated between two cycles on dexamethasone
      4 mg 8 hourly for 3 days starting 8 h before IFOS, and two cycles off
      dexamethasone. A total of 34 patient cycles were studied and serum and urinary
      levels of IFOS, 2 dechloroethylifosfamide (2DC), 3 dechloroethylifosfamide (3DC),
      carboxyifosfamide (CX) and isophosphoramide mustard (IPM) were measured by thin
      layer chromatography. No significant differences could be detected in the areas
      under the curve (AUCs) of serum concentration, nor in the proportion of IFOS or
      its metabolites found in the urine. There was no significant effect of
      dexamethasone on IFOS metabolism. These results indicate that there is no
      identifiable pharmacokinetic basis for insistence on either bolus or infusional
      methods of IFOS administration.

PMID- 9528846
TI  - Soluble interleukin-2 receptors (sIL-2R) in Hodgkin's disease: outcome and
      clinical implications.
AB  - The aim of this study was to assess the prognostic role of soluble interleukin-2
      receptors (sIL-2R) in Hodgkin's disease (HD) both in the achievement of complete
      remission (CR) and in predicting disease relapse. Between August 1988 and June
      1993 sIL-2R serum levels were measured in 174 untreated patients; in 137 of them
      evaluation was repeated at the end of treatment and in 132 also during the follow
      up. Baseline sIL-2R levels (mean+/-standard error) were significantly higher in
      patients than in 65 healthy control subjects (1842+/-129 U ml(-1) vs 420+/-10 U
      ml(-10, P< 0.0001). At the end of treatment 135 out of 137 evaluated patients
      achieved complete response (CR) and their mean sIL-2R serum levels were
      significantly lower than those at diagnosis (635+/-19 U ml(-1) vs 1795+/-122 U
      ml(-1), P=0.0001). After a median follow-up of 5 years, sIL-2R remained low in
      114 patients in continuous CR, while they increased in 9 out of 12 patients (75%)
      who relapsed. However, a temporary increase was also observed in six patients
      (5%) still in CR. Treatment outcome in terms of freedom from progression was
      linearly related to sIL-2R levels. Our study confirms that patients with
      untreated HD have increased baseline levels of sIL-2R compared with healthy
      subjects and that their pretreatment values may be an indication of disease
      outcome similar to other conventional prognostic factors, such as number of
      involved sites, presence of B symptoms and extranodal extent.

PMID- 9528848
TI  - Microsatellite instability in female non-small-cell lung cancer patients with
      familial clustering of malignancy.
AB  - There is accumulating evidence of an increased risk of familial clustering of
      cancer in the first-degree relatives of lung cancer probands. However, no
      explanation has been proposed for these epidemiological data. We reviewed 379
      female non-small-cell lung cancer (NSCLC) patients to obtain their family
      histories of malignancy. Among them, nine female NSCLC patients with three or
      more relatives diagnosed with malignancy and 28 control patients without a family
      history of malignancy were selected to be analysed for instability at six
      different microsatellite loci. We observed microsatellite instability (MSI) more
      frequently in the patients with three or more family histories of malignancy (six
      out of nine, 67%) than the control patients (5 out of 28, 18%). The incidence of
      MSI in the former was significantly higher than that in the control (P=0.011:
      Fisher's exact test). We detected no significant difference in
      clinicopathological characteristics between the cases with MSI and those without
      MSI, except for their family histories of cancer. Our results show that a
      significantly higher rate of MSI is associated with familial clustering of
      malignancy. MSI could be one of the underlying mechanisms for familial clustering
      of malignancy in female NSCLC patients.

PMID- 9528847
TI  - Vascular endothelial growth factor (VEGF) mRNA isoform expression pattern is
      correlated with liver metastasis and poor prognosis in colon cancer.
AB  - Vascular endothelial growth factor (VEGF) is a well known factor that induces
      angiogenesis. Four isoforms, i.e. VEGF206, 189, 165, and 121, have been
      identified. We examined the isoform patterns of VEGF mRNA using reverse
      transcription polymerase chain reaction (RT-PCR) analysis in 61 colon cancers.
      All the colon cancers examined expressed VEGF121. The isoform patterns were
      classified into three groups: type 1, VEGF121; type 2, VEGF121 + VEGF165; type 3,
      VEGF121 + VEGF165 + VEGF189. Three of the 61 colon cancers examined showed type 1
      expression, 26 showed type 2 expression and 32 showed the type 3 pattern. The
      patients with liver metastases showed the type 3 isoform expression pattern at a
      significantly higher incidence (12 of 16, 75%) than those without liver
      metastasis (20 of 45, 44%) (P=0.036). The type 3 isoform pattern was
      significantly associated with M1 stage (P=0.019). The patients with colon cancer
      and the type 3 isoform pattern showed significantly poor prognosis (P < 0.01, Cox
      Mantel). The colon cancers with the type 3 pattern showed a significantly higher
      involvement of veins (P=0.006). These observations suggest that the aberrant type
      3 expression pattern of VEGF189 mRNA isoforms is correlated with liver
      metastasis, M stage, and poor prognosis in colon cancer.

PMID- 9528849
TI  - The value of serum alpha-N-acetylgalactosaminidase measurement for the assessment
      of tumour response to radio- and photodynamic therapy.
AB  - Serum activity of alpha-N-acetylgalactosaminidase (NaGalase), the extracellular
      matrix-degrading enzyme that appears to be produced exclusively by cancer cells,
      was measured in mice bearing SCCVII tumours (squamous cell carcinoma). The
      NaGalase levels in these mice increased with time of tumour growth and were
      directly proportional to tumour burden. After exposure of SCCVII tumours to a
      single X-ray dose of 20 Gy, the serum NaGalase levels gradually decreased during
      the first 10 days after treatment (to approximately one-third of the initial
      value) and then began to increase. The decrease in serum NaGalase activity was
      more rapid after the treatment of SCCVII and EMT6 tumours by photodynamic therapy
      (PDT) and was dependent on the PDT dose. The treatments (based on
      photosensitizers Photofrin or mTHPC) that were fully curative resulted in the
      reduction of NaGalase activity to background levels within 2 or 3 days after PDT.
      A slower decrease in NaGalase activity was found after PDT treatments that attain
      an initial tumour ablation but are not fully curative. The regrowth of PDT
      treated SCCVII tumours was preceded by an increase in serum NaGalase levels,
      which was detected as early as 8 days before the visible tumour reappearance.
      These findings ascertain the validity of serum NaGalase measurement for the
      assessment of tumour response to different treatments and support the concept
      that the NaGalase measurement could serve as a diagnostic and prognostic index
      that might allow oncologists to design the dosage or nature of treatment.

PMID- 9528850
TI  - Cross-reactivity between Candida albicans and human ovarian carcinoma as revealed
      by monoclonal antibodies PA10F and C6.
AB  - Summary Antibodies against Candida albicans antigenic determinants have been
      reported to cross-react with human tumour cells. We have found that two
      monoclonal antibodies, C6 and PA1OF, developed at our laboratory against C.
      albicans antigenic determinants, cross-react with human ovarian cancer on Western
      blots and immunohistochemistry. We have subsequently used one of them, PA10OF, to
      test by means of immunohistochemistry a series of 37 human ovarian carcinomas.
      Out of 37 tumours, 25 (67.6%) expressed the antigen recognized by PA1OF. The
      reactivity, however, was concentrated on the subgroup of particularly aggressive,
      invasive carcinomas in advanced stages of the disease (19 out of 24 positive),
      whereas the antigen was expressed significantly less (P=0.0007) in the subgroup
      of much less aggressive stage I tumours of low malignant potential, also called
      borderline carcinomas (2 out of 13 positive). This cross-reactivity between C.
      albicans and ovarian carcinoma seems to be attributable to a common antigenic
      determinant related to tumour aggressiveness.

PMID- 9528851
TI  - Indocyanine green and laser light for the treatment of AIDS-associated cutaneous
      Kaposi's sarcoma.
AB  - Indocyanine green (ICG) is clinically approved for the determination of liver
      function, cardiac output and plasma volume. In this pilot study, ICG was used as
      photosensitizer in combination with a diode laser to treat AIDS-associated
      Kaposi's sarcoma (KS) in three patients. Directly and up to 50 min after
      intravenous administration of ICG (2-4 mg kg(-1) body weight), KS (n=57), mainly
      plaque-type, were irradiated using a diode laser (lambda em=805 nm, 100 J cm[-2],
      0.5-5 W cm[-2]) matching the absorption maximum. Complete remission of KS (n=16)
      was achieved when irradiated 1-30 min after injection of the second dose of ICG
      (2 x 2 mg kg(-1) b.w., 30 min apart) with 3-5 W cm(-2) and 100 J cm(-2). Biopsies
      (n=3) revealed necrosis of the tumour 24 h and complete remission 4 weeks after
      therapy. In general, systemic side-effects were not observed and cosmetic results
      were very good. However, hyperpigmentation occurred temporarily in lesions
      located on the lower extremities. These findings show that AIDS-associated KS can
      be effectively treated after photosensitization with ICG and subsequent
      irradiation with an appropriate diode laser. However, additional investigations
      need to elucidate the exact mechanism of action of ICG-mediated phototherapy and
      have to show the efficacy for the treatment of other highly vascularized solid
      tumours.

PMID- 9528852
TI  - BAP1: a novel ubiquitin hydrolase which binds to the BRCA1 RING finger and
      enhances BRCA1-mediated cell growth suppression.
AB  - We have identified a novel protein, BAP1, which binds to the RING finger domain
      of the Breast/Ovarian Cancer Susceptibility Gene product, BRCA1. BAP1 is a
      nuclear-localized, ubiquitin carboxy-terminal hydrolase, suggesting that
      deubiquitinating enzymes may play a role in BRCA1 function. BAP1 binds to the
      wild-type BRCA1-RING finger, but not to germline mutants of the BRCA1-RING finger
      found in breast cancer kindreds. BAP1 and BRCA1 are temporally and spatially co
      expressed during murine breast development and remodeling, and show overlapping
      patterns of subnuclear distribution. BAP1 resides on human chromosome 3p21.3;
      intragenic homozygous rearrangements and deletions of BAP1 have been found in
      lung carcinoma cell lines. BAP1 enhances BRCA1-mediated inhibition of breast
      cancer cell growth and is the first nuclear-localized ubiquitin carboxy-terminal
      hydrolase to be identified. BAP1 may be a new tumor suppressor gene which
      functions in the BRCA1 growth control pathway.

PMID- 9528853
TI  - Agents that cause DNA double strand breaks lead to p16INK4a enrichment and the
      premature senescence of normal fibroblasts.
AB  - The occurrence of DNA double strand breaks induces cell cycle arrest in mortal
      and immortal human cells. In normal, mortal fibroblasts this block to
      proliferation is permanent. It depends on the growth regulator p53 and a protein
      p53 induces, the cyclin dependent kinase inhibitor, p21. We show here that
      following DNA damage in mortal fibroblasts, the induction of p21 and p53 is to a
      large degree shortlived. By 8 days after a brief exposure to DNA strand breaking
      agents, bleomycin or actinomycin D, p53 protein is at baseline levels, while the
      p53 transactivation level is only slightly above its baseline. By this time the
      concentration of p21 protein, which goes up as high as 100-fold shortly after
      treatment, is down to just 2-4-fold over baseline levels. Following the drop in
      p21 concentration a large increase in the expression level of the tumor
      suppressor gene p16INK4a is observed. This scenario, where a transient increase
      in p21 is followed by a delayed induction of p16INK4a, also happens with the
      permanent arrest that occurs with cellular senescence. In fact, these cells
      treated with agents that cause DNA double strand breaks share a number of
      additional markers with senescent cells. Our findings indicate that these cells
      are very similar to senescent cells and that they have additional factor(s)
      beside p21 and p53 that maintain cell cycle arrest.

PMID- 9528854
TI  - Increased transversions in a novel mutator colon cancer cell line.
AB  - We describe a novel mutator phenotype in the Vaco411 colon cancer cell line which
      increases the spontaneous mutation rate 10-100-fold over background. This mutator
      results primarily in transversion base substitutions which are found infrequently
      in repair competent cells. Of the four possible types of transversions, only
      three were principally recovered. Spontaneous mutations recovered also included
      transitions and large deletions, but very few frameshifts were recovered. When
      compared to known mismatch repair defective colon cancer mutators, the
      distribution of mutations in Vaco411 is significantly different. Consistent with
      this difference, Vaco411 extracts are proficient in assays of mismatch repair.
      The Vaco411 mutator appears to be novel, and is not an obvious human homologue of
      any of the previously characterized bacterial or yeast transversion phenotypes.
      Several hypotheses by which this mutator may produce transversions are presented.

PMID- 9528855
TI  - In vivo degradation of N-myc in neuroblastoma cells is mediated by the 26S
      proteasome.
AB  - N-myc is a short-lived transcription factor, frequently amplified in human
      neuroblastomas. The ubiquitin-proteasome system is involved in the degradation of
      many short-lived cellular proteins and previous studies have shown that ubiquitin
      dependent proteolysis is implicated in the turn-over of N-myc in vitro. However,
      calpain has also been implicated in N-myc degradation in vitro. Here we report
      that, in vivo, N-myc is a sensitive substrate for the 26S proteasome in N-myc
      amplified neuroblastoma cells. We observed that inhibition of the 26S proteasome
      with two inhibitors, ALLnL and lactacystin, led to an elevation of the N-myc
      protein steady-state and increased N-myc protein polyubiquitination, as revealed
      by ubiquitin Western blotting. Pulse-chase experiments have shown that the
      increased N-myc levels resulted from stabilization of the protein. In contrast
      treatment with several calpain and cathepsin inhibitors failed to block N-myc
      degradation in vivo. Furthermore, fluorescence microscopy of ALLnL-treated cells
      localized N-myc exclusively to the nuclear compartment, suggesting the absence of
      a requirement for transport to the cytoplasm prior to degradation.

PMID- 9528856
TI  - Association of an 80 kDa protein with C-CAM1 cytoplasmic domain correlates with C
      CAM1-mediated growth inhibition.
AB  - Decreased expression of C-CAM, a member of the CEA family of immunoglobulin like
      cell adhesion molecules, occurs in carcinomas of the colon, liver and prostate.
      Down regulation of C-CAM during the early stages of carcinogenesis in rat liver
      and human prostate has also been reported. We have recently shown that
      restoration of the expression of the isoform with long cytoplasmic domain, C
      CAM1, leads to suppression of the tumorigenicity of prostatic carcinoma cells in
      vivo and growth suppression in vitro. These observations suggest that C-CAM1 may
      play an important role in regulating cell growth in normal tissues. Previous
      studies have demonstrated that the function of many members of the Ig-supergene
      family is dependent on interactions with cytoplasmic proteins. In the present
      study, we have used a bifunctional cross-linker to identify cellular proteins
      that interact directly with C-CAM1. Immunoblot analysis of WGA bound membrane
      proteins crosslinked with DSS identified a 180 kDa complex composed of C-CAM and
      an 80 kDa protein designated CAP-80 (C-CAM Associated Protein).
      Immunoprecipitation with anti-C-CAM antibodies showed that CAP-80 was co
      precipitated with C-CAM from detergent solubilized, WGA-purified proteins. To
      assess the specificity of CAP-80 binding, the ability of CAP-80 to form stable
      complexes with C-CAM1 mutants expressed in insect cells was tested. Deletion of
      the cytoplasmic domain of C-CAM1 abolished complex formation whereas deletion of
      the extracellular Ig domains had no effect. These results suggest that a CAP-80
      homologue (ICAP-80) is present in insect cells and ICAP-80 interacts with the
      cytoplasmic domain of C-CAM1. Replacement of Tyr488, a residue in the cytoplasmic
      domain known to be phosphorylated in vivo, with Phe did not diminish the
      association between C-CAM1 and ICAP-80, suggesting that Tyr488 phosphorylation is
      not required for association. The ability of various C-CAM1 mutants to associate
      with ICAP-80 correlated with their growth inhibitory activities, suggesting that
      ICAP-80/CAP-80 may play an important role in C-CAM1-mediated growth inhibition.

PMID- 9528858
TI  - CpG methylation within the 5' regulatory region of the BRCA1 gene is tumor
      specific and includes a putative CREB binding site.
AB  - Breast cancer is a genetic disease arising from a series of germ-line and/or
      somatic DNA changes in a variety of genes, including BRCA1 and BRCA2. DNA
      modifications have been shown to occur by a number of mechanisms that include DNA
      methylation. In some cases, the aberrant methylation of CpGs within 5' regulatory
      regions has led to suppression of gene activity. In this report we describe a
      variation in the pattern of DNA methylation within the regulatory region of the
      BRCA1 gene. We found no evidence of methylation at CpGs within the BRCA1 promoter
      in a variety of normal human tissues. However, screening of a series of randomly
      sampled breast carcinomas revealed the presence of CpG methylation adjacent to
      the BRCA1 transcription start site. One such methylated CpG occurs at a putative
      CREB (cAMP-responsive element binding) transcription factor binding site in the
      BRCA1 promoter. Gelshift assays with methylated and unmethylated BRCA1/CREB
      binding site oligonucleotides demonstrate that this site is sensitive to site
      specific CpG methylation. These data suggest that aberrant DNA methylation at
      regulatory sequences in the BRCA1 locus may play a role in the transcriptional
      inactivation of the BRCA1 gene within subclones of breast tumors. This study
      represents the first evidence suggesting a role for DNA methylation in the
      transcriptional inactivation of the BRCA1 in human breast cancer.

PMID- 9528857
TI  - Mmip1: a novel leucine zipper protein that reverses the suppressive effects of
      Mad family members on c-myc.
AB  - C-myc, a member of the basic helix-loop-helix-leucine zipper (bHLH-ZIP) protein
      family activates target genes in heterodimeric association with another bHLH-ZIP
      protein, Max. Max readily homodimerizes, competes with C-myc-Max heterodimers,
      and represses transcription. Four additional bHLH-ZIP proteins, Mad1, Mxi1, Mad3
      and Mad4, heterodimerize with Max and also repress transcription of c-myc
      responsive genes. We employed a yeast two-hybid approach to identify proteins
      which interact with Mxi. We identified a novel ZIP-containing protein, Mmip1 (Mad
      member-interacting protein 1) that strongly dimerizes with all four Mad members,
      but not with c-myc, Max, or with unrelated HLH proteins. The Mmip1-Mxi
      association is mediated by the ZIP domain of each polypeptide and is as strong or
      stronger than the associations between c-myc and Max or Max and Mxi1. In vitro,
      Mmip1 can inhibit DNA binding by Max-Mad heterodimers and, in vivo, can reverse
      the suppressive effects of Mad proteins on c-myc functions. Mmipl is found in a
      variety of cells types, is induced by serum stimulation, and can be co
      immunoprecipitated from fibroblasts in association with Mxi1. By interfering with
      the dimerization between Max and Mad family member proteins, Mmip1 can indirectly
      up-regulate the transcriptional activity of c-myc and suppress the
      antiproliferative actions of Mad proteins.

PMID- 9528859
TI  - p53 binds to a constitutively nucleosome free region of the mdm2 gene.
AB  - The mdm2 oncogene is a p53 responsive gene which contains both a p53 independent
      and a p53 dependent promoter (P1 and P2 respectively). We have utilized ligation
      mediated PCR genomic footprinting in order to investigate the intra-nuclear
      binding of p53 to the mdm2 P2 promoter. The DNase I protection pattern in nuclei
      from murine cells lacking p53 has been compared to the protection pattern in
      cells containing a temperature sensitive p53-Val135. At 32 degrees C p53-Val135
      assumes a wild-type conformation while at 37 degrees C this p53 is
      conformationally mutant. We observed clear wild-type p53 dependent protection of
      the putative p53 response elements (REs) as well as protection of the adjacent
      TATA box. Interestingly the protection pattern observed with purified wild-type
      p53 on naked DNA showed less nucleotide sequence protection than the protection
      observed to be p53 dependent in nuclei. Constitutive DNase I hypersensitivity at
      both the mdm2 P1 and P2 promoters was detected by indirect Southern blot
      analysis. DNase I hypersensitivity reflects altered chromatin conformations
      resulting, most likely, from the absence of nucleosomes. Taken together our
      findings suggest that the mdm2 P2 promoter is maintained in a nucleosome free
      state which is pre-primed for transcriptional activation by p53.

PMID- 9528860
TI  - High prognostic significance of Mdm2/p53 co-overexpression in soft tissue
      sarcomas of the extremities.
AB  - Soft tissue sarcomas are a heterogeneous group of neoplasms with various
      histological subtypes. Up to now, no individual causal molecular markers for
      prognosis and therapeutic success have been identified. A tumorigenic connection
      between the oncogene product Mdm2 and tumor suppressor p53 is generally accepted,
      but their possible clinical relevance has not yet been investigated sufficiently
      in soft tissue sarcoma. In 86 primary soft tissue sarcoma of the extremities (RO
      resected, T1/2 N0 M0), Mdm2 and p53 overexpression were investigated by
      immunohistochemistry. The results were adjusted to clinico-pathological
      characteristics and evaluated for their prognostic relevance by multivariate
      analysis. In Cox's multivariate analysis with stratification of Mdm2 to p53
      results, we determined four groups which had different prognostic values for
      relapse-free and overall survival (Mdm2-/p53- < Mdm2-/p53+ < Mdm2+/p53- <
      Mdm2+/p53+). The most striking finding was a relative risk (rr) for overall
      survival of 18.77 (P=0.006) for patients with Mdm2/p53 co-overexpression (n=40).
      It is noticeably higher than the additive risk from both factors. Coincident
      Mdm2/p53 overexpression is an independent molecular marker with the highest
      prognostic relevance described for soft tissue sarcoma. Thus, a high risk sarcoma
      group has been defined which we believe requires alternative therapeutic
      approaches.

PMID- 9528861
TI  - Nuclear factor - kappaB-dependent regulation of p53 gene expression induced by
      daunomycin genotoxic drug.
AB  - Anthracycline drugs are widely used for the treatment of solid tumors and
      leukemia, but the molecular basis of their biological effect is still poorly
      understood. In the HCT116 colon carcinoma cell line, which retains a wild-type
      inducible p53 gene, we show that the anthracycline daunomycin is a potent inducer
      of p53 and NF-kappaB transcription factors. Nuclear accumulation of p53 protein
      occurred because of increased protein stability and enhanced gene expression. In
      addition, daunomycin induced the p53 promoter through the binding of p50/p65 NF
      kappaB heterodimers to the kappaB site in the p53 promoter. Under our conditions,
      the free radical scavengers NAC and PDTC were not able to block NF-kappaB
      activation or p53 induction, indicating that reactive oxygen intermediates were
      not involved in the cellular response to daunomycin stimulation. Overexpression
      of a stable unresponsive IkappaBalpha mutant in HCT116 cells resulted in a
      complete inhibition of the NF-kappaB activation but only a partial impairment of
      the p53 protein accumulation induced by daunomycin. We conclude that the p53
      activating signal generated by daunomycin is partially regulated by NF-kappaB.

PMID- 9528862
TI  - Inhibition of a naturally occurring EGFR oncoprotein by the p185neu ectodomain:
      implications for subdomain contributions to receptor assembly.
AB  - Mutant Epidermal Growth Factor Receptor (EGFR) oncoproteins lacking most of
      subdomains I and II of the extracellular region, a deletion which includes most
      of the first of two cysteine-rich sequences, have been observed in multiple human
      epithelial tumors, including malignant gliomas. These EGFR oncoproteins,
      designated deltaEGFR or EGFRvIII, confer increased tumorigenicity in vivo and are
      often coexpressed with full-length EGFR in human tumors. We have expressed an
      ectodomain-derived, carboxyl-terminal deletion mutant of the p185neu oncogene
      (T691stop) in human glioblastoma cells coexpressing endogenous EGFR and activated
      deltaEGFR oncoproteins. The p185neu ectodomain-derived mutant forms heterodimers
      with deltaEGFR proteins and reduces the phosphotyrosine content and kinase
      activity of deltaEGFR monomers. As a consequence of T691stop neu expression and
      surface localization, cell proliferation in conditions of full growth and reduced
      serum and anchorage-independent growth in soft agar was reduced in glioblastoma
      cells expressing either endogenous EGFR alone or coexpressing EGFR and elevated
      levels of deltaEGFRs. T691stop neu mutant receptors abrogate the dramatic growth
      advantage conferred by deltaEGFR in vivo, suggesting that physical associations
      primarily between subdomains III and IV of the p185neu and EGFR ectodomains are
      sufficient to modulate signaling from activated EGFR complexes. Receptor-based
      inhibitory strategies exploit the thermodynamic preference for erbB ectodomains
      to heterodimerize, thereby creating erbB receptor assemblies which are defective
      in signaling and do not internalize. Pharmaceuticals which mimic the p185neu
      ectodomain may therefore have important therapeutic applications in advanced
      human malignancies expressing erbB receptors.

PMID- 9528863
TI  - Betacellulin-Pseudomonas toxin fusion proteins bind but are not cytotoxic to
      cells expressing HER4; correlation of EGFR for cytotoxic activity.
AB  - Betacellulin (BTC) is a member of the EGF ligand family that directly binds to
      both EGFR and HER4 and induces the growth of certain epithelial cell types.
      Fusion proteins composed of the terminal 48 or 50 amino acids of mature
      betacellulin and a binding defective form of Pseudomonas exotoxin (BTC-TX48 and
      BTC-TX50, respectively), have been produced. BTC-TX50 induced tyrosine
      phosphorylation of both EGFR and HER4, whereas BTC-TX48 induced phosphorylation
      of HER4 but to a much lesser extent EGFR, indicating that the presence of two
      additional amino acid residues, Arg62 and Lys63, contribute to full kinase
      activity. BTC-TX50 was up to 300-fold more active at inhibiting protein synthesis
      than BTC-TX48 on cell lines expressing EGFR, most likely due to the >tenfold
      higher affinity of BTC-TX50. MDA-MB-453 breast carcinoma cells which express HER4
      but not EGFR, were not sensitive to either BTC-TX form. These data indicate that
      despite the ability of BTC-TX to bind and phosphorylate HER4, it was only
      cytotoxic to cells expressing EGFR. The inability of BTC-TX to kill cells was
      likely due to its failure to internalize through HER4.

PMID- 9528864
TI  - Telomerase activity is restored in human cells by ectopic expression of hTERT
      (hEST2), the catalytic subunit of telomerase.
AB  - The expression of telomerase, the enzyme that synthesizes telomeric DNA de novo,
      is suppressed in normal somatic human cells but is reactivated during
      tumorigenesis. This reactivation appears to arrest the normal loss of telomeric
      DNA incurred as human cells divide. Since continual loss of telomeric DNA is
      predicted to eventually limit cell proliferation, activation of telomerase in
      cancer cells may represent an important step in the acquisition of the cell
      immortalization which occurs during tumor progression. The telomerase holoenzyme
      is composed of both RNA and protein subunits. In humans, mRNA expression of hTERT
      (hEST2), the candidate telomerase catalytic subunit gene, appears to parallel the
      levels of telomerase enzyme activity, suggesting that induction of hTERT is
      necessary and perhaps sufficient for expression of telomerase activity in tumor
      cells. To test this model directly, we ectopically expressed an epitope-tagged
      version of hTERT in telomerase-negative cells and show that telomerase activity
      was induced to levels comparable to those seen in immortal telomerase-positive
      cells and that the expressed hTERT protein was physically associated with the
      cellular telomerase activity. We conclude that synthesis of the hTERT telomerase
      subunit represents the rate-limiting determinant of telomerase activity in these
      cells and that this protein, once expressed, becomes part of the functional
      telomerase holoenzyme.

PMID- 9528865
TI  - Stimulation of p85/RING3 kinase in multiple organs after systemic administration
      of mitogens into mice.
AB  - Using an autophosphorylation membrane assay, we examined activation of kinases in
      different organs after intraperitoneal injections of mitogens and cytokines into
      mice. In the multiple organs examined administration of either epidermal growth
      factor (EGF), phorbol 12-myristate 13-acetate (PMA) or interleukin-1beta (IL
      1beta) activated a number of kinases. Most notably among those was a kinase of
      approximately 85 kDa (p85) that was activated by EGF, PMA and IL-1beta in the
      lung, kidney, brain, liver and heart. The size and properties of this enzyme are
      indistinguishable from the RING3 kinase that has a very high activity in
      leukocytes of patients with leukemia. In animals treated with PMA, antibodies
      against RING3 kinase immunoprecipitated PMA-responsive p85 activity from the lung
      and brain suggesting that p85 and RING3 kinases are the same enzymes. Activation
      of p85/RING3 kinase by growth factors in multiple organs might reflect
      involvement of this enzyme in the pathogenesis of leukemias and other
      proliferative diseases.

PMID- 9528866
TI  - MRI: use of the inversion recovery pulse sequence.

PMID- 9528868
TI  - Fast dynamic contrast enhanced MR imaging of cervical carcinoma.
AB  - The first pass phase of contrast material is most important to study
      vascularization and perfusion of tissue and can be studied using dynamic magnetic
      resonance (MR) imaging. The purpose of this prospective study was to evaluate the
      usefulness of pre-contrast vs. post-contrast and fast dynamic MR imaging in the
      pre-operative staging of cervical carcinomas. To assess the normal onset of
      enhancement of the uterus and cervix 15 volunteers underwent dynamic MR imaging.
      Forty-two consecutive patients with invasive cervical cancer underwent pre
      operative evaluation using MR imaging. The results of the MR examinations were
      correlated with clinical (FIGO) staging under anaesthesia (n = 42) and with
      histopathological findings after operation (n = 26). The staging results of pre
      contrast T1-weighted and T2-weighted turbo spin-echo (TSE) MR images, pre
      contrast MR images plus post-contrast enhanced (two dimensional fast low angle
      shot (FLASH 2-D) post contrast), pre-contrast MR images plus post-contrast
      enhanced plus fast dynamic enhanced (single slice turbo fast low angle shot
      (turbo FLASH)) MR images compared to histopathology (n = 26) were 77%, 81% and
      85% respectively. The improvement was statistically not significant. The result
      of MR staging compared to clinical staging (n = 42) with pre-contrast MR images
      was correct in 79% of the cases. Pre-contrast MR images combined with post
      contrast MR images did not significantly improve staging accuracy (83%). Pre
      contrast plus post-contrast plus fast dynamic MR imaging improved staging to 91%.
      However, the improvement was only statistically significant for one reader (P =
      0.01), whereas the improvement of the second reader was not significant (P =
      0.07). The single slice turbo FLASH images showed enhancement of all squamous
      cell carcinomas (n = 32) with an average onset of 5s (range 4-8s) during the
      first 45s of bolus injection of gadolinium. The normal cervix showed enhancement
      with an average of 10s (range 6-14 s). FLASH 2-D post-contrast images showed less
      intense enhancement of the cervical tumours with respect to the parametria and
      other surrounding structures. Fast dynamic MR imaging and to a lesser degree post
      contrast MR imaging showed a higher level of confidence than pre-contrast MR.
      Fast dynamic MRI compared with clinical staging (n = 42) was correct in 91%
      (38/42) and to histopathology in 85% (22/26). Comparison of clinical staging with
      histopathology was 85% (22/26). In conclusion, fast dynamic MR imaging is
      superior to post-contrast and pre-contrast MR imaging and is at least as good as
      clinical staging in the evaluation of cervical carcinoma.

PMID- 9528867
TI  - A randomized trial of spiral CT and ventilation perfusion scintigraphy for the
      diagnosis of pulmonary embolism.
AB  - PURPOSE: To compare spiral computed tomographic pulmonary angiography (SCTA) with
      lung ventilation-perfusion scintigraphy (VQS) as the initial investigation of
      patients with suspected pulmonary embolism (PE). MATERIALS AND METHODS:
      Prospective randomized trial of 78 patients with suspected pulmonary embolism.
      Patients underwent either SCTA or lung VQS as their initial investigation for PE.
      Cross-over between groups meant that 50 patients received both examinations. The
      clinicians' assessment of overall clinical likelihood of PE was also collected.
      RESULTS: (1) It was possible to make a confident diagnosis in a significantly
      larger proportion of patients when SCTA was used as the initial investigation
      (35/39, 90%) compared with using VQS first (21/39, 54% P<0.001). The main
      difference between the two groups was that SCTA demonstrated lesions other than
      pulmonary embolism considered responsible for the patients' symptoms in 13/39
      patients (33%) randomized to SCTA as the initial investigation and following a
      non-diagnostic VQS in 10/39 patients (25%) randomized to VQS as the initial
      investigation. (2) There was no difference in the prevalence or detection of PE
      in the two groups. SCTA demonstrated pulmonary emboli in 6/39 patients (16%) in
      the SCTA first group and VQS was high probability for PE in 5/39 patients (13%)
      in the VQS first group. SCTA detected PE in a further two patients in the VQS
      first group. CONCLUSION: It is proposed that, where logistically feasible, SCTA
      should replace VQS as the initial investigation for PE in patients with an
      underlying cardio-respiratory disorder.

PMID- 9528869
TI  - Diagnostic accuracy of helical CT for detection of blunt bowel and mesenteric
      injuries.
AB  - OBJECTIVE: To determine the diagnostic accuracy of helical computed tomography
      (CT) in the detection of blunt bowel and mesenteric injury in a clinical setting.
      MATERIALS AND METHODS: We evaluated the helical CT and surgical findings in 31
      patients with blunt abdominal trauma. Nineteen patients had surgically proven
      bowel and/or mesenteric injury, and 12 patients had no bowel or mesenteric injury
      at laparotomy. The CT scans were assessed by three observers in consensus and
      were graded as showing no injury, minor bowel or mesenteric injury (not requiring
      urgent surgery), or major bowel or mesenteric injury (requiring immediate
      surgery). The CT diagnoses were compared with the surgical findings. RESULTS: In
      the 19 cases of surgically proven bowel injury, CT had an accuracy of 84%
      (26/31), specificity 84% (16/19), and negative predictive value 89% (16/18) for
      diagnosis of bowel injury. CT correctly differentiated minor from major bowel
      injuries in eight of 12 cases (75%). For the 13 cases of mesenteric injury, the
      accuracy of CT diagnosis was 77% (24/31), specificity 67% (12/18), and negative
      predictive value 93% (12/13) for diagnosis of mesenteric injury. The CT findings
      allowed correct differentiation of minor from major mesenteric injuries in seven
      of 13 cases (54%). CONCLUSION: Helical CT is moderately accurate and has a high
      negative predictive value in detecting bowel and mesenteric injuries after blunt
      trauma. Helical CT is not highly accurate in predicting the severity of injury or
      need for urgent surgery.

PMID- 9528870
TI  - Multiplanar reformatting and three-dimensional reconstruction: for pre-operative
      assessment of the thoracic aorta by computed tomography.
AB  - INTRODUCTION: Conventional CT demonstrates pathology of the thoracic aorta. This
      study aimed to evaluate the additional contributions to surgical planning of
      multiplanar reformatting, maximum intensity projections and three-dimensional (3
      D) reconstruction. DESIGN: Retrospective. SUBJECT AND METHODOLOGY: Fifty-three
      patients with newly diagnosed pathology of the thoracic aorta were scanned over a
      15-month period; 25 scans were spiral acquisitions. Scans were acquired during
      and following rapid injection of 100 ml of intravenous iopromide. The
      reconstructed data was displayed as axial images, oblique or other multiplanar
      reformats and shaded surface display 3-D reconstructions. Two radiologists and
      two surgeons reviewed the images. The axial images were assessed initially,
      subsequently the reformats and 3-D reconstructed views were examined looking
      particularly for additional information that might add to the surgical
      management. RESULTS: Pathologies encountered were aortic dissection (21 patients,
      including two with Marfan's syndrome), saccular aneurysms (eight), fusiform
      aneurysms (16), aortic root and ascending aortic dilatation (seven) and
      coarctation (one). The relationship of aneurysms and dissections to major vessels
      are better shown with 3-D reconstruction or oblique reformats. Morphology of
      saccular aneurysms, particularly the neck, is well shown with 3-D reconstruction.
      Coarctation was best demonstrated by oblique reformats. There was little
      additional information from 3-D reconstruction or reformats in assessment of type
      A dissection. Improved spatial orientation by visualization in varying
      projections was helpful for surgical planning in certain cases of type B
      dissection, fusiform aneurysms and aortic root and ascending aortic root
      dilatation. Spiral acquisitions have the advantage of speed and hence a greater
      anatomical coverage for a single breath-hold. CONCLUSION: Oblique reformats and 3
      D reconstruction, although using identical data as the axial images, in specific
      cases were felt to aid surgical assessment of aneurysms and dissections, thus
      assisting pre-operative planning.

PMID- 9528871
TI  - Computed tomography compared with small bowel enema in clinically equivocal
      intestinal obstruction.
AB  - OBJECTIVE: To compare the findings in computed tomography (CT) and small bowel
      enema (SBE) in clinically equivocal small bowel obstruction in order to identify
      the reasons for the limitation of CT evaluation. SUBJECT AND METHOD: Over a
      period of 5 years, 49 patients who had both CT and SBE within a period of 1 week
      were analysed. The findings at SBE were categorized into partial low-grade,
      partial high-grade and complete obstruction and compared with the CT findings. A
      critical analysis of the CT false-negative cases was made. The predictive values
      for the determination of the presence of obstruction in CT were also obtained.
      RESULTS: Forty-three out of the 49 patients had proven intestinal obstruction. CT
      correctly identified 34 cases including 19 of 20 with partial high-grade
      obstruction, two with complete obstruction and 13 out of 21 cases of partial low
      grade obstruction. Among those cases with low-grade obstruction cases with
      complex or long segment narrowing or with masses were correctly identified while
      six patients with short stenotic segment due to various causes were not. CT also
      had two false-positive findings of obstruction in patients with mesenteric
      infarction. SBE had neither false positive nor false negative. The sensitivity,
      specificity, positive predictive value and negative predictive values for CT were
      83%, 67%, 94% and 36%, respectively. Abrupt transition from dilated to collapsed
      loops in CT were caused by various intraluminal lesions apart from adhesions. CT
      was superior to SBE in showing extraluminal masses, revealing abscesses,
      tuberculous lesions and malignancy anterior adhesions as well as features of
      strangulation. CONCLUSION: Apart from degree of obstruction and the presence of
      masses, the length of the stenotic part also affected CT detection. Abrupt change
      from dilated to collapsed segment could be due to various transmural and
      intraluminal lesions although adhesions was the commonest lesion. While SBE is
      more accurate in identifying the presence and location of obstruction, CT is
      superior for detection of the cause of small bowel obstruction and also for the
      presence of strangulation. In places where CT is more widely used for intestinal
      obstruction, SBE evaluation could be prudently considered in CT negative cases of
      clinically equivocal intestinal obstruction.

PMID- 9528872
TI  - The role of ultrasound and oesophagography in the management of acute suppurative
      thyroiditis in children associated with congenital pyriform fossa sinus.
AB  - The thyroid is remarkably resistant to infection. Hence, when an infection does
      occur, the presence of a pyriform fossa sinus must be considered, particularly if
      it is recurrent and left sided. The aim of this paper is to alert radiologists to
      the existence, clinical presentation, and ultrasonographic and oesophagographic
      appearances of a pyriform fossa sinus. We present the role of ultrasound and
      oesophagography in five children with pyriform fossa sinus associated with
      suppurative thyroiditis. In four children the abnormality was on the left and on
      the right in one.

PMID- 9528873
TI  - Physical methods of reducing the transmission of nosocomial infections via
      ultrasound and probe.
AB  - Nosocomial infections are posing an increasingly serious problem in the hospital
      setting. With the increasing use of ultrasound in medical diagnosis, there is the
      potential for transmission of nosocomial infections via the ultrasound transducer
      and coupling gel. We evaluated the use of different membranes (three types of
      commercially available household cling film, condom, surgical glove and Opsite)
      applied over the ultrasound probe to determine if these were safe, convenient,
      cost-effective and did not impair the performance parameters of the ultrasound
      probe. None of the membranes impaired the physical scanning parameters using a
      Multi-Purpose Tissue/Cyst Phantom. The cling film was ideal for general use in
      terms of cost and convenience as well as safety. For sterile use the Opsite was
      better overall compared to the surgical glove, though it costs significantly
      more. The condom and surgical glove, though safe, were not very convenient to use
      for scanning.

PMID- 9528874
TI  - A comparison of two or three radiographic views in the diagnosis of skull
      fractures.
AB  - The aim of the study is to determine whether a two rather than a three-view skull
      series is adequate for diagnosis of a skull fracture given a reliable history of
      the site of trauma. The radiographs of 50 patients who were diagnosed and managed
      as having sustained skull fractures were randomly mixed with 200 normal skull
      series and viewed independently by three observers. For all the film series
      viewed (a total of 1500 for the three observers), the diagnostic confidence level
      for two films was 94.4%, and for three films 94.6%. Of a total of 150 skull
      fracture series viewed as two films, 87 (58%) were correctly diagnosed with a
      confidence level of 92.7%. When viewed as three films, 92 (61.3%) were correctly
      diagnosed with a confidence level of 93%. Combined with analysis of false
      positive and false-negative results, no statistical difference could be detected
      between a two or three film skull series. A two-view skull series has no
      statistically deleterious effect on either diagnostic accuracy or confidence of
      interpretation when compared with a three-view series given an accurate clinical
      history.

PMID- 9528875
TI  - Radiography of facial trauma, the lateral view is not required.
AB  - The value of the lateral radiograph in patients who have sustained facial trauma
      has been assessed. Three observers each assessed 200 sets of facial radiographs
      randomly containing either three- (occipito mental, occipito mental 30 and
      lateral) or two-film series (lateral excluded). No additional fractures were
      detected with three films. A sensitivity of 90% and a positive predictive value
      of 0.90 was seen with both three and two-film series. Specificity was 99.3% with
      three films and 97.3% with two films. These differences are not statistically
      significant. We conclude that the lateral film can safely be excluded from the
      initial assessment of patients with facial trauma.

PMID- 9528876
TI  - Spontaneous migration of foreign bodies in the central nervous system.
AB  - The authors present four cases where foreign bodies within the central nervous
      system had spontaneously migrated. Two of these were surgical clips and two were
      bullets. The clips seemed to pass intradurally into the lumbar region with minor
      or no symptoms. Possible explanations for the migration are the circulation of
      CSF and the gravity. A new observation was that an infection may develop at the
      site where the foreign body had been situated before migration. From the clinical
      point of view, the removal of foreign bodies from the intradural space is not
      indicated, if the patient has no connected symptoms.

PMID- 9528877
TI  - Case report: inverted Meckel's diverticulum with associated microcolon.

PMID- 9528878
TI  - Case report: extensive uptake of 99Tc(m)-HMPAO labelled leucocytes in the small
      bowel of a patient with mesenteric ischaemia.

PMID- 9528879
TI  - Case report: tuberculous pulmonary arteritis--an unusual cause of right pulmonary
      artery stenosis.

PMID- 9528880
TI  - Case report: ileobronchial fistula.

PMID- 9528881
TI  - Simethicone coated cellulose as an oral contrast agent for ultrasound of the
      upper abdomen.

PMID- 9528882
TI  - The radiological investigation of suspected lower limb deep vein thrombosis.

PMID- 9528883
TI  - Magnetic resonance cisternography in the localization of CSF fistulae.

PMID- 9528884
TI  - T cell genetics and rheumatoid arthritis (RA)

PMID- 9528885
TI  - Enhanced prostaglandin E2 production by monocytes in atopic dermatitis (AD) is
      not accompanied by enhanced production of IL-6, IL-10 or IL-12.
AB  - AD is associated with a bias of the T helper cells to show increased IL-4 and
      reduced interferon-gamma (IFN-gamma) production. The production of IFN-gamma and
      IL-4 and the development of Th cells into either high IFN-gamma or high IL-4
      producers is strongly influenced by factors produced by antigen-presenting cells
      (APC), like IL-12 and prostaglandin E2 (PGE2). IL-12 selectively enhances IFN
      gamma production and favours the development of IFN-gamma-producing Th cells,
      whereas PGE2 selectively inhibits IFN-gamma production by Th cells. The aim of
      this study was to test whether the increased IL-4/IFN-gamma production ratio by
      Th cells in AD can be explained by an increased PGE2/IL-12 production ratio by
      the APC. Monocytes were used as APC source. PGE2 and IL-12 production by
      lipopolysaccharide (LPS)-stimulated monocytes from 12 AD patients and 12 non
      atopic controls was determined using two complementary experimental systems,
      whole blood cultures and purified monocytes. In addition, we determined IL-6
      production as a measure of monocyte activation, and IL-10 production because IL
      12 production by monocytes is highly influenced by endogenously produced IL-10.
      The monocytes from AD patients showed normal production levels of IL-6 and IL-10,
      a two-fold, but non-significant decrease in IL-12 production, and a significantly
      (three-fold) higher PGE2 production than those from non-atopic controls. Here we
      show for the first time that enhanced PGE2 production by monocytes in AD is not
      accompanied by a general rise in cytokine production. We conclude that AD is
      indeed associated with an increased PGE2/IL-12 production ratio by monocytes.

PMID- 9528886
TI  - Detection of complement C3 and factor B gene expression in normal colorectal
      mucosa, adenomas and carcinomas.
AB  - Local secretion of complement components in the human intestine has been
      previously reported. However, the cellular source has not been identified. In
      this study, we demonstrate complement C3 and factor B mRNA expression in the
      normal colonic mucosa by in situ hybridization analysis. C3 and factor B genes
      were found to be expressed at high levels in the epithelial cells of the lower
      parts of the crypts in colonic mucosa, and this expression decreased gradually
      from the crypt base to the luminal surface. At the upper crypt and the luminal
      surface, these genes almost disappeared. C3 and factor B genes were expressed in
      all crypts at the same level. Furthermore, C3 and factor B gene expression was
      also identified in adenomas and carcinomas. In these neoplastic tissues, C3 and
      factor B genes were expressed uniformly, and the polarized distribution observed
      in the normal crypts was not detected. It is likely that complement components
      are locally synthesized in the intestine, and that these complement components
      may actively participate in normal immune and inflammatory responses over the
      enormous surface area of the intestinal mucosa.

PMID- 9528887
TI  - A blockade of complement activation prevents rapid intestinal ischaemia
      reperfusion injury by modulating mucosal mast cell degranulation in rats.
AB  - We attempted to define the putative role of complement activation in association
      with mucosal mast cell (MMC) degranulation in the pathogenesis of rapid
      intestinal ischaemia-reperfusion (I/R) injury. We prepared complement activity
      depleted rats by the administration of the anti-complement agent K-76COOH and the
      serine-protease inhibitor FUT-175. Autoperfused segments of the jejunum were
      exposed to 60 min of ischaemia, followed by reperfusion for various time periods,
      and the epithelial permeability was assessed by the 51Cr-EDTA clearance rate. The
      number of MMC was immunohistochemically assessed. In control rats, the maximal
      increase in mucosal permeability was achieved by 30-45 min of reperfusion. This
      increase was significantly attenuated by the administration of either K-76COONa
      alone or in combination with FUT-175. In contrast, the administration of
      carboxypeptidase inhibitor (CPI), which prevents the inactivation of complement
      derived anaphylatoxins such as C5a, significantly enhanced the increase in I/R
      induced mucosal permeability. These findings were confirmed morphologically by
      light microscopy and scanning electron microscopy. In addition, the I/R-induced
      mucosal injury was accompanied by a marked decrease in the number of MMC, and
      administration of K-76COOH significantly inhibited this change. These results
      indicate that complement activation and the generation of complement-derived
      anaphylatoxins are key events in I/R-induced mucosal injury. It is likely that
      intestinal I/R-induced mucosal injury may be partially mediated by MMC activation
      associated with the complement activation.

PMID- 9528888
TI  - IgG anti-endothelial cell antibodies (AECA) in type I diabetes mellitus;
      induction of adhesion molecule expression in cultured endothelial cells.
AB  - AECA were detected in 25 of 71 patients with type 1 diabetes mellitus and in two
      of 33 healthy subjects. Patients with diabetes of < 1 year duration and those
      with long-standing disease had the highest levels of these antibodies. Inhibition
      studies suggest that at least part of the AECA reactivity is due to cross
      reactive anti-ssDNA antibodies. AECA-positive sera were able to increase
      intercellular adhesion molecule-1 (ICAM-1) and E-selectin on human umbilical vein
      endothelial cells (HUVEC). Increased binding of polymorphonuclear (PMN) cells was
      also found to accompany raised E-selectin expression. Soluble ICAM-1 and E
      selectin were also found to be increased in the sera of AECA-positive patients.
      An effect of AECA on endothelial cell function is suggested in diabetes mellitus.

PMID- 9528889
TI  - Heterogeneity in the occurrence of a subset of autoantibodies to glutamic acid
      decarboxylase in autoimmune polyendocrine patients with islet cell antibodies.
AB  - Glutamic acid decarboxylase-65 (GAD-65) is a major target for autoantibodies and
      autoreactive T cells in patients with insulin-dependent diabetes mellitus (IDDM).
      Autoantibodies to GAD are also found in patients with stiff man syndrome (SMS) or
      polyendocrine autoimmunity (PE). The epitope specificities of autoantibodies to
      GAD in IDDM and SMS have been well documented, but the locations of autoantibody
      epitopes of GAD in PE patients have not been mapped. Thus, the properties of anti
      GAD antibodies in PE patients (with or without diabetes) were investigated. The
      ability of PE serum antibodies to inhibit the binding of the mouse monoclonal
      antibody, GAD-6, to native GAD in ELISA was determined. For PE patients without
      diabetes, levels of inhibition of GAD-6 binding ranged from 0% to almost 70% and
      were unrelated to the level of binding of serum antibodies to GAD (P = 0.351) or
      to the functional affinities of these antibodies. This suggests differences in
      the epitope specificities of anti-GAD antibodies in different patients. Levels of
      inhibition were also unrelated to clinical condition. SMS antibodies showed
      similar levels of inhibition of GAD-6 binding. Similar analysis was applied to PE
      patients with diabetes and levels of inhibition of GAD-6 binding to GAD were
      determined. These ranged from 0% to 80%, and levels of inhibition were similar in
      samples taken before or after diabetes onset. There was no significant difference
      between anti-GAD antibodies from PE patients with or without diabetes in the
      range of abilities to inhibit GAD-6 binding to GAD, although the highest levels
      of inhibition were given by sera from non-diabetic patients. This raises the
      possibility of differential expression of subsets of anti-GAD antibodies in
      progressive versus slow or non-progressive anti-islet autoimmune responses. Serum
      antibodies of PE and SMS patients did not inhibit the binding of antibodies
      specific for the extreme C-terminus of GAD, indicating that this is not the site
      of the epitopes for the patients' antibodies or for GAD-6.

PMID- 9528890
TI  - Nasal tolerance in experimental autoimmune myasthenia gravis (EAMG): induction of
      protective tolerance in primed animals.
AB  - Nasal administration of microg doses of acetylcholine receptor (AChR) is
      effective in preventing the development of B cell-mediated EAMG in the Lewis rat,
      a model for human MG. In order to investigate whether nasal administration of
      AChR modulates ongoing EAMG, Lewis rats were treated nasally with AChR 2 weeks
      after immunization with AChR and Freund's complete adjuvant. Ten-fold higher
      amounts of AChR given nasally (600 microg/rat) were required to ameliorate the
      manifestations of EAMG compared with the amounts necessary for prevention of
      EAMG. In lymph node cells from rats receiving 600 microg/rat of AChR, AChR
      induced proliferation and interferon-gamma (IFN-gamma) secretion were reduced
      compared with control EAMG rats receiving PBS only. The anti-AChR antibodies in
      rats treated nasally with 600 microg/rat of AChR had lower affinity, reduced
      proportion of IgG2b and reduced capacity to induce AChR degradation. Numbers of
      AChR-reactive IFN-gamma and tumour necrosis factor-alpha (TNF-alpha) mRNA
      expressing lymph node cells from rats treated nasally with 600 microg/rat of AChR
      were suppressed, while IL-4, IL-10 and transforming growth factor-beta (TGF-beta)
      mRNA-expressing cells were not affected. Collectively, these data indicate that
      nasal administration of AChR in ongoing EAMG induced selective suppression of Th1
      functions, i.e. IFN-gamma and IgG2b production, but no influence on Th2 cell
      functions. The impaired Th1 functions may result in the production of less
      myasthenic anti-AChR antibodies and contribute to the amelioration of EAMG
      severity in rats treated with AChR 600 microg/rat by the nasal route.

PMID- 9528891
TI  - Essential pathogenic role for endogenous interferon-gamma (IFN-gamma) during
      disease onset phase of murine experimental autoimmune orchitis. I. In vivo
      studies.
AB  - We previously found that immunization of CH3/He male mice with syngeneic
      testicular germ cells (TGC) without the aid of any adjuvants was sufficient to
      induce DTH to TGC and experimental autoimmune orchitis (EAO). To evaluate the
      role of endogenous IFN-gamma in this model, C3H/He mice immunized subcutaneously
      with TGC on days 0 and 14 received a single injection of anti-murine IFN-gamma
      MoAb on day 15, 20 or 25. On day 45, DTH to TGC was tested, testis specimens were
      collected for histological examination, and blood samples collected for IFN-gamma
      measurement. The results showed that whilst MoAb treatment on day 15 or 25 did
      not influence DTH responses, EAO development, and appearance of IFN-gamma in the
      circulation, treatment on day 20 significantly suppressed all of them. Thus, a
      single injection with anti-IFN-gamma MoAb may successfully down-regulate
      testicular autoimmunity, provided that the treatment is given at an optimal time
      point during disease development.

PMID- 9528892
TI  - B cell-deficient mice do not develop type II collagen-induced arthritis (CIA).
AB  - To investigate the role of B cells in the development of CIA, a model for
      rheumatoid arthritis, we investigated susceptibility to CIA in mice lacking B
      cells due to the deletion of the IgM heavy chain gene (muMT). The muMT deletion
      was backcrossed into two different CIA-susceptible strains, B10.Q and B10.RIII.
      Two different variants of the CIA model are inducible in these strains: in B10.Q
      with rat type II collagen (CII) and in B10.RIII with bovine CII. Homozygous
      deletion of the IgM gene led to the absence of B cells and dramatically reduced
      immunoglobulin levels compared with wild-type mice. The deletion of IgM totally
      abrogated development of CIA in both strains, although the anti-CII T cell
      response did not differ between the muMT and wild-type controls. We conclude that
      B cells play a crucial role in the development of CIA.

PMID- 9528893
TI  - A 75-kD autoantigen recognized by sera from patients with X-linked autoimmune
      enteropathy associated with nephropathy.
AB  - Autoimmune enteropathy (AIE) is a rare disorder characterized by intractable
      diarrhoea and antienterocyte autoantibody. In this study, we detected a 75-kD
      autoantigen which distributed through the whole intestine and the kidney, as
      assessed by Western blot analysis using sera from two unrelated cases of AIE
      associated with nephropathy. Our results suggest that the detection of the
      autoantibody against the 75-kD antigen has a diagnostic value in AIE and that the
      autoimmune reaction against the 75-kD antigen may be implicated in the
      development of intestinal and renal tissue damage in this rare disorder.

PMID- 9528894
TI  - Serum levels of soluble CD30 are increased in ulcerative colitis (UC) but not in
      Crohn's disease (CD).
AB  - Imbalance in Th1 and Th2 subsets and their derived cytokines seems to be involved
      in the immune abnormalities underlying UC and CD. CD30 is a member of the tumour
      necrosis factor/nerve growth receptor superfamily expressed on T cells producing
      Th2 cytokines and released as a soluble form. In this study high levels of
      soluble CD30 were found in sera of UC patients independently of disease activity.
      Furthermore, increased titres of soluble CD30 molecule were shown, in the same
      patients, by mitogen-stimulated cultures of peripheral blood mononuclear cells.
      Our data seem to indicate that an activation of Th2 immune response is involved
      in the pathogenesis of UC, but not of CD. Furthermore, this finding indicates
      that serum soluble CD30 measurement may be helpful for differentiating these two
      forms of inflammatory bowel disease.

PMID- 9528895
TI  - Circulating T lymphocyte subsets in coeliac disease (CoD) patients and healthy
      family members.
AB  - Increased proportions of circulating antigen-primed CD45RO+ TCR gammadelta cells
      have been found in untreated CoD patients. As certain immunological features are
      now found in both CoD and healthy persons carrying the HLA DQ2 heterodimer, we
      sought to establish whether healthy members of the families of CoD patients who
      are positive for HLA DQ2 and also have increased densities of TCR gammadelta
      intraepithelial lymphocytes (IEL) in their small bowel mucosa have elevated
      levels of circulating TCR gammadelta memory cells. Peripheral blood T cells were
      analysed by flow cytometry in 22 patients with CoD and 16 healthy family members.
      Untreated CoD patients had higher percentages of circulating CD45RO+ TCR
      gammadelta cells and CD45RO+ Vdelta1+ cells than healthy family members. On the
      other hand, the amount of circulating Vdelta1+ lymphocytes was lower in patients
      with CoD compared with healthy family members. In contrast, no differences were
      found between HLA DQ2+ and HLA DQ2- healthy family members in respect of
      circulating TCR gammadelta cell subsets. The change in circulating TCR gammadelta
      cell subsets found in patients with CoD is thus a consequence of an ongoing
      immunological process which diminishes on a gluten-free diet rather than a
      phenomenon directly caused by DQ2. These changes in peripheral blood are not
      found in healthy individuals who have the same HLA alleles DQA1*0501 and
      DQB1*0201 encoding the HLA DQ2 and who also have increased densities of TCR
      gammadelta IEL in their otherwise normal jejunal mucosa.

PMID- 9528896
TI  - Anti-mitochondrial antibodies in patients with dilated cardiomyopathy (anti-M7)
      are directed against flavoenzymes with covalently bound FAD.
AB  - Anti-mitochondrial antibodies (anti-M7) in sera from patients with dilated
      cardiomyopathy and myocarditis recognize, besides mitochondrial antigens,
      bacterial sarcosine dehydrogenase. The common target antigen was identified as
      the covalently bound FAD of mitochondrial and bacterial flavoenzymes. Thus, anti
      M7-positive serum reacted on Western blots exclusively with covalently
      flavinylated enzymes. The antigenic specificity of anti-M7 sera was reproduced by
      an antiserum raised in rabbits with 6-hydroxy-D-nicotine oxidase. The heart
      mitochondrial membrane antigen recognized by anti-M7 serum was identified as the
      flavoprotein subunit of succinate dehydrogenase, the antigens in rat liver
      mitochondrial matrix as the flavoenzymes dimethylglycine dehydrogenase and
      sarcosine dehydrogenase. Anti-M7 serum contained a specific anti-flavoenzyme
      antibody fraction. Nanomolar concentrations of FAD and riboflavin inhibited the
      immune reaction on Western blots and in ELISA, and incubation with FAD-agarose
      depleted the anti-M7 activity of the serum. N-terminally deleted dimethylglycine
      dehydrogenase proteins were only immunoprecipitated by anti-M7 sera when the FAD
      was covalently incorporated. An affinity constant (KD) of 10(-8) M was
      established for the anti-flavoenzyme antibodies by competitive ELISA. Of patients
      with cardiomyopathy and myocarditis, 36% and 25%, respectively, were anti
      flavoenzyme-positive by Western blot and ELISA, but only two of 15 patients with
      other heart diseases and none of 50 healthy controls.

PMID- 9528897
TI  - The frequency and avidity of committed cytotoxic T lymphocytes (cCTL) for donor
      HLA class I and class II antigens and their relation with graft vascular disease.
AB  - Cellular immune processes may trigger the development of graft vascular disease
      (GVD). CD4 and CD8 cytotoxic T lymphocytes that infiltrate the allograft could
      play a role in the development of GVD. We studied the presence of in vivo primed
      or committed CTL (cCTL) and their avidity for donor HLA class I and class II
      antigens in graft-infiltrating lymphocyte cultures propagated from endomyocardial
      biopsies derived from patients with and without signs of GVD. The fraction of
      cCTL with high avidity for HLA class I or class II antigens was estimated by the
      addition of anti-CD8 or anti-CD4 MoAbs to the cytotoxic phase of the limiting
      dilution analysis. In the first year after transplantation no difference in the
      frequency of donor-specific class I cCTL between patients with and without GVD
      was found. Addition of anti-CD8 MoAb revealed that most cultures predominantly
      consisted of cCTL with low avidity for donor HLA class I antigens, irrespective
      of the development of GVD at 1 year after transplantation. However, in patients
      who did not develop GVD, the frequency of cCTL with donor HLA class II
      specificity was significantly higher than in patients who did develop GVD. The
      avidity for donor HLA class II antigens was comparable in both groups. A high
      frequency of donor-specific cCTL for HLA class II antigens seems to be a
      protective factor against the development of GVD. These cCTL might be cytotoxic
      for cells involved in GVD development, e.g. activated endothelium and smooth
      muscle cells of donor origin.

PMID- 9528898
TI  - Modifications of general parameters of immune activation in the sera of Sicilian
      patients with Boutonneuse fever.
AB  - The serum levels of beta2-microglobulin (beta2-M), soluble HLA class I antigen
      (sHLA-I), soluble CD4 (sCD4) and CD8 (sCD8) were studied in 98 Sicilian patients
      with Boutonneuse fever (BF). In different stages of infection all markers were
      significantly increased in sera from Sicilian patients with acute BF compared
      with healthy controls. sCD8 and sHLA-I reached the peak in the second week after
      the onset of symptoms, whereas sCD4 and beta2-M reached the peak in the first
      week. Afterwards sCD8 decreased to the levels of controls within the third week,
      the other parameters decreased later and were unmodified until the third week of
      infection. Significant correlations were found between sCD4 and sCD8 and the sIL
      2R, as well as between serum levels of beta2-M and sCD8. The reduction of CD3+
      and CD4+ and the increase of CD8+ T cells in the blood indicate that these cells
      are involved in the response to rickettsia, and their activation might be in part
      responsible for the release of sCD4 and sCD8. Our data suggest that these soluble
      markers, indexes of immune activation of T cells both in the circulation and the
      affected tissues, may be used in monitoring BF evolution.

PMID- 9528899
TI  - Cytomegalovirus (CMV) infection in AIDS patients is associated with a CD3
      receptor-mediated T cell hyporesponsiveness.
AB  - HIV+ individuals with human CMV (HCMV) reactivation have a CD3 receptor-mediated
      T cell hyporesponsiveness when compared with CD4-matched HIV+ and HCMV- control
      groups. The impairment of proliferation was not reversed by exogenous IL-2. A
      typical increase in NFkappaB expression was observed following cross-linking of
      the CD3 receptor, but did not lead to increased CD25 cell surface expression or
      cell proliferation. The HCMV-induced non-responsiveness was not observed when
      cells were stimulated with phorbol esters. Lymphocytes cultured with media
      collected from cell cultures infected with HCMV showed a dose-dependent
      inhibition in the total T cell population even though cells staining dually for
      CD8/57 increased in number. The altered growth factor requirements of CD8/57+
      cells may therefore account for their presence in AIDS and patients following
      bone marrow transplantation.

PMID- 9528900
TI  - The Italian quality control study for evaluation of CD4 cells in centres involved
      in the treatment of HIV-1 patients. Italian CD4 Quality Control Group.
AB  - We report on the experience of establishing a national network for a quality
      control programme in evaluating CD4 cell counts in most Italian centres involved
      in the care of patients with HIV disease. The 68 centres were divided according
      to their geographical location into eight groups, and twice a year (tests A and
      B) they received three coded whole blood samples (two were replicates of the same
      sample) obtained from two informed HIV+ patients, one with CD4 counts/mm3
      expected to be < 200 and one with values > 300. The medians of the determinations
      performed by the labs involved in each of the eight areas were taken as the
      'true' values for each sample. Unsatisfactory performances for percentage of CD4
      cells were identified as a CD4 analysis with residual values > or = +/- 5% and
      with deviates > or = +/- 2. For absolute numbers of CD4 cells, an unsatisfactory
      performance was defined as CD4 counts with residual > +/- 100 CD4 cells/mm3 and
      with deviates > or = +/- 2. The residual value is the CD4 value reported by each
      lab minus the median value. The deviate is the residual divided by the modified
      interquartile range (IQR x 0.75). Most of the centres provided reliable results.
      However, some labs failed to provide satisfactory results for percentages (6.25%
      of the tested labs for test A and 6.17% for test B) or absolute numbers (16.25%
      test A and 12.34% test B). Only 3.7% of the labs gave unsatisfactory results in
      both tests. Four of the unsatisfactory results from the two tests gave an error
      in absolute numbers > +/- 200 CD4 cells/mm3. Our data suggest that most Italian
      labs provide reliable results in evaluating the numbers of CD4 cells in HIV-1+
      samples, but the importance of running a quality control programme is highlighted
      by our experience with those centres which provide unsatisfactory data which may
      lead to incorrect classification of the patients or assessment of treatment.

PMID- 9528901
TI  - Cellular immunity in recurrent vulvovaginal candidiasis.
AB  - Impaired T cell function has been reported to predispose women to recurrent
      vulvovaginal candidiasis, but conflicting results have been noted in the
      literature. Most clinical episodes occur in the late luteal phase, suggesting
      hormonal influence on host resistance. The present study assesses the cellular
      immune responses of 28 women with recurrent vaginal candidiasis (patients) and 25
      control women (controls), noting results in relation to whether the women were in
      the follicular or luteal phase of the menstrual cycle at the time of sampling.
      Candida-stimulated peripheral blood lymphocyte proliferation was significantly
      reduced in patients compared with controls. Interferon-gamma (IFN-gamma)
      production in response to both Candida and purified protein derivative (PPD)
      stimulation was significantly lower in patients compared with controls. Skin test
      responses were comparable in both groups. A significant reduction in Candida
      stimulated IFN-gamma production was seen in patients but not controls in the
      follicular phase compared with those in the luteal phase. There was also a trend
      towards lower proliferation in response to Candida in patients but not controls
      in the follicular phase compared with patients in the luteal phase. These results
      suggest that there is a partial T cell dysregulation in recurrent vaginal
      candidiasis which may be exacerbated by the hormonal balance present during the
      follicular phase, correlating with the risk of clinical infection.

PMID- 9528902
TI  - A tumor necrosis factor-alpha (TNF-alpha) promoter polymorphism is associated
      with chronic hepatitis B infection.
AB  - Cytokines such as TNF-alpha and interferon gamma (IFN-gamma) are important for
      the elimination of infected hepatocytes during acute hepatitis B virus (HBV)
      infection. Two G versus A transitions in the TNF-alpha promoter region at
      positions -308 and -238 possibly influence TNF-alpha expression. We investigated
      these TNF-alpha polymorphisms in 71 patients with chronic HBV infection, in 32
      subjects that had spontaneously recovered from acute HBV infection, and in 99
      healthy controls. The -238 A promoter variant was present in 18 (25%) of 71
      patients with chronic HBV infection compared with two (6%) of 32 subjects with
      acute infection (P<0.04), and seven (7%) of 99 controls (P<0.003). By contrast,
      the prevalence of the variant at position -308 was similar in all investigated
      groups. The observed differences could not be explained by linkage disequilibrium
      to HLA-B or -DRB1* alleles. These findings suggest an association between the TNF
      alpha promoter polymorphism at position -238 and the development of chronic HBV
      infection. This promoter variant appears to be linked to defective viral
      clearance.

PMID- 9528903
TI  - Effective prophylaxis of influenza A virus pneumonia in mice by topical passive
      immunotherapy with polyvalent human immunoglobulins or F(ab')2 fragments.
AB  - The effectiveness of polyvalent plasma-derived human immunoglobulins (IVIG) in
      passive immunotherapy of influenza virus pneumonia was assessed, using the Strain
      Scotland (A/Scotland/74 (H3N2)) adapted to BALB/c mice by repeated lung passages.
      Haemagglutinin antibodies in two batches of IVIG at 10 mg/ml had a titre of 1/16.
      Intravenous injection of 1000-5000 microg of IVIG, 3 h after infection, gave 60
      70% protection, whereas intranasal injection of 25-50 microg protected 90% of
      mice infected with a lethal dose of influenza virus. F(ab')2 fragments were at
      least as protective as intact IVIG, suggesting that complement or Fcgamma
      receptor-bearing cells were not required. Topical passive immunotherapy with IVIG
      or F(ab')2 gave protection up to 8 h after infection, but not at 24 h, suggesting
      that anti-influenza A antibodies in IVIG, delivered locally, are only effective
      at early stages of the infectious process. The potential value of topical
      administration of IVIG or F(ab')2 fragments for influenza A pneumonia prophylaxis
      was further demonstrated by the protective effects of their intranasal
      administration 24 h before challenge.

PMID- 9528904
TI  - Tenidap decreases IL-8 and monocyte chemotactic peptide-1 (MCP-1) mRNA expression
      in the synovial tissue of rabbits with antigen arthritis and in cultured synovial
      cells.
AB  - Since IL-8 and MCP-1 are chemoattractant proteins that participate in the
      recruitment of inflammatory cells into the arthritic joint, we examined the
      effects of tenidap, a new anti-inflammatory drug of the oxindole family, on IL-8
      and MCP-1 expression in the joints of rabbits with acute antigen arthritis. The
      model was induced by injecting 5 mg/ml ovalbumin into the knees of 20
      preimmunized rabbits. Animals were randomized into two groups: treated with
      tenidap (15 mg/kg per 12 h), or untreated. The effect of tenidap treatment was
      evaluated on chemokine production in synovial membranes of rabbits with arthritis
      and in cultured monocytic and synovial cells (SC). By immunoperoxidase staining,
      chemokines were localized in the synovial tissue. Chemokine messenger RNA levels
      in the synovial membranes and in cultured cells were analysed by reverse
      transcription-polymerase chain reaction (RT-PCR). At the end of the study,
      tenidap significantly reduced neutrophil infiltration into the joint cavity (27+/
      4 x 10(6) cells/ml versus 45+/-6 x 10(6) cells/ml in untreated; P<0.05), and
      synovial effusion (134+/-15 microl versus 236+/-19 microl in untreated; P<0.005).
      Untreated rabbits showed synovial membrane up-regulation in mRNA expression of IL
      8 and MCP-1 (11- and seven-fold versus healthy rabbits, respectively) that was
      markedly decreased by tenidap (two- and three-fold versus healthy rabbits,
      respectively). IL-8 and MCP-1 were localized in the synovial tissue in a
      perivascular pattern and areas of the interstitium and lining, mostly coinciding
      with cell infiltration. Tenidap also reduced the accumulation of IL-8 and MCP-1
      proteins. In cultured synovial and monocytic cells, tumour necrosis factor-alpha
      (TNF-alpha) elicited an increase in gene expression of IL-8 (four- and nine-fold,
      respectively) and MCP-1 (nine- and four-fold, respectively) that was
      significantly reversed in both cell types by 10 microM tenidap. These results
      suggest that the beneficial effect of tenidap in acute antigen arthritis could be
      related to the down-regulation in gene expression and synthesis of IL-8 and MCP
      1, two key chemokines involved in the recruitment of inflammatory cells.

PMID- 9528905
TI  - Induction of nitric oxide (NO) synthesis in murine macrophages requires potassium
      channel activity.
AB  - The activation of macrophages for antimicrobial responses is a multistage event
      involving numerous intracellular signalling cascades that makes possible target
      cell destruction by these effector cells. This study examined the effects of
      different potassium channel inhibitors and activators on the NO production of
      murine macrophage-like cell lines P388D.1 and B10-4(S). We found that the
      potassium channel inhibitors tetraethylammonium, 4-aminopyridine, and quinine
      caused dose-dependent reductions in the NO production of macrophages, and that
      the potassium channel activator, minoxidol, caused a dose-dependent enhancement
      of NO production. The inhibition of NO production was due to involvement of
      potassium channels in the priming stage of macrophage activation, since
      pretreatment with the priming agent interferon-gamma partially restored the NO
      response of the macrophages. The results of this study demonstrate a link between
      potassium channel activity and the activation of anitimicrobial functions of
      murine macrophages.

PMID- 9528906
TI  - Correlation of plasma monocyte chemoattractant protein-1 (MCP-1) and monocyte
      inflammatory protein-1alpha (MIP-1alpha) levels with disease activity and
      clinical course of sarcoidosis.
AB  - MCP-1 and MIP-1alpha exhibit chemotactic activity toward macrophages/monocytes
      and induce the production of inflammatory cytokines affecting granuloma
      formation. Up-regulated expression of MCP-1 and MIP-1alpha in the affected organ
      of sarcoidosis has been shown; however, the relationship between their plasma
      levels and the clinical course of this disease has not been determined. In the
      present study we measured plasma MCP-1 and MIP-1alpha levels in 26 patients with
      active sarcoidosis by ELISA in order to assess the state of MCP-1 and MIP-1alpha
      in this disease. Most patients in this study (21/26) had clinical evidence of
      extrathoracic disease in addition to pulmonary involvement. In addition, a high
      proportion of patients (n = 15) showed spontaneous remission of disease, whereas
      five patients showed no spontaneous remission and six patients were treated with
      corticosteroids over the 2-year period of study. At the time of diagnosis, both
      plasma MCP-1 and MIP-1alpha levels in patients with active sarcoidosis were
      significantly higher than in the normal controls. The levels of these cytokines
      in patients with extrathoracic disease were compatible with those in patients
      without extrathoracic disease. A longitudinal evaluation of plasma MCP-1 and MIP
      1alpha levels showed that the changes in both cytokines were closely related to
      the clinical course of sarcoidosis. These results suggest that plasma MCP-1 and
      MIP-1alpha may be useful parameters for monitoring the clinical course of
      sarcoidosis. In addition, plasma MCP-1 and MIP-1alpha may reflect subclinical
      evidence of extrathoracic sarcoidosis and may play a role in initiating monocyte
      migration into the tissue.

PMID- 9528907
TI  - Spontaneous immunoglobulin-producing capacity of cultures from lupus patients and
      normal donors following depletion of cells expressing CD19 or CD38.
AB  - Cells spontaneously secreting IgG or IgM (ISC) are present at a high level in the
      blood of patients with systemic lupus erythematosus (SLE). By use of magnetic
      bead techniques, mononuclear cells from such patients and healthy donors were
      fractionated according to expression of CD19 or CD38 and the cell fractions were
      then cultured in the absence of added mitogen/antigen for 5/6 days. Supernatant
      IgG and IgM were determined and, in addition, in the CD38 experiments ISC were
      enumerated both before and after culture. Much of the immunoglobulin-producing
      capacity of unfractionated cells (UFC) from both donor groups was recovered in
      the CD19- fraction, and no immunoglobulin was produced by CD19+ cells suggesting,
      unexpectedly, that ISC were not expressing CD19. By contrast, CD38 fractionation
      resulted in nearly all ISC passing to the CD38+ fraction which produced levels of
      immunoglobulin approaching 50% that of UFC. On culture of CD38- cells there was a
      build up in the number of IgG and IgM ISC, this being particularly striking in
      the controls with numbers well in excess of those in UFC. Not all these new ISC
      became CD38+, but the maturation process was more efficient in the SLE patients.
      The possibility is discussed that the spontaneous response in the CD38-
      populations is due to removal of CD38+ natural killer (NK) cells. Removal of ISC
      that are present preculture is a helpful initial step in studying ISC generation
      in the disease.

PMID- 9528908
TI  - A critical review of the physiological importance and analysis of sperm movement
      in mammals.
AB  - The identification of human sperm hyperactivated motility has potential
      importance in sperm function tests, as well as in quality control assays and in
      reproductive toxicology investigations. However, relatively little is known about
      this phenomenon and the variety of definitions used for hyperactivation has led
      to a great deal of confusion as to its occurrence and physiological relevance.
      This presentation is a critical review of a number of aspects of hyperactivated
      motility, including its identification and potential role(s) in mammalian
      fertilization. The initial sections of the review consider the mechanisms
      involved in the development and maintenance of mammalian sperm motility, and the
      structural and functional changes in spermatozoa which occur during transport
      through the female reproductive tract. The methods available for the
      quantification of aspects of sperm movement are also discussed, with an
      historical overview of sperm movement analysis.

PMID- 9528909
TI  - Chromosome studies in human sperm nuclei using fluorescence in-situ hybridization
      (FISH).
AB  - The use of chromosome specific DNA probes labelled with fluorochromes and
      especially the combination of several probes has been used to indirectly study
      the chromosome constitution of decondensed sperm nuclei by fluorescence in-situ
      hybridization (FISH), and has allowed to include this test in the protocol of
      study of infertile males. Still, if the test is to be valid, several strict
      conditions must be met, and some specific characteristics have to be taken into
      account. This becomes evident when comparing earlier results with more recent
      ones. The basic technical factors to be taken into account are the methods of
      chromatin decondensation, the number of spermatozoa and of individuals to study,
      the use of internal controls, the scoring criteria, the specificity of the probes
      and the possible existence of polymorphisms that may interfere with the detection
      of fluorescent signals. In the last 7 or 8 years, a large number of papers has
      been published, describing the incidence of aneuploidies in controls, in
      individuals in whom a tendency to non-disjunction was suspected and in infertile
      males. Studies in controls have shown a considerable intra- and inter-individual
      variability in the frequency of aneuploidies, the tendency of some chromosomes to
      undergo non-disjunction (chromosome 21 and the sex chromosomes) and the
      importance of alpha-satellite polymorphisms when using centromere probes. In the
      control population, the frequency of aneuploidy per haploid set has been
      estimated at approximately 6%. The incidence of aneuploidies in sperm nuclei for
      some of the chromosomes more frequently involved in trisomies is considerably
      higher than the incidence of these trisomies established through epidemiological
      data using the global incidence of chromosome abnormalities during the peri
      implantation stage. In infertile males and in males with sex-chromosome
      abnormalities (usually with very low numbers of spermatozoa) the results show an
      increased incidence of sex chromosome aneuploidies and diploid (multi-aneuploid?)
      sperm nuclei. The results could be related to the higher incidence of chromosome
      abnormalities (especially sex-chromosome aneuploidies) observed in children
      conceived by intracytoplasmic sperm injection (ICSI).

PMID- 9528910
TI  - Micromanipulation of gametes and embryos: Cryopreservation of a single human
      spermatozoon within an isolated zona pellucida.

PMID- 9528911
TI  - Erectile dysfunction: an overview.
AB  - Erectile dysfunction is a common (affecting 10-20 million men in the USA) and
      multifactorial disease due to organic and/or psychological factors that strongly
      impairs the quality of life in man. During the past decade many advances in the
      understanding of the pathophysiology of erectile dysfunction have been made and
      new therapeutic strategies have become available. It has been established that an
      insufficient production of nitric oxide by penile nerve terminals and/or vascular
      endothelium may result in an impaired erection or complete impotence. Nowadays,
      intracavernous injection of vasoactive drugs represents a standardized approach
      for the diagnosis, and the treatment of choice, for erectile dysfunction, but is
      not widely accepted by the patients. The possibility of treating erectile
      dysfunction with intraurethral administration of prostaglandin-E1 has recently
      become available in the USA, and is a therapy more acceptable to the patients.
      Other noninvasive medical therapies are undergoing evaluation.

PMID- 9528912
TI  - Doppler ultrasound investigation of uterine and ovarian blood flow in infertility
      and early pregnancy.
AB  - This review describes the current use of Doppler ultrasound to examine blood flow
      in the uterus and ovaries in infertile patients and during early pregnancy. The
      basics of Doppler ultrasound and the different methods of measuring blood flow
      are discussed from the viewpoint of the clinician who may be unfamiliar with
      Doppler physics and terminology. Normal values in the menstrual cycle and the
      relationship of uterine and ovarian blood flow to infertility and to implantation
      following in-vitro fertilization are presented. Normal values for uterine blood
      flow in the first 16 weeks of pregnancy and the effect of sex steroids and
      ovulation induction on their values are described. The possible relationship of
      defective uterine blood flow to recurrent abortion is examined. New areas of
      investigation, such as the effect of standing on blood flow, and the effect of
      drugs are explored. The findings of this review indicate that Doppler blood flow
      studies may provide significant information about possible causes of some
      disorders of infertility and early pregnancy and methods of treatment for the
      same.

PMID- 9528913
TI  - Complications of laparoscopic pelvic surgery: recognition, management and
      prevention.
AB  - Laparoscopic surgery has many advantages but it is not without complications. The
      complexity of the surgery significantly influences the complication rate.
      Laparoscopic surgeons ought to be aware of the possible complications and how
      they could be prevented, recognized without delay, and managed safely and
      efficiently. Important complications include injuries to the vessels, bowel and
      urinary tract. Incisional hernia ought to be reduced by careful closure of the
      fascia whenever a trocar > or =10 mm is used at the extraumbilical site. Gas
      embolism is a rare but potentially life threatening complication. Shoulder pain
      is a minor complication but is exceedingly common; it is less likely to occur if
      as much gas as possible is removed at the end of the operation while the patient
      is still in head down Trendelenburg position. Rare complications include
      pneumothorax, subcutaneous and pre-peritoneal emphysema, cardiac arrhythmia,
      nerve injury and venous thrombosis. Laparoscopic surgeons should also understand
      the principles of electrosurgery and how to avoid complications arising from the
      use of electrical energy including capacitative coupling, direct coupling and
      insulation failure.

PMID- 9528914
TI  - Accumulation of interleukin-1beta and interleukin-6 in amniotic fluid: a sequela
      of labour at term and preterm.
AB  - From the finding of micro-organisms or inflammatory mediators, or both, in
      amniotic fluid (AF), it has been proposed that intrauterine infection is one
      cause of preterm labour (PTL, intact fetal membranes). This theory, however,
      remains unproved, i.e. the accumulation of micro-organisms and inflammatory
      mediators in AF after labour is in progress may be the consequence, not the
      cause, of labour both at term and preterm. This study was conducted to evaluate
      this possibility by a comparison of the concentrations of interleukin (IL)-1beta
      and IL-6 in AFs collected before and during PTL (<34 weeks gestation) with those
      in AFs collected at term (before labour and from the forebag and upper
      compartments of the amniotic sac during labour). The concentrations of IL-1beta
      and IL-6 in AF were also analysed as a function of the duration of labour (term
      or preterm) before fluid collection. In addition, studies were conducted to
      define the source of IL-1beta in AF. A total of 666 AFs were evaluated. IL-1beta
      was not detected (<50 pg/ml) in AFs collected before the onset of labour at any
      stage of gestation (n = 320), including 170 fluids obtained at term. During
      labour, IL-1beta was detected (>50 pg/ml) in 58 out of 106 (54.7%), 17 out of 64
      (26.6%) and 60 out of 176 (34%) of AF samples obtained during PTL, term labour
      (upper compartment) and term labour (forebag) respectively. AF sampling, as well
      as labour and delivery, were completed in <18 h in all term pregnancies. However,
      labour (with cervical dilation) was in progress for >18 h before AF was collected
      in 39 out of 106 (37%) PTL pregnancies. The incidence of IL-1beta-positive
      samples among AFs collected before 18 h of PTL (23 out of 67; 34%) was
      indistinguishable from that in AFs collected during labour at term. However, in
      AFs collected after >18 h PTL, the incidence of IL-1beta-positive samples was 35
      out of 39 (89.7%) The concentrations of IL-1beta (pg/ml; mean +/- SEM) in AFs
      collected during PTL (2680 +/- 730; n = 106) were greater than those in AFs
      collected from the upper compartment and forebag during term labour (436 +/- 244,
      n = 64; and 468 +/- 119, n = 176) respectively; this difference, however, was
      attributable to very high concentrations of IL-1beta in AFs in which PTL was in
      progress for >18 h before AF collection (6021 +/- 1832; n = 39). The
      concentrations of IL-6 in AF were correlated with those of IL-1beta (P < 0.001).
      We conclude that IL-1beta and IL-6 accumulate in AF in a similar proportion of
      pregnancies during the first 18 h of term and preterm labour. Therefore, the
      accumulation of these cytokines in AF cannot be taken as evidence for a role for
      infection in the pathogenesis of PTL.

PMID- 9528915
TI  - Micromanipulation of gametes and embryos: Biopsy of a blastomere from an 8-cell
      human embryo.

PMID- 9528916
TI  - Interstitial adenosine, inosine, and hypoxanthine are increased after
      experimental traumatic brain injury in the rat.
AB  - Adenosine is a putative neuroprotectant in ischemia, but its role after traumatic
      brain injury (TBI) is not clear. Metabolites of adenosine, particularly inosine
      and hypoxanthine, are markers of ischemia and energy failure. Adenosine
      triphosphate (ATP) breakdown early after injury and metabolism of cyclic
      adenosine monophosphate (cAMP) are potential sources of adenosine. Further
      delineation of the magnitude, location, time course, and source of production of
      adenosine after TBI is needed. We measured adenosine, inosine, and hypoxanthine
      in brain interstitial fluid after controlled cortical impact (CCI) in the rat.
      Rats (n = 15) were prepared for TBI induced by CCI. A microdialysis probe was
      placed in the cortex, and samples were collected every 10 min. After 3 h of
      equilibration, the catheter was removed, CCI was performed (4 m/sec, depth 2.5
      mm), and the catheter was replaced. In the shams, the catheter was removed and
      replaced without CCI. The injury group included rats (n = 10) subjected to CCI.
      Within the injury group, the microdialysis probe was placed in the center of the
      eventual contusion (center, n = 5) or in the penumbral region (penumbra, n = 5).
      Purine metabolites were measured using ultraviolet-based high-pressure liquid
      chromatography. Adenosine, inosine, and hypoxanthine were dramatically increased
      after injury (61-fold, 37-fold, and 16-fold, respectively sham, all p < 0.05, two
      way analysis of variance for repeated measures). No changes in cAMP were observed
      (p = 0.62 vs. sham). Adenosine peaked in the first 20 min and returned to near
      baseline 40 min, whereas inosine and hypoxanthine peaked at 30 min and remained
      increased for 40 min after CCI. Interstitial brain adenosine, inosine, and
      hypoxanthine were increased early after CCI in rats in the contusion and
      penumbra. ATP breakdown is a potential source of adenosine in this early period
      while metabolism of cAMP does not appear to play a role. Confirmation of these
      data in humans may suggest new strategies targeting this important metabolic
      pathway.

PMID- 9528917
TI  - 72-kDa heat shock protein and mRNA expression after controlled cortical impact
      injury with hypoxemia in rats.
AB  - As part of the stress response, the 72 kDa heat shock protein (hsp72) is induced
      in neurons after ischemic and traumatic brain injury (TBI). To examine the stress
      response after TBI with secondary insult, we examined the regional and cellular
      expression of hsp72 mRNA and protein after controlled cortical impact (CCI)
      injury with secondary hypoxemia and mild hypotension in rats. Rats were killed at
      6, 8, 24, 72, or 168 h after trauma. Naive and sham-operated rats were used as
      controls. Brains were removed, and in situ hybridization (n = 2/group),
      immunocytochemistry (n = 4/group), and Western blot analysis (n = 3 to 5/group)
      for hsp72 was performed. Hsp72 mRNA was expressed in neurons in the ipsilateral
      cortex, CA3 region of the hippocampus, hilus, and dentate gyrus at 6 h. Hsp72
      mRNA was expressed primarily in the ipsilateral cortex, at 24 h, and by 72 h
      hsp72 mRNA expression returned to near basal levels. Hsp72 protein was seen in
      ipsilateral cortical neurons, hilar neurons, and neurons in the medial aspect of
      the CA3 region of the hippocampus (CA3-c) at 24 h. At 72 h, hsp72
      immunoreactivity was reduced versus 24 h in these same regions, but it was
      increased versus baseline. Western blot analysis confirmed an increase in hsp72
      protein in the ipsilateral cortex. The regional pattern of hsp72 mRNA induction
      in neurons was similar to the pattern of protein expression after CCI, with the
      exceptions that hsp72 mRNA, but not protein, was expressed in the dentate gyrus
      and the lateral aspect of the CA3 region of the hippocampus (CA3-a). The stress
      response, as detected by hsp72 expression, is induced in some neurons in some
      regions that are selectively vulnerable to delayed neuronal death in this model
      of TBI. The failure to translate some proteins including hsp72 may be associated
      with delayed neuronal death in certain hippocampal regions after TBI.

PMID- 9528918
TI  - Neuroprotective effects of MgSO4 and MgCl2 in closed head injury: a comparative
      phosphorus NMR study.
AB  - Previous studies have shown that free magnesium levels decline after traumatic
      brain injury and that magnesium salt administration improves posttraumatic
      outcome. These earlier studies, however, have been limited to models of injury
      that do not produce a significant degree of diffuse axonal injury and have used
      either MgSO4 or MgCl2 as the magnesium salt. The present study compares the
      neuroprotective efficacy of MgSO4 and MgCl2 in a severe model of diffuse axonal
      injury in rats using phosphorus nuclear magnetic resonance spectroscopy and the
      rotarod test to monitor effects on metabolism and neurologic outcome,
      respectively. Both MgSO4 and MgCl2 given as a bolus of 100 micromoles/kg at 30
      min after severe, closed head injury significantly improved brain intracellular
      free magnesium concentration and neurologic outcome. These findings suggest that
      both salts penetrate the blood-brain barrier after brain trauma, enter injured
      tissue, and subsequently improve neurologic outcome.

PMID- 9528919
TI  - Protective effects of aptiganel HCl (Cerestat) following controlled cortical
      impact injury in the rat.
AB  - Recent studies have demonstrated a neuroprotective effect of the noncompetitive N
      methyl-D-aspartate receptor antagonist aptiganel HCl (Cerestat) in focal cerebral
      ischemia. In the present study, we investigated the protective ability of
      aptiganel HCl after controlled cortical impact injury (impact depth = 2 mm;
      impactor velocity = 7 mm/sec) of the left temporoparietal cortex in rats.
      Intravenous aptiganel HCl (2 mg/kg) or a respective volume of vehicle was
      injected 15 min after trauma. Animals were sacrificed 24 h after trauma.
      Contusion volume was measured planimetrically from hematoxylin-eosin-stained
      coronal slices. Hemispheric swelling and water content were determined
      gravimetrically. Thirty minutes before sacrifice, a Codman intracranial pressure
      (ICP) probe was placed in the right hemisphere, and ICP as well as mean arterial
      blood pressure (MABP) and cerebral perfusion pressure (CPP) were monitored.
      Aptiganel HCl reduced contusion volume by 13.6% in treated rats (p < 0.05).
      Hemispheric swelling was also significantly diminished by 31.5% in accordance to
      a decrease in hemispheric water content (controls, 82.78 +/- 0.12%, vs. aptiganel
      HCl, 82.30 +/- 0.18%, p < 0.05). Posttraumatic ICP was not significantly lower in
      the aptiganel HCl treated animals (25.5 +/- 2.4 mm Hg vs. 32.0 +/- 2.7 mm Hg, p =
      0.096). MABP was found to be higher in the treatment group 24 h after injury
      (107.8 +/- 3.6 mm Hg vs. 89.9 +/- 2.4 mm Hg, p < 0.001), resulting in a higher
      CPP (82.6 +/- 4.2 mm Hg vs. 57.2 +/- 4.6 mm Hg, p < 0.05). Taken together,
      aptiganel HCl exerts various beneficial effects following experimental traumatic
      brain injury. It decreases contusion volume and hemispheric swelling as well as
      water content. Thus, this drug appears promising for further clinical trials in
      brain trauma.

PMID- 9528920
TI  - Dissociable long-term cognitive deficits after frontal versus sensorimotor
      cortical contusions.
AB  - Cognitive deficits are the most enduring and disabling sequelae of human
      traumatic brain injury (TBI), but quantifying the magnitude, duration, and
      pattern of cognitive deficits produced by different types of TBI has received
      little emphasis in preclinical animal models. The objective of the present study
      was to use a battery of behavioral tests to determine if different impact sites
      produce different patterns of behavioral deficits and to determine how long
      behavioral deficits can be detected after TBI. Prior to surgery, rats were
      trained to criteria on delayed nonmatching to position, radial arm maze, and
      rotarod tasks. Rats received sham surgery (controls), midline frontal contusions
      (frontal TBI, 2.25 m/sec impact), or unilateral sensorimotor cortex contusions
      (lateral TBI, 3.22 m/sec impact) at 12 months of age and were tested throughout
      the next 12 months. Cognitive deficits were more robust and more enduring than
      sensorimotor deficits for both lateral TBI and frontal TBI groups. Lateral TBI
      rats exhibited transient deficits in the forelimb placing and in the rotarod test
      of motor/ambulatory function, but cognitive deficits were apparent throughout the
      12-month postsurgery period on tests of spatial learning and memory including:
      (1)reacquisition of a working memory version of the radial arm maze 6-7 months
      post-TBI, (2) performance in water maze probe trials 8 months post-TBI, and (3)
      repeated acquisition of the Morris water maze 8 and 11 months post-TBI. Frontal
      TBI rats exhibited a different pattern of deficits, with the most robust deficits
      in tests of attention/orientation such as: (1) the delayed nonmatching to
      position task (even with no delays) 1-11 weeks post-TBI, (2) the repeated
      acquisition version of the water maze--especially on the first "information"
      trial 8 months post-TBI, (3) a test of sensorimotor neglect or inattention 8.5
      months post-TBI, and (4) a DRL20 test of timing and/or sustained attention 11
      months after surgery. These results suggest that long-term behavioral deficits
      can be detected in rodent models of TBI, that cognitive deficits seem to be more
      robust than sensorimotor deficits, and that different TBI impact sites produce
      dissociable patterns of cognitive deficits in rats.

PMID- 9528921
TI  - Adaptation of the fluid percussion injury model to the mouse.
AB  - Fluid percussion injury (FPI) is a well-characterized experimental model of
      traumatic brain injury (TBI) in the rat. Many pathophysiologic consequences and
      mechanisms of recovery after TBI rely on neurochemical pathways that can be
      examined in genetically altered mice. Therefore, FPI applied to mice may be a
      useful experimental tool to investigate TBI at the molecular level. In the
      present study, we establish FPI as a viable model of TBI in the mouse by
      characterizing acute neurological, histopathological, and behavioral changes.
      Right-sided parasagittal FPI or sham treatment was administered in male C57BL/6
      mice. Acute neurological evaluation revealed righting reflexes in the injured
      animals (p < 0.001). Deficits in spatial learning and memory were observed in the
      Morris water maze (MWM) 5 and 6 days after injury. A novel MWM data analysis
      protocol is described. The injured group (n = 18) demonstrated impaired
      performance in the MWM during acquisition (p < 0.05) and probe trials (p < 0.025)
      compared to sham animals (n = 16). At 7 days postinjury, glial fibrillary acidic
      protein immunohistochemistry revealed intense cortical, callosal, and hippocampal
      gliosis. The modified Gallyas silver degeneration stain consistently labeled cell
      bodies and terminals throughout the ipsilateral cortex, axons in the gray matter
      white matter interface above the corpus callosum and within the corpus callosum
      bilaterally, and terminals and fibers in the thalamus bilaterally. Additionally,
      the mouse FPI model described is immediately employable in labs already using the
      FPI rat model with no modifications to a pre-existing FPI apparatus.

PMID- 9528922
TI  - Serum 1alpha,25-dihydroxyvitamin D3 accumulates into the fracture callus during
      rat femoral fracture healing.
AB  - 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) is thought to be an important systemic
      factor in the fracture repair process, but the mechanism of action of 1,25(OH)2D3
      has not been clearly defined. In this study, the role of 1,25(OH)2D3 in the
      fracture repair process was analyzed in a rat closed femoral fracture model. The
      plasma concentration of 1,25(OH)2D3 rapidly decreased on day 3 and continued to
      decrease to 10 days after fracture. We assessed whether this decrease was based
      on the accelerated degradation or retardation of the synthesis rate of
      1,25(OH)2D3, from 25(OH)D3. After radiolabeled 3H-1,25(OH)2D3 or 3H-25(OH)D3 was
      injected i.v. into fractured or control (unfractured) rats, the concentrations of
      25(OH)D3 and 1,25(OH)2D3 metabolites were measured by HPLC. The plasma
      concentrations of these radiolabeled metabolites in fractured group were similar
      to those in control rats early after operation. However, radioactivity in the
      femurs of fractured rats was higher than that of the control group. Furthermore,
      the radioactivity was concentrated in the callus of the fractured group analyzed
      by autoradiography. 1,25(OH)2D3 receptor gene expression was detected early after
      fracture and, additionally, both in the soft and hard callus on days 7 and 13
      after fracture. These results showed that the rapid disappearance of 1,25(OH)2D3
      in the early stages after fracture was not due to either increased degradation or
      decreased synthesis of 1,25(OH)2D3, but rather to increased consumption. Further,
      these results suggest the possibility that plasma 1,25(OH)2D3 becomes localized
      in the callus and may regulate cellular events in the process of fracture
      healing.

PMID- 9528923
TI  - Vasoactive intestinal peptide is an important endocrine regulatory factor of
      fetal rat testicular steroidogenesis.
AB  - This study elaborates our recent preliminary finding that vasoactive intestinal
      peptide (VIP) has a specific stimulatory effect on fetal rat Leydig cells. We
      examined the dose-response relationship for the effect of VIP on cAMP and
      testosterone production by dispersed fetal Leydig cells isolated from rat testes
      on embryonic day (E) 18.5. Further, we used RT-PCR to examine the expression of
      the VIP gene in fetal brain and testes and that of the VIP receptor genes in
      fetal testes and used RIA to measure VIP in testes and plasma during the fetal
      period. VIP stimulated fetal testicular cAMP production at a dose of 10(-9)
      mol/liter, whereas a dose as low as 10(-12) mol/liter stimulated testosterone
      production. This suggests that VIP at low doses may stimulate testosterone
      production using second messenger pathways other than cAMP. RT-PCR analysis could
      not reveal either VIP messenger RNA (mRNA) in fetal tissues or VIP1 receptor mRNA
      in the fetal or newborn testes, whereas VIP2 receptor mRNA was detected in fetal
      testes as early as E15.5. Northern hybridization analysis showed that the level
      of expression of VIP2 receptor mRNA is very low in fetal and neonatal testes and
      increases with age. The testicular VIP content was unmeasurable by our RIA method
      (i.e. <1 fmol/testis), whereas the circulating level of VIP was 82.9 +/- 1.1
      pmol/liter on E17.5 and decreased with advancing fetal age. In conclusion, our
      results suggest that VIP from an extratesticular source, possibly from the
      maternal compartment, may regulate fetal testicular steroidogenesis through type
      2 receptors as early as E15.5. These findings may be of physiological
      significance, because the onset of fetal testicular steroidogenesis occurs at an
      age (E15.5-19.5) before the onset of pituitary LH secretion.

PMID- 9528924
TI  - Regulation of vasopressin synthesis and release by area postrema in rats.
AB  - There is evidence indicating that the area postrema (AP), the most caudal
      circumventricular organ located on the dorsal surface of the medulla, is involved
      in several physiological regulations. In this study, we investigated the role of
      AP in the regulation of arginine vasopressin (AVP) synthesis and release, using
      rats of which the AP was lesioned 6 weeks previously. The level of plasma AVP in
      the AP lesioned (APX) group was significantly lower than in the sham operated
      (Sham) group in the basal state. AVP release induced by either hyperosmolality or
      hypovolemia was significantly attenuated by APX. To clarify the role of AP in AVP
      synthesis in the hypothalamus, we examined the AVP gene expression using in situ
      hybridization. AVP messenger RNA levels in paraventricular (PVN) and supraoptic
      nuclei (SON) in the APX group were significantly lower than in the Sham group in
      the basal state. Moreover, the AVP messenger RNA levels in PVN and SON in the APX
      group were also significantly lower than in the Sham group after water
      deprivation for 3 days. These results suggest that AVP synthesis and release are
      tonically stimulated by AP in the basal state and that AVP synthesis and release
      in stimulated states are also regulated, at least partially, by AP.

PMID- 9528925
TI  - Up-regulation of insulin-like growth factor binding protein-5 is independent of
      muscle cell differentiation, sensitive to rapamycin, but insensitive to
      wortmannin and LY294002.
AB  - Skeletal myoblast differentiation is stimulated by insulin-like growth factors
      (IGFs). The autocrine action of IGFs is mediated through the type-1 IGF receptor
      (IGFR-1) and modulated by IGF binding proteins (IGFBPs) secreted by the cells.
      The mouse C2 myoblast cell line stably transfected with a vector producing IGF-II
      antisense RNA was used to show that specific IGFBP expression changes with the
      state of the cells: high levels of IGFBP-2 messenger RNA (mRNA) were found only
      in proliferating myoblasts, whereas IGFBP-3 mRNA was induced in quiescent cells.
      Secretion of IGFBP5 was strongly stimulated during differentiation. Insulin and
      IGF dose-response experiments showed that up-regulation of IGFBP-5 resulted from
      IGFR-1 activation. Drugs interfering with IGFR-1 signaling and inhibiting
      myoblast differentiation had different effects on IGFBP-5 up-regulation. Two
      phosphatidylinositol 3-kinase (PI 3-kinase) inhibitors, wortmaninn and LY294002
      [2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one], failed to alter IGFBP-5 up
      regulation, which persisted in the absence of differentiation. Rapamycin which
      indirectly prevents activation of the p70 ribosomal protein-S6 kinase (p70S6k),
      suppressed IGFBP-5 induction. Because the PI3-kinase inhibitors block p70S6k,
      neither kinase would be required for IGFR-1-dependent IGFBP-5 induction. In C2
      anti-IGF-II myoblasts, IGFBP-5 induction is therefore rapamycin-sensitive and
      independent of differentiation.

PMID- 9528926
TI  - Growth factor-mediated proliferation and differentiation of insulin-producing INS
      1 and RINm5F cells: identification of betacellulin as a novel beta-cell mitogen.
AB  - It is not clear which growth factors are crucial for the survival, proliferation,
      and differentiation of pancreatic beta-cells. We used the relatively
      differentiated rat insulinoma cell line INS-1 to elucidate this issue.
      Responsiveness of the DNA synthesis of serum-starved cells was studied to a wide
      variety of growth factors. The most potent stimulators were PRL, GH, and
      betacellulin, a member of the epidermal growth factor (EGF) family that has not
      previously been shown to be mitogenic for beta-cells. In addition to these, only
      vascular endothelial growth factor, insulin-like growth factor-1 and -2, had
      significant mitogenic activity, whereas hepatocyte growth factor, nerve growth
      factor-beta, platelet-derived growth factors, basic fibroblast growth factor,
      EGF, transforming growth factor-alpha (TGF-alpha), neu differentiation factor,
      and TGF-beta were inactive. None of these factors affected the insulin content of
      INS-1 cells. In contrast, certain differentiation factors, including
      nicotinamide, sodium butyrate, activin A, and 1,25-dihydroxyvitamin D3 inhibited
      the DNA synthesis and increased the insulin content. Also all-trans-retinoic acid
      had an inhibitory effect on cell DNA synthesis but no effect on insulin content.
      From these findings betacellulin emerges as a novel growth factor for the beta
      cell. Half-maximal stimulation of INS-1 DNA synthesis was obtained with 25 pM
      betacellulin. Interestingly, betacellulin had no effect on RINm5F cells, whereas
      both EGF and TGF-alpha were slightly mitogenic. These effects may possibly be
      explained by differential expression of the erbB receptor tyrosine kinases. In
      RINm5F cells a spectrum of erbB gene expression was detected (EGF receptor/erbB
      1, erbB-2/neu, and erbB-3), whereas INS-1 cells showed only expression of EGF
      receptor. Expression of the erbB-4 gene was undetectable in these cell lines. In
      summary, our results suggest that the INS-1 cell line is a suitable model for the
      study of beta-cell growth and differentiation because the responses to previously
      identified beta-cell mitogens were essentially similar to those reported in
      primary cells. In addition, we have identified betacellulin as a possible
      modulator of beta-cell growth.

PMID- 9528927
TI  - Phosphate transport in pig proximal small intestines during postnatal
      development: lack of modulation by calcitriol.
AB  - The role of calcitriol in the intestinal absorption of inorganic phosphate (Pi)
      during postnatal development was studied in newborn [<1 week postpartum (pp)],
      suckling (3-4 weeks pp), and weaned (>6 weeks pp) control piglets (con) and
      piglets suffering from inherited calcitriol deficiency (def). In addition, a
      number of def piglets were treated with vitamin D3 (def-D3). Regardless of age,
      plasma calcitriol concentrations in def piglets were unphysiologically low (16-21
      pg/ml) and differed significantly from those in respective con animals (60-69
      pg/ml) and vitamin D3-treated def piglets (50-56 pg/ml). However, newborn and
      suckling def piglets had normal Ca (approximately 3.0 mmol/liter) and Pi
      (approximately 2.8 mmol/liter) plasma levels. Def piglets became hypocalcemic
      (1.9 mmol/liter) and hypophosphatemic (1.9 mmol/liter) between 4-6 weeks pp.
      Treatment with vitamin D3 significantly increased plasma Ca (3.2 mmol/liter) and
      Pi (2.7 mmol/liter) levels in weaned def animals. Regardless of calcitriol
      status, net Pi flux rates (active Pi absorption, as determined with the in vitro
      Ussing-chamber technique) from the upper small intestines was maximal at birth
      [170-224 nmol/(cm2 x h)] and decreased by approximately 80% during the first week
      of life before remaining constant [30-50 nmol/(cm2 x h)] during the following
      development. In weaned def piglets, net Pi flux rates were significantly lower by
      about 80% compared with those in con animals. Treatment of def piglets with
      vitamin D3 had no effect in newborn and suckling animals but reconstituted net Pi
      flux rates to normal values at weaning age. Age-dependent and calcitriol-mediated
      changes in net Pi flux rates were paralleled by respective maximum velocity
      values of Na+-dependent Pi uptake across the brush border membrane of the
      enterocytes (newborn piglets, 1.9-2.2 nmol/(mg protein 10 sec); suckling piglets,
      0.4-0.6 nmol/(mg protein x 10 sec); weaned piglets, 0.7, 0.3, and 0.7 nmol/(mg
      protein x 10 sec) in con, def, and def-D3 animals, respectively). These findings
      suggest that the apical Pi uptake represents the major rate-limiting step of the
      overall transepithelial Pi transport. At weaning, Na+/Pi transport across the
      intestinal brush-border membrane is clearly stimulated by calcitriol, but no
      significant effects of age or calcitriol on the Km values (0.5-0.7 mmol/liter)
      were observed. In conclusion, our findings reveal calcitriol-independent
      mechanisms for active intestinal Pi absorption during the neonatal and suckling
      periods. The onset of the classical calcitriol-dependent mechanism for active
      intestinal Pi absorption does not occur until weaning.

PMID- 9528928
TI  - Evidence that melatonin acts in the premammillary hypothalamic area to control
      reproduction in the ewe: presence of binding sites and stimulation of luteinizing
      hormone secretion by in situ microimplant delivery.
AB  - Melatonin transduces the effect of day length on LH secretion by acting on the
      hypothalamus. However, the precise hypothalamic site is unknown. Two studies were
      undertaken to clarify where melatonin acts in the hypothalamus. Using
      autoradiographic methods, the hypothalami of 5 ewes were screened to determine
      whether specific regional densities in melatonin binding existed. A higher
      density of binding was observed in the premammillary area of the hypothalamus
      (PMH) (3- to 5-fold higher than the rest of the hypothalamus). This binding area
      is delimited rostrally by the infundibular recess, caudally by the mammillary
      bodies, dorsally by the fornix, and ventrally by the base of the brain; and it
      encompasses the premammillary and tuberomammillary nuclei. To test the functional
      importance of the identified area, 3 groups of animals received bilateral
      melatonin microimplants: 1) in the PMH (n = 11); 2) in the anterior/mediobasal
      hypothalamus (AH/MBH; n = 8); and 3) sham-operated animals received empty
      microimplants in the PMH (SHAM; n = 6). All ewes were ovariectomized and treated
      s.c. with a 20-mm SILASTIC brand capsule of estradiol and exposed to long days
      (16-h light, 8-h dark). At the end of the 80-day experiment, no animal of the
      SHAM group and only 2 of the 8 ewes of the AH/MBH group displayed a stimulation
      of LH secretion. In contrast, melatonin implanted in the PMH stimulated LH
      secretion in 10 of the 11 ewes on day 44.5 +/- 5.3 (mean +/- SEM). ANOVA revealed
      that the changes in LH secretion were not different between the SHAM and the
      AH/MBH groups but the PMH group differed from the other 2 groups (P < 0.0001).
      This study suggests that the PMH is an important target for melatonin to regulate
      reproductive activity.

PMID- 9528929
TI  - Tissue-specific messenger ribonucleic acid expression of 11beta-hydroxysteroid
      dehydrogenase types 1 and 2 and the glucocorticoid receptor within rat placenta
      suggests exquisite local control of glucocorticoid action.
AB  - Placental 11beta-hydroxysteroid dehydrogenase (11beta-HSD) regulates
      transplacental passage of maternal glucocorticoids to the fetus and is thus a key
      determinant of fetal glucocorticoid levels. It has also been proposed that
      placental 11beta-HSD expression may influence local glucocorticoid actions by
      regulating access of corticosterone to the glucocorticoid receptor (GR) or
      mineralocorticoid receptor (MR). Therefore, the present study used a rat model to
      assess whether the GR or MR are coexpressed with the two forms of 11beta-HSD
      (types 1 and 2) in the placental labyrinth zone, the major site of maternal-fetal
      transfer, and in the basal zone, the primary site of placental hormone synthesis.
      In situ hybridization analysis was used to assess messenger RNA (mRNA) expression
      for the GR, MR, 11beta-HSD-1, and 11beta-HSD-2 in the two placental zones on days
      16, 19 and 22 of pregnancy (term = day 23). Whereas expression of the GR appeared
      relatively unchanged in both zones at these three stages of pregnancy, that of
      11beta-HSD-1 clearly increased in the labyrinth zone but fell in basal zone,
      whereas the opposite pattern of expression was observed for 11beta-HSD-2. MR
      expression was not detected at any stage. The pattern of placental 11beta-HSD-2
      mRNA expression over days 16, 19, and 22 of pregnancy was paralleled by changes
      in 11beta-HSD-2-specific bioactivity, but despite clear expression of 11beta-HSD
      1 mRNA, no bioactivity attributable to this enzyme was measurable in either
      placental zone. To assess the role of fetal adrenal maturation on these changes
      in 11beta-HSD, two experimental models, maternal adrenalectomy and fetectomy,
      were employed. Maternal adrenalectomy on day 13 advanced maturation of the fetal
      adrenal cortex but had no effect on 11beta-HSD-2 bioactivity in either of the
      placental zones at day 19. Placental 11beta-HSD-2 bioactivity on day 22 was also
      unaffected by fetectomy 3 or 6 days earlier. In conclusion, the consistent
      expression of the GR in the two placental zones late in pregnancy suggests that
      concomitant and marked changes in 11beta-HSD-1 and 11beta-HSD-2 expression could
      have a major influence on glucocorticoid action in the placenta at this time.
      Moreover, the changes in 11beta-HSD expression appear to be unrelated to
      development of the fetal adrenal cortex and are likely to reduce the placental
      glucocorticoid barrier near the end of pregnancy.

PMID- 9528930
TI  - Effects of leptin on corticotropin-releasing factor (CRF) synthesis and CRF
      neuron activation in the paraventricular hypothalamic nucleus of obese (ob/ob)
      mice.
AB  - The effects of leptin on the levels of CRF messenger RNA (mRNA) in the
      paraventricular hypothalamic nucleus (PVN), on the activation of the PVN CRF
      cells, and on the plasma levels of corticosterone were investigated in lean (+/?)
      and obese (ob/ob) C57BL/6J male mice. Murine leptin was s.c. infused using
      osmotic minipumps. The treatment period extended to 7 days, and the daily dose of
      leptin delivered was 100 microg/kg. The mice were killed either in a fed state or
      following 24 h of total food deprivation. The starvation paradigm was employed to
      enhance the activity of the hypothalamic-pituitary-adrenal axis in obese mice. In
      situ hybridization histochemistry was performed to determine the PVN levels of
      CRF mRNA and the arcuate nucleus levels of neuropeptide Y mRNA. The activity of
      the PVN CRF cells was estimated from the number of PVN cells colocalizing CRF
      mRNA and the protein Fos. Leptin led to a reduction in body weight gain and fat
      deposition. These effects were seen in both +/? and ob/ob mice and were observed
      to be particularly striking in obese mutants, in which leptin also caused an
      important reduction in food intake. Leptin also was found to affect plasma levels
      of corticosterone. It lowered the high corticosterone levels of obese mutants, an
      effect that appeared more evident in food-deprived than in fed mice. Finally,
      leptin prevented the induction of CRF synthesis in the PVN and the activation of
      the PVN CRF neurons observed in food-deprived ob/ob mice and hindered the
      elevation of arcuate nucleus neuropeptide Y synthesis in ob/ob mice. Together
      these results suggest a role for leptin in the excessive response of the
      hypophysiotropic CRF system of the ob/ob mouse.

PMID- 9528931
TI  - Reduced 11beta-hydroxysteroid dehydrogenase activity in the remaining kidney
      following nephrectomy.
AB  - Intracellular access of steroids to gluco- and mineralocorticoid receptors is
      regulated by reduced 11beta-hydroxysteroid dehydrogenase (OHSD) 1 and 2. These
      enzymes convert active 11beta-OH-steroids into inactive 11-keto-steroids. The
      purpose of the present study was to establish whether the 11beta-OHSD1 and 11beta
      OHSD2 are modulated in the remnant kidney 24 h or 14 days after uninephrectomy
      (UNX) in rats. Overall, 11beta-OHSD activity was analyzed by measuring the ratio
      of the exogenous 11beta-OH-steroid prednisolone to its 11-keto metabolite
      prednisone in vivo in kidney tissue using high performance liquid chromatography.
      To determine which isoenzyme accounts for the changed activity 24 h after UNX,
      the oxidation and reduction attributable to 11beta-OHSD1 and oxidation to 11beta
      OHSD2 were analyzed in total renal extracts and in isolated glomeruli, proximal
      convoluted tubules (PCT), cortical ascending limbs, and cortical convoluted
      tubules (CCT). The messenger RNA content of 11beta-OHSD1 and 11beta-OHSD2 was
      measured by RT-PCR in renal tissues and single segments, using glyceraldehyde-3
      phosphate-dehydrogenase as an internal standard. Protein amounts of 11beta-OHSD1
      and 11beta-OHSD2 were assessed by Western blot. The prednisolone/prednisone ratio
      increased 24 h after UNX in 9 out of 10 animals (P < or = 0.0011), and was
      unchanged 14 days after UNX. 11Beta-OHSD1 oxidation (P < or = 0.032) and
      reduction activity (P < or = 0.002) declined 24 h after UNX in total extracts.
      11Beta-OHSD1 oxidase activity was more than 3 times higher in PCT than in
      glomeruli, cortical ascending limbs, and CCT, and declined by 50% after UNX (P <
      or = 0.001). The reductase activity did not change following UNX in PCT. 11Beta
      OHSD2 activity was 5-15 times higher in CCT than in the other segments, and
      decreased significantly after UNX (P < or = 0.008). UNX did not affect messenger
      RNA and protein levels of both enzymes in total renal extracts. In conclusion,
      11beta-OHSD1 and 11beta-OHSD2 are predominantly expressed in PCT and CCT,
      respectively, and their corresponding oxidative activities decline after UNX.
      Thus, the access of 11beta-glucocorticosteroids to gluco- and mineralocorticoid
      receptors in the remaining kidney is facilitated after UNX.

PMID- 9528932
TI  - Intercellular differences in interleukin 1beta-induced suppression of insulin
      synthesis and stimulation of noninsulin protein synthesis by rat pancreatic beta
      cells.
AB  - The normal pancreatic beta-cell population exhibits intercellular differences in
      its responsiveness to glucose. This cellular heterogeneity allows glucose to
      regulate, in a dose-dependent manner, total rates of insulin synthesis and
      release. It may also predispose to intercellular differences in susceptibility to
      dysregulating agents. The present study examines whether this is the case for
      interleukin 1beta (IL-1beta), which is known to suppress glucose-induced insulin
      synthesis and release. The effects of the cytokine were compared on beta-cell
      subpopulations with, respectively, high and low sensitivity to glucose. These
      subpopulations were separated on the basis of differences in the cellular
      metabolic responsiveness to an intermediate glucose concentration (7.5
      mmol/liter) and then cultured for 20 h at 5 or 20 mmol/liter with or without IL
      1beta. The suppressive action of IL-1beta (0.1 ng/ml) occurred predominantly in
      glucose-activated beta cells, reducing their high rates of insulin synthesis and
      release by more than 80%. Glucose-unresponsive cells became subject to a similar
      inhibition after their activation during culture at 20 mmol/liter glucose. On the
      other hand, IL-1beta induced or enhanced the expression of several noninsulin
      proteins in both subpopulations. The IL-1beta-stimulated expression of inducible
      nitric oxide synthase (iNOS) and heat shock protein 70 was more marked in the
      glucose-responsive subpopulation; that of heme oxygenase and Mn superoxide
      dismutase was comparable in the two subpopulations. Exposure to IL-1beta resulted
      in 10-fold higher medium nitrite levels in both subpopulations; this effect was
      prevented by the iNOS blocker, N(G)-methyl-L-arginine, which also prevented the
      IL-1beta-induced suppression in the glucose-responsive subpopulation. This study
      demonstrates that the cellular heterogeneity in glucose responsiveness
      predisposes to intercellular differences in the IL-1-induced suppression of
      insulin synthesis and release. While the cytokine induces the expression of
      noninsulin proteins such as iNOS in both glucose responsive and unresponsive
      cells, the subsequent nitric oxide production appears to predominantly affect
      glucose-stimulated functions in the glucose-activated cells.

PMID- 9528933
TI  - Chronic effects of a nonpeptide corticotropin-releasing hormone type I receptor
      antagonist on pituitary-adrenal function, body weight, and metabolic regulation.
AB  - CRH, the principal regulator of the hypothalamic-pituitary-adrenal axis and
      modulator of autonomic nervous system activity, also participates in the
      regulation of appetite and energy expenditure. Antalarmin, a pyrrolopyrimidine
      compound, antagonizes CRH type 1 receptor-mediated effects of CRH, including
      pituitary ACTH release, stress behaviors, and acute inflammation. We administered
      antalarmin chronically to evaluate its effects on hypothalamic-pituitary-adrenal
      axis function and metabolic status. Adult male rats were treated twice daily with
      20 mg/kg of i.p. antalarmin or placebo over 11 days. The animals were weighed;
      plasma ACTH, corticosterone, leptin, and blood glucose levels were determined;
      and morphometric analyses were performed to determine adrenal size and structure,
      including sizing, histochemistry, immunohistochemistry, and electron microscopy.
      Leptin messenger RNA expression in peripheral fat was analyzed by Northern blot.
      Antalarmin decreased plasma ACTH (mean +/- SD, 2.62 +/- 0.063 pg/ml) and
      corticosterone concentrations (10.21 +/- 1.80 microg/dl) compared with those in
      vehicle-treated rats [respectively, 5.3 +/- 2.0 (P < 0.05) and 57.02 +/- 8.86 (P
      < 0.01)]. Antalarmin had no significant effect on body weight, plasma leptin, or
      blood glucose concentrations or fat cell leptin messenger RNA levels. The width
      of the adrenal cortex of animals treated with antalarmin was reduced by 31%
      compared with that in controls without atrophy of the gland. On the
      ultrastructural level, adrenocortical cells were in a hypofunctional state
      characterized by reduced vascularization, increased content of lipid droplets,
      and tubulovesicular mitochondria with fewer inner membranes. The apoptotic rate
      was increased in the outer zona fasciculata of animals treated with the
      antagonist (26.6 +/- 3.58%) compared with that in placebo-treated controls (6.8
      +/- 0.91%). We conclude that chronic administration of antalarmin does not affect
      body weight, carbohydrate metabolism, or leptin expression, whereas it reduces
      adrenocortical function mildly, without anatomical, clinical, or biochemical
      evidence of causing adrenal atrophy. These results are promising for future uses
      of such an antagonist in the clinic.

PMID- 9528934
TI  - Proteolysis of insulin-like growth factor binding proteins by a novel 50
      kilodalton metalloproteinase in human pregnancy serum.
AB  - Insulin-like growth factor binding proteins (IGFBP) proteases have been proposed
      to be involved in changes of serum IGFBP pattern during pregnancy. IGFBP-4 and -5
      are degraded specifically by proteases in pregnancy serum in vitro, whereas IGFBP
      3 proteolytic activity was also detected in nonpregnancy serum. To identify and
      characterize IGFBP proteases, human pregnancy serum was fractionated by size
      exclusion chromatography revealing IGFBP-4 protease activities in fractions
      coeluting with proteins of approximately 600-kDa and 50- to 100-kDa molecular
      mass. In both fractions, a predominant 50-kDa gelatinase was found, suggesting
      that parts of the gelatinase activity might aggregate or are complexed with other
      proteins forming a higher molecular complex. Hydroxyapatite chromatography and
      chromatofocusing of the 50- to 100-kDa serum fraction showed that the IGFBP-4
      protease and the 50-kDa gelatinase activity were copurified. When the 50-kDa
      gelatinase-containing band was excised from the polyacrylamide gel, it exhibited
      IGFBP-4 proteolytic activity, resulting in the formation of 17- and 10-kDa
      fragments. [125I] IGFBP substrate zymography combined with fragment blotting
      showed that the 1,10-phenanthroline-sensitive 50-kDa protease activity purified
      by chromatofocusing also cleaved IGFBP-3 and -5. Other proteases detected in
      pregnancy serum fractions with Mr estimates of 79-, 30-, and 22-kDa degraded
      IGFBP-3 and -5 but not IGFBP-4. [125I] IGFBP-5 substrate zymography revealed that
      the 30-kDa IGFBP protease was inhibited by serine protease inhibitors. Whereas
      1,10-phenanthroline inhibited the IGFBP proteolytic activity in the solution
      assay, serine protease inhibitors failed to affect proteolysis, indicating the
      predominant contribution of the metalloproteinase to IGFBP proteolysis. Tissue
      inhibitors of matrix metalloproteinases-1 and -2 revealed weak or no inhibition
      of IGFBP-4 and -5 proteolytic activity, whereas a hydroxamic acid-based
      inhibitor, potentially inhibiting disintegrin metalloproteases, completely
      prevented the proteolysis of IGFBPs. Whereas no specific immunoreactivity of the
      50-kDa protein with antimatrix metalloproteinase-1, -2, -3, -9, or -13 antibodies
      was observed, antidisintegrin domain-specific antibodies bound to the 50-kDa
      gelatinase. These studies provide the first direct biochemical evidence that
      human pregnancy serum contains a 50-kDa IGFBP protease with properties of a
      soluble disintegrin metalloproteinase that appears to be potentially involved in
      regulating IGF bioavailability for placental and fetal growth.

PMID- 9528935
TI  - The cellular actions of interleukin-11 on bone resorption in vitro.
AB  - The pleiotropic cytokine interleukin-11 (IL-11) stimulates osteoclast formation
      in vitro, but it is not known whether it influences other steps in the bone
      resorptive cascade. Using a variety of in vitro model systems for studying bone
      resorption we have investigated the effects of IL-11 on 1) osteoclast formation,
      fusion, migration, and activity; and 2) osteoblast-mediated osteoid degradation.
      The involvement of matrix metalloproteinases (MMPs) and products of arachidonic
      acid metabolism in IL-11-mediated resorption were also assessed. We first
      examined the bone-resorptive effects of IL-11 by assessing 45Ca release from
      neonatal mouse calvarial bones. IL-11 dose-dependently stimulated bone resorption
      with an EC50 of 10(-10) M. The kinetics of IL-11-mediated 45Ca release
      demonstrated that it was without effect for the first 48 h of culture, but by 96
      h, it stimulated 45Ca release to the same level as that produced by 1,25
      dihydroxyvitamin D3 [1,25-(OH)2D3] (a hormone that stimulates osteoclast
      formation and activity). IL-11 also produced a dose-dependent increase in
      osteoblast-mediated type I collagen degradation with a maximum of 58.0 +/- 6.2%
      at 5 x 10(-9) M; this effect of IL-11 was less than that produced by 1,25-(OH)2D3
      (76.5 +/- 7.1%) and was prevented by an inhibitor of MMPs, but not those blocking
      arachidonic acid metabolism. We then tested the effects of IL-11 on isolated
      mouse osteoclasts cultured on ivory slices in the presence and absence of primary
      mouse osteoblasts. IL-11 had no effect on isolated osteoclast activity even in
      coculture with primary osteoblasts. We then examined the effects of IL-11 on the
      formation of osteoclast-like multinucleate cells in mouse bone marrow cultures
      and the resorptive activity of such cultures using ivory as a substrate. IL-11
      dose-dependently increased 1) the number of tartrate-resistant acid phosphatase
      positive osteoclast-like multinucleate cells and 2) the surface area of lacunar
      resorption, although the effects were less than that of 1,25-(OH)2D3. The effect
      of IL-11 on bone marrow lacunar resorption was prevented by a combination of
      inhibitors of 5-lipoxygenase and cyclooxygenase. In 17-day-old metatarsal bones,
      IL-11 prevented the migration of (pre)osteoclasts to future resorption sites,
      whereas their fusion was unaffected. These results provide strong evidence that
      IL-11 stimulates bone resorption by enhancing osteoclast formation and osteoblast
      mediated osteoid degradation rather than stimulating osteoclast migration and
      activity. Our data also suggest that the stimulatory effects of IL-11 involve
      both MMPs and products of arachidonic acid metabolism.

PMID- 9528936
TI  - Chronic treatment with estrogen up-regulates expression of sst2 messenger
      ribonucleic acid (mRNA) but down-regulates expression of sst5 mRNA in rat
      pituitaries.
AB  - We previously showed that 17beta-estradiol (E2) induces the somatostatin (SRIF)
      responsiveness of the rat anterior pituitary, which leads to inhibition of PRL
      secretion through E2-dependent SRIF receptors. To examine receptor subtypes
      regulated by E2, we determined the messenger ribonucleic acid (mRNA) levels of
      all subtypes using a semiquantitative RT-PCR and characterized pituitary membrane
      receptors using subtype-preferential SRIF analogs. Most of the SRIF receptor
      subtype mRNAs were sst5 and sst2A in ovariectomized rat pituitaries
      [sst5/glyceraldehyde 3-phosphate dehydrogenase (GAPDH) = 1.4 x 10(-2),
      sst2A/GAPDH = 0.4 x 10(-2)]. The expression pattern of the subtypes in
      ovariectomized rat pituitaries was similar to that of normal male and female rat
      pituitaries, although the mRNA levels of sst5 and sst2A in male rat pituitaries
      were higher than in females. Chronic administration (4 weeks) of E2 to the
      ovariectomized rats increased mRNA expression of sst2A, sst2B, sst3, and sst1 and
      drastically decreased expression of sst5; the transcripts of sst2 isoforms
      constituted 87% of total SRIF receptor subtype mRNAs (sst2A/GAPDH = 1.2 x 10(
      2)), whereas the sst5 mRNA level was less than 1%. Receptor-binding studies
      revealed that in pituitaries from both ovariectomized rats and male rats,
      heterogeneous receptor types, probably sst5 and sst2, were expressed, whereas
      receptors from E2-treated rat pituitaries mostly exhibited characteristics of the
      sst2 subtype. The results demonstrated that sst5 and sst2A were the major
      subtypes expressed in normal rat pituitaries with a sex-dependent difference and
      that whereas E2 up-regulates the expression of sst2 isoforms, it down-regulates
      the expression of sst5, suggesting roles for these subtypes in the control of
      pituitary functions.

PMID- 9528937
TI  - Influence of sex differences on the renal secretion of organic anions.
AB  - The kidney's responsiveness to male sexual hormones has been often neglected.
      Renal secretion of organic anions is higher in male than in female individuals;
      as a consequence, most of the xenobiotics that are excreted from the organism
      through this pathway are eliminated more rapidly by males than by female animals.
      To gain further insight into this issue, we studied in vitro and in vivo
      characteristics of the transport of p-aminohippurate (PAH), a suitable marker for
      this system, in male and female rats, under different hormonal conditions.
      Kinetics of PAH showed a shorter elimination half-time in male than in female
      rats (t(1/2el): male = 16.2 +/- 2.1 min, female = 25.7 +/- 4.5 min, P < 0.05).
      Castration of male rats increased t(1/2el) to a value similar to that of female
      rats (t(1/2el): orchiectomized rat = 28.1 +/- 7.1 min). Testosterone treatment of
      female rats increased the elimination rate to a value similar to that of male
      rats. In vitro PAH uptake by renal cortical slices from intact male rats was
      higher than that by slices from orchiectomized rats. Kinetic analyses of PAH
      uptake suggest that the difference was caused by a lower number of transporting
      molecules in orchiectomized than in intact animals, whereas the transporting
      capacity for each carrier was similar in male and in orchiectomized rats. Our
      results suggest that testosterone increases the number of functional carriers for
      PAH in the kidney.

PMID- 9528938
TI  - Association of gonadotropin receptor precursors with the protein folding
      chaperone calnexin.
AB  - The lutropin/choriogonadotropin receptor (LHR) and follitropin receptor (FSHR)
      are members of the superfamily of G protein-coupled receptors. The carboxyl half
      of each receptor is composed of the classical seven membrane spanning regions
      connected by intracellular and extracellular loops. In addition, each receptor
      contains a large extracellular domain. Despite the complexity of the structure of
      G protein-coupled receptors, little is known about how these receptors assume
      their correct conformations during biosynthesis. Although the role of chaperone
      proteins in the folding of other proteins has been well documented, their role in
      the folding of G protein-coupled receptors has been an enigma. To better
      understand the folding of the LH and FSH receptors, we examined their association
      with the general chaperone proteins calnexin, binding protein (BiP), and the 94
      kDa glucose-regulated protein (GRP94). Clonal 293 cell lines expressing
      comparably high levels of each receptor were solubilized, and the extracts were
      incubated with the appropriate antibody bound to Protein A-sepharose beads.
      Experiments were performed using two approaches: 1) coimmunoprecipitation of
      receptor/chaperone complexes with one of the antireceptor antibodies, then SDS
      PAGE and Western blotting using either anticalnexin or anti-KDEL (which
      recognizes BiP and GRP94) antibodies; or 2) coimmunoprecipitation of
      receptor/chaperone complexes with anticalnexin or anti-KDEL, then Western
      blotting with one of the antireceptor antibodies. Using these protocols, we found
      that the immature forms of both the rLHR and rFSHR are associated with calnexin,
      but little or no association was observed for either receptor with BiP or GRP94.
      These experiments show that the precursor forms of the wild-type LHR and FSHR can
      associate with calnexin, raising the possibility that this chaperone protein may
      facilitate in the folding of the gonadotropin receptors.

PMID- 9528939
TI  - Androgen receptor in mouse brain: sex differences and similarities in
      autoregulation.
AB  - The androgen receptor (AR) is generally considered an autoregulated protein.
      However, studies in brain have produced mixed results regarding sex differences,
      which should be present given the higher endogenous levels of androgens in males,
      and the effects of gonadectomy, which presumably should lead to a loss of AR.
      Resolving these issues is a necessary step in developing a model of AR regulation
      in the central nervous system and, more broadly, in determining how regulation of
      this receptor may mediate neural target tissue responsiveness to androgen. To
      further investigate these issues, the distribution, density, and regulation of
      neural AR were compared among male and female mice that were intact,
      gonadectomized, or gonadectomized and given testosterone propionate (TP) through
      immunocytochemical and Western blot analyses. Four brain areas that have been
      linked to the regulation of male-typical behavior were evaluated: bed nucleus of
      the stria terminalis, posterior aspect, medial preoptic area, and dorsal and
      ventral aspects of the lateral septum. In the immunocytochemical study,
      integrated particle density, which reflects the average intensity of AR staining,
      was assessed among the six groups 24 h after surgery using PG-21, a peptide-based
      AR antiserum. Major findings included regional differences in the intensity of
      immunostaining; a robust sexual dimorphism in each region, with males exhibiting
      more intense staining than females; a loss of AR in both sexes after gonadectomy,
      with more dramatic changes evident in males; and significant up-regulation of AR
      in response to TP that was equivalent in both sexes. The Western blot analyses of
      AR in limbic system extracts prepared from the six groups showed a pattern of
      differences that mirrored the immunocytochemical results, indicating that PG-21
      recognized both liganded and unliganded AR. In addition, a dose-response study,
      in which gonadectomized males and females were administered from 25-1000 microg
      TP, demonstrated a significant linear trend in up-regulation of AR in both males
      and females, with no sexual dimorphism in the response to hormone treatment.
      These results demonstrate that the regulation of AR in both male and female
      neural tissue is comparable and that the critical determinant of AR expression is
      the presence or absence of androgen.

PMID- 9528940
TI  - Progesterone advances the diurnal rhythm of tuberoinfundibular dopaminergic
      neuronal activity and the prolactin surge in ovariectomized, estrogen-primed rats
      and in intact proestrous rats.
AB  - A diurnal change of tuberoinfundibular dopaminergic (TIDA) neuronal activity
      exists in female rats, which is prerequisite for the estrogen-induced afternoon
      PRL surge. Because progesterone (P4) administered in the morning can advance and
      amplify the PRL surge, it is of interest to learn whether its action involves the
      TIDA neuron. In adult ovariectomized and estrogen-primed Sprague-Dawley rats, P4
      (2 mg/kg, s.c.), given at 0800 h, exhibited a significant effect in advancing and
      amplifying the afternoon PRL surge, as determined by both chronic catheterization
      and decapitation methods of blood sampling. The afternoon decrease of TIDA
      neuronal activity, as determined by 3,4-dihydroxyphenylacetic acid concentration
      in the median eminence, was also advanced from 1400 to 1300 h. These effects of
      P4 on PRL surge and TIDA neuronal activity were shown to be dose- (from 0.5-4
      mg/kg) and estrogen-dependent. To determine whether the effect of P4 was indeed
      acting via specific P4 receptor (PR), we used a PR antagonist, RU486, an
      antisense oligodeoxynucleotide (ODN) for PR messenger RNA (mRNA), and an antibody
      against PR in this study, to answer this question. Treatments of RU486 (5 mg x 3,
      s.c.) for 1-2 days before, and on the sampling day, were effective in
      antagonizing the effects of P4 on TIDA neuronal activity and on PRL secretion.
      Intracerebroventricular injection of an antisense ODN (4 nM) for PR mRNA or of an
      antibody (1:1 and 1:5) against PR for 2 days (24 and 48 h before decapitation)
      also were effective. Treatments of RU486 on the sampling day only, of sense ODN
      for PR mRNA, or of diluted PR antibody (1:10) were without significant effect.
      The involvement of P4 or PR on modulating the TIDA neuronal rhythm and the PRL
      surge also was shown in proestrous rats. In conclusion, P4 may play a significant
      modulatory role on rhythmic changes of the TIDA neuronal activity and the PRL
      surge in the female rats.

PMID- 9528941
TI  - Multiple splicing events involved in regulation of human aromatase expression by
      a novel promoter, I.6.
AB  - The expression of aromatase is regulated in a tissue-specific fashion through
      alternative use of multiple promoter-specific first exons. To date, eight
      different first exons have been reported in human aromatase, namely I.1., I.2,
      I.3. I.4, I.5, PII, 2a, and 1f. Recently, we have found a new putative exon I in
      a RACE-generated library of THP-1 cells and have conducted studies to
      characterize this new exon I. We confirmed that the constructs containing 
      1552/+17 or less flanking sequence of this exon function as a promoter in THP-1
      cells, JEG-3 cells and osteoblast-like cells obtained from a human fetus. Results
      of transfection assays using a series of deletion constructs and mutation
      constructs indicate that a 1-bp mismatch of the consensus TATA-like box (TTTAAT)
      and the consensus sequence of the initiator site, which is located 45 bp
      downstream of the putative TATA box, were functioning cooperatively as a core
      promoter. The putative transcription site was confirmed by the results of RT-PCR
      southern blot analysis. We examined the regulation and the expression of this
      exon, I.6, in several human cells and tissues by RT-PCR Southern blot analysis.
      THP-1 cells (mononuclear leukemic origin) and JEG-3 cells (choriocarcinoma
      origin) expressed exon I.6 in serum-free media. The level of expression was
      increased by serum and phorbol myristyl acetate (PMA) in both cell lines. Adipose
      stromal cells also expressed exon I.6 in the presence of PMA. In fetal
      osteoblasts, the expression of exon I.6 was increased most effectively by serum
      and less so by dexamethasone (DEX) + IL-1beta and DEX + IL-11, whereas induction
      by serum was suppressed by the addition of DEX. The level of expression was low
      in granulosa cells in culture and did not change with forskolin. On the other
      hand, dibutyryl cAMP suppressed PMA-stimulated expression of exon I.6 in THP-1
      cells and adipose stromal cells. This result supports the hypothesis that the
      expression of exon I.6 is regulated mainly via an AP-1 binding site that is found
      upstream of the initiator site of the promoter region. Expression of exon I.6
      specific transcripts was examined in several human tissues. Testis and bone
      obtained from normal adults expressed exon I.6. Testicular tumor and hepatic
      carcinoma expressed high levels of exon I.6, whereas granulosa cell tumor did
      not. Fetal liver and bone also showed a significant level of exon I.6 expression,
      but not so much as testicular tumor and hepatic tumor. Several splicing variants
      of exon I.6 were detected especially in THP-1 and JEG-3 cells, and to a lesser
      extent in primary cultures and tissue samples. These variants were identified as
      an unspliced form, a form spliced at the end of exon I.4, a form spliced at the
      end of exon I.3 (truncated) and a form spliced 220 bp downstream of the 3' end of
      exon I.6. The last variant revealed a new splicing site. Because most of the
      splicing variants contain the sequence specific for exon I.3, RT-PCR specific for
      exon I.3 can coamplify these splicing variants of exon I.6 transcripts. These
      results suggests that it is necessary to examine the expression of I.6 in tissues
      that are known to express exon I.3 such as breast adipose tissue, in which
      promoter usage of exon I of the aromatase gene switches from exon I.4 to I.3 in
      the course of malignant transformation.

PMID- 9528942
TI  - Analysis of the juxtamembrane dileucine motif in the insulin receptor.
AB  - Dileucine-containing motifs are involved in trans-Golgi sorting, lysosomal
      targeting, and internalization. Previously, we have shown that the dileucine
      motif (EKITLL, residues 982-987) in the juxtamembrane region of the insulin
      receptor is involved in receptor internalization. Substitution of alanine
      residues for Leu986 and Leu987 led to a 3- to 5-fold decrease in the ability of
      the receptors to mediate insulin uptake. In the current study, we show that
      mutation of the same motif to Met986Ser987, the sequence found in the homologous
      position in the type I insulin-like growth factor receptor, did not affect
      insulin uptake. Therefore, we inquired whether the sequence EKITMS as an isolated
      motif could mediate the targeting of a reporter molecule to endosomes and then
      lysosomes, as was shown previously with the EKITLL motif of the normal receptor.
      Chimeric molecules containing Tac antigen fused to different hexapeptide
      sequences showed distinct patterns of subcellular localization by
      immunofluorescence microscopy. Tac-EKITLL and Tac-EKITAA were found predominantly
      in lysosomes and the plasma membrane, respectively. In contrast, Tac-EKITMS was
      found at the plasma membrane, in the trans-Golgi network, and in endosomes, but
      only small amounts were found in lysosomes. Thus, the dileucine motif (EKITLL)
      plays an important role in directing endocytosis of the intact insulin receptor
      and in mediating efficient endocytosis and lysosomal targeting as an isolated
      motif. Substitution of AA for LL inhibits endocytosis and lysosomal targeting in
      both systems. In contrast, substitution of MS for LL permits rapid endocytosis in
      the intact receptor, but mediates modest endocytosis and very little targeting to
      lysosomes as an isolated motif. Our observations support the idea that sorting
      signals are recognized at multiple steps in the cell, and that specific amino
      acid substitutions may differentially affect each of these sorting steps.

PMID- 9528943
TI  - Proglucagon processing in an islet cell line: effects of PC1 overexpression and
      PC2 depletion.
AB  - Proglucagon (proG) is differentially processed in the A cells of the pancreas to
      yield glucagon, and in the L cells of the intestine to generate glicentin,
      oxyntomodulin, the incretin glucagon-like peptide (GLP)-1(7-36NH2) and the
      intestinotropin GLP-2. To establish roles for the prohormone convertases PC1 and
      PC2 in proG processing within the context of a physiological model, we created
      stable cell lines from an islet-derived cell line, InR1-G9. These cells express
      proG and PC2, but not PC1, messenger RNA (mRNA). InR1-G9 cells were stably
      transfected with PC1 or antisense PC2. Selection was carried out in G418 (InR1
      G9/PC1) or Zeocin (InR1-G9/ASPC2). Both PC1 mRNA and protein were highly
      expressed in InR1-G9/PC1 cells (P < 0.01-0.001) compared with wild-type (WT)
      cells. Cells transfected with ASPC2 demonstrated significant decreases in both
      PC2 mRNA (P < 0.001) and protein (P < 0.05) levels. ProG-derived peptides in WT,
      control, InR1-G9/PC1, and InR1-G9/ASPC2 cells were identified by HPLC and RIA.
      Overexpression of PC1 in InR1-G9 cells resulted in increased processing to
      glicentin (P < 0.01), oxyntomodulin (P < 0.05), and GLP-2 (P < 0.05).
      Interestingly, processing to GLP-1(7-36NH2) did not increase upon transfection of
      PC1. Transfection of InR1-G9 cells with ASPC2 resulted in the disappearance of
      glicentin (P < 0.05). However, production of glucagon was not altered by
      antisense deletion of PC2. Surprisingly, GLP-1(7-36NH2) production appeared to be
      augmented (P < 0.05) in InR1-G9/ASPC2 cells, whereas GLP-2 production was not
      altered. In conclusion, these studies establish the role of PC1 in the processing
      of proG to the intestinal proG-derived peptides. This study also establishes a
      role for PC2 in the production of glicentin; however, the liberation of glucagon
      appears to be mediated by another, yet to be identified, convertase.

PMID- 9528944
TI  - Modulation of insulin-like growth factor I mitogenic signaling in 3T3-L1
      preadipocyte differentiation.
AB  - Insulin-like growth factor I (IGF-I) stimulates mitogenesis in proliferating 3T3
      L1 preadipocytes. However, IGF-I functions to stimulate differentiation once
      growth arrest occurs at confluence. Epidermal growth factor (EGF) is also a
      potent mitogen in these cells, but inhibits differentiation of preadipocytes. We
      compared mitogenic signaling via the mitogen-activated protein kinase (MAPK)
      pathway in response to IGF-I or EGF in proliferating, growth-arrested, and
      differentiating 3T3-L1 cells. IGF-I stimulation of MAPK was rapid and maximal in
      proliferating 3T3-L1 preadipocytes, but decreased greatly in differentiating
      cells. EGF was more potent than IGF-I in stimulating MAPK activity in 3T3-L1
      cells, and activation of MAPK was maintained in differentiating cells. These
      results suggest an uncoupling of MAPK activation specific to IGF-I-mediated 3T3
      L1 preadipocyte differentiation. Studies of proximal signaling revealed Shc
      phosphorylation and Shc/Grb2 complex formation in IGF-I-treated proliferating,
      but not differentiating, cells. Insulin receptor substrate-1 phosphorylation
      after IGF-I treatment was present in proliferating, quiescent, and
      differentiating preadipocytes. Shc phosphorylation and Grb2 association after EGF
      treatment were present throughout all phases of growth. The change in IGF-I
      signaling via Shc phosphorylation and MAPK activity during 3T3-L1 differentiation
      indicates that loss of IGF-I mitogenic signaling via the MAPK pathway is part of
      the differentiation process.

PMID- 9528945
TI  - The acute suckling stimulus induces expression of neuropeptide Y (NPY) in cells
      in the dorsomedial hypothalamus and increases NPY expression in the arcuate
      nucleus.
AB  - Elevated neuropeptide Y (NPY) levels in the hypothalamus have been reported
      during lactation in the rat. The increase in NPY neuronal activity may be
      important in modulating a number of changes in hypothalamic neuronal function
      that are associated with lactation. The aims of the present study were to
      determine 1) if NPY neurons in the hypothalamus can be activated by the suckling
      stimulus; and 2) the time course of the activation in response to the suckling
      stimulus. In the first experiment, lactating rats were deprived of their 8-pup
      litters on day 9 post partum for 48 h. On day 11, the animals were divided into
      three groups and exposed to the suckling stimulus for varying periods of time up
      to 24 h. NPY neuronal activity was assessed by measuring changes in NPY messenger
      RNA (mRNA) levels, using in situ hybridization. NPY mRNA levels in the caudal
      portion of the hypothalamic arcuate nucleus (ARH) were approximately doubled by
      24 h of suckling. NPY mRNA levels in the rostral portion of the ARH were not
      affected by suckling throughout the time examined. In addition to increased NPY
      mRNA in the ARH, resuckling for as little as 3 h induced NPY mRNA expression in
      cells located dorsal and lateral to the compact zone of the dorsomedial nucleus
      of the hypothalamus (DMH). NPY expression in these cells was not observed in the
      nonresuckled controls. These data demonstrate that the acute suckling stimulus
      activates two specific populations of NPY neurons in the hypothalamus: in the
      caudal portion of the ARH and in the DMH. The increased NPY neuronal activity may
      play an important role in modulating changes in hypothalamic regulation of
      hormone secretion and food intake.

PMID- 9528946
TI  - Intracellular signaling pathways confer specificity of transactivation by
      mineralocorticoid and glucocorticoid receptors.
AB  - The glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR) bind
      similar ligands and target genes in vitro yet have distinct roles in vivo. With a
      single exception, known mechanisms conferring specificity have been limited to
      prereceptor mechanisms. These alone cannot account for specificity, particularly
      at a transcriptional level. These studies aimed to determine whether receptor
      specific transcriptional regulation via physiological modulators of cellular
      signaling pathways, and MR-, as well as GR-specific interactions, could be
      demonstrated. By comparing modulation of GR- and MR-mediated transactivation in
      renal LLC-PK1 cells, we have identified several activators of intracellular
      signaling pathways that discriminate between the GR and the MR and demonstrate
      that differential regulation occurs at relatively specific points in the
      signaling pathway. The phosphatase inhibitor, okadaic acid, and the protein
      kinase G activator, sodium nitroprusside, stimulate only GR-mediated
      transactivation, in contrast to modulators of other protein kinase pathways that
      act in parallel on both receptors. The GR-specific effect of okadaic acid is
      observed only at doses where both phosphatases 1 and 2A are inhibited. MR
      specific modulators include a centrally active alpha-2 adrenergic agonist and the
      thyroid receptor. Comparison of the interaction between the thyroid receptor and
      the GR, or the MR, distinguish two types of repression, only one of which is
      receptor-specific. These studies identify several signal transduction pathways
      that can differentially activate either the MR or the GR at a transcriptional
      level and might play physiological roles in conferring MR- or GR-specific
      regulation.

PMID- 9528947
TI  - Molecular characterization of equine prostaglandin G/H synthase-2 and regulation
      of its messenger ribonucleic acid in preovulatory follicles.
AB  - To increase our understanding of the molecular control of PG synthesis in equine
      preovulatory follicles, the specific objectives of this study were to clone and
      determine the primary structure of equine prostaglandin G/H synthase-2 (PGHS-2)
      and to characterize the regulation of PGHS-2 messenger RNA (mRNA) in follicles
      before ovulation. A complementary DNA (cDNA) library prepared from follicular
      mRNA and a genomic library were screened with a mouse PGHS-2 cDNA probe to
      isolate the equine PGHS-2 cDNA and gene, respectively. The expression library
      yielded three nearly full-length clones that differed only in their 5'-ends;
      clones 3, 5, and 6 were 2946, 3138, and 3398 bp in length, respectively. The
      longest clone was shown to start 9 bp downstream of the transcription initiation
      site, as determined by primer extension analysis, and to contain 120 bp of 5'
      untranslated region (UTR), 1812 bp of open reading frame, and 1466 bp of 3'-UTR.
      The open reading frame encodes a 604-amino acid protein that is more than 80%
      identical to PGHS-2 homologs in other species. Numerous repeats (n = 11) of the
      Shaw-Kamen's sequence (ATTTA) are present in the 3'-UTR, a motif typically
      indicative of mRNAs with a short half-life. The complete equine PGHS-2 gene was
      isolated and sequenced from a approximately 17-kilobase clone obtained from the
      genomic library. The equine PGHS-2 gene structure (10 exons and 9 introns; total
      length of 6991 bp) is similar to its human homolog except for lacking sequence
      elements in introns 4, 8, and 9 and in the 3'-UTR region of exon 10. To
      characterize the regulation of PGHS-2 mRNA in equine follicles before ovulation,
      preovulatory follicles were isolated during estrus, 0, 12, 24, 30, 33, 36, and 39
      h (n = 4-5 follicles/time point) after an ovulatory dose of hCG. Results from
      Northern blots showed significant changes in steady state levels of PGHS-2 mRNA
      in preovulatory follicles after hCG treatment (P < 0.05). The transcript remained
      undetectable between 0-24 h post-hCG, first appeared (approximately 4 kilobases)
      only at 30 h, and reached maximal levels 33 h post-hCG. PGHS-2 mRNA was
      selectively induced in granulosa cells and not in theca interna. Thus, this study
      provides for the first time the primary structure of the equine PGHS-2 gene,
      transcript, and protein. It also demonstrates that the induction of PGHS-2 gene
      expression in equine granulosa cells is a long molecular process (30 h post-hCG),
      thereby providing a model to study the molecular basis for the late
      transcriptional activation of PGHS-2 in species with a long ovulatory process.

PMID- 9528948
TI  - Regulation of the epidermal growth factor receptor in fetal rat lung fibroblasts
      during late gestation.
AB  - Lung epithelial cell differentiation is predominantly regulated by mesenchymal
      epithelial cell communication. We have previously shown that epidermal growth
      factor (EGF) positively influences this process, and that EGF receptor (EGF-R)
      binding in fetal rat lung fibroblasts peaks on d18-19 of gestation, just before
      the onset of augmented surfactant synthesis. This regulation of EGF-R in late
      gestation fetal lung fibroblasts may control the timing of mesenchymal-epithelial
      cell communication leading to surfactant synthesis. Hormones and growth factors
      exert positive and negative influences on lung development, but whether they
      regulate the EGF-R is unknown. We hypothesized that positive [EGF, cortisol,
      retinoic acid (RA)] and negative [transforming growth-factor-beta1 (TGF-beta1),
      dihydrotestosterone (DHT)] regulators of lung cell development regulate the EGF-R
      in the fetal lung. We studied EGF-R binding and protein abundance in sex-specific
      fetal rat lung fibroblasts cultured at d17, d19, and d21. EGF-R binding was
      significantly elevated after RA (both sexes d17 and d19, females d21) and after
      DHT (females d19) treatment. EGF and cortisol had minimal or inhibitory effects
      on EGF-R binding. Western blot analysis showed that the observed changes in EGF-R
      binding were associated with similar changes in EGF-R protein. We conclude that
      factors that affect lung maturation continue to regulate EGF-R in a
      developmental, sex-specific manner during late gestation.

PMID- 9528949
TI  - Molecular cloning and characterization of the porcine calcitonin gene-related
      peptide receptor.
AB  - Calcitonin gene-related peptide (CGRP) receptors (CGRP-Rs) are widely distributed
      throughout the central and peripheral nervous systems. A novel CGRP-R was
      identified from a porcine lung complementary DNA library. Sequence analysis
      indicated that the CGRP-R is 462 amino acids in length and shares 93% sequence
      identity with the human CGRP-R. Northern blot analysis indicated a messenger RNA
      species of 5.4 kilobases, which is abundantly expressed in the lung. Ligand
      binding studies of the cloned CGRP-R expressed in human embryonic kidney (HEK
      293) cells showed the presence of high affinity receptor for CGRP with a Kd of
      38.5 pM. The pharmacological profiles of various ligands competing for [125I]CGRP
      binding to the expressed receptor were in accordance with those for the natural
      receptor. Binding of [125I]CGRP to the expressed receptor was decreased in the
      presence of a nonhydrolyzable analog of GTP, guanosine 5' (gamma-thio)
      triphosphate. In functional studies, CGRP stimulated the activation of adenylyl
      cyclase with an EC50 of 2.5 nM. The linear analog of CGRP, diacetoamidomethyl
      cysteine CGRP, did not affect adenylyl cyclase activity on its own or in the
      presence of CGRP. Furthermore, the CGRP receptor antagonists, CGRP-(8-37)alpha,
      inhibited the CGRP-mediated response in a competitive manner. Collectively, the
      binding and functional data demonstrate that we have cloned a porcine CGRP type 1
      receptor. The availability of the CGRP-R complementary DNA will allow us to
      examine its participation in pathophysiological processes.

PMID- 9528950
TI  - Characterization of a region upstream of exon I.1 of the human CYP19 (aromatase)
      gene that mediates regulation by retinoids in human choriocarcinoma cells.
AB  - The biosynthesis of estrogens is catalyzed by aromatase P450 (P450arom), the
      product of the CYP19 gene. The tissue-specific expression of the CYP19 gene is
      regulated by means of tissue-specific promoters through the use of alternative
      splicing mechanisms. Thus, transcripts containing various 5'-untranslated termini
      are present in ovary, brain, adipose stromal cells, and placenta. Sequence
      corresponding to untranslated exon I.1 is present uniquely in 5'-termini of
      transcripts expressed in human placenta and choriocarcinoma cells, as a
      consequence of expression driven by a distal promoter, I.1. The goal of the
      present study was the identification of regulatory elements in this promoter
      region. Various deletion mutations of the upstream flanking region of exon I.1
      were constructed using the PCR or restriction enzyme digestion. The genomic
      fragments were fused upstream of the luciferase reporter gene. These constructs
      were transfected into human choriocarcinoma (JEG3) cells. The longest construct
      employed, -924/+10 bp, expressed the highest luciferase reporter gene activity.
      The -64/+10 bp and -125/+10 bp constructs showed no reporter gene expression.
      Transfection of the -201/+10 bp construct resulted in reporter gene expression,
      but at a lower level than that of the -924/+10 bp construct, and this expression
      was induced by serum as well as by LG69 and TTNPB, ligands specific for RXR and
      RAR respectively, as well as by vitamin D. These results parallel the actions of
      the ligands on aromatase activity. Mutation or deletion of an imperfect
      palindromic sequence (AGGTCATGCCCC) located at -183 to -172 bp upstream of the
      transcriptional start site of exon I.1 resulted in loss of basal- and retinoid
      induced reporter gene expression. Gel retardation analysis using nuclear extracts
      of JEG3 cells treated with retinoids and the imperfect palindromic sequence as
      probe, showed that proteins present in the nuclear extracts bound to this
      sequence in a specific fashion. The binding activities were elevated by
      incubation of the cells with LG69 and TTNPB, ligands specific for RXR and RAR
      respectively. Binding of nuclear proteins to the palindromic sequence was
      displaced either by anti-RXR alpha serum or by anti-VDR serum, suggesting the
      formation of a heterodimer of RXR alpha and VDR. These results suggest that the
      imperfect palindromic sequence upstream of exon I.1 plays an important but novel
      role in the regulated expression of the CYP19 gene in choriocarcinoma cells.

PMID- 9528951
TI  - Molecular cloning and hormonal regulation of PiT-1, a sodium-dependent phosphate
      cotransporter from rat parathyroid glands.
AB  - The extracellular concentration of inorganic phosphate (Pi) is an important
      determinant of parathyroid cell function. The effects of Pi may be mediated
      through specific molecules in the parathyroid cell membrane, one candidate
      molecule for which would be a Na+-dependent Pi cotransporter. A complementary DNA
      encoding a Na+-Pi cotransporter, termed rat PiT-1, has now been isolated from rat
      parathyroid. The 2890-bp complementary DNA encodes a protein of 681 amino acids
      that shows sequence identities of 97% and 93% with the type III Na+-Pi
      cotransporters mouse PiT-1 and human PiT-1, respectively. Expression of rat PiT-1
      in Xenopus oocytes revealed that it possesses Na+-dependent Pi cotransport
      activity. PiT-1 messenger RNA (mRNA) is widely distributed in rat tissues and is
      most abundant in brain, bone, and small intestine. The amount of PiT-1 mRNA in
      the parathyroid of vitamin D-deficient rats was reduced compared with that in
      normal animals and increased markedly after administration of 1,25
      dihydroxyvitamin D3. Furthermore, the abundance of PiT-1 mRNA in the parathyroid
      was much greater in rats fed a low-Pi diet than in those fed a high-Pi diet.
      Thus, rat PiT-1 may contribute to the effects of Pi and vitamin D on parathyroid
      function.

PMID- 9528952
TI  - Contact-dependent cell interactions determine hormone responsiveness and
      desensitization in rat granulosa cells.
AB  - The maintenance of associations between granulosa cells (GCs) is necessary for
      FSH-stimulated induction of LH receptors. In cultures in which these associations
      have been disrupted, FSH fails to induce LH receptors. As FSH exerts its action
      in GCs via cAMP, we have examined if the aggregation state of GCs plays a role in
      modulating FSH-stimulated cAMP production. GCs were obtained from the ovaries of
      diethylstilbestrol-primed immature rats. Cells were prepared as aggregate or
      dispersed populations by isolating GCs in either the presence or absence of Ca2+.
      Nonviable cells were removed by a brief exposure to trypsin. We have shown
      previously that trypsin treatment in the absence of Ca2+ removes a class of cell
      adhesion molecules, termed cadherins, from the plasma membranes of GCs. Hence,
      the dispersed GCs are incapable of reaggregating. Dispersed or aggregate GC
      preparations were incubated with different doses of human FSH (0-1 microg) for 0
      60 min in the presence of isobutylmethylxanthine, a phosphodiesterase inhibitor.
      Incubations were terminated, and the cAMP accumulated was measured using a
      specific RIA. As desensitization to hormonal stimuli is a characteristic property
      of many G protein-coupled response systems, cAMP production of cell aggregates
      and dispersed cells in response to a repeated stimulation with FSH was assessed.
      Our results indicate that aggregate GCs have a significantly attenuated cAMP
      response to all doses of FSH compared with dispersed GC preparations. Changing
      cell densities did not alter the nature of these responses, indicating that
      nonspecific cell interactions were not responsible for this difference. The
      number of FSH receptors and their affinity were unaltered in the two cell
      preparations. Cholera toxin- and forskolin-stimulated cAMP production were
      similar in the two preparations, demonstrating that the changes in responsiveness
      did not arise from alterations in G protein activation or adenylate cyclase
      activity. Only the aggregate GCs could be desensitized. The dispersed cells
      displayed undiminished cAMP responsiveness to a second FSH stimulation. Finally,
      culture of the GC preparations with cholera toxin induced LH receptors in GC
      aggregates only. LH receptor induction in dispersed cell cultures required the
      addition of estradiol. These results indicate that contact-dependent cell
      interactions can modulate GC cAMP production in response to FSH. cAMP responses,
      however, were not the sole determinant of cell differentiation, as assessed by LH
      receptor induction. We speculate that cell-cell interactions within the
      follicular epithelium are important determinants for cell differentiation leading
      to follicle selection for ovulation or atresia.

PMID- 9528953
TI  - Insulin-like growth factor-binding protein-5 is cleaved by physiological
      concentrations of thrombin.
AB  - Insulin-like growth factor (IGF)-binding protein-5 (IGFBP-5) is cleaved by a
      serine protease that is secreted by fibroblasts and porcine smooth muscle cells
      (pSMC) in culture. To investigate whether other serine proteases could cleave
      this substrate at physiologically relevant concentrations, we determined the
      proteolytic effects of thrombin on IGFBP-5. Human alpha-thrombin (0.0008 NIH
      U/ml) cleaved IGFBP-5 into 24-, 23-, and 20-kDa non-IGF-I-binding fragments.
      Cleavage occurred at a physiologically relevant thrombin concentration. The
      effect was specific for IGFBP-5, as other forms of IGFBPs, e.g. IGFBP-1, IGFBP-2,
      and IGFBP-4 were not cleaved by thrombin. Although IGFBP-3 was cleaved by
      thrombin, this effect required a 50-fold greater thrombin concentration.
      [35S]Methionine labeling followed by immunoprecipitation confirmed that IGFBP-5
      that was constitutively synthesized by pSMC cultures was also degraded by
      thrombin into 24-, 23-, and 20-kDa fragments. The binding of IGF-I to IGFBP-5
      partially inhibited IGFBP-5 degradation by thrombin, and an IGF analog that does
      not bind to IGFBP-5 had no effect. Thrombin did not account for the serine
      protease activity that had been shown previously to be present in pSMC
      conditioned medium. This was proven by showing that 1) no immunoreactive thrombin
      could be detected in the pSMC-conditioned medium; 2) the IGFBP-5 fragments that
      were generated by thrombin showed three cleavage sites (Arg192-Ala193, Arg156
      Ile157, and Lys120-His121), whereas the serine protease in conditioned medium
      cleaves IGFBP-5 at a different site; and 3) hirudin had no effect on IGFBP-5
      cleavage by the protease in pSMC medium; however, it inhibited IGFBP-5
      degradation by thrombin. To determine the physiological significance of IGFBP-5
      cleavage, the effect of an IGFBP-5 mutant that is resistant to cleavage by the
      pSMC protease and has been shown to inhibit IGF-I actions in pSMC was determined.
      This mutant inhibited IGF-I-stimulated DNA synthesis, but if thrombin was added
      simultaneously, IGF-I was fully active. In summary, physiological concentrations
      of thrombin degrade IGFBP-5. Degradation can be blocked by hirudin and is
      partially inhibited by IGF-I binding. Generation of active thrombin in vessel
      walls may be a physiologically relevant mechanism for controlling IGF-I
      bioactivity.

PMID- 9528954
TI  - Activation of transcriptionally active nuclear factor-kappaB by tumor necrosis
      factor-alpha and its inhibition by antioxidants in rat thyroid FRTL-5 cells.
AB  - ABSTRACT Tumor necrosis factor-alpha (TNF-alpha) exerts pleiotropic effects on
      thyroid follicular cells. However, the intracellular signaling pathway for the
      TNF-alpha action has not been well elucidated. The present study examined the
      effects of TNF-alpha on the activation of nuclear factor-kappa B (NF-kappaB) and
      on the expression of interleukin (IL)-6 gene in rat thyroid FRTL-5 cells. The
      treatment of the cells with TNF-alpha resulted in the nuclear translocation of
      p65-p50 heterodimer as well as p50-p50 homodimer NF-kappaBs. The treatment with
      the antioxidants 20 mM N-acetyl-L-cysteine (NAC) and 10 microM pyrrolidine
      dithiocarbamate (PDTC) inhibited the TNF-alpha-dependent activation of p65-p50
      heterodimer but not the p50-p50 homodimer, indicating that generation of oxidants
      is required for the activation of the heterodimer NF-kappaB. When the plasmid
      containing the multimerized NF-kappaB sites upstream of a luciferase reporter
      gene was transfected into FRTL-5 cells, the treatment with NAC or PDTC prevented
      the TNF-alpha-dependent increase in the luciferase activities, indicating that
      the p65-p50 heterodimer is a transcriptionally active NF-kappaB. Accordingly, the
      TNF-alpha-dependent increase in IL-6 messenger RNA and in secretion of the
      protein was prevented by the treatment with NAC. These results strongly suggest
      that TNF-alpha increases the IL-6 gene expression through the activation of NF
      kappaB in the thyroid cells, and that antioxidants suppress the TNF-alpha
      dependent IL-6 expression by inhibiting the activation of the transcriptionally
      active NF-kappaB.

PMID- 9528955
TI  - A novel interaction between inhibitory melatonin receptors and protein kinase C
      dependent signal transduction in ovine pars tuberalis cells.
AB  - This study revealed an important and unexpected finding: namely, that inhibitory
      melatonin receptors can inhibit a phorbol 12,13 myristate acetate (PMA)-induced,
      protein kinase C (PKC)-dependent increase in c-fos messenger RNA expression in
      ovine pars tuberalis (PT) cells. PMA induces dose-dependent stimulation of c-fos
      expression that is attenuated by melatonin in a dose-dependent and pertussis
      toxin-sensitive manner. The effect of 100 nM PMA is blocked by Ro31-8220 (1
      microM), yet is not mimicked by 4alpha-PMA (100 nM). PMA (100 nM) induces PKC
      activity in PT cells (P < 0.05) within 5 min, but melatonin has no effect on this
      response. PMA (100 nM) stimulates both phospholipase D and mitogen-activated
      protein kinase (MAPK) (p42/44) activities in PT cells, but melatonin has no
      effect on these responses. The results indicate that neither of these second
      messenger activities contribute to the melatonin-sensitive pathway of c-fos
      activation. The MEK (MAPK kinase) inhibitor, PD98059 (50 microM), does not block
      the induction of c-fos by PMA, although at the same dose it inhibits PMA-mediated
      activation of p42/44 MAPK by 50-70%, and activation by forskolin or insulin-like
      growth factor-I by 100%. These data suggest that p42/44 MAPK may not be the
      primary mediator of PKC-dependent c-fos induction. In contrast to the effect of
      melatonin on PMA-mediated c-fos induction in PT cells, in L cells stably
      transfected with the sheep Mel1 alphabeta receptor, melatonin potentiates the c
      fos response in a pertussis toxin-sensitive manner. These data indicate the
      tissue-specific nature of melatonin receptor signaling, and reveal that a
      pertussis toxin-sensitive pathway can block PKC-mediated c-fos induction in PT
      cells.

PMID- 9528956
TI  - Mechanism of action of pituitary adenylate cyclase-activating polypeptide on
      human glycoprotein hormone alpha-subunit transcription in alphaT3-1 gonadotropes.
AB  - Pituitary adenylate cyclase activating polypeptide (PACAP) has been shown to
      increase glycoprotein hormone alpha-subunit synthesis and release from pituitary
      cells. We have used alphaT3-1 clonal gonadotropes to investigate the
      intracellular mechanisms involved in PACAP regulation of alpha-subunit gene
      transcription; and using deletion, mutation, and heterologous constructs of the
      alpha-promoter linked to a luciferase reporter gene, we have defined DNA
      sequences responsive to PACAP. Stimulation of alphaT3-1 cells for 24 h with
      PACAP, GnRH, or vasoactive intestinal peptide (VIP) resulted in a time- and
      concentration-dependent increase in alpha-promoter transcription at 100 nM for
      GnRH (17.5-fold, P < 0.001), PACAP (12.7-fold, P < 0.01), and VIP (4.1-fold, P <
      0.05). Incubation of alphaT3-1 cells in calcium-depleted medium suggested that
      the transcriptional response to PACAP was less dependent on changes in
      intracellular calcium concentration, in contrast to the results seen with GnRH or
      VIP, where alpha-subunit transcription was significantly reduced. Transfection of
      an alpha-promoter construct containing a mutant cAMP response element (CRE)
      suggested that the CRE region is involved in PACAP and VIP responsiveness, with
      stimulatory effects on the mutant construct by PACAP (11.1-fold) and VIP (7.6
      fold) being significantly (P < 0.001) reduced, compared with their stimulatory
      effects (PACAP: 25.6-fold, VIP: 23.1-fold) on the native alpha-promoter. In the
      same experiment, the transcriptional response of the mutant CRE construct and the
      native CRE construct to GnRH was not significantly different. Both PACAP and VIP
      enhanced GnRH-stimulated alpha-subunit gene transcription, but this additive
      effect was lost when their combined effects on the mutant CRE were examined.
      Deletion analysis indicated that sequences between -244 and -195 bp were involved
      in mediating the response to PACAP, with a dramatic reduction in fold-stimulation
      by PACAP (2.0-fold) of the -195-bp construct, compared with the -244-bp construct
      (15.8-fold). Constructs containing only upstream alpha-promoter sequences from 
      517 bp to -98 bp, fused to the heterologous thymidine kinase promoter, exhibited
      a similar loss of responsiveness to PACAP below -298 bp. Thus, our studies show
      that, unlike GnRH, PACAP stimulation of alpha-subunit gene transcription in
      alphaT3-1 cells is less dependent on changes in intracellular calcium
      concentration; and full transcriptional activation of the alpha-subunit by PACAP
      requires an intact CRE. PACAP responsiveness involves sequences between -244 and 
      195 bp of the alpha-promoter. These sequences have been implicated also in GnRH
      responsiveness and may thus provide a mechanism for coordinated regulation of the
      alpha-subunit gene by PACAP and GnRH in alphaT3-1 cells.

PMID- 9528957
TI  - Ontogeny of region-specific sex differences in androgen receptor messenger
      ribonucleic acid expression in the rat forebrain.
AB  - Testosterone and its metabolites are the principal gonadal hormones responsible
      for sexual differentiation of the brain. However, the relative roles of the
      androgen receptor (AR) vs. the estrogen receptor in specific aspects of this
      process remain unclear due to the intracellular metabolism of testosterone to
      active androgenic and estrogenic compounds. In this study, we used an 35S-labeled
      riboprobe and in situ hybridization to analyze steady state, relative levels of
      AR messenger RNA (mRNA) expression in the developing bed nucleus of the stria
      terminalis, medial preoptic area, and lateral septum, as well as the ventromedial
      and arcuate nuclei of the hypothalamus. Each area was examined on embryonic day
      20 and postnatal days 0, 4, 10, and 20 to produce a developmental profile of AR
      mRNA expression. AR mRNA hybridization was present on embryonic day 20 in all
      areas analyzed. In addition, AR mRNA expression increased throughout the
      perinatal period in all areas examined in both males and females. However,
      between postnatal days 4 and 10, sharp increases in AR mRNA expression in the
      principal portion of the bed nucleus of the stria terminalis and the medial
      preoptic area occurred in the male that were not paralleled in the female.
      Subsequently, males exhibited higher levels of AR mRNA than females in these
      areas by postnatal day 10. There was no sex difference in AR mRNA content in the
      lateral septum, ventromedial nucleus, or arcuate nucleus at any age. These
      results suggest that sex differences in AR mRNA expression during development may
      lead to an early sex difference in sensitivity to the potential masculinizing
      effects of androgen.

PMID- 9528958
TI  - Hemodynamic, hormonal, and renal effects of intracerebroventricular
      adrenomedullin in conscious sheep.
AB  - Adrenomedullin, the recently described vasodilator that exhibits potent
      hypotensive actions when administered systemically, is also found in the central
      nervous system, suggesting a role for adrenomedullin as a neurohormone. However,
      only a limited number of studies have examined the central effects of
      adrenomedullin. Therefore, we have examined the integrative hemodynamic, renal,
      and hormonal effects of intracerebroventricular (I.C.V.) adrenomedullin in
      conscious sheep. Eight surgically prepared sheep received I.C.V. infusions of
      adrenomedullin at two doses (2 ng/kg x min followed immediately by 20 ng/kg x min
      each for 90 min) in a vehicle-controlled study. Water deprivation for 48 h before
      control infusion resulted in sheep drinking 2617 +/- 583 ml in the 90-min period
      following reintroduction of water. On the adrenomedullin day, drinking was halved
      to 1392 +/- 361 ml (P < 0.05). Adrenomedullin had no significant effect on
      urinary volume and sodium excretion. Plasma adrenomedullin levels remained
      unchanged during control infusions but were elevated by the end of I.C.V.
      adrenomedullin infusions (P < 0.001). Plasma ANP levels were also increased
      approximately 50% (P < 0.05). Plasma levels of both ACTH and cortisol were also
      increased 3- to 4-fold in response to I.C.V. adrenomedullin (P < 0.05). There was
      no significant difference in arterial pressure, heart rate, or cardiac output
      between study days. In conclusion, adrenomedullin within the central nervous
      system may have at least two roles: modulation of the hypothalamo-pituitary
      adrenal axis and protection against fluid overload.

PMID- 9528959
TI  - Evidence that the mediobasal hypothalamus is the primary site of action of
      estradiol in inducing the preovulatory gonadotropin releasing hormone surge in
      the ewe.
AB  - Although a neural site of action for estradiol in inducing a LH surge via a surge
      of GnRH is now well established in sheep, the precise target(s) for estrogen
      within the brain is unknown. To address this issue, two experiments were
      conducted during the breeding season using an artificial model of the follicular
      phase. In the first experiment, bilateral 17beta-estradiol microimplants were
      positioned in either the medial preoptic area (MPOA) or the mediobasal
      hypothalamus (MBH), and LH secretion was monitored. An initial negative feedback
      inhibition of LH secretion was observed in ewes that had estradiol microimplants
      located in the MPOA (6 of 6 ewes) or caudal MBH in the vicinity of the arcuate
      nucleus (4 of 4). In contrast, a normal LH surge was only found in animals
      bearing estradiol microimplants in the MBH (5 of 10). Detailed analysis of
      estradiol microimplant location with respect to the estrogen receptor-alpha
      immunoreactive cells of the hypothalamus revealed that 4 of the 5 ewes exhibiting
      a LH surge had microimplants located bilaterally within or adjacent to the area
      of estrogen receptor-expressing cells of the ventromedial nucleus. Two of these
      ewes exhibited a LH surge without showing any form of estrogen negative feedback.
      In the second experiment, we used the technique of hypophyseal portal blood
      collection to monitor GnRH secretion directly at the time of the LH surge induced
      by estradiol delivered either centrally or peripherally. Central estradiol
      implants induced the GnRH surge. The duration and mean plasma concentration of
      GnRH during the surge were not different between animals given peripheral or
      central MBH estradiol implants. Cholesterol-filled MBH microimplants did not
      evoke a GnRH surge. We conclude that the ventromedial nucleus is the primary site
      of action for estradiol in stimulating the preovulatory GnRH surge of the ewe,
      whereas the MPOA and possibly the caudal MBH are sites at which estrogen can act
      to inhibit LH secretion. These data provide evidence for the sites within the
      ovine hypothalamus responsible for mediating the bimodal influence of estradiol
      on GnRH secretion and suggest that different, and possibly independent, neuronal
      cell populations are responsible for the negative and positive feedback actions
      of estradiol.

PMID- 9528960
TI  - The human analog of murine cystein rich protein 61 [correction of 16] is a
      1alpha,25-dihydroxyvitamin D3 responsive immediate early gene in human fetal
      osteoblasts: regulation by cytokines, growth factors, and serum.
AB  - 1Alpha,25-dihydroxyvitamin D3 (1,25-(OH)2D3) is a potent mediator of
      differentiation and maintenance of specific functions of osteoblasts. To detect
      novel targets for 1,25-(OH)2D3 action, we applied differential display PCR to
      human fetal osteoblast-like cells and identified the human analog of murine
      cystein rich protein 61 (hCYR61) as a 1,25-(OH)2D3-responsive immediate early
      gene in differentiated fetal osteoblast-like cells. The murine gene CYR61 is
      important for cell-cell and cell-matrix interactions, and it belongs to an
      emerging gene family of cysteine-rich proteins. hCYR61 messenger RNA (mRNA)
      steady-state levels were stimulated 11-fold by 10 nM 1,25-(OH)2D3 by 1 h and
      declined to control levels by 4 h. This transient stimulation of hCYR61 mRNA was
      not inhibited by cycloheximide but was prevented by actinomycin D, indicating
      that the 1,25-(OH)2D3 effect involves transcriptional events and does not require
      de novo protein synthesis. hCYR61 mRNA stability was not influenced by
      1,25(OH)2D3, whereas cycloheximide treatment stabilized hCYR61 mRNA. FCS, as well
      as growth factors and cytokines such as basic fibroblast growth factor, epidermal
      growth factor, tumor necrosis factor alpha, and interleukin-1, strongly elevated
      hCYR61 mRNA steady-state levels within 1 h. hCYR61 mRNA was expressed also in
      primary human osteoblasts and osteosarcoma cell lines. Using a commercial tissue
      blot, hCYR61 mRNA was only observed in skeletal muscle. The fast and transient
      response of hCYR 61 to 1,25-(OH)2D3, serum, growth factors, and cytokines
      suggests an important role of hCYR61 for osteoblast function and differentiation.

PMID- 9528961
TI  - Gonadal steroids and hypothalamic galanin and neuropeptide Y: role in eating
      behavior and body weight control in female rats.
AB  - The neuropeptides, galanin (GAL) and neuropeptide Y (NPY), based on studies in
      male rodents, are believed to have a role in controlling energy balance, both
      nutrient ingestion and metabolism. Whereas these peptides are also involved in
      reproduction, little is known about their specific function in energy balance in
      females. In rats consuming lab chow or macronutrient diets, measurements across
      the estrous cycle were taken of hypothalamic GAL and NPY, using RIA and
      immunohistochemistry; of the circulating hormones, estradiol, progesterone, and
      LH; and also of food intake and body weight. Levels of GAL and NPY peak during
      the proestrous phase of the female cycle when circulating estradiol and
      progesterone also rise. As previously reported for GAL, this peak is detected in
      two areas, the medial preoptic area (MPOA; +110%; P < 0.05) and the external zone
      of the median eminence (+57%; P < 0.05). In addition, this proestrous peak is
      seen in the paraventricular nucleus (PVN), specifically the anterior
      parvocellular portion (+35%; P < 0.05). Similarly, NPY rises during proestrous in
      the medial region of the PVN (+21%; P < 0.05) in addition to the MPOA (+78%; P <
      0.05) and arcuate nucleus (+35%; P < 0.05). This peak in peptide levels is
      accompanied by an increase in caloric intake in rats receiving the lab chow diet
      and a specific increase in preference for fat in rats receiving macronutrient
      diets. Animals showing a preference for a fat-rich diet exhibit higher levels of
      GAL in the MPOA as well as the PVN and median eminence and also of NPY
      specifically in the MPOA. These peptides in the MPOA are similarly enhanced in
      animals with greater body fat, independent of diet. This evidence suggests that
      in the female rat, both GAL and NPY in the MPOA may contribute to the overeating
      and increased weight gain that occur during a fat-rich diet.

PMID- 9528962
TI  - Potential regulatory roles for G protein-coupled receptor kinases and beta
      arrestins in gonadotropin-releasing hormone receptor signaling.
AB  - GnRH stimulates gonadotropin secretion, which desensitizes unless the releasing
      hormone is secreted or administered in a pulsatile fashion. The mechanism of
      desensitization is unknown, but as the GnRH receptor is G protein coupled, it
      might involve G protein-coupled receptor kinases (GRKs). Such kinases
      phosphorylate the intracellular regions of seven-transmembrane receptors,
      permitting beta-arrestin to bind, which prevents the receptor from activating G
      proteins. Here, we tested the effect of GRKs and beta-arrestins on GnRH-induced
      inositol trisphosphate (IP3) production in COS cells transfected with the GnRH
      receptor complementary DNA. GRK2, -3, and -6 overexpression inhibited IP3
      production by 50-75% during the 30 sec of GnRH treatment. Coexpression of GRK2
      and beta-arrestin-2 suppressed GnRH-induced IP3 production more than that of
      either alone. Immunocytochemical staining of rat anterior pituitary revealed that
      all cells expressed GRK2, -3, and -6; all cells also expressed the beta
      arrestins. Western blots on cytosolic extracts of rat pituitaries revealed the
      presence of GRK2/3 and beta-arrestin-1 and -2. The expression of GRKs and beta
      arrestins by gonadotropes and their inhibition of GnRH-stimulated IP3 production
      in COS-1 cells expressing the GnRH receptor suggest a potential regulatory role
      for the GRK/beta arrestin paradigm in GnRH receptor signaling.

PMID- 9528963
TI  - Penetration of dexamethasone into brain glucocorticoid targets is enhanced in
      mdr1A P-glycoprotein knockout mice.
AB  - Mice with a genetic disruption of the multiple drug resistance (mdr1a) gene were
      used to examine the effect of the absence of its drug-transporting P-glycoprotein
      product from the blood-brain barrier on the distribution and cell nuclear uptake
      of [3H]-dexamethasone in the brain. [3H]-dexamethasone (4 microg/kg mouse) was
      administered s.c. to adrenalectomized mdr1a (-/-) and mdr1a (+/+) mice. One hour
      later, the mice were decapitated, and the radioactivity was measured in
      homogenates of cerebellum, blood, and liver following extraction of the
      radioactive steroid. The frontal brain was cut in sections for autoradiography.
      In the cerebellum of the mdr1a mutants, the amount of [3H]-dexamethasone relative
      to blood was about 5-fold higher than observed in the controls, whereas the ratio
      in blood vs. liver was not different. Using autoradiography, it was found that
      brain areas expressing the glucocorticoid receptor (GR) in high abundance, such
      as the hippocampal cell fields and the paraventricular nucleus (PVN), showed a 10
      fold increase in cell nuclear uptake of radiolabeled steroid. The amount of
      retained steroid increased toward levels observed in the pituitary, which
      contains a similar density of GRs. The [3H]-dexamethasone concentration in
      pituitary was not affected by mdr1a gene disruption. The GR messenger RNA
      expression pattern in hippocampus was not different between the wild types and
      mdr1a mutants, which rules out altered receptor expression as a cause of the
      enhanced dexamethasone uptake. In conclusion, the present study demonstrates that
      the brain is resistant to penetration by dexamethasone because of mdr1a activity
      at the level of the blood-brain barrier. The data support the concept of a
      pituitary site of action of dexamethasone in blockade of stress-induced ACTH
      release. Dexamethasone poorly substitutes for depletion of the endogenous
      glucocorticoid from the brain and therefore, in this tissue, may cause a
      condition resembling that of adrenalectomy.

PMID- 9528964
TI  - Mitogen-activated protein kinase kinase (MEK) activity is required for inhibition
      of skeletal muscle differentiation by insulin-like growth factor 1 or fibroblast
      growth factor 2.
AB  - Both insulin-like growth factor 1 (IGF-1) and fibroblast growth factor 2 (FGF-2)
      are key modulators of skeletal myoblast differentiation. The critical signaling
      pathways used by either IGF-1 or FGF-2 to inhibit differentiation have not been
      determined. In this study, we show that both IGF-1 and FGF-2 inhibit the
      differentiation of 23A2 myoblasts and that both stimulate signaling through
      mitogen-activated protein kinase (MAPK) kinase (MEK) to MAPK roughly 8-fold in
      23A2 myoblasts. We used the selective chemical inhibitor of MEK, PD 098059, to
      determine if signaling by MEK is required by IGF-1 or FGF-2 to inhibit
      differentiation. PD 098059 did not affect the ability of 23A2 myoblasts to
      differentiate. Addition of PD 098059 to the culture medium 10 min before the
      addition of IGF-1 or FGF-2 completely blocked the signal from MEK to MAPK and
      restored the ability of the 23A2 myoblasts to differentiate in the presence of
      either IGF-1 or FGF-2. The peak of signaling through MEK to MAPK in response to
      either IGF-1 or FGF-2 occurred within the first hour with maximal activation
      observed after 10 min. This signal remained elevated (at roughly 70% above basal)
      for at least 48 h. PD 098059 was added to the culture 60 min after IGF-1 or FGF-2
      to test whether this initial peak of signaling was sufficient for the inhibition
      of differentiation. The restoration of myogenic potential seen when cells were
      preincubated with PD 098059 was essentially identical to that seen when PD 098059
      was added to cultures after the initial peak of signaling from MEK to MAPK,
      suggesting that persistent signaling through MEK is required for the inhibition
      of differentiation by either IGF-1 or FGF-2.

PMID- 9528965
TI  - Angiotensin II activates mitogen-activated protein kinase via protein kinase C
      and Ras/Raf-1 kinase in bovine adrenal glomerulosa cells.
AB  - Angiotensin II (Ang II) stimulates growth and mitogenesis in bovine adrenal
      glomerulosa cells, but little is known about the signaling pathways that mediate
      these responses. An analysis of the growth-promoting pathways in cultured bovine
      adrenal glomerulosa cells revealed that Ang II, acting via the AT1 receptor,
      caused rapid but transient activation of mitogen-activated protein kinase (MAPK),
      with an ED50 of 10-50 pM. Although neither Ca2+ influx nor Ca2+ release from
      intracellular stores was sufficient to activate MAPK, Ca2+ appeared to play a
      permissive role in this response. A major component of Ang II-induced MAPK
      activation was insensitive to pertussis toxin (PTX), although a minor PTX
      sensitive component could not be excluded. Ang II also induced the rapid
      activation of ras and raf-1 kinase with time-courses that correlated with that of
      MAPK. Activation of protein kinase C (PKC) by phorbol 12-myristate 13-acetate was
      sufficient to activate both MAPK and raf-1 kinase. However, whereas PKC depletion
      had no effect on Ang II-induced raf-1 kinase activation, it attenuated Ang II
      induced MAPK activation. Ang II also stimulated a mobility shift of raf-1,
      reflecting hyperphosphorylation of the kinase. However, unlike its activation,
      raf-1 hyperphosphorylation was dependent on PKC and its time-course correlated
      not with activation, but rather with deactivation of the kinase. Taken together,
      these findings indicate that Ang II stimulates multiple pathways to MAPK
      activation via PKC and ras/raf-1 kinase in bovine adrenal glomerulosa cells.

PMID- 9528966
TI  - Regulation of glucocorticoid receptor and mineralocorticoid receptor messenger
      ribonucleic acids by selective agonists in the rat hippocampus.
AB  - Adrenal steroids can have prodigious effects on the structure, function, and
      survival of hippocampal neurons. In the rat hippocampus, the actions of adrenal
      steroids are mediated by two receptor types, the glucocorticoid receptor (GR) and
      the mineralocorticoid receptor (MR). Using in situ hybridization, we have
      examined the regulation of the messenger RNAs (mRNAs) encoding the glucocorticoid
      and mineralocorticoid receptors, by aldosterone, which acts selectively through
      MR, and by RU28362, which acts selectively through GR. Our results demonstrate
      that there is autoregulation of each receptor subtype, such that activation of GR
      regulates GR mRNA levels and MR activation regulates MR mRNA expression. In
      addition, there is evidence that aldosterone, acting through MR, can affect the
      expression of GR mRNA. The extent to which a specific agonist can produce a
      significant change in the expression of a particular steroid receptor mRNA varies
      between the different subfields of the hippocampus.

PMID- 9528967
TI  - Desensitization of the growth hormone-induced Janus kinase 2 (Jak 2)/signal
      transducer and activator of transcription 5 (Stat5)-signaling pathway requires
      protein synthesis and phospholipase C.
AB  - Signal transducers and activators of transcription (Stat) proteins are latent
      cytoplasmic transcription factors that are tyrosine phosphorylated by Janus
      kinases (Jak) in response to GH and other cytokines. GH activates Stat5 by a
      mechanism that involves tyrosine phosphorylation and nuclear translocation.
      However, the mechanisms that turn off the GH-activated Jak2/Stat5 pathway are
      unknown. Continuous exposure to GH of BRL-4 cells, a rat hepatoma cell line
      stably transfected with rat GH receptor, induces a rapid but transient activation
      of Jak2 and Stat5. GH-induced Stat5 DNA-binding activity was detected after 2 min
      and reached a maximum at 10 min. Continued exposure to GH resulted in a
      desensitization characterized by 1) a rapid decrease in Stat5 DNA-binding
      activity. The rate of decrease of activity was rapid up to 1 h of GH treatment,
      and the remaining activity declined slowly thereafter. The activity of Stat5
      present after 5 h is still higher than the control levels and almost 10-20% with
      respect to maximal activity at 10 min; and 2) the inability of further GH
      treatment to reinduce activation of Stat5. In contrast, with transient exposures
      of BRL-4 cells to GH, Stat5 DNA-binding activity could repeatedly be induced. GH
      induced Jak2 and Stat5 activities were independent of ongoing protein synthesis.
      However, Jak2 tyrosine phosphorylation and Stat5 DNA-binding activity were
      prolonged for at least 4 h in the presence of cycloheximide, which suggests that
      the maintenance of desensitization requires ongoing protein synthesis.
      Furthermore, inhibition of protein synthesis potentiated GH-induced
      transcriptional activity in BRL-4 cells transiently transfected with SPIGLE1CAT,
      a reporter plasmid activated by Stat5. GH-induced Jak2 and Stat5 activation were
      not affected by D609 or mepacrine, both inhibitors of phospholipase C. However,
      in the presence of D609 and mepacrine, GH maintained prolonged Jak2 and Stat5
      activation. Transactivation of SPIGLE1 by GH was potentiated by mepacrine and
      D609 but not by the phospholipase A2 inhibitor AACOCF3. Thus, a regulatory
      circuit of GH-induced transcription through the Jak2/Stat5-signaling pathway
      includes a prompt GH-induced activation of Jak2/Stat5 followed by a negative
      regulatory response; ongoing protein synthesis and intracellular signaling
      pathways, where phospholipase C activity is involved, play a critical role to
      desensitize the GH-activated Jak2/Stat5-signaling pathway.

PMID- 9528968
TI  - The effect of prostaglandin E2 on costochondral chondrocyte differentiation is
      mediated by cyclic adenosine 3',5'-monophosphate and protein kinase C.
AB  - Recent studies indicate that vitamin D metabolites exert rapid effects on growth
      plate chondrocytes via changes in PG production and protein kinase C (PKC)
      activity. This suggests that these two products of vitamin D action may be
      interrelated. To test this hypothesis, we examined the effect of PGE2 on rat
      costochondral resting zone and growth zone cartilage cells and determined whether
      the effects of PGE2 are mediated by changes in the level of cAMP and/or PKC
      activity, whether there is a relationship between cAMP production and PKC
      activity, and whether cell maturation-specific effects are involved. Confluent,
      fourth passage resting zone and growth zone cartilage cell cultures were
      incubated in DMEM containing 10% FBS, 50 microg/ml vitamin C, and 1% antibiotics.
      The PGE2 concentration was varied from 0.007-15 ng/ml. Low concentrations of PGE2
      caused a dose-dependent increase in cell number and [3H]thymidine incorporation
      and stimulated alkaline phosphatase specific activity. These effects were
      comparable in resting zone and growth zone cartilage cells at the same PGE2
      concentrations. At higher concentrations, PGE2 caused a general increase in the
      synthesis of collagenase-digestible protein and noncollagenase-digestible protein
      in resting zone cartilage cells and of collagenase-digestible protein in growth
      zone cartilage cells, resulting in a net increase in the percent collagen
      synthesis for both cell types. cAMP production was increased over the entire
      range of chondrocyte response. Prevention of cAMP metabolism with the protein
      kinase A inhibitors H-8 and H-89 blocked the PGE2-dependent inhibition of PKC in
      resting zone cartilage cells in a dose-dependent manner. H-8 alone had no effect
      on PKC in resting zone cartilage cells, but stimulated PKC activity in growth
      zone cartilage cells; H-89 alone stimulated PKC activity in resting zone
      cartilage cells. These results suggest that low levels of PGE2 promote
      differentiation, whereas high doses promote an anabolic response; PGE2 increases
      cAMP production and PKC activity in a cell maturation-dependent manner; PGE2
      exerts its effects via cAMP production and PKC activity; and regulation of PGE2
      dependent PKC is via cAMP.

PMID- 9528969
TI  - Differential use of signal transduction pathways in the gonadotropin-releasing
      hormone-mediated regulation of gonadotropin subunit gene expression.
AB  - The regulation of LH and FSH subunit gene expression is under the control of
      GnRH. Physiological changes in the frequency of pulsatile GnRH release from the
      hypothalamus result in differential stimulation of alpha-, LHbeta-, and FSHbeta
      gene expression. Previous studies indicate that the GnRH receptor couples to G
      proteins of the G(q/11) family, with phosphoinositide turnover and its resultant
      increase in intracellular calcium concentration and protein kinase C (PKC)
      activation, to stimulate secretion of LH and FSH. However, the molecular
      mechanisms by which GnRH mediates its transcriptional effects remain largely
      unknown. We used GH3 cells, constitutively expressing the rat GnRH receptor
      (GGH(3)-1' cells) and transiently transfected with a luciferase reporter gene
      controlled by either the alpha, LHbeta, or FSHbeta gene regulatory region
      (alphaLUC, LHbetaLUC, and FSHbetaLUC, respectively), to examine the roles of
      several signal transduction pathways in the GnRH-mediated stimulation of
      gonadotropin subunit gene expression. Activation of PKC by phorbol, 12-myristate,
      13-acetate resulted in an increase in the luciferase activity of all three
      gonadotropin subunit gene reporter constructs. Phorbol, 12-myristate, 13-acetate
      had a greater stimulatory effect, relative to the maximal stimulation with GnRH,
      for the beta-subunit genes than for the alpha-subunit gene. Depletion of PKC, or
      inhibition of PKC by GF109203X, demonstrated that PKC-dependent pathways play a
      larger role in the GnRH-mediated transcriptional control of the LHbeta- and
      FSHbeta-genes than the alpha-subunit gene. In contrast, an L-type calcium channel
      agonist, Bay K 8644, was able to stimulate alphaLUC but not LHbetaLUC or
      FSHbetaLUC. Nimodipine, an L-type calcium channel antagonist, had a larger
      inhibitory effect on the GnRH response of alphaLUC, relative to LHbetaLUC or
      FSHbetaLUC. We conclude from these results that the differential regulation of
      gonadotropin subunit gene expression by GnRH is caused, in part, by differential
      use of signal transduction pathways, activated upon GnRH binding.

PMID- 9528970
TI  - Distinct, tissue-specific regulation of vitamin D receptor in the intestine,
      kidney, and skin by dietary calcium and vitamin D.
AB  - We studied the effects of vitamin D deficiency and its correction by vitamin D or
      calcium-lactose supplementation on vitamin D receptor (VDR) expression in skin
      keratinocytes, kidney, and duodenum of adult rats. VDR messenger RNA (mRNA) was
      assayed by Northern blot, and VDR protein was determined immunocytochemically. In
      addition, four subpopulations of keratinocytes were isolated, characterized for
      their stages of differentiation, and analyzed for VDR expression. Vitamin D
      deficiency decreased VDR mRNA in all three tissues. Treatment with vitamin D or
      calcium-lactose reestablished the VDR mRNA content of the epidermis, but not that
      of the kidneys, and only the calcium-lactose diet increased duodenal VDR mRNA.
      The regulation of VDR mRNA in the epidermis was independent of cell
      differentiation, whereas VDR protein varied with differentiation. The VDR
      positive cells in the control rats were at early and advanced states of
      differentiation. The expression of VDR was decreased by vitamin D deficiency and
      returned to control values after vitamin D or calcium supplementation. Vitamin D
      treatment, but not calcium, induced VDR expression in the normally immature
      population. Vitamin D and calcium, therefore, have distinct, tissue-specific
      effects on VDR. In epidermis, the posttranscriptional regulation of VDR
      expression is linked to cell differentiation. Calcium may be a key factor for VDR
      transcription, whereas both vitamin D and calcium seem to contribute to its
      posttranscriptional regulation.

PMID- 9528971
TI  - Rat testicular N-cadherin: its complementary deoxyribonucleic acid cloning and
      regulation.
AB  - Using primer sets specific for mouse N-cadherin and rat testicular RNA for RT
      PCR, a full-length complementary DNA (cDNA) coding for rat testicular N-cadherin
      was isolated. The deduced amino acid sequence of rat N-cadherin yielded a 883
      amino acid polypeptide that displayed a 98.6% identity with the mouse homolog. N
      Cadherin was found to be expressed by Sertoli and germ cells in the rat testis by
      RT-PCR. Using Sertoli-germ cell cocultures, it was found that the N-cadherin
      expression increased with time in culture. To assess whether this is due to a
      soluble factor(s) released from germ cells that affects Sertoli cell N-cadherin
      expression, germ cell-conditioned media (GCCM) were fractionated by preparative
      anion-exchange HPLC, and the resulting fractions were divided into 14 pools. Pool
      4 was found to contain a factor(s) that induced a dose-dependent stimulation on
      Sertoli cell N-cadherin expression with a maximal stimulation at 2 microg
      protein/dish/4.5 x 10(6) Sertoli cells. At higher doses between 12 and 32 microg
      protein/dish, this pool relinquished its effect on Sertoli cell N-cadherin
      expression suggestive of a biphasic effect. This biphasic effect was confirmed
      using increasing doses of crude GCCM on Sertoli cell cultures. Since nonviable
      germ cells failed to stimulate Sertoli cell N-cadherin expression, it illustrates
      the observed stimulatory effect by GCCM is likely to be mediated via a soluble
      factor(s) releasing from viable germ cells. These results reveal the presence of
      a stimulatory factor(s) in GCCM that can modulate Sertoli cell N-cadherin
      expression in vitro. Since N-cadherin plays a crucial role in facilitating
      invasive capacity of metastatic tumor cells, the observation of germ cell
      released factor(s) in affecting Sertoli cell N-cadherin expression may suggest
      its possible role in facilitating germ cell migration during spermatogenesis.

PMID- 9528972
TI  - Regulation of glucose transport and c-fos and egr-1 expression in cells with
      mutated or endogenous growth hormone receptors.
AB  - To identify mechanisms by which GH receptors (GHR) mediate downstream events
      representative of growth and metabolic responses to GH, stimulation by GH of c
      fos and egr-1 expression and glucose transport activity were examined in Chinese
      hamster ovary (CHO) cells expressing mutated GHR. In CHO cells expressing wild
      type GHR(GHR(1-638)), GH stimulated the expression of c-fos and egr-1, and
      stimulated 2-deoxyglucose uptake, responses also mediated by endogenous GHR in
      3T3-F442A cells. Deletion of the proline-rich box 1 of GHR (GHR(deltaP))
      abrogated all of these responses to GH, indicating that box 1, a site of
      association of GHR with the tyrosine kinase JAK2, is crucial for these GH
      stimulated responses. As the C-terminal half of the cytoplasmic domain of GHR is
      required for GH-stimulated calcium flux and for stimulation of spi-2.1
      transcription, GHR lacking this sequence (GHR(1-454)) were examined. Not only did
      GHR(1-454) mediate stimulation of c-fos and egr-1 expression and 2-deoxyglucose
      uptake, but they also mediated GH-stimulated transcriptional activation via Elk
      1, a transcription factor associated with the c-fos Serum Response Element. Thus,
      the C-terminal half of the cytoplasmic domain of GHR is not required for GH
      stimulated c-fos transcription, suggesting that increased calcium is not required
      for GH-stimulated c-fos expression. In CHO cells lacking all but five N-terminal
      residues of the cytoplasmic domain (GHR(1-294)), GH did not induce c-fos or egr-1
      expression or stimulate 2-deoxyglucose uptake. Further, in 3T3-F442A fibroblasts
      with endogenous GHR, GH-stimulated c-fos expression and 2-deoxyglucose uptake
      were reduced by the tyrosine kinase inhibitors herbimycin A, staurosporine, and
      P11. Herbimycin A and staurosporine inhibit JAK2 and tyrosyl phosphorylation of
      all proteins stimulated by GH, whereas P11 inhibits the GH-dependent tyrosyl
      phosphorylation of only some proteins, including extracellular signal regulated
      kinases ERK1 and -2, but not JAK2. Taken together, these results implicate
      association of GHR with JAK2 and GH-stimulated tyrosyl phosphorylation of an
      additional cellular protein in GH-stimulated glucose transport and c-fos and egr
      1 expression. These studies also indicate that, in contrast to spi-2.1, the N
      terminal half of the cytoplasmic domain of GHR is sufficient to mediate
      stimulation of c-fos and egr-1 expression and Elk-1 activation, supporting
      multiple mechanisms for GH signaling to the nucleus.

PMID- 9528974
TI  - Testicular leukemia inhibitory factor (LIF) and LIF receptor mediate
      phosphorylation of signal transducers and activators of transcription (STAT)-3
      and STAT-1 and induce c-fos transcription and activator protein-1 activation in
      rat Sertoli but not germ cells.
AB  - Increasing amounts of evidence suggest noninflammatory roles for growth factor
      and cytokines in development and differentiation. Leukemia inhibitory factor
      (LIF) belongs to a gp130 pleiotropic family of growth factors that has recently
      been shown to enhance the survival of rat testicular gonocytes and Sertoli cells.
      In this study, we show the expression of gp130 and LIF messenger RNAs (mRNAs) in
      the somatic (the Sertoli and Leydig cells) and specific germ cells
      (spermatogonia, pachytene, round, and elongated spermatids) of rodent testis,
      suggestive of cell-specific LIF-mediated functions. LIF receptor mRNA was
      demonstrated in rat somatic cells, rat elongating spermatids, and all of the
      mouse germ cells. In addition, we characterized the effects of LIF on the signal
      transducers and activators of transcription (STAT)-3 and STAT-1, c-fos gene
      expression, and activator protein-1 regulation in primary rat Sertoli cells.
      Electrophoretic mobility shift assay and Western blot analysis demonstrated that
      LIF translocates STAT-3 (and to a lesser extent STAT-1) transcription factor(s)
      to the nucleus within 2 min of exposure in a tyrosine but not serine/threonine
      phosphorylation-dependent pathway. Quantitative solution hybridization analysis
      revealed a transient increase in c-fos mRNA levels by 20-fold following 30-45 min
      of LIF treatment, an effect that was inhibited by the tyrosine, as well as
      serine/threonine kinase inhibitors, genistein, and H7. Subsequently, LIF
      treatment of the Sertoli cells increased nuclear activator protein-1 binding
      proteins at 2 h after its addition, an effect that was also sensitive to
      genistein and H7 pretreatments. In contrast, LIF treatment of primary rat germ
      cells did not alter c-fos mRNA levels. Species specificity in the expression of
      LIF receptor as well as ligand binding may play a role in LIF signaling in these
      germ cells. Thus, using a primary Sertoli cell model, we demonstrated that the
      testicular LIF signaling pathway is contingent on the phosphorylation of latent
      transcription factors. Our data are consistent with LIF-mediated signaling events
      involving both somatic and germ cells during spermatogenesis.

PMID- 9528973
TI  - Lactogenic hormone-inducible phosphorylation and gamma-activated site-binding
      activities of Stat5b in primary rat Leydig cells and MA-10 mouse Leydig tumor
      cells.
AB  - The signal transducer and activator of transcription Stat5b has been implicated
      in signal transduction pathways for a number of cytokines and growth factors,
      including GH and PRL. Although these lactogenic hormones have the potential to
      enhance gonadotropin-induced steroidogenesis, the role of GH and PRL in the
      testis has long been and remains the subject of controversy. In this report we
      provide, to our knowledge, the first evidence of Stat5b protein expression in the
      testis and characterize the activation of Stat5b by these lactogenic hormones in
      primary rat progenitor, immature and adult Leydig cells, and mouse MA-10 Leydig
      tumor cells. In MA-10 cells, both GH and PRL mediate tyrosine phosphorylation of
      Janus kinase (JAK) 2 and Stat5b and induce DNA-binding activity of Stat5b. GH
      enhances both PIE (PRL-inducible element) and Fc gammaRI gamma-activated sites
      (GAS), but PRL modulates only PIE GAS. In primary Leydig cells isolated from 18
      day-old rats, GH, but not PRL, activates cytoplasmic Stat5b and induces the
      binding of translocated nuclear Stat5b to GAS elements. Although Stat5b protein
      is expressed in both Percoll- and elutriator-purified adult rat Leydig cells,
      neither GH nor PRL treatment results in Stat5b-DNA binding. Our studies indicate
      that the MA-10 cell has the capacity to bind both GH and PRL and provides a
      useful model system with which to study the distinct testicular roles of these
      hormones. Moreover, our findings suggest that progenitor and immature Leydig
      cells are functional targets for GH in the immature rat, suggestive of a role for
      GH-Stat5b in testicular development. Our data indicate that lactogenic hormone
      inducible transcriptional activation may target distinct gene expression in a
      signaling cascade(s) involving Stat5b but also imply coordinate control by
      multiple Leydig cell factors.

PMID- 9528975
TI  - The formation of thyrotropin receptor (TSHR) antibodies in a Graves' animal model
      requires the N-terminal segment of the TSHR extracellular domain.
AB  - Immunization of AKR/N mice with murine fibroblasts, transfected with the TSH
      receptor (TSHR) and a murine major histocompatibility complex class II molecule
      having the same H-2k haplotype (but not either alone), induces immune thyroid
      disease with the humoral and histological features of human Graves', including
      the presence of two different TSHR antibodies (TSHRAbs): stimulating TSHRAbs,
      which cause hyperthyroidism; and TSH-binding-inhibiting immunoglobulins. The
      primary functional epitope for both types of antibodies in Graves' patients is on
      the N-terminal portion of the extracellular domain of the TSHR, residues 25 to
      165; most require residues 90-165 to express TSHRAb activity, as evidenced in
      studies using chimeras of the TSHR and lutropin-choriogonadotropin receptor (LH
      CGR). To evaluate the role of this region of the TSHR in the formation of Graves'
      TSHRAbs, we immunized AKR/N mice with fibroblasts transfected with three human
      TSHR chimeras with residues 9-165 (Mc1+2), 90-165 (Mc2), or 261-370 (Mc4)
      substituted by equivalent residues of the rat LH-CGR. Mice immunized with the
      Mc1+2 and Mc2 chimeras, with the N-terminal portion of the extracellular domain
      of the TSHR substituted by LH-CGR residues, did not develop TSHRAbs. Mice
      immunized with the Mc4 chimera, having a major portion of the C-terminal portion
      of the extracellular domain of the TSHR replaced by comparable LH-CGR residues,
      can develop TSHRAbs. The results suggest that the N-terminal segment of the TSHR
      extracellular domain is not only a critical functional epitope for Graves'
      TSHRAbs, but it is important also in their formation in a mouse model of Graves'
      disease.

PMID- 9528976
TI  - Growth hormone and mild exercise in combination markedly enhance cortical bone
      formation and strength in old rats.
AB  - The effects of a combination of mild exercise and GH injections on bone were
      studied in old female rats. Biosynthetic human GH, 2.7 mg/kg/day, was injected
      s.c. for 73 days. Exercised rats ran 8 m/min on a treadmill for 1 h/day. All rats
      (age 21 months old) were labeled with a tetracycline injection 56 days and a
      calcein injection 11 days before killing. The GH injections resulted in an 11
      fold increase in femoral middiaphyseal bone formation rate and a 12% increase in
      cross-sectional area compared with the saline-injected group. The mild exercise
      doubled the mineralizing surface but did not influence the bone formation rate
      significantly. The combination of GH injections plus exercise, however, resulted
      in a further increase of 39% in bone formation rate, primarily at the
      anterolateral aspects, and an increase of 5% in cross-sectional area compared
      with the group injected with GH only. The femur ultimate breaking load was
      increased by 37% and the stiffness by 42% in the group injected with GH compared
      with the saline-injected group. Exercise alone did not influence the femur
      mechanical properties. The combination of GH injections plus exercise induced a
      4% further increase in ultimate breaking load and 7% further increase in
      stiffness compared with the group injected with GH alone. The GH injections
      induced a 117% increase in serum insulin-like growth factor I. The GH-insulin
      like growth factor I axis stimulates recruitment of osteoblast precursor cells,
      resulting in increased bone formation at the periosteal surface. GH injections
      and mild excercise in combination modulate and increase further the formation and
      strength of cortical bone in old female rats.

PMID- 9528977
TI  - The antagonists RU486 and ZK98299 stimulate progesterone receptor binding to
      deoxyribonucleic acid in vitro and in vivo, but have distinct effects on receptor
      conformation.
AB  - Three types of transfection experiments were used to detect the abilities of
      different classes of antagonists to stimulate binding of progesterone receptor
      (PR) to progesterone response elements (PRE) in intact mammalian cells. These
      included a promoter interference assay, in which PR binding to PREs positioned
      between the TATA box and the start of transcription is detected as a reduction of
      expression of a constitutively active reporter gene, competition of PR antagonist
      and glucocorticoid receptor agonist for a common glucocorticoid response
      element/PRE-controlled reporter construct, and activation of a chimeric receptor
      (PR-VP16) containing the constitutive trans-activation domain derived from the
      VP16 protein of herpes simplex virus. By each approach, all antagonists tested
      were equally effective in stimulating PR binding to PREs in the cell. This
      included previously designated type I (ZK98299) and type II (RU486, ZK98734, and
      ZK112993) 11beta-aryl substituted steroid analogs. Stimulation of PR binding to
      PREs in the cell by ZK98299 was of interest because this antagonist has been
      reported to lack the ability to stimulate PR-DNA binding in vitro by
      electrophoretic gel mobility shift assay compared with RU486, which promotes
      efficient binding of PR to PREs. To clarify the apparent discrepancy between
      intact cell and in vitro results with ZK98299, we altered electrophoretic gel
      mobility shift assay conditions to allow detection of less stable DNA complexes.
      Under these conditions, ZK98299 induced the formation of specific PR-PRE
      complexes. Further analysis of the ZK98299-induced DNA complexes revealed that
      they exhibited an electrophoretic mobility different from that of the complexes
      induced by RU486, and the off-rate of PR from DNA was faster than that of the PR
      bound to agonist. This suggests that ZK98299 promotes a conformational change
      within PR distinct from that induced by RU486. The present results are consistent
      with the conclusions that ZK98299 stimulates PR binding to target DNA sequences
      and that ZK98299 and RU486 represent two mechanistic classes of antagonists based
      on inducing different conformational changes in PR.

PMID- 9528978
TI  - Regulation of endothelial production of C-type natriuretic peptide by interaction
      between endothelial cells and macrophages.
AB  - We demonstrated endothelial production of C-type natriuretic peptide (CNP), the
      third member of the natriuretic peptide family, and its regulation by cytokines,
      including tumor necrosis factor-alpha (TNF alpha). We thus proposed that CNP can
      control vascular tone and growth as an endothelium-derived relaxing peptide. We
      also revealed the marked elevation of plasma CNP concentration in patients with
      septic shock, in which TNF alpha plays a significant part. As the interaction
      between endothelial cells (EC) and monocytes-macrophages plays a pivotal role in
      the pathogenesis of atherosclerosis, we investigated the effect of coculture of
      EC and macrophages on endothelial production of CNP. We used a human monocytic
      leukemia cell line, THP-1, which differentiates into macrophages when treated
      with phorbol 12-myristate 13-acetate. The coculture of EC and THP-1-derived
      macrophages enhanced CNP secretion by more than 10-fold compared with the single
      culture of EC or the coculture of EC and THP-1 without phorbol 12-myristate 13
      acetate treatment. Prevention of direct contact between EC and THP-1-derived
      macrophages did not attenuate the increase in CNP secretion. Northern blotting
      revealed the augmentation of CNP messenger RNA expression in EC in the coculture.
      We detected TNF alpha in the conditioned medium from the coculture of EC and THP
      1-derived macrophages. Furthermore, anti-TNF alpha antibody inhibited the
      stimulation of CNP secretion in the coculture. CNP at a concentration of 1 nM did
      not stimulate cGMP production in EC or THP-1-derived macrophages, but it elevated
      cGMP production significantly in vascular smooth muscle cells. These results
      indicate that endothelial production of CNP is stimulated mainly by TNF alpha
      released from THP-1-derived macrophages in the coculture. Endothelial CNP at the
      enhanced level may be one of the vascular mediators to regulate local vascular
      tone and growth through cGMP production by vascular smooth muscle cells,
      suggesting the potential significance of endothelial CNP in atherosclerosis.

PMID- 9528979
TI  - Blockade of growth hormone receptor shedding by a metalloprotease inhibitor.
AB  - GH, an important growth-promoting and metabolic hormone, exerts its biological
      effects by interacting with cell surface GH receptors (GHRs). The GHR is a single
      membrane-spanning protein that binds GH via its extracellular domain. The high
      affinity GH-binding protein (GHBP), which corresponds to a soluble form of the
      GHR extracellular domain, carries a substantial fraction of the GH in the
      circulation of various species and probably has a role in modulation of the
      hormone's bioavailability. Although in rodents, it is believed that the GHBP is
      largely derived by translation of an alternatively spliced GHR messenger RNA, in
      humans and rabbits, proteolytic cleavage of the membrane-anchored receptor
      releases the GHR extracellular domain, which is believed to thereby become the
      GHBP. In this study, we used human IM-9 lymphocytes and GHR antibodies to study
      this proteolytic shedding of the GHBP. As determined by immunoblotting with anti
      GHR cytoplasmic domain serum, addition of phorbol 12-myristate 13-acetate (PMA; 1
      microg/ml) to serum-starved cells led to rapid loss (roughly 60% decline after 1
      h; t(1/2) = approximately 5 min) of mature GHRs (115-140 kDa) from either total
      cell or detergent-soluble extracts. Loss of full-length GHRs was accompanied by
      accumulation of four proteins (65-68 kDa), each reactive with the cytoplasmically
      directed antiserum. The pattern of appearance of these GHR ctyoplasmic domain
      proteins, the electrophoretic and immunological characteristics of which are
      similar to those of a recombinant rabbit GHR mutant that lacks the extracellular
      domain, was such that progressively faster migrating forms were evident between 5
      60 min of PMA exposure. Treatment with N-ethylmaleimide (NEM; 5 mM), an agent
      known to cause GHBP shedding from IM-9 cells, promoted a similar rapid loss of
      full-length GHRs and an accumulation of GHR cytoplasmic domain remnant proteins.
      PMA-induced, but not NEM-induced, GHR proteolysis was blocked by the protein
      kinase C inhibitor, GF109203X. Both PMA- and NEM-induced receptor proteolysis
      were, however, inhibited by the metalloprotease inhibitor, Immunex Compound 3
      (minimum effective concentration, 10 microM). Notably, PMA and NEM also promoted
      shedding of GHBP into the conditioned medium of the cells, as determined by a
      chromatographic [125I]human GH binding assay; this GHBP shedding was also
      inhibited by Immunex Compound 3. These results strongly implicate a member(s) of
      the metalloprotease family as a potential GHBP-generating enzyme.

PMID- 9528981
TI  - Multivalent cations depress ligand binding to cell-associated insulin-like growth
      factor binding protein-5 on human glioblastoma cells.
AB  - The current studies quantified the effect of the multivalent cations zinc,
      cadmium, lanthanum, chromium, and gold (Zn2+, Cd2+, La3+, Cr3+, and Au3+) on
      [125I]-insulin-like growth factor ([125I]-IGF) binding to T98G human glioblastoma
      cells. The major binding site for the IGFs on T98G cells is IGF binding protein-5
      (IGFBP-5), as determined by affinity labeling. Competitive binding studies, using
      either [125I]-IGF-I or [125I]-IGF-II, indicated that La3+ and Cr3+ did not affect
      [125I]-IGF-I or [125I]-IGF-II binding to cell-associated IGFBP-5. Zn2+, Au3+, and
      Cd2+ depressed binding of both [125I]-IGF-I and [125I]-IGF-II. [125I]-IGF-I and
      [125I]-IGF-II binding resulted in nonlinear concave-down Scatchard plots,
      indicating the presence of high- and low-affinity equilibrium constant of
      association (Ka) sites. Assuming a preexisting asymmetric model with independent
      high (KaHi) and low (KaLo) sites; Zn2+, Cd2+, and Au3+ eliminated KaHi and Zn2+,
      and Au3+ lowered KaLo, compared with control values. The same results were found,
      independent of whether [125I]-IGF-I or [125I]-IGF-II was used. Similarly,
      assuming a ligand-induced model of negative cooperativity, all three cations
      eliminated the initial affinity for the high affinity sites (Ka), whereas Zn2+
      and Au2+ reduced the final affinity for the low affinity sites (Kf). Dose
      response studies indicated that Zn2+, Au3+, and Cd2+ depressed binding with half
      maximal activities of approximately 20 microM, 14-60 microM, and 50-65 microM,
      respectively. Zn2+, Au3+, and Cd2+ bind to similar sites on proteins (a zinc
      binding motif), indicating similar mechanisms of action. A zinc-binding motif is
      present within the IGFBPs but not the IGFs. We demonstrate, for the first time,
      that multivalent cations have the potential to modulate IGF activity by
      decreasing the amount of IGF bound to cell-associated IGFBP-5.

PMID- 9528980
TI  - Establishment and characterization of a simian virus 40-transformed temperature
      sensitive rat luteal cell line.
AB  - The primary culture of rat luteal cells and their long-term maintenance have been
      difficult. Low cellular yields have limited the possibility for the study of gene
      regulation in luteal cells. The goal of this study was to develop a cell line to
      serve as a model by which to study the expression and regulation of various genes
      specific to luteal cells. We attempted to develop a luteal cell line by
      transformation of large luteal cells through infection with a temperature
      sensitive simian virus (SV-40 tsA209) mutant that has a temperature-sensitive
      mutation required for the maintenance of cell transformation. We report here the
      successful establishment of such a cell line, designated GG-CL cells. Large
      luteal cells were purified to homogeneity by flow cytometry from corpora lutea of
      day 14 pregnant rats, cultured for 24 h, and then infected with the SV-40 tsA209
      mutant virus. Transformed cells were maintained at the permissive temperature (33
      C) until colonies were identified. Several colonies of transformed cells were
      isolated and passaged. They multiplied at 33 C and formed multilayers. At the
      nonpermissive temperature (40 C), cells reverted to the normal differentiated
      phenotype similar to the primary luteal cells in culture. To determine whether GG
      CL cells express the genes found in normal luteal cells, messenger RNA (mRNA)
      expression was examined by either Northern analysis or RT-PCR with primers
      specific to each mRNA. GG-CL cells were found to express receptors for
      interleukin-6 and glucocorticoid, as well as the newly discovered estrogen
      receptor-beta (ER-beta) and the orphan nuclear receptor nur 77. No receptors for
      ER-alpha, progesterone, LH, or PRL could be detected. This cell line also
      expressed 20alpha-hydroxysteroid dehydrogenase (20alpha-HSD), but not cholesterol
      side-chain cleavage cytochrome P450 (P450scc), 3beta-hydroxysteroid
      dehydrogenase, or aromatase cytochrome P450 (P450arom). Although the cells did
      not express the PRL receptor, they did express Janus kinase (JAK2) and signal
      transducers and activators of transcription (Stat5b), and, when transfected with
      the PRL receptor, they responded to PRL with a marked inhibition in 20alpha-HSD
      mRNA expression. In addition, estradiol enhanced ER-beta expression in a dose
      dependent manner whereas cAMP stimulation caused a marked and rapid increase in
      the expression of the orphan receptor nur 77. In summary, a temperature-sensitive
      cell line was successfully established from the large luteal cells of rat corpora
      lutea. These cells express key genes encoding enzymes and receptors inherent to
      this defined luteal cell population and respond to stimulation by PRL, estradiol,
      and cAMP.

PMID- 9528982
TI  - Conditionally immortalized murine bone marrow stromal cells mediate parathyroid
      hormone-dependent osteoclastogenesis in vitro.
AB  - PTH recruits and activates osteoclasts to cause bone resorption. These actions of
      PTH are thought to be mediated indirectly via type 1 PTH/PTH-related peptide
      receptors (PTH1Rs) expressed by adjacent marrow stromal or osteoblastic cells,
      although some evidence suggests that PTH may act directly on early hematopoietic
      osteoclast progenitors. We have established clonal, conditionally immortalized,
      PTH-responsive, bone marrow stromal cell lines from mice that harbor both a
      transgene encoding a temperature-sensitive mutant of the simian virus 40 large T
      antigen and deletion of a single allele of the PTH1R gene. Of 60 stromal cell
      lines isolated, 45 expressed functional PTH1Rs. During coculture with normal
      murine spleen cells, 5 of 42 such cell lines could support formation of tartrate
      resistant acid phosphatase-positive, multinucleated cells (TRAP+ MNCs) in
      response to 1,25-dihydroxyvitamin D3, but only 2 of these did so in response to
      PTH. One of these, MS1 cells, expressed numerous cytokines and proteins
      characteristic of the osteogenic lineage and showed increased production of
      interleukin-6 in response to PTH. MS1 cells supported dose-dependent induction by
      rat (r) PTH-(1-34) (0.1-100 nM) of TRAP+ MNCs that expressed calcitonin receptors
      and formed resorption lacunae on dentine slices. This effect of PTH, which
      required cell to cell contact between MS1 and spleen cells, was mimicked by
      coadministration of cAMP analog and phorbol ester but only partially by either
      agent alone. The carboxyl-terminal fragment rPTH-(53-84) also induced osteoclast
      like cell formation, but the maximal effect was only 30% as great as that of rPTH
      (1-34). Importantly, rPTH-(1-34) induced TRAP+ MNC formation even when PTH1R-/-
      osteoclast progenitors (from fetal liver of mice homozygous for ablation of the
      PTH1R gene) were cocultured with MS1 cells. We conclude that activation of PTH1Rs
      on cells of the osteoclast lineage is not required for PTH-(1-34)-induced
      osteoclast formation in the presence of appropriate PTH-responsive marrow stromal
      cells. MS1 cells provide a useful model for further study of PTH regulation of
      osteoclastogenesis.

PMID- 9528983
TI  - Growth hormone stimulation of the mitogen-activated protein kinase pathway is
      cell type specific.
AB  - The GH receptor is a member of the cytokine receptor superfamily. Studies in the
      3T3-F442A mouse preadipocyte have shown that GH activates the Janus kinase
      (JAK2), the signal transducers and activators of transcription (STAT1, -3, and 
      5), and mitogen-activated protein (MAP) kinase. Our previous studies in the human
      IM-9 lymphocyte have shown that GH activates JAK2 and only STAT5 (not STAT1 or 
      3). In the studies presented here, we have investigated activation of the MAP
      kinase (MAPK) pathway in the IM-9 lymphocyte. Western blotting with
      antiphosphotyrosine-, anti-MAPK-, and anti-phospho-MAPK-specific antibodies as
      well in vitro kinase assays using a synthetic peptide substrate demonstrate that
      although GH (200 ng/ml) activates MAPK in 3T3-F442A cells (at 5 and 10 min of
      treatment), it does not activate MAPK in IM-9 lymphocytes at time points ranging
      from 5-60 min. Nevertheless, the phorbol ester phorbol 12-myristate 13-acetate
      (50 ng/ml) does activate MAPK in the IM-9 cell, and immunoprecipitation with
      specific antibodies indicates that this activation occurs through c-Raf-1.
      Although the 52- and 66-kDa forms of the adapter protein Shc are tyrosine
      phosphorylated in response to GH treatment in 3T3-F442A cells, we demonstrate
      that the predominant forms in IM-9 cells are the 52- and 46-kDa forms, and
      neither is tyrosine phosphorylated in response to GH. These studies further
      elucidate the differential signaling by GH in two cell types.

PMID- 9528984
TI  - Expression of retinoic acid receptor-beta sensitizes prostate cancer cells to
      growth inhibition mediated by combinations of retinoids and a 19-nor hexafluoride
      vitamin D3 analog.
AB  - Retinoids and analogs of vitamin D3 may achieve greater in vivo applications if
      the toxic side effects encountered at pharmacologically active doses could be
      alleviated. These seco-steroid hormones often act in concert, and therefore, we
      attempted to dissect these interactions by isolating combinations of receptor
      selective retinoids and a potent vitamin D3 analog [1alpha,25(OH)2-16ene-23-yne
      26,27,F6-19nor-D3, code name LH] that were potent inhibitors of prostate cancer
      cell growth at low, physiologically safer doses. Using a panel of prostate cancer
      cell lines representing progressively more transformed phenotypes, we found that
      the LNCaP cell line (least transformed) was either additively or synergistically
      inhibited in its clonal growth by LH and various naturally occurring and receptor
      selective retinoids, the most potent combination being with a retinoic acid
      receptor (RAR)betagamma-selective retinoid (SR11262). The effect was not found
      with either PC-3 (intermediate transformation) or DU-145 (most transformed). We
      also undertook RT-PCR to examine the subtypes of RARs present, and we found that
      PC-3 and DU-145 did not express RARbeta. Stable expression of RARbeta into the
      RARbeta-negative PC-3 cells resulted in increased sensitivity to SR11262 and LH
      proportional to the amount of RARbeta expressed. This study indicates that
      RARbeta may play an important role in synergistically controlling cell
      proliferation, and expression is lost with increased prostate cancer cell
      transformation. Simultaneous administration of a potent vitamin D3 analog and
      receptor-selective retinoids may have therapeutic potential for the treatment of
      androgen-dependent and -independent prostate cancer.

PMID- 9528985
TI  - Estrogen-induced c-fos protooncogene expression in MCF-7 human breast cancer
      cells: role of estrogen receptor Sp1 complex formation.
AB  - 17Beta-estradiol (E2) induces c-fos protooncogene expression in MCF-7 human
      breast cancer cells, and previous studies in HeLa cells identified an imperfect
      palindromic estrogen-responsive element (-1212 to -1200) that was required for
      trans-activation. In contrast, the estrogen-responsive element was not required
      for E2 responsiveness in MCF-7 cells, and using a series of constructs containing
      wild-type (pF1) and mutant 5'-flanking sequences (-1220 to -1155) from the c-fos
      protooncogene promoter in transient transfection assays, it was shown that a GC
      rich motif (5'-GGGGCGTGG) containing an imperfect Sp1-binding site was required
      for hormone-induced activity. This sequence also bound Sp1 protein in gel
      mobility shift assays, and coincubation with the estrogen receptor (ER) enhanced
      Sp1-DNA binding. E2 and 4'-hydroxytamoxifen, but not ICI 164,384, induced
      reporter gene activity in cells transiently transfected with pF1. E2 induced
      reporter gene activity in MDA-MB-231 breast cancer cells transiently
      cotransfected with pF1 and wild-type ER or variant ER in which the DNA-binding
      domain was deleted (HE11); plasmids expressing N-terminal or C-terminal domains
      of the ER containing activator function-1 or -2, respectively, were inactive in
      these assays. In contrast, only wild-type ER mediated 4'-hydroxytamoxifen-induced
      activity. Induction of c-fos protooncogene expression by E2 in MCF-7 cells is
      dependent on the formation of a transcriptionally active ER/Sp1 complex that
      binds to a GC-rich enhancer element.

PMID- 9528986
TI  - Differential effects of cyclic adenosine 3',5'-monophosphate on p70 ribosomal S6
      kinase.
AB  - cAMP exerts differential effects on mitogenic signaling pathways. In many cells,
      cAMP inhibits growth factor-stimulated MAPK activity and proliferation. In
      others, cAMP promotes growth. TSH stimulates proliferation through elevations in
      cAMP in thyroid follicular cells. This mitogenic pathway is dependent upon both
      protein kinase A and Ras, but not upon Raf-1, mitogen-activated protein kinase
      kinase, or mitogen-activated protein kinase. We report that TSH, acting through
      cAMP, activates pp70s6k and that this activity is required for TSH-stimulated DNA
      synthesis. A similar role for pp70s6k in cAMP-mediated mitogenesis was observed
      in secondary rat Schwann cells and in Swiss3T3 fibroblasts, two additional cell
      types that respond to cAMP with growth. In contrast, cAMP elevation did not
      activate pp70s6k in NIH3T3 or REF52 fibroblasts, cells in which cAMP fails to
      stimulate proliferation. Together, these results suggest that pp70s6k plays an
      important and general role in cAMP-mediated proliferation.

PMID- 9528988
TI  - Neonatal immunization against gonadotropin-releasing hormone (GnRH) results in
      diminished GnRH secretion in adulthood.
AB  - The effects of neonatal immunization against GnRH were studied in sheep after
      they had reached adulthood (3-4 yr) and the antibody titers had fallen to
      undetectable levels. The immunized animals had small gonads, and the females did
      not have large follicles (>3 mm) or corpora lutea in their ovaries. Compared with
      controls, the immunized animals had low or nondetectable levels of LH and FSH in
      peripheral plasma, and the immunized animals generally failed to respond to a
      single i.v. GnRH challenge. After ovariectomy, the control ewes, but not the
      immunized ewes, showed an elevation in plasma LH and FSH levels. The sampling of
      hypophysial portal blood, with a newly described method, showed that the
      secretion of GnRH was reduced in the immunized animals, but the amount of GnRH in
      the median eminence was similar in the control and immunized ewes. The pituitary
      content of LH and FSH was reduced in the immunized ewes as was messenger RNA for
      the gonadotropin subunits and the GnRH receptor. These data indicate that
      neonatal immunization does not affect the synthesis of GnRH in adulthood but
      reduces the secretion of GnRH, causing long-term sterility in these animals.

PMID- 9528987
TI  - Multiple transcripts encoded by the thyroid-specific enhancer-binding protein
      (T/EBP)/thyroid-specific transcription factor-1 (TTF-1) gene: evidence of
      autoregulation.
AB  - Multiple transcripts derived from the gene encoding rat thyroid-specific enhancer
      binding protein (T/EBP)/thyroid-specific transcription factor-1 (TTIF-1) were
      identified by complementary DNA cloning and sequencing, and Northern blotting
      analyses. Six different types of complementary DNAs were identified that differ
      at their 5' noncoding regions; four contain an intron of different lengths,
      whereas the other two possess no intron. Ribonuclease protection analyses
      revealed that multiple promoters are scattered throughout the upstream region,
      and the usage of these different promoters together with alternative splicing
      leads to a family of T/EBP messenger RNA (mRNA) species. A similar pattern of
      expression was also found in the human T/EBP gene expressed in a lung carcinoma
      cell line. Longer T/EBP mRNAs are more abundant in rat FRTL-5 thyroid cells
      maintained in the absence of TSH (-TSH) than in cells maintained in the presence
      of TSH (+TSH). Transfection analyses using the rat T/EBP gene DNA upstream of the
      ATG initiation codon connected to the luciferase reporter plasmid showed a
      similar relative activity profile between -TSH and +TSH culture conditions,
      suggesting that the abundance of longer mRNAs in -TSH conditions may not directly
      correlate with differences in promoter activities. Rather, TSH status might have
      a role in maintaining the physiological state of the cells. The upstream DNA of
      the rat and human T/EBP genes share a cluster of high and low sequence
      similarities, and both possess respectively 24 and 18 putative T/EBP-binding
      sites throughout. Cotransfection analyses of the T/EBP promoter-reporter
      constructs with a T/EBP expression vector into human HepG2 cells, which do not
      express T/EBP, suggested that autoregulation may be involved in controlling both
      rat and human T/EBP gene expression.

PMID- 9528989
TI  - Presence of salmon gonadotropin-releasing hormone (GnRH) and compounds with GnRH
      like activity in the ovary of goldfish.
AB  - The presence of ovarian GnRH and/or compounds with GnRH-like activity was
      investigated in the goldfish ovary. Goldfish ovary was extracted using an
      acetone/HCl/ether mixture and was purified by Waters C-18 Sep-Pak columns
      (ovarian extract). The goldfish ovarian extract was found to 1) stimulate
      gonadotropin release and subunit messenger RNA production in the goldfish
      pituitary that was inhibited by a GnRH antagonist; 2) stimulate germinal vesicle
      breakdown in the prophase-I arrested follicle-enclosed goldfish oocytes in vitro,
      which was inhibited by a GnRH antagonist; 3) immunoreact with various GnRH
      antisera; and 4) bind to GnRH receptors in the goldfish pituitary and ovary as
      well as rat pituitary. Further purification with HPLC revealed the presence of
      two compounds with GnRH-like activity. One with identical chromatographic
      characteristics, amino acid composition, and primary structure to that of the
      salmon GnRH (sGnRH), and the other a novel compound with GnRH-like activity.

PMID- 9528990
TI  - Inhibition of adenylyl cyclase by caveolin peptides.
AB  - Caveolae and their principal component caveolin have been implicated in playing a
      major role in G protein-mediated transmembrane signaling. We examined whether
      caveolin interacts with adenylyl cyclase, an effector of G protein signaling,
      using a 20-mer peptide derived from the N-terminus scaffolding domain of caveolin
      1. When tissue adenylyl cyclases were examined, cardiac adenylyl cyclase was
      inhibited more potently than other tissue adenylyl cyclases. The caveolin-1
      peptide inhibited type V, as well as type III adenylyl cyclase, overexpressed in
      insect cells, whereas the same peptide had no effect on type II. The caveolin-3
      scaffolding domain peptide similarly inhibited type V adenylyl cyclase. In
      contrast, peptides derived from the caveolin-2 scaffolding domain and a caveolin
      1 nonscaffolding domain had no effect. Kinetic studies showed that the caveolin-1
      peptide decreased the maximal rate (Vmax) value of type V without changing the
      Michaelis constant (Km) value for the substrate ATP. Studies with various
      truncations and point mutations of this peptide revealed that a minimum of 16
      amino acid residues and intact aromatic residues are important for the inhibitory
      effect. The potency of inhibition was greater when adenylyl cyclase was in
      stimulated condition vs. basal condition. Thus, caveolin may be another cellular
      component that regulates adenylyl cyclase catalytic activity. Our results also
      suggest that the caveolin peptide may be used as an isoform-selective inhibitor
      of adenylyl cyclase.

PMID- 9528991
TI  - Inhibitory effect of glucocorticoid for osteoblast apoptosis induced by activated
      peripheral blood mononuclear cells.
AB  - Recent studies suggest a protective effect of glucocorticoid against progression
      of bone erosion and periarticular osteoporosis in patients with rheumatoid
      arthritis (RA), although this steroid hormone itself is believed to increase bone
      loss. To understand the antagonistic effect of glucocorticoid for osteopenic
      process in RA patients, we examined the effect of dexamethasone on Fas-mediated
      apoptosis of cultured human osteoblasts induced by either anti-Fas IgM or
      activated peripheral blood mononuclear cells (PBMC). Human osteoblastic cell line
      MG63 and primary osteoblast-like cells obtained from biopsy specimens were used
      in this study. PBMC isolated from healthy donors were cultured with or without
      recombinant interleukin-2 (rIL-2) followed by 12-O-tetradecanoyl-phorbol 13
      acetate (PMA) with ionomycin in the presence or absence of dexamethasone. Fas was
      functionally expressed on MG63 and primary osteoblast-like cells, and treatment
      of these cells with dexamethasone affected neither Fas expression nor anti-Fas
      IgM-induced apoptosis. Activated PBMC expressing membrane-type Fas ligand (mFasL)
      efficiently killed both MG63 and primary osteoblasts-like cells, and the addition
      of human Fas chimeric protein (hFas-Fc) significantly diminished the
      cytotoxicity, indicating that interactions between mFasL of activated PBMC and
      Fas on human osteoblasts induce apoptosis of the latter. Although dexamethasone
      did not affect apoptosis of MG63 and primary osteoblast-like cells induced by
      anti-Fas IgM, treatment of activated PBMC with dexamethasone markedly inhibited
      both mFasL expression and cytotoxicity of these cells against human osteoblasts,
      suggesting that dexamethasone preferentially acts not on osteoblasts but PBMC.
      Cultured supernatants from activated PBMC induced apoptosis of human osteoblasts
      and the addition of hFas-Fc also inhibited the cytotoxicity of the supernatants.
      In addition, soluble form FasL (sFasL) was detected in the supernatants of
      activated PBMC. Furthermore, both the cytotoxicity and sFasL concentration of
      cultured supernatants of activated PBMC incubated with dexamethasone was
      significantly lower than that in the absence of dexamethasone. Our data suggest
      that glucocorticoid suppresses the apoptotic process of osteoblasts by inhibiting
      the expression of both mFasL and sFasL derived from activated PBMC, mediating a
      protective effect against periarticular bone loss and bone erosion in
      inflammatory arthritis such as RA.

PMID- 9528992
TI  - Fas-induced apoptosis in rat thecal/interstitial cells signals through
      sphingomyelin-ceramide pathway.
AB  - Of the ovarian follicles that develop during reproductive life, more than 99% do
      not ovulate and are eliminated from the ovary by follicular atresia. Atresia is
      achieved by the self destruction of thecal and granulosa cells that comprise the
      follicle, by the process of apoptosis. The objective of this study was to
      determine if activation of the Fas receptor could enact apoptosis of thecal
      cells, and to explore the signal transduction pathway involved. Primary cultures
      of thecal/interstitial cells isolated from immature rat ovaries were treated with
      anti-Fas monoclonal antibody (anti-Fas mAb) (2.5 microg/ml). Morphological
      changes indicative of apoptosis, such as, condensation of chromatin,
      nucleoplasmic segmentation and formation of apoptotic bodies, were observed by
      fluorescence microscopy following nucleic acid staining with Hoechst 33342 dye
      and propidium iodide. DNA analysis of cells after 10 h of treatment with anti-Fas
      mAb showed that DNA had been cleaved into fragments that were multiples of 180
      300 bp in length; biochemical evidence of apoptosis. The sphingomyelin (N
      acylsphingosine-1-phosphocholine, SM) pathway that is initiated by the hydrolysis
      of SM to ceramide (Cer) has been shown previously to be activated by the Fas
      ligand/receptor system in a number of different cell types. It was therefore
      possible that the intracellular transduction of Fas receptor activation of
      thecal/interstitial cells could also involve the SM-Cer pathway. Hence, we have
      measured the SM levels in control and treated thecal/interstitial cells. Extracts
      of untreated thecal/interstitial cells contained six major species of SM
      identified as d18:1/16:0 (sphingosine base/fatty acid), d18:1/18:0, d18:1/20:0,
      d18:1/22:0, d18:1/24:1, d18:1/24:0 by normal phase high performance liquid
      chromatography interfaced with electrospray mass spectrometry. Treatment with
      anti-Fas mAb (2.5 microg/ml) for 30 min caused significant hydrolysis of only two
      of the SM species, d18:1/16:0 and d18:1/24:1. The involvement of ceramide, the
      central lipid in this phospholipid second messenger system, was tested using the
      synthetic cell permeable Cer analog (N-acetyl-N-sphingosine, C2-Cer). C2-Cer (10
      microM). This analog induced both morphological and biochemical changes in
      thecal/interstitial cells, that were characteristic of apoptosis, and the same as
      those induced by anti-Fas mAb. C2-dihydroceramide (10 microM), an inactive analog
      of C2-Cer, failed to induce apoptosis of thecal/interstitial cells. In
      conclusion, the sphingomyelin-ceramide cycle that can lead to cell suicide by
      apoptosis is functional and activated through the Fas ligand/receptor signal
      transduction pathway, not only in the immune system, but also in
      thecal/interstitial cells of the ovarian follicle.

PMID- 9528993
TI  - Estrogen receptor-alpha is developmentally regulated during osteoblast
      differentiation and contributes to selective responsiveness of gene expression.
AB  - Estrogen responsiveness of bone is a fundamental regulatory mechanism operative
      in skeletal homeostasis. We examined the expression of estrogen receptor-alpha
      (ER) messenger RNA (mRNA) in cultured rat calvarial-derived osteoblasts during
      progressive development of the osteoblast phenotype. Levels of ER message were
      compared with the expression of traditional osteoblastic markers that have been
      mapped throughout the differentiation process of these cells. ER transcripts,
      measured using semiquantitative RT-PCR analysis, were expressed at low levels in
      early stage proliferating osteoblasts and increased at confluence upon initial
      expression of bone cell phenotypic genes. A 23-fold up-regulation of ER mRNA
      expression coincided with the initiation of alkaline phosphatase activity (day
      8). ER mRNA levels progressively increased 70-fold, reaching a maximum level on
      days 22-25 in fully differentiated osteoblasts when osteocalcin expression
      peaked, but declined precipitously by day 32 in osteocytic cells. Analysis of RNA
      isolated directly from rat calvaria confirmed these in vitro results and
      demonstrated that ER message levels become more abundant postnatally as bone
      becomes more mineralized. We also examined the responsiveness of osteoblasts to
      17beta-estradiol (17beta-E2) at two periods of maturation: the nodule-forming
      stage (day 14) and the late mineralization stage (day 30). Estradiol suppressed
      the levels of alkaline phosphatase, osteocalcin, osteonectin, and ER mRNAs on day
      14, but up-regulated these messages on day 30. In contrast, 17beta-E2 treatment
      regulated the steady state levels of transforming growth factor-beta1 and type I
      procollagen mRNAs only in the late mineralization stage, whereas histone H4
      message was unaffected by the steroid at either stage of differentiation. Thus,
      the observed developmental expression of ER mRNA correlates with progressive
      osteoblast differentiation and may be a contributing factor to differential
      regulation of bone cell gene expression by 17beta-E2.

PMID- 9528994
TI  - Expression of D-type cyclins in normal and neoplastic rat pituitary.
AB  - The D-type cyclins (D1, D2, and D3) are involved in progression through the G1
      phase of the cell cycle and are induced as part of the delayed early response to
      growth factor stimulation. To better understand the role of D-type cyclins in
      pituitary cell function and the regulatory role of growth factors in the cell
      cycle, we analyzed the expression and regulation of D-type cyclins in normal and
      neoplastic rat pituitary cells. Immunocytochemical and RT-PCR analyses showed
      expression of all three D-type cyclins in the normal pituitary, with higher
      percentages of positive cells by immunocytochemistry in the nuclei of normal
      pituitaries (D1, 20-30%; D2, 50-60%; D3, 70-80%), compared with GH3 cells. In the
      normal pituitary, there were significantly higher levels of cyclins D2 and D3 in
      PRL, GH, LH, and TSH cells, compared with ACTH cells. Cyclin D1 protein was not
      detected in GH3 cells, while D2 was present in less than 1 percent and D3 in 10
      15 percent of GH3 cells. There were low levels of cyclin D1 and D2 messenger RNA
      expression in GH3 cells, by RT-PCR. When dissociated rat pituitary cells were
      cultured in the presence of basic fibroblast growth factor (5.6 nM) for 3 days,
      cyclin D2 was up-regulated 2-fold in normal PRL cells (control, 33 +/- 1%;
      treated, 68 +/- 2%). Similarly, bFGF treatment stimulated cyclin D3 expression 3
      fold in GH3 cells (control, 15 +/- 1%; treated, 44 +/- 1%). Treatment of GH3
      cells with 5-aza-2'-deoxycytidine, which induces gene demethylation, produced
      marked increases in cyclin D2 and D3 expression. Transfection of mouse cyclin D1
      complementary DNA, driven by a cytomegalovirus promoter into GH3 cells, led to
      ectopic cyclin D1 expression; and there was a slight stimulation of cell
      proliferation and increased apoptosis in GH3 cells. These results indicate that
      there is a differential expression of various D-type cyclins in different types
      of normal pituitary cells and between normal pituitary and GH3 cells. Growth
      factors, such as bFGF and demethylation increased D-type cyclin expression,
      whereas ectopic overexpression of cyclin D1 stimulates cell proliferation and
      increases apoptosis in GH3 pituitary tumor cells.

PMID- 9528995
TI  - Effects of CP-336,156, a new, nonsteroidal estrogen agonist/antagonist, on bone,
      serum cholesterol, uterus and body composition in rat models.
AB  - We have discovered a new, nonsteroidal, potent estrogen agonist/antagonist, CP
      336,156. CP-336,156 binds selectively and with high affinity to the human
      estrogen receptor-alpha with a half-inhibition concentration of 1.5 nM, which is
      similar to that seen with estradiol (4.8 nM). When given orally to immature (3
      week-old) female Sprague-Dawley rats for 3 days at doses of 0.1, 1.0, 10, or 100
      microg/kg x day, unlike 17alpha-ethynyl estradiol, CP-336,156 had no effect on
      uterine wet or dry weight. Similarly, no uterine hypertrophy was observed in aged
      (17-month-old) female rats treated (p.o.) with CP-336,156 at 10 or 100 microg/kg
      x day for 28 days. We also found that CP-336,156 decreased total serum
      cholesterol and fat body mass and had no effect on lean body mass in these aged
      female rats. In 5-month-old ovariectomized (OVX) Sprague-Dawley female rats, CP
      336,156 completely prevented OVX-induced increases in body weight gain, total
      serum cholesterol, and serum osteocalcin at doses between 10 and 1000 microg/kg x
      day after 4 weeks. At these doses, CP-336,156 completely prevented OVX-induced
      bone loss and inhibited the increased bone turnover associated with estrogen
      deficiency in lumbar vertebrae, proximal tibiae, and distal femora. Similar to
      estrogen, CP-336,156 induced apoptosis and p53 expression with a concomitant
      decrease in the number of tartrate-resistant acid phosphatase-positive
      multinuclear cells in rat bone marrow cell cultures in vitro, suggesting that the
      induction of apoptosis may be a mechanism for the estrogenic activities of CP
      336,156 in bone. In summary, CP-336,156 is a new, orally active, nonsteroidal,
      potent estrogen agonist/antagonist that has similar effects in bone as estradiol
      but without the uterine-stimulating effects associated with estradiol in rats.

PMID- 9528996
TI  - Expression of the MAL gene in the thyroid: the MAL proteolipid, a component of
      glycolipid-enriched membranes, is apically distributed in thyroid follicles.
AB  - The MAL proteolipid, an integral membrane protein expressed in T lymphocytes,
      polarized epithelial MDCK cells, and myelin-forming cells, has been identified as
      a component of internal glycolipid-enriched membrane (GEM) microdomains. On the
      basis of its ability to induce vesicle formation by ectopic expression, MAL has
      been recently proposed as a component of the machinery for GEM vesiculation.
      Taking into account the proposed role of GEMs in polarized transport, we have
      investigated the expression of the MAL gene in thyroid cells. Interestingly, MAL
      messenger RNA species were detected in the human thyroid, whereas they were
      undetectable in other endocrine glands tested. Moreover, epithelial FRT cells, a
      polarized rat cell line of thyroid origin, also expressed MAL transcripts.
      Immunohistochemical analysis of thyroid follicles, with a newly developed anti
      MAL monoclonal antibody, indicates that MAL distribution is restricted to the
      apical zone of thyroid epithelial cells. Biochemical analyses, using FRT cells,
      indicate exclusive residence of MAL in GEM microdomains, and these analyses
      allowed the identification of MAL as a major protein component of the GEM
      fraction in this cell line. Our results are consistent with a role for MAL as a
      component of GEM microdomains in thyroid epithelial cells.

PMID- 9528997
TI  - Glucagon-like-peptide-1 secretion from canine L-cells is increased by glucose
      dependent-insulinotropic peptide but unaffected by glucose.
AB  - Glucagon-like peptide-1(7-36)amide (GLP-1) is a potent insulinotropic peptide
      released from the small intestine. To investigate the regulation of GLP-1
      secretion, we established a GLP-1 release assay based on primary canine
      intestinal L-cells. The ileal mucosa was digested with collagenase/EDTA to a
      single cell suspension and enriched for L-cells by counterstream centrifugal
      elutriation. We performed release assays on the cultured cells after 36 h, and
      GLP-1 in the supernatant was determined by enzyme-linked immunoabsorbent assay
      (ELISA). Glucose-dependent insulinotropic peptide (GIP) dose dependently
      stimulated the release of GLP-1 and resulted in a 2-fold increase at 100 nM GIP.
      This effect was fully inhibited by 10 nM somatostatin. However, neither basal or
      GIP stimulated GLP-1 secretion were affected by ambient glucose concentrations
      from 5-25 mM. The receptor-independent secretagogues beta phorbol myristate
      acetate and forskolin dose dependently increased the secretion of GLP-1; effects
      inhibited by staurosporine and H8 respectively. Costimulation with GIP and
      phorbol ester, but not forskolin, resulted in an additive response. Furthermore,
      the effect of GIP could be inhibited by H8 but not by staurosporine. These
      results indicate that glucose does not directly stimulate canine L-cells. It is
      more probable that glucose releases GIP from the upper intestine that in turn
      stimulates GLP-1 secretion. The ability of GIP to stimulate GLP-1 secretion is
      probably mediated through activation of protein kinase A.

PMID- 9528998
TI  - Murine bone marrow stromally derived BMS2 adipocytes support differentiation and
      function of osteoclast-like cells in vitro.
AB  - Stromal cells are required for in vitro osteoclast differentiation and
      maturation. The murine bone marrow stromally derived BMS2 cell line exhibits
      adipocytic and osteoblastic features as well as the ability to support
      lymphopoiesis and myelopoiesis. This work examined the ability of the BMS2 cell
      in either the preadipocyte or adipocyte state to support the formation of
      osteoclast-like cells. BMS2 cells can be induced to undergo adipogenic
      differentiation in response to treatment with glucocorticoids or
      thiazolidinedione compounds. Primary bone marrow cells, enriched for
      hematopoietic progenitors and depleted of their adherent stromal and macrophage
      populations, were stimulated with vitamin D3 (vitamin D; 10(-8) M) to undergo
      osteoclast differentiation and maturation when cocultured with BMS2 cells. In
      both preadipocyte and adipocyte-enriched BMS2 stromal layers, comparable numbers
      of tartrate-resistant acid phosphatase-positive osteoclast-like cells,
      characterized by their response to salmon calcitonin with an increase in cAMP and
      formation of resorption pits on bovine bone slices, were formed. The gene
      expression and protein levels of macrophage colony-stimulating factor produced by
      preadipocyte and adipocyte-rich BMS2 layers were comparable. However, adipocyte
      rich stromal layers supported osteoclast-like cell formation longer in culture
      than preadipocytes, independent of the agent used to induce adipocyte
      differentiation. These studies demonstrate for the first time that fully
      differentiated adipocyte stromal cells can support osteoclast-like cell formation
      and function in vitro.

PMID- 9528999
TI  - Apoptotic regression of MCF-7 xenografts in nude mice treated with the vitamin D3
      analog, EB1089.
AB  - 1,25-Dihydroxyvitamin D3 [1,25-(OH)2D3] and its synthetic analog EB1089 induce
      characteristic morphological features of apoptosis in MCF-7 cells in vitro that
      coincide with up-regulation of clusterin and cathepsin B, proteins associated
      with apoptosis in the mammary gland, and with down-regulation of Bcl-2, an
      antiapoptotic protein. To determine whether vitamin D3 compounds could mediate
      apoptosis of breast tumors in vivo, we treated nude mice carrying established MCF
      7 xenografts with the low calcemic vitamin D3 analog EB1089 via daily injection
      or sustained release pellets for up to 5 weeks. The volume of tumors from mice
      treated with 45 pmol/day EB1089 was 4-fold lower than that of tumors from vehicle
      treated control mice after 5 weeks. The reduced growth of tumors from EB1089
      treated mice was associated with characteristic apoptotic morphology and a marked
      reduction in the proportion of epithelial cells to stroma. After 5 weeks of
      treatment with EB1089, MCF-7 tumors exhibited a 6-fold increase in DNA
      fragmentation (as measured by in situ end labeling) relative to that in control
      tumors. The enhanced rate of apoptosis in tumors from EB1089-treated mice was
      coupled to a 2-fold reduction in proliferation (as measured by expression of
      proliferating cell nuclear antigen) compared with that in tumors from control
      mice. The antitumor effects of EB1089 were evident at doses that had minimal
      effects on serum calcium and body weight. EB1089 treatment did not alter the
      growth of xenografts derived from a vitamin D3-resistant variant of MCF-7 cells
      (MCF-7(D3Res) cells), which display resistance to EB1089 in vitro, indicating
      that resistance to EB1089 is maintained in vivo. Tumors derived from both MCF-7
      and MCF-7(D3Res) cells underwent apoptotic regression upon estradiol withdrawal,
      indicating comparable estrogen dependence of tumors with differential sensitivity
      to vitamin D3 compounds. These are the first studies to demonstrate apoptotic
      morphology and regression of human breast tumors in response to treatment with a
      vitamin D3 analog in vivo and support the concept that vitamin D3 compounds can
      effectively target human breast cancer.

PMID- 9529000
TI  - Clathrin gene expression is androgen regulated in the prostate.
AB  - Androgens are required for the development and function of the prostate. In a
      normal human prostate, androgens control the synthesis of proteins such as
      prostate-specific antigen and human glandular kallikrein. The prostate secretes
      these proteins as well as a number of other compounds to form the prostatic
      fluid. Using differential display PCR to detect novel androgen-regulated genes,
      clathrin heavy chain expression was identified as potentially being up-regulated
      by androgens in the prostate cancer cell line LNCaP. We report here that the
      clathrin heavy chain and light chain genes are regulated by androgens. Clathrin
      heavy chain messenger RNA was up-regulated by androgens in a concentration- and
      time-specific manner in the LNCaP cell line. Translation of clathrin heavy chain
      messenger RNA was stimulated by androgens. Steady state levels of clathrin light
      chains a and b were up-regulated in the presence of androgen in LNCaP cells.
      Clathrin gene expression was examined in normal rat prostates, and similar
      results were found. Clathrin heavy chain protein levels in the rat prostate are
      also affected by the androgen status of the animal. We hypothesize that clathrin
      may be involved in the exocytosis of androgen-regulated secretory proteins such
      as prostate-specific antigen and human glandular kallikrein.

PMID- 9529001
TI  - Effects of parathyroid hormone (PTH) and PTH-related peptide on expressions of
      matrix metalloproteinase-2, -3, and -9 in growth plate chondrocyte cultures.
AB  - The roles of PTH and PTH-related peptide (PTH-rp) in the expression of matrix
      metalloproteinases (MMPs) during endochondral bone formation were investigated,
      using various cartilages obtained from young rabbits and rabbit chondrocyte
      cultures. Immunohistochemical, immunoblotting, zymographical, and/or Northern
      blot analyses showed that MMP-2 and -9 levels were much higher in the growth
      plate than in permanent cartilage in vivo. In growth plate chondrocyte cultures,
      PTH, PTH-rp, and (Bu)2cAMP increased the amount of MMP-2 present in the culture
      medium, as revealed by zymograms and immunoblots, whereas the other tested growth
      factors or cytokines, including bone morphogenetic protein-2 and interleukin-1,
      did not increase the MMP-2 level. PTH also increased the MMP-2 messenger RNA
      level within 24 h. In addition, PTH increased MMP-3 and -9 levels in the growth
      plate chondrocyte cultures. However, in articular chondrocyte cultures, PTH had
      little effect on the levels of MMP-2, -3, and -9. In contrast to PTH, interleukin
      1 induced MMP-3 and -9, but not MMP-2, in growth plate and articular
      chondrocytes. These findings suggest that in ossifying cartilage, PTH/PTH-rp
      plays a pivotal role in the induction of various MMPs, including MMP-2 (which is
      considered to be a constitutive enzyme), and that PTH/PTH-rp is involved in the
      control of cartilage-matrix degradation during endochondral bone formation.

PMID- 9529002
TI  - Orchidectomy induces a wave of apoptotic cell death in the epididymis.
AB  - The epididymis is the site where spermatozoa are matured and stored. After
      orchidectomy, this tissue loses up to 80% of its weight. In the prostate,
      androgen withdrawal by orchidectomy is associated with apoptotic cell death. The
      objective of the present study was to investigate whether apoptotic cell death is
      involved in the androgen-dependent weight loss found in the rat epididymis after
      orchidectomy. Adult male Sprague-Dawley rats were orchidectomized, and apoptotic
      cells were identified by in situ TUNEL (TdT-mediated dUTP-digoxigenin nick end
      labeling) apoptosis detection. Apoptosis first appeared in the epithelium of the
      initial segment of the epididymis 18 h after orchidectomy, reached a maximum on
      day 2, and disappeared by day 5 postorchidectomy. In the caput epididymidis,
      apoptosis was first found after 24 h, reached a maximum by day 3, and was
      detectable until day 5. In the corpus epididymidis, apoptosis was first seen on
      day 4, peaked on day 5, and was undetectable by day 6 postorchidectomy. In the
      cauda epididymidis, apoptosis was first seen on day 5, peaked on day 6, and was
      occasionally detected on day 7. Throughout the rat epididymis, apoptotic cell
      death was localized specifically to principal cells. The presence of apoptosis
      was confirmed with the observation of a ladder of nucleosomal sized DNA
      fragmentation by using agarose gel electrophoresis. Androgen replacement therapy
      after orchidectomy demonstrated that apoptosis in the caput, corpus, and cauda
      epididymidis was androgen dependent. However, androgens alone could not
      completely prevent apoptosis in the initial segment of the epididymis. Efferent
      duct ligation induced a similar pattern of apoptosis in the initial segment of
      the epididymis as that seen after orchidectomy, but there were fewer apoptotic
      cells in the caput epididymidis, and no apoptotic cell death in the corpus and
      cauda epididymidis. We conclude that withdrawal of androgen by orchidectomy
      induces a wave of apoptotic cell death in the epididymis; we hypothesize that
      apoptosis in the initial segment is caused primarily by withdrawal of androgen as
      well as by luminal components coming from the testis.

PMID- 9529003
TI  - Depletion of carboxypeptidase E, a regulated secretory pathway sorting receptor,
      causes misrouting and constitutive secretion of proinsulin and proenkephalin, but
      not chromogranin A.
AB  - Previous studies have shown that the prohormone POMC is sorted to the regulated
      secretory pathway (RSP), at the trans-Golgi network, by binding of a conformation
      dependent sorting signal to a sorting receptor, identified as membrane-bound
      carboxypeptidase E (CPE) (Cool et al., 1997, Cell, 88:73-83). In this study, the
      role of CPE as a sorting receptor for other RSP proteins that contain sorting
      signals (proinsulin, proenkephalin, and chromogranin A) was investigated in
      neuroendocrine cells (Neuro-2a) stably expressing CPE antisense RNA. Whereas
      these cells were depleted of CPE by greater than 85%, electron microscopy showed
      that they contain dense core secretory granules identical to wild-type Neuro-2a
      cells, indicating that CPE is not essential for granulogenesis. Secretion and
      immunocytochemical studies showed that, in wild-type Neuro-2a cells, endogenous
      proenkephalin and transfected proinsulin/insulin were localized to punctate
      secretory granules and were released via the RSP. However, in CPE-depleted cells,
      these two prohormones were released constitutively and had a Golgi-like
      distribution but were not localized to punctate secretory granules. In contrast,
      chromogranin A was present in punctate secretory granules and released via the
      RSP, in wild-type and CPE-depleted Neuro-2a cells. Thus, the sorting of
      proinsulin and proenkephalin to the RSP, like POMC, necessitates binding to CPE,
      and hence, CPE acts as a common sorting receptor for targeting these prohormones
      to the RSP. In contrast, the sorting signal of chromogranin A does not use CPE as
      a sorting receptor, suggesting the existence of other sorting receptors for the
      RSP.

PMID- 9529004
TI  - Insulin-like growth factor binding protein -2 and -4 messenger ribonucleic acid
      expression in bovine ovarian follicles: effect of gonadotropins and developmental
      status.
AB  - This work is concerned with the role of insulin-like growth factor binding
      protein (IGFBP)-2 and -4 in the regulation of IGF bioactivity in bovine follicles
      during the development of dominance. We measured the expression of IGFBP-2 and -4
      messenger RNA (mRNA) in small (1-4 mm) gonadotropin-sensitive follicles and
      medium (4-8 mm) and large (>8 mm) gonadotropin-dependent follicles using in situ
      hybridization. In healthy nonatretic bovine follicles, IGFBP-2 and -4 mRNA
      expression was confined to granulosa and theca tissue, respectively. Moreover,
      during the development of follicular atresia, there were distinct changes in the
      temporal and spatial expression of these genes. IGFBP-2 immunoactivity was
      localized in granulosa tissue and the basement membrane of healthy preantral
      follicles, whereas IGFBP-4 immunoactivity was localized in both theca and
      granulosa tissue. Of particular interest was the lack of IGFBP-2 mRNA expression
      in large (>8 mm) gonadotropin-dependent follicles, an observation that was
      confirmed by the lack of immunoreactive IGFBP-2 in these follicles. The
      regulation of IGFBP-2 and -4 mRNA expression in granulosa and theca cells was
      analyzed using a serum-free cell culture system. FSH inhibited the expression of
      IGFBP-2 mRNA in granulosa cells, whereas LH stimulated IGFBP-4 mRNA expression in
      theca cells. Our results provide evidence for the existence of different roles
      for IGFBP-2 and -4 in the developing follicle.

PMID- 9529005
TI  - Thymosin fraction 5 inhibits the proliferation of the rat neuroendocrine MMQ
      pituitary adenoma and C6 glioma cell lines in vitro.
AB  - Cytokines such as interleukin-1 (IL-1) and IL-6 stimulate the hypothalamic
      pituitary-adrenal (HPA) axis. In addition, these proteins affect pituitary cell
      proliferation in vitro. Thymosin fraction 5 (TF5) is a partially purified
      preparation of the bovine thymus that enhances immune system functioning. Because
      TF5 similarly stimulates the HPA axis, we examined the effects of this
      preparation on neuroendocrine tumor cell proliferation. Cells of the PRL
      secreting rat anterior pituitary adenoma, MMQ (5-50 x 10(3) cells/well), were
      exposed to vehicle (RPMI-1640 containing 2.5% FCS, 7.5% horse serum, and
      antibiotics) or TF5 (100-500 microg/ml) for up to 96 h and the proliferation of
      MMQ cells monitored using the MTT assay (3-(4, 5-dimethylthiazol-2-yl)-2,5
      diphenyl tetrazolium bromide). TF5-mediated inhibition of cell proliferation was
      dependent on both TF5 concentration and the initial MMQ cell number. Minimal
      reductions in optical densities resulted from exposure to 100 microg/ml TF5,
      whereas the highest concentration of this preparation (i.e. 500 microg/ml)
      completely blocked MMQ cell division. The concentration-dependent effects of TF5
      were particularly striking at initial plating densities of 25 and 50 x 10(3) MMQ
      cells/well; in contrast, all concentrations of TF5 completely inhibited MMQ cell
      growth at 5 and 10 x 10(3) cells/well. The antiproliferative actions of TF5 on
      MMQ cells were demonstrable within 24 h and remained for up to 96 h as determined
      by the MTT assay and actual cell counts. Because the highest densities of MMQ
      cells were partially refractive to the antiproliferative effects of TF5, we
      examined the effects of PRL (1-1000 nM) and MMQ cell conditioned medium (50%) on
      TF5 inhibition of MMQ adenoma proliferation. The TF5 concentration-dependent
      inhibition of MMQ cell growth was largely reversed by the 50% conditioned medium,
      whereas PRL slightly potentiated the antiproliferative actions of TF5. The
      proliferation of the rat C6 glioma cell line (10-30 x 10(3) cells/well)
      demonstrated greater sensitivity to TF5: concentrations as low as 10 microg/ml
      TF5 inhibited C6 cell proliferation (P < 0.01), and near-maximal inhibition was
      noted at 200 microg/ml TF5. Significant reductions in MMQ and C6 cell viabilities
      accompanied decreases in cell number and morphological analysis indicated these
      cells were dying by apoptosis. The peptides thymosin alpha1 (T alpha1), thymosin
      beta4 (T beta4), MB35, and MB40 had no effect on either MMQ or C6 cell
      proliferation, indicating that these TF5 components are not the principle active
      peptides. Therefore, TF5 was further separated into 60 fractions by preparative
      reverse phase HPLC. HPLC fractions 17, 25, 26, and 27 significantly suppressed
      MMQ cell proliferation (P < 0.01) to the same extent as TF5; other HPLC fractions
      had no effect. These data demonstrate a new biological property of TF5: the
      inhibition of cell proliferation and the induction of apoptosis in neuroendocrine
      tumor cells. The proliferation effects were time and concentration dependent and
      could be partially reversed by an activity present in the MMQ cell conditioned
      medium. Thus, TF5 and cytokines have opposite effects on adenoma cells because IL
      2 and IL-6 stimulate GH3 cell proliferation. We propose that circulating thymic
      peptides may act to prevent pituitary adenoma and glioma tumor formation, an
      action opposed by autocrine growth factors secreted by these tumors.

PMID- 9529006
TI  - Evidence that gonadotropin-releasing hormone stimulates gene expression and
      levels of active nitric oxide synthase type I in pituitary gonadotrophs, a
      process altered by desensitization and, indirectly, by gonadal steroids.
AB  - To determine the site and mechanism of action of gonadal steroids on pituitary
      nitric oxide synthase type I (NOS I), present in both gonadotrophs and folliculo
      stellate cells, the effects of castration and steroids were examined in male
      rats, in the presence of a GnRH antagonist (Antarelix). Western analysis showed a
      rapid and substantial increase with time, after orchidectomy, of NOS I protein,
      the concentration doubling in 24 h and reaching a maximal 4- to 5-fold increase
      after 3-7 days, followed by a progressive decline after 2 weeks. Testosterone or
      estradiol replacement, or administration of GnRH antagonist, totally abolished
      the effects of castration, demonstrating a mediation of the steroid effects via
      GnRH. In noncastrated rats, steroids and the GnRH antagonist also caused a
      reduction in the levels of NOS I (by 50-60%), consistent with inhibition of
      endogenous GnRH stimulation. In marked contrast, administration of a potent GnRH
      agonist (Triptorelin) to intact rats increased the levels of NOS I. A time-course
      study with a long-lasting formulation showed that rise in NOS I developed rapidly
      after a lag of approximately 5 h, with a 2-fold increase detectable after 8 h and
      a maximal 4.5-fold after 48 h. The level declined afterwards in a manner
      consistent with homologous desensitization that may occur in the continuous
      presence of GnRH; however, the profile was different and delayed compared with
      those of gonadotropin release. As observed for NOS I protein, NOS I messenger RNA
      concentration was increased by castration or GnRH agonist and reduced by steroids
      or GnRH antagonist. Taken together, these data demonstrate that steroids
      indirectly regulate NOS I messenger RNA and protein levels, through the
      hypothalamic modulation of GnRH, which represents the primary regulator of NOS I.
      No effect of steroids on NOS I was seen in the posterior lobe. NADPH-diaphorase
      histochemistry coupled to immuno-identification of the cells revealed that the
      treatments affecting the concentration of NOS I concomitantly altered the
      activity but exclusively in gonadotrophs and not in folliculo-stellate cells
      (which do not respond to GnRH), reinforcing the idea that GnRH played a major
      regulatory role. Expression in gonadotrophs of a GnRH-dependent NOS I and the
      ensuing production of nitric oxide represents a potentially novel signaling
      pathway for the neuropeptide in the anterior pituitary, consistent with the
      previously reported GnRH-induced cGMP production, the role of which remains to be
      evaluated.

PMID- 9529007
TI  - Transient expression of the 5alpha-reductase type 2 isozyme in the rat brain in
      late fetal and early postnatal life.
AB  - The enzyme 5alpha-reductase plays a key role on several brain functions
      controlling the formation of anxiolytic/anesthetic steroids derived from
      progesterone and deoxycorticosterone, the conversion of testosterone to
      dihydrotestosterone, and the removal of excess of potentially neurotoxic
      steroids. Two 5alpha-reductase isoforms have been cloned: 5alpha-reductase type 1
      is widely distributed in the body, and 5alpha-reductase type 2 is confined to
      androgen-dependent structures. In this study, the gene expression of the two
      5alpha-reductase isozymes has been analyzed in fetal, postnatal, and adult rat
      brains by RT-PCR followed by Southern analysis. 5Alpha-reductase type 1 messenger
      RNA is always detectable in the rat brain [from gestational day 14 (GD14) to
      adulthood]. 5Alpha-reductase type 2 messenger RNA expression is undetectable on
      GD14, increases after GD18, peaks on postnatal day 2, then decreases gradually,
      becoming low in adulthood. This pattern of expression appears to be correlated
      with the rate of production of testosterone by the testis. The possible control
      by androgens of gene expression of the two isozymes has been studied in brain
      tissues of animals exposed in utero to the androgen antagonist flutamide; the sex
      of the animals was determined by genetic sex screening of the SRY gene located on
      the Y-chromosome. In the brain of male embryos, flutamide treatment inhibited the
      expression of 5alpha-reductase type 2; this effect was much less pronounced in
      females. Moreover, 5alpha-reductase type 2 gene expression in cultured
      hypothalamic neurons is highly induced by testosterone and by the phorbol ester
      12-O-tetradecanoyl-phorbol-13 acetate. The transient, androgen-regulated,
      expression of 5alpha-reductase type 2 overlaps the critical period of
      development, which may be important for sexual differentiation of the brain and
      for the formation of anxiolytic/anesthetic steroids involved in the stress
      responses associated with parturition.

PMID- 9529008
TI  - Identification of multiple CYP19 genes encoding different cytochrome P450
      aromatase isozymes in brain and ovary.
AB  - Evidence to date indicates that the gene encoding cytochrome P450 aromatase
      (P450arom) in humans is a single member of the CYPl9 family, but multiple CYPl9
      loci and isoforms have been identified in pigs. Here we report the cloning and
      characterization of a second member of the CYP19 family in goldfish. A search for
      P450arom variants was prompted by studies showing that a full-length P450arom
      complementary DNA (cDNA) isolated from a goldfish brain cDNA library hybridizes
      with a high abundance 3 kb transcript in brain RNA but fails to detect a message
      in ovarian RNA. A stepwise PCR cloning strategy led to isolation of a 1.9-kb
      cDNA, which encodes a protein of 518 amino acids and has a predicted mol wt of
      58.7K. The ovary-derived P450arom (-A) shares 68-72% sequence identity with
      ovarian aromatases of other fish species, but only 62% identity with the
      homologous brain-derived P450arom (-B). Amino acid differences are distributed
      throughout the two goldfish P450arom forms, but presumptive functional domains
      are highly conserved. Both P450aromA and -B are able to aromatize [3H]androgen to
      [3H]estrogen when expressed in nonsteroidogenic COS cells. Southern analysis and
      PCR-restriction analysis of genomic DNA using discriminating probes and primers
      indicates that a single locus encodes the brain-derived P450aromB (CYPl9B),
      whereas one or two different loci encode the ovarian form (CYPl9A). Northern blot
      analysis revealed two P450aromA messenger RNAs (1.9 >> 3.0 kb) in ovary.
      Simultaneous PCR amplification with A- and B-specific primer pairs confirms that
      P450aromA is the only form expressed in ovaries, but shows overlapping expression
      of the two genes in neural tissues. Whereas P450aromB messenger RNA predominates
      in brain (B/A, approximately 14:1), the ratios are reversed in retina (B/A,
      approximately 1:25). Further studies are required to resolve the evolutionary and
      functional implications of multiple CYPl9 genes and P450arom isozymes in
      goldfish, their differential expression in brain and ovary, and whether
      observations can be generalized to other vertebrates.

PMID- 9529009
TI  - Macrophage-colony stimulating factor (M-CSF) regulates the expression of
      fibronectin and its alpha5 integrin receptor in human trophoblasts.
AB  - Macrophage-colony stimulating factor (M-CSF, CSF-1) is secreted by human
      trophoblasts as well as endometrial cells, while its receptor c-fms is abundantly
      expressed by the extravillous trophoblasts anchoring the placenta to the uterus,
      suggesting a role for M-CSF at the maternal-fetal interface. We investigated the
      effect of M-CSF on the expression of fibronectin and its receptor, the alpha5
      integrin, in human trophoblasts. Exposure of trophoblasts to M-CSF produced a two
      to three-fold increase in fibronectin and alpha5 mRNA abundance at both 24 and 72
      hours of culture. A dose-dependent increase in cellular fibronectin secretion
      into the culture medium was detected at both time points. Immunocytochemistry
      showed co-localization of cellular fibronectin and alpha5 in the cells,
      suggesting that attachment of trophoblasts to fibronectin is mediated in part by
      the alpha5beta1 integrin. We conclude that M-CSF increases fibronectin expression
      and secretion by the human trophoblasts, and up-regulates its specific receptor,
      the alpha5 integrin. We hypothesize that M-CSF may partake in the
      autocrine/paracrine mechanisms regulating trophoblast invasion during
      implantation.

PMID- 9529011
TI  - Mucoepidermoid carcinoma of the major salivary glands: clinical and
      histopathologic analysis of 234 cases with evaluation of grading criteria.
AB  - BACKGROUND: The authors had previously conducted an investigation of minor
      salivary gland mucoepidermoid carcinoma, in which they demonstrated that certain
      clinical and histopathologic features were useful in predicting biologic outcome.
      The current study investigated the usefulness of these features in determining
      the prognoses of patients with mucoepidermoid carcinomas of the major salivary
      glands. METHODS: Clinical data and 15 histopathologic features were compared in 4
      patient groups based on outcome after initial treatment. The outcome groups were
      1) survival without disease, 2) survival with tumor recurrence only, 3) survival
      with metastasis, and 4) death related to tumor. A numeric score was assigned to
      each unfavorable histopathologic feature. Low grade tumors had scores of 0-4.
      Intermediate grade tumors scored 5 or 6. High grade tumors had scores higher than
      6. RESULTS: Most patients (75%) were tumor free after the initial treatment.
      Twenty-one patients (9%) had local recurrence only, 12 (5%) demonstrated
      metastasis and survived, and 25 patients (11%) died of their disease.
      CONCLUSIONS: Clinical features associated with metastasis or death were more
      advanced age, tumor size, and preoperative symptoms. Histopathologic features
      that correlated with poor outcome were cystic component less than 20%, 4 or more
      mitotic figures per 10 high-power fields, neural involvement, necrosis, and
      anaplasia. All five of these histopathologic features demonstrated statistical
      prognostic significance when parotid gland tumors from Groups 1 and 4 were
      compared (P < 0.001). The point-based grading system demonstrated a statistically
      significant correlation with outcome for parotid tumors but not for submandibular
      tumors. The authors' findings indicate that patients with tumors of equal
      histopathologic grade have a better prognosis when their tumors are in the
      parotid gland than when their tumors are in the submandibular gland. Six of eight
      submandibular tumors that metastasized or resulted in death were low grade
      lesions, and none were high grade.

PMID- 9529010
TI  - Lowenhaupt's embryology-based classification of thymic tumors and the concept of
      granulomatous thymoma.

PMID- 9529012
TI  - The prognostic significance of microvessel density and thymidine phosphorylase
      expression in squamous cell carcinoma of the esophagus.
AB  - BACKGROUND: Squamous cell carcinoma (SCC) of the esophagus is among the most
      malignant of neoplasms and is associated with a dismal prognosis. Although tumor
      microvessel density (MVD) is an important prognostic factor in several
      carcinomas, its role in SCC of the esophagus is still controversial. Also, the
      role of thymidine phosphorylase (dThdPase), a key angiogenic growth factor, is
      yet to be delineated in this disease. METHODS: Immunohistochemical staining using
      monoclonal antibodies was used to quantify microvessel and dThdPase expression in
      archival tissue specimens from 93 patients with SCC of the esophagus. RESULTS:
      High dThdPase expression and high MVD were associated with tumor progression
      (size and stage) and lymph node metastasis, but only MVD was a predictor of
      survival. dThdPase expression was significantly correlated with depth of tumor
      invasion (P = 0.015). In multivariate analysis, MVD was an independent predictor
      of survival in the lymph node negative cases. A significant correlation was noted
      between MVD and dThdPase expression, with a correlation coefficient of 0.083 (P =
      0.002). CONCLUSIONS: MVD is an independent factor in determining the prognoses of
      lymph node negative patients with SCC of the esophagus. dThdPase could be a key
      factor in the angiogenesis of this disease and may be responsible for its
      aggressive behavior.

PMID- 9529013
TI  - Recent advances in surgical treatment have improved the survival of patients with
      gastric carcinoma.
AB  - BACKGROUND: Mortality resulting from gastric carcinoma is decreasing. This is
      mainly due to vigorous endoscopic screening and the consequent higher incidence
      of early detection of the disease. In this study, to evaluate the effect of
      surgical treatment on the prognoses of patients with gastric carcinoma, the
      survival of 1579 patients who underwent gastrectomy between 1970 and 1994 was
      retrospectively analyzed. METHODS: The patients were divided into 5 groups at 5
      year intervals. Postoperative survival was compared among the groups. RESULTS:
      Postoperative survival was significantly improved in the later groups for
      patients with Stage I, II, III, and IV disease. A multivariate analysis of
      prognostic factors revealed that the time period during which the gastrectomy was
      performed was an independent predictor of survival. CONCLUSIONS: It was concluded
      that survival has been improved by recent advances in the surgical approach to
      gastric carcinoma.

PMID- 9529014
TI  - Prognostic value of cyclin E and p53 expression in gastric carcinoma.
AB  - BACKGROUND: Cyclins and wild-type p53 are prime cell cycle regulators and may be
      involved in tumorigenesis. Cyclin E is a late G1 cyclin and its abnormalities
      have been reported in several cancers. The authors investigated the correlation
      between cyclin E expression and progression of gastric carcinoma. METHODS: The
      expression of cyclin E and p53 proteins was investigated retrospectively in 116
      patients with gastric carcinoma. Immunohistochemical staining of the paraffin
      sections was performed using monoclonal antibodies to cyclin E and p53. RESULTS:
      The total cyclin E positive rate was 44.0% (51 of 116) of all cases, 26 of which
      were strongly positive. Strong cyclin E expression frequently was observed in
      deeply invasive tumors, tumors with lymph node metastasis, and tumors of advanced
      stage. The incidence of p53 expression was higher in the cyclin E positive tumors
      than in the other tumors. With regard to prognosis, patients whose tumors had
      both strong positivity for cyclin E and positivity for p53 had significantly
      poorer prognosis. In multivariate analysis, the combined variable of cyclin E and
      p53 was an independent prognostic indicator together with serosal invasion and
      tumor size. CONCLUSIONS: These data suggest the cyclin E expression correlates
      with p53 expression and may contribute to the progression of gastric carcinoma.
      The combined variable of cyclin E and p53 expression could be a useful prognostic
      indicator in patients with gastric carcinoma.

PMID- 9529015
TI  - Intraoperative determinants of unresectability for patients with colorectal
      hepatic metastases.
AB  - BACKGROUND: Intrahepatic and extrahepatic factors are utilized by the surgeon in
      the decision-making process for the performance of hepatic resection for patients
      with colorectal metastases. Accurate preoperative and intraoperative staging are
      mandatory to avoid unnecessary surgery. In this report the intraoperative
      determinants of hepatic unresectability were evaluated. METHODS: This was a
      retrospective review of medical records from January 1985 to March 1996 of 62
      patients with colorectal hepatic metastases who at the time of exploratory
      laparotomy were deemed to have unresectable disease based on intrahepatic or
      extrahepatic factors. The stage of the primary tumor, disease free interval,
      preoperative carcinoembryonic antigen, computed tomography portography,
      intraoperative ultrasound, and assessment of intrahepatic and extrahepatic tumor
      extension were evaluated. RESULTS: Intraoperative determination of the extent of
      required hepatic resection, including trisegmentectomy (9 patients; 15%) and
      total hepatectomy (10 patients; 16%), accounted for the majority of unresectable
      patients. Patients with > 4 metastases (8 patients; 13%) and satellitosis (6
      patients; 10%) accounted for 23% of unresectable patients. Four patients had
      extensive nonmalignant hepatic parenchymal disease precluding resection. Thorough
      abdominal exploration revealed extrahepatic disease in 13 of 62 patients (21%).
      Routine periportal/celiac lymph node biopsies revealed metastases in an
      additional 12 patients (19%), 7 of whom (11%) had only periportal/celiac lymph
      node metastases. CONCLUSIONS: A meticulous abdominal exploration prior to hepatic
      resection for patients with colorectal metastases is essential to identify those
      patients with extrahepatic disease. Periportal and celiac lymph nodes commonly
      are involved by tumor. Therefore, routine periportal/celiac lymph node biopsies
      should be performed in the absence of other extrahepatic disease.

PMID- 9529016
TI  - Phase II trial of chemoembolization for the treatment of metastatic colorectal
      carcinoma to the liver and review of the literature.
AB  - BACKGROUND: Hepatic artery chemoembolization represents an alternative treatment
      for patients whose neoplastic lesions are not amenable or have become refractory
      to other treatment modalities. This project was designed to test the feasibility
      of regional chemoembolization for patients with colorectal carcinoma metastasis
      to the liver who had experienced failure with one or more systemic treatments.
      METHODS: Thirty patients who met the study entry criteria underwent one to three
      hepatic artery chemoembolizations. The chemoembolization regimen consisted of an
      injection of a bovine collagen material with cisplatin (10 mg/mL), doxorubicin (3
      mg/mL), and mitomycin C (3 mg/mL). Repeat treatments were performed at 6- to 8
      week intervals. RESULTS: Radiologic responses, as measured by a decrease in
      lesion density of at least 75% of the lesion or a 25% decrease in the size of the
      lesion, occurred in 63% of the cases. A decrease of at least 25% of the baseline
      carcinoembryonic antigen level occurred in 95% of the cases. All responses were
      transient. Median survival for all 30 patients was 8.6 months after the
      initiation of chemoembolization and 29 months after the initial diagnosis of
      metastasis to the liver. Common toxicities included a "postembolization
      syndrome," which consisted of fever > 101 degrees F (83%), pain in the right
      upper quadrant (100%), nausea, and vomiting. Lethargy was a common occurrence (in
      60+% of cases) and lasted up to 6 weeks. Hematologic toxicities included
      leukocytosis, anemia, and thrombocytopenia. CONCLUSIONS: Chemoembolization is a
      feasible treatment modality for patients with colorectal carcinoma metastasis to
      the liver who have experienced failure with other systemic treatments. It results
      in high response rates with transient mild-to-moderate toxicity. Responses are
      measured in months, however, and all patients have eventual progression of
      disease. Patients who are able to undergo three or more chemoembolization
      procedures may receive the most clinical benefit.

PMID- 9529017
TI  - Circulating platelet-derived endothelial cell growth factor increases in
      hepatocellular carcinoma patients.
AB  - BACKGROUND: Platelet-derived endothelial cell growth factor (PD-ECGF) is an
      angiogenic factor that is expressed in various cancer tissues. Little is known
      regarding plasma PD-ECGF levels in patients with chronic liver disease such as
      chronic hepatitis (CH), cirrhosis, and hepatocellular carcinoma (HCC) with
      cirrhosis. The expression of PD-ECGF in HCC tissues also remains to be clarified.
      METHODS: Plasma PD-ECGF levels in patients with chronic liver disease were
      determined with an enzyme-linked immunoadsorbent assay system using the mouse
      monoclonal antibodies specific to PD-ECGF. These were cross-sectionally compared
      among groups of normal persons, CH, cirrhosis, and HCC patients. The HCC patients
      were classified into two groups based on TNM stage: early and advanced stage
      disease groups. PD-ECGF expressions in HCC tissues were immunohistologically
      examined. RESULTS: The plasma PD-ECGF levels from the normal individuals and
      those with CH, cirrhosis, and HCC specimens were 4.2+/-0.5, 4.3+/-0.6, 4.6+/-1.1,
      and 6.0 +/-2.5 U/mL, respectively. The plasma PD-ECGF concentration was highest
      in HCC (P < 0.05). No significant difference was found among the normal subjects,
      CH, and cirrhosis specimens. Plasma PD-ECGF concentrations were significantly
      higher in the advanced stage disease HCC group compared with the early stage
      disease group (6.75+/-2.62 U/mL vs. 4.19+/-0.34 U/mL) (P < 0.05).
      Immunohistochemical expression of PD-ECGF in HCC cells increased significantly
      compared with normal liver cells (P < 0.05). CONCLUSIONS: Circulating PD-ECGF
      plasma level might be a new tumor marker for progression in patients with HCC.
      Immunohistological findings correspond to elevation of the plasma PD-ECGF in HCC
      patients. It is possible that increased production of PD-ECGF in HCC cells causes
      abundant neovascularization.

PMID- 9529018
TI  - Cryosurgery as a treatment for advanced stage hepatocellular carcinoma: results,
      complications, and alcohol ablation.
AB  - BACKGROUND: The objective of this study was to investigate the use of cryosurgery
      and to determine whether there is a role for combined therapy with alcohol
      ablation in the treatment of patients with hepatocellular carcinoma. METHODS:
      Twelve patients with biopsy proven hepatocellular carcinoma underwent ultrasound
      guided cryosurgical ablation of their liver tumor. Postoperative alcohol ablation
      was performed on those patients who were found to have residual tumor or
      recurrence after the cryosurgical procedure. RESULTS: Of the 12 patients (9
      males, 3 females) the size of the primary tumor ranged from 3-13 cm with average
      size of 7 cm in greatest dimension. Most patients had advanced disease according
      to the TNM staging system: 9 patients had Stage IVA disease, 2 Stage III, and 1
      Stage II. Three patients had residual tumors after the cryosurgical procedure.
      The residual tumor was treated with alcohol ablation. The 1-year survival rate
      for the entire group was 50% (5 of 10) and the 2-year survival rate was 30% (3 of
      10). At last follow-up, 1 patient with an 8-cm tumor was disease free for 3 years
      and another patient with a 13-cm tumor was disease free for 2.5 years. Both of
      these patients had Stage IVA disease. CONCLUSIONS: The authors found cryosurgery
      to be promising in the treatment of this extremely aggressive form of cancer,
      with the ability to prolong patient survival. Follow-up treatment with alcohol
      ablation is an important adjunct in treating residual tumor and controlling
      recurrences.

PMID- 9529019
TI  - Undifferentiated carcinoma with osteoclast-like giant cells of the pancreas and
      periampullary region.
AB  - BACKGROUND: Undifferentiated carcinomas with osteoclast-like giant cells are rare
      pancreatic and periampulary neoplasms that morphologically mimic giant cell tumor
      of bone. Despite numerous publications based primarily on single case reports,
      the terminology, histogenesis, and biologic behavior of these tumors remain
      controversial. METHODS: The authors studied one periampullary and nine pancreatic
      neoplasms of this type. Immunohistochemistry was performed on nine of the cases
      and clinical follow-up data was obtained in eight. RESULTS: The neoplasms were
      large (average 9 cm), partially or completely multicystic, and hemorrhagic.
      Histologically, they were composed predominantly of ovoid or spindle-shaped bland
      mononuclear cells and evenly spaced osteoclast-like giant cells. However, three
      neoplasms had foci in which the nuclear pleomorphism of the mononuclear cells
      approached that observed in anaplastic spindle and giant cell carcinomas. Other
      histologic features included phagocytosis of the mononuclear cells by the
      osteoclast-like giant cells (in 7 of 10 cases), osteoid or bone formation (in 3
      of 10 cases), and chondroid differentiation (in 1 of 10 cases). Four neoplasms
      had foci of conventional adenocarcinoma and two arose in preexisting mucinous
      cystic neoplasms of the pancreas. The mononuclear cells were positive for
      epithelial markers in six of nine tumors tested (cytokeratins AE-1, AE-3, Cam
      5.2, and/or epithelial membrane antigen). They were negative for the histiocytic
      markers (CD-68, lysozyme) in all nine cases tested. In contrast, the osteoclast
      like giant cells were positive for CD-68 in all nine cases, positive for lysozyme
      in four cases, and negative for cytokeratins (AE-1, AE-3, and Cam 5.2) in all
      nine cases. p53 stained the mononuclear tumor cells in three cases and MIB-1
      stained the mononuclear tumor cells in four cases, but the osteoclast-like giant
      cells did not stain with either antibody in all nine cases tested. Most of the
      patients died of disease within 1 year of diagnosis; only 1 patient was alive and
      disease free 14 years after surgical excision. CONCLUSIONS: The association of
      these tumors with conventional adenocarcinoma or mucinous cystic neoplasms, the
      histologic features, and the immunohistochemical profile supports an epithelial
      phenotype for the mononuclear cells and a reactive histiocytic lineage for the
      nonneoplastic osteoclast-like giant cells. These neoplasms, which are better
      classified as undifferentiated carcinomas, follow an aggressive clinical course;
      most patients die of disease within 1 year.

PMID- 9529021
TI  - bcl-2 and apoptosis in lymph node positive breast carcinoma.
AB  - BACKGROUND: Because bcl-2 can block apoptosis in vitro, and because lower levels
      of apoptosis might lead to malignant cell accumulation and therefore to a more
      aggressive clinical course, the authors tested the hypothesis that high bcl-2 and
      low apoptosis would result in a worse prognosis for breast carcinoma patients.
      METHODS: Primary breast tumor specimens from 979 patients with positive axillary
      lymph nodes were evaluated for bcl-2 protein expression by immunohistochemistry
      (IHC). Apoptosis was evaluated by using IHC to detect 3' DNA fragments end
      labeled with biotinylated uridine. Results were analyzed with respect to patient
      characteristics, prognostic factors, and clinical outcome. Median follow-up was
      61 months. RESULTS: High bcl-2 expression was significantly associated with a
      number of favorable prognostic factors, including a lower number of positive
      lymph nodes, absence of p53 protein accumulation, estrogen receptor (ER) and
      progesterone receptor (PR) positivity, diploidy, and a lower proliferative rate.
      However, although bcl-2 is generally considered a negative regulator of
      apoptosis, in these tumors there was no significant association between bcl-2 and
      apoptosis. Patients with high bcl-2 expression had significantly improved disease
      free survival (DFS) (P < 0.0001) and overall survival (OS) (P < 0.0001). In a
      multivariate analysis, bcl-2 expression was independently associated with better
      DFS (P = 0.004). Regarding apoptosis, the presence of > or = 1% apoptotic cells
      was significantly associated with a greater number of positive lymph nodes, p53
      protein expression, ER and PR negativity, aneuploidy, and a higher proliferation
      rate, although there was no significant association with a worse clinical outcome
      when this dichotomized cutoff was used. CONCLUSIONS: For lymph node positive
      breast carcinoma patients, high bcl-2 expression is associated with a number of
      good prognostic factors and is independently associated with better clinical
      outcome. Apoptosis is associated with a number of poor prognostic factors but not
      with a significantly worse outcome.

PMID- 9529020
TI  - A Southwest Oncology Group and Cancer and Leukemia Group B phase II study of
      doxorubicin, dacarbazine, ifosfamide, and mesna in adults with advanced
      osteosarcoma, Ewing's sarcoma, and rhabdomyosarcoma.
AB  - BACKGROUND: Ewing's sarcomas, osteosarcomas, and rhabdomyosarcomas are
      significantly more responsive to chemotherapy than other sarcomas. Adjuvant
      chemotherapy is used routinely based on data from randomized trials. Although a
      percentage of children with locally advanced or metastatic tumors remain curable,
      few data exist regarding the tumor's natural history or response and survival in
      adults. METHODS: This Phase II study evaluated doxorubicin, dacarbazine,
      ifosfamide, and mesna (MAID) in adults with inoperable or metastatic Ewing's
      sarcoma, rhabdomyosarcoma, or osteosarcoma. RESULTS: Between 1987-1991, 81
      patients were entered; 69 patients were eligible. One patient died of neutropenic
      infection. Ten patients (14%) responded completely and 34 patients (49%) had a
      complete or partial response. Response rates were significantly higher for
      patients with Ewing's sarcoma and rhabdomyosarcoma than for those with
      osteosarcoma (77%, 64%, and 26%, respectively; P < 0.005). Although there were no
      significant differences in progression free survival by histology, survival for
      patients with Ewing's sarcoma was significantly longer than for patients with
      osteosarcoma (P = 0.004.) At the time of last follow-up, 7 patients (10%) were
      alive without progression: 3 with Ewing's sarcoma, 1 with osteosarcoma, and 3
      with rhabdomyosarcoma. CONCLUSIONS: MAID chemotherapy is an active regimen in
      adults with advanced or metastatic Ewing's sarcoma and rhabdomyosarcoma. Although
      there was no direct comparison with a doxorubicin and cisplatin-based regimen,
      the response rate and survival in patients with osteosarcoma suggest that
      doxorubicin and cisplatin-based chemotherapy would remain the accepted initial
      chemotherapy regimen. For patients with rhabdomyosarcoma and Ewing's sarcoma, 10
      20% of patients remained disease free at 5 years.

PMID- 9529022
TI  - Treatment outcome with radiation therapy after breast augmentation or
      reconstruction in patients with primary breast carcinoma.
AB  - BACKGROUND: Analyses were performed to determine local control and cosmetic
      outcome of breast carcinoma patients with prosthetically augmented or
      reconstructed breasts who had received radiation therapy (RT). METHODS: Twenty
      one newly diagnosed breast carcinoma patients with prosthetically augmented or
      reconstructed breasts were treated with external beam RT. All patients received
      whole breast RT (median dose, 50.4 gray [Gy]) and 19 were boosted to a median
      dose of 60.4 Gy. A median dose of 50.4 Gy was delivered to the regional lymph
      nodes in 12 patients. Tissue equivalent bolus material was used in six patients.
      Seventeen patients received adjuvant systemic therapy. Cosmetic results were
      evaluated at 3-6-month intervals. RESULTS: With a median follow-up of 32 months,
      good/excellent cosmetic results were observed in 71% of patients (100% in those
      with augmented breasts and 54% in those with reconstructed breasts). Four
      patients (19%) with fair/poor cosmetic outcomes required implant removal and/or
      revision. Multiple clinical and treatment-related factors were analyzed for their
      impact on cosmetic outcome. A worsened cosmetic result was observed with
      increasing stage (P = 0.076), breast reconstruction (vs. augmentation) (P =
      0.030), and bolus application (P = 0.016). All patients with fair/poor cosmetic
      outcomes had time intervals from implant insertion to RT ranging from 53-213
      days. Two patients developed an isolated local recurrence within the augmented
      breast. CONCLUSIONS: Patients with prosthetically augmented breasts can undergo
      RT and expect good/excellent cosmetic results. Patients with reconstructed
      breasts are at a significantly greater risk for cosmetic failure. This risk may
      be related to the higher percentage of patients with advanced disease, those who
      received bolus application, and those who received earlier delivery of RT (after
      the cosmetic procedure) in reconstructed breasts.

PMID- 9529023
TI  - Breast carcinoma survival analysis for African American and white women in an
      equal-access health care system.
AB  - BACKGROUND: This retrospective review of breast carcinoma cases in the Department
      of Defense (DoD) Central Tumor Registry evaluated differences in survival
      patterns between African American and white women treated in U.S. military health
      care facilities. The study examined the effects of age, stage of cancer, tumor
      size, grade, lymph node involvement, waiting time between diagnosis and first
      treatment, marital status, military dependent status, alcohol usage, tobacco
      usage, and family history of cancer. METHODS: Researchers reviewed the tumor
      registry records of 6577 women (5879 whites and 698 African Americans) diagnosed
      with breast carcinoma. The patients, ages 19-97 years, were diagnosed between
      1975 and 1994. A hazard ratio (relative risk of mortality) model compared African
      American and white patients, adjusting for various combinations of covariates;
      impact of independent variables on the risk of death; prognostic factors
      significantly associated with survival; disease free and overall survival times;
      effects of ethnicity, stage, and age on survival; and trends in stage at
      diagnosis. A P value (2-sided) of less than 0.05 was considered statistically
      significant. RESULTS: After adjustment for age, the risk of death was 1.45 (95%
      confidence interval [CI], 1.20-1.76) times greater for African American women
      than for white women. Adjustment for stage reduced the risk to 1.41 (95% CI, 1.16
      1.70); further adjustment for demographic variables and most clinical variables
      had no effect. Still, African American women treated in the military health care
      facilities had a better survival rate than African American women represented in
      the Surveillance, Epidemiology, and End Results (SEER) Program of the National
      Cancer Institute. In our study, the 5-year risk of death, from any cause, was
      1.37 for African American women with breast carcinoma; in other words, the
      mortality rate for African American women was 24.77% compared with 18.08% for
      white women. In the latest SEER data, the 5-year relative risk of death for
      African American women compared with white women is 1.86. The mortality rate in
      SEER is 34.2% for African American women and 18.4% for white women. The survival
      rate for white DoD beneficiaries is comparable to that for white women in SEER.
      CONCLUSIONS: These observations suggest that ready access to medical facilities
      and the full complement of treatment options that are standard for all DoD
      patients improve survival rates for African American women. However, a
      significant unexplained difference in survival still exists between African
      American and white military beneficiaries.

PMID- 9529024
TI  - Telomerase activity and expression of its RNA component in cervical lesions.
AB  - BACKGROUND: The authors investigated telomerase enzyme activity and expression of
      its RNA component (hTR) during the multistage pathogenesis of cervical
      carcinomas, and correlated activation with histopathologic findings and human
      papillomavirus (HPV) infection. METHODS: The authors analyzed 180 cervical
      specimens for enzyme activity, and analyzed hTR expression in an additional 55
      samples from archival carcinoma cases. Polymerase chain reaction-based assays
      were used to determine telomerase enzyme activity and HPV infection, whereas a
      radioactive in situ assay was used for hTR expression. RESULTS: Telomerase enzyme
      activity was present in some samples of histologically normal epithelium (18 of
      138; 13%) and low grade squamous intraepithelial lesions (LSIL) (7 of 21; 33%),
      and in most high grade squamous intraepithelial lesions (HSIL) (13 of 21; 62%).
      The relative levels of telomerase activity were low in all preinvasive specimens
      except for three samples of HSIL with high activity. Although 21% of the brush
      samples had evidence of HPV infection, there was no obvious correlation between
      telomerase activity and HPV status. hTR expression was low in normal
      squamous/glandular epithelium and LSIL lesions, in which it was limited to the
      basal cells. In squamous and glandular in situ and invasive carcinomas, increased
      and dysregulated hTR expression was observed, although heterogeneity was noted.
      Intense focal up-regulation of hTR expression occurred in a subset of in situ
      lesions. CONCLUSIONS: Increased frequency and dysregulation of telomerase
      activation is correlated with increasing severity of histopathologic changes, but
      not with HPV infection. Whether dysregulated activity is a prognostic marker for
      development of invasive carcinoma remains to be determined.

PMID- 9529025
TI  - Poorer survival of nulliparous women with endometrial carcinoma.
AB  - BACKGROUND: Several epidemiologic studies have shown an inverse relationship
      between parity and the incidence of endometrial carcinoma. A prognostic influence
      of reproductive factors has been reported for carcinomas of the breast and
      uterine cervix; but no such independent influence has been reported for
      endometrial carcinoma, to the authors' knowledge. Therefore, the authors
      investigated the prognostic importance of parity in an unselected group of
      patients. METHODS: Clinical and histopathologic data on all 316 patients treated
      for endometrial carcinoma during the period 1981-1990 in Hordaland County,
      Norway, were related to cause specific death in univariate (Kaplan-Meier) and
      multivariate (Cox proportional hazards regression model) analyses. The median
      follow-up for the survivors was 9 years (range, 4-16 years). No patients were
      lost due to insufficient follow-up information. RESULTS: Nulliparous women had a
      poorer 5-year survival rate compared with patients who had had 1 or more
      deliveries (57% vs. 81%, P = 0.0001), and they were significantly older and had
      more advanced disease at the time of primary surgery than the parous women. After
      adjustment for traditional risk factors, a hazard ratio of 2.81 (95% confidence
      interval, 1.55-5.06) was found for nulliparous versus parous women. International
      Federation of Gynecology and Obstetrics stage, curative treatment, and tumor
      differentiation grade were also identified as independent prognostic factors,
      whereas age and menopausal status had prognostic significance in the univariate
      analysis only. CONCLUSIONS: The decreased survival among nulliparous women
      reported herein may reflect biologic differences between parous and nulliparous
      endometrial carcinoma patients. It may also be due in part to a greater delay in
      diagnosing the women in the nulliparous group.

PMID- 9529026
TI  - Predicting the outcome of radiotherapy for prostate carcinoma: a model-building
      strategy.
AB  - BACKGROUND: Clinical research of prostate carcinoma could be enhanced by models
      that allow early and reliable prediction of outcome. In this study, the authors
      describe a model-building strategy and compare different models. METHODS: The
      sample population was comprised of 158 patients treated definitively with
      radiotherapy. Univariate and multivariate logistic regression analyses were
      conducted to identify prognostic factors and select the best predictive model.
      Variables included age, race, method of diagnosis (needle biopsy vs.
      transurethral resection of the prostate), stage, grade, pretreatment prostate
      specific antigen (PSA), in-treatment PSA (PSA(tx)), posttreatment PSA
      (PSA(post)), and nadir PSA. The following indices were used to compare
      discriminatory power: log-likelihood function, Akaike information criterion, the
      generalized coefficient of determination, and the area under the receiver
      operating characteristic curve. RESULTS: At last follow-up, 49 patients (31%) had
      recurrence of carcinoma. By univariate analysis, the failure rate was
      significantly higher in patients with advanced stage, higher grade, higher
      pretherapy PSA, and nadir PSA > 1 ng/mL (P < 0.0001). Pretherapy PSA was
      associated significantly with stage, age, and nadir PSA (P = 0.001, P = 0.001,
      and P = 0.001, respectively). All PSA measurements were significantly
      interrelated. Nadir PSA was the most predictive variable. Significant gains (P =
      0.01) in predictive power were derived from inclusion of PSA(tx), but not PSA
      (post). Age, race, stage, grade, and method of diagnosis contributed predictive
      power in addition to that derived from PSA levels (P = 0.01, log-likelihood
      test). The authors' model of choice predicts outcome with an overall correctness,
      sensitivity, specificity, and false-negative rate of 81.8%, 87.2%, 79.6%, and
      12.8%, respectively. CONCLUSIONS: Applying the strategy described, a model was
      selected that allowed accurate prediction of failure shortly after the completion
      of therapy.

PMID- 9529027
TI  - Mature teratoma identified after postchemotherapy surgery in patients with
      disseminated nonseminomatous testicular germ cell tumors: a plea for an
      aggressive surgical approach.
AB  - BACKGROUND: Mature teratoma is often found in resected retroperitoneal residual
      tumor masses (RRTM) after chemotherapy for disseminated nonseminomatous
      testicular germ cell tumors (NSTGCT). The aim of this report is to describe the
      clinical course of patients after resection of residual teratoma, with particular
      emphasis on relapse with either growing mature teratoma or secondary non-germ
      cell malignancy. METHODS: During the period 1979-1995, 113 patients underwent a
      laparotomy for resection of RRTM after chemotherapy for NSTGCT. Only patients
      with mature teratoma in the RRTM were included in the current study, and data on
      the patients who experienced relapse were studied in detail. RESULTS: Mature
      teratoma was found in 51 patients (45.1%) with RRTM resected after chemotherapy.
      Nine of these 51 patients (17.6%) relapsed; the relapses resulted from growing
      mature teratoma in 5 patients (9.8%), secondary non-germ cell malignancy in 3
      patients (5.9%), and recurrent germ cell malignancy in 1 patient (2.0%). The
      primary treatment for all relapsing patients was surgical excision. All five
      patients with growing mature teratoma are alive without evidence of disease, as
      is the patient with recurrent germ cell malignancy. One of the three patients
      with non-germ cell malignancy died of disease, and the remaining two are alive
      with disease. CONCLUSIONS: Long term follow-up after resection of
      postchemotherapy residual teratoma is indicated because a proportion of patients
      develop growing mature teratoma or a secondary non-germ cell malignancy. The
      treatment for these recurrences should be complete surgical excision.

PMID- 9529028
TI  - Granulocyte-macrophage--colony stimulating factor in metastatic renal cell
      carcinoma: a phase II trial.
AB  - BACKGROUND: Due to lack of success with standard chemotherapy and only modest
      success with immunotherapy, metastatic renal cell carcinoma (RCC) is associated
      with a poor prognosis. Granulocyte-macrophage-colony stimulating factor (GM-CSF)
      is a cytokine with potential antitumor activity, including stimulation of tumor
      necrosis factor (TNF) and interleukin-1 secretion. It is also a potent growth
      factor for and activator of antigen-presenting dendritic cells. GM-CSF toxicity
      may be mediated by TNF, and inhibition of TNF release by pentoxifylline (PTX) may
      ameliorate these toxic effects. The authors conducted a Phase II trial to
      determine the activity of GM-CSF in metastatic RCC and to study the effect of PTX
      on GM-CSF toxicity. METHODS: Twenty-four eligible patients with metastatic RCC
      received 10 microg/kg of GM-CSF per day, administered subcutaneously, on a 14
      days-on/14-days-off schedule. Twelve patients received concurrent PTX at a dose
      of 400 mg administered orally 4 times per day. RESULTS: One patient experienced
      prolonged stability of disease after having progressive disease on entry. Two
      other patients experienced substantial slowing of their progressive disease while
      on study. One of these patients had rapidly progressing metastases on other
      immunotherapy before receiving GM-CSF. Toxicity was not diminished in patients
      treated with PTX; it included hyperleukocytosis, nausea, vomiting, pain, fever,
      skin reactions, myalgia, and fatigue. CONCLUSIONS: GM-CSF at the dose and
      schedule described in this report has minor activity against metastatic RCC, and
      PTX does not ameliorate its side effects.

PMID- 9529029
TI  - Prognostic values of matrix metalloproteinase-2 and tissue inhibitor of
      metalloproteinase-2 expression in bladder cancer.
AB  - BACKGROUND: Matrix metalloproteinase-2 (MMP-2), which degrades the extracellular
      matrix or the basement membrane, has an essential role in tumor invasion and
      metastasis. To evaluate the roles of MMP-2, its inhibitor (tissue inhibitor of
      metalloproteinase-2 [TIMP-2]), and its activator (membrane-type matrix
      metalloproteinase-1 [MT1-MMP]) in tumor invasion or as a prognostic factor in
      patients with bladder carcinoma, the authors investigated the expression of MMP
      2, TIMP-2, and MT1-MMP in patients with bladder carcinoma. METHODS: Tissues
      obtained from 41 patients with bladder carcinoma were used for analysis.
      Expression of MMP-2, TIMP-2, MT1-MMP, and glyceraldehyde-3-phosphate
      dehydrogenase was examined by reverse transcriptase-polymerase chain reaction
      analysis. Correlations between the levels of MMP-2, TIMP-2, and MT1-MMP
      expression and histologic findings or patient outcome were evaluated. RESULTS:
      Expression of MMP-2 and TIMP-2 was significantly higher in muscle invasive pT2<
      or = bladder tumors than in pT1a tumors (MMP-2: P < 0.0005; TIMP-2: P < 0.005).
      Moreover, high levels of MMP-2 and TIMP-2, as well as MT1-MMP expression, all
      were strongly associated with decreased survival (MMP-2: P < 0.0001; TIMP-2: P <
      0.0001; and MT1-MMP: P < 0.005). Even within the radically cystectomized muscle
      invasive pT2< or = tumor group, patients with a high expression of any of these
      three genes had a worse prognosis than those with low expression (MMP-2: P <
      0.05; TIMP-2: P < 0.05; and MT1-MMP: P = 0.0641). CONCLUSIONS: MMP-2 and TIMP-2
      are believed to contribute to the invasive properties of bladder carcinoma. The
      authors report that expression of MMP-2, TIMP-2, and MT1-MMP are useful
      prognostic indicators in patients with bladder carcinoma and may be helpful in
      designing treatment protocols.

PMID- 9529030
TI  - Smoking tobacco, oral snuff, and alcohol in the etiology of squamous cell
      carcinoma of the head and neck: a population-based case-referent study in Sweden.
AB  - BACKGROUND: This case-referent study was conducted to elucidate the role of
      selected exogenous agents in the etiology of head and neck cancer. The factors
      studied were tobacco smoking, alcohol intake, the use of moist oral snuff,
      dietary factors, occupational exposures, and oral hygiene. In this first report,
      the authors discuss the impact of tobacco smoking, the use of oral snuff, and
      alcohol consumption. METHODS: The study base was approximately 2 million person
      years at risk and consisted of Swedish males age 40-79 years living in 2
      geographic regions during the years 1988-1990. A total of 605 cases were
      identified in the base, and 756 controls were selected by stratified random
      sampling from population registries covering the base. RESULTS: Among those who
      were tobacco smokers at the time of the study, the relative risk of head and neck
      cancer was 6.5% (95% confidence interval, 4.4-9.5%). After cessation of smoking,
      the risk gradually declined, and no excess risk was found after 20 years. The
      relative risk associated with alcohol consumption of 50 grams or more per day
      versus less than 10 grams per day was 5.5% (95% confidence interval, 3.1-9.6%).
      An almost multiplicative effect was found for tobacco smoking and alcohol
      consumption. CONCLUSIONS: Tobacco smoking and alcohol intake had a strong
      interactive effect on the risk of squamous cell carcinoma of the head and neck.
      Moderate alcohol intake (10-19 grams per day) had little or no effect among
      nonsmokers. No increased risk was found for the use of Swedish oral snuff.

PMID- 9529031
TI  - Molecular support for field cancerization in the head and neck.
AB  - BACKGROUND: Two competing concepts, field cancerization and micrometastatic
      lesions, have been postulated to account for the high frequency of second primary
      tumors and multicentric dysplasia in patients with head and neck carcinoma.
      METHODS: To provide insight into this process, the authors examined
      histologically normal mucosa and dysplastic tissue adjacent to invasive tumor for
      loss of heterozygosity (LOH) at three commonly deleted loci. Tissues from 21
      patients with carcinoma of the oral cavity and oropharynx were identified and
      verified by a pathologist to contain histologically normal mucosa, dysplasia, and
      adjacent invasive squamous cell carcinoma. Each specimen was analyzed for LOH at
      D9S171 (9p21), D3S1007 (3p21.3-22), and D3S1228 (3p14). RESULTS: Of the 21
      patients, 19 had adequate DNA for analysis. Seventeen patients were heterozygous
      at one or both of the 3p sites and LOH occurred in 6 of 17 invasive tumor
      specimens, 1 of 17 dysplasia specimens, and in none of the mucosal specimens. LOH
      at 9p21 occurred in 11 of 13 informative specimens of invasive tumor, 8 of 13
      dysplasia specimens, and 6 of 13 normal mucosa specimens. However, one case that
      did not have 9p deletion in the tumor demonstrated LOH in the mucosa and two
      cases had LOH in both the tumor and mucosa but with deletion of the opposite
      allele. CONCLUSIONS: These data suggest that 9p21 but not 3p14 or 3p21 deletions
      occur in the absence of histologic changes. In two cases preinvasive and invasive
      lesions that apparently were an example of histologic progression contained
      disparate genetic events, calling into question the use of adjacent dysplasia as
      a model for premalignant lesions.

PMID- 9529032
TI  - A phase II trial of paclitaxel in refractory germ cell tumors.
AB  - BACKGROUND: A significant percentage of patients with refractory germ cell tumors
      will not respond to standard salvage regimens. Thus there is a need for new
      active agents. Paclitaxel has demonstrated activity against a variety of solid
      tumors in both laboratory and clinical studies. METHODS: Eighteen patients with
      refractory germ cell tumors who failed initial cisplatin-based chemotherapy and a
      maximum of 2 salvage regimens were enrolled into a Phase II trial of paclitaxel
      at a dose of 170 mg/m2 by intravenous infusion over 24 hours every 21 days
      without growth factor support. The median age of the patients was 32.5 years
      (range, 18-49 years). The testis was the primary site of tumor for 13 patients
      (72%) and the tumor was extragonadal in 5 patients (28%). Six patients (33%) were
      late recurrences. Twelve patients (67%) had > or = 2 metastatic sites. The median
      number of previous chemotherapy cycles was six (range, four to nine). Three
      patients (17%) previously had undergone autologous bone marrow transplantation.
      RESULTS: Two patients (11%) responded to paclitaxel. Major toxicities were Grade
      3-4 neutropenia (55% of patients) and Grade 3-4 neurotoxicity (2 patients).
      Neutropenic fever occurred in 3 patients (17%). CONCLUSIONS: Paclitaxel
      demonstrated minimal activity in heavily pretreated patients with multiple, poor
      risk clinical features. These results in part may be due to the unfavorable
      characteristics of the patients in the current study, specifically the high
      percentage of patients with late recurrences and extragonadal primary tumors,
      both of which are known to respond poorly to salvage therapy. Other trials with
      different patient populations and doses of paclitaxel reported response rates
      ranging from 13.3%-26%. The role of paclitaxel in the treatment of patients with
      refractory germ cell tumors remains to be defined in future studies.

PMID- 9529033
TI  - Survival after relapse in childhood acute lymphoblastic leukemia: impact of site
      and time to first relapse--the Children's Cancer Group Experience.
AB  - BACKGROUND: Childhood acute lymphoblastic leukemia is the single most common
      childhood malignancy. Despite substantial improvements in therapy, cases in which
      relapse occurs are still more common than newly diagnosed cases of many other
      childhood cancers. The survival of patients who relapse despite improved therapy
      continues to be of interest. METHODS: One thousand one hundred forty-four
      relapses and 28 second malignant neoplasms were identified among the 3712
      eligible patients enrolled on Children's Cancer Group trials between 1983 and
      1989. The details of treatment after relapse were not accessible. Subsequent
      secondary event free survival and overall survival were examined by the site of
      and time to initial relapse. A variety of potential prognostic factors were
      examined employing the log rank statistic and Wilcoxon regression model. RESULTS:
      Rates of 6-year survival (+/- standard error) after isolated bone marrow,
      isolated central nervous system (CNS), and isolated testis relapse were 20%+/-2%,
      48%+/-4%, and 70%+/-5%, respectively. Rates of survival after isolated bone
      marrow relapse at 0-17 months, 18-35 months, and after 36 months were 6%+/-2%,
      11%+/-2%, and 43%+/-4%, respectively. Rates of survival after isolated CNS
      relapse at 0-17 months, 18-35 months, and after 36 months were 33%+/-4%, 59%+/
      5%, and 72%+/-8%, respectively. Rates of survival after isolated testis relapse
      at 0-17 months, 18-35 months, and after 36 months were 52%+/-11%, 57%+/-10%, and
      81%+/-5%, respectively. Rates of survival after combined bone marrow and CNS or
      testis relapse at 0-17 months, 18-35 months, and after 36 months were 9%+/-5%,
      11%+/-6%, and 49%+/-7%, respectively. CONCLUSIONS: Substantial survival at 6
      years is evident among several subsets of this unselected group of
      heterogeneously treated children, namely, those with isolated or combined bone
      marrow relapse after 36 months and those with isolated extramedullary relapse at
      any time. Second malignant neoplasms are rare thus far.

PMID- 9529034
TI  - Increased incidence of cancer in infants in the U.S.: 1980-1990.
AB  - BACKGROUND: During the decade between 1980-1990, the rate of cancer in children
      in the U.S. increased. It is unknown whether cancer in infancy, which is
      biologically and clinically different from cancer in older children, also
      increased. METHODS: To evaluate changes in cancer incidence in infants in the
      U.S. age < 1 year, data from the Surveillance, Epidemiology, and End Results
      (SEER) program and the U.S. Bureau of the Census were used to construct age
      specific, population-based cancer incidence rates. RESULTS: Overall, the annual
      cancer rate in infants increased from 189 cases per million infants between 1979
      1981 to 220 between 1989-1991. At both timepoints, female infants had higher
      cancer rates than male infants. Although the rates for female infants remained
      stable at 223 between 1979-1981 versus 236 between 1989-1991, rates for male
      infants increased from 158 to 205 during the same timepoints. Male infants had
      increased rates of central nervous system (CNS) tumors (P < 0.05), neuroblastoma,
      and retinoblastoma; female infants had increased rates of teratomas (P < 0.01)
      and hepatoblastomas. Between 1979-1981, the three most common types of cancer in
      infants were neuroblastoma, leukemia, and renal tumors (27%, 15%, and 14%,
      respectively), and were neuroblastoma, CNS tumors, and leukemia between 1989-1991
      (27%, 15%, and 13%, respectively). CONCLUSIONS: This study shows that the rate of
      certain types of cancer in infants in the U.S. is increasing. Studies of both
      genetic and environmental factors are needed to explain these increased rates and
      the changing distribution of cancer in the first year of life.

PMID- 9529035
TI  - The American Cancer Society research program: new directions, new opportunities.

PMID- 9529036
TI  - International Union Against Cancer, Committee on International Collaborative
      activities: Gulf States Symposium on Cancer Registration.

PMID- 9529037
TI  - The relation of age, race, and gender to the subsite location of colorectal
      carcinoma.

PMID- 9529038
TI  - Predictors of axillary lymph node metastases in patients with T1 breast
      carcinoma.

PMID- 9529039
TI  - Use of primary breast carcinoma characteristics to predict lymph node metastases-
      reply.

PMID- 9529040
TI  - Is primitive neuroectodermal tumor of the kidney a distinct entity?

PMID- 9529041
TI  - A neuroblastoma cell line derived from a case detected through a mass screening
      system in Japan: a case report including the biologic and phenotypic
      characteristics of the cell line.

PMID- 9529042
TI  - Macrophage receptors for Mycobacterium tuberculosis.

PMID- 9529043
TI  - Chlamydial infection in inducible nitric oxide synthase knockout mice.
AB  - Type 1 CD4+-T-cell-mediated immunity is crucial for the resolution of chlamydial
      infection of the murine female genital tract. Previous studies demonstrating a
      correlation between CD4+-T-cell-mediated inhibition of chlamydial growth and
      gamma interferon (IFN-gamma)-mediated induction of nitric oxide synthase
      suggested a potential role for the nitric oxide (NO) effector pathway in the
      clearance of Chlamydia from genital epithelial cells by the immune system. To
      clarify the role of this pathway, the growth levels of Chlamydia trachomatis
      organisms in normal (iNOS+/+) mice and in genetically engineered mice lacking the
      inducible nitric oxide synthase (iNOS) gene (iNOS-/- mice) were compared. There
      was no significant difference in the course of genital chlamydial infections in
      iNOS+/+ and iNOS-/- mice as determined by recovery of Chlamydia organisms shed
      from genital epithelial cells. Dissemination of Chlamydia to the spleen and lungs
      occurred to a greater extent in iNOS-/- than in iNOS+/+ mice, which correlated
      with a marginal increase in the susceptibility of macrophages from iNOS-/- mice
      to chlamydial infection in vitro. However, infections were rapidly cleared from
      all affected tissues, with no clinical signs of disease. The finding of minimal
      dissemination in iNOS-/- mice suggested that activation of the iNOS effector
      pathway was not the primary target of IFN-gamma during CD4+-T-cell-mediated
      control of chlamydial growth in macrophages because previous reports demonstrated
      extensive and often fatal dissemination of Chlamydia in mice lacking IFN-gamma.
      In summary, these results indicate that the iNOS effector pathway is not required
      for elimination of Chlamydia from epithelial cells lining the female genital
      tract of mice although it may contribute to the control of dissemination of C.
      trachomatis by infected macrophages.

PMID- 9529044
TI  - Influence of antibodies in mother's milk on antigenic variation of Giardia
      lamblia in the murine mother-offspring model of infection.
AB  - In the present study, neonatal ZU.ICR mice and their mothers were infected with
      trophozoites of Giardia lamblia clone GS/M-83-H7 expressing the variant surface
      protein (VSP) H7. The infection experiments included a detailed analysis of the
      specificities of anti-Giardia immunoglobulin A (IgA) antibodies in mother's milk
      and a determination of the effects of the milk antibodies on both the growth of
      the parasite during in vitro cultivation and colonization of the parasite within
      the intestine of suckling offspring. These investigations revealed that
      transiently emerging milk IgA antibodies against a variant-specific 314-amino
      acid N-terminal region of VSP H7 exhibit a strong parasiticidal effect on VSP H7
      type trophozoites both in vitro and in vivo. These findings indicated that
      parasiticidal effects of local IgA antibodies against the N-terminal part of VSP
      H7 select for new variant types within the intestinal parasite population of
      suckling mice. The selective influence of such antibodies promotes in vivo
      antigenic variation of G. lamblia clone GS/M-83-H7 and modulates the early course
      of parasite infection in these animals.

PMID- 9529045
TI  - Superoxide dismutase-dependent, catalase-sensitive peroxides in human endothelial
      cells infected by Rickettsia rickettsii.
AB  - The generation and intracellular accumulation of reactive oxygen species have
      been shown to be associated with the infection of human umbilical vein
      endothelial cells (HUVEC) by Rickettsia rickettsii. In response to the oxidant
      superoxide, the activity of the enzyme superoxide dismutase (SOD) increases
      following infection by this obligate intracellular bacterium. Other oxidants
      which are capable of oxidizing the fluorescent probe 2',7'-dichlorofluorescin
      (DCFH) also accumulate intracellularly within infected cells. In the study
      reported here, we show that (i) an inhibitor of SOD, diethyldithiocarbamic acid,
      reduces the observed rise in SOD activity in infected cells by 40 to 60% and at
      the same time reduces the degree of intracellular oxidation of DCFH; (ii)
      catalase-sensitive peroxides can be detected in supernatants of R. rickettsii
      infected cells shortly after rickettsial exposure; and (iii) fluorescence
      activated cell sorter analysis demonstrates significant intracellular oxidant
      activity in infected cells within 5 h after exposure to R. rickettsii. The
      results of these experiments indicate that hydrogen peroxide is a major oxidant
      associated with infection of HUVEC by R. rickettsii and that intracellular
      oxidant activity sensitive to SOD inhibition is detectable early and prior to
      significant rickettsial multiplication and much earlier than the ultrastructural
      manifestations of cell injury seen by electron microscopy.

PMID- 9529046
TI  - Glycosphingolipids as novel targets for T-cell suppression by the B subunit of
      recombinant heat-labile enterotoxin.
AB  - Heat-labile enterotoxin subunit B (LTB) is a noncatalytic protein derived from
      Escherichia coli that binds to ganglioside GM1, a glycosphingolipid on the
      surface of mammalian cells. In this study, the effects of recombinant LTB (rLTB)
      on murine lymphocytes were examined in vitro. T and B cells readily bound
      fluorescein isothiocyanate-labeled rLTB. CD8+ T cells bound twice as much as CD4+
      T cells and B cells. Exposure of T-cell subsets and B cells to rLTB abrogated
      mitogen-driven proliferation. CD8+ T cells were more susceptible to rLTB than
      either CD4+ T cells or B cells. There were differences in the sensitivity of
      lymphocytes from various strains of mice to rLTB. This was attributed to
      qualitative and quantitative differences in the CD4+ T cells. rLTB induced
      apoptosis in both T-cell subsets, but the level was significantly higher in CD8+
      T cells. Apoptosis peaked at around 8 h after exposure to rLTB and incubation at
      37 degrees C. Binding to ganglioside GM1 was essential for suppression, since
      rLTB/G33D, a mutant which does not bind GM1, failed to inhibit proliferation or
      induce apoptosis. Naive T cells, which were acutely sensitive to rLTB, became
      more resistant after activation. Conversely, activated T cells regained their
      sensitivity to rLTB when they reverted back to a resting state. A 1-h pulse with
      rLTB was sufficient to inhibit T-cell proliferation and cytotoxic-T-lymphocyte
      generation in primary mixed lymphocyte reaction cultures. CD8+ T cells were
      preferentially depleted in these cultures. rLTB also induced functional
      modifications in T cells as indicated by inhibition of gamma interferon secretion
      after polyclonal activation. Thus, rLTB may have immunomodulatory properties
      independent of its ability to induce apoptosis.

PMID- 9529048
TI  - Molecular cloning and characterization of the genes coding for the highly
      immunogenic cluster of 90-kilodalton envelope proteins from the Chlamydia
      psittaci subtype that causes abortion in sheep.
AB  - Proteins present in the outer membrane of chlamydiae that are involved in mucosal
      epithelial cell infection must clearly be identified and characterized if we are
      to understand and modify the pathogenic mechanisms utilized by these organisms.
      We have identified and isolated a family of four genes encoding putative outer
      membrane proteins (POMPs), a group of proteins of approximately 90 kDa present in
      the outer membrane of the subtype of Chlamydia psittaci that causes ovine
      enzootic abortion (strain S26/3). These proteins, although minor components, are
      major immunogens, as shown by the immunoblotting of chlamydial outer membrane
      complexes with postabortion sheep sera, and are therefore potential diagnostic
      and/or protective antigen candidates. Immunoblotting of the expressed amino- and
      carboxy-terminal halves of one of the POMPs with postabortion sheep sera showed
      that the major humoral immune response appeared to be directed solely against the
      amino-terminal half. This result, in combination with the positive
      immunofluorescence staining of S26/3-infected cells using POMP-specific (specific
      to the amino-terminal half of the proteins) monoclonal antibodies, suggests the
      probable surface localization of the POMPs and, more specifically, the surface
      exposure of the amino-terminal half of these proteins. The four pomp genes are
      highly homologous, sharing 82 to 100% similarity with each other (two of the
      genes are identical). Genes with strong and weak homologies were also detected in
      C. psittaci avian and feline pneumonitis strains, respectively. No pomp homologs
      were found in strains of C. trachomatis and C. pneumoniae, but this does not
      preclude their existence. The absence of homology with various subtypes of C.
      pecorum, which complicate the diagnosis of the ovine abortion subtype, indicates
      the possible suitability of the these 90-kDa proteins as serodiagnostic antigens.

PMID- 9529047
TI  - Expression and bactericidal activity of nitric oxide synthase in Brucella suis
      infected murine macrophages.
AB  - We examined the expression and activity of inducible nitric oxide synthase (iNOS)
      in both gamma interferon (IFN-gamma)-treated and untreated murine macrophages
      infected with the gram-negative bacterium Brucella suis. The bacteria were
      opsonized with a mouse serum containing specific antibrucella antibodies (ops
      Brucella) or with a control nonimmune serum (c-Brucella). The involvement of the
      produced NO in the killing of intracellular B. suis was evaluated. B. suis
      survived and replicated within J774A.1 cells. Opsonization with specific
      antibodies increased the number of phagocytized bacteria but lowered their
      intramacrophage development. IFN-gamma enhanced the antibrucella activity of
      phagocytes, with this effect being greater in ops-Brucella infection. Expression
      of iNOS, interleukin-6, and tumor necrosis factor alpha (TNF-alpha) mRNAs was
      induced in both c-Brucella- and ops-Brucella-infected cells and was strongly
      potentiated by IFN-gamma. In contrast to that of cytokine mRNAs, iNOS mRNA
      expression was independent of opsonization. Similar levels of iNOS mRNAs were
      expressed in IFN-gamma-treated cells infected with c-Brucella or ops-Brucella;
      however, expression of iNOS protein and production of NO were detected only in
      IFN-gamma-treated cells infected with ops-Brucella. These discrepancies between
      iNOS mRNA and protein levels were not due to differences in TNF-alpha production.
      The iNOS inhibitor N omega-nitro-L-arginine methyl ester increased B. suis
      multiplication specifically in IFN-gamma-treated cells infected with ops
      Brucella, demonstrating a microbicidal effect of the NO produced. This
      observation was in agreement with in vitro experiments showing that B. suis was
      sensitive to NO killing. Together our data indicate that in B. suis-infected
      murine macrophages, the posttranscriptional regulation of iNOS necessitates an
      additive signal triggered by macrophage Fcgamma receptors. They also support the
      possibility that in mice, NO favors the elimination of Brucella, providing that
      IFN-gamma and antibrucella antibodies are present, i.e., following expression of
      acquired immunity.

PMID- 9529049
TI  - Toxoplasma gondii triggers granulocyte-dependent cytokine-mediated lethal shock
      in D-galactosamine-sensitized mice.
AB  - To investigate the capacity of Toxoplasma gondii to induce cytokine-mediated
      toxicity, we employed a murine model of lethal shock in which hypersensitivity to
      microbial toxins is induced by D-galactosamine (D-Gal). Animals injected with D
      Gal and tachyzoite lysate died within 12 to 24 h, whereas administration of D-Gal
      or lysate alone was nonlethal. Analyses of plasma cytokines revealed peaks of
      tumor necrosis factor (TNF) alpha and interleukin-12 (IL-12) 1 and 3 to 5 h after
      injection, respectively, and gradually rising levels of gamma interferon (IFN
      gamma) continuing until death. Nitric oxide (NO) levels in serum paralleled IFN
      gamma production. Transaminase assays revealed elevated levels of liver
      associated enzymes in sera of lethally injected mice, indicating severe hepatic
      damage. Depletion of IL-12, TNF, IFN-gamma, and NO rescued mice from the lethal
      effect of antigen (Ag) and D-Gal. T-cell-deficient animals remained sensitive to
      D-Gal and lysate, suggesting that T lymphocytes do not contribute to the
      response. Nevertheless, monoclonal antibody (MAb)-mediated granulocyte depletion
      completely abrogated D-Gal- and Ag-induced mortality and accompanying liver
      pathology. Finally, mice acutely infected with T. gondii displayed highly
      elevated NO and liver enzyme levels in serum immediately prior to death, and
      administration of anti-TNF MAb prolonged survival by approximately 24 h. Our
      results demonstrate that T. gondii induces lethal inflammatory cytokine shock in
      D-Gal-sensitized animals and suggest that a similar pathology may contribute to
      manifestations of acute toxoplasmosis.

PMID- 9529050
TI  - Intranasal administration of a meningococcal outer membrane vesicle vaccine
      induces persistent local mucosal antibodies and serum antibodies with strong
      bactericidal activity in humans.
AB  - A nasal vaccine, consisting of outer membrane vesicles (OMVs) from group B
      Neisseria meningitidis, was given to 12 volunteers in the form of nose drops or
      nasal spray four times at weekly intervals, with a fifth dose 5 months later.
      Each nasal dose consisted of 250 microg of protein, equivalent to 10 times the
      intramuscular dose that was administered twice with a 6-week interval to 11 other
      volunteers. All individuals given the nasal vaccine developed immunoglobulin A
      (IgA) antibody responses to OMVs in nasal secretions, and eight developed
      salivary IgA antibodies which persisted for at least 5 months. Intramuscular
      immunizations did not lead to antibody responses in the secretions. Modest
      increases in serum IgG antibodies were obtained in 5 volunteers who had been
      immunized intranasally, while 10 individuals responded strongly to the
      intramuscular vaccine. Both the serum and secretory antibody responses reached a
      maximum after two to three doses of the nasal vaccine, with no significant
      booster effect of the fifth dose. The pattern of serum antibody specificities
      against the different OMV components after intranasal immunizations was largely
      similar to that obtained with the intramuscular vaccine. Five and eight vaccinees
      in the nasal group developed persistent increases in serum bactericidal titers to
      the homologous meningococcal vaccine strain expressing low and high levels,
      respectively, of the outer membrane protein Opc. Our results indicate that
      meningococcal OMVs possess the structures necessary to initiate systemic as well
      as local mucosal immune responses when presented as a nasal vaccine. Although the
      serum antibody levels were less conspicuous than those after intramuscular
      vaccinations, the demonstration of substantial bactericidal activity indicates
      that a nonproliferating nasal vaccine might induce antibodies of high functional
      quality.

PMID- 9529051
TI  - An essential role for gamma interferon in innate resistance to Shigella flexneri
      infection.
AB  - Shigella spp. are the major cause of bacillary dysentery worldwide. To identify
      immune effectors associated with protection of the naive host during infection,
      the susceptibility to pulmonary Shigella infection of each of various mouse
      strains that have a targeted deletion in a specific aspect of the immune system
      was evaluated. Our results demonstrate that mice deficient in gamma interferon
      are 5 orders of magnitude more susceptible to Shigella than are wild-type mice,
      whereas mice deficient in B and T lymphocytes or in T lymphocytes alone exhibit
      no difference in susceptibility. Significantly lower numbers of shigellae were
      recovered from immunocompetent compared with gamma-interferon-deficient mice
      after infection. While immunocompetent mice were able to clear a sublethal
      Shigella inoculum by day 5 postinfection, progressively increasing numbers of
      shigellae were cultured from the lungs of gamma interferon-deficient mice over
      the same period. Histopathology of the lungs from immunocompetent mice infected
      with a sublethal Shigella inoculum showed mild inflammatory changes, whereas the
      lungs from gamma interferon-deficient mice demonstrated progressively worsening
      acute bronchiolitis with ulceration. Further, the time to death in gamma
      interferon-deficient mice correlates inversely with the size of the Shigella
      inoculum. To identify the cellular source of gamma interferon, we infected SCID
      mice, T-cell-receptor-deficient mice, beige mice (a mouse strain deficient in
      natural killer [NK] cell activity), and mice depleted of NK cells using anti
      asialo-GM1. Each NK cell-deficient mouse strain exhibited a 10-fold-greater
      susceptibility to Shigella infection than immunocompetent mice. To test the
      protective effects of gamma interferon in vitro, survival of intracellular
      Shigella was examined in primary macrophages from wild-type mice, primary
      macrophages from gamma interferon-deficient mice, a macrophage cell line, and a
      fibroblast cell line. Following activation with gamma interferon, each cell type
      eradicated intracellular Shigella, while nonactivated macrophages fostered
      Shigella replication and nonactivated fibroblast cells fostered both Shigella
      replication and intercellular spread. Taken together, these data establish that
      NK cell-mediated gamma interferon is essential to resistance following primary
      Shigella infection.

PMID- 9529052
TI  - Immune responses of specific-pathogen-free mice to chronic Helicobacter pylori
      (strain SS1) infection.
AB  - A model permitting the establishment of persistent Helicobacter pylori infection
      in mice was recently described. To evaluate murine immune responses to H. pylori
      infection, specific-pathogen-free Swiss mice (n = 50) were intragastrically
      inoculated with 1.2 x 10(7) CFU of a mouse-adapted H. pylori isolate (strain
      SS1). Control animals (n = 10) received sterile broth medium alone. Animals were
      sacrificed at various times, from 3 days to 16 weeks postinoculation (p.i.).
      Quantitative culture of gastric tissue samples from inoculated mice demonstrated
      bacterial loads of 4.0 x 10(4) to 8 x 10(6) CFU per g of tissue in the animals.
      Infected mice had H. pylori-specific immunoglobulin M (IgM) and IgG antibodies in
      serum (at day 3 p.i.) and IgG and IgA antibodies in their gastric contents (weeks
      4 and 16 p.i.) and saliva (week 16 p.i.). Mucosal IgM antibodies were not
      detected. Histological examination of the gastric mucosae from control and
      infected mice revealed mild chronic gastritis, characterized by the presence of
      polymorphoneutrophil cell infiltrates and submucosal lymphoid aggregates, in
      infected animals at 16 weeks p.i. Differences in the quantities of IgG1 and IgG2a
      subclass antibodies detected in the sera of mouse strains (Swiss, BALB/c, and
      C57BL/6) infected by H. pylori suggested that host factors influence the immune
      responses induced against this bacterium in the host. In conclusion, immune
      responses to H. pylori infection in mice, like those in chronically infected
      humans, appear to be ineffective in resolving the infection.

PMID- 9529053
TI  - Molecular cloning and sequencing of three granulocytic Ehrlichia genes encoding
      high-molecular-weight immunoreactive proteins.
AB  - Granulocytic Ehrlichia was isolated from canine blood obtained from animals
      challenged with field-collected Ixodes scapularis and propagated in HL60 cells.
      PCR primers specific for the 16S ribosomal DNA (rDNA) of the Ehrlichia genogroup
      comprising E. equi, E. phagocytophila, and the agent of human granulocytic
      ehrlichiosis (HGE) amplified DNA from extracts of these cells. Sequence analysis
      of this amplified DNA revealed that it is identical to the 16S rDNA sequence of
      the HGE agent. A genomic library was constructed with DNA from granulocytic
      Ehrlichia and screened with pooled sera from tick-challenged, granulocytic
      Ehrlichia-infected dogs. Several clones were isolated and sequenced. Three
      complete genes encoding proteins with apparent molecular masses of 100, 130, and
      160 kDa were found. The recombinant proteins reacted with convalescent-phase sera
      from dogs and human patients recovering from HGE. This approach will be useful
      for identifying candidate diagnostic and vaccine antigens for granulocytic
      ehrlichiosis and aid in the classification of genogroup members.

PMID- 9529054
TI  - The N-terminal part of the enzyme component (C2I) of the binary Clostridium
      botulinum C2 toxin interacts with the binding component C2II and functions as a
      carrier system for a Rho ADP-ribosylating C3-like fusion toxin.
AB  - The binary actin-ADP-ribosylating Clostridium botulinum C2 toxin consists of the
      enzyme component C2I and the binding component C2II, which are separate proteins.
      The active component C2I enters cells through C2II by receptor-mediated
      endocytosis and membrane translocation. The N-terminal part of C2I (C2IN), which
      consists of 225 amino acid residues but lacks ADP-ribosyltransferase activity,
      was identified as the C2II contact site. A fusion protein (C2IN-C3) of C2IN and
      the full-length C3-like ADP-ribosyltransferase from Clostridium limosum was
      constructed. The fusion protein C2IN-C3 ADP-ribosylated Rho but not actin in CHO
      cell lysates. Together with C2II, C2IN-C3 induced complete rounding up of CHO and
      HeLa cells after incubation for 3 h. No cell rounding was observed without C2II
      or with the original C3-like transferase from C. limosum. The data indicate that
      the N-terminal 225 amino acid residues of C2I are sufficient to cause the
      cellular uptake of C. limosum transferase via the binding component of C2II,
      thereby increasing the cytotoxicity of the C3-like exoenzyme several hundred
      fold.

PMID- 9529055
TI  - Characterization of a strain of Chlamydia pneumoniae isolated from a coronary
      atheroma by analysis of the omp1 gene and biological activity in human
      endothelial cells.
AB  - Chlamydia pneumoniae is a respiratory pathogen that has been associated with
      chronic inflammatory diseases such as asthma and atherosclerosis. Recent
      isolation of C. pneumoniae from human carotid and coronary atheromas provides
      additional support for a role of this organism in atherogenesis. We characterized
      the coronary strain C. pneumoniae A-03 by sequence analysis of the major outer
      membrane protein gene (omp1). In addition, the in vitro activities of A-03 and
      three respiratory strains of C. pneumoniae (BAL-16, TW-183, and T-2634) were
      examined in infected human umbilical vein endothelial cells (HUVEC) by analysis
      of the production of interleukin-8 (IL-8), monocyte chemotactic protein 1 (MCP
      1), and soluble intercellular cell adhesion molecule 1 (sICAM-1). Sequence
      analysis of omp1 of C. pneumoniae A-03, compared to prototype strains TW-183 and
      AR-39, revealed five nucleotide changes resulting in nonsynonymous codons. Of
      interest was a nonconservative amino acid substitution (Ser to Pro) in position
      61 of variable segment 1. In vitro, the extent of MCP-1, IL-8, and sICAM-1
      production was dependent on the C. pneumoniae strain examined at low
      multiplicities of infection following 24 h of incubation. Strain A-03 displayed
      the lowest stimulatory activity in infected HUVEC, while T-2634 induced the
      highest levels of MCP-1, IL-8, and sICAM-1 among all strains examined. Heat
      inactivated C. pneumoniae failed to stimulate production of these proteins by all
      strains tested. In contrast, only partial inhibition was observed by UV
      inactivated organisms. Results from this study demonstrate that unlike prototype
      respiratory strains of C. pneumoniae, the coronary strain A-03 displays
      divergence in the omp1 gene. In addition, the stimulation of chemokines and
      adhesion molecules involved in the recruitment of leukocytes to sites of
      inflammation by C. pneumoniae may be important in the pathogenesis of diseases
      associated with this organism, including atherosclerosis.

PMID- 9529056
TI  - Differences in the frequency of cytokine-producing cells in antigenemic and
      nonantigenemic individuals with bancroftian filariasis.
AB  - Individuals with clinical manifestations of lymphatic filariasis may be currently
      infected or not. Twenty-five individuals from a Wuchereria bancrofti-endemic area
      of Brazil were classified as being asymptomatic microfilaremic individuals,
      antigenemic individuals with clinical filariasis, or nonantigenemic individuals
      with clinical filariasis. Intracellular cytokine staining of mitogen-stimulated
      peripheral blood mononuclear cells (PBMC) showed that the frequency of either
      gamma interferon (IFN-gamma)- or interleukin-4 (IL-4)-producing cells was higher
      in the nonantigenemic individuals with clinical filariasis than in the
      asymptomatic microfilaremic individuals (geometric means, 22.1 versus 10.7% [P =
      0.02] and 2.9 versus 1.4% [P = 0.01], respectively). When the asymptomatic
      microfilaremic individuals and antigenemic individuals with clinical filariasis
      were grouped together to constitute all actively infected individuals, the
      frequency of IFN-gamma-producing cells was also lower than in the nonantigenemic
      individuals with clinical filariasis (P = 0.04). Likewise, the frequency of IL-4
      producing cells in the actively infected individuals was also lower than in the
      nonantigenemic individuals with clinical filariasis (P = 0.02). No differences in
      the frequency of IFN-gamma-, IL-4-, or IL-5-producing cells in purified CD4 T
      lymphocytes were found among the groups. These findings suggest that the presence
      of antigenemia, which is an indicator of current active infection, is closely
      associated with the frequency of IFN-gamma- and IL-4-producing cells in lymphatic
      filariasis. The differences found in the frequency of cytokine-producing cells
      among the three groups appear to be due to a subset of cells other than CD4 T
      cells.

PMID- 9529057
TI  - Cytokine involvement in immunomodulatory activity affected by Candida albicans
      mannan.
AB  - Candida albicans mannoprotein (MAN) administered intravenously to mice stimulates
      the production of splenic CD8+ effector cells which downregulate delayed
      hypersensitivity (DH) in immunized mice. Cytokine involvement in the induction
      and/or elicitation of downregulation was studied by (i) examining murine
      splenocytes qualitatively for mRNA for interleukin-2 (IL-2), IL-4, IL-10, IL
      12p40, and gamma interferon (IFN-gamma), (ii) quantitating splenocyte mRNA for IL
      12p40 by quantitative-competitive reverse transcriptase-mediated PCR, and (iii)
      measuring serum levels of IL-12p40 and IL-12p70 by capture enzyme-linked
      immunosorbent assay, each performed at selected intervals over 96 h after giving
      MAN. Further, the effect of in vivo administration of anti-IL-4 on the induction
      and elicitation of MAN-specific DH in MAN-treated mice was measured. Expression
      of IL-12p40 mRNA in the spleen was reduced to near 0 during the first 24 h but
      rebounded thereafter. Transcripts for IL-10 were present throughout the 96-h
      period, whereas those for IL-4 and IFN-gamma were either weak or undetectable
      prior to 24 to 48 h. In vivo administration of anti-IL-4 partially abrogated the
      downregulatory effect of MAN only when given at the time of MAN administration.
      Serum levels of IL-12p40, but not IL-12p70, were increased by 24 h and maximal at
      48 h. The antagonistic effect of IL-12p40 could contribute to the mechanism(s)
      for downregulation of DH. Moreover, IL-10, IL-4, and/or IFN-gamma, interacting
      with MAN-activated cells in the absence of biologically active IL-12, may induce
      the production of CD8+ downregulatory effector cells. Partial abrogation of
      downregulatory activity in animals treated with anti-IL-4 at the time of
      induction of such activity lends support to this hypothesis.

PMID- 9529058
TI  - Alterations in frequency of interleukin-2 (IL-2)-, gamma interferon-, or IL-4
      secreting splenocytes induced by Candida albicans mannan and/or monophosphoryl
      lipid A.
AB  - We have shown previously that intravenous injection of Candida albicans mannan
      (MAN) into naive mice induced CD8+ effector downregulatory cells and that such
      cells were not produced if mice were deficient in CD4+ or I-A+ cells during the
      early interval (< or =30 h) following the introduction of MAN. Moreover, the
      nonspecific biological response modifier monophosphoryl lipid A (MPL), given in
      vivo or incubated with cells in vitro, can abrogate the MAN-specific
      immunomodulatory activity. The mechanism by which the abrogation is mediated is
      unknown, but it is hypothesized to involve cytokines. Therefore, we measured the
      number of cytokine-secreting cells for the Thl cytokine interleukin-2 (IL-2) and
      the Th2 cytokine IL-4, as well as for gamma interferon (IFN-gamma), in splenocyte
      populations from MAN and/or MPL-treated mice, using an enzyme-linked immunospot
      assay designed to detect individual cytokine-secreting cells (spot-forming cells
      [SFC]). Cytokine-secreting cells were demonstrated in cell suspensions enriched
      for CD4+ cells, but no SFC could be demonstrated in populations enriched for CD8+
      cells. Both MAN and MPL, when administered to separate groups of animals,
      stimulated the production of increased numbers of cytokine-producing cells for
      each of the three cytokines tested. The response with respect to IL-4-secreting
      cells, however, was the most striking. Despite the fact that MAN and MPL
      independently caused increases in SFC to all three cytokines, when both MAN and
      MPL were administered to the same animal, all increases were reversed, and the
      numbers of SFC detected were at or below those detected in saline control
      animals. These data support the hypothesis that IL-4 is involved in MAN-specific
      immunoregulatory activities. The data also emphasize the fact that two
      immunomodulators, i.e., MAN and MPL, having similar effects when given in vivo
      independently, may be antagonistic when administered sequentially to the same
      animal.

PMID- 9529059
TI  - Endotoxin-neutralizing protein protects against endotoxin-induced endothelial
      barrier dysfunction.
AB  - Bacterial lipopolysaccharide induces tyrosine phosphorylation of paxillin, actin
      reorganization, and opening of the transendothelial paracellular pathway through
      which macromoles flux. In this study, lipid A was shown to be the bioactive
      portion of the lipopolysaccharide molecule responsible for changes in endothelial
      barrier function. We then studied whether endotoxin-neutralizing protein, a
      recombinant peptide that is derived from Limulus antilipopolysaccharide factor
      and targets lipid A, could block the effects of lipopolysaccharide on protein
      tyrosine phosphorylation, actin organization, and movement of 14C-bovine serum
      albumin across bovine pulmonary artery endothelial cell monolayers. In the
      presence of serum, a 6-h exposure to lipopolysaccharide (10 ng/ml) increased
      transendothelial 14C-albumin flux compared to the simultaneous media control.
      Coadministration of endotoxin-neutralizing protein (> or =10 ng/ml) with
      lipopolysaccharide (10 ng/ml) protected against lipopolysaccharide-induced
      barrier dysfunction. This protection was dose dependent, conferring total
      protection at endotoxin-neutralizing protein/lipopolysaccharide ratios of > or
      =10:1. Similarly, endotoxin-neutralizing protein was capable of blocking the
      lipopolysaccharide-induced endothelial cell responses that are prerequisite to
      barrier dysfunction, including tyrosine phosphorylation of paxillin and actin
      depolymerization. Finally, endotoxin-neutralizing protein cross-protected against
      lipopolysaccharide derived from diverse gram-negative bacteria. Thus, endotoxin
      neutralizing protein offers a novel therapeutic intervention for the vascular
      endothelial dysfunction of gram-negative sepsis and its attendant endotoxemia.

PMID- 9529060
TI  - Elastase is the only human neutrophil granule protein that alone is responsible
      for in vitro killing of Borrelia burgdorferi.
AB  - Phagocytosis of Borrelia burgdorferi by human polymorphonuclear leukocytes
      triggers oxygen-dependent and -independent mechanisms of potentially cidal
      outcome. Nevertheless, no factor or process has yet been singled out as being
      borreliacidal. We have studied the B. burgdorferi-killing ability of the
      myeloperoxidase-H2O2-chloride system and that of primary and secondary granule
      components in an in vitro assay. We found that neither secondary granule acid
      extracts nor the chlorinating system could kill these microorganisms, while
      primary granule extracts were effective. The Borrelia-killing factor was purified
      to homogeneity and demonstrated to be elastase. Its cidal activity was found to
      be independent of its proteolytic activity.

PMID- 9529062
TI  - The protective effects of lactoferrin feeding against endotoxin lethal shock in
      germfree piglets.
AB  - The unique germfree, colostrum-deprived, immunologically "virgin" piglet model
      was used to evaluate the ability of lactoferrin (LF) to protect against lethal
      shock induced by intravenously administered endotoxin. Piglets were fed LF or
      bovine serum albumin (BSA) prior to challenge with intravenous Escherichia coli
      lipopolysaccharide (LPS), and temperature, clinical symptoms, and mortality were
      tracked for 48 h following LPS administration. Prefeeding with LF resulted in a
      significant decrease in piglet mortality compared to feeding with BSA (16.7
      versus 73.7% mortality, P < 0.001). Protection against the LPS challenge by LF
      was also correlated with both resistance to induction of hypothermia by endotoxin
      and an overall increase in wellness, as quantified by a toxicity score developed
      for these studies. In vitro studies using a flow cytometric assay system
      demonstrated that LPS binding to porcine monocytes was inhibited by LF in a dose
      dependent fashion, suggesting that the mechanism of LF action in vivo may be
      inhibition of LPS binding to monocytes/macrophages and, in turn, prevention of
      induction of monocyte/macrophage-derived inflammatory-toxic cytokines.

PMID- 9529061
TI  - Defects in type III secretion correlate with internalization of Pseudomonas
      aeruginosa by epithelial cells.
AB  - Previous characterization of Pseudomonas aeruginosa clinical isolates has
      demonstrated an inverse correlation between cytotoxicity and internalization by
      epithelial cells. To further investigate this relationship, we tested PA103, a
      cytotoxic P. aeruginosa strain, and 33 isogenic noncytotoxic transposon mutants
      for internalization by Madin-Darby canine kidney cells. The majority of the
      mutants were not internalized, demonstrating that an inverse correlation between
      cytotoxicity and bacterial uptake by epithelial cells is not absolute. Six of the
      noncytotoxic mutants, however, demonstrated measurable levels of internalization
      by standard aminoglycoside exclusion assays even though internalization of wild
      type strain PA103 was not detectable. All six had evidence of protein secretion
      defects involving two proteins, a 40-kDa protein and a 32-kDa protein. These
      proteins, designated PepB (for Pseudomonas exoprotein B) and PepD, respectively,
      each had characteristics of type III transported proteins. In addition,
      nucleotide sequencing studies demonstrated that PepB and PepD are homologs of
      YopB and YopD, respectively, type III secreted proteins of Yersinia spp.
      necessary for the translocation of effector molecules into the cytoplasmic
      compartment of eukaryotic cells. Thus, while many mutations in PA103 result in
      loss of cytotoxicity without an appreciable increase in internalization, defects
      in transport of type III secretion proteins PepB and PepD correlate with both
      loss of cytotoxicity and gain of internalization. These results are consistent
      with type III secretion of an inhibitor of internalization that requires PepB and
      PepD for translocation into the host cell.

PMID- 9529063
TI  - M protein of the group A Streptococcus binds to the seventh short consensus
      repeat of human complement factor H.
AB  - Streptococcus pyogenes evades complement by binding the complement-regulatory
      protein factor H (fH) via the central conserved C-repeat region of M protein.
      However, the corresponding binding region within fH has not previously been
      precisely localized. fH is composed of 20 conserved modules called short
      consensus repeats (SCRs), each of which contains approximately 60 amino acids. A
      series of fH truncated and deletion mutants were prepared, and their interaction
      with M6 protein was examined. The M protein binding site was initially localized
      to SCRs 6 to 15 as demonstrated by ligand dot blotting, chemical cross-linking,
      and enzyme-linked immunosorbent assay. SCR 7 was then shown to contain the M
      protein binding site, as a construct consisting of the first seven SCRs bound M
      protein but a construct containing the first six SCRs did not bind. In addition,
      deletion of SCR 7 from full-length fH abolished binding to M protein. SCR 7 is
      known to contain a heparin binding domain, and binding of fH to M6 protein was
      almost totally inhibited in the presence of 400 U of heparin per ml. These
      results localize the M6 protein binding site of fH to SCR 7 and indicate that it
      is in close proximity to the heparin binding site.

PMID- 9529064
TI  - Mutation of invH, but not stn, reduces Salmonella-induced enteritis in cattle.
AB  - The induction of secretory and inflammatory responses in calves by Salmonella
      typhimurium and Salmonella dublin strains was compared, and the effects of
      mutations in the invH and stn genes were assessed. S. typhimurium induced greater
      secretory and inflammatory responses than S. dublin in bovine ileal loops,
      despite the fact that these serotypes were recovered from bovine ileal mucosa in
      comparable numbers (P. R. Watson, S. M. Paulin, A. P. Bland, P. W. Jones, and T.
      S. Wallis, Infect. Immun. 63:2743-2754, 1995). These results implicate serotype
      specific factors other than, or in addition to, intestinal invasion in the
      induction of enteritis. The secretory and inflammatory responses induced by S.
      typhimurium and S. dublin in bovine ligated ileal loops were not significantly
      altered by mutation of stn, which suggests that stn does not have a major role in
      Salmonella-induced enteritis. The invH mutation significantly reduced the
      secretory and inflammatory responses induced in bovine ileal loops, and this
      correlated with a reduction in the severity of enteritis following oral
      inoculation of calves. The attenuation associated with the invH mutation did not
      appear to be due to an increased susceptibility to the innate host defense
      mechanisms, because the resistance of S. typhimurium to the bactericidal action
      of either bovine polymorphonuclear leukocytes or bovine serum was not
      significantly altered. However, lysis of macrophages following infection with S.
      typhimurium was significantly reduced by the invH mutation. The invH mutation
      prevented the normal secretion of several proteins, including SipC, by S.
      typhimurium, indicating that the function of the inv-spa-encoded type III protein
      secretion system was disrupted. Taken together, these observations implicate inv
      spa-dependent effectors in mediation of Salmonella-induced enteritis in cattle.
      Clearly, however, other undefined serotype-specific virulence factors are also
      involved in Salmonella-induced enteritis.

PMID- 9529065
TI  - Adherence of Streptococcus pneumoniae to respiratory epithelial cells is
      inhibited by sialylated oligosaccharides.
AB  - To study carbohydrate-mediated adherence of Streptococcus pneumoniae to the human
      airway, we measured binding of live S. pneumoniae organisms to a cultured cell
      line derived from the lining of the conjunctiva and to primary monolayers of
      human bronchial epithelial cells in the presence and absence of oligosaccharide
      inhibitors. Both encapsulated and nonencapsulated strains of S. pneumoniae grown
      to mid-logarithmic phase in suspension culture adhered to cultured primary
      respiratory epithelial cells and the conjunctival cell line. Adherence of nine
      clinically prevalent S. pneumoniae capsular types studied was inhibited
      preferentially by sialylated oligosaccharides that terminate with the
      disaccharide NeuAc alpha2-3(or 6)Galbeta1. Adherence of some strains also was
      weakly inhibited by oligosaccharides that terminate with lactosamine (Galbeta1
      4GlcNAcbeta1). When sialylated oligosaccharides were covalently coupled to human
      serum albumin at a density of approximately 20 oligosaccharides per molecule of
      protein, the molar inhibitory potency of the oligosaccharide inhibitor was
      enhanced 500-fold. The above-mentioned experiments reveal a previously unreported
      dependence upon sialylated carbohydrate ligands for adherence of S. pneumoniae to
      human upper airway epithelial cells. Enhanced inhibitory potencies of polyvalent
      over monovalent forms of oligosaccharide inhibitors of adherence suggest that the
      putative adhesin(s) that recognizes the structure NeuAc alpha2-3(or 6)Galbeta1 is
      arranged on the bacterial surface in such a manner that it may be cross-linked by
      oligosaccharides covalently linked to human serum albumin.

PMID- 9529066
TI  - Immunochemical characterization of the MPB70/80 and MPB83 proteins of
      Mycobacterium bovis.
AB  - MPB70 and MPB80 (MPB70/80) and MPB83 are closely related antigens which are
      highly expressed in Mycobacterium bovis. MPB70/80 are soluble secreted antigens,
      while MPB83 is an exported lipoprotein associated with the bacterial surface. In
      the present study, these antigens had different mobilities in sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis under reducing and nonreducing
      conditions. These differences may be explained by the fact that MPB70 and MPB83
      both have two internal cysteine residues which would create ring structures by
      disulfide bonding. We analyzed the structures of MPB70/80 and MPB83 by using
      monoclonal antibodies (MAbs) raised against bovine purified protein derivative or
      whole M. bovis cells. MAb 1-5C reacted specifically with MPB70 and MPB80, and MAb
      MBS43 reacted specifically with MPB83, while the other antibodies, including
      several previously described MAbs, bound all three antigens. MAbs and polyclonal
      antibodies reacted strongly with reduced protein and less well with nonreduced
      protein, indicating involvement of linear epitopes. Epitopes of MAbs Bov-1, 2-6B,
      1-5C, and 1-1D were mapped by using synthetic peptides of MPB70. Sequence
      comparison showed the peptide with the 1-5C-reactive epitope to have three
      residues different from those in the homologous region of MPB83. Exchanges of A
      for S in position 112 or Q for E in position 116 abolished the reactivity of MAb
      1-5C. Polyclonal rabbit antibodies to native purified MPB70 reacted strongly with
      peptides 6, 7, and 8 of the N-terminal half of mature MPB70. Cattle sera of
      experimentally M. bovis-infected animals recognized a broader spectrum of
      peptides. These findings indicate that there is diagnostic potential for these
      proteins and that there is also a possible role for antibodies in elucidation of
      the host-mycobacterium relationship involving a surface-bound and exposed
      lipoprotein, MPB83, and its highly homologous soluble secreted MPB70/80
      counterparts.

PMID- 9529067
TI  - Pseudomonas aeruginosa invasion and cytotoxicity are independent events, both of
      which involve protein tyrosine kinase activity.
AB  - Pseudomonas aeruginosa clinical isolates exhibit invasive or cytotoxic
      phenotypes. Cytotoxic strains acquire some of the characteristics of invasive
      strains when a regulatory gene, exsA, that controls the expression of several
      extracellular proteins, is inactivated. exsA mutants are not cytotoxic and can be
      detected within epithelial cells by gentamicin survival assays. The purpose of
      this study was to determine whether epithelial cell invasion precedes and/or is
      essential for cytotoxicity. This was tested by measuring invasion (gentamicin
      survival) and cytotoxicity (trypan blue staining) of PA103 mutants deficient in
      specific exsA-regulated proteins and by testing the effect of drugs that inhibit
      invasion for their effect on cytotoxicity. A transposon mutant in the exsA
      regulated extracellular factor exoU was neither cytotoxic nor invasive.
      Furthermore, several of the drugs that inhibited invasion did not prevent
      cytotoxicity. These results show that invasion and cytotoxicity are mutually
      exclusive events, inversely regulated by an exsA-encoded invasion inhibitor(s).
      Both involve host cell protein tyrosine kinase (PTK) activity, but they differ in
      that invasion requires Src family tyrosine kinases and calcium-calmodulin
      activity. PTK inhibitor drugs such as genistein may have therapeutic potential
      through their ability to block both invasive and cytotoxicity pathways via an
      action on the host cell.

PMID- 9529068
TI  - Effect of group A streptococcal cysteine protease on invasion of epithelial
      cells.
AB  - Cysteine protease of group A streptococci (GAS) is considered an important
      virulence factor. However, its role in invasiveness of GAS has not been
      investigated. We demonstrated in this study that two strains of protease
      producing GAS had the ability to invade A-549 human respiratory epithelial cells.
      Isogenic protease mutants were constructed by using integrational plasmids to
      disrupt the speB gene and confirmed by Southern hybridization and Western
      immunoblot analyses. No extracellular protease activity was produced by the
      mutants. The mutants had growth rates similar to those of the wild-type strains
      and produced normal levels of other extracellular proteins. When invading A-549
      cells, the mutants had a two- to threefold decrease in activity compared to that
      of the wild-type strains. The invasion activity increased when the A-549 cells
      were incubated with purified cysteine protease and the mutant. However, blockage
      of the cysteine protease with a specific cysteine protease inhibitor, E-64,
      decreased the invasion activity of GAS. Intracellular growth of GAS was not found
      in A-549 cells. The presence or absence of protease activity did not affect the
      adhesive ability of GAS. These results suggested that streptococcal cysteine
      protease can enhance the invasion ability of GAS in human respiratory epithelial
      cells.

PMID- 9529069
TI  - Molecular analysis of Shiga toxigenic Escherichia coli O111:H- proteins which
      react with sera from patients with hemolytic-uremic syndrome.
AB  - Western blot analysis was used to assess the reactivity of convalescent-phase
      sera from patients who were associated with an outbreak of hemolytic-uremic
      syndrome (HUS) caused by fermented sausage contaminated with Shiga toxin
      producing Escherichia coli (STEC). The predominant STEC isolated from HUS
      patients belonged to serotype O111:H-, and reactivity to O111:H- whole-cell
      lysates, treated or untreated with proteinase K, was examined. As expected, all
      five serum samples demonstrated a marked anti-lipopolysaccharide response, but
      several protein bands were also immunoreactive, particularly one with an apparent
      size of 94 kDa. One convalescent-phase serum sample was subsequently used to
      screen an O111:H- cosmid bank and 2 of 900 cosmid clones were found to be
      positive, both of which contained a similar DNA insert. Western blot analysis of
      one of these clones identified three major immunoreactive protein bands of
      approximately 94, 70, and 50 kDa. An immune response to the three proteins was
      detectable with all five convalescent-phase serum samples but not with healthy
      human serum. Immunoreactive 94- and 50-kDa species were produced by a deletion
      derivative of the cosmid containing a 7-kb STEC DNA insert. Sequence analysis of
      this region indicated that it is part of the locus for enterocyte effacement,
      including the eaeA gene which encodes intimin. The deduced amino acid sequence of
      the O111:H- intimin was 88.6% identical to intimin from O157:H7 STEC, and the
      most divergent region was the 200 residues at the carboxyl terminus, which were
      only 75% identical. Such variation may be antigenically significant as serum from
      a HUS patient infected only with the O111:H- STEC reacted with intimin from an
      enteropathogenic E. coli O111 strain, as well as several other eaeA-positive STEC
      isolates, but not with an eaeA-positive STEC belonging to serotype O157:H-. Sera
      from two of the other HUS patients also failed to react with intimin from this
      latter strain. However, intimin from O157:H- STEC did react with serum from a
      patient infected with both O111:H- and O157:H- STEC.

PMID- 9529071
TI  - Identification of a gene involved in assembly of Actinomyces naeslundii T14V type
      2 fimbriae.
AB  - The nucleotide sequence of the Actinomyces naeslundii T14V type 2 fimbrial
      structural subunit gene, fimA, and the 3' flanking DNA region was determined. The
      fimA gene encoded a 535-amino-acid precursor subunit protein (FimA) which
      included both N-terminal leader and C-terminal cell wall sorting sequences. A
      second gene, designated orf365, that encoded a 365-amino-acid protein which
      contained a putative transmembrane segment was identified immediately 3' to fimA.
      Mutants in which either fimA or orf365 was replaced with a kanamycin resistance
      gene did not participate in type 2 fimbriae-mediated coaggregation with
      Streptococcus oralis 34. Type 2 fimbrial antigen was not detected in cell
      extracts of the fimA mutant by Western blotting with anti-A. naeslundii type 2
      fimbrial antibody, but the subunit protein was detected in extracts of the orf365
      mutant. The subunit protein detected in this mutant also was immunostained by an
      antibody raised against a synthetic peptide representing the C-terminal 20 amino
      acid residues of the predicted FimA. The antipeptide antibody reacted with FimA
      isolated from the recombinant Escherichia coli clone containing fimA but did not
      react with purified type 2 fimbriae in extracts of the wild-type strain. These
      results indicate that synthesis of type 2 fimbriae in A. naeslundii T14V may
      involve posttranslational cleavage of both the N-terminal and C-terminal peptides
      of the precursor subunit and also the expression of orf365.

PMID- 9529072
TI  - Sequence analysis of the mip gene of the soilborne pathogen Legionella
      longbeachae.
AB  - To understand the basis of pathogenesis by Legionella longbeachae serogroup 1,
      the importance of the Mip protein in this species was examined. Amino-terminal
      analysis of the purified, cloned L. longbeachae serogroup 1 ATCC 33462 Mip
      protein confirmed that the cloned gene protein was expressed and processed in an
      Escherichia coli background. DNA sequence analysis of plasmid pIMVS27, containing
      the entire L. longbeachae serogroup 1 mip gene, revealed a high degree of
      homology to the mip gene of Legionella pneumophila serogroup 1, 76% homology at
      the DNA level and 87% identity at the amino acid level. Primer extension analysis
      determined that the start site of transcription was the same for both species,
      with some differences observed for the -10 and -35 promoter regions. Primers
      designed from the mip gene sequence obtained for L. longbeachae serogroup 1 ATCC
      33462 were used to amplify the mip genes from L. longbeachae serogroup 2 ATCC
      33484 and an Australian clinical isolate of L. longbeachae serogroup 1 A5H5. The
      mip gene from A5H5 was 100% identical to the type strain sequence. The serogroup
      2 strain of L. longbeachae differed by 2 base pairs in third-codon positions.
      Allelic exchange mutagenesis was used to generate an isogenic mip mutant in ATCC
      33462 and strain A5H5. The ATCC mip mutant was unable to infect a strain of
      Acanthamoebae sp. both in liquid and in a potting mix coculture system, while the
      A5H5 mip mutant behaved in a manner siilar to that of L. pneumophila serogroup 1,
      i.e., it displayed a reduced capacity to infect and multiply within
      Acanthamoebae. To determine if this mutation resulted in reduced virulence in the
      guinea pig animal model, the A5H5 mip mutant and its parent strain were assessed
      for their abilities to establish an infection after aerosol exposure. Unlike the
      virulent parent strain, the mutant strain did not kill any animals under two
      different dose regimes. The data indicate that the Mip protein plays an important
      role in the intracellular life cycle of L. longbeachae serogroup 1 species and is
      required for full virulence.

PMID- 9529070
TI  - Evolution of the primary immune response to Histoplasma capsulatum in murine
      lung.
AB  - Histoplasma capsulatum induces a cell-mediated immune response in the lungs and
      lymphoid organs of mammals. In this study, we analyzed the progression of the
      cytokine and inflammatory reactions in the lungs of mice infected intranasally
      with H. capsulatum. We measured cytokine mRNA levels and determined the
      inflammatory cell populations during the active phase of infection (<3 weeks).
      Transcription of genes encoding interleukin-2 (IL-2), IL-4, and IL-12 and gamma
      interferon (IFN-gamma) was detectable as early as day 3 of infection, whereas a
      signal for IL-10 was never observed. Competitive PCR analysis demonstrated that
      enhanced expression of IL-12 mRNA was observed by day 3 and that expression of
      mRNA for IL-2 and IFN-gamma progressively increased from day 5 to day 10. All
      levels declined by day 14. Analysis of the inflammatory response revealed an
      initial elevation in myeloid cells (Mac-1+) and natural killer (NK) cells
      followed by a rise in T cells, predominantly CD4+ cells. Since IFN-gamma is a key
      factor in host defense, we performed cytoplasmic staining to determine the cell
      populations that produced this cytokine. The hierarchy of synthesis was CD4+ >
      CD8+ > NK cells. Thus, H. capsulatum provokes an orderly modulation of the
      inflammatory and cytokine responses in murine lungs.

PMID- 9529073
TI  - Baculovirus merozoite surface protein 1 C-terminal recombinant antigens are
      highly protective in a natural primate model for human Plasmodium vivax malaria.
AB  - A successful anti-blood stage malaria vaccine trial based on a leading vaccine
      candidate, the major merozoite surface antigen-1 (MSP1), is reported here. The
      trial was based on Plasmodium cynomolgi, which is a primate malaria parasite
      which is highly analogous to the human parasite Plasmodium vivax, in its natural
      host, the toque monkey, Macaca sinica. Two recombinant baculovirus-expressed P.
      cynomolgi MSP1 proteins, which are analogous to the 42- and 19-kDa C-terminal
      fragments of P. falciparum MSP1, were tested by immunizing three groups of three
      animals each with either p42, p19, or both together. The vaccines were delivered
      subcutaneously in three doses at 4-week intervals with complete and incomplete
      Freund's adjuvants. Very high antibody titers were obtained against both
      vaccinating antigens as measured by enzyme-linked immunosorbent assay (10[6] and
      above) and against whole parasites as measured by indirect immunofluorescence
      assay (>10[5]), achieving, in most animals, about a 10-fold increase from the
      first to the last immunization. A blood stage challenge with P. cynomolgi
      parasites led, in three adjuvant-treated and three naive control animals, to
      blood infections which were patent for at least 44 days, reaching peak densities
      of 0.6 and 3.8%, respectively. In contrast, all except one of the nine animals in
      the three vaccinated groups were highly protected, showing either no parasitemia
      at all or transient parasitemias which were patent for only 1 or 2 days. When the
      three p19-vaccinated monkeys were rechallenged 6 months later, the protective
      efficacy was unchanged. The success of this trial, and striking analogies of this
      natural host-parasite system with human P. vivax malaria, suggests that it could
      serve as a surrogate system for the development of a human P. vivax malaria
      vaccine based on similar recombinant analogs of the P. vivax MSP1 antigen.

PMID- 9529074
TI  - Inhibition of the production of anti-OspA borreliacidal antibody with T cells
      from hamsters vaccinated against Borrelia burgdorferi.
AB  - The serious morbidity associated with Lyme borreliosis has focused considerable
      effort on the development of a comprehensive vaccine for protection against
      infection with Borrelia burgdorferi. Induction of borreliacidal antibody by
      vaccination or infection has been shown to correlate with protection of humans
      and animals against infection with the Lyme spirochete. In this report, we showed
      that high levels of borreliacidal antibody (titer of 1,280) were produced in
      vitro when T and B cells from hamsters 14 days after vaccination were incubated
      with macrophages and B. burgdorferi. By contrast, T and B cells from hamsters 7
      or 21 days after vaccination failed to initiate production of borreliacidal
      activity. Furthermore, the T cells from hamsters 7 or 21 days after vaccination
      inhibited the in vitro production of borreliacidal antibody when cocultured with
      T and B cells obtained from hamsters 14 days after vaccination. When cell-free
      supernatants from the suspensions of T and B cells from hamsters 14 days after
      vaccination were absorbed with recombinant OspA, they lost nearly all
      borreliacidal activity. The removal of anti-OspA antibody resulted in a decrease
      in borreliacidal titer from 1,280 to less than 4. These results demonstrate that
      T cells from vaccinated animals can prevent a sustained production of protective
      borreliacidal antibody.

PMID- 9529075
TI  - Enhanced protective antibody responses to PspA after intranasal or subcutaneous
      injections of PspA genetically fused to granulocyte-macrophage colony-stimulating
      factor or interleukin-2.
AB  - Antibody to pneumococcal surface protein A (PspA) has been shown to be protective
      for Streptococcus pneumoniae infections in mice. In an attempt to define a model
      for inducing protective antibody to PspA in the absence of adjuvant, we designed
      two genetic fusions, PspA-interleukin-2 [IL-2]) and PspA-granulocyte-macrophage
      colony-stimulating factor (GM-CSF). These constructs maintained high cytokine
      function in vitro, as tested by their activity on IL-2 or GM-CSF-dependent cell
      lines. While intranasal immunization with PspA induced no detectable anti-PspA
      response, both PspA-IL-2 and PspA-GM-CSF stimulated high immunoglobulin G1 (IgG1)
      antibody responses. Interestingly, only the PspA-IL-2, not the PspA-GM-CSF,
      construct stimulated IgG2a antibody responses, suggesting that this construct
      directed the response along a TH1-dependent pathway. Comparable enhancement of
      the anti-PspA response with similar isotype profiles was observed after
      subcutaneous immunization as well. The enhancement observed with PspA-IL-2 was
      dependent on IL-2 activity in that it was not seen in IL-2 receptor knockout
      mice, while PspA in alum induced high-titer antibody in these mice. The antibody
      was tested for its protective activity in a mouse lethality model using S.
      pneumoniae WU-R2. Passive transfer of 1:90 dilutions of sera from mice immunized
      with PspA-IL-2 and PspA-GM-CSF elicited protection of CBA/N mice against
      intravenous challenge with over 170 50% lethal doses of capsular type 3 strain
      WU2. Only 0.17 microg or less of IgG antibody to PspA was able to provide passive
      protection against otherwise fatal challenge with S. pneumoniae. The data
      demonstrate that designing protein-cytokine fusions may be a useful approach for
      mucosal immunization and can induce high-titer systemic protective antibody
      responses.

PMID- 9529076
TI  - A new member of the S-layer protein family: characterization of the crs gene from
      Campylobacter rectus.
AB  - Strains of the periodontal pathogen Campylobacter rectus express a 150- to 166
      kDa protein on their cell surface. This protein forms a paracrystalline lattice,
      called the surface layer (S-layer), on the outer membrane of this gram-negative
      bacterium. To initiate a genetic analysis of the function of the S-layer in the
      pathogenesis of C. rectus, we have cloned and characterized its gene. The S-layer
      gene (crs) from C. rectus 314 encodes a cell surface protein which does not have
      a cleaved signal peptide at its amino terminus. Although the amino acid sequence
      deduced from the crs gene has 50% identity with the amino-terminal 30 amino acids
      of the four S-layer proteins from Campylobacter fetus, the similarity decreases
      to less than 16% over the rest of the protein. Thus, the crs gene from C. rectus
      encodes a novel S-layer protein whose precise role in pathogenesis may differ
      from that of S-layer proteins from other organisms. Southern and Northern blot
      analyses with probes from different segments of the crs gene indicate that the S
      layer gene is a single-copy, monocistronic gene in C. rectus. RNA end mapping and
      sequence analyses were used to define the crs promoter; there is an exact match
      to the Escherichia coli -10 promoter consensus sequence but only a weak match to
      the -35 consensus element. Southern blots of DNA from another strain of C.
      rectus, ATCC 33238, demonstrated that the crs gene is also present in that strain
      but that there are numerous restriction fragment length polymorphisms in the
      second half of the gene. This finding suggests that the carboxy halves of the S
      layer proteins from strains 314 and 33238 differ. It remains to be determined
      whether the diversities in sequence are reflected in functional or antigenic
      differences important for the pathogenesis of different C. rectus isolates.

PMID- 9529077
TI  - Vaccination with plasmid DNA encoding mycobacterial antigen 85A stimulates a CD4+
      and CD8+ T-cell epitopic repertoire broader than that stimulated by Mycobacterium
      tuberculosis H37Rv infection.
AB  - Vaccination of mice with plasmid DNA carrying the gene for the major secreted
      mycobacterial antigen 85A (Ag85A) from Mycobacterium tuberculosis is a powerful
      technique for generating robust specific Thl helper T-cell responses, CD8+
      mediated cytotoxicity, and protection against M. tuberculosis challenge (K.
      Huygen et al., Nat. Med. 2:893-898, 1996). We have now analyzed in more detail
      the antigen-specific immune CD4+- and CD8+-T-cell responses induced in BALB/c
      mice vaccinated with Ag85A DNA and have compared these responses to those
      generated by intravenous infection with M. tuberculosis. T-cell-epitope mapping,
      as measured by interleukin-2 and gamma interferon secretion from splenic T cells
      restimulated in vitro with synthetic 20-mer peptides spanning the complete mature
      sequence of Ag85A, demonstrated that DNA vaccination stimulated a stronger and
      broader T-cell response than did M. tuberculosis infection. Moreover, elevated
      cytotoxic T lymphocyte (CTL) activity against Ag85A-transfected and peptide
      pulsed P815 target cells could be generated exclusively by vaccination with
      plasmid DNA, not following M. tuberculosis infection. By using DNA vaccination,
      three Ag85A CTL epitopes with predicted major histocompatibility complex class I
      binding motifs were defined. One of them was previously reported as a dominant,
      promiscuously recognized T-cell epitope in healthy humans with primary
      infections. These data strengthen the potential of DNA vaccination with respect
      to inducing antituberculous immunity in humans.

PMID- 9529078
TI  - Phlebotomus papatasi saliva inhibits protein phosphatase activity and nitric
      oxide production by murine macrophages.
AB  - Leishmania parasites, transmitted by phlebotomine sand flies, are obligate
      intracellular parasites of macrophages. The sand fly Phlebotomus papatasi is the
      vector of Leishmania major, a causative agent of cutaneous leishmaniasis in the
      Old World, and its saliva exacerbates parasite proliferation and lesion growth in
      experimental cutaneous leishmaniasis. Here we show that P. papatasi saliva
      contains a potent inhibitor of protein phosphatase 1 and protein phosphatase 2A
      of murine macrophages. We further demonstrate that P. papatasi saliva down
      regulates expression of the inducible nitric oxide synthase gene and reduces
      nitric oxide production in murine macrophages. Partial biochemical
      characterization of the protein phosphatase and nitric oxide inhibitor indicated
      that it is a small, ethanol-soluble molecule resistant to boiling, proteolysis,
      and DNase and RNase treatments. We suggest that the P. papatasi salivary protein
      phosphatase inhibitor interferes with the ability of activated macrophages to
      transmit signals to the nucleus, thereby preventing up regulation of the induced
      nitric oxide synthase gene and inhibiting the production of nitric oxide. Since
      nitric oxide is toxic to intracellular parasites, the salivary protein
      phosphatase inhibitor may be the mechanism by which P. papatasi saliva
      exacerbates cutaneous leishmaniasis.

PMID- 9529079
TI  - Characterization of anticapsular monoclonal antibodies that regulate activation
      of the complement system by the Cryptococcus neoformans capsule.
AB  - Incubation of the encapsulated yeast Cryptococcus neoformans in human serum leads
      to alternative pathway-mediated deposition of C3 fragments in the capsule. We
      examined the ability of monoclonal antibodies (MAbs) specific for different
      epitopes of the major capsular polysaccharide to alter the kinetics for classical
      and alternative pathway-mediated deposition of C3 onto a serotype A strain. We
      studied MAbs reactive with capsular serotypes A, B, C, and D (MAb group II);
      serotypes A, B, and D (MAb group III); and serotypes A and D (MAb group IV). The
      MAb groupings are based on antibody variable region usage which determines the
      antibody molecular structure. When both the classical and alternative pathways
      were operative, group II MAbs induced early classical pathway-mediated binding of
      C3 but reduced the overall rate of C3 accumulation and the amount of bound C3.
      Group III MAbs closely mimicked the effects of group II MAbs but exhibited
      reduced support of early classical pathway-facilitated accumulation of C3.
      Depending on the antibody isotype, group IV MAbs slightly or markedly enhanced
      early binding of C3 but had no effect on either the rate of C3 accumulation or
      the amount of bound C3. When the classical pathway was blocked, group II and III
      MAbs markedly suppressed C3 binding that normally would have occurred via the
      alternative pathway. In contrast, MAbs of group IV had no effect on alternative
      pathway-mediated C3 binding. These results indicate that anticapsular antibodies
      with different epitope specificities may have distinct regulatory effects on
      activation and binding of C3.

PMID- 9529080
TI  - Bivalency is required for anticapsular monoclonal antibodies to optimally
      suppress activation of the alternative complement pathway by the Cryptococcus
      neoformans capsule.
AB  - Encapsulated cells of Cryptococcus neoformans are potent activators of the
      alternative complement pathway. Previous studies found that monoclonal antibodies
      (MAbs) specific for the major capsular polysaccharide, termed glucuronoxylomannan
      (GXM), can markedly suppress the ability of the capsule to accumulate C3 from
      normal human serum via the alternative pathway. The present study examined the
      abilities of F(ab)2 and Fab fragments of three MAbs (MAbs 439, 3C2, and 471) to
      mediate the suppressive effect. The results showed that F(ab)2 fragments of all
      three MAbs suppressed activation and binding of C3 via the alternative pathway in
      a manner similar to that of intact antibodies. In contrast, Fab fragments of MAb
      439 and MAb 3C2 showed no suppressive activity, and Fab fragments of MAb 471 were
      markedly reduced in suppressive activity. Indeed, there was an earlier
      accumulation of C3 on encapsulated cryptococci in the presence of the Fab
      fragments. Study of subclass switch families of MAb 439 and MAb 471 found that
      MAbs of an immunoglobulin G (IgG) subclass with increased flexibility in the
      hinge region (IgG2b) had less suppressive activity than MAbs of IgG subclasses
      with less flexibility (IgG1 or IgG2a). Taken together, these results indicate
      that cross-linking of the capsular matrix is an essential component in
      suppression of the alternative complement pathway by anti-GXM MAbs.

PMID- 9529081
TI  - Antigen-specific CD8+ T cells protect against lethal toxoplasmosis in mice
      infected with Neospora caninum.
AB  - Neospora caninum is a coccidial protozoan parasite that appears morphologically
      indistinguishable from Toxoplasma gondii and that infects a large range of
      mammals. Both inbred and outbred strains of mice exhibit a high degree of
      resistance to infection with N. caninum. Three inbred strains of mice (A/J,
      BALB/c, and C57BL/6) that were infected intraperitoneally with N. caninum were
      protected against a lethal challenge from T. gondii. Vaccine-induced protection
      was Neospora dose dependent. A rise in the CD8+ T-cell population in mice that
      had been vaccinated with N. caninum and challenged with T. gondii was observed.
      Adoptive transfer of CD8+ T-cell splenocytes from N. caninum-infected mice was
      protective against challenge with Toxoplasma. The CD8+ T cells from Neospora
      infected mice proliferate to both Neospora and Toxoplasma antigens in vitro and
      secrete substantial quantities of gamma interferon when pulsed with the parasite
      antigen. These observations demonstrate that N. caninum protects against lethal
      T. gondii infection by the induction of CD8+ T cells that are immunoreactive to
      both parasites.

PMID- 9529082
TI  - Helper T-cell epitopes encoded by the Babesia bigemina rap-1 gene family in the
      constant and variant domains are conserved among parasite strains.
AB  - Among important candidates for babesial vaccines are apical complex proteins,
      including rhoptry-associated protein 1 (RAP-1) from Babesia bovis and B.
      bigemina, which have been shown to induce partial immunity. Four variant B.
      bigemina rap-1 transcripts identified in a clone of the Mexico strain have highly
      conserved sequence in the central region but vary in sequence at the amino and
      carboxy termini (NT and CT) of the predicted proteins, resulting in different
      combinations of NT and CT domains in the individual gene products. Cattle were
      immunized with native protein consisting of the RAP-alpha1 variant, which
      contains NT-1 and CT-1 domains, and T-cell responses were characterized. We
      previously reported the identification of two T helper (Th) cell epitopes in B.
      bigemina RAP-1alpha1 protein (I. Hotzel, W. C. Brown, T. F. McElwain, S. D.
      Rodriguez, and G. H. Palmer, Mol. Biochem. Parasitol. 81:89-99, 1996). One
      epitope mapped to the constant domain of RAP-1 (amino acids [aa] 144 to 187), and
      one mapped to the CT-1 variable domain (aa 386 to 480). Th1-like clones
      responding to these epitopes proliferated differentially to different strains of
      B. bigemina, raising the possibilities that the T-cell epitopes may vary
      antigenically and that CT-1 may be differentially expressed with respect to the
      other RAP-1 CT domains in the different strains. In this report, we definitively
      map the T-cell epitope identified in the constant domain of RAP-1 to aa 159 to
      187 (FVVSLLKKNVVRDPESNDVENFASQYFYM) and show that the predicted amino acid
      sequence is completely conserved among seven strains. The T-cell epitope in the
      CT-1 domain was mapped to aa 436 to 465 (VNSEKVDADDAGNAETQQLPDAENEVRADD), which
      is also completely conserved among eight strains of B. bigemina. We further show
      that the RAP-1alpha1-immunized cattle were protected against homologous B.
      bigemina challenge, thus suggesting an association between protective immunity
      and the helper T-cell response against the two epitopes. The immunogenic and
      highly conserved nature of these T-cell epitopes and their ability to stimulate
      functionally relevant Th cells that express gamma interferon support their
      inclusion in a vaccine.

PMID- 9529083
TI  - Role of intimin and bundle-forming pili in enteropathogenic Escherichia coli
      adhesion to pediatric intestinal tissue in vitro.
AB  - Attaching and effacing (A/E) lesion formation is central to enteropathogenic
      Escherichia coli (EPEC) pathogenesis. In vitro experiments with human epithelial
      cell lines have implicated virulence plasmid-encoded bundle-forming pili (BFP) in
      initial binding and intimin in intimate attachment and A/E lesion formation. This
      study investigated the role of BFP and intimin in EPEC interactions with
      pediatric small intestinal biopsy tissue in in vitro organ culture. Organ culture
      infections (2 to 8 h) were performed with E2348/69 (a wild-type EPEC O127:H6
      clinical isolate) and E2348/69 derivatives including CVD206 (eae deficient),
      CVD206(pCVD438) (eae-complemented CVD206), CVD206(pCVD438/01) (expressing
      intimin, which is nonfunctional due to a single amino acid substitution), JPN15
      (spontaneous EPEC adherence factor virulence plasmid-cured E2348/69), and 31-6
      1(1) (E2348/69 with a TnphoA insertion inactivation mutation in the virulence
      plasmid-encoded bfpA gene). Scanning and transmission electron microscopy
      revealed that after 8 h E2348/69 and CVD206 (pCVD438) (both Int+ BFP+) adhered to
      all specimens, causing A/E lesions with surrounding microvillous elongation.
      JPN15 and 31-6-1(1) (both Int+ BFP-) adhered and caused A/E lesions although
      bacteria adhered in "flat," two-dimensional groups. CVD206 and CVD206(pCVD438/01)
      (both Int- BFP+) did not adhere to any sample, and no pathological tissue changes
      were seen. Thus, in human intestinal organ culture, BFP do not appear to be
      involved in the initial stages of EPEC nonintimate adhesion but are implicated in
      the formation of complex, three-dimensional colonies via bacterium-bacterium
      interactions. Intimin appears to play an essential role in establishing
      colonization of EPEC on pediatric small intestinal tissue.

PMID- 9529084
TI  - Characterization of leptospiral outer membrane lipoprotein LipL36: downregulation
      associated with late-log-phase growth and mammalian infection.
AB  - We report the cloning of the gene encoding a 36-kDa leptospiral outer membrane
      lipoprotein, designated LipL36. We obtained the N-terminal amino acid sequence of
      a staphylococcal V8 proteolytic-digest fragment in order to design an
      oligonucleotide probe. A Lambda-Zap II library containing EcoRI fragments of
      Leptospira kirschneri DNA was screened, and a 2.3-kb DNA fragment which contained
      the entire structural lipL36 gene was identified. Several lines of evidence
      indicate that LipL36 is lipid modified in a manner similar to that of LipL41, a
      leptospiral outer membrane lipoprotein we described in a previous study (E. S.
      Shang, T. A. Summers, and D. A. Haake, Infect. Immun. 64:2322-2330, 1996). The
      deduced amino acid sequence of LipL36 would constitute a 364-amino-acid
      polypeptide with a 20-amino-acid signal peptide, followed by an L-X-Y-C
      lipoprotein signal peptidase cleavage site. LipL36 is solubilized by Triton X-114
      extraction of L. kirschneri; phase separation results in partitioning of LipL36
      exclusively into the hydrophobic, detergent phase. LipL36 is intrinsically
      labeled during incubation of L. kirschneri in media containing [3H]palmitate.
      Processing of LipL36 is inhibited by globomycin, a selective inhibitor of
      lipoprotein signal peptidase. After processing, LipL36 is exported to the outer
      membrane along with LipL41 and lipopolysaccharide. Unlike LipL41, there appears
      to be differential expression of LipL36. In early-log-phase cultures, LipL36 is
      one of the most abundant L. kirschneri proteins. However, LipL36 levels drop
      considerably beginning in mid-log phase. LipL36 expression in vivo was evaluated
      by examining the humoral immune response to leptospiral antigens in the hamster
      model of leptospirosis. Hamsters surviving challenge with culture-adapted
      virulent L. kirschneri generate a strong antibody response to LipL36. In
      contrast, sera from hamsters surviving challenge with host-adapted L. kirschneri
      do not recognize LipL36. These findings suggest that LipL36 expression is
      downregulated during mammalian infection, providing a marker for studying the
      mechanisms by which pathogenic Leptospira species adapt to the host environment.

PMID- 9529085
TI  - Purification and characterization of a cytotoxic exolipid of Burkholderia
      pseudomallei.
AB  - Burkholderia pseudomallei is the causative agent of melioidosis, an infectious
      disease, which is increasingly recognized as an important public health problem
      in various tropical regions. This study describes the identification and
      characterization of a heat-stable extracellular toxin of B. pseudomallei. After
      cultivation of B. pseudomallei in liquid media, the heated cell-free supernatant
      was concentrated by ultrafiltration. The concentrate exhibited a cytotoxic and
      hemolytic activity which showed remarkable resistance against alkaline and acidic
      treatments. For further purification, reversed-phase chromatography using a fast
      performance liquid chromatography system was performed. After elution with an
      acetonitrile gradient, a single cytotoxic and hemolytic peak was detected.
      Structural characterization of the toxin was performed by a combination of mass
      spectrometric and nuclear magnetic resonance spectroscopic techniques. A highly
      purified glycolipid, 2-O-alpha-L-rhamnopyranosyl-alpha-L-rhamnopyranosyl-beta
      hydroxytetradec anoyl-beta-hydroxytetradecanoate (Rha-Rha-C14-C14), with a
      molecular mass of 762 Da was identified. The purified exolipid showed a time- and
      dose-dependent cytotoxic effect on phagocytic (HL60) and nonphagocytic (HeLa)
      cell lines. In addition, a time- and dose-dependent hemolysis of erythrocytes
      from various species was observed. The toxin structure makes a detergentlike
      action most probable. Interestingly, the cytotoxic and hemolytic activities of
      the glycolipid could be neutralized by albumin. Future studies will concentrate
      on the role of this exolipid as a virulence factor in the pathogenesis of
      melioidosis.

PMID- 9529086
TI  - Maturation of the arginine-specific proteases of Porphyromonas gingivalis W50 is
      dependent on a functional prR2 protease gene.
AB  - The prpR1 of Porphyromonas gingivalis codes for three distinct enzymes with
      specificity for arginyl peptide bonds termed RI, RIA, and RIB. These three
      isoforms comprise the majority of the extracellular, arginine-specific protease
      activity in P. gingivalis W50. RI is a heterodimer in which the catalytic alpha
      chain is noncovalently associated with a second chain involved in adherence
      phenomena. RIA and RIB are both monomeric species. RIA represents the free alpha
      chain, and RIB is a highly posttranslationally modified form of the alpha chain
      which is exclusively vesicle or membrane associated and migrates as a diffuse
      band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. In previous
      studies, insertional inactivation of the prpR1 demonstrated that arginine
      specific protease activity can also arise from a closely related second gene,
      prR2. In the present work, the prR2 was insertionally inactivated in P.
      gingivalis W50 in order to establish the contribution of this locus to the
      arginine-specific protease activity of this periodontal bacterium. Loss of prR2
      function had several effects on prpR1-derived enzymes. First, the total Arg-X
      activity was reduced by approximately 50% relative to that of the parent strain.
      The reduction in total activity was a consequence of decreased concentrations of
      the monomeric enzymes derived from the prpR1, while the heterodimeric enzyme, RI,
      was unaffected by this mutation. Second, the chromatographic behavior of both the
      soluble and vesicle- or membrane-associated monomeric enzymes was radically
      different from the behavior of RIA and RIB from the parent strain. Finally, the
      vesicle- or membrane-associated enzyme in the prR2 mutant strain lacked the
      extensive posttranslational additions which are found on RIB in P. gingivalis
      W50. These data suggest that the product(s) of the prR2 plays a significant role
      in the maturation pathway of prpR1-derived enzymes, and this may contribute to
      the coconservation of these two genes in P. gingivalis.

PMID- 9529087
TI  - Phagocytosis of the malarial pigment, hemozoin, impairs expression of major
      histocompatibility complex class II antigen, CD54, and CD11c in human monocytes.
AB  - In Plasmodium falciparum malaria, large proportions of resident macrophages and
      circulating monocytes and leukocytes contain massive amounts of the malarial
      pigment, hemozoin. Previous studies have shown that important functions (e.g.,
      the generation of the oxidative burst, the ability to repeat phagocytosis, and
      protein kinase C activity) were severely impaired in hemozoin-loaded monocytes.
      Expression of membrane antigens directly involved in the immune response and in
      the phagocytic process, and/or under protein kinase C control, in hemozoin-loaded
      human monocytes was studied. Expression of major histocompatibility complex (MHC)
      class II after gamma interferon stimulation was blocked in hemozoin-loaded
      monocytes at the protein expression and gene transcription levels but was
      preserved in control monocytes loaded with opsonized latex beads or anti-D(Rho)
      immunoglobulin G (IgG)-opsonized human erythrocytes. Expression of CD54
      (intracellular adhesion molecule 1) and CD11c (p150,95 integrin) was also
      decreased in hemozoin-loaded monocytes. Expression of MHC class I, CD16 (low
      affinity Fc receptor for aggregated IgG), CD32 (low-affinity Fc receptor for
      aggregated IgG), CD64 (high-affinity receptor for IgG), CD11b (receptor for
      complement component iC3b [CR3]), CD35 (receptor for complement components C3b
      and C4b [CR1]), and CD36 (non-class-A scavenger receptor) was not specifically
      affected by hemozoin loading. These results suggest that hemozoin loading may
      contribute to the impairment of the immune response and the derangement of
      antigen presentation reported in previous studies of P. falciparum malaria.

PMID- 9529088
TI  - Human mannose-binding protein inhibits infection of HeLa cells by Chlamydia
      trachomatis.
AB  - The role that collectin (mannose-binding protein) may play in the host's defense
      against chlamydial infection was investigated. Recombinant human mannose-binding
      protein was used in the inhibition of cell culture infection by Chlamydia
      trachomatis (C/TW-3/OT, E/UW-5/Cx, and L2/434/Bu), Chlamydia pneumoniae (AR-39),
      and Chlamydia psittaci (6BC). Mannose-binding protein (MBP) inhibited infection
      of all chlamydial strains by at least 50% at 0.098 microg/ml for TW-3 and UW-5,
      and at 6.25 microg/ml for 434, AR-39, and 6BC. The ability of MBP to inhibit
      infection with strain L2 was not affected by supplementation with complement or
      addition of an L2-specific neutralizing monoclonal antibody. Enzyme-linked
      immunosorbent assay and dot blot analyses showed MBP bound to the surface of the
      organism to exert inhibition, which appeared to block the attachment of
      radiolabeled organisms to HeLa cells. Immunoblotting and affinity chromatography
      indicated that MBP binds to the 40-kDa glycoprotein (the major outer membrane
      protein) on the outer surface of the chlamydial elementary body. Hapten
      inhibition assays with monosaccharides and defined oligosaccharides showed that
      the inhibitory effects of MBP were abrogated by mannose or high-mannose type
      oligomannose-oligosaccharide. The latter carbohydrate is the ligand of the 40-kDa
      glycoprotein of C. trachomatis L2, which is known to mediate attachment,
      suggesting that the MBP binds to high mannose moieties on the surface of
      chlamydial organisms. These results suggest that MBP plays a role in first-line
      host defense against chlamydial infection in humans.

PMID- 9529089
TI  - Characterization of the carbohydrate moiety of intestinal mucin-type
      sialoglycoprotein receptors for the K88ac fimbrial adhesin of Escherichia coli.
AB  - We have previously identified two mucin-type sialoglycoproteins from porcine
      intestinal epithelial cells with approximate molecular masses of 210 (intestinal
      mucin-type glycoprotein IMTGP-1) and 240 kDa (IMTGP-2) as receptors for the K88ab
      and K88ac fimbrial adhesins of Escherichia coli. These receptors are detected in
      intestinal brush border membrane preparations from pigs with adhesive phenotypes
      but not from pigs with nonadhesive phenotypes and are postulated to be important
      determinants of the susceptibility of pigs to K88ab+ and K88ac+ enterotoxigenic
      E. coli infections. Using exoglycosidase digestion studies, we have now
      determined that beta-linked galactose is an important component in the
      recognition of IMTGP-1 and IMTGP-2 by the K88ac adhesin. In addition, we observed
      a differential distribution of the K88ac adhesin binding activity of IMTGP-1 and
      IMTGP-2 along the crypt-villus axis, suggesting that receptor activity is
      dependent on the maturation state of the intestinal epithelial cells. Brush
      borders from immature intestinal epithelial cells possessed the highest
      concentrations of IMTGP-1 and IMTGP-2 receptor activity, with a progressive
      decrease in receptor activity as the cells mature. To characterize the
      differences in the carbohydrate moieties of IMTGP-1 and IMTGP-2, we developed a
      procedure for purifying the receptors, using phenol extraction followed by serial
      lectin affinity chromatography. Carbohydrate compositional analysis of the
      purified receptors indicated that the carbohydrate moieties of IMTGP-1 and IMTGP
      2 consist of both N- and O-glycans containing galactose, glucose, sialic acid,
      mannose, N-acetylgalactosamine, N-acetylglucosamine, and fucose. The major
      difference between the two receptors is that IMTGP-2 contains a higher percentage
      of monosaccharides (mannose and glucose) commonly found in N-glycans.

PMID- 9529090
TI  - Copy number of pilus gene clusters in Haemophilus influenzae and variation in the
      hifE pilin gene.
AB  - Brazilian purpuric fever (BPF)-associated Haemophilus influenzae biogroup
      aegyptius strain F3031 contains two identical copies of a five gene cluster (hifA
      to hifE) encoding pili similar to well-characterized Hif fimbriae of H.
      influenzae type b. HifE, the putative pilus tip adhesin of F3031, shares only 40%
      amino acid sequence similarity with the same molecule from type b strains,
      whereas the other four proteins have 75 to 95% identity. To determine whether
      pilus cluster duplication and the hifE(F3031) allele were special features of BPF
      associated bacteria, we analyzed a collection of H. influenzae strains by PCR
      with hifA- and hifE-specific oligonucleotides, by Southern hybridization with a
      hifC gene probe, and by nucleotide sequencing. The presence of two pilus clusters
      was limited to some H. influenzae biogroup aegyptius strains. The hifE(F3031)
      allele was limited to H. influenzae biogroup aegyptius. Two strains contained one
      copy of hifE(F3031) and one copy of a variant hifE allele. We determined the
      nucleotide sequences of four hifE genes from H. influenzae biogroup aegyptius and
      H. influenzae capsule serotypes a and c. The predicted proteins produced by these
      genes demonstrated only 35 to 70% identity to the three published HifE proteins
      from nontypeable H. influenzae, serotype b, and BPF strains. The C-terminal third
      of the molecules implicated in chaperone binding was the most highly conserved
      region. Three conserved domains in the otherwise highly variable N-terminal
      putative receptor-binding region of HifE were similar to conserved portions in
      the N terminus of Neisseria pilus adhesin PilC. We concluded that two pilus
      clusters and hifE(F3031) were not specific for BPF-causing H. influenzae, and we
      also identified portions of HifE possibly involved in binding mammalian cell
      receptors.

PMID- 9529091
TI  - Expressed sequence tag analysis of the bradyzoite stage of Toxoplasma gondii:
      identification of developmentally regulated genes.
AB  - Toxoplasma gondii is a protozoan parasite responsible for widespread infections
      in humans and animals. Two major asexual forms are produced during the life cycle
      of this parasite: the rapidly dividing tachyzoite and the more slowly dividing,
      encysted bradyzoite. To further study the differentiation between these two
      forms, we have generated a large number of expressed sequence tags (ESTs) from
      both asexual stages. Previously, we obtained data on approximately 7,400 ESTs
      from tachyzoites (J. Ajioka et al., Genome Res. 8:18-28, 1998). Here, we report
      the results from analysis of approximately 2,500 ESTs from bradyzoites purified
      from the cysts of infected mice. We also report the results from analysis of 760
      ESTs from parasites induced to differentiate from tachyzoites to bradyzoites in
      vitro. Comparison of the data sets from bradyzoites and tachyzoites reveals many
      previously uncharacterized sequence clusters which are largely or completely
      specific to one or other developmental stage. This class includes a bradyzoite
      specific form of enolase. Combined with the previously identified bradyzoite
      specific form of lactate dehydrogenase, this finding suggests significant
      differences in flux through the lower end of the glycolytic pathway in this
      stage. Thus, the generation of this data set provides valuable insights into the
      metabolism and growth of the parasite in the encysted form and represents a
      substantial body of information for further study of development in Toxoplasma.

PMID- 9529092
TI  - Nuclear translocation of NF-kappaB in lipopolysaccharide-treated macrophages
      fails to correspond to endotoxicity: evidence suggesting a requirement for a
      gamma interferon-like signal.
AB  - Elucidation of a signal transduction pathway essential to lipopolysaccharide
      (LPS)-induced macrophage activation has the capacity to provide new targets for
      the treatment of septic shock. In this regard, activation of the transcription
      factor NF-kappaB is commonly thought to be critical to LPS-stimulated macrophage
      inflammatory mediator production, although certain immunological, genetic, and
      molecular evidence suggests that other factors are involved. To address this
      issue, we hypothesized that the degree of LPS-induced NF-kappaB mobilization
      should correlate with the murine endotoxicity of the species of LPS used for in
      vitro study. Therefore, using D-galactosamine-sensitized mice, we assessed the
      lethal potencies of eight LPS preparations from Escherichia, Salmonella,
      Klebsiella, Bacteroides, Pseudomonas, Neisseria, and Rhodobacter species as well
      as that of the endotoxin substructure lipid X. The lethal potencies of these LPS
      preparations varied by > 160-fold. Treatment of RAW 264.7 cells with the same LPS
      preparations induced levels of tumor necrosis factor alpha (TNF-alpha) and NO
      production that correlated with the LPS 50% lethal dose. The combined analysis of
      the levels of these two mediators produced in response to LPS in RAW cells was
      found to be a strong predictor of murine endotoxic lethality. Interestingly,
      while relatively nontoxic in mice, Rhodobacter capsulatus LPS stimulated RAW cell
      NF-kappaB-like DNA binding protein mobilization and TNF-alpha production to
      levels comparable to those of more toxic species of LPS but was unable to induce
      NO generation in RAW cells. These data indicate that neither NF-kappaB activation
      nor TNF-alpha production alone is a dependable predictor of LPS lethality.
      Additionally, cotreatment of RAW cells with the potent inflammatory mediator ADP
      had no effect on the ability of R. capsulatus LPS to stimulate NO production but
      significantly enhanced induction of NO production by the toxic species of LPS. In
      contrast, cotreatment of RAW cells or peritoneal macrophages with gamma
      interferon (IFN-gamma) normalized the abilities of both toxic and nontoxic LPS
      preparations to induce NO production, suggesting that selected preparations of
      LPS may preferentially generate an IFN-gamma-like signal that accounts for
      enhanced toxicity. In sum, the activation of NF-kappaB does not correspond to LPS
      lethality, thereby complicating models of macrophage activation that highlight NF
      kappaB alone as a signal transduction factor necessary for LPS-mediated toxicity.

PMID- 9529093
TI  - A recombinant live attenuated strain of Vibrio cholerae induces immunity against
      tetanus toxin and Bordetella pertussis tracheal colonization factor.
AB  - An attenuated strain of Vibrio cholerae was used as a carrier for the expression
      of heterologous antigens such as fragment C from tetanus toxin (TetC) and
      tracheal colonization factor from Bordetella pertussis (Tcf). In vitro, high
      levels of protein were obtained when the Escherichia coli nirB promoter was used
      and the bacteria were grown with low aeration. Intranasal immunization of mice
      with IEM101 expressing TetC elicited serum vibriocidal activity and induced
      antibodies against tetanus toxin which were protective against lethal challenge
      with 10 times the 50% lethal dose of tetanus toxin. Bacterial viability was
      essential for the induction of anti-TetC antibodies. Intranasal administration of
      IEM101 expressing Tcf induced a significant reduction in bacterial colonization
      of the tracheas of mice challenged with wild-type B. pertussis. These data are in
      agreement with the putative role of Tcf in Bordetella tracheal colonization. In
      conclusion, we have demonstrated that V. cholerae may be used as a live vector to
      deliver heterologous antigens in vivo and that protection to both systemic and
      local challenge may be achieved.

PMID- 9529094
TI  - Decreased antitoxic activities among children with clinical episodes of malaria.
AB  - Healthy Gambian children, children with clinical Plasmodium falciparum malaria,
      and children with asymptomatic P. falciparum infections were studied to
      investigate whether antitoxic activities may contribute to protection against
      malarial symptoms. Markers of inflammatory reactions, soluble tumor necrosis
      factor receptor I, and C-reactive protein were found in high concentrations in
      children with symptomatic P. falciparum malaria compared with levels in children
      with asymptomatic P. falciparum infections or in healthy children, indicating
      that inflammatory reactions are induced only in children with clinical symptoms.
      Concentrations of soluble tumor necrosis factor receptor I and C-reactive protein
      were associated with levels of parasitemia. We detected antitoxic activities in
      sera as measured by their capacity to block toxin-induced Limulus amoebocyte
      lysate (LAL) activation. Symptomatic children had decreased capacity to block
      induction of LAL activation by P. falciparum exoantigen. The decreased blocking
      activity was restored in the following dry season, when the children had no
      clinical malaria. Symptomatic children also had the highest immunoglobulin G
      (IgG) reactivities to conserved P. falciparum erythrocyte membrane protein 1 and
      "Pfalhesin" (band #3) peptides, indicating that such IgG antibodies are
      stimulated by acute disease but are lost rapidly after the disease episode. Half
      of the children with symptomatic infections had low levels of haptoglobin,
      suggesting that these children had chronic P. falciparum infections which may
      have caused symptoms previously. Only a few of the children with asymptomatic P.
      falciparum infections had high parasite counts, and antitoxic immunity in the
      absence of antiparasite immunity appears to be rare among children in this
      community.

PMID- 9529095
TI  - Local chemokine paralysis, a novel pathogenic mechanism for Porphyromonas
      gingivalis.
AB  - Periodontitis, which is widespread in the adult population, is a persistent
      bacterial infection associated with Porphyromonas gingivalis. Gingival epithelial
      cells are among the first cells encountered by both P. gingivalis and commensal
      oral bacteria. The chemokine interleukin 8 (IL-8), a potent chemoattractant and
      activator of polymorphonuclear leukocytes, was secreted by gingival epithelial
      cells in response to components of the normal oral flora. In contrast, P.
      gingivalis was found to strongly inhibit IL-8 accumulation from gingival
      epithelial cells. Inhibition was associated with a decrease in mRNA for IL-8.
      Antagonism of IL-8 accumulation did not occur in KB cells, an epithelial cell
      line that does not support high levels of intracellular invasion by P.
      gingivalis. Furthermore, a noninvasive mutant of P. gingivalis was unable to
      antagonize IL-8 accumulation. Invasion-dependent destruction of the gingival IL-8
      chemokine gradient at sites of P. gingivalis colonization (local chemokine
      paralysis) will severely impair mucosal defense and represents a novel mechanism
      for bacterial colonization of host tissue.

PMID- 9529096
TI  - Adequate expression of protective immunity in the absence of granuloma formation
      in Mycobacterium tuberculosis-infected mice with a disruption in the
      intracellular adhesion molecule 1 gene.
AB  - It remains unknown whether the expression of cell-mediated protective immunity
      and the capacity to mount a delayed-type hypersensitivity (DTH) reaction in
      tuberculosis infection represent two manifestations of a basic response or are
      dissociable events. In this study, we present data in favor of the latter
      hypothesis, by showing that tuberculosis infection in the lungs of mice
      possessing only a truncated form of intracellular adhesion molecule 1 due to gene
      disruption was still adequately controlled by the expression of protective
      immunity in the absence of any sustained influx of macrophages and the lack of
      formation of appreciable granulomas. These animals also had no detectable DTH
      response to mycobacterial proteins in the footpad assay, indicating that the
      accumulation of blood-borne macrophages at sites of mycobacterial infection or
      antigen deposition is not essential to control of the infection. These data
      support the hypothesis that the DTH component of the cellular response is not
      protective but contributes by walling off the sites of infection to prevent
      dissemination and reactivation disease.

PMID- 9529097
TI  - Reduced virulence of group A streptococcal Tn916 mutants that do not produce
      streptolysin S.
AB  - Streptolysin S (SLS) is a potent cytolytic toxin produced by nearly all group A
      streptococci (GAS). SLS-deficient Tn916 insertional mutants were generated from
      two clinical isolates of GAS, MGAS166s and T18Ps (M serotypes 1 and 18,
      respectively), by transposon mutagenesis using Tn916 donor strain Enterococcus
      faecalis CG110. Representative nonhemolytic transconjugants SBNH5 and SB30-2 each
      harbored a single Tn916 insertion in identical loci. The insertion in SBNH5 was
      located in the promoter region of an open reading frame, designated sagA,
      rendering it transcriptionally inactive. Protease, streptolysin O, and DNase
      activities and the production of M protein remained the same in the nonhemolytic
      mutants and the wild-type strains, as did the growth rates and exoprotein
      profiles. Transconjugants were evaluated in an established murine model by
      injecting the organisms subcutaneously and monitoring the mice for alterations in
      weight and the development of necrotic lesions. Animals infected with SBNH5,
      compared to those infected with MGAS166s, gained weight during the first 24 h
      (+1.15 versus -1.16 g; P < 0.05) and had fewer necrotic lesions (0 versus 7; P =
      0.0007). Animals infected with SB30-2, compared to those infected with T18Ps,
      also gained weight within the first 24 h (+0.54 versus -0.66 g; P < 0.05) and
      produced fewer necrotic lesions (1 versus 8; P = 0.001). Revertants of the
      mutants in which Tn916 had been excised regained the hemolytic phenotype and the
      virulence profile of the wild-type strains. This study demonstrates that SLS
      deficient mutants of GAS, belonging to different M serotypes and containing
      identical Tn916 mutations, are markedly less virulent than their isogenic
      parents.

PMID- 9529098
TI  - Signal transduction pathways involved in enterohemorrhagic Escherichia coli
      induced alterations in T84 epithelial permeability.
AB  - Enterohemorrhagic Escherichia coli (EHEC) infection is associated with watery
      diarrhea and can lead to complications, including hemorrhagic colitis and the
      hemolytic-uremic syndrome. The mechanisms by which these organisms produce
      diarrheal disease remain to be elucidated. Changes in T84 epithelial cell
      electrophysiology were examined following EHEC infection. T84 cell monolayers
      infected with EHEC O157:H7 displayed a time-dependent decrease in transepithelial
      resistance. Increases in the transepithelial flux of both [3H]mannitol and 51Cr
      EDTA accompanied the EHEC-induced decreases in T84 resistance. Altered barrier
      function induced by EHEC occurred at the level of the tight junction since
      immunofluorescent staining of the tight-junction-associated protein ZO-1 was
      disrupted when examined by confocal microscopy. Decreased resistance induced by
      EHEC involved a protein kinase C (PKC)-dependent pathway as the highly specific
      PKC inhibitor, CGP41251, abrogated the EHEC-induced drop in resistance. PKC
      activity was also increased in T84 cells infected with EHEC. Calmodulin and
      myosin light chain kinase played a role in EHEC-induced resistance changes as
      inhibition of these effector molecules partially reversed the effects of EHEC on
      barrier function. These studies demonstrate that intracellular signal
      transduction pathways activated following EHEC infection link the increases in
      T84 epithelial permeability induced by this pathogen.

PMID- 9529099
TI  - Divergent signal transduction responses to infection with attaching and effacing
      Escherichia coli.
AB  - Shiga toxin-producing Escherichia coli (STEC) O157:H7 is an attaching and
      effacing pathogen that causes hemorrhagic colitis and the hemolytic-uremic
      syndrome. Although this organism causes adhesion pedestals, the cellular signals
      responsible for the formation of these lesions have not been clearly defined. We
      have shown previously that STEC O157:H7 does not induce detectable tyrosine
      phosphorylation of host cell proteins upon binding to eukaryotic cells and is not
      internalized into nonphagocytic epithelial cells. In the present study, tyrosine
      phosphorylated proteins were detected under adherent STEC O157:H7 when
      coincubated with the non-intimately adhering, intimin-deficient, enteropathogenic
      E. coli (EPEC) strain CVD206. The ability to be internalized into epithelial
      cells was also conferred on STEC O157:H7 when coincubated with CVD206 ([158 +/-
      21] % of control). Neither the ability to rearrange phosphotyrosine proteins nor
      that to be internalized into epithelial cells was evident following coincubation
      with another STEC O157:H7 strain or with the nonsignaling espB mutant of EPEC. E.
      coli JM101(pMH34/pSSS1C), which overproduces surface-localized O157 intimin, also
      rearranged tyrosine-phosphorylated and cytoskeletal proteins when coincubated
      with CVD206. In contrast, JM101 (pMH34/pSSS1C) demonstrated rearrangement of
      cytoskeletal proteins, but not tyrosine-phosphorylated proteins, when coincubated
      with intimin-deficient STEC (strains CL8KO1 and CL15). These findings indicate
      that STEC O157:H7 forms adhesion pedestals by mechanisms that are distinct from
      those in attaching and effacing EPEC. Taken together, these findings point to
      diverging signal transduction responses to infection with attaching and effacing
      bacterial enteropathogens.

PMID- 9529100
TI  - Electrotransformation and expression of bacterial genes encoding hygromycin
      phosphotransferase and beta-galactosidase in the pathogenic fungus Histoplasma
      capsulatum.
AB  - We developed an efficient electrotransformation system for the pathogenic fungus
      Histoplasma capsulatum and used it to examine the effects of features of the
      transforming DNA on transformation efficiency and fate of the transforming DNA
      and to demonstrate fungal expression of two recombinant Escherichia coli genes,
      hph and lacZ. Linearized DNA and plasmids containing Histoplasma telomeric
      sequences showed the greatest transformation efficiencies, while the plasmid
      vector had no significant effect, nor did the derivation of the selectable URA5
      marker (native Histoplasma gene or a heterologous Podospora anserina gene).
      Electrotransformation resulted in more frequent multimerization, other
      modification, or possibly chromosomal integration of transforming telomeric
      plasmids when saturating amounts of DNA were used, but this effect was not
      observed with smaller amounts of transforming DNA. We developed another selection
      system using a hygromycin B resistance marker from plasmid pAN7-1, consisting of
      the E. coli hph gene flanked by Aspergillus nidulans promoter and terminator
      sequences. Much of the heterologous fungal sequences could be removed without
      compromising function in H. capsulatum, allowing construction of a substantially
      smaller effective marker fragment. Transformation efficiency increased when
      nonselective conditions were maintained for a time after electrotransformation
      before selection with the protein synthesis inhibitor hygromycin B was imposed.
      Finally, we constructed a readily detectable and quantifiable reporter gene by
      fusing Histoplasma URA5 with E. coli lacZ, resulting in expression of functional
      beta-galactosidase in H. capsulatum. Demonstration of expression of bacterial
      genes as effective selectable markers and reporters, together with a highly
      efficient electrotransformation system, provide valuable approaches for molecular
      genetic analysis and manipulation of H. capsulatum, which have proven useful for
      examination of targeted gene disruption, regulated gene expression, and potential
      virulence determinants in this fungus.

PMID- 9529101
TI  - Characteristics of invasive candidiasis in gamma interferon- and interleukin-4
      deficient mice: role of macrophages in host defense against Candida albicans.
AB  - Murine models of invasive candidiasis were used to study the in vivo importance
      of gamma interferon (IFN-gamma) and interleukin-4 (IL-4) in host defense against
      Candida albicans and to characterize the tissue inflammatory reactions, with
      special reference to macrophages (Mphi). Knockout (KO) IFN-gamma-deficient (GKO)
      and IL-4-deficient (IL-4 KO) and C57BL/6 parental mouse strains were challenged
      intraperitoneally with 10(8) C. albicans blastoconidia. Survival of GKO mice was
      significantly lower (16.7%) than that of C57BL/6 control (55.5%) and IL-4 KO
      (61.1%) animals, but was not correlated with the extent of organ colonization.
      Immunohistological analysis with a panel of myeloid and lymphoid markers revealed
      multiple renal abscesses, myocarditis, hepatitis, meningoencephalitis, and
      pneumonia in each strain, with a dominant presence of Mphi. In the absence of IFN
      gamma, C. albicans induced striking changes in the phenotype of alveolar Mphi and
      extensive perivascular lymphoid infiltrates in the lung. Impairment in nitric
      oxide production by peritoneal Mphi was shown only in GKO mice, and they produced
      Candida-specific immunoglobulin G (IgG), IgM, IgA, and IgG subclasses in lower
      titers. Our in vivo studies with KO mice elucidate a critical role for IFN-gamma,
      but not IL-4, in host defense against C. albicans.

PMID- 9529102
TI  - Role of adenylate cyclase-hemolysin in alveolar macrophage apoptosis during
      Bordetella pertussis infection in vivo.
AB  - Bordetella pertussis induces in vitro apoptosis of murine alveolar macrophages by
      a mechanism that is dependent on expression of bacterial adenylate cyclase
      hemolysin. Using a murine respiratory model, we found in this study that
      intranasal infection with a parental B. pertussis strain, but not with an
      isogenic variant deficient in the expression of all toxins and adhesins, induced
      a marked neutrophil accumulation in the bronchoalveolar lavage fluid and an early
      decrease in macrophage numbers. These phenomena paralleled a time-dependent rise
      in the proportion of apoptotic nuclei, as detected by flow cytometry, and of
      macrophages which had engulfed apoptotic bodies. Apoptotic death of
      bronchopulmonary cells was observed exclusively following intranasal infection
      with bacteria reisolated from lungs of infected animals and not with B. pertussis
      collected after in vitro subculture. Using the terminal
      deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling technique
      coupled to fluorescence microscopy and morphological analysis, we established
      that the apoptotic cells in bronchoalveolar lavage fluids were neutrophils and
      macrophages. Histological analysis of the lung tissues from B. pertussis-infected
      mice showed increased numbers of apoptotic cells in the alveolar compartments.
      Cellular accumulation in bronchoalveolar lavage fluids and apoptosis of alveolar
      macrophages were significantly attenuated in mice infected with a mutant
      deficient in the expression of adenylate cyclase-hemolysin, indicating a role of
      this enzyme in these processes.

PMID- 9529103
TI  - Enhancement of susceptibility to Shiga toxin-producing Escherichia coli O157:H7
      by protein calorie malnutrition in mice.
AB  - Infection with Shiga toxin (Stx)-producing enterohemorrhagic Escherichia coli is
      increasing among children. In this study, 5-week-old C57BL/6 mice with protein
      calorie malnutrition (PCM) that had been fed a 5% protein diet for 2 weeks since
      ablactation were inoculated intragastrically with 2 x 106 CFU of Stx-producing E.
      coli O157:H7. More than 75% of infected mice with PCM died by 10 days
      postinfection. Infected mice with PCM developed neurologic symptoms 5 days after
      infection, while well-nourished control mice receiving a 25% protein diet did
      not. In the intestinal tracts of infected mice with PCM, inoculated E. coli
      O157:H7 multiplied between days 2 and 4 of infection, with a peak of growth at
      day 4. Although the pathogens were not culturable from the stool after day 7,
      0157 lipopolysaccharide was detectable in the stool by enzyme-linked
      immunosorbent assay even after day 8. Stx was detectable in the stool after day 2
      of infection and increased in proportion to the growth of inoculated organisms.
      The maximal production of Stx occurred at 4 days postchallenge, and Stx was
      detectable in the blood on days 3 to 5. In contrast, well-nourished control mice
      survived the infection, and all of them remained well even after 3 weeks of
      infection. In these control mice, inoculated E. coli O157:H7 disappeared from the
      stool before day 3. Stx was not detectable in the stool and blood of infected
      control mice at any time from day 1 through day 8. Histologically, cerebral
      hemorrhages seemed to be the cause of acute death of infected mice with PCM.
      Immunocytochemical staining demonstrated the positive immunoreaction to Stx at
      the alveus and stratum pyramidale of the hippocampus and in renal tubules of
      infected malnourished mice. Such immunoreactions were not found in tissues from
      infected control mice. Histological study of the intestinal epithelium before
      infection showed that PCM severely affected the development of intestinal
      epithelia. These findings strongly indicate that PCM-induced nondevelopment of
      intestinal physical barrier is one of the predisposing factors for infection with
      Stx-producing E. coli O157:H7 in mice and suggest that our mouse model may
      explain the high incidence of infection with Stx-producing E. coli O157:H7 in the
      children whose intestinal epithelia have not yet completely developed.

PMID- 9529104
TI  - Molecular characterization of the fragilysin pathogenicity islet of
      enterotoxigenic Bacteroides fragilis.
AB  - Enterotoxigenic strains of Bacteroides fragilis produce an extracellular
      metalloprotease toxin (termed fragilysin) which is cytopathic to intestinal
      epithelial cells and induces fluid secretion and tissue damage in ligated
      intestinal loops. We report here that the fragilysin gene is contained within a
      small genetic element termed the fragilysin pathogenicity islet. The
      pathogenicity islet of B. fragilis VPI 13784 was defined as 6,033 bp in length
      and contained nearly perfect 12-bp direct repeats near its ends. Sequencing
      across the ends of the pathogenicity islet from two additional enterotoxigenic
      strains, along with PCR analysis of 20 additional enterotoxigenic strains,
      revealed that the islet is inserted at a specific site on the B. fragilis
      chromosome. The site of integration in three nontoxigenic strains contained a 17
      bp GC-rich sequence which was not present in toxigenic strains and may represent
      a target sequence for chromosomal integration. In addition to the fragilysin
      gene, we identified an open reading frame encoding a predicted protein with a
      size and structural features similar to those of fragilysin. The deduced amino
      acid sequence was 28.5% identical and 56.3% similar to fragilysin and contained a
      nearly identical zinc-binding motif and methionine-turn region.

PMID- 9529105
TI  - Comparison of an adherence domain and a structural region of Streptococcus mutans
      antigen I/II in protective immunity against dental caries in rats after
      intranasal immunization.
AB  - Previous studies have identified an N-terminal saliva-binding region (SBR) on
      Streptococcus mutans surface antigen I/II (AgI/II) and suggested its importance
      in the initial adherence of S. mutans to saliva-coated tooth surfaces and
      subsequent development of dental caries. In this study, we compared the SBR with
      a C-terminal structural region of AgI/II (AgII) in their abilities to induce
      protective immunity against caries in rats. When SBR, AgII, or the whole AgI/II
      molecule was administered intranasally as a conjugate with the B subunit of
      cholera toxin (CT), in the presence of CT adjuvant, substantial levels of
      salivary immunoglobulin A anti-AgI/II antibodies were induced. Evaluation of
      caries activity showed that the SBR, though not as protective as the parent
      molecule, was superior to AgII and thus can be further considered as a component
      in a multivalent caries vaccine.

PMID- 9529106
TI  - Enhancement of lipopolysaccharide-induced neutrophil oxygen radical production by
      tumor necrosis factor alpha.
AB  - Although tissues become exposed to both exogenous and endogenous cell-activating
      mediators during infection, there is little appreciation of the effects of
      subjecting cells to multiple mediators. We examined the hypothesis that the
      response of neutrophils to bacterial lipopolysaccharide (LPS) is significantly
      altered in the presence of the endogenous mediator tumor necrosis factor alpha
      (TNF). The data showed that human neutrophils pretreated with TNF for 10 to 30
      min, displayed significantly enhanced superoxide production in response to LPS
      (from either Escherichia coli K-235 or E. coli O127:B8), measured as lucigenin
      dependent chemiluminescence (CL), seen as an increase in the initial peak rate as
      well as the total CL accumulated over the incubation period. TNF amplified the
      response to LPS at 1 to 100 U of TNF/10(6) neutrophils and was able to enhance
      the response to a wide range of concentrations of LPS (0.01 to 1,000 ng/ml). The
      TNF-induced increase in the LPS response was paralleled by an increase in LPS
      binding to the neutrophils, which could be abrogated by an anti-CD14 monoclonal
      antibody. The results demonstrate that TNF significantly increases the LPS
      induced release of oxygen radicals in neutrophils through the upregulation of
      cell surface CD14.

PMID- 9529107
TI  - Adherence to and penetration of human intestinal Caco-2 epithelial cell
      monolayers by Pseudomonas aeruginosa.
AB  - Clinical isolates of Pseudomonas aeruginosa from blood adhered to and penetrated
      intestinal Caco-2 cell monolayers to a greater degree than did isolates from
      sputum, with a concomitant drastic decrease in transepithelial electrical
      resistance. PAO-PR1, an avirulent exotoxin A mutant of PAO1, did not cause a
      decrease in the resistance. The Caco-2 monolayer system may be useful for the
      evaluation of certain P. aeruginosa virulence factor activities.

PMID- 9529108
TI  - Aging and the immune response to the Haemophilus influenzae type b capsular
      polysaccharide: retention of the dominant idiotype and antibody function in the
      elderly.
AB  - Anti-Haemophilus influenzae b polysaccharide (Hib PS) antibodies elicited in
      elderly subjects following conjugate vaccination expressed a light-chain variable
      region (VL)-associated idiotype and had functional activities similar to those
      previously observed in children and younger adults. These findings indicate that
      advanced age is not accompanied by shifts in the major VL component of the Hib PS
      specific repertoire or by diminution of the protective function of antibodies.

PMID- 9529109
TI  - Agents that inhibit Rho, Rac, and Cdc42 do not block formation of actin pedestals
      in HeLa cells infected with enteropathogenic Escherichia coli.
AB  - Enteropathogenic Escherichia coli (EPEC) induces formation of actin pedestals in
      infected host cells. Agents that inhibit the activity of Rho, Rac, and Cdc42,
      including Clostridium difficile toxin B (ToxB), compactin, and dominant negative
      Rho, Rac, and Cdc42, did not inhibit formation of actin pedestals. In contrast,
      treatment of HeLa cells with ToxB inhibited EPEC invasion. Thus, Rho, Rac, and
      Cdc42 are not required for assembly of actin pedestals; however, they may be
      involved in EPEC uptake by HeLa cells.

PMID- 9529110
TI  - MrpB functions as the terminator for assembly of Proteus mirabilis mannose
      resistant Proteus-like fimbriae.
AB  - Insertional mutagenesis studies of mrpB, a putative pilin-encoding open reading
      frame of the mrp gene cluster, which encodes mannose-resistant Proteus-like
      (MR/P) fimbriae of Proteus mirabilis, indicate that MrpB functions as the
      terminator for fimbrial assembly.

PMID- 9529111
TI  - Bordetella pertussis filamentous hemagglutinin enhances the immunogenicity of
      liposome-delivered antigen administered intranasally.
AB  - In an attempt to increase the immunogenicity of mucosally delivered antigens, we
      incorporated the Bordetella pertussis filamentous hemagglutinin (FHA) adhesin
      into liposomes containing the glutathione S-transferase of Schistosoma mansoni
      (Sm28GST) as a model antigen. Outbred mice immunized twice intranasally with
      liposomes containing a constant suboptimal dose of Sm28GST and increasing doses
      of FHA produced anti-Sm28GST antibodies in a FHA dose-dependent manner. The
      addition of 3 microg of FHA to the liposomes induced more than 10-fold-higher
      anti-Sm28GST antibody titers, compared to those induced by liposomes without FHA.
      The presence of FHA did not alter the nature of the humoral immune response, and
      the sera contained anti-Sm28GST immunoglobulin G1 (IgG1), IgG2a, and IgG2b.
      However, anti-Sm28GST IgA was only detected when at least 3 microg of FHA was
      added to the preparation. These results show a promising potential for FHA to
      enhance the immunogenicity of mucosally administered antigens incorporated into
      liposomes.

PMID- 9529112
TI  - Expression of multiple pili by Legionella pneumophila: identification and
      characterization of a type IV pilin gene and its role in adherence to mammalian
      and protozoan cells.
AB  - Legionella pneumophila expresses pili of variable lengths, either long (0.8 to
      1.5 microm) or short (0.1 to 0.6 microm), that can be observed by transmission
      electron microscopy. We have identified a gene in L. pneumophila with homology to
      the type IV pilin genes (pilEL). An insertion mutation was constructed in pilEL
      and introduced into the L. pneumophila wild-type strain by allelic exchange. The
      pilin mutant is defective for expression of long pili. Reintroduction of the
      pilin locus on a cosmid vector restores expression of the long pili. The L.
      pneumophila pilEL mutant exhibited approximately a 50% decrease in adherence to
      human epithelial cells (HeLa and WI-26 cells), macrophages (U937 cells), and
      Acanthamoeba polyphaga but had a wild-type phenotype for intracellular
      replication within these cells. Southern hybridization analysis showed that the
      pilEL locus is present in L. pneumophila serogroups 1 through 13 but is variable
      in 16 other Legionella species. The presence of a type IV pilin gene and its
      expression by L. pneumophila may provide an advantage for colonization of lung
      tissues during Legionnaires' disease and invasion of amoebas in the environment.

PMID- 9529113
TI  - Identification and temperature regulation of Legionella pneumophila genes
      involved in type IV pilus biogenesis and type II protein secretion.
AB  - Previously, we had isolated by transposon mutagenesis a Legionella pneumophila
      mutant that appeared defective for intracellular iron acquisition. While
      sequencing in the proximity of the mini-Tn10 insertion, we found a locus that had
      a predicted protein product with strong similarity to PilB from Pseudomonas
      aeruginosa. PilB is a component of the type II secretory pathway, which is
      required for the assembly of type IV pili. Consequently, the locus was cloned and
      sequenced. Within this 4-kb region were three genes that appeared to be organized
      in an operon and encoded homologs of P. aeruginosa PilB, PilC, and PilD, proteins
      essential for pilus production and type II protein secretion. Northern blot
      analysis identified a transcript large enough to include all three genes and
      showed a substantial increase in expression of this operon when L. pneumophila
      was grown at 30 degrees C as opposed to 37 degrees C. The latter observation was
      then correlated with an increase in piliation when bacteria were grown at the
      lower temperature. Southern hybridization analysis indicated that the pilB locus
      was conserved within L. pneumophila serogroups and other Legionella species.
      These data represent the first isolation of type II secretory genes from an
      intracellular parasite and indicate that the legionellae express temperature
      regulated type IV pili.

PMID- 9529114
TI  - Expression of the Candida albicans gene ALS1 in Saccharomyces cerevisiae induces
      adherence to endothelial and epithelial cells.
AB  - To identify genes encoding adhesins that mediate the binding of Candida albicans
      to endothelial cells, a genomic library from this organism was constructed and
      used to transform Saccharomyces cerevisiae. These transformed organisms were
      screened for adherence to endothelial cells, and a highly adherent clone was
      identified. The adherence of this clone to endothelial cells was over 100-fold
      greater than that of control S. cerevisiae transformed with the empty plasmid.
      This clone also exhibited enhanced adherence to epithelial cells. The C. albicans
      gene contained within this clone was found to be ALS1. These results indicate
      that ALS1 may encode a candidal adhesin.

PMID- 9529115
TI  - Human intestinal epithelial cells respond to Cryptosporidium parvum infection
      with increased prostaglandin H synthase 2 expression and prostaglandin E2 and
      F2alpha production.
AB  - Cryptosporidium parvum is an important cause of diarrhea in humans and several
      animal species. Prostaglandins play a central role in regulating intestinal fluid
      secretion in animal models of cryptosporidiosis, but their cellular sources and
      mechanisms of induction are unclear. Here, we show that C. parvum infection
      directly activates prostaglandin H synthase 2 expression and prostaglandin E2 and
      F2alpha production in human intestinal epithelial cells.

PMID- 9529116
TI  - Binding to human extracellular matrix by Neisseria meningitidis.
AB  - Adhesion of Neisseria meningitidis strains to extracellular matrix (ECM) and
      purified matrix components was examined. Most strains bound to subendothelial ECM
      as well as to immobilized fibronectin and types I, III, and V collagen. Strains
      from healthy carriers adhered significantly better than isolates from patients.
      The binding site was localized to the central 75-kDa cell-binding domain of the
      fibronectin molecule. This domain has not been described previously to interact
      with bacterial structures.

PMID- 9529117
TI  - Distribution of protein kinase C isoforms after infection of macrophages with
      Leishmania major.
AB  - We characterized the effects of Leishmania infection on activation-induced
      translocation of protein kinase C (PKC) isoforms in murine bone marrow-derived
      macrophages. Although PKC-dependent gene expression was attenuated by infection,
      the distribution and translocation of PKC isoforms were unaffected. However,
      subsequent dissociation from membranes was substantially delayed for some
      isoforms, particularly PKCbeta.

PMID- 9529118
TI  - Increased leptin expression in mice with bacterial peritonitis is partially
      regulated by tumor necrosis factor alpha.
AB  - Plasma leptin and ob gene mRNA levels were increased in mice following bacterial
      peritonitis, and blocking an endogenous tumor necrosis factor alpha (TNF-alpha)
      response blunted the increase. However, plasma leptin concentrations did not
      correlate with the associated anorexia. We conclude that leptin expression is
      under partial regulatory control of TNF-alpha in peritonitis, but the anorexia is
      not dependent on increased leptin production.

PMID- 9529119
TI  - Granulocytic ehrlichiosis in tick-immune guinea pigs.
AB  - We investigated whether Ixodes scapularis-mediated host immunity interrupts
      transmission of the agent of human granulocytic ehrlichiosis (aoHGE) to guinea
      pigs. Ticks infected with aoHGE readily transmitted aoHGE to tick-immune guinea
      pigs, despite incomplete tick engorgement and host attachment. Although tick
      immunity can prevent Lyme borreliosis, protection is not afforded against
      granulocytic ehrlichiosis.

PMID- 9529120
TI  - Trafficking of porin-deficient Salmonella typhimurium mutants inside HeLa cells:
      ompR and envZ mutants are defective for the formation of Salmonella-induced
      filaments.
AB  - Outer membrane porin genes of Salmonella typhimurium, including ompC, ompF, and
      tppB, are regulated by the products of ompB, a two-component regulatory locus
      encoding OmpR and EnvZ. S. typhimurium ompR mutants are attenuated in mice, but
      to date no one has studied the intracellular trafficking of S. typhimurium porin
      deficient mutants. In this study, isogenic transposon mutants of S. typhimurium
      with insertions in ompR, envZ, ompF, ompC, ompD, osmZ, and tppB were compared
      with wild-type SL1344 for trafficking in the human epithelial cell line HeLa. We
      found that ompR and envZ mutants were reduced or completely inhibited for the
      formation of Salmonella-induced filaments (Sifs). This result was confirmed with
      an ompB deletion mutant. Sifs are tubular structures containing lysosomal
      glycoprotein which are induced specifically by intracellular Salmonella. Genetic
      analysis showed that the ompR mutation could be complemented in trans by cloned
      ompR to restore its ability to induce Sifs. In contrast, mutations in the known
      ompR-regulated genes ompF, ompC, and tppB (as well as the ompR-independent porin
      gene, ompD) had no effect on Sif formation relative to that of wild-type SL1344,
      thus indicating that OmpR does not exert its role on these genes to induce Sif
      formation. The omp mutants studied were able to invade and replicate in HeLa
      cells at levels comparable to those in wild-type SL1344. We conclude that OmpR
      and EnvZ appear to regulate Sif formation triggered by intracellular S.
      typhimurium.

PMID- 9529121
TI  - Alfa-interferon in the treatment of essential thrombocythemia: clinical results
      and evaluation of its biological effects on the hematopoietic neoplastic clone.
      Italian Cooperative Group on ET.
AB  - The efficacy of alfa-interferon (alfa-IFN) in essential thrombocythemia (ET)
      patients has been reported by several authors. The aim of this study is to assess
      the magnitude of the effect of alfa-IFN on the neoplastic clone. As of December
      1993, 11 ET patients received alfa-IFN at a dose of 3-6 MU/s.c./day for 6 months.
      Ten of 11 obtained complete hematological remission (CHR) and one achieved
      partial hematological remission. Megakaryocyte concentration was reduced in six
      cases. The spleen,which was enlarged in four patients, decreased in size in two
      patients. Seven of eight patients who were symptomatic at diagnosis obtained
      resolution of symptoms. In order to obtain indications about the structural
      modifications induced by alfa-IFN in ET megakaryocytes (Mks), Fourier-transform
      infra-red microspectroscopy analysis performed on 10 single Mks of each patient,
      was done in seven of 11 patients; the analysis showed a reduction of A1/A2 ratios
      (A1 integrated area of the band at 1080 cm(-1) due to the nucleic acids
      absorption; A2 integrated area of the band at 1540 cm(-1) due to proteic
      components absorption) in five cases, and in three of these five patients A1/A2
      ratios achieved normal values. After alfa-IFN treatment we did not observe any
      change in the methylation pattern of DNA from the granulocyte fraction. Our
      results confirm the efficacy of alfa-IFN in ET patients, and the decrease of
      A1/A2 ratios in several patients is a demonstration of the depth of the effect of
      alfa-IFN on the neoplastic clone. The results of clonality studies showed the
      persistence of clonal hematopoiesis. Whether higher alfa-IFN dose and/or more
      prolonged alfa-IFN therapy may allow a restoration of polyclonal hematopoiesis
      remains to be determined and should be explored in future clinical trials.

PMID- 9529122
TI  - Serum thrombopoietin levels in patients correlate inversely with platelet counts
      during chemotherapy-induced thrombocytopenia.
AB  - We studied serum thrombopoietin (TPO) levels and circulating numbers of platelet
      during five courses of myelosuppressive post-remission chemotherapy in three
      patients with acute leukemia in complete remission. Serum TPO levels were
      measured by a newly developed and sensitive sandwich enzyme-linked immunosorbent
      assay. In all courses, serum TPO levels changed reciprocally with the platelet
      counts. When platelets were transfused into patients near the time of platelet
      nadir, the TPO levels dropped temporarily, while platelet counts temporarily
      increased. In addition, platelets obtained after transfusion in a
      thrombocytopenic patient showed lower binding to biotinylated TPO than donor
      platelets prior to the transfusion. The finding indicated that the TPO receptors
      were saturated with endogenous TPO of the patient with a high serum TPO level.
      These results suggest that the platelet mass directly regulates serum TPO levels
      by receptor-mediated absorption and is one of the major regulators of serum TPO
      levels in humans.

PMID- 9529123
TI  - FLT3 signaling in hematopoietic cells involves CBL, SHC and an unknown P115 as
      prominent tyrosine-phosphorylated substrates.
AB  - Proliferation and survival of hematopoietic progenitors are partially dependent
      on the interaction between the FLT3 receptor tyrosine kinase (RTK) and its
      ligand, FL. This biological function depends primarily on tyrosine
      phosphorylation of cellular targets that initiate several transduction cascades.
      These events return to their basal levels upon activation of specific
      phosphatases. We analyzed tyrosine phosphorylation events in response to FL, in
      human cell lines of different hematopoietic origins that express endogenous FLT3,
      namely the myelomonocytic, monocytic, pre-B and pro-B lineages. This study aimed
      at determining (1) the identity of FLT3 downstream substrates in physiologically
      relevant cells and (2) distinct substrate involvement in myeloid or early B
      cells. The two prominent tyrosine-phosphorylated proteins are p52SHC and p115CBL
      in myeloid cell lines and p52SHC and an uncharacterized p115 in early B cell
      lines. Following FL stimulation, a concomitant increase in both CBL
      phosphorylation and complex formation with p85 subunit of phosphatidylinositol 3'
      kinase is observed. In contrast, the GRB2/CBL association observed in
      unstimulated cells is not modified after stimulation, and SHC is never detected
      in anti-CBL immunoprecipitates. FL-inducible binding of CBL to the CRKII adaptor
      molecule is also demonstrated. This study presents a picture of the signaling
      events triggered by activation of endogenous FLT3 receptor in human hematopoietic
      cells, including the existence of a B cell-specific FLT3 substrate.

PMID- 9529124
TI  - Increased DNA methyltransferase expression in leukaemia.
AB  - Aberrant DNA methylation has been observed consistently in many human tumours, in
      particular in the CpG islands of tumour suppressor genes, but the underlying
      mechanism of these changes remains unclear. To determine whether DNA
      methyltransferase expression is increased in leukaemia, we developed a
      standardised competitive RT-PCR assay to measure the level of DNA
      methyltransferase transcripts. Using this assay on bone marrow RNA samples from
      12 patients with acute leukaemia, we observed a 4.4-fold mean increase in the
      level of DNA methyltransferase mRNA compared with normal bone marrow. These
      results support but do not prove the hypothesis that an increase in DNA
      methyltransferase activity is associated with malignant haematological diseases
      and may constitute a key step in carcinogenesis.

PMID- 9529125
TI  - Acute myeloid leukemia with 11q23 translocations: myelomonocytic immunophenotype
      by multiparameter flow cytometry.
AB  - 11q23 translocations (t(11q23)) are recurring cytogenetic abnormalities in both
      acute myeloid leukemia (AML) and acute lymphoblastic leukemia, involving the same
      gene, ALL1 (or MLL). Mixed lineage antigen expression has been reported in these
      leukemias, but its frequency and clinical significance are unknown. We
      immunophenotyped leukemia cells from 19 adult de novo AML patients with t(11q23)
      by multiparameter flow cytometry. Translocations included t(6;11)(q27;q23),
      t(9;11)(p22;q23), t(9;11;19)(p22;q23;q13.3), t(2;11)(11;17)(q37;q11q23;q11),
      t(11;17)(q23;q25), t(11;19)(q23;p13.1), t(11;19)(q23;p13.3) and
      t(11;22)(q23;q11). FAB types were M4 and M5. The committed stem cell and myeloid
      antigens HLADr, CD4dim, CD11b, CD13, CD15, CD32, CD33, CD38 and CD64 were each
      expressed in 80-100% of cases, and the early stem cell and lymphoid antigens
      CD34, CD56, CD3, CD2 and CD7 in 42, 39, 16, 5 and 5%, respectively. Antigen
      expression frequencies did not differ from those in 443 adequately karyotyped M4
      and M5 cases without t(11q23). Fifteen patients (79%) attained complete remission
      (CR); median CR duration and survival were 10.0 and 15.1 months. CR duration and
      survival did not correlate with antigen expression. In particular, patients with
      t(9;11) survived longer than those with other t(11q23) (median not reached vs 7.6
      months; P = 0.048), but antigen expression did not differ in the two groups. Thus
      frequencies of lymphoid antigen expression are similar in AML with t(11q23) and
      in other FAB M4 and M5 cases, treatment outcome does not differ in t(11q23) cases
      with and without lymphoid antigen expression, and better outcome of patients with
      t(9;11) compared to other t(11q23) does not correlate with differences in antigen
      expression. Mixed lineage antigen expression is not a distinctive feature of AML
      with t(11q23).

PMID- 9529126
TI  - Identification of several genes differentially expressed during progression of
      chronic myelogenous leukemia.
AB  - The Bcr-Abl fusion protein plays a crucial role in the initiation and maintenance
      of chronic myelogenous leukemia (CML). However, additional events are necessary
      for the transition from the chronic phase to the terminal phase of the disease.
      To identify genes involved in the disease progression, we constructed a
      subtractive library from enriched K562 cell mRNA. We obtained 1084 cDNA clones.
      After a specific hybridization of these clones with a cDNA probe from either
      chronic phase or K562 cells, 43 clones which present a differential hybridization
      level have been selected. Among them, several clones corresponded to ribosomal
      protein genes showing an increased transcription level during the blast crisis.
      We observed variations in the expression of a cellular adhesion molecule, a
      laminin-binding protein. An increased transcription level of the MAZ gene has
      been shown in the terminal phase of the disease. This gene encodes a protein that
      regulates the transcription of myc.

PMID- 9529128
TI  - Characterization of the erythropoiesis in myelodysplasia by means of ferrokinetic
      studies, in vitro erythroid colony formation and soluble transferrin receptor.
AB  - In refractory anemia (RA) and refractory anemia with ringed sideroblasts (RARS) a
      discrepancy is observed between the decreased in vitro erythroid colony formation
      and the normal or increased number of normoblasts in the bone marrow. To study
      the in vivo and in vitro erythropoiesis in more detail erythron transferrin
      uptake (ETU), soluble transferrin receptor (sTfR) and erythroid in vitro colony
      formation were performed in 24 patients with RA and five patients with RARS.
      These results were correlated with bone marrow morphology and transfusion
      dependency. Increased (mean, 124.9; range, 74-225 micromol/l blood/day) and
      normal (mean, 60.6; range, 50-71) ETU values were observed in 51% and 28% of the
      cases, whereas 21% of the cases demonstrated a diminished ETU value (mean, 35.8;
      range, 28-46), which correlated significantly with sTfR in cases with RA (P <
      0.05, r = 0.64). A significant difference in ETU values was observed between RA
      (mean, 77.6; range, 28-189) and RARS (mean, 144.0; range, 59-225, P < 0.05). Most
      of the cases (73%) with increased ETU values showed an augmented percentage of
      erythroblasts in the bone marrow, which was inversely related with the serum Epo
      levels (P < 0.05, r = 0.51). However no correlation was found between the ETU
      values and the in vitro erythroid colony formation. Transfusion dependency was
      associated with normal to increased ETU levels (P < 0.05) and cytogenetic
      abnormalities (P < 0.05). These observations demonstrate that different patterns
      of defects can be observed in the erythropoiesis of RA and RARS patients whereby
      normal to increased ETU levels and the presence of cytogenetic abnormalities
      differentiate between cases of RA with ineffective erythropoiesis associated with
      regular transfusions and cases who are relatively transfusion independent.

PMID- 9529127
TI  - Quality of IL-3 and G-CSF-mobilized peripheral blood stem cells in patients with
      early chronic phase CML.
AB  - Coexistence of Philadelphia chromosome (Ph)-negative, primitive hematopoietic
      progenitor cells with their malignant counterparts in chronic myelogenous
      leukemia (CML) has been reported. As most of the Ph-negative progenitor cells do
      not express the HLA-DR antigen, selection of them might be possible. Peripheral
      blood progenitor cells (PBPC) from eight early chronic phase (CML) patients were
      mobilized by ICE chemotherapy followed by simultaneous administration of
      recombinant human granulocyte colony-stimulating factor (rhG-CSF) and recombinant
      human interleukin 3 (rhIL-3). PBPCs were collected by leukapheresis in the early
      phase of hematopoietic recovery after chemotherapy, CD34 selected and cultured in
      vitro. The content of Ph chromosome-positive cells in leukapheresis products as
      well as after CD34 enrichment and after in vitro culture was analyzed by
      interphase fluorescence in situ hybridization (FISH) and RT-PCR. The percentage
      of Ph chromosome-positive PBPC was reduced after each purification step in almost
      all samples. A substantial number of PBPC samples were negative for the bcr/abl
      mRNA rearrangement as analyzed by RT-PCR. The present study demonstrates the
      feasibility of mobilizing Ph-negative PBPC during the early phase of
      hematopoietic recovery after ICE chemotherapy and simultaneous administration of
      rhIL-3 and rhG-CSF.

PMID- 9529130
TI  - The biological consequences of excess GM-CSF levels in transgenic mice also
      lacking high-affinity receptors for GM-CSF.
AB  - GM-CSF transgenic mice were crossed with mice with homozygous inactivation of the
      gene encoding the common beta chain (beta c) of the GM-CSF receptor to produce
      mice with constitutively elevated GM-CSF levels but no high-affinity GM-CSF
      receptors. GM-CSF transgenic beta c -/- mice had exceptionally elevated serum GM
      CSF levels but failed to develop the abnormal peritoneal cell population, eye
      destruction or tissue lesions characteristic of GM-CSF transgenic beta c +/+
      mice. The alveolar proteinosis of beta c -/- mice was not altered in GM-CSF
      transgenic beta c -/- mice. Levels of GM-CSF mRNA in transgenic GM-CSF beta c -/-
      were elevated but lower than in transgenic beta +/+ mice and the higher serum GM
      CSF levels were traced in part to the longer serum half-life of GM-CSF in beta c 
      /- than in beta c +/+ mice although urinary loss of GM-CSF was higher in beta c 
      /- than in +/+ mice. The data indicate that the transgenic phenotype was due to
      stimulation by GM-CSF and not an insertional effect, that low-affinity receptors
      are not capable of initiating tissue pathology even in the presence of excess GM
      CSF levels and that autocrine production of GM-CSF by GM-CSF-responsive cells
      also fails to induce changes in these cells. The results support current dogma
      that the action of polypeptide regulators is mediated exclusively by activation
      of high-affinity membrane receptors.

PMID- 9529129
TI  - Etoposide and antimetabolite pharmacology in patients who develop secondary acute
      myeloid leukemia.
AB  - Etoposide, an effective agent for acute lymphoblastic leukemia (ALL), can cause
      secondary acute myeloid leukemia (AML) in a subset of patients. Our objectives
      were to determine whether patients who develop secondary AML displayed altered
      etoposide pharmacokinetics or other pharmacologic characteristics compared to
      identically treated patients who did not develop AML. Children with newly
      diagnosed ALL were treated according to a protocol which included etoposide 300
      mg/m2 given three times over 8 days during remission induction and once every 2-4
      weeks during 120 weeks of continuation therapy. Characteristic 11q23
      rearrangements were documented in seven of the eight patients with AML. Etoposide
      clearance, time that etoposide concentrations exceeded 10 microM, etoposide or
      etoposide catechol area-under-the-plasma-concentration vs time curve (AUC), serum
      albumin, and average methotrexate concentration did not differ significantly
      between the two groups; thiopurine methyltransferase (TPMT) activity tended to be
      lower in the eight children who did vs the 23 matched control children who did
      not develop AML (P=0.16). Further regression analyses likewise indicated that
      lower TPMT activity tended to be associated with shorter onset of secondary AML
      (P=0.11); it also tended to be lower among the eight index cases compared to the
      entire unmatched cohort of 105 identically treated children with ALL (P=0.10). We
      observed no statistically significant differences in etoposide disposition and
      antimetabolite pharmacology between patients who did and did not develop
      secondary AML.

PMID- 9529131
TI  - Regulation of p100 (NFKB2) expression in human monocytes in response to
      inflammatory mediators and lymphokines.
AB  - The transcription factor NF-kappaB plays an important role in the regulated
      expression of cytokines in human monocytes. A p100 subunit of NF-kappaB has
      IkappaB-like properties by sequestering the p65 transactivating subunit in the
      cytosol of cells. In transient transfection assays we demonstrated that p100 has
      an inhibitory effect on the NF-kappaB-dependent IL-6 promoter activity. In view
      of this finding, we studied the regulation of the p100 subunit in human monocytes
      in response to LPS, the inflammatory cytokines IL-1beta and TNF-alpha and
      lymphokines. The results demonstrate that LPS, IL-1beta, and TNF-alpha induce
      p100 expression at mRNA and protein level while IFN-gamma, IL-3 and IL-4/IL-10
      have no effect. The induction of p100 expression was shown to be mediated by a
      two-fold increase in the p100 transcription rate and a two-fold increase in p100
      mRNA stability. Furthermore the p100 mediated upregulation was dependent on a
      tyrosine kinase dependent pathway rather than the protein kinase C pathway. NF
      kappaB is a complex of either p50 homodimers or a p50/p65 heterodimer. The latter
      is known to strongly autoregulate p100 transcription. We therefore examined the
      composition of NF-kappaB induced by LPS vs the different lymphokines. LPS-induced
      NF-kappaB showed a distinct p65 supershift whereas the composition of NF-kappaB
      induced by different lymphokines did not show a change in p65. We conclude that
      the p100 subunit of the transcription factor NF-kappaB is induced by different
      inflammatory mediators while lymphokines fail to induce p100 expression which may
      be caused by the induction of NF-kappaB predominantly consisting of p50
      homodimers.

PMID- 9529132
TI  - The role of insulin (INS) and insulin-like growth factor-I (IGF-I) in regulating
      human erythropoiesis. Studies in vitro under serum-free conditions--comparison to
      other cytokines and growth factors.
AB  - The role of insulin (INS), and insulin-like growth factor-I (IGF-I) in the
      regulation of human erythropoiesis is not completely understood. To address this
      issue we employed several complementary strategies including: serum free cloning
      of CD34+ cells, RT-PCR, FACS analysis, and mRNA perturbation with
      oligodeoxynucleotides (ODN). In a serum-free culture model, both INS and IGF-I
      enhanced survival of CD34+ cells, but neither of these growth factors stimulated
      their proliferation. The influence of INS and IGF-I on erythroid colony
      development was dependent on a combination of growth factors used for stimulating
      BFU-E growth. When BFU-E growth was optimally stimulated with erythropoietin
      (EpO) + kit ligand (KL) the large erythroid colonies developed normally even in
      the absence of INS or IGF-I. However, the addition of both of these growth
      factors slightly enhanced colony size. On the other hand, if erythroid colonies
      were stimulated suboptimally with EpO + IL-3 only, INS or IGF-I increased the
      number of small erythroid bursts by approximately 30%. Both INS and IGF-I
      activated signal transduction in maturing human erythropoietic cells as
      determined by phosphorylation of the insulin receptor substrate-2 (IRS-2)
      protein. We also found by RT-PCR that mRNA coding for INS-R is expressed in FACS
      sorted CD34+, c-kit-R+ marrow cells, and in cells isolated from BFU-E and CFU-GM
      colonies. Expression of INS-R protein on these cells was subsequently confirmed
      by cytofluorometry. In contrast, the receptor for insulin-like growth factor-I
      (IGF-IR) was not detected on CD34+ cells, and was first easily detectable on more
      differentiated cells derived from day 6 BFU-E and CFU-GM colonies. We conclude
      that INS and IGF-I may be survival factors for human CD34+ cells, but are not
      required during early erythropoiesis. In contrast, both growth factors may play
      some role at the final stages of erythroid maturation.

PMID- 9529133
TI  - Leukemic cells with 11q23 translocations express granulocyte colony-stimulating
      factor (G-CSF) receptor and their proliferation is stimulated with G-CSF.
AB  - We report a 20-month-old boy with acute lymphoblastic leukemia with the 11q23
      translocation whose blasts markedly increased in peripheral blood after
      intravenous granulocyte colony-stimulating factor (G-CSF) administration, but
      disappeared after stopping G-CSF. The in vitro study showed that the leukemic
      cells separated from this patient expressed G-CSF receptor (G-CSFR) and an
      addition of G-CSF stimulated their proliferation by 3H-thymidine incorporation
      assay (stimulation index, 4.9). To clarify whether or not leukemic cells with
      11q23 translocations generally express G-CSFR and show proliferative response to
      G-CSF, we performed the similar in vitro experiments using eight leukemic cell
      lines with 11q23 translocations. We found that all cell lines examined expressed
      G-CSFR (20-98%) and proliferation of seven leukemic cell lines was significantly
      enhanced in response to G-CSF (stimulation index >1.5 in five cell lines),
      suggesting a possible participation of the G-CSF/G-CSFR interaction in the
      process of growth regulation of leukemic cells with 11q23 translocations.

PMID- 9529134
TI  - Fluorescence in situ hybridization analyses of hematologic malignancies reveal
      frequent cytogenetically unrecognized 12p rearrangements.
AB  - Thirty-two hematologic malignancies--nine with cytogenetically identified 12p
      abnormalities and 23 with whole or partial losses of chromosome 12--were selected
      for fluorescence in situ hybridization (FISH) investigations of 12p. These
      analyses revealed structural 12p changes, such as translocations, deletions,
      insertions, inversions and amplification, in 20 cases. ETV6 rearrangements were
      detected in three acute leukemias. One acute undifferentiated leukemia had
      t(4;12)(q12;p13) as the sole anomaly. The second case, an acute myeloid leukemia
      (AML), displayed complex abnormalities involving, among others, chromosomes 9 and
      12. The third case, also an AML, had an insertion of the distal part of ETV6 into
      chromosome arm 11q and into multiple ring chromosomes, which also contained
      chromosome 11 material, resulting in an amplification of a possible fusion gene.
      The fusion partners in these cases remain to be identified. Thirty-one additional
      breakpoints on 12p could be characterized in detail. The majority of these breaks
      were shown to result in interchromosomal rearrangements, possibly indicating the
      location of hitherto unrecognized genes of importance in the pathogenesis of
      hematologic malignancies. The FISH analyses disclosed terminal or interstitial
      12p deletions in 18 cases. Seven myeloid malignancies showed deletions restricted
      to a region, including ETV6 and CDKN1B, which has been reported to be frequently
      lost in leukemias. In four cases, the deletions involved both these genes,
      whereas two AML displayed loss of CDKN1B but not ETV6, supporting previously
      reported findings indicating a region of deletion not including this gene.
      However, one myelodysplastic syndrome lacked one copy of ETV6 but not CDKN1B.
      Hence, we suggest a minimal region of deletion on 12p located between the ETV6
      and CDKN1B genes.

PMID- 9529135
TI  - Immunotherapy against murine leukemia.
AB  - The central hypothesis underlying specific anti-leukemia immunotherapy is that
      leukemic cells express antigenic determinants not expressed on their counterpart
      normal adult cells. We have developed a murine myeloid leukemia/tumor
      immunization model using the low-immunogenic WEHI3 leukemia in syngeneic mice.
      Mice preimmunized with irradiated, transduced IL-7-producing WEHI3 cells showed
      systemic protection and rejection of a lethal dose of intravenously (i.v.)
      injected parental WEHI3 cells (5 x 10(4)) with 40% long-term survival. When
      vaccinated with a mixture of parental WEHI3 cells and IL-2-producing NIH-3T3
      fibroblasts (5 x 10(5)), 60% survival was observed. Vaccination with murine
      granulocyte-macrophage colony-stimulating factor (GM-CSF)-producing WEHI3 cells
      resulted in only 20% survival of i.v. challenged mice, and the additional
      combination of IL-2- and IL-7-producing vaccine did not reveal any additive or
      synergistic effects. Immunizing mice with a pre-established leukemia burden
      (injected with 5 x 10(4) WEHI3 cells, i.v., 3 days prior to immunization) did not
      cure or result in a prolongation of survival, indicating that improved methods of
      immunization are needed. Taken together, we have identified IL-7 and IL-2 as
      effective cytokines in our leukemia/vaccination model with only marginal activity
      by GM-CSF.

PMID- 9529136
TI  - Involvement of the glucocorticoid receptor in stress-induced apoptosis of
      leukemic cells.
AB  - Glucocorticoid (GC) hormones induce apoptosis in lymphoid and leukemic cells by
      binding and activating cytosolic GC receptors. Because physiological stress often
      causes hormone-free GC receptor activation, we have investigated if stress
      induced apoptosis of lymphoid cells is also mediated by the activation of the GC
      receptor pathway. In S49 T lymphoma cells, heat shock and deprivation of growth
      factors or nutrients caused nuclear translocation and loss of agonist binding
      capacity of GC receptors, similar to that in cells incubated with the
      glucocorticoid dexamethasone (DEX). In variant S49 H.2 cells, cross-resistance to
      DEX, temperature shocks and growth factor deprivation were associated with a
      higher threshold for hormone-dependent and -independent receptor activation in
      situ and with impaired in vitro activation of cytosolic receptors. Cross
      resistance to DEX, low serum and heat shock was abrogated, however, by
      pharmacological sensitization of GC receptor activation with the drug meta
      iodobenzylguanidine (MIBG). Sensitive S49 cells and resistant variants did not
      differ in the expression levels of the apoptosis-regulating genes bax, bad, bcl-X
      and bcl-2, the status of the p53 gene nor in a different requirement for the
      growth factors II-2, IL-4 or IL-9. The results suggest that ligand-independent
      activation of the GC receptor is a central signalling and controlling event in
      some forms of stress-induced apoptosis, assigning a novel function to the GC
      receptor in the regulation of lymphoid and leukemic cell numbers.

PMID- 9529137
TI  - MUC18, a member of the immunoglobulin superfamily, is expressed on bone marrow
      fibroblasts and a subset of hematological malignancies.
AB  - Despite the importance of bone marrow stromal cells in hemopoiesis, the profile
      of surface molecule expression is relatively poorly understood. Mice were
      immunized with cultured human bone marrow stromal cells in order to raise
      monoclonal antibodies to novel cell surface molecules, which might be involved in
      interactions with hemopoietic cells. Three antibodies, WM85, CC9 and EB4 were
      produced, and were found to identify a 100-110 kDa antigen on bone marrow
      fibroblasts. Molecular cloning revealed the molecule to be MUC18 (CD146), a
      member of the immunoglobulin superfamily, previously described as a marker of
      metastatic melanoma. In addition to the expected expression on melanoma cell
      lines and endothelial cells, a number of human leukemic cell lines were found to
      express MUC18, including all six T leukemia lines tested, one of five B lineage
      lines and one of four myeloid lines. Analysis of bone marrow samples from
      patients revealed positivity in 20% of B lineage ALL (n = 20), one of three T
      ALL, 15% of AML (n = 13) and 43% of various B lymphoproliferative disorders (n =
      7). No apparent reactivity was observed with mononuclear cells from normal
      peripheral blood or bone marrow, including candidate hemopoietic stem cells
      characterized by their expression of the CD34 antigen. However, positive
      selection of bone marrow mononuclear cells labeled with MUC18 antibody revealed a
      rare subpopulation (<1%) containing more than 90% of the stromal precursors
      identified in fibroblast colony-forming assays. The structure and tissue
      distribution of MUC18 suggest a functional role in regulation of hemopoiesis.

PMID- 9529138
TI  - Bolus vincristine and epirubicin with cyclophosphamide and dexamethasone (VECD)
      as induction and salvage treatment in multiple myeloma.
AB  - The VAD regimen (infusional vincristine, doxorubicin and intermittent high-dose
      dexamethasone) is widely considered the standard salvage chemotherapy for
      multiple myeloma resistant to alkylating agents and is increasingly used for
      induction in previously untreated patients prior to high-dose chemotherapy. We
      investigated the VECD protocol, a VAD-based regimen using bolus injections of
      vincristine 1.5 mg day 1 and epirubicin 20 mg/m2 days 2 and 3 with 1 h infusions
      of cyclophosphamide 200 mg/m2 days 1-3 and oral dexamethasone 20 mg/m2 days 1-5
      as induction and salvage treatment in multiple myeloma. Fifteen previously
      untreated and 25 patients with relapsed or refractory myeloma were included.
      Cycles were repeated every 3 weeks. In the group of previously untreated patients
      the response rate was 53% and the median survival has not been reached at 59
      months. For relapsed and refractory patients the response rate was 44% and the
      median survival 13 months. In the group of patients with truly refractory disease
      on prior chemotherapy a response rate of 47% was achieved, which appears superior
      to the results observed for VAD alone. The main toxicities were leukocytopenia
      WHO grade IV and infections grade III/IV with both toxicities being significantly
      more pronounced in pretreated patients. VECD appears to be an effective regimen
      for induction and salvage therapy in multiple myeloma. Based on the limited
      number of patients treated the results are comparable to those reported for VAD,
      with the advantage that the infusional application of vincristine and the
      anthracycline is omitted.

PMID- 9529139
TI  - Detection of hyperdiploid karyotypes (>50 chromosomes) in childhood acute
      lymphoblastic leukemia (ALL) using fluorescence in situ hybridization (FISH).
AB  - ALL patients with a hyperdiploid karyotype of more than 50 chromosomes (high
      hyperdiploidy) carry a better prognosis in contrast to patients presenting with
      other cytogenetic features, and an appropriate less intensive therapy protocol
      should be developed for these patients. For this reason it is desirable to have a
      quick screening method identifying those with this type of hyperdiploidy. We
      therefore studied the bone marrow and/or blood cells of 278 children with ALL
      using double target fluorescence in situ hybridization (FISH) on interphase. A
      combination of DNA probes (repetitive, centromere specific) was applied detecting
      chromosomes which are most frequently overrepresented in patients with
      hyperdiploidy (>50), at chromosomes 6, 10, 17 and 18. All patients showing
      hybridization signals differing from the normal signal distribution of two spots
      for each tested chromosome were analyzed cytogenetically as well. 102 children
      (102/278; 36.7%) were found to have a clone with aberrant FISH results. In 80
      patients (80/278, 28.8%) the cytogenetic analysis detected a hyperdiploid
      karyotype >50 chromosomes, whereas the remaining patients (n=12) could be related
      to other ploidy subgroups, ie hyperdiploidy with 47-50 chromosomes, haploidy,
      triploidy/tetraploidy. Comparison of the FISH results with the measurements of
      the DNA content showed good agreement for 88.8% (208/234) of the investigated
      patients. The detected rate of 28.8% patients with a high hyperdiploid karyotype
      in our investigated cohort is comparable to the frequency of other studies. Only
      one patient was not identified as having a hyperdiploid karyotype with our
      combination of DNA probes. Our results indicate that FISH is a feasible and quick
      screening method for the detection of hyperdiploid karyotypes (>50 chromosomes)
      and other ploidy subgroups.

PMID- 9529140
TI  - Reverse transcription polymerase chain reaction is a reliable assay for detecting
      leukemic colonies generated by chronic myelogenous leukemia cells.
AB  - Single-colony karyotyping (SCK) and reverse-transcription polymerase chain
      reaction (RT-PCR) are two increasingly used techniques for the quantification of
      leukemic colonies generated by chronic myelogenous leukemia (CML) cell fractions
      purged or selected in vitro. Recently, the existence of Philadelphia (Ph)
      chromosome positive progenitors with a silent BCR-ABL gene has been reported,
      thus raising concerns on the use of RT-PCR for detecting BCR-ABL positive
      progenitors. In order to investigate this issue further, colonies (n = 204)
      generated by mononuclear (MNC) or CD34+ CML cells were individually harvested,
      divided into two aliquots and analyzed both at the cytogenetic level to detect
      the Ph chromosome, and the molecular level to detect BCR-ABL transcripts. The
      mean (+/- s.d.) percentages of colonies analyzable by either SCK or RT-PCR were
      74 +/- 16% and 86 +/- 16%, respectively. A significant percentage of colonies (67
      +/- 19%) could be successfully analyzed by both SCK and RT-PCR. Although the
      majority of these colonies (97 +/- 5%) were Ph-positive and BCR-ABL-positive, a
      negligible percentage (4%) of progenitors were Ph-positive but BCR-ABL-negative.
      In order to test the influence of colony size on the outcome of molecular
      analysis, the efficiency of our RT-PCR assay in detecting BCR-ABL transcripts was
      investigated by means of experiments in which the number of cells used to start
      RNA extraction was serially reduced. These experiments showed that at least 150
      cells were necessary to achieve a reproducible amplification of BCR-ABL
      transcripts. By correlating the size of harvested colonies with the outcome of
      molecular analysis, it was evident that BCR-ABL-negative but Ph-positive colonies
      represented false negative results occurring when a number of leukemic cells
      below the detection limit of our RT-PCR assay was analyzed. In conclusion, our
      data demonstrate that individual CML colonies grown in semisolid culture assays
      can be indifferently analyzed by SCK or RT-PCR, and support an extensive use of a
      carefully standardized RT-PCR assay to estimate the leukemic burden within
      samples which have been purged and selected in vitro.

PMID- 9529141
TI  - Acute promyelocytic leukemia following mitoxantrone as single agent for the
      treatment of multiple sclerosis.

PMID- 9529142
TI  - The first report of a Philadelphia chromosome and BCR/ABL rearrangement positive
      myeloproliferative disorder in a child with thrombocythemia.

PMID- 9529143
TI  - Discordant erythropoiesis in CML.

PMID- 9529145
TI  - Cytokines induce the development of functionally heterogeneous T helper cell
      subsets.

PMID- 9529144
TI  - New understanding of the pathogenesis of CML; a prototype of early neoplasia by
      Dr Bayard Clarkson and colleagues.

PMID- 9529146
TI  - A stage-specific enhancer of immunoglobulin J chain gene is induced by
      interleukin-2 in a presecretor B cell stage.
AB  - Interleukin-2 (IL-2)-induced transcription of the J chain gene was used as a
      model for analyzing cytokine regulation during B cell development. To determine
      whether IL-2 signals are targeted to a J chain gene enhancer as well as to its
      promoter, the sequences flanking the J chain gene were first examined for DNase I
      hypersensitivity. Of six sites identified, two strong ones, 7.5 kb upstream of
      the J chain gene, were found to be associated with an enhancer that is active
      only during the antigen-driven stages of B cell development. Further analyses of
      the enhancer in the IL-2-responsive presecretor BCL1 cells showed that the
      enhancer is activated at this stage by an IL-2 signal that functions by opening
      the enhancer chromatin and stimulating STAT5 to bind to a STAT5 element critical
      for the enhancer induction. Moreover, after this early induction stage, the
      enhancer was shown to be constitutively open and active in terminally
      differentiated plasma cells.

PMID- 9529147
TI  - The death domain kinase RIP mediates the TNF-induced NF-kappaB signal.
AB  - The death domain serine/threonine kinase RIP interacts with the death receptors
      Fas and tumor necrosis receptor 1 (TNFR1). In vitro, RIP stimulates apoptosis,
      SAPK/JNK, and NF-kappaB activation. To define the physiologic role(s) that RIP
      plays in regulating apoptosis in vivo, we introduced a rip null mutation in mice
      through homologous recombination. RIP-deficient mice appear normal at birth but
      fail to thrive, displaying extensive apoptosis in both the lymphoid and adipose
      tissue and dying at 1-3 days of age. In contrast to a normal thymic anti-Fas
      response, rip-/- cells are highly sensitive to TNFalpha-induced cell death.
      Sensitivity to TNFalpha-mediated cell death in rip-/- cells is accompanied by a
      failure to activate the transcription factor NF-kappaB.

PMID- 9529148
TI  - Crystal structure of I-Ak in complex with a dominant epitope of lysozyme.
AB  - We have determined the structure of murine MHC class II I-Ak in complex with a
      naturally processed peptide from hen egg lysozyme (HEL residues 50-62) at 1.9 A
      resolution. These results provide a structural basis for the I-Ak peptide-binding
      motif. Binding is established by the deep burial of five anchor side chains into
      specific pockets of the I-Ak binding groove, with a zen-like fit of an aspartic
      acid in the P1 pocket. We also show that in the I-Ak alpha chain, a bulge occurs
      in the first strand of the peptide-binding platform, an insertion probably common
      to all I-A and HLA-DQ alleles. The I-Ak beta chain has a deletion in the helical
      region adjacent to the P7 pocket and an insertion in the helical region
      neighboring the P1 pocket. As a result of these structural features, the extended
      HEL peptide dips low into the center of the I-Ak groove and reaches toward
      solvent at its C-terminal end.

PMID- 9529149
TI  - Crystal structures of two I-Ad-peptide complexes reveal that high affinity can be
      achieved without large anchor residues.
AB  - We have determined the structures of I-Ad covalently linked to an ovalbumin
      peptide (OVA323-339) and to an influenza virus hemagglutinin peptide (HA126-138).
      The floor of the peptide-binding groove contains an unusual beta bulge, not seen
      in I-E and DR structures, that affects numerous interactions between the alpha
      and beta chains and bound peptide. Unlike other MHC-peptide complexes, the
      peptides do not insert any large anchor residues into the binding pockets of the
      shallow I-Ad binding groove. The previously identified six-residue "core" binding
      motif of I-Ad occupies only the P4 to P9 pockets, implying that specificity of T
      cell receptor recognition of I-Ad-peptide complexes can be accomplished by
      peptides that only partially fill the MHC groove.

PMID- 9529150
TI  - Molecular interaction of CD1b with lipoglycan antigens.
AB  - The ability of human CD1b molecules to present nonpeptide antigens is suggested
      by the T cell recognition of microbial lipids and lipoglycans in the presence of
      CD1b-expressing antigen-presenting cells. We demonstrate the high-affinity
      interaction of CD1b molecules with the acyl side chains of known T cell antigens,
      lipoarabinomannan, phosphatidylinositol mannoside, and glucose monomycolate.
      Furthermore, CD1b-antigen binding was optimal at acidic pH, consistent with the
      known requirement for endosomal acidification in CD1b-restricted antigen
      presentation. The mechanism for CD1b-ligand interaction involves the partial
      unfolding of the alpha helices of CD1b at acidic pH, revealing a hydrophobic
      binding site that could accommodate lipid. These data provide direct evidence
      that the CD1b molecule has evolved unique biochemical properties that enable the
      binding of lipid-containing antigens from intracellular pathogens.

PMID- 9529151
TI  - The tyrosine-containing cytoplasmic tail of CD1b is essential for its efficient
      presentation of bacterial lipid antigens.
AB  - CD1b is an antigen-presenting molecule that mediates recognition of bacterial
      lipid and glycolipid antigens by specific T cells. We demonstrate that the nine
      amino acid cytoplasmic tail of CD1b contains all of the signals required for its
      normal endosomal targeting, and that the single cytoplasmic tyrosine is a
      critical component of the targeting motif. Mutant forms of CD1b lacking the
      endosomal targeting motif are expressed at high levels on the cell surface but
      are unable to efficiently present lipid antigens acquired either exogenously or
      from live intracellular organisms. These results define the functional role of
      the CD1b targeting motif in a physiologic setting and demonstrate its importance
      in delivery of this antigen-presenting molecule to appropriate intracellular
      compartments.

PMID- 9529152
TI  - Coordinate regulation of complex T cell populations responding to bacterial
      infection.
AB  - Bacterial infections activate complex T cell populations that differ in size and
      antigen specificity. We used tetramerized MHC class I molecules complexed with
      Listeria monocytogenes-derived epitopes to characterize four distinct CD8+ T
      lymphocyte populations during bacterial infection. Surprisingly, T cell
      populations differing in antigen specificity expand, contract, and enter the T
      cell memory compartment synchronously. Because the four L. monocytogenes epitopes
      are presented with different efficiencies and have distinct stabilities in
      infected cells, our findings suggest that these factors do not determine in vivo
      T cell dynamics. While T cell activation requires antigen presentation, the
      timing and extent of T cell expansion appear to be regulated in a coordinated
      fashion independent of antigen quantity and stability.

PMID- 9529153
TI  - Humoral immunity due to long-lived plasma cells.
AB  - Conventional models suggest that long-term antibody responses are maintained by
      the continuous differentiation of memory B cells into antibody-secreting plasma
      cells. This is based on the notion that plasma cells are short-lived and need to
      be continually replenished by memory B cells. We examined the issue of plasma
      cell longevity by following the persistence of LCMV-specific antibody and plasma
      cell numbers after in vivo depletion of memory B cells and by adoptive transfer
      of virus-specific plasma cells into naive mice. The results show that a
      substantial fraction of plasma cells can survive and continue to secrete antibody
      for extended periods of time (>1 year) in the absence of any detectable memory B
      cells. This study documents the existence of long-lived plasma cells and
      demonstrates a new mechanism by which humoral immunity is maintained.

PMID- 9529154
TI  - Negative regulation of T cell homing by CD43.
AB  - We report that the cell surface mucin CD43 acts as an anti-adhesin on T
      lymphocytes. CD43-deficient murine lymphocytes homed significantly more
      frequently to secondary lymphoid organs than wild-type cells. Intravital
      microscopy of peripheral lymph node venules revealed that CD43-deficient
      lymphocytes were twice as likely to tether, roll, and stick than wild-type cells.
      This effect was due to CD43 interference with the homing receptor, L-selectin,
      and was most pronounced in venules with low L-selectin ligand density. In vitro,
      CD43-deficient cells tethered to L-selectin ligands more efficiently and rolled
      more slowly than wild-type lymphocytes. Thus, CD43 exerts a negative regulatory
      effect on T cell trafficking by counterbalancing L-selectin-mediated adhesion.

PMID- 9529155
TI  - Defective NK cell activity and Th1 response in IL-18-deficient mice.
AB  - IL-18 is a cytokine that is secreted from activated macrophages and induces
      IFNgamma production. To investigate the in vivo role of IL-18, we generated IL-18
      deficient mice. In Propionibacterium acnes (P. acnes)-primed IL-18-deficient
      mice, LPS-induced IFNgamma production was markedly reduced, despite normal IL-12
      induction. Natural killer cell activity was significantly impaired. Th1 cell
      response after injection of P. acnes or Mycobacterium bovis (bacillus Calmette
      Guerin [BCG]) was significantly reduced. Similar results were observed in IL-12
      deficient mice. Interestingly, Th1 response was induced after BCG infection in IL
      12-deficient mice. We therefore generated mice lacking both IL-18 and IL-12. In
      these mice, NK activity and Th1 response were further impaired. This demonstrates
      the important role of both IL-18 and IL-12 in NK activity, as well as in in vivo
      Th1 response.

PMID- 9529156
TI  - Role of cytoplasmic tail of the type 1A angiotensin II receptor in agonist- and
      phorbol ester-induced desensitization.
AB  - To investigate mechanisms underlying the agonist-induced desensitization of the
      type 1A angiotensin II receptor (AT1A-R), we have stably expressed in Chinese
      hamster ovary (CHO) cells the wild-type receptor and truncated mutants lacking
      varying lengths of the cytoplasmic tail. Assay of inositol 1,4,5-trisphosphate
      (IP3) formation in response to agonist demonstrated that the truncated mutants
      T318, T328, and T348 lacking the last 42, 32, or 12 amino acid residues,
      respectively, couple with Gq protein with an efficiency similar to that of full
      length receptors, whereas coupling of Gq protein was abolished in the T310
      truncated mutant devoid of the carboxyl-terminal 50 amino acids. Exposure of
      CHO/AT1A-R cells expressing the wild-type AT1A-R to angiotensin II resulted in
      rapid and dose-dependent homologous desensitization of receptor-mediated IP3
      formation, which was independent of the receptor internalization. Mastoparan, an
      activator of G protein-coupled receptor kinase (GRK), induced desensitization of
      the AT1A-R. The agonist-induced desensitization of the receptor was largely
      prevented by heparin, a potent inhibitor of GRK, whereas it was only partially
      attenuated by a protein kinase C (PKC)-specific inhibitor. The homologous or
      heterologous desensitization of the receptor was greatly impaired in the
      truncated mutants T318 and T328, lacking the Ser/Thr-rich (13 or 12 Ser/Thr
      residues) cytoplasmic tail of the AT1A-R. Deletion of the last two Ser residues,
      including one PKC consensus site in the receptor tail, prevented only phorbol 12
      myristate 13-acetate-induced desensitization by 30%. Moreover, we found an
      agonist-induced translocation of a heparin-sensitive kinase activity. The
      angiotensin II-stimulated heparin-sensitive kinase could phosphorylate a
      thioredoxin fusion protein containing the entire AT1A-R cytoplasmic tail (N295 to
      E359), which lacks consensus phosphorylation sites for GRK1, GRK2, and GRK3. The
      heparin-sensitive kinase may not be GRK2, GRK3, or GRK6 expressed in CHO/AT1A-R
      cells, since angiotensin II did not induce translocation of these receptor
      kinases. Potential Ser/Thr phosphorylation sites located between S328 and S347 in
      the cytoplasmic tail of AT1A-R seem to play a critical role in the heterologous
      and homologous desensitization of the receptor. A heparin-sensitive kinase other
      than GRK2, GRK3, or GRK6 may be involved in the agonist-induced homologous
      desensitization of the AT1A-R.

PMID- 9529157
TI  - Oscillatory shear stress stimulates adhesion molecule expression in cultured
      human endothelium.
AB  - Low and oscillatory shear stresses are major features of the hemodynamic
      environment of sites opposite arterial flow dividers that are predisposed to
      atherosclerosis. Atherosclerosis is a focal inflammatory disease characterized
      initially by the recruitment of mononuclear cells into the arterial wall. The
      specific characteristics of the hemodynamic environment that facilitate the
      generation of arterial inflammatory responses in the presence of, for example,
      hyperlipidemia are unknown. We show here that prolonged oscillatory shear stress
      induces expression of endothelial cell leukocyte adhesion molecules, which are
      centrally important in mediating leukocyte localization into the arterial wall.
      Vascular cell adhesion molecule-1 was upregulated an average 9-fold relative to
      endothelial monolayers in static culture. Intercellular adhesion molecule-1 and E
      selectin exhibited 11-fold and 7.5-fold increases, respectively. Upregulation of
      these adhesion molecules was associated with enhanced monocyte adherence.
      Cytokine stimulation of surface vascular cell adhesion molecule-1 was maximally
      induced after 6 and 8 hours of cytokine incubation. Oscillatory shear stress for
      these time periods elicited respective vascular cell adhesion molecule-1 levels
      of 16% and 30% relative to those observed for cytokine stimulation. Surface
      intercellular adhesion molecule-1 induction by cytokine stimulation for 24 hours
      was found to be approximately five times the level detected after 24 hours of
      oscillatory shear stress. Experiments performed in the presence of the
      antioxidant N-acetylcysteine demonstrated that the expression of vascular cell
      adhesion molecule-1 could be almost totally abolished, whereas that of
      intercellular adhesion molecule-1 was typically reduced by approximately 70%.
      These results imply that oscillatory shear stress per se is sufficient to
      stimulate mononuclear leukocyte adhesion and, presumptively, migration into the
      arterial wall. These results further indicate that atherosclerotic lesion
      initiation is likely related, at least in part, to unique signals generated by
      oscillatory shear stress and that the mechanism of upregulation is, to some
      extent, redox sensitive.

PMID- 9529158
TI  - Lactosylceramide stimulates human neutrophils to upregulate Mac-1, adhere to
      endothelium, and generate reactive oxygen metabolites in vitro.
AB  - Glycosphingolipids (GSLs) and their metabolites play important roles in a variety
      of biological processes. We have previously reported that lactosylceramide
      (LacCer), a ubiquitous GSL, stimulates NADPH oxidase-dependent superoxide
      generation by aortic smooth muscle cells and their consequent proliferation. We
      postulated that LacCer may upregulate adhesion molecules on human
      polymorphonuclear leukocytes (hPMNs), perhaps also via NADPH oxidase-dependent
      reactive oxygen metabolite (ROM) generation. Incubation of hPMNs with LacCer
      upregulated CD11b/CD18 (Mac-1) and CD11c/CD18, as determined by fluorescence
      automated cell sorting. LacCer also stimulated these hPMNs to generate superoxide
      via NADPH oxidase, as determined by lucigenin-enhanced chemiluminescence.
      However, the upregulation of Mac-1 by LacCer did not itself appear to be mediated
      by ROMs, since neither an antioxidant nor an NADPH oxidase inhibitor
      substantially inhibited the Mac-1 upregulation. However, this Mac-1 upregulation
      was significantly inhibited by two disparate phospholipase A2 (PLA2) inhibitors.
      Moreover, LacCer induced arachidonic acid metabolism, which was inhibited by the
      PLA2 inhibitors, but not by an NADPH oxidase inhibitor. To evaluate the effect of
      LacCer on hPMN adhesion to endothelium, hPMNs stimulated with LacCer were allowed
      to adhere to unstimulated human endothelial cell monolayers. LacCer stimulated
      hPMN adhesion to endothelial cells, which was blocked by anti-CD18 and by the
      PLA2 inhibitors. We conclude that LacCer stimulates both Mac-1 upregulation and
      superoxide generation in hPMNs but that ROMs are not the upstream signal for Mac
      1 upregulation. This mechanism may well be relevant to acute endothelial injury
      in inflammation and other pathological conditions.

PMID- 9529159
TI  - Inhibition of vascular smooth muscle cell growth by inhibition of fibronectin
      matrix assembly.
AB  - The regulation of vascular smooth muscle cell (VSMC) proliferation by the
      fibronectin matrix was tested by treating human umbilical artery smooth muscle
      cells (HUASMCs) with a recombinant fragment of fibronectin (protein III1-C) that
      has previously been shown to modulate fibronectin matrix assembly. III1-C
      inhibited HUASMC proliferation by 75% to 90%. The inhibition of growth was time
      dependent; III1-C had no effect on DNA synthesis after 0 to 5 hours of treatment
      but did have an effect at 24 hours and beyond. III1-C did not stimulate apoptosis
      in these cells, indicating that the inhibition of proliferation was not due to an
      induction of programmed cell death. The effects of III1-C on cell growth were
      only specific for normal diploid smooth muscle cells. III1-C had no effect on the
      proliferation of IMR-90 fibroblasts, endothelial cells, NIH 3T3 cells, or the rat
      aortic smooth muscle cell line A7r5. However, III1-C did inhibit proliferation by
      primary rat aortic smooth muscle cells. An analysis of HUASMC fibronectin
      receptor (integrin alpha5beta1) distribution revealed that III1-C did not inhibit
      alpha5beta1 localization to focal contacts. Moreover, III1-C had no effect on the
      relative expression levels of seven different integrin subunits on HUASMCs.
      However, III1-C did inhibit fibronectin matrix assembly by rat aortic smooth
      muscle cells, HUASMCs, A7r5 cells, IMR-90 cells, and endothelial cells. An
      analysis of fibronectin synthesis indicated that the inhibition of fibronectin
      matrix assembly by III1-C was not due solely to a decrease in fibronectin
      synthesis. Finally, treatment of HUASMCs with anti-fibronectin monoclonal
      antibody L8 (which is known to inhibit fibronectin matrix assembly) also
      decreased the rate of HUASMC DNA synthesis. These results demonstrate that III1-C
      inhibits VSMC proliferation and suggest that this effect may be mediated by the
      inhibition of fibronectin matrix assembly.

PMID- 9529161
TI  - Evolutionarily conserved promoter region containing CArG*-like elements is
      crucial for smooth muscle myosin heavy chain gene expression.
AB  - In recent years, significant progress has been made toward understanding skeletal
      muscle development. However, the mechanisms that regulate smooth muscle
      development and differentiation are presently unknown. To better understand
      smooth muscle-specific gene expression, we have focused our studies on the smooth
      muscle myosin heavy chain (SMHC) gene, a highly specific marker of differentiated
      smooth muscle cells. The goal of the present study was to isolate and
      characterize the mouse SMHC gene promoter, since the mouse promoter would be
      particularly suited for in vivo promoter analyses in transgenic mice and would
      serve as a tool for targeting genes of interest into smooth muscle cells. We
      report here the isolation and characterization of the mouse SMHC promoter and its
      5' flanking region. DNA sequence analysis of a 2.6-kb portion of the promoter
      identified several potential binding sites for known transcription factors.
      Transient transfection analysis of promoter deletion constructs in primary
      cultures of smooth muscle cells showed that the region between -1208 and -1050 bp
      is critical for maximal SMHC promoter activity. A comparison of SMHC promoter
      sequences from mouse, rat, and rabbit revealed the presence of a highly conserved
      region located between -967 and -1208 bp. This region includes three CArG/CArG*
      like elements, two SP-1 binding sites, a NF-1-like element, an Nkx2-5 binding
      site, and an Elk-1 binding site. Gel mobility shift assay and DNase I
      footprinting analyses show that all three CArG/CArG*-like elements can form DNA
      protein complexes with nuclear extract from vascular smooth muscle cells. Protein
      binding to the CArG* elements can be competed out by either serum response
      element or by an authentic CArG element from the cardiac alpha-actin gene. Using
      a serum response factor (SRF) antibody, we demonstrate that SRF is part of the
      protein complex. In addition, we show that cotransfection with the SRF dominant
      negative mutant expression vector abolishes SMHC promoter activity, suggesting
      that SRF protein plays a critical role in SMHC gene regulation.

PMID- 9529160
TI  - Modulation of Ca2+ channels by cyclic nucleotide cross activation of opposing
      protein kinases in rabbit portal vein.
AB  - Cyclic nucleotides are known to modify voltage-gated (L-type) Ca2+ channel
      activity in vascular smooth muscle cells, but the exact mechanism(s) underlying
      these effects is not well defined. The purpose of the present study was to
      investigate the modulatory role of the cAMP- and cGMP-dependent protein kinase
      (PKA and PKG, respectively) pathways in Ca2+ channel function by using both
      conventional and perforated-patch-clamp techniques in rabbit portal vein
      myocytes. The membrane-permeable cAMP derivative, 8-bromo cAMP (0.1 to 10
      micromol/L), significantly increased (14% to 16%) peak Ba2+ currents, whereas
      higher concentrations (0.05 to 0.1 mmol/L) decreased Ba2+ currents (23% to 31%).
      In contrast, 8-bromo cGMP inhibited Ba2+ currents at all concentrations tested
      (0.01 to 1 mmol/L). Basal Ca2+ channel currents were significantly inhibited by
      the PKA blocker 8-Bromo-2'-O-monobutyryladenosine-3',5'-monophosphorothioate, Rp
      isomer (Rp 8-Br-MP cAMPS, 30 micromol/L) and enhanced by the PKG inhibitor beta
      Phenyl-1,N2-etheno-8-bromoguanosine-3',5'-monophosphorothioate, Rp-isomer (Rp-8
      Br PET cGMPS, 10 nmol/L). In the presence of Rp 8-bromo PET cGMPS (10 to 100
      nmol/L), both 8-bromo cAMP (0.1 mmol/L) and 8-bromo cGMP (0.1 mmol/L) enhanced
      Ba2+ currents (13% to 39%). The excitatory effect of 8-bromo cGMP was blocked by
      Rp 8-bromo MB-cAMPS. Both 8-bromo cAMP (0.05 mmol/L) and forskolin (10
      micromol/L) elicited time-dependent effects, including an initial enhancement
      followed by suppression of Ba2+ currents. Ba2+ currents were also enhanced when
      cells were dialyzed with the catalytic subunit of PKA. This effect was reversed
      by the PKA blocker KT 5720 (200 nmol/L). Our results suggest that cAMP/PKA
      stimulation enhances and cGMP/PKG stimulation inhibits L-type Ca2+ channel
      activity in rabbit portal vein myocytes. Our results further suggest that both
      cAMP and cGMP have a primary action mediated by their own kinase as well as a
      secondary action mediated by the opposing kinase.

PMID- 9529162
TI  - Expression and regulation of adhesion molecules in cardiac cells by cytokines:
      response to acute hypoxia.
AB  - Adhesion molecules mediate inflammatory myocardial injury after
      ischemia/reperfusion. Cytokine release and hypoxia are features of acute ischemia
      that may influence expression of these molecules. Accordingly, we studied
      intercellular adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM)
      responses to cytokines and acute hypoxia in cultured myocardial cells. Northern
      blot analysis and immunoassay showed that the proinflammatory cytokines
      interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha stimulated
      concentration-dependent increases in ICAM and VCAM mRNA and protein. In both
      cardiac myocytes and fibroblasts, pretreatment with a specific inhibitor of
      nuclear transcription factor-kappaB (NF-kappaB) prevented cytokine induction of
      both molecules. We also found that inhibition of tyrosine kinase and p38/RK
      (stress-activated protein kinase) pathways prevented IL-1beta-induced ICAM and
      VCAM protein synthesis, whereas extracellular signal-regulated protein kinase
      (ERK1/ERK2) inhibition did not. Neither hypoxia (0% O2 for 6 hours) alone nor
      hypoxia/reoxygenation had any significant effect on ICAM and VCAM mRNA. However,
      hypoxia did enhance IL-1beta-induced ICAM mRNA expression in myocytes. As a
      possible mechanism of this synergistic action on CAM expression, hypoxia induced
      a time-dependent increase in the DNA binding activity of both NF-kappaB and
      activator protein-1 (AP-1), two transcription factors important for cell adhesion
      molecule expression. In contrast to the enhanced ICAM mRNA induced by IL-1beta
      during hypoxia, however, protein levels for this adhesion molecule were unchanged
      beyond IL-1beta-stimulated levels, suggesting posttranscriptional and/or
      posttranslational control mechanisms. We conclude that cytokines regulate ICAM
      and VCAM mRNA and protein in both cardiac myocytes and fibroblasts. Furthermore,
      adhesion molecule induction requires translocation of at least two transcription
      factors, NF-kappaB and AP-1.

PMID- 9529163
TI  - Early coronary angiogenesis in response to thyroxine: growth characteristics and
      upregulation of basic fibroblast growth factor.
AB  - Although a substantial coronary angiogenesis occurs after thyroid hormone
      treatment, its regulation and relationship to cardiac hypertrophy are not
      understood. This study was designed to determine (1) the onset of capillary
      proliferation, (2) the sites of capillary proliferation, and (3) whether basic
      fibroblast growth factor (bFGF) upregulation occurs in response to thyroxine
      administration. Male Sprague-Dawley rats were injected daily with L-thyroxine
      (T4, 0.2 mg/kg s.c.). Bromodeoxyuridine labeling of capillary endothelial cells
      increased during the first 24 hours of treatment and peaked after 2 days of
      treatment. Northern blot analysis revealed a slight increase in bFGF mRNA during
      this period, followed by a doubling of expression by 48 hours, at which time bFGF
      protein was also increased. In situ hybridization, used to localize bFGF mRNA,
      showed an increase in transcripts within 24 hours after T4. This enhancement was
      uniform in the epimyocardium and endomyocardium. Histochemical analysis (double
      staining for alkaline phosphatase and dipeptidyl peptidase) of frozen sections,
      used to discriminate capillary profiles as arteriolar and venular, respectively,
      showed that growth occurred in the latter, since the percentage of capillary
      profiles positive for dipeptidyl peptidase was higher than the control value
      after 4 days of T4 administration. These data indicate that in the thyroxine
      model of cardiac hypertrophy (1) capillary DNA synthesis occurs after a single
      injection of thyroxine, (2) capillary growth coincides with an upregulation in
      bFGF mRNA and increase in bFGF protein, and (3) proliferation occurs in the
      venular capillaries.

PMID- 9529164
TI  - Effects of constitutive overexpression of insulin-like growth factor-1 on the
      mechanical characteristics and molecular properties of ventricular myocytes.
AB  - Recently, insulin-like growth factor-1 (IGF-1) has been claimed to positively
      influence the cardiac performance of the decompensated heart. On this basis, the
      effects of constitutive overexpression of IGF-1 on the mechanical behavior of
      myocytes were examined in transgenic mice in which the cDNA for the human IGF-1B
      was placed under the control of a rat alpha-myosin heavy chain promoter. In mice
      heterozygous for the transgene and in nontransgenic littermates at 2.5 months of
      age, the alterations in Ca2+ sensitivity of tension development, unloaded
      shortening velocity, and sarcomere compliance were measured in skinned myocytes.
      The quantities and state of phosphorylation of myofilament proteins in these
      enzymatically dissociated ventricular myocytes were also examined. The
      overexpression of IGF-1 was characterized by a nearly 15% reduction in
      myofilament isometric tension at submaximum Ca2+ levels in the physiological
      range, whereas developed tension at maximum activation was unchanged. In
      contrast, unloaded velocity of shortening was increased 39% in myocytes from
      transgenic mice. Moreover, resting tension in these cells was reduced by 24% to
      33%. Myocytes from nontransgenic mice pretreated with IGF-1 failed to reveal
      changes in myofilament Ca2+ sensitivity and unloaded velocity of shortening. The
      quantities of C protein, troponin I, and myosin light chain-2 were comparable in
      transgenic and nontransgenic mice, but their endogenous state of phosphorylation
      increased 117%, 100%, and 100%, respectively. Troponin T content was not altered,
      and myosin isozymes were essentially 100% V1 in both groups of mice. In
      conclusion, constitutive overexpression of IGF-1 may influence positively the
      performance of myocytes by enhancing shortening velocity and cellular compliance.

PMID- 9529165
TI  - Differential expression of gap junction proteins in the canine sinus node.
AB  - Electrical coupling of pacemaker cells at gap junctions appears to play an
      important role in sinus node function. Although the major cardiac gap junction
      protein, connexin43 (Cx43), is expressed abundantly in atrial and ventricular
      muscle, its expression in the sinus node has been a subject of controversy. The
      objectives of the present study were to determine whether Cx43 is expressed by
      sinus node myocytes, to characterize the spectrum of connexin expression
      phenotypes in sinus node pacemaker cells, and to define the spatial distribution
      of different connexin phenotypes in the intact sinus node. To fulfill these
      objectives, we performed high-resolution immunohistochemical analysis of
      disaggregated adult canine sinus node preparations. Using enhanced tissue
      preservation and antigen retrieval techniques, we also performed
      immunohistochemical studies on sections of intact canine sinus node tissue.
      Analysis of disaggregated sinus node preparations revealed three populations of
      pacemaker cells distinguished on the basis of connexin immunohistochemical
      phenotype: approximately 55% of cells expressed only connexin40 (Cx40); 30% to
      35% of cells expressed Cx43, connexin45 (Cx45), and Cx40; and the remaining cells
      had no detectable connexin expression. In immunostained sections of intact sinus
      node, Cx43- and Cx45-positive cells were limited in their distribution and were
      observed in discrete bundles that appeared to abut atrial myocytes. In contrast,
      Cx40 immunoreactive signal was widely distributed in the sinus node region. These
      results indicate that subsets of pacemaker cells express distinct connexin
      phenotypes. Differential expression of connexins could create regions within the
      sinus node with different conduction properties, thereby contributing to the
      nonuniform conduction properties seen in this tissue.

PMID- 9529166
TI  - Effects of in vivo administration of anti-B7-1/B7-2 monoclonal antibodies on
      murine acute myocarditis caused by coxsackievirus B3.
AB  - In viral myocarditis, we previously reported that antigen-specific T cells
      infiltrate the heart and play an important role in the pathogenesis of myocardial
      damage. For antigen-specific T-cell activation to occur, it is necessary for T
      cells to receive costimulatory signals provided by costimulatory molecules
      expressed on antigen-presenting cells as well as main signals provided by binding
      of T-cell receptors to antigens. To investigate the roles of costimulatory
      molecules B7-1 and B7-2 in the development of acute viral myocarditis, we first
      analyzed the expression of B7-1/B7-2 in the hearts of mice with acute viral
      myocarditis induced by coxsackievirus B3 (CVB3). Second, we evaluated the
      induction of B7-1/B7-2 in cultured cardiac myocytes treated with interferon gamma
      (IFN-gamma). Third, we examined the effects of in vivo administration of anti-B7
      1/B7-2 monoclonal antibodies (mAbs) on the development of acute viral
      myocarditis. We found that CVB3-induced murine acute myocarditis resulted in
      enhanced expression of B7-1/B7-2 in cardiac myocytes. The expression of B7-1/B7-2
      in cardiac myocytes could be induced in vitro by IFN-gamma. We found that in vivo
      anti-B7-1 mAb treatment markedly decreased myocardial inflammation, whereas anti
      B7-2 mAb treatment abrogated the protective effect of anti-B7-1. Our findings
      indicate that distinct roles for B7-1 and B7-2 antigens are involved in the
      development of acute viral myocarditis and raise the possibility of immunotherapy
      with anti-B7-1 mAb to prevent T-cell-mediated myocardial damage in viral
      myocarditis.

PMID- 9529167
TI  - Angiotensin II potentiates vascular endothelial growth factor-induced angiogenic
      activity in retinal microcapillary endothelial cells.
AB  - Angiotensin II (Ang II) plays a role in the development of many vascular
      diseases. In the present study, we have investigated the effect of Ang II on
      vascular endothelial growth factor (VEGF) receptor expression and VEGF-induced
      angiogenic activity in bovine retinal microcapillary endothelial cells (BRECs).
      Ang II induced a significant increase of kinase domain-containing receptor/total
      liver kinase (KDR/Flk-1) mRNA in a time- and dose-dependent manner, with a
      maximal 4.3+/-0.8-fold increase after a 4-hour stimulation. Ang II increased the
      rate of KDR gene transcription by 5.4-fold, whereas the half-life of KDR mRNA was
      not increased significantly. The increase depended partially on new protein
      synthesis. The Ang II-induced KDR mRNA increase was inhibited by either
      [Sar1,Ile8]angiotensin or angiotensin type 1 receptor antagonists but was not
      significantly altered by angiotensin type 2 receptor antagonists. The PKC
      inhibitor reduced Ang II-induced KDR mRNA expression by 70+/-15%. The tyrosine
      kinase inhibitor reduced the Ang II- and phorbol 12-myristate 13-acetate-induced
      KDR mRNA increases by 35+/-8% and 44+/-26%, respectively. Ang II increased by 3.1
      fold the 35S-labeled KDR/Flk-1 immunoprecipitated by a specific antibody to
      KDR/Flk-1. Scatchard analysis demonstrated that Ang II induced a significant
      increase of binding sites without changing binding affinity. Ang II enhanced VEGF
      induced cell growth and tube formation. Ang II itself had no effect on cell
      growth, tube formation, or mRNA levels of VEGF and tms-like tyrosine kinase (Flt
      1) in BRECs. These findings suggest that Ang II might potentiate VEGF-induced
      angiogenic activity through an increase of the VEGF receptor KDR/Flk-1.

PMID- 9529168
TI  - Central and regional hemodynamics during crystalloid fluid therapy after
      uncontrolled intra-abdominal bleeding.
AB  - OBJECTIVE: To study the effect of graded crystalloid fluid resuscitation on
      central hemodynamics and outcome after intra-abdominal hemorrhage. METHODS: Ten
      minutes after a 5-mm long laceration was produced in the infrarenal aorta, 32
      pigs were randomized to receive either no fluid or Ringer's solution in the
      proportion 1:1, 2:1, or 3:1 to the expected amount of blood lost per hour (26 mL
      kg[-1]) over 2 hours. The hemodynamics were studied using arterial and pulmonary
      artery catheters and four blood flow probes placed over major blood vessels.
      RESULTS: During the first 40 minutes after the injury, the respective blood flow
      rates in the distal aorta were 39% (no fluid), 41% (1:1), 56% (2:1), and 56%
      (3:1) of the baseline flow. Fluid resuscitation increased cardiac output but had
      no effect on arterial pressure, oxygen consumption, pH, or base excess.
      Rebleeding occurred only with the 2:1 and 3:1 fluid programs. Survival was
      highest with the 1:1 and 2:1 programs. CONCLUSIONS: Crystalloid fluid therapy
      improved the hemodynamic status but increased the risk of rebleeding. Therefore,
      a moderate fluid program offered the best chance of survival.

PMID- 9529169
TI  - Effects of abdominal decompression on cardiopulmonary function and visceral
      perfusion in patients with intra-abdominal hypertension.
AB  - OBJECTIVE: Increased intra-abdominal pressure (IAP) compromises cardiopulmonary
      function and visceral perfusion. Our goal was to characterize acute changes in
      these subsystems associated with operative abdominal decompression. PATIENT
      POPULATION: A series of 11 consecutive injured patients monitored with a
      pulmonary artery catheter and nasogastric tonometer in whom operative
      decompression was performed. Indications for decompression included oliguria or
      progressive acidosis despite aggressive resuscitation in the presence of elevated
      IAP (>25 mm Hg). MAIN OUTCOME MEASURES: Studied hemodynamic variables included
      pulmonary artery occlusion pressure (PAOP), right ventricular end-diastolic
      volume index (RVEDVI), and cardiac index (CI). Pulmonary variables included shunt
      fraction (Qs/Qt) and dynamic compliance (Cdyn). Visceral perfusion was assessed
      using hourly urine output 4 hours before and after decompression (UOP) and
      gastric intramucosal pH (pHi). Mean values before and after decompression were
      compared using the paired t test. Linear regression and Fisher's z transformation
      were used to evaluate the relationships between RVEDVI, PAOP, CI, and IAP. IAP
      was transduced via bladder pressures. Significance was defined as p < 0.05. Data
      are expressed as means+/-SD. RESULTS: IAP decreased with decompression (49+/-11
      to 19+/-6.8 mm Hg; p < 0.0001). RVEDVI improved independent of CI and correlated
      better (p < 0.01) with CI (r =0.49, p=0.04) than PAOP did (r=-0.36, p=0.09). PAOP
      correlated significantly with IAP (r=0.45, p=0.04). Decompression resulted in
      significant improvements in Qs/Qt, Cdyn, UOP, and pHi. CONCLUSION: Abdominal
      decompression in patients with increased IAP improves preload, pulmonary
      function, and visceral perfusion. Elevated IAP has important effects on PAOP,
      which makes the PAOP an unreliable index of preload in these patients.

PMID- 9529170
TI  - Effects of intra-abdominal hypertension on hepatic energy metabolism in a rabbit
      model.
AB  - BACKGROUND: Intra-abdominal hypertension is known to decrease hepatic blood flow,
      but its effect on hepatic energy level has not described. METHODS: Fifty-three
      rabbits were mechanically ventilated and divided into five groups. Intra
      abdominal hypertension was induced by saline infusion and maintained for 30
      minutes. Hepatic sinusoidal functional blood flow was evaluated by means of
      indocyanine green disappearance rate (ICG-K), hepatic mitochondrial redox status
      was evaluated by arterial ketone body ratio, and tissue energy level was
      evaluated by energy charge (EC). RESULTS: At an intra-abdominal pressure of 20 mm
      Hg, ICG-K was significantly decreased, with no decrease in EC. At 30 mm Hg,
      hypoxemia developed and the ICG-K decreased further, with significant decreases
      observed in arterial ketone body ratio and EC. The latter were not increased by
      administration of oxygen. CONCLUSION: At an intra-abdominal pressure of 20 mm Hg,
      a slight decrease in sinusoidal flow did not affect hepatic energy level. At 30
      mm Hg, a reduced hepatic mitochondrial redox status and a decreased energy level
      were attributed to a decrease in sinusoidal flow in this animal model.

PMID- 9529171
TI  - Pressure-volume characteristics of the intact and disrupted pelvic
      retroperitoneum.
AB  - Hemorrhage is a major cause of mortality in pelvic fractures. Bleeding can be
      controlled in hypotensive patients by direct ligation, angiographic embolization,
      pelvic packing, and acute external fixation. Acute application of an external
      fixator can reduce pelvic volume and reduce bleeding fractures to effect
      tamponade. This therapy assumes that the pelvis represents a closed space, which
      clearly is not true anatomically. However, the premise may hold functionally.
      This study explored the relationship between pressure and volume in the intact
      and disrupted pelvic retroperitoneum. In cadaveric specimens, the external iliac
      vein was dissected, ruptured, and cannulated. This method allowed controlled flow
      of fluid, with simultaneous measurement of pressure, into the intact
      retroperitoneum. Open book pelvic fractures were created by applying external
      rotation to the pelvis through the femoral heads. The pressure-volume
      measurements, without and with external fixation applied, were repeated after the
      fracture, as well as after a laparotomy. In the intact retroperitoneum, pressures
      rapidly rose to an average of 30 mm Hg after infusion of 5 liters of fluid. After
      fracture, up to 20 liters of fluid could be infused at pressures not exceeding 35
      mm Hg. External fixation increased pressures approximately 3 mm Hg at low fluid
      volumes, and approximately 11 mm Hg at the highest fluid volumes. Laparotomy
      decreased retroperitoneal pressure from approximately 35 mm Hg to approximately
      15 mm Hg. The results of the study suggest that low-pressure venous hemorrhage
      may be tamponaded by an external fixator, given that enough fluid volume is
      present in the pelvic retroperitoneum. However, external fixation may not
      generate sufficient pressure to stop arterial bleeding. In any case, it seems
      that a large volume of fluid must be lost into the pelvis before an external
      fixator can have much effect on retroperitoneal pressures.

PMID- 9529173
TI  - Burn wound infection-induced myeloid suppression: the role of prostaglandin E2,
      elevated adenylate cyclase, and cyclic adenosine monophosphate.
AB  - Suppressed granulocyte and macrophage growth after burn infection or
      endotoxicosis appears to be mediated by macrophage-derived products. In this
      study, we found that after burn, burn plus infection, or endotoxicosis,
      peritoneal-elicited macrophages or bone marrow cells released increased amounts
      of prostaglandin E2 (PGE2) and inhibited growth of granulocyte-macrophage
      progenitor cells (GM-CFC). PGE2, when added in culture, inhibited in vitro GM-CFC
      growth in a dose-dependent manner. Pretreatment of bone marrow cells with either
      dibutyryl cyclic adenosine monophosphate or Forskolin in vitro mimicked the PGE2
      inhibition, further aggravated the inhibition induced by burn, burn plus
      infection, or endotoxicosis, and was not blocked by co-culture with indomethacin.
      Pretreatment of bone marrow cells with SQ22536, an adenylate cyclase inhibitor,
      significantly restored the suppressed GM-CFC growth found after burn, burn plus
      infection, or endotoxicosis. Alterations in myeloid production after burn
      infection appear to be related in part to the level of intracellular cyclic
      adenosine monophosphate for the GM-CFC and are responsive to PGE2.

PMID- 9529172
TI  - Effects of trauma and sepsis on soluble L-selectin and cell surface expression of
      L-selectin and CD11b.
AB  - OBJECTIVES: To examine (1) the effects of trauma on changes in neutrophil L
      selectin and CD11b expression and on the levels of soluble L-selectin and (2)
      whether these alterations are different on leukocyte subpopulations in those
      patients who develop multiple organ dysfunction syndrome. MATERIALS AND METHODS:
      Twenty patients with Injury Severity Score (ISS) > or = 16 and 15 patients with
      ISS score < 16 were studied. Arterial blood were collected serially after injury.
      The staining of leukocyte surface adhesion molecules was performed with
      antibodies against L-selectin and CD11b. Positive cell count and mean
      fluorescence intensity were determined by flow cytometry. Soluble L-selectin was
      measured using enzyme-linked immunosorbent assay. RESULTS: In patients with ISS >
      or = 16, neutrophil L-selectin expression showed an immediate increase, reaching
      peak levels between 3 to 4 hours after injury (p < 0.05 vs. patients with ISS <
      16), followed by a gradual decrease. Plasma levels of soluble L-selectin reached
      peak levels at 6 hours after injury. However, in patients with ISS < 16, minimal
      changes in L-selectin expression and soluble L-selectin were observed. Neutrophil
      CD11b expression showed an immediate increase for the first 3 hours followed by a
      gradual increase up to 24 hours after injury. In patients who developed multiple
      organ dysfunction syndrome, CD11b both on neutrophils and lymphocytes remained
      elevated for 120 hours. CONCLUSIONS: These findings suggest that acute neutrophil
      activation is an early event after trauma and may be implicated as "a vulnerable
      window" for leukocyte-mediated end organ injury.

PMID- 9529174
TI  - Immunosuppressants decrease neutrophil chemoattractant and attenuate
      ischemia/reperfusion injury of the liver in rats.
AB  - BACKGROUND: Neutrophils may play an important role in the development of liver
      ischemia/reperfusion injury. We investigated the effects of the
      immunosuppressants azathioprine (AZA), cyclosporine A (CsA), tacrolimus (FK506),
      and rapamycin (RPM) on the expression of cytokine-induced neutrophil
      chemoattractant (CINC) after ischemia/reperfusion of the liver. METHODS: Liver
      ischemia was induced in male Wistar rats by occluding the portal vein with a
      microvascular clip for 30 minutes. Rats received two intramuscular injections of
      AZA (4 mg/kg), CsA (5 mg/kg), FK506 (0.5 mg/kg), or RPM (0.5 mg/kg) 3 and 24
      hours before ischemia/reperfusion of the liver. RESULTS: Serum CINC
      concentrations in untreated animals increased, peaked 6 hours after reperfusion,
      and thereafter decreased gradually. Pretreatment with AZA, CsA, FK506, and RPM,
      however, inhibited the increase in serum CINC concentrations after reperfusion.
      CINC mRNA in liver tissue increased and peaked 3 hours after reperfusion, but was
      significantly lower in animals treated with AZA, CsA, FK506, and RPM. In vitro
      CINC production by Kupffer cells harvested from animals treated with AZA, CsA,
      FK506, or RPM 3 hours after reperfusion was also significantly lower than that
      observed in untreated animals. Both myeloperoxidase activity and the number of
      neutrophils accumulating in the liver 24 hours after reperfusion in animals
      treated with AZA, CsA, FK506, and RPM were significantly lower than in untreated
      animals. This correlated with lower serum aspartate transaminase, alanine
      transaminase, and lactate dehydrogenase levels in animals treated with AZA, CsA,
      FK506, and RPM 24 hours after reperfusion. CONCLUSION: The immunosuppressants
      AZA, CsA, FK506, and RPM reduce neutrophil accumulation and attenuate
      ischemia/reperfusion injury of the liver.

PMID- 9529175
TI  - Hypothermia, but not 100% oxygen breathing, prolongs survival time during lethal
      uncontrolled hemorrhagic shock in rats.
AB  - OBJECTIVE: To test the hypothesis that moderate hypothermia (Hth) (30 degrees C)
      or breathing 100% oxygen (best with both combined) would prolong survival during
      lethal uncontrolled hemorrhagic shock (UHS) compared with normothermia (38
      degrees C) and breathing air. METHODS: Forty Sprague-Dawley rats were
      anesthetized with halothane during spontaneous breathing of N2O/O2 (50:50). UHS
      was induced by volume-controlled blood withdrawal of 3 mL/100 g over 15 minutes,
      followed by 75% tail amputation and randomization to one of four UHS treatment
      groups (10 rats each): group 1 (control) was maintained on room air and rectal
      temperature of 38 degrees C; group 2 (Hth) was maintained on air and 30 degrees
      C; group 3 (O2) was maintained on FiO2 100% (starting immediately after tail cut)
      and 38 degrees C; and group 4 (O2-Hth) was maintained on FiO2 100% and 30 degrees
      C. Rats were observed otherwise untreated until death (apnea and pulselessness)
      or for a maximum of 5 hours. RESULTS: During the initial blood withdrawal, mean
      arterial pressure (MAP) decreased to an average of 24 mm Hg. Seventeen of 40 rats
      then showed an increase in MAP (attempted self-resuscitation). Induction of
      hypothermia increased MAP to around 35 mm Hg at 30 minutes but did not increase
      bleeding. Additional blood loss from the tail stump averaged 1.0, 2.3, 2.9, and
      1.7 mL in groups 1, 2, 3, and 4, respectively (not significant). Breathing 100%
      oxygen did not affect MAP or blood loss. Survival time was a mean of 47 and 52
      minutes in normothermic groups 1 and 3 versus 121 and 135 minutes in hypothermic
      groups 2 and 4, respectively (p < 0.001, Kaplan-Meier). Breathing FiO2 100%
      increased PaO2 but did not change MAP, blood loss, or survival time. CONCLUSION:
      Moderate hypothermia, but not increased FiO2, prolonged survival time during
      untreated UHS in rats. The effect of hypothermia on survival after resuscitation
      from UHS needs to be determined.

PMID- 9529176
TI  - Penetrating trauma to the male external genitalia.
AB  - BACKGROUND: We report on 40 patients with penetrating trauma to the external
      genitalia. Initial evaluation and management, operative findings, and treatment
      outcomes are reviewed. METHODS: We retrospectively reviewed the medical records
      of all patients presenting to our facility with penetrating trauma to the
      external genitalia since 1988. RESULTS: Of the 40 patients reviewed, 22 sustained
      isolated scrotal trauma, 10 sustained isolated penile trauma, and 8 had both
      scrotal and penile injuries. Twenty-nine of the 30 men with scrotal injuries
      underwent surgical exploration, and 21 of these were found to have injuries to
      the spermatic cord or testes (in 2 patients, bilateral injuries were noted). The
      testicular salvage rate was 35%. Penile trauma occurred in 18 patients. Eight
      corporal injuries and four urethral injuries were managed with debridement and
      primary repair. Erection and normal voiding was present in all men undergoing
      reconstruction who returned for follow-up. Thirty-eight percent of tested
      patients were positive for hepatitis B, C, or both. More than 60% of tested
      patients were legally intoxicated at the time of injury. Injuries separate from
      genitourinary trauma were identified in 72% of the men. CONCLUSION: Early
      surgical exploration with conservative debridement and primary repair of injured
      structures is recommended for most men who sustain penetrating injuries to the
      external genitalia. Selected patients with superficial injuries can be managed
      nonoperatively, but delayed wound complications are not uncommon. Although
      universal precautions are recommended for all patients, the high prevalence of
      hepatitis B and C in this group reemphasizes their importance. Long-term follow
      up in this largely young, mobile, indigent population was poor.

PMID- 9529177
TI  - Cerebral hemodynamic response to CO2 after severe head injury: clinical and
      prognostic implications.
AB  - OBJECTIVE: To study the cerebrovascular reactivity to CO2 after severe head
      injury to establish the clinical and prognostic relevance of CO2 reactivity.
      METHODS: Cerebrovascular reactivity to CO2 was studied in 20 patients with severe
      head injuries at 3.0+/-1.8 days after trauma onset. Two cerebral blood flow
      studies were performed to measure CO2 reactivity: the first study in a condition
      of normocapnia and the second study in a condition of relative hypocapnia.
      RESULTS: Global reactivity was superimposable to that found in awake, normocapnic
      subjects and did not correlate with age and Glasgow Coma Scale score but was
      dependent on the type of brain lesion. Moreover, reactivity correlated with
      outcome in patients studied after the first 3 days after trauma. CONCLUSIONS: Our
      data suggest that cerebrovascular reactivity is (a) almost preserved after a
      severe head injury; (b) significantly influenced by type of brain lesion; (c)
      prognostically relevant only in patients studied after the first 3 days after
      trauma.

PMID- 9529178
TI  - Is cervical spine imaging indicated in gunshot wounds to the cranium?
AB  - BACKGROUND, MATERIALS AND METHODS: Because there is no consensus regarding the
      necessity of imaging the cervical spine of patients who sustain a gunshot wound
      to the cranium, the cervical spinal radiographs of 53 consecutive patients with
      gunshot wounds to the cranium admitted to Hermann Hospital, a Level I trauma
      center, from January of 1993 to January of 1996, were reviewed. RESULTS: The
      cervical spine radiographs of all 53 patients were negative. CONCLUSIONS:
      Cervical spine injury is not associated with gunshot wound to the cranium.
      Therefore, patient management decisions/procedures, including endotracheal
      intubation, should not be delayed pending cervical spine imaging.

PMID- 9529179
TI  - Minimally displaced distal radius fractures: do they need plaster treatment?
AB  - In a prospective, randomized trial, minimally displaced distal radius fractures
      were divided into two groups: those treated with plaster immobilization for 1
      week compared with 3 weeks. Functional Cooney scores were determined at 6 weeks,
      3 months, 6 months, and 1 year. No statistical differences could be found in
      functional outcome between the groups at any time during the evaluation. Although
      patients did not allow immediate functional treatment in the presence of a
      fracture, we could not find any differences between 1 week or 3 weeks of plaster
      treatment. No further dislocation occurred, and all patients experienced eventful
      healing with good and excellent results in 92% of the cases. We believe,
      therefore, that only minimal immobilization is required in these fractures and
      that they should be mobilized as soon as comfort allows.

PMID- 9529180
TI  - Epidemiology of childhood injury.
AB  - A review of childhood injuries at the Wesley Guild Hospital, a component of
      Obafemi Awolowo University Teaching Hospital Complex, Ile-Ife, Nigeria, showed
      that 1,471 patients seen in the children's emergency room during a period of 4
      years (1992-1995) were there as a result of trauma, representing 9% of all
      patients seen. The case notes and accident and emergency cards of 1,224 were
      available for review. Ages ranged from 2 months to 15 years, with a mean of 6.9
      years, and 40% of the patients were between 5 and 10 years of age. More males
      were affected than females, with a ratio of 1.5:1. Road traffic crashes were the
      most common causal factor, responsible for 324 injuries (26.5%). About 90% of
      these were pedestrians knocked down by automobiles and motorcycles. Passengers
      accounted for about 10% of the cases. Falls occurred in 305 patients (25%); 229
      patients fell while on level ground either playing or running, accounting for
      75%. There were 122 patients (10%) with misplaced foreign bodies; about 60% of
      these were recovered from the ears, and 26.3% from the nostrils. Edible seeds
      were the most common foreign bodies, followed by beads. Injuries from bites
      occurred in 108 patients, with dog and snake bites taking the lead. Burns, mainly
      from scalding, occurred in 89 patients. Other rare injuries were knife wounds,
      gunshot wounds, and injuries resulting from assaults. The home was the most
      common site of injury (570 patients, 46.7%) followed by streets or roadways (363
      patients, 29.7%); 19.5% of injuries occurred at school. The most common anatomic
      region affected was the head and neck, followed by the limbs. One hundred ninety
      seven patients (16%) had bony fractures, femurs being the most affected bone.
      Head injury was seen in 104 patients, representing 8.5%, although only 17 of
      these injuries were severe. There were 10 cases of abdominal injury and 9 cases
      of chest injury, representing 0.8 and 0.7%, respectively. Wound infection
      occurred in 6.4% of the patients. Death occurred in 19 patients, accounting for
      1.6%; 10 of these patients had severe head injuries. Road traffic injuries and
      burns accounted for the greatest number of complications. The findings of this
      study suggest that trauma is an important factor in childhood morbidity and
      mortality in our environment, with road traffic injuries taking the lead.
      Preschool pedestrian children were most commonly affected, the majority of them
      on errands for their parents. We believe that the majority of these injuries are
      preventable.

PMID- 9529181
TI  - Cognitive knowledge decline after Advanced Trauma Life Support courses.
AB  - OBJECTIVE: To assess the cognitive knowledge decline among graduates of the
      Advanced Trauma Life Support (ATLS) program in Israel, to compare the rate of
      decline between surgeons and nonsurgeons, and to recommend appropriate timing for
      refresher courses. METHODS: A prospective study based on multiple-choice question
      test results of 220 ATLS course graduates was conducted 3 to 60 months after
      course completion. These results were then compared with the examination results
      immediately after the course. A statistical model based on survival analysis was
      used to evaluate the decline pattern and extent and to compare the study groups.
      RESULTS: A significant decline of cognitive knowledge over time among ATLS
      graduates was demonstrated. This decline was significantly greater in the
      nonsurgical group. A critical point of 20% cognitive knowledge loss among 50% of
      the examined physicians was observed around the 180th week after completion of
      the course. CONCLUSION: Physicians taking the ATLS course lose a significant part
      of their acquired cognitive knowledge after 3.5 years. Surgeons retain their
      cognitive knowledge for longer periods of time. Based on the study results, the
      optimal timing for a refresher course is between 3 and 4 years after the initial
      ATLS course.

PMID- 9529182
TI  - Growth hormone improves the resistance of thermally injured mice infected with
      herpes simplex virus type 1.
AB  - BACKGROUND: Growth hormone (GH) has been shown to promote wound healing and to
      improve protein metabolism in burned patients. Through immunomodulation, GH has
      also protected rats infected with Salmonella typhimurium and mice infected with
      Escherichia coli. In spite of advances in the management of patient care for
      those with thermal injuries, high mortality rates of burned patients as a result
      of infections are of special concern. An improvement in the resistance of burned
      patients to certain infections will make the beneficial role of GH very clear. In
      this study, therefore, the immunomodulating effects of recombinant human GH
      (rhGH) in thermally injured mice exposed to opportunistic herpesvirus infections
      were investigated. METHODS: (1) Burned mice, exposed to herpes simplex virus type
      1 (HSV-1), were treated subcutaneously with rhGH (4 mg/kg) and observed for 21
      days to determine the protective antiviral effect of rhGH. (2) Because of reports
      describing a lack of interferon-gamma (IFN-gamma) responsiveness in burned mice,
      the IFN-gamma-producing ability of the splenic mononuclear cells (SMNC) from
      burned mice treated with rhGH was examined. (3) Because the generation of burn
      associated suppressor macrophages that can inhibit the IFN-gamma production by
      SMNC has been previously described, the suppressor cell activities of macrophages
      from burned mice treated with rhGH were examined. RESULTS: After exposure to
      lethal amounts of HSV-1, mice treated with rhGH displayed a reduced mortality
      rate compared with control mice treated with saline. SMNC from burned mice
      treated with rhGH produced IFN-gamma, whereas this cytokine was not produced by
      SMNC from burned mice treated with saline. Also, an inhibition of the generation
      of burn-associated suppressor macrophages was displayed in burned mice treated
      with rhGH. CONCLUSION: Exogenous administration of rhGH caused an improvement in
      the resistance of burned mice to HSV-1 infection. In burned mice treated with
      rhGH, the impaired IFN-gamma responsiveness was restored and the generation of
      burn-associated suppressor macrophages was inhibited. IFN-gamma, a typical
      antiviral cytokine induced by rhGH through the regulation of the suppressor
      macrophage generation, may therefore play a role in the protection of burned mice
      infected with a lethal amount of HSV-1.

PMID- 9529183
TI  - Cutaneous burns caused by sulfuric acid drain cleaner.
AB  - BACKGROUND: Highly concentrated solutions of sulfuric acid are available to
      unclog drains. We have noted a substantial number of both accidental and
      intentional cutaneous burns caused by these agents. METHODS: A retrospective
      review was conducted of children and adults who sustained sulfuric acid burns
      over a 13-year period ending in May 1996. Reports of injuries related to drain
      cleaners filed with the United States Consumer Product Safety Commission between
      1991 and 1995 were also reviewed. RESULTS: Twenty-one patients (13 children, 8
      adults) sustained cutaneous burns caused by concentrated sulfuric acid solutions.
      In 8 instances, the burn was accidental, whereas in 13 cases, sulfuric acid was
      used as a weapon. Median total body surface area burned was 5% (range, 1-25%).
      Approximately 50% of burns involved the face and neck. Skin grafting was required
      in 14 patients (66%). It is estimated that nationwide approximately 3,000
      injuries per year are related to drain cleaners and that one-third of these
      involve cutaneous burns. CONCLUSION: Highly concentrated sulfuric acid drain
      cleaner can produce full-thickness cutaneous burns that require skin grafting in
      the majority of cases. Proper use of these agents and sequestering them from
      children may reduce accidental contact; however, their abuse as agents of assault
      remains a source of significant morbidity.

PMID- 9529184
TI  - A prospective study of omeprazole suspension to prevent clinically significant
      gastrointestinal bleeding from stress ulcers in mechanically ventilated trauma
      patients.
AB  - OBJECTIVE: To prospectively evaluate the incidence of clinically significant
      bleeding, side effects, and cost of therapy in mechanically ventilated trauma
      patients at high risk for stress ulcers who received simplified omeprazole
      suspension (SOS). METHODS: Prospective, evaluative study in a Level I trauma
      center. Mechanically ventilated trauma patients admitted with at least one
      additional risk factor for stress ulcer development received SOS for stress ulcer
      prophylaxis. RESULTS: Sixty trauma patients were enrolled. The mean Injury
      Severity Score was 27.3. After starting SOS, there were no cases of clinically
      significant upper gastrointestinal bleeding related to stress ulceration.
      Baseline pH was 3.3, and mean gastric pH after SOS was increased to 6.7 (p <
      0.005). There were no adverse effects thought to be related to omeprazole
      suspension. Incidence of nosocomial pneumonia after beginning SOS was 28.3%. The
      cost of acquisition plus administration of SOS was $13.13 per day, whereas the
      cost of drug acquisition alone was $3.83 per day. CONCLUSION: In a prospective,
      evaluative study of 60 trauma patients who required mechanical ventilation and
      had at least one additional risk factor for stress ulcer development, omeprazole
      suspension prevented clinically significant gastrointestinal bleeding, maintained
      excellent control of gastric pH, produced no toxicity, and was the least costly
      medication alternative.

PMID- 9529185
TI  - Failed rapid sequence intubation in trauma patients: esophageal tracheal
      combitube is a useful adjunct.
AB  - OBJECTIVE: To characterize the use of the esophageal tracheal combitube (ETC) in
      trauma patients who fail orotracheal rapid sequence intubation (RSI). DESIGN:
      Prospective protocol design and retrospective chart review. MATERIALS AND
      METHODS: Flight nurses were trained in the use of the ETC by mannequin
      simulation, videotape review, and didactic sessions. ETC insertion was attempted
      after failure of two or more attempts at orotracheal RSI. Over a 12-month period,
      12 patients had ETC insertion, and 10 cases qualified for review. Injuries,
      number of failed orotracheal RSI attempts, definitive airway, initial arterial
      blood gas results, and outcome were recorded. RESULTS: ETC insertion was
      successful in all 10 patients in whom it was attempted. Definitive airway control
      was achieved by conversion to orotracheal intubation in seven patients, emergency
      department cricothyroidotomy in one patient, and operative room tracheostomy in
      two patients. No patient died because of failure to control the airway. Seven
      patients requiring ETC had mandible fractures. CONCLUSION: ETC insertion is an
      effective method of airway control in trauma patients who fail orotracheal RSI.
      It may be particularly useful in the patient with maxillofacial trauma and offers
      a practical alternative to surgical cricothyroidotomy in difficult airway
      situations.

PMID- 9529186
TI  - Balloon tamponade for bleeding control in penetrating liver injuries.

PMID- 9529187
TI  - On the possible role of positive end-expiratory pressure ventilation in the
      treatment of chylothorax caused by blunt chest trauma.
AB  - Recent reports on the treatment of chylothorax postulate a benefit to ventilator
      therapy, especially using positive end-expiratory pressure (PEEP). This report
      describes the use of mechanical ventilation with PEEP in the management of a 24
      year-old male motorcyclist who sustained a ligamentous Chance fracture of the
      thoracic spine at the T6-7 level with bilateral traumatic chylothorax. Treatment
      of the chylothorax consisted of high PEEP ventilation, bilateral chest tube
      thoracostomies, and total parenteral nutrition. The chylothoraces resolved within
      4 days of treatment and mechanical ventilation was stopped. Ventilator therapy of
      traumatic chylothorax and the physiologic grounds for its use are discussed. A
      review of the literature and experimental evidence seem to suggest that
      ventilator treatment of traumatic chylothoraces is effective.

PMID- 9529188
TI  - A case of Stanford type A acute aortic dissection caused by blunt chest trauma.

PMID- 9529189
TI  - Endovascular treatment of a traumatic subclavian artery aneurysm.

PMID- 9529190
TI  - Anomalous vertebral artery anatomy and the consequences of penetrating vascular
      injuries.

PMID- 9529191
TI  - A penetrating mediastinal tracheal injury.

PMID- 9529192
TI  - Pancreatic duct injury: intraoperative endoscopic transpancreatic drainage of
      parapancreatic abscess.

PMID- 9529193
TI  - Spinal epidural hematoma and ankylosing spondylitis: case report and review of
      the literature.

PMID- 9529194
TI  - Acute myelinolysis in the cervical spinal cord.

PMID- 9529195
TI  - Laparoscopic management of an enlarging subcapsular splenic hematoma: case
      report.

PMID- 9529196
TI  - Handlebar hernia: a rare traumatic abdominal wall hernia.

PMID- 9529197
TI  - The balance between oxygen supply and demand in the intestine can be assessed by
      measuring the difference between arterial and intramucosal PCO2 (P[t-a]CO2),
      estimated by means of a gastric tonometer.

PMID- 9529198
TI  - Selective decontamination of the digestive tract (SDD) in multiple trauma
      patients.

PMID- 9529199
TI  - Static-electric field induction by a silicone cushion for the treatment of
      hypertrophic and keloid scars.
AB  - Silicone gel and silicone occlusive sheeting are widely used at present for the
      treatment of hypertrophic and keloid scars, without any scientific explanation as
      to their mode of action. In a recent paper the possibility was raised that static
      electricity generated by friction-activated silicone sheeting could be the reason
      for this effect, and that it can, with time, cause involution of hypertrophic and
      keloid scars. The objective of this study was to test this hypothesis and to
      observe whether a continuous and also an increased negatively charged static
      electric field will shorten the treatment period. A device to implement these
      requirements gradually evolved over a 5-year period. A number of prototypes were
      tested until the final product was attained. Some of the patients in this study
      were treated initially with a silicone sponge inserted in the cushion. Later this
      version was changed to the final design described herein. A silicone cushion was
      developed with the purpose of increasing a negative static-electric charge to
      accelerate the regression process. The cushion is custom-made using a silicone
      occlusive sheeting envelope of 0.75-mm thickness, which does not deteriorate with
      use, and is partially filled with high viscosity silicone oil. Its edges are
      sealed, and its size is designed to extend a little beyond the scarred area.
      Static electricity readings, generated by activating the cushion by pumping
      action with the fingers, stretching or deforming the cushion, are invariably much
      higher when compared with those obtained with silicone occlusive sheeting and
      silicone gel sheeting. The interaction between the negatively charged ions of the
      cushion and the ionic charges of the tissue fluids may be the critical factor in
      achieving hypertrophic and keloid scars involution. Of the 30 patients enrolled
      in the study, 3 patients dropped out. Treatment with the silicone cushions
      yielded 63.3 percent cessation of itching and burning followed by pallor and
      flattening of the scar, some markedly so, over a few weeks to 6-month period. An
      additional 26.6 percent had their scars resolved in up to 12 months of treatment.
      Good contact of the cushion over the scar has been shown to be important in this
      clinical trial, and much creativity is needed for making elastic strap bindings
      that ensure this contact. The clinical trials extended over a 12-month period.
      Ten patients (33.3 percent) who had recalcitrant scars with little response to
      the use of the silicone cushion were given intralesional corticosteroid
      injections, in addition to the continued use of the cushion, resulting in a
      fairly rapid resolution of these scars over a period of months to a year.

PMID- 9529200
TI  - Limited value of preoperative cervical vascular imaging in patients with
      velocardiofacial syndrome.
AB  - The purpose of this two-part study was to evaluate the safety of surgical
      management of speech production disorders in patients with velocardiofacial
      syndrome without preoperative cervical vascular imaging studies. Anomalous
      internal carotid arteries have been shown to be a frequent feature of
      velocardiofacial syndrome. These vessels pose a potential risk for hemorrhage
      during velopharyngeal narrowing procedures. Magnetic resonance angiography, and
      other forms of cervical vascular imaging studies such as computerized tomography,
      have been advocated as aids to surgery by defining the preoperative vascular
      anatomy. However, it remains unclear whether these studies alter either the
      conduct or outcome of operations on the velopharynx. In the first part of this
      study, we reviewed the charts and videonasendoscopic evaluations of 39
      consecutive patients with confirmed or suspected velocardiofacial syndrome who
      underwent sphincter pharyngoplasty or pharyngeal flap from 1978 to 1996. The
      charts were reviewed to determine (1) the frequency of identification of abnormal
      pharyngeal pulsations; (2) whether such pulsations affected the conduct of the
      operative procedure; and (3) whether the presence of pulsations affected surgical
      morbidity and/or surgical outcome. None of the patients underwent any type of
      cervical vascular imaging study. In the second part of this study, we surveyed
      plastic surgeons with numerous years of experience participating on cleft
      craniofacial teams, to ascertain practice patterns relating to the management of
      patients with velocardiofacial syndrome. The questions related specifically to
      the surgeons' behavior in relation to angiography and their awareness of any
      cases of surgical morbidity related to the cervical vascular system in patients
      with velocardiofacial syndrome. We were interested in discerning both how
      commonly this situation arises clinically and the distribution of the various
      types of operative procedures in common use. Of our 39 patients, 10 patients (26
      percent) had detectable pulsations on preoperative nasendoscopy. Of these, five
      patients underwent sphincter pharyngoplasty and five underwent pharyngeal flap
      procedures. Preoperative instrumental and intraoperative clinical assessment of
      pulsatile vessels allowed velopharyngeal reconstruction in all patients without
      surgical morbidity. Results of the questionnaire indicated that most cleft
      surgeons do not routinely order cervical vascular imaging studies for all of
      their patients with velocardiofacial syndrome. About half of the respondents
      indicated that their operative approach was influenced by information obtained
      from angiographic studies. None of the surgeons queried were aware of any cases
      of surgical morbidity related to the cervical vascular system in patients with
      velocardiofacial syndrome. Nearly 50 percent of surgeons use pharyngeal flap
      procedures most frequently, whereas 22 percent of surgeons use sphincter
      pharyngoplasty most frequently. Results of this study support the safety of
      sphincter pharyngoplasty or pharyngeal flap procedures in patients with
      velocardiofacial syndrome without preparatory angiography. These procedures can
      be performed safely, even in patients having aberrant velopharyngeal pulsations.
      Given the market cost of magnetic resonance angiography ($1600), one must
      question the cost-efficacy of magnetic resonance angiography for routine use in
      the velocardiofacial syndrome population.

PMID- 9529201
TI  - The role of Muller's muscle reconsidered.
AB  - It is a traditional teaching that the levator aponeurosis is the main transmitter
      of the levator palpebrae muscle. However, there are several points that raise
      doubts in this fundamental concept of the levator aponeurosis as being the
      primary interconnecting mechanism in upper lid elevation. Despite the structural
      integrity of the levator complex, drooping of the upper eyelids is seen to
      develop in situations such as Horner's syndrome and in times of excessive fatigue
      and sleepiness. Amid the controversy in the literature regarding the specific
      role of the levator aponeurosis in the lid-elevating mechanism, we have observed
      that the levator aponeurosis fails to make constant attachment to the tarsal
      plate. This has led us to speculate on the possible role of the posterior lamella
      - Muller's muscle - as the primary transmitter of the levator muscle action to
      the tarsal plate.

PMID- 9529202
TI  - Quantification of dynamic velopharyngeal port excursion following sphincter
      pharyngoplasty.
AB  - The sphincter pharyngoplasty is a surgical procedure designed to correct
      velopharyngeal dysfunction. Its advocates cite the theoretical advantage of its
      induction of dynamic activity of the neovelopharyngeal port, but this dynamic
      activity has yet to be quantitatively demonstrated in the literature. The purpose
      of this study was to quantify postoperative velopharyngeal dynamism and to
      document the results of intervention outcome on sphincteric excursion
      measurements from minimal-to-maximal orifice closure. We conducted a 7-year
      retrospective review of speech videofluoroscopy evaluations in patients who had
      undergone sphincter pharyngoplasty in our center. Between 1989 and 1994, there
      were 58 patients so treated for postpalatoplasty velopharyngeal dysfunction by
      two surgeons using the same operative technique. Patients for whom sphincter
      pharyngoplasty was recommended fulfilled both of the following criteria: (1)
      velopharyngeal dysfunction caused by an anatomic, myoneural, or combined
      deficiency of the velopharyngeal sphincter that would not be expected to be
      managed by speech therapy alone, and (2) preoperative videonasendoscopy and
      speech videofluoroscopic studies that demonstrated large-gap coronal, circular,
      or bow-tie closure patterns or velopharyngeal hypodynamism. Of the original 58
      patients, 24 underwent postoperative speech videofluoroscopic evaluations with
      basal views. Of these, 20 of the evaluations (83 percent) were of adequate
      quality to be included in a research study. Still images showing maximum and
      minimum excursion of the sphincter in basal view were obtained. To test for
      observer reliability, the speech videofluoroscopic studies were randomized and
      presented for measurement to the same individual on two occasions, each session
      separated by a 1-month time interval. Topographic imaging software was used to
      obtain maximum and minimum measurements to within 0.1 mm. Partitioning the
      variance of the data showed that measurement variability was a very small portion
      of the total, and that difference between the minimum and maximum values was the
      largest source of variability. Of the total variability in the data, 64.0 percent
      originated in the minimum/maximum difference, 34.3 percent came from patient
      variability, and only 1.7 percent resulted from original or repeat measurements.
      The patient variability may be exaggerated because of variability in the scale of
      measurement. Results of this study indicate a quantifiable and statistically
      significant difference in maximum-to-minimum excursion of sphincteric closure.
      Sphincter pharyngoplasty appears to be dynamic in the majority of cases.

PMID- 9529203
TI  - Intralesional bare fiber laser treatment of hemangioma of infancy.
AB  - The purpose of this study is to examine the effects of intralesional fiber with
      the KTP laser on treatment of hemangiomas in infancy. A series of 12 patients (1
      month to 3 1/2 years) were treated for hemangioma of the head and neck regions.
      Results were as follows: 92 percent, > 50 percent reduction at 3 months; 8
      percent, > 50 percent reduction at 6 months. To achieve these results, 50 percent
      required two treatments (six cases), and 8 percent required three treatments (one
      case). Improvement of function was clearly in the proliferative phase. Lesions on
      three patients (25 percent) ulcerated following laser therapy. No other side
      effects or complications were noted. Intralesional fiber therapy is determined to
      be effective and safely used to induce involution of voluminous hemangiomas of
      the face and neck regions.

PMID- 9529204
TI  - Undermining of the scalp: quantitative effects.
AB  - The aim of the present study was to evaluate to what extent undermining affects
      the closing-tension of scalp defects to quantify the surgery-related benefits
      provided by this procedure. Data were collected by stepwise loading in 10
      patients, 20 scalp flaps (obtained by a reversed Y scalp incision), and three
      different degrees of subgaleal undermining (1, 5, and 15 cm). The obtained data
      confirmed the value of undermining to diminish the tension on wound margins when
      closing a scalp defect. There was a progressive decrease in tension required to
      advance the wound edge when the amount of undermining was sequentially increased.
      Most of this reduction occurred with the 5-cm undermining, although statistically
      the 15-cm undermining also resulted in a significant decrease in the tension
      required to close the defect. Mean 83.3- and 92.2-percent reductions of the
      closing tension were obtained with 5 cm and 15 cm of undermining, respectively,
      compared with that achieved by the 1-cm undermining with the same width of
      defect.

PMID- 9529205
TI  - Commissure-based buccal mucosal flap.
AB  - Commissure-based buccal mucosal flaps extending to the retromolar trigone have
      been used for anterior intraoral mucosal defects. The flap was utilized
      successfully in 26 patients who had vermilion defect (14 cases), obliteration of
      the anterior gingivobuccal sulcus (8 cases), and anterior maxillary defect (4
      cases).

PMID- 9529206
TI  - Immediate breast reconstruction for breast carcinoma using the periareolar
      approach.
AB  - Skin-sparing mastectomy with immediate breast reconstruction has shown to be
      oncologically safe while providing dependable aesthetic results. However, flap
      inset into the skin defect of the excised biopsy site and nipple-areola complex
      often results in a patchlike effect and transverse scars. By keeping the
      mastectomy incision solely around the areola, all breast skin can be preserved.
      Thus, in immediate breast reconstruction with replacement of the nipple and
      areola by a small skin island from a deepithelialized TRAM flap or latissimus
      dorsi muscle flap, the scar is kept at the natural border between areola and
      breast skin. Reconstruction of the nipple-areola complex further helps to
      camouflage the incision line. This may result in the best possible aesthetic
      outcome after mastectomy to date. The technique has been used in 17 breast cancer
      patients (intraductal cancer, n = 5; T1/T2 ductal cancer, n = 13) with good to
      excellent results. No local or distant recurrences have been seen; however, mean
      follow-up time is short (10 months). As the procedure of choice, a free TRAM flap
      was performed in nine patients for immediate reconstruction. The other eight
      patients were too slim for an autologous reconstruction; therefore, a latissimus
      dorsi muscle flap with a small skin island and a silicone implant were used.
      There were no major complications in either group. In contrast to traditional
      skin-sparing mastectomy, all breast skin is preserved with the periareolar
      approach. Therefore, special surgical expertise is required to ensure tumor free
      margins, especially with respect to the skin overlying the tumor. If these
      requirements are met, excellent results in breast reconstruction are amenable
      with adequate oncologic safety.

PMID- 9529207
TI  - Sliding door technique for the repair of midline incisional hernias.
AB  - We describe a technique that enables the autologous repair of large midline
      incisional hernias by restoring the functional musculoaponeurotic support of the
      abdominal wall. Unlike other methods of hernia repair, the essential step of the
      sliding door technique is the complete release of the rectus abdominis muscles
      from the anterior and posterior layers of their sheaths. The released muscles are
      thus overlapped and sutured together without tension. Another step of the
      technique is the release of both rectus sheaths by incising the aponeuroses of
      the external oblique muscles. We report on the use of this technique in 10
      patients with midline incisional hernias (mean size of the abdominal
      musculofascial defect 14 x 11 cm). The patients were examined 14 months to 5.5
      years after hernia repair. Two postoperative complications occurred: one marginal
      skin necrosis and one subcutaneous seroma. Recurrences were not observed.
      Ultrasound examination showed that the rectus muscles maintained their overlapped
      position postoperatively. Clinical muscle testing indicated that the strength of
      the released rectus muscles provides functional support to the reconstructed
      anterior abdominal wall.

PMID- 9529208
TI  - Outcome assessment of an in-hospital cross-functional wound care team.
AB  - A multidisciplinary wound care team was developed at the Medical College of
      Pennsylvania Hospital in 1993 to standardize wound management, appropriately
      allocate resources, prevent the occurrence of hospital-acquired decubitus ulcers,
      and effectively manage existing pressure ulcers. This report presents 4 years of
      prevalence survey data (n = 690 patients over 4 years), which affords an outcome
      analysis regarding the efficacy of the multidisciplinary wound care team. A
      significant reduction in the number of patients with pressure ulcers, hospital
      acquired pressure ulcers, and patients with hospital acquired ulcers occurred.
      There was, also, a significant improvement in skin integrity documentation, and
      in the implementation of nutritional assessments. These findings suggest that the
      multidisciplinary wound care team has been an effective means of gaining some
      control of decubitus ulcers, which are associated with increased patient
      morbidity and have an adverse economic impact on hospitals.

PMID- 9529209
TI  - Treatment of complex postoperative lumbosacral wounds in nonparalyzed patients.
AB  - Postoperative infections after back operations can produce complex wounds with
      myonecrosis, deep dead space, and exposed orthopedic hardware, bone, and dura.
      Three ambulatory patients with complex postoperative back wounds that resulted
      from infections were treated successfully with antibiotics, debridement,
      irrigation, and closure of deep dead space with a superior gluteal muscle flap.
      Several surgical maneuvers can be performed to increase the length of the
      superior gluteal muscle flap. The inferior portion of the gluteus maximus was
      left intact to preserve gluteus maximus function. All three patients obtained
      healed wounds. The exposed A.O. plating system was not removed. There has not
      been any recurrence of infections. The superior gluteal muscle flap is a
      reasonable flap to fill deep dead space in the low back and has some advantages
      over free flaps.

PMID- 9529210
TI  - Prospective study of the accuracy of the surgeon's diagnosis in 2000 excised skin
      tumors.
AB  - Expeditious yet efficacious removal of skin tumors is a common responsibility for
      the plastic surgeon. The need to minimize potential risks for mortality or
      morbidity from undue or excessive surgical resections and to control costs by
      avoiding unnecessary procedures behooves us to make a precise clinical diagnosis
      preceding any decision even for such "minor" surgery. Just how accurate these
      decisions can be expected to be for a typical surgical practice was scrutinized
      by means of this prospective 4-year study involving the resection of 2058 skin
      lesions. Each lesion was initially assigned a clinical diagnosis after a brief
      gross examination and then compared with the pathology report, which was always
      considered to be the correct answer. Within these parameters, only 65 percent of
      all tumors were identified correctly preoperatively. Two-thirds of all lesions
      were benign. Three-quarters of benign lesions were as assumed, and 92 percent of
      all presumed benign lesions were benign even if incorrectly identified initially,
      whereas fortunately only 3 percent proved to be malignant. On the other hand,
      only three-fifths of malignant lesions were identified correctly clinically, yet
      only 11 percent were benign, implying that most such lesions properly deserved
      excision anyway. Therefore, approximately 90 percent of all lesions whether
      benign or malignant were removed appropriately without compromising the patient,
      but to expect a clinical acumen of 100 percent in this setting may not be
      realistic. The accuracy of the surgeon in identifying lesions as probably benign
      was certainly high enough that cost-containment mechanisms designed to deny
      authorization for their removal probably would be justifiable and difficult to
      appeal. Any suspicious or equivocal lesions still will require mandatory
      intervention despite such constraints, because often only histologic examination
      will allow a definitive diagnosis.

PMID- 9529212
TI  - The effect of an implantable Doppler probe on the salvage of microvascular tissue
      transplants.
AB  - One hundred forty-seven flaps in 135 consecutive patients undergoing
      microvascular transplantation were monitored using a miniature Doppler ultrasonic
      probe. Using a modification of a technique described previously by Swartz, the
      probes were secured to the outflow vein of the flap with Vicryl mesh. Twenty
      instances of thrombosis or spasm were detected in 16 patients, and all flaps were
      salvaged (100 percent). There were four false positive and no false negative
      results. This probe allows for safe, continuous monitoring of flap blood flow,
      which permits the rapid detection and hence rapid treatment of postoperative
      complications. Our experience suggests that a significant improvement in the
      salvage rate of microvascular transplants may be attainable with the use of this
      device.

PMID- 9529211
TI  - Use of 20 cm or longer interposition vein grafts in free flap reconstruction of
      the trunk.
AB  - Between January of 1993 and September of 1995, six microsurgical free tissue
      transplants were performed using saphenous vein grafts ranging from 20 to 39 cm
      in length. All six free flaps survived. Two wounds were caused by radiation
      injury and two by tumor resection. The remaining two free flaps were performed
      for contour deformity and spinal cord coverage. All of the recipient sites were
      located on the trunk. In each case, an arteriovenous loop was created before the
      microvascular anastomosis to the free flap. There was one arterial thrombosis
      requiring thrombectomy and revision of the anastomosis. Three patients developed
      minor wound complications that responded to local wound care. Each of the flaps
      successfully provided wound coverage, and in two cases the flaps tolerated
      further radiation results. Long interposition vein grafts can be used for
      difficult microsurgical reconstructive procedures with reliable results when no
      local recipient vessels are available. Versatility is therefore afforded in
      placement of the flap and the choice of recipient vessels, making this option a
      useful one in the treatment of complex wounds of the trunk.

PMID- 9529213
TI  - Preliminary studies of the use of nail as a material for reconstructive or
      cosmetic surgery.
AB  - The purpose of this study was to assess the biocompatibility and stability of
      implanted nail as a preliminary step in the assessment of its potential as a
      material for small scale reconstructive or cosmetic surgery. Rat nails were
      placed subcutaneously in the back of 12 Lewis rats, which were then sacrificed in
      groups of 4 at 4, 8, and 12 months for macroscopic and microscopic examination of
      the implants. A layer of strongly adherent connective tissue, containing
      inflammatory cells, had formed around the nails at 4 months, but by 8 to 12
      months this reaction had subsided, leaving the nails imbedded in connective
      tissue adhering to the dermal wall, with no evidence of implant rejection,
      granuloma formation, or degradation. The results suggest that nail merits further
      study as a surgical implant material, because of its staying power and lack of
      immunogenicity.

PMID- 9529214
TI  - Effects of blood flow and venous network on the survival of the arterialized
      venous flap.
AB  - The purpose of this study was to evaluate further factors that could explain the
      survival mechanism in the arterialized venous flap. The authors used 16 canines
      to investigate the survival rate and pattern of the arterialized venous flap and
      compared the results with those of the conventional saphenous flap. The number
      and distribution of draining veins in the arterialized venous flap group were
      varied to observe their impact on the survival rate and pattern. Gross
      examination of venous network, blood gas, venogram, blood pressure, and
      histologic study were also carried out. Although there was no significant
      difference in final survival rate between conventional flap and arterialized
      venous flap with two efferent veins (p > 0.01), that of the arterialized venous
      flap increased significantly as the number of draining veins increased. Blood gas
      analysis showed that more effective oxygen consumption took place when the number
      of draining veins increased. By measuring the blood flow and volume at 8 hours
      after the operation with a laser Doppler flowmeter, it was possible to predict
      the necrosis of the arterialized venous flap. Attachment to a high pressure
      arterial blood flow system induced smooth muscle proliferation and neogrowth of
      elastic fibers in the veins. Furthermore, progressive narrowing of the lumen
      hastened the development of a collateral circulation, demonstrated on a venogram
      by the tortuous vessels and neovascularization up to the flap margin. To make it
      possible to predict and achieve complete survival of the arterialized venous
      flap, the following criteria must be considered: (a) an arterialized venous flap
      should be designed to contain most of the venous network in the center, (b) the
      arterial inflow has to be anastomosed to one afferent vein, (c) two or more
      efferent veins should drain the arterialized venous flap.

PMID- 9529215
TI  - Stimulation of angiogenesis to improve the viability of prefabricated flaps.
AB  - The cutaneous area in a prefabricated myocutaneous flap surviving after elevation
      is dependent on the rate and amount of vascular ingrowth that occurs from the
      underlying muscle. Two modalities, basic fibroblast growth factor and hyperbaric
      oxygen, were used separately and together in a prefabricated myocutaneous flap
      animal model to improve flap survival. The semimembranous muscle, based on the
      saphenous vessels of 40 female Wistar rats weighing between 250 and 325 grams,
      was tunneled under the ipsilateral abdominal skin and sutured in place. A 3 x 5
      cm silicone sheet was placed beneath the muscle flap, and the ipsilateral
      epigastric vessels were ligated. Four groups of 10 animals each received one of
      the following treatment regimes: a 1-ml normal saline infusion into the saphenous
      arterial pedicle, a 1-ml infusion of basic fibroblast growth factor (1.0
      microg/gm of muscle), a 1-ml normal saline infusion and 14 hyperbaric oxygen
      treatments, or a 1-ml basic fibroblast growth factor infusion and 14 hyperbaric
      oxygen treatments. After 1 week, the muscle, still based on the saphenous
      vessels, was elevated with a 3 x 5-cm abdominal skin paddle. The flap was sutured
      back in place, leaving the silicone sheet intact. The surviving area of each flap
      was measured 1 week later after it had demarcated into viable and necrotic
      regions. Laser Doppler skin perfusion measurements were taken before and after
      flap elevation and before animal euthanasia. Sixteen flaps, 4 in each group, were
      examined histologically for vascularity by means of hematoxylin and eosin
      staining. There was a statistically significant increase in flap survival area
      when either basic fibroblast growth factor or hyperbaric oxygen was used alone.
      Further improvement was noted with combination therapy. Histology confirmed
      improved vascularity in the basic fibroblast growth factor and hyperbaric oxygen
      treated flaps. This study shows a significant and reliable increase in the area
      of prefabricated myocutaneous flap survival using either basic fibroblast growth
      factor or hyperbaric oxygen. There is a further complementary effect when these
      two modalities are combined, leading to near complete flap survival through
      improved vascularity.

PMID- 9529216
TI  - Mode of vascularization of control and basic fibroblast growth factor-stimulated
      prefabricated skin flaps.
AB  - This study, using 62 rabbits, examines the rate and pattern of vascular outgrowth
      from a subcutaneously implanted vascular pedicle, how the newly formed vessels
      connect to preexisting skin vessels, and whether local application of basic
      fibroblast growth factor can accelerate the angiogenic process. When the femoral
      artery and vein of rabbits are implanted beneath the skin, angiogenesis from both
      the pedicle and small blood vessels within the adjacent skin begins within 3
      days. Perfusion with India ink reveals connections between the pedicle and dermal
      vessels as early as 5 days after implantation of the pedicle. Provided the
      pedicle does not thrombose, skin flaps based on it may survive completely when
      elevated as early as 2 weeks after implantation. Flap survival depends on the
      development of a small number of vascular connections between vessels arising
      from the pedicle and preexisting dermal vessels. If elevation is delayed until 4
      weeks after implantation a flap may survive even if its pedicle has thrombosed.
      Prolonged release of basic fibroblast growth factor adjacent to the pedicle
      significantly increases the survival of flaps elevated 1 week after implantation
      but does not alter the survival of flaps elevated at 2 and 4 weeks.

PMID- 9529217
TI  - Evaluation of expanded polytetrafluoroethylene as a soft-tissue filling
      substance: an analysis of design-related implant behavior using the porcine skin
      model.
AB  - Soft-tissue augmentation using the synthetic nonfluid biomaterial expanded
      polytetrafluoroethylene (ePTFE) has been supported by number of recent reports
      citing the favorable characteristics of biocompatibility, soft and natural feel,
      ease of use, and permanent augmentation. Concern has been expressed about this
      application for ePTFE material because of the proximity of the implants to the
      skin surface and potential problems with infection and extrusion. We evaluated
      the behavior of a series of specific ePTFE implant designs using a long-term
      subcutaneous augmentation model. By using a porcine model, 466 implants of ePTFE
      in the form of strips, rolls, or tubes were placed using a percutaneous insertion
      device subcutaneously over the dorsum and face. The animals were divided into
      three study groups by length of implantation (3 weeks, control; 6 months,
      intermediate term; and 12 months, long-term) and en-bloc tissue specimens,
      including skin, implants, and underlying soft tissue, were harvested for gross
      and histologic examination. Implants were removed at the earliest sign of
      infection, exposure, or extrusion and the difficulty of removal was ascertained
      and recorded. These data reveal that ePTFE material elicits acceptable levels of
      tissue activity with low extrusion rates over the short and long term supporting
      its use for soft-tissue augmentation. The data show a clear difference, however,
      in the host response and behavior of the implants for this application based on
      shape or design. A statistically significant difference in the low, but
      measurable, extrusion rates was observed amongst these implant designs. ePTFE
      tubes showed greater stability and predictable augmentation over other implant
      designs for soft-tissue augmentation and seem to represent a substantial
      improvement for this application.

PMID- 9529218
TI  - Ultraviolet exposure influences laser-induced wounds, scars, and
      hyperpigmentation: a murine study.
AB  - Laser therapy is today considered the treatment of choice for vascular skin
      lesions, which commonly are located on the face and, therefore, frequently are
      exposed to sunlight. The purpose of this study was to examine whether
      preoperative and postoperative ultraviolet irradiation influences the development
      of laser-induced side effects. We laser-treated hairless mice with a copper vapor
      laser; three different intensities were used at a constant pulse duration.
      Simulated solar ultraviolet radiation was administered either before the laser
      treatment (3 consecutive days, daily doses of 2.48 J/cm2) or after the laser
      treatment (four times weekly in 4 weeks, daily doses of 1.66 J/cm2). Laser
      induced wounds, scars, and hyperpigmentation were evaluated by macroscopic,
      histologic, and biochemical examinations. Preoperative ultraviolet exposure
      enlarged the laser-induced wounds and the areas with texture change at some of
      the laser intensities used. However, the most pronounced effect was seen for
      postoperative ultraviolet-irradiated mice. These mice developed, at some of the
      laser intensities, a higher incidence of bulging infiltration as well as higher
      degrees of fibrosis and hyperpigmentation, thus developing a poor cosmetic
      appearance. Furthermore, ultraviolet irradiation after laser treatment resulted
      in slowly healing wounds of reduced size, indicating deep, constricted skin
      damage. We conclude that ultraviolet exposure before and after copper vapor laser
      treatment increases the risk of inducing side effects from dermatological laser
      treatment.

PMID- 9529219
TI  - Complications of orbital reconstruction: misplacement of bone grafts within the
      intramuscular cone.

PMID- 9529220
TI  - Reconstruction of Wegener's nasal deformity using bilateral facial artery
      musculomucosal flaps.

PMID- 9529221
TI  - Quarter vermillion flap: a method for symmetrical lower vermillion
      reconstruction.

PMID- 9529222
TI  - The reverse temporoparietal fascia flap.

PMID- 9529223
TI  - Radial forearm free flap tracheal reconstruction after parastomal tumor
      resection.

PMID- 9529224
TI  - Tulip flap for reconstruction of the central tubercle in cleft lip patients.

PMID- 9529225
TI  - Simple fixation method for unstable zygomatic arch fracture using double
      Kirschner's wires.

PMID- 9529226
TI  - Relocation of the displaced nipple-areola by reciprocal skin grafts.

PMID- 9529227
TI  - Footplates of the medial crura.
AB  - The purpose of this combined prospective and retrospective study was to review
      the abnormalities of the footplates of the medial crura, their surgical
      correction, and the dynamic changes that result from footplate alteration.
      Prospectively, measurements of 40 footplates were obtained during 20 consecutive
      primary rhinoplasties. The distance between the footplates at their most
      posterocaudal position was measured, along with the thickness, length, and width
      of the footplates. The shape of the nostrils was also observed and correlated to
      the form of the footplates. The distance between the footplates ranged from 7.5
      to 15 mm, the average being 11.4 mm. The length of the footplates ranged from 4
      to 7.5 mm, the average being 5.81 mm. The thickness of the footplates averaged
      1.06 mm, ranging from 0.80 to 1.5 mm. The width of the footplates ranged from 2.5
      to 7.0 mm, averaging 4.48 mm. In a retrospective review of 295 consecutive
      rhinoplasties, footplates were altered in 76 cases (25.8 percent). Of these
      cases, 29 procedures (9.8 percent) were performed to narrow the columella base
      and to advance the subnasale: on 24 patients (8.1 percent), the goal of this
      maneuver was to narrow the columella base only; on 5 patients (1.7 percent), the
      operation was conducted to aid in increasing the tip projection, provide a better
      foundation for the tip, advance the subnasale caudally, and narrow the alar base.
      Asymmetry of the columella was corrected in 16 patients (5.4 percent), and
      footplates were resected primarily to reduce the tip projection in 2 patients
      (0.7 percent). A detailed analysis of the nasal base will dictate one of the
      following courses pertaining to footplate alteration. If the patient exhibits an
      overprojected tip and divergent footplates, the lateral portion of the footplates
      will be resected partially, then approximated. If the tip is underprojected or
      has normal projection, the divergent footplates will be approximated without
      resection. Should the subnasale and the base of the columella be protruding, the
      soft tissue between the footplates will be removed to avoid excess fullness in
      this site as a result of the approximation of the footplate. However, when the
      footplates are divergent, the columella base and nasal spine area are often
      retracted, setting an auspicious stage for approximation of the footplates
      without having to excise the soft tissue. This maneuver not only narrows the
      columella base, it also advances it caudally. Longstanding caudal deviation of
      the septum may also create asymmetry of the footplates, which will not respond to
      mere repositioning of the septum, and often requires repositioning of the
      footplates with mobilization and fixation to the contralateral footplates.

PMID- 9529228
TI  - A review of explantation in 240 symptomatic women: a description of explantation
      and capsulectomy with reconstruction using a periareolar technique.
AB  - A review of 240 women who were explanted is presented. The analysis reviewed
      physical problems, systemic complaints, and whether explantation relieved
      symptoms and improved patients.

PMID- 9529229
TI  - Ultrastructural study of the skin after facial chemical peels and the effect of
      moisturization on wound healing.
AB  - Ultrastructural changes occurring in the skin at early times after chemical peels
      as well as effects on the wound healing with moisturization after these peels
      have been examined. This study evaluated the changes seen in the skin 3 days and
      5 days after 35% trichloroacetic acid peels, and the effect of moisturization on
      this healing was evaluated. Biopsies at 3 days showed an outermost layer of
      necrotic stratum corneum and stratum granulosum and an underlying layer of new
      stratum corneum. There were increased cytoplasmic vacuoles in the keratinocytes
      of the stratum spinosum, stratum granulosum, and stratum basale layers. There was
      extensive intercellular spacing between the basal keratinocytes. At 5 days the
      necrotic layer of stratum corneum and stratum granulosum was gone. The lower
      epidermis at 5 days showed less intercellular spacing, and there was less
      vacuolization within keratinocytes. In seven of eight patients treated with
      moisturization after the peel (p = 0.0325), the ultrastructural changes at 5 days
      were consistent with a more advanced state of healing compared with those that
      were treated dry. Ultrastructural morphology at this time showed less
      intercellular spacing and fewer cytoplasmic vacuoles, indicative of an advanced
      state of wound repair. These moisturized skin specimens had returned to an almost
      normal state of structure compared with the skin that had been treated dry.

PMID- 9529230
TI  - Certificate of Added Qualifications: CAQ or "QAC"ery?

PMID- 9529231
TI  - Service and unity: the 1997 ASPRS presidential address. American Society of
      Plastic and Reconstructive Surgeons.

PMID- 9529232
TI  - Competitive forces and academic plastic surgery.
AB  - Economic constraints developing as a result of rising health care costs in the
      United States pose significant challenges for and threats to the survival of
      academic plastic surgery. Declining clinical revenues, competition for patients
      and resources from other health care providers, and reductions in support of its
      education and research efforts necessitate a paradigm shift if it is to survive.
      Questionnaires were used to collect data from 92 of the 100 postgraduate training
      program directors of plastic surgery in the United States. The most common source
      of clinical income on a national basis was indemnity insurance. Sources of
      clinical income varied by region. The majority of programs, 80 percent, report
      that at least 75 percent of the income support for faculty came from practice
      income. Financial support for ancillary and research personnel, in large part,
      came from this same source. Resident salaries and benefits came largely from
      other resources. Generally as population density within the metropolitan area in
      which a program was located increased, so too did the number of competing plastic
      surgeons, including graduates of the program and nonacademic cosmetic and hand
      surgeons. However, levels of competition for cosmetic surgery in smaller
      metropolitan areas of some regions seem to be similar to those reported by
      programs in larger communities. Plastic surgery programs in very competitive
      communities received significantly greater amounts of their income from indemnity
      insurance and self-paying patients than did programs in less competitive
      metropolitan areas. Internal competition from other surgical and nonsurgical
      specialists within the same institution is likewise keen. Virtually all
      respondents, 93 percent, report that their institutions provided patient care in
      a least one designated center of excellence in the following disciplines: hand,
      microsurgery, craniofacial, cleft lip and palate, burn, and cosmetic surgery.
      This study suggests that centers of excellence are more likely to be present in
      metropolitan areas with fewer competing surgeons than in areas with large numbers
      of competing surgeons. The data did not demonstrate that the presence of a center
      of excellence substantially affected the sources or levels of clinical income. To
      survive as an academic entity, program directors must correctly perceive and
      fulfill the needs and wants of its stakeholders, particularly with regard to
      quality of life issues.

PMID- 9529233
TI  - Survey of factors influencing the selection of academic plastic surgeons.
AB  - The purpose of this study was to evaluate the importance of factors influencing
      the selection of candidates for academic positions in plastic surgery. This study
      reports the results of a survey investigating these factors. The survey was
      conducted in 1994, canvassing the chairpersons from the 120 plastic surgery
      programs in the United States and Canada with responses from 91 (76 percent) of
      the plastic surgery programs. The study examined individual accomplishments and
      areas of additional training. Training in a specific area of clinical interest,
      clinical and basic science experience, and training in cosmetic surgery were the
      most highly rated areas of additional training. The ideal time to receive this
      training was also assessed for each area of additional training. Postgraduate
      degrees in basic science, epidemiology, or clinical research were not highly
      rated. The highest rated personal accomplishments were the personal interview,
      letter of reference from the program chairperson, publications, and
      presentations. Despite the survey's attempt to evaluate factors other than
      personal characteristics (i.e., honesty, integrity, affability, etc.) more than
      25 percent of the respondents indicated that these attributes are highly rated
      and cannot be judged separately. The information collected in this survey
      represents an opinion from 1994, which defines some of the factors that are
      considered important when residents and newly trained plastic surgeons are
      considering a career in academic plastic surgery.

PMID- 9529234
TI  - Composite rhytidectomy.

PMID- 9529235
TI  - Fixation screw for jaw fractures.

PMID- 9529236
TI  - Enlargement of the upper third of the ear with use of triple banner flap and
      postauricular island flap.

PMID- 9529237
TI  - The youthful face: tight is not right, repositioning is right.

PMID- 9529238
TI  - A new hair graft canister for graft-counting and preserving in damp medium.

PMID- 9529239
TI  - Simple dressing for nipple reconstruction.

PMID- 9529241
TI  - Overserving the underserved.

PMID- 9529240
TI  - A treatment of ulcers of the heel in leprosy.

PMID- 9529242
TI  - The quality of slides.

PMID- 9529243
TI  - Use of mini-vacuum drains in small surgical wounds.

PMID- 9529244
TI  - Mammalian and Drosophila blood: JAK of all trades?

PMID- 9529245
TI  - Cerebellar LTD: a molecular mechanism of behavioral learning?

PMID- 9529246
TI  - Follow the leader: NK cell receptors for classical and nonclassical MHC class I.

PMID- 9529247
TI  - Splicing regulation in neurons: tinkering with cell-specific control.

PMID- 9529248
TI  - The Ink4a tumor suppressor gene product, p19Arf, interacts with MDM2 and
      neutralizes MDM2's inhibition of p53.
AB  - The INK4a gene encodes two distinct growth inhibitors--the cyclin-dependent
      kinase inhibitor p16Ink4a, which is a component of the Rb pathway, and the tumor
      suppressor p19Arf, which has been functionally linked to p53. Here we show that
      p19Arf potently suppresses oncogenic transformation in primary cells and that
      this function is abrogated when p53 is neutralized by viral oncoproteins and
      dominant-negative mutants but not by the p53 antagonist MDM2. This finding,
      coupled with the observations that p19Arf and MDM2 physically interact and that
      p19Rrf blocks MDM2-induced p53 degradation and transactivational silencing,
      suggests that p19Arf functions mechanistically to prevent MDM2's neutralization
      of p53. Together, our findings ascribe INK4a's potent tumor suppressor activity
      to the cooperative actions of its two protein products and their relation to the
      two central growth control pathways, Rb and p53.

PMID- 9529249
TI  - ARF promotes MDM2 degradation and stabilizes p53: ARF-INK4a locus deletion
      impairs both the Rb and p53 tumor suppression pathways.
AB  - The INK4a-ARF locus encodes two unrelated proteins that both function in tumor
      suppression. p16INK4 binds to and inhibits the activity of CDK4 and CDK6, and ARF
      arrests the cell cycle in a p53-dependent manner. We show here that ARF binds to
      MDM2 and promotes the rapid degradation of MDM2. This interaction is mediated by
      the exon 1beta-encoded N-terminal domain of ARF and a C-terminal region of MDM2.
      ARF-promoted MDM2 degradation is associated with MDM2 modification and concurrent
      p53 stabilization and accumulation. The functional consequence of ARF-regulated
      p53 levels via MDM2 proteolysis is evidenced by the ability of ectopically
      expressed ARF to restore a p53-imposed G1 cell cycle arrest that is otherwise
      abrogated by MDM2. Thus, deletion of the ARF-INK4a locus simultaneously impairs
      both the INK4a-cyclin D/CDK4-RB and the ARF-MDM2-p53 pathways.

PMID- 9529250
TI  - Neuropilin-1 is expressed by endothelial and tumor cells as an isoform-specific
      receptor for vascular endothelial growth factor.
AB  - Vascular endothelial growth factor (VEGF), a major regulator of angiogenesis,
      binds to two receptor tyrosine kinases, KDR/Flk-1 and Flt-1. We now describe the
      purification and the expression cloning from tumor cells of a third VEGF
      receptor, one that binds VEGF165 but not VEGF121. This isoform-specific VEGF
      receptor (VEGF165R) is identical to human neuropilin-1, a receptor for the
      collapsin/semaphorin family that mediates neuronal cell guidance. When
      coexpressed in cells with KDR, neuropilin-1 enhances the binding of VEGF165 to
      KDR and VEGF165-mediated chemotaxis. Conversely, inhibition of VEGF165 binding to
      neuropilin-1 inhibits its binding to KDR and its mitogenic activity for
      endothelial cells. We propose that neuropilin-1 is a novel VEGF receptor that
      modulates VEGF binding to KDR and subsequent bioactivity and therefore may
      regulate VEGF-induced angiogenesis.

PMID- 9529251
TI  - BiP maintains the permeability barrier of the ER membrane by sealing the lumenal
      end of the translocon pore before and early in translocation.
AB  - Secretory proteins are cotranslationally translocated across the mammalian ER
      membrane through an aqueous pore in the translocon while the permeability barrier
      is maintained by a tight ribosome-membrane junction. The lumenal end of the pore
      is also blocked early in translocation. Extraction of soluble lumenal proteins
      from microsomes and reconstitution with purified proteins demonstrate, by
      fluorescence collisional quenching, that BiP seals the lumenal end of this pore.
      BiP also seals translocons that are assembled but are not engaged in
      translocation. These ribosome-free translocons have smaller pores (9-15 A
      diameter versus 40-60 A in functioning translocons) and are generated when
      ribosomes dissociate from functioning translocons with large pores. BiP therefore
      maintains the permeability barrier by sealing both nontranslocating and newly
      targeted translocons.

PMID- 9529252
TI  - SNAREpins: minimal machinery for membrane fusion.
AB  - Recombinant v- and t-SNARE proteins reconstituted into separate lipid bilayer
      vesicles assemble into SNAREpins-SNARE complexes linking two membranes. This
      leads to spontaneous fusion of the docked membranes at physiological temperature.
      Docked unfused intermediates can accumulate at lower temperatures and can fuse
      when brought to physiological temperature. A supply of unassembled v- and t
      SNAREs is needed for these intermediates to form, but not for the fusion that
      follows. These data imply that SNAREpins are the minimal machinery for cellular
      membrane fusion.

PMID- 9529253
TI  - Reactive oxygen intermediates mediate a systemic signal network in the
      establishment of plant immunity.
AB  - Recognition of an avirulent pathogen stimulates an oxidative burst generating O2-
      and H2O2, and these reactive oxygen intermediates (ROIs) cue the induction of
      defense genes and cell death in the development of a restricted lesion. This
      localized hypersensitive response (HR) is accompanied by the development of
      systemic acquired resistance to virulent pathogens. Here we show that inoculation
      of Arabidopsis leaves with avirulent Pseudomonas syringae induces secondary
      oxidative bursts in discrete cells in distant tissues, leading to low-frequency
      systemic micro-HRs. The primary oxidative burst induces these systemic responses,
      and both the primary burst and the secondary microbursts are required for
      systemic immunity. Hence, ROIs mediate a reiterative signal network underlying
      systemic as well as local resistance responses.

PMID- 9529255
TI  - Smad2 signaling in extraembryonic tissues determines anterior-posterior polarity
      of the early mouse embryo.
AB  - Smad proteins transmit TGFbeta signals from the cell surface to the nucleus. Here
      we analyze Smad2 mutant embryos created using ES cell technology. Smad2 function
      is not required for mesoderm production per se, but, rather unexpectedly, in the
      absence of Smad2 the entire epiblast adopts a mesodermal fate giving rise to a
      normal yolk sac and fetal blood cells. In contrast, Smad2 mutants entirely lack
      tissues of the embryonic germ layers. Smad2 signals serve to restrict the site of
      primitive streak formation and establish anterior-posterior identity within the
      epiblast. Chimera experiments demonstrate these essential activities are
      contributed by the extraembryonic tissues. Thus, the extraembryonic tissues play
      critical roles in establishing the body plan during early mouse development.

PMID- 9529254
TI  - UNC-73 activates the Rac GTPase and is required for cell and growth cone
      migrations in C. elegans.
AB  - unc-73 is required for cell migrations and axon guidance in C. elegans and
      encodes overlapping isoforms of 283 and 189 kDa that are closely related to the
      vertebrate Trio and Kalirin proteins, respectively. UNC-73A contains, in order,
      eight spectrin-like repeats, a Dbl/Pleckstrin homology (DH/PH) element, an SH3
      like domain, a second DH/PH element, an immunoglobulin domain, and a fibronectin
      type III domain. UNC-73B terminates just downstream of the SH3-like domain. The
      first DH/PH element specifically activates the Rac GTPase in vitro and stimulates
      actin polymerization when expressed in Rat2 cells. Both functions are eliminated
      by introducing the S1216F mutation of unc-73(rh40) into this DH domain. Our
      results suggest that UNC-73 acts cell autonomously in a protein complex to
      regulate actin dynamics during cell and growth cone migrations.

PMID- 9529256
TI  - Calmodulin regulates L-selectin adhesion molecule expression and function through
      a protease-dependent mechanism.
AB  - Expression of the L-selectin adhesion molecule is rapidly down-regulated upon
      cell activation through proteolysis at a membrane-proximal site. Here we
      demonstrate that calmodulin, an intracellular calcium regulatory protein,
      specifically coprecipitates with L-selectin through a direct association with the
      cytoplasmic domain of L-selectin. Furthermore, calmodulin inhibitors disrupt L
      selectin-dependent adhesion by inducing proteolytic release of L-selectin from
      the cell surface. The effects of the calmodulin inhibitors on L-selectin
      expression and function can be prevented by cotreatment with a hydroxamic acid
      based metalloprotease inhibitor. Our results suggest a novel role for calmodulin
      in regulating the expression and function of an integral membrane protein through
      a protease-dependent mechanism. These findings may have broader implications for
      other cell surface proteins that also undergo regulated proteolysis.

PMID- 9529257
TI  - Cotranslational biogenesis of NF-kappaB p50 by the 26S proteasome.
AB  - The NFkappaB1 gene encodes two functionally distinct proteins termed p50 and
      p105. p50 corresponds to the N terminus of p105 and with p65 (RelA) forms the
      prototypical NF-kappaB transcription factor complex. In contrast, p105 functions
      as a Rel-specific inhibitor (IKB) and has been proposed to be the precursor of
      p50. Our studies now demonstrate that p50 is generated by a unique
      cotranslational processing event involving the 26S proteasome, whereas
      cotranslational folding of sequences near the C terminus of p50 abrogates
      proteasome processing and leads to p105 production. These results indicate that
      p105 is not the precursor of p50 and reveal a novel mechanism of gene regulation
      that ensures the balanced production and independent function of the p50 and p105
      proteins.

PMID- 9529258
TI  - A cold-inducible coactivator of nuclear receptors linked to adaptive
      thermogenesis.
AB  - Adaptive thermogenesis is an important component of energy homeostasis and a
      metabolic defense against obesity. We have cloned a novel transcriptional
      coactivator of nuclear receptors, termed PGC-1, from a brown fat cDNA library.
      PGC-1 mRNA expression is dramatically elevated upon cold exposure of mice in both
      brown fat and skeletal muscle, key thermogenic tissues. PGC-1 greatly increases
      the transcriptional activity of PPARgamma and the thyroid hormone receptor on the
      uncoupling protein (UCP-1) promoter. Ectopic expression of PGC-1 in white adipose
      cells activates expression of UCP-1 and key mitochondrial enzymes of the
      respiratory chain, and increases the cellular content of mitochondrial DNA. These
      results indicate that PGC-1 plays a key role in linking nuclear receptors to the
      transcriptional program of adaptive thermogenesis.

PMID- 9529259
TI  - Conservation of structure and mechanism between eukaryotic topoisomerase I and
      site-specific recombinases.
AB  - Vaccinia DNA topoisomerase breaks and rejoins DNA strands through a DNA-(3'
      phosphotyrosyl)-enzyme intermediate. A C-terminal catalytic domain, Topo(81-314),
      suffices for transesterification chemistry. The domain contains a constellation
      of five amino acids, conserved in all eukaryotic type IB topoisomerases, that
      catalyzes attack of the tyrosine nucleophile on the scissile phosphate. The
      structure of the catalytic domain, consisting of ten alpha helices and a three
      strand beta sheet, resembles the catalytic domains of site-specific recombinases
      that act via a topoisomerase IB-like mechanism. The topoisomerase catalytic
      pentad is conserved in the tertiary structures of the recombinases despite scant
      sequence similarity overall. This implies that the catalytic domains of type IB
      topoisomerases and recombinases derive from a common ancestral strand
      transferase.

PMID- 9529260
TI  - Contribution of tonic chemoreflex activation to sympathetic activity and blood
      pressure in patients with obstructive sleep apnea.
AB  - BACKGROUND: Muscle sympathetic nerve activity (MSNA) is increased in patients
      with obstructive sleep apnea (OSA). We tested the hypothesis that tonic
      activation of excitatory chemoreceptor afferents contributes to the elevated
      sympathetic activity in OSA. METHODS AND RESULTS: Using a double-blind,
      randomized, vehicle-controlled design, we examined the effects of chemoreflex
      deactivation (by comparing effects of breathing 100% oxygen for 15 minutes with
      effects of breathing room air for 15 minutes) on MSNA, heart rate, blood
      pressure, and minute ventilation in 14 untreated patients with OSA and in 12
      normal subjects matched for age and body mass index. All control subjects
      underwent overnight polysomnography to exclude the existence of occult OSA.
      Baseline MSNA was markedly elevated in the patients with OSA compared with the
      control subjects (44+/-4 versus 30+/-3 bursts per minute; P=.01). In both control
      subjects and patients with OSA, heart rate decreased during administration of
      100% oxygen but did not change during administration of room air. By contrast,
      both MSNA (P=.008) and mean arterial pressure (P=.02) were significantly reduced
      during chemoreflex deactivation by 100% oxygen only in patients with OSA but not
      in control subjects. CONCLUSIONS: Tonic activation of excitatory chemoreflex
      afferents may contribute to increased efferent sympathetic activity to muscle
      circulation in patients with OSA.

PMID- 9529261
TI  - Cholesterol reduction yields clinical benefit: impact of statin trials.
AB  - BACKGROUND: We determined the effect of incorporating the results of eight
      recently published trials of Hmg CoA reductase inhibitors ("statins") on the
      conclusions from our previously published meta-analysis regarding the clinical
      benefit of cholesterol lowering. METHODS AND RESULTS: We used the same analytic
      approach as in our previous investigation, separating the specific effects of
      cholesterol lowering from the effects attributable to the different types of
      intervention studied. The reductions in coronary heart disease (CHD) and total
      mortality risk observed for the statins fell near the predictions from our
      earlier meta-analysis. Including the statin trial findings into the calculations
      led to a prediction that for every 10 percentage points of cholesterol lowering,
      CHD mortality risk would be reduced by 15% (P<.001), and total mortality risk
      would be reduced by 11% (P<.001), as opposed to the values of 13% and 10%,
      respectively, reported previously. Cholesterol lowering in general and by the
      statins in particular does not increase non-CHD mortality risk. CONCLUSIONS:
      Adding the results from the statin trials confirmed our original conclusion that
      lowering cholesterol is clinically beneficial. The relationships (slope) between
      cholesterol lowering and reduction in CHD and total mortality risk became
      stronger, and the standard error of the estimated slopes decreased by about half.
      Use of statins does not increase non-CHD mortality risk. The effect of the
      statins on CHD and total mortality risk can be explained by their lipid-lowering
      ability and appears to be directly proportional to the degree to which they lower
      lipids.

PMID- 9529262
TI  - Increased levels of soluble P-selectin in hypercholesterolemic patients.
AB  - BACKGROUND: Hypercholesterolemia is considered a major risk factor for the
      development of atherosclerosis. Enhanced lipid peroxidation and persistent
      platelet activation can be observed in vivo in hypercholesterolemic patients and
      may have pathophysiological implications in the occurrence of cardiovascular
      events. P-selectin may play an important role in the pathogenesis of
      multicellular events, including atherosclerosis. We studied the impact of
      hypercholesterolemia and oxidative stress on plasma levels of P-selectin. METHODS
      AND RESULTS: Plasma levels of P-selectin were measured by means of an enzyme
      immunoassay in 20 hypercholesterolemic patients with no clinical evidence of
      cardiovascular disease and in 20 sex- and age-matched normocholesterolemic
      subjects. Hypercholesterolemic patients had higher levels of P-selectin compared
      with that of control subjects (98+/-61 versus 56+/-14 ng/mL; P=.001). They also
      displayed increased von Willebrand Factor (vWF) levels (176+/-22 versus 119+/
      12%; P=.0001). A direct correlation was observed between P-selectin and LDL
      cholesterol levels (p=.453). Administration of vitamin E (600 mg/d for 2 weeks)
      to hypercholesterolemic patients significantly reduced plasma P-selectin (40%),
      and an inverse correlation was observed between vitamin E and P-selectin plasma
      levels (p=-.446). CONCLUSIONS: Hypercholesterolemia is associated with elevated
      plasmatic P-selectin. Altered oxidative processes leading to endothelial
      dysfunction and persistent platelet activation may contribute to increased
      soluble P-selectin levels. P-selectin may be proposed as a marker of endothelial
      dysfunction in hypercholesterolemic patients.

PMID- 9529263
TI  - Prognostic importance of emotional support for elderly patients hospitalized with
      heart failure.
AB  - BACKGROUND: Several studies have indicated that a variety of social relationships
      are important predictors of morbidity and mortality in patients with coronary
      artery disease, but little attention has been focused on the prognostic
      importance of these factors in the growing population of elderly patients with
      heart failure. To address this issue, we sought to determine whether emotional
      support is associated with fatal and nonfatal cardiovascular events in elderly
      patients hospitalized with heart failure. METHODS AND RESULTS: We reviewed the
      medical records of 292 subjects aged > or =65 years who were hospitalized with
      clinical heart failure and were part of the New Haven, Conn, cohort of the
      Established Population for the Epidemiologic Study of the Elderly, a
      longitudinal, community-based study of aging that included a comprehensive
      assessment of psychosocial support. In the unadjusted analysis, lack of emotional
      support was significantly associated with the 1-year risk of fatal and nonfatal
      cardiovascular outcomes [odds ratio, 2.4; 95% confidence interval, 1.1 to 4.9].
      After adjustment for demographic factors, clinical severity, comorbidity and
      functional status, social ties, and instrumental support, the absence of
      emotional support remained associated with a significantly higher risk (odds
      ratio, 3.2; 95% confidence interval, 1.4 to 7.8). The test for interaction
      between emotional support and sex was significant (P=.01). In the fully adjusted
      model, the odds ratio for women was 8.2 (95% confidence interval, 2.5 to 27.2)
      compared with 1.0 (95% confidence interval, 0.3 to 3.3) for men. CONCLUSIONS:
      Among elderly patients hospitalized with clinical heart failure, the absence of
      emotional support, measured before admission, is a strong, independent predictor
      of the occurrence of fatal and nonfatal cardiovascular events in the year after
      admission. In this cohort, the association is restricted to women.

PMID- 9529264
TI  - Significance of paroxysmal atrial fibrillation complicating acute myocardial
      infarction in the thrombolytic era. SPRINT and Thrombolytic Survey Groups.
AB  - BACKGROUND: Paroxysmal atrial fibrillation (PAF) is considered a frequent
      complication of acute myocardial infarction (AMI), associated with increased in
      hospital and long-term mortality rates. This notion is based on data collected
      before thrombolysis and additional modern methods of treatment became widely
      available, and no information is available on the significance of PAF in the
      general population with AMI in the thrombolytic era. The aim of the present study
      was to define the incidence, associated clinical parameters, and short- and long
      term prognostic significance of PAF in patients with AMI in the thrombolytic era.
      METHODS AND RESULTS: A prospective, nationwide survey was conducted of 2866
      consecutive patients admitted with AMI in all 25 coronary care units in Israel
      during January/February 1992, 1994, and 1996 (thrombolytic era [TE]). The data
      were compared with a previous Israeli study of 5803 patients with AMI
      hospitalized in 1981 through 1983 (prethrombolytic era [PTE]). Patients in the TE
      with PAF were older and had a worse risk profile than those without PAF. PAF in
      the TE was independently associated with increased 30-day (odds ratio, 1.32; 95%
      confidence interval, 0.92 to 1.87) and 1-year (relative risk, 1.33; 95%
      confidence interval, 1.05 to 1.68) mortality rates. The incidence of PAF (8.9%
      and 9.9%) and the 30-day (25.1% and 27.6%) and 1-year (38.4% and 42.5%) mortality
      rates of patients with PAF were similar in the TE and PTE, although PAF in the TE
      occurred in older and sicker patients than those in the PTE. After adjustment for
      conventional risk factors, PAF was associated with significantly lower 30-day
      (odds ratio, 0.64; 95% confidence interval, 0.44 to 0.94) and 1-year (relative
      risk, 0.69; 95% confidence interval, 0.54 to 0.88) mortality rates compared with
      the PTE. CONCLUSIONS: Patients with AMI who develop PAF in the TE have
      significantly worse short- and long-term prognoses than patients without PAF,
      mostly due to their worse risk profile. After adjustment for confounding factors,
      patients with PAF in the TE have a better overall outcome than counterparts in
      the PTE, probably reflecting the better management of patients with AMI in the
      TE.

PMID- 9529265
TI  - Stem cell factor in mast cells and increased mast cell density in idiopathic and
      ischemic cardiomyopathy.
AB  - BACKGROUND: We compared cardiac mast cell (HHMC) density and the immunological
      and nonimmunological release of mediators from mast cells isolated from heart
      tissue of patients with idiopathic dilated (DCM) (n=24) and ischemic
      cardiomyopathy (ICM) (n = 10) undergoing heart transplantation and from control
      subjects (n = 10) without cardiovascular disease. METHODS AND RESULTS: HHMC
      density in DCM (18.4+/-1.6 cells/mm2) and ICM (18.4+/-1.5 cells/mm2) was higher
      than that in control hearts (5.3+/-0.7 cells/mm2; P<.01). The histamine and
      tryptase contents of DCM and ICM hearts were higher than those of control hearts.
      The histamine content of the hearts was correlated with mast cell density
      (r(s)=.91; P<.001). Protein A/gold staining of heart tissue revealed stem cell
      factor (SCF), the principal growth, differentiating, and activating factor of
      human mast cells, in HHMC secretory granules. Histamine release from cardiac mast
      cells caused by immunological (anti-IgE and rhSCF) and nonimmunological stimuli
      (Ca2+ ionophore A23187) was higher in patients with DCM and ICM compared with
      control subjects. Immunological activation of HHMC induced a significantly
      greater release of tryptase and LTC4 in patients with DCM and ICM compared with
      control subjects. CONCLUSIONS: Histamine and tryptase content and mast cell
      density are higher in failing hearts than in control hearts. SCF, present in
      secretory granules of HHMC, might represent an autocrine factor sustaining mast
      cell hyperplasia in heart tissue in these patients. The increased local release
      of fibrogenic factors (eg, histamine, tryptase, and leukotriene C4) might
      contribute to collagen accumulation in the hearts of patients with
      cardiomyopathy.

PMID- 9529266
TI  - Effect of postmenopausal hormone therapy on lipoprotein(a) concentration. PEPI
      Investigators. Postmenopausal Estrogen/Progestin Interventions.
AB  - BACKGROUND: Postmenopausal hormone therapy has been reported to decrease levels
      of lipoprotein (Lp)(a) in cross-sectional studies and small or short-term
      longitudinal studies. We report findings from a large, prospective, placebo
      controlled clinical trial that allows a broad characterization of these effects
      for four regimens of hormone therapy. METHODS AND RESULT: The Postmenopausal
      Estrogen/Progestin Interventions study was a 3-year, placebo-controlled,
      randomized clinical trial to assess the effect of hormone regimens on
      cardiovascular disease risk factors in postmenopausal women 45 to 65 years of
      age. The active regimens were conjugated equine estrogens therapy at 0.625 mg
      daily, alone or in combination with each of three regimens of progestational
      agents: medroxyprogesterone acetate (MPA) at 2.5 mg daily (ie, continuous MPA),
      MPA at 10 mg days 1 to 12 (ie, cyclical MPA), and micronized progesterone at 200
      mg days 1 to 12. Plasma levels of Lp(a) were measured at baseline (n = 366), 12
      months (n = 354), and 36 months (n = 342). Assignment to hormone therapy resulted
      in a 17% to 23% average drop in Lp(a) concentrations relative to placebo
      (P<.0001), which was maintained across 3 years of follow-up. No significant
      differences were observed among the four active arms. Changes in Lp(a) associated
      with hormone therapy were positively correlated with changes in LDL cholesterol,
      total cholesterol, apolipoprotein B, and fibrinogen levels and were similar
      across subgroups defined by age, weight, ethnicity, and prior hormone use.
      CONCLUSIONS: Postmenopausal estrogen therapy, with or without concomitant
      progestin regimens, produces consistent and sustained reductions in plasma Lp(a)
      concentrations.

PMID- 9529267
TI  - Heart failure and echocardiographic changes during long-term follow-up of
      patients with sick sinus syndrome randomized to single-chamber atrial or
      ventricular pacing.
AB  - BACKGROUND: In patients with sick sinus syndrome, choice of pacing mode has been
      implicated in the development of congestive heart failure. METHODS AND RESULTS: A
      total of 225 consecutive patients with sick sinus syndrome and intact
      atrioventricular conduction were randomized to either single-chamber atrial
      pacing (n = 110) or single-chamber ventricular pacing (n = 115). Clinical
      assessment included New York Heart Association classification, medication, and M
      mode echocardiography before pacemaker implantation, after 3 months, and
      subsequently once every year. At long-term follow-up (mean, 5.5+/-2.4 years),
      NYHA class was higher in the ventricular group than in the atrial group (NYHA
      class I/II/III/IV: 65/44/4/0 versus 84/22/2/1 patients, P=.010). Increase in NYHA
      class during follow-up was observed in 35 of 113 patients in the ventricular
      group versus 10 of 109 in the atrial group (P<.0005). Increase in dose of
      diuretics from randomization to last follow-up was significantly higher in the
      ventricular group than in the atrial group (21+/-49 versus 8+/-42 mg
      furosemide/d, P=.033). The left ventricular fractional shortening decreased
      significantly in the ventricular group (from 0.36+/-0.12 to 0.31+/-0.08, P<.0005)
      but not in the atrial group (from 0.35+/-0.13 to 0.33+/-0.09, P=.087). The left
      atrial diameter increased significantly in both treatment groups (ventricular
      group: from 34+/-7 to 41+/-7 mm, P<.0005; atrial group: from 34+/-6 to 37+/-7 mm,
      P=.002), but the increase was significantly higher in the ventricular group than
      in the atrial group (P<.0005). CONCLUSIONS: During long-term follow-up,
      ventricular pacing is associated with a higher incidence of congestive heart
      failure and consumption of diuretics than atrial pacing. This is accompanied by a
      decrease in left ventricular fractional shortening and an increased dilatation of
      the left atrium in the ventricular paced patients.

PMID- 9529268
TI  - Insulin and risk of cardiovascular disease: a meta-analysis.
AB  - BACKGROUND: Our purposes were to estimate the strength of the longitudinal
      relationship between hyperinsulinemia and cardiovascular diseases (CVD) from the
      available literature and to identify study characteristics that modify this
      relationship. METHODS AND RESULTS: Articles were identified by means of a MEDLINE
      and Embase search and citation tracking. Eligible studies were prospective
      population-based cohort studies and nested case-control studies on the
      relationship between, on the one hand, fasting or nonfasting insulin levels and,
      on the other hand, myocardial infarction, death from coronary heart disease,
      and/or ECG abnormalities. Data were extracted pertaining to insulin measurements,
      type of outcome studied, adjustment for confounding, sex, mean age of the study
      population, follow-up period, insulin assay, and ethnic background (white or
      nonwhite). Associations of insulin and CVD were reexpressed in a uniform manner,
      an estimate of relative risk (RR) and 95% CI, to be used in meta-regression
      analyses. Twelve of 17 potentially eligible articles provided sufficient
      information. Overall, a weak positive association was found. The meta-analysis
      resulted in an estimated summary RR (95% CI) of 1.18 (1.08 to 1.29) for
      differences in insulin level, equivalent to the difference between the 75th and
      the 25th percentiles of the general population in The Netherlands. Ethnic
      background and type of insulin assay modified the relationship between insulin
      and CVD with borderline significance. CONCLUSIONS: Hyperinsulinemia is a weak
      risk indicator for the occurrence of CVD. The relationship between
      hyperinsulinemia and CVD was modified by ethnic background and by the type of
      insulin assay involved.

PMID- 9529269
TI  - Regulation of arterial thrombolysis by plasminogen activator inhibitor-1 in mice.
AB  - BACKGROUND: Platelet-rich arterial thrombi are resistant to lysis by plasminogen
      activators. However, the mechanisms underlying thrombolysis resistance are poorly
      defined. Plasminogen activator inhibitor-1 (PAI-1), which is present in plasma,
      platelets, and vascular endothelium, may be an important determinant of the
      resistance of arterial thrombi to lysis. However, in vitro studies examining the
      regulation of platelet-rich clot lysis by PAI-1 have yielded inconsistent
      results. METHODS AND RESULTS: We developed a murine arterial injury model and
      applied it to wild-type (PAI-1 [+/+]) and PAI-1-deficient (PAI-1 [-/-]) animals.
      FeCl3 was used to induce carotid artery thrombosis. Thrombi consisted
      predominantly of dense platelet aggregates, consistent with the histology of
      thrombi in large-animal arterial injury models and human acute coronary
      syndromes. To examine the role of PAI-1 in regulating endogenous clearance of
      platelet-rich arterial thrombi, thrombi were induced in 22 PAI-1 (+/+) mice 14
      PAI-1 (-/-) mice. Twenty-four hours later, the amount of residual thrombus was
      determined by histological analysis of multiple transverse sections of each
      artery. Residual thrombus was detected in 55 of 85 sections (64.7%) obtained from
      PAI-1 (+/+) mice compared with 19 of 56 sections (33.9%) from PAI-1 (-/-) mice
      (P=.009). Computer-assisted planimetry analysis revealed that mean thrombus cross
      sectional area was 0.033+/-0.0271 mm2 in PAI-1 (+/+) mice versus 0.016+/-0.015
      mm2 in PAI-1 (-/-) mice (P=.048). CONCLUSIONS: PAI-1 is an important determinant
      of thrombolysis at sites of arterial injury. Application of this model to other
      genetically altered mice should prove useful for studying the molecular
      determinants of arterial thrombosis and thrombolysis.

PMID- 9529270
TI  - Positron emission tomography analysis of [1-(11)C] acetate kinetics in short-term
      hibernating myocardium.
AB  - BACKGROUND: Modeling of the time-[1-(11)C]acetate activity curve assumes a
      constant concentration of labeled tricarboxylic acid cycle intermediates and
      associated metabolites, such as glutamate and aspartate, which may, however,
      decrease in short-term hibernating myocardium. METHODS AND RESULTS: In 12
      anesthetized pigs, [1-(11)C]acetate was injected as a bolus into the cannulated
      left anterior descending coronary artery during normoperfusion, inotropic
      stimulation, and early (5 to 45 minutes) and prolonged ischemia (60 to 90
      minutes). Regional myocardial oxygen consumption (MVO2, microliters per minute
      per gram) was measured, and the absence of necrosis was verified by triphenyl
      tetrazolium chloride staining. Inotropic stimulation increased MVO2 from 52.5+/
      7.4 to 195.4+/-36.2 (mean+/-SD) and the rate constant (kmono, minutes[-1]) of [1
      (11)C]acetate clearance from 0.094+/-0.018 to 0.322+/-0.076. During early
      ischemia, MVO2 and kmono were decreased to 24.3+/-8.5 and 0.061+/-0.011,
      respectively. Kmono closely correlated to MVO2 during normoperfusion, inotropic
      stimulation, and early ischemia. In short-term hibernating myocardium, however,
      at an unchanged MVO2, kmono increased toward control values (0.080+/-0.014).
      Myocardial glutamate and aspartate concentrations (biopsies) decreased to 47+/
      26% and 77+/-18%; the peak count rate decreased to 66+/-22% of its respective
      control value. After correction for the decreases in glutamate and aspartate or
      in peak count rate, kmono was again decreased (0.050+/-0.016 or 0.052+/-0.014,
      respectively), and a close relationship to MVO2 was restored. CONCLUSIONS: Kmono
      correlates to MVO2 in short-term hibernating myocardium when the decreases in
      aspartate and glutamate or in peak count rate are considered.

PMID- 9529271
TI  - Effects of intranasal administration of recombinant murine interferon-gamma on
      murine acute myocarditis caused by encephalomyocarditis virus.
AB  - BACKGROUND: Viral myocarditis has been strongly implicated in the pathogenesis of
      dilated cardiomyopathy as well as acute myocarditis. Among the antiviral
      therapies, interferons (IFNs) have been widely studied and become very important
      in clinical practice. METHODS AND RESULTS: To investigate the possibilities of
      IFN therapy in viral myocarditis, we analyzed the effects of recombinant murine
      interferon (mIFN)-gamma and natural mIFN-alpha/beta by the intranasal and
      intramuscular routes on the development of acute murine myocarditis caused by
      encephalomyocarditis virus. Both mIFN-gamma and mIFN-alpha/beta treatment by
      either route significantly increased the survival rate; none of the mIFN-gamma
      treated mice died. The effect of mIFN-gamma was significantly greater than that
      of mIFN-alpha/beta. Furthermore, intranasal administration of mIFN-gamma
      significantly suppressed virus replication and inflammation in the heart.
      CONCLUSIONS: Our data demonstrate that IFN therapy, especially intranasal
      administration of IFN-gamma, dramatically improved the prognosis of acute murine
      viral myocarditis by suppressing virus replication and raises the possibility of
      antiviral therapy with IFN-gamma in patients with acute myocarditis.

PMID- 9529272
TI  - Images in cardiovascular medicine. Use of magnetic resonance imaging to
      demonstrate a fistula from the aorta to the right atrium.

PMID- 9529273
TI  - Images in cardiovascular medicine. Loffler's endocarditis.

PMID- 9529274
TI  - If that is the left ureter, where is the left kidney?

PMID- 9529275
TI  - Pediatric nuclear medicine: special issues, unique clinical studies.

PMID- 9529276
TI  - Nuclear medicine pioneer: Hal O. Anger. First scintillation camera is foundation
      for modern imaging systems.

PMID- 9529277
TI  - Future of nuclear medicine, part 2: assessment of the U.S. diagnostic radio
      pharmaceuticals market (2001-2020)

PMID- 9529278
TI  - Effect of hyperinsulinemia on myocardial fluorine-18-FDG uptake.
AB  - This study was performed to evaluate the effect of insulin on myocardial kinetics
      of 18F-fluorodeoxyglucose (FDG) and glucose in patients with ischemic heart
      disease. METHODS: Twelve male patients (age range 54-79 yr; mean age 69 +/- 8 yr)
      were studied during the fasting awake state. Patients with diabetes and previous
      myocardial infarction of the left anterior descending vascular bed were excluded
      from the study. Patients were injected with a 185-MBq (5-mCi) bolus of FDG during
      arterial and coronary sinus catheterization. Thirty minutes after FDG injection,
      paired basal arterial and coronary sinus blood samples were taken for the
      measurement of FDG and glucose uptake. Thereafter, a primed (100 mU x m(-2) x
      min(-1) for 10 min) continuous (50 mU x m(-2) x min(-1) infusion of insulin was
      administered for 60 min using the euglycemic clamp technique, and blood samples
      were repeated. Blood samples also were taken periodically for the measurement of
      arterial free fatty acids and insulin. RESULTS: Euglycemic insulin infusion
      lowered arterial concentrations of free fatty acids, reducing myocardial
      extraction of free fatty acids by 85% and stimulated uptake of glucose and FDG.
      Myocardial glucose and FDG extraction fractions (%) increased from 1 +/- 1 and 2
      +/- 2 at baseline to 8 +/- 2 and 10 +/- 3 during insulin infusion, respectively.
      The lumped constant value was estimated to be 1.44 +/- 0.14 (r = 0.87) for the
      fasted state, 0.99 +/- 0.07 (r = 0.74) during insulin infusion and 1.00 +/- 0.05
      (r = 0.92) when both groups of data were pooled together. CONCLUSION: The data
      obtained in this study show that FDG uptake quantitatively traces glucose uptake
      during physiological hyperinsulinemia in patients with ischemic heart disease.

PMID- 9529279
TI  - Rest-redistribution thallium-201 SPECT to detect myocardial viability.
AB  - Rest-redistribution 201Tl imaging is currently being used for myocardial
      viability detection, but the ideal parameters for territory classification have
      not yet been defined. The aim of this study was to define the optimal criteria
      for detecting viable myocardium and predicting postrevascularization recovery
      with rest-redistribution 201Tl SPECT. METHODS: In 29 patients with left
      ventricular dysfunction, tracer activity within asynergic segments was quantified
      on rest and redistribution 201Tl SPECT. Viability was defined by the presence of
      functional recovery, which was detected by comparing wall motion in baseline and
      follow-up echocardiography. Discriminant function analysis and receiver operating
      characteristic (ROC) curve analysis were used to evaluate the relationship
      between 201Tl data and viability. RESULTS: Of 214 dysfunctioning segments (135 a
      /dyskinetic), viability was demonstrated in 115 (75 a-/dyskinetic). Both rest and
      redistribution 201Tl activity in these segments were significantly higher than
      they were in the nonviable segments (p < 0.0001). Significant (> 10%)
      reversibility was observed in 39% of the viable and in 36% of the nonviable
      segments (p = 0.81). Discriminant analysis identified redistribution activity,
      followed by rest activity, as the most effective predictors of functional
      recovery. Similar areas were found under the ROC curve for rest (0.68 +/- 0.037)
      and for redistribution activity (0.70 +/- 0.036) (p = 0.13). ROC curve analysis
      identified the optimal cutoff for redistribution activity at < 60%, with 147 of
      214 (69%) segments correctly classified (sensitivity = 78% and specificity =
      58%). In the subset of a-/dyskinetic segments, redistribution activity presented
      a significantly larger ROC curve area (0.81 +/- 0.038 compared to 0.77 +/- 0.042,
      p < 0.05), and 103 of 135 (76%) segments were correctly classified (sensitivity =
      81% and specificity = 70%). CONCLUSION: Redistribution activity is the most
      important parameter to be considered in rest-redistribution 201Tl to
      differentiate viable from nonviable segments; rest activity is also valuable,
      whereas the meaning of reversibility appears limited. Cutoff values about 60%
      appear to give the most reasonable balance between sensitivity and specificity.

PMID- 9529280
TI  - Impairment of BMIPP uptake precedes abnormalities in oxygen and glucose
      metabolism in hypertrophic cardiomyopathy.
AB  - Impairment of fatty acid uptake is shown to precede myocardial perfusion
      abnormality using 123I-labeled 15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid
      (BMIPP) in an experimental model of hypertrophic cardiomyopathy (HCM) and in
      human studies. We have recently demonstrated that abnormalities of both glucose
      and oxidative metabolism precede the reduction of blood flow in HCM. The main
      purposes of this study were to assess the frequency of abnormal findings in FDG
      uptake, BMIPP uptake and oxygen metabolism and to clarify the relationship among
      these metabolic parameters by using PET and SPECT. METHODS: Twenty-eight subjects
      with HCM underwent FDG- and acetate-PET and thallium- and BMIPP-SPECT studies at
      rest, respectively. After correcting for partial volume effect, real percentages
      of FDG and BMIPP uptake were calculated. In addition, the clearance rate constant
      (K mono) of acetate was measured and normalized (%) to estimate the oxygen
      metabolism. RESULTS: There were various metabolic abnormalities observed in
      patients with HCM. BMIPP uptake was often impaired without significant reduction
      of K mono values or FDG uptake. Thus, abnormality of BMIPP uptake was more
      frequently observed than that for FDG uptake or K mono values (p < 0.0001,
      respectively). FDG uptake was relatively maintained even in the segments with
      reduced K mono values and reduced BMIPP uptake. CONCLUSION: HCM shows a variety
      of metabolic patterns; however, the results of our study suggest that reduction
      of BMIPP uptake appears to be the most sensitive indicator of metabolic
      abnormalities followed by reduction of oxidative metabolism in patients with HCM.

PMID- 9529281
TI  - Perfusion-contraction mismatch during inotropic stimulation in hibernating
      myocardium.
AB  - The aims of this study were to assess the value of dobutamine echocardiography in
      identifying myocardial hibernation versus stunning and to elucidate the
      underlying pathophysiological mechanism of the contractile impairment. METHODS:
      Twenty-one patients with isolated stenosis of the left anterior descending artery
      were evaluated 1 mo after thrombolysed acute anterior infarction. Regional
      function and blood flow were measured using echocardiography and PET at rest and
      during dobutamine administration (10 microg/kg/min). RESULTS: Defined by
      [18F]fluorodeoxyglucose uptake, 36 of 102 dyssynergic segments were necrotic, and
      66 were viable. The latter segments were subdivided according to their
      [13N]ammonia flow distribution: 30 hibernating regions with perfusion defects
      (flow of <80% of maximum) and 36 stunned areas with preserved resting perfusion
      (flow of > or =80% of maximum). Resting flows were similar in necrosis and
      hibernation (0.43 +/- 0.18 versus 0.47 +/- 0.16 ml x min(-1) x g(-1); not
      significant), and both resting values were lower than those seen in stunning
      (0.79 +/- 0.24; p < 0.05). Flow response to dobutamine was markedly reduced in
      necrosis (dobutamine/resting flow = 1.16 +/- 0.27), whereas it was maintained in
      hibernation (1.65 +/- 0.54) and stunning (1.42 +/- 0.57). Dobutamine improved
      function in a higher number of stunned (55%) than hibernating (16%) or necrotic
      (11%) segments. CONCLUSION: Dobutamine improves function mainly in stunned
      myocardium and does not reliably identify hibernation. The lack of functional
      response in hibernation is not related to an exhausted vasodilating capacity.

PMID- 9529282
TI  - Quantitative assessment of transient regional ischemia during rotational
      atherectomy.
AB  - Sustained myocardial ischemia with angina pectoris, electrocardiographic changes
      and subsequent non-Q-wave infarctions has been reported during percutaneous
      transluminal rotational atherectomy of complex coronary lesions. The purpose of
      this study was to evaluate the effect of rotational atherectomy on regional
      myocardial perfusion as assessed by serial 99mTc-sestamibi SPECT imaging with
      semiquantitative tracer uptake analysis. METHODS: Twenty-nine consecutive
      patients with anginal symptoms, complex coronary lesions (all Type B and Type C)
      and preserved left ventricular function were studied using resting 99mTc
      sestamibi SPECT before rotational atherectomy, during and 2 days after the
      procedure. For semiquantitative computerized analysis, the left ventricular
      myocardium was divided into 24 regions, and regional perfusion was expressed as
      percentage of maximal sestamibi uptake. RESULTS: Visual analysis of scintigraphic
      images revealed transient perfusion defects corresponding to the revascularized
      vessel in 26 of 29 patients, whereas three patients had no transient
      hypoperfusion. During rotational atherectomy, perfusion decreased significantly
      (>2 s.d. below normal mean) in 3.1 +/- 2.4 regions (range 1-10). Perfusion in the
      territory of the revascularized vessel was 75% +/- 11% at baseline, decreased to
      67% +/- 12% during rotational atherectomy (p < 0.001) and normalized again after
      rotational atherectomy to 78% +/- 8% (p < 0.001). Similarly, perfusion in the
      region with the maximal reduction decreased from 74% +/- 15% at baseline to 55%
      +/- 14% (p < 0.001) during the procedure and returned to 74% +/- 16% (p < 0.001)
      following the intervention. In calcified stenoses, the extent of perfusion
      defects was larger as compared to noncalcified (4.2 +/- 2.5 versus 2.3 +/- 2.0
      regions/patient, p < 0.05). CONCLUSION: During rotational atherectomy, myocardial
      hypoperfusion occurs. The transient nature of this perfusion defect can be
      demonstrated and quantified by serial 99mTc SPECT. This model may prove useful to
      assess the effects of pharmacological approaches to reducing myocardial
      hypoperfusion during coronary rotational atherectomy.

PMID- 9529283
TI  - Combined thallium-201 myocardial with technetium-99m-HMPAO brain SPECT:
      myocardial ischemia induced by acetazolamide in severe coronary artery disease.
AB  - Since the perioperative mortality of coronary artery bypass surgery is high in
      patients with cerebrovascular disease, it is crucial to assess a cerebrovascular
      risk before operation. Acetazolamide (ACZ) was applied to brain SPECT to evaluate
      the vascular reserve, and ACZ stress brain imaging was useful for predicting
      perioperative cerebrovascular events. We performed 201Tl myocardial and 99mTc
      hexamethyl-propyleneamine oxime (HMPAO) brain SPECT with ACZ stress
      simultaneously to a patient with severe coronary artery disease and experienced
      the abnormality of 201Tl myocardial imaging with ACZ, as did that with
      dipyridamole. Technetium-99m-HMPAO brain SPECT showed no defect. Brain SPECT with
      ACZ demonstrated the region of poor coronary vascular reserve, which suggested
      myocardial ischemia induced by ACZ in a patient with severe coronary artery
      disease.

PMID- 9529284
TI  - Effects of misalignment between transmission and emission scans on attenuation
      corrected cardiac SPECT.
AB  - Misalignment between transmission and emission scans in attenuation-corrected
      (AC) cardiac SPECT can introduce errors of measured activity. The severity of
      these errors, however, has not yet been fully elucidated. METHODS: We performed a
      phantom measurement as well as a study of patients with low likelihood of
      coronary artery disease. Transmission and emission scans were acquired using a
      triple-head SPECT system with a collimated 241Am line source and an offset
      fanbeam collimator. The left ventricular myocardium was divided into five
      segments, and the mean regional activity was calculated for each segment using a
      semiquantitative polar map approach. Misalignment between transmission and
      emission data was created by shifting the emission data along the x, y or z axis.
      RESULTS: In the heart phantom, a shift between the transmission and emission data
      produced a decrease or increase in relative regional activity in each segment
      resulting in heterogeneous activity distribution. A 7-mm (1-pixel) shift produced
      up to 15% change in relative regional activity, suggesting that even a small
      misalignment between transmission and emission data can produce serious errors in
      measured activity. In the clinical data, the effects of misalignment were less
      significant than those observed in the phantom data but were still measurable and
      visually identifiable. CONCLUSION: The results indicate that a small misalignment
      between the transmission and emission data can produce serious errors in measured
      activity, and, thus, geometrical precision is essential for accurate diagnosis of
      AC SPECT images.

PMID- 9529285
TI  - Limitations of dobutamine for enhancing flow heterogeneity in the presence of
      single coronary stenosis: implications for technetium-99m-sestamibi imaging.
AB  - Dobutamine is used as an alternative to exercise in conjunction with 99mTc
      sestamibi SPECT perfusion imaging for detection of coronary artery disease.
      However, the use of quantitative dobutamine 99mTc-sestamibi SPECT imaging for
      enhanced detection of coronary stenosis has not been established. The goal of
      this study is to examine the effects of dobutamine stress on regional myocardial
      blood flow and relative myocardial 99mTc-sestamibi activity in the presence of a
      single-vessel stenosis. METHODS: In six open-chest dogs with left circumflex
      artery stenosis, radiolabeled microspheres were injected during baseline, severe
      stenosis and peak dobutamine stress (10 microg/kg/min). Technetium-99m-sestamibi
      was injected intravenously at peak dobutamine. Hearts were excised 20 min after
      99mTc-sestamibi injection for SPECT imaging and post-mortem gamma-well counting.
      RESULTS: Dobutamine significantly increased heart rate, rate-pressure product and
      the first derivative of left ventricular pressure. Ischemic zone (left
      circumflex) myocardial blood flows (in ml/min/g) were: baseline, 0.92 +/- 0.15;
      stenosis, 0.65 +/- 0.16; and dobutamine, 1.19 +/- 0.38. Nonischemic zone
      myocardial blood flows were: baseline, 0.99 +/- 0.18; stenosis, 1.01 +/- 0.12;
      and dobutamine, 1.94 +/- 0.32 (p < 0.01 versus stenosis). Ischemic flows,
      expressed as percentages of nonischemic flows, were: baseline, 94% +/- 2%;
      stenosis, 63% +/- 11% (p < 0.05 versus baseline) and dobutamine, 60% +/- 12% (p
      was not significant versus stenosis). Technetium-99m-sestamibi activity in the
      ischemic zone (75% +/- 6% nonischemic) underestimated the relative flow deficit
      produced during dobutamine stress (p = 0.056). Myocardial 99mTc-sestamibi
      activity correlated with flow when flow was less than 1.0 ml/min/g. At higher
      flow ranges (1.0 ml/min/g-3.5 ml/min/g), 99mTc-sestamibi did not track flow.
      CONCLUSION: In a canine model of flow-limiting, single-vessel stenosis,
      dobutamine (10 microg/kg/min) did not augment flow heterogeneity. In addition,
      relative myocardial 99mTc-sestamibi activity underestimated microsphere flow at
      higher flows induced by dobutamine, leading to underestimation of ischemia. These
      findings suggest that dobutamine stress 99mTc-sestamibi scintigraphy may
      underestimate the relative flow deficit.

PMID- 9529286
TI  - Use of significance image to determine patterns of cortical blood flow
      abnormality in pathological and at-risk groups.
AB  - The purpose of this work was to determine whether certain pathological groups and
      other groups at risk for neurological damage exhibited distinctive patterns of
      regional cerebral blood flow (rCBF) abnormality. METHODS: HMPAO SPECT images
      obtained from six groups of subjects were compared with a normal cortical rCBF
      atlas, based on multivariate, voxel-by-voxel methods. In each case, a
      significance image was outputted, highlighting voxels with deficits of > or =3
      s.d. of normal. Abnormal patterns were examined for the six groups, which
      comprised a further 40 normal volunteers, 18 diver controls, 50 divers with
      decompression illness (DCI), 34 boxers, 23 schizophrenics and 21 subjects with
      Alzheimer's disease. RESULTS: The percentages of abnormal cortical voxels for
      each group were 0.41%, 0.53%, 1.38%, 1.05%, 0.56% and 2.24%, respectively. The
      percentages of images in each group with at least one lesion of 10 or more
      connected abnormal voxels and at least 10 lesions of two or more connected
      voxels, respectively, were 8% and 8% (normal volunteers), 17% and 11% (diver
      controls), 38% and 38% (divers with DCI), 41% and 29% (boxers), 26% and 13%
      (schizophrenics) and 90% and 48% (subjects with Alzheimer's disease). This
      suggests that multiple small lesions are as common as single large lesions for
      divers with DCI but not for patients with Alzheimer's disease or schizophrenia.
      Large lesions are located predominantly in the parietal and inferior temporal
      regions for Alzheimer's disease, in the parietal and occipital regions for divers
      with DCI and boxers and in the inferior frontal region for schizophrenia.
      CONCLUSION: It appears that the groups considered here do have different rCBF
      patterns and that the significance image is a useful way of demonstrating this
      fact.

PMID- 9529287
TI  - Accuracy of whole-body fluorine-18-FDG PET for the detection of recurrent or
      metastatic breast carcinoma.
AB  - This study assessed the diagnostic accuracy of whole-body PET on a patient and
      lesion basis using 18F-fluorodeoxyglucose (FDG) for the detection of tumor foci
      in patients with suspected recurrent or metastatic lesions of breast carcinoma.
      METHODS: Whole-body FDG-PET imaging was performed on 57 patients with a previous
      history of breast carcinoma who were referred for a clinical suspicion of disease
      recurrence. Whole-body PET images were scored from 1 (definitely negative) to 5
      (definitely positive) by three independent observers, and discrepancies were
      resolved by a fourth observer. Patients were clinically followed for up to 24 mo
      to assess the accuracy of PET diagnosis by biopsy, follow-up imaging and other
      diagnostic tests. RESULTS: PET scans showed that there were 41 sites indicating
      recurrent or metastatic disease in 29 patients. There were 38 sites in 28
      patients that showed no evidence for malignant disease. On a patient basis, with
      scores 4 or 5 considered to be positive, sensitivity and specificity were 93% and
      79%, respectively. The corresponding positive and negative predictive values were
      82% and 92%. On a lesion basis, with scores 4 or 5 considered to be positive, the
      sensitivity was 85% and specificity 79%. The area index in receiver operating
      characteristic analysis was 0.91 for patient-based analysis and 0.88 for lesion
      based analysis. To determine the cause for false-negative and false-positive
      findings more precisely, false-negative lesions with scores of 3 or lower and
      false-positive lesions with scores of 4 or higher were analyzed. Bone metastases
      had a significantly larger proportion of false-negative lesions than other
      nonosseous malignant sites (p < 0.05). False-positive lesions were due to muscle
      uptake (n = 5), inflammation (n = 4), blood pool activity in the great vessels (n
      = 2), bowel uptake (n = 1) and unknown causes (n = 6). CONCLUSION: The whole-body
      FDG-PET scan is a useful diagnostic test for detecting recurrent or metastatic
      lesions of breast carcinoma. However, the sensitivity for metastases to bone
      appears to be lower than that to other organs. Specificity may be improved by
      more strict attention to patient preparation and better recognition of
      physiologic skeletal muscle or artifactual uptakes.

PMID- 9529288
TI  - Radiotoxicity after iodine-131 therapy for thyroid cancer using the micronucleus
      assay.
AB  - The purpose of the present study was to evaluate the degree of cytological
      radiation damage to lymphocytes after 131I therapy using the cytokinesis-blocked
      micronucleus assay. The chromosomal damage to lymphocytes induced by 131I in vivo
      should result in augmentation of the cells with micronuclei. METHODS: We studied
      25 patients with differentiated thyroid carcinoma who were treated with 3.7 GBq
      of 131I. Isolated lymphocytes collected from patients 1 wk after therapy were
      harvested and treated according to the cytokinesis-blocked method of Fenech and
      Morley. The micronucleus number of micronuclei per 500 binucleated cells were
      scored by visual inspection. As controls, lymphocytes from the same patients
      before therapy were also studied. In an in vitro study, lymphocytes from three
      patients at least 3 mo after therapy were exposed to doses varying from 0.25 to 1
      Gy and studied with the same method. RESULTS: The mean number (mean +/- s.d.) of
      micronuclei after treatment was significantly increased (p < 0.05) as compared to
      control subjects (15.7 +/- 2.7 vs. 5.4 +/- 1.4). Since there was an interval
      ranging from 6 to 20 mo (mean 11.8 mo) between the present and the last
      radioiodine therapy, no significant effect on the frequency of micronucleus with
      cumulative radiation exposure of 131I to lymphocytes was detected. Internal
      radiation absorbed doses estimated for 25 patients were 0.33 +/- 0.09 Gy in this
      external irradiation study. CONCLUSION: The relatively low frequency of
      lymphocyte micronuclei induced by 131I in vivo and lack of significant effect on
      the frequency of lymphocyte micronuclei with cumulative 131I supported the
      contention that short-term nonstochastic damage of this therapy with 3.7 GBq of
      131I in thyroid cancer patients is minimal and reversible.

PMID- 9529289
TI  - Glucose metabolism in human malignant gliomas measured quantitatively with PET, 1
      [C-11]glucose and FDG: analysis of the FDG lumped constant.
AB  - Calculation of the glucose metabolic rate (MRGlc) in brain with PET and 2
      [18F]fluoro-2-deoxy-D-glucose (FDG) requires knowing the rate of uptake of FDG
      relative to glucose from plasma into metabolite pools in the tissue. The
      proportionality factor for this is the FDG lumped constant (LC[FDG]), the ratio
      of the volumes of distribution of FDG and glucose multiplied by the hexokinase
      phosphorylation ratio for the two hexoses, Km(Glc) x Vm(FDG)/Km(FDG) x Vm(Glc) x
      MRGlc equals the FDG metabolic rate (MRFDG) divided by the LC(FDG), i.e., MRGlc =
      MRFDG/LC(FDG) and LC(FDG) = MRFDG/MRGlc. This investigation tested the hypothesis
      that LC(FDG) is significantly higher in gliomas than it is in brain uninvolved
      with tumor. METHODS: We imaged 40 patients with malignant gliomas with 1
      [11C]glucose followed by FDG. The metabolic rates MRGlc and MRFDG were estimated
      for glioma and contralateral brain regions of interest by an optimization program
      based on three-compartment, four-rate constant models for the two hexoses.
      RESULTS: The LC(FDG), estimated as MRFDG/MRGlc, in gliomas was 1.40 +/- 0.46
      (mean +/- s.d.; range = 0.72-3.10), whereas in non-tumor-bearing contralateral
      brain, it was 0.86 +/- 0.14 (range = 0.61-1.21) (p < 0.001, glioma versus
      contralateral brain). CONCLUSION: These data strongly suggest that the glioma
      LC(FDG) exceeds that of contralateral brain, that quantitation of the glioma
      MRGlc with FDG requires knowing the LC(FDG) specific for the glioma and that the
      LC(FDG) of normal brain is higher than previously reported estimates of about
      0.50. 2-Fluoro-2-deoxy-D-glucose/PET studies in which glioma glucose metabolism
      is calculated by the autoradiographic approach with normal brain rate constants
      and LC(FDG) will overestimate glioma MRGlc, to the extent that the glioma LC(FDG)
      exceeds the normal brain LC(FDG). "Hot spots" visualized in FDG/PET studies of
      gliomas represent regions where MRGlc, LC(FDG) or their product is higher in
      glioma than it is in uninvolved brain tissue.

PMID- 9529290
TI  - Immunohistologic assessment of technetium-99m-MIBI uptake in benign and malignant
      breast lesions.
AB  - This study was undertaken to assess the relationship between the degree of 99mTc
      MIBI uptake in breast lesions and the following histologic factors:
      neovascularity, desmoplastic reaction, cellular proliferation and mitochondrial
      density. METHODS: Forty-two patients who previously underwent MIBI breast imaging
      (4 false-negative, 12 false-positive, 15 true-negative, 11 true-positive) were
      studied. Immunohistochemical staining was performed for neovascularity (Factor
      VIII antigen), desmoplasia (alpha-actin antigen), mitochondrial density
      (mitochondrial antigen) and cellular proliferation (MIB-1 antigen). The degree of
      microscopic staining was correlated with region of interest measurements of MIBI
      uptake on scintigraphy. RESULTS: There was a poor correlation between MIBI uptake
      and the degrees of neovascularity (r = 0.08, p > 0.05) and intracellular
      mitochondrial density (r = 0.04, p > 0.05) while there was a moderate correlation
      with cellular proliferation (r = 0.4, p < 0.05) and desmoplasia (r = 0.55, p <
      0.001). CONCLUSION: The degree of MIBI uptake in breast lesions is
      multifactorial, but it appears to be related more to the degree of desmoplastic
      activity and cellular proliferation than neovascularity and mitochondrial
      density.

PMID- 9529291
TI  - Fluorine-18-fluorodeoxyglucose PET versus thallium-201 scintigraphy evaluation of
      thyroid tumors.
AB  - To determine whether PET could help differentiate malignant from benign thyroid
      tumors, 18F-fluorodeoxyglucose (FDG) accumulation and 201Tl scintigraphy were
      examined relative to histological diagnosis. METHODS: Nodular thyroid lesions in
      11 patients were evaluated before surgical resection. Static PET scanning with
      370 MBq FDG was done for 20 min (from 40 to 60 min postinjection) in all
      patients, and standardized uptake values (SUVs) in these lesions were calculated.
      In addition, eight patients were evaluated with dynamic PET scan up to 60 min
      postinjection, and the lesions were further evaluated using graphical analysis.
      Thallium-201 delayed images were visually evaluated in 10 patients. RESULTS: Four
      of 11 nodules were well-differentiated papillary carcinoma, another five were
      benign follicular adenomas, one was a multinodular goiter and another a case of
      chronic thyroiditis that was proved not to contain a nodule. Time-activity curves
      of FDG uptake showed different patterns in malignant and benign tumors. In the
      malignant tumors, FDG uptake increased with time after the tracer injection. By
      contrast, FDG uptake in benign tumors gradually decreased. With use of a cutoff
      value of 5.0 mg/ml for SUV and 10 microl x min(-1) x ml(-1) for Kc (K complex
      value determined using the linear fitting of the time-activity curve of FDG
      accumulation), all of the four malignant nodules and the six benign nodules were
      separated correctly. Chronic thyroiditis had high SUV in the malignant range. Of
      the four patients with thyroid carcinoma, the delayed 201Tl images revealed a
      slightly higher or equal uptake to background activity. In a patient with chronic
      thyroiditis, the delayed 201Tl images revealed diffuse accumulation higher than
      background activity. CONCLUSION: FDG-PET is superior to 201Tl in differentiating
      malignant from benign tumors. Both SUVs and Kc values were useful indexes for
      this discrimination. Although careful evaluation is needed for chronic
      inflammatory lesions, this technique appears to be useful in evaluating thyroid
      nodules.

PMID- 9529292
TI  - Metastatic axillary lymph node technetium-99m-MIBI imaging in primary breast
      cancer.
AB  - Technetium-99m-MIBI scintimammography has been shown to be useful in the
      detection of primary breast cancer. The purpose of this study was to evaluate the
      potential role of scintimammography in detecting axillary lymph node involvement
      in patients undergoing scintimammography to detect primary breast cancer.
      METHODS: A group of 100 women with breast cancer who were scheduled for a Level I
      II axillary dissection were prospectively studied. Scintimammography was
      performed in all patients before histopathologic confirmation of breast cancer.
      Two lateral (prone imaging) views and one anterior (supine) planar thoracic view
      were obtained 10-15 min after the injection of 25-30 mCi 99mTc-MIBI (10 min/view)
      by using a special breast positioning device (foam cushion) placed over the
      imaging table. Both of the axilla were included in the field-of-view. Two
      experienced blinded observers reviewed all cases both from films and from the
      computer screen with contrast adjustment when needed. The site of intravenous
      injection of 99mTc-MIBI was known to the interpreters in order to avoid reading
      any false-positive uptake in the axilla ipsilateral to the injection site.
      RESULTS: A total of 52 patients had no axillary lymph node involvement (611
      negative nodes) while 48 patients had at least one axillary lymph node with
      metastatic involvement (180/502 positive nodes). The sensitivity of
      scintimammography in detecting metastatic axillary lymph node involvement was
      79.2% (38/48), and the specificity was 84.6% (44/52). The positive and the
      negative predictive values were 82.6% (38/46) and 81.5% (44/54), respectively.
      CONCLUSION: This study shows that scintimammography has good diagnostic accuracy
      for detecting axillary lymph node involvement in patients with breast cancer.
      This information should be added to the result of standard scintimammography,
      which requires very minor modifications in order to simultaneously evaluate both
      of the axilla.

PMID- 9529293
TI  - Intravenous and intra-arterial oxygen-15-labeled water and fluorine-18-labeled
      fluorouracil in patients with liver metastases from colorectal carcinoma.
AB  - Intra-arterial chemotherapy can potentially increase drug delivery at the tumor
      sites and has therefore been used for the therapy of metastatic colorectal
      cancer. METHODS: Dynamic PET and [18F]fluorouracil (18F-FU) were used in patients
      with liver metastases from colorectal cancer to examine the pharmacokinetics of
      the drug up to 120 min after intravenous and intra-arterial injection of the same
      dose of fluorouracil (FU). All patients included in the study (n = 15) had
      surgically implanted catheters in the gastroduodenal artery. Dynamic PET studies
      (up to 5 min) with 15O-labeled water were performed for the evaluation of the
      access to the lesions immediately before the 18F-FU study using both
      administration routes. The final evaluation included 24 metastases, obtained from
      15 patients. RESULTS: Of 24 lesions, 21 (87.5%) showed an improved access using
      the intra-arterial approach, and 20 (83.3%) demonstrated a better FU influx after
      intra-arterial 18F-FU infusion. Metastases reached the highest 18F-FU
      concentrations after intra-arterial administration, with a maximum standardized
      uptake values of 18.75 for the FU influx and of 5.03 for FU trapping. Of 24
      metastases, eight (33.3%) demonstrated enhanced FU trapping after the intra
      arterial administration. Cluster analysis revealed a group of metastases (n = 6)
      with a nonperfusion-dependent FU transport using the intravenous application. Of
      these six lesions, five (83.3%) did not show any enhancement of the 18F-FU
      trapping after intra-arterial application. The data gave evidence for at least
      one different, energy-dependent transport system, which can be saturated even
      after intravenous administration of the drug. CONCLUSION: The data show that the
      main limiting factor for a therapy response is the very high and rapid
      elimination of the cytostatic agent out of the tumor cells. Furthermore, it was
      not possible to predict the pharmacokinetics of FU after intra-arterial
      application using an intravenous PET study. It may be possible, using intravenous
      PET double-tracer studies, to identify metastases having a nonperfusion-dependent
      transport system and exclude them from an intra-arterial treatment protocol.

PMID- 9529294
TI  - Bone marrow uptake of thallium-201 before and after therapy in multiple myeloma.
AB  - We describe a patient with multiple myeloma who was found to have diffuse bone
      marrow uptake of 201Tl. Magnetic resonance (MR) imaging of the lumbar spine
      demonstrated abnormal low signal intensity on T1-weighted images and abnormal
      high signal intensity on T2-weighted images. The bone marrow consisted of 68%
      plasma cells, and the serum immunoglobulin (Ig)G concentration was 7900 mg/dL.
      After receiving chemotherapy, the percentage of plasma cells and serum IgG
      concentration declined and there was a decrease in the bone marrow uptake of
      201Tl. However, the MR abnormalities in the lumbar spine showed no change after
      chemotherapy. This patient illustrates a limitation of the use of MR imaging for
      evaluation of disease state in patients with multiple myeloma, and demonstrates
      the potential usefulness of 201Tl imaging in these patients.

PMID- 9529295
TI  - Indium-111- and yttrium-90-labeled human monoclonal immunoglobulin M targeting of
      human ovarian cancer in mice.
AB  - Most patients with ovarian cancer have disease in the peritoneal cavity.
      Treatment of this region is inadequate because recurrences are frequent.
      Increased radiation doses to tumor and, hence, greater tumor control may be
      possible with intraperitoneal (i.p.) administration of radiolabeled human
      monoclonal immunoglobulin M (IgM), which is reactive with tumor-associated
      antigens. METHODS: Biodistribution studies were performed in nude mice bearing
      i.p. nodules of human ovarian cancer after administration of human monoclonal
      IgMlambda (AC6C3-2B12), labeled with 111In or 90Y. Irrelevant 111In-labeled human
      IgMlambda (CH-1B9) and 90Y-aggregate served as specificity controls. RESULTS:
      Intravenous administration of 111In-labeled AC6C3-2B12 produced low tumor and
      high liver and spleen uptake. Intraperitoneal administration of AC6C3-2B12
      labeled with 111In or 90Y resulted in rapid, high tumor uptake (>45% of injected
      dose per gram of tumor at 3 hr) that was at least three-fold higher than any
      normal organ. Biodistribution results were similar for 111In- and 90Y-labeled
      IgM. Tumor uptake of 111In-labeled AC6C3-2B12 was two-fold greater than that of
      111In-labeled CH-1B9. Normal organ uptakes were similar for tumor-reactive and
      irrelevant IgM. Radioimmunoconjugates were retained in the peritoneal cavity for
      a prolonged period of time. Yttrium-90 aggregate demonstrated high tumor and bone
      uptake. CONCLUSION: Higher tumor uptake was observed after i.p. administration of
      tumor-reactive IgM than after irrelevant IgM. The in vivo behavior of tumor
      reactive IgM was similar when it was radiolabeled with either 111In or 90Y.
      Therefore, 111In-based imaging studies can be used to predict the biodistribution
      of subsequently administered 90Y-labeled IgM. Further development of radiolabeled
      AC6C3-2B12 as a diagnostic and therapeutic agent for patients with advanced
      ovarian carcinoma is warranted.

PMID- 9529296
TI  - Pharmacokinetic model of iodine-131-G250 antibody in renal cell carcinoma
      patients.
AB  - A model that describes the pharmacokinetic distribution of 131I-labeled G250
      antibody is developed. METHODS: Previously collected pharmacokinetic data from a
      Phase I-II study of 131I-G250 murine antibody against renal cell carcinoma were
      used to develop a mathematical model describing antibody clearance from serum and
      the whole body. Survey meter measurements, obtained while the patient was under
      radiation precautions, and imaging data, obtained at later times, were combined
      to evaluate whole-body clearance kinetics over an extended period. RESULTS: A
      linear two-compartment model was found to provide good fits to the data. The
      antibody was injected into Compartment 1, the initial distribution volume (Vd) of
      the antibody, which included serum. The antibody exchanged with the rest of the
      body, Compartment 2, and was eventually excreted. Data from 13 of the 16 patients
      fit the model with unique parameters; the maximum, median and minimum values for
      model-derived Vd were 6.3, 3.7 and 2.11, respectively. The maximum, median and
      minimum values for the excretion rate were 8 x 10(-2), 2.4 x 10(-2) and 1.3 x 10(
      2) hr(-1), respectively. Parameter sensitivity analysis showed that a change in
      the transfer rate constant from serum to the rest of the body had the greatest
      effect on serum cumulative activity and that the rate constant for excretion had
      the greatest effect on whole-body cumulative activity. CONCLUSION: A linear two
      compartment model was adequate in describing the serum and whole-body kinetics of
      G250 antibody distribution. The median initial distribution volume predicted by
      the model was consistent with the nominal value of 3.81. A wide variability in
      fitted parameters was observed among patients, reflecting the differences in
      individual patient clearance and exchange kinetics of G250 antibody. By selecting
      median parameter values, such a model may be used to evaluate and design
      prolonged multiple administration radioimmunotherapy protocols.

PMID- 9529297
TI  - Issues surrounding preparation, information and handling the child and parent in
      nuclear medicine.
AB  - A successful pediatric nuclear medicine examination can be defined as a high
      quality study coupled with the child and parent feeling that their emotional
      needs have been considered. To achieve this goal requires a team approach by all
      members of the nuclear medicine department as well as a comprehensive explanation
      of the procedure to the child and parent. Success often depends not so much on a
      department with the latest gamma camera but a department with an understanding of
      the needs of children and value of small items such as toys, posters, appropriate
      books and so on. The recognition that a child requires twice as long as an adult
      for the same examination dictates an appropriate appointment system to ensure
      that the staff have sufficient time to devote to the child and parent.

PMID- 9529298
TI  - Cobalt-57 and technetium-99m-HMPAO-labeled leukocytes for visualization of
      ischemic infarcts.
AB  - Previous studies have shown the usefulness of divalent cobalt isotopes to
      visualize cerebral damage after stroke. The site of accumulation of cobalt ion is
      unknown but may be explained by neuronal influx, analogous to that of calcium
      ion. Additionally, uptake may be due to infiltrating leukocytes or protein-bound
      cobalt. The aims of this study were to compare 57Co-SPECT with leukocyte SPECT
      and to compare the SPECT findings with clinical outcome as scored by the Orgogozo
      scale. MATERIALS: Ten patients with a CT scan positive for middle cerebral artery
      infarcts were included in the study (7 men, 3 women; mean age 70 yr). Technetium
      99m leukocyte and cobalt-SPECT (interval 2-4 days) were made with a double-headed
      gamma camera, after the injection of 10-15 mCi 99mTc-HMPAO-labeled leukocytes and
      0.4 mCi 57Co, respectively. Scans were performed within 5-30 days after onset of
      the first symptoms. Regions of interest (ROI) containing the area of infarction
      in the slices displaying enhanced radioactivity or the middle cerebral artery
      (MCA) region in four successive slices were defined for calculating enhancement
      ratios. The 99mTc leukocyte enhancement ratio (LER) and cobalt enhancement ratio
      (CER) were defined as the quotient of radioactivity in the ROI and an identical
      contralateral ROI. The MCA stroke-scale according to Orgogozo was used to assess
      neurological deficits at the time of scanning and discharge. RESULTS: Cobalt-57
      and 99mTc-HMPAO showed uptake in the infarcted brain area in five patients; the
      quantitative uptake in the infarcted brain area of the two tracers correlated
      significantly (p < 0.05). Both the LER and the CER correlated significantly (p <
      0.05) with the Orgogozo score at the time of scanning. Only the LER correlated
      significantly (p < 0.05) with the Orgogozo score at discharge. CONCLUSION: Uptake
      of cobalt and leukocytes in the peri-infarct tissue suggests that 57Co may
      visualize a component of the inflammatory response. Divalent 57Co may be
      convenient to predict clinical prognosis after stroke.

PMID- 9529299
TI  - Evaluation of carbon-11-labeled KF17837: a potential CNS adenosine A2a receptor
      ligand.
AB  - The 11C-labeled KF17837 ([7-methyl-11C](E)-8-(3,4-dimethoxystyryl)-1,3-dipropyl-7
      methylxa nthine) was evaluated as a PET ligand for mapping adenosine A2a
      receptors in the central nervous system (CNS). METHODS: The regional brain
      distribution of [11C]KF17837 and the effect of adenosine antagonists on the
      distribution were measured in mice by the tissue sampling method. In rats, the
      regional brain uptake of [11C]KF17837 and the effect of carrier KF17837 was
      visualized by autoradiography. Imaging of the monkey brain with [11C]KF17837 was
      performed by PET. RESULTS: In mice, a high uptake of [11C]KF17837 was found in
      the striatum in which A2a receptors were highly enriched. The uptake was
      decreased by co-injection of carrier KF17837 or a xanthine-type A2a antagonist
      CSC but not by nonxanthine-type A2a antagonists ZM 241385 or SCH 58261, or an A1
      antagonist KF15372. In the rat brain, [11C]KF17837 was accumulated higher in the
      striatum than in other brain regions, and the uptake was blocked by co-injection
      of carrier KF17837. In a monkey PET study, a high striatal uptake of
      radioactivity was observed. CONCLUSION: Carbon-11-KF17837 binds to adenosine A2a
      receptors in the striatum. However, the presence of an unknown but specific
      binding site for xanthine-type compounds also was suggested in the other brain
      regions. The results also suggested that the in vivo receptor-binding sites of
      xanthine-type ligands are slightly different from those of nonxanthine-type A2a
      antagonists.

PMID- 9529300
TI  - Fully automated establishment of stereotaxic image orientation in six degrees of
      freedom for technetium-99m-ECD brain SPECT.
AB  - Anatomical localization requires establishing an anatomical space within the
      image matrix. We developed a fast, fully automated method to establish the image
      orientation for 99mTc-ethylcysteinate dimer (ECD) brain SPECT images. METHODS:
      The image orientation of ECD brain SPECT images was established in four stages.
      First, the brain surface was edge-detected as an isosurface at an adaptive
      threshold. Second, a "convex hull" was determined for the isosurface to minimize
      regional variability in brain shape. A principal axis transformation and a
      symmetry vector analysis were applied to the convex hull to resolve the
      craniocaudal direction and to estimate the midsagittal plane. Third, the brain
      orientation was refined from this estimate by location of the interhemispheric
      fissure, the tentorial groove and the frontotemporal groove on the isosurface.
      Last, the intercommissural (anterior commissure-posterior commissure, or AC-PC)
      line was detected on the midsagittal slice, and the Talairach grid was scaled to
      fit the maximal brain dimensions from the AC-PC line. RESULTS: The average
      absolute errors were 2.3 degrees +/- 1.5 degrees and 1.08 mm +/- 1.11 mm for the
      midsagittal plane (n = 24) and 2.04 degrees +/- 0.80 degrees, 2.0% +/- 1.8% of
      the brain length and 2.3% +/- 2.2% of the brain height for the AC-PC line (n =
      8). In addition, this program successfully established the image orientation in
      94 of 100 clinical ECD brain SPECT studies. Processing time was <40 sec for 128 x
      128 x 50 matrices on a DEC Alpha workstation. CONCLUSION: We have developed a
      fast, robust and fully automated method that determines the orientation of ECD
      brain SPECT images. This objective method of standardizing the image orientation
      should be useful for anatomical localization and clinical interpretation of these
      images.

PMID- 9529301
TI  - Performance evaluation of the Pico-Count flow-through detector for use in
      cerebral blood flow PET studies.
AB  - This study evaluated the Pico-Count (Bioscan, Inc., Washington, DC) flow-through
      radioactivity detector, designed for use in PET studies of cerebral blood flow.
      METHODS: The Pico-Count detects the two 511-keV positron annihilation photons
      with two bismuth germanate detectors operating in coincidence. The detectors,
      photomultipliers and preamps are housed within a 12 cm x 9 cm x 22 cm box, which
      includes 16 mm of lead shielding, to allow placement of the detector within 15 cm
      of the sampling site. The counting electronics are housed in a remote box, which
      is connected to a laptop computer for process control. The dwell time per sample
      and the number of samples to collect are entered through the computer and can
      vary throughout the study. Approximately 22 cm of arterial tubing (which contains
      0.11 ml of blood) is looped between the detectors. Typically, blood is withdrawn
      with a syringe pump at a rate of 2.75 ml/min, which corresponds to a flow rate in
      the tubing of 9.2 cm/sec. Dispersion within the arterial catheter is measured by
      observing the response to an input step function and is well-modeled as a
      monoexponential. RESULTS: The sensitivity is 270 Hz/(microCi/ml), which
      corresponds to detecting 6.9% of the positron decays occurring within the
      detector. The peak counting rate after a 12-mCi injection is approximately 2100
      Hz, with the background being less than 0.2%. The dispersion time constant is 1.3
      sec, and the delay between radioactivity present at the catheter tip and that
      measured by the detector is 4.1 sec. The cutoff in the power spectral density of
      typical human arterial blood time radioactivity curves is far less than the
      corresponding cutoff for the dispersion function. CONCLUSION: The Pico-Count is
      an excellent detector for continuously monitoring positron radioactivity in
      blood. Depending on the application, dispersion correction for the detection
      apparatus may not be needed.

PMID- 9529302
TI  - Comparison of technetium-99m-MDP, technetium-99m-WBC and technetium-99m-HIG in
      musculoskeletal inflammation.
AB  - This study compared three radionuclide techniques in distinguishing
      musculoskeletal infection from noninfectious inflammation. METHODS: Thirty-five
      orthopedic patients with suspected musculoskeletal infection were examined using
      three radionuclide techniques in sequence: triphasic bone scintigraphy, 99mTc
      radioleukocytes (99mTc-WBC) scintigraphy and 99mTc human immunoglobulin (99mTc
      Hig) scintigraphy. Two "early" and "late" acquisitions were performed, at 4-6 hr
      and 20-24 hr postinjection, respectively. Patients who were diagnosed as
      suffering from noninflammatory lesions became the controls. We calcu"late"d for
      all studies one index of inflammation (Infl) as the ratio between counts in the
      uptake area and counts in an equal area of normal tissue. RESULTS: The "early"
      radiolabeled leukocytes and "late" Hig scintigraphy allowed the greatest ability
      to distinguish between infections and noninfectious inflammations (p < 0.011 and
      p < 0.016) with a sensitivity of 96.6% and 96.5% and specificity of 71% and 100%,
      respectively. Hig and radioleukocytes allowed distinguishing infections from
      noninflammatory diseases at both examinations. CONCLUSION: The "early"
      radioleukocyte scintigraphy allowed us to separate infections from noninfectious
      inflammations. In contrast, the same result can be obtained only with the "late"
      scan in the Hig study, but Hig mapped the spread of the inflammation into soft
      tissues better. Hig might be an alternative to radioleukocytes because of its
      simple preparation, similar accuracy and safety.

PMID- 9529303
TI  - Prospective study of simultaneous orthoiodohippurate and
      diethylenetriaminepentaacetic acid captopril renography. The Einstein/Cornell
      Collaborative Hypertension Group.
AB  - Captopril renography (CR) has been established in the past 10 yr as a useful
      diagnostic test for renovascular hypertension. However, direct comparison of
      tubular and glomerular tracers, quantitative criteria, comparison of quantitative
      and qualitative results and the reliability of the results in renal failure have
      not been described in a systematic, prospective fashion. METHODS: Same-day
      baseline and CR using 99mTc-labeled diethylenetriaminepentaacetic acid (DTPA) and
      [131I]orthoiodohippurate (OIH) were simultaneously performed in two groups of
      hypertensive subjects, one with demographically defined essential hypertension (n
      = 43) and the other (n = 60) with a high prevalence of renovascular disease,
      defined with angiograms. Quantitative criteria for abnormal CR were derived from
      results among the subjects with essential hypertension. Qualitative analysis was
      performed using widely established criteria. RESULTS: There were no statistically
      significant differences between quantitative and qualitative accuracy, between
      OIH and DTPA or among quantitative parameters. The best accuracies for
      quantitative CR were 56% with DTPA (n = 57) and 60% with OIH (n = 60), in both
      cases using the relative renal uptake parameter. Qualitative CR (n = 60) had
      accuracies of 43% (DTPA) and 50% (OIH), both hindered by 29 (DTPA) and 25 (OIH)
      abnormal but nondiagnostic studies. Two false-positive studies were detected.
      Twenty-seven of 29 nondiagnostic studies were associated with a glomerular
      filtration rate of <50 ml/min (n = 17), one small kidney (n = 17) and/or
      bilateral renal artery stenosis (n = 16). Supplemental measurement of in vitro
      stimulated plasma renin activity insignificantly (p > 0.10) and improved
      accuracies to 63% (DTPA) and 70% (OIH), without introducing additional false
      positive tests. CONCLUSION: Orthoiodohippurate and DTPA have comparable accuracy
      in prospective simultaneous evaluation of CR. False-positive studies are fewer
      than 5%. The accuracies of quantitative and qualitative criteria do not differ
      significantly but may be improved by supplemental use of the in vitro stimulated
      plasma renin activity. In individuals with renal insufficiency, small kidneys
      and/or bilateral renal artery disease, up to 48% of CR studies are abnormal but
      nondiagnostic.

PMID- 9529304
TI  - Technetium-99m-DTPA-galactosyl human serum albumin liver scintigraphy evaluation
      of regional CT/MRI attenuation/signal intensity differences.
AB  - Regional attenuation/signal intensity differences seen on CT/magnetic resonance
      imaging can be a clue in detecting regional hepatic blood flow abnormality.
      Sometimes, however, they can be misinterpreted as a hepatic neoplasm or, in the
      case of a true neoplasm, they can lead to an overestimation of its size because
      these regions often have similar attenuation or signal intensity to hepatic
      neoplasms. We evaluated 99mTc-diethylenetriaminepentaacetic acid-galactosyl human
      serum albumin (99mTc-DTPA-GSA) liver scintigrams in patients manifesting regional
      attenuation/signal intensity differences to further analyze the findings.
      METHODS: Technetium-99m-DTPA-GSA scintigrams of 23 patients with regional
      attenuation/signal intensity differences in the liver at dynamic contrast
      enhanced CT/magnetic resonance imaging were evaluated. The causes of the
      differences were arterioportal (AP) shunts in seven patients, decreases in the
      portal venous flow in seven patients, occlusion of right hepatic vein in one
      patient, confluent hepatic fibrosis in one patient and unknown in seven patients.
      The accumulation of 99mTc-DTPA-GSA was compared with each known cause of
      attenuation/signal intensity difference. Count ratios of the regions to normal
      hepatic parenchyma also were calculated in all cases. RESULTS: In AP shunts, none
      of seven patients showed any decreased accumulation in the region. Accumulation
      of 99mTc-DTPA-GSA decreased in six of seven patients who had decreases in portal
      venous flow; this incidence was significantly higher than that in patients who
      had AP shunts (p < 0.005). In cases of unknown cause, two of seven patients
      showed a decrease in accumulation, but the other five showed no such decrease.
      The one patient with occlusion of the right hepatic vein showed no decrease, but
      the confluent hepatic fibrosis showed a significant decrease. The count ratio in
      AP shunts was significantly larger than that of the decrease in the portal venous
      flow (p < 0.005). CONCLUSION: Technetium-99m-DTPA-GSA accumulation in AP shunts
      has a different pattern from that found in patients with a decrease in portal
      venous flow. Therefore, differentiation between AP shunts, which showed no
      decrease in 99mTc-DTPA-GSA accumulation, and hepatic neoplasms can be made more
      easily.

PMID- 9529305
TI  - Indium-111-pentetreotide in Graves' disease.
AB  - Thyroidal and orbital lymphocytic infiltration in Graves' disease, as well as
      identification of somatostatin receptors on lymphocytes, has provided a rationale
      for receptor imaging with the radiolabeled somatostatin analog pentetreotide.
      Recently, we demonstrated that in contrast to controls, Graves' patients showed
      markedly increased orbital accumulation of pentetreotide. Longitudinal and follow
      up data are presented here. METHODS: In 20 (16 hyperthyroid) Graves' patients
      with active eye disease, planar (thyroid) and SPECT (orbit) images were performed
      4 and 24 hr after injection of 111In-pentetreotide (222 MBq) before and 3 mo
      after starting antithyroid and combined steroid and orbital radiotherapy.
      RESULTS: Thyroidal uptake decreased during methimazole treatment (4 hr
      postinjection, median: hyperthyroid 989 counts/pixel/MBq injected activity,
      euthyroid 253 counts, p = 0.001; 24 hr, 437 versus 95 counts/pixel/MBq, p =
      0.005). Fourteen patients (70%) responded to steroid and radiotherapy. The
      pentetreotide orbit-to-brain ratio decreased markedly after completion of therapy
      (4 hr: 25 before versus 6.2 after therapy, p = 0.0003; 24 hr: 9.6 versus 2.7, p =
      0.003). A high pretreatment ratio correlated with a response to therapy (p =
      0.001: in 14 of 16 patients with a ratio > 10, 4 hr postinjection, ophthalmopathy
      improved; positive predictive value: 90%; median activity score before 6 versus 2
      after therapy, p = 0.0001) in contrast to none of the four cases with a ratio
      less than 10 (score 5 versus 4, p = 0.08). CONCLUSION: Pentetreotide scans may be
      regarded as a semiobjective tool in the evaluation of Graves' disease, both at
      initial stages as well as during treatment.

PMID- 9529306
TI  - Pleomorphic adenoma of the salivary glands: correlation between gallium-67 uptake
      and histopathological components.
AB  - We correlated 67Ga uptake and histopathological findings in pleomorphic adenomas
      of the salivary glands. METHODS: Sixty-two pleomorphic adenomas of the salivary
      glands were visually graded by degree of 67Ga uptake as negative, weakly positive
      or strongly positive in comparison to uptake in the nasal cavity. These adenomas
      were re-examined pathologically and classified as epithelial, intermediate or
      mesenchymal type according to their dominant histological components. The
      pathological presence of marginal invasion or associated sialoadenitis was also
      re-examined. RESULTS: Eighteen adenomas were classified as strongly positive,
      eight as weakly positive and 36 as negative. Nine (50%) of the 18 strongly
      positive adenomas were of the epithelial type and the other nine (50%) strongly
      positive adenomas were of the intermediate type. While none of the strongly
      positive adenomas were of the mesenchymal type, 27 (75%) of the 36 negative
      adenomas were of the mesenchymal type. Six (75%) of the eight weakly positive
      adenomas were of the intermediate type. About half of the adenomas showed
      marginal invasion regardless of the grade of 67Ga uptake. None of the strongly
      positive adenomas were associated with sialoadenitis. CONCLUSION: The epithelial
      component of pleomorphic adenomas may be responsible for 67Ga uptake. The
      presence of marginal invasion or associated sialoadenitis has little relation to
      67Ga uptake in pleomorphic adenomas.

PMID- 9529307
TI  - Pentavalent technetium-99m-dimercaptosuccinic acid scintigraphy in renal
      osteodystrophy.
AB  - Pentavalent 99mTc-dimercaptosuccinic acid (DMSA) scintigraphy and 99mTc
      hydroxymethylene diphosphonate (HMDP) bone scan were performed in one patient
      with renal osteodystrophy (ROD) before and after vitamin D3 pulse therapy. The
      bone scan showed diffusely increased tracer uptake in the whole skeleton, and no
      change of tracer distribution was noted before or after vitamin D3 pulse therapy.
      However, 99mTc(V)-DMSA scintigraphy revealed diffusely increased tracer uptake in
      the whole skeleton before therapy, and markedly decreased tracer uptake in the
      bones was seen at 5 mo after therapy. Increased uptake of 99mTc(V)-DMSA was
      observed at 7 mo after therapy, which reflected the laboratory findings.
      Technetium-99m-(V)-DMSA scintigraphy appeared to be more sensitive than the
      conventional 99mTc-HMDP bone scan in assessing the characteristics and
      therapeutic effect of bone disease in ROD.

PMID- 9529308
TI  - Effect of inhaled surfactant on pulmonary deposition and clearance of technetium
      99m-DTPA radioaerosol.
AB  - To establish the effect of an aerosolized synthetic surfactant (Exosurf) on
      pulmonary 99mTc-diethylenetriamine pentaacetic acid (DTPA) aerosol deposition and
      clearance, radioaerosol studies were performed at varying times and under varying
      conditions after surfactant inhalation in canine lungs. METHODS: Twenty-three
      dogs had a baseline 99mTc-DTPA study; 2 days later the study was repeated after
      inhalation of a 1.5-ml/kg dose of Exosurf aerosolized by an ultrasonic nebulizer.
      The clearance half-time (T1/2) of 99mTc-DTPA from each lung was measured at
      different times (from 10 min to 3 hr) after Exosurf inhalation. For comparison,
      five animals had a 99mTc-DTPA study 10 min after inhalation of the same dose of
      saline as Exosurf. An additional five animals inhaled a 99mTc-DTPA-Exosurf
      mixture to investigate the distribution of Exosurf. RESULTS: Technetium-99m-DTPA
      distributed uniformly without significant changes in penetration indexes before
      and after inhalation of Exosurf and the 99mTc-DTPA-Exosurf mixture. After Exosurf
      inhalation, 99mTc-DTPA clearance at 10 min (T1/2; 35.6 +/- 8.7 min; n = 6) and 40
      min (29.4 +/- 6.3 min; n = 4) was significantly prolonged compared with the
      matched baseline values (24.7 +/- 6.4 min, p < 0.0001; and 21.7 +/- 8.9 min, p =
      0.01, respectively). However, later clearance times were not prolonged. By
      contrast, after saline inhalation, 99mTc-DTPA distributed inhomogeneously, and
      clearance times T1/2) were not altered from the matched baseline values.
      CONCLUSION: Aerosolized Exosurf distributes homogeneously in the lungs. Exosurf
      initially retards 99mTc-DTPA aerosol clearance, but 99mTc-DTPA transalveolar
      clearance returns to baseline rates within 1-2 hr. Technetium-99m-DTPA aerosol
      clearance measurements can be used to monitor the effect of inhaled Exosurf on
      pulmonary epithelial integrity.

PMID- 9529310
TI  - An alternative method to normalize clinical FDG studies.
AB  - An alternative method of determining the integrated input function, necessary in
      the quantitative [18F]fluorodeoxyglucose (FDG) autoradiographic model, has been
      developed. Using erythrocytes as reference tissue, researchers require only one
      blood sample after injection of FDG to obtain the integrated input function.
      METHODS: The amount of FDG-6-PO4 in the erythrocytes is proportional to their
      exposure to FDG, that is, the integrated input function. Free FDG is removed by
      washing the erythrocytes twice. Inter- and intraindividual differences of the
      metabolic rate of erythrocytes are corrected for by an in vitro incubation with a
      known amount of FDG. RESULTS: Validation of the proposed method was done by
      correlating the integrated input function, based on the glucose metabolism of the
      erythrocytes, to the integrated input function obtained by multiple venous blood
      samples. The new method provides the integrated input function with an accuracy
      better than +/-8%. CONCLUSION: By using erythrocytes as a reference tissue,
      researchers can determine the integrated input function in the quantitative FDG
      autoradiographic model with an accuracy sufficient for clinical PET studies. The
      simplicity of the method also makes it suitable for FDG studies on small
      children. With two samples, the method can also be used for a simplified
      graphical Patlak analysis.

PMID- 9529309
TI  - Biological dosimetry of bone marrow for incorporated yttrium-90.
AB  - The biological response of bone marrow to incorporated radionuclides depends on
      several factors such as absorbed dose, dose rate, proliferation and marrow
      reserve. The determination of the dose rate and absorbed dose to bone marrow from
      incorporated radionuclides is complex. This research used survival of granulocyte
      macrophage colony-forming cells (GM-CFCs) as a biological dosimeter to determine
      experimentally the dose rate and dose to bone marrow after administration of 90Y
      citrate. METHODS: The radiochemical 90Y-citrate was administered intravenously to
      Swiss Webster mice. Biokinetics studies indicated that the injected 90Y quickly
      localized in the femurs (0.8% ID/femur) and cleared with an effective half-time
      of 62 hr. Subsequently, GM-CFC survival was determined as a function of femur
      uptake and injected activity. Finally, to calibrate GM-CFC survival as a
      biological dosimeter, mice were irradiated with external 137Cs gamma rays at dose
      rates that decreased exponentially with a half-time of 62 hr. RESULTS: Femur
      uptake was linearly proportional to injected activity. The survival of GM-CFCs
      was exponentially dependent on both the initial 90Y femur activity and the
      initial dose rate from external 137Cs gamma rays with 5.1 kBq/femur and 1.9
      cGy/hr, respectively, required to achieve 37% survival. Thus, 90Y-citrate
      delivers a dose rate of 0.37 cGy/hr to the femoral marrow per kBq of femur
      activity and the dose rate decreased with an effective half-time of 62 hr.
      CONCLUSION: Survival of GM-CFCs can serve as a biological dosimeter to
      experimentally determine the dose rate kinetics in bone marrow.

PMID- 9529311
TI  - Photon energy recovery: a method to improve the effective energy resolution of
      gamma cameras.
AB  - One of the major limitations of gamma cameras is their relatively poor energy
      resolution. The main practical consequence of this is that the detection of both
      scattered and unscattered photons in the photopeak energy window, affecting image
      contrast and resolution, makes the data inconsistent with the assumption of
      scatter-free projection data in reconstruction and attenuation correction
      algorithms. Here, we proposed a method to improve the effective energy resolution
      of scintigraphic acquisitions. This method is called photon energy recovery
      (PER). METHODS: Photon energy recovery is based on a spectral deconvolution
      analysis and uses iterative recurrent linear regressions. In practice, PER only
      required splitting the photopeak energy window into several subwindows and did
      not need list mode acquisitions. The method was fully automated. Photon energy
      recovery was quantitatively validated on 99mTc planar images using a Monte Carlo
      simulation and a real phantom and was illustrated by a bone study. RESULTS: The
      Monte Carlo simulation demonstrated that convergence was reached within
      relatively few (10-15) iterations. Photon energy recovery led to a considerable
      quantitative improvement because the mean error between the photopeak energy
      window image and the true unscattered image was equal to 8.72 s.d. (the mean
      error between one image and the true image was the mean of the differences
      between the two images; the difference is expressed as several s.d., where s.d.
      was the square root of the true value), whereas the mean error between the 140
      keV PER image and the true unscattered image was only equal to 2.70. Moreover,
      the true and PER spectra were highly correlated. The real phantom data pointed
      out that the counts in the 140-keV PER image calculated from the images acquired
      "with scatter" were not very different from the true counts given by the "scatter
      free" reference image. Planar pelvic bone scintigraphy demonstrated the
      advantages of PER because contrast increased when only unscattered photons were
      selected. CONCLUSION: Photon energy recovery is a stable and automated method
      that allows recovery of the correct value of the photon energy after a
      scintigraphic acquisition. Its ability to separate scattered from unscattered
      events has been quantitatively validated.

PMID- 9529312
TI  - A comparison of 180 degrees and 360 degrees acquisition for attenuation
      compensated thallium-201 SPECT images.
AB  - This study compared attenuation compensated, myocardial SPECT images
      reconstructed from 180 degrees and 360 degrees data to determine if either data
      acquisition method might yield improved image quality. Specifically, this study
      analyzed how the use of either 180 degrees or 360 degrees data affects: (a) the
      relative count density distribution, (b) defect contrast and (c) level of
      statistical noise in the left ventricular (LV) wall in the reconstructed SPECT
      images. METHODS: Using the three-dimensional MCAT phantom simulating 201Tl uptake
      in the upper torso and the SIMSET Monte Carlo code, noise-free projection
      datasets for both 180 degrees (45 degrees LPO to 45 degrees RAO) and 360 degrees
      acquisition were generated with the effects of nonuniform attenuation, collimator
      detector response and scatter. In addition, low-noise experimental phantom data
      were acquired over 180 degrees and 360 degrees. Assuming the same total
      acquisition time, four sets of noisy projection data were simulated from scaled
      noise-free, simulated data for the following acquisitions: (a) 180 degrees and
      (b) 360 degrees data acquired on a 90 degrees dual-detector system and (c) 180
      degrees and (d) 360 degrees data acquired on a 120 degrees triple-detector
      system. For each of the four acquisition schemes, 400 realizations of noisy
      projection data were generated, and the normalized s.d. in the reconstructed
      images was calculated for five ROIs in the LV wall. Images were reconstructed
      with nonuniform attenuation compensation using ML-EM algorithm for 25, 50 and 75
      iterations. RESULTS: Both the simulated noise-free and experimental low-noise
      images reconstructed from 180 degrees and 360 degrees data showed nearly
      identical count densities and defect contrasts in the LV wall. For the 90 degrees
      dual-detector system, 180 degrees images showed less noise, while for the 120
      degrees triple-detector system, 360 degrees showed less noise; however, these
      differences in noise level were extremely small after a smoothing filter was
      applied. The 180 degrees images acquired with the 90 degrees dual-detector system
      showed the same noise level as the 360 degrees images acquired with the 120
      degrees triple-detector system, so neither system geometry had an advantage with
      respect to reduced noise in the SPECT images. CONCLUSION: When nonuniform
      attenuation compensation is included in the reconstruction, the count density in
      the LV wall is nearly identical for 180 degrees and 360 degrees SPECT images, and
      the 90 degrees dual-detector and 120 degrees triple-detector SPECT systems
      produced similar SPECT images for the same total acquisition time.

PMID- 9529313
TI  - Correct use of dose calibrator values.

PMID- 9529314
TI  - Multiple hemopoietic defects and lymphoid hyperplasia in mice lacking the
      transcriptional activation domain of the c-Rel protein.
AB  - The c-rel protooncogene encodes a member of the Rel/nuclear factor (NF)-kappaB
      family of transcriptional factors. To assess the role of the transcriptional
      activation domain of c-Rel in vivo, we generated mice expressing a truncated c
      Rel (Deltac-Rel) that lacks the COOH-terminal region, but retains a functional
      Rel homology domain. Mice with an homozygous mutation in the c-rel region
      encoding the COOH terminus of c-Rel (c-relDeltaCT/DeltaCT) display marked defects
      in proliferative and immune functions. c-relDeltaCT/DeltaCT animals present
      histopathological alterations of hemopoietic tissues, such as an enlarged spleen
      due to lymphoid hyperplasia, extramedullary hematopoiesis, and bone marrow
      hypoplasia. In older c-relDeltaCT/DeltaCT mice, lymphoid hyperplasia was also
      detected in lymph nodes, liver, lung, and stomach. These animals present a more
      severe phenotype than mice lacking the entire c-Rel protein. Thus, in c
      relDeltaCT/DeltaCT mice, the lack of c-Rel activity is less efficiently
      compensated by other NF-kappaB proteins.

PMID- 9529315
TI  - Chronic inflammation and susceptibility to bacterial infections in mice lacking
      the polypeptide (p)105 precursor (NF-kappaB1) but expressing p50.
AB  - The polypeptide (p)50 molecule, a subunit of nuclear factor (NF)-kappaB, is
      produced after proteolytic processing of the p105 precursor (NF-kappaB1).
      Although the p105 precursor has been postulated to play a role in the regulation
      of the Rel/NF-kappaB activity, its physiological relevance remains unclear. To
      investigate that, we generated mutant mice lacking the COOH terminal half of the
      p105 precursor, but expressing the p50 product (p105-/-). These mutant mice
      displayed an inflammatory phenotype composed of lymphocytic infiltration in lungs
      and liver, and an increased susceptibility to opportunistic infections.
      Enlargement of multiple lymph nodes, splenomegaly due to erythrocytic
      extramedullary hematopoiesis, and lymphoid hyperplasia were also observed in p105
      /- mice. Cytokine production in p105-/- macrophages was severely impaired,
      whereas proliferative responses of p105-/- B cells were increased. T cell
      functions were only moderately impaired in mutant mice. Loss of p105 also led to
      enhanced constitutive p50 homodimer and inducible NF-kappaB activities in
      unstimulated and stimulated cells, respectively. As several genes regulated by
      Rel/NF-kappaB were upregulated in p105-/- thymus but downregulated in p105-/-
      macrophages, the enhanced p50 homodimers appear to function as transcriptional
      activators or repressors, depending on the cell type. Thus, the p105 precursor is
      indispensable in the control of p50 activity, and lack of the precursor has
      distinct effects on different cells.

PMID- 9529316
TI  - The sequential role of lymphotoxin and B cells in the development of splenic
      follicles.
AB  - The transfer of lymphocytes into severe combined immunodeficiency (SCID) mice
      induces a series of histological changes in the spleen, including the appearance
      of mature follicular dendritic cells (FDCs). Studies were undertaken to clarify
      the role of lymphotoxin (LT) in this process. The results show that SCID mice
      have a small and partially differentiated white pulp containing marginal zone and
      interdigitating dendritic cells, but lacking FDCs. Transferred spleen cells can
      segregate into T and B cell areas shortly after their injection to SCID mice.
      This ability is dependent on signaling through LT-beta receptor (LT-betaR), since
      blocking ligand-receptor interaction in recipient SCID mice ablates the capacity
      of the transferred cells to segregate. A week after lymphocyte transfer, host
      derived FDCs appeared in the reconstituted SCID mice. This induction of FDCs is
      dependent on LT-betaR signaling by B cells since LT-alpha-/- B cells are
      incapable of inducing development of FDCs in SCID mice, even after cotransfer of
      LT-alpha+/+ T cells. Therefore, LT plays at least two discrete roles in splenic
      organization. First, it appears that LT induces the differentiation of the white
      pulp to create sites for lymphocyte segregation. Second, LT expression by B cells
      drives the maturation of FDCs and the organization of B cell follicles.

PMID- 9529317
TI  - B lymphocytes induce the formation of follicular dendritic cell clusters in a
      lymphotoxin alpha-dependent fashion.
AB  - Lymphotoxin (LT)alpha is expressed by activated T cells, especially CD4(+) T
      helper type 1 cells, and by activated B and natural killer cells, but the
      functions of this molecule in vivo are incompletely defined. We have previously
      shown that follicular dendritic cell (FDC) clusters and germinal centers (GCs)
      are absent from the peripheral lymphoid tissues of LTalpha-deficient (LTalpha-/-)
      mice. LTalpha-/- mice produce high levels of antigen-specific immunoglobulin
      (Ig)M, but very low levels of IgG after immunization with sheep red blood cells.
      We show here that LTalpha-expressing B cells are essential for the recovery of
      primary, secondary, and memory humoral immune responses in LTalpha-/- mice. It is
      not necessary for T cells to express LTalpha to support these immune functions.
      Importantly, LTalpha-expressing B cells alone are essential and sufficient for
      the formation of FDC clusters. Once these clusters are formed by LTalpha
      expressing B cells, then LTalpha-deficient T cells can interact with B cells to
      generate GCs and productive class-switched antibody responses. Thus, B cells
      themselves provide an essential signal that induces and maintains the lymphoid
      microenvironment essential for GC formation and class-switched Ig responses.

PMID- 9529318
TI  - Neutrophil granulocyte-committed cells can be driven to acquire dendritic cell
      characteristics.
AB  - Polymorphonuclear granulocytes (PMNs) are thought to fulfill their role in host
      defense primarily via phagocytosis and release of cytotoxic compounds and to be
      inefficient in antigen presentation and stimulation of specific T cells.
      Dendritic cells (DCs), in contrast, are potent antigen-presenting cells with the
      unique capacity to initiate primary immune responses. We demonstrate here that
      highly purified lactoferrin-positive immediate precursors of end-stage
      neutrophilic PMN (PMNp) can be reverted in their functional maturation program
      and driven to acquire characteristic DC features. Upon culture with the cytokine
      combination granulocyte/macrophage colony-stimulating factor plus interleukin 4
      plus tumor necrosis factor alpha, they develop DC morphology and acquire
      molecular features characteristic for DCs. These molecular changes include neo
      expression of the DC-associated surface molecules cluster of differentiation
      (CD)1a, CD1b, CD1c, human leukocyte antigen (HLA)-DR, HLA-DQ, CD80, CD86, CD40,
      CD54, and CD5, and downregulation of CD15 and CD65s. Additional stimulation with
      CD40 ligand induces also expression of CD83 and upregulates CD80, CD86, and HLA
      DR. The neutrophil-derived DCs are potent T cell stimulators in allogeneic, as
      well as autologous, mixed lymphocyte reactions (MLRs), whereas freshly isolated
      neutrophils are completely unable to do so. In addition, neutrophil-derived DCs
      are at least 10,000 times more efficient in presenting soluble antigen to
      autologous T cells when compared to freshly isolated monocytes. Also, in
      functional terms, these neutrophil-derived DCs thus closely resemble "classical"
      DC populations.

PMID- 9529319
TI  - Activation mechanism of anticoagulant protein C in large blood vessels involving
      the endothelial cell protein C receptor.
AB  - Protein C is an important regulatory mechanism of blood coagulation. Protein C
      functions as an anticoagulant when converted to the active serine protease form
      on the endothelial cell surface. Thrombomodulin (TM), an endothelial cell surface
      receptor specific for thrombin, has been identified as an essential component for
      protein C activation. Although protein C can be activated directly by the
      thrombin-TM complex, the conversion is known as a relatively low-affinity
      reaction. Therefore, protein C activation has been believed to occur only in
      microcirculation. On the other hand, we have identified and cloned a novel
      endothelial cell surface receptor (EPCR) that is capable of high-affinity binding
      of protein C and activated protein C. In this study, we demonstrate the
      constitutive, endothelial cell-specific expression of EPCR in vivo. Abundant
      expression was particularly detected in the aorta and large arteries. In vitro
      cultured, arterial endothelial cells were also found to express abundant EPCR and
      were capable of promoting significant levels of protein C activation. EPCR was
      found to greatly accelerate protein C activation by examining functional activity
      in transfected cell lines expressing EPCR and/or TM. EPCR decreased the
      dissociation constant and increased the maximum velocity for protein C activation
      mediated by the thrombin-TM complex. By these mechanisms, EPCR appears to enable
      significant levels of protein C activation in large vessels. These results
      suggest that the protein C anticoagulation pathway is important for the
      regulation of blood coagulation not only in microvessels but also in large
      vessels.

PMID- 9529320
TI  - Murine cytomegalovirus inhibits interferon gamma-induced antigen presentation to
      CD4 T cells by macrophages via regulation of expression of major
      histocompatibility complex class II-associated genes.
AB  - CD4 T cells and interferon gamma (IFN-gamma) are required for clearance of murine
      cytomegalovirus (MCMV) infection from the salivary gland in a process taking
      weeks to months. To explain the inefficiency of salivary gland clearance we
      hypothesized that MCMV interferes with IFN-gamma induced antigen presentation to
      CD4 T cells. MCMV infection inhibited IFN-gamma-induced presentation of major
      histocompatibility complex (MHC) class II associated peptide antigen by
      differentiated bone marrow macrophages (BMMphis) to a T cell hybridoma via
      impairment of MHC class II cell surface expression. This effect was independent
      of IFN-alpha/beta induction by MCMV infection, and required direct infection of
      the BMMphis with live virus. Inhibition of MHC class II cell surface expression
      was associated with a six- to eightfold reduction in IFN-gamma induced IAb mRNA
      levels, and comparable decreases in IFN-gamma induced expression of invariant
      chain (Ii), H-2Ma, and H-2Mb mRNAs. Steady state levels of several constitutive
      host mRNAs, including beta-actin, cyclophilin, and CD45 were not significantly
      decreased by MCMV infection, ruling out a general effect of MCMV infection on
      mRNA levels. MCMV effects were specific to certain MHC genes since IFN-gamma
      induced transporter associated with antigen presentation (TAP)2 mRNA levels were
      minimally altered in infected cells. Analysis of early upstream events in the IFN
      gamma signaling pathway revealed that MCMV did not affect activation and nuclear
      translocation of STAT1alpha, and had minor effects on the early induction of IRF
      1 mRNA and protein. We conclude that MCMV infection interferes with IFN-gamma
      mediated induction of specific MHC genes and the Ii at a stage subsequent to
      STAT1alpha activation and nuclear translocation. This impairs antigen
      presentation to CD4 T cells, and may contribute to the capacity of MCMV to spread
      and persist within the infected host.

PMID- 9529321
TI  - alpha/beta-T cell receptor (TCR)+CD4-CD8- (NKT) thymocytes prevent insulin
      dependent diabetes mellitus in nonobese diabetic (NOD)/Lt mice by the influence
      of interleukin (IL)-4 and/or IL-10.
AB  - We have previously shown that nonobese diabetic (NOD) mice are selectively
      deficient in alpha/beta-T cell receptor (TCR)+CD4-CD8- NKT cells, a defect that
      may contribute to their susceptibility to the spontaneous development of insulin
      dependent diabetes mellitus (IDDM). The role of NKT cells in protection from IDDM
      in NOD mice was studied by the infusion of thymocyte subsets into young female
      NOD mice. A single intravenous injection of 10(6) CD4-/lowCD8- or CD4-CD8-
      thymocytes from female (BALB/c x NOD)F1 donors protected intact NOD mice from the
      spontaneous onset of clinical IDDM. Insulitis was still present in some recipient
      mice, although the cell infiltrates were principally periductal and periislet,
      rather than the intraislet pattern characteristic of insulitis in unmanipulated
      NOD mice. Protection was not associated with the induction of "allogenic
      tolerance" or systemic autoimmunity. Accelerated IDDM occurs after injection of
      splenocytes from NOD donors into irradiated adult NOD recipients. When alpha/beta
      TCR+ and alpha/beta-TCR- subsets of CD4-CD8- thymocytes were transferred with
      diabetogenic splenocytes and compared for their ability to prevent the
      development of IDDM in irradiated adult recipients, only the alpha/beta-TCR+
      population was protective, confirming that NKT cells were responsible for this
      activity. The protective effect in the induced model of IDDM was neutralized by
      anti-IL-4 and anti-IL-10 monoclonal antibodies in vivo, indicating a role for at
      least one of these cytokines in NKT cell-mediated protection. These results have
      significant implications for the pathogenesis and potential prevention of IDDM in
      humans.

PMID- 9529322
TI  - Ca2+ signaling modulates cytolytic T lymphocyte effector functions.
AB  - Cytolytic T cells use two mechanisms to kill virally infected cells, tumor cells,
      or other potentially autoreactive T cells in short-term in vitro assays. The
      perforin/granule exocytosis mechanism uses preformed cytolytic granules that are
      delivered to the target cell to induce apoptosis and eventual lysis. FasL/Fas
      (CD95 ligand/CD95)-mediated cytolysis requires de novo protein synthesis of FasL
      by the CTL and the presence of the death receptor Fas on the target cell to
      induce apoptosis. Using a CD8(+) CTL clone that kills via both the
      perforin/granule exocytosis and FasL/Fas mechanisms, and a clone that kills via
      the FasL/Fas mechanism only, we have examined the requirement of intra- and
      extracellular Ca2+ in TCR-triggered cytolytic effector function. These two
      clones, a panel of Ca2+ antagonists, and agonists were used to determine that a
      large biphasic increase in intracellular calcium concentration, characterized by
      release of Ca2+ from intracellular stores followed by a sustained influx of
      extracellular Ca2+, is required for perforin/granule exocytosis. Only the
      sustained influx of extracellular Ca2+ is required for FasL induction and
      killing. Thapsigargin, at low concentrations, induces this small but sustained
      increase in [Ca2+]i and selectively induces FasL/Fas-mediated cytolysis but not
      granule exocytosis. These results further define the role of Ca2+ in perforin and
      FasL/Fas killing and demonstrate that differential Ca2+ signaling can modulate T
      cell effector functions.

PMID- 9529323
TI  - Yersinia enterocolitica impairs activation of transcription factor NF-kappaB:
      involvement in the induction of programmed cell death and in the suppression of
      the macrophage tumor necrosis factor alpha production.
AB  - In this study, we investigated the activity of transcription factor NF-kappaB in
      macrophages infected with Yersinia enterocolitica. Although triggering initially
      a weak NF-kappaB signal, Y. enterocolitica inhibited NF-kappaB activation in
      murine J774A.1 and peritoneal macrophages within 60 to 90 min. Simultaneously, Y.
      enterocolitica prevented prolonged degradation of the inhibitory proteins IkappaB
      alpha and IkappaB-beta observed by treatment with lipopolysaccharide (LPS) or
      nonvirulent, plasmid-cured yersiniae. Analysis of different Y. enterocolitica
      mutants revealed a striking correlation between the abilities of these strains to
      inhibit NF-kappaB and to suppress the tumor necrosis factor alpha (TNF-alpha)
      production as well as to trigger macrophage apoptosis. When NF-kappaB activation
      was prevented by the proteasome inhibitor MG-132, nonvirulent yersiniae as well
      as LPS became able to trigger J774A.1 cell apoptosis and inhibition of the TNF
      alpha secretion. Y. enterocolitica also impaired the activity of NF-kappaB in
      epithelial HeLa cells. Although neither Y. enterocolitica nor TNF-alpha could
      induce HeLa cell apoptosis alone, TNF-alpha provoked apoptosis when activation of
      NF-kappaB was inhibited by Yersinia infection or by the proteasome inhibitor MG
      132. Together, these data demonstrate that Y. enterocolitica suppresses cellular
      activation of NF-kappaB, which inhibits TNF-alpha release and triggers apoptosis
      in macrophages. Our results also suggest that Yersinia infection confers
      susceptibility to programmed cell death to other cell types, provided that the
      appropriate death signal is delivered.

PMID- 9529324
TI  - Transgene expression of bcl-xL permits anti-immunoglobulin (Ig)-induced
      proliferation in xid B cells.
AB  - Mutations in the tyrosine kinase, Btk, result in a mild immunodeficiency in mice
      (xid). While B lymphocytes from xid mice do not proliferate to anti
      immunoglobulin (Ig), we show here induction of the complete complement of cell
      cycle regulatory molecules, though the level of induction is about half that
      detected in normal B cells. Cell cycle analysis reveals that anti-Ig stimulated
      xid B cells enter S phase, but fail to complete the cell cycle, exhibiting a high
      rate of apoptosis. This correlated with a decreased ability to induce the anti
      apoptosis regulatory protein, Bcl-xL. Ectopic expression of Bcl-xL in xid B cells
      permitted anti-Ig induced cell cycle progression demonstrating dual requirements
      for induction of anti-apoptotic proteins plus cell cycle regulatory proteins
      during antigen receptor mediated proliferation. Furthermore, our results link one
      of the immunodeficient traits caused by mutant Btk with the failure to properly
      regulate Bcl-xL.

PMID- 9529325
TI  - T cell development in mice lacking all T cell receptor zeta family members (Zeta,
      eta, and FcepsilonRIgamma).
AB  - The zeta family includes zeta, eta, and FcepsilonRIgamma (Fcgamma). Dimers of the
      zeta family proteins function as signal transducing subunits of the T cell
      antigen receptor (TCR), the pre-TCR, and a subset of Fc receptors. In mice
      lacking zeta/eta chains, T cell development is impaired, yet low numbers of CD4+
      and CD8+ T cells develop. This finding suggests either that pre-TCR and TCR
      complexes lacking a zeta family dimer can promote T cell maturation, or that in
      the absence of zeta/eta, Fcgamma serves as a subunit in TCR complexes. To
      elucidate the role of zeta family dimers in T cell development, we generated mice
      lacking expression of all of these proteins and compared their phenotype to mice
      lacking only zeta/eta or Fcgamma. The data reveal that surface complexes that are
      expressed in the absence of zeta family dimers are capable of transducing signals
      required for alpha/beta-T cell development. Strikingly, T cells generated in both
      zeta/eta-/- and zeta/eta-/--Fcgamma-/- mice exhibit a memory phenotype and
      elaborate interferon gamma. Finally, examination of different T cell populations
      reveals that zeta/eta and Fcgamma have distinct expression patterns that
      correlate with their thymus dependency. A possible function for the differential
      expression of zeta family proteins may be to impart distinctive signaling
      properties to TCR complexes expressed on specific T cell populations.

PMID- 9529326
TI  - Human immunodeficiency virus type 1 Vpr is a positive regulator of viral
      transcription and infectivity in primary human macrophages.
AB  - It is currently well established that HIV-1 Vpr augments viral replication in
      primary human macrophages. In its virion-associated form, Vpr has been suggested
      to aid efficient translocation of the proviral DNA into the cell nucleus.
      Although Vpr growth-arrests dividing T cells, the relevance of this biological
      activity in nondividing macrophages is unclear. Here we use Vpr-mutants to
      demonstrate that the molecular determinants involved in G2-arresting T cells are
      also involved in increasing viral transcription in macrophages, even though these
      cells are refractive to the diploid DNA status typical of G2 phase. Our results
      suggest that the two phenotypes, namely the nuclear localization and the G2
      arrest activity of the protein, segregate functionally among the late and early
      functions of Vpr. The nuclear localization property of Vpr correlates with its
      ability to effectively target the proviral DNA to the cell nucleus early in the
      infection, whereas the G2-arrest phenotype correlates with its ability to
      activate viral transcription after establishment of an infection. These two
      functions may render Vpr's role essential and not accessory under infection
      conditions that closely mimic the in vivo situation, that is, primary cells being
      infected at low viral inputs.

PMID- 9529327
TI  - HIV-1 directly kills CD4+ T cells by a Fas-independent mechanism.
AB  - The mechanism by which HIV-1 induces CD4(+) T cell death is not known. A
      fundamental issue is whether HIV-1 primarily induces direct killing of infected
      cells or indirectly causes death of uninfected bystander cells. This question was
      studied using a reporter virus system in which infected cells are marked with the
      cell surface protein placental alkaline phosphatase (PLAP). Infection by HIV-PLAP
      of peripheral blood mononuclear cells (PBMCs) and T cell lines leads to rapid
      depletion of CD4(+) T cells and induction of apoptosis. The great majority of HIV
      induced T cell death in vitro involves direct loss of infected cells rather than
      indirect effects on uninfected bystander cells. Because of its proposed role in
      HIV-induced cell death, we also examined the Fas (CD95/Apo1) pathway in killing
      of T cells by HIV-1. Infected PBMCs or CEM cells display no increase in surface
      Fas relative to uninfected cells. In addition, HIV-1 kills CEM and Jurkat T cells
      in the presence of a caspase inhibitor that completely blocks Fas-mediated
      apoptosis. HIV-1 also depletes CD4+ T cells in PBMCs from patients who have a
      genetically defective Fas pathway. These results suggest that HIV-1 induces
      direct apoptosis of infected cells and kills T cells by a Fas-independent
      mechanism.

PMID- 9529328
TI  - Mucosal adjuvanticity and immunogenicity of LTR72, a novel mutant of Escherichia
      coli heat-labile enterotoxin with partial knockout of ADP-ribosyltransferase
      activity.
AB  - Heat-labile Escherichia coli enterotoxin (LT) has the innate property of being a
      strong mucosal immunogen and adjuvant. In the attempt to reduce toxicity and
      maintain the useful immunological properties, several LT mutants have been
      produced. Some of these are promising mucosal adjuvants. However, so far, only
      those that were still toxic maintained full adjuvanticity. In this paper we
      describe a novel LT mutant with greatly reduced toxicity that maintains most of
      the adjuvanticity. The new mutant (LTR72), that contains a substitution Ala -->
      Arg in position 72 of the A subunit, showed only 0.6% of the LT enzymatic
      activity, was 100,000-fold less toxic than wild-type LT in Y1 cells in vitro, and
      was at least 20 times less effective than wild-type LT in the rabbit ileal loop
      assay in vivo. At a dose of 1 microg, LTR72 exhibited a mucosal adjuvanticity,
      similar to that observed with wild-type LT, better than that induced by the
      nontoxic, enzymatically inactive LTK63 mutant, and much greater than that of the
      recombinant B subunit. This trend was consistent for both the amounts and
      kinetics of the antibody induced, and priming of antigen-specific T lymphocytes.
      The data suggest that the innate high adjuvanticity of LT derives from the
      independent contribution of the nontoxic AB complex and the enzymatic activity.
      LTR72 optimizes the use of both properties: the enzymatic activity for which
      traces are enough, and the nontoxic AB complex, the effect of which is dose
      dependent. In fact, in dose-response experiments in mice, 20 microg of LTR72 were
      a stronger mucosal adjuvant than wild-type LT. This suggests that LTR72 may be an
      excellent candidate to be tested in clinical trials.

PMID- 9529329
TI  - Activated complement component 3 (C3) is required for ultraviolet induction of
      immunosuppression and antigenic tolerance.
AB  - Complement component 3 (C3), a critical regulator of innate immunity, may also
      play a role in the regulation of cognate immunity, such as contact sensitivity
      responses. Because ultraviolet (UV) radiation also activates C3 in the skin, we
      determined whether the immunosuppressed state that results when a contact
      sensitizer is applied through UVB-exposed skin requires the presence and
      activation of C3. This question was addressed through the use of C3-deficient
      mice, blockade of C3 cleavage to C3b, and accelerated degradation of iC3b by
      soluble complement receptor 1 (sCR1). Both C3-modulated systems totally reversed
      the failure to induce a contact sensitivity response to dinitrofluorobenzene
      (DNFB) upon primary sensitization at the UV-exposed site, as well as immunologic
      tolerance to a second DNFB immunization through normal skin. Treatment with sCR1
      reduced the infiltration of CD11b+ leukocytes into the epidermis and dermis of UV
      irradiated skin but did not reverse the UV-induced depletion of epidermal class
      II MHC+CD11blo Langerhans cells. These data, taken together with previous results
      showing abrogation of locally induced UV immunosuppression by in vivo anti-CD11b
      treatment, suggest a novel mechanism by which ligation of the leukocyte beta2
      integrin, CD11b, by iC3b molecules formed from C3 activation in UV-exposed skin,
      modifies cutaneous CD11b+ cells such that skin antigen-presenting cells are
      unable to sensitize in a primary immune response, but actively induce antigenic
      tolerance.

PMID- 9529330
TI  - Productive infection of neonatal CD8+ T lymphocytes by HIV-1.
AB  - CD8+ T lymphocytes confer significant but ultimately insufficient protection
      against HIV infection. Here we report that activated neonatal CD8+ T cells can be
      productively infected in vitro by macrophage-tropic (M-tropic) HIV-1 isolates,
      which are responsible for disease transmission, whereas they are resistant to T
      cell-tropic (T-tropic) HIV strains. Physiological activation of CD8-alpha/beta+
      CD4- T cell receptor-alpha/beta+ neonatal T cells, including activation by
      allogeneic dendritic cells, induces the accumulation of CD4 messenger RNA and the
      expression of CD4 Ag on the cell surface. The large majority of anti-CD3/B7.1
      activated cord blood CD8+ T cells coexpress CD4, the primary HIV receptor, as
      well as CCR5 and CXCR4, the coreceptors used by M- and T-tropic HIV-1 strains,
      respectively, to enter target cells. These findings are relevant to the rapid
      progression of neonatal HIV infection. Infection of primary HIV-specific CD8+ T
      cells may compromise their survival and thus significantly contribute to the
      failure of the immune system to control the infection. Furthermore, these results
      indicate a previously unsuspected level of plasticity in the neonatal immune
      system in the regulation of CD4 expression by costimulation.

PMID- 9529331
TI  - DNA as an adjuvant: capacity of insect DNA and synthetic oligodeoxynucleotides to
      augment T cell responses to specific antigen.
AB  - How strong adjuvants such as complete Freund's adjuvant (CFA) promote T cell
      priming to protein antigens in vivo is still unclear. Since the unmethylated CpG
      motifs in DNA of bacteria and other nonvertebrates are stimulatory for B cells
      and antigen-presenting cells, the strong adjuvanticity of CFA could be
      attributed, at least in part, to the presence of dead bacteria, i.e., a source of
      stimulatory DNA. In support of this possibility, evidence is presented that
      insect DNA in mineral oil has even stronger adjuvant activity than CFA by a
      number of parameters. Synthetic oligodeoxynucleotides (ODNs) containing
      unmethylated CpG motifs mimic the effects of insect DNA and, even in soluble
      form, ODNs markedly potentiate clonal expansion of T cell receptor transgenic T
      cells responding to specific peptide.

PMID- 9529332
TI  - CD28-independent induction of T helper cells and immunoglobulin class switches
      requires costimulation by the heat-stable antigen.
AB  - It is well established that B7-CD28/CTLA4 interactions play an important role in
      the induction of T helper cells for T-dependent antibody responses. However,
      targeted mutation of CD28 does not significantly affect production of IgG and
      activation of CD4 T helper cells in response to infections by some viruses and
      nematode parasites. To test whether the CD28-independent induction of Ig class
      switches requires costimulation by the heat-stable antigen (HSA), we compared T
      helper cell induction and antibody response in mice deficient for either HSA,
      CD28, or both genes. We found that after immunization with KLH-DNP, mice
      deficient for both CD28 and HSA lack DNP-specific IgA and all subtypes of IgG.
      This deficiency corresponds to a reduced number of effector helper T cells that
      rapidly produce IL-2, IL-4, and IFN-gamma after in vitro stimulation with carrier
      antigen KLH. In contrast, priming of T helper cells and Ig class switch are
      normal in mice deficient with either HSA or CD28 alone. IgM responses are not
      affected by any of these targeted mutations. These results demonstrate that CD28
      independent induction of T helper cells and Ig class-switches requires
      costimulation by the HSA.

PMID- 9529333
TI  - Molecular cloning of the cDNA encoding pp36, a tyrosine-phosphorylated adaptor
      protein selectively expressed by T cells and natural killer cells.
AB  - Activation of T and natural killer (NK) cells leads to the tyrosine
      phosphorylation of pp36 and to its association with several signaling molecules,
      including phospholipase Cgamma-1 and Grb2. Microsequencing of peptides derived
      from purified rat pp36 protein led to the cloning, in rat and man, of cDNA
      encoding a T- and NK cell-specific protein with several putative Src homology 2
      domain-binding motifs. A rabbit antiserum directed against a peptide sequence
      from the cloned rat molecule recognized tyrosine phosphorylated pp36 from
      pervanadate-treated rat thymocytes. When expressed in 293T human fibroblast cells
      and tyrosine-phosphorylated, pp36 associated with phospholipase Cgamma-1 and
      Grb2. Studies with GST-Grb2 fusion proteins demonstrated that the association was
      specific for the Src homology 2 domain of Grb-2. Molecular cloning of the gene
      encoding pp36 should facilitate studies examining the role of this adaptor
      protein in proximal signaling events during T and NK cell activation.

PMID- 9529334
TI  - OA1 mutations and deletions in X-linked ocular albinism.
AB  - X-linked ocular albinism (OA1), Nettleship-Falls type, is characterized by
      decreased ocular pigmentation, foveal hypoplasia, nystagmus, photodysphoria, and
      reduced visual acuity. Affected males usually demonstrate melanin macroglobules
      on skin biopsy. We now report results of deletion and mutation screening of the
      full-length OA1 gene in 29 unrelated North American and Australian X-linked
      ocular albinism (OA) probands, including five with additional, nonocular
      phenotypic abnormalities (Schnur et al. 1994). We detected 13 intragenic gene
      deletions, including 3 of exon 1, 2 of exon 2, 2 of exon 4, and 6 others, which
      span exons 2-8. Eight new missense mutations were identified, which cluster
      within exons 1, 2, 3, and 6 in conserved and/or putative transmembrane domains of
      the protein. There was also a splice acceptor-site mutation, a nonsense mutation,
      a single base deletion, and a previously reported 17-bp exon 1 deletion. All
      patients with nonocular phenotypic abnormalities had detectable mutations. In
      summary, 26 (approximately 90%) of 29 probands had detectable alterations of OA1,
      thus confirming that OA1 is the major locus for X-linked OA.

PMID- 9529335
TI  - Molecular cytogenetic evidence for a common breakpoint in the largest inverted
      duplications of chromosome 15.
AB  - Chromosomes from 20 patients were used to delineate the breakpoints of inverted
      duplications of chromosome 15 (inv dup[15]) that include the Prader-Willi
      syndrome/Angelman syndrome (PWS/AS) chromosomal region (15q11-q13). YAC and
      cosmid clones from 15q11-q14 were used for FISH analysis, to detect the presence
      or absence of material on each inv dup(15). We describe two types of inv dup(15):
      those that break between D15S12 and D15S24, near the distal boundary of the
      PWS/AS chromosomal region, and those that share a breakpoint immediately proximal
      to D15S1010. Among the latter group, no breakpoint heterogeneity could be
      detected with the available probes, and one YAC (810f11) showed a reduced signal
      on each inv dup(15), compared with that on normal chromosomes 15. The lack of
      breakpoint heterogeneity may be the result of a U-type exchange involving
      particular sequences on either homologous chromosomes or sister chromatids.
      Parent-of-origin studies revealed that, in all the cases analyzed, the inv
      dup(15) was maternal in origin.

PMID- 9529338
TI  - Using neural networks as an aid in the determination of disease status:
      comparison of clinical diagnosis to neural-network predictions in a pedigree with
      autosomal dominant limb-girdle muscular dystrophy.
AB  - Studies of the genetics of certain inherited diseases require expertise in the
      determination of disease status even for single-locus traits. For example, in the
      diagnosis of autosomal dominant limb-girdle muscular dystrophy (LGMD1A), it is
      not always possible to make a clear-cut determination of disease, because of
      variability in the diagnostic criteria, age at onset, and differential
      presentation of disease. Mapping such diseases is greatly simplified if the data
      present a homogeneous genetic trait and if disease status can be reliably
      determined. Here, we present an approach to determination of disease status,
      using methods of artificial neural-network analysis. The method entails
      "training" an artificial neural network, with input facts (based on diagnostic
      criteria) and related results (based on disease diagnosis). The network contains
      weight factors connecting input "neurons" to output "neurons," and these
      connections are adjusted until the network can reliably produce the appropriate
      outputs for the given input facts. The trained network can be "tested" with a
      second set of facts, in which the outcomes are known but not provided to the
      network, to see how well the training has worked. The method was applied to
      members of a pedigree with LGMD1A, now mapped to chromosome 5q. We used
      diagnostic criteria and disease status to train a neural network to classify
      individuals as "affected" or "not affected." The trained network reproduced the
      disease diagnosis of all individuals of known phenotype, with 98% reliability.
      This approach defined an appropriate choice of clinical factors for determination
      of disease status. Additionally, it provided insight into disease classification
      of those considered to have an "unknown" phenotype on the basis of standard
      clinical diagnostic methods.

PMID- 9529339
TI  - Evidence for genetic heterogeneity in X-linked congenital stationary night
      blindness.
AB  - X-linked congenital stationary night blindness (CSNB) is a nonprogressive retinal
      disorder characterized by disturbed or absent night vision; its clinical features
      may also include myopia, nystagmus, and impaired visual acuity. X-linked CSNB is
      clinically heterogeneous, and it may also be genetically heterogeneous. We have
      studied 32 families with X-linked CSNB, including 11 families with the complete
      form of CSNB and 21 families with the incomplete form of CSNB, to identify
      genetic-recombination events that would refine the location of the disease genes.
      Critical recombination events in the set of families with complete CSNB have
      localized a disease gene to the region between DXS556 and DXS8083, in Xp11.4
      p11.3. Critical recombination events in the set of families with incomplete CSNB
      have localized a disease gene to the region between DXS722 and DXS8023, in
      Xp11.23. Further analysis of the incomplete-CSNB families, by means of disease
      associated-haplotype construction, identified 17 families, of apparent Mennonite
      ancestry, that share portions of an ancestral chromosome. Results of this
      analysis refined the location of the gene for incomplete CSNB to the region
      between DXS722 and DXS255, a distance of 1.2 Mb. Genetic and clinical analyses of
      this set of 32 families with X-linked CSNB, together with the family studies
      reported in the literature, strongly suggest that two loci, one for complete
      (CSNB1) and one for incomplete (CSNB2) X-linked CSNB, can account for all
      reported mapping information.

PMID- 9529341
TI  - The quantitative LOD score: test statistic and sample size for exclusion and
      linkage of quantitative traits in human sibships.
AB  - We present a test statistic, the quantitative LOD (QLOD) score, for the testing
      of both linkage and exclusion of quantitative-trait loci in randomly selected
      human sibships. As with the traditional LOD score, the boundary values of 3, for
      linkage, and -2, for exclusion, can be used for the QLOD score. We investigated
      the sample sizes required for inferring exclusion and linkage, for various
      combinations of linked genetic variance, total heritability, recombination
      distance, and sibship size, using fixed-size sampling. The sample sizes required
      for both linkage and exclusion were not qualitatively different and depended on
      the percentage of variance being linked or excluded and on the total genetic
      variance. Information regarding linkage and exclusion in sibships larger than
      size 2 increased as approximately all possible pairs n(n-1)/2 up to sibships of
      size 6. Increasing the recombination (theta) distance between the marker and the
      trait loci reduced empirically the power for both linkage and exclusion, as a
      function of approximately (1-2theta)4.

PMID- 9529340
TI  - DAX1 mutations map to putative structural domains in a deduced three-dimensional
      model.
AB  - The DAX1 protein is an orphan nuclear hormone receptor based on sequence
      similarity in the putative ligand-binding domain (LBD). DAX1 mutations result in
      X-linked adrenal hypoplasia congenita (AHC). Our objective was to identify DAX1
      mutations in a series of families, to determine the types of mutations resulting
      in AHC and to locate single-amino-acid changes in a DAX1 structural model. The 14
      new mutations identified among our 17 families with AHC brought the total number
      of families with AHC to 48 and the number of reported mutations to 42; 1 family
      showed gonadal mosaicism. These mutations included 23 frameshift, 12 nonsense,
      and six missense mutations and one single-codon deletion. We mapped the seven
      single-amino-acid changes to a homology model constructed by use of the three
      dimensional crystal structures of the thyroid-hormone receptor and retinoid X
      receptor alpha. All single-amino-acid changes mapped to the C-terminal half of
      the DAX1 protein, in the conserved hydrophobic core of the putative LBD, and none
      affected residues expected to interact directly with a ligand. We conclude that
      most genetic alterations in DAX1 are frameshift or nonsense mutations and
      speculate that the codon deletion and missense mutations give insight into the
      structure and function of DAX1.

PMID- 9529342
TI  - Determinism and mass-media portrayals of genetics.
AB  - Scholars have expressed concern that the introduction of substantial coverage of
      "medical genetics" in the mass media during the past 2 decades represents an
      increase in biological determinism in public discourse. To test this contention,
      we analyzed the contents of a randomly selected, structured sample of American
      public newspapers (n=250) and magazines (n=722) published during 1919-95. Three
      coders, using three measures, all with intercoder reliability >85%, were
      employed. Results indicate that the introduction of the discourse of medical
      genetics is correlated with both a statistically significant decrease in the
      degree to which articles attribute human characteristics to genetic causes
      (P<.001) and a statistically significant increase in the differentiation of
      attributions to genetic and other causes among various conditions or outcomes
      (P<. 016). There has been no statistically significant change in the relative
      proportions of physical phenomena attributed to genetic causes, but there has
      been a statistically significant decrease in the number of articles assigning
      genetic causes to mental (P<.002) and behavioral (P<.000) characteristics. These
      results suggest that the current discourse of medical genetics is not accurately
      described as more biologically deterministic than its antecedents.

PMID- 9529343
TI  - No evidence for significant linkage between bipolar affective disorder and
      chromosome 18 pericentromeric markers in a large series of multiplex extended
      pedigrees.
AB  - Bipolar affective disorder (BP) is a major neuropsychiatric disorder with high
      heritability and complex inheritance. Previously reported linkage between BP and
      DNA markers in the pericentromeric region of chromosome 18, with a parent-of
      origin effect (linkage was present in pedigrees with paternal transmission and
      absent in pedigrees with exclusive maternal inheritance), has been a focus of
      interest in human genetics. We reexamined the evidence in one of the largest
      samples reported to date (1,013 genotyped individuals in 53 unilineal multiplex
      pedigrees), using 10 highly polymorphic markers and a range of parametric and
      nonparametric analyses. There was no evidence for significant linkage between BP
      and chromosome 18 pericentromeric markers in the sample as a whole, nor was there
      evidence for significant parent-of-origin effect (pedigrees with paternal
      transmission were not differentially linked to the implicated chromosomal
      region). Two-point LOD scores and single-locus sib-pair results gave some support
      for suggestive linkage, but this was not substantiated by multilocus analysis,
      and the results were further tempered by multiple test effects. We conclude that
      there is no compelling evidence for linkage between BP and chromosome 18
      pericentromeric markers in this sample.

PMID- 9529344
TI  - Genetic mapping refines DFNB3 to 17p11.2, suggests multiple alleles of DFNB3, and
      supports homology to the mouse model shaker-2.
AB  - The nonsyndromic congenital recessive deafness gene, DFNB3, first identified in
      Bengkala, Bali, was mapped to a approximately 12-cM interval on chromosome 17.
      New short tandem repeats (STRs) and additional DNA samples were used to identify
      recombinants that constrain the DFNB3 interval to less, similar6 cM on 17p11.2.
      Affected individuals from Bengkala and affected members of a family with
      hereditary deafness who were from Bila, a village neighboring Bengkala, were
      homozygous for the same alleles for six adjacent STRs in the DFNB3 region and
      were heterozygous for other distal markers, thus limiting DFNB3 to an
      approximately 3-cM interval. Nonsyndromic deafness segregating in two unrelated
      consanguineous Indian families, M21 and I-1924, were also linked to the DFNB3
      region. Haplotype analysis indicates that the DFNB3 mutations in the three
      pedigrees most likely arose independently and suggests that DFNB3 makes a
      significant contribution to hereditary deafness worldwide. On the basis of
      conserved synteny, mouse deafness mutations shaker-2 (sh2) and sh2J are proposed
      as models of DFNB3. Genetic mapping has refined sh2 to a 0.6-cM interval of
      chromosome 11. Three homologous genes map within the sh2 and DFNB3 intervals,
      suggesting that sh2 is the homologue of DFNB3.

PMID- 9529346
TI  - The African origin of the common mutation in African American patients with
      glycogen-storage disease type II.

PMID- 9529345
TI  - Genetic association mapping based on discordant sib pairs: the discordant-alleles
      test.
AB  - Family-based tests of association provide the opportunity to test for an
      association between a disease and a genetic marker. Such tests avoid false
      positive results produced by population stratification, so that evidence for
      association may be interpreted as evidence for linkage or causation. Several
      methods that use family-based controls have been proposed, including the
      haplotype relative risk, the transmission-disequilibrium test, and affected
      family-based controls. However, because these methods require genotypes on
      affected individuals and their parents, they are not ideally suited to the study
      of late-onset diseases. In this paper, we develop several family-based tests of
      association that use discordant sib pairs (DSPs) in which one sib is affected
      with a disease and the other sib is not. These tests are based on statistics that
      compare counts of alleles or genotypes or that test for symmetry in tables of
      alleles or genotypes. We describe the use of a permutation framework to assess
      the significance of these statistics. These DSP-based tests provide the same
      general advantages as parent-offspring trio-based tests, while being applicable
      to essentially any disease; they may also be tailored to particular hypotheses
      regarding the genetic model. We compare the statistical properties of our DSP
      based tests by computer simulation and illustrate their use with an application
      to Alzheimer disease and the apolipoprotein E polymorphism. Our results suggest
      that the discordant-alleles test, which compares the numbers of nonmatching
      alleles in DSPs, is the most powerful of the tests we considered, for a wide
      class of disease models and marker types. Finally, we discuss advantages and
      disadvantages of the DSP design for genetic association mapping.

PMID- 9529347
TI  - Marshall syndrome associated with a splicing defect at the COL11A1 locus.
AB  - Marshall syndrome is a rare, autosomal dominant skeletal dysplasia that is
      phenotypically similar to the more common disorder Stickler syndrome. For a large
      kindred with Marshall syndrome, we demonstrate a splice-donor-site mutation in
      the COL11A1 gene that cosegregates with the phenotype. The G+1-->A transition
      causes in-frame skipping of a 54-bp exon and deletes amino acids 726-743 from the
      major triple-helical domain of the alpha1(XI) collagen polypeptide. The data
      support the hypothesis that the alpha1(XI) collagen polypeptide has an important
      role in skeletal morphogenesis that extends beyond its contribution to structural
      integrity of the cartilage extracellular matrix. Our results also demonstrate
      allelism of Marshall syndrome with the subset of Stickler syndrome families
      associated with COL11A1 mutations.

PMID- 9529349
TI  - HLA and mate choice.

PMID- 9529350
TI  - Linkage thresholds for two-stage genome scans.

PMID- 9529348
TI  - Mutations in the liver glycogen phosphorylase gene (PYGL) underlying glycogenosis
      type VI.
AB  - Deficiency of glycogen phosphorylase in the liver gives rise to glycogen-storage
      disease type VI (Hers disease; MIM 232700). We report the identification of the
      first mutations in PYGL, the gene encoding the liver isoform of glycogen
      phosphorylase, in three patients with Hers disease. These are two splice-site
      mutations and two missense mutations. A mutation of the 5' splice-site consensus
      of intron 14 causes the retention of intron 14 and the utilization of two
      illegitimate 5' splice sites, whereas a mutation of the 3' splice-site consensus
      of intron 4 causes the skipping of exon 5. Two missense mutations, N338S and
      N376K, both cause nonconservative replacements of amino acids that are absolutely
      conserved even in yeast and bacterial phosphorylases. We also report corrections
      of the PYGL coding sequence, sequence polymorphisms, and a partial PYGL gene
      structure with introns in the same positions as in PYGM, the gene of the muscle
      isoform of phosphorylase. Our findings demonstrate that PYGL mutations cause Hers
      disease, and they may improve laboratory diagnosis of deficiencies of the liver
      phosphorylase system.

PMID- 9529351
TI  - Gene localization for an autosomal dominant familial periodic fever to 12p13.
AB  - We report gene localization in a family with a benign autosomal dominant familial
      periodic fever (FPF) syndrome characterized by recurrent fever associated with
      abdominal pain. The clinical features are similar to the disorder previously
      described as familial Hibernian fever, and they differ from familial
      Mediterranean fever (FMF) in that FPF episodes usually do not respond to
      colchicine and FPF is not associated with amyloidosis. Frequent recombination
      with the marker D16S2622, <1 Mb from FMF, at 16p13.3, excluded allelism between
      these clinically similar conditions. Subsequently, a semiautomated genome search
      detected linkage of FMF to a cluster of markers at 12p13, with a multipoint LOD
      score of 6.14 at D12S356. If penetrance of 90% is assumed, the FPF gene maps to a
      19-cM interval between D12S314 and D12S364; however, if complete penetrance is
      assumed, then FPF maps to a 9-cM region between D12S314 and D12S1695. This
      interval includes the dentatorubropallidoluysian atrophy locus, which, with FPF,
      gave a maximum two-point LOD score of 3.7 at a recombination fraction of 0. This
      is the first of the periodic-fever genes, other than FMF, to be mapped.
      Positional candidate genes may now be selected for mutation analysis to determine
      the molecular basis for FPF. Together with the recent identification of the
      defective gene in FMF, identification of a gene for FPF might provide new
      insights into the regulation of inflammatory responses.

PMID- 9529352
TI  - Refined genetic mapping of the darier locus to a <1-cM region of chromosome
      12q24.1, and construction of a complete, high-resolution P1 artificial
      chromosome/bacterial artificial chromosome contig of the critical region.
AB  - Darier disease (DD) (MIM 124200) is an autosomal dominant skin disorder
      characterized by loss of adhesion between epidermal cells and by abnormal
      keratinization. We present linkage analysis showing, in four families, key
      recombination events that refine the location of the DD locus on chromosome 12q23
      24.1 to a region of <1 cM. We have constructed a YAC/P1 artificial chromosome
      (PAC)/bacterial artificial chromosome (BAC)-based physical map that encompasses
      this refined DD region. The map consists of 35 YAC, 69 PAC, 16 BAC, and 2 cosmid
      clones that were ordered by mapping 54 anonymous sequence-tagged sites. The
      critical region is estimated to be 2.4 Mb in size, with an average marker
      resolution of 37.5 kb. The refinement of the critical interval excludes the
      ALDH2, RPL6, PTPN11, and OAS genes, as well as seven expressed sequence tags
      (ESTs) previously mapped in the DD region. The three known genes (ATP2A2, PPP1CC,
      and SCA2) and the 10 ESTs mapped within the critical region are not obvious
      candidates for the DD gene. Therefore, this detailed integrated physical,
      genetic, and partial transcript map provides an important resource for the
      isolation of the DD gene and, possibly, other disease genes.

PMID- 9529354
TI  - Polymorphic detection of a parthenogenetic maternal and double paternal
      contribution to a 46,XX/46,XY hermaphrodite.
AB  - True hermaphroditism in humans usually is associated with a 46,XX karyotype or
      with mosaicism in which admixtures of cells with an XX and an XY karyotype are
      seen. However, the mechanisms that cause such mosaicisms are poorly understood.
      To date, with rare exceptions, analyses of hermaphrodites have been limited
      mostly to cytogenetic investigations. In this report, we describe a 5-year-old
      patient with true hermaphroditism and a 46,XX/46,XY karyotype (ratio 38:12) in
      lymphocytes, suggesting involvement of two fertilization events. Microsatellite
      DNA polymorphisms distributed throughout the genome were analyzed, to investigate
      the origin of the cell lines concerned. The results are consistent with double
      paternal and single maternal genetic contributions. Possible mechanisms that
      would explain these findings are discussed. The most likely mechanism involves a
      single haploid ovum dividing parthenogenetically into two haploid ova, followed
      by double fertilization and fusion of the two zygotes into a single individual,
      at the early embryonic stage.

PMID- 9529353
TI  - Paternal uniparental disomy for chromosome 1 revealed by molecular analysis of a
      patient with pycnodysostosis.
AB  - Molecular analysis of a patient affected by the autosomal recessive skeletal
      dysplasia, pycnodysostosis (cathepsin K deficiency; MIM 265800), revealed
      homozygosity for a novel missense mutation (A277V). Since the A277V mutation was
      carried by the patient's father but not by his mother, who had two normal
      cathepsin K alleles, paternal uniparental disomy was suspected. Karyotyping of
      the patient and of both parents was normal, and high-resolution cytogenetic
      analyses of chromosome 1, to which cathepsin K is mapped, revealed no
      abnormalities. Evaluation of polymorphic DNA markers spanning chromosome 1
      demonstrated that the patient had inherited two paternal chromosome 1 homologues,
      whereas alleles for markers from other chromosomes were inherited in a Mendelian
      fashion. The patient was homoallelic for informative markers mapping near the
      chromosome 1 centromere, but he was heteroallelic for markers near both
      telomeres, establishing that the paternal uniparental disomy with partial
      isodisomy was caused by a meiosis II nondisjunction event. Phenotypically, the
      patient had normal birth height and weight, had normal psychomotor development at
      age 7 years, and had only the usual features of pycnodysostosis. This patient
      represents the first case of paternal uniparental disomy of chromosome 1 and
      provides conclusive evidence that paternally derived genes on human chromosome 1
      are not imprinted.

PMID- 9529355
TI  - Genetic linkage of hereditary gingival fibromatosis to chromosome 2p21.
AB  - Gingival fibromatosis is characterized by a slowly progressive benign enlargement
      of the oral gingival tissues. The condition results in the teeth being partially
      or totally engulfed by keratinized gingiva, causing aesthetic and functional
      problems. Both genetic and pharmacologically induced forms of gingival
      fibromatosis are known. The most common genetic form, hereditary gingival
      fibromatosis (HGF), is usually transmitted as an autosomal dominant trait,
      although sporadic cases are common and autosomal recessive inheritance has been
      reported. The genetic basis of gingival fibromatosis is unknown. We identified an
      extended family (n=32) segregating an autosomal dominant form of isolated
      gingival fibromatosis. Using a genomewide search strategy, we identified genetic
      linkage (Zmax=5.05, straight theta=.00) for the HGF phenotype to polymorphic
      markers in the genetic region of chromosome 2p21 bounded by the loci D2S1788 and
      D2S441. This is the first report of linkage for isolated HGF, and the findings
      have implications for identification of the underlying genetic basis of gingival
      fibromatosis.

PMID- 9529356
TI  - A PCR amplification method reveals instability of the dodecamer repeat in
      progressive myoclonus epilepsy (EPM1) and no correlation between the size of the
      repeat and age at onset.
AB  - Progressive myoclonus epilepsy of the Unverricht-Lundborg type (EPM1) is a rare,
      autosomal recessive disorder characterized by onset at age 6-16 years,
      generalized seizures, incapacitating myoclonus, and variable progression to
      cerebellar ataxia. The gene that causes EPM1, cystatin B, encodes a cysteine
      proteinase inhibitor. Only a minority of EPM1 patients carry a point mutation
      within the transcription unit. The majority of EPM1 alleles contain large
      expansions of a dodecamer repeat, CCC CGC CCC GCG, located upstream of the 5'
      transcription start site of the cystatin B gene; normal alleles contain two or
      three copies of this repeat. All EPM1 alleles with an expansion were resistant to
      standard PCR amplification. To precisely determine the size of the repeat in
      affected individuals, we developed a detection protocol involving PCR
      amplification and subsequent hybridization with an oligonucleotide containing the
      repeat. The largest detected expansion was approximately 75 copies; the smallest
      was approximately 30 copies. We identified affected siblings with repeat
      expansions, of different sizes, on the same haplotype, which confirms the
      repeat's instability during transmissions. Expansions were observed directly;
      contractions were deduced by comparison of allele sizes within a family. In a
      sample of 28 patients, we found no correlation between age at onset of EPM1 and
      the size of the expanded dodecamer. This suggests that once the dodecamer repeat
      expands beyond a critical threshold, cystatin B expression is reduced in certain
      cells, with pathological consequences.

PMID- 9529357
TI  - A locus for autosomal recessive hypodontia with associated dental anomalies maps
      to chromosome 16q12.1.

PMID- 9529358
TI  - Quantitative analysis of fetal DNA in maternal plasma and serum: implications for
      noninvasive prenatal diagnosis.
AB  - We have developed a real-time quantitative PCR assay to measure the concentration
      of fetal DNA in maternal plasma and serum. Our results show that fetal DNA is
      present in high concentrations in maternal plasma, reaching a mean of 25.4 genome
      equivalents/ml (range 3.3-69. 4) in early pregnancy and 292.2 genome
      equivalents/ml (range 76. 9-769) in late pregnancy. These concentrations
      correspond to 3.4% (range 0.39%-11.9%) and 6.2% (range 2.33%-11.4%) of the total
      plasma DNA in early and late pregnancy, respectively. Sequential follow-up study
      of women who conceived by in vitro fertilization shows that fetal DNA can be
      detected in maternal serum as early as the 7th wk of gestation and that it then
      increases in concentration as pregnancy progresses. These data suggest that fetal
      DNA can be readily detected in maternal plasma and serum and may be a valuable
      source of material for noninvasive prenatal diagnosis.

PMID- 9529360
TI  - A log-linear approach to case-parent-triad data: assessing effects of disease
      genes that act either directly or through maternal effects and that may be
      subject to parental imprinting.
AB  - We describe a log-linear method for analysis of case-parent-triad data, based on
      maximum likelihood with stratification on parental mating type. The method leads
      to estimates of association parameters, such as relative risks, for a single
      allele, and also to likelihood ratio chi2 tests (LRTs) of linkage disequilibrium.
      Hardy-Weinberg equilibrium need not be assumed. Our simulations suggest that the
      LRT has power similar to that of the chi2 "score" test proposed by Schaid and
      Sommer and that both can outperform the transmission/disequilibrium test (TDT),
      although the TDT can perform better under an additive model of inheritance.
      Because a restricted version of the LRT is asymptotically equivalent to the TDT,
      the proposed test can be regarded as a generalization of the TDT. The method that
      we describe generalizes easily to accommodate maternal effects on risk and, in
      fact, produces powerful and orthogonal tests of the contribution of fetal versus
      maternal genetic factors. We further generalize the model to allow for effects of
      parental imprinting. Imprinting effects can be fitted by a simple, iterative
      procedure that relies on the expectation-maximization algorithm and that uses
      standard statistical software for the maximization steps. Simulations reveal that
      LRT tests for detection of imprinting have very good operating characteristics.
      When a single allele is under study, the proposed method can yield powerful tests
      for detection of linkage disequilibrium and is applicable to a broader array of
      causal scenarios than is the TDT.

PMID- 9529361
TI  - A clinical variant of neurofibromatosis type 1: familial spinal neurofibromatosis
      with a frameshift mutation in the NF1 gene.
AB  - Spinal neurofibromatosis (SNF) has been considered to be an alternative form of
      neurofibromatosis in which spinal cord tumors are the main clinical
      characteristic. Familial SNF has been reported, elsewhere, in three families-two
      linked to markers within the gene for neurofibromatosis type 1 (NF1) and the
      other not linked to NF1-but no molecular alterations have been described in these
      families. We describe a three-generation family that includes five members
      affected by SNF. All the affected members presented multiple spinal neurofibromas
      and cafe au lait spots, one member had cutaneous neurofibromas, and some members
      had other signs of NF1. Genetic analysis, performed with markers within and
      flanking the NF1 gene, showed segregation with the NF1 locus. Mutation analysis,
      performed with the protein-truncation test and SSCP/heteroduplex analysis of the
      whole coding region of the NF1 gene, identified a frameshift mutation (8042insA)
      in exon 46, which should result in a truncated NF1 protein. The 8042insA mutation
      was detected in all five family members with the SNF/NF1 phenotype. To our
      knowledge, this is the first time that a mutation in the NF1 gene has been
      associated with SNF. The clinical homogeneity in the severity of the disease
      among the affected members of the family, which is unusual in NF1, suggests that
      a particular property of the NF1 mutation described here, a gene closely linked
      to NF1, or posttranscriptional events are involved in this severe neurological
      phenotype.

PMID- 9529362
TI  - Evidence that lymphangiomyomatosis is caused by TSC2 mutations: chromosome 16p13
      loss of heterozygosity in angiomyolipomas and lymph nodes from women with
      lymphangiomyomatosis.
AB  - Lymphangiomyomatosis (LAM) is a rare disease, of unknown etiology, affecting
      women almost exclusively. Lung transplantation is the only consistently effective
      therapy for LAM. Microscopically, LAM consists of a diffuse proliferation of
      smooth muscle cells. LAM can occur without evidence of other disease (referred to
      as "sporadic LAM") or in association with tuberous sclerosis complex (TSC). TSC
      is an autosomal dominant tumor suppressor gene syndrome characterized by
      seizures, mental retardation, and tumors in the brain, heart, skin, and kidney.
      Renal angiomyolipomas occur in approximately 50% of sporadic LAM patients and in
      70% of TSC patients. Loss of heterozygosity (LOH) in the chromosomal region for
      the TSC2 gene occurs in 60% of TSC-associated angiomyolipomas. Because of the
      similar pulmonary and renal manifestations of TSC and sporadic LAM, we
      hypothesized that LAM and TSC have a common genetic basis. We analyzed renal
      angiomyolipomas, from 13 women with sporadic LAM, for LOH in the regions of the
      TSC1 (chromosome 9q34) and TSC2 (chromosome 16p13) genes. TSC2 LOH was detected
      in seven (54%) of the angiomyolipomas. We also found TSC2 LOH in four lymph nodes
      from a woman with retroperitoneal LAM. No TSC1 LOH was found. Our findings
      indicate that the TSC2 gene may be involved in the pathogenesis of sporadic LAM.
      However, genetic transmission of LAM has not been reported. Women with LAM may
      have low-penetrance germ-line TSC2 mutations, or they may be mosaic, with TSC2
      mutations in the lung and the kidney but not in other organs.

PMID- 9529363
TI  - Mutation and polymorphism analysis of the human homogentisate 1, 2-dioxygenase
      gene in alkaptonuria patients.
AB  - Alkaptonuria (AKU), a rare hereditary disorder of phenylalanine and tyrosine
      catabolism, was the first disease to be interpreted as an inborn error of
      metabolism. AKU patients are deficient for homogentisate 1,2 dioxygenase (HGO);
      this deficiency causes homogentisic aciduria, ochronosis, and arthritis. We
      cloned the human HGO gene and characterized two loss-of-function mutations, P230S
      and V300G, in the HGO gene in AKU patients. Here we report haplotype and
      mutational analysis of the HGO gene in 29 novel AKU chromosomes. We identified 12
      novel mutations: 8 (E42A, W97G, D153G, S189I, I216T, R225H, F227S, and M368V)
      missense mutations that result in amino acid substitutions at positions conserved
      in HGO in different species, 1 (F10fs) frameshift mutation, 2 intronic mutations
      (IVS9-56G-->A, IVS9-17G-->A), and 1 splice-site mutation (IVS5+1G-->T). We also
      report characterization of five polymorphic sites in HGO and describe the
      haplotypic associations of alleles at these sites in normal and AKU chromosomes.
      One of these sites, HGO-3, is a variable dinucleotide repeat; IVS2+35T/A,
      IVS5+25T/C, and IVS6+46C/A are intronic sites at which single nucleotide
      substitutions (dimorphisms) have been detected; and c407T/A is a relatively
      frequent nucleotide substitution in the coding sequence, exon 4, resulting in an
      amino acid change (H80Q). These data provide insight into the origin and
      evolution of the various AKU alleles.

PMID- 9529364
TI  - Identification of constitutional WT1 mutations, in patients with isolated diffuse
      mesangial sclerosis, and analysis of genotype/phenotype correlations by use of a
      computerized mutation database.
AB  - Constitutional mutations of the WT1 gene, encoding a zinc-finger transcription
      factor involved in renal and gonadal development, are found in most patients with
      Denys-Drash syndrome (DDS), or diffuse mesangial sclerosis (DMS) associated with
      pseudohermaphroditism and/or Wilms tumor (WT). Most mutations in DDS patients lie
      in exon 8 or exon 9, encoding zinc finger 2 or zinc finger 3, respectively, with
      a hot spot (R394W) in exon 9. We analyzed a series of 24 patients, 10 with
      isolated DMS (IDMS), 10 with DDS, and 4 with urogenital abnormalities and/or WT.
      We report WT1 heterozygous mutations in 16 patients, 4 of whom presented with
      IDMS. One male and two female IDMS patients with WT1 mutations underwent normal
      puberty. Two mutations associated with IDMS are different from those described in
      DDS patients. No WT1 mutations were detected in the six other IDMS patients,
      suggesting genetic heterogeneity of this disease. We analyzed genotype/phenotype
      correlations, on the basis of the constitution of a WT1 mutation database of 84
      germ-line mutations, to compare the distribution and type of mutations, according
      to the different symptoms. This demonstrated (1) the association between
      mutations in exons 8 and 9 and DMS; (2) among patients with DMS, a higher
      frequency of exon 8 mutations among 46, XY patients with female phenotype than
      among 46,XY patients with sexual ambiguity or male phenotype; and (3)
      statistically significant evidence that mutations in exons 8 and 9 preferentially
      affect amino acids with different functions.

PMID- 9529367
TI  - Fetal DNA in maternal plasma: the plot thickens and the placental barrier thins.

PMID- 9529365
TI  - Novel mutations in the connexin 26 gene (GJB2) that cause autosomal recessive
      (DFNB1) hearing loss.
AB  - Mutations in the connexin 26 (Cx26) gene (GJB2) are associated with the type of
      autosomal recessive nonsyndromic neurosensory deafness known as "DFNB1." Studies
      indicate that DFNB1 (13q11-12) causes 20% of all childhood deafness and may have
      a carrier rate as high as 2. 8%. This study describes the analysis of 58
      multiplex families each having at least two affected children diagnosed with
      autosomal recessive nonsyndromic deafness. Twenty of the 58 families were
      observed to have mutations in both alleles of Cx26. Thirty-three of 116
      chromosomes contained a 30delG allele, for a frequency of .284. This mutation was
      observed in 2 of 192 control chromosomes, for an estimated gene frequency of
      .01+/-.007. The homozygous frequency of the 30delG allele is then estimated at
      .0001, or 1/10,000. Given that the frequency of all childhood hearing impairment
      is 1/1,000 and that half of that is genetic, the specific mutation 30delG is
      responsible for 10% of all childhood hearing loss and for 20% of all childhood
      hereditary hearing loss. Six novel mutations were also observed in the affected
      population. The deletions detected cause frameshifts that would severely disrupt
      the protein structure. Three novel missense mutations, Val84Met, Val95Met, and
      Ser113Pro, were observed. The missense mutation 101T-->C has been reported to be
      a dominant allele of DFNA3, a dominant nonsyndromic hearing loss. Data further
      supporting the finding that this mutation does not cause dominant hearing loss
      are presented. This allele was found in a recessive family segregating
      independently from the hearing-loss phenotype and in 3 of 192 control
      chromosomes. These results indicate that 101T-->C is not sufficient to cause
      hearing loss.

PMID- 9529368
TI  - Are we ready to try to cure alkaptonuria?

PMID- 9529369
TI  - Mitochondrial genetics '98 is the bottleneck cracked?

PMID- 9529371
TI  - The myoclonic epilepsy and ragged-red fiber mutation provides new insights into
      human mitochondrial function and genetics.

PMID- 9529370
TI  - Mitochondrial dysfunction in idiopathic Parkinson disease.
AB  - Disordered mitochondrial metabolism may play an important role in a number of
      idiopathic neurodegenerative disorders. The question of mitochondrial dysfunction
      is particularly attractive in the case of idiopathic Parkinson disease (PD),
      since Vyas et al. recognized in the 1980s that the parkinsonism-inducing compound
      N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine is a mitochondrial toxin. The unique
      genetic properties of mitochondria also make them worthy of consideration for a
      pathogenic role in PD, as well as in other late-onset, sporadic neurodegenerative
      disorders. Although affected persons occasionally do provide family histories
      that suggest Mendelian inheritance, the vast majority of the time these diseases
      appear sporadically. Because of unique features such as heteroplasmy, replicative
      segregation, and threshold effects, mitochondrial inheritance can allow for the
      apparent sporadic nature of these diseases.

PMID- 9529372
TI  - Down-regulation of platelet endothelial cell adhesion molecule-1 results in
      thrombospondin-1 expression and concerted regulation of endothelial cell
      phenotype.
AB  - bEND.3 cells are polyoma middle T-transformed mouse brain endothelial cells that
      express very little or no thrombospondin-1, a natural inhibitor of angiogenesis,
      but express high levels of platelet endothelial cell adhesion molecule-1 (PECAM
      1) that localizes to sites of cell-cell contact. Here, we have examined the role
      of PECAM-1 in regulation of bEND.3 cell proliferation, migration, morphogenesis,
      and hemangioma formation. We show that down-regulating PECAM-1 expression by
      antisense transfection of bEND. 3 cells has a dramatic effect on their
      morphology, proliferation, and morphogenesis on Matrigel. There is an optimal
      level for PECAM-1 expression such that high levels of PECAM-1 inhibit, whereas
      moderate levels of PECAM-1 stimulate, endothelial cell morphogenesis. The down
      regulation of PECAM-1 in bEND.3 cells resulted in reexpression of endogenous
      thrombospondin-1 and its antiangiogenic receptor CD36. The expression of the
      vascular endothelial growth factor receptors flk-1 and flt-1, as well as
      integrins and metalloproteinases (which are involved in angiogenesis), were also
      affected. These observations are consistent with the changes observed in
      proliferation, migration, and adhesion characteristics of the antisense
      transfected bEND.3 cells as well as with their lack of ability to form
      hemangiomas in mice. Thus, a reciprocal relationship exists between
      thrombospondin-1 and PECAM-1 expression, such that these two molecules appear to
      be constituents of a "switch" that regulates in concert many components of the
      angiogenic and differentiated phenotypes of endothelial cells.

PMID- 9529373
TI  - beta1-integrin cytoplasmic subdomains involved in dominant negative function.
AB  - The beta1-integrin cytoplasmic domain consists of a membrane proximal subdomain
      common to the four known isoforms ("common" region) and a distal subdomain
      specific for each isoform ("variable" region). To investigate in detail the role
      of these subdomains in integrin-dependent cellular functions, we used beta1A and
      beta1B isoforms as well as four mutants lacking the entire cytoplasmic domain
      (beta1TR), the variable region (beta1COM), or the common region (beta1 deltaCOM-B
      and beta1 deltaCOM-A). By expressing these constructs in Chinese hamster ovary
      and beta1 integrin-deficient GD25 cells (Wennerberg et al., J Cell Biol 132, 227
      238, 1996), we show that beta1B, beta1COM, beta1 deltaCOM-B, and beta1 deltaCOM-A
      molecules are unable to support efficient cell adhesion to matrix proteins. On
      exposure to Mn++ ions, however, beta1B, but none of the mutants, can mediate cell
      adhesion, indicating specific functional properties of this isoform. Analysis of
      adhesive functions of transfected cells shows that beta1B interferes in a
      dominant negative manner with beta1A and beta3/beta5 integrins in cell spreading,
      focal adhesion formation, focal adhesion kinase tyrosine phosphorylation, and
      fibronectin matrix assembly. None of the beta1 mutants tested shows this
      property, indicating that the dominant negative effect depends on the specific
      combination of common and B subdomains, rather than from the absence of the A
      subdomain in the beta1B isoform.

PMID- 9529374
TI  - Assembly of lampbrush chromosomes from sperm chromatin.
AB  - We have examined the behavior of demembranated sperm heads when injected into the
      germinal vesicle (GV) of amphibian oocytes. Xenopus sperm heads injected into
      Xenopus GVs swelled immediately and within hours began to stain with an antibody
      against RNA polymerase II (Pol II). Over time each sperm head became a loose mass
      of chromosome-like threads, which by 24-48 h resolved into individually
      recognizable lampbrush chromosomes (LBCs). Although LBCs derived from sperm are
      unreplicated single chromatids, their morphology and immunofluorescent staining
      properties were strikingly similar to those of the endogenous lampbrush
      bivalents. They displayed typical transcriptionally active loops extending from
      an axis of condensed chromomeres, as well as locus-specific "landmarks. "
      Experiments with [3H]GTP and actinomycin D demonstrated that transcription was
      not necessary for the initial swelling of the sperm heads and acquisition of Pol
      II but was required for maintenance of the lampbrush loops. Splicing was not
      required at any stage during formation of sperm LBCs. When Xenopus sperm heads
      were injected into GVs of the newt Notophthalmus, the resulting sperm LBCs
      displayed very long loops with pronounced Pol II axes, like those of the
      endogenous newt LBCs; as expected, they stained with antibodies against newt
      specific proteins. Other heterologous injections, including sperm heads of the
      frog Rana pipiens and the zebrafish Danio rerio in Xenopus GVs, confirm that LBCs
      can be derived from taxonomically distant organisms. The GV system should help
      identify both cis- and trans-acting factors needed to convert condensed chromatin
      into transcriptionally active LBCs. It may also be useful in producing
      cytologically analyzable chromosomes from organisms whose oocytes do not go
      through a typical lampbrush phase or cannot be manipulated by current techniques.

PMID- 9529375
TI  - Epidermal growth factor signaling and mitogenesis in Plcg1 null mouse embryonic
      fibroblasts.
AB  - Gene targeting techniques and early mouse embryos have been used to produce
      immortalized fibroblasts genetically deficient in phospholipase C (PLC)-gamma1, a
      ubiquitous tyrosine kinase substrate. Plcg1(-/-) embryos die at embryonic day 9;
      however, cells derived from these embryos proliferate as well as cells from
      Plcg1(+/+) embryos. The null cells do grow to a higher saturation density in
      serum-containing media, as their capacity to spread out is decreased compared
      with that of wild-type cells. In terms of epidermal growth factor receptor
      activation and internalization, or growth factor induction of mitogen-activated
      protein kinase, c-fos, or DNA synthesis in quiescent cells, PLcg1(-/-) cells
      respond equivalently to PLcg1(+/+) cells. Also, null cells are able to migrate
      effectively in a wounded monolayer. Therefore, immortalized fibroblasts do not
      require PLC-gamma1 for many responses to growth factors.

PMID- 9529376
TI  - New alleles of the yeast MPS1 gene reveal multiple requirements in spindle pole
      body duplication.
AB  - In Saccharomyces cerevisiae, the Mps1p protein kinase is critical for both
      spindle pole body (SPB) duplication and the mitotic spindle assembly checkpoint.
      The mps1-1 mutation causes failure early in SPB duplication, and because the
      spindle assembly checkpoint is also compromised, mps1-1 cells proceed with a
      monopolar mitosis and rapidly lose viability. Here we report the genetic and
      molecular characterization of mps1-1 and five new temperature-sensitive alleles
      of MPS1. Each of the six alleles contains a single point mutation in the region
      of the gene encoding the protein kinase domain. The mutations affect several
      residues conserved among protein kinases, most notably the invariant glutamate in
      subdomain III. In vivo and in vitro kinase activity of the six epitope-tagged
      mutant proteins varies widely. Only two display appreciable in vitro activity,
      and interestingly, this activity is not thermolabile under the assay conditions
      used. While five of the six alleles cause SPB duplication to fail early, yielding
      cells with a single SPB, mps1-737 cells proceed into SPB duplication and assemble
      a second SPB that is structurally defective. This phenotype, together with the
      observation of intragenic complementation between this unique allele and two
      others, suggests that Mps1p is required for multiple events in SPB duplication.

PMID- 9529377
TI  - Spc98p directs the yeast gamma-tubulin complex into the nucleus and is subject to
      cell cycle-dependent phosphorylation on the nuclear side of the spindle pole
      body.
AB  - In the yeast Saccharomyces cerevisiae, microtubules are organized by the spindle
      pole body (SPB), which is embedded in the nuclear envelope. Microtubule
      organization requires the gamma-tubulin complex containing the gamma-tubulin
      Tub4p, Spc98p, and Spc97p. The Tub4p complex is associated with cytoplasmic and
      nuclear substructures of the SPB, which organize the cytoplasmic and nuclear
      microtubules. Here we present evidence that the Tub4p complex assembles in the
      cytoplasm and then either binds to the cytoplasmic side of the SPB or is imported
      into the nucleus followed by binding to the nuclear side of the SPB. Nuclear
      import of the Tub4p complex is mediated by the essential nuclear localization
      sequence of Spc98p. Our studies also indicate that Spc98p in the Tub4p complex is
      phosphorylated at the nuclear, but not at the cytoplasmic, side of the SPB. This
      phosphorylation is cell cycle dependent and occurs after SPB duplication and
      nucleation of microtubules by the new SPB and therefore may have a role in
      mitotic spindle function. In addition, activation of the mitotic checkpoint
      stimulates Spc98p phosphorylation. The kinase Mps1p, which functions in SPB
      duplication and mitotic checkpoint control, seems to be involved in Spc98p
      phosphorylation. Our results also suggest that the nuclear and cytoplasmic Tub4p
      complexes are regulated differently.

PMID- 9529379
TI  - The kinetics of mannose 6-phosphate receptor trafficking in the endocytic pathway
      in HEp-2 cells: the receptor enters and rapidly leaves multivesicular endosomes
      without accumulating in a prelysosomal compartment.
AB  - We have previously shown that in HEp-2 cells, multivesicular bodies (MVBs)
      processing internalized epidermal growth factor-epidermal growth factor receptor
      complexes mature and fuse directly with lysosomes in which the complexes are
      degraded. The MVBs do not fuse with a prelysosomal compartment enriched in
      mannose 6-phosphate receptor (M6PR) as has been described in other cell types.
      Here we show that the cation-independent M6PR does not become enriched in the
      endocytic pathway en route to the lysosome, but if a pulse of M6PR or an M6PR
      ligand, cathepsin D, is followed, a significant fraction of these proteins are
      routed from the trans-Golgi to MVBs. Accumulation of M6PR does not occur because
      when the ligand dissociates, the receptor rapidly leaves the MVB. At steady
      state, most M6PR are distributed within the trans-Golgi and trans-Golgi network
      and in vacuolar structures distributed in the peripheral cytoplasm. We suggest
      that these M6PR-rich vacuoles are on the return route from MVBs to the trans
      Golgi network and that a separate stable M6PR-rich compartment equivalent to the
      late endosome/prelysosome stage does not exist on the endosome-lysosome pathway
      in these cells.

PMID- 9529378
TI  - Reprogramming the cell cycle for endoreduplication in rodent trophoblast cells.
AB  - Differentiation of trophoblast giant cells in the rodent placenta is accompanied
      by exit from the mitotic cell cycle and onset of endoreduplication. Commitment to
      giant cell differentiation is under developmental control, involving down
      regulation of Id1 and Id2, concomitant with up-regulation of the basic helix-loop
      helix factor Hxt and acquisition of increased adhesiveness. Endoreduplication
      disrupts the alternation of DNA synthesis and mitosis that maintains euploid DNA
      content during proliferation. To determine how the mammalian endocycle is
      regulated, we examined the expression of the cyclins and cyclin-dependent kinases
      during the transition from replication to endoreduplication in the Rcho-1 rat
      choriocarcinoma cell line. We cultured these cells under conditions that gave
      relatively synchronous endoreduplication. This allowed us to study the events
      that occur during the transition from the mitotic cycle to the first endocycle.
      With giant cell differentiation, the cells switched cyclin D isoform expression
      from D3 to D1 and altered several checkpoint functions, acquiring a relative
      insensitivity to DNA-damaging agents and a coincident serum independence. The
      initiation of S phase during endocycles appeared to involve cycles of synthesis
      of cyclins E and A, and termination of S was associated with abrupt loss of
      cyclin A and E. Both cyclins were absent from gap phase cells, suggesting that
      their degradation may be necessary to allow reinitiation of the endocycle. The
      arrest of the mitotic cycle at the onset of endoreduplication was associated with
      a failure to assemble cyclin B/p34(cdk1) complexes during the first endocycle. In
      subsequent endocycles, cyclin B expression was suppressed. Together these data
      suggest several points at which cell cycle regulation could be targeted to shift
      cells from a mitotic to an endoreduplicative cycle.

PMID- 9529380
TI  - Folding of active beta-lactamase in the yeast cytoplasm before translocation into
      the endoplasmic reticulum.
AB  - Polypeptides targeted to the yeast endoplasmic reticulum (ER) posttranslationally
      are thought to be kept in the cytoplasm in an unfolded state by Hsp70 chaperones
      before translocation. We show here that Escherichia coli beta-lactamase
      associated with Hsp70, but adopted a native-like conformation before
      translocation in living Saccharomyces cerevisiae cells. beta-Lactamase is a
      globular trypsin-resistant molecule in authentic form. For these studies, it was
      linked to the C terminus of a yeast polypeptide Hsp150delta, which conferred
      posttranslational translocation and provided sites for O-glycosylation. We
      devised conditions to retard translocation of Hsp150delta-beta-lactamase. This
      enabled us to show by protease protection assays that an unglycosylated precursor
      was associated with the cytoplasmic surface of isolated microsomes, whereas a
      glycosylated form resided inside the vesicles. Both proteins were trypsin
      resistant and had similar beta-lactamase activity and Km values for nitrocefin.
      The enzymatically active cytoplasmic intermediate could be chased into the ER,
      followed by secretion of the activity to the medium. Productive folding in the
      cytoplasm occurred in the absence of disulfide formation, whereas in the ER
      lumen, proper folding required oxidation of the sulfhydryls. This suggests that
      the polypeptide was refolded in the ER and consequently, at least partially
      unfolded for translocation.

PMID- 9529381
TI  - Mapping of a myosin-binding domain and a regulatory phosphorylation site in M
      protein, a structural protein of the sarcomeric M band.
AB  - The myofibrils of cross-striated muscle fibers contain in their M bands
      cytoskeletal proteins whose main function seems to be the stabilization of the
      three-dimensional arrangement of thick filaments. We identified two immunoglobin
      domains (Mp2-Mp3) of M-protein as a site binding to the central region of light
      meromyosin. This binding is regulated in vitro by phosphorylation of a single
      serine residue (Ser76) in the immediately adjacent amino-terminal domain Mp1. M
      protein phosphorylation by cAMP-dependent kinase A inhibits binding to myosin
      LMM. Transient transfection studies of cultured cells revealed that the myosin
      binding site seems involved in the targeting of M-protein to its location in the
      myofibril. Using the same method, a second myofibril-binding site was uncovered
      in domains Mp9-Mp13. These results support the view that specific phosphorylation
      events could be also important for the control of sarcomeric M band formation and
      remodeling.

PMID- 9529382
TI  - Arp2/3 complex from Acanthamoeba binds profilin and cross-links actin filaments.
AB  - The Arp2/3 complex was first purified from Acanthamoeba castellanii by profilin
      affinity chromatography. The mechanism of interaction with profilin was unknown
      but was hypothesized to be mediated by either Arp2 or Arp3. Here we show that the
      Arp2 subunit of the complex can be chemically cross-linked to the actin-binding
      site of profilin. By analytical ultracentrifugation, rhodamine-labeled profilin
      binds Arp2/3 complex with a Kd of 7 microM, an affinity intermediate between the
      low affinity of profilin for barbed ends of actin filaments and its high affinity
      for actin monomers. These data suggest the barbed end of Arp2 is exposed, but
      Arp2 and Arp3 are not packed together in the complex exactly like two actin
      monomers in a filament. Arp2/3 complex also cross-links actin filaments into
      small bundles and isotropic networks, which are mechanically stiffer than
      solutions of actin filaments alone. Arp2/3 complex is concentrated at the leading
      edge of motile Acanthamoeba, and its localization is distinct from that of alpha
      actinin, another filament cross-linking protein. Based on localization and actin
      filament nucleation and cross-linking activities, we propose a role for Arp2/3 in
      determining the structure of the actin filament network at the leading edge of
      motile cells.

PMID- 9529383
TI  - Dissection of de novo membrane insertion activities of internal transmembrane
      segments of ATP-binding-cassette transporters: toward understanding topological
      rules for membrane assembly of polytopic membrane proteins.
AB  - The membrane assembly of polytopic membrane proteins is a complicated process.
      Using Chinese hamster P-glycoprotein (Pgp) as a model protein, we investigated
      this process previously and found that Pgp expresses more than one topology. One
      of the variations occurs at the transmembrane (TM) domain including TM3 and TM4:
      TM4 inserts into membranes in an N(in)-C(out) rather than the predicted N(out)
      C(in) orientation, and TM3 is in cytoplasm rather than the predicted N(in)-C(out)
      orientation in the membrane. It is possible that TM4 has a strong activity to
      initiate the N(in)-C(out) membrane insertion, leaving TM3 out of the membrane.
      Here, we tested this hypothesis by expressing TM3 and TM4 in isolated conditions.
      Our results show that TM3 of Pgp does not have de novo N(in)-C(out) membrane
      insertion activity whereas TM4 initiates the N(in)-C(out) membrane insertion
      regardless of the presence of TM3. In contrast, TM3 and TM4 of another polytopic
      membrane protein, cystic fibrosis transmembrane conductance regulator (CFTR),
      have a similar level of de novo Nin-Cout membrane insertion activity and TM4 of
      CFTR functions only as a stop-transfer sequence in the presence of TM3. Based on
      these findings, we propose that 1) the membrane insertion of TM3 and TM4 of Pgp
      does not follow the sequential model, which predicts that TM3 initiates N(in)
      C(out) membrane insertion whereas TM4 stops the insertion event; and 2) "leaving
      one TM segment out of the membrane" may be an important folding mechanism for
      polytopic membrane proteins, and it is regulated by the N(in)-C(out) membrane
      insertion activities of the TM segments.

PMID- 9529384
TI  - The thrombospondin receptor CD47 (IAP) modulates and associates with alpha2 beta1
      integrin in vascular smooth muscle cells.
AB  - The carboxyl-terminal domain of thrombospondin-1 enhances the migration and
      proliferation of smooth muscle cells. Integrin-associated protein (IAP or CD47)
      is a receptor for the thrombospondin-1 carboxyl-terminal cell-binding domain and
      binds the agonist peptide 4N1K (kRFYVVMWKk) from this domain. 4N1K peptide
      stimulates chemotaxis of both human and rat aortic smooth muscle cells on gelatin
      coated filters. The migration on gelatin is specifically blocked by monoclonal
      antibodies against IAP and a beta1 integrin, rather than alphav beta3 as found
      previously for 4N1K-stimulated chemotaxis of endothelial cells on gelatin. Both
      human and rat smooth muscle cells displayed a weak migratory response to soluble
      type I collagen; however, the presence of 4N1K peptide or intact thrombospondin-1
      provoked a synergistic chemotactic response that was partially blocked by
      antibodies to alpha2 and beta1 integrin subunits and to IAP. A combination of
      antialpha2 and IAP monoclonal antibodies completely blocked chemotaxis. RGD
      peptide and antialphav beta3 mAb were without effect. 4N1K and thrombospondin-1
      did not augment the chemotactic response of smooth muscle cells to fibronectin,
      vitronectin, or collagenase-digested type I collagen. Complex formation between
      alpha2 beta1 and IAP was detected by the coimmunoprecipitation of both alpha2 and
      beta1 integrin subunits with IAP. These data suggest that IAP can associate with
      alpha2 beta1 integrin and modulate its function.

PMID- 9529385
TI  - Synthesis, storage, and release of vascular endothelial growth factor/vascular
      permeability factor (VEGF/VPF) by human mast cells: implications for the
      biological significance of VEGF206.
AB  - Mast cells have been implicated in various diseases that are accompanied by
      neovascularization. The exact mechanisms by which mast cells might mediate an
      angiogenic response, however, are unclear and therefore, we have investigated the
      possible expression of vascular endothelial growth factor/vascular permeability
      factor (VEGF/VPF) in the human mast cell line HMC-1 and in human skin mast cells.
      Reverse transcription-polymerase chain reaction (RT-PCR) analysis revealed that
      mast cells constitutively express VEGF121, VEGF165, and VEGF189. After a
      prolonged stimulation of cells for 24 h with phorbol 12-myristate 13-acetate
      (PMA) and the ionophore A23187, an additional transcript representing VEGF206 was
      detectable, as could be verified by sequence analysis. These results were
      confirmed at the protein level by Western blot analysis. When the amounts of VEGF
      released under unstimulated and stimulated conditions were compared, a
      significant increase was detectable after stimulation of cells. Human
      microvascular endothelial cells (HMVEC) responded to the supernatant of
      unstimulated HMC-1 cells with a dose-dependent mitogenic effect, neutralizable up
      to 90% in the presence of a VEGF-specific monoclonal antibody. Flow cytometry and
      postembedding immunoelectron microscopy were used to detect VEGF in its cell
      associated form. VEGF was exclusively detectable in the secretory granules of
      isolated human skin mast cells. These results show that both normal and leukemic
      human mast cells constitutively express bioactive VEGF. Furthermore, this study
      contributes to the understanding of the physiological role of the strongly
      heparin-binding VEGF isoforms, since these were found for the first time to be
      expressed in an activation-dependent manner in HMC-1 cells.

PMID- 9529386
TI  - Mechanisms governing the activation and trafficking of yeast G protein-coupled
      receptors.
AB  - We have addressed the mechanisms governing the activation and trafficking of G
      protein-coupled receptors (GPCRs) by analyzing constitutively active mating
      pheromone receptors (Ste2p and Ste3p) of the yeast Saccharomyces cerevisiae.
      Substitution of the highly conserved proline residue in transmembrane segment VI
      of these receptors causes constitutive signaling. This proline residue may
      facilitate folding of GPCRs into native, inactive conformations, and/or mediate
      agonist-induced structural changes leading to G protein activation. Constitutive
      signaling by mutant receptors is suppressed upon coexpression with wild-type, but
      not G protein coupling-defective, receptors. Wild-type receptors may therefore
      sequester a limiting pool of G proteins; this apparent "precoupling" of receptors
      and G proteins could facilitate signal production at sites where cell surface
      projections form during mating partner discrimination. Finally, rather than being
      expressed mainly at the cell surface, constitutively active pheromone receptors
      accumulate in post-endoplasmic reticulum compartments. This is in contrast to
      other defective membrane proteins, which apparently are targeted by default to
      the vacuole. We suggest that the quality-control mechanism that retains receptors
      in post-endoplasmic reticulum compartments may normally allow wild-type receptors
      to fold into their native, fully inactive conformations before reaching the cell
      surface. This may ensure that receptors do not trigger a response in the absence
      of agonist.

PMID- 9529387
TI  - Dimerization of the polymeric immunoglobulin receptor controls its transcytotic
      trafficking.
AB  - Binding of dimeric immunoglobulin (Ig)A to the polymeric Ig receptor (pIgR)
      stimulates transcytosis of pIgR across epithelial cells. Through the generation
      of a series of pIgR chimeric constructs, we have tested the ability of ligand to
      promote receptor dimerization and the subsequent role of receptor dimerization on
      its intracellular trafficking. Using the cytoplasmic domain of the T cell
      receptor-zeta chain as a sensitive indicator of receptor oligomerization, we show
      that a pIgR:zeta chimeric receptor expressed in Jurkat cells initiates a zeta
      specific signal transduction cascade when exposed to dimeric or tetrameric IgA,
      but not when exposed to monomeric IgA. In addition, we replaced the pIgR's
      transmembrane domain with that of glycophorin A to force dimerization or with a
      mutant glycophorin transmembrane domain to prevent dimerization. Forcing
      dimerization stimulated transcytosis of the chimera, whereas preventing
      dimerization abolished ligand-stimulated transcytosis. We conclude that binding
      of dimeric IgA to the pIgR induces its dimerization and that this dimerization is
      necessary and sufficient to stimulate pIgR transcytosis.

PMID- 9529388
TI  - Mitochondrial inheritance is delayed in Saccharomyces cerevisiae cells lacking
      the serine/threonine phosphatase PTC1.
AB  - In wild-type yeast mitochondrial inheritance occurs early in the cell cycle
      concomitant with bud emergence. Cells lacking the PTC1 gene initially produce
      buds without a mitochondrial compartment; however, these buds later receive part
      of the mitochondrial network from the mother cell. Thus, the loss of PTC1 causes
      a delay, but not a complete block, in mitochondrial transport. PTC1 encodes a
      serine/threonine phosphatase in the high-osmolarity glycerol response (HOG)
      pathway. The mitochondrial inheritance delay in the ptc1 mutant is not
      attributable to changes in intracellular glycerol concentrations or defects in
      the organization of the actin cytoskeleton. Moreover, epistasis experiments with
      ptc1delta and mutations in HOG pathway kinases reveal that PTC1 is not acting
      through the HOG pathway to control the timing of mitochondrial inheritance.
      Instead, PTC1 may be acting either directly or through a different signaling
      pathway to affect the mitochondrial transport machinery in the cell. These
      studies indicate that the timing of mitochondrial transport in wild-type cells is
      genetically controlled and provide new evidence that mitochondrial inheritance
      does not depend on a physical link between the mitochondrial network and the
      incipient bud site.

PMID- 9529389
TI  - Homology-dependent gene silencing in Paramecium.
AB  - Microinjection at high copy number of plasmids containing only the coding region
      of a gene into the Paramecium somatic macronucleus led to a marked reduction in
      the expression of the corresponding endogenous gene(s). The silencing effect,
      which is stably maintained throughout vegetative growth, has been observed for
      all Paramecium genes examined so far: a single-copy gene (ND7), as well as
      members of multigene families (centrin genes and trichocyst matrix protein genes)
      in which all closely related paralogous genes appeared to be affected. This
      phenomenon may be related to posttranscriptional gene silencing in transgenic
      plants and quelling in Neurospora and allows the efficient creation of specific
      mutant phenotypes thus providing a potentially powerful tool to study gene
      function in Paramecium. For the two multigene families that encode proteins that
      coassemble to build up complex subcellular structures the analysis presented
      herein provides the first experimental evidence that the members of these gene
      families are not functionally redundant.

PMID- 9529390
TI  - Swi5 controls a novel wave of cyclin synthesis in late mitosis.
AB  - We have shown previously that the Swi5 transcription factor regulates the
      expression of the SIC1 Cdk inhibitor in late mitosis. This suggests that Swi5
      might control other genes with roles in ending mitosis. We identified a gene with
      a Swi5-binding site in the promoter that encoded a protein with high homology to
      Pcl2, a cyclin-like protein that associates with the Cdk Pho85. This gene, PCL9,
      is indeed regulated by Swi5 in late M phase, the only cyclin known to be
      expressed at this point in the cell cycle. The Pcl9 protein is associated with a
      Pho85-dependent protein kinase activity, and the protein is unstable with peak
      levels occurring in late M phase. PCL2 is already known to be expressed in late
      G1 and we find that, in addition, it is also regulated by Swi5 in telophase. The
      expression of PCL2 and PCL9 at this stage of the cell cycle implies a role for
      the Pho85 Cdk at the end of mitosis. Consistent with this a synthetic interaction
      was observed between pho85delta and strains deleted for SIC1, SWI5, and SPO12.
      These and other studies support the notion that the M/G1 switch is a major cell
      cycle transition.

PMID- 9529391
TI  - Fluid-phase markers in the basolateral endocytic pathway accumulate in response
      to the actin assembly-promoting drug Jasplakinolide.
AB  - To investigate the role of filamentous actin in the endocytic pathway, we used
      the cell-permeant drug Jasplakinolide (JAS) to polymerize actin in intact
      polarized Madin-Darby canine kidney (MDCK) cells. The uptake and accumulation of
      the fluid-phase markers fluorescein isothiocyanate (FITC)-dextran and horseradish
      peroxidase (HRP) were followed in JAS-treated or untreated cells with confocal
      fluorescence microscopy, biochemical assays, and electron microscopy.
      Pretreatment with JAS increased the uptake and accumulation of fluid-phase
      markers in MDCK cells. JAS increased endocytosis in a polarized manner, with a
      marked effect on fluid-phase uptake from the basolateral surface but not from the
      apical surface of polarized MDCK cells. The early uptake of FITC-dextran and HRP
      was increased more than twofold in JAS-treated cells. At later times, FITC
      dextran and HRP accumulated in clustered endosomes in the basal and middle
      regions of JAS-treated cells. The large accumulated endosomes were similar to
      late endosomes but they were not colabeled for other late endosome markers, such
      as rab7 or mannose-6-phosphate receptor. JAS altered transport in the endocytic
      pathway at a later stage than the microtubule-dependent step affected by
      nocodazole. JAS also had a notable effect on cell morphology, inducing membrane
      bunching at the apical pole of MDCK cells. Although other studies have implicated
      actin in endocytosis at the apical cell surface, our results provide novel
      evidence that filamentous actin is also involved in the endocytosis of fluid
      phase markers from the basolateral membrane of polarized cells.

PMID- 9529392
TI  - MMR vaccination and autism 1998.

PMID- 9529393
TI  - Hydroxychloroquine retinopathy: is screening necessary?

PMID- 9529394
TI  - Blood transfusion risk: protecting against the unknown.

PMID- 9529395
TI  - Patient data, confidentiality, and electronics.

PMID- 9529396
TI  - Immunosuppressive drugs after lung transplantation.

PMID- 9529397
TI  - Continuing medical education: where next?

PMID- 9529398
TI  - Poverty in rural areas.

PMID- 9529399
TI  - Unpalatable results force cleft surgeons to rethink.

PMID- 9529400
TI  - Acne drug is linked to severe depression.

PMID- 9529401
TI  - Cholesterol screening is not worth while.

PMID- 9529402
TI  - Israel's patent law criticised.

PMID- 9529403
TI  - Two arrested in US for selling organs for transplantation.

PMID- 9529404
TI  - UK blood products are banned.

PMID- 9529405
TI  - Police surgeon service needs modernising.

PMID- 9529406
TI  - Bans on smoking in public become more commonplace.

PMID- 9529407
TI  - Ultrasound treatment for treating the carpal tunnel syndrome: randomised "sham"
      controlled trial.
AB  - OBJECTIVE: To assess the efficacy of ultrasound treatment for mild to moderate
      idiopathic carpal tunnel syndrome. DESIGN: Randomised, double blind, "sham"
      controlled trial with assessments at baseline, after 2 weeks' and 7 weeks'
      treatment, and at a follow up assessment 6 months later (8 months after baseline
      evaluation). SETTING: Outpatient clinic of a university department of physical
      medicine and rehabilitation in Vienna. SUBJECTS: 45 patients with mild to
      moderate bilateral carpal tunnel syndrome as verified by electroneurography.
      INTERVENTION: 20 sessions of ultrasound (active) treatment (1 MHz, 1.0 W/cm2,
      pulsed mode 1:4, 15 minutes per session) applied to the area over the carpal
      tunnel of one wrist, and indistinguishable sham ultrasound treatment applied to
      the other. The first 10 treatments were performed daily (5 sessions/week); 10
      further treatments were twice weekly for 5 weeks. MAIN OUTCOME MEASURES: Score of
      subjective symptom ratings assessed by visual analogue scale; electroneurographic
      measures (for example, motor distal latency and sensory antidromic nerve
      conduction velocity). RESULTS: Improvement was significantly more pronounced in
      actively treated than in sham treated wrists for both subjective symptoms (P <
      0.001, paired t test) and electroneurographic variables (motor distal latency P <
      0.001, paired t test; sensory antidromic nerve conduction velocity P < 0.001,
      paired t test). Effects were sustained at 6 months' follow up. CONCLUSION:
      Results suggest there are satisfying short to medium term effects due to
      ultrasound treatment in patients with mild to moderate idiopathic carpal tunnel
      syndrome. Findings need to be confirmed, and ultrasound treatment will have to be
      compared with standard conservative and invasive treatment options.

PMID- 9529408
TI  - Variations in population health status: results from a United Kingdom national
      questionnaire survey.
AB  - OBJECTIVE: To measure the health of a representative sample of the population of
      the United Kingdom by using the EuroQoL EQ-5D questionnaire. DESIGN: Stratified
      random sample representative of the general population aged 18 and over and
      living in the community. SETTING: United Kingdom. SUBJECTS: 3395 people resident
      in the United Kingdom. MAIN OUTCOME MEASURES: Average values for mobility, self
      care, usual activities, pain or discomfort, and anxiety or depression. RESULTS:
      One in three respondents reported problems with pain or discomfort. There were
      differences in the perception of health according to the respondent's age, social
      class, education, housing tenure, economic position, and smoking behaviour.
      CONCLUSIONS: The EQ-5D questionnaire is a practical way of measuring the health
      of a population and of detecting differences in subgroups of the population.

PMID- 9529409
TI  - Use of calcium channel blockers and risk of suicide: ecological findings
      confirmed in population based cohort study.
AB  - OBJECTIVE: To investigate possible associations between use of cardiovascular
      drugs and suicide. DESIGN: Cross sectional ecological study based on rates of use
      of eight cardiovascular drug groups by outpatients. A population based cohort
      study including users of drugs to control hypertension. SUBJECTS: The ecological
      study included 152 of Sweden's 284 municipalities. The cohort study included all
      inhabitants of one Swedish municipality who during 1988 or 1989 had purchased
      cardiovascular agents from pharmacies within the municipality. Six hundred and
      seventeen subjects (18.2%) were classified as users of calcium channel blockers
      and 2780 (81.8%) as non-users. MAIN OUTCOME MEASURES: Partial correlations (least
      squares method) between rates of use of cardiovascular drugs and age standardised
      mortality from suicide in Swedish municipalities. Hazard ratios for risk of
      suicide with adjustments for difference in age and sex in users of calcium
      channel blockers compared with users of other hypertensive drugs. RESULTS: Among
      the Swedish municipalities the use of each cardiovascular drug group except
      angiotensin converting enzyme inhibitors correlated significantly and positively
      with suicide rates. After adjustment for the use of other cardiovascular drug
      groups, as a substitute for the prevalence of cardiovascular morbidity, only the
      correlation with calcium channel blockers remained significant (r = 0.29, P <
      0.001). In the cohort study, five users and four non-users of calcium channel
      blockers committed suicide during the follow up until the end of 1994. The
      absolute risk associated with use of calcium channel blockers was 1.1 suicides
      per 1000 person years. The relative risk, adjusted for differences in age and
      sex, among users versus non-users was 5.4 (95% confidence interval 1.4 to 20.5).
      CONCLUSIONS: Use of calcium channel blockers may increase the risk of suicide.

PMID- 9529410
TI  - QT and QTc dispersion are accurate predictors of cardiac death in newly diagnosed
      non-insulin dependent diabetes: cohort study.

PMID- 9529411
TI  - How often does surgery for peptic ulceration eradicate Helicobacter pylori?
      Systematic review of 36 studies.

PMID- 9529412
TI  - Controversies in primary care. Setting prescribing budgets in general practice.
      Capitation based prescribing budgets will not work.

PMID- 9529413
TI  - Controversies in primary care. Setting prescribing budgets in general practice.
      Effective prescribing at practice level should be identified and rewarded.

PMID- 9529414
TI  - Science, medicine, and the future. New techniques in laser therapy.

PMID- 9529415
TI  - ABC of allergies. Pathogenic mechanisms: a rational basis for treatment.

PMID- 9529416
TI  - New drug treatment for Alzheimer's disease: lessons for healthcare policy.

PMID- 9529417
TI  - Should measles be eradicated?

PMID- 9529418
TI  - The new genetics. Implications for clinical services in Britain and the United
      States.

PMID- 9529419
TI  - Interprofessional working and continuing medical education.

PMID- 9529420
TI  - Three quarters of delegates drove to conference on impact of environment on
      health.

PMID- 9529421
TI  - Audit of child protection procedures in an A&E department. Notes of all previous
      attendances in Sheffield can be checked.

PMID- 9529422
TI  - Audit of child protection procedures in an A&E department. General practitioners
      need training in child protection.

PMID- 9529423
TI  - Audit of child protection procedures in an A&E department. Checks on children in
      Southend have to be via a social worker.

PMID- 9529424
TI  - Testing of PRODIGY continues.

PMID- 9529425
TI  - Survey of French prison found that injecting drug use and tattooing occurred.

PMID- 9529426
TI  - Children with enuresis. Nowadays, a strong suspicion of sexual abuse would prompt
      full investigation.

PMID- 9529427
TI  - Children with enuresis. Most cases of primary nocturnal enuresis are caused by
      isolated developmental immaturity.

PMID- 9529428
TI  - Is histological examination of tissue removed by GPs always necessary? Even
      specialists get the clinical diagnosis wrong.

PMID- 9529429
TI  - Is histological examination of tissue removed by GP's always necessary.
      Clinically important skin lesions would have been missed with a selective
      histological approach.

PMID- 9529430
TI  - Is histological examination of tissue removed by GP's always necessary. Over 10
      days two important lesions were sent to histopathologists in Sheffield.

PMID- 9529431
TI  - Is histological examination of tissue removed by GP's always necessary. More skin
      carcinomas might be detected with routine histological examination.

PMID- 9529432
TI  - Responsibility for decision to give transfusion remains with doctor, not patient.

PMID- 9529433
TI  - Incidence of epilepsy is now higher in elderly people than children.

PMID- 9529434
TI  - Community institutional care for frail elderly people. "Unitary care" homes might
      be the answer.

PMID- 9529435
TI  - Community institutional care for frail elderly people. A multidisciplinary,
      multiagency approach should be the rule.

PMID- 9529436
TI  - Article about Mental Health Act was misleading.

PMID- 9529437
TI  - Self help groups and professionally conducted group interventions are different.

PMID- 9529438
TI  - Septic and aseptic post-operative discitis in the lumbar spine--evaluation by MR
      imaging.
AB  - PURPOSE: The aim of this study was to determine whether it was possible to
      differentiate septic from aseptic post-operative discitis in the lumbar spine by
      means of MR imaging. MATERIAL AND METHODS: The study was a retrospective
      evaluation of 12 patients with prior lumbar discectomy and suspected post
      operative discitis displaying low-back pain and typical MR findings. Six patients
      had elevated serum C-reactive protein (CRP) (septic) and 6 had normal CRP
      (aseptic). We used MR imaging to assess the distribution and degree of changes in
      the disc, in adjacent bone marrow, and in surrounding soft tissue. RESULTS: Of
      the 6 patients with increased CRP levels, 3 had extensive MR changes typical of
      septic post-operative discitis: 1 found soon after surgery; 2 found later. The
      other 3 patients with septic discitis, who were examined in the early post
      operative period, showed MR changes similar to those in the 6 patients with
      aseptic discitis. CONCLUSION: Suspicion of septic post-operative discitis should
      be confirmed by MR imaging, serum CRP, and disc puncture. MR imaging is not
      reliable as the sole method for distinguishing septic from aseptic discitis in
      the early post-operative stage.

PMID- 9529439
TI  - Multiplanar reconstruction in MR imaging of the knee. Comparison with standard
      sagittal and coronal images.
AB  - PURPOSE: To compare standard MR sagittal and coronal imaging of the knee with the
      MR technique of finer sagittal imaging and subsequent reconstruction in any
      plane. MATERIAL AND METHODS: Forty-seven patients took part in the study. Two
      radiologists each made two independent interpretations in every case, based on
      images of: a) 4-mm sagittal and coronal slices; and b) 1.2-mm sagittal slices
      with subsequent reconstruction. RESULTS: We found no significant difference in
      diagnostic efficacy between the two MR techniques. The reconstruction in any
      desired plane involved a potential reduction of 10 min in examination time but an
      increase of approximately 20 min in postprocessing time. CONCLUSION: The use of
      multiplanar reconstruction offered no additional diagnostic value and no saving
      of time.

PMID- 9529440
TI  - Fast spin-echo MR of the articular cartilage in the osteoarthrotic knee.
      Correlation of MR and arthroscopic findings.
AB  - PURPOSE: The objective was to assess the efficacy of fast spin-echo (FSE) imaging
      in the detection of articular cartilage abnormality in osteoarthrosis of the
      knee. MATERIAL AND METHODS: We studied 356 articular surfaces in 73 knees that
      had been examined by both MR imaging and arthroscopy. The MR images were obtained
      with FSE imaging (TR/TE 4200/100) on a 0.5 T unit. The surface abnormalities of
      the articular cartilage that were detected by MR imaging were compared with the
      arthroscopic findings. RESULTS: The overall sensitivity and specificity of MR in
      detecting chondral abnormalities were 60.5% (158/261) and 93.7% (89/95)
      respectively. MR imaging was more sensitive to the higher grade lesions: 31.8%
      (34/107) in grade 1; 72.4% (71/98) in grade 2; 93.5% (43/46) in grade 3; and 100%
      (10/10) in grade 4. The MR and arthroscopic grades were the same in 46.9%
      (167/356), and differed by no more than 1 grade in 90.2% (321/356) and 2 grades
      in 99.2% (353/356). The correlation between arthroscopic and MR grading scores
      was highly significant with a correlation coefficient of 0.705 (p < 0.0001).
      CONCLUSION: FSE sequence was less sensitive to mild cartilage abnormality but
      useful in detecting moderate to severe abnormality and in evaluating the degree
      of articular cartilage abnormality.

PMID- 9529441
TI  - MR imaging in chronic Achilles tendon disorder.
AB  - OBJECTIVES: The primary objective was to compare 4 imaging sequences (T1
      weighted, T2-weighted, proton density, and T1-weighted with gadolinium contrast
      agent enhancement) with regard to intratendinous signal abnormality in patients
      with achillodynia. The secondary objective was to relate the images to the
      clinical symptoms and histopathological findings. MATERIAL AND METHODS: Twenty
      patients (16 men, 4 women, median age 40 years) with chronic achillodynia
      participated in the study. The symptoms prohibited activity and clinical
      examination revealed swelling and tenderness 1.5-6 cm proximal to the Achilles
      tendon insertion. Of the 20 patients: 5 had bilateral achillodynia, 4 had had
      previous contralateral Achilles tendon disorder, and 11 had never had symptoms in
      the contralateral tendon region. These 11 tendons served as controls for
      comparison. MR imaging was performed on a superconductive 1.5 T unit. Both
      Achilles tendons were examined (n = 40) at the same time, and multiple sagittal
      and transversal images were obtained. The corresponding sections on these images
      were visually graded according to both extension and level of MR signal
      intensity. Tissue was obtained for microscopic examination from the most
      symptomatic side in all patients (n = 20). RESULTS: T1-weighted images following
      gadolinium contrast medium enhancement proved to be the best method by which to
      visualize intratendinous signal abnormality. This sequence revealed signal
      abnormality in 24/25 symptomatic tendons and in 1/11 control tendons (p < 0.001).
      Histopathological examination showed an increased noncollagenous extracellular
      matrix and altered fiber structure in the lesions corresponding to the contrast
      enhanced areas. CONCLUSION: Gadolinium enhancement improved the imaging of
      intratendinous signal abnormality on T1-weighted images. There was a high level
      of extracellular glycosaminoglycans, which are highly-fixed negatively-charged
      macromolecules with extreme water-retaining capacity and which may have
      contributed to the enhancement by the gadolinium contrast agent.

PMID- 9529442
TI  - Early esophageal carcinoma. Evaluation of the depth of invasion based on double
      contrast esophagography.
AB  - PURPOSE: The aim of this study was to assess the depth of invasion of early
      esophageal carcinoma (EEC) by means of double-contrast esophagography. MATERIAL
      AND METHODS: The radiological findings of 46 EECs were retrospectively analyzed
      for the following factors that might be related to the depth of invasion: in
      depressed lesions (n = 30): maximum size, surface appearance, sharpness of
      contour, and wall rigidity; and in elevated lesions (n = 16): maximum size,
      height, shape, and wall rigidity. All lesions were surgically or endoscopically
      resected and the radiological findings were compared with the histological
      appearance. RESULTS: In depressed lesions, the size of the surface granules
      correlated very strongly with the depth of invasion (rs = 0.8147). In both
      depressed and elevated lesions, wall rigidity correlated strongly with the depth
      of invasion (rs = 0.7540 and rs = 0.6702 respectively). In depressed lesions,
      sharpness of contour also correlated strongly with the depth of invasion (rs =
      0.6731). The other factors did not correlate with the depth of invasion.
      CONCLUSION: Double-contrast esophagography could provide useful information for
      assessing the depth of invasion of EECs.

PMID- 9529443
TI  - Spiral CT during pharmacoangiography with angiotensin II in patients with
      pancreatic disease. Technique and diagnostic efficacy.
AB  - PURPOSE: To compare the diagnostic efficacy of pancreatic pharmacoangiographic CT
      using angiotensin II with conventional angiographic CT. MATERIAL AND METHODS:
      Eighteen patients with space-occupying pancreatic disease were examined in this
      study. Pharmacoangiographic CT was performed with a 1-3 micrograms/6-ml solution
      of angiotensin II injected through a catheter into the celiac artery during
      spiral CT. RESULTS: In 17 of the 18 (94%) patients, the area of pancreatic
      parenchymal enhancement was the same or larger at pharmacoangiographic CT than at
      conventional angiographic CT. The attenuation value of the pancreatic parenchyma
      was significantly increased at pharmacoangiographic CT (p = 0.0010). Although the
      attenuation value of tumors was also increased on images obtained after the
      injection of angiotensin II, the tumor-to-pancreas contrast was significantly
      greater at pharmacoangiographic CT (p = 0.0479). The mean differences in
      attenuation between tumor and pancreas at angiographic CT with and without
      angiotensin II were respectively 182 HU and 115 HU. CONCLUSION:
      Pharmacoangiographic CT with angiotensin II proved superior to conventional
      angiographic CT in the diagnosis of pancreatic disease. We therefore recommend it
      as a supplementary technique at the angiographic examination of patients with
      suspected pancreatic tumor.

PMID- 9529444
TI  - Sensitivity in detection of hypervascular hepatocellular carcinoma by helical CT
      with intra-arterial injection of contrast medium, and by helical CT and MR
      imaging with intravenous injection of contrast medium.
AB  - PURPOSE: To determine the effectiveness of i.a. contrast-enhanced helical CT and
      of i.v. contrast-enhanced helical CT and MR imaging, in detecting hypervascular
      hepatocellular carcinoma (HCC). MATERIAL AND METHODS: Fifty patients with 125
      hypervascular HCC nodules underwent helical CT both during arterial portography
      (CTAP) and during hepatic arteriography (CTHA). Helical CT and MR imaging of the
      entire liver with i.v. administration of contrast medium were also performed.
      Helical CT images were obtained at 30-33 s (arterial-phase CT) and at 5 min
      (equilibrium-phase CT) after the initiation of an i.v. bolus injection of
      contrast medium. After T1- and T2-weighted spin-echo MR imaging, gradient-echo
      images during breath-holding were obtained prior to and 20 s, 1 min, and 2 min
      after the bolus administration of 0.1 mmol/kg of gadopentetate dimeglumine
      (dynamic MR). The sensitivity and positive predictive value of the various
      techniques were evaluated and compared. RESULTS: In terms of sensitivity for
      hypervascular HCC nodules of less than 1 cm in diameter, CTAP (90%) and CTHA
      (88%) were significantly superior to dynamic MR imaging (44%), arterial-phase CT
      (39%), spin-echo MR imaging (20%), and equilibrium-phase CT (7%) (p < 0.001).
      However, there was no significant difference in the techniques with regard to the
      detection of lesions equal to or more than 2 cm in diameter. CONCLUSION: For
      detecting small hypervascular HCCs, helical CT with i.a. contrast enhancement is
      superior to helical CT and MR imaging with i.v. enhancement.

PMID- 9529445
TI  - Portal and splanchnic haemodynamics in patients with advanced post-hepatitic
      cirrhosis and in healthy adults. Assessment with duplex Doppler ultrasound.
AB  - PURPOSE: To assess portal and splanchnic haemodynamics, and splanchnic vascular
      resistance in patients with advanced post-hepatitic cirrhosis and in healthy
      volunteers, by means of duplex Doppler ultrasound (US). MATERIAL AND METHODS: The
      duplex Doppler US examination was performed in 16 patients with cirrhosis and in
      24 healthy volunteers. We investigated vessel diameters, mean flow velocities,
      and mean blood flows in the portal vein, the superior mesenteric artery (SMA),
      and the splenic artery (SA), and measured the resistive index values of SMA and
      SA. RESULTS: The mean portal venous blood flow in patients with cirrhosis (829 +/
      264 ml/min) was not statistically different from those in the volunteers (734 +/
      194 ml/min). The ratio of the SMA and SA blood flows (621 ml/min) to the portal
      venous blood flow (734 ml/min) was 0.85 in the control subjects. The mean portal
      venous blood flow (1261 ml/min) and the portal venous velocity (14.6 cm/s) were
      higher in the patients with recanalized para-umbilical veins than in the
      volunteers and in the patients without recanalized para-umbilical veins. The SMA
      and SA blood flows were significantly increased in patients with cirrhosis
      compared with volunteers. Splanchnic inflow (the sum of the SMA and SA blood
      flows) was higher than the portal blood flow in patients with cirrhosis except in
      the subjects with recanalized para-umbilical veins. SMA and SA resistive index
      values were significantly higher in these patients than in the volunteers.
      CONCLUSION: Splanchnic blood flow and splanchnic vascular impedance increased
      significantly in patients with advanced post-hepatitic cirrhosis. Splanchnic
      inflow must not exceed portal venous blood flow in patients with recanalized para
      umbilical veins. Portal vein velocity and portal venous blood flow measurements
      alone are not useful parameters for discriminating patients with cirrhosis from
      healthy subjects.

PMID- 9529446
TI  - Electrolytic stent in the normal bile duct. An experimental study.
AB  - PURPOSE: To evaluate and compare changes in the bile-duct wall after the
      insertion of electrolytic and nonelectrolytic stents. MATERIAL AND METHODS: The
      electrolytic stents were composed of 3 different layers (iron, isolating
      polyethylene and tantalum) and were implanted surgically in the bile duct of 8
      healthy pigs. The nonelectrolytic stents were also composed of 3 layers (2 layers
      of tantalum and an isolating layer of polyethylene) and were implanted surgically
      in the bile ducts of 9 healthy pigs. After an observation time of 8 weeks, the
      pigs were killed and the bile ducts were excised and sent for histopathological
      examination. RESULTS: One pig was killed after the procedure owing to
      postoperative complications; all the other pigs survived without complications.
      Migration of the stent to the bowel occurred in 4 pigs. A slight inflammatory
      reaction was seen at histopathological examination in 6 pigs with the
      electrolytic stent and in 6 pigs with the nonelectrolytic stent. There was no
      difference in the specimens from pigs with electrolytic and nonelectrolytic
      stents. CONCLUSIONS: The electrolytic stents did not cause more changes in the
      normal bile-duct wall than the nonelectrolytic stents.

PMID- 9529447
TI  - Magnetic starch microspheres in the MR imaging of hepatic metastases. A
      preclinical study in the nude rat.
AB  - PURPOSE: To evaluate reticular endothelial system-specific magnetic starch
      microspheres (MSM) as an i.v. contrast agent for MR imaging in a model of
      experimental liver metastases. MATERIAL AND METHODS: The study comprised 15 nude
      rats, 7 of which were carrying hepatic metastases from a human colonic cancer.
      The 15 rats were examined at 0.5 T using a T1-weighted spin-echo (SE) sequence
      and a gradient-echo sequence. The examinations were performed before and 15 min
      after the administration of accumulated doses of MSM at 0.25-2.5 mg Fe/kg b.w.
      The images were compared with corresponding serial liver specimens. RESULTS: A
      loss of liver signal intensity was obtained at all MSM dose levels. No metastases
      were detected in the pre-contrast images. The optimum detection rate of hepatic
      metastases was reached with the SE sequence at a dose of 1.0 mg Fe/kg b.w. MSM
      and the diameters of the smallest lesions depicted were 1 mm. However, in the SE
      sequence, the measured lesion-to-liver contrast and liver signal damping were
      highest at the largest dose, indicating a possible image degrading effect of MSM
      at high doses. Administration of MSM as a short bolus over 30 s resulted in
      congestion of the liver with dilatation of the hepatic veins. When MSM was
      instead injected slowly over 5 min, this adverse effect was not seen. CONCLUSION:
      The use of MSM dramatically increased the detection of experimental hepatic
      metastases.

PMID- 9529448
TI  - Peritoneocele and enterocele. Formation and transformation during rectal
      evacuation as studied by means of defaeco-peritoneography.
AB  - PURPOSE: To study, by means of defaeco-peritoneography, the formation and
      transformation of the peritoneocele, with and without an enterocele, during
      rectal evacuation. MATERIAL AND METHODS: Forty-six patients with a peritoneocele
      at defaeco-peritoneography were selected for the study, and examined at three
      different stages: 1) at the start with a contrast-filled rectum; 2) at maximum
      straining; and 3) at rest after rectal evacuation. RESULTS: Fourteen patients had
      a peritoneocele at the start. These peritoneoceles were largest at maximum
      straining and were all still present at rest after rectal evacuation. In 32
      patients defaeco-peritoneography was regarded as normal at the start. At maximum
      straining these patients developed a peritoneocele and 20 of these were still
      present after rectal evacuation. No enterocele was seen at the start. At maximum
      straining 21 patients developed an enterocele and 15 of these were still present
      after rectal evacuation. Liquid in varying amounts was found in the
      peritoneoceles. CONCLUSION: The present study demonstrated that peritoneoceles
      were present at different stages of the defaeco-peritoneographic investigations.
      Peritoneoceles were most frequent and largest at maximum straining. An enterocele
      was present in half of the peritoneoceles at maximum straining, but never at the
      start. Liquid was often present in the peritoneoceles.

PMID- 9529449
TI  - MR features of a 24-year-old gossypiboma. A case report.
AB  - Retained surgical sponges can cause serious diagnostic problems. We report on our
      experience with a piece of gauze, encapsulated for 24 years, that mimicked a soft
      tissue neoplasm, and we describe its MR features.

PMID- 9529450
TI  - The prognostic value of a rare sonographic pattern in Wilson's disease. A case
      report.

PMID- 9529451
TI  - Contrast enhancement in the craniopharyngioma cyst wall caused by irradiation.
AB  - PURPOSE: To report the occurrence, degree, frequency, and duration of contrast
      enhancement in the craniopharyngioma cyst wall as caused by irradiation. MATERIAL
      AND METHODS: Eight patients with cystic craniopharyngiomas had comparable CT or
      MR studies before and after either external irradiation of the cyst (n = 5) or
      32P instillation into the cyst (n = 3). RESULTS: A minimal to marked increase in
      cyst-wall enhancement was seen at 66-157 days after 32P instillation in 3/3 cases
      and at 112-495 days after external irradiation in 3/5 cases. The increased
      enhancement was always associated with a variable interim increase in the
      thickness of the enhanced cyst wall. CONCLUSION: CT or MR imaging after the
      irradiation of cystic craniopharyngiomas usually demonstrated an increase in
      thickness and enhancement in the cyst wall. Such changes may be due to the
      irradiation alone and do not necessarily represent infection or increased
      neoplastic activity. The timing is uncertain as to the earliest possible
      development of such changes and their maximum duration, but they were seen as
      early as 66 days post-irradiation and as late as 495 days post-irradiation.

PMID- 9529452
TI  - Duplex ultrasound in the subclavian steal syndrome.
AB  - PURPOSE: The effect of subclavian steal on the contralateral vertebral flow and
      its possible effect on carotid flow were studied and the US results were compared
      to the angiographic findings. MATERIAL AND METHODS: The study consisted of the
      records of 74 patients with a duplex Doppler finding of subclavian steal
      syndrome. Of these, 48 patients had had both angiography and US of the neck
      arteries and were selected for comparison. For a comparison of the US flow
      values, a control series of 48 was selected from our carotid archive and
      consisted of patients without subclavian steal who had also been examined with
      both US and angiography. RESULTS: Of the 48 patients, 44 had a subclavian steal
      syndrome at angiography, 31 on the left side and 13 on the right. Of the 44, 21
      patients had subclavian occlusion, and 23 stenosis. In 84% of the subclavian
      occlusions, US showed a complete systodiastolic steal and in 16% a partial
      systolic steal, while the corresponding findings for subclavian stenoses were 17%
      and 83%. Of the 48 cases, 4 were not real subclavian steals: 2 had vertebral
      occlusion (1 with a 90% subclavian diameter stenosis) on the side of retrograde
      flow at US and a steal through the vertebral and collateral arteries to the
      spinal arteries; and 2 had a 70% diameter stenosis of the subclavian artery and
      to-and-fro flow in the vertebral artery at angiography. In the 21 cases of
      complete steals, the subclavian diameter stenosis was 97 +/- 8% at angiography,
      and in the 23 partial steals, it was 85 +/- 10%. There was a significant increase
      in contralateral vertebral and common carotid flow in the cases with retrograde
      vertebral flow compared to the vertebral and common carotid flow of the control
      subjects. The retrograde flow values, the ipsilateral vertebral lumen diameter,
      and the flow values in the common carotid arteries were higher in complete steals
      and subclavian occlusions than in partial steals. CONCLUSION: A complete
      vertebral steal at US correlated well with subclavian occlusion and a partial
      steal suggested stenosis of the subclavian artery. There were also flow changes
      in the contralateral vertebral artery and the common carotid arteries that
      compensated for the steal. Retrograde vertebral flow at US was sometimes
      associated with vertebral occlusion in subclavian stenosis without a true
      subclavian steal.

PMID- 9529453
TI  - Development of a huge varix following endovascular embolization for cerebellar
      arteriovenous malformation. A case report.
AB  - We report on the case of a huge varix that developed after the endovascular
      embolization of a cerebellar arteriovenous malformation (AVM) with a single
      drainer. A 21-year-old male presented with trigeminal neuralgia which was caused
      by the dilated drainer of the AVM. A varix was found at the basal vein of
      Rosenthal 2 months after an initial stage of embolization with polyvinyl alcohol
      particles; it diminished after the surgical extirpation of the AVM. The varix
      formation might have been facilitated by the stenosis in the vein of Galen and by
      the dynamic changes that followed the embolization. This rare complication should
      be kept in mind when embolization is performed for AVMs with impaired venous
      outlets.

PMID- 9529454
TI  - Reliability of Doppler ultrasound in follow-up studies.
AB  - PURPOSE: To evaluate the reliability of repeat Doppler US measurements. MATERIAL
      AND METHODS: Nine radiologists conducted two sets of Doppler US measurements on a
      healthy volunteer, with a time interval of 9 months. Peak systolic velocity
      (PSV), resistance index (RI), and pulsatility index (PI) were measured 10 times
      in 4 arteries. RESULTS: There was considerable intra- and inter-observer
      variation both at baseline and 9 months later. The PSV values from the carotid
      artery varied from 0.27 m/s to 1.95 m/s in February and from 0.22 m/s to 1.38 m/s
      in November. The RI values from the renal artery ranged from 0.44 to 0.71 in
      February and from 0.41 to 0.67 in November. The results of the 9-month follow-up
      varied markedly too. Best reproducibility was achieved by highly experienced
      radiologists both at baseline and 9 months later. CONCLUSION: The short-term and
      long-term reliability of Doppler US was poor when the measurements were performed
      by a heterogeneous group of radiologists. The RI and PI measurements were
      somewhat more reliable than the PSV measurements and are recommended for use in
      follow-up studies.

PMID- 9529455
TI  - Costs of plain-film radiography in a partially digitized radiology department. An
      activity-based cost analysis.
AB  - PURPOSE: The aim of the study was to analyse the costs of computed radiography
      (CR) as part of a small picture archiving and communication system (mini-PACS),
      and to compare these costs with those of conventional analogue radiography using
      activity-based accounting (ABC). MATERIAL AND METHODS: The study was conducted at
      the Central Hospital of Vaasa where in 1993 the Radiology Department acquired a
      mini-PACS with a CR reader, a chest CR unit, and a CT unit as digital image
      processing modalities. Of altogether 34140 plain-film examinations, 3/4 were made
      with CR and stored mostly on film, and 1/4 were made with conventional analogue
      radiography. The costs and activities of these two modes were analysed by means
      of the ABC method which identifies and allocates indirect costs in radiological
      procedures. RESULTS: The costs of CR imaging were 9% higher than those of
      conventional radiography. The costs of the chest CR unit were equal to those of
      conventional radiography. The difference was due to higher investment costs in
      digital image processing. The time gained from a reduction in the number of
      retakes did not shorten the time spent by patients in the examination room, and
      its effect on film costs was minimal. CONCLUSION: In planning the step-by-step
      transition of conventional film-based analogue radiography to fully digitized
      radiography, it should be noted that films are still used in the transition
      period and that this is associated with higher costs than in the previous system
      of conventional analogue plain-film imaging.

PMID- 9529456
TI  - Comprehensive child health. Is it in the picture?

PMID- 9529457
TI  - "Bet you I will!" Risk or experimental behavior during adolescence?

PMID- 9529458
TI  - Changes in the daily practice of primary care for children.
AB  - BACKGROUND: The environment in which medicine is practiced has changed in the
      past 2 decades, but little information has been available on how the day-to-day
      practice of primary care for children has changed during this period. OBJECTIVE:
      To identify aspects of primary care practices for children that are undergoing
      substantial changes. DESIGN: Analysis of National Ambulatory Medical Care Surveys
      from 1979 to 1981, 1985, and 1989 to 1994. PARTICIPANTS: Primary care
      practitioners recorded data on 58,488 child visits. MAIN OUT COME MEASURES:
      Characteristics and insurance status of children, physician activities during
      visits, and disposition after visit. RESULTS: Child visits to primary care
      physicians increased by 22% between 1979 and 1994. The mean age of children
      visiting primary care physicians decreased from 6.7 years in 1979 to 5.7 years in
      1994 (P for trend, < .001). The ethnic diversity of child visits increased
      primarily as a result of an increasing proportion of visits by Hispanic (6.0% in
      1979 to 12.6% in 1994, P for trend, < .001) and Asian patients (1.6% in 1979 to
      4.1% in 1994, P for trend, < .001). Medicaid and managed care increased
      dramatically as sources of payment. Changes in physician activities included an
      increase in some preventive services, changes in the most commonly encountered
      medications, and an increased mean duration of patient visits (11.8 minutes in
      1979 to 14.2 minutes in 1994, P for trend, < .001). CONCLUSIONS: These data may
      assist in the development of educational and research initiatives for physicians
      caring for children. The declining proportion of adolescent visits may present
      physicians with challenges in the care of adolescents. Physician prescribing
      practices showed changes without evidence of a benefit to child health. The
      increased ethnic diversity and provision of preventive services were associated
      with an increased mean duration of primary care visits. The increased duration of
      child visits may conflict with the managed care emphasis on physician
      productivity.

PMID- 9529459
TI  - The changing pattern of substance abuse in urban adolescents.
AB  - OBJECTIVES: To determine the prevalence of specific drug use in adolescents
      attending an adolescent health clinic and to compare current rates with a similar
      previous study. DESIGN: Blinded and anonymous urine samples obtained from
      patients presenting for routine health care were tested for the presence of
      cannabinoids, phencyclidine (PCP), amphetamines, opiates, and cocaine. SETTING:
      Adolescent medicine outpatient clinic. PATIENTS: Patients were between 12 and 21
      years of age. Specimens from 1313 patients in 1995 to 1996 and 1312 patients in
      1989 to 1990 were tested. MAIN OUTCOME MEASURES: Current drug use rates were
      compared with a similar screening of patients conducted in 1989 to 1990.
      Comparisons between studies were made on the basis of specific drug, age, and
      sex. RESULTS: For the most recent patient group, 14% were positive for 1 or more
      drugs and 13% were positive for cannabinoids. Males were significantly more
      likely to test positive for drug use than females. The oldest adolescents were
      more likely to test positive for drug use than younger adolescents. Comparing the
      2 study year cohorts, patients tested recently were significantly more likely to
      have urine tests positive for at least 1 drug and cannabinoids in particular and
      less likely to have urine tests positive for cocaine. CONCLUSIONS: There has been
      an increase in positive urine tests in patients seen in our ambulatory clinic,
      with a strong shift toward cannabinoids and a shift away from cocaine.
      Practitioners need to be aware that drug use patterns in adolescents can shift
      relatively abruptly and counseling should be targeted to current drug use
      patterns.

PMID- 9529460
TI  - Reducing missed opportunities to vaccinate during child health visits. How
      effective are parent education and case management?
AB  - BACKGROUND: At child health visits, immunizations that are due are frequently not
      given. Increased parent understanding of and demand for immunizations may
      influence providers to not miss these opportunities. OBJECTIVE: To assess, as
      part of a larger study of effectiveness of parent education and case management
      (CM) in raising immunization rates, the intervention's effectiveness at reducing
      missed opportunities to vaccinate during child health visits. METHODS: A
      representative sample of African American newborns and their families from south
      central Los Angeles, Calif, were randomly assigned to a control or a CM group and
      observed during the first year of life. Case managers visited and telephoned
      parents, educating them on the benefits and safety of immunizations, and
      encouraging them to request immunizations from providers. When the children were
      at least 1 year of age, parents were interviewed and provider records were
      abstracted. RESULTS: Complete records were abstracted for 126 controls and 129 CM
      group children. For these children, 1092 visits were documented where
      immunizations were due. Missed opportunities to vaccinate occurred at more than
      50% of visits. Case management was associated with a modest reduction in the
      percentage of visits with missed opportunities in the bivariate analysis but not
      after adjustment for other covariates. In a logistic regression model, missed
      opportunities were more frequent at visits with private than public physicians
      and at acute illness than well-child visits. Missed opportunities were less
      frequent among children with a history of at least 1 cancelled appointment, and
      for visits of children with mothers who smoked. CONCLUSIONS: Missed opportunities
      were minimally influenced by a home visitation and parent education program. They
      are primarily determined by issues under the control of the provider. Family- and
      child-related characteristics, however, do influence the likelihood of a missed
      opportunity occurring independent of provider factors.

PMID- 9529461
TI  - Prevalence of clinical sinusitis in young children followed up by primary care
      pediatricians.
AB  - OBJECTIVE: To determine the proportion of young children seen in primary care
      pediatric practices who meet clinical criteria for the diagnosis of sinusitis,
      and variations in the management of these patients' conditions. DESIGN:
      Observational cohort study. SETTINGS: Pediatric practices in the Seattle, Wash,
      area participating in the Puget Sound Pediatric Research Network, a regional
      practice-based research organization. PATIENTS: Children, 1 to 5 years old,
      presenting for any reason to participating practices. METHODS: Parents of all
      1307 eligible children completed a survey specifically detailing the presence of
      nasal congestion or discharge and daytime cough, the duration of these symptoms,
      and whether the symptoms were improving. For patients meeting clinical criteria
      for sinusitis (nasal congestion and daytime cough persisting for > 9 days without
      improvement), the pediatrician recorded the presence/severity of other signs and
      symptoms, and the treatment prescribed. Severity of symptoms was reassessed using
      telephone interviews with parents at 48 to 72 hours, and again at 10 to 14 days,
      after the office visit. Study data were collected during 1-week to 3-week blocks
      at each office site during the winter months. RESULTS: Data were collected on
      1307 children; 121 had persistent respiratory symptoms meeting criteria for a
      diagnosis of sinusitis (9.3%, 95% confidence interval, 7.7%-10.9%). Patients who
      presented with cold/cough symptoms were significantly more likely to meet
      criteria for sinusitis than those who came for any other reason (17.3% vs 4.2%,
      respectively, P < .001). A physician study form was completed on 87 children with
      persistent symptoms; antibiotics were prescribed for 68 (78%) of these patients.
      Antibiotic-treated patients were more likely to have symptoms lasting longer than
      29 days (P = .004) and to have purulent nasal discharge (P = .03), and were
      judged to be sicker at enrollment (P = .001) than untreated children. A
      concurrent otitis media was diagnosed in 40 (46%) of 87 patients; if the
      proportion of children with otitis media is excluded, 5% of children 1 to 5 years
      old who are seen in primary care pediatrics might be expected to receive
      antibiotics exclusively for a diagnosis of sinusitis. At 24 to 48 hours and at 10
      to 14 days after the clinic visit, a trend was noted toward more rapid
      improvement among those children who were treated with antibiotics. CONCLUSION:
      When the criteria are strictly adhered to, only a small proportion of young
      children seen during the winter months in primary care pediatric practices will
      be diagnosed with sinusitis.

PMID- 9529462
TI  - Management of infants of diabetic mothers.
AB  - OBJECTIVE: To describe the clinical outcome of infants born to mothers with
      gestational diabetes mellitus (GDM) and preexisting insulin-dependent diabetes
      mellitus (IDDM). SETTING: A tertiary care regional perinatal center with a
      specialized diabetes-in-pregnancy program. DESIGN: Case series. RESULTS: Five
      hundred thirty infants were born to 332 women with GDM and 177 women with IDDM.
      Thirty-six percent of these 530 newborns were large for gestational age, 62% were
      appropriate for gestational age, and only 2% were small for gestational age.
      Seventy-six (14%) of all infants were born before 34 weeks' gestation, 115 (22%)
      between 34 and 37 weeks of gestation, and 339 (64%) at term. Two hundred thirty
      three infants (47%) were admitted to the neonatal intensive care unit due to
      respiratory distress syndrome (RDS), prematurity, hypoglycemia, or congenital
      malformation. Hypoglycemia (more common among infants of maternal diabetic
      classes C through D-R) was documented in 137 (27%) of all newborns. One hundred
      eighty-two infants (34%) had RDS of varying severity. Polycythemia (5% of
      infants), hyperbilirubinemia (25%), and hypocalcemia (4%) were other morbidities
      present. Two hundred forty-four infants were admitted for routine care and
      enteral feedings. Forty-three of these newborns required subsequent transfer to
      the neonatal intensive care unit for treatment of hypoglycemia (16 cases), RDS
      (19 cases), or both (8 cases). Routine care failures were more common among
      infants whose mothers had advanced diabetes, but less frequent among breast-fed
      infants. CONCLUSIONS: With modern management, fewer morbidities can be expected
      in infants of diabetic mothers. Those infants born to women with IDDM remain at
      risk for hypoglycemia, which can be treated in one half of the cases by enteral
      feedings alone. The majority of cases of RDS are mild and require short
      admissions to special care nurseries. Optimal care of infants of diabetic mothers
      is based on prevention, early recognition, and treatment of common conditions.
      Severe congenital malformations, significant prematurity, RDS, recurrent
      hypoglycemic episodes, and asymptomatic infants of women with advanced IDDM
      should be admitted to special care nurseries. Breast-feeding among women with GDM
      and IDDM should be encouraged.

PMID- 9529463
TI  - Listening to parents. A national survey of parents with young children.
AB  - OBJECTIVE: To document the child-rearing needs and pediatric health care
      experiences of parents with children from birth to 3 years old. DESIGN: A
      nationally representatives sample of 2017 parents with children younger than 3
      years using a 25-minute structured telephone questionnaire. Interviews were
      completed by 68% of the screened eligible respondents. The margin of sampling
      error for results at the 95% confidence level was +/- 3 percentage points.
      RESULTS: Seventy-six percent of children younger than 3 years were reported by
      parents to be in excellent health; 88% had a regular source of pediatric health
      care. Seventy-one percent of parents who received special pediatric services
      rated their child's physician as excellent in providing good health care. Seventy
      nine percent of parents reported they could use more information in at least 1 of
      6 areas of child rearing, and 53% wanted information in at least 3 areas. Forty
      two percent had talked with their child's physician about "nonmedical" concerns;
      39% of parents read to or looked at a picture book with their child on a daily
      basis; 51% of parents set daily routines for meals, naps, and bedtime. Breast
      feeding and reading to the child on a daily basis were much more likely if a
      physician encouraged parents to do so. CONCLUSIONS: Most parents view the
      pediatric health care system as meeting the physical health needs of their young
      children. Parents want more information and support on child-rearing concerns,
      yet pediatric clinicians often fail to discuss nonmedical questions with them.
      The interventions of pediatric clinicians can positively affect parental
      behavior. Pediatric practices should consider creative ways to reconstitute and
      augment their current services and systems of care.

PMID- 9529464
TI  - African American mothers in south central Los Angeles. Their fears for their
      newborn's future.
AB  - OBJECTIVE: To determine what African American mothers in a low-income community
      fear for their newborn's future. DESIGN: An interview survey was conducted with
      mothers of recently born infants randomly sampled from birth certificate records
      in the spring of 1994 in 10 postal codes in the Compton Health District in south
      central Los Angeles, Calif, with high concentrations of low-income African
      American children. Among 522 eligible mothers, 419 (80%) were interviewed.
      Children were an average of 17.7 days old at the time of the interview. MAIN
      OUTCOME MEASURE: The open-ended survey item, "What is your biggest fear for
      [child's name] growing up?" Mothers were prompted to give more than 1 answer.
      Responses were classified into 16 categories. RESULTS: Thirty-nine percent of the
      mothers reported a fear of gangs, violence, or both. The largest other response
      categories included disease, illness, and health problems (17%); drugs and
      alcohol (15%); growing up in the local environment (10%); and society and the
      world in general (6%). Fifty percent of the mothers of boys reported a fear of
      gangs, violence, or both compared with 28% of the mothers of girls (P < .001).
      CONCLUSIONS: More than half the fears are in the medical and public health
      domains. Some involve traditional health concerns (e.g., disease), while others
      are problems that the health professions have been addressing more recently
      (e.g., violence). The American Academy of Pediatrics has recommended counseling
      families about violence prevention and the prevention of firearm injuries. While
      this study shows that many mothers are concerned about these subjects, we need a
      greater understanding of what role physicians can play in helping their patients
      (and their patients' families) address violence in their lives.

PMID- 9529465
TI  - Effect of HIV counseling and testing on sexually transmitted diseases and condom
      use in an urban adolescent population.
AB  - OBJECTIVE: To determine whether human immunodeficiency virus (HIV) counseling and
      testing has an effect on reducing subsequent risk behaviors in those tested, to
      evaluate stability in condom use over time, and to determine whether self
      reported frequency of condom use relates to the incidence of sexually transmitted
      diseases (STDs). DESIGN: Cohort study with 2-year follow-up. SETTING: An urban
      adolescent-medicine clinic. PARTICIPANTS: A random sample of 149 patients (118
      female and 31 male adolescents) with a mean (+/- SD) age of 16.4 +/- 1.51 years
      were selected from a cohort of 500 patients at high risk for HIV infection. The
      patients had received a risk behavior questionnaire during pretest counseling for
      HIV testing. They were divided into 3 groups, identified by the letter F, S, or
      R, based on their self-report of frequency of condom use at enrollment: 24% used
      condoms frequently/always (F); 40%, sometimes (S); and 36%, rarely/never (R). One
      hundred twenty-six patients (85%) made return visits. INTERVENTION: HIV
      counseling and testing. MAIN OUTCOME MEASURES: Medical record documentation of
      STDs before and after HIV testing, and self-reported condom use frequency.
      RESULTS: Before HIV testing, all 3 condom use groups had a similar frequency of
      STD visits per month. The number of STD visits per month did not decrease
      significantly in the posttest period for either the total group or each of the 3
      subgroups. Also, most patients (F, 67%; S, 44%; R, 53%) in each of the 3
      subgroups had shifted unfavorably to rarely/never (R) condom use within the month
      before their follow-up visit. Only 24% (8 patients) of those in the initial
      frequently/always (F) group reported continued frequent condom use. CONCLUSIONS:
      As has been found in adult studies, single-dose interventions such as HIV
      counseling and testing did not seem to reduce HIV risk behaviors in our sample of
      high-risk adolescent patients. None of the 3 groups showed a significant decrease
      in STDs after HIV testing and counseling. Also, our adolescent patients reported
      widely varying condom use frequency over time, yet the incidence of STDs did not
      correlate with self-reported condom use.

PMID- 9529466
TI  - Compliance with penicillin prophylaxis in patients with sickle cell disease.
AB  - OBJECTIVE: To assess factors related to compliance with penicillin prophylaxis
      among patients with sickle cell disease. DESIGN: Prospective case series.
      SETTING: Urban pediatric medical center where universal penicillin prophylaxis is
      recommended for all patients with any sickle cell hemoglobinopathy independent of
      age. PARTICIPANTS: Eligible patients with sickle cell hemoglobinopathies were
      enrolled in either the emergency department or the sickle cell clinic. MAIN
      OUTCOME MEASURES: Compliance was assessed by structured interview and by urine
      assay with an established method (Micrococcus luteus with disk diffusion) that
      detects excreted penicillin up to 15 hours after each dose administration.
      RESULTS: Of the 159 patients actively followed up at the sickle cell center, 123
      (77.3%) eligible patients were enrolled. Reported compliance by structured
      interview (> or = 1 dose of penicillin V potassium within 15 hours of enrollment)
      was 83 of 123 patients (67.5%; 95% confidence interval, 59.2%-75.8%), whereas
      measured compliance as determined by urine assay was 53 of 123 patients (43.1%;
      95% confidence interval, 31.3%-51.7%). Measured compliance was significantly
      greater in patients younger than 5 years than in those older than 5 years (25/41
      [61%] vs 28/82 [34%], respectively; P = .004), and was significantly greater in
      patients with private insurance than in those with public insurance (17/28 [61%]
      vs 33/90 [37%], respectively; P = .02). Measured compliance was not significantly
      associated with sex, site of recruitment, hemoglobinopathy, or chief complaint in
      the emergency department. CONCLUSIONS: Measured compliance was poor, and patients
      and/or their families frequently misrepresented their compliance when
      interviewed. These data suggest that efforts are necessary to improve overall
      compliance, and they identify groups at greatest risk for noncompliance.

PMID- 9529467
TI  - Neonatal circumcision. Randomized trial of a sucrose pacifier for pain control.
AB  - OBJECTIVE: To assess the effectiveness of oral sucrose via a nipple compared with
      no treatment and dorsal penile nerve block (DPNB) for alleviating pain in
      neonatal circumcision. DESIGN: Randomized control trial. Data analysis performed
      by investigators blinded to the 3 treatment groups. SETTING: University teaching
      hospital, General Care Nursery. PATIENTS: One hundred nineteen full-term male,
      normal birth weight neonates, 12 hours old or older. INTERVENTIONS: No treatment
      (our standard care), DPNB, or oral sucrose prior to circumcision. MAIN OUTCOME
      MEASURES: Differences between groups in heart rate and oxygen saturation changes
      from baseline during specified intervals of the circumcision procedure.
      Differences between groups in loss of data due to episodes of excessive motion.
      RESULTS: Sucrose gave significant (P < .001) pain relief compared with the no
      treatment control throughout most of the circumcision and particularly in the
      early stages of the procedure. Overall, the average difference in the elevation
      of heart rates during the circumcision operative procedure among the 3 groups and
      the 95% confidence intervals (CIs) were as follows: control vs DPNB, 27.1
      beats/min (17.6, 36.6) and control vs sucrose, 9.7 beats/min (0.1, 19.3).
      Furthermore, newborns who received either DPNB or sucrose had less loss of oxygen
      saturation data due to excessive motion during the procedure than the no
      treatment controls. The total percentages of lost data due to excessive motion in
      the 3 groups were 31% for control, 10% for DPNB, and 8% for sucrose. Relative
      risk and 95% CIs were: DPNB vs control, 0.32 (0.23, 0.43); sucrose vs control,
      0.26 (0.18, 0.36). Differences in oxygen saturation among the 3 groups during the
      circumcision operative procedure were statistically (P < .001), but perhaps not
      clinically, significant. However, the analysis did not include missing data due
      to excessive motion, which occurred predominantly in the no-treatment control
      group. CONCLUSION: Sucrose on a pacifier is an inexpensive and effective method
      for pain relief in neonatal circumcision when DPNB is not desirable.

PMID- 9529468
TI  - Vaccine-associated liability risk and provider immunization practices.
AB  - OBJECTIVE: To explore the effect of concern about vaccine-associated malpractice
      litigation on provider immunization practices and attitudes. DESIGN: A cross
      sectional mail survey. PARTICIPANTS: One thousand one hundred sixty-five
      pediatricians and 1849 family physicians. MAIN OUTCOME MEASURES: Physicians'
      perceptions of the legal and financial risks of providing immunizations and of
      the liability protection afforded by state programs and their current
      immunization practices. RESULTS: The response rate was 72% for pediatricians and
      63% for family physicians. Overall, less than 30% of the respondents believed
      that federal and state programs protect them against vaccine-related lawsuits,
      with pediatricians more likely to believe so (32% vs 21%, P < .0001).
      Pediatricians were also more likely than family physicians to believe that the
      diphtheria, tetanus, and pertussis vaccine could be administered safely to
      children with a family history of seizures, a minor respiratory tract illness, or
      a previous local reaction to the vaccine. Liability issues were not significantly
      associated with any of the outcome variables, except that those physicians who
      believed that the whole-cell diphtheria, tetanus, and pertussis vaccine increased
      their risk for lawsuits were less likely to indicate that the diphtheria,
      tetanus, and pertussis vaccine was safe for children with a family history of
      seizures (P < .001). CONCLUSIONS: Liability-related variables were not
      independently associated with most immunization behaviors examined. This raises
      the question as to whether physicians cite liability as a reason for not
      immunizing children with acute and chronic illnesses, when their concerns are
      actually otherwise. These data suggest that educational efforts focused on
      liability issues alone will have little effect on inappropriate delaying of
      immunization for these children. Rather, education is needed regarding
      inappropriate contraindications themselves.

PMID- 9529470
TI  - Clinical teaching rounds. A case-oriented faculty development program.
AB  - OBJECTIVE: To improve clinical teaching with emphasis on improving provision of
      feedback through a faculty development series modeled on clinical rounds. METHOD:
      Seven 1-hour conferences were held for the pediatric faculty during the academic
      year 1994-1995. Clinical rounds were emulated, with a simulated learner
      functioning as the patient with a chief complaint of some instructional problem.
      The conferences progressed from discussion about teaching in a particular
      situation, to videotapes of clinical teaching, and finally to live clinical
      teaching. Evaluation of the conferences was assessed by attendance records,
      participants' evaluations of the conferences, and comparing student and resident
      evaluations of faculty who attended (i.e., those who attended > or = 2) with
      faculty who did not attend. Comparisons were made for the academic year before
      and after the conferences using paired t tests. RESULTS: Forty percent of the
      faculty attended 2 or more conferences. Mean conference ratings were 4.00 to
      4.35, (1 is poor; 5, excellent). Faculty who attended had a significant
      improvement in ratings for feedback (P = .01) and overall teaching effectiveness
      (P = .04). Ratings for faculty who did not attend did not change. CONCLUSION:
      These conferences were well received by the faculty and are an effective way to
      improve clinical teaching.

PMID- 9529469
TI  - Hyponatremic seizure in a child using desmopressin for nocturnal enuresis.
AB  - BACKGROUND: Intranasal desmopressin has been used extensively to treat primary
      nocturnal enuresis. While it has proven to be a safe, effective agent for many
      who are affected by this condition, the potential for complications exists.
      OBJECTIVES: To report a case of severe hyponatremia associated with a generalized
      tonic-clonic seizure in a 10-year-old boy who had been receiving intranasal
      desmopressin nightly for nocturnal enuresis and to briefly review therapeutic
      options for nocturnal enuresis; and to present the role of desmopressin. SETTING:
      Georgetown University Medical Center, Washington, DC. INTERVENTION: Fluid
      restriction and intravenous isotonic saline solution with 5% dextrose was
      administered to raise the serum sodium level. OUTCOME: Prevention of further
      seizures with normalization of serum sodium levels without any obvious
      neurological sequelae. CONCLUSIONS: This case illustrates the importance of
      weighing the benefits and risks of intranasal desmopressin therapy.

PMID- 9529471
TI  - Radiological case of the month. Neonatal brain abscess caused by Citrobacter
      diversus.

PMID- 9529472
TI  - Picture of the month. Cervical myelomeningocele.

PMID- 9529473
TI  - Pathological case of the month. Immature ovarian teratoma with gliomatosis
      peritonei.

PMID- 9529474
TI  - Corporal punishment and antisocial behavior.

PMID- 9529475
TI  - Two emerging perspectives of parental spanking from two 1996 conferences.

PMID- 9529477
TI  - Advances in the surgical treatment of oesophageal cancer.

PMID- 9529476
TI  - Drawing conclusions about temporal order.

PMID- 9529478
TI  - Rationing and surgery: setting boundaries.

PMID- 9529480
TI  - Adjuvant therapy for resectable rectal and colonic cancer.
AB  - BACKGROUND: Recurrence of rectal and colonic carcinoma remains substantial
      despite apparently curative surgery. Adjuvant therapy has been applied to improve
      prognosis. METHODS: This review evaluates the use of adjuvant therapy in the
      management of resectable rectal and colonic carcinoma. It assesses critically the
      evidence supporting the addition of radiotherapy, chemotherapy, chemoradiotherapy
      and other treatment modalities to optimal surgery. RESULTS: In the case of rectal
      tumours, preoperative is more effective than postoperative radiotherapy; It can
      significantly reduce the incidence of local tumour recurrence. A number of trials
      have tended towards showing a survival advantage and a recent large randomized
      trial has shown a significant improvement in survival in patients with Dukes C
      tumours. Postoperative chemoradiotherapy is associated with a survival benefit
      and is standard therapy in the USA, although it is associated with increased
      toxicity. The effectiveness of preoperative chemoradiotherapy is currently being
      investigated. Postoperative fluorouracil-containing chemotherapy has resulted in
      a survival advantage in patients with Dukes C colonic tumours; such therapy may
      be administered either systemically or intraportally. The evidence of benefit
      with rectal tumours is more limited. Immunotherapy has been studied to a limited
      extent and the use of a tumour-directed monoclonal antibody has produced a
      survival advantage in a single trial. CONCLUSION: Preoperative radiotherapy and
      postoperative chemoradiotherapy can produce a survival advantage in patients with
      Dukes C rectal carcinoma and reduce local recurrence. Postoperative fluorouracil
      containing chemotherapy can produce a survival advantage in those with Dukes C
      colonic cancer. The optimal use and combination of adjuvant therapy remains
      uncertain.

PMID- 9529479
TI  - Management of faecal incontinence following obstetric injury.
AB  - BACKGROUND: Faecal incontinence is common in women and the major aetiological
      factor is childbirth. Increasing numbers of women with faecal incontinence are
      presenting to surgical clinics. METHODS: A literature review was performed on
      Medline database for English language publications an obstetric injury. The
      incidence, presentation, assessment and treatment of faecal incontinence
      following obstetric injury were evaluated. RESULTS AND CONCLUSIONS: Third-degree
      tear occurs in association with less than 1 per cent of vaginal deliveries, but
      occult sphincter injury occurs at one-third of deliveries and may be significant
      in later life. Incontinence may result from sphincter damage or nerve injury, or
      both. Risk factors for these injuries can be identified. Clinical evaluation,
      anorectal physiology and endoanal ultrasonography allow accurate planning of
      subsequent surgery. Overlapping anterior anal sphincter repair provides
      symptomatic control of continence in 80 per cent of patients. Repair of an acute
      anal sphincter injury after a third-degree tear is controversial and a defined
      policy should be agreed between obstetric and colorectal teams.

PMID- 9529481
TI  - Endoprostheses for colonic strictures.
AB  - BACKGROUND: Patients who present with large bowel obstruction often undergo
      emergency surgical intervention with its attendant risk of morbidity and death. A
      colostomy may be inevitable and this detracts from the patient's quality of life,
      especially when palliation is the only option. METHODS: This review examines the
      possibility of a more conservative approach using metallic stents to relieve
      colonic obstruction, either as the first stage of a curative surgical procedure
      or for palliation without surgery. The various stents available are examined.
      RESULTS: Case reports show that relief of obstruction can be achieved in over 80
      per cent of patients, allowing subsequent elective surgery or achieving
      palliation for several months. Complications are rare but include colonic
      perforation, particularly when predilatation of the stricture has to be
      performed. Such complications are generally recognized early and patients can
      proceed to surgery and colostomy, as would previously have been conventional
      treatment; on occasion a small leak may be treated conservatively with success.
      The advent of newer endoprostheses which do not require active dilatation may
      improve the rate of successful deployment and lessen the risk of perforation.
      CONCLUSION: The development of new endoprostheses has allowed their adaptation
      for use in the colon and, perhaps, the distal small bowel. The technology is
      evolving rapidly and warrants serious consideration in selected patients with
      large bowel obstruction before embarking on surgery. There is an urgent need for
      a controlled trial to establish whether such intervention for malignant
      strictures, potentially curable by surgery, leads to an increased risk of
      metastatic disease.

PMID- 9529482
TI  - An 8-year experience of hepatic resection: indications and outcome.
AB  - BACKGROUND: Most reports highlighting decreasing operative morbidity and
      mortality rates following hepatic resection have focused on the management of
      metastatic disease. Information on the full range of hepatic disease is lacking.
      METHODS: The indications for hepatic resection in a specialist hepatobiliary unit
      have been reviewed and the operative morbidity and mortality rates assessed.
      RESULTS: Among 129 patients undergoing 133 hepatic resections between October
      1988 and September 1996, the principal indication for resection was hepatic
      malignancy (102 resections), metastatic in 66 cases. Other indications included
      contiguous tumour (n = 20), primary tumour (n = 16) and benign disease (n = 31).
      Some 116 procedures were classical anatomical resections. Blood transfusion was
      required in 40 per cent of cases but major morbidity occurred in 20 per cent.
      There were six deaths following surgery, five of which were due to hepatic
      failure and followed resection for malignancy or trauma. The 3-year survival rate
      in patients resected for colorectal metastases was 65 per cent. CONCLUSION: This
      experience has demonstrated an increasing role for hepatic resection in a wide
      variety of hepatobiliary pathologies. Despite the low postoperative mortality
      rate, the significant risk of complications in the postoperative period serves to
      emphasize the need for careful selection of patients for such surgery, which
      should be undertaken in specialist centres.

PMID- 9529483
TI  - Prediction of resectability of pancreatic malignancy by computed tomography.
AB  - BACKGROUND: The accuracy of computed tomography (CT) in predicting resectability
      of pancreatic malignancy has been questioned recently and alternative methods
      have been recommended. METHODS: To determine the accuracy of CT for predicting
      resectability and its influence on survival, a standard protocol for performing
      CT and reporting the results was developed and then compared retrospectively with
      the ability of one surgeon to perform a resection during 1989-1994. Postoperative
      survival was determined. RESULTS: Of 88 consecutive patients 35 (40 per cent) had
      CT-resectable disease and 53 (60 per cent) had CT-irresectable disease. Twenty
      one patients were excluded because of advanced disease or poor performance
      status. Of the remaining 67 patients, 47 (70 per cent) had pancreatic ductal
      adenocarcinoma and 20 (30 per cent) had ampullary adenocarcinoma, of whom 32 had
      a resection, 32 had a palliative bypass and three had only a staging laparoscopy.
      The sensitivity and specificity for computed tomographic prediction of
      resectability were 72 and 80 per cent respectively. The positive predictive value
      was 77 per cent and the negative predictive value 76 per cent. There were seven
      false-positive and nine false-negative findings. Survival was more dependent on
      whether or not resection was performed than on computed tomographic
      predictability of resection. CONCLUSION: CT was reasonably accurate in predicting
      resectability but cannot be relied on entirely, requiring an improvement in
      staging methods for pancreatic malignancy.

PMID- 9529484
TI  - Bile duct obstruction due to portal biliopathy in extrahepatic portal
      hypertension: surgical management.
AB  - BACKGROUND: Varices can develop in and around the bile duct in the presence of
      portal hypertension, especially when it is caused by extrahepatic portal vein
      thrombosis. The term 'portal biliopathy' is used to describe changes in the bile
      duct due to these varices, which may cause bile duct obstruction. This paper
      reviews experience of the surgical management of patients with symptomatic portal
      biliopathy. METHODS: Nine patients with extrahepatic portal vein obstruction with
      symptomatic portal biliopathy. were reviewed retrospectively. RESULTS: Eight
      patients presented with jaundice, two had abdominal pain and one had recurrent
      cholangitis. Endoscopic retrograde cholangiography revealed abnormality of the
      bile duct wall, with stricture in eight patients and bile duct calculi in two.
      Portasystemic shunting relieved jaundice in five of seven patients, and in two a
      second-stage hepaticojejunostomy was required. CONCLUSION: Symptomatic biliary
      obstruction in patients with extrahepatic portal hypertension may be relieved by
      a portasystemic shunt. Rarely biliary bypass may be required and is rendered
      safer by previous portasystemic shunting to decompress the pericholedochal
      varices. A direct approach to the biliary tract without a preliminary shunt may
      be hazardous and is frequently unnecessary.

PMID- 9529485
TI  - Laparoscopic drainage of liver abscesses.
AB  - BACKGROUND: The mainstay of the management of liver abscesses has been
      intravenous antibiotics and radiologically guided percutaneous drainage. However,
      not all abscesses are treated successfully in this way, and some require surgical
      drainage. Laparoscopic drainage of liver abscesses may be an alternative to open
      surgical drainage. METHODS: Twenty consecutive patients with liver abscesses
      treated by laparoscopic drainage in combination with intravenous antibiotics were
      studied prospectively. Fifteen had had failed percutaneous drainage previously.
      RESULTS: There were 13 right lobe and seven left lobe abscesses ranging from 6 to
      25 cm in diameter. Mean operating time was 38 min. Seventeen patients were
      drained successfully. Three patients developed recurrent symptoms of which two
      resolved with conservative measures, but one required a second laparoscopic
      procedure. There were no intraoperative or other postoperative complications in
      the 20 patients. Follow-up ranged from 5 to 12 months. CONCLUSIONS: Laparoscopic
      drainage of liver abscesses, in combination with systemic antibiotics, is a safe
      and viable alternative in all patients who require surgical drainage following
      failed medical or percutaneous treatment, and in those with large abscesses.

PMID- 9529486
TI  - Effect of endoscopic sphincterotomy and interval cholecystectomy on late outcome
      after gallstone pancreatitis.
AB  - BACKGROUND: Endoscopic sphincterotomy alone, or followed by cholecystectomy, are
      options in patients with gallstone pancreatitis. METHODS: Ninety-six patients of
      median age 74 (range 30-93) years with gallstone pancreatitis had endoscopic
      retrograde cholangiography and were followed for a median of 84 (range 33-168)
      months. Forty-eight of 49 patients with, and nine of 47 without, common bile duct
      (CBD) stones had urgent endoscopic sphincterotomy. One patient with, and six
      without, CBD stones had delayed endoscopic sphincterotomy a median of 35 (range
      12-111) days after acute pancreatitis. Thus, 64 patients had endoscopic
      sphincterotomy (group 1) and 32 did not (group 2). Fifteen and 16 patients in
      each group respectively had interval cholecystectomy after a median of 3 months
      and 1 month. RESULTS: Patients in groups 1 and 2 had similar rates of interval
      cholecystectomy (15 of 64 versus 16 of 32 patients respectively) or required
      cholecystectomy (15 of 49 versus five of 16 patients), recurrent CBD calculi
      (three of 64 versus three of 32 patients) or total length of hospitalization
      after interval cholecystectomy (median 15.5 and 15 days) or required (median 22
      and 24 days) cholecystectomy. The overall incidence of recurrent pancreatitis was
      one of 64 patients in group 1 and five of 32 in group 2 (P = 0.02), but after
      interval cholecystectomy the recurrence rate of biliopancreatic symptoms was
      similar (one of 15 patients versus three of 16 patients respectively).
      CONCLUSION: Endoscopic sphincterotomy, but not interval cholecystectomy, reduced
      the overall incidence of recurrent pancreatitis, but not of late biliary
      complications. Some 31 per cent of the patients required cholecystectomy,
      suggesting that routine cholecystectomy should be considered in fit patients
      following acute pancreatitis.

PMID- 9529487
TI  - Genetic alterations in chronic pancreatitis: evidence for early occurrence of p53
      but not K-ras mutations.
AB  - BACKGROUND: In patients suffering from chronic pancreatitis the risk for the
      development of pancreatic cancer ranges from 4 to 6 per cent. Various mutations
      are associated with pancreatic cancer, especially of p53 and K-ras. The incidence
      of these mutations in resected chronic pancreatitic tissue was investigated.
      METHODS: In the present study DNA from 80 samples of tissue from patients with
      chronic pancreatitis was isolated and subjected to single-strand conformation
      polymorphism (SSCP) analysis of p53 exons 5-9 and restriction fragment length
      polymorphism analysis of K-ras (codon 12). RESULTS: No mutations in the K-ras
      gene were detected. On SSCP analysis, eight of 80 cases of chronic pancreatitis
      showed alterations (two in exon 5, four in exon 6, two in exon 7). DNA sequence
      analysis revealed one deletion of 21 amino acids (exon 5), four polymorphisms in
      exon 6 with no change in the amino acid sequence, one point mutation in exon 5,
      and two point mutations located in the intron between exons 6 and 7. CONCLUSION:
      These data show that in some cases of chronic pancreatitis mutations in the p53
      gene occur without morphological evidence of pancreatic cancer.

PMID- 9529488
TI  - Structured data collection improves the diagnosis of acute appendicitis.
AB  - BACKGROUND: Structured preoperative data collection and computer-assisted methods
      are claimed to improve diagnostic accuracy in patients with acute abdominal pain.
      The aim of this study was to evaluate a possible age- and sex-related effect of
      using structured data collection in the preoperative diagnosis of patients with
      suspected acute appendicitis. METHODS: Between 1989 and 1994, clinical and
      demographic data from 1764 consecutive patients were recorded. In 1990 and 1992,
      various detailed symptom, clinical and laboratory data were collected
      prospectively on a structured registration form. Age- and sex-specific diagnostic
      accuracy as well as perforation rate were calculated for each year. RESULTS:
      Diagnostic accuracy increased significantly by 5 (95 per cent confidence interval
      (c.i.) 1-9) per cent when structured data registration was applied. In female
      patients aged between 13 and 40 years, diagnostic accuracy increased by 16 (95
      per cent c.i. 8-24) per cent. Significant changes in diagnostic accuracy were not
      seen in other subgroups. Perforation rates remained unchanged during the entire
      study period. CONCLUSION: In this population-based study, diagnostic accuracy in
      patients operated on for suspected acute appendicitis increased for all patients
      when structured preoperative data collection was used. However, the only subgroup
      with a significant increase in diagnostic accuracy was female patients aged
      between 13 and 40 years. Perforation rate was unaffected by structured data
      collection.

PMID- 9529489
TI  - How to secure the cystic duct at laparoscopic cholecystectomy.

PMID- 9529490
TI  - Comparison of computed tomography and duplex imaging in assessing aortic
      morphology following endovascular aneurysm repair.
AB  - BACKGROUND: Computed tomography (CT) has been used to assess patients following
      endovascular aneurysm repair to determine the need for secondary endoluminal or
      operative procedures. This prospective study compared CT and duplex imaging to
      evaluate aneurysm morphology following endoluminal aortic grafting. METHODS:
      Twenty patients were evaluated at regular intervals following successful
      endoluminal aneurysm repair. CT and duplex scanning were compared in their
      ability to determine aneurysm and aortic diameter, the presence of perigraft
      extravasation (endoleaks) and technical defects in the endograft. RESULTS: In 20
      patients who were assessed 6 months after operation, duplex imaging identified
      four endoleaks (two early, two late; one proximal, three distal). In three cases,
      the aneurysm diameter progressively increased after operation. In patients with a
      thrombosed aneurysm sac, the aneurysm regressed at a median of 0.40 (range 0.13
      0.8) cm per year. The CT findings were similar (median regression 0.43 (range 0
      1.0) cm per year), although CT was unable to predict the site of the leak as
      accurately as duplex imaging. CT demonstrated that the diameter of the juxtarenal
      aorta increased following endografting. CONCLUSION: Duplex imaging is a less
      invasive, less costly alternative to CT in the follow-up of patients after
      endoluminal aortic surgery. Increase in size of the aneurysm sac following
      endovascular aneurysm repair strongly suggests the presence of an endoleak.

PMID- 9529491
TI  - Influence of graft material on blood rheology and plasma biochemistry following
      insertion of an infrainguinal bypass graft.
AB  - BACKGROUND: Occlusive arterial disease causes alterations in blood rheology and
      levels of potential thrombotic and fibrinolytic mediators. The aim of this study
      was to investigate the effect of graft materials on these parameters in patients
      undergoing successful infrainguinal revascularization. METHODS: Some 186
      consecutive infrainguinal grafts were observed for 12 months. Venous blood was
      sampled before operation and at 3, 6, and 12 months after surgery. Samples were
      assayed for thrombotic and rheological parameters. An area under the curve
      analysis was used to compare the effects of vein and synthetic grafting on these
      parameters in 99 patients whose grafts remained patent and free from stenosis.
      RESULTS: Plasma levels of fibrin degradation products were significantly higher
      in patients with synthetic grafts (n = 46) than in those with autogenous vein
      grafts (n = 53) (median 274 versus 150 ng/ml; P < 0.001). There were no
      significant differences in plasma fibrinogen or any other parameters between the
      two groups. CONCLUSION: Patients with a synthetic infrainguinal graft have a
      higher fibrin turnover than those with a vein graft. Further studies are required
      to determine whether this increase in fibrin turnover is an essential requirement
      to maintain patency of a synthetic infrainguinal graft.

PMID- 9529492
TI  - Risk factors for anastomotic leakage after resection of rectal cancer.
AB  - BACKGROUND: The most important surgical complication following rectal resection
      with anastomosis is symptomatic anastomotic leakage, which is associated with a 6
      22 per cent mortality rate. The aim of this retrospective study was to evaluate
      the risk factors for clinical anastomotic leakage after anterior resection for
      cancer of the rectum. METHODS: From 1980 to 1995, 272 consecutive anterior
      resections for rectal cancer were performed by the same surgical team; 131
      anastomoses were situated 5 cm or less from the anal verge. The associations
      between clinical anastomotic leakage and 19 patient-, tumour-, surgical-, and
      treatment-related variables were studied by univariate and multivariate analysis.
      RESULTS: The rate of clinical anastomotic leakage was 12 per cent (32 of 272).
      Multivariate analysis of the overall population showed that only male sex and
      level of anastomosis were independent factors for development of anastomotic
      leakage. The risk of leakage was 6.5 times higher for anastomoses situated less
      than 5 cm from the anal verge than for those situated above 5 cm; it was 2.7
      times higher for men than for women. In a second analysis of low anastomoses (5
      cm or less from the anal verge; n = 131), obesity was statistically associated
      with leakage. CONCLUSION: A protective stoma is suitable after sphincter-saving
      resection for rectal cancer for anastomoses situated at or less than 5 cm from
      the anal verge, particularly for men and obese patients.

PMID- 9529493
TI  - Vaginal endosonography of the anal sphincter complex is important in the
      assessment of faecal incontinence and perianal sepsis.
AB  - BACKGROUND: Anal endosonography is an established technique in the evaluation of
      anorectal disease. However, it is sometimes difficult to visualize the anterior
      part of the sphincter complex and anal endosonography may be impossible when anal
      pain or stenosis is present. The aim of this study was to evaluate vaginal
      endosonography in the diagnosis of faecal incontinence and perianal sepsis.
      METHODS: Anal and vaginal endosonography were performed in 56 women with faecal
      incontinence (n = 36) or perianal sepsis (n = 20). The technique and pelvic floor
      anatomy were described, anal sphincter measurements with anal and vaginal
      endosonography were compared, and the additive value of vaginal over anal
      endosonography in the diagnosis of faecal incontinence and perianal sepsis was
      assessed. RESULTS: The pelvic floor was clearly imaged with vaginal
      endosonography. However, after a relatively short learning curve it was still not
      possible to image the anal sphincters in three of 28 patients. Except for
      external anal sphincter thickness, which was significantly lower, all anal canal
      structure measurements were greater with vaginal than with anal endosonography.
      Concerning the diagnosis of either faecal incontinence or perianal sepsis,
      vaginal endosonography added important information in comparison with anal
      endosonography in 14 (25 per cent) of 56 patients. CONCLUSION: Vaginal
      endosonography provides reliable images of the anal sphincters in an undistorted
      fashion, thereby increasing the diagnostic yield of faecal incontinence and
      perianal sepsis in 25 per cent of patients. Therefore, endosonographists should
      become acquainted with this technique.

PMID- 9529494
TI  - Management of symptomatic locoregional recurrence during regional chemotherapy
      for colorectal liver metastases.
AB  - BACKGROUND: The incidence of symptomatic locoregional recurrence is doubled in
      patients receiving regional chemotherapy with hepatic arterial floxuridine
      infusion (HAI) compared with that in those with colorectal liver metastases
      treated by symptom control. This study assessed the management of symptomatic
      locoregional recurrence in HAI-treated patients with colorectal liver metastases.
      METHODS: A retrospective review of all patients with colorectal liver metastases
      treated by HAI in one hospital over a 10-year period was carried out and the
      management of those who developed symptomatic locoregional recurrence was
      studied. RESULTS: Twenty-three (14 per cent) of 166 HAI-treated patients with
      colorectal liver metastases developed symptoms of locoregional recurrence. Liver
      metastases were responding to HAI at the onset of symptoms in 19 (ten abdominal,
      nine pelvic recurrence) of the 23 patients. Resection of abdominal recurrence was
      possible in seven of the ten patients, with a median hospital stay of 14 days;
      there was one perioperative death. Resected patients survived a median of 15
      months after resection of the recurrence, with five of seven remaining free of
      symptoms of locoregional recurrence. In contrast, six of nine HAI-responding
      patients with pelvic recurrence treated by external beam radiotherapy died from
      uncontrolled symptomatic pelvic disease. CONCLUSION: Resection of abdominal
      recurrence achieved worthwhile palliation in patients with HAI-controlled liver
      metastases, but palliation of pelvic recurrence by irradiation was
      unsatisfactory.

PMID- 9529495
TI  - Intra-abdominal and pelvic abscess in Crohn's disease: results of noninvasive and
      surgical management.
AB  - BACKGROUND: Intra-abdominal and pelvic abscesses occur in 10-30 per cent of
      patients with Crohn's disease. The aim of this study was to establish the
      clinical characteristics and outcome of patients admitted over a 4-year period
      with an abdominal or pelvic abscess secondary to Crohn's disease. METHODS:
      Patients with Crohn's disease-related intra-abdominal or pelvic abscess were
      identified from a prospectively collected database, comprising all admissions
      between 1991 and 1994. Medical records were reviewed retrospectively and data
      gathered regarding management and outcome. RESULTS: Thirty-six patients were
      identified with Crohn's disease-related abscess, of whom 15 were considered for
      initial percutaneous drainage. Drainage was technically possible in eight of
      these patients: it failed in four, gave good long-term results in two, and was
      followed by recurrence after 3 years in one and by later surgery unrelated to the
      abscess in one. Twenty-eight patients underwent surgery, with only four requiring
      a stoma. Complications occurred in 12 patients. At 3 months, 22 of the 36
      patients were in remission. CONCLUSION: Crohn's intra-abdominal abscesses are
      associated with a high morbidity rate. Selected cases can be drained
      percutaneously, without adding to the morbidity, and sometimes resulting in
      abscess resolution.

PMID- 9529496
TI  - Surgical resection of locally recurrent colorectal adenocarcinoma.
AB  - BACKGROUND: Recurrence rates after curative resection of colorectal
      adenocarcinoma remain steady at 50 per cent. Thirty per cent of the deaths are
      linked to locoregional recurrence. The aim of this study was to evaluate the
      results of resection for locoregional recurrence. METHODS: This retrospective
      review analyzed a series of 120 patients who underwent resection of colonic (56)
      or rectal (64) locoregional recurrence. Sixty-nine resections were considered as
      curative. Sixty-one recurrences required extended resection. There were nine
      synchronous hepatic resections. RESULTS: The hospital mortality rate was 7 per
      cent and the morbidity rate was 40 per cent. The overall 5-year survival rate was
      27 per cent. Survival was significantly higher: (1) after curative resection (44
      versus 0 per cent after palliative resection, P < 0.0001); (2) in women (44
      versus 11 per cent for men, P = 0.0036); and (3) after resection for intramural
      recurrence (45 versus 19 per cent for extramural recurrence, P = 0.0024).
      Multifactorial analysis showed that curability of the resection was the most
      important prognostic parameter. CONCLUSION: The results in this highly selected
      group seem to justify an attempt at reresection whenever possible. Long-term
      results may be improved by using adjuvant treatment.

PMID- 9529497
TI  - Stapled haemorrhoidectomy: a feasible day-case procedure.

PMID- 9529498
TI  - TRISS methodology in trauma: the need for alternatives.
AB  - BACKGROUND: Trauma and Injury Severity Score (TRISS) methodology has become a
      standard tool for evaluating the performance of trauma centres and identifying
      cases for critical review. Recent work has identified several limitations and
      questioned the validity of the methodology in certain types of trauma. METHODS:
      The usefulness and limitations of the TRISS methodology were evaluated in an
      urban trauma centre. Trauma registry data of 5445 patients with major trauma were
      analysed with respect to 30 demographic, prehospital, injury severity and
      hospitalization attributes. The performance of TRISS was measured primarily by
      the percentage of misclassifications, including false positives and false
      negatives, comparing the survival status predicted by TRISS with the true status.
      Sensitivity, specificity, and positive and negative predictive values were also
      measured for subgroups defined by the 30 attributes. Logistic regression analysis
      was used to identify significant independent factors related to the performance
      of TRISS. RESULTS: The overall misclassification rate was 4.3 per cent. However,
      in many subgroups of patients with severe trauma the misclassification rate was
      very high: 34 per cent in patients older than 54 years with Injury Severity Score
      (ISS) greater than 20; 29 per cent in those with fall injuries and ISS above 20;
      29 per cent in patients with injuries involving four or more body areas and ISS
      greater than 20; 28.6 per cent in patients with injuries needing admission to the
      intensive care unit (ICU) and ISS greater than 20; 26.4 per cent in patients in
      severe distress before reaching hospital with ISS greater than 20; and 26.1 per
      cent in patients whose ISS score was above 20 and who had complications in
      hospital. CONCLUSION: The TRISS methodology has major limitations in many
      subgroups of patients, especially in severe trauma. In its present form TRISS has
      no useful role in major urban trauma centres. Its use should be seriously
      reconsidered, if not abandoned.

PMID- 9529499
TI  - Continuous antibiotic treatment for experimental abdominal sepsis: effects on
      organ inflammatory cytokine expression and neutrophil sequestration.
AB  - BACKGROUND: Tumour necrosis factor (TNF) alpha and interleukin (IL) 1 beta are
      produced in the lung after peritonitis and may contribute to neutrophil-mediated
      organ injury. It was hypothesized that, during experimental peritonitis,
      continuous rather than intermittent antibiotic therapy would reduce lung
      expression of TNF-alpha and IL-1 beta messenger RNA (mRNA) and neutrophil
      sequestration. METHODS: After caecal ligation and puncture, mice received either
      intermittent or continuous cefoxitin, or continuous metronidazole or aztreonam.
      Cytokine mRNAs were determined by reverse transcription differential polymerase
      chain reaction and lung neutrophil content by myeloperoxidase (MPO) assay.
      RESULTS: Continuous cefoxitin reduced median (interquartile range (i.q.r.)) lung
      IL-1 beta mRNA expression ((ratio to beta-actin): continuous 0.18 (0.14-0.34),
      intermittent 0.46 (0.44-0.49), saline 0.43 (0.38-0.53), P < 0.05) and median
      (i.q.r.) lung MPO content (continuous 22.5 (9.7-40), intermittent 65 (57.5-76),
      saline 47 (41-64), P < 0.05) compared with intermittent therapy and saline
      controls. Continuous infusion was also associated with reduced bacteraemia (P <
      0.05) but not serum TNF-alpha or endotoxin levels. Both continuous metronidazole
      and aztreonam reduced lung MPO concentration (P < 0.05) and TNF-alpha and IL-1
      beta mRNA expression (P < 0.05) compared with those in saline controls. These
      effects were dependent on a reduction in the number of susceptible bacteria
      rather than serum TNF-alpha or endotoxin levels. CONCLUSION: The stimulus for
      organ inflammatory cytokine production and neutrophil sequestration during
      peritonitis is the level of bacteraemia present, which is more effectively
      controlled with continuous antibiotic therapy.

PMID- 9529500
TI  - Infiltrating lobular carcinoma of the breast detected by screening.
AB  - BACKGROUND: This study was a retrospective analysis of all patients with invasive
      lobular breast cancer who presented to the University Hospital Nijmegen between
      1980 and 1990, with follow-up to December 1992. A comparison was made between the
      invasive lobular carcinomas detected by breast cancer screening and those
      detected outside the screening project. METHODS: The total number of patients
      with breast cancer during this interval was 937, of whom 136 (14.5 per cent) had
      pure infiltrating lobular carcinoma (ILC). Breast cancer screening identified a
      total of 158 patients with infiltrating breast carcinoma of whom 20 (12.7 per
      cent) had ILC. Outside the screening programme a total of 116 patients with ILC
      were diagnosed during the same interval. RESULTS: The 2- and 5- and 10-year
      disease-free survival rate in the screen-detected group was 100, 100 and 89 per
      cent respectively. For the group outside the screening programme this was 88.4,
      74.3 and 72.5 per cent respectively (P = 0.04). No patient in the screen-detected
      group died from breast cancer during follow-up, whereas the 2- and 5- and 10-year
      breast cancer survival rate for the group detected outside the screening
      programme was 96.5, 89.1 and 70.6 per cent respectively (P = 0.06). CONCLUSION:
      Between 10 and 15 per cent of patients with invasive lobular breast cancer can be
      detected by breast screening. These patients have a favourable outcome compared
      with those who have ILC detected outside the screening programme.

PMID- 9529501
TI  - Anatomical variants during axillary dissection.
AB  - BACKGROUND: This study was done to document the variations encountered in the
      anatomy of the axilla because of the difficulty they can cause during dissection.
      METHODS: A record was made of the anatomy of the axilla in 100 patients with
      breast cancer who had an axillary dissection. RESULTS: The variants from the
      described normal included double axillary veins, abnormal bands of muscle from
      the latissimus dorsi stretching across the axilla and a medial lying
      thoracodorsal nerve. CONCLUSION: Damage to important structures in the axilla
      during axillary dissection can be minimized with an awareness of the possible
      anatomical variations.

PMID- 9529502
TI  - Abdominal lymphangioma in adults and children.
AB  - BACKGROUND: Abdominal lymphangioma is a rare tumour usually classified with
      mesenteric and retroperitoneal cysts. This experience of abdominal lymphangiomas
      contrasts the differences between tumours in children and adults. METHODS:
      Between 1970 and 1996, six patients had surgical resection of an abdominal
      lymphangioma. RESULTS: There were three children aged 4 years or less and three
      adults aged 36-76 years. Two children presented with an acute abdomen and one
      with a rapidly enlarging abdominal girth. Lymphangiomas were located in the
      mesentery and gastrointestinal tract. In adults, symptoms lasted from months to
      years and lymphangiomas were found in the pancreas, spleen and retroperitoneum.
      CONCLUSION: In this series, abdominal lymphangioma presented more acutely in
      children and usually involved the mesentery, whereas in adults the history was
      longer and the tumour was found in the retroperitoneum.

PMID- 9529503
TI  - Reconstruction after total gastrectomy by the interposition of a double jejunal
      pouch using a double stapling technique.
AB  - BACKGROUND: After total gastrectomy, sustaining good nutrition is extremely
      important for maintaining quality of life. A technique of neogastric pouch
      formation based on current physiological reconstructive principles is presented.
      METHODS: The use of a modified interpositioned double jejunal pouch following
      total gastrectomy in 18 patients with cancer was reviewed. This technique results
      in a complete pouch and uses a double stapling technique with site-specific
      anastomosis between the oesophagus and pouch, in which a Hisoid angle is created.
      RESULTS: There were no anastomotic leaks and pouch blood flow was within normal
      expected limits. Mean oesophageal pH above 7.0 for one 24-h period was 7.7 per
      cent. Emptying half-time was 67.8 min. After 2 years mean body-weight was 98.3
      per cent of expected, mean food volume was 94.0 per cent of expected and mean
      meal frequency was 3.0 per day. CONCLUSION: This form of gastric reconstruction
      is an acceptable procedure which improves the quality of life in patients
      undergoing total gastrectomy.

PMID- 9529504
TI  - Tracheobronchial lesions following oesophagectomy: prevalence, predisposing
      factors and outcome.
AB  - BACKGROUND: Lesions of the trachea or main-stem bronchi with air leakage are a
      grave complication of oesophagectomy. METHODS: Prevalence, predisposing factors
      and outcome of non-malignant lesions of the trachea or main-stem bronchi were
      analysed retrospectively in a consecutive series of 785 patients who had
      oesophagectomy for oesophageal cancer. RESULTS: Overall 31 of 785 patients
      developed a tracheobronchial fistula 1-30 days after oesophagectomy. Based on the
      location of the lesions and clinical circumstances, the tracheobronchial fistulas
      were thought to be due to surgical injury (four patients), cuff pressure of the
      tracheostomy tube (two), local peritracheal infection resulting from a cervical
      anastomotic leak (seven) or 'ischaemia' after extensive peritracheal dissection
      (18). On multivariate analysis, transthoracic en bloc resection (P < 0.01) and
      preoperative radiochemotherapy for locally advanced tumours located at or above
      the level of the tracheal bifurcation (P < 0.01) predisposed to this
      complication. CONCLUSION: Non-malignant tracheobronchial lesions are a serious
      complication of transthoracic oesophagectomy with extensive lymph node
      dissection, particularly in patients undergoing preoperative radiochemotherapy
      for locally advanced tumours.

PMID- 9529505
TI  - Cholangitis in malignant biliary obstruction.

PMID- 9529506
TI  - Screening for gastric cancer by Helicobacter pylori serology: a retrospective
      study.
AB  - BACKGROUND: Screening by serology for Helicobacter pylori in young dyspeptic
      patients has been shown to be effective in reducing demand for endoscopy. H.
      pylori has been implicated in the causation of gastric cancer and the reported
      seropositivity rate in patients with gastric cancer ranges from 69 to 94 per
      cent. The aim of this study was to assess the potential value of Helicobacter
      antibodies as a method of selecting dyspeptic patients over the age of 45 years
      for endoscopy. METHODS: A retrospective comparison of the antibody status to H.
      pylori was made between 154 patients with gastric cancer and a sex- and date of
      birth-matched dyspeptic control group. Results from the former group were
      correlated with demographic data and tumour characteristics. RESULTS:
      Significantly more patients with gastric cancer were seropositive than controls
      (77 versus 66 per cent). H. pylori was not related to the Lauren classification
      of the tumour. Tumour site was significant: body and antrum tumours were
      associated with Helicobacter whereas cardial tumours appeared to be unrelated.
      CONCLUSION: Screening by antibody assays to H. pylori would miss more than 30 per
      cent of current gastric cancers. The increasing incidence of cardial cancer would
      cause this percentage to rise in the future.

PMID- 9529507
TI  - Bacterial translocation in multiple organ failure: cause or epiphenomenon still
      unproven.

PMID- 9529508
TI  - Long-term oral administration of branched chain amino acids after curative
      resection of hepatocellular carcinoma: a prospective randomized trial.

PMID- 9529509
TI  - Statistical commentary.

PMID- 9529510
TI  - Hand-held Doppler as a screening test in primary varicose veins.

PMID- 9529511
TI  - Hand-held Doppler as a screening test in primary varicose veins.

PMID- 9529512
TI  - Low mortality following resection for pancreatic and periampullary tumours in
      1026 patients: UK survey of specialist pancreatic units.

PMID- 9529513
TI  - Low mortality following resection for pancreatic and periampullary tumours in
      1026 patients: UK survey of specialist pancreatic units.

PMID- 9529514
TI  - Low mortality following resection for pancreatic and periampullary tumours in
      1026 patients: UK survey of specialist pancreatic units.

PMID- 9529515
TI  - Low mortality following resection for pancreatic and periampullary tumours in
      1026 patients: UK survey of specialist pancreatic units.

PMID- 9529516
TI  - Raloxifene for postmenopausal osteoporosis.

PMID- 9529517
TI  - Trovafloxacin.

PMID- 9529518
TI  - Sibutramine for obesity.

PMID- 9529519
TI  - COP1b, an isoform of COP1 generated by alternative splicing, has a negative
      effect on COP1 function in regulating light-dependent seedling development in
      Arabidopsis.
AB  - COP1 is a negative regulator of Arabidopsis light-dependent development. Mutation
      of the COP1 locus causes constitutive photomorphogenesis in the dark. Here, we
      report the identification of an isoform of the COP1 protein, named COP1b, which
      is generated by alternative splicing. COP1b has a 60-amino acid deletion in the
      WD-40 repeat domain relative to the full-length COP1. This splicing step is light
      independent and takes place mostly in mature seeds and in germinating seedlings.
      Transgenic Arabidopsis plants that overexpress COP1b show a de-etiolated
      phenotype in the dark, with a short hypocotyl, open and developed cotyledons. The
      transgenic seedlings are adult-lethal. These phenotypes closely resemble that of
      severe cop-1 mutants, indicating that COP1b has a dominant negative effect on
      COP1 function.

PMID- 9529520
TI  - Autoregulation of the partition genes of the mini-F plasmid and the intracellular
      localization of their products in Escherichia coli.
AB  - The sopAB operon and the sopC sequence, which acts as a centromere, are essential
      for stable maintenance of the mini-F plasmid. Immunoprecipitation experiments
      with purified SopA and SopB proteins have demonstrated that these proteins
      interact in vitro. Expression studies using the lacZ gene as a reporter revealed
      that the sopAB operon is repressed by the cooperative action of SopA and SopB.
      Using immunofluorescence microscopy, we found discrete fluorescent foci of SopA
      and SopB in cells that produce both SopA and SopB in the presence of the sopC DNA
      segment, but not in the absence of sopC, suggesting the SopA-SopB complex binds
      to sopC segments. SopA was exclusively found to colocalize with nucleoids in
      cells that produced only SopA, while, in the absence of SopA, SopB was
      distributed in the cytosolic spaces.

PMID- 9529522
TI  - Expression of a chromosomally integrated, single-copy GFP gene in Candida
      albicans, and its use as a reporter of gene regulation.
AB  - Genetically engineered versions of the GFP gene, which encodes the green
      fluorescent protein of Aequorea victoria, were placed under the control of the
      constitutively active Candida albicans ACT1 promoter and integrated in single
      copy into the genome of this pathogenic yeast. Integrative transformants in which
      one of the two ACT1 alleles had been replaced by a GFP gene exhibited a
      homogeneous, constitutive fluorescent phenotype. Cells expressing GFP with the
      wild-type chromophore exhibited very weak fluorescence compared to those GFP
      proteins with the S65T or S65A, V68L, S72A (GFPmut2) chromophore mutations.
      Substitution of the CTG codon, which specifies serine instead of leucine in C.
      albicans, by TTG was absolutely necessary for GFP expression. Although GFP mRNA
      levels in cells containing a GFP gene with the CTG codon were comparable to those
      of transformants containing GFP with the TTG substitution, only the latter
      produced GFP protein, as detected by Western blotting, suggesting that the
      frequent failure to express heterologous genes in C. albicans is principally due
      to the noncanonical codon usage. Transformants expressing the modified GFP gene
      from the promoter of the SAP2 gene, which encodes one of the secreted acid
      proteinases of C. albicans, showed fluorescence only under conditions which
      promote proteinase expression, thereby demonstrating the utility of stable,
      chromosomally integrated GFP reporter genes for the study of gene activation in
      C. albicans.

PMID- 9529521
TI  - The Aspergillus nidulans CCAAT-binding factor AnCP/AnCF is a heteromeric protein
      analogous to the HAP complex of Saccharomyces cerevisiae.
AB  - The Aspergillus nidulans hapC gene was expressed as a fusion protein with MalE or
      glutathione-S-transferase (GST) in Escherichia coli, and used for the
      purification of HapC and the preparation of anti-HapC antiserum. The CCAAT
      binding factor AnCP/AnCF contains a component with an approximate molecular mass
      of 32 kDa that cross-reacts with the antibody. The MalE-HapC fusion protein was
      able to replace authentic HapC in AnCP when incubated under appropriate
      conditions. Furthermore, reconstitution experiments with recombinant HapC, yHAP2
      and yHAP5 polypeptides showed that all three polypeptides were required for the
      assembly of a complex capable of binding to CCAAT-containing taaG2 promoter DNA.
      The relationship between AnCP/AnCF and the Saccharomyces cerevisiae HAP complex
      is discussed.

PMID- 9529523
TI  - Characterization of the gene cluster for biosynthesis of macrocyclic
      trichothecenes in Myrothecium roridum.
AB  - Macrocyclic trichothecenes are toxic sesquiterpenoids that are produced by
      certain fungi and plants. The unique structural features of macrocyclic
      trichothecenes result in increased toxicity relative to other trichothecene
      structural types. Here we report the sequences and relative locations of the
      MRTRI5, MRTRI6, and MRTRI4 genes in the biosynthetic pathway for macrocyclic
      trichothecenes in Myrothecium roridum. The deduced sequences of the products of
      MRTRI5 and MRTRI4 display overall identities of 75 and 63%, respectively, with
      the corresponding proteins in Fusarium sporotrichioides. Based on sequence
      comparisons, MRTRI5 encodes the enzyme trichodiene synthase, which has been shown
      to catalyze the first step in the trichothecene pathways of Fusarium and
      Trichothecium species. MRTRI6 encodes a transcription factor (392 amino acids)
      required for pathway gene expression, and the predicted MRTRI4 product (533 amino
      acids) is a cytochrome P450 monooxygenase responsible for the initial oxygenation
      step in the pathway. The sizes of the predicted products of MRTRI5 and MRTRI4
      show good agreement with their apparent counterparts in the Fusarium pathway;
      however, the protein specified by MRTRI6 is almost twice the size of its putative
      homolog in F. sporotrichioides. Only the C-terminal 124 residues of MRTRI6,
      containing the proposed Cys2His2 zinc finger motifs, show significant similarity
      (65% identity) to the TRI6 sequence in F. sporotrichioides. MRTRI4 can
      successfully complement a TRI4-mutant in F. sporotrichioides, although the
      resulting trichothecene profile differed from that observed in wild-type strains.
      Complemented mutants accumulated low levels of T-2 toxin, in addition to
      sambucinol, deoxysambucinol, and the pathway intermediates trichothecene and
      isotrichodiol. Mapping data indicate that the genes of the macrocyclic
      trichothecene pathway in M. roridum are clustered, but that their organization
      and orientation differ markedly from those of the trichothecene gene cluster
      found in F. sporotrichioides. These results show that the biosynthetic pathways
      for macrocyclic trichothecenes are closely related to other trichothecene
      pathways and that the evolution of gene clusters for the biosynthesis of natural
      products in fungi can involve significant rearrangements.

PMID- 9529524
TI  - The Sinorhizobium meliloti MucR protein, which is essential for the production of
      high-molecular-weight succinoglycan exopolysaccharide, binds to short DNA regions
      upstream of exoH and exoY.
AB  - Sinorhizobium meliloti (Rhizobium meliloti) is able to produce two different
      exopolysaccharides, succinoglycan and galactoglucan. Mutations in the mucR gene
      of S. meliloti result in the stimulation of galactoglucan synthesis, while the
      type of succinoglycan produced is modified. In culture supernatants of a mucR
      mutant, low-molecular-weight succinoglycan is present, whereas no high-molecular
      weight succinoglycan could be detected. The biosynthesis of succinoglycan is
      directed by the products of the exo gene cluster. Two DNA fragments from this
      cluster, one located in front of the exoH gene and one in the intergenic region
      between the divergently transcribed genes exoX and exoY, were shown to represent
      effective binding sites for MucR. Whereas the latter binding site contains an
      inverted repeat motif, the former does not. However, the binding of MucR did not
      strongly modify the transcription of the exo genes involved. In the mucR mutant
      the expression levels of exoH-lacZ and exoX-lacZ transcriptional fusions were
      found to be increased 1.5- and 1.7-fold, respectively. On the other hand, the
      expression level of an exoY-lacZ transcriptional fusion was found to be 1.5-fold
      lower in the mucR mutant than in the wild-type background. Comparison of the DNA
      sequences of MucR-binding sites provides insight into the structural requirements
      for binding of MucR.

PMID- 9529525
TI  - A genetic screen for elements of the network that regulates neurogenesis in
      Drosophila.
AB  - The development of external sensory organs on the notum of Drosophila is promoted
      by the proneural genes achaete and scute. Their activity defines proneural cell
      clusters in the wing imaginal disc. Ectopic expression, under control of the GAL4
      system, of the proneural gene lethal of scute (l'sc) causes the development of
      ectopic bristles. Persistent ectopic expression of l'sc is not sufficient to
      impose a neural fate on any given cell. This implies that mutual inhibition,
      mediated by the Notch signaling pathway, occurs among the cells of the ectopic
      proneural cluster. Consequently, the dominant, quantifiable phenotype associated
      with ectopic expression of l'sc is modified by mutations in genes known to be
      involved in neurogenesis. This phenotype has been utilized to screen for dominant
      enhancers and suppressors that modify the number of ectopic bristles. In this
      way, about 100,000 progeny of EMS or X-ray-treated flies have been analyzed to
      identify autosomal genes involved in regulation of the neural fate. In addition
      1200 chromosomes carrying lethal P-element insertions were screened for
      modifiers. Besides mutations in genes expected to modify the phenotype, we have
      isolated mutations in six genes not known so far to be involved in neurogenesis.

PMID- 9529526
TI  - Rearrangements at a hobo element inserted into the first intron of the singed
      gene in the unstable sn49 system of Drosophila melanogaster.
AB  - The cytological structure of the X chromosome and the DNA organisation of the
      singed locus were examined in five singed bristle mutants of Drosophila
      melanogaster. These mutants are all derived from the unstable mutant singed-49,
      isolated from a wild population in the Russian Far East in 1975. Rearrangements
      were found at a site within the first intron of the singed gene, where a hobo
      element is inserted in these mutants. One rearrangement, which is associated with
      a strong bristle phenotype, has an inversion between 2D and the location of
      singed at 7D, which separates the singed promoter from the singed coding region.
      Two phenotypically wild-type derivatives have smaller rearrangements within the
      first intron which do not appear to interfere with singed expression. Two
      derivatives with bristle phenotypes have more complex rearrangements, and one of
      them shows a dominant or antimorphic phenotype. DNA blotting and in situ
      hybridisation experiments show that, in addition to these rearrangements at a
      hobo element inserted at singed, other hobo elements in these strains have been
      mobilised. This system is therefore similar to others in which functional hobo
      elements continue to transpose, resulting in elevated rates of mutation and
      chromosome rearrangement.

PMID- 9529527
TI  - Suppressors of the temperature sensitivity of DNA polymerase alpha mutations in
      Saccharomyces cerevisiae.
AB  - We have isolated two high copy, allele-specific suppressors of the temperature
      sensitivity of mutations in POL1, the gene that encodes the catalytic subunit of
      DNA polymerase alpha in the yeast Saccharomyces cerevisiae. Both genes, PSP1 and
      PSP2, also partially suppressed a mutation in POL3 which encodes DNA polymerase
      delta, and both also affected a mutation in CDC6, which acts in initiation of DNA
      replication. Suppression was not general, since ts mutations in several genes
      unrelated to replication were not affected, PSP1 was partially effective on low
      copy-number vectors, while PSP2 required high copy numbers. The presence of
      suppressing plasmids did not alter the steady-state level of Pol1 protein, so
      suppression does not appear to be due to an increase in production or stability
      of Pol1p. Deletion of either PSP gene or both in combination resulted in
      apparently normal viable cells. While neither gene is homologous to genes with
      known functions, PSP1 and PSP2 both have unusual amino acid compositions: PSP1 is
      rich in asparagine and glutamine, while PSP2 is rich in asparagine and contains
      "RGG" motifs that have been associated with RNA-binding proteins. We also
      describe a transposon-mediated strategy that should be generally effective for
      rapid characterization of multicopy suppressors.

PMID- 9529528
TI  - The relation between ppGpp and the PHO regulon in Escherichia coli.
AB  - Starving of Escherichia coli cells for inorganic orthophosphate (Pi) results in
      the accumulation of spoT-dependent ppGpp and induces the expression of genes of
      the PHO regulon. In a delta relA delta spoT strain that is unable to accumulate
      ppGpp the expression of two genes (phoA and pstS) that belong to the PHO regulon
      is impaired, even in constitutive mutants. The transcription of phoA and of pstS
      is not affected in the ppGpp0 strain, and therefore this impairment is due to a
      post-transcriptional defect. Conversely, overexpression of ppGpp inhibits
      transcription of these two PHO regulon genes. In phoB mutants, the accumulation
      of ppGpp during Pi starvation is diminished, suggesting that PhoB or one of the
      PHO products is involved in the control of ppGpp accumulation. We propose that
      the presence of ppGpp in the cell, but not its accumulation as a result of the
      starvation stress, is important for the expression of the PHO genes.

PMID- 9529529
TI  - The Arabidopsis transposable element Tag1 is widely distributed among Arabidopsis
      ecotypes.
AB  - Tag1 is an autonomous transposable element (3.3 kb in length) first identified as
      an insertion in the CHL1 (NRT1) gene of Arabidopsis thaliana. Tag1 has been found
      in the Landsberg erecta ecotype of A. thaliana but not in Columbia or WS. In this
      paper, 41 additional ecotypes were examined for the presence of Tag1. Using an
      internal Tag1 fragment as probe, we found that DNA form 19 of the 41 ecotypes
      strongly hybridized to Tag1. Almost all of the Tag1-containing ecotypes had only
      one or two copies of Tag1 per haploid genome, as determined by Southern blot
      analysis. The only exception, Bf-1 from Bretagny-sur-Orge, France, had four
      copies. Two ecotypes, Di-G and S96, gave identical Southern blot patterns to that
      of Landsberg erecta and were subsequently shown to contain Tag1 at the same two
      positions found in Landsberg erecta (loci designated as Tag1-2 and Tag1-3). Two
      other ecotypes, Ag-0 and Lo-1, had a Tag1 element located at Tag1-2 but not at
      Tag1-3. The distance between these two loci was determined to be 0.37 cM.
      Analysis of DNA from two related species, A. griffithiana and A. pumila, showed
      that both species contain sequences that hybridize to Tag1 and that could be
      amplified with an oligonucleotide specific to the terminal inverted repeats of
      Tag1. These results show that Tag1 and related elements are present, and may be
      useful for insertional mutagenesis, in many A. thaliana ecotypes and several
      Arabidopsis species.

PMID- 9529530
TI  - Cloning, mapping and functional characterization of the hemB gene of Pseudomonas
      aeruginosa, which encodes a magnesium-dependent 5-aminolevulinic acid
      dehydratase.
AB  - During tetrapyrrole biosynthesis 5-aminolevulinic acid dehydratase (ALAD)
      catalyzes the condensation of two molecules of 5-aminolevulinic acid (ALA) to
      form one molecule of the pyrrole derivative porphobilinogen. In Escherichia coli,
      the enzyme is encoded by the gene hemB. The hemB gene was cloned from Pseudomonas
      aeruginosa by functional complementation of an E. coli hemB mutant. An open
      reading frame of 1011 bp encoding a protein of 336 amino acids (M(r) 37,008) was
      identified. The gene was mapped to SpeI fragment G and DpnI fragment G of the P.
      aeruginosa chromosome, corresponding to the 10 to 12 min region of the new map or
      19 to 22 min interval of the old map. The 5' end of the hemB mRNA was determined
      and the -10 and -35 regions of a potential sigma 70-dependent promoter were
      localized. No obvious regulation of the hemB gene by oxygen, nitrate, heme or
      iron was detected. Alignment of the amino acid sequences deduced from hemB
      revealed a potential metal-binding site and indicated that the enzyme is Mg(2+)
      dependent. P. aeruginosa hemB was overexpressed in an E. coli hemB mutant using
      the phage T7 RNA polymerase system and its Mg(2+)-dependent activity was directly
      demonstrated.

PMID- 9529531
TI  - Guanosine tetraphosphate (ppGpp)-mediated inhibition of the activity of the
      bacteriophage lambda pR promoter in Escherichia coli.
AB  - It was previously demonstrated that the activity of bacteriophage lambda promoter
      pR is decreased in wild-type Escherichia coli cells starved for amino acids
      (during the stringent response). Since pR activity is necessary for the
      transcriptional activation of ori lambda, this leads to inhibition of the
      replication of plasmids derived from phage lambda. These results led to the
      proposal that the pR promoter susceptible to control by the stringent response.
      However, subsequent studies demonstrated that this promoter is activated by the
      host dnaA gene product and since the dnaA promoter was reported to be controlled
      by the stringent response, it is possible that the inhibition of pR activity in
      amino acid-starved cells is indirect, and results from the impairment of DnaA
      mediated transcriptional activation. Here we present evidence that pR is
      negatively regulated by ppGpp, even when DnaA protein is provided in excess as
      well as in cells devoid of DnaA function. We have checked that the level of ppGpp
      is increased during prolonged (up to 4 h) starvation for isoleucine in relA+
      cells but not in the relA- mutant. At the same time we observed inhibition of
      lambda plasmid replication during the stringent, but not relaxed, response, even
      when DnaA was overproduced. Finally, we found that the activity of a pR-lacZ
      fusion is inhibited after gratuitously induced overproduction of ppGpp in
      unstarved cells, irrespective of the status of the dnaA gene product. We conclude
      that the activity of the pR promoter is inhibited directly by ppGpp.

PMID- 9529532
TI  - The economics of urologic practice in the twenty-first century.
AB  - Our nation's health care has been undergoing an economic revolution. The practice
      of urology has not escaped. Speculation regarding the economics of urologic
      practice in the twenty-first century must be based on the continuation of policy
      trends begun over the last decade by government and managed care coupled with the
      impact of changes in the science of urology, shifting population demographics,
      and changing social factors. The hallmarks of the years ahead include increased
      physician accountability, expanded use of clinical care guidelines, continued
      relentless penetration of managed care, and reduced reimbursement for surgical
      services.

PMID- 9529533
TI  - Manpower needs in urology in the twenty-first century.
AB  - Physician supply factors are based on a number of variables. These include the
      base supply and retirements, which presently show that around 200 urologists are
      retiring per year. Death rates of both patients and physicians are significant.
      The rate of entry of graduating residents is important. Population changes (which
      certainly will continue to increase in the United States) are important. Needs
      based projections, demand-needs based projections, and benchmarked projections
      are important issues. The immigration of physicians is important. So far, I think
      we have seen little emigration of physicians from the United States. A number of
      confounding variables can have impact and are almost impossible to predict at
      present. These include technology changes, disease patterns, and methods of care
      delivery. The Strategic Planning Committee thought we should aim for a band of
      200 to 250 chief residents finishing one per year. We have already reached the
      250 level. At 200 finishing per year, we would have 2300 fewer urologists in the
      year 2020 than we presently have. AT 225/year, we would have 1700 fewer
      urologists. At 250 (our present level), we will have 1100 fewer than now. These
      8800 urologists would be caring for 60 million more patients, of whom 20 million
      would be Medicare patients. These patients would provide over 500 additional
      patient visits/year/urologist. I hope that I have convinced you that the system
      is correcting and responding to multiple market forces. I predict that urologists
      in practice in 2020 will be busy and that we will not have too many urologists if
      the graduating numbers are kept stable. If they drop much more, we could well
      have too few.

PMID- 9529534
TI  - The future of gene therapy in the treatment of urologic malignancies.
AB  - Gene therapy as a field of academic inquiry and as a medical technology is
      perhaps the inevitable consequence of living in today's technologic age. At its
      essence, gene therapy is merely therapy using molecular information. The
      identification of the pivotal role of DNA in the information systems of life and
      the subsequent emergence of molecular biology and its technologies has led to
      routine use of the genetic code-like software to treat human disease in clinical
      trials.

PMID- 9529535
TI  - Tissue engineering in urologic surgery.
AB  - The use of nonurologic tissues in the genitourinary tract is common (owing to a
      lack of a better alternative) despite the known possible adverse effects.
      Selective cell transplantation is providing a means to engineer genitourinary
      tissues that may be used for reconstruction. This novel technology involves an
      interdisciplinary approach, combining techniques of cell biology and materials
      sciences towards the development of functional tissues or organs. Tissues
      associated with urology, such as clitoral, cavernosal, urethral, vesical,
      ureteral, and renal have been created in the laboratory, with varying degrees of
      function. Cells have also been recently used in patients as bulking agents for
      the treatment of vesicoureteral reflux and urinary incontinence. As the science
      of tissue engineering evolves, one can expect a wider application of this
      technology to the armamentarium of urologic surgery.

PMID- 9529537
TI  - Fetal urinary tract abnormalities. Natural history, pathophysiology, and
      treatment.
AB  - Urologic abnormalities are commonly detected on routine obstetric sonographic
      examinations. The progressive nature and potential reversibility of obstructive
      urologic anomalies have led to interest in in utero treatment of these lesions.
      Over 90% of obstructive urologic lesions do not need treatment until after birth.
      For a select group of patients, antenatal treatment may improve postnatal renal
      and pulmonary function. When indicated, minimally invasive nephroamniotic or
      vesicoamniotic stenting is the preferred method of treatment.

PMID- 9529536
TI  - Organ transplantation in the twenty-first century.
AB  - Major advances in the understanding of the immunologic process responsible for
      organ or cellular transplant rejection, a dramatic improvement in available
      immunosuppressive drugs, development of more sophisticated surgical techniques,
      and important progress in posttransplant intensive care over the last 30 years
      have led to a remarkable improvement in success following organ transplantation.
      Whereas excellent short-term survival of most transplanted organs is readily
      achieved, graft loss because of chronic rejection and the worsening problem of
      organ donor shortage remain major concerns in the field of transplantation.
      Recent advances in immunosuppressive drugs, induction of immunologic tolerance,
      and gene therapy strategies may help to prolong organ allograft survival in the
      future. Revised criteria for organ donation and xenotransplantation may one day
      solve the problem of organ supply. Today, as we approach the next millennium, we
      are optimistic that the elusive goal of immunologic tolerance will be achieved
      and perhaps applied to animal tissue. Such will certainly be the challenge for
      the next century.

PMID- 9529538
TI  - Robotic surgery in urology.
AB  - The demand for improved surgical performance and reduced health care costs have
      led to the evaluation of surgical robotic systems. Robotic devices to assist
      urologists with transurethral resection of the prostate, percutaneous renal
      access, and laparoscopy are currently in development or are already in clinical
      use. The rapid advances made in telecommunication technology also have allowed
      for the development of telesurgical systems that permit surgeons to participate
      in surgery from a remote location. In the twenty-first century, surgical robots
      will be efficient, invaluable, and safe adjuncts to urologic practice.

PMID- 9529540
TI  - Laparoscopic surgery. Transition to the future.
AB  - The twenty-first century will usher in a fundamentally new approach to the
      practice of medicine. It will be based heavily on information technologies,
      broadly defined as the devices that acquire information; those that process,
      transmit, and distribute information; and those that use information to provide
      therapy. Although conventional surgery will continue to have a presence, there
      will be radically different surgical approaches and technologies that may become
      the predominant form of surgery. The medical record may become a three
      dimensional visual representation of the individual patient (like the Visible
      Human Project), which can be the vehicle that integrates the entire spectrum of
      health care. Examples of the technologies and infrastructures that support this
      new approach to medicine are discussed and illustrated, with emphasis on how
      technologies improve individual patient care.

PMID- 9529539
TI  - Total alloplastic replacement of the urinary bladder.
AB  - Bladder cancer is the second most common malignancy of the genitourinary tract.
      In 1992, the estimated incidence of bladder cancer in the United States was
      50,000 cases. Cystectomy and urinary diversion were the preferred methods of
      treatment. Currently, these patients undergo various types of intestinal urinary
      diversion. These procedures represent a significant advancement over bilateral
      ureterostomies; however, many problems are associated with their use and they are
      among the topics discussed in this article.

PMID- 9529541
TI  - Three-dimensional computed tomography for planning urologic surgery.

PMID- 9529542
TI  - Open-configuration MR imaging, intervention, and surgery of the urinary tract.
AB  - The open-configuration MR imaging system provides new applications both in
      diagnosis and in therapy of conditions in the urinary tract. In addition to
      conventional imaging, the open configuration permits MR imaging of patients in
      many positions. This has already been shown to be useful in imaging the pelvis
      during voiding, where a sitting position allows urodynamic evaluation. The
      lithotomy position can be used for imaging the prostate, which also permits
      procedural access. The ultimate purpose of the interventional MR imaging suite is
      to integrate therapeutic tools and techniques with MR imaging. From surgical
      planning through specialized imaging systems with minimally invasive surgical
      applications, new methods are being developed and implemented. This new field of
      image-guided therapy will require extensive clinical development and evaluation
      for applications in the urinary tract. This will require a large concentrated
      interdisciplinary effort of surgeons, radiologists, computer scientists,
      engineers, and physicists. Successful integration of basic research and clinical
      work will result in a number of cutting-edge technologies with direct clinical
      application in the urinary tract. Initial projects have included biopsies,
      endoscopies, and real-time procedural control of high-temperature and cryogenic
      ablations. It is anticipated that the current surge in image-guided interventions
      will motivate even more research activity in this field, and will ultimately
      define the role of MR imaging guidance in urologic intervention and surgery.

PMID- 9529543
TI  - Laser tissue welding.
AB  - Laser tissue welding is a technologic innovation that is beginning to move from
      the theoretical laboratory environment to the reality of clinical application.
      This article reviews the concepts, potential advantages, and techniques involved
      in laser tissue welding as they apply to urology.

PMID- 9529544
TI  - Telemedicine. Present applications and future prospects.
AB  - Information technology has enabled much of the business community to function in
      a time and place-independent manner. Health care has lagged in adopting this
      technology because of tradition, concern for patient security and
      confidentiality, liability, and licensure issues. This article reviews the
      current state of telemedicine technology, its applications, and opportunities for
      further development. Urology is identified as a specialty that stands to benefit
      from advances in technologies applicable to remote diagnosis, monitoring and care
      of patients, physician training, and record keeping.

PMID- 9529545
TI  - Endoscopic treatment of vesicoureteral reflux in children.
AB  - Endoscopic surgery for vesicoureteral reflux involves injection of a substance
      beneath the ureterovesical junction (UVJ) to buttress this region. In children,
      this procedure typically is performed under anesthesia on an outpatient basis,
      with minimal postoperative pain and a rapid recovery.

PMID- 9529546
TI  - Reactive eccrine syringofibroadenoma: an emerging subtype.

PMID- 9529547
TI  - Intracutaneous histamine injection can detect damage of cutaneous afferent fibres
      in postherpetic neuralgia.
AB  - BACKGROUND: The axon reflex response in diseased skin of patients with
      postherpetic neuralgia may be significantly impaired. OBJECTIVE: In the present
      study we introduced a simple test for quantifying the decreased axon reflex flare
      response in the clinical routine. METHODS: Histamine was intradermally applied to
      the diseased dermatome as well as to the corresponding dermatome of the
      contralateral side of the body. Ten minutes after application, skin blood flow
      and the extension of the hyperaemic response were assessed by means of laser
      Doppler scanning. RESULTS: In the skin region affected by the postherpetic
      neuralgia, the hyperaemic area was significantly smaller than in the healthy
      skin. The mean flux values did not differ significantly between the two sites.
      There was no correlation between the hyperaemic response and the intensity of
      pain sensation assessed by a clinical visual analogue score. CONCLUSION: The
      smaller hyperaemic area in the dermatome with postherpetic neuralgia strongly
      indicates a C fibre or C nociceptor damage. We consider histamine injections as a
      useful tool in the differential diagnosis of postherpetic neuralgia.

PMID- 9529548
TI  - Thirty hours' evaluation of UVB-induced erythema by chromometry and
      microflowmetry.
AB  - BACKGROUND: Individual UVB photosensitivity is usually investigated by
      determining the minimal erythemal dose (MED). Nevertheless, factors such as room
      light intensity and subjective experience of the observer can influence the
      erythema perception and, therefore, the MED assessment. OBJECTIVE: To evaluate
      the relationship between the clinical and the chromometric and microflowmetric
      analyses of the UVB-induced erythema in 2 healthy volunteers. METHODS: A bank of
      6 fluorescent mercury vapor tubes (Philips TL 12/20 W) was utilized as a source
      of UVB light. Three skin areas (4 cm2), from the dorsal region of each subject,
      were irradiated with 3 different UVB doses corresponding to: (1) MED; (2) 0.7
      MED, and (3) 1.3 MED. RESULTS: (1) both microflowmetric and chromometric
      parameters reached a maximum peak 10-12 h after irradiation and maintained high
      values also 30 h after irradiation; (2) both microflowmetric and chromometric
      values were directly related to the UVB doses; (3) in some cases the
      microflowmetric values started to increase when the chromatic changes were still
      undetectable. CONCLUSION: These preliminary data confirm that the visual
      determination of MED performed 24 h after irradiation is a correct procedure.
      Nevertheless, the microflowmetric may precede the chromatic changes suggesting
      that vasodilatation follows irradiation without a latent period.

PMID- 9529549
TI  - Effect of organic solvents on normal human stratum corneum: evaluation by the
      corneoxenometry bioassay.
AB  - BACKGROUND: Organic solvents alter the stratum corneum structure and barrier
      function. OBJECTIVE: To measure the effect of various solvents upon human stratum
      corneum using the ex vivo corneoxenometry bioassay which is a variant of
      corneosurfametry. METHODS: Corneoxenometry entails collection of human stratum
      corneum by cyanoacrylate. The material is immersed in organic solvents for
      periods ranging from 1 to 120 min. After staining the samples with a toluidine
      blue-basic fuchsin solution, the color is measured using reflectance colorimetry.
      Solvent aggressivity to the stratum corneum correlates with the color darkening
      of the samples. RESULTS: The least aggressive solvent was hexane, followed by
      ethanol, methanol, hexane-ethanol, chloroform, chloroform-methanol and hexane
      methanol. The influence of contact time between solvents and the stratum corneum
      showed a logarithmic pattern which varied according to the solvent. CONCLUSION:
      Data are in line with previous experiments conducted in vivo and in vitro, thus
      indicating the predictive value of corneoxenometry. Such a bioassay may avoid
      hazards of some in vivo human testings.

PMID- 9529550
TI  - Toxocariasis and Wells' syndrome: a causal relationship?
AB  - BACKGROUND: The etiology of Wells' syndrome or eosinophilic cellulitis is
      unknown. Various triggering factors, such as myeloproliferative disorders,
      lymphoma, infections/infestations, insect bites and drugs have been reported. In
      1979, Wells was the first who pointed out some common features of eosinophilic
      cellulitis and skin lesions in toxocariasis. OBJECTIVE: We report 2 patients who
      exhibited the characteristic clinical and histological features of Wells's
      syndrome together with elevated antibody titers to the excretory-secretory
      antigen of Toxocara canis. RESULTS: In both patients, the skin lesions
      disappeared after oral albendazole treatment and no recurrences were observed.
      The clinical response was followed by a normalization of the Toxocara antibody
      titer. In contrast, a patient with eczematoid skin lesions, eosinophilia and an
      elevated Toxocara antibody titer did not benefit from albendazole treatment
      despite serological normalization. CONCLUSION: Taken together, these cases lend
      support to a causal relationship of Toxocara in selected patients with Wells'
      syndrome.

PMID- 9529551
TI  - Occupational contact dermatitis to propacetamol. Allergological and chemical
      investigations in two new cases.
AB  - BACKGROUND AND OBJECTIVE: In 2 new cases of occupational contact dermatitis due
      to a recently described allergen (propacetamol), a prodrug which is a soluble
      diethylglycidyl ester of paracetamol, an allergological investigation was
      performed to elucidate the nature of the allergen involved in the propacetamol
      contact sensitivity. OBSERVATIONS: Two nurses with eczema of the hands and face
      had positive patch tests to Pro-Dafalgan. Every day the nurses prepared
      injections of Pro-Dafalgan (propacetamol dissolved in sodium citrate). The
      sensitization was due to propacetamol and not to the solvent. To elucidate which
      part of propacetamol was responsible for the sensitization, the 2 nurses were
      patch-tested with diethylamine, paracetamol (diluted in different vehicles) and
      some of their chemical analogues and potential impurities which were all
      negative. CONCLUSIONS: Propacetamol induces airborne contact dermatitis with no
      evidence of sensitization to paracetamol or diethylglycine, possibly because of
      either the presence of unknown impurities and/or an antigenic structure related
      to the covalent bond of the prodrug.

PMID- 9529552
TI  - The early phase of epidermal barrier regeneration is faster in patients with
      atopic eczema.
AB  - BACKGROUND: Altered epidermal barrier function as determined by transepidermal
      water loss (TEWL) is a typical feature in patients with atopic eczema (AE).
      OBJECTIVE: The purpose of this study was to assess the kinetics of epidermal
      regeneration after barrier perturbation induced by two different stimuli, namely
      acetone treatment (removal of stratum corneum lipids) and tape stripping (removal
      of the nonviable stratum corneum). METHODS: Fifteen patients with AE and 12
      nonatopic healthy controls were investigated. An area of 9.0 cm2 of clinically
      normal skin of the forearm flexural side was treated by acetone or tape stripping
      in a way that an increase in TEWL of 3.5-4.0 times the pretreatment value was
      achieved. TEWL was recorded directly after perturbation (tO), after 15 min (tl),
      3 h (t2), 6 h (t3), 24 h (t4), 48 h (t5), 72 h (t6) and 96 h (t7). RESULTS: The
      speed of epidermal regeneration was faster after acetone treatment, both in the
      patient and the control groups, with no significant difference between the two.
      However, after tape stripping at points t2, t5 and t6, TEWL values relative to tO
      were significantly lower in atopic skin as compared to normal skin (p < 0.05).
      CONCLUSION: The faster regeneration of barrier function after tape stripping in
      patients with AE may be the result of a persisting mild disturbance of barrier
      function. It may be speculated that repair mechanisms are permanently activated,
      and therefore barrier recovery is faster. However, a complete restoration of the
      epidermal barrier function is not achieved, perhaps because of the decreased
      content of ceramides in atopic skin.

PMID- 9529553
TI  - Co-existence of leukoderma with features of Dowling-Degos disease: reticulate
      acropigmentation of Kitamura spectrum in five unrelated patients.
AB  - BACKGROUND: The spectrum of Dowling-Degos disease-reticulate acropigmentation of
      Kitamura (DDD-RAK) is a group of rare autosomal dominant disorders that have in
      common a unique histological picture of hyperpigmented digitate epidermal
      'downgrowths'. Patients with the DDD-RAK spectrum may show hyperpigmented macules
      and papules, facial pits, breaks in dermatoglyphics and epidermoid cysts.
      OBSERVATIONS: We examined 5 unrelated patients, 3 females and 2 males (age range
      22-35 years), who presented with clinical and histological features of the DDD
      RAK spectrum. In addition, the patients presented with hypo- or depigmented
      macules and papules. Histopathology of the lesions revealed features that were
      identical to DDD-RAK; there were, however, diminution or absence of pigmentation.
      Family histories for pigmented lesions and leukoderma were positive in all
      patients and consistent with autosomal dominant modes of inheritance. CONCLUSION:
      These 5 cases, together with isolated reports in the literature of achromic
      lesions with histological features of DDD-RAK, point to the hypothesis that
      achromic macules and papules may be a feature of the DDD-RAK spectrum.

PMID- 9529554
TI  - Multiple eruptive dermatofibromas in three men with HIV infection.
AB  - BACKGROUND: Multiple eruptive dermatofibromas (MEDF) are rare and their etiology
      is unknown. An association with immunosuppression has led to the speculation that
      they are the result of an abortive immunoreactive process. In the literature,
      there have been 5 isolated case reports of multiple dermatofibromas and human
      immunodeficiency virus (HIV) infection. Three of these cases had other immune
      modulators present (i.e. prednisone, systemic lupus erythematosus, alpha
      interferon, UVB phototherapy). The other 2 cases had disseminated
      mycobacteriosis. OBSERVATIONS: A series of 3 men with HIV infection and MEDF is
      described. In contrast to previous case reports, our patients did not have other
      immune modulators besides HIV infection nor did they have disseminated
      mycobacteriosis. CONCLUSIONS: This series lends support to the speculation that
      MEDF may be associated with immunosuppression. Further study is needed to
      delineate the exact mechanism for this relationship. These patients presented
      within a 4-month period and illustrate the frequency at which MEDF may be seen in
      the HIV-positive population. As clinicians who care for patients with HIV
      infection, it is important to be aware that MEDF may be seen in this
      immunosuppressed population.

PMID- 9529555
TI  - Postoperative interstitial radiotherapy of keloids by iridium 192: a
      retrospective study of 46 treated scars.
AB  - BACKGROUND: Keloids are clinically vexacious scars characterized by a high
      recurrence rate after excision alone (50-100%). Many adjuvant techniques have
      been used with more or less convincing results. OBJECTIVE: The aim of this study
      is to show the efficiency of keloidectomy and postoperative interstitial
      radiotherapy by an iridium 192 wire. METHODS: During a 14-year period, 39
      patients with keloids (46 keloids) were treated by this regimen. Seven patients
      had been previously treated by intralesional corticosteroids, surgery alone or
      postoperative interstitial radiotherapy, without improvement. A dose of 12 Gy (7
      keloids) to 15 Gy (22 keloids) was delivered at a point 2.5 mm from the axis of
      the wire. For 17 keloids the dose schedule was 15 Gy at a point 5 mm to the wire.
      The median follow-up was 7 months. RESULTS: The overall success rate is close to
      63%. A recurrence occurred in 14 cases without relation to the method used, the
      age or the localization of the lesions. There were no side effects observed.
      CONCLUSIONS: Postoperative interstitial radiotherapy represents an effective,
      unconstraining and safe treatment for keloids if the contraindications are
      respected.

PMID- 9529557
TI  - Sequential combined therapy with thalidomide and narrow-band (TL01) UVB in the
      treatment of prurigo nodularis.
AB  - BACKGROUND: Prurigo nodularis (PN) is a chronic disease of which treatment
      choices are limited. Among them, thalidomide and phototherapy have been used with
      satisfactory results. Unfortunately, the possibility of side effects limits their
      use. OBJECTIVE: To evaluate the efficacy of a sequential combined treatment with
      thalidomide and ultraviolet B (UVB) therapy in order to minimize side effects
      and, thus, making possible a long-term treatment. METHODS: A prospective open
      trial combining thalidomide as initial therapy followed by narrow-band UVB (TL01)
      irradiation until complete or almost complete remission of the disease was
      achieved. RESULTS: An excellent response was obtained after an average of 12
      weeks of thalidomide therapy and 32 UVB courses. CONCLUSIONS: Sequential combined
      therapy with thalidomide and narrow-band UVB therapy could improve the management
      of prurigo nodularis with minimal side effects, although it should probably be
      reserved to men and women over 50 years of age.

PMID- 9529556
TI  - Pruritus in HIV-1 disease: therapy with drugs which may modulate the pattern of
      immune dysregulation.
AB  - BACKGROUND: Pruritus in HIV-1+ patients is common and increases with disease
      progression. The causes of pruritus are numerous including xerosis, drug and
      photoeruptions, follicular and papular eruptions as well as infestations and
      infections by a wide range of organisms. One other possible factor contributing
      to pruritus is the pattern of immune dysregulation. With advancing HIV-1 disease
      there is Th1 to Th2 cytokine switching. METHODS: After some positive results with
      prostaglandin inhibitors, we undertook a study in which we randomly placed
      patients on four different forms of therapy for their pruritus. The therapies
      included hydroxyzine with or without doxepin at night, pentoxifylline,
      indomethacin and topical moisturization with medium-strength topical steroids.
      All patients were evaluated for both subjective relief as well as side effects.
      RESULTS: Patients placed on indomethacin obtained relief more consistently and
      more completely. Patients on pentoxifylline had the fewest side effects of all
      oral therapies. Patients on antihistamines with or without doxepin had the
      highest incidence of side effects, although more of these patients reported a
      greater degree of relief than patients on pentoxifylline. All patients on oral
      therapy overall had greater relief than patients using topical steroids.
      CONCLUSION: The systemic therapies which may modulate the pattern of immune
      dysregulation seen in HIV-1 disease may be beneficial in the pruritus seen in
      late-stage patients.

PMID- 9529558
TI  - Effects of topically applied antioxidants in experimentally provoked polymorphous
      light eruption.
AB  - BACKGROUND: Polymorphous light eruption (PLE) is the most common photodermatosis,
      with a prevalence of 10-20% in Western European countries and in the USA. Only
      few preventive measures for PLE exist, while its etiology and pathogenesis are
      still elusive. Recent theories on pathogenesis discuss the possible influence of
      oxidative stress. OBJECTIVE: The presented randomized, placebo-controlled, double
      blind study examines for the first time the protective effect of 3 different
      topically applied antioxidative preparations in experimentally photo-induced PLE.
      METHOD: 30 patients with a history of PLE underwent photoprovocation after having
      had applied 3 different formulations with antioxidants and one formulation with
      the vehicle only to the extensor surface of their upper arms, representing the
      individual site of predilection, twice daily for 1 week prior to and during the
      consecutive week of photoprovocation. The antioxidants used were combinations of
      different concentrations of alpha-glycosylrutin, ferulic acid and tocopheryl
      acetate. RESULTS: Evaluation after the 4th photoprovocation revealed that the
      development and severity of PLE and concomitant pruritus were significantly
      reduced by the application of distinct combinations of antioxidants. CONCLUSION:
      The results offer a new insight into possible pathomechanisms of PLE and suggest
      a new approach for preventive and therapeutic measures.

PMID- 9529559
TI  - Topical immune modulation with dinitrochlorobenzene in HIV disease: a controlled
      trial from Brazil.
AB  - OBJECTIVE: Despite the rapid spread of human immunodeficiency virus (HIV) in the
      developing countries of Africa, Asia and Latin America, accessible and affordable
      antiretroviral therapies have not been developed. Dinitrochlorobenzene (DNCB) is
      an inexpensive contact sensitizing agent that stimulates cell-mediated immunity
      when applied to the skin. We have examined the clinical and immunologic effects
      of topical DNCB therapy in a cohort of indigent patients with HIV disease from
      Brazil. DESIGN AND METHODS: Thirty-five HIV-infected subjects were divided into a
      control group that refused DNCB therapy (6 patients) and a treatment group that
      applied topical DNCB on a weekly basis throughout the study (29 patients).
      Subjects were monitored for adverse clinical events, progression to AIDS and
      changes in body weight. CD4 and CD8 T-cell counts were also monitored in both
      groups. RESULTS: Control and treated patients were evenly matched in terms of
      age, initial clinical status and prior adverse clinical events. The mean follow
      up was 19.7 months for the control group and 17.8 months for the DNCB group.
      Control patients had significantly more adverse clinical events and progression
      to AIDS during the study than the treatment group (p = 0.002 and p = 0.013,
      respectively). There were no deaths in either group. Control patient weights
      decreased over the study period while DNCB patient weights increased (p < 0.001).
      CD4 and CD8 T-cell counts decreased significantly in the control group and
      increased in the DNCB group (p < 0.001 and p = 0.031, respectively). DNCB therapy
      was well tolerated. CONCLUSIONS: Topical DNCB therapy affords a rational,
      effective and inexpensive treatment approach for HIV disease. DNCB should benefit
      patients in developing nations with limited access to health care.

PMID- 9529560
TI  - Human herpesvirus 7 in patients with pityriasis rosea. Electron microscopy
      investigations and polymerase chain reaction in mononuclear cells, plasma and
      skin.
AB  - BACKGROUND: Clinical evidence suggests a viral etiology for pityriasis rosea
      (PR). OBJECTIVE: To evaluate human herpesvirus (HHV)-6 and HHV-7 as candidates
      for the etiology of PR. METHODS: Blood and skin tissue from 12 patients with
      acute PR, and 12 patients with other dermatoses were studied, as well as blood
      samples from 25 healthy persons. Serum interferon (IFN)-alpha and IFN-gamma were
      analyzed by ELISA. Analysis of morphological changes in cocultured peripheral
      blood mononuclear cells (PBMC) and electron microscopy (EM) to identify viral
      particles were performed. Polymerase chain reaction (PCR) with specific primers
      for HHV-6 and HHV-7 DNA sequences was performed on the plasma and PBMC of
      patients and healthy controls and on the skin of patients with PR and other skin
      diseases. RESULTS: PR plasma contained detectable IFN-alpha and IFN-gamma,
      whereas plasma from controls did not. PBMC from PR patients showed ballooning
      cells and syncytia after 7 days in culture whereas PBMC from controls and
      recovered PR patients did not. This cytopathic effect was also documented in a PR
      patient who relapsed and in Sup-T1 cell cultures inoculated with the cell-free
      supernatant from centrifuged cultured PBMC; in this supernatant, herpesvirus,
      virions were detected by EM, PCR identified HHV-7 DNA in PBMC, plasma and skin
      from all patients with active PR and in the PBMC only of 5 patients tested 10-14
      months later. Weaker signals of HHV-7 DNA were detected in PBMC of 11 controls,
      but not in their plasma. Skin was negative for HHV-7 in all control specimens.
      CONCLUSIONS: Although the detection of HHV-7 DNA in PBMC and tissues does not
      prove directly a causal role, HHV-7 DNA in cell-free plasma corresponds to active
      replication which supports a causal relationship. We propose that PR is a
      clinical presentation of HHV-7 reactivation.

PMID- 9529561
TI  - Idiopathic palmoplantar hidradenitis. Report of three cases and literature
      review.
AB  - Idiopathic palmoplantar hidradenitis is a new entity consisting of plantar or
      palmoplantar painful erythematous nodules which affect children in good health.
      The histopathologic study shows a neutrophilic hidradenitis. We report on 3 new
      cases of idiopathic plantar hidradenitis and review the literature.

PMID- 9529562
TI  - Disseminated reticulate hypomelanosis developing during primary biliary
      cirrhosis.
AB  - We report on a 50-year-old woman with disseminated reticulate hypomelanosis
      developing on the limbs and abdomen during primary biliary cirrhosis (PBC).
      Histopathological examination showed vacuolar basal cells, dyskeratosis and large
      multinucleated epidermal cells. Diagnosis of lichen sclerosus et atrophicus and
      autoimmune disease are discussed. The similarity between cutaneous changes in PBC
      and a graft-versus-host reaction is outlined.

PMID- 9529563
TI  - 'Dimpling' is not unique to dermatofibromas.
AB  - The dimpling of the skin with lateral compression or 'Fitzpatrick's sign' is
      considered by many to be pathognomonic for dermatofibromas (DFs). Despite the
      description of this sign in all major textbooks, not all DFs dimple and all that
      dimple are not DFs. Other diagnostic investigations such as the use of
      dermatoscopy may help to confirm the clinical suspicion of DF.

PMID- 9529564
TI  - Agminate and plaque-type blue nevus combined with lentigo, associated with
      follicular cyst and eccrine changes: a variant of speckled lentiginous nevus.
AB  - Agminate and plaque-type blue nevi are rarely described. We report the occurrence
      of such a type of blue nevus associated with eccrine changes and a follicular
      cyst all arising on a macular brown background in a 38-year-old man. The patient
      presented numerous blue papules and a plaque, overlapping a light tan patch
      present since birth, on his left thigh. In addition, within the plaque, 3
      papules, discharging at intervals a serous fluid, were present. Since the lesion
      hardened and enlarged, it was surgically excised. Histologic findings revealed a
      lentigo pattern of the epidermis, corresponding to the light tan macular
      background and a plaque-type blue nevus, and areas of eccrine ductal
      proliferations with a ruptured follicular cyst. The association of agminate and
      plaque-type blue nevus, arising on a light brown patch of lentigo, might
      represent a variant of speckled lentiginous nevus. Eccrine proliferations may be
      reactive in nature or represent a more complex hamartomatous lesion. The
      possibility of malignant transformation and the recent enlargement of the lesion
      caused by the ruptured follicular cyst convinced us to carry out a wide surgical
      excision.

PMID- 9529565
TI  - Cutaneous manifestations of relapsing polychondritis in a patient receiving
      goserelin for carcinoma of the prostate.
AB  - Relapsing polychondritis is a chronic rheumatologic disorder of unknown etiology.
      Cutaneous manifestations occur in nearly half of the patients and often precede
      cartilaginous involvement. We present the case of a man with a history of
      prostatic adenocarcinoma who underwent monthly injections of goserelin (Zoladex),
      an LH-RH analogue. Five months after the beginning of the treatment, he presented
      cutaneous manifestations, which then recurred monthly, after each goserelin
      injection. After goserelin interruption and replacement with another treatment
      (cyproterone acetate), the patient was asymptomatic for 2 months. A cutaneous
      relapse then occurred followed by a typical cartilaginous involvement. In our
      observation, goserelin seems to have triggered the cutaneous manifestations of
      relapsing polychondritis. An hormonal precipitating factor in relapsing
      polychondritis has already been suggested by reports of patients whose disease
      worsened under chorionic gonadotropin treatment or during pregnancy.

PMID- 9529566
TI  - Eccrine syringofibroadenomatosis in two patients with bullous pemphigoid.
AB  - A 67-year-old man and an 84-year-old woman developed palmoplantar erythema
      following resolution of bullous pemphigoid (BP). Clinical manifestations of the
      palmoplantar lesions in these 2 patients ranged from prominent, well-demarcated
      erythematous areas with focal erosions and fissures to mild erythema. On
      histological examination, the palmoplantar erythema in one patient showed thin
      reticular strands of proliferating cells which connected with the epidermis and
      extended into the dermis, interwinding and anastomosing irregularly. The second
      patient showed similar mild changes with duct-like luminal formations. These
      histological findings were consistent with the diagnosis of eccrine
      syringofibroadenoma (ESFA). We speculate that these lesions developed as a result
      of the underlying inflammatory process in BP and conclude that ESFA associated
      with an inflammatory condition should be considered a new category of ESFA.

PMID- 9529567
TI  - Eccrine syringofibroadenoma in a patient with erosive palmoplantar lichen planus.
AB  - We report the case of an 82-year-old woman with a 6-year history of erosive
      palmoplantar lichen planus associated with eccrine syringofibroadenoma (ESFA).
      Examination revealed a well-demarcated patche writish of reticulated whitish
      papular lesions in skin of otherwise normal appearance at the border of erosive
      lichen planus plaques. These lesions had the histological appearance of ESFA. We
      suggest that these lesions are induced by the inflammatory remodelling associated
      with erosive lichen planus and propose to consider ESFA in the context of skin
      tissue remodelling as a new subtype of ESFA.

PMID- 9529568
TI  - Annular atrophic lichen planus and Sneddon's syndrome.
AB  - We report the case of a patient who had 2 rare diseases, annular atrophic lichen
      planus (AALP) and Sneddon's syndrome (SNS). This patient had also digital nodules
      with histological abnormalities suggestive of SNS vasculopathy, which have not
      been reported so far. AALP is the most rare of all varieties of lichen planus
      since this case is the third reported to date. The association of livedo racemosa
      and cerebrovascular disease is the hallmark of SNS, the incidence of which is
      estimated to be 4 cases per year per million inhabitants. In both diseases, an
      abnormal production of elastic-tissue-degrading enzymes or a constitutional
      abnormality of the elastic tissue can be postulated, since SNS is characterized
      by arteriolar changes with deterioration of the internal elastic lamina and AALP
      by destruction of the dermal elastic tissue.

PMID- 9529570
TI  - 'Burrow-trucut'--a method for harvesting scabietic burrows.

PMID- 9529569
TI  - Atrial myxoma syndrome mimicking Ehrmann-Sneddon syndrome.
AB  - Livedo racemosa with cerebrovascular lesions has been described as Ehrmann
      Sneddon syndrome. The etiopathogenetic factors provoking the vascular lesions,
      however, are of high diversity reaching from mechanical to autoimmune causes. We
      present a male patient with typical livedo racemosa, muscle pain and feeling of
      coldness of the forearms. By dermatohistopathology and magnetic resonance
      tomography of the brain, Ehrmann-Sneddon syndrome could be confirmed. At this
      time a chronic streptococcal infection could be diagnosed. Antibiotics,
      anticoagulants and vascularity-supplying therapy improved the clinical and
      subjective symptoms. Six months later, the patient developed dizziness, vision
      disorder, hypesthesia of the right forehead, malaise and weight loss. A further
      diagnostic workup including echocardiography revealed a myxoma of the left
      atrium. This report illustrates the association of Ehrmann-Sneddon syndrome with
      cardiac myxoma and points out that cardiac diagnostic examination should be
      included when dealing with small-vessel involvement of the brain.

PMID- 9529571
TI  - Photosensitivity due to ampiroxicam.

PMID- 9529572
TI  - Dideoxyinosine-associated Ofuji papuloerythroderma in an HIV-infected patient.

PMID- 9529573
TI  - Chemotherapy in HIV-infected patients with Kaposi's sarcoma.

PMID- 9529574
TI  - Punch grafting in lichen sclerosus et atrophicus.

PMID- 9529575
TI  - Resistance to activated protein C in patients with venous leg ulcers.

PMID- 9529576
TI  - Rejection of punch grafts in three cases of herpes-simplex-induced lip
      leucoderma: caution and precaution.

PMID- 9529577
TI  - Brachioradial pruritus--an uncommon photodermatosis presenting in a temperate
      climate.

PMID- 9529578
TI  - IMA and blood transfusion services in India.

PMID- 9529579
TI  - Argyrophilic nucleolar organiser regions (AgNORs) in breast lesions.
AB  - Nucleolar organiser regions (NORs) demonstrated by argyrophilia of NOR-proteins
      are indicator of cellular proliferative activity. The NORs can be identified in
      the nuclei as brown or black dots with silver colloidal staining technique in
      formalin fixed paraffin sections and in cytology smears. Seventy-five cases
      including 45 tissue sections and 30 fine needle aspiration cytology (FNAC) smears
      of benign and malignant lesions of breast have been studied to evaluate the
      significance and practical application of AgNOR count per nucleus. Out of 45
      tissue sections 15 belonged to fibrocystic disease, 10 fibro-adenomas and 20
      carcinomas and of the 30 FNAC smears, 10 were fibrocystic disease, 8 fibro
      adenomas and 12 carcinomas. In fibrocystic disease the mean AgNOR count was 1.60
      (FNAC group-0.75, tissue section-1.61). In fibro-adenomas it was 1.61 (FNAC-1.63,
      tissue section-1.59). The mean count in carcinoma was 12.10 (FNAC-12.08, tissue
      section-12.10). The difference in AgNOR count in fibrocystic disease and fibro
      adenoma was not significant, but that between benign breast lesion and carcinoma
      was significant. No difference was observed between FNAC and tissue section
      groups in benign or malignant lesions. The simple staining technique can be used
      as an additional criterion to differentiate the benign and malignant lesions of
      breast.

PMID- 9529580
TI  - Maternal reproductive history and the occurrence of Down's syndrome.
AB  - Reproductive history of mothers of 115 Down's syndrome children was studied and
      compared with 200 control mothers who gave birth to normal children. The
      frequency of spontaneous abortions in mothers of Down's syndrome babies was found
      to be elevated significantly (p < 0.05). The data suggest that the maternal
      health and reproductive potential have a prominent aetiological significance in
      the occurrence of Down's syndrome.

PMID- 9529581
TI  - A study of the distribution of ABO and Rh(D) blood groups amongst Lodha tribe in
      Midnapore district of West Bengal.
AB  - Distribution of ABO and Rh(D) blood group was studied in 206 Lodha subjects
      living in the Midnapore district of West Bengal. It was observed that incidence
      of group A was maximum and incidence of group AB was minimum; 99.5% of the
      subjects were 'Rh' positive. The highest incidence of group A amongst Lodhas
      indicates that they might belong to the proto-Australoid group anthropologically.

PMID- 9529582
TI  - Role of hysteroscopy in infertile women.
AB  - The diagnostic accuracy and therapeutic value of hysteroscopy were evaluated in
      32 infertile women aged 21-35 years who underwent the procedure as part of their
      infertility evaluation. In 19 cases (59.4%) visually recognisable abnormalities
      were detected on hysteroscopy. These included intra-uterine adhesion (25%),
      submucous fibroid (9.4%), endometrial atrophy (9.4%), uterine septum (6.1%) and
      muellerian fusion defect (6.1%). The results of hysterosalpingography
      corresponded with hysteroscopy in 56.2% cases with a false positive of 30.7% for
      hysterosalpingography over hysteroscopy, and a false negative of 52.6%. Adhesion,
      fibroid and uterine septum accurately diagnosed were treated under hysteroscopic
      visualisation in the same sitting.

PMID- 9529583
TI  - Pre-labour rupture of membrane: the histological study of membrane and
      bacteriological profile.
AB  - One hundred two (102) cases of pre-labour rupture of membrane (PROM) were studied
      and special attention was given to the histological study of the amniotic
      membrane as well as to the bacteriological study of high vaginal flora, cervical
      flora and flora of amniotic fluid, in search of probable causes or factors
      leading to PROM. The incidence was found to be 3.16% in the age group of 20-25
      years without any relation to parity; and the duration of gestation was 38 to 40
      weeks in most of the cases. The histological study revealed: (a) Focally denuded
      amniotic epithelium, focally separated amniotic epithelium from chorion layer,
      lesser density of focal squamoid change of the epithelium and thicker chorion
      layer probably indicating focal immaturity of the chorio-amnion, (b) lesser
      thickness of collagen layer, focal hydropic degeneration and mild cellular
      infiltrate, (c) presence of focal hyaline degeneration and focal calcification of
      chorio-amnion. Microbial culture revealed: (a) Higher rate of positive culture in
      high vaginal swab, cervical swab and amniotic fluid showing presence
      predominantly of Esch coli, Strept haemolyticus, klebseilla species, Staph
      aureus, Strept non-haemolyticus, proteus species and pseudomonas species against
      that of positive cultures in the control cases, (b) no anaerobic bacteria from
      high vaginal swab, cervical swab or from amniotic fluid. It was presumed that
      focal immaturity of chorio-amnion or focal irregularity in the chorio-amnion at
      the microscopical level, focal degeneration of collagen superadded with bacterial
      infection, however mild, could be the factors leading to weakness in the tensile
      strength of chorio-amnion, again leading to PROM, in the face of stress factors
      of foetal origin.

PMID- 9529584
TI  - Alcohol problems in a general hospital--a prevalence study.
AB  - The prevalence of problem drinking among medical and surgical in-patients in a
      general hospital was studied using the CAGE questionnaire. Almost a quarter
      (23.3%) of the in-patients had associated drinking problems which were more among
      medical than surgical in-patients. In a large majority of these patients, the
      associated problem drinking was not recognised by the treating medical
      professionals. Routine administration of instruments like CAGE which are brief
      and easy to use would contribute to the early detection and management of alcohol
      problems in the general hospital setting.

PMID- 9529585
TI  - Metabolism of magnesium in health and disease.
AB  - Magnesium (Mg) is an intracellular cation. It is an essential element which
      catalyses more than 300 enzymatic reactions, in particular those involving ATP.
      Approximately half of the total Mg in the body is present intracellularly in soft
      tissues, and the other half is present in bone. Serum Mg determination represents
      only 1% of total body's Mg concentration. Modern instruments will soon be
      available to determine physiologically active intracellular ionised Mg. Despite
      the ubiquitous nature of Mg, low serum Mg occurs either from decreased absorption
      or due to increased excretion. Hypomagnesaemia is surprisingly common in hospital
      populations and is more prevalent in acute than in chronic cases but often
      remains undetected or overlooked. Magnesium deficiency may result in hypokalaemia
      and hypocalcaemia. Myocardial Mg depletion may result in influx of Na+ and Ca+2
      into the mitochondria which may lead to myocardial cell death. Hence, low Mg
      concentration may be a factor for a wide variety of clinical conditions.

PMID- 9529586
TI  - Hypertensive crisis--an overview.

PMID- 9529587
TI  - Privatisation of health care.

PMID- 9529588
TI  - Hospital waste management.

PMID- 9529589
TI  - Cystic hamartoma of the liver in children.

PMID- 9529590
TI  - Ureteral injury at appendicectomy--a case report.

PMID- 9529591
TI  - Primary squamous cell carcinoma of bone.

PMID- 9529592
TI  - Intrathoracic gastric volvulus--acute and chronic presentation.

PMID- 9529593
TI  - Familial hypercholesterolaemia with supravalvular aortic stenosis.

PMID- 9529594
TI  - Pedunculated gastric teratoma: a case report with review of literature.

PMID- 9529595
TI  - Coeliac disease: a case report.

PMID- 9529596
TI  - Otolaryngology update.

PMID- 9529597
TI  - High time to look back.

PMID- 9529599
TI  - Oncogenes and cell proliferation. Cancer genes: lessons from genetics and
      biochemistry.

PMID- 9529600
TI  - Functions of the BRCA1 and BRCA2 genes.
AB  - Mutations in the BRCA1 and BRCA2 genes confer a high risk of breast cancer
      development. Both genes encode very large proteins of unknown function but recent
      results suggest that they may have roles in transcriptional regulation and DNA
      repair. These advances offer the prospect of understanding not only the normal
      cellular function of these genes but also how their loss leads to tumour
      formation.

PMID- 9529601
TI  - Control of pRB phosphorylation.
AB  - Two opposing enzymatic reactions control the activity of the retinoblastoma
      tumour suppressor protein, pRB. Phosphorylation inactivates pRB's ability to
      sequester miscellaneous cellular proteins, mostly involved in regulating gene
      transcription, whereas pRB dephosphorylation restores this ability. For some time
      now it has been suspected that members of the cyclin/cyclin-dependent kinase
      (cyclin/cdk) family mediate pRB inactivation. Recent results indicate that pRB
      phosphorylation is not executed by single kinase but by a combination of
      cyclin/cdks, each one phosphorylating a subset of pRB's phosphorylation sites.
      The different kinases appear to be activated by growth factors through distinct
      signal transduction pathways. This lends itself to an attractive model whereby
      pRB phosphorylation may constitute an integration point for these signalling
      pathways, perhaps allowing cell cycle progression only when concurrent activation
      of these signalling pathways has been achieved.

PMID- 9529602
TI  - Regulation of cell proliferation by the E2F transcription factors.
AB  - Experimental data generated in the past year have further emphasized the
      essential role for the E2F transcription factors in the regulation of cell
      proliferation. Genetic studies have shown that E2F activity is required for
      normal development in fruitflies, and the generation of E2F-1(-/-) mice has
      demonstrated that individual members of the E2F transcription factor family are
      likely to have distinct roles in mammalian development and homeostasis.
      Additional mechanisms regulating the activity of the E2F transcription factors
      have been reported, including subcellular localization and proteolysis of the
      E2Fs in the proteasomes. Novel target genes for the E2F transcription factors
      have been identified that link the E2Fs directly to the initiation of DNA
      replication.

PMID- 9529603
TI  - Proteolysis and the G1-S transition: the SCF connection.
AB  - Temporal control of ubiquitin-proteasome mediated protein degradation is critical
      for normal G1 and S phase progression. Recent work has shown that central to the
      temporal control mechanism is a relationship between newly identified E3
      ubiquitin protein ligases, designated SCFs (Skp1-cullin-F-box protein ligase
      complexes), which confer substrate specificity on ubiquitination reactions and
      the activities of protein kinases that phosphorylate substrates destined for
      destruction at specific sites, thereby converting them into preferred targets for
      ubiquitin modification catalyzed by SCFs. The constituents of SCFs are members of
      evolutionary conserved protein families. SCF-based ubiquitination pathways may
      play a key role in diverse biological processes, such as cell proliferation,
      differentiation and development.

PMID- 9529604
TI  - Ras versus cyclin-dependent kinase inhibitors.
AB  - In the past year, complex interactions between Ras and the cell cycle have been
      identified. In primary cells, activated Ras induces a cell-cycle arrest via the
      induction of cyclin-dependent kinase inhibitors (CDKIs). Oncogenic changes that
      cooperate with Ras act by neutralising CDKIs by various mechanisms. In the
      absence of a negative growth signal from Ras, such as in most immortalised cell
      lines, Ras acts positively on the cell cycle. Insights have been made into the
      mechanisms by which Ras abrogates remaining cell-cycle controls.

PMID- 9529605
TI  - Ras signalling and apoptosis.
AB  - Activated Ras proteins have either positive or negative effects on the regulation
      of apoptosis depending on cell type and other factors. In part, this is due to
      the ability of Ras to control directly multiple effector pathways, including PI3
      kinase, which provides a universal survival signal, and Raf, which can inhibit
      survival. The mechanisms remain partly unclear, however, especially with regard
      to Raf effects on apoptosis regulation. Recently Ras has been shown to be able to
      protect cells from apoptosis either through activation of PKB/Akt via PI3-kinase,
      or through activation of NF-kappa B.

PMID- 9529606
TI  - Mechanism of activation and function of protein kinase B.
AB  - The past year has seen significant advances in our understanding of how protein
      kinase B (PKB) is activated and of the central role it plays in insulin
      signalling and in mediating the protective effects of survival factors against
      apoptosis. The highlights include the discovery of a protein kinase required for
      the 3-phosphoinositide-dependent activation of PKB and the identification of
      several physiological substrates for PKB.

PMID- 9529607
TI  - Regulation of inositol lipid kinases by Rho and Rac.
AB  - Rho and Rac small GTPases associate with type-I phosphatidylinositol 4-phosphate
      5-kinase to regulate the production of phosphatidylinositol 4,5-bisphosphate.
      This lipid appears to mediate some of the effects of Rho and Rac on the actin
      cytoskeleton. The genes for several type-I phosphatidylinositol 4-phosphate 5
      kinases have been cloned recently but it is not known which one interacts with
      Rho and/or Rac. Rho family GTPases also interact with phosphatidylinositol 3
      kinase, though this kinase can be either upstream or downstream of the GTPases
      depending upon the system.

PMID- 9529608
TI  - The Bcl-2 family and cell death regulation.
AB  - Members of the Bcl-2 protein family fall into two categories on the basis of
      their ability to either promote or suppress apoptosis. Recent findings have
      linked these proteins to caspases, the cysteine proteases that effect the
      collapse of the cell via binding to CED-4. It seems that Bcl-2 proteins influence
      cell survival by regulating the activation of key caspases.

PMID- 9529609
TI  - Myb proteins in life, death and differentiation.
AB  - Myb transcription factors are crucial to the control of proliferation and
      differentiation in a number of cell types but their mechanism of action is
      unclear. Regulation of Myb proteins by phosphorylation and intermolecular
      cooperation has recently been demonstrated, together with a new role for the
      proteins, in the control of apoptosis.

PMID- 9529610
TI  - The fight of viruses against apoptosis.
AB  - The induction of apoptosis of virus-infected cells is an important host defense
      mechanism against invading pathogens. Some viruses express anti-apoptotic
      proteins that efficiently block apoptosis induced by death receptors or in
      response to stress signaled through mitochondria. Viral interference with host
      cell apoptosis leads to enhanced viral replication and may promote cancer.

PMID- 9529611
TI  - The patched gene in development and cancer.
AB  - The cloning of vertebrate homologues of the Drosophila segment polarity gene
      patched has led to confirmation of a role for the multipass transmembrane protein
      which it encodes as a receptor for secreted signalling proteins of the Hedgehog
      family. In addition, human patched has been identified as a tumour suppressor
      gene implicated in basal cell carcinomas and medullablastomas.

PMID- 9529612
TI  - Beta-catenin: a key mediator of Wnt signaling.
AB  - Beta-catenin is a pivotal player in the signaling pathway initiated by Wnt
      proteins, mediators of several developmental processes. beta-catenin activity is
      controlled by a large number of binding partners that affect the stability and
      the localization of beta-catenin and is thereby able to participate in such
      varying processes as gene expression and cell adhesion. Activating mutations in
      beta-catenin and in components regulating its stability can contribute to the
      formation of certain tumors.

PMID- 9529613
TI  - SMADs: mediators and regulators of TGF-beta signaling.
AB  - The discovery of SMAD proteins has allowed the delineation of a mechanism by
      which TGF-beta and related growth factors convey their signals from membrane
      receptors all the way into the nucleus. SMADs are directly phosphorylated and
      activated by the receptors and then form heteromeric SMAD-SMAD complexes that
      move into the nucleus where they orchestrate transcriptional responses. In rapid
      succession, recent reports have identified different modes of SMAD regulation by
      phosphorylation and have defined the SMAD domains that mediate SMAD interactions,
      binding to DNA or transcriptional activation. The recent discovery of
      antagonistic SMADs and regulatory crosstalk with Ras/MAP-kinase pathways add to
      our rapidly expanding understanding of this major regulatory network.

PMID- 9529614
TI  - Genetic analysis of protein tyrosine phosphatases.
AB  - Genetic analysis has enhanced our understanding of the biological roles of many
      protein tyrosine kinases (PTKs). More recently, studies utilizing both
      spontaneous mutants and mutants induced by homologous recombination techniques
      have begun to yield key insights into the role of specific protein tyrosine
      phosphatases (PTPs) and to suggest how PTKs and PTPs interact. Specific PTPs in
      Saccharomyces cerevesiae and Schizomyces pombe regulate MAP kinase pathways.
      Several Drosophila receptor PTPs control axonal targeting pathways, whereas the
      non-receptor PTP Corkscrew (Csw), plays an essential positive signaling role in
      multiple developmental pathways directed by receptor PTKs. The vertebrate homolog
      of Csw, SHP-2, also is required for growth factor signaling and normal
      development. Finally, very recent studies of other mammalian PTPs suggest that
      they have critical roles in processes as diverse as hematopoiesis and liver and
      pituitary development.

PMID- 9529615
TI  - Blood pressure control, proteinuria and renal outcome in chronic renal failure.
AB  - The presence of proteinuria has been shown to be an excellent predictor for a
      worse outcome of renal function. Both proteinuria and arterial hypertension often
      coexist in the same patient, and therapy must be directed at decreasing protein
      excretion in the urine as well as lowering the blood pressure. Any
      antihypertensive agent has the capacity to lower proteinuria simply by lowering
      blood pressure. Furthermore, the antiproteinuric capacity of angiotensin
      converting enzyme inhibitors can be equalized by other agents or their
      combination, provided that the fall in blood pressure is great enough. For this
      reason studies are needed in which the strict control of arterial hypertension
      combined with a decrease in proteinuria are considered.

PMID- 9529616
TI  - Renal endothelial function in humans.
AB  - Animal experiments have shown extensively that the endothelial generation of
      nitric oxide participates in the regulation of renal haemodynamics and function,
      probably as a factor modulating the effects of endogenous vasoconstrictors.
      Although the endothelial function of the systemic vasculature is assessed through
      the vasodilatory effect of acetylcholine, only L-arginine infusion is available
      for studies of the influence of nitric oxide on the renal circulation in humans.
      In addition to peripheral vessels, L-arginine is a potent renal vasodilator,
      having no effect on the glomerular filtration rate; and the renal relaxation
      induced by L-arginine is markedly blunted in patients with essential
      hypertension. A few studies showing the renal vasoconstrictor effect of an
      inhibitor of nitric oxide synthesis have been reported.

PMID- 9529617
TI  - Renal effects of renin-angiotensin system blockade.
AB  - Pharmacological interruption of the renin-angiotensin system at different pathway
      levels has extended our knowledge on the distribution of angiotensin receptors in
      different nephron segments, its regulation and tubular cell responses. Novel
      beneficial effects obtained with blockade of this peptide on cellular
      proliferation and its interaction with other vasoactive systems are particularly
      important for preventing renal damage.

PMID- 9529618
TI  - New insights into polycystic kidney disease and its treatment.
AB  - Major advances in the understanding of the genetics and pathogenesis of autosomal
      dominant polycystic kidney disease have occurred within the past year. The
      proteins encoded by the PKD1 and PKD2 genes, polycystin 1 and polycystin 2, are
      membrane proteins, capable of interacting physically in vitro, and are likely
      components of a complex signalling pathway. The majority of PKD1 and PKD2
      mutations so far identified are unique inactivating mutations dispersed over the
      entire genes. Immunohistochemical studies have shown that polycystin 1 and
      polycystin 2 are developmentally regulated and are overexpressed in polycystic
      kidneys. The cysts probably result from clonal expansions of single cells. The
      demonstration of loss of heterozygosity for PKD1 and the absence of
      immunoreactive polycystin 1 in approximately 20% of the cysts supports a two-hit
      tumor suppressor gene model of cystogenesis. Regardless of the nature of the
      initial pathogenic mechanism, the cysts in autosomal dominant polycystic kidney
      disease are accompanied by partial dedifferentiation of the epithelial cells,
      disregulation of epithelial cell proliferation, expression of a secretory
      phenotype, and disarray of cell matrix interactions which leads to interstitial
      inflammation and matrix accumulation. Recent observations in animal models of
      inherited polycystic kidney disease have implicated oxidative stress in its
      pathogenesis. These downstream pathogenetic events have been targeted for
      intervention, and an increasing number of studies have demonstrated that the
      course of polycystic kidney disease in rodents can be altered by environmental
      and pharmacological interventions. Nevertheless, these experimental observations
      cannot be extrapolated to human autosomal dominant polycystic kidney disease. The
      recent generation of mice with PKD1 or PKD2 targeted mutations will help to
      bridge this gap.

PMID- 9529619
TI  - Calcium antagonists and the progression of chronic renal failure.
AB  - End-stage renal disease, which signifies irreversible renal failure, constitutes
      a major and growing public health problem worldwide. The striking increase in end
      stage renal disease has catalyzed clinical and investigative focus on
      pharmacologic interventions to retard progression to this condition. Increasing
      evidence indicates that some classes of antihypertensive medications may confer a
      greater effect than others in slowing progression of renal disease despite
      similar levels of blood pressure reduction. Substantive data indicate that
      angiotensin converting enzyme inhibition preferentially retards the progression
      of renal disease, primarily by protecting the injured kidney from hemodynamically
      mediated glomerular damage. Newer studies suggest that calcium antagonists also
      have diverse properties, which are independent of their renal microcirculatory
      effects that might afford renal protection.

PMID- 9529620
TI  - Hepatitis C virus and renal transplantation.
AB  - During the past 12 months additional evidence has emerged from several studies,
      indicating that hepatitis C virus infection is the most important liver disease
      after renal transplantation. A new, severe and rare entity called fibrosing
      cholestatic hepatitis can lead to early liver failure, although the most
      important complications appeared in the long-run. Encouraging results with
      ribavirin have been described. Although glomerular lesions and more severe
      infections can appear in hepatitis C virus patients, graft and patient survival
      rates in most series are similar to those in hepatitis-C-negative patients.
      Survival is also better among hepatitis-C-positive patients after renal
      transplantation than in hepatitis-C-positive patients on dialysis on the waiting
      list for transplantation. Finally, the use of kidneys from hepatitis-C-positive
      donors is suggested for transplant into hepatitis C RNA positive patients
      matching the hepatitis C genotype.

PMID- 9529621
TI  - Evidence-based medicine.

PMID- 9529622
TI  - Ouabain-like factor.
AB  - Accumulated evidence has suggested that several sodium pump inhibitors, similar
      to cardiotonic steroids, are present in the human body. Ouabain-like factor, the
      most appealing candidate, has been found to be increased with high sodium intake
      and hypervolaemia, and in essential hypertension, mineralocorticoid hypertension,
      and pregnancy-induced hypertension. Furthermore, blocking the action of ouabain
      like factor with digibind or a novel anti-ouabain agent lowers blood pressure in
      several models of hypertension. Several important questions remain, however,
      before it can be concluded that ouabain-like factor is indeed involved in the
      regulation of sodium homeostasis and blood pressure.

PMID- 9529623
TI  - Nitric oxide and renal blood pressure regulation.
AB  - In the mammalian body the kidney might be the most important organ for long-term
      blood pressure regulation. Nitric oxide seems to play a particular role in the
      control of renal haemodynamics, and changes in renal nitric oxide synthesis
      should therefore be of great importance for the renal control of blood pressure.

PMID- 9529624
TI  - The role of endothelium in human hypertension.
AB  - Endothelium-derived nitric oxide is not only a potent vasodilator but also
      inhibits platelet aggregation, smooth muscle cell proliferation, monocyte
      adhesion and adhesion molecule expression. In several pathological conditions,
      such as human hypertension, nitric oxide availability is reduced. This alteration
      has been documented in the peripheral and coronary micro- and macrocirculation
      and in the renal circulation. The main mechanism leading to endothelial
      dysfunction is production of cyclooxygenase-dependent factors, including
      prostanoids and oxygen free radicals, which cause nitric oxide breakdown.
      Dysfunctional endothelium can be one of the main mechanisms causing vascular
      damage, in particular, atherosclerosis; hence, an important aim for
      antihypertensive treatment could reside not only in normalizing blood pressure
      values but also in reversing endothelial dysfunction. Available evidence
      indicates that different classes of antihypertensive compounds have different
      effects on endothelial dysfunction.

PMID- 9529625
TI  - Cardiac hypertrophy and hypertension.
AB  - In the general population and in patients with essential hypertension the
      presence of left ventricular hypertrophy is a powerful predictor of
      cardiovascular events, independent of blood pressure and other cardiovascular
      risk factors. The prevalence of left ventricular hypertrophy increases with age
      and with the severity of renal impairment. Left ventricular hypertrophy is also a
      sensitive indicator of vascular structural changes in both large and small
      arteries. The possibility of reversing left ventricular hypertrophy therefore
      represents a major therapeutic goal for the treatment of hypertensive patients.
      Several studies examining the characteristics of left ventricular hypertrophy in
      the elderly, the interrelations between cardiac and vascular hypertrophy, the
      possibility of reversing left ventricular hypertrophy and its consequent
      prognostic value will be reported and commented on in the present review.

PMID- 9529626
TI  - Pharmacogenomics: a new approach to individual therapy of hypertension?
AB  - The individual variation in the efficacy of and tolerability to antihypertensive
      drugs in human essential hypertension is linked to the genetic heterogeneity of
      this multifactorial disease. Different approaches have been pursued in the
      attempt to correlate a specific responsiveness to the therapy with some
      phenotypic traits of the patients, such as the renin-angiotensin profile or the
      characteristics of cell ion transports. More recently, a genetic approach to the
      study of the mechanisms underlying hypertension has led to the identification of
      some quantitative trait loci or genes that influence blood pressure in both
      animal models and patients. Also, individual variation to therapy can now be
      studied from the genetic point of view using pharmacogenomics, that is, the study
      of the genes or loci which are involved in determining the responsiveness to a
      given drug. Only a few examples of this approach are available to date. Our group
      has identified a polymorphism of the genes for the cytoskeletal protein, adducin,
      which is linked to both rat and human hypertension, sodium sensitivity and to the
      pressor responsiveness to diuretic therapy. These results, together with the
      indication that adducin can play a functional role by modulating the cellular
      sodium transport, have led to the identification of a new antihypertensive
      compound, which could be a candidate for the selective treatment of those
      patients in whom alterations of the renal sodium handling are associated with
      specific genetic traits such as the polymorphism for adducin.

PMID- 9529627
TI  - Clinical nephrology.

PMID- 9529628
TI  - Pathophysiology of hypertension.

PMID- 9529629
TI  - Is bronchiolitis an obsolete term?

PMID- 9529630
TI  - Prevention and control of tetanus in childhood.
AB  - Until recently, tetanus was estimated to be killing well over half a million
      children each year in the developing world, most commonly through neonatal
      tetanus, the incidence of which was around six per 1000 live births. Neonatal
      tetanus most commonly occurs through cord contamination of the umbilical stump.
      Vaccination of pregnant women and infants is an effective and inexpensive
      intervention that results in major health gains, although educating traditional
      birth attendants and mothers about safer birthing practices probably also lowers
      the incidence of tetanus. Recently, however, new vigor and strategies in
      immunization programs have resulted in substantial improvements. Immunization of
      pregnant women, and identification and targeting of areas and populations in
      which neonatal tetanus is occurring are especially effective. Tetanus will
      continue to be a pediatric problem until vaccination strategies are effectively
      implemented, surveillance systems are improved, and hygienic birthing practices
      become standard in all countries.

PMID- 9529631
TI  - Otitis media.
AB  - Despite extensive research on various aspects of otitis media, this disease
      remains an important health care problem of childhood. The rapid increase in
      resistance to penicillin and several other drugs among strains of Streptococcus
      pneumoniae will most likely have a great impact on the antibiotic treatment of
      acute otitis media. The increasing antimicrobial resistance has once again
      brought up the question of whether antibiotics are really needed in the treatment
      of acute otitis media. Further, the resistance problem underscores the great need
      for effective methods to prevent otitis media. In the current situation, the
      common practice of using antimicrobial prophylaxis for prevention of otitis media
      should be seriously reconsidered.

PMID- 9529632
TI  - Bacterial meningitis and meningococcal infection.
AB  - Now that invasive disease caused by Haemophilus influenzae type b has been
      largely controlled in the developed world, the principal bacterial pathogen
      causing meningitis in most countries is the meningococcus. Serogroup B and C
      strains predominate in most industrialised countries in contrast to the situation
      in sub-Saharan Africa, where serogroup A meningococcal disease is periodically a
      problem of massive epidemic proportions. This review focuses on developments in
      our understanding of the diagnosis and treatment of meningococcal disease, of
      host factors important in susceptibility to, and severity of, this infection, and
      on advances which may eventually lead to its prevention.

PMID- 9529633
TI  - Helicobacter pylori infection in children.
AB  - Helicobacter pylori causes chronic gastritis and peptic ulcer disease and is
      epidemiologically associated with the subsequent development of gastric
      malignancies. Knowledge regarding H. pylori is of particular relevance to
      pediatricians since acquisition of the infection occurs mainly during the
      childhood years and may be associated with the development of more severe disease
      manifestations such as gastric malignancies. Because only a minority of infected
      individuals will ever develop the sequelae of peptic ulcer disease or gastric
      cancer, the identification of bacteria factors that play a role in disease
      pathophysiology is a major focus of current research. This review highlights
      recent advances in our knowledge of disease pathogenesis, with particular
      emphasis on bacterial virulence. In addition, the recent literature addressing
      epidemiology, transmission, clinical features, treatment, and prevention of H.
      pylori infection is reviewed.

PMID- 9529634
TI  - Kawasaki disease thirty years on.
AB  - This year marks the 30th anniversary of the first description of Kawasaki
      disease. The disease has emerged as an important cause of acquired heart disease
      in children. The cause of Kawasaki disease remains unknown and this presents many
      problems in the diagnosis and management of the disease. This paper reviews
      recent publications on the pathogenesis, diagnosis, and the short- and long-term
      management of Kawasaki disease.

PMID- 9529635
TI  - Emerging viruses.
AB  - An emerging virus is a term applied to a newly discovered virus, one that is
      increasing in incidence or with the potential to increase in incidence. Many
      viruses fit into this definition. HIV is the clearest example of a previously
      unknown virus that has now produced one of the largest pandemics in history.
      Recent advances have occurred in the identification and understanding of new
      hantaviruses in the Americas, causing an acute respiratory disease. The possible
      causal role of human herpesvirus 8 in Kaposi's sarcoma has gained support,
      whereas that of a newly discovered flavivirus in causing hepatitis has not been
      confirmed. A major advance has been evidence showing that the bovine spongiform
      encephalopathy agent is almost certainly the cause of a new variant of
      Creutzfeldt-Jakob disease. Although new viruses are discovered almost yearly
      (e.g., Australian bat lyssavirus), other "older" viruses (e.g., dengue) are
      reemerging, infecting millions of people every year with significant mortality.

PMID- 9529636
TI  - New antibiotics.
AB  - Three broad-spectrum antibiotics are reviewed, each from a different class.
      Meropenem is closely related to imipenem and was recently approved for use in
      children. Its advantages over imipenem include greater activity against gram
      negative bacteria and lack of association with seizures. Cefepime is a fourth
      generation cephalosporin with the gram-positive activity of cefotaxime and the
      gram-negative spectrum of ceftazidime. Trovafloxacin is a fluoroquinolone with an
      exceptionally broad antibacterial spectrum. Meropenem is approved for use in
      children, cefepime is approved for use in adults only, and trovafloxacin is still
      undergoing clinical trials. These agents should be reserved for treatment of
      serious infections, especially those in immunocompromised patients or
      polymicrobial infections.

PMID- 9529637
TI  - Hematology and oncology.

PMID- 9529638
TI  - The natural history of sickle cell disease.
AB  - Sickle cell disease results in significant morbidity and mortality for those
      affected with this disease. Despite the fact that every case of sickle cell
      disease results from the same genetic mutation, there is considerable
      heterogeneity in the clinical course of the disease. Considerable knowledge has
      been gained regarding the complications of sickle cell disease including pain
      episodes, infections, stroke, and lung disease. Clarifying the clinical course of
      sickle cell disease has enabled us to develop therapies to decrease the morbidity
      of this disease and, with hope, will direct further investigations into novel
      treatment interventions.

PMID- 9529639
TI  - An update on transfusion-transmitted viruses.
AB  - Advances in blood donor screening have advanced the concept that a zero-risk
      blood supply may be possible in the future. Although the application of a large
      number of serologic tests and more stringent donor questioning has certainly
      aided our ability to screen out donors, risks still remain. In this article, the
      literature on some transfusion transmitted diseases is reviewed.

PMID- 9529640
TI  - Biology of thrombopoietin.
AB  - Thrombopoietin is a hematopoietic growth factor that stimulates megakaryopoiesis.
      Recent results indicate that thrombopoietin has multilineage hematopoietic
      effects both in vitro and in vivo. Clinical studies of thrombopoietin have begun,
      and are reviewed.

PMID- 9529642
TI  - Orthopedics.

PMID- 9529641
TI  - The Fanconi anemia genes.
AB  - Until recently, it had been thought that Fanconi anemia patients were distributed
      into five complementation groups. However, evidence now points to the existence
      of three new complementation groups, making the genetic basis of the disease more
      complicated than anticipated. Also, during the past year, the cloning of a second
      Fanconi anemia gene by both functional complementation and positional cloning has
      accelerated research of this disease. Although two genes of the eight
      characterized complementation groups have now been cloned, the function of their
      gene products still needs to be identified.

PMID- 9529643
TI  - Childhood osteomyelitis and septic arthritis.
AB  - The diagnosis, treatment, and monitoring of septic arthritis or osteomyelitis in
      children has become more streamlined in recent years. C-reactive protein appears
      to be a better laboratory study than sedimentation rate in the diagnosis of bone
      or joint infection and in monitoring a patient's clinical response to
      antibiotics. Oral antibiotics may be rapidly substituted for intravenous
      antibiotics in patients who have a identifiable sensitive organism, who show
      rapid clinical improvement, and who show rapid normalization of C-reactive
      protein. The physician must remain alert for resistant organisms, highly virulent
      organisms (post-varicella streptococcal infections) and rare organisms.

PMID- 9529644
TI  - Determining treatment of flatfeet in children.
AB  - Infants are born with flexible flatfeet, and the normal arch develops in the
      first decade of life. Flexible flatfeet rarely cause disability, and asymptomatic
      children should not be burdened with orthotics or corrective shoes. Flexible
      flatfeet with tight heelcords may become symptomatic and can be addressed with a
      stretching program. Surgical intervention for flexible flatfeet is reserved for
      patients who have persistent localized symptoms despite conservative care. Rigid
      or pathologic flatfeet have multiple etiologies and many will require treatment
      to alleviate symptoms or improve function.

PMID- 9529645
TI  - Pediatric spinal deformity.
AB  - Pediatric spinal deformity is a common problem facing the pediatrician and
      orthopedic surgeon. Most commonly seen is idiopathic scoliosis. Early diagnosis
      and treatment are important. Although the etiology of idiopathic scoliosis
      remains unclear, there continues to be a search for genetic markers and studies
      for the modes of inheritance. Idiopathic scoliosis is more clearly understood
      recently and is recognized as a complex three-dimensional deformity. Prognostic
      indicators for juvenile scoliosis have been identified. Surgical management of
      idiopathic scoliosis continues to evolve, and now a thoracoscopic endoscopic
      technique is available. Long-term follow-up has demonstrated generally
      satisfactory results with spinal fusion surgery. Other syndromes such as Klippel
      Feil, familial dysautonomia, and Marfan syndrome demonstrate high rates of
      scoliotic deformities. Most are unresponsive to bracing and most often require
      surgical intervention. Although primary spinal neoplasms are uncommon, most are
      benign, and outcomes are generally satisfactory.

PMID- 9529646
TI  - Diagnosis and treatment of unicameral and aneurysmal bone cysts in children.
AB  - Bone cysts are commonly encountered clinical problems in the pediatric age group.
      The most common types of cysts are the unicameral and aneurysmal bone cysts.
      These benign lesions vary in their aggressiveness, clinical behavior and
      treatment. Both of these lesions are poorly understood in terms of their
      etiology, but effective treatment exists. These lesions represent a source of
      great consternation to both clinicians and families, for they weaken the bone and
      may be confused with malignant lesions. This review will focus on the two most
      commonly encountered cystic lesions in the pediatric population.

PMID- 9529647
TI  - Leg lengthening in children.
AB  - Leg lengthening techniques, imported from Russia and Europe, have developed
      during the past 10 years in North America and have matured to become an accepted
      method of treating leg length discrepancy. The use of these techniques for
      stature lengthening in dwarfism is somewhat less widespread. A review of
      published reports indicates a maturation in the field of leg lengthening, with
      more focused studies on larger cohorts of patients having the same pathology.
      Long-term follow-up studies are forthcoming, and there is still extensive room
      for basic research. Precise indications and limits for lengthening in femoral
      hypoplasia and fibular hemimelia are unclear, and await additional reporting.
      Future research needs to include outcome studies, hardware improvements,
      implantable lengthening devices, and a better understanding of the basic science
      behind lengthening of both bone and soft tissues.

PMID- 9529648
TI  - Osteomyelitis masquerading as renal stones.

PMID- 9529649
TI  - Fever without apparent source on clinical examination, infectious diseases, and
      lower respiratory infections in children.
AB  - This section focuses on issues in infectious diseases that are commonly
      encountered in pediatric office practice. Paul McCarthy discusses recent
      literature regarding the evaluation and management of acute fevers without
      apparent source on clinical examination in infants and children, and the
      evaluation of children with prolonged fevers of unknown origin. Jean Klig reviews
      recent literature about lower respiratory tract infection in children. Jeffrey
      Kahn and Eugene Shapiro discuss recent developments in pediatric infectious
      diseases concerning neonatal herpes infections, poliovirus immunization schedule,
      and group B streptococcus screening and treatment.

PMID- 9529650
TI  - Role of infection in autoimmune disease.

PMID- 9529651
TI  - The role of infection in the pathogenesis of autoimmune disease.
AB  - Autoimmune disease has long been considered a shadow following infectious
      diseases. Epidemiological evidence shows that rheumatic fever follows
      streptococcal infection and Trypanosoma cruzi infection is the instigator of
      Chagas' disease. There is, however, very little information of the mechanism by
      which such a train of events is initiated. Autoimmunity, in a form of
      autoantibodies, is common after many infections and may well result from the
      mimicking of host proteins by antigens of the infectious agent. There are,
      however, few if any examples in humans where molecular mimicry gives rise to
      autoimmune disease. The progression from benign autoimmunity to pathogenic
      autoimmune disease depends upon the balance of cytokines produced during the
      inflammatory process accompanying infection. In many autoimmune diseases, the
      cytokine profile favors the proinflammatory cytokines, IFN-gamma and IL-1, which
      support the production of disease. A searching study of cytokine profiles during
      infection may offer a promising approach to avoiding the harmful consequences of
      post-infection autoimmune responses.

PMID- 9529652
TI  - Unraveling the mystery of HLA-B27 association with human spondyloarthropathies
      using transgenic and knock out mice.
AB  - Human spondyloarthropathies have a strong association with the presence of MHC
      class I allele, HLA-B27. Spondyloarthropathies occur predominantly in males and
      are usually triggered by an infection with an enterobacteria. Similar to human
      disease, experimental animals with HLA-B27 transgene also develop spontaneous
      inflammatory disease. In addition to HLA-B27, the role of environmental antigens
      has also been implicated in the animal models. How bacteria interact with HLA-B27
      is not yet clearly understood. By breeding HLA-B27 transgenic mice with various
      transgenic and knock out mice, we investigated the immune mechanism in this
      inflammatory disease. In this review, we will summarize our recent findings and
      propose a hypothesis.

PMID- 9529653
TI  - Molecular mimicry between non-self, modified self and self in autoimmunity.
AB  - Molecular mimicry, the presence of shared epitopes between foreign and self
      antigens is common both at the B and T cell level. That it only rarely leads to a
      cross-reactive autoimmune response is a testimony to the effectiveness of the
      immune system in regulating the immune response and avoiding harmful self
      reactivity. However, despite this regulation, various auto-immune-mediated
      diseases have been associated with molecular mimicry. The concept of molecular
      mimicry between foreign and self antigen as well as between self and modified
      self epitopes is reviewed and the relevance of these phenomena for the initiation
      of autoimmune diseases is discussed.

PMID- 9529654
TI  - T cell responses to conserved bacterial heat-shock-protein epitopes induce
      resistance in experimental autoimmunity.
AB  - The relationships between bacterial heat shock proteins (HSPs) and autoimmunity
      were first disclosed in the mycobacteria-induced model of adjuvant arthritis:
      passive transfer of a T cell clone responding to mycobacterial HSP60 evoked
      disease in naive recipient animals. However, the disease could not be induced by
      immunization with HSP60, but instead protection was established. Subsequently,
      similar protection was found in experimental models of arthritis that do not
      involve challenge with bacterial antigens for the induction of disease. This
      rather general protective potency of bacterial HSPs against arthritis seems to
      result from the capacity of strongly conserved sequences in the protein to
      activate T cells that cross-recognize the mammalian homologous HSP-sequences
      presented on cells at the site of inflammation. It is possible that immunological
      recognition of bacterial HSPs is part of a general strategy used by the immune
      system for the regulatory control of the potentially harmful recognition of
      autoantigens as a hedge against the development of autoimmune disease.

PMID- 9529655
TI  - B cell superantigens: possible roles in immunodeficiency and autoimmunity.
AB  - Lymphocyte antigen receptors have evolved for the discrimination of self and non
      self structures and consequently the unconventional binding activities of
      superantigens pose a special set of potential hazards and opportunities for the
      immune system. This review presents recent evidence that certain naturally
      occurring proteins have the properties of B cell superantigens by virtue of their
      unconventional variable-region mediated interactions with soluble and membrane
      bound immunoglobulins. The implications for B lymphocyte activation and clonal
      selection are discussed and we speculate how superantigens may influence the
      development of lymphocyte repertoires and the immune responses associated with
      certain autoimmune and immunodeficiency diseases.

PMID- 9529656
TI  - Microbial peptides and superantigens in the pathogenesis of autoimmune diseases
      of the central nervous system.
AB  - The mechanisms by which microbial peptide antigens and superantigens might
      initiate and perpetuate autoimmune responses against antigens of the central
      nervous system are discussed. A model will be proposed that includes the initial
      activation of naive T lymphocytes through T cell receptor-mediated recognition of
      microbial antigens presented by MHC class II molecules. This event might be
      followed by re-activation of autoreactive T cells by bacterial and viral
      superantigens. Both mechanisms could lead to acute and relapsing autoimmune
      disease.

PMID- 9529657
TI  - Infections in the immunopathogenesis of chronic inflammatory bowel disease.
AB  - In chronic inflammatory bowel disease, self-destructive, exaggerated inflammation
      seems to occur in the absence of a well defined pathogen. However,
      epidemiological data strongly suggests that development of disease does not
      depend on endogenous factors alone. In this review, we summarize how a possible
      role for microbial factors can be reconciled with the current understanding of
      etiology and pathogenesis of IBD. The data presented does not support that IBD is
      an infectious disease nor that it is a self-antigen-specific autoimmune disease,
      however, recent findings increasingly suggest that tissue damage might be caused
      by a non-specific autoaggressive inflammation which is driven by common,
      ubiquitous microbial agents derived from the bacterial flora in the intestinal
      lumen.

PMID- 9529658
TI  - Protective and destructive effects of microbial infection in insulin-dependent
      diabetes mellitus.
AB  - Insulin-dependent diabetes mellitus (IDDM) is a T-cell mediated autoimmune
      disease, which results in the destruction of the islet beta-cells. The major
      histocompatibility complex (MHC) encodes the major susceptibility gene in IDDM.
      The concordance rate for diabetes in identical twins is 30-50% and in inbred
      animal models of disease the incidence rate is 20-80%. These results emphasize a
      role for environmental factors in the disease process. It has long been suggested
      that IDDM in humans may be caused by-viral infections. While considerable
      progress has been made in defining the genetics of IDDM, our understanding of the
      role of environmental factors, which might provide a more direct approach to
      therapy is considerably lacking. We suggest that (1) the density and affinity of
      epitopes derived from microbial antigens that bind to MHC molecules; (2) their
      cross-reactivity with beta-cell antigens; and (3) the nature of immunoregulatory
      cytokines induced by the microbial infections are the primary factors in the
      induction of either effector or protective T cells in IDDM.

PMID- 9529659
TI  - Role of viruses in type I diabetes.
AB  - Viral infections frequently elicit strong cellular and humoral immune responses.
      This bears the inherent danger of co-activating autoreactive lymphocytes, either
      through bystander activation by cytokines or through direct sharing of
      conformational determinants between self and virus (mimicry). Autoimmune diseases
      could then result, even after clearance of the viral infection, if enough
      autoreactive cells are activated. Alternatively, viral infection of antigen
      presenting cells can locally enhance inflammation and drive autoreactive
      lymphocytes. Evidence for these mechanisms, as well as emerging therapeutic
      concepts, will be discussed.

PMID- 9529660
TI  - Genetic and environmental influences on the continuous scales of the Myers-Briggs
      Type Indicator: an analysis based on twins reared apart.
AB  - The Myers-Briggs Type Indicator was administered to a sample of 61 monozygotic
      twins reared apart (MZA), 49 dizygotic twins reared apart (DZA), and 92 spouses,
      who participated in the Minnesota Study of Twins Reared Apart (MISTRA) from 1979
      to 1995. Twins' scores on the continuous scales were subjected to behavior
      genetic model-fitting procedures. Extraversion-Introversion and Thinking-Feeling
      yielded heritabilities of about .60, consisting largely of nonadditive genetic
      variance. Sensing-Intuition and Judgment-Perception yielded heritabilities of
      about .40, consisting largely of additive genetic variance. Spouse correlations
      for three of the four scales were near zero and not statistically significant;
      one spouse correlation (Sensing-Intuition) was modestly positive and
      statistically significant.

PMID- 9529661
TI  - Parental representations and support-seeking behaviors related to dependency and
      self-criticism.
AB  - Cognitive and interpersonal models of depression were integrated by examining the
      links between parental representations and the interpersonal behaviors of
      individuals at risk for depression. Study 1 assessed the quantity and type of
      social support associated with Dependency and Self-Criticism. Study 2 examined
      the parental representations related to these personality styles, in an effort to
      document cognitive variables that might contribute to interpersonal behaviors.
      Self-critics were found to be more dysphoric over a 21-day, self-monitoring
      period, made fewer requests for social support, and showed lower perceptions of
      support. Peers did not report providing less support to self-critics, but found
      them less expressive and did not know them as well. Study 2 found pervasive,
      negative parental representations associated with Self-Criticism providing a
      cognitive underpinning to social distancing. Dependent participants reported
      higher levels of support, which was corroborated by the peer reports. Study 2
      found Dependency to be related to favorable representation of parents for
      friendly and submissive, but not hostile, situations. The impact of cognitive
      representations for interpersonal functioning is highlighted, and reciprocal
      processes between the two are discussed.

PMID- 9529662
TI  - Neuroticism and reactions to social comparison information among cancer patients.
AB  - In an experimental study neuroticism was examined as a moderator of breast cancer
      patients' affective reactions to social comparison information about a fellow
      patient. Fifty-seven women with breast cancer completed Eysenck's Personality
      Questionnaire and received social comparison information about a fellow patient
      who was either doing better (upward condition) or worse (downward condition) than
      themselves. As expected, patients showed more positive reactions to upward
      comparison information than to downward comparison information. Moreover,
      neuroticism was related to responding more negatively and less positively to
      social comparison information. Although respondents high and low in neuroticism
      did not differ in their reactions to downward comparison information, low
      neuroticism was associated with more positive responding to upward comparison
      information.

PMID- 9529663
TI  - Hope and coping with cancer by college women.
AB  - The relations of dispositional hope to various self-reported cancer-related
      coping activities were examined in 115 college women. Dispositionally high- as
      compared to low-hope women were more knowledgeable about cancer, and this
      relationship remained when the shared variances due to previous academic
      achievement, experience with cancer among family or friends, and positive and
      negative affectivity were removed. Additionally, high- as compared to low-hope
      women reported more hope-related coping responses in four separate imagined
      phases of cancer (prevention/risk, detection, temporal course, and impact), and
      these relationships remained when shared variances related to previous academic
      achievement, knowledge about cancer, experience with cancer, and negative
      affectivity were removed. Hope is discussed as means of maintaining a "fighting
      spirit" for coping with cancer.

PMID- 9529664
TI  - Gender and situational context moderate the relationship between self-monitoring
      and induction of self-disclosure.
AB  - Male and female undergraduates who differed in degree of self-monitoring
      interviewed same-sex strangers to test the hypothesis that interviewer self
      monitoring propensities foster self-disclosure only in disclosure-conducive
      contexts (i.e., collaborative contexts for men and social-expressive contexts for
      women). Results indicated that high self-monitoring (but not low self-monitoring)
      interviewers of each gender were notably more successful at eliciting personal
      information in the contexts generally considered amenable to male and female self
      disclosure than in disclosure-nonconducive contexts. Moreover, male high self
      monitoring interviewers reliably elicited more information than their low self
      monitoring counterparts only in the disclosure-conducive (for men) collaborative
      context. However, high self-monitoring female interviewers did not elicit more
      information than their dispositional counterparts in disclosure-conducive, social
      expressive contexts, although they reliably induced less disclosure than low self
      monitors in the disclosure-nonconducive (for women) collaborative context.

PMID- 9529665
TI  - Validating an American scale in Hong Kong: the Center for Epidemiological Studies
      Depression Scale (CES-D).
AB  - The construct validity of a Chinese-language version of the Center for
      Epidemiological Studies Depression Scale (CES-D; Radloff, 1977) was tested on a
      sample of 138 Hong Kong Chinese married couples. Confirmatory factor analysis
      identified 2 factors: (a) depressive symptom factors and (b) interpersonal
      problem factors. Those factors attained convergent, discriminant, and structural
      validity when evaluated against social desirability. The CES-D also manifested
      nomological validity in terms of its significant relationships with measures of
      life satisfaction and stressful life events.

PMID- 9529666
TI  - Psychophysiological aspects of amphetamine-methamphetamine abuse.
AB  - Abuse of amphetamines-methamphetamines has increased worldwide. Profiles of
      abusers, effects of different methods of administration, and research on
      amphetamine psychosis are reviewed, along with research on psychophysiological
      mechanisms, addictive potential, and psychotherapeutic strategies.

PMID- 9529667
TI  - Histopathological characteristics of chronic hepatitis C virus infection in
      Turkey.
AB  - Hepatitis C virus (HCV) is the major cause of posttransfusion non-A, non-B
      hepatitis. The aim of this study is to describe the morphological changes related
      to HCV infection found in Turkey and compare the similarities and differences
      with the previous reports. Liver biopsies from 44 patients with HCV infection
      were studied. Chronic active hepatitis was the most common (56.8%)
      histopathological lesion. Most of the cases (n = 15, 34.1%) with chronic active
      hepatitis showed mild activity and mean HAI was 5.5 in these cases. The presence
      of sinusoidal lymphocytes (79.5%) and Kupffer cell proliferation (68.2%) were the
      most common histological features. We could not find any publication about
      histopathological characteristics of HCV infection from Turkey in MEDLINE
      database. This study shows that histopathological changes seen in patients with
      chronic HCV infection in Turkey is comparable with the literature, but more
      histopathological studies including genotyping of HCV and objective criteria to
      evaluate histopathological changes of chronic HCV infection are needed for
      definite conclusion.

PMID- 9529668
TI  - Prevention of vertical transmission of hepatitis B virus infection. Is there a
      standard policy in Flanders (Belgium)?
AB  - The perinatal transmission of hepatitis B virus (HBV) from mother to child can be
      effectively prevented by the combined administration of hepatitis B
      immunoglobulins (HBIg) and hepatitis B vaccine (HB vaccine) immediately after
      birth. This requires prenatal screening of all pregnant women for HBsAg. In
      Belgium, a standard prevention policy does not exist. This study evaluated the
      current prevention policy of paediatricians in Flanders, regarding the prevention
      of vertical transmission of HBV, and their knowledge regarding the reimbursement
      of the HB vaccine for neonates of HBsAg-positive mothers. Ninety-one percent out
      of 134 participants administered both HBIg and HB vaccine. The recommended
      timing, within 12 hours post-partum, was observed in 60.0% for HBIg and in 50.3%
      for HB vaccine. Twenty-five percent of the respondents answered not to be well
      informed regarding the reimbursement of the HB vaccine. A preliminary study in
      Flanders among gynaecologists showed that 27 out of 29 routinely screened
      pregnant women for HBV, but the type of serology tested and the timing of this
      prenatal screening were very heterogeneous. We conclude that a standard policy
      regarding the prevention of vertical transmission of HBV is currently lacking in
      Flanders.

PMID- 9529669
TI  - Histological classification of chronic hepatitis.
AB  - The 1968 classification of chronic hepatitis distinguished cirrhotic and non
      cirrhotic stages, and classified the disease according to the histological degree
      of disease activity into chronic persistent and chronic aggressive (active)
      varieties. This seemed appropriate at a time when the aetiology of chronic
      hepatitis was unknown, and presumed to be auto-immune. Immunosuppressive
      treatment was reserved for more severe variant of the disease, thus validating
      the usefulness of the classification. Over the past thirty years, several
      aetiologies were discovered for chronic hepatitis: the hepatitis viruses B, D, C,
      and G, side-effects of several therapeutic drugs, and autoimmune hepatitis. This
      progress created a growing need for a new or adapted classification of chronic
      hepatitis, since different aetiologies require divergent therapeutic approaches.
      In 1994, proposals for a new classification of chronic hepatitis came from two
      international organizations: the International Association for the Study of the
      Liver and the World Congresses of Gastroenterology. The essence of the proposals
      includes: primary classification according to aetiology, and determination of
      disease severity (grading) and stage of progression (staging). Several
      semiquantitative scoring systems for histological grading and staging of liver
      biopsies from patients with chronic hepatitis are available. Semiquantitative
      scoring is useful in the evaluation of new treatment regimens, and in comparing
      pre- and posttreatment biopsies. It is not indicated in the routine reporting of
      liver biopsies.

PMID- 9529670
TI  - Magnetic resonance cholangiopancreatography (MRCP): a perspective on potential
      clinical applications.
AB  - The recent development of MRCP allowed the recognition of the potential role of
      Magnetic Resonance (MR) in pancreatobiliary imaging. The increasing interest on
      MRCP relies on its non invasiveness (there is no need for contrast media
      administration) and on the projectional display of the biliary and pancreatic
      ducts in a way similar to endoscopic retrograde cholangiopancreatography (ERCP)
      or percutaneous transhepatic cholangiography (PTC). In addition, it offers the
      opportunity for dynamic analysis of biliopancreatic ducts which is useful in the
      assessment of subtle ductal alterations. The future of this attractive technique
      will depend on the demonstration of its diagnostic accuracy and on its
      availability. This article discusses the potential role of MRCP in the evaluation
      of biliary tract and pancreatic duct diseases.

PMID- 9529671
TI  - Endoanal magnetic resonance imaging.
AB  - PURPOSE: To review the results of endoanal magnetic resonance imaging (MR) in
      patients with anal sphincter defects and anal fistulas. MATERIAL AND METHODS:
      Normal volunteers, patients with faecal incontinence, and patients with perianal
      fistulas were studied. Endoanal MRI was performed with a rigid, endoluminal anal
      coli with a diameter of 19 mm. An axial T2-weighted gradient echo and sagittal,
      coronal and radial T2-weighted turbo spin-echo sequence were performed. RESULTS:
      Normal anatomy. The most important finding was that the outer part of the anal
      sphincter complex is caudally the external sphincter, while the upper part is the
      puborectal muscle. This is in contrast to previous anatomical and surgical
      studies. Our findings concerning the internal sphincter and longitudinal muscle
      are not very different from previous studies. The internal sphincter is the inner
      part of the anal sphincter, surrounded by the intersphincteric space with the
      longitudinal layer. SPHINCTER DEFECTS: Especially the external sphincter is more
      clearly and consistently demonstrated with MRI than with endoanal sonography. In
      our experience so far, the results of endoanal sonography and MRI are
      approximately comparable for internal sphincter defects, but MRI is superior in
      the detection of external sphincter defects. PERIANAL FISTULAS: Our results of a
      study of endoanal sonography and endoanal MRI in perianal fistulas indicate
      preference for MRI especially in the classification of transsphincteric fistulas.
      The accurate identification of the external sphincter and the differentiation
      between scar tissue and a track with endoanal MRI are the major reasons for this
      preference. In another study was demonstrated that endoanal MRI was preferable to
      surface coil MRI. CONCLUSION: The introduction of endoanal MRI has been a major
      step in anal imaging. The multiplanar capacities and high inherent contrast
      facilitate the demonstration of the anal anatomy. Our preliminary results
      indicate superiority of endoanal MRI as compared to endoanal sonography,
      especially in the identification of external sphincter defects and the
      classification of perianal fistulas.

PMID- 9529672
TI  - Usefulness of 18FDG positron emission tomography in detection and follow-up of
      digestive cancers.
AB  - PET is a diagnostic method that creates high resolution, 3 dimensional
      tomographic images of the distribution of positron emitting radionuclides in the
      human body. Recent technological developments allow the use of whole-body PET
      devices in clinical oncology. 18FDG is a glucose analog transported and
      competitively used with glucose reflecting the increased glucose metabolism into
      malignant cells. Differential diagnosis between chronic pancreatitis and
      pancreatic cancer is already a well-documented indication. For initial staging of
      gastro-esophageal and colorectal tumours, results are preliminary but the
      clinical impact seems to be rather limited. At present, the major indication of
      FDG-PET is the detection and staging of colorectal cancer recurrences. FDG-PET
      allows the differentiation between scared tissue and tumour when structural
      imaging is often confusing. In the same time, the whole-body imaging capability
      provides unique information that can modify loco-regional and liver staging.
      Overall, FDG-PET affects the clinical management of 30 to 40% of these patients.
      Quantitative assessment of therapeutic response to chemotherapy regimen appears
      to be one of the most promising applications of FDG-PET. Since the most effective
      therapy of colorectal cancer are often surgical, the role of chemotherapy in
      colorectal cancer remains limited to adjuvant therapy and in advanced disease.
      However, FDG-PET could be of great value in assessing the response of oesophageal
      carcinomas to chemo-radio therapy, before surgery. In our experience, FDG-PET
      appears to be the first line diagnostic method in the detection and staging of
      colorectal recurrence and differential diagnosis of pancreatic tumour versus
      chronic pancreatitis.

PMID- 9529673
TI  - Present status and future prospects in abdominal organ transplantation.

PMID- 9529674
TI  - Xenotransplantation: a clinically achievable goal?

PMID- 9529675
TI  - Organ transplantation in children.

PMID- 9529676
TI  - Current status of pancreas transplantation for treatment of type I diabetes
      mellitus.
AB  - Pancreas transplantation is the only treatment of Type I diabetes that
      consistently establishes an insulin-independent, normoglycemic state. Currently
      long-term (> 1 year) insulin-independence is achieved in > 80% of recipients of
      pancreas grafts placed simultaneous with the kidney and > 70% in recipients of a
      pancreas after a kidney, and > 60% of non-uremic recipients of a pancreas alone.
      The penalty is immunosuppression, already obligatory for a kidney recipient, but
      the benefits are improvement in quality of life and the effect that perfect
      control of glycemia can have on secondary complications.

PMID- 9529677
TI  - Acute liver failure.

PMID- 9529678
TI  - Gastric involvement with Anisakis sp. larva in a Belgian patient after
      consumption of cod.
AB  - A case of acute episode of gastric anisakiasis in a patient, which was acquired
      through the consumption of infected cod meat and could be successfully resolved
      by endoscopic extraction, is described and discussed. This is the first report of
      cod as infection source as well as an authentic case of gastric anisakiasis in
      Belgium.

PMID- 9529679
TI  - Localized amyloid tumour of the duodenum : a case report.
AB  - Amyloid tumours in the gastrointestinal tract are rare. A case is presented of a
      localized amyloid tumour in the duodenum, which was removed by loop resection
      during ERCP.

PMID- 9529681
TI  - Lichen planus.
AB  - Lichen Planus is a relatively common inflammatory dermatosis of unknown origin.
      The present review summarizes the histological and clinical features of lichen
      planus and variants, including lichenoid drug reactions, are described. Possible
      mechanisms of pathogenesis of lichen planus are reviewed. The development of
      malignancy in association with lichen planus and the association with hepatitis
      are discussed. Treatment options for the more difficult manifestations of lichen
      planus are proposed.

PMID- 9529682
TI  - Mast cells in clinical dermatology.
AB  - Recent advances in cutaneous mast cell biology are briefly reviewed with special
      reference to our own studies on cultured human mast cells. Of note are the
      heterogeneity of mastocytosis, the important participation of mast cells in
      allergic inflammation by releasing cytokines and the inhibitory effect of
      histamine release from mast cells by phototherapy. It is also stressed that mast
      cells play a major role in tissue remodelling. These novel findings suggest that
      mast cells can no longer be regarded simply as cells that initiate immediate
      allergic reactions, but that they are responsible for various chronic
      inflammatory or immunological events through cytokine-dependent leucocyte
      recruitment. The regulation of mast cell activation should be a critical issue
      and, thus, a promising therapeutic approach in clinical dermatology.

PMID- 9529683
TI  - Dermal connective tissue metabolism in photoageing.
AB  - The term photoageing describes the clinical and histological cutaneous changes
      that are the consequence of repeated chronic sun exposures and are qualitatively
      different from those observed in chronological ageing. The connective tissue of
      the skin is composed mainly of collagen, glycosaminoglycans and elastin and,
      thus, alterations of these components in photoageing are briefly reviewed in the
      present article. Collagen changes in photoageing are partly explained by cross
      links as well as the unbalanced regulation of collagen production and breakdown.
      Some visible skin changes can be induced by the consequence of dermal
      glycosaminoglycans, because the total amount, as well as the composition of the
      main disaccharide units, is significantly altered in the exposed sites of both
      aged people and photoaged mice. As for the mechanism of solar elastosis,
      increased elastin mRNA levels resulting from transcriptional up-regulation of the
      gene have been reported. Taken together, all components of the dermal connective
      tissue are affected by chronic actinic damage; however, further in vitro
      investigation is required to unmask the exact events in photoageing. With regard
      to this, our novel three-dimensional culture system should be of great help
      because it mimics the in vivo condition by self producing the extracellular
      matrices.

PMID- 9529684
TI  - Hirsutes. I: Diagnosis.
AB  - Hirsutes, the coarse, androgen-dependent growth of hair in women, is a common
      problem faced by doctors. Whether a woman presents to a clinician or not depends
      on cultural and racial factors. The clinician must differentiate normal
      biological variation from cases of hirsutes. In the vast majority of cases,
      androgen excess is only found locally at the level of the hair follicle; that is,
      the hirsutism is idiopathic. Important causes of androgen excess, such as an
      ovarian tumour, need to be excluded. Part one describes the causes of hirsutism
      and how to differentiate them using history, examination and investigation.

PMID- 9529686
TI  - Melanoma: accuracy of clinical diagnosis.
AB  - Clinical diagnosis of melanoma can be difficult. A review of the accuracy of
      clinical diagnosis of melanoma, over a 12 month period, was undertaken at the
      Skin and Cancer Foundation Australia. The overall accuracy rate was 65.6% with
      seborrhoeic keratosis, melanocytic naevi and basal cell carcinoma the most common
      clinical misdiagnoses given to melanoma. Specialist doctors with more than 10
      years experience had a higher rate of correct diagnosis than trainee doctors with
      0-5 years experience.

PMID- 9529685
TI  - Long-term follow up of patients with toenail onychomycosis after treatment with
      terbinafine.
AB  - The long-term outcome of 111 patients treated with oral terbinafine for toenail
      onychomycosis with a novel treatment protocol was assessed a median of 138 weeks
      after entry into the trial. All but three patients had either one or two 12 week
      courses of terbinafine 250 mg daily. Of the 77 evaluable patients, 72.7% were
      still classified as responders (i.e. negative mycological culture and at least 3
      mm of new unaffected nail growth) on reassessment. The present study shows that a
      favourable long-term outcome can be achieved in patients who have been treated
      with at least one 12 week course of terbinafine.

PMID- 9529687
TI  - Epidemic cutaneous sporotrichosis: report of 16 cases in Queensland due to mouldy
      hay.
AB  - We report an epidemic of sporotrichosis in a south-east Queensland rural
      community. Sporotrichosis is a fungal infection due to the organism Sporothrix
      schenckii, typically presenting with cutaneous lesions. Sixteen cases of
      cutaneous sporotrichosis were seen over a 9 month period in the Darling Downs
      region of Queensland. All patients had had contact with a batch of mouldy hay
      presumed to be contaminated by Sporothrix schenckii. Nine of 16 patients were
      male; the youngest patient was aged 11 and the oldest was 67 years of age.
      Lymphocutaneous sporotrichosis was seen in 50% of patients; the rest demonstrated
      the fixed cutaneous form. No cases of disseminated cutaneous or systemic
      sporotrichosis were seen. One case demonstrated lymphangitis related to
      sporotrichosis. No apparent difference in the duration to diagnosis was
      demonstrated to exist between lymphocutaneous or fixed cutaneous types.

PMID- 9529688
TI  - Epidermolysis bullosa acquisita in childhood.
AB  - This case report of an 11-year-old girl describes a juvenile form of
      epidermolysis bullosa acquisita, an autoimmune disease of IgG antibodies to
      basement membrane type 7 collagen. Our case illustrates an unusually severe,
      acute inflammatory presentation of this condition with prominent mucosal and
      constitutional features requiring admission to a paediatric burns unit. The
      treatment consisted of supportive topical and systemic agents, prednisolone and
      dapsone. She responded to dapsone alone and the course of the illness was
      uneventful.

PMID- 9529689
TI  - Pellagra in a woman using alternative remedies.
AB  - A young woman presented with pellagra. Dietary intake of niacin was in excess of
      recommended guidelines. She had a low body mass index and was taking a number of
      alternative remedies. Resolution was rapid with oral nicotinic acid and
      discontinuation of the remedies.

PMID- 9529690
TI  - Hypertrophic lichen planus mimicking squamous cell carcinoma.
AB  - An 87-year-old female presented with a 3 month history of hyperkeratotic nodules
      on her left shin. An initial clinical and histological diagnosis of multiple
      squamous cell carcinomas on the left shin was made. Review of the biopsy,
      however, showed hypertrophic lichen planus with pseudoepitheliomatous
      hyperplasia. Typical lichen planus was seen affecting the oral mucosa, nails and
      skin elsewhere.

PMID- 9529691
TI  - Allergic contact dermatitis from azo dyes.
AB  - Contact allergy to textile dyes usually occurs with disperse dyes of the azo or
      anthraquinone groups. A case is reported of a woman with clinical features of
      contact allergy to coloured nylon stockings who had multiple sensitivities to
      dyes of different azo groups.

PMID- 9529692
TI  - Tips for a better local anaesthetic.
AB  - The expert use of local anaesthetics is simple and will greatly enhance patients'
      acceptance of office-based procedures. Correct equipment and techniques will
      enable all dermatologists to practise local anaesthesia as effectively and
      painlessly as possible. Suggested equipment varies according to the situation,
      but in general Luer-Lock syringes of the smallest volume and needles of the
      narrowest gauge and shortest length appropriate for the procedure are
      recommended. Making the anaesthetic agent less acidic will minimize the pain.
      Techniques to minimize pain involve careful explanation to the patient, slow
      injection of the anaesthetic and making use of the special anatomy of the region
      to be anaesthetized. The number of needle pricks should be kept to a minimum.
      Timing of the surgical procedure should take into account the delay in onset of
      anaesthesia for subcutaneously injected solution and the time for injected
      adrenaline to produce full vasoconstriction. Planned surgical incision lines
      drawn out precisely prior to the injection will avoid the problem of distortion
      caused by tissue expansion. Gloves and appropriate eye protection should be
      standard and needles and syringes must be disposed of correctly.

PMID- 9529693
TI  - A history of the institutions of Australian dermatology.

PMID- 9529694
TI  - Failure of fluoxetine to modify the skin-picking behaviour of Prader-Willi
      syndrome.

PMID- 9529695
TI  - Response to the article 'An organic refrigerant for cryosurgery: fact or
      fiction?'.

PMID- 9529697
TI  - Minimising vision impairment in the community.

PMID- 9529698
TI  - Working in Aboriginal controlled community health services.

PMID- 9529696
TI  - Generalized lichen nitidus in a child's response to cetirizine
      dihydrochloride/levamisol.

PMID- 9529699
TI  - Sudden loss of vision.
AB  - BACKGROUND: Sudden loss of vision is an ophthalmological emergency. OBJECTIVE:
      This article explains how history and examination, particularly ophthalmoscopy,
      will greatly assist the general practitioner to diagnose the cause. DISCUSSION:
      Vision loss may be transient or prolonged. It is important to consider whether
      the eye is painful or comfortable, inflamed or not. An accurate diagnosis will
      direct the emergency management, which frequently determines the prognosis for
      vision.

PMID- 9529700
TI  - Gradual loss of vision.
AB  - BACKGROUND: With the increasing age of our population many of the causes of
      vision loss are becoming more frequent. Not all gradual loss of vision can be
      considered non urgent and those patients requiring early attention are
      highlighted. OBJECTIVE: This article discusses the tools available to the general
      practitioner for the assessment of visual loss as well as the common causes.
      DISCUSSION: Advances in cataract surgery with improved visual outcome, minimally
      invasive surgery and a reduction in surgical risk have made this operation the
      commonest performed in Australia. Blindness from chronic open angle glaucoma and
      diabetes can be mostly prevented by early diagnosis and compliance with
      treatment. Age related macular degeneration apart from a small subgroup, is still
      largely untreatable.

PMID- 9529701
TI  - Prevention of visual loss. Screening in general practice.
AB  - BACKGROUND: Diseases such as primary open angle glaucoma, diabetes, strabismus
      and retinoblastoma have been found to have improved outcome by early
      investigations. Australian GPs are currently well placed to enhance their role in
      preventable blindness. OBJECTIVE: To identify key clinical target areas for the
      prevention of visual loss and discuss opportunities to address these in everyday
      general practice. DISCUSSION: Undertaking visual assessment in both children and
      adults can have benefits in reducing the incidence of preventable blindness in
      the community. Upskilling and having protocols to work to can enhance the GP's
      ability to offer this preventive service.

PMID- 9529702
TI  - Laser refractive surgery.
AB  - BACKGROUND: Refractive errors; myopia, hypermetropia and astigmatism, have
      traditionally been corrected by glasses and more recently contact lenses. For
      nearly 100 years surgical techniques to treat such disorders have also been
      developed. The latest of these are based upon the use of the excimer laser to
      ablate the corneal stroma either directly under the corneal epithelium (surface
      PRK) or under a flap of superficial stroma (LASIK). OBJECTIVE: To look at the
      development of laser refractive surgery and to put this in the context of
      appropriate and inappropriate indications for usage. DISCUSSION: While the
      development of such techniques has revolutionised the field of refractive surgery
      unrealistic expectations with regard to the outcome of such procedures may have
      been raised in recent advertising by some ophthalmologists and laser centres. The
      most important influence on the refractive outcome of such procedures is the pre
      operative refraction. The best outcomes are seen with treating low degrees of
      myopia and/or astigmatism. Outcomes for treating high degrees of myopia or
      astigmatism are often disappointing. The treatment of hypermetropia remains
      experimental.

PMID- 9529703
TI  - Support is available. Assisting patients with severe sight loss.
AB  - BACKGROUND: There are a large number of free services for people who are blind or
      vision impaired. OBJECTIVE: As the population of Australia ages, it is becoming
      increasingly important that general practitioners have an understanding of the
      range of services available to people with disabilities. DISCUSSION: General
      practitioners are well placed to provide information to patients about these
      services. Appropriate support from blindness agencies can enable people who are
      blind or vision impaired to live independent lives.

PMID- 9529704
TI  - The fragile X syndrome.
AB  - Fragile X syndrome (FXS) is the most common cause known of inherited
      developmental disability. New and widely available techniques in DNA analysis
      allow both affected individuals and carriers to be tested from a simple blood
      sample. It is now recognised that a wide range of clinical severity occurs in
      both sexes. Specific treatment and interventional strategies are now available
      and of great benefit to individuals, families and carers. Genetic counselling
      allows families to make informed decisions. General practitioners can play a
      central role in detection and management of this syndrome.

PMID- 9529705
TI  - Vigilance and flexibility. Pathways to a diagnosis.

PMID- 9529707
TI  - Death certification by doctors in non-metropolitan Victoria.
AB  - OBJECTIVE: To examine the completeness and accuracy of death certification by
      general practitioners, specialists and resident medical officers (RMOs) in non
      metropolitan Victoria. DESIGN: An examination of the death certificates written
      by a representative sample of community and hospital doctors and comparison with
      the clinical history. SETTING: The Ballarat statistical district. RESULTS:
      Eighteen percent of the death certificates at initial assessment, were
      unsatisfactory (the percentage for those written by RMOs were significantly
      higher). After review of the clinical record, 27% of certificates were found to
      inaccurately represent the cause of death, (again the percentage for RMOs was
      higher) Eighteen percent of certificates required a change of code. CONCLUSION:
      Monitoring the health of the public relies in part on information gained from
      death certificates. It is thus of concern that such a high percentage of death
      certificates are inaccurate to the extent that they are incorrectly coded.
      Consideration should be given to new educational initiatives and to the promotion
      of the existing toll free telephone advice service to doctors.

PMID- 9529708
TI  - Asthma diagnosis by spirometry. Sensitive or specific?
AB  - Spirometry is the recommended first-line investigation for diagnosing asthma,
      with greater than 15% improvement in FEV1 considered diagnostic. However,
      evidence suggests a majority of asthmatics may go undetected at 15%, thus a lower
      diagnostic value may be preferred.

PMID- 9529706
TI  - Defining the question. A key and neglected step in the research process.
AB  - This paper argues that a good question lies at the heart of the research process,
      and should possess four attributes: clarity, relevance, and be both worth
      answering and answerable. That is, it should lead to something that can be
      defined and measured.

PMID- 9529709
TI  - Ocular first aid.

PMID- 9529710
TI  - Headache and hydrocephalus.

PMID- 9529711
TI  - A non healing skin lesion.

PMID- 9529712
TI  - Practice tip. Incision and curettage of chalazion.

PMID- 9529713
TI  - Difficulties in documenting immunisation status in general practice.

PMID- 9529714
TI  - Integrated management of childhood illness by outpatient health workers:
      technical basis and overview. The WHO Working Group on Guidelines for Integrated
      Management of the Sick Child.
AB  - This article describes the technical basis for the guidelines for the integrated
      management of childhood illness (IMCI), which are presented in the WHO/UNICEF
      training course on IMCI for outpatient health workers at first-level health
      facilities in developing countries. These guidelines include the most important
      case management and preventive interventions against the leading causes of
      childhood mortality--pneumonia, diarrhoea, malaria, measles and malnutrition. The
      training course enables health workers who use the guidelines to make correct
      decisions in the management of sick children. The guidelines have been refined
      through research studies and field-testing in the Gambia, Ethiopia, Kenya, and
      United Republic of Tanzania, as well as studies on clinical signs in the
      detection of anaemia and malnutrition. These studies, and two others from Uganda
      and Bangladesh, are presented in this Supplement to the Bulletin of the World
      Health Organization.

PMID- 9529715
TI  - Evaluation of an algorithm for the integrated management of childhood illness in
      an area with seasonal malaria in the Gambia.
AB  - Most of the 12.4 million deaths occurring every year among under-5-year-olds in
      developing countries could be prevented by the application of simple treatment
      strategies. So that health professionals who have had limited training can
      identify and classify the common childhood diseases, WHO developed a treatment
      algorithm (the Integrated Management of Childhood Illness (IMCI) or Sick Child
      algorithm), a prototype of which was tested in 440 Gambian children aged between
      2 months and 5 years. The children were first assessed by a trained field worker
      using the algorithm, and then by a paediatrician whose clinical diagnosis was
      supported by laboratory investigations and, when indicated, a chest X-ray.
      Compared with the paediatrician's diagnosis, the sensitivity and specificity of
      the draft IMCI algorithm were, respectively, 81% and 89% for the detection of
      pneumonia, 67% and 96% for dehydration, 87% and 8% for malaria parasitaemia (any
      level), 100% and 9% for malaria parasitaemia (above 5000 parasites/microliter),
      100% and 99% for measles, 31% and 97% for otitis media, and 89% and 90% for
      malnutrition. Among the children admitted by the physician, 45% had been
      recommended for admission by the algorithm. Intermittent fever, chills and sweats
      did not help in discriminating between malaria and non-malarious fevers;
      shivering or shaking of the body had a sensitivity of only 35%. While the
      algorithm dealt with the majority of presenting complaints, the most common
      problems not addressed by the chart were skin rashes (21%), mouth problems (8%),
      and eye problems (6%). The draft IMCI algorithm proved to be effective in the
      diagnosis of pneumonia, gastroenteritis, measles and malnutrition, but not
      malaria where its use without microscopy would result in considerable over
      treatment, especially in a low transmission area or during a low transmission
      season in countries with seasonal malaria. The current algorithm would benefit
      from expansion to cover management of localized infections as well as skin, mouth
      and eye problems.

PMID- 9529717
TI  - Performance of health workers after training in integrated management of
      childhood illness in Gondar, Ethiopia.
AB  - The performance of six primary health workers was evaluated after following a 9
      day training course on integrated management of childhood illness (IMCI). The
      participants were selected from three primary health centres in the Gondar
      District, Ethiopia, and the course was focused on assessment, classification, and
      treatment of sick children (aged 2 months to 5 years) and on counselling of their
      mothers. Immediately following this training, a 3-week study was conducted in the
      primary health centres to determine how well these workers performed in
      assessing, classifying and treating the children and in counselling the mothers.
      A total of 449 sick children who presented at the three primary health centres
      during the study period were evaluated. Most of the complaints (87%) volunteered
      by the mothers (fever, cough, diarrhoea, and ear problems) were covered by the
      IMCI charts. The assessment of commonly seen signs (tachypnoea or ear pain) or
      easily identifiable signs (slow return after skin pinch, wasting, or pedal
      oedema) was good, with sensitivities of 67-91%, whereas the assessment of
      uncommonly seen signs (dry mouth, corneal clouding) or less easily quantifiable
      signs (eyelid pallor, absence of tears) had a fair or poor sensitivity of 20-45%.
      The classification of pneumonia, diarrhoea with signs of dehydration, and
      malnutrition showed sensitivities of 88%, 76%, and 85% and specificities of 87%,
      98%, and 96%, respectively. However, the classification of febrile illnesses had
      a sensitivity of only 39% due to problems in using the draft algorithm in areas
      with a mixture of high, low, and no malaria risk, and due to confusion between
      axillary and rectal temperature thresholds. Of 39 children classified as having
      severe disease, 9 were misclassified, mostly by one nurse. Treatment of patients
      improved over the three weeks of observation, their completeness increasing from
      69% to 88%. Health workers usually communicated appropriate advice to the mother.
      They learned to use checking questions but failed to adequately solve problems in
      the majority of cases. The mother's counselling card, which summarized
      recommendations on feeding and home fluids, and advice on when to return, was
      widely used to aid communication. The time taken to perform the complete
      management of children did not change significantly (20 to 19 minutes) during the
      study. Lessons from our findings have been incorporated into an improved version
      of the IMCI charts.

PMID- 9529716
TI  - Evaluation of an algorithm for integrated management of childhood illness in an
      area of Kenya with high malaria transmission.
AB  - In 1993, the World Health Organization completed the development of a draft
      algorithm for the integrated management of childhood illness (IMCI), which deals
      with acute respiratory infections, diarrhoea, malaria, measles, ear infections,
      malnutrition, and immunization status. The present study compares the performance
      of a minimally trained health worker to make a correct diagnosis using the draft
      IMCI algorithm with that of a fully trained paediatrician who had laboratory and
      radiological support. During the 14-month study period, 1795 children aged
      between 2 months and 5 years were enrolled from the outpatient paediatric clinic
      of Siaya District Hospital in western Kenya; 48% were female and the median age
      was 13 months. Fever, cough and diarrhoea were the most common chief complaints
      presented by 907 (51%), 395 (22%), and 199 (11%) of the children, respectively;
      86% of the chief complaints were directly addressed by the IMCI algorithm. A
      total of 1210 children (67%) had Plasmodium falciparum infection and 1432 (80%)
      met the WHO definition for anaemia (haemoglobin < 11 g/dl). The sensitivities and
      specificities for classification of illness by the health worker using the IMCI
      algorithm compared to diagnosis by the physician were: pneumonia (97%
      sensitivity, 49% specificity); dehydration in children with diarrhoea (51%, 98%);
      malaria (100%, 0%); ear problem (98%, 2%); nutritional status (96%, 66%); and
      need for referral (42%, 94%). Detection of fever by laying a hand on the forehead
      was both sensitive and specific (91%, 77%). There was substantial clinical
      overlap between pneumonia and malaria (n = 895), and between malaria and
      malnutrition (n = 811). Based on the initial analysis of these data, some changes
      were made in the IMCI algorithm. This study provides important technical
      validation of the IMCI algorithm, but the performance of health workers should be
      monitored during the early part of their IMCI training.

PMID- 9529718
TI  - Integrated management of childhood illness: field test of the WHO/UNICEF training
      course in Arusha, United Republic of Tanzania. WHO Division of Child Health and
      Development & WHO Regional Office for Africa.
AB  - The 11-day training course on integrated management of childhood illness was
      field tested with three types of first-level facility health workers: medical
      assistants, rural medical aides, and MCH (maternal and child health) aides. The
      objective of the field test was to determine whether the materials were effective
      in preparing participants to manage correctly sick children and to suggest
      improvements in the course materials and teaching procedures. The course combined
      classroom work and daily inpatient and outpatient clinical sessions. Each
      participant individually examined 9-10 inpatients and managed more than 30 sick
      children as outpatients. Individual feedback from facilitators during clinical
      practice and module work, combined with data collection documenting the adequacy
      of the assessment, classification, treatment and counselling carried out by the
      participants, allowed an assessment of the participants' mastery of key clinical
      skills. Although some participants had difficulty in reading the modules in
      English, all three groups overall were able to assess, classify, and treat most
      sick children by the end of the course, and most of them were able to provide
      adequate counselling. Specific improvements were suggested and subsequently
      incorporated into the guidelines and training materials.

PMID- 9529720
TI  - The integrated management of childhood illness in western Uganda.
AB  - Bringing together various disease-specific guidelines for sick children, WHO and
      UNICEF have developed an Integrated Management of Childhood Illness (IMCI)
      algorithm, one component of which (assess and classify) was tested in the
      outpatient department of a rural district hospital in western Uganda. Children
      aged 2-59 months were seen first by a Ugandan medical assistant trained in IMCI,
      and then evaluated by a medical officer. Sensitivity, specificity and positive
      predictive values were determined by comparing the IMCI classifications with a
      reference standard based on the medical officers' diagnoses and laboratory tests.
      Of the 1226 children seen, 69% were classified into more than one symptom
      category, 7% were not classified in any symptom category, 8% had a danger sign,
      and 16% were classified into a severe category, for which the IMCI approach
      recommended urgent hospital referral. Specificity for most classifications was
      good, though sensitivity and positive predictive values were variable. We
      conclude that the IMCI algorithm is an important advance in the primary care of
      sick children in developing countries.

PMID- 9529719
TI  - Identifying sick children requiring referral to hospital in Bangladesh.
AB  - The object of this study was to evaluate and improve the guidelines for the
      Integrated Management of Childhood Illness (IMCI) with respect to identifying
      young infants and children requiring referral to hospital in an area of low
      malaria prevalence. A total of 234 young infants (aged 1 week to 2 months) and
      668 children (aged 2 months to 5 years) were prospectively sampled from patients
      presenting at a children's hospital in Dhaka, Bangladesh. The study
      paediatricians obtained a standardized history and carried out a physical
      examination, including items in the IMCI guidelines developed by WHO and UNICEF.
      The paediatricians made a provisional diagnosis and judged whether each patient
      needed hospital admission. Using the paediatrician's assessment of a need for
      admission as the standard, the sensitivity and specificity of the current and
      modified IMCI guidelines for correctly referring patients to hospital were
      examined. The IMCI's sensitivity for a paediatrician's assessment in favour of
      hospital admission was 84% (95% confidence interval (CI): 75-90) for young
      infants and 86% (95% CI: 81-90) for children, and the specificity was,
      respectively, 54% (95% CI: 45-63) and 64% (95% CI: 59-69). One fourth or more in
      each group had a provisional diagnosis of pneumonia, and the IMCI's specificity
      was increased without lowering sensitivity by modifying the respiratory signs
      calling for referral. These results show that the IMCI has good sensitivity for
      correctly referring young infants and children requiring hospital admission in a
      developing country setting with a low prevalence of malaria. The guidelines'
      moderate specificity will result in considerable over-referral of patients not
      needing admission, thereby decreasing opportunities for successful treatment of
      patients at first-level health facilities. The impact of the IMCI guidelines on
      children's health and the health care system must be judged in the light of
      current treatment practices, health outcomes and referral patterns.

PMID- 9529721
TI  - Assessment of potential indicators for protein-energy malnutrition in the
      algorithm for integrated management of childhood illness.
AB  - Potential indicators were assessed for the two classifications of protein-energy
      malnutrition in the guidelines for integrated management of childhood illness:
      severe malnutrition, which requires immediate referral to hospital, and very low
      weight, which calls for feeding assessment, nutritional counselling and follow
      up. Children aged < 2 years require feeding assessment and counselling as a
      preventive intervention. For severe malnutrition, we examined 1202 children
      admitted to a Kenyan hospital for any association of the indicators with
      mortality within one month. Bipedal oedema indicating kwashiorkor, and two
      marasmus indicators (visible severe wasting and weight-for-height (WFH) Z-score
      of < -3) were associated with a significantly increased mortality risk (odds
      ratios, 3.1-3.9). Very low weight-for-age (WFA) (Z-score of < -4.4) was not
      associated with an increased risk of mortality. Because first-level health
      facilities generally lack length-boards, bipedal oedema and visible severe
      wasting were chosen as indicators of severe malnutrition. To assess potential WFA
      thresholds for the very low weight classification, our primary source of data
      came from 1785 Kenyan outpatient children, but we also examined data from surveys
      in Nepal, Bolivia, and Togo. We examined the performance of WFA at various
      thresholds to identify children with low WFH and, for children aged < or = 2
      years, low height-for-age (HFA). Use of a WFA threshold Z-score of < -2
      identified a considerable proportion of children (from 13% in Bolivia to 68% in
      Nepal) which, in most settings, would pose an enormous burden on the health
      facility. Among ill children in Kenya, a threshold WFA Z-score of < -3 had a
      sensitivity of 89-100% to detect children with WFH Z-scores of < -3, and, with an
      identification rate of 9%, would avoid overburdening the clinics. Potential
      modifications include use of a more restrictive cut-off in countries with high
      rates of stunting, or the elimination of the WFA screen in order to concentrate
      efforts on intervention for all children below the 2-year age cut-off. Key issues
      in every country include the capacity to provide counselling for many children
      and linkage to nutritional improvement programmes in the community.

PMID- 9529722
TI  - Clinical signs for the recognition of children with moderate or severe anaemia in
      western Kenya.
AB  - Optimal treatment of Plasmodium falciparum-related paediatric anaemia can result
      in improved haematological recovery and survival. Clinical predictors are needed
      to identify children with anaemia in settings where laboratory measurements are
      not available. The use of conjunctival (eyelid), palmar, nailbed, and tongue
      pallor to detect children with moderate anaemia (haemoglobin, 5.0-7.9 g/dl) or
      severe anaemia (haemoglobin, < 5.0 g/dl) was evaluated among children seen at an
      outpatient and inpatient setting in a hospital in western Kenya. Severe nailbed
      or severe palmar pallor had the highest sensitivity (62% and 60%, resp.),
      compared with severe conjunctival pallor (sensitivity = 31%), to detect children
      with severe anaemia in the outpatient setting. Children with moderate anaemia
      were best identified by the presence of nailbed or palmar pallor (sensitivity =
      90% for both signs), compared with conjunctival pallor (sensitivity = 81%).
      Clinical signs of respiratory distress, in addition to the presence of severe
      pallor, did not increase the recognition of children requiring hospitalization
      for severe anaemia. Among inpatients, the sensitivity of severe nailbed pallor
      (59%) was highest for detecting children with severe anaemia, although the
      sensitivity of severe conjunctival pallor and severe palmar pallor was the same
      (53% for both signs). Presence of conjunctival pallor (sensitivity = 74%) was
      similar in sensitivity to both nailbed and palmar pallor (70% for both signs)
      among children with moderate anaemia. The sensitivity of tongue pallor was low
      among all children evaluated. Low haemoglobin levels were significantly
      associated with the likelihood of being smear-positive for P. falciparum. This
      study demonstrates that clinical criteria can be used to identify children with
      moderate and severe anaemia, thus enabling implementation of treatment
      algorithms. Children aged < 36 months who live in an area with P. falciparum
      malaria should receive treatment with an effective antimalarial drug if they have
      pallor.

PMID- 9529723
TI  - Evaluation of clinical signs to diagnose anaemia in Uganda and Bangladesh, in
      areas with and without malaria.
AB  - The object of this study was to assess the ability of pallor and other clinical
      signs, including those in the Integrated Management of Childhood Illness (IMCI)
      guidelines developed by WHO and UNICEF, to identify severe anaemia and some
      anaemia in developing country settings with and without malaria. A total of 1226
      and 668 children aged 2 months to 5 years were prospectively sampled from
      patients presenting at, respectively, a district hospital in rural Uganda and a
      children's hospital in Dhaka, Bangladesh. The study physicians obtained a
      standardized history and carried out a physical examination that included pallor,
      signs of respiratory distress, and the remaining IMCI referral signs. The
      haematocrit or haemoglobin level was determined in all children with conjunctival
      or palmar pallor, and in a sample of the rest. Children with a blood level
      measurement and assessment of pallor at both sites were included in the anaemia
      analysis. Using the haematocrit or haemoglobin level as the reference standard,
      the correctness of assessments using severe and some pallor and other clinical
      signs in classifying severe and some anaemia was determined. While the full IMCI
      process would have referred most of the children in Uganda and nearly all the
      children in Bangladesh with severe anaemia to hospital, few would have received a
      diagnosis of severe anaemia. Severe palmar and conjunctival pallor, individually
      and together, had 10-50% sensitivity and 99% specificity for severe anaemia; the
      addition of grunting increased the sensitivity to 37-80% while maintaining a
      reasonable positive predictive value. Palmar pallor did not work as well as
      conjunctival pallor in Bangladesh for the detection for severe or some anaemia.
      Combining "conjunctival or palmar pallor" detected 71-87% of moderate anaemia and
      half or more of mild anaemia. About half the children with no anaemia were
      incorrectly classified as having "moderate or mild" anaemia. Anaemia was more
      easily diagnosed in Uganda in children with malaria. Our results show that simple
      clinical signs can correctly classify the anaemia status of most children.
      Grunting may serve as a useful adjunct to pallor in the diagnosis of severe
      anaemia. Conjunctival pallor should be added to the IMCI anaemia box, or the
      guidelines need to be adapted in regions where palmar pallor may not readily be
      detected.

PMID- 9529725
TI  - Integrated management of childhood illness: conclusions. WHO Division of Child
      Health and Development.
AB  - The studies presented in this Supplement of the Bulletin of the World Health
      Organization have helped to improve the guidelines for integrated management of
      childhood illness (IMCI) and the WHO/UNICEF training course for teaching these
      guidelines to health workers in first-level health facilities. The findings of
      these studies and the lessons learned from early use of the training course in
      selected countries are being used to guide the adaptation of these guidelines to
      particular country circumstances. A broader IMCI strategy has been defined and is
      currently being implemented. The objectives of this strategy are to reduce child
      morbidity and mortality in developing countries, and to enhance child growth and
      development. IMCI activities in countries are therefore organized to improve
      health workers' skills, as described in the articles in this Supplement, improve
      the health system, and improve family and community practices. This concluding
      article on the IMCI guidelines draws together the results of field studies on
      their effectiveness, and identifies key issues that need to be addressed. It also
      describes the process for adapting the guidelines to specific country situations,
      and presents the broader IMCI strategy and the status of its implementation in
      several countries (as of May 1997).

PMID- 9529724
TI  - Pallor as a clinical sign of severe anaemia in children: an investigation in the
      Gambia.
AB  - Anaemia associated with malaria is a major public health problem in African
      countries. Since most primary health facilities have to rely on physical signs
      and not laboratory tests to detect anaemic patients who need referral for blood
      transfusion, we have assessed the reliability of simple clinical signs to predict
      severe anaemia. A trained field assistant examined 368 children admitted to a
      tertiary care hospital, assessing the pallor of their eyelids (conjunctiva),
      palms and nailbeds, counting the respiratory rate, and looking for signs of
      respiratory distress. After the children's admission, their packed cell volume
      (PCV) was measured, and the need for transfusion and the outcomes were noted. A
      second observer examined 173 of these children so that interobserver variability
      in the detection of clinical signs could be assessed. A total of 27% of the 368
      children had a PCV of < 15%. In a multiple regression analysis, definite pallor
      of the conjunctiva, definite pallor of the palms, and a "sick" appearance of the
      child were identified as independent significant predictors of a PCV of < 15%.
      The best predictor was a combination of definite pallor of the conjunctiva and
      pallor of the palms, with a sensitivity of 80% and a specificity of 85%.
      Inclusion of signs of respiratory distress did not improve the prediction. Pallor
      was a reproducible sign (weighted kappa statistic for the comparison between two
      observers: kappa = 0.6 for conjunctival pallor). We conclude that pallor can be
      used as a sign for referring children who may require blood transfusion.

PMID- 9529726
TI  - Prison suicide: a special issue.

PMID- 9529727
TI  - Befriending in prisons.

PMID- 9529728
TI  - Jail suicide and the need for debriefing.
AB  - Although first introduced more than 15 years ago, Critical Incident Stress
      Debriefing (CISD) has not been frequently utilized within the correctional
      community. As a structured protocol designed to prevent or mitigate traumatic
      stress, CISD has two main goals: (1) to lessen the impact of distressing critical
      incidents on the personnel exposed to them; (2) to accelerate recovery from those
      events before harmful stress reactions have a chance to damage the performance,
      careers, health, and families of personnel responding to emergencies. The need
      for debriefing remains acute. Whenever I conduct a jail-suicide prevention
      training seminar and explain the importance of the CISD process, correctional
      officers invariably approach me at the end of the workshop and begin to explain
      their experience with an inmate's suicide. Their voices are always characterized
      by frustration. This is one officer's story.

PMID- 9529729
TI  - Suicide in Greek prisons: 1977 to 1996.
AB  - Data obtained from the records of the Greek Ministry of Justice revealed that
      there were 457 deaths in the Greek prison system (which includes prisons, mental
      hospitals and other general hospitals) over the past 20 years. Of these deaths,
      93 were recorded as suicides--an average of 4.65 suicides per year or 112 per
      100,000 inmates classified as convinced, on remand or hospitalized. The suicide
      rates fluctuated widely, from a low rate 32.3 in 1982 to the incredibly high rate
      of 390.8 in 1979 (11 total suicides, 10 of which occurred in prison hospitals).
      The present study, the first of its kind in Greece, was based solely on
      unpublished prison data, which revealed defects in recording (e.g., 11% of the
      deaths recorded by the correctional administration remained without specification
      of cause in the years 1977 through 1996; social and penal demographic data of the
      inmates who committed suicide were kept unsystematically; detailed information on
      the circumstances of suicide was not always available, etc.). Despite a
      noticeable decrease in the suicide rate in the years 1995 and 1996, the limited
      data suggest that the suicide rate in the Greek prison system has basically
      remained stable over the past 20 years.

PMID- 9529730
TI  - Inmate suicides in the Correctional Service of Canada.
AB  - This article presents descriptive statistics on the 66 suicides occurring in
      federal institutions in Canada over a 4-year period. Criminological and
      institutional factors of those who committed suicide included lengthy involvement
      in the criminal justice system, a greater likelihood of being incarcerated for
      robbery or murder, and involvement in institutional incidents of a serious
      nature. In addition, 62% of the inmates who committed suicide had been
      transferred from other institutions within 6 months prior to suicide, though 59%
      evidenced no indicators of suicidal intent and 44% were not considered to be
      depressed at the time of suicide. Family problems (29%) were the most commonly
      hypothesized motivating factor in the suicides, followed by denial of a request
      for appeal, parole, or transfer (26%), fear of other inmates (24%), and substance
      abuse problems (21%). Current and planned suicide prevention and intervention
      strategies of the Correctional Service of Canada are discussed in the context of
      these findings.

PMID- 9529731
TI  - Suicide prevention in New South Wales Correctional Centres.
AB  - The New South Wales Department of Corrective Services has introduced a number of
      suicide prevention measures in order to deal with the problem of inmate suicides.
      This article describes the measures. The article also shows that the
      characteristics of the incarcerated population differ greatly from those in the
      community. Findings from the self-harm database 1991-1995 show that,
      nevertheless, there are some unique characteristics of the group of self-harmers
      and fatal self-harmers. These findings are discussed in relation to the
      preventive measures that are introduced in the NSW correctional centers.

PMID- 9529732
TI  - Prevention of suicides in Penal Institutions in The Netherlands.
AB  - As in other countries, suicides are a matter of great concern in The Netherlands.
      This article addresses suicide-prevention measures in prisons in The Netherlands.
      It focuses primarily on screening, monitoring, incapacitation, psychological
      support, and transferal to specialized institutions. In addition, it asks which
      practices are common, which can be improved, and the limitations of certain
      strategies. Relatively speaking, The Netherlands does not appear to be doing too
      badly in terms of preventive measures, although there is room for improvement.

PMID- 9529733
TI  - A solution to the problem of jail suicide.
AB  - Suicide in local jail facilities can be reduced through interagency cooperation
      and the implementation of core services. In 1985, the State of New York
      implemented a comprehensive suicide prevention program within its upstate local
      jail facilities. The program utilized key coordination strategies and risk
      management service components. It addressed not only the immediate needs of
      inmates with high-risk profiles, but also focused on the impact of the stressful
      jail experience on this already vulnerable population. Despite a nearly 100%
      increase in the jail population, there has been more than a 150% decrease in jail
      suicides since program implementation.

PMID- 9529734
TI  - Prison suicide--politics and prevention: a view from Ireland.
AB  - The pattern of suicide in Ireland broadly matches that in various neighbouring
      countries, with the prevalence among males being significantly greater than among
      women. Over recent years there has been a significant increase in suicide among
      young men. Similarly, prison suicide patterns mirror those in neighbouring
      jurisdictions, with a marked increase in prison suicides occurring over the last
      10 years. Media interest in prison suicide is grossly disproportionate to its
      frequency. Existing prevention policies based on the identification of
      individuals at risk would appear to have failed, and it is argued that it would
      be more productive--albeit with significant difficulty--to re-orient prevention
      strategies towards identifying and remedying risk factors in the overall prison
      environment as opposed to identifying particular individuals.

PMID- 9529736
TI  - Successful ageing: an ideal developing countries should aim for.

PMID- 9529735
TI  - Lung carcinoma presenting as multiple cystic lesions in the brain.
AB  - Eighty percent of brain metastases occur after the diagnosis of cancer has been
      established. A smaller number of cases are diagnosed synchronously with the
      primary site of malignancy. The majority of metastatic brain tumors present as
      small, well circumscribed densely enhancing masses with surrounding vasogenic
      edema. Cystic lesions are less common and when present raise the possibility of
      other disease processes affecting the brain. We report a case of cystic brain
      metastasis preceding the diagnosis of lung cancer in a patient with no systemic
      manifestations of malignancy, emphasizing the importance of clinical suspicion
      and histologic confirmation in determining treatment and predicting outcome.

PMID- 9529737
TI  - Elderly patients should receive all forms of medical treatment: a philosophical
      argument.
AB  - The use of old age as a criterion for rationing in medicine seems initially
      appealing. This is because many of the criteria currently being used for deciding
      the distribution of funds depend on subjective judgements. Age, however, is
      objective and therefore negates the need for value judgements. It has been
      suggested that justice and fairness require that limited resources be directed at
      young patients, who have not had a chance to live their lives, rather than at
      elderly patients who have already lived most of theirs. It is the purpose of this
      article to bring forth evidence that elderly patients should be accorded medical
      treatment on equal basis as younger patients and that policies which deny elderly
      people treatment on the sole grounds of age, are both unfair and discriminatory
      and should therefore be resisted.

PMID- 9529738
TI  - Ageing and poverty in rural Kenya: community perception.
AB  - Poverty is widespread among rural African elderly and associated with poor health
      and unsatisfactory access to health care. The purpose of this study was to
      determine community perception of the poorest in a community in rural Kenya, more
      specifically to identify factors considered by community members as associated
      with poverty in their midst. There is need to protect the aged members of the
      society from payment for health care and to include them in decision-making
      process. This study was undertaken in seven sites in Kisumu and Homa Bay
      districts in western Kenya where the Bamako Initiative was first launched, in
      1987, calling on UNICEF and WHO to help accelerate the implementation of primary
      health care at district level, giving priority to women and children. Two
      household interview baseline surveys comprising 210 and 87 households,
      respectively, corroborated by the more qualitative approaches of participatory
      rural appraisal (PRA) and focus group discussions were conducted. This article
      analyses the importance of ageing as perceived by the communities as a factor
      associated with poverty.

PMID- 9529739
TI  - Aetiology and implications of domestic injuries in the elderly.
AB  - This study was conducted in ten major city hospitals and twelve city council
      health clinics in Nairobi. Hospital records covering the period 1986 to 1990 were
      reviewed. Information on age, sex, occupation, type and cause of injury, the
      management and outcome of treatment was extracted from the records. This article
      focuses on the elderly, aged 55 years and above. The results indicate that falls
      inside the house accounted for most (69%) of the injuries. This was followed by
      accidental cuts (27%) and injuries resulting from domestic violence (26%). The
      main types of injuries recorded were open wounds (56%), followed by head injuries
      (24%) and fractures (21%). Most of the injuries (more than 63%) occurred in the
      low income areas (mainly Mathare and Eastlands). These injuries have implications
      on care for the elderly and on the cost to the individual, the health facilities
      and the nation. The results indicate that domestic injuries are a common
      occurrence among the elderly and there is need to focus on prevention and cost
      effective case management strategies.

PMID- 9529740
TI  - An overview on management of the traumatised elderly patient.
AB  - The elderly are predisposed to injuries due to consequences of ageing and
      presence of disease process commonly seen in the old people. Age-related
      deterioration of senses such as decrease in hearing capacity, presbyopia, changes
      in co-ordination, balance, motor strength and postural stability render the
      elderly vulnerable to environmental hazards. Diseases such as dementia,
      congestive cardiac failure, postural hypotension, osteoporosis and arthritis
      further contribute to compound problems of the elderly. Age and chronic factors
      further blunt the reserves to enable an elderly individual meet the demands of
      trauma. The challenge to the clinician is to be aware of the subtle changes and
      deviation from the norm that may suggest development of complications. With
      careful attention and appropriate physiological support the elderly patient has a
      good chance of survival. The primary condition must be assessed, necrotic tissues
      must be debrided by thorough surgical toileting, pus must be drained, wounds
      sutured and fractures must be set while cardiopulmonary activity must be
      monitored accurately. The patient should be re-assured, kept warm and adequate
      analgesia given to relieve pain. Intravascular volume and composition of
      extracellular fluid must be maintained. Nutritional support should be provided in
      amounts needed to meet the higher demands of trauma and preferably by oral
      feeding. Above all multidisciplinary approach to the traumatised elderly is
      mandatory involving surgeons, physicians, physiotherapists and other paramedical
      staff and relatives.

PMID- 9529741
TI  - Ageing and nutritional needs.
AB  - Nutrition is an important aspect of healthful behaviour and a major component of
      general wellbeing of individuals throughout their life cycle. While the ageing
      process compromises the body's ability to obtain nutrients from food, nutrition
      at the same time affects how people age. This article reviews the nutritional
      needs of the elderly people, from the age of 51 years and above, and highlights
      factors that can influence their nutritional status. The article concentrates on
      this age group, since the recommended nutritional requirements are stated from
      this age and above.

PMID- 9529742
TI  - Osteoporosis and the role of imaging in its evaluation.
AB  - Osteoporosis has been recognised as a major cause of morbidity and mortality in
      the elderly population due to the increased risk of fractures. Imaging modalities
      can recognise the presence of osteoporosis thus alerting the clinician. Detection
      of complications which exist may also be noted. However there is increasing
      reliance on imaging modalities which quantify the severity of osteoporosis. Such
      densitometric studies can conveniently group patients and provide a rational
      guide to the introduction of prophylactic and therapeutic interventions.

PMID- 9529743
TI  - Health and the elderly in developing countries with special reference to sub
      Saharan Africa.
AB  - The numbers of elderly people in sub-Saharan Africa are growing rapidly with
      increasing life expectancy while at the same time the proportions of children in
      the populations are declining. The number of people 80 years and above increased
      tenfold in large parts of Africa since the 1950's, and the number of widows is
      growing fast. All this has several implications, including erosion of the social
      support by extended families and a dramatic change in the disease pattern. There
      will be increasing rates of cancer, liver cirrhosis, kidney failure, eye disease,
      osteoarthrosis, diabetes, mental illness and chronic degenerative illnesses such
      as cardiovascular disease. Multiple illness and permanent disability will become
      more common. African health care systems are ill-prepared for this transition,
      and social security for the elderly need to be improved in the coming years.
      Local and regional research into morbidity and well-being is important for policy
      formulation. The situation of different categories of chronically sick needs to
      be investigated. Improved health in childhood and middle age will probably be
      followed by improved health in old age, and this may offset the burden on the
      health care system of the growing number of elderly.

PMID- 9529745
TI  - Preventable blindness in the east African elderly.
AB  - The epidemiology and delivery of eye care for East Africa are outlined. The
      common causes of blindness in the elderly (> 60 years old) are discussed
      individually. Cataract causes (50%), trachoma (16%) and glaucoma (12%) of
      blindness in the East Africa Region.

PMID- 9529744
TI  - Median age at menopause in a rural population of western Kenya.
AB  - This was a cross sectional descriptive study to discuss the median age of
      menopause in a rural area of Western Kenya. The broad objective of the study was
      to describe the demographic and biophysical characteristics of the study
      population and determine the age of menopause. A review of the current and
      medieval records shows average age of menopause has remained relatively constant
      at 50 years in contrast to the receeding age of menarche. A total of 1078 women
      aged between 40-60 years were interviewed. The majority (98.8%) were from one
      ethnic group, the Luhya. Of the 1078 women, 880 (81.4%) were married and 198
      (18.6%) were single. The average number of children per woman was 7.74. Most of
      the women (75.1%) had attained primary school education. Their husbands were
      unskilled workers in 30.1% of the cases. The mean weight and height of the women
      was 60.74 kg and 161.1 cm respectively. Using methods of probit analysis, the
      median and modal age of menopause was found to be 48.28 years in this group of
      western Kenya women. If generalised for the whole country, these results suggest
      that an average Kenyan woman lives for over ten years beyond menopause. It is
      recommended that more attention should be given to the special health problems of
      postmenopausal population.

PMID- 9529746
TI  - Effect of ageing on androgen levels in elderly males.
AB  - The past four decades have brought with it modern medical technology accompanied
      by better quality and longer life resulting in the increase in number of aged
      males in this locality. It has now been well established by various investigators
      that there is a statistically significant decline of the biologically available
      level of serum testosterone with ageing. This decline in androgen levels is more
      manifest in the free testosterone levels compared to the total serum testosterone
      levels which are routinely measured in the laboratory. Not withstanding this
      statistical decline the serum testosterone levels in the majority of aged men
      often fall within the normal range (300-1000 ng/dl) of eugonadal young males.
      This age related decline is usually associated with decline in sexual function in
      ageing men manifesting as erectile dysfunction. However, it has now been
      established beyond doubt that age itself rather than the androgen decline is the
      most influential variable of sexual activity in old men.

PMID- 9529747
TI  - African perceptions and myths about menopause.
AB  - Menopause for most African women marks the end of reproductive potential. For the
      grand multiparous women deprived of modern contraceptive technologies it is also
      a relief from pregnancies; but to the childless women it could be the beginning
      of a depression. Age per se is not as important a consideration as the events
      surrounding menopause. Cultural beliefs and practices vary with the different
      communities in Africa. It is important for health providers to identify such
      beliefs and practices if reproductive health problems that emerge in the
      climacteric have to be prevented and managed correctly.

PMID- 9529748
TI  - Cardiovascular disease in elderly in-patients at the Kenyatta National Hospital,
      Nairobi-Kenya.
AB  - A prospective study to determine the prevalence and profile of cardiovascular
      disease in elderly patients admitted into the medical wards, Kenyatta National
      Hospital, was carried out between July 1991 and January 1992. Two hundred and two
      patients over 60 years of age were admitted into the medical wards over this
      period. This formed seven per cent of the total medical admissions. Two of these
      refused to take part in the study. Of the 200 elderly patients evaluated for
      cardiovascular disease, 146 (73%) were between 60 and 75 years of age with only
      26 (13%) being over 85 years. Fifty seven per cent were males. Clinical evidence
      of cardiovascular disease was present in 79 (39.5%) of the patients evaluated.
      There was no sex difference in the prevalence of cardiovascular disease as judged
      from clinical evaluation (37.7% males versus 41.9% females, p > 0.05).
      Cardiovascular diseases in our medical in-patients at Kenyatta National Hospital
      are common and especially so with hypertension which plays an important role in
      the aetiology of congestive heart failure and cerebravascular accidents. Cardiac
      arrhythmias are also common though not necessarily symptomatic. Rheumatic heart
      disease and cardiomyopathies were uncommon in our study population. A community
      based survey is needed to determine the true prevalence of cardiovascular
      diseases in the elderly and their contribution to morbidity in this sector of the
      population.

PMID- 9529749
TI  - Anaesthesia in the elderly with special reference to management of orthopaedic
      patients.
AB  - Elderly patients are placing increased demands on the health care resources in
      Kenya. The population of old patients has increased and complex
      surgical/orthopaedic procedures are being done on old patients. Due to the normal
      physiological alterations that occur with age, as well as the effects of common
      chronic diseases, elderly patients are less resilient than younger patients and
      are at risk of developing a variety of intraoperative and postoperative
      complications peculiar to their age. If and when complications develop in the
      elderly patients they have no reserves to withstand them and recovery is
      prolonged. In this article we review the factors that affect the peri-anaesthetic
      patients with special reference to orthopaedic and trauma elderly patients and we
      highlight the factors that may modify the treatment and surgery in these
      patients. We also recommend modifications for developing countries to lessen the
      financial burden on health care units.

PMID- 9529750
TI  - Magnetic resonance imaging of the ageing brain.
AB  - Many changes occur in the brain with normal ageing. These have been extensively
      investigated by autopsy studies and more recently with high resolution MRI.
      Dementia is a major public health problem worldwide which affects the elderly
      population. Magnetic resonance imaging (MRI) is the imaging test of choice to
      identify underlying treatable causes of dementia, including normal pressure
      hydrocephalus, subdural haematoma and intracranial tumour. It is important to
      understand the normal changes which occur with ageing and these should not be
      interpreted as pathological lesions on MRI. Though there is considerable overlap
      between findings of normal and abnormal ageing brain, with a good clinical
      background, it is possible, in many cases, to suggest the diagnosis of
      Alzheimer's disease, multi-infarct dementia and various other pathological
      processes.

PMID- 9529751
TI  - Height and weight factors over the ages.
AB  - Finding a simple and easily reproducible formula for assessing fitness and growth
      for human body has been one constant search over the ages. It was the aim of this
      project to try and add to this search. Most formulae in this field have complex
      calculations. Most of them have been derived using single system measurements. To
      delineate our factor, multisystem measurements were used; metric and imperial.
      This yielded a factor for describing the relationship between weight and height
      over the ages. The height is in inches and weight in kilograms. This produced
      factors (D) and (G) which have childhood, adolescent, adult and old age values. A
      total of 368 black Kenyans were studied. The age range was 3-85 years.

PMID- 9529752
TI  - Screening and early detection for prostate cancer.
AB  - Prostate cancer is the most common malignancy in men. Mortality due to prostate
      cancer has continued to increase over the past five decades despite all the
      different options of treatment at the disposal of the urologist, such as,
      surgery, radiotherapy, chemotherapy and biotherapy. Presently, effective therapy
      for prostate cancer is only possible with early diagnosis of the disease still
      localised within the prostate. Recent studies have demonstrated that the present
      screening techniques including Digital Rectal Examination (DRE), Serum Prostate
      Specific Antigen (PSA) concentration, Transrectal Ultrasound (TRUS) and Random
      Ultrasonically guided multiple prostatic biopsies can detect some potentially
      curable asymptomatic localised cancers. The main goal of a cancer screening test
      is to help reduce mortality. To date, it has been established that screening
      increases early detection and survival but there is no evidence that screening
      reduces mortality. If in future early detection and intervention is proved to
      provide real benefit apart from the overdiagnosis of latent non aggressive
      tumours, then the mortality from prostate cancer could begin to decline in the
      next decade. However, if our current armamenteria of therapies continue to be
      ineffective in treating men with prostate cancer, the current emphasis on
      screening and early detection will decline.

PMID- 9529753
TI  - Apolipoprotein E polymorphism in elderly east Africans.
AB  - Current advances have shown the apolipoprotein E (APOE)-epsilon 4 allele to be
      highly associated with late-onset familial and sporadic Alzheimer's disease (AD)
      in Western populations. The association of APOE allele frequencies and dementia
      remain unknown in populations from developing countries. We recently initiated a
      project to examine APOE frequencies in non-demented and demented elderly East
      Africans. Blood DNA collected from two hospital-based populations showed that the
      APOE allele frequencies in a group of non-demented 67 Tanzanians over the age of
      65 years were found to be 14% for epsilon 2, 61% for epsilon 3 and 25% for
      epsilon 4. By comparison, the frequency of APOE-epsilon 4 in an age-matched
      demented group was also 25%. Assessment of APOE genotypes in the group of elderly
      Kenyan subjects from Nairobi also revealed high frequencies of the epsilon 4
      allele with no clear difference in frequency between demented and non-demented
      subjects. Our preliminary observations suggest that elderly East Africans with no
      apparent clinical AD possess relatively high APOE-epsilon 4 allele frequencies
      compared to normal ageing subjects from Western countries including African
      Americans. These results appear similar to those reported in a recent study in
      Nigerian Africans where a lack of correlation between APOE-epsilon 4 allele
      frequency and Alzheimer type of dementia was noted, and imply that APOE-epsilon 4
      allele may not necessarily be a risk factor in some populations of Africa.

PMID- 9529754
TI  - Ageing and cancer.
AB  - The process of carcinogenesis is complicated and in most cases requires several
      steps of cellular transformation resulting from various molecular signals brought
      about by interactions between carcinogens and the cellular genome. Cancers in
      which cellular transformation does not require numerous processes tend to occur
      in younger age groups while cancers of the advancing age tend to be those in
      which the process of cellular transformation occurs through complex molecular
      processes that require ample time for induction.

PMID- 9529755
TI  - Some claustral neurons projecting to various neocortical areas show morphological
      differences.
AB  - The morphology of claustral neurons projecting to the motor, somatosensory,
      auditory and visual cortical areas in the rat was analyzed by means of
      combination of axonal retrograde transport and morphometric analysis. Fluoro-Gold
      (FG) injections placed into various cortical fields resulted in labeling in the
      claustrum four neuronal types: pyramidal with thick main dendrite, oval with a
      few thin dendrites spreading out in various directions, fusiform possessing two
      main dendrites arising from opposite poles of the cell body and polygonal.
      Pyramidal neurons prevailed in populations of neurons projecting to the motor
      cortex of the contralateral hemisphere. Oval neurons outnumbered other types in
      populations projecting to the somatosensory, auditory and visual cortical fields.
      The number of fusiform and polygonal neurons did not exceed at 12.5% together in
      any populations. Neurons projecting to the contralateral hemisphere were the
      largest claustral neurons (mean cross-section are 167.19 +/- 2.9 micron 2)
      whereas neurons projecting to the motor cortex where the largest claustral
      neurons projecting ipsilaterally (141.89 +/- 2.22 micron 2). There was no
      significant difference between neurons projecting to the somatosensory (113.46 +/
      1.9 micron 2) cortex and to the visual (111.8 +/- 1.4 micron 2) cortex whereas
      neurons related to the auditory are (95.98 +/- 1.75 micron 2) were the smallest
      claustral neurons. These observations pointed out that the morphology of
      claustral neurons is closely related to a cortical area to which they send axons.

PMID- 9529756
TI  - Location and structure of the nuclei of epithalamus in hedgehog.
AB  - Studies were carried out on series of paraffin scraps stained by Nissl and Kluver
      Barrera methods. Habenular complex in hedgehog divides into nucleus habenularis
      medialis (hm) and lateralis (hl). These centers are located between anterior edge
      of commissura posterior and about 180 microns in front of posterior edge of
      corpus callosum. Length of hm is about 2.75 mm. The medial habenular nucleus is
      compact, well formed and outlined group of heavily stained mainly round cells. It
      has diveresely placed a drop-like shape, for long distance. On the dorsal side of
      hm there are a small more intensively stained neurons that vary from the
      remaining ones. The lateral habenular nucleus is shorter and less demarcated than
      hm. On the cross-sections, area of hlisat least twice larger than hm but its
      cells are very dispersed among strong myelinated fibers This nucleus most often
      has the shape of vertical or oblique band of neurons that generally are larger,
      paler stained and heteromorphic.

PMID- 9529757
TI  - Microscopic study of muscle spindles in recti muscles of human fetal eye.
AB  - Muscle spindles of recti muscles of the eyebulb appear in the 11th week of
      intrauterine life. At first, the spindle manifests the stage of myotube with 2-3
      intrafusal fibers and is surrounded by the monolayer of internal capsule. In the
      course of subsequent development, the number of intrafusal fibers increases.
      Internal capsule begins to demonstrate two layers (14th week) and, then, external
      capsule develops (17th week). In the 20th week, mature spindles have been
      observed with a multilayered external capsule.

PMID- 9529758
TI  - Number, length and localization of muscle spindles in recti muscles of the
      eyeball in human fetuses.
AB  - Studies were performed on recti muscles of the eyeball, isolated from human
      fetuses in 14th to 24th week of their development. Number of muscle spindles and
      their length increased with progressing age of the fetuses. Most numerous muscle
      spindles were present in the rectus inferior muscle. The spindles were spread
      along the entire length of the muscle. Somewhat more numerous spindles were
      present in the half of the muscle belly positioned from the side of original
      attachment (24th week). Spindles were localized in the peripheral part of the
      muscle.

PMID- 9529759
TI  - Variations in number and termination of the inferior thyroid veins in human
      fetuses.
AB  - In corrosion casts of the variations in termination of the inferior thyroid veins
      were investigated. The inferior thyroid veins drained into the left and right
      brachiocephalic veins to the superior vena cava and the internal jugular veins,
      and anastomosed with the thymic veins.

PMID- 9529760
TI  - Remarks on the arterial vascularization of double kidney.
AB  - In the material of 300 kidneys, collected from adult corpses of both sexes, the
      presence of double renal pelvis and duplicated ureter within the renal hilus was
      detected in 4 cases. In the investigated double kidneys the number of segmental
      arteries ranged from 4 to 6. In two out of the examined organs there were double
      posterior branches of the renal arteries and consequently, two posterior arterial
      segments. In two kidneys the segmental arteries crossed the urinary tract
      structures.

PMID- 9529761
TI  - Origin of the uterine artery in human fetuses.
AB  - Study was performed in 64 fetuses aged 9-40 weeks. In most of investigated
      fetuses (42 on the right side and 40 on the left side) the uterine artery arose
      separately from the internal iliac artery. It was also found that this artery
      originated as a common trunk with the pudendal, gluteal, middle rectal, and
      umbilical arteries.

PMID- 9529762
TI  - The official nomenclature of the articular facets for the rib on the thoracic
      vertebra: a case for revision.
AB  - In Nomina Anatomica 6th ed., the articular facets for the rib on the thoracic
      vertebra are called Fovea costalis superior, Fovea costalis inferior, and Fovea
      costalis processus transversi respectively. But, there is a little problem about
      the names of Fovea costalis superior and Fovea costalis inferior on the body of
      vertebra, because usually only one facet exists on each side of the body of 10th
      to 12th (or 9th to 12th) thoracic vertebra. This single facet on the body of
      vertebra should be called just Fovea costalis.

PMID- 9529763
TI  - Medical consultation for migraine: results from the American Migraine Study.
AB  - BACKGROUND: Migraine headaches are often disabling but usually responsive to
      treatment. Nonetheless, many people with migraine never consult a doctor for
      headaches. In a sample of the US population, we sought to determine the
      proportion of active migraineurs who ever consulted a doctor for headache and to
      identify the headache characteristics and sociodemographic factors associated
      with consulting. METHOD: A mailed questionnaire survey was sent to 15,000 US
      households, selected from a panel to be representative of the US population. Of
      20,468 eligible respondents ranging in age from 12 to 80 years, 2479 met a case
      definition for migraine. We mailed a second questionnaire to all migraineurs
      identified on the first survey and achieved a 69.4% response rate. The second
      survey assessed headache characteristics, patterns of medical care use,
      medication use, and method of payment for health care. RESULTS: Sixty-eight
      percent of female and 57% of male migraineurs reported having ever consulted a
      doctor for headache. Consultation was more likely with increasing age and in
      women who ever married. In females, several headache characteristics including
      pain intensity, number of migraine symptoms, attack duration, and disability were
      associated with consultation. Of those who never consult, 61% report severe or
      very severe pain and 67% report severe disability or the need for bed rest with
      their headaches. CONCLUSION: The results of this survey indicate that a
      significant proportion of migraine sufferers never consult doctors for their
      headaches. Given that a large proportion of persons who never consult report high
      levels of pain and disability, these data suggest that there are opportunities to
      appropriately increase health care utilization for migraine. Given that 40% of
      migraineurs who have ever consulted do not report a physician diagnosis of
      migraine, there is a need to improve headache diagnosis and/or doctor-patient
      communication about migraine.

PMID- 9529764
TI  - Headache and analgesic use in Sweden.
AB  - In this study, patterns of analgesic use among persons with headache in the
      general Swedish population were analyzed in association with health factors,
      health care utilization, sociodemographic factors, and life-style. Data from the
      Swedish Survey of Living Conditions for the 2-year period 1988 through 1989 were
      used. In this survey, a probability sample of the Swedish population aged 16
      years and older was interviewed. Persons with headache were identified by the
      question, "Have you (during the last 2 weeks) had recurrent headache or
      migraine?" Analgesic use was defined by the question, "Have you (during the last
      2 weeks) used prescription or nonprescription analgesics?" Persons who answered
      both these questions were included in the present study, yielding a study
      population of 11,975 persons. Sixteen percent of all women and 8.2 percent of all
      men reported headache. Seventy-four percent of all women with headache reported
      analgesic use as compared to 64% of all men with headache. Analgesic use
      increased with increasing age among women but not men. While few of the studied
      factors were associated with analgesic use among persons with headache, the
      associations found differed by gender. Poor social network and musculoskeletal
      pain were associated with analgesic use among men with headache; age, being
      underweight, and visits to a physiotherapist were associated with analgesic use
      among women with headache. Those studying medication use among persons with
      headache might consider including these factors in future studies to help better
      understand the mechanisms behind the decision to use or avoid analgesics.

PMID- 9529765
TI  - Acute treatment of periodic severe headache: comparison of three outpatient care
      facilities.
AB  - We compared treatment of patients with episodic, severe, migraine-vascular
      headaches in three outpatient settings associated with a major medical center:
      the Charlton Outpatient Therapy Center (COTC), a dedicated transfusion and
      injection facility which provides treatment based on physician orders written in
      advance of the patient's visit; a walk-in Urgent Care Center (UCC); and a
      traditional hospital emergency trauma unit (ETU). For a 7-month period in 1995,
      all patient visits for acute migraine headache to the COTC, UCC, and ETU were
      reviewed. Data collected included the treatment and charges. After the study
      period, a sample of patients was surveyed regarding their outcome and
      satisfaction with care at each of the three facilities. During the study period,
      15 patients visited the COTC 446 times for the treatment of acute migraine, 80
      patients visited the UCC 233 times, and 182 patients visited the ETU 238 times.
      The average charges per visit were $39.93 for the COTC, $57.28 for the UCC, and
      $317.71 for the ETU. Average time spent in order to obtain care was 35 minutes in
      the COTC, 62 minutes in the UCC, and 105 minutes in the ETU. Intramuscular
      meperidine with either promethazine or hydroxyzine was the most commonly
      administered treatment in all three settings. Patients treated in the COTC
      reported greater satisfaction than the patients seen in the UCC or ETU. A
      dedicated outpatient facility with extended hours of operation and the capability
      of treating acute headache patients with parenteral medications based on standing
      orders has provided a community of migraine sufferers with cost-effective care.

PMID- 9529766
TI  - Hyperbaric oxygen in the treatment of migraine with aura.
AB  - Cephalalgia is one of the most common medical complaints and the search continues
      for relief. Early treatments for migraine included inhalation of 100% oxygen. It
      has been theorized that the increased levels of oxygen in the blood act as an
      alpha-adrenergic agent to alleviate headache pain through vasoconstriction and
      local metabolic effects. The presence of muscle tenderness during some migraine
      headaches has also been established. The purpose of this study was to document
      relief of cephalalgia through use of a visual analog pain scale, algometry, and
      manual palpation. Female subjects with confirmed migraine were randomly assigned
      to begin with either the control (100% oxygen, no pressure) or hyperbaric
      treatment (100% oxygen, pressure). Manual palpation and algometry of 10 sites
      were done, bilaterally, by a trained specialist. Pain was evaluated with a visual
      analog scale. Resolution of tenderness and edema following both treatments was
      observable by manual palpation while algometry showed no differences between the
      two. Subjective pain was significantly decreased following hyperbaric oxygen
      treatment but not following the control treatment. Results suggest that
      hyperbaric oxygen treatment reduces migraine headache pain and that the patient's
      subjective assessment was the best indicator of relief.

PMID- 9529767
TI  - Stress, headache, and physiological disregulation: a time-series analysis of
      stress in the laboratory.
AB  - This study examined the stress-headache relationship from a disregulation
      framework by monitoring both physiological responses (e.g., pulse, blood volume,
      skin resistance, and EMG) and self-reported responses to a stressful event in
      tension and migraine headache sufferers, as well as in headache-free controls.
      Responses were analyzed via time-series analyses to determine whether self
      reports of stress were correlated with physiological measures of stress. It was
      hypothesized that tension and migraine headache sufferers would show fewer
      significant correlations than control participants between their self-reports of
      stress and physiological activity. Data analyses supported this hypothesis for
      tension headache sufferers, but generally not for migraine headache sufferers.
      The most compelling support for the hypothesis in tension headache sufferers came
      from the cross-correlations between self-reported stress and pulse rate.

PMID- 9529768
TI  - Chronic paroxysmal hemicrania and hemicrania continua. Parenteral indomethacin:
      the 'indotest'.
AB  - The interval between indomethacin administration and clinical response may be
      clinically relevant in the assessment of chronic paroxysmal hemicrania and
      hemicrania continua and other unilateral headache disorders with which they can
      be confounded. Eight patients with chronic paroxysmal hemicrania (6 women and 2
      men) and 12 patients with hemicrania continua (8 women and 4 men) were entered
      into the study. The patients were given 50 mg of indomethacin intramuscularly
      (i.m.) on day 1 and some of them 100 mg IM on day 2 in an open fashion. The usual
      attack pattern was reestablished prior to the second test. The mean interval
      between attacks before the two injections (51 +/- 18 minutes) in chronic
      paroxysmal hemicrania was significantly shorter than the mean after each of the
      two indomethacin injections (50 mg = 493 +/- 251 minutes; 100 mg = 668 +/- 211
      minutes; P < 0.001; Mann-Whitney test). In every patient, there was a clear
      refractory period after indomethacin. Since the first "expected" attack after
      indomethacin administration did not occur, it can, with reasonable certainty, be
      assumed that the protective phase was initiated already prior to the time of the
      next "anticipated" attack. The mean attack duration was 22 minutes (last three
      attacks prior to test). The mean interval between the onset of two consecutive
      pretest attacks was 73 minutes. Since the interval between attacks was rather
      stable, one is, therefore, probably allowed to assume that the absolute
      protective effect of indomethacin on average had begun somewhere between 22 (mean
      attack duration) and 73 minutes after indomethacin injection. Similarly, in
      hemicrania continua, the time between 50-mg indomethacin injection and complete
      pain relief was 73 +/- 66 minutes. The pain-free period after indomethacin
      injection was around 13 hours (i.e., 13 +/- 8 hours after 50 mg and 13 +/- 10
      hours after 100 mg). The use of a test dosage of 50 mg of indomethacin IM
      ('indotest') gives a clear-cut answer and may be a useful tool in the diagnostic
      arsenal in every unilateral headache for a proper clinical assessment. A
      diagnosis of chronic paroxysmal hemicrania or hemicrania continua is a serious
      matter because it may imply life-long treatment with a potentially noxious drug.
      It is, therefore, of the utmost importance that an 'indotest' is carried out in a
      standard fashion. In the future, the rules set forth in the present context
      should be followed, at least in scientific studies. Pain pressure thresholds at
      cranial and extracranial levels were not significantly modified after
      indomethacin injection in any of the headaches.

PMID- 9529770
TI  - Cluster headache associated with parainfluenza virus, preceded and succeeded by
      migraine.
AB  - A serologically proven case of parainfluenza viral infection was associated with
      the onset and disappearance of cluster headache. The patient had long-standing
      migraine that ceased during the cluster headache period and recurred when the
      latter stopped. Possibly, the virus was neurally transmitted to the trigeminal
      autonomic system, creating an inflammatory response that transiently precipitated
      cluster headache and obliterated migraine.

PMID- 9529769
TI  - Trigeminal neuralgic-type pain and vascular-type headache due to gustatory
      stimulus.
AB  - We present a case of facial pain associated with sweet stimulus. An immediate,
      electric-like, short, unilateral pain was evoked by strong sweet gustatory
      stimulation. This was followed 6 to 8 hours later by a bilateral severe headache
      associated with bilateral tearing, rhinorrhea, periorbital swelling, flushing,
      and photophobia that lasted up to 2 days. The immediate pain that was
      experimentally induced with 2.5 grams of sucrose placed on the tongue could be
      abolished with carbamazepine. However, carbamazepine did not prevent the headache
      complex that appeared 6 to 8 hours later. Conversely, a trial with indomethacin
      abolished the late-onset headache, but not the immediate neuralgic-type pain. The
      independent nature of these pains suggests different pathophysiological
      mechanisms which are discussed.

PMID- 9529771
TI  - The transient syndrome of headache with neurologic deficits and CSF
      lymphocytosis. Report of a case without severe headache.
AB  - It has been recently reported that the occurrence of severe headache associated
      with temporary neurologic deficits and CSF lymphocytic pleocytosis is highly
      suggestive of the so-called "transient syndrome of headache with neurologic
      deficits and CSF lymphocytosis." In particular, in almost all of the 40 patients
      reported in the literature to date, the head pain was severe and of a type not
      previously experienced by the patient. In the present case report, we describe a
      patient who fulfilled almost all the proposed diagnostic criteria, except for the
      lack of a severe headache. Probably, a severe headache is not a compulsory
      feature of this syndrome. Some patients have rather mild headache accompanying
      their episodes of neurologic symptoms, and some attacks occur without any
      accompanying headache. It is possible that in some cases the absence of a severe
      headache, and thus the lack of CSF analysis, lead to misdiagnosis. Therefore, the
      prevalence of this syndrome could be underestimated.

PMID- 9529772
TI  - Masturbatory-orgasmic extracephalic pain.
AB  - Two single men, one with compressive spondylitic cervical myelopathy and another
      with tethered cord and intraspinal lipoma, experienced severe paroxysmal ice pick
      like pains, solely referred to the neck in the first and to the groin and
      genitalia in the second, that were precipitated by masturbation and masturbatory
      orgasms. Continuous, but less intense, background pain was reported by both
      patients over the same anatomic areas. Neither had intracranial lesions,
      epilepsy, or suffered from migraine. Recently, extratrigeminal ice pick status
      was reported in this journal. These two unusual cases represent examples of
      extracephalic ice pick-like pain triggered by sexual activity, in the absence of
      orgasmic cephalgia.

PMID- 9529773
TI  - Orthostatic headache.

PMID- 9529774
TI  - Transmission of genetically diverse strains of HIV-1 in Pune, India.
AB  - Surveillance of the different HIV-1 subtypes has important implications for
      developing candidate vaccines and understanding the dynamics of HIV transmission
      in various populations. In this study, HIV-1 viral subtypes were determined for
      homologies in the V3-V5 region by heteroduplex mobility assay (HMA) in 46
      patients with sexually transmitted diseases (STD) in Pune, India. Proviral DNA
      from peripheral blood mononuclear cells (PBMCs) from 20 recent sero-coverters and
      26 HIV seropositive individuals were analyzed. Of the 46 samples analyzed, 44
      (96%) were HIV-1 subtype C and one each of subtypes A and B. Further analyses
      revealed that 29 (66%) of the C subtype samples had maximum homology to the C3
      Indian reference strain, while 15 (34%) were most homologous to the C2-Zambian
      strain. The C3 genotype prevailed in the majority (80%) of the seropositive
      individuals. Most of the C3 (Indian) strains were closely homologous to each
      other, while more nucleotide sequence divergence was seen in C2 samples. A higher
      quasispecies complexity was observed in the samples collected from seropositive
      individuals. These findings may have important implications for the design and
      testing of effective candidate HIV-1 vaccines for India.

PMID- 9529775
TI  - Putative chikungunya virus-specific receptor proteins on the midgut brush border
      membrane of Aedes aegypti mosquito.
AB  - Two proteins (putative receptors) of 60 and 38 kDa, for chikungunya (CHIK) virus
      were detected in the brush border membrane fraction (BBMF) of the normal
      population of Aedes aegypti mosquitoes. Mosquitoes were infected orally with CHIK
      virus and infectivity checked by testing the head squashes. BBMF was prepared
      from proved positive and negative mosquitoes. The receptor proteins were found to
      be present in both the proved genotypes. However, dot-b'ot assays showed that the
      CHIK virus binding activity of BBMF/mg protein was noticeably low in the proved
      negative mosquitoes as compared to the positives. BBMF from the larvae of the
      normal populations also showed the presence of the receptor proteins, binding to
      CHIK virus. Receptor proteins from larvae as well as the adults were found
      glycosylated. CHIK virus receptor proteins of 24, 45, 58, 60 and 62 kDa were also
      seen in the membrane fraction of the C6/36 cells.

PMID- 9529776
TI  - Raised IgM antibodies to parvovirus B19 in juvenile rheumatoid arthritis.
AB  - To delineate the role of human parvovirus B19 in the etiopathogenesis of juvenile
      rheumatoid arthritis (JRA), IgM and IgG antibodies specific for parvovirus B19
      surface protein antigen(s) were estimated in the sera using commercial ELISA
      kits. Sera of 69 JRA patients (median age 16 yr, male : female ratio 1.1:1)
      satisfying the criteria of American Rheumatism Association along with 26 sera of
      rheumatoid arthritis (RA) and 12 sera of healthy children as disease and normal
      controls respectively were screened. Of the 69 patients with JRA, 19 (27.5%), 35
      (50.7%) and 9 (13%) were positive for IgM, IgG and both IgG and IgM antibodies
      respectively. Of the 26 disease control sera, 11 (42.3%) were positive for IgG
      antibodies while none had elevated IgM antibodies. Among 12 healthy controls, 7
      (58.3%) were positive for IgG and 1 was positive for both IgG and IgM antibodies.
      Thus, a statistically significant proportion of children with JRA had evidence of
      parvovirus B19 infection.

PMID- 9529777
TI  - Histopathological evaluation of inflammatory & hereditary demyelinating
      polyneuropathies.
AB  - In view of therapeutic implications and problems in clinical diagnosis, this
      study sought to evaluate and identify histopathological features of acquired
      inflammatory demyelinating neuropathies and hereditary demyelinating
      neuropathies. Sural nerve biopsies from 41 patients of demyelinating
      neuropathies, diagnosed on the basis of accepted clinical criteria, were studied
      using routine histological staining and special stains for myelin and axons.
      Chronic inflammatory neuropathies differed from the acute ones in having more
      endoneurial connective tissue, less of subperineurial oedema and presence of
      axonal sprouting and occasional onion bulb formation. Acquired neuropathies
      differed from hereditary neuropathies in having a more localized involvement,
      endoneurial oedema and variable inflammatory cell infiltration, while in
      hereditary neuropathies Schwann cell proliferation was diffuse and relatively
      uniform. The frequency and degree of nerve thickening was more in hereditary
      neuropathy. Evidence of inflammation was not universal, both in the acute and the
      chronic inflammatory demyelinating neuropathies. Histopathological examination is
      essential as the clinical and electrophysiological features alone may not offer
      definitive diagnosis.

PMID- 9529778
TI  - Triplet repeat polymorphism & fragile X syndrome in the Indian context.
AB  - Mental retardation due to fragile X syndrome is one of the genetic disorders
      caused by triplet repeat expansion. CGG repeat involved in this disease is known
      to exhibit polymorphism even among normal individuals. Here we describe the
      development of suitable probes for detection of polymorphism in CGG repeat at
      FMR1 locus as well as the diagnosis of fragile X syndrome. Using these methods
      polymorphism at the FMR1 locus has been examined in 161 individuals. Ninety eight
      patients with unclassified mental retardation were examined, of whom 7 were found
      to have the expanded (CGG) allele at the FMR1 locus. The hybridization pattern
      for two patients has been presented as representative data.

PMID- 9529779
TI  - Validation of expedient methods for measuring body composition in Indian adults.
AB  - The body composition of 99 men and 89 women from south India was estimated using
      hydrodensitometry, bioelectrical impedance and skinfold thickness. Comparisons of
      the hydrodensitometry (reference method) and skinfold methods showed that there
      were no significant differences between the methods, for estimates of fat free
      mass (FFM) and per cent fat. The mean difference between the estimates FFM
      (bias), from skinfold measurement and hydrodensitometry was small for both groups
      (+0.16 +/- 1.09 kg in men and +0.67 +/- 0.9 kg in women). The same trend was
      observed in per cent fat estimates (-0.37 +/- 2.04 in men and -1.49 +/- 2.28 in
      women), showing that the skinfold method can be used as an accurate and expedient
      method to determine body composition. The bioelectrical impedance method obtained
      a significantly lower FFM and higher body fat than the reference
      (hydrodensitometry) method. This could have been due to the use of an
      inappropriate equation derived from Western population studies. Hence, a new
      predictive equation, for the measurement of FFM by the bioelectrical impedance
      method was derived for this population, using the variables of height2/impedance
      and FFM measured by underwater weighing. The new equation for the bioelectrical
      impedance method then gave values of body composition which compared well (0.26
      +/- 2.32 kg) in men and (0.36 +/- 2.49 kg) in women with the hydrodensitometry
      method.

PMID- 9529780
TI  - Fit of Ehrenberg's equation to height & weight of young healthy Indian males.
AB  - Height-weight relationship in young healthy Indian males (16-21 yr) has been
      established for different states of India as well as for the combined data of all
      the states. It was observed that these relationships have large deviations of the
      intercepts and slopes from the intercept (a = 0.4) and slope (b = 0.8) of the
      Ehrenberg's equation. The results of the present study show that Ehrenberg's
      equation may not be applicable for young healthy Indian males aged 16-21 yr.

PMID- 9529781
TI  - Selective predictive value of rapid automatized naming in poor readers.
AB  - This study considers the differential predictive value of rapid naming tests for
      various aspects of later reading, where the differential is between nondisabled
      and poor readers. Two large-N longitudinal samples of students who have been
      evaluated from third through eighth grades are studied: (a) a randomly accessed,
      normally distributed group including students with varying degrees of reading
      ability (N = 154), and (b) a group of poor readers whose single-word reading in
      third grade is at or below the population 10th percentile (N = 64). Outcomes in
      fifth and eighth grade were measured in both groups. Single-word reading in both
      grades was strongly predicted from third-grade rapid naming only within the poor
      readers, even when IQ, socioeconomic status, and third-grade single-word reading
      were statistically controlled. Although rapid naming had predictive value within
      the large, normally distributed group, its predictive power was entirely absent
      in the average-reading nondisabled students who were between the 10th and 90th
      percentiles (n = 122). The fact that rapid naming has predictive power only for
      poor readers but not for average readers is interpreted as suggesting that
      impaired readers are qualitatively different from the normal-reading population
      and are not simply the "tail" of a normal distribution of reading ability. It
      also seems that it is the automaticity of retrieval, not the knowledge of names
      itself (as in confrontational naming tasks), that gives the predictive power in
      rapid naming. These data are considered in light of the one- and two-factor
      theories of the underlying processes involved in reading disability or dyslexia.

PMID- 9529782
TI  - Very-low-birthweight infants at seven years: an assessment of the health and
      neurodevelopmental risk conveyed by chronic lung disease.
AB  - To determine whether history of chronic lung disease (CLD) in children born at
      very low birthweight (VLBW) confers additional risk for impaired health, growth,
      and neurodevelopment, 17 VLBW children born in 1984 who had CLD (requiring
      supplemental oxygen more than 30 days after birth) in infancy and 28 VLBW
      children who did not have CLD were assessed at age 7 years. Assessments included
      a medical history, standard physical and neurological examinations, pulmonary
      function tests, and tests of neuropsychological and psychoeducational
      functioning. Health status did not differ between the groups. In contrast,
      children with CLD did not perform as well in neuropsychological and
      psychoeducational assessments. Although CLD confers little added risk to health,
      it seems to add significantly to risks for poor school performance that are known
      to be associated with very low birthweight.

PMID- 9529783
TI  - The middle school experience: effects on the math and science achievement of
      adolescents with LD.
AB  - The present study examined the relation between middle school transitions and
      achievement gaps in math and science between adolescents with and without
      learning disabilities (LD). An abundance of research indicates that motivation
      and achievement decline during the early adolescent years, and that this decline
      is often attributable to the transition from elementary to middle grade schools
      during early adolescence. Using data from the National Education Longitudinal
      Study, it was found that, on average, there was a strong gap in achievement
      between the two groups of early adolescents. Hierarchical linear modeling was
      used to examine school effects on these achievement gaps. Results indicated that
      although there were achievement gaps in math and science between adolescents with
      LD and non-LD adolescents, this gap was greatly reduced for adolescents who did
      not make a school transition until at least the ninth grade. It is proposed that
      the policies and practices of typical middle-grade schools are particularly
      incompatible with the educational and psychological needs of young adolescents
      with LD.

PMID- 9529784
TI  - An evaluation of the dyslexia training program: a multisensory method for
      promoting reading in students with reading disabilities.
AB  - The development of reading and spelling skills in students with dyslexia, by
      definition, is delayed and often remains delayed despite years of instruction.
      Three qualities are thought to facilitate reading development in these children:
      the provision of a highly structured phonetic-instruction training program with
      heavy emphasis on the alphabetic system, drill and repetition to compensate for
      short-term verbal memory deficits, and multisensory methods to promote
      nonlanguage mental representations. The Dyslexia Training Program, a remedial
      reading program derived from Orton-Gillingham methods, embodies these qualities.
      Following their 2-year program, students displaying dyslexia demonstrated
      significantly higher reading recognition and comprehension compared with a
      control group. The two groups did not differ in spelling. In addition, the degree
      of improvement in reading demonstrated by students who received the Dyslexia
      Training Program by videotape and by those who received it live from instructors
      did not differ.

PMID- 9529785
TI  - Inclusion or pull-out: which do students prefer?
AB  - The purpose of this study was to better understand students' perceptions of and
      preferences for inclusion or pull-out service delivery models. Thirty-two
      students with and without learning disabilities who had participated in both
      models during the past 2 or 3 years were interviewed individually. Key questions
      assessed their perceptions of which model was most conducive to academic learning
      and which was most likely to yield social benefits, and the reasons for their
      beliefs. Results indicated that students' views varied. Overall, more children
      identified pull-out as the model of choice, but many children were confident that
      inclusion was meeting their academic and social needs. We interpret the results
      of this study as providing support for maintaining a continuum of service
      delivery options and for considering the placement of each child individually,
      based on his or her unique needs.

PMID- 9529786
TI  - Mediators of the risk for problem behavior in children with language learning
      disabilities.
AB  - A developmental-organizational perspective was employed to explore underlying
      risk for problem behavior in children with language learning disabilities. The
      independent and relative influences of social discourse and social skills on
      problem behavior were examined in 50 children with language learning disabilities
      (LLD) and 50 control children (children without LLD) aged 8 to 12 years.
      Hierarchical regression analyses revealed that when examined independently, both
      impaired social discourse skill and poor social skills accounted for the negative
      effect of LLD status on children's problem behavior. When social discourse and
      social skills were examined simultaneously in relation to problem behavior,
      social discourse no longer retained its predictive value. This result suggests
      that children's impaired social interactional functioning is central to the
      development of behavioral symptomatology. However, the importance of social
      discourse cannot be overlooked, given the significant correlation between social
      discourse and social skills ratings. Though these results are correlational in
      nature, it is argued that the impaired communicative competence of some children
      with LLD may contribute to poor social skills that ultimately manifest themselves
      as more clinical problem behaviors characterized by internalizing and
      externalizing symptomatology. Finally, differences were confirmed in social
      discourse performance, social skills, and problem behaviors between the children
      with LLD and the control group children. Findings emphasize the importance of the
      routine assessment and monitoring of broader social discourse skills, in addition
      to social competence, in children with LLD.

PMID- 9529787
TI  - Loneliness and coherence among preschool children with learning disabilities.
AB  - This study investigated loneliness and coherence among Israeli preschool children
      with learning disabilities, in an attempt to identify the sources of social
      deficits before academic failure was established. The sample consisted of 187
      preschool children divided into three groups: (a) 60 children at high risk for
      developing learning disabilities (LD) in six mainstreamed preschool settings (47
      boys and 13 girls), (b) 76 nonhandicapped peers from the same preschools (56 boys
      and 20 girls), and (c) 51 children (38 boys and 13 girls) at high risk for
      developing LD who were regular students at 17 preschools and received special
      help in the afternoons outside their educational settings, at a regional learning
      center for students with LD. The research instruments consisted of the Children's
      Sense of Coherence Scale, the Loneliness Scale, a peer nomination procedure, and
      teachers' ratings. Two-way MANOVAs demonstrated that the two groups of children
      (Groups [A] and [C]) with LD and with a high risk for developing learning
      disabilities experienced higher levels of loneliness and lower levels of
      coherence. A subgroup examination revealed that they were less accepted by
      nondisabled peers and had less reciprocal nominations. Furthermore, their
      teachers viewed them as showing more maladjustment.

PMID- 9529788
TI  - Special education in Russia: historical aspects.
AB  - Tracing the history of special education services in Russia from its beginnings
      in the early nineteenth century through the rapid expansion of both private and
      government-supported programs and institutions until the restrictive Soviet
      period provides both understanding and appreciation of current Russian special
      education services and institutions. Theoretical principles guiding special
      education formulated by L. Vygotsky, and sources outside the USSR, were
      officially suppressed, as were testing and statistical data on handicapped
      individuals. Official mandates to bring students with handicaps up to state
      approved standards resulted in the development of creative, effective approaches.
      The framework of special education changed little until the breakdown of the
      USSR. The new Russian Federation ratified UN resolutions protecting the rights of
      children. Categorical language is a recent development, and terms such as
      defective, retarded and pedologist are gradually being replaced. The final decade
      of this century is witnessing rapid change at the initiation of the Ministry of
      Education that is beginning to produce needed reform. One of the major
      initiatives is to provide LD specialists in all schools so that students will not
      need to be a great distance from home to receive needed services.

PMID- 9529790
TI  - Russian "defectology": anticipating Perestroika in the field.
AB  - Created as a part of the general Russian educational system, special education in
      Russia has mirrored all the good and bad qualities of that system. It was during
      the Soviet phase of its existence that Russian remedial education developed its
      specific and unique character, reflecting the structure and values of the global
      social environment. Despite the fact that Russian society realized the need to
      change its general educational system, remedial education remained untouched by
      reconstructive forces. This article discusses both the background and the current
      state of treatment of children with disabilities in Russia. The theoretical basis
      of the modern Russian approach to disability, the current needy population, and
      the existing system for referral and rehabilitation are described, and emerging
      trends and new perspectives on the Russian treatment of children with
      disabilities are presented.

PMID- 9529789
TI  - Special education in Russia: history, reality, and prospects.
AB  - Special education in Russia is undergoing major change. It is shifting from a
      system that was first established under the Soviet communist regime over 70 years
      ago to one that reflects a more humanistic view of children with disabilities. To
      describe special education in Russia, this article (a) explains the background
      information on the formation of a Russian-American partnership, (b) offers an
      historical perspective of special education in Russia, (c) reviews the current
      status of special education in Russia and in particular the Sverdlovsk Oblast,
      and (d) forecasts future directions of Russian special education. In considering
      new goals and future directions for special education in Russia, the authors
      suggest that the policies and legislation developed by the Provinces in Canada
      may offer a workable model for a Russian special education system.

PMID- 9529791
TI  - Interdisciplinary order for seclusion or restraint: a new tool to enhance
      compliance with Joint Commission Standards.

PMID- 9529792
TI  - Nursing and threats to patient and nurse safety and quality of patient care.
AB  - A major effect of today's emphasis on cost-cutting in health care has been
      reductions in the numbers and mix of registered nurses (RNs). RNs have increased
      concerns over patient and practitioner safety and patient care quality. The
      American Nurses Association (ANA) has a major, multi-phase project addressing
      these concerns, called Nursing's Safety and Quality Initiative. This initiative
      encompasses: nursing-sensitive quality indicators, educating staff nurses,
      researching the impact of skill mix on patient outcomes, political activities, a
      national database of nursing quality indicators, and liaisons and coalitions.
      These activities reflects ANA's commitment to patient and nurse safety and the
      quality of patient care.

PMID- 9529793
TI  - Multidimensional performance measurement.
AB  - Assessing performance in today's complex health care environment presents a
      challenge to the nursing profession. In order to effectively evaluate performance
      within this complex and evolving health care environment, evaluation from
      multiple sources is required. This article describes a multidimensional
      performance measurement model that has patient care delivery at the center. This
      model may be used to evaluate performance of an individual provider or of an
      entire health care system.

PMID- 9529794
TI  - Professional standards: linking care, competence, and quality.
AB  - Professional standards are key to the success of nurses as health care evolves,
      new roles are created, and new practice settings established. They are the
      infrastructure beneath the development of institutional standards of care,
      competency-based education programs, and quality assurance programs. Using them
      to link these key components provides for consistency across practice settings
      and among practicing nurses within integrated delivery systems. They also serve
      as the foundation for consensus building for partnerships and interdisciplinary
      initiatives.

PMID- 9529795
TI  - Credentialing and privileging nurse-midwives.
AB  - Nurse-midwives are one category of advanced practice nurse increasingly seeking
      hospital privileges to admit patients on their own recognizance. This article
      provides a framework for those health care institutions and insurers who are
      credentialing nurse-midwives. Nurse-midwifery educational preparation, licensure,
      scope of practice, relationships with collaborative physicians, and professional
      liability are discussed. Standards of the Joint Commission on Accreditation of
      Healthcare Organizations that pertain to credentialing and privileging
      nonphysician providers are reviewed. Various privileging routes are explored and
      directions recommended.

PMID- 9529796
TI  - Multidisciplinary credentialing and privileging: a unified approach.
AB  - A health care organization's thoughtful and rigorous credentialing and
      privileging process is not only required by state and federal regulations but is
      essential for building a quality professional staff. The addition of nonphysician
      providers has challenged organizations to articulate the appropriate
      credentialing process for these providers. Further, the credentialing process has
      been burdened by the redundancy created when providers require credentialing and
      privileging by multiple health care settings and managed care organizations. This
      paper describes a multidisciplinary credentialing and privileging system of the
      highest standard that minimizes effort and expense for both the provider and the
      organization.

PMID- 9529797
TI  - Meeting Joint Commission requirements for staff nurse competency.
AB  - Changes in the health care industry have created great challenges for leaders of
      acute care organizations. One of the greatest challenges is ensuring a competent
      nursing staff to care for patients within this changing environment. This article
      will describe how our organization uses Joint Commission standards to assess,
      maintain, and improve the competency of nursing staff.

PMID- 9529798
TI  - An interdisciplinary approach to process performance improvement.
AB  - Today quality care is not driven solely by the professional integrity of health
      care providers. Quality is demanded and defined by health care consumers. To
      survive within the competitive health care market, quality is a priority
      initiative for most health care organizations. The Joint Commission on
      Accreditation of Healthcare Organizations (Joint Commission) requires
      interdisciplinary performance improvement activities to ensure continuous quality
      improvement. Johns Hopkins Bayview Medical Center has a Quality Management
      Structure that ensures performance improvement initiatives are interdisciplinary
      and directed toward the organizational mission and vision. The Clinical Value
      Compass and FOCUS-PDCA provide clear direction for performance improvement
      initiatives and foster agreement on the clinical outcomes, functional needs,
      satisfaction, and cost.

PMID- 9529799
TI  - Hearing the voices of women in war through continuous quality improvement.
AB  - During the war in Bosnia-Herzegovina (BIH), the infrastructure of the health care
      system was destroyed and health officials, health care providers, and women
      experienced the war from their own perspectives. Using the principles of
      continuous quality improvement (CQI), these perspectives were honored and served
      as the basis for an international training program to hear the voices of women in
      war and the concerns of those who cared for them. With the results of a
      comprehensive national survey of all partners, the World Health Organization's
      European Regional Office held a five-day workshop that used CQI methods. The
      facilitators and 18 nurses, midwives, and physicians from six cantons developed
      interventions to address the women's needs, as detailed from the women's stories
      and from the professional perspectives of governmental authorities and health
      providers. The effort illustrates the ways in which the principles and tools of
      CQI can be used to capture the needs of the users of the services with those
      responsible for restructuring the health service and those with overall
      responsibility for the health of woman throughout the country.

PMID- 9529800
TI  - The quality evolution in managed care organizations: shifting the focus to
      community health.

PMID- 9529801
TI  - A survey of multicultural awareness among hospital and clinical staff.

PMID- 9529803
TI  - More to it than CPR.

PMID- 9529802
TI  - And then there were none.

PMID- 9529804
TI  - More on mandibular molars.

PMID- 9529805
TI  - Assessing the relationship between dental disease and coronary heart disease in
      elderly U.S. veterans.
AB  - Several recent studies have shown a link between dental disease and coronary
      heart disease. The authors studied 320 U.S. veterans in a convenience sample to
      assess the relationship between oral health and systemic diseases among older
      people. They present cross-sectional data confirming that a statistically
      significant association exists between a diagnosis of coronary heart disease and
      certain oral health parameters, such as the number of missing teeth, plaque
      benzoyl-DL-arginine-naphthylamide test scores, salivary levels of Streptococcus
      sanguis and complaints of xerostomia. The oral parameters in these subjects were
      independent of and more strongly associated with coronary heart disease than were
      recognized risk factors, such as serum cholesterol levels, body mass index,
      diabetes and smoking status. However, because of the convenience sample studied,
      these findings cannot be generalized to other populations.

PMID- 9529806
TI  - Relationship between tobacco use and self-reported oral hygiene habits.
AB  - A sample of 34,897 dental patients completed written surveys assessing their
      tobacco use, frequency of brushing and flossing and perception of oral health
      problems. Brushing two times per day was reported by 73.5 percent of the patients
      and flossing one time per day by 35.6 percent. Tobacco users brushed and,
      particularly, flossed much less frequently than did nonusers. Compliance with
      daily flossing regimens was particularly low among smokeless tobacco users.
      Tobacco users also reported more oral health problems.

PMID- 9529807
TI  - Bonded amalgam sealants: two-year clinical results.
AB  - The authors used bonded amalgams as pit and fissure sealants without mechanical
      preparation. They compared the two-year retention of the bonded amalgams with
      that of resin-based pit and fissure sealants. Clinical examinations at six
      months, one year and two years revealed no difference between the retention of
      the two sealants. This technique opens up the possibility of using bonded amalgam
      in pits and fissures surrounding very conservative preparations in a preventive
      amalgam restoration.

PMID- 9529808
TI  - Lupus erythematosus: considerations for dentistry.
AB  - Lupus erythematosus, or LE, is a connective tissue disease that affects a number
      of organ systems. Patients with this condition can experience several other
      serious conditions--bleeding, infection, endocarditis, adrenal insufficiency and
      mucocutaneous disease--that can affect the provision of dental care. The authors
      describe considerations for managing dental treatment of patients with LE.

PMID- 9529809
TI  - Knowledge and attitudes among California dental care providers regarding child
      abuse and neglect.
AB  - The authors surveyed California dentists about their knowledge, attitudes and
      practices regarding child abuse and neglect. Only 16 percent of the respondents
      claimed to have seen or suspected a case of child abuse or neglect during the
      preceding five years, and only 6 percent claimed to have reported such a case.
      The authors also found that the respondents had little knowledge of California
      law regarding the reporting of such cases and little information or training in
      diagnosing and reporting suspected child abuse and neglect.

PMID- 9529810
TI  - Caries risk assessment: relevance to the practitioner.
AB  - The dental literature is filled with recommendations for assessing the caries
      risk of patients. Some of these recommendations are based on sound research, some
      on clinical experience. This article attempts to explain the science of risk
      assessment.

PMID- 9529812
TI  - Distinguishing Mars from Venus: emergence of gender biology in health and
      disease.

PMID- 9529811
TI  - How the trend to elective dental procedures influences your practice.

PMID- 9529813
TI  - Defamation and the Internet.

PMID- 9529814
TI  - A 30-minute in-office indirect composite inlay technique.

PMID- 9529815
TI  - A technique to simplify radiograph duplication.

PMID- 9529816
TI  - Differences in net incomes of male and female owner general practitioners.
AB  - The authors analyzed the mean net income of a cohort of male and female dentists
      with similar demographics and practice characteristics. The authors found that
      the average net income of these male dentists is higher than it is for their
      female counterparts. This difference is statistically significant and monetarily
      tangible, amounting to an annual net income balance of about $26,000 (22 percent)
      in favor of male dentists. If such a difference in net income persists, it could
      affect the profession as well as the distribution of dental school enrollments.

PMID- 9529817
TI  - Help smokers quit.

PMID- 9529818
TI  - Mitral stenosis in pregnancy.

PMID- 9529819
TI  - Quantitative analysis of hemispatial neglect in the intracarotid sodium
      amobarbital (ISA) test.
AB  - There are dramatic changes in the electroencephalogram of the inactivated
      hemisphere in the intracarotid sodium amobarbital test. One of the more profound
      behavioral changes during this procedure is left hemispatial neglect accompanying
      right hemisphere inactivation. The present study was designed to ascertain
      whether there was a clear relationship between the degree of hemispheric
      inactivation (as measured by the electroencephalogram) and the degree of left
      hemispatial neglect during this procedure. Sixty-nine participants undergoing
      right hemisphere intracarotid sodium amobarbital testing were presented with a
      random letter cancellation test at various points during the procedure. Neglect
      was quantified as significant, moderate, minimal, or none, based on how many
      target letters the patients missed. The simultaneous electroencephalogram from
      each of these testing points was spectrally analyzed and topographic maps were
      generated. The degree of neglect was then compared with the comparable
      topographic map. It was found that as the amobarbital-induced right hemispheric
      dysfunction regressed, the degree of neglect lessened in a systematic fashion, as
      did the profound electroencephalographic changes induced by the drug. Thus, there
      is a clear relation between the degree of hemispheric inactivation induced by the
      amobarbital and the degree of left hemispatial neglect. This relationship held
      regardless of side of hemispheric language dominance or epileptic focus. These
      results replicate previous findings that right hemisphere inactivation during the
      intracarotid sodium amobarbital test results in left hemispatial neglect. They
      extend these findings by clearly showing that neglect changes in a quantitative
      fashion (rather than being an all-or-none phenomenon) and further, show that
      there is a clear relationship between the severity of neglect and the degree of
      hemispheric dysfunction.

PMID- 9529820
TI  - Structural MRI correlates of recognition memory in Alzheimer's disease.
AB  - Neuroimaging and lesion studies have demonstrated that hippocampal volume
      correlates with memory performance, but material-specific lateralization of this
      structure-function relationship has been inconsistent. This MRI study examined
      the relative contributions of left and right temporal lobe volumes to verbal and
      nonverbal recognition memory in a group of 20 Alzheimer's disease (AD) patients.
      There was a significant relationship between extent of right hippocampal and
      right temporal gray matter tissue volume deficit and performance on the face
      recognition subtest of the Warrington Recognition Memory Test. The face
      recognition test correlated with right hemisphere volume but not to left,
      indicating a material-specific relationship between brain structure and function
      in this patient group. Right temporal horn volume did not account for a
      significant proportion of variance in face recognition memory. Although word
      recognition was not significantly correlated with either left or right
      hippocampal volume in the total group, there was a strong correlation between
      left hippocampal volume and word recognition memory in the female AD patients.
      Thus, face recognition shows a material specific relationship with select
      lateralized hippocampal and temporal cortical volumes in AD patients, regardless
      of gender, whereas the verbal recognition-left-hippocampal volume relationship
      may be mediated by gender.

PMID- 9529821
TI  - Quantitative and qualitative differences in the verbal learning performance of
      elderly depressives and healthy controls.
AB  - We compared the verbal learning and memory performance of 57 inpatients with
      unipolar major depression and 30 nondepressed control participants using the
      California Verbal Learning Test. The effect of age within this elderly sample was
      also examined, controlling for sex, educational attainment, and estimated level
      of intelligence. Except for verbal retention, the depressive had deficits in most
      aspects of performance, including cued and uncued recall and delayed recognition
      memory. As well, there were interactions between depression effects and age
      effects on some measures such that depressives' performance declined more rapidly
      with age than did the performance of controls. The results are discussed in the
      context of recent contradictory reports about the integrity of learning and
      memory functions in late-life depression. We conclude that there is consistent
      evidence, from this and other studies, that elderly depressed inpatients have
      significant deficits in a range of explicit verbal learning functions.

PMID- 9529822
TI  - The effects of visual distraction following traumatic brain injury.
AB  - Clinical assessments of individuals with traumatic brain injury (TBI) typically
      report attentional difficulties, with distractibility prominent among these
      complaints. However, laboratory-based measures have often failed to find
      disproportionate distraction among patients with TBI, as compared to control
      participants. In this experiment, we tested 21 patients hospitalized for
      rehabilitation following recent TBI and 21 demographically comparable control
      subjects on a visual reaction time go-no-go task in which the target was preceded
      or followed by a brightly colored moving visual stimulus, appearing above the
      target location. Early distractors actually served as warning stimuli, improving
      accuracy and speed for both participant groups. Distractors occurring at or
      shortly after the time of target presentation had no significant impact on
      accuracy or response bias in either group, but did produce slowing of RT that was
      significantly greater for patients than for controls. The distractor that
      produced maximal slowing occurred 100 ms after the presentation of the target or
      foil. Repeated testing sessions led to reduction in the impact of the distractor
      and loss of the group difference in RT impact. The degree of RT slowing induced
      by distraction was modestly related to injury severity, as measured by the
      current score on the Disability Rating Scale, and the time until the patient
      first followed verbal commands. There was also a trend of greater RT slowing
      among individuals with focal orbitofrontal lesions, as assessed on neuroimaging
      studies. These results document a greater susceptibility to extraneous visual
      distraction among patients with TBI in comparison to controls. The fact that this
      difference appears only in the RT domain, and is greatest when the distractor
      follows the target, suggests that the primary impact of visual distractors is on
      response preparation and execution rather than target detection.

PMID- 9529823
TI  - Clustering and switching on verbal fluency tests in Alzheimer's and Parkinson's
      disease.
AB  - Two components of verbal fluency performance--clustering (i.e., generating words
      within subcategories) and switching (i.e., shifting between subcategories)--were
      examined in patients with dementia of the Alzheimer type (DAT), patients with
      dementia with Parkinson's disease (DPD), nondemented patients with Parkinson's
      disease (NPD), and demographically matched controls. The DAT and DPD groups were
      impaired in the number of words generated on both phonemic and semantic fluency.
      The DAT group produced smaller clusters on both tasks and switched less often on
      semantic fluency than controls. The DPD group switched less often on both tasks
      and produced smaller clusters on phonemic fluency than controls. The NPD group
      was not impaired on any fluency variable. Thus, the total number of words
      generated on phonemic and semantic fluency did not discriminate the dementia
      groups from their respective control groups, but measures of clustering and
      switching did. This differential pattern of performance provides evidence for the
      potential usefulness of measures of switching and clustering in the assessment of
      dementia.

PMID- 9529824
TI  - Visual selective attention after severe closed head injury.
AB  - This study investigated the nature of selective attention deficits after severe
      closed head injury (CHI). Twenty participants with severe CHI (greater than 1
      year postinjury) and 20 matched controls completed search and nonsearch visual
      selective attention tasks under conditions of low (Experiment 1) and high
      (Experiment 2) target-distractor similarity. In the search situations,
      participants searched visual displays that contained 1, 4, or 8 items for the
      targets. In the nonsearch situations, the location of the targets was visually
      cued with a peripheral arrow. The results revealed that in both the low and high
      target-distractor similarity search conditions. CHI participants required a
      longer time than controls to locate and identify the target. In contrast, in the
      nonsearch condition, CHI participants were able to successfully ignore irrelevant
      task information when target-distractor similarity was low. However, when target
      distractor similarity was high, CHI participants had more difficulty than
      controls ignoring the irrelevant information. These results suggest that, in
      comparison to controls, CHI participants may be at a disadvantage in selective
      attention situations when visual search is required and when the discriminability
      between targets and distractors is difficult.

PMID- 9529825
TI  - An examination of regional cerebral blood flow during object naming tasks.
AB  - The purpose of this study was to examine regional cerebral blood flow using
      positron emission tomography (PET) during the performance of tasks related to
      visual confrontation naming. Ten healthy, young participants were scanned twice
      in each of 5 conditions; blood flow was measured using standard PET [15O]-water
      technology. Two major findings have replicated previous studies. First, the
      naming of visually presented objects, whether covert or overt, requires a region
      of the left inferior cortex including the fusiform gyrus. Second, during overt
      naming, there is an increase in activity in the inferior or frontal cortex and
      insula as a consequence of generating speech code. These data are consistent with
      other studies demonstrating the importance of the inferior temporal regions for
      semantic processing, and the frontal cortex for word form generation.

PMID- 9529826
TI  - Neuropsychological performance in body dysmorphic disorder.
AB  - Fourteen patients with body dysmorphic disorder (BDD) were assessed with
      neuropsychological measures, including tests of executive, mnestic, and motor
      functions. Performance in these patients was compared to 10 patients with
      obsessive-compulsive disorder (OCD), 14 patients with schizophrenia, and 24
      normal controls. Findings indicated normal performance of the BDD group on
      measures of mnestic and motor function, but poor performance of this group on
      tests of executive function (p < .05). The overall performance of the BDD and OCD
      groups on the neuropsychological measures was similar, while the schizophrenic
      groups showed a wider spectrum of neuropsychological deficits to these groups.
      These findings are discussed in terms of current theories of executive functions
      and the possible relationship between BDD and OCD.

PMID- 9529827
TI  - Neurobehavioral functioning in asymptomatic HIV-1 infected women.
AB  - Numerous reports have assessed the neuropsychological functioning of medically
      asymptomatic HIV-1 infected men. However, to date there have been no published
      studies of the neuropsychological functioning of asymptomatic HIV-1 infected
      women, even though women represent the fastest-growing demographic group of HIV-1
      infected individuals. In this investigation, 31 women (17 asymptomatic HIV-1
      seropositive, 14 seronegative) were administered a battery of neurocognitive and
      neuropsychiatric instruments. Participants in both groups were matched for age,
      education, months since injection drug use, and substance use. Group comparisons
      revealed no significant differences in any of the neurocognitive or
      neuropsychiatric measures. The results of this preliminary study suggest that
      clinically significant differences in neurobehavioral function are unlikely in
      medically asymptomatic HIV-1 infected women compared to seronegative controls.
      However, additional studies are needed with larger sample sizes and with careful
      attention to possible confounding or masking variables.

PMID- 9529828
TI  - Acquired oral reading vocabulary following the onset of amnesia in childhood.
AB  - While the neuropsychological literature includes few cases of child-onset
      amnesia, 2 previous case studies suggest that these patients may be able to learn
      new information of a semantic or academic nature. The previous studies were, in
      large part, based on neuropsychological testing performed during adulthood and a
      retrospective review of academic achievement test scores during childhood. We
      present patient A.C., who acquired severe anterograde amnesia at age 10 years but
      demonstrated average levels of performance on tests of reading, spelling and
      arithmetic upon examination at age 19 years. Episodic and semantic memory test
      scores were severely impaired, but near normal performances were found on tests
      of implicit and procedural memory. In a prospective study, A.C. learned to read
      new irregular and pseudowords and retained this learning over a 1-month period,
      similar to the performance of age-matched controls. This demonstration of
      postmorbid, acquired oral reading vocabulary supports a previous conclusion that
      oral reading can progress in childhood following the onset of severe anterograde
      amnesia. The data also suggest that this new learning probably reflects
      nondeclarative memory processes rather than preservation of semantic memory, as
      was proposed in an earlier case study.

PMID- 9529829
TI  - Neuropsychological impairments following hantavirus pulmonary syndrome.
AB  - Recently an outbreak of acute respiratory infection associated with the
      hantavirus occurred in the southwestern United States. Hantavirus pulmonary
      syndrome (HPS) is a life threatening illness that carries with it a high
      mortality rate. Patients with HPS experience prolonged periods of hypoxemia
      requiring mechanical ventilation and treatment in intensive care units. We have
      recently seen 2 survivors of HPS. A neuropsychological test battery was
      administered immediately following their acute hospitalization and at 1 year
      postrecovery from HPS. Both patients exhibited cognitive impairments immediately
      following HPS as well as persistent cognitive impairments at 1 year. The
      cognitive impairments seen in these two HPS survivors are similar to those seen
      in other patients who have experienced brain anoxia, including memory
      impairments. It is also possible that hantavirus may directly cause brain injury
      with concomitant cognitive impairments. Additional research needs to be carried
      out in order to determine the extent and severity of the cognitive impairments in
      survivors of HPS.

PMID- 9529830
TI  - Kentucky's child restraint law has saved lives: a 20-year review of fatalities
      among children (aged 0-4) as motor vehicle occupants.

PMID- 9529831
TI  - Chronic cavitary pulmonary sporotrichosis: efficacy of oral itraconazole.
AB  - The small number of patients suffering from pulmonary involvement with Sporothrix
      schenckii has prevented prospective controlled studies that could determine the
      optimal therapy for this chronic infection. The clinician's ability to determine
      the best medical treatment for chronic cavitary pulmonary sporotrichosis is also
      tempered by the limited use of newer azole antifungal agents in this disorder as
      well as the relative lack of efficacy reported with older therapies. We present a
      50-year-old male with primary pulmonary sporotrichosis whose chronic cavitary
      disease responded to oral itraconazole.

PMID- 9529832
TI  - Financial planning considerations at retirement.
AB  - The process of retirement planning is a difficult one for a physician. The
      Planning process should address the areas of Investment Planning, Estate
      Planning, and Risk Management. This article examines each of these dimensions
      with special emphasis on Modern Portfolio Theory as the basis for investment
      planning.

PMID- 9529833
TI  - Telemedicine.

PMID- 9529834
TI  - Multiple intracranial aneurysms in Songklanagarind Hospital.
AB  - We retrospectively reviewed the 107 patients on whom direct surgery was performed
      for intracranial aneurysms between December 18, 1984 and July 25, 1996. The
      incidence of multiple intracranial aneurysms in our hospital is 6.5 per cent
      (7/107 cases). There were 16 aneurysms in 7 cases with multiple aneurysms. There
      were 2 and 5 patients with 3 and 2 aneurysms respectively. The most common site
      was at the junction of posterior communicating artery (PCoA) and internal carotid
      artery (ICA). The preoperative conditions of the patients were closely related to
      the operative results. We performed direct surgery on bilateral aneurysms by
      bifrontal approaches. There was no mortality.

PMID- 9529835
TI  - The further surgical experiences in intracranial meningiomas at Songklanagarind
      Hospital.
AB  - Meningioma is a common benign intracranial tumor documented in many reports. We
      retrospectively reviewed 81 patients with a total of 84 meningiomas. There were
      61 females and 20 males. Most patients were in the third to sixth decades of
      life. The most common presenting symptoms were headache and decreased visual
      acuity. Focal neurological deficits and signs of increased intracranial pressure
      were found in most patients. The three most common tumor locations were falx and
      parasagittal, sphenoid wing and convexity. Of the 84 meningiomas, 67 were
      completely resected and 17 were partially resected. Operative morbidities were
      accounted for by hemiparesis, cranial nerve palsy and infection. There was only
      one operative death in our series. 70 patients had normal and good results, 4
      patients had severe disabilities and results were unknown in 6 patients.
      Recurrences were detected in 8 patients and 5 patients underwent surgery again
      with good results in 4 patients. Recurrences occurred in 3 patients with total
      and 5 patients with subtotal resections. The most significant factor for
      recurrence was the extent of tumor resection.

PMID- 9529836
TI  - Clonidine for smoking cessation.
AB  - Clonidine was used to reduce withdrawal symptoms of nicotine and increase the
      success rate of smoking cessation in the smoking cessation clinic of Siriraj
      Hospital. One hundred and fourteen subjects enrolled in a double-blind,
      randomised, placebo-controlled trial. Subjects were divided as clonidine group (n
      = 58) with the mean age of 38 years and placebo group (n = 56) with the mean age
      of 33 years. Both groups received information about harmful effects of smoking as
      well as behavioral modification protocol. The dose of clonidine used in this
      study was 300 micrograms and the duration of the trial was 5 weeks. Both subject
      groups attended the clinic weekly and received identical counselling. Clonidine
      did not reduce withdrawal symptoms of nicotine when compared to the placebo and
      the success rate of smoking cessation at the end of the 5 weeks' period was
      identical between the two groups (clonidine 50%; placebo 48%, p > 0.05). No
      significant side effects of clonidine were found. There was no correlation
      between background educational level, income, amount of cigarettes smoked per day
      and the success rate in both groups. In conclusion, clonidine did not show any
      beneficial effect on smoking cessation.

PMID- 9529837
TI  - Similarity of bone mass measurement among hip, spines and distal forearm.
AB  - From January-December 1995, bone mineral density (BMD) of lumbar spine, hip and
      distal forearm were studied in 325 healthy women visiting the menopause clinic,
      Chulalongkorn Hospital. This retrospective analysis was conducted to assess the
      correlation of BMD among various measurement sites. Bone mass measurement at hip
      and spine were performed utilizing dual energy X-ray absorptiometer (DEXA),
      Hologic QDR 2000 and at distal forearm by single energy X-ray absorptiometer
      (SEXA), Hologic DTX 100. By canoconical correlation, the results revealed a
      significant correlation of BMD of distal and ultra-distal part of forearm with
      various sites of hip (r = 0.602, p < 0.001). There was also significant
      correlation of distal and ultra-distal part of forearm with various sites of
      spines (r = 0.619, p < 0.001). Though there is some heterogeneity of bone mass
      density among different measurement sites, practically with this fairly good
      level of correlation, bone mass measurement of distal forearm might be used to
      predict the BMD of hip and spine in Thai women. The accuracy of predicting the
      BMD of hip and spine by BMD of distal forearm in the mass screening programme in
      Thailand is now going on. The results will be followed.

PMID- 9529838
TI  - Radiofrequency catheter ablation for frequent premature ventricular contractions:
      a preliminary report of 15 cases.
AB  - Between February 1995 and March 1997, 15 patients, 13 women and 2 men, underwent
      radiofrequency catheter ablation (RFCA) for symptomatic frequent premature
      ventricular contractions (PVC's). The mean age was 43.3 +/- 11.9 years. Thirteen
      patients (86.7%) had right PVC's and the remainder had both right and left PVC's.
      RFCA were done under local anesthesia, using both earliest endocardial activation
      time and pace mapping in complement. The immediate success rate was 14/15 (93%)
      with only minor complications in 2 patients (13.3%). The fluoroscopic and
      procedure times were 40.6 +/- 24.0 and 170.7 +/- 81.2 minutes, respectively. From
      the Holter monitoring, total PVC count, per cent of PVC per total heart beat in
      24 hours and couplets count were significantly reduced, (more than 90%, p <
      0.05), by RFCA. Triplets and repetitive ventricular tachycardia were totally
      abolished. During the follow-up period of 10.1 +/- 7.5 months, 2 patients (14.3%)
      had recurrences of right PVC's within 2 weeks after ablation. Reablation was
      successfully done in both patients without recurrence, giving the final success
      rate of 93 per cent. In conclusion, RFCA could be safely performed with a high
      success rate in patients with symptomatic frequent PVC's. It can be considered an
      alternative treatment in patients resistant to medical therapy.

PMID- 9529839
TI  - Maternal and neonatal effects of single-dose epidural anesthesia with lidocaine
      and morphine for cesarean delivery.
AB  - Two per cent lidocaine (18-20 ml) with epinephrine 1:200,000 plus 4 mg of
      morphine was given as a single epidural injection over 3 minutes for elective
      cesarean section in 60 healthy mothers at term. It provided effective, safe and
      adequate analgesia in the postoperative period. There was no evidence of neonatal
      depression related to the epidural morphine as judged by Apgar scores at 1 and 5
      minutes and umbilical venous pH at birth. Maternal and umbilical venous levels of
      morphine were measured and found to be low at birth. However, this study was done
      only in healthy mothers not in labor and having a term fetus. We do not recommend
      using this technique in complicated obstetric patients.

PMID- 9529840
TI  - Lead exposure and accumulation in healthy Thais: assessed by lead levels, EDTA
      mobilization and heme synthesis-related parameters.
AB  - Lead is one of the pollutants which is of public concern. The magnitude of lead
      contamination in Thai people is of interest. The objective of this study was to
      evaluate the lead status in normal healthy volunteers. Normal volunteers were
      included. The blood for lead level, Zinc protoporphyrin (ZPP), delta
      aminolevulinic acid dehydratase (ALA-D) activity, and baseline urine for lead,
      delta-aminolevulinic acid (ALA) and coproporphyrinogen III (CP3) were collected.
      The EDTA mobilization test was done. 24 hour urine after administration of the
      drug was collected for lead analysis. Thirty volunteers were included in the
      study. All were men whose average age was 32.5 +/- 6.9 years. The mean lead level
      was 5.95 +/- 2.01 micrograms/dL and 5.83 +/- 2.32 micrograms/L in urine. The 24
      hour urine lead contents before and after EDTA administration were significantly
      different (11.11 +/- 6.72 and 16.05 +/- 9.51 micrograms respectively). Blood ALA
      D activity was 251.6 +/- 80.4 unit/ml of RBC. Urine ALA and CP3 were 0.56 +/- 1.2
      mg/L and 22.17 +/- 23.9 micrograms/L respectively. All were in the normal ranges.
      All parameters suggested that the healthy Thai volunteers had an acceptable
      magnitude of lead exposure and accumulation.

PMID- 9529841
TI  - Psychogenic vomiting 1976-1981, follow-up treatment results up to 1996.
AB  - During the period from 1976 to 1981, six children suffering from severe vomiting
      caused by psychological problems were admitted to Yuwaprasart Waithayopathum
      Hospital. These patients had been admitted to general hospitals from four to over
      ten times for the treatment of chronic recurrent vomiting, in each case the
      vomiting was very severe which caused dehydration. Three cases received surgical
      treatment, but abnormalities in the abdominal cavity were not seen in any of
      them. The treatment in Yuwaprasart Waithayopathum Hospital consisted of
      symptomatic treatment, medication, psychotherapy, behavior therapy, recreational
      therapy, occupational therapy, learning in special classes and family
      psychotherapy. Follow-up treatment results up to 1996 (20 years). The result
      revealed that five patients improved and were normal with subsequent
      discontinuation of all medication except one female patient who had moved with
      her family to another country.

PMID- 9529842
TI  - Anxiety and depression in teenage mothers: a comparative study.
AB  - A cross-sectional design study was done at a non-private ward at Rajvithi
      Hospital from June to August 1995 to determine the prevalence of anxiety and
      depressive state in Thai teenage mothers (< or = 18 years old) compared with
      adult control mothers (20-35 years old). We found that 15 per cent of teenage
      mothers and 12 per cent of adult control mothers had anxiety state. Twenty-three
      per cent of teenage mothers and 11.9 per cent of adult control mothers had
      depressive state. There was a significantly higher prevalence rate of depression
      in teenage mothers compared to adult control mothers.

PMID- 9529843
TI  - Knowledge, attitudes, and practices of senior high school students regarding
      human immunodeficiency virus infection.
AB  - A survey of knowledge, attitude and practice (KAP) regarding human
      immunodeficiency virus infection was performed on 899 students from 3 government
      administered high schools located in the Bangkok Metropolitan area. Initially,
      all students completed a written questionnaire (pre-test) regarding HIV/AIDS.
      Following this, they attended a slide lecture presentation given by a specialist
      physician. The same test questionnaire was then completed by the same students
      six weeks (post-test) later for comparison of their previous KAP. The subjects
      composed of male to female ratio equal to that of the median age 15-16 years old.
      Sixty-seven per cent of the subjects were living with their parents, 16.3 per
      cent with relatives and 15 per cent with friends. Ninety nine per cent of the
      subjects had received information on HIV/AIDS before enrollment to this study.
      The source of knowledge ranged from television (89.1%), teachers (81.6%),
      pamphlets (80.2%), newspapers (75%), radio (55%), health care workers (53.4%),
      friends (38.6%) and only 32.5 per cent from their parents. The subjects'
      knowledge about HIV/AIDS and risk factors in the post-test questionnaire was
      significantly increased (P < 0.001) from the pre-test status. However, their
      attitudes to an HIV infected person were not significantly changed in the post
      test questionnaire: only the "attending school" question showed significantly (P
      < 0.05) increased numbers of agreement. Similarly, the attitudes and practices to
      prevent HIV infection were not significantly (P > 0.05) different between pre
      test and post-test questionnaires. The result of this study is to recommend
      regular school-based programs of education to increase awareness of preventive
      strategies for HIV/AIDS and sexually transmitted diseases.

PMID- 9529844
TI  - Gentamicin pharmacokinetics in Thai neonates: recommendation for a dosing
      guideline.
AB  - A pharmacokinetic study of gentamicin was performed on 32 Thai neonates. After a
      single intravenous infusion of gentamicin at 2.5 mg/kg body weight, blood samples
      were collected at 0.5 and 12 hours. Serum gentamicin concentrations were
      determined with use of fluorescence polarizing immunoassay. None of the neonates
      with < 28 weeks post conceptional age (PCA), contrary to most of the more mature
      neonates, achieved the recommended therapeutic peak concentrations. The volume of
      distribution (Vd) and elimination half-life (T1/2) of gentamicin were found to
      reversely correlate with the PCA, with significantly larger Vd and longer T1/2
      values observed among the premature neonates. Our findings were similar the
      results previously reported in Caucasians, and thus strongly indicated the
      necessity of gentamicin dosage adjustment among Thai neonates according to their
      PCA. A gentamicin dosing guideline for Thai neonates has been proposed,
      nonetheless, with higher doses and longer dosing intervals recommended among
      premature neonates.

PMID- 9529846
TI  - Repair of nonunion lateral humeral condyle: a case report.
AB  - Epiphyseal injury of the lateral condyle of distal humerus is found commonly in
      children. Complications following such an injury can result in nonunion with late
      development of angular deformity and ulnar nerve neuritis. Nonunion at this area
      is extremely troublesome and difficult to treat. Controversy exists as whether
      late open reduction and fixation can restore the anatomy of the elbow joint and
      improve the function. We describe a technique of corrective osteotomy to correct
      the cubitus valgus deformity and repair the nonunion. The patient was treated
      successfully with 4 years follow-up.

PMID- 9529845
TI  - Methotrexate induced pericarditis and pericardial effusion in psoriatic patient.
AB  - We describe a 62-year-old woman with Psoriasis who presented as Methotrexate
      induced pericarditis and pericardial effusion. Aspiration of the pericardium was
      required and the patient made a satisfactory recovery. At six-months follow-up,
      she remained well, psoriasis plaques was controlled by topical crude coal tar and
      topical corticosteroid. These complications are extremely rare, but have been
      described as isolated phenomena associated with methotrexate therapy.

PMID- 9529847
TI  - Chlamydia pneumoniae: can it cause atherosclerosis?

PMID- 9529848
TI  - Sero-diagnosis of human brucellosis among TB suspected patients.
AB  - In order to verify the frequency of human brucellosis among a TB suspected
      population, a study was conducted on the basis of sero-diagnosis of a total of
      229 blood samples from TB suspected patients. Serological tests carried out were
      slide and semi-quantitative agglutination tests. Of the tested samples, 44
      (19.21%) were SAT positive and of these, 28 (12.23%) were positive for the
      semiquantitative agglutination test. Twelve (42.86%) had a brucella titer of
      1:80; 14 (50%) had a brucella titer of 1:160 and 2 (7.14%) had a titer of 1:320.
      The majority of patients positive for brucellosis, exhibiting sero-agglutination
      titers ranging between 1:40 and 1:320, were of rural background. However, 35.72%
      persons positive for brucella antibody with titer of 1:160 were from urban
      localities. Fever (84.48%), headache/dizziness (71.43%) and weakness/fatigue
      (46.43%) were the most common presenting symptoms among the brucellosis positive
      patients. The frequency of brucellosis among these TB suspected patients was
      found to be higher in women (73.91%), as compared to men (52.38%).

PMID- 9529849
TI  - Leishmanicidal activity of Nystatin (mycostatin): a potent polyene compound.
AB  - The susceptibility of promastigote of Leishmania major to Nystatin in vitro was
      examined. L. major (MHOM/PK/88/DESTO) promastigote were cultured in medium 199
      supplemented with 10% heat inactivated foetal bovine serum and 2% urine. The
      growth of the promastigote was monitored in the absence and presence of the
      experimental compound (Nystatin) for upto 5 days post-inoculation. The EC50 value
      (the concentration of drug necessary to inhibit the growth rate of cells to 50%
      of the control value) obtained for Nystatin against the promastigote of L. major
      was less than 9.76 iu ml. Certain polyene compounds like Amphotericin-B and
      Nystatin (mycostatin) are familiar for their fungicidal activity. Amphotericin-B
      is used since long as antileishmanial drug as well. Results obtained suggest that
      Nystatin has a very good anti leishmanial activity in vitro. The mode of action
      proposed for this drug is same as for Amphotericin-B as both of these polyene
      compounds interact with the various sterols present on the surface of the
      parasite, thus unusual gaps and pores are formed on the surface that results in
      the leakage of the ions. This leakage finally leads to the destruction of the
      parasite.

PMID- 9529850
TI  - Influence of anterior colporrhaphy with colpoperineoplasty operations for stress
      incontinence and/or genital descent on sexual life.
AB  - The effect of anterior colporrhaphy and colpoperineoplasty operation for stress
      incontinence and/or genital descent on sexual life was studied in 44 women. All
      sexually active cases prior to the operation for stress incontinence and/or
      genital descent were evaluated by interview and gynaecological examination
      immediately before and six months after the operation. Prior to the operation, 30
      out of 44 patients (68.2%), found their sexual life unsatisfactory because of
      various reasons like urinary incontinence, genital descent, vaginal relaxation
      and urinary incontinence during intercourse. Postoperatively, 20 (66%) of these
      30 patients improved, 4 (14%) showed no change and 6 (20%) deteriorated. Twelve
      of 14 (86%) patients who found their sexual life satisfactory before the
      operation described no change and 2 (14%) experienced deterioration
      postoperatively. Overall, 8 patients described deterioration postoperatively and
      all complained of dyspareunia. Colpoperineoplasty in combination with anterior
      colporrhaphy might cause dyspareunia in some patients. Colpoperineoplasty may
      increase the disturbances due to the atrophic changes related to menopause and
      should therefore be done selectively.

PMID- 9529851
TI  - Justification of caesarean section for fetal distress.
AB  - A study was done from May 1995 to February 1996 to evaluate the justification of
      caesareans for fetal distress by examining the circumstances leading to operative
      delivery for compromised fetus. Of the 1096 caesareans, 179 (16.33%) were for
      fetal distress. One hundred and seven (59.78%) were nulliparas and 127 (71%) came
      with the clinical features of fetal hypoxia. In 142 (79%) parturients at the time
      of c-section, cervical dilatation varied from 0-3 cm and in 144 (80%) the
      presenting part remained unengaged. The method most commonly employed to diagnose
      fetal distress was the external cardiotocography, used in 141 (79%) patients
      either alone or in combination with other options. Predictivity value of the
      parameters used to identify the fetuses at jeopardy was found to be more
      sensitive when used in combination. Neonatal outcome related poorly with the
      preoperative diagnosis if only one parameter was used. Poorest neonatal outcome
      was observed in the presence of thick particulate meconium. Great care should be
      exercised by the obstetricians while making a decision for caesarean for fetal
      distress so as to avoid unnecessary procedures and neonatal complications.

PMID- 9529852
TI  - Lipids in biliary lithogenesis.
AB  - Serum and biliary lipoproteins, total cholesterol (Tc) and triglycerides (TG)
      were measured in patients with gallstones and in those without gallstones. Serum
      and biliary LDLc, TG and Tc were significantly higher (P < 0.001) in cases having
      gall stones than those without stones while HDLc were low (P < 0.001) in those
      with stones. No difference was found in very low density lipoproteins (VLDLc) in
      the two groups. Present data showed that there is a statistically significant
      correlation of serum and biliary lipoproteins specifically LDLc and HDLc (r =
      +.67 and r = +.56). This report shows that serum HDLc (67.42%) and LDLc (70.28%)
      play a more critical role in comparison to total cholesterol (59.43%) and
      triglyceride (57.15%) levels in the formation of gallstone.

PMID- 9529853
TI  - The use of fine needle aspiration biopsy in the management of thyroid disease.
AB  - Fine needle aspiration biopsy is now a first line investigation in thyroid
      disease. The purpose of this study was to evaluate the results of this technique
      in comparison with routine histopathology. A total of 593 aspirations over a four
      year period were included. There were 390 (65.7%) solitary nodules, 124 (20.9%)
      multinodular goiters, 66 (11.1%) diffuse goitres and 13 (2.2%) recurrent post
      thyroidectomy nodules. Radioisotope scanning in 386 cases showed 325 (84.2%) cold
      nodules, 54 (14.0%) warm nodules and 7 (1.8%) hot nodules. There were 458 (77.2%)
      colloid goitres and cysts, 14 cases of thyroiditis (2.2%) and 30 malignancies
      diagnosed on fine needle aspiration biopsy. In 19 cases (3.2%) a diagnosis of
      follicular neoplasm and in 29 cases (4.9%) a diagnosis of suspicious aspirate was
      made. Histological results were available in 176 cases. In 108 cases findings of
      histology and FNAB were compared with radioisotope scanning. A sensitivity of
      92.8% and 42.8%, a specificity of 90.1% and 98.7% and accuracy index of 90.3% and
      94.3% was found, when considering suspicious cases alternatively as positives and
      negatives. Surgery was recommended in all suspicious cases to prevent reduction
      in sensitivity of the technique. Fine needle aspiration biopsy was found to be a
      highly effective procedure which can obviate a lot of unnecessary surgery in
      thyroid lesions.

PMID- 9529854
TI  - Mucinous cystadenoma of the urinary bladder.

PMID- 9529855
TI  - Renal tubular acidosis with muscle paralysis.

PMID- 9529856
TI  - Stevens-Johnson syndrome following measles vaccination.

PMID- 9529857
TI  - Radix auricularia coreana: natural snail host of Clinostomum complanatum in
      Korea.
AB  - An epidemiological survey was carried out to determine the first intermediate
      host of Clinostomum complanatum among freshwater snails in Korea. Two species of
      snails belonging to the family Lymnaeidae were collected in Kaum-ji (pond),
      Uisong-gun, Kyongsangbuk-do. Twelve (0.9%) out of 1,273 Radix auricularia coreana
      examined were found to liberate cercariae of C. complanatum, which were
      identified by morphological characteristics and experimental infections in
      freshwater fish. Pseudorasbora parva. The cercariae were brevifurcate and
      clinostomatoid. They had a transparent dorsal fin, a well developed penetrating
      organ and a pair of eye spots. The body measured 119-147 x 33-36 microns, tail
      stem, 275-370 x 19-26 microns, and furcae, 72-104 microns. Rediae were
      demonstrated in the infected snail after crushing. Redia, 527-1,630 microns long
      and 121-368 microns wide, contained 10-45 germ balls and cercariae in various
      developmental stages. The metacercariae recovered from fish experimentally
      infected with C. complanatum cercariae were morphologically identical to those
      from naturally infected fish.

PMID- 9529858
TI  - Ultrastructural changes of Acanthamoeba cyst of clinical isolates after treatment
      with minimal cysticidal concentration of polyhexamethylene biguanide.
AB  - In order to understand the action mechanism of polyhexamethylene biguanide (PHMB)
      to the cyst of Acanthamoeba on the morphological basis, the cysts of four corneal
      isolates of Acanthamoeba were treated with minimal cysticidal concentration (MCC)
      of PHMB and their ultrastructural changes were examined by transmission electron
      microscopy. The most striking change of cysts treated with PHMB compared with
      normal cysts was the shrinkage of intracystic amoebae, which resulted in the
      separation of the plasma membrane of intracystic amoeba from endocystic wall.
      Subplasmalemmal lipid droplets became irregularly shaped. In severely damaged
      cysts, cytoplasm was aggregated and organelles were severely deformed.
      Cytoplasmic materials were leaked out through the damaged plasma membrane. Most
      cysts showed aggregation of nuclear chromatin material. Number of mitochondrial
      cristae was also reduced. Ecto- and endo-cystic walls were relatively well
      tolerated. Findings in the present study revealed that PHMB affected mainly on
      plasma membrane, but lesser on organellar membrane of intracystic amoeba. It
      seemed likely that PHMB might kill cystic forms of Acanthamoeba by similar
      mechanism in which this environmental biocide can damage the cell wall of
      Escherichia coli by binding with acidic phospholipids.

PMID- 9529859
TI  - Development of an in vitro culture method for harvesting the free-living
      infective larvae of Strongyloides venezuelensis.
AB  - An in vitro culture technique was established for harvesting Strongyloides
      venezuelensis free-living infective larvae using a nutrient broth medium as a
      substitute for rat-feces in polyvinyl culture bags (10 x 12 cm). The egg hatch
      rate (Y) in sterile saline at different incubation temperatures (X) was expressed
      as the quadratic function, Y = -0.192X2 + 8.673X - 19.550 (r = 0.901). The
      highest (100%) egghatch rate was observed at 25 degrees C. A significant
      difference (p < 0.05) in development rate (Y) of free-living infective larvae was
      observed between different concentrations of nutrient broth (X) which was highest
      (20.6%) in 0.12% nutrient broth concentrations, incubated at 20 degrees C for 5
      days [Y = -864.032X2 + 245.995X - 0.560 (r = 0.875)]. Yields (Y) of infective
      larvae were observed relatively high when the culture medium was incubated at
      higher temperatures (X) which peaked at 25 degrees C (20.0%) than at lower
      temperatures, 15 degrees C (10.9%) and 20 degrees C (18.1%) [Y = -0.189X2 +
      8.387X - 72.795 (r = 0.981)]. The period (Y) required for the development of
      infective larvae decreased with higher incubation temperatures (X) [Y = 0.035X2 -
      2.025X + 32.375 (r = 0.995)]. The highest yield (19.2%) of infective larvae was
      obtained from culture bag inoculated with 15,000 eggs than with below and over
      15,000 eggs in 0.12% nutrient broth and incubated at 25 degrees C for 4 days. The
      newly adapted culture method (from egg to third-stage larva) may be useful as a
      bio-bar/bioassay system for screening new chemical products, anthelmintics and
      pesticides, as well as for parasito-immunological studies with Strongyloides
      species.

PMID- 9529860
TI  - [Comparison of virulence by Acanthamoeba strains in a murine model of acquired
      immunodeficiency syndrome].
AB  - The pathogenic potential of Acanthamoeba strains was evaluated by experimental
      infection of murine AIDS (MAIDS) model. C57BL/6 mice were induced to
      immunocompromized state by intraperitoneal injection of LP-BM5 MuLV and revealed
      the typical splenomegaly and lymphatic enlargement of axillar and inguinal
      regions on necropsy 4 weeks after viral infection. Although there was no
      significant difference in the mortality rate of MAIDS mouse according to the
      culture temperature, it was very different in the mortality rate from strain to
      strain of Acanthamoeba. A. healyi OC-3A strain isolated from the brain of a GAE
      patient showed the highest mortality rate and A. culbertsoni A-1 strain from
      tissue culture was the second. KA/S3 and KA/S2 strains isolated from soil
      revealed very low virulence. The mice infected by intranasal inoculation of
      Acanthamoeba showed relatively chronic course than intravenous inoculation. The
      gross findings of lungs and brains from infected mice were variable among mice.
      On the microscopic observations, the lungs showed much more severe inflammation
      and necrosis than the brains microscopically. This MAIDS model would be useful to
      study the opportunistic protozoan infections of AIDS patients. In the light of
      these results, the pathogenic potential and the virulence of Acanthamoeba may be
      determined genetically.

PMID- 9529861
TI  - Effect of Cryptosporidium baileyi infection on antibody response to sRBC in
      chickens.
AB  - Hemagglutinin (HA) titers to sRBC were chronologically observed in chickens
      orally inoculated at 2 days of age with 5 x 10(5) oocysts of Cryptosporidium
      baileyi. All the infected chickens exhibited negligible HA titers by 44 days
      postinoculation (PI). The titers were elevated as time progressed, and peaked on
      day 52 PI, declined gradually thereafter, and eventually reached to normal titers
      on day 92 PI. On the contrary, the titers in uninfected chickens were higher in
      comparison with infected chickens during the experiment. Chickens infected with
      the protozoa showed normal oocyst shedding profiles during this period. These
      data suggest that C. baileyi infection suppress development of humoral immunity
      to sRBC in chickens. It is possible that impairment of the bursa of Fabricius by
      cryptosporidiosis rendered chickens vulnerable to other pathogens.

PMID- 9529862
TI  - A Clonorchis sinensis-specific antigen that detects active human clonorchiasis.
AB  - A Clonorchis sinensis-specific antigen in excretory-secretory product of C.
      sinensis (CsE) was assessed in human clonorchiasis by immunoblot. Thirty and 7
      kDa antigens of CsE2, one of four different batches of CsEs reacted strongly with
      infection sera from clonorchiasis patients; however, the antigens reacted weakly
      with 6-month post-treatment sera from praziquantel-cured cases, but were still
      highly detected by the sera from praziquantel-failed patients, indicating that
      the 30 and 7 kDa antigens can detect antibodies during an active infection. The
      30 kDa antigen showed some cross reactions with sera from patients with
      Paragonimus westermani and Metagonimus yokogawai, while the 7 kDa antigen did
      not, suggesting that the 7 kDa antigen has high specificity. The 30 kDa antigen
      reacted with some past clonorchiasis sera, whereas the 7 kDa antigen did not,
      supporting that antibodies to the 7 kDa antigen are not present in sera from past
      clonorchiasis patients. In an endemic area, 92% (23/25) of active clonorchiasis
      patients and 91% (10/11) of mixed infection patients with C. sinensis and M.
      yokogawai had IgG antibodies to the 7 kDa antigen, while 40% (6/15) of past
      clonorchiasis individuals and 43% (3/7) of metagonimiasis patients cross-reacted
      to the antigen. These data suggest that the 7 kDa antigen in an excretory
      secretory antigen may serve as a marker of an active clonorchiasis with reliable
      specificities in past clonorchiasis, paragonimiasis and metagonimiasis.

PMID- 9529863
TI  - Identical small subunit ribosomal RNA gene nucleotide sequence of bovine
      Theileria isolates (Korea and Japan) and Theileria buffeli (Marula, Kenya).
AB  - Small subunit ribosomal RNA (SSU rRNA) gene nucleotide sequences of bovine
      Theileria isolates from Korea (KLS and KCB) and Japan (JHS) were determined. The
      genes from each isolate were amplified by the polymerase chain reaction and the
      approximately 1.8 kb product cloned and sequenced by a modified dideoxynucleotide
      method. Overlapping gene segments produced with a series of primers were
      sequenced, resulting in a complete DNA sequence for both forward and reverse
      strands of the SSU rRNA genes of each isolate. SSU rRNA gene sequences (termed
      Type A) were identical among the bovine Theileria isolates from Korea and the
      isolate from Japan. A GenBank data library homology search showed the sequence to
      be the same as that listed as Theileria buffeli isolated from cattle in Marula,
      Kenya.

PMID- 9529864
TI  - A small-scale survey of intestinal helminthic infections among the residents near
      Pakse, Laos.
AB  - A small-scale epidemiological survey was undertaken on the residents along the
      Mekong River near Pakse, Laos, to know the status of helminthic infections. A
      total of 137 fecal samples were collected from the staffs of the provincial
      government, their family, and primary schoolchildren in Pakse City, Champassak
      Province, and examined by Kato-Katz smear technique. The overall helminth
      positive rate was 75.9%, and the helminths detected were Opisthorchis viverrini
      (43.8%). Ascaris lumbricoides (26.3%), Trichuris trichiura (19.0%), hookworms
      (19.0%), Strongyloides stercoralis (2.2%), Taenia sp. (0.7%), and Schistosoma
      mekongi (1.5%). To obtain the adult worm of the liver fluke, three infected
      persons were treated with praziquantel and purged with magnesium sulfate. Five,
      10, and 395 adult flukes, respectively, were collected from their diarrheic
      stools, all of which were morphologically identified as O. viverrini. The results
      represent that the liver fluke and soil-transmitted helminths are highly
      prevalent, and the life cycle of S. mekongi is likely to be maintained in this
      area.

PMID- 9529865
TI  - A human case of tick bite by Ixodes nipponensis.
AB  - A human case of the tick bite on the back of 36-year-old man was found in
      September 1995. On admission he complained of itching sensation and pain at the
      site. The removed tick was identified morphologically as Ixodes nipponensis.

PMID- 9529866
TI  - A human case of tick bite by Ixodes persulcatus.
AB  - The first case of tick bite by Ixodes persulcatus in Korea is reported. The tick
      was found on the skin of right lower axilla region of a 60-year-old woman.

PMID- 9529867
TI  - Controversy--it's a good thing.

PMID- 9529868
TI  - Unlicensed assistive personnel: getting it right from the beginning.

PMID- 9529869
TI  - Maternal concerns about parenting prematurely born children.

PMID- 9529871
TI  - Should cameras be allowed in the delivery room?

PMID- 9529870
TI  - Sedating and monitoring pediatric patients. Defining the nurse's responsibilities
      from preparation through recovery.
AB  - Nurses play a vital role in ensuring the safety of children who receive sedative
      medications for diagnostic and therapeutic procedures. Established guidelines for
      providing care for this special population can be helpful in understanding how to
      fulfill this role. Nursing involvement in all phases of the sedation process not
      only promotes patient safety, but increases patient and family satisfaction.

PMID- 9529872
TI  - Congenital hypotonia is not benign. Early recognition and intervention is the key
      to recovery.

PMID- 9529873
TI  - Risk and resilience: building protective factors. An intervention for preventing
      substance abuse and sexual risk-taking and for promoting strength and protection
      among young, low-income Hispanic women.

PMID- 9529874
TI  - The significance of power in research design (Part I).

PMID- 9529875
TI  - Expanded health care coverage for needy children.

PMID- 9529876
TI  - Confronting the myths.

PMID- 9529877
TI  - Acknowledgment of infant loss.

PMID- 9529878
TI  - Pharmacokinetics for the MCH nurse.

PMID- 9529879
TI  - Managed care and physician referral.

PMID- 9529880
TI  - A comparison of hospital utilization by Medicaid and privately insured patients.

PMID- 9529881
TI  - Does dissatisfaction with access to specialists affect the desire to leave a
      managed care plan?

PMID- 9529882
TI  - Medicaid HMO enrollees in the emergency room: use of nonemergency care.

PMID- 9529883
TI  - Cost-effectiveness of detecting breast cancer in lower socioeconomic status
      African American and Hispanic women through mobile mammography services.

PMID- 9529884
TI  - The geographic distribution of physicians in the United States and the
      contribution of international medical graduates.

PMID- 9529885
TI  - Major facilitator superfamily.
AB  - The major facilitator superfamily (MFS) is one of the two largest families of
      membrane transporters found on Earth. It is present ubiquitously in bacteria,
      archaea, and eukarya and includes members that can function by solute uniport,
      solute/cation symport, solute/cation antiport and/or solute/solute antiport with
      inwardly and/or outwardly directed polarity. All homologous MFS protein sequences
      in the public databases as of January 1997 were identified on the basis of
      sequence similarity and shown to be homologous. Phylogenetic analyses revealed
      the occurrence of 17 distinct families within the MFS, each of which generally
      transports a single class of compounds. Compounds transported by MFS permeases
      include simple sugars, oligosaccharides, inositols, drugs, amino acids,
      nucleosides, organophosphate esters, Krebs cycle metabolites, and a large variety
      of organic and inorganic anions and cations. Protein members of some MFS families
      are found exclusively in bacteria or in eukaryotes, but others are found in
      bacteria, archaea, and eukaryotes. All permeases of the MFS possess either 12 or
      14 putative or established transmembrane alpha-helical spanners, and evidence is
      presented substantiating the proposal that an internal tandem gene duplication
      event gave rise to a primordial MFS protein prior to divergence of the family
      members. All 17 families are shown to exhibit the common feature of a well
      conserved motif present between transmembrane spanners 2 and 3. The analyses
      reported serve to characterize one of the largest and most diverse families of
      transport proteins found in living organisms.

PMID- 9529886
TI  - Asexual sporulation in Aspergillus nidulans.
AB  - The formation of mitotically derived spores, called conidia, is a common
      reproductive mode in filamentous fungi, particularly among the large fungal class
      Ascomycetes. Asexual sporulation strategies are nearly as varied as fungal
      species; however, the formation of conidiophores, specialized multicellular
      reproductive structures, by the filamentous fungus Aspergillus nidulans has
      emerged as the leading model for understanding the mechanisms that control fungal
      sporulation. Initiation of A. nidulans conidiophore formation can occur either as
      a programmed event in the life cycle in response to intrinsic signals or to
      environmental stresses such as nutrient deprivation. In either case, a
      development-specific set of transcription factors is activated and these control
      the expression of each other as well as genes required for conidiophore
      morphogenesis. Recent progress has identified many of the earliest-acting genes
      needed for initiating conidiophore development and shown that there are at least
      two antagonistic signaling pathways that control this process. One pathway is
      modulated by a heterotrimeric G protein that when activated stimulates growth and
      represses both asexual and sexual sporulation as well as production of the toxic
      secondary metabolite, sterigmatocystin. The second pathway apparently requires an
      extracellular signal to induce sporulation-specific events and to direct the
      inactivation of the first pathway, removing developmental repression. A working
      model is presented in which the regulatory interactions between these two
      pathways during the fungal life cycle determine whether cells grow or develop.

PMID- 9529887
TI  - Molecular genetics of mating recognition in basidiomycete fungi.
AB  - The recognition of compatible mating partners in the basidiomycete fungi requires
      the coordinated activities of two gene complexes defined as the mating-type
      genes. One complex encodes members of the homeobox family of transcription
      factors, which heterodimerize on mating to generate an active transcription
      regulator. The other complex encodes peptide pheromones and 7-transmembrane
      receptors that permit intercellular signalling. Remarkably, a single species may
      have many thousands of cross-compatible mating types because the mating-type
      genes are multiallelic. Different alleles of both sets of genes are necessary for
      mating compatibility, and they trigger the initial stages of sexual development-
      the formation of a specialized filamentous mycelium termed the dikaryon, in which
      the haploid nuclei remain closely associated in each cell but do not fuse. Three
      species have been taken as models to describe the molecular structure and
      organization of the mating-type loci and the genes sequestered within them: the
      pathogenic smut fungus Ustilago maydis and the mushrooms Coprinus cinereus and
      Schizophyllum commune. Topics addressed in this review are the roles of the
      mating-type gene products in regulating sexual development, the molecular basis
      for multiple mating types, and the molecular interactions that permit different
      allelic products of the mating type genes to be discriminated. Attention is drawn
      to the remarkable conservation in the mechanisms that regulate sexual development
      in basidiomycetes and unicellular ascomycete yeasts, Saccharomyces cerevisiae and
      Schizosaccharomyces pombe, a theme which is developed in the general conclusion
      to include the filamentous ascomycetes Neurospora crassa and Podospora anserina.

PMID- 9529889
TI  - Morphogenesis of Escherichia coli.
AB  - The shape of Escherichia coli is strikingly simple compared to those of higher
      eukaryotes. In fact, the end result of E. coli morphogenesis is a cylindrical
      tube with hemispherical caps. It is argued that physical principles affect
      biological forms. In this view, genes code for products that contribute to the
      production of suitable structures for physical factors to act upon. After
      introduction of a physical model, the discussion is focused on the shape
      maintaining (peptidoglycan) layer of E. coli. This is followed by a detailed
      analysis of the structural relationship of the cellular interior to the
      cytoplasmic membrane. A basic theme of this review is that the transcriptionally
      active nucleoid and the cytoplasmic translation machinery form a structural
      continuity with the growing cellular envelope. An attempt has been made to show
      how this dynamic relationship during the cell cycle affects cell polarity and how
      it leads to cell division.

PMID- 9529891
TI  - Growth of the stress-bearing and shape-maintaining murein sacculus of Escherichia
      coli.
AB  - To withstand the high intracellular pressure, the cell wall of most bacteria is
      stabilized by a unique cross-linked biopolymer called murein or peptidoglycan. It
      is made of glycan strands [poly-(GlcNAc-MurNAc)], which are linked by short
      peptides to form a covalently closed net. Completely surrounding the cell, the
      murein represents a kind of bacterial exoskeleton known as the murein sacculus.
      Not only does the sacculus endow bacteria with mechanical stability, but in
      addition it maintains the specific shape of the cell. Enlargement and division of
      the murein sacculus is a prerequisite for growth of the bacterium. Two groups of
      enzymes, hydrolases and synthases, have to cooperate to allow the insertion of
      new subunits into the murein net. The action of these enzymes must be well
      coordinated to guarantee growth of the stress-bearing sacculus without risking
      bacteriolysis. Protein-protein interaction studies suggest that this is
      accomplished by the formation of a multienzyme complex, a murein-synthesizing
      machinery combining murein hydrolases and synthases. Enlargement of both the
      multilayered murein of gram-positive and the thin, single-layered murein of gram
      negative bacteria seems to follow an inside-to-outside growth strategy. New
      material is hooked in a relaxed state underneath the stress-bearing sacculus
      before it becomes inserted upon cleavage of covalent bonds in the layer(s) under
      tension. A model is presented that postulates that maintenance of bacterial shape
      is achieved by the enzyme complex copying the preexisting murein sacculus that
      plays the role of a template.

PMID- 9529894
TI  - AHEC students "try on" rural practice.

PMID- 9529888
TI  - Oral microbial ecology and the role of salivary immunoglobulin A.
AB  - In the oral cavity, indigenous bacteria are often associated with two major oral
      diseases, caries and periodontal diseases. These diseases seem to appear
      following an imbalance in the oral resident microbiota, leading to the emergence
      of potentially pathogenic bacteria. To define the process involved in caries and
      periodontal diseases, it is necessary to understand the ecology of the oral
      cavity and to identify the factors responsible for the transition of the oral
      microbiota from a commensal to a pathogenic relationship with the host. The
      regulatory forces influencing the oral ecosystem can be divided into three major
      categories: host related, microbe related, and external factors. Among host
      factors, secretory immunoglobulin A (SIgA) constitutes the main specific immune
      defense mechanism in saliva and may play an important role in the homeostasis of
      the oral microbiota. Naturally occurring SIgA antibodies that are reactive
      against a variety of indigenous bacteria are detectable in saliva. These
      antibodies may control the oral microbiota by reducing the adherence of bacteria
      to the oral mucosa and teeth. It is thought that protection against bacterial
      etiologic agents of caries and periodontal diseases could be conferred by the
      induction of SIgA antibodies via the stimulation of the mucosal immune system.
      However, elucidation of the role of the SIgA immune system in controlling the
      oral indigenous microbiota is a prerequisite for the development of effective
      vaccines against these diseases. The role of SIgA antibodies in the acquisition
      and the regulation of the indigenous microbiota is still controversial. Our
      review discusses the importance of SIgA among the multiple factors that control
      the oral microbiota. It describes the oral ecosystems, the principal factors that
      may control the oral microbiota, a basic knowledge of the secretory immune
      system, the biological functions of SIgA, and, finally, experiments related to
      the role of SIgA in oral microbial ecology.

PMID- 9529895
TI  - The brave New World of quantum health care: some further thoughts on the
      physician culture. Part II.

PMID- 9529896
TI  - The management of patients with attention-deficit hyperactivity disorder by
      family practitioners.
AB  - BACKGROUND: The objective of this study was to describe the practices of family
      practitioners in Missouri in the treatment of patients with ADHD. METHOD: The 634
      Diplomats of the American Board of Family Practice of Missouri were surveyed.
      RESULTS: Respondents considered stimulant medication to be effective treatment
      for ADHD; methylphenidate was the drug of choice. Most respondents (79%) reported
      recommending behavioral management to parents. Reported efficacy of stimulants
      (item 2) and use of behavior management (item 8) were related in the negative
      direction, while reported efficacy of stimulants and using stimulants alone (item
      13) were related in the positive direction. CONCLUSIONS: Family practitioners in
      Missouri used accepted treatments for ADHD, but in general, practices were not
      entirely consistent with the current standard of care. Physicians' belief in the
      efficacy of stimulants may have prejudiced them against multimodal treatment.

PMID- 9529897
TI  - Emergency medicine quiz #4. Ludwig's angina. Upper airway obstruction.

PMID- 9529898
TI  - Legal and ethical implications for physicians who treat their own employees.

PMID- 9529899
TI  - Lycopene: chemistry, biology, and implications for human health and disease.
AB  - A diet rich in carotenoid-containing foods is associated with a number of health
      benefits. Lycopene provides the familiar red color to tomato products and is one
      of the major carotenoids in the diet of North Americans and Europeans. Interest
      in lycopene is growing rapidly following the recent publication of epidemiologic
      studies implicating lycopene in the prevention of cardiovascular disease and
      cancers of the prostate or gastrointestinal tract. Lycopene has unique structural
      and chemical features that may contribute to specific biological properties. Data
      concerning lycopene bioavailability, tissue distribution, metabolism, excretion,
      and biological actions in experimental animals and humans are beginning to
      accumulate although much additional research is necessary. This review will
      summarize our knowledge in these areas as well as the associations between
      lycopene consumption and human health.

PMID- 9529893
TI  - Vacuole biogenesis in Saccharomyces cerevisiae: protein transport pathways to the
      yeast vacuole.
AB  - Delivery of proteins to the vacuole of the yeast Saccharomyces cerevisiae
      provides an excellent model system in which to study vacuole and lysosome
      biogenesis and membrane traffic. This organelle receives proteins from a number
      of different routes, including proteins sorted away from the secretory pathway at
      the Golgi apparatus and endocytic traffic arising from the plasma membrane.
      Genetic analysis has revealed at least 60 genes involved in vacuolar protein
      sorting, numerous components of a novel cytoplasm-to-vacuole transport pathway,
      and a large number of proteins required for autophagy. Cell biological and
      biochemical studies have provided important molecular insights into the various
      protein delivery pathways to the yeast vacuole. This review describes the various
      pathways to the vacuole and illustrates how they are related to one another in
      the vacuolar network of S. cerevisiae.

PMID- 9529900
TI  - Gastrointestinal alcohol dehydrogenase.
AB  - Alcohol dehydrogenase (ADH) consists of a family of isozymes that convert
      alcohols to their corresponding aldehydes using NAD+ as a cofactor. The
      metabolism of ethanol by gastrointestinal ADH isozymes results in the production
      of acetaldehyde, a highly toxic compound that binds to cellular protein and DNA
      if not further metabolized to acetate by acetaldehyde dehydrogenase isozymes.
      Acetaldehyde seems to be involved in ethanol-associated cocarcinogenesis. The
      metabolism of retinol and the generation of retinoic acid is a function of class
      I and class IV ADH, and its inhibition by alcohol may lead to an alteration of
      epithelial cell differentiation and cell growth and may also be involved in
      ethanol-associated gastrointestinal cocarcinogenesis.

PMID- 9529901
TI  - Fatty acids bind directly to and activate peroxisome proliferator-activated
      receptors alpha and gamma.
AB  - Peroxisome proliferator-activated receptors alpha and gamma function in lipid
      homeostasis. The receptors are activated by direct binding of hypolipidemic drugs
      and of mono- and polyunsaturated fatty acids. Upon activation, these receptors
      interact with a number of different genes involved in lipid metabolism.

PMID- 9529902
TI  - Divided attention between simultaneous auditory and visual signals.
AB  - Past studies of simultaneous attention to pairs of visual stimuli have used the
      "dual-task" paradigm to show that identification of the direction of a change in
      luminance, whether incremental or decremental, is "capacity-limited," while
      simple detection of these changes is governed by "capacity-free" processes. On
      the basis of that finding, it has been suggested that the contrast between
      identification and detection reflects different processes in the sensory
      periphery, namely the responses of magno- and parvocellular receptors. The
      present study questions that assertion and investigates the contribution of
      central processing in resource limitation by applying the dual task to a
      situation in which one stimulus is auditory and one is visual. The results are
      much the same as before, with identification demonstrating the tradeoff in
      performance generally attributed to a limited capacity but detection showing no
      loss compared with single-task controls. This implies that limitations on
      resources operate at a central level of processing rather than in the auditory
      and visual peripheries.

PMID- 9529903
TI  - Simultaneous encoding of direction at a local and global scale.
AB  - Human observers can simultaneously encode direction information at two different
      scales, one local (an individual dot) and one global (the coherent motion of a
      field of dots distributed over a 10 degrees-diameter display). We assessed
      whether encoding global motion would preclude the encoding of a local trajectory
      component and vice versa. In the present experiments, a large number (100-150) of
      dots were randomly assigned directions in each frame from a uniform distribution
      of directions spanning a range of 160 degrees to create global motion in a single
      direction (Williams & Sekuler, 1984). Amidst these background dots, 1 dot moved
      in a consistent direction (trajectory) for the duration of the display. The
      direction of this "trajectory dot" was similar to the mean direction of the
      distribution of directions determining the movement of the background dots.
      Direction discrimination for both the global motion and the trajectory was
      measured, using the method of constant stimuli, under precued and postcued
      partial report conditions. A low- or high-frequency 85-msec tone signaled which
      motion the subject was to judge. In the precue condition, the tone was presented
      200 msec before the onset of the stimulus, whereas in the postcue condition, the
      tone was presented immediately after the offset of the stimulus. Direction
      discrimination thresholds for both global and local motion in the postcued
      condition were not significantly different from those obtained in the precued
      condition. These results suggest that direction information for both global and
      local motion is encoded simultaneously and that the observer has access to either
      motion signal after the presentation of a stimulus.

PMID- 9529905
TI  - Spectral-motion aftereffects and the tritone paradox among Canadian subjects.
AB  - The effect of spectral motion on the tritone paradox was investigated by
      pretesting subjects residing in southwestern Ontario, Canada, on the tritone
      task, presenting them with a continuous ascending or descending chromatic scale
      created using Shepard tones, and then retesting them on the tritone task. Results
      indicated a negative-motion aftereffect that affected the orientation of the
      pitch class circle. Differential effects of perceived pitch height on the lower
      portion of the pitch class circle and of adaptation on the upper portion of the
      pitch class circle were found in the pre- and postadaptation data, respectively.
      The implications of this dissociation are discussed. In addition, since our
      subjects lived relatively close to the U.S. border, the experimental pretests
      allowed us to examine the hypothesis that a canonical American pitch template
      similar to that found among "Californian" subjects (Deutsch, 1991) is propagated
      by linguistic influences of media such as television and radio (Ragozzine &
      Deutsch, 1994). A survey of our subjects indicated that overall, the majority of
      time engaged in listening to the radio and watching television or movies was
      spent with American sources. Despite this, and despite the fact that subjects had
      widely varying language and cultural backgrounds, a tight distribution of peak
      pitch classes was found that is indicative of a "British" pitch template
      (Deutsch, 1991) for every subject tested.

PMID- 9529904
TI  - Fixation point offsets facilitate endogenous saccades.
AB  - Subjects produced saccades to continuously visible targets that were signaled by
      the pitch, not the location, of an auditory signal. Such endogenous saccades were
      initiated more quickly when the visual fixation point disappeared 200 msec before
      the signal (thus producing a "gap"), even though the alerting benefits of such a
      warning were eliminated by an earlier warning tone. The presence of the gap
      effect under these circumstances shows that the effect is more general than was
      previously believed: Visual fixation point offsets facilitate saccades by
      affecting oculomotor processes related to both visually elicited (exogenous) and
      centrally produced (endogenous) saccades. In addition, the magnitude of the gap
      effect for endogenous saccades was significantly smaller than that for exogenous
      saccades, suggesting that at least some of the effect arises in relatively early
      processes, such as those involved in the processing of sensory signals, and not
      exclusively in later processes, such as those involved in the preparation and
      production of saccades.

PMID- 9529906
TI  - The McCollough effect across the menstrual cycle.
AB  - The McCollough effect (ME) has been shown to be sensitive to cholinergic agents,
      being strengthened by hyoscine (antagonist) and weakened by physostigmine
      (agonist), and possibly to more generalized changes in CNS arousal. We therefore
      expected the ME to be sensitive to hormonal changes during the menstrual cycle,
      being strongest in the postovulatory phases when arousal is low. In two
      experiments we found a highly significant effect of menstrual phase for the
      normally cycling women, but not for oral contraceptive users: ME strength
      gradually increased across the cycle, reaching a premenstrual peak. These
      findings may be explained in terms of hormonally mediated changes in arousal
      across the menstrual cycle.

PMID- 9529892
TI  - Maltose/maltodextrin system of Escherichia coli: transport, metabolism, and
      regulation.
AB  - The maltose system of Escherichia coli offers an unusually rich set of enzymes,
      transporters, and regulators as objects of study. This system is responsible for
      the uptake and metabolism of glucose polymers (maltodextrins), which must be a
      preferred class of nutrients for E. coli in both mammalian hosts and in the
      environment. Because the metabolism of glucose polymers must be coordinated with
      both the anabolic and catabolic uses of glucose and glycogen, an intricate set of
      regulatory mechanisms controls the expression of mal genes, the activity of the
      maltose transporter, and the activities of the maltose/maltodextrin catabolic
      enzymes. The ease of isolating many of the mal gene products has contributed
      greatly to the understanding of the structures and functions of several classes
      of proteins. Not only was the outer membrane maltoporin, LamB, or the phage
      lambda receptor, the first virus receptor to be isolated, but also its three
      dimensional structure, together with extensive knowledge of functional sites for
      ligand binding as well as for phage lambda binding, has led to a relatively
      complete description of this sugar-specific aqueous channel. The periplasmic
      maltose binding protein (MBP) has been studied with respect to its role in both
      maltose transport and maltose taxis. Again, the combination of structural and
      functional information has led to a significant understanding of how this soluble
      receptor participates in signaling the presence of sugar to the chemosensory
      apparatus as well as how it participates in sugar transport. The maltose
      transporter belongs to the ATP binding cassette family, and although its
      structure is not yet known at atomic resolution, there is some insight into the
      structures of several functional sites, including those that are involved in
      interactions with MBP and recognition of substrates and ATP. A particularly
      astonishing discovery is the direct participation of the transporter in
      transcriptional control of the mal regulon. The MalT protein activates
      transcription at all mal promoters. A subset also requires the cyclic AMP
      receptor protein for transcription. The MalT protein requires maltotriose and ATP
      as ligands for binding to a dodecanucleotide MalT box that appears in multiple
      copies upstream of all mal promoters. Recent data indicate that the ATP binding
      cassette transporter subunit MalK can directly inhibit MalT when the transporter
      is inactive due to the absence of substrate. Despite this wealth of knowledge,
      there are still basic issues that require clarification concerning the mechanism
      of MalT-mediated activation, repression by the transporter, biosynthesis and
      assembly of the outer membrane and inner membrane transporter proteins, and
      interrelationships between the mal enzymes and those of glucose and glycogen
      metabolism.

PMID- 9529907
TI  - Attentional processing of "unattended" flankers: evidence for a failure of
      selective attention.
AB  - Results from research with the flanker task have been used to argue both that
      flankers are identified without attention and that flanker identification
      requires attention. In three experiments, we addressed this issue by examining
      flanker recall. In Experiment 1, we manipulated flanker redundancy, a variable
      that could influence attention to the flankers, in order to determine whether it
      affected the magnitude of the flanker effect, the magnitude of flanker recall, or
      both. Redundancy did not influence the flanker effect, and recall was high in
      both conditions, suggesting that the flankers were attended. The recall results
      contradicted those of Miller (1987), the only other study that we could find in
      which flanker recall was used. In Experiments 2 and 3, we examined differences
      between Miller's procedure and ours. Although flanker recall was lower when open
      ended rather than forced recall was used and when the flanker task was made more
      complicated, flanker recall remained well above chance in all conditions. The
      data strongly suggest that in the typical correlated flanker task there is a
      failure of selective attention at some point during processing such that flankers
      receive attentional processing.

PMID- 9529908
TI  - Conjoining auditory and visual features during high-rate serial presentation:
      processing and conjoining two features can be faster than processing one.
AB  - The time required to conjoin stimulus features in high-rate serial presentation
      tasks was estimated in auditory and visual modalities. In the visual experiment,
      targets were defined by color, orientation, or the conjunction of color and
      orientation features. Responses were fastest in color conditions, intermediate in
      orientation conditions, and slowest in conjunction conditions. Estimates of
      feature conjunction time (FCT) were derived on the basis of a model in which
      features were processed in parallel and then conjoined, permitting FCTs to be
      estimated from the difference in reaction times between conjunction and the
      slowest single-feature condition. Visual FCTs averaged 17 msec, but were negative
      for certain stimuli and subjects. In the auditory experiment, targets were
      defined by frequency, location, or the conjunction of frequency and location
      features. Responses were fastest in frequency conditions, but were faster in
      conjunction than in location conditions, yielding negative FCTs. The results from
      both experiments suggest that the processing of stimulus features occurs
      interactively during early stages of feature conjunction.

PMID- 9529909
TI  - The mean-integral representation of rectangles.
AB  - To assess perceptual interaction between the height and width of rectangles, we
      used an accuracy variant of the Garner paradigm. We measured the discriminability
      of height and width (baseline tasks) and size and shape (correlated tasks). From
      the d' values in these conditions, we estimated perceptual distances and inferred
      a mean-integral representation in which height and width corresponded to non
      independent dimensions in a perceptual space. This model accounted well for
      performance in these two-stimulus conditions, and it also explained 70%-80% of
      the decline in performance in selective and divided attention. In a second
      experiment, conducted for purposes of comparison with the rectangle
      discrimination Experiment, we studied the discrimination of horizontal and
      vertical line segments connected in an L-shape. In size discrimination, observers
      were equally good with line pairs and rectangles, suggesting holistic perception;
      but in shape discrimination, they appeared to combine information from the two
      line-pair components of the rectangle independently. The mean-integral model was
      again successful in relating performance in the Garner tasks quantitatively.

PMID- 9529910
TI  - Masked repetition and phonological priming in picture naming.
AB  - We report a series of picture naming experiments in which target pictures were
      primed by briefly presented masked words. Experiment 1 demonstrates that the
      prior presentation of the same word prime (e.g., rose-ROSE) facilitates picture
      naming independently of the target's name frequency. In Experiment 2, primes that
      were homophones of picture targets (e.g., rows-ROSE) also produced facilitatory
      effects compared with unrelated controls, but priming was significantly larger
      for targets with low-frequency names relative to targets with high-frequency
      names. In Experiment 3, primes that were higher frequency homophones of picture
      targets produced facilitatory effects compared with identical primes. These
      results are discussed in relation to different accounts of the effects of masked
      priming in current models of picture naming.

PMID- 9529911
TI  - Visual inertia of rotating 3-D objects.
AB  - Five experiments were designed to determine whether a rotating, transparent 3-D
      cloud of dots (simulated sphere) could influence the perceived direction of
      rotation of a subsequent sphere. Experiment 1 established conditions under which
      the direction of rotation of a virtual sphere was perceived unambiguously. When a
      near-far luminance difference and perspective depth cues were present, observers
      consistently saw the sphere rotate in the intended direction. In Experiment 2, a
      near-far luminance difference was used to create an unambiguous rotation sequence
      that was followed by a directionally ambiguous rotation sequence that lacked both
      the near-far luminance cue and the perspective cue. Observers consistently saw
      the second sequence as rotating in the same direction as the first, indicating
      the presence of 3-D visual inertia. Experiment 3 showed that 3-D visual inertia
      was sufficiently powerful to bias the perceived direction of a rotation sequence
      made unambiguous by a near-far luminance cue. Experiment 5 showed that 3-D visual
      inertia could be obtained using an occlusion depth cue to create an unambiguous
      inertia-inducing sequence. Finally, Experiments 2, 4, and 5 all revealed a fast
      decay phase of inertia that lasted for approximately 800 msec, followed by an
      asymptotic phase that lasted for periods as long as 1,600 msec. The implications
      of these findings are examined with respect to motion mechanisms of 3-D visual
      inertia.

PMID- 9529890
TI  - Cell wall and secreted proteins of Candida albicans: identification, function,
      and expression.
AB  - The cell wall is essential to nearly every aspect of the biology and
      pathogenicity of Candida albicans. Although it was initially considered an almost
      inert cellular structure that protected the protoplast against osmotic offense,
      more recent studies have demonstrated that it is a dynamic organelle. The major
      components of the cell wall are glucan and chitin, which are associated with
      structural rigidity, and mannoproteins. The protein component, including both
      mannoprotein and nonmannoproteins, comprises some 40 or more moieties. Wall
      proteins may differ in their expression, secretion, or topological location
      within the wall structure. Proteins may be modified by glycosylation (primarily
      addition of mannose residues), phosphorylation, and ubiquitination. Among the
      secreted enzymes are those that are postulated to have substrates within the cell
      wall and those that find substrates in the extracellular environment. Cell wall
      proteins have been implicated in adhesion to host tissues and ligands.
      Fibrinogen, complement fragments, and several extracellular matrix components are
      among the host proteins bound by cell wall proteins. Proteins related to the
      hsp70 and hsp90 families of conserved stress proteins and some glycolytic enzyme
      proteins are also found in the cell wall, apparently as bona fide components. In
      addition, the expression of some proteins is associated with the morphological
      growth form of the fungus and may play a role in morphogenesis. Finally, surface
      mannoproteins are strong immunogens that trigger and modulate the host immune
      response during candidiasis.

PMID- 9529912
TI  - The role of head-centric spatial reference with a static and kinetic visual
      disturbance.
AB  - A static or kinetic visual disturbance affects subjects' ability to estimate the
      direction of the gravitational vertical. This kind of error is increased by a
      head roll inclination. In two experiments, we combined head orientation with a
      static (Experiment 1: tilted frame) versus kinetic (Experiment 2: rotating disk)
      visual disturbance. The results showed that with a static visual disturbance, the
      increase of errors in the inclined head condition was mainly the consequence of a
      postural head effect like an Aubert effect. On the contrary, with a kinetic
      visual disturbance, it appears that the disk effect increases with head
      inclination. However, individual errors observed with the head inclined in front
      of a stationary disk were systematically correlated with the errors triggered by
      the same head inclination in front of a rotating disk. These observations confirm
      that the head axis spatial reference plays an important role in orientation
      perception, whatever the head position and the kind of visual display.

PMID- 9529913
TI  - Inhibitory processes in auditory selective attention: evidence of location-based
      and frequency-based inhibition of return.
AB  - The possibility that there is an inhibitory component to auditory covert
      orienting was addressed. Each trial consisted of a cue followed by a target, and
      listeners were required to detect, localize, or identify the frequency of the
      target. At 150-msec stimulus onset asynchrony (SOA), performance was best when
      stimuli sounded from the same location or were of the same frequency. However, at
      750-msec SOA, performance was best when stimuli differed in location or were of
      different frequencies. These results document the existence of both location
      based and frequency-based auditory inhibition of return.

PMID- 9529914
TI  - The recovery of identity and relative position from visual input: further
      evidence for the independence of processing of what and where.
AB  - Four experiments examined the manner in which item identity and relative position
      are recovered from visual input. A successive same/different matching paradigm
      was designed in which each trial contained a prime and a target display. Each
      display contained a reference object (i.e., a "+") and a located object (i.e., a
      letter, which fell to either the right or the left of the "+"). In Experiment 1,
      subjects carried out identity judgments on the letters. Experiments 2 examined
      relative position judgments; in Experiment 3, subjects had to judge both item
      identity and relative position information. Overall, these initial data suggested
      that identity and positional information are recovered via independent mechanisms
      and that these operate concurrently. This suggestion was supported by the results
      of Experiment 4, which in turn disconfirmed an alternative response account of
      performance.

PMID- 9529915
TI  - Judgments of the duration of visually marked empty time intervals: linking
      perceived duration and sensitivity.
AB  - The capability of subjects to categorize (as short or long) visually marked empty
      time intervals was investigated in three experiments. Two visual signals, located
      18 degrees to the left (L) and to the right (R) of a fixation point in the visual
      field, established four marking conditions, two unilaterally presented (L-L and R
      R) and two bilaterally presented (L-R and R-L). In Experiments 1 and 2, the
      results show that discrimination is better with unilateral sequences than with
      bilateral sequences and that the perceived duration is longer with an L-R than
      with an R-L sequence. In addition, Experiment 2 shows that, in comparison with a
      condition in which Markers 1 and 2 remain identical for a complete session,
      varying the markers from trial to trial does not decrease discrimination. Also,
      Experiment 2 shows that discrimination is better when both visual markers are
      presented at fovea than it is in the unilateral conditions. Experiment 3 shows
      that bilateral intervals are perceived as being longer and are better
      discriminated than are intervals marked by an intermodal sequence (auditory
      visual or visual-auditory). The general discussion reports the implications of
      having different perceived duration and sensitivity levels, in various marker
      type conditions, for an internal-clock hypothesis. Some implications of these
      results for a lateralized-timer hypothesis are also discussed.

PMID- 9529916
TI  - Apparent body tilt and postural aftereffect.
AB  - Apparent orientation of the body tilted laterally in the frontal plane was
      studied with the methods of absolute judgments in four experiments. In Experiment
      1, 17 subjects, who maintained the normal adaptation of body to gravity,
      estimated their body tilts under the condition of seeing the gravitational
      vertical and under the condition of eliminating it. The results showed that (1)
      there was not a significant difference between the two conditions and (2) the
      small tilts of less than 45 degrees were exactly estimated, whereas the large
      tilts of 45 degrees-108 degrees were overestimated. In Experiment 2, 10 subjects
      estimated their body tilts under three velocities of a rotating chair on which
      each subject was placed. Although both body tilt and chair velocity were found to
      influence tilt estimation, the effect of body tilt was overwhelmingly greater
      than that of chair velocity. In Experiment 3, 11 subjects adapted their bodies to
      a 72 degrees left tilt for 10 min and then estimated various body tilts around
      the adapting tilt. The estimations obtained under the 72 degrees adaptation were
      lower than those obtained under the 0 degree adaptation, and this reduction was
      greater for the test tilt that was farther away from the adapting tilt. In
      Experiment 4, 11 subjects adjusted their own body tilts to designated angles. The
      results confirmed the outcomes of absolute estimation in Experiments 1-3. From
      these findings and past literature, the judgments of body tilt were considered to
      be subserved by a single sensory process that was based on the cutaneous and
      muscular proprioceptors, rather than the vestibular and joint proprioceptors.

PMID- 9529917
TI  - Deciding about death: physician-assisted suicide and the courts--a panel
      discussion.

PMID- 9529918
TI  - Cinema's disillusioned physician: Akira Kurosawa's red beard and Ingmar Bergman's
      Wild Strawberries.

PMID- 9529919
TI  - Occasion sudden.

PMID- 9529920
TI  - Prague's season of discontent.

PMID- 9529921
TI  - Dr. Stead on doctoring: advice to emerging physicians. Interview by S. Gray
      Hughes, Galen S. Wagner, and Mark W. Swaim.

PMID- 9529922
TI  - Therapeutic uses for cocaine: a historical review.

PMID- 9529923
TI  - Why emulate great medical leaders: what do such leaders teach?

PMID- 9529924
TI  - The business of medicine: the professionalization/commercialization boundary in
      nineteenth-century medical practice.

PMID- 9529925
TI  - Good clinical teachers: created by nature, or nature?

PMID- 9529926
TI  - Analysis of 200 consecutive neuropathologically verified brain tumors of
      childhood.
AB  - Brain tumors are the most frequent solid neoplasms of childhood. We present here
      a series of 200 consecutive cases of neuropathologically verified brain tumors in
      children under 18, operated on between 1990-1996 at the Polish Mother Memorial
      Hospital in Lodz. The respective diagnoses were established on the basis of light
      microscopy, ultrastructure and immunohistochemistry. The criteria of the World
      Health Organization (WHO) classification of central nervous system (CNS) tumors
      were used in all but one (superficial desmoplastic cerebral astrocytoma of
      infancy) case. The location of tumors, age and sex of children and tumors'
      histology in our material were compared with those of previously published series
      of pediatric brain tumors.

PMID- 9529927
TI  - TP53 mutations in malignant astrocytomas.
AB  - Astrocytomas are the most common tumors of the central nervous system (CNS).
      Their malignant counterparts, anaplastic astrocytoma and glioblastoma, are lethal
      neoplasms with poor clinical outcome and they frequently carry mutations of TP53
      tumor suppressor gene. In order to determine the frequency and type of this
      molecular alteration in the Polish population, we analyzed the polymerase chain
      reaction products corresponding to the most conservative exons 5-8 for single
      strand conformation polymorphism and confirmed the presence of mutations by
      direct DNA sequencing. We identified mutations in one of five (20%) anaplastic
      astrocytomas and in eight of 28 (29%) glioblastomas; the mutations were most
      frequently identified in the exon 8 (six glioblastomas). The frequency of TP53
      mutations is thus similar to the corresponding data from other studies, and the
      type of mutations suggests the participation of endogenous etiological factor.

PMID- 9529928
TI  - Morphological studies of the lungs in chronic hypobaric hypoxia.
AB  - The aim of the present study was to evaluate the effect of hypobaric hypoxia on
      the changes observed within lung parenchyma, particularly in the surfactant
      system-forming structures. The experiment used male Wistar rats, 180-220g b.w.
      The animals were kept in a hypobaric chamber for 3, 10 and 30 days. Pressure in
      the chamber (380mm Hg) corresponded to air rarefaction at an altitude of 5500m.
      Control animals were kept in the same room near the chamber at normal atmospheric
      pressure. The changes observed in the lungs were evaluated basing on
      ultrastructural analysis by transmission electron microscopy. The present results
      indicate phasic character of the changes occurring within lung parenchyma,
      including the surfactant system-forming structures. In the early phase (3 days),
      destructive-exudative changes predominated (delamelation of type II pneumocytes;
      oedematous changes, damage to the alveolar lining layer, accumulation of alveolar
      macrophages). In the later phases, repair-proliferative processes were
      predominant (increased number of type II pneumocytes, focal intensification of
      fibroplasia). The changes within the surfactant system-forming structures were
      accompanied by the accumulation of granulocytes and monocytes (hypobaric
      conditions for 3 and 10 days) and blood platelets (hypobaric conditions for 30
      days) in the vascular bed of the lungs. The pathomechanism of the changes
      observed in the surfactant system was discussed with regard to the vascular
      changes. The possibility of formation of blood platelets within the vascular
      system of the lungs was considered.

PMID- 9529929
TI  - Complexity, dynamic cellular network, and tumorigenesis.
AB  - A holistic approach to tumorigenesis is proposed. The main element of the model
      is the existence of dynamic cellular network. This network comprises a molecular
      and an energetistic structure of a cell connected through the multidirectional
      flow of information. The interactions within dynamic cellular network are
      complex, stochastic, nonlinear, and also involve quantum effects. From this non
      reductionist perspective, neither tumorigenesis can be limited to the genetic
      aspect, nor the initial event must be of molecular nature, nor mutations and
      epigenetic factors are mutually exclusive, nor a link between cause and effect
      can be established. Due to complexity, an unstable stationary state of dynamic
      cellular network rather than a group of unrelated genes determines the phenotype
      of normal and transformed cells. This implies relativity of tumor suppressor
      genes and oncogenes. A bifurcation point is defined as an unstable state of
      dynamic cellular network leading to the other phenotype-stationary state. In
      particular, the bifurcation point may be determined by a change of expression of
      a single gene. Then, the gene is called bifurcation point gene. The unstable
      stationary state facilitates the chaotic dynamics. This may result in a fractal
      dimension of both normal and tumor tissues. The co-existence of chaotic dynamics
      and complexity is the essence of cellular processes and shapes differentiation,
      morphogenesis, and tumorigenesis. In consequence, tumorigenesis is a complex,
      unpredictable process driven by the interplay between self-organisation and
      selection.

PMID- 9529930
TI  - Epithelioid malignant peripheral nerve sheath tumour--case report.

PMID- 9529931
TI  - Giant-cell carcinoma of the uterine tube. A case report.
AB  - A case of an extremely rare cancer of the uterine tube in a 43 year old woman is
      reported. The tumor has been diagnosed as primary giant-cell carcinoma of the
      uterine tube.

PMID- 9529932
TI  - Analysis of contact mechanics for composite cushion knee joint replacements.
AB  - Recent research in the area of cushion form bearings for total joint replacements
      has primarily used thin, soft, elastomeric layers with similar elastic modulus to
      articular cartilage, bonded to rigid substrates. These are designed to promote
      the body's natural lubricants to separate the articulating surfaces and prevent
      wear. Applications to joint replacements have revealed that the abrupt change in
      stiffness between the soft layer and the rigid substrate and the relatively low
      strength of the interface resulted in high shear stresses and debonding of the
      soft layer from the substrate. The approach adopted in this study is to use
      components with a graded modulus or composite construction. The composite
      construction consists of a soft compliant layer of polyurethane and a second
      stiffer polyurethane layer thought to be rigid enough to mechanically interlock
      to a metallic tibial tray. In this composite structure the deformation of the
      more rigid polyurethane underlay may generally influence the stress distribution
      and deformation in the softer upper layer and at the interface between the two
      materials. A simple analysis technique is presented in the present study where
      the composite double layer was approximated as an equivalent modulus single
      layer. Single layer theory, which is readily available in the literature, can
      then be used to determine the contact parameters, including the maximum contact
      pressure and the contact radius, for the composite structure. By varying the
      layer thicknesses and material properties of both the soft surface layer and the
      stiffer structural support layer, the magnitudes and locations of stresses can be
      controlled. Results of a parametric stress analysis are presented to assist in
      the selection of the most appropriate composite layers for cushion knee designs.
      A 4 mm thick surface layer with an elastic modulus of 20 MPa and a 4 mm thick
      structural support layer with an elastic modulus of 1000 MPa were considered
      suitable for this application.

PMID- 9529933
TI  - The influence of articular surface incongruity on lubrication and contact
      pressure distribution of loaded synovial joints.
AB  - In the model intended for short-term loading (such as during the walking cycle)
      of a human synovial joint in the lower extremities, cartilage lubricated by
      Newtonian synovial fluid is considered to be incompressible elastic and
      subchondral bone is considered to be rigid. The model is non-diffusional, i.e. no
      interstitial fluid flow occurs across the articular surfaces. A simple plane
      strain case of the human ankle joint is considered. For high steady loading
      applied in the centre of the stationary tibial arc and for steady sliding of the
      talar arc, this model shows that individual physiological variations in the
      geometry of the articular surfaces have only a small effect on the contact stress
      distribution and the fluid film thickness. If this load is applied eccentrically
      in the tibial arc, the contact pressure distribution varies more with surface
      geometry, but the minimum fluid film thickness differs little from that for
      symmetric loading. The maximum contact pressure is placed eccentrically in this
      case, but its value is changed only little when compared to the central loading
      of the same value. In order to explain different distribution patterns of
      subchondral bone mineralization, it is anticipated that the total load peaks of
      periodic time-dependent loads are transmitted centrally in some incongruent
      joints and eccentrically in others.

PMID- 9529934
TI  - Adaptive multimode lubrication in natural synovial joints and artificial joints.
AB  - To examine the lubrication mechanisms in both natural synovial joints and
      artificial joints with artificial cartilages, pendulum tests of pig shoulder
      joints and simulator tests of sliding pairs of a stainless steel spherical
      component and natural articular cartilage or artificial cartilage have been
      conducted. Firstly, it was shown in pendulum tests of pig shoulder joints that
      both concentration of hyaluronic acid or viscosity and adsorbed film formation of
      proteins and phospholipids exerted a significant effect on frictional behaviour
      in swinging motion immediately after a loading of 100 N. Under a high load of 1
      kN, low friction was observed under wide-ranging viscosity conditions, since a
      high load similar to body weight probably enhanced the squeeze film effect due to
      improved congruity. Next, frictional behaviour of sliding pairs in knee joint
      models, consisting of a stainless steel spherical surface and either specimens of
      pig tibial cartilage or polyvinylalcohol (PVA) hydrogel, was examined during
      walking in simulator tests. In these tests, the influences of lubricant viscosity
      and addition of protein on frictional behaviour were evaluated. For both
      compliant materials, the appropriate addition of gamma-globulin to sodium
      hyaluronate (HA) solution maintained low friction and protected rubbing surfaces
      under thin film conditions. These phenomena are discussed from the viewpoint of
      adaptive multimode lubrication.

PMID- 9529935
TI  - The yielding of tensioned fine wires in the Ilizarov frame.
AB  - The Ilizarov frame uses tensioned fine wires to support bone fragments. The
      objective of this study was to determine whether these wires deformed plastically
      under functional load bearing and to determine the significance of such
      deformation on the long-term performance of frames used for treating lower limb
      conditions. The mechanical characteristics of the wires were determined by means
      of destructive tensile tests and used in the construction of a series of finite
      element models replicating typical frame configurations. Each model was then
      subjected to a single load cycle representing a single step and the residual
      displacement (i.e. plastic deformation) was determined. In each case a residual
      displacement of between 0.26 and 0.42 mm was observed giving a corresponding
      reduction in wire tension of between 8.3 and 32.8 per cent. These reductions in
      wire tension reduce the frame's overall stiffness and so compromise its ability
      to inhibit high-amplitude axial and shear motions at the fracture site which are
      deleterious to the healing outcome.

PMID- 9529936
TI  - Prediction of plastic strains in ultra-high molecular weight polyethylene due to
      microscopic asperity interactions during sliding wear.
AB  - Studies of explanted femoral heads have shown that scratches caused by bone
      cement, bone or metallic particles are present on the rubbing surface. This
      damage has been cited as a cause of increased wear of ultra-high molecular weight
      polyethylene (UHMWPE) acetabular cups and it is known that the particulate wear
      debris produced leads to osteolysis. A series of explanted Charnley femoral heads
      have been surface characterized using a Talysurf 6 profilometer and found to have
      scratches with lip heights in the size range 0.1-3.25 microns with an average
      height of 1 micron giving an average aspect ratio (defined as height/half-width)
      of 0.1. These geometries were incorporated into a finite element model of a
      stainless steel asperity sliding over UHMWPE under conditions similar to those in
      an artificial hip system. It was found that as the aspect ratio of the asperity
      lip increased, the plastic strains both on and below the surface of the UHMWPE
      increased non-linearly, but that the magnitude of the strain was independent of
      the asperity height. The asperity aspect ratio was also found to affect the
      position of the maximum sub-surface strain, as the asperity aspect ratio was
      increased the maximum strain rose to the surface. The high plastic strains
      predicted offer an explanation for the highly elevated wear rates in scratched
      counterface tests and the aspect ratio of scratch lips is therefore a critical
      determinant of plastic strain.

PMID- 9529937
TI  - Discrepancy between penetration depths derived from radiographic and direct
      measurement of acetabular components.
AB  - The most common technique for assessing penetration due to wear in acetabular
      components is with the aid of the most recent serial radiograph. This approach,
      which is often termed the uni-radiographic method, has been shown to
      underestimate the more reliable value of the penetration depth deduced from
      direct measurement of explanted sockets. In this article the causes of the
      discrepancies between the two data sets are explored. Ninety-six sockets were
      available from revision surgery for which both the penetration depth and angle
      could be measured using the shadowgraphic technique in both the coronal and wear
      planes. Further, the penetration depth for each of the sockets was also assessed
      from pre-revision X-rays. A significant discrepancy was observed between the
      penetration depths measured in the wear plane of the replica delta Pw and that
      measured from the radiograph, delta PX-ray. The discrepancy was greatest for
      loose sockets as opposed to those that were still fixed at revision surgery.
      Using the corresponding data from the shadowgraph measurements, it was possible
      to deduce that the errors have arisen from the radiographic measurement of wear
      in the coronal plane and the formula used in calculating delta PX-ray. If these
      errors (which cannot be calculated from the X-ray data alone) were taken into
      consideration, then the systematic bias between radiographic and shadowgraphic
      measurement was greatly reduced. The largest portion of the discrepancy was
      accounted for by wear occurring out of the plane of the radiograph, and this, in
      general, coincides with the coronal plane. Overall, these results indicate that
      the accurate measurement of wear from serial radiographs is not possible and that
      improved performance in terms of accuracy can only be achieved when a three
      dimensional system is used. An alternative method for deducing the radiographic
      penetration depth is proposed which, theoretically, negates the error arising
      from the inaccuracy of the formula.

PMID- 9529938
TI  - Ultrasonic evaluation of ultra-high molecular weight polyethylene used in medical
      prostheses.
AB  - An ultrasonic non-destructive evaluation process is established to observe cracks
      and delaminations that occur below the surface of retrieved ultra-high molecular
      weight polyethylene joints. The result from the ultrasonic evaluation is compared
      with destructive (optical) test results of the actual cracks. Feasibility of
      characterizing different grades of bulk polyethylene is also established by means
      of ultrasonic attenuation measurements in the materials. This ultrasonic data can
      be used to give a better understanding of the failure mechanisms in the UHMWPE
      material.

PMID- 9529939
TI  - Wear of ultra-high molecular weight polyethylene acetabular cups in a
      physiological hip joint simulator in the anatomical position using bovine serum
      as a lubricant.

PMID- 9529940
TI  - Minding the body.
AB  - As we continue to elucidate relationships between neural structures and cognitive
      functioning in this Decade of the Brain, it is important not to lose sight of the
      larger context. The brain is but one component of the complex system that is the
      body. We take in information and interact with the world through our bodies, and
      our bodies change with--and in some cases change--cognitive and emotional
      processing. In this introductory paper, we present an overview of a broad range
      of psychophysiological techniques: electroencephalography, event-related
      potentials, magnetoencephalography, positron emission tomography, optical
      imaging, functional magnetic resonance imaging, electromyograms, eye tracking,
      pupillometry, cardiovascular measures, and electrodermal activity. These
      techniques not only differ in their temporal and spatial resolutions but also in
      the physiological and psychological processes to which they are sensitive. With
      respect to the system as a whole, these techniques are thus complementary.
      Combining measures--old and new, central and peripheral--ultimately provides the
      most inferential power for attacking the questions we hope to answer with all
      psychophysiological measures in our quest to understand the nature of the
      relationship between the mind and the body.

PMID- 9529941
TI  - Mental rotation of objects versus hands: neural mechanisms revealed by positron
      emission tomography.
AB  - Twelve right-handed men participated in two mental rotation tasks as their
      regional cerebral blood flow (rCBF) was monitored using positron emission
      tomography. In one task, participants mentally rotated and compared figures
      composed of angular branching forms; in the other task, participants mentally
      rotated and compared drawings of human hands. In both cases, rCBF was compared
      with a baseline condition that used identical stimuli and required the same
      comparison, but in which rotation was not required. Mental rotation of branching
      objects engendered activation in the parietal lobe and Area 19. In contrast,
      mental rotation of hands engendered activation in the precentral gyrus (M1),
      superior and inferior parietal lobes, primary visual cortex, insula, and frontal
      Areas 6 and 9. The results suggest that at least two different mechanisms can be
      used in mental rotation, one mechanism that recruits processes that prepare motor
      movements and another mechanism that does not.

PMID- 9529943
TI  - Cortical control of human classical conditioning: autonomic and positron emission
      tomography data.
AB  - A recent positron emission tomography (PET) study on brain mechanisms in
      classical, or Pavlovian, conditioning is reviewed. The PET data were compared
      with skin conductance data recorded off-line. The participants were five men who
      participated in three different experimental phases. In the first (habituation)
      phase, a tone was repeated 24 times at random intervals. In the second
      (acquisition) phase, the tone was paired with a brief shock to the wrist. In the
      third (extinction) phase, the tone was presented alone again. Statistical
      parametric mapping analysis of the PET data showed significantly increased
      activation of the right hemisphere in the orbitofrontal cortex, dorsolateral
      prefrontal cortex, inferior and superior frontal cortices, and inferior and
      middle temporal cortices. In the left hemisphere, only Area 19 and the superior
      frontal cortex showed significant activation. The findings are discussed within a
      theoretical framework that argues for different brain mechanisms in acquisition
      and extinction in classical conditioning.

PMID- 9529942
TI  - Relations between PET-derived measures of thalamic glucose metabolism and EEG
      alpha power.
AB  - Electroencephalogram (EEG) alpha power has been demonstrated to be inversely
      related to mental activity and has subsequently been used as an indirect measure
      of brain activation. The thalamus has been proposed as an important site for
      modulation of rhythmic alpha activity. Studies in animals have suggested that
      cortical alpha rhythms are correlated with alpha rhythms in the thalamus.
      However, little empirical evidence exists for this relation in humans. In the
      current study, resting EEG and a fluorodeoxyglucose positron emission tomography
      scan were measured during the same experimental session. Over a 30-min period,
      average EEG alpha power across 28 electrodes from 27 participants was robustly
      inversely correlated with glucose metabolic activity in the thalamus. These data
      provide the first evidence for a relation between alpha EEG power and thalamic
      activity in humans.

PMID- 9529944
TI  - Functional neuroanatomical correlates of electrodermal activity: a positron
      emission tomographic study.
AB  - To reveal areas in the central nervous system of importance for electrodermal
      control, regional cerebral blood flow (rCBF) was correlated to nonspecific skin
      conductance fluctuations (NSF) during aversive and nonaversive conditions.
      Participants viewed a TV screen displaying white noise or snake videotapes
      presented both with and without electric shocks given to the right hand. H2 15 O
      positron emission tomography was used to measure rCBF, and the constant voltage
      technique was used to measure NSF from the left hand. Electrodermal activity was
      positively related to rCBF in the left primary motor cortex (MI, Brodmann's Area
      4) and bilaterally in the anterior (Areas 24 and 32) and posterior cingulate
      cortex (Area 23). Negative relations were observed bilaterally in the secondary
      visual cortex (Areas 18 and 19) and the right inferior parietal cortex (Area 39),
      with a tendency also for the right insular cortex (Areas 13, 15, and 16). Because
      results from lesion and stimulation studies in humans converge with the present
      imaging results, we conclude that the cingulum and the motor cortex, in addition
      to the parietal and possibly the insular cortex, form part of one or several
      distributed neural network(s) involved in electrodermal control. Because these
      areas also support anticipation, affect, and locomotion, electrodermal responses
      seem to reflect cognitively or emotionally mediated motor preparation.

PMID- 9529945
TI  - Prefrontal cortex glucose metabolism and startle eyeblink modification
      abnormalities in unmedicated schizophrenia patients.
AB  - Attentional modulation of the startle reflex was studied in 16 unmedicated
      schizophrenia patients and 15 control individuals during the 18F-2-deoxyglucose
      uptake period for positron emission tomography. In a task involving attended,
      ignored, and novel tones that served as prepulses, control individuals showed
      greater prepulse inhibition (PPI) at 120 ms and greater prepulse facilitation at
      4,500 ms during attended than during ignored prepulses; the amount of PPI and
      facilitation during novel prepulses was intermediate. In contrast, patients
      failed to show differential PPI at 120 ms and tended to show greater facilitation
      at 4,500 ms during novel prepulses. For control individuals, greater PPI was
      associated with higher relative metabolic activity rates in prefrontal (Brodmann
      Areas 8, 9, and 10 bilaterally) and lower in visual cortex. Patients showed this
      relationship only for Area 10 on the left. Patients also had low metabolism in
      superior, middle, and inferior prefrontal cortex. Consistent with animal models,
      our results demonstrate the importance of the functional integrity of prefrontal
      cortex to PPI modulation.

PMID- 9529946
TI  - Emotional arousal and activation of the visual cortex: an fMRI analysis.
AB  - Functional activity in the visual cortex was assessed using functional magnetic
      resonance imaging technology while participants viewed a series of pleasant,
      neutral, or unpleasant pictures. Coronal images at four different locations in
      the occipital cortex were acquired during each of eight 12-s picture presentation
      periods (on) and 12-s interpicture interval (off). The extent of functional
      activation was larger in the right than the left hemisphere and larger in the
      occipital than in the occipitoparietal regions during processing of all picture
      contents compared with the interpicture intervals. More importantly, functional
      activity was significantly greater in all sampled brain regions when processing
      emotional (pleasant or unpleasant) pictures than when processing neutral stimuli.
      In Experiment 2, a hypothesis that these differences were an artifact of
      differential eye movements was ruled out. Whereas both emotional and neutral
      pictures produced activity centered on the calcarine fissure (Area 17), only
      emotional pictures also produced sizable clusters bilaterally in the occipital
      gyrus, in the right fusiform gyrus, and in the right inferior and superior
      parietal lobules.

PMID- 9529948
TI  - Ageing of the baby boomers--the future elderly.

PMID- 9529947
TI  - Processing of novel sounds and frequency changes in the human auditory cortex:
      magnetoencephalographic recordings.
AB  - Whole-head magnetoencephalographic (MEG) responses to repeating standard tones
      and to infrequent slightly higher deviant tones and complex novel sounds were
      recorded together with event-related brain potentials (ERPs). Deviant tones and
      novel sounds elicited the mismatch negativity (MMN) component of the ERP and its
      MEG counterpart (MMNm) both when the auditory stimuli were attended to and when
      they were ignored. MMNm generators were located bilateral to the superior planes
      of the temporal lobes where preattentive auditory discrimination appears to
      occur. A subsequent positive P3a component was elicited by deviant tones and with
      a larger amplitude by novel sounds even when the sounds were to be ignored.
      Source localization for the MEG counterpart of P3a (P3am) suggested that the
      auditory cortex in the superior temporal plane is involved in the neural network
      of involuntary attention switching to changes in the acoustic environment.

PMID- 9529949
TI  - The future demographic landscape of Singapore.

PMID- 9529950
TI  - The frail elderly in the family.
AB  - Longer life expectancy, better health and higher levels of financial independence
      will characterise the elderly of the future. These will result in a greater
      variety of living and care arrangements including an increasing proportion of
      older people who will choose to live on their own. Caring for a frail elderly
      person in the family requires a change of family roles, a process often
      accompanied by emotional upheavals. The degree of difficulty experienced will be
      linked to the level of economic and physical dependence of the elderly person.
      Demographic changes will add new dimensions to the problems of care. In four
      generation families, which will be more common, the burden of care will shift to
      adult grand children. Fewer children and grand-children will be available to
      share care responsibilities. A range of commercial and welfare services will be
      required to meet the increasing range of needs. Careful evaluation is needed in
      monitoring both improvements and the risks to the frail elderly and the family in
      the changing scenario.

PMID- 9529951
TI  - Housing Singapore's frail elderly in the next millennium.
AB  - This paper looks at the design of housing for an ageing population in the coming
      years, particularly the frail elderly, and at criteria which an architect would
      need to apply to provide for their social needs and various physical disabilities
      which may accompany old age. Recent local and overseas initiatives in providing
      special housing for elderly people are discussed and some proposals are made for
      more universal solutions, in the form of "lifetime homes".

PMID- 9529952
TI  - Future health issues and delivery needs of the elderly.
AB  - We have 6.9% of the population who are 65 years and older in June 1996. This
      figure will increase to 18.4% in 2030. In absolute numbers, the increase will be
      from 209,700 to 789,600 million in 2030. The majority of these however, will be
      ambulant and independent. Our important task in the health context is to help
      ageing persons maintain function and quality of life to achieve the maximum life
      span potential. To achieve this, we need to focus on individual preventive
      efforts to develop the medical profession in the new medicine paradigm, to
      provide care and we need to develop at the societal level the well network, the
      activating network and the health & nursing care network as an integrated
      seamless service. We also need at a societal level, to invest in the determinants
      of good health and disability-free life, namely, financial independence,
      acceptance by the family and recognition of the elderly, as valued members of
      society.

PMID- 9529953
TI  - Geriatric medicine: isn't there a better alternative?

PMID- 9529954
TI  - Epidemiology of falls among the elderly community dwellers in Singapore.
AB  - AIM: Falling is a serious medical problem for elderly persons. This study was
      done to look at prevalence and risk factors for falls in community dwelling
      elderly in Singapore. METHOD: A random sample of 3,000 persons aged 60 years and
      above was chosen from a database based on the 1990 population census. Letters
      were sent out to 2,582 subjects who had local and complete addresses. In the
      letter, they were informed about the purpose of the survey, and invited to
      participate in a questionnaire and clinical health screening at an appointed date
      at a polyclinic. Participants were reminded the day before their appointment by
      telephone, and a new appointment could be given at the subject's convenience.
      RESULTS: We found a prevalence rate of falls of 17.2%. Two-thirds of these had
      single falls, while one-third had recurrent falls, defined as having more than
      one fall within the previous one year. The following factors were found to be
      significantly associated with increase falling in the elderly: age > or = 75
      years (O.R. = 1.82, 95% C.I. 0.95-3.50), female sex (O.R. = 2.5, 95% C.I. 1.40
      4.48), Malay race (O.R. = 2.66, 95% C.I. 1.21-5.86), poor vision (O.R. = 1.7, 95%
      C.I. 0.99-2.90), Barthel's score of less than 20 (O.R. = 1.76, 95% C.I. 0.94
      3.28), those taking 2 or more drugs daily (O.R. = 2.1, 95% C.I. 1.22-3.72) and
      the presence of hypertension (O.R. = 1.78, 95% C.I. 1.06-3.01). Fall rate is also
      twice as high in women as in men. At the same time, we found that women in the
      group we studied also tend to exercise less than the men. Fallers also had
      significantly more mobility and activities of daily living (ADL) disabilities
      (reflected by a lower Barthel's score) and this is consistent with other results.
      The only factor that reduced the risk of falling was regular exercise (O.R. =
      1.64, 95% C.I. 0.93-2.93). CONCLUSION: In our study, we found differences between
      the group with single and recurrent falls. In the group with single falls, the
      fall tend to occur outdoors (O.R. = 2.97, 95% C.I. 1.03-8.60) and during the day
      (O.R. = 3.47, 95% C.I. 1.20-10.0), tend to be accidental (O.R. = 3.16, 95% C.I.
      1.05-9.50) and tend to seek medical attention (O.R. = 3.68, 95% C.I. 1.23-11.0).
      Overall, 32 persons (46.4%) seek medical treatment after their falls, and of
      these, 65.6% were women. Risk factors for falls should be screened for all
      elderly.

PMID- 9529955
TI  - Hypoglycaemia in the elderly.
AB  - AIM: To determine the prevalence, presentation, causes and consequences of
      hypoglycaemia in the elderly, and to make preventive recommendations. METHOD:
      Retrospective review of case records. RESULTS: The definition of hypoglycaemia is
      defined as symptoms with a capillary blood sugar of less than 3 mmol/L measured
      on the Reflolux II or Accutrend glucometer. Out of 1,919 admissions to our
      department from November 1993 to January 1996, there were 45 cases of
      hypoglycaemia. The average age was 76.2 years (range 66 to 89 years); 32 were
      females, 13 males, 35 had diabetes mellitus and 10 were non-diabetics. Forty
      patients presented with neuroglycopaenic symptoms and 5 patients presented with
      adrenergic symptoms. Thirteen patients presented were solely due to drugs (mainly
      glibenclamide); 9 cases were due only to disease (mainly psychiatric illnesses
      with poor intake); 23 cases were due to both drugs and diseases (mainly a
      combination of glibenclamide, tolbutamide and psychiatric illness with poor
      intake, renal failure, gastroenteritis and sepsis). All were easily reversed with
      an intravenous bolus of 50% glucose or continuous 10% glucose infusions. Forty
      three patients did not suffer any morbidity, one suffered a stroke and another
      fell because of giddiness. CONCLUSION: We recommend that: (1) the importance of
      having regular meals be emphasised to elderly patients and their carers,
      especially if they are taking hypoglycaemic agents; (2) regular home glucose
      monitoring for diabetic patients; (3) assessment and monitoring of renal function
      before prescribing hypoglycaemic agents; (4) avoidance of the use of long or
      medium acting sulphonylureas eg. chlorpropamide, glibenclamide in the elderly;
      (5) adjustment of hypoglycaemic agents (in consultation with a trained
      nurse/doctor) if the patient suffers from gastroenteritis and (6) less stringent
      blood glucose control in those with psychiatric illnesses who may have variable
      food intake.

PMID- 9529956
TI  - Spine surgery in geriatric patients.
AB  - AIM: Many elderly patients are crippled by degenerative spine conditions.
      Operative treatment is often not offered due to fear of complications and
      consideration of life span. The objective of this study was to look at the
      diagnosis, surgical results and post-operative complications of elderly patients
      who underwent spinal surgery. METHODS: A cohort of 44 patients, 65 years and
      older, who had surgery in Tan Tock Seng Hospital from January 1990-August 1995
      were reviewed. Twenty-five of them had spinal stenosis, II had tumour and 9 had
      traumatic fracture/dislocation/subluxation. There were 3 patients each with disc
      herniation, infection and spondylolisthesis. Nine patients had more than one
      diagnosis. All patients were investigated post-operatively. The data was entered
      into a computer-coded protocol. The diagnosis was determined intraoperatively.
      Type of surgery, co-morbid conditions and results were looked into. Patient's
      opinion on relief symptoms was graded on a 5-point scale. Functional improvement
      was tabulated as the patient's ambulatory status. RESULTS: The analysis of
      results was divided into two groups, patients with tumour and those without
      tumour. Twenty-seven of the 33 patients without tumour were alive at follow-up.
      Twenty-six of these patients had improvement of symptoms and 18 of 27 had
      improved functional status post-operatively. In the group with tumours, 2 had
      worsening symptoms and 3 had decreased function. CONCLUSION: Surgical
      intervention should be a treatment option in elderly patients with spinal
      disease.

PMID- 9529957
TI  - Depression of young and elderly patients.
AB  - OBJECTIVE: To compare the presentation and outcome of depression between young
      and elderly patients. DESIGN: The clinical presentation, treatment and outcome of
      47 young patients (21 to 64 years) were compared with 58 elderly (65 years and
      older) patients admitted to a general hospital psychiatric ward for the treatment
      of depressive disorders (based on ICD-10). SUBJECTS: There was no significant
      difference between the sexes in each age group. The majority of the elderly were
      either widowed (36%) or married (53%) while 45% of the young were single and 51%
      married. Seventy per cent of the elderly had retired while 64% of the young were
      in full-time employment. Most patients lived with their families (87% young and
      96% elderly). All but one elderly suffered at least one physical disorder with
      two-thirds having two or more physical disorders; this contrasts greatly to young
      patients who were physically healthier (p < 0.001). RESULTS: In clinical
      presentation and symptomatology, the young patients had significantly more
      suicide ideation (p < 0.003) and psychomotor retardation (p < 0.001) but there
      was no difference in suicidal attempt, delusion, hallucination or agitation. More
      young patients (36%) had a past psychiatric illness (often depressive disorders)
      than elderly patients (8%) (p < 0.001), more elderly patients (88%) were treated
      with antidepressants than the young patients (62%) (p < 0.002). At one year
      follow-up, more elderly patients (46%) recovered compared with the young patients
      (23%) (p < 0.05). CONCLUSION: There were some differences in the symptomatology
      of depression between young and elderly patients, but the prognosis was better
      for elderly patients.

PMID- 9529958
TI  - Perforated leiomyosarcoma of Meckel's diverticulum.
AB  - Two cases of perforated leiomyosarcoma of Meckel's diverticulum are presented.
      There are only 59 cases reported in current literature, including 4 perforations.
      Although the condition is rare, leiomyosarcoma is the commonest tumour of
      Meckel's diverticulum. Its clinical presentation include abdominal pain,
      intestinal bleeding, abdominal mass, intestinal obstruction and less commonly,
      acute perforations. Both our cases presented with perforations which is unusual.
      Despite this late presentations both were resectable and both had no distant or
      local metastasis. One of our patients was 89 years old at presentation and has
      been disease-free 3 years after resection. The other patient was 69 years old and
      has also been disease-free.

PMID- 9529959
TI  - Germinoma of the basal ganglia and thalamus--CT and MRI findings.
AB  - A case of germinoma originating in the basal ganglia and thalamus is presented.
      This tumour most commonly originates during childhood and adolescence, at pineal
      and suprasellar regions. In the early stages, the diagnosis of germinoma in the
      basal ganglion and thalamus is difficult because of its rarity and non-specific
      findings. The computed tomography (CT) and magnetic resonance imaging (MRI)
      findings though non-diagnostic, are discussed here. A few differential diagnoses
      had been discussed with radiological abnormality. Open biopsy done in this case
      proved to be two-cell pattern germinoma. Early detection of the tumour is
      desirable, since this tumour is highly sensitive to radio and chemotherapy and is
      potentially curable. Our patient was treated with combined chemotherapy and the
      response was well and no residual tumour or recurrence was seen on the repeated
      imaging modality, however his neurological deficits remained unchanged.

PMID- 9529960
TI  - A case of bilateral ulnar nerve palsy in a patient with traumatic brain injury
      and heterotopic ossification.
AB  - Heterotopic ossification after head injury may occur in the elbow joint. Rarely
      does this lead to entrapment of the ulnar nerve. We describe the case of a 20
      year-old patient who developed heterotopic ossification 6 weeks after a traumatic
      brain injury. She subsequently developed bilateral ulnar nerve palsy which was
      confirmed by electrodiagnostic studies and treated by transposition of the ulnar
      nerve.

PMID- 9529961
TI  - Clinics in diagnostic imaging (30). Vein of Galen and straight sinus thrombosis.
AB  - A 40-year-old lady presented with acute onset of confusion and disorientation. CT
      and MRI scans showed vein of Galen and straight sinus thrombosis. The clinical
      and imaging features of venous sinus thrombosis are described.

PMID- 9529962
TI  - P waves in ECG--variations on a theme.

PMID- 9529963
TI  - What you need to know: tonsillitis--medical and surgical therapy.

PMID- 9529964
TI  - Guidelines on prescription of sedatives.

PMID- 9529965
TI  - Allergy and immunology pioneers.

PMID- 9529966
TI  - County medical societies connect with members online.

PMID- 9529967
TI  - You're still in control. An interview with medical ethicist Laurence B.
      McCullough, PhD.

PMID- 9529968
TI  - Measuring mortality. Texas Medical Association Committee on Maternal and
      Perinatal Health.

PMID- 9529969
TI  - The community continuity experience: generalist training for preclinical medical
      students.
AB  - Many medical schools are planning community-based experiences for preclinical
      students. In August 1994, The University of Texas Medical Branch at Galveston
      began placing all 200 first-year medical students in generalists' offices in a
      new course called the Community Continuity Experience. The office nurse served as
      site facilitator. Activities during the second term provided more opportunities
      for students to interview patients as well as to observe the site physicians. The
      course committee used feedback from student evaluations and focus groups to
      change the implementation of the curriculum. We found that nurses as site
      facilitators effectively managed the students' activities, that continuity of
      site was more important to students than breadth of exposure, that the optimum
      focus of activities was the examination room, that training in actual skill
      development (e.g., methods of patient education) was desired before site
      activities, and that careful integration of preclinical patient-oriented courses
      was important to expose students to a coherent approach to learning skills for
      patient assessment.

PMID- 9529970
TI  - Psychological and legal aspects of mental incompetence.
AB  - The elderly population in the United States is increasing gradually. Estimates
      project that during the next 50 years 21% of the population, or approximately 70
      million people, will be older than 65 years. Various medical and psychiatric
      disorders produce cognitive disturbances that result in temporary or permanent
      incompetence. That incompetence will affect an individual's decision-making
      capacity and ability to give informed consent. Problems exist related to
      obtaining informed consent from the elderly and distinguishing between
      incapacitated versus incompetent individuals. Physicians are responsible for
      providing information to their patients about a durable power of attorney for
      health care, a living will, and "do not resuscitate" orders, before they lose
      their capacity to make decisions related to their health care. Informed consent,
      living wills, durable power of attorney for health care, and guardianship are
      discussed.

PMID- 9529971
TI  - Clinical aspects of leptin.
AB  - Hyperleptinemia is an essential feature of human obesity. Total body fat mass > %
      body fat > BMI are the best predictors of circulating leptin levels. Although ob
      gene is differentially expressed in different fat compartments, apart from total
      body fat, upper or lower body adiposity or visceral fat does not influence basal
      leptin levels. Similarly, age, basal glucose levels, and ethnicity do not
      influence circulating leptin levels. Only in insulin-sensitive individuals do
      basal levels of insulin and leptin correlate positively even after factoring in
      body fat. Diabetes does not influence leptin secretion in both lean and obese
      subjects per se. Independent of adiposity, leptin levels are higher in women than
      in men. This sexual dimorphism is also present in adolescent children. In eating
      disorders anorexia nervosa and bulimea nervosa, leptin levels are not upregulated
      but simply reflect BMI and probably body fat. In spite of strong correlation
      between body fat and leptin levels, there is great heterogeneity in leptin levels
      at any given index of body fat. About 5% of obese populations can be regarded as
      "relatively" leptin deficient which could benefit from leptin therapy. Leptin has
      dual regulation in human physiology. During the periods of weight maintenance,
      when energy intake and energy output are equal, leptin levels reflect total
      bodyfat mass. However, in conditions of negative (weight-loss programs) and
      positive (weight-gain programs) energy balances, the changes in leptin levels
      function as a sensor of energy imbalance. This latter phenomenon is best
      illustrated by short-term fasting and overfeeding experiments. Within 24 h of
      fasting leptin levels decline to approximately 30% of initial basal values.
      Massive overfeeding over a 12-h period increases leptin levels by approximately
      50% of initial basal values. Meal ingestion does not acutely regulate serum
      leptin levels. A few studies have shown a modest increase in leptin secretion at
      supraphysiological insulin concentrations 4-6 h following insulin infusion. Under
      in vitro conditions, insulin stimulates leptin production only after four days in
      primary cultures of human adipocytes, which is apparently due to its trophic
      effects and an increased fat-cell size. Similar to other hormones, leptin
      secretion shows circadian rhythm and oscillatory pattern. The nocturnal rise of
      leptin secretion is entrained to mealtime probably due to cumulative
      hyperinsulinemia of the entire day. Like other growth factors and cytokines,
      leptin binding proteins including soluble leptin receptor are present in human
      serum. In lean subjects, the majority of leptin circulates in the bound form
      whereas in obese subjects, the majority of leptin is present in the free form.
      When free-leptin levels are compared between lean and obese subjects, even more
      pronounced hyperleptinemia in obesity is observed than that reported by measuring
      total leptin levels. During short-term fasting, free-leptin levels in lean
      subjects decrease in much greater proportion than those in obese subjects. In
      lean subjects with a relatively small energy store and particularly during food
      deprivation, leptin circulating predominantly in the bound form could be the
      mechanism to restrict its availability to hypothalamic leptin receptors for
      inhibiting leptin's effect on food intake and/or energy metabolism. Unlike marked
      changes in serum leptin, CSF leptin is only modestly increased in obese subjects
      and the CSF leptin/serum leptin ratio decreases logarithmically with increasing
      BMI. If CSF leptin levels are any indication of brain interstitial fluid levels,
      then hypothalami of obese subjects are not exposed to abnormally elevated leptin
      concentrations. In the presence of normal leptin receptor (functional long form,
      i.e., OB-Rb) mRNA expression and in the absence of leptin receptor gene
      mutations, it is logical to assume defective leptin signaling and/or impaired
      affector system(s) are the likely causes of leptin resistance in

PMID- 9529972
TI  - Alcohol, calories, and appetite.

PMID- 9529973
TI  - Neuropeptide Y-induced feeding and its control.

PMID- 9529974
TI  - Regulation of insulin action by protein tyrosine phosphatases.

PMID- 9529975
TI  - Capacitative calcium influx.

PMID- 9529976
TI  - Regulation of peroxisome proliferator-activated receptors.

PMID- 9529978
TI  - Mechanisms of protein secretion in endocrine and exocrine cells.

PMID- 9529977
TI  - Steroid hormone receptors and heat shock proteins.

PMID- 9529979
TI  - Hyperoxia influences mRNA expression of cytokines in cultured human umbilical
      vein endothelial cells.
AB  - High concentrations of oxygen, indispensable for the treatment of severe
      hypoxemia from neonatal as well as adult respiratory distress syndrome, increase
      the risk of oxygen toxicity. Biochemical mechanisms are lipid peroxidation,
      protein sulfhydryl oxidation, enzyme inactivation, and DNA damage. Recent reports
      suggest that cytokines might be involved in free radical injury as well as in
      adaptive response to hyperoxic injury. However, actual signal transduction
      pathways involving cytokines have not yet been clarified. In this study we
      exposed cultured human umbilical vein endothelial cells (HUVECs) to either
      ambient air or 100% oxygen, and compared for the rate of DNA synthesis
      ([3H]thymidine uptake) at different time points up to 72 h. After exposing the
      cells to each treatment condition, we extracted RNA, constructed complementary
      DNA using reverse transcriptase, amplified the specific DNA segments of cytokines
      by polymerase chain reaction (PCR), and used the PCR products for gel
      electrophoresis to examine the bands which signified mRNA levels of corresponding
      cytokines. There was a significant decrease in the rate of DNA synthesis as early
      as 24 h. The mRNA expression of IL-1 beta and TNFa seemed less influenced by
      hyperoxia, while IL-8 and TGF beta showed marked increase in mRNA levels at 6 h
      of 100% oxygen exposure.

PMID- 9529980
TI  - Immunoreactivity of androgen receptor protein in sexually dimorphic spinal
      motonucleus in neonatal male rats.
AB  - The spinal motonucleus of the genitofemoral nerve regulating scrotal temperature
      can also be related to prenatal and neonatal testicular descent by gubernacular
      change in rats, and a sexually dimorphic-like bulbocavernosus/dorsolateral
      motonucleus. There is a hypothesis that neonatal androgen affects these
      motonuclei, and induces development of sexual organs through neural stimulation.
      Until now, the accumulation of isotope-labelled androgen and the immuno
      reactivity of androgen receptor protein in each sexually-dimorphic spinal
      motonucleus have been revealed in adult rats but they have not been established
      in rats during neonatal periods. To investigate the presence of the androgen
      receptor in spinal sexually-dimorphic motonuclei in the neonatal period, we
      evaluated the androgen receptor immunoreactivity of these motonuclei. In Sprague
      Dawley male rats, the lumbar spinal cords were resected at postnatal days 3, 10
      and 30, and stained immunohistochemically using polyclonal antibody of androgen
      receptor protein. The immunoreactivity of androgen receptor protein was observed
      in the cells of the genitofemoral motonucleus from the 13th thoracic to the 2nd
      lumbar spinal cord and the bulbocavernosus/dorsolateral motonucleus was observed
      from the 4th to 5th lumbar spinal cord in all age groups. The proportional areas
      of both motonuclei at days 3 and 10 on cross-section were larger than at day 30.
      The motonuclei at days 3 and 10 were similar in all age groups. With the above
      results, the presence of androgen receptor protein was confirmed in the
      genitofemoral and bulbocavernosus/dorsolateral motonucleus from neonate to day
      30. The larger proportional area of these motonuclei in neonates may indicate an
      active role for these motonuclei during the neonatal period. Although the
      immunoreactivity does not directly imply the presence of a functional receptor,
      neonatal androgen could be responsible for the development of sexual organs
      through the spinal motonucleus.

PMID- 9529981
TI  - Sialoglycoproteins and penultimate sugar expression pattern in developing murine
      olfactory and respiratory mucosa.
AB  - Sialic acid residues are constant constituents of the glycoproteins of the
      airways in all species. Sialoglycoproteins are the main acidic glycoprotein and
      their functions are to mediate cell adherence, to control the viscoelasticity of
      mucus and to serve as receptor sites for the binding of exogenous macromolecules.
      The purpose of this study was to investigate the differences in the distribution
      of sialoglycoproteins as a terminal sugar and in the composition of the
      penultimate sugar according to aging in the murine nasal respiratory and
      olfactory mucosa. Nasal cavities of mice (BALB/c) were fixed by intracardiac
      perfusion with 2.0% glutaraldehyde and embedded in Epon 812. First, the serial
      sections were stained with Maackia amurensis agglutinin (MAA) and Sambucus nigra
      agglutinin (SNA). Then, the adjacent sections were stained with DBA and PNA
      before and after neuraminidase digestion in all experimental groups. Apical cell
      surfaces of olfactory mucosa and cilia on a few ciliated cells in the mucosa of
      the septum and nasal floor were labelled with MAA, but cell surfaces of
      respiratory mucosa, Bowman's glands and goblet cells were not labelled with MAA,
      irrespective of aging. Apical cell surfaces of both olfactory and respiratory
      mucosa and Bowman's glands were stained with SNA, however, goblet cells were not
      labelled with SNA. After neuraminidase digestion to remove terminal sialic acid
      residues of sialoglycoproteins, only cell surfaces of respiratory mucosa were
      labelled with PNA, but goblet cells, cell surfaces of olfactory mucosa and
      Bowman's glands were not labelled with PNA. Cell surfaces and Bowman's glands of
      olfactory mucosa were labelled with DBA after neuraminidase digestion, but cell
      surfaces of respiratory mucosa and goblet cells were not labelled with DBA. Our
      results indicate that there were different carbohydrate structures of
      sialoglycoconjugates in olfactory and respiratory mucosa, and it was not
      influenced by aging.

PMID- 9529983
TI  - E-cadherin expression in thymomas.
AB  - For the purpose of investigating the pattern of E-cadherin (E-CD) expression in
      thymomas, 72 cases were immunostained using monoclonal antibody (HECD-1) and
      microwave-enhanced immunohistochemical method on formalin-fixed, paraffin
      embedded tissue sections. The thymomas were classified according to modified
      Muller-Hermelink classification. The spindle-shaped, medullary type tumor
      epithelial cells in medullary (3 cases) and composite type (20 cases) thymomas
      rarely expressed E-CD except in focal areas showing microcystic change observed
      in 8 cases. Meanwhile, the cohesive epithelioid tumor cells in every case of well
      differentiated thymic carcinomas (WDTC) (29 cases) expressed E-CD. The epithelial
      cells in cortical type (13 cases) expressed stronger E-CD compared with those of
      organoid type (7 cases). In cases of WDTC admixed with cortical type, we observed
      increasing expression of E-CD as the tumor epithelium forms cohesive sheets. We
      could not find any loss of E-CD expression in invasive foci of the 11 cases of
      high-staged WDTC examined. Since the results of our study show a strong
      correlation between E-CD expression and epithelioid morphology of the tumor, E-CD
      seems to play a major role as a morpho-regulatory factor rather than as a
      suppressor of invasion in organotypic thymomas.

PMID- 9529982
TI  - Synchronous elevation of soluble intercellular adhesion molecule-1 (ICAM-1) and
      vascular cell adhesion molecule-1 (VCAM-1) correlates with gastric cancer
      progression.
AB  - Soluble forms of ICAM-1 (sICAM-1) and VCAM-1 (sVCAM-1) have been reported from
      the supernatant of cytokine-activated endothelial cells, cancer cells and from
      sera of cancer patients. We measured sICAM-1 and sVCAM-1 from the serum of 20
      healthy volunteers and 142 gastric cancer patients by ELISA assay. Ninety-five
      patients were operable and 47 patients were in-operable at the time of this
      study. Particularly in the 28 operable patients, we sampled both portal and
      peripheral blood simultaneously and measured the levels of the soluble forms of
      cell adhesion molecules (sCAMs). The sCAMs level and sero-positivity rate
      increased with cancer progression in order of the healthy controls, operable
      patients, and inoperable patients. In in-operable cancer, the sICAM-1 level
      increased more with liver metastasis. sICAM-1 and sVCAM-1 did not correlate with
      each other in either portal or peripheral blood. A total of 58.3% of patients
      with liver metastasis and 22.9% of patients without liver metastasis showed
      synchronous expression of both sCAMs (p = 0.03). Synchronous sero-positivity of
      sCAMs and alpha FP was higher with liver metastasis (p = 0.01). The median
      overall survival duration which co-expressed both sCAMs was 9 months. This showed
      a significant difference compared with the sICAMs non-expressing group, where the
      median survival was not reached until 24 months follow-up (p = 0.002). The
      synchronous expression of sCAMs was an independent risk factor in gastric cancer
      patients. We raise the possibility that synchronous sICAM-1 and sVCAM-1 elevation
      may be a useful monitor to determine tumor burden in gastric cancer.

PMID- 9529984
TI  - Comparative study of bentiromide test and endoscopic retrograde pancreatography
      in patients with chronic pancreatitis.
AB  - We performed a bentiromide test in 25 patients with chronic pancreatitis and 7
      normal controls to evaluate pancreatic exocrine function, and compared the test
      results of patients with their endoscopic retrograde pancreatography(ERP)
      findings. The cumulative 6-hour recovery rate of para-aminobenzoic acid(PABA) in
      the urine was significantly lower in patients with chronic pancreatitis(55.8 +/-
      24.2%) than in controls(82.0 +/- 10.0%). Among 25 patients with chronic
      pancreatitis, however, 7 patients showed normal recovery rates of PABA.
      Pancreatograms of the patients represented 4 mild changes, 5 moderate changes,
      and 16 marked changes. The average 6-hour recovery rates of PABA of the groups
      were 56.9 +/- 21.6%, 78.4 +/- 10.5%, and 47.2 +/- 23.7%, respectively. Urinary
      PABA recovery rates were found subnormal as follows: 3(75%) in the mild changes
      group; 1(20%) in the moderate changes group; and 14(87.5%) in the marked changes
      group. We found hardly any correlation between the degree of functional
      impairment and the changes noted by ERP. These findings suggest that both the
      pancreatic function test and morphologic study are required to evaluate the
      degree of functional impairment in patients with chronic pancreatitis.

PMID- 9529985
TI  - The influence of white matter hyperintensities on the clinical features of
      Parkinson's disease.
AB  - This study was designed to investigate the influence of white matter
      hyperintensities (WMH) on clinical features of Parkinson's disease (PD) patients.
      The study subjects were 44 patients with PD who took a brain MRI. The severity of
      Parkinsonian symptoms was assessed in both 'on' and 'off' states, using the UPDRS
      motor score. Thirteen patients (30%) showed WMH. The patients with WMH were
      significantly older than those without WMH (67 +/- 5.7 vs 60 +/- 6.4 years). In
      both 'off' and 'on' states, the gait scores were significantly higher in patients
      with WMH than in those without WMH (1.6 +/- 0.18 vs 1.1 +/- 0.12, P < 0.05), but
      other motor symptom (tremor, bradykinesia, rigidity) scores between the two
      patient groups were not statistically different. After taking a single dose of
      oral levodopa/benserazide (200mg/50mg), the patients with WMH showed
      significantly less improvement in bradykinesia score than those without WMH (25
      +/- 4.1% vs 40 +/- 4.0%, P < 0.05), but the improvements in other symptoms were
      comparable between the two groups. These results suggest that WMH on MRI may
      influence Parkinsonian motor symptoms, particularly gait symptom and levodopa
      responsiveness to bradykinesia symptom.

PMID- 9529987
TI  - Progression of hypertrophic cardiomyopathy to dilated cardiomyopathy--a case
      reports and review of the literatures.
AB  - Left ventricular systolic function in hypertrophic cardiomyopathy (HCMP) does not
      usually deteriorate even in the end stage of the disease. However, occasionally
      cases of HCMP progress to a similar form of dilated cardiomyopathy (DCMP) with a
      decreased systolic function and dilated left ventricle. We report two cases of
      HCMP which progressed to DCMP during follow-up. Our cases have been documented by
      serial M-mode echocardiography which shows a prominent decrease in the left
      ventricular systolic function and a chamber enlargement of the left ventricle.
      There are various explanations of the pathogenesis of the functional and
      morphological myocardial deterioration of HCMP progressing to DCMP, and more
      cases should be studied to determine the pathogenesis and prevention of this end
      stage feature of HCMP.

PMID- 9529986
TI  - Effects of t-butyl hydrogen peroxide on single SR calcium release channels.
AB  - Using lipid bilayer reconstitution technique, we investigated the oxidation
      effect of t-butyl hydrogen peroxide (tBHP) on the single channel activity of the
      sarcoplasmic reticulum (SR) calcium release channels isolated from canine
      latissimus dorsi muscles. When 0.7% tBHP was added in the cytosolic side, the
      channel activity became suppressed (n = 7), and it was recovered by changing the
      solution to the control solution. The suppression was due to the change in the
      gating mode of the channel: before tBHP the channel opened to four sub
      conductance levels, but it opened to only one level after tBHP. These effects by
      tBHP were different from the previous finding using hydrogen peroxide (H2O2),
      which may be explained by different oxidation patterns between the two oxidants.

PMID- 9529988
TI  - Fabry's disease--a case report and review of literatures reported in Korea.
AB  - Fabry's disease is a rare, X-linked disorder of the glycosphingolipid metabolism,
      in which a partial or total deficiency of a lysosomal alpha(alpha)-galactosidase
      results in the progressive accumulation of neutral glycosphingolipids with
      terminal alpha galactose moieties (i.e., cerebroside di- and trihexoside) in most
      body fluids and tissues. Accumulation of neutral glycosphingolipids occurs within
      the lysosomes of endothelial, perithelial, and smooth muscle cells of the
      myocardial and renal systems; to a lesser extent in reticuloendothelial and
      connective cells of the cornea; and in ganglion and perineural cells of the
      autonomic nervous system. In Korea, 7 cases of Fabry's disease have been
      reported. A 29-year-old man with fever and headache had typical skin findings and
      a family history of Fabry's disease, and it was confirmed through renal biopsy
      and enzyme assay for alpha-galactosidase. We report a case of Fabry's disease
      with a review of the literatures reported in Korea.

PMID- 9529989
TI  - Acute scrotum in 7 cases of Schoenlein-Henoch syndrome.
AB  - Schoenlein-Henoch syndrome (SHS), one of the manifestations of systemic
      vasculitis, usually involves the skin, gastrointestinal tract, joints and kidney.
      Since the involvement of male genitalia is very rare and there is little mention
      of it in textbooks, doctors have a tendency to neglect this finding in SHS.
      Unless there is a confirming diagnosis, it is easily mistaken for testicular
      torsion and the patients undergo unnecessary operations because they complain of
      unbearable scrotal pain. SHS is not uncommon in Korea, but hardly any cases of
      scrotal involvement are found. We have experienced 7 cases of acute scrotum
      associated with SHS admitted to Severance Hospital, Yonsei University College of
      Medicine during the last 20 years; 2 underwent operation and 5 received
      conservative treatment only.

PMID- 9529990
TI  - Increase in C-reactive protein in the serum of piglets (pCRP) following ACTH or
      corticosteroid administration.
AB  - A new isolation procedure for porcine C-reactive protein (pCRP) by affinity
      chromatography and ion-exchange chromatography is described. Antisera against
      this protein were raised in rabbits. Immunochemical methods indicate a close
      immunological relationship of pCRP to human CRP (hCRP). The molecular weight of
      one subunit of pCRP was determined to be 23,400 Da by SDS-PAGE. Measurements of
      serum concentration of pCRP by competitive ligand assay and radial
      immunodiffusion showed a good correlation. Normal values of healthy pigs, kept
      under good conditions, were 8.35 mg/l with a normal range up to 16.8 mg/l (3 x
      SD). ACTH or prednisolone were applicated to piglets daily for a period of 2
      weeks and the pCRP concentration in serum was measured. There was a strong pCRP
      elevation during the application period in comparison to a control group. When
      the stimulus disappeared, the values declined to normal. In the absence of
      infections and inflammations, the pCRP appears to be a valuable parameter for
      following the effects of stress on animals.

PMID- 9529991
TI  - Signs of infections and reduced immune functions at weaning of conventionally
      reared and specific pathogen free pigs.
AB  - The growth rate and several immune parameters were recorded to monitor the
      performance, health and immune status of 40 piglets in a conventional farrow to
      finish herd. In addition, effects of weaning on immune parameters were studied
      under minimal influence of infections in 20 specific pathogen free (SPF) pigs.
      The growth rate of the conventionally reared pigs decreased after weaning and
      after allocation of pigs to new premises. Around weaning a considerable number of
      pigs displayed interferon-alpha (IFN-alpha) in serum, indicating the spread of
      viral infections. Bacterial infections were indicated by elevated numbers of
      circulating neutrophilic granulocytes during the weaning period. Functional in
      vitro tests of peripheral blood mononuclear cells (PBMC) revealed that the
      Concanavalin A (Con A) induced proliferation decreased both after weaning and
      after transfer of the conventionally reared pigs to the finishing unit. The
      decreased proliferation observed after weaning was accompanied by decreased
      interleukin-2 (IL-2) production in response to the mitogen. A reduced IL-2
      producing capacity after weaning was confirmed with PBMC obtained from the SPF
      pigs. Flow cytometric analyses of these cells showed that the proportion of PBMC
      expressing IL-2 receptors (IL-2R+) was decreased 3 and 6 days after weaning when
      cultured in the absence of mitogen while the proportion of IL-2R+ cells was
      unaltered in Con A stimulated cultures. Thus indications of reduced immune
      function coincided in time with signs of infections, especially around weaning.

PMID- 9529992
TI  - Development of an experimental tissue culture vaccine against Mediterranean
      theileriosis in Spain.
AB  - Vaccines against Mediterranean theileriosis have been developed in several
      countries where the disease is an economic problem. Tissue culture vaccines have
      been widely and successfully used to immunize cattle. Although Mediterranean
      theileriosis represents a constraint to dairy cattle production in Spain, no
      vaccines against this disease have been developed previously. The successful
      development of a tissue culture vaccine consisting of attenuated Theileria
      annulata schizont infected cells from an enzootic area of Spain and its efficacy
      under experimental conditions is reported. Vaccinated calves were resistant to
      homologous challenge showing no signs of theileriosis while non-vaccinated calves
      showed typical signs of disease.

PMID- 9529994
TI  - Corynebacterium pseudotuberculosis infection in goats in the Czech Republic.
AB  - Prevalence of caseous lymphadenitis was studied in goats from six herds in the
      Czech Republic. Corynebacterium pseudotuberculosis exhibiting typical properties
      was isolated from clinically affected animals only. Antibodies to C.
      pseudotuberculosis were identified by means of agar immunodiffusion and the
      neutralization test using a toxin--phospholipase D (PLD)--as antigen. No clinical
      manifestations of caseous lymphadenitis or antibodies to C. pseudotuberculosis
      were found in four herds. In one herd without any history of clinical caseous
      lymphadenitis, serological positivity was reported in two out of 148
      examinations. In a herd with clinical manifestations of caseous lymphadenitis,
      antibodies were ascertained to a various degree in subsequent samplings (100%,
      87% and 64%, respectively). The importance of serologic examination of caseous
      lymphadenitis in goat herds is discussed.

PMID- 9529993
TI  - Selective loss of BoLA class I determinants from the lymphocyte surface after
      acid treatment.
AB  - Acid treatment of bovine lymphocytes by a buffered solution of 0.263 m citric
      acid and 0.123 M Na2HPO4 at pH = 3.0, originally described for human and murine
      lymphocytes, selectively eliminated the antigenicity of MHC (BoLA) class I
      determinants also from bovine lymphocytes. The viability of acid-treated cell
      suspension was higher than 90%. The reactivity of acid-treated lymphocytes with
      BoLA class I typing alloantisera was lost in microcytotoxicity test, while their
      reactions with cross-reactive anti-HLA class II, anti-BoCD2 and BoCD5 monoclonal
      antibodies, and with antisera detecting two non-MHC lymphocyte alloantigenic
      specificities (BoLY w1 and R') remained unchanged in the microcytotoxicity and/or
      indirect immunofluorescence tests. The results thus show that this approach of
      modulating cell surface expression of MHC class I determinants may be used in
      cattle.

PMID- 9529996
TI  - Histopathological and ultrastructural observations of ovine mammary glands
      experimentally inoculated with coagulase-negative staphylococci.
AB  - The mammary glands of 21 primiparous Mule ewes were infected experimentally with
      one or other of seven isolates of coagulase-negative staphylococci belonging to
      one of four different species. All isolates caused inflammation that contributed
      to histopathological and ultrastructural changes. Histopathological changes
      varied from various degrees of neutrophilic inflammation at the early stages of
      infection to extensive mononuclear cell infiltration and development of fibrotic
      tissue at the late stages. The severity and extent of the lesions varied between
      isolates. At late stages of infection mononuclear cells were involved in active
      phagocytosis more often than neutrophils. Phagocytosed cocci within mononuclear
      cells were observed in the interstitium. These cells could become reservoirs of
      staphylococci that may prolong the inflammatory response.

PMID- 9529995
TI  - Water as a reservoir for Campylobacter jejuni infection in cows studied by
      serotyping and pulsed-field gel electrophoresis (PFGE).
AB  - The occurrence of campylobacters was studied in the faecal samples of a dairy
      herd with about 20 animals and in the lake which was their source of drinking
      water during the grazing period from June to September. Of the total of 141
      faecal samples studied, 0-21% were found to be positive for C. jejuni at various
      sampling times throughout the year. More cows were found to be campylobacter
      positive in summer or in autumn after the grazing period than after the winter,
      when the animals were inside and their drinking water source was municipal
      chlorinated tap water. C. jejuni was isolated from most of the lake water
      samples. Serotyping with heat stable antigens and molecular typing with PFGE
      using SacII- and SmaI-digested DNA revealed that an animal that was permanently
      infected with C. jejuni sero-/PFGE-type PEN 0:6, 25/I/ND most probably
      contaminated the lake water in summer 1987. This was the only sero/PFGE-type
      isolated from the lake water in summer and autumn 1987 and in spring 1988. This
      sero/PFGE-type was also isolated from four other cows in autumn 1987, suggesting
      that lake water was the source of the infection. This study is first to employ
      molecular methods to assess the possible role of contaminated drinking water in
      the transmission of campylobacter infection within a dairy herd.

PMID- 9529997
TI  - Microbial hazard of salted OM El-Kholoul (wedge shell Donax trunculus).
AB  - Sixty samples of salted OM El-Kholoul were collected from different localities in
      Giza, Alexandria and Ismailia. The samples were examined organoleptically and
      bacteriological examination of samples were performed for enumeration of aerobic,
      Enterobacteriaceae, Staph. aureus, Enterococci counts as well as isolation and
      identification of Vibrio parahaemolyticus. The mean counts/gm of aerobes,
      Enterobacteriaceae, Staph. aureus, Strept. faecalis and Strept. faecum were 4.9 x
      10(5), 4.8 x 10(4), 1.9 x 10(5), 1.5 x 10(5) and 8 x 10(2), respectively. V.
      parahaemolyticus was isolated from all examined samples. Moreover, the weight, pH
      and sodium chloride percentage of ten samples were estimated. Trial was done to
      investigate the inhibitory effect of lemon juice (Citrus aurantifolia) on the
      microbial load of Om El-Kholoul, where the inhibitory effect of this juice was
      noticed. The public health significance of isolated microorganisms was discussed,
      moreover the suggestive measures for improvement of the microbial quality of the
      product were mentioned.

PMID- 9529998
TI  - Studies of Yersinia enterocolitica 0:3 experimental infection in pigs.
AB  - Y. enterocolitica (serotype 0:3, pYV+, biotype 4) infection of 20-day-old pigs
      challenged per os with a total dose of 5 x 10(10) CFU was studied. Clinical,
      paraclinical and morphological findings were examined in dynamics from 1st to
      25th days post infection (p.i.). Augmentation of body temperature and erythrocyte
      sedimentation rate during the first days p.i. were established. The number of
      leucocytes, peritoneal (pMa) and alveolar (aMa) macrophages was increased
      significantly from 4th to 15th days p.i. Phagocytic activity of pMa and aMa
      examined in vitro was maximal on days 15 and 25 p.i. The enhanced phagocytic
      activity of macrophages was in correlation with the observed histological changes
      -purulent meningoencephalitis, necrotic tonsillitis, peribronchial lymphoid
      leucocytic cell infiltration and catarrhal enteritis. Extensive colonization of
      internal organs was detected at necropsy till the end of trial. Analysis of the
      results shows that this orally caused infection runs slowly with dissemination
      and persistency of Y. enterocolitica 0:3 in the macroorganism, like a generalized
      infection.

PMID- 9529999
TI  - Characterization and evaluation of d-(+)-tubocurarine chloride as a chiral
      selector for capillary electrophoretic enantioseparations.
AB  - A new macrocyclic of the bis(benzylisoquinoline) alkaloid family, d-(+)
      tubocurarine chloride (DTC), has been evaluated as a chiral selector for the
      separation of optical isomers of organic carboxylates using capillary
      electrophoresis (CE). The pertinent physicochemical properties, such as
      absorption spectrum, isoionic point, and solution conformation, of DTC were
      determined. The effects of varying such experimental parameters as DTC
      concentration, pH, and methanol content in the running buffer were assessed. CE
      separation of the enantiomers of 18 different compounds was achieved using DTC as
      the chiral selector under optimized background electrolytic conditions.

PMID- 9530000
TI  - Separation of chemical warfare agent degradation products by the reversal of
      electroosmotic flow in capillary electrophoresis.
AB  - We report the development of analyses for nerve agent degradation products or
      related species by the reversal of electroosmotic flow in capillary
      electrophoresis (CE). The developed methods were used in this laboratory for
      analysis of samples in the second and third official proficiency tests
      (International Round-Robins) for the Provisional Technical
      Secretariat/Preparatory Commission for the Organization for the Prohibition of
      Chemical Weapons, and those results are reported here. Analytes studied include
      methylphosphonic acid (a dibasic acid), the monoisopropyl ester of
      ethylphosphonic acid, and the monoalkyl esters of methylphosphonic acid (R =
      ethyl, isopropyl, isobutyl, pinacolyl (3,3-dimethyl-2-butyl), cyclohexyl, and 2
      ethylhexyl). The cationic surfactants used here for the reversal of
      electroosmotic flow are didodecyldimethylammonium hydroxide and
      cetyltrimethylammonium hydroxide. CE methods using conductivity or indirect UV
      detection provide a good separation efficiency and very high sensitivity for the
      analysis of such compounds. The detection limits for these species were about 75
      micrograms/L when using conductivity detection and about 100 micrograms/L when
      using indirect UV detection. Because pH plays an important role in the CE
      separation of the alkylphosphonic acids and their monoesters, the influence of pH
      on these separation systems was investigated. Electrolytes were stable for at
      least 3 months. Excellent separation efficiency and freedom from interference due
      to common anions were obtained in the developed methods which typically achieved
      complete separations in less than 3 min. The method was applied to aqueous
      leachates of soil, wipes of surfaces, and vegetation sampled from a field site
      known to have been exposed to nerve agents and subsequently cleaned up. The data
      from these environmental samples indicated that the method can be expected to be
      useful for environmental monitoring.

PMID- 9530002
TI  - Diffraction-based cell detection using a microcontact printed antibody grating.
AB  - An optical detector has been fabricated that is specific for targeted bacterial
      cells, by stamping an antibody grating pattern on a silicon surface. The antibody
      grating alone produces insignificant optical diffraction, but upon immunocapture
      of cells, the optical phase change produces a diffraction pattern. This technique
      eliminates much of the surface modifications and the secondary immunochemical or
      enzyme-linked steps that are common in immunoassays. Microcontact printing
      provides an alternative to previously reported photolithographic-mediated
      antibody patterning processes and uses a photolithographic process simply to
      produce the elastomeric stamp. We have stamped antibodies directly onto clean
      native oxide silicon substrates with no other chemical surface treatments. Direct
      binding of the antibodies to the silicon occurs in a way that still allows them
      to function and selectively bind antigen. The performance of the sensor was
      evaluated by capturing Escherichia coli O157:H7 cells on the antibody-stamped
      lines and measuring the intensity of the first-order diffraction beam resulting
      from the attachment of cells. The diffraction intensity increases in proportion
      to the cell density bound on the surface.

PMID- 9530001
TI  - Development of a highly sensitive enzyme-linked immunosorbent assay based on
      polyclonal antibodies for the detection of polychlorinated dibenzo-p-dioxins.
AB  - The development of an enzyme-linked immunosorbent assay (ELISA) based on
      polyclonal antibodies for the polychlorinated dibenzo-p-dioxins is described. We
      previously reported the synthesis of haptens and generation of antibodies for
      detection of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Antisera were screened
      with seven different coating antigens (hapten-protein conjugates), including
      trans-3-(7,8-dichlorodibenzo-p-dioxin-2-yl)-cis-2-methylpropeno ic acid (VII) and
      5-(3,7,8-trichlorodibenzo-p-dioxin-2-yl)penta-trans,trans-2,4-dien oic acid (X).
      All inhibition screening and optimization studies were conducted using a less
      toxic surrogate standard for TCDD [2,3,7-trichloro-8-methyl-dibenzo-p-dioxin
      (TMDD; XVII)] which responded similarly to 2,3,7,8-TCDD in the ELISA. The most
      sensitive assay from the screening studies [coating antigen VII-BSA, 0.1
      microgram/mL, and antiserum 7598 (anti-X-LPH), 1:10,000] was further optimized
      and characterized. It exhibited an IC50 value of 12 pg/well (240 pg/mL), with
      working range from 2 to 240 pg/well (40 to 4800 pg/mL). The influence of various
      physical and chemical factors (time, solvent, detergent) was investigated. The
      optimized assay was then used to assess cross-reactivity by congeners of
      halogenated dioxins and related structures. DMSO up to concentrations of 37.5%
      decreased the IC50 value in the assay, whereas methanol to concentrations of 30%
      did not lead to improved IC50 values.

PMID- 9530003
TI  - On-line electrochemical sensor for selective continuous measurement of
      acetylcholine in cultured brain tissue.
AB  - An on-line acetylcholine (ACh) sensor was developed in order to determine
      extracellular ACh concentrations without interference from choline (Ch). The
      sensor is composed of a small-volume enzymatic prereactor (22-microL inner
      volume) in which choline oxidase and catalase are immobilized in series. Carbon
      electrodes were modified with an acetylcholine esterase (AChE), choline oxidase
      (ChOx), and osmium poly(vinylpyridine)-based redox polymer containing horseradish
      peroxidase (Os-gel-HRP). The sensor sensitivity was 43.7 nA/microM (+/- 0.15, n =
      3) for ACh under optimized conditions. Almost no response was seen when 100
      microM Ch was continuously injected. The detection limit for ACh with the sensor
      was comparable to that obtained using liquid chromatography with electrochemical
      detection combined with an enzymatic reactor. The electrical stimulation of
      cultured rat hippocampal tissue resulted in an extracellular ACh increase of 20
      nM (+/- 11 nM, n = 3). This increase was observed continuously with our online
      sensor combined with a microcapillary sampling probe located very close to the
      tissue. The continuous measurement of ACh and Ch using a split disk carbon film
      dual electrode in which one electrode surface was modified with ChOx/Os-gel-HRP
      and the other with AChE-ChOx/Os-gel-HRP bilayer film was also demonstrated to
      improve the response time by eliminating the prereactor.

PMID- 9530004
TI  - A laser ablation method for the spatial segregation of enzyme and redox sites on
      carbon fiber microelectrodes.
AB  - A laser-generated interference pattern was used to remove enzyme from micrometer
      wide stripes on an enzyme-covered carbon fiber microelectrode surface to create
      regions of facile electron transfer. Fluorescence microscopy was used to
      visualize fluorophore-tagged enzyme to indicate where the adsorbed enzyme
      remained on the surface. The electrochemical kinetics of the carbon fiber surface
      were examined to see if electron-transfer sites could indeed be segregated from
      enzyme adsorbed across the entire surface. CCD imaging of the electrochemical
      luminescence of Ru(bpy)3(2+) was used to verify the segregation between
      photoablated sites (with facile electron-transfer kinetics) and surfaces with
      adsorbed enzyme (which exhibit slow electron-transfer kinetics). The laser
      ablated surface could also be distinguished from the enzyme-covered carbon
      surface with atomic force microscopy. Thus, photoablation of the surface of a
      protein-covered carbon fiber microelectrode with an interference pattern
      generated by a Nd:YAG laser allows the activation of 1.7-micron-wide bands of the
      electrode surface (available for facile electron transfer) while leaving 2.6
      micron-wide enzyme-modified areas intact, thereby producing electroactive regions
      directly adjacent to enzyme modified regions of the same surface.

PMID- 9530005
TI  - Regenerable biosensor platform: a total internal reflection fluorescence cell
      with electrochemical control.
AB  - A new biosensor platform that provides simultaneous fluorescence detection and
      electrochemical control of biospecific binding has been developed and
      investigated using antibody-antigen and streptavidin-biotin interactions.
      Specifically, biotin was covalently bound to a transparent indium-tin oxide (ITO)
      working electrode, which also served as an integral part of a total internal
      reflection fluorescence (TIRF) flow cell. TIRF was used to monitor biospecific
      interactions, while electrochemical polarization was employed to control
      interactions between biotin and streptavidin or between biotin and anti-biotin
      antibodies. Both streptavidin and polyclonal anti-biotin antibodies bound
      kinetically irreversibly to the biotinylated surface. In the absence of
      electrochemical control, the assay exhibited an extremely slow release of the
      bound analytes, causing poor regeneration ability of the biosensor surface.
      However, electrochemical polarization was found to stimulate dissociation of
      kinetically irreversibly bound biotin-streptavidin and antibody-antigen
      complexes. A "square wave" polarization function stimulated dissociation more
      effectively than a "saw tooth" function over the same voltage range. Application
      of the square wave polarization resulted in regeneration of an active
      biotinylated surface. Electrochemical polarization also modified affinity and
      kinetics of protein adsorption, which could likely be used to promote biospecific
      interactions and/or to suppress nonspecific adsorption.

PMID- 9530006
TI  - Single-cell measurements of purine release using a micromachined
      electroanalytical sensor.
AB  - To study the cellular events surrounding the formation of purines in cardiac
      ischemia, we have micromachined a micrometer-scale titer chamber containing an
      integrated electrochemical sensor, capable of measuring analytes produced by a
      single heart cell. The analytical procedure involves the determination of
      metabolites via the amperometric detection of enzymically generated hydrogen
      peroxide, measured at a platinized microelectrode, poised at a suitably oxidizing
      potential, equivalent to +420 mV vs Ag/AgCl. Signals were recorded as current
      time responses and were integrated to give a total charge (Q) attributable to the
      reaction under investigation. The amount of analyte produced by the cell was
      subsequently quantified by the addition of a known amount of calibrant. As a
      consequence, by using a cascade of three enzymes (adenosine deaminase, nucleotide
      phosphorylase, and xanthine oxidase), we were able to show that, after rigor
      contracture had been induced in a single myocyte, adenosine (but not inosine)
      only reached the extracellular space after the cell membrane had been
      permeabilized by detergent. These data, which could only be obtained
      unambiguously by using this single-cell methodology, have provided us with
      information on the origin of ischemic adenosine which challenges the established
      assumption that purine release is an early retaliatory response from intact
      anoxic myocytes.

PMID- 9530007
TI  - Sol-gel-derived thick-film amperometric immunosensors.
AB  - Sol-gel processing is used for the first time for the preparation of
      electrochemical immunosensors. One-step sensor fabrication, based on the coupling
      of sol-gel and screen-printing technologies, is employed. A low-temperature cured
      ink is prepared by dispersion of rabbit immunoglobulin G (RIgG), graphite powder,
      and a binder in the sol-gel solution. The enzyme-labeled antibody can readily
      diffuse toward the encapsulated antigen, which retains its binding properties,
      and the association reaction is easily detected at the dispersed graphite
      surface. Use of anti-RIgG labeled with alkaline phosphatase, naphthyl phosphate
      as the substrate, and amperometric detection at +400 mV (vs Ag/AgCl) results in a
      low detection limit of 5 ng/mL (32 pM) for the solution antigen. Tailoring the
      porosity of the ceramic-carbon matrix can be used for tuning the assay
      performance. The high sensitivity, low cost, durability, and simplicity of the
      new single-use immunosensors make them well suited for various on-site
      applications.

PMID- 9530008
TI  - The waveguide Mach-Zender interferometer as atrazine sensor.
AB  - Immunoanalytical techniques used in combination with a highly sensitive Mach
      Zender waveguide sensor give a device that is capable of fast on-line monitoring
      of immunoreactions. The on-line monitoring is especially attractive when the
      sensor can be used as an environmental probe. It is demonstrated that low
      concentrations of atrazine can be measured with a sensitivity around the EC limit
      of 100 ng/L. These measurements are performed with an inhibition technique. In
      combination with "a dynamic slope method" one complete measurement is done within
      10 min. Sensor measurements show the same sensitivity and errors as parallel
      ELISAs.

PMID- 9530009
TI  - Ion/ion proton-transfer kinetics: implications for analysis of ions derived from
      electrospray of protein mixtures.
AB  - Protein ions of different mass and charge but similar mass-to-charge ratios are
      shown to undergo significantly different rates of differential neutralization,
      defined as the rate of change of charge with time, upon initiation of reactions
      with oppositely charged ions in the quadrupole ion trap. Overlapping charge state
      distributions arising from mixtures of ions of dissimilar charge are separated on
      the mass-to-charge scale at short reactions times. It is also demonstrated that
      the time frame for near total neutralization, defined as charge reduction to the
      1+ ion, is relatively insensitive to initial charge state. It is shown, for
      example, that the (M + 11H)(11+)-(M + 22H)22+ ions derived from horse skeletal
      muscle apomyoglobin yield the (M + H)+ ion as the major ion/ion reaction product
      over the same reaction period that largely converts doubly protonated bradykinin
      to the singly protonated species. Less than 25% of the bradykinin ions are
      expected to be totally neutralized when roughly 7% of the myoglobin ions are
      expected to be totally neutralized. The phenomenon of significantly different
      initial differential neutralization rates for ions of dissimilar charge, and the
      relative insensitivity to ion charge for total neutralization, can be used to
      advantage in strategies for protein ion mixture analysis.

PMID- 9530010
TI  - Heterogeneity in Bacillus cereus PCR products detected by ESI-FTICR mass
      spectrometry.
AB  - PCR amplification of a segment of the 16/23S rDNA interspace region (ISR) from
      Bacillus cereus 6464 produced a mixture of products. An 89-bp product was
      predicted on the basis of the reported sequence. The ESI-FTICR analysis revealed
      three double-stranded products, differing in size by a single nucleotide
      corresponding to two homoduplexes of 89 and 88 base pairs and a heteroduplex of
      89 and 88 nucleotide strands. These were produced from a single preparation of
      genomic DNA and a single primer pair. ESI-FTICR analysis of the single strands
      identified a deletion of a T in the coding strand and a corresponding loss of an
      A in the noncoding strand of this product. The ESI-FTICR analysis indicated the
      presence of an unreported sequence variation between rRNA operons in this
      organism. This report illustrates that PCR products amplified from templates
      differing by a single nucleotide can be resolved and identified using ESI-FTICR
      at the 89-bp level. Furthermore, the ESI-FTICR mass measurements provided the
      identity of the deletion, which is indicative of interoperon variability.

PMID- 9530011
TI  - Unknown peptide sequencing using matrix-assisted laser desorption/ionization and
      in-source decay.
AB  - The results of a study to determine the utility of in-source decay fragmentation
      of matrix-assisted laser-desorbed ions for obtaining useful sequence information
      on unknown peptides are presented. Six peptides were purified by high-performance
      liquid chromatography and submitted as single blind unknowns. The in-source decay
      fragment ion data were collected on a linear time-of-flight mass spectrometer
      equipped with delayed extraction. These fragment ion data were manually
      interpreted on the basis of known fragmentation pathways to determine a proposed
      sequence. The proposed sequences for three of the unknowns were essentially
      correct, with a few minor errors. A fourth unknown had significant errors
      associated with its proposed sequence due to misinterpretation of the
      fragmentation data. Two unknowns were found to have undergone significant sample
      degradation prior to analysis, which compromised the results for these samples.
      An example of the use of protein database searching of a partial peptide sequence
      to aid in a sequence determination is also presented.

PMID- 9530012
TI  - Decomposition of acenaphthylene by ultrasonic irradiation.
AB  - Polycyclic aromatic hydrocarbons were extracted from a soil sample using
      ultrasound and dichloromethane-, cyclohexane-, and toluene-water mixtures. It was
      found that when dichloromethane is used as an extractant, acenaphthylene reacts
      with the solvent. Several chlorinated and oxygenated derivatives were identified.
      The results show that chlorinated solvents should be avoided because of their
      sonolytic decomposition. Particularly unsaturated nonaromatic compounds might
      react with intermediate decomposition radicals of the solvent.

PMID- 9530013
TI  - Cold denaturation of a synthetic collagen mimetic.

PMID- 9530014
TI  - Correlation between rate of enzyme-substrate diffusional encounter and average
      Boltzmann factor around active site.
AB  - The utility of the average Boltzmann factor around the active site of an enzyme
      as the predictor of the electrostatic enhancement of the substrate binding rate
      is tested on a set of data on wild-type acetylcholinesterase and 18 charge
      mutants recently obtained by Brownian dynamics simulations. A good correlation
      between the average Boltzmann factors and the substrate binding rate constants is
      found. The effects of single charge mutations on both the Boltzmann factor and
      the substrate binding rate constant are modest, i.e., < 5 fold increase or
      decrease. This is consistent with the experimental results of Shafferman et al.
      but does not support their suggestion that the overall rate of the catalytic
      reaction is not limited by the diffusional encounter of acetylcholinesterase and
      its substrate.

PMID- 9530015
TI  - Local control of peptide conformation: stabilization of cis proline peptide bonds
      by aromatic proline interactions.
AB  - In the native state of proteins there is a marked tendency for an aromatic amino
      acid to precede a cis proline. There are also significant differences between the
      three aromatic amino acids with Tyr exhibiting a noticeably higher propensity
      than Phe or Trp to precede a cis proline residue. In order to study the role that
      local interactions play in these conformation preferences, a set of tetrapeptides
      of the general sequence acetyl-Gly-X-Pro-Gly-carboxamide (GXPG), where X = Tyr,
      Phe, Trp, Ala, or cyclohexyl alanine, were synthesized and studied by nmr.
      Analysis of the nmr data shows that none of the peptides adopt a specific
      backbone structure. Ring current shifts, the equilibrium constant, the Van't Hoff
      enthalpy, and the measured rate of cis-trans isomerization all indicate that the
      cis proline conformer is stabilized by favorable interactions between the
      aromatic ring and the proline residue. Analysis of the side chain conformation of
      the aromatic residue and analysis of the chemical shifts of the pyrrolidine ring
      protons shows that the aromatic side chain adopts a preferred conformation in the
      cis form. The distribution of rotamers and the effect of an aromatic residue on
      the cis-trans equilibrium indicate that the preferred conformation is populated
      to approximately 62% for the Phe containing peptide, 67% for the Tyr containing
      peptide, and between 75 and 80% for the Trp containing peptide. The interaction
      is unaffected by the addition of 8M urea. These local interactions favor an
      aromatic residue immediately preceding a cis proline, but they cannot explain the
      relative propensities for Phe-Pro, Tyr-Pro, and Trp-Pro cis peptide bonds
      observed in the native state of proteins. In the model peptides the percentage of
      the cis proline conformer is 21% GYPG while it is 17% for GFPG. This difference
      is considerably smaller than the almost three to one preponderance observed for
      cis Tyr-Pro peptide bonds vs cis Phe-Pro peptide bonds in the protein database.

PMID- 9530016
TI  - Metrics for cortical map organization and lateralization.
AB  - Cerebral lateralization refers to the poorly understood fact that some functions
      are better controlled by one side of the brain than the other (e.g. handedness,
      language). Of particular concern here are the asymmetries apparent in cortical
      topographic maps that can be demonstrated electrophysiologically in mirror-image
      locations of the cerebral cortex. In spite of great interest in issues
      surrounding cerebral lateralization, methods for measuring the degree of
      organization and asymmetry in cortical maps are currently quite limited. In this
      paper, several measures are developed and used to assess the degree of
      organization, lateralization, and mirror symmetry in topographic map formation.
      These measures correct for large constant displacements as well as curving of
      maps. The behavior of the measures is tested on several topographic maps obtained
      by self-organization of an initially random artificial neural network model of a
      bihemispheric brain, and the results are compared with subjective assessments
      made by humans.

PMID- 9530017
TI  - A note on the tangle model for DNA recombination.
AB  - The tangle model developed by Ernst and Sumners provides a rigorous framework to
      study processive DNA recombination. We suggest here a slight modification of that
      model. The tangle equations become: N(S) = b(1, 1), N(S + M) = b(2, 1), N(S + M +
      M) = b(5, 2), N(S + M + M + M) = b(8, 5), N(S + M + M + M + M) = b(11, 7), where
      M is the mechanism tangle, and S is the substrate tangle, that is the sum of O
      (outside tangle) and P (parent tangle). The advantage of this revisited model is
      that it faithfully models the fact that the recombination mechanism is the same
      during each event of recombination. This leads to new solutions for O and P, some
      of which are interesting from a biological viewpoint.

PMID- 9530018
TI  - An evolutionary analytical model of a complementary circular code simulating the
      protein coding genes, the 5' and 3' regions.
AB  - The self-complementary subset T0 = X0 [symbol: see text] ?AAA, TTT? with X0 =
      ?AAC, AAT, ACC, ATC, ATT, CAG, CTC, CTG, GAA, GAC, GAG, GAT, GCC, GGC, GGT, GTA,
      GTC, GTT, TAC, TTC? of 22 trinucleotides has a preferential occurrence in the
      frame 0 (reading frame established by the ATG start trinucleotide) of protein
      (coding) genes of both prokaryotes and eukaryotes. The subsets T1 = X1 [symbol:
      see text] ?CCC? and T2 = X2 [symbol: see text] ?GGG? of 21 trinucleotides have a
      preferential occurrence in the shifted frames 1 and 2 respectively (frame 0
      shifted by one and two nucleotides respectively in the 5'-3' direction). T1 and
      T2 are complementary to each other. The subset T0 contains the subset X0 which
      has the rarity property (6 x 10(-8) to be a complementary maximal circular code
      with two permutated maximal circular codes X1 and X2 in the frames 1 and 2
      respectively. X0 is called a C3 code. A quantitative study of these three subsets
      T0, T1, T2 in the three frames 0, 1, 2 of protein genes, and the 5' and 3'
      regions of eukaryotes, shows that their occurrence frequencies are constant
      functions of the trinucleotide positions in the sequences. The frequencies of T0,
      T1, T2 in the frame 0 of protein genes are 49, 28.5 and 22.5% respectively. In
      contrast, the frequencies of T0, T1, T2 in the 5' and 3' regions of eukaryotes,
      are independent of the frame. Indeed, the frequency of T0 in the three frames of
      5' (respectively 3') regions is equal to 35.5% (respectively 38%) and is greater
      than the frequencies T1 and T2, both equal to 32.25% (respectively 31%) in the
      three frames. Several frequency asymmetries unexpectedly observed (e.g. the
      frequency difference between T1 and T2 in the frame 0), are related to a new
      property of the subset T0 involving substitutions. An evolutionary analytical
      model at three parameters (p, q, t) based on an independent mixing of the 22
      codons (trinucleotides in frame 0) of T0 with equiprobability (1/22) followed by
      t approximately 4 substitutions per codon according to the proportions p
      approximately 0.1, q approximately 0.1 and r = 1 - p - q approximately 0.8 in the
      three codon sites respectively, retrieves the frequencies of T0, T1, T2 observed
      in the three frames of protein genes and explains these asymmetries. Furthermore,
      the same model (0.1, 0.1, t) after t approximately 22 substitutions per codon,
      retrieves the statistical properties observed in the three frames of the 5' and
      3' regions. The complex behaviour of these analytical curves is totally
      unexpected and a priori difficult to imagine.

PMID- 9530019
TI  - The heart of the matter: noninvasive coronary artery imaging.

PMID- 9530020
TI  - Measuring professional quality in radiology.

PMID- 9530021
TI  - The measure of professional quality in radiology.

PMID- 9530022
TI  - Reengineering a radiology department in an academic institution.
AB  - OBJECTIVE: A 1-year program was undertaken in conjunction with an outside
      consultant to cut nonphysician labor expenses by 15%, cut nonlabor expenses by
      10%, and improve all service parameters in an academic radiology department.
      MATERIALS AND METHODS: A steering committee decided on five major goal teams:
      improve report turnaround time and improve patient throughput, increase the
      efficiency of performance and improve the quality of radiologic examinations,
      decrease the cost of each examination, improve charge capture, and improve the
      perception of the department. The goal teams met at least every 2 weeks, made
      presentations to the steering committee at midyear, and were then disbanded. The
      steering committee implemented changes in the second half of the year and
      continues to meet every 2 weeks. Data were obtained from the radiology
      information system, financial statements, and surveys. RESULTS: In the first
      year, report turnaround time decreased from 157 hr to 83 hr (and to 46 hr at 2
      years), the efficiency of performing examinations (according to our criteria)
      improved from 64% to 80%, the quality of examinations improved, labor costs were
      reduced by 5% (and by 11% at 2 years), nonlabor costs were reduced by 14% (and by
      31% at 2 years), cost per examination was reduced by 10% (and by 16% at 2 years),
      increased charge capture resulted in an annual increase in professional fees of
      at least $110,000, and the perception of the department by referring clinicians
      improved. CONCLUSION: It is possible to simultaneously cut expenses and improve
      service. To gauge progress, objective parameters that can be measured easily are
      necessary.

PMID- 9530023
TI  - Trends in the use of radiology with inpatients: what has changed in a decade?
AB  - OBJECTIVE: Our goal was to evaluate trends in the use of radiology with
      inpatients in the 10-year period of 1984-1993. MATERIALS AND METHODS: We
      retrospectively reviewed administrative data from a 751-bed, tertiary care
      hospital between October 1, 1983, and September 30, 1993 (Fiscal years 1984
      1993). We coded each study by imaging technique: CT, MR imaging, sonography,
      nuclear medicine, or conventional studies (plain films and fluoroscopy).
      Echocardiography, cardiac catheterization, and angioplasty procedures were
      omitted. The number of admissions per year was adjusted for severity of disease
      (case-mix-adjusted admission [CMA]). We used relative value units to evaluate
      workload changes during the study period. We assessed significance of trends
      using linear regression analysis. RESULTS: The total number of imaging studies
      per CMA decreased during the study period (p = .0001). This was due to a decrease
      in the number of conventional studies (p = .0001) and sonograms per CMA (p =
      .02), despite significant increases in the numbers of CT (p = .005) and MR
      imaging (p = .0001) studies per CMA. No significant change existed in the number
      of nuclear medicine studies per CMA (p = .11). The global, professional, and
      technical relative value units per CMA rose during the latter half of the study.
      CONCLUSION: The overall number of imaging studies per CMA decreased during the
      decade, despite a significant rise in the use of CT and MR imaging, suggesting
      that these new imaging techniques are replacing older ones. To control further
      increases in overall imaging costs, priority should be placed on understanding
      the patterns of use for CT and MR imaging techniques and curbing their
      inappropriate use.

PMID- 9530024
TI  - Perceptual errors and negligence.
AB  - Radiologic errors continue to be made at a rate that has changed little over the
      past 50 years, despite a variety of methods that have been proposed to reduce
      such errors. Many of these methods, as well as other steps that can be taken to
      decrease errors, are described elsewhere [6, 31, 32]. However, the question of
      whether a missed radiographic diagnosis constitutes malpractice has confounded
      radiologists, patients, referring physicians, attorneys, jurors, and judges for
      decades, and it is not likely that the question will be resolved to the
      satisfaction of any of these parties in the foreseeable future. Against this
      backdrop, radiologists continue to be subjected to malpractice litigation more
      for missing radiographic diagnoses than for any other reason. Moreover,
      radiologists who are sued for missing diagnoses are likely to have more
      indemnification paid on their behalf to satisfy a settlement or adverse jury
      verdict than for any other malpractice allegation. Assuredly, it is difficult to
      defend a radiologist who has failed to perceive a radiographic abnormality that
      in retrospect can be readily perceived by medical and nonmedical observers alike.
      Nonetheless, solid defense-supporting data are available that, at times, can be
      presented to a jury successfully to achieve vindication for a defendant
      radiologist. These data include statistics regarding the frequency of errors
      committed by radiologists and other physicians during the course of ordinary
      everyday practice, the factors that cause varying conspicuity of radiographic
      densities, the limitations of normal human visual perception, and evidence that
      the process by which the radiologist originally rendered the interpretation was
      free of deficiency.

PMID- 9530025
TI  - A radiologist's visit to Ecuador.

PMID- 9530026
TI  - MR hydrography: theory and practice of static fluid imaging.

PMID- 9530027
TI  - Detection of coronary stenoses on source and projection images using three
      dimensional MR angiography with retrospective respiratory gating: preliminary
      experience.
AB  - OBJECTIVE: Our objective was to study the ability of three-dimensional MR
      angiography with retrospective respiratory gating to reveal stenoses in proximal
      coronary arteries on source and projection images. CONCLUSION: Proximal coronary
      artery stenoses can be identified using three-dimensional MR angiography with
      retrospective respiratory gating, both with projection images and on source
      images alone. Reasons for missed lesions included collateral vessels and
      retrograde flow distal to complete occlusion and volume averaging of vessels with
      adjacent structures. Causes of false-positive interpretations included small foci
      of decreased signal intensity distal to complete occlusion, partial volume
      effects on individual partitions, and regions of distal vessels leaving the
      imaging plane.

PMID- 9530029
TI  - Curved multiplanar reconstructions for the evaluation of contrast-enhanced
      electron beam CT of the coronary arteries.
AB  - OBJECTIVE: We investigated the applicability of curved multiplanar
      reconstructions for the evaluation of contrast-enhanced electron beam CT scans of
      the coronary arteries. SUBJECTS AND METHODS: Thirty-two patients (43-72 years
      old; mean age, 58 years old) underwent electron beam CT. After injection of i.v.
      contrast medium, 40 axial cross sections of the heart were acquired, triggered to
      the ECG during breath-hold (3-mm slice thickness, 1-mm overlap). Curved
      multiplanar reconstructions were obtained separately for each coronary artery.
      The reconstructions were independently evaluated by two investigators for the
      presence of high-grade stenoses and occlusions. The results were then compared
      with coronary angiography results, of which the two investigators had been
      unaware. RESULTS: Because of degraded image quality, 15 (12%) of the 128 vessels
      (left main, left anterior descending, left circumflex, and right coronary
      arteries in 32 patients) were excluded from evaluation. In the remaining 113
      vessels, 16 (89%) of 18 high-grade stenoses and occlusions were correctly
      detected (89% sensitivity). Absence of significant stenosis was correctly
      detected in 87 (92%) of 95 vessels (92% specificity). The negative and positive
      predictive values were 98% and 67%, respectively. CONCLUSION: Curved multiplanar
      reconstructions are useful in the evaluation of contrast-enhanced electron beam
      CT scans of coronary arteries.

PMID- 9530028
TI  - Measuring the diameter of coronary arteries on MR angiograms using spatial
      profile curves.
AB  - OBJECTIVE: The spatial profile curve of the nuclear MR intensity across the short
      axis of a coronary artery in an MR angiogram results in a gradual up-and-down
      slope lacking sharp definition, which indicates that display parameters may
      influence edge recognition. Therefore, our study was designed to determine the
      appropriate window setting and to devise a method of accurately measuring the
      diameter or width of the artery independent of window parameters. CONCLUSION: The
      diameter of a coronary artery measured on MR coronary arteriography significantly
      varied with experimentally selected display parameters. When compared with the
      diameter on contrast-enhanced coronary arteriograms, the window center on MR
      angiograms at the midpoint between the peak intensity of the intravascular lumen
      and the background intensity and the window width of a quarter or a half of the
      intensity difference between the two were proven to be appropriate. The
      angiographic diameter corresponded to the diameter obtained at 65% +/- 9% of the
      peak intensity on the spatial profile curve across the short-axis MR coronary
      angiogram. Accordingly, 65% of the peak intensity indicates the diameter of the
      coronary artery. Thus, the intensity profile curve independent of the window
      setting provided a new method for measurement of the diameter of the coronary
      artery.

PMID- 9530030
TI  - Noninvasive coronary artery imaging using CT and MR imaging.

PMID- 9530032
TI  - Diagnostic impact of four postprocessing techniques in evaluating contrast
      enhanced three-dimensional MR angiography.
AB  - OBJECTIVE: The purpose of this study was to determine the added diagnostic value
      of various three-dimensional (3D) data viewing techniques when analyzing contrast
      enhanced 3D MR angiography. MATERIALS AND METHODS: Twenty patients (mean age, 62
      years) with symptomatic peripheral vascular disease were assessed with breath
      hold, contrast-enhanced 3D MR angiography and catheter angiography, which served
      as the standard of reference. After an initial interpretation of the 3D MR
      angiographic data sets based only on standardized maximum intensity projections
      (MIP), the diagnostic gain of the stepwise addition of interactive multiplanar
      reformations, shaded-surface displays (SSD), and virtual intraarterial endoscopy
      (VIE) images was calculated. Time required for each step of postprocessing was
      measured. RESULTS: Pathologic changes were revealed by catheter angiography in 60
      vascular segments (50 severe stenoses, seven aneurysms, and three occlusions).
      The average postprocessing times were MIP, 8 min (range, 5-12 min); multiplanar
      reformations, 9 min (range, 3-11 min); SSD, 15 min (range, 8-25 min); and VIE, 40
      min (range, 18-63 min). Addition of multiplanar reformations to MIPs resulted in
      the greatest gain of diagnostic accuracy, from 92% to 96%, and diagnostic
      confidence. When analysis was based on all four techniques, receiver operating
      characteristic curve analysis revealed only minimal improvements in diagnostic
      confidence, whereas diagnostic accuracy remained unchanged at 96%. CONCLUSION:
      Accurate and time-effective analysis of contrast-enhanced 3D MR angiography
      should be based on MIP algorithms and multiplanar reformations. Additional
      evaluation with VIE or SSD techniques is time-consuming and provides little
      diagnostic gain.

PMID- 9530031
TI  - Metastatic cardiac calcification in a patient with chronic renal failure who was
      undergoing hemodialysis: radiographic and CT findings.

PMID- 9530033
TI  - Value of CT angiography for postoperative assessment of patients with iliac
      artery aneurysms who have received endovascular grafts.
AB  - OBJECTIVE: The purpose of the study was to assess the usefulness of CT
      angiography for follow-up of patients with iliac artery aneurysms who have
      undergone endovascular treatment. SUBJECTS AND METHODS: Twelve patients with
      iliac artery aneurysms (10 true aneurysms and two pseudoaneurysms) were examined
      with CT angiography within 1 week of receiving transfemorally placed endovascular
      grafts. All patients underwent follow-up CT angiography from 3 to 30 months
      (mean, 11 months) later. Follow-up CT angiography at 6 months or later (mean, 14
      months) was also available in 10 patients. All studies were obtained after i.v.
      contrast administration using 3-mm collimation, 1.6-2.0 pitch, 2-mm retrospective
      reconstruction, and with subsequent three-dimensional rendering and multiplanar
      reformation. The shape and patency of the graft, perigraft thrombosis, and the
      size of the aneurysm were assessed. RESULTS: All grafts remained patent and
      without deformity. Complete thrombosis of the aneurysm was shown by initial
      postoperative CT angiography in 11 patients and confirmed by follow-up studies. A
      single case of a perigraft leak was revealed by CT angiography and confirmed by
      follow-up angiography. No aneurysm showed change in size at late follow-up.
      CONCLUSION: CT angiography is an accurate method for evaluating endovascular
      devices. CT angiography can be used as a primary technique for follow-up of
      patients who have undergone endovascular repair of iliac aneurysms.

PMID- 9530034
TI  - Measuring carotid artery stenosis using CT angiography: the dilemma of
      artifactual lumen eccentricity.
AB  - OBJECTIVE: This study assesses artifactual luminal distortion, or eccentricity,
      that affects measurement of stenosis on CT angiography performed with a variety
      of helical protocols. MATERIALS AND METHODS: A 32-vessel carotid artery phantom
      was built with five known grades of stenoses (25%, 50%, 75%, 88%, and 94%) and
      three lengths of stenosis (1, 3, and 5 mm). This phantom was scanned with
      conventional and 1.0-, 1.5-, and 2.0-pitch helical CT with slice thicknesses of
      2, 4, and 8 mm, and three vessel orientations: parallel, 45 degrees oblique, and
      perpendicular to the z-axis. Oblique multiplanar reconstruction was performed
      with the latter two vessel orientations to produce images similar to the parallel
      to z-axis orientation. The cross-sectional images were then used to measure the
      maximum and minimum (longest and shortest) luminal diameters in and out of each
      stenosis at a computer workstation by a single investigator who was unaware of
      the scanning technique. Percentage of stenosis was assessed by three methods:
      cross-sectional area in and out of the stenosis, maximum diameter out of stenosis
      and minimum in stenosis (North American Symptomatic Carotid Endarterectomy Trial
      method), and minimum diameter in and out of the stenosis. Comparisons were made
      with the gold standard using the equation (measured percentage of stenosis-actual
      percentage of stenosis) based on known luminal diameters of the phantom. Luminal
      eccentricity was assessed for each of the vessels and scanning parameters as a
      ratio of minimum to maximum diameters. RESULTS: All three methods of measuring
      stenoses were strongly affected by luminal eccentricity. The North American
      Symptomatic Carotid Endarterectomy Trial method overestimated percentage of
      stenosis an average of 1.64%. The most accurate results were obtained when using
      the minimum diameter in and out of the stenoses (-0.45% from the gold standard).
      Eccentricity was significantly greater in stenoses than in normal lumen (p <
      .0001) and when the vessels were oriented perpendicular to the z-axis (p =
      .0003). A progressive increase in eccentricity was seen in the 4- and 8-mm slice
      thicknesses and the 3- and 5-mm-long stenoses (p < .001; p < .001). CONCLUSION:
      Artifactual luminal eccentricity has significant implications for measuring
      percentage of stenosis revealed by CT angiography. Eccentricity increases in
      longer stenoses, thicker slices, and vessels oriented perpendicular to the z
      axis. With CT angiography, measurement of minimum diameters in and out of a
      stenosis provides the most accurate assessment of percentage of stenosis.

PMID- 9530035
TI  - Axillary vein puncture over the second rib.

PMID- 9530036
TI  - Variability in the detection of enlarged mediastinal lymph nodes in staging lung
      cancer: a comparison of contrast-enhanced and unenhanced CT.
AB  - OBJECTIVE: Because CT protocols for staging lung cancer vary and little
      information exists regarding the diagnostic importance of using i.v. contrast
      material, our intent was to evaluate intra- and interobserver agreement in the
      detection of enlarged mediastinal lymph nodes, comparing i.v. contrast-enhanced
      and unenhanced CT. SUBJECTS AND METHODS: Fifty patients with known or suspected
      bronchogenic carcinoma underwent unenhanced thoracic CT followed by contrast
      enhanced CT. Three observers noted enlarged lymph nodes (> 10 mm in the short
      axis) and assigned the enlarged nodes to American Thoracic Society nodal station
      designations. Enlarged lymph nodes were grouped two ways: by assigning the exact
      number of enlarged lymph nodes found (zero, one, two, three, four or more), and
      by assigning whether at least one, or no, enlarged mediastinal lymph nodes were
      found at a station ("one or none"). Agreement levels were determined for inter-
      and intraobserver interpretations using weighted kappa statistics and the McNemar
      test. RESULTS: The number of enlarged lymph nodes with enhanced CT was 11% higher
      than on unenhanced studies (418 versus 377; p = .044). Numbers of enlarged lymph
      nodes were different for five stations; however, the numbers were small except
      for the right upper paratracheal station (2R) (contrast-enhanced, 68 enlarged
      lymph nodes; unenhanced, 44 enlarged lymph nodes; p = .014). With regard to all
      stations together, intraobserver agreement between contrast-enhanced and
      unenhanced studies was almost perfect (kappa range, .85-.94), and no difference
      was found for any observer in the proportion of patients with at least one
      enlarged lymph node. Interobserver agreement was substantial or almost perfect
      for the total number of enlarged lymph nodes. For specific stations, the lowest
      kappa value was .48 at 2R. One observer reported more patients with at least one
      enlarged lymph node with contrast enhancement at station 2R (p = .031). Greater
      agreement existed between two observers at station 2R with contrast enhancement
      versus no enhancement (kappa = .85 versus .48; p = .02). Conclusions matched, and
      calculations of estimated kappa values gave similar results for determination of
      the specific number of enlarged lymph nodes at a station and the "one or none"
      category. CONCLUSION: We found high agreement for intra- and interobserver
      interpretations for contrast-enhanced and unenhanced CT, although contrast
      enhanced CT revealed more enlarged lymph nodes, especially at station 2R.

PMID- 9530037
TI  - Ipsilateral spontaneous pneumothorax after rapid development of large thin-walled
      cavities in two patients who had undergone radiation therapy for lung cancer.

PMID- 9530038
TI  - Localized form of bronchioloalveolar carcinoma: FDG PET findings.
AB  - OBJECTIVE: The aim of our study was to describe 18F-fluorodeoxyglucose (FDG)
      positron emission tomography (PET) findings of a localized form of
      bronchioloalveolar carcinoma and to compare those findings with other cell types
      of lung cancer. SUBJECTS AND METHODS: FDG PET was performed in 48 patients with
      lung cancer. The patients had carcinomas of various cell types:
      bronchioloalveolar carcinoma (n = 9), squamous cell carcinoma (n = 11),
      adenocarcinoma (n = 22), and other cell types (n = 6). Using FDG PET, we compared
      peak standardized uptake values among the various cell types of lung cancer. CT
      and pathologic findings for patients with bronchioloalveolar carcinoma were also
      reviewed. RESULTS: Overall, 48 malignant tumors showed a mean peak standardized
      uptake value of 8.0 +/- 4.1. The mean peak standardized uptake value was 3.5 +/-
      2.2 for bronchioloalveolar carcinoma, 10.8 +/- 4.4 for squamous cell carcinoma,
      and 8.8 +/- 3.2 for adenocarcinoma. The mean peak standardized uptake value for
      bronchioloalveolar carcinoma was significantly lower than that for adenocarcinoma
      and squamous cell carcinoma (p < .001). On high-resolution CT scans,
      bronchioloalveolar carcinomas appeared as areas of ground-glass opacity (n = 4),
      as nodules (n = 2), as masses (n = 2), and as a ground-glass opacity plus
      consolidation (n = 1). On pathologic examination, bronchioloalveolar carcinomas
      were well differentiated, having moderate degrees of nuclear atypism, mild
      degrees of mitotic figure, desmoplasia, and necrosis. CONCLUSION: The localized
      form of bronchioloalveolar carcinoma shows significantly lower peak standardized
      uptake values than do other lung carcinomas. Thus, bronchioloalveolar carcinoma
      can be a potential cause of false-negative findings of malignancy on FDG PET
      scans. When bronchioloalveolar carcinoma is suggested, FDG PET results should be
      interpreted in combination with high-resolution CT findings.

PMID- 9530039
TI  - Lung involvement in angiotropic lymphoma: CT findings.

PMID- 9530040
TI  - Asymptomatic hydropneumothorax after therapeutic thoracentesis for malignant
      pleural effusions.
AB  - OBJECTIVE: The purpose of this study was to document in a historical cohort the
      incidence and clinical observations of pneumothorax ex vacuo after therapeutic
      thoracentesis for malignant pleural effusions in patients with underlying
      parenchymal lung disease. MATERIALS AND METHODS: Forty pneumothoraces resulted
      from 512 therapeutic thoracentesis performed for malignant pleural effusions over
      a 3-year period. Twenty-nine patients with pneumothoraces underwent catheter
      placement in the pleural space for treatment. Of these, 12 pneumothoraces
      resolved and 17 remained unchanged. We reviewed the charts of these 17 patients
      to document the cause of malignant pleural effusion, presence of underlying
      malignant parenchymal disease, volume of fluid aspirated, and improvement in
      symptoms. Clinical outcome was then evaluated, including size of residual
      pneumothorax, duration of catheter drainage, and reaccumulation of effusion.
      RESULTS: No patients' lungs reexpanded despite insertion of large-bore (16- to 35
      French) chest tubes. All had pneumothoraces that occupied at least 30% of the
      hemithorax; all were asymptomatic; all had underlying parenchymal disease and
      noncompliant lungs. Pleural effusion reaccumulated in all 17 after removal of the
      chest tube. CONCLUSION: A subgroup of patients with malignant lung parenchymal
      disease who undergo therapeutic thoracentesis will develop asymptomatic
      hydropneumothoraces due to poor lung compliance. These patients do not require
      further catheter drainage. Pleural effusion will reaccumulate in the residual
      space over a variable period of time.

PMID- 9530041
TI  - CT virtual bronchoscopy of simulated endobronchial lesions: effect of scanning,
      reconstruction, and display settings and potential pitfalls.

PMID- 9530042
TI  - Combined CT venography and pulmonary angiography: a new diagnostic technique for
      suspected thromboembolic disease.

PMID- 9530043
TI  - Chronic thromboembolic pulmonary hypertension: CT findings.

PMID- 9530044
TI  - Mammographic screening in women more than 64 years old: a comparison of 1- and 2
      year intervals.
AB  - OBJECTIVE: The purpose of our study was to determine if annual mammographic
      screening was superior to biennial screening in women more than 64 years old by
      examining differences in various prognostic indicators. MATERIALS AND METHODS: We
      reviewed the records of 119 consecutive women 65 years old and older with 120
      cases of breast cancer who had a previous normal screening evaluation for breast
      cancer that included mammography and physical examination 8-30 months before
      diagnosis. A search of the computerized tumor registry, clinical records, and
      breast imaging records from November 1988 to April 1995 provided our cases.
      Screening intervals were defined as 6-18 months (annual) and 19-30 months
      (biennial). Mammographic, histologic, and clinical features were reviewed.
      Disease severity (DS) levels were assigned to each tumor as follows: DS-1
      included minimal disease (ductal carcinoma in situ [TisNO], T1aN0, and T1bN0
      tumors), DS-2 included all T1cN0 tumors, DS-3 included tumors larger than 2 cm in
      diameter with lymph nodes that were negative for cancer, and DS-4 included all
      metastatic disease. Statistically significant differences were calculated using
      the Wilcoxon rank sum test, Fisher's exact test, and the chi-square test.
      RESULTS: Ninety-three tumors were found in the group of patients who were
      annually screened, and 27 were found in the group of patients who were screened
      biennially. The women who underwent yearly screening mammography had
      significantly smaller invasive tumors (average, 10.7 mm; median, 9.5 mm versus
      16.5 mm and 15.0 mm, respectively; p = .0086). The women who were screened
      annually also had significantly less advanced disease than women screened
      biennially (annually screened patients versus biennially screened patients: DS-1,
      72% versus 44%; DS-2, 23% versus 37%; DS-3, 2% versus 11%; DS-4, 3% versus 7%; p
      = .0071). The group of patients screened annually had fewer cases of lymph node
      metastases (3% versus 8%; p = .12) and three times as many cases of ductal
      carcinoma in situ (22% versus 7%, p = .10). CONCLUSION: Annual screening
      mammography revealed significantly smaller tumors and less advanced cases of
      cancer than biennial screening, providing inferential support for annual
      mammographic screening of women more than 64 years old.

PMID- 9530045
TI  - Delayed development of enhancement in fat necrosis after breast conservation
      therapy: a potential pitfall of MR imaging of the breast.

PMID- 9530046
TI  - Percutaneous CT-guided catheter drainage of infected acute necrotizing
      pancreatitis: techniques and results.
AB  - OBJECTIVE: The objective of this paper was to assess the safety and efficacy of
      percutaneous catheter drainage for initial treatment of infected acute
      necrotizing pancreatitis. MATERIALS AND METHODS: Thirty-four patients with acute
      necrotizing pancreatitis shown with contrast-enhanced CT were treated for sepsis
      with percutaneous catheter drainage. Extent of necrosis was less than 30% in 10
      cases, 30-50% in 10 cases, and greater than 50% in 14 cases. Fourteen patients
      had central necrosis. Eighteen patients were critically ill with multiorgan
      failure. RESULTS: Sixteen (47%) of the 34 patients were cured with only
      percutaneous catheter drainage, including four (29%) of the 14 patients with
      central gland necrosis and 12 (60%) of the 20 with body-tail necrosis. Sepsis was
      controlled (defervescence of fever and return of WBC to normal) in an additional
      nine patients, allowing elective pancreatic surgery for control of pancreatic
      duct fistula. Eight patients failed to show clinical improvement after drainage
      and required necrosectomy. No patient experienced catheter-related complications.
      Mortality was 12% (all four deaths occurred after necrosectomy because of
      multiorgan failure). CONCLUSION: Percutaneous catheter drainage is a safe and
      effective technique for treating infected acute necrotizing pancreatitis.
      Overall, sepsis was controlled in 74% of patients, permitting elective surgery
      for treatment of pancreatic fistula, and 47% of patients were cured with no
      surgery required. No catheter-related complications occurred.

PMID- 9530047
TI  - Percutaneous drainage of pancreatic necrosis: is it ecstasy or agony?
AB  - The above comments are meant to help the reader further analyze the fine study of
      Freeny et al. [1]. To my knowledge, this is the first series to specifically
      define its patients correctly as having pure pancreatic necrosis. This work
      represents a thorough analysis of a difficult problem and points out how to treat
      these patients if one wants to be successful. This template is important to
      radiologists who wish to get involved with this type of patient. What Freeny et
      al. truly describe is the agony and ecstasy involved with this difficult
      undertaking. Radiologists can obtain a lot of satisfaction in taking care of this
      type of patient, but they and the referring physicians must be committed. The
      patient, the referring physician, and the radiologist must also face the agony in
      dealing with the illness. They must be ready to handle the number of catheters,
      the number of catheter changes, the number of CT scans, and the duration of
      drainage. In some cases percutaneous drainage will work; in some cases it is the
      only alternative for a patient with this disease. In other cases a catheter or
      two can be placed, but they might not be as beneficial to the patient as surgery.
      Clearly, percutaneous drainage of pancreatic necrosis can be done, and
      radiologists must work with their clinical colleagues to decide whether it is in
      the patient's best interest.

PMID- 9530048
TI  - Patterns of neoplastic spread in colorectal cancer: implications for surveillance
      CT studies.
AB  - OBJECTIVE: This study was performed to assess patterns of metastatic disease
      shown on CT in colorectal cancer and to determine the diagnostic yield of routine
      pelvic CT in follow-up surveillance. MATERIALS AND METHODS: Pathology records and
      3073 CT studies of 1119 patients with colorectal cancer were retrospectively
      reviewed. Primary tumor site, site of abdominal or pelvic metastases (liver,
      peritoneum, lymph nodes, local recurrence, or other), and incidental
      nonmetastatic pelvic disease were recorded. The superior iliac crests were
      considered the border between the abdomen (above) and the pelvis (below).
      RESULTS: Metastatic disease was present in 34% (1040/3073) of all CT studies: 33%
      (1007/3073) in the abdomen and 7% (227/3073) in the pelvis. Six percent
      (194/3073) of studies had metastases in both abdomen and pelvis. Forty-one
      percent (404/991) of studies showing abdominal primary colonic tumors showed
      metastatic disease: 40% (400/991) in the abdomen and 8% (78/991) in the pelvis.
      Four studies (0.4%; 4/991) in four different patients with abdominal primary
      colon tumors had isolated pelvic metastases; three of these were primary tumors
      of the cecum. Thirty-one percent (636/2082) of studies showing pelvic primary
      colonic tumors showed metastatic disease: 29% (607/2082) in the abdomen and 7%
      (149/2082) in the pelvis. Twenty-nine studies (1%; 29/2082) in 26 patients with
      pelvic primary colonic tumors revealed isolated pelvic metastases. CONCLUSION: In
      colorectal tumors arising within the abdomen, pelvic metastases are uncommon and
      isolated pelvic metastases are rare. Routine pelvic CT performed in the follow-up
      surveillance of patients with colorectal cancer with primary tumors arising in
      the abdominal portion of the colon has a low diagnostic yield.

PMID- 9530049
TI  - Adjustable laparoscopic gastric band for the treatment of morbid obesity:
      radiologic evaluation.
AB  - OBJECTIVE: This article describes the radiographic appearance of a recently
      developed laparoscopically placed adjustable gastric band for the treatment of
      morbid obesity. The optimal technique for contrast evaluation of the device,
      complications associated with its use, and the technique for stoma adjustments
      are also discussed. SUBJECTS AND METHODS: Between May and December 1996, 23
      patients at our institution underwent laparoscopic placement of adjustable
      silicone gastric bands for treatment of morbid obesity. All patients underwent a
      barium upper gastrointestinal series before surgery, 1 day after band placement,
      at variable intervals when each patient returned for band adjustment, and at 1
      year. RESULTS: Unlike the case in other gastric weight loss procedures, the
      optimal patient position for contrast evaluation of gastric bands was
      anteroposterior or slightly right posterior oblique. Twenty-one of 23 patients
      had no complications shown on the postoperative upper gastrointestinal series.
      Stoma size was approximately 3-8 mm, and most patients showed delayed esophageal
      emptying without obstruction. Two patients had herniation of the stomach through
      the gastric band with pouch enlargement, resulting in obstruction and the need
      for additional surgery. We saw no leaks or band erosions. Nineteen stoma
      adjustments were performed in 13 patients. One patient had an inverted port that
      could not be accessed for adjustment. CONCLUSION: As adjustable gastric bands
      become more widely used, radiologists need to be familiar with the radiographic
      appearance of the devices, the complications associated with their use, and the
      optimal patient positioning for contrast evaluation. Radiologists may also be
      involved with band adjustment to decrease or increase the stoma size and
      therefore need to understand the technique and potential difficulties of
      adjusting the stoma.

PMID- 9530050
TI  - Helical CT of the spleen.

PMID- 9530051
TI  - Hepatocellular carcinoma in North America: a multiinstitutional study of
      appearance on T1-weighted, T2-weighted, and serial gadolinium-enhanced gradient
      echo images.
AB  - OBJECTIVE: The purpose of this study was to define the common appearances of
      hepatocellular carcinoma (HCC) in patients in North America by analyzing T1
      weighted, T2-weighted, and serial gadolinium-enhanced gradient-echo images
      interpreted by radiologists at multiple institutions in North America. MATERIALS
      AND METHODS: One hundred thirteen consecutive patients with HCC from eight
      institutions were included in this retrospective case series. Inclusion criteria
      included MR imaging examinations performed on 1.5-T MR imagers using T1-weighted
      breath-hold spoiled gradient-echo images, T2-weighted images, and serial
      gadolinium-enhanced spoiled gradient-echo images. Diagnosis was established by
      histology in all patients. Images were analyzed retrospectively for lesion count,
      lesion diameter as less than or equal to 1.5 cm and greater than 1.5 cm, and
      signal intensity, by individual experienced radiologists at each institution.
      RESULTS: We found 354 HCC lesions in the 113 patients. Tumors were solitary in 63
      patients, multifocal in 45 patients, and diffuse in five patients. Lesion
      appearance on combined T1-weighted, T2-weighted, and immediate gadolinium
      enhanced spoiled gradient-echo images was as follows: 102 lesions (29%) were
      hypointense on T1-weighted images, were hyperintense on T2-weighted images, and
      exhibited diffuse heterogeneous enhancement; 52 lesions (15%) were isointense on
      both T1- and T2-weighted images and exhibited diffuse homogeneous enhancement
      (all of these lesions measured < or = 1.5 cm in diameter); 50 lesions (14%) were
      hypointense on T1-weighted images, were hyperintense on T2-weighted images, and
      exhibited diffuse homogeneous enhancement; 33 lesions (9%) were hypointense on T1
      weighted images, were hyperintense on T2-weighted images, and exhibited
      predominantly peripheral rim enhancement; and 27 lesions (8%) were hypointense on
      T1-weighted images, were isointense on T2-weighted images, and exhibited diffuse
      homogeneous enhancement. The remaining 90 lesions showed less common patterns.
      The appearance of HCCs greater than 1.5 cm and of HCCs less than or equal to 1.5
      cm was significantly different (p = .001). The appearance of histologically
      proven HCCs is separately described. CONCLUSION: The combination of hypointensity
      on T1-weighted images, hyperintensity on T2-weighted images, and diffuse
      heterogeneous enhancement was the most common appearance of HCC on MR images in a
      multiinstitutional patient population in North America. Small HCCs measuring less
      than or equal to 1.5 cm were frequently isointense on both T1-weighted and T2
      weighted images and may be detected on immediate gadolinium-enhanced images only
      as diffuse homogeneously enhancing lesions.

PMID- 9530052
TI  - Percutaneous treatment of small hepatic tumors by an expandable RF needle
      electrode.
AB  - OBJECTIVE: The aim of this study was to evaluate the usefulness of expandable RF
      needle electrodes in the treatment of hepatic cancer. SUBJECTS AND METHODS:
      Thirty-seven patients, 23 of whom had 26 hepatocellular carcinoma nodules and 14
      of whom had 19 hepatic metastatic nodules, underwent treatment by RF interstitial
      thermal ablation with expandable needle electrodes. Forty-five tumor nodules were
      treated in 64 RF interstitial thermal ablation sessions with 83 needle electrode
      insertions. The mean diameter of the tumor nodules was 2.5 cm (range, 1.1-3.5
      cm). Immediate posttreatment tumor necrosis was evaluated by dynamic CT in all
      cases. Two patients with hepatocellular carcinoma and three patients with
      metastases underwent surgical resection 20-60 days after RF treatment. The
      remaining 32 patients were followed up clinically. RESULTS: The mean number of RF
      interstitial thermal ablation sessions to complete tumor nodule treatment was
      1.4. Mean number of needle electrode insertions was 1.8. No complications were
      observed. Posttreatment dynamic CT showed a completely nonenhancing area in the
      site of the treated tumor in 44 of 45 cases. The remaining patient with
      metastatic disease had persistent enhancing tissue. Histology showed complete
      necrosis in four treated tumor nodules and residual viable cancer in one. Twenty
      one patients with hepatocellular carcinoma were followed up for 6-19 months
      (mean, 10 months). Of these patients, six showed recurrences and 15 remained
      apparently disease-free. Two patients died, one from advanced cancer and one from
      other causes. Eleven patients with hepatic metastases were followed up for 7-20
      months (mean, 12 months). Of these patients, nine showed recurrent disease and
      only two remained apparently disease-free. Two patients died from disseminated
      disease. CONCLUSION: RF interstitial thermal ablation of hepatic tumor by
      expandable needle electrodes is a safe and effective technique. Local ablation of
      tumors not exceeding 3.5 cm in diameter is achieved in a short time without
      complications.

PMID- 9530053
TI  - Ablation of liver tumors using percutaneous RF therapy.

PMID- 9530054
TI  - Characterization of hepatic lesions by perfusion-weighted MR imaging with an
      echoplanar sequence.
AB  - OBJECTIVE: The purpose of this study was to examine the usefulness of perfusion
      weighted MR imaging with a single-shot gradient echoplanar sequence in
      characterizing hepatic tumors. SUBJECTS AND METHODS: Perfusion-weighted imaging
      was performed in 61 patients with 91 confirmed hepatic tumors (14 hemangiomas, 19
      metastases, and 58 hepatocellular carcinomas). The perfusion-weighted imaging was
      started at the time of administration of 0.1 mmol/kg of gadolinium, and images
      were continuously obtained every 2 sec for 88 sec. Time-intensity curves for all
      the tumors were created for quantitative analysis. Patterns of enhancement were
      also evaluated. RESULTS: Changes in signal intensity that occurred throughout
      examination differed in three types of tumor. Transient signal intensity
      decreases in the perfusion phase significantly differed in three types of tumors
      (46% in hepatocellular carcinoma, 48% in hemangioma, and 15% in metastasis, p <
      .05 for hepatocellular carcinoma versus metastasis and for hemangioma versus
      metastasis). Signal intensity recovered rapidly for hepatocellular carcinoma and
      metastasis, whereas recovery was slower for hemangioma. Final signal intensity
      recovery was 94% in hepatocellular carcinoma, 91% in metastasis, and 54% in
      hemangioma compared with their initial signal intensities. (p < .05 for
      hepatocellular carcinoma versus hemangioma and for hemangioma versus metastasis.)
      The enhancement patterns also differed in three types of tumor. CONCLUSION:
      Perfusion-weighted imaging with a gradient echoplanar sequence provides real-time
      mapping of many points along the enhancement profile curves because of its
      excellent temporal resolution. Therefore, it accurately characterizes hepatic
      tumors based on their different negative-enhancement patterns.

PMID- 9530055
TI  - Percutaneous treatment of liver abscesses: needle aspiration versus catheter
      drainage.
AB  - OBJECTIVE: This study was designed to determine and compare the efficacy of
      sonographically guided percutaneous needle aspiration and percutaneous catheter
      drainage in the treatment of liver abscesses. SUBJECTS AND METHODS: In a
      randomized study, 50 patients (38 males and 12 females; age range, 2-72 years;
      average age, 35 years) with liver abscesses (amebic, 20; pyogenic, 11;
      indeterminate, 19) underwent either percutaneous needle aspiration (n = 25) or
      catheter drainage (n = 25) along with appropriate antimicrobial therapy. In
      patients assigned to the needle aspiration group, an 18-gauge needle was used to
      aspirate the abscess cavity. Repeated aspiration was attempted only once in each
      patient not responding to the first aspiration; nonresponse to the second
      aspiration was considered failure of treatment, and these patients were given
      catheter drainage (however, these patients were not included in the catheter
      drainage group). For catheter drainage, 8- to 12-French catheters were introduced
      into the abscess cavity using the Seldinger technique. In patients with multiple
      abscesses (seven in aspiration group and five in catheter group), all the
      abscesses except those smaller than 3 cm were subjected to percutaneous
      treatment. Patients were followed up to assess the outcome of the percutaneous
      treatment, length of hospital stay, and development of any complications.
      Sonography was performed every third day during hospitalization. After discharge
      of the patient, periodic clinical and sonographic examinations were done until
      total resolution of abscesses was achieved. RESULTS: Although percutaneous needle
      aspiration was successful in only 15 (60%) of the 25 patients after one (n = 11)
      or two (n = 4) aspirations, catheter drainage was curative in all 25 patients
      (100%) (p < .05). Among the successfully treated patients, the average time for
      clinical improvement and the mean hospital stay were similar in the two treatment
      groups. Although the average time needed for a 50% reduction in the size of the
      abscess cavity was significantly (p < .05) greater in the aspiration group than
      in the catheter group (11 days versus 5 days), the average time taken for total
      resolution of abscess was the same (15 weeks) in both groups. No major
      complications were encountered. No relapse was documented on clinical and
      sonographic examination during follow-up, which ranged from 8 to 37 weeks.
      CONCLUSION: Our results show that percutaneous catheter drainage is more
      effective than needle aspiration in the treatment of liver abscesses. Needle
      aspiration, if limited to two attempts, has a high failure rate.

PMID- 9530056
TI  - Value of echo-enhanced Doppler sonography in evaluation of transjugular
      intrahepatic portosystemic shunts.
AB  - OBJECTIVE: The value of echo-enhanced color and power Doppler sonography in the
      evaluation of transjugular intrahepatic portosystemic shunts (TIPS) was assessed
      and compared with that of unenhanced Doppler sonography and portal angiography.
      SUBJECTS AND METHODS: In a prospective randomized trial, 31 shunts in 30 patients
      underwent unenhanced conventional color and power Doppler sonography and portal
      venography including pressure measurements. The patients were allocated to either
      echo-enhanced conventional color Doppler sonography or echo-enhanced power
      Doppler sonography. For echo enhancement, a galactose-based suspension was
      administered IV. Shunt stenoses, if present, were quantified by percentage of
      stenosis and correlated with angiography, which was the gold standard. The
      diagnostic confidence of unenhanced and echo-enhanced Doppler sonography was
      assessed using a visual analog scale. RESULTS: In the diagnosis of shunt
      occlusion, echo-enhanced Doppler sonography yielded a sensitivity and a
      specificity of 100% and 100%, respectively, compared with 100% and 89%,
      respectively, for unenhanced Doppler sonography. Our evaluation of
      hemodynamically significant stenoses (portosystemic gradient > or = 15 mm Hg)
      found echo-enhanced Doppler sonography to be superior to unenhanced Doppler
      sonography (sensitivity and specificity of 82% and 83%, respectively, compared
      with 64% and 80%, respectively). In the detection of a shunt stenosis based on
      morphologic criteria only, echo-enhanced Doppler sonography yielded a sensitivity
      and a specificity of 78% and 100%, respectively, compared with 47% and 50%,
      respectively, for unenhanced Doppler sonography. Power Doppler imaging did not
      improve diagnostic accuracy but did increase diagnostic confidence for unenhanced
      Doppler sonography compared with conventional color Doppler sonography. The
      diagnostic confidence for sonographic evaluation of TIPS was significantly (p <
      .001) increased and the variability of hemodynamic measurements was markedly
      decreased with echo-enhanced sonography. CONCLUSION: Echo-enhanced Doppler
      sonography provides images of TIPS like those of angiography and allows
      morphologic assessment of the shunts, complementary to the essential pulsed
      Doppler waveform analysis that would be performed in a more guided manner. Also,
      echo-enhanced Doppler sonography significantly increases the sensitivity and
      specificity in the diagnosis of shunt dysfunction. The high diagnostic confidence
      and the diminished variability of spectral Doppler measurements may improve
      acceptance of sonographic evaluation of TIPS. Echo-enhanced Doppler sonography is
      safe and effective and may reduce the instances in which TIPS sonographic
      surveillance is nondiagnostic, in which case angiographic assessment is required.

PMID- 9530057
TI  - Transjugular intrahepatic portosystemic shunts: improved evaluation with echo
      enhanced color Doppler sonography, power Doppler sonography, and spectral duplex
      sonography.
AB  - OBJECTIVE: We assessed the feasibility of contrast-enhanced color Doppler, power
      Doppler, and spectral duplex sonography for visualization and quantification of
      flow through transjugular intrahepatic portosystemic shunts (TIPS) in patients in
      whom the baseline sonographic evaluation was unsatisfactory. SUBJECTS AND
      METHODS: Thirty-three patients underwent color Doppler, power Doppler, and
      spectral duplex sonography after TIPS insertion or before TIPS revision (mean
      time interval +/- SD, 1 +/- 1 day). All sonograms were obtained before and after
      patients received echo-enhancing contrast material. Sonography was evaluated with
      regard to presence or absence of flow in the mid portion, portal segment, and
      hepatic segment of the shunt. The maximal peak velocity was measured in the mid
      portion of the shunt. For identifying and quantifying stenoses, the percentage of
      luminal diameter reduction was calculated at the tightest part of the shunt.
      Shunt angiography and measurements of portosystemic pressure gradients were
      independently evaluated and compared with the sonographic findings. RESULTS: Flow
      visualization on unenhanced color Doppler sonography was significantly improved
      through the use of power Doppler sonography and contrast-enhanced color Doppler
      and power Doppler sonography (p < .01). Between contrast-enhanced power Doppler
      and contrast-enhanced color Doppler sonography, a significant difference was
      found in the portal and hepatic segments (p < .05). All shunt stenoses (n = 8)
      and occlusions (n = 3) were revealed by power Doppler sonography, whereas color
      Doppler sonography failed to reveal six of eight stenoses. Compared with
      unenhanced sonography, the quality of spectral duplex sonography was improved in
      eight patients after contrast enhancement (p < .05). Maximal peak velocity ranged
      from 54 to 252 cm/sec (mean +/- SD, 132.7 +/- 52.1 cm/sec) in normal shunts and
      from 24.5 to 70.0 cm/sec (mean +/- SD, 45.0 +/- 18.9 cm/sec) in stenosed shunts.
      No correlation was found between maximal peak velocity and portosystemic pressure
      gradients (r = .28). CONCLUSION: Unenhanced power Doppler and contrast-enhanced
      color and power Doppler sonography can be helpful in the assessment of TIPS
      status in patients who previously underwent unsatisfactory sonography. These
      techniques may allow anatomic evaluation and quantification of shunt stenosis in
      most patients. Contrast enhancement may also considerably improve the quality of
      spectral duplex sonography.

PMID- 9530058
TI  - Pitfalls in the interpretation of MR cholangiopancreatography.

PMID- 9530059
TI  - Postnatal maturation of the sacrum and coccyx: MR imaging, helical CT, and
      conventional radiography.
AB  - OBJECTIVE: The purpose of this paper is to provide a detailed radiologic
      description of the postnatal developmental anatomy of the sacrum and coccyx as
      revealed by MR imaging, helical CT, and conventional radiography. MATERIALS AND
      METHODS: One hundred ten imaging examinations of the sacrococcygeal spine were
      performed in patients who were newborn to 30 years old. Imaging included
      conventional radiography (n = 63), three-dimensional gradient-recalled echo MR
      imaging (n = 10), and helical CT with sagittal and angled coronal reformations (n
      = 37). A detailed analysis was performed of the ossification and fusion of the
      primary and secondary ossification centers. RESULTS: The sacrum and coccyx were
      noted to develop from 58 to 60 sacral ossification centers and eight coccygeal
      centers, respectively. These centers were noted to ossify and fuse in an
      organized temporal pattern from the fetal period to the age of 30. CONCLUSION:
      The sacrum and coccyx are formed by a complex process that fuses primary and
      secondary ossification centers. Because the maturation process can be asymmetric,
      an understanding of this process may prove useful for distinguishing physeal
      plates from fracture lines.

PMID- 9530060
TI  - Cystic fibrosis: a system for assessing and predicting progression.
AB  - OBJECTIVE: This study presents a radiography-based database scoring changes over
      time in a large population of patients with cystic fibrosis. The purpose of this
      database is to provide comparison for groups of patients undergoing experimental
      treatment to assess effect of the treatment. The data may also be used to compare
      individuals with their age-matched cohorts with cystic fibrosis. MATERIALS AND
      METHODS: From 230 patients, 3038 chest radiographs were scored using the
      Brasfield system. The scores from radiographs from all the patients were
      individually plotted for age, and a single age-based severity curve was created.
      The age-based severity curve was compared with similar curves derived from
      pulmonary function studies of a subset of the same patient population. RESULTS:
      We found high inter- and intraobserver reliability. The difference between the
      observers averaged 1.3 Brasfield points, the scale of which ranges up to 25
      points. The age-based severity curve was presented as mean Brasfield scores
      versus age (birth to > 30 years) plotted with 95% confidence limits; the curve
      was also plotted in percentiles. The rate of decline of this curve was similar to
      the decline of pulmonary function studies in this patient population. CONCLUSION:
      The age-based curve, a structural anatomic parameter, differs from pulmonary
      function studies, which are functional. Thus the age-based severity curve
      provides an additional, independent basis for comparison between groups and
      individuals. It may be used for the initial assessment of lung disease and for
      gauging and predicting the rate of decline. The curve may be used as a long-range
      outcome criterion to evaluate new treatments in groups of patients with cystic
      fibrosis.

PMID- 9530061
TI  - CT appearance of clinically occult abdominal hemorrhage in children.

PMID- 9530062
TI  - Epidemic adenoviral lower respiratory tract infection in pediatric patients:
      radiographic and clinical characteristics.
AB  - OBJECTIVE: This retrospective study was undertaken to evaluate the radiographic
      and clinical findings of adenoviral lower respiratory infection during an
      epidemic period. CONCLUSION: Epidemic adenoviral pneumonia may mimic bacterial
      pneumonia on radiographs. Findings that include bilateral and multifocal
      involvement on chest radiographs, normal or decreased WBC associated with
      lymphocytosis, and progression of illness despite extensive antibiotic therapy,
      help to differentiate epidemic adenoviral from bacterial pneumonia.

PMID- 9530063
TI  - Imaging findings in COACH syndrome.

PMID- 9530064
TI  - Significance of fetal intracardiac echogenic foci in relation to trisomy 21: a
      prospective sonographic study of high-risk pregnant women.
AB  - OBJECTIVE: The aim of the study was to determine if an association exists between
      intracardiac echogenic foci in the second-trimester fetus and trisomy 21.
      SUBJECTS AND METHODS: Over a 2-year period, targeted fetal sonography was
      performed for various indications in 1593 second-trimester high-risk pregnant
      women. Presence or absence of echogenic foci was recorded for each fetus.
      Amniocentesis for karyotype analysis was performed in 901 subjects immediately
      after sonography. The findings of these 901 subjects formed the basis of this
      report. RESULTS: Intracardiac echogenic foci were present in the left ventricle
      of 24 (3%) of the 901 fetuses. Three (13%) of these 24 fetuses had trisomy 21; no
      chromosomal abnormalities were found in the other 21 fetuses. Karyotype analysis
      revealed trisomy 21 in 14 (2%) of the remaining 877 fetuses who did not exhibit
      intracardiac echogenic foci. The sensitivity, specificity, positive predictive
      values, and negative predictive values for intracardiac echogenic foci in
      predicting trisomy 21 were 18%, 98%, 13%, and 98%, respectively. The association
      of intracardiac echogenic foci and trisomy 21 was significant (p < .009) by the
      two-tailed Fisher's exact test. CONCLUSION: In a high-risk obstetric population,
      the association between fetal intracardiac echogenic foci and trisomy 21 was
      statistically significant. Therefore, women carrying fetuses with intracardiac
      echogenic foci should be informed of the statistical association with trisomy 21.

PMID- 9530065
TI  - Inflammatory disease of the jaw: appearance on reformatted CT scans.
AB  - OBJECTIVE: Before the development of dental CT reformatting software, much of the
      radiographic assessment of the mandible and maxilla was performed in the
      dentist's office using plain radiographs. The widespread use of dental
      reformatting software, however, has caused the radiologist to take a more active
      role in evaluating the jaw. Unfortunately, most radiologists have had little
      experience in this area, and many of the CT findings are undescribed. Our
      objective, therefore, was to determine the CT appearance of dental-related
      inflammatory disease of the jaw and to discuss the mechanisms causing such
      disease. MATERIALS AND METHODS: Reformatted CT scans of 400 patients referred for
      dental implant assessment were evaluated for abnormalities related to infection
      of dental origin, inflammation of dental origin, or both. The diagnosis was
      confirmed by surgery, clinical presentation, classic plain film appearance, or a
      combination of the three. RESULTS: The following disease processes were
      identified and described: periodontal lesions, periapical lesions, condensing
      osteitis, disuse bone atrophy associated with edentia, and maxillary sinus
      abnormalities associated with dental disease. CONCLUSION: Inflammatory diseases
      of the jaw and their sequelae are frequently seen on CT scans of patients
      referred for examination before dental implantation. Because radiologists now
      take an active role in evaluating the jaw, they need to become familiar with
      these findings.

PMID- 9530066
TI  - Normative measurements of orbital structures using CT.
AB  - OBJECTIVE: The purposes of this study were to establish criteria for the
      diameters of normal extraocular muscles, to determine the normal position of the
      globe as revealed by CT, and to investigate the effects of age and sex on these
      structures. SUBJECTS AND METHODS: Diameters of extraocular muscles, distance from
      the interzygomatic line to the posterior margin of the globe, width of the optic
      nerve-sheath complex, and length of the interzygomatic line were calculated for
      200 normal orbits of 100 patients on axial and direct coronal CT images. Effects
      of age and sex on muscle diameters and globe position were analyzed. RESULTS:
      Normal ranges for the diameters (mean +/- 2SDs) of extraocular muscles were
      medial rectus, 3.3-5.0 mm; lateral rectus, 1.7-4.8 mm; inferior rectus, 3.2-6.5
      mm; and superior group, 3.2-6.1 mm. The normal position of the globe was 9.4 mm
      behind the interzygomatic line (range, 5.9-12.8 mm). The mean diameters of the
      extraocular muscles and the length of the interzygomatic line in male patients
      were significantly larger than in female patients (p < .001). Statistically
      significant correlation was found between age and the diameters of the inferior
      and lateral rectus muscles (r = .32, p = .013; and r = .23, p = .048,
      respectively). CONCLUSION: Our results may be important in interpreting CT scans
      of the orbit because, to our knowledge, no reliable normative data exist
      regarding these orbital structures.

PMID- 9530067
TI  - MR imaging of abnormal parathyroid glands.

PMID- 9530068
TI  - What is the evidence-based specificity of colonoscopy in detecting precursors of
      colorectal cancer in average-risk asymptomatic individuals who are more than 50
      years old?

PMID- 9530069
TI  - What is the current recommended waiting time for performance of a
      gastrointestinal barium study after endoscopic biopsy of the upper or lower
      gastrointestinal tract?

PMID- 9530070
TI  - Has the previous recommendation of obtaining screening radiographs of the orbits
      to evaluate for possible metallic foreign bodies changed with low-field-strength
      MR imagers?

PMID- 9530071
TI  - How much lateral atlantodental interval asymmetry and atlantoaxial lateral mass
      asymmetry is acceptable on an open-mouth odontoid radiograph, and when is
      additional investigation necessary?

PMID- 9530072
TI  - The Roszler index.

PMID- 9530073
TI  - Malpractice issues in radiology: radiology reports.

PMID- 9530074
TI  - America's first radiologic malpractice suit: a Freudian slip?

PMID- 9530075
TI  - Percutaneous radiologic replacement of blocked nephrovesical stent.

PMID- 9530076
TI  - Paget's disease of bone in Japan.

PMID- 9530077
TI  - Qualities of a good radiology report.

PMID- 9530078
TI  - Importance of peer review immunity protection in resident evaluations.

PMID- 9530080
TI  - Isolated fallopian tube torsion.

PMID- 9530079
TI  - Pseudoaneurysm of the breast: the use of color Doppler sonography.

PMID- 9530081
TI  - Aggressive angiomyxoma of pelvic soft tissues: MR imaging appearance.

PMID- 9530082
TI  - A small-bowel enema artifact.

PMID- 9530083
TI  - Hemorrhagic presentation of untreated primary CNS lymphoma in a patient with
      AIDS.

PMID- 9530084
TI  - Primary granulocytic sarcoma of the duodenum: radiologic and endoscopic findings.

PMID- 9530085
TI  - The never-ending pas de deux. Focus on "capacitative Ca2+ entry is involved in
      cAMP synthesis in mouse parotid acini".

PMID- 9530086
TI  - Capacitative Ca2+ entry is involved in cAMP synthesis in mouse parotid acini.
AB  - Muscarinic receptor interaction leading to augmentation of isoproterenol
      stimulated cAMP accumulation in mouse parotid acini involves Ca2+ (28). The
      effectiveness of capacitative Ca2+ entry and intracellular Ca2+ release on this
      response was determined in time course studies by using three independent tools
      to manipulate the free intracellular Ca2+ concentration: the muscarinic agonist
      carbachol, thapsigargin, and ionomycin. Time course studies revealed that Ca2+
      release from intracellular stores by carbachol produced an early rapid increase
      (0.25-0.5 min) in stimulated cAMP levels, whereas capacitative Ca2+ entry
      resulted in a sustained increase in stimulated cAMP levels that was blocked by
      La3+. Capacitative Ca2+ entry, alone, was involved in thapsigargin and ionomycin
      augmentation of stimulated cAMP accumulation. The inability of phosphodiesterase
      inhibitors, 3-isobutyl-1-methylxanthine and milrinone, to prevent agonist
      augmentation of cAMP levels, as well as the finding that the type VIII adenylyl
      cyclase (ACVIII) is expressed in parotid acini, suggests that capacitative Ca2+
      entry augments stimulated cAMP accumulation, at least in part, via activation of
      this adenylyl cyclase isoenzyme.

PMID- 9530087
TI  - A cationic nonselective stretch-activated channel in the Reissner's membrane of
      the guinea pig cochlea.
AB  - The Reissner's membrane (RM) separates in the mammalian cochlea the K(+)-rich
      endolymph from the Na(+)-rich perilymph. The patch-clamp technique was used to
      investigate the transport mechanisms in epithelial cells of RM freshly dissected
      from the guinea pig cochlea. This study shows a stretch-activated nonselective
      cationic channel (SA channel) with a linear current-voltage relationship (23 pS)
      highly selective for cations over anions [K+ approximately Na+ (1) > Ba2+ (0.65)
      > Ca2+ (0.32) >> Cl- (0.14)] and activated by the intrapipette gradient pressure.
      The open probability-pressure relationship is best fitted by a Boltzmann
      distribution (half-maximal pressure = 37.8 mmHg, slope constant = 8.2 mmHg). SA
      channels exhibit a strong voltage dependency and are insensitive to internal
      Ca2+, ATP, and fenamates but are blocked by 1 microM GdCl3 in the pipette. They
      are reversibly activated by in situ superfusion of the cell with hyposmotic
      solutions. Kinetic studies show that depolarization and mechanical or osmotic
      stretch modify the closed and open time constants probably by a different
      mechanism. These channels could participate in pressure-induced modifications of
      ionic permeability of the RM.

PMID- 9530088
TI  - Characterization of a transient outward K+ current with inward rectification in
      canine ventricular myocytes.
AB  - The threshold potential for the classical depolarization-activated transient
      outward K+ current and Cl- current is positive to -30 mV. With the whole cell
      patch technique, a transient outward current was elicited in the presence of 5 mM
      4-aminopyridine (4-AP) and 5 microM ryanodine at voltages positive to the K+
      equilibrium potential in canine ventricular myocytes. The current was abolished
      by 200 microM Ba2+ or omission of external K+ (K+o) and showed biexponential
      inactivation. The current-voltage relation for the peak of the transient outward
      component showed moderate inward rectification. The transient outward current
      demonstrated voltage-dependent inactivation (half-inactivation voltage: -43.5 +/-
      3.2 mV) and rapid, monoexponential recovery from inactivation (time constant:
      13.2 +/- 2.5 ms). The reversal potential responded to the changes in K+o
      concentration. Action potential clamp revealed two phases of Ba2(+)-sensitive
      current during the action potential, including a large early transient component
      after the upstroke and a later outward component during phase 3 repolarization.
      The present study demonstrates that depolarization may elicit a Ba2(+)- and K(+o)
      sensitive, 4-AP-insensitive, transient outward current with inward rectification
      in canine ventricular myocytes. The properties of this K+ current suggest that it
      may carry a significant early outward current upon depolarization that may play a
      role in determining membrane excitability and action potential morphology.

PMID- 9530089
TI  - Aldosterone stimulates intestinal Na+ absorption in rats by increasing NHE3
      expression of the proximal colon.
AB  - Na+ retention by the colon in response to salt deprivation is mediated in part by
      the resulting secondary hyperaldosteronism. We show that experimental
      hyperaldosteronism, to levels seen with salt deprivation, causes an increase in
      the selective expression and activity of NHE3, an apically located isoform of the
      Na+/H+ exchange family that functions in transepithelial Na+ absorption. The
      effect of aldosterone on NHE3 expression is tissue specific, occurring in
      intestine and not in kidney. Within the intestine, these effects are regional,
      being observed only in proximal colon, and different in distribution from that
      observed with glucocorticoids, where the predominant effect occurs in ileum.
      Although glucocorticoids are well known to exert many effects via regulation of
      transcript levels, the present study demonstrates that aldosterone stimulates
      intestinal Na+ absorption by increasing cellular NHE3 expression, a response that
      is tissue and region specific.

PMID- 9530090
TI  - Alpha-cardiac-like myosin heavy chain as an intermediate between MHCIIa and MHCI
      beta in transforming rabbit muscle.
AB  - To elucidate the sequence of myosin heavy chain (MHC) transitions in fast-to-slow
      transforming rabbit muscle, direct reverse transcriptase-polymerase chain
      reaction was applied for detecting mRNAs specific to five MHC isoforms in single
      fibers from control and low-frequency-stimulated tibialis anterior muscles. The
      detection of MHCIIb, MHCIId(x), MHCI alpha, and MHCI beta mRNAs was based on
      previously published methods. The RT-PCR assay for MHCIIa mRNA was based on the
      identification of a cDNA sequence in the 3'-region from which specific primers
      were derived. Comparisons between rat, rabbit, and human MHCIIa sequences
      revealed high degrees of sequence identities. MHC mRNA isoform patterns in single
      fibers from stimulated muscles showed hybrid fibers expressing the following
      combinations: MHCIId(x) + MHCIIa, MHCIId(x) + MHCIIa + MHCI alpha, MHCIId(x) +
      MHCIIa + MHCI alpha + MHCI beta, MHCIIa + MHCI alpha, MHCIIa + MHCI alpha + MHCI
      beta, and MHCI alpha + MHCI beta. The combination MHCIIa + MHCI beta without MHCI
      alpha was never seen. These coexpression patterns suggest that the fast-to-slow
      fiber transition results from sequential isoform expressions in the order
      MHCIId(x)--> MHCIIa-->MHCI alpha-->MHCI beta. The allocation of MHCI alpha
      between MHCIIa and MHCI beta seems to be in line with graded differences in
      sequence identity of the 3'-regions of these mRNA isoforms.

PMID- 9530091
TI  - Activity and protein localization of multiple glutamate transporters in gestation
      day 14 vs. day 20 rat placenta.
AB  - Concentrative absorption of glutamate by the developing placenta is critical for
      proper fetal development. The expression of GLAST1, GLT1, EAAC1, and EAAT4, known
      to be capable of D-aspartate-inhibitable and Na(+)-coupled glutamate transport
      (system X-AG), was evaluated in day 14 vs. day 20 rat chorioallantoic placenta.
      Steady-state mRNA levels were greater at day 20 for all transporters.
      Immunohistochemistry determined that the expression of GLAST1, GLT1, and EAAC1
      was greater throughout the day 20 placenta and was asymmetric with respect to
      cellular localization. EAAT4 protein was not detected. System X-AG activity was
      responsible for most of the Na(+)-dependent glutamate uptake and was greater in
      day 20 than in day 14 apical and basal membrane subdomains of the labyrinth
      syncytiotrophoblast. Greater quantities of EAAC1 and GLAST1 protein were
      identified on day 20, and quantities were greater in basal than in apical
      membranes. GLT1 expression, unchanged in apical membranes, was decreased in basal
      membranes. These data correlate transporter mRNA and protein content with
      transport activity and demonstrate an increasing capacity for glutamate
      absorption by the developing placenta.

PMID- 9530092
TI  - Reduced Ca2+ uptake by mitochondria in pyruvate dehydrogenase-deficient human
      diploid fibroblasts.
AB  - Physiological and pathological Ca2+ loads are thought to be taken up by
      mitochondria via a process dependent on aerobic metabolism. We sought to
      determine whether human diploid fibroblasts from a patient with an inherited
      defect in pyruvate dehydrogenase (PDH) exhibit a decreased ability to sequester
      cytosolic Ca2+ into mitochondria. Mobilization of Ca2+ stores with bradykinin
      (BK) increased the cytosolic Ca2+ concentration ([Ca2+]c) to comparable levels in
      control and PDH-deficient fibroblasts. In normal fibroblasts transfected with
      plasmid DNA encoding mitochondrion-targeted apoaequorin, BK elicited an increase
      in Ca2(+)-dependent aequorin luminescence corresponding to an increase in the
      mitochondrial Ca2+ concentration ([Ca2+]mt) of 2.0 +/- 0.2 microM. The
      mitochondrial uncoupling agent carbonyl cyanide p
      (trifluoromethoxy)phenylhydrazone blocked the BK-induced [Ca2+]mt increase,
      although it did not affect the [Ca2+]c transient. Basal [Ca2+]c and [Ca2+]mt in
      control and PDH-deficient cells were similar. However, confocal imaging of the
      potential-sensitive dye JC-1 indicated that the percentage of highly polarized
      mitochondria was reduced from 30 +/- 1% in normal cells to 19 +/- 2% in the PDH
      deficient fibroblasts. BK-elicited [Ca2+]mt transients in PDH-deficient cells
      were reduced to 4% of control, indicating that PDH-deficient mitochondria have a
      decreased ability to take up cytosolic Ca2+. Thus cells with compromised aerobic
      metabolism have a reduced capacity to sequester Ca2+.

PMID- 9530093
TI  - Imaging caffeine-induced Ca2+ transients in individual fast-twitch and slow
      twitch rat skeletal muscle fibers.
AB  - Fast-twitch and slow-twitch rat skeletal muscles produce dissimilar contractures
      with caffeine. We used digital imaging microscopy to monitor Ca2+ (with fluo 3
      acetoxymethyl ester) and sarcomere motion in intact, unrestrained rat muscle
      fibers to study this difference. Changes in Ca2+ in individual fibers were
      markedly different from average responses of a population. All fibers showed
      discrete, nonpropagated, local Ca2+ transients occurring randomly in spots about
      one sarcomere apart. Caffeine increased local Ca2+ transients and sarcomere
      motion initially at 4 mM in soleus and 8 mM in extensor digitorum longus (EDL;
      approximately 23 degrees C). Ca2+ release subsequently adapted or inactivated;
      this was surmounted by higher doses. Motion also adapted but was not surmounted.
      Prolonged exposure to caffeine evidently suppressed myofilament interaction in
      both types of fiber. In EDL fibers, 16 mM caffeine moderately increased local
      Ca2+ transients. In soleus fibers, 16 mM caffeine greatly increased Ca2+ release
      and produced propagated waves of Ca2+ (approximately 1.5-2.5 microns/s). Ca2+
      waves in slow-twitch fibers reflect the caffeine-sensitive mechanism of Ca2(+)
      induced Ca2+ release. Fast-twitch fibers possibly lack this mechanism, which
      could account for their lower sensitivity to caffeine.

PMID- 9530094
TI  - Cellular differentiation and I-FABP protein expression modulate fatty acid uptake
      and diffusion.
AB  - The effect of cellular differentiation on fatty acid uptake and intracellular
      diffusion was examined in transfected pluripotent mouse embryonic stem (ES) cells
      stably expressing intestinal fatty acid binding protein (I-FABP). Control ES
      cells, whether differentiated or undifferentiated, did not express I-FABP. The
      initial rate and maximal uptake of the fluorescent fatty acid, 12-(N-methyl)-N
      [(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-octadec anoic acid (NBD-stearic acid),
      was measured in single cells by kinetic digital fluorescence imaging. I-FABP
      expression in undifferentiated ES cells increased the initial rate and maximal
      uptake of NBD-stearic acid 1.7- and 1.6-fold, respectively, as well as increased
      its effective intracellular diffusion constant (Deff) 1.8-fold as measured by the
      fluorescence recovery after photobleaching technique. In contrast, ES cell
      differentiation decreased I-FABP expression up to 3-fold and decreased the NBD
      stearic acid initial rate of uptake, maximal uptake, and Deff by 10-, 4.7-, and 2
      fold, respectively. There were no significant differences in these parameters
      between the differentiated control and differentiated I-FABP-expressing ES cell
      lines. In summary, differentiation and expression of I-FABP oppositely modulated
      NBD-stearic acid uptake parameters and intracellular diffusion in ES cells.

PMID- 9530095
TI  - Cell-specific promoter in adenovirus vector for transgenic expression of SERCA1
      ATPase in cardiac myocytes.
AB  - Adenovirus-mediated transfer of cDNA encoding the chicken skeletal muscle
      sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA1) yielded selective expression
      in cultured chick embryo cardiac myocytes under control of a segment (-268 base
      pair) of the cell-specific cardiac troponin T (cTnT) promoter or nonselective
      expression in myocytes and fibroblasts under control of a constitutive viral
      [cytomegalovirus (CMV)] promoter. Under optimal conditions nearly all cardiac
      myocytes in culture were shown to express transgenic SERCA1 ATPase. Expression
      was targeted to intracellular membranes and was recovered in subcellular
      fractions with a pattern identical to that of the endogenous SERCA2a ATPase.
      Relative to control myocytes, transgenic SERCA1 expression increased up to four
      times the rates of ATP-dependent (and thapsigargin-sensitive) Ca2+ transport
      activity of cell homogenates. Although the CMV promoter was more active than the
      cTnT promoter, an upper limit for transgenic expression of functional enzyme was
      reached under control of either promoter by adjustment of the adenovirus plaque
      forming unit titer of infection media. Cytosolic Ca2+ concentration transients
      and tension development of whole myocytes were also influenced to a similar limit
      by transgenic expression of SERCA1 under control of either promoter. Our
      experiments demonstrate that a cell-specific protein promoter in recombinant
      adenovirus vectors yields highly efficient and selective transgene expression of
      a membrane-bound and functional enzyme in cardiac myocytes.

PMID- 9530096
TI  - Alpha 2-adrenergic receptors increase cell migration and decrease F-actin
      labeling in rat aortic smooth muscle cells.
AB  - Vascular wound healing and such pathologies as atherosclerosis and restenosis are
      characterized by migration and proliferation of the smooth muscle cells of the
      media after denudation of the intima. To explore possible roles that alpha 2
      adrenergic receptors (alpha 2-ARs) might have in these cellular responses, we
      characterized the alpha 2-ARs present in explant-derived cultures of rat aortic
      smooth muscle (RASM) cells. The results of immunofluorescence microscopy and
      reverse transcription followed by the polymerase chain reaction indicated that
      all three alpha 2-AR subtypes (alpha 2A, alpha 2B, and alpha 2C) were initially
      present. Mitogen-activated protein kinase activity in the RASM cells was
      stimulated fivefold over basal by the alpha 2-selective agonist dexmedetomidine
      (Dex) and was blocked by coincubation with the alpha 2-selective antagonist
      rauwolscine (RW) or by preincubation of the cells with the Gi/G(o)-protein
      inhibitor pertussis toxin. alpha 2-AR activation by Dex did not promote cell
      proliferation, as measured by the incorporation of [3H]thymidine. However, Dex
      significantly increased RASM cell migration, and antagonist blocked this effect.
      Incubation of RASM cells with Dex also produced a marked decrease in F-actin
      labeling, which again was prevented by coincubation with RW. The evidence clearly
      reveals the presence of functional alpha 2-ARs in RASM cells. The involvement of
      alpha 2-AR activation with cytoskeletal changes and cell migration is novel and
      indicates a potential role of these receptors in vascular wound healing and
      pathogenesis.

PMID- 9530098
TI  - Charybdotoxin block of Ca(2+)-activated K+ channels in colonic muscle depends on
      membrane potential dynamics.
AB  - Charybdotoxin (ChTX) is a specific blocker of Ca(2+)-activated K+ channels. The
      voltage- and time-dependent dynamics of ChTX block were investigated using canine
      colonic myocytes and the whole cell patch-clamp technique with step and ramp
      depolarization protocols. During prolonged step depolarizations, K+ current
      slowly increased in the continued presence of ChTX (100 nM). The rate of increase
      depended on membrane potential with an e-fold change for every 60 mV. During ramp
      depolarizations, the effectiveness of ChTX block depended significantly on the
      rate of the ramp (50% at 0.01 V/s to 80% at 0.5 V/s). Results are consistent with
      a mechanism in which ChTX slowly "unbinds" in a voltage-dependent manner. A
      simple kinetic model was developed in which ChTX binds to both open and closed
      states. Slow unbinding is consistent with ChTX having little effect on electrical
      slow waves recorded from circular muscle while causing depolarization and
      contraction of longitudinal muscle, which displays more rapid "spikes." Resting
      membrane potential and membrane potential dynamics are important determinants of
      ChTX action.

PMID- 9530097
TI  - Control of Ca2+ wave propagation in mouse pancreatic acinar cells.
AB  - We have investigated control mechanisms involved in the propagation of agonist
      induced Ca2+ waves in isolated mouse pancreatic acinar cells. Using a confocal
      laser-scanning microscope, we were able to show that maximal stimulation of cells
      with acetylcholine (ACh, 500 nM) or bombesin (1 nM) caused an initial Ca2+
      release of comparable amounts with both agonists at the luminal cell pole.
      Subsequent Ca2+ spreading to the basolateral membrane was faster with ACh (17.3
      +/- 5.4 microns/s) than with bombesin (8.0 +/- 2.2 microns/s). The speed of
      bombesin-induced Ca2+ waves could be increased up to the speed of ACh-induced
      Ca2+ waves by inhibition of protein kinase C (PKC). Activation of PKC
      significantly decreased the speed of ACh-induced Ca2+ waves but had only little
      effect on bombesin-evoked Ca2+ waves. Within 3 s after stimulation, production of
      inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] was higher in the presence of ACh
      compared with bombesin, whereas bombesin induced higher levels of diacylglycerol
      (DAG) than ACh. These data suggest that the slower propagation speed of bombesin
      induced Ca2+ waves is due to higher activation of PKC in the presence of bombesin
      compared with ACh. The higher increase in bombesin-compared with ACh-induced DAG
      production is probably due to activation of phospholipase D (PLD). Inhibition of
      the PLD-dependent DAG production by preincubation with 0.3% butanol led to an
      acceleration of the bombesin-induced Ca2+ wave. In further experiments, we could
      show that ruthenium red (100 microM), an inhibitor of Ca(2+)-induced Ca2+ release
      in skeletal muscle, also decreased the speed of ACh-induced Ca2+ waves. The
      effect of ruthenium red was not additive to the effect of PKC activation. From
      the data, we conclude that, following Ins(1,4,5)P3-induced Ca2+ release in the
      luminal cell pole, secondary Ca2+ release from stores, which are located in
      series between the luminal and the basal plasma membrane, modifies Ca2+ spreading
      toward the basolateral cell side by Ca(2+)-induced Ca2+ release. Activation of
      PKC leads to a reduction in Ca2+ release from these stores and therefore could
      explain the slower propagation of Ca2+ waves in the presence of bombesin compared
      with ACh.

PMID- 9530099
TI  - In vivo analysis of the myosin heavy chain IIB promoter region.
AB  - The myosin heavy chain (MHC) IIB gene is preferentially expressed in fast-twitch
      muscles of the hindlimb, such as the tibialis anterior (TA). The molecular
      mechanism(s) for this preferential expression are unknown. The goals of the
      current study were 1) to determine whether the cloned region of the MHC IIB
      promoter contains the necessary cis-acting element(s) to drive fiber-type
      specific expression of this gene in vivo, 2) to determine which region within the
      promoter is responsible for fiber-type-specific expression, and 3) to determine
      whether transcription off of the cloned region of the MHC IIB promoter accurately
      mimics endogenous gene expression in a muscle undergoing a fiber-type transition.
      To accomplish these goals, a 2.6-kilobase fragment of the promoter-enhancer
      region of the MHC IIB gene was cloned upstream of the firefly luciferase reporter
      gene and coinjected with pRL-cytomegalovirus (CMV) (CMV promoter driving the
      renilla luciferase reporter) into the TA and the slow soleus muscle. Firefly
      luciferase activity relative to renilla luciferase activity within the TA was 35
      fold greater than within the soleus. Deletional analysis demonstrated that only
      the proximal 295 base pairs (pGL3IIB0.3) were required to maintain this muscle
      fiber-type specificity. Reporter gene expression of pGL3IIB0.3 construct was
      significantly upregulated twofold in unweighted soleus muscles compared with
      normal soleus muscles. Thus the region within the proximal 295 base pairs of the
      MHC IIB gene contains at least one element that can drive fiber-type-specific
      expression of a reporter gene.

PMID- 9530100
TI  - A basolateral sorting signal is encoded in the alpha-subunit of Na-K-ATPase.
AB  - Na-K-ATPase and H-K-ATPase are highly homologous ion pumps that exhibit distinct
      plasma membrane distributions in epithelial cells. We have studied the alpha
      subunits of these heterodimeric pumps to identify the protein domains responsible
      for their polarized sorting. A chimeric alpha-subunit construct (N519H) was
      generated in which the first 519 amino acid residues correspond to the Na-K
      ATPase sequence and the remaining 500 amino acids are derived from the H-K-ATPase
      sequence. In stably transfected LLC-PK1 cell lines, we found that the N519H
      chimera is restricted to the basolateral surface under steady-state conditions,
      suggesting that residues within the NH2-terminal 519 amino acids of the Na-K
      ATPase alpha-subunit contain a basolateral sorting signal. H-K-ATPase beta
      subunit expressed alone in LLC-PK1 cells accumulates at the apical surface. When
      coexpressed with N519H, the H-K-ATPase beta-subunit assembles with this chimera
      and accompanies it to the basolateral surface. Thus the NH2-terminal basolateral
      signal in the Na-K-ATPase alpha-subunit masks or is dominant over any apical
      sorting information present in the beta-polypeptide. In gastric parietal cells,
      the H-K-ATPase beta-subunit targets the H-K-ATPase to an intracellular vesicular
      compartment which fuses with the plasma membrane in response to secretagogue
      stimulation. To test whether the chimera-H-K-ATPase beta-subunit complex is
      directed to a similar compartment in LLC-PK1 cells, we treated transfected cells
      with drugs that raise intracellular adenosine 3',5'-cyclic monophosphate (cAMP)
      levels. Elevation of cytosolic cAMP increased the surface expression of both the
      N519H chimera and the H-K-ATPase beta-subunit. This increase in surface
      expression, however, appears to be the result of transcriptional upregulation and
      not recruitment of chimera to the surface from a cAMP-inducible compartment.

PMID- 9530101
TI  - Osmotic regulation of intestinal epithelial Na(+)-K(+)-Cl- cotransport: role of
      Cl- and F-actin.
AB  - Previous data indicate that adenosine 3',5'-cyclic monophosphate activates the
      epithelial basolateral Na(+)-K(+)-Cl- cotransporter in microfilament-dependent
      fashion in part by direct action but also in response to apical Cl- loss (due to
      cell shrinkage or decreased intracellular Cl-). To further address the actin
      dependence of Na(+)-K(+)-Cl- cotransport, human epithelial T84 monolayers were
      exposed to anisotonicity, and isotopic flux analysis was performed. Na(+)-K(+)-Cl
      cotransport was activated by hypertonicity induced by added mannitol but not
      added NaCl. Cotransport was also markedly activated by hypotonic stress, a
      response that appeared to be due in part to reduction of extracellular Cl-
      concentration and also to activation of K+ and Cl- efflux pathways. Stabilization
      of actin with phalloidin blunted cotransporter activation by hypotonicity and
      abolished hypotonic activation of K+ and Cl- efflux. However, phalloidin did not
      prevent activation of cotransport by hypertonicity or isosmotic reduction of
      extracellular Cl-. Conversely, hypertonic but not hypotonic activation was
      attenuated by the microfilament disassembler cytochalasin D. The results
      emphasize the complex interrelationship among intracellular Cl- activity, cell
      volume, and the actin cytoskeleton in the regulation of epithelial Cl- transport.

PMID- 9530102
TI  - Human orbital fibroblasts are activated through CD40 to induce proinflammatory
      cytokine production.
AB  - CD40 is an important signaling and activation antigen found on certain bone
      marrow-derived cells. Recently, CD40 has also been shown to be expressed by
      nonhematopoietic cells, including certain human fibroblasts, but not others.
      Little is known about the function of CD40 on fibroblasts. The current study
      investigates the hypothesis that CD40 is expressed on orbital fibroblasts and
      represents a pathway for interaction between these fibroblasts and CD40 ligand
      expressing cells, such as T lymphocytes and mast cells. We report here that
      orbital connective tissue fibroblasts, obtained from normal donors and from
      patients with severe thyroid-associated ophthalmopathy (TAO), express functional
      CD40. CD40 is upregulated approximately 10-fold by interferon-gamma (500 U/ml)
      treatment for 72 h. These fibroblasts become activated through triggering of CD40
      with CD40 ligand (CD40L). This is evidenced by nuclear translocation of nuclear
      factor-kappa B and induction of the proinflammatory and chemoattractant cytokines
      interleukin-6 and interleukin-8, respectively. These data support the concept
      that cognate interactions between orbital fibroblasts and infiltrating T
      lymphocytes, via the CD40-CD40L pathway, may promote the tissue remodeling
      observed in TAO and other inflammatory diseases of the orbit. Disruption of the
      CD40-CD40L interaction may represent a therapeutic intervention to reduce the
      inflammatory components of TAO, which remains a vexing clinical problem.

PMID- 9530103
TI  - A divergent CFTR homologue: highly regulated salt transport in the euryhaline
      teleost F. heteroclitus.
AB  - The killifish, Fundulus heteroclitus, is a euryhaline teleost fish capable of
      adapting rapidly to transfer from freshwater (FW) to four times seawater (SW). To
      investigate osmoregulation at a molecular level, a 5.7-kilobase cDNA homologous
      to human cystic fibrosis transmembrane conductance regulator (hCFTR) was isolated
      from a gill cDNA library from SW-adapted killifish. This cDNA encodes a protein
      product (kfCFTR) that is 59% identical to hCFTR, the most divergent form of CFTR
      characterized to date. Expression of kfCFTR in Xenopus oocytes generated
      adenosine 3',5'-cyclic monophosphate-activated, Cl(-)-selective currents similar
      to those generated by hCFTR. In SW-adapted killifish, kfCFTR was expressed at
      high levels in the gill, opercular epithelium, and intestine. After abrupt
      exposure of FW-adapted killifish to SW, kfCFTR expression in the gill increased
      severalfold, suggesting a role for kfCFTR in salinity adaptation. Under similar
      conditions, plasma Na+ levels rose significantly after 8 h and then fell,
      although it is not known whether these changes are directly responsible for the
      changes in kfCFTR expression. The killifish provides a unique opportunity to
      understand teleost osmoregulation and the role of CFTR.

PMID- 9530104
TI  - ATP stimulation of Na+/Ca2+ exchange in cardiac sarcolemmal vesicles.
AB  - In cardiac sarcolemmal vesicles, MgATP stimulates Na+/Ca2+ exchange with the
      following characteristics: 1) increases 10-fold the apparent affinity for
      cytosolic Ca2+; 2) a Michaelis constant for ATP of approximately 500 microM; 3)
      requires micromolar vanadate while millimolar concentrations are inhibitory; 4)
      not observed in the presence of 20 microM eosin alone but reinstated when
      vanadate is added; 5) mimicked by adenosine 5'-O-(3-thiotriphosphate), without
      the need for vanadate, but not by beta,gamma-methyleneadenosine 5'-triphosphate;
      and 6) not affected by unspecific protein alkaline phosphatase but abolished by a
      phosphatidylinositol-specific phospholipase C (PI-PLC). The PI-PLC effect is
      counteracted by phosphatidylinositol. In addition, in the absence of ATP, L-alpha
      phosphatidylinositol 4,5-bisphosphate (PIP2) was able to stimulate the exchanger
      activity in vesicles pretreated with PI-PLC. This MgATP stimulation is not
      related to phosphorylation of the carrier, whereas phosphorylation appeared in
      the phosphoinositides, mainly PIP2, that coimmunoprecipitate with the exchanger.
      Vesicles incubated with MgATP and no Ca2+ show a marked synthesis of L-alpha
      phosphatidylinositol 4-monophosphate (PIP) with little production of PIP2; in the
      presence of 1 microM Ca2+, the net synthesis of PIP is smaller, whereas that of
      PIP2 increases ninefold. These results indicate that PIP2 is involved in the
      MgATP stimulation of the cardiac Na+/Ca2+ exchanger through a fast
      phosphorylation chain: a Ca(2+)-independent PIP formation followed by a Ca(2+)
      dependent synthesis of PIP2.

PMID- 9530105
TI  - Basic fibroblast growth factor destabilizes osteonectin mRNA in osteoblasts.
AB  - Osteonectin (secreted protein acidic and rich in cysteine, 40-kDa basement
      membrane) is a glycoprotein abundantly expressed in bone and in other tissues
      undergoing active remodeling. Fibroblast growth factors (FGFs) are important in
      skeletal development and fracture repair, events associated with extracellular
      matrix remodeling. We used the murine osteoblastic cell line MC3T3 to determine
      whether basic FGF (bFGF) regulates osteonectin expression in bone. Northern blot
      analysis showed that bFGF decreased osteonectin transcripts in a dose- and time
      dependent manner. This regulation was independent of the mitogenic effect of bFGF
      but was dependent on new protein synthesis. Immunoprecipitation of
      [35S]methionine-cysteine osteoblast-conditioned medium and cell layer proteins
      showed that bFGF decreased osteonectin synthesis. Nuclear runoff assays failed to
      reveal regulation of osteonectin gene transcription by bFGF. However, bFGF
      dramatically decreased the stability of osteonectin mRNA in transcriptionally
      arrested osteoblasts. This destabilization of osteonectin mRNA may be one means
      by which bFGF regulates extracellular matrix remodeling.

PMID- 9530106
TI  - Relationship between paxillin and myosin phosphorylation during muscarinic
      stimulation of smooth muscle.
AB  - The tyrosine phosphorylation of paxillin increases in association with force
      development during tracheal smooth muscle contraction, suggesting that paxillin
      plays a role in the contractile activation of smooth muscle [Z. L. Wang, F. M.
      Pavalko, and S. J. Gunst. Am. J. Physiol. 271 (Cell Physiol. 40): C1594-C1602,
      1996]. We compared the Ca2+ sensitivity of the tyrosine phosphorylation of
      paxillin and myosin light chain (MLC) phosphorylation in tracheal muscle and
      evaluated whether MLC phosphorylation is necessary to induce paxillin
      phosphorylation. Ca(2+)-depleted muscle strips were stimulated with 10(-7)-10(-4)
      M acetylcholine (ACh) in 0,0.05, 0.1, or 0.5 mM extracellular Ca2+. In the
      absence of extracellular Ca2+, 10(-4) M ACh induced a maximal increase in
      paxillin phosphorylation without increasing MLC phosphorylation or force.
      Increases in extracellular Ca2+ concentration did not further increase paxillin
      phosphorylation. However, during stimulation with 10(-6) M ACh, paxillin
      phosphorylation increased with increases in extracellular Ca2+ concentration. We
      conclude that the tyrosine phosphorylation of paxillin can be stimulated by
      signaling pathways that do not depend on Ca2+ mobilization and that the
      activation of contractile proteins is not required to elicit paxillin
      phosphorylation.

PMID- 9530107
TI  - Regulation of cGMP-induced relaxation and cGMP-dependent protein kinase in rat
      myometrium during pregnancy.
AB  - Increases in guanosine 3',5'-cyclic monophosphate (cGMP) induced by nitric oxide
      (NO), nitrovasodilators, and atrial peptides correlate with relaxation of
      vascular smooth muscle. Relaxation of myometrial smooth muscle by increases in
      cGMP, however, has required unusually high concentrations of the cyclic
      nucleotide. We tested the hypothesis that the sensitivity of myometrium to
      relaxation by cGMP is increased during pregnancy. Aortic smooth muscle was more
      sensitive to relaxation by cGMP than myometrial tissues, and, contrary to our
      hypothesis, myometrium from pregnant rats was least sensitive. Although levels of
      cGMP were elevated after treatment with the NO donor, S-nitroso-N
      acetylpenicillamine, relaxation of myometrial tissues obtained from pregnant rats
      occurred only at extraordinarily high concentrations. The levels of cGMP
      dependent protein kinase (PKG) were significantly decreased in myometrium from
      pregnant rats compared with myometrium from nonpregnant cycling animals or aortic
      smooth muscle. Administration of estradiol to ovariectomized rats increased
      myometrial PKG expression, and progesterone antagonized this response. We
      conclude that 1) myometrial tissues from pregnant rats are not sensitive to
      relaxation by cGMP and 2) this insensitivity to cGMP is accompanied by
      progesterone-mediated decreases in the level of PKG expression.

PMID- 9530108
TI  - Phosphate transport by the human renal cotransporter NaPi-3 expressed in HEK-293
      cells.
AB  - The human renal Na-PO4 cotransporter gene NaPi-3 was expressed in human embryonic
      kidney HEK-293 cells, and the transport characteristics were measured in cells
      transfected with a vector containing NaPi-3 or with the vector alone (sham
      transfected). The initial rate of 32PO4 influx had saturation kinetics for
      external Na and PO4 with K1/2Na of 128 mM (PO4 = 0.1 mM) and K1/2PO4 of 0.084 mM
      (extracellular Na = 143 mM) in sham- and NaPi-3-transfected cells expressing the
      transporter. Transfection had no effect on the Na-independent 32PO4 influx, but
      transfection increased Na-dependent 32PO4 influxes 2.5- to 5-fold. Of the alkali
      cations, only Na significantly supported PO4 influx. Arsenate inhibited flux with
      an inhibition constant of 0.4 mM. The phosphate transport in sham- and NaPi-3
      transfected cells has nearly the same temperature dependence in the absence and
      presence of extracellular Na. The Na-dependent phosphate flux decreased with pH
      in sham-transfected cells but was pH independent in transfected cells. The Na
      dependent 32PO4 influx was inhibited by p-chloromercuriphenylsulfonate,
      phosphonoformate, phloretin, vanadate, and 5-(N-methyl-N-isobutyl)-amiloride but
      not by amiloride or other amiloride analogs. These functional characteristics are
      in general agreement with the known behavior of NaPi-3 homologues in the renal
      tubule of other species and, thus, demonstrate the fidelity of this transfection
      system for the study of this protein. Commensurate with the increased functional
      expression, there was an increase in the amount of NaPi-3 protein by Western
      analysis.

PMID- 9530109
TI  - Endotoxin-induced skeletal muscle contractile dysfunction: contribution of nitric
      oxide synthases.
AB  - The aims of this study were to assess the role of nitric oxide (NO) and the
      contribution of different NO synthase (NOS) isoforms in skeletal muscle
      contractile dysfunction in septic shock. Four groups of conscious rats were
      examined. Group 1 served as control; group 2, 3, and 4 were injected with
      Escherichia coli endotoxin [lipopolysaccharide (LPS), 20 mg/kg i.p.] and killed
      after 6, 12, and 24 h, respectively. Protein expression was assessed by
      immunoblotting and immunostaining. LPS injection elicited a transient expression
      of the inducible NOS isoform, which peaked 12 h after LPS injection and
      disappeared within 24 h. This expression coincided with a significant increase in
      nitrotyrosine formation (peroxynitrite foot-print). Muscle expression of the
      endothelial and neuronal NOS isoforms, by comparison, rose significantly and
      remained higher than control levels 24 h after LPS injection. In vitro
      measurement of muscle contractility 24 h after LPS injection showed that
      incubation with NOS inhibitor (S-methyliosothiourea) restored the decline in
      submaximal force generation, whereas maximal muscle force remained unaffected. We
      conclude that NO plays a significant role in muscle contractile dysfunction in
      septic animals and that increased NO production is due to induction of the
      inducible NOS isoform and upregulation of constitutive NOS isoforms.

PMID- 9530111
TI  - Activation of p42mapk in human umbilical vein endothelial cells by interleukin-1
      alpha and tumor necrosis factor-alpha.
AB  - Work from this and other laboratories has identified a role for protein tyrosine
      kinases in interleukin-1 alpha (IL-1 alpha)- and tumor necrosis factor-alpha (TNF
      alpha)-induced responses in endothelial cells. In this study, we show that
      activation of human umbilical vein endothelial cells (HUVEC) by IL-1 alpha leads
      to increased tyrosine phosphorylation of several proteins including one with a
      molecular mass of approximately 42 kDa. This protein was identified as p42mapk by
      Western blot analysis. Tyrosine phosphorylation and catalytic activation of
      p42mapk by IL-1 alpha was transient, reaching maximal levels after 30 min and
      returning to basal levels by 120-300 min. Activation of p42mapk in HUVEC was also
      observed in response to TNF-alpha or to the protein kinase C (PKC)-activating
      phorbol ester phorbol 12-myristate 13-acetate (PMA). Pretreatment of HUVEC with
      IL-1 alpha or TNF-alpha prevented reactivation of p42mapk by either cytokine but
      did not affect subsequent activation in response to PMA. Activation of p42mapk by
      PMA was significantly reduced by the PKC inhibitor Ro-31-8220 and completely
      inhibited by the protein tyrosine kinase inhibitor genistein. Genistein, but not
      Ro-31-8220, attenuated IL-1 alpha- and TNF-alpha-induced p42mapk activation.
      Taken together, the results of this study demonstrate 1) that p42mapk is
      transiently activated in HUVEC by IL-1 alpha and TNF-alpha, 2) that this
      activation is PKC independent, and 3) that a genistein-inhibitable tyrosine
      kinase may be an upstream regulator of cytokine-induced p42mapk activation in
      human endothelium.

PMID- 9530110
TI  - Ontogeny of malate-aspartate shuttle capacity and gene expression in cardiac
      mitochondria.
AB  - Developmental downregulation of the malate-aspartate shuttle has been observed in
      cardiac mitochondria. The goals of this study were to determine the time course
      of the postnatal decline and to identify potential regulatory sites by measuring
      steady-state myocardial mRNA and protein levels of the mitochondrial proteins
      involved in the shuttle. By use of isolated porcine cardiac mitochondria
      incubated with saturating concentrations of the cytosolic components of the
      malate-aspartate shuttle, shuttle capacity was found to decline by approximately
      50% during the first 5 wk of life (from 921 +/- 48 to 531 +/- 53 nmol.min-1.mg
      protein-1). Mitochondrial aspartate aminotransferase mRNA levels were greater in
      adult than in newborn myocardium. mRNA levels of mitochondrial malate
      dehydrogenase in adult cardiac tissue were 224% of levels in newborn tissue,
      whereas protein levels were 54% greater in adult myocardium. Aspartate/glutamate
      carrier protein levels were also greater in adult than in newborn tissue. mRNA
      and protein levels of the oxoglutarate/malate carrier were increased in newborn
      myocardium. It was concluded that 1) myocardial malate-aspartate shuttle capacity
      declines rapidly after birth, 2) divergence of mitochondrial malate dehydrogenase
      mRNA and protein levels during development suggests posttranscriptional
      regulation of this protein, and 3) the developmental decline in malate-aspartate
      shuttle capacity is regulated by decreased oxoglutarate/malate carrier gene
      expression.

PMID- 9530112
TI  - Electrodiffusional ATP movement through the cystic fibrosis transmembrane
      conductance regulator.
AB  - Expression of the cystic fibrosis transmembrane conductance regulator (CFTR), and
      of at least one other member of the ATP-binding cassette family of transport
      proteins, P-glycoprotein, is associated with the electrodiffusional movement of
      the nucleotide ATP. Evidence directly implicating CFTR expression with ATP
      channel activity, however, is still missing. Here it is reported that
      reconstitution into a lipid bilayer of highly purified CFTR of human epithelial
      origin enables the permeation of both Cl- and ATP. Similar to previously reported
      data for in vivo ATP current of CFTR-expressing cells, the reconstituted channels
      displayed competition between Cl- and ATP and had multiple conductance states in
      the presence of Cl- and ATP. Purified CFTR-mediated ATP currents were activated
      by protein kinase A and ATP (1 mM) from the "intracellular" side of the molecule
      and were inhibited by diphenylamine-2-carboxylate, glibenclamide, and anti-CFTR
      antibodies. The absence of CFTR-mediated electrodiffusional ATP movement may thus
      be a relevant component of the pleiotropic cystic fibrosis phenotype.

PMID- 9530113
TI  - Sequential increases in capillarization and mitochondrial enzymes in low
      frequency-stimulated rabbit muscle.
AB  - To investigate temporal changes in capillarization and increases in mitochondrial
      enzyme activity, rabbit tibialis anterior muscles underwent chronic low-frequency
      stimulation for up to 50 days. Capillary density (CD), capillary-to-fiber ratio
      (C/F), intercapillary distance (ICD), and mean capillary area (MCA), as well as
      several other parameters of capillarization, were examined. In addition, tissue
      levels of mRNA specific to vascular endothelial growth factor (VEGF) were
      assessed by reverse transcriptase-polymerase chain reaction. Citrate synthase
      (CS) activity, a marker of aerobic-oxidative metabolic potential, was measured in
      the same muscles. Significant increases in CD and C/F, respectively, and
      decreases in ICD and MCA were observed after 2 days. These changes reached stable
      maxima by 14 days. The increases in capillarization occurred in a fiber-type
      specific manner, affecting type IId fibers before types IIda and IIa. VEGF mRNA
      levels increased in a bimodal time pattern with a first elevation (2.5-fold)
      after 1 day and a second (9-fold) after 6-8 days. Increases in CS were first
      noted after 8 days. Obviously, increases in capillarization as induced by
      enhanced contractile activity precede increases in the aerobic-oxidative
      potential of energy metabolism.

PMID- 9530114
TI  - Type II protein kinase A regulates CFTR in airway, pancreatic, and intestinal
      cells.
AB  - The type of protein kinase A (PKA) responsible for cystic fibrosis transmembrane
      conductance regulator (CFTR) activation was determined with adenosine 3', 5'
      cyclic monophosphate analogs capable of selectively activating type I or type II
      PKA. The type II-selective pair stimulated chloride efflux in airway, pancreatic,
      and colonic epithelial cells; the type I-selective pair only stimulated a calcium
      dependent efflux in airway cells. The type II-selective analogs activated larger
      increases in CFTR-mediated current than did the type I-selective analogs.
      Measurement of soluble PKA activity demonstrated similar levels stimulated by
      type I- and type II-selective analogs, creating an apparent paradox regarding PKA
      activity and current generated. Also, addition of forskolin after the type I
      selective analogs resulted in an increase in current; little increase was seen
      after the type II-selective analogs. Measurement of insoluble PKA activity
      stimulated by the analogs resolved this paradox. Type II-selective analogs
      stimulated three times as much insoluble PKA activity as the type I-selective
      pair, indicating that differential activation of PKA in cellular compartments is
      important in CFTR regulation.

PMID- 9530115
TI  - Nitric oxide inhibits superoxide production by inflammatory polymorphonuclear
      leukocytes.
AB  - Nitric oxide (NO.) has a complex role in the inflammatory response. In this
      study, we modified the levels of endogenous NO. in vivo in an acute model of
      inflammation and evaluated the interactions between NO. and superoxide anion (O2
      .) produced by polymorphonuclear leukocytes (PMNs) accumulated in the inflamed
      area. We injected phosphate-buffered saline (control group), 6 mumol of L-N5-(1
      iminoethyl)ornithine (L-NIO group), or 6 mumol of L-arginine (L-arginine group)
      into the granuloma pouch induced by carrageenan in rats. NO2- plus NO3-
      (indicative of NO. generation) was 188 nmol in the exudate of the control group,
      but it decreased in the L-NIO group (P < 0.05) and increased in the L-arginine
      group (P < 0.05). When PMNs from treated rats were incubated in vitro, the
      production of superoxide anion (O2-.) decreased by approximately 46% in the L
      arginine group. Furthermore, O2-. was inhibited in PMNs when L-arginine was added
      to the incubation medium before phorbol 12-myristate 13-acetate stimulation but
      not when added simultaneously. Our results suggest a protective role for NO. in
      inflammation, through the inactivation of NADPH oxidase and the consequent
      impairment of O2-. production for cell-mediated injury.

PMID- 9530117
TI  - Capillary electrophoretic measurement of tissue metabolites.
AB  - A method for the measurement of tissue metabolites from rabbit urinary bladder
      using capillary electrophoresis (CE) has been developed. The method generates a
      reproducible electropherogram containing > 20 peaks, including NAD, NADH,
      lactate, UDP-glucose, phosphocreatine, creatine, ATP, ADP, GTP, and UTP, from <
      20 nl of extract solution generated from 1.1 nl (or approximately 1.2 micrograms)
      of tissue in < 40 min. Multiple samples from the same bladder produce SE
      comparable with enzymatic or nuclear magnetic resonance (NMR) measurements of
      metabolites: phosphorus-NMR measurement requires 10(6) more tissue than CE;
      individual enzymatic measurements using 100 microliters/sample require 2,000
      microliters, a 10(5) greater volume than required by CE for the same number of
      metabolites. CE detects about three times more peaks than phosphorus-NMR on a
      similar time scale. Comparable measurements using enzymatic analysis would
      require approximately 10 times longer. The combination of minimal tissue volume
      requirements, rapid measurement, and reproducibility makes CE a valuable tool in
      the investigation of simultaneous changes in multiple metabolites from minute
      tissue samples.

PMID- 9530116
TI  - Regulation of Na+/H+ exchanger gene expression: mitogenic stimulation increases
      NHE1 promoter activity.
AB  - We examined factors important in regulation of expression of the Na+/H+ exchanger
      gene in NIH/3T3 cells. A stable fibroblast cell line was generated that contained
      a 1.1-kb proximal fragment of the mouse NHE1 promoter. The addition of serum to
      serum-starved cells resulted in an increase in activity of the NHE1 promoter. The
      mitogenic agonists insulin, thrombin, and epidermal growth factor also increased
      transcription from the NHE1 promoter. Phorbol esters also increased NHE1 promoter
      directed transcription, whereas the serine/threonine protein kinase inhibitor 1
      (5-isoquinolinylsulfonyl)-2-methylpiperazine inhibited this stimulation. The
      protein kinase inhibitors GF-109203X, PD-98059, and genistein all stimulated
      promoter activity. Promoter deletion analysis and gel mobility shift assays
      showed that a region between 0.9 and 1.1 kb from the start site was involved in
      mediating the effect of mitogenic stimulation. The results show that a variety of
      mitogenic factors can activate the NHE1 promoter during cell growth and
      proliferation.

PMID- 9530118
TI  - Metabolic fluctuation during a muscle contraction cycle.
AB  - Gated 31P-nuclear magnetic resonance followed the metabolic fluctuation in rat
      gastrocnemius muscle during a contraction cycle. Within 16 ms after stimulation,
      the phosphocreatine (PCr) level drops 11.3% from its reference state. The PCr
      minimum corresponds closely to the time of maximum force contraction. Pi
      increases stoichiometrically, while ATP remains constant. During a twitch, PCr
      hydrolysis produces 3.1 mumol ATP/g tissue, which is substantially higher than
      the reported 0.3 mumol ATP.twitch-1.g tissue-1 derived from steady-state
      experiments. The results reveal that a substantial energy fluctuation accompanies
      a muscle twitch.

PMID- 9530120
TI  - Contraction duration affects metabolic energy cost and fatigue in skeletal
      muscle.
AB  - It has been suggested that during a skeletal muscle contraction the metabolic
      energy cost at the onset may be greater than the energy cost related to holding
      steady-state force. The purpose of the present study was to investigate the
      effect of contraction duration on the metabolic energy cost and fatigue process
      in fully perfused contracting muscle in situ. Canine gastrocnemius muscle (n = 6)
      was isolated, and two contractile periods (3 min of isometric, tetanic
      contractions with 45-min rest between) were conducted by each muscle in a
      balanced order design. The two contractile periods had stimulation patterns that
      resulted in a 1:3 contraction-to-rest ratio, with the difference in the two
      contractile periods being in the duration of each contraction: short duration
      0.25-s stimulation/0.75-s rest vs. long duration 1-s stimulation/3-s rest. These
      stimulation patterns resulted in the same total time of stimulation, number of
      stimulation pulses, and total time in contraction for each 3-min period. Muscle
      O2 uptake, the fall in developed force (fatigue), the O2 cost of developed force,
      and the estimated total energy cost (ATP utilization) of developed force were
      significantly greater (P < 0.05) with contractions of short duration. Lactate
      efflux from the working muscle and muscle lactate concentration were
      significantly greater with contractions of short duration, such that the
      calculated energy derived from glycolysis was three times greater in this
      condition. These results demonstrate that contraction duration can significantly
      affect both the aerobic and anaerobic metabolic energy cost and fatigue in
      contracting muscle. In addition, it is likely that the greater rate of fatigue
      with more rapid contractions was a result of elevated glycolytic production of
      lactic acid.

PMID- 9530119
TI  - Cortisol infusion depresses the ratio of bioactive to immunoreactive ACTH in
      adrenalectomized sheep fetuses.
AB  - We examined the effects of exogenous cortisol on plasma immunoreactive
      adrenocorticotropic hormone (iACTH), bioactive ACTH (bACTH), and ACTH-(1-39) in
      nine adrenalectomized fetuses at 126-130 and 136-140 days of gestation. Fetuses
      received 4 h of cortisol (2 micrograms.kg-1.min-1) or saline infusions on
      consecutive days. Blood was obtained before and at intervals during infusions.
      Arterial blood gases and hematocrits were normal and did not change with age.
      Plasma cortisol did not change during saline infusions but increased
      significantly (range 30-70 ng/ml) during cortisol infusions. Basal plasma iACTH,
      bACTH, ACTH-(1-39), and bACTH-to-iACTH and ACTH-(1-39)-to-iACTH ratios were
      significantly higher in the older fetuses. Cortisol infusions decreased plasma
      iACTH, bACTH, and ACTH-(1-39) in both groups, and the suppression as a percent of
      the baseline was similar. The bACTH-to-iACTH ratio declined to the same level at
      126-130 (0.201 +/- 0.040 to 0.051 +/- 0.002) and 136-140 (0.389 +/- 0.088 to
      0.046 +/- 0.002) days of gestation. These data suggest that physiological
      concentrations of cortisol selectively inhibit bACTH secretion, and the ACTH
      response to cortisol inhibition is not different between 126 and 140 days of
      gestation in adrenalectomized sheep fetuses.

PMID- 9530121
TI  - Insulin sensitivity is associated with blood pressure response to sodium in older
      hypertensives.
AB  - The purpose of this study was to determine whether sodium-resistant hypertensives
      are more insulin resistant and whether dietary sodium restriction improves
      insulin sensitivity in older hypertensives. Insulin sensitivity was assessed by a
      frequently sampled intravenous glucose tolerance test to determine the insulin
      sensitivity index (SI) after 1 wk each of low- (20 mmol.l-1.day-1) and high- (200
      mmol.l-1.day-1) sodium diets in 21 older (63 +/- 2 yr) hypertensives. Subjects
      were grouped on the difference in mean arterial blood pressure (MABP) between
      diets [sodium sensitive (SS): > or = 5-mmHg increase in MABP on the high-sodium
      diet (n = 14); sodium resistant (SR): < 5-mmHg increase in MABP on the high
      sodium diet (n = 7)]. There was no dietary sodium effect on fasting plasma
      insulin or SI. An analysis of variance indicated a significant (P = 0.0002) group
      effect, with SS individuals having lower fasting plasma insulins on the low- (13
      +/- 2 vs. 27 +/- 3 microU/ml) and high- (12 +/- 2 vs. 22 +/- 3 microU/ml) sodium
      diets compared with SR individuals. Similarly, there was a significant (P =
      0.0002) group effect in regard to SI, with SS individuals having significantly
      higher SI on the low- (3.26 +/- 0.60 vs. 0.91 +/- 0.31 microU x 10(-4).min-1.ml
      1) and high- (3.45 +/- 0.51 vs. 1.01 +/- 0.30 microU x 10(-4).min-1.ml-1) sodium
      diets compared with SR individuals. We conclude that SR individuals exhibit a
      greater degree of insulin resistance than SS individuals and that dietary sodium
      restriction fails to improve insulin sensitivity regardless of sodium sensitivity
      status.

PMID- 9530123
TI  - Divergent changes in plasma ACTH and pituitary POMC mRNA after cortisol
      administration to late-gestation ovine fetus.
AB  - Plasma concentrations of cortisol and adrenocorticotropic hormone (ACTH) rise in
      the late-gestation sheep fetus at approximately the same time as there is an
      increase in the plasma levels of corticosteroid-binding globulin (CBG). We
      hypothesized that intrafetal cortisol infusion during late pregnancy would
      stimulate an increase in fetal plasma CBG, which in turn would bind cortisol and
      diminish glucocorticoid negative-feedback regulation of the fetal pituitary,
      leading to an increase in plasma ACTH concentrations. Cortisol was infused into
      chronically catheterized fetal sheep beginning at 126.1 +/- 0.5 days of gestation
      and continued for 96 h. Control fetuses were infused with saline. In cortisol
      infused fetuses, the plasma cortisol concentrations rose significantly from
      control levels (4.4 +/- 0.6 ng/ml) to 19.3 +/- 3.1 ng/ml within 24 h and remained
      significantly elevated throughout the infusion period. Plasma immunoreactive
      (i.r.) ACTH concentrations were significantly elevated in cortisol-infused
      fetuses within 24-48 h and remained significantly higher than in controls
      throughout the 96-h experimental period. Plasma free cortisol concentrations
      increased 10-fold and remained significantly elevated in cortisol-infused
      animals, despite a rise in plasma corticosteroid-binding capacity. Levels of
      pituitary proopiomelanocortin (POMC) mRNA in the fetal pars distalis and pars
      intermedia were 96 and 38% lower, respectively, after 96 h of cortisol infusion.
      Therefore physiological elevations of plasma cortisol, in the late-gestation
      ovine fetus, lead to increases in mean plasma irACTH concentrations, but this is
      not associated with increases in fetal pituitary POMC mRNA levels.

PMID- 9530122
TI  - Food restriction alters pregnancy-associated changes in IGF and IGFBP in the
      guinea pig.
AB  - The effect of moderate food restriction on pregnancy-associated changes in weight
      gain, body composition, and circulating insulin-like growth factors (IGF) I and
      II and IGF-binding proteins (IGFBP)-1 through-4 and their relationship was
      determined in the guinea pig. Pregnancy did not stimulate weight gain but reduced
      fat deposition in ad libitum-fed animals and increased weight gain and fat
      deposition in food-restricted animals relative to their respective virginal
      group. Pregnancy increased the abundance of circulating IGF-I regardless of food
      intake and increased that of IGF-II in food-restricted animals only. Pregnancy
      also increased circulating IGFBP-1 and -2 in ad libitum-fed and food-restricted
      animals and IGFBP-4 in ad libitum-fed animals. Multiple regression analysis
      showed that maternal weight gain was negatively associated with circulating IGF
      II and IGFBP-2. Fetal weight was positively associated with maternal circulating
      IGF-II and negatively associated with maternal circulating IGFBP-1 and -2.
      Significant interactions indicate, however, that the role of IGF-II and IGFBP-1
      on fetal growth is dependent on the nutritional status of the mother.

PMID- 9530124
TI  - Diurnal rhythm returns to normal after elimination of portacaval shunting.
AB  - Previous studies showed that portacaval shunting causes metabolic and behavioral
      changes in rats. Most metabolic changes reversed within 1-2 wk after restoration
      of normal circulation. However, the rate of cerebral glucose metabolism (CMRGlc)
      remained depressed in some areas. The question arose whether complete recovery
      was possible. Therefore, a long-term behavioral study was undertaken to determine
      the time course of recovery. Diurnal activity was monitored for 48 h each week
      over a period of 14 wk: 2 wk before shunting, 6 wk after shunting, and 6 wk after
      restoration of normal hepatic circulation. Nighttime activity was depressed
      within 1 wk of shunting and did not change. Normal circulation to the liver was
      reestablished after 6 wk. The diurnal cycle was normal 3 wk later. Thus, although
      recovery of the diurnal rhythm is possible, the relatively long period necessary
      suggests the correction of a significant structural or chemical abnormality. A
      study of CMRGlc was made using the behavioral study as an index of the time
      necessary for recovery. CMRGlc returned to normal throughout the brain 6 wk after
      cessation of shunting except in the hippocampus and amygdala (7-8% decrease).

PMID- 9530125
TI  - Effects of physical exercise on phospholipid fatty acid composition in skeletal
      muscle.
AB  - The effects of low-intensity exercise on the fatty acid composition in skeletal
      muscle and in serum were studied in 19 sedentary, middle-aged Swedish men. During
      a 10-wk period, all subjects were given a standardized diet with an identical fat
      composition. After 4 wk on this diet, they were randomly allocated to a daily
      exercise program (55% peak oxygen uptake) or to continue to live a sedentary life
      for the remaining 6 wk. Aerobic capacity (submaximal bicycle test) and peripheral
      insulin sensitivity (hyperinsulinemic euglycemic clamp) improved with training,
      whereas the body weight as well as the body composition (underwater weighing and
      bioimpedance) were unchanged. The proportions of palmitic acid (16:0) and
      linoleic acid [18:2(n-6)] and the sum of n-6 fatty acids [18:2(n-6), 20:3(n-6),
      20:4(n-6)] were decreased in skeletal muscle phospholipids, whereas the
      proportion of oleic acid [18:1(n-9)] was increased, by training. The fatty acid
      profile in skeletal muscle triglycerides remained unchanged. We conclude that
      regular low-intensity exercise influences the fatty acid composition of the
      phospholipids in skeletal muscle, which hypothetically may contribute to changes
      of the skeletal muscle membrane fluidity and influence the peripheral insulin
      sensitivity.

PMID- 9530127
TI  - Minimal influence of blood flow on interstitial glucose and lactate-normal and
      insulin-resistant muscle.
AB  - To study the regulation of the interstitial glucose concentration in skeletal
      muscle, nine control subjects and nine older and overweight non-insulin-dependent
      diabetes mellitus (NIDDM) subjects with extreme insulin resistance were
      investigated with microdialysis in the medial femoral muscle before and during a
      euglycemic insulin clamp. After an overnight fast, arterial plasma glucose
      concentration was 4.9 +/- 0.1 and 8.5 +/- 0.6 mmol/l (P < 0.001), respectively.
      The arterial-interstitial concentration ([a-i]) differences of glucose and
      lactate were 0.43 +/- 0.16 (P < 0.05) and -0.13 +/- 0.05 mmol/l, respectively, in
      normal subjects. In NIDDM subjects, [a-i] differences for glucose and lactate
      were nonsignificant. Muscle blood flow was similar in controls and NIDDM
      subjects. During the glucose clamp, the glucose [a-i] differences increased and
      the lactate [a-i] differences decreased significantly in both groups. The glucose
      170 infusion rate was 8.0 +/- 0.77 vs. 3.2 +/- 0.51 mg.kg-1.min-1 (P < 0.001),
      and blood flow was 9.9 +/- 1.6 vs. 6.7 +/- 0.9 ml.100 g-1.min-1 (P < 0.05) in
      controls and NIDDM subjects, respectively. These results show that 1) the
      capillary wall is rate limiting for muscle glucose uptake and lactate release in
      control subjects but not in postabsorptive hyperglycemic insulin-resistant
      subjects, 2) vasodilation during insulin infusion does not prevent the increase
      in [a-i] difference of glucose in normal subjects, and 3) in severely insulin
      resistant muscle, the [a-i] difference of glucose is not extended despite lack of
      vasodilation.

PMID- 9530126
TI  - Metabolic-cytokine responses to a second immunological challenge with LPS in mice
      with T. gondii infection.
AB  - Injection of 10 cysts of Toxoplasma gondii (Me49 strain) into Swiss Webster mice
      results in 1) an acute phase of infection lasting for 2-3 wk, characterized by
      weight loss, and 2) a chronic phase in which surviving mice show either partial
      weight recovery (Gainers) or persistent, although stable, cachexia (Nongainers).
      In response to a second immunological stimulation with lipopolysaccharide (LPS)
      in the chronic phase of the infection, it is shown that 1) the increase in energy
      expenditure was more prolonged in both groups of infected mice than in controls,
      2) the intensity and duration of hypophagia were also differently affected with
      Nongainers > Gainers > controls, and 3) the infected mice had higher serum levels
      of tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-10 and a lower
      ratio of IL-10 to TNF-alpha than controls. In contrast, serum IL-4 increased to
      the same level in all three groups. Evaluation of the permeability of the blood
      brain barrier by intravenous injection of Evans blue revealed a marked staining
      in the brain of only the infected Nongainers. Taken together, these results
      indicate that, in mice with chronic toxoplasmosis, a second nonspecific challenge
      (with LPS) exacerbates the hypophagic and hypermetabolic states, the latter being
      associated with hyperresponsiveness in TNF-alpha and IL-10 production.
      Furthermore, the greater exacerbation of the hypophagic state in mice showing
      persistent cachexia may be due to a preexisting higher permeability of the blood
      brain barrier, which would allow a greater access of plasma-borne cytokines
      and/or other neuroimmunologically active substances to the central nervous
      system.

PMID- 9530128
TI  - Noradrenergic control of central oxytocin release during lactation in rats.
AB  - Noradrenergic systems regulate the systemic release of oxytocin (OT) in lactating
      rats. However, a role for norepinephrine (NE) in release of OT within the
      magnocellular nuclei during suckling has not been established. These studies were
      designed to determine 1) if suckling induces NE release in the supraoptic (SON)
      and paraventricular (PVN) nuclei of conscious rats and 2) the role of NE in the
      central, intranuclear release of OT within these nuclei. Female Holtzman rats
      were implanted with microdialysis probes adjacent to the PVN or SON on lactation
      days 8-12. The following day, the pups were isolated from the dams for 4 h.
      Microdialysis probes were perfused with artificial cerebrospinal fluid (ACSF) or
      with ACSF containing an alpha- or a beta-adrenergic receptor antagonist.
      Dialysate was collected before, during, and after suckling and analyzed for NE or
      OT. In an additional experiment, an alpha- or beta-adrenergic agonist was
      administered via the microdialysis probes into the PVN in nonsuckled, lactating
      rats. Extracellular NE increased in the PVN during suckling but was not
      detectable in the SON. OT concentrations in dialysates from the PVN and SON
      significantly increased during suckling. Blockade of either alpha-(in both PVN
      and SON) or beta- (PVN) adrenergic receptors prevented the suckling-induced
      increase in central OT release. OT release was increased in nonsuckled, lactating
      rats by central application of either an alpha- or beta-adrenergic agonist. These
      data demonstrate that intranuclear NE release is increased in the PVN by suckling
      and that subsequent stimulation of both alpha- and beta-noradrenergic receptors
      mediates intranuclear OT release.

PMID- 9530129
TI  - Insulin release transduction mechanism through acid glucan 1,4-alpha-glucosidase
      activation is Ca2+ regulated.
AB  - An important signal involved in glucose-stimulated insulin secretion is
      transduced through the action of a lysosomal acid, glucan 1,4-alpha-glucosidase.
      We investigated the Ca2+ dependency of this enzyme activity in relation to
      insulin release. In isolated islets, increased levels of extracellular Ca2+
      induced a large increase in acid glucan 1,4-alpha-glucosidase activity
      accompanied by a similar increase in insulin release at both substimulatory and
      stimulatory concentrations of glucose. At low glucose the Ca2+ "inflow" blocker
      nifedipine unexpectedly stimulated enzyme activity without affecting insulin
      release. However, nifedipine suppressed 45Ca2+ outflow from perifused islets at
      low glucose and at Ca2+ deficiency when intracellular Ca2+ was mobilized by
      carbachol. This nifedipine-induced retention of Ca2+ was reflected in increased
      acid glucan 1,4-alpha-glucosidase activity. Adding different physiological Ca2+
      concentrations or nifedipine to islet homogenates did not increase enzyme
      activity. Neither selective glucan 1,4-alpha-glucosidase inhibition nor the
      ensuing suppression of glucose-induced insulin release was overcome by a maximal
      Ca2+ concentration. Hence, Ca(2+)-induced changes in acid glucan 1,4-alpha
      glucosidase activity were intimately coupled to similar changes in Ca(2+)-glucose
      induced insulin release. Ca2+ did not affect the enzyme itself but presumably
      activated either glucan 1,4-alpha-glucosidase-containing organelles or closely
      interconnected messengers.

PMID- 9530130
TI  - beta 3-Adrenergic agonist induces a functionally active uncoupling protein in fat
      and slow-twitch muscle fibers.
AB  - The mitochondrial uncoupling protein (UCP) has usually been found only in brown
      adipose tissue. We recently observed that a chronic administration of the beta 3
      adrenergic agonist CL-316,243 (CL) induced the ectopic expression of UCP in white
      fat and skeletal muscle in genetic obese yellow KK mice. The aim of the present
      study was to examine whether UCP could be induced in nongenetic obese animals
      produced by neonatal injections of monosodium L-glutamate (MSG). The daily
      subcutaneous injection of CL (0.1 mg/kg) to MSG-induced obese mice for 2 wk
      caused significant reductions of body weight (15%) and white fat pad weight
      (58%). Northern and Western blot analyses showed that CL induced significant
      expressions of UCP in the white fat and muscle, as well as in brown fat.
      Immunohistochemical observations revealed that the UCP stains in white fat were
      localized on multilocular cells and that those in muscle were localized on slow
      twitch fibers rich in mitochondria. Immunoelectron microscopy confirmed the
      mitochondrial localization of UCP in the myocytes. The guanosine 5'-diphosphate
      (GDP) binding to mitochondria in brown fat doubled after the CL treatment.
      Moreover, significant GDP binding was detected in the white fat and muscle of the
      CL-treated mice, at about one-fourth and one-thirteenth the activity of brown
      fat, respectively, suggesting that ectopically expressed UCP is functionally
      active. We concluded that the beta 3-adrenergic agonist CL can induce
      functionally active UCP in white fat and slow-twitch muscle fibers of obese mice.

PMID- 9530131
TI  - Ovariectomy augments B lymphopoiesis and generation of monocyte-macrophage
      precursors in rat bone marrow.
AB  - To investigate the effects of estrogen depletion on hematopoiesis and bone
      turnover, female rats were either ovariectomized (OVX) or sham operated and
      killed at 1, 2, 3, and 4 wk postsurgery. Flow cytometric analysis of bone marrow
      cells (BMC) revealed that, in close temporal association with the rise in bone
      turnover as measured by bone histomorphometry, the number of Thy 1.1+ and KiB1R+
      BMC increased two- to threefold in OVX rats relative to sham controls. The Thy
      1.1+ BMC were further characterized as Thy 1.1+/KiB1R+ and Thy 1.1+/HIS24+ double
      positive cells of the B cell lineage. A transient rise in ED1+ myeloid cells
      expressing a lysosomal antigen specific for the monocyte-macrophage and
      osteoclast lineage coincided with the upregulation of osteoclast numbers in OVX
      rats at 2 wk postsurgery, but the number of ED8+ myelomonocytic BMC remained
      unchanged. Administration of estradiol prevented the rise in Thy 1.1+, KiB1R+,
      and ED1+ BMC in OVX animals. Our study indicates that ovariectomy upregulates B
      lymphopoiesis in rat bone marrow and increases myeloid cell differentiation into
      the monocyte-macrophage and possibly also the osteoclast lineage.

PMID- 9530132
TI  - Metabolism of skin and muscle protein is regulated differently in response to
      nutrition.
AB  - We have measured skin and muscle protein kinetics and amino acid (AA) transport
      in anesthetized rabbits during 1) 64-h fast, 2) AA infusion, 3) AA plus fat
      emulsion infusion, and 4) AA plus hyperinsulinemia. L-[ring-13C6]phenylalanine
      was infused as the tracer, and the ear and hindlimb were used as arteriovenous
      units to reflect skin and muscle protein kinetics, respectively. Skin protein net
      balance was not different from zero in all groups, indicating a maintenance of
      protein mass. In contrast, the muscle net balance differed over a range from -1.6
      +/- 0.6 after fasting to 0.2 +/- 0.2 mumol.100 g-1.h-1 during hyperinsulinemia.
      In the skin, 59-66% of intracellular free phenylalanine came from proteolysis,
      and phenylalanine availability from proteolysis was positively correlated to the
      protein synthesis rate. In conclusion, normal skin maintains its constant protein
      mass by efficient reutilization of AAs from proteolysis. In contrast to muscle,
      skin protein is relatively insensitive to control by nutritional and hormonal
      factors. Because of the metabolic differences, when limb models are used for
      muscle protein metabolism, the potential contribution by limb skin should be
      considered.

PMID- 9530133
TI  - Glucose stimulates transcription of fatty acid synthase and malic enzyme in avian
      hepatocytes.
AB  - Transcription of fatty acid synthase (FAS) and malic enzyme (ME) in avian liver
      is low during starvation or feeding a low-carbohydrate, high-fat diet and high
      during feeding a high-carbohydrate, low-fat diet. The role of glucose in the
      nutritional control of FAS and ME was investigated by determining the effects of
      this metabolic fuel on expression of FAS and ME in primary cultures of chick
      embryo hepatocytes. In the presence of triiodothyronine, glucose (25 mM)
      stimulated an increase in the activity and mRNA abundance of FAS and ME. These
      effects required the phosphorylation of glucose to glucose 6-phosphate but not
      further metabolism downstream of the aldolase step of the glycolytic pathway.
      Xylitol mimicked the effects of glucose on FAS and ME expression, suggesting that
      an intermediate of the pentose phosphate pathway may be involved in mediating
      this response. The effects of glucose on the mRNA abundance of FAS and ME were
      accompanied by similar changes in transcription of FAS and ME. These data support
      the hypothesis that glucose plays a role in mediating the effects of nutritional
      manipulation on transcription of FAS and ME in liver.

PMID- 9530134
TI  - Human syncytiotrophoblast NPY receptors are located on BBM and activate PLC-to
      PKC axis.
AB  - Neuropeptide Y (NPY) is abundant in plasma and amniotic fluid of women throughout
      pregnancy, during which its involvement in placental hormonogenesis has been
      proposed. In accordance with its putative role, the aim of this study was to
      characterize the human placental syncytiotrophoblast receptivity to NPY. Thus we
      performed this study on brush-border membranes (BBM) and basal plasma membranes
      (BPM). Specific 125I-labeled NPY (125I-NPY) binding to BBM was rapid (20 min),
      saturable, with a maximum binding capacity of 604 +/- 100 fmol/mg protein, and of
      high affinity, with a dissociation constant of 11 +/- 3 nM. No saturable binding
      could be shown in BPM. The rank order of affinity of NPY and related peptides to
      compete for 125I-NPY binding sites was peptides YY (PYY) > NPY = [Leu31,Pro34]NPY
      > 13-36NPY >> pancreatic polypeptide (PP). It is noteworthy that PYY displaced
      only 45% of the binding sites. In BBM, both NPY and PYY were potent phospholipase
      C (PLC) stimulators, leading to a four- to fivefold increase of control
      phosphodiesterase activity. The latter effect could be prevented by preincubation
      of membranes with 5 microM U-73122, a known inhibitor of G protein-linked
      receptor activation of PLC-beta. Furthermore, 5 microM BIBP-3226, a Y1-receptor
      antagonist, shifted both dose-response curves to the right in a similar fashion
      for both peptides. In accordance with the PLC stimulation, both peptides also
      induced stimulation of protein kinase C (PKC) activity, which could be partially
      but additively prevented by U-73122 and LY-294002, a selective inhibitor of
      phosphatidyl-inositol-3 kinase (PI3K). Taken together, these data suggest that
      placental and blood-derived NPY binds to a mixed population of receptors composed
      of Y1 and Y3 subtypes on the maternal side of the syncytiotrophoblast, where it
      can mediate its physiological purposes via PLC-beta and PI3K activation, both of
      which lead to PKC activation. However, because BIBP-3226 antagonized both
      effects, the physiological relevance of the apparent Y3 fraction is still
      unsolved.

PMID- 9530135
TI  - Regulation of fatty acid oxidation in untrained vs. trained men during exercise.
AB  - We have recently shown that increased carbohydrate flux decreases fat oxidation
      during exercise by inhibition of fatty acid entry into the mitochondria. Because
      endurance training reduces the rate of carbohydrate flux during exercise, we
      hypothesized that training increases fat oxidation by relieving this inhibition.
      To test this hypothesis, five sedentary and five endurance-trained men exercised
      on a cycle ergometer at an oxygen consumption (VO2) of approximately 2.0 l/min,
      representing 80 and 40% peak VO2, respectively. [1-13C]oleate and [1
      14C]octanoate, long- and medium-chain fatty acids, respectively, were infused for
      the duration of the studies. Carbohydrate oxidation was significantly higher in
      the sedentary group (196 +/- 9 vs. 102 +/- 17 mumol.kg-1.min-1, P < 0.05). Oleate
      oxidation was higher in the trained group (3.8 +/- 0.6 vs. 1.9 +/- 0.3 mumol.kg
      1.min-1, P < 0.05), whereas octanoate oxidation was not different between the two
      groups. The percentage of oleate that was taken up by tissues and oxidized was
      higher in the trained group (76 +/- 7 vs. 58 +/- 3%, P < 0.05). However, the
      percentage of octanoate taken up and oxidized was not different (82 +/- 3 vs. 85
      +/- 4%, not significant). Because octanoate, unlike oleate, can freely diffuse
      across the mitochondrial membrane, the present results suggest that the
      difference in fatty acid oxidation between trained and untrained individuals may
      be due to enhanced fatty acid entry into the mitochondria.

PMID- 9530136
TI  - Distinct localization of GLUT-1, -3, and -5 in human monocyte-derived
      macrophages: effects of cell activation.
AB  - We determined subcellular localization of GLUT-1, GLUT-3, and GLUT-5 as human
      monocytes differentiate into macrophages in culture, and effects of the
      activating agents N-formyl-methionyl-leucyl-phenylalanine (fMLP) and phorbol
      myristate acetate (PMA). Western blot analysis demonstrated progressively
      increased GLUT-1, rapidly decreased GLUT-3, and a delayed increase of GLUT-5
      expression during differentiation. Confocal microscopy revealed that each isoform
      displayed a unique subcellular distribution and cell-activation response. GLUT-1
      was localized primarily to the cell surface but was also detected in the
      perinuclear region in a pattern characteristic of recycling endosomes. GLUT-3
      exhibited predominantly a distinct vesicle-like staining but was present only in
      monocytes. GLUT-5 was found primarily at the cell surface but was detectable
      intracellularly. Activation with fMLP induced similar GLUT-1 and GLUT-5
      redistributions from intracellular compartments toward the cell surface. PMA
      elicited a similar translocation of GLUT-1, but GLUT-5 was redistributed from the
      plasma membrane to a distinct intracellular compartment that appeared connected
      to the cell surface. These results suggest specific subcellular targeting of each
      transporter isoform and differential regulation of their trafficking pathways in
      cultured macrophages.

PMID- 9530137
TI  - Brown fat is essential for cold-induced thermogenesis but not for obesity
      resistance in aP2-Ucp mice.
AB  - The role of brown adipose tissue in total energy balance and cold-induced
      thermogenesis was studied. Mice expressing mitochondrial uncoupling protein 1
      (UCP-1) from the fat-specific aP2 gene promoter (heterozygous and homozygous aP2
      Ucp transgenic mice) and their nontransgenic C57BL6/J littermates were used. The
      transgenic animals are resistant to obesity induced by a high-fat diet,
      presumably due to ectopic synthesis of UCP-1 in white fat. These animals
      exhibited atrophy of brown adipose tissue, as indicated by smaller size of brown
      fat and reduction of its total UCP-1 and DNA contents. Norepinephrine-induced
      respiration (measured in pentobarbital sodium-anesthetized animals) was decreased
      proportionally to the dosage of the transgene, and the homozygous (but not
      heterozygous) transgenic mice exhibited a reduction in their capacity to maintain
      body temperature in the cold. Our results indicate that the role of brown fat in
      cold-induced thermogenesis cannot be substituted by increased energy expenditure
      in other tissues.

PMID- 9530139
TI  - Gut mucosal protein synthesis in fed and fasted humans.
AB  - Fractional protein synthesis rate (FSR) of duodenal mucosa was measured in two
      groups of six healthy young men, either in the fed state at the end of a 10-day
      standardized diet or after a 36-h fast. Protein synthesis rate was measured
      during a 9-h intravenous infusion of [13C]leucine and [2H5]phenylalanine. The fed
      group also received an intragastric tracer, [2H3]leucine, mixed with the liquid
      diet. At the end of the tracer infusion, an endoscopy was performed to take
      duodenal mucosal biopsies. The major results were that 1) duodenal mucosal
      protein synthesis was high, 48.0 +/- 8.5% (SE)/day by use of intravenous leucine
      tracer and intracellular leucine enrichment; 2) it was not affected by feeding
      whatever the tracer or the precursor pool used for the calculations; 3) the two
      intravenous tracers gave different FSR values; and 4) with the intragastric
      tracer, FSR was 25-220% of the rate calculated with the intravenous tracer,
      depending on the precursor pool used for the calculation. Thus absolute values of
      FSR should be taken with caution, because they depend on the precursor pool
      chosen, the route of tracer administration, and the tracer itself. However, gut
      mucosal protein synthesis as assessed by an intravenous tracer is not affected by
      feeding in humans.

PMID- 9530138
TI  - Angiotensin II-induced Ca2+ mobilization and prolactin release in normal and
      hyperplastic pituitary cells.
AB  - We evaluated the effects of angiotensin II (ANG II) and its antagonists on
      prolactin release, intracellular calcium ([Ca2+]i) mobilization, and
      [3H]thymidine uptake in cells from normal rat pituitaries and from estrogen
      induced pituitary tumors. ANG II (10(-7) to 10(-9) M) increased prolactin release
      significantly in control and not in tumoral cells. In control cells, ANG II (10(
      6) to 10(-9) M) produced an immediate spike of [Ca2+]i followed by a plateau.
      Spike levels rose significantly between 10(-10) and 10(-8) M ANG II, whereas the
      onset of the spike was retarded with decreasing concentrations. In tumoral cells,
      ANG II did not produce a spike phase even at 10(-6) M. ANG II-induced prolactin
      release and calcium mobilization were blocked by losartan (AT1 receptor
      antagonist) and not by PD-123319 (AT2 antagonist). Finally, [3H]thymidine uptake
      was not modified by ANG II (10(-7) to 10(-10) M) or its antagonists in either
      group. Our results suggest that chronic in vivo estrogenic treatment alters in
      vitro pituitary response to ANG II. Alterations might function to limit excessive
      prolactin secretion of hypersecreting tumors. Besides, ANG II does not modify DNA
      synthesis in vitro of cells from normal or tumor-derived hypophyses.

PMID- 9530140
TI  - Tracer methods underestimate short-term variations in urea production in humans.
AB  - Urea production rate (Ra) is commonly measured using a primed continuous tracer
      urea infusion, but the accuracy of this method has not been clearly established
      in humans. We used intravenous infusions of unlabeled urea to assess the accuracy
      of this technique in normal, postabsorptive men under the following four
      different conditions: 1) tracer [13C]urea was infused under basal conditions for
      12 h (control); 2) tracer [13C]urea was infused for 12 h, and unlabeled urea was
      infused from hours 4 to 12 at a rate twofold greater than the endogenous Ra
      ("step" infusion); 3) tracer [13C]urea was infused for 12 h, and unlabeled urea
      was infused from hours 4 to 8 ("pulse" infusion); and 4) tracer [13C]urea was
      infused for 9 h, and unlabeled alanine was infused at a rate of 120 mg.kg-1.h-1
      (1.35 mmol.kg-1.h-1) from hours 4 to 9. Urea Ra was calculated using the isotopic
      steady-state equation (tracer infusion rate/tracer-to-tracee ratio), Steele's non
      steady-state equation, and urinary urea excretion corrected for changes in total
      body urea. For each subject, endogenous urea Ra was measured at hour 4 of the
      basal condition, and the sum of this rate plus exogenous urea input was
      considered as "true urea input". Under control conditions, urea Ra at hour 4 was
      similar to that measured at hour 12. After 8-h step and 4-h pulse unlabeled urea
      infusions, Steele's non-steady-state equation underestimated true urea input by
      22% (step) and 33% (pulse), whereas the nonisotopic method underestimated true
      urea input by 28% (step) and 10% (pulse). Similar conclusions were derived from
      the alanine infusion. These results indicate that, although Steele's non-steady
      state equation and the nontracer method more accurately predict total urea Ra
      than the steady-state equation, they nevertheless seriously underestimate total
      urea Ra for as long as 8 h after a change in true urea Ra.

PMID- 9530141
TI  - Effect of prior eccentric contractions on lactate/H+ transport in rat skeletal
      muscle.
AB  - The effect of prior eccentric contractions on skeletal muscle lactate/H+
      transport was investigated in rats. Lactate transport was measured in sarcolemmal
      giant vesicles obtained from soleus and red (RG) and white gastrocnemii (WG)
      muscles 2 days after intense eccentric contractions (ECC) and from the
      corresponding contralateral control (CON) muscles. The physiochemical buffer
      capacity was determined in the three muscle types from both ECC and CON legs.
      Furthermore, the effect of prior eccentric contractions on release and muscle
      content of lactate and H+ during and after supramaximal stimulation was examined
      using the perfused rat hindlimb preparation. The lactate transport rate was lower
      (P < 0.05) in vesicles obtained from ECC-WG (29%) and ECC-RG (13%) than in
      vesicles from the CON muscles. The physiochemical buffer capacity was reduced (P
      < 0.05) in ECC-WG (13%) and ECC-RG (9%) compared with the corresponding CON
      muscles. There were only marginal effects on the soleus muscle. Muscle lactate
      concentrations and release of lactate during recovery from intense isometric
      contractions were lower (P < 0.05) in ECC than in CON hindlimbs, indicating
      decreased anaerobic glycogenolysis. In conclusion, the sarcolemmal lactate/H+
      transport capacity and the physiochemical buffer capacity were reduced in prior
      eccentrically stimulated WG and RG in rats, suggesting that muscle pH regulation
      may be impaired after unaccustomed eccentric exercise. In addition, the data
      indicate that the glycogenolytic potential is decreased in muscles exposed to
      prior eccentric contractions.

PMID- 9530143
TI  - Minimal model estimate of glucose effectiveness: role of the minimal model volume
      and of the second hidden compartment.

PMID- 9530142
TI  - Circulatory model in metabolic studies of rapidly renewed hormones: application
      to ANP kinetics.
AB  - In an attempt to identify and quantify the sites of atrial natriuretic peptide
      (ANP) degradation, a new tracer experiment has been developed. 125I-ANP was
      injected as a bolus just upstream from the right atrium, and blood was sampled
      from two different sites (pulmonary artery and aorta) in eight cardiac patients.
      Data were analyzed using a physiologically based circulatory model consisting of
      three blocks in series (right heart, lungs and left heart, and periphery)
      supplied by the same flow (cardiac output, measured by thermodilution); the
      extraction coefficients of the three blocks and of the whole body could be
      determined from the areas under tracer concentration curves in plasma (AUCs). The
      values for AUCs (means +/- SD) were 64.8 +/- 9.4 and 65.5 +/- 10.7% dose.l-1.min
      1 for pulmonary artery and aorta curves, respectively; the area under the
      pulmonary artery curve could be subdivided into the area under the first-pass
      curve (30.6 +/- 4.7% dose. l-1.min-1) and the area under the recirculating curve
      (34.0 +/- 7.7% dose.l-1.min-1). The metabolic clearance rate of 125I-ANP,
      computed as dose divided by the area under the recirculating curve, was 3.1 +/-
      0.7 l/min, and the whole body extraction was 47.6 +/- 6.6%. In our patients with
      myocardial dysfunction, neither right heart block nor lungs and left heart block
      significantly extracted ANP, and periphery block accounted for almost all removal
      of the hormone from the blood.

PMID- 9530144
TI  - Current concepts in mucosal immunity. III. Ontogeny and function of gamma delta T
      cells in the intestine.
AB  - -gamma delta T cells are located in the paracellular space between epithelial
      cells. In the human colon and small intestine, 5-40% of intraepithelial
      lymphocytes (IEL) are gamma delta T cells, and in mice an even greater proportion
      of IEL are gamma delta T cells. The gamma delta T cell receptor repertoire in the
      human intestine undergoes marked changes in V region gene usage and junctional
      diversity during development from fetus to newborn to adult, suggesting that
      gamma delta T cells may mediate qualitatively or quantitatively different
      functions at various stages of development. gamma delta IEL have been shown to
      produce cytokines and growth factors and to influence epithelial cell
      proliferation and differentiation, as well as the mucosal development of
      immunoglobulin A B cells. gamma delta IEL also manifest cytolytic activity.
      However, the ligands recognized by intestinal gamma delta T cells and the role
      they play in intestinal immune responses, in immune defense to enteric pathogens,
      and in the pathogenesis of intestinal disease are thus far largely unknown.

PMID- 9530145
TI  - Tonic and phasic motor activity in the proximal and distal colon of healthy
      humans.
AB  - In healthy humans, meals stimulate phasic and tonic motor activity in the
      unprepared distal colon. The response of the proximal colon remains unknown. In
      this study, we assessed the effect of a liquid meal on proximal and distal
      colonic motor activity. In 12 healthy volunteers, colonic tone and phasic
      motility were simultaneously recorded by using an electronic barostat and
      perfused catheters in the fasting state and in response to a 1,000-kcal meal. The
      meal significantly increased the phasic activity in the distal colon (230 +/- 46%
      of the basal value; P = 0.02) but not in the proximal colon (138 +/- 25% of the
      basal value; P = 0.2). The intrabag volume of the barostat was significantly more
      reduced in the distal than in the proximal colon (74 +/- 11 vs. 50 +/- 9% of the
      basal values, respectively; P = 0.04). We conclude that the postprandial response
      of the unprepared proximal colon is an immediate tonic contraction that is less
      pronounced than in the distal colon.

PMID- 9530146
TI  - Direct measurement of nitric oxide release in gastric mucosa during ischemia
      reperfusion in rats.
AB  - Nitric oxide (NO) generation in the rat gastric mucosa during ischemia
      reperfusion was measured using an NO-sensitive electrode. Under pentobarbital
      sodium anesthesia, an electrode was inserted into the submucosa from the serous
      membrane side in the fundus. After steady-state baseline recording, the celiac
      artery was clamped for 30 min, and then ischemia-reperfusion was achieved by
      removing the clamp. The clamping of the celiac artery caused a decrease in blood
      flow and an increase in NO level in the gastric tissue. Just after the removal of
      the clamp, the NO level rapidly fell and returned to the baseline level.
      Administration of NG-nitro-L-arginine methyl ester (an NO synthase inhibitor, 30
      mg/kg i.p.) before ischemia significantly attenuated both the increase in NO
      level during ischemia and the formation of acute gastric mucosal lesions observed
      after 60 min reperfusion. Administration of superoxide dismutase (a superoxide
      radical scavenger, 10,000 U/kg i.v.) at the end of ischemia inhibited both the
      rapid decrease in NO level during the reperfusion and the gastric mucosal
      erosions. Because NO and superoxide radical produce a highly reactive
      peroxynitrite, it can be argued that NO has an important pathological role in
      acute gastric mucosal injury induced by ischemia-reperfusion. Our conclusion was
      strongly supported by immunohistochemical staining of nitrotyrosine residues, an
      indication of peroxynitrite formation.

PMID- 9530148
TI  - Nociceptive inhibition of migrating myoelectric complex by nitric oxide and
      monoaminergic pathways in the rat.
AB  - This study investigated the role of nitric oxide (NO) and adrenergic and
      dopaminergic mechanisms in reflex inhibition of the migrating myoelectric complex
      (MMC) after intraperitoneal administration of acid in rats. Acid instilled
      immediately after an activity front inhibited the migrating complex and prolonged
      the cycle length from 13.0 +/- 0.7 to 98.5 +/- 17.2 min (P < 0.001).
      Administration of N omega-nitro-L-arginine, reserpine, or guanetidine before acid
      decreased the prolonged cycle length to 18.1 +/- 2.8 (P < 0.001), 19.0 +/- 2.0 (P
      < 0.001), and 27.5 +/- 9.3 min (P < 0.001), respectively. Similarly, haloperidol
      given before acid shortened the prolonged cycle length to 46.7 +/- 5.2 min (P <
      0.05). There was no effect of phentolamine in combination with propranolol or
      hexamethonium given alone. After intraperitoneal instillation of acid there was
      an increase in the plasma levels of somatostatin and a decrease of calcitonin
      gene-related peptide, but there was no change of neuropeptide Y, vasoactive
      intestinal peptide, substance P, neurokinin A, or neurotensin. The results
      indicate that NO and adrenergic, dopaminergic, and somatostatinergic mechanisms
      cooperate in inhibiting the MMC after nociceptive stimulation of the peritoneum.

PMID- 9530147
TI  - Alteration of gene expression by intestinal epithelial cells precedes colitis in
      interleukin-2-deficient mice.
AB  - Intestinal epithelial cells may be actively involved in the immunoregulatory
      pathways leading to intestinal inflammation. The aim of this study was to assess
      expression by intestinal epithelial cells of cytokines with potential involvement
      in the development of intestinal inflammation in interleukin (IL)-2-deficient [(
      /-)] mice. Wild-type mice, mice heterozygous for the disrupted IL-2 gene, and IL
      2(-/-) mice were studied at 6, 16, and 24 wk of age. The mRNA levels of
      transforming growth factor-beta 1 (TGF-beta 1), tumor necrosis factor-alpha (TNF
      alpha), IL-1 beta, IL-6, IL-15, KC, JE, and CD14 in colonic and small intestinal
      epithelial cells were assessed by Northern blot analysis. CD14 was also measured
      by Western blotting and reverse transcriptase polymerase chain reaction (RT-PCR).
      TGF-beta 1 mRNA was constitutively expressed in both colonic and small intestinal
      epithelial cells with increased expression in the colonic epithelium of colitic
      mice. CD14 was detected only in colonic epithelial cells, and mRNA levels
      increased severalfold in IL-2(-/-) mice with colitis. Northern analysis
      demonstrated increased levels of TGF-beta 1 and CD14 mRNA in colonic epithelial
      cells of IL-2(-/-) mice before the development of signs of colitis. CD14 mRNA and
      protein expression in the epithelial cells of colitic mice were confirmed by RT
      PCR and Western blot analysis of isolated cells. In addition, IL-2(-/-) mice also
      expressed increased levels of IL-15 mRNA in small intestinal and colonic
      epithelial cells compared with heterozygous control mice. TNF-alpha, IL-1 beta,
      IL-6, KC, and JE mRNAs were only detectable in colonic epithelial cells of mice
      after the onset of colitis. Enhanced expression of TGF-beta 1, IL-15, and CD14 by
      colonic epithelial cells may play a role in the subsequent development of colitis
      in IL-2(-/-) mice.

PMID- 9530149
TI  - Postsynaptic enhancement by motilin of muscarinic receptor cation currents in
      duodenal smooth muscle.
AB  - We have investigated a potential role of motilin in amplifying the postsynaptic
      muscarinic responses in the rabbit duodenal smooth muscle cells, using the whole
      cell variant of patch-clamp technique. Stimulation of motilin receptors by
      exogenously applied motilin (1 nM) resulted in a large increase in carbachol
      (CCh)-induced atropine-sensitive cation current (ICCh) at threshold
      concentrations of CCh (0.3-1 microM) at 30 degrees C. This potentiation was
      abolished in the presence of a specific blocker of motilin receptor (GM109) and
      was attenuated with increased concentrations of either motilin or CCh, being
      virtually absent with maximally effective concentrations of these agonists.
      Motilin failed to potentiate ICCh when the ambient temperature was reduced to 20
      degrees C or if the cation current had been directly activated by internal
      perfusion with guanosine 5'-O-(3-thiotriphosphate) (50 microM) bypassing the
      muscarinic receptor. These results suggest that some biochemical processes, such
      as enzymatic reactions, might be involved in the motilin-induced potentiation and
      that its site of action might be the muscarinic receptor and/or associated G
      proteins.

PMID- 9530150
TI  - PGE2 hyperpolarizes gallbladder neurons and inhibits synaptic potentials in
      gallbladder ganglia.
AB  - Gallbladder prostaglandin E2 (PGE2) levels are significantly elevated in
      pathophysiological conditions, resulting in changes in gallbladder motility or
      secretion that may involve actions of the prostanoid in intramural ganglia. This
      study was undertaken to examine the effects of PGE2 on neurons of the intramural
      ganglia of the guinea pig gallbladder. Application of PGE2 by microejection or
      superfusion elicited a complex triphasic change in the resting membrane potential
      (RMP). For example, application of PGE2 by microejection (100 microM) resulted in
      a brief hyperpolarization (mean duration 11.1 +/- 1.3 s), followed by a mid-phase
      repolarization toward or above RMP (mean duration 50.7 +/- 8.1 s), and finally a
      long-lasting hyperpolarization (mean duration 157.3 +/- 36.7 s). Associated with
      these PGE2-evoked alterations in RMP were changes in input resistance measured
      via injection of hyperpolarizing current pulses. An examination of the action
      potential afterhyperpolarization (AHP) during the PGE2-evoked response revealed
      an attenuation of both the amplitude and duration of the AHP. However, only a
      slight increase in excitability of gallbladder neurons in the presence of PGE2
      was evident in response to depolarizing current pulses, and PGE2 did not cause
      the cells to fire spontaneous action potentials. Application of PGE2 reduced the
      amplitudes of both fast and slow excitatory synaptic potentials. These results
      suggest that increased prostaglandin production may decrease ganglionic output
      and therefore contribute to gallbladder stasis.

PMID- 9530151
TI  - Development of gastric slow waves in preterm infants measured by
      electrogastrography.
AB  - The aim of this study was to investigate the developmental process of gastric
      myoelectrical activity (GMA) in preterm infants. Nineteen healthy preterm infants
      were studied. GMA was recorded using surface electrogastrography, and six follow
      up studies were performed in each subject. Spectral analysis methods were applied
      to compute the parameters of the electrogastrogram (EGG). The results showed that
      there was a developmental process of GMA with age during the first 6 mo of life.
      1) The percentage of normal slow waves showed a progressive increase after birth
      (36.7 +/- 6.1, 37.8 +/- 6.2, 47.0 +/- 10.0, 52.2 +/- 12.2, 55.2 +/- 9.7, and 65.8
      +/- 13.5% at 1 and 2 wk and 1, 2, 4, and 6 mo, respectively); 2) there was a
      significant postprandial increase in the percentage of normal slow waves during
      the first 2 mo after birth; and 3) the percentages of normal slow waves for
      different gestation ages were not statistically significant. In conclusion, the
      percentage of normal slow waves is low at birth and there is a developmental
      process that may be stimulated by enteral feeding.

PMID- 9530152
TI  - Cell volume regulates liver phosphoenolpyruvate carboxykinase and fructose-1,6
      bisphosphatase genes.
AB  - Hypertonic-induced cell shrinkage increases glucose release in H-4-II-E rat
      hepatoma cells. This is paralleled by a concomitant increase in the mRNA levels
      of the rate-limiting enzymes of the pathway of gluconeogenesis,
      phosphoenolpyruvate carboxykinase (PCK) and fructose-1,6-bisphosphatase (FBP), of
      seven- and fivefold, respectively. In contrast, hypotonic-induced swelling of the
      cells results in a transient decrease in PCK and FBP mRNAs to 15% and 39% of
      control levels. The antagonistic effects of hyper- and hypotonicity mimic the
      counteracting effects of adenosine 3',5'-cyclic monophosphate (cAMP) and insulin
      on PCK and FBP mRNA levels. The hypertonic-induced increase in mRNA levels is due
      to an enhanced transcriptional rate, whereas the decrease in mRNAs caused by
      hypotonicity results from a decrease in transcription as well as mRNA stability.
      The inductive effect of hypertonicity does not require ongoing protein synthesis
      and acts independently of the cAMP-dependent protein kinase and protein kinase C
      pathways. These results suggest that cell volume changes in liver cells may play
      an important role in regulating hepatic glucose metabolism by altered gene
      expression.

PMID- 9530153
TI  - Nonionic diffusion of short-chain fatty acids across rat colon.
AB  - Short-chain fatty acid (SCFA) transport across the colon may occur by nonionic
      diffusion and/or via apical membrane SCFA-/HCO3- exchange. To examine the
      relative importance of these processes, stripped segments of rat (Ratus ratus)
      proximal and distal colon were studied in Ussing chambers, and the unidirectional
      fluxes of radiolabeled SCFA butyrate, propionate, or weakly metabolized
      isobutyrate were measured. In N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid
      (HEPES) or 1 or 5 mM HCO3- Ringer, decreases in mucosal pH stimulated mucosal-to
      serosal flux (Jm-->s) of all SCFA, decreases in serosal pH stimulated serosal-to
      mucosal flux (Js-->m), and bilateral pH decreases stimulated both fluxes equally.
      These effects were observed whether the SCFA was present on one or both sides of
      the tissue, in both proximal and distal colon, in the absence of luminal Na+, and
      in the presence of either luminal or serosal ouabain. Changes in intracellular pH
      or intracellular [HCO3-] did not account for the effects of extracellular pH.
      Luminal Cl- removal, to evaluate the role of apical membrane Cl-/SCFA- exchange,
      had no effect on Jm-->s but decreased Js-->m 32% at pH 6.5 and 22% at 7.2.
      Increasing SCFA concentration from 1 to 100 mM, at pH 6.4 or 7.4, caused a linear
      increase in Jm-->s. We conclude that SCFA are mainly transported across the rat
      colon by nonionic diffusion.

PMID- 9530154
TI  - Mammalian bombesin receptors are coupled to multiple signal transduction pathways
      in pancreatic acini.
AB  - We investigated the structural requirements for bombesin (BB)-like peptides to
      stimulate amylase secretion in rat pancreatic acini and examined the responsible
      intracellular signal transduction pathways. The tetradecapeptide BB-(1-14) was a
      full agonist, whereas the heptapeptide BB-(8-14) did not evoke amylase secretion.
      The mammalian BB analog neuromedin C decapeptide [NMC-(5-14)] was as potent as BB
      (1-14) in stimulating amylase secretion, suggesting that Gly5-Asn6-His7 (or Gln7)
      of the COOH-terminal decapeptide are essential amino acids for full biological
      activity. BB and NMC equipotently stimulated D-myo-inositol 1,4,5-trisphosphate
      production, which was inhibited by the phospholipase C (PLC) inhibitor U-73122.
      BB and NMC also stimulated protein tyrosine kinase (PTK) activities. The half
      maximal effective concentration (EC50) for NMC-activated PTK was 2 log units less
      than the EC50 for BB-activated PTK. NMC was 10-34 times more potent than BB in
      increasing leukotriene C4 (an index of arachidonic acid production). The
      production of leukotriene C4 was inhibited by the phospholipase A2 (PLA2)
      inhibitor ONO-RS-082. NMC is structurally homologous to BB-(5-14) except that
      Gln7 in BB is replaced by His7 in NMC. Therefore, substitution of Gln7 for His7
      may alter the signal transduction systems to include the PTK and PLA2 pathways. U
      73122 inhibited Ca2+ spiking and amylase secretion induced by NMC and BB.
      However, the PTK inhibitor genistein and the PLA2 inhibitor ONO-RS-082 inhibited
      secretion induced by NMC but not that induced by BB. In contrast to nonmammalian
      BB receptors, which primarily use the PLC pathway, the rat BB receptor is linked
      to three different signal transduction systems: PLC, PTK, and PLA2 pathways.

PMID- 9530156
TI  - Differential susceptibility of inbred mouse strains to dextran sulfate sodium
      induced colitis.
AB  - Dextran sulfate sodium (DSS)-induced murine colitis represents an experimental
      model for human inflammatory bowel disease. The aim of this study was to screen
      various inbred strains of mice for genetically determined differences in
      susceptibility to DSS-induced colitis. Mice of strains C3H/HeJ, C3H/HeJBir,
      C57BL/6J, DBA/2J, NOD/LtJ, NOD/LtSz-Prkdc(scid)/Prkdc(scid), 129/SvPas, NON/LtJ,
      and NON.NOD-H2g7 were fed 3.5% DSS in drinking water for 5 days and necropsied 16
      days later. Ceca and colons were scored for histological lesions based on
      severity, ulceration, hyperplasia, and area involved. Image analysis was used to
      quantitate the proportion of cecum ulcerated. Histological examination revealed
      significant differences among inbred strains for all parameters scored. In both
      cecum and colon, C3H/HeJ and a recently selected substrain, C3H/HeJBir, were
      highly DSS susceptible. NOD/LtJ, an autoimmune-prone strain, and NOD/LtSz
      Prkdc(scid)/Prkdc(scid), a stock with multiple defects in innate and adoptive
      immunity, were also highly DSS susceptible. NON/LtJ, a strain closely related to
      NOD, was quite DSS resistant. The major histocompatibility (MHC) haplotype of NOD
      mice (H2g7), a major component of the NOD autoimmune susceptibility, was not
      crucial in determining DSS susceptibility, since NON mice congenic for this MHC
      haplotype retained resistance. C57BL/6J, 129/SvPas, and DBA/2J mice showed
      various degrees of susceptibility, depending upon the anatomical site. A greater
      male susceptibility to DSS-induced colonic but not cecal lesions was observed. In
      summary, this study demonstrates major differences in genetic susceptibility to
      DSS-induced colitis among inbred strains of mice. Knowledge of these strain
      differences in genetic responsiveness to acute inflammatory stress in the large
      intestine will permit design of genetic crosses to elucidate the genes involved.

PMID- 9530155
TI  - DNA methylation contributes to expression of the human neurotensin/neuromedin N
      gene.
AB  - The gut and liver share a common embryological origin. The gene encoding the gut
      hormone neurotensin/neuromedin N (NT/N) is expressed in the adult small bowel,
      and NT/N is transiently expressed in the fetal liver, suppressed in the adult
      liver, and reexpressed in certain liver cancers. In our present study, we found
      that the NT/N gene was expressed at high levels in the human hepatoma cell line
      Hep 3B but was not expressed in Hep G2 cells. To further determine the mechanisms
      regulating NT/N expression, we performed Southern blotting and gene cloning
      techniques. Neither alteration nor mutation of the NT/N gene was responsible for
      this differential NT/N expression pattern. Human NT/N promoter constructs were
      transfected into either Hep 3B or Hep G2. Both cell lines supported NT/N
      transcription, indicating that the absence of NT/N expression in Hep G2 cells was
      due to mechanisms other than the absence of positive transcription factors. The
      role of DNA methylation was next assessed. Methylation of NT/N promoter
      constructs in vitro resulted in a 67-fold reduction in promoter activity, whereas
      treatment with the demethylating agent 5-azacytidine induced NT/N expression in
      Hep G2 cells, thus suggesting that DNA methylation plays a role in the expression
      of the gut endocrine gene NT/N. Defining the mechanisms regulating NT/N
      expression in these hepatic-derived cell lines will provide not only a better
      understanding of cell-specific and developmental regulation of a gut endocrine
      gene but also possible insight into liver cell lineage patterns and the
      derivation of certain hepatocellular cancers.

PMID- 9530157
TI  - Vagal involvement in dietary regulation of nutrient transport.
AB  - In omnivores, gradual alterations in dietary nutrient composition are observed.
      To efficiently absorb dietary nutrients these animals alter intestinal nutrient
      transporter expression to match the pattern of nutrient intake. This often
      involves reprogramming the crypt cell to express greater numbers of the relevant
      transport system. The aim of this study was to determine whether vagal afferents
      are involved in this adaptive process. Guinea pigs were habituated to a low
      carbohydrate diet and then switched to a high-carbohydrate diet. The resultant
      increase in glucose transporter expression was assessed by determining rates of
      glucose transport in jejunal brush-border membrane vesicles. Ablation of vagal
      afferents was accomplished by application of capsaicin to exposed cervical vagi
      and confirmed using Fast blue tracer studies. We found that animals in which
      vagal afferents were ablated with capsaicin were unable to alter rates of glucose
      transport in response to an increase in dietary carbohydrate. This suggests that
      vagal afferents are involved in this adaptive process. These findings support a
      role for the vagus nerve in regulating intestinal transport function, which may
      be important to consider in clinical disease that involves the vagus nerve.

PMID- 9530158
TI  - Impaired gastric acid secretion in gastrin-deficient mice.
AB  - To further understand the role of the peptide hormone gastrin in the development
      and function of the stomach, we have generated gastrin-deficient mice by gene
      targeting in embryonic stem cells. Mutant mice were viable and fertile, without
      obvious visible abnormalities. However, gastric function was severely affected by
      the loss of gastrin. Basal gastric acid secretion was abolished and could not be
      induced by histamine, carbachol, or gastrin. Histological analysis revealed
      alterations in the two cell types primarily involved in acid secretion, parietal
      and enterochromaffin-like (ECL) cells. Parietal cells were reduced in number with
      an accumulation of immature cells lacking H(+)-K(+)-adenosinetriphosphatase (H(+)
      K(+)-ATPase). ECL cells were positioned closer to the base of the gastric glands,
      with markedly lower expression of histidine decarboxylase. Gastrin administration
      for 6 days reversed the effects of the gastrin deficiency, leading to an increase
      in the number of mature, H(+)-K(+)-ATPase-positive parietal cells and a partial
      restoration of acid secretion. The results show that gastrin is critically
      important for the function of the acid secretory system.

PMID- 9530159
TI  - Hepatic pyruvate dehydrogenase activity in humans: effect of cirrhosis,
      transplantation, and dichloroacetate.
AB  - The liver is the major site for lactate clearance, and liver disease exacerbates
      lactic acidosis during orthotopic liver transplantation (OLT). This study
      assessed pyruvate dehydrogenase (PDH) activity in control, cirrhotic, and graft
      liver to test the hypotheses that 1) liver disease decreases hepatic PDH
      activity, 2) graft PDH activity is inhibited due to protracted ischemia, and 3)
      dichloroacetate (DCA) reverses functional PDH inhibition in cirrhotic and graft
      liver. After having given their informed consent, 43 patients received either DCA
      (80 mg/kg) or aqueous 5% glucose during OLT. Six patients without apparent liver
      dysfunction that were undergoing subtotal hepatic resection served as controls.
      Liver biopsy PDH activity was assayed by measuring [14C]citrate synthesis from
      [14C]oxaloacetate and PDH-derived acetyl-CoA. PDH in the active form (PDHa) in
      cirrhotic and control liver was 5.6 +/- 1.3 (SE) and 57 +/- 10 nmol.g wet wt
      1.min-1, respectively (P < 0.001). Total PDH activity (PDHt) was 21.5 +/- 3.6 and
      264 +/- 27 nmol.g wet wt-1.min-1, respectively (P < 0.001). DCA increased PDHa in
      cirrhotic liver to 22.3 +/- 4.1 nmol.g wet wt-1.min-1 (P < 0.05 vs. no DCA)
      without altering PDHt. Graft liver PDHa was 166 +/- 19 nmol.g wet wt-1.min-1,
      which was not altered by DCA. We conclude that decreased hepatic PDH activity
      secondary to decreased content may underlie lactic acidosis during OLT, which can
      be partially compensated by DCA administration. There is no apparent inhibition
      of graft liver PDH activity after reperfusion.

PMID- 9530160
TI  - The primary and final effector mechanisms required for kinin-induced epithelial
      chloride secretion.
AB  - The short-circuit current technique was used to examine the effects of N2-L
      lysylbradykinin (LBK) on chloride secretion in the mucosae of the mouse
      intestine. It was found to be a potent chloride secretagogue in the mucosa lining
      the colon, jejunum, and cecum, as it is in most mammals, with 2 nM being
      sufficient to cause half-maximal secretion. The extent of the responses was in
      the order cecum > colon > jejunum. In cystic fibrosis (CF) null mice, with no CF
      transmembrane conductance regulator (CFTR) chloride channels, LBK caused no
      chloride secretion, but transporting activities for other ions were revealed.
      Introduction of the human CF gene into the genome of CF null mice at the zygote
      stage restored the chloride secretory activity of LBK, with only minor
      differences in potency. In mice in which the kinin B2 receptor gene had been
      disrupted, LBK had no effect, whereas the responses to forskolin were unchanged.
      Thus the acute effects of kinins on chloride secretion depend uniquely on kinin
      B2 receptors and CFTR chloride channels, which form the primary and final
      effector mechanisms of the secretory process.

PMID- 9530161
TI  - Rectal tone, distensibility, and perception: reproducibility and response to
      different distensions.
AB  - Increasing interest is focusing on the role of intestinal tone, distensibility,
      and mechanosensation in the genesis of abdominal symptoms. Experimental
      approaches usually feature balloon distension of the bowel with measurements of
      perception, tone, and compliance and/or elastance; however, the methodologies are
      standardized incompletely. We examined the reproducibility of repeated
      assessments of sensory perception, basal tone, and compliance and/or elastance of
      the rectum during distension. We also evaluated the response to inflations that
      varied in regard to control of pressure or volume, pattern of distension, and
      rate of inflation. Five healthy volunteers were studied under two separate
      protocols. The first featured a series of experiments on each of 5 days; the
      other consisted of 2 separate days of study. Repeated distensions evoked
      reproducible responses of sensation and compliance and/or elastance on a single
      day, providing a conditioning distension preceded them. Day-to-day variability
      was also sufficiently small to allow valid comparisons to be made on different
      days in healthy persons. The configuration of the distension profile (phasic,
      staircase, or ramp) and the rate of inflation (from 1 to 40 ml/s) had little
      effect on distensibility or perception. Perceptions were sometimes transient and
      sometimes constant, but no relationship was found between these temporal features
      and the magnitude of the stimulus. These observations help provide a basis as to
      how the responses to rectal distension can be best studied.

PMID- 9530162
TI  - Protein kinetics determined in vivo with a multiple-tracer, single-sample
      protocol: application to lactase synthesis.
AB  - Precise analysis of the kinetics of protein/enzyme turnover in vivo has been
      hampered by the need to obtain multiple tissue samples at different times during
      the course of a continuous tracer infusion. We hypothesized that the problem
      could be overcome by using an overlapping (i.e., staggered) infusion of multiple
      stable amino acid isotopomers, which would take the place of multiple tissue
      samples. We have measured, in pigs, the in vivo synthesis rates of precursor
      (rapidly turning over) and mature (slowly turning over) polypeptides of lactase
      phlorizin hydrolase (LPH), a model for glycoprotein synthesis, by using an
      overlapping infusion of [2H3]leucine, [13C1]leucine, [13C1]phenylalanine,
      [2H5]phenylalanine, [13C6]phenylalanine, and [2H8]phenylalanine. Blood samples
      were collected at timed intervals, and the small intestine was collected at the
      end of the infusion. The tracer-to-tracee ratios of each isotopomer were measured
      in the plasma and jejunal free amino acid pools as well as in purified LPH
      polypeptides. These values were used to estimate kinetic parameters in vivo using
      a linear steady-state compartmental model. The fractional synthesis rates of the
      high-mannose, complex glycosylated and mature brush-border LPH polypeptides, so
      determined, were 3.3 +/- 1.1%/min, 17.4 +/- 11%/min, and 0.089 +/- 0.02%/min,
      respectively. We conclude that this multiple-tracer, single-sample protocol is a
      practicable approach to the in vivo measurement of protein fractional synthesis
      rates when only a single tissue sample can be obtained. This method has broad
      application and should be particularly useful for studies in humans.

PMID- 9530163
TI  - Downregulation of a human colonic sialyltransferase by a secondary bile acid and
      a phorbol ester.
AB  - Fecal constituents such as bile acids and increased sialylation of membrane
      glycoproteins by alpha-2,6-sialyltransferase (HST6N-1) may contribute to
      colorectal tumorigenesis. We hypothesized that bile acids and phorbol ester [12-O
      tetradecanoylphorbol-13-acetate (TPA)] would upregulate HST6N-1 in colonic cells.
      However, deoxycholate (DOC) (300 mumol/l), a secondary bile acid, and TPA (20
      ng/ml) decreased expression of an approximately 100-kDa glycoprotein bearing
      alpha-2,6-linked sialic acid in a colon cancer cell line (T84) in vitro. HST6N-1
      mRNA levels were reduced approximately 80% by treatment (< or = 24 h) with DOC or
      TPA but not by cholate, a primary bile acid. Treatment (24 h) with DOC or TPA
      decreased activity of this enzyme to 30% and 13% of control, respectively. These
      effects of DOC and TPA were transcriptional and were mediated by Ca2+ and protein
      kinase C, respectively. Thus DOC and TPA both downregulated, and did not
      upregulate, alpha-2,6-sialyltransferase expression in vitro, but by different
      transduction pathways. As colorectal tumors grow, their progressive removal from
      the fecal milieu that normally downregulates this enzyme may favor invasion and
      metastasis.

PMID- 9530164
TI  - Fluoride stimulates cystic fibrosis transmembrane conductance regulator Cl-
      channel activity.
AB  - While studying the regulation of the cystic fibrosis transmembrane conductance
      regulator (CFTR), we found that addition of F- to the cytosolic surface of
      excised, inside-out membrane patches reversibly increased Cl- current in a dose
      dependent manner. Stimulation required prior phosphorylation and the presence of
      ATP. F- increased current even in the presence of deferoxamine, which chelates
      Al3+, suggesting that stimulation was not due to AlF4-. F- also stimulated
      current in a CFTR variant that lacked a large part of the R domain, suggesting
      that the effect was not mediated via this domain. Studies of single channels
      showed that F- increased the open-state probability by slowing channel closure
      from bursts of activity; the mean closed time between bursts and single-channel
      conductance was not altered. These results suggested that F- influenced
      regulation by the cytosolic domains, most likely the nucleotide-binding domains
      (NBDs). Consistent with this, we found that mutation of a conserved Walker lysine
      in NBD2 changed the relative stimulatory effect of F- compared with wild-type
      CFTR, whereas mutation of the Walker lysine in NBD1 had no effect. Based on these
      and previous data, we speculate that F- interacts with CFTR, possibly via NBD2,
      and slows the rate of channel closure.

PMID- 9530165
TI  - Molecular mechanisms of antioxidant enzyme expression in lung during exposure to
      and recovery from hyperoxia.
AB  - Manganese superoxide dismutase (MnSOD) activity falls approximately 50% in lung
      during 48 h of exposure of adult rats to > 95% O2 (L. B. Clerch and D. Massaro.
      J. Clin. Invest. 91: 499-508, 1993). We now show that hyperoxia also decreased
      MnSOD activity in lungs of adult baboons, making the phenomenon potentially more
      important to humans. In rats, a decrease in lung MnSOD activity during an initial
      48 h of exposure to > 95% O2 and its increase during an immediately subsequent 24
      h in air were due to decreases and increases, respectively, in MnSOD specific
      activity and synthesis rate; the latter was due to altered translational
      efficiency. The concentration in the lung of copper-zinc superoxide dismutase
      mRNA, catalase mRNA, and glutathione peroxidase mRNA, unchanged during the
      initial 48 h of exposure to O2, rose approximately twofold during reexposure to
      O2 after 24 h in air. The demonstration that the fall in MnSOD activity is
      translationally and posttranslationally regulated during the initial exposure to
      hyperoxia suggests that gene transfer to increase MnSOD activity in hyperoxic
      lungs may also require therapy that maintains translational efficiency and MnSOD
      specific activity.

PMID- 9530166
TI  - Changes in pulmonary expression of hexokinase and glucose transporter mRNAs in
      rats adapted to hyperoxia.
AB  - Impairment of lung aconitase activity, citric acid cycle, and mitochondrial
      respiration by hyperoxia necessitates the elevation of glycolysis for energy
      production and of pentose shunt activity for reducing equivalents. The molecular
      mechanisms that allow increased glucose utilization are unknown. Adult male and
      female rats were adapted to sublethal hyperoxia, equivalent to 83% oxygen at sea
      level, or air for 7 days. Lung RNA and protein increased in hyperoxia (197 and
      57%, respectively), whereas total DNA was unchanged. In hyperoxia, lung total
      hexokinase (HK) activity increased threefold, and mRNAs for HK-II and -III were
      specifically upregulated. HK-I mRNA was unchanged. mRNAs for HK-II and -III
      gradually increased during the first 72 h in hyperoxia. HK-II mRNA was
      significantly elevated at 72 h, preceding changes in lung cell populations.
      Although virtually absent in air, HK-II activity was highly expressed in
      hyperoxia. Among lung glucose transporters, specific expression of mRNAs for GLUT
      4 (insulin dependent) and sodium-glucose cotransporter-1 was decreased, whereas
      that for GLUT-1 was minimally changed. Adaptation to hyperoxia involves
      coordinated changes in gene expression for the proteins regulating pulmonary
      glucose transport.

PMID- 9530167
TI  - Quinones increase gamma-glutamyl transpeptidase expression by multiple mechanisms
      in rat lung epithelial cells.
AB  - gamma-Glutamyl transpeptidase (GGT) plays an important role in glutathione (GSH)
      metabolism. GGT expression is increased in oxidant-challenged cells; however, the
      signaling mechanisms involved are uncertain. The present study used 2,3-dimethoxy
      1,4-naphthoquinone (DMNQ), a redox cycling quinone that continuously produced
      H2O2 in rat lung epithelial L2 cells. It was found that DMNQ increased GGT mRNA
      content by increasing transcription, as measured by nuclear run-on. This was
      accompanied by increased GGT specific activity. Cycloheximide, a protein
      synthesis inhibitor, blocked neither the increased GGT mRNA content nor the
      increased GGT transcription rate caused by DMNQ, suggesting that increased GGT
      transcription was a direct rather than secondary response. Previous data from
      this laboratory (R.-M. Liu, H. Hu, T. W. Robinson, and H. J. Forman. Am. J.
      Respir. Cell Mol. Biol. 14: 186-191, 1996) showed that tert-butylhydroquinone
      (TBHQ) increased GGT mRNA content by increasing its stability. TBHQ differs
      markedly from DMNQ in terms of its conjugation with GSH and H2O2 generation.
      Together, the data suggest that quinones upregulate GGT through multiple
      mechanisms, increased transcription and posttranscriptional modulation, which are
      apparently mediated through generation of reactive oxygen species and GSH
      conjugated formation, respectively.

PMID- 9530168
TI  - L-arginine prevents lung neutrophil accumulation and preserves pulmonary
      endothelial function after endotoxin.
AB  - L-Arginine supplementation has been shown to restore endothelium-derived nitric
      oxide production in several pathological states. The purpose of this study was to
      examine the effect of administration of exogenous L-arginine on the endotoxin
      induced lung neutrophil accumulation and impairment of endothelium-dependent
      guanosine 3',5'-cyclic monophosphate (cGMP)-mediated pulmonary vasorelaxation in
      rats. Endothelium-dependent relaxation was tested by receptor-dependent
      [acetylcholine (ACh)] and receptor-independent (A-23187) pathways. Endothelium
      independent relaxation was tested with sodium nitroprusside (SNP). In isolated
      pulmonary arterial rings, concentration-response curves were generated with ACh,
      A-23187, and SNP (10(-9) to 10(-6) M) 4 h after endotoxin (500 micrograms/kg
      i.p.) with and without prior administration of L-arginine (300 mg/kg i.p.). Lung
      neutrophil accumulation was determined by myeloperoxidase (MPO) assay. After
      endotoxin, lung neutrophil accumulation was significantly increased (MPO
      activity, 3.8 +/- 0.4 vs. 0.8 +/- 0.1 units/g lung weight in control cells; P <
      0.05), which was prevented by L-arginine treatment (MPO activity, 1.3 +/- 0.3
      units/g lung weight; P < 0.05 vs. endotoxin). Endotoxin produced a significant
      impairment of endothelium-dependent cGMP-mediated pulmonary vasorelaxation by
      receptor-dependent (ACh) and -independent (A-23187) pathways as well as of
      endothelium-independent relaxation (SNP). Prior treatment with L-arginine, but
      not with D-arginine, preserved endothelium-dependent vasorelaxation. Neither L-
      nor D-arginine influenced endotoxin-induced impairment of endothelium
      independent, cGMP-mediated pulmonary vasorelaxation. We conclude that
      administration of exogenous L-arginine prevents endotoxin-induced lung neutrophil
      accumulation and attenuates its associated impairment of endothelium-dependent,
      cGMP-mediated pulmonary vasorelaxation.

PMID- 9530169
TI  - O2 regulates surfactant protein A mRNA transcription and stability in human fetal
      lung in vitro.
AB  - The effect of O2 on surfactant protein (SP) A mRNA transcription and half-life
      was determined in midtrimester human fetal lung tissue cultured in either 20
      (control) or 70% O2. Incubation of tissues in 70% O2 resulted in a 133% increase
      in SP-A mRNA transcription rate compared with control tissues. The SP-A mRNA half
      life was increased by 54% in lung tissues cultured in 70% O2 vs. control tissues.
      Western blot analysis indicated a threefold increase in SP-A in the 70% O2
      condition, demonstrating that O2 regulation of SP-A mRNA levels results in
      corresponding changes in SP-A levels. Primer extension assays were performed to
      determine whether the observed increase in SP-A mRNA levels is secondary to the
      preferential expression of one of the human SP-A genes, SP-A1 or SP-A2.
      Transcripts of both the SP-A1 and SP-A2 genes were increased approximately 100%
      in tissues maintained in 70% O2 compared with control tissues. These data
      demonstrate that O2 regulates human SP-A mRNA levels by both transcriptional and
      posttranscriptional mechanisms. Furthermore, because there is no differential
      effect of O2 on the expression of SP-A1 vs. SP-A2 mRNA, the properties of these
      genes that mediate regulation by O2 must be conserved between the two genes.

PMID- 9530170
TI  - A human forkhead/winged-helix transcription factor expressed in developing
      pulmonary and renal epithelium.
AB  - Members of the forkhead/winged-helix transcription factor family play crucial
      roles during vertebrate development. A human hepatocyte nuclear factor/forkhead
      homolog (HFH)-4 cDNA encoding a 421-amino acid protein was isolated from a human
      fetal lung cDNA library. By Southern blot analysis of human-rodent somatic cell
      hybrid genomic DNA, the human HFH-4 gene localizes to chromosome 17q23-qter. This
      is the locus of another forkhead/winged-helix gene, the interleukin enhancer
      binding factor gene. RNA blot analysis revealed a 2.5-kilobase human HFH-4
      transcript in fetal lung, kidney, and brain as well as in adult reproductive
      tissues, lung, and brain. By in situ hybridization, HFH-4 expression is
      associated with differentiation of the proximal pulmonary epithelium, starting
      during the pseudoglandular stage of human lung development. During human renal
      morphogenesis, HFH-4 is expressed in the developing epithelial cells of the
      ureteric duct, glomerulus, and epithelial vesicles. The unique pattern of HFH-4
      expression during human fetal development suggests a role for this
      forkhead/winged-helix factor during pulmonary and renal epithelial development.

PMID- 9530172
TI  - Nitric oxide inhibits Na+ absorption across cultured alveolar type II monolayers.
AB  - We examined the mechanisms by which nitric oxide (.NO) decreased vectorial Na+
      transport across confluent monolayers of rat alveolar type II (ATII) cells grown
      on permeable supports. Amiloride (10 microM) applied to the apical side of
      monolayers inhibited approximately 90% of the equivalent (Ieq) and the short
      circuit (Isc) current, with an half-maximal inhibitory concentration (IC50) of
      0.85 microM, indicating that Na+ entry into ATII cells occurred through amiloride
      sensitive Na+ channels. .NO generated by spermine NONOate and papa NONOate added
      to both sides of the monolayers decreased Ieq and increased transepithelial
      resistance in a concentration-dependent fashion (IC50 = 0.4 microM .NO). These
      changes were prevented or reversed by addition of oxyhemoglobin (50 microM).
      Incubation of ATII monolayers with 8-bromoguanosine 3',5'-cyclic monophosphate
      (400 microM) had no effect on transepithelial Na+ transport. When the basolateral
      membranes of ATII cells were permeabilized with amphotericin B (10 microM) in the
      presence of a mucosal-to-serosal Na+ gradient (145:25 mM), .NO (generated by 100
      microM papa NONOate) inhibited approximately 60% of the amiloride-sensitive Isc.
      In addition, after permeabilization of the apical membranes, .NO inhibited the
      Isc [a measure of Na(+)-K(+)-adenosinetriphosphatase (ATPase) activity] by
      approximately 60%. We concluded that .NO at noncytotoxic concentrations decreased
      Na+ absorption across cultured ATII monolayers by inhibiting both the amiloride
      sensitive Na+ channels and Na(+)-K(+)-ATPase through guanosine 3',5'-cyclic
      monophosphate-independent mechanisms.

PMID- 9530171
TI  - Constitutive nitric oxide production by rat alveolar macrophages.
AB  - Results from previous studies suggest that alveolar macrophages must be exposed
      to inflammatory stimuli to produce nitric oxide (.NO). In this study, we report
      that naive unstimulated rat alveolar macrophages do produce .NO and attempt to
      characterize this process. Western blot analysis demonstrates that the enzyme
      responsible is an endothelial nitric oxide synthase (eNOS). No brain or inducible
      NOS can be detected. The rate of .NO production is approximately 0.07 nmol.10(6)
      cells-1.h-1, an amount that is less than that produced by the eNOS found in
      alveolar type II or endothelial cells. Alveolar macrophage .NO formation is
      increased in the presence of extracellular L-arginine, incubation medium
      containing magnesium and no calcium, a calcium ionophore (A-23187), or
      methacholine. .NO production is inhibited by NG-nitro-L-arginine methyl ester (L
      NAME) but not by NG-nitro-L-arginine, L-N5-(1-iminomethyl)ornithine
      hydrochloride, or aminoguanidine. Incubation with ATP, ADP, or histamine also
      inhibits .NO formation. Some of these properties are similar to and some are
      different from properties of eNOS in other cell types. Cellular .NO levels do not
      appear to be related to ATP or lactate content. Alveolar macrophage production of
      .NO can be increased approximately threefold in the presence of lung surfactant
      or its major component, dipalmitoyl phosphatidylcholine (DPPC). The DPPC-induced
      increase in .NO formation is time and concentration dependent, can be completely
      inhibited by L-NAME, and does not appear to be related to the degradation of DPPC
      by alveolar macrophages. These results demonstrate that unstimulated alveolar
      macrophages produce .NO via an eNOS and that lung surfactant increases .NO
      formation. This latter effect may be important in maintaining an anti
      inflammatory state in vivo.

PMID- 9530173
TI  - Inhibition of amiloride-sensitive sodium-channel activity in distal lung
      epithelial cells by nitric oxide.
AB  - Distal lung epithelial cells (DLECs) play an active role in fluid clearance from
      the alveolus by virtue of their ability to actively transport Na+ from the
      alveolus to the interstitial space. The present study evaluated the ability of
      activated macrophages to modulate the bioelectric properties of DLECs. Low
      numbers of lipopolysaccharide (LPS)-treated macrophages were able to
      significantly reduce amiloride-sensitive short-circuit current (Isc) without
      affecting total Isc or monolayer resistance. This was associated with a rise in
      the flufenamic acid-sensitive component of the Isc. The effect was reversed by
      the addition of N-monomethyl-L-arginine to the medium, implying a role for nitric
      oxide. We hypothesized that macrophages exerted their effect by expressing
      inducible nitric oxide synthase (iNOS) in DLECs. The products of LPS-treated
      macrophages increased the levels of iNOS protein and mRNA transcripts in DLECs as
      well as causing a rise in iNOS activity. Immunofluorescence microscopy of LPS
      stimulated macrophage-DLEC cocultures with anti-nitrotyrosine antibodies provided
      evidence for the generation of peroxynitrite in macrophages but not in DLECs.
      These data indicate that activated macrophages in the lung may contribute to
      impaired resolution of acute respiratory distress syndrome and suggest a novel
      mechanism whereby nitric oxide might alter cell function by altering its ion
      transporting phenotype.

PMID- 9530174
TI  - Regulation of the depth of surface liquid in bovine trachea.
AB  - The luminal surface of airways is lined by a thin film of airway surface liquid
      (ASL). Physiological regulation of the depth of ASL has not been reported
      previously. In this paper, we have used low-temperature scanning electron
      microscopy of rapidly frozen specimens of bovine tracheal epithelium to
      demonstrate alterations in the depth of ASL in response to the cholinergic
      agonist methacholine. We first established that methacholine selectively
      stimulated airway glands, with maximal secretion at approximately 2 min and a
      return to baseline within approximately 5 min. A 2-min exposure to methacholine
      increased the depth of ASL from 23 to 78 microns. Thereafter, depth decreased
      linearly with time, reaching 32 microns at 30 min. The initial increase in depth
      was blocked by bumetanide, an inhibitor of active chloride secretion, whereas the
      slow decline back to baseline was inhibited by amiloride, a blocker of active
      sodium absorption. We conclude that the methacholine-induced changes in ASL depth
      reflect transient gland secretion followed by liquid absorption across the
      surface epithelium.

PMID- 9530175
TI  - Disruption of normal iron homeostasis after bronchial instillation of an iron
      containing particle.
AB  - The atmosphere constitutes a prime vehicle for the movement and redistribution of
      metals. Metal exposure can be associated with an oxidative stress. We tested the
      hypothesis that, in response to an iron-containing particle, the human
      respiratory tract will demonstrate an increased expression of both lactoferrin
      and ferritin as the host attempts to transport and store the metal in a
      chemically less-reactive form and therefore diminish the oxidative stress the
      particle presents. Subjects (n = 22) were instilled with 20 ml of saline and 20
      ml of an iron-containing particle suspended in saline in a right middle lobe
      bronchus and a lingular bronchus, respectively. At either 1, 2, or 4 days after
      this exposure, the volunteer was lavaged for a sample of the lower respiratory
      tract, and concentrations of L-ferritin, transferrin, and lactoferrin were
      measured by enzyme immunoassay, immunoprecipitin analysis, and enzyme-linked
      immunosorbent assay (ELISA), respectively. Transferrin receptor was also
      quantified by ELISA. The concentrations of L-ferritin in the lavage fluid of lung
      exposed to particles were significantly increased relative to the levels of the
      protein in the segment exposed to saline. Relative to saline instillation,
      transferrin was significantly diminished after exposure to the iron-containing
      particle, whereas both lactoferrin and transferrin receptor concentrations in the
      segment of the lung exposed to the particle were significantly elevated. We
      conclude that instillation of an iron-containing particle was associated with a
      disequilibrium in iron metabolism in the lower respiratory tract. The response
      included increased ferritin and lactoferrin concentrations, whereas transferrin
      concentrations diminished. This coordinated series of reactions by the host
      effects a decrease in the availability of catalytically reactive iron to likely
      diminish the consequent oxidative stress to the human host.

PMID- 9530176
TI  - Identification of a putative surfactant convertase in rat lung as a secreted
      serine carboxylesterase.
AB  - In the alveolar lumen, pulmonary surfactant converts from the contents of
      secreted lamellar bodies to tubular myelin to apoprotein-depleted vesicles during
      respiration. Using an in vitro system, researchers have reported that the
      conversion of tubular myelin to vesicles is blocked by inhibitors of serine
      hydrolase activity and have tentatively ascribed "convertase" activity to a
      diisopropyl fluorophosphate (DFP)-binding protein in mouse bronchoalveolar lavage
      (BAL). We purified and sequenced the homologous enzyme from rat BAL fluid. Amino
      acid sequence from the amino terminus and an internal cyanogen bromide peptide of
      the purified rat DFP-binding protein perfectly match the sequence of the
      carboxylesterase ES-2. Although ES-2 was initially cloned from liver, we found a
      1.8-kilobase mRNA for ES-2 in decreasing relative abundance in rat liver, kidney,
      and lung but not in heart or spleen. Although further studies are required to
      establish the identity between "convertase" and ES-2 or a homologous member of
      the carboxylesterase family, our results raise the possibility that a protein
      with esterase/lipase activity plays a role in extracellular surfactant
      metabolism.

PMID- 9530177
TI  - Synergistic cytotoxicity from nitric oxide and hyperoxia in cultured lung cells.
AB  - Exogenous nitric oxide (NO) is being tested clinically for the treatment of
      pulmonary hypertension in infants and children. In most cases, these patients
      receive simultaneous oxygen (O2) therapy. However, little is known about the
      combined toxicity of NO + hyperoxia. To test this potential toxicity, human
      alveolar epithelial cells (A549 cells) and human lung microvascular endothelial
      lung cells were cultured in room air (control), hyperoxia (95% O2), NO (derived
      from chemical donors), or combined hyperoxia + NO. Control cells grew normally
      over a 6-day study period. In contrast, cell death from hyperoxia was evident
      after 4-5 days, whereas cells neither died nor divided in NO alone. However,
      cells exposed to both NO and hyperoxia began to die on day 2 and died rapidly
      thereafter. This cytotoxic effect was clearly synergistic, and cell death did not
      occur via apoptosis. As an indicator of peroxynitrite formation, nitrotyrosine
      containing proteins were assayed using anti-nitrotyrosine antibodies. Two protein
      bands, at molecular masses of 25 and 35 kDa, were found to be increased in A549
      cells exposed to NO or NO + hyperoxia. These results indicate that combined NO +
      hyperoxia has a synergistic cytotoxic effect on alveolar epithelial and lung
      vascular endothelial cells in culture.

PMID- 9530178
TI  - Repeated allergen inhalations induce DNA synthesis in airway smooth muscle and
      epithelial cells in vivo.
AB  - Airway smooth muscle (ASM) mass appears to be increased in the bronchi of
      patients with chronic severe asthma. Although the precise mechanisms that induce
      these changes are unknown, increases in ASM mass are caused, in part, by ASM cell
      proliferation. After allergen challenge in rats, it has been possible to
      demonstrate an increase in ASM mass by morphometric techniques. To examine
      whether hyperplasia is involved in ASM cell growth in vivo, we investigated
      whether repeated allergen challenges in sensitized Brown Norway rats stimulated
      DNA synthesis in airway epithelial and ASM cells. Animals that were actively
      sensitized to ovalbumin (OA) received either three aerosolized OA or saline
      challenges at 5-day intervals. DNA synthesis was measured by indirect
      immunohistochemical techniques with an anti-bromodeoxyuridine (BrdU) antibody. OA
      inhalations increased ASM mass as determined by morphometry and also induced DNA
      synthesis in both airway epithelial and ASM cells in the airways of sensitized
      animals compared with saline-challenged control animals. ASM mass was increased
      in large- and medium-sized airways but not in small airways. However, the number
      of BrdU-positive ASM cells normalized to basement membrane length was also
      greater in the large- and medium-sized airways compared with that in the small
      airways. When the number of BrdU-positive epithelial cells was normalized to
      basement membrane length, there was no difference among airway sizes and the
      number of BrdU-positive epithelial cells. These data suggest that DNA synthesis
      is induced in both airway epithelial and ASM cells after inhalational antigen
      challenge.

PMID- 9530179
TI  - Localization of clearance receptor in rat lung and trachea: association with
      chondrogenic differentiation.
AB  - The lung is rich in atrial natriuretic peptide binding sites, and the majority of
      them are considered to be the natriuretic peptide clearance receptor (NPR-C). In
      this study, localization of NPR-C in the rat lung and trachea was investigated by
      immunohistochemical analysis with the specific antibody. Positive staining was
      observed in the epithelial cell layers of the trachea and bronchiole and the
      myocardium surrounding the pulmonary vein. Moreover, expression of NPR-C was seen
      in mesenchymal cells; it was especially strong in cells in the perichondrium and
      decreased in chondrocytes in the cartilage. Because mesenchymal cells in the
      perichondrium differentiate to chondrocytes, NPR-C expression is suggested to be
      associated with chondrogenic differentiation. The chondrogenic cell line ATDC5
      was used to study NPR-C expression during chondrogenic differentiation in vitro.
      The undifferentiated ATDC5 cells expressed NPR-C at a much higher level than the
      differentiated ATDC5 cells, in accordance with the observation of the
      immunohistochemical analysis in the cartilage. These findings suggest that NPR-C
      expression is differentially regulated in chondrocytes and that the natriuretic
      peptides may play a role in regulating chondrocyte development in the lung.

PMID- 9530180
TI  - Lung matrix deposition of normal and alkylated plasma fibronectin: response to
      postsurgical sepsis.
AB  - Plasma fibronectin (Fn) can both enhance phagocytic clearance of microparticulate
      debris by macrophages as well as incorporate it into the lung extracellular
      matrix (ECM). The goal of this study was to document that N-ethylmaleimide (NEM)
      treated human plasma Fn (HFn) would lose its ability to incorporate into the lung
      ECM in vivo even though it would retain its ability to stimulate test particle
      phagocytosis and bind to fibrin. Using dual-label immunofluorescence, we compared
      the lung deposition of purified normal HFn and NEM-alkylated HFn (NEM-HFn) after
      their intravenous injection into postoperative nonbacteremic and bacteremic sheep
      in relationship to the localization of endogenous sheep Fn. Two days after a
      sterile surgical thoracotomy, sheep were infused with either 5 x 10(8)
      Pseudomonas aeruginosa (postsurgical bacteremic model) or the diluent
      (nonbacteremic model). They also received a bolus 100-mg injection (5 min) of
      either HFn or NEM-HFn. Analysis of serial lung biopsies harvested at 2-h
      intervals demonstrated little deposition of NEM-HFn compared with HFn in the lung
      interstitial matrix of postoperative nonbacteremic sheep. In contrast, enhanced
      deposition of both HFn and NEM-HFn was observed in the lungs of postoperative
      bacteremic sheep. However, in the lungs of bacteremic sheep, HFn displayed a
      diffuse fibrillar deposition pattern in the lung characteristic of ECM
      incorporation, whereas the enhanced NEM-HFn deposition, especially in the
      interstitial ECM region of the lung, was primarily focal and punctate, with very
      little fibrillar incorporation. Immunofluorescent analysis with antibodies
      specific to fibrinogen, Fn, and lung macrophage surface antigens coupled with
      immunoperoxidase staining for HFn antigen revealed that the punctate fluorescence
      pattern was due to both the binding of HFn to fibrin and its colocalization with
      inflammatory cells. Thus treatment of plasma Fn with low concentrations of NEM
      will limit its normal in vivo fibrillar incorporation into the interstitial ECM
      region of the lung.

PMID- 9530181
TI  - Airway epithelial Fas ligand expression: potential role in modulating bronchial
      inflammation.
AB  - Epithelium-derived Fas ligand is believed to modulate inflammation within various
      tissues. In this paper, we report findings that suggest a similar
      immunoregulatory role for Fas ligand in the lung. First, Fas ligand was localized
      to nonciliated, cuboidal airway epithelial cells (Clara cells) throughout the
      airways in the normal murine lung by employing nonisotopic in situ hybridization
      and immunohistochemistry. Second, gld mutant mice, which express a dysfunctional
      Fas ligand protein, were noted to develop prominent infiltration of inflammatory
      cells in submucosal and peribronchial regions of the upper and lower airways.
      Third, during allergic airway inflammation induced by ovalbumin in mice, cell
      associated staining for Fas ligand mRNA and protein was markedly reduced in the
      airway epithelium. These data suggest that Clara cell-derived Fas ligand may
      control immune activity in the airway; thus alterations in this protective
      mechanism may be involved in the pathogenesis of certain inflammatory conditions
      of the airway, such as asthma.

PMID- 9530182
TI  - Evidence that Calu-3 human airway cells secrete bicarbonate.
AB  - The Calu-3 cell line is being investigated as a model for human submucosal gland
      serous cells. In a previous investigation of basal short-circuit current (Isc) in
      Calu-3 cells, high levels of bumetanide-insensitive basal Isc (approximately 60
      microA/cm2) were measured in cells grown at an air interface. Basal Isc was
      reduced only 7% by bumetanide, and the largest component of basal Isc required
      both Cl- and HCO3- in the bathing solutions. Because Isc could be partially
      inhibited by basolateral 4,4'-dinitrostilbene-2,2'-disulfonic acid and because
      the only known apical exit pathway for anions is the cystic fibrosis
      transmembrane conductance regulator, which has a relatively poor conductance for
      HCO3-, it was concluded that most basal Isc is HCO3(-)-dependent Cl- secretion
      [M. Singh, M. Krouse, S. Moon, and J. J. Wine. Am. J. Physiol. 272 (Lung Cell.
      Mol. Physiol. 16): L690-L698, 1997]. We have now measured isotopic fluxes of 36Cl
      and 22Na+ across short-circuited Calu-3 cells and found that virtually none of
      the basal Isc is Cl- secretion or Na+ absorption. Thus, in contrast to the
      earlier report, we conclude that the major component of basal Isc is HCO3-
      secretion. Stimulation recruits primarily Cl- secretion, as previously proposed.

PMID- 9530183
TI  - Basal metabolism does not account for high O2 consumption in stunned myocardium.
AB  - Myocardial O2 consumption (MVo2) in stunned myocardium is relatively high
      compared with the reduced ventricular function. The mechanism of this "oxygen
      paradox" could occur at different levels: basal metabolism, excitation
      contraction coupling, and energy production. In one previously reported series on
      12 isolated, blood-perfused rabbit hearts, left ventricular systolic and
      diastolic function in stunned myocardium were significantly decreased compared
      with control, whereas total MVo2 was not. The MVo2 for the unloaded contraction
      was overproportionately high for the decreased function in stunned myocardium,
      and contractile efficiency was clearly deteriorated. To assess whether the basal
      metabolism specifically is elevated in stunned myocardium, a second series (n =
      14) with a similar protocol was performed in this study. Basal MVo2 after KCl
      arrest (0.5 +/- 0.3 ml.min-1.100 g-1) was significantly lower than that measured
      after KCl arrest (1.2 +/- 0.5 ml.min-1.100 g-1) in an additional series on
      nonischemic hearts (n = 8). Our conclusion is that basal MVo2 in stunned
      myocardium is not elevated. Thus this O2-consuming portion of total MVo2 is not
      responsible for the inefficiency in stunned myocardium. Instead, a "metabolic
      stunning" occurs at the level of both excitation-contraction coupling and force
      development by the contractile apparatus.

PMID- 9530184
TI  - Measurement of heart rate and Q-T interval in the conscious mouse.
AB  - Transgenic mouse models provided a powerful tool to evaluate the physiological
      significance of altered quantities or characteristics of specific gene products,
      such as cardiac ion channels. We have developed a system to record and analyze
      changes in the electrocardiogram in the mouse using an implantable telemetry
      system. The R-R and Q-T intervals were measured on individual beats and on signal
      averaged complexes derived from 1, 2, or 4 s of contiguous data each hour during
      a 24-h period in three male and three female FVB mice. Duration of averaging had
      minimal effect on the measured Q-T. The Q-T interval was shown to be related to
      the square root of the R-R interval, and an appropriate formula for a rate
      corrected Q-T interval (Q-Tc) was derived. Ketamine anesthesia was shown to
      markedly increase duration and variability in R-R, Q-T, and Q-Tc intervals. In
      conscious animals, variability in Q-T was low across animals and over time,
      suggesting that this should be a sensitive model for detection of changes in the
      Q-T interval in transgenic mice with ion channel defects.

PMID- 9530185
TI  - Response of isolated rat descending vasa recta to bradykinin.
AB  - Outer medullary descending vasa recta (OMDVR) were dissected from the outer
      medullary vascular bundles of young rats, perfused in vitro, and loaded with fura
      2 for measurement of intracellular calcium concentration ([Ca2+]i) by fluorescent
      ratio imaging. Fluorescent video images revealed that fura 2 selectively loads
      into endothelial cells but not pericytes. Bradykinin (BK), at concentrations >
      10(-11) M, elicited an increase in [Ca2+]i from baseline values in the range from
      50 to 100 nM to peak values of 600-800 nM followed by a sustained plateau of 150
      250 nM. The vasopressin V1-receptor agonist [Phe2,Ile3,Orn8]vasopressin
      constricted OMDVR but yielded no observable [Ca2+]i response, a finding that is
      consistent with an endothelial cell origin for the fura 2 fluorescent signal. The
      BK [Ca2+]i response was blocked by the selective BK B2-receptor antagonists D-Arg
      [Hyp3,Thi5.8,D-Phe7]BK and D-Arg-[Hyp3,D-Phe7,Leu8]BK but not the B1 antagonist
      des-Arg9-[Leu8]BK. BK vasodilated microperfused OMDVR that had been
      preconstricted with 10(-8) M angiotensin II. We conclude that the [Ca2+]i
      response of OMDVR endothelia can be selectively studied with fura 2, that BK
      increases endothelial [Ca2+]i via the B2 receptor, and that BK can vasodilate
      descending vasa recta.

PMID- 9530186
TI  - Microsphere-induced bronchial artery vasodilation: role of adenosine,
      prostacyclin, and nitric oxide.
AB  - We previously found that injection of 15-micron microspheres into the bronchial
      artery of sheep decreased bronchial artery resistance. This effect was inhibited
      partially by indomethacin or 8-phenyltheophylline, suggesting that microspheres
      caused release of a dilating prostaglandin and adenosine. To identify the
      prostaglandin and confirm adenosine release, we perfused the bronchial artery in
      anesthetized sheep. In 12 sheep, bronchial artery blood samples were obtained
      before and after the infusion of 1 x 10(6) microspheres or microsphere diluent
      into the bronchial artery. Microspheres, but not diluent, decreased bronchial
      artery resistance by 40% and increased bronchial artery plasma 6
      ketoprostaglandin F1 alpha (194.7 +/- 45.0 to 496.5 +/- 101.3 pg/ml), the stable
      metabolite of prostacyclin, and prostaglandin (PG) F2 alpha (28.1 +/- 4.4 to 46.2
      +/- 9.7 pg/ml). There were no changes in PGD2, PGE2, thromboxane B2, adenosine,
      inosine, or hypoxanthine. Pretreatment with dipyridamole, an adenosine uptake
      inhibitor, did not affect bronchial artery nucleoside concentrations (n = 7).
      Microsphere-induced vasodilation was not enhanced by dipyridamole (n = 9) and was
      not inhibited by either the adenosine receptor antagonist xanthine amine congener
      (n = 4) or the nitric oxide (NO) synthase inhibitor NG-monomethyl-L-arginine (n =
      8). These results do not support a role for either adenosine or NO and suggest
      that microspheres caused bronchial artery vasodilation through release of
      prostacylin and an unidentified vasodilator.

PMID- 9530187
TI  - Hemostatic factors in rabbit limb lymph: relationship to mechanisms regulating
      extravascular coagulation.
AB  - Mechanisms regulating extravascular coagulation in interstitial fluids of
      peripheral tissues are poorly understood, since measurements of hemostatic
      factors in these fluids are unavailable. Because lymph from a body region
      reflects the composition of its interstitial fluid, we measured hemostatic
      factors in limb lymph of rabbits both as activity and as antigen. Mean lymph-to
      plasma activity ratios were the following: fibrinogen, 0.28; prothrombin, 0.26;
      factor X, 0.27; factor VII, 0.17; and factors V and VIII, 0.08. All lymph
      fibrinogen was clottable; fibrin degradation products were absent. Lymph von
      Willebrand factor antigen was < 10% of plasma antigen and consisted primarily of
      lower molecular weight multimers. Mean lymph-to-plasma activity ratio for
      antithrombin was 0.38 and for tissue factor pathway inhibitor the ratio was 0.40.
      Low levels of antithrombin-factor Xa were measurable in lymph. The data are
      compatible with a basal factor VIIa-tissue factor-catalyzed extravascular
      activation of factor X that is prevented from progressing to generation of fibrin
      in limb interstitial fluid and lymph by low levels of factor VIII and factor V
      and by the inhibitory activity of antithrombin and tissue factor pathway
      inhibitor.

PMID- 9530188
TI  - Hepatic venular resistance responses to norepinephrine, isoproterenol, adenosine,
      histamine, and ACh in rabbits.
AB  - Changes in hepatic venous resistance were estimated in rabbits from the hepatic
      venular-inferior vena caval pressure gradient [servo-null micropipettes in 49 +/-
      15 (SD) microns vessels] and the total hepatic blood flow (ultrasound probe
      encircling the hepatic artery and the portal vein). Changes in liver volume, and
      thus vascular capacitance, were estimated from measures of the liver lobe
      thickness. Norepinephrine (NE), isoproterenol (Iso), adenosine (Ado), histamine
      (Hist), or acetylcholine (ACh) was infused into the portal vein at a constant
      rate for 5 min. NE, Hist, and Ado increased hepatic venular pressure, but only NE
      and Hist significantly increased hepatic venular resistance. NE reduced the liver
      thickness, but Hist and Ado caused engorgement. Hepatic blood flow was increased
      by NE and Ado and decreased by ACh. The influence of intraportal vein infusion of
      Iso on the liver vasculature, at doses similar to that of NE, was insignificant.
      We conclude that NE acted on all the hepatic microvasculature, increasing
      resistance and actively decreasing vascular volume. Hist passively induced
      engorgement by increasing outflow resistance, whereas the liver engorgement seen
      with Ado was passively related to the increased blood flow. ACh constricted the
      portal venules but did not change the liver volume.

PMID- 9530189
TI  - Hypothermia preserves function and signaling for mitochondrial biogenesis during
      subsequent ischemia.
AB  - Hypothermia is known to protect myocardium during ischemia, but its role in
      induction of a protective stress response before ischemia has not been evaluated.
      As cold incites stress responses in other tissues, including heat shock protein
      induction and signaling mitochondrial biogenesis, we postulated that hypothermia
      in perfused hearts would produce similar phenomena while reducing injury during
      subsequent ischemia. Studies were performed in isolated perfused rabbit hearts (n
      = 77): a control group (C) and a hypothermic group (H) subjected to decreasing
      infusate temperature from 37 to 31 degrees C over 20 min. Subsequent ischemia
      during cardioplegic arrest at 34 degrees C for 120 min was followed by
      reperfusion. At 15 min of reperfusion, recovery of left ventricular developed
      pressure (LVDP), maximum first derivative of left ventricular pressure (LV
      dP/dtmax), LV -dP/dtmax, and the product of heart rate and LVDP was significantly
      increased in H (P < 0.01) compared with C hearts. Ischemic contracture started
      later in H (97.5 +/- 3.6 min) than in C (67.3 +/- 3.3 min) hearts. Myocardial ATP
      preservation and repletion during ischemia and reperfusion were higher in H than
      in C hearts. mRNA levels of the nuclear-encoded mitochondrial proteins adenine
      nucleotide translocase isoform 1 (ANT1) and beta-F1-adenosine-triphosphatase
      (beta-F1-ATPase) normalized to 28S RNA decreased in C hearts but were preserved
      in H hearts after reperfusion. Inducible heat shock protein (HSP70-1) mRNA was
      elevated nearly 4-fold after ischemia in C hearts and 12-fold in H hearts. These
      data indicate that hypothermia preserves myocardial function and ATP stores
      during subsequent ischemia and reperfusion. Signaling for mitochondrial
      biogenesis indexed by ANT1 and beta-F1-ATPase mRNA levels is also preserved
      during a marked increase in HSP70-1 mRNA.

PMID- 9530190
TI  - Blood pressure and heart rate development in young spontaneously hypertensive
      rats.
AB  - The course of hypertension development in young spontaneously hypertensive rats
      (SHR) was studied by the measurement of changes in systolic blood pressure (BP),
      body weight, and heart rate (HR) at 2, 3, 4, and 6 wk of age. To achieve this, we
      compared inbreeding lines of SHR and Wistar-Kyoto rats (WKY) to determine if
      differences in BP, body weight, or HR were present among inbreeding lines of the
      same strain or between strains. The effect of these differences on the eventual
      level of BP was then assessed. We found that BP began to diverge between SHR and
      WKY at 4 wk of age. Significant differences in systolic BP (24 mmHg) between SHR
      inbreeding lines at 4 wk of age did not affect the BP at 8 wk (172 vs. 170 mmHg).
      Pulse pressure was significantly higher in SHR than in WKY at 4 wk of age. HR was
      elevated in SHR over age-matched WKY at 3 wk of age and positively correlated to
      the level of BP attained by individual animals at 6 wk (P = 0.037). Moreover, WKY
      inbreeding lines showing elevated HR developed higher BP (145 vs. 127 mmHg) at 10
      12 and 20 wk of age. The prehypertensive tachycardia in SHR was investigated
      further and found to result from an increased intrinsic HR. Because HR at 3 wk is
      a genetic trait that can be partitioned into inbreeding lines, and inbreeding
      lines most expressive of this trait showed the highest eventual BP, we conclude
      that prehypertensive tachycardia may be an important first step during
      hypertension development in SHR. Moreover, early elevations in HR are highly
      predictive (r = 0.41) of hypertension occurrence in the animal population
      studied.

PMID- 9530191
TI  - Species variability in angiotensin receptor expression by cultured cardiac
      fibroblasts and the infarcted heart.
AB  - Cardiac fibroblasts, an abundant cell of the left ventricle (LV), proliferate and
      synthesize collagen in the heart after acute injury and during pressure overload
      hypertrophy. From many studies, angiotensin II (ANG II) receptors have been
      implicated in promoting collagen formation by the rat cardiac fibroblast. The
      present study examined species variability in ANG II receptor expression.
      Cultured rat fibroblasts expressed 43,000 +/- 15,000 ANG II (AT1-specific)
      receptors per cell (dissociation constant = 0.92 +/- 0.34 nM), whereas rabbit and
      neonate human cardiac fibroblast cultures expressed few receptors. Angiotensin
      increased intracellular Ca2+ concentration in rats but not in rabbit or human
      cardiac fibroblasts and stimulated arachidonic acid release in rat but not rabbit
      fibroblasts. In situ, 6 days after coronary artery ligation, angiotensin receptor
      expression was increased 34.8 +/- 13.4-fold in the infarcted area relative to the
      noninfarcted tissue in the rat LV, whereas rabbit hearts demonstrated only a 3.2
      +/- 1.6-fold increase in ANG II binding within the infarcted tissue. These
      species differences in receptor expression raise questions as to the role of
      angiotensin as a mediator of collagen formation across species and as a direct
      target of angiotensin-converting enzyme inhibitors to regulate cardiac fibroblast
      function.

PMID- 9530192
TI  - Heart rate dynamics during accentuated sympathovagal interaction.
AB  - Concomitant sympathetic and vagal activation can occur in various physiological
      conditions, but there is limited information on heart rate (HR) behavior during
      the accentuated sympathovagal antagonism. Beat-to-beat HR and blood pressure were
      recorded during intravenous infusion of incremental doses of norepinephrine in 18
      healthy male volunteers (mean age 23 +/- 5 yr). HR and blood pressure spectra and
      two-dimensional Poincare plots were generated from the baseline recordings and
      from the recordings at different doses of norepinephrine. The mean blood pressure
      increased (from 90 +/- 7 to 120 +/- 9 mmHg, P < 0.001), HR decreased (from 60 +/-
      9 to 48 +/- 7 beats/min, P < 0.001), and the high-frequency spectral component of
      HR variability increased (P < 0.001) during the norepinephrine infusion as
      evidence of accentuated sympathovagal interaction. Abrupt aperiodic changes in
      sinus intervals that were not related to respiratory cycles or changes in blood
      pressure occurred in 14 of 18 subjects during the norepinephrine infusions. These
      fluctuations in sinus intervals resulted in a complex or parabola-shaped
      structure of the Poincare plots of successive R-R intervals and a widening of the
      high-frequency spectral peak. In four subjects, the abrupt fluctuations in sinus
      intervals were followed by a sudden onset of fixed R-R interval dynamics with a
      loss of respiratory modulation of HR, resulting in a torpedo-shaped structure of
      the Poincare plots. These data show that HR behavior becomes remarkably unstable
      during accentuated sympathovagal interaction, resembling stochastic dynamics or
      deterministic chaotic behavior. These features of HR dynamics can be better
      identified by dynamic analysis of beat-to-beat behavior of R-R intervals than by
      traditional analysis techniques of HR variability.

PMID- 9530193
TI  - Modulation of quinidine-induced arrhythmias by temperature in perfused rabbit
      heart.
AB  - We used low temperature to slow ion channel kinetics and studied the
      electrophysiological effects of quinidine at different pacing rates in isolated
      rabbit hearts. Fifteen epicardial electrograms together with an endocardial
      monophasic action potential were recorded. Epicardial activation and local
      recovery times were measured. Arrhythmias together with the characteristics of
      their mode of induction and rate were analyzed by epicardial activation sequence
      mapping. In the presence of quinidine, arrhythmias consistent with both triggered
      activity and reentry were observed. At baseline, triggered activity was not
      inducible, even though at 25 degrees C the recovery time was greater than that in
      the presence of quinidine at 36 degrees C. Also, with quinidine, the incidence of
      triggered activity decreased at 30 and 25 degrees C. Therefore prolongation of
      the recovery time per se does not cause triggered activity. Quinidine's use
      dependent effects on conduction and reverse use-dependent effects on recovery
      time were amplified by low temperatures. These findings can be understood in
      terms of the known temperature sensitivities of the kinetics of the membrane ion
      channels responsible for activation and recovery. The results demonstrate that
      temperature can be used as a tool to elucidate mechanisms of drug action.

PMID- 9530194
TI  - Optical mapping of atrioventricular node reveals a conduction barrier between
      atrial and nodal cells.
AB  - The mechanisms responsible for atrioventricular (AV) delay remain unclear, in
      part due to the inability to map electrical activity by conventional
      microelectrode techniques. In this study, voltage-sensitive dyes and imaging
      techniques were refined to detect action potentials (APs) from the small cells
      comprising the AV node and to map activation from the "compact" node. Optical APs
      (124) were recorded from 5 x 5 mm (approximately 0.5-mm depth) AV zones of
      perfused rabbit hearts stained with a voltage-sensitive dye. Signals from the
      node exhibited a set of three spikes; the first and third (peaks I and III) were
      coincident with atrial (A) and ventricular (V) electrograms, respectively. The
      second spike (peak II) represented the firing of midnodal (N) and/or lower nodal
      (NH) cell APs as indicated by their small amplitude, propagation pattern,
      location determined from superimposition of activation maps and histological
      sections of the node region, dependence on depth of focus, and insensitivity to
      tetrodotoxin (TTX). AV delays consisted of tau 1 (49.5 +/- 6.59 ms, 300-ms cycle
      length), the interval between peaks I and II (perhaps AN to N cells), and tau 2
      (57.57 +/- 5.15 ms), the interval between peaks II and III (N to V cells). The
      conductance time across the node was 10.33 +/- 3.21 ms, indicating an apparent
      conduction velocity (theta N) of 0.162 +/- 0.02 m/s (n = 9) that was insensitive
      to TTX. In contrast, tau 1 correlated with changes in AV node delays (measured
      with surface electrodes) caused by changes in heart rate or perfusion with
      acetylcholine. The data provide the first maps of activation across the AV node
      and demonstrate that theta N is faster than previously presumed. These findings
      are inconsistent with theories of decremental conduction and prove the existence
      of a conduction barrier between the atrium and the AV node that is an important
      determinant of AV node delay.

PMID- 9530195
TI  - An increase in intracellular [Na+] during Ca2+ depletion is not related to Ca2+
      paradox damage in rat hearts.
AB  - Ca2+ paradox damage has been suggested to be determined by Na+ entry during Ca2+
      depletion and exchange of Na+ for Ca2+ during Ca2+ repletion. With the use of
      23Na nuclear magnetic resonance, we previously observed a Ca2+ paradox without a
      prior Na+ increase. We have now demonstrated a Na+ increase during Ca2+ and Mg2+
      depletion without the occurrence of the Ca2+ paradox during Ca2+ repletion.
      Isolated rat hearts were perfused for 20 min with a Ca(2+)-free or a Ca(2+)- and
      Mg(2+)-free (Ca2+/Mg(2+)-free) solution under hypothermic conditions (20 and 25
      degrees C). Intracellular Na+ concentration ([Na+]i) increased from 11.9 +/- 1.2
      to 26.9 +/- 5.8 mM (P < 0.001) during Ca2+/Mg(2+)-free perfusion at 20 degrees C,
      whereas no significant change in [Na+]i occurred during 20 min of Ca(2+)-free
      perfusion at 20 degrees C. In addition, we confirmed that [Na+]i did not change
      significantly during 20 min of normothermic Ca(2+)-free perfusion. Creatine
      kinase release during normothermic Ca2+ repletion in the 20 degrees C groups was
      approximately 10% and in the 25 degrees C groups 75% of the release in the
      normothermia group. Recovery of rate-pressure product was approximately 50% in
      the 20 degrees C groups versus 0% in the normothermia group. In conclusion,
      hypothermic Ca2+/Mg(2+)-free perfusion results in a significant increase of
      [Na+]i, which does not contribute to the extent of the Ca2+ paradox on
      normothermic Ca2+ repletion.

PMID- 9530196
TI  - 17 beta-Estradiol reduces vasoconstriction in endothelium-denuded rat aortas
      through inducible NOS.
AB  - Estrogen produces vasodilatation through the induction of nitric oxide synthase
      (NOS) in the endothelium, but there are many reports of endothelium-independent
      effects. In the present study, these processes were investigated in rat aortas
      isolated from ovariectomized rats. Long-term in vitro treatment with 17 beta
      estradiol (10 nM for 24 h) in an organ culture system slightly reduced
      acetylcholine-mediated vasorelaxation in endothelium-intact aortic rings. 17 beta
      Estradiol (1 and 10 nM for 24 h) also attenuated the phenylephrine-induced
      constriction in endothelium-denuded aortas, and this effect was inhibited by the
      NOS inhibitor L-N5-(1-iminoethyl)ornithine hydrochloride, as well as the estrogen
      receptor antagonist ICI-182,780. Furthermore, 17 beta-estradiol treatment (1 and
      10 nM for 24 h) increased nitric oxide production as assessed by the conversion
      of [3H]arginine to [3H]citrulline in endothelium-denuded rat aortas. These
      effects were prevented by the protein synthesis inhibitor cycloheximide. 17 beta
      Estradiol (10 nM for 24 h) treatment also induced the formation of inducible NOS
      (iNOS) protein in aortas. The results indicate that 17 beta-estradiol can
      attenuate the vasoconstrictor effect of phenylephrine by a process that involves
      induction of iNOS in nonendothelial cells of the aorta. We suggest that long-term
      estrogen therapy may induce a partial hyporesponsiveness in vascular smooth
      muscle via a small but sustained nitric oxide production.

PMID- 9530197
TI  - Induction and maintenance of increased VEGF protein by chronic motor nerve
      stimulation in skeletal muscle.
AB  - Vascular endothelial growth factor (VEGF) causes endothelial cell proliferation
      in vitro and angiogenesis in vivo. Glycolytic skeletal muscles have a lower
      capillary density than oxidative muscles but can increase their capillary density
      and convert to a more oxidative phenotype when subject to chronic motor nerve
      stimulation (CMNS). We used Western analysis and immunohistochemical techniques
      to examine VEGF protein in a rabbit CMNS model of glycolytic skeletal muscle and
      in muscles with innate glycolytic versus oxidative phenotypes. VEGF protein per
      gram of total protein was increased in stimulated vs. control muscles 2.9 +/-
      1.0, 3.6 +/- 1.3, 3.1 +/- 0.5, 4.4 +/- 1.6, and 2.7 +/- 0.3 times after 3 (n =
      4), 5 (n = 2), 10 (n = 3), 21 (n = 3), and 56 (n = 2) days, respectively. VEGF
      protein was increased 3.1 +/- 0.5 times (P < 0.005) before (3, 5, and 10 days)
      and remained elevated 3.7 +/- 1.0 times (P < 0.05) after (21 and 56 days) the
      transition to an oxidative phenotype. By immunohistochemistry, VEGF protein was
      found primarily in the matrix between stimulated muscle fibers but not in the
      myocytes. In addition, VEGF protein was consistently lower in innate glycolytic
      compared with oxidative muscles. These findings suggest that VEGF plays a role in
      the alteration and maintenance of vascular density in mammalian skeletal muscles.

PMID- 9530198
TI  - Pressure-overload hypertrophy is unabated in mice devoid of AT1A receptors.
AB  - Mechanisms controlling cardiac growth are under intense investigation. Among
      these, the renin-angiotensin system has received great interest. In the current
      study, we tested the hypothesis that the renin-angiotensin system was not an
      obligate factor in cardiac hypertrophy. We examined the left ventricular
      hypertrophic response to a pressure overload in mice devoid of the AT1A receptor,
      the putative major effector of the growth response of the renin-angiotensin
      system. Aortic banding produced similar transband gradients in wild-type and AT1A
      knockout mice. The left ventricular mass-to-body weight ratio increased from 3.44
      +/- 0.08 to 5.62 +/- 0.25 in wild-type ascending aortic-banded mice. The response
      in the knockout mice was not different (from 2.97 +/- 0.13 to 5.24 +/- 0.37). We
      conclude that the magnitude of cardiac hypertrophy is not affected by the absence
      of the AT1A receptor and its signaling pathway and that this component of the
      renin-angiotensin system is not necessary in cardiac hypertrophy.

PMID- 9530199
TI  - Flow-induced arterial remodeling in rat mesenteric vasculature.
AB  - This study was designed to characterize in vivo arterial remodeling of male
      Wistar rat small mesenteric arteries exposed to varying levels of elevated blood
      flow in the presence of normal arterial pressure. Through a series of arterial
      ligations, respective ileal artery and second-order branch blood flows acutely
      increased approximately 36 and approximately 170% over basal levels. Their
      respective diameters increased 12 and 38% and their wall area increased 58 and
      120% in a time-dependent fashion between 1 and 7 days postlitigation compared
      with same-animal control vessels. Medical extracellular connective tissue
      increased concomitantly with medical wall hypertrophy. Immunostaining for
      proliferating cell nuclear antigen and nuclear profile analyses suggests that
      both smooth muscle and endothelial cell hyperplasia contribute to flow-induced
      vascular remodeling. The initial stimulus in this model is flow-mediated shear
      stress, with possible augmentation by hoop stress, which is increased
      approximately 7% by the resultant vasodilation. Stable wall thickness-to-lumen
      diameter ratios at 1, 3, and 7 days, however, suggest chronic hoop stress is
      tightly regulated and remains constant. The model described herein allows
      analyses of two arteries with different degrees of flow elevation within the same
      animal and demonstrates that the magnitude of vessel remodeling in vivo is
      directly dependent on the duration of flow elevation after abrupt arterial
      occlusion.

PMID- 9530200
TI  - Effect of tumor necrosis factor-alpha and interleukin-1 alpha on heme oxygenase-1
      expression in human endothelial cells.
AB  - Heme iron exacerbates oxidant damage by catalyzing the production of free
      radicals. Heme oxygenase is the rate-limiting enzyme involved in heme catabolism.
      An inducible form of heme oxygenase, heme oxygenase-1 (HO-1), is upregulated in
      oxidant and inflammatory settings, and recent work suggests that HO-1 induction
      may serve a protective function against oxidant injury. The ability of the
      endogenous inflammatory mediators, interleukin (IL)-1 alpha, tumor necrosis
      factor-alpha (TNF-alpha), and IL-6, to enhance HO-1 expression in cultured human
      endothelial cells was examined in this study. HO-1 mRNA and protein expression
      were upregulated by IL-1 alpha and TNF-alpha exposure but not by IL-6. Induction
      of HO-1 mRNA by IL-1 alpha and TNF-alpha occurred in a concentration- and time
      dependent fashion, with maximal expression occurring by 4 h for both cytokines.
      Induction depended on protein synthesis and occurred at the transcriptional
      level. Inhibition of the AP-1 transcription factor with curcumin decreased the
      cytokine induction of HO-1 mRNA, suggesting the involvement of this transcription
      factor in cytokine signaling of HO-1. The results of this study indicate that the
      endogenous inflammatory cytokines IL-1 alpha and TNF-alpha induce HO-1 in
      endothelial cells, providing further evidence that HO-1 may be an important
      cellular response to inflammatory stress.

PMID- 9530201
TI  - Inhibition of rat ventricular IK1 with antisense oligonucleotides targeted to
      Kir2.1 mRNA.
AB  - The cardiac inward rectifying K+ current (IK1) is important in maintaining the
      maximum diastolic potential. We used antisense oligonucleotides to determine the
      role of Kir2.1 channel proteins in the genesis of native rat ventricular IK1. A
      combination of two antisense phosphorothioate oligonucleotides inhibited
      heterologously expressed Kir2.1 currents in Xenopus oocytes, either when
      coinjected with Kir2.1 cRNA or when applied in the incubation medium. Specificity
      was demonstrated by the lack of inhibition of Kir2.2 and Kir2.3 currents in
      oocytes. In rat ventricular myocytes (4-5 days culture), these oligonucleotides
      caused a significant reduction of whole cell IK1 (without reducing the transient
      outward K+ current or the L-type Ca2+ current). Cell-attached patches
      demonstrated the occurrence of multiple channel events in control myocytes (8,
      14, 21, 35, 43, and 80 pS). The 21-pS channel was specifically knocked down in
      antisense-treated myocytes (fewer patches contained this channel, and its open
      frequency was reduced). These results demonstrate that the Kir2.1 gene encodes a
      specific native 21-pS K(+)-channel protein and that this channel has an essential
      role in the genesis of cardiac IK1.

PMID- 9530202
TI  - Effect of barodenervation on c-Fos expression in the medulla induced by static
      muscle contraction in cats.
AB  - A previous study has shown increased Fos-like immunoreactivity (FLI), a marker of
      neural activation, in the nucleus of the solitary tract (NTS) and the
      ventrolateral medulla (VLM) after static muscle contraction elicited by
      electrical stimulation of L7 and S1 ventral roots of the spinal cord in
      anesthetized, baroreceptor-intact cats. Because the electrically induced static
      muscle contraction reflexly increased arterial blood pressure, the concomitant
      activation of the arterial baroreceptor reflex during static muscle contraction
      may have resulted in some of the FLI labeling that was observed in the medulla.
      The purpose of this study was to determine regions in the medulla that are
      activated by muscle contraction in the absence of arterial baroreceptor input.
      Electrical stimulation of L7 and S1 ventral roots of the spinal cord was used to
      elicit static muscle contraction, and FLI in the medulla was determined in
      barointact and barodenervated cats. In barointact contraction cats, FLI was
      observed in the lateral reticular nucleus (LRN), NTS, lateral tegmental field
      (FTL), subretrofacial nucleus (SRF), and A1 region of the medulla. In
      barodenervated contraction cats, FLI increased in the same regions; however, the
      number of FLI-labeled cells in the NTS, FTL, and A1 region was significantly less
      than in barointact contraction animals. No significant difference in the number
      of FLI-labeled cells was found in the LRN and SRF between the two groups. These
      results clearly demonstrate that cardiovascular regions in the medulla are
      activated by input from afferent activity originating in skeletal muscle
      independently of concomitant arterial baroreceptor reflex activation.

PMID- 9530203
TI  - TAN-67, a delta 1-opioid receptor agonist, reduces infarct size via activation of
      Gi/o proteins and KATP channels.
AB  - We have previously shown that delta (delta)-opioid receptors, most notably delta
      1, are involved in the cardioprotective effect of ischemic preconditioning (PC)
      in rats; however, the mechanism by which delta-opioid receptor-induced
      cardioprotection is mediated remains unknown. Therefore, we hypothesized that
      several of the known mediators of ischemic PC such as the ATP-sensitive potassium
      (KATP) channel and Gi/o proteins are involved in the cardioprotective effect
      produced by delta 1-opioid receptor activation. To address these possibilities,
      anesthetized, open-chest Wistar rats were randomly assigned to five groups.
      Control animals were subjected to 30 min of coronary artery occlusion and 2 h of
      reperfusion. To demonstrate that stimulating delta 1-opioid receptors produces
      cardioprotection, TAN-67, a new selective delta 1-agonist, was infused for 15 min
      before the long occlusion and reperfusion periods. In addition, one group
      received 7-benzylidenenaltrexone (BNTX), a selective delta 1-antagonist, before
      TAN-67. To study the involvement of KATP channels or Gi/o proteins in delta 1
      opioid receptor-induced cardioprotection, glibenclamide (Glib), a KATP channel
      antagonist, or pertussis toxin (PTX), an inhibitor of Gi/o proteins, was
      administered before TAN-67. Infarct size (IS) as a percentage of the area at risk
      (IS/AAR) was determined by tetrazolium stain. TAN-67 significantly reduced IS/AAR
      as compared with control (56 +/- 2 to 27 +/- 5%, n = 5, P < 0.05). The
      cardioprotective effect of TAN-67 was completely abolished by BNTX, Glib, and PTX
      (51 +/- 3, 53 +/- 5, and 61 +/- 4%, n = 6 for each group, respectively). These
      results are the first to suggest that stimulating the delta 1-opioid receptor
      elicits a cardioprotective effect that is mediated via Gi/o proteins and KATP
      channels in the intact rat heart.

PMID- 9530204
TI  - Sympathetic innervation modulates repolarizing K+ currents in rat epicardial
      myocytes.
AB  - During postnatal development, sympathetic innervation of the heart evolves, and
      repolarization accelerates. Our goal in this study was to test whether
      sympathetic innervation modulates the ion channels that regulate repolarization.
      We studied action potentials and repolarizing K+ currents in epicardial myocytes
      from rats in which sympathetic innervation was accelerated or delayed,
      respectively, by subcutaneous injection of nerve growth factor (NGF) or NGF
      antibody (Ab) for the first 15 days of life. A placebo group was included as
      well. Action potential duration (APD) to 90% repolarization was greater in the Ab
      (158 +/- 18 ms)-treated than the NGF (106 +/- 10 ms)-treated animals (P < 0.05);
      the APD at 90% repolarization for the placebo group was intermediate (125 +/- 30
      ms). The transient outward (Ito) and inward rectifier (IK1) K+ currents were
      recorded in freshly dissociated cells using the whole cell patch-clamp technique.
      Ito was decreased in density at potentials positive to +40 mV in Ab-treated rats
      when compared with rats treated with NGF (P < 0.05). In addition, the
      inactivation curve of Ito in Ab-treated rats was shifted 13 mV positive to that
      of NGF-treated rats. IK1 also decreased in the Ab-treated group compared with the
      NGF group in the potential ranges of -100 to -90 mV (P < 0.05). However, the
      channel transcript abundance (RNA) in NGF-, Ab-, or placebo-treated rat hearts
      did not differ. Our results suggest that sympathetic innervation contributes to
      the developmental differences in K+ currents and APD postnatally in the rat.

PMID- 9530205
TI  - Heterogeneous fatty acid uptake early after reperfusion in rat hearts.
AB  - We determined whether spatial distributions of substrate uptake are heterogeneous
      within the area at risk during reperfusion. Quantitative autoradiography with
      imaging plates and two long-lived radioisotopes was applied to 15 open-chest,
      anesthetized rats subjected to 30 min of coronary artery ligation and 30 min of
      reperfusion. Regions showing increased beta-methyl-[1-14C]heptadecanoic acid
      ([14C]BMHDA) uptake (166 +/- 17% of that in the nonischemic area) appeared at the
      lateral borders and subepicardial layer within the area at risk, and 2-deoxy-D-[1
      3H]glucose ([3H]DG) uptake was 103 +/- 24% in these regions. Regions with
      decreased [14C]BMHDA uptake (28 +/- 11%) occupied the midmyocardial layer except
      at the lateral borders within the area at risk, and [3H]DG uptake was 62 +/- 18%
      in these regions. The percentage interregional coefficients of variation (index
      of heterogeneity) in [14C]BMHDA uptake, [3H]DG uptake, and blood flow were higher
      in the area at risk than in the nonischemic area (76 +/- 23 vs. 21 +/- 7%, 39 +/-
      10 vs. 21 +/- 7%, and 49 +/- 19 vs. 14 +/- 4%, respectively). Heterogeneous
      distributions of substrate uptake may explain the conflicting results concerning
      substrate metabolism during reperfusion.

PMID- 9530207
TI  - Effects of hypoproteinemia-induced myocardial edema on left ventricular function.
AB  - In previous studies, we observed left ventricular (LV) systolic and diastolic
      dysfunction in association with interstitial myocardial edema (IME) induced by
      either coronary venous hypertension (CVH) or lymphatic obstruction. In the
      present study, we examined the effects of myocardial edema induced by acute
      hypoproteinemia (HP) on LV systolic and diastolic function. We also combined the
      methods of HP and CVH (HP-CVH) to determine their combined effects on LV function
      and myocardial water content (MWC). We used a cell-saving device to lower plasma
      protein concentration in HP and HP-CVH groups. CVH was induced by inflating the
      balloon in the coronary sinus. Six control dogs were treated to sham HP.
      Conductance and micromanometer catheters were used to assess LV function.
      Contractility, as measured by preload recruitable stroke work, did not change in
      control or HP groups but declined significantly (14.5%) in the HP-CVH group. The
      time constant of isovolumic LV pressure decline (tau) increased significantly
      from baseline by 3 h in the HP (24.8%) and HP-CVH (27.1%) groups. The end
      diastolic pressure-volume relationship (stiffness) also increased significantly
      from baseline by 3 h in the HP (78.6%) and HP-CVH (42.6%) groups. Total plasma
      protein concentration decreased from 5.2 +/- 0.2 g/dl at baseline to 2.5 +/- 0.0
      g/dl by 3 h in the HP and HP-CVH groups. MWC of the HP (79.8 +/- 0.25%) and HP
      CVH groups (79.8 +/- 0.2%) were significantly greater than that of the control
      group (77.8 +/- 0.3%) but not different from one another. In conclusion,
      hypoproteinemia-induced myocardial edema was associated with diastolic LV
      dysfunction but not systolic dysfunction. The edema caused by hypoproteinemia was
      more than twice that produced by our previous models, yet it was not associated
      with systolic dysfunction. CVH had a negative inotropic effect and no significant
      influence on MWC. IME may not have the inverse causal relationship with LV
      contractility that has been previously postulated but appears to have a direct
      causal association with diastolic stiffness as has been previously demonstrated.

PMID- 9530206
TI  - Angiogenic potential of perivascularly delivered aFGF in a porcine model of
      chronic myocardial ischemia.
AB  - A number of heparin-binding growth factors, including basic (bFGF) and acidic
      (aFGF) fibroblast growth factors have been shown to promote angiogenesis in vivo.
      In this study, we employed a sustained-release polymer extravascular delivery
      system to evaluate the angiogenic efficacy of a novel form of genetically
      modified aFGF in the setting of chronic myocardial ischemia. Fifteen Yorkshire
      pigs subjected to Ameroid occluder placement on the left circumflex (LCX) artery
      were treated with perivascularly administered aFGF in ethylene vinyl acetate
      (EVAc) polymer (10 micrograms, n = 7) or EVAc alone (controls, n = 8). Seven to
      nine weeks later, after coronary angiography to document Ameroid-induced coronary
      occlusion, all animals underwent studies of coronary flow and global and regional
      left ventricular function. Microsphere-determined coronary flow in the Ameroid
      compromised territory was significantly increased in aFGF-treated compared with
      control animals, and this improvement in perfusion was maintained during
      ventricular pacing. Left ventricular function studies demonstrated improved
      global and regional function in aFGF-treated animals. We conclude that local
      perivascular delivery of genetically modified aFGF results in significant
      improvement in myocardial flow and regional and global left ventricular function.

PMID- 9530208
TI  - Left ventricular diastolic function of remodeled myocardium in dogs with pacing
      induced heart failure.
AB  - In patients with heart failure, decreased contractility resulting in high end
      diastolic pressures and a restrictive pattern of left ventricular filling
      produces a decrease in early diastolic filling, suggesting a stiff ventricle.
      This study investigated the elastic properties of the myocardium and left
      ventricular chamber and the ability of the heart to utilize elastic recoil to
      facilitate filling during pacing-induced heart failure in the anesthetized dog.
      Elastic properties of the myocardium were determined by analyzing the myocardial
      stress-strain relation. Left ventricular chamber properties were determined by
      analyzing the pressure-volume relation using a logarithmic approach. Elastic
      recoil was characterized using a computer-controlled mitral valve occluder to
      prevent transmittral flow during diastole. We conclude that, during heart
      failure, the high end-diastolic pressures suggestive of a stiff ventricle are due
      not to stiffer myocardium but to a ventricle whose chamber compliance
      characteristics are changed due to geometric remodeling of the myocardium. The
      restrictive filling pattern is a result of the ventricle being forced to operate
      on the stiff portion of the diastolic pressure-volume relation to maintain
      cardiac output. Slowed relaxation and decreased contractility result in an
      inability of the heart to contract to an end-systolic volume below its diastolic
      equilibrium volume. Thus the left ventricle cannot utilize elastic recoil to
      facilitate filling during heart failure.

PMID- 9530209
TI  - Stretch-induced protection shares a common mechanism with ischemic
      preconditioning in rabbit heart.
AB  - We sought to determine whether stretch-induced preconditioning may be related to
      activation of adenosine receptors, ATP-sensitive K+ (K+ATP) channels, and/or
      protein kinase C (PKC) in the rabbit heart. Anesthetized rabbits underwent 30 min
      of coronary artery occlusion followed by 3 h of reperfusion. Ischemic
      preconditioning was induced by one episode of 5 min of ischemia followed by 5 min
      of reperfusion, and stretch preconditioning was induced by a transient volume
      overload. The abilities of gadolinium (Gd3+), a blocker of stretch-activated
      channels, glibenclamide (Glib), a blocker of K+ATP channels, 8-(p-sulfophenyl)
      theophylline (8-SPT), a blocker of adenosine receptors, and polymyxin B (PMXB),
      an antagonist of PKC, to prevent the infarct size-limiting effect of stretch
      induced preconditioning were evaluated. Because the infarct size-reducing effect
      of stretch occurred in the absence of ischemia and was prevented by previous
      administration of Gd3+, Glib, 8-SPT, and PMXB, we propose that activation of
      mechanosensitive ion channels protects the rabbit heart from subsequent sustained
      ischemic insult, likely through a mechanism that involves downstream activation
      of PKC, adenosine receptors, and/or K+ATP channels.

PMID- 9530210
TI  - Induction of HSP 32 gene in hypoxic cardiomyocytes is attenuated by treatment
      with N-acetyl-L-cysteine.
AB  - Increased synthesis of stress proteins may enhance myocardial viability during
      periods of low oxygen delivery. Our purpose was to determine if the oxidative
      stress protein heme oxygenase-1 [heat stress protein 32 (HSP 32)] was induced in
      hypoxic cardiomyocytes and whether this induction might be mediated by a redox
      sensitive mechanism. Primary rat neonatal cardiomyocytes, cultured to express a
      tissuelike phenotype, responded to 12 h of hypoxia (< 0.5% ambient oxygen) with
      an approximately fivefold (range 3- to 7.5-fold; P < 0.05) increase in HSP 32
      mRNA and a threefold (P < 0.05) increase in HSP 32 protein content. Exposure to
      80 microM H2O2 for 3 h increased HSP 32 mRNA content to a similar extent.
      Expression of heme oxygenase-2 mRNA was unaffected by H2O2 or hypoxic treatments.
      Inclusion of 20 mM N-acetyl-L-cysteine in the medium during hypoxia reduced the
      increase in HSP 32 mRNA and protein expression by 25.50% compared with hypoxia
      alone. The data suggest that induction of HSP 32 protein may lead to an improved
      antioxidant defense in cardiomyocytes during hypoxia and that a redox-sensitive
      pathway mediates at least a portion of the hypoxic induction of the HSP 32 gene.

PMID- 9530211
TI  - Cerebral arteriolar dilations by KATP channel activators need L-lysine or L
      arginine.
AB  - We investigated the effects of various amino acids on responses to ATP-sensitive
      potassium (KATP) channel openers in anesthetized cats equipped with cranial
      windows. The application of pinacidil by superfusion caused transient
      vasodilation, whereas there was sustained vasodilation from the application of
      stationary solution of pinacidil. In the presence of L-arginine or L-lysine,
      pinacidil by superfusion led to sustained vasodilation, suggesting that the rapid
      flow of fluid displaced these amino acids from binding on the channel and that
      such binding was essential for opening the channel. NG-nitro-L-arginine blocked
      responses to pinacidil, and this blockade was reversed by L-lysine or L-arginine
      but not by D-arginine, D-lysine, methyl-L-arginine, glycine, L-histidine,
      dimethylarginine, dimethyl-L-arginine, or hydroxylysine. The blockade of
      responses to pinacidil induced by glyburide was also reversed completely by L
      arginine or L-lysine but not by D-arginine, suggesting that these amino acids act
      on the sulfonylurea receptor. Hydroxylysine but not methyl-L-lysine,
      dimethylarginine, or dimethyl-L-arginine blocked responses to pinacidil. The
      findings show that KATP channels in cerebral arterioles need L-lysine or L
      arginine to open in response to agonists.

PMID- 9530212
TI  - Nitric oxide from neuronal NOS plays critical role in cerebral capillary flow
      response to hypoxia.
AB  - We investigated, using a direct, intravital microscopic technique, whether nitric
      oxide (NO) from neuronal nitric oxide synthase (nNOS) plays a role in the
      cerebral capillary flow response to acute hypoxia. Erythrocyte flow in subsurface
      capillaries of the frontoparietal cortex of adult Sprague-Dawley rats was
      visualized using epifluorescence videomicroscopy after fluorescent labeling of
      red blood cells (RBC) in tracer concentrations. The velocity of labeled RBC in
      individual capillaries was measured off-line using an image analysis system.
      Hypoxia was produced by lowering the inspired O2 concentration to 15% for 5 min
      in control animals and in those pretreated with the selective nNOS inhibitor 7
      nitroindazole (7-NI; 20 mg/kg ip). In the control group, hypoxia increased RBC
      velocity by 34 +/- 8%. In the group treated with 7-NI, this response was reversed
      to a statistically significant 8 +/- 3% decrease. This paradoxical response to
      hypoxia after 7-NI was observed in nearly all capillaries. 7-NI itself decreased
      the baseline RBC velocity by 12 +/- 4%. The cerebral hyperemic response to
      hypoxia was also assessed with the laser Doppler flow (LDF) technique. In control
      animals, hypoxia produced a 33 +/- 6% increase in LDF, similar to the increase in
      RBC velocity. After 7-NI treatment, the response to hypoxia was moderately
      attenuated but still significant at a 19 +/- 2% increase in LDF. These results
      support the role of NO from nNOS in the cerebral hyperemic response to hypoxia.
      They imply that 7-NI interfered with a physiological mechanism that was
      fundamental to cerebral capillary flow regulation and provide direct evidence
      that cerebral capillary perfusion may be dissociated from a concurrent change in
      regional tissue perfusion as reflected by LDF. In conclusion, NO from nNOS
      contributes to the maintenance of RBC flow in cerebral capillaries and plays a
      critically important role in the selective regulation of cerebral capillary flow
      during hypoxia.

PMID- 9530213
TI  - Effect of ventricular stretch on contractile strength, calcium transient, and
      cAMP in intact canine hearts.
AB  - Isovolumic contractions were imposed by intraventricular balloon in 39 isolated,
      blood-perfused canine hearts to investigate the effects of myocardial stretch on
      contractile force. After stabilization at 37 degrees C, left ventricular volume
      was increased so that end-diastolic pressure increased from 0 to 5 mmHg. After
      the immediate increase in developed pressure [DP; from 37 +/- 14 to 82 +/- 22
      mmHg (means +/- SD)], there was a slow secondary rise in DP (97 +/- 27 mmHg) that
      peaked at 3 min. However, DP subsequently decreased over the next 7 min back to
      the initial value (84 +/- 25 mmHg). Light emission from microinjected aequorin (n
      = 10 hearts) showed that changes in intracellular calcium [3 min: 124 +/- 15% (P
      < 0.01); 10 min: 99 +/- 18% of baseline] paralleled DP changes. Increases in
      myocardial adenosine 3',5'-cyclic monophosphate (cAMP) content (n = 12)
      accompanied the secondary rise in DP. In contrast, the gradual elevation of DP
      after the stretch was not exerted during continuous beta-adrenergic stimulation
      by isoproterenol. Thus, in contrast to isolated muscle, stretch only transiently
      increases intracellular calcium and contractile strength in intact hearts. The
      findings of changes in cAMP and abolition of the phenomena by beta-stimulation
      suggest that a primary stretch-mediated influence on cAMP metabolism may underlie
      these phenomena.

PMID- 9530214
TI  - Peroxynitrite-mediated vasorelaxation: evidence against the formation of
      circulating S-nitrosothiols.
AB  - Peroxynitrite-induced relaxation of isolated vessels may involve the formation of
      S-nitrosothiols. This study characterized the hemodynamic effects of systemically
      injected peroxynitrite in penotobarbital sodium-anesthetized rats and determined
      whether these effects were due to the formation of S-nitrosothiols. We utilized L
      penicillamine, which attenuates the hemodynamic effects of systemically injected
      S-nitrosothiols. The hemodynamic effects of peroxynitrite and the S-nitrosothiols
      L-S-nitrosocysteine, L-S-nitrosoglutathione, and S-nitrosoalbumin were determined
      before and 25 min after the administration of L-penicillamine or saline.
      Peroxynitrite and the S-nitrosothiols produced dose-dependent reductions in mean
      arterial pressure and mesenteric and hindquarter vascular resistances. The
      hypotensive and vasodilator effects of the S-nitrosothiols were significantly
      reduced by L-penicillamine. In contrast, the hemodynamic actions of peroxynitrite
      were unaffected by L-penicillamine. Therefore, peroxynitrite produces hypotensive
      and vasodilator responses in anesthetized rats that are unlikely to be due to the
      formation of circulating S-nitrosothiols. The mechanisms by which peroxynitrite
      produces vasodilatation in vivo remain to be determined.

PMID- 9530215
TI  - Mechanisms of cell injury in rat mesentery and cremaster muscle.
AB  - The events responsible for cell injury after a tissue stimulation are only
      incompletely understood. The purpose of this study was to examine mechanisms of
      cell injury in two tissues, rat mesentery and cremaster muscle, after tissue
      stimulation with N-formylmethionyl-leucyl-phenylalanine (FMLP) and platelet
      activating factor (PAF). The response was studied in the same animal in random
      order using normal and leukopenic rats. The tissues were exteriorized after
      pentobarbital anesthesia. Five to six vascularized areas were chosen in each
      tissue, and cell injury and hydroperoxide production were assessed visually by
      continuous superfusion with 1 microM propidium iodide and 5 microM
      dichlorofluorescin diacetate (DCFH), respectively. FMLP (1 x 10(-8) M) and then
      PAF (1 x 10(-8) M) were added to the superfusate, and measurements were made at
      several time points. The second tissue was then examined using the same protocol.
      In the cremaster, there was little hydroperoxide production, and the tissue
      injury was eliminated after leukopenia. Leukopenia had no effect on tissue injury
      in the mesentery. Although hydroperoxide production was observed, there was no
      correlation between it and the tissue injury. The level of preactivation showed
      no correlation with either tissue injury or hydroperoxide production. In light of
      these results, mast cell degranulation may be an important mechanism of tissue
      injury in the mesentery.

PMID- 9530216
TI  - A model for red blood cell motion in glycocalyx-lined capillaries.
AB  - The interior surfaces of capillaries are lined with a layer (glycocalyx) of
      macromolecules bound or absorbed to the endothelium. Here, a theoretical model is
      used to analyze the effects of the glycocalyx on hematocrit and resistance to
      blood flow in capillaries. The glycocalyx is represented as a porous layer that
      resists penetration by red blood cells. Axisymmetric red blood cell shapes are
      assumed, and effects of cell membrane shear elasticity are included. Lubrication
      theory is used to compute the flow of plasma around the cell and within the
      glycocalyx. The effects of the glycocalyx on tube hematocrit (Fahraeus effect)
      and on flow resistance are predicted as functions of the width and hydraulic
      resistivity of the layer. A layer of width 1 micron and resistivity 10(8)
      dyn.s/cm4 leads to a relative apparent viscosity of approximately 10 in a 6
      micron capillary at discharge hematocrit 45% and flow velocity of approximately 1
      mm/s. This is consistent with experimental observations of increased flow
      resistance in microvessels in vivo, relative to glass tubes with the same
      diameters.

PMID- 9530217
TI  - Mathematical considerations for modeling cerebral blood flow autoregulation to
      systemic arterial pressure.
AB  - The shape of the autoregulation curve for cerebral blood flow (CBF) vs. pressure
      is depicted in a variety of ways to fit experimentally derived data. However,
      there is no general empirical description to reproduce CBF changes resulting from
      systemic arterial pressure variations that is consistent with the reported data.
      We analyzed previously reported experimental data used to construct
      autoregulation curves. To improve on existing portrayals of the fitting of the
      observed data, a compartmental model was developed for synthesis of the
      autoregulation curve. The resistive arterial and arteriolar network was
      simplified as an autoregulation device (ARD), which consists of four compartments
      in series controlling CBF. Each compartment consists of a group of identical
      vessels in parallel. The response of each vessel category to changes in perfusion
      pressure was simulated using reported experimental data. The CBF-pressure curve
      was calculated from the resistance of the ARD. The predicted autoregulation curve
      was consistent with reported experimental data. The lower and upper limits of
      autoregulation (LLA and ULA) were predicted as 69 and 153 mmHg, respectively. The
      average value of the slope of the CBF-pressure curve below LLA and beyond ULA was
      predicted as 1.3 and 3.3% change in CBF per mmHg, respectively. Our four
      compartment ARD model, which simulated small arteries and arterioles, predicted
      an autoregulation function similar to experimental data with respect to the LLA,
      ULA, and average slopes of the autoregulation curve below LLA and above ULA.

PMID- 9530218
TI  - Mechanisms of length history-dependent tension in an ionic model of the cardiac
      myocyte.
AB  - The ionic model of the ventricular myocyte developed by Luo and Rudy (Circ. Res.
      74: 1071-1096, 1994) was used to investigate potential mechanisms of the slow
      changes in stress (SCS) that follow step changes in muscle length. A step change
      in myofilament sensitivity alone caused an immediate increase in active tension,
      but no SCS. The effects of additional step changes in the parameters of
      sarcolemmal ion fluxes were examined for each ion flux in the model. Changes in
      the coefficients of Ca2+ or K+ channels did not produce SCS. SCS was produced by
      step changes in parameters of the Na(+)-K+ pump or the Na+ leak current. This
      simulated mechanism was mediated through a slow increase in intracellular Na+
      concentration and a resulting increase in systolic Ca2+ entry through the
      Na+/Ca2+ exchanger. The model reproduced the effects of several experimental
      interventions such as sarcoplasmic reticulum Ca2+ depletion, "diastolic" length
      changes, and changes in extracellular Ca2+. Thus SCS in cardiac muscle may be
      caused by length-induced changes in sarcolemmal Na+ fluxes.

PMID- 9530219
TI  - Application of HPLC to counting of colored microspheres in determination of
      regional blood flow.
AB  - Colored microspheres have become popular compared with radioactive microspheres
      because they do not use radioactivity. However, they suffer from a much greater
      variability in their determination. We have developed a new method for assaying
      the dye using high-performance liquid chromatography (HPLC) with internal
      standard. This technique permits accurate determination of < or = 400 spheres in
      rat blood, heart, kidney, liver, and brain with a relative error [coefficient of
      variation (CV)] < 10%. To date, only three colors (white, yellow, and red) may be
      used because, of the five colors tested, one (violet) served as internal standard
      and another (blue) exhibited marked degradation during extraction. Compared with
      the classical spectrophotometric technique, HPLC allows a three to five times
      improvement in reproducibility with a relative error significantly lower (P <
      0.01) than with direct spectrophotometry. Although this new technique appears to
      be more time consuming than the classical method, its use seems to be preferable
      because of the improvement in measurement sensitivity.

PMID- 9530220
TI  - Electrophoretic separation and quantitation of cardiac myosin heavy chain
      isoforms in eight mammalian species.
AB  - A protocol for sample preparation and gel electrophoresis is described that
      reliably results in the separation of the alpha- and beta-isoforms of cardiac
      myosin heavy chain (MHC-alpha and MHC-beta) in eight mammalian species. The
      protocol is based on a simple, nongradient denaturing gel. The magnitude of
      separation of MHC-alpha and MHC-beta achieved with this protocol is sufficient
      for quantitative determination of the relative amounts of these two isoforms in
      mouse, rat, guinea pig, rabbit, canine, pig, baboon, and human myocardial
      samples. The sensitivity of the protocol is sufficient for the detection of MHC
      isoforms in samples at least as small as 1 microgram. The glycerol concentration
      in the separating gel is an important factor for successfully separating MHC
      alpha and MHC-beta in myocardial samples from different species. The effect of
      sample load on MHC-alpha and MHC-beta band resolution is illustrated. The results
      also indicate that inclusion of a homogenization step during sample preparation
      increases the amount of MHC detected on the gel for cardiac samples to a much
      greater extent than for skeletal muscle samples. Although the protocol described
      in this study is excellent for analyzing cardiac samples, it should be noted that
      the same protocol is not optimal for separating MHC isoforms expressed in
      skeletal muscle, as is illustrated.

PMID- 9530221
TI  - VEGF upregulates ecNOS message, protein, and NO production in human endothelial
      cells.
AB  - Vascular endothelial growth factor (VEGF) is an endothelium-specific secreted
      protein that potently stimulates vasodilation, microvascular hyperpermeability,
      and angiogenesis. Nitric oxide (NO) is also reported to modulate vascular tone,
      permeability, and capillary growth. Therefore, we hypothesized that VEGF might
      regulate endothelial production of NO. The production of nitrogen oxides by human
      umbilical vein endothelial cells (HUVECs) was measured after 1, 12, 24, and 48 h
      of incubation with VEGF. VEGF treatment resulted in both an acute (1 h) and
      chronic (> 24 h) stimulation of NO production. Furthermore, Western and Northern
      blotting revealed a VEGF-elicited, dose-dependent increase in the cellular
      content of endothelial cell nitric oxide synthase (ecNOS) message and protein
      that may account for the chronic upregulation of NO production elicited by VEGF.
      Finally, endothelial cells pretreated with VEGF for 24 h and subsequently exposed
      to A-23187 for 1 h produced NO at approximately twice the rate of cells that were
      not pretreated with VEGF. We conclude that VEGF upregulates ecNOS enzyme and
      elicits a biphasic stimulation of endothelial NO production.

PMID- 9530222
TI  - Tumor necrosis factor in the heart.
AB  - The heart is a tumor necrosis factor (TNF)-producing organ. Both myocardial
      macrophages and cardiac myocytes themselves synthesize TNF. Accumulating evidence
      indicates that myocardial TNF is an autocrine contributor to myocardial
      dysfunction and cardiomyocyte death in ischemia-reperfusion injury, sepsis,
      chronic heart failure, viral myocarditis, and cardiac allograft rejection.
      Indeed, locally (vs. systemically) produced TNF contributes to postischemic
      myocardial dysfunction via direct depression of contractility and induction of
      myocyte apoptosis. Lipopolysaccharide or ischemia-reperfusion activates
      myocardial P38 mitogen-activated protein (MAP) kinase and nuclear factor kappa B,
      which lead to TNF production. TNF depresses myocardial function by nitric oxide
      (NO)-dependent and NO-independent (sphingosine dependent) mechanisms. TNF
      activation of TNF receptor 1 or Fas may induce cardiac myocyte apoptosis. MAP
      kinases and TNF transcription factors are feasible targets for anti-TNF (i.e.,
      cardioprotective) strategies. Endogenous anti-inflammatory ligands, which trigger
      the gp130 signaling cascade, heat shock proteins, and TNF-binding proteins, also
      control TNF production and activity. Thus modulation of TNF in cardiovascular
      disease represents a realistic goal for clinical medicine.

PMID- 9530223
TI  - Effect of intravenous glucose and euglycemic insulin infusions on short-term
      appetite and food intake.
AB  - To investigate the short-term effects of insulin on feeding, 14 fasting, young
      adults received 150-min euglycemic intravenous infusions of control (C), low-dose
      (LD, 0.8 mU.kg-1.min-1), and high-dose (HD, 1.6 mU.kg-1.min-1) insulin and ate
      freely from a buffet meal during the last 30 min. Steady-state preprandial plasma
      insulin concentrations were 5.9 +/- 0.7 (C), 47 +/- 2 (LD), and 95 +/- 6 (HD)
      microU/ml and increased 56-59 microU/ml during the meal. No effect of treatment
      type of hunger or fullness ratings, duration of eating, or the weight, energy
      content (1,053 +/- 95 kcal, C; 1,045 +/- 101 kcal, LD; 1,066 +/- 107 kcal, HD; P
      = 0.9), and composition of food eaten was observed. On a fourth study day, 12 of
      the subjects received an intravenous infusion of glucose only (Glc) that was
      identical to the glucose infusion on their HD insulin day. Mean venous glucose
      concentration was 9.3 +/- 0.5 mmol [P < 0.001 vs. C (5.3 +/- 0.1), LD (5.2 +/-
      0.2), and HD (5.2 +/- 0.2)], and plasma insulin increased to 45 +/- 2.3 microU/ml
      at the start and 242 +/- 36 microU/ml at the end of the meal. Energy intake
      during the meal was (approximately 15%) reduced (1,072 +/- 97 kcal, C; 1,086 +/-
      102 kcal, LD; 1,088 +/- 105 kcal, HD; 919 +/- 115 kcal, Glc; P < 0.05 Glc vs. C,
      LD, and HD). Plasma insulin normally increases to approximately 100 microU/ml
      after a mixed meal in lean subjects. Therefore, in the absence of altered blood
      glucose concentrations, physiological concentrations of insulin are unlikely to
      play a role in meal termination and the short-term control of appetite.

PMID- 9530224
TI  - Thermoeffector thresholds and preferred ambient temperatures of the FOK rat.
AB  - The FOK is an inbred rat strain with a genotypic adaptation to hot environments.
      The present study compared the thermoeffector thresholds and preferred ambient
      temperatures (Tpref) of the FOK rat with those of other rat strains. Male FOK,
      WKAH, and Donryu rats were used. First, they were loosely restrained and placed
      individually in a metabolic chamber with an ambient temperature of 26.0 degrees
      C. Their hypothalamic temperature (T(hy)), tail skin temperature (Tsk), and heat
      production (M) were measured. After thermal equilibrium had been attained, the
      rats were gradually warmed and then cooled using an intravenous thermode. The
      threshold T(hy) values for tail skin vasodilation and cold-induced thermogenesis
      were defined as the points at which sharp increases in Tsk and M occurred,
      respectively. The two thresholds of the FOK rat were lower than those of the WKAH
      and Donryu rats. In a second set of experiments, the FOK and WKAH rats were
      placed individually in a thermocline. Their intra-abdominal temperatures (T(ab))
      were measured by a biotelemetry system, and the rats' Tpref values were estimated
      with the thermal gradient. Mean T(ab) and Tpref over a 24-h period for the FOK
      rat were significantly lower than those of the WKAH rat. The results suggest that
      in the FOK rat the control ranges of autonomic and behavioral thermoregulation
      are lower than those of the other rat strains examined. This contributes to the
      maintenance of core temperature at low levels.

PMID- 9530225
TI  - Temporal relationships between eating behavior and liver adenine nucleotides in
      rats treated with 2,5-AM.
AB  - Administration of the fructose analog 2,5-anhydro-D-mannitol (2,5-AM) elicits
      eating behavior in rats by its action in the liver. To evaluate whether the
      decrease in liver ATP levels produced by injection of 2,5-AM plays a role in the
      eating response, we examined the relationship between changes in eating behavior
      and liver adenine nucleotide levels over time in rats given 2,5-AM. Liver ATP
      concentrations decreased within 15 min after injection of 2,5-AM (300 mg/kg ip),
      remained low for up to 90 min postinjection, and returned to control (saline
      injection) levels by 4 h after treatment. Rats fed ad libitum initiated eating
      between 15 and 45 min after 2,5-AM treatment, after liver ATP levels had
      declined. Rats given food 1 h after 2,5-AM treatment increased food intake, but
      if access to food was delayed for 4 h after 2,5-AM injection the eating response
      was attenuated or absent. Whereas liver AMP and ADP levels were also altered by
      injection of 2,5-AM, changes in food intake did not consistently track changes in
      these nucleotides. The results support the hypothesis that the eating response to
      2,5-AM is triggered by a decrease in liver ATP level.

PMID- 9530226
TI  - Disordered food intake and obesity in rats lacking cholecystokinin A receptors.
AB  - Otsuka Long-Evans Tokushima Fatty (OLETF) rats develop obesity, hyperglycemia,
      and non-insulin-dependent diabetes mellitus and do not express cholecystokinin A
      (CCK-A) receptors, the receptor subtype mediating the satiety actions of CCK. In
      short-term feeding tests, male OLETF rats were completely resistant to exogenous
      CCK, and their response to bombesin was attenuated. Comparisons of liquid meal
      consumption in OLETF and control Long-Evans Tokushima (LETO) rats demonstrated
      that 1) OLETF rats had greater intakes during 30-min scheduled daytime meals and
      significantly larger and fewer spontaneous night-time meals and 2) although the
      initial rates of licking were the same, OLETF rats maintained the initial rate
      longer and the rate at which their licking declined was slower. In 24-h solid
      food access tests, OLETF rats consumed significantly more pellets than LETO
      controls, and this increase was attributable to significant increases in meal
      size. Together, these data are consistent with the interpretation that the lack
      of CCK-A receptors in OLETF rats results in a satiety deficit leading to
      increases in meal size, overall hyperphagia, and obesity.

PMID- 9530227
TI  - Determinants of cardiac tyrosine hydroxylase activity during exercise-induced
      sympathetic activation in humans.
AB  - This study assessed whether the mechanisms regulating cardiac norepinephrine (NE)
      synthesis with changes in NE release are influenced by functions of sympathetic
      nerves affecting transmitter turnover independently of transmitter release.
      Differences in arterial and coronary venous plasma concentrations of NE and its
      metabolites and of dihydroxyphenylalanine (DOPA), the immediate product of
      tyrosine hydroxylase (TH), were examined before and during cycling exercise.
      Relative increases during exercise in cardiac tyrosine hydroxylation (as
      reflected by the %increase in cardiac DOPA spillover) matched closely
      corresponding increases in NE turnover, but were much lower than increases in NE
      release. The much larger relative increases in release than turnover of NE were
      largely attributable to the extensive contribution to transmitter turnover from
      intraneuronal metabolism of NE leaking from storage vesicles. This contribution
      remains unchanged during sympathetic activation so that the relative increase in
      NE turnover is much smaller than that in exocytotic release of NE. To replenish
      the NE lost from stores during sympathetic activation, TH activity need increase
      only in proportion to the smaller increase in turnover rather than the larger
      relative increase in release. The ability to "gear down" increases in tyrosine
      hydroxylation relative to increases in NE release provides sympathetic nerves the
      capacity for a more extended range of sustainable release rates than otherwise
      possible.

PMID- 9530228
TI  - Benzamil blockade of brain Na+ channels averts Na(+)-induced hypertension in
      rats.
AB  - To determine the possible involvement of brain amiloride-sensitive Na+ channels
      in Na(+)-induced hypertension, we investigated the effects of benzamil
      hydrochloride, a specific blocker of these Na+ channels, on the acute pressor
      mechanisms of intracerebroventricular infusion of hypertonic NaCl and the
      continuous pressor mechanisms of Na(+)-induced chronic hypertension, such as
      deoxycorticosterone acetate-salt hypertensive or stroke-prone spontaneous
      hypertensive rats, and of non-Na(+)-induced hypertension, such as renovascular
      hypertensive rats. Intracerebroventricular preinjection with benzamil (1 or 10
      nmol/kg) abolished the increase in mean arterial pressure, heart rate, abdominal
      sympathetic discharge, and plasma vasopressin concentration induced by an acute
      increase in cerebrospinal Na+ concentrations at intracerebroventricular infusion
      of 1.5 M hypertonic NaCl. Continuous intracerebroventricular infusion of benzamil
      (1 or 10 nmol.kg-1.day-1) for 7 days attenuated Na(+)-induced chronic
      hypertension in both deoxycorticosterone acetate-salt and stroke-prone
      spontaneous hypertensive rats, accompanied by reduction of urinary excretion of
      vasopressin and norepinephrine but not in renovascular hypertensive rats.
      Intravenous infusion of benzamil (10 nmol.kg-1.day-1) for 7 days affected neither
      arterial pressure nor urinary excretion of vasopressin and norepinephrine in
      either model of hypertension. Benzamil-blockable brain amiloride-sensitive Na+
      channels are expected to function as one of the Na+ receptors in the brain and to
      be involved in the pressor mechanism of Na(+)-induced hypertension.

PMID- 9530229
TI  - Elevation of brain 5-HT activity, POMC expression, and plasma cortisol in
      socially subordinate rainbow trout.
AB  - Agonistic behavior, brain concentrations of serotonin (5-hydroxytryptamine, 5
      HT), and 5-hydroxyindoleacetic acid (5-HIAA, the main 5-HT metabolite), plasma
      cortisol levels, and the pituitary expression of pro-opiomelanocortin (POMC) A
      and B mRNA were determined in socially dominant and subordinate rainbow trout
      after 1 or 7 days of social interaction. Telencephalic and brain stem 5-HIAA/5-HT
      ratios, plasma cortisol levels, and pituitary POMC mRNA concentrations were
      elevated in fish being subordinate for 1 day. Furthermore, neither telencephalic
      5-HIAA/5-HT ratios nor pituitary POMC A or POMC B mRNA expression showed any
      decline after 7 days of social interaction. By contrast, plasma cortisol
      concentrations of subordinate fish declined after 7 days but were still
      significantly higher than in dominant fish. Furthermore, in subordinate fish,
      hypothalamic 5-HIAA/5-HT ratios and plasma cortisol levels were highly
      correlated, suggesting an important role of hypothalamic 5-HT in the regulation
      of the teleost hypothalamic-pituitary-interrenal (HPI) axis. The number of
      aggressive acts received and plasma cortisol levels were highly correlated in 1
      day subordinates, a relationship not seen in fish subjected to 1 wk of
      subordination. Thus the chronic stress experienced by subordinates in established
      dominance hierarchies appears to be more closely related to the threat imposed by
      the presence of the dominant fish than to actual aggressive encounters. The
      sustained elevation of pituitary POMC mRNA expression, an effect mainly related
      to an increase of melanotropic POMC expression, in subordinates could be a
      mechanism serving to maintain HPI axis excitability and promote acclimation in
      these individuals.

PMID- 9530230
TI  - Effects of interleukin-1 beta on sleep are mediated by the type I receptor.
AB  - Interleukin-1 beta (IL-1 beta) is a well characterized sleep regulatory
      substance. To study receptor mechanisms for the sleep-promoting effects of IL-1
      beta, sleep patterns were determined in control and IL-1 type I receptor knockout
      (IL-1RI KO) mice with a B6x129 background after intraperitoneal injections of
      saline or murine recombinant IL-1 beta. The IL-1RI KO mice had slightly but
      significantly less sleep during the dark period compared with the controls. IL-1
      beta dose dependently increased non-rapid eye movement sleep (NREMS) and
      suppressed rapid eye movement sleep (REMS) in the controls. The IL-1RI KO mice
      did not respond to IL-1 beta. In contrast, the IL-1RI KO mice increased NREMS and
      decreased REMS after administration of tumor necrosis factor-alpha (TNF-alpha),
      another well characterized sleep-promoting substance. These results 1) provide
      further evidence that IL-1 beta is involved in sleep regulation, 2) indicate that
      the effects of IL-1 beta on sleep are mediated by the type I receptor, and 3)
      suggest that TNF-alpha is capable of inducing sleep without the involvement of IL
      1.

PMID- 9530231
TI  - Carbon dioxide transport in alligator blood and its erythrocyte permeability to
      anions and water.
AB  - Deoxygenation of alligator red blood cells (RBCs) caused binding of two HCO3-
      equivalents per hemoglobin (Hb) tetramer at physiological pH. At lowered pH, some
      HCO3- binding also occurred to oxygenated Hb. The erythrocytic total CO2 content
      was large, and Hb-bound HCO3-, free HCO3-, and carbamate contributed about
      equally in deoxygenated cells. The nonbicarbonate buffer values of RBCs and Hb
      were high, and the Hb showed a significant fixed acid Haldane effect. Binding of
      HCO3- on deoxygenation occurred without a change in RBC intracellular pH,
      revealing equivalence between oxylabile HCO3- and H+ binding. Erythrocyte volume,
      plasma pH, and plasma HCO3- concentration also varied little with the degree of
      oxygenation. Diffusional water permeability was higher in oxygenated than
      deoxygenated RBCs. The RBCs have rapid band 3-mediated Cl- and HCO3- transport,
      which was not affected by degree of oxygenation, but net fluxes of Cl- and HCO3-
      via the anion exchanger are small during blood circulation at rest. Most of the
      CO2 taken up into the blood as it flows through tissue capillaries is carried
      within the erythrocytes as Hb-bound HCO3- until CO2 is excreted when blood flows
      through pulmonary capillaries.

PMID- 9530232
TI  - Opioid peptides mediate heat stress-induced immunosuppression during pregnancy.
AB  - To clarify the involvement of the opioid system in enhanced immunosuppression
      induced by heat stress during pregnancy, we examined the effects of heat exposure
      and intraperitoneal administration of opioid receptor antagonist naloxone on beta
      endorphin (beta-EP) in blood, pituitary lobes, and placenta as well as splenic
      natural killer cell activity (NKCA) and placental steroids in pregnant rats at 15
      16 days gestation. Two-way analysis of variance revealed significant increases in
      blood beta-EP induced by heat and naloxone and a significant interaction between
      heat and naloxone on blood beta-EP and progesterone (P). Whereas heat reduced
      NKCA, intraperitoneal administration of naloxone reversed it. Significant
      increases in blood and placental beta-EP induced by both heat and naloxone
      administration and a significant interaction on blood and placental beta-EP was
      observed. These results suggest that immunosuppression produced by heat stress
      during pregnancy is mediated by the opioid system. A positive correlation between
      beta-EP in blood and placenta during heat and naloxone administration suggests
      that increased placental beta-EP during heat results in hypersecretion of beta-EP
      into blood. P increased by heat during pregnancy may be involved in the
      immunosuppression.

PMID- 9530233
TI  - K+ channel blockade in the NTS alters efficacy of two cardiorespiratory reflexes
      in vivo.
AB  - We investigated the role of potassium conductances in the nucleus of the solitary
      tract (NTS) in determining the efficacy of the baroreceptor and cardiopulmonary
      reflexes in anesthetized rats. The baroreceptor reflex was elicited with an
      intravenous injection of phenylephrine to evoke a reflex bradycardia, and the
      cardiopulmonary reflex was evoked with a right atrial injection of
      phenylbiguanide. Microinjection of two Ca-dependent potassium channel antagonists
      (apamin and charybdotoxin) into the NTS potentiated the baroreceptor reflex
      bradycardia. This may reflect the increased neuronal excitability observed
      previously in vitro with these blockers. In contrast, the Ca-dependent potassium
      channel antagonists attenuated the cardiopulmonary reflex, whereas voltage
      dependent potassium channel antagonists (4-aminopyridine and dendrotoxin)
      attenuated both the baro- and cardiopulmonary reflexes when microinjected into
      the NTS. The possibility that the reflex attenuation observed indicates a
      predominant distribution of certain potassium channels on gamma-aminobutyric acid
      interneurons is discussed.

PMID- 9530234
TI  - Circadian rhythms in diving behavior and ventilatory response to asphyxia in
      canvasback ducks.
AB  - Underwater feeding behavior was measured in 10 captive canvasback ducks (Aythya
      valisineria) for 12 days under a 12:12-h light-dark photoperiod. Feeding activity
      exhibited a daily rhythm, with 76% of dives occurring at night. In separate
      experiments on six of these ducks, a circadian rhythm was observed in the
      duration of voluntary dives. Dives at night (14.7 +/- 0.7 s) were significantly
      longer than those during the day (10.7 +/- 0.7 s). These day-night differences in
      diving behavior were accompanied by day-night differences in respiratory
      responses to progressive asphyxia. In the same six ducks, ventilation increased
      exponentially as a function of inspired CO2 concentration during rebreathing in a
      closed-circuit barometric plethysmograph. The exponential rate constant for
      inspired ventilation was significantly smaller at night (0.23 +/- 0.02) than
      during the day (0.26 +/- 0.01). We suggest that intermittent apneic exercise is
      facilitated by reduced respiratory chemosensitivity and that the respiratory and
      behavioral control systems are synchronized by the circadian timing system in
      diving ducks.

PMID- 9530235
TI  - Altered frequency characteristics of sympathetic nerve activity after sustained
      elevation in arterial pressure.
AB  - We tested the hypothesis that sustained elevation in mean arterial pressure (MAP)
      alters the frequency-domain characteristics of efferent sympathetic nerve
      discharge (SND) after the return of MAP to control levels. Renal, lumbar, and
      splanchnic SND were recorded before, during, and after a 30-min increase in MAP
      produced by phenylephrine (PE) infusion in alpha-chloralose-anesthetized,
      spontaneously hypertensive (SH) rats. The following observations were made. 1)
      The basic cardiac-locked pattern of renal, lumbar, and splanchnic SND bursts was
      altered after sustained elevation in MAP, demonstrating prolonged effects on the
      neural circuits involved in entraining efferent SND to the cardiac cycle.
      Importantly, discharge bursts in afferent baroreceptor nerve activity remained
      pulse-synchronous after sustained increases in arterial pressure. 2) The
      frequency-domain relationships between the activity in sympathetic nerve pairs
      were altered after sustained elevation in MAP, suggesting a transformation from a
      system of tightly coupled neural circuits to one of multiple generators exerting
      selective control over SND. 3) The most prominent reduction in SND power after
      sustained elevation in MAP occurred in the frequency band containing the cardiac
      cycle, indicating that the prolonged suppression of SND after sustained increases
      in arterial pressure is due primarily to the selective inhibition of cardiac
      related SND bursts. We conclude that sustained elevation in MAP profoundly
      affects the neural circuits responsible for the frequency components of basal SND
      in SH rats.

PMID- 9530236
TI  - Respiratory, metabolic, and acid-base correlates of aerobic metabolic rate
      reduction in overwintering frogs.
AB  - Aerobic metabolic rates (MO2) and respiratory quotients (RQ = CO2 production/MO2)
      were measured contemporaneously in hibernating frogs Rana temporaria (L.),
      submerged for 90 days at 3 degrees C. After 3 mo of submergence in fully aerated
      water, MO2 levels were 61% of those seen at the same temperature before
      hibernation. Over the first 40 days of hibernation, RQ values (< or = 0.82)
      favored a lipid-based metabolism that progressively shifted to an exclusively
      carbohydrate metabolism (RQ = 1.01) by 90 days of hibernation. Liver glycogen
      concentrations fell by 68% during the first 8 wk of submergence, thereafter
      exhibiting a less rapid rate of utilization. Conversely, muscle glycogen
      concentrations remained stable over the first 2 mo of the experiment before
      falling by 33% over the course of the remaining 2 mo, indicating that the frog
      was recruiting muscle glycogen reserves to fuel metabolism. Submerged frogs
      exhibited an extracellular acidosis during the first week of submergence, but
      over the course of the next 15 wk "extracellular pH" values were not
      significantly different from the values obtained from the control air-breathing
      animals. The initial extracellular acidosis was not mirrored in the intracellular
      compartment, and the acid-base state was not significantly different from the
      control values for the first 8 wk. However, over the subsequent 8- to 16-wk
      period, the acid-base status shifted to a lower intracellular pH-HCO3
      concentration set point, indicative of a metabolic acidosis. Even so, there was
      no indication that the acidosis could be attributed to anaerobic metabolism, as
      both plasma and muscle lactate levels remained low and stable. Muscle adenylate
      energy charge and lactate-to-pyruvate and creatine-to-phosphocreatine ratios also
      remained unchanged throughout hibernation. The capacity for profound metabolic
      rate suppression together with the ability to match substrate use to shifts in
      aerobic metabolic demands and the ability to fix new acid-base homeostatic set
      points are highly adaptive, both in terms of survival and reproductive success,
      to an animal that is often forced to overwinter under the cover of ice.

PMID- 9530237
TI  - Atrial natriuretic peptide and mechanisms of cardiovascular control. Role of
      serotonergic receptors.
AB  - Atrial natriuretic peptide (ANP) inhibits renal sympathetic nerve activity
      (RSNA), provided the vagi are intact. Afferents from chemosensitive
      cardiopulmonary receptors are specifically required. Such receptors produce the
      Bezold-Jarisch reflex, are prominent on the ventricular epicardium, and are
      richly supplied with 5-hydroxytryptamine type 3 (5-HT3) receptors. We tested the
      hypothesis that epicardial 5-HT3-sensitive neurons mediate depressor effects of
      ANP. Through a special catheter, anesthetized, sinoaortically denervated rats
      received pericardial test injections of ANP (28-amino acid rat ANP; 100 and 1,000
      ng) in the presence or absence of 5-HT3 antagonist (Ondansetron, 20
      micrograms/kg; n = 9). In other groups we observed the effects of systemic ANP
      while blocking either epicardial or systemic 5-HT3 receptors. Arterial blood
      pressure (ABP), heart rate, and RSNA were recorded continuously. Intravenous ANP
      (100 or 200 ng) decreased ABP and RSNA significantly. In contrast,
      intrapericardial ANP (100 or 1,000 ng) caused no significant fall in ABP or RSNA.
      Both intravenous and pericardial Ondansetron reduced the effects of intravenous
      ANP significantly, but the intravenous antagonism was significantly greater. We
      conclude that epicardial chemosensitive afferents are not sensitive to ANP and
      that sympathoinhibitory effects of ANP arise from a 5-HT3 agonist that cannot be
      produced when ANP is confined to the pericardial space.

PMID- 9530238
TI  - Taste reactivity responses in rats: influence of sex and the estrous cycle.
AB  - Gonadal hormones (e.g., estradiol) may regulate feeding by producing a shift in
      the taste or palatability of food items. This study examined the impact of
      endogenous gonadal hormones on palatability by investigating sex differences in
      taste responsivity, as well as the effect of the estrous cycle on taste
      responsivity, in a rodent model. In the taste reactivity test, male and female
      Long-Evans rats received a brief (1 min) intraoral infusion of one of three
      tastants: sucrose (0.3 M), quinine (0.0003 M), and a sucrose-quinine mixture (0.3
      M sucrose and 0.0003 M quinine). Statistical analyses indicated that female rats
      tested during diestrus or proestrus produced significantly more ingestive
      responses than did male rats and fewer aversive responses than did both male rats
      and female rats tested during estrus or metestrus (P < 0.05). These results
      indicate a sex difference in taste responsivity in the rat that is modulated by
      the reproductive status of female rats. This finding implies a role of gonadal
      hormones in the regulation of taste responsivity in the rat.

PMID- 9530239
TI  - Isolation, visualization, characterization, and osmotic reactivity of crayfish
      BLMV.
AB  - Procedures were developed to isolate basolateral membrane vesicles (BLMV) from
      gill, hepatopancreas, and antennal gland of intermolt freshwater crayfish,
      Procambarus clarkii. Individual procedures involved a discontinuous sucrose
      gradient (gill), a 65% sucrose cushion (hepatopancreas), or differential
      centrifugation (antennal gland). BLMV were visualized, characterized (37 degrees
      C), and tested for osmotic reactivity with a view to using them for Ca2+ uptake
      studies. Mean diameters of BLMV were 159 nm (gill), 363 nm (hepatopancreas), and
      226 nm (antennal gland). Enrichments of basolateral membranes and mitochondria in
      BLMV were, respectively, 18- and 1.7-fold for gill, 9- and 0.4-fold for
      hepatopancreas, and 10- and 1-fold for antennal gland. Apical contamination was
      negligible in BLMV. Percentages of resealing of vesicles as inside out, right
      side out, or leaky/sheets were 17:27:56% (gill), 14:26:60% (hepatopancreas), and
      21:39:40% (antennal gland). Vesicles exhibited osmotic reactivity, as indicated
      by a linear relationship between vesicular 45Ca2+ uptake and osmolality.
      Nonspecific 45Ca2+ binding was 20% in gill, 39% in hepatopancreas, and 31% in
      antennal gland. Data were compared with published values for marine crustaceans.

PMID- 9530240
TI  - Brain type I but not type II IL-1 receptors mediate the effects of IL-1 beta on
      behavior in mice.
AB  - In the immune system, interleukin (IL)-1 beta effects are mediated by the type I
      IL-1 receptors (IL-1RI), whereas the type II IL-1 receptors (IL-1RII) act as
      inhibitory receptors. IL-1RI and IL-1RII are also present in the brain. To study
      their functionality in the brain, mice were centrally treated with neutralizing
      monoclonal antibody (MAb) directed against IL-1RI (35F5, 1 microgram) or against
      IL-1RII (4E2, 2 micrograms) and were centrally injected with recombinant rat IL-1
      beta at a dose (2 ng) that decreased social exploration. Only 35F5 was effective
      in abrogating the behavioral effect of IL-1 beta. Moreover, 4E2 (1 microgram
      i.c.v.) did not potentiate the behavioral response to a subthreshold dose of IL-1
      beta (1 ng i.c.v.). To examine the ability of brain IL-1RI to mediate the effects
      of endogenous IL-1 beta, mice were centrally treated with 35F5 (4 micrograms) and
      peripherally injected with IL-1 beta (1 microgram). Like IL-1 receptor antagonist
      (4 micrograms i.c.v.), 35F5 abrogated the effects of IL-1 beta. These results
      suggest that brain IL-1RI mediates the behavioral effects of IL-1 beta in mice.

PMID- 9530241
TI  - TNF-alpha tolerance blocks LPS-induced hypophagia but LPS tolerance fails to
      prevent TNF-alpha-induced hypophagia.
AB  - To investigate the role of tumor necrosis factor-alpha (TNF-alpha) in bacterial
      lipopolysaccharide (LPS)-induced hypophagia, we tested whether a cross tolerance
      between LPS and TNF-alpha exists with respect to their anorectic effects. Only
      the first of three subsequent intraperitoneal injections of LPS (100
      micrograms/kg body wt) given every second day at dark onset (12:12-h light-dark
      cycle) led to a significant reduction of food intake in male rats. Likewise,
      intraperitoneal injections of human recombinant TNF-alpha (150 micrograms > or =
      3 x 10(6) U/kg body wt) also resulted in tolerance to its hypophagic effect. LPS
      tolerance did not alter the hypophagic response to subsequently injected TNF
      alpha (n = 14). However, TNF-alpha pretreatment completely blocked the hypophagic
      response to LPS (n = 14). The results demonstrate that tolerance to the
      hypophagic effect of exogenous TNF-alpha is sufficient to eliminate LPS-induced
      hypophagia. This is consistent with the hypothesis that endogenous TNF-alpha
      plays a major role in LPS-induced hypophagia. The ineffectiveness of LPS
      tolerance to attenuate TNF-alpha-induced hypophagia is compatible with findings
      demonstrating that reduced TNF-alpha production is an important feature of LPS
      tolerance.

PMID- 9530242
TI  - Behavioral changes in fasting emperor penguins: evidence for a "refeeding signal"
      linked to a metabolic shift.
AB  - This study examines the relationships between metabolic status and behavior in
      spontaneously fasting birds in the context of long-term regulation of body mass
      and feeding. Locomotor activity, escape behavior, display songs, body mass, and
      metabolic and endocrine status of captive male emperor penguins were recorded
      during a breeding fast. We also examined whether body mass at the end of the fast
      affected further survival. The major part of the fast (phase II) was
      characterized by the maintenance of a very low level of locomotor activity, with
      almost no attempt to escape, by an almost constant rate of body mass loss, and by
      steady plasma levels of uric acid, beta-hydroxybutyrate, and corticosterone. This
      indicates behavioral and metabolic adjustments directed toward sparing energy and
      body protein. Below a body mass of approximately 24 kg (phase III), spontaneous
      locomotor activity and attempts to escape increased by up to 8- and 15-fold,
      respectively, and display songs were resumed. This probably reflected an increase
      in the drive to refeed. Simultaneously, daily body mass loss and plasma levels of
      uric acid and corticosterone increased, whereas plasma levels of beta
      hydroxybutyrate decreased. Some experimental birds were seen again in following
      years. These findings suggest that at a threshold of body mass, a metabolic and
      endocrine shift, possibly related to a limited availability of fat stores, acts
      as a "refeeding signal" that improves the survival of penguins to fasting.

PMID- 9530243
TI  - Estradiol phase shifts circannual body mass rhythms of male ground squirrels.
AB  - Gonadectomized male golden-mantled ground squirrels (Spermophilus lateralis) were
      implanted with estradiol benzoate (EB)-filled or empty capsules. Body mass was
      monitored before, during, and for at least 1 yr after hormone treatment. EB
      treatment during the mass-gain phase of the annual cycle significantly
      decelerated increases in body mass; the period of the circannual rhythm (CAR) of
      body mass was 54 days longer in EB- than blank-treated squirrels. Hormone
      treatment during the mass-loss phase accelerated mass loss; although this effect
      only approached statistical significance, some phase markers of the CAR were
      significantly advanced in subsequent cycles. We conclude that, as in females,
      estradiol affects the waveform of the CAR of males differently at different
      phases of the circannual cycle. Sexual differentiation does not eliminate
      responsiveness of CARs of squirrels to estradiol; sex differences, if any, are
      subtle rather than absolute and, in this respect, differ from circadian rhythms.

PMID- 9530244
TI  - Vitamin E ameliorates enhanced renal lipid peroxidation and accumulation of F2
      isoprostanes in aging kidneys.
AB  - Aging results in progressive glomerular sclerosis and reductions in glomerular
      filtration rate (GFR). Oxidative stress may be an important mechanism for the
      aging process, but to date the role of oxidative stress on renal aging has not
      been determined. The present study was performed to determine whether age-related
      alterations in renal hemodynamics and morphology were associated with oxidative
      stress and whether this could be attenuated by chronic administration of vitamin
      E. Rats, aged 13 mo, were given either control diet containing vitamin E 50 IU/kg
      (n = 6) or a high-vitamin E diet (5,000 IU/kg; n = 6) for 9 mo. Another group of
      rats (3-4 mo old; n = 7) served as young controls. Aging was accompanied by a 60%
      reduction in GFR, a threefold increase in renal F2 isoprostanes, newly discovered
      vasoconstrictive F2-like prostaglandins generated by free radical-mediated lipid
      peroxidation. Renal aging was also associated with an increase in oxidant
      sensitive heme oxygenase, advanced glycosylation end products (AGEs), and the AGE
      receptor, RAGE. AGE-RAGE interaction has been shown to induce oxidative stress.
      With high-vitamin E diet, GFR was increased by 50%, F2 isoprostanes were
      suppressed, and expression of heme oxygenase and RAGE was attenuated. There was
      also a tendency for glomerular sclerosis to be attenuated. These data demonstrate
      that age-related decline in renal function is accompanied by oxidative stress and
      that administration of antioxidants, such as vitamin E, could attenuate the
      decline in renal function.

PMID- 9530246
TI  - Microinjection of a cyclooxygenase inhibitor into the anteroventral preoptic
      region attenuates LPS fever.
AB  - Considerable evidence supports the role of prostaglandins in fever production,
      but the neuroanatomic sites of prostaglandin synthesis that produce fever remain
      unknown. With the use of a novel microinjection technique, we injected the
      cyclooxygenase inhibitor ketorolac into the preoptic area (POA) to determine
      which preoptic regions produce the prostaglandins required for fever. Initial
      experiments demonstrated that intravenous ketorolac blocked the fever normally
      produced by lipopolysaccharide (LPS) 5 micrograms/kg i.v. Microinjection of
      ketorolac into the POA had no effect on body temperature, and injection of
      artificial cerebrospinal fluid into the POA did not alter LPS fever. Injection of
      ketorolac into the anteroventral POA markedly decreased the fever produced by
      LPS, compared with injections into more rostral, caudal, or dorsal locations.
      These observations indicate that prostaglandin synthesis in the anteroventral
      preoptic region is necessary for the production of fever.

PMID- 9530245
TI  - Distinct arginase isoforms expressed in primary and transformed macrophages:
      regulation by oxygen tension.
AB  - Experiments were performed to identify arginase isoforms expressed in primary and
      transformed rodent macrophages and to determine the molecular mechanisms for the
      previously observed increase in arginase activity in macrophages cultured in
      hypoxia or anoxia. Results demonstrate the following: 1) mRNA and protein for
      hepatic-type AI arginase are expressed in primary cultures of rat and mouse
      peritoneal macrophages and are enhanced seven- and nine-fold, respectively, by
      lipopolysaccharide (LPS). 2) mRNA for extrahepatic-type AII arginase is
      constitutively expressed in mouse, but not rat, peritoneal macrophages and is
      detected in RAW264.7 cells after LPS treatment; neither J774A.1 nor P388D1 cells
      contain arginase mRNA. 3) AI arginase mRNA, arginase activity in cell lysates,
      and L-arginine flux through arginase in intact cells are all increased in rat
      wound-derived and mouse peritoneal macrophages by hypoxic or anoxic culture; AII
      arginase mRNA is, in contrast, suppressed > 50% by O2 deprivation. 4) Expression
      of the L-arginine transporter mCAT-2 is increased greater than twofold by reduced
      O2 culture. These results demonstrate substantial variability in arginase isoform
      expression among primary and transformed rodent macrophages. They also identify
      AI and AII arginase and the mCAT-2 L-arginine transporter as O2-regulated genes.

PMID- 9530247
TI  - Regulation of the vasomotor activity of lymph microvessels by nitric oxide and
      prostaglandins.
AB  - It was shown previously that the presence of endothelium modulates spontaneous
      vasomotion of small lymphatic vessels. In the present study, we aimed to
      elucidate the nature of endothelium-derived factors, produced in basal conditions
      and in response to agonists, that affect the smooth muscle tone of lymph
      microvessels in vitro. Afferent lymph microvessels were isolated from rat iliac
      lymph nodes, cannulated with glass micropipettes, and pressurized (6 cmH2O), and
      changes in their diameter were investigated with video microscopy. In resting
      conditions, isolated lymph vessels exhibited spontaneous constrictions and
      dilations. The maximum and minimum diameters (Dmax and Dmin) were 149.8 +/- 2.9
      and 85.8 +/- 3.6 microns, respectively. Acetylcholine (ACh, 10(-7) to 10(-5) M)
      and sodium nitroprusside (SNP, 10(-8) to 10(-6) M) temporarily abolished diameter
      oscillations, increasing the diameter of lymphatics dose dependently. For
      example, 10(-5) M ACh and 10(-6) M SNP increased the diameter (Dmax) by 15.2 +/-
      2.2 and 25.0 +/- 2.7 microns, respectively. Treatment of vessels with NG-nitro-L
      arginine (10(-4) M) significantly reduced the amplitude of diameter oscillations
      and nearly completely eliminated ACh-induced dilation of lymph microvessels,
      whereas SNP (10(-6) M) elicited a significantly greater dilation (55.6 +/- 7.5
      microns). Arachidonic acid (AA, 10(-8) to 10(-6) M) constricted (up to 50
      microns), whereas prostaglandin E2 (PGE2, 10(-9) to 10(-7) M) dilated (up to 40
      microns), lymphatic vessels. Indomethacin (10(-5) M) increased both Dmax and Dmin
      and completely inhibited AA-induced constrictions, but did not affect PGE2
      induced dilations of lymph microvessels. AA-induced constrictions of lymphatics
      were converted into dilations after treatment with SQ-29,548, a selective PGH2
      thromboxane A2 (PGH2-TxA2, 10(-6) M) receptor antagonist, whereas PGE2-induced
      dilations were not affected. We conclude that endothelial nitric oxide and
      prostaglandins are important modulators of lymphatic vasomotion, hence pumping
      activity of lymph microvessels in vivo.

PMID- 9530248
TI  - Differential development of umbilical and systemic arteries. I. ANG II receptor
      subtype expression.
AB  - In fetal sheep umbilical responses to angiotensin II (ANG II) exceed those by
      systemic vasculature. Two ANG II receptors (AT) exist, AT1 and AT2, but only AT1
      mediates vasoconstriction in adult tissues. Thus differences in reactivity could
      reflect differences in subtype expression. Using competitive radioligand binding
      assays, we demonstrated AT1 predominance in umbilical arteries and AT2 in femoral
      arteries. Steady-state responses to intravenous ANG II (0.229-1.72
      micrograms/min) were studied in 16 fetuses with umbilical and/or femoral artery
      flow probes without and with local AT1 (L-158,809) or AT2 (PD-123319) blockade.
      ANG II dose dependently (P < 0.001) increased umbilical resistance more than
      arterial pressure (MAP) while decreasing umbilical blood flow. Femoral vascular
      resistance also increased dose dependently (P = 0.02), but responses were less
      than umbilical (P = 0.0001) and paralleled increases in MAP; blood flow was
      unaffected. Cumulative local doses of L-158,809 (125 micrograms) inhibited all
      responses (P < 0.001); however, 1,000 micrograms of the AT2 antagonist had no
      effect. Plasma renin activity (PRA) was unaltered by local AT1 blockade, whereas
      PRA doubled (P = 0.001) after systemic infusion of only 50 micrograms of the AT1
      antagonist and remained elevated. Differences in umbilical and femoral vascular
      responses to ANG II are in large part due to differences in AT subtype
      expression. Furthermore, in fetal sheep the ANG II negative feedback on PRA is
      mediated by AT1 receptors, and it is substantially more sensitive to receptor
      blockade than the vasculature.

PMID- 9530249
TI  - Role of angiotensin in renal sympathetic activation in nephrotic syndrome.
AB  - The effect of type 1 angiotensin II receptor antagonist treatment (losartan) on
      cardiac baroreflex regulation of renal sympathetic nerve activity (RSNA) and
      renal sodium handling in rats with nephrotic syndrome was examined. After
      intravenous losartan administration, with arterial pressure normalized by
      intravenous methoxamine, basal RSNA was decreased 14 +/- 3% in arterial
      baroreceptor-intact rats and by 21 +/- 5% in arterial baroreceptor-denervated
      rats. Intracerebroventricular losartan, which did not affect arterial pressure,
      decreased basal RSNA activity by 15 +/- 1%. Both intravenous and
      intracerebroventricular losartan augmented the renal sympathoinhibitory response
      to acute volume loading, and this was associated with an enhanced natriuretic
      response to the acute volume load. In nephrotic syndrome, acute losartan
      administration improved cardiac baroreflex regulation of RSNA, which was
      associated with improved ability to excrete acute sodium loads.

PMID- 9530250
TI  - Hemodynamic effects of acute stressors in the conscious rabbit.
AB  - Chronically instrumented, conscious rabbits were used to test the hypothesis that
      sensory stimulation with an air jet or oscillation produces differential
      hemodynamic changes that may be appropriate for an active or a passive behavioral
      response, respectively. Both stressors increased arterial pressure, central
      venous pressure, and hindquarters blood flow and produced visceral
      vasoconstriction. Neither stimulus altered hindquarters conductance. Although air
      jet increased heart rate and cardiac output, oscillation did not. The two
      stressors affected arterial baroreflex control of heart rate differently.
      Oscillation reset arterial pressure to a higher level with no change in heart
      rate maximum or minimum, whereas air jet reset both heart rate and arterial
      pressure to higher levels. Neither stressor affected baroreflex sensitivity. We
      conclude that the conscious rabbit shows at least two distinct cardiovascular
      responses when exposed to acute stressors. Air jet produces a cardiovascular
      response including tachycardia, which resembles the defense reaction and appears
      appropriate for active defense or flight. The response to oscillation, on the
      other hand, appears better suited for a passive response such as "freezing"
      behavior. During exposure to either stressor, the baroreflex is altered to allow
      simultaneous increases in heart rate and arterial blood pressure, but the
      sensitivity is maintained, allowing normal moment to moment control of heart
      rate.

PMID- 9530251
TI  - Effects of S-nitroso-N-acetylcysteine on contractile function of reperfused
      skeletal muscle.
AB  - The ultimate goal of replantation and microsurgical reconstructive operations is
      to regain or improve impaired function of the tissue. However, the data related
      to the influence of NO on tissue function are limited. This study evaluated the
      effects of the NO donor S-nitroso-N-acetylcysteine (SNAC) on contractile function
      of skeletal muscle during reperfusion. Forty-nine rats were divided into six
      groups. The extensor digitorum longus (EDL) muscles in groups I and II were not
      subjected to ischemia-reperfusion but were treated with a low (100 nmol/min) or
      high (1 mumol/min) dose of SNAC. In groups III-V, the EDL underwent 3 h of
      ischemia and 3 h of reperfusion and was also treated with low (100 nmol/min) or
      high doses (1 or 5 mumol/min) of SNAC. Group VI was a phosphate-buffered saline
      (PBS)-treated control group. Twenty additional animals were used to document
      systemic effects of SNAC and PBS only. SNAC or PBS was infused for 6.5 h,
      beginning 30 min before ischemia and continuing throughout the duration of
      reperfusion. Contractile testing compared the maximal twitch force, isometric
      tetanic contractile forces, fatigue, and fatigue half time of the experimental
      EDL and the contralateral nontreated EDL. The findings indicate that 1) SNAC does
      not influence contractile function of EDL muscle not subjected to ischemia
      reperfusion, 2) SNAC significantly protects the contractile function of ischemic
      skeletal muscle against reperfusion injury in the early reperfusion period, and
      3) the protective role of SNAC is critically dosage dependent; protection is lost
      at higher doses. The conclusion from this study is that supplementation with
      exogenous NO exerts a protective effect on the tissue against reperfusion injury.

PMID- 9530252
TI  - Effects of bright light on age-related changes in the locomotor activity of
      Syrian hamsters.
AB  - Syrian hamsters display age-related changes in the expression of circadian
      rhythms and in responsiveness of the circadian system to photic and non-photic
      stimuli. This study characterized the effects of age on the locomotor activity
      rhythm of middle-aged and old hamsters and evaluated the effects of strengthening
      the entraining light signal. Compared with young (4.5 mo) animals, middle-aged
      (11.25 mo) and old (16 mo) animals displayed increased daily bouts of activity (P
      < 0.001) and reduced total daily activity and activity rhythm amplitude (P <
      0.05) in 14:10-h light-dark cycles. After the light intensity was increased from
      300 to 1,500 lx during the light cycle, middle-aged hamsters demonstrated
      decreased daily activity bouts (P < 0.05) and increased total daily activity (P <
      or = 0.01) and activity rhythm amplitude (P < or = 0.001) compared with controls
      maintained in 300 lx. The pattern of changes in the activity rhythm of old
      experimental animals was similar to trends observed in middle-aged experimental
      hamsters, although not as robust. Thus age-related changes in the activity rhythm
      are occurring by middle age in hamsters, and the provision of stronger entraining
      signals may lead to more stable circadian organization.

PMID- 9530253
TI  - Menhaden oil prevents but does not reverse sucrose-induced insulin resistance in
      rats.
AB  - Although fish oil supplementation may prevent the onset of diet-induced insulin
      resistance in rats, it appears to worsen glycemic control in humans with existing
      insulin resistance. In the present study, the euglycemic, hyperinsulinemic (4x
      basal) clamp technique with [3-3H]glucose and 2-deoxy-[1-14C]glucose was used to
      directly compare the ability of fish oil to prevent and reverse sucrose-induced
      insulin resistance. In study 1 (prevention study), male Wistar rats were fed a
      purified high-starch diet (68% of total energy), high-sucrose diet (68% of total
      energy), or high-sucrose diet in which 6% of the fat content was replaced by
      menhaden oil for 5 wk. In study 2 (reversal study), animals were fed the high
      starch or high-sucrose diets for 5 wk and then the sucrose animals were assigned
      to one of the following groups for an additional 5 wk: high starch, high sucrose,
      or high sucrose with 6% menhaden oil. Rats fed the high-starch diet for 10 wk
      served as controls. In study 3 (2nd reversal study), animals followed a similar
      diet protocol as in study 2; however, the reversal period was extended to 15 wk.
      In study 1, the presence of the fish oil in the high-sucrose diet prevented the
      development of insulin resistance. Glucose infusion rates (GIR, mg.kg-1.min-1)
      were 17.0 +/- 0.9 in starch, 10.6 +/- 1.7 in sucrose, and 15.1 +/- 1.5 in sucrose
      with fish oil animals. However, in study 2, this same diet was unable to reverse
      sucrose-induced insulin resistance (GIR, 16.7 +/- 1.4 in starch, 7.1 +/- 1.5 in
      sucrose, and 4.8 +/- 0.9 in sucrose with fish oil animals). Sucrose-induced
      insulin resistance was reversed in rats that were switched back to the starch
      diet (GIR, 18.6 +/- 3.0). Results from study 3 were similar to those observed in
      study 2. In summary, fish oil was effective in preventing diet-induced insulin
      resistance but not able to reverse it. A preexisting insulin-resistant
      environment interferes with the positive effects of menhaden oil on insulin
      action.

PMID- 9530254
TI  - Myocardial and plasma renin-angiotensinogen dynamics during pressure-induced
      cardiac hypertrophy.
AB  - Plasma and left ventricular (LV) renin and angiotensinogen concentrations were
      assessed in a rat model of pressure-overload cardiac hypertrophy to determine if
      myocardial levels remained proportional to plasma levels over time. Three days
      after subdiaphragmatic aortic constriction (AC), LV hypertrophy was evident and
      renin concentrations in both plasma and LV, although not significantly elevated,
      were positively correlated with relative cardiac mass. After 42 days AC, LV
      hypertrophy remained, plasma and LV renin and angiotensinogen levels were not
      different from shams, and there was no correlation between renin and relative
      cardiac mass. Furthermore, LV renin and angiotensinogen concentrations remained
      at approximately 25 and 4%, respectively, of those in plasma throughout the
      experiment. Myocytes from 3-day AC and sham-treated rats contained little renin
      as did LV from 48-h anephric rats. Incubations using calculated concentrations of
      myocardial interstitial renin and angiotensinogen revealed significant
      angiotensin I generation. These data suggest that LV renin in this model varies
      directly with plasma renin, is confined to the interstitial space, and can
      generate significant intramyocardial angiotensin I.

PMID- 9530255
TI  - Photic resetting of intrinsic rhythmicity of the rat suprachiasmatic nucleus
      under various photoperiods.
AB  - To date, photic entrainment of the mammalian circadian system has been studied by
      following phase shifts of overt rhythms in the periphery governed by a circadian
      pacemaker located in the suprachiasmatic nucleus (SCN). The present study follows
      for the first time photic resetting of intrinsic rhythmicity of the SCN itself.
      Rats maintained under either a shorter photoperiod, with 12 h of light and 12 h
      of darkness per day, or under a long, 18:6-h light-dark photoperiod were exposed
      to a light stimulus during the dark period and then released into darkness, and
      the next day the SCN rhythm in the light-stimulated c-Fos protein
      immunoreactivity was followed as a marker of the SCN endogenous rhythmicity.
      After a light stimulus in the early night, the evening rise in the photic
      elevation of Fos protein photoinduction as well as the morning decline were phase
      delayed within one cycle. After a light stimulus in the late night, only the
      morning decline in the photic elevation of Fos was phase advanced the next night,
      not the evening rise; consequently, the interval enabling high photic elevation
      of Fos was reduced. After a light stimulus was administered around the middle of
      the night, the next night the evening rise in the light-stimulated Fos was
      eventually phase delayed, the morning decline was phase advanced, and the rhythm
      amplitude was reduced significantly; under 18:6-h light-dark, a mere 5-min light
      exposure exhibited such effects. The data indicate that resetting of the SCN
      rhythmicity in the light-elevated c-Fos 1 day after a resetting stimulus
      administration, i.e., during transient cycles, may proceed via nonparallel phase
      shifts of the evening rise and of the morning decline of the light-stimulated
      Fos, and via amplitude lowering and suggest a complex circadian pacemaking system
      in the rat SCN.

PMID- 9530256
TI  - Thyroid hormone-induced upregulation of Na+ channels and Na(+)-K+ pumps:
      implications for contractility.
AB  - We have previously observed in rat soleus muscle that endurance is a function of
      the ratio between the concentration of Na+ channels and Na(+)-K+ pumps [Harrison,
      A. P., O. B. Nielsen, and T. Clausen. Am. J. Physiol. 272 (Regulatory Integrative
      Comp. Physiol. 41): R1402-R1408, 1997]. In this study we explore this
      relationship further by comparing the changes in Na+ channel and Na(+)-K+ pump
      concentrations induced by injections of 3,5,3'-triiodothyronine (T3) with
      endurance. T3 induced upregulation of the concentration of Na+ channels and Na(+)
      K+ pumps, which was associated with a progressive loss of contractile endurance.
      The increase in Na+ channels preceded that of the Na(+)-K+ pumps and amounted to
      49 and 52% (both P < 0.01) after 48 and 72 h of T3 treatment, respectively.
      Concomitantly, during 90-Hz stimulation, the initial rate of force decline
      increased by 42 and 45% after 48 and 72 h of T3 treatment, respectively (both P <
      0.001). These observations are important for an understanding of the fatigue
      associated with hyperthyroidism and add further support to the hypothesis that
      muscle endurance depends on the leak-to-pump ratio for Na+.

PMID- 9530257
TI  - Does muscle creatine phosphokinase have access to the total pool of
      phosphocreatine plus creatine?
AB  - Two fundamental assumptions underlie currently accepted dogma on creatine
      phosphokinase (CPK) function in phosphagen-containing cells: 1) CPK always
      operates near equilibrium and 2) CPK has access to, and reacts with, the entire
      pool of phosphocreatine (PCr) and creatine (Cr). We tested the latter assumption
      in fish fast-twitch or white muscle (WM) by introducing [14C]Cr into the WM pool
      in vivo. To avoid complications arising from working with muscles formed from a
      mixture of fast and slow fibers, it was advantageous to work with fish WM because
      it is uniformly fast twitch and is anatomically separated from other fiber types.
      According to current theory, at steady state after [14C]Cr administration, the
      specific activities of PCr and Cr should be the same under essentially all
      conditions. In contrast, we found that, in various metabolic states between rest
      and recovery from exercise, the specific activity of PCr greatly exceeds that of
      Cr. The data imply that a significant fraction of Cr is not free to rapidly
      exchange with exogenously added [14C]Cr. Releasing of this unlabeled or "cold" Cr
      on acid extraction accounts for lowered specific activities. This unexpected and
      provocative result is not consistent with traditional models of phosphagen
      function.

PMID- 9530258
TI  - Postganglionic sympathetic neurons express endothelin.
AB  - Endothelin (ET) is a peptide originally identified as an endothelial-derived
      vasoconstrictor. It is now recognized that ET is produced by and acts on many
      other tissues including the brain and spinal cord, where it is believed to
      modulate neurotransmission. The present studies demonstrate that ET is
      synthesized by and secreted from postganglionic sympathetic neurons. With the use
      of Northern analysis, ET-1 mRNA was detected in cultures of sympathetic superior
      cervical ganglion (SCG) neurons isolated from 3- to 5-day old rat pups. ET-1 and
      ET-3 peptides were also detected in cultured SCG neurons using
      immunohistochemistry. ET-1 (50 pg/106 cells) and ET-3 (173 pg/106 cells) were
      detected by radioimmunoassay of media conditioned by cultured SCG. ET-1 (77 pg/mg
      protein) and ET-3 (30 pg/mg protein) were also detected by radioimmunoassay of
      extracts of adult SCG.

PMID- 9530259
TI  - Integrating multiple paracrine regulators of renal microvascular dynamics.
AB  - There has been tremendous growth in our knowledge about the multiple interacting
      mechanisms that regulate renal microvascular function. Paracrine signals
      originating from endothelial and epithelial cells exert profound influences on
      the basal tone and reactivity of the pre- and postglomerular arterioles.
      Selective responsiveness of these arterioles to various stimuli is possible
      because of differential activating mechanisms in vascular smooth muscle cells of
      afferent and efferent arterioles. Afferent arterioles rely predominantly on
      voltage-dependent calcium channels, while efferent arterioles utilize other
      mechanisms for calcium entry as well as intracellular calcium mobilization. The
      autoregulatory responses of preglomerular arterioles exemplify the selectivity of
      these complex control mechanisms. The myogenic mechanism responds to increases in
      renal perfusion pressure through "stretch-activated" cation channels that lead to
      depolarization, calcium entry, and vascular contraction. Autoregulatory
      efficiency is enhanced by the tubuloglomerular feedback (TGF) mechanism which
      responds to flow-dependent changes in tubular fluid composition at the level of
      the macula densa and transmits signals to the afferent arterioles to alter the
      activation state of voltage-dependent calcium channels. Recent studies have
      implicated extracellular ATP as one paracrine factor mediating TGF and
      autoregulatory related signals to the afferent arterioles. Other paracrine agents
      including nitric oxide, angiotensin II, adenosine, and arachidonic acid
      metabolites modulate vascular responsiveness in order to maintain an optimal
      balance between the metabolically determined reabsorptive capabilities of the
      tubules and the hemodynamically dependent filtered load.

PMID- 9530260
TI  - Model explaining the relation between distal nephron Li+ reabsorption and urinary
      Na+ excretion in rats.
AB  - Li+ may be reabsorbed via an amiloride-sensitive mechanism in the collecting
      ducts of rats administered a low-Na+ diet. This was investigated by measuring the
      increase in fractional urinary excretion of Li+ (FELi) in response to amiloride
      in conscious rats at two different levels of plasma Li+ concentration and after
      administration of bendroflumethiazide (BFTZ), angiotensin III (ANG III), and
      aldosterone (Aldo). The results confirmed that amiloride increased (FELi) in rats
      on a low-Na+ diet (20 +/- 1 to 35 +/- 1%, means +/- SE), whereas no increase was
      observed in rats on a normal Na+ diet (37 +/- 1 to 38 +/- 1%). The lithiuretic
      effect of amiloride was 1) abolished by preadministration of BFTZ (32 +/- 1 to 33
      +/- 2%) to Na(+)-deprived rats and 2) increased by ANG III (27 +/- 3 to 33 +/-
      2%) and Aldo (25 +/- 2 to 37 +/- 2%) in Na(+)-replete rats. Amiloride-induced
      changes in FELi were independent of plasma Li+ concentration but inversely
      related to the fractional excretion of Na+ and the amiloride-sensitive excretion
      of K+. These results are compatible with the hypothesis that a low tubular Na+
      concentration reduces end-tubular Na+ reabsorption and results in
      hyperpolarization of the apical membrane, thus favoring Li+ uptake into the
      cells.

PMID- 9530261
TI  - Water and solute permeabilities of medullary thick ascending limb apical and
      basolateral membranes.
AB  - The medullary thick ascending limb (MTAL) reabsorbs solute without water and
      concentrates NH4+ in the interstitium without a favorable pH gradient, activities
      which require low water and NH3 permeabilities. The contributions of different
      apical and basolateral membrane structures to these low permeabilities are
      unclear. We isolated highly purified apical and basolateral MTAL plasma membranes
      and measured, by stopped-flow fluorometry, their permeabilities to water, urea,
      glycerol, protons, and NH3. Osmotic water permeability at 20 degrees C averaged
      9.4 +/- 0.8 x 10(-4) cm/s for apical and 11.9 +/- 0.5 x 10(-4) cm/s for
      basolateral membranes. NH3 permeabilities at 20 degrees C averaged 0.0023 +/-
      0.00035 and 0.0035 +/- 0.00080 cm/s for apical and basolateral membranes,
      respectively. These values are consistent with those obtained in isolated
      perfused tubules and can account for known aspects of MTAL function in vivo.
      Because the apical and basolateral membrane unit permeabilities are similar, the
      ability of the apical membrane to function as the site of barrier function arises
      from its very small surface area when compared with the highly redundant
      basolateral membrane.

PMID- 9530262
TI  - Potential autocrine and paracrine mechanisms of recovery from mechanical injury
      of renal tubular epithelial cells.
AB  - The present studies were done to clarify potential pathways of the nephrogenic
      repair process. Media removed from mechanically injured vascular smooth muscle
      cells and LLC-PK1 renal tubular epithelial cells significantly stimulated
      [3H]thymidine uptake and cell number in quiescent LLC-PK1 cells, demonstrating
      the existence of potential autocrine and paracrine pathways of nephrogenic
      repair. The effect of mechanical injury resulting in release of one or more
      growth factors into culture media was also found in the opossum kidney OK renal
      tubular cell line. The nonspecific peptide growth factor antagonist suramin
      inhibited the effect of media from injured LLC-PK1 cells to stimulate
      [3H]thymidine uptake in quiescent LLC-PK1 cells. Exposure of quiescent LLC-PK1
      cells to six growth factors, including acidic and basic fibroblastic growth
      factors (aFGF and bFGF), platelet-derived growth factors AA and BB (PDGF-AA and
      PDGF-BB), endothelin-2, and hepatocyte growth factor, reproduced the biological
      responses seen when quiescent LLC-PK1 cells were exposed to media from injured
      cells. Immunoblotting and enzyme-linked immunosorbent assay experiments
      demonstrated the presence of aFGF, bFGF, and PDGF-BB but not other candidate
      growth factors in the media from injured LLC-PK1 cells. A neutralizing antibody
      directed against bFGF attenuated the effect of media from injured cells to
      stimulate [3H]thymidine uptake in serum-starved LLC-PK1 cells. These results
      demonstrate that mechanical injury to renal tubular epithelial cells results in
      release of aFGF, bFGF, and PDGF-BB into the media and suggests that bFGF may be
      involved in an autocrine fashion to promote recovery from injury.

PMID- 9530263
TI  - Arginase activity is modulated by IL-4 and HOArg in nephritic glomeruli and
      mesangial cells.
AB  - Arginase shares a common substrate, L-arginine, with nitric oxide synthase (NOS).
      Both enzymes are active at inflammatory sites. To understand regulation of
      arginase and its relationship to nitric oxide (NO) production, we studied effects
      of NG-hydroxy-L-arginine (HOArg) and interleukin-4 (IL-4) on urea and NO2-
      synthesis by glomeruli during rat immune glomerulonephritis and compared these
      with macrophages and glomerular mesangial cells (MC). In nephritic glomeruli,
      elicited macrophages, and MC stimulated with IL-1 and adenosine 3',5'-cyclic
      monophosphate agonists, increased arginase and induced NOS activity was found.
      Urea production was inhibited by HOArg and increased by IL-4. NO inhibition [NG
      monomethyl-L-arginine (L-NMMA)] increased arginase activity in nephritic
      glomeruli and macrophages but not MC. NO2- synthesis was inhibited by L-NMMA and
      IL-4. It was increased with HOArg under conditions of NO inhibition. In contrast,
      in normal glomeruli and basal MC, where there was no induced NO synthesis, IL-4
      had no effect on arginase activity, whereas HOArg consistently reduced it in
      glomeruli only. Type II arginase (Arg II) mRNA was detected in normal glomeruli;
      nephritic glomeruli expressed both Arg I and Arg II mRNAs. This is the first
      demonstration of arginase modulation in glomeruli and MC and of the expression of
      arginase isoforms in glomeruli. The differential responses to two endogenous
      compounds generated by inflammation suggest this may be part of coordinated
      regulation of arginase and inducible NOS in immune injury, whereby arginase is
      inhibited during high-output NO production and stimulated with NO suppression.
      This, together with control of arginase and NOS isoforms, may be important in
      controlling the balance of inflammatory and repair mechanisms.

PMID- 9530264
TI  - Regulation of cyclooxygenase expression in the kidney by dietary salt intake.
AB  - The present studies were undertaken to determine the effect of dietary salt
      intake on the renal expression of cyclooxygenase-1 (COX-1) and -2 COX-2). Protein
      levels were assessed by Western blotting, and mRNA expression was assessed by
      reverse transcription-polymerase chain reaction (RT-PCR) on cDNA prepared from
      kidney regions, dissected nephron segments, and cultured renal cells. Both
      isoforms were expressed at high levels in inner medulla (IM), with low levels
      detected in outer medulla and cortex. COX-1 mRNA was present in the glomerulus
      and all along the collecting duct, whereas COX-2 mRNA was restricted to the
      macula densa-containing segment (MD), cortical thick ascending limb (CTAL), and,
      at significantly lower levels, in the inner medullary collecting duct. Both
      isoforms were highly expressed at high levels in cultured medullary interstitial
      cells and at lower levels in primary mesangial cells and collecting duct cell
      lines. Maintaining rats on a low- or high-NaCl diet for 1 wk did not affect
      expression of COX-1. In IM of rats treated with a high-salt diet, COX-2 mRNA
      increased 4.5-fold, and protein levels increased 9.5-fold. In contrast, cortical
      COX-2 mRNA levels decreased 2.9-fold in rats on a high-salt diet and increased
      3.3-fold in rats on a low-salt diet. A low-salt diet increased COX-2 mRNA 7.7
      fold in MD and 3.3-fold in CTAL. Divergent regulation of COX-2 in cortex and
      medulla by dietary salt suggests that prostaglandins in different kidney regions
      serve different functions, with medullary production playing a role in promoting
      the excretion of salt and water in volume overload, whereas cortical
      prostaglandins may protect glomerular circulation in volume depletion.

PMID- 9530266
TI  - ANG II and vasopressin stimulate calcium entry in dispersed smooth muscle cells
      of preglomerular arterioles.
AB  - Calcium signaling mechanisms were examined in vessel segments and dispersed
      single smooth muscle cells (SMC) of interlobular arteries and afferent arterioles
      (< 50 microns diameter) from the rat kidney. These resistance vessels were
      isolated from rat kidneys, using an iron oxide-sieving technique with subsequent
      collagenase digestion. Individual cells were identified by their characteristic
      oval appearance and positive staining for smooth muscle-specific alpha-actin and
      heavy chain myosin SM-1 and SM-2. Cytosolic calcium concentration ([Ca2+]i) was
      measured using fura 2 ratiometric fluorescence at 340 and 380 nm wavelength with
      a microscope-based photometer. Angiotensin II (ANG II) and arginine vasopressin
      (AVP), at concentrations of 10(-10)-10(-6) M, produced dose-dependent increases
      in [Ca2+]i; maximum increases were 221 +/- 49 nM for ANG II and 237 +/- 49 nM for
      AVP. The temporal response patterns for both agonists were characterized by a
      square-shaped, immediate step increase in [Ca2+]i to a near maximum level that
      was maintained through the recording period of 150-200 s. Responses of individual
      dispersed SMC and short vessel segments were similar. Losartan antagonized the
      action of ANG II, indicating mediation by AT1 receptors on preglomerular
      arteriolar SMC. The V1-selective antagonist [d(CH2)5Tyr(Me)2Tyr(NH2)9]AVP
      completely inhibited AVP-induced [Ca2+]i changes. The importance of calcium entry
      in hormone-induced changes in [Ca2+]i was demonstrated by the finding that
      neither ANG II nor AVP elicited a [Ca2+]i response in media rendered nominally
      calcium free by addition of ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'
      tetraacetic acid. Calcium entry occurred primarily through L-type, voltage-gated
      calcium channels as the dihydropyridine, nifedipine, completely prevented or
      reversed [Ca2+]i changes normally elicited by either hormone. Our results provide
      new information about the similarity of calcium signaling in single SMC and short
      segments freshly isolated from renal interlobular arteries and afferent
      arterioles. The observations indicate that AT1 and V1 receptors are coupled to
      signal transduction pathways leading to rapid changes in [Ca2+]i. Calcium
      mobilization appears to play a minor to nonexistent role under the experimental
      conditions. The predominant mechanism involves calcium entry through
      dihydropyridine-sensitive, voltage-gated calcium channels in single SMC from
      these resistance vessels.

PMID- 9530265
TI  - The endogenous insulin-like growth factor system in radiocontrast nephropathy.
AB  - The response of insulin-like growth factor (IGF) I in acute renal failure was
      evaluated in a model of radiocontrast nephropathy associated with selective
      necrosis of medullary thick ascending limbs. In brief, rats were administered
      radiocontrast medium or vehicle injections for controls after combined inhibition
      of prostanoids and nitric oxide. Twenty-four hours after the insult, tissue mRNAs
      for IGF-I, the IGF-I receptor, and IGF-binding proteins (IGFBP) 1 and 3 were
      assayed in cortex, medulla, and liver by solution hybridization-RNase protection
      assay, and IGFBPs were measured in serum and tissue by Western ligand blotting.
      Cortical IGF-1 increased, whereas medullary IGF-I mRNA decreased. Renal IGFBPs
      decreased, whereas IGFBP-1 mRNA increased. The IGF system in the liver was
      unchanged. We conclude that general changes in renal IGFBPs in this experimental
      model of acute renal failure might increase the level of cortical IGF-I in a way
      that could modulate medullary recovery.

PMID- 9530267
TI  - Recovery of cellular functions following oxidant injury.
AB  - This study investigated the recovery of renal proximal tubule cellular (RPTC)
      functions following oxidant-induced sublethal injury. tert-Butylhydroperoxide
      (TBHP) treatment resulted in 24% cell death and loss 4 h following the exposure.
      The remaining sublethally injured RPTC proliferated, and monolayer DNA content
      returned to control values on day 4 following TBHP exposure. Basal oxygen
      consumption (Qo2) and ATP content in sublethally injured RPTC were decreased 64
      and 63%, respectively, at 4 h and returned to control values on day 6. Net
      lactate consumption decreased 71% at 4 h and returned to control values on day 4.
      In contrast, net glutamine consumption increased 2.7-fold at 4 h and returned to
      control values on day 6. Ouabain-sensitive Qo2, Na(+)-K(+)
      adenosinetriphosphatase (Na(+)-K(+)-ATPase) activity, and Na(+)-coupled glucose
      transport were inhibited 77, 88, and 83%, respectively, at 4 h and recovered to
      control values on day 6. These data show that 1) mitochondrial function, Na(+)
      K(+)-ATPase activity, active Na+ transport, and Na(+)-coupled glucose transport
      are decreased in sublethally injured RPTC following oxidant exposure and are
      repaired over time; 2) monolayer regeneration precedes the recovery of
      mitochondrial and transport functions, and 3) sublethal injury and subsequent
      regeneration are associated with alterations in metabolic substrate utilization.
      These results suggest that oxidant-induced sublethal injury to RPTC may
      contribute to renal dysfunction and that RPTC can repair and regain cellular
      functions following oxidant injury.

PMID- 9530268
TI  - Neuronal nitric oxide synthase modulates rat renal microvascular function.
AB  - This study was performed to determine the influence of neuronal nitric oxide
      synthase (nNOS) on renal arteriolar tone under conditions of normal, interrupted,
      and increased volume delivery to the macula densa segment and on the
      microvascular responses to angiotensin II (ANG II). Experiments were performed in
      vitro on afferent (21.2 +/- 0.2 microns) and efferent (18.5 +/- 0.2 microns)
      arterioles of kidneys harvested from male Sprague-Dawley rats, using the blood
      perfused juxtamedullary nephron technique. Superfusion with the specific nNOS
      inhibitor, S-methyl-L-thiocitrulline (L-SMTC), decreased afferent and efferent
      arteriolar diameters, and these decreases in arteriolar diameters were prevented
      by interruption of distal volume delivery by papillectomy. When 10 mM
      acetazolamide was added to the blood perfusate to increase volume delivery to the
      macula densa segment, afferent arteriolar vasoconstrictor responses to L-SMTC
      were enhanced, but this effect was again completely prevented after papillectomy.
      In contrast, the arteriolar diameter responses to the nonselective NOS inhibitor,
      N omega-nitro-L-arginine (L-NNA) were only attenuated by papillectomy. L-SMTC (10
      microM) enhanced the efferent arteriolar vasoconstrictor response to ANG II but
      did not alter the afferent arteriolar vasoconstrictor responsiveness to ANG II.
      In contrast, L-NNA (100 microM) enhanced both afferent and efferent arteriolar
      vasoconstrictor responses to ANG II. These results indicate that the modulating
      influence of nNOS on afferent arteriolar tone of juxtamedullary nephrons is
      dependent on distal tubular fluid flow. Furthermore, nNOS exerts a differential
      modulatory action on the juxtamedullary micro-vasculature by enhancing efferent,
      but not afferent, arteriolar responsiveness to ANG II.

PMID- 9530269
TI  - Dissociation of K channel density and ROMK mRNA in rat cortical collecting tubule
      during K adaptation.
AB  - The density of conducting K channels in the apical membrane of the rat cortical
      collecting tubule (CCT) is increased by a high-K diet. To see whether this
      involved increased abundance of mRNA coding for K channel protein, we measured
      the relative amounts of mRNA for ROMK, the clone of the gene thought to encode
      the secretory K channel in the CCT. Tubules were isolated and fixed for in situ
      hybridization with a probe based on the ROMK sequence. Radiolabeled probe
      associated with the tubule was quantified using densitometric analysis of the
      autoradiographic images of the tubules. The densitometry signal was shown to be
      proportional to the amount of radioactive probe in the sample and to the time of
      exposure of the film. The technique was able to detect an approximately twofold
      increase in the abundance of mRNA coding for the water channel aquaporin 3
      (AQP3), in response to a 30-h dehydration period. Tubules from rats fed a normal
      diet or a high-K (10% KCl) diet had equal amounts of ROMK mRNA. This suggests
      that an increase in the abundance of mRNA does not underlie the increase in
      channel density observed under these conditions.

PMID- 9530270
TI  - Soy protein modification of rat polycystic kidney disease.
AB  - We undertook a study to determine whether soy protein feeding would ameliorate
      renal injury in the Han:SPRD-cy rat model of polycystic kidney disease (PKD).
      Male offspring of Han:SPRD-cy heterozygotes received isocaloric diets based on
      20% casein or 20% heat-treated soy protein at weaning ad libitum for 8 wk. Soy
      fed animals demonstrated lower serum creatinine (66 vs. 125 mumol/l; P = 0.002),
      lower urinary ammonium excretion (0.080 vs. 0.173 mmol/kg; P = 0.01), reduced
      renal cysts (0.98 vs. 4.92 ml/kg body wt, P < 0.0001), renal fibrosis (0.79 vs.
      1.4 ml/kg; P = 0.016), macrophage infiltration, renal tubular cell proliferation,
      and apoptosis. Proton nuclear magnetic resonance (1H-NMR) studies of urine
      demonstrated that soy diet was associated with increased losses of citric acid
      cycle organic anions. 1H-NMR of perchloric acid-extracted tissue found that
      levels of succinate were not depleted in soy-fed animals, despite increased
      urinary losses. Soy-fed animals had marked elevation of tissue betaine (P <
      0.001), with reduced taurine and cholines, compared with casein-fed animals (P <
      0.001). Soy feeding dramatically reduces both tubular and interstitial pathology
      in the Han:SPRD-cy rat model of PKD, through mechanisms that remain to be
      determined.

PMID- 9530271
TI  - Development of pH regulatory transport in glomerular mesangial cells.
AB  - Developmental changes in activity or expression of transporters may account for
      alterations in cell behavior as the nonpolarized cell matures. We sought to
      ascertain whether there is a maturational change in each of the major acid-base
      transporters in the developing mesangial cell (MC), the Na/H exchanger, Na
      dependent Cl/HCO3 exchanger, and the Cl/HCO3 exchanger. Intracellular pH (pHi)
      was determined by the use of the fluorescent pH-sensitive dye, 2',7'-bis(2-
      carboxyethyl)-5(6)-carboxyfluorescein (BCECF). We assessed transporter activity
      by studying recovery from an acid load (NH4/NH3) in CO2/HCO3. In adult MCs, Na/H
      exchanger was responsible for 35.2 +/- 4.3% of steady-state pHi, whereas the Na
      dependent Cl/HCO3 exchanger contributed 58.7 +/- 6.1 (n = 14). In term MCs
      (tMCs), from days 1-3 after birth, the Na/H exchanger contributes 62.9 +/- 7.8%
      (n = 11, P < 0.001 vs. adult), whereas the Na-dependent Cl/HCO3 exchanger
      contributes 34.0 +/- 5.7% (n = 12, P < 0.001 vs. adult), to the rate of recovery
      from an acid load in these cells. However, in tMCs (days 4-6), the Na/H
      contributes 47.2 +/- 5.9% (n = 8, P < 0.05 vs. adult), whereas the Na-dependent
      Cl/HCO3 exchanger contributes 48.7 +/- 7.3% (n = 13, P < 0.05 vs. adult), to the
      rate of recovery. tMCs (days 6-12) yielded transporter activity that was not
      statistically different than adult MCs (37.8 +/- 4.9 and 54.3 +/- 10.2% for Na/H
      and Na-dependent Cl/HCO3, respectively). The magnitude of the stimulated response
      to angiotensin II by Na/H and Na-dependent Cl/HCO3 exchanger in adult and tMCs is
      unchanged throughout development. The Na/H exchanger appears to play a greater
      role in pHi homeostasis earlier on in development, and this may reflect
      developmental needs of the maturing cell.

PMID- 9530272
TI  - Extrarenal resistance to atrial natriuretic peptide in rats with experimental
      nephrotic syndrome.
AB  - Nephrotic syndrome is associated with resistance to the renal actions of atrial
      natriuretic peptide (ANP). We performed experiments in anesthetized, acutely
      nephrectomized rats 21-28 days after injection of adriamycin (7-8 mg/kg i.v.) or
      9-14 days after injection of anti-Fx1A antiserum (5 ml/kg i.p.) (passive Heymann
      nephritis; PHN) to test whether extrarenal resistance also occurred. Proteinuria
      was significantly elevated in both models compared with controls before study.
      ANP infusion (1 microgram.kg-1.min-1) caused arterial pressure to decrease
      similarly in control rats, adriamycin-treated rats, and rats with PHN (by 8.2 +/-
      1.0, 9.4 +/- 2.3, and 9.0 +/- 2.0%, respectively; all P < 0.05 vs. both baseline
      and vehicle-infused control rats). In control rats, hematocrit increased
      progressively to a maximal value 9.5 +/- 0.9% over baseline as a result of the
      infusion, an increase corresponding to a reduction in plasma volume of 16.1 +/-
      0.9%. The ANP-induced increase in hematocrit was preserved in adriamycin-treated
      rats (9.2 +/- 1.3%) but was markedly blunted in rats with PHN (2.4 +/- 1.3%; P <
      0.0001 vs. ANP infusion in control rats). ANP infusion increased plasma ANP
      levels to the same extent in the three groups, whereas plasma guanosine 3',5'
      cyclic monophosphate was significantly lower in rats with PHN compared with both
      control and adriamycin-treated rats. Infusion of a subpressor dose of angiotensin
      II (ANG II, 2.5 ng.kg-1.min-1) fully restored the ANP-induced increase in
      hematocrit in rats with PHN. This study demonstrates that 1) the
      hemoconcentrating and hypotensive actions of ANP are preserved in adriamycin
      treated rats, 2) the effect of ANP on hematocrit and fluid distribution is
      blunted in rats with PHN while its hypotensive action is preserved, and 3) low
      level ANG II infusion normalizes the hemoconcentrating effect of exogenously
      infused ANP in rats with PHN. Thus deficient ANG II generation in rats with PHN,
      but not adriamycin nephrosis, may contribute to extrarenal ANP resistance.

PMID- 9530273
TI  - Phosphoinositide signaling in rat inner medullary collecting duct.
AB  - Previous studies in microdissected rat inner medullary collecting duct (IMCD)
      segments have demonstrated that carbachol, arginine vasopressin (AVP), and the V2
      vasopressin receptor agonist 1-desamino-8-D-arginine vasopressin (DDAVP) induce a
      similar increase in intracellular Ca2+. The present study tested whether these
      agents activate the phosphoinositide hydrolysis pathway. In intracellular
      inositol 1,4,5-trisphosphate (IP3) measurements, we found that IMCD suspensions
      incubated with AVP or DDAVP (10(-8) M) displayed no measurable increase in IP3,
      whereas IMCD suspensions incubated with the muscarinic cholinergic agent
      carbachol (100 microM) induced a significant increase in IP3 production.
      Similarly, carbachol, but not AVP or DDAVP, induced a significant increase in
      membrane-associated protein kinase C (PKC) enzyme activity. To test what specific
      PKC isoforms are activated by carbachol in IMCD, we first characterized the PKC
      isoforms in IMCD suspensions by immunoblotting using affinity-purified antibodies
      against different PKC isoforms. We identified one classic PKC isoform (alpha),
      three novel PKC isoforms (delta, epsilon, eta), and one atypical PKC isoform
      (zeta) in the IMCD. Carbachol induced a cytosol-to-membrane translocation of the
      PKC-eta isoform but did not alter the distribution of any other isoform. In
      contrast, AVP had no effect on the distribution of any PKC isoform tested. These
      data, taken together, demonstrate that carbachol is an activator of the
      phosphoinositide hydrolysis pathway in IMCD but do not demonstrate signaling via
      this pathway in response to AVP or DDAVP. These results suggest that the
      previously observed AVP-stimulated Ca2+ mobilization in IMCD may be due to a
      mechanism other than activation of the phosphoinositide hydrolysis pathway.

PMID- 9530274
TI  - Nitroflurbiprofen, a new nonsteroidal anti-inflammatory, ameliorates structural
      injury in the remnant kidney.
AB  - Cyclooxygenase derivatives and nitric oxide (NO) may influence the pathogenesis
      of progressive nephropathies. We investigated the effect of nitroflurbiprofen
      (NOF), a NO-releasing nonsteroidal anti-inflammatory drug (NSAID) without
      gastrointestinal toxicity, in rats with 5/6 ablation (NX). The following four
      groups were studied: Sham, sham-operated rats; Sham + NOF, Sham receiving oral
      NOF two times daily; NX, rats subjected to NX; and NX + NOF, NX receiving NOF.
      NOF was barely detected in plasma but released the parent compound flurbiprofen.
      At 30 days, glomerular hydraulic pressure (PGC) was 76 +/- 3 mmHg in NX (52 +/- 1
      in Sham, P < 0.05). NOF slightly reduced PGC to 69 +/- 2 mmHg in NX + NOF (P >
      0.05 vs. NX). Glomerular volumes behaved similarly. At 60 days, tail cuff
      pressure was 152 +/- 6 mmHg, glomerulosclerosis index was 22.1 +/- 9.5, and
      interstitial fractional area was 9.9 +/- 1.2% in NX. NOF reduced these parameters
      to 137 +/- 4 mmHg, 3.5 +/- 0.7, and 6.4 +/- 0.8%, respectively (P < 0.05),
      without causing growth stunting or anemia. These beneficial effects could not be
      ascribed to NO donation and may reflect cyclooxygenase inhibition. This is the
      first evidence that chronic NSAID treatment may ameliorate progressive
      nephropathies.

PMID- 9530276
TI  - Identification of gene family of caspases in rat kidney and altered expression in
      ischemia-reperfusion injury.
AB  - In the present study, we demonstrate that rat kidney contains caspase activity
      that was markedly inhibited by specific peptide inhibitors of caspases but not by
      inhibitors of Ser, Cys, Asp, or metalloproteinases. Using primers based on the
      nucleotide sequence of known members of Ced-3/interleukin-1 beta-converting
      enzyme (ICE) family from human origin, we have identified by reverse
      transcription (RT) polymerase chain reaction (PCR) analyses that rat kidney
      transcribes the genes for caspase-1 (ICE), caspase-2 (Nedd2), caspase-3 (CPP32),
      and caspase-6 (Mch2). RT-PCR products, when subcloned and sequenced, provided
      full-length cDNAs for ICE (1,209 bp) and CPP32 (786 bp) and partial cDNA products
      for Mch2 (561 bp) and Nedd2 (811 bp). The sequence analysis of the caspase cDNAs
      showed conserved catalytic site QACRG as well as Asp cleavage site. Rat kidneys
      subjected to ischemia-reperfusion injury revealed differential expression of
      caspases with marked increase in CPP32 and ICE mRNA and proteins during
      reperfusion, transient increase in Nedd2 mRNA and proteins during ischemia and
      the early period of reperfusion, and little change in Mch2 expression during the
      ischemia or reperfusion period. The altered expression suggests that caspases may
      act in concert in a cascade and may play an important role in ischemic acute
      renal failure.

PMID- 9530275
TI  - Differential effects of ACE and AT1 receptor inhibition on chemoattractant and
      adhesion molecule synthesis.
AB  - Ureteral obstruction causes infiltration of the kidney by monocytes/macrophages.
      This infiltrate is significantly reduced by administration of an angiotensin
      converting enzyme (ACE) inhibitor but not by a specific angiotensin II type 1
      receptor (AT1 receptor) antagonist. Chemoattractants and cell surface adhesive
      molecules mediate monocyte/macrophage infiltration. Rats with unilateral ureteral
      obstruction (UUO) of 1, 3, or 5 days duration were untreated or given enalapril
      or SC-51316 in the drinking water. We measured the mRNA levels of monocyte
      chemoatactic peptide 1 (MCP-1), a chemoattractant, and levels of intercellular
      adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1), two
      cell surface adhesion proteins. MCP-1 mRNA increased significantly after 1 day of
      UUO and increased further through 5 days of UUO in the obstructed kidney. ICAM-1
      mRNA also increased significantly after 1 day but steadily declined through 5
      days of UUO in the obstructed kidney. VCAM-1 mRNA did not increase significantly
      until after 3 days of UUO and increased further through 5 days of obstruction.
      Enalapril or SC-51316 treatment had no significant effect on ICAM-1 mRNA levels.
      MCP-1 mRNA levels were reduced but remained significantly elevated. Enalapril
      significantly blunted the increase in VCAM-1 mRNA levels and VCAM-1 protein
      determined by immunocytochemistry; SC-51316 had no significant effect. Thus
      changes in VCAM-1 levels may account for the differential effect of enalapril and
      SC-51316 on monocyte/macrophage infiltration of the kidney during ureteral
      obstruction.

PMID- 9530277
TI  - Regulation of AE2 mRNA expression in the cortical collecting duct by acid/base
      balance.
AB  - AE2 mRNA and protein is expressed in several nephron segments, one of which is
      the cortical collecting duct (CCD). However, the distribution of AE2 among the
      different cell types of the CCD and the function of AE2 in the kidney are not
      known. The purpose of this study was to determine the distribution of AE2 mRNA
      among the three CCD cell types and to examine the effects of changes in acid/base
      balance on its expression. Following NH4Cl (acid) or NaHCO3 (base) loading of
      rabbits for approximately 18 h, CCD cells were isolated by immunodissection. AE2
      mRNA levels were determined by RT-PCR and were normalized for beta-actin levels.
      We found that CCD cells express high levels of AE2 mRNA (approximately 500
      copies/cell). AE2 mRNA levels were significantly higher in CCD cells originating
      from base-loaded than acid-loaded rabbits, with an average increase of 3.7 +/-
      1.07-fold. The effect of pH on AE2 mRNA levels was also tested directly using
      primary cultures of CCD cells. CCD cells incubated in acidic media expressed
      significantly lower levels of AE2 mRNA than those in normal or alkaline media.
      Experiments with isolated principal cells, alpha-intercalated cells, and beta
      intercalated cells (separated by fluorescence-activated cell sorting)
      demonstrated that AE2 mRNA levels are comparable in the three collecting duct
      cell subtypes and are similarly regulated by changes in acid/base balance. Based
      on these results, we conclude that adaptation to changes in extracellular H+
      concentration is accompanied by opposite changes in AE2 mRNA expression. The
      observations that AE2 mRNA is not expressed in a cell-type-specific manner and
      that changes in acid/base balance have similar effects on each CCD cell subtype
      suggest that AE2 might serve a housekeeping function rather than being the apical
      anion exchanger of beta-intercalated cells.

PMID- 9530278
TI  - Isolation and characterization of kidney-specific ClC-K1 chloride channel gene
      promoter.
AB  - The rat ClC-K1 chloride channel is a kidney-specific member of the ClC chloride
      channel family found exclusively in the thin ascending limb of Henle's loop in
      the kidney. To gain insight into the mechanism(s) of kidney-specific expression
      of ClC-K1, a genomic clone that contains the 5'-flanking region of the rat ClC-K1
      gene was isolated. A single transcription start site was located 84 bp upstream
      of the start codon. The sequence of the proximal 5'-flanking region contained an
      activator protein (AP)-3 site, a glucocorticoid-responsive element, several AP-2
      sites, and several E-boxes, but it lacked a TATA box. To functionally express the
      promoter, the approximately 2.5-kb pair 5'-flanking region was ligated to a
      luciferase reporter gene and transfected into inner medullary (IM) cells, a
      stable ClC-K1-expressing cell line derived from the inner medulla of simian virus
      40 transgenic mouse, and ClC-K1-nonexpressing cell lines. Luciferase activity was
      7-to 24-fold greater in IM cells than those in nonexpressing cell lines,
      suggesting that the approximately 2.5-kb fragment contained cis-acting regulatory
      elements for cell-specific expression of the ClC-K1 gene. Deletion analysis
      revealed that this cell-specific promoter activity in IM cells was still present
      in the construct containing 51 bp of the 5'-flanking region but was lost in the 
      29 construct, clearly demonstrating that the 22 bp from -51 to -30 have a major
      role in the cell-specific activity of the ClC-K1 promoter. These 22 bp consist of
      purine-rich sequence (GGGGAGGGG-GAGGGGAG), and gel-retardation analysis
      demonstrated the existence of a specific protein(s) binding to this element in IM
      cells. These results suggest that the novel purine-rich element may play a key
      role in the activity of the ClC-K1 gene promoter.

PMID- 9530279
TI  - Localization of the extracellular Ca2+/polyvalent cation-sensing protein in rat
      kidney.
AB  - We previously identified transcripts encoding a G protein-coupled, extracellular
      calcium/polyvalent cation-sensing receptor, RaKCaR, in rat kidney (D. Riccardi,
      J. Park, W.-S. Lee, G. Gamba, E. M. Brown, and S. C. Hebert. Proc. Natl. Acad.
      Sci. USA 92:131-135, 1994), which was proposed to provide the mechanism for
      modulating a variety of renal functions in response to changes in extracellular
      Ca2+ (E. M. Brown. In: Handbook of Physiology. Bethesda, MD: Am. Physiol. Soc.,
      1992, sect. 8, vol. 2, chapt. 39, p. 1841-1916; and S. C. Hebert. Kidney Int. 50:
      2129-2139, 1996). Here, we examine the cellular and regional distribution of
      receptor protein by immunofluorescence microscopy using a polyclonal antibody
      raised against a 22 amino acid region of the NH2 terminus of the receptor. The
      most intense fluorescence was seen at the basolateral border of cortical thick
      ascending limb cells. Basolateral staining for the receptor was also detected in
      medullary thick ascending limbs, in macula densa cells identified by costaining
      with antibody to brain nitric oxide synthase, NOS-B1, and in distal convoluted
      tubule cells distinguished by costaining for the apical thiazide-sensitive Na(+)
      Cl- cotransporter. Apical anti-RaKCaR staining was detected at the base of the
      brush border of proximal tubules with decreasing intensity from S1 to S3
      segments. In cortical collecting ducts, anti-RaKCaR staining was detected in
      some, but not all, type A intercalated cells identified by costaining with anti
      H(+)-ATPase and anti-AE1 Cl-/HCO3- exchanger antibodies. The present study
      demonstrates that RaKCaR protein is expressed in many different nephron segments
      and that the polarity of receptor expression varies with cell type along the
      nephron. These results suggest potential roles for the extracellular Ca2+/
      polyvalent cation-sensing receptor in responding to both circulating and urinary
      concentrations of divalent minerals and potentially other polyvalent cations
      (e.g., aminoglycoside antibiotics) to modulate nephron function.

PMID- 9530280
TI  - Documentation of angiotensin II receptors in glomerular epithelial cells.
AB  - Angiotensin II decreases glomerular filtration rate, renal plasma flow, and
      glomerular capillary hydraulic conductivity. Although angiotensin II receptors
      have been demonstrated in mesangial cells and proximal tubule cells, the presence
      of angiotensin II receptors in glomerular epithelial cells has not previously
      been shown. Previously, we have reported that angiotensin II caused an
      accumulation of cAMP and a reorganization of the actin cytoskeleton in cultured
      glomerular epithelial cells. Current studies were conducted to verify the
      presence of angiotensin II receptors by immunological and non-peptide receptor
      ligand binding techniques and to ascertain the activation of intracellular signal
      transduction in glomerular epithelial cells in response to angiotensin II.
      Confluent monolayer cultures of glomerular epithelial cells were incubated with
      angiotensin II, with or without losartan and/or PD-123,319 in the medium.
      Membrane vesicle preparations were obtained by homogenization of washed cells
      followed by centrifugation. Sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis of membrane proteins followed by multiscreen immunoblotting was
      used to determine the presence of angiotensin II receptor type 1 (AT1) or type 2
      (AT2). Angiotensin II-mediated signal transduction in glomerular epithelial cells
      was studied by measuring the levels of cAMP, using radioimmunoassay. Results
      obtained in these experiments showed the presence of both AT1 and AT2 receptor
      types in glomerular epithelial cells. Angiotensin II was found to cause an
      accumulation of cAMP in glomerular epithelial cells, which could be prevented
      only by simultaneous use of losartan and PD-123,319, antagonists for AT1 and AT2,
      respectively. The presence of both AT1 and AT2 receptors and an increase in cAMP
      indicate that glomerular epithelial cells respond to angiotensin II in a manner
      distinct from that of mesangial cells or proximal tubular epithelial cells. Our
      results suggest that glomerular epithelial cells participate in angiotensin II
      mediated control of the glomerular filtration barrier.

PMID- 9530281
TI  - Axial heterogeneity of sodium-bicarbonate cotransporter expression in the rabbit
      proximal tubule.
AB  - It is generally accepted that Na(HCO3)n cotransport is the most important
      mechanism mediating basolateral bicarbonate efflux in the early proximal tubule.
      The presence of basolateral Na(HCO3)n cotransport in the late proximal tubule (S3
      segment) and in the juxtamedullary S1 and S2 segments has been controversial. The
      renal sodium-bicarbonate cotransporter (NBC) has been recently cloned from rat
      (M. F. Romero, M. A. Hediger, E. L. Boulpaep, and W. F. Boron. J. Am. Soc.
      Nephrol. 7: 1259, 1996), salamander (M. F. Romero, M. A. Hediger, E. L. Boulpaep,
      and W. F. Boron. Nature 387: 409-413, 1997), and human (C. E. Burnham, H. Amlal,
      Z. Wang, G. E. Shull, and M. Soleimani. J. Biol. Chem. 272: 19111-19114, 1997).
      The localization of NBC in the kidney is unknown. The present study was designed
      to localize NBC mRNA expression in the rabbit proximal tubule. In situ
      hybridization studies were combined with functional studies of basolateral
      Na(HCO3)n cotransport in superficial and juxtamedullary S1, S2, and S3 segments
      of the rabbit proximal tubule. The results demonstrate that NBC mRNA is localized
      predominantly to the cortex, with less expression in the outer medulla. NBC
      expression was not detected in the inner medulla. The highest level of NBC mRNA
      is in the S1 proximal tubule. NBC is expressed at a low levels in the S3 segment,
      with intermediate expression in the S2 segment. In bicarbonate-buffered
      solutions, the rate of base efflux mediated by Na(HCO3)n cotransport followed a
      similar pattern in superficial and juxtamedullary proximal tubule segments, i.e.,
      S1 > S2 > S3. The juxtamedullary S1 segment had the greatest rate of basolateral
      Na(HCO3)n cotransport and the highest level of NBC expression in the proximal
      tubule.

PMID- 9530282
TI  - 1998 study guide. Brain injury rehabilitation, pain rehabilitation.

PMID- 9530283
TI  - Different DNA polymerases are involved in the short- and long-patch base excision
      repair in mammalian cells.
AB  - Mammalian cells possess two distinct pathways for completion of base excision
      repair (BER): the DNA polymerase beta (Pol beta)-dependent short-patch pathway
      (replacement of one nucleotide), which is the main route, and the long-patch
      pathway (resynthesis of 2-6 nucleotides), which is PCNA-dependent. To address the
      issue of how these two pathways share their role in BER the ability of Pol beta
      defective mammalian cell extracts to repair a single abasic site constructed in a
      circular duplex plasmid molecule was tested in a standard in vitro repair
      reaction. Pol beta-deficient extracts were able to perform both BER pathways.
      However, in the case of the short-patch BER, the repair kinetics was
      significantly slower than with Pol beta-proficient extracts, while the efficiency
      of the long-patch synthesis was unaffected by the loss of Pol beta. The repair
      synthesis was fully dependent on PCNA for the replacement of long patches. These
      data give the first evidence that in cell extracts DNA polymerases other than Pol
      beta are specifically involved in the long-patch BER. These DNA polymerases are
      also able to perform short-patch BER in the absence of PCNA, although less
      efficiently than Pol beta. These findings lead to a novel model whereby the two
      BER pathways are characterized by different protein requirements, and a
      functional redundancy at the level of DNA polymerases provides cells with backup
      systems.

PMID- 9530284
TI  - A Mn(II)-Mn(III) EPR signal arises from the interaction of NO with the S1 state
      of the water-oxidizing complex of photosystem II.
AB  - It was shown recently [Goussias, C., Ioannidis, N., and Petrouleas, V. (1997)
      Biochemistry 36, 9261-9266] that incubation of photosystem II preparations with
      NO at -30 degrees C in the dark results in the formation of a new intermediate of
      the water-oxidizing complex. This is characterized by an EPR signal centered at g
      = 2 with prominent manganese hyperfine structure. We have examined the detailed
      structure of the signal using difference EPR spectroscopy. This is facilitated by
      the observations that NO can be completely removed without decrease or
      modification of the signal, and illumination at 0 degree C eliminates the signal.
      The signal spans 1600 G and is characterized by sharp hyperfine structure. 14NO
      and 15NO cw EPR combined with pulsed ENDOR and ESEEM studies show no detectable
      contributions of the nitrogen nucleus to the spectrum. The spectrum bears
      similarities to the experimental spectrum of the Mn(II)-Mn(III) catalase [Zheng,
      M., Khangulov, S. V., Dismukes, G. C., and Barynin, V. V. (1994) Inorg. Chem. 33,
      382-387]. Simulations allowing small variations in the catalase-tensor values
      result in an almost accurate reproduction of the NO-induced signal. This presents
      strong evidence for the assignment of the latter to a magnetically isolated
      Mn(II)-Mn(III) dimer. Since the starting oxidation states of Mn are higher than
      II, we deduce that NO acts effectively as a reductant, e.g., Mn(III)-Mn(III) + NO
      -> Mn(II)-Mn(III) + NO+. The temperature dependence of the nonsaturated EPR
      signal intensity in the range 2-20 K indicates that the signal results from a
      ground state. The cw microwave power saturation data in the range 4-8 K can be
      interpreted assuming an Orbach relaxation mechanism with an excited state at
      delta = 42 K. Assuming antiferromagnetic coupling, -2JS1.S2, between the two
      manganese ions, J is estimated to be 10 cm-1. The finding that an EPR signal from
      the Mn cluster of PSII can be clearly assigned to a magnetically isolated Mn(II)
      Mn(III) dimer bears important consequences in interpreting the structure of the
      Mn cluster. Although the signal is not currently assigned to a particular S
      state, it arises from a state lower than S1, possibly lower than S0, too.

PMID- 9530285
TI  - Peptide design aided by neural networks: biological activity of artificial signal
      peptidase I cleavage sites.
AB  - De novo designed signal peptidase I cleavage sites were tested for their
      biological activity in vivo in an Escherichia coli expression and secretion
      system. The artificial cleavage site sequences were generated by two different
      computer-based design techniques, a simple statistical method, and a neural
      network approach. In previous experiments, a neural network was used for feature
      extraction from a set of known signal peptidase I cleavage sites and served as
      the fitness function in an evolutionary design cycle leading to idealized
      cleavage site sequences. The cleavage sites proposed by the two algorithms were
      active in vivo as predicted. There seems to be an interdependence between several
      cleavage site features for the constitution of sequences recognized by signal
      peptidase. It is concluded that neural networks are useful tools for sequence
      oriented peptide design.

PMID- 9530287
TI  - Critical analysis of coronary artery bypass graft surgery: a 30-year journey.

PMID- 9530286
TI  - HIV-1 protease inhibitors are substrates for the MDR1 multidrug transporter.
AB  - The FDA approved HIV-1 protease inhibitors, ritonavir, saquinavir, and indinavir,
      are very effective in inhibiting HIV-1 replication, but their long-term efficacy
      is unknown. Since in vivo efficacy depends on access of these drugs to
      intracellular sites where HIV-1 replicates, we determined whether these protease
      inhibitors are recognized by the MDR1 multidrug transporter (P-glycoprotein, or P
      gp), thereby reducing their intracellular accumulation. In vitro studies in
      isolated membrane preparations from insect cells infected with MDR1-expressing
      recombinant baculovirus showed that these inhibitors significantly stimulated P
      gp-specific ATPase activity and that this stimulation was inhibited by SDZ PSC
      833, a potent inhibitor of P-gp. Furthermore, photoaffinity labeling of P-gp with
      the substrate analogue [125I]iodoarylazidoprazosin (IAAP) was inhibited by all
      three inhibitors. Cell-based approaches to evaluate the ability of these protease
      inhibitors to compete for transport of known P-gp substrates showed that all
      three HIV-1 protease inhibitors were capable of inhibiting the transport of some
      of the known P-gp substrates but their effects were generally weaker than other
      documented P-gp modulators such as verapamil or cyclosporin A. Inhibition of HIV
      1 replication by all three protease inhibitors was reduced but could be restored
      by MDR1 inhibitors in cells expressing MDR1. These results indicate that the HIV
      1 protease inhibitors are substrates of the human multidrug transporter,
      suggesting that cells in patients that express the MDR1 transporter will be
      relatively resistant to the anti-viral effects of the HIV-1 protease inhibitors,
      and that absorption, excretion, and distribution of these inhibitors in the body
      may be affected by the multidrug transporter.

PMID- 9530288
TI  - The development of interventional cardiology.

PMID- 9530289
TI  - Revascularization: reflections of a clinician.

PMID- 9530290
TI  - The future of research in genitourinary radiology: through the looking glass--a
      view from the Society of Uroradiology.

PMID- 9530291
TI  - A commentary on the past and a look at the future of genitourinary imaging.

PMID- 9530292
TI  - MR imaging for assessment of gastric motility disorders: has its time come?

PMID- 9530293
TI  - Pulmonary digital subtraction angiography: ready for prime time.

PMID- 9530294
TI  - Pneumatosis intestinalis: a review.
AB  - This review illustrates the changing paradigms in the understanding of the
      pathogenesis of pneumatosis intestinalis. Although many theories have been
      evoked, pragmatically there appear to be four major clinical and diagnostic
      imaging considerations. The most common and most emergent life-threatening cause
      of intramural bowel gas is the result of bowel necrosis due to bowel ischemia,
      infarction, necrotizing enterocolitis, neutropenic colitis, volvulus, and sepsis.
      In the stomach, intramural gas can be caused by emphysematous gastritis or
      ingestion of caustic agents. These situations represent surgical emergencies.
      Pneumatosis is found secondary to mucosal disruption presumably due to over
      distention from peptic ulcer, pyloric stenosis, annular pancreas, and even to
      more distal obstruction. Disruption can also be caused by ulceration, erosions,
      or trauma, including the trauma of child abuse. Disruption can also be iatrogenic
      from intracatheter jejunal feeding tubes, stent perforation, sclerotherapy, or
      surgical or endoscopic trauma. In these cases, the gas may be focal or linear.
      Treatment depends on the extent of the disruption and the underlying cause. A
      more subtle form of mucosal disruption may occur due to mucosal erosions and also
      to defects in intestinal crypts secondary to acute and subclinical enteritides
      that allow intraluminal bacterial gas under pressure to percolate into the bowel
      wall layers, particularly the submucosa (29). Pneumatosis, often linear or cystic
      in appearance, is seen with increased frequency in patients who are
      immunocompromised because of steroids, chemotherapy, radiation therapy, or AIDS.
      In these cases, the pneumatosis may result from intraluminal bacterial gas
      entering the bowel wall due to increased mucosal permeability caused by defects
      in bowel wall lymphoid tissue. Clinical and imaging findings are important in the
      differentiation of this transient pneumatosis from fulminant life-threatening
      causes in this subset of patients. A pulmonary cause must still be considered in
      cases of chronic obstructive pulmonary disease, asthma, and cystic fibrosis. It
      can occur with barotrauma and after chest tube placement. It may relate to
      increased intrathoracic pressure associated with retching and vomiting. The
      possibility remains that occasionally the origin of pneumatosis intestinalis will
      remain cryptogenic--caused but unexplained.

PMID- 9530295
TI  - Half-Fourier RARE MR cholangiopancreatography: experience in 300 subjects.
AB  - PURPOSE: To determine prospectively the clinical applications and diagnostic
      accuracy of half-Fourier rapid acquisition with relaxation enhancement (RARE)
      magnetic resonance (MR) cholangiopancreatography (MRCP) in a large patient
      population. MATERIALS AND METHODS: Breath-hold, heavily T2-weighted half-Fourier
      RARE MRCP was performed in 265 patients with suspected pancreaticobiliary disease
      and in 35 control patients without symptoms or signs referrable to the biliary
      tract or pancreatic duct. MRCP findings were correlated with those at direct
      cholangiography, pathologic examination, cross-sectional imaging, and clinical
      follow-up. RESULTS: Diagnostic MRCP examinations were obtained in 299 (99.7%)
      subjects. MRCP yielded an accuracy of 100% in determining the presence of
      pancreaticobiliary disease, the presence and level of biliary obstruction, and
      obstruction due to bile duct calculi. The accuracy of MRCP and MR imaging in
      determining the presence and level of malignant obstruction was 98.2%. MRCP
      obviated endoscopic retrograde cholangiopancreatography (ERCP) by excluding
      choledocholithiasis in patients with acute pancreatitis (n = 13) and nonspecific
      abdominal pain (n = 82). In patients with sclerosing cholangitis and acquired
      immunodeficiency syndrome cholangiopathy, MRCP depicted the biliary tract as
      clearly as did ERCP (n = 9). After failed ERCP, MRCP delineated the
      pancreaticobiliary tract and helped determine therapeutic options (n = 27).
      CONCLUSION: Half-Fourier RARE MRCP enables accurate evaluation of
      pancreaticobiliary disease and obviates ERCP in some patients.

PMID- 9530296
TI  - Gastric emptying and motility: assessment with MR imaging--preliminary
      observations.
AB  - PURPOSE: To evaluate a magnetic resonance (MR) imaging method for simultaneous
      assessment of gastric emptying and motility. MATERIALS AND METHODS: Gastric
      emptying and motility were measured in nine volunteers after ingestion of a
      liquid meal. A specially designed MR imaging protocol was used that allowed
      simultaneous assessment of gastric emptying (spatial resolution, 1.5 mm;
      corrected for gastric secretion volume) and gastric motility (temporal
      resolution, 1.2 seconds; spatial resolution, 3.1 mm). To evaluate the ability to
      detect small changes in gastric motor activity with findings from this method,
      the influence of a prokinetic agent (loxiglumide) on gastric emptying and
      motility was tested in five volunteers. RESULTS: Each contraction could be
      individually visualized at MR imaging. Administration of loxiglumide resulted in
      decreased gastric half-emptying time (mean +/- 1 standard error of the mean, 88.1
      minutes +/- 6.3 for the placebo and 39.1 minutes +/- 6.7 for loxiglumide) and
      increased gastric motility (contraction frequency, 2.26 contractions per minute
      +/- 0.15 for the placebo and 3.04 per minute +/- 0.04 for loxiglumide).
      CONCLUSION: MR imaging makes it feasible to study gastric emptying and gastric
      motility and to determine the influence of drugs on gastric motor activity.

PMID- 9530297
TI  - Biliary tract carcinoma complicating primary sclerosing cholangitis: evaluation
      with CT, cholangiography, US, and MR imaging.
AB  - PURPOSE: To assess the value of computed tomography (CT), cholangiography,
      ultrasonography (US), and magnetic resonance (MR) imaging in the demonstration of
      biliary tract carcinoma complicating primary sclerosing cholangitis (PSC).
      MATERIALS AND METHODS: Thirty patients were studied who had PSC and biliary tract
      carcinoma. Twenty-six patients had cholangiocarcinoma, and four had gallbladder
      carcinoma. Sixty-four CT scans, 41 cholangiograms, 40 US studies, and seven MR
      studies were reviewed retrospectively for evidence of tumor and PSC. Imaging
      results were correlated with pathologic findings from whole liver specimens and
      biopsies. Presence of mass was rated as definite, probable, possible, or doubtful
      or absent. RESULTS: On CT scans, cholangiocarcinomas produced hypoattenuating
      masses in 17 of 23 cases, delayed contrast enhancement in six of 12, progressive
      biliary dilatation in five of 15, and thickened bile duct wall in two of 23. On
      cholangiograms, dominant strictures were present in 18 of 21 cases of
      cholangiocarcinoma; 13 were malignant, and five were benign. Cholangiocarcinoma
      formed polypoid bile duct masses in two of 21 cases. Biliary dilatation was
      caused by cholangiocarcinoma in 10 of 12 cases and by benign stricture in two.
      Gallbladder carcinomas demonstrated masses on CT scans, cholangiograms, and US
      images, and wall thickening on CT and US images. Overall, definite or probable
      tumor was demonstrated in 25 of 30 patients (83%). CONCLUSION: Most biliary tract
      carcinomas complicating PSC can be demonstrated on imaging studies.

PMID- 9530298
TI  - Hepatic hemangioma: quantitative color power US angiography--facts and fallacies.
AB  - PURPOSE: To explore the origin of signals detected with color power ultrasound
      (US) angiography (CPA) and evaluate a semiquantitative method to assess signals
      in hepatic hemangiomas. MATERIALS AND METHODS: Twenty-four adult patients with 27
      hepatic hemangiomas (< 2 cm in diameter) and five patients with five hyperechoic
      hepatic metastases underwent CPA and conventional color Doppler US in this
      prospective study. A sponge phantom was studied to determine whether the origin
      of CPA signals was related to architecture. The mean number of signals and the
      signal density in each lesion were scored. RESULTS: A "diffuse blush" was seen in
      all capillary hemangiomas at CPA, whereas no signal was seen at color Doppler US.
      The sponge phantom test produced a CPA appearance similar to that of capillary
      hemangiomas. Quantitative analysis of CPA images of hepatic hemangiomas showed a
      mean of 16.1 signals per cubic centimeter and a mean signal area of 25%.
      Hyperechoic avascular hepatic metastases resulted in CPA images similar to those
      of hepatic hemangiomas, with no quantitative difference in signal count, despite
      a mild qualitative difference at CPA. CONCLUSION: CPA signals in hepatic
      hemangiomas appear to be related more to architecture than to true capillary
      flow. There is a qualitative difference in the strength of the blush at CPA
      between hepatic hemangiomas and metastases, which may be the only possible
      differentiating factor.

PMID- 9530299
TI  - Detection of mass lesions with MR colonography: preliminary report.
AB  - PURPOSE: To evaluate the performance of magnetic resonance (MR) colonography in
      the detection of colorectal mass lesions. MATERIALS AND METHODS: Twenty-three
      patients underwent MR colonography preceding colonoscopy. The colon was filled
      with a gadolinium-water mixture (1:100) with MR imaging guidance, and the patient
      was imaged prone and supine with a breath-hold three-dimensional spoiled gradient
      recalled sequence. In addition, two-dimensional spoiled gradient-recalled images
      were acquired before and after intravenous administration of gadopentetate
      dimeglumine. Images were interactively analyzed on the basis of multiplanar
      reconstruction by two radiologists. For regions that were not conclusively
      assessable with multiplanar reconstruction, virtual intraluminal endoscopic
      images of the colon were reconstructed. MR findings were correlated with
      colonoscopic results. RESULTS: Two patients were excluded from the analysis.
      Findings in eight of 11 patients were correctly assessed as normal and in six of
      10 as mass-positive. In the four patients with false-negative findings, one had
      two 8-mm polyps and the other three had polyps smaller than 5 mm. All nine mass
      lesions larger than 10 mm, as well as four of the 10 polyps ranging between 5 and
      10 mm, were detected, but all polyps smaller than 5 mm were missed. In contrast
      to the polyps less than 5 mm, the four missed polyps (5-10 mm) could be
      identified retrospectively on virtual intraluminal endoscopic images. Contrast
      enhancement was documented in 13 polyps. CONCLUSION: Three-dimensional MR
      colonography provided virtual colonoscopic viewing and helped detection of
      colonic polyps.

PMID- 9530300
TI  - Pseudolesions at T1-weighted gradient-echo imaging after administration of
      superparamagnetic iron oxide: comparison with portal perfusion abnormalities at
      CT during arterial portography.
AB  - PURPOSE: To compare specific findings at T1-weighted gradient-echo (GRE) magnetic
      resonance (MR) imaging performed after administration of superparamagnetic iron
      oxide (SPIO) with nontumorous regional portal perfusion abnormalities seen at
      computed tomography (CT) during arterial portography (CTAP). MATERIALS AND
      METHODS: The results of CTAP, MR imaging, and surgery were compared in 19
      patients with liver metastases and five with benign liver tumors. MR imaging was
      performed by using turbo spin-echo (SE) sequences and a GRE sequence before and
      after infusion of SPIO. RESULTS: At CTAP, 34 nontumorous portal perfusion defects
      ("straight line sign," pseudolesions) were seen. After intravenous administration
      of SPIO, 18 nontumorous signal intensity differences were seen on T1-weighted GRE
      images in corresponding locations. No corresponding nontumorous signal intensity
      differences were seen on unenhanced MR images. The mean signal-to-noise ratio on
      the SPIO-enhanced GRE images was reduced from 26.3 to 16.6 in the areas of
      nontumorous signal intensity differences, whereas that in areas of normal portal
      perfusion (normal CTAP findings) was reduced to 10.2. CONCLUSION: Impaired portal
      perfusion decreased the uptake of SPIO in histopathologically normal regions of
      liver parenchyma. Resultant differences in signal intensity were better
      visualized on GRE than on turbo SE images.

PMID- 9530301
TI  - Hepatic cryoablation: US monitoring of extent of necrosis in normal pig liver.
AB  - PURPOSE: To determine the accuracy of ultrasonography (US) for prediction of
      hepatic tissue necrosis after cryoablation in normal pig liver. MATERIALS AND
      METHODS: Five normal pig livers were treated with cryoablation monitored with US.
      After a single freeze cycle at 50% flow capacity, the widest diameter of the
      cryolesion was identified and marked with wire placement (22 wires in five
      lesions). Livers were removed 24 hours later, and wire tracks were marked with
      India ink. Livers were sectioned, and the distance was measured between wire
      tracks and tissue necrosis caused by freezing. RESULTS: The mean volume of areas
      of tissue necrosis was 11.6 cm3 +/- 4.0, the mean diameter was 2.9 cm +/- 1.0,
      and the mean maximum diameter was 2.9 cm +/- 0.7. The mean distance between the
      edge of necrosis and the wire track was 1.1 mm +/- 1.4. By excluding one outlier
      (6.5 mm), the mean distance from the ice ball to the necrotic area was 0.8 mm +/-
      0.8. Uniform necrosis of hepatic parenchyma within the cryolesion was confirmed.
      CONCLUSION: US can be used to predict reliably the size of the necrotic area
      after hepatic cryoablation in normal pig liver. Knowledge of a small but
      consistent underestimation of tissue necrosis is important when planning
      cryoablation.

PMID- 9530302
TI  - Posterior lobe of the pituitary gland: correlation between signal intensity on T1
      weighted MR images and vasopressin concentration.
AB  - PURPOSE: To correlate the signal intensity on magnetic resonance (MR) images in
      the posterior lobe of the pituitary gland with the vasopressin content. MATERIALS
      AND METHODS: Fourteen rabbits were studied: 12 water-deprived rabbits (two each
      at 48, 74, 96, 120, 144, or 168 hours of deprivation) and two control rabbits.
      Sagittal T1-weighted MR images were obtained before and after water deprivation.
      The signal intensity ratio of the posterior lobe to the pons was correlated with
      the vasopressin content in the posterior lobe, which was measured by means of
      radioimmunoassay. RESULTS: Before water deprivation, high signal intensity in the
      posterior lobe was demonstrated clearly in all rabbits. The signal intensity
      ratio and vasopressin content in the posterior lobe gradually decreased with
      water deprivation. The signal intensity ratio correlated strongly with the
      vasopressin content in the posterior lobe (Pearson correlation coefficient, .809;
      P < .001). CONCLUSION: The signal intensity ratio on T1-weighted MR images may be
      used as an indicator for the quantitative evaluation of the vasopressin content
      in the posterior lobe. The results strongly suggest that the origin of the high
      signal intensity in the posterior lobe on T1-weighted MR images is the
      vasopressin-neurophysin II-copeptin complex.

PMID- 9530303
TI  - Cerebrovascular disease risk factors: neuroradiologic findings in patients with
      activated protein C resistance.
AB  - PURPOSE: To assess the patterns of abnormal neuroradiologic findings in patients
      with a hypercoagulable state related to activated protein C (APC) resistance.
      MATERIALS AND METHODS: Records in 23 patients with a hypercoagulable state
      related to APC resistance (18 women, five men; average age, 44.5 years) were
      reviewed for cerebrovascular disease risk factors and other causes of a
      hypercoagulable state. Computed tomographic scans, magnetic resonance (MR)
      images, angiograms, and transesophageal echocardiograms were also reviewed.
      RESULTS: Stroke risk factors or other causes of a hypercoagulable state were
      found in 12 patients. Arterial infarcts were seen in 18 patients. Hyperintense
      white matter foci were seen on MR images in six patients. Dural sinus thrombosis
      was found in four patients. Angiograms of intracranial circulation in six
      patients showed major artery occlusions in four. MR angiograms in four patients
      showed internal carotid artery occlusion in one. No major abnormalities were seen
      in extracranial cerebral vasculature in 15 patients. Transesophageal
      echocardiograms in 11 patients showed a patent foramen ovale in one patient but
      no systemic source of embolism. Seven patients had non-central nervous system
      thrombotic events. CONCLUSION: Patients with APC resistance and stroke appear to
      differ from the general stroke population in terms of age and frequency of
      extracranial sources of cerebrovascular disease.

PMID- 9530305
TI  - Circle of Willis: morphologic variation on three-dimensional time-of-flight MR
      angiograms.
AB  - PURPOSE: To establish normal reference values for the presence of the anatomic
      variants of the circle of Willis and average diameters for its component vessels
      by using three-dimensional time-of-flight magnetic resonance (MR) angiography and
      to determine whether age- or sex-related differences exist in the circle's
      anatomy. MATERIALS AND METHODS: One hundred fifty volunteers were grouped
      according to age: those aged 20-25 years (n = 50) and those aged 60-88 years (n =
      100). All subjects underwent three-dimensional time-of-flight MR angiography of
      the arterial circle at 1.5 T. The anatomic variants of the anterior and posterior
      parts of the circle were determined separately, the completeness of the entire
      circle was assessed, and the diameters of all component vessels were measured.
      RESULTS: On MR angiograms, 111 (74%) subjects demonstrated a complete anterior
      part of the circle, 78 (52%) demonstrated a complete posterior part of the
      circle, and 63 (42%) demonstrated an entirely complete circle of Willis (complete
      anterior and posterior parts of the circle combined). The presence of an entirely
      complete circle of Willis was slightly higher in younger persons and in women.
      Most vessel diameters were smaller in women, except for the diameter of the
      posterior communicating artery. Statistically significant differences were found
      in vessel diameters between the younger and the older age groups. CONCLUSION: The
      authors determined normal reference values for morphologic variants and diameter
      measurements of the circle of Willis specific to three dimensional time-of-flight
      MR angiography.

PMID- 9530306
TI  - Acute occlusion of the middle cerebral artery: early evaluation with triphasic
      helical CT--preliminary results.
AB  - PURPOSE: To evaluate use of triphasic helical computed tomography (CT) for early
      diagnosis of occlusion and assessment of ischemia in cases of acute middle
      cerebral arterial occlusion. MATERIALS AND METHODS: Thirty-five patients with
      acute ischemia underwent triphasic helical CT within 6 hours after symptom onset.
      Early arterial, perfusion, and delayed phase CT scans were obtained 18, 30, and
      80 seconds, respectively, after contrast material administration. Eighteen
      patients had proximal middle cerebral arterial occlusion diagnosed at magnetic
      resonance (MR) or digital subtraction angiography. Follow-up CT or MR imaging was
      performed in all patients. Two independent observers interpreted images for signs
      of arterial occlusion, collateral vessels, and the ischemic zone. RESULTS: One
      observer found at least one of three signs in 17 of the 18 patients with
      occlusion, and the other found at least one sign in all 18: Early decreased
      arterial contrast enhancement was seen by both observers in 11 patients (kappa =
      0.77), a nonenhancing arterial segment was seen by the two observers in 12 and 14
      (kappa = 0.73), and delayed asymmetric arterial enhancement was seen in 13 and 16
      (kappa = 0.49). Triphasic CT findings of the ischemic zone were consistent with
      follow-up CT or MR imaging findings in seven of 12 patients. CONCLUSION:
      Triphasic helical CT is useful for early diagnosis of acute proximal middle
      cerebral arterial occlusion and assessment of the ischemic zone.

PMID- 9530304
TI  - Alzheimer disease: quantitative H-1 MR spectroscopic imaging of frontoparietal
      brain.
AB  - PURPOSE: To replicate previous hydrogen-1 magnetic resonance (MR) spectroscopic
      imaging findings of metabolic abnormalities in patients with Alzheimer disease
      (AD), to verify that metabolic abnormalities are not an artifact of structural
      variations measured at MR imaging, to determine whether metabolic changes
      correlate with dementia severity, and to test whether MR imaging and MR
      spectroscopic imaging findings together improve ability to differentiate AD.
      MATERIALS AND METHODS: MR spectroscopic imaging and MR imaging were performed in
      28 patients with AD and 22 healthy elderly subjects. Spectroscopic imaging data
      were coregistered with MR imaging segmentation data to obtain volume-corrected
      metabolite concentrations. RESULTS: Consistent with previous results, N-acetyl
      aspartate (NAA) levels were statistically significantly reduced in frontal and
      posterior mesial cortex of AD patients, presumably due to neuronal loss. NAA
      level reductions were independent of structural variations measured at MR imaging
      and, in parietal mesial cortex, were correlated mildly with dementia severity.
      Spectroscopic imaging findings of NAA level combined with MR imaging measures did
      not improve discrimination power for AD relative to that of MR imaging alone.
      CONCLUSION: Reduced NAA levels in frontoparietal brain are of limited use for
      diagnosis of AD. However, they are not an artifact of structural variations and
      thus may provide useful information for the understanding of the pathologic
      processes underlying AD.

PMID- 9530307
TI  - Comparison of CT and MR imaging in staging of neck metastases.
AB  - PURPOSE: To compare the abilities of magnetic resonance (MR) imaging and computed
      tomography (CT) in detection of lymph node metastasis from head and neck squamous
      cell carcinoma. MATERIALS AND METHODS: MR imaging and CT were performed with
      standard protocols in patients with known carcinoma of the oral cavity,
      oropharynx, hypopharynx, or larynx. Histopathologic examination was performed to
      validate imaging findings. Between 1991 and 1994, 213 patients undergoing 311
      neck dissections were accrued at three institutions. RESULTS: For the upper
      jugular and spinal accessory regions, the areas under the receiver operating
      characteristic curves for combined information on size and internal abnormality
      were 0.80 for CT and 0.75 for MR imaging. Sensitivities, specificities, negative
      predictive values (NPVs), and positive predictive values (PPVs) were calculated
      for various size criteria with and without internal abnormality information. With
      use of a 1-cm size or an internal abnormality to indicate a positive node, CT had
      an NPV of 84% and a PPV of 50%, and MR imaging had an NPV of 79% and a PPV of
      52%. CT achieved an NPV of 90%, correlating with a PPV of 44%, with use of 5-mm
      size as an indicator of a positive node. CONCLUSION: CT performed slightly better
      than MR imaging for all interpretative criteria. However, a high NPV was achieved
      only when a low size criterion was used and was therefore associated with a
      relatively low PPV.

PMID- 9530308
TI  - Possible pulmonary embolus: evaluation with digital subtraction versus cut-film
      angiography--prospective study in 80 patients.
AB  - PURPOSE: To determine whether intraarterial digital subtraction angiography (DSA)
      is as accurate as cut-film (film hard-copy) angiography (CFA) in the evaluation
      of suspected pulmonary embolus. MATERIALS AND METHODS: Under a protocol approved
      by the institutional review board, CFA and DSA images were obtained in identical
      posteroanterior and oblique projections in one lung of each patient undergoing
      pulmonary angiography (n = 80). Diagnoses based on results of blinded review of
      each study (CFA vs DSA) by three separate reviewers (80 patients x three
      reviewers = 240 diagnoses for each modality) were compared with the diagnoses
      made by the physician who performed the procedure on the basis of CFA, DSA, and
      clinical data and with the consensus diagnoses obtained by means of group review
      of both studies together if necessary. The reviewers' confidence in their
      diagnoses was graded from 1 (certain) to 10 (uncertain). RESULTS: Pulmonary
      emboli were present in 13 (16%) of 80 patients. Two hundred thirty-six (98.3%) of
      240 DSA diagnoses and 231 (96.3%) of 240 CFA diagnoses were correct. The
      sensitivity (correct identification of emboli by all three reviewers) of DSA was
      92% and of CFA was 69% (P = .083). The specificities of the modalities were not
      statistically significantly different. The reviewers' confidence was
      significantly better in their DSA diagnoses than in their CFA diagnoses (P <
      .004). CONCLUSION: DSA allows more confident detection of pulmonary embolus than
      does CFA, with no loss in diagnostic accuracy.

PMID- 9530309
TI  - Pulmonary embolism: comparison of cut-film and digital pulmonary angiography.
AB  - PURPOSE: To compare "cut-film" (film hard-copy) angiography (CFA) with digital
      pulmonary angiography in the detection of pulmonary embolism (PE). MATERIALS AND
      METHODS: Thirty-six adult patients (39 lungs) underwent selective digital
      pulmonary angiography for suspected PE. Imaging was repeated in one selected
      projection by using cut film. The standard was consensus interpretation of both
      CFA and digital angiographic images and clinical course. Three vascular
      radiologists subsequently reviewed the digital and cut-film images in a blinded
      fashion and ranked the likelihood of the presence of PE on a five-point scale.
      The two modalities were compared by means of receiver operating characteristic
      (ROC) analysis. Image quality (i.e., sharpness, opacification of subsegmental
      vessels, and exposure) was judged on a three-point scale. The highest-order
      pulmonary artery branch seen on each study was recorded. RESULTS: ROC curve
      analyses for all three operators showed similar diagnostic performance for
      digital pulmonary angiography and CFA, with one operator showing better
      performance with digital subtraction angiography than with CFA (P = .04).
      Compared with the final diagnosis, single-plane digital pulmonary angiography had
      higher sensitivity for the detection of PE than had CFA. The specificity was 100%
      for both modalities. The mean score in patients with findings positive for PE was
      higher in the digital pulmonary angiography group than in the CFA group (P <
      .005). There was no difference in the mean score in patients who did not have a
      PE. There also was no difference in the smallest detectable subsegmental branch
      (P = .87) or in the average estimate of image quality. CONCLUSION: Selective
      digital pulmonary angiography and CFA offer similar diagnostic performance and
      image quality. Digital pulmonary angiography is a reasonable alternative to CFA
      in the diagnosis of PE.

PMID- 9530310
TI  - Recurrent gastrointestinal bleeding: use of thrombolysis with anticoagulation in
      diagnosis.
AB  - PURPOSE: To determine the safety and diagnostic accuracy of a provocative
      protocol with heparin and urokinase to induce bleeding and determine the source
      in patients with chronic gastrointestinal hemorrhage. MATERIALS AND METHODS: Nine
      patients had gastrointestinal bleeding from an indeterminate source and had
      negative results from esophagogastroduodenoscopy, colonoscopy, small-bowel
      examination, and angiography. Ten provocative bleeding studies were performed
      prospectively. Patients had no clinical evidence of bleeding within 2 days before
      the study. Intravenous administration of heparin and urokinase was performed
      systemically during a 4-hour period while scintigraphy was performed
      continuously. Mesenteric angiography was performed immediately in patients in
      whom substantial gastrointestinal bleeding was detected at scintigraphy. RESULTS:
      The provocative protocol was successful in inducing scintigraphically detectable
      hemorrhage in four (40%) studies within 4 hours. In two of these four studies,
      the source of hemorrhage was determined and treated with embolization or surgery.
      Three (30%) studies demonstrated scintigraphic evidence of hemorrhage only at
      delayed imaging (8-24 hours after initiation of the study). The remaining three
      (30%) studies did not show active bleeding. No complications occurred, including
      hemodynamic instability or uncontrollable decreases in hematocrit. CONCLUSION:
      Since this protocol with heparin and urokinase enabled determination of the
      bleeding source in only two of 10 studies, protocol modifications are necessary
      before this intervention is used widely.

PMID- 9530312
TI  - Hemodialysis access stenosis: early detection with color Doppler US.
AB  - PURPOSE: To evaluate color Doppler ultrasound (US) in detection of subclinical
      stenosis of hemodialysis access grafts and fistulas. MATERIALS AND METHODS:
      Doppler US was performed in 40 consecutive patients with no clinical or
      laboratory findings of hemodialysis access dysfunction. To assess the presence
      and percentage of stenosis, the maximum systolic blood velocity and velocity
      ratios were measured and the US images were assessed visually. Fistulography was
      recommended in patients who demonstrated stenosis greater than 50% at US.
      RESULTS: At US, 32 of the 40 patients had evidence of stenosis greater than 50%.
      In 23 of the 32 patients, a follow-up fistulogram was obtained. Hemodynamically
      significant stenosis was confirmed in 19 of the 23 patients at fistulography.
      Percutaneous transluminal angioplasty was then performed in 18 of the 19 patients
      and was successful. CONCLUSION: Color Doppler US is more sensitive than clinical
      or laboratory methods for detection of hemodialysis access stenosis. Screening
      with US appears to enable earlier detection and therapy.

PMID- 9530311
TI  - Vascular complications of liver transplantation: evaluation with gadolinium
      enhanced MR angiography.
AB  - PURPOSE: To evaluate use of gadolinium-enhanced magnetic resonance (MR)
      angiography in detection of vascular complications of liver transplantation.
      MATERIALS AND METHODS: Thirteen liver transplant recipients suspected to have
      vascular complications were evaluated with gadolinium-enhanced MR angiography by
      using a three-dimensional spoiled gradient-echo breath-hold technique during the
      arterial and venous phases of a high-dose (42 mL) bolus injection of gadolinium
      contrast material. Conventional angiography (n = 11) and surgery (n = 3) were
      used as the standard of reference. The transplant hepatic artery, celiac trunk,
      superior mesenteric artery, portal vein, superior mesenteric vein, splenic vein,
      hepatic veins, and inferior vena cava (IVC) were evaluated for thrombosis or
      stenosis by two radiologists. RESULTS: Ten vascular complications were identified
      with conventional angiography or surgery: transplant hepatic artery thrombosis (n
      = 3) or stenosis (n = 3), portal vein stenosis (n = 1) or occlusion (n = 2), and
      suprahepatic IVC stenosis (n = 1). All 10 complications were correctly diagnosed
      with MR angiography. There was agreement between results of MR angiography and
      conventional angiography or surgery in 58 of 62 vessels evaluated (94%). There
      was minor disagreement in four vessels (6%). CONCLUSION: Three-dimensional
      gadolinium-enhanced MR angiography may have the potential to enable accurate
      diagnosis of vascular complications of liver transplantation.

PMID- 9530313
TI  - Potential renal transplant donors: evaluation with gadolinium-enhanced MR
      angiography and MR urography.
AB  - PURPOSE: To determine prospectively the feasibility and accuracy of combined
      gadolinium-enhanced magnetic resonance (MR) angiography, MR urography, and MR
      nephrography in the presurgical evaluation of potential renal transplant donors.
      MATERIALS AND METHODS: Twenty-two potential donors for renal transplantation were
      evaluated with 1.5-T MR imaging. MR angiograms were evaluated for the number of
      renal arteries, presence of early arterial branches, and renal artery stenoses.
      The renal collecting system and ureters were evaluated on the MR urograms. Renal
      parenchyma was assessed on the MR nephrogram. Prospective interpretation of MR
      images was compared with that of conventional angiograms and excretory urograms
      and with surgical findings. RESULTS: Gadolinium-enhanced MR angiography enabled
      correct identification of the arterial supply to all 44 native kidneys (44 single
      or dominant renal arteries and nine accessory renal arteries), four of five early
      arterial branches arising in the proximal 2 cm of the renal artery, a mild
      truncal stenosis in one renal artery, and two anomalies of the draining renal
      veins. The MR urogram accurately depicted a duplicated collecting system and mild
      unilateral pelvicalicectasis. The MR nephrogram showed renal size and a solitary
      cyst in one kidney, confirmed with sonography. CONCLUSION: Combined gadolinium
      enhanced MR angiography, MR urography, and MR nephrography can accurately depict
      the arterial supply, collecting system, and renal parenchyma of donor kidneys.

PMID- 9530314
TI  - Transrectal US in male infertility: spectrum of findings and role in patient
      care.
AB  - PURPOSE: To determine the findings at transrectal ultrasound (US) in infertile
      men with low-volume azoospermia and to evaluate its role in patient care.
      MATERIALS AND METHODS: Transrectal US was performed on 276 infertile men with a
      mean age of 34 years (range, 24-52 years) who had documented low ejaculate
      volumes and azoospermia. RESULTS: Of the 276 men, 70 (25.4%) had no anatomic
      abnormalities. In the remaining patients, abnormalities included congenital
      bilateral absence of the vas deferens in 94 (34.1%) patients; bilateral occlusion
      of the vas deferens, seminal vesicles, and ejaculatory ducts by calcification or
      fibrosis in 43 (15.6%) patients; unilateral absence of the vas deferens in 31
      (11.2%) patients; obstructing cysts of the seminal vesicles, vas deferens,
      ejaculatory ducts, or prostate in 26 (9.4%) patients; and ductal obstruction
      secondary to calculi in 12 (4.4%) patients. CONCLUSION: Transrectal US is a safe
      and accurate method for evaluating the distal male reproductive tract that helps
      identify patients with potentially correctable causes of infertility.

PMID- 9530315
TI  - Breast cancer: gadolinium-enhanced MR imaging with a 0.5-T open imager and three
      point Dixon technique.
AB  - PURPOSE: To investigate the three-point Dixon technique as a method for obtaining
      fat-nulled images of contrast material-enhancing breast lesions with a 0.5-T open
      magnetic resonance (MR) imager. MATERIALS AND METHODS: Real and imaginary source
      images were obtained with an interleaved gradient-echo sequence with a repetition
      time of 550 msec and echo times of 12.8, 19.8, and 26.8 msec. Twenty-four to 28
      sections were obtained in the sagittal plane with a 90 degrees flip angle, 256 x
      192 matrix, 3-4.5-mm section thickness, and acquisition time of 10 minutes 54
      seconds. A three-point Dixon reconstruction algorithm was used to generate water
      specific, fat-specific, and combined images from the raw image data. Twelve
      breasts in 10 patients and one healthy volunteer were imaged. RESULTS: Three
      point Dixon images were superior to extended two-point Dixon and fat-suppressed
      images and to images generated by means of subtraction of three-dimensional fast
      spoiled gradient-echo images obtained before contrast material injection from
      those obtained after. CONCLUSION: Three-point Dixon imaging provides a robust
      method for creating fat-nulled images of enhancing breast lesions in the 0.5-T
      open MR environment. Water-specific three-point Dixon images are successful in
      regions of B0 heterogeneity and are superior to fat-suppressed images. They are
      much less susceptible to motion artifact than are subtraction images.

PMID- 9530316
TI  - Occult cancer in women with dense breasts: detection with screening US-
      diagnostic yield and tumor characteristics.
AB  - PURPOSE: To evaluate bilateral screening ultrasound (US) in the detection of
      otherwise occult masses and cancer in women with dense breasts and normal
      mammographic and physical examination findings. MATERIALS AND METHODS: Of 11,220
      consecutive patients prospectively examined, all 3,626 women with dense breasts
      and normal mammographic and physical examination findings underwent physician
      performed screening US. The size and stage of cancers detected with US alone were
      compared with those of cancers detected on mammograms, at physical examination,
      or both, in the remainder of the patients. RESULTS: In the group of 3,626 women,
      11 surgically proved cancers in 11 women (prevalence, 0.30%) were identified with
      US alone. These cancers were not statistically significantly different in mean
      surgical size and stage from those of 61 nonpalpable, mammographically detected
      cancers and were smaller and lower in stage than 64 palpable cancers (P < .01)
      that were diagnosed in the remainder of the population. In the women with dense
      breasts, overall cancer detection increased by 17% (from 63 to 74 tumors), and
      the number of tumors detected only with imaging increased by 37% (from 30 to 41
      tumors). CONCLUSION: Screening US can depict small, early-stage, otherwise occult
      cancers similar in size and stage to mammographically identified nonpalpable
      cancers and smaller and lower in stage than palpable cancers in dense breasts.

PMID- 9530317
TI  - Pulmonary embolus in pregnant patients: survey of ventilation-perfusion imaging
      policies and practices.
AB  - PURPOSE: To assess the policies and practices of nuclear medicine facilities as
      regards ventilation-perfusion (V-P) imaging in pregnant patients suspected of
      having pulmonary embolus. MATERIALS AND METHODS: Surveys were mailed to physician
      directors of 1,000 randomly selected facilities at which nuclear imaging studies
      are performed. Information gathered included use of V-P imaging in pregnant
      patients, written policies, informed consent procedures, and modifications of
      standard protocols. RESULTS: Of the 1,000 surveys mailed, 327 (33%) completed
      surveys were returned. Of these 327 respondents, 220 (67%) reported that they
      perform V-P imaging in pregnant patients suspected of having pulmonary embolus.
      Of these 220 respondents, 115 (52%) routinely obtain informed consent, and 170
      (77%) modify their standard V-P imaging protocol for pregnant patients. The most
      common modification (135 [79%] of 170 respondents) was reduction of the perfusion
      agent dose. Reported practice patterns for written policies, informed consent,
      and modifications did not show statistically significant trends among respondents
      in varying practice settings or geographic locations. CONCLUSION: Most
      respondents perform V-P imaging in pregnant patients suspected of having
      pulmonary embolus, with considerable variability in their policies and practices.

PMID- 9530318
TI  - Frontal lobe shortening in second-trimester fetuses with trisomy 21: usefulness
      as a US marker.
AB  - PURPOSE: To determine whether the frontal lobe is disproportionately smaller than
      normal in second-trimester fetuses with Down syndrome by using prenatal
      ultrasonographic (US) measurements of the frontothalamic distance (FTD).
      MATERIALS AND METHODS: The FTD, measured from the inner table of the frontal bone
      to the posterior margin of the thalamus, was measured in 43 fetuses (mean
      gestational age, 17.2 weeks +/- 1.3 [standard deviation]; range, 15.0-20.4 weeks)
      with chromosomally proved trisomy 21 and in 160 chromosomally normal fetuses
      (mean gestational age, 17.1 weeks +/- 1.5; range, 14.5-22.5 weeks). Other cranial
      biometric ratios also were calculated. RESULTS: The FTD was best predicted from
      the estimated gestational age (EGA) in the euploid population with the quadratic
      equation FTD = -0.0120 x EGA2 + 0.6917 x EGA - 5.2349 (R2 = .731) or from the
      biparietal diameter (BPD) with the linear equation FTD = 0.6837 x BPD + 0.5525
      (R2 = .731). If an observed-to-expected ratio of 0.84 is used as a cutoff sign to
      screen for trisomy 21, a sensitivity of 16%, specificity of 97%, odds ratio of
      6.03 (95% confidence interval, 1.81, 20.1), and relative risk of 5.98 are
      achieved. CONCLUSION: The frontal lobe is statistically significantly smaller in
      fetuses with trisomy 21. US measurement of the FTD may prove to be a useful
      adjunctive screening tool if used with other markers for Down syndrome.

PMID- 9530319
TI  - Acute scrotal symptoms in boys with an indeterminate clinical presentation:
      comparison of color Doppler sonography and scintigraphy.
AB  - PURPOSE: To compare the performance of color Doppler ultrasonography (US) and
      scintigraphy in assessing testicular perfusion in boys with clinically equivocal
      presentations. MATERIALS AND METHODS: Forty-one boys with clinically equivocal
      testicular perfusion underwent color Doppler US and scintigraphy. Studies were
      retrospectively classified as consistent with torsion, consistent with
      nontorsion, or indeterminate. Sensitivity and specificity were determined with
      alternate positivity criteria (indeterminate studies first considered positive
      and then negative for torsion). RESULTS: Color Doppler US demonstrated nine of 11
      cases of torsion and 23 of 30 cases of nontorsion, with one false-positive and
      eight indeterminate studies. Scintigraphy demonstrated 10 of 11 cases of torsion
      and 29 of 30 cases of nontorsion, with two indeterminate studies (both in
      patients with inguinal testis). When indeterminate studies were considered
      positive for torsion, specificity was 77% for color Doppler US versus 97% for
      scintigraphy (P = .05). There were no other statistically significant differences
      between the sensitivities and specificities. CONCLUSION: Color Doppler US and
      scintigraphy demonstrate no statistically significant difference in ability to
      demonstrate testicular torsion in boys with acute scrotal symptoms and
      indeterminate clinical presentations. Owing to its greater specificity,
      scintigraphy may help prevent unnecessary surgery when color Doppler US shows
      equivocal flow.

PMID- 9530320
TI  - Duodenum and duodenal-jejunal junction in children: position and appearance after
      liver transplantation.
AB  - PURPOSE: To correlate upper gastrointestinal study findings of the position of
      the duodenum and duodenal-jejunal junction in children after liver
      transplantation with transplant type, age at transplantation, indication for
      transplantation, and history of surgery or malrotation. MATERIALS AND METHODS:
      Upper gastrointestinal studies in 23 children with a liver transplant were
      reviewed by two pediatric radiologists, and appearance and position of the
      duodenum and duodenal-jejunal junction were recorded. Findings were correlated
      with transplant type, age at transplantation, indication for transplantation, and
      history of surgery or malrotation. RESULTS: The duodenum and duodenal-jejunal
      junction were visualized on anteroposterior spot radiographs in 18 children. In
      10 children, the duodenum and the junction were elevated and to the right of the
      spine; in two, the first and second portions of the duodenum were elevated, but
      the junction was normally located. These 12 children had undergone segmental
      liver transplantation. In the remaining six children, the duodenum and junction
      were normally positioned; three of these children had a whole liver transplant,
      and three had a segmental transplant. CONCLUSION: The duodenum and duodenal
      jejunal junction are often malpositioned in children with a left lobe or left
      lateral segmental liver transplant. Without documented bowel obstruction,
      however, these children should be observed and followed up clinically.

PMID- 9530321
TI  - Subtle pulmonary abnormalities: detection on monitors with varying spatial
      resolutions and maximum luminance levels compared with detection on storage
      phosphor radiographic hard copies.
AB  - PURPOSE: The purpose of this receiver operating characteristic study was to
      compare diagnostic efficacy with images displayed on monitors of varying spatial
      resolutions and maximum luminance levels to that with storage phosphor
      radiographic hard copies. MATERIALS AND METHODS: Seven types of simulated lesions
      were superimposed onto an anthropomorphic chest phantom. Images were viewed by
      five radiologists on a 2,560 x 2,048 pixel monitor (maximum luminance, 75 foot
      lamberts), on two 1,024 x 1,024 monitors with maximum luminance levels of 25 foot
      lamberts and 75 foot-lamberts, respectively, as well as on hard copies. Monitor
      images were viewed both without and with systematic magnification. RESULTS:
      Overall visualization of the lesions was best on hard copies, but visualization
      on the 2,560 x 2,048 monitor was not found to be substantially different. Lines,
      reticular opacifications, and catheters were found to be particularly poorly
      visualized with the 1,024 x 1,024 monitor. These results could be statistically
      significantly improved only with a systematic magnification; however, this
      involved a considerable increase in viewing time. Observer performance was
      markedly inferior with the 1,024 x 1,024 monitor with the lower luminance.
      CONCLUSION: Diagnostic performance with a 1,024 x 1,024 monitor is statistically
      significantly inferior to that with hard copies. A statistically significant
      improvement can be achieved with a high-resolution 2,560 x 2,048 monitor with a
      maximum luminance of 75 foot-lamberts.

PMID- 9530322
TI  - Effect of physical exercise on cartilage volume and thickness in vivo: MR imaging
      study.
AB  - PURPOSE: To quantify, with magnetic resonance (MR) imaging, the in vivo changes
      in cartilage volume and thickness after physical exercise. MATERIALS AND METHODS:
      The patellae of eight volunteers were imaged six times at physical test by using
      a spoiled fat-suppressed gradient-echo sequence with an acquisition time of 4.10
      minutes. The volunteers then performed 50 knee bends, and two more data sets were
      acquired 3-7 minutes and 8-12 minutes after exercise. The patellar cartilage
      volume was determined after three-dimensional reconstruction, and the thickness
      was assessed with a three-dimensional minimal-distance algorithm. RESULTS:
      Whereas repositioning had a small effect on the measurements (mean coefficient of
      variation, 1.4%), a statistically significant decrease in cartilage volume was
      observed 3-7 minutes (mean decrease, 6.0%; P < .05) and 8-12 minutes (mean
      decrease, 5.2%; P < .05) after exercise. The deformation was homogeneous
      throughout the joint surface. In one asymptomatic volunteer, a cartilage lesion
      became more pronounced after exercise. CONCLUSIONS: MR imaging can be used to
      investigate the response of articular cartilage to physical exercise in vivo.
      Patients or volunteers should be allowed a sufficient period of physical rest if
      quantitative measurements of cartilage volume and thickness are to be undertaken
      in longitudinal studies.

PMID- 9530323
TI  - Reporting requirements for skeletal digital radiography: comparison of soft-copy
      and hard-copy presentation.
AB  - PURPOSE: To assess diagnostic performance and reader preference when reporting
      results from digital hard-copy and two soft-copy formats of skeletal digital
      radiography. MATERIALS AND METHODS: The data comprised hand radiographs of
      patients undergoing renal dialysis. Normal hand radiographs obtained in trauma
      patients were assessed as control images. One hundred fifteen images acquired
      with a photostimulable-phosphor computed radiography system were analyzed. Image
      selection and initial assessment were by consensus of two experienced
      radiologists, who graded the radiographic changes of hyperparathyroidism with the
      Ritz scoring system. The images were then presented to four readers in three
      formats: hard-copy output and soft-copy presentations at 2K2 and 1K2 resolutions.
      These readers scored pathologic change and image preference. The results were
      analyzed with the receiver operating characteristic technique. RESULTS: There was
      a significant improvement in diagnostic performance for both soft-copy formats
      relative to the hard-copy format (P < .001). No significant difference in
      diagnostic performance was found between the two soft-copy formats. There was a
      significant preference for both soft-copy formats relative to the hard-copy
      format (P < .01), with the 2K2 soft-copy images preferred to the 1K2 images (P <
      .01). CONCLUSION: Soft-copy reporting can provide superior diagnostic performance
      even for images viewed at a modest (1K2) resolution. The lack of difference
      between the two soft-copy formats has important economic implications with
      respect to departmental hardware requirements.

PMID- 9530325
TI  - The fallen fragment sign.

PMID- 9530324
TI  - Acute brachial neuritis (Parsonage-Turner syndrome): MR imaging appearance-
      report of three cases.
AB  - Magnetic resonance (MR) imaging findings in three patients with acute onset of
      neuritic shoulder pain and weakness included high signal intensity in supra- and
      infraspinatus muscles (n = 2), partial involvement of infraspinatus muscle (n =
      1) and of deltoid muscle (n = 1), and atrophy of supra- and infraspinatus muscles
      (n = 2). Clinical diagnosis of acute brachial neuritis (Parsonage-Turner
      syndrome) correlated with MR imaging results in all cases.

PMID- 9530326
TI  - Bolus-chase MR digital subtraction angiography in the lower extremity.
AB  - A bolus-chase magnetic resonance (MR) angiographic technique performed with a
      prototypic stepping table and coil holder and a 15-20-mL injection of contrast
      material was developed to depict the entire lower extremity. Image acquisition
      was synchronized with passage of the contrast medium bolus through the lower
      extremity. Ten subjects underwent the examination, which was performed in less
      than 1 minute. All major arteries were well demonstrated in all cases.

PMID- 9530327
TI  - Continuous hemodialysis as a treatment option for acute renal failure induced by
      contrast material.

PMID- 9530328
TI  - Endothelin and nephrotoxicity induced by contrast media.

PMID- 9530329
TI  - MR imaging of the internally stabilized spine.

PMID- 9530330
TI  - Do different hormone replacement therapy regimens have different mammographic
      effects?

PMID- 9530331
TI  - Fluorescence in situ hybridization analysis of single-cell trisomies for
      determination of clonality.
AB  - Conflicting data currently exist pertaining to the significance of single-cell
      trisomies found in a 20-cell cytogenetic analysis of hematologic malignancies. In
      order to determine the clonality of the numerical abnormalities found in these
      cases, we performed a retrospective study on a cohort of patients previously
      analyzed by GTG-banding at Rhode Island Hospital, from July 1, 1990 to November
      30, 1996. Fluorescence in situ hybridization (FISH) was performed using
      chromosome enumeration probes on previously fixed bone marrow and, in some cases,
      peripheral blood slides from patients identified to have single-cell trisomies of
      selected chromosomes in 20-cell routine GTG-banded analyses. We seek to determine
      whether the single cell trisomies represent random nonclonal events or "the tip
      of an iceberg." The results of the present study indicate that a single unifying
      answer to the above question does not exist. While some cases are apparently
      random events as predicted by chance, other cases appear to represent "the tip of
      an iceberg." It is therefore important for cancer cytogeneticists to interpret
      the results of each patient on a case-by-case basis and to formulate the most
      optimal strategy for follow-up in the particular case under study.

PMID- 9530332
TI  - Rearrangement of the long arm of chromosome 10 in the prostate adenocarcinoma
      cell line LNCaP.
AB  - Rearrangement of distal 10q is a common feature of many tumor types and tumor
      derived cell lines. More specifically, loss of 10q23-25 has been demonstrated in
      a large proportion of prostate tumors, indicative of the presence of a tumor
      suppressor gene at this location. Using whole-chromosome paints and human genomic
      YAC clones as FISH probes, we have performed a detailed cytogenetic analysis of
      distal 10q rearrangements in the prostate adenocarcinoma cell line LNCaP. Our
      data reveal nonreciprocal translocation of 10q24.1-qter material to two sites on
      chromosome 5q, giving der(5)t(5;10) (q14-23;q24.1)t(5;10)(q35;q24.2) loss of 10q
      material at the 10q24.1 breakpoint. Deleted chromatin at the distal breakpoint
      includes the cytochrome P450IIC (CYP2C) gene cluster, thought to be involved in
      steroid hormone metabolism and therefore of possible significance to the growth
      rate of this androgen-dependent cell line. Deleted material at the proximal
      breakpoint overlaps with a region of deletion at the 10q23-24 boundary recently
      identified in a high proportion of prostate tumors, adding to the evidence for a
      tumor suppressor gene in this interval.

PMID- 9530333
TI  - Lipoblastoma: a case with t(7;8)(q31;q13).
AB  - Lipoblastoma is a rare benign adipose tumor which, in all of the cases so far
      described, presents an involvement of chromosome 8 in the region 8q11-13. We
      hereby report the results of the second case of lipoblastoma studied by
      fluorescence in situ hybridization (FISH), in a 13-month-old boy. An abnormal
      karyotype 46,XY,t(7;8)(q31;q13) was found in 90% of the metaphases examined, in
      agreement with the previously reported observations. We suggest the region 8q11
      13 may contain a relevant locus for lipoblastoma origin.

PMID- 9530334
TI  - A new variant translocation of t(15;17) in a patient with acute promyelocytic
      leukemia (M3): t(15;19;17)(q22;p13;q12).
AB  - The reciprocal translocation (15;17) is specifically associated with acute
      promyelocytic leukemia [APL; M3 subtype according to French-American-British
      (FAB) classification]. A few patients with this disease have complex variant
      translocations. We describe a patient with M3 carrying t(15;19;17)(q22;p13;q12),
      which is a new type of variant translocation. The karyotypic interpretation was
      confirmed by Southern blot analysis with the use of RAR alpha and by fluorescence
      in situ hybridization (FISH) with the use of painting probes of chromosomes 15,
      17, and 19 and a (15;17) translocation DNA probe. The results support the idea
      that the key event in APL is the formation of fusion gene PML/RAR alpha on the
      der(15).

PMID- 9530335
TI  - Genetic alterations in acinic cell carcinoma of the parotid gland determined by
      microsatellite analysis.
AB  - We investigated, for the first time, the genetic alterations at certain
      chromosomal loci in 25 primary parotid acinic cell carcinomas to define the most
      frequently altered chromosomal regions and their association with pathologic
      features and DNA content analysis. Our results showed that 21 (84.0%) of the
      tumors had alteration in at least one of the loci tested. In general, chromosomal
      regions at chromosomes 4p, 5q, 6p, and 17p were more frequently altered than
      those on chromosomes 1p and 1q, 4q, 5p, and 6q. Certain markers at 4p15-16, 6p25
      qter, and 17p11 regions showed the highest incidence of LOH, suggesting the
      presence of tumor suppressor genes associated with the oncogenesis of these
      tumors. LOH was significantly associated only with tumor grade. No apparent
      correlation between LOH and other clinicopathologic and DNA content
      characteristics was identified. Our study broadly defined the chromosomal arms
      and loci that may be targeted for further localization of the minimally deleted
      regions involved in the tumorigenesis of these tumors.

PMID- 9530336
TI  - Clinical relevance of chromosome abnormalities in non-small cell lung cancer.
AB  - The relationship between clonal chromosome alterations and various clinical
      parameters was evaluated in 70 patients with non-small cell lung cancer (NSCLC)
      for whom detailed karyotypic assessment was possible. Included in the analysis
      are karyotypes of 63 previously published cases and seven new NSCLCs. Clinical
      features investigated were diagnosis, tumor stage and grade, gender, smoking
      history measured in pack years, and survival. Certain chromosome abnormalities
      were significantly associated with histologic subtype, tumor grade, stage, and
      prognosis. Rearrangements involving chromosome arms 2p and 3q were more common in
      squamous cell carcinoma (SCC) than in adenocarcinoma (ADC). Loss of 3p was
      observed more often in SCC. Gain of 7p was more frequent in ADC. Rearrangement of
      17p was associated with a lower tumor grade. Rearrangement of Xp and loss of
      chromosome 12 or 22 were each associated with higher tumor stage. Rearrangement
      of 3p or 6q was correlated with a better survival outlook. In contrast, loss of
      chromosomes 4 or 22 portended a poor prognosis. Finally, an increased number of
      marker chromosomes was observed in patients having a higher number of pack years.
      These data indicate that chromosome abnormalities can have clinical and
      pathologic significance in NSCLC.

PMID- 9530337
TI  - Structural analysis of PAX3 genomic rearrangements in alveolar rhabdomyosarcoma.
AB  - In the pediatric cancer alveolar rhabdomyosarcoma, the (2;13)(q35;q14)
      translocation juxtaposes PAX3 and FKHR to produce a chimeric PAX3-FKHR gene. With
      the use of Southern blot methodology, genomic rearrangements of PAX3 intron 7
      were detected in 23 of 23 fusion-positive alveolar rhabdomyosarcomas and were not
      detected in 19 fusion-negative embryonal rhabdomyosarcomas. Rearrangements
      corresponding to the reciprocal FKHR-PAX3 fusion were detected in 21 of 23 PAX3
      FKHR-positive cases, though FKHR-PAX3 transcripts were detected in only 15 of 23
      cases. Mapping experiments demonstrated that breakpoints occurred throughout this
      17.5 kb PAX3 intron and, in 12 of 23 cases, breakpoints clustered within a 4.5-kb
      region at the 3' end of the intron. Chromatin analysis revealed a prominent DNase
      I hypersensitive site at the 5' end of the intron but did not indicate any other
      DNA-protein interactions that might have affected the breakpoint distribution.
      Sequence analysis identified AT-rich regions within the 3' cluster, as well as
      alternating purine-pyrimidine and homopyrimidine elements at the borders of this
      cluster. These finding suggest that translocation breakpoints are constrained to
      PAX3 intron 7 primarily by functional boundaries related to the flanking exons
      and may be secondarily affected by sequence features within this intron.

PMID- 9530338
TI  - Acquired homozygosity (isodisomy) of chromosome 3 in uveal melanoma.
AB  - Cytogenetic investigation of uveal melanoma (UM) has revealed that monosomy 3 is
      the most frequent karyotypic abnormality, present in approximately 60% of cases.
      We investigated a cohort of 41 cases of UM, 19 of which retained two apparently
      normal copies of chromosome 3. Investigation of loss of heterozygosity (LOH)
      status was undertaken in an attempt to detect subcytogenetic loss of genetic
      material in those cases with two copies of chromosome 3. DNA from peripheral
      blood lymphocytes and fresh frozen or paraffin-embedded tumor tissue from 19
      patients was amplified by the polymerase chain reaction for polymorphic loci on
      chromosome 3, including dinucleotide repeats, a tetranucleotide repeat, and
      polymorphic restriction enzyme sites. Three tumors showed LOH at multiple
      informative loci on both short and long arms of chromosome 3. Two additional
      tumors showed localized LOH on 3q, which corresponded to large deletions seen by
      cytogenetic analysis. The remaining 16 tumors showed retention of heterozygosity
      at all informative loci. This study did not detect the presence of cryptic
      deletions but revealed instead complete chromosomal homozygosity or functional
      monosomy, which probably occurred by loss and then duplication of the remaining
      chromosome 3. The demonstration of acquired isodisomy (functional monosomy) in a
      subset of UM increases the percentage of cases with monosomy 3 and provides
      further evidence for a central role of chromosome 3 loss in the molecular
      pathogenesis of uveal melanoma.

PMID- 9530339
TI  - Comparison of chromosomal patterns with clinical features in 165 lipomas: a
      report of the CHAMP study group.
AB  - Soft tissue lipomatous tumors are morphologically heterogeneous. Various
      morphologic features are associated with specific chromosomal patterns and
      clinical features such as age, sex, and tumor site, location, and size. Simple
      lipomas are known to be karyotypically heterogeneous, but this has not been
      correlated with clinicopathological features. In 165 cases of solitary soft
      tissue lipoma, short-term cultures were analyzed cytogenetically. The karyotypes
      were divided into the following groups: normal karyotype; 12q13-15 aberrations;
      6p rearrangements; 13q rearrangements, 8q11-13 aberrations; ring or giant marker
      chromosomes or both; other aberrations. The tumors were reexamined
      morphologically without knowledge of the karyotypic or clinical data. An abnormal
      chromosomal pattern was observed in 129 of 165 cases (78%): in 75 of 90 (83%)
      lipomas in the extremities and in 43 of 63 (68%) trunk wall lipomas. Chromosomal
      aberrations were present in 69 of 90 (77%) subcutaneous tumors and in 59 of 64
      (80%) deep tumors. A normal karyotype was twice as frequent in tumors in patients
      under 30 years of age than in those from older individuals (6 of 16 vs. 30 of
      149, 40% resp. 20%). Apart from the finding that normal karyotypes were more
      common in patients younger than 30 years, there was no significant association
      between cytogenetic pattern and patient sex or age or tumor localization, size,
      or depth. The pathogenetic basis and clinicopathologic relevance (if any) of the
      cytogenetic subtypes among benign lipomas remain unexplained.

PMID- 9530340
TI  - Near tetraploidy in three cases of acute myeloid leukemia associated with
      mediastinal granulocytic sarcoma.
AB  - Granulocytic sarcoma (GS) is a rare manifestation of acute myeloid leukemia
      (AML), blastic transformation of chronic myeloid leukemia, and the
      myelodysplastic syndromes. The mediastinum is an unusual site of presentation. We
      report a series of three female patients with mediastinal GS. They were
      characterized by the presence of large and bizarre blast cells and near
      tetraploidy on cytogenetic analysis. All three patients responded poorly to
      chemotherapy. Near tetraploid AML is a rare entity, usually present in male
      patients, and has not been associated with GS. The clinical and pathological
      similarities in these three cases suggest a distinct category of poor-risk AML
      for which more intensive treatment is needed.

PMID- 9530341
TI  - Near haploidy in breast cancer: a particular pathway of chromosome evolution.
AB  - In a series of 260 cytologically abnormal breast cancers studied in our
      laboratory, we observed a single case of near-haploid karyotype: 27,X,
      +der(1;16)(q10;p10), +7, +14, +15. A review of published cases of near-haploid
      malignancies suggests that near haploidy belongs to a process of chromosome
      evolution distinct from that of most epithelial cancers in which hypodiploidy is
      strongly associated with the occurrence of unbalanced structural rearrangements.
      In near-haploid tumors, chromosome loss is independent from chromosome
      rearrangements and may not be associated with an adverse prognosis.

PMID- 9530342
TI  - Unbalanced chromosomal rearrangements in a metastasizing salivary gland tumor
      with benign histology.
AB  - Benign metastasizing pleomorphic adenoma (BMPA) is a rare tumor of the salivary
      glands. Despite benign histopathologic features, it can metastasize and is
      sometimes lethal. No chromosomal data have been reported for this tumor type. We
      have by chromosome banding and fluorescence in situ hybridization analysis
      examined the short-term cultures of three skeletal metastases from a BMPA and
      identified two related hypodiploid clones: 44,XX,dic(3;22)(p11;q13) or
      der(3)t(3;22)(p11;q?)
      add(22)(q?),der(9;21)(q10;q10),der(13)t(1;13)(q11;p13)/45,XX,-3,der(9;21 )
      (q10;q10),der(13)t(1;13)(q11; p13),?der(22)t(3;22)(q22;q13), +mar. The karyotypic
      features of this BMPA thus differ from the characteristic cytogenetic findings in
      pleomorphic adenomas and carcinomas ex pleomorphic adenoma.

PMID- 9530343
TI  - Reduced DNA repair capacity in breast cancer patients and unaffected individuals
      from breast cancer families.
AB  - It has been suggested that increased fragile site expression in lymphocyte
      cultures can be used as a marker for genetic predisposition to cancer. We wished
      to determine whether aphidicolin (APC), an inhibitor of the DNA repair enzyme DNA
      polymerase alpha, could be used as a reliable biomarker in identification of DNA
      repair capacity in unaffected individuals at high risk from breast cancer
      families. PHA-stimulated lymphocyte cultures, with and without APC, were set up
      in 65 individuals, of whom 14 were breast cancer patients, 26 were unaffected
      individuals from breast cancer families, and 25 were controls. A significant
      proportion of breast cancer patients and unaffected individuals from familial
      breast cancer (FBC) families exhibited premature separation of centromeres (PSC)
      and aneuploidy in the untreated cultures. In the APC treated cultures, almost all
      such individuals exhibited a marked depression of mitotic index and increased
      aneuploidy, as compared to controls. Our results indicate that these individuals
      have defective DNA repair capacity. Such individuals could thus have a much
      higher risk of cancer as compared to persons exhibiting PSC and aneuploidy or DNA
      repair defects alone. We propose that APC may be a valuable biomarker in
      identifying individuals with genetic predisposition to cancer from FBC families.

PMID- 9530344
TI  - Extramedullary presentation of chronic myelogenous leukemia with p190 BCR/ABL
      transcripts.
AB  - We present here a rare case of Philadelphia chromosome (Ph)-positive chronic
      myelogenous leukemia having p190 BCR/ABL with a malignant clinical picture of
      extramedullary blast crisis at onset, followed by rapid evolution to bone-marrow
      blast crisis. The patient was a 44-year-old woman presenting with leukocytosis
      and multiple lymph-node swelling in the neck. Lymph-node biopsy revealed a
      myeloperoxidase-positive blastoma with cell-surface markers of myeloid and T
      lymphoid lineages. Fluorescence in situ hybridization and the reverse
      transcription polymerase chain reaction detected a minor BCR breakpoint but
      failed to detect a major BCR breakpoint. By single-strand conformation
      polymorphism and direct sequencing, no alteration in the TP53 gene was found, and
      no additional chromosomal abnormalities other than Ph were identified. The
      present case suggests that p190 BCR/ABL is associated with the aggressive course
      of the disease.

PMID- 9530345
TI  - Parachordoma: a rare sarcoma with clonal chromosomal changes.
AB  - This is the first report on clonal chromosomal aberrations in a metastatic
      parachordoma lesion. All neoplastic cells had the karyotype 33-47,X,der(X)t(X;3)
      (p11;p11),der(3)t(3;6)(p11;q13), del(6)(q13), -9, -13,r(13), +mar. The presence
      of t(X;3) with a breakpoint at band Xp11 as in synovial sarcoma may suggest a
      common histological origin of the two tumor types.

PMID- 9530346
TI  - Genomic amplification of CCND2 is rare in non-Hodgkin lymphomas.
AB  - Cyclin D2, encoded by CCND2 at 12p13, takes part in the regulation of the cell
      cycle and has been suggested as a candidate for gene amplification in lymphoid
      malignancies. CCND2 is often overexpressed in chronic B-cell disorders, and we
      recently detected genomic amplification of the chromosomal region containing
      CCND2 in two of three investigated non-Hodgkin lymphomas (NHLs) with cytogenetic
      abnormalities involving 12p. In the present study, 58 NHLs without karyotypic
      evidence of 12p aberrations were analyzed by fluorescence in situ hybridization
      with probes for CCND2. No genomic amplification was found, strongly suggesting
      that this abnormality is rare in such NHLs.

PMID- 9530347
TI  - Trisomy 3 as the sole karyotypic change in a pediatric immature teratoma.
AB  - Cytogenetic analysis of short-term cultured cells from an immature ovarian
      teratoma of a 9-year-old girl disclosed an extra copy of chromosome 3 as the sole
      clonal abnormality. The fact that trisomy 3 was previously reported as the only
      karyotypic change in two ovarian germ-cell tumors--one teratoma NOS and one
      immature teratoma--suggests that gain of chromosome 3 constitutes an early and
      pathogenetically important change in a subset of female germ-cell tumors.

PMID- 9530348
TI  - Search for TSG101 germ-line mutations in BRCA1/BRCA2-negative breast/ovarian
      cancer families.

PMID- 9530349
TI  - Direct chromosome analysis of ten primary gastric cancers.

PMID- 9530350
TI  - [Adjuvant for breast cancer chemo-endocrine therapy].
AB  - Early detection and improved therapy together have reduced the mortality for
      breast cancer in the world. A paradox in the management of patients with breast
      cancer is the observation that the majority appear to be curable at the time of
      initial surgery, yet a large number later experience relapse followed by death
      from disease. To combat this problem, systemic drug therapy in conjunction with
      surgery and radiation therapy is now standard for many patient subgroups,
      although the specific decision to use hormonal therapy, combination chemotherapy,
      or both remains complex and controversial. Adjuvant therapy for breast cancer is
      an area in constant evolution. Randomized clinical trials are the critical step
      leading to the identification of improved therapies, that will become our new
      "standards" of management.

PMID- 9530351
TI  - [Progress in diagnosis of gastric cancer and improvement of treatment results].
AB  - The diagnosis of gastric cancer has made remarkable progress in the last 20
      years, thanks to the establishment of diagnostic methodology including double
      contrast radiography, endoscopy (gastrocamera and fiberscope), and endoscopic
      biopsy. The treated number of early gastric cancers began to account for more
      than 50% around 1985 in the majority of Japanese institutions which specialized
      in gastroenterology. It is considered that the improvement of the treatment
      result is mostly due to the increasing number of early gastric cancers, although
      the progress in surgery for advanced cancer may also be a contributing factor.
      Now endoscopic mucosal resection has become a common treatment method for small
      early cancer, and the use of laparoscopic surgery has been increasing. We are now
      in an era seeking for rationalization of treatment options in view of reductive
      and function preserving surgery.

PMID- 9530352
TI  - [Recent advances in endoscopic mucosal resection for early gastric cancer].
AB  - Our indications of endoscopic mucosal resection (EMR) for early gastric cancer
      (EGC) as a radical treatment are as follows: 1) histology: intestinal type; 2)
      macroscopic type: IIa and IIc; 3) without ulcerative change. We do not put
      restrictions on the size of the lesion. EMR is performed on lesions which are
      suspected to have submucosal invasion for a diagnostic purpose. The ratio of EMR
      cases to the total EGC cases is increasing in recent years and amounted to about
      40% of EGCs treated at the National Cancer Center Hospital in '96. From '87-'96,
      we had 440 cases of EGCs (intestinal type, histologically) at the National Cancer
      Center Hospital and National Cancer Center Hospital East. Eighty-five cases
      (19.3%) turned out to have submucosal invasion and judged non-curative resection.
      The overall rate of cut-end-free cases was 72.3%, while the overall rate of
      curative resection (excluding cases with submucosal invasion) was 63.0%. Though
      we had 37 cases of recurrence after EMR, there were no cases of death from the
      original disease with additional treatment or observation (due to complication or
      age). The cut-end-free rates of each period ('87-'90, '91-'93, '94-'96) were
      53.1%, 61.3% and 81.6%, respectively. The mean diameter of the lesion of each
      period became larger, at 11.9 mm, 12.0 mm and 14.0 mm, respectively. To resect a
      larger lesion in one piece, we began EMR with cutting the mucosa around the
      lesion using a newly improved endoscopic device called an insulation-tipped
      diathermic knife (IT knife) from '95. With this IT knife, we could resect 75% of
      the lesions sized 11-20 mm in one piece, while we could resect 29% with the
      conventional method (strip biopsy). Though the results of EMR are improving in
      recent years, new endoscopic technics of EMR to resect easily and surely are
      expected.

PMID- 9530353
TI  - [Laparoscopic surgery for early gastric cancer--its advantages and pitfalls].
AB  - We have successfully established two different laparoscopic procedures for early
      gastric cancer since March 1992, which are laparoscopic wedge resection of the
      stomach using a lesion-lifting method and laparoscopic intragastric mucosal
      resection. The indication is as follows; (A) mucosal cancer, (B) < 25 mm, if the
      lesion is elevated type, (C) < 15 mm and Ul (-), if the lesion is depressive
      type. The advantages of these methods are; 1) minimally invasiveness, 2)
      sufficient surgical margin, 3) feasibility of detailed histology, 4) feasivility
      of perigastric lymph node dissection. In contrast, there are several problems to
      be solved, which are; 1) preoperative diagnostic accuracy of the depth of cancer
      invasion, 2) possibility of reoperation because of sm invasion or lymphatic or
      venous invasion in final histology, 3) possibility of postoperative stenosis
      after laparoscopic intragastric mucosal resection for the lesion near the cardia,
      4) incidence of metachronous multiple gastric cancer. In conclusion, if the
      indication is properly selected, these laparoscopic procedures are curative and
      minimally invasive treatment for early gastric cancer.

PMID- 9530354
TI  - [Assessment of function preserving gastrectomy for early gastric cancer].
AB  - To assess function preserving gastrectomy for early gastric cancer, the
      effectiveness of a reduction of the extent of gastrectomy, preservation of
      pylorus, and preservation of vagus nerve was evaluated. Postoperative physical
      results after pylorus-preserving gastrectomy with preservation of vagus nerve
      (group I, 32 cases), 2/3 distal gastrectomy with preservation of vagus nerve
      (group II, 12 cases), 2/3 distal gastrectomy without preservation of vagus nerve
      (group III, 21 cases) and 4/5 distal gastrectomy without preservation of vagus
      nerve (group IV, 81 cases), were investigated. Postoperative/ preoperative body
      weight ratio in groups I (96.6%) and II (97.4%) was significantly higher than in
      groups III (92.2%) or IV (89.5%). The patients in groups I and II had fewer
      abdominal symptoms than in group IV. The gastric emptying pattern of patients in
      group I was slower than in the other groups. Contraction of the gallbladder in
      groups I and II was better than in group IV. The serum concentration of
      cholecystokinin after meals was low in group I, but increased rapidly in the
      other, groups. Reducing the extent of gastrectomy, preserving the pylorus, and
      preserving the vagus nerve, resulted in preservation of physical status after
      gastrectomy.

PMID- 9530355
TI  - [Extended gastric surgery: is paraaortic lymph node dissection essential for
      advanced gastric cancer?].
AB  - We retrospectively analyzed the clinicopathological findings and prognosis in
      patients who underwent paraaortic lymph node (No. 16) dissection. No. 16
      metastasis was histologically found in 61 of 640 patients (9.5%). Almost all of
      the patients had tumors in the upper third of the stomach or the whole stomach.
      In the patients who had a total of ten or less lymph node metastases after
      curative resection. No. 16 metastases were found at the site of either the left
      or right side of the abdominal aorta. Conversely, No. 16 metastases occurred in
      both left and right sides of the abdominal aorta in patients with 11 or more
      lymph node metastases in total. The five-year survival rate of patients with
      histologically proven No. 16 metastasis was 21%. The indication for No. 16
      lymphadenectomy should be decided by not only the number of No. 16 lymph node
      metastases but also by the total number of removed lymph node metastases. When D4
      lymph node dissection was compared with D2 lymph node dissection in the patients
      without No. 16 involvement on histology, the prognosis of the former was superior
      to the latter in the patients with a tumor in the upper and middle part of the
      stomach. In order to evaluate the efficacy of prophylactic D4 lymphadenectomy,
      randomized clinical trial between D4 and D2 should be performed. It is also
      important that the indication for No. 16 lymph node dissection should be decided
      on the individual patients according to the objective data based on a
      retrospective study.

PMID- 9530356
TI  - [Chemotherapy of gastric cancer].
AB  - At present curative resection is the only radical treatment for gastric cancer,
      although recently developed combination chemotherapy shows increased activity in
      treating locally advanced and metastatic disease. Among several combination
      regimens, those based on biochemical modulation, such as sequential
      methotrexate/5-fluorouracil or low-dose CDDP/5-fluorouracil, are thought to
      provide increased efficacy with decreasing adverse reactions in unresectable
      gastric cancer. Therefore, a prospective randomized clinical trial comparing the
      prognosis of patients receiving adjuvant multi-agent chemotherapy with those
      treated only surgically should be pursued for estimation of the clinical benefit
      of these agents.

PMID- 9530357
TI  - [International perspectives on the treatment of gastric cancer].
AB  - Our experience of treatment of gastric cancer in European and developing
      countries suggested the necessity of the establishment of both operative and
      chemotherapeutic modalities. These modalities should be first based on
      theoretically convincing data and secondarily well analyzed from the viewpoint of
      cost-effectiveness.

PMID- 9530358
TI  - [High-dose biweekly CHOP chemotherapy with granulocyte colony-stimulating factor
      support for patients with aggressive non-Hodgkin lymphoma].
AB  - A pilot study of high-dose biweekly cyclophosphamide, doxorubicin, vincristine
      and prednisolone (CHOP) chemotherapy with granulocyte colony-stimulating factor
      support was carried out at 11 centers. Twenty-five patients with aggressive non
      Hodgkin lymphoma under the age of 65 years old were registered. Lowest values of
      leukocytes and neutrophils scored grade 3 and 4 levels of Eastern Co-operative
      Oncology Group Toxicity Criteria in over 50% of the courses. Very rapid recovery
      of leukocytes and neutrophils was observed, and the duration of leukocytes under
      1,000/microliter was less than 3 days in 72.2% of the courses. Leukocyte counts
      exceeded 2,000/microliter within 3 days in 69.1% of the courses. In most patients
      the hemoglobin and platelet count remained at grade 1 or 2 levels. Fever was seen
      in 15 out of 110 courses. In two-thirds of the 15 courses, fever disappeared
      within 3 days. Thus, administration of the CHOP protocol at biweekly intervals
      was feasible in 76.5% of the courses. Of 22 evaluable patients, there were 11
      complete (CR) and 9 partial (PR) responses with an overall response rate of
      90.9%. Among 13 high risk patients excluding 9 low and low-intermediate groups by
      International Prognostic Index, 7 CRs (53.8%) and 5 PRs (38.5%) were observed.
      This protocol is promising for aggressive chemotherapy of non-Hodgkin lymphoma.

PMID- 9530360
TI  - [Sequential chemotherapy with methotrexate and 5-fluorouracil for advanced
      gastric cancer].
AB  - Sequential chemotherapy with methotrexate and 5-fluorouracil (MTX/5-FU) for
      advanced gastric cancer was given 29 patients. The procedure consisted of weekly
      MTX 100 mg/m2 (i.v.) followed three hours later by 5-FU 600 mg/m2 (i.v.) with
      leucovorin rescue on each of the following two days. Nine of 28 patients (32.1%)
      showed partial response to this treatment. Response rates were 28.6% in the 21
      cases with poorly differentiated adenocarcinoma and 42.9% in the 7 cases with
      well- or moderately-differentiated adenocarcinoma. This procedure was especially
      effective for primary lesions (PR 9/20: 45%) and lymphnode metastases (CR 4 + PR
      4, 8/17: 47.1%). Side effects were mild leukopenia and G-I symptoms such as
      nausea, diarrhea and loss of appetite, except in 1 patient who died of severe
      myelosuppression with sepsis. We concluded that sequential MTX/5-FU therapy is
      fairly effective and the adjuvant chemotherapy of choice for advanced or
      recurrent gastric cancer with not only poorly differentiated adenocarcinoma but
      also well- or moderately-differentiated adenocarcinoma.

PMID- 9530359
TI  - [Phase I study of orally administered UFT plus l-leucovorin].
AB  - A Phase I study of UFT plus l-LV was conducted in 29 patients (pts) with G.I.
      cancer on a multicenter cooperative study. UFT and l-LV were given orally in two
      divided doses for 28 consecutive days, followed by a 14 day-rest period. UFT was
      fixed in three doses, 250, 313 and 375 mg/m2/day, and l-LV was increased in dose
      from 25 to 50 and to 100 mg/body/days. Dose-limiting toxicities were anorexia,
      diarrhea, and nausea/vomiting. The maximum tolerated dose of UFT was 375
      mg/m2/day, and l-LV 25 mg/body/day. Severe myelotoxicity was not observed. There
      were three responders (PR) out of 21 pts with measurable disease at UFT doses of
      313 mg/m2/day and l-LV 50 and 100 mg/body/day. Responses observed were abdominal
      mass (rectal ca), liver metastasis (pancreas ca) and metastasis of liver and
      lymph-node (gastric ca). As a result of pharmacokinetics, plasma concentrations
      of 5-methyl-THF were maintained > 1.0 microM for over 5 hours that was considered
      to have a modulating effect on the plasma concentration. In doses of 50 mg and
      100 mg/body/day of l-LV. No accumulations in plasma were observed in patient
      treated in 28 days by l-LV/UFT therapy. It was suggested UFT and l-LV did not
      interfere with each other's absorption. A Phase II study is recommended, with
      doses of 313 mg/m2/day of UFT and 50 or 100 mg/body/day of l-LV.

PMID- 9530361
TI  - [Concentrations of 5-fluorouracil (5-FU) in serum and tissues at venous injection
      of tegafur or 5-FU--clinical study on colorectal cancer].
AB  - Tissue and serum concentrations of 5-fluorouracil (5-FU) after daily slow venous
      injection of tegafur or 5-FU for 5 days were measured. The serum concentration of
      5-FU elevated to the highest level 6 hours after the venous injection (mean: 30
      ng/ml). Compared with the tegafur injection, the serum concentration of 5-FU
      elevated to a higher peak level 6 hours after the 5-FU injection (mean: 827
      ng/ml). The serum concentration of 5-FU after the tegafur injection tended to be
      maintained longer than after the 5-FU injection. When tegafur was injected, the
      concentration of 5-FU in cancer tissue or lymphnodes was significantly higher
      than in normal tissue. On the other hand, no significant difference was detected
      among the concentrations of 5-FU in the above three tissues when 5-FU was
      injected. Moreover, a significantly higher concentration of 5-FU in lymphnodes
      was caused by the tegafur injection compared to the 5-FU injection.

PMID- 9530363
TI  - [Combination effect of flutamide and leuprorelin acetate on growth of Dunning
      R3327-H prostatic adenocarcinoma in rats].
AB  - Combined androgen blockade using a pure antiandrogen in association with a LHRH
      agonist or surgical castration is the most logical approach. This paper
      demonstrated that flutamide combined with leuprorelin acetate produced a
      significant reduction in the growth rate of Dunning R3327-H prostatic
      adenocarcinoma. Dunning R3327-H prostatic adenocarcinoma, provided by Dr. Norman
      H. Altmann (University of Miami, USA) was subcutaneously inoculated into the
      lateral region of male Copenhagen x Fischer F1 hybrid rat abdomen. The efficacy
      of the tumor growth rate was evaluated by measuring tumor size at 10 weeks after
      the inoculation. Flutamide was orally administered for 10 weeks and leuprorelin
      acetate was subcutaneously administered every 4 weeks. The effective dose of
      flutamide and leuprorelin acetate was determined in preliminary studies, and the
      following doses were used in the study; 15 mg/kg for flutamide, 0.1 mg/kg or 0.4
      mg/kg for leuprorelin acetate. In combination of flutamide with leuprorelin
      acetate at 0.1 mg/kg and 0.4 mg/kg, the tumor inhibition was 94% and 97%,
      respectively. In addition, the weight of accessory sex organs coincided with the
      antitumor effect. Taking the above results into consideration, combined androgen
      blockade using flutamide and leuprorelin acetate may have some beneficial effect
      on prostatic cancer.

PMID- 9530362
TI  - [Phase I study of TAT-59 (a new antiestrogen) in breast cancer. TAT-59 Study
      Group].
AB  - Phase I study of TAT-59 (Miproxifen), an antiestrogen developed in Japan for
      breast cancer, was conducted with the collaboration of 12 hospitals. A single
      dose of 1.25, 5, 10, 20, 40 and 80 mg, or 5 consecutive daily doses of 1.25, 5,
      10, 20 and 40 mg/day, were given orally. After single dosing, no clinical adverse
      effects were found. Decrease of serum Na, Cl, Ca level and increase of serum LDH
      level were observed in one patient after a single dose of 5 mg of TAT. An
      increase in the serum LDH level was also observed in one patient after a single
      dose in the of 10 mg of TAT. An increase in the serum LDH level and total
      bilirubin, increase of eosinophil, K and milky serum were also observed in one
      patient after a single dose of 40 mg of TAT, respectively. All of these abnormal
      values returned to the normal level within 26 days after final administration of
      TAT. No adverse clinical findings nor abnormal laboratory findings were observed
      after consecutive administration of TAT. After postprandial single dosing, the
      time to reach the maximum serum concentration (Tmax) of DP-TAT, dephosphorylated
      metabolite of TAT, and its demethylated metabolite, DMDP, ranged from 5.0 to 7.3
      hr and from 17.0 to 42.8 hr, respectively. The maximum serum concentration (Cmax)
      and AUC of DP and DMDP elevated in a dose-dependent manner. T1/2 of DP and DMDP
      ranged from 24.2 to 41.5, and from 91.9 to 214.7 hr, respectively. There were no
      significant differences between pharmacokinetics of TAT before and after food
      intake. Based on the above results, we concluded that a Phase II study should be
      conducted to evaluate the efficacy, safety and optimal dose of TAT.

PMID- 9530365
TI  - [A CR case of amylase-producing tumor treated by hyperthermochemotherapy].
AB  - A 64-year-old female who was diagnosed with an amylase-producing tumor of unknown
      origin was treated by hyperthermochemotherapy. The patient was admitted with a
      complaint of abdominal fullness due to ascites. Laboratory examination showed
      high levels of serum amylase and tumor markers, including CA15-3, CA 125 and CA
      72-4. Laparotomy showed peritoneal dissemination with histological findings of
      adenocarcinoma of unknown origin. After laparotomy, she was given hyperthermia
      combined with chemotherapy using carboplatin (CBDCA), mitomycin C (MMC) and
      doxifluridine (5'-DFUR). Hyperthermia (13.56 MHz radiofrequency for 40-50 min)
      was performed a total of six times within one and a half months. The total doses
      of CBDCA and MMC were 450 mg and 24 mg, respectively, and 600 mg of 5'-DFUR was
      orally administered every day. By these combined treatments, ascites disappeared
      and serum levels of amylase and all tumor markers were decreased and normalized.
      MRI and echo examination also showed complete disappearance of peritoneal
      metastasis. Two and a half years after the treatment, the patient is alive
      without any evidence of recurrence, which suggests that this combined therapy is
      one of the useful modalities for peritoneal dissemination as well as an
      inoperable tumor itself.

PMID- 9530364
TI  - [Effect of granisetron in preventing emesis due to anti-cancer drug (CDDP)
      administration pulmo-mediastinal malignancies--comparison of simultaneous
      infusion with the conventional method of administration].
AB  - For patients with pulmo-mediastinal malignancies, the antimetic effect of
      granisetron was studied in the following two ways. Firstly in the standard
      method, 40 micrograms/kg of granisetron was infused for 30 minutes, 30 minutes
      before CDDP infusion. Secondly, in the simultaneous method, granisetron was mixed
      with CDDP in a 500 microliters infusion bottle, and then infused over 0.5-3
      hours. Over a 24-hour time course, significantly effective rates (nausea less
      than mild, and vomiting 2 times less) were 72.7% in the simultaneous group (n =
      22) and 52.6% in the standard group (n = 19). The non-effective rates were 18.2%
      and 15.8%, respectively. Although the results were not statistically significant,
      the simultaneous method is easier to perform and it seems to confer a slightly
      better clinical outcome than the conventional method.

PMID- 9530367
TI  - [A case of advanced gastric cancer with virchow's metastasis responding
      remarkably to combination chemotherapy of low-dose CDDP and 5-FU].
AB  - The patient was a 72-year-old female who had Stage IVb advanced gastric cancer
      with Virchow's and paraaortic lymph node metastases. She was considered
      nonresectable and placed on neoadjuvant chemotherapy consisting of low-dose CDDP
      and 5-FU. After 1 course of administration, Virchow's metastasis disappeared, and
      the tumor was remarkably reduced in size. However, this chemotherapy was
      interrupted by toxicity of grade 3 appetite loss, nausea and vomiting, so that
      total gastrectomy and splenectomy were performed, which were non-curative
      operation because of paraaortic lymph node metastases. Histopathological
      examination of the section of the primary tumor revealed that cancer cells had
      almost disappeared, and only a few atypical cells remained in the granulation
      tissue. Eleven months after the surgery, there has been no progression of
      Virchow's and paraaortic lymph node metastases. Combination chemotherapy of low
      dose CDDP and 5-FU appears useful as an inductive approach to advanced gastric
      cancer.

PMID- 9530366
TI  - [A case of advanced gastric cancer successfully treated by UFT and CDDP followed
      by surgical resection proving cancer cell disappearance in the stomach].
AB  - A patient with advanced gastric cancer responded remarkably to UFT combined with
      CDDP. UFT was administered orally for 28 consecutive days at a dose of 400 mg/m2,
      and CDDP was injected intravenously for a day at a dose of 100 mg/m2. Surgical
      resection proved the histological disappearance of cancer cells in stomach.

PMID- 9530369
TI  - [Two patients with obstructive jaundice due to intra-abdominal lymph-node
      metastases of gastric cancer responding to combination chemotherapy with 5-FU and
      CDDP].
AB  - Combination chemotherapy with 5-FU and CDDP was given to two patients with
      obstructive jaundice due to intra-abdominal lymph-node metastases of advanced and
      recurrent gastric cancer. One patient was a primary case associated with lymph
      node metastases of portal fissure and periaorta, and the other was a recurrent
      case associated with lymph-node metastases of hepatoduodenal ligament and
      periaorta. The regimen consisted of 5-FU 1,000 mg/ m2 (day 1-5, continuous
      infusion) and CDDP 100 mg/m2 (day 3, 1 hr drip infusion). The interval was from
      the 6th to 21st day. The response to chemotherapy showed shrinking of intra
      abdominal lymph-nodes and reopening of the biliary tract. The patients could be
      discharged from the hospital without PTBD tube and enjoyed a better quality of
      life (QOL). This therapy is thought to be effective against obstructive jaundice
      due to intra-abdominal lymph-node metastases of advanced and recurrent gastric
      cancer.

PMID- 9530368
TI  - [A case of multiple liver metastasis of gastric cancer responding to hepatic
      arterial infusion chronotherapy].
AB  - A 64-year-old man underwent total gastrectomy and placement of the hepatic
      arterial catheter for advanced gastric cancer with multiple liver metastasis.
      After the operation, repeated hepatic arterial infusion chemotherapy was
      performed. Treatment consisted of a 5-day course of continuous arterial infusion
      of 5-FU. (500 mg/body), leucovorin (21 mg/body) intravenous infusion at 4:00 p.m.
      on days 1-5, mitomycin C (2 mg/body) arterial infusion at 9:00 a.m. on day 5, and
      cisplatin (40 mg/body) arterial infusion at 4:00 p.m. on day 5. A total of 13
      courses of this chemotherapy diminished liver metastasis. During this therapy,
      the patient's condition was good, with no experience of nausea or leukopenia.

PMID- 9530371
TI  - [A case of complete response of metastasis of cervical cancer with a combination
      of CBDCA and 5'-DFUR].
AB  - A 64-year-old woman who had lung metastasis of cervical cancer after radiotherapy
      and hysterectomy was treated with a combination of CBDCA (300 mg/m2/4 w) and 5'
      DFUR (1,200 mg/day x 4 days/week/week). She had complete remission for 10 months
      and showed SCC elevation again. She was treated with the same regimen and
      responded again. Major toxicities were appetite loss and anemia. She received
      more than 20 courses of chemotherapy without admission. Her Performance Status
      was been kept at 0 during the entire treatment. This regimen is thus tolerable,
      allowing an elderly woman to continue with good performance status.

PMID- 9530370
TI  - [The effect of hepatic arterial infusion chemotherapy on the prognosis after
      hepatectomy for hepatocellular carcinoma].
AB  - The effect of hepatic arterial infusion chemotherapy on the prognosis after
      hepatectomy for hepatocellular carcinoma was investigated in patients with risk
      factors for recurrence. The risk factors for recurrence after hepatectomy were
      defined to be metastasis in the liver (+), portal tumor embolus (+), and tumor
      larger than 5 cm in diameter. Out of 87 patients with hepatocellular carcinoma
      who underwent an operation in the past 7 years in our hospital, 60 survived for
      more than 1 year and were enrolled in our study. Thirty-eight of them showed one
      or more risk factors for recurrence, and were considered to be the high-risk
      group. These 38 patients were divided into two groups: one group of 19 treated by
      hepatic arterial infusion chemotherapy using mitoxantrone, and the other group of
      19 given no treatment. The survival rates and non-recurrence rates were compared
      between the two groups. The survival rates after 1 and 3 years for the group
      treated by hepatic arterial infusion chemotherapy were 94.7% and 54.7%,
      respectively. The survival rates for the non-treated group were 53.9% and 32.8%,
      respectively (p = 0.012). The non-recurrence rates after 1 year and 3 years were
      94.7% and 44.2% for the treated group and 52.6% and 23.6% for the non-treated
      group (p = 0.005), respectively. The survival rates and non-recurrence rates
      after 3 years in the treated group were significantly higher (p = 0.012, 0.005),
      respectively. It was concluded, therefore, that post-operation hepatic arterial
      infusion chemotherapy improved the prognosis of the high-recurrence probability
      group.

PMID- 9530372
TI  - [Paclitaxel (taxol): a review of its antitumor activity and toxicity in clinical
      studies].
AB  - Paclitaxel (Taxol) is a new class of anti-tumor agents which act by promoting the
      assembly and inhibiting the disassembly of microtubules. Single-agent studies
      have shown its significant activity for advanced cancers in various organs
      including ovary, lung, breast, and head and neck. Combination therapies with
      other anticancer agents have been extensively investigated in these cancers.
      Paclitaxel combined with cisplatin is now considered to be the standard treatment
      for advanced ovarian cancer. In other cancers, promising results have been
      obtained in several studies of paclitaxel-based chemotherapy. Major toxicities of
      paclitaxel-monotherapy are hypersensitivity reaction, neutropenia, and peripheral
      neuropathy. Combination of other cytotoxic agents sometimes leads to severer
      toxicities such as neurotoxicity with cisplatin and cardiotoxicity with
      anthracycline. Although further evaluation is needed, paclitaxel will be a main
      agent in the treatment of advanced solid tumors.

PMID- 9530373
TI  - [The TNM classification of cancer--from the viewpoint of pathology].
AB  - The 5th international TNM classification (proposed in 1997) is an anatomical
      classification of cancers used all over the world. In Japan, various kinds of
      Japanese classification of cancers have widely been accepted since 1962.
      Researchers may be confounded at international cancer conferences because of some
      differences in these classification. We here summarize the history and criteria
      of the present TNM classification and describe the concept of new N factors
      additional and in the 5th edition. In the Japanese versions of cancer
      classification, the concepts of H and P factors should be reconsidered. The
      importance of the cytologic diagnosis in ascites is discussed and pathological
      grades of differentiation into the new cancer staging are introduced.

PMID- 9530375
TI  - Gadolinium-enhanced 3D MRA of the aortic arch vessels in the detection of
      atherosclerotic cerebrovascular occlusive disease.
AB  - PURPOSE: Our goal was to evaluate non-breath-hold Gd-enhanced 3D MR angiography
      (MRA) for the detection of atherosclerotic occlusive disease of the aortic arch
      vessels and to compare image quality with two breath-hold techniques. METHOD: One
      hundred sixty consecutive patients with known or clinically suspected
      atherosclerotic cerebrovascular occlusive disease underwent Gd-enhanced 3D MRA of
      the aortic arch and great vessels. One hundred twenty-six examinations were
      performed with the body coil after infusion of 40 ml of Gd-DTPA; 89 of these were
      performed without breath-holding and 37 were acquired during suspended
      respiration. Thirty-four examinations were performed in a body phased-array coil
      with breath-holding, a timing examination, and 20 ml of contrast agent by manual
      (n = 17) or power (n = 17) injection. Images were evaluated for the presence of
      blurring and ghosting artifacts and venous enhancement. Of the 27 patients who
      underwent non-breath-hold MRI and digital subtraction angiography (DSA), two
      readers blinded to the DSA results retrospectively evaluated the MRA examinations
      for the presence of occlusive disease of the innominate, carotid, subclavian, and
      vertebral arteries. DSA correlation was not evaluated for the 71 breath-hold
      studies. RESULTS: Sensitivity and specificity for arch vessel occlusive disease
      with non-breath-hold MRA were 38 and 94% for Reader A and 38 and 95% for Reader
      B. Breath-holding significantly reduced blurring and ghosting artifacts (p <
      0.001) when compared with non-breath-hold imaging, and use of 20 ml of contrast
      medium, with a timing examination, resulted in significantly less venous
      enhancement than seen with 40 ml (p < 0.001). CONCLUSION: Non-breath-hold Gd
      enhanced 3D MRA is insensitive for detecting arch vessel occlusive disease.
      Breath-hold imaging, in conjunction with a timing examination and a lower dose of
      contrast agent, improves image quality, but further studies are needed to assess
      diagnostic accuracy.

PMID- 9530376
TI  - 3D breath-hold contrast-enhanced MRA: a preliminary experience in aorta and iliac
      vascular disease.
AB  - PURPOSE: Our goal was to describe a 3D breath-hold (3D BH) contrast-enhanced MRA
      technique and apply the technique to patients with known or suspected aortic and
      iliac artery disease. METHOD: A fat-suppressed 3D GRE pulse sequence was designed
      with a total of 16 partition encodings. This took < 24 s for data acquisition in
      the abdomen and pelvis and was easily achieved during a single breath-hold. The
      technique was applied to 26 patients who presented with either known or suspected
      abdominal aortic or iliac vascular diseases. For comparison, in 19 patients a 2D
      TOF MRA pulse sequence with a traveling saturation band was used. Angiographic
      correlation was made in 18 studies. RESULTS: The 3D BH MRA was easily applicable
      in the evaluation of vascular anatomy and pathology. In three cases, it was
      superior to 2D TOF and conventional angiography for visualizing clot within the
      wall of an aneurysm in the abdominal aorta. In 20 cases, both MRA techniques
      overestimated the degree of stenosis in the lower peripheral vessels; however,
      this was more pronounced on 2D TOF. In five cases, the aneurysm wall was clearly
      defined by 3D BH MRA, whereas there was considerable signal loss in 2D TOF due to
      complex flow. With 3D BH MRA, the entire vessel territory both in abdominal aorta
      and in iliac vessels was visualized in all cases without signal falloff in the
      FOV. Breath-holding provided static images of the vessels that were free of
      blurring due to respiratory motion. CONCLUSION: Preliminary experience suggests
      that 3D BH with its distinct advantage of speed may serve as a useful screening
      tool for patients who cannot have conventional angiography or tolerate a lengthy
      MR examination of the abdominal aorta and iliac arteries.

PMID- 9530377
TI  - Helical CT angiography of living renal donors: comparison with 3D Fourier
      transformation phase contrast MRA.
AB  - PURPOSE: The purpose of this study was to determine whether helical CT
      angiography (CTA) or MR angiography (MRA) is the optimal method to use as a
      preoperative examination for anatomic arterial assessment of living renal donors.
      METHOD: Eighteen candidates to be renal donors underwent helical CTA, 3D Fourier
      transformation phase contrast (3D-FT-PC) MRA, and digital subtraction angiography
      (DSA). The CTA and MRA were interpreted separately by three readers
      independently, and these results were correlated with the findings of DSA.
      RESULTS: DSA showed nine accessory renal arteries and 10 prehilar branches. CTA
      revealed seven or eight accessory renal arteries. MRA showed six or seven
      accessory arteries. Of 10 prehilar branches, 7-9 branches were detected with CTA
      and 5-8 branches with MRA. CONCLUSION: Helical CTA is superior to 3D-FT-PC MRA
      for evaluating the arterial anatomy of living renal donors.

PMID- 9530378
TI  - Measurement of aortic and pulmonary flow with MRI at rest and during physical
      exercise.
AB  - PURPOSE: Our aim was to assess the feasibility of measuring great vessel flow
      during submaximal exercise using MR flow mapping. METHOD: In 16 healthy
      volunteers, MR measurements of great vessel flow were obtained at rest and during
      two levels of submaximal physical exercise using an MR-compatible bicycle
      ergometer. RESULTS: Great vessel flow showed good correlation at rest and during
      exercise (r = 0.9, p < 0.0005). Significant increase in heart rate was observed
      during exercise. Aortic flow volume increased from 64 +/- 13 ml/beat at rest to
      71 +/- 11 ml/beat at 50 W (p < 0.0005) to 79 +/- 13 ml/beat at 100 W (p <
      0.0005). Pulmonary flow volume increased from 63 +/- 14 ml/beat at rest to 70 +/-
      13 ml/beat at 50 W (p < 0.005) to 76 +/- 12 ml/beat at 100 W (p = NS).
      CONCLUSION: Quantification of great vessel flow can be performed safely in
      healthy volunteers using MR flow measurements during submaximal physical
      exercise. These measurements may be used to study hemodynamic abnormalities in
      patients with cardiac disease.

PMID- 9530379
TI  - MR angiography of aneurysms in Behcet disease: a report of four cases.
AB  - PURPOSE: The purpose of this study was to evaluate the use of MR angiography
      (MRA) in Behcet disease patients with arterial aneurysms. Avoidance of
      angiography is desirable in patients with Behcet disease because arterial
      angiography carries the risk of pseudoaneurysm formation at the puncture site and
      intravenous digital subtraction angiography is frequently complicated by puncture
      site thrombophlebitis in this patient group. METHOD: Four men with Behcet disease
      and aneurysms were evaluated with MRA. The patients ranged between 30 and 48
      years of age. All subjects had known Behcet disease for > 10 years. Multiplanar
      T1-weighted images were followed by 2D breath-hold MRA without gadolinium
      administration for chest studies and 2D-TOF MRA for the extremities. RESULTS: One
      aortic arch, one descending aorta, one pulmonary artery, one common femoral
      artery, and one popliteal artery aneurysm were depicted in four subjects with
      MRA. Surgery was successfully performed in three subjects without the need for
      further angiographic workup. One subject with two aneurysms in the thoracic aorta
      is currently under steroid treatment. CONCLUSION: MRA combined with T1-weighted
      SE images adequately demonstrated the aneurysms in four patients and made it
      possible to avoid contrast angiography.

PMID- 9530380
TI  - Correlations between vascular calcification and atherosclerosis: a comparative
      electron beam CT study of the coronary and carotid arteries.
AB  - PURPOSE: Electron beam CT (EBCT)-derived coronary artery calcium scores correlate
      with the extent of atherosclerosis, but there is a substantial variance about the
      general relationship between coronary calcification and coronary atherosclerosis.
      The relationship between calcification and atherosclerosis may also differ in
      various arteries. This study was designed to evaluate whether the relation
      between carotid artery intima-media thickness (IMT) and carotid artery calcium
      could be used as a correction factor to improve the correlation between coronary
      calcification and coronary atherosclerosis. METHOD: We measured atherosclerosis
      in the coronary and carotid arteries by angiography and ultrasonography,
      respectively, and quantified coronary and carotid calcium deposition with EBCT in
      50 subjects. The correlation between the findings in the carotid and coronary
      arteries was investigated. RESULTS: Coronary artery calcium score correlated with
      coronary angiography and with carotid calcium score. Coronary stenosis correlated
      with carotid IMT. There was no meaningful correlation of carotid IMT and carotid
      calcium. CONCLUSION: There is an intraindividual variation in the relationship of
      plaque mass to calcification among different vessels. The relation between
      carotid artery calcification and carotid IMT is not predictive of the relation
      between coronary artery calcification and coronary obstruction.

PMID- 9530381
TI  - Virtual angioscopy using spiral CT and real-time interactive volume-rendering
      techniques.
AB  - Our purpose was to describe a technique for visualizing the inner contours of the
      vasculature using contrast enhanced spiral CT and volume rendering techniques.
      Because the technique is similar to using a camera to look inside vessels, we
      call this technique "virtual angioscopy." Preliminary results suggest virtual
      angioscopy using volumetric 3D rendering techniques as a potentially useful
      technique for the noninvasive evaluation of vascular pathology.

PMID- 9530382
TI  - Ground-glass attenuation in nodular bronchioloalveolar carcinoma: CT patterns and
      prognostic value.
AB  - PURPOSE: The purpose of our study was to assess the CT patterns and prognostic
      value of ground-glass attenuation in nodular bronchioloalveolar carcinoma (BAC).
      METHOD: We retrospectively reviewed CT examinations of 22 patients with 24
      nodular BACs who underwent surgery. CT and pathologic findings were analyzed and
      correlated with postoperative course of disease. RESULTS: We detected five
      patterns of ground-glass attenuation associated with nodular BAC: pure ground
      glass nodule (n = 1), ground-glass nodule with superimposed lymphangitis (n = 1),
      nodule with mixed areas of ground-glass attenuation and consolidation (n = 2),
      ground-glass halo around nodule (halo sign) (n = 3), and nodule associated with a
      plurisegmental area of ground-glass attenuation (n = 1). Two patients with the
      halo sign and a third patient with a plurisegmental area of ground-glass
      attenuation rapidly developed diffuse pulmonary disease by bronchogenic spread
      and died a few months after surgery. CONCLUSION: Our series demonstrates that
      focal BAC may progress to diffuse pulmonary involvement by bronchogenic spread.
      The presence of a large area of ground-glass attenuation associated with a
      nodular BAC might be the CT sign of an aggressive biologic behavior. In these
      cases there is a high likelihood for diffuse disease to develop from bronchogenic
      spread.

PMID- 9530383
TI  - High resolution CT findings of miliary tuberculosis.
AB  - PURPOSE: The purpose of this study was to analyze high resolution CT (HRCT)
      findings of miliary tuberculosis and to assess the clinical utility of HRCT in
      the management of patients with miliary tuberculosis. METHOD: We reviewed
      retrospectively HRCT scans of 25 patients with histopathologically (n = 16)
      and/or microbiologically (n = 9) proven miliary tuberculosis. RESULTS: HRCT scans
      showed miliary nodules in 24 patients, which varied in size from 1 to 5 mm, with
      either sharply (n = 21) or poorly (n = 3) defined margins. The nodules had
      diffuse random distribution throughout both lungs and within the secondary
      pulmonary lobules. In 23 patients, areas of ground-glass opacities (GGOs) were
      observed with variable extent and distribution. The patients who had dyspnea
      showed large areas of GGOs, and two patients with impending adult respiratory
      distress syndrome revealed extensive GGOs. Both intralobular reticulation and
      interlobular septal thickening were seen in 10 patients. CONCLUSION: Miliary
      nodules and GGOs are the predominant HRCT findings in patients with miliary
      tuberculosis, and HRCT scans are helpful in the early diagnosis and proper
      management of patients with miliary tuberculosis.

PMID- 9530384
TI  - Mycobacterium xenopi pulmonary infection: evaluation with CT.
AB  - PURPOSE: Our goal was to describe the CT appearances of Mycobacterium xenopi
      pulmonary infection. METHOD: A retrospective study period of 75 months was used.
      Eight immunocompetent patients fulfilled the American Thoracic Society criteria
      for M. xenopi infection and had CT scans of the thorax. CT scans were reviewed by
      two observers, and decisions were reached by consensus. RESULTS: Seven patients
      demonstrated upper lobe cavitary disease: one mass with cavity, one nodule with
      cavity, three consolidation with multiple cavities, and two cavities only. One
      patient demonstrated upper lobe consolidation only. All patients demonstrated
      adjacent lung architectural distortion indicating fibrosis and centrilobular
      nodules suggesting endobronchial spread of infection. Seven patients had a
      clinical history of preexisting chronic obstructive pulmonary disease that was
      confirmed by CT. Four patients demonstrated adjacent pleural disease. CONCLUSION:
      M. xenopi pulmonary infection usually affects patients with preexisting pulmonary
      emphysema. It predominantly affects the upper lobes, usually with cavitary
      opacities and evidence of fibrosis and endobronchial spread of infection.

PMID- 9530385
TI  - Sarcoidosis activity: correlation of HRCT findings with those of 67Ga scanning,
      bronchoalveolar lavage, and serum angiotensin-converting enzyme assay.
AB  - PURPOSE: The objective of this study was to correlate the findings of sarcoidosis
      on high resolution CT (HRCT) with indexes of disease activity as measured with
      67Ga scan, bronchoalveolar lavage (BAL), and serum angiotensin-converting enzyme
      (SACE) assay. METHOD: Twenty-nine patients with proven sarcoidosis underwent HRCT
      scan, 67Ga scan, BAL, and SACE assay within a 1 month period. The extent of
      parenchymal involvement by nodules, consolidation, ground-glass attenuation, and
      linear opacities was quantified to the nearest 10% of surface area affected on
      the CT examination. Whole-lung gallium uptake was quantified and the percentage
      of BAL-recovered lymphocytes (BAL-%LC) and SACE levels obtained by chart review.
      CT scores of disease extent were correlated with measured indexes of activity
      using the Spearman rank correlation coefficient. RESULTS: The mean extent of
      nodules, consolidation, ground-glass attenuation, and linear opacities on HRCT
      images was 15.1 +/- 16.6, 1.6 +/- 4.0, 17.5 +/- 25.4, and 7.6 +/- 9.6%,
      respectively. The extent of nodules and consolidation correlated with the
      intensity of lung gallium uptake (r = 0.46, p < 0.02), BAL-%LC (r = 0.50, p <
      0.01), and SACE levels (r = 0.38, p < 0.05). No significant correlation was found
      between extent of ground-glass attenuation or linear opacities with any indexes
      of disease activity. CONCLUSION: On HRCT scan, nodules and consolidation in
      sarcoidosis reflect disease activity as measured by 67Ga scan, BAL, and SACE
      assay.

PMID- 9530386
TI  - The detection of pulmonary metastases by helical CT: a clinicopathologic study in
      dogs.
AB  - PURPOSE: We sought to determine the accuracy of helical CT in the detection of
      pulmonary metastases. METHOD: Four anesthetized dogs with metastatic osteosarcoma
      underwent helical CT with a collimation of 5 mm, a pitch of 2, and a
      reconstruction interval of 5 mm. All macroscopically evident metastases were
      recorded at autopsy. CT images were independently reviewed by 10 radiologists and
      compared with pathologic results. Alternate slices in the dog with the most
      metastases were microscopically examined in their entirety. RESULTS: Pathologic
      examination of the lungs revealed 132 macroscopically evident pulmonary
      metastases, of which 74 (56%) were detected by at least one reader. Forty-four of
      the 99 (44%) metastases of < or = 5 mm in diameter were detected by at least one
      reader compared with 30 of 33 (91%) metastases of > 5 mm in diameter (p <
      0.0001). The 10 readers reported a total of 107 false positives. Complete
      microscopy of alternate slices in the dog with the most metastases (n = 68)
      revealed an additional 38 micrometastases of < or = 3 mm in diameter. None of the
      32 micrometastases of < or = 1 mm were detected by CT. CONCLUSION: Helical CT has
      some limitations in the detection of pulmonary metastases.

PMID- 9530388
TI  - Pulmonary alveolar microlithiasis: high-resolution CT and MR findings.
AB  - We report the high-resolution CT (HRCT) and MR findings in a case of pulmonary
      alveolar microlithiasis. HRCT revealed that the black pleural line on a chest
      radiograph was caused not by subpleural cysts but by a fat-dense layer between
      ribs and the calcified parenchyma. MRI showed both lower zones with diffusely
      increased signal intensity on T1-weighted images. We speculated it was caused by
      the accumulation of small-sized calcific particles.

PMID- 9530387
TI  - Thoracic imaging features of patients with antiphospholipid antibodies.
AB  - PURPOSE: Our aim was to determine the thoracic manifestations of patients with
      antiphospholipid antibodies (APAs). METHOD: We performed a retrospective review
      of the clinical records and thoracic imaging studies of 88 patients (63 women, 25
      men; mean age 47 years) with APAs to determine the spectrum of thoracic disease.
      RESULTS: Nine patients (10%) had thoracic abnormalities, including eight with
      pulmonary embolism (PE) and one with aortic thrombus. One patient with PE had
      subclavian vein thrombosis. Coexistent thromboses included deep venous thrombosis
      of the leg in six patients. CONCLUSION: PE was the most common thoracic
      abnormality in our patients. The presence of these antibodies should be suspected
      in patients with PE of otherwise unexplained etiology.

PMID- 9530389
TI  - Hermansky-Pudlak syndrome with diffuse pulmonary fibrosis: radiologic-pathologic
      correlation.

PMID- 9530390
TI  - MRI of the abnormal pediatric hand and wrist with plain film correlation.
AB  - Based on a pool of 24 selected cases of nontraumatic pathology of the hand and
      wrist in patients under the age of 18 years, collected from three pediatric
      hospitals, the authors have illustrated a number of congenital, inflammatory, and
      infectious conditions as well as tumors of bones and soft tissues, utilizing MRI
      with plain film correlation. Due to different MR signal characteristics, the
      etiology of macrodactyly may be recognized, e.g., vascular and/or fatty versus
      neurofibromatosis, etc. In septic arthritis, MR has shown abnormal marrow signal
      in adjacent bones denoting osteomyelitis, often unexpected from the plain film
      appearance. Tenosynovitis has a specific MR appearance: Fluid in the tendon
      sheath gives high signal on T2-weighted imaging. In arthritis--because of the
      associated hyperemia--there is definite synovial enhancement easily visible
      immediately after Gd-chelate injection. Gd also helps identify viable tissues
      postinfection as well as viable tumor tissue (versus scar or necrotic tissue) in
      tumors. Plain radiography is the imaging method of choice for diagnosis and
      differential diagnosis of most cases of bone cysts, tumors, and tumor-like
      conditions, e.g., simple and aneurysmal bone cysts, enchondroma, and osteoid
      osteoma. In the study of masses, MRI gives excellent detail regarding tumor
      staging and the extent of soft tissue tumors as well as the soft tissue component
      of bone tumors. In the hand and wrist, aneurysmal bone cysts are usually confined
      within a metacarpal or carpal bone, showing high signal intensity on T2-weighted
      imaging, often with fluid/fluid levels. If ganglion cysts are excluded, the most
      commonly encountered soft tissue masses are the vascular malformations. MR
      angiography can demonstrate the vascularity of the lesion. Some benign soft
      tissue lesions have a characteristic MR appearance, e.g., ganglion cysts,
      lipomata, and accessory muscles.

PMID- 9530391
TI  - Peroneus brevis tendon in normal subjects: MR morphology and its relationship to
      longitudinal tears.
AB  - PURPOSE: The most prevalent, yet unproven, theory for the development of
      longitudinal splits of the peroneus brevis tendon is the compression of the
      peroneus brevis tendon by the peroneus longus tendon in dorsiflexion. The goal of
      our study was to provide insight into this pathomechanism by evaluating the shape
      of the peroneus brevis tendon and its relationship to the adjacent structures in
      the fibular groove during plantarflexion and dorsiflexion. METHOD: The MR images
      of 13 ankles in asymptomatic adult volunteers were performed in full dorsiflexion
      and plantarflexion. The axial MR images were assessed for the shape of the
      peroneus brevis tendon and its relationship to the peroneus longus tendon and
      posterior cortex of the fibula in both plantarflexion and dorsiflexion. RESULTS:
      In 12 of the 13 volunteers, the peroneus brevis tendon was located anterior or
      anteromedial to the peroneus longus tendon in the fibular groove. In those
      volunteers the peroneus brevis tendon was more flattened and compressed against
      the fibular groove by the overlying peroneus longus tendon in dorsiflexion than
      plantarflexion. Fat planes were noted in plantarflexion between the peroneal
      tendons as well as between the peroneus brevis tendon and the fibular groove.
      These were obliterated in dorsiflexion. CONCLUSION: The changes in configuration
      of the tendon of the peroneus brevis tendon in dorsiflexion compared with
      plantarflexion provide support to our present understanding of the pathomechanism
      of longitudinal tears of the peroneus brevis tendon.

PMID- 9530392
TI  - Longitudinal tibial stress fractures: a report of eight cases and review of the
      literature.
AB  - PURPOSE: We present the imaging features of longitudinal stress fractures in
      eight patients and evaluate the literature to determine which tests are most
      useful for making this diagnosis. METHOD: Three musculoskeletal radiologists
      retrospectively reviewed eight cases of longitudinal tibial stress fractures
      presenting between 1988 and 1994. Reports on 36 cases, cited in the literature
      between 1960 and 1996, also were reviewed. Imaging modalities used and
      characteristic imaging features were noted. RESULTS: Plain radiographs had a
      characteristic appearance in approximately 28% of patients. Initially, plain
      films were negative, and in most cases, they eventually showed characteristic
      radiographic features. However, 25% of cases failed to demonstrate a plain film
      abnormality, with the diagnosis made by other modalities. CT or MRI is often
      diagnostic, and longitudinal stress fractures have characteristic imaging
      features with each modality. While sensitive, bone scan has lower specificity
      than either CT or MRI. CONCLUSION: Longitudinal stress fractures have
      characteristic imaging features, and familiarity with these features is necessary
      for timely and efficient diagnosis, avoiding morbidity due to delay or use of
      unnecessary tests.

PMID- 9530393
TI  - MR evaluation of human anterior cruciate ligament autograft on oblique axial
      imaging.
AB  - PURPOSE: The purpose was to observe the changing MR appearance of stable anterior
      cruciate ligament (ACL) grafts on oblique axial images. METHOD: Fifty-five knees
      in 44 patients were studied with MRI 1-54 months after arthroscopic ACL
      reconstruction with double-looped autogenous semitendinosus and gracilis tendons.
      Knees with poor stability were excluded from this study. Examinations were
      performed at 0.2 T with SE proton density and T2-weighted sagittal and oblique
      axial images. RESULTS: High signal intensity areas covered the grafts 1-3 months
      after surgery. The high signal subsequently extended into the intertendinous
      bundles. The entire graft gradually became a low signal intensity bundle again
      after 12 months. Grafts were classified by their appearance on the oblique axial
      images. CONCLUSION: We conclude that high signal intensity can be seen within
      stable ACL grafts.

PMID- 9530394
TI  - CT-guided bone biopsy in a cancer center: experience with a new apple corer
      shaped device.
AB  - In this article we report our experience with CT-guided bone biopsy (CTGBB) using
      a new nondisposable bone biopsy device with in a uniform protocol for all lesions
      and compare our results with data from bone biopsies obtained with other
      techniques. With this biopsy device, the specimen is collected in a 20 x 2 mm
      chamber of an apple corer-shaped needle. In 46 consecutive cancer patients that
      were candidates for bone biopsy, 50 CTGBB procedures were performed and analyzed.
      Lesions with cortical defects and/or surrounding soft tissue infiltration were
      excluded. There were no complications. Of 50 CTGBB procedures, 90% were
      diagnostic. Four of the five inconclusive biopsies were repeated: All were
      conclusive, one malignant. Of 19 with CT-indistinguishable lesions (detected on
      MRI or isotope studies), 35% were malignant. Thirty-eight percent of the lesions
      were not accompanied by pain. The procedure was less painful than injection of
      the local anesthetic prior to biopsy in 90% of the cases. With the new device,
      CTGBB procedures can be carried out safely. Biopsy with the described technique
      has a high diagnostic output, better results than those of biopsy with reported
      uniform techniques, and equal results to the best results of combined techniques.
      If a lesion is not distinguishable on CT and/or not accompanied by pain,
      malignancy is not ruled out. CTGBB in the described technique is less or equally
      time consuming, less painful, and cheaper than reported for other bone biopsy
      procedures.

PMID- 9530395
TI  - Dual-phase helical CT of locally invasive pancreatic adenocarcinoma.
AB  - Dual-phase helical CT permits imaging of the pancreas and the peripancreatic
      structures in the arterial dominant and portal venous phases of enhancement,
      providing information crucial in the assessment of the local extent of pancreatic
      adenocarcinoma. This essay reviews the dual-phase helical CT findings of local
      extension that preclude potentially curative surgery, including vascular
      involvement, ligamentous or mesenteric invasion, extension of the tumor to
      involve the stomach or duodenum, and invasion of adjacent solid organs.

PMID- 9530396
TI  - Gastric cancer: evaluation of triphasic spiral CT and radiologic-pathologic
      correlation.
AB  - PURPOSE: The purpose of this study was to evaluate the utility of triphasic
      spiral CT with water-filling method in the preoperative T staging of gastric
      cancer. METHOD: We performed triphasic spiral CT in 108 patients with gastric
      cancer (53 with early and 55 with advanced gastric cancer). The CT findings were
      prospectively analyzed and correlated with the histopathologic findings. Spiral
      CT scans were assessed for the layered pattern of the normal gastric wall, the
      detectability of tumor, the enhancing pattern of the tumor, and the depth of
      tumor invasion. RESULTS: The layered pattern of the normal gastric wall was
      clearly demonstrated in the arterial-dominant or parenchymal phase. All 12 early
      cancers detected with spiral CT were most clearly depicted in the arterial
      dominant or parenchymal phase. On the other hand, 15 (28%) of 54 advanced cancers
      were most clearly depicted in the equilibrium phase due to the gradual
      enhancement from the inner mucosal side of the tumor. Most of these tumors were
      scirrhous type tumor containing abundant fibrous tissue stroma. The accuracy of
      spiral CT for tumor detection and T staging was 98 and 82%, respectively, in
      advanced gastric cancer and 23 and 15%, respectively, in early gastric cancer.
      CONCLUSION: Spiral CT with triphasic scan technique improved the accuracy of
      estimating the depth of tumor invasion in advanced gastric cancer.

PMID- 9530398
TI  - Helical CT and 3D reconstruction of ureteropelvic junction obstruction: accuracy
      in detection of crossing vessels.
AB  - PURPOSE: The purpose of our study was to evaluate the accuracy of 3D helical CT
      and its value in surgical planning for the treatment of ureteropelvic junction
      obstruction (UPJO). METHOD: CT scans and 3D reconstruction of renal vessels and
      the renal pelvis were performed in 20 cases of UPJO treated by open surgery. We
      analyzed scans in search of a vessel at the junction and its position relative to
      the UPJ. Helical CT scans and 3D reconstructions were correlated with macroscopic
      surgical findings. RESULTS: CT scans demonstrated the presence of a UPJO in all
      cases. Crossing vessels were present at the junction in 13 of 20 cases. The
      vessel crossed the junction posteriorly in six cases and anteriorly in seven
      cases. Macroscopic surgical findings were in agreement with helical CT
      reconstructions in 100% of the cases. CONCLUSION: Axial scans together with 3D
      reconstruction are an accurate way of detecting crossing vessels when UPJO
      occurs, and the choice of the most adequate surgical technique is facilitated.

PMID- 9530397
TI  - CT appearance of sclerosing peritonitis in patients on chronic ambulatory
      peritoneal dialysis.
AB  - PURPOSE: The purpose of this study was to describe the CT appearances of
      sclerosing peritonitis (SP) in patients on chronic ambulatory peritoneal dialysis
      (CAPD) and to compare these findings with the CT appearances in a control group
      of CAPD patients who did not develop SP. METHOD: The CT findings in 10 patients
      with SP were compared with those from a "control group" of 71 patients without SP
      who were on long-term CAPD and had also undergone at least one CT examination.
      Particular reference on CT examination was made to the appearance of the
      peritoneum and small bowel and the presence or absence of loculated fluid
      collections. RESULTS: Peritoneal abnormalities (calcification/thickening) were
      noted in 100%, loculated fluid collections in 90%, and small bowel abnormalities
      (tethering/dilatation) in 60% of the patients with SP. In the control group of
      patients, peritoneal abnormalities were noted in only 7%, loculated fluid
      collections in 15%, and small bowel dilatation in 5.7%. CONCLUSION: Peritoneal
      thickening, peritoneal calcification, loculated fluid collections, and tethering
      of the small bowel appear to be diagnostic of SP. In a small group of patients
      with follow-up CT scans, new, or progression of, CT findings correlated with the
      clinical severity of SP.

PMID- 9530399
TI  - Retropsoas positioned bowel: incidence and clinical relevance.
AB  - PURPOSE: Our goal was to assess the incidence of retropsoas positioned large or
      small bowel in the population and to examine factors predisposing to its
      formation. METHOD: The presence of retropsoas positioned bowel was
      retrospectively studied in 1,852 abdominal CT examinations of 1,055 men and 797
      women, 648 younger and 1,204 older than 50 years. All examinations were
      considered normal or demonstrated findings that were unrelated to the position of
      the bowel. RESULTS: Retropsoas positioned colon (RPC) was observed in 51 (2.8%)
      cases for the ascending and 45 (2.3%) for the descending colon. RPC appeared more
      frequently in younger (< 50 years) than older patients and in individuals with
      decreased amount of retroperitoneal fat. Retropsoas position of small bowel loops
      was observed in 11 (0.6%) patients, all exhibiting paucity of retroperitoneal
      fat. CONCLUSION: Because of its prevalence, retropsoas positioned bowel should be
      considered when performing percutaneous diskectomy or other interventional
      procedures in the posterior retroperitoneum.

PMID- 9530400
TI  - Artificial paravertebral widening for percutaneous CT-guided adrenal biopsy.
AB  - A percutaneous adrenal biopsy under CT guidance is described. The biopsy was
      performed after injection of physiologic saline solution into the paravertebral
      space, creating a wider pathway for needle insertion. This technique has been
      previously reported for biopsy of thoracic lesions, but in our case it was used
      for biopsy of a relatively inaccessible adrenal lesion. This artificial window
      that is formed by displacing the pleura laterally allows a direct and potentially
      safer access route to the retroperitoneum, avoiding puncture of pleura,
      diaphragm, and abdominal structures.

PMID- 9530401
TI  - Lymphoepithelial cysts of the pancreas: demonstration of lipid component using CT
      and MRI.
AB  - We present two cases of surgically proven lymphoepithelial cyst (LEC) of the
      pancreas that had a lipid component visualized by CT and MRI. Identification of
      this component in a pancreatic cystic lesion is a key to favor the diagnosis of
      LEC or splenic epidermoid cyst over other cystic lesions when the lesion is noted
      in an elderly patient.

PMID- 9530402
TI  - Uterine adenofibroma and adenosarcoma: CT and MR findings.

PMID- 9530403
TI  - Correcting scaling errors in tomographic images using a nine degree of freedom
      registration algorithm.
AB  - PURPOSE: Clinical imaging systems, especially MR scanners, frequently have errors
      of a few percent in their voxel dimensions. We evaluate a nine degree of freedom
      registration algorithm that maximizes mutual information for determining scaling
      errors. We evaluate it by registering MR and CT images for each of five patients
      (patient scaling) and by registering MR images of a phantom to a computer model
      of the phantom (phantom scaling). METHOD: Each scaling method was validated using
      bone-implanted markers localized in the patient images and also intraoperatively.
      The root mean square residual in the alignment of the fiducial markers [fiducial
      registration error (FRE)] was determined without scale correction, with patient
      scaling, and with phantom scaling. RESULTS: Each scaling method significantly
      reduced the average FRE (p < 0.05) for MR to CT registration and for MR to
      physical space registration, indicating that voxel scaling errors were reduced.
      The greater reduction in scaling errors was achieved using the phantom scaling
      method. CONCLUSION: We have demonstrated that a nine degree of freedom
      registration algorithm that maximizes mutual information can significantly reduce
      scaling errors in MR.

PMID- 9530404
TI  - Enhancement of MR images using registration for signal averaging.
AB  - PURPOSE: With the advent of noninvasive neuroimaging, a plethora of digital human
      neuroanatomical atlases has been developed. The accuracy of these atlases is
      constrained by the resolution and signal-gathering powers of available imaging
      equipment. In an attempt to circumvent these limitations and to produce a high
      resolution in vivo human neuroanatomy, we investigated the usefulness of
      intrasubject registration for post hoc MR signal averaging. METHOD: Twenty-seven
      high resolution (7 x 0.78 and 20 x 1.0 mm3) T1-weighted volumes were acquired
      from a single subject, along with 12 double echo T2/proton density-weighted
      volumes. These volumes were automatically registered to a common stereotaxic
      space in which they were subsampled and intensity averaged. The resulting images
      were examined for anatomical quality and usefulness for other analytical
      techniques. RESULTS: The quality of the resulting image from the combination of
      as few as five T1 volumes was visibly enhanced. The signal-to-noise ratio was
      expected to increase as the root of the number of contributing scans to 5.2, n =
      27. The improvement in the n = 27 average was great enough that fine anatomical
      details, such as thalamic subnuclei and the gray bridges between the caudate and
      putamen, became crisply defined. The gray/white matter boundaries were also
      enhanced, as was the visibility of any finer structure that was surrounded by
      tissue of varying T1 intensity. The T2 and proton density average images were
      also of higher quality than single scans, but the improvement was not as dramatic
      as that of the T1 volumes. CONCLUSION: Overall, the enhanced signal in the
      averaged images resulted in higher quality anatomical images, and the data lent
      themselves to several postprocessing techniques. The high quality of the enhanced
      images permits novel uses of the data and extends the possibilities for in vivo
      human neuroanatomy.

PMID- 9530405
TI  - Aunt Minnie's corner. Lingual thyroid.

PMID- 9530407
TI  - Somatic cell counts, international marketing debated at NMC meeting.

PMID- 9530406
TI  - Dual-phase helical CT of nonfunctioning islet cell tumors.
AB  - PURPOSE: The aim of this study was to evaluate the utility of dual-phase imaging
      in the assessment of nonfunctioning islet cell tumors (NFITs). METHOD: Six
      patients with histologically and biochemically proven NFIT were evaluated by
      arterial and portal venous dual-phase helical CT. Scan delay was 20 s for the
      arterial phase and 70 s for the portal phase. Each phase was assessed by
      consensus reading and specifically evaluated for tumor conspicuity, hepatic
      metastases, vascular encasement by tumor, and presence of lymphadenopathy.
      RESULTS: Overall, tumor conspicuity was greater in the arterial phase (5/6) than
      in the portal venous phase (1/6) with a mean tumor/normal pancreas attenuation
      difference of 31.8 HU in the arterial phase compared with 19.2 HU in the portal
      venous phase. The arterial phase detected a total of 17 liver metastases compared
      with 9 seen in the portal phase. Lymph node enlargement was noted in three
      patients, which, although visible in both phases, was more easily discernible in
      the arterial phase. Venous encasement by tumor was better evaluated on the
      delayed portal venous phase than the arterial phase. CONCLUSION: Dual-phase
      helical CT scanning leads to improvement in the detection and staging of NFITs.

PMID- 9530408
TI  - Assessing pain in dogs.

PMID- 9530409
TI  - New model suggested for veterinary education.

PMID- 9530410
TI  - Dealing with unethical veterinarians.

PMID- 9530411
TI  - Are nylon cable ties safe?

PMID- 9530412
TI  - Are nylon cable ties safe?

PMID- 9530413
TI  - Controlling cat populations.

PMID- 9530414
TI  - Controversy regarding vaccination procedures for cats.

PMID- 9530415
TI  - Controversy regarding vaccination procedures for cats.

PMID- 9530416
TI  - Controversy regarding vaccination procedures for cats.

PMID- 9530417
TI  - What is your diagnosis? Carpus valgus and hypoplasia of the carpal bones in a
      foal.

PMID- 9530418
TI  - Theriogenology question of the month. Confirmation of fetal viability via
      ultrasonography.

PMID- 9530419
TI  - Financial impact of the 1995 outbreak of vesicular stomatitis on 16 beef ranches
      in Colorado.
AB  - OBJECTIVE: To determine financial impact of an outbreak of vesicular stomatitis
      in the San Luis Valley of southern Colorado. DESIGN: Survey and financial
      analysis. SAMPLE POPULATION: 16 ranchers whose beef herds were affected by the
      1995 outbreak. PROCEDURE: Information concerning financial effects during the
      outbreak year was collected by personal interview of each rancher and examination
      of financial records. RESULTS: Affected herds ranged from 79 to 956 cows (mean,
      345). Cow case-fatality rates ranged from 0 to 80%, with calf case-fatality rates
      ranging from 0 to 28% and overall case-fatality rates of 0 to 15%. Median
      financial loss was $7,818/ranch and mean financial loss was $15,565/ranch,
      excluding total financial losses associated with sale of calves. Primary
      financial losses for these beef herds were attributed to increased culling rates,
      death of pregnant cows, loss of income from calves, and costs for additional
      labor during the outbreak. Some costs were attributable to a decrease in market
      price for beef and a drought during the year after the outbreak. CLINICAL
      IMPLICATIONS: Financial losses for an outbreak of vesicular stomatitis can be
      attributed to effects of the disease and costs associated with imposed
      quarantines.

PMID- 9530421
TI  - Acute fulminating myasthenia gravis in five dogs.
AB  - Acute fulminating myasthenia gravis (MG) was diagnosed in 5 dogs. Acute
      fulminating generalized MG in dogs is characterized by sudden onset of
      megaesophagus and frequent regurgitation of large volumes of fluid. Generalized
      muscle weakness can worsen and lead to recumbency within days. Despite
      appropriate supportive care, weakness is not alleviated by rest. Respiratory
      failure caused by aspiration pneumonia and loss of strength in muscles involved
      with respiration is a common cause of death. In dogs with acute onset of
      regurgitation, MG should be considered as a differential diagnosis. Clinicians
      should be aware of the risk of rapid progression to quadriparesis if aspiration
      pneumonia develops.

PMID- 9530420
TI  - Granulomatous meningitis caused by Coccidioides immitis in a dog.
AB  - Granulomatous meningitis attributable to Coccidioides immitis was diagnosed on
      postmortem examination in a 4-year-old Border Collie. Clinical signs included CNS
      disease, aspiration pneumonia secondary to a megaesophagus, and otitis externa.
      Central nervous system signs included central vestibular and cranial nerve
      dysfunction. Cerebellar and medullary infiltrates seen on histologic examination
      affected cranial nerves VIII, IX, and X. Despite extensive diagnostics, diagnosis
      was not made antemortem. Analysis of CSF suggested suppurative meningitis, but
      bacteriologic culture results were negative. Coccidioides endospores were
      identified on reexamination of brain tissue. The clinical course of disease and
      rate of Coccidioides immitis infection is variable. Causative agents of
      granulomatous or inflammatory CNS disease may include fungal infection more often
      than is currently suspected.

PMID- 9530422
TI  - Surgical correction of late-onset Budd-Chiari-like syndrome in a dog.
AB  - An 18-month-old dog was examined because of ascites of 1 month's duration.
      Typical causes of ascites, including hepatic failure, heart failure, and protein
      losing enteropathy, were ruled out. The dog's history included being hit by a car
      6 months earlier, and the caudal vena cava had an S shape on thoracic
      radiographs. In addition, the abdominal fluid had a high protein concentration
      and low cellular content. These findings were all consistent with a diagnosis of
      postsinusoidal hypertension secondary to obstruction of hepatic venous outflow
      (Budd-Chiari-like syndrome). During exploratory thoracotomy, the pericardium
      appeared to have been torn from the heart and was partially wrapped around the
      caudal vena cava, causing a constriction. The pericardium was removed and the dog
      recovered without any further complications. Blunt trauma has been previously
      reported to cause kinking of the caudal vena cava and Budd-Chiari-like syndrome
      in dogs; but in these dogs, clinical signs of ascites developed a few days to
      several weeks after the traumatic incident. It appears that, depending on the
      cause of the hepatic venous outflow obstruction, onset of Budd-Chiari-like
      syndrome may be delayed for months.

PMID- 9530423
TI  - Stress responses of horses during a long period of transport in a commercial
      truck.
AB  - OBJECTIVES: To characterize progressive patterns of dehydration, stress
      responses, and water consumption in horses transported long distances in hot
      weather and to evaluate various measurements in detecting dehydration and stress
      in transported horses. DESIGN: Prospective study. ANIMALS: 30 mature, healthy
      horses. PROCEDURE: The following 4 treatment groups were studied: horses that
      were penned and offered water every 5 hours (n = 5), horses that were penned and
      not offered water (5), horses that were transported in a truck and offered water
      every 5 hours (10), and horses that were transported and not offered water (10).
      The study commenced after 6 hours of water deprivation. Every 4 hours, the truck
      returned to the pen area and body weights were measured, physical examinations
      were performed, and blood samples were obtained. During this 1-hour period, water
      was offered to some horses, depending on treatment group. RESULTS: After 24 hours
      of transport, 3 horses were judged unable to continue and the study was
      terminated. Horses that were penned and offered water drank a mean of 38.2 L and
      horses that were transported and offered water drank 20.9 L, but some of the
      latter horses did not drink until after 19 or 24 hours of transport. In horses
      that were transported or penned and not offered water, serum electrolyte
      concentrations were greater than reference range values by 19 hours. Most horses
      that were transported and offered water consumed adequate water to postpone
      severe dehydration beyond 24 hours. CLINICAL IMPLICATIONS: Tame horses in good
      condition and initially deprived of access of water for approximately 6 hours can
      be transported in groups in open trailers during hot, humid conditions for up to
      24 hours before dehydration and fatigue become severe. Rectal temperature and
      appearance of the horses were the most useful measures for determining crisis
      situations.

PMID- 9530424
TI  - Use of laparoscopic equipment to divide abdominal adhesions in a filly.
AB  - Exploratory laparoscopy of the right dorsal portion of the abdominal cavity was
      performed on a Standardbred filly because of signs of mild abdominal pain of 7
      days' duration. On the basis of clinical examination, diagnosis was suppurative
      peritonitis, abdominal adhesions in the area of the right ovary, and right
      displacement and impaction of the pelvic flexure of the ascending colon. During
      laparoscopy, an abdominal adhesion between the right uterine horn, the cecum, and
      the pelvic flexure was identified. The abdominal adhesions were either stretched
      with laparoscopic forceps used as a probe or dissected bluntly with the tips of a
      pair of 10-mm laparoscopic Kelly forceps. Antibiotics were administered for 21
      days after surgery. The horse fully recovered and raced 11 months after the
      surgery.

PMID- 9530425
TI  - Cobalt 60 radiotherapy for treatment of squamous cell carcinoma of the nasal
      cavity and paranasal sinuses in three horses.
AB  - Three adult horses underwent aggressive treatment of squamous cell carcinoma of
      the nasal cavity and paranasal sinuses, using course-fractionated cobalt 60
      radiotherapy. Squamous cell carcinoma of the nasal cavity and paranasal sinuses
      is not commonly diagnosed in horses. Historically, horses with this type of
      neoplasm have not been treated or have undergone some form of surgery. The
      prognosis for long-term survival or cure has been poor. Long-term results of
      cobalt 60 radiotherapy were good to excellent and exceeded those usually reported
      for horses treated surgically. On the basis of these results, use of radiotherapy
      for these neoplasms is recommended.

PMID- 9530426
TI  - Ocular lesions in horses with lymphosarcoma: 21 cases (1977-1997).
AB  - OBJECTIVE: To determine the most common ocular lesions in horses with
      lymphosarcoma. DESIGN: Retrospective study. ANIMALS: 79 horses histologically
      confirmed to have lymphosarcoma. PROCEDURE: Ophthalmic examinations were
      performed by a single individual. RESULTS: 21 of 79 horses had lesions involving
      the eye or ocular adnexa. Infiltration of the palpebral conjunctiva and eyelids
      was the most common lesion (n = 11). Other lesions included uveitis (n = 4),
      corneoscleral masses (2), third eyelid masses (2), and diffuse retrobulbar
      infiltrates (2). CLINICAL IMPLICATIONS: In horses with lymphosarcoma, ocular
      lesions may precede or be more obvious than lymph node enlargement or signs of
      visceral involvement. Early recognition of ocular lesions suggestive of
      lymphosarcoma may allow a more rapid diagnosis of lymphosarcoma in horses.

PMID- 9530427
TI  - Effects of extensive crossfostering on performance of pigs on a farm.
AB  - OBJECTIVE: To compare mortality and growth rates of pigs subjected to continuous
      or limited crossfostering. DESIGN: Prospective study. ANIMALS: 80 liters
      containing 879 pigs. PROCEDURE: In half of the litters, crossfostering was
      limited to the first 2 days of life. In the other litters, pigs were
      crossfostered throughout the lactation period to maintain uniform body weights
      within litters. RESULTS: Restricting crossfostering to the first 2 days of life
      resulted in a 20% increase in body weight at weaning, compared with
      crossfostering throughout the nursing period. Mortality rates did not differ
      between the limited and continuous crossfostering groups. CLINICAL IMPLICATIONS:
      The emphasis placed on reducing variation of body weights within litters is
      unwarranted and veterinarians should advise limiting crossfostering to the first
      2 days of life. Excessive crossfostering late in the nursing period may be
      identified by low within-litter SD of mean body weight.

PMID- 9530428
TI  - Sweet clover poisoning in dairy cattle in California.
AB  - Eight of 600 Holstein heifers and cows died after ingestion of sweet clover
      silage (Melilotus sp) that contained excessive concentrations of dicumarol caused
      by mold infestation. The cattle developed subcutaneous hemorrhages and bled from
      the vagina, became weak, were unable to move, and died. To the best of our
      knowledge, this is the first report of sweet clover poisoning in cattle from
      California and is discussed in light of previous findings in the Midwest and
      Canada. Sweet clover poisoning is caused by dicumarol, a fungal metabolite
      produced from substrates in sweet clover, and is a common livestock problem in
      the Northern Plains and Canada. Sweet clover poisoning should be considered in
      livestock animals with clinical evidence of hemostatic dysfunction, prolonged
      coagulation times, subcutaneous hemorrhages, and hemorrhagic abortions. Definite
      diagnosis of moldy sweet clover poisoning can be accomplished by analysis of
      serum and feed samples for dicumarol concentrations.

PMID- 9530429
TI  - Surgical repair of patellar luxation in llamas: 7 cases (1980-1996).
AB  - OBJECTIVE: To evaluate anatomy of the stifle in llamas and determine outcome of
      llamas that underwent surgery for repair of patellar luxation. DESIGN: Anatomic
      and retrospective study. ANIMALS: 6 llamas with unilateral patellar luxation and
      1 llama with bilateral luxations. PROCEDURE: 6 stifles from llama cadavers were
      dissected to determine anatomy. Medical records were reviewed to identify
      history, procedure, outcome, and complications of llamas that underwent surgery.
      RESULTS: 6 llamas had lateral patellar luxation (including the llama with
      bilateral luxations), and 1 had medial patellar luxation. Six llamas had a
      history of trauma before onset of clinical signs. Two llamas underwent tibial
      tuberosity transposition, but luxation recurred in both and 1 had problems with
      breakage of implants. The other 5 llamas underwent imbrication and release
      procedures; however, luxation recurred in 4 of the 5. Surgery was repeated in 2
      llamas, with successful outcomes. CLINICAL IMPLICATIONS: Results suggest that
      imbrication and release procedures may be useful for correction of patellar
      luxation in llamas without other bony abnormalities. However, long (20 cm)
      imbrication and release incisions are needed for a successful outcome. Use of a
      sling after surgery, to allow a gradual return to weight bearing and exercise,
      may also be important.

PMID- 9530430
TI  - Reptile-associated salmonellosis.

PMID- 9530431
TI  - The effects of patterned breathing and continuous positive airway pressure on
      cardiovascular regulation in healthy volunteers.
AB  - 1. Although the increased heart rate variability in healthy subjects in
      association with slow patterned breathing and continuous positive airway pressure
      is well documented, there is no general agreement regarding the underlying
      mechanism. The arterial baroreceptor stimulation due to greater blood pressure
      variability, the stimulation of pulmonary stretch and low pressure baroreceptors
      can play important role in this phenomenon. 2. In order to assess the interplay
      between blood pressure and heart rate changes we have studied nine healthy
      volunteers (mean age was 22 yrs. range 19-24), by applying 6/min patterned
      breathing, and continuous positive airway pressure of 10 cm of water. ECG and
      finger blood pressure (Finapres 2300) was continuously recorded. The oscillation
      amplitude of R-R intervals were analysed as well as the time and frequency domain
      indexes of heart rate variability. The oscillation amplitude and the
      corresponding frequency domain components of systolic blood pressure were also
      calculated. 3. The forced deep breathing caused significant increase in heart
      rate variability as indicated by time and frequency domain analysis of R-R
      intervals (LF HRV ms2: spontaneous: 777.40 +/- 526.1, patterned breathing 6828.00
      +/- 5468.0). The application of CPAP in the same rhythm during patterned
      breathing resulted in further enhancement in heart rate variability (LF HRV ms2:
      9052.00 +/- 4533.0). The analysis of the same frequency domain components of
      systolic blood pressure showed marked elevation of the total and low frequency
      power during patterned breathing. (LF BPV mm Hg2: spontaneous: 8.24 +/- 6.2,
      patterned breathing: 16.22 +/- 9.7). Applying CPAP with the same breathing
      pattern elicited further significant increment in systolic blood pressure
      fluctuation (LF BPV mm Hg2: deep breathing + CPAP: 27.11 +/- 9.8). The baroreflex
      sensitivity as calculated from spontaneous HR and BP sequences was 11.66 +/- 2.9
      at baseline and increased to 17.66 +/- 6.1 and changed to 15.22 +/- 3.2 with the
      addition of patterned breathing and CPAP, respectively. 4. Our findings indicate
      that the heart rate and blood pressure responses to slow patterned breathing may
      be interpreted as consequences of an altered baroreflex sensitivity. In contrast
      the active breathing with CPAP exerts mechanical effects which in turn present an
      augmented systemic baroreflex trigger, however, the baroreflex sensitivity
      remains unchanged.

PMID- 9530432
TI  - Effect of neonatal triiodothyronine (T3) treatment (hormonal imprinting) on the
      sexual behavior of adult rats.
AB  - Neonatal treatment with triiodothyronine increased the mounting and decreased the
      intromission of male rats. Number of inactive rats and number of ejaculations
      were not changed. In females a non-significant increase of Meyerson index was
      observed. Considering earlier results, the experiment demonstrates that neonatal
      T3 treatment can influence different receptors for life. The results also
      supports earlier observations on the sexual behavioral effect of perinatal
      treatment with molecules being structurally different from steroids however able
      to bind to receptors of the steroid receptor superfamily.

PMID- 9530433
TI  - Glomerular prostanoid production is modified by plasma samples of hypertensive
      and diabetic patients.
AB  - The autocrin-paracrin prostanoid system plays a major role in the enhancement or
      inhibition of renal tissue damage. Our hypothesis was that there might be
      circulating factors in the plasma with a capability to modify renal (glomerular)
      prostanoid synthesis. We measured the synthesis of prostacyclin 1-2 (PGI2) and
      thromboxan A-2 (TxA2) of isolated glomeruli, incubated in plasma samples obtained
      from hypertensive and diabetic (NIDDM) patients. It was found that these plasma
      samples decreased the renal PGI2/TxA2 ratio, mostly by decreasing glomerular PGI2
      synthesis and, to a lesser extent, increasing the synthesis of TxA2. Our results
      demonstrate that circulating factors in hypertension and diabetes might play a
      role in renal damage seen in these conditions.

PMID- 9530434
TI  - Oxidative stress in experimental diabetes induced by streptozotocin.
AB  - It is known that streptozotocin (STZ) penetrating into the organism generates
      nitrogen monoxide (NO). Therefore, it is justified to presume, that in beta-cell
      destruction thereby induced, peroxinitrit resulting from NO and superoxide (O2-)
      reaction has an important role. It has also been studied how pro- and antioxidant
      systems change in STZ induced experimental diabetes in rat organs. Beside pro-
      and antioxidant systems of plasma and red blood cell hemolysates, changes in
      homogenates of the following organs were studied: liver, kidney, heart, lungs,
      spleen, brain, muscles and pancreas. We tested and compared antioxidant enzymes
      (superoxide dismutase-, glutathione peroxidase- and catalase activities)
      glutathione reductase activity regenerate reduced glutathione (GSH). The
      oxidized, reduced glutathione values and lipid peroxidation changes were
      measured. From our studies it has appeared that STZ treatment generally induces
      an oxidative predominance in tissues. Changes in this model thereby, can be
      compared to changes occurring in type 1 human diabetic patients.

PMID- 9530435
TI  - Prostaglandin E receptors in myometrial cells.
AB  - Prostaglandins (PGs) exert their effects via binding to specific cell surface
      receptors and influencing second messenger systems through G-proteins. PGE2 may
      interact with at least four receptor subtypes (EP1, EP2, EP3, EP4), each showing
      different pharmacological profiles. The second messengers calcium, inositol
      phosphates (InsPs) and cyclic nucleotides play decisive roles in uterine
      contractility. The question in this investigation was, which EP receptors, G
      proteins and second messenger systems transmit PGE2 induced signals in human
      myometrium. We have measured changes in InsPs and cAMP formation and also in
      intracellular calcium concentration ([Ca2+]i) induced by PGE2 and receptor
      subtype selective analogues in cultured human myometrial cells. PGE2 increased
      cAMP level and this effect was shared by the EP2 receptor subtype selective
      agonist Butaprost and by Misoprostol (EP3 > EP2 > EP1). Sulprostone (EP3 > EP1)
      did not stimulate adenylyl cyclase activity per se, but inhibited forskolin
      stimulated adenylyl cyclase in a pertussis toxin (PT) sensitive way. PGE2,
      GR63799X (EP3 selective), Sulprostone and Misoprostol activated phospholipase-C
      (PLC), this effect was resistant to PT treatment. PGE2 also elevated [Ca2+]i from
      the resting level of 60-90 nM up to 350 nM. Low concentrations (1-300 nM) of PGE2
      increased [Ca2+]i without PLC activation. The selective EP1 inhibitor AH6809,
      Nifedipine, Verapamil and PT treatment inhibited this effect of PGE2. In cultured
      human myometrial cells PGE2 interacts with EP1 receptors, which elevate [Ca2+]i
      independently from PLC, but involving a Gi protein and plasmamembrane calcium
      channels; EP2 receptors which stimulate adenylyl cyclase; EP3A receptors, which
      inhibit adenylyl cyclase activity through Gi activation and EP3D receptors which
      activate PLC through a PT-insensitive pathway and also elevate [Ca2+]i.

PMID- 9530438
TI  - Effects of lormetazepam on glycemia and serum lipids in hyperlipidemic rats.
AB  - Lormetazepam (N-methyllorazepam) administered intraperitoneally to rats rendered
      hyperlipidemic by Triton WR-1339 induced an elevation of blood glucose level at
      all investigated doses. It brought about significant reduction of serum total
      lipids, total cholesterol and triglycerides. The dose-response relationship was
      bell-shaped. However, it presented two peaks, differing from the responses to
      other benzodiazepines (BZD) which were characterized by only one peak.

PMID- 9530437
TI  - Basal and stress induced concentrations of adrenal gland catecholamines and
      plasma ACTH during aging.
AB  - Basal and stress levels of catecholamines (CA) in the adrenal glands, and
      circulatory levels of adrenocorticotropic hormone (ACTH) were examined in female
      Wistar rats aged 1, 3, 10 and 24 months. Our data showed reduction in basal
      dopamine (DA) concentration in adrenal glands and an increase in this
      catecholamine in response to stress at all ages (1, 3, 10, 24 months). The
      greatest levels of basal norepinephrine (NE) and epinephrine (E) concentrations
      in the adrenal glands were noted in intact rats at the age of 24 months. On the
      other hand, the stress response of NE and DA had a tendency to fall, reaching
      basal values at the age of 10 and 24 months of age. Basal circulatory levels of
      ACTH showed a reduction with age. The stress response of ACTH was reduced in
      animals aged 10 and 24 months. Reduced basal values of adrenal DA and increased
      NE and E values, suggest that there is increased adrenomedullar activity at the
      age of 24 months. On the other hand, the reduced or even absent stress response
      of NE and E observed in the adrenals, in 10 and 24 months old rats, may be of
      interest in considering the ability of these animals for adaptation. Basal and
      stress values of plasma ACTH are significantly reduced with the onset of
      senescence in female rats.

PMID- 9530440
TI  - [Short scientific papers in English: swifter publication and worldwide
      distribution for short scientific papers].

PMID- 9530436
TI  - The effect of adrenoreceptor antagonists and agonists on LHRH release from the
      stalk-median eminence in the pig.
AB  - A release of radio-immunoassayable LHRH from the stalk-median eminence of
      neonatal piglets and prepubertal gilts was measured using an in vitro incubation
      system. The stalk-median eminence was collected from one-week-old male (n = 19)
      and female (n = 21) piglets and from 6-month-old prepubertal ovariectomized gilts
      given oestradiol benzoate (20 micrograms/kg b.w.; n = 52) or left untreated
      (control; n = 25) 30 or 68 h before slaughter. Each vial, containing the stalk
      median eminence in 2 ml of Krebs-Ringer bicarbonate buffer, was incubated for 30
      min, followed by 30 min incubations during which either basal release or the
      effect of adrenoreceptor antagonists and agonists on LHRH output was evaluated.
      There were no differences between the basal release of LHRH (x +/- SEM; pg/ml)
      from the stalk-median eminence of male (65.5 +/- 9.8) and female (66.3 +/- 9.6)
      newborn piglets. The addition of propranolol (10(-6) M) caused a 250% increase in
      LHRH release from the stalk-median eminence explants of neonatal males (p = 0.08)
      and females (p < 0.05). Neither norepinephrine nor phentolamine affected LHRH
      release from the stalk-median eminence of newborn males and females. The basal
      release of LHRH (pg/ml) from the stalk-median eminence explants collected from
      ovariectomized gilts given oestradiol benzoate 30 and 68 h before slaughter or
      left untreated was similar (147.5 +/- 36.1, 236.4 +/- 77.7 and 202.0 +/- 41.6,
      respectively). Propranolol evoked a significant increase in LHRH secretion from
      the stalk-median eminence in the control group, but not in the groups given
      oestradiol benzoate. Norepinephrine (10(-6) M) increased LHRH release from the
      stalk-median eminence collected from the control animals, 30 h and 68 h after
      oestradiol benzoate treatment by 48, 78 and 73 percent, respectively.
      Phentolamine (10(-6) M) did not affect LHRH release from the stalk-median
      eminence in control animals and ovariectomized gilts primed with oestradiol
      benzoate. Urapidil (10(-6) M, alpha 1-adrenoreceptor antagonist) did not affect
      the basal LHRH release from the stalk-median eminence of gilts from the control
      group and group slaughtered 30 h after oestradiol benzoate treatment, but caused
      a rapid increase of LHRH release from the stalk-median eminence 68 h after
      oestradiol benzoate treatment. Phenylephrine (10(-6) M) did not affect LHRH
      output from the stalk-median eminence collected at various time periods after
      oestradiol benzoate administration in vivo. These results suggest that in pigs,
      nerve terminals releasing LHRH at the stalk-median eminence level are sensitive
      to adrenergic stimulation or inhibition and that the adrenergic system can be
      modulated by estrogens in the prepubertal gilts.

PMID- 9530439
TI  - The effects of the intraperitoneal administration of midazolam on blood glucose
      level and serum lipids in streptozotocin-induced diabetes in rats.
AB  - In male Wistar rats rendered diabetic by streptozotocin administration, the
      intraperitoneal (i.p.) injection of midazolam (2.5-5.0 and 10 mg/kg) induced a
      significant reduction of hyperglycemia and hyperlipidemia. The plasma
      immunoreactive insulin level was slightly, but significantly increased. The
      lethality was diminished.

PMID- 9530441
TI  - [The sympathetic nervous system and pain].

PMID- 9530442
TI  - [Pain syndromes with causal participation of the sympathetic nervous system].
AB  - The efferent sympathetic nervous system is organized into subsystems that
      innervate and regulate via separate peripheral sympathic pathways the different
      autonomic target organs. This review discusses mechanisms through which this
      efferent system may be causally involved in the generation of pain. Clinical pain
      syndromes in which this may be the case are "complex regional pain syndromes"
      (CRPS) type I (previously reflex sympathetic dystrophy) and type II (recently
      causalgia). The "sympathetically maintained pain" (SMP) is a symptom (and not a
      clinical entity) that can principally also be present in other pain syndromes. An
      explanatory hypothesis, which may explain the clinical phenomenology of CRPS
      (different types of pain, swelling, autonomic, motor and trophic changes) and the
      mechanisms involved, is described and discussed. This hypothesis consists of
      different components that either have been tested and verified experimentally or
      which are still hypothetical. The hypothesis consists of changes in the primary
      afferent (nociceptive and non-nociceptive) neurones (sensitization, ectopic
      impulse generation) and of the neurones in the spinal cord (preferentially in the
      dorsal horn) which are secondary consequences of the changes in the primary
      afferent neurones ("central sensitization"). These changes are not specific for
      SMP. The centerpiece of the hypothesis is a positive feedback circuit that
      consists of the primary afferent neurones, spinal cord neurones, sympathic
      neurones and the pathologic sympathetic-afferent coupling. This coupling can
      occur directly via noradrenaline (or possibly another substance) at different
      sites of the afferent neurone (at the lesion site, remote from the lesion site in
      the periphery and in the spinal ganglion). The direct coupling requires that the
      afferent neurone expresses adrenoceptors. Indirect coupling can occur via the
      vascular bed or otherwise, e.g. by changes of the neurovascular transmission. The
      activity in the sympathetic neurones to the affected extremity can change. This
      change does not consist of a generalized increase of sympathetic activity but of
      a change of the reflexes (e.g., thermoregulatory and nociceptive reflexes). From
      this follows that the pathophysiologal processes operating in CRPS may occur at
      four levels of integration that interact with each other: effector organ,
      peripheral afferent and sympathetic neurone, spinal cord, supraspinal centres.
      Recent experimental investigations on rats show that the sympathetic nervous
      system is possibly also causally involved in the generation of inflammation and
      inflammatory pain. The mechanisms by which this occurs are different from those
      operating in SMP during CRPS.

PMID- 9530444
TI  - [Validation of the acute physiology and chronic health evaluation (APACHE) III
      scoring system and comparison with APACHE II in German intensive care units].
AB  - OBJECTIVES: The aim of the study was to systematically validate the APACHE III
      scoring system concerning severity of illness classification and prediction of
      hospital mortality. Such data have not yet been determined in a large population
      of critically ill patients in germany. METHODS: 531 patients (ICU stay > 4 hours)
      were prospectively and consecutively investigated. The day-1-scores and risk-of
      death predictions of APACHE III and APACHE II were determined. A comparison was
      performed between both scoring systems, and the correlation with the observed
      hospital mortality was examined. RESULTS: For both main validation criteria, as
      were discrimination (areas under the ROC-curves: APACHE III 0.873; APACHE II
      0.859) and calibration (goodness-of-fit testings; p > 0.05), both scoring systems
      provided satisfying results concerning hospital mortality, no system showing a
      significantly superior performance. Compared to the observed hospital mortality
      (13.4%), the prediction of APACHE III (13.2%) was extremely accurate, whereas the
      prediction of APACHE II was higher (16.8%). The standard (mortality index not
      significantly < or > 1.0) provided by APACHE III was fulfilled, while the
      standard given by APACHE II was surpassed. The mean scores and the mean risk-of
      death predictions for non-survivors were significantly higher compared to
      survivors (P < 0.001). The individual score values of both systems were found to
      have a strong correlation (r = 0.922). CONCLUSIONS: APACHE III (like APACHE II)
      provides a sufficient severity of disease classification and accurately predicts
      overall hospital mortality in a representatively large german population of a
      medical ICU. Therefore APACHE III can be regarded as validated for the use in
      comparable german ICUs. For use as a standard the more recently introduced APACHE
      III seems to be superior to the established but older APACHE II. However, each
      user will--depending on the particular questions to be addressed--carefully have
      to evaluate, if the improvement of prognostic accuracy really justifies the
      increased amount of workload necessary for calculating APACHE III score and risk
      prediction.

PMID- 9530443
TI  - [Health-related quality of life. Long-term survival in patients with ARDS
      following extracorporeal membrane oxygenation (ECMO)].
AB  - Treatment of severe acute respiratory distress syndrome (ARDS) with
      extracorporeal membrane oxygenation (ECMO) can be lifesaving but requires maximal
      use of intensive care resources over prolonged periods of time, resulting in high
      costs. Little is known about the health-related quality of life (HRQL) in long
      term survivors. This case-controlled retrospective study was designed to assess
      the health-related quality of life in long-term survivors of ARDS and ECMO
      therapy. METHODS: 14 long-term survivors of ARDS (APACHE II score = 24, Lung
      Injury Score = 3.25, median values) treated using ECMO between 1992 and 1995
      (median time interval between data collection and discharge from the ICU 16
      months) and 14 ARDS-patients conventionally treated during the same period (group
      I) were identified and completed the SF-36 Health Status Questionnaire (Medical
      Outcome Trust, Boston, USA). 14 healthy subjects (group II) were drawn at random
      from a large data base generated to provide normal values for the SF-36 in a
      German population. All three groups were comparable with respect to sex and age.
      RESULTS: Long-term survivors of ECMO-therapy reported significant reductions in
      physical functioning when compared with patients treated by mechanical
      ventilation alone (group I, -12.5%, p < 0.05) and with healthy controls (group
      II, -50%, p < 0.05) and showed a higher incidence of chronic physical pain (+5%
      and +24%, respectively, p < 0.05). There were no differences with regard to the
      mental health dimensions of the SF-36 (e.g. vitality, mental health index or
      social functioning) between ECMO-patients and all controls. Nine patients (64.3%)
      from the ECMO group versus all patients treated conventionally (group I) had full
      time employment (p = 0.46, Chi2 test). CONCLUSIONS: The majority of long-term
      survivors of ECMO-treatment show good physical and social functioning, including
      a high rate of employment. The more aggressive approach of ECMO-therapy and a
      possibly more severe underlying disease process may explain impairments in health
      related quality of life outcomes after ECMO-treatment. Despite these limitations,
      long-term survivors of ECMO-therapy are able to reach a highly satisfactory
      health-related quality of life.

PMID- 9530445
TI  - [The effect of temperature and humidity on breath samples. Measurement of breath
      ethanol concentration in artificially respirated patients].
AB  - When looking for the possible cause of distortions in values measured for the
      determination of breath ethanol concentration (BEC) in artificially respirated
      patients, consideration must be given to the humidity and temperature of the gas
      examined. In the present study, the effects of humidified and warmed and of dry
      and cold air on the accuracy of a newly developed BEC measuring device, as
      compared to a reference model and to a conventional system, were examined in a
      lung model. METHODS: A temperature-regulated pediatric incubator was used
      containing a 10 I gas reservoir and a breath humidifier with temperature
      regulated water bath. This setup provided constant temperature and humidity in
      the gas examined during measurement period. In the 'expiration' the air was
      directed from the breath humidifier through a measuring unit via a 'mouthpiece'
      into the reference system (Alcotest 7110, Drager Inc., Lubeck) and then out. The
      measuring unit consisted of sensors for the temperature and relative humidity,
      and of a connector for the three sample extraction systems (PES). PES I was the
      conventional system with a 100-cm gas-sample pipe (Alcomed 3010), PES II the
      newly developed system (AlcoMed 3011, both from Envitec, Wismar) with a 10-cm gas
      sample pipe, and PES III with a 20-cm heated gas-sample pipe. During
      'inspiration' 2 l of air was fed into the system to rinse the measuring unit and
      to fill the reservoir. 61 measurements were performed with dry and cold air, and
      71 with humidified and warmed air, in the course of which the ethanol
      concentration was increased from 0 to 1.5/1000. Data were evaluated using
      regression analysis and the Bland & Altman method. RESULTS AND CONCLUSIONS: The
      constancy of the values set for temperature, relative humidity and absolute
      humidity in the lung model was given for all measurements. In the dry and cold
      air, the results from all three test systems coincided almost perfectly with the
      reference values. The measured BEC in the humidified and warmed air using sample
      extraction systems II and III corresponded to a high degree with the reference,
      while in the case of PES I, only a moderate linear correlation was achieved. The
      temperature and humidity of the expired gas during artificial respiration
      influence the gas samples extracted for the purposes of BEC measurement. Newly
      developed sample-extraction systems II and III coincide with the reference
      system, even under respiration-simulated gas conditions.

PMID- 9530446
TI  - [The difficult intubation. The value of BURP and 3 predictive tests of difficult
      intubation].
AB  - The value of BURP (= backwards-upwards-rightwards-pressure of the larynx) was
      tested as a improvement of the visualisation of the larynx. Simultaneously we
      wanted to assess the value of different predictive tests of a difficult
      intubation, which are easy to perform as bedside tests. PATIENTS AND MATERIAL:
      1993 patients of all different surgical clinics in a tertiary care hospital in
      Switzerland were tested, the complete anaesthesiological staff was involved. We
      registered the original Mallampati classes, the thyromental distances of Patil
      and Frerk and the difference of the jugulomental distances in maximally reclined
      and neutral head position according to Chow. Every anaesthetist also noted his
      personal, subjective opinion of a possible difficult intubation. Under optimal
      conditions for intubation we assessed the grade of laryngoscopy according to
      Wilson and applied BURP if the grade was 3 or higher. Both laryngoscopic grades
      and the difficulty of intubation were noted. RESULTS: In our study we found 12.5%
      awkward (Wilson G3-G5) and 4.7% difficult (Wilson G4-G5) laryngoscopies. These
      could be changed with BURP into 5.0% and 1.9% respectively. With BURP we found
      1.8% of difficult intubations. During our study we did not find any patients,
      whom we could not intubate either with a mandrin inside the tube or with help of
      the fiberoptic. The relation between sensitivity and specificity was in all
      single predictors and in two combinations very low. Our personal subjective
      predictions proofed to be better, but the rate of false negatives was too high
      for clinical use. CONCLUSION: BURP is a valuable method for rendering the
      majority of difficult laryngoscopies into easy ones. It is very easy to learn and
      does not need any additional equipment. Three commonly used and recommended
      predictive tests of the difficult intubation proofed to be of little use in
      clinical practice.

PMID- 9530447
TI  - Assessment of intrathoracic blood volume. Thermo-dye dilution technique vs single
      thermodilution technique.

PMID- 9530448
TI  - [Causes of failure and dangers in the use of motor driven infusion pumps.
      Accidental closure of the infusion system].
AB  - Syringe drivers are used in anaesthetics, intensive care and emergency medicine
      to deliver small volumes of highly potent drugs with continuous, constant and
      reproducible flow. For early recognition of interruptions of the drug delivery
      caused by occlusion of the infusion system, an alarm is triggered as soon as the
      system pressure exceeds a certain limit. The sensitivity of this alarm depends on
      the flow rate, type-specific cut-off pressure and the elastic parameters of the
      infusion system. The sudden release of pressure built up in the system after
      occlusion occurred can cause delivery of an uncontrolled drug bolus and hence an
      additional hazard. METHODS: Six syringe drivers that are widely used in clinical
      practice were tested for alarm delay and bolus delivery in the event of an
      occlusion in the system. First, the alarm pressures at flow rates of 10, 50 and
      100 ml/h were measured. Then the alarm delay time and bolus volumes post
      occlusion were assessed, using a basic infusion system (syringe + single infusion
      set). Finally, several alterations to the system like extension, tap battery with
      germ filters or branching were made and their impact on alarm delay and bolus
      volume measured. RESULTS: Because of the great differences in alarm pressures
      between the devices tested, there were marked differences in the alarm delay at
      same flow rates. Predictably, there was an indirect proportional link between
      alarm delay and flow rate. Using the basic infusion system, alarm delays between
      23 s and 143 min were measured. In two of the tested syringe drivers, a pressure
      release mechanism is activated with the pressure alarm, which prevented bolus
      application. In the other devices, release of the pressure in the occluded system
      caused boli of 0.5-7 ml. Variations in the actual syringe volume and insertion of
      a second connection tube had no impact on alarm delay and bolus volume. Tap
      batteries, parallel running syringe drivers or trapped air in the system,
      however, caused marked increase in both alarm delay (107%) and bolus volume
      (+147%). DISCUSSION: Unidentified occlusions of the system cause grave
      malfunctioning of syringe drivers. While applying highly potent drugs, the
      discontinuation of drug delivery with subsequent bolus application can cause
      vital danger to the patient. As a result of the significant time delays in the
      pressure alarms, the devices tested do not provide sufficient protection against
      unrecognized system occlusion. Syringe drivers with adjustable alarm pressure can
      be set close to the actual infusion pressure. A further important point is that
      one should aim at a reduction in the elastic properties of the infusion set
      because of the great impact on alarm delay and bolus volume.

PMID- 9530449
TI  - [Current practices in anesthesia for cesarean section in german university
      clinics. Results of a survey in the year 1996].
AB  - Obviously there is a world-wide trend towards regional anaesthesia for caesarean
      section (CS). Data on the current practice in Germany are lacking. METHODS: In
      1996 questionnaires on obstetric anaesthesia were mailed to all University
      departments of anaesthesia. RESULTS: All 38 University Hospitals with obstetric
      units replied (100%). Mean annual delivery rate was 1156 with a mean CS-rate of
      24%. For scheduled CS the University departments used general anaesthesia in most
      cases (60%), followed by epidural (31%) and spinal anaesthesia (9%). General
      anaesthesia was predominantly used for more urgent (87%) or emergency deliveries
      (99%). Spinal anaesthesia was offered to patients as an option of anaesthesia for
      CS in 16 of 38 departments, epidural anaesthesia in 36 of 38. The majority of
      university hospitals (22 of 38) performed more than 25% of their CS in epidural
      anaesthesia; 14 departments had a ratio of at least 50% of regional anaesthesia.
      28 of 32 centres administered some kind of acid aspiration chemoprophylaxis as a
      routine management. Special devices for the management of a difficult airway were
      provided in 61% of the hospitals within the delivery unit. In 70% the
      anaesthesiologist was responsible for the postoperative pain management following
      CS. CONCLUSION: A significant trend towards regional anaesthesia for CS has taken
      place in German university hospitals: According to a former survey regional
      anaesthesia was used in less than 10% of CS in 1977, whereas in the current
      evaluation from 1996 this figure was significantly higher (40%). Nevertheless,
      compared to other countries the rate of general anaesthesia still is rather high.

PMID- 9530450
TI  - [Karl E. Hammerschmidt. Humanist, natural scientist and pioneer in anesthesia].
AB  - Karl Eduard Hammerschmidt was born in Vienna in 1801. There are indications that
      after studying law he passed on to studies in medicine and surgery in Vienna,
      though it has to be said there is no trace of his attaining any qualification.
      After this he worked in various scientific sectors and in recognition of his
      achievements he was accepted as a member of the Kaiser Leopold Academy of
      Researchers in Natural Sciences in Bonn. From February 1847 to March 1848 he
      induced numerous general anaesthetics with ether, working with Dr. J. Weiger, a
      dentist in Vienna. On 11 July 1847 he published preliminary statistics based on
      1560 dental operations performed under ether anaesthesia and also on numerous
      experiments performed on himself and investigations conducted with ether in
      animals and in healthy subjects. From the viewpoint of scientific research into
      and widening of the applications of ether anaesthesia, his most meritorious
      achievements include the early publication of a staging classification for ether
      anaesthesia, the introduction of an anaesthetic protocol for patients that also
      lent itself to data recording for statistical purposes and the early realization
      that the ability to hear is retained for a very long time during anaesthesia. In
      1848 Hammerschmidt was obliged to flee to Istanbul by way of Hungary because of
      his involvement in the October Revolution. Once there, he continued to work as a
      doctor and later became Professor of Medicine at the University of Istanbul. He
      converted to Islam, taking the name of Abdullah Bey, and also became a colonel in
      the Turkish army. He was one of the founders of the Red Crescent, the
      humanitarian sister organization of the Red Cross, and the Turkish Post
      commemorated this with the issue of a stamp honouring him when the organization
      celebrated the centenary of its formation in 1968. In 1869 the Hapsburg dynasty
      also honoured him with orders and distinctions. He died in Istanbul in 1874 as a
      highly esteemed personage.

PMID- 9530451
TI  - [The importance of quality of whole blood and erythrocyte concentrates for
      autologous transfusion. Reply to the remarks of V. Weisback and R.Eckstein
      (Anaesthesist (1997) 46:459-461) and the work of R. Karger and V. Kretschmer
      (Anaesthesist (1996)] 45:694-707.

PMID- 9530452
TI  - [Reply to the remarks of A. Lorentz et al].

PMID- 9530453
TI  - [Patient positioning-kinetic therapy in intensive medicine].

PMID- 9530454
TI  - [Intubation anesthesia and nursing].

PMID- 9530455
TI  - [Pre-anesthetic fluids and nutritional support?].

PMID- 9530456
TI  - [Codes, guidelines, standards--help or hindrance].

PMID- 9530457
TI  - ["Codes, guidelines, standards". Risk or chance for the doctor or patient ].
AB  - As far as the law concerning liability is concerned, guidelines, codes of
      practice, and medical standards are not contrasting concepts, nor do they
      indicate material differences; instead, those terms describe more or less
      precisely the care that a physician is required to exercise when treating
      patients and that a judge is required to assess in a trial. Guidelines, codes of
      practice, and standards thus take effect not directly, but indirectly, in that
      both physician and judge retain a certain discretion in making decisions in a
      particular case. The current obsession with guideline--primarily based on
      economic considerations and present in all specialist areas--together with the
      increasingly detailed rules that are being issued, carries the risk that to
      medical profession may of its own doing become too restricted, that physicians
      will become limited in their choice of treatment, and that the criteria by which
      liability is assessed will become stricter, thus increasing the physician's risk
      of being held liable under civil or criminal law. We need to prevent a
      development taking place in which "medical standards" become "standardized
      medicine", leading to a situation in which only what is stipulated in the form of
      a guideline or a code of practice will be paid for (and hence only that can be
      done).

PMID- 9530458
TI  - [Quality of pain management in preclinical care of acutely ill patients].
AB  - The aim of this study was to evaluate the quality of pain management in
      prehospital emergency care and to get more information about the administration
      of analgesics in prehospital patients. METHODS: Patients with painful diseases or
      injuries who had been brought to Munich hospital's were included in the study.
      Immediately after having reached the hospitals' emergency department, they were
      evaluated using a 101-point visual analogue scale for the severity of pain at
      four predefined periods. Information about the patient, the diagnosis, and the
      analgesic treatment used by the emergency teams were drawn from the patient's
      chart. RESULTS: A total of 462 patients were included in the study. The mean pain
      score on arrival of the emergency team was 64 points; 36.5% of the patients were
      treated with analgesics. In 28.1% the emergency team tried to reduce pain through
      external measures (i.e., setting of fractures). In 35.3% there was no therapeutic
      intervention. In cases in which analgesic therapy was initiated, a definite
      reduction in pain was achieved during emergency care. Visual analogue scores
      decreased from 70 points at the beginning to 29 points at arrival to the
      hospital's emergency department. Analgesics were most frequently used for
      patients with cardiopulmonary diseases (47.2%), followed by patients with
      traumatic accidents (35.5%) and patients with acute abdominal pain (25.2%). Of
      the analgesics, opioids were given most frequently (87.0%). Nonopioid analgesic
      agents were used in 32.1%. The results of our investigation demonstrate that in
      many cases the administration of analgesics is not individualized to the patients
      needs. CONCLUSION: During the prehospital period of emergency care many patients
      suffer from severe pain. The development of patient-oriented concepts concerning
      pain management could contribute to improvement of pain therapy in prehospital
      emergency medicine.

PMID- 9530459
TI  - [Remifentanil-propofol anesthesia in vertebral disc operations: a comparison with
      desflurane-N2O inhalation anesthesia. Effect on hemodynamics and recovery].
AB  - OBJECTIVE: To ascertain whether there is a difference between total intravenous
      anaesthesia with propofol (P) and remifentanil (R) and inhalational anaesthesia
      with desflurane (D) and nitrous oxide (N) with regard to haemodynamic reactions,
      recovery profile and postoperative analgesic demand in patients scheduled for
      elective microsurgical vertebral disc resection. METHODS: 50 patients (ASA I-II,
      18-65 years) were randomly assigned to receive total intravenous anaesthesia with
      propofol and remifentanil or inhalational anaesthesia with desflurane and nitrous
      oxide. After standardised induction of anaesthesia in both groups (1 microgram.kg
      1 remifentanil, 1.5 mg.kg-1 propofol 0.1 mg.kg-1 cisatracurium), anaesthesia was
      maintained in the D/N group with desflurane in 50% N2O. The patients of the P/R
      group received a constant infusion of 2 mg.kg-1.h-1 propofol and a constant
      infusion of 0.5 microgram.kg-1.min-1 remifentanil, which was reduced after 15 min
      by 50%. The administration of desflurane and the infusion of the anaesthetics
      were adjusted to maintain a surgical depth of anaesthesia. At the end of surgery
      the anaesthetics were discontinued and early emergence from anaesthesia was
      assessed by measuring time to spontaneous ventilation (VT > 4 ml/kg), tracheal
      extubation, opening of the eyes and stating correct name and data of birth. The
      frequency of analgesics and total demand for analgesics were determined using
      patient-controlled analgesia and recorded for 2 h postoperatively. In addition
      the pain level of the patients was measured on a visual analogue scale and the
      incidence of postoperative shivering, nausea and vomiting was noted. RESULTS:
      Patients anaesthetised with desflurane responded to tracheal intubation and skin
      incision with increasing blood pressure and showed higher heart rates than
      patients anaesthetised with propofol and remifentanil, but there were no other
      haemodynamic differences between the groups in response to surgical stimuli.
      There were significantly shorter times to spontaneous ventilation (3.2 vs. 6.3
      min), extubation (3.8 vs. 9.5 min), eye opening (3.0 vs. 11.5 min) and giving
      name and date of birth (4.8 vs. 14.3 min) in patients anaesthetised with
      remifentanil and propofol than in those receiving desflurane and nitrous oxide.
      In addition, patients anaesthetised with remifentanil and propofol had a greater
      incidence of postoperative shivering. There were no significant differences
      between the two groups in the patients' pain scores, analgesic demand and
      incidence of nausea and vomiting. CONCLUSION: Patients anaesthetised with
      propofol and remifentanil have significantly shorter emergence times than
      patients anaesthetised with desflurane and nitrous oxide. The low incidence of
      postoperative pain after microsurgical vertebral disc resections requires no
      large-scale analgesic therapy, even after total intravenous anaesthesia including
      remifentanil.

PMID- 9530460
TI  - [Early clinical results with transnasal esophageal echocardiography].
AB  - Currently undergoing a clinical trial a new miniaturized monoplane ultrasound
      probe potentially enhances the practicability of perioperative transesophageal
      echocardiography (TEE) without loss of echocardiographic quality. METHODS: In the
      present prospective study, the nasally inserted miniaturized TEE probe was tested
      in 12 ventilated patients and compared with a conventional TEE probe.
      Echocardiographic quality was tested by two independent investigators by
      analyzing the percentage of the endocardium contour detection (< 50%, 50-75%, 75
      100%) in the left ventricular short- and long-axis views. RESULTS: In 11
      patients, more than 50% of endocardium were visualized continuously with both
      probes. Although the nasal TEE probe was inferior to conventional TEE in
      detecting lateral endocardium, automated endocardium detection compared well with
      both methods. Inter- and intraobserver variability in manual measurements of the
      left ventricular cross-sectional area was below 5% on average and differed non
      significantly with regard to the method. In 2 patients, continuous monitoring was
      aggravated by repeated loss of contact between the miniaturized TEE probe and
      mucosa. CONCLUSIONS: In comparison with conventional TEE, the miniaturized TEE
      probe provides practicability advantages without significant loss of information
      for cardiovascular monitoring.

PMID- 9530461
TI  - [Bovine hemoglobin. HBOC-201 causes a reduction of the oxygen partial pressure in
      poststenotic skeletal muscle].
AB  - We investigated the effects of ultrapurified polymerized bovine hemoglobin (HBOC
      201) on skeletal muscle tissue oxygen tension when applied before establishment
      of a nearly complete arterial stenosis. METHODS: Twelve foxhounds were
      anaesthetized IV and mechanically ventilated with 30% oxygen in air. Catheters
      were inserted into the right femoral artery and vein for measurements of
      haemodynamic parameters and blood-gas sampling. Arterial blood flow of the left
      popliteal artery was measured by an electromagnetic flow probe. Skeletal muscle
      tissue oxygen tension (tpo2) was measured in the left gastrocnemic muscle using a
      stepwise-driven polarographic needle probe, creating histograms from 200 single
      tpO2 measurements. Following isovolaemic haemodilution with Ringer's solution to
      a target haematocrit of 20%, the animals were randomly assigned to receive either
      200 ml of predonated fresh blood (group 1) or 200 ml of HBOC-201 (MW 32,000
      500,000; Hb 13 +/- 1 g-dl-1, group 2). After a 15-min stabilization period, a 95%
      artificial stenosis of the left popliteal artery was established. While animals
      of group 1 received two applications of 200 ml 6% hetastarch (HES, 200,000; 0.5),
      animals of group 2 received 200 ml Ringer's solution 45 and 75 min after
      establishment of the arterial stenosis, respectively. Variables were measured at
      baseline, after haemodilution and application of the respective compound, and 30,
      60 and 90 min after establishment of the stenosis. RESULTS: Demographic data,
      muscle temperature and arterial blood gases did not differ between groups. With
      the exception of a higher mean pulmonary artery pressure in HBOC-201-treated
      animals, haemodynamics did not differ between groups. In both groups oxygen
      delivery and oxygen consumption of the muscle decreased in parallel to the
      decreasing blood flow during arterial stenosis. In contrast, oxygen extraction
      ratio increased after infusion of HBOC-201 and remained unchanged during stenosis
      (P < 0.05). In group 1, the tpO2 decreased during stenosis when compared to
      baseline (P < 0.001) and remained decreased after administration of HES. In
      contrast, administration of 200 ml of HBOC-201 before establishment of the
      arterial stenosis sustained the tpO2 values at nearly baseline levels during
      stenosis. Skeletal muscle tissue oxygen tension was higher after HBOC-201
      infusion during stenosis when compared to HES infusion (P < 0.001). CONCLUSION:
      These data suggest that haemoglobin solutions can reach poststenotic tissues. The
      increased oxygen extraction after application of HBOC-201 is associated with
      improved skeletal muscle oxygen tension during severe arterial stenosis.

PMID- 9530462
TI  - [Clinical studies on emergency medicine. An application oriented classification,
      its planning and realization].
AB  - Clinical studies are usually conceived of as controlled randomized trials, as
      retrospective patient statistics or as single case reports. However, such a
      classification is too narrow and overlooks many other forms of study designs.
      This review, therefore, offers a more encompassing and practical classification
      of clinical studies for the field of emergency medicine. Randomized controlled
      trials fulfill scientific criteria at the highest level (gold standard):
      comparison, repeatability, objective measurement. At the same time, randomized
      trials also have to comply with demanding ethical criteria and must be
      justifiable in the individual patient. Therefore, comparable uncertainty with
      regard to the superiority of the treatment options under investigation is a sine
      qua non. In addition to randomized trials, six other groups of clinical trials
      have the potential to solve scientific questions in emergency medicine:
      observational studies, decision analysis, meta analysis, public health care
      studies, case reports and descriptive summary statistics and studies on ethical
      problems. This variability in trial designs calls for a clinically oriented
      methodologist; the concept and institutionalization of theoretical surgery has
      been a response to this demand. All study types in this review are illustrated by
      examples in emergency medicine. Literature for advanced reading in particular
      trial methodologies can be found in the reference list. A checklist summarizes
      all elements for designing and conducting randomized trials in emergency
      medicine. All clinical trials striving for a high standard of quality--whether
      randomized or not--depend on the following prerequisites:professional
      organization, time effort, a supportive social environment and a scientific
      culture.

PMID- 9530463
TI  - [Prevention of catheter-related infections, The official American guidelines-
      from the Centers for Disease Control].
AB  - The official German guidelines for prevention of intravascular-device-associated
      infections were published by the Bundes-gesundheitsamt, now called the Robert
      Koch-Institut, 12 years ago. The recently published official "Guidelines for
      Prevention of Intravascular-Device Associated Infections" of the Centers for
      Disease Control and Prevention (CDC) are categorized according to scientific
      evidence. The American guidelines are very detailed and differ in some aspects
      from the official German guidelines. The purpose of the present paper is to
      inform the German-speaking anaesthesiologist about the official CDC guidelines
      and to provide an update on the prevention of intravascular-device-associated
      infections.

PMID- 9530464
TI  - [Assistance in dying. Some consequences of living wills for the attending
      physician].

PMID- 9530465
TI  - [Postoperative nausea and vomiting].

PMID- 9530466
TI  - [Medicine and the specialized media. The specialist journal as scientific and
      forum economic factor].

PMID- 9530467
TI  - [Cholinesterase determination].

PMID- 9530468
TI  - [Autologous blood donation or volume substitutes].

PMID- 9530469
TI  - [Working place anesthesia and intensive care medicine--today and tomorrow].

PMID- 9530470
TI  - [Bedside pulmonary blood flow measurement by partial CO2 rebreathing].

PMID- 9530471
TI  - [Flexible forms of respiration in anesthesia. Description of respiratory
      possibilities of the anesthesia ventilator OHMEDA 7900].

PMID- 9530472
TI  - [Minimal flow anesthesia and intraoperative gas monitoring].

PMID- 9530473
TI  - [Anesthesiology and intensive care medicine as covered by the medical care
      ordinance (as seen by medical insurance bodies)].

PMID- 9530474
TI  - [Cost management in anesthesia].

PMID- 9530476
TI  - [Data recording and data processing in anesthesia. Report on experience with
      Modulus CD].

PMID- 9530475
TI  - [Hygienic aspects in the use of infusion filters].

PMID- 9530477
TI  - [To our readers].

PMID- 9530478
TI  - [Volume replacement solutions--pharmacology and clinical use].
AB  - PHYSIOLOGY AND PATHOPHYSIOLOGY: Total body water represents 60% of body weight
      (BW), consisting of 40% BW intra- and 20% BW extracellular fluid. Extracellular
      fluid is divided into 16% BW interstitial fluid and 4% BW plasma volume (Fig. 1).
      The colloid oncotic pressure (COP) of the plasma proteins, which is about 25 mmHg
      (Fig. 2), is the main factor for the retention of intravascular volume and the
      prevention of interstitial edema. Within a defined range, oxygen transport
      capacity can be improved by normovolaemic haemodilution. Under strictly
      normovolaemic conditions ("controlled haemodilution"), the critical haemoglobin
      concentration for intensive care patients is about 10.0 g/dl, and 8-6 g/dl in
      patients with satisfactory compensatory mechanisms under stable clinical
      conditions. Larger blood volume deficits are replaced step by step with volume
      replacement solutions (crystalloids and synthetic colloids), packed red cells,
      fresh-frozen plasma, and platelets (Fig. 3). VOLUME REPLACEMENT WITH CRYSTALLOID
      AND COLLOID SOLUTIONS: Crystalloid solutions do not contain any macromolecules.
      Due to their lack of intrinsic COP, they spread rapidly over the intravascular
      and interstitial space. To achieve a comparable volume effect like colloid
      solutions, a fourfold infusion volume is necessary. Thus, crystalloids should be
      used in addition to colloid solutions to compensate the interstitial fluid
      deficit. Hyperosmotic-hyperoncotic solutions have not yet been established, and
      their benefit seems doubtful. Synthetic colloid solutions contain gelatin,
      dextran, or hydroxyethyl starch (HES) molecules. Due to their intrinsic COP,
      fluid is fixated in the intravascular space (Fig. 4). Solutions with high COP
      increase the intravascular volume due to resorption of interstitial fluid (plasma
      expanders). Pharmacological characterisation of synthetic colloids includes
      concentration [%], mean molecular weight [x1,000 Dalton] and degree and position
      of substitution (HES only). Main clinical features are the maximal volume effect
      and the duration of a 100% and a 50% volume effect (Fig. 5). For economic
      reasons, 5% albumin should not be used for volume replacement. The use of 20%
      albumin in intensive care patients is also limited and recommended only if a
      capillary leck is unlikely and the dose limits of synthetic colloids are reached.
      Gelatin is a polypeptide of bovine origin and achieves a shortlasting isovolaemic
      volume effect. When compared with dextran or HES, negative effects on haemostatis
      are less, and the renal function is not impaired. Thus, gelatin is first of all
      indicated in patients with limited volume demand, and secondly in situations with
      massive blood losses, when the dose limits of HES are reached. Dextran has no
      specific benefits. HES is a polysaccharide of maize or potato origin. By
      substitution of glucose molecules with hydroxyethyl groups, starch molecules are
      protected against fast amylase degradation. Metabolism depends on the degree and
      position of substitution and mean molecular weight. Smaller molecules are
      eliminated via the kidneys, but a certain amount of larger molecules is stored in
      the reticulo-endothelial system. HES is available in very different preparations
      (concentration 3-10%, mean molecular weight 70,000-450,000 Dalton, substitution
      50-70%). Special indications of 10% HES 200/0.5 are rapid hypervolaemic
      replacement of massive blood losses and increase of COP in intensive care
      patients without capillary leak. Synthetic colloids as well as albumin may lead
      to adverse reactions, which are generally very rare. In large-scala studies, no
      significant differences have been found with regard to incidence and severity.

PMID- 9530479
TI  - [Level concept of analgesic dosing in intensive care medicine with sufentanil].
AB  - OBJECTIVE: The efficacy of a 3-level regimen of analgesia and sedation was
      investigated in a clinical setting. Level 1 consisted of continuous
      administration of sufentanil, in level 2 continuous administration of midazolam
      and level 3 continuous administration of midazolam and clonidine was added
      according to patients' needs. METHODS: Sufentanil at 1 microgram/kg/h was given
      initially. Later it was adjusted to patients' requirements in accordance with the
      Ramsay score (group 1). Long-term intubated patients received in addition
      midazolam 0.05 mg/kg/h (group 2). If needed, clonidine 1 microgram/kg/h was added
      (group 3). Mean drug requirements were investigated during controlled ventilation
      and during assisted ventilation with spontaneous breathing > 25% of total minute
      ventilation. In group 1 arterial paCO2 was measured to estimate drug-induced
      respiratory depression. Values given are median and ranges. RESULTS: With the 3
      level-regimen of analgesia and sedation a Ramsay score of 2-3 was achieved in all
      intensive-care patients. In group 1 (n = 109; 36.7%) paCO2 values were similar at
      all times. Patients on controlled ventilation needed sufentanil 0.6 (0.075-2.5)
      microgram/kg/h, on assisted ventilation 0.4 (0.05-2.5) microgram/kg/h. Patients
      of group 2 (n = 113; 38.1%) had on controlled ventilation a higher requirement of
      sufentanil 1.2 (0.09-2.7) micrograms/kg/h, in addition Midazolam 0.05 (0.002
      0.56) mg/kg/h was given. On assisted ventilation with spontaneous breathing > 25%
      sufentanil 0.9 (0.05-2.6) microgram/kg/h plus midazolam 0.04 (0.002-0.38) mg/kg/h
      was sufficient. Group 3 (n = 75; 25.2%) had on controlled ventilation a higher
      requirement of sufentanil with 1.5 (0.09-4.0) micrograms/kg/h and midazolam 0.05
      (0.005-0.52) mg/kg/h, in addition clonidine 1.1 (0.12-2.88) micrograms/kg/h was
      given. On assisted ventilation with spontaneous breathing > 25% requirement of
      sufentanil with 1.1 (0.15-2.6) micrograms/kg/h and of midazolam with 0.05 (0.002
      0.22) mg/kg/h was slightly lower, whereas more clonidine was needed with 1.3
      (0.12-2.88) micrograms/kg/h. CONCLUSION: Continuous infusion of sufentanil only
      for analgesia and sedation is suitable for intensive-care patients with a short
      stay in the ICU. Respiratory depression during spontaneous breathing is not
      significant. The supplementary administration of midazolam and clonidine
      according to the presented regimen was shown to be of advantage for patients with
      a longer stay in ICU.

PMID- 9530480
TI  - [Laughing gas as the principle substance in assessing occupational exposure to
      inhalation anesthetics].
AB  - PURPOSE: In the Federal Republic of Germany limits for the chronic exposure to
      nitrous oxide and volatile anaesthetics have been prescribed by legislation.
      According to the technical rules for the handling of hazardous substances TRGS
      402 it is legal to measure a single substance in a mixture of hazards, unless the
      behaviour of all substances is known. Studies about corresponding concentrations
      of nitrous oxide and volatile anaesthetics in anaesthetic working areas have not
      yet been carried out. METHODS: During one working week each the concentrations of
      nitrous oxide, enflurane and desflurane were measured by infrared spectrometry in
      a working area equipped with air condition and in a non-ventilated operating
      theatre. Corresponding concentrations of nitrous oxide were measured from the
      same gas samples. RESULTS: Statistical calculations showed linear correlations of
      the enflurane and nitrous oxide concentrations in all anaesthetic areas. No
      linear regression was found between the desflurane and nitrous oxide
      concentrations. In the working area where desflurane anaesthesias were carried
      out, significantly higher concentrations of nitrous oxide were observed.
      Nevertheless the Chi2-test showed no significant differences in the distribution
      of categorised measurement values. DISCUSSION: Although it is not possible to
      calculate desflurane concentrations from the nitrous oxide concentrations,
      measurement of nitrous oxide as leading substance is a valid procedure to assess
      the exposure of the anaesthesiology workplace to nitrous oxide and volatile
      anaesthetics. Significant higher nitrous oxide concentrations during desflurane
      anaesthesia result from early extubation of patients expiring higher
      concentrations of nitrous oxide.

PMID- 9530481
TI  - [Pulse oximetry and capnography in intensive care transportation: combined use
      reduces transportation risks].
AB  - OBJECTIVE: Due to the growing number of diagnostic and therapeutical procedures
      intensive-care patients must be transported intra- and interhospitally more
      often. These transports are among the most critical events during intensive-care
      therapy, with a high incidence of potentially life-threatening mishaps [23]. The
      aim of this study was to evaluate the possible benefit of the combined
      application of pulse oximetry and capnometry for patient safety during transport.
      METHODS: In a prospective clinical study 48 mechanically ventilated patients were
      allocated at random in 2 main study groups, 24 patients were investigated during
      interhospital transportation with an ambulance car, the other 24 patients during
      intrahospital transports. They were classified according to APACHE II and TISS.
      Blood pressure, heart rate and arterial blood gases were measured at eleven
      selected times. Twelve randomly chosen patients out of each main study group were
      monitored additionally with pulse oximetry and capnometry. The results were
      compared using the Mann-Whitney-U test. P < or = 0.05 was considered significant.
      RESULTS: Thirty-four patients had a TISS more than 40. The mean APACHE II-Score
      was 14 +/- 5. The overall incidence of potentially life-threatening mishaps was
      9. Six out of these 9 occurred in the 24 patients with additional monitoring and
      were immediately detected by pulse oximetry or capnometry. CONCLUSIONS: The
      combination of pulse oximetry and capnometry offers the possibility to detect
      potentially life-threatening problems in ventilated patients during transport.
      This allows for early therapeutical consequences and may help to reduce the risk
      of transports.

PMID- 9530483
TI  - [Intensive care medicine between quality and cost].

PMID- 9530482
TI  - [The cardiac risk patient].

PMID- 9530484
TI  - Are scoring systems adequate indicators for quality and performance of the ICU?

PMID- 9530485
TI  - [Application of scoring systems for quality assurance and cost estimation in
      intensive care medicine].

PMID- 9530486
TI  - [Quality management and individual performance recording in intensive care using
      the Goettingen Information System for Intensive Care and Surgery (GISI)].

PMID- 9530487
TI  - Outcome and ethics in intensive care.

PMID- 9530488
TI  - [3rd Intensive Care Colloquium Dresden--kidney and intensive care-- intensive
      care nephrology--Dresden, 2-3 May 1997].

PMID- 9530489
TI  - Genetic and environmental influences on human behavioral differences.
AB  - Human behavioral genetic research aimed at characterizing the existence and
      nature of genetic and environmental influences on individual differences in
      cognitive ability, personality and interests, and psychopathology is reviewed.
      Twin and adoption studies indicate that most behavioral characteristics are
      heritable. Nonetheless, efforts to identify the genes influencing behavior have
      produced a limited number of confirmed linkages or associations. Behavioral
      genetic research also documents the importance of environmental factors, but
      contrary to the expectations of many behavioral scientists, the relevant
      environmental factors appear to be those that are not shared by reared together
      relatives. The observation of genotype-environment correlational processes and
      the hypothesized existence of genotype-environment interaction effects serve to
      distinguish behavioral traits from the medical and physiological phenotypes
      studied by human geneticists. Behavioral genetic research supports the
      heritability, not the genetic determination, of behavior.

PMID- 9530490
TI  - From biophysics to models of network function.
AB  - Neurons and synapses display a rich range of time-dependent processes. Which of
      these are critical to understanding specific integrative functions in the brain?
      Computational methods of various kinds are used to understand how systems of
      neurons interact to produce behavior. However, these models often assume that
      neuronal dynamics and synaptic strengths are fixed. This review presents some
      recent models that illustrate that short-term synaptic plasticity mechanisms such
      as facilitation and depression can have important implications for network
      function. Other features of synaptic transmission such as multi-component
      synaptic potentials, cotransmission, and neuromodulation with obvious potential
      computational implications are presented. These examples illustrate that synaptic
      strength and intrinsic properties in networks are continuously varying on
      numerous time scales as a function of the temporal patterns of activity in the
      network. Thus, both firing frequency of the neurons in a circuit, and the
      modulatory environment determine the intrinsic and synaptic properties that
      produce behavior.

PMID- 9530491
TI  - Local circuits in primary visual cortex of the macaque monkey.
AB  - The basic laminar organization of excitatory local circuitry in the primary
      visual cortex of the macaque monkey is similar to that described previously in
      the cat's visual cortex (Gilbert 1983). This circuitry is described here in the
      context of a two-level model that distinguishes between feedforward and feedback
      connections. Embedded within this basic framework is a more complex organization.
      Within the strictly feedforward pathway, these circuits distribute unique
      combinations of magno-, parvo-, and koniocellular input from the lateral
      geniculate nucleus (LGN) to neurons in layers 2-4B. Their input is dependent on
      the extrastriate cortical areas they target. The local feedback connections from
      deep layers (5 and 6) arise from a diverse population of pyramidal neurons. Each
      type forms local connections with a unique relationship to more superficial
      layers. In the case of layer 6 neurons, these connections are closely related to
      layer 4 subdivisions receiving input from different functional streams.

PMID- 9530492
TI  - RAB3 and synaptotagmin: the yin and yang of synaptic membrane fusion.
AB  - Synaptic vesicle exocytosis occurs in consecutive steps: docking, which
      specifically attaches vesicles to the active zone; priming, which makes the
      vesicles competent for Ca(2+)-triggered release and may involve a partial fusion
      reaction; and the final Ca(2+)-regulated step that completes fusion. Recent
      evidence suggests that the critical regulation of the last step in the reaction
      is mediated by two proteins with opposite actions: synaptotagmin, a Ca(2+)
      binding protein that is essential for Ca(2+)-triggered release and probably
      serves as the Ca(2+)-sensor in fusion, and rab3, which limits the number of
      vesicles that can be fused as a function of Ca2+ in order to allow a temporally
      limited, repeatable signal.

PMID- 9530493
TI  - Adhesion molecules and inherited diseases of the human nervous system.
AB  - Mutations in the human genes for the adhesion molecules Po, L1, and merosin cause
      severe abnormalities in nervous system development. Po and merosin are required
      for normal myelination in the nervous system, and L1 is essential for development
      of major axon pathways such as the corticospinal tract and corpus callosum. While
      mutations that lead to a loss of the adhesive function of these molecules produce
      severe phenotypes, mutations that disrupt intracellular signals or intracellular
      interactions are also deleterious. Geneticists have found that more than one
      clinical syndrome can be caused by mutations in each of these adhesion molecules,
      confirming that these proteins are multifunctional. This review focuses on
      identifying common mechanisms by which mutations in adhesion molecules alter
      neural development.

PMID- 9530494
TI  - CREB and memory.
AB  - The cAMP responsive element binding protein (CREB) is a nuclear protein that
      modulates the transcription of genes with cAMP responsive elements in their
      promoters. Increases in the concentration of either calcium or cAMP can trigger
      the phosphorylation and activation of CREB. This transcription factor is a
      component of intracellular signaling events that regulate a wide range of
      biological functions, from spermatogenesis to circadian rhythms and memory. Here
      we review the key features of CREB-dependent transcription, as well as the
      involvement of CREB in memory formation. Evidence from Aplysia, Drosophila, mice,
      and rats shows that CREB-dependent transcription is required for the cellular
      events underlying long-term but not short-term memory. While the work in Aplysia
      and Drosophila only involved CREB function in very simple forms of conditioning,
      genetic and pharmacological studies in mice and rats demonstrate that CREB is
      required for a variety of complex forms of memory, including spatial and social
      learning, thus indicating that CREB may be a universal modulator of processes
      required for memory formation.

PMID- 9530495
TI  - Cortical plasticity: from synapses to maps.
AB  - It has been clear for almost two decades that cortical representations in adult
      animals are not fixed entities, but rather, are dynamic and are continuously
      modified by experience. The cortex can preferentially allocate area to represent
      the particular peripheral input sources that are proportionally most used.
      Alterations in cortical representations appear to underlie learning tasks
      dependent on the use of the behaviorally important peripheral inputs that they
      represent. The rules governing this cortical representational plasticity
      following manipulations of inputs, including learning, are increasingly well
      understood. In parallel with developments in the field of cortical map
      plasticity, studies of synaptic plasticity have characterized specific elementary
      forms of plasticity, including associative long-term potentiation and long-term
      depression of excitatory postsynaptic potentials. Investigators have made many
      important strides toward understanding the molecular underpinnings of these
      fundamental plasticity processes and toward defining the learning rules that
      govern their induction. The fields of cortical synaptic plasticity and cortical
      map plasticity have been implicitly linked by the hypothesis that synaptic
      plasticity underlies cortical map reorganization. Recent experimental and
      theoretical work has provided increasingly stronger support for this hypothesis.
      The goal of the current paper is to review the fields of both synaptic and
      cortical map plasticity with an emphasis on the work that attempts to unite both
      fields. A second objective is to highlight the gaps in our understanding of
      synaptic and cellular mechanisms underlying cortical representational plasticity.

PMID- 9530496
TI  - Human autoimmune neuropathies.
AB  - Peripheral nerve diseases are among the most prevalent disorders of the nervous
      system. Because of the accessibility of the peripheral nervous system (PNS) to
      direct physiological and pathological study, neuropathies have traditionally
      played a unique role in developing our understanding of basic mechanism of
      nervous system injury and repair. At present they are providing new insight into
      the mechanisms of immune injury to the nervous system. A rapidly growing
      catalogue of PNS disorders are now suspected to be immune-mediated, and in the
      best understood of these disorders, the molecular and cellular targets of immune
      attack are known, and the pathophysiology follows directly from the specific
      immune injury. This review summarizes the immunologically relevant features of
      the PNS, then considers selected immune-mediated neuropathies, focusing on
      pathogenetic mechanisms. Finally, the PNS is providing a testing ground for new
      immunotherapies and approaches to protection and regeneration, including the use
      of trophic factors. The current status of treatment and implications for future
      approaches is reviewed.

PMID- 9530497
TI  - Sense and the single neuron: probing the physiology of perception.
AB  - The newly defined field of cognitive neuroscience attempts to draw together the
      study of all brain mechanisms that underlie our mental life. Historically, the
      major sensory pathways have provided the most trustworthy insights into how the
      brain supports cognitive functions such as perception, attention, and short-term
      memory. The links between neural activity and perception, in particular, have
      been studied revealingly in recent decades. Here we review the striking progress
      in this area, giving particular emphasis to the kinds of neural events that
      underlie the perceptual judgments of conscious observers.

PMID- 9530498
TI  - Signal transduction in the Caenorhabditis elegans nervous system.
AB  - Caenorhabditis elegans interacts with its environment by sensing chemicals,
      touch, and temperature; genetic analysis of each of these responses has led to
      the identification of candidate signaling molecules within sensory neurons. A
      molecular model for touch sensation has emerged from studies of the
      mechanosensory response; the receptors and signal transduction mechanisms in
      olfactory neurons are being elucidated; and an unusual neuroendocrine role for a
      TGF-beta-related peptide in chemosensory neurons has been discovered. Presynaptic
      and postsynaptic components of neuronal synapses have been identified in
      behavioral and pharmacological mutant screens. Mutations have been found in
      multiple classes of nicotinic acetylcholine receptor genes, excitatory and
      inhibitory glutamate receptor genes, and candidate gap junction genes, allowing
      their function to be studied in vivo. Different G-protein signaling pathways have
      characteristic effects on behavior, neuronal degeneration, and embryonic
      development.

PMID- 9530499
TI  - The ephrins and Eph receptors in neural development.
AB  - The Eph receptors are the largest known family of receptor tyrosine kinases.
      Initially all of them were identified as orphan receptors without known ligands,
      and their specific functions were not well understood. During the past few years,
      a corresponding family of ligands has been identified, called the ephrins, and
      specific functions have now been identified in neural development. The ephrins
      and Eph receptors are implicated as positional labels that may guide the
      development of neural topographic maps. They have also been implicated in pathway
      selection by axons, the guidance of cell migration, and the establishment of
      regional pattern in the nervous system. The ligands are anchored to cell
      surfaces, and most of the functions so far identified can be interpreted as
      precise guidance of cell or axon movement. This large family of ligands and
      receptors may make a major contribution to the accurate spatial patterning of
      connections and cell position in the nervous system.

PMID- 9530500
TI  - Zinc and brain injury.
AB  - Zinc is an essential catalytic or structural element of many proteins, and a
      signaling messenger that is released by neural activity at many central
      excitatory synapses. Growing evidence suggests that zinc may also be a key
      mediator and modulator of the neuronal death associated with transient global
      ischemia and sustained seizures, as well as perhaps other neurological disease
      states. Manipulations aimed at reducing extracellular zinc accumulation, or
      cellular vulnerability to toxic zinc exposure, may provide a novel therapeutic
      approach toward ameliorating pathological neuronal death in these settings.

PMID- 9530501
TI  - Inducible gene expression in the nervous system of transgenic mice.
AB  - Gene function during mammalian development is often studied by making
      irreversible changes to the genome. This approach has a major drawback in that
      the function of the gene in question must be deduced from the phenotype of
      animals that have been deficient for the product of the disrupted gene throughout
      ontogeny. Compensation for the loss of the gene product could yield an apparently
      unaltered phenotype. Alternatively, the changes in the regulation of other genes
      could yield a misleading phenotype. If the genetic manipulation results in
      embryonic or neonatal lethality, gene function at later stages of development
      cannot be analyzed. It would thus be highly advantageous if the expression of a
      particular gene could be restricted both temporally and spatially through the use
      of an inducible genetic system. This paper describes the various inducible
      genetic expression systems developed for use in mammalian cells, with particular
      emphasis on their application in the nervous system of transgenic mice.

PMID- 9530502
TI  - Gene discovery in Drosophila: new insights for learning and memory.
AB  - Genetic approaches have been used to investigate increasingly complex biological
      systems. Here we review the current state of genetic analysis of learning and
      memory in the fruitfly, Drosophila melanogaster. Emerging findings support two
      main themes. First, discovery and manipulation of genes involved with behavioral
      plasticity in genetically accessible systems such as D. melanogaster enables
      dissection of the biochemical, cellular, anatomical, and behavioral pathways of
      learning and memory. Second, because core cellular mechanisms of simple forms of
      learning are evolutionarily conserved, biological pathways discovered in
      invertebrates are likely to be conserved in vertebrate systems as well.

PMID- 9530503
TI  - Regionalization of the prosencephalic neural plate.
AB  - Recent embryological studies are beginning to establish that the underlying
      organization of the forebrain may be reduced to relatively simple elements that
      are common to all vertebrates. We begin this chapter by reviewing studies that
      describe the similarities in prospective fate and molecular organization of the
      developing neural plate in fish, frogs, chickens, and mice. The chapter next
      addresses mechanisms that regulate regional specification in the anterior central
      nervous system. There is now evidence that the axial mesendoderm anterior to the
      notochord (the prechordal plate) has a central role in induction of the floor and
      basal plate primordia (hypothalamus) of the forebrain. Patterning of the
      anterolateral neural plate (telencephalon) may be regulated by FGF8 produced in
      the anterior neural ridge. Thus, the synthesis of information from fate mapping
      and experimental embryological and genetic studies is illuminating the mechanisms
      that generate the different components of the forebrain.

PMID- 9530504
TI  - Mutant genes in familial Alzheimer's disease and transgenic models.
AB  - The most common cause of dementia occurring in mid- to late-life is Alzheimer's
      disease (AD). Some cases of AD, particularly those of early onset, are familial
      and inherited as autosomal dominant disorders linked to the presence of mutant
      genes that encode the amyloid precursor protein (APP) or the presenilins (PS1 or
      PS2). These mutant gene products cause dysfunction/death of vulnerable
      populations of nerve cells important in memory, higher cognitive processes, and
      behavior. AD affects 7-10% of individuals > 65 years of age and perhaps 40% of
      individuals > 80 years of age. For the late-onset cases, the principal risk
      factors are age and apolipoprotein (apoE) allele type, with apoE4 allele being a
      susceptibility factor. In this review, we briefly discuss the clinical syndrome
      of AD and the neurobiology/neuropathology of the disease and then focus attention
      on mutant genes linked to autosomal dominant familial AD (FAD), the biology of
      the proteins encoded by these genes, and the recent exciting progress in
      investigations of genetically engineered animal models that express these mutant
      genes and develop some features of AD.

PMID- 9530505
TI  - Inductions of immediate early genes (IEGS) and ref-1 by human chorionic
      gonadotropin in murine Leydig cell line (MA-10).
AB  - The effect of human chorionic gonadotropin (hCG) on the expression of immediate
      early genes (IEGs) including all members of fos and jun family, and c-myc was
      studied using mouse Leydig cell line (MA-10 cells) by Northern blot analyses. In
      addition, the induction of ref-1 which enhances DNA binding of fos/jun proteins
      was also analyzed. HCG induced a rapid and transient expression of c-fos, fosB, c
      jun, junB, junD and c-myc with a peak at 30 min to 1 h. In contrast, induction of
      fra-1 mRNA was delayed with a peak at 3 hr. However, fra-2 mRNA was immediately
      increased by hCG with a peak at 1 h. The ref-1 mRNA was expressed before the
      stimulation and its level was not altered by hCG at least for 8 hr. The
      differential induction of IEGs and continuous expression of ref-1 mRNA suggest an
      important role of their gene products on the regulation of Leydig cell function
      by hCG.

PMID- 9530506
TI  - Increment of efficiency in the identification of noble genes by colony
      hybridization assay. (Screening of low redundant clones from human fetal cDNA
      library).
AB  - For the rapid identification of noble genes in a specific tissue by computer
      analysis from the cDNA sequences determined by single-pass cDNA sequencing, clone
      redundancy was one of the major obstacles. To facilitate the efficiency in
      identification of noble genes, it was necessary to reduce the number of clones to
      be sequenced by eliminating the redundant clones for a rapid analysis. In order
      to increase the probability of isolating noble sequences from the cDNA clones of
      human fetal liver tissue origin, colony hybridization assay was adopted and
      redundant clones were efficiently removed. Four cDNA clones highly redundant in
      the human fetal liver cDNA libraries including alpha-globin, gamma-globin, serum
      albumin and H19 RNA sequences were selected as the probes. Two hundreds and sixty
      two cDNA clones were randomly selected and tested with the probes for
      hybridization properties. The identity of each cDNA clone giving positive or
      negative signals in the hybridization assay was determined by DNA homology search
      with the nucleic acid databases. Among the 76 clones giving positive signals, 57
      clones (75%) were found to be identical to the probe sequences and could be
      eliminated by colony hybridization assay before neucleotide sequencing.

PMID- 9530507
TI  - Group specific antibodies against the putative AMP-binding domain signature
      SGTTGXPKG in peptide synthetases and related enzymes.
AB  - The superfamily of adenylate forming enzymes including peptide synthetases, acyl
      CoA synthetases and insect luciferases is readily identified by the signature
      sequence SGTTGXPKG. This sequence including an invariant lysyl residue is located
      in a disordered loop region and was predicted to be of significant antigenicity.
      Antibodies were generated employing YTSGTTGRPKGC attached to bovine serum albumin
      and have been successfully used to identify respective enzymes and adenylate
      forming domains in multienzyme systems. These include the delta-(L-alpha
      aminoadipyl)-L-cysteinyl-D-valine synthetases of Aspergillus nidulans and
      Acremonium chrysogenum, gramicidin S synthetase 1 and tyrocidine synthetase 1
      from Bacillus brevis, acetyl-CoA synthetase from Alcaligenes eutrophus and a
      putative peptide synthetase from Metarhizium anisopliae. Weaker or no reactions
      are observed when the amino acid in position X in the protein is non-basic or
      hydrophobic, which is respectively the case for gramicidin S synthetase 1 and
      luciferase.

PMID- 9530508
TI  - Effects of ultraviolet-B radiation on phycobilisomes of Synechococcus PCC 7942:
      alterations in conformation and energy transfer characteristics.
AB  - Phycobilisomes (PBS), the major light harvesting antenna of the cyanobacterium
      Synechococcus contain phycocyanin (PC) and allophycocyanin (APC) as major pigment
      protein complexes. PBS also absorb ultraviolet-B (280-320 nm) radiation. Exposure
      of Synechococcus PBS to low dose of UV-B (approximately 0.28 mw.cm-2) for 90 min
      induced change in absorption, emission and excitation characteristics of PBS and
      these changes got enhanced after 3 h of exposure. Room temperature excitation and
      emission spectra clearly indicated uncoupling of energy transfer from PC to APC
      on exposure to UV-B. Also, the 77K emission spectra suggested that F682 emission
      originating from APC decreased by 42% after 3 h of exposure. Circular dichroism
      (CD) spectra of UV-B exposed PBS indicated changes (14% decrease) in the alpha
      helical content after 90 min treatment. SDS-PAGE analysis indicated degradation
      of a 75 kDa polypeptide (which appear to be a linker polypeptide) on UV-B
      treatment. The degradation of this polypeptide seems to induce changes in pigment
      protein interaction and decoupling of energy transfer within the PBS. Our results
      for the first time clearly indicate that the PBS of Synechococcus are targets for
      UV-B damage.

PMID- 9530509
TI  - Protein kinase C from rainbow trout brain: identification and characterization of
      three isozymes.
AB  - Free and membrane-associated fractions of protein kinase C (PKC) from rainbow
      trout (Onchorynchus mykiss) brain tissue were separated by hydroxylapatite
      chromatography and characterized kinetically. In both resting fish and in fish
      swum to exhaustion, approximately 40% of the total PKC activity was bound to
      membranes. Quantification of the three distinct hydroxylapatite chromatography
      peaks (PKC types gamma, beta and alpha) in cytosolic and membrane fractions
      revealed different isozyme distributions. The cytosolic fraction contained 21%
      PKC type gamma, 52% PKC type beta and 27% PKC type alpha. The membrane-associated
      fraction contained 23% PKC type gamma, 28% PKC type beta and 49% PKC type alpha.
      Kinetic characterization of the three isozymes showed that PKC type gamma was
      almost completely activated by Ca2+ alone whereas PKC type beta and PKC type
      alpha were 40% and 60% activated by Ca2+. Full activity for all enzymes was
      observed only in the presence of phosphatidylserine and diacylglycerol.
      Differences in the kinetic constants for the three isozymes were also apparent.
      PKC type gamma had a much lower affinity for Histone III-S when compared with PKC
      types beta and alpha (100 micrograms/ml as compared with 1.7 and 5.7
      micrograms/ml). PKC type gamma also had a lower affinity for calcium (0.22
      microM) when compared with PKC type beta (0.08 microM) and PKC type alpha (0.05
      microM). PKC type alpha had a lower affinity for phosphatidylserine (8.6
      micrograms/ml) when compared with PKC type gamma (0.37 microgram/ml) and PKC type
      beta (0.89 microgram/ml).

PMID- 9530510
TI  - An archaeal DNA binding protein from thermophilic Sulfolobus acidocaldarius forms
      different types of complexes with DNA.
AB  - We have characterized a DNA binding protein (DBNP-B) from the thermoacidophilic
      archaeon Sulfolobus acidocaldarius with respect to its interaction with single
      and double stranded DNA. The protein in solution exists predominantly as dimer as
      indicated by cross linking studies. Binding of DBNP-B to etheno DNA and poly (dA)
      resulted in fluorescence enhancement and hyperchromicity respectively. Ethidium
      bromide intercalated into DNA was completely displaced by DBNP-B. DNase I
      digestion of dsDNA was increased at subsaturating concentration of the protein
      and was inhibited at higher concentrations. These results and electron microscopy
      indicate that the protein forms different types of novel complexes with DNA at
      different protein to DNA ratios.

PMID- 9530511
TI  - Cloning and expression of a Clostridium thermocellum xylanase gene in Escherichia
      coli.
AB  - A Clostridium thermocellum xylanase gene, designated xynX, was cloned in
      Escherichia coli and was categorized a novel gene as a result of the comparison
      of restriction patterns of the C. thermocellum xylanase genes so far reported.
      The xynX gene encodes a xylanase having the molecular weight of 105 kilodaltons.
      A number of smaller truncated proteins with activities towards 4
      methylumbelliferyl-beta-D-cellobioside and xylan were also produced. The enzyme
      hydrolyzed xylan to xylo-oligosaccharide, indicating typical activity of endo
      beta-1,4-xylanase. This endoxylanase hydrolyzed carboxymethylcellulose without
      notable reduction of the viscosity as an exo-beta-1,4-glucanase, even though the
      enzyme exhibited very low levels of activity against other soluble and insoluble
      cellulosic substrates.

PMID- 9530512
TI  - Epitope analysis of monoclonal antibodies to human Gc globulin (vitamin D-binding
      protein).
AB  - Gc globulin, also called vitamin D-binding protein, is a human 56 kDa plasma
      protein. Antigenic epitopes of the protein recognized by 12 different monoclonal
      antibodies (MoAbs), including the previously prepared MoAb E12 of which binding
      to Gc is inhibited by actin, were analyzed in relation to the functional domains
      of the protein. To map the epitopes recognized by the respective antibody, the
      reactivities of the MoAbs were tested by immunoblotting against the recombinant
      Gc fragments expressed in E. coli cells, and then a competitive ELISA was
      performed. The results showed that the antibodies were classified into at least
      six groups. Furthermore, in addition to E12, actin inhibited the reactivity of
      MoAb 21, of which the epitope was located within residues Asp320 to Glu379, in an
      ELISA in the presence of the ligand. This result must indicate that this antibody
      binding site is near the site that interacts with actin. In contrast, no
      inhibitory effect by 25-hydroxyvitamin D to any antibodies was observed.
      Furthermore, all antibodies, including E12 and 21, reacted with membrane-bound Gc
      of lymphocytes by an immunofluorescence study, suggesting that Gc is unlikely to
      bind to the plasma membrane in its interaction with actin.

PMID- 9530513
TI  - Electrostatic inhibition of hemolysis induced by organotin compounds.
AB  - The effect of cations on the kinetics of hemolysis caused by organotin compounds
      was studied. The ions used in the investigation diminish or totally inhibit
      hemolysis of red cells induced by organotin compounds. The degree of inhibition
      depends both on the kind of ion and the compounds that induce hemolysis. The ions
      Zn2+, Co2+, and Cd2+ present in the medium at 50 microM concentration totally
      protect the erythrocytes against hemolysis induced by the compound (C3H7)3SnCl.
      The study has also shown the monovalent ions K+ and trimethyldodecylammonium
      bromide are less potent inhibitors of hemolysis than divalent ions, which is not
      the case for two non-ionic organotin compounds only. The studies performed
      indicate that hemolysis induced by organotin compounds is inhibited due to
      electrostatic interaction between the cations selected and erythrocyte membrane.

PMID- 9530514
TI  - Transition protein 1 from boar late spermatid nuclei having DNA-melting activity
      is a dimeric protein.
AB  - Polyacrylamide gel electrophoretic behavior of boar transition protein 1, TP1,
      under dissociating and non-dissociating buffer conditions, and titration of
      fluorescently labeled TP1 with increasing amounts of TP1 showed that TP1 formed a
      dimer without intermolecular disulfide bond. TP1 dimer with intermolecular
      disulfide bond had similar DNA-melting activity to TP1, but was not detected in
      extracts from boar late spermatid nuclei. These results suggest that TP1 dimer
      without intermolecular disulfide bond induces local destabilization of DNA in the
      late spermatid nuclei.

PMID- 9530515
TI  - Isolation and characterization of 5'-regulatory region of mouse activin beta A
      subunit gene.
AB  - We isolated genomic clones that contain the 5'-flanking region of the mouse
      activin beta A subunit gene. The nucleotide sequence determination of the 5'
      flanking region of the gene and the comparison of that with the reported mouse
      cDNA structure identified the putative 5' regulatory region, a novel first exon
      and a part of the first intron of the gene within this region. The putative 5'
      regulatory region of the mouse activin beta A subunit gene directed the
      expression of CAT gene in transfected HT1080 cells. Successive deletions of this
      region demonstrated a 400-bp region that exerts a strong positive effect on
      promoter activity of the mouse activin beta A subunit gene.

PMID- 9530517
TI  - Transfer of cholesterol from macrophages to lymphocytes in culture.
AB  - A major feature of macrophage metabolism is its capacity to produce and export
      cholesterol. Several reports have shown that the manipulation of lymphocyte
      cholesterol content elicits important changes in lymphocyte proliferation. These
      findings lead to an inquiry as to whether macrophage-derived cholesterol released
      into the lymphocyte surroundings may be transferred to the latter thus affecting
      lymphocyte function. In this study, cholesterol transfer from macrophages to
      lymphocytes was examined in vitro using rat cells in culture. The findings
      indicate that there may be a significant transfer of cholesterol from [4
      14C]cholesterol labeled resident peritoneal macrophages to mesenteric lymph node
      resting lymphocytes (up to 173.9 +/- 2.7 pmol/10(7) lymphocytes/10(7) macrophages
      when co-cultivated for 48 h), in a lipoprotein-dependent manner. This represents
      the mass transfer of ca. 17 nmoles of cholesterol molecules per 10(7) lymphocytes
      from 10(7) macrophages (calculated on the basis of specific radioactivity
      incorporated into macrophages after the pre-labelling period), which suggests
      that macrophages are capable of replacing the whole lymphocyte cholesterol pool
      every 21 h. Moreover, an 111%-increase in the total cholesterol content of
      lymphocytes was found after co-cultivation with macrophages for 48 h. When
      compared to peritoneal cells, monocytes/macrophages obtained from circulating
      blood leukocytes presented a much higher cholesterol transfer capacity to
      lymphocytes (3.06 +/- 0.10 nmol/10(7) lymphocytes/10(7) macrophages co-cultivated
      for 24 h). Interestingly, inflammatory macrophages dramatically reduced their
      cholesterol transfer ability (by up to 91%, as compared to resident macrophages).
      Cholesterol transfer may involve a humoral influence, since it is not only
      observed when cells are co-cultivated in a single-well chamber system (cells in
      direct contact), but also in a two-compartment system (where cells can
      communicate but not by direct contact). Co-cultivation with macrophages decreased
      the basal incorporation of [2-14C]thymidine into lymphocyte DNA and the addition
      of cholesterol to lymphocyte culture media also impaired the lymphocyte
      proliferative response to the mitogens concanavalin A (Con A) and bacterial
      lipopolysaccharide (LPS). The above results suggest that macrophages may transfer
      cholesterol to lymphocytes (from both lymph nodes and blood), thus regulating
      lymphocyte function by raising the intracellular cholesterol content and
      suppressing lymphocyte proliferative activity. If this is so, a modulatory role
      for the transfer of cholesterol in both physiological (e.g. immune response) and
      pathological conditions (e.g. atherosclerosis) may be postulated. This hypothesis
      is currently under investigation in our laboratory.

PMID- 9530516
TI  - Involvement of a third histidine in the ferrous active site of isopenicillin N
      synthase of Cephalosporium acremonium repudiated by recombinant double histidine
      mutants.
AB  - Site-directed mutagenesis studies have shown that the isopenicillin N synthase of
      Cephalosporium acremonium (cIPNS) requires two essential histidine residues
      (H216, H272) for activity. The determination of iron bound to the wildtype cIPNS
      and its absence in the mutants lacking histidine at positions 216 and 272 clearly
      supports the essential role these two histidines play in iron binding. However,
      nuclear magnetic resonance (NMR) studies have indicated that there could be three
      histidine residues that possibly coordinate the essential iron at the active
      site. To search for a presumed third histidine ligand, mutant cIPNS genes
      containing mutations at two histidine codons were created by in vitro cloning of
      fragments from the expression vectors bearing the respective cIPNS genes each
      with a single histidine mutation at positions H49, H64, H116, H126 and H137. All
      ten possible double histidine mutant cIPNS constructs were subsequently expressed
      in Escherichia coli. If a third histidine had a participatory role in the iron
      active centre of cIPNS, then one of the constructed double histidine mutants
      would have lost its enzymatic activity. However, analysis of the cIPNS activities
      of these recombinant double histidine mutants indicated that none of them was
      totally inactivated. Thus, the involvement of a third histidine can be
      repudiated.

PMID- 9530518
TI  - Isolation of thermostable phosphatase from the hyperthermophilic archaeon
      Thermococcus pacificus by immobilized metal affinity chromatography.
AB  - Phosphatase was isolated from cells of the hyperthermophilic marine archaeon
      Thermococcus pacificus by a procedure including chromatography on Butyl-Fractogel
      TSK-650 and Ni(2+)-iminodiacetic-agarose. Enzyme activity is maximal at 90
      degrees C, and the enzyme half-life time at this temperature is 1 h. The pH
      optimum of phosphatase activity is 6.0. Electrophoresis under denaturating
      conditions yielded a subunit molecular weight of 45 kDa. On gel-filtration on
      Sephacryl S-300 HR three peak corresponding to 295, 85 and 45 kDa were observed,
      suggesting that the enzyme is a homohexamer.

PMID- 9530519
TI  - Univalent cation fluxes in yeast.
AB  - Transport of H+, K+, Rb+ and Tl+ ions was studied in a wild-type strain of
      Saccharomyces cerevisiae and in its mutants defective in the high-affinity K+
      transport system TRK1 and in the double mutant with an additional deletion in the
      TRK2 gene. In the absence of glucose K+, Rb+ and Tl+ elicited a more or less
      stoichiometric exchange outflow of H+, in the mutants K+ moved out of cells even
      in the presence of 10 mM KCl or KNO3. In the presence of glucose in the wild
      type, K+, Rb+ and Tl+ brought about a massive outflow of H+ while being
      transported inward against high concentration gradients. In the trk1 delta mutant
      the exchange fluxes were reduced by 65-85%, in the double mutant those of K+, Rb+
      and Tl+ practically cease but outflow of H+ caused by Tl+ remained at the level
      of the trk1 delta mutant. It appears that, in addition to the H+ export by the
      PMA1-coded plasma membrane H(+)-ATPase, at least three different univalent-cation
      involving activities are present: the high-affinity transport system for K+
      (TRK1), another system (possibly TRK2) with different responses to K+ and Rb+,
      vs. Tl+, and an active system for K+ export. The first two are apparently active
      exchange systems for K+, Rb+, and Tl+ against H+. The source of energy for these
      highly active transports (acting against gradients of 1000:1 and 5000:1,
      respectively) is unclear.

PMID- 9530520
TI  - Induction of buccal mucosal apoptosis with chronic alcohol ingestion.
AB  - In this study we investigated buccal mucosal cells apoptosis and the expression
      of regulatory cytokines, tumor necrosis factor-alpha (TNF-alpha) and interleukin
      4(IL-4) with chronic ethanol ingestion. The buccal mucosa of rats maintained for
      23 days on alcohol-containing and control liquid diet was assessed for IL-4 and
      TNF-alpha content, and the extent of epithelial cells apoptosis. While the
      expression of TNF-alpha in alcohol diet group showed a significant increase (1.9
      fold) over that of the controls, less apparent differences between the two groups
      were observed in the content of IL-4 (141.8 +/- 28.2 vs. 119.8 +/- 7.3 pg/mg
      protein). The DNA fragmentation assays revealed that alcohol diet group also
      exhibited a 3.5-fold enhancement in buccal mucosal cells apoptosis. Moreover, the
      apoptotic index showed positive correlation (r = 0.53) with the extent of induced
      changes in TNF-alpha. These results demonstrate that ethanol-induced buccal
      mucosal cells apoptosis is triggered by the enhancement in TNF-alpha expression.

PMID- 9530521
TI  - Studies on the heterologous expression of BstVI restriction endonuclease in
      Escherichia coli.
AB  - Bacterial restriction and modification systems must be regulated to avoid self
      restriction. It is generally accepted that cognate DNA methyltransferases
      normally protects both, the host's chromosome and extrachromosomal elements from
      the activity of their endonuclease counterparts. When the bstVIRM genes from
      Bacillus stearothermophilus V were subcloned into Escherichia coli, several
      clones exhibiting a r+m- phenotype were originated. The present work was
      undertaken to analyze the possibility that mechanisms other than DNA methylation
      could account for the viability of these cells. No evidence was found for an
      inhibitory agent or endonuclease compartmentation. In vivo experiments showed
      that lambda phage multiplication was poorly restricted by the heterologous
      enzyme. The restricting activity against the incoming phase increased however
      when phage adsortion was performed at higher temperatures. Analogous experiments
      in which a DNA-repair deficient strain was used as a host for the thermophilic R
      M system suggested, to some extent, the participation of the repair machinery in
      the viability of r+m- clones.

PMID- 9530522
TI  - Mapping of quantitative trait loci for body weight on chromosomes 1 and 4 in the
      rat.
AB  - Quantitative trait loci (QTLs) affecting body weight were investigated in the
      backcross population derived from diabetic BB/OK and spontaneously hypertensive
      rat (SHR). The F1 hybrids were backcrossed onto BB/OK rats, and QTL analysis was
      performed with the resulting backcross population on chromosomes 1, 3, 4, 10, 13
      and 18. According to the stringent threshold for a lod score of 3.0, markers on
      chromosomes 1 and 4 were found to be linked with body weight. The QTL with a peak
      lod score (3.3) on chromosome 1 for a male population was located within the
      region flanked by loci Igf2 and D1Mgh12. On chromosome 4, linkage between the
      body weight and the region around the Npy locus was observed (lod score 3.1). The
      existence of the QTL on chromosome 4 affecting body weight was confirmed by
      congenic BB.LL rats, carrying chromosomal region of SHR (D4Mit6-Npy-Spr) on the
      genetic background of the BB/OK rat.

PMID- 9530523
TI  - A novel p53 mutation hotspot at codon 132 (AAG-->AGG) in human renal cancer.
AB  - Mutations of p53 tumor suppressor gene are the most common genetic alterations in
      a variety of human carcinomas. The sites of p53 mutations, however, vary in
      different cancers. The present study was designed to characterize p53 mutations
      in 40 primary human renal cancer specimens using hot-start-PCR-single-strand
      conformation polymorphism (SSCP) analysis, sequencing of PCR product and
      immunohistochemistry. DNA extracted from microdissected paraffin-embedded
      sections was amplified by hot-start-PCR using oligonucleotide primers specific
      for exons 4-9 of p53. The mutations were analyzed by PCR-SSCP technique and the
      generated fragments were denatured and analyzed by 6% polyacrylamide gel
      electrophoresis. The samples showing a band shift were denatured and sequenced
      using the Sequenase Version 2.0 DNA Sequencing Kit (US Biochemical, Cleveland,
      Ohio). Genomic DNA from control samples containing wild-type p53 alleles was
      sequenced in parallel for confirming mutations in samples that were positive for
      p53 in the PCR-SSCP analysis. The results of these experiments demonstrate that:
      (1) there were mutations in p53 exon 5 and 8 in 35% (14 out of 40 samples) of
      human renal cancer tissues as revealed by PCR-SSCP analysis; (2) DNA sequencing
      of samples showing frame-shift have hot spot of p53 mutation on exon 8 at codon
      244 (GGC-->TGC) and exon 5 at codon 132 [AAG (Lys)-->AGG (Arg)]. This mutation in
      p53 exon 5 at codon 132 is novel and has not yet been reported; (3)
      immunohistochemical staining of p53 in renal cancer tissue using mouse anti-human
      p53 monoclonal antibody, clone PAb 1801, correlated with the p53 mutation
      assessed by PCR-SSCP. No correlation was found between p53 mutations and tumor
      stage and grade of renal cancer.

PMID- 9530524
TI  - In vitro processing of cucumber chloroplast tRNA(Leu)(CAA) precursor in a pea
      chloroplast soluble extract.
AB  - To study the sequential steps in the processing pathway of the chloroplast
      monocistronic intronless tRNA precursors, we examined cucumber chloroplast
      tRNA(Leu)(CAA) processing in a cucumber or pea chloroplast soluble extract. The
      tRNA(Leu)(CAA) precursor synthesized from SP6 RNA polymerase-directed
      transcription system, was used as a substrate. Incubation of the tRNA precursor
      with the pea extract resulted in processing of tRNA(Leu)(CAA) via 5'- and 3'
      endonucleolytic cleavages followed by final trimming of extra 3' nucleotides by
      3' exonuclease(s). No preferred order for endonucleolytic cleavages has been
      observed during the in vitro tRNA(Leu) processing and the simultaneous occurrence
      of the intermediates consisting of leader + tRNA(Leu) and tRNA(Leu) + trailer,
      indicate that either 5'- or 3'-endonucleolytic cleavage can occur as the first
      step in vitro.

PMID- 9530525
TI  - Influence of polyethylene glycol on lactate dehydrogenase.
AB  - It is well established that polyethylene glycol (PEG) shifts the equilibrium in
      oligomeric protein systems to form higher molecular weight associates. We used
      this effect of PEG to evaluate a modification of functional properties of LDH
      from pig skeletal muscles. PEG decreases the rate of heating-induced LDH
      inactivation in the concentration dependent manner. Michaelis constant and
      maximal velocity of the enzyme as well as inhibition of LDH by high pyruvate
      concentrations were affected by PEG. Enzyme preincubation with PEG suppresses
      also the formation of ternary inactive complex NAD-pyruvate-LDH.

PMID- 9530526
TI  - Phase III interlaboratory study of FETAX, Part 2: interlaboratory validation of
      an exogenous metabolic activation system for frog embryo teratogenesis assay-
      Xenopus (FETAX).
AB  - Interlaboratory validation of an exogenous metabolic activation system (MAS)
      developed for the alternative, short-term developmental toxicity bioassay, Frog
      Embryo Teratogenesis Assay-Xenopus (FETAX) was performed with cyclophosphamide
      and caffeine. Seven study groups within six separate laboratories participated in
      the study in which three definitive concentration-response experiments were
      performed with and without the MAS in a side-by-side format for each chemical.
      Since both chemicals had been previously tested in FETAX, the test concentrations
      were provided to each laboratory prior to testing. Interlaboratory coefficient of
      variation (CV) values for unactivated cyclophosphamide (no MAS) were 15%, 15%,
      29%, and 25% for the 96-hr LC50, 96-hr EC50 (malformation), Minimum Concentration
      to Inhibit Growth (MCIG), and Teratogenic Index (TI) values, respectively.
      Addition of the MAS increased the CV values of each endpoint at least 3.9-fold.
      Interlaboratory CV values for unactivated caffeine were 31%, 18%, 31%, and 46%
      for the 96-hr LC50, 96-hr EC50 (malformation), MCIG, and TI values, respectively.
      Addition of the MAS decreased the CV values of each respective endpoint by at
      least 1.6-fold. Results indicated that bioactivated toxicants may be prone to
      greater variability in response amongst laboratories than compounds, which are
      detoxified. Even though more variability was noted with activated
      cyclophosphamide, results were within interlaboratory variation expected for
      other aquatic-based bioassays. Thus, results from these studies warrant the
      continued use and further refinement of FETAX for alternative developmental
      toxicity assessment.

PMID- 9530527
TI  - Evaluation of the developmental toxicities of coumarin, 4-hydroxycoumarin, and 7
      hydroxycoumarin using FETAX.
AB  - The developmental toxicities of coumarin and hydroxycoumarin metabolites were
      evaluated using FETAX. Young X. laevis embryos were exposed to coumarin, 4
      hydroxycoumarin, and 7-hydroxycoumarin in each of two separate concentration
      response experiments with and without an exogenous metabolic activation system
      (MAS) and/or inhibited MAS. The MAS was treated with carbon monoxide (CO),
      cimetidine (CIM), or ellipticine (ELL) to selectively modulate cytochrome P-450
      activity. The MAS was also treated with cyclohexene oxide (CHO) to selectively
      modulate epoxide hydrolase activity. Without the MAS or inhibited MAS, coumarin
      and 7-hydroxycoumarin were nearly equitoxic, whereas 4-hydroxycoumarin was nearly
      2-fold less developmentally toxic than coumarin on an equimolar basis. Addition
      of the MAS and CIM-MAS increased the developmental toxicities of coumarin and,
      particularly, 4-hydroxycoumarin. Addition of the CHO-MAS greatly increased the
      developmental toxicity of coumarin and, especially, 4-hydroxycoumarin. Addition
      of the ELL- or CO-inhibited MAS did not increase the developmental toxicity of
      coumarin. However, addition of the intact MAS did not alter the developmental
      toxicity of 7-hydroxycoumarin. Results from these studies suggested that P-450;
      specifically ELL-inhibited P-450 (arylhydrocarbon hydroxylase) may have been
      responsible for increasing the developmental toxicity of coumarin. Furthermore,
      the increased toxicity of coumarin or 4-hydroxycoumarin following co-incubation
      with CHO-treated microsomes indicated that highly toxic epoxide intermediates may
      be produced from oxidative P-450 metabolism and that epoxide hydrolase may play a
      role in detoxification of the reactive intermediates.

PMID- 9530528
TI  - Changes in the cardiovascular nitric oxide pathway in cyclosporin-A treated rats.
AB  - Cyclosporin A (CsA), an immunosuppressive agent is known to induce cellular toxic
      effects by alerting calcium homeostasis. Nitric oxide (NO) has been implicated in
      a number of physiologic roles in the mammalian cardiovascular system (CVS). The
      aim of our present study is to investigate the effects of CsA on the rat CV NO
      pathway. We measured iNOS and cNOS activities in the 100,000 g soluble fraction
      of ventricles and serum nitrite (NO2-) and nitrite (NO3-) levels in rats treated
      with 25 mg/kg or 50 mg/kg body weight of CsA/24 hr in olive oil. CsA inhibited
      cNOS activity of rat ventricles and failed to bring about changes in their iNOS
      activity. Serum NO2-/NO3- levels were elevated in CsA treated tars. Most of these
      changes were found to be statistically significant (P < 0.01) at 50 mg/kg body wt
      of CsA. It is likely that elevation of serum NO2-/NO3- levels may cause
      myocardial toxicity by alerting rat CV NO pathway.

PMID- 9530529
TI  - Role of GABA receptor complex in low dose lindane (HCH) induced neurotoxicity:
      neurobehavioural, neurochemical and electrophysiological studies.
AB  - Lindane is widely used as an insecticide and scabicide in mammals. High doses in
      chronic exposures caused hyperexcitability and convulsions and impaired motor
      activity involving GABA-ergic mechanism. To investigate the role of
      GABA/Benzodiazepine mechanism in the neurotoxicity of low doses of lindane, rats
      were administered 2, 3, or 5 mg/kg orally for 90 days and behavioural,
      electrophysiological, and neurochemical studies were conducted. The animals
      exposed to lindane exhibited increased geotaxis and decreased spontaneous drug
      induced locomotor activity (which further potentiated by phenobarbitone and
      increased after leptazol). The EEG of the treated rats showed high voltage slow
      wave activity (HVSA) patterns with occasional spindles (9-10 HZ-amplitude of 100
      uv). A significant increase (p < 0.01) in GABA levels in cerebellum and
      significant increase in benzodiazepine receptors in cerebellar membrane measured
      by (3H)flunitrazepam binding were observed in the animals exposed to 3 and 5 mg
      lindane. The study suggests that low dose chronic exposure of lindane causes
      neurobehavioral, neurochemical, and electrophysiological effects involving GABA
      ergic mechanism(s).

PMID- 9530530
TI  - Degree of peroxidative status in neuronal tissues by different routes of
      inorganic mercury administration.
AB  - Mercuric chloride was administered by three routes--subcutaneous, intramuscular
      and intraperitoneal to adult female Wistar rats. The peroxidative status of the
      cerebral cortex, cerebellum and the sciatic nerves were studied. Enhanced levels
      of lipid peroxides indicate progressing cellular injury. All the experimental
      groups show high levels of reduced glutathione and increased activities of
      glutathione peroxidase, superoxide dismutase and catalase. Neurotoxic status was
      more pronounced in intramuscularly administered mercuric chloride, followed
      subsequently by intraperiotoneal and subcutaneous routes of administration.

PMID- 9530531
TI  - Cell proliferation in the livers of male mice and rats exposed to the carcinogen
      P-dichlorobenzene: evidence for thresholds.
AB  - In a previous study, p-dichlorobenzene (pDCB), which is associated with
      tumorigenicity in male rat kidney and livers of mice of both genders, was found
      to produce acute increases in cell proliferation in those tissues. To determine
      whether sustained cell proliferation in the liver in susceptible species
      correlated with reported carcinogenic effects, we examined the effect of pDCB on
      cell proliferation in the livers and toxicity to the glutamine synthetase
      expressing hepatocyte (GS+) subpopulation of male B6C3F1C3F1 mice and F344 rats.
      Mice were exposed for up to 4 weeks to 600, the maximally tolerated dose which
      increased liver tumors, 300 or 150 mg/kg. Rats were exposed to 300, 150 or 75
      mg/kg for up to 4 weeks. In mice, the cumulative replicating fraction (CRF) in
      the livers of the high dose animals was significantly increased 16-fold at 1 week
      and 4-fold at 4 weeks. The CRF was also increased at 300 mg/kg at 1 week, but
      this subsided at 4 weeks. No increase was seen in the low dose group. In rats,
      the CRFs of the livers at 1 week were increased at 300 and 150 mg/kg, but
      returned to normal at 4 weeks. The size of the hepatic GS+ area was not affected
      in mice or in rats after 1 week of exposure, but comparable decreases were
      observed at all exposures at 4 weeks in mice. The data therefore suggest that
      sustained increases of cell division in the mouse liver may contribute to the
      increases in liver tumors. The transient increase in rat liver suggests that this
      is not sufficient to enhance tumor development. The absence of sustained
      increases of the CRFs at the low dose in mice, which was one-fourth of the
      hepatocarcinogenic dose, implies the existence of a threshold in pDCB
      hepatocarcinogenesis.

PMID- 9530532
TI  - Ammoniation to reduce the toxicity of endophyte-infected tall fescue seed fed to
      rats.
AB  - To assess the efficacy of ammoniation in the detoxification of endophyte-infected
      tall fescue (Festuca arundinacea Schreb.), 40 male Harlan Sprague-Dawley rats
      were randomly assigned to the following four treatments for 28 d: endophyte-free
      (E-), endophyte-infected (E+), ammoniated (2% dry matter basis, 7 d) endophyte
      free (AE-), and ammoniated endophyte-infected (AE+) tall fescue seed. Total
      pyrrolizidine alkaloid (N-acetyl and N-formyl loline) and ergovaline contents of
      endophyte-infected fescue seed were reduced 24 and 54%, respectively, by
      ammoniation. Endophyte-infected treatment groups had lower (P < 0.01) daily feed
      intakes (DFI), daily weight gains (DWG), feed effieiencies, and primary serum
      hemagglutination titers to sheep red blood cell (SRBC) immunization than
      endophyte-free treatment groups. Performance parameters were higher (P < 0.01)
      for ammoniated diets in comparison to non-ammoniated die [s; however, anti-SRBC
      titers were not significantly different. When compared to the E+ diet, the AIE+
      diet increased (P < 0.01) DFI (24%), DWG (41%) and feed efficiency (13%).

PMID- 9530533
TI  - Comparison of two ammoniation procedures to reduce the toxicity of endophyte
      infected tall fescue seed fed to rats.
AB  - To determine the effect of extending the duration of ammonia (2% dry matter
      basis) treatment ti'om 1 to 5 wk on the toxicity of endophyte-infected tall
      fescue seed, 60 male Harlan Sprague-Dawley rats were randomly assigned to the
      following six treatments during a 28-d trial: endophyte-free (E-), endophyte
      infected (E+), 1 wk ammoniated endophyte-fee (1AE-), 1 wk ammoniated endophyte
      infected (1AE+), 5 wk ammoniated endophyte-free (5AE-), and 5 wk ammoniated
      endophyte-infected (5AE+) tall fescue seed. The concentration of total
      pyrrolizidine alkaloids (N-acetyl and N-formyl loline) or E+ rescue was reduced
      from 4203 12 g/g to 3009 and 2533 I-tg/g by the 1AE+ and 5AE+ treatments,
      respectively. Ergovaline was lowered from 3.77 to 1.57 12 g/g by 1AE+ and
      eliminated by 5AE+. Endophyte-infected treatment groups had depressed (P <
      0.0001) dally feed intakes (DFI), daily weight gains (DWG), feed efficiencies
      (G/F), primary antibody responses, and T cell and B cell mitogenic responses than
      endophyte-free treatment groups. Ammoniation of endophyte-infected rescue seed
      improved DFI and DWG (P < 0.0001) and G/F (P < 0.05); however, there was no
      difference in performance criteria between the 1-wk and 5-wk ammoniation
      treatments. Endophyte-induced depressions in immune function were not alleviated
      by ammoniation.

PMID- 9530534
TI  - Effect of dietary optimization on growth, survival, tumor incidences and clinical
      pathology parameters in CD Sprague-Dawley and Fischer-344 rats: a 104-week study.
AB  - Controversy regarding the use of ad libitum feeding in chronic rodent toxicity
      studies will soon result in issue of a FDA Points to Consider document. Caloric
      intakes are now recognized to be important uncontrolled variables in bioassays
      because rodents chronically fed ad libitum become obese, reproductively senile
      and have increased incidences of age-related diseases, higher tumor burdens and
      decreased survival. The available literature suggests that ad libitum feeding
      neither optimizes the health and well-being of rodents nor provides the best
      model for use in evaluation of pharmacological and toxicological profiles. Use of
      an optimized diet, restricted in terms of caloric intakes, has been proposed for
      chronic toxicity and carcinogenicity studies in rodents. It is suggested that
      limiting caloric intakes to 50-80% of ad libitum consumption would result in
      lower body weights, decreased tumor incidences and prolonged survival in the
      controls. To evaluate the influence of diet on chronic toxicity and
      carcinogenicity studies in rats, two 104-week studies were conducted. These
      studies consisted of 280 CD Sprague-Dawley and 280 Fischer-344 rats fed ad
      libitum, and 140 CD Sprague-Dawley and 140 Fischer-344 rats fed a diet that was
      optimized by limiting caloric intakes by 15-35%. Both diets consisted of
      certified commercial diet in meal form. The optimized diet reduced weight gain
      approximately 50% after 100 weeks. Clinical chemistry and hematology parameters
      showed negligible effects of reduced diet, with the exception that serum
      triglycerides were lower in males and females in both strains at weeks 52 and
      104. The ad libitum-fed animals had a higher incidence of pseudopregnancy,
      aggressiveness, foot sores and abscesses than the animals fed an optimized diet.
      These effects were more pronounced in the CD Sprague-Dawley rats than in the
      Fischer-344 rats. At the completion of the 104-week study, survival in the ad
      libitum fed CD Sprague-Dawley rats was approximately one-half that of the animals
      fed an optimized diet (39% versus 76%). The difference in survival between
      Fischer-344 rats fed ad libitum and those fed an optimized diet was less
      pronounced (78% versus 89%). A reduced incidence of palpable tissue masses in the
      ad libitum-fed CD Sprague-Dawley rats versus the animals fed an optimized diet
      reflected inability to detect small masses in the obese ad libitum-fed animals.
      In contrast, the leaner Fischer-344 ad libitum-fed animals had an increased
      incidence of palpable tissue masses. After 52 weeks, 40 animals from each strain
      and feeding regimen were killed and subjected to complete necropsy and
      histopathological examination; the remainder of the survivors was examined at the
      completion of the study (104 weeks). Use of an optimized diet substantially
      reduced the incidences of endocrine-mediated tumors in both rat strains and
      delayed the onset of leukemia in Fischer-344 rats. These results indicate the
      need to further investigate the relationship of increased caloric intakes and
      endocrine-mediated or strain specific tumors and support FDA's and others'
      positions that use of diet optimization in chronic toxicity and carcinogenicity
      rodent bioassays has the potential to remarkably improve the scientific quality
      and relevance of these studies. It also identified that the small increases in
      cost associated with diet optimization are far exceeded by the advantages of
      increased survival of animals, reduced intercurrent disease and rumor burdens,
      and increased ease of histopathological processing and evaluation.

PMID- 9530536
TI  - A risk-benefit assessment of treatment with finasteride in benign prostatic
      hyperplasia.
AB  - As an androgen target organ, the prostate gland has the almost unique
      characteristic of being less sensitive to testosterone than to its metabolite 5
      alpha-dihydrotestosterone (5 alpha-DHT). The conversion of testosterone to 5
      alpha-DHT is induced by the enzyme 5 alpha-reductase. By blocking the activity of
      5 alpha-reductase, the androgenic stimulation of the prostate gland can be
      significantly reduced. The first drug with such capacity to be introduced on the
      market was finasteride. Following the administration of this drug to men, serum 5
      alpha-DHT levels were reduced by approximately 80%. Large phase III trials have
      demonstrated the efficacy of finasteride in treating benign prostatic hyperplasia
      (BPH). While in some patients the drug was poorly effective, other patients
      showed significant improvements. The mean reduction in size of the prostate gland
      was 20 to 25% after 6 months of therapy, and this effect was maintained as long
      as the patient was on the drug, at least up to the end of a 6-year follow-up
      period. Prostatic symptom scores were improved by a mean of 30%, while urinary
      flow was only improved by a mean of 1.5 ml/sec (15%). In a recent double-blind,
      placebo-controlled study comparing the alpha-blocker terazosin with finasteride,
      significant improvement was demonstrated for the alpha-blocker, while finasteride
      produced little improvement overall and was not significantly more effective than
      placebo in treating moderately symptomatic BPH. However, a subanalysis of this
      study showed that while finasteride was poorly effective in patients with small
      prostate glands, a significant improvement was apparent in those with glands
      larger than 40 ml. There is some evidence that early intervention with
      finasteride can reduce the number of surgical procedures that are required, at
      least over a 2-year period. Finasteride is very well tolerated. However, since 5
      alpha-DHT potentiates erectile capacity, a 3 to 4% incidence of impotence has
      been reported, as well as a decreased ejaculatory volume. Gynaecomastia has been
      noted in a few patients (0.4%). In conclusion, finasteride appears to be a very
      well tolerated drug to treat outflow obstruction in patients with moderately
      symptomatic BPH caused by large prostate glands.

PMID- 9530535
TI  - The application of adverse drug reaction data to drug choice decisions made by
      pharmacy and therapeutics committees. An Australian perspective.
AB  - Pharmacy and Therapeutics (P&T) committees undertake policy, regulatory and
      educational activities to promote rational use of medicines in their institutions
      with the aim of improving the quality of health and economic outcomes at these
      institutions. Formulary management is an important part of the P&T committees'
      activities and making drug choices is one of the committees' most difficult
      tasks. The 3 types of information most commonly identified by P&T committees as
      necessary for making drug choices are effectiveness, safety and cost data;
      usually in this order of importance. There is some evidence, however, that safety
      data are not considered by all committees when they make decisions about adding a
      new drug to a formulary. The role of adverse drug reaction (ADR) data in
      formulary decision-making (for registered drugs) occurs at several levels. First,
      ADR data obtained from pre-marketing studies of the drug are important and enable
      the committee to make an assessment of the risk of toxicity that should be
      anticipated for the drug. However, the limited nature of this information makes
      an absolute assessment impossible. Secondly, comparative safety information is
      necessary when deciding the place in therapy of a particular drug. Weighing up
      the comparative risks and benefits is a complex task which is a routine activity
      for most P&T committees whatever level of sophistication is applied. Thirdly, ADR
      data are an important ingredient of any economic assessment considered by a P&T
      committee. Calculation of the costs and consequences associated with the adverse
      effects of treatment demand careful assessment. Finally, aggregated adverse drug
      event reports which collate not only the consequences of adverse drug reactions
      but also medication incidents (medication errors) and which have been reported
      locally can be a useful quality assurance process for a P&T committee. This
      information will contribute to the identification of drugs for deletion from the
      formulary and less commonly in making decisions about additions to the formulary.
      As formulary management forms only part of a P&T committee's work, so the
      committee's interest in ADR is broader than the use of these data in making drug
      choices. The P&T committee may also be involved in promoting ADR reporting to
      either a central database or primary carers. Although often of limited
      availability, ADR information has an important role in the formulary management
      process of P&T committees.

PMID- 9530539
TI  - Diabetes mellitus in pregnancy. What are the best treatment options?
AB  - Diabetes mellitus complicates somewhere between 1 and 20% of all pregnancies
      worldwide. Women with all types of diabetes, including type 1 (insulin-dependent)
      and type 2 (non-insulin-dependent) diabetes mellitus, and gestational diabetes
      mellitus, as well as their infants, are at increased risk for a number of
      different complications. However, achieving and maintaining euglycemia throughout
      gestation has been demonstrated to reduce the risk of adverse outcome for both
      the mother and her offspring. Traditional management approaches use a combination
      of diet, exercise, intensive insulin regimens and multiple self monitored blood
      glucose determinations. There are a number of newer agents available to treat
      diabetes mellitus; however, their safety in pregnancy has not been thoroughly
      tested. Although the oral hypoglycaemic drugs are not customarily used during
      gestation in most of the US and Europe they have had considerable use in South
      Africa. Animal and human studies of the teratogenic effects of these drugs have
      yielded conflicting data and it is difficult to distinguish between the
      teratogenic effects of poor maternal metabolic control and the agents themselves.
      This article also addresses the current state of the knowledge regarding the drug
      safety of a variety of medications for conditions, including hypertension and
      preterm labour, commonly encountered in the management of the pregnant women with
      diabetes mellitus.

PMID- 9530540
TI  - Risk factors for the spread of antibiotic-resistant bacteria.
AB  - The emergence of antibiotic resistance is primarily due to excessive and often
      unnecessary use of antibiotics in humans and animals. Risk factors for the spread
      of resistant bacteria in hospitals and the community can be summarised as over
      crowding, lapses in hygiene or poor infection control practices. Increasing
      antibiotic resistance in bacteria has been exacerbated by the slow pace in
      developing newer antibiotics. Methicillin-resistant Staphylococcus aureus (MRSA),
      vancomycin-resistant enterococci (VRE) and multiresistant Gram-negative bacteria
      are spread primarily by direct or indirect person-to-person contact. Independent
      risk factors for MRSA include the use of broad spectrum antibiotics, the presence
      of decubitus ulcers and prosthetic devices while those for VRE include prolonged
      hospitalisation and treatment with glycopeptides or broad spectrum antibiotics.
      For the spread of resistant Gram-negative bacteria risk factors include urinary
      catheterisation, excessive use of antibiotics and contamination of humidifiers
      and nebulisers. The spread of penicillin-resistant pneumococci (PRP) and drug
      resistant and multidrug-resistant tuberculosis (MDRTb) is due to airborne
      transmission. Risk factors for the spread of PRP include overcrowding,
      tracheostomies and excessive use of penicillins for viral respiratory infections;
      for MDRTb they include poor compliance, convergence of immunosuppressed patients,
      delayed diagnosis or treatment, and poor or inadequate ventilation and isolation
      facilities. Recent developments in the genomic mapping of many bacteria and
      advances in combinatorial chemistry promise to usher in a new era of antibiotic
      development. While this may result in our regaining some of the ground lost to
      resistant bacteria, there will still be a continuing need to minimise the spread
      of antibiotic resistance through the rational use of antibiotic agents and
      stringent infection control practice.

PMID- 9530537
TI  - ACE inhibitor-induced angioedema. Incidence, prevention and management.
AB  - Available information from 1980 to 1997 on angiotensin converting enzyme (ACE)
      inhibitor-induced angioedema and its underlying mechanisms are summarised and
      discussed. The incidence of angioedema is low (0.1 to 0.2%) but can be considered
      as a potentially life-threatening adverse effect of ACE inhibitor therapy. This
      adverse effect of ACE inhibitors, irrespective of the chemical structure, can
      occur early in treatment as well as after prolonged exposure for up to several
      years. The estimate incidence is quite underestimated. The actual incidence can
      be far higher because of poorly recognised presentation of angioedema as a
      consequence of its late onset in combination with usually long term therapy.
      Also, a spontaneous reporting bias can contribute to an actual higher incidence
      of this phenomenon. The incidence can be even higher (up to 3-fold) in certain
      risk groups, for instance Black Americans. Treatment includes immediate
      withdrawal of the ACE inhibitor and acute symptomatic supportive therapy followed
      by immediate (and long term) alternative therapy with other classes of drugs to
      manage hypertension and/or heart failure. Preclinical and clinical studies for
      the elucidation of the underlying mechanism(s) of ACE inhibitor-associated
      angioedema have not generated definite conclusions. It is suggested that
      immunological processes and several mediator systems (bradykinin, histamine,
      substance P and prostaglandins) are involved in the pathogenesis of angioedema. A
      great part of all reviewed reports suggest a relationship between ACE inhibitor
      induced angioedema and increased levels of (tissue) bradykinin. However, no
      conclusive evidence of the role of bradykinin in angioedema has been found and an
      exclusive role of bradykinin seems unlikely. So far, no clear-cut evidence for an
      immune-mediated pathogenesis has been found. In addition, ACE gene polymorphism
      and some enzyme deficiencies are proposed to be involved in ACE inhibitor-induced
      angioedema. Progress in pharmacogenetic and molecular biological research should
      throw more light on a possible genetic component in the pathogenesis of ACE
      inhibitor-associated angioedema.

PMID- 9530538
TI  - Behavioural toxicity of medicinal drugs. Practical consequences, incidence,
      management and avoidance.
AB  - Behavioural toxicity is relatively common among medicinal drug users and evidence
      shows that drugs frequently produce adverse effects that prevent their users from
      performing everyday operations in a normal manner. Epidemiological research
      generally indicates that the use of sedative drugs is associated with an
      increased risk of becoming involved in injurious accidents. Empirical studies
      have also demonstrated adverse effects of sedative drugs on the performance of
      healthy volunteers and patients in laboratory tests designed to measure
      psychomotor and cognitive function, and in real life-tests measuring on-the-road
      driving performance. Empirical studies also indicate that behavioural toxicity
      can vary widely between individual drugs depending on differences in dose, dosing
      regimen, duration of treatment, pharmacokinetics or mechanisms of actions.
      Besides sedation, other CNS adverse effects such as aggression, paranoia, social
      withdrawal or lack of motivation may disrupt or prevent the initiation of normal
      performance, thus imposing a burden on the ability of the patients to function in
      a normal manner. Emotional disturbances are rare as indicated by the small number
      of case reports that mention their existence. Yet theses disturbances sometimes
      involve severe reactions that are more debilitating than sedation. Behavioural
      toxicity can be minimised by avoidance of pharmacodynamic and pharmacokinetic
      drug interactions, adjustment of dosage regimens to a patient's individual
      response to a drug, nocturnal administration of drugs that are expected to
      produce sedation and patient education on the potential risks of the drugs they
      receive. Much of this information can be gained from experimental literature
      comparing the effect of individual drugs on performance. Unfortunately this is
      presently incomplete, since most research on behavioural toxicity has been
      confined to psychiatric drugs. Yet, in the interest of the patient, it should be
      the responsibility of drug manufacturers and regulators to always identify
      problematic drugs.

PMID- 9530541
TI  - Current treatment recommendations in antiarrhythmic therapy.
AB  - Over the past decade, various studies have demonstrated that class I
      antiarrhythmic drugs should be avoided in patients with heart failure, cardiac
      ischaemia or a previous myocardial infarction. In contrast, class II drugs (beta
      blockers) reduce morbidity and may even lower mortality in patients suffering
      from moderate to severe heart failure. In these patients, careful titration of
      the drug dosage, frequently during hospital admission, may be necessary. If in
      the setting of heart failure ventricular arrhythmias are symptomatic and/or
      sustained, patients can be treated effectively, after appropriate treatment of
      the underlying disease, with the class III drug amiodarone. Unfortunately, this
      drug does not lower overall mortality, implying that prophylactic institution of
      amiodarone is not indicated. Pure class III antiarrhythmic drugs like d-sotalol,
      ibutilide and dofetilide show a high rate of torsade de pointes. Currently, only
      ibutilide has been approved for clinically monitored intravenous administration.
      Class IV drugs, the calcium channel blockers, are still very useful for rate
      control of atrial fibrillation and conversion or prevention of atrioventricular
      nodal re-entrant tachycardias and circus movement tachycardias using a
      (concealed) bypass tract. Finally, an implantable cardioverter defibrillator
      seems to improve overall survival in patients with life-threatening ventricular
      arrhythmias. This may imply that an increasing number of patients will be
      candidates for such a device. However, it will be necessary to await publication
      of data involving these devices from current ongoing studies.

PMID- 9530542
TI  - Meningococcal vaccines. Current status and future possibilities.
AB  - Meningococcal disease causes great emotion and anxiety in the families and
      caregivers of patients. Numbers of such patients are usually small in
      industrialised countries, unlike those in many regions--especially in subsahelian
      Africa. Vaccines have been tried for more than 80 years; at present there are
      available polysaccharide vaccines against groups A, C, Y and W135, and a protein
      based vaccine against group B. A property common to all is their relative
      efficacy (75 to 100%) at school age and after, and an acceptably short
      persistence of antibodies. Small children pose the major challenge, in whom there
      is essentially evidence of clinical protection only against group A and C
      diseases. With vaccines against other serogroups protection is possible, but not
      yet proven in controlled clinical studies. The search is on for help from various
      modifications, including the conjugation technique, to transform the independent
      nature of polysaccharide response towards T cell dependence, as was done earlier
      in Haemophilus influenzae type b vaccines. First trials along this path are
      encouraging although, again, group B meningococci pose special problems. The next
      few years will probably see a new generation of meningococcal vaccines. Generally
      speaking, the incidence of meningococcal disease is too low to indicate
      vaccinations for the whole population, or even children, but some risk groups and
      epidemics are important exceptions. To date, bivalent group A + C or tetravalent
      group A + C + Y + W135 polysaccharides, or an outer membrane protein-based group
      B vaccine, are the products to be used when the indications, that may vary from
      country to country, are considered met. A strong herd immunity effect,
      demonstrated with group A and C vaccinations, facilitates extinction of an
      epidemic since large-scale vaccinations can be restricted only in the major risk
      groups, children and in various schools. Prompt intervention demands, however, a
      functioning mechanism which detects very early on a pending epidemic.
      Unfortunately, such a mechanism is often lacking in countries often hit by this
      deadly disease.

PMID- 9530543
TI  - Practical considerations in the treatment of hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) represents one of the most common neoplasms
      worldwide. To date, curative treatment options include liver transplantation or
      resection. Unfortunately, most patients are detected with nonresectable or 
      transplantable HCC due to disease extension or comorbid factors, and are
      therefore candidates only for palliative treatments. Palliative medical
      treatments, including systemic chemotherapy, immunotherapy or hormonal
      manipulation, have a borderline activity on HCC and cannot be recommended outside
      clinical trials. A high response rate has been reported with local therapies such
      as transcatheter arterial embolisation, intra-arterial chemotherapy or
      percutaneous alcohol (ethanol) injection, but as there is no clear evidence of a
      survival advantage for these treatment modalities, further investigations are
      required. Multidisciplinary treatment, including preoperative cytoreduction or
      postoperative adjuvant therapy, is currently under investigation, with
      encouraging survival results. HCC patients should be evaluated within clinical
      trials, possibly randomised and with homogeneous prognostic factors, in order
      that we may find the answer to all these important questions.

PMID- 9530545
TI  - Butenafine.
AB  - Butenafine is a new antifungal agent with primary fungicidal activity against
      dermatophytes such as Trichophyton mentagrophytes, Microsporum canis and
      Trichophyton rubrum which cause tinea infections. 14C-labelled butenafine
      (approximately 30 micrograms/g tissue) was found within guinea-pig dorsal skin 24
      hours after topical application. Most of the drug was distributed into the
      epidermis including the horny layer. Small amounts were found in the dermis,
      probably transported via sebaceous glands and hair follicles. In vitro, the
      minimum concentration that completely inhibited growth of dermatophytes (MIC) and
      the minimum fungicidal concentrations (MFC) for butenafine against T.
      mentagrophytes and M. canis were similar (0.012 to 0.05 mg/L) and were 4 to 130
      times lower than those for naftifine, tolnaftate, clotrimazole and bifonazole. It
      also has greater activity against T. rubrum, M. gypseum and Epidermophyton
      floccosum when compared with naftifine, tolnaftate and clotrimazole; comparisons
      with bifonazole against these strains were not available. Assessment after 1
      week's treatment in patients with tinea pedis revealed that mycological cure
      rates were greater in those who received twice-daily butenafine for 1 week or
      once-daily butenafine for 4 weeks than in placebo recipients. Mycological and
      overall cure rates were either further increased or maintained up to 5 weeks
      after treatment cessation compared with end-of-treatment values. In patients with
      tinea cruris or tinea corporis who received once-daily butenafine 1% for 2 weeks,
      the mycological and overall cure rates continued to increase for up to 4 weeks
      after treatment cessation.

PMID- 9530546
TI  - Cerivastatin.
AB  - Cerivastatin is a synthetic HMG-CoA reductase inhibitor with high liver
      selectivity, which lowers plasma cholesterol levels by inhibiting endogenous
      cholesterol synthesis. In vitro, the affinity of cerivastatin for HMG-CoA
      reductase was higher than that of lovastatin, simvastatin and pravastatin. This
      higher enzyme affinity was reflected in vivo, with a lower ED50 (dose causing 50%
      inhibition) for cerivastatin in rats and beagle dogs compared with lovastatin.
      Cerivastatin 0.2 mg/day significantly reduced low density lipoprotein (LDL)
      cholesterol, total cholesterol and triglyceride levels, and increased high
      density lipoprotein (HDL)-cholesterol levels, in patients with type IIa
      hypercholesterolaemia. Available data indicate that cerivastatin has a
      tolerability profile similar to that of other HMG-CoA reductase inhibitors. No
      drug interactions were observed when cerivastatin was coadministered with
      digoxin, warfarin, cimetidine or the antacid magnesium/aluminium hydroxide.

PMID- 9530544
TI  - Antiretroviral therapy for HIV infection. A knowledge-based approach to drug
      selection and use.
AB  - In the absence of evidence that eradication of HIV from an infected individual is
      feasible, the established goal of antiretroviral therapy is to reduce viral load
      to as low as possible for as long as possible. Achieving this with the currently
      available antiretroviral agents involves appropriate selection of components of
      combination regimens to obtain an optimal antiviral response. In addition,
      consideration of a plan for a salvage or second-line regimen is required if
      initial therapy fails to achieve an optimal response or should loss of
      virological control occur despite effective initial therapy. Such a planned
      approach, based on consideration of the likely modes of therapeutic failure
      (viral resistance, cellular resistance, toxicity) could be called rational
      sequencing. Choice of therapy should never involve compromise in terms of
      activity. However, the choice of drug should also be guided by tolerability
      profiles and considerations of coverage of the widest range of infected cells,
      compartmental penetration, pharmacokinetic interactions and, importantly, the
      ability of an agent or combination to limit future therapeutic options through
      selection of cross-resistant virus. Available clinical end-point data clearly
      indicate that combination therapy is superior to monotherapy, with clinical and
      surrogate marker data supporting the use of triple drug (or double protease
      inhibitor) combinations over double nucleoside analogue combinations. Thus, 3
      drug therapy should represent current standard practice in a nontrials setting.
      Treatment should be considered as early as practical, and may be best guided by
      measurement of viral load, with a range of other markers having potential utility
      in individualising treatment decisions. Therapeutic failure may be defined
      clinically, immunologically or, ideally, virologically, and should prompt
      substitution of at least 2, and preferably all, components of the treatment
      regimen. Drug intolerance may also be best managed by rational substitution.

PMID- 9530547
TI  - Raltitrexed. A review of its pharmacological properties and clinical efficacy in
      the management of advanced colorectal cancer.
AB  - Raltitrexed (ZD-1694) is a quinazoline-based folate analogue that exerts its
      cytotoxic activity by the specific inhibition of thymidylate synthase. In vitro
      studies show that raltitrexed is actively transported into cells and is then
      rapidly and extensively metabolised to a series of polyglutamates. These
      metabolites are significantly more potent inhibitors of thymidylate synthase than
      the parent drug and are retained intracellularly, producing prolonged cytotoxic
      effects without the need for continuous drug exposure. Phase III clinical trials
      in patients with advanced colorectal cancer evaluated raltitrexed 3 mg/m2
      administered as a 15-minute intravenous infusion once every 3 weeks. This
      schedule produced objective response rates of 14.3 to 19.3%, which were similar
      to those in patients treated with fluorouracil plus leucovorin (15.2 to 18.1%).
      Median survival durations ranged from 9.7 to 10.9 months with raltitrexed
      treatment and from 10.2 to 12.7 months with fluorouracil plus leucovorin. The
      major toxicities associated with raltitrexed involve the haematological and
      gastrointestinal systems, although severe asthenia also occurred in 6 to 18% of
      patients receiving the drug. Grade 3 or 4 nausea or vomiting occurred in up to
      13% of raltitrexed recipients and grade 3 or 4 diarrhoea in up to 14%. Similar
      incidences of grade 3 or 4 nausea or vomiting and diarrhoea were seen with
      fluorouracil plus leucovorin treatment. Raltitrexed generally showed significant
      advantages over fluorouracil plus leucovorin with respect to the incidence of
      leucopenia and mucositis. A greater proportion of raltitrexed than fluorouracil
      plus leucovorin recipients were able to receive the scheduled dosage. Thus, with
      its similar efficacy to fluorouracil-based regimens, convenient administration
      schedule and favourable tolerability profile, raltitrexed provides clinicians
      with a worthwhile alternative to fluorouracil-based treatment for patients with
      advanced colorectal cancer.

PMID- 9530550
TI  - [Possible phantom pain from childhood extremity aplasia].

PMID- 9530548
TI  - Tiagabine. A review of its pharmacodynamic and pharmacokinetic properties and
      therapeutic potential in the management of epilepsy.
AB  - Tiagabine is a gamma-aminobutyric acid (GABA) uptake inhibitor which is
      structurally related to nipecotic acid but has an improved ability to cross the
      blood-brain barrier. Clinical trials have shown that tiagabine is effective as
      add-on therapy in the management of patients with refractory partial epilepsy. In
      short term studies of this indication, tiagabine < or = 64 mg/day for 7 to 12
      weeks reduced the complex partial and simple partial seizure frequency by > or =
      50% in 8 to 31 and 28.2 to 37% of patients, respectively. Tiagabine appeared to
      produce a sustained reduction in seizure frequency in studies of up to 12 months'
      duration. Data from preliminary studies are currently insufficient to confirm the
      usefulness of tiagabine when used as monotherapy or in the treatment of children
      with epilepsy. Further studies are, therefore, necessary to more fully elucidate
      the efficacy of the drug in these settings. Adverse events associated with
      tiagabine are primarily CNS-related and include dizziness, asthenia, nonspecific
      nervousness and tremor. Skin rash or psychosis occurred with similar frequencies
      among tiagabine- and placebo-treated patients. With long term administration (>
      or = 1 year for many patients), the profile and incidence of adverse events was
      similar to that for short term therapy. Tiagabine does not appear to affect the
      hepatic metabolism of other drugs such as carbamazepine and phenytoin. Possible
      disadvantages of tiagabine include its short plasma elimination half-life,
      necessitating 2 to 4 times daily administration, and its inducible hepatic
      metabolism. Thus, tiagabine is a new antiepileptic agent with a novel mechanism
      of action, which has demonstrated efficacy in the adjunctive treatment of
      patients with refractory partial epilepsy. Further investigation of the efficacy
      of tiagabine is expected to provide a clearer definition of its place in the
      treatment of epilepsy and its relative merits in relation to other antiepileptic
      drugs.

PMID- 9530549
TI  - Saquinavir soft-gel capsule formulation. A review of its use in patients with HIV
      infection.
AB  - Saquinavir is an HIV protease inhibitor which, formulated as a hard-gel capsule
      (HGC), was the first drug of its class to become available for the treatment of
      patients with HIV infection. Despite the beneficial effects that saquinavir HGC
      containing combination regimens have shown in the treatment of patients with HIV
      infection, the HGC formulation has limited oral bioavailability and has shown
      only modest antiviral activity in vivo. To overcome this limitation (with the aim
      of improving antiviral efficacy), a soft-gel capsule (SGC) formulation of the
      drug has been developed. At the recommended dosage of 1200 mg 3 times daily, the
      SGC formulation of saquinavir achieves plasma concentrations > 8 times higher
      than those in patients receiving saquinavir HGC 600 mg 3 times daily. Initial
      results of trials evaluating the therapeutic efficacy of saquinavir SGC
      containing combination therapy in patients with moderate to advanced HIV
      infection are promising. In patients who were previously antiretroviral therapy
      naive or -experienced, short term (< or = 36 weeks) treatment with saquinavir SGC
      in combination with > or = 2 nucleoside reverse transcriptase inhibitors (NRTIs),
      or nelfinavir, or 2 NRTIs plus nelfinavir led to marked improvements in
      virological and immunological markers of HIV disease. In comparative trials,
      saquinavir SGC showed improved antiviral activity compared with the HGC
      formulation in terms of reducing viral load. Furthermore, saquinavir SGC in
      combination with 2 NRTIs was as effective as indinavir plus 2 NRTIs in
      antiretroviral-naive or -experienced patients. Available data suggest that
      saquinavir SGC-containing combination therapy may be of greatest benefit in
      patients naive to previous antiretroviral therapy. The SGC formulation of
      saquinavir appears to be generally well tolerated by adults with HIV infection.
      Gastrointestinal adverse events, notably diarrhoea, abdominal discomfort, nausea
      and dyspepsia, are the most common adverse events occurring during treatment with
      the drug. Initial results of several trials that used surrogate markers to assess
      treatment efficacy indicate that the SGC formulation of saquinavir, administered
      in combination with other antiretroviral drugs, is an effective and well
      tolerated treatment for patients with moderate or advanced HIV infection.
      Although further data are required before definitive conclusions can be drawn
      regarding the comparative efficacy and tolerability of the SGC and HGC
      formulations, it appears likely that the SGC formulation will replace the
      conventional formulation as a component of combination regimens for the treatment
      of patients with HIV infection.

PMID- 9530551
TI  - [The concept of cycloid psychoses. Developments, clinical significance and the
      state of research].
AB  - Karl Leonhard developed the concept of cycloid psychoses by further elaborating
      previous findings of Carl Wernicke and Karl Kleist. A phasic alternating and
      recurrent as well as remittent course without residual states and a bipolar and
      polymorphous symptomatology are main features of cycloid psychoses. The symptom
      constellations are typical in a manner that, in most cases, allows establishing a
      diagnosis solely by carefully examining a cross-section of the clinical
      syndromes. 3 sub-forms are differentiated. Anxiety-happiness psychosis is
      characterised by extreme affective alterations with paranoid anxiety on the one
      hand and ecstasy with feelings of elation on the other. Formal thought disorder
      with incoherence, mainly as "incoherence of thematic choice", on the excited pole
      and perplexedness on the inhibited pole are the central elements of confusion
      psychosis. Motility psychosis shows hyperkinesis or akinesis of a purely
      psychomotor nature affecting predominantly expressive and reactive motions as
      main features. A description of Leonhard's highly operationalised diagnostic
      criteria for each sub-form of cycloid psychoses is followed by an account of the
      clinical significance of the concept of cycloid psychoses. Furthermore, important
      findings of recent research are summarised. The findings point to the fact that
      cycloid psychoses represent a nosological entity that can be clearly separated
      from schizophrenic as well as from affective psychoses. Schizophreniform,
      schizoaffective or acute transient psychotic disorders are also not identical
      with cycloid psychoses. According to the criteria of DSM-IV or ICD-10, cycloid
      psychoses are spread over a broad spectrum of heterogeneous diagnoses, thus
      hampering the recognition of the clinical and scientific importance of this
      homogeneous group of psychoses.

PMID- 9530553
TI  - [Subsyndromes in chronic schizophrenia. The heterogeniety of schizophrenic
      psychoses].
AB  - Recent psychopathological studies consistently identified a delusional, a
      negative, and a disorganised subsyndrome in chronic schizophrenia.
      Neuropsychological studies found the delusional sub-syndrome to be associated
      with an impaired delayed recognition, while the negative subsyndrome showed a
      marked deficit in delayed recall. In addition, the delusional and the negative
      subsyndromes shared procedural memory changes. The disorganised subsyndrome was
      associated with neurological soft signs and a poor working memory performance.
      Following neuroimaging studies, the delusional subsyndrome showed a significantly
      reduced hippocampal activity, while the asthenic sub-syndrome presented with a
      pronounced hypofrontality and significantly decreased activity in the corpus
      callosum. At the same time, both subsyndromes were associated with a decreased
      activity in the anterior cingulum and medial frontal cortex. The disorganised
      subsyndrome corresponded with an increased activity in the parietal cortex and
      motor strip. When compared with the healthy controls, these findings were not
      specific for the respective subsyndrome, since they were observed among all
      schizophrenics, but to a different extent. It is suggested that the subsyndromes
      of chronic schizophrenia represent psychopathological dimensions which may co
      occur in the individual patient.

PMID- 9530552
TI  - [Hereditary neural amyotrophy (HNA): clinical and molecular genetic basis].
AB  - Hereditary neuralgic amyotrophy (HNA) and hereditary neuropathy with liability to
      pressure palsies (HNPP) are hereditary focal neuropathies. In this study we
      describe three families suffering from HNA. These families were examined
      clinically and electrophysiologically. Linkage analysis with markers from distal
      chromosome 17 was performed in a three-generation family. HNA could be separated
      from HNPP in all three families based on clinical and electrophysiological
      findings. HNA was characterised by recurrent episodes of painful brachial plexus
      lesions. In contrast to HNPP, no evidence for generalised neuropathy was found in
      the HNA families. Linkage analysis confirmed the HNA locus on distal chromosome
      17. Additionally, we were able to refine the HNA locus to a 16 cM region on
      chromosome 17q24-q25.

PMID- 9530554
TI  - [The effect of selective serotonin-reuptake inhibitors in blood coagulation].
AB  - Nowadays, Selective Serotonin Reuptake Inhibitors (SSRI) are well established in
      psychopharmacological therapy. They have been shown to be very effective and
      having a favourable side effect profile. However, bleeding events are rare but
      there may be potentially severe complications under treatment with SSRI. These
      complications can occur under SSRI alone and in combination with anticoagulative
      drugs, whereas the coagulation parameters can remain unchanged.
      Pathophysiologically these bleeding complications are related to a reduced
      concentration of serotonin in the blood and platelets. Reduction of serotonin,
      which occurs under treatment with SSRI, can lead to disturbances of platelet
      function and may also activate the fibrinolytic system. Both effects increase the
      risk of bleeding complications. In combination with anticoagulants, besides the
      serotonin-related bleeding events, additionally influences of SSRI on metabolism
      of the anticoagulative drugs due to their interactions with the Zytochrom-P450
      system and changes of free plasma levels of the anticoagulative drugs, caused by
      a displacement from the plasma proteins through the SSRI, must be taken into
      consideration.

PMID- 9530555
TI  - [The future of diagnosis in psychiatry].
AB  - Following a brief introduction to the history of psychiatric classification, the
      article describes the development of the international classification of diseases
      as a whole, especially ICD-10 as a model of operationalised diagnosis, and
      reports on the corresponding development of DSM-III to DSM-IV. A future task is
      the foundation of a new nosology that will include aetiology in the framework of
      operationalised diagnosis. Atheoretical diagnosis as proposed nowadays according
      to ICD-10 will remain fictitious. Dimensional diagnoses and multiaxiality will
      gain in importance, especially in the category of neurotic and personality
      disorders. Psychiatry in primary health care will be much more important than it
      is today, as will rehabilitation in psychiatry. The paper concludes with the hope
      that the next generation will benefit from a single worldwide classification of
      diagnosis and that the schism between ICD-10 and DSM-IV will be overcome.

PMID- 9530556
TI  - [Motor activity and subjective findings in depressive patients].
AB  - Intensity of symptoms including mood and psychomotor activity has been shown to
      vary according to the time of the day in a group of depressed patients. This
      pattern represents one diagnostic criterion for the melancholic type of
      depression. The variation of intensity is experienced by the patient and can be
      observed as a behavioral symptom. However, the relation of circadian alterations
      in psychomotor activity and depressed mood remains unclear. Therefore,
      spontaneous motor activity and experienced intensity of symptoms were measured in
      21 depressed patients who showed daily variations of subjective symptoms.
      Patients felt significantly less active, awake, and more depressed in the morning
      compared to the evening. However, corresponding activity levels, which were
      measured by actigraphy, appeared significantly higher in the morning compared to
      the evening. Increased motor activity could represent the observable behavioral
      equivalent of self-experienced psychomotor retardation and depressed mood.

PMID- 9530557
TI  - The TH1/TH2 paradigm in allergy.
AB  - Recent evidence has been accumulated to suggest that allergen-reactive type 2
      helper T cells (Th2) play a triggering role in the activation and/or recruitment
      of IgE antibody-producing B cells, mast cells and eosinophils, i.e. the cellular
      triad involved in the allergic inflammation. Interleukin (IL)-4 production by a
      still unknown cell type (T cell subset, mast cell/basophil?) at the time of
      antigen presentation to the Th cell is critical for the development of Th2 cells.
      Other cytokines, such as IL-1 and IL-10, and hormones, such as calcitriol and
      progesterone, also play a favoring role. In contrast, cytokines such as
      interferon (IFN-alpha, IFN-gamma, IL-12 and transforming growth factor (TGF)
      beta, and hormones, play a negative regulatory role on the development of Th2
      cells. However, the mechanisms underlying the preferential activation by
      environmental allergens of Th2 cells in atopic individuals still remain obscure.
      Some gene products selectively expressed in Th2 cells or selectively controlling
      the expression of IL-4 have recently been described. Moreover, cytokines and
      other gene products that dampen the production of IL-4, as well as the
      development and/or the function of Th2 cells, have been identified. These
      findings allow us to suggest that the up-regulation of genes controlling IL-4
      expression and/or abnormalities of regulatory mechanisms of Th2 development
      and/or function may be responsible for Th2 responses against common environmental
      allergens in atopic people. The new insights in the pathophysiology of T cell
      responses in atopic diseases provide exciting opportunities for the development
      of novel immunotherapeutic strategies. They include the induction of
      nonresponsiveness in allergen-specific Th2 cells by allergen peptides or
      redirection of allergen-specific Th2 responses by Th1-inducing cytokines, altered
      peptide ligands, allergens incorporated into recombinant microorganisms or bound
      to appropriate adjuvants, and plasmid DNA vaccination. In severe atopic patients,
      the possibility of nonallergen-specific immunotherapeutic regimens designed to
      target Th2 cells or Th2-dependent effector molecules, such as specific IL-4
      transcription factors, IL-4, IL-5 and IgE, may also be suggested.

PMID- 9530558
TI  - Determination of T-lymphocyte adhesion to endothelial cells using a novel
      luminescence marker.
AB  - Here we report the quantification of T cell adhesion to endothelial cells using
      the luminescence marker BioLite. A new application for this substance was
      established using a microassay for the detection of TK-1 mouse T-lymphoma cell
      adhesion to unstimulated or TNF alpha-stimulated eEnd.2 mouse vascular
      endothelioma cells. Prelabelling of TK-1 with the marker resulted in luminescence
      values linearly related to the number of adherent T cells. The marker was not
      toxic for T cells or endothelial cells nor did it interfere with the expression
      or function of adhesion molecules on T cells (LFA-1, VLA-4) or endothelial cells
      (ICAM-1, VCAM-1). When compared with established techniques to quantify T
      cell/endothelial cell adhesion, i.e. microscopical evaluation or isotope
      prelabelling of T cells, this method was found to be just as reliable and
      sensitive.

PMID- 9530559
TI  - Three-dimensional structure of a human Fab with high affinity for tetanus toxoid.
AB  - BACKGROUND: The wide range of antibody specificity and affinity results from the
      differing shapes and chemical compositions of their binding sites. These shapes
      range from discrete grooves in antibodies elicited by linear oligomers of
      nucleotides and carbohydrates to shallow depressions or flat surfaces for
      accommodation of proteins, peptides and large organic compounds. OBJECTIVES: To
      determine the Fab structure of a high-affinity human antitoxin antibody. To
      explore structural features which enable the antibody to bind to intact tetanus
      toxoid, peptides derived from the sequence of the natural immunogen and antigenic
      mimics identified by combinatorial chemistry. To explain why this Fab shows a
      remarkable tendency to produce crystals consistently diffracting to d spacings of
      1.7-1.8 A. To use this information to engineer a strong tendency to crystallize
      into the design of other Fabs. STUDY DESIGN: The protein was crystallized in
      hanging or sitting drops by a microseeding technique in polyethylene glycol (PEG)
      8000. Crystals were subjected to X-ray analysis and the three-dimensional
      structure of the Fab was determined by the molecular replacement method.
      Interactive computer graphics were employed to fit models to electron density
      maps, survey the structure in multiple views and discover the crystal packing
      motif of the protein. RESULTS: Exceptionally large single crystals of this
      protein have been obtained, one measuring 5 x 3 x 2 mm (l x w x d). The latter
      was cut into six irregular pieces, each retaining the features of the original in
      diffracting to high resolution (1.8 A) with little decay in the X-ray beam. In an
      individual Fab, the active site is relatively flat and it seems likely that the
      protein antigen and derivative peptides are tightly held on the outer surface
      without significant penetration into the interior. There is no free space to
      accommodate even a dipeptide between VH and VL. One of the unique features of the
      B7-15A2 Fab is a large aliphatic ridge dominating the center of the active site.
      The CDR3 of the H chain contributes significantly to this ridge, as well as to
      adjoining regions projected to be important for the docking of the antigen. Both
      the ease of crystallization and the favorable diffraction properties are mainly
      attributable to the tight packing of the protein molecules in the crystal
      lattice. DISCUSSION: The B7-15A2 active site provides a stable and well defined
      platform for high affinity docking of proteins, peptides and their mimotopes. The
      advantages for future developments are suggested by the analysis of the crystal
      properties. It should be possible to incorporate the features promoting
      crystallization, close packing and resistance to radiation damage into engineered
      human antibodies without altering the desired specificities and affinities of
      their active sites.

PMID- 9530560
TI  - A definitive set of oligonucleotide primers for amplifying human V regions.
AB  - BACKGROUND: The creation of large diverse phage antibody libraries from natural
      sources relies on primers which are able to amplify as many V genes as possible.
      All functional germline V genes have recently been catalogued in a database, V
      BASE [1]. Previously published primer sets are unable to recognise all these V
      genes. OBJECTIVES: The design of a human primer set able to recognise all
      functional human V genes which can be used to create diverse phage antibody
      libraries. STUDY DESIGN: A new set of primers able to recognise all functional V
      genes were designed using the following criteria: at least 16 bp homology of the
      3' end of the primer to the V gene, no more than 8-fold total degeneracy and
      minimum primer dimer formation. These primers were tested in all possible
      combinations in PCR using cDNA from human peripheral blood lymphocytes or from
      human cord blood lymphocytes. RESULTS: By computer analysis, all V genes in V
      BASE could be amplified using this primer set. This theoretical result was tested
      practically by PCR and all primer pairs were shown to be functional, producing
      PCR products of the expected size. The intensity of the PCR products reflected
      information available on the expression of the different V gene families
      recognised and their expression in these two different V gene sources.
      CONCLUSIONS: This new primer set will facilitate the creation of more diverse
      phage antibody libraries than has been hitherto possible using presently
      available primer sets.

PMID- 9530562
TI  - Pathfinder selection: in situ isolation of novel antibodies.
AB  - BACKGROUND: To devise a novel method for targeted recovery of binding molecules
      from phage libraries. OBJECTIVES: To assess the potential of the novel technique
      to the selection of human antibodies to specific cell surface antigens in situ,
      including carcinoembryonic antigen (CEA), E- and P-selectins, and to the
      selection of novel antibodies which recognize immobilized purified antigen. STUDY
      DESIGN: Recovery of these antibodies from a naive human scFv library was effected
      using a 'pathfinder' molecule. Monoclonal and polyclonal antibodies, as well as
      natural ligands can serve as pathfinders when conjugated directly or indirectly
      to horseradish peroxidase (HRP). In the presence of biotin tyramine these
      molecules catalyze biotinylation of phage binding in close proximity to the
      target antigen, allowing specific recovery of 'tagged' phage from the total
      population using streptavidin. In this way, phage binding to the target itself,
      or in its immediate proximity, are selectively recovered. RESULTS: This work
      demonstrates that an existing binding specificity can be used as a tool to select
      phage libraries in situ, obviating the need to purify or clone the target.
      CONCLUSION: The speed and technical simplicity of this method should find a wide
      range of applications to phage display libraries, and could be applied to the
      discovery of new receptors and the elucidation of protein-protein interactions.

PMID- 9530561
TI  - Guided selection of antibody fragments specific for human interferon gamma
      receptor 1 from a human VH- and VL-gene repertoire.
AB  - OBJECTIVE: The guided selection strategy for isolation of human antibody (Ab)
      fragments specific for human interferon gamma receptor 1 (IFNGR-1) from a cloned
      Ab VH and VL repertoire has been investigated. In order to identify recombinant
      Abs binding to soluble antigen, a novel method termed affinity sedimentation was
      introduced here. RESULTS AND CONCLUSIONS: The VH region of murine monoclonal Ab
      (IR gamma-1) against human IFNGR-1 was combined with human VL repertoire and used
      for selection of human VL regions. One of these human VL regions (kappa 2)
      possesses high homology to the murine template VL region, also in CDR3 (77%). A
      chimeric Fab consisting of kappa 2 and the murine IR gamma-1 VH region was highly
      IFNGR-1 specific and exerted the same epitope specificity and a comparable
      binding affinity as the parental murine Fab. In a further step, the selected
      human VL region kappa 2 was combined with a human VH repertoire and led by guided
      selection to the generation of a completely human Fab (1b5) specific for human
      IFNGR-1. The overall VH region homology of 1b5 compared to the parental antibody
      IR gamma-1 was 81%, with a rather low homology in CDR3. Binding competition
      studies revealed that the epitope recognized by 1b5 differs from the parental Ab
      IR gamma-1.

PMID- 9530563
TI  - Therapeutic antibody technology 97.
AB  - Almost 200 antibody aficionados attended the Therapeutic Antibody Technology 97
      meeting, held September 21-24, 1997 at the Holiday Inn, Union Square in the heart
      of San Francisco, CA. The meeting was sponsored by the Palo Alto Institute of
      Molecular Medicine and organized by James W. Larrick (PAIMM) and Dennis R. Burton
      (Scripps Research Institute). The meeting featured excellent discussions on many
      interesting talks and a number of poster presentations. It is likely that another
      meeting will be organized in 2 years, however in the meantime, an effort is
      underway to organize a 'Virtual Antibody Society' to be set up on the web server
      at Scripps Research Institute in La Jolla, CA (Questions and comments on this
      project can be sent to: Jwlarrick@aol.com or Burton@scripps.edu). Richard Lerner
      (Scripps) gave the keynote address on 'Catalytic Antibodies', describing recent
      work with Carlos Barbas on so-called reactive immunization to generate a high
      activity aldolase catalytic antibody. This antibody, soon to be described in an
      article in Science, is the first commercially available catalytic antibody.

PMID- 9530564
TI  - Progress in programming antibody fragments to crystallize.
AB  - Completion of the X-ray analysis of the human B7-15A2 Fab opened a new vista
      (Immunotechnology 3, no. 4). In the crystal lattice, both the lambda-type light
      chain (CL domain) and gamma 1-type heavy chain (CH1 domain) participated in
      formation of antiparallel beta-pleated sheets with neighboring molecules related
      to the reference Fab by 2-fold axes. This observation evoked memories of the
      first description of this type of packing for human Bence-Jones (lambda chain)
      dimers 20 years ago (Ely K.R. et al. Biochemistry 1978;17:158-167). Reexamination
      of packing interactions in selected crystal systems revealed that the C domains
      of lambda and gamma 1 chains were structurally amenable to the formation of such
      cross-molecule beta-structures, but kappa chain CL domains were not. In the
      latter, a single proline residue disrupted the order of beta-strand 3-3 in the
      middle of the surface used in lambda and gamma 1 chains for intermolecular
      interactions with symmetry-related molecules. For the packing of Fv molecules,
      the VL domains are structurally well suited for analogous packing interactions
      through antiparallel 4-1 beta-strands in adjacent molecules. Such interactions
      have been shown to provide the driving force in the crystal packing of a human
      (Pot) Fv from an IgM-kappa cryoglobulin. Together, these observations suggest
      several avenues through which propensity to crystallize can be programmed into
      the designs of synthetic human Fabs, Fvs and single-chain antibodies.

PMID- 9530565
TI  - [Pathophysiology, epidemiology and complications of atrial fibrillation].

PMID- 9530566
TI  - [Paroxysmal supraventricular tachycardia. Diagnostic methods].

PMID- 9530567
TI  - [Drug therapy and prevention of recurrence of supraventricular tachyarrhythmias].

PMID- 9530569
TI  - [Anticoagulation in supraventricular tachyarrhythmias. Clinical value and
      therapeutic risk].

PMID- 9530568
TI  - [Supraventricular tachyarrhythmias. Cardiac, extra-cardiac and arrhythmogenic
      side effects of anti-arrhythmia drugs].

PMID- 9530570
TI  - [Electrotherapy of supraventricular tachyarrhythmias. External versus internal
      defibrillation].

PMID- 9530571
TI  - [Catheter ablation procedures in supraventricular tachycardia].

PMID- 9530572
TI  - [Paraneoplastic syndromes].

PMID- 9530573
TI  - [Coronary aneurysms as the cause of acute myocardial infarct in a 28-year-old
      high performance athlete].

PMID- 9530574
TI  - [56-year-old man with acrocyanosis, livedo reticularis, renal failure and
      arterial hypertension. Cholesterol embolism syndrome (CES)].

PMID- 9530575
TI  - [Why do hemophiliacs bleed?].

PMID- 9530576
TI  - [How does Bulau drainage work?].

PMID- 9530577
TI  - [Clinical relevance of so-called latent sprue].

PMID- 9530578
TI  - [Definition of an immunologic deficiency state].

PMID- 9530579
TI  - [Interferons and nucleoside analogs. New perspectives in therapy of chronic viral
      hepatitis].

PMID- 9530580
TI  - The anterior capsulotomy revisited.

PMID- 9530581
TI  - Intraocular pressure measurement following hyperopic LASIK.

PMID- 9530582
TI  - Viscoelastic purity.

PMID- 9530583
TI  - Importance of postoperative evaluation in surgery.

PMID- 9530584
TI  - Bevel-down phaco.

PMID- 9530585
TI  - Patient selection for phacoemulsification by residents in underdeveloped
      countries.

PMID- 9530586
TI  - Consultation section. Cataract surgical problem.

PMID- 9530588
TI  - Step-by-step chop in situ and separation of very dense cataracts.

PMID- 9530587
TI  - Removal of flap striae following laser in situ keratomileusis.
AB  - While laser in situ keratomileusis (LASIK) offers advantages over photorefractive
      keratectomy (PRK), creation of the corneal flap has been associated with
      postoperative flap striae. These result from misalignment of the corneal flap
      after flap replacement, movement of the corneal flap during the first
      postoperative day, or the "tenting effect" of the corneal flap over the ablated
      stromal bed. Flap striae become more difficult to remove as the postoperative
      course progresses; therefore, identifying the striae on the first postoperative
      day is imperative. We describe techniques of flap hydration, refloating,
      stretching, and smoothing that we use to remove visually significant flap striae.

PMID- 9530589
TI  - Nucleus fragmentation in a scleral pocket for small incision extracapsular
      cataract extraction.
AB  - We present a technique for planned manual extracapsular cataract extraction
      (ECCE) incorporating a modification of mini-nuc ECCE in which the scleral tunnel
      is made wide enough to allow a nucleus of any size to settle in the tunnel. A 5.0
      mm, inverted-V chevron incision is used in which the exposed part of the nucleus
      lodged in the scleral pocket can be manually picked and fragmented until it is
      small enough to be removed through the incision. The chevron incision is flexible
      enough to allow a medium-sized nucleus to be extracted without fragmentation and
      implantation of a rigid 6.0 mm poly(methyl methacrylate) lens. Vector analysis of
      preoperative and 3 month postoperative keratometric results in 30 patients showed
      that the surgically induced vector was 0.54 diopter (D) +/- 0.58 (SD). Mean
      reduction in astigmatism was 0.08 +/- 0.39 D. The sutureless technique is fast
      and safe, allows a nucleus of any size to be extracted through a constant size
      5.0 mm incision, and results in minimal postoperative astigmatism.

PMID- 9530590
TI  - Laser in situ keratomileusis assisted by corneal topography.
AB  - PURPOSE: To assess whether laser in situ keratomileusis (LASIK) assisted by
      corneal topography can successfully treat corneal irregularities or irregular
      astigmatism in patients with previous ocular surgery or ocular trauma. SETTING:
      University Eye Hospital, Klinikum Mannheim, Mannheim, Germany. METHODS: In a
      prospective clinical study, LASIK was performed in 23 eyes of 22 patients.
      Reasons for surgery were irregular astigmatism after penetrating keratoplasty or
      penetrating injury or corneal irregularity after previous excimer laser surgery.
      Excimer ablation was based on preoperative corneal topography data (Corneal
      Analysis System, EyeSys Technologies) using a proprietary algorithm (Topographic
      Assist LASIK, Chiron Vision). Follow-up was 6 months. RESULTS: Mean preoperative
      uncorrected visual acuity (UCVA) was 20/80 and mean best spectacle-corrected
      visual acuity (BSCVA), 20/35. Uncorrected visual acuity improved in all but two
      cases. Postoperatively, mean UCVA increased to 20/50; mean BSCVA was unchanged.
      No eye lost two or more lines of BSCVA. Postoperative topography showed less
      corneal irregularity in 81.3% of eyes; full correction was achieved in 19.4%.
      Four eyes (19.4%) needed re-treatment for undercorrection and three eyes (14.3%)
      for regression. CONCLUSION: Preliminary results indicate that the concept of
      topographic-assisted LASIK is feasible. However, most eyes were undercorrected
      and had regression. One reason might be that corneal topography underestimated
      corneal irregularity, causing significant undercorrection.

PMID- 9530591
TI  - Laser in situ keratomileusis for myopia and myopic astigmatism.
AB  - PURPOSE: To evaluate the precision and safety of myopia and astigmatism
      correction using laser in situ keratomileusis (LASIK). SETTING: Augenchirurgie
      und Laserzentrum Hoch-Rum (Sanatorium der Kreuzsch-western), Innsbruck, Austria.
      METHODS: In this prospective study, LASIK was performed on 66 eyes of 39 patients
      with myopia ranging from 1.50 to 16.00 diopters (D). Astigmatism, ranging from 
      0.00 to -3.00 D, was treated simultaneously. Surgery was performed with the
      Chiron Keracor 117 excimer laser and the Chiron Automated Corneal Shaper
      microkeratome. During the 6 month follow-up, manifest refraction as well as best
      corrected and uncorrected visual acuities were measured; corneal topographies
      were produced and slitlamp biomicroscopy was performed. Changes in visual acuity
      and corneal topography were evaluated. RESULTS: After 6 months, mean myopia had
      decreased from 6.78 D +/- 3.48 (SD) to 0.40 +/- 0.98 D. Fifty-one of 63 eyes
      (81.0%) were within +/- 1.00 D of spherical emmetropia and 61 of 63 (96.8%)
      within +/- 1.00 D of cylindrical emmetropia. Uncorrected visual acuity improved
      in all eyes; it was 20/40 or better in 82.5% 6 months postoperatively. Best
      corrected visual acuity did not change in most eyes; 9.5% lost two or more
      Snellen lines. No central islands or corneal scars were detected postoperatively.
      Haze was noted in only 6 eyes (9.1%); it was transient and less than grade 1. No
      sight-threatening complications occurred intraoperatively. CONCLUSION: Laser in
      situ keratomileusis was an exact and predictable procedure for correcting low,
      moderate, and high myopia and myopic astigmatism.

PMID- 9530592
TI  - Contrast sensitivity after laser in situ keratomileusis.
AB  - PURPOSE: To evaluate the effect on contrast sensitivity function of laser in situ
      keratomileusis (LASIK) for the correction of myopia. SETTING: Alicante Institute
      of Ophthalmology, University of Alicante, Spain. METHODS: Fourteen eyes of 10
      patients had LASIK to correct myopia ranging from 6.00 to 19.50 diopters (D).
      Mean preoperative myopia was 10.39 D +/- 3.69 (SD). Contrast sensitivity was
      tested preoperatively and 1, 3, and 6 months postoperatively using the CVS-1000E
      contrast sensitivity unit (VectorVision). RESULTS: Contrast sensitivity decreased
      1 month postoperatively; the decrease was significant only at the low and
      intermediate spatial frequencies of 3 and 6 cycles per degree (cpd) (P = .034 and
      .030, respectively). Starting from the first month, there was rapid recovery of
      contrast sensitivity and at the third month, no statistically significant
      decrease at all spatial frequencies. Six months after surgery, there was an
      increase in contrast sensitivity values at 3, 12, and 18 cpd, although the
      changes were not significant. CONCLUSION: Although LASIK decreased contrast
      sensitivity values at low and intermediate spatial frequencies for 1 month after
      surgery, these values rapidly returned to the preoperative values at 3 months.
      The improvement at certain frequencies at 6 months suggests that LASIK can
      improve the quality of vision in eyes with moderate and high myopia.

PMID- 9530593
TI  - Mathematics of laser in situ keratomileusis for high myopia.
AB  - PURPOSE: To determine the maximal ablation that can be safely performed with
      laser in situ keratomileusis (LASIK) to maintain long-term corneal integrity.
      SETTING: TLC The Windsor Laser Center, Windsor, Canada. METHODS: The pretreatment
      protocols for the VISX Star, Summit Omnimed, and Chiron Technolas 116 excimer
      lasers generally apply 1 to 2 microns per diopter (D) at an optical zone of 3.0
      mm or less to avoid the postoperative central islands that can occur with broad
      beam excimer lasers. The ablation depth per diopter for the VISX Star, Summit
      Omnimed, Chiron Technolas 116, and Chiron Technolas 217 excimer lasers ranges
      from 10 to 24 microns per diopter depending on the size and number of ablation
      zones and the excimer laser used. RESULTS: Previous experience with lamellar
      surgery suggests that at least 250 microns of central posterior stromal tissue
      should be preserved to maintain long-term corneal integrity and avoid
      postoperative corneal ectasia. If a 160 microns flap is created for LASIK, the
      average 550 microns cornea will have 140 microns of corneal stroma available for
      ablation. Depending on the excimer laser and ablation nomogram used, the maximal
      LASIK correction for the average cornea ranges from 9.8 to 15.0 D. CONCLUSION:
      The preoperative corneal thickness and the depth of the excimer laser ablation
      must be evaluated before LASIK to ensure that adequate posterior corneal stroma
      is preserved.

PMID- 9530594
TI  - Accuracy of ultrasonic pachymetry and videokeratography in detecting keratoconus.
AB  - PURPOSE: To compare the accuracy of ultrasonic pachymetry measurements and
      videokeratography-derived indices in distinguishing keratoconus patients from
      those with normal eyes. SETTING: A subspecialty cornea practice (Los Angeles,
      California, USA) and the Keratoconus Genetics Research Project. METHODS: Corneal
      thickness was measured by ultrasonic pachymetry at the center and inferior
      margins of the pupil of 142 normal and 99 keratoconus patients The corneal
      surface topography of patients was studied with the Topographic Modeling System
      (TMS-1). The videokeratographs obtained were analyzed with a computer program
      that automatically calculates two indices derived from data points in the central
      and paracentral cornea: central K and I-S values. Linear discriminant analysis
      was used to determine the correct classification percentages using pachymetry
      measurements and indices derived from videokeratography as the independent
      variables. RESULTS: The range of corneal thickness in normal and keratoconic eyes
      overlapped considerably. In the discriminant analysis, videokeratography indices
      provided a 97.5% correct classification rate and pachymetry data, an 86.0% rate
      (P < .01, McNemar's test). CONCLUSION: Keratoconus is more accurately
      distinguished from the normal population by videokeratography-derived indices
      than by ultrasonic pachymetry measurements. This may be due to the large
      variation in corneal thickness in the normal population or the inability of
      ultrasonic pachymetry to accurately detect the location of corneal thinning in
      keratoconus by measuring standard points on the cornea. Pachymetry should not be
      relied on to exclude or diagnose keratoconus because the false-negative and false
      positive rates are unacceptably higher than those obtained by videokeratography.

PMID- 9530595
TI  - Keratometric index, videokeratography, and refractive surgery.
AB  - PURPOSE: To clarify the confusion resulting from the use of slightly different
      refractive indices in calculations related to optical modeling of the cornea for
      refractive surgery, corneal diagnostics, and cataract surgery. SETTING:
      Scientific Institute H.S. Raffaele, Milan, Italy. METHODS: The cornea is
      represented as a centered optical system composed by 1, 2, or 3 spherical
      interfaces, in progression of modeling accuracy. Optical analysis is performed
      with the usual formulas of paraxial geometrical optics as well as with ray
      tracing. Simple models are also provided for corneas having both incisional and
      photoablative refractive surgery. Values of geometrical parameters are taken from
      the Gullstrand eye model. RESULTS: Using the keratometric index of refraction of
      1.3375 is validated for estimating optical power differences on untreated corneas
      or after incisional keratotomy. It is not as accurate in assigning absolute
      values of dioptric power, where the value 1.3315 is more appropriate. For
      photorefractive keratectomy (PRK), however, the proper stromal index of
      refraction, 1.376, must be used for ablation calculations and dioptric change
      estimates. CONCLUSION: Videokeratographic instruments should include three
      distinct values of refraction index (1.3375, 1.376, and 1.3315) for an accurate
      and complete characterization of dioptric power maps. In cataract surgery,
      corrections must be introduced in the calculation of intraocular lens power for
      patients who have previously had PRK.

PMID- 9530596
TI  - Outcomes of small incision cataract surgery.
AB  - PURPOSE: To compare cataract surgery outcome measures 4 months postoperatively
      and determine their association with changes in the eye's functional state.
      SETTING: Department of Ophthalmology, Helsinki University Central Hospital,
      Finland. METHODS: This longitudinal study comprised 219 consecutive patients
      having first-eye or second-eye cataract surgery by one surgeon. In most patients,
      the technique consisted of small-incision cataract surgery with in-the-bag
      intraocular lens implantation. Patients were interviewed and clinical data
      obtained preoperatively and 4 months postoperatively. Adverse events occurring
      within 24 hours and 4 months postoperatively were compared with changes in global
      measures of vision. Surgical success in terms of surgically induced astigmatism
      (SIA) was measured at 4 months using vector analysis of the changes in
      astigmatism and defining the extent to which the surgical goal was achieved. The
      association between the surgical astigmatism goals and global measures of vision
      was analyzed. RESULTS: The percentage of patients showing improvement 4 months
      after first-eye cataract surgery varied by outcome measure: Snellen visual acuity
      (95.0%), VF-14 score (89.4%), satisfaction with vision (80.1%), self-reported
      trouble with vision (75.8%), and cataract symptoms (75.1%). Changes in Snellen
      acuity after second-eye cataract surgery were similar but VF-14 changes were
      significantly less than after first-eye surgery. Changes in global measures of
      vision were also better after first-eye surgery. The correlation between the
      change in VF-14 score and global measures of vision was stronger than between the
      change in Snellen acuity and the same general outcome measures. A good
      correlation was also seen between the changes in VF-14 scores and cataract
      symptoms. Mean SIA in all eyes was 0.2 diopter (D) +/- 0.7 (SD); 91.2% were
      within +/- 1.0 D of preoperative values. Failure to achieve surgical astigmatism
      goals was not associated with patients in whom global measures of vision did not
      improve, nor was there a correlation between adverse events occurring within 24
      hours or 4 months postoperatively and global measures of vision. The only
      association was between ocular comorbidity or potential risk factors of
      phacoemulsification and adverse events seen within 24 hours and at 4 months.
      CONCLUSION: Estimates of the proportion of patients benefiting from cataract
      surgery varied with the outcome measure used to determine benefit. The change in
      the VF-14 score was a better measure than Snellen acuity of the benefit of
      cataract surgery.

PMID- 9530597
TI  - Vision-specific function and quality of life after cataract extraction in south
      India.
AB  - PURPOSE: To assess visual and overall patient function after intracapsular (ICCE)
      and extracapsular (ECCE) cataract extraction in rural South India. SETTING:
      Aravind Eye Hospital, Tirunelveli, Tamil Nadu, South India, and the Dana Center
      for Preventive Ophthalmology, Wilmer Eye Institute, Baltimore, Maryland, USA.
      METHODS: This study evaluated preoperative visual acuity and demographic
      information and postoperative visual acuity and functional status measures in 71
      patients having ECCE with posterior chamber intraocular lens (IOL) placement and
      73 patients having ICCE with aphakic spectacle correction at Aravind-Tirunelveli
      Eye Hospital, Tamil Nadu, India. The principal outcomes assessed were visual
      acuity; quality-of-life score (possible range 0 to 100%); visual function
      measurement (possible range 0 to 100%). RESULTS: Patients in the ECCE group
      scored 10.17 (P = .0001) points higher than those in the ICCE group on the visual
      function scale after adjustment for differences in age, sex, level of education,
      marital status, residence, and type of employment. The ECCE group scored 7.69
      points higher on visual function when adjusting for the differences in best
      corrected visual acuity, which was also better in the ECCE group. In the quality
      of-life assessment, 77.1% in the ECCE group and 46.6% in the ICCE group scored
      90% or better (OR 3.85; P = .006). CONCLUSIONS: Patients in rural south India
      having ECCE with posterior chamber IOL implantation obtained better postoperative
      visual function, quality of life, and visual acuity than those receiving ICCE
      with aphakic spectacle correction. These differences, which were not
      significantly affected by adjustment for age, sex, education, marital status,
      type of residence, and occupation, indicate that ECCE is clearly superior to
      ICCE.

PMID- 9530598
TI  - Phacoemulsification and lens implantation in rabbit eyes: capsular bag versus
      ciliary sulcus implantation and 4.0 versus 7.0 mm capsulorhexis.
AB  - PURPOSE: To compare the effects of intraocular lens (IOL) implantation in the
      capsular bag versus the ciliary sulcus and of a 4.0 versus 7.0 mm continuous
      curvilinear capsulorhexis (CCC) on postoperative inflammation and after-cataract
      formation. SETTING: St. Erik's Eye Hospital, Karolinska Institute, Stockholm,
      Sweden. METHODS: Trial 1 comprised 40 rabbits that had CCC, endocapsular
      phacoemulsification, and a poly(methyl methacrylate) IOL implanted in the
      capsular bag in one eye and the ciliary sulcus in the fellow eye. In Trial 2, 40
      rabbits had a 4.0 mm CCC in one eye and a 7.0 mm CCC in the fellow eye followed
      by phacoemulsification and IOL implantation in the capsular bag. White blood cell
      (WBC) counts and prostaglandin E2 (PGE2) concentrations in aqueous humor were
      determined at 1, 3, 7(8), 28, and 56 days postoperatively. Wet mass of the
      dissected after-cataract was measured at day 56. In Trial 1, wet mass of the iris
      ciliary body was measured at each observation. RESULTS: In Trial 1, WBC counts at
      day 1 were higher with a sulcus-fixated IOL (P = .05). The median wet mass of the
      dissected after-cataract was 108.5 mg in eyes with a sulcus-fixated IOL and 62.5
      mg in eyes with a capsule-fixated IOL (P = .01). In Trial 2, WBC counts at day 8
      were significantly higher in eyes with a 7.0 mm CCC than in those with a 4.0 mm
      CCC (P < .05). There was no significant difference in the amount of after
      cataract. CONCLUSIONS: The results indicate that IOL implantation in the capsular
      bag causes less inflammation and after-cataract formation than sulcus fixation
      and that using a large CCC does not affect the total amount of after-cataract but
      may enhance the inflammatory response.

PMID- 9530599
TI  - Effect of heparin in irrigating solution on inflammation following small incision
      cataract surgery.
AB  - PURPOSE: To study the effect of heparin-sodium added to the irrigating solution
      on postoperative inflammation in patients having cataract surgery. SETTING:
      Department of Ophthalmology, University of Giessen, Giessen, Germany. METHODS:
      Seventy-two patients having phacoemulsification with posterior chamber
      intraocular lens (IOL) implantation were randomly assigned to receive regular
      irrigating solution or solution with heparin-sodium (final diluted concentration
      10 IU/mL). In half the patients, poly(methyl methacrylate) (PMMA) IOLs were
      implanted and in half, foldable silicone IOLs. The patients were examined
      preoperatively, on days 1 and 3, and 1 year postoperatively. Postoperative
      inflammation was objectively evaluated by measurement of flare and cells using
      laser flare-cell photometry. RESULTS: The mean postoperative flare values were
      significantly lower in the groups with additional heparin-sodium at days 1 and 3
      (P < . 01). Flare values were not significantly different 1 year postoperatively.
      Cell values for the heparin-treated groups were lower, but the difference did not
      reach statistical significance. Flare and cells values for the two IOL materials
      were not significantly different during the entire follow-up. CONCLUSION: Heparin
      sodium added to the infusion solution during small incision cataract surgery
      reduced inflammation in the early postoperative period.

PMID- 9530600
TI  - Spatial resolution threshold in pseudophakic patients with monofocal and
      multifocal intraocular lenses.
AB  - PURPOSE: To compare the spatial resolution threshold in the central visual field
      of pseudophakic patients with monofocal and multifocal intraocular lenses (IOLs).
      SETTING: Eye Clinic, University of Trieste, Italy. METHODS: Twenty phakic normal
      subjects and four groups of 20 pseudophakic patients each, implanted with
      refractive and diffractive multifocal IOLs (Domilens Progress 1, AMO Array
      MPC25NB, or Pharmacia 811X) or with monofocal IOLs (Allergan PC43NB), were
      studied. The spatial resolution threshold in the central visual field was
      assessed using high-pass resolution perimetry. Measurements were performed adding
      spherical correction to test the different foci of the IOL. RESULTS: No
      significant differences between phakic subjects and pseudophakic patients with
      monofocal IOLs were found. In distance vision, no significant differences between
      patients with refractive multifocal IOLs and those with monofocal IOLs were
      found. The group with the diffractive multifocal IOL showed a significantly
      higher spatial resolution threshold (P = .003). In intermediate vision, the AMO
      Array group showed a significantly lower spatial resolution threshold than the
      other groups (P < .01). The best performance at near distance was in the
      diffractive group, which was statistically significantly different from the other
      groups (P < .001). CONCLUSION: In the diffractive group, the high spatial
      resolution threshold in distance vision could be explained by the lower
      brightness of the principal focus, related to a different light energy division
      between the foci. In the Domilens group, the high spatial resolution threshold in
      near vision could be related to the light energy scattered in a large number of
      foci.

PMID- 9530601
TI  - Long-term intraocular pressure control after cataract extraction with
      trabeculectomy: phacoemulsification versus extracapsular technique.
AB  - PURPOSE: To compare long-term intraocular pressure (IOP) control after
      extracapsular cataract extraction and intraocular lens (IOL) implantation
      combined with trabeculectomy (ECCE + TRAB) with that after phacotrabeculectomy
      and IOL implantation. SETTING: Glaucoma Unit, Royal Liverpool University
      Hospital, Liverpool, England. METHOD: This retrospective study comprised 32 eyes
      having ECCE + TRAB and 31 eyes having phacotrabeculectomy with a mean follow-up
      of 37.5 and 41.0 months, respectively. The need for pressure-lowering medication
      was recorded. Kaplan-Meier curves were created for each group. RESULTS: At every
      measurement after 3 weeks of follow-up, significantly fewer eyes in the
      phacotrabeculectomy group required IOP-lowering medication (P = .04).
      CONCLUSIONS: After both ECCE + TRAB and phacotrabeculectomy, IOP control was
      achieved in significantly more eyes on fewer pressure-lowering medications than
      preoperatively. Phacotrabeculectomy with IOL implantation led to better unaided
      long-term postoperative IOP control than ECCE + TRAB with IOL implantation.

PMID- 9530602
TI  - Intraocular pressure change after sutureless phacoemulsification and foldable
      posterior chamber lens implantation.
AB  - PURPOSE: To investigate the effect on intraocular pressure (IOP) of sutureless
      scleral and corneal tunnel Kelman phacoemulsification (KPE) with foldable
      posterior chamber intraocular lens (IOL) implantation. SETTING: Jules Stein Eye
      Institute, Los Angeles, California, USA. METHODS: Preoperative and postoperative
      (1 and 6 weeks and 6 to 8 months) IOP measurements of 385 consecutive eyes having
      uneventful phacoemulsification and foldable posterior chamber IOL implantation
      were reviewed retrospectively. A subset of 193 eyes for which no IOP measurements
      were missing at any follow-up were analyzed separately. RESULTS: Mean
      preoperative IOP was 15.8 mm Hg +/- 0.2 (+/- SE). It dropped postoperatively by
      1.3 +/- 0.2 mm Hg at 1 week (P < .001), 2.5 +/- 0.2 mm Hg at 6 weeks (P < .001),
      and 2.2 +/- 0.2 mm Hg at 6 to 8 months (P < .001). Mean preoperative IOP for the
      subset without missing data was 16.0 +/- 0.3 mm Hg. It decreased by 1.1 +/- 0.3
      mm Hg at 1 week (P < .001), 2.3 +/- 0.2 mm Hg at 6 weeks (P < .001), and 2.2 +/-
      0.2 mm Hg at 6 to 8 months (P < .001). Wound construction (scleral versus corneal
      tunnel), anesthesia type (topical versus posterior orbital injection), the eye
      operated on, and patient age and sex did not significantly influence the
      postoperative pressure change. Patients with a preoperative diagnosis of glaucoma
      had significantly higher 1 week postoperative IOPs; however, the differences were
      statistically insignificant at 6 weeks and 6 to 8 months. CONCLUSION: Sutureless
      KPE with foldable posterior chamber IOL implantation lowered IOP by 1.1 to 2.5 mm
      Hg for the 6 months immediately following surgery. Glaucoma patients had a
      statistically significant initial rise in IOP at 1 week.

PMID- 9530603
TI  - Potential acuity meter versus scanning laser ophthalmoscope to predict visual
      acuity in cataract patients.
AB  - PURPOSE: To compare the relative abilities of the Potential Acuity Meter (PAM)
      and the Scanning Laser Ophthalmoscope (SLO) to predict the postoperative visual
      acuity in patients with mild to dense cataract. SETTING: Gimbel Eye Centre,
      Calgary, Alberta, Canada. METHODS: In this single-masked prospective study of 31
      consecutive eyes with mild to dense cataract and a best corrected visual acuity
      (BCVA) of 20/40 or less, patients had predictive visual acuity (PVA) testing
      using the PAM and SLO. Preoperative and postoperative BCVA was recorded using
      Snellen charts. Differences between PVA and postoperative BCVA results were
      assessed by a two-tailed t-test and correlation analysis. RESULTS: The SLO was
      correct within two lines of outcome in 30 of 31 eyes and the PAM, in 19 of 31
      eyes. A two-tailed dependent t-test showed a significant difference between
      predicted and final visual acuity for the PAM (P = .0001) and a nonsignificant
      difference for the predicted and final visual acuity for the SLO. A correlation
      analysis showed a mild correlation for the PAM (r = .49) and a good correlation
      for the SLO (r = .81). For a prediction of better or worse than 20/40, the SLO
      showed a sensitivity of 0.964 and specificity of 1.0 and the PAM, of 0.67 and
      1.0, respectively. CONCLUSION: The SLO was more accurate than the PAM in
      predicting visual acuity after cataract surgery. The relative cost of the SLO is
      potentially restrictive to its widespread clinical application. However, the
      cost/benefit in terms of patient satisfaction with predictable surgical results
      should be considered.

PMID- 9530604
TI  - Phacoemulsification of white mature cataracts.
AB  - PURPOSE: To evaluate the intraoperative difficulties associated with
      phacoemulsification of white mature cataracts and develop a strategy for
      consistently achieving continuous curvilinear capsulorhexis (CCC) in these cases.
      SETTING: Raghudeep Eye Clinic, Iladevi Cataract & IOL Research Centre, Ahmedabad,
      India. METHODS: This prospective study comprised 60 eyes of 60 patients with
      senile white mature cataract. Mean follow-up was 7 months. Detailed preoperative
      and intraoperative notes were made including intraoperative subjective assessment
      of the intracapsular pressure and cataract hardness. A small capsulorhexis was
      attempted initially. Endophacoemulsification was performed using the stop, chop,
      chop, and stuff technique. The capsulorhexis was enlarged before intraocular lens
      implantation. An initial cut in the capsulorhexis margin was made with a
      cystotome needle while a spatula supported the anterior capsule. The
      capsulorhexis was then enlarged with forceps. RESULTS: A CCC was achieved in 57
      eyes (95%). Intracapsular pressure was judged to be raised in 24 eyes (40%). Of
      these, CCC was accomplished in 21 eyes (88%). Statistical analysis confirmed that
      raised intracapsular pressure was a significant factor. Capsule opacification or
      plaque was detected at the end of the surgery in 20 eyes (33%); 50% of the nuclei
      were of grade 5 hardness. CONCLUSION: If a CCC can be achieved, the results of
      white cataract phacoemulsification are comparable to those of routine cataract
      surgery. When using the two-stage technique, one should be prepared to deal with
      a hard cataract through a small capsulorhexis.

PMID- 9530605
TI  - Dehiscence of a radial keratotomy incision during clear corneal cataract surgery.
AB  - We report a case of dehiscence of a radial keratotomy (RK) incision caused by
      clear corneal cataract surgery. The patient had eight-incision RK in both eyes 9
      months previously with enhancement surgery in the left eye 1 month later.
      Cataract surgery through a clear corneal incision was performed in the right eye
      and 1 month later, in the left. Surgery in the right eye was uneventful. However,
      during surgery in the left eye, dehiscence of one radial incision occurred. The
      wound dehiscence was closed with interrupted sutures, and the patient achieved
      20/20, uncorrected visual acuity 1 week after surgery.

PMID- 9530606
TI  - Secondary implantation of a double intraocular lens after penetrating
      keratoplasty.
AB  - Penetrating keratoplasty (PKP) patients often have severe, visually disabling
      refractive errors. Astigmatism can be addressed by refractive surgery; however,
      correcting hyperopia is more problematic. Although pseudophakic PKP patients can
      have a lens exchange, it can be traumatic in this population. In this
      pseudophakic PKP patient, I added a second posterior chamber intraocular lens,
      correcting the hyperopia and resolving visual complaints.

PMID- 9530607
TI  - Posterior capsule rupture after blunt trauma.
AB  - Two patients had rupture of the posterior lens capsule caused by blunt trauma. In
      both, the typical fibrosed edges of the posterior capsule breaks were clearly
      visible and could be documented preoperatively.

PMID- 9530608
TI  - Development and evaluation of an ELISA to measure antibody responses to both the
      nucleocapsid and spike proteins of canine coronavirus.
AB  - A rapid and reproducible enzyme linked immunosorbent assay (ELISA) was developed
      for detection of canine coronavirus (CCV) specific antibodies directed to both
      the nucleocapsid (NC) and the spike (S) proteins. The coating antigen, a methanol
      treated, S-protein enriched preparation, was produced by subjecting infected
      cells to Triton X-114 detergent followed by phase separation. The sensitivity of
      this assay was determined by following the course of infection in dogs
      experimentally infected with CCV. The specificity of the antibody response was
      determined by Western blot analysis and supported the increased magnitude of the
      ELISA response and the presence of serum neutralizing (SN) antibody. Due to the
      sensitivity and specificity of the IgG response detected by this assay it can be
      used to determine both virus exposure and vaccine efficacy.

PMID- 9530609
TI  - Determination of transforming growth factor-beta 2 (TGF-beta 2) in bovine
      colostrum samples.
AB  - Transforming growth factor-beta 2 (TGF-beta 2) is the major TGF-beta form in
      bovine colostrum. A colostrum pool of the five first milkings was made to
      validate an ELISA specific for human TGF-beta 2 for measure TGF-beta 2
      concentration in bovine colostrum samples. According to this test > 90% of total
      TGF-beta 2 (74.5 +/- 4.4 ng/ml) in colostrum pool was in a latent form that could
      be activated by acetic acid treatment, whereas the concentration of the active
      form was only 4.19 +/- 0.27 ng/ml. Activated colostrum samples of the first
      milkings of five cows contained 150-1150 ng TGF-beta 2/ml and its concentration
      declined in correlation (r = 0.86) with total protein concentration to 12-71
      ng/ml by the fifth milkings. Most of the TGF-beta 2 (94%) was found in the whey
      fraction of colostrum. The ELISA results were also compared with a TGF-beta 2
      bioassay, the fibroblasts migration assay. This assay detected 9.8 +/- 1.0 ng/ml
      and 4.4 +/- 0.7 ng/ml in the activated and non-activated samples of colostrum
      pool respectively.

PMID- 9530610
TI  - Use of dried smooth lipopolysaccharide antigen coated polystyrene plates for
      diagnosis of bovine brucellosis by enzyme immunoassay.
AB  - Polystyrene plates (96 well) were sensitized with Brucella abortus smooth
      lipopolysaccharide (SLPS) antigen and then air dried at room temperature (RT) for
      about 1 hour to dry. Dryness was judged complete when a buffer meniscus was
      absent from the bottom of the well. The plates were resealed kept on the bench at
      RT for the duration of the study. Testing was done over 13 months by competitive
      and indirect ELISAs (C- and IELISA) for bovine antibody to B. abortus using
      panels of sera from B. abortus S19 vaccinated, unexposed and infected cattle.
      Testing revealed that consistent results were obtained over the test period
      suggesting that air drying may be a suitable alterative for storage of plates
      sensitized with some antigens, in particular, smooth lipopolysaccharide.

PMID- 9530611
TI  - Production and characterization of a monoclonal antibody specific for ubiquitin
      like polypeptide responsible for nonspecific immune suppression.
AB  - Monoclonal nonspecific suppressor factor (MNSF) is a lymphokine product of a
      murine T cell hybridoma that inhibits the immune response in an antigen
      nonspecific manner. Recently, we found that a novel ubiquitin-like protein (Ubi
      L), a subunit of MNSF, is responsible for its biological activity. We developed a
      monoclonal antibody with specific activity against Ubi-L. Inhibition experiments
      showed that this mAb, termed NA4, preferentially recognizes Ubi-L but not
      irrelevant proteins such as ubiquitin. With the use of NA4, we established an
      ELISA method for the quantitation of Ubi-L. By this ELISA system, approximately
      40 ng/ml of MNSF was detected in the culture supernatants of concanavalin A (Con
      A)- or interferon gamma (IFN gamma)-activated splenocytes, whereas MNSF in the
      supernatant of IFN alpha- and IFN beta-stimulated splenocytes was nil. In
      addition, NA4 could abrogate the action of Ubi-L. Thus NA4 was confirmed to be a
      pertinent tool for elucidation of the underlying mechanism of action of MNSF.

PMID- 9530612
TI  - Clinical performance of the AMDL DR-70 immunoassay kit for cancer detection.
AB  - A clinical study using DR-70 immunoassay for the detection of 13 different
      cancers have been conducted with 277 healthy subjects and 136 cancer patients.
      The test results showed that the DR-70 immunoassay kit was capable of detecting
      cancers with high degree of specificity and sensitivity. At 95% specificity
      level, the sensitivity of the assay was 87.8%, 92.6%, 65.2% and 66.7%,
      respectively for lung, stomach, breast and rectum cancers. Furthermore the test
      kits were shown to be stable and performed reproducibly.

PMID- 9530613
TI  - Composition and nutritive value of yeast biomass and yeast protein concentrates.
AB  - Yeast biomass (Saccharomyces sp.) produced in local breweries as a by-product was
      utilized in this study. Percent proximate composition, amino acid composition,
      and protein nutritive value were determined for the yeast cell biomass (YC), a
      sodium perchlorate extracted and isoelectrically precipitated protein concentrate
      (P-PC), and a sodium trimetaphosphate treated extract followed by isoelectrical
      precipitation (TMP-PC). Protein concentrates averaged 75% protein as compared to
      48.5% in the yeast biomass. Precipitation of the protein in the presence of
      either sodium perchlorate or sodium trimetaphosphate was reduced to 71% and 51%
      of the cell RNA content, respectively. Protein nutritive value was 70% of casein
      when measured by the protein efficiency ratio (PER), and over 90% of casein when
      net protein utilization (NPUa) was the criteria of evaluation.

PMID- 9530614
TI  - Effect of chronic administration of alcoholic beverages and seasoning containing
      alcohol on hepatic ethanol metabolism in mice.
AB  - Five-week-old male mice, C3H/HeNCrj (C3H/He), were given a 5% (v/v) ethanol
      solution, commercial alcoholic beverages (Japanese sake (sake) or red wine) or a
      Japanese seasoning (mirin [containing ethanol and a large amount of glucose]) ad
      libitum for 45 d, and were then examined for changes in the hepatic enzymes
      related to ethanol metabolism 2 h after oral administration of 5 g of ethanol/kg
      body weight. The specific activity of aniline hydroxylase (ANH) in the hepatic
      microsome increased significantly in all groups chronically administered ethanol
      solution, sake, red wine or mirin, and the greatest increase was in the hepatic
      microsome of mirin-administered mice. The cytochrome P-450 (CYP) 2E1 increased in
      the hepatic microsome of the mice administered ethanol solution, red wine or
      mirin where accompanied by high ANH activity. The immunoreactive band for CYP1A1
      showed high specificity in the microsome of mice given sake, red wine or mirin.
      It was assumed that CYP1A1 was induced by unknown component(s) other than ethanol
      in these solutions. In the cytosolic fraction, following the chronic
      administration of sake and mirin, the total aldehyde dehydrogenase (A1DH)
      activity with high-Km decreased significantly. In the mitochondrial fraction, the
      activity of high-Km A1DH increased significantly in the mirin-administered mice
      which drank a large amount of ethanol, whereas that in the red wine-administered
      group tended to decrease. These results indicate that the enzyme activities
      related to the oxidation of both ethanol and acetaldehyde in the cytosolic,
      mitochondrial and microsomal fractions of the liver were affected by either the
      action of ethanol or its interaction with other constituents of sake, red wine
      and mirin.

PMID- 9530615
TI  - High phosphorus diet rapidly induces nephrocalcinosis and proximal tubular injury
      in rats.
AB  - The development of nephrocalcinosis and the time course of changes in kidney
      function, especially proximal tubular function, were studied in young male rats
      fed a high-phosphorus diet. The animals were fed a purified diet with a
      phosphorus content of either 0.5% (normal phosphorus diet) or 1.5% (high
      phosphorus diet). In the group fed the high-phosphorus diet, nephrocalcinosis was
      found in 4 of 42 rats after 1 d of feeding and in all rats of this group at 3 d.
      The degree of nephrocalcinosis gradually increased with time. Upon histological
      observation by electron microscopy, vacuoles, lysosomes and swelling of
      microvilli in the proximal tubules were observed in rats fed the high-phosphorus
      diet after 1 d of feeding. Giant lysosomes with deposition of calcium and
      deposition of hydroxyapatite in mitochondria were observed in the proximal
      tubules of rats fed the high-phosphorus diet at 3 d. Albumin concentration in the
      urine of these rats was significantly increased at 3 d. The activity of N-acetyl
      beta-D-glucosaminidase in the urine was also significantly increased after 1 d of
      feeding the high-phosphorus diet, and then reached a plateau. The beta 2
      microglobulin concentration in the urine of rats fed the high-phosphorus diet was
      significantly increased at 14 d, and increased more toward 21 d. We concluded
      that nephrocalcinosis and injury to the proximal tubules are rapidly induced in
      rats fed a high-phosphorus diet.

PMID- 9530616
TI  - Effects of physical characteristics and dietary habits on bone mineral density in
      adolescent girls.
AB  - In the health management of bone, of most importance is how to spend the period
      until peak bone mass, that is appropriate self management for bone health.
      Therefore, we evaluated the effects of physical characteristics and dietary
      habits on the bone mineral density (BMD) of the second metacarpal bone (sigma
      GS/D: BMD) by the digital image processing method (DIP) in 197 healthy adolescent
      girls (Japanese students at a junior high school, aged 12-15 y), an important
      period of physical and bone growth. Concerning the physical characteristics of
      the subjects according to age group, body height in each age group was higher
      than the standard values for Japanese according to age, but body weights in the
      14-year-old and 15-year-old groups were significantly lower than the standard
      values for Japanese. Compared with the standard BMD values for Japanese according
      to age, BMD in the subjects was high in the 12-year-old, 13-year-old and 14-year
      old groups but low in the 15-year-old group (-7.3%). Concerning the nutritional
      state, energy, calcium (Ca), and iron intakes were insufficient in every age
      group. BMD relative to the standard BMD value for Japanese (standard value was
      regarded as 0%) was evaluated according to the ingestion frequency of Ca-rich
      foods. The relative BMD value (%) increased with the ingestion frequency of Ca
      rich foods. These results suggest that maintenance of an appropriate physique and
      adequate intake of nutrients such as Ca are important for bone growth during
      adolescence. Active promotion of educational guidance mainly on the effects of
      diet on bone health in adolescents in necessary.

PMID- 9530617
TI  - Correlation between intravenously supplied energy level and zinc metabolism in
      laparotomized rats.
AB  - We investigated the relationship between intravenous energy loading and zinc
      status in laparotomized rats. One of three test solutions consisting of 3% amino
      acid, the same amount of electrolytes (excluding zinc) and different
      concentrations of glucose were infused through the jugular vein for 5 d. The
      total energy was 109, 191 and 273 kcal/kg/d, respectively. Significantly positive
      correlations were observed between infusion energy and rat body weight changes (%
      of initial value) and between infusion energy and cumulative nitrogen balance.
      Regarding the zinc status, a negative correlation was found between infusion
      energy and plasma zinc concentration, and a positive correlation was observed
      between infusion energy and urinary zinc excretion. There was no significant
      relationship between infusion energy and hepatic zinc content. These results
      indicate that the zinc requirement might be increased when infusion energy is
      elevated and the nutritional status is improved. Zinc supplementation in the post
      operative period should be considered in light of not only catabolism but also
      anabolism. Anabolism may be more important than catabolism in regard to zinc
      metabolism under relatively mild stress.

PMID- 9530618
TI  - Dietary wheat bran modulates proliferating cell nuclear antigen-labeling index of
      the rat colorectum after treatment with 1,2-dimethylhydrazine.
AB  - We investigated whether dietary wheat bran (Wb) influences the proliferating cell
      nuclear antigen (PCNA)-labeling index (LI) of the colorectum of rats after the
      injection of 1,2-dimethylhydrazine (DMH). Male Wistar/ST rats were divided into
      four groups and given either a fiber-free diet or diets supplemented with Wb at
      the expense of the whole diet (5, 10 or 20 g/100 g diet). Then, they were
      subcutaneously injected with a single dose of DMH (20 mg/kg body weight) or the
      vehicle. At four weeks after the treatment, frozen sections of the colorectum
      were immunostained with anti-PCNA antibody (19F4). In the fiber-free group, DMH
      treatment significantly increased the PCNA-LI of the distal colon and rectum.
      Among the DMH treatment groups, the PCNA-LI of the distal colon in the Wb 5 g/100
      g diet group was significantly lower than that in the fiber-free group. The PCNA
      LI of the distal colon tended to increase as the amount of Wb supplemented was
      increased in the DMH-treated groups except for the fiber-free group. A similar
      trend was observed for the rectum. In conclusion, the ingestion of Wb diminished
      the increase in PCNA-LI in rat colorectum induced by DMH injection.

PMID- 9530619
TI  - Long-term consumption of whey hydrolysate formula by lactating women reduces the
      transfer of beta-lactoglobulin into human milk.
AB  - Food antigens transferred into breast milk sometimes cause an allergic reaction
      in exclusively breast-fed infants. This study will show whether the intake of a
      whey hydrolysate formula for lactating women (MOM HA) can reduce the appearance
      of food antigens in breast milk. Lactating women in the MOM group (n = 12)
      consumed MOM HA as a substitute for cow's milk and those in the COW group (n =
      13) consumed cow's milk for more than 4 months. After the ingestion of 200 mL of
      MOM HA and cow's milk by the women in the MOM and COW groups, respectively, the
      first breast milk samples were obtained and beta-lactoglobulin was measured using
      enzyme-linked immunosorbent assay. The number of subjects with detectable beta
      lactoglobulin (> 0.1 ng/mL) in the MOM group was two (17%), which was
      significantly less than that in the COW group (11 subjects, 85%, p < 0.01). The
      level of beta-lactoglobulin was also lower in the MOM group than the COW group (p
      < 0.01). Subsequently, the women in the MOM group consumed cow's milk and those
      in the COW group consumed MOM HA for one week; then a second sampling was
      performed. beta-Lactoglobulin was detected in three (25%) and 8 subjects (62%) in
      the MOM and COW groups, respectively. The level of beta-lactoglobulin was still
      lower in the MOM group (p < 0.05). The consumption of whey hydrolysate formula by
      lactating women over a considerable time reduces the transfer of beta
      lactoglobulin into their breast milk, and the low level can be maintained even
      after inadvertent ingestion of cow's milk.

PMID- 9530620
TI  - Absorption and distribution of tea catechin, (-)-epigallocatechin-3-gallate, in
      the rat.
AB  - To investigate the absorption and metabolism of an anticarcinogenic tea catechin,
      (-)-epigallocatechin-3-gallate (EGCg), in rats, a newly developed
      chemiluminescence-detection high-performance liquid chromatography (CL-HPLC)
      method was employed and the EGCg concentrations in blood plasma, liver, brain,
      small intestinal mucosa and colon mucosa were determined before and after EGCg
      administration. The recovery of EGCg, extracted consecutively with ethyl acetate
      and methanol, was 86.1% from plasma and 64.5-74.2% from the tissue samples. The
      EGCg concentrations of plasma and tissue samples from the control rat (before
      EGCg administration) were all below the detection limit (< 0.002 nmol/mL, 0.002
      nmol/g), but 60 min after a single oral administration of EGCg (500 mg/kg body
      weight), the levels increased, reaching 12.3 nmol/mL in plasma, 48.4 nmol/g in
      liver, 0.5 nmol/g in brain, 565 nmol/g in small intestinal mucosa and 68.6 nmol/g
      in colon mucosa. The EGCg levels found in the tissues corresponded to 0.0003
      0.45% of ingested EGCg. The results indicate that tea catechin, EGCg, is absorbed
      from the digestive tract, with the intestinal mucosa the most enriched of the
      organelles. This may explain the potent antioxidant function of EGCg in
      inhibiting colon mucosal phospholipid hydroperoxidation in the prevention of rat
      colonic carcinogenesis.

PMID- 9530621
TI  - Generation of mutant mice with large chromosomal deletion by use of irradiated ES
      cells--analysis of large deletion around hprt locus of ES cell.
AB  - A method of generating mice from embryonic stem (ES) cells with a large
      chromosomal deletion produced by X-ray irradiation has been developed. Fifty-two
      mutant ES clones were made that carried a nested set of chromosomal deletions up
      to approximately 10 cM in length around the hprt locus on the X Chromosome (Chr).
      Germline chimeras were generated from three ES clones with deletions ranging from
      200 to 700 kb. In germline male mice from two independent clones, deletions
      around the hprt locus yielded a runty phenotype or caused death at birth. The
      runty mice had approximately 1/3 the body weight and size of wild littermates and
      did not survive more than 3 weeks after birth. The most plausible cause of these
      phenotypes is defects in regions flanking the hprt locus. This method of creating
      mutant mice with a large chromosomal deletion is very useful for the
      identification and understanding of gene functions.

PMID- 9530623
TI  - Localization of two insulin-dependent diabetes (Idd) genes to the Idd10 region on
      mouse chromosome 3.
AB  - Multiple genes control the development of autoimmune diabetes both in humans and
      in the nonobese diabetic (NOD) strain of mouse. Previously, three insulin
      dependent diabetes (Idd) genes, Idd3, Idd10, and Idd17, were localized to mouse
      Chromosome (Chr) 3. The B10- or B6-derived resistance alleles at Idd10 and Idd3
      together provide the NOD mouse with nearly complete protection from diabetes. In
      the present study, the 10.2-cM region encoding Idd10 was defined further with
      newly developed congenic strains. A locus, located in the centromeric 2.1 cM of
      the 10.2 cM region, contributed to the Idd10 trait. However, this locus did not
      account for the full effect of Idd10, suggesting the presence of a second gene in
      the distal portion of the 10.2-cM region. This second gene is designated as Idd18
      and is localized to a 5.1-cM region. The resolution of the originally defined
      Idd3 locus into at least four separate loci, Idd3, Idd10, Idd17, and Idd18,
      illustrates the complex polygenic nature of diabetes.

PMID- 9530622
TI  - Molecular cloning of a novel mouse gene with predominant muscle and neural
      expression.
AB  - Because numerous diseases affect the muscle and nervous systems, it is important
      to identify and characterize genes that may play functional roles in these
      tissues. Sequence analysis of a 106-kb region of human Chromosome (Chr) 19q13.2
      revealed a novel gene with homology to the Neuroendocrine-specific protein (NSP),
      and it has, therefore, been designated NSP-like 1 (Nspl1). We isolated the mouse
      homolog of this gene and performed extensive expression analysis of both the
      mouse and human genes. The mouse Nspl1 gene is alternatively spliced to produce
      two major transcripts: a 2.1-kb mRNA that is expressed at highest levels in the
      brain, and a 1.2-kb transcript that is primarily expressed in muscle. The larger
      message contains 10 exons, whereas the smaller transcript contains 7 exons. The
      last 6 exons, which are present in both transcripts, share significant amino acid
      sequence identity with the endoplasmic reticulum-bound portion of NSP. Mouse and
      human Nspl1/NSPL1 genes have expression patterns that are similar to that of the
      dystrophin gene. In addition, the putative regulatory domains of Nspl1 appear
      similar in composition and distribution to the defined dystrophin regulatory
      sequences.

PMID- 9530624
TI  - Correlation between genetic and cytogenetic maps of the rat.
AB  - To correlate rat genetic linkage maps with cytogenetic maps, we localized 25 new
      cosmid-derived simple sequence length polymorphism (SSLP) markers and 14 existing
      genetic markers on cytogenetic bands of chromosomes, using fluorescence in situ
      hybridization (FISH). Next, a total of 58 anchor loci, consisting of the 39 new
      and 19 previously reported ones, were integrated into the genetic linkage maps.
      Since most of the new anchor loci were developed to be localized near the
      terminals of the genetic or cytogenetic maps for each chromosome, the orientation
      and coverage of the whole genetic linkage maps were determined or confirmed with
      respect to the cytogenetic maps. Thus, we provide here a new base for rat genetic
      maps.

PMID- 9530625
TI  - Congenic strain confirms putative quantitative trait locus for body weight in the
      rat.
AB  - Quantitative trait loci (QTLs) affecting body weight were investigated in the
      backcross population derived from non-diabetic BB/OK and spontaneously
      hypertensive rat (SHR) strains. The F1 hybrids were backcrossed onto SHR rats,
      and QTL analysis was performed separately with the resulting backcross
      populations for each sex on Chromosomes (Chrs) 1, 3, 4, 10, 13, and 18. The body
      weight was determined at the age of 14 weeks, and the statistical analysis was
      performed with MAPMAKER/QTL 1.1b computer program. According to the stringent
      threshold for a lod score of 3.0, markers on Chr 1 were found to be linked with
      body weight. The QTL with a peak lod score (5.1) on Chr 1 for a male population
      was located within markers Igf2 and D1Mgh12. In contrast, in the female
      population the body weight affecting QTL (lod = 5.7) on Chr 1 was located between
      the D1Mit3 and Lsn markers. The existence of QTLs on Chr 1 affecting body weight
      in the male population was confirmed by congenic BB.Sa rats, carrying chromosomal
      region of SHR (Sa-Igf2) on the genetic background of BB rat.

PMID- 9530626
TI  - Mapping of FASN and ACACA on two chicken microchromosomes disrupts the human 17q
      syntenic group well conserved in mammals.
AB  - Fatty acid synthase and Acetyl-CoA carboxylase are both key enzymes of
      lipogenesis and may play a crucial role in the weight variability of abdominal
      adipose tissue in the growing chicken. They are encoded by the FASN and ACACA
      genes, located on human Chromosome (Chr) 17q25 and on Chr 17q12 or 17q21
      respectively, a large region of conserved synteny among mammals. We have
      localized the homologous chicken genes FASN and ACACA coding for these enzymes,
      by single-strand conformation polymorphism analysis on different linkage groups
      of the Compton and East Lansing consensus genetic maps and by FISH on two
      different chicken microchromosomes. Although synteny is not conserved between
      these two genes, our results revealed linkage in chicken between FASN and NDPK
      (nucleoside diphosphate kinase), a homolog to the human NME1 and NME2 genes (non
      metastatic cell proteins 1 and 2), both located on human Chr 17q21.3, and also
      between FASN and H3F3B (H3 histone family 3B), located on human Chr 17q25. The
      analysis of mapping data from the literature for other chicken and mammalian
      genes indicates rearrangements have occurred in this region in the mammalian
      lineage since the mammalian and avian radiation.

PMID- 9530627
TI  - Genomic DNA sequence of Rhesus (M. mulatta) cystic fibrosis (CFTR) gene.
AB  - Cystic fibrosis is a common human genetic disease caused by mutations in CFTR, a
      gene that codes for a chloride channel that is regulated by phosphorylation and
      cytosolic nucleotides. As part of a program to discover natural animal models for
      human genetic diseases, we have determined the genomic sequence of CFTR in the
      Rhesus monkey, Macaca mulatta. The coding region of rhesus CFTR is 98.3%
      identical to human CFTR at the nucleotide level and 98.2% identical and 99.7%
      similar at the amino acid level. Partial sequences of flanking introns (5582 base
      pair positions analyzed) revealed 91.1% identity with human introns. Relative to
      rhesus intronic sequence, the human sequences had 27 insertions and 22 deletions.
      Primer sequences for amplification of rhesus genomic CFTR sequences are provided.
      The accession number is AF013753 (all 27 exons and some flanking intronic
      sequence).

PMID- 9530628
TI  - Endothelin receptor B polymorphism associated with lethal white foal syndrome in
      horses.
AB  - Overo lethal white syndrome (OLWS) is an inherited syndrome of foals born to
      American Paint Horse parents of the overo coat-pattern lineage. Affected foals
      are totally or almost totally white and die within days from complications due to
      intestinal aganglionosis. Related conditions occur in humans and rodents in which
      mutations in the endothelin receptor B (EDNRB) gene are responsible. EDNRB is
      known to be involved in the developmental regulation of neural crest cells that
      become enteric ganglia and melanocytes. In this report we identify a polymorphism
      in the equine EDNRB gene closely associated with OLWS. This Ile to Lys
      substitution at codon 118 is located within the first transmembrane domain of
      this seven-transmembrane domain G-protein-coupled receptor protein. All 22 OLWS
      affected foals examined were homozygous for the Lys118 EDNRB allele, while all
      available parents of affected foals were heterozygous. All but one of the parents
      also had an overo white body-spot phenotype. Solid-colored control horses of
      other breeds were homozygous for the Ile118 EDNRB allele. Molecular definition of
      the basis for OLWS in Paint Horses provides a genetic test for the presence of
      the Lys118 EDNRB allele and adds to our understanding of the basis for coat color
      patterns in the horse.

PMID- 9530629
TI  - Mapping of the human Ca2+ channel beta 4 subunit to 2q22-23 and its expression in
      developing mouse.

PMID- 9530630
TI  - Comparison of YACs containing mouse centromeric satellite sequences cloned in
      rad52 and RAD52 host strains.

PMID- 9530632
TI  - Chromosomal location and tissue expression of the gene encoding the adenovirus
      E1A-regulated transcription factor E4F in humans and mice.

PMID- 9530631
TI  - Cloning and chromosomal localization of mouse keratocan, a corneal keratan
      sulfate proteoglycan.

PMID- 9530633
TI  - Genetic isolation of iddm 1 on chromosome 4 in the biobreeding (BB) rat.

PMID- 9530634
TI  - Structure of the human biotinidase gene.
AB  - Biotinidase cleaves biotin from biocytin, thereby recycling the vitamin. We have
      determined the structure of the human biotinidase gene. A genomic clone,
      containing three exons that code for the mature enzyme, was obtained by screening
      a human genomic bacteriophage library with the biotinidase cDNA by plaque
      hybridization. To obtain a clone containing the most 5' exon of the biotinidase
      cDNA, a human PAC library by PCR was screened. The human biotinidase gene is
      organized into four exons and spans at least 23 kb. The 5'-flanking region of
      exon 1 contains a CCAAT element, three initiator sequences, an octamer sequence,
      three methylation consensus sites, two GC boxes, and one HNF-5 site, but has no
      TATA element. The region from nt -600 to +400 has features of a CpG island and
      resembles a housekeeping gene promoter. The structure and sequence of this gene
      are useful for identifying and characterizing mutations that cause biotinidase
      deficiency.

PMID- 9530635
TI  - Twelve genes, including the unassigned proteasome zeta subunit gene, ordered
      within the human 1p13 region.

PMID- 9530636
TI  - Structure and organization of the human carboxyl ester lipase locus.

PMID- 9530637
TI  - The mouse homologs of human GIF, DDB1, and CFL1 genes are located on chromosome
      19.

PMID- 9530638
TI  - Interleukin-1 receptor-associated kinase gene Il1rak maps to the mouse X
      chromosome.

PMID- 9530639
TI  - A cluster of stearoyl CoA desaturase genes, Scd1 and Scd2, on mouse chromosome
      19.

PMID- 9530640
TI  - [Signal transduction in photoreceptor cells].
AB  - Vertebrate photoreceptors respond to light with a brief hyperpolarization of
      their membrane potential. In the dark, photoreceptors are depolarized by cation
      influx through channels in the plasma membrane which are kept open by the second
      messenger cGMP. Light absorption activates an enzyme cascade that hydrolytically
      destroys cGMP, resulting in channel closure and hyperpolarization of the
      membrane. In addition, processes are initiated that allow photoreceptors to adapt
      their sensitivity to the ambient illumination. Although these adaptational
      mechanisms are less well understood, it is clear that they are strongly
      controlled by the intracellular Ca2+ concentration. This review describes our
      present knowledge about the signal transduction and its fine tuning by a complex
      network of Ca(2+)-mediated processes in vertebrate photoreceptors.

PMID- 9530641
TI  - [Immunologic foundations of new vaccination strategies].
AB  - Vaccines provide cost-efficient means for control of infectious diseases. Yet,
      several infectious diseases exist, for which efficacious vaccines are not
      available, as yet. Recent progress in immunology has led to the identification of
      the parameters which promote the development of the most appropriate immune
      response that develops against a given infectious agent. Major criteria are the
      conditions of intracellular antigen processing which regulate activation of CD4
      or CD8 T-cells. CD4 T-cells play a major role in the control of intracellular
      bacteria, protozoa and fungi, and CD8 T-cells are of importance for combat of
      viruses and certain intracellular microbes that evade from the phagosome into the
      cytoplasm. Equally important are the conditions which dictate the development of
      T-cell populations secreting distinct cytokine patterns of Th1 or Th2 type with
      Th1 cells being responsible for combat of intracellular bacteria and Th2 cells
      playing a major role in the control of helminth infections. Understanding how the
      host regulates the development of the most appropriate defence mechanisms
      together with modern insights into molecular genetics for manipulation of
      microbial agents will promote the development of a novel generation of vaccines.
      Such vaccines will not only contribute to control of infectious agents, but also
      allow novel strategies towards therapy of tumors, autoimmune disease and allergy.

PMID- 9530642
TI  - Influence of D(-) and L(+) tartaric acid on lysozyme adsorption onto a Si(Ti)-O2
      surface.

PMID- 9530643
TI  - Influence of arginine, omega-3 fatty acids and nucleotide-supplemented enteral
      support on systemic inflammatory response syndrome and multiple organ failure in
      patients after severe trauma.
AB  - This study investigated the influence of an enteral diet supplemented with
      arginine, omega-3 fatty acids, and nucleotides (Impact, Sandoz Nutrition, Berne,
      Switzerland) on the incidence of systemic inflammatory response syndrome (SIRS)
      and multiple organ failure (MOF) in patients after severe trauma. Thirty-two
      patients with an injury-severity score > 20 were included in this prospective,
      randomized, double-blind, controlled study. Primary endpoints were the incidence
      of SIRS and MOF. Secondary endpoints were parameters of acute phase and immune
      response as well as infection rate, mortality, and hospital stay. For statistical
      analysis 29 patients (test group n = 16, control n = 13) were eligible. In the
      test group, significantly fewer SIRS days per patient were found during 28 d. The
      difference was highly significant between d 8-14 (P < 0.001). MOF score was
      significantly lower in the test group on d 3 and d 8-11 (P < 0.05). Acute phase
      parameters showed lower C-reactive protein serum levels (significant on D day 4)
      and fibrinogen plasma levels (significant on d 12 and 14; P < 0.05). HLA-DR
      expression on monocytes showed significantly higher fluorescence activity on d 7.
      No significant difference was found for T-lymphocyte CD4/CD8 ratio, interleukin-2
      receptor expression, infection rate, mortality (2/16 vs. 4/13), and hospital
      stay. The results of the study provide further support for beneficial effects of
      arginine, omega-3-fatty acids and nucleotide-supplemented enteral diet in
      critically ill patients.

PMID- 9530644
TI  - The influence of amino acid source on the stability of ascorbic acid in TPN
      mixtures.
AB  - This study was undertaken to investigate the stability of ascorbic acid and its
      primary degradation product, dehydroascorbic acid, in total parenteral nutrition
      (TPN) mixtures. The influence of the type of bag and the commercial source of
      amino acid on ascorbate degradation was examined, using a stability-indicating
      high-pressure liquid chromatography (HPLC) method. Ascorbic acid was most stable
      in multilayered bags, compared with ethylvinyl acetate (EVA) bags. Results
      indicated that, in multilayered bags, the initial rapid ascorbic acid degradation
      was greatest in TPN mixtures containing amino acid infusions without reducing
      activity. In contrast, degradation in TPN mixtures containing amino acids with
      reducing compounds (Vamin 14 and Freamine III 8.5%) was less than 10% of the
      added amount. Dehydroascorbic acid degraded approximately in parallel with
      ascorbic acid, and it contributed to the total available ascorbate activity. The
      addition of air to TPN mixtures in multilayered bags caused accelerated
      degradation of both ascorbic acid and dehydroascorbic acid. It is concluded that
      TPN mixtures compounded in multilayered bags can be safely assigned extended
      shelf lives, especially if compounded using an amino acid with reducing activity.
      This is principally due to the protective effect of the bag wall in preventing
      oxygen transmission, the cause of ascorbic acid oxidation, because oxygen
      transmission through the bag wall is minimized during storage. TPN mixtures
      stored in EVA bags should be administered within 2-4 d of compounding, depending
      on the amino acid infusion used.

PMID- 9530645
TI  - Lipid peroxidation of i.v. lipid emulsions in TPN bags: the influence of
      tocopherols.
AB  - Four commercial i.v. lipid emulsions containing soybean oil were investigated to
      determine the tocopherol content. A sensitive high-performance liquid
      chromatography (HPLC) on a diol column was established to quantitate the
      tocopherol isomers in lipid emulsions. A previously described iodometric
      titration was used to assess the peroxide value (mmol peroxides/L). The pH was
      measured also. The initial tocopherol concentration ranges in three of the four
      commercial soybean oil-based 20% lipid emulsions studied were compared ([mg/L]:
      alpha: 17-23, beta: 4, gamma: 88-129, delta: 40-44). One product showed an
      increased alpha-tocopherol content (172 mg/L) due to supplementation during
      manufacture. During storage in an ethylvinyl acetate (EVA) bag at 40 degrees C
      under light-protection (LP) for 34 d, a lipid emulsion 20% with a natural alpha
      tocopherol content showed a peroxide value (PV) of 9.18 (about 450 times the
      value of controls in glass bottles) with a concomittant reduction of the
      tocopherol isomers to 61.6% (alpha), 86.5% (gamma), and 88.9% (delta) compared to
      the initial values. Comparison of two lipid emulsions with different amounts of
      alpha-tocopherol (Lipidem 20%, B. Braun, Switzerland: 156.29 mg/L vs. Intralipid
      20%, Pharmacia Upjohn, Switzerland: 8.75 mg/L) for their antioxidative capacity
      using the same stress conditions revealed for the emulsion with the high alpha
      tocopherol content a significantly higher PV over the whole test period (after 5
      wk: 33.63 vs. 6.23; P < 0.001) and an increased alpha-tocopherol decomposition
      (51.6% vs. 8.7%). The drop in pH was higher, also (1.9 vs. 1.0 pH units). In
      contrast to ordinary concentrations of about 20 mg/L, alpha-tocopherol in 20%
      lipid emulsions showing antioxidative properties, a supplementation with about
      160 mg/L showed a prooxidative effect when exposed to ambient atmosphere in an
      EVA bag.

PMID- 9530646
TI  - Dilution is effective in reducing infusion phlebitis in peripheral parenteral
      nutrition: an experimental study in rabbits.
AB  - To clarify conflicting clinical results that had been reported as to whether
      dilution is effective or not in reducing infusion phlebitis, this study was
      undertaken. We undertook two experiments with the different infusion conditions
      in rabbits to confirm the generality and the reproducibility of the results. To
      test the effect of dilution, 120 mL/kg of solution A (784 mOsm/kg) was infused
      into rabbit ear veins at 10 mL.kg-1.h-1 for 12 h, and 144 mL/kg of 1.2-fold
      diluted solution A (648 mOsm/kg) was infused at 12 mL.kg-1.h-1 for 12 h.
      Similarly, 120 mL/kg of solution B (718 mOsm/kg) was infused at 5 mL.kg-1.h-1 for
      24 h, and 168 mL/kg of 1.4-fold-diluted solution B (514 mOsm/kg) was infused at 7
      mL.kg-1.h-1 for 24 h. The infused veins were sampled 24 h after the end of the
      infusion and examined histopathologically. After the 12-h infusion, phlebitic
      changes were observed in six of eight rabbits given solution A but in only one of
      eight rabbits given diluted solution A, although the same quantities of the same
      nutrients were infused. Also, after the 24-h infusion, phlebitic changes were
      observed in six of eight rabbits given solution B but in no animals given diluted
      solution B. The same result that dilution reduced or eliminated phlebitic changes
      was confirmed in the different conditions. These results suggest that osmolality
      of the infusion solution is an important factor in the development of phlebitis
      regardless of infusion volume or infusion rate and that dilution is effective in
      reducing the phlebitic potential of infusion solutions.

PMID- 9530647
TI  - The effect of meal size on postprandial carbohydrate metabolism in normal and
      tumor-bearing rats.
AB  - Doubling the size of a meal causes less than a two-fold increase in the thermic
      effect of feeding. One possible reason for this is that larger meals may be
      associated with a change in the pathway of postprandial hepatic glycogen
      synthesis from the indirect pathway, involving gluconeogenesis, to the more
      energetically efficient direct pathway. We have therefore investigated the effect
      of meal size on the relative contributions of those two pathways both in normal
      rats and in tumor-bearing rats, which have previously been shown to utilize the
      indirect pathway to a greater extent. Rats bearing a transplantable Leydig cell
      tumor and freely fed controls were fasted overnight and given a test meal
      amounting to 12 or 24 kJ of their normal diet. They were then injected with 3H2O
      and 14C-glycerol and killed one hour later. The total amount of 3H incorporated
      into liver glycogen was not affected by meal size, although it was greater in
      tumor-bearing rats than controls. Analysis of the 3H labelling at different
      positions in the glycogen glucose residues showed that the proportion of glycogen
      synthesized via pyruvate, which tended to be greater in tumor-bearing rats, was
      significantly reduced by increasing the size of the meal. Glycogen synthesis from
      glycerol was not affected by either meal size or tumor growth. Increasing the
      size of the meal increased the rate of fatty acid synthesis in both the liver and
      the epididymal fat pad, but not the tumor. Thus increasing the size of the meal
      appeared to increase the proportion of glycogen synthesized by the direct pathway
      from glucose in both tumor-bearing and control animals.

PMID- 9530648
TI  - Cancer prevention studies: past, present, and future directions.
AB  - In spite of extensive research on vitamins and diet, a consistent beneficial role
      of vitamin supplements, together with diet modification in human cancer
      prevention, has not been demonstrated. Published results of human intervention
      trials with vitamin supplements have been contradictory. This review critically,
      but briefly, evaluates (a) current concepts of human carcinogenesis, (b) effects
      of vitamins on biochemical parameters that are pertinent to cancer prevention,
      and (c) whether past or current protocols for intervention trials among high-risk
      populations adopt specific scientific rationales that are based on laboratory and
      human epidemiology studies. In addition, we propose a novel experimental design
      for intervention trials among high-risk human populations that is based on sound
      scientific principles derived from laboratory and human epidemiologic data on
      vitamins, diet, lifestyle, and cancer prevention. Such trials would answer a
      fundamental public health issue of today: Does supplementation with multiple
      vitamins, together with diet and lifestyle modifications, reduce the risk of
      cancer?

PMID- 9530649
TI  - Is the risk of urinary tract tumorigenesis enhanced by a marginal chronic
      essential fatty acid deficiency (EFAD)?
AB  - A considerable amount of experimental, clinical and epidemiological data indicate
      that dietary fats play a role in urinary tract tumorigenesis. In rodents, chronic
      essential fatty acid (EFA) deficiency seems to induce both urolithiasis and
      transitional hyperplasias, followed by a tendency for tumorigenesis of the
      urinary passages. High intake of saturated fats or non-EFAs, conditions that may
      induce EFA deficiency (EFAD) increase the risk of bladder cancer in case-control
      studies. In other cell populations, EFAs are beneficial as preventive and
      therapeutic nutrients for the treatment of cancer. Thus, it is reasonable to
      assume that abnormal metabolism and/or nutritional deprivation of EFA, by
      inducing a chronic or a subclinical EFA deficiency, may enhance the risk of
      urothelial tumorigenesis.

PMID- 9530650
TI  - Nutrition and infection in tropical countries--implications for public health
      intervention--a personal perspective.
AB  - Although the health and nutritional status of populations in many countries in
      the tropical and subtropical zones in Africa, Latin America, and Asia have
      improved considerably, nutritional problems and the burden of infectious diseases
      are still a major public health concern. This review presents the
      interrelationship between infections and the nutritional status of preschool
      children with an emphasis on "protein-energy-deficiency" on a community basis.
      Common nutritional indicators of subclinical undernutrition are the proportion of
      underweight, wasting, and stunting in children. These anthropometric nutritional
      indicators are also proxy indicators of the overall well-being of the child
      population. They reflect, in particular, the burden of infectious diseases on the
      community. Also in subclinical undernutrition, infectious diseases and often ill
      defined spells of illness negatively affect nutritional status. A reduced
      nutritional status increases the risk of infections. Infectious diseases and
      undernutrition interact synergistically. In most countries, available resources
      are adequate to improve the nutritional status of the population and reduce
      illness spells; that is, if the population could be motivated to take health
      related actions and have the active support of the health delivery sector on a
      community level.

PMID- 9530651
TI  - Influences on diet, health behaviours and their outcome in select ethnocultural
      and religious groups.
AB  - Diverse cultural components of behavior may have significant impacts on patterns
      of eating, drinking, and social interaction, irrespective of socioeconomic
      status. For example, the major world religions prescribe or proscribe specific
      dietary behaviors; some of these are rooted in historical or geographical origins
      as well as group folklore; and they have integral roles as expressions of
      religious piety and group cohesiveness. The literature is replete with ecological
      observations of between-country differences in disease trends, some of which have
      been associated with dietary practices. The study of distinct cultural and
      religious groups (especially migrants acculturating to new environments) and the
      extent to which they adhere to culturally-based dietary precepts, has advanced
      our knowledge of psychosocial influences on food habits, nutritional adequacy,
      and overall health. However, a relatively small proportion of culturally-based
      research studies conducted to date have explored cross-cultural, ethnic, or
      religious variables. This paper reviews some population-based differences in
      dietary habits and other behaviors by ethnocultural group or religious
      denomination; health consequences and suggestions for future research are
      discussed.

PMID- 9530652
TI  - Vitamin C deficiency in Asian women.

PMID- 9530653
TI  - Infusion phlebitis and peripheral parenteral nutrition.

PMID- 9530654
TI  - Fatty acids and cancer.

PMID- 9530655
TI  - Culture, religion, diet and health: challenges and opportunities.

PMID- 9530656
TI  - Dietary fish oil supplementation in IgA nephropathy: a therapy in search of a
      mechanism?

PMID- 9530657
TI  - Preventing diabetes complications: living up to the promise.

PMID- 9530658
TI  - Latest developments in the treatment of severe malnutrition in children.

PMID- 9530659
TI  - Antioxidant supplements and colorectal cancer.

PMID- 9530660
TI  - Economic issues in nutrition research.

PMID- 9530661
TI  - Detection of particulate material in parenteral nutrition admixtures.

PMID- 9530662
TI  - Whither health care inflation.

PMID- 9530663
TI  - [Bone substitution materials. Current status and prospects].
AB  - For the treatment of bony defects of the human skeleton there are different
      options. If a defect has to be filled up, autogenous cancellous bone is
      recommended as the 'golden standard', i.e. the material of choice for such
      procedures, ignorant to the fact that autogenous bone transplants are not without
      consequences to the patient and that their harvesting and transplantation might
      be connected to certain complications. As an alternative, there have been
      attempts to implant bone replacement materials as a substitute for the autogenous
      tissue. Despite a longstanding history of research in this field up to now a
      clinically applicable alternative could not have been found. Aim of the article
      is to classify the different compounds recommended for bone replacement. After a
      description of the development of the materials in the different classes, the
      state of the art and today's knowledge of how the different materials elicite
      their effects, an outlook into possible future developments is given for each
      class. Finally recommendations for today's clinical use of the bone substitutes
      are presented.

PMID- 9530664
TI  - [Defect reconstruction using demineralized bone matrix. Experimental studies on
      piglets].
AB  - The aim of this study was to evaluate the bone stimulation forced by
      Demineralized Bone Matrix (DBM)-Chips and-Gel in comparison to the bone-ingrowth
      into a porous hydroxylapatite ceramic (Endobon) in mini pigs. The following
      results were obtained: 1. DBM-Chips and DBM-Gel did not stimulate bone healing
      when filled into cancellous bone defects. The defect did not heal within 12
      weeks. 2. Up to 35 days the least amount of new bone formation was observed
      within porous hydroxylapatite ceramic. Up to 12 weeks complete bone ingrowth in
      to the ceramic has been seen with close bonding between new formed bone and the
      ceramic trabeculae. 3. By continuous labelling with fluorochromes the new bone
      formation could be analysed by fluorescence microscopy and the dynamics could be
      related to time after implantation.

PMID- 9530665
TI  - [Biologic reactions to calcium phosphate ceramic implantations. Results of animal
      experiments].
AB  - Calciumphosphate-ceramics have been intensively investigated as bone replacement
      materials for more than twenty years. In consequence to numerous experimental as
      well as clinical implantations Tricalciumphosphate-ceramic and Hydroxyapatite
      ceramic proved to be the most suitable substances. Nevertheless, due to several
      shortcomings, these synthetic bone replacement materials can up to now in no way
      replace autogenous bone, the 'golden standard', for all indications of the
      clinical setting. The reason for this is that despite our ever increasing
      knowledge of materials' and host bed properties we still are unable to securely
      predict the outcome after the implantation of such synthetic substitutes. The
      article reviews the most important biological reactions in mammals and explains
      the underlying causes.

PMID- 9530666
TI  - [Effect of hydroxyapatite layering on the osteo-integration of weightbearing and
      non-weightbearing implants. Comparison to other microporous surfaces in animal
      experiments].
AB  - In case of non cemented fixation of prosthesis an extensive osseointegration is a
      precondition to obtain long lasting biological anchorage of the implant. The aim
      of the presented study was to analyse, whether the use of biactive materials (in
      case of prostheses-hydroxylapatit-coating-) provides advantages concerning the
      quality of anchorage compared to biotolerant or bionert materials. The influence
      of grade of biocompatibility of materials, the surface structure, the period of
      investigation and weightbearing on the osseointegration of implants was evaluated
      in an animal experimental study. New Zealand White rabbits got implanted
      cylinders in the non weightbearing series and spacers in the weightbearing series
      in the distal femur. The implant materials were spongy metal, porous coated
      titanium and hydroxylapatit coated titanium. After the experimental period of 4,
      8 respectively 12 weeks the implant bearing femur underwent histological,
      morphometrical and scanning electromicroscopical investigation. The amount of
      osseointegration was determined by using the automatical image analysis. The
      percentage of new build bone was investigated by fluorescence microscopy and the
      adhesive power by push out tests. For non weightbearing implants higher adhesive
      powers were measured compared to hydroxylapatit coated implants while
      osseointegration was identic. All primary press-fit anchored weightbearing
      implants showed osseointegration. In hydroxylapatit coated specimen the most
      intensive osseointegration was found however without influence on the adhesive
      power. This fact was caused by the delamination of the plasma coating as
      consequence of the insufficient attachment of the hydroxylapatit coat to the
      metal nucleus.

PMID- 9530667
TI  - [Integration properties of bone substitute materials. Experimental studies on
      animals].
AB  - In order to avoid the potential risks of disease transmission in allograft
      surgery, numerous substitute materials have been described. As the biological
      response to implant materials is different, we undertook the following study to
      assess type and amount of bone ingrowth in CaP-ceramics. 105 cylindrical bone
      defects with a diameter of 5.4 mm were created surgically in the femoral condyles
      of 53 skeletal mature NZW rabbits. The defects were filled with crushed coralline
      hydroxyapatite (HA) implants (n = 21), synthetically produced hydroxyapatite (n =
      21) and surface-modified alpha-Tricalciumphosphate (TCP) grains (n = 21). 21
      defects were left empty and other drill holes were filled with rabbit cancellous
      bone cylinders (n = 21) after 3 months of cryopreservation at -78 degrees C
      without sterilization. Following observation periods of 2, 4, 6, 8, 12, 26 and 52
      weeks the femoral condyles were harvested for histological evaluation and
      quantitative analysis of bone ingrowth. Woven bone formation at implant periphery
      can be observed in all substances as early as 2 weeks postoperatively. At 4-week
      intervals cryopreserved allografts show new bone apposition on surfaces of
      necrotic trabeculae and graft-host junctions by a predominantly osteoblastic
      reaction at the periphery of all cylinders, while in HA- and TCP-grains early
      bone formation in the center of drill holes is detectable as well. There is a
      direct contact between HA-/TCP-particles and newly formed bone without fibrous
      tissue formation at the implant surfaces. Central new bone formation in rabbit
      allografts can be observed after 6 to 8 weeks together with a secondary
      osteoclastic resorption of necrotic transplant trabeculae. The result of this
      remodeling process is a complete degradation of transplant cylinders with
      reorganization of vital trabeculae oriented in a mature pattern after 12 to 26
      weeks. In contrast the HA- and TCP-implants did not show any signs of resorption.

PMID- 9530668
TI  - [Bone regeneration stimulated by bone substitute materials].
AB  - Prompted by severe problems in autogeneic and allogeneic bone transplantation,
      intensive efforts were made to find sufficient substitutes. A main demand on
      these materials, especially in healing of osseous defects, is to achieve results
      comparable to those of auto- or allografts. These must be related to their
      biomechanical and particularly to their biological properties, i.e. the ability
      to form new bone, osseous integration and physiological remodeling. Within
      different trials in the tibiae of sheep we investigated bone substitutes like
      hydroxyapatite ceramics (HA) or partially demineralized bone matrix (pDBM) and
      compared them to the gold standards of autogeneic and allogeneic bone
      transplantation. Therefore we used two different models: the drill hole model
      with small size defects of 6 mm in diameter and the shaft defect model as a true
      to-life defect with a 5 cm large diaphyseal defect. Evaluation was done by X
      rays, histology, microradiography, fluorescent microscopy and morphometry of the
      small size defects. HA showed only small effects on new bone formation and works
      merely as an osteoconductor. However, excellent new bone formation was regularly
      achieved by pDBM in the small defects, whereas it was limited in the large size
      defects. But considering their mechanism of action, it is possible to bridge
      large bone defects by pDBM.

PMID- 9530669
TI  - [Pyrost, a spongious, mineral bone substitute. Experimental bases and 13-year
      clinical experience in over 1000 cases].
AB  - In different animal investigations Pyrost demonstrated osteoconductive and
      osteostimulative effects. In ectopic tissues and especially in conditions of low
      osteogenetic potency, the combination of Pyrost and autogenic bone marrow effects
      bone formation. In a clinical prospective study, Pyrost was implanted in 1117
      cases in the following indications: Donor site defects after bone
      transplantation, bone defects after tumor resection, revision of THA,
      acetabuloplasty, fracture treatment, pseudarthrosis and lengthening osteotomy,
      spondylodesis. In 87.3% the regeneration of the bone defects was complete, in 8%
      a partial regeneration was found. Excessive bone formation took place in 2.7%,
      insufficient regeneration in 2.0% in cases of instability or infection. According
      to the clinical results Pyrost is a suitable bone substitute in small bone
      defects and it is a valuable completion to the autogenic bone graft in large
      defects. In disadvantageous bone bed Pyrost has to be augmented with bone marrow
      and in large segmental defects the combination with autogenic bone grafts is
      recommendable. Presupposition for the application of bone substitutes like Pyrost
      in large defects is a sufficient primary stability of the bone bed. The
      application in infected tissue is not favorable.

PMID- 9530670
TI  - [Type I collagen in xenogenic bone material regulates attachment and spreading of
      osteoblasts over the beta1 integrin subunit].
AB  - Xenogenic bone biomaterials have been proposed as an alternative to autografts or
      allografts in human bone restoring or in complement of prosthetic surgery. When
      appropriate treatments were applied, immunological, inflammatory, bacteriological
      or virological adverse responses can be prevented. However, these treatments may
      interact with type I collagen, the major component of the organic bone matrix.
      Type I collagen can bind osteoblasts via specific cell surface receptors, the
      integrins. In this work, two different xenogenic biomaterials were studied. Both
      biomaterials have a bovine bone origin. They displayed similar architectural
      organization with connected plates and rods and similar surface topography and
      roughness. They differed by the presence or not of collagen type I. The first one
      was characterized by preservation of the type I collagen matrix associated with
      spindle-shaped hydroxypatite crystals and the second was solely composed by heat
      modified apatite crystals. Osteoblast-like cells (Saos-2) were cultured on both
      biomaterials and examined in scanning and transmission electron microscopy after
      7 and 14 days. Both biomaterials were cytocompatible as demonstrated by good
      ultrastructural cell preservation. (1) At the surface of the collagen containing
      biomaterial, cells were elongated in shape and oriented according to the
      trabecular architecture and to the superficial collagen network. After 14 days of
      culture, cells were confluent and the biomaterial surface was hidden by the cell
      sheet. The beta 1 integrin subunit was detected by immunogold in transmission
      electron microscopy in close relationship with the superficial collagen fibres of
      the biomaterial and with the outer cell surface. When cultures were carried out
      in presence of anti beta 1 integrin subunit, cells were packed and piled up with
      lack of specific orientation. (2) At the surface of the deproteinized
      biomaterial, cells were globular without specific disposition and often partially
      attached to the surface. After 14 days of culture, large areas of the biomaterial
      surface remained uncovered. Anti beta 1 subunits conjugated with gold particles
      were detected around the cells but with no specific association with the
      deproteinized biomaterial. These results strongly suggest that presence of type I
      collagen fibres in the matrix of a bone biomaterial is of major interest to
      determine cell attachment, spreading and orientation via interaction between type
      I collagen and beta 1 integrin subunit of osteoblasts.

PMID- 9530671
TI  - [Autogenous bone cell transplantation].
AB  - In this study the outcome of autologous bone cell transplantation in artificial
      femur defects was tested within an animal study in sheep. The bone cells were
      harvested by a small ilium biopsy and cultivated in an individual medium with 10%
      autogenous serum and 90% X-Vivo 10. After two weeks 4 millions of the cultured
      bone cells were transplanted in artificial femur defects with bone gelatin as
      carrier. The remaining cells were characterized by various tests (Alkaline
      phosphatase, osteocalcin, collagen type I, calcification). This procedure was
      tested in 24 adult male sheep. The side of transplantation was randomized by
      plan. The corresponding femur side represents the control side. After 10 days, 4,
      8 and 12 weeks animals were killed and the femura were taken for the following
      evaluation: histology, radiology, bone density and mechanical testing. The
      results show that the autologous bone transplantation leads to a significant
      higher bone regeneration in the bone defects. After ten days there was a lower
      migration of inflammation cells. After 4 weeks we find a significant increase of
      new bone formation on the transplanted side in the histological examination.
      After 8 weeks this significant difference was found even in the bone density.
      This difference increased in the 12 weeks group further on. The autogenous bone
      cell transplantation in the described way seems to be an potent method in the
      treatment of bone defects.

PMID- 9530672
TI  - [Surgical management of idiopathic scoliosis].

PMID- 9530673
TI  - Evolution to current otolaryngic allergy techniques.
AB  - The evolution of current otolaryngic allergy techniques for the diagnosis and
      management of inhalant and food allergens is presented in this article. Skin
      titration, in vivo diagnostic techniques, and symptom-relieving immunotherapy are
      emphasized for the former sensitivities and oral challenge tests, skin titration,
      and elimination or rotary diets for the latter.

PMID- 9530675
TI  - In vitro testing for allergy diagnosis. Comparison of methods in common use.
AB  - In vitro assays for the measurement of specific IgE have been available for the
      last 30 years. Over this time there have been significant changes in their
      technology, ranging from a long 3-day test to a short 3-hour test and from a
      labor intensive test to a fully automated test. These new innovations have
      enabled today's in vitro assays to be far more efficient, reliable, and
      reproducible.

PMID- 9530674
TI  - Selecting allergenic extracts for inhalant allergy testing and immunotherapy.
AB  - The proper selection of allergen extracts is important in maintaining an
      efficient allergy practice. This article discusses pollen extract selection. The
      selection of tree, grass, and weed pollen extracts depends very much on where the
      clinician's practice is located. The floral zones of the continental United
      States are discussed, and several specific lists of pollen extracts are provided.
      Mold spore, dust, dust mite, and cat allergen selection are much less geography
      specific, yet they have their own complexity.

PMID- 9530676
TI  - Allergy skin tests for inhalants and foods. Comparison of methods in common use.
AB  - Many types of skin tests have evolved from Blackley's early scratch tests. This
      review highlights both the similarities between current skin tests and their
      differences. All current skin tests are capable of detecting allergic
      hypersensitivity, but the tests differ in their sensitivity, specificity, safety,
      reproducibility, and applications. Common factors in initial and final test
      doses, and in test dose increments, are identified. Test methods that
      quantitatively measure a range of allergen concentrations have diagnostic
      advantages in terms of safely detecting a wide range of allergic sensitivities.
      Failure to detect the full spectrum of allergic disease can lead to treatment
      failure; therefore, complete skin testing is desirable. This is especially
      important when dealing with exquisitely sensitive patients, such as many grass or
      ragweed sensitized patients, but is equally vital when evaluating low sensitivity
      patients, including many who are mold or food sensitive. Quantitation also
      improves test reproducibility, which is why it is used for antigen
      standardization. Finally, quantitation has advantages when used to initiate and
      escalate allergen immunotherapy. In vivo testing continues to evolve. New types
      of prick testing devices, and refinements of intradermal and patch test methods,
      continue to be reported. All allergists need to stay current with developments in
      vivo testing, so that they can offer their patients diagnosis that is appropriate
      to each individual situation.

PMID- 9530677
TI  - Putting chemical and environmental sensitivities in perspective.
AB  - Chemical sensitivity has been recognized for an extended period. Over the last 30
      years or more, there has been a growing number of chemicals to which humans are
      being exposed. Some people have become sensitive to one or more of these
      chemicals and present this sensitivity in a wide variety of signs or symptoms.
      Single or multiple organ systems may become involved. This article is intended to
      give an overview on the existence and recognition of chemical sensitivities and
      how they may be diagnosed and treated. The important item is to educate
      physicians to the existence of chemical sensitivity and to consider this in their
      differential diagnosis when the patient presents with the signs, symptoms, or
      clinical pattern that is explained.

PMID- 9530678
TI  - Overview of otolaryngic allergy management. An eclectic and cost-effective
      approach.
AB  - Ear, nose, and throat allergic assessment plays an integral role in the
      evaluation and care of approximately 25% of patients seen in a general
      otolaryngology practice. With the advances in health care delivery and the
      influence of managed care organizations, physicians are asked to render cost
      effective evaluation and management of their patients. This article examines the
      economic issues and historical data regarding the work-up of patients with
      suspected allergic problems. Relative cost-benefits of different modalities of
      treatments, including avoidance techniques, pharmacotherapy, and immunotherapy,
      are discussed.

PMID- 9530679
TI  - Practical environmental modifications for the inhalant allergy patient.
AB  - Environmental management of inhalant allergens is an important part of a
      comprehensive allergy management program and is the most controllable aspect by
      the patient. The safest and most effective way to eliminate an allergic reaction
      is to eliminate exposure to the antigen that provokes the response. The basic
      control principles for all inhalant allergens are to (1) remove the source of the
      allergen if possible, (2) remove accumulated allergen, and (3) prevent the return
      of the allergen. This article examines the published evidence for environmental
      control measures in terms of effectiveness, cost, and ease of implementation.

PMID- 9530680
TI  - Cost-effective pharmacotherapy for allergic rhinitis.
AB  - This article provides guidelines for pharmacotherapy to maximize symptom relief
      from allergic rhinitis. Consideration of frequency, severity, and site of
      symptoms is important in directing pharmacotherapy efficacy and maximizing cost
      effectiveness. The agents available include antihistamines, decongestants,
      steroids, mast cell stabilizers, anticholinergic agents, and mucolytics.
      Appropriate indications for each and combinations of various agents are discussed
      within the context of drug efficacy, side effects, affordability, and ease of
      compliance. The direct and indirect costs of allergic rhinitis are not well
      delineated but are explored to put the costs of therapy in perspective.

PMID- 9530681
TI  - Allergy immunotherapy.
AB  - Specific immunotherapy for allergy has been used for over eight decades. Despite
      this history, controversy continues over techniques, indications, and the
      eventual outcomes. This article reviews immunotherapy techniques available to the
      various practitioners of allergy care. Safety recommendations, indications for
      therapy, and available measurements for outcomes are also discussed.

PMID- 9530682
TI  - Allergic rhinitis. Outcomes of immunotherapy on symptom control.
AB  - Recent scientific studies have demonstrated the efficacy of various forms of
      immunotherapy for the treatment of allergic diseases. Traditional subcutaneous
      immunotherapy, sublingual, oral, and intranasal immunotherapy have been shown to
      significantly reduce symptoms and favorably modulate the immune response. Outcome
      studies that use patient response data from standardized surveys represent the
      next challenge to all practicing allergists.

PMID- 9530683
TI  - Alternatives in the diagnosis and treatment of food allergies.
AB  - The diagnosis of food allergy remains a difficult and often inexact proposition,
      with the treatment being equally cumbersome and complex. For this reason a
      variety of approaches have been developed, varying in acceptance and approval.
      Although many approaches represent alternative medicine, today's alternative may
      be tomorrow's standard.

PMID- 9530684
TI  - Allergy for the otologist. External canal to inner ear.
AB  - Allergy may affect the outer, the middle, or the inner ear. Although the otologic
      manifestations of allergy are not by themselves diagnostic, the history,
      including family history and associated symptoms in other target organs, will
      often help lead to the correct diagnosis and institution of therapy. Patients
      with significant and chronic symptoms, including those with labyrinthine symptoms
      of allergy, will respond well to specific immunotherapy and/or dietary
      elimination.

PMID- 9530685
TI  - Allergy for rhinologists.
AB  - Our knowledge of the pathophysiology of allergy continues to grow, and with that
      understanding better treatment methods are being developed. An understanding of
      the appropriate diagnosis and treatment of allergy is mandatory for the physician
      who is treating patients with nasal and sinus disorders. Provision for this
      aspect of patient care will materially benefit such patients, although ignoring
      it places the physician at risk for repeated treatment failures.

PMID- 9530686
TI  - Allergy for the laryngologist.
AB  - Allergic disease can affect any portion of the respiratory tract, including the
      larynx, trachea, bronchial tree, nasal cavity, paranasal sinuses, nasopharynx,
      and pharynx. This review evaluates laryngeal manifestations of allergic disease
      and the impact of allergic mechanisms in disorders, within the scope of
      laryngology.

PMID- 9530687
TI  - Approaches to otolaryngic allergy emergencies.
AB  - The otolaryngic allergist should take every measure possible to prevent reactions
      during testing and treatment of the allergic patient. Because the risk of this
      rare complication cannot be completely eliminated, however, it is essential to be
      prepared for prompt recognition and proper treatment of an anaphylactic
      emergency. An emergency set, including airway management tools, oxygen,
      intravenous materials, and proper medication, is essential. The entire office
      staff should be educated to cope with the emergency. Finally, a medication
      history must be repeated at intervals to detect patients who are receiving beta
      blockers to either remove them from the patients' treatment regimen or to prepare
      for the special treatment of the patients on beta blockers.

PMID- 9530689
TI  - Report and proceedings of the FAO expert consultation on ticks and tick-borne
      diseases of sheep and goats. Rome, 29-30 September 1994.

PMID- 9530688
TI  - Managed care, capitation, and otolaryngic allergy.
AB  - The method of health care financing and delivery has evolved over the last decade
      with managed care making a clinical and financial impact on otolaryngology
      practices. The trend is for third-party payers to shift the financial risk of
      delivering care to the physicians. Otolaryngologists must now be versed in
      reading and negotiating managed care contracts and be cognizant of the business
      processes in their practice. Otolaryngology practices of the 90s will have to
      demonstrate competence in their ability to standardize administrative processes
      and contain administrative costs.

PMID- 9530690
TI  - Tick virus diseases of sheep and goats.
AB  - Tick-borne viruses affecting sheep and goats can be be locally important
      diseases. Viruses of the tick-borne encephalitis complex occur across Europe to
      North-East Asia and are the cause of significant losses in small ruminant
      production. Thogoto virus which can be transmitted by Ixodid ticks has been
      associated with abortion storms in sheep, it may contribute to the large
      proportion of abortions which are due to unknown causes. Nairobi sheep disease is
      the most pathogenic virus disease known for sheep and goats in East Africa.
      Ganjam virus in India may ultimately be shown to be a significant cause of
      disease in small ruminants. Some unidentified Orbiviruses have been found both in
      ticks and sick sheep, and are thought to be a cause of some losses in African
      sheep and goats. Small ruminant populations in both Africa and Asia are
      vertebrate host for Congo-Crimean haemorrhagic fever, an important human
      pathogen, and for many Arboviruses some of which are of zoonotic importance.

PMID- 9530691
TI  - Nairobi sheep disease.
AB  - Nairobi sheep disease is probably the most pathogenic virus known for sheep and
      goats. It is transmitted by an Ixodid tick, both trans-stadially and
      transovarially and causes an acute gastroenteritis. In totally susceptible
      populations, mortality rates of over 90% regularly occur. The infection also
      causes abortion. The disease is known to occur in East Africa, Somalia and
      Rwanda. It may exist in the south east of Ethiopia. No evidence for its existence
      has been found in those parts of Africa where the principle vector tick,
      Rhipicephalus appendiculatus has a seasonal breeding cycle. Thus countries like
      Zambia, Zimbabwe and Botswana appear to be free from the disease.

PMID- 9530692
TI  - Tick-borne diseases of sheep and goats caused by Babesia, Theileria or Anaplasma
      spp.
AB  - A review is given on the Babesia, Theileria, and Anaplasma species infecting
      sheep and goats. B. ovis is the most important disease agent. It is transmitted
      by Rhipicephalus bursa, R. turanicus, Hyalomma anatolicum excavatum, and probably
      by R. evertsi evertsi B. ovis is widely spread in southern Europe, the Middle
      East, and central Asia. Its geographical distribution in South and East Asia and
      in Africa is widely unknown. B. motasi obviously represents several nosodemes in
      separate regions. It is not pathogenic for intact sheep in northern Europe,
      whereas it is probably more pathogenic than B. ovis in India and northern Africa.
      The known vectors of B. motasi are Haemaphysalis punctata and R. bursa. Theileria
      hirci is transmitted by H. a. anatolicum but occurs outside the distribution area
      of this tick. Malignant theileriosis of sheep and goats is an important disease
      in Iraq, Iran, and India. An attenuated macroschizont vaccine is successfully
      being used in Iran. Anaplasma ovis is transmitted by R. bursa and probably other
      ticks in the Old World and by Dermacentor andersoni in the New World. A. ovis is
      widely spread in the Old World. Outbreaks occur only under extreme conditions.
      The identity of the tick-borne disease agents of sheep and goats and of their
      vector ticks is uncertain in many regions of the Old and the New World.

PMID- 9530693
TI  - Ticks and tick-borne diseases as a constraint to sheep and goat production in
      Italy. Selected features.
AB  - The paper reviews basic information on small ruminant production in Italy and on
      the tick species commonly found on them. A total of 13 Ixodidae species have been
      reported to parasitise sheep in the country. The tick species were belonging to
      five genera: Ixodes (two species), Haemaphysalis (four species), Dermacentor (one
      species), Rhipicephalus (three species) and Hyalomma (three species). The same
      species, with the exception of Haemaphysalis inermis and Hyalomma detritum have
      been reported also on goats. Scarse data are available on the impact of tick
      borne diseases on small ruminants productivity. The zoonotic role which may be
      played by ticks in transmitting occupationally acquired diseases to people
      involved in animal husbandry and to common public which may accidentally invade
      grazing areas is also discussed.

PMID- 9530694
TI  - Tick-borne diseases of sheep and goats and their related vectors in Iran.
AB  - Haemoparasitic diseases have long been considered as a major problem to efficient
      sheep and goats production in Iran. Theileriosis due to Theileria hirci and
      babesiosis due to Babesia ovis and B. motasi are the most pathogenic protozoa. B.
      crassa, Anaplasma ovis and Eperythrozoon ovis are usually non-pathogenic and do
      not cause any apparent problem. The major tick genera found on sheep and goats
      are Hyalomma, Rhipicephalus, Haemaphysalis, Ixodes and rarely Dermacentor
      distributed in all part of Iran. Our studies indicate that only Hyalomma ticks
      transmit Theileria species but the others transmit Babesia, Anaplasma and
      Eperythrozoon. The two latter ones can also be transmitted through some biting
      flies and mechanical means. Control methods presently available in Iran rely
      almost entirely on: (i) vaccination of sheep and goats with cell culture vaccine
      for theileriosis; (ii) chemotherapeutic treatment for babesiosis and
      anaplasmosis; (iii) acaricides for control of tick vectors.

PMID- 9530695
TI  - Conventional vaccines for tick-borne haemoparasitic diseases of sheep and goats.
AB  - Of the many tick-borne haemoparasites of sheep and goats, three may be controlled
      by vaccination. A live virulent blood vaccine for Cowdria ruminantium infection
      (heartwater) is used widely in southern Africa in an infection and treatment
      procedure. A live vaccine for Babesia ovis attenuated by passage in
      splenectomised sheep has been used extensively in Bulgaria with good results. A
      live vaccine for Theileria hirci, consisting of schizonts propagated in a
      lymphoid cell culture and attenuated by passage, has been used successfully in
      the Middle East.

PMID- 9530696
TI  - General review of the tick species which parasitize sheep and goats world-wide.
AB  - The paper lists the genera and species of ticks which occur world-wide in sheep
      and goats. The list is based on records documented in scientific ticks
      collections. Most ticks belong to Haemaphysalis, Rhipicephalus and Hyalomma
      genera which include many species with unclear taxonomic status and which are
      rather difficult to identify. The review points out that present knowledge on
      ticks which parasitize sheep and goats world-wide is still fragmentary.

PMID- 9530697
TI  - Subunit vaccines for the control of tick-borne diseases: implications for the
      future.
AB  - Tick-borne parasites are a major constraint to the improvement of livestock
      productivity in the developing world. These parasites include Theileria parva, T.
      annulata, Babesia bigemina, B. bovis, Anaplasma marginale and Cowdria
      ruminantium. The impact of these diseases is currently limited by the use of
      acaricides to decrease transmission by the tick vectors and immunization of the
      host animals using live vaccines. The use of acaricide is hampered by the
      development of acaricide resistance and live vaccines are dependent on cold chain
      facilities, which are generally unreliable in developing countries. There is
      therefore a requirement for improved vaccines that circumvent these problems.
      Candidate vaccine antigens have been identified for most of these parasites and
      are currently being evaluated for their capacity to induce solid protection.

PMID- 9530698
TI  - Ticks infesting sheep and goats in the Sudan.
AB  - Very little work has been carried out on ticks infesting small ruminants in the
      Sudan. Of some 70 tick species recorded in the Sudan, 34 species of different
      genera were collected from sheep and goats, two belonging to the genus Amblyomma,
      seven to the genus Hyalomma, 22 to the genus Rhipicephalus and three to the genus
      Boophilus. Nevertheless, their distribution, the seasonal abundance and
      population dynamics are poorly studied. Particularly, the peculiar distribution
      of A. lepidum and A. variegatum in the Nuba mountains needs further study. The
      variable climatic conditions of the country and the importance of the animal
      wealth in the national economy are all factors that call for more efforts to
      study the tick problem in this country.

PMID- 9530699
TI  - Major tick-borne diseases of sheep and goats in the Sudan.
AB  - Tick-borne diseases of sheep and goats have not been thoroughly investigated in
      the Sudan. Heartwater, the most important of the group, was reported only in the
      early '60s and malignant theileriosis of sheep in the mid '80s. Other tick-borne
      diseases of sheep and goats like anaplasmosis, Q fever, Nairobi sheep disease and
      babesiosis are expected to be present although the vector which transmit Nairobi
      sheep disease, Rhipicephalus appendiculatus is confined to a very narrow stretch
      on the Southern border with Zaire, Uganda and Kenya.

PMID- 9530700
TI  - Status of tick infestation of sheep and goats in Turkey.
AB  - Results of the identification and prevalence of ticks collected from 5,887 sheep,
      2,125 goats and 1,079 stables during the period of 2 years in Ankara and Elazig
      provinces, Turkey, are given together with a map showing the areas surveyed.
      Distribution of ticks in the provinces is reported as well.

PMID- 9530701
TI  - Status of the tick-borne diseases in sheep and goats in Turkey.
AB  - A serological survey using Indirect Fluorescent Antibody Test (IFAT) for Babesia
      ovis infection of sheep has been carried out in different geographical regions of
      Turkey. The results indicated that 71.6% of 141 sheep in Black Sea region, 70.9%
      of 93 sheep in central Anatolia, 80.2% of 96 sheep in Aegean region and 55.7% of
      122 sheep in eastern Anatolia were seropositive. This means that B. ovis
      infection is endemic throughout Turkey. In addition, occurrence of B. ovis, B.
      motasi, Theileria hirci, T. recondita and Anaplasma ovis infections in sheep and
      goats has been reported previously in Turkey as well. However further studies are
      needed to obtain more information about the agents to keep the infection under
      control.

PMID- 9530702
TI  - Sheep and goat tick management.
AB  - Tick and tick-borne disease (TBD) problems of sheep and goats are less well
      studied than those of cattle. Nevertheless, small ruminants are able to acquire
      worthwhile resistance to most tick species and the principles of enzootic
      stability and the need to preserve it are similar to those with cattle. In
      practice, sheep and goats are often grazed nomadically and initial TBD infections
      may be delayed. This may well account for losses from Nairobi sheep disease and
      heartwater. Sheep and goats are also affected by direct tick damage including
      tick bite abscesses, tick paralysis, tick-induced dermatophilosis, etc. Otherwise
      direct damage is believed to be only slight and stress from dipping causes
      reductions in liveweight gain greater than those caused by the ticks. Even "pour
      on" preparations produce no economic benefit in studied situations despite the
      lack of stress. A pragmatic approach to tick management is needed for varying
      situations although the need to preserve enzootic stability is of paramount
      importance.

PMID- 9530703
TI  - General review of tick-borne diseases of sheep and goats world-wide.
AB  - A general review of the tick-borne diseases of sheep and goats is given, with the
      emphasis on those thought to be of greatest economic importance. These include
      babesiosis, theileriosis, cowdriosis, anaplasmosis, ehrlichiosis, Nairobi sheep
      diseases and tick paralysis. A commented list of tick-borne diseases and their
      vectors is presented. It is stressed that large gaps remain in our knowledge of
      the real importance in the field of many of these diseases, especially in local
      stock.

PMID- 9530704
TI  - Synchronization, decrease in strength of pattern, illusory contours, and neon
      color effect.
AB  - When certain elements in a pattern are replaced by colored lines, a spreading of
      neon-like color can be seen around the lines. Using a variety of neon displaying
      patterns, we hypothesize that two conditions are critical to the neon effect. One
      is the occurrence of illusory contours and another a decrease in strength of
      pattern of the colored lines. On the basis of the two conditions, various
      phenomena of the neon effect are discussed. Finally, examining the striking
      characteristics of the neon effect, the vagueness of the colored lines and the
      spreading of the color of the colored lines over an illusory area wherein the
      color stimulus does not exist, we conclude that the neon effect is caused by
      synchronization of strength of pattern.

PMID- 9530705
TI  - Immediate versus remote judgements: delay of response and rate of stimulus
      presentation in time estimation.
AB  - A systematic replication of Vitulli and Shepard's 1996 study showed that a change
      in response requirements (verbal estimation) from circling time intervals on a
      scoring sheet in the older study to writing subjective time estimates in the
      present study did not alter the robust effects of a delay in retrospective
      judgement. A complete 2 x 2 x 2 factorial analysis of variance showed main
      effects for rate (fast versus slow) of stimulus (random digits, 1-5) presentation
      and delay of estimate (immediate versus remote), yet there were no interactions
      among rate, delay, or sex. The interpolation of "filler tasks" between the end of
      the target interval and subjective estimate of the duration of the target
      interval significantly increased perceived time compared to estimates made
      immediately after the target interval.

PMID- 9530706
TI  - Rehabilitation of visuomotor skills in poststroke patients using the Dynavision
      apparatus.
AB  - The Dynavision is a new apparatus that may help address some of the limitations
      inherent in conventional approaches to rehabilitation of visual skills of persons
      suffering from neurological dysfunction. Here the basic features of the apparatus
      are described, an overview of preliminary experimental evidence for its
      effectiveness in rehabilitation presented and application in the training of
      compensatory scanning strategies for visual inattention and visual-field deficits
      and in the increasing of oculomotor control outlined.

PMID- 9530707
TI  - Preference for musical tempo involving systematic variations of presented tempi
      for known and unknown musical excerpts.
AB  - Previous studies have indicated inconsistently that preferred tempo was moderate
      or fast. The basis for inconsistency might be differences in methods, i.e.,
      differences in tempo operation and subjects' experience of listening to musical
      pieces. The present study examined the preference for tempo using known and
      unknown melodies which were presented at varied tempi systematically. 119
      undergraduates not majoring in music were subjects, divided into three subgroups,
      slow, medium, and fast music groups according to tempi designated by composers.
      Subjects rated items about Perceived Activity and affect for each stimulus
      presented at varied tempi. Subjects evaluated fast tempi as active regardless of
      differences in the designated tempi and prior listening experience. Affect
      (including preference) showed an inverted-U shape relationship to variations in
      tempo. The most preferred tempo was the designated tempo for known melodies,
      while moderate tempi (109 to 130 in metronome measure) were preferred for unknown
      melodies.

PMID- 9530708
TI  - Eliminating temper tantrums in a four-year old by parents eliciting incompatible
      behavior.
AB  - A 4-yr. old boy's temper tantrums were modified by eliciting incompatible
      behavior. Family dynamics changed to more acceptance of the child's decision
      making and attention needs.

PMID- 9530709
TI  - Word Association Test and psychosexual cues in assessing persons with eating
      disorders.
AB  - The present study aimed to detect psychosexual conflicts in patients with eating
      disorders using the Word Association Test which tests the perceptual sensitivity
      of the subject to conflictual words. We also expected patients to show concern
      about food and eating. 19 anorexic patients, 21 bulimic patients, and 20 control
      subjects without eating disorders provided associations to four groups of words:
      psychosexual words, food words, emotionally loaded words, and neutral words.
      Reaction times were recorded. Analysis showed that anorexic patients were slower
      than controls in responding to food-related words but bulimic patients were not
      significantly different from controls. Anorexic patients reacted more slowly than
      controls to psychosexual words. Bulimic patients were also somewhat slower than
      controls but faster than anorexic patients; however, these differences were not
      statistically significant. Results are congruent with research that points to
      sexual problems and delays in the psychosexual development of anorexic patients
      and to a lesser extent of bulimic patients.

PMID- 9530710
TI  - Psychological skills in basketball: preliminary study for development of a Greek
      form of the Athletic Coping Skills Inventory-28.
AB  - The purpose of this preliminary study was to examine for a sample of 126
      basketball players the psychometric properties of a Greek version of the 1995
      Athletic Coping Skills Inventory-28 by Smith, Schutz, Smoll, and Ptacek. A
      confirmatory factor analysis supported the structural validity of the translated
      inventory. Moreover, six of the seven subscales showed adequate internal
      consistency. The discriminant validity of the scores on the inventory was
      supported by examining mean differences between experienced and inexperienced
      athletes as well as between athletes of different levels of competition. Further
      steps for the validation of the inventory in Greek are discussed.

PMID- 9530711
TI  - Caffeine ingestion and performance.

PMID- 9530712
TI  - Assimilation and contrast in awareness.
AB  - Assimilation and contrast (context-produced increases and decreases in sensed
      similarity) in awareness may be basic to understanding vision, audition,
      cognition, and memory. Key considerations follow.

PMID- 9530713
TI  - Visual search, reaction time, and cognitive ability.
AB  - The contributions of visual search to reaction time and cognitive ability were
      investigated with 45 subjects. Visual search was assessed via eye movements. The
      electrooculogram was recorded while a subject located letters arranged in a large
      display. Reaction time was obtained for a search task. A reasoning and a space
      scale served to assess cognitive ability. Substantial correlations of number,
      amplitude, and velocity of saccades with reaction time were obtained. Significant
      correlations of scores on ability scales with reaction times and amplitudes of
      saccades were also observed. Obviously, subjects of higher ability showed
      amplitudes better adjusted to the distances between the letters than those of
      lower ability.

PMID- 9530714
TI  - Use of hypnosis and Jacobson's relaxation techniques for improving academic
      achievement of college students.
AB  - This study of group hypnosis and Jacobson's muscle relaxation techniques
      evaluated change in academic examination grades of undergraduate students in
      educational psychology. An intact group of 30 students who were hypnotized were
      compared over 15 weeks with a class of 22 students given muscle relaxation
      instruction. Although initially scores were similar, the former group had
      significantly higher mean scores on the final examination than the latter. Some
      suggestions for further study are made.

PMID- 9530715
TI  - Paraprofessionals' attitudes toward inclusion of students with disabilities in
      physical education.
AB  - The Physical Educators' Perceptions of Inclusion Inventory was administered to 80
      paraprofessionals in special education. A Mann-Whitney U analysis indicated a
      significant difference in scores on knowledge related to inclusion by years of
      experience working. There was a significant difference between knowledge scores
      for length of time working but none for scores on perception.

PMID- 9530716
TI  - Construction of validity scales for the Multiple Affect Adjective Check List
      Revised.
AB  - Three scales, the Fake Bad Scale, the Fake Good Scale, and the Fake Bad-Fake Good
      scales were developed and evaluated with respect to their capacity to detect
      response manipulation on the Multiple Affect Adjective Check List-Revised.
      Cutting scores for each scale were cross-validated in two samples consisting of
      three groups: (1) college students simulating either "fake good" or "fake bad,"
      (2) college students under standard instructions, and (3) psychiatric patients.
      Cutting scores on the three scales were compared with cutting scores established
      for the MAACL-R Dysphoria and Positive Affect plus Sensation Seeking. Analysis
      indicated that these scales were more accurate than the Positive Affect plus
      Sensation Seeking and the Dysphoria scales in detecting response manipulation.

PMID- 9530717
TI  - Height, weight, and body fat: assessments of covariation based on visual
      information or reported correlations.
AB  - College students' intuitive judgments about covariations between height, weight,
      and body fat were assessed in three experiments using responses to a series of
      propositional statements as the dependent variable. In Exp. 1, judgments were
      rendered without explicit exposure to a prior database. In Exps. 2 and 3,
      however, databases were studied prior to these judgments. Remarkable
      consistencies in judgments of weight and body fat, height and weight as well as
      of height and body fat were obtained across experiments. At best, there was
      little evidence that the databases influenced the judged covariations among these
      variables. Whereas judgments about weight and body fat were unambiguous and
      consistent with the actual positive correlation between weight and body fat,
      judgments about height and weight as well as height and body fat were less
      clearcut. What was clear, however, was that these judgments were highly similar.
      Implications of these findings from previous research that suggest that presence
      of a perceived negative correlation between height and body fat are discussed.

PMID- 9530718
TI  - Effects of a movement and swimming program on water orientation skills and self
      concept of kindergarten children with cerebral palsy.
AB  - In this study the effect of an experimental movement and swimming program of six
      months on motor function in the water measured by means of the Water Orientation
      Score and self-perception measured by means of the Martinek-Zaichkowsky Self
      concept Scale was investigated. 23 children participated in the program,
      completing both tests prior to and after the intervention. An age-, sex-, and
      disability-matched control group of 23 children completed only the Self-concept
      Scale at pre- and posttest. Analysis indicated a significant improvement in Water
      Orientation Score of children in the trained group, but no effect on scores of
      the Self-concept Scale.

PMID- 9530719
TI  - A grade four reading level key for the Multiple Affect Adjective Check List
      Revised.
AB  - Data from samples of College Students (n = 433), Adolescents (n = 746), and a
      community mental health center sample (Outpatients) (n = 202) were rescored using
      a scoring key that consisted of adjectives from the Multiple Affect Adjective
      Check List-Revised at or below the Grade 4 reading level (MAACL-R4). Factor
      analyses showed that, unlike the MAACL-R, a three-factor structure (Positive
      Affect 4, Anxious Depression 4, and Hostility 4) best described the 38 Grade 4
      adjectives on the MAACL-R4. Estimates of reliability (internal consistency and
      test-retest) for each scale were acceptable. Correlations between scores on MAACL
      R4 and four Self-rating Mood Scales showed expected convergent and discriminant
      validities. Also, patterns of means among the three groups could differentiate
      the nonreferred from referred samples.

PMID- 9530720
TI  - Time-series studies of the French suicide rate using age-adjusted rates.

PMID- 9530721
TI  - Masking effect of motivation on ultradian rhythm.
AB  - To test the masking effect of motivation on ultradian fluctuations in arousal, we
      examined the self-rating scores for sleepiness, fatigue, and motivation and the
      electroencephalographic data for 5 male university students (age range, 18 to 20
      years). They watched either an animated video series (Animation condition)
      intended to enhance motivation or interest or a landscape video series (Landscape
      condition) intended to induce lack of interest due to boredom. Each subject
      watched the two series for more than one week in a 3.1 x 3.1 m isolation unit.
      Each series was presented for 12 min. every 20 min. from 0900 to 1800. Subjective
      sleepiness and fatigue increased, and motivation was decreased for Landscape
      condition, suggesting the validity of the experimental manipulation. Closed-eye
      Oz-EEG alpha and beta activities fluctuated in an ultradian manner for both
      conditions, although slower cycles were observed at an interval of the Animation
      condition. The coefficients of variation of time series data were also lower for
      the Animation condition. These data suggest that either high motivation or
      absence of sleepiness or fatigue mask ultradian arousal cycles by producing fewer
      or slower fluctuations.

PMID- 9530722
TI  - Cutaneous and psychosocial benefits of alpha hydroxy acid use.
AB  - Alpha hydroxy acids are used extensively by patients and consumers for
      restorative cutaneous purposes. The current study of 32 patients evaluated the
      clinical and psychosocial effects of this cosmetic therapy. After 12 weeks,
      significant clinical improvements were found for facial skin tone and fine
      wrinkling, as well as for patient-reported satisfaction with physical appearance
      and with marital or relationship quality.

PMID- 9530723
TI  - A mediational model of social physique anxiety and eating disordered behaviors.
AB  - In the present study correlations among scores on social physique anxiety, social
      behavior inhibition, and eating disordered behaviors and traits were hypothesized
      on the basis that social physique anxiety would be correlated with personality
      disturbances associated with eating disorders and mediated by social inhibition
      and eating disordered behaviors. Subjects were 79 college-aged women (M age =
      19.5 yr.), who completed the Garner's Eating Disorders Inventory, the Social
      Physique Anxiety Scale, and a measure of social behavior inhibition developed for
      this study. A mediational path analysis showed scores on social physique anxiety
      significantly moderately related to scores for eating disordered traits, mediated
      by scores on eating disordered behavior. These correlations account for 14 to 31%
      of the common variance, and with clinical research, support the assumption that
      eating-disordered behavior may begin with milder symptomatology such as high
      scores on social physique anxiety. Longitudinal research is required to assess
      the proposed causal relationship between identification of early symptoms and
      later eating disorders; however, present research suggests early intervention
      with women at risk may be useful.

PMID- 9530724
TI  - Development of psychological aspect in pursuit eye movements among preschoolers.

PMID- 9530725
TI  - Laboratory studies of a sound system that maintains wakefulness.
AB  - Two studies investigated the effects of a waking sound that enhances wakefulness.
      Study I investigated the effect of the sound level and Study 2 the effect of time
      and frequency variability of the sound. The recordings of EEG and subjective
      ratings were analysed to study the effect upon wakefulness. The waking effect
      increased when sound varied in duration and frequency. A number of specific
      conditions necessary for the waking effect are described. The exposure should be
      based on high frequency sounds and several tones chosen to produce disharmony.
      The exposure should be loud enough to be heard over the masking background noise.
      The duration and tonal quality should be variable from one presentation to
      another.

PMID- 9530726
TI  - Modifications of body-image induced by virtual reality.
AB  - In contrast to the great number of publications on body image, only a few papers
      have focused on the treatment of a disturbed body image. In general, two direct
      and specific approaches are usually used, a cognitive/behavioural therapy to
      influence patient's feelings of dissatisfaction and a visuomotor therapy with the
      aim of influencing bodily awareness. The aim of this study was both to develop a
      virtual reality environment integrating the two approaches and to test its
      efficacy on a nonclinical sample of 24 women. Before and after a 10-min. virtual
      experience all the subjects made ratings on the Figure Rating Scale and the
      Contour Drawing Rating Scale. Analysis showed a significant reduction in body
      dissatisfaction without any major side effect.

PMID- 9530727
TI  - A longitudinal study of visuospatial discrimination in parkinsonian patients.
AB  - Visuospatial discrimination was evaluated longitudinally in 45 patients with
      idiopathic Parkinson's disease. 47 normal matched subjects served as controls.
      Visuospatial discrimination was assessed by means of a picture test with complex
      superimposed objects (Poppelreuter's test) at the beginning of the study as well
      as three years later. At initial evaluation the group with Parkinson's disease
      identified fewer objects than the control group and made more errors. Relations
      between performance on the visuospatial discrimination task and the main
      parameters of the disease were not statistically significant. At reevaluation,
      three years later on the same task, performance by the group with Parkinson's
      disease deteriorated. Longitudinal assessment of motor symptoms showed that
      disease progressed during the study period in 35 patients. Comparison of motor
      deterioration with performance on the visuospatial discrimination task showed no
      statistically significant relationship.

PMID- 9530728
TI  - Assessment of pain: a survey of practicing clinicians.
AB  - This study reports on use of tests in the assessment of pain patients. Data are
      based on 212 respondents from the Society of Behavioral Medicine. Personality
      inventories, measures of depression and anxiety, coping scales, and the McGill
      Pain Questionnaire were among the top 10 ranked instruments.

PMID- 9530729
TI  - Perception of physical exertion during dynamic exercise: a tribute to Professor
      Gunnar A. V. Borg.
AB  - A review of the physiological validation and some clinical applications of G. A.
      V. Borg's measure of perceived exertion for a range of physical activities and
      settings illustrates the widely generalized base of Dr. Borg's experimental
      findings and scientific insight.

PMID- 9530730
TI  - Reading achievement by learning disabled students in resource and regular
      classes.
AB  - K-TEA Comprehensive Reading scores of 34 elementary boys in either resource rooms
      or regular settings were compared. The boys were identified as learning disabled
      in reading. They were pretested at the beginning of the school year and
      posttested at the end. Treatment was one year of daily instruction in reading
      provided by six teachers in resource setting and six teachers in regular
      settings. K-TEA Reading Decoding and Reading Comprehension scores, separately
      compared in 2 x 2 repeated-measures analysis of variance, were not significantly
      different.

PMID- 9530731
TI  - Concurrent validity of the Koppitz Bender-Gestalt emotional indicators among
      women with mental retardation.
AB  - This study evaluated the concurrent validity of Koppitz' revised Bender-Gestalt
      Emotional Indicators among 44 women with mental retardation. The concurrent
      validity of the Emotional Indicator total score was not supported when compared
      with responses on two widely used and accepted screening inventories, the Reiss
      Screen and the Inventory for Client and Agency Planning.

PMID- 9530732
TI  - Ratio of male and female characters in a dream series.
AB  - The present study investigated the change in gender ratio of dream characters in
      relation to the dreamer's environment in waking-life and found a preponderance of
      male characters in the subject's dream while living in a 'male' environment which
      was not present while living in a 'female' environment. The results support the
      continuity hypothesis of dreaming and stress the importance of situational
      factors rather than personality factors in the explanation of the gender ratio of
      dream characters.

PMID- 9530733
TI  - Crossing the midline: a study of four-year-old children.
AB  - Midline crossing refers to behavior that results in reaching, stepping, or
      looking, across the body's midline. Several studies have indicated that infants,
      young children, and individuals with disability make more errors on midline
      crossing tasks than on similar tasks placed at the ipsilateral side. Until
      recently, assessment of midline crossing has used a spatial protocol and has been
      criticized for not having a temporal component. The purpose of this study was to
      assess midline crossing by 9 4-yr.-old children within an information processing
      context. Analysis indicated that contralateral tasks required more processing
      time than similar tasks placed ipsilaterally.

PMID- 9530734
TI  - Preference for sex of first child among women classified as androgynous and
      nonandrogynous.
AB  - This paper examined the relation between gender-role orientation and the
      preference for sex of firstborn child in 212 pregnant nulliparous women. The Bem
      Sex-role Inventory was used to assess gender-role orientation of participants.
      Analysis suggested that gender-role orientation, as measured does not effectively
      predict the preference for sex of firstborn child.

PMID- 9530735
TI  - Scratch density differentiates microsmic from normosmic and anosmic subjects on
      the University of Pennsylvania Smell Identification Test.
AB  - During assessment of smell function using the University of Pennsylvania Smell
      Identification Test, we observed that some persons with diminished smell
      perception seemed to perserverate in their attempts to release the odorant from
      the microencapsulated odorant strips. In this study we quantified the marked area
      of 1680 such strips from tests administered to 42 anosmics, normosmics, and
      microsmics. The density of pixels on the microencapsulated labels from the
      microsmic patients was greater than that from the other two groups, which did not
      differ significantly from one another. These data suggest (i) that persons with
      diminished olfactory ability attempt to increase the perceived intensity of the
      stimulus by marking the test's scent strips more vigorously and (ii) that the
      density of such marking may prove useful in detecting malingerers attempting to
      feign microsmia.

PMID- 9530736
TI  - Increasing return rates of a mail survey to exercise professionals using a modest
      monetary incentive.
AB  - This study indicated that a variety of survey techniques resulted in a modest
      return rate (66%) in a national survey of 455 exercise professionals. A $1.00
      bill incentive was significantly more effective than no incentive in improving
      returns, and the rate of double responses in this anonymous mail survey was
      extremely low (< 1%).

PMID- 9530737
TI  - What makes dreams positive or negative: relations to fundamental dimensions of
      positive and negative mood.
AB  - The present study examined the general emotional content of dreams reported by
      individuals who typically experience "positive" versus "negative" dreams. Self
      reports of the 153 participants indicated that positive versus negative dreamers
      (ns = 42 and 24, respectively) generally experienced more positive emotions,
      e.g., joviality, self-assurance, and fewer negative emotions, e.g., fear,
      sadness. No differences were found in the self-reports of the participants in the
      experience of surprise, guilt, fatigue, and shyness between the groups, hence,
      positive and negative dreams do not appear to reflect simply more positive and
      fewer negative emotions, respectively.

PMID- 9530738
TI  - Partial cross-validation of low correlation for scores on the Test of Visual
      Motor Integration and the Beery-Buktenica Developmental Test of Visual-Motor
      Integration.
AB  - The aim of this study was to further investigate the correlation between a well
      established test, the Beery-Buktenica Developmental Test of Visual-Motor
      Integration and a new copying test, the Test of Visual-Motor Integration. For
      scores on the tests of 71 children from a public school in Italy, the correlation
      is .34, which is consistent with earlier evidence and indicates that the Test of
      Visual-Motor Integration is not a substitute for the Beery-Buktenica
      Developmental Test of Visual-Motor Integration.

PMID- 9530739
TI  - The Verbalizer-Visualizer Questionnaire: a review.
AB  - The psychometric properties of Richardson's 1977 Verbalizer-Visualizer
      Questionnaire have been studied by analyzing papers in which this questionnaire
      was employed. Such review showed that the Verbalizer-Visualizer Questionnaire
      does not measure a unidimensional construct and does not predict the actual use
      of mental imagery in thinking. Further, a lack of long-term reliability of the
      questionnaire emerged. In conclusion, use of the questionnaire to assess the
      verbal-visual cognitive style appears questionable.

PMID- 9530741
TI  - Use of dohsa-hou, a Japanese psychorehabilitative program, to guide motor
      activity of young adults with cerebral palsy.
AB  - Dohsa-hou, a Japanese psychorehabilitation method for motor training, was
      introduced to 10 subjects with cerebral palsy in a pre-post (6-wk.) design. Four
      expert raters were asked to judge the improvement in range of motion, ease and
      smoothness of movement, correctness of posture) of these subjects. Findings
      suggest that the training method had a significant effect on body movement as
      compared to body posture. Since the effect may be peculiar to this subject group,
      further studies are suggested.

PMID- 9530740
TI  - Elevations of complex partial epileptic-like experiences during increased
      geomagnetic activity for women reporting "premenstrual syndrome".
AB  - Responses to the frequency of complex partial epileptic-like experiences were
      recorded every second day by 12 women for at least two months per individual.
      Five (41%) of the women displayed significant increases (effect sizes between 6%
      and 17%) in the numbers of these experiences when the daily geomagnetic activity
      exceeded 40 nT. The results were consistent with the hypothesis that a spectrum
      of experiences and behaviours, associated with limbic lability, can be enhanced
      by environmental stimuli correlated with perturbations of the geomagnetic field.

PMID- 9530742
TI  - Projected animal preferences in incarcerated and nonincarcerated men.

PMID- 9530743
TI  - A defensive response set and the relation between cognitive and emotional
      functioning: a replication.
AB  - This study was designed to examine the hypothesis that a defensive self-report
      response set tends to attenuate the strength of the relationship between self
      reported emotional functioning and cognitive tests, particularly the functioning
      of verbal memory. 75 patients with end-stage lung disease were administered the
      MMPI and a cognitive test battery as part of a psychosocial evaluation for
      transplantation. Patients were separated into defensive and nondefensive groups
      using the MMPI F - K Gough Dissimulation index (raw score F minus K < or = -15).
      Cognitive factor scores were generated and correlated with non-K-corrected raw
      scores of MMPI Scales 2, 7, and 8. Correlation coefficients were compared across
      groups. As predicted, increases on Scales 2 and 7 were significantly associated
      with decreased functioning of verbal memory (r = -.35 and -.34, respectively)
      among the nondefensive group but were unrelated in the defensive group. It is
      argued that the attenuation of the relationship between self-reported emotional
      status and verbal memory functioning is, in part, due to a restricted range of
      symptom endorsement on the MMPI among the defensive group. These findings
      replicate those previously reported using a sample of patients with cardiac
      disease.

PMID- 9530744
TI  - Survey of commercial airline pilots' hearing loss.
AB  - 64 commercial airline pilots (ages 35-64 yr, Mdn: 53) were surveyed regarding
      hearing loss and tinnitus. Within specific age groups, the proportions responding
      positively exceed the corresponding proportions in the general population
      reported by the National Center for Health Statistics.

PMID- 9530745
TI  - Some aspects of earedness--the validity and reliability of self-report items.
AB  - In contrast to the extensive literature on hand, foot, and eye preferences there
      are only a few studies concerning ear preference. From a review of 27 studies 13
      items (Stopwatch, Telephone receiver, Tablecloth, Head movement, Wall, Drawer,
      Wall phone, Heartbeat, Door, Earphone, Box, Pocket radio, Voice) were identified
      in the measurements of ear preference. In a series of investigations, these self
      report items were validated with respect to individual behavioural measures and
      test-retest reliabilities were obtained over 1 mo. and 1 yr. for earedness. These
      data indicate that a questionnaire composed of these items could be a valid and
      reliable method for the assessment of various forms of ear preference, but there
      are several differences among the items in validity and reliability.

PMID- 9530746
TI  - The 24-hour variation of mood differs between morning- and evening-type
      individuals.
AB  - This study investigated a 24-hour variation of subjective mood in 16 healthy
      Morning-type and 13 Evening-type subjects as defined by the time of day at which
      their oral temperature curve reached its maximum. The subjects were instructed to
      use a sleep-wake logbook, in which they kept daily records of the ratings of
      their mood and alertness for a period of two consecutive weeks. For mood as well
      as for alertness analysis of variance indicated significant interactions between
      Morning and Evening-types and time of day. It is concluded that a pronounced
      diurnal variation of mood can be observed in healthy individuals, which differs
      between Morning-type and Evening-type subjects.

PMID- 9530747
TI  - Moving around objects and recognizing them.
AB  - This research concerned the use of mental rotation in recognizing rotated
      objects. Instead of the classic Shepard's paradigm in which subjects were still
      while observing rotated objects, here subjects had to move (or imagine moving)
      around stationary three-dimensional objects put in the middle of the trajectory.
      Thus, depending on the viewing positions, such objects were seen under six
      different perspectives (from 30 degrees to 180 degrees). The latter task has been
      thought to be closer to everyday life in which we obtain information regarding
      objects from their spatial properties. The results do not follow the classic
      rules of mental rotation of an object predicting a linear increase of the time
      needed to recognize distorted objects as a function of their angular
      displacement. They also differ from data in the literature about spatial imagery
      showing that access to spatial information is facilitated more when people
      actually move through a path than when they imagine moving. A probable
      explanation of this difference from the literature is discussed in relation to
      the particular involvement of the body in the experimental task.

PMID- 9530748
TI  - Ratings of perceptions related to phenomenological theory.
AB  - 94 participants were asked to give their opinions about people on four issues
      relevant to the personality approach posited by phenomenological theorists.
      Participants generally appeared to express a more negative view of others'
      characteristics such as "goodness" than the position espoused by the theorists.

PMID- 9530749
TI  - An exploratory study of perceptual-motor abilities of women: novice and skilled
      players of team handball.
AB  - Comparisons of ability between skilled performers and novices have been made for
      activities such as basketball, volleyball, tennis, squash, and badminton, but
      there is little work on team-handball which is not a well-recognized sport in
      North America. To examine a variety of perceptual, e.g., anticipation time,
      reaction time, and motor, e.g., throwing tasks, abilities of skilled and novice
      female team-handball players 13 First Division (skilled) and 10 recreational
      (novice) players (M age = 25.3 yr.) performed 2 laboratory activities (for
      measurement of anticipation time, reaction time and movement time) and 3 field
      tasks (for measurement of accuracy and speed of throwing abilities) in random
      order. Reaction time and movement time were collected during a unique team
      handball motor activity. Analyses of variance with repeated measures on trial
      blocks indicated high mean proficiency for the skilled participants in reaction
      time and all field-throwing tests compared with the novice participants. These
      reliable differences in team-handball activities further support superiority in
      sport settings gained by physical achievements and psychomotor excellence. In
      other words, skilled female team-handball players threw faster and more
      accurately and responded more rapidly than novice players.

PMID- 9530750
TI  - Childrens' perceptions of parents' and peers' behavior.

PMID- 9530751
TI  - Relation of visual perception and visual-motor integration for clumsy children.
AB  - The purpose of this study was to examine the relationship between visual
      perception and visual-motor integration in 30 normal children compared to 30
      clumsy children. Difficulty in visual perception, as assessed by the Test of
      Visual-Perceptual Skills, accounts for about half the variance in the clumsy
      children's performance in visual-motor integration, as assessed by the
      Developmental Test of Visual Motor Integration. In contrast, the correlation
      between scores on these tests for normal control children was low and not
      significant. These results suggest that visual perception and visual-motor
      integration may be separate functions in normally developing children. When
      considering clumsy children, however, these functions cannot be considered as two
      independent skills.

PMID- 9530752
TI  - Perceptual integrations and the "normal" Rorschach percept.
AB  - The "normal" Rorschach percept is characterized by congruency (correspondence
      between blot and reality) and good form (an appropriate synthesis among elements
      comprising the blot). Both congruency and good form arise from perceptual
      integrations and can be objectified in terms of providing false information
      (incongruency) and maximizing identifying information about the blot (good form),
      thus providing a logical foundation for Rorschach interpretation.

PMID- 9530753
TI  - Cyclical calendar and lunar patterns in automobile property accidents and injury
      accidents.
AB  - Nine years of traffic accidents involving damage to property (n = 246,926
      accidents) and involving nonfatal injury (n = 50,492) in Saskatchewan were
      examined by regression and spectral analyses. Both calendar and seasonal
      periodicities were found in both sets of data. After data were adjusted for
      calendar effects, no relationship was found with the total or half synodic and
      anomalistic lunar cycles or between the waxing and waning synodic cycle. No
      sudden change on the day of the full moon or surrounding days was found.

PMID- 9530754
TI  - Inventory-derived task handedness preferences of nine professions and their
      associations with self-report global handedness preferences.
AB  - The handedness preference (laterality) of 1,196 professionals grouped in nine
      professions previously reported using self-reported global handedness and scores
      on a modified Edinburgh Handedness Inventory was further defined by evaluating
      the association between profession and the 10 manual tasks of the inventory. The
      previously reported ranking of professions in order of increasing righthandedness
      of laterality score arose from the handedness of specific inventory tasks. A
      similar association was found for self-reported global handedness. The evidence
      continues to support the hypothesis of an association between handedness
      preference and specific aptitudes or skills in this sample of professional
      persons.

PMID- 9530755
TI  - Assessment of children and youth from culturally and linguistically diverse
      backgrounds with mental chronometric techniques.

PMID- 9530756
TI  - Motivational climate and intrinsic motivation of young basketball players.
AB  - The present study examined the relationship between motivational climate with
      intrinsic motivation for athletes with high and low perceived competence. It was
      predicted that for highly competent athletes a motivational climate of high
      mastery and high performance would be associated with enhanced intrinsic
      motivation whereas for athletes of low competence perceptions of a motivational
      climate of high mastery would be associated with higher intrinsic motivation.
      Analysis for 100 male basketball players showed that there was no significant
      interaction between perceived competence and perceptions of motivational climate.
      Scores for perceptions of a task-involving climate were significantly correlated
      with intrinsic motivation.

PMID- 9530757
TI  - Constraints on grip-selection: minimizing awkwardness.
AB  - In picking up and manipulating an object, the selection of an initial grip
      (overhand versus underhand) often depends on how comfortable the hand and arm
      will be at the end of the movement. This effect has been called "end-state
      comfort" and seems to be an important constraint in grip-selection. The present
      experiment further explored this effect by selecting a task that would ensure a
      comfortable ending position regardless of the initial choice of grip. 206
      undergraduates picked up a cardboard paper-towel roll from a horizontal position
      and placed one end down on a table. Analysis showed a clear preference for the
      overhand grip, as 78% of the participants chose this grip. In addition, more
      women preferred the overhand grip than men. The findings indicate that people may
      be sensitive to minimizing awkwardness in both terminal and initial positions.

PMID- 9530758
TI  - How limited is the unconscious? A brief commentary.
AB  - This report discusses the problems associated with the prevailing view that the
      province of unconscious influence is highly restricted. It is argued that present
      empirical data neither strongly support nor argue against a circumscribed notion
      of the unconscious.

PMID- 9530759
TI  - Impression formation as a function of male baldness.
AB  - A computer-morphing procedure was used to produce a "full cranial hair"
      photograph for comparisons of perceptions by 96 undergraduates of a photograph of
      a naturally bald 30-yr.-old man on 13 dependent measures derived from 30 semantic
      differential scales. Analysis showed the full-hair condition was rated
      significantly more dominant, dynamic, and masculine than the bald condition.
      While the model was also perceived as younger in the full-hair condition, there
      was no difference in mean ratings of attractiveness between photographs.

PMID- 9530760
TI  - [On the death of Karl-Peter Kisker].

PMID- 9530761
TI  - [The disease "picture" of schizophrenia. Change due to operational diagnostic
      systems and effects on research in epidemiology and disease course].
AB  - Both in classical German psychiatry and in the contemporary operationalized
      diagnostic systems schizophrenia is conceptualised as a categorical disorder, the
      presence or absence of which can be verified dichotomously. Empirical results,
      however, suggest that schizophrenia might be a dimensional disorder. The
      categorical perspective has advantages for epidemiological research; it produced
      important results like the finding of a world-wide equal incidence of
      schizophrenia. Increasing importance is attributed to the definition of criteria,
      especially those of duration, which is arbitrary in many aspects. Results of
      research concerning the course of illness and sex distribution vary, depending on
      the definition of criteria, giving rise to different etiological hypotheses.

PMID- 9530762
TI  - [What do you associate with the word schizophrenia? A study of the social
      representation of schizophrenia].
AB  - This study addresses the social representation of schizophrenia. The analysis is
      based on a representative survey among the population of the former East German
      provinces now reunified with formal West Germany as the new "Lander" of the
      Federal Republic, as well as on a survey among medical students at the
      Universities of Vienna and Leipzig. For those questioned, the most striking
      feature of schizophrenia was that of a "split" personality. In this context they
      assumed the parallel existence of two (or more) personalities in the sense of a
      multiple personality disorder. This metaphor is interpreted as the result of a
      concretisation process which is substantially supported by the representation of
      people with mental illness in literature and the media.

PMID- 9530763
TI  - [Schizophrenia in the "New Zurich Newspaper". A media analysis].
AB  - Social representations of mental illness and psychiatry are largely influenced by
      mass media. This study explores the use of the term "schizophrenia" in the Swiss
      newspaper NZZ in 1994 and 1995, the text of which is available on CD-ROM. In 31%
      of the cases the term is used figuratively, i.e. as a metaphor. When used as a
      name of an illness, it reflects contradictory connotations: schizophrenics as
      mentally ill offenders or criminal in the local columns, schizophrenics featuring
      as creative writers or artists in the cultural columns. Information on
      schizophrenia as disease is rare. If it does occur, reporting is rather
      sociopsychiatric than neurobiological.

PMID- 9530764
TI  - [Initial hospitalization of schizophrenic patients. Illness manifestations,
      stresses, problems and resources].
AB  - PURPOSE: In this study we examined subjective views other than the usually
      studied quality of life, needs and treatment satisfaction, of first-admitted
      schizophrenic patients. METHODS: Data of 90 patients were gathered with two
      established and a new questionnaire. RESULTS: Signs of anxious unrest and loss of
      vigour are the most frequently reported complaints in patients as well as in a
      sample of the Berlin general population that was also studied but with a clearly
      higher incidence in the patients. Patients are most often burdened by concerns
      regarding their disease and their objective living conditions, especially work.
      They experience social contacts and leisure activities as helpful. CONCLUSIONS:
      The findings suggest that complaints, burdens, worries and the fear of negative
      consequences--rather than being an expression of specific schizophrenic symptoms-
      are a non-specific reaction to a difficult and burdensome situation. In clinical
      practice, special consideration of this reaction and of the social conditions
      seems useful.

PMID- 9530765
TI  - [Medication-related attitudes of chronic schizophrenic patients. A follow-up
      study after psycho-educational intervention].
AB  - OBJECTIVE: To evaluate the effect of a psychoeducational training, compliance,
      medication management, and illness-related attitudes were assessed among
      schizophrenic outpatients. METHODS: Study patients who attended at least 70% of
      10 psychoeducational sessions (n = 74) and the 57 patients of the control group
      were reexamined 2 years after the end of intervention. RESULTS: Attenders had
      better compliance, were more confident in medication codetermination and more
      satisfied with their knowledge about medication. Confidence in medication and
      physician increased whereas in the control both decreased. CONCLUSIONS: Although
      there were no statistically significant differences the results show impressive
      longterm effects of psychoeducational training.

PMID- 9530766
TI  - [Family therapy as a component of routine management of schizophrenic patients. A
      report of experiences].
AB  - Since 1993 we have been working with nine groups of relatives of schizophrenic
      patients who were admitted as inpatients to two different psychiatric wards at
      the Landesklinik Nordschwarzwald. We summarise our experience with the family
      groups as a part of the psychiatric care for schizophrenic patients. The concept
      of family groups combines psychoeducational aspects with the concept of
      "Expressed Emotion". The relatives valued the combination of information,
      discussion and exchange of experiences positively. The groups offer relief and
      support. The involvement of the relatives has proved useful in the treatment of
      schizophrenic patients at our institution and will be continued. Further studies
      designed to improve the efficiency and quality of family groups will be important
      for their general establishment in psychiatric care.

PMID- 9530767
TI  - [Occupational integration of schizophrenic patients under current treatment
      conditions].
AB  - A cross-sectional study was carried out in Gottingen, Germany, including 100
      schizophrenic patients mostly under outpatient treatment. Data were collected
      concerning the course of the illness, the premorbid and present living
      circumstances and the self-assessment of those. The average age of the patients
      (42 female, 58 male) is 38 years, 82% are living without a partner. About one
      third are chronically ill, another third relapse frequently or suffer from
      residual symptoms. 84% take neuroleptic medication on a regularly basis. At first
      manifestation of the illness 84% are employed or undergoing vocational training.
      After a mean illness duration of 11 years only 34% of the patients are employed
      on the general or the sheltered labour market. The financial situation is closely
      connected with the vocational integration of the patients. 43% have a monthly
      income of less than DM 1000.-(645 US$) and 69% do have an income of less than DM
      1500.-(967 US$) per month.

PMID- 9530768
TI  - [Total illness costs of schizophrenia and monetary evaluation of prevention of
      recurrence exemplified by a standard depot neuroleptic (flupenthixol decanoate)].
AB  - Treatment of patients suffering from schizophrenia is very expensive. However, by
      consistently and methodically performed medical prophylaxis the disease can be
      controlled sufficiently well. Regular prophylactic treatment compared to repeated
      treatment of acute episodes has both medical advantages and reduces cost by
      reducing the rate of hospitalisation. Prophylactic treatment with
      Flupentixoldecanoat can save up to 68% of costs.

PMID- 9530769
TI  - [Schizophrenia simplex, schizotypal disorder and compulsions. Differential
      diagnostic considerations].
AB  - We report on the case of a man, whose psychopathological symptoms markedly varied
      during different phases of his illness, causing difficulties in applying common
      diagnostic criteria for schizophrenia. Depending upon each of the predominant
      symptoms, this resulted in different diagnoses and therapeutic strategies. We
      also discuss the importance of obsessions and compulsions in differential
      diagnosis in this case.

PMID- 9530770
TI  - [Acute water intoxication as a complication of therapy refractory schizophrenia].
AB  - A patient with chronic paranoid schizophrenia with delusions of infestation and
      of grandeur type, developed polydipsia in the course of his illness which ended
      up in acute life-threatening water intoxication. Apart from somatic causes like
      SIADH, which are discussed in literature, water-intoxication could
      psychodynamically be interpreted in the sense of acting on delusions.

PMID- 9530771
TI  - [The magic of the impact--exposing a phenomenon].

PMID- 9530772
TI  - [Chronic inflammatory bowel diseases. Pathophysiology and drug therapy].
AB  - Recent studies indicate that the normal intestinal flora, an exaggerated reaction
      of the intestinal immune system and a decreased epithelial barrier function of
      the gut play an important role in the pathogenesis of Crohn's disease and
      ulcerative colitis. The medical therapy of inflammatory bowel disease aims to
      correct these alterations. Aminosalicylates, corticosteroids, immunosuppressants
      and antibiotics are the four main groups of substances which are currently used
      for the therapy of inflammatory bowel diseases. Slow release formulation allow
      specific targeting of 5-aminosalicylic acid to the inflamed sections of the gut;
      with budesonid a corticosteroid therapy with minimal systemic side effects is
      possible. Future therapeutic options include specific immuno-modulatory therapy
      with cytokines or cytokine antibodies. Maintenance therapy may, conceivably, be
      performed with probiotics or antioxidants. Therefore, despite continued
      uncertainty about the cause of inflammatory bowel diseases, recent advances
      nourish the hope for further improvement of the control of disease activity and a
      better quality of life for patients with inflammatory bowel diseases.

PMID- 9530773
TI  - [Surgical treatment of inflammatory bowel diseases].
AB  - PURPOSE: To summarize current knowledge on surgical therapy in patients with
      inflammatory bowel disease (Crohn's disease, ulcerative colitis and
      diverticulitis). MATERIAL AND METHODS: To discuss surgical indications and
      strategies, we reviewed major peer review publications of the last 10 years, and
      we also analysed data from patients with Crohn's disease who were treated in our
      institution between 1978 and 1994. RESULTS: With Crohn's disease (305 patients),
      emergency surgery should be avoided as much as possible, since morbidity (50% vs
      8.8%) and mortality (11% vs 0.6%) rise significantly in comparison to elective
      procedures. With ulcerative colitis, operative therapy is indicated in patients
      with secondary malignoma, and urgent surgery is requested in cases with
      associated perforation, toxic megacolon or massive bleeding. With diverticulitis,
      the first episode should be managed conservatively. Surgery is indicated in
      patients with recurrent episodes or with secondary complications. DISCUSSION: For
      treating patients with Crohn's disease or with diverticulitis, an indication for
      surgery should not be delayed and should be made before complications develop to
      avoid high risk emergency surgery. Elective surgery in patients with ulcerative
      colitis usually consists in proctocolectomy. Individual findings and aspects will
      determine the decision whether to construct an ileoanal pouch or whether
      ileostoma is more appropriate.

PMID- 9530774
TI  - [Radiologic evaluation of Crohn disease].
AB  - PURPOSE: This paper discusses the role of different imaging modalities in the
      diagnostic work-up of Crohn's disease (CD). METHODS: We present a concept, which
      emphasizes different diagnostic aspects with regard to primary diagnosis, follow
      up and assessment of complications of CD. The most effective imaging approach to
      various diagnostic problems of CD is discussed in detail. DISCUSSION: With regard
      to the primary diagnosis barium studies should contribute to differentiate
      between CD and ulcerative colitis. Beyond that, these studies should evaluate
      location and extent of disease. During the follow-up bowel sonography provides
      staging of disease and enables the detection of complications at an early stage.
      CT is a valuable tool in the preoperative assessment of complications, such as
      fistulae and abscesses.

PMID- 9530775
TI  - [MRI of the abdomen combined with enteroclysis in Crohn disease using oral and
      intravenous Gd-DTPA].
AB  - In spite of the improved MR-diagnosis of the abdomen, MRI is not used as a
      routine method for the diagnosis of inflammatory small bowel disease. The aim of
      this study was--after optimazation of the bowel opacification--the correlation of
      the findings obtained with enteroclysis and MRI in patients with known Crohns'
      disease. 60 patients between 17 and 72 years of age were investigated. First, an
      enteroclysis was performed in typical manner. The applicated methylcellulosis was
      blended with positive oral MR contrast media (Magnevist oral, Schering). After
      enteroclysis, MRI of the abdomen was performed using T1- and T2-weighted
      breathhold sequences (Flash 2D pre- and postcontrast and TSE) in axial and
      coronal planes. The length of the affected bowel and the stenosis seen with
      enteroclysis correlated well with the visible thickening of the small bowel wall
      and the stenosis seen in MRI. Using MRI, additional findings could be obtained in
      28 patients, such as fistulas, abscesses or a hydronephrosis, or a better
      assessment of the stenosis was possible with MRI, because of the avoidance of
      overshadowing of the affected bowel loop with MRI. A brilliant MR-tomographic
      imaging of the small bowel is possible under the condition, that the small bowel
      contrast is optimal. The main prerequisite is a large filling volume of the small
      bowel to reach a homogeneous contrast and a good distension of the small bowel
      lumen.

PMID- 9530777
TI  - [Mesenteric lymphadenopathy in Yersinia enterocolitica infection].
AB  - We report a case of previously undiagnosed Yersinia enterocolitica infection in a
      46-year old woman. She consulted her physician because of continual weight loss
      and physical lassitude. A leucocytosis was found. Sonography revealed an
      excessive enlargement of abdominal lymph nodes. A malignant lymphoma was
      suspected and the patient underwent a staging by CT. There the disease was
      limited on mesenteric and retroperitoneal lymph nodes. Bone marrow biopsy and CT
      guided lymph node biopsy did not confirm a systemic lymphatic disease. The
      patient did not undergo a special therapy. After six months, CT showed a clear
      regression of enlarged lymph nodes. Finally, a previous Yersinia enterocolitica
      infection of immunotype 03 could be proved serologically. At this time, the
      patient had no complaints. Diagnostic and differential diagnosis of benign
      abdominal lymph node enlargement are discussed based on literature.

PMID- 9530776
TI  - [MRI of the small intestine with rapid MRI sequences in Crohn disease after
      enteroclysis with oral iron particles].
AB  - PURPOSE: To evaluate the efficacy of breathhold MRI following enteroclysis with
      addition of oral magnetic particles to study the extension, detection of stenoses
      and extraluminal manifestations in Crohn's disease. MATERIAL AND METHODS: 18
      patients with Crohn's disease and potential of surgical intervention were studied
      with enteroclysis with addition of oral magnetic particles. T1-/T2-weighted
      breathhold MRI w/o spectral fat suppression w/o i.v. Gd-DTPA was applied.
      RESULTS: Typical findings were marked bowel wall thickening with strong contrast
      enhancement. 95.8% of affected small bowel segments and 94.7% of stenoses were
      correctly detected by MRI. All four fistulas were detected and important
      extraluminal findings were seen in 6/18 patients. Additionally, one ileoileal and
      two ileosigmoidal adhesions, two extraluminal abscesses and affection of the
      right ureter were delineated. CONCLUSION: MRI in Crohn's disease offers the
      potential to avoid radiation exposure in this relatively young patient group.
      Important additional findings relevant to indication of surgery are seen in
      approximately one third of cases. The replacement of transduodenal intubation by
      oral contrast application remains to be further studied.

PMID- 9530778
TI  - [Inflammatory bowel diseases. Colon contrast enema and CT].
AB  - Among the many inflammatory diseases of the colon, Crohn's disease and ulcerative
      colitis occur most frequently. For primary evaluation, endoscopy has widely
      replaced the barium enema (BE) as diagnostic method. BE, however can provide
      important additional informations in the differential diagnosis of chronic
      inflammatory colonic diseases. Purpose of this article is the demonstration of
      typical, but also of atypical radiological changes in different stages of Crohn's
      disease and ulcerative colitis, as well as calling attention to the importance of
      CT. A BE demands a refined examination technique using double contrast. All CT
      examinations have to be scrutinized for changes of the bowel and mesentery. A
      dedicated spiral-CT examination might be indicated in a known disease in order to
      obtain special informations. The advantage of a BE over endoscopy is a clear and
      reproducible demonstration of the patterns of distribution and character of the
      disease as well as the detection of fistulae. The classification into one or the
      other disease entity can be better accomplished. CT is superior in detecting
      bowel wall thickening, extraintestinal disease and complications. In diagnostic
      imaging of chronic inflammatory bowel diseases, endoscopy and radiologic
      techniques are used complementarily.

PMID- 9530779
TI  - [Angiogenesis of cervix carcinoma. Contrast enhanced dynamic MRI, histologic
      quantification of capillary density and lymphatic system infiltration].
AB  - PURPOSE: It was the aim of this project to examine (i) the relationships between
      contrast-enhanced dynamic MR imaging derived characteristics and histologic
      microvessel density counts--a recognized surrogate of tumor angiogenesis--from
      tumors in patients with primary or recurrent cancer of the uterine cervix, and
      (ii) to correlate these parameters with lymphatic involvement (i.e. lymphatic
      channels) to assess tumor biological aggressiveness in terms of lymphatic spread.
      MATERIAL AND METHODS: Pharmacokinetic MR imaging parameters (amplitude A,
      exchange rate constant k21) were derived from contrast-enhanced dynamic MR
      imaging in thirty-three patients with biopsy proven cancer of the uterine cervix.
      The pharmacokinetic MR imaging characteristics were correlated to histologic
      capillary density counts obtained from whole mount specimen. In addition, these
      data were correlated to the angiogenic activity as a marker for lymphatic system
      involvement. RESULTS: Pharmacokinetic MR imaging derived parameters (A, k21)
      showed a weak but significant (p < 0.05) correlation with microvessel density
      counts. Lymphatic involvement was more comprehensively assessed by the
      pharmacokinetic parameter k21 compared with histologic microvessel density,
      resulting in a significantly (p < 0.05) higher overall accuracy (85% vs. 64%),
      sensitivity (83% vs. 54%), and comparable specificity (89% vs. 89%),
      respectively. CONCLUSION: Our first results show that the signal-time curves
      measured by contrast-enhanced MR imaging are only in part influenced by
      microvessel density. In addition, MR imaging derived characteristics may assess
      tumor biological aggressiveness in terms of lymphatic spread (i.e. lymphatic
      channels) more comprehensively than histologic microvessel density in patients
      with primary or recurrent cancer of the uterine cervix.

PMID- 9530780
TI  - [A 1 1/2-year-old child with "gastrointestinal symptoms". Tuberculous
      meningitis].

PMID- 9530781
TI  - In vivo Bcl-2 oncogene neuronal expression in the rat spinal cord.
AB  - STUDY DESIGN: An acute mechanical rat spinal cord injury model was used to
      investigate in vivo Bcl-2 oncogene overexpression in neuronal tissue. OBJECTIVES:
      To introduce the Bcl-2 oncogene in vivo by a recombinant adenovirus vector into
      rat spinal cord tissue, and to investigate any potential protective effect on
      neural tissue in the zone of injury in a rat spinal cord model. SUMMARY OF
      BACKGROUND DATA: The Bcl-2 oncogene inhibits apoptotic and necrotic neural cell
      death in vitro by regulating an antioxidant pathway at sites of free radical
      generation. Thus, overexpression of the Bcl-2 oncogene may have a role in
      limiting the secondary injury cascade of spinal cord injury through its
      regulation of antioxidants. METHODS: After confirmation of Bcl-2 gene expression
      in vitro and in vivo in the rat spinal cord, a weight-drop spinal cord injury
      model was performed on seven rats with prior Bcl-2 inoculation, and on seven rats
      with prior B-gal inoculation (controls). RESULTS: In vivo Bcl-2 expression was
      documented by immunostaining. After spinal cord harvest, quantification of
      percentage preserved tissue at the spinal cord injury site suggested that Bcl-2
      overexpression confers neuroprotection. CONCLUSIONS: In vivo Bcl-2 oncogene
      overexpression was successfully induced in neuronal tissue. After Bcl-2 oncogene
      expression in the rat spinal cord, the zone of microscopic injury was diminished.
      Further investigation of the Bcl-2 oncogene for potentially enhancing neuronal
      survival after spinal cord injury appears indicated.

PMID- 9530782
TI  - Inflammatory cells in full-thickness anulus injury in pigs. An experimental disc
      herniation animal model.
AB  - STUDY DESIGN: Inflammatory cells were studied by indirect immunocytochemistry in
      experimental full-thickness anulus fibrosus lesions in pigs. OBJECTIVES: First,
      to determine the occurrence, by immunocytochemistry, of T lymphocytes and
      macrophages in experimentally produced, anterolateral full-thickness disc lesions
      in pigs, and second, to compare the presence of inflammatory cells in 1) the
      injury area, 2) the adjacent noninjured part of the disc, and 3) control discs.
      SUMMARY OF BACKGROUND DATA: Previous studies on disc herniation material obtained
      from human disc surgeries have demonstrated inflammatory cells in a subgroup of
      herniations. Macrophages were most prevalent, being more numerous than
      lymphocytes. Macrophages have furthermore been suggested to be important in the
      resorption process of extruded disc tissue. No similar studies on an animal model
      of disc herniation, however, have so far been presented. METHODS: A full
      thickness anular incision, 10 mm long, was made with a scalpel in the L3-L4 or L4
      L5 intervertebral discs of 12 adult pigs. The incision was made in the
      anterolateral part of the disc. Nucleus material was observed outside the injury
      site when tissue samples were taken, suggesting a disc herniation. Tissue then
      was analyzed from the area of injury, from the area adjacent to the injury, and
      from separate control discs from three additional pigs of the same age. Thin
      frozen sections were studied by indirect immunocytochemistry (alkaline
      phosphatase anti-alkaline phosphatase method) using monoclonal anti-human
      antibodies applicable to porcine tissues, T lymphocytes (CD3), and macrophages
      (CD68). Cells were graded as: -, absent; (+), only a few scattered cells; and +,
      abundant cells. Disc tissue samples were taken 1 month (three discs), 2 months
      (four discs), and 3 months (five discs) after the operation. RESULTS: Macrophages
      were present more commonly than T cells, and were abundant in seven of 12 discs
      (58%), with T cells abundant in four of 12 discs (33%). Only a few macrophages
      were present in the injured tissue from one additional disc, and scattered T
      cells were seen in four additional discs. Abundant macrophages were also observed
      in one of two discs in the adjacent noninjured area, whereas only a few T
      lymphocytes at the most were present in such noninjured disc tissue. In four
      (33%) and three (25%) injured discs, respectively, no macrophages or T
      lymphocytes could be found. No inflammatory cells were observed in three of 12
      discs (25%). The three control discs showed no inflammatory cells. CONCLUSIONS:
      Inflammatory cells, predominantly macrophages, were present in a subsample of
      experimental discs with full-thickness anulus defects, as has previously been
      observed for human disc herniations. In this animal model, macrophages may have
      spread to adjacent noninjured parts of the disc. The induced herniation in this
      animal model is, however, anterolateral and may not fully correspond to clinical
      disc herniations, most of which are posterolateral. However, the results from
      this model support a role for inflammation in disc herniation.

PMID- 9530783
TI  - A biomechanical comparison of open and thoracoscopic anterior spinal release in a
      goat model.
AB  - STUDY DESIGN: A biomechanical assessment of anterior release and discectomy in
      the thoracic spine was performed on an animal model using thoracoscopic and open
      thoracotomy techniques. OBJECTIVES: To compare the relative efficacy of these two
      techniques of release in achieving increased spinal mobility. BACKGROUND DATA:
      The clinical use of video-assisted thoracoscopy in the correction of spinal
      deformity is increasing. The effectiveness of thoracoscopic anterior spinal
      release with discectomy has not been evaluated biomechanically. METHODS: Anterior
      release with discectomy was performed on six midthoracic motion segments in five
      mature goats. The thoracoscopic technique was used for three levels on one side,
      and an open thoracotomy was used for the alternating three levels of the
      contralateral side. The duration of surgery for disc excision and the amount of
      blood loss for each technique were recorded. The intact cranial and caudal motion
      segments served as controls. The motion segments were individually subjected to
      nondestructive biomechanical testing. Torsional, sagittal, and coronal bending
      torques were applied, and the resulting angular displacement was measured.
      RESULTS: The duration of surgery to remove a disc thoracoscopically decreased as
      experience was gained by the surgeon. The amount of intraoperative blood loss was
      comparable using the two methods. There was significantly increased flexibility
      in the released segments with both techniques, compared with the flexibility in
      the intact levels for all three loading directions. There was no difference in
      the motion obtained after release between the two techniques. CONCLUSION: Open
      and thoracoscopic anterior release and discectomy have been demonstrated, through
      biomechanical in vitro testing, to increase the flexibility of the spine to a
      similar extent.

PMID- 9530784
TI  - Influence of muscle forces on loads in internal spinal fixation devices.
AB  - STUDY DESIGN: The loads acting on an internal spinal fixation device were
      measured in vivo. OBJECTIVES: To determine the influence of muscle forces on
      implant loads. SUMMARY OF BACKGROUND DATA: Only limited information exists
      regarding the loads acting on spinal implants in vivo. Though the muscles greatly
      influence spinal load, they have been neglected in most studies. METHODS:
      Telemeterized internal spinal fixation devices were used to study the influence
      of muscle forces on the implant loads in three patients before and after anterior
      interbody fusion. RESULTS: Contracting abdominal or back muscles in a lying
      position was found to significantly increase implant loads. Hanging by the hands
      from wall bars as well as balancing with the hands on parallel bars reduced the
      implant loads compared with standing; however, hanging by the feet with the head
      upside down did not reduce implant loads compared with lying in a supine
      position. When lying on an operating table with only the foot end lowered so that
      the hips were bent, the patient had different load measurements in the conscious
      and anesthetized state before anterior interbody fusion. The anesthetized patient
      evidenced predominately extension moments in both fixators, whereas flexion
      moments were observed in the right fixator of the conscious patient. After
      anterior interbody fusion had occurred, the differences in implant loads
      resulting from anesthesia were small. CONCLUSIONS: The muscles greatly influence
      implant loads. They prevent an axial tensile load on the spine when part of the
      body weight is pulling, e.g., when the patient is hanging by his hands or feet.
      The implant loads may be strongly altered when the patient is under anesthesia.

PMID- 9530785
TI  - Stability potential of spinal instrumentations in tumor vertebral body
      replacement surgery.
AB  - STUDY DESIGN: The multidirectional stability potential of anterior, posterior,
      and combined instrumentations applied at L1-L3 was studied after L2 corpectomy
      and replacement with a carbon-fiber implant. OBJECTIVES: To evaluate the
      biomechanical characteristics of short-segment anterior, posterior, and combined
      instrumentations in lumbar spine tumor vertebral body replacement surgery.
      SUMMARY OF BACKGROUND DATA: The biomechanical properties of many different spinal
      instrumentations have been studied in various spinal injury models. Only a few
      studies, however, investigate the stabilization methods in spinal tumor vertebral
      body replacement surgery. METHODS: Eight fresh frozen human cadaveric
      thoracolumbar spine specimens (T12-L4) were prepared for biomechanical testing.
      Pure moments (2.5 Nm, 5 Nm, and 7.5 Nm) of flexion-extension, left-right axial
      torsion, and left-right lateral bending were applied to the top vertebra in a
      flexibility machine, and the motions of the L1 vertebra with respect to L3 were
      recorded with an optoelectronic motion measurement system after reconditioning.
      The L2 vertebral body was resected and replaced by a carbon-fiber cage. Different
      fixation methods were applied to the L1 and L3 vertebrae. One anterior, two
      posterior, and two combined instrumentations were tested. Load-displacement
      curves were recorded and neutral zone and range of motion parameters were
      determined. RESULTS: The anterior instrumentation provided less potential
      stability than the posterior and combined instrumentations in all motion
      directions. The anterior instrumentation, after vertebral body replacement,
      showed greater motion than the intact spine, especially in axial torsion (range
      of motion, 10.3 degrees vs 5.5 degrees; neutral zone, 2.9 degrees vs. 0.7
      degrees; P < 0.05). Posterior instrumentation provided greater rigidity than the
      anterior instrumentation, especially in flexion-extension (range of motion, 2.1
      degrees vs. 12.6 degrees; neutral zone, 0.6 degrees vs. 6.1 degrees; P < 0.05).
      The combined instrumentation provided superior rigidity in all directions
      compared with all other instrumentations. CONCLUSIONS: Posterior and combined
      instrumentations provided greater rigidity than anterior instrumentation.
      Anterior instrumentation should not be used alone in vertebral body replacement.

PMID- 9530786
TI  - A comparison of manual versus computer-assisted radiographic measurement.
      Intraobserver measurement variability for Cobb angles.
AB  - STUDY DESIGN: A comparison between computer-assisted measurement using digitized
      radiographs, which has the potential to reduce error, and manual measurement
      using standard radiographs. OBJECTIVE: To assess measurement variability for the
      Cobb method on digital radiographs and compare it with that of manual
      measurements on standard radiographs. BACKGROUND DATA: Studies of the Cobb method
      have demonstrated multiple sources of error leading to significant intraobserver
      measurement variability. Estimates for the 95% confidence interval for
      intraobserver variability range from 2.8 degrees to 10 degrees. METHODS: Twenty
      four scoliosis radiographs were measured by six examiners. Two measurement sets
      were done manually ("manual set"), and two measurement sets were done on
      digitized images using a computer mouse ("computer set"). RESULTS: For the manual
      set, the 95% confidence interval for intraobserver variability was 3.3 degrees
      (range, 2.5-4.5 degrees). For the computer set, the value was 2.6 degrees (range,
      2.3-3.3 degrees). This difference in 95% confidence intervals between the manual
      and computer sets was statistically significant (P < 0.001). CONCLUSIONS: The
      results of this study demonstrate that intraobserver variability for manual and
      computer Cobb angle measurements yield a 95% confidence interval of approximately
      3 degrees, with the computer having a slightly lower variability. The computer
      technique removes sources of intrinsic error, e.g., the variability introduced by
      using different manual protractors, the inaccuracy of standard protractors, and
      the use of wide-diameter radiographic markers. Identical digital images can be
      shared electronically between centers, without having to duplicate and mail
      films. Multicenter studies in which different examiners will be measuring Cobb
      angles may consider using the computer as a measuring device to reduce intrinsic
      measurement errors.

PMID- 9530787
TI  - Biomechanical aspects of the subarachnoid space and cervical cord in healthy
      individuals examined with kinematic magnetic resonance imaging.
AB  - STUDY DESIGN: In vivo flexion-extension magnetic resonance imaging studies of the
      cervical spine were performed inside a positioning device. OBJECTIVE: To
      determine the functional changes of the cervical cord and the subarachnoid space
      that occur during flexion and extension of the cervical spine in healthy
      individuals. SUMMARY OF BACKGROUND DATA: As an addition to static magnetic
      resonance imaging examinations, kinematic magnetic resonance imaging studies of
      the cervical spine were performed to obtain detailed information about functional
      aspects of the cervical cord and the subarachnoid space. The results were
      compared with published data of functional flexion-extension myelograms of the
      cervical spine. METHODS: The cervical spines of 40 healthy individuals were
      examined in a whole-body magnetic resonance scanner from 50 degrees of flexion to
      30 degrees of extension, using a positioning device. At nine different angle
      positions, sagittal T1-weighted spin-echo sequences were obtained. The images
      were analyzed with respect to the segmental motion, the diameter of the
      subarachnoid space, and the diameter of the cervical cord. RESULTS: The segmental
      motion between flexion and extension was 11 degrees at C2-C3, 12 degrees at C3
      C4, 15 degrees at C4-C5, 19 degrees at C5-C6, and 20 degrees at C6-C7. At
      flexion, a narrowing of the ventral subarachnoid space of up to 43% and a
      widening of the dorsal subarachnoid space of up to 89% (compared with the neutral
      position, 0 degrees) were observed. At extension, an increase in the diameter of
      the ventral subarachnoid space of up to 9% was observed, whereas the dorsal
      subarachnoid space was reduced to 17%. At flexion, there was a reduction in the
      sagittal diameter of the cervical cord of up to 14%, and, at extension, there was
      an increase of up to 15%, compared with the neutral position (0 degrees; these
      values varied depending on the cervical segment. Statistically significant
      differences (P < 0.05) were found between flexion and extension in the diameter
      of the ventral and dorsal subarachnoid space and in the diameter of the cervical
      cord. CONCLUSIONS: Compared with the results of previous studies using functional
      cervical myelograms, kinematic magnetic resonance imaging provides additional
      noninvasive data concerning the physiologic changes of the cervical subarachnoid
      space and the cervical cord during flexion and extension in healthy individuals.

PMID- 9530788
TI  - Evaluation of clinician and machine performance in the assessment of low back
      pain.
AB  - STUDY DESIGN: A prospective blind study to test and compare the performance of
      clinicians (evaluators) with that of an automated machine (the Spinoscope) in
      conducting an examination on randomly designated simulators/dissimulators and
      honest subjects to assess acute benign low back pain. OBJECTIVES: To test the
      impact of reported pain and history on the clinical examination and to compare
      the ability of clinicians and the machine to recognize normal findings in a
      controlled group of subjects with and without benign low back pain. BACKGROUND:
      The literature raises serious questions regarding the efficacy of the clinical
      examination for patients with low back pain. METHODS: A "gold standard" (clinical
      examination by experts in low back pain) was established against which the
      clinical examination by the evaluators and the machine assessment (incorporating
      weight-lifting ability) of honest subjects and simulators/dissimulators were
      compared using the receiver operating characteristic technique. The selection of
      subjects was performed according to strict inclusion and exclusion criteria.
      RESULTS: The evaluators were more accurate with the honest subjects, the machine
      more accurate with the simulators/dissimulators, and, for the entire population
      tested, the they were equivalent in accuracy (71% vs. 72% concordance). Results
      from the machine's expert system and from clinician readers of the machine data
      compared favorably. The machine's concordance with the gold standard increased
      with increasing loads lifted by the subject. CONCLUSION: By relying primarily on
      the subject's self-presentation, often to the exclusion of objective findings,
      the clinician may err in evaluating low back function when the patient does not
      report his or her true condition. The additional functional analysis provided by
      the machine offers the clinician objective, pertinent information to complement
      the findings from the clinical examination.

PMID- 9530789
TI  - The influence of muscle fiber size and type distribution on electromyographic
      measures of back muscle fatigability.
AB  - STUDY DESIGN: This was a cross-sectional study carried out on a group of 31
      healthy, consenting volunteers with no history of low back pain (17 men, 14
      women). OBJECTIVES: To evaluate the relationship between electromyographic
      measures of erector spinae fatigability and the muscle's fiber type
      characteristics. SUMMARY OF BACKGROUND DATA: Using electromyographic techniques,
      a pronounced fatigability of the muscles of patients with low back pain has been
      identified. It has been postulated that this is the result of an unfavorable back
      muscle fiber type distribution, although an association between electromyographic
      measures of fatigue and the muscle's fiber type characteristics has never been
      established. METHODS: Two tests of back extensor fatigability were performed (on
      separate days), each to the limit of endurance: 1) maintenance of 60% total
      maximum voluntary contraction of the back extensors, and 2) performance of the
      Biering-Sorensen test. Pairs of surface electrodes were attached to the skin
      overlying the belly of the erector spinae, bilaterally, at T10 and L3. The median
      frequency was computed from the electromyographic power spectrum, and
      fatigability was given by the slope of the linear regression of median frequency
      on time (MFgrad; %.s-1). One week later, two percutaneous erector spinae muscle
      biopsy samples were obtained from the same sites described for electromyography
      (left side only). Samples were prepared for histochemistry for the identification
      of muscle fiber types. Fiber sizes (cross-sectional areas) were quantified using
      computerized image analysis. RESULTS: The mean fiber size at each erector spinae
      region showed a significant correlation with maximum back extensor strength. In
      the thoracic region, the relative area of the muscle occupied by Type I fibers
      (which accounts for the relative size and distribution of the fiber types) showed
      a significant relationship with MFgrad recorded during each fatigue test. A
      similar relationship was observed for the lumbar region, but for the Biering
      Sorensen test only. CONCLUSIONS: The electromyographic changes recorded in back
      muscles during fatigue appear to be related to the underlying muscle fiber type
      area distribution. This confirms the usefulness of electromyography in reflecting
      such muscle characteristics in a noninvasive manner, when monitoring changes in
      function consequent to the development of, or rehabilitation from, low back pain.

PMID- 9530790
TI  - Imaging assessment of sacroiliac screw placement relative to the neuroforamen.
AB  - STUDY DESIGN: Twenty-four cannulated sacroiliac screws were placed bilaterally
      into 12 cadaveric pelvi (12 titanium screws and 12 stainless-steel screws) and
      were imaged using conventional and multiplanar reconstructed computed tomography.
      OBJECTIVES: To determine whether sacroiliac screw position assessment relative to
      the neuroforamen is enhanced by: 1) computed tomography using multiplanar
      reconstructions and 2) the use of titanium screws rather than stainless-steel
      screws. SUMMARY OF BACKGROUND DATA: To the authors' knowledge, there have been no
      prior studies demonstrating the accuracy of multiplanar computed tomography
      compared with that of conventional (axial) tomography in determining the position
      of sacroiliac screws relative to the neuroforamen. Although titanium screws have
      been shown to have less scatter than stainless-steel screws, the effect of alloy
      composition on the radiographic accuracy of interpreting the screw position
      relative to the sacral neuroforamen is unknown. METHODS: Screws were deliberately
      placed into: position A, in which the screw did not violate the neuroforamen;
      position B, in which the threads of the screw came within 3 mm of the
      neuroforamen; and position C, in which the screw clearly was nearly centered in
      the neuroforamen. The degrees of accuracy in assessing screw position relative to
      the neuroforamen using conventional (axial) images and using multiplanar
      reconstructed images were compared. RESULTS: The axial images were accurate in
      determining screw position relative to the neuroforamen in 50% of cases in which
      titanium screws were used and in 42% of cases in which stainless-steel screws
      were used. The corresponding values for multiplanar reconstructions were 92% for
      cases in which titanium screws were used and 67% for cases in which stainless
      steel screws were used. The accuracy of multiplanar reconstructions was
      statistically better than that of axial images (P < 0.05). Metallic scatter was
      increased in stainless-steel screws. CONCLUSIONS: The results of this study
      suggest that the use of computed tomography with multiplanar reconstruction
      improves accuracy in determining sacroiliac screw position relative to the
      neuroforamen. The assessment of screw position may be facilitated using titanium
      screws.

PMID- 9530791
TI  - Regional assessment of joint position sense in the spine.
AB  - STUDY DESIGN: A test-retest design was used to assess the reproducibility of
      position sense measurements of the spine recorded at T1, T7, L1, and S2.
      OBJECTIVES: To measure position sense at four spinal levels in healthy volunteers
      and to determine if this varies on a day-to-day basis. The overall purpose is to
      provide baseline data for studying position sense of the spine in patients with
      spinal lesions. SUMMARY OF BACKGROUND DATA: Position sense, which is one
      component of proprioception, is assessed by the ability to reposition the body
      after displacement. In peripheral joints, position sense is accurate to within a
      few degrees. Studies on the spine suggest similar accuracy, but most have used
      indirect methods of measurement that often incorporate unusual extraneous cues.
      METHODS: Spinal position sense was assessed in 20 healthy volunteers using an
      electromagnetic movement sensor system, the 3-Space Fastrak (Polhemus,
      Colchester, VT), to measure absolute error in actively reproducing upright and
      flexed positions during movements in both coronal and sagittal planes. Three
      randomized measurements were taken for each position in one testing session, and
      measurements were repeated in all participants 2 weeks later. RESULTS: Same-day
      measurements indicate that spinal position sense is reproducible in upright
      postures to within a mean of 3.79 +/- 2.56 for movements in the sagittal plane
      and 2.26 +/- 1.59 degrees for movements in the coronal plane. Corresponding
      measurements for flexed postures are 5.27 degrees +/- 3.47 degrees and 3.70 +/-
      2.62 degrees, respectively. Intraclass correlation coefficients between repeated
      measurements are generally good in the sagittal plane but are affected by side
      dominance in the coronal plane. Also, repositioning errors tend to increase on
      ascending the spine. Repeat measurements taken 2 weeks later show similar values.
      CONCLUSIONS: 1) Healthy volunteers were able to reposition their spine with
      considerable accuracy as measured with the 3-Space Fastrak; 2) this ability does
      not change significantly on a day-to-day basis; and 3) the 3-Space Fastrak offers
      a noninvasive and accurate method for the measurement of spinal position sense.

PMID- 9530792
TI  - Socioeconomic outcomes of combined spine surgery and functional restoration in
      workers' compensation spinal disorders with matched controls.
AB  - STUDY DESIGN: A longitudinal cohort study (n = 448) comparing functionally
      restored discectomy (n = 123) and fusion (n = 101) workers' compensation patients
      to matched, unoperated control patients (n = 123 and n = 101, respectively).
      OBJECTIVES: To determine successful treatment outcomes uniquely important in a
      workers' compensation environment when spine surgery is combined with
      comprehensive tertiary rehabilitation, to optimize anatomic and social sequelae.
      SUMMARY OF BACKGROUND DATA: Multiple recent studies confirm suboptimal
      socioeconomic outcomes for spinal surgery for degenerative conditions in a
      workers' compensation venue. In other musculoskeletal regions, there is a clear
      relationship between the quality of postsurgical rehabilitation and the impact on
      disability, recurrent injury, and future health care use. It is hypothesized that
      poor surgical outcomes in compensation injuries may result from outmoded
      postoperative methods, rather than failures of patient selection or surgical
      technique. No previous combination of surgery plus rehabilitation has been
      carefully evaluated with disabled workers undergoing spine surgery. Functional
      restoration is an individualized medically directed, interdisciplinary program
      using quantitatively directed exercise progression, psychotherapeutic
      interventions, and monitoring of specific socioeconomic outcomes for chronically
      disabled workers. METHODS: This study prospectively evaluated a cohort of
      consecutive functional restoration program graduates (n = 1202). Two surgical
      groups, discectomy (n = 123) and fusion (n = 101) were matched to two groups of
      unoperated control patients, control/discectomy and control/fusion, selected from
      the same cohort of patients with chronic spinal disorders based on age, gender,
      race, length of disability, and workers' compensation jurisdiction. A structured
      clinical interview was administered 12 months after program completion, with a
      contact rate of 95% to 98%. RESULTS: Socioeconomic outcomes for work return,
      health care use, and recurrent lost-time injury were assessed. All groups
      demonstrated a return-to-work incidence of more than 85%, but work retention at 1
      year was higher for the fusion group than for the discectomy or control/fusion
      groups. Health care use was significantly higher for the discectomy group than
      the control/discectomy or fusion groups for reoperation (8% vs. 4%/ 2%), as well
      as other factors. All groups showed comparable recurrent lost-time injury rates
      (2-3.3%), and made comparable improvements in prospectively collected physical
      and psychological measures. CONCLUSIONS: Discectomy patients had work, health
      care utilization, and recurrent injury outcomes comparable with those for
      unoperated control patients. Fusion patients had better outcomes of work
      retention, reoperation, and health care use compared with the unoperated control
      patients and even with discectomy patients, in spite of more cases of previous
      surgery and greater duration of disability. The discectomy and fusion cohorts of
      operated chronic spinal disorder compensation patients with subsequent functional
      restoration had the best documented outcomes found in the literature for this
      population. In spite of the common presumption that spine surgery patients fare
      poorly in a workers' compensation environment, these results demonstrate that
      such patients can show remarkably successful objective outcomes if accompanied by
      effective rehabilitation, documenting efficacy and clinical utility. A new
      clinical approach is required to evaluate prospectively the combination of
      surgery and rehabilitation in chronic pain/disability workers' compensation
      patients, in which the surgical role is to correct an anatomic lesion, but the
      socioeconomic outcomes either occur spontaneously or are effected through some
      form of rehabilitation.

PMID- 9530793
TI  - Medication use for low back pain in primary care.
AB  - STUDY DESIGN: A longitudinal observational study of primary care patients with
      low back pain. OBJECTIVES: 1) To describe medications prescribed for back pain,
      2) to identify patient characteristics associated with type of drug therapy, 3)
      to determine if the prescription of certain drugs is associated with better
      outcomes, and 4) to compare physician prescribing behavior with national
      guidelines. SUMMARY OF BACKGROUND DATA: Few previous studies have focused on
      medication prescribing patterns for back pain in primary care. METHODS: Two
      hundred nineteen patients aged 20-69 years who were making a first visit for an
      episode of back pain were studied. After the visit, patients completed
      questionnaires regarding sociodemographic characteristics, health status, back
      pain experience, and use of medications. Symptom severity and dysfunction were
      assessed by telephone 1 week after the visit. RESULTS: Sixty-nine percent of
      patients were prescribed nonsteroidal anti-inflammatory drugs, 35% muscle
      relaxants, 12% narcotics, and 4% acetaminophen. Twenty percent received no
      medications. Patients were more likely to receive medications if they had a
      desire for medication, pain below the knee, less than 3 weeks of pain before
      visit, more severe symptoms, or greater dysfunction. Patients with more severe
      symptoms were more likely to receive narcotics or muscle relaxants. Patients with
      greater dysfunction were also more likely to receive narcotics. Type of drug
      therapy predicted symptom severity but not dysfunction after 1 week. Controlling
      for other factors, those receiving medications had less severe symptoms after 1
      week than patients who received no medication. Patients receiving both muscle
      relaxants and nonsteroidal anti-inflammatory drugs had the best outcomes.
      Medication use for back pain in this health maintenance organization was
      generally concordant with national guidelines. CONCLUSIONS: Nonsteroidal anti
      inflammatory drugs, often augmented by muscle relaxants, are a standard medical
      treatment for back pain in primary care. In this observational study, patients
      prescribed medications, particularly muscle relaxants, reported less severe
      symptoms after 1 week than those receiving no medications. However, randomized
      trials are needed to determine which medication or combinations of medications
      are most effective.

PMID- 9530794
TI  - Spondylodiscitis after lumbar discectomy. Incidence and a proposal for
      prophylaxis.
AB  - STUDY DESIGN: An analysis of the incidence of spondylodiscitis after lumbar disc
      surgery in 1642 patients. In 508 patients no prophylactic antibiotics were given.
      In 1134 patients a collagenous sponge containing gentamicin was placed in the
      cleared disc space. OBJECTIVES: To report the incidence of postoperative
      spondylodiscitis in cases in which no antibiotic prophylaxis was used, and to
      define the value of a collagenous sponge containing gentamicin in preventing disc
      space infections. SUMMARY OF BACKGROUND DATA: Spondylodiscitis is considered to
      be a rare complication of lumbar disc surgery. The retrospective design of most
      studies and the rare use of magnetic resonance imaging for early radiologic
      diagnosis suggest that the reported incidence rates may be underestimates.
      Postoperative spondylodiscitis is the result of intraoperative contamination and,
      theoretically, could be prevented by treating these patients with prophylactic
      antibiotics. METHODS: In 1642 patients, 1712 discectomies were performed. In 508
      of these patients no prophylactic antibiotics were given; in 1134 of these
      patients a collagenous sponge containing gentamicin was placed in the cleared
      disc space. Clinical reexamination and, in cases of unsatisfactory results,
      laboratory and radiologic investigations were performed 4-8 weeks after surgery.
      RESULTS: In nineteen of the 508 patients who were not treated with antibiotic
      prophylaxis (3.7%) a postoperative spondylodiscitis developed, whereas none of
      the 1134 patients who received antibiotic prophylaxis became symptomatic (P <
      0.00001). CONCLUSION: In the current study, a 3.7% incidence of postoperative
      spondylodiscitis was found in the absence of prophylactic antibiotics. Gentamicin
      containing collagenous sponges placed in the cleared disc space were effective in
      preventing postoperative spondylodiscitis.

PMID- 9530795
TI  - Aneurysmal bone cyst of the spine. Management and outcome.
AB  - STUDY DESIGN: The clinical records, radiographs, histologic sections, and
      operative reports of 52 consecutive patients with an aneurysmal bone cyst of the
      spine were reviewed to evaluate diagnostic and therapeutic options and to
      correlate treatment and outcome. OBJECTIVES: To define the incidence, clinical
      presentation, diagnostic and therapeutic options, and prognosis of patients with
      aneurysmal bone cyst of the spine. SUMMARY OF BACKGROUND DATA: There are special
      considerations in the management of spinal lesions: relative inaccessibility of
      the lesions, associated intraoperative bleeding, necessity of removing the entire
      lesion to avoid the possibility of recurrence, proximity of the lesion to the
      spinal cord and nerve roots, and potential postoperative bony spinal instability.
      METHODS: Fifty-two consecutive patients with an aneurysmal bone cyst of the spine
      were treated from 1910 to 1993. Forty patients initially treated for a primary
      lesion had operative treatment (19 intralesional excision and bone grafting and
      21 intralesional excision); four also had adjuvant radiation therapy.
      Preoperative arterial embolization was performed in two. RESULTS: There was a
      recurrence rate of 10% within 10 years. All recurrences were noted less than 6
      months after surgery. Of 12 patients treated for a recurrent lesion, two had a
      subsequent recurrence (16.7%) within 9 years. At last follow-up examination, 50
      patients (96%) were free of the disease. One patient died of postradiation
      osteosarcoma, and one died of intraoperative bleeding. CONCLUSION: Current
      treatment recommendations involve preoperative selective arterial embolization,
      intralesional excision curettage, bone grafting, and fusion of the affected area
      if instability is present.

PMID- 9530796
TI  - Historical perspective. Ernest Amory Codman, 1869-1940. A pioneer of evidence
      based medicine: the end result idea.
AB  - Unappreciated during his career and largely uncelebrated today, Ernest A. Codman
      made profound contributions to medical practice and outcomes research. The origin
      of the present emphasis on evidence-based medicine began with Codman and his "end
      result" idea. Codman's ideas, courage, and persistence played a critical role in
      the transition from the 19th century artisan style of medical practice to the
      current scientific basis of medicine. This historical perspective is a tribute to
      Codman's contributions to medical science and highlights his remarkable career.

PMID- 9530797
TI  - Spine update lumbar interbody cages.
AB  - Interbody cage devices, used to assist interbody fusion, are rapidly gaining
      popularity in the surgical management of chronic low back pain. This update
      provides a structural classification of commonly used devices and assesses them
      against a set of clearly defined surgical goals, including ability to correct the
      existing mechanical deformation, ability to provide mechanical stability, ability
      to provide a suitable environment for arthrodesis, and ability to limit "built
      in" morbidity. In addition, the materials used in the devices are examined
      regarding their biomechanical, biologic, and radiographic characteristics.

PMID- 9530798
TI  - Results of a prospective cohort study of 443 patients who sought care for low
      back pain.

PMID- 9530800
TI  - A tribute to J. Calvin Giddings.

PMID- 9530799
TI  - Magnetic resonance imaging (MRI) scans.

PMID- 9530801
TI  - Exposure to captan in fruit growing.
AB  - This study characterized occupational exposure to pesticides in fruit growing in
      The Netherlands to assess determinants of exposure. Large-scale exposure surveys
      were carried out during application of pesticides and during reentry activities.
      Data on contamination inside the fruit growers' homes were obtained, and total
      potential exposure for the fruit grower and his family during the growing and
      harvesting season was estimated. Repeated measurements on the same subject were
      collected to study components of exposure variability. Relative contribution of
      the respiratory route and different skin sites to total exposure were assessed.
      Captan was used as a marker for exposure. Inhalable dust exposure was measured
      with a personal monitor and potential dermal exposure with skin pads and hand
      rinsing. Dislodgeable foliar residue was measured by taking leaf punches. For
      respiratory exposure and potential dermal exposure, differences were observed
      between several tasks. Workers were categorized according to tasks performed
      depending on the exposure measure(s) (e.g., hands, forehead, inhalable dust)
      considered relevant for a specific study purpose. In general, within-worker
      variability of all exposure measurements was larger than between-worker
      variability. Variability in dermal exposure on the same body location was small
      relative to variability between different body locations. Differences in total
      exposure, including exposure inside the home, between the fruit grower and the
      son were small. Exposure of the wife was two to three times lower than for the
      fruit grower and the son. As exposure per unit of time was in the same order of
      magnitude for different tasks, individual time spent on these tasks is crucial
      for estimating total potential exposure. Repeated measurements are necessary to
      estimate individual exposure accurately because of the large within-worker
      variability.

PMID- 9530802
TI  - Determinants of exposure to captan in fruit growing.
AB  - A series of studies investigated occupational exposure to pesticides among fruit
      growers in The Netherlands during spraying and reentry of orchards between 1990
      and 1992 to identify and quantify determinants of exposure. Determinants of
      exposure are discussed as a starting point for hazard identification and control.
      Captan was used as a marker for exposure. Cabin use of the tractor was the most
      prominent determinant of dermal exposure during spraying. For respiratory
      exposure, factors related to preparation of pesticides were most prominent. A
      long duration of exposure may reflect a different exposure situation compared
      with a short duration of exposure. As different determinants of exposure
      prevailed for each subgroup, consideration should be given to constructing
      exposure models for each group separately. Dislodgeable foliar residue (DFR) was
      the most prominent determinant of exposure for both respiratory and dermal
      exposure during reentry. However, no significant relation between DFR and dermal
      exposure of forehead and sternal area was found, perhaps because there was no
      direct contact with foliage here. Therefore, use of a transfer factor based on
      DFR to estimate total dermal exposure is only a crude estimate. The half-life of
      captan on crops varied from 10-17 days, so substantial exposure when entering the
      orchard is very likely, particularly when spraying frequency is high. The main
      starting points for reduction of exposure are use of a cabin, DFR, and individual
      time spent on different tasks. Determinants that are constant over time (cabin
      use) may have an especially great influence on grouping workers, according to
      long-term exposure in epidemiological studies. As determinants of exposure vary
      for the different exposure routes and body locations (for dermal exposure), the
      measure of interest for a specific study design will decide which determinants
      are most relevant.

PMID- 9530803
TI  - Aerosol penetration behavior of respirator valves.
AB  - Exhalation and inhalation valves from half-facepiece negative pressure
      respirators were evaluated for leakage during an 8-hour cyclic breathing test
      period using two work rates (415 and 622 kg-m/min) and two particle sizes (0.3
      and 0.8 micron). Three different models (manufacturers) of exhalation valves were
      tested, with two lots for each model. Exhalation valve leakage ranged from 0.0 to
      0.03%; no failure of exhalation valves occurred. No differences in lot or
      manufacturer were found. Differences in particle size did not lead to differences
      in penetration at the lower work rate; at the higher work rate 0.3-micron
      particles were less penetrating than 0.8-micron particles (0.03 versus 0.06%).
      When tested for air leakage at a pressure of 2.54 cm H2O, following the National
      Institute for Occupational Safety and Health certification method, exhalation
      valves exhibited no leakage either before or after the experiments. Inhalation
      valves averaged 20% leakage for all experiments; 0.3-micron particles were again
      less penetrating (13%) than 0.8-micron particles (27%). No inhalation valve
      failure occurred. No differences in lot (within manufacturer) were found; there
      were, however, significant differences in particle penetration among the three
      manufacturers' inhalation valves. Airflow leakage through the inhalation valves
      did not change during the experimental period, but differed among the three
      manufacturers. Measurements using airflow leakage and particle penetration
      produced the same ranking for the three manufacturers' inhalation valves.

PMID- 9530804
TI  - Indoor behavior and risk assessment following space spraying of d-tetramethrin
      and d-resmethrin.
AB  - To clarify the indoor behavior of insecticides in space spraying, an aerosol
      canister (containing a mixture of 0.45 g d-tetramethrin and 0.06 g d-resmethrin
      in a 300-mL product) was applied to a typical Japanese room under various
      conditions and temporal concentrations in air; floor, walls, and ceiling were
      monitored. Air concentrations were chiefly dependent on ventilation rates but not
      on air circulation by an air conditioner. During a periodic spraying, the
      airborne insecticides did not accumulate in the room, but the floor residues
      gradually increased with the number of sprayings. After cessation of spraying,
      however, dislodgeable residues on the floor decreased with time. The time
      dependent behavior of d-tetramethrin was simulated by a mathematical model
      (InPest) developed by the authors, and it was found that the estimated values
      agreed fully with actually measured values. The simulation model also clarified
      the amount of insecticide evaporated from the room material, the amount vented to
      the outdoors, and so on. Indoor exposure levels of d-tetramethrin and d
      resmethrin to the room's occupants were estimated with the monitored
      concentrations when a 10-sec spraying was done twice a day for 30 days. The
      margins of safety, which were obtained by dividing the no observed effect levels
      by the exposure levels, were over 100 for unclothed occupants, even in the room
      with the windows closed.

PMID- 9530806
TI  - An environmental chamber for investigating the evaporation of volatile chemicals.
AB  - An inexpensive test chamber has been constructed that provides an environment
      appropriate for testing the effects of temperature and chemical interactions on
      gaseous emissions from test solutions. Temperature, relative humidity, and
      ventilation rate can be controlled and a well-mixed atmosphere can be maintained.
      The system is relatively simple and relies on heated tap water or ice to adjust
      the temperature. Temperatures ranging from 9 to 21 degrees C have been
      maintained. At an average temperature of 15.1 degrees C, temperatures at any
      location within the chamber vary by no more than 0.5 degree C, and the
      temperature of the test solution within the chamber varies by no more than 0.1
      degree C. The temperatures within the chamber are stable enough to generate
      precise steady-state concentrations. The wind velocities within the chamber are
      reproducible from run to run. Consequently, the effect of velocity on the rate of
      evaporation of a test chemical is expected to be uniform from run to run. Steady
      state concentrations can be attained in less than 1 hour at an air exchange rate
      of about 5 per hour.

PMID- 9530805
TI  - Indoor behavior and risk assessment following residual spraying of d-phenothrin
      and d-tetramethrin.
AB  - To clarify the indoor behavior of insecticides in residual spraying equivalent to
      a crack and crevice treatment, an aerosol canister (containing a mixture of 0.9 g
      d-phenothrin and 1.1 g d-tetramethrin in a 300-mL product) was applied to a
      typical Japanese room under various conditions, and temporal concentrations in
      air and on the floor, walls, and ceiling were monitored. Air concentrations were
      chiefly dependent on ventilation rates but not on air circulation. During a
      periodic spraying, the airborne insecticides did not accumulate in the room, but
      the floor residues gradually increased with the number of sprayings. After
      cessation of spraying, however, dislodgeable residues on the floor decreased with
      time. The time-dependent behavior of d-phenothrin was simulated by a developed
      simulation model (InPest), which helped a more comprehensive understanding of the
      insecticide behavior. Indoor exposure levels of d-phenothrin and d-tetramethrin
      to room occupants were estimated with the monitored concentrations when a 2.5-min
      spraying was done four times over an 8-week period. The margins of safety, which
      were obtained by dividing the no observed effect levels by the exposure levels,
      were over 100 for unclothed occupants, even in a room with the windows closed.

PMID- 9530807
TI  - Occupational noise exposure of operators of heavy trucks.
AB  - Over 400 measurements were taken across Canada to assess the noise exposure of
      truck operators. The exposure of the driver was evaluated using both 3-dB (Leq)
      and 5-dB (L5dB) exchange rates. Driving with windows closed and radio not
      operating resulted in the lowest exposure. The drivers' Leq ranged from 78 to 89
      dBA, with a mean of 82.7 dBA; operating the radio increased the mean by 2.8 dB;
      driving with the driver's side window open increased the mean exposure by 1.3 dB;
      and driving with the window open and operating the radio resulted in an increase
      of 3.9 dB. Trucks with cabs mounted over the engine appear to be quieter than
      standard trucks by about 2.6 dB. Operations on four-lane highways are 1.6 dB
      noisier than on two-lane highways, most likely as a result of higher speeds on
      the former. Long haul (city-to-city) operations on hilly terrain appear to be
      quieter than on flat terrain by about 2.2 dB, again probably indicating the
      strong effect of speed. Regression analysis was used to obtain relationships
      between a number of variables such as Leq and L5dB, etc. These measurements
      indicate that the exposure of a driver is almost certain to exceed the current
      threshold limit value for noise (85 dBA for 8 hours with a 3-dB exchange rate)
      when driving with the radio on and the driver's side window open. Comparable
      numbers in terms of L5dB are also reported.

PMID- 9530808
TI  - Sulfated compounds from marine organisms.
AB  - More than 500 sulfated compounds have been isolated from marine organisms so far
      but most of them originate from two phyla only, Spongia and Echinodermata. The
      sulfated compounds are presented according to the phyla they have been identified
      from and to their chemical structures. Biological activities, when available, are
      also given. Macromolecules have also been included in this review but without
      structural details.

PMID- 9530810
TI  - Can phosphorylation and dephosphorylation of rod outer segment membranes affect
      phosphatidate phosphohydrolase and diacylglycerol lipase activities?
AB  - Phosphatidate phosphohydrolase (PAPase) and diacylglycerol lipase (DGL) enzymatic
      activities were found to be differently affected by preincubation of rod outer
      segments (ROS) under protein phosphorylation or dephosphorylation conditions in
      darkness or in light. Under protein kinase C (PKC) phosphorylation conditions,
      PAPase and DGL were inhibited in darkness and in light. The inhibitory effect on
      PAPase and DGL activities by PKC phosphorylation in the presence of light was
      more pronounced when the activities were compared with the activities in control
      membranes determined in the presence of EGTA. The addition of PKC activators such
      as phorbol-12,13-dibutyrate and dioctanoylglycerol (DOG) instead of DG produced
      the same pattern of changes in enzymatic activities. Pretreatment of ROS
      membranes with cAMP-dependent protein kinase (PKA) produced a significant
      increase in both enzymatic activities in the presence of light. No changes were
      observed when ROS proteins were phosphorylated by PKA in the dark.
      Dephosphorylation of ROS membranes with alkaline phosphatase resulted in a
      decrease in PAPase activity that was more marked under light than under dark
      conditions. DGL activity was not modified under dephosphorylation conditions.
      These findings suggest that the metabolization of phosphatidic acid in isolated
      ROS is differently affected by protein phosphorylation and dephosphorylation
      reactions.

PMID- 9530814
TI  - Effects of temperature and storage conditions on the electrophoretic, toxic and
      enzymatic stability of venom components.
AB  - Rattlesnake venoms are complex biological products containing potentially
      autolytic components, and they provide a useful tool for the study of long-term
      maintenance of enzymes in a competent state, both in vivo and in vitro. To
      evaluate the stability of venom components, 15 aliquots of freshly extracted
      venom (from Crotalus molossus molossus) were subjected to 15 different
      temperature and storage conditions for 1 week and then lyophilized; conditions
      varied from storage at -80 degrees C (optimal preservation of activities) to
      dilution (1:24) and storage at 37 degrees C (maximal degradation potential).
      Effects of different storage conditions were evaluated using SDS-PAGE,
      metalloprotease zymogram gels, a cricket LD50 assay and enzyme assays
      (metalloprotease, serine proteases, phosphodiesterase, L-amino acid oxidase and
      phospholipase A2). Venom samples were remarkably refractive to widely varying
      conditions; enzyme activities of some samples were variable, particularly L-amino
      acid oxidase, and one sample treatment showed higher toxicity, but
      electrophoretic results indicated very little effect on venom proteins. This
      study suggests that most venom activities should remain stable even if stored or
      collected under potentially adverse conditions, and freezing samples is not
      necessarily advantageous. Proteins in the crude venom are not as labile as has
      been previously thought, and endogenous mechanisms present in the venoms likely
      inhibit autolysis during long-term storage that occurs in vivo in the gland.

PMID- 9530812
TI  - Oxidation of fatty acids by kidney microsomes of musk shrew (Suncus murinus).
AB  - Substrate specificity and other properties of a fatty acid monooxygenase system
      in kidney microsomes of the Japanese house musk shrew (Suncus murinus) were
      examined. The suncus kidney microsomes catalyzed the hydroxylation of various
      saturated and unsaturated fatty acids to the omega- and (omega-1)-hydroxy
      derivatives. Laurate was most effectively hydroxylated among saturated and
      unsaturated fatty acids. The specific activity (53.79 +/- 5.59 [mean +/- SD, n =
      6] nmol/nmol cytochrome P450/min) of laurate in suncus kidney microsomes was very
      high compared with that in liver and kidney microsomes of other species. C18
      unsaturated fatty acids were converted to epoxides by a cytochrome P450-dependent
      fatty acid monooxygenase system in suncus kidney microsomes, in addition to omega
      and (omega-1)-hydroxylation products. The monooxygenase system metabolized
      arachidonic acid only to omega- and (omega-1)-hydroxylation products, not to
      epoxidation products.

PMID- 9530815
TI  - Primary structure of scombrine alpha: two different species with an identical
      protamine.
AB  - We have studied the protamine scombrine alpha from the mackerel Scomber scombrus.
      Scombrine alpha is found phosphorylated in spermatid nuclei, but not in nuclei of
      ripe sperm. It is a typical fish protamine, made up of two distinct molecular
      species, each of 34 amino acid residues. The primary structure of the main
      component of scombrine alpha is 100% identical to scombrine gamma, the
      nonmicroheterogeneous protamine from Scomber australasicus (11). The second
      component of scombrine alpha is a very minor molecular species that has an
      isoleucine instead of a valine in position 11. Nuclear sperm-specific basic
      proteins display an enormous interspecific variability and it is very surprising
      that two different species show identical protamines. In this work we suggest
      that evolutionary changes in primary structure of protamines are restricted by
      several constitutive factors, especially when protamines either lack or have a
      low degree of microheterogeneity.

PMID- 9530816
TI  - Influence of gender on selenoprotein W, glutathione peroxidase and selenium in
      tissues of rats.
AB  - After feeding a commercial rodent chow for 8 weeks, tissues from male and female
      rats were collected and examined for selenium content, glutathione peroxidase
      (GPX) activities and selenoprotein W (Se-W) levels. There were no differences (P
      > 0.05) between plasma selenium content, plasma GPX activity, whole blood
      selenium content, or whole blood GPX activity between male and female rats. There
      was also no gender effect on selenium concentration in muscle, brain, spleen, and
      skin, but selenium concentration in liver was higher (P < 0.05) in female than in
      male rats. Western blots indicated that the tissue distribution of Se-W was
      similar in male and female rats. Se-W protein level was high in testes of male
      rats but very low in ovaries of female rats. Muscle and skin from female rats had
      significantly higher (P < 0.05) Se-W levels than from male rats. Consistent with
      Se-W content, the Se-W mRNA levels from female skins were significantly higher (P
      < 0.05) than from male rats. The expression of Se-W was different in various
      tissues and gender influenced this regulation in some tissues.

PMID- 9530817
TI  - Identification of alternatively spliced Na(+)-Ca2+ exchanger isoforms expressed
      in the heart.
AB  - Alternatively spliced isoforms of Na(+)-Ca2+ exchanger were found from various
      tissues and species. RT-PCR amplification was performed on the basis of our
      cloned mouse cardiac Na(+)-Ca2+ exchanger and four alternatively spliced isoforms
      of Na(+)-Ca2+ exchanger were identified. Three (NCX1.3, NCX1.4, and NCX1.12) of
      them were first identified in the heart, and one isoform (NCX1.12) was a novel
      spliced variant. These four spliced variants were present in the embryonic and
      adult atria and ventricles. Different cell types of the heart expressed different
      spliced isoforms of Na(+)-Ca2+ exchanger. Southern blot analysis indicated that
      the Na(+)-Ca2+ exchanger gene existed as a single copy in the mouse genome. Thus,
      the Na(+)-Ca2+ exchanger isoforms expressed in mouse heart are consistent with
      being produced by alternative splicing and they may have different functions in
      various cell types in the mouse heart.

PMID- 9530818
TI  - Species variability of erythrocyte transport ATPases in mammals.
AB  - Na+, K(+)-ATPase, and Ca(2+)-ATPase in whole erythrocytes from five species of
      mammals (rat, mouse, guinea pig, golden hamster, rabbit) after cell treatment
      with Tween 20 (7.5 mg/ml) varied over a wide range: from 3.0 +/- 0.9 mumol
      Pi/hr/ml cells in rabbit to 27.3 +/- 4.9 mumol Pi/hr/ml cells in mouse for Na+,
      K(+)-ATPase and from 8.0 +/- 1.6 mumol Pi/hr/ml cells in hamster to 47.2 +/- 4.9
      mumol Pi/hr/ml cells in mouse for Ca(2+)-ATPase. Differences were less pronounced
      in red cell ghosts. Fatty acid and phospholipid compositions of erythrocyte
      membranes were similar for all species. Nevertheless, the activity of Ca(2+)
      ATPase in ghosts significantly correlated (r = -0.884) with the ratio of PC +
      SM/PE + PS in red cell membranes. Rabbit membranes had the lowest content of
      arachidonate. Rat hemolysate activated Na+, K(+)-ATPase in the ghosts from the
      animals of any species investigated, whereas the enzyme activation by the
      homohemolysate was characteristic only of the rat, mouse, and guinea pig ghosts.
      The data obtained suggest that there are differences in both activity and
      intracellular control of transport ATPase in erythrocytes of different mammals.

PMID- 9530819
TI  - The acute phase response of plasma proteins in the polyprotodont marsupial
      Monodelphis domestica.
AB  - In eutherians, patterns of plasma protein levels in blood change during the acute
      phase response to trauma and inflammation. Until now, such an acute phase
      response has not been characterised in a noneutherian species. Here we describe
      the acute phase response in a marsupial species, the South American polyprotodont
      marsupial Monodelphis domestica, after brain surgery or injection of
      lipopolysaccharide. Several days after brain surgery, transthyretin was not
      detected in plasma. For 48 hr following injection of lipopolysaccharide, the
      concentration of haptoglobin in plasma increased, that of transthyretin
      decreased, and the concentration of albumin in plasma did not change
      significantly. The American polyprotodont marsupials are probably more closely
      related to the common ancestor marsupial than the Australian marsupials are. It
      is most likely that the transthyretin gene was not expressed in the liver of this
      common ancestor. As the transthyretin gene is expressed in the liver of M.
      domestica, it seems that as soon as transthyretin is synthesised by the liver, it
      is under negative acute phase control.

PMID- 9530820
TI  - Characterization of exoskeletal proteins from the American lobster, Homarus
      americanus.
AB  - Proteins from the calcified exoskeleton of the lobster, Homarus americanus, were
      extracted and separated by two-dimensional gel-electrophoresis. Electroblotting
      the proteins onto polyvinylidene difluoride (PVDF) membranes followed by sequence
      determination gave 16 N-terminal amino-acid sequences and revealed that further
      eight proteins were N-terminally blocked. The relative molecular mass, M(r), was
      obtained for most of the electrophoretically separated proteins by means of
      matrix-assisted laser desorption mass spectrometry (MALDIMS) after electroelution
      from Coomassie-stained two-dimensional polyacrylamide gels. Eleven proteins were
      purified from extracts of the exoskeleton by low pressure ion exchange
      chromatography and reversed-phase high performance chromatography, and their
      sequences were determined by combined use of Edman degradation and mass
      spectrometry. Good agreement was obtained between the M(r)-values measured by
      mass spectrometry and those calculated from the sequences. Five of the sequenced
      proteins contain two copies of a previously observed 18-residue sequence motif,
      while a couple of the remaining sequences show similarity to sequences of
      exoskeletal proteins from shrimps and spiders. Only limited similarity to insect
      cuticular proteins was observed.

PMID- 9530822
TI  - Cloning and sequencing of complementary DNA for fatty acid binding protein from
      rainbow trout heart.
AB  - A cDNA encoding a rainbow trout homologue of mammalian heart fatty acid binding
      protein (H-FABP) was isolated. The deduced protein sequence is 75% identical to
      that of rat H-FABP. The structural conservation of H-FABPs and their evolutionary
      relationship are discussed.

PMID- 9530821
TI  - Pertussis toxin-sensitive GTP-binding proteins characterized in synaptosomal
      fractions of embryonic avian cerebral cortex.
AB  - Pertussis toxin (PTX)-sensitive GTP-binding proteins (G proteins) are essential
      intermediaries subserving neuronal signal transduction pathways that regulate
      excitation-secretion coupling. Despite this established role, relatively little
      is known regarding the identity, subcellular distribution, and relative abundance
      of this class of G proteins in synaptic nerve endings. Here, sucrose density
      gradient centrifugation was combined with 1- and 2-dimensional gel
      electrophoresis to characterize PTX-sensitive G protein alpha subunits in
      synaptosomal fractions of embryonic (day 12) chick cerebral cortical homogenates.
      These findings demonstrate multiple isoforms of M(r) 40-41 kDa Gi alpha and G(o)
      alpha subunits that can be identified on the basis of PTX-catalyzed ADP
      ribosylation and immunoblot analysis.

PMID- 9530823
TI  - Inhibitor and temperature effect on catalase in the liver of adult diploid and
      haploid Rana rugosa.
AB  - The authors succeeded in raising a single mature haploid Rana rugosa female to
      the age of 2 years from an egg artificially fertilized with ultraviolet
      irradiated sperm. In order to discover why this particular haploid individual
      should survive so long, hydrogen peroxide detoxifying catalase in the liver of
      this individual and age-matched diploids was examined and compared for total
      activity, temperature stability, and chemical inhibition. Total activity was
      found to be significantly higher in the haploid frog than in the diploids,
      suggesting that this particular haploid had a unique system for hydrogen peroxide
      detoxification which protected the liver against cell death, preventing hepatic
      failure, and leading to a prolonged survival. Liver catalase from the haploid
      proved to be more labile to aminotriazole and urea, losing 60-70% of its original
      activity after 30 min treatment, whereas diploid catalase lost only 40% under the
      same conditions. Haploid and diploid catalase responded similarly to heat,
      however. It seems likely that inhibitor-binding sites differ considerably between
      the catalase of normal diploids and the catalase of this particular haploid,
      while overall structure is generally similar.

PMID- 9530824
TI  - The last few milliseconds in the life of a secretory granule. Docking, dynamics
      and fusion visualized by total internal reflection fluorescence microscopy
      (TIRFM).
AB  - We have monitored single vesicles (granules) in bovine adrenal chromaffin cells
      using an optical sectioning technique, total internal reflection fluorescence
      microscopy (TIRFM). With TIR, fluorescence excitation is limited to an optical
      slice near a glass/water interface. In cells located at the interface, granules
      loaded with fluorescent dye can be visualized near to or docked at the plasma
      membrane. Here we give evidence that (1) TIRFM resolves single vesicles and (2)
      the fluorescence signal originates from vesicles of roughly 350 nm diameter,
      presumably large dense core vesicles (LDCVs). (3) Diffusional spread of released
      vesicle contents can be resolved and serves as a convenient criterion for a
      fusion event. (4) We give details on vesicle properties in resting cells, such as
      lateral mobility of chromaffin granules, number density, and frequency of
      spontaneous fusion or withdrawal into the cytoplasm. (5) Upon stimulation with
      high extracellular potassium, TIRFM reports depletion of the 'visible pool' of
      vesicles closest to the plasma membrane within hundreds of milliseconds,
      consistent with previous concepts of a release-ready pool. We conclude that TIRFM
      constitutes an independent assay for pool depletion. TIRFM will allow us to study
      aspects of secretion that have previously been inaccessible in living cells, in
      particular the spatial relations and dynamics of vesicles prior to and during
      exocytosis and re-supply of the near-membrane pool of vesicles.

PMID- 9530825
TI  - Structure of the inactivating gate from the Shaker voltage gated K+ channel
      analyzed by NMR spectroscopy.
AB  - Rapid inactivation of voltage-gated K+ (Kv) channels is mediated by an N-terminal
      domain (inactivating ball domain) which blocks the open channel from the
      cytoplasmic side. Inactivating ball domains of various Kv channels are also
      biologically active when synthesized separately and added as a peptide to the
      solution. Synthetic inactivating ball domains from different Kv channels with
      hardly any sequence homology mediate quite similar effects even on unrelated Kv
      channel subtypes whose inactivation domain has been deleted. The solution
      structure of the inactivating ball peptide from Shaker (Sh-P22) was analyzed with
      NMR spectroscopy. The NMR data indicate a non-random structure in an aqueous
      environment. However, while other inactivating ball peptides showed well-defined
      three-dimensional structures under these conditions, Sh-P22 does not have a
      unique, compactly folded structure in solution.

PMID- 9530826
TI  - Investigating the dielectric effects of channel pore water on the electrostatic
      barriers of the permeation ion by the finite difference Poisson-Boltzmann method.
AB  - In this paper, the finite difference Poisson-Boltzmann (FDPB) method with four
      dielectric constants is developed to study the effect of dielectric saturation on
      the electrostatic barriers of the permeation ion. In this method, the inner shape
      of the channel pore is explicitly represented, and the fact that the dielectric
      constant inside the channel pore is different from that of bulk water is taken
      into account. A model channel system which is a righthanded twist bundle with
      four alpha-helical segments is provided for this study. From the FDPB
      calculations, it is found that the difference of the ionic electrostatic
      solvation energy for wider domains depends strongly on the pore radius in the
      vicinity of the ion when the pore dielectric constant is changed from 78 to 5.
      However, the electrostatic solvation energy of the permeation ion can not be
      significantly affected by the dielectric constant in regions with small pore
      radii. Our results indicate that the local electrostatic interactions inside the
      ion channel are of major importance for ion electrostatic solvation energies, and
      the effect of dielectric saturation on the electrostatic barriers is coupled to
      the interior channel dimensions.

PMID- 9530827
TI  - An efficient procedure for studying pectin structure which combines limited
      depolymerization and 13C NMR.
AB  - A protocol for partial thermally-induced depolymerization of differently
      methoxylated pectin samples is described. The resulting macromolecules have been
      fully characterized with various complementary techniques, such as size exclusion
      chromatography (SEC), potentiometry, viscometry and 13C NMR. Optimum conditions
      afford samples at 50-80% yield with weight-average molecular weights in the 4 to
      20 kDa range. The major fraction of these polysaccharides adopts the random-coil
      conformation and such samples are suitable for 13C NMR structural studies at room
      temperature. The methoxyl distributions of two apple pectin samples with a degree
      of esterification (DE) between 54 and 74% and a citrus pectin (DE, 72%) were
      shown to be random in nature, whereas that of a lightly methoxylated apple pectin
      (DE 39%) was partially blockwise. The carbon relaxation parameters of the
      depolymerized pectins attain asymptotic values for Mw > 4 kDa. The Mw values
      estimated from intrinsic viscosity data with the Mark-Houwink relationship
      reported for native pectins are in good agreement with those obtained by either
      end-group analysis (NMR) or SEC. Thus, all the physicochemical data indicate that
      the secondary structure of the isolated chains of depolymerized pectin is closely
      related to that of the parent polymers. Finally, pectinmethylesterase activity
      towards the depolymerized pectins was similar to that of the untreated samples.

PMID- 9530828
TI  - Red blood cell rouleaux formation in dextran solution: dependence on polymer
      conformation.
AB  - The velocity of rouleaux formation (RF), as previously shown, increases with
      increasing dextran concentration up to a critical concentration (Ca), beyond
      which the addition of dextran reduces the RF velocity (RFV). de Gennes' model for
      polymer solutions suggests that dextrans exist in two conformations: a coil
      structure at low concentrations, which changes to a network beyond a critical
      concentration (C*). In the present study we examined the relation between Ca and
      C* for dextrans of different molecular weight, and found that they coincide. This
      suggests that the change in dextran behavior, from increasing to decreasing RFV,
      occurs when their conformation changes from coil to network. In addition, it has
      been reported that in dilute dextran solutions the intercellular distance (D)
      between RBC in rouleaux increases with the molecular weight of the dextran. We
      found that D correlates with Rf, the end-to-end distance of the polymer molecule,
      and for all dextrans D < or = 1.5 Rf. In accord with de Gennes' Model for
      polymers between surfaces, this corresponds to intercellular interaction with two
      overlapping surface-associated polymer layers, which may extend "tails" to
      interact with the opposing cells.

PMID- 9530829
TI  - The use of absolute refractory period in the estimation of early postmortem
      interval.
AB  - The estimation of the time since death (postmortem interval) is one of the most
      difficult problems in forensic pathology. Most methods currently employed use
      temperature-based algorithms intended to model the cooling of the body after
      death and thus estimate the postmortem interval. These methods are subject to
      considerable inaccuracy but their reliability can be improved if a range of other
      observed criteria such as lividity and rigor are also taken into consideration.
      The aim of the present study was to investigate the feasibility of using the
      absolute refractory period as an adjunct to the estimation of postmortem
      interval. The relationship between the 'postmortem interval' and the 'duration of
      absolute refractory period' was investigated using the rat sciatic nerve. A
      strong correlation between the duration of the absolute refractory period and the
      postmortem interval was observed. When both absolute refractory period and
      temperature were used in conjunction, the strength of this correlation was
      increased.

PMID- 9530830
TI  - Combining a continuous Bayesian approach with grouping information.
AB  - When someone breaks glass a number of tiny fragments may be transferred to that
      person. If the glass is broken in the commission of a crime then these fragments
      may be used as evidence. A Bayesian interpretation of this evidence relies on,
      among other things, the forensic scientist's ability to assess the likelihood
      that the glass recovered from the suspect may have come from more than one
      source. This paper will examine the effect of including this information in the
      interpretation. We envisage working towards a system whereby the information loss
      that occurs during the normal casework activities of sample selection and glass
      fragment grouping is quantified.

PMID- 9530832
TI  - Intra- and inter-observer variation in histological criteria used in age at death
      determination based on femoral cortical bone.
AB  - The microscopic method of age at death determination was introduced by Kerley in
      1965. The method, which relies on the quantification of selected elements in
      cortical bone tissue, has been widely used, and several other researchers have
      modified or added to the method. Yet, very few studies have been carried out
      dealing with the intra- and inter-observer error. Furthermore, when such studies
      have been completed, the statistical tools for assessing variability have not
      been adequate. This study presents the results of applying simple quantitative
      statistics on several counts of microscopic elements as observed on photographic
      images of cortical bone, in order to assess intra- and inter-observer error.
      Overall, substantial error was present at the level of identifying and counting
      secondary osteons, osteon fragments and Haversian canals. Only secondary osteons
      can be reliably identified, precluding the use of osteon fragments and Haversian
      canals. The observers in this study included experienced and inexperienced users
      of the microscopic method, yet the variability was uniformly large for all
      observers, suggesting fundamental problems in definition and identification of
      the structural elements. Until more rigorous definitions of such elements have
      been agreed upon, the use of microscopical methods must be discouraged as a sole
      or uncontrolled method of evaluating age at death.

PMID- 9530833
TI  - Fatal overdose of olanzepine.
AB  - An ingestion of an unknown quantity of Zyprexa (olanzapine) tablets in a suicide
      is described. Biological fluid samples obtained at autopsy were analyzed for the
      presence of olanzapine by gas chromatography equipped with nitrogen-phosphorous
      detector and gas chromatography/mass spectroscopy. The blood concentration of
      olanzapine was 490 micrograms/dl and the concentration in gastric contents was
      4100 micrograms/dl.

PMID- 9530831
TI  - Genetic and alkaloid analysis of Papaver species and their F1 hybrid by RAPD,
      HPLC and ELISA.
AB  - Total DNA was extracted from the leaves of a F1 hybrid and its parents, Papaver
      bracteatum Lindle and P. pseudo-orientale Medw. Analysis of random-amplified
      polymorphic DNA (RAPD) using ten arbitrary oligonucleotide 10-mers, showed that
      F1 hybrid was confirmed to be genetically intermediate of both parental plants
      compared with the genetic distance between F1 hybrid and individual parents.
      Furthermore, the comparison of the band patterns between a F1 hybrid, P.
      bracteatum and P. pseudo-orientale clearly showed that part of the bands of both
      parents were induced into a F1 hybrid. The content of thebaine was determined by
      HPLC and ELISA used anti-thebaine monoclonal antibody.

PMID- 9530834
TI  - Persistence of orientation toward a temporarily invisible landmark in Drosophila
      melanogaster.
AB  - In arena experiments with the walking fruit fly, we found a remarkable
      persistence of orientation toward a landmark that disappeared during the fly's
      approach. The directional stability achieved by 'after-fixation' allows a fly to
      continue pursuit under natural conditions, where a selected target is frequently
      concealed by surrounding structures. The persistence of after-fixation was
      investigated in Buridan's paradigm, where a fly walks persistently back and forth
      between two inaccessible landmarks. Upon disappearance of a selected target, the
      flies maintained their intended course for more than 15 body lengths of
      approximately 2.5 mm in about 50% of the trials. About 13% even exceeded 75 body
      lengths. About 88% of the approaches clustered in equal portions around peaks at
      2.4 s and 8.6 s. About 12% of the approaches persisted even longer. In contrast,
      a single peak at about 2.2 s is sufficient to describe the persistence of
      orientation in a random walk. The ability to pursue an invisible landmark is
      disturbed neither by a transient angular deviation from the course toward this
      landmark, when this target disappeared, nor by a distracting second landmark.
      Accordingly, after-fixation seems to require an internal representation of the
      direction toward the concealed target, and idiothetical course control to
      maintain this direction.

PMID- 9530835
TI  - Robust circadian rhythmicity of Drosophila melanogaster requires the presence of
      lateral neurons: a brain-behavioral study of disconnected mutants.
AB  - Mutations at the disconnected (disco) locus of Drosophila melanogaster disrupt
      neural cell patterning in the visual system, leading to the loss of many optic
      lobe neurons. Drosophila's presumptive circadian pacemaker neurons--the dorsal
      and ventral lateral neurons--are usually among the missing cells, and most disco
      flies are behaviorally arrhythmic. In this study, I show that ventral lateral
      neurons (LNvs) are occasionally present and provoke robust circadian rhythmicity
      in disco mutants. Of 357 individual disco flies four animals with robust
      circadian rhythmicity were found. All four retained LNvs together with terminals
      in the superior protocerebrum. Residual or bi-circadian rhythmicity was found in
      about 20% of all flies; the remaining flies were completely arrhythmic. One of
      the flies with residual rhythmicity and two of the arrhythmic flies also had some
      LNvs stained. However, these flies lacked the LNv fibers in the superior
      protocerebrum. The results suggest that the presence of single LNvs is sufficient
      to provoke robust circadian rhythmicity in locomotor activity if the LNv
      terminals reach the superior protocerebrum. The presence of residual or bi
      circadian rhythmicity in 20% of the flies without LNvs indicates that also other
      cells contribute to the rhythmic control of locomotor activity.

PMID- 9530836
TI  - The effect of pulse repetition rate, pulse intensity, and bicuculline on the
      minimum threshold and latency of bat inferior collicular neurons.
AB  - This study examines the effect of pulse repetition rate (PRR), pulse intensity,
      and bicuculline on the minimum threshold (MT) and latency of inferior collicular
      neurons of the big brown bat, Eptesicus fuscus, under free-field stimulation
      conditions. It tests the hypothesis that changes in MT and latency of collicular
      neurons are co-dependent on PRR. The number of impulses in inferior collicular
      neurons (n = 245) increased either monotonically (25%) or non-monotonically (75%)
      with pulse intensity. Latencies either decreased to a plateau (72%), fluctuated
      unpredictably within 3 ms (21%) or changed very little (7%) with increasing pulse
      intensity. Latencies and MTs of most collicular neurons increased by 1.5-24 ms
      (mean +/- SD = 4.8 +/- 3.3 ms) and 4-75 dB (mean +/- SD = 22.1 +/- 16.2 dB) with
      increasing PRR. In most neurons (94%), the latency increase was completely (42%)
      or partially (52%) eliminated when pulse intensity was compensated for the MT
      increase with PRR. Complete elimination of latency was achieved by bicuculline
      application. In a few neurons (6%), the latency increase with PRR was not
      affected by compensated pulse intensity or bicuculline application.

PMID- 9530837
TI  - Spatial transformation of semicircular canal signals into abducens motor signals.
      A comparison between grass frogs and water frogs.
AB  - The spatial transformation of semicircular canal signals to extraocular motor
      signals was studied by recording abducens nerve responses in grass and water
      frogs. Both species have similar vestibular canal coordinates but dissimilar
      orientations of their optic axes. Before sinusoidal oscillation in darkness the
      static head position was systematically altered to determine the planes of head
      oscillation in pitch and roll associated with minimal abducens nerve responses.
      Measured data and known canal plane vectors were used to calculate the abducens
      response vector in canal coordinates. The abducens vector deviated from the
      horizontal canal plane vector in grass frogs by 15 degrees and in water frogs by
      34 degrees but was aligned with the pulling direction of the lateral rectus
      muscle in each of the two species. Lesion experiments demonstrated the importance
      of convergent inputs from the contralateral horizontal and anterior semicircular
      canals for the orientation of the abducens response vector. Thus, the orientation
      of the optic axis and the pulling directions of extraocular muscles are taken
      into account by the central organization of vestibulo-ocular reflexes. Horizontal
      and vertical canal signals are combined species-specifically to transform the
      spatial coordinates of sensory signals into appropriate extraocular motor
      signals.

PMID- 9530838
TI  - Activity pattern of an oscillatory network after synaptic block in the leech
      central nervous system.
AB  - The activity of heart interneurons (HN cells) and heart motor neurons in the
      central nervous system of the medicinal leech was recorded intracellularly from
      their cell bodies in the third and fourth segmental ganglion (G3 and G4,
      respectively). Reciprocal inhibitory synaptic transmission between HN cells in
      the G3 was blocked by photoinactivation of neuropil glial cells in the same
      ganglion. The block disrupted the alternating rhythmic spike activity of HN cells
      in the G3 in isolated G3s but not in chains of G3 and G4. In the latter case, the
      rhythmic spike pattern of HN cells in the G3 appears to originate in the G4
      because, for example, severing one connective between the G3 and G4 silenced the
      ipsilateral heart interneuron in the G3, whereas its contralateral homologue
      remained rhythmically active. Simultaneous recordings from HN cells in the G3 and
      G4 suggest that the latter may serve to coordinate the rhythmic activity of HN
      cells in the G3, when synaptic interaction between HN cells in the G3 is blocked.
      This study reveals a considerable capacity of the neural network controlling the
      heart beat to compensate for the impairment of synapses within one ganglion.

PMID- 9530839
TI  - Consistency of interneuronal group formation in response to stimulation of
      identified cells.
AB  - In crayfish stimulation of abdominal positioning interneurons (APIs) recruits
      other interneurons producing various abdominal movements. We investigated
      whether: (1) the same API from different preparations activated a similar number
      or group of interneurons, (2) different APIs activated different groups, and (3)
      repeated stimulation of an API consistently affected a similar set of
      interneurons. To quantify the similarities and differences of the recruited
      interneuronal groups we compared the number of interneurons affected, their
      firing frequencies, and motor outputs. Three types of APIs (Curly Q, L and T)
      were identified and each type was stimulated in three preparations. Our results
      showed that for the Curly Q and L cells, each cell type activated interneuronal
      groups that were statistically similar in number and firing frequency. The T cell
      activated interneuronal groups that were more variable. Some APIs generally
      provided a repeatable motor output; all did not. The interneuronal groups
      activated by the Curly Q, L and T cells were very different from each other.
      Repeated stimulation of one Curly Q cell affected similar although not identical
      sets of interneurons. These data suggest that repeated motor outputs could be
      produced by a similar but not identical group of cells.

PMID- 9530840
TI  - The coordination and interaction between respiration and deglutition in young
      pigs.
AB  - The anatomical pathways for inspired air and ingested food cross in the pharynx
      of mammals, implying that breathing and swallowing must be separated either in
      space or in time. In this study we investigated the time relationship between
      swallowing and respiration in young pigs, as a model for suckling mammals.
      Despite the high morphological position of the larynx in young mammals, allowing
      liquid to pass in food channels lateral to the larynx, respiration and swallowing
      are not wholly independent events. Although, when suckling on a veterinary teat,
      the swallows occurred at various points in the respiratory cycle, there was
      always a period of apnea associated with the swallow. Finally, an increase in the
      viscosity of the milk altered this coordination, changing respiratory cycle
      length and also restricting the relative rate at which swallows occurred in some
      parts of the respiratory cycle. These results suggest that the subsequent changes
      in respiratory activity at weaning, associated with passage of a solid bolus over
      the larynx, is preceded by the ability of the animal to alter coordination
      between respiration and swallowing for a liquid bolus.

PMID- 9530842
TI  - Output loss or rehearsal loop? Output-time versus pronunciation-time limits in
      immediate recall for forgetting-matched materials.
AB  - Forgetting during recall may be one limit on memory span. Output time and
      accuracy of immediate serial recall using spoken and keypress responses were
      measured for digit, letter, and word sets approximately matched in phonemic
      discriminability and in immediate recognition memory. Nonetheless, the materials
      differed from one another in recall span, in output time during recall, and in
      pronunciation time (speech rate). Recall output times accounted precisely and
      completely for the measured memory span for these matched materials.
      Pronunciation times are correlated with recall output times, but output time
      gives a slightly better account of recall accuracy. The output time equivalent to
      the rule that short-term memory span corresponds to the number of items that can
      be said in about 1.5-2 s is that span corresponds to the number of items that can
      be recalled in about 4-6 s. Additional variations in span reflect differential
      item interference.

PMID- 9530843
TI  - Event-based prospective memory and executive control of working memory.
AB  - In 5 experiments, the character of concurrent cognitive processing was
      manipulated during an event-based prospective memory task. High- and low-load
      conditions that differed only in the difficulty of the concurrent task were
      tested in each experiment. In Experiments 1 and 2, attention-demanding tasks from
      the literature on executive control produced decrements in prospective memory. In
      Experiment 3, attention was divided by different loads of articulatory
      suppression that did not ultimately lead to decrements in prospective memory. A
      high-load manipulation of a visuospatial task requiring performance monitoring
      resulted in worse prospective memory in Experiment 4, whereas in Experiment 5 a
      visuospatial task with little monitoring did not. Results are discussed in terms
      of executive functions, such as planning and monitoring, that appear to be
      critical to successful event-based prospective memory.

PMID- 9530841
TI  - Are false recognitions influenced by prerecognition processing?
AB  - Lexical activation is a core process in models of spoken word recognition.
      Specific words activated are candidates, with degree of activation determined by
      the match with sensory information. Once identified, lexical activation shifts to
      provide a meaningful representation, normally through activation of semantically
      related words. Activated words are assumed to acquire familiarity as a result of
      being activated, providing a basis for memories, both real and imagined. Three
      experiments showed a direct relationship between number of false recognitions and
      their presumed degree of activation. Results converge with those from spoken word
      recognition in implicating lexical activation during early stages of processing.
      For recognition memory, the message is that prerecognition lexical processing
      should be included in the memory equation.

PMID- 9530844
TI  - The revelation that the revelation effect is not due to revelation.
AB  - The revelation effect is the tendency to call an item on a recognition test "old"
      if it is preceded by a different task interpolated between study and test. Seven
      experiments explored the generality of the revelation effect across a number of
      interpolated tasks. A revelation effect emerged when a variety of tasks preceded
      recognition test items; the effect was found for test items that followed a
      memory-span task, a synonym-generation task, and a letter-counting task. The
      compatibility between the test stimuli and the stimuli that composed the
      interpolated task was found to be a critical factor. With words as stimuli on a
      recognition test, a revelation effect was found when the stimuli in the
      interpolated task were words and letters. However, when numbers were the stimuli
      in the interpolated task, no revelation effect was found.

PMID- 9530845
TI  - Phonological codes and eye movements in reading.
AB  - A number of recent studies using eye movement data have yielded evidence
      suggesting that phonological codes are activated early in an eye fixation.
      However, experiments reported by M. Daneman and E. Reingold (1993; M. Daneman, E.
      M. Reingold, & M. Davidson, 1995) yielded data that led them to argue that
      phonological codes are primarily activated after lexical access has occurred. In
      this study, 3 experiments were carried out that were conceptually similar to
      those of M. Daneman and E. Reingold, and the resulting data supported the
      position that phonological codes are activated very early in an eye fixation.

PMID- 9530846
TI  - The prime lexicality effect: form-priming as a function of prime awareness,
      lexical status, and discrimination difficulty.
AB  - G. W. Humphreys, D. Besner, and P. T. Quinlan (1988) found that form-primes
      (e.g., contrast-CONTRACT) were effective only with masked primes. C. Veres (1986)
      obtained the same effect for word primes but found that nonword primes (e.g.,
      controct) were effective regardless of masking. In a lexical-decision task, the
      present study failed to find any priming with word primes but only when the
      nonword distractors were very close to a particular word (e.g., UNIVORSE). With
      more distant nonword distractors (e.g., ANIVORSE), priming with word primes was
      restored in the masked condition. In terms of an entry-opening model of priming,
      this effect was interpreted as a blocking of priming by a postaccess checking
      operation. Alternatively, in an interactive activation model, this effect could
      be modeled either by decreasing the strength of lexical competition or by
      changing the decision criterion from local to global activation.

PMID- 9530847
TI  - Real age-of-acquisition effects in lexical retrieval.
AB  - Previous research on the effects of age of acquisition on lexical processing has
      relied on adult estimates of the age at which children learn words. The authors
      report 2 experiments in which effects of age of acquisition on lexical retrieval
      are demonstrated using real age-of-acquisition norms. In Experiment 1, real age
      of acquisition emerged as a powerful predictor of adult object-naming speed.
      There were also significant effects of visual complexity, word frequency, and
      name agreement. Similar results were obtained in reanalyses of data from 2 other
      studies of object naming. In Experiment 2, real age of acquisition affected
      immediate but not delayed object-naming speed. The authors conclude that age-of
      acquisition effects are real and suggest that age of acquisition influences the
      speed with which spoken word forms can be retrieved from the phonological
      lexicon.

PMID- 9530848
TI  - The mirror effect and attention-likelihood theory: a reflective analysis.
AB  - The mirror effect refers to findings from studies of recognition memory
      consistent with the idea that the underlying "strength" distributions are
      symmetric around their midpoint separating studied and nonstudied items.
      Attention-likelihood theory assumes underlying binomial distributions of marked
      features and claims that old-item differences result from differential attention
      across conditions during study. The symmetry arises because subjects use the
      likelihood ratio as the basis for decision. The author analyzes the model and
      argues that one of the main criticisms (the complexity of the likelihood-ratio
      decision rule) is unwarranted. A further analysis shows that other distributions
      (the Poisson and the hypergeometric) can also produce a mirror effect. Even with
      the binomial distribution, a variety of parameter values can produce a mirror
      effect, and with the right combination of parameter values, differential
      attention across conditions is not necessary for a mirror effect to occur.

PMID- 9530849
TI  - Structure determines function of the retina, a neural center. 1. The synaptic
      ribbon complex.
AB  - A new approach to study the function of the retina is described. It involves a
      precise revealing of synaptic connections between the neurons by means of three
      dimensional volume reconstructions. Identification of several hundreds of
      synapses revealed the existence of groups of synaptically interconnected neurons
      constituting discrete neural circuits accounting for processing of information
      contributed by the photoreceptors. Supplementary information contributed by
      electrophysiological recordings of membrane potentials of neurons in these
      circuits made it possible to determine how information is processed by the
      circuits. Two versions of one of the circuits are analyzed in this communication.

PMID- 9530850
TI  - Ultrastructure of blood vessel regression in involution of foreign-body
      granuloma.
AB  - The diversity of endothelial cell deletion in regressing blood vessels during
      involution of granulation tissue was investigated in foreign-body granulomas
      induced by a collagen sponge implanted into the dorsum of the rat. Small blood
      vessel density counts were performed to determine the degree of blood vessel
      regression in the involution of granulation tissue in foreign-body granuloma. The
      density of these small blood vessels significantly decreased between 100 and 130
      days after sponge implantation. The detachment of endothelial cells from their
      underlying basement membrane and the consequent protrusion into and/or out of the
      lumen in the vascular network of granulation tissue was observed by electron
      microscopy. Based on the pattern of manifestation in the endothelium and the
      characteristic deformation of nuclei, the detached endothelial cells were
      classified into two groups: 1) the endothelial cell apoptosis group and 2) the
      endothelial cell degeneration group. The essential difference between the two
      groups was easily distinguishable as the nucleus of the former group displayed
      chromatin condensation and margination as the hallmark of early apoptotic
      changes, while the nucleus of the latter group displayed a pinch structure and
      intranuclear pocket formation. However, the process by which the detached
      endothelial cells were shed into the vascular lumen and eventually eliminated
      from circulation was the same in both groups. The occurrence of both groups
      increased on the 90th day after sponge implantation and reached a maximum on the
      110th day, indicating that the appearance of the groups was synchronized. These
      results suggest that the two major processes of apoptosis and degeneration of
      endothelial cells occur during endothelial cell deletion as a mechanism
      contributing to blood vessel regression.

PMID- 9530851
TI  - Modulation of vesicle shedding in 8701 BC human breast carcinoma cells.
AB  - Vesicles, shed in the extracellular medium by several kinds of normal and tumoral
      cells, are known to play important roles in cell-cell and cell-matrix
      interactions and to participate in mechanisms by which tumoral cells acquire
      metastatic capability and evade immune surveillance. Regulation of the shedding
      phenomenon and molecular mechanisms involved in extracellular vesicle production
      are not known and are the subject of this investigation. Fetal calf serum
      stimulated shedding short after its addition and its stimulatory effect was dose
      dependent. This effect was reduced after gelatin-Sepharose adsorption indicating
      a possible involvement of gelatinases on its stimulatory effect. This conclusion
      was confirmed by the inhibitory effect of bathophenanthroline. Shedding of
      membrane vesicles decreased after treatment with all trans retinoic acid, a
      molecule known for its capability to induce cell differentiation. Brefeldin A, an
      inhibitor of intracellular vesicle movements, and methylamine, an inhibitor of
      exocytosis, did not abolish shedding. Quercetin, an inhibitor of phosphatidyl
      inositol 4 kinase and 1,4 phosphatidyl inositol 5 kinase, and 8-Cl-cAMP, a site
      selective cAMP analogous which induces growth inhibition and differentiation,
      significantly decreased the amount of shed vesicles.

PMID- 9530853
TI  - Ultrastructural and freeze fracture cilia morphology of trachea epithelium in
      apparently healthy small ruminants.
AB  - Specimens of tracheal mucosa were obtained from ten adult apparently healthy
      small ruminants (five goats and five sheep) both by a fibre optic endoscope and
      in a slaughterhouse. Ultrastructurally, a total of 50,000 cilia were examined.
      Pathological cilia were found in all examined subjects. The prevalence of
      compound cilia showed a range of 0.3% to 3%. Intracytoplasmic and swollen cilia
      ranged from 0.2% to 0.5%. The microtubular pattern was examined in 4,000 cross
      sectioned cilia and an abnormal pattern was found in 5-7%. Microtubular defects
      involved both peripheral and central doublets, being peripheral abnormalities the
      prevailing ones. A central plug of electron dense material was observed in 2-3%
      of the examined basal bodies. Rare basal bodies characterized by an abnormal
      spatial configuration were also shown. Freeze fracture studies revealed a ciliary
      necklace composed of 4 to 5 rows of intramembrane particles.

PMID- 9530854
TI  - Ultrastructural and immunocytochemical study on the infection of enterovirus 71
      (EV 71) in rhabdomyosarcoma (RD) cells.
AB  - Rhabdomyosarcoma monolayers were inoculated with enterovirus 71 (EV 71) at 73
      degrees C, sampled at intervals during the replicative cycle, and examined in
      thin sections by electron microscopy, using routine and immunoelectronmicroscopy
      with polyclonal antibodies against EV 71. The location of EV 71 or its precursors
      was followed during the viral replicative cycle. The earliest samples (3 h
      postinoculation) showed a cell shape change, from elongated to rounded. At 6 h
      postinoculation, the presence of early virus-induced vesicles developing within
      the cytoplasm was pointed out, although no virus particles were observed at these
      stages. At 12 and 20 h postinoculation, virus particles appeared in the
      cytoplasm. They were found free or in clusters in the cytoplasmic matrix, between
      the virus-induced vesicles. EV 71 particles were also occasionally observed in
      the form of paracrystalline arrays situated in the vesiculated areas. The
      immunolabel (gold beads) was found, initially, over dense cytoplasmic areas and
      in more advanced process at the vesiculated area and over the virus particles.
      Therefore the main cellular alterations observed in this infection were the shape
      change of the cell and the appearance of electron-dense areas (viroplasm) and
      smooth walled vesicles which are probably the site of the virus replication.

PMID- 9530855
TI  - Ultrastructural study of the lateral lobe of the prostate of Wistar rats
      submitted to experimental chronic alcohol ingestion.
AB  - Alcoholism is considered today one of the most serious social and medical
      problems. Different investigators have demonstrated that chronic exposure to
      alcohol causes morphological and physiological changes in the testes and in the
      accessory sex glands, in the prostate in particular. In the present study,
      experimental rats were divided into groups receiving sugar cane brandy diluted to
      30 degrees G.L. (30%, v/v) and Purina ration ad libitum for 60, 120, 180, 240 and
      300 days, respectively. At the end of each period the animals were sacrificed and
      the lateral lobe of the prostate was collected for histological examination. The
      results showed atrophied epithelium, accumulation of lipidic droplets and rupture
      of the microvilli that line the cell surface facing the lumen of cells of the
      secretory epithelium of the lateral lobe of the prostate.

PMID- 9530857
TI  - Myocardial interatrial septum loses its epithelial organization by mesenchymal
      influence. Structural and ultrastructural study.
AB  - During atrial septation, the septum primum fuses with the atrioventricular
      endocardial cushions and myocardial-mesenchymal interactions occur. In order to
      evaluate the cellular events that take place during this particular interaction a
      structural, ultrastructural and histochemical study was performed. Our findings
      indicate that from the fourth day of development, the distal myocardium of the
      interatrial septum, which interacts with mesenchymal tissue, loses its appearance
      of an epithelial sheet and becomes a loosely organized tissue. The distal
      myocytes of the interatrial septum which get progressively separated show
      features of migratory cells, the final localization of which is the mesenchymal
      tissue of the adjacent endocardial cushions. These tissue changes involve basal
      membrane disruption, reduction in the number of desmosomes and intercalated discs
      with the subsequent appearance of large intercellular spaces between myocytes,
      myofibrillar disarrangement and acquisition by myocytes of a secretory phenotype
      characterized by numerous cytoplasmic vesicles. These events occur in a similar
      way in the atrioventricular canal, where a myocardial-mesenchymal interaction
      also occurs. In both regions the mesenchymal endocardial cushions and its
      associated extracellular matrix seem to direct the dissociation of the myocardial
      tissue and the subsequent migratory cellular behaviour of the interacting
      myocytes. This is an interesting, and little known, example of a cellular
      phenotypic transformation during cardiac development.

PMID- 9530858
TI  - Apoptosis-like changes in the lungs induced by cyclophosphamide and papain. I. An
      ultrastructural study.
AB  - An ultrastructural study was made to analyze the structural and cellular features
      of the pulmonary lesions produced in Wistar rats by the administration of
      cyclophosphamide (CP) and/or papain (P). Combined administration of
      cyclophosphamide and papain caused severe damage to lung tissue including
      necrosis, particularly to alveolar epithelial and endothelial cells. Some of the
      damaged type II cells showed nuclear and cytoplasmic features that are considered
      indicative of apoptosis. Apoptosis-like changes were also observed in endothelial
      and mesenchymal cells in the interstitium of interalveolar septa. Phagocytosis of
      apoptotic bodies by macrophages was found too. Apoptosis-like changes were not
      revealed in those areas of lung tissue where fibroplasia processes prevailed. Nor
      were they observed in the animals receiving papain only. Occasionally apoptosis
      like changes were found in type II cells and in endothelial cells in rats given
      cyclophosphamide only. The results obtained also suggest the possibility of
      active participation of type II alveolar epithelial cells in the fibroplasia
      process in the course of lung rebuilding in acute lung tissue damage induced with
      simultaneous administration of cyclophosphamide and papain.

PMID- 9530859
TI  - A role of SH-compounds in maturation of melanosomes in cells cultured from nevus
      Ota.
AB  - A role of SH-compounds such as cysteine and glutathione in melanogenesis in
      dermal melanocytes cultured from Ota's nevus tissue was demonstrated in relation
      to another substrate, dihydroxyphenylalanine (DOPA). Chemical analysis of
      eumelanin and pheomelanin was performed in addition to the conventional electron
      microscopic observation. Supplements of the culture medium with each of these
      compounds separately for two weeks gave rise to the formation of pre
      pheomelanosomes and secondary lysosomes or myelinosome-like inclusions. When DOPA
      and glutathione were added to the medium together, the maturation of melanosomes
      was promoted. This was proven by the increase in electron-density of pre
      melanosomes observed as well as by the content of pheomelanin and eumelanin.
      However, mature melanosomes were not formed when each of these chemicals was
      added to the medium individually for the same periods. The melanosome maturation
      seemed to occur via a process involving secondary lysosomes or myelinosomes, in
      which more electron-dense particles accumulated in the presence of both reagents.
      The pheomelanosomal process was also observed, but typical eumelanosome-related
      processes were not observed in this culture system.

PMID- 9530860
TI  - Role of basic fibroblast growth factor in the formation of the capillary plexus
      in the chick embryo chorioallantoic membrane. An in situ hybridization,
      immunohistochemical and ultrastructural study.
AB  - The chick embryo chorioallantoic membrane (CAM) is supplied by an extensive
      capillary network. We have previously demonstrated that a Mr 16,000 basic
      fibroblast growth factor (FGF2)-like molecule is present in the CAM. At present,
      no data are available on the cellular source(s) of FGF2 in the CAM. In this work,
      CAM has been investigated by in situ hybridization with the aim to identify the
      source(s) of endogenous FGF2 during development. The immunohistochemical
      expression of fibronectin, laminin and type IV collagen in the CAM extracellular
      matrix (ECM) and the ultrastructural relationships between chorionic epithelium
      and the underlying capillary plexus were also studied. Our findings strongly
      suggest that FGF2 regulates the development of the capillary plexus by two
      sequential steps. In an early paracrine phase, chorionic epithelial cells secrete
      FGF2, thus eliciting an angiogenic response in the undifferentiated mesodermal
      blood vessels. In response to this paracrine signalling, the newly formed
      endothelial cells move through a permissive ECM and migrate beneath the chorion.
      Here, they synthesize an autocrine supply of FGF2 necessary to further
      proliferate and differentiate, thus originating the capillary plexus.

PMID- 9530861
TI  - Ultrastructural and immunohistochemical observations concerning laminin in B16
      melanoma. Is an amorphous form of laminin promoting a non hematogenous migration
      of tumor cells?
AB  - The gravity of cancer is related to the propensity of tumor cells to migrate from
      a primary site to distant organs. It is generally accepted that tumor migration
      occurs in the vascular stream, via the endothelial basement membrane or lamina. A
      recent study identified in human malignant melanomas an angio-tumoral association
      (termed the angio-tumoral complex) characterized by an amorphous material
      juxtaposed between endothelial cells and tumor cells that contained laminin. The
      absence of any sign of intravasation and the pericytic location of tumor cells in
      this typical image raised the question of the role of these complexes in
      promoting tumorigenesis. Using the mouse B16 melanoma model, we observed an
      increase of angio-tumoral complexes with tumor progression, again without any
      evidence of intravasation. Given the role of laminin in migration and metastasis,
      we discuss a non hematogenous mechanism of tumor migration along the abluminal
      surface of endothelium.

PMID- 9530862
TI  - Electron microscopic analysis of cortical biopsies in patients with traumatic
      brain injuries and dysfunction of neurobehavioural system.
AB  - Cortical biopsies of eight patients with craniocerebral trauma complicated with
      subdural or epidural hematoma were examined with the transmission electron
      microscope. The patients showed post-traumatic neurobehavioural disorders and
      moderate or severe vasogenic brain edema. The capillary wall displayed increased
      vacuolar and vesicular endothelial transport, basement membrane thickening and
      vacuolization and swollen astrocytic end-feet. Pericapillary and parenchymatous
      hemorrhages were also observed. The extracellular space appeared considerably
      enlarged with presence of proteinaceous hematogenous edema fluid and fibrinous
      organization. Pyramidal and non-pyramidal neurons showed intracellular edema
      featured by irregular enlargement of rough endoplasmic reticulum, nuclear
      envelope and Golgi apparatus. The myelinated axons exhibited clear or black type
      axoplasmic degeneration, varicose fiber swelling, myelin sheath distortion,
      formation of myelin ovoids and increased amount of oligodendroglial ad-axonal
      layer. The dendrites also showed clear or dark and beaded shape degeneration.
      Synaptic degeneration was characterized by swollen and shrunken pre- and
      postsynaptic endings, clumping, enlargement and depletion of synaptic vesicles,
      synaptic membrane complex disassembly and detachment of glial ensheathment.
      Perivascular and perineuronal astrocytes appeared remarkably swollen. Phagocytic
      astrocytes were also found. Oligodendrocytes displayed hydropic and reactive
      changes. Reactive oligodendrocytes induced myelinolysis. The brain barrier
      dysfunction, the vasogenic and cytotoxic edema and the subsequent neuronal and
      neuroglial cell reactive and degeneration processes might represent the
      morphological substrate responsible for the post-traumatic neurobehavioural
      disorders.

PMID- 9530863
TI  - Interaction of PCB congeners and 2,3,7,8-TCDD in the rat liver: an electron
      microscope study.
AB  - Polyhalogenated aromatic compounds such as polychlorinated biphenyls (PCBs) and
      polychlorinated dibenzo-p-dioxins continue to be environmental contaminants
      because of their bioaccumulation in the food chain and resistance to
      biodegradation. This study was undertaken to determine if WHO-IPCS PCB congeners
      or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) individually or their
      coadministration in rats produced morphological alterations in the liver. Groups
      (N = 5) of female Sprague Dawley rats received TCDD (0, 2.5, 25, 250, 1,000 ng/kg
      bw/day) or PCB (0, 2, 20 micrograms/kg bw/day) either alone, or each dose of PCB
      coadministered with that of TCDD. The test substances were dissolved in corn oil
      and given by gavage at 0.2 ml/100 g bw/day for 28 days. At the end of the
      experiment the rats were killed and liver samples were prepared for transmission
      electron microscopy. Electron micrographs of the liver from animals of the
      control groups revealed characteristic normal hepatocyte architecture. An
      increase in smooth endoplasmic reticulum (SER) profiles and a corresponding
      decrease in the profiles of rough endoplasmic reticulum (RER) proportional to the
      increased doses of the compounds was revealed in the micrographs.
      Coadministration of PCBs and TCDD induced greater SER proliferation and a greater
      decrease in the number of RER profiles compared to either compound administered
      individually. The PCBs and TCDD at the doses used apparently interacted to induce
      hepatic ultrastructural alterations. These changes may represent an attempt by
      the organism to metabolize and neutralize the effects of xenobiotics.

PMID- 9530865
TI  - Supraependymal neuronal elements of the floor of the fourth ventricle in adult
      rat: a scanning electron microscopic study.
AB  - Scanning electron microscopic studies of the floor of the fourth ventricle
      revealed the presence of a cluster of neuron-like structures and an extensive
      network of fibers on the ependymal surface. These supraependymal cell clusters
      are found on the sparsely ciliated regions of the fourth ventricle. The surface
      of these cells is richly covered with nerve ending-like structures of varying
      size and shape. Long cables of intertwined fibers are present all over the
      surface of the fourth ventricular floor. Majority of these fibers are varicose in
      nature. Some of these fibers end blindly as round or ellipsoid thickening in the
      ventricular cavity. The widespread occurrence of supraependymal structures of the
      third and fourth ventricles, which are presumed to be neurons, nerve fibers and
      free floating nerve endings in the cerebrospinal fluid (CSF), suggest that they
      potentially function as an additional of intraventricular communication.

PMID- 9530864
TI  - Subacute combined degeneration in totally gastrectomized rats: an ultrastructural
      study.
AB  - Severe permanent cobalamin (Cbl) deficiency was induced in rats either by total
      gastrectomy (TG) or through prolonged dietary Cbl deprivation. This paper deals
      with an ultrastructural investigation of different parts of the central nervous
      system (CNS) of rats made Cbl-deficient through one of these of two procedures.
      In both totally gastrectomized (TGX) rats and in rats chronically fed a Cbl
      deficient diet, we observed intramyelin edema, with splitting of the lamellae,
      and interstitial edema affecting the white matter, mainly in the spinal cord
      (SC). These lesions were also present in the subcortical white matter, although
      to a lesser degree. In both TGX-rats and in rats chronically fed a Cbl-deficient
      diet the pyramidal tract and the optic nerve were completely spared. Vascular
      lesions were never observed. Intramyelin edema and interstitial edema of the
      white matter account for the patchy myelopathic spongy vacuolation, which is the
      histological hallmark of human subacute combined degeneration and has been
      previously seen in SC white matter of TGX-rats. Macro- and micro-glial cells in
      the white matter were activated, at least as seen ultrastructurally.
      Interestingly enough, there were activated glial cells even in the gray matter,
      in which neurons showed absolutely no alterations. Chronic subcutaneous Cbl
      administration of TGX-rats partially repaired the CNS damage. However, the
      amelioration produced by this treatment was greater when Cbl was given shortly
      after TG than when given three and four months after TG, i.e. when the lesions
      have already been formed.

PMID- 9530866
TI  - Identification of R-gene homologous DNA fragments genetically linked to disease
      resistance loci in Arabidopsis thaliana.
AB  - Disease resistance in plants is a desirable economic trait. A number of disease
      resistance genes from various plant species have been cloned so far. The gene
      products of some of these can be distinguished by the presence of an N-terminal
      nucleotide binding site and a C-terminal stretch of leucine-rich repeats.
      Although these gene products are structurally related, the DNA sequences are
      poorly conserved. Only parts of the nucleotide binding site share enough DNA
      identity to design primers for polymerase chain reaction amplification of related
      DNA sequences. Such primers were used to amplify different resistance-gene-like
      (RGL) DNA fragments from Arabidopsis thaliana accessions Landsberg erecta and
      Columbia. Almost all cloned DNA fragments were genetically closely linked with
      known disease resistance loci. Most RGL fragments were found in a clustered or
      dispersed multi-copy sequence organization, supporting the supposed correlation
      of RGL sequences and disease resistance loci.

PMID- 9530868
TI  - The exuT gene of Erwinia chrysanthemi EC16: nucleotide sequence, expression,
      localization, and relevance of the gene product.
AB  - Galacturonic acid (GalUA) is a major component of pectin and polygalacturonic
      acid in the plant cell wall. In the phytopathogen Erwinia chrysanthemi, the
      uptake of molecules derived from degradation of these polymers is an important
      early step in the events preceding induction of pectinases, ultimately leading to
      plant tissue maceration. Uptake systems for GalUA and dimers of GalUA have been
      described and shown to be inducible in E. chrysanthemi. The GalUA uptake gene
      (exuT) was cloned and sequenced. Nucleotide sequence analysis identified an open
      reading frame encoding a 345-amino-acid polypeptide with a calculated mass of
      37,825 Da. This polypeptide is predicted to be an integral membrane protein based
      on its high nonpolar amino acid content and hydropathic profile. Localization
      studies with the labeled polypeptide in the T7-RNA polymerase system also suggest
      that ExuT is a membrane protein. This evidence is further supported by the
      observation of hybrid ExuT-PhoA proteins in the bacterial cytoplasmic membrane
      following immunoblot analysis. Northern (RNA) analysis indicated that the gene is
      inducible in the presence of the monomer, GalUA. A targeted mutation in the exuT
      gene affected the utilization of GalUA as a role carbon source for growth.
      Maceration of potato tuber tissue by this mutant was delayed and reduced, when
      compared with the parental strain EC16.

PMID- 9530869
TI  - Characterization of a pepper mild mottle tobamovirus strain capable of overcoming
      the L3 gene-mediated resistance, distinct from the resistance-breaking Italian
      isolate.
AB  - Green pepper plants with the L3 resistance gene usually develop necrotic lesions
      on leaves infected with a Japanese strain of pepper mild mottle tobamovirus
      (PMMoV-J). A recently discovered strain, PMMoV-Ij, has the ability to overcome L3
      resistance. Phytopathological responses of a variety of plant species to PMMoV-J
      and PMMoV-Ij were determined and the coat protein (CP) sequence comparisons
      revealed both amino acids 43 and 50 of PMMoV-Ij were unique. This led us to
      believe that substitutions at these residues would enable PMMoV-J to overcome L3
      resistance. This was confirmed by Western blot (immunoblot) detection of PMMoV-J
      containing both point mutations in upper uninoculated leaves of resistant plants.
      Computer models suggest the critical residues in overcoming resistance lie in CP
      regions that putatively interact with other subunits. These results contribute to
      our understanding of the virus's ability to circumvent plant resistance.

PMID- 9530870
TI  - Assessment of stress fiber orientation during healing of radial keratotomy wounds
      using confocal microscopy.
AB  - Radial keratotomy (RK) is a refractive surgical procedure in which partial
      thickness incisions are made in the cornea in order to alter its shape. Previous
      studies suggest that RK wounds undergo changes in wound gape in response to the
      ingrowth of myofibroblasts which mediate subsequent wound contraction and may
      modulate changes in corneal curvature seen after RK. A recent quantitative
      analysis of f-actin organization in full-thickness incisional wounds in the
      rabbit demonstrated that microfilament bundles (stress fibers) present in
      myofibroblasts align parallel to the long axis of the wound during wound
      contraction. To investigate whether the same pattern of alignment occurs after
      RK, a similar analysis of f-actin organization was undertaken using the cat RK
      model. Radial keratotomy wounds were studied from 10 to 28 days after surgery
      using en block staining with fluorescein isothiocyanate (FITC) phalloidin, and
      three-dimensional (3-D) datasets (z-series of en face optical sections) were
      collected using laser confocal microscopy at various regions within the wound. In
      addition, conventional en face sections were double-labeled using combinations of
      phalloidin and antibodies to fibronectin and alpha 5 beta 1 integrin.
      Myofibroblast ingrowth started in the bottom of the wound and progressed
      anteriorly. At 10 to 14 days, f-actin was predominantly distributed in long,
      thick bundles (stress fibers) within the wound. These fibers appeared to be
      randomly oriented anteriorly, but became progressively more aligned with the long
      axis of the wound posteriorly. At 21 days, the stress fibers were predominantly
      oriented parallel to the long axis of the wound at all levels. F-actin,
      fibronectin and integrin were coaligned at both the 14 and 21 day time points.
      Since the majority of wound closure occurs between 14 and 28 days after surgery,
      we conclude that parallel alignment of the actin filament-fibronectin-integrin
      assembly in the cat RK model is associated with wound contraction.

PMID- 9530871
TI  - Presence of the CO2-concentrating mechanism in some species of the pyrenoid-less
      free-living algal genus Chloromonas (Volvocales, Chlorophyta).
AB  - Physiological and morphological characteristics related to the CO2-concentrating
      mechanism (CCM) were examined in several species of the free-living, unicellular
      volvocalean genus Chloromonas (Chlorophyta), which differs morphologically from
      the genus Chlamydomonas only by lacking pyrenoids. The absence of pyrenoids in
      the chloroplasts of Chloromonas (Cr.) rosae UTEX 1337, Cr. serbinowii UTEX 492,
      Cr. clatharata UTEX 1970, Cr. rosae SAG 26.90, and Cr. palmelloides SAG 32.86 was
      confirmed by light and electron microscopy. In addition, immunogold electron
      microscopy demonstrated that ribulose-1,5-bisphosphate carboxylase/oxygenase
      (Rubisco; EC 4.1.1.39) molecules were distributed almost evently throughout the
      chloroplasts in all five Chloromonas strains. However, Chloromonas exhibited two
      types of physiological characteristics related to the CCM depending on the
      species or strains examined. Chloromonas rosae UTEX 1337 and Cr. serbinowii had
      high photosynthetic affinities for CO2 in cells grown in culture medium bubbled
      with air (low-CO2 cells), compared with those grown in medium bubbled with 5% CO2
      (high-CO2 cells), indicating the presence of the low-CO2-inducible CCM. In
      addition, these two Chloromonas strains exhibited low-CO2-inducible carbonic
      anhydrase (CA; EC 4.2.1.1) activity and seemed to have small intracellular
      inorganic carbon pools. Therefore, it appears that Cr. rosae UTEX 1337 and Cr.
      serbinowii possess the CCM as in pyrenoid-containing microalgae such as
      Chlamydomonas reinhardtii. By contrast, Cr. clatharata, Cr. rosae SAG 26.90 and
      Cr. palmelloides showed low photosynthetic affinities for CO2 when grown under
      both CO2 conditions. Moreover, these three strains exhibited an apparent absence
      of intracellular inorganic carbon pools and lacked low-CO2-inducible CA activity.
      Thus, Cr. clatharata, Cr. rosae SAG 26.90 and Cr. palmelloides, like other
      pyrenoid-less algae (lichen photobionts) reported previously, seem to lack the
      CCM. The present study is the first demonstration of the CCM in pyrenoid-less
      algae, indicating that pyrenoids or accumulation of Rubisco in the chloroplasts
      are not always essential for the CCM in algae. Focusing on this type of CCM in
      pyrenoid-less algae, the physiological and evolutionary significance of pyrenoid
      absence is discussed.

PMID- 9530872
TI  - Expression of NADH-dependent glutamate synthase protein in the epidermis and
      exodermis of rice roots in response to the supply of ammonium ions.
AB  - The mRNA and protein for NADH-dependent glutamate synthase (NADH-GOGAT; EC
      1.4.1.14) in root tips of rice (Oryza sativa L. cv. Sasanishiki) plants increases
      dramatically within 12 h of supplying a low concentration (> 0.05 mM) of ammonium
      ions (T. Yamaya et al., 1995, Plant Cell Physiol 36: 1197-1204). To identify the
      specific cells which are responsible for this rapid increase, the cellular
      localization of NADH-GOGAT protein was investigated immunocytologically with an
      affinity-purified anti-NADH-GOGAT immunoglobulin G. When root tips (> 1 mm) of
      rice seedlings which had been grown for 26 d in water were immuno-stained,
      signals for the NADH-GOGAT protein were detected in the central cylinder, in the
      apical meristem, and in the primordia of the secondary roots, Signals for
      ferredoxin-dependent GOGAT (Fd-GOGAT; EC 1.4.7.1) protein were also seen in the
      same three areas. When the roots were supplied with 1 mM ammonium ions for 24 h,
      there were strong signals for the NADH-GOGAT protein in two cell layers of the
      root surface, i.e. epidermis and exodermis, in addition to the cells giving
      signals in the absence of ammonium ions. The supply of ammonium ions was less
      effective on the profile of signals for Fd-GOGAT. Although the supply of ammonium
      ions had less effect on the expression of cytosolic glutamine synthetase (GS; EC
      6.3.1.2), this enzyme was also found to be located in the epidermis and
      exodermis, as well as in the central cylinder and cortex. The results indicate
      that NADH-GOGAT, coupled to the cytosolic GS reaction, is probably important for
      the assimilation of ammonium ions in the two cell layers of the root surface.

PMID- 9530873
TI  - Two jasmonate-inducible myrosinase-binding proteins from Brassica napus L.
      seedlings with homology to jacalin.
AB  - Two homologous but different cDNAs encoding a 97-kDa and a 70-kDa protein from
      Brassica napus L. seedlings have been characterized. Both proteins contain
      sequence motifs with high homology to the IgA binding lectin, jacalin, and the
      deduced 97-kDa protein contains the peptide sequences of myrosinase-binding
      protein. The 70-kDa and the 97-kDa protein can both be isolated as a complex
      containing myrosinase, indicating they indeed are myrosinase-binding proteins. We
      provide evidence that the 70-kDa protein binds IgA in vitro, and therefore
      classify the protein as a jacalin-type lectin. Both the 97-kDa and the 70-kDa
      proteins are encoded by a small number of genes in the Brassica genome. The mRNA
      for the 97-kDa protein is detected in both light- and dark-grown seedlings,
      whereas the mRNA for the 70-kDa protein is mainly detected in etiolated
      seedlings. The transcript levels for both proteins are transient and are rapidly
      increased by methyl jasmonate. The 70-kDa protein is synthesized de novo during
      germination and accumulates mainly in the hypocotyl and in the root. By
      immunogold labeling we show that a few cells scattered in the cotyledons of young
      seedlings (approx. 5% of total cells), contain protein-body-like structures with
      the 70-kDa protein. These bodies are present in a 10,000 g pellet from which the
      70-kDa protein can be extracted by sodium carbonate. In addition, the 70-kDa
      protein is detected in the amorphous structures of the vacuole in a few cells of
      the cotyledon, the hypocotyl and the root.

PMID- 9530874
TI  - Light-dependent fragmentation of the large subunit of ribulose-1,5-bisphosphate
      carboxylase/oxygenase in chloroplasts isolated from wheat leaves.
AB  - The large subunit (LSU) of ribulose-1,5-bisphosphate carboxylase/oxygenase
      (Rubisco; EC 4.1.1.39) is degraded into an N-terminal side fragment of 37 kDa and
      a C-terminal side fragment of 16 kDa by the hydroxyl radical in the lysates of
      chloroplasts in light (H. Ishida et al. 1997, Plant Cell Physiol 38: 471-479). In
      the present study, we demonstrate that this fragmentation of the LSU also occurs
      in the same manner in intact chloroplasts, and discuss the mechanisms of the
      fragmentation. The fragmentation of the LSU was observed when intact chloroplasts
      from wheat leaves were incubated under illumination in the presence of KCN or
      NaN3, which is a potent inhibitor of active oxygenscavenging enzyme(s). The
      properties, such as molecular masses and cross-reactivities against the site
      specific anti-LSU antibodies, of the fragments found in the chloroplasts were the
      same as those found in the lysates. These results indicate that, as in the
      lysates, the fragmentation of the LSU in the intact chloroplasts was also caused
      by the hydroxyl radical generated in light. The fragmentation of the LSU was
      completely inhibited by 3-(3',4'-dichlorophenyl)-1,1-dimethylurea (DCMU), and
      only partially inhibited by methyl viologen in the lysates. The addition of
      hydrogen peroxide to the lysates stimulated LSU fragmentation in light, but did
      not induce any fragmentation in darkness. Thus, we conclude that both production
      of hydrogen peroxide and generation of the reducing power at thylakoid membranes
      in light are essential requirements for fragmentation of the LSU.

PMID- 9530875
TI  - Presence of polymerized and free forms of the non-toxic type 2 ribosome
      inactivating protein ebulin and a structurally related new homodimeric lectin in
      fruits of Sambucus ebulus L.
AB  - Mature leaves of dwarf elder (Sambucus ebulus L.) contain the non-toxic type 2
      ribosome-inactivating protein ebulin 1 (Girbes et al., 1993b, J. Biol. Chem. 268:
      18195-18199). We have now found that the green fruits of dwarf elder contain both
      free and polymerized forms of ebulin (ebulin f) and a new homodimeric D-galactose
      binding lectin (SELfd). Polymerized material containing ebulin and lectin is
      composed of aggregates of variable relative molecular mass, some of them being
      close to 250,000. These aggregate forms are maintained in part by reducible
      disulphide bridges and reconstitute from reductant-free dialyzed material
      previously reduced with 2-mercaptoethanol. Direct incubation of free ebulin f
      with the free SELfd did not lead to polymerization, thus indicating that
      polymerization triggers some kind of substantial and perhaps catalyzed change in
      the structure of these proteins. Ebulin-containing polymerized material reacts
      with anti-ebulin f antibodies. Our results indicate that ebulin f is a fruit-form
      of ebulin 1. In contrast to green fruits, mature fruits lack both polymerized
      material and ebulin f, thus indicating some kind of reserve role for them in
      green fruits. Polymerization of ebulin and the dimeric lectin may represent a
      novel means of storing the non-toxic type 2 ribosome-inactivating proteins and
      lectins found in highly metabolic tissues, such as green fruits.

PMID- 9530876
TI  - Subcellular localization of beta-1,3-glucanase in Puccinia recondita f.sp.
      tritici-infected wheat leaves.
AB  - An antiserum raised against the purified 33-kDa beta-1,3-glucanase of wheat
      (Triticum aestivum L.) was employed to investigate the ultrastructural
      localization of the enzyme in wheat leaves infected with Puccinia recondita Rob.
      ex Desm. f.sp. tritici Eriks. and Henn. using a post-embedding immunogold
      labelling technique. In both compatible and incompatible interactions, beta-1,3
      glucanase was detected in the host plasmalemma and in the domain of the host cell
      wall near the plasmalemma of the mesophyll cells, but higher concentrations of
      the enzyme were detected in infected resistant wheat leaves than in infected
      susceptible ones. beta-1,3-Glucanase was also found in the secondary thickening
      of xylem vessels and in the walls of guard cells, epidermal cells and phloem
      elements, while no labelling was observed in host organelles, viz. vacuoles,
      mitochondria, endoplasmic reticulum, Golgi bodies, nuclei and chloroplasts. A low
      concentration of the enzyme was detected on the intercellular hyphal wall and in
      the hyphal cytoplasm. In the compatible interaction, beta-1,3-glucanase was
      demonstrated to accumulate predominantly in the haustorial wall and
      extrahaustorial matrix. In the incompatible interaction, strong labelling for
      beta-1,3-glucanase was found in host cell wall appositions, in the extracellular
      matrix in the intercellular space, and in electron-dense structures of host
      origin which occurred in the incompatible interaction only.

PMID- 9530877
TI  - Tonoplast intrinsic proteins from cauliflower (Brassica oleracea L. var.
      botrytis): immunological analysis, cDNA cloning and evidence for expression in
      meristematic tissues.
AB  - The vacuolar membrane (tonoplast) of plant cells contains aquaporins, protein
      channels that facilitate the selective transport of water. These tonoplast
      intrinsic proteins (TIPs) of 23-29 kDa belong to the ancient major intrinsic
      protein (MIP) family. A monospecific polyclonal antiserum directed against a 26
      kDa intrinsic protein from the tonoplast of meristematic cells from cauliflower
      (Brassica oleracea L. var. botrytis) was used to screen a cDNA library. Two
      distinct cDNAs have been isolated. Both clones, c26-1 and c26-2, encode closely
      related TIPs. The c26-1 insert, consisting of 933 bp upstream of the poly(A)
      tail, is a full-length cDNA with an open reading frame encoding a protein of 251
      amino acids with a calculated M(r) of 25,500. The c26-2 insert is a 5' truncated
      cDNA. The two cDNAs share 90.5% sequence identity within their overlapping coding
      regions but only 35% sequence identity in the 3' untranslated regions, indicating
      that highly related TIP-encoding genes are expressed in meristematic cells.
      Although TIPs have previously been found in a variety of cell types, they have
      not been found in meristems. The derived amino acid sequences (BobTIP26-1 and
      BobTIP26-2, respectively) closely resemble the aquaporin gamma-TIP from
      Arabidopsis thaliana. Northern blot analysis and in situ hybridization show that
      BobTIP26 mRNAs preferentially accumulate in highly meristematic cells, mostly
      before and during cell enlargement, and in the living cells of the xylem. This
      differential pattern of expression is also found by immunodetection of BobTIP26
      polypeptides. The gene expression patterns are discussed with respect to the
      probable function of the gene products.

PMID- 9530878
TI  - Arabidopsis SKP1, a homologue of a cell cycle regulator gene, is predominantly
      expressed in meristematic cells.
AB  - The yeast SKP1 gene and its human homolog p19skp1 encode a kinetochore protein
      required for cell cycle progression at both the DNA synthesis and mitosis phases
      of the cell cycle. In orchids we identified a cDNA (O 108) that is expressed in
      early stages of ovule development and is homologous to the yeast SKP1. Based on
      the orchid O 108 cDNA clone, we identified and characterized an Arabidopsis
      thaliana (L.) Heynh. cDNA designated ATskp1 that also has high sequence
      similarity to yeast SKP1. The Arabidopsis ATskp1 is a single-copy gene that
      mapped to chromosome 1. The expression of the ATskp1 gene was highly correlated
      with meristem activity in that its mRNA accumulated in all of the plant meristems
      including the vegetative shoot meristem, inflorescence and floral meristems, root
      meristem, and in the leaf and floral organ primordia. In addition, ATskp1 was
      also highly expressed in the dividing cells of the developing embryo, and in
      other cells that become multinucleate or undergo endoreplication events such as
      the endosperm free nuclei, the tapetum and the endothelium. Based on its spatial
      pattern of expression, ATskp1 is a marker for cells undergoing division and may
      be required for meristem activity.

PMID- 9530879
TI  - The plasma-membrane H(+)-ATPase from beet root is inhibited by a calcium
      dependent phosphorylation.
AB  - Several plasma-membrane proteins from beet root (Beta vulgaris L.) have been
      functionally incorporated into reconstituted proteoliposomes. These showed H(+)
      ATPase activity, measured both as ATP hydrolysis and H+ transport. The proton
      transport specific activity was 10 times higher than in plasma membranes, and was
      greatly stimulated by potassium and valinomycin. These proteoliposomes also
      showed calcium-regulated protein kinase activity. This kinase activity is
      probably due to a calmodulin-like domain protein kinase (CDPK), since two protein
      bands were recognized by antibodies against soybean and Arabidopsis CDPK. This
      kinase phosphorylated histone and syntide-2 in a Ca(2+)-dependent manner. Among
      the plasma-membrane proteins phosphorylated by this kinase, was the H(+)-ATPase.
      When the H(+)-ATPase was either prephosphorylated or assayed in the presence of
      Ca2+, both the ATP-hydrolysis and the proton-transport activities were slower.
      This inhibition was reversed by an alkaline-phosphatase treatment. A trypsin
      treatment (that has been reported to remove the C-terminal autoinhibitory domain
      from the H(+)-ATPase) also reversed the inhibition caused by phosphorylation.
      These results indicate that a Ca(2+)-dependent phosphorylation, probably caused
      by a CDPK, inhibits the H(+)-ATPase activities. The substrate of this regulatory
      phosphorylation could be the H(+)-ATPase itself, or a different protein
      influencing the ATPase activities.

PMID- 9530880
TI  - Compensation of decreased triose phosphate/phosphate translocator activity by
      accelerated starch turnover and glucose transport in transgenic tobacco.
AB  - Tobacco (Nicotiana tabacum L.) plants were transformed with an antisense
      construct of the chloroplast triose phosphate/phosphate translocator (TPT). Three
      transformant lines of the T4 progeny, which showed a large decrease in the
      transcript level of the TPT were used for further biochemical and physiological
      characterisation. In all antisense lines tested, TPT transport activity was
      diminished by 50-70% compared with the wild type (WT). Despite this high
      reduction in the transport capacity, alpha TPT plants lacked any visible
      phenotype. Hexokinase and alpha-amylase activities were increased in alpha TPT
      plants compared with the WT, whereas activities of ribulose-1,5-bisphosphate
      carboxylase/oxygenase and ADP-glucose pyrophosphorylase (AGPase) were not
      affected. At the end of a 14-h light period, leaf starch contents in alpha TPT
      lines were similar to those of the WT and controls, indicating that a decrease in
      the TPT had no effect on starch accumulation. Sucrose contents were diminished by
      more than 50% in alpha TPT lines compared with control plants. The time course of
      starch accumulation revealed a transient increase in the starch content in a
      selected alpha TPT line after 6 h in the light, followed by a decrease towards
      the end of the light period. Labelling with 14C indicated that during the dark
      and light (late afternoon) periods starch is mobilised at higher rates in alpha
      TPT lines than in the controls. Glucose/fructose ratios at the end of the dark
      period were increased from 1.2 in control plants to 2 in alpha TPT lines
      indicating increased amylolytic starch degradation. Initial rates of [14C]
      glucose transport in isolated chloroplasts were increased by a factor of 2-3 in
      alpha TPT plants compared with the WT. Rates of CO2 assimilation were
      substantially diminished in the alpha TPT lines in high CO2 and low O2, but
      remained unaffected in ambient CO2. The rate of photosynthetic electron transport
      during the induction of photosynthesis in saturating CO2 exhibited pronounced
      oscillations only in WT and control plants. Oscillations were less pronounced in
      alpha TPT plants, indicating that phosphate limitation of photosynthesis is
      lowered in alpha TPT plants compared with the WT. It is proposed that
      photoassimilates are more readily directed into starch biosynthesis in alpha TPT
      plants. This is supported by determinations of 3-phosphoglycerate levels (an
      activator of AGPase) during the transition from dark to light in high CO2.

PMID- 9530882
TI  - Association of nickel versus transport of cadmium and calcium in tonoplast
      vesicles of oat roots.
AB  - The plant vacuole has long been suspected of being a site for accumulation of Ni
      in plant roots, but testing this hypothesis directly by vacuole isolation is
      technically difficult and has not been reported. Here, we have attempted to
      determine if Ni can be transported into isolated oat (Avena sativa L.) root
      tonoplast vesicles as an alternative approach toward understanding the importance
      of the vacuole in Ni accumulation in roots. We found that, in contrast to Ca and
      Cd, Ni did not affect the proton gradient of vesicles (MgATP energized or
      artificially created), and further, that Cd/H antiport activity was not affected
      by the presence of Ni. Nickel was associated with vesicles, but relative rates of
      accumulation/association of metals with vesicles were Ca > Cd >> Ni.
      Protonophores and the potential Ni ligands citrate and histidine, and nucleoside
      triphosphates or PPi did not stimulate Ni association with vesicles. Comparison
      of Ni versus Ca and Cd associated with vesicles using various membrane
      perturbants indicated that while Ca and Cd are rapidly and principally antiported
      to the vesicle sap, Ni is only slowly associated with the membrane in a not
      easily dissociated condition. Our results indicate the absence of an Ni/H
      antiport or Ni-nucleotide-dependent pump in oat root tonoplasts, and support the
      contention that the vacuole is not a major compartment for Ni accumulation in oat
      roots.

PMID- 9530881
TI  - Purification and characterization of lanatoside 15'-O-acetylesterase from
      Digitalis lanata Ehrh.
AB  - Lanatoside 15'-O-acetylesterase (LAE) from in-vitro-cultivated cells of Digitalis
      lanata Ehrh. was isolated and partially sequenced. The enzyme was extracted with
      citrate buffer from acetone dry powder. It was purified in a two-step
      chromatographical procedure including Phenyl Sepharose hydrophobic interaction
      chromatography followed by CM Sepharose cation-exchange chromatography to more
      than 330 mumol.s-1.(g protein)-1. Sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis (SDS-PAGE) of the purified protein showed a major band at 39 kDa.
      The protein was identified by correlation of band intensity on SDS-PAGE and
      enzyme activity of CM Sepharose column fractions. Size-exclusion chromatography
      on Sephacryl 200 revealed a single activity peak with an apparent molecular mass
      of about 85 kDa. Electrophoresis under nondenaturating conditions of purified LAE
      showed only one band with esterase activity. The intensity of this band was
      correlated with that of the 39-kDa band after SDS-PAGE. About 30% of the protein,
      including the N-terminus and several fragments obtained by Lys-C protease
      digestion, was sequenced. A fragment obtained by Lys-C digestion showed partial
      homology to other hydrolases and apoplasmic proteins. It included the probable
      location of an active-site histidine. The activity of LAE was high in non
      morphogenic D. lanata cell strains selected for high activities in the chemical
      transformation of cardenolides, but rather low in the proembryogenic masses of
      the embryogenic cell strain VIII. It increased during the development of somatic
      embryos. The LAE activity in leaves of D. lanata plants was in the range 4-24
      nmol.s-1.(g protein)-1.

PMID- 9530883
TI  - The breast cancer screening controversy: lessons to be learned.

PMID- 9530884
TI  - DNA content and other factors associated with ten-year survival after resection
      of pancreatic carcinoma.
AB  - BACKGROUND AND OBJECTIVES: The 5-year survival rates after resection of
      pancreatic carcinoma have recently increased and are predicted by tumor size, DNA
      content, and lymph node metastases at the time of resection. However, whether the
      10-year survival rates have also increased and are similarly predicted by these
      factors is not known. METHODS: The influence of preoperative imaging tests,
      alcohol consumption, cigarette smoking, K-ras mutations, anatomic location,
      details of surgical resection, pathologic findings, and tumor DNA content on
      survival was tested for 96 patients after a successful resection of a pancreatic
      carcinoma with 17 patients being followed for more than 5 years. RESULTS: The 5-
      and 10-year patient survival rates were 18% and 3%, respectively. Univariate and
      multivariable analyses showed that tumor DNA content, pathologic tumor size, and
      lymph node metastases were the strongest prognostic indicators for long-term
      patient survival, although the importance of tumor size may diminish 2 or more
      years after resection. Surprisingly, the 11 patients with diploid carcinomas > or
      = 4 cm had an estimated 10-year survival rate of 36%. CONCLUSION: These results
      show that the 10-year survival rate for pancreatic carcinoma remains very low,
      although the subset of patients with biologically favorable tumors has a
      prolonged survival and possible cure after resection.

PMID- 9530885
TI  - The number of lymph node metastases influences survival in esophageal cancer.
AB  - BACKGROUND AND OBJECTIVES: Lymph node involvement adversely affects the survival
      of patients with esophageal cancer. We retrospectively investigated whether the
      number of involved lymph nodes and the degree of lymph node dissection affect
      survival. PATIENTS AND METHODS: Eighty-eight patients underwent surgical
      resection and reconstruction for T -T3 thoracic esophageal squamous cell
      carcinoma. Patients were classified into three groups: group 1, 32 patients
      without lymph node involvement; group 2, 26 patients with 1 to 3 positive nodes;
      and group 3, 30 patients with > or = 4 involved lymph nodes. RESULTS: The 3-year
      and 5-year survival rates were 34.8% and 30.0% in group 1, 30.0% and 22.7% in
      group 2, and 14.8% and 0% in group 3, respectively. The mean survival time (MST)
      X +/- SD of the patients in group 3 (453.06+/-74.5 days) was significantly
      shorter than in group 1 (450.1+/-450.5, P = 0.0005) and group 2 (937.3+/-1317.9,
      P = 0.0295). For patients in groups 1 and 2, the MST for three-field lymph node
      dissection (1136.9+/-1476.4 days) was longer than for two-field lymph node
      dissection (1007.4+/-1476.4 days, P = 0.0355). However, in group 3, there was no
      survival advantage to three-field lymph node dissection. CONCLUSION: We conclude
      that the survival in patients with thoracic esophageal cancer involving four or
      more nodes, is poorer than in patients with lesser involvement. Three-field lymph
      node dissection does contribute to prolonged survival in patients with node
      negative disease or fewer than four positive nodes.

PMID- 9530886
TI  - Sarcomas near extremity joints in adults.
AB  - BACKGROUND AND OBJECTIVES: There are technical difficulties in resecting soft
      tissue sarcomas extending to or crossing a joint. The objective of this study was
      to determine the rate of amputation and local recurrence rate for these sarcomas
      and compare them with the respective rates for overall extremity sarcomas.
      METHODS: Retrospective review of 78 patients with sarcoma near a joint compared
      with 215 patients with extremity sarcomas accrued during the same period, 1977
      1994. Of these 78 patients, 64 were in the lower and 14 in the upper extremity.
      Most common histologic subtypes were malignant fibrous histiocytoma (15/78, 19%),
      synovial sarcoma (11/78, 14%), liposarcoma (11/78, 14%), and leiomyosarcoma
      (10/78, 13%). The surgical treatment consisted of local excision in 10 (13%),
      wide excision in 56 (72%), and amputation in 12 (15%). Adjuvant radiation was
      given to 26 patients. RESULTS: Local recurrence was noted in 20% (16/78)
      patients. The incidence of local recurrence in the surgery alone group (n = 52)
      was 15% (8/52) and in the surgery plus adjuvant radiation group (n = 26) it was
      31% (8/26); P = 0.11. Of the 16 patients with local recurrence, 9 (56%) required
      amputation. The 5-year and 10-year survival rates for the entire group of
      patients were 68% and 60% respectively. On multivariate analysis survival varied
      according to grade (P = 0.05) and tumor size (P = 0.02). CONCLUSIONS: Amputation
      was finally required in 27% (21/78) for local control of the disease. The local
      recurrence rate was 20%. These rates appear to be somewhat higher than those
      reported in our overall extremity sarcoma series and those in most modern series
      of overall extremity sarcomas, but the 5- and 10-year survival rates are similar
      to those of the latter.

PMID- 9530887
TI  - Atypical hyperplasia in the era of stereotactic core needle biopsy.
AB  - BACKGROUND AND OBJECTIVES: To characterize both atypical hyperplasia (AH) and the
      malignancies typically present at open surgical biopsy in women diagnosed with AH
      by stereotactic core needle biopsy (SCNB). METHODS: Patients with AH diagnosed by
      SCNB were advised to undergo surgical biopsy to rule out an associated
      malignancy. Mammography findings, pathology reports and follow-up data were
      analyzed. RESULTS: AH was identified by SCNB in 38 of 893 (4.3%) patients.
      Carcinoma was identified in 12 of 33 (36.4%) patients who went on to surgical
      biopsy. Ductal carcinoma in situ (DCIS) was present in 11 of the 12 patients with
      malignancy. There were no characteristic mammographic findings which would
      identify patients with carcinoma. CONCLUSIONS: When SCNB returns a diagnosis of
      AH there is a substantial risk of an associated malignancy in the breast. There
      appear to be no definitive criteria to distinguish which patients harbor a
      malignancy, and surgical biopsy should always serve as an adjunct diagnostic
      procedure.

PMID- 9530888
TI  - Squamous cell carcinoma of the vulva in the south of Israel: a study of 50 cases.
AB  - BACKGROUND AND OBJECTIVES: Vulvar carcinoma accounts for 4.9% of all female
      genital tract malignancies in the south of Israel. The most common histologic
      type is squamous cell carcinoma (82%). The purpose of this study was to
      investigate the clinical findings, treatment, and outcome of patients with vulvar
      squamous cell carcinoma in the south of Israel. METHODS: Data from the files of
      50 patients with vulvar squamous cell carcinoma who were managed at the Soroka
      Medical Center between January 1961 and December 1996 were evaluated. RESULTS:
      Mean age at diagnosis was 67.1 years. The most prevailing presenting symptoms
      were vulvar lump, ulcer, and itching. Mean patient delay in seeking medical help
      was 48.2 months. Clinical palpation as a test for detecting groin lymph node
      metastases had a sensitivity and specificity of 57.1% and 61.5%, respectively.
      The 5-year survival rate was 60.3% overall. By means of univariate analysis, a
      significant worsening in survival was demonstrated with advancing stage of
      disease (P < 0.001), tumor >4 cm (P < 0.001), and positivity of surgical margins
      (P < 0.0001). In a multivariate analysis (Cox proportional hazards model) in a
      group of 45 patients, stage of disease was the strongest and the only significant
      predictor of survival (P = 0.0098). CONCLUSIONS: Vulvar squamous cell carcinoma
      predominantly affects older women. Stage of disease, tumor size, and status of
      surgical margins are sensitive predictors of survival. The treatment of choice
      for most patients is surgery consisting of radical vulvectomy and bilateral groin
      lymphadenectomy.

PMID- 9530889
TI  - Adenoma with clear cell change of the large intestine.
AB  - BACKGROUND AND OBJECTIVES: Clear cell change of the large intestinal neoplasm is
      rare, and its character remains unclear. We report a case of the large intestinal
      adenoma with clear cell change with immunohistochemical and molecular studies to
      investigate whether the clear cell change is associated with a malignant
      progression of the adenoma. METHODS: We studied the histochemical and
      immunohistochemical staining characteristics of the tumor by staining with
      hematoxylin-eosin, periodic acid-Schiff, alcian blue, and by immunostaining using
      antibodies against carcinoembryonic antigen, epithelial membrane antigen, p53,
      and Ki-67. The c-K-ras codon 12 point mutations were analyzed using a
      nonradioactive restriction fragment length polymorphism technique. RESULTS: The
      tumor was composed of a typical tubular adenoma and a tubular adenoma with clear
      cytoplasm. The clear cytoplasm was negative by mucin stains.
      Immunohistochemically p53 was negative in both the components. Labeling index of
      Ki-67 showed no significant difference between the two components. No codon 12
      mutation of c-K-ras gene was observed in both the components. CONCLUSION: These
      findings suggest that the clear cell change of the tubular adenoma is not
      associated with a malignant progression in adenoma-carcinoma sequence involving c
      K-ras and p53.

PMID- 9530891
TI  - Intraoperative use of radiofrequency treatment allows an increase in the rate of
      curative liver resection.

PMID- 9530890
TI  - Metastatic spinal cord compression as initial presentation of follicular thyroid
      carcinoma.
AB  - Follicular thyroid carcinoma, initially presenting as spinal cord compression due
      to metastatic lesions, is a less reported event. We present two cases of well
      differentiated thyroid carcinoma that led to spinal cord compression. A thorough
      search of the literature revealed only five similar cases. We summarize the
      clinical characteristics of these cases, the therapeutic measures used, their
      outcome, and the prognosis.

PMID- 9530892
TI  - Prostatic aspiration cytology using lumbar puncture needle.

PMID- 9530893
TI  - Micrometastasis in colorectal carcinoma: a review.
AB  - Lymph node metastasis is the most important predictor of prognosis, after
      surgery, in colorectal carcinoma. The term "micrometastasis" has evolved from a
      morphological definition to one that is used with molecular-based techniques. We
      review the literature to evaluate the significance of detecting micrometastases
      in colorectal carcinoma, either by morphological or molecular techniques, and
      address technical difficulties encountered with both. Routine use of
      immunohistochemistry is not recommended as most studies show little change in
      staging or prognosis. Radioimmunoguided surgery may prove beneficial, but
      problems of false positives in benign diseases need to be addressed.
      Immunohistochemical detection of micrometastatic deposits in bone marrow
      aspirates holds the most promise for clinical practice. Molecular techniques are
      more sensitive than immunohistochemistry, but prognostic value needs to be
      determined. Molecular diagnostics can also determine genetic alterations and
      mutations that should improve our understanding of metastatic colon cancer and
      staging accuracy.

PMID- 9530895
TI  - Rapid diagnosis of tuberculosis in the UK.

PMID- 9530894
TI  - Biliary tree malignancies.
AB  - Radiation therapy is used as definitive treatment for unresectable bile duct
      tumors, or as adjuvant therapy after resection. External beam irradiation of 45
      50 Gy is generally given whenever feasible. Intraluminal brachy-therapy is a
      useful technique to deliver higher doses of radiation to the tumor while
      respecting the tolerance of the surrounding normal tissues. Brachytherapy can be
      given at a high dose rate or low dose rate via an in-dwelling biliary drainage
      catheter to boost external beam doses. Brachytherapy alone is reserved for
      palliative therapy. Techniques should be implemented with care to make them not
      only effective but safe. The long-term efficacy and morbidity of this mode of
      radiation should be studied further. Only large prospective trials can lead to
      resolution of some of the questions yet unsolved in treatment of these
      challenging malignancies.

PMID- 9530896
TI  - Heterosexual behaviour, risk factors and sexually transmitted infections among
      self-classified homosexual and bisexual men.
AB  - Our study of men presenting at a genitourinary medicine clinic shows that self
      classification into homosexual or bisexual does not accurately define behaviour.
      We found that 8.5% of self-defined homosexual men had had heterosexual
      intercourse in the past year and that 26% of self-defined bisexual men had not.
      Overall, 19% of homosexual/bisexual men reported vaginal intercourse in the past
      year and a further 42% in their lifetime. Compared with heterosexual men
      attending our clinic, the practising bisexual men were significantly more likely
      to come from a white ethnic group (P < 0.003) and to use condoms invariably with
      regular female partners (P = 0.0001). There was no significant difference in
      consent for HIV testing between homosexual (43%), practising bisexual (49%) and
      heterosexual (42%) men despite significantly different perceptions of risk. None
      of the practising bisexual men was seropositive for HIV infection (P = 0.06) or
      for syphilis (P = 0.02), or had chlamydial infection, which was found
      infrequently among homosexual men in general (P = 0.00001). HIV infection found
      in 19.4% of the exclusively homosexual men was associated with more frequent
      alcohol consumption (P=0.06).

PMID- 9530897
TI  - Rapid HIV testing with same-day results: a field trial in Uganda.
AB  - Rapid, on-site HIV testing with same-day results may improve services and
      increase the number of clients who learn their serostatus in developing
      countries. To validate test performance under field conditions and assess the
      change in the proportion of clients who learn their serostatus, we conducted a
      field trial using the Capillus HIV-1/HIV-2 assay (Cambridge Diagnostics) at the
      AIDS Information Centre counselling and testing sites in Uganda. Compared to the
      standard 2-EIA testing algorithm, the sensitivity of Capillus was 99.6% (95% CI;
      98.5%, 99.9%), the specificity was 98.8% (95% CI; 98.1%, 99.3%), the positive
      predictive value was 96.5% (95% CI; 94.5%, 97.8%), and the negative predictive
      value was 99.9% (95% CI; 99.5%, 100%). It took less than 5 min to perform a
      single test, and results were returned to clients in less than an hour, during
      which time clients were counselled. This resulted in a 27% increase in the
      proportion of clients who learned their serostatus and received counselling. We
      conclude that simple, rapid HIV tests can be performed accurately on-site within
      the time frame of a clinic visit, increasing the number of clients who learn
      their serostatus and receive post-test counselling.

PMID- 9530898
TI  - Gender-related correlates and predictors of consistent condom use among young
      adult African-American women: a prospective analysis.
AB  - The present study examined the correlates of consistent condom use among African
      American women and prospectively evaluated the stability of these significant
      variables to predict consistent condom use at 3-month follow-up. A sample of 128
      African-American women, 18-29 years of age completed a baseline interview and 3
      months later completed a similar follow-up interview (n = 100). Compared to women
      who were inconsistent condom users, women who were consistent condom users were
      more likely to: have high assertive communication skills (OR=13), desire not
      becoming pregnant (OR=8.6), have high sexual self-control over condom use
      (OR=7.6), perceive having control over their partners' use of condoms (OR=6.6),
      be younger (OR=5.8), and report having a partner that was not committed to the
      relationship (OR=3.3). Prospective analyses identified baseline level of condom
      use as the best predictor of condom use at 3-month follow-up. Women who were
      consistent condom users at baseline were 6.3 times as likely to be consistent
      condom users at 3-month follow-up. In conclusion, HIV prevention programmes for
      women need to be gender specific and need to be implemented before high-risk
      behaviours are established and may be more difficult to modify.

PMID- 9530899
TI  - Prevalence and risk of HIV infection among female sex workers in Burkina Faso.
AB  - Little information is available regarding human immunodeficiency virus (HIV)
      infection among female sex workers (FSW) in Burkina Faso, West Africa. A cross
      sectional study was conducted in Ouagadougou and Bobo-Dioulasso, the 2 largest
      cities of the country, to determine the prevalence of HIV infection and other
      sexually transmitted diseases (STDs) among FSWs, and to investigate the factors
      which were associated with HIV infection in this population. From October to
      November 1994, 426 FSWs were recruited. The method of anonymous and unlinked HIV
      screening recommended by the World Health Organization (WHO) was used. The
      overall HIV seroprevalence was 58.2% (95% confidence interval: 53.4-62.9) and
      52.6% of FSWs had at least one STD agent. The most common STDs were
      trichomoniasis (23%), syphilis (15%) and gonorrhoea (13%). In a logistic
      regression analysis, risk factors for HIV infection were high gravidity (> or = 2
      pregnancies), low perception of personal risk of HIV infection, syphilis and the
      presence of genital warts. These results suggest that FSWs in Burkina Faso need
      better information about HIV transmission and prevention and then need better
      access to STD detection and management services.

PMID- 9530900
TI  - Risk factors for concordant HIV infection in heterosexual couples in Trinidad.
AB  - Risk factors for HIV infection in partners of HIV-seropositive index cases were
      investigated in a cross-sectional survey. Between September 1992 and April 1994 a
      total of 251 HIV-infected persons and 76 of their sexual partners were
      interviewed at the main sexually transmitted diseases (STDs) clinic in Trinidad.
      All participants gave signed consent and responded to a questionnaire. Sixty-four
      couples had risks for HIV infection through heterosexual intercourse only.
      However, many recruited sex partners (57/64) reported heterosexual intercourse
      with persons in addition to the index cases. Overall HIV concordance (both index
      case and partner HIV infected) was 45% in the couples. HIV concordance was not
      found to be related to the sexual practices within the studied unions nor to the
      clinical status of the index case. After allowing for confounding factors there
      was an increased risk for HIV concordance in couples in unions for > or = 1 year
      (adjusted OR 3.48; 95% CI 0.89-13.69, P = 0.055), and in those in which sex
      partners had a past history of genital sores (adjusted for prostitution: OR 4.50;
      95% CI 1.01-20.4). Interventions targeted at reducing high-risk sexual behaviour,
      prostitution and cocaine use could be beneficial in reducing the spread of STDs
      and HIV in Trinidad.

PMID- 9530901
TI  - Co-trimoxazole desensitization in HIV-seropositive patients.
AB  - Co-trimoxazole (trimethoprim-sulphamethoxazole) is an effective prophylactic
      agent against Pneumocystis carinii pneumonia (PCP). However, it is associated
      with a high frequency of adverse reactions in immunocompromised patients which
      may preclude its use. Fourteen patients with a definite history of adverse
      reactions to co-trimoxazole on standard PCP prophylactic dosage were selected for
      desensitization using a regimen of gradual incremental exposure over an 11-day
      period. Eight (57.1%) were successfully desensitized and have continued on oral
      co-trimoxazole at maximum 21 months' follow-up. This report demonstrates that
      oral desensitization as an outpatient procedure is an effective and safe option
      for both primary and secondary PCP prophylaxis in HIV-seropositive patients with
      previous adverse drug reactions.

PMID- 9530902
TI  - Liaison between gynaecologists, microbiologists and genitourinary medicine
      clinics in the management of patients with genital chlamydia and gonococcal
      infections.
AB  - Inadequate treatment and follow-up of women with genital infection with Chlamydia
      trachomatis and Neisseria gonorrhoeae can cause long-term morbidity. Inadequate
      contact tracing can predispose to re-infection. As some women with genital
      infections present to agencies other than genitourinary medicine (GUM) clinics,
      improved liaison between these and GUM departments are important in safeguarding
      proper follow-up and contact tracing.

PMID- 9530903
TI  - Collaborative approach to improve the detection and management of trichomoniasis
      in a low prevalence district.
AB  - We describe a simple collaborative approach developed by the departments of
      cytology, microbiology and genitourinary (GU) medicine for the detection,
      diagnosis and management of microbiologically confirmed Trichomonas vaginalis
      (TV) infection. Over a 2-year period, 54 (0.1%) of 52,440 cervical smears were
      reported to show TV, but microbiological confirmation was made in only 76% of 34
      patients from whom a vaginal swab was subsequently taken. Trichomoniasis should
      not be diagnosed by cytology alone and clinicians need further education on the
      role of cytology in diagnosing sexually transmitted diseases (STDs). Over the
      same period, from a total of 96 cases of TV identified in the district, only 12
      (13%) were first diagnosed in the department of GU medicine. Forty per cent of
      the other 84 patients were subsequently seen in the GU clinic for test of cure,
      contact tracing and screening for other STDs. Collaborations between departments
      may improve the management of trichomoniasis and other conditions in the
      community and their development should be encouraged.

PMID- 9530904
TI  - Perceptions and acceptability of the female condom [Femidom] amongst commercial
      sex workers in the Songkla province, Thailand.
AB  - In a prospective descriptive study on the perceptions and acceptability of the
      female condom in a group of Thai commercial sex workers (CSWs) in the Songkla
      province, we invited CSWs from selected brothels to participate. Those who used
      the female condom were interviewed after one week and 16 weeks of use. Focus
      group discussions were also conducted at the end of the study period to obtain
      additional information. The group comprised 56 CSWs. Only 34% of them had heard
      of the female condom prior to this study and none had ever used one. A high
      proportion of CSWs reported positive experiences and perceptions. There were no
      significant changes in perceptions and experiences during the study. Eighty per
      cent of participants said they were satisfied with the female condom and would
      use it again in the future and would recommend it to their friends. However, the
      female condom was used in only 29% of the total number of sexual acts reported,
      and 98% of CSWs said they would prefer to use a male condom for sex work. Many of
      the women were concerned that the physical appearance of the condom would reduce
      its acceptability to their clients. This was the most frequently cited reason for
      not using the female condom in the future. While a promising device, the female
      condom must also become more acceptable to men if it is to enable women to be in
      control of their own protection from pregnancy and STD/HIV.

PMID- 9530905
TI  - Evaluation of an HIV saliva test for the detection of HIV-1 and HIV-2 antibodies
      in high-risk populations in Abidjan, Cote d'Ivoire.
AB  - To evaluate saliva testing in a West African field situation where both HIV-1 and
      HIV-2 are present, a cross-sectional study was conducted among female sex workers
      (FSWs) and their stable male partners (SMPs) at a STD/HIV clinic in Abidjan, Cote
      d'Ivoire. Saliva samples were collected with the Omni-SAL device and tested for
      antibodies to HIV-1 or HIV-2 by GACELISA. The HIV seroprevalence was 71% among
      468 FSWs and 61% among 31 SMPs. Salivary HIV antibodies were detected in all 227
      HIV-1-seropositive, in all 6 HIV-2-seropositive and in 115 of 117 dually
      seroreactive participants, while no salivary HIV antibodies were detected in 148
      of 149 seronegative participants. The sensitivity and specificity of the saliva
      test were 99.4% and 99.3% respectively, and the positive and negative predictive
      values were 99.7% and 98.7% respectively. In this West African field situation
      saliva testing has a high validity compared to serum testing. The Omni-SAL and
      GACELISA combination is an alternative strategy to serological testing because of
      its high sensitivity and specificity, the ease and safety of sample collection
      and its relatively low cost.

PMID- 9530906
TI  - Koro presenting to genitourinary medicine services.

PMID- 9530907
TI  - An audit of the use of prophylaxis against toxoplasmic encephalitis in HIV
      disease.

PMID- 9530908
TI  - Genitourinary medicine in the next millennium. Report on the conference held on
      19 September 1997 at the Royal College of Physicians of London.

PMID- 9530909
TI  - Cerebral abscesses in a patient with AIDS caused by methicillin-resistant
      Staphylococcus aureus.

PMID- 9530910
TI  - HIV/AIDS in a Brazilian prison.

PMID- 9530911
TI  - Are the Health of the Nation's targets attainable?

PMID- 9530912
TI  - The making, changing, and breaking of contacts.

PMID- 9530913
TI  - Mitochondria - the Kraken wakes!

PMID- 9530914
TI  - Synaptic metaplasticity and the local charge effect in postsynaptic densities.
AB  - Synaptic plasticity might be one of the elementary processes that underlies
      higher brain functions, such as learning and memory. Intriguingly, the capacity
      of a synapse for plastic changes itself displays marked variation or plasticity.
      This higher-order plasticity, or metaplasticity, appears to depend on the same
      macromolecules as plasticity, most notably the NMDA receptor and Ca2+/calmodulin
      kinase II; yet we do not understand metaplasticity in molecular terms.
      Metaplasticity has a feedback-inhibition character that confers stability to
      synaptic patterns, whereas in plasticity, the molecular events implicated tend to
      have an opposite effect. As a resolution to this difference, we suggest that
      metaplasticity be considered in a biophysical context. It has been shown that
      autophosphorylation of Ca2+/calmodulin kinase II in postsynaptic densities
      generates changes in the local electrostatic potential sufficient to affect the
      direction of synaptic plasticity. We propose that this finding could help explain
      both the puzzling abundance of Ca2+/calmodulin kinase II in the postsynaptic
      density and the metaplasticity of synaptic transmission.

PMID- 9530916
TI  - A novel signaling system from the synapse to the nucleus.

PMID- 9530915
TI  - Psychiatric genetics: search for phenotypes.
AB  - Failure to obtain convincing results in psychiatric genetics can partly be
      attributed to the fact that progress in molecular biology and genetic
      epidemiology has not been followed by an equivalent development in phenotypic
      description. Instead of relying entirely on classical nosological approaches, we
      argue that identifying more homogeneous forms of diseases through a'candidate
      symptom approach' among affected subjects and an endophenotype approach that
      identifies sub-clinical traits among non-affected relatives might yield better
      results. Examples where these strategies have already been fruitful when applied
      to complex diseases are presented in this review. Focusing on vulnerability
      traits might stimulate the redefinition of traditional psychiatric syndromes and
      help to bridge the gap between clinical and experimental approaches.

PMID- 9530917
TI  - Strategies utilized by migrating neurons of the postnatal vertebrate forebrain.
AB  - Structural brain repair has become a possibility with the identification and
      characterization of persistent neuronal progenitor cells in both the neonatal and
      adult brain. However, despite recent advances in the identification, propagation
      and expansion of these cells, they will not be useful therapeutically until
      methods are available for directing or delivering them to sites of need. As a
      result, the natural history and induction of neuronal migration into adult brain
      tissue has assumed new importance in clinical neurobiology. In this review we
      consider the cellular and molecular bases of neuronal migration into the
      postnatal forebrain. In particular, we discuss two natural paradigms of postnatal
      neuronal recruitment: radial-cell-directed neuronal migration to the songbird
      neostriatum, and neurophilic migration to the rodent olfactory bulb. In each, we
      will focus on the dynamic interactions between the migrants, their cellular
      guides and the local environment, and the effect of those interactions on
      migrational success.

PMID- 9530918
TI  - CD95-CD95L: can the brain learn from the immune system?
AB  - Members of the tumor necrosis factor/nerve growth factor receptor superfamily of
      cell-surface molecules can play the dual role of mediating either cytotoxicity or
      cell survival, both in the immune system and in the nervous system. A member of
      this superfamily, CD95 (also known as ApoI or Fas), was initially identified in
      the immune system and has been shown to mediate receptor-dependent programmed
      cell death and to be expressed in the nervous system. In neurodegenerative
      disorders, CD95-CD95 ligand expression on glial cells might precede receptor
      mediated apoptosis by cells of the CNS. It is now being recognized that CD95
      signaling by immune cells mediates effects other than apoptosis, such as cell
      survival and under inflammatory conditions expression of this protein promotes
      neural-immune interactions. Both neuroscientists and immunologists can contribute
      to defining the mechanisms underlying these divergent effects and utilize such
      knowledge to aid understanding of cell death and survival.

PMID- 9530919
TI  - The macro- and microarchitectures of the ligand-binding domain of glutamate
      receptors.
AB  - Over the last decade, a large body of information regarding the amino acid
      sequences and tertiary structures of many proteins has accumulated. Subtle
      similarities in sequence patterns identified between glutamate receptors and
      bacterial periplasmic substrate-binding proteins have suggested that structural
      kinship exists between these protein families. Many of the bacterial periplasmic
      binding proteins but none of the glutamate receptors have been crystallized so
      far. The following article reviews how the resemblance between these two protein
      families led to computer-assisted structural models of crucial elements involved
      in ligand binding by various glutamate receptors. A plausible dynamic model of
      the molecular mechanism of activation and desensitization of glutamate-receptor
      channels is also discussed.

PMID- 9530920
TI  - New perspectives on the function of myelin galactolipids.
AB  - A defining feature of the vertebrate nervous system is the ensheathment of axons
      by myelin, a multilamellar membrane containing a small group of proteins and an
      abundance of the galactolipid galactocerebroside (GalC) and its sulfated
      derivative sulfatide. Several in vitro studies have suggested that these
      galactolipids transduce developmental signals, facilitate protein trafficking and
      stabilize membranes. In addition, mice lacking the ability to synthesize GalC or
      sulfatide form dysfunctional and unstable myelin. These findings suggest that the
      galactolipids are essential components of myelin, and that functional and
      structural properties of myelin result from the combined contributions of
      galactolipids and proteins.

PMID- 9530921
TI  - Is there a correlation between scores of nociceptive behavioral responses to
      formalin injections given at different body sites in the rat?
AB  - Correlations between behavioural nociceptive responses to an injection of
      formalin solution in the hindpaw and upper lip were sought in 28 male rats
      divided into two groups. One group received a first injection in the hindpaw and
      7 days later, a second one in the lip (paw-lip group). The injection order was
      reversed in the second group (lip-paw group). After each injection, the duration
      of lip rubbing for the orofacial formalin test, the duration of paw licking and
      the number of paw flinchings for the hindpaw test were measured. The Spearman
      test revealed no correlation between lip rubbing and paw flinching in either
      group but a significant correlation between lip rubbing and paw licking occurred
      in both groups.

PMID- 9530922
TI  - Identification of a sex steroid-inducible gene in the neonatal rat hypothalamus.
AB  - By the cDNA subtraction between cDNA preparations from androgenized and intact
      neonate rats hypothalami, granulin/ epithelin (grn) gene was identified as a gene
      enriched by androgenization. Strong grn mRNA signals were detected by in situ
      hybridization in the ventromedial nucleus (VMH) and the arcuate nucleus (ARC) of
      the hypothalamus of a 5-day-old male. The grn gene expression level in the
      hypothalamus was similar between males and females at birth. At 10 days of age,
      this level was maintained in males, but decreased to 1/4 in females. Thus, grn
      can be the gene of which expression in the VMH and ARC is sustained by endogenous
      androgen in male neonates.

PMID- 9530923
TI  - Glutamate induces hydroxyl radical formation in vivo via activation of nitric
      oxide synthase in Sprague-Dawley rats.
AB  - It was recently reported that neuronal nitric oxide synthase (NOS) generates
      oxygen-derived free radicals in vitro at low concentrations of L-arginine. Using
      the microdialysis technique, we monitored both hydroxyl radical (.OH) and nitric
      oxide (.NO) formation in rat striatum perfused with glutamate (500 mM). .OH and
      .NO were quantitated in microdialysates by measuring the amounts of the non
      enzymatic hydroxylation product of salicylate (2,3-dihydroxybenzoic acid) and the
      metabolites of .NO (nitrite + nitrate), respectively. .OH levels were
      dramatically increased during glutamate perfusion, while .NO generation was
      virtually abolished. .OH production was inhibited by the specific NOS blocker, NG
      nitro-L-arginine methyl ester. This effect was not reversed but potentiated by L
      arginine. Thus, it is likely that NOS generates oxygen-derived free radicals
      instead of .NO in brain subjected to highly excitotoxic conditions.

PMID- 9530924
TI  - Multi-joint coordination strategies for straightening up movement in humans.
AB  - Complex movement execution theoretically involves numerous biomechanical degrees
      of freedom, leading to the concept of redundancy. The kinematics and kinetics of
      rapid straightening up movement from the squatting position were analysed with
      the optoelectronic ELITE system in 14 subjects. We found multiple acceleration
      and deceleration peaks for the hip, knee and ankle joints during the early
      extension phase of the movement. In order to test the temporal coordination
      between the angular acceleration of these joints, conjugate crosscorrelation
      functions (CCF) between each set of two variables were calculated. We found a
      bimodal distribution of the maximum CCF in positive and negative values
      suggesting the existence of two distinct strategies, the in-phase and the out-of
      phase strategy for each pair of joints. The hip and knee coordination strategies
      (in- or out-of-phase) were well conserved in each subject for repetitive
      movements. Combination of joint pair strategies was more reproducible for the hip
      knee/knee-ankle pair than for the other combinations, suggesting that the
      straightening up strategies are organised around the knee. We conclude that
      mastering of the redundancy problem can be realised by using coordination
      strategies characterised by opposed joint acceleration patterns.

PMID- 9530925
TI  - Task-related variations in motoneuronal drive to a human intrinsic hand muscle.
AB  - Maximal electromyogram (EMG) levels of the first dorsal interosseus muscle (FDI)
      were studied during maximal pinching between index finger and thumb at two
      different wrist angles. Despite the fact that there was no change in the
      biomechanical conditions for the FDI, the maximal EMG levels of the FDI differed
      significantly; typically EMG levels were higher while pinching at a maximally
      flexed wrist angle compared to a maximally extended wrist angle. The stability of
      the EMG recordings was checked with supramaximal peripheral nerve stimulation.
      Significant changes in the area of the compound muscle actions potentials (M
      waves) were obtained. However, these changes could not explain the observed
      differences in the maximal EMG levels. Our results suggest that the ease of
      producing a maximal drive to the FDI muscle depends on the motor task.

PMID- 9530926
TI  - Kappa-B like DNA-binding activity is enhanced after spaced training that induces
      long-term memory in the crab Chasmagnathus.
AB  - Regulation of gene expression has been involved in long-term memory
      consolidation. Present results support the role of Rel/ NFkappa-B like activation
      in this process. In the crab Chasmagnathus, the spaced presentation of 15 or more
      danger stimuli induces long-term habituation (LTH), while no LTH is observed
      after a massed training of 600 trials. When a group trained with 30 spaced trials
      was compared with a passive control group and massed trained groups, a higher
      level of specific Rel/kappa-B like DNA-binding activity was found in brain
      nuclear extracts. These results strongly suggest that the enhancement of
      Rel/kappa-B like DNA-binding activity in the brain is specifically related to LTH
      formation.

PMID- 9530927
TI  - Experimental acute pancreatitis results in increased blood-brain barrier
      permeability in the rat: a potential role for tumor necrosis factor and
      interleukin 6.
AB  - Pancreatic encephalopathy is a severe complication of acute pancreatitis.
      Proinflammatory cytokines may play a role in the development of multi-organ
      failure during pancreatitis. In the present study, we measured the changes in the
      blood-brain barrier (BBB) permeability concomitantly with the determination of
      serum tumor necrosis factor (TNF) and interleukin-6 (IL-6) levels in rats before,
      as well as 6, 24 and 48 h after the beginning of intraductal taurocholic acid
      induced acute pancreatitis. Cytokine concentrations were measured in bioassays
      with specific cell lines (WEHI-164 for TNF and B-9 for IL-6), while the BBB
      permeability was determined for a small (sodium fluorescein, molecular weight
      (MW) 376 Da), and a large (Evans' blue-albumin, MW 67000 Da) tracer by
      spectrophotometry in the parietal cortex, hippocampus, striatum, cerebellum and
      medulla of rats. The serum TNF level was significantly (P < 0.05) increased 6 and
      24 h after the induction of pancreatitis, while the IL-6 level increased after 24
      and 48 h. A significant (P < 0.05) increase in BBB permeability for both tracers
      developed at 6 and 24 h in different brain regions of animals with acute
      pancreatitis. We conclude that cytokines, such as TNF and IL-6, may contribute to
      the vasogenic brain edema formation during acute pancreatitis.

PMID- 9530928
TI  - Sexually dimorphic MK801-induced c-fos in the rat hypothalamic paraventricular
      nucleus.
AB  - MK801 induces Fos-like immunoreactivity (FLI) in the paraventricular nucleus
      (PVN) in a sex, age, hormone and dosage dependent manner. MK801 (1.0 mg/kg)
      elicited greater behavioural disruption, but less FLI in the PVN of cycling and
      lactating female rats, compared to like-treated males. Results from
      gonadectomized rats with or without acute steroid replacement resembled those
      seen in intact rats but sex differences were extinguished. At a lower dose (0.1
      mg/kg), behavioural effects were diminished but females exhibited more
      behavioural disruption. At this dose however, more FLI was seen in the PVN of
      females compared to males, but only male-lactating female differences were
      significant. Taken together, the data suggest that the action of MK801 on the PVN
      is influenced by gonadal steroids.

PMID- 9530929
TI  - Characterization of Cyprinus carpio brain nitric oxide synthase.
AB  - Nitric oxide synthase (NOS) activity is found both in soluble and in particulate
      fractions of the carp brain. The Km values for arginine are 2.8+/-0.5 and 3.3+/
      0.4 microM for the soluble and particulate fractions, respectively. K for NG
      monomethyl-L-arginine inhibitor are 2.6+/-0.5 and 2.9+/-0.6 microM, and
      activation energy for the breakdown of the substrate-enzyme complex 8120+/-710
      and 4620+/-450 cal per mole. Carp enzyme shows higher affinity than rat NOS for
      Ca2+ and for the competitive inhibitor 7-nitroindazole.

PMID- 9530930
TI  - Mitogenic signaling from P1 and P2 purinergic receptors to mitogen-activated
      protein kinase in human fetal astrocyte cultures.
AB  - To investigate potential trophic actions of extracellular ATP in human
      astrocytes, we have examined mitogenic signaling by purinergic receptors in
      cultures prepared from first trimester rostral central nervous system tissue. We
      found that ATP and ATPgammaS, a hydrolysis-resistant analog, stimulated DNA
      synthesis, thereby indicating that P2 purinergic receptors can stimulate
      mitogenic signaling in these cells. In addition, ATP activated a mitogen
      activated protein kinase (MAPK) termed ERK (extracellular signal-regulated
      protein kinase), a key component of signal transduction pathways involved in
      cellular proliferation and differentiation. The activation of MAPK was mediated
      at least in part by P2 purinergic receptors, because a P2 purinoceptor
      antagonist, suramin, inhibited the ATP-evoked stimulation by 50%, whereas a P1
      purinergic-receptor antagonist, 8-(para-sulfonphenyl)-theophylline, was without
      effect. In contrast to rat astrocytes, adenosine/P1 purinergic-receptor agonists,
      2-chloroadenosine and 5'-N-ethylcarboxyamidoadenosine, stimulated MAPK activity
      and DNA synthesis in human astrocytes. A selective inhibitor of protein kinase C,
      Ro 31-8220, blocked the ability of ATP and adenosine analogs to stimulate MAPK,
      thereby indicating that protein kinase C is upstream of MAPK in both P2- and P1
      receptor signaling pathways. An inhibitor of the MAPK activator MEK, PD 098059,
      effectively blocked ATP- and 2-chloroadenosine-induced DNA synthesis, thereby
      indicating that the ERK/MAPK cascade mediates mitogenic signaling by P2 and P1
      purinergic receptors in human fetal astrocytes. These findings suggest a role for
      P1 and P2 purinergic receptors in the proliferation of human fetal astrocytes.

PMID- 9530931
TI  - Fenamates protect neurons against ischemic and excitotoxic injury in chick embryo
      retina.
AB  - Three fenamates (flufenamate, meclofenamate and mefenamate) were examined for
      their protective effect on neurons under ischemic (glucose/oxygen deprivation) or
      excitotoxic conditions, using the isolated retina of chick embryo as a model.
      Retinal damage was evaluated by histology and lactate dehydrogenase assay. Whole
      cell recording was used to examine the direct effect of the fenamates on
      glutamate receptor-mediated currents. The fenamates protected the retina against
      the ischemic or excitotoxic insult. Part of the neuroprotection by the fenamates
      derived from inhibition of N-methyl-D-aspartate receptor-mediated currents.
      However, kainate receptor-mediated currents were not blocked by the fenamates,
      which nonetheless reduced kainate receptor-mediated retinal damage. Our results
      raise the possibility that fenamates may serve as lead structures in the
      development of novel therapeutic agents against brain ischemia.

PMID- 9530932
TI  - Voltage gated Na+ channels contribute to membrane voltage fluctuation in alphaT3
      1 pituitary gonadotroph cells.
AB  - AlphaT3-1 cells showed a slope resistance of 1.8 Gomega. The cell membrane
      surface was not smooth and a scanning electron micrograph showed a complex
      structure with blebs and microvilli like projections. The cells showed
      spontaneous fluctuations at zero current resting membrane potential and
      hyperpolarization increased the amplitude of membrane potential fluctuations. The
      amplitude of membrane potential fluctuations at hyperpolarized membrane potential
      was attenuated on application of TTX to the bath solution. The potential at which
      half steady state inactivation of isolated sodium current occurred, was at a very
      hyperpolarized potential (-95.4 mV). The study presented in this paper shows that
      the voltage gated sodium channels contribute to the increase in the amplitude of
      electrical noise with hyperpolarization in alphaT3-1 cells.

PMID- 9530933
TI  - Differentiation-dependent expression of transgenes in engineered astrocyte cell
      lines.
AB  - The utility of transgenes for both basic and applied studies has been augmented
      by the recent advent of versions that can be regulated by the addition of
      suitable activators. However, still more convenient would be transgenes whose
      expression responded appropriately to endogenous signals. The promoter of the
      glial fibrillary acidic protein (GFAP) gene is a candidate for this role in the
      central nervous system (CNS) since the GFAP gene is specifically expressed in
      astrocytes in the CNS and its activity is upregulated in response to almost any
      CNS injury. As a feasibility study, we isolated a C6 rat glioma cell line stably
      transfected with a lacZ reporter gene driven by the gfa2 human GFAP promoter
      fragment. We find that the activity of the transgene indeed responds to an
      environmental signal, forskolin, that induces astrocyte-like differentiation of
      C6 cells. We also isolated a C6 line carrying a transgene in which the gfa2
      promoter directs expression of a cDNA for tyrosine hydroxylase (TH), the rate
      limiting enzyme for catecholamine synthesis. This transgene should be of
      considerable interest for gene therapy for Parkinson's disease. We show that in
      this cell line both TH mRNA and protein are upregulated by forskolin. Finally, we
      note that the growth rate of C6 cells is severely depressed by forskolin,
      suggesting that predifferentiation of these cells prior to implant may retard
      their tumor forming capacity, prolonging the time that they can be used in animal
      models in vivo.

PMID- 9530935
TI  - The cost of epilepsy care to the community.

PMID- 9530934
TI  - Response of rat adrenal neuropeptide Y and tyrosine hydroxylase mRNA to acute
      stress is enhanced by long-term voluntary exercise.
AB  - Neuropeptide Y (NPY) and catecholamines are synthesized in response to stress.
      Adrenal NPY mRNA and tyrosine hydroxylase (TH) mRNA were measured by Northern
      analysis 2 h after a single 20 min bout of shaker stress in exercised and
      sedentary male Sprague-Dawley rats. Long-term exercise (18 weeks of voluntary
      wheel running) alone did not significantly alter adrenal NPY mRNA or TH mRNA
      levels. However, increases in stress-induced NPY and TH mRNA abundances were
      significantly enhanced by long-term exercise (P < 0.01). These results suggest
      that long-term physical activity may enhance the ability to synthesize NPY and
      catecholamines under conditions of stress.

PMID- 9530936
TI  - Analysis of MMPI patterns in patients with psychogenic pseudoseizures.
AB  - We performed pattern analysis of the Minnesota Multiphasic Personality Inventory
      (MMPI) profiles of 55 patients with pseudoseizures in order to establish whether
      there was any single pattern which would be sufficient to characterize the entire
      sample. Two published methods of pattern analysis were used. Neither method
      revealed a single pattern or profile code which could best characterize the
      sample. The Graham method revealed that the Hysteria and Schizophrenia scales
      were most likely to be found among the profile leads, followed by the Depression,
      and to a lesser extent, the Hypochondriasis scales. According to the Friedman
      method, 30.9% of the records could be classified as 'spike', 'two-point code' or
      'three-point code'. The most striking finding of the study is that 40% of the
      profiles had four or more clinical scale elevations. Furthermore, 91% of those
      profiles with multiple elevations had elevations on both the neurotic and
      psychotic scales. This suggests that a substantial proportion of MMPI profiles in
      this sample are complex, and the clinical picture which they reflect requires a
      broader scope of psychological analysis beyond that of a single psychological
      mechanism.

PMID- 9530937
TI  - Non-epileptic attack disorder: a psychological perspective.
AB  - Due to the serious medical consequences in failing to recognize non-epileptic
      attack disorder (NEAD), and the frequency with which neurologists come into
      contact with such patients, clearly NEAD constitutes a major concern for
      clinicians in the field of epilepsy. This article presents the psychological
      characteristics of 185 patients with NEAD. Psychological factors that were
      identified as being important in the understanding of the development and
      maintenance of NEAD included: anxiety or stress; physical abuse; significant
      bereavement; family dysfunctioning; relationship problems; depression; sexual
      abuse. An absence of relevant psychological factors was found in only 5% of
      patients. From patients' descriptions of their attacks, it appears that many
      symptoms are related to anxiety. Our findings are largely supported by previous
      studies and their relevance to effective management and treatment of NEAD
      patients is discussed.

PMID- 9530938
TI  - Are what people know about their epilepsy and what they want from an epilepsy
      service related?
AB  - This study set out to investigate the level of knowledge about epilepsy in
      general and in relation to the patients' own condition, in patients attending a
      tertiary referral epilepsy outpatient clinic. It also sought to investigate
      patient satisfaction with the service and whether knowledge acquired about
      epilepsy related to that satisfaction. Seventy out of 94 patients responded to
      the Epilepsy Knowledge Profile Questionnaires (general and personal knowledge of
      epilepsy) and a questionnaire assessing service satisfaction. Patients were found
      to know more about epilepsy in general than about their own condition. In
      particular some patients were unable to give accurate indications of their drug
      regimes. Over 91% were satisfied with the serviced they received but this bore no
      relation to information they had acquired or wanted about epilepsy.
      Multidisciplinary services were requested by a sizeable percentage of patients
      but especially access to a specialist nurse in epilepsy. The study highlights the
      need for clinicians to check patients' knowledge about their condition and for
      further work to clarify the source of patients' satisfaction with service
      delivery.

PMID- 9530939
TI  - Neuropsychological test performance in frontal-lobe epilepsy: the influence of
      aetiology, seizure type, seizure frequency and duration of disorder.
AB  - Although frontal-lobe epilepsy accounts for a sizeable proportion of all partial
      epilepsies the neuropsychological characteristics have proved difficult to
      document. A possible explanation for this may lie in the impact of seizure
      related variables. However, these have rarely been addressed in a frontal-lobe
      epilepsy sample. In this report the neuropsychological sequelae of the aetiology
      of epilepsy, seizure spread, seizure frequency and duration of disorder were
      examined in a sample of 74 subjects with frontal-lobe epilepsy (42 with left, 32
      with right). Only a few significant results were revealed and in these cases the
      possibility of greater cortical dysfunction rather than specific frontal
      impairment would offer a viable solution. Further studies are needed in order
      that firmer conclusions concerning the impact of the variables investigated on
      neuropsychological performance in a sample of subjects with frontal-lobe epilepsy
      can be drawn.

PMID- 9530940
TI  - Auditory brainstem response, middle-latency response, and slow cortical potential
      in patients with partial epilepsy.
AB  - Auditory brainstem responses (ABRs), middle-latency responses (MLRs), and slow
      cortical potentials (SCPs) have been recorded in patients with partial epilepsy
      previously untreated by anticonvulsants. Peak latencies, interpeak intervals, and
      amplitudes were estimated and the mean group values were compared with the
      respective data in age- and gender-matched healthy individuals. Neither ABRs nor
      MLRs in the patients differed significantly from those in the control group.
      Conversely, the SCP characteristics demonstrated regular differences: the P2 peak
      latency in the patients was prolonged and both the P1N1 and N1P2 amplitudes were
      increased. Considering the mechanisms of the ABR and MLR, it has been suggested
      that the specific structures of central auditory pathway up to the primary cortex
      do not play any essential role in the pathogenesis of partial epilepsy.
      Furthermore, it is speculated that the SCP-generating cortical areas, being
      primarily of non-specific qualities, are intimately involved in the mechanisms of
      epilepsy.

PMID- 9530941
TI  - A survey of epilepsy-patient perceptions of video-game material/electronic
      screens and other factors as seizure precipitants.
AB  - The risk of seizures while playing video games in photosensitive (PS) individuals
      with epilepsy is well established. However, media reporting, game packaging and
      anecdotal advice of medical practitioners may have implicated a broader
      proportion of the epilepsy population, i.e. not just those with PS, to be at
      risk. By using a hospital outpatient survey this paper investigates the perceived
      risk of using video games and electronic screens among those individuals with
      epilepsy. More than a quarter of those surveyed indicated that they thought that
      a substantially greater proportion of people with epilepsy were at risk from this
      stimulus than the estimated real risk suggests. One in 13 perceived that every
      individual with epilepsy is at risk of a seizure as a result of playing video
      games. Our results also indicate that the proportion of individuals with epilepsy
      surveyed who saw themselves to be at risk from video games, is two to three times
      the estimated real risk. For many individuals seizures during video-game play
      will represent a chance occurrence without a causal link. It is essential that
      accurate information is passed on to every individual with epilepsy regarding
      their personal susceptibility to photic-induced seizures so that those who are
      not at increased risk may participate in relevant activities without undue
      concern.

PMID- 9530942
TI  - Seizure recurrence after a first generalized tonic-clonic seizure, in children,
      adolescents and young adults.
AB  - A sample of 78 patients (32 females and 46 males) who had a first unprovoked
      generalized tonic-clonic seizure between the age of 3 and 21 years was studied
      prospectively. Duration of follow-up was 2-10 years (mean 5.2 years). A second
      seizure occurred in 69.2% (54 of 78), most commonly (38 of 54, 70.37%) in the
      first three months after the first seizure. There were no significant differences
      in the total number of relapses among various aetiological groups. For idiopathic
      aetiology, seizure recurrence was significantly more common if the first seizure
      occurred during sleep (24 of 29, 82.75%) than in the waking state (5 of 13,
      17.25%). The second seizure occurred in the same state, i.e. night sleep or awake
      in 72.2% (39 of 54) of patients. The presence of epileptiform patterns in the
      first two EEGs in the waking state or in sleep was significantly associated with
      a highly increased risk of seizure recurrence.

PMID- 9530943
TI  - Piracetam prevents pentylenetetrazol kindling-induced neuronal loss and learning
      deficits.
AB  - The effect of the nootropic drug piracetam (100 mg/kg) on kindled seizures,
      kindling-induced learning deficits, and histological alterations due to changes
      in central excitability was investigated in Wistar rats. The animals were kindled
      by repeated i.p. injections of an initially subconvulsive dose of
      pentylenetetrazol (PTZ). As a control, piracetam or physiological saline was
      given 60 minutes before PTZ. Twenty-four hours after completion of kindling the
      rats were tested in a shuttle-box paradigm. Seven days after the final kindling
      injection, the animals received a challenge dose of PTZ. Finally, the brains of
      the rats were processed for histological investigation. Pentylenetetrazol-kindled
      animals showed increasing seizure scores, and a learning deficit in the shuttle
      box. Piracetam had no effect either on kindling development or on the reaction to
      a challenge dose of PTZ, but it protected the animals against the kindling
      induced reduction of learning performance. The substance had no effect on
      learning performance in control animals. In distinct hippocampal structures, a
      neuronal cell loss was found in kindled rats. Interestingly, piracetam
      counteracted this damage efficaciously. The effects of piracetam are discussed in
      terms of its cytoprotective action. It is suggested that a coadministration of
      piracetam with clinically used antiepileptic drugs might be useful in
      antiepileptic therapy.

PMID- 9530944
TI  - Time distribution of epileptic seizures during video-EEG monitoring. Implications
      for health insurance systems in developing countries.
AB  - An attempt was made to identify guidelines to help establish epilepsy monitoring
      units in developing countries. We assessed the time distribution of seizures
      during video-EEG monitoring and we also estimated the minimum time required for
      such a procedure and the impact of these variables upon the health insurance
      system. Mean time for recording five stereotyped clinical events was 72 hours,
      with a significant number of events recorded between midnight and 0600 hours (P <
      0.05). This pilot study may help to establish local policies that will warrant an
      adequate work-up for our patients.

PMID- 9530945
TI  - A survey of lamotrigine and vigabatrin treatment in children with severe
      epilepsy.
AB  - A retrospective survey was carried out of add-on treatment with lamotrigine (LTG)
      and vigabatrin (GVG) in 109 children with severe epilepsy, treated between 1987
      and 1994, identified from a total population of 300 patients seen annually, in a
      tertiary referral outpatient clinic in Cardiff, Wales. Of 79 patient treatments
      with LTG and 86 with GVG, 42 patients were treated with add-on LTG, 52 with add
      on GVG and 20 with both drugs simultaneously. A Kaplan-Meier curve, applied to
      each of the two index drugs, indicated that 71 and 62% of patients would be
      expected to continue taking LTG or GVG, respectively after 40 months. Improved
      seizure control (> or = 50%) at the time of audit was seen in 65% of LTG and 58%
      of GVG patient treatments for all epilepsy syndromes, but there was a higher
      proportion of patients with generalized epilepsy improved by LTG (28/41, 68%)
      than that improved by GVG (8/20, 40%), and only those with generalized epilepsy
      treated with LTG became seizure free (8/38, 21%). Similar proportions of patients
      discontinued LTG (16%) and GVG (15%) due to an adverse experience, but a higher
      proportion discontinued GVG (18%) compared with LTG (6%) because of lack of
      efficacy. This study supports the relative clinical effectiveness of LTG and GVG
      in the real world, where children with severe epilepsy are treated in clinical
      practice and serves to generate hypotheses to enable design of prospectively
      controlled trials, which should enable more rational use of these two drugs in
      the paediatric population with epilepsy.

PMID- 9530946
TI  - Benign familial neonatal convulsions: abnormal intrauterine movements,
      provocation by feeding and ICTAL EEG.
AB  - An infant with benign familial neonatal convulsions had abnormal movements during
      the last 2 months of pregnancy suggestive of intrauterine seizures. His postnatal
      seizures, one of which was captured by electroencephalography, had both partial
      and generalized features. Most seizures appeared to be provoked by feeding.

PMID- 9530947
TI  - A clinically recognizable neuronal migration disorder: congenital bilateral
      perisylvian syndrome. Case report with long-term clinical and EEG follow-up.
AB  - Congenital bilateral perisylvian syndrome (CBPS) is a recently described,
      neuronal migration disorder, characterized by pseudobulbar palsy, epilepsy and
      mental retardation and bilateral perisylvian dysplasia. A 15-year-old boy was
      diagnosed with CBPS according to the typical clinical, and magnetic resonance
      imaging (MRI) features. The patient was suffering from atypical absence seizures,
      repeating daily in spite of antiepileptic drug therapy, since age 7 years. He had
      also experienced rare generalized tonic-clonic seizures and complex partial
      seizures. Neurological examination showed severe restriction of tongue movements,
      severe dysarthria, dysphagia, facial diplegia, mild pyramidal signs and moderate
      mental retardation. A computed tomographic (CT) scan demonstrated bilateral
      perisylvian enlargement. The diagnosis was corrected with MRI after six years.
      Frequent irregular generalized spike and wave abnormalities and focal sharp and
      slow waves over the posterior regions of both hemispheres were shown by
      electroencephalograms (EEG). The patient was treated with Na-Valproate,
      carbamazepine and lamotrigine but did now show any significant change in seizure
      frequency in the eight-year follow-up period. Intractable seizures, mental
      retardation and particularly congenital pseudobulbar palsy suggest this
      congenital entity. Those patients who exhibit these typically clinical features,
      must have MRI.

PMID- 9530948
TI  - Lamotrigine after corpus callosotomy.

PMID- 9530949
TI  - An aggressive seizure and behavioural disorder following trivial head injury.
AB  - We report on a normal 6-year-old boy in whom a trivial head injury triggered a
      severe seizure, behavioural and cognitive disorder. Complete recovery occurred
      within 6 months. An aetiology such as trivial head injury is significant for
      prognosis as the outcome is invariably excellent.

PMID- 9530950
TI  - Isolated ataxia as an idiosyncratic side-effect under gabapentin.
AB  - Gabapentin has been accepted worldwide as a novel antiepileptic drug with a
      favourable tolerability profile. However, movement disorders have been reported
      previously as rare side-effects in individual patients. We report on two patients
      who developed isolated severe ataxia under low-dose gabapentin which resolved
      abruptly after discontinuation of the drug. This side-effect probably resembled a
      rare idiosyncratic adverse reaction. We propose the gabapentin-specific neuronal
      binding site which has a high density in the cerebellum as a possible mechanism
      of action and suggest that the initiation of gabapentin requires caution if pre
      existing cerebellar function impairment is evident.

PMID- 9530951
TI  - Structural study of N-linked sugar chains of sheep erythrocyte membrane
      glycoproteins.
AB  - Our previous study showed that non-reducing terminal galactose residues of N
      linked sugar chains present in sheep erythrocyte membrane glycoproteins are
      important for rosette formation with T lymphoblastic cells [Ogasawara et al.
      (1995) Immunol Lett 48: 35-38]. As a first step to elucidate the significant
      structures of sugar chains involved in rosette formation, we analysed N-linked
      sugar chains released from the membrane glycoproteins by hydrazinolysis. The
      oligosaccharides were labeled with NaB3H4 and fractionated using columns of
      Aleuria aurantia lectin-Sepharose, MonoQ and Bio-Gel P-4. Structural analyses of
      oligosaccharides by sequential exoglycosidase digestion in combination with
      methylation analysis revealed that the membrane glycoproteins contain bi- (19%),
      tri- (33%), and tetraantennary (44%) complex-type oligosaccharides and that the
      oligosaccharides having exposed galactose residues amount to 40% of the total.

PMID- 9530952
TI  - Kinetics of formation of GlcNAc-GlcNAc-P-P-dolichol by microsomes from the retina
      of the embryonic chick.
AB  - Little quantitative information is available concerning individual reactions of
      the dolichol pathway. We have investigated the kinetics of the GlcNAc-transferase
      that catalyzes the biosynthesis of GlcNAc-GlcNAc-P-P-dolichol using chemically
      synthesized GlcNAc-P-P-dolichol as the substrate. Using microsomal preparations
      from the retina of the embryonic chick as enzyme source, optimal incubation
      conditions of pH, metal ion and detergent concentrations were established, after
      which apparent kinetic constants (Km and Vmax) were determined under initial rate
      conditions for GlcNAc-P-P-dolichol and UDP-GlcNAc. These studies provide the
      first quantitative description of the kinetics of this reaction.

PMID- 9530953
TI  - Multiplex RT-PCR method for the analysis of the expression of human
      sialyltransferases: application to breast cancer cells.
AB  - In many cases of human cancer, the appearance of hypersialylated glycan
      structures is related to a precise stage of the disease; this may depend on
      altered regulation of one or more sialyltransferases genes. Since several
      distinct sialyltransferase enzymes arising from different unique genes transfer
      sialic acid residues in the same linkage onto the same acceptor, it is impossible
      to precisely determine which enzyme is involved in the observed phenotype based
      on enzymatic assays. We have developed a very sensitive and highly reproducible
      multiplex reverse transcriptase-polymerase chain reaction technique in order to
      monitor the expression of four human sialyltransferases genes ST6Gal I, ST3Gal I,
      ST3Gal III and ST3Gal IV in small cell samples. Multiplex PCR amplification using
      specific primers for each sialyltransferase and detection of amplification
      products by polyacrylamide gel electrophoresis is a method that is fast and easy
      to handle and has proven to be useful for establishing sialyltransferase patterns
      of expression in breast immortalized cell line HBL100 as well as in breast cancer
      cell lines MCF-7/6, MCF-7/AZ and MDA.

PMID- 9530954
TI  - Different modes of sialyl-Tn expression during malignant transformation of human
      colonic mucosa.
AB  - Monoclonal antibodies TKH2 and B72.3, which react with the mucin-associated
      sialyl-Tn(STn) antigen, preferentially bind to cancerous but not normal colonic
      tissues. If O-acetyl groups are removed by saponification of tissues, MAb TKH2
      will react with normal colonocytes, whereas MAb B72.3 remains non-reactive. To
      explain this difference in binding specificity, we tested both MAbs against
      synthetic constructs of single (monomeric) or clustered (trimeric) STn epitopes
      by enzyme immunoassay. Both MAb TKH2 and MAb B72.3 reacted with trimeric STn, but
      MAb TKH2 demonstrated greater binding than MAb B72.3 to monomeric STn. This
      suggests that normal colonic mucosa expresses monomeric STn epitopes, but that
      with transformation to malignancy, clustered STn epitopes appear. The appearance
      of clustered STn epitopes during colonic carcinogenesis represents a novel
      pattern of carbohydrate antigen expression and implicates alterations at the
      level of apomucins and/or glycosyltransferases responsible for cluster epitope
      formation.

PMID- 9530956
TI  - Development and characterization of an antibody directed to an alpha-N-acetyl-D
      galactosamine glycosylated MUC2 peptide.
AB  - In an attempt to raise anti-Tn antibodies, an alpha-N-acetyl-D-galactosamine
      glycosylated peptide based on the tandem repeat of the intestinal mucin MUC2 was
      used as an immunogen. The MUC2 peptide (PTTTPISTTTMVTPTPTPTC) was glycosylated in
      vitro using concentrated alpha-N-acetylgalactosaminyltransferases activity from
      porcine submaxillary glands which resulted in the incorporation of 8-9 mol of
      Ga/NAc. Rabbits and mice developed specific anti-MUC2-GalNAc glycopeptide
      antibodies and no detectable anti-Tn antibodies. Anti-glycopeptide antibodies did
      not show reactivity with the unglycosylated MUC2 peptide or with other GalNAc
      glycosylated peptides. A mouse monoclonal antibody (PMH1) representative of the
      observed immune response was generated and its immunohistological reactivity
      analysed in normal tissues. PMH1 reacted similarly to other anti-MUC2 peptide
      antibodies. However, in some cells the staining was not restricted to the
      supranuclear area but extended to the entire cytoplasm. In addition, PMH1 reacted
      with purified colonic mucin by Western blot analysis suggesting that PMH1 reacted
      with some glycoforms of MUC2. The present work presents a useful approach for
      development of anti-mucin antibodies directed to different glycoforms of
      individual mucins.

PMID- 9530957
TI  - Development of glycosylated human interleukin-1alpha, neoglyco IL-1alpha, by
      coupling with D-galactose monosaccharide: synthesis and purification.
AB  - In order to develop glycosylated cytokine, recombinant human IL-1alpha was
      chemically modified with galactose monosaccharide. Galactose with C9 spacer, 8
      (hydrazinocarbonyl)octyl beta-D-galactopyranoside (3), was synthesized by
      glycosylation of C9 spacer, methyl 9-hydroxynonanoate, with acetobromogalactose,
      followed by deacetylation and hydrazidation. Total yield of 3 was 43.6% in three
      steps. Compound 3 was coupled to IL-1alpha by the acyl azide method. The
      glycosylated IL-1 was purified by anion-exchange chromatography, and galactose
      coupled to IL-1 was confirmed by R. communis lectin blotting. Based on the
      molecular weight, the average number of carbohydrate molecules introduced per
      molecule of IL-1alpha was estimated to be 9.1.

PMID- 9530955
TI  - Purification and characterization of the MUC1 mucin-type glycoprotein, epitectin,
      from human urine: structures of the major oligosaccharide alditols.
AB  - The MUC1 glycoprotein, epitectin, a component of the human bladder epithelium,
      was purified from human urine. Sedimentation equilibrium analysis and gel
      filtration using polysaccharide or protein standards revealed a polydisperse
      preparation with molecular weights ranging from about 0.9 to 1.3 x 10(6). This
      suggests that in the native state epitectin exists as aggregates of three or four
      monomer units of 350-400 kDa. Epitectin was found to have significant affinity to
      hexyl-, octyl- or phenyl agarose indicating that hydrophobic interactions and
      possibly carbohydrate-carbohydrate interactions may be responsible for the self
      association. Chemical and enzymic deglycosylation of [125I]-labeled urine
      epitectin and metabolically labeled H.Ep.2 epitectin resulted in extremely
      polydisperse products. The buoyant densities of epitectin purified from urine and
      H.Ep.2 cells were found to be 1.39-1.40 g ml(-1), suggesting that the total
      carbohydrate content of these preparations is not significantly different. The O
      linked saccharides of epitectin were fractionated by HPLC and analyzed by
      permethylation and FAB-MS. The neutral saccharides from both sources contain
      three common structures, namely Gal1 --> 3GalNAc, GlcNAc1 --> 6 (Gal1 --> 3)
      GalNAc and Gal1 --> 4GlcNAc --> 6 (Gal1 --> 3)GalNAc. The sialic acid of urine
      epitectin consisted entirely of N-acetylneuraminic acid. The two sources of
      epitectin, in vitro labeled on sialic acid, were found to have the same sialyl
      oligosaccharides but in different proportions. Metabolic labeling and N-glycanase
      susceptibility experiments firmly established the presence of N-linked
      saccharides in epitectin as minor components. The remarkable similarities in the
      total carbohydrate content, the carbohydrate composition and structures of
      saccharides between epitectin from urine, a non-malignant source, and H.Ep.2
      cells is surprising in view of the prevailing view that MUC1 glycoproteins of
      cancer cells are underglycosylated compared to those produced by non-malignant
      cells.

PMID- 9530959
TI  - Polymer-supported tin carbohydrate chemistry.
AB  - It was anticipated that stannylation of carbohydrates could be achieved using tin
      on a polymer-support. Such immobilization simplifies the purification of the
      carbohydrate because the toxic tin reagent can be removed by filtration. In this
      case an alkene linker (3-buten-1-ol) was added to chloromethylated 2% cross
      linked polystyrene by etherification. Photochemical hydrostannylation with
      dibutyltinchlorohydride gave a polymer bound trialkyl tin chloride. The Sn-Cl
      could be hydrolysed with NaOH to yield a resin with terminal Sn-O bonds. Highly
      regioselective acylation of methyl alpha-D-mannopyranoside (alphaMeMan) to its 3
      O-benzoyl derivative was achieved. Traces of the mono 6-O-benzoate and the 3,6-di
      O-benzoate were also obtained. Methyl alpha-D-glucopyranoside was also
      selectively acylated to its 2-O-benzoate but this reaction gave a more complex
      mixture. The isolated yields (10-30% based on sugar) were disappointingly low.
      The yields were improved to about 60% with 5% cross-linked resin.

PMID- 9530958
TI  - Development of glycosylated human interleukin-1alpha, neoglyco IL-1alpha, by
      coupling with D-galactose monosaccharide: biological activities in vitro.
AB  - In the previous study, galactose with C9 spacer was chemically coupled to human
      recombinant (rh) IL-1alpha in order to study the effect of glycosylation on its
      activities, and to develop IL-1 with less deleterious effects. In this study we
      examined a variety of IL-1 activities in vitro, including proliferative effect on
      T cells, antiproliferative effect on myeloid leukemic cells and melanoma cells,
      stimulatory effects on IL-6 synthesis by melanoma cells and PGE2 synthesis by
      fibroblast cells Galactose-introduced IL-1alpha (Gal-IL-1alpha) exhibited reduced
      activities from 10 to 10000 times compared with unmodified IL-1alpha in all the
      activities performed in vitro. The competitive binding of 125I-IL-1alpha to mouse
      T cells and pre-B cells with unlabeled IL-1alpha s suggests a decrease in binding
      affinities of Gal-IL-1alpha to both type I and type II IL-1 receptors. Therefore,
      reduced activities of Gal-IL-1alpha are due, at least partially, to the decrease
      in their receptor binding affinities.

PMID- 9530960
TI  - Structures of the N-linked carbohydrate of ascorbic acid oxidase from zucchini.
AB  - The N-glycan moiety of ascorbic acid oxidase from zucchini (Cucurbita pepo) has
      been described to be a core-pentasaccharide with a xylose [D'Andrea et al. (1988)
      Glycoconjugate J 5:151-7]. Ascorbic acid oxidase is sometimes used to
      characterize antibodies directed against carbohydrate determinants on plant
      glycoproteins. To prevent misinterpretations of immunological data, the structure
      of the N-glycan of ascorbic acid oxidase has been reinvestigated. The
      oligosaccharides were released by almond N-glycosidase and analysed as their
      pyridylamino derivatives by 2D-HPLC and exoglycosidase digestions. The main
      structure resembled the typical complex plant N-glycan consisting of a core
      pentasaccharide decorated with xylose and 3-linked fucose. The other abundant
      species lacked the fucose residue. Small amounts of these glycans carried a
      GlcNAc residue on the 6-arm. Therefore, ascorbic acid oxidase will not only react
      with antibodies directed against the xylosylated region but also with those
      binding to N-glycans with 3-linked fucose.

PMID- 9530961
TI  - Structural characterization of the N-linked oligosaccharides derived from
      HIVgp120 expressed in lepidopteran cells.
AB  - The oligosaccharides of recombinant HIV gp120 expressed in lepidopteran Sf9 cells
      were analysed after hydrazine release by gel permeation and high pH anion
      exchange chromatography. N-Linked glycans were exclusively of the oligomannose
      series and no evidence for charged complex or hybrid type glycans was found.
      However a glycosylation reaction similar to those found in vertebrates was
      evident. The major glycoform of gp120, that comprised 30% of all the species
      analysed, was structurally identified by exoglycosidase digestion and found to be
      a core fucosylated structure, Manalpha1,6(Manalpha1,3)Manbeta1,4GlcNAc(Fucalpha1+
      ++,6)GlcNAc. Further confirmation of the ability of lepidopteran cells to
      fucosylate N-linked glycans was provided by an in vitro analysis of this reaction
      using authentic oligosaccharide substrates.

PMID- 9530962
TI  - HPLC method for the determination of Fuc to Asn-linked GlcNAc
      fucosyltransferases.
AB  - Mammalian cells often contain an enzyme which transfers fucose onto the reducing
      terminal GlcNAc (GlcNAc-1) of N-glycans with an alpha1,6-linkage. In plants, on
      the other hand, the fucose is transferred to GlcNAc-1 with an alpha1,3-inkage.
      Insect cells can exhibit both enzymatic activities. Hitherto, the activity of
      these fucosyltransferases has been determined by the incorporation of
      radioactively labelled fucose into an acceptor glycopeptide. This assay, however,
      cannot discriminate these two activities. Here we report on the use of dansylated
      glycoasparagine for the specific determination of 1,3- and 1,6
      fucosyltransferases. The two possible products and the substrate are separated on
      a reversed phase column and detected by fluorescence.

PMID- 9530964
TI  - Olfactory bulb output cell temporal response patterns to increasing odor
      concentrations in freely breathing rats.
AB  - This study compares the single-unit responses of 74 mitral/tufted cells recorded
      in freely breathing rats to step increases of the intensity of five odorants from
      2 x 10(-4) to 10(-1) of saturated vapor pressure. It reveals a stability of the
      responses of these olfactory bulb output cells. Olfactory stimulation has
      frequently been shown to produce a strong patterning of mitral/tufted cell
      discharges highly correlated with respiration. In this study, cells were
      generally found to show the same response type to two consecutive concentrations,
      and only a few cells switched their response from excitation to suppression or
      vice versa. Their firing peak and/or trough occupied the same position in a high
      proportion of respiratory cycles recorded during a stimulation, and they remained
      significantly time-locked to the same respiratory epoch for the next higher
      concentration. Increasing odor concentration did not cause the mean firing
      frequency of individual cells during a peak to change appreciably between
      successive or extreme concentrations. By contrast, it tended to shift their
      maximum frequency during this peak towards an earlier respiratory cycle after
      stimulation onset. These results are compared with data reported in other
      electrophysiological studies and with results given by olfactory bulb models
      before being discussed for their implications in odor coding.

PMID- 9530963
TI  - Characterization of a polyclonal anti-Galalpha1-3Gal antibody from chicken.
AB  - A polyclonal antibody was raised against the Galalpha1-3Gal carbohydrate epitope,
      which is expressed by all mammals (except man and the closest primate species) by
      immunizing hens with rabbit erythrocyte membranes. IgY was isolated from egg
      yolks, and affinity-purified on a Galalpha1-3Gal-Synsorb column. Two percent of
      the initial IgY fraction was recovered. The specificity of the affinity-purified
      antibody was characterized by: absorption with human, rabbit and pig
      erythrocytes; by using Synsorb columns; by inhibition with different saccharides;
      and by immunostaining of glycolipids separated on thin layer chromatograms. A
      weak reactivity was found toward blood group B or blood group Pk determinant,
      depending on the assay system used. Such reactivities were abolished after
      absorption by the appropriate sorbents, yielding a polyclonal anti-Galalpha1-3Gal
      antibody with narrow specificity.

PMID- 9530965
TI  - Infants' exploration of scented toys: effects of prior experiences.
AB  - To evaluate breastfed infants' responses to scented objects, we videotaped the
      facial and bodily reactions of sixty-three infants as they explored, in
      succession, three toys that were identical in appearance but different in their
      characteristic odor. Two of the toys were scented with odorants previously shown
      to be transmitted to human milk, one with ethanol and the other with vanilla,
      whereas the third toy was unscented. Each videotape was subjected to frame-by
      frame analysis to measure a variety of behaviors that are considered either to be
      exploratory in nature in that they lead to perceptual information about the
      object or to reflect the infants' hedonic reaction. Analyses of these behaviors
      revealed that the infants looked more and vocalized less in the presence of the
      vanilla-scented toy and spent less time manipulating the ethanol-scented toy when
      compared with the unscented toy. Moreover, differential exposure to the odors of
      ethanol and vanilla, as indicated by differential consumption of alcohol by a
      parent or use of vanilla-scented product by the mother, was related to
      differential responses to these odors. These findings suggest that human infants
      are able to detect and retain information about the chemical features of their
      environment.

PMID- 9530966
TI  - Attention and the detectability of weak taste stimuli.
AB  - Subjects detected weak solutions of sucrose or citric acid under conditions in
      which attention was directed toward one of the tastants or the other. Detection
      thresholds were measured using an adaptive, forced-choice procedure, with a three
      down one-up rule, which computer simulations suggest should be more reliable than
      the popular two-down one-up rule. The thresholds were modestly but systematically
      lower for attended tastants than for unattended ones. Similar results have been
      reported in other sense modalities, including vision (greater sensitivity to
      stimuli presented to attended versus unattended spatial locations) and hearing
      (greater sensitivity to stimuli presented at attended versus unattended sound
      frequencies). Taken together, the findings are consistent with a general
      hypothesis regarding attention in sensory systems: gains or losses in
      detectability occur when a central attentional mechanism (or, conceivably, a
      preattentive mechanism) selectively and preferentially monitors signals arising
      from particular subsets of peripheral neural inputs.

PMID- 9530967
TI  - Differences in perception of everyday odors: a Japanese-German cross-cultural
      study.
AB  - There is a growing appreciation that experience with odors may strongly influence
      their perception. To further investigate this, the responses of 40 Japanese and
      44 age-matched German women to everyday odorants were compared. Subjects were
      presented with 18 stimuli in squeeze bottles and asked to rate them according to
      intensity, familiarity, pleasantness and edibility, to describe associations
      elicited by them and, if possible, to name them. One-third of the odorants were
      presumed to be familiar to the Japanese only, one-third to the Germans and one
      third to both populations. Significant differences were found between the two
      populations on all measures. Better performance by the Japanese in providing
      appropriate descriptors for 'Japanese' odorants and by the Germans for 'European'
      odorants supported the pre-selection of stimuli as culture-typical. Particularly
      clear differences between the two populations were found in pleasantness ratings.
      In general, a positive relationship was found between pleasantness and judgement
      of stimuli as edible, suggesting that culture-specific experiences-particularly
      of foods-may significantly influence odor perception. Somewhat unexpectedly,
      significant differences were also found between the two populations in intensity
      ratings for some odorants. These differences did not seem simply to be artefacts
      of the test situation and raise the possibility that experience may even
      influence such basic aspects of odor perception as stimulus intensity.

PMID- 9530968
TI  - The peripheral olfactory organ of the zebrafish, Danio rerio: an ultrastructural
      study.
AB  - The peripheral olfactory organ of the adult zebrafish, Danio rerio, was
      investigated by light as well as scanning and transmission electron microscopy.
      The olfactory organ consists of several lamellae that insert into a midline
      raphe, thus forming an oval-shaped rosette. Sensory and nonsensory regions are
      located separately on each lamella. The olfactory epithelium contains three types
      of receptor cells: two as described classically for other fishes, bearing either
      cilia or microvilli, the third being a new sensory cell type--the crypt cell. The
      crypt cell has no olfactory knob but bears microvilli as well as submerged cilia.
      Its axon travels together with the axons of the other receptor cells towards the
      basal lamina. Whereas the classical receptor cells are separated by supporting
      cells with small protrusions on their apical surfaces, the crypt cell is always
      surrounded by one or two specialized electron-lucent supporting cells which also
      bear microvillous-like apices. The nonsensory areas contain the goblet cells,
      ciliated nonsensory cells and epidermal cells with microridges.

PMID- 9530969
TI  - Scanning electron microscopy and gramicidin patch clamp recordings of
      microvillous receptor neurons dissociated from the rat vomeronasal organ.
AB  - Vomeronasal organs from female rats were dissociated and isolated microvillous
      receptor neurons were studied. The isolated receptor neurons kept the typical
      bipolar shape which they have in situ as observed by scanning electron
      microscopy. We applied the perforated patch-clamp technique using the cation
      selective ionophore gramicidin on freshly isolated and well differentiated
      receptor neurons. The mean resting potential was -58+/-14 mV (n=39). The
      contribution of the sodium pump current to the resting potential was demonstrated
      by lowering the K+ concentration in the bath or by application of 100 microM
      dihydro-ouabain. The input resistance was in the range of 1-6 GOmega and
      depolarizing current pulses of a few pA were sufficient to trigger overshooting
      action potentials. In voltage clamp conditions a fast transient sodium inward
      current and a sustained outward potassium current were activated by membrane
      depolarization. These observations indicate that freshly isolated vomeronasal
      receptor neurons of rats can be recorded, using gramicidin, with little
      modification of the intracellular content. Their electrophysiological properties
      are very similar to those observed in situ. Four out of eight female vomeronasal
      receptor cells were depolarized by diluted rat male urine.

PMID- 9530970
TI  - Sensory evaluation of mixtures of maltitol or aspartame, sucrose and an orange
      aroma.
AB  - The suitability of Beidler's mixture equation for mixtures of sucrose and
      maltitol as well as for mixtures of sucrose and aspartame was examined in the
      presence of an orange aroma. The mean scores for the attribute sweet remained
      constant for each combination of sucrose and maltitol and for each combination of
      sucrose and aspartame. Therefore, Beidler's mixture equation can be used to
      choose combinations of sucrose and maltitol and of sucrose and aspartame giving
      the same sweetness. Quantitative descriptive analysis of different solutions
      indicated that the flavour profiles of sucrose and maltitol did not differ
      significantly at a constant concentration of orange aroma. However, flavour
      profiles of solutions with increasing aspartame concentrations (but constant
      aroma levels) showed significantly higher scores for the attributes sour,
      chemical and aftertaste. Addition of orange aroma provided the different
      solutions with a more distinct flavour. The mean scores for the attributes
      orange, sour, fruity and aftertaste increased significantly for most of the
      sucrose-maltitol mixtures. This effect of orange aroma was even more pronounced
      in solutions containing combinations of sucrose and aspartame. Further comments
      on the attribute aftertaste showed similar terms for the different solutions, the
      most often mentioned being orange, sour, fruity and chemical for solutions
      containing the orange aroma. The aftertaste of solutions containing relatively
      more aspartame was mainly described as sweet and chemical.

PMID- 9530971
TI  - Protein-bound male urinary pheromones: differential responses according to age
      and gender.
AB  - The attractive properties of male urinary pheromones were tested on adult or
      prepubertal male and female mice. An androgen-dependent protein is present in
      adult male urine (major urinary protein, MUP) which has been suggested to be a
      pheromone-binding protein. We tested the pheromonal properties of the protein
      bound volatiles in a test of attractiveness. These molecules, that co-purify with
      MUP, attract females and repel adult males. In prepubertal animals, females are
      repelled and males are attracted by the same stimuli. These results are similar
      to those obtained by others with adult male whole urine. Therefore MUP binds
      molecules with a pheromonal activity, and these molecules are sufficient to act
      as male signals.

PMID- 9530972
TI  - Human responses to propionic acid. I. Quantification of within- and between
      participant variation in perception by normosmics and anosmics.
AB  - The objective of this study was to fully characterize normosmic perception of
      stimuli expected to cause widely varying degrees of olfactory and nasal
      trigeminal stimulation and to directly evaluate the possible role of olfactory
      nerve stimulation in nasal irritation sensitivity. During each of four identical
      test sessions, four anosmic and 31 normosmic participants were presented with a
      range of concentrations extending from peri-threshold for normosmics to supra
      threshold for anosmics. For each session, odor (O) and nasal irritation (NI)
      sensitivities were summarized in terms of the concentrations required to produce
      four sensation levels ('iso-response' concentrations). Within-participant
      variation in these iso-response concentrations was < 10-fold for 95% of
      normosmics, for both O and NI. For O but not NI, these apparent fluctuations in
      sensitivity were largely accounted for by the uncertainty surrounding the iso
      response concentrations calculated for each session. Anosmics exhibited minimal
      within- and between-participant variation in NI and required, for all but the
      highest perceptual level, a higher concentration than almost all normosmics.
      Between-participant variation, expressed in terms of 90% confidence interval
      widths, was approximately 0.5 log units for both O and NI for the highest
      perceptual level, but increased to approximately 0.8 and 1.8 log units,
      respectively, for the lowest (peri-threshold) level. Our findings suggest that:
      (i) most apparent variation over time in O sensitivity is actually a reflection
      of the uncertainty surrounding estimates of sensitivity obtained for each
      session; (ii) within- and between-participant variation in O sensitivity is far
      less than is commonly reported; and (iii) low to moderate levels of NI in
      normosmics are the result of relatively weak trigeminal stimulation combined with
      much greater olfactory activation.

PMID- 9530973
TI  - Separation, characterization and sexual heterogeneity of multiple putative
      odorant-binding proteins in the honeybee Apis mellifera L. (Hymenoptera: Apidea).
AB  - According to precise molar mass determined by mass spectrometry and N-terminal
      sequence, some 25 odorant-binding-like proteins were characterized from the
      antennae and legs of worker and drone honeybees. Antennal specific proteins,
      composed of six different molecules, were classified into three subclasses
      according to N-terminal sequence homology. The major sexual difference was shown
      to lie in the relative abundance of these antennal specific proteins and in the
      occurrence of a drone-specific isoform. At least 19 other related proteins were
      found to occur in antennae and legs, forming another class showing homology with
      insect OBP. Genotype comparison of two honeybee races revealed a variability
      limited to this second class. Provided that these odorant-binding-like proteins
      are indeed able to bind odorants or pheromones, the question of whether their
      peculiar multiplicity contributes to the remarkable capacity of the honeybee to
      discriminate among a wide range of odor molecules is raised.

PMID- 9530974
TI  - Sweet and sweetness-inducing activities of new triterpene glycosides, strogins.
AB  - In a previous study we isolated homologues of new oleanane-type triterpene
      glycosides from leaves of Staurogyne merguensis Kuntze and named them strogins.
      Strogins themselves have a sweet taste (sweet activity), which diminishes in a
      few minutes. Subsequent application of cold water to the mouth then elicits a
      sweet taste (sweetness-inducing activity). In the present study we systematically
      examined the properties of the sweet and sweetness-inducing activities of
      strogins. Strogins 1, 2 and 4 had both the sweet and sweetness-inducing
      activities, while strogins 3 and 5 had no activities. The sweetness-inducing
      activity in response to cold water lasted for 1 h for strogin 2 and 2 h for
      strogins 1 and 4. The sweetness-inducing activity was immediately diminished by
      application of gamma-cyclodextrin to the mouth after strogins were held in the
      mouth. It seems that the strogins were adsorbed on the gustatory receptor
      membranes and eliminated by inclusion activity of gamma-cyclodextrin. The
      structure of strogin resembles that of gymnemic acid, which has antisweet
      activity. There was competition between strogin 1 and gymnemic acid; treatment of
      the tongue with strogin 1 before application of Gymnema extract to the mouth
      reduced the antisweet activity. While the sweetness-inducing activity of curculin
      in response to water was suppressed by the presence of divalent cations such as
      Ca2+ or Mg2+, that of strogin was not suppressed by the divalent cations. The
      changes in the inactive complex between strogin and the sweet receptor site in
      the adaptation state into the active complex induced by cold stimulation were
      discussed.

PMID- 9530975
TI  - Flux detectors versus concentration detectors: two types of chemoreceptors.
AB  - Dose-response curves relating the external stimulus concentration to receptor
      occupancy differ in two types of chemoreceptor organs. In 'concentration
      detectors' the receptor molecules at the receptor cell membrane are directly
      exposed to the external stimulus concentration; these organs exhibit the well
      known hyperbolic dose-response relationship reflecting the association
      dissociation of stimulus and receptor molecules. In contrast, 'flux detectors'
      accumulate the stimulus molecules in a perireceptor compartment. In flux
      detectors, deactivation of stimulus molecules may be in balance with arrival, as
      a prerequisite for producing a constant effective stimulus concentration at
      constant adsorptive flux of stimulus molecules. In a simple model of a flux
      detector in which receptor molecules themselves catalyze the deactivation, the
      dose-response relationship is linear. It reflects the rate of stimulus
      deactivation. If the deactivation is catalyzed by a separate enzyme, the dose
      response relationship can be close to hyperbolic, or linear. In all cases, the
      receptor molecules are maximally occupied if the adsorptive flux equals or
      exceeds the maximum rate of stimulus deactivation. The time course of the
      receptor potential recorded from moths' pheromone receptors depends on the odor
      compound, which suggests that a peripheral process, possibly the stimulus
      deactivation, is the slowest, rate-limiting process of the transduction cascade.
      Further evidence comes from experiments with stimuli oversaturating the mechanism
      responsible for the decline of the receptor potential.

PMID- 9530976
TI  - Assessment of odor annoyance and its relationship to stimulus concentration and
      odor intensity.

PMID- 9530977
TI  - Social isolation induces preference for odours of oestrous females in sexually
      naive male staggerer mutant mice.
AB  - The staggerer murine mutation induces olfactory deficits. Mutant males do not
      prefer oestrous odours to anoestrous ones. A period of social isolation after
      weaning induces such a preference in mutants.

PMID- 9530978
TI  - Aqueous stability of SB 210661: kinetics and primary degradation mechanisms of an
      N-hydroxyurea-containing 5-lipoxygenase inhibitor.
AB  - SB 210661, (S)-N-hydroxy-N-[2,3-dihydro-6-(2,6-difluorophenylmethoxy)-3-benzo
      furanyl]urea, is a potent and selective inhibitor of 5-lipoxygenase. Its aqueous
      stability was primarily evaluated to support development of analytical methods
      and formulations. The results also add to the growing database on the stability
      of N-hydroxyurea compounds. Comparison of the stability of SB 210661 with that of
      two other N-hydroxyurea-containing compounds, zileuton and Abbott-79175,
      supported a common primary degradative pathway at pH > 5 and different
      degradative pathways at pH < 5. The pathway at pH > 5 is consistent with the
      hydrolysis of the N-hydroxyurea group, whereas for SB 210661, the pathway at pH <
      5 is consistent with specific acid-catalysed nucleophilic displacement of the N
      hydroxyurea group by water.

PMID- 9530979
TI  - Spectrophotometric and spectrofluorimetric determination of fluorouracil in the
      presence of its degradation products.
AB  - Three reliable spectrophotometric and spectrofluorimetric procedures are
      described for the determination of fluorouracil in bulk powder and ampoules in
      the presence of its degradation products. One spectrophotometric procedure, based
      on measurement at 555 nm of the violet-coloured complex formed by fluorouracil
      with cobalt(II), has a detection limit of 0.03 mg mL(-1). Two sensitive
      spectrofluorimetric procedures are also proposed. One is based on measurement of
      the intrinsic fluorescence of the liberated fluorouracil at 375 nm, after
      precipitation as its cobalt(II) complex, decomposition of the precipitate with
      sulphuric acid and excitation at 295 nm. The second depends on excitation of the
      fluorouracil-cobalt(II) complex at 395 nm and measuring its fluorescence at 483
      nm. The limits of detection of the two spectrofluorimetric procedures are 0.5 and
      2 microg mL(-1), respectively. The three procedures have been used successfully
      for the determination of fluorouracil ampoules. The validity of the methods has
      been assessed by applying the standard addition technique.

PMID- 9530980
TI  - Effect of particle size and coating level on the diffuse reflectance of wax
      matrices.
AB  - The aim of this study was to examine the influence of particle size and extent of
      coating on the diffuse-reflectance spectra of wax matrices containing embedded
      potassium chloride. Near-infrared spectroscopy was used to analyse the diffuse
      reflectance characteristics of the prepared multi-particulate matrices without
      destructive sample preparation. A 2-factor, 3-level face-centred central
      composite design was selected to construct a second-order polynomial model which
      described the effect of particle size and amount of coating on the intensity of
      the diffusely reflected light. A non-linear model was used to demonstrate the
      effect of the selected parameters on the intensity of the reflected light; good
      correlation was obtained between experimental and predicted results. The results
      indicated that the extent of coating and the particle size of the examined
      systems in the selected particle size-range modified the intensity of the
      reflected light. It can be concluded that near-infrared spectroscopy is a
      sensitive means of measuring not only the particle size of powders (substrates
      and their mixtures), but also that of coated multi-particulate systems.

PMID- 9530981
TI  - An investigation of the mechanism of flux across polydimethylsiloxane membranes
      by use of quantitative structure-permeability relationships.
AB  - Quantitative structure-permeability relationships (QSPRs) based on readily
      calculated parameters have been developed to study penetration across a
      polydimethylsiloxane membrane. Maximum steady-state flux values for 256 compounds
      through a polydimethylsiloxane membrane were taken from previous studies. Forty
      three physicochemical parameters were calculated for each compound and their
      significance to flux determined. Removal of fourteen outliers enabled derivation
      of a significant three-parameter QSPR based on the number of hydrogen-bond
      acceptor and donor groups and sixth-order path molecular connectivity. Models
      based on parameters important for penetration across human skin (log P and
      molecular weight) were comparatively poor. This model suggests that the mechanism
      of flux across a polydimethylsiloxane membrane is based mainly on hydrogen
      bonding effects; as such it occurs via a mechanism of action different from that
      of penetration of the skin in man.

PMID- 9530982
TI  - Transdermal delivery and accumulation of indomethacin in subcutaneous tissues in
      rats.
AB  - Oral non-steroidal anti-inflammatory drugs (NSAIDs) are effective pharmacotherapy
      for a wide variety of painful, inflammatory disorders. Development of an
      efficient means of topical administration of NSAIDs could increase local soft
      tissue and joint concentrations while reducing systemic distribution of the drug,
      thereby reducing side-effects. With this in mind we studied the effects of a
      novel topical penetration enhancer for lipophilic compounds, a trans-phase
      delivery system (TPDS), a solution of benzyl alcohol, isopropanol and acetone, on
      the distribution of indomethacin in various tissues locally and remote from the
      site of application. We compared the TPDS with a 50:50 (v/v) mixture of propylene
      glycol and ethanol, a commonly used penetration enhancer, and with oral
      administration. We found that the TPDS was significantly superior to the other
      approaches at achieving high local-tissue concentrations in the vicinity of the
      site of application. In addition, comparison of these two carrier systems seems
      to clarify the different aqueous and hydrophobic pathways of drug penetration
      which emerge from various experimental findings and theoretical considerations.
      Our results suggest that this non-aqueous solvent system, and benzyl alcohol in
      particular, because of its unique physicochemical and solvating characteristics,
      might be able to deliver therapeutic levels of indomethacin to tissues close to
      the site of application in a safer and more effective manner than presently
      accepted forms of delivery.

PMID- 9530983
TI  - Evaluation of oral mucoadhesive microspheres in man on the basis of the
      pharmacokinetics of furosemide and riboflavin, compounds with limited
      gastrointestinal absorption sites.
AB  - When sustained-release adhesive and non-adhesive microspheres which release the
      same drugs at similar rates are administered orally, drug absorption after
      administration of adhesive microspheres should, if the gastrointestinal residence
      of adhesive microspheres is prolonged as a result of mucoadhesion, be higher than
      that after administration of non-adhesive microspheres. The gastrointestinal
      transit of oral adhesive microspheres in man has been evaluated
      pharmacokinetically using furosemide and riboflavin, compounds with limited
      absorption sites in the upper small intestine. In a preliminary experiment with
      fasted rats it was confirmed that a higher percentage of the drug remained in the
      stomach and that plasma drug levels were higher when furosemide was administered
      in the form of adhesive rather than non-adhesive microspheres. Two kinds of
      sustained-release microsphere, adhesive and non-adhesive, containing furosemide
      and riboflavin in hard gelatin capsules were prepared and orally administered to
      10 healthy fasted volunteers in a cross-over design. Areas under the plasma
      concentration-time curves (AUC) were 1.8 times larger for furosemide and urinary
      recovery was 2.4 times higher for riboflavin when adhesive microspheres rather
      than when non-adhesive microspheres were used. When adhesive microspheres
      containing riboflavin were administered to fed volunteers, urinary recovery was
      2.1 times higher and mean residence time (MRT) was more prolonged than when the
      microspheres were administered to fasted volunteers. Adhesive microspheres were
      found to adhere to the gastric or intestinal mucosa with high affinity in man and
      rats, resulting in prolonged gastrointestinal residence.

PMID- 9530984
TI  - Intestinal absorption of stable cyclic dipeptides by the oligopeptide transporter
      in rat.
AB  - Intestinal absorption of four cyclic dipeptides was studied in the everted small
      intestine of the rat. Cyclic seryltyrosine (cyclo(Ser-Tyr)) was stable enough to
      be transported whereas linear seryltyrosine was not. The absorption clearance of
      cyclo(Ser-Tyr) was concentration-dependent, and for cyclo(Ser-Tyr) at 125 microM
      decreased in the presence of glycylsarcosine (10 mM) or cephalexin (10 mM), which
      were reported to be absorbed by oligopeptide transporter. The absorption
      clearance was also reduced at 4 degrees C and in the presence of 1 mM
      dinitrophenol. Kinetic analysis of cyclo(Ser-Tyr) absorption showed that Km and
      Vmax were 19.8 microM and 0.295 nmol min(-1) cm(-1), respectively. It was also
      suggested that cyclic aspartylphenylalanine and cyclic histidylphenylalanine were
      absorbed by oligopeptide transporters, but cyclic histidylproline was not. The
      absorption clearance of cyclo(Ser-Tyr) in the control was much higher than the
      value of the correlation line representing a plot of passive transport (which was
      obtained from the absorption clearance of cyclic peptides in the presence of
      glycylsarcosine (10 mM)) against hydrophobicity (oil-water partition
      coefficient). These results indicate that cyclo(Ser-Tyr) is absorbed by the
      oligopeptide transporter.

PMID- 9530985
TI  - The pharmacokinetics and bioavailability of dihydroartemisinin, arteether,
      artemether, artesunic acid and artelinic acid in rats.
AB  - The pharmacokinetics and bioavailability of dihydroartemisinin (DQHS), artemether
      (AM), arteether (AE), artesunic acid (AS) and artelinic acid (AL) have been
      investigated in rats after single intravenous, intramuscular and intragastric
      doses of 10 mg kg(-1). Plasma was separated from blood samples collected at
      different times after dosing and analysed for parent drug. Plasma samples from
      rats dosed with AM, AE, AS and AL were also analysed for DQHS which is known to
      be an active metabolite of these compounds. Plasma levels of all parent compounds
      decreased biexponentially and were a reasonable fit to a two-compartment open
      model. The resulting pharmacokinetic parameter estimates were substantially
      different not only between drugs but also between routes of administration for
      the same drug. After intravenous injection the highest plasma level was obtained
      with AL, followed by DQHS, AM, AE and AS. This resulted in the lowest steady
      state volume of distribution (0.39 L) for AL, increasing thereafter for DQHS
      (0.50 L), AM (0.67 L), AE (0.72 L) and AS (0.87 L). Clearance of AL (21-41 mL
      min(-1) kg(-1)) was slower than that of the other drugs for all three routes of
      administration (DQHS, 55-64 mL min(-1) kg(-1); AM, 91-92 mL min(-1) kg(-1); AS,
      191-240 mL min(-1) kg(-1); AE, 200-323 mL min(-1) kg(-1)). In addition the
      terminal half-life after intravenous dosing was longest for AL (1.35 h), followed
      by DQHS (0.95 h), AM (0.53 h), AE (0.45 h) and AS (0.35 h). Bioavailability after
      intramuscular injection was highest for AS (105%), followed by AL (95%) and DQHS
      (85%). The low bioavailability of AM (54%) and AE (34%) is probably the result of
      slow, prolonged absorption of the sesame-oil formulation from the injection site.
      After oral administration, low bioavailability (19-35%) was observed for all five
      drugs. In-vivo AM, AE, AS and AL were converted to DQHS to different extents; the
      ranking order of percentage of total dose converted to DQHS was AS (25.3-72.7),
      then AE (3.4-15.9), AM (3.7-12.4) and AL (1.0-4.3). The same ranking order was
      obtained for all formulations and routes of administration. The drug with the
      highest percentage conversion to DQHS was artesunic acid. Because DQHS has
      significant antimalarial activity, relatively low DQHS production could still
      contribute significantly to the antimalarial efficacy of these drugs. This is the
      first time the pharmacokinetics, bioavailability and conversion to DQHS of these
      drugs have been directly compared after different routes of administration. The
      results show that of all the artemisinin drugs studied the plasma level was
      highest for artelinic acid; this reflects its lowest extent of conversion to DQHS
      and its slowest rate of elimination.

PMID- 9530986
TI  - Pharmacokinetics and haemodynamic effect of diltiazem in rats: effect of route of
      administration.
AB  - Diltiazem is a calcium antagonist widely used for the treatment of angina and
      hypertension. Previous studies in patients have shown that the haemodynamic
      effects of diltiazem are greater after parenteral rather than oral
      administration. The rat has been used as an animal model to determine the effect
      of the route of administration on the pharmacokinetic and haemodynamic effects of
      diltiazem. The results showed that plasma concentrations of diltiazem were more
      than 10 times higher after the intra-arterial dose. The plasma concentrations of
      the major metabolites were also higher after intra-arterial administration,
      although only for deacetyl diltiazem (M1) did the difference reach statistical
      significance (P < 0.05). The haemodynamic effects (on blood pressure and heart
      rate) of diltiazem were considerably greater after intra-arterial administration;
      this was attributed mainly to the much higher plasma concentrations of diltiazem.
      The hypotensive and chronotropic effects of diltiazem were similar; Emax and EC50
      for diastolic blood pressure were 72+/-19% and 4.4+/-5.9 microg mL(-1); for heart
      rate they were 77+/-32% and 10.0+/-11.7 microg mL(-1), respectively. The
      haemodynamic effects of diltiazem are much greater after intra-arterial
      administration, mainly because of the much higher plasma concentrations of the
      drug. The contribution by the metabolites would be minimal after this route of
      administration.

PMID- 9530987
TI  - Effect of sequence of administration on the pharmacokinetic interaction between
      the anticholinergic drug biperiden and [3H]quinuclidinyl benzylate or [3H]N
      methylscopolamine in rats.
AB  - In rats the pharmacokinetic interactions between the anticholinergic drug
      biperiden and [3H]quinuclidinyl benzylate ([3H]QNB) or [3H]N-methylscopolamine
      ([3H]NMS) is affected by the sequence in which the drugs are administered. Drug
      concentrations in various tissues were determined after intravenous
      administration of [3H]QNB or [3H]NMS (325 ng kg(-1)). Biperiden (6.4 mg kg(-1))
      was administered either 5 min before, concomitantly with or 20 min after
      injection of [3H]QNB or [3H]NMS. When biperiden was administered concomitantly
      with or before [3H]QNB, distribution of [3H]QNB among the regions of the brain
      and other tissues was reduced; at 4 h the ratio of the distribution of [3H]QNB
      for experimental animals to that for control animals ranged from 0.15 to 0.9.
      When biperiden was administered after [3H]QNB, the distribution of [3H]QNB in the
      brain and other tissues was significantly higher than for the other two
      treatments (P < 0.01). However, for [3H]NMS the sequence of administration had no
      effect on the distribution of the drug in the brain and other tissues except for
      the kidney. In-vitro, in crude synaptosomal membranes, the amount of [3H]QNB at 2
      h relative to the control concentration at equilibrium was 87% when biperiden was
      added before [3H]QNB and 56% when biperiden was added after [3H]QNB. In both
      instances the concentration of [3H]NMS reached equilibrium within 30 min. These
      findings suggest that the difference between the rate constant of association and
      dissociation at the possible site of action gives rise to the effect of the
      sequence of administration on the pharmacokinetic interaction.

PMID- 9530988
TI  - Analgesic and thermic effects, and cerebrospinal fluid and plasma
      pharmacokinetics, of intracerebroventricularly administered morphine in normal
      and sensitized rats.
AB  - The relationship between asthma and opioids has barely been investigated. This
      study examines whether active sensitization of rats changes the analgesic and
      thermic effects of intracerebroventricular morphine or the pharmacokinetics of
      the drug. Morphine (5, 10 and 20 microg) was given intracerebroventricularly to
      sensitized (active immunization to ovalbumin and Al(OH)3 then airway challenge
      with ovalbumin after 12 days) and normal (i.e. non-sensitized) male Sprague
      Dawley rats. The tail-flick latencies and changes in colon temperature were
      determined before morphine injection and at 30 min intervals for a period of 300
      min afterwards. Results were expressed as the area under the time-response curve.
      The analgesic and hyperthermic response to morphine for sensitized rats was less
      than that obtained for normal rats. Cerebrospinal fluid and blood samples were
      collected periodically for a period of 240 min and morphine levels were
      determined by a highly sensitive radioimmunoassay. The pharmacokinetic parameters
      half-life, terminal elimination rate constant and the mean residence time were
      determined in both cerebrospinal fluid and plasma by non-compartmental analysis.
      The area under the cerebrospinal fluid concentration-time curve from time zero to
      infinity was higher for sensitized rats than for normal rats for all three doses
      of morphine but these differences did not correspond with similar changes in
      pharmacological responses. In conclusion, the attenuated analgesic and thermic
      responses to intracerebroventricular morphine in the sensitized rats might be a
      result of pharmacodynamic alterations rather than to pharmacokinetic changes.

PMID- 9530989
TI  - Sodium nitroprusside enhances contractions of the guinea-pig isolated vas
      deferens.
AB  - The effects of sodium nitroprusside on the electrical and mechanical properties
      of the smooth muscle of the guinea-pig vas deferens, and its responses to
      transmitter substances, have been investigated by use of the sucrose-gap
      technique. Isolated longitudinal segments of guinea-pig vas deferens contracted
      in response to electrical field stimulation (100 V, 0.04-0.1 ms, 1-5 Hz, 10 s
      train every 60 s) and application of ATP (1 mM) or noradrenaline (10 microM).
      Sodium nitroprusside (0.1 mM) did not affect resting tension but did enhance
      contractions evoked by electric-field stimulation but not by ATP or
      noradrenaline. The sodium nitroprusside-induced enhancement was unaffected by the
      nitric oxide synthase inhibitor, Nomega-nitro-L-arginine methyl ester (L-NAME)
      (0.1 mM). Conversely, electrically evoked contractions were unaffected by the
      nitric oxide precursor L-arginine (1 mM) or the nitric oxide donor S-nitroso-N
      acetyl-DL-penicillamine (SNAP) (0.1 mM). The amplitudes of electrically evoked
      excitatory junction potentials (EJPs) were not affected by application of sodium
      nitroprusside, although it caused a small depolarization of 0.7+/-0.3 mV.
      Similarly, the depolarization caused by exogenous application of ATP or
      noradrenaline was unaffected by the presence of sodium nitroprusside. L-NAME, L
      arginine and SNAP did not affect EJP amplitude or baseline membrane potential. It
      is concluded that sodium nitroprusside enhances electrically evoked contractions
      of the guinea-pig vas deferens by reducing the threshold voltage for action
      potential firing in smooth-muscle cells.

PMID- 9530990
TI  - Differential effects of nicorandil on the vasodepressor responses to vasoactive
      polypeptides administered intravenously to rats.
AB  - The effects of nicorandil on vasodepressor responses to vasoactive intestinal
      polypeptide (VIP), calcitonin gene-related peptide (CGRP) and substance P have
      been examined in anaesthetized rats. Intravenous bolus injections of VIP (0.3
      microg kg(-1)), CGRP (0.1 microg kg(-1)) and substance P (0.1 microg kg(-1))
      induced reductions of blood pressure accompanied by slight increases (less than
      5%) in heart rate. Nicorandil infused intravenously at 10 or 30 microg kg(-1)
      min(-1) significantly augmented the vasodepressor responses to VIP and CGRP but
      did not modify the responses to substance P and acetylcholine (0.1 microg kg(
      1)). Intravenous treatment with glibenclamide (20 mg kg(-1)) [corrected]
      significantly attenuated not only the vasodepression caused by VIP and CGRP, but
      also the enhancement of the effects of the agents by nicorandil. These results
      indicate that nicorandil can enhance the action of VIP and CGRP, in rats, at
      least partly through ATP-sensitive K+-channel activation.

PMID- 9530991
TI  - Affinity constants and beta-adrenoceptor reserves for isoprenaline on cardiac
      tissue from normotensive and hypertensive rats.
AB  - To determine whether there are differences in cardiac beta-adrenoceptor
      responsiveness, isoprenaline affinity constants and fractional beta-adrenoceptor
      occupancy-response relationships for isoprenaline in the early stages of
      established hypertension, we studied the effects of bromoacetylalprenololmenthane
      (BAAM) and ([3,5-diamino-6-chloro-N-(1[N-beta-(2-hydroxyl-3-alpha-naphthoxypropy
      lamino)ethylcarbamoyl]-1-methylethyl)-pyrazine-2-carboxamide (ICI 147 798),
      slowly reversible beta-adrenoceptor antagonists, on the isoprenaline responses of
      the left ventricular papillary muscle and the left and right atria of 6-month-old
      Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). The papillary
      muscles, but not the right and left atria, of the SHR were less responsive to
      isoprenaline than those of the WKY. The isoprenaline pD2 values (the negative
      logarithms of the molar concentrations of agonist producing 50% of the maximum
      response) were 7.72 and 8.00 on the SHR and WKY papillary muscles, respectively.
      On the WKY papillary muscle the isoprenaline KA values were 2-3 x 10(-6) M, which
      is as expected for isoprenaline at beta1 or beta2-adrenoceptors. Isoprenaline had
      100-fold greater affinity on the WKY and SHR left atria than on the papillary
      muscles; the isoprenaline KA values were 2-4 x 10(-8) M. On the WKY papillary
      muscle and left atrium, isoprenaline had to occupy 3-4% of the beta-adrenoceptors
      to produce a 50% maximum response; on the WKY papillary muscle and left atrium
      isoprenaline had to occupy 25-35% and 55%, respectively, of the beta
      adrenoceptors to produce a 90% maximum response. The SHR papillary muscles and
      left atrium had smaller beta-adrenoceptor reserves for isoprenaline than did the
      WKY tissues. We were unable to obtain isoprenaline KA values on the WKY right
      atrium. The isoprenaline KA value on the SHR right atrium was 1-4 x 10(-8) M.
      Because the isoprenaline KA values for the left and right atria are markedly
      different from those previously reported for isoprenaline at beta1 or beta2
      adrenoceptors, we suggest that atypical beta-adrenoceptors might be present on
      the atria of WKY and SHR. We have also demonstrated a lower beta-adrenoceptor
      reserve on SHR papillary muscle and atria in the early stages of established
      hypertension.

PMID- 9530992
TI  - A study of the anti-pyretic effect of quinine, an alkaloid effective against
      cerebral malaria, on fever induced by bacterial endotoxin and yeast in rats.
AB  - The effect of quinine on fever induced by lipopolysaccharide and brewer's yeast
      has been investigated in rats. Oral administration of 50 or 100 mg kg(-1)
      quinine, doses which had no effect on normothermic rats, significantly reduced
      lipopolysaccharide- (50 microg kg(-1), i.m.) and yeast- (2 g kg(-1)) induced
      fever in rats. Pentoxifylline (100 mg kg(-1)), a tumour necrosis factor
      antagonist also attenuated the febrile response induced by lipopolysaccharide,
      but not that by yeast, in a manner similar to quinine. Piroxicam (5 mg kg(-1)), a
      cyclooxygenase inhibitor suppressed both types of fever with a longer duration of
      action. In addition to its anti-pyretic effect, quinine had a significant anti
      inflammatory effect in the carrageenan model of acute inflammation in the hind
      paw of rats. The results indicate the anti-inflammatory and anti-pyretic
      potential of quinine which might be important in addition to its anti-plasmodial
      action in the therapy of cerebral malaria.

PMID- 9530993
TI  - Effects of Sho-saiko-to on the pharmacokinetics and pharmacodynamics of
      tolbutamide in rats.
AB  - Although Sho-saiko-to (Xiao Chai Hu Tang), a major Chinese traditional medicine,
      is frequently prescribed with other synthetic or biotechnological drugs for the
      treatment of various chronic diseases, there is a dearth of information about
      interactions between sho-saiko-to and co-administered drugs. This paper reports
      the effects of Sho-saiko-to on the pharmacokinetics and glucose responses of a
      sulphonylurea hypoglycaemic agent, tolbutamide, after their oral administration
      in rats. After oral administration of tolbutamide (50 mg kg(-1)) with or without
      Sho-saiko-to extract powder (300 mg kg(-1)) to male Sprague-Dawley rats
      cannulated in the jugular vein, plasma tolbutamide and glucose levels were
      periodically measured. Co-administration of Sho-saiko-to tended to elevate the
      plasma tolbutamide concentration in the absorption phase. A two-compartment lag
      time model was found to describe the plasma tolbutamide concentration-time data.
      The maximum concentration of tolbutamide was significantly increased and time to
      reach the maximum concentration was reduced to about 70% by co-administration
      with Sho-saiko-to. There was no significant change in area under the curve or in
      the elimination half-life of tolbutamide. The extent of the lowering effect of
      tolbutamide on plasma glucose levels was increased up to 0.75 h and decreased
      after 5 h after co-administration of Sho-saiko-to. In conclusion, these studies
      suggest that sho-saiko-to slightly hastens the gastrointestinal absorption of
      tolbutamide. Furthermore, it is considered that elevation of the gastrointestinal
      absorption rate by Sho-saiko-to might potentiate the hypoglycaemic effect of this
      sulphonylurea in the early period after oral administration.

PMID- 9530994
TI  - Extensive binding of the bioflavonoid quercetin to human plasma proteins.
AB  - Although the bioflavonoids, a large group of polyphenolic natural products, exert
      chemopreventive effects in cardiovascular disease and cancer, there is little
      information about the disposition of these dietary components in man. The
      objective of this study was to investigate the plasma-protein binding of the most
      abundant bioflavonoid, quercetin, using 14C-labelled quercetin. An
      ultracentrifugation assay (170,000 g for 16 h at 20 degrees C) was shown to
      sediment plasma proteins. Binding of quercetin to normal plasma was extensive
      (99.1+/-0.5%, mean +/- s.d., n = 5). The unbound fraction varied as much as 6
      fold, 0.3-1.8%, between subjects. This high binding was independent of quercetin
      concentration over the range 1.5-15 microM (0.5-5 microg mL(-1)). Human serum
      albumin was the primary protein responsible for the binding of quercetin in
      plasma (99.4+/-0.1%). Binding by alpha1-acid glycoprotein (39.2+/-0.5%) and very
      low-density lipoproteins (<0.5% of total quercetin) did not make substantial
      contributions to overall plasma binding. The equilibrium association constant for
      the binding of quercetin to serum albumin was 267+/-33 x 10(3) M(-1) (n = 15).
      Thermodynamic data for the binding of quercetin to serum albumin indicated
      spontaneous, endothermic association. Displacement studies suggested that in man
      the 'IIA' subdomain binding site of human serum albumin was the primary binding
      site for quercetin. Association of quercetin with erythrocytes was significantly
      (P < 0.001) reduced by plasma protein binding. These data indicate poor cellular
      availability of quercetin because of its extensive binding to plasma proteins.

PMID- 9530995
TI  - Induction of axon-like and dendrite-like processes in neuroblastoma cells.
AB  - Neuroblastoma cells are widely utilized models for the study of the neuritic
      outgrowth phase of neuronal differentiation, but relatively few such studies have
      attempted to identify the nature of the process outgrowths. This identification
      will be necessary in developing strategies for utilizing these models to
      distinguish the underlying mechanisms involved in axonogenesis vs
      dendritogenesis. In an effort to identify procedures for inducing specific types
      of neurite outgrowth, and for distinguishing axon- from dendrite-like processes,
      we have subjected two neuroblastoma cell lines to a variety of stimuli previously
      shown to induce neurite outgrowth in these cells. These include neuraminidase,
      ionomycin, KCl+dibutyryl cAMP, cholera toxin B subunit, retinoic acid, dibutyryl
      cAMP (alone), GM1 ganglioside, and low serum. The first four of these (group 1)
      gave rise to neurites with axon-like characteristics, including immunostaining
      that was positive for phosphorylated high molecular weight neurofilament protein
      (NF-H) and synaptic vesicle protein-2 (SV2), but negative for microtubule
      associated protein-2 (MAP2). The next three treatments (group 2) resulted in
      dendrite-like processes, as evidenced in immunostaining that was positive for
      MAP2 and negative for NF-H and SV2. Neurites produced by low serum had mixed
      properties. These cytoskeletal differences were supported by immunoblot analysis
      with antisera to the above cytoskeletal proteins. Striking morphological
      differences were also noted, group 2-induced neurites being significantly shorter
      with more branch points than those generated by group 1 stimulants. Time of
      exposure to stimulatory agent was crucial in determining expression of the
      neuritic phenotype. Correlation with previous studies suggests that axon-like
      neurites result from stimulants which elevate intracellular Ca2+, a dependence
      not previously reported to our knowledge. Dendrite-like process outgrowth, on the
      other hand, does not appear to depend on altered intracellular Ca2+.

PMID- 9530996
TI  - Heterogeneous patterns of oligodendroglial differentiation in the forebrain of
      the opossum Didelphis marsupialis.
AB  - The differentiation of oligodendrocytes in the forebrain of the opossum
      (Didelphis marsupialis) has been studied by the immunohistochemical
      identification of 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) and by
      the autoradiographic detection of the uptake of 3H-thymidine. CNPase is expressed
      early in oligodendroglia somata and fibre sheaths (myelin) in the forebrain and
      its persistence in the cell bodies is regionally heterogeneous, being ephemeral
      in cells within the optic pathway, supraoptic decussation, and posterior
      commissure, of intermediate duration in the mamillo-thalamic fascicle, and stria
      medullaris, and long-lasting in other diencephalic and in telencephalic tracts.
      In the cerebral cortex, most CNPase+ cells have small somata and multiple
      processes (types I and II). CNPase-expressing oligodendrocytes are also
      regionally heterogeneous in terms of proliferative capability, which could not be
      detected in forebrain tracts or diencephalon, but has appeared in a small
      proportion of cells in the neocortical white matter and in the fimbria. Our
      findings provide additional evidence in favour of the heterogeneity of
      oligodendrocytes.

PMID- 9530997
TI  - Hyaluronectin is produced by oligodendrocytes and Schwann cells in vitro.
AB  - A hyaluronectin (HN)-like antigen was found in rat O-2A progenitors and
      oligodendrocytes, as well as in Schwann cells and in their culture medium. The HN
      like antigen secreted in culture supernatants had a higher molecular mass than HN
      extracted from rat brain at acidic pH. In vitro the secreted HN-like antigen was
      spontaneously and slowly degraded into species whose Mr was close to that of HN
      found in acidic brain extract. In brain or nerve neutral pH extracts, both HN
      like antigen and HN were present. The high Mr of the secreted antigen, the
      homology in amino acid sequences between HN and N-terminal domain of PG
      M/versican, in addition to a positive hybridization between Schwann cell RNAs and
      a probe obtained with primers derived from HN sequences also found in versican
      suggested that HN is closely related to the large proteoglycan PG-M/versican. The
      presence in Schwann cell extract of a HN mRNA whose Mr was compatible with the
      size expected for HN showed that HN may be directly secreted by cells and not
      only the consequence of a proteolytic cleavage. The similarity of HN with PG-M
      (V3) suggested that HN found in vivo could be the result of an alternative
      splicing of a single gene. We conclude that HN as other members of the PG
      M/versican family is a marker of oligodendrocytes and Schwann cells in culture.

PMID- 9530998
TI  - Differential distribution of a second type of tyrosine hydroxylase immunoreactive
      amacrine cell in the chick retina.
AB  - A second population of tyrosine hydroxylase-immunoreactive amacrine cells was
      demonstrated in embryonic and adult chicken retinas by immunohistochemistry
      techniques in whole flat-mount preparations. The populations were differentiated
      on a basis of different immunostaining intensities, levels of stratification in
      the inner plexiform layer, and topographical distributions. Cells of one type
      were similar to the previously described dopaminergic amacrine cells, denoted
      here as tyrosine hydroxylase type 1 cells. Immunoreactive neurons of the second
      type observed in the present work had relatively smaller somata size, and weaker
      immunostaining than type 1 cells, and were located preferentially in the ventral
      retina. These tyrosine hydroxylase type 2 cells could be visualized from
      embryonic day 14 to 21 days after hatching animals. The distribution of the
      second population was coincident with that of the targets of centrifugal fibres
      and with cells involved in long proprioretinal connections. We propose that the
      tyrosine hydroxylase type 2 amacrine cells found in the ventral retina could
      mediate an important pathway to the upper half of the visual field so as to aid
      in the detection of predators.

PMID- 9530999
TI  - Do aluminium and/or glutamate induce Alz-50 reactivity? A light microscopic
      immunohistochemical study.
AB  - Alzheimer's disease is thought to be characterized by conformational and
      phosphorylation changes in tau protein, leading to the formation of aggregations
      of paired helical filaments within neurons. Potential agents for inducing
      conformational changes in tau, namely aluminium and glutamate, were investigated
      in this study. Explant cultures of cortical neurons were established from
      embryonic day 17 rat fetuses. Cultures were exposed to aluminium, glutamate,
      aluminium/glutamate, aluminium/citric acid and citric acid (since aluminium is
      thought to enter cells via the transferrin receptor by complexing with citric
      acid) from 7-12 days in vitro. Control explants were exposed to basal medium
      only. On day 12, explants were paraffin-embedded. Four-six explants were serially
      sectioned per condition. For each explant, every 10th and adjacent 4 microm
      section were randomly selected and processed, with controls, for: (1) alcoholic
      morin histochemistry (to detect intracellular aluminium), (2) Perls' iron
      histochemistry (to control for the morin stain which also detects iron), (3)
      neurofilament immunohistochemistry (to estimate total neuronal number per
      explant) and (4) Alz-50 immunohistochemistry (to detect possible conformational
      changes in tau). The absolute number of stained/immunoreactive neurons was
      determined per explant. The percentage incidence was then determined per explant
      and averaged per condition. Explants in the aluminium conditions contained
      significant increases in the incidence of morin-positive aluminium containing
      neurons. There was also a significant increase in the incidence of Alz-50
      positive neurons for the aluminium compared with control explants. These results
      suggest: (1) aluminium enters neurons and (2) aluminium alone induces possible
      conformational changes in tau as detected by the Alz-50 antibody, while aluminium
      combined with glutamate, or glutamate alone, do not.

PMID- 9531000
TI  - Do aluminium and/or glutamate induce Alzheimer PHF-like formation? An electron
      microscopic study.
AB  - Paired helical filaments (PHFs) constitute the majority of filaments in
      neurofibrillary tangles (NFTs), an Alzheimer's disease (AD) characteristic. PHFs
      consists of two filaments helically twisted around one another in a regular
      pattern. The effects of possible PHF-inducing candidates, namely aluminium and
      glutamate, were observed at the ultrastructural level in this investigation. Rat
      cerebral explants were exposed to aluminium, citric acid and glutamate singly or
      combined from 7-12 days in vitro (DIV), while control explants remained in basal
      medium. On 12 DIV, explants were processed for EM. Three-four EM explants were
      serially sectioned per condition. Ten 60 nm sections from five systematically
      sampled areas per explant were collected. One section was randomly chosen per
      sampled area and all neurons within it observed at 81,200x to record the presence
      of accumulations of curved filaments (CFs), straight filaments (SFs) or PHFs.
      Using stereological methods, absolute numbers and the percentage incidence of CFs
      and SFs were calculated. A significant increase in the frequency of neurons
      containing CF aggregations in aluminium explants compared to glutamate explants
      was found. There were no significant differences between conditions for neurons
      containing SF accumulations. Possible PHFs were observed in one
      aluminium/glutamate-treated explant. These results suggest that aluminium alone
      can cause significant formation of accumulations of C- or S-shaped CFs, some of
      which are double-stranded and twisted around one another regularly. However,
      structures that were possibly PHF-like were only observed in one aluminium
      treated explant, thus making it premature to draw an association between
      aluminium and the induction of AD-like pathology.

PMID- 9531001
TI  - Cortisol and affective responses to exercise.
AB  - It has been reported that physically active individuals demonstrate attenuated
      cortisol responses to acute exercise compared to inactive individuals.
      Furthermore, a number of studies have demonstrated that increased cortisol levels
      are associated with negative affective states. Conversely, low cortisol levels
      have been demonstrated to be related to positive psychological constructs such as
      self-efficacy. However, the roles of activity history and adrenocortical activity
      in affective responses to acute exercise have not been examined. We therefore
      compared salivary cortisol, perceived exertion and affective responses to acute
      exercise in 13 male cross-country runners and 13 non-runners. The experimental
      trial consisted of a 30 min treadmill run at 60% VO2 max. Cortisol and affective
      responses were assessed before, during and after exercise; ratings of perceived
      exertion (RPEs) were recorded during exercise. Analyses of variance indicated no
      significant group differences in cortisol responses. However, there was a main
      effect for time (P< 0.05), with cortisol increasing from baseline to the 29th
      minute of exercise and then decreasing to 30 min post-exercise. Non-runners
      possessed greater perceptions of effort and negative affect during exercise
      compared to cross-country runners. Furthermore, the RPEs were positively related
      to post-exercise cortisol levels (P< 0.05), and affect and cortisol responses
      were inversely related 30 min post-exercise (P< 0.05). These results provide
      partial support for the hypothesis that cortisol levels are related to exercise
      induced affective states.

PMID- 9531002
TI  - Pathological versus physiological left ventricular hypertrophy: a review.
AB  - Left ventricular hypertrophy is recognized as an independent risk factor for
      cardiovascular morbid events. The primary mechanisms responsible for stimulating
      it are unknown. Epidemiological theories suggest that left ventricular
      hypertrophy is a continuous variable with no threshold, while morphological
      studies argue that it is the structure, or quality, and function of the
      myocardium (and therefore non-continuous), not the quantity of the myocardial
      mass, that poses the cardiovascular risk. Although left ventricular hypertrophy
      has been classically viewed as an adaptive response of the cardiovascular system
      to an imposed load, it has been demonstrated that haemodynamic overloading in
      selected hypertensive patients is not the sole determinant of left ventricular
      structure and function. Pathological and physiological states of left ventricular
      hypertrophy have been described primarily using criteria focusing on normal
      chamber performance and oxygen delivery as well as the reversibility of the
      hypertrophy once the overload is removed. Both states are also defined by the
      nature of the imposed load and the resulting myocardial adaptations. This review
      addresses the pathological and physiological states of left ventricular
      hypertrophy, the hypertrophy patterns, and the corresponding structural and
      functional characteristics, together with some of the biochemical factors thought
      to influence remodelling.

PMID- 9531003
TI  - Influence of fluid intake pattern on short-term recovery from prolonged,
      submaximal running and subsequent exercise capacity.
AB  - The aim of this study was to examine if the pattern of fluid intake with a
      carbohydrate-electrolyte solution during 4 h recovery from prolonged, submaximal
      running would influence the subsequent endurance capacity. Seven well-trained
      athletes aged 19.8 +/- 0.3 years (mean +/- s(mean)) took part in the study, which
      had university ethical committee approval. They ran at 70% VO2 max on a level
      treadmill for 90 min (T1), or until volitional fatigue, whichever came first, on
      two occasions, at least 7-10 days apart. Four hours later, the subjects ran at
      the same speed for as long as possible (T2), as a measure of their endurance
      capacity. During the 4 h rehydration recovery period, the runners were allowed to
      drink a carbohydrate-electrolyte solution (6.9% Lucozade-Sport; sodium, 24 mmol
      l(-1); potassium, 2.6 mmol l(-1); calcium, 1.2 mmol l(-1); osmolality, 300 mOsm
      kg(-1)) ad libitum on one occasion. On the other occasion, the volume of the same
      fluid was prescribed from calculations of the body mass loss during T1 (2.6% of
      pre-exercise body mass). All subjects completed the 90 min run during T1 on both
      trials. However, during T2, in the prescribed intake trial, the exercise time to
      exhaustion was 16% longer (P< 0.05) than during T2 in the ad libitum trial (69.9
      +/- 9.1 vs 60.2 +/- 10.2 min). Although there was no difference between
      conditions in the total volume ingested (1499 +/- 155 vs 1405 +/- 215 ml), the
      volume of carbohydrate-electrolyte solution ingested in the fourth hour of the
      rehydration recovery period was greater in the prescribed intake trial than in
      the ad libitum trial (258 +/- 52 vs 78 +/- 34 ml; P< 0.05). The amount of glucose
      ingested in this period during the prescribed intake trial was also greater than
      during the ad libitum trial (17.8 +/- 3.6 vs 5.4 +/- 2.4 g; P< 0.05). There was a
      higher blood lactate concentration at the start of T2 in the prescribed intake
      trial than in the ad libitum trial (1.12 +/- 0.20 vs 0.94 +/- 0.09 mmol l(-1); P<
      0.05), but there were no differences in blood glucose, plasma insulin, free fatty
      acid concentrations or urine volume between trials. The results of this study
      suggest that drinking a prescribed volume of a carbohydrate-electrolyte solution
      after prolonged exercise, calculated to replace the body fluid losses, restores
      endurance capacity to a greater extent than ad libitum rehydration during 4 h of
      recovery, even though the total volumes ingested were the same between trials.

PMID- 9531004
TI  - Perceived motivational climate and cognitive and affective correlates among
      Norwegian athletes.
AB  - Based on Ames' conception of situational goal structures, the present study
      investigated whether achievement-related cognitions and affect were related to
      specific motivational climates. The participants were 148 experienced students in
      team sport at a Norwegian university who responded to a questionnaire on their
      perceptions of the motivational climate in their sport, use of learning
      strategies, satisfaction, sources of satisfaction and perceived purposes of
      participating in sport. Canonical correlation analysis revealed that the
      perception of the motivational climate as either mastery- or performance
      involving was related to reporting of affect, achievement strategies and
      perceived purposes of sport in a conceptually consistent manner. Controlling for
      dispositional goals, regression analyses, in which the athletes' dispositional
      achievement goals were controlled, showed that perception of a performance
      oriented climate emerged as a negative and unique predictor of satisfaction or
      interest in addition to the variance accounted for by ego orientation. Athletes
      who perceived the motivational climate as mastery-oriented endorsed mastery as a
      source of satisfaction, and were less inclined to report avoiding practice. In
      addition, athletes who perceived the climate as mastery-oriented believed that
      sport may develop lifetime skills. In contrast, perceiving the climate as
      performance-oriented was positively related to status as a perceived purpose of
      team sport. Our findings suggest that, when athletes perceive the sport climate
      as task-involving, it facilitates the adoption of adaptive learning strategies,
      the use of controllable criteria to determine satisfaction, and enhances
      perception of sport as being important for developing lifetime skills.

PMID- 9531005
TI  - Hip and shoulder rotations during the golf swing of sub-10 handicap players.
AB  - The motion of the shoulders, arms and club during the golf swing has often been
      explained using the 'double pendulum' model. Despite subsequent explanations for
      the actions of the distal segments of the body, the coordination of more proximal
      segments during the swing is less well understood. To ascertain the pattern of
      centre of mass motion and hip and shoulder rotations that result in a high
      clubhead speed at impact, the swing used in driving from the tee of eight low
      handicap golfers was videotaped and analysed using three-dimensional techniques.
      The shoulders rotated in excess of 90 degrees during the backswing and, in 75% of
      the golfers, continued rotating away from the flag as the hips began turning back
      towards it. This sequential pattern of hip and shoulder rotation indicated that
      they conformed to the 'summation of speed' principle, which is hypothesized to
      result in a greater torque being applied to the club before impact. The speed of
      the drive was also benefited by the centre of mass shifting exclusively in the
      intended direction of ball flight during impact.

PMID- 9531006
TI  - Contribution of the lower extremity joints to mechanical energy in running
      vertical jumps and running long jumps.
AB  - The energy contribution of the lower extremity joints to vertical jumping and
      long jumping from a standing position has previously been investigated. However,
      the resultant joint moment contributions to vertical and long jumps performed
      with a running approach are unknown. Also, the contribution of the
      metatarsophalangeal joint to these activities has not been investigated. The
      objective of this study was to determine the mechanical energy contributions of
      the hip, knee, ankle and metatarsophalangeal joints to running long jumps and
      running vertical jumps. A sagittal plane analysis was performed on five male
      university basketball players while performing running vertical jumps and four
      male long jumpers while performing running long jumps. The resultant joint moment
      and power patterns at the ankle, knee and hip were similar to those reported in
      the literature for standing jumps. It appears that the movement pattern of the
      jumps is not influenced by an increase in horizontal velocity before take-off.
      The metatarsophalangeal joint was a large energy absorber and generated only a
      minimal amount of energy at take-off. The ankle joint was the largest energy
      generator and absorber for both jumps; however, it played a smaller relative role
      during long jumping as the energy contribution of the hip increased.

PMID- 9531007
TI  - The association between status and cohesion in sport teams.
AB  - The main objective of this study was to establish the relationship between
      perceptions of status attributes and cohesion and status ranking and cohesion. A
      secondary aim was to determine whether age (operationalized by scholastic levels)
      or culture serves as a moderator in the relationship between either status
      attributes or status ranking and cohesion. Another secondary aim was to determine
      if differences are present in the importance attached by athletes to status
      attributes. Canadian and Indian athletes were tested. Although perceptions of the
      importance of status attributes and cohesiveness were related, the effect size
      was small (Green, 1991); perceptions of status ranking and cohesiveness were not
      related. Neither scholastic level nor culture served as a moderator in the
      association between either status attributes or status rank and cohesion. The
      importance that athletes attach to status attributes is similar between
      scholastic levels and across cultures. The results are discussed in terms of the
      role of status in sport teams.

PMID- 9531008
TI  - Molecular aspects of poliovirus biology with a special focus on the interactions
      with nerve cells.
AB  - Poliovirus (PV), the pathogenic agent of paralytic poliomyelitis, is the
      prototype of the picornavirus family. Although paralytic poliomyelitis has been
      nearly totally eradicated in most industrialized countries, PV continues to be an
      important public health problem in many developing countries. Moreover, in
      industrialized countries, two current concerns are the occurrence, albeit at a
      very low frequency, of vaccine-associated paralytic poliomyelitis, due to the
      genetic instability of the attenuated oral PV strains in vaccines, and the
      emergence of a neuro-muscular pathology in many survivors of the acute disease,
      called the post-polio syndrome. PV has been targeted by the World Health
      Organization for world-wide eradication in the coming decade and continues to be
      the subject of intensive research. The advances made in the molecular biology of
      PV, taken together with the development of new animal and cell models, have
      permitted a new look at a key step in the pathogenesis of poliomyelitis, i.e. the
      interactions between PV and nerve cells. These aspects of PV biology are
      developed in this review according to three themes: (i) the PV host range; (ii)
      the molecular determinants of PV neurovirulence and attenuation; and (iii) the
      persistence of PV in nerve cells, which has proven to be an interesting new
      domain in the field of PV research.

PMID- 9531009
TI  - The comparative biology of latent herpes simplex virus type 1 and type 2
      infections: latency-associated transcript promoter activity and expression in
      vitro and in infected mice.
AB  - HSV-1 and HSV-2 express abundant latency-associated transcripts (LATs) without
      which these viruses reactivate in animals inefficiently. To further characterize
      the importance of LATs to the comparative biology of latent HSV-1 and -2
      infections, we assessed the relative activities of the viral LAT promoters in
      vitro using transient transfection assays, and the accumulation of LATs in vivo
      using a mouse ocular infection model. In vitro, the HSV-2 LAT promoter proved to
      be six to tenfold more potent than the HSV-1 promoter in driving reporter gene
      expression. In mice HSV-1 and -2 achieved comparable levels of virus replication
      in the eye, but HSV-2 grew to higher titers than HSV-1 in trigeminal ganglia and
      brain. Quantitative-competitive DNA and RNA (RT) PCR and in situ hybridization
      showed that ganglia latently infected with HSV-2 contained sixfold more copies of
      DNA (P=0.003), eightfold more LATS (P=0.01), and ninefold more LAT in situ
      positive neurons. However, the numbers of LATs per latent genome were equivalent
      for both viruses. Although the HSV-2 LAT promoter is more potent than the HSV-1
      promoter in transient expression assays, the accumulation of HSV-1 and 2 LATs in
      mouse trigeminal ganglia is comparable.

PMID- 9531010
TI  - Neuroinvasion by ovine lentivirus in infected sheep mediated by inflammatory
      cells associated with experimental allergic encephalomyelitis.
AB  - Maedi Visna Virus (MVV) is a prototypic lentivirus that causes infection only in
      cells of macrophage lineage, unlike the primate lentiviruses which infect both
      CD4+ T lymphocytes and macrophages. In primates, the earliest viral invasion is
      associated with the ability of the virus to infect and activate T cells which
      convey virus to the brain. Infected monocytes in blood rarely cause CNS infection
      in absence of activation of CD4+ T cells. In the face of lack of infection or
      activation of T cells by MVV in sheep, the question arises, how does MVV gain
      access to the brain to cause the classical lesions of visna? In previous studies
      on experimental induction of visna, sheep were inoculated with virus directly in
      the brain. In this study, we asked whether neuroinvasion by MVV would occur if
      sheep were inoculated with virus in a non-neural site. Nine sheep were inoculated
      intratracheally and all developed systemic infection when examined 3 weeks later.
      At this time, five were injected intramuscularly with brain white matter
      homogenized in Freund's complete adjuvant to induce EAE. None of the four animals
      inoculated with virus alone developed CNS infection despite typical lentiviral
      infection in lungs, lymphoid tissues and blood-borne mononuclear cells. In
      contrast, all five of the sheep injected with brain homogenate developed
      infection in the brain. Virus was produced by macrophages associated with the EAE
      lesions. This study illustrated that both activated T cells specific for antigen
      in the CNS and infected macrophages are essential for lentivirus
      neuropathogenesis.

PMID- 9531011
TI  - The human polyomavirus, JCV, does not share receptor specificity with SV40 on
      human glial cells.
AB  - The initial event in the life cycle of a virus is its interaction with specific
      receptors present on the surface of a cell. Understanding these interactions is
      important to our understanding of viral tropism and tissue specific pathology
      associated with viral disease. The human polyomavirus, JCV, is the etiological
      agent of the fatal central nervous system (CNS) demyelinating disease,
      progressive multifocal leukoencephalopathy (PML). PML is the direct result of JCV
      infection of oligodendrocytes, the myelin producing cell in the CNS. In vivo, JCV
      can be detected in oligodendrocytes, astrocytes, lymphoid tissue, and peripheral
      blood of PML patients. In vitro, JCV infects human glial cells, tonsilar stromal
      cells, and, to a limited extent, human B lymphocytes. The initial step in
      infection of cells by JCV is at the level of attachment and entry. A specific
      cell surface receptor for JCV on human glial cells has not been identified. To
      begin to understand the nature of JCV receptors on human glial cells, large
      quantities of a previously characterized hybrid JC virus (Mad-1/SVEdelta) were
      purified. A direct virus binding assay demonstrated that these highly purified
      and labeled JCV virions bound to a finite number of cellular receptors on human
      glial cells. A competitive virus binding assay demonstrated that an excess of
      unlabeled JCV competed with labeled JCV more efficiently than did an excess of
      purified SV40. Furthermore, anti-class I antibodies which inhibited infection of
      glial cells by SV40 had no significant effect on infection by JCV. These results
      imply that JCV does not share receptor specificity with the related polyomavirus,
      SV40.

PMID- 9531012
TI  - Progressive multifocal leukoencephalopathy in patients with HIV infection.
AB  - Progressive multifocal leukoencephalopathy (PML), a formerly rare disease, is
      estimated to occur in up to 5% of all patients with AIDS. The high prevalence of
      PML in AIDS patients currently enables a comprehensive evaluation of this
      disorder. We evaluated the clinical and radiographic features of PML in a large
      cohort of AIDS patients identified by retrospective chart review from 1981 to
      1994. Two hundred and five patients were diagnosed with PML of which 154 met the
      inclusion criteria. Seventy-two (47%) were pathologically confirmed and the
      remaining 82 (53%) met clinical and radiographic criteria. There was a 12-fold
      increase in the frequency of PML between 1981-1984 and 1991-1994. PML affected
      136 men and 18 women with AIDS. Eighty-four percent of cases were 20-50 years old
      (range 5 to 68 years). The most common AIDS risk factors were homosexuality (57%)
      among men and heterosexual transmission (28%) and intravenous drug abuse (28%)
      among women. In 27% of patients, PML heralded AIDS. Common manifestations
      included weakness, gait abnormalities, speech disturbance, cognitive disorders,
      headache, and visual impairment. The CD4 lymphocyte counts exceeded 200 cells in
      11% at the time of presentation. Involvement of posterior fossa structures was
      evident in 48% of cranial magnetic resonance imaging (MRI) studies, but in only
      11% of computed tomographies (CT) of the brain. Contrast enhancement, typically
      faint and peripheral, was seen in 10% of CT scans and 15% of MRIs. The median
      survival was 6 months and survival exceeded 1 year in 9%. PML is no longer a rare
      disease. It often heralds AIDS and may occur in the absence of significant
      decline in CD4 lymphocytes. Survival is generally poor, although prolonged
      survival beyond 1 year is not unusual.

PMID- 9531013
TI  - HIV decreases glutamate transport in SK-N-MC neuroblastoma cells.
AB  - Autopsy studies of patients with AIDS dementia have shown neuronal loss
      consistent with a neurotoxic component of this disease. In vitro studies suggest
      that viral products or cytokines from HIV-infected macrophages (Mphi) may
      modulate or directly mediate excitotoxic cell death of neurons. Mphi
      differentiated from peripheral mononuclear blood cultures were infected with HIV,
      and conditioned media (CM) were harvested from these cultures. Exposure of SK-N
      MC (neuroblastoma) cells to CM from HIV-infected Mphi for 4, 24 or > or = 48 h
      resulted in a mean suppression of 12-34% of the glutamate transport Vmax with no
      appreciable change in transport Km. An astrocytoma tumor cell, U373MG, showed
      similar CM-mediated glutamate uptake suppression. Changes were evident in total
      and Na+-dependent glutamate uptake, with significantly more suppression of Na+
      dependent uptake. Similar effects were seen with the nonmetabolizable transporter
      agonist D-aspartate, indicating that the effect was on transport and not
      metabolism. No suppression was seen with CM from uninfected Mphi or Mphi infected
      with heat-inactivated HIV. The magnitude of uptake suppression was not correlated
      with CM p24 values, and removal of CM virions by ultracentrifugation and
      immunoprecipitation did not alter the uptake-suppressive properties of infected
      Mphi CM. Uptake suppression was seen when Mphi were infected with Mphi-tropic
      strains HIV(SF162), HIV(JR-CSF), HIV(NFN-SX) and a Mphi-tropic patient isolate,
      but not the lymphotropic strain HIV(LAI). HIV-infected Mphi may produce
      substances which suppress neuronal and glial glutamate neurotransmitter uptake,
      resulting in higher extracellular glutamate levels and leading possibly to
      deficits in cell signaling and neurotoxicity.

PMID- 9531014
TI  - HIV-1 strain-associated variability in infection of primary neuroglia.
AB  - Qualitative differences among strains of Human Immunodeficiency Virus type 1 (HIV
      1) may influence viral infectivity for cells of the central nervous system (CNS)
      and determine or at least significantly influence the neuropathogenesis of brain
      infection. In this study, we compared infectivity for these cells in vitro among
      several different laboratory-adapted HIV-1 strains differing in cellular tropism.
      These strains included three lymphotropic strains (SF2, NL4-3, and SG3.1), two
      macrophage-tropic strains (SF128A, SF162), and one brain-derived strain (YU2). In
      microglia, macrophage-tropic strain SF128A established productive infection while
      the lymphotropic strain SF2 did not. In infected astrocytes, all HIV-1 strains
      transiently produced variable and much lower levels of p24 antigen. Viral DNA env
      or tat gene sequences were amplified from infected astrocytes; the amplified
      signals varied among HIV-1 strains, but the strongest viral DNA signals were
      obtained from cells infected by the lymphotropic strains SF2 and SG3.1.
      Transfection of astrocytes with infectious HIV-1 proviral DNA clones confirmed
      the observation that HIV-1 strains differ in their ability to replicate in
      astrocytes. Transfection revealed post-entry blocks to replication by macrophage
      tropic proviruses pSF128A and pSF162. However, cytomegalovirus (CMV)
      superinfection of transfected astrocytes enhanced p24 production by lymphotropic
      HIV-1 proviruses twofold and stimulated p24 production by the otherwise inactive
      macrophage-tropic proviruses. This study demonstrates the spectrum of HIV-1
      strain-associated variation in infectivity for neuroglia, and suggests, in
      addition, that herpesviral factors or viral-induced cellular factors may
      stimulate HIV-1 infection in astrocytes and expand the neural cell tropism of
      certain HIV-1 strains.

PMID- 9531015
TI  - CSF, plasma viral load and HIV associated dementia.
AB  - Plasma viral burden has proven valuable in predicting the future course of
      systemic HIV related disease and the response to treatment. It is not known
      whether plasma or cerebrospinal fluid (CSF) viral burden can be used to predict
      onset of or response to treatment of nervous system disease. We propose a model
      of viral load mediated neurotoxicity underlying peripheral and central HIV
      associated neurological disease. The objective of this preliminary study was to
      assess the relationship of HIV associated neurological disease to quantitative
      viral load in plasma and CSF. 47 subjects (HIV- = 10, HIV+ = 37) participated in
      the study. Plasma and CSF samples were collected within a 3 h window. RT-PCR
      (Roche Amplicor Monitor) was utilized to assess HIV-1 RNA viral load in both
      plasma and cell free (centrifuged) CSF. Subjects underwent concurrent
      comprehensive neurological and neuropsychological evaluations. In general,
      systemic viral load, as measured in plasma, was greater than that found in cell
      free CSF. Cell free CSF HIV RNA viral load was significantly correlated with
      neurological dysfunction, whereas plasma viral load was not. The sole subject
      with an elevated CSF viral load (> 5 Log 10), had HIV associated dementia (HAD)
      on clinical examination.

PMID- 9531016
TI  - Sustained cognitive decline in HIV infection: relationship to CD4+ cell count,
      plasma viremia and p24 antigenemia.
AB  - To determine the clinical and virological correlates of neuropsychological test
      performance decline in HIV infection, we measured viral burden in blood in 272
      HIV-seropositive men without dementia in the Baltimore arm of the Multicenter
      AIDS Cohort Study (MACS). These measures were then related to neuropsychological
      (NP) decline, defined as a decline relative to prior best performance of 2.0
      standard deviations or more on one or more neuropsychological tests. A short
      battery of NP tests (Mini-Screen Battery) was administered to all 272 men. NP
      test performance decline was identified in 53/272 (19.5%) of participants on the
      Mini-Screen Battery. Follow-up NP data were available for 204 participants who
      had undergone the Mini-Screen. The frequency of sustained NP test performance
      decline was 7.8% for the Mini-Screen Battery. A lower CD4+ cell count was weakly
      associated with sustained NP test performance decline. After adjustment for CD4+
      cell count, hemoglobin, body mass index, and presence of AIDS, none of the viral
      burden measures (p24 antigenemia, plasma viremia, quantitative culture)
      correlated with sustained NP test performance decline. We conclude that these
      measures of blood HIV viral burden are not markers for NP decline, but that a
      lower CD4+ cell count is.

PMID- 9531017
TI  - Toxicity and neuronal infection of a HSV-1 ICP34.5 mutant in nude mice.
AB  - HSV-1 mutants in the RL-1 gene encoding the ICP34.5 protein have been
      demonstrated to have diminished neurovirulence in brain yet replicate as
      efficiently as parental virus in transformed tissue culture cells. Thus they have
      been proposed as candidates viruses for human brain tumor therapies. Evaluation
      of their replicative properties and pathogenesis within the nervous system has
      been limited. As most patients undergoing therapies for brain tumors are likely
      to be immunocompromised, it will be important to understand the pathogenesis of
      these viruses in immunocompromised hosts. To this end, the lateral ventricle of
      nude mice was injected with high (2.5 x 10(7) PFU), medium (10(5) PFU), or low
      dose (10(3) PFU) HSV-1 variant-1716, which has a deletion in the RL-1 gene. Ten
      of 10 mice died within 2-3 days following the high titer infection. Six of 19
      animals with medium titer infection died within 9 days, and viral antigens were
      seen in ependymal cells as well as neurons within the brainstem and thalamus.
      Although only two of 19 animals became moribund 18 days after medium titer viral
      infection, many neocortical and hippocampal neurons were positive for HSV-1
      antigens. However, plaque-purified viral isolates recovered from brain
      homogenates of these animals demonstrated no increase in pathogenicity. Nine of
      20 animals died following low dose infection; six of these animals, from which
      tissue was analyzed, all had many HSV antigen-positive neurons in the neocortex
      and hippocampus. These data imply that if this type of virus is used for human
      brain tumor therapy immunosuppressed patients may suffer from significant viral
      pathogenesis outside the tumor.

PMID- 9531018
TI  - Variations of HSV-1 glycoprotein B in human herpes simplex encephalitis.
AB  - The factors which cause herpes simplex encephalitis (HSE) to occur among herpes
      simplex virus type 1 (HSV-1) infected humans are not understood. In experimental
      models, HSV-1 neuroinvasiveness is influenced by amino acid changes in HSV
      glycoproteins D (gD) or B (gB), which are essential to the virus infectivity and
      to the induction of host immune responses. To test the possible involvement of
      these glycoproteins in human HSE, we compared CSF-derived sequences of these
      genes with those obtained from peripheral HSV-1 isolates. We have previously
      shown the conservation of gD in 10 HSE samples. Here, we show that the functional
      domains of gB involved in cell penetration and cell fusion, and the major
      antigenic domains D2a, D2b and Dd5a were highly conserved. In the gB amino
      terminal domain, we distinguished several alleles that were common to HSE and
      peripheral isolates, and identified in only three out of fifteen HSE cases, a
      variation that was not encountered in 20 control strains. Overall, there were no
      striking differences between peripheral and HSE gBs. These results suggest that
      gB alone may not be responsible for neuroinvasiveness nor human
      neuropathogenicity.

PMID- 9531019
TI  - Infection characteristics of rabies virus variants with deletion or insertion in
      the pseudogene sequence.
AB  - We investigated the infection characteristics of recombinant rabies virus
      variants modified in the pseudogene sequence. Infection of neuronal cell lines by
      the SAD W9 and SAD V* variants (respectively with deletion or insertion in this
      sequence) showed no significant differences as compared to the parental strain,
      the attenuated strain SAD B19, in infection characteristics such as number of
      infected cells or viral yield. The inoculation of mice by these variants resulted
      in similar infection patterns and pathogenicity. Stereotaxic inoculation of the
      different variants into the rat striatum showed that deletion or insertion did
      not affect the axonal virus spread, nor did insertion of a complete additional
      transcription unit, that could be expressed in the areas connected to the
      inoculation site. These results show that the pseudogene sequence is not involved
      in viral spread and pathogenicity and confirm the availability of this domain for
      targeting and expression of foreign genes into neurons.

PMID- 9531020
TI  - Diagnosis and clinical management of neurological disorders caused by
      cytomegalovirus in AIDS patients. European Union Concerted Action on Virus
      Meningitis and Encephalitis.
AB  - Cytomegalovirus (CMV) infections are common and severe complications of HIV
      infection. The virus involves the nervous system, causing encephalitis,
      polyradiculomyelitis and peripheral neuropathies. Due to their limited
      sensitivity, traditional virological approaches, such as virus isolation or
      antigen detection in the CSF are useful only in limited instances, e.g. CMV
      polyradiculopathy. The aetiological diagnosis of these disorders relies on the
      analysis of cerebrospinal fluid by PCR and quantitative PCR may be important to
      establish the extent of CNS lesions and to monitor the efficacy of antiviral
      treatments. CMV is susceptible to various antivirals, including ganciclovir,
      foscarnet and cidofovir. CMV infections of the nervous system, in particular
      encephalitis, however, show only a poor response to standard treatments. Drug
      combination treatments i.e. ganciclovir plus foscarnet, are currently under
      evaluation in clinical trials.

PMID- 9531021
TI  - Progress toward elimination of measles from the Americas.
AB  - In 1994, the Pan American Health Organization (PAHO) established the goal of
      eliminating measles from the Western Hemisphere by 2000. To reach this goal, PAHO
      developed a measles-elimination strategy that includes three vaccination
      components ("catch-up," "keep-up," and "follow-up") and integrated epidemiologic
      and laboratory surveillance. The aim of the strategy is to achieve and maintain
      high levels of measles immunity among infants and children and detect all chains
      of transmission of measles virus through careful surveillance. This report
      updates measles surveillance data through February 1998 and summarizes the impact
      of elimination strategies on measles in the Americas.

PMID- 9531022
TI  - Suicide among black youths--United States, 1980-1995.
AB  - Although black youths have historically had lower suicide rates than have whites,
      during 1980-1995, the suicide rate for black youths aged 10-19 years increased
      from 2.1 to 4.5 per 100,000 population. As of 1995, suicide was the third leading
      cause of death among blacks aged 15-19 years, and high school-aged blacks were as
      likely as whites to attempt suicide. This report summarizes trends in suicide
      among blacks aged 10-19 years in the United States during 1980-1995 and indicates
      that suicidal behavior among all youths has increased; however, rates for black
      youths have increased more, and the gap between rates for black and white youths
      has narrowed.

PMID- 9531023
TI  - Update: influenza activity--United States, 1997-98 season.
AB  - In collaboration with the World Health Organization (WHO), its collaborating
      laboratories, and state and local health departments, CDC conducts surveillance
      to monitor influenza activity and to detect antigenic changes in the circulating
      strains of influenza viruses. This report summarizes influenza surveillance in
      the United States from September 28, 1997, through March 7, 1998, and presents
      reports of outbreaks in long-term care facilities (LTCFs) in three states and at
      a military base. The findings indicate that this season has been dominated by
      influenza A(H3N2) viruses and characterized by a sustained elevation in pneumonia
      and influenza (P&I)-related deaths.

PMID- 9531024
TI  - Factor VIII and von Willebrand factor.

PMID- 9531025
TI  - Molecular analyses of the platelet glycoprotein Ib-IX-V receptor.

PMID- 9531026
TI  - Novel deletion and insertion mutations cause splicing defects, leading to severe
      reduction in mRNA levels of the A subunit in severe factor XIII deficiency.
AB  - In order to explore molecular mechanisms for factor XIII deficiency, a patient
      (Nagoya I) was examined at the DNA and RNA levels. Nucleotide sequence analysis
      of the patient's DNA amplified by PCR revealed that he had a 20 bp deletion at
      the boundary of exon I/intron A, and an insertion of T in the invariant GT
      dinucleotide at the splicing donor site of exon IV/intron D. The presence of
      these heterozygous mutations was confirmed by restriction digestion of the
      amplified fragments of the proband and his parents. RT-PCR analysis demonstrated
      that only one kind of mRNA without exon IV was detected in Nagoya I, although its
      level was greatly reduced to less than 5% of normal. The other detective allele
      of the A subunit gene containing the 20 bp deletion was not detected. Thus, both
      mutations impaired normal processing of mRNA for the A subunit, resulting in his
      severe factor XIII deficiency.

PMID- 9531027
TI  - Factor X Nagoya 1 and Nagoya 2: a CRM- factor X deficiency and a dysfunctional
      CRM+ factor X deficiency characterized by substitution of Arg306 by Cys and of
      Gly366 by Ser, respectively.
AB  - We have identified, in two unrelated patients, factor X deficiency that we have
      designated factor X Nagoya 1 and Nagoya 2, respectively. The proband with factor
      X Nagoya 1 showed factor X activity level of 3% and factor X antigen level < 10%
      of the normal control value. All the exons and intron/exon junctions of the
      factor X gene were studied using a strategy combining polymerase chain reaction
      (PCR) amplification and nonradioactive single-strand conformational polymorphism
      (SSCP) analysis. Exon 8 containing DNA fragment of the proband with factor X
      Nagoya 1 showed aberrant migration on SSCP analysis. All exon-containing DNA
      fragments amplified by PCR were sequenced, and we identified a C-to-T
      substitution in exon 8 in the human factor X gene of the proband, which results
      in the replacement of Arg306 by Cys. This genetic defect has been transmitted
      from her father, and her sister also carried the same mutation; both showed
      almost half the normal levels of both factor X activity and antigen. The
      coordinates of human factor Xa indicated that Arg306 in the catalytic domain is
      positioned at the beginning of the alpha-helix near the second EFG-like domain.
      The substitution for Arg of Cys has been supposed to cause the destruction of
      local alpha-helix formation, possibly leading to the secretion problem. The
      proband with dysfunctional factor X Nagoya 2 was characterized by factor X
      activity level of 34% with normal factor X antigen level of 80%. We identified
      one substitution of G for A in exon 8 in the human factor X gene of the proband,
      which results in the replacement of Gly366 by Ser. As the Gly366 is positioned at
      the primary substrate binding pocket. the replacement of Gly with Ser would cause
      a defect of substrate binding, leading to the loss of enzymatic activity.

PMID- 9531028
TI  - Low-molecular weight heparin reduces the generation and activity of thrombin in
      unstable coronary artery disease.
AB  - Unstable coronary artery disease (UCAD) is associated with an increased risk of
      further coronary events. In the FRISC study, the risk was decreased during
      treatment with a high, twice-daily, dose of dalteparin, a low-molecular-weight
      heparin. However, lowering the dose resulted in raised risk of recurrences. To
      investigate the underlying pathophysiology, the thrombin generation and activity
      in patients with UCAD randomized to a 6-week placebo-controlled treatment with
      dalteparin were evaluated. Plasma prothrombin fragment 1+2 (F1+2) (n = 342),
      thrombin-antithrombin complex (TAT) (n = 186) and soluble fibrin (SF) (n = 298)
      were analyzed before and during treatment with dalteparin/placebo administered
      subcutaneously, 120 IU/kg bw twice daily for 5-8 days and 7.500 IU once daily the
      following 35-40 days. High-dose treatment with dalteparin resulted in
      significantly reduced levels of all coagulation markers, demonstrating diminished
      thrombin generation and activity. When reducing the dalteparin dose, plasma TAT
      and SF remained low, indicating minimal fibrin formation. However, F1+2 increased
      during this period. though the level at day 45 was still lower than in the
      placebo group. In the placebo group elevated thrombin generation and activity
      persisted during the entire period. In conclusion, high-dose treatment with
      dalteparin twice daily resulted in significantly reduced thrombin generation and
      activity. However, after changing to a lower, once-daily dose, the treatment was
      not sufficient in preventing a return to a procoagulable state. These changes of
      the coagulation activity might explain the changes in event rate observed during
      dalteparin treatment.

PMID- 9531029
TI  - Elevated tissue factor and tissue factor pathway inhibitor circulating levels in
      ischaemic heart disease patients.
AB  - Several studies have shown that thrombosis and inflammation play an important
      role in the pathogenesis of Ischaemic Heart Disease (IHD). In particular, Tissue
      Factor (TF) is responsible for the thrombogenicity of the atherosclerotic plaque
      and plays a key role in triggering thrombin generation. The aim of this study was
      to evaluate the TF/Tissue Factor Pathway Inhibitor (TFPI) system in patients with
      IHD. We have studied 55 patients with IHD and not on heparin [18 with unstable
      angina (UA), 24 with effort angina (EA) and 13 with previous myocardial
      infarction (MI)] and 48 sex- and age-matched healthy volunteers, by measuring
      plasma levels of TF, TFPI, Prothrombin Fragment 1-2 (F1+2), and Thrombin
      Antithrombin Complexes (TAT). TF plasma levels in IHD patients (median 215.4
      pg/ml; range 72.6 to 834.3 pg/ml) were significantly (p<0.001) higher than those
      found in control subjects (median 142.5 pg/ml; range 28.0-255.3 pg/ml).
      Similarly, TFPI plasma levels in IHD patients were significantly higher (median
      129.0 ng/ml; range 30.3-316.8 ng/ml; p<0.001) than those found in control
      subjects (median 60.4 ng/ml; range 20.8-151.3 ng/ml). UA patients showed higher
      amounts of TF and TFPI plasma levels (TF median 255.6 pg/ml; range 148.8-834.3
      pg/ml; TFPI median 137.7 ng/ml; range 38.3-316.8 ng/ml) than patients with EA (TF
      median 182.0 pg/ml; range 72.6-380.0 pg/ml; TFPI median 115.2 ng/ml; range 47.0
      196.8 ng/ml) and MI (TF median 213.9 pg/ml; range 125.0 to 341.9 pg/ml; TFPI
      median 130.5 ng/ml; range 94.0-207.8 ng/ml). Similar levels of TF and TFPI were
      found in patients with mono- or bivasal coronary lesions. A positive correlation
      was observed between TF and TFPI plasma levels (r = 0.57, p<0.001). Excess
      thrombin formation in patients with IHD was documented by TAT (median 5.2
      microg/l; range 1.7-21.0 microg/l) and F1+2 levels (median 1.4 nmol/l; range 0.6
      to 6.2 nmol/l) both significantly higher (p<0.001) than those found in control
      subjects (TAT median 2.3 microg/l; range 1.4-4.2 microg/l; F1+2 median 0.7
      nmol/l; range 0.3-1.3 nmol/l). As in other conditions associated with cell
      mediated clotting activation (cancer and DIC), also in IHD high levels of
      circulating TF are present. Endothelial cells and monocytes are the possible
      common source of TF and TFPI. The blood clotting activation observed in these
      patients may be related to elevated TF circulating levels not sufficiently
      inhibited by the elevated TFPI plasma levels present.

PMID- 9531030
TI  - Clinical utility of prothrombin fragment 1+2, thrombin antithrombin III complexes
      and D-dimer measurements in the diagnosis of deep vein thrombosis following total
      hip replacement.
AB  - BACKGROUND: Measurements of prothrombin fragment 1+2 (F1+2), thrombin
      antithrombin III complexes (TAT) and D-dimer plasma levels have been proposed as
      non-invasive screening tests to exclude postoperative deep venous thrombosis
      (DVT). We investigated the diagnostic efficacy of these coagulation activation
      markers to rule out postoperative DVT in patients undergoing hip surgery under
      antithrombotic prophylaxis. METHODS: In this substudy of a randomized double
      blind thrombosis prophylaxis trial comparing three doses of desirudin (10, 15 or
      20 mg b.i.d.) with unfractionated heparin (5000 IU t.i.d.) we used ELISA
      procedures to measure F1+2, TAT and D-dimer in 159 patients undergoing total hip
      replacement at baseline (day 0) and on postoperative days 1, 3 and 6. Bilateral
      venography was performed in all cases 8-11 days after surgery. RESULTS: For the
      F1+2 assay sensitivity ranged from 73 to 83% in the three postoperative days
      investigated, and negative predictive value (NPV) from 68 to 74%. For TAT and D
      dimer sensitivity ranged from 71 to 73% and from 71 to 83% and NPV from 61 to 65%
      and from 61 to 74% respectively. INTERPRETATION: In terms of sensitivity and NPV
      F1+2 and D-dimer are equivalent and are superior to TAT. However, their accuracy
      is too low to rule out the presence of DVT after hip surgery under antithrombotic
      prophylaxis.

PMID- 9531031
TI  - Factor V Leiden and fatal pulmonary embolism.
AB  - To investigate whether the factor V Leiden mutation increases the risk of fatal
      pulmonary emboli, we determined the presence of the factor V Leiden mutation in
      pathology material from two series of autopsies of patients from the Leiden
      University Hospital, The Netherlands. The first series consisted of consecutive
      autopsies in which pulmonary emboli were mentioned in the autopsy report; most
      patients of this series had major underlying disease. The second series consisted
      of autopsies in patients younger than age 70 in which pulmonary emboli were the
      sole cause of death and no major acquired risk factor for venous thrombosis was
      present. Extraction of DNA was done on newly prepared tissue from archival
      paraffin blocks. In the first series, the presence of factor V Leiden was
      determined in 44 patients, 1 of whom carried the mutation (2.3 percent; 95%
      confidence interval 0.06 to 12.0 percent). This prevalence is not different from
      the general population prevalence in The Netherlands. In the second series,
      factor V Leiden could be determined in 30 patients of whom 3 carried the mutation
      (10 percent; 95% confidence interval 2. to 26.5 percent), which would lead to a
      threefold relative risk. A large number of patients with diverse psychiatric
      diagnoses was present in the second series (eleven). We conclude that in the
      presence of severe illness, the factor V Leiden mutation plays no additional role
      in the development of pulmonary emboli. The relative risk of the very rare fatal
      pulmonary embolus that is the sole cause of death might also be less than the
      relative risk for deep-vein thrombosis in carriers of the factor V Leiden
      mutation.

PMID- 9531032
TI  - Feasibility study of catheter-directed thrombolysis with recombinant
      staphylokinase in deep venous thrombosis.
AB  - The feasibility of catheter-directed thrombolysis with recombinant staphylokinase
      was evaluated in six selected patients with deep vein thrombosis. The patients
      underwent intrathrombus infusion of recombinant staphylokinase (2 mg bolus
      followed by a continuous infusion of 1 mg/h). Heparin was given via the catheter
      as a bolus (5000 U) and as a continuous infusion (1000 U/h). Complete lysis was
      obtained in five patients and partial lysis in one patient. Complications
      consisted of minor bleeding in four subjects. Symptomatic reocclusion occurred in
      one. Debulking of the thrombus mass by a high speed rotating impeller (n = 1) and
      stenting (n = 3) were used as additional interventions. An underlying anatomical
      abnormality was present in two patients. Long term follow up revealed normal
      patency in all patients and normal valve function in four patients. Symptomatic
      venous insufficiency with valve dysfunction was present in the two with a second
      thrombotic episode. Thus catheter-directed infusion of recombinant staphylokinase
      in patients with deep vein thrombosis appears feasible and may be associated with
      a high frequency of thrombolysis. Larger studies to define the clinical benefit
      of this treatment appear to be warranted.

PMID- 9531033
TI  - Platelet cNOS activity is reduced in patients with IDDM and NIDDM.
AB  - Several studies in vitro and in vivo suggest that the nitric oxide (NO)
      production is impaired in diabetes mellitus. Reduced levels of NO could
      contribute to vascular alteration facilitating platelet-vascular wall
      interaction, adhesion of monocytes to endothelium, vascular smooth muscle
      proliferation and by decreasing endothelium-dependent vasodilation. In this study
      we evaluated the activity of the constitutive nitric oxide synthase (cNOS) in
      platelets of patients with insulin-dependent diabetes mellitus (IDDM) and with
      non-insulin-dependent diabetes mellitus (NIDDM). When compared to that of normal
      subjects, cNOS activity is significantly lower in patients with IDDM and with
      NIDDM (1.57 +/- 0.25 vs. 0.66 +/- 0.10 fmol/min/10(9) PLTs and 1.57 +/- 0.25 vs.
      0.67 +/- 0.08, respectively; p<0.005). These data demonstrate that the platelet
      cNOS activity is decreased in diabetes mellitus.

PMID- 9531034
TI  - Importance of the FcgammaRIIa-Arg/His-131 polymorphism in heparin-induced
      thrombocytopenia diagnosis.
AB  - Heparin-induced thrombocytopenia (HIT) involves heparin-dependent antibodies
      which induce platelet activation. In the present study, we searched for a
      relationship between the polymorphism of the Fc receptor (FcgammaRIIa) and the
      development of HIT. In this purpose, all the donors were genotyped for their
      FcgammaRIIA and HIT patients were selected on the basis of at least one positive
      answer by 14C-serotonin release assay (SRA). The frequency distribution of the
      FcgammaRIIa polymorphism in the HIT patient group was similar to that observed in
      the healthy control group. Moreover, a statistical analysis taking into account
      our results and those of 3 previously published studies, suggested at most only a
      weak association between HIT and the FcgammaRIIa-131 polymorphism. Laboratory
      tests used to diagnose HIT rely on the activation of normal donor platelets but
      fail to detect every HIT positive patient. We determined the role of FcgammaRIIa
      131 polymorphism on the reactivity of control platelets to HIT plasmas. When
      control platelet FcgammaRIIa-131 was of Arg/Arg form, only 47% of the HIT plasmas
      were positive by SRA, compared to 81% and 74% for His/His or His/Arg forms,
      respectively. We also compared the level of anti PF4/heparin antibodies in the
      HIT plasmas with the response obtained by SRA. The mean anti PF4/heparin
      antibodies level in HIT plasma was significantly lower in negative SRA than in
      positive tests when using control platelets from FcgammaRIIa-Arg/Arg 131 and
      heterozygous donors. Thus, the variability of control platelets to respond to HIT
      plasmas in the SRA test is related to both the FcgammaRIIa-131 polymorphism, and
      to the amount of anti PF4/heparin antibodies.

PMID- 9531035
TI  - Regulation of monocyte tissue factor activity by allogeneic and xenogeneic
      endothelial cells.
AB  - The regulation of tissue factor (TF) activity by the cell associated tissue
      factor pathway inhibitor (TFPI) during monocyte (Mo) and endothelial cell (EC)
      interactions is not fully understood. This report describes co-ordinate induction
      of TF antigen (TF-Ag) and membrane-associated TFPI-Ag on human Mo following
      coculture with human aortic (HAEC) or porcine aortic EC (PAEC) or after
      stimulation with TNFalpha. We show that both allo- and xenogeneic EC induce human
      Mo-TF antigen in short-term culture. However, the TF activity of TNFalpha-primed
      Mo is suppressed when these cells are cocultured with HAEC [by 40.3 +/- 6.3%
      (p<0.02)] or PAEC [by 50.5 +/- 10.6% (p<0.001)]. Antibody (Ab) blocking studies
      confirm that TFPI is the principal anticoagulant associated with this suppression
      of TF-activity. Our data indicate that anti-TF activity originates, at least in
      part, from the activated human Mo in the coculture; additionally, specific
      generation of TFPI by Mo is observed under the xenogeneic culture conditions. As
      Mo associated TF, induced by allo- or xenogeneic EC interactions, is regulated by
      cell-associated TFPI, we propose that infiltrating Mo may modulate the thrombotic
      process at sites of vascular injury in association with both allo- and xenograft
      rejection.

PMID- 9531036
TI  - Lonomia obliqua caterpillar spicules trigger human blood coagulation via
      activation of factor X and prothrombin.
AB  - In southern Brazil, envenomation by larvae of the moth Lonomia obliqua (Walker)
      may result in blood clotting factor depletion, leading to disseminated
      intravascular coagulation with subsequent haemorrhage and acute renal failure
      which may prove fatal. We have examined the effect of a crude extract of spicules
      from these caterpillars on in vitro hemostasis. The extract alone did not
      aggregate platelets and had no detectable effect on purified fibrinogen,
      suggesting that extract induces clot formation by triggering activation of the
      clotting cascade. In agreement with the presence of thrombin-mediated activity,
      hirudin prevented clot formation. The extract was found to activate both
      prothrombin and factor X, suggesting that the depletion of blood clotting factors
      results from the steady activation of factor X and prothrombin. Heating and
      diisopropylfluorophosphate abolished the procoagulant activity of the extract,
      indicating that the active component involved is a protein that may belong to the
      serine protease family of enzymes. The ability of hirudin to inhibit this
      coagulant activity suggests that this inhibitor could be beneficial in the
      treatment of patients envenomed by L. obliqua caterpillars.

PMID- 9531037
TI  - Biochemical and pharmacological characterization of YM-60828, a newly synthesized
      and orally active inhibitor of human factor Xa.
AB  - YM-60828 was found to potently inhibit human factor Xa following oral
      administration. YM-60828 showed high affinity for factor Xa (Ki = 1.3 nM), but
      did not affect thrombin (Ki > 100 microM). YM-60828 doubled factor Xa clotting
      time, prothrombin time (PT) and activated partial thromboplastin time (APTT) at
      0.10, 0.21, 0.24 microM, respectively. Importantly, it did not prolong thrombin
      time at 100 microM. YM-60828 also inhibited factor Xa in the prothrombinase
      complex with an IC50 value of 7.7 nM. In addition to its anticoagulant activity,
      YM-60828 inhibited platelet aggregation induced by various agonists (IC50 = 3 to
      23 microM). Squirrel monkeys were used to study the ex vivo anticoagulant
      activity and pharmacokinetic properties of YM-60828. One hour after oral
      administration at 3 mg/kg, YM-60828 strongly prolonged PT and APTT by 4.8- and
      1.9-fold, respectively, and plasma concentration reached 788 +/- 167 ng/ml.
      Bioavailability was calculated to be 20.3%. These results strongly suggest that
      YM-60828 will be a valuable orally active and potent anticoagulant agent showing
      potential antithrombotic activity.

PMID- 9531038
TI  - Activation of the coagulant pathway in cigarette smokers.
AB  - The effects of chronic cigarette smoking on the coagulation system were examined
      in 2964 men aged 50 to 61 years and clinically free of cardiovascular disease.
      Factor VII activity (VIIc), factor VII antigen (VIIag), prothrombin fragment 1+2
      (F1.2), fibrinopeptide A (FPA) and fibrinogen were measured in all participants,
      and activated factor VII (VIIa), factor IX activation peptide (IX pep) and factor
      X activation peptide (X pep) in a large sub-sample. The levels of all indices
      except FPA differed significantly between non-smokers, ex-smokers and current
      smokers. After adjustment for other conventional cardiovascular risk factors,
      mean VIIc was raised slightly by 3% in ex-smokers and current smokers as compared
      with non-smokers, owing to increases in VIIa and VIIag. Plasma IX pep, X pep,
      F1.2 and fibrinogen concentration were highest in current smokers, intermediate
      in ex-smokers and lowest in non-smokers. These findings accord with the increased
      risk of arterial thrombosis in smokers.

PMID- 9531039
TI  - Thrombomodulin levels during normal pregnancy, at delivery and in the postpartum:
      comparison with tissue-type plasminogen activator and plasminogen activator
      inhibitor-1.
AB  - Some studies suggest that soluble thrombomodulin (TM) could be used as a marker
      of preeclampsia or eclampsia. However little is known about the sequential
      changes of TM during the course of normal pregnancy. Levels of TM were determined
      in 100 women with uneventful pregnancies. Samples (n = 394) were divided into
      five study intervals, three during pregnancy, one at delivery and one three days
      postpartum. As compared with TM levels (median 34.3 ng/ml, range 17.6-61) of a
      control group of 60 healthy non-pregnant women, TM levels were shown to increase
      throughout pregnancy, median (and range) values being respectively 38.5 (17.6
      72.7) from 11 to 20 weeks, 45.2 (22.6-75.2) from 21 to 30 weeks and 54.3 (25.1
      114.5) ng/ml from 31st week to delivery. One hour after delivery TM levels were
      still elevated and dropped three days postpartum to 40.5 (20.9-79.4) ng/ml. The
      increase of TM levels was correlated with those of tissue-type plasminogen
      activator and plasminogen activator inhibitor-1 antigens. The large overlap in TM
      levels between the study periods seems to preclude a clinical use of TM based on
      reference values from a control group. Our data suggest that it would be more
      appropriate to take into account TM baseline values in a given woman to examine
      her TM increase during pregnancy.

PMID- 9531040
TI  - Mutation at either Arg336 or Arg562 in factor VIII is insufficient for complete
      resistance to activated protein C (APC)-mediated inactivation: implications for
      the APC resistance test.
AB  - Activated protein C (APC)-mediated inactivation of factor VIII (FVIII) correlates
      with cleavage at either Arg336 and/or Arg562. To elucidate the APC cleavage
      requirements for inactivation of FVIII, APC cleavage site mutants in FVIII
      (R336I, R562K and R336I/R562K) were made by site-directed mutagenesis. Analysis
      of these FVIII mutants expressed in COS-1 monkey cells demonstrated the thrombin
      cleaved mutant R562K was resistant to APC cleavage at residue 562 but not at
      Arg336 and the thrombin cleaved mutant R3361 was mostly resistant to APC cleavage
      at residue 336, but was sensitive to APC cleavage at Arg562. The double mutant
      R336I/R562K was mostly resistant to cleavage at residue 336 and completely
      resistant to cleavage at residue 562. Thus, APC cleavage of FVIII does not
      require a specific order of cleavage at either residue. The functional
      inactivation by APC was studied using partially purified preparations of FVIII
      expressed in Chinese hamster ovary cells. Both single mutants were inactivated at
      similar rates but slower than wild-type FVIII, whereas the double mutant
      R336I/R562K was resistant to inactivation. The ability of a commercially
      available APC-resistance assay kit to detect APC resistant FVIII was tested by
      reconstituting FVIII deficient plasma with the APC resistant mutants. Only the
      R336I/R562K demonstrated a reduced APC-resistance ratio, indicating that this
      assay can not detect the single APC cleavage site mutant of FVIII. These results
      suggest that APC-mediated cleavage at either Arg336 or Arg562 partially
      inactivate FVIII.

PMID- 9531041
TI  - Standardization of the APC resistance test. Effects of normalization of results
      by means of pooled normal plasma.
AB  - Results for APC resistance tests are expressed as the ratio of the clotting time
      with and without APC (APC ratio). Normalization by dividing the patient's APC
      ratio by that of the pooled normal plasma (PNP) (n-APC ratio) was proposed to
      minimize between-lot reagent variability. To evaluate the merits of different
      expressions of the results, sets of 80 coded frozen plasmas from carriers (n =
      30), non-carriers (n = 30) of the FV:Q506 mutation and 10 copies each of two
      control plasmas were sent to 7 expert laboratories which were asked to assess APC
      resistance by their methods. Results were expressed as APC ratio and n-APC ratio
      by the local PNP and 2 common PNP (A and B). These contained plasmas from the
      same (n = 20) non-carriers. In PNP A, plasma from one non-carrier was replaced
      with that from one heterozygous carrier. The merits of different expression of
      results were judged by (i) within-laboratory reproducibility: (ii) discrimination
      of carriers from non-carriers: (iii) between-method comparability of results. The
      influence of FV:Q506 plasma in the preparation of PNP was also assessed.
      Reproducibility, generally good even with results expressed as APC ratio (median
      CV 4.6% and 3.0% for normal and abnormal control), was not changed by
      normalization. Discrimination did not change whatever the method of result
      expression. Between-method comparability of results was scarcely affected by
      normalization with the local PNP, whereas it was considerably improved after
      normalization with the common PNP, but only for the non-carriers. APC ratios for
      PNP A by all methods were significantly lower than those for PNP B. Thus, the
      presence of mutant FV in a proportion as low as 2.5% may reduce the APC ratio of
      the PNP.

PMID- 9531042
TI  - Sensitivity, specificity and predictive value of modified assays for activated
      protein C resistance in children.
AB  - Very little data is available assessing the clinical utility of coagulation-based
      APC resistance assays compared to DNA-based analysis for the factor V Leiden
      mutation in children. Therefore, the clinical utility of four aPTT-based assays
      for APC resistance was evaluated in 169 children, ages 3 months through 16 years.
      The prevalence of the Arg506 to Gln mutation was 7/169 (4.1%). Using cutoff
      points derived from the normal PCR-screened population (n = 162), two assays for
      APC resistance (APC-SR and n-APC-SR) gave poor concordance with the PCR assay
      (sensitivity 29% and 57%, respectively). Two modified assays (FDAPC-SR and n
      FDAPC-SR), in which patient plasma was prediluted 1:5 in factor V deficient
      plasma, gave excellent concordance (sensitivity 100%). The predictive value of a
      positive test was 0.25, 0.44, 1.00 and 0.88 for the APC-SR, n-APC-SR, FDAPC-SR
      and n-FDAPC-SR, respectively. The FDAPC-SR and n-FDAPC-SR tests gave excellent
      discrimination using cutoff values derived from the total population (n = 169)
      without regard to previous PCR screening results.

PMID- 9531043
TI  - Changes of prothrombin fragment 1+2 (F 1+2) as a function of increasing intensity
      of oral anticoagulation--considerations on the suitability of F 1+2 to monitor
      oral anticoagulant treatment.
AB  - Plasma F 1+2 levels, the activation peptide originating from the factor Xa
      mediated activation of prothrombin, increase in many clinical conditions
      associated with hypercoagulability and decrease in patients on oral anticoagulant
      treatment (OAT). However. the usefulness of F 1+2 measurement to monitor OAT has
      not yet been investigated in clinical studies. Before those studies are
      attempted, the plausibility of its implementation in the laboratory control of
      OAT should be evaluated. In this respect, a thorough investigation of the pattern
      of changes of F 1+2 as a function of increased intensity of anticoagulation
      expressed as International Normalized Ratio is essential. One hundred and thirty
      two patients on long-term warfarin treatment were recruited to cover 8 ranges of
      anticoagulation from < 1.5 to 9.0 INR. F 1+2 was measured in batch on frozen
      plasma and INR was determined on fresh plasma. The relationship of F 1+2 vs. INR
      showed a hyperbolic pattern with F 1+2 levels decreasing progressively and
      significantly as a function of increasing INR up to 3.0. A further decrease in F
      1+2 levels observed at INR up to 4.0 was not statistically significant. At INR
      greater than 4.0, F 1+2 reached a plateau, with mean levels not significantly
      different for patients at increasing INR up to 9.0. Since the risk of bleeding
      increases at INR greater than 4.5, our results suggest that F 1+2 is of little
      value to assess the hemorrhagic risk in patients on OAT.

PMID- 9531044
TI  - Transcriptional regulation of urokinase-type plasminogen activator receptor by
      cyclic AMP in PL-21 human myeloid leukemia cells: comparison with the regulation
      by phorbol myristate acetate.
AB  - We investigated the effect of dibutyryl cyclic AMP (Bt2-cAMP) on urokinase-type
      plasminogen activator receptor (uPAR) expression in human PL-21 myeloid leukemia
      cells and compared it with the effect of phorbol myristate acetate (PMA). Flow
      cytometric analysis clearly demonstrated that Bt2-cAMP and PMA both induced the
      cell surface expression of uPAR. Northern analysis and nuclear run-on assay
      revealed that cAMP and PMA activated the uPAR gene transcription and both
      additively increased the uPAR mRNA level. However, actinomycin-D decay experiment
      showed that PMA, but not cAMP, prolonged the uPAR mRNA half-life. Furthermore,
      inhibition of the ongoing protein synthesis with cycloheximide abrogated
      completely the PMA-induced uPAR mRNA accumulation but only partially the
      induction by PMA plus cAMP, whereas the induction by cAMP alone was rather
      amplified, indicating that the de novo protein synthesis is necessary in the
      induction by PMA but not in the induction by cAMP and that the cAMP pathway may
      be dominant in uPAR gene expression in the PL-21 cells as compared to the PMA
      pathway. These results suggest that cAMP induces the uPAR expression exclusively
      through activating the gene transcription in which a preexisting transcriptional
      factor may be involved, whereas PMA transcriptionally and posttranscriptionally
      regulates the uPAR gene expression.

PMID- 9531046
TI  - Sex differences in the determinants of fibrinolytic activity.
AB  - Impaired whole blood fibrinolytic activity (FA), measured by the dilute clot
      lysis time (DCLT), is associated with first episodes of ischaemic heart disease
      (IHD) in the Northwick Park Heart Study in men, especially under 55 years, and in
      women. In a community-based study to investigate possible determinants of the
      DCLT, and therefore to assess which fibrinolytic components might be predictors
      of first IHD events, we measured fibrinolytic variables in a sub-sample of 150
      healthy adults (73 males, 77 females) randomly selected from a single general
      practice. Most of the variance in DCLT (68% in men, 63% in women) was explained
      by tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor
      type-1 (PAI-1) activities. In multiple regression analysis there was a
      significant difference in the strength of the association of t-PA activity with
      DCLT in men compared to women (test for interaction p = 0.05), the association of
      t-PA activity with DCLT being significant in males but not in females. Plasma PAI
      1 activity was strongly associated with DCLT in both sexes. There was no
      independent association of DCLT with plasma fibrinogen, t-PA antigen, other
      fibrinolytic inhibitors, body mass index, serum lipids or C-reactive protein.
      Plasma PAI-1 activity in females and both t-PA and PAI-1 activities in males are
      the main determinants of whole blood FA measured by DCLT. It is therefore likely
      that these modulators of the plasma fibrinolytic system are associated with the
      onset of first clinical episodes of IHD. Elevated levels of t-PA antigen were
      positively associated with DCLT after adjustment for age and sex and therefore
      indicate impaired rather than enhanced FA. Further studies of the association of
      FA with risk of IHD should include not only "global" measures but also assessment
      of t-PA and PAI-1 activities, particularly as our results suggest that their
      associations with IHD may differ in men and women.

PMID- 9531045
TI  - Relation of urokinase-type plasminogen activator expression to presence and
      severity of atherosclerotic lesions in human coronary arteries.
AB  - Urokinase-type plasminogen activator (UPA) has been implicated in a broad
      spectrum of pathological processes - e.g. cell adhesion, migration and
      proliferation and matrix remodeling - that are considered important features of
      atherogenesis and plaque disruption. In this study, we have analyzed the content
      and expression of UPA in human coronary arteries and its relation to the presence
      and severity of atherosclerotic lesions. Segments of coronary arteries obtained
      from human heart explants (n = 15) were classified by the presence and types of
      atherosclerotic lesions. UPA was quantitatively determined in protein extracts of
      the intimal and medial layers. In situ hybridization and immunohistochemical
      analyses were performed on serial sections of representative tissue specimens.
      UPA was detected in the extracts as pro-UPA, UPA complexed to plasminogen
      activator inhibitor-1, or as otherwise inactive UPA antigen, but not in the
      active two-chain form. Both functional and total UPA were increased several-fold
      in extracts of advanced lesions, while the ratios of functional over total UPA
      showed the opposite trend suggesting enhanced UPA inactivation and turnover. UPA
      expression in early atherosclerotic lesions was particularly prominent in areas
      of proliferating SMCs in the abluminal part of the neointima, whereas in advanced
      lesions UPA was widely expressed in macrophage-rich areas adjacent to the rims
      and shoulder regions of the necrotic cores. The results strongly suggest a causal
      involvement of UPA in coronary atherogenesis and its clinical outcome.

PMID- 9531047
TI  - Enhancement of fibrinolysis by plactins: structure-activity relationship and
      effects in human U937 cells and in mice.
AB  - Plactin D, a cyclic pentapeptide [cyclo(-D-Val-L-Leu-D-Leu-L-Phe-D-Arg-)]
      produced by a fungal strain, enhances fibrinolytic activity (6). The present
      study deals with the structure-activity relationship of plactins and their
      effects in U937 cells and mice. The results obtained from 50 plactin D analogues
      with a single amino acid substitution demonstrated that the following
      substitutions were detrimental: the enantiomer for each of the five residues; a
      polar, an acidic or a basic residue for D-Val, L-Leu, D-Leu or L-Phe; a polar, a
      hydrophobic or an acidic residue for D-Arg. On the other hand, a compound with L
      Leu or L-Val in place of L-Phe was seven times as active as plactin D. These
      results suggest an essential role of a sterically restricted arrangement of four
      hydrophobic residues and the adjacent basic residue. The enhancement of
      fibrinolysis was dependent on plasma, ranging from 2- to 3-fold when U937 cells
      were incubated with 15-30 microM plactin D in the presence of 6-50% plasma, while
      no elevation was observed when cells were incubated in the absence of plasma.
      Plasminogen alone could not substitute for plasma. The plactin D effect was
      totally abolished by anti-urokinase IgG but not by anti-tissue plasminogen
      activator IgG. Plactin D caused a plasma-dependent, transient increase in the
      cellular urokinase activity. This urokinase activation may have accounted for the
      increased fibrinolytic activity of plactin D-treated U937 cells. Homogenates of
      the lung obtained from mice 0.5 to 2 h after intravenous plactin D (5 mg/kg)
      showed 2- to 3-fold increased levels of fibrinolytic activity, while activities
      of the brain, heart, liver, spleen, kidney and aorta were not significantly
      affected. In conclusion, plactin D enhances fibrinolysis both in cultured
      mammalian cells and in experimental animals.

PMID- 9531048
TI  - Identification of a functional epitope in plasminogen activator inhibitor-1, not
      localized in the reactive center loop.
AB  - Plasminogen activator inhibitor-1 (PAI-1) is unique among the serpins because of
      its conformational flexibility. Previously, we have characterized monoclonal
      antibodies that neutralize PAI-1 activity by switching the active, inhibitory
      pathway into the non-inhibitory substrate pathway (10). Here, we report the
      identification of the epitopes for two of these antibodies, i.e. MA-55F4C12 and
      MA-33H1 and apply this information to explain their functional effects. Using a
      random PAI-1 epitope library (11), phages displaying specific PAI-1 fragments
      were isolated after selective screening for binding onto the respective
      antibodies. Competition experiments with PAI-1 demonstrated that selected phages
      react with the antigen-binding site of the antibodies. Comparison of the
      sequences of the different overlapping inserts, encoding the PAI-1 epitope, with
      the PAI-1 cDNA sequence revealed that both epitopes, even though not identical,
      are located between amino acids Glu128 and Ala156 in the PAI-1 molecule. Analysis
      within the three-dimensional structure of PAI-1 showed that these residues
      completely cover helix F, which is localized close to the major beta-sheet A.
      This localization provides a rational basis for explaining the mechanism of PAI-1
      inactivation by both antibodies: upon binding of these antibodies to PAI-1, a
      stabilizing effect is induced on helix F resulting in a decrease of the kinetics
      of insertion of the reactive site loop into beta-sheet A during interaction with
      the target proteinase. This forms the molecular basis for the observed functional
      effects of these antibodies and fully explains why PAI-1, in the presence of
      these antibodies, has lost its inhibitory properties but remains succeptible to
      cleavage by its target proteinases. The identification and localization of these
      functionally important epitopes opens new perspectives for the development of
      pharmacological agents with PAI-1 modulating properties.

PMID- 9531049
TI  - Platelets and endothelial cells act in concert to delay thrombolysis--evidence
      from an in vitro model of the human occlusive thrombus.
AB  - The molecular and cellular mechanisms that over a period of hours render a human
      thrombus progressively resistant to fibrinolysis have been probed with a novel in
      vitro model. The kinetics of clot formation and fibrinolysis were monitored by
      laser light scattering with platelet-rich model thrombi contained in cylindrical
      flow chambers. In selected experiments, human umbilical vein endothelial cells
      were also cultured to confluence on the inner walls of these "glass blood
      vessels". Following an "aging" period (0.5, 2 or 4 h), each thrombus was gently
      perfused with a bolus of plasminogen/recombinant tissue plasminogen activator to
      induce fibrinolysis. Platelets delayed lysis of 2 h-aged thrombi by approximately
      70% and (non-stimulated) endothelial cells by approximately 30%, compared to cell
      free control clots. However, even greater lytic delays (approximately 260%)
      resulted when both vascular cells were present in the same 2 h-aged thrombus. In
      contrast, rapid lysis was consistently achieved with R298E,R299E t-PA, a
      genetically engineered plasminogen activator that is insensitive to inhibition by
      plasminogen activator inhibitor type 1. These observations suggest platelets and
      endothelial cells act in concert to enrich the fibrin scaffold of an aging human
      thrombus in plasminogen activator inhibitor. We propose that the presence of both
      platelets and endothelial cells may contribute to progressive thrombolytic
      resistance.

PMID- 9531050
TI  - Alboaggregins A and B. Structure and interaction with human platelets.
AB  - Viper venoms contain a variety of platelet binding proteins including those which
      bind to platelet GPIb/GPIX. Most of these proteins inhibit von Willebrand factor
      mediated platelet agglutination. Here we report the primary structures of unique
      members of this family, alboaggregins A and B, isolated from Trimeresurus
      albolabris, which have the ability to stimulate platelet agglutination and
      aggregation. Four chains of alboaggregin A and two chains of alboaggregin B share
      a high degree of homology and all cysteines in both alboaggregins are conserved.
      Both alboaggregins caused similar agglutination of fixed platelets. Alboaggregin
      A induced platelet aggregation and release reaction with EC50 = 10 and 30 nM,
      respectively, which is 20-fold lower than those for alboaggregin B. These
      observations suggest that the dimeric structure of alboaggregin B is sufficient
      to mediate its binding to GPIb and induce agglutination of platelets whereas
      aggregation and release reaction are significantly enhanced by tetrameric
      structure of alboaggregin A.

PMID- 9531051
TI  - Inhibition of rat platelet aggregation by mycalolide-B, a novel inhibitor of
      actin polymerization with a different mechanism of action from cytochalasin-D.
AB  - In vitro effects of mycalolide-B (MB), isolated from marine sponge, were
      investigated with regard to the activation of rat platelets. Collagen-induced
      platelet aggregation in platelet-rich plasma (PRP) was slightly but significantly
      potentiated by lower concentrations of MB (0.3 and 1 microM) but was inhibited by
      higher concentrations (3 and 10 microM). ADP-induced platelet aggregation in PRP
      was also significantly prevented by MB (1-10 microM). Potentiation of ADP-induced
      aggregation by MB (0.3 microM) was hardly observed. G-actin contents, determined
      by DNase I inhibition assay, were increased in resting washed platelets incubated
      with MB (3 microM). In contrast, cytochalasin-D (CD) at 3 microM slightly reduced
      G-actin contents in resting platelets. After platelet aggregation with collagen
      (3 microg/ml) or ADP (10 microM), G-actin contents in platelets were reduced,
      indicating de novo actin polymerization. MB (3 microM) and CD (3 microM)
      abolished both ADP (10 microM)- and collagen (3 microg/ml)-induced platelet
      aggregation and actin polymerization in washed platelets. MB (1-10 microM) had no
      effects on intracellular Ca2+ concentrations in ADP (10 microM)-stimulated
      platelets. [125I]-fibrinogen binding to activated platelets with ADP (10
      microM)(was inhibited by MB (0.3-3 microM) in a concentration-dependent manner.
      Thrombin-induced platelet-fibrin clot retraction was inhibited by MB (1 and 10
      microM). These results suggest that MB inhibits platelet activation by
      interfering with actin polymerization through a different mechanism of action
      from CD. MB may be a useful tool for studying the role of actin polymerization in
      various cells.

PMID- 9531052
TI  - Comparison of antiplatelet effects of two nitric oxide-donating agents, FR146801
      and FK409.
AB  - In the present study, we examined the antiplatelet effects of the two nitric
      oxide (NO)-donating agents, (+/-)-N-[(E)-4-ethyl-3-[(Z)-hydroxyimino]-6-methyl-5
      nitro-3-he ptenyl]-3-pyridinecarboxamide (FR146801). a more stable analog of
      FK409 ((+/-)-(E)-4-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenamide ), and FK409
      in in vitro and in vivo experiments. FR146801 and FK409 inhibited ADP- and
      collagen-induced platelet aggregation in human and rat platelet-rich plasma in a
      concentration-dependent manner, however, the inhibitory effect of FR146801 was
      weaker than that of FK409. In human washed platelets (WP), FR146801 and FK409
      inhibited collagen-induced platelet aggregation in a concentration-dependent
      manner. The inhibitory effects of FR146801 and FK409 on platelet aggregation were
      closely reflected by the increase in the intraplatelet cGMP level. This intensely
      suggests that the antiplatelet activities of FR146801 and FK409 are due to NO
      released from them. In the rat extracorporeal shunt model, FR146801 inhibited
      thrombus formation dose-dependently and its inhibition was significant at 10
      mg/kg, p.o. FK409 suppressed thrombus formation significantly at 1.0 mg/kg, p.o.,
      at which it induced significant hypotension, whereas FR146801 did not show any
      significant hypotensive effect even at 10 mg/kg, p.o. These results suggest that
      FR146801 has desirable antiplatelet effects both in vitro and in vivo and that
      its in vivo antiplatelet effect is more selective than its hypotensive effect,
      while FK409 does not show a selective antiplatelet effect in vivo.

PMID- 9531053
TI  - Inhibition of fibrinogen binding and surface recruitment of GpIIb/IIIa as dose
      dependent effects of the RGD-mimetic MK-852.
AB  - Conformational activation of platelet GpIIb/IIIa which is coupled to increased
      affinity for binding of soluble fibrinogen is an important step in platelet
      aggregation. Antibodies, peptides, and small molecules which antagonise
      fibrinogen binding, therefore, have been developed as a new class of potent anti
      aggregatory compounds. The binding of these artificial ligands, however, similar
      to fibrinogen binding may also stimulate platelet adhesion and degranulation.
      Therefore, in this study effects of MK-852, a cyclic hexapeptide based on the RGD
      template, on the platelet phenotype were analysed by whole blood flow cytometry.
      MK-852 already in the nanomolar range completely inhibited the surface binding of
      fibrinogen to ADP or TRAP-6 stimulated platelets. In the micromolar range, MK-852
      induced an up to four-fold increase of GpIIb/IIIa surface expression in the
      absence of increased P-selectin expression. In conclusion our results suggest
      that the selective surface recruitment of GpIIb/IIIa may be a side effect of
      exposure to RGD-analogues which occurs at concentrations well above inhibition of
      fibrinogen binding.

PMID- 9531054
TI  - Atrial natriuretic peptide inhibits the expression of tissue factor and
      plasminogen activator inhibitor 1 induced by angiotensin II in cultured rat
      aortic endothelial cells.
AB  - The pharmacological characteristics of atrial natriuretic peptide (ANP), such as
      natriuresis, vasodilation, or suppression of smooth muscle cell proliferation,
      are well investigated. However, this is the first study to report its role on
      blood coagulation and fibrinolysis mediated by vascular endothelial cells. In
      this study, the effects of ANP on the enhanced expression of tissue factor (TF)
      and plasminogen activator inhibitor 1 (PAI-1) by angiotensin II (Ang II) in
      cultured rat aortic endothelial cells (RAECs) were examined. The expressions of
      TF and PAI-1 mRNA were detected by northern blotting methods. The activities of
      TF on the surface of RAECs and PAI-1 in the culture media were measured by
      chromogenic assay. ANP suppressed mRNA expressions of TF and PAI-1 induced by Ang
      II in a concentration-dependent manner. This suppression was accompanied by the
      decreased activities of TF and PAI-1.

PMID- 9531055
TI  - Suppression of intimal hyperplasia by a 5-lipoxygenase inhibitor, MK-886: studies
      with a photochemical model of endothelial injury.
AB  - Intimal thickening is a major complication following percutaneous transluminal
      coronary angioplasty, which leads to restenosis and requires reoperation. We have
      investigated the effect of a 5-lipoxygenase inhibitor, MK-886, a leukotriene B4
      (LTB4) receptor antagonist, ONO-4057 or a LTC4 and LTD4 receptor antagonist, ONO
      1078, on intimal thickening. Photochemical reaction between green light and
      systemically administered Rose Bengal produced intimal thickening in the rat
      femoral artery. Each drug was administered orally, once a day for 7 days,
      starting just after the endothelial injury. Both MK-886 administration, 10 mg/kg,
      and ONO-4057 administration, 100 mg/kg, suppressed intimal thickening level
      examined three weeks after endothelial injury, while similarly administered ONO
      1078 did not. In cultured rat-derived smooth muscle cells, LTB4, an active
      metabolite of 5-lipoxygenase whose biosynthesis in air pouch exudate was
      suppressed by MK-886, stimulated cell migration. Based on these observations, the
      5-lipoxygenase may have a key role in intimal thickening via its metabolites such
      as LTB4.

PMID- 9531056
TI  - Phospholipase A2 modification enhances lipoprotein(a) binding to the
      subendothelial matrix.
AB  - Lipoprotein(a), Lp(a), is found in the extracellular matrix in atherosclerotic
      plaques, but with a different localization than LDL. A two-compartment system,
      with a monolayer of endothelial cells forming a barrier, was used to compare the
      transport, cell binding, and retention of Lp(a) and LDL into the subendothelial
      matrix. Baseline values for transport and retention of Lp(a) and LDL were not
      significantly different. Incubation with lipoprotein lipase or sphingomyelinase
      caused modest and similar increases in transport and retention of the two
      lipoproteins. In contrast, incubation with phospholipase A2 (PLA2) resulted in a
      marked (4-fold) increase in retention of Lp(a) on the subendothelial matrix, but
      a lesser (2-fold) increase in LDL retention. Moreover, PLA2 treatment of Lp(a)
      enhanced its binding to individual matrix proteins (fibronectin, laminin, or
      collagen) by 4-10 times above that of LDL. The enzymatic activity of PLA2 was
      responsible for its effect on Lp(a) binding. The lysine binding sites of Lp(a)
      contributed to the increased binding of PLA2-modified Lp(a) to the matrix, and
      the enhanced lysine binding functions of PLA2-modified Lp(a) was demonstrated by
      two independent approaches. Thus, PLA2 modification leads to enhanced
      interactions of lipoproteins with the extracellular matrix, and this effect is
      more pronounced with Lp(a).

PMID- 9531057
TI  - Tissue factor pathway inhibitor in tetracycline-induced pleuritis in rabbits.
AB  - Pleural fibrin deposition that promotes loculation and fibrosis after pleural
      injury is initiated by tissue factor (TF). In this study, we sought to determine
      if tissue factor pathway inhibitor (TFPI), an inhibitor of the TF-factor VIIa
      complex, was likewise expressed in tetracycline (TCN)-induced pleural injury and,
      if so, whether TFPI was locally elaborated. Pleural fluid TFPI activity
      approximated that of plasma by 24 h and doubled by 3 days after intrapleural TCN.
      By contrast, pleural fluid coagulation factors VII and V remained below plasma
      concentrations at these intervals. Immunohistochemical studies demonstrated TF,
      TFPI and fibrin localized in pleural and subpleural tissues and within
      intrapleural adhesions. TFPI activity and mRNA were also elaborated by rabbit
      pleural mesothelial cells and lung fibroblasts. TFPI is locally expressed and
      pleural fluid TFPI exceeds plasma levels during TCN-induced pleural injury.
      Resident cells as well as extravasation likely contribute to intrapleural TFPI.
      TFPI expression temporally and anatomically approximates that of TF and may limit
      TF-induced fibrin deposition in evolving TCN-induced pleuritis.

PMID- 9531058
TI  - Assessment of thrombin inhibitor efficacy in a novel rabbit model of simultaneous
      arterial and venous thrombosis.
AB  - The importance of thrombin in arterial and venous thrombosis renders thrombin
      inhibition an important therapeutic target. Identification of novel inhibitors
      requires an appropriate animal model. We modified a previously reported rat
      arterial thrombosis model to allow simultaneous assessment of the arterial and
      venous antithrombotic efficacies of heparin, hirudin, hirulog, a novel thrombin
      inhibitor H-(N-Me-D-Phe)-Pro-L-trans-4-aminocyclohexyl-Gly-[CO-CO]-NHCH3+ ++ (L
      370,518) and the factor Xa inhibitor tick anticoagulant peptide in rabbits.
      Thrombosis was induced through application of 70% ferric chloride to the femoral
      artery and jugular vein. Incidence of occlusion, thrombus weight, aPTT and plasma
      inhibitor concentrations were determined. Heparin was efficacious in preventing
      arterial and venous occlusive thrombosis but at a dose that profoundly elevated
      aPTT. On a molar dosing basis, the approximate order of potency of the thrombin
      and factor Xa inhibitors was similar in artery and vein: hirudin>tick
      anticoagulant peptide>hirulog> or =L-370,518. Data suggested that compounds
      tended to be more potent in preventing venous thrombosis than arterial. This
      thrombin-dependent model is an economical and efficient approach to arterial and
      venous antithrombotic efficacy screening that eliminates variabilities
      encountered when multiple model/multiple animal strategies are employed.

PMID- 9531059
TI  - Enhancement of tissue-type plasminogen activator-induced thrombolysis and
      prevention of reocclusion by combination with a humanized anti-glycoprotein
      IIb/IIIa monoclonal antibody, YM337, in a rhesus monkey model of coronary
      thrombosis.
AB  - We examined the effect of a humanized anti-glycoprotein IIb/IIIa monoclonal
      antibody, YM337, on thrombolysis with tissue-type plasminogen activator in a
      copper coil-induced coronary thrombosis model in rhesus monkeys. Fifty minutes
      after the formation of an occlusive thrombus, a test drug was administered by
      either i.v. bolus injection followed by continuous infusion (YM337, 0.25 mg/kg +
      1.5 microg/kg/min) or i.v. bolus injection (aspirin, 17 mg/kg). Sixty minutes
      after induction of the occlusive thrombus, thrombolysis was initiated with tPA at
      a total dose of 0.5 mg/kg intravenously administered over 60 min, with 10% given
      as an initial bolus. The median time to reperfusion was significantly shortened
      by YM337 [saline, 60 min (n = 5); aspirin, 45 min (n = 5); YM337, 30 min (n =
      5)]. The incidence of reocclusion was significantly decreased by YM337 (saline,
      4/4; aspirin, 5/5; YM337, 1/5), and the median time to reocclusion was
      significantly prolonged by YM337 [saline, 30 min (n = 4); aspirin, 30 min (n =
      5); YM337, 180 min (n = 5)]. YM337 significantly reduced the thrombus protein
      content at the end of experiment. ADP-induced platelet aggregation was completely
      inhibited by YM337. These results suggest that YM337 may be of clinical value as
      an adjunctive agent in thrombolytic therapy for patients with acute myocardial
      infarction.

PMID- 9531060
TI  - Snake venom fibrinogenolytic and fibrinolytic enzymes: an updated inventory.
      Registry of Exogenous Hemostatic Factors of the Scientific and Standardization
      Committee of the International Society on Thrombosis and Haemostasis.

PMID- 9531061
TI  - Thrombin-like enzymes from snake venoms: an updated inventory. Scientific and
      Standardization Committee's Registry of Exogenous Hemostatic Factors.

PMID- 9531062
TI  - High prevalence of factor V R506Q mutation in German thrombophilic and normal
      population.

PMID- 9531063
TI  - Prevalence of factor V(Q506) and prothrombin 20210 A mutations in an apparently
      healthy Icelandic population and patients suffering from venous thrombosis.

PMID- 9531064
TI  - Prevalence of the 677C to T mutation in the methylenetetrahydrofolate reductase
      gene in Italian patients with venous thrombotic disease.

PMID- 9531065
TI  - The effect of age and menopause on erythrocyte aggregation.

PMID- 9531066
TI  - The role of ABO blood groups in the incidence of deep vein thrombosis.

PMID- 9531067
TI  - Plasma levels of factor VIIa are very low in neonates and infants.

PMID- 9531068
TI  - Comparison of the E test with broth microdilution for antifungal susceptibility
      testing of yeasts.
AB  - The susceptibilities of 26 recent invasive clinical isolates to amphotericin B
      (AMP), 5-flucytosine (5FC), fluconazole (FLU) and itraconazole (ITR) were
      determined by a broth microdilution modification of the NCCLS M27P method and
      also by E test. Using breakpoint criteria each result was classified as either
      sensitive (S), intermediate (I) or resistant (R). Taking the optical density
      (OD)80 as the standard, the results were further classified into major (M) or
      minor (m) errors. E test: AMP = 0M 0m, 5FC = 0M 5m, FLU = 1M 12m, ITR = 1M 5m
      errors. Minimal inhibitory concentrations (MIC): AMP = 0M 2m, 5FC = 0M 0m, FLU =
      3M 4m, ITR = 1M 7m errors. The E test was quick and relatively simple to perform.
      Results using the E test compared favourably with those of the OD80 and it should
      be suitable for the routine susceptibility testing of yeasts to antifungal
      agents.

PMID- 9531069
TI  - The effect of the new triazole, voriconazole (UK-109,496), on the interactions of
      Candida albicans and Candida krusei with endothelial cells.
AB  - In this study, we investigated how voriconazole affects specific endothelial cell
      interactions utilizing both fluconazole-susceptibles and resistantR Candida
      albicans strains (C. albicansS and C. albicansR, respectively) as well as Candida
      krusei. Our data show that exposing C. albicansS to voriconazole significantly
      reduced its adherence to endothelial cells (p <0.001). The adherence of C.
      albicansR to endothelial cells was not affected by treatment with either
      antifungal agent. Exposure of C. albicans to both agents inhibited germ tube
      formation; however, voriconazole showed higher ability in inhibiting germination
      as compared with fluconazole. The effect of antifungals on germination was also
      tested during co-incubation of yeast cells with endothelial cells. Pretreated C.
      albicansS cells germinated on endothelial cells in the presence of voriconazole
      or fluconazole. However, the degree of germination was reduced by 81% and 16%,
      respectively. Similar results were observed with C. albicansR. Our data
      demonstrate that voriconazole treatment reduced the median germ tube length of C.
      albicansS and C. albicansR by approximately 60%, whereas fluconazole reduced the
      germ tube length of these strains by 27% and 63%, respectively (P < 0.0001 for
      each comparison). We compared the efficacy of voriconazole and fluconazole in
      protecting endothelial cells against damage caused by C. albicansS, C. albicansR,
      and C. krusei. Voriconazole and fluconazole reduced C. albicans-mediated
      endothelial cell injury by about 90% and 40%, respectively (P < 0.01 for each
      comparison). Additionally, voriconazole treatment significantly reduced C. krusei
      mediated injury to endothelial cells by 69% (P < 0.01), whereas fluconazole did
      not exhibit significant protection (P < 0.6). These results demonstrate that
      voriconazole, in addition to its direct inhibitory activity against fungi, may
      act against Candida spp. by interfering with critical host/parasite interactions,
      such as adherence and endothelial cell damage, as well as germination. Therefore,
      this triazole represents a new and promising agent for the treatment of
      disseminated candidal infections caused by both fluconazole-susceptible and 
      resistant species.

PMID- 9531070
TI  - Comparative in vitro activity of silver sulfadiazine, alone and in combination
      with cerium nitrate, against staphylococci and gram-negative bacteria.
AB  - Silver sulfadiazine (SSD), a topical antimicrobial agent, has been widely used
      for the prophylaxis and treatment of burn infections during the past 30 years. We
      determined the antimicrobial activity of SSD, alone and in combination with
      cerium nitrate (CN), gentamicin and amikacin against 130 recent clinical
      isolates, including multiresistant bacteria such as methicillin-resistant
      Staphylococcus aureus (MRSA) or Pseudomonas aeruginosa. The overall activity of
      SSD was good against all the tested strains and it was particularly high against
      MRSA (MIC90 100 microg/ml). CN showed no inhibitory effect, even up to 800
      microg/ml, on bacterial strains tested. The combination of SSD and CN was as
      active as SSD alone. In conclusion, SSD has a broad spectrum of activity at
      concentrations lower than those commonly used in clinical preparations. All
      strains were inhibited by less then one-fiftieth of the SSD "in use"
      concentration (10 mg/ml). Our data confirm the efficacy of this topical agent in
      the prevention and treatment of infections in burns or other surgical wounds and
      suggest its possible use in clearing staphylococcal carriage as an alternative to
      mupirocin.

PMID- 9531072
TI  - In vitro susceptibility of Staphylococcus aureus isolated from blood to currently
      used antistaphylococcal drugs.
AB  - Changes in antibiotic susceptibility was evaluated in 77 consecutive nosocomial
      clinical isolates of Staphylococcus aureus collected from 1986 to 1994 at the
      Umberto I Polyclinic of the University of Rome (63 isolates) and from 7 other
      Roman hospitals (14 isolates). Oxacillin resistance in these isolates increased
      from 39% during the 1980s to 69% during the 1990s. Significant increases in
      resistance to ciprofloxacin, clindamycin and rifampicin were observed among
      oxacillin-resistant strains. No resistance to glycopeptides was observed although
      both teicoplanin and vancomycin had slightly reduced antistaphylococcal activity.

PMID- 9531071
TI  - Two nosocomial strains of Stenotrophomonas maltophilia transferring antibiotic
      resistance to Proteus mirabilis P-38 recipient strain.
AB  - In this report we describe a specific transfer of carbenicillin and cephaloridine
      resistance determinants from two different strains of Stenotrophomonas
      maltophilia: No. 215 and 221 isolated from two critically ill patients treated in
      different Intensive Care Units of a large University Hospital in Ostrava, Czech
      Republic. These strains were resistant to flouroquinolones and the following beta
      lactam drugs: carbenicillin, cephaloridine, cefotaxime, ceftazidime, cefepime,
      imipenem, meropenem and aztreonam. Both strains transferred carbenicillin and
      cephaloridine resistance determinants, with rather different frequency, to
      Proteus mirabilis P-38. All carbenicillin-selected transconjugants were found by
      an indirect selection method to be co-resistant to cephaloridine only. In a
      second cycle of transfers Proteus mirabilis R+ strains directly transferred
      carbenicillin and cephalothin determinants to Escherichia coli K-12 No. 185 nal+
      lac+ recipient strain.

PMID- 9531073
TI  - Influence of protein binding on the pharmacodynamics of ceftazidime or
      ceftriaxone against gram-positive and gram-negative bacteria in an in vitro
      infection model.
AB  - The antibacterial activity of ceftriaxone and ceftazidime against Gram-positive
      and Gram-negative bacteria, clinically isolated from patients hospitalized in
      intensive care unit, was compared in vitro. The study was performed using a
      dynamic model in which the human kinetics of the drugs after i.m. administration
      were simulated. The antibacterial activity was tested by determining viable
      colony forming units (CFU) of bacteria/ml. Kill curves were constructed by
      plotting the log CFU/ml versus time. Simultaneously with CFU detection,
      ceftriaxone and ceftazidime concentrations were assayed by HPLC. The results
      obtained show that ceftriaxone and ceftazidime exert the same killing activity
      against the highly sensitive strains tested. Against the less sensitive strains,
      both drugs have initial good killing activity followed by bacterial regrowth
      using ceftriaxone while no regrowth was observed using ceftazidime. These data
      indicate that both ceftazidime and ceftriaxone exhibit primarily time-dependent
      bacterial killing. Moreover, only unbound drug appears to be effective, so only
      free drug should be considered in the pharmacokinetic-pharmacodynamic
      interaction.

PMID- 9531074
TI  - Pneumonia: the impact of risk factors on the outcome of treatment with meropenem
      and ceftazidime.
AB  - This analysis comprises data pooled from two clinical trials of meropenem (0.5 g
      8-hourly) versus ceftazidime (1 g 8-hourly) in hospitalized patients with
      community-acquired pneumonia. The clinical and bacteriological responses to
      treatment were assessed in relation to a range of risk factors previously linked
      to a poor clinical outcome. 393 patients (198 meropenem, 195 ceftazidime) were
      clinically evaluable while 230 (113 meropenem, 117 ceftazidime) were
      bacteriologically evaluable. Meropenem was highly effective, independent of
      associated risk factors, producing overall satisfactory clinical and
      bacteriological response rates at the end of therapy of 91.4% and 94.7%,
      respectively, similar to those produced by ceftazidime (90.3% and 92.3%,
      respectively). Clinical and bacteriological treatment outcome were similar in
      patients with up to three of the following key risk factors: age > or =65 years,
      male gender, serum urea >7 mmol/L, serum albumin <35 g/L and difficult-to-treat
      pathogens. Meropenem also achieved high clinical (85.7%) and bacteriological
      (89.3%) success rates in patients requiring ventilation, as did ceftazidime
      (81.6% and 87.1%, respectively). Both agents were highly effective against both
      Gram-negative and Gram-positive causative pathogens, including those organisms
      normally considered difficult to treat and typical of nosocomial pneumonia (e.g.
      Enterobacteriaceae, Staphylococcus aureus, Pseudomonas aeruginosa). Thus,
      meropenem and ceftazidime were highly effective in patients hospitalized with
      community-acquired pneumonia, irrespective of a number of concurrent risk factors
      (including those regarded as key risk factors). Furthermore, the analysis points
      to a role for meropenem 0.5 g 8-hourly in the treatment of nosocomial pneumonias
      that do not require intensive care unit admission and/or mechanical ventilation.
      Overall, this novel analysis of trial data suggests that incorporation of key
      risk factor endpoints into the initial design of pneumonia studies may prove to
      be a useful approach in defining appropriate antibiotic treatment for specific
      patient groups.

PMID- 9531075
TI  - Increased burn patient survival with once-a-day high dose teicoplanin and
      netilmicin. An Italian multicenter study.
AB  - This is the final report of a large, controlled, multicenter Italian study on
      immuno- and chemotherapy in adult patients with burns affecting 20 to 95% of
      total body surface area (mean 35%). The antibiotic treatment of burn patients
      consisted of topical silver sulfadiazine, short-term antimicrobial
      chemoprophylaxis with pefloxacin (800 mg i.v. qd) for the first 4 days and
      polychemotherapy with teicoplanin (800 mg i.v. qd) together with netilmicin (300
      mg i.m. qd) in one or more cycles of 5-12 days. At random, half of the patients
      received thymostimulin, 70 mg i.m. qd for the first month and every other day
      thereafter. The analysis at completion of 634 valid cases showed that when the
      results are stratified by means of the Roi risk index, 396 of the 530 patients
      who contracted wound infection (84%) after chemoprophylaxis were in the first
      three categories and a mean of 95% survived. Of the remaining 134 patients (Roi
      index 4-5) only 50% survived. There was no difference in survival of the
      immunotherapy group in comparison with the parallel group without thymostimulin.
      The short-term antimicrobial prophylaxis prevented wound infection in only 104 of
      634 patients (16%) and they were at low risk (84% Roi index 1). Of the bacterial
      pathogens involved in septic complications Staphylococcus aureus and Pseudomonas
      aeruginosa were prevalent (86%): eradication was achieved in 43% of patients and
      clinical cure or improvement were seen with combination chemotherapy in 64% of
      all patients, mainly with only one treatment cycle. This value increased to 79%
      for the 395 protocol-complying patients and went down to 20% in the 135 non
      compliers. The total survival of complier and non-complier patients was 447 of
      the 530 valid patients (84%). The overall mortality of the 634 evaluable patients
      was 13.1%, ranging from less than 2% to 68%. Burn mortality was directly
      proportional to the percentage of burned body surface area, to increasing age and
      other variables of the Roi index, a 50% mortality being associated with a 72.5%
      total body surface area burned. Normoergic burn patients had a mortality rate of
      9.1% versus 35.7% in anergic patients.

PMID- 9531076
TI  - Preoperative antimicrobial prophylaxis with a long-acting cephalosporin for
      thoracic surgery in 192 non small cell lung cancer patients.
AB  - The efficacy of preoperative antibiotic prophylaxis in thoracic surgery with a
      single dose of ceftriaxone was investigated. Here we report the results of a
      prospective study including 192 patients undergoing thoracic surgery for non
      small cell lung cancer. Overall, the postoperative infection rate, as measured by
      wound, respiratory tract, and urinary tract infections, was 8.3% (16/192).
      Ceftriaxone was well tolerated, and no allergic or other adverse reactions were
      reported. A single preoperative dose of ceftriaxone was cost-effective and
      allowed considerable saving of time, material, labor costs and money. This study,
      even though open and non-comparative, suggests that the routine use of a single
      preoperative dose of ceftriaxone provides a cost-effective prophylaxis for
      patients undergoing major thoracic operations.

PMID- 9531077
TI  - Treatment of atypical pneumonia with azithromycin: comparison of a 5-day and a 3
      day course.
AB  - The efficacy of a 5-day regimen consisting of 500 mg in a single dose on the
      first day followed by 250 mg once daily for 4 consecutive days was compared with
      that of a 3-day course of azithromycin given in single daily doses of 500 mg for
      treatment of atypical pneumonia. Adult patients hospitalized with atypical
      pneumonia in the years 1990 to 1993 were studied retrospectively. For each
      patient, the medical history, laboratory data, the results of serological tests,
      chest radiographs and treatment outcome were reviewed. Out of 148 patients with
      atypical pneumonia, 40 were treated with azithromycin for 5 days (Group 1) and 41
      for 3 days (Group 2). The success rate in Group 1 was 80% (32 patients). Eight
      patients did not respond to treatment: 5 had significant complement fixing
      antibody titers to adenovirus and in 3 the etiology was unknown. The success rate
      in Group 2 was 88% (36 patients). Azithromycin was ineffective in all 3 patients
      with adenoviral pneumonia, in 1 patient with Q fever, and in 1 patient with no
      identified pathogen. Azithromycin is equally effective as treatment of atypical
      pneumonia in adult patients if given for 3 or 5 days at the same total dose.

PMID- 9531079
TI  - Advertising refractive surgery.

PMID- 9531078
TI  - Osteosarcoma of the extremities with synchronous lung metastases: long-term
      results in 44 patients treated with neoadjuvant chemotherapy.
AB  - Between September 1986 and September 1991, 44 patients with lung metastases
      originating from an osteosarcoma of an extremity were treated with: primary
      chemotherapy, simultaneous resection of primary and metastatic lesions (when
      feasible), and then further chemotherapy. After primary chemotherapy, lung
      metastases disappeared in 5 patients, whereas in 11 patients they remained
      surgically unresectable. All 16 patients received local treatment of the primary
      tumor only. In the remaining 28 patients simultaneous surgical treatment of the
      primary and the metastatic tumor was performed. The removal of metastatic lesions
      was complete in 25 and incomplete in 3 patients. With a median follow-up of 8
      years (5.5-10.8) all 14 patients who never achieved a tumor-free status died. Of
      the 30 patients who achieved remission 5 (17%) remained continuously free of
      disease and 25 developed new metastases, associated with local recurrence in 4
      cases. The 5-year overall survival for all 44 patients of the study was 14%, and
      the 5-year disease-free survival for the 30 patients who reached remission was
      17%. These results are significantly worse than those achieved with the same
      chemotherapy protocol in 144 contemporary patients with localized disease at
      presentation (73% disease-free and 79% overall survival). We conclude that,
      despite aggressive chemotherapy which is successful in patients with localized
      disease, the prognosis remains very poor for patients with osteosarcoma of the
      extremities with lung metastases at presentation, and justifies the use of novel
      therapies.

PMID- 9531080
TI  - Source of excimer laser plume photographs acknowledged.

PMID- 9531081
TI  - Laser in situ keratomileusis for myopia from -5.50 to -11.50 diopters with
      astigmatism.
AB  - PURPOSE: To determine the efficacy, predictability, safety, and short-term
      stability of laser in situ keratomileusis (LASIK) in treating patients with high
      myopia and astigmatism. METHODS: We retrospectively studied the results of our
      initial 119 eyes with myopia ranging from -5.50 to -11.50 D and astigmatism less
      than 4.00 D that underwent LASIK with the Nidek EC-5000 excimer laser. Follow-up
      was at 1 day, 1 month, and 3 to 6 months; follow-up was 71% (84 eyes) at the 3 to
      6 month visit (average 4.5 months). RESULTS: Of the 84 eyes with 3 to 6 months of
      follow-up, mean baseline spherical equivalent refraction was -8.62 +/- 1.27 D and
      mean cylinder was -1.84 +/- 1.02 D. Mean postoperative spherical equivalent
      refraction at the last examination was -0.61 +/- 0.84 D and mean cylinder was 
      0.39 +/- 0.38 D, with 83% (70 eyes) achieving a spherical equivalent refraction
      within +/-1.00 D of emmetropia, and 56% (47 eyes) within +/-0.50 D. Mean
      regression of spherical equivalent from 1 day to 1 month was less than -0.50 D
      and refractions were stable between 1 month and 3 to 6 months. An uncorrected
      visual acuity of 20/40 or better was noted in 84% (71 eyes) of these eyes on day
      1 after surgery, in 75% (63 eyes) at 1 month, and in 77% (65 eyes) at 3 to 6
      months. Twenty-two percent (18 eyes) of these eyes achieved 20/20 or better
      uncorrected visual acuity at 3 to 6 months; only 17% (14 eyes) had 20/20 or
      better spectacle-corrected visual acuity before surgery. One patient lost two or
      more lines of spectacle-corrected visual acuity at the last examination due to
      epidemic keratoconjunctivitis. CONCLUSION: LASIK with the Nidek EC-5000 excimer
      laser appears to be an effective and safe means for treating patients with high
      myopia and astigmatism. Studies with longer follow-up will help evaluate the long
      term stability of the procedure and the possibility of late complications.

PMID- 9531082
TI  - Laser in situ keratomileusis to correct hyperopia from +4.25 to +8.00 diopters.
AB  - OBJECTIVE: To evaluate the efficacy and predictability of laser in situ
      keratomileusis (LASIK) for hyperopia in a prospective study of 54 eyes of 29
      patients. METHODS: Before LASIK, 44 eyes (81.48%) had a spectacle-corrected
      visual acuity of 20/20 or better, and 54 eyes (100%) had 20/40 or better. Surgery
      was performed under topical anesthesia using the Keracor 116 excimer laser and
      Chiron automated corneal shaper. Mean follow-up was 19 months. RESULTS: Mean
      baseline uncorrected hyperopia was +6.50 +/- 1.33 D (range, +4.25 to +8.00 D).
      Mean uncorrected manifest spherical equivalent refraction was +0.44 +/- 1.95 D at
      18 months after LASIK. Twenty-one eyes (38.8%) were within +/-0.50 D of
      emmetropia, 41 eyes (75.92%) were within +/-1.00 D, and 47 eyes (87.03%) were
      within +/-2.00 at 18 months after LASIK. Uncorrected visual acuity was 20/20 or
      better in eight eyes (14.81%) and 20/40 or better in 36 eyes (66.66%) 18 months
      after LASIK. Regression and undercorrection of more than 2.00 D occurred in seven
      eyes (12.9%) between the 3 and 6 month examinations; three of these seven eyes
      (42.8%) required retreatment to correct residual hyperopia. Three eyes (6.8%)
      lost two or more lines of spectacle-corrected visual acuity. CONCLUSION: Excimer
      laser keratomileusis in situ with the Keracor 116 appears to be an effective and
      safe procedure to decrease low and moderate hyperopia, but the predictability of
      the procedure needs improvement.

PMID- 9531083
TI  - Excimer laser photorefractive keratectomy for presbyopia: 24-month follow-up in
      three eyes.
AB  - BACKGROUND: For some patients, standard optical correction for presbyopia is not
      satisfactory. Using a specially designed mask, we developed a procedure for
      correcting presbyopia with excimer laser photorefractive keratectomy (PRK).
      METHODS: A mask consisting of a mobile diaphragm formed by two blunt blades was
      used to ablate a 10 to 17 microm deep semilunar-shaped zone immediately below the
      pupillary center, steepening the corneal curvature in that area. Three eyes of
      three presbyopic patients were treated, aiming at a near addition of +3.00 D.
      Follow-up time was 24 months. RESULTS: After an initial regression of 1.00 D
      during the first 6 months, the presbyopic correction remained stable for the
      duration of the follow-up period, enabling uncorrected near vision of J3 in all
      three eyes. Uncorrected distance visual acuity was not altered. Contrast
      sensitivity (Regan) was slightly decreased only at the 11% level.
      Videokeratography confirmed corneal steepening in the ablated area. CONCLUSION:
      The visual and refractive outcome of excimer laser PRK for presbyopia with the
      Aesculap-Meditec MEL 60 is promising, especially in view of the 2-year follow-up.

PMID- 9531084
TI  - Removal of corneal epithelium with phototherapeutic technique during multizone,
      multipass photorefractive keratectomy.
AB  - BACKGROUND: The therapeutic mode of the VISX 20/20 excimer laser was used to
      remove the corneal epithelium prior to performing photorefractive keratectomy
      (PRK) with a multizone, multipass technique. METHODS: A retrospective analysis
      was performed of 120 eyes of 90 patients that were treated for preoperative
      spherical refractive errors from -1.00 to -7.00 diopters (D) (mean -3.90 D, SD
      1.54) by one surgeon (DGJ) over 7 months. RESULTS: Six-month follow-up was
      obtained in 76 eyes (63%). Sixty-nine eyes (91%) achieved a spherical equivalent
      refraction within +/-1.00 D of emmetropia. Regression of effect averaged -0.35 D
      (SD 0.53 D) from 1 to 6 months after surgery. Mean postoperative uncorrected
      visual acuity at 6 months was 20/25 (range 20/15 to 20/200). Seventy-three eyes
      (96%) achieved uncorrected visual acuity of 20/40 or better, 67 (88%) achieved
      uncorrected visual acuity of 20/25 or better, and 76 (71%) achieved 20/20 or
      better. Three eyes (4%) lost one line of spectacle-corrected visual acuity; no
      eye lost more than one line. There were no significant surgical complications.
      CONCLUSION: Removal of corneal epithelium with the Summit Excimed UV 200 LA
      excimer laser using multizone, multipass photoablation yields visual and
      refractive results that compare favorably with published PRK series with
      excellent short-term stability.

PMID- 9531085
TI  - Long-term effects of radial keratotomy on the corneal endothelium.
AB  - BACKGROUND: The long-term effects of radial keratotomy on the corneal endothelium
      are not well understood. We evaluated the effects of radial keratotomy on the
      corneal endothelium on the central and midperipheral corneal endothelium.
      METHODS: Anterior radial keratotomy in 25 eyes was performed and patients were
      followed for a duration of 4 to 10 years after surgery. Eleven non- contact lens
      wearing control eyes did not have surgery and were followed for the same period.
      Morphometric analysis of specular microscopic images was performed with regard to
      cell density, percent hexagonality, and coefficient of variation. RESULTS: Mean
      corneal endothelial cell loss rates were 0.4% per year in the radial keratotomy
      group and 0.9% in the untreated control group over the study duration (mean 7
      yr). Morphometric analysis of the cells failed to show a significant change in
      hexagonality and coefficient of variation. Evaluation of the midperipheral
      corneal cell counts demonstrated a 1% per year cell loss rate. The cell loss
      rates in radial keratotomy patients followed over this period were consistent
      with that noted for normal aging (0.5 to 2.5% per year). CONCLUSION: Radial
      keratotomy does not cause accelerated endothelial cell loss over 4 to 10 years.

PMID- 9531087
TI  - Peripheral melt of flap after laser in situ keratomileusis.
AB  - BACKGROUND: Laser in situ keratomileusis (LASIK) is an effective procedure to
      correct myopia. It may have complications related to the flap, such as epithelial
      ingrowth and stromal melt. METHODS: We report on a patient who developed
      extensive epithelial ingrowth and partial keratolysis of the flap following
      LASIK. This complication was treated by lifting the flap and removing the
      epithelium from within the interface. RESULTS: Progressive keratolysis (stromal
      melt) can result in irregular astigmatism and loss of vision as well as
      photophobia and ciliary injection. The pathogenesis is not completely understood
      although the epithelial ingrowth in the interface is always present, and
      epithelial-stromal interaction with production of proteases may be involved.
      CONCLUSION: Epithelial ingrowth may develop in the lamellar interface after LASIK
      and be associated with melting of the edge of the flap. This undesirable
      complication can be successfully managed with early surgical removal of the
      epithelium and proper attachment of the flap.

PMID- 9531086
TI  - Assessment of corneal wound healing by interactive topography.
AB  - INTRODUCTION: Constitutive properties of the cornea and wounds within the cornea
      have been measured previously by destructive methods in which a strip of cornea
      was removed, placed on an instrument, and stretched until broken. To assess
      corneal wound healing and the interaction of medication, incision patterns and
      other clinical issues, we present a simple, noninvasive test of corneal wound
      healing utilizing a videokeratoscope and Honan balloon. METHODS: A pre-test
      corneal topography was performed. The Honan balloon was placed on the eye at a
      pressure of 30mm mercury for 5 minutes. After removal of the balloon, additional
      corneal topographies were performed for comparison to the baseline topography.
      Study eyes were divided into six groups: 15 eyes in the normal group not involved
      in the Honan balloon test, 15 eyes formed a control group without previous ocular
      surgery, 15 eyes were within 3 months of radial keratotomy (RK), 15 eyes were
      more than 9 months after RK, 12 eyes had previous automated in situ
      keratomileusis (ALK), and 12 eyes had previous penetrating keratoplasty (PK).
      RESULTS: Average videokeratometric flattening was reported for all groups at
      intervals of 1, 2, and 3 minutes after removal of the Honan balloon. The normal
      group flattened by 0.04 +/- 0.10 D (range, +0.10 to -0.12 D) at 1 minute; 0.02 +/
      0.08 D (range, +0.10 to -0.10 D) at 2 minutes; and 0.02 +/- 0.06 D (range, +0.10
      to -0.09 D) at 3 minutes. The control group flattened by -0.10 +/- 0.10 D (range,
      +0.30 to -0.30 D) at 1 minute; 0.01 +/- 0.12 D (range, +0.15 to -0.25 D) at 2
      minutes; and 0.07 +/- 0.11 D (range, +0.14 to -0.18 D) at 3 minutes. The 3-month
      RK group flattened 0.95 +/- 0.23 D (range, 1.35 to 0.67 D) at 1 minute; 0.53 +/-
      0.16 D (range, 0.71 to 0.39 D) at 2 minutes; and 0.40 +/- 0.15 D (range, 0.56 to
      0.30 D) at 3 minutes. The 9-month RK group flattened 0.10 +/- 0.13 D (range, 0.23
      to 0.02 D) at 1 minute; 0.10 +/- 0.12 D (range, 0.18 to -0.01 D) at 2 minutes;
      and 0.01 +/- 0.14 D (range 0.05 to 0.10 D) at 3 minutes. The ALK group flattened
      0.65 +/- 0.42 D (range 0.98 to 0.38 D) at 1 minute; 0.27 +/- 0.19 D (range 0.39
      to 0.10 D) at 2 minutes; and 0.21 +/- 0.17 D (range, 0.29 to 0.09 D) at 3
      minutes. The PK group flattened 1.30 +/- 0.60 D (range, 1.75 to 0.90 D) at 1
      minute; 1.18 +/- 0.43 D (range, 1.51 to 0.98 D) at 2 minutes; and 0.41 +/- 0.57 D
      (range, 0.88 to 0.30 D) at 3 minutes. CONCLUSIONS: We have established normal
      corneal wound healing curves from preliminary data utilizing Buzard interactive
      topography on normal control eyes and after radial keratotomy, automated lamellar
      keratoplasty, and penetrating keratoplasty. Deviation from these normal curves
      indicates either excessive or inadequate wound healing.

PMID- 9531088
TI  - Therapeutic alloplastic laser in situ keratomileusis for myopia.
AB  - BACKGROUND: A new technique, therapeutic alloplastic laser in situ keratomileusis
      to correct high myopia, is introduced. METHODS: Therapeutic alloplastic laser in
      situ keratomileusis consists of neutral homoplastic epikeratoplasty combined with
      superficial keratectomy performed with an excimer laser and/or a microkeratome.
      Indications for the technique are: myopia over 20 diopters (D), eyes with corneal
      scarring after photorefractive keratectomy (PRK), complications following
      keratomileusis, radial keratotomy complications with undercorrection, and
      keratoconus suspect myopic eyes. RESULTS: In all five eyes we achieved precise
      corneal lathing with the microkeratome or the excimer laser, and obtained a clear
      allograft. In all eyes, we maintained or improved the patient's spectacle
      corrected visual acuity related to baseline values. We did not induce
      astigmatism, and corneal thickness was almost unchanged. CONCLUSIONS: Advantages
      of therapeutic alloplastic laser in situ keratomileusis are that it provides a
      Bowman's layer for the cornea following keratectomy, it is possible to lathe
      ablation diameters larger than 5 mm, it prevents the appearance of corneal haze,
      and reduces the need for corticosteroid treatment.

PMID- 9531089
TI  - Extended wear disposable soft contact lenses as an alternative to photorefractive
      keratectomy: report of 4 years experience.

PMID- 9531090
TI  - ACOEM's eight best ideas for workers' compensation reform. American College of
      Occupational and Environmental Medicine.

PMID- 9531091
TI  - Reproductive health outcomes among female flight attendants: an exploratory
      study.
AB  - Recent studies have suggested that female flight attendants may experience
      increased rates of spontaneous abortion. We conducted a survey of female flight
      attendants who were pregnant at any time between January 1, 1990, and December
      31, 1991 (n = 418) using a mailed self-administered interest survey (response
      rate, 60 %) and follow-up questionnaire regarding reproductive outcomes and
      potential risk factors for adverse outcomes (response rate, 64%). The cumulative
      hazard of spontaneous abortion was 17% when maternal age, smoking, alcohol use,
      and prior spontaneous abortions were control led for, using a Cox life-table
      regression model. Of the female flight attendants who worked outside the home, 47
      of 321 (15%) experienced a spontaneous abortion, compared with 6 of 73 (8%) who
      did not work outside the home during the pregnancy period (odds ratio [OR] =
      1.91, 95 % confidence interval [CI] = 0.78-4.66). Flight attendants who
      experienced a spontaneous abortion during their first pregnancy during the study
      period reported working significantly more flight hours per month during their
      pregnancy (74 hours per month) than did flight attendants who delivered a live
      birth (64 hours per month) (Student's t = -3.30, P = 0.002). We conclude that
      although the results of this study must be considered preliminary because of the
      relatively low overall response rate (38%), we did not find an overall increased
      risk for spontaneous abortion among flight attendants, compared with other
      working women (10%-20%). Women who continue working as flight attendants during
      pregnancy and those who work relatively higher numbers of flight hours during
      pregnancy may, however, be at increased risk for spontaneous abortion, compared
      with flight attendants who do not perform such work.

PMID- 9531092
TI  - Evidence on N-acetyltransferase allele-associated metabolism of hydrazine in
      Japanese workers.
AB  - Hydrazine (N2H4), which has been categorized as a weak carcinogen, is a chemical
      with the one of the largest production rates in Japan. We have investigated the
      effects of acetylation phenotypes on the metabolism of hydrazine. Genotypes of N
      acetyl transferases, NAT2*, were determined using polymerase chain reaction for
      297 male workers. Biological and exposure monitoring were also conducted. The
      rapid and intermediate acetylators accounted for 45% each, and the slow
      acetylators accounted for 10%. Biological half-lives were significantly different
      among the three acetylation phenotypes (analysis of variance, P < 0.05): 3.94+/
      1.70 hours for slow acetylators, 2.25+/-0.37 hours for intermediate acetylators,
      and 1.86+/-0.67 hours for rapid acetylators. Among Japanese, rapid and
      intermediate acetylators are the major phenotypes, which is in sharp contrast
      with those among Caucasians. We conclude that biological monitoring should take
      genetic factors, which may vary dramatically among different populations, into
      account.

PMID- 9531093
TI  - Respiratory symptoms and pulmonary function among stainless steel welders.
AB  - In the last few years, many studies have been carried out concerning the effects
      of fumes from stainless steel (SS) welding on the health of welders. The
      respiratory effects of exposure to SS welding fumes have already been studied,
      but the results of lung function investigations have not been consistent.
      However, the main factor of risk for the welders' health seems to be related to
      the great concentration of chromium and nickel contained in fumes coming from SS
      welding. The aim of this study was to detect the chronic effects of SS welding
      exposure on pulmonary symptoms and ventilatory function tests. Respiratory
      symptoms and lung function tests were studied in 134 SS welders and 252 controls
      (C). Welders and controls were of similar average age, height, and duration in
      employment. The smoking habits of the groups were also similar. The medical
      questionnaire on respiratory symptoms was a version of the Medical Research
      Council questionnaire, modified by the British Occupational Hygiene Society. The
      flow-volume curves were performed with a calibrated pneumotachograph spirometer
      before each subject started working. After adjustment for tobacco habits, the SS
      welders presented a higher prevalence of bronchial irritative symptoms such as
      cough (P = 0.01) or sputum production (P = 0.02) than the controls. On the other
      hand, chronic bronchitis appeared to be significantly linked to tobacco
      consumption. The pulmonary function analysis underscored no significant
      difference between stainless steel welders and controls (forced expiratory volume
      in one second, observed/predicted: SS = 0.99 vs C = 0.98; maximal midexpiratory
      flow, observed/predicted: SS = 0.90 vs C = 0.92; maximal expiratory flow at 50 %
      of the forced vital capacity, observed/predicted: SS = 0.95 vs C = 0.95). On the
      other hand, by the mean of the two-ways analysis, a significant tobacco effect
      was found, without exposure or interaction of tobacco-exposure effects. There was
      no influence of the specific welding processes on the spirographic parameters,
      but a decrease in spirographic values after 25 years of welding activity was
      evident. The results of multiple regression indicated that age was not a
      confounding factor.

PMID- 9531094
TI  - Modeling the acute neurotoxicity of styrene.
AB  - Styrene is a widely used industrial solvent associated with acute neurotoxicity.
      To investigate the relationships between exposure, blood concentrations, and the
      appearance of neurotoxic effects, four healthy males were exposed to styrene
      concentrations of 5-200 ppm in four different exposure-time profiles. A digit
      recognition test and P300 event-related evoked potential were used to measure
      neurologic function. A physiologically based kinetic (PBK) model generated close
      predictions of measured styrene blood concentrations, in the range of 0.01-12
      mg/L, from this and 21 previous studies. Simulated peak brain concentration,
      durationXaverage exposure, and peak exposure level were predictive of toxicity.
      Central nervous system effects were expected at a blood concentration near 2.4
      mg/L. A standard of 20 ppm was expected to protect styrene-exposed workers from
      acute central nervous system toxicity under light work conditions.

PMID- 9531095
TI  - Building-associated pulmonary disease from exposure to Stachybotrys chartarum and
      Aspergillus versicolor.
AB  - The authors present an outbreak of disease associated with exposure to
      Stachybotrys chartarum and Aspergillus species. A courthouse and two associated
      office buildings had generated discomfort among employees for two years since
      initial occupancy. Multiple interventions had been unsuccessful An initial
      evaluation of 14 individuals identified three with potential asthma and three
      with symptoms consistent with interstitial lung disease. A clinical screening
      protocol to identify individuals who should be removed from work identified three
      likely and seven possible cases of building-related asthma. Detailed
      environmental and engineering assessments of the building identified major
      problems in mechanical system design, building construction, and operational
      strategies leading to excess moisture and elevated relative humidities. Moisture
      damaged interior surfaces in both buildings were contaminated with S. chartarum,
      A. versicolor, and Penicillium species. Aspergillus species, especially A.
      versicolor, at concentrations of 10(1) to 10(4)/m3 dominated the indoor air under
      normal operating conditions. Bulk samples also revealed large quantities of
      Stachybotrys. A questionnaire survey of the three case and two control buildings
      documented between three- and 15-fold increases in symptoms. A nested case
      control study suggested emphysematous-like disease in individuals meeting
      questionnaire definitions for cases. Replication of analysis strategies used in
      similar previous investigations suggested an association between worsening
      symptoms and decreased diffusing capacity of the lung. Performance on
      neuropsychological measures was similar for both cases and controls, although
      workers with symptoms reported increased levels of current but not past
      psychiatric symptomatology. Chemical analyses demonstrated the presence of
      satratoxins G and H. Cytotoxic laboratory analyses demonstrated the presence of
      agents with biological effectiveness in bulk materials. No association was seen
      between IgE or IgG antibodies and the presence of disease. This outbreak
      represents a likely human response to inhaled fungal toxins in indoor
      environments. Moisture indoors represents a public health issue currently
      inadequately addressed by building, health, or housing codes.

PMID- 9531096
TI  - Sex as a variable can be a surrogate for some working conditions: factors
      associated with sickness absence.
AB  - More than twice as many workdays are lost to illness than for personal or family
      reasons. We examine possible workplace determinants of sickness absence among
      French workers in the food processing industry. These workers are exposed to a
      variety of environmental and organizational constraints: cold, uncomfortable
      postures, assembly-line work, and irregular schedules. In 1987-1988, a medical
      examination and questionnaire were administered to 558 men and 790 women as part
      of a study of 17 poultry slaughterhouses and 6 canning factories. Women's and
      men's working conditions were very different, and their sickness absences for
      musculoskeletal and respiratory illnesses were related to some of their specific
      working conditions: cold exposure, ill-adapted work stations, and problems with
      their supervisors and co-workers. If male and female workers were combined into a
      single analysis that adjusted for sex, many of the associations operant for a
      single sex could no longer be seen.

PMID- 9531097
TI  - Length of disability and cost of work-related musculoskeletal disorders of the
      upper extremity.
AB  - There is little information on the length of disability (LOD) reported for work
      related musculoskeletal disorders of the upper extremity (WMSDUE). For this
      study, LOD, cost, and the relationship between LOD and cost were derived from a
      large workers' compensation company's claims data for 1994 WMSDUE (n = 21,338).
      The average LOD was 87 days, with a median of zero days. For those claims with at
      least one day of compensable disability (25.2%), the average and median LOD were
      294 and 99 days, respectively. The distribution of cost was skewed, with the
      average cost of a claim being 13 times higher than its median. Approximately 60%
      of the claims cost $1000 or less. Additionally, the 6.8% of the claims with an
      LOD greater than one year accounted for 59.9% of the cost and 75% of the total
      disability days. The majority of WMSDUE claimants did not lose sufficient time to
      qualify for indemnity. For those who did receive lost time wages, a disability
      duration of more than three months was typical.

PMID- 9531098
TI  - Exposure of casino employees to environmental tobacco smoke.
AB  - Environmental and medical evaluations were performed to evaluate occupational
      exposure to environmental tobacco smoke (ETS) among casino employees. Air
      concentrations of both nicotine and respirable dust were similar to those
      published in the literature for other non-industrial indoor environments. The
      geometric mean serum cotinine level of the 27 participants who provided serum
      samples was 1.34 nanograms per milliliter (ng/mL) (pre-shift) and 1.85 ng/mL
      (post-shift). Both measurements greatly exceeded the geometric mean value of 0.65
      ng/mL for participants in the Third National Health and Nutrition Examination
      Survey (NHANES III) who reported exposure to ETS at work. This evaluation
      demonstrates that a sample of employees working in a casino gaming area were
      exposed to ETS at levels greater than those observed in a representative sample
      of the US population, and that the serum and urine cotinine of these employees
      increased during the workshift.

PMID- 9531099
TI  - The Darwinian evolution of health care.

PMID- 9531100
TI  - Transurethral microwave thermotherapy: strategies to ensure successful outcomes
      with Prostasoft 2.0.
AB  - Transurethral microwave thermotherapy (TUMT) is a unique and promising method of
      treating benign prostatic hyperplasia. Clinical outcomes are related to thermal
      dose delivered. In 359 consecutive patients, strategies to increase thermal dose
      using the FDA-approved Prostasoft 2.0 delivered a mean of 148 kJ, which was
      almost 50 kJ more than the U.S. FDA trials. These strategies include careful
      preoperative patient teaching, exclusion of very small prostates, ketorolac,
      prewarming of the prostaprobe, antitorque of the rectal probe, use of urethral
      cooling adjustment during power ramping, and no manual power interruptions.
      Clinical outcomes improved without any significant adverse events. Peak urinary
      flow increased in 4 months by 5.5 mL/sec.

PMID- 9531101
TI  - High-dose rate iridium192 afterloading therapy in combination with external beam
      irradiation for localized prostate cancer.
AB  - Development of afterloading techniques in combination with external radiotherapy
      allows for curative therapy modality for stage C prostate cancer. Between 10/92
      and 12/95 128 patients were treated. Stage B and C tumors were found in 36 and 89
      cases, respectively. All patients were pathologically proven to be node-negative
      by laparoscopic node dissection of the fossa obturatoria region. 9 Gy a week was
      applied during the first and second weeks of treatment (10/92-12/93: 10 Gy each
      week) interstitially with high-dose rate iridium192 brachytherapy to the
      prostate. After this, a four-field box of external beam radiation therapy was
      given to the prostate to a dose of 45 Gy/25 fractions (10/92-12/93: 40 Gy/20
      fractions). Before starting treatment median PSA was 13.8 ng/ml. The median PSA
      3, 12, and 24 months after completion of therapy was 1.2, 0.78, and 0.75 ng/ml,
      respectively. Negative biopsies 12 and 24 months after therapy were observed in
      56% (49/87) and 72% (31/43), respectively.

PMID- 9531103
TI  - Renal imaging with spiral CT scan: clinical applications.
AB  - Spiral computed tomography (CT) is an imaging modality that utilizes the rapid
      acquisition of cross-sectional data that can be reconstructed in a number of
      useful ways. We briefly describe the technology of spiral CT and recent
      advancements that have made spiral CT feasible. The advantages over conventional
      CT and angiography are reviewed. Urologic clinical applications are discussed
      including: detection of a crossing vessel prior to endopyelotomy for
      ureteropelvic junction (UPJ) obstruction, evaluating renal vascular anomalies
      preoperatively, and assistance in preoperative planning prior to partial
      nephrectomy in benign and malignant disease. Spiral CT has numerous advantages
      over conventional CT and angiography, and will likely have a notable role in
      future renal imaging.

PMID- 9531102
TI  - Pubovaginal fascial slings.
AB  - The first pubovaginal fascial sling was reported in 1907, however, until recently
      this procedure was rarely utilized except after other incontinence procedures had
      failed. Currently, a pubovaginal sling is indicated as the primary incontinence
      procedure if intrinsic sphincter deficiency or coexisting intrinsic sphincter
      deficiency and urethral hypermobility are diagnosed preoperatively. Additionally,
      incontinence secondary to urethral hypermobility should be treated with a
      pubovaginal sling if the patient has a high risk of postoperative failure due to
      obesity, chronic cough, or repetitive strenuous activity. Pubovaginal slings are
      relatively easy to perform and yield reliably good results with minimal
      morbidity. We describe our current technique and results using pubovaginal slings
      for stress incontinence in women.

PMID- 9531104
TI  - A novel continent cutaneous reservoir: application of appendiceal Mitrofanoff
      principle to Stanford pouch.
AB  - We describe our modification of Stanford pouch orthotopic bladder replacement
      both by formation of the pouch with absorbable staples (poly-GIA) and diverting
      it with the appendiceal Mitrofanoff conduit. This operation was performed on two
      patients with focal invasive bladder cancer--a male patient with bladder extrofia
      and a patient with a severely contracted bladder due to interstitial cystitis. No
      operative or postoperative complications were encountered. Follow-up after
      operation ranged between 6 and 16 months. The functional and cosmetic results of
      the operation were satisfactory. This operative modification may be considered
      for the patient requiring cystectomy who is not a candidate for orthotopic
      bladder replacement.

PMID- 9531105
TI  - Comparison of lighted ureteral catheter luminance for laparoscopy.
AB  - Urologists may be asked to place a lighted ureteral catheter for laparoscopic
      surgeons. Presumably, the lighted ureteral catheter with the greatest luminance
      will provide the best visual roadmap to the ureter during laparoscopy. The
      purpose of this article was to compare the luminance of three lighted ureteral
      catheters and characterize technical characteristics so that urologists could
      select the lighted ureteral catheter most appropriate for laparoscopy. Four
      lighted ureteral catheters were evaluated: Cook 5F single lumen, Cook 5F double
      lumen, Cook 7F, and Rusch 5F. Each catheter was attached to a standard fiber
      optic light source at maximum output. Each catheter was placed in a porcine
      ureter. Luminance was measured with a photometer in a dark room. Luminance was
      characterized at catheter locations corresponding to the proximal, middle, and
      distal ureter. The luminance measured in foot-Lamberts (fL) in the middle ureter
      for each catheter was as follows: Cook 5F single lumen 98+/-47, Cook 5F double
      lumen 42+/-14, Cook 7F 98+/-11, Rusch 5F 58+/-45 (p=.01). The luminance (fL) in
      the distal ureter for each catheter was: Cook 5F single lumen 129+/-40, Cook 5F
      double lumen 110+/-108, Cook 7F 22+/-2, Rusch 5F 49+/-30 (p=.02). The luminance
      was not significantly different among the catheters when measured in the proximal
      ureter. The Cook 5F single-lumen ureteral catheter overall has the greatest
      luminance. This catheter should be easiest to identify at laparoscopy.

PMID- 9531106
TI  - Endoscopic colposuspension with simplified extraperitoneal approach.
AB  - The retropubic colposuspension (Burch procedure) has been proven an effective
      treatment for female genuine stress urinary incontinence. During this decade,
      laparoscopic approach has gained access in continence surgery also. Endoscopic
      colposuspension can be performed either extraperitoneally or transperitoneally.
      If there is no need for intra-abdominal procedures the extraperitoneal approach
      for colposuspension is feasible. Generally a balloon dissection is used to
      develop the extraperitoneal space, but here we present a modified technique where
      no balloon is needed. This modification is easy to perform, quicker and decreases
      the costs of the procedure compared to transperitoneal approach. We also
      summarize the results of our first 46 patients, 24 of which were operated
      extraperitoneally and 22 by transperitoneal approach with concomitant pelvic
      surgery.

PMID- 9531107
TI  - Fragment of a catheter as a foreign body in the kidney.
AB  - Foreign bodies in the kidney are unusual. A review of the literature disclosed
      few reports of renal foreign body from nontraumatic causes. In this article, we
      report a case of gross hematuria due to iatrogenic foreign body in the kidney
      from ureteral endoscopy. The catheter fragment eluded diagnosis for 18 months
      until it was discovered and retrieved by means of a flexible ureteroscope. To our
      knowledge, this is the first report of this complication and presentation
      following endoscopic manipulation of the upper ureteral tract.

PMID- 9531108
TI  - Endoscopic management of complete obstruction of a ureteroneocystostomy in an
      infant.
AB  - We present the case of an 18-month-old female who, after bilateral
      ureteroneocystostomies, developed complete obstruction at the left
      ureteroneocystostomy site. Using endourologic techniques, patency of the
      ureteroneocystostomy was re-established and has remained unobstructed during her
      4-year follow-up.

PMID- 9531109
TI  - The radiographic diagnosis of pelvic lipomatosis.
AB  - We describe a patient who initially presented with asymptomatic hydronephrosis.
      He underwent extensive radiologic evaluation which led to the diagnosis of pelvic
      lipomatosis. The possible etiology, workup, and treatment options of this unusual
      entity are discussed.

PMID- 9531110
TI  - Helicobacter pylori and gastric cancer: what to tell our patients and who to
      treat?

PMID- 9531112
TI  - Helicobacter pylori and gastric cancer: what is the real risk?
AB  - Some epidemiological data point to an association between infection from
      Helicobacter pylori (Hp) and gastric cancer, although several unresolved issues
      still cast doubts on the real weight of this association. These issues are as
      follows: the male-to-female ratio of gastric cancer ranges from 4:1 to 1.5:1 in
      all studies, whereas the prevalence of Hp infection is the same in both sexes;
      the prevalence of Hp infection is as high as 90% in several developing countries
      where the frequency of gastric cancer is very low; the acquisition of the
      infection at a young age, considered very important with regard to the risk for
      cancer, varies from 4.2% to 83% in several countries in which the mortality for
      stomach cancer is approximately 10 in 100,000; and the incidence of cancer in
      patients with a duodenal ulcer is half that of the general population, but Hp
      infects up to 100% of these patients. In the sequence of events that leads to
      gastric cancer, Hp appears to play a role only in the very initial steps, as a
      causative agent of chronic inflammation. The further events that cause gastric
      atrophy, intestinal metaplasia, dysplasia, and cancer are multifactorial,
      involving environmental agents and the host response. It is therefore
      inappropriate to consider Hp a direct carcinogen for humans. This also applies to
      specific strains of the bacterium such as the cagA gene. In fact, Hp infection is
      widespread in humans, and only a small minority will ever be affected by peptic
      ulcer and cancer.

PMID- 9531113
TI  - Radiologic management of hepatolithiasis.
AB  - We describe the diagnostic workup and therapeutic management of patients with
      hepatolithiasis from the viewpoint of the interventional radiologist. The
      diagnosis is best established by direct cholangiography such as percutaneous
      transhepatic cholangiography or endoscopic retrograde cholangiography. We
      consider percutaneous transhepatic stone removal a highly successful, minimally
      invasive, and safe procedure. Access can be gained to the biliary system in
      almost 100% of patients and complete stone clearance through percutaneous
      techniques, including stone fragmentation, removal of stones and fragments by
      baskets, and dilatation of underlying strictures in more than 90%. The role of
      these radiologic techniques is discussed vis-a-vis endoscopic and surgical
      alternatives.

PMID- 9531111
TI  - Esophageal dilation.
AB  - Esophageal dilation, a technique developed four centuries ago, continues to be an
      important method of treating the symptom of dysphagia in patients with luminal
      narrowing of the esophagus. Dilation is safe, with < 0.5% chance of perforation
      and bleeding and a 0.01% risk of death. Mercury bougienage (Maloney dilators),
      hollow polyvinyl dilators (Savary-Guillard), and balloon dilators (Through the
      Scope) are the principal types of dilators in use today. Few trials have compared
      the differing dilating methods. The results of these trials are mixed, and
      further randomized trials are necessary to determine if any technique has
      advantages in efficacy and cost. Although most patients successfully treated with
      dilation suffer with peptic strictures, those with nonpeptic strictures due to
      lower esophageal mucosal rings, corrosive injury, and radiation injury can also
      be treated effectively with dilation. By reviewing the current literature,
      effective treatment algorithms can be used with patients suffering from dysphagia
      due to various types of strictures.

PMID- 9531114
TI  - Chronic pancreatitis: a historical and clinical sketch of the pancreas and
      pancreatitis.
AB  - Chronic pancreatitis (CP), a disease described only in 1946 by Comfort and
      colleagues is currently a global disease. Chronic alcoholism, albeit is the most
      frequent etiologic factor for the disease in most of the affluent nations, a form
      of CP of undetermined etiology, tropical calculous pancreatitis (nutritional
      pancreatitis, Afro-Asian pancreatitis, or tropical calculous pancreatopathy) has
      been recognized to be prevalent in many developing nations. Hereditary
      pancreatitis inherited as an autosomal dominant disease is reported from all
      parts of the world. A landmark is the recent discovery of a gene that transmits
      the disease. Nearly 10% of cases of CP are truly "idiopathic" with no
      identifiable cause. Recent studies indicate that the idiopathic variety of CP has
      two subsets--a juvenile form and a senile or late onset form, with distinct
      clinical features. It is extremely rare to see CP secondary to hyperlipidemia or
      hypercalcemia. These etiologic associations appear to be overemphasized.
      Epidemiological studies indicate that alcoholism is growing in incidence all over
      the world along with an increase in all alcohol-associated disorders such as
      cirrhosis of the liver or pancreatitis. A genetic predisposition to alcoholic
      pancreatitis is suspected based on population studies, but not proven. The
      influence of cigarette smoking in enhancing alcohol-induced injury to the
      pancreas underscores the health hazard associated with alcoholism and cigarette
      smoking--two habits that often coexist in many individuals. The recent finding
      that all forms of CP are premalignant further emphasizes the need to enforce
      preventive measures. The hope is that CP is a preventable disease. The despair is
      that alcoholism is increasing and spreads across geographic and religious
      boundaries.

PMID- 9531115
TI  - Tests of the liver: use and misuse.
AB  - Physicians frequently order batteries of tests that are used to assess liver
      injury or function. These tests are frequently ordered to screen for disease.
      However, a lack of understanding of the nature of the assays and the laboratory
      assignment of normal versus abnormal often leads to unnecessary workup or missed
      disease. We attempt to describe the nature of the most commonly used laboratory
      tests for liver disease, including alanine and aspartate aminotransferases,
      alkaline phosphatase, bilirubin, and gamma glutamyl transpeptidase. In addition,
      the role of functional tests of the liver, including prothrombin time, and
      metabolite clearance tests, such as aminopyrine and monoethylglycinexylidine, are
      examined.

PMID- 9531116
TI  - Role of motility measurements in managing upper gastrointestinal dysfunction.
AB  - Nausea, vomiting, and abdominal pain are common symptoms that suggest many
      diagnoses. The patient's symptoms may be related to an anatomical defect such as
      a peptic ulcer or a mechanical small bowel obstruction. However, no anatomical
      abnormality may be identified despite radiological, endoscopic, or laboratory
      studies. The cause of the patient's symptoms may have significant impact on the
      patient's quality of life (nonulcer dyspepsia) and life span (intestinal pseudo
      obstruction). Abnormal antroduodenal motility may be the underlying cause of the
      patient's symptoms. Normally, coordinated phasic contractions in the stomach and
      small intestine maintain digestion and absorption of food. A prolonged set of
      phasic contractions (phase 3 of the migrating complex) begins in the stomach and
      propagates down the small intestine to excrete nondigestible foods, bacteria, and
      dead cells. Any disturbance in the normal motility pattern can lead to
      maldigestion and symptoms of upper intestinal dysfunction. Objective tests of
      motility disturbances in the stomach and small intestine include measurement of
      gastric emptying, intestinal transit, contractions of the stomach and duodenum,
      and electrogastrography. Abnormal antroduodenal motility may be secondary to an
      abnormality in the smooth muscle (myopathy) or the nerves in controlling smooth
      muscle contractions (neuropathy). Antroduodenal motility measurements may help
      identify a partial small bowel obstruction, the cause of small intestinal
      overgrowth, and the cause of chronic abdominal visceral pain. Motility studies
      may suggest useful drugs for correcting the underlying pathophysiology and
      relieving symptoms.

PMID- 9531117
TI  - Clostridium difficile disease: diagnosis and treatment.
AB  - Clostridium difficile is the most common nosocomial pathogen of the
      gastrointestinal tract. Disease is usually a consequence of antibiotic therapy,
      but sporadic cases do occur. Cytotoxin assay for toxin B remains the gold
      standard for confirming diagnosis. Several rapid enzyme immunoassay tests are
      available, but specificity and sensitivity vary; a negative test may not exclude
      disease. Oral metronidazole 250 to 500 mg four times a day is the recommended
      first-line therapy; vancomycin (125 mg four times a day) should be reserved for
      patients who cannot tolerate metronidazole, who do not respond to this drug, or
      who should not take it for various reasons (i.e., pregnancy). Recurrent C.
      difficile disease is a difficult problem. The nonpathogenic yeast Saccharomyces
      boulardii has been shown in controlled trials to be effective in reducing
      recurrences when given as an adjunct to standard therapy. Prevention of epidemics
      relies on careful hand washing and environmental decontamination.

PMID- 9531118
TI  - Fecal occult blood testing: clinical value and limitations.
AB  - Occult blood in the stool can be detected by chemical (guaiac), heme-porphyrin,
      or immunological methods. Each has advantages and disadvantages, with the guaiac
      slide test Hemoccult II (SmithKline Diagnostics) remaining the most widely used.
      Various technical factors affect its clinical performance, most notably whether
      the slides are rehydrated before processing; hydration increases test sensitivity
      for colorectal cancer but markedly decreases specificity, resulting in a large
      number of false-positive reactions that require invasive and expensive colonic
      workup. Newer immunological tests generally have high sensitivity, but poor
      specificity remains an important problem. In clinical screening situations,
      unhydrated Hemoccult has about 50% sensitivity for colorectal cancers and about
      98% specificity. Only 5% to 10% of positive reactions prove due to cancer,
      however, so the large majority of reactive tests are false positives; this is an
      important weakness of occult blood screening. Slide hydration detects more
      tumors, but the predictive value of a positive test for cancer drops to only
      about 2%, which greatly diminishes the appeal of hydration. Sensitivity of occult
      blood tests for benign colonic polyps is poor, and most polyps found during
      workup of a positive reaction are actually detected by chance because of high
      prevalence in the general population. Controlled clinical trials have now
      documented that periodic occult blood screening produces a relatively small but
      significant mortality benefit from colorectal cancer--about 15% to 18% for
      biennial testing with unhydrated Hemoccult. Aggressive annual screening with
      hydrated Hemoccult may lower mortality by more than 30% but at a very high cost
      because of poor specificity and very low predictive value. Regular occult blood
      testing beginning at age 50 has been endorsed by many professional organizations
      because of the documented mortality benefit, but poor compliance, high costs, and
      ethical uncertainties seriously temper its justification. Whether to implement
      widespread occult blood screening remains a difficult societal decision.

PMID- 9531119
TI  - Refeeding syndrome induced by cautious enteral alimentation of a moderately
      malnourished patient.

PMID- 9531120
TI  - Magnetic resonance cholangiopancreatography: a new technique for evaluating the
      biliary tract and pancreatic duct.
AB  - Magnetic resonance cholangiopancreatography (MRCP) represents a new development
      in MR technology that provides a noninvasive accurate means of evaluating the
      biliary tree and pancreatic duct. Recent technical refinements that allow for
      imaging of the entire biliary tree and pancreatic duct in 18 seconds make this
      examination easily performed even in critically ill patients. The clinical
      applications of MRCP are illustrated in a variety of scenarios that include
      choledocholithiasis, malignant obstruction, incomplete/failed endoscopic
      retrograde cholangiopancreatographies (ERCPs), postsurgical alterations of the
      biliary tract and gastrointestinal tract such as biliary-enteric anastomoses,
      intrahepatic bile duct pathology such as sclerosing cholangitis and AIDS
      cholangiopathy, chronic pancreatitis, congenital anomalies of the biliary tract
      and pancreatic duct, and gallbladder pathology.

PMID- 9531121
TI  - Outcomes research in orthopaedics: health-related quality of life and the SF-36.

PMID- 9531122
TI  - Continuous-flow cold therapy for outpatient anterior cruciate ligament
      reconstruction.
AB  - This prospective, randomized study evaluated continuous-flow cold therapy for
      postoperative pain in outpatient arthroscopic anterior cruciate ligament (ACL)
      reconstructions. In group 1, cold therapy was constant for 3 days then as needed
      in days 4 through 7. Group 2 had no cold therapy. Evaluations and diaries were
      kept at 1, 2, and 8 hours after surgery, and then daily. Pain was assessed using
      the VAS and Likert scales. There were 51 cold and 49 noncold patients included.
      Continuous passive movement (CPM) use averaged 54 hours for cold and 41 hours for
      noncold groups (P=.003). Prone hangs were done for 192 minutes in the cold group
      and 151 minutes in the noncold group. Motion at 1 week averaged 5/88 for the cold
      group and 5/79 the noncold group. The noncold group average visual analog scale
      (VAS) pain and Likert pain scores were always greater than the cold group. The
      noncold group average Vicodin use (Knoll, Mt. Olive, NJ) was always greater than
      the cold group use (P=.001). Continuous-flow cold therapy lowered VAS and Likert
      scores, reduced Vicodin use, increased prone hangs, CPM, and knee flexion.
      Continuous-flow cold therapy is safe and effective for outpatient ACL
      reconstruction reducing pain medication requirements.

PMID- 9531124
TI  - Arthroscopic stabilization of the shoulder for acute primary dislocations using a
      transglenoid suture technique.
AB  - Many studies report the results of arthroscopic stabilization for recurrent
      shoulder instability, with widely variable recurrence rates; however, there are
      very few reports of the use of these techniques in acute first-time dislocations.
      We report the clinical outcomes of 17 patients who had arthroscopic stabilization
      using a transglenoid suture technique for acute primary dislocation. The surgery
      took place between March 1992 and March 1994 and, to date, there has been one
      recurrent dislocation (6%) and no recurrent subluxation. There were no major
      complications, although a number of patients found the knot tied over the
      infraspinatus fascia to be uncomfortable until it resorbed. All patients examined
      had normal power and range of motion, and a clinically stable shoulder. All 16
      patients without recurrence were satisfied with their result. Nine patients
      returned to sports at the same or higher level, including such vigorous contact
      sports as Australian Rules football and rugby. Three patients did not return to
      the same level of sporting activity because of lack of confidence in the shoulder
      or a fear of dislocation despite no clinical evidence of instability. Five
      patients reported a lack of confidence in the shoulder without clinical evidence
      of instability. We suggest that arthroscopic stabilization with transglenoid
      sutures or a suture anchor technique is a reasonable option for the athlete with
      an acute primary shoulder dislocation who wishes to return to sports.

PMID- 9531123
TI  - Arthroscopic partial meniscectomy: a 12-year follow-up and two-step evaluation of
      the long-term course.
AB  - The long-term results after arthroscopic partial meniscectomy of 119 patients
      with a mean follow-up of 12 years are presented in this study. The same series of
      patients had an earlier follow-up 4 years postoperatively. Thus, an evaluation of
      the actual long-term course and not only a single result after partial
      meniscectomy is presented. Arthroscopic partial meniscectomy is shown to be the
      definitive means of therapy for meniscal lesion of the knee joint; 91.7% of
      patients had an excellent or good result 4 years after surgery, and 78.1% rated
      excellent or good 12 years after surgery. Full recovery regarding ability to work
      and sports activity level was achieved in a very high percentage of patients.
      Early results were mostly representative and did not change significantly during
      the long-term course for the isolated meniscal lesion. The factor with the
      highest impact on long-term results was damage to the articular cartilage, which
      did not influence knee function for several years after surgery but became
      increasingly symptomatic over time after 5 years and more. Only 62% of patients
      with additional cartilage damage rated excellent and good 12 years after surgery,
      in contrast with 94.8% good and excellent results in patients with isolated
      meniscal tears. Similar observations were made for the untreated rupture of the
      anterior cruciate ligament.

PMID- 9531125
TI  - The effects of bone plug length and screw diameter on the holding strength of
      bone-tendon-bone grafts.
AB  - The effect of bone plug length and Kurosaka screw (DePuy, Warsaw, IN) diameter on
      graft holding strength of the bone-tendon-bone construct was determined. Random
      length porcine bone plugs were assigned to fixation with 7 or 9 mm Kurosaka
      screws. Peak load to failure was determined. There was a significant decrease in
      peak load to failure of the 5-mm long bone plugs compared with longer bone plugs.
      No difference was found between longer lengths of bone plug in either the 7- or 9
      mm screw diameter groups. The 9-mm diameter screws significantly increased peak
      load to failure for both 1- and 2-cm bone plug lengths.

PMID- 9531126
TI  - Arthroscopic capsular plication for posterior shoulder instability.
AB  - Seventeen patients with recurrent posterior shoulder instability underwent
      posterior capsular plication with or without suture anchors, between 1990 and
      1992. Minimum 2-year follow-up was available for 14 patients (average, 33 months;
      range, 24 to 45 months). The etiology involved trauma in 9 cases, recurrent
      microtrauma in 4 cases, and no trauma in 1 case. Posterior capsular laxity was
      present in all 14 cases and was believed to be the primary pathology, although 12
      patients showed some form of labral pathology. The patients were interviewed and
      assessed in six categories: pain, strength, function, stability, range-of-motion,
      and satisfaction. Twelve patients had excellent results and 2 had fair results.
      Nine of 10 patients who participate in recreational or competitive athletics
      reported full return to their preinjury level of function in their respective
      sports. There was one recurrence of posterior shoulder instability which was
      remedied with a second arthroscopic posterior capsular reconstruction. All 14
      patients were satisfied with the results of their surgery, and no complications
      were noted. Capsular plication is a promising technique in the treatment of
      recurrent posterior shoulder instability.

PMID- 9531127
TI  - Factors affecting isometry of endoscopic anterior cruciate ligament
      reconstruction: the effect of guide offset and rotation.
AB  - Eight normal cadaveric knee specimens were used to evaluate the effects of
      femoral and tibial tunnel positions on length excursions of a single wire and
      bone-patellar tendon-bone graft as measured by an isometer. Femoral attachment
      sites were varied by using a commercially available femoral pin guide with either
      a 5.5- or 7.0-mm offset and by aiming with the guide oriented vertically (12:00
      notch position) or rotating 45 degrees toward the lateral condyle (1:30 or 10:30
      notch position depending on right or left knee). Tibial isometry was altered by
      testing the wire against the posterior tunnel wall or 5-mm anterior using a
      custom centering device. Isometry was measured from 0 degrees to 120 degrees for
      each position tested. A 7-mm offset guide rotated to the 12:00 position yielded
      the best single fiber and graft excursion patterns (P < .05). A 5.5-mm offset
      guide yielded inferior single fiber and graft excursion patterns. Single fiber
      and graft isometry were found to be similar, but not identical in endoscopic
      anterior cruciate ligament reconstruction. Centering the single fiber in the
      tibial tunnel had little effect on excursion patterns, showing that the more
      posterior tibial positions needed for endoscopic reconstruction are acceptable
      from an isometry standpoint.

PMID- 9531128
TI  - Clinical magnetic resonance imaging and arthroscopic findings in knees: a
      comparative prospective study of meniscus anterior cruciate ligament and
      cartilage lesions.
AB  - We compared the diagnostic and predictive value of magnetic resonance imaging
      (MRI) and clinical findings with arthroscopy in 61 knees in a prospective study.
      In meniscal tears, the accuracy and positive predictive value of MRI was found to
      be nearly twice that of clinical examination. The sensitivity, specificity, and
      negative predictive value of MRI were comparable to the figures found in other
      studies. We recommend MRI as a clarifying diagnostic tool when a clinical
      examination indicates a lesion of the meniscus. In our study, the clinical
      relevance of MRI in anterior cruciate ligament lesions and especially in
      cartilage lesions was more doubtful. The combination of clinical and MRI findings
      would reduce the number of blank arthroscopies to 5%. MRI is a valuable
      diagnostic tool in planning the type of anesthesia and treatment, and could
      significantly reduce the need for a second arthroscopy.

PMID- 9531129
TI  - One- and two-incision anterior cruciate ligament reconstruction: a biomechanical
      comparison including the effect of simulated closed-chain exercise.
AB  - The purpose of this study was to evaluate the effect of simulated closed-chain
      exercise on anterior translation in the anterior cruciate ligament (ACL)
      reconstructed knee comparing patellar tendon grafts secured with endoscopic and
      two-incision techniques. ACL reconstructions, were performed on five matched
      pairs of fresh frozen cadaver lower extremities. One of each pair had endoscopic
      (inside-out) placement of the femoral interference screw and other had outside-in
      femoral screw placement. A model for closed-chain exercise was developed to
      simulate half squat exercises using a custom apparatus on the Material Testing
      machine with a 356 N (80 lb) axial load and 40 N (9 lb) static hamstring force.
      Knee motion from near full extension to 60 degrees flexion was achieved by
      varying the quadricep force. One thousand squats were performed, and KT-1000
      arthometry was done before and after cycling each specimen. The femur-graft-tibia
      constructs were then stressed to failure. Closed-chain cycling resulted in no
      significant change in anterior translation in either group. The mean maximum load
      to failure of the femur-graft-tibia construct was 340.4N in the one-incision
      group and 434.2 N in the two-incision group. P=.048 was considered statistically
      significant. Anterior translation did not increase after 1,000 simulated half
      knee bends in either the one- or two-incision groups. Shallow knee bends are an
      important part of aggressive rehabilitation programs, and our data support the
      position that these closed-chain exercises do not deleteriously affect the graft.
      Though the maximum strength to failure differed significantly between the one-
      and two-incision groups, both techniques offered sufficient strength to withstand
      an aggressive simulated rehabilitation protocol.

PMID- 9531130
TI  - Endoscopic release of Achilles peritenon.
AB  - Peritenonitis is the most common cause of achillodynia. When conservative
      treatment fails, surgical decompression of the Achilles tendon (AT) has achieved
      high rates of satisfactory results. The aim of this study was to evaluate an
      alternative endoscopic procedure in Achilles peritenon releasing. We performed
      endoscopy in nine cadaveric limbs. Three 1-cm portal approaches were performed on
      the skin overlying the AT area where a slotted cannula was placed subcutaneously.
      The crural fascia and the peritenon were cut longitudinally using a reverse knife
      while adhesions were freed. After endoscopy, open exposure failed to disclose any
      damage to the sural or calcaneal nerve. Endoscopically, the AT was seen
      throughout its course from the myotendinous junction excepting the distal 2 cm
      where the tendon is normally attached to the skin. Since the crural fascia and
      the Achilles peritenon are readily released by endoscopy in cadaveric specimens,
      findings support this procedure as a valid alternative to treat AT disorders such
      as peritenonitis.

PMID- 9531131
TI  - Failure properties of suture anchors in the glenoid and the effects of cortical
      thickness.
AB  - The ultimate pullout strength and fatigue properties of a screw-design suture
      anchor implanted in the anterior glenoid rim were investigated and compared with
      results from a nonscrew-design suture anchor. Twenty-two cadaveric glenoids were
      harvested and one to two anchors were implanted in the superior and inferior
      quadrants. Fifty-seven Statak 3.5 anchors (Zimmer, Warsaw, IN) were tested and
      compared with results obtained in a previous study on 50 Mitek GII anchors (Mitek
      Products, Inc, Westwood, MA). The specimens were mounted on an Instron fatigue
      testing machine (Instron Corp, Canton, MA) and cycled between preselected minimum
      and maximum loads until pullout. The Mitek GII maintained a higher pullout
      strength than the Statak 3.5 after cyclic loading. Cortical thickness at the
      implantation sites was measured, and found to decrease monotonically from
      superior to inferior positions. The ultimate pullout strength, and subsequently
      the fatigue life, of both types of suture anchors depended directly on cortical
      thickness. The significantly lower performance of both anchors when placed
      inferiorly emphasizes the importance of correct anchor selection, number, and
      placement in this region. All anchors settled during the first 10 to 100 cycles,
      resulting in partial exposure of the implant. Intraoperative cycling of the
      anchors before suture tying may be necessary to achieve complete settling and
      prevent subsequent loss of coaptation between capsule and glenoid. The study
      shows that for the anchors to last 1,000 cycles or more, less than 50% of the
      theoretical ultimate pullout strength should be applied cyclically. With
      aggressive early rehabilitation exercises, this significant decrease in fixation
      strength could shift reconstruction failure from suture breakage or soft tissue
      tearing to anchor pullout.

PMID- 9531132
TI  - Analgesic effects of intra-articular morphine during and after knee arthroscopy:
      a comparison of two methods.
AB  - The objective of this study was to compare the analgesic effects of intra
      articularly administered bupivacaine with bupivacaine/morphine during and after
      therapeutic knee arthroscopy. In a prospective, randomized study, 50 patients
      with clinical signs of medial meniscal injury were allocated to two groups, A and
      B. The patients in group A received 40 mL of 0.25% bupivacaine while the same
      dose of bupivacaine combined with 1 mg of morphine sulphate was administered in
      group B. Pain was estimated using the visual analogue scale (VAS) during surgery
      and at 2, 4, 6, and 24 hours after the operation was completed. Supplementary
      analgesic requirements were also registered, as well as the patients' overall
      rating of the entire procedure. The pain scores were significantly lower in Group
      B throughout the whole postoperative observation period. However, no significant
      differences were found between the two groups in terms of intraoperative pain
      scores, supplementary analgesic requirements, or the overall rating of the
      procedure. This study provides evidence that arthroscopic surgery can be
      performed in a safe manner after intra-articularly administered bupivacaine with
      or without low-dose morphine. The combination of low-dose morphine and
      bupivacaine did, however, produce a superior postoperative analgesic effect
      during the 24 hours following knee arthroscopy compared with bupivacaine alone.

PMID- 9531133
TI  - Revascularization and ligamentization of autogenous anterior cruciate ligament
      grafts in humans.
AB  - Forty-eight patients were enrolled in a study to determine the time interval for
      maturity and remodeling following arthroscopically assisted autogenous anterior
      cruciate ligament reconstruction (ACLR). Two biopsy specimens, one superficial
      and one deep, at the same level in the midsubstance of the ACL were obtained.
      Graft age, time from ACL reconstruction to biopsy, ranged from 3 months to 120
      months. The patients were placed into four groups, (1) 3 to 6 months, (2) 7 to 12
      months, (3) more than 12 months, and (4) control, in accordance with the time
      following ACL reconstruction. Each specimen was independently evaluated using
      light microscopy by two different observers in a blinded design. The biopsy
      specimens were evaluated for vascularity, cellularity, fiber pattern, and
      metaplasia when compared with the normal ACL. None of the patients was protected
      from activity as a result of ligament biopsy and no adverse outcomes were
      reported as a result of biopsy. Our study showed that fiber pattern, cellularity,
      vascularity, and degree of metaplasia obtained gross histological similarity with
      a normal ACL by 12 months after autogenous reconstruction. Unexpectedly, no
      significant statistical differences were noted for all grafts more than 6 months
      after ACLR, for two of the histological features studied, vascularity and fiber
      pattern, P=.05. We conclude that by 12 months after autogenous ACLR, graft
      maturity resembles a normal ACL. Additionally, because no statistical differences
      were noted in vascularity and fiber pattern after 6 months following autogenous
      ACLR, significant graft maturity may occur before 12 months. This may allow early
      postoperative return to full activity and support proponents of accelerated
      rehabilitation programs following autogenous ACLR.

PMID- 9531134
TI  - Radiographic evaluation of anterior cruciate ligament graft failure with special
      reference to tibial tunnel placement.
AB  - Graft failure in anterior cruciate ligament (ACL) reconstruction can result from
      anterior placement of the tibial tunnel. Conventional radiographic evaluation of
      this problem does not take into account potential changes in tibio-femoral
      relationship caused by ACL instability. A retrospective radiographic evaluation
      of failed as well as successful ACL reconstructions was carried out. Both
      published radiographs as well as those obtained of patients treated by the
      authors were evaluated for tibial tunnel placement, roof impingement, and tibial
      position relative to the femur. In the second part of the study, the radiographs
      were obtained under standard conditions in both failed ACL reconstructions and
      normal knees. The results of both parts of the study indicate that lateral
      radiographs of the extended knee with ACL instability are likely to show subtle
      anterior tibial subluxation. The subluxation can give the impression of roof
      impingement on the graft. However, the majority of the failed knees had similar
      tibial tunnel placement compared with successful reconstructions and would appear
      unimpinged once corrected for subluxation. The diagnosis of graft impingement by
      the femoral intercondylar roof has to take into account potential tibial
      subluxation. Impingement as a cause graft failure may be less common than
      previously thought.

PMID- 9531135
TI  - Arthroscopically assisted percutaneous quadricepsplasty: a case report and
      description of a new technique.
AB  - Restricted motion of the knee occurs frequently after an intra-articular fracture
      of the distal femur. Treatment of this complication typically requires open
      release of the quadriceps muscle. To our knowledge an arthroscopically assisted
      method of performing a quadricepsplasty has not been previously described. We
      present such a case and the details of the arthroscopically assisted method that
      may provide an alternative, minimally invasive means of restoring knee flexion in
      the setting of a post-traumatic extension contracture.

PMID- 9531136
TI  - Pretibial cyst formation after anterior cruciate ligament surgery with soft
      tissue autografts.
AB  - Four cases of subcutaneous pretibial ganglion, with direct communication to the
      tibial tunnel after autologous reconstruction of the anterior cruciate ligament
      (ACL) with hamstrings or iliotibial band, are reported. Tibial graft fixation was
      with a staple in three cases, and with a screw and soft tissue washer in one. The
      average time to ganglion development was 44 months, and all occurred more than 2
      years after ACL surgery. At the time of cyst development, no patient had
      subjective or objective knee instability. No patient had evidence of tibial
      tunnel enlargement. All ganglion communicated with the tibial tunnel. This
      communication was shown with magnetic resonance imaging in two cases, which
      showed the origin at the joint. Three patients elected to have the ganglion
      removed; in each of these there was a direct communication with the tibial
      tunnel. Additionally, hardware was removed in all cases, and local autologous
      bone grafting of the tibial tunnel aperture was done in two. Minimum follow-up
      after surgical excision was 2 years, without evidence of recurrence.

PMID- 9531137
TI  - Transsection of the peroneal nerve complicating knee arthroscopy: case report and
      cadaver study.
AB  - We report the case of a 36-year-old male patient who sustained a hyperextension
      trauma of the left knee. After performing diagnostic arthroscopy (partial tear of
      the anterior cruciate ligament) and partial resection of the anterior cruciate
      ligament, the patient experienced a complete paralysis of the peroneal nerve. One
      year after the first surgical procedure, a reconstructive repair of the peroneal
      nerve and a transfer of the anterior tibial muscle was performed. This
      complication is reported for the first time in literature.

PMID- 9531138
TI  - Tibial tunnel bone grafting: a new technique for dealing with graft-tunnel
      mismatch in endoscopic anterior cruciate ligament reconstruction.
AB  - A problem that is frequently encountered during endoscopic anterior cruciate
      ligament reconstruction bone-patellar tendon-bone autograft is that the graft is
      often too long and protrudes from the tibial tunnel. If less than 20 mm of the
      bone plug remains in the tibial tunnel, interference screw fixation cannot safely
      be used, and an alternate form of fixation may have to be employed. A simple
      technique has been developed to deal with this problem. The technique involves
      bone-grafting the tibial tunnel with a cancellous core of bone that is removed
      while creating the tibial tunnel. This not only makes it possible to safely use
      interference screw fixation in all cases, but it also makes it possible to place
      the point of graft fixation very near the anatomic anterior cruciate ligament
      insertion site.

PMID- 9531139
TI  - Direct posterior-posterior triangulation of the knee joint.

PMID- 9531140
TI  - Practices of surgeons in Britain concerning tourniquet use in arthroscopy of the
      knee.

PMID- 9531141
TI  - Incidence of urinary tract infection in patients without bacteriuria undergoing
      SWL: comparison of stone types.
AB  - Extracorporeal shockwave lithotripsy (SWL) currently is accepted as the preferred
      treatment for most renal and upper ureteral calculi. However, little is known
      about the infection risks of SWL. In this study, the incidence and severity of
      urinary tract infection in 117 patients with renal calculi undergoing SWL were
      evaluated and the stone characteristics of those with and without infection were
      compared. The patients were followed clinically and bacteriologically 1 and 14
      days after the procedure. Bacteriuria was noted in six patients within 24 hours
      after SWL. No bacteriuria was noted 2 weeks later. Of these patients, three were
      symptomatic (including dysuria, burning, and fever >38 degrees C). No patient was
      hospitalized. We found no significant correlation between the occurrence of
      bacteriuria and the number or size of the stones (P > 0.05), nor was there any
      correlation between bacteriuria and the stone-free rate or the location of the
      calculi (P > 0.05). However, there was a significantly higher risk of urinary
      tract infection in patients with struvite stones than in those with other types
      of stones (17.3% v 2.1%). In patients with infection stones, prophylactic
      antimicrobial chemotherapy is necessary even if bacteriuria is not present before
      SWL.

PMID- 9531142
TI  - Treatment of staghorn calculi by percutaneous nephrolithotomy and SWL: the Hotel
      Dieu de France experience.
AB  - To evaluate the combined approach of percutaneous nephrolithotomy (PCNL) and
      extracorporeal shockwave lithotripsy (SWL) in the treatment of staghorn calculi,
      we carried out a retrospective review of 101 patients. The stone surface area
      ranged from 654 to 3042 mm2 (1535 mm2 on average). During PCNL, a single access
      tract was used in 22 patients, a double tract in 65 patients, and a triple tract
      in 14 patients. A double-J stent was placed percutaneously in 62 patients.
      Extracorporeal lithotripsy was scheduled at the patient's convenience on an
      outpatient basis approximately 2 weeks after PCNL. The mean hospital stay was 4.4
      days. The combined approach showed a stone-free rate of 67% on the initial
      evaluation, an insignificant residual fragment rate of 26%, and a residual stone
      rate of 7%. With a follow-up of 52 months on average, the global stone growth
      rate was 17%, being 4.4% only among the stone-free group and 27% among the group
      with insignificant residual fragments. The global transfusion rate was 10%.
      Percutaneous stone debulking combined with SWL on an outpatient basis is an
      efficient, minimally invasive treatment for staghorn renal calculi. Reducing the
      number of access tracts, using the flexible nephroscope liberally, and placing a
      double-J stent frequently after PCNL increases the stone-free rate while reducing
      the morbidity and hospital stay.

PMID- 9531144
TI  - Pyelocutaneous fistula after SWL of xanthogranulomatous pyelonephritic kidney:
      case report.
AB  - A 75-year-old woman formed a pyelocutaneous fistula after four extracorporeal
      lithotripsies over 10 months with continued stenting. Xanthogranulomatous
      pyelonephritis was confirmed at nephrectomy. Preprocedure renal function studies
      with culture and eradication of infection are advisable before SWL.

PMID- 9531143
TI  - Redistribution of renal blood flow after SWL evaluated by Gd-DTPA-enhanced
      magnetic resonance imaging.
AB  - Extracorporeal shockwave lithotripsy (SWL) is currently accepted as an effective
      noninvasive treatment for a wide variety of urinary tract calculi. However, the
      bioeffects of high-energy shockwaves on renal parenchyma have yet to be fully
      elucidated. The objective of this study was to measure the acute changes in
      regional renal hemodynamics associated with SWL utilizing dynamic gadolinium-DTPA
      enhanced magnetic resonance imaging (MRI). Seven patients who underwent SWL for
      renal calculi had an MRI study within 4 hours after the treatment. To assess
      renal hemodynamics, a bolus of Gd DTPA (0.03 mmol/kg) was administered, and
      dynamic contrast enhanced images was obtained. Regions of interest (ROI) were
      defined over the cortex and medulla to obtain signal intensity-v-time curves. The
      contralateral kidney in each patient was used as the control. The initial slope
      of the contrast-enhanced signal intensity-v-time curve was used as a measure of
      the perfusion index (PI). In six patients, perfusion imaging showed a consistent
      trend of decreased cortical flow (29+/-8%) and a concomitant increase in
      medullary flow (34+/-14%) in the region of the kidney that was targeted with SWL
      in six patients (86%). This study shows that renal hemodynamics are modified by
      SWL. We hypothesize that this change represents a shunting of flow from cortex to
      medulla in an attempt to prevent ischemia of the medulla.

PMID- 9531145
TI  - Fetotoxicity and teratogenesis of SWL treatment in the rabbit.
AB  - The potential effects of extracorporeal application of shockwaves on an embryo or
      fetus were explored in an animal model. In experimental Series A, the fetuses of
      30 gravid rabbits were exposed to piezoelectrically induced and sonographically
      guided shockwaves on Day 25 or 20 of gestation under technical conditions
      corresponding to extracorporeal lithotripsy in humans. Fetotoxicity was examined
      by abdominal section 24 hours or 9 days later, and immediate/intermediate damage
      was assessed (resorptions, viability, gross injuries, and microscopic lesions of
      the target and neighboring fetuses). In series B, the kidneys of an additional 28
      gravid rabbits (including a control group) were exposed to the same shockwave
      treatment on Day 11 of gestation in order to investigate indirect embryotoxic
      effects, including teratogenic potency. One day before the expected birth, the
      maternal kidneys, uteri, and adjacent organs were examined for lesions, and the
      156 offspring were assessed for embryolethal, embryonoxious, or teratogenic
      sequelae. Shockwave targeting of the cranium, thorax, abdomen, or placenta was
      usually lethal to the fetuses. When the uterine wall or the space between two
      fetuses was targeted, the fetuses suffered from superficial hematoma, as was
      found in the surrounding soft tissues within a radius of 1.5 cm. Fetuses outside
      this region were vital and free of lesions. Shockwave treatment of the maternal
      kidney resulted in renal petechial hemorrhage or subcapsular hematoma. However,
      statistically significant embryotoxic or teratogenetic effects could be
      demonstrated neither from maternal data (resorptions) nor from fetal findings
      (body measurements, vitality test, inner organs, skeletal deformities). When
      using a piezoelectric lithotripter with a small focus of high energy, lesions of
      a fetus are to be expected only when it is located in or close to the focus. It
      seems that embryotoxic or teratogenic sequelae do not occur when shockwaves are
      focused outside the uterus. Nonetheless, this preliminary research does not
      justify clinical use of extracorporeal shockwave lithotripsy in pregnant humans.

PMID- 9531146
TI  - Holmium:YAG laser and its use in the treatment of urolithiasis: our first 160
      cases.
AB  - Over the course of 18 months, 160 patients underwent endoscopic holmium:YAG laser
      surgery at our institution for the treatment of urolithiasis. After appropriate
      consent had been obtained, 127 patients were treated for ureteral calculi, 18 for
      renal calculi, and 15 for large bladder stones. All procedures were performed
      using the VersaPulse combination holmium:YAG/Nd:YAG laser by Coherent Inc., and
      all were done endoscopically using video guidance. Of the 16 patients treated
      percutaneously for renal calculi, 5 were rendered stone free (mean stone size 3.5
      cm). Two patients with renal calculi were treated in a retrograde fashion. One
      had a 1-cm stone in an upper-pole calix with a narrow infundibulum, while the
      other had a stone just proximal to the ureteropelvic junction. Both patients were
      rendered stone free. Of the 127 patients with ureteral calculi, 46 had stents
      placed after fragmentation of their stones. To date, 123 patients in this group
      (97%) are free of stones. All 15 patients with bladder calculi had complete
      fragmentation of their stones. The Ho:YAG laser is effective and versatile in the
      treatment of urolithiasis.

PMID- 9531147
TI  - Simultaneous bilateral percutaneous nephrolithotomy with subarachnoid spinal
      anesthesia.
AB  - We report our experience performing simultaneous bilateral percutaneous
      nephrolithotomy (SBPN) in four patients with large stone burdens in both kidneys.
      We modified the previously described approach by combining SBPN with subarachnoid
      Duramorph (preservative-free morphine sulfate) in an effort to decrease
      postoperative discomfort and shorten the duration of hospitalization. These
      patients (study group) were then compared with a contemporary group of four
      patients with similar bilateral stone burdens who underwent staged bilateral
      percutaneous nephrolithotomies (PCNs) (control group). The comparison showed a
      marked advantage in hospital stay (4.8 days for the study group v 11 days for the
      control group) and postoperative narcotic requirement (27.5 mg of meperidine for
      the study group v 533 mg for the control group). All four patients were rendered
      stone free. This method of treatment for large bilateral renal calculi with the
      addition of subarachnoid Duramorph resulted in less postoperative discomfort,
      less morbidity, and a more rapid recovery than staged PCN or sandwich
      PCN/SWL/PCN.

PMID- 9531148
TI  - Endoscopic management of urolithiasis in the morbidly obese patient.
AB  - A retrospective review of 48 consecutive morbidly obese patients with
      urolithiasis who were treated successfully by endoscopic modalities over 3.5
      years was performed. Of the 73 endoscopic procedures, 48 were ureteroscopic laser
      lithotripsy (UL), 4 were ureteroscopic basket extraction, and 21 were
      percutaneous nephrolithotripsy (PCNL). The patients' weight ranged from 205 to
      385 lbs. (average 286 lbs.). Their abdominal girth ranged from 53 to 65 inches
      (average 59 inches). Twenty-six patients had one procedure, eight patients had
      bilateral procedures, eleven patients had two procedures, and three patients had
      three procedures with utilization of either multiple ureteroscopic treatments or
      the combination of percutaneous and ureteroscopic techniques. The stone-free rate
      after one procedure was 77.8% for UL and 60% for PCNL. The stone-free rate after
      planned repeat procedures was 97% for UL/UL and 89% for PCNL/UL. There were two
      minor complications. Forty-eight procedures were performed on an outpatient
      basis, and the remaining 25 procedures necessitated hospital admission (average
      3.6 days). Morbidly obese patients with urolithiasis who are unable to have SWL
      because of their body weight and abdominal girth can be treated successfully with
      UL, ureteroscopic basket extraction, and PCNL with efficacy comparable to that in
      patients of normal weight and with minimal morbidity. Many renal calculi were
      treated with UL alone with a high success rate.

PMID- 9531149
TI  - New endoureteral double-J stent resists extrinsic ureteral compression.
AB  - The disadvantages of highly flexible endoureteral (double J) stents in the face
      of tumor-induced extrinsic ureteral compression are a consequence of insufficient
      cross-sectional stability, leading to stent compression and thus to
      hydronephrosis or pyonephrosis. The newly developed tumor stent, which is used in
      cases of tumor-induced ureteral compression, is available in sizes from 6F to 8F
      in diameter and 24 to 32 cm in length. The shaft consists of a combination of
      high-stability plastics that presents sufficient elasticity in length. Both ends
      are made of extremely elastic J parts, guaranteeing stable fixation. Compared
      with common double-J stents with the same outside diameter, the tumor stent
      possesses a comparable interior diameter and compared with available stents
      promises sufficient interior flow in the face of extrinsic diseases. The
      application can be undertaken using well-known endoscopic techniques, needs no
      special instrumentation, and entails no learning curve. To date, 49 stents were
      placed at our urologic departments without any problems, the latest stent
      remaining for 15 months. Tumor-induced compression or a higher rate of
      encrustation were not seen. All patients tolerated these stents well. In our
      opinion, the new stabilized endoureteral stent can be seen as a better solution
      than percutaneous nephrostomy or frequent stent changing to tumor-induced
      extrinsic ureteral compression.

PMID- 9531150
TI  - Endoscopic creation of reflux in the pig.
AB  - Vesicoureteral reflux (VUR) in the animal model for experimental purposes can be
      created either by open transvesical or endoscopic techniques. The concept of
      reflux creation is the same for both techniques: incision of the roof of the
      intramural portion of the ureter at the 12 o'clock position. The open method has
      the disadvantages of requiring a cystotomy and a lengthy healing period prior to
      initiating a study, thereby incurring additional expense and the problem of
      introducing several confounding factors. The open method is unreliable because of
      the resolution of reflux over time. Herein, we present a simple transurethral
      endoscopic technique for creating VUR in pigs. This technique was successful in
      producing persistent Grade II or III reflux in 94% of the incised ureters.

PMID- 9531151
TI  - The pig kidney as an endourologic model: anatomic contribution.
AB  - We present detailed anatomic findings on collecting system anatomy and renal
      morphometry in the pig and compare these findings with previous findings in
      humans. We studied three-dimensional polyester resin corrosion endocasts of the
      pelviocaliceal system obtained from 100 kidneys (50 pigs). Eighty kidneys were
      evaluated morphometrically, considering length, cranial pole width, caudal pole
      width, thickness, and weight. The pig collecting system was classified into two
      major groups (A and B). Group A (40%) was composed of kidneys in which the mid
      zone is drained by calices dependent on the cranial or the caudal caliceal group
      or both. Group B (60%) kidneys have the mid-zone drained by calices independent
      of the polar groups. Group B includes two subtypes (B-I and B-II). The pig
      collecting system showed only angles smaller than 90 degrees between the caudal
      (lower) infundibulum and the renal pelvis. Renal morphometric measurements
      revealed the following means: length 11.8 cm, cranial pole width 5.64 cm, caudal
      pole width 5.35 cm, thickness 2.76 cm, and weight 98 g. As in human kidneys, one
      may group the pig collecting system into two groups. Nevertheless, in pigs, we
      did not find a subdivision of Group A. The incidence of collecting systems in
      Groups A and B and the subtypes of Group B in pigs are different from those in
      humans. Also different from humans, in pigs, we found only angles smaller than 90
      degrees between the caudal (lower) infundibulum and the renal pelvis. Except for
      the length, the means of the other morphometric measurements of the pig kidney
      are smaller than those of humans. From an anatomic standpoint, despite the
      differences pointed out, we conclude that the pig kidney is a good animal model
      for endourologic research and training.

PMID- 9531152
TI  - Air travel and thromboembolic complications after percutaneous nephrolithotomy
      for staghorn stone.
AB  - Thromboembolic complications after percutaneous surgery for staghorn stone are
      rare. We report a case of silent deep vein thrombosis (DVT) after long-distance
      air travel that was complicated by both recurrent pulmonary emboli and
      paradoxical arterial embolus despite full-dose systemic heparin anticoagulation.
      Management options for thromboembolic complications in the context of
      percutaneous renal surgery are discussed, and risk factors predisposing to silent
      deep vein thrombosis after long-distance air travel are outlined.

PMID- 9531153
TI  - Laparoscopic staging of bladder tumor: concerns about port site metastases.
AB  - Since the first laparoscopic pelvic lymph node dissection (LPLND) was performed
      for prostate cancer, only one case of port site metastasis has been reported, an
      incidence of 0.1%. On the other hand, three cases of port site metastasis have
      been reported after laparoscopic staging of transitional-cell carcinoma (TCC) of
      the bladder, a reported incidence of almost 4%. Herein, we review the
      circumstances of these three cases and address the potential risk factors and
      possible preventive measures regarding LPLND and port site metastasis in patients
      with TCC of the bladder.

PMID- 9531154
TI  - Laparoscopic suturing and knot tying: the Indian rope trick.
AB  - Laparoscopic suturing and knot tying require a lot of patience and practice and
      can be difficult, time consuming, and frustrating in spite of the advances made
      in the fields of instrumentation, optics, and imaging. The new technique
      described here is an effort to make the procedure simpler by providing
      extracorporeal control of one limb of the suture. It involves percutaneous
      placement of the needle end of the suture in the abdomen and its removal using a
      modified 10 cm long cloth-sewing needle. The part of the suture hanging from the
      abdominal wall helps in the formation and the tying of both the extracorporeal
      and the intracorporeal knots. The extracorporeal knot is just pulled in
      percutaneously to make it intracorporeal and can be tightened easily without a
      knot pusher. The loop for making the intracorporeal knot is formed in one of
      three ways, and the half hitch or the surgeon's knot can be tightened by pulling
      one end extracorporeally and the other intracorporeally. The technique has now
      been used for 36 laparoscopic procedures (8 transperitoneal and 28
      retroperitoneal), including cholestectomy, varicocelectomy, ureterolithotomy,
      pyelolithotomy, pyeloplasty, and nephropexy. Compared with the conventional
      method of laparoscopic suturing and knot tying, it was found to be easier to
      learn.

PMID- 9531155
TI  - High-frequency electrosurgery using the microcomputer-controlled Erbe ICC 350
      unit.
AB  - To quantitate electrosurgical and tissue variables during transurethral prostatic
      resection and electrovaporization, these procedures were performed in five
      patients using standard endoscopic equipment and the Erbe ICC 350 electrosurgical
      generator. Current, voltage, power, and resistance were monitored continuously.
      Energy transfer was quantitated during each electrode pass. Prostatic resection
      or electrovaporization was successful in each patient. Current, voltage,
      resistance, and power were similar during resection and electrovaporization,
      whereas energy transfer was greater during electrovaporization. Generator and
      tissue characteristics can now be precisely monitored and instantaneously altered
      during transurethral prostatic electrosurgery to minimize energy transfer to the
      patient while producing the desired tissue effects.

PMID- 9531156
TI  - Stationary mechanical-assist technology for single-surgeon laparoscopic bilateral
      varicocelectomy.
AB  - One potential detraction from the continued application of laparoscopy in the
      management of varicoceles is the requirement for a skilled assistant, which
      increases the cost of performing this surgery. This report describes the clinical
      application of a simple stationary mechanical-assist device to allow a single
      surgeon to perform bilateral varicocelectomies. The device is attached to the
      surgical table with a rotary adjusting stem-arm. A cross-mounted sidearm
      stretches over the patient and forms the attachment to the friction-jointed elbow
      and wrist attachment to the laparoscope, providing the range of motions similar
      to a human arm (shoulder, elbow, and wrist). By adjusting the tension at all
      three levels, changes of the laparoscopic camera portal are possible. Both of the
      surgeon's hands are then free to work through two operating trocars. The
      Laprotract arm (Minnesota Scientific, St. Paul, MN) costs $3000 and is
      autoclavable for quick reutilization. The average time needed to set up the
      device for bilateral varicocelectomy during eight cases was 2 minutes. The mean
      procedure time was 65.0 (+/-23.1) minutes, reflecting its ease of use. The
      electronic image obtained from the stationary mechanical assistant was always
      steady, and there was no inadvertent wandering from the surgical field.
      Statistical comparison with 63 open left and 22 open bilateral varicocelectomies
      during the same time period demonstrated no significant differences in the
      procedural times. Mechanical-assist technologies can facilitate laparoscopic
      bilateral varicocelectomies, allowing a single surgeon to perform this operation
      as quickly as left and bilateral open procedures.

PMID- 9531157
TI  - The "Wedge" resection device for electrosurgical transurethral prostatectomy.
AB  - The "Wedge" (Microvasive, Natick MA) is a new electroresection device for
      transurethral prostatectomy (TURP) using the standard resectoscope. The design,
      which is broader than the standard loop and thickens from front to back, results
      in better hemostasis when used at 275 to 300 W because of its ability to cut and
      coagulate tissue simultaneously. In the canine model, histologic examination
      demonstrated a 2-mm zone of coagulation around the chips and in the resection
      bed; this response was not observed in the specimens resected by the standard
      tungsten loop. No adjacent tissue damage was found with either the Wedge or the
      loop, and the temperatures recorded at the capsule rose only 4 degrees C
      regardless of the device used. In the 65 patients treated, the average hematocrit
      drop on postoperative Day 1 was 3.0%, and serum sodium was unchanged. One year
      postoperatively, the peak flow rate had increased by 101%, and the AUA Symptom
      Score was 6.1. The only surgical complication was urethral strictures (3%)
      necessitating incision. Most striking was the increased case of resection
      attributable to improved intraoperative vision. The data suggest that Wedge TURP
      is as safe and efficacious as standard loop TURP. The surgical field is markedly
      improved and clear because of intraoperative hemostasis. A TURP can be performed
      with a view toward minimizing patient morbidity and increasing surgical ease.

PMID- 9531158
TI  - Echo-guided SWL of vesical stones with Dornier MPL 9000 lithotripter in
      obstructed and unobstructed patients.
AB  - Sixty-one patients with vesical stones (38 with underlying obstructive conditions
      and 23 unobstructed) underwent SWL using ultrasound targeting under no regional
      or general anesthesia. A foley catheter was not routinely employed, and the
      bladder was filled in a physiologic way. Complete resolution was obtained in 47
      patients (78%); in particular, 66% of the obstructed patients and 96% of the
      unobstructed patients became stone free in one to four SWL sessions. The average
      number of sessions for all patients was 1.28+/-0.63. Fragments were completely
      evacuated also in some patients with severe obstruction and in all three patients
      with neurogenic bladder dysfunction. The size and number of stones did not seem
      to play a limiting role in SWL effectiveness: the principal limiting factor was
      the hardness of the stone. No severe complications occurred. However, in six
      patients (10%), some fragments stopped in the urethra, causing acute urine
      retention, and endoscopic extraction was necessary. Echo-guided SWL of bladder
      stones is safe and highly effective in nonobstructed patients and can be
      considered the elective monotherapy method. In obstructed patients, SWL efficacy
      is lower, but the method may be suggested for patients who refuse or delay other,
      more invasive techniques.

PMID- 9531159
TI  - Role of T cells in atopic dermatitis. New aspects on the dynamics of cytokine
      production and the contribution of bacterial superantigens.
AB  - Atopic dermatitis (AD) is a chronically relapsing inflammatory skin disease.
      Influx of activated T cells into the skin lesions represents a hallmark in AD.
      Recent results indicate a dynamic T-cell-derived cytokine production in AD. In
      addition to the well-known TH-2 component, chronic lesions and late-phase
      allergic responses are characterized by an TH-1/TH-0 cytokine pattern. Although
      there is no doubt that aeroallergens can contribute to the elicitation of acute-
      and late-phase allergic responses in AD, their role in the immunopathogenesis is
      controversally discussed. Recent attention has been given to the long-known
      phenomenon of persistent colonization of AD skin with S. aureus and the potential
      role of S. aureus-derived superantigens. Evidence from several in vitro and in
      vivo studies suggests that such bacterial superantigens have the potency to
      trigger chronic T-cell-mediated skin inflammation. Although these data are
      certainly suggestive, further clinical studies are required to elucidate the role
      of bacterial superantigens in initiation, maintenance and, especially, chronicity
      of skin inflammation.

PMID- 9531160
TI  - The Th1/Th2 paradigm and experimental murine leishmaniasis.
AB  - In recent years, the Th1/Th2 concept has become of prime importance in the
      understanding of heterogeneous responses of the immune system and implications
      thereof for infectious and autoimmune diseases. Originally established on the
      basis of different cytokines produced by T cell clones, it is now known that the
      Th1/Th2 concept really defines totally different immune pathways that affect most
      if not all cells of the immune system. Murine experimental leishmaniasis was the
      first model to confirm the relevance of the Th1/Th2 concept in vivo. Herein, we
      summarize the current knowledge on the characteristics and generation of Th1 and
      Th2 cells, as well as on recent advances of the application of this concept to
      murine cutaneous leishmaniasis.

PMID- 9531162
TI  - Differential endothelial adhesion molecule expression in early and late whealing
      reactions.
AB  - In order to clarify the pathomechanisms of fleeting versus more persistent
      wheals, expression of endothelial adhesion molecules was studied in biopsies of
      lesional and uninvolved skin of 15 patients with different types of whealing
      reactions, using immunohistochemistry. In wheals of < or = 30 min duration, no
      increase of ELAM-1 and ICAM-1 was noted. GMP-140 expression was absent in prick
      tests, but could be demonstrated in lesions of cholinergic and cold urticaria,
      with a gradual increase of the latter with time. In wheals of > or = 6 h
      duration, GMP-140 was only weakly expressed whereas ELAM-1 and ICAM-1 were
      markedly up-regulated in lesional and less so in nonlesional skin of acute,
      chronic recurrent and delayed pressure urticaria. This differential expression of
      endothelial adhesion molecules may reflect the activity of mast cell-derived and
      other mediators during the elicitation phase and explains the persistence of
      wheals in different types of urticaria.

PMID- 9531161
TI  - Receptor-mediated maternofetal transfer of immunoglobulins. Inhibition of
      transport of anti-HIV-1 immunoglobulin by generic immunoglobulins in the in vitro
      perfused placenta.
AB  - OBJECTIVES: The passage of immunoglobulin G (IgG) across the placenta is thought
      to involve Fc' receptors on the syncytiotrophoblast. To confirm the receptor
      dependency of this process we have studied the changes in the tissue content and
      transfer kinetics of immunoglobulins and hyperimmune serum to HIV (HIVIG) during
      in vitro dual placental perfusion. METHODS: Isolated lobules of term placentae
      from normal pregnancies were perfused in a model of maternal and fetal
      circulation. The perfused tissue was compared to fresh tissue samples from the
      same placenta for the content of IgG, IgG subclasses, IgM, cytokeratin, human
      placental lactogen and SP1 antigen by immunohistochemistry and by protein
      elution. RESULTS: The immunoglobulin staining faded by an average of 40% during
      the 1st hour of perfusion. In contrast, staining for cytokeratin, human placental
      lactogen and SP1 remained unchanged. During a 4-hour recycling of endogenous
      immunoglobulins in the maternal circulation, IgG and HIVIG crossed to the fetal
      side in a steady rate. The transport of HIVIG could be inhibited by preperfusion
      with an intravenous gammaglobulin preparation (IVIG). DISCUSSION: The transfer of
      IgG across the placenta occurs in a steady state rate consistent with a receptor
      mediated mechanism. Furthermore, inhibition of HIVIG maternofetal transfer by
      IVIG further establishes the receptor-mediated transfer of immunoglobulins
      through the placenta.

PMID- 9531163
TI  - Alternative G1m, G2m and G3m allotypes of IGHG genes correlate with atopic and
      nonatopic pathways of immune regulation in children with bronchial asthma.
AB  - Most genetic studies of bronchial asthma deal with IgE responsiveness. The manner
      by which allergens trigger IgE production and activate mast cells suggests that
      several genetic loci may be involved. Several reports of candidate genes include
      chromosome 6 and HLA antigens, chromosome 14q11 and the alpha chain of the T cell
      receptor, chromosome 11q32 and the beta chain of the high-affinity IgE receptor
      and chromosome 5 and the gene cluster for IL-4, respectively. In addition, the
      immunoglobulin heavy chain G (IGHG) genes on chromosome 14q32 have been
      associated with both atopic and non atopic bronchial asthma in children. In order
      to further investigate the role of IGHG genes in asthmatic children, the
      phenotypes of patients with homozygous but alternative IGHG genes were
      investigated. IGHG gene expression of patients with childhood asthma was
      determined by serum Gm allotypes with a quantitative competitive indirect ELISA
      method. The groups consisted of 24 children with the homozygous G3m(b/b)-G1m(f/f)
      G2m(n/n) and 16 with the alternative G3m(g/g)-G1m(a/a)-G2m(-n/-n) genes. The two
      different genotypes were investigated for serum IgE (PRIST), serum IgG subclass
      levels (radial immunodiffusion), Gm allotype levels (competitive ELISA), IgA and
      IgM levels (radial immunodiffusion), peripheral blood eosinophils, specific IgE
      antibodies (skin prick test, SPT, or radioallergosorbent test, RAST), number of
      peripheral blood CD lymphocyte markers (flow cytometry) and serum IL-4 and IFN
      gamma levels (ELISA). Comparison of the two genotypes in children with bronchial
      asthma revealed significantly increased IgE (p < 0.001), increased specific IgE
      (p < 0.001), as investigated by SPT or RAST (n = 10 allergens tested), increased
      number of peripheral blood eosinophils (p < 0.01), increased serum IgG1(f/f)(p <
      0.001), IgG2(n/n) (p < 0.001) and IgG3(b/b)(p < 0.01) levels, and decreased CD8
      given in percent of the total number of peripheral lymphocytes, (p < 0.02) in the
      G3m(b/b)-G1m(f/f)-G2m(n/n) genotype. The asthmatic children with the G3m(g/g)
      G1m(a/a)-G2m(-n/-n) genes instead showed low IgE levels, practically no specific
      IgE antibodies, a lower number of peripheral blood eosinophils, lower IgG1(a/a),
      IgG2(-n/-n) and IgG3(g/g) serum levels and higher CD8 lymphocyte numbers. The
      results show that the IGHG3(b/b)-IGHG1(f/f)-IGHG2(n/n) genes are in linkage
      disequilibrium with allergen-specific high-responding IGHE genes and present the
      atopic phenotype of bronchial asthma, while the IGHG3(g/g)-IGHG1(a/a)-IGHG2(-n/
      n) genes present the nonatopic phenotype of childhood asthma. The two genotypes
      with different amino acid epitopes of their constant heavy gamma1, gamma2 and
      gamma3 chains presented qualitatively different IgG1, IgG2 and IgG3 molecules,
      respectively, and also different serum IgG1, IgG2 and IgG3 levels, together with
      different numbers of peripheral blood eosinophils and CD8 lymphocytes. The two
      IGHG genotypes represent different pathways of human immune regulation. An
      association of atopic IGHG genotype with other candidate genes for atopy could be
      suggested.

PMID- 9531164
TI  - Expression of histamine receptors in nasal epithelial cells and endothelial cells
      -the effects of sex hormones.
AB  - BACKGROUND: Hyperreactivity of the nasal mucosa is a characteristic of nasal
      allergy. During pregnancy, aggravation of nasal allergic symptoms is occasionally
      observed in subjects with nasal allergy. METHODS: Using the reverse transcription
      polymerase chain reaction and Southern blot hybridization method, we investigated
      histamine H1 receptor mRNA (H1R mRNA) expressions in specimens of nasal
      epithelial layer obtained by scraping, as well as cultured human nasal epithelial
      cells (HNECs) and human mucosal microvascular endothelial cells (HMMECs). We
      compared the expressions on the specimens from patients with nasal allergy with
      those with nonallergic rhinitis or those from normal volunteers. In addition, we
      investigated the effects of female hormones on the H1R mRNA expressions in HNECs
      and HMMECs. RESULTS: H1R mRNA was detected in scraped specimens of nasal
      epithelial layer, as well as in HNECs and HMMECs. The mRNA expressions in nasal
      mucosal scraped specimens of epithelial layers and HNECs were more marked in
      patients with nasal allergy than in the other two groups. In addition, the
      present study demonstrates that the female hormones beta-estradiol and
      progesterone significantly increase the expressions of H1R mRNA on HNECs and
      HMMECs. CONCLUSION: The increase of the expressions of H1R mRNA may explain, in
      part, the nasal hyperreactivity to histamine observed in patients with nasal
      allergy. It has also been suggested that sex hormones are related to the
      preponderance of females in the incidence of allergic rhinitis after puberty, and
      that they are related, at least partially, to the aggravation of the nasal
      hyperreactivity symptoms during pregnancy through the enhanced expression of H1R
      mRNA on HNECs and HMMECs.

PMID- 9531165
TI  - Experimental study for the development of an in vitro test for contact allergens.
      2. Comparison of the in vitro sensitization test with the guinea pig maximization
      test for contact allergens.
AB  - We have previously reported an in vitro hapten-specific sensitization method
      using Pam-212 cells (in vitro sensitization test) to identify the potential
      effectiveness of contact allergens. In the present study, we conducted comparison
      studies of 11 allergens and 2 irritants in order to evaluate the method as an
      alternative predictive test. The guinea pig maximization test (GPMT) was
      developed based on the test described by Magnusson and Kligman. Our assay was
      carried out as follows: we treated Pam-212 cells with 13 test chemical solutions,
      while T cells and macrophages of BALB/c mice were cultured with hapten-conjugated
      Pam-212 cells for 5 days. After incubation, 10(5) T cells were stimulated with
      mitomycin-C-treated spleen cells conjugated with chemicals. Three days later, the
      [3H]methyl thymidine incorporation was counted. The results of the GPMT were in
      agreement with those reported in previous studies except for benzocaine. In our
      GPMT experiments, benzocaine was negative, but it had been classified as a
      moderate sensitizer in previous studies. Our assay detected extreme, strong and
      moderate sensitizers as previously classified by the GPMT They could be
      summarized as follows: three of five chemicals classified as moderate
      sensitizers, and 100% of strong or extreme sensitizers were detected by both the
      GPMT and the in vitro sensitization test. No irritants showed a positive reaction
      in our assay. These results support the view that the sensitivity of our in vitro
      test may be equivalent to that of the GPMT and may be useful as a rapid and
      objective allergen screening test.

PMID- 9531166
TI  - Specificity of the human IgE response to the different purified caseins in
      allergy to cow's milk proteins.
AB  - BACKGROUND: Cow's milk is one of the most frequent food allergens. Whole casein
      appears to be highly allergenic. It corresponds to an association of four
      different proteins, alpha(s1)-, alpha(s2)-, beta- and kappa-caseins in
      approximate proportions of 40, 10, 40, and 10%, respectively. METHODS: These
      different components were thus purified and used as immobilized antigens in an
      original enzyme immunoassay to measure specific serum IgE response in a
      population of 58 children (median age 11 months) allergic to cow's milk who were
      sensitive to whole casein. RESULTS: A great variability was observed in the
      affinity and specificity of specific IgE responses in milk-allergic patients'
      sera. 85% of the patients presented IgE against each of the four caseins.
      Statistically higher amounts of specific IgE were found to be directed against
      the most abundant fractions (alpha[s1]- and beta-casein). Co- and/or cross
      sensitization to the different caseins were seen in most of the patients
      sensitive to whole casein. CONCLUSION: These results suggest that both distinct
      and common epitopes may occur on these different caseins. The major site of
      phosphorylation which is the most conserved domain in three caseins could be
      involved in the IgE response to casein and in immunocross-reactivity between
      these proteins.

PMID- 9531167
TI  - Expression and rapid purification of an Aedes aegypti salivary allergen by a
      baculovirus system.
AB  - Mosquito salivary proteins cause allergic reactions in humans. Recombinant
      salivary allergens will facilitate both the diagnosis and immunotherapy of
      mosquito allergy. The Aed a 1, a 68-kD apyrase in the saliva of Aedes aegypti,
      has been demonstrated to be an allergen which binds to the IgE of mosquito
      allergic subjects. The baculovirus expression vector pBlueBacHis C equipped with
      an N-terminal histidine tag was used to express the Aed a 1 protein. The cDNA
      coding for the 3' significant portion of Aed a 1 (Aed a 1 3') (150-562 amino acid
      residues) was cloned into pBlueBacHis C. The rAed a 1 3' protein expressed by
      recombinant baculovirus was verified by immunoblot using anti-Aed a 1 and anti
      histidine antibodies, respectively. The histidine-tagged fusion protein was
      purified to apparent homogeneity from infected Sf9 cells by Ni2+ resin affinity
      chromatography. Both immunoblot and ELISA showed that the purified rAed a 1 3'
      binds to the IgE and IgG in mosquito allergic sera, indicating that the
      antigenicity of the rAed a 1 3' is identical to the native Aed a 1 of Aedes
      aegypti saliva.

PMID- 9531168
TI  - Images in allergy and immunology. Structure and epitopes of Chi t 1.01.

PMID- 9531170
TI  - Present state of dialysis and transplantation in Pakistan.

PMID- 9531169
TI  - Exposure to parakeets and bronchiolitis obliterans.
AB  - Case report of a 64-year-old woman with increasing dyspnea and cough. She cared
      at home for 8 parakeets (Melopsittacus undulatus). Subsequent studies revealed a
      restrictive pulmonary defect and transbronchial biopsy, a histological
      bronchiolitis obliterans (BO). No significant elevated anti-avian IgG could be
      detected, probably because of a transient hypogammaglobulinaemia. The implication
      of antigenic exposure to avian antigens in the pathogenesis of BO is discussed.

PMID- 9531171
TI  - Mesangiolysis: an update.
AB  - Mesangiolysis occurs in many renal diseases, both human and experimental. At
      least three types of mesangiolysis may be recognized, which differ in their mode
      of origin and in morphologic features. The first type is severe mesangiolysis
      with formation of glomerular cysts and subsequent cellular proliferation
      resembling glomerulonephritis. In the second type, mesangiolysis is associated
      with extensive widening of the subendothelial space and is thought to follow
      endothelial injury. The third type is mesangiolysis with lamellated mesangial
      nodules which is believed to result from relatively mild but persistent or
      recurrent localized mesangial, and perhaps also endothelial damage, with lysis of
      mesangial anchor points.

PMID- 9531172
TI  - Nephrologists as primary care providers: a review of the issues.
AB  - Considering the role of nephrologists as primary care providers for their chronic
      dialysis patients requires exploration of a number of factors. These factors
      include the definition of a primary care provider, the time and expertise needed
      to provide primary care, the expectations of nephrologists and dialysis patients
      who give and receive primary care, the appropriate preventive care for end-stage
      renal disease (ESRD) patients, and the current and future roles of nephrologists
      within a changing health care environment. Unfortunately, few studies have
      addressed these issues, and there is little objective information on which to
      base guidelines and recommendations about nephrologist-directed primary care of
      ESRD patients. Most nephrologists spend a significant portion (30% to 35%) of
      their time caring for dialysis patients, and 90% report providing primary care to
      dialysis patients. Most dialysis patients view their nephrologist as their
      primary care provider. The increasingly aged and ill ESRD population will
      undoubtedly necessitate additional time and expertise for care from an
      understaffed nephrology work force. The increased use of advanced practice nurses
      and alliances with health care delivery systems under global capitation programs
      may develop into effective strategies to provide care for an increasing
      population of dialysis patients. The nonnephrologic health care needs, including
      specific and appropriate cancer screening and preventive health care protocols
      for ESRD patients whose life expectancies are significantly less than the general
      population, are unclear. The issues involved in considering nephrologists as
      primary caregivers for ESRD patients include these and other related factors, and
      will be discussed in this review.

PMID- 9531173
TI  - Improving the care of patients treated with hemodialysis: a report from the
      Health Care Financing Administration's ESRD Core Indicators Project.
AB  - To determine the impact of a quality improvement intervention on dialysis care
      delivered to hemodialysis patients, we studied 213 hemodialysis facilities in
      North Carolina, South Carolina, and Georgia. Dialysis adequacy measurements made
      on two random samples of 30 patients per treatment center, or all patients if
      fewer than 30 were treated, selected in October 1994 (preintervention) and
      October 1995 (postintervention) were used to estimate the facility mean urea
      reduction ratio (URR) and the proportion of patients with a mean URR less than
      50%. The 10% of facilities (n = 22) with the highest proportion of patients with
      a mean URR less than 50% in the facility at preintervention were selected for an
      intervention that included feedback of facility-specific mean URR, educational
      programs, a quality improvement workshop, and monitoring until improvement was
      attained. Changes between preintervention and postintervention facility mean URR
      and proportions of patients with a URR less than 60% and 65% were used to assess
      the impact of the intervention. After 1 year, the mean URR had increased an
      average of 7% in intervention centers compared with an increase of 1.4% (P <
      0.001) in the remainder of the treatment centers in the Network. There was an
      average reduction of 17.2% in the proportion of patients with a URR less than 65%
      in intervention centers compared with 4.8% in the other facilities (P < 0.001).
      Comparable reductions in the proportion of patients with a mean URR of less than
      60% were 16.2% in intervention centers and 2.0% in comparison facilities (P <
      0.001). After controlling for facility case mix and other characteristics, the
      intervention was independently associated with an absolute 2.4% increase in
      facility-specific mean URR. We conclude that the intervention was associated with
      improvement in hemodialysis care.

PMID- 9531174
TI  - Barriers to adequate delivery of hemodialysis.
AB  - Mortality rates among American hemodialysis patients are the highest in the
      industrialized world. Measures of delivered dialysis (Kt/V) correspond strongly
      with survival and are estimated to be inadequate in one third of patients. We
      sought to determine the importance of potential barriers to adequate dialysis,
      including patient-related and technical factors. Using a cross-sectional study
      design, we abstracted the charts of 721 randomly selected patients from all 22
      chronic hemodialysis units in northeast Ohio. For each of 1,836 treatments
      provided to these patients, we assessed delivered dialysis (Kt/V) and patient
      related factors (ie, hypotension, intradialytic symptoms, and treatment time
      missed due to noncompliance or transportation problems) and technical factors
      (ie, dialysis prescription, type of vascular access, clotting, and dialyzer
      reuse). We used hierarchical regression analysis to determine which potential
      barriers were independently related to delivered dialysis after adjustment for
      patient demographic and medical characteristics. Barriers independently related
      to dialysis delivery (all P values < 0.001) included patient noncompliance,
      present in 3% of treatments; low dialysis prescription, 14%; use of a catheter
      for vascular access, 11%; and clotting, 1%. The prevalence of identified barriers
      varied dramatically across facilities (eg, the prevalence of low dialysis
      prescription ranged from 0% to 37%, while the prevalence of catheter use ranged
      from 3% to 28%). In conclusion, patient noncompliance, low dialysis prescription,
      catheter use, and clotting are the most important barriers to dialysis delivery.
      Further work is needed to develop interventions to overcome these barriers and to
      determine the effect of such interventions on dialysis adequacy and patient
      survival.

PMID- 9531175
TI  - Determinants of heart rate variability in chronic hemodialysis patients.
AB  - To clarify determinants of heart rate variability in hemodialysis patients, we
      evaluated 187 patients receiving chronic hemodialysis. Ambulatory
      electrocardiogram was recorded for 24 hours from the beginning of hemodialysis.
      Standard deviation of the normal RR interval (SDNN) was used as a marker of heart
      rate variability. Multiple regression analysis was performed to select
      independent variables associated with SDNN from the following 14 variables: age,
      sex, body mass index before hemodialysis, presence of ischemic heart disease,
      diabetic nephropathy as primary renal disease, smoking, duration of hemodialysis,
      mean blood pressure before hemodialysis, left ventricular mass index and fraction
      shortening in echocardiography, use of beta blockers, use of angiotensin
      converting enzyme inhibitors, hematocrit, and blood urea nitrogen. Older age (P <
      0.0001), presence of diabetic nephropathy as primary renal disease (P < 0.0001),
      lower hematocrit (P = 0.0121), larger body mass index before hemodialysis (P =
      0.0133), longer duration of hemodialysis (P = 0.0200), and smoking (P = 0.0350)
      were associated with reduced SDNN. In hemodialysis patients, SDNN as a marker of
      cardiac autonomic modulation was associated with hematocrit, body mass index, and
      duration of hemodialysis, in addition to previously reported variables.

PMID- 9531176
TI  - Association of serum phosphorus and calcium x phosphate product with mortality
      risk in chronic hemodialysis patients: a national study.
AB  - Elevated serum phosphorus is a predictable accompaniment of end-stage renal
      disease (ESRD) in the absence of dietary phosphate restriction or supplemental
      phosphate binders. The consequences of hyperphosphatemia include the development
      and progression of secondary hyperparathyroidism and a predisposition to
      metastatic calcification when the product of serum calcium and phosphorus (Ca x
      PO4) is elevated. Both of these conditions may contribute to the substantial
      morbidity and mortality seen in patients with ESRD. We have analyzed the
      distribution of serum phosphorus in two large national, random, cross-sectional
      samples of hemodialysis patients who have been receiving dialysis for at least 1
      year. Data were obtained from two special studies of the United States Renal Data
      System, the Case Mix Adequacy Study (1990) and the Dialysis Morbidity and
      Mortality Study Wave 1 (1993). The relative risk of death by serum phosphorus
      quintiles is described after adjusting for age at onset of ESRD, race, sex,
      smoking status, and the presence of diabetes, the acquired immunodeficiency
      syndrome, and/or neoplasm. Logistic regression analysis is then used to describe
      the demographic, comorbid, and laboratory parameters associated with high serum
      phosphorus. Serum phosphorus was similar in these two study populations and
      averaged 6.2 mg/dL. Ten percent of patients had levels greater than 9 mg/dL and
      at least 30% of each group had serum phosphorus levels greater than 7 mg/dL. The
      adjusted relative risk of death by serum phosphorus level was not uniform across
      all quintiles, being constant below a level of 6.5 mg/dL and increasing
      significantly above this level. The relative risk of death for those with a serum
      phosphorus greater than 6.5 mg/dL was 1.27 relative to those with a serum
      phosphorus of 2.4 to 6.5 mg/dL. This increased risk was not diminished by
      statistical adjustment for coexisting medical conditions, delivered dose of
      dialysis, nutritional parameters, or markers of noncompliance. Evaluation of
      predictors of serum phosphorus greater than 6.5 mg/dL revealed in multivariate
      analysis that younger age at onset of ESRD, female sex, white race, diabetes,
      active smoking, and higher serum creatinine levels were all significant
      predictors. Analysis of serum calcium revealed no correlation with relative risk
      of death. The Ca x PO4 product, however, showed a mortality risk trend similar to
      that seen with serum phosphorus alone. Those in the highest quintile of the Ca x
      PO4 product (>72 mg2/dL2) had a relative mortality risk of 1.34 relative to those
      with products of 42 to 52 mg2/dL2. The relative mortality risk by log parathyroid
      hormone (PTH) level was elevated for patients with higher levels, but the
      mortality risk associated with hyperphosphatemia was independent of PTH. For
      hemodialysis patients who have been receiving dialysis for at least 1 year, we
      conclude that a large percentage have a serum phosphorus level above 6.5 mg/dL
      and that this places them at increased risk of death. This increased risk is
      independent of PTH. The mechanism(s) responsible for death is unknown, but may be
      related to an abnormally high Ca x PO4 product. Although mechanisms are not
      clearly established, this study supports the need for vigorous control of
      hyperphosphatemia to improve patient survival.

PMID- 9531177
TI  - Equal levels of blood pressure control in ESRD patients receiving high-efficiency
      hemodialysis and conventional hemodialysis.
AB  - The present study compared the status of hypertension and adequacy of blood
      pressure control in 73 end-stage renal disease (ESRD) patients treated with four
      different modalities of hemodialysis, namely, conventional hemodialysis (CHD)
      with cuprophan 1.1 m2 at a blood flow rate of 300 mL/min, high-efficiency
      hemodialysis (HED) with cuprophan 1.6 m2 at a blood flow rate of 450 to 500
      mL/min, high-flux hemodialysis (HFD) with F80 polysulfone 1.8 m2 at a blood flow
      rate 500 mL/min, and high-flux hemodiafiltration (HDF) with F80 2 x 1.8 m2 in
      series at a blood flow rate of 600 to 650 mL/min. Thirty of the 73 patients (41%)
      were receiving one or more antihypertensive agents to control their hypertension.
      The percentage of patients taking antihypertensive medication was less in the
      groups treated with HED, HFD, and HDF compared with the CHD group: 38%, 39%, and
      39%, respectively, in the HED, HFD, and HDF groups versus 56% in the CHD group.
      Control of systolic and diastolic hypertension was achieved in a higher
      percentage of patients treated with HED, HFD, and HDF compared with patients
      treated with CHD. Sixty-two percent of HED, 58% of HFD, and 61% of HDF patients
      compared with 44% of CHD patients had systolic blood pressure less than 150 mm
      Hg, whereas 77% of HED, 76% of HFD, and 78% of HDF patients compared 56% of CHD
      patients had diastolic blood pressure less than 90 mm Hg. However, the
      differences in the use of antihypertensive medication and control rates of
      hypertension did not reach statistical significance. The average blood pressure
      of all patients was 144/89 mm Hg; this did not differ significantly between the
      four groups. There also were no significant differences in etiology of ESRD,
      hematocrit, biochemical data, as well as use and dose of recombinant human
      erythropoietin between the four groups. Compared with the CHD patients, the
      average treatment times with high-efficiency treatments were shorter, with HDF
      patients showing the shortest mean treatment time of 157+/-41 minutes per
      hemodialysis session. The mean Kt/V was higher in the groups treated with HED,
      HFD, or HDF (1.31+/-0.3, 1.30+/-0.4, and 1.43+/-0.3, respectively) than in the
      CHD group (1.12+/-0.3; P < 0.05). Interdialytic weight gain also did not differ
      among the four groups. There was no correlation between predialysis mean arterial
      pressure and either treatment time (r = 0.04, P = NS), Kt/V (r = 0.03, P = NS),
      ultrafiltration rate (r = 0.06, P = NS), or interdialytic weight gain (r= -0.08,
      P = NS). There also was no significant association between Kt/V and use of
      antihypertensive medications (chi-square = 1.76, P = NS). There was, however, a
      significant positive correlation between interdialytic weight gain and treatment
      time (r = 0.33, P < 0.01). We conclude that the use of short dialysis sessions
      with efficient hemodialysis treatments, namely, HFD and HDF, was associated with
      similar levels of blood pressure control in ESRD patients.

PMID- 9531178
TI  - Effect of sertraline hydrochloride on dialysis hypotension.
AB  - Hemodialysis hypotension (HH) is a very common disorder and has a multifactorial
      etiology. Autonomic dysfunction occurs in up to 50% of patients with end-stage
      renal disease (ESRD) and plays a key role in HH in some patients. Sertraline
      hydrochloride, a central nervous system serotonin reuptake inhibitor, has been
      shown to be an effective treatment of hypotension caused by autonomic dysfunction
      in disorders such as neurocardiogenic syncope and idiopathic orthostatic
      hypotension. This study sought to determine whether sertraline was effective in
      ameliorating HH. A retrospective chart analysis was performed that included nine
      consecutive patients (aged > or = 54 years, time on hemodialysis > or = 2.2
      years) placed on sertraline (50 to 100 mg/d) for depression who also had HH
      (defined as prehemodialysis systolic blood pressure [SBP] < or = 100 mm Hg, > or
      = 40 mm Hg decrease in SBP during hemodialysis, SBP <90 mm Hg, any diastolic
      blood pressure <40 mm Hg, or a decrease in blood pressure-causing symptoms)
      before treatment with sertraline. The data from a 6-week pre-sertraline period
      were compared with the data from a 6-week sertraline period (defined as 6 weeks
      after drug begun). Blood pressure medications were unchanged during the trial
      period of sertraline. However, nadir mean arterial pressure recorded during a
      given dialysis session in the pre-sertraline period (55+/-4 mm Hg) was
      significantly lower than that recorded in the sertraline period (68+/-5 mm Hg; P
      < 0.05). In addition, the number of hypotensive episodes (same definition as HH)
      per dialysis session during the sertraline period was significantly lower than
      that during the pre-sertraline period (mean, 0.6+/-0.2 episodes per session v
      1.4+/-0.3 episodes per session; P < 0.005). The number of therapeutic
      interventions required for hypotension during the sertraline period was also
      significantly less than that during the pre-sertraline period (mean, 1.7+/-0.8
      interventions v 11.0+/-3.0 interventions; P < 0.005). The urea reduction ratio
      (62.7%+/-4.7% v 63.1%+/-9.3%; P = NS) and hematocrit (28.9%+/-0.8% v 29.5%+/
      1.0%; P = NS) did not change significantly. It is concluded that the short-term
      (6 weeks) use of sertraline hydrochloride reduces HH in some patients with ESRD.
      A possible mechanism for this effect is sertraline-induced attenuation of the
      paradoxical sympathetic withdrawal that may underlie HH in some patients with
      ESRD.

PMID- 9531179
TI  - Cardiovascular response to submaximal stationary cycling during hemodialysis.
AB  - Exercise intolerance is a problem in renal failure. Stationary cycle training
      during hemodialysis treatment is recommended as safe, effective, and practical,
      but requires compensations for both exercise and acute changes in uremia. Eight
      patients pedalled for 5 minutes, at 60% of VO2peak, at 0, 1, 2, and 3 hours of a
      hemodialysis treatment. Fluid removed, blood pressure, cardiac output, heart
      rate, O2 uptake, hematocrit, and arterial O2 content were measured. Mean arterial
      blood pressure, systemic vascular resistance, stroke volume, (a-v)O2 difference,
      and mixed-venous O2 content were calculated. Fluid removed was 1,356 mL/hr (P <
      0.002 for each hour), but with no significant cardiovascular effects during the
      first 2 hours. At 3 hours, decreasing cardiac output, stroke volume, and mean
      arterial pressure all reached significance at rest (P < 0.05), and five of eight
      patients could not exercise. We conclude that the cardiovascular exercise
      response is superimposed on hemodynamic effects of dialysis and is adequately
      stable during the first 2 hours of treatment. After 2 hours, cardiovascular
      decompensation may preclude exercise.

PMID- 9531180
TI  - Prediction of equilibrated postdialysis BUN by an artificial neural network in
      high-efficiency hemodialysis.
AB  - In urea kinetic modeling, postdialysis blood urea nitrogen (BUN) is usually
      underestimated with an overestimation of the Kt/V especially in high-efficiency
      hemodialysis (HD). Thus, an artificial neural network (ANN) was used to predict
      the equilibrated BUN (Ceq) and equilibrated Kt/V (eKt/V60) by using both
      predialysis, postdialysis, and low-flow postdialysis BUN. The results were
      compared to a Smye formula to predict Ceq and a Daugirdas' formula (eKt/V30) to
      predict eKt/V60. Seventy-four patients on high-efficiency or high-flux HD were
      recruited. Their mean urea rebound was 28.6+/-2%. Patients were divided into a
      "training" set (n = 40) and a validation set (n = 34) for the ANN. Their status
      was exchanged later, and the two results were pooled. In the prediction of Ceq,
      both Smye formula and low-flow ANN were equally highly accurate. In patients with
      a high urea rebound (>30%), although Smye formula lost its accuracy, low-flow ANN
      remained accurate. In the prediction of eKt/V60, both Daugirdas' formula and low
      flow ANN were equally accurate, although the Smye formula was not so accurate. In
      patients with a high urea rebound, although both Smye and Daugirdas' formulas
      lost their accuracy, low-flow ANN remained accurate. We concluded that low-flow
      ANN can accurately predict both Ceq and eKt/V60 regardless of the degree of urea
      rebound.

PMID- 9531181
TI  - Acquisition of hepatitis C virus in hemodialysis patients: a prospective study by
      branched DNA signal amplification assay.
AB  - Serological data indicate that hepatitis C virus (HCV) infection is very common
      among chronic hemodialysis (HD) patients. Circumstantial evidence suggests that
      hemodialysis per se is an important risk factor for this infection. We used a
      novel methodology, the branched DNA (bDNA) signal amplification assay, which is
      capable of detecting HCV RNA and of quantifying HCV viral load in serum, to
      prospectively determine the rate of acquisition of HCV infection in 274 anti-HCV
      negative patients undergoing HD treatment in four hemodialysis units. Moreover,
      we used bDNA testing to analyze the dynamics of HCV acquisition among HD
      patients, a high-risk group for HCV infection with immune compromise conferred
      from uremia. Two patients were identified with de novo acquisition during 1 year
      of prospective bDNA testing. Thus, the HCV incidence was 0.73% per year. De novo
      acquisition of HCV infection was observed in the absence of identifiable
      parenteral risk factors. Both patients showed the same pattern of HCV
      acquisition: they underwent an initial viremic phase that was associated with an
      increase in alanine transaminase (ALT) activity and that preceded the anti-HCV
      seroconversion. This was followed by HCV RNA clearance and normalization of ALT
      activity. Anti-HCV positivity occurred 1 and 2 months after the ALT increase in
      the first and second patients, respectively. Although HCV incidence was low
      (0.73%), further research is warranted to set the optimal policy for eliminating
      the risk of nosocomial transmission of HCV in the HD setting. Our findings show
      the pattern of HCV acquisition in chronic HD patients and emphasize the need to
      screen the HD population for ALT measurement combined with anti-HCV testing for
      detecting hepatitis C. HCV RNA testing can identify HCV before seroconversion in
      individuals with deranged liver function tests. The acquisition of HCV in HD
      patients without identifiable risk is confirmed.

PMID- 9531182
TI  - Plasma leptin level and its relationship with body composition in hemodialysis
      patients.
AB  - Leptin is a newly found hormone secreted by adipocytes that regulates food
      intake, thermogenesis, and body fat. We measured plasma leptin levels in 103
      patients with chronic renal failure treated by hemodialysis and 167 age- and
      gender-matched healthy control subjects to examine the impact of renal failure on
      plasma leptin levels and the influence of leptin on body composition measured by
      dual-energy X-ray absorptiometry. Hemodialysis patients showed a significant
      decrease in both body fat mass and lean body mass compared with those of the
      control subjects. Plasma leptin was significantly elevated in the hemodialysis
      group over the controls. In both groups, leptin was higher in female than male
      subjects, and it correlated positively with percent body fat. The subjects were
      divided into six categories according to percent body fat, and plasma leptin
      levels were compared between the two groups in the same category. Leptin of
      hemodialysis patients was significantly higher than that of the control subjects
      in the percent body fat categories of 30 or greater, whereas there was no
      statistically significant difference in leptin concentrations in the lower
      percent body fat categories. This was also true in the comparison in each gender,
      and leptin levels in female subjects showed a more remarkable difference between
      the hemodialysis and control groups in obese categories. Multiple regression
      analysis in all subjects indicated that plasma leptin levels were independently
      affected by percent body fat, plasma insulin concentration, gender, and renal
      failure. The positive impact of renal failure on leptin remained significant in
      the subjects with percent body fat of 30 or greater in the multiple regression
      model, whereas it was no longer significant in the remaining lean subjects. In
      multiple regression analysis of factors affecting fat mass index and lean mass
      index, leptin level was selectively associated with fat mass index, but not with
      lean mass index, regardless of percent body fat ranges. These results indicate
      that renal failure is an important factor affecting plasma leptin levels,
      especially in obese female subjects, and that hyperleptinemia was closely related
      to fat mass but not to lean body mass in hemodialysis patients.

PMID- 9531183
TI  - Reducing a peritoneal dialysis program's cost by changing from a vendor-provided
      to a program-provided system for general medical supplies: significant savings in
      CCPD.
AB  - An examination of the costs associated with outpatient chronic peritoneal
      dialysis prompted us to investigate the charges for general medical supplies used
      by patients on continuous ambulatory peritoneal dialysis (CAPD) and continuous
      cycling peritoneal dialysis (CCPD) in our hospital-owned, not-for-profit
      peritoneal dialysis program. The items used by patients to perform their dialysis
      exchanges and daily exit site care included 4 x 3 and 2 x 2 sterile gauze pads,
      antibacterial soap, masks, tape, and betadine swabsticks. The charges for these
      supplies when purchased from the dialysis vendor were compared with charges for
      the same items if purchased directly from hospital stores by the peritoneal
      dialysis program and then distributed to the patients. This initial analysis
      suggested a considerable savings if the peritoneal dialysis program provided the
      supplies. Based on this estimated savings, in July 1995, the peritoneal dialysis
      program changed from a vendor-provided to a program-provided system for general
      supplies used by CAPD and CCPD patients. This study examined the differences in
      charges expressed as $/patient-month for two periods: July 1994 to June 1995
      (when all general medical supplies were provided by dialysis vendors directly to
      the CAPD and CCPD patients) and July 1995 to May 1996 (when the peritoneal
      dialysis program purchased general medical supplies from hospital stores and
      distributed these supplies directly to the patients). The median vendor charges
      for CAPD patients (n = 21 during 1994 to 1995 and n = 18 during 1995 to 1996)
      were not significantly different between the two periods. In fact, the charges
      were slightly higher during the 1995 to 1996 period ($1,264/patient-month v
      $1,193/patient-month during the vendor-provided period of July 1994 to June 1995,
      P = 0.67). The median vendor charges for patients on CCPD were significantly
      lower during the 1995 to 1996 period when the peritoneal dialysis program
      provided the general medical supplies used for CCPD ($1,110/patient-month v
      $1,389/patient-month during 1994 to 1995, P = 0.003). There were 30 CCPD patients
      during the 1994 to 1995 period and 27 patients on CCPD during 1995 to 1996. The
      total charges for CAPD and CCPD patients combined included dialysis vendor
      charges (dialysis solution, tubing, cycler rental) and charges from hospital
      stores. These total charges were lower in the July 1995 to May 1996 period when
      general medical supplies were purchased directly from hospital stores rather than
      from the dialysis vendors: $1,201/patient-month versus $1,360/patient-month (P =
      0.03). The median hospital store charges rose slightly during the July 1995 to
      May 1996 period when supplies were purchased by the peritoneal dialysis program
      from hospital stores ($31/patient-month v $21/patient-month, P = 0.37, during the
      July 1994 to June 1995 period when general medical supplies were purchased
      directly from dialysis vendors). However, despite the rise in charges from
      hospital stores, an overall savings of $149/patient-month was achieved when the
      peritoneal dialysis program purchased and provided general medical supplies used
      by the peritoneal dialysis patients. This $149/patient-month equals $1,788
      savings per dialysis year for each patient on peritoneal dialysis for that year.
      Significant savings in the cost of a chronic peritoneal dialysis program may
      therefore occur if less expensive sources for the general medical supplies used
      by CAPD and, especially, CCPD patients are found.

PMID- 9531184
TI  - Apolipoprotein E4 reduces risk of diabetic nephropathy in patients with NIDDM.
AB  - Hypercholesterolemia is a major determinant of the decline of renal function in
      patients with diabetes. Apolipoprotein E polymorphism may influence the
      metabolism of lipoprotein in diabetic patients. The purpose of this study was to
      investigate the association between genetic polymorphisms in apolipoprotein E and
      the progression of diabetic nephropathy in patients with non-insulin-dependent
      diabetes mellitus over a 10-year period (13 to 37 years; median, 20 years).
      Subjects with a stable renal function without overt proteinuria had a higher
      cholesterol level, lower incidences of hypertension and proliferative diabetic
      retinopathy, and a higher frequency of the E4 allele than subjects with a decline
      in renal function (end-stage renal failure requiring dialysis treatment). In the
      diabetic patients, the apolipoprotein E4 carriers had a higher cholesterol level
      than did the noncarriers. The survival rate from renal disease in the
      apolipoprotein E4 carriers was higher than in the noncarriers among the diabetic
      patients. Apolipoprotein E polymorphism and hypertension were identified as
      independent risk factors for the progression to renal failure. Results indicate
      that apolipoprotein E polymorphism is associated with the progression of diabetic
      nephropathy. Presence of the apolipoprotein E4 allele is a protective factor, and
      other alleles are risk factors.

PMID- 9531185
TI  - Prospective study of atrial natriuretic peptide for the prevention of
      radiocontrast-induced nephropathy.
AB  - Radiocontrast-induced nephropathy (RCIN) is a common cause of hospital-acquired
      acute renal failure and is associated with a high mortality rate. RCIN is
      potentially preventable, because administration of the radiocontrast agent is
      predictable, and a high-risk population has been identified. This multicenter,
      prospective, randomized, double-blind, placebo-controlled trial was performed to
      evaluate the efficacy of intravenous atrial natriuretic peptide (anaritide, ANP 4
      28) to prevent RCIN. Patients with stable chronic renal failure (serum creatinine
      greater than 1.8 mg/dL or serum creatinine between 1.5 and 1.8 mg/dL with
      estimated creatinine clearance of < or = 65 mL/min) were assigned to receive
      either placebo or one of three doses of anaritide (0.01 microg/kg/min, 0.05
      microg/kg/min, or 0.1 microg/kg/min) for 30 minutes before and continuing for 30
      minutes after radiocontrast administration. All patients were given intravenous
      0.45% saline for 12 hours before the radiocontrast procedure and continuing for
      12 hours after the last dose of radiocontrast. Both ionic and nonionic
      radiocontrast agents were administered. RCIN was defined as either an absolute
      increase of serum creatinine of > or = 0.5 mg/dL or a percent increase of > or =
      25% over baseline. Of the 247 patients who completed the study, 50% had diabetes
      mellitus. There were no statistical differences in baseline serum creatinine,
      change in serum creatinine, or the incidence of RCIN. The incidence of RCIN was
      placebo, 19%; anaritide (0.01), 23%; anaritide (0.05), 23%; anaritide (0.1), 25%.
      Patients with diabetes mellitus had a significantly greater incidence of RCIN:
      placebo, 26% versus 9%; anaritide (0.01), 33% versus 13%; anaritide (0.05), 26%
      versus 21%; anaritide (0.1), 39% versus 8% (diabetic v nondiabetic, P < 0.002).
      There was no effect in the diabetic or nondiabetic groups by anaritide on the
      incidence of RCIN. Comparison of the highest-risk group of patients, defined as
      patients with diabetes mellitus and a baseline serum creatinine > or = 1.8 mg/dL,
      with the lowest-risk group, defined as patients without diabetes mellitus and a
      baseline serum creatinine of 1.8 mg/dL or less, did not show a beneficial effect
      of anaritide administration. In conclusion, administration of intravenous
      anaritide before and during a radiocontrast study did not reduce the incidence of
      RCIN in patients with preexisting chronic renal failure, with or without diabetes
      mellitus.

PMID- 9531186
TI  - Treatment of membranous lupus nephritis.
AB  - In this study, we retrospectively analyzed the effects of treatment in 19
      patients with membranous lupus nephritis (MLN) and nephrotic syndrome. Eight
      patients were treated with corticosteroids alone, and the other 11 patients
      received methylprednisolone and chlorambucil alternated every other month for 6
      months. At presentation, sex, age, duration of renal disease before renal biopsy,
      plasma creatinine, and arterial hypertension were similar in the two study
      groups. Of the eight patients treated with corticosteroids alone, three showed
      complete remission and one partial remission of the nephrotic syndrome. During
      the follow-up (mean, 114+/-63 months), seven of these eight patients developed
      one or more renal flare-ups. Of the 11 patients treated with methylprednisolone
      and chlorambucil, seven had complete remission, and the other four had partial
      remission of the nephrotic syndrome. During the follow-up (mean, 83+/-59 months),
      only one patient had renal flare-up. At the end of the follow-up, all patients
      were alive, but three patients in the group treated with corticosteroids alone
      had developed a doubling of plasma creatinine, and another patient had persistent
      nephrotic syndrome. Two other patients were in complete remission, one patient
      was in partial remission, and the last patient had nonnephrotic proteinuria. In
      the group of patients treated with methylprednisolone and chlorambucil, one
      patient developed extracapillary glomerulonephritis and eventually entered end
      stage renal failure 24 years after the clinical onset of renal disease. Seven
      patients were in complete remission, and three patients were in partial remission
      at the last follow-up visit. This retrospective study suggests that
      methylprednisolone and chlorambucil may induce a more stable remission of
      nephrotic syndrome and may better protect renal function in the long term in
      comparison with corticosteroids alone. However, these results must be confirmed
      by a prospective controlled trial.

PMID- 9531187
TI  - Renal concentration of alpha-tocopherol: dependence on gender and lack of effect
      on polycystic kidney disease in Han:SPRD rats.
AB  - A gender-associated dimorphism, with males being more severely affected than
      females, has been observed in autosomal dominant polycystic kidney disease,
      acquired renal cystic disease, and the renal cystic disease of the Han:SPRD rat.
      A recent study has suggested that gonadal hormones may be responsible for this
      dimorphism. Because gonadal hormones have an effect on the concentration of alpha
      tocopherol in the liver and adrenal glands and because recent studies indicate
      that oxidative stress may be important in the pathogenesis of polycystic kidney
      disease, we wanted to determine whether the renal concentration of alpha
      tocopherol is higher in female than in male rats and whether this difference
      accounts for the gender dimorphism of polycystic kidney disease in Han:SPRD rats.
      At 3 weeks of age, male and female heterozygous cystic (cy/+) rats were divided
      into three groups fed a vitamin E-deficient diet or the same diet supplemented
      with either 65 IU or 10,000 IU alpha-tocopherol/kg laboratory chow. At 8 weeks of
      age, blood samples and kidneys were obtained for determinations of plasma
      creatinine and urea, renal concentration of alpha-tocopherol and glutathione,
      kidney weights, and histomorphometric analysis. Female rats had higher renal
      concentrations of alpha-tocopherol and less severe renal cystic disease, as
      reflected by plasma creatinine and urea values, kidney weight corrected by body
      weight, and histomorphometric analysis, than male rats. The difference in renal
      alpha-tocopherol concentration, however, could not account for the different
      severity of the renal cystic disease, because depletion or enrichment of vitamin
      E in the diet had marked effects on the renal concentration of alpha-tocopherol
      without affecting the severity of the renal cystic disease. Cy/+ rats had higher
      renal concentrations of alpha-tocopherol than +/+ animals, possibly reflecting a
      disturbance of redox metabolism associated with polycystic kidney disease. Renal
      concentrations of glutathione were unaffected by the vitamin E content of the
      diet. Although these results do not support the use of vitamin E in the treatment
      of polycystic kidney disease, observations in the Han:SPRD rat may or may not be
      relevant to human polycystic kidney disease.

PMID- 9531188
TI  - Brachial plexus compression due to subclavian pseudoaneurysm from cannulation of
      jugular vein hemodialysis catheter.
AB  - Jugular venous cannulation is generally safer than subclavian cannulation. The
      traumatic complications associated with jugular vein hemodialysis catheters are
      rare. A jugular vein, therefore, has become the preferred site for hemodialysis
      catheter insertion. We describe the first case of brachial plexus compression
      attributable to delayed recognition of a right subclavian pseudoaneurysm as a
      complication of jugular venous cannulation of hemodialysis catheter. We advocate
      that any neck swelling, new bruit, and the symptoms of brachial plexopathy after
      jugular venous cannulation warrant an intensive investigation to exclude arterial
      injury. Because delayed diagnosis may lead to a worsened prognosis in patients
      with brachial plexus palsy, physicians should exercise vigilance to detect and
      manage early the potentially serious and fatal complications of subclavian artery
      pseudoaneurysm and brachial nerve injury.

PMID- 9531190
TI  - Simultaneous development of Kaposi's sarcoma and lymphoma in a renal transplant
      recipient.
AB  - Kaposi's sarcoma (KS) and non-Hodgkin's lymphoma are frequent complications of
      renal transplantation that usually occur as separate entities. We describe a
      young woman who simultaneously developed Kaposi's sarcoma and lymphoma after
      kidney transplantation. Immunosuppression consisted of cyclosporine and
      prednisone with normal serum creatinine. Fifteen months after transplantation,
      she developed Kaposi's sarcoma skin lesions, generalized lymphadenopathy, and
      ascites. A lymph node biopsy showed both Kaposi's sarcoma and lymphoma in the
      same tissue specimen with Epstein-Barr viral genomes within the tumor cells.
      Graft function remained normal. Cyclosporine was discontinued, and treatment with
      acyclovir was started, but the patient's condition rapidly deteriorated, and she
      died. This is the first case in which both Kaposi's sarcoma and lymphoma were
      present in the same biopsy specimen. After renal transplantation, more than one
      tumor can develop either simultaneously or in succession.

PMID- 9531189
TI  - Diagnosis and radioablation treatment of toxic multinodular goiter in a
      hemodialysis patient.
AB  - Toxic multinodular goiter is rare in hemodialysis patients. In addition,
      establishing the diagnosis of hyperthyroidism in the elderly patient with renal
      failure is difficult because abnormal thyroid function tests can erroneously be
      attributed to euthyroid sick syndrome. Treatment of hyperthyroidism in dialysis
      patients by radioiodine ablation involves careful calculation of 131I dose,
      determination of interval between 131I administration and its removal by
      hemodialysis, and minimization of radiation hazards during dialytic removal of
      131I. We described the clinical presentation of an elderly dialysis patient with
      toxic multinodular goiter and discussed our diagnostic and therapeutic
      approaches. The patient's recovery after 131I ablation was complete and
      uneventful.

PMID- 9531191
TI  - Ciprofloxacin overdose: acute renal failure with prominent apoptotic changes.
AB  - Acute renal failure due to ciprofloxacin has been well described. The previously
      reported cases have been consistent both clinically and pathologically with
      tubulointerstitial nephritis (TIN). We report a case of ciprofloxacin overdose
      leading to acute renal failure characterized by acute tubular necrosis (ATN). The
      outstanding features in the patient's renal biopsy were those of distal nephron
      apoptosis, best seen in plastic-embedded sections and electron microscopy. This
      report shows that the distal nephron can be singularly involved in acute renal
      failure and that electron microscopy or plastic-embedded sections may be
      necessary to define its involvement.

PMID- 9531192
TI  - Successful treatment of IgA nephropathy in association with low-grade B-cell
      lymphoma of the mucosa-associated lymphoid tissue type.
AB  - Kidney and the urogenital tract are among the various mucosal sites involved in
      mucosa-associated lymphoid tissue (MALT) lymphoma. We report a case with
      simultaneous onset of crescentic immunoglobulin (Ig) A nephropathy and
      gastrointestinal low-grade B-cell lymphoma of the MALT type with kidney
      infiltration. M-component of IgM lambda was detected in the serum, and the renal
      biopsy specimen showed monotypic lambda light chain staining in the lymphoma
      cells but not the glomeruli. The heavy proteinuria and impaired creatinine
      clearance returned to normal, and microscopic hematuria disappeared 20 months
      after treatment with chlorambucil as single-agent chemotherapy. This coincided
      with a complete resolution of the gastric and renal lymphoma infiltration. The
      close association of both the onset and successful outcome of the two entities
      thus support their possible causal relationship, and we discuss the possibility
      of an association of the disturbance of the MALT by the lymphoma cells with the
      pathogenesis of IgA nephropathy.

PMID- 9531193
TI  - Early treatment with ACE inhibition may benefit HIV-associated nephropathy
      patients.

PMID- 9531194
TI  - Nephrotic syndrome in a young postpartum woman.

PMID- 9531195
TI  - Dual 1,25-dihydroxyvitamin D3 signal response pathways in osteoblasts: cross-talk
      between genomic and membrane-initiated pathways.
AB  - Osteoblasts are key regulatory cells in the control of systemic calcium ion
      (Ca2+) homeostasis. They, along with cells in the kidney and intestine, function
      as an integral part of the vitamin D endocrine system. The hormonally active form
      of vitamin D, 1,25-dihydroxyvitamin D3 (1,25[OH]2D3), interacts with osteoblasts
      at several levels to modulate their phenotype and function. The interactions
      involve distinct receptor systems that operate on unique time scales. Rapid
      nongenomic actions (milliseconds to minutes), mediated through membrane receptor
      systems, do not require protein synthesis and include activation of voltage
      sensitive Ca2+ channels, induction of phospholipid and sphingolipid turnover,
      elevation of intracellular Ca2+ concentrations, priming of parathyroid hormone
      (PTH)-sensitive ion channels, and activation of second messenger systems. In the
      longer term (many hours to days), interactions mediated through binding of
      1,25(OH)2D3 to nuclear receptors, present in mature osteoblasts, modulate
      transcription of target genes. Target genes for 1,25(OH)2D3 including those
      encoding for the bone matrix proteins osteopontin (OPN) and osteocalcin (OCN),
      possess vitamin D response elements (VDRE) upstream of the transcriptional start
      site. In addition, it is now clear that a number of intermediate effects (1 to 3
      hours) also occur. These effects require longer times than the aforementioned
      rapid effects, but precede the long-term consequences of activation of nuclear
      receptors. These include alterations in the phosphorylation state of various
      proteins secreted by osteoblasts, including OPN, attributable to
      activation/inactivation of various intracellular protein kinases and
      phosphatases. Intermediate effects are likely to involve both membrane-initiated
      rapid actions and transcriptional effects on early genes that do not require the
      nuclear receptor for 1,25(OH)2D3. These intermediate effects, therefore,
      represent ideal targets for the study of the interaction or "cross-talk" between
      rapid membrane-initiated, nongenomic effects and nuclear receptor-mediated,
      genomic effects of 1,25(OH)2D3 on osteoblasts. Intermediate effects also invite
      the study of rapid, non-nuclear receptor-mediated genomic effects of 1,25(OH)2D3
      on osteoblasts. Complete understanding of the mechanisms by which 1,25(OH)2D3
      exerts its pleiotropic effects on osteoblasts and other target cells,
      contributing to control of Ca2+ homeostasis, requires integration of the concepts
      learned from studies of both rapid and long-term pathways.

PMID- 9531196
TI  - The principle of utility in cost-based contemporary medical care.

PMID- 9531197
TI  - Demand-based assessment of workforce requirements for orthopaedic services.
AB  - On the basis of an analysis of the supply of and demand for orthopaedic surgeons,
      we projected that there will be 21,134 full-time-equivalent orthopaedists in the
      year 2010 if training continues at current levels. We estimated a demand-based
      requirement of 17,012 full-time-equivalent orthopaedic surgeons, indicating a
      surplus of 4122 full-time equivalents. In terms of orthopaedist-to-population
      ratios, we estimated that there will be 7.5 full-time-equivalent orthopaedists
      per 100,000 population in 2010 compared with a demand-based requirement of 6.0
      full-time equivalents. However, we did not include estimates of the demand for
      orthopaedic surgeons as assistants in the operating room in our model. If an
      assistant orthopaedic surgeon is required for all procedures, an additional 3906
      full-time-equivalent orthopaedists would be demanded, thus eliminating the
      surplus. The demand for an assistant orthopaedic surgeon in only half of the
      procedures would still lead to a sizable reduction in the surplus.

PMID- 9531198
TI  - The orthopaedic workforce: which rate is right?

PMID- 9531199
TI  - The utility of histological examination of tissue removed during elective joint
      replacement. A preliminary assessment.
AB  - The utility of histological examination of tissue removed during elective joint
      replacement has not been determined. During a one-year period, tissue removed
      during 168 total joint replacements was submitted for histological examination.
      The clinical and histological diagnoses, the cost of the histological study, and
      the clinical course were determined for all joints. Degenerative joint disease,
      rheumatoid arthritis, and avascular necrosis accounted for 98 per cent of the
      histological diagnoses. There were sixteen discrepancies between the clinical and
      histological diagnoses. The histological diagnosis did not affect the treatment
      of fifteen of these joints. However, the treatment was altered for one joint that
      had a clinical diagnosis of degenerative joint disease and a histological
      diagnosis of osteomyelitis; on review, the initial histological diagnosis was
      determined to be incorrect. In 1996 dollars, the cost of histological examination
      for all 168 joints was $10,698.24. Although there would be considerable cost
      savings on a population basis if histological examination were not performed,
      this savings must be weighed against the effect of a misdiagnosis on the
      management of a particular patient.

PMID- 9531201
TI  - A randomized, prospective study of operative and non-operative treatment of
      injuries of the fibular collateral ligaments of the ankle.
AB  - One hundred and forty-six adults who had an isolated injury of the fibular
      collateral ligaments of the ankle were randomized to be managed operatively or
      non-operatively. Disruption of the ligaments was diagnosed by means of a physical
      examination and on the basis of stress radiographs of the ankle made with use of
      a specially designed device to hold the leg. Operative treatment, performed in
      seventy-three patients, consisted of suture repair of the disrupted ligaments
      within seventy-two hours after the injury, followed by immobilization of the
      ankle in a below-the-knee plaster cast for six weeks. Non-operative treatment,
      used for seventy-three patients, consisted of the use of an ankle orthosis for
      six weeks. After a minimum of two years of follow-up, we could detect no
      significant differences, with the numbers available, between the two groups with
      regard to the functional result or the degree of joint laxity that was evident on
      stress radiographs. The non-operative group lost a mean of 1.6 weeks from work,
      and the operative group lost a mean of 7.0 weeks. We concluded that non-operative
      treatment of an injury of the fibular collateral ligaments of the ankle yields
      results that are comparable with those of operative repair and is associated with
      a shorter period of recovery.

PMID- 9531200
TI  - One-stage treatment of congenital dislocation of the hip in children three to ten
      years old. Functional and radiographic results.
AB  - We reviewed the results of operative treatment of congenital dislocation of the
      hip in eighteen children (twenty-five hips) whose average age at the time of the
      index operation was six years and four months (range, three years to nine years
      and eleven months). None of the patients had had previous treatment of the
      dislocation. Preliminary traction was used for five patients (six hips), and open
      reduction and femoral shortening was performed in all hips. The functional result
      was assessed, according to the Iowa hip-rating system, after an average duration
      of follow-up of ten years and six months (range, six years and two months to
      sixteen years and ten months). Sixteen hips had an excellent result; seven, a
      good result; and two, a fair result. The average limb-length discrepancy was 0.8
      centimeter (range, zero to four centimeters), and the average foot-progression
      angle was 11 degrees (range, 0 to 30 degrees) of external rotation. According to
      Severin's classification of the radiographic appearance, seven hips had an
      excellent result; eleven, a good result; four, a fair result; and three, a poor
      result. Four of eleven hips that had evidence of osteonecrosis of the proximal
      part of the femur had a severe deformity, and one patient had radiographic
      evidence of moderate degenerative osteoarthrosis when she was sixteen years old.
      On the basis of this review, we suggest that a one-stage operative procedure
      consisting of open reduction, femoral shortening, and pelvic osteotomy (if
      necessary) for previously untreated congenital dislocation of the hip in children
      who are three to ten years old can result in remodeling of the acetabulum and a
      functional hip.

PMID- 9531202
TI  - Postoperative weight-bearing after a fracture of the femoral neck or an
      intertrochanteric fracture.
AB  - Sixty patients who had had operative treatment of a fracture of the femoral neck
      or an intertrochanteric fracture were allowed to bear weight as tolerated on the
      injured limb. The average age was seventy-seven years. Computerized gait-testing
      was performed at one, two, three, six, and twelve weeks postoperatively to
      quantify weight-bearing. For the purpose of analysis, the patients were divided
      into three groups according to whether they had internal fixation of a stable
      fracture, internal fixation of an unstable fracture, or a primary
      hemiarthroplasty. Thirty-two patients completed the entire twelve-week study. The
      average amount of weight that these patients placed on the injured limb increased
      progressively with time. The average load supported by the injured limb was 51
      per cent that of the uninjured limb at one week, and it gradually increased to 87
      per cent at twelve weeks. During the first three weeks, the patients who had had
      internal fixation bore substantially less weight than those who had had a
      hemiarthroplasty. By six weeks, we could detect no significant differences, with
      the numbers available, among the groups with regard to weight-bearing or other
      measured gait parameters. We concluded that elderly patients who are allowed to
      bear weight as tolerated after operative treatment of a fracture of the femoral
      neck or an intertrochanteric fracture appear to voluntarily limit loading of the
      injured limb.

PMID- 9531203
TI  - Effect of acute inpatient rehabilitation on outcome after fracture of the femoral
      neck or intertrochanteric fracture.
AB  - A study was performed to assess the impact of intensive inpatient rehabilitation
      on the outcome after a fracture of the femoral neck or an intertrochanteric
      fracture. Before 1990, our hospital did not have an inpatient rehabilitation
      program. On January 1, 1990, a diagnosis-related-group-exempt (DRG-exempt) acute
      rehabilitation program was initiated. Patients were discharged to this program
      after evaluation by a staff physiatrist. Before 1990, twenty-seven (9.0 per cent)
      of 301 patients were discharged to an outside rehabilitation facility. After
      January 1990, the percentage of patients who were discharged to the DRG-exempt
      program increased yearly, from nineteen (17 per cent) of 113 patients in 1990 to
      forty-one (64 per cent) of sixty-four patients in 1993; this difference was
      significant (p < 0.01). Before 1990, the average duration of the stay in the
      hospital was 21.9 days. After January 1990, the average duration for the patients
      who did not enter the rehabilitation program was 20.0 days whereas the average
      duration for those who did was 31.4 days (16.1 days for acute care and 15.6 days
      for the rehabilitation program). There were no differences in the hospital
      discharge status or in the walking ability, place of residence, need for home
      assistance, or independence in basic and instrumental activities of daily living
      at the six and twelve-month follow-up examinations between patients who had been
      managed before initiation of the rehabilitation program and those managed after
      it or between patients who had been discharged to this program after its
      initiation and those who had not. These results raise serious questions regarding
      the global cost-effectiveness of these programs for patients who have had a
      fracture of the femoral neck or an intertrochanteric fracture.

PMID- 9531204
TI  - Elevated peak plantar pressures in patients who have Charcot arthropathy.
AB  - Although diabetes and peripheral neuropathy are perhaps the most important risk
      factors for neuropathic osteoarthropathy, we hypothesized that peak plantar
      pressures may also be higher in patients who have this condition. We are unaware
      of any reports in the medical literature that have specifically addressed this
      hypothesis. We obtained data from the medical records of 164 diabetic patients
      who had been managed in a multidisciplinary tertiary-care diabetic foot-specialty
      clinic. We then divided the patients into four groups: those who had acute
      Charcot arthropathy, those who had neuropathic ulceration, those who had
      neuropathy without ulceration, and those who had neither neuropathy nor
      ulceration. The peak plantar pressures were significantly higher in the patients
      who had acute Charcot arthropathy and those who had a neuropathic ulcer (p <
      0.001 for both) compared with the pressures in those who had no history of
      arthropathy and those who had neuropathy without ulceration. With the numbers
      available, we could not detect a significant difference in the peak pressure
      between the affected and the unaffected foot in the patients who had Charcot
      arthropathy (mean [and standard deviation], 100+/-8.5 compared with 101+/-9.6
      newtons per square centimeter; p > 0.05). However, the mean peak pressure was
      significantly higher on the ulcerated side than on the contralateral side in the
      patients who had a neuropathic ulcer (90+/-18.8 compared with 86+/-20.7 newtons
      per square centimeter; p < 0.02). Although the midfoot was the site of maximum
      involvement in all patients who had Charcot arthropathy, the peak plantar
      pressure was on the forefoot, suggesting that the forefoot may function as a
      lever, forcing collapse in the midfoot.

PMID- 9531205
TI  - Arthrodesis for the treatment of arthrosis of the ankle and osteonecrosis of the
      talus.
AB  - We evaluated the results of arthrodesis that had been performed for arthrosis of
      the ankle and osteonecrosis of the talus in nineteen patients. Twelve patients
      were men, and seven were women. The mean age of the patients was thirty-four
      years (range, nineteen to fifty-eight years). The median interval between the
      injury and the index operation was twenty-one months (range, six to 408 months).
      The arthrodesis was performed at the level of the ankle only in three patients
      and in both the ankle and the subtalar joint in sixteen. External fixation was
      used in thirteen patients, internal fixation was used in four, and no fixation
      was used in two. Supplemental bone graft from the iliac crest was used in
      fourteen patients, and local bone graft was used in five. The mean duration of
      follow-up was six years (range, two to fifteen years). The clinical result was
      excellent in seven patients, good in six, fair in three, and poor in three. Union
      was achieved in sixteen ankles, but it was delayed in one of them. Complications
      occurred in four patients: one had a tibial stress fracture, one had an infection
      at the site of a non-union, and two had malalignment in plantar flexion. Overall,
      the arthrodesis was successful in these patients. The use of rigid fixation and
      bone-grafting had a rate of success approximating that reported for primary
      arthrodesis in patients who do not have avascular necrosis.

PMID- 9531206
TI  - Arthrodesis with a short Huckstep nail as a salvage procedure for failed total
      knee arthroplasty.
AB  - Arthrodesis of the knee with use of a short Huckstep nail was performed in thirty
      three patients (thirty-three knees) after failure of a non-constrained total knee
      arthroplasty. The indication for the arthrodesis was an infection in thirty-one
      knees and a Charcot joint in two. Three knees had had a failed attempt at
      arthrodesis with use of external fixation. The Huckstep nail was inserted through
      the knee, retrograde into the femur, and then antegrade into the tibia. The
      duration of the operation averaged 104 minutes (range, sixty-five to 155
      minutes). Local bone graft was used in all knees. At the time of follow-up, at an
      average of forty-seven months (range, eighteen to ninety-four months), thirty
      knees (91 per cent) had radiographic evidence of union. The average time to union
      was 5.2 months (range, two to ten months) after the arthrodesis. Eight knees that
      had a grossly purulent infection were treated with debridement, which was
      followed by the arthrodesis as a second-stage procedure; the other knees had a
      one-stage arthrodesis. Only one of the thirty-one knees that had had an infection
      before the arthrodesis had a recurrence after it. Arthrodesis with a short
      Huckstep nail provides immediate axial and rotational stability and allows weight
      bearing without use of external support as well as placement of the knee in a
      slightly flexed and valgus position. In addition, the nail does not migrate and
      it may be used even when there is a standard-size prosthesis in the ipsilateral
      hip.

PMID- 9531207
TI  - Emboli observed with use of transesophageal echocardiography immediately after
      tourniquet release during total knee arthroplasty with cement.
AB  - The right atrium and the right ventricle of fifty-five patients were imaged with
      transesophageal echocardiography during fifty-nine total knee arthroplasties
      performed with cement and the use of general anesthesia. The patients ranged in
      age from thirty-two to eighty-three years (mean, 65.5 years). Cardiopulmonary
      parameters were measured with use of hemodynamic monitoring systems, such as
      pulse oximeters, pulmonary artery catheters, and radial artery catheters. In
      addition, a femoral vein catheter was inserted on the side of the operation in
      ten of the fifty-five patients. Showers of echogenic material traversing the
      right atrium, the right ventricle, and the pulmonary artery after the tourniquet
      was deflated were observed to various degrees in all patients and lasted three to
      fifteen minutes. The mean peak intensity occurred within thirty seconds (range,
      twenty-four to forty-five seconds) after the tourniquet was released. The mean
      mixed venous oxygen saturation (and standard error of the mean) decreased (from
      83+/-0.9 to 72+/-1.5 per cent) and the mean pulmonary arterial pressure increased
      (from 20+/-1.0 to 27+/-1.0 millimeters of mercury [2.67+/-0.13 to 3.60+/-0.13
      kilopascals]), compared with the values before the tourniquet was released, in
      all patients. The pulmonary vascular resistance index increased after release of
      the tourniquet (to a maximum of 328+/-29 dyne.s.cm(-5).m2; p = 0.00002) only in
      the patients who had echogenic material that was at least 0.5 centimeter in
      diameter. Clinical pulmonary embolism developed postoperatively in three
      patients; all three had had echogenic particles that were more than 0.5
      centimeter in maximum diameter on imaging. Blood aspirated from one of the
      pulmonary artery catheters and from five of the ten femoral vein catheters
      demonstrated fresh venous thrombus. Histological evaluation of the aspirates
      failed to demonstrate fat, marrow, or particles of polymethylmethacrylate.
      Surgeons should consider acute pulmonary embolism as a diagnosis when evaluating
      a patient who has hemodynamic collapse during total knee arthroplasty performed
      with cement.

PMID- 9531208
TI  - The results of treatment of synovitis of the wrist induced by particles of
      silicone debris.
AB  - Synovitis of the wrist induced by particles of silicone debris is a destructive
      inflammatory process. Many silicone-rubber carpal implants remain in place, and
      there are few reports regarding the treatment of this condition. The purpose of
      the present study was to examine the results of treatment of synovitis induced by
      particles of silicone debris. Twenty-eight patients were identified, with use of
      computerized indexing, as having been evaluated for silicone-induced synovitis
      between 1972 and 1992. Seventeen of the twenty-eight patients were included in
      the study. At the time of the latest follow-up, twelve of the seventeen patients
      had pain, thirteen of the fourteen patients for whom radiographs were available
      had evidence of osteolysis typical of that associated with debris-induced
      synovitis, and eight of the seventeen patients reported difficulty with
      activities of daily living because of problems with the wrist. Seven patients had
      been treated non-operatively, and ten had been treated operatively. With the
      small number of patients available for study, we could not detect a significant
      difference between the two groups with respect to pain, perceived limitation of
      motion, difficulty with activities of daily living, grip strength, or the total
      range of motion of the wrist. There was no significant difference between the two
      groups with regard to the age at the time of the initial procedure, the time to
      the diagnosis of the synovitis, and the duration of follow-up after treatment.
      There was no clear advantage to removal of the implant and debridement with or
      without arthrodesis of the wrist or other reconstructive procedures. We recommend
      caution when a reconstructive or salvage procedure in the wrist is selected for a
      patient who has synovitis induced by particles of silicone debris.

PMID- 9531209
TI  - Reconstruction of the distal aspect of the radius with use of an osteoarticular
      allograft after excision of a skeletal tumor.
AB  - Twenty-four patients had reconstruction of the distal aspect of the radius with
      use of an osteoarticular allograft, between 1974 and 1992, after excision of a
      giant-cell tumor (twenty patients), a desmoplastic fibroma (two patients), a
      chondrosarcoma (one patient), or an angiosarcoma (one patient). Nine giant-cell
      tumors were recurrent lesions, and eleven were extracompartmental primary lesions
      that had extended through the cortex or subchondral bone. The average age of the
      patients was 31.5 years (range, fifteen to sixty-one years); thirteen patients
      were female and eleven were male. Seventeen lesions involved the right wrist and
      seven involved the left wrist. The reconstruction was performed through a
      dorsoradial incision with use of a size-matched, preserved, fresh-frozen, distal
      radial allograft. All procedures included internal fixation and reconstruction of
      the radiocarpal ligaments. All patients were followed for a minimum of two years
      (average, 10.9 years; range, 2.1 to 22.3 years). At the time of follow-up, two
      patients -- one who had a giant-cell tumor and one who had a desmoplastic fibroma
      -- had a local recurrence. Eight patients needed a revision of the osteoarticular
      allograft, at an average of 8.1 years (range, 0.8 to 17.8 years) after the
      initial reconstruction. Seven of these patients had an arthrodesis and one had an
      amputation. The reason for the revision was a fracture of the allograft in four
      patients, recurrence of the tumor in one, pain in two, and volar dislocation of
      the carpus in one. There were fourteen other complications, including ulnocarpal
      impaction necessitating excision of the distal aspect of the ulna (four), painful
      hardware necessitating removal (four), rupture of the extensor pollicis longus
      tendon necessitating transfer of the extensor indicis proprius (two), fracture of
      the allograft necessitating open reduction and internal fixation (two), volar
      dislocation of the carpus necessitating closed reduction (one), and a ganglion of
      the dorsal aspect of the wrist necessitating excision (one). Of the sixteen
      patients in whom the osteoarticular allograft survived, three did not have pain,
      nine had pain in association with strenuous activities, and four had pain in
      association with moderate activities. Three patients reported no functional
      limitation, nine had limitation in the ability to perform strenuous activities,
      and four had limitation in the ability to perform moderate activities. The
      average range of motion of the wrist was 36 degrees of dorsiflexion, 21 degrees
      of volar flexion, 16 degrees of radial deviation, 15 degrees of ulnar deviation,
      58 degrees of supination, and 72 degrees of pronation. Reconstruction of the
      distal aspect of the radius with use of an osteoarticular allograft was
      associated with a low rate of recurrence of the tumor, a moderately high rate of
      revision, little pain in association with common activities, good function, and a
      moderate range of motion. Osteoarticular allografts are an option for
      reconstruction of the distal aspect of the radius after excision of a malignant
      tumor or a recurrent or locally invasive benign lesion.

PMID- 9531210
TI  - Failure of the polyethylene after bipolar hemiarthroplasty of the hip. A report
      of five cases.

PMID- 9531211
TI  - Progressive genu valgum secondary to a fibrous tether at the distal aspect of the
      femur. A case report.

PMID- 9531212
TI  - Non-union of the scapular body. A case report.

PMID- 9531213
TI  - Methods for locating missing patients for the purpose of long-term clinical
      studies.

PMID- 9531214
TI  - Disruption of the symphysis pubis during vaginal delivery. A case report.

PMID- 9531215
TI  - The role of access of joint fluid to bone in periarticular osteolysis. A report
      of four cases.

PMID- 9531216
TI  - Arthrodesis of the knee with a modular titanium intramedullary nail.

PMID- 9531217
TI  - Early excision of heterotopic ossification about the elbow followed by radiation
      therapy.

PMID- 9531218
TI  - Treatment of acute fractures with a collagen-calcium phosphate graft material. A
      randomized clinical trial.

PMID- 9531219
TI  - The effect of local infiltration with morphine before carpal tunnel release.

PMID- 9531220
TI  - Pregnancy in women with known HIV infection: what do we and don't we know?

PMID- 9531221
TI  - Early prevention vs late treatment for osteoporosis.

PMID- 9531222
TI  - Thrombolytic therapy for pulmonary embolism: is it effective? Is it safe? When is
      it indicated?

PMID- 9531223
TI  - Case of the month: Familial olivopontocerebellar atrophy. Autopsy Committee of
      the College of American Pathologists.

PMID- 9531224
TI  - Relation between the time to achieve the lower limit of the APTT therapeutic
      range and recurrent venous thromboembolism during heparin treatment for deep vein
      thrombosis.
AB  - BACKGROUND: Randomized trials have demonstrated the importance of achieving
      adequate heparinization early in the course of therapy. Recently, some authors
      reported a pooled analysis of selected studies in the literature that suggested
      that there is no convincing evidence that the risk of recurrent venous
      thromboembolism is critically dependent on achieving a therapeutic activated
      partial thromboplastin time result at 24 to 48 hours. METHODS: We provide the
      analyses of patient groups entered into our series of 3 consecutive double-blind
      randomized trials evaluating initial heparin therapy for proximal deep venous
      thrombosis. RESULTS: Logistic regression analysis of the patient groups receiving
      the less intense initial intravenous heparin dose of 30,000 U/24 h demonstrated
      that subtherapy for 24 hours predicted the onset of venous thromboembolic events.
      Failure to achieve a therapeutic activated partial thromboplastin time by 24
      hours was associated with a 23.3% frequency of venous thromboembolism vs 4% to 6%
      for those whose activated partial thromboplastin time exceeded the therapeutic
      threshold by 24 hours (P=.02). Time-to-event analysis shows the increased
      frequency of recurrent venous thromboembolic events during the period of study in
      patients who were subtherapeutic for 24 hours compared with those who were
      therapeutic (P=.001). CONCLUSIONS: Our findings reaffirm the clinical importance
      of rapidly achieving therapeutic levels of heparin. Patients who failed to
      achieve the therapeutic threshold by 24 hours were at an increased risk of
      subsequent recurrent venous thromboembolism. These findings are independently
      supported by the results of a randomized trial comparing different intensities of
      initial heparin treatment by continuous infusion.

PMID- 9531225
TI  - Treatment and outcomes of acute myocardial infarction among patients of
      cardiologists and generalist physicians.
AB  - BACKGROUND: Both cardiologists and generalist physicians care for patients with
      acute myocardial infarction, but little is known about their patients'
      characteristics, treatments, and outcomes. METHODS: We identified attending and
      consulting physicians, patient characteristics, drugs, procedures, and mortality
      from clinical and administrative records of 1620 Medicare beneficiaries aged 65
      to 79 years who were treated for acute myocardial infarction at 285 hospitals in
      Texas during 1990. RESULTS: Patients treated by attending cardiologists were
      younger, had prior congestive heart failure less frequently, and were initially
      treated in hospitals offering coronary angioplasty or bypass surgery more often
      than patients treated by attending generalist physicians (for each, P<.004).
      Adjusting for patient and hospital characteristics, cardiologists were more
      likely than generalist physicians to prescribe thrombolytic therapy and aspirin
      (P<.05) but not beta-adrenergic blocking agents (beta-blockers). Cardiologists
      used coronary angiography and angioplasty more often (P<.003), but not
      echocardiography or exercise testing. Adjusted 1-year mortality did not differ
      significantly between patients of attending cardiologists and generalist
      physicians (odds ratio, 1.01; 95% confidence interval, 0.76-1.35) or between
      patients of generalist physicians with and without a consulting cardiologist
      (odds ratio, 0.83; 95% confidence interval, 0.60-1.16). However, patients
      initially admitted to hospitals offering coronary angioplasty and bypass surgery
      had lower adjusted 1-year mortality than patients admitted to other hospitals
      (odds ratio, 0.68; 95% confidence interval, 0.47-0.98). CONCLUSIONS: Compared
      with generalist physicians, cardiologists used some, but not all, effective drugs
      more frequently, as well as coronary angiography and angioplasty. Although these
      differences were not associated with lower adjusted mortality among
      cardiologists' patients, cardiologists were more likely to treat patients in
      hospitals with better outcomes. Future studies should identify organizational
      factors that improve outcomes of myocardial infarction.

PMID- 9531226
TI  - Factors influencing the time to thrombolysis in acute myocardial infarction. Time
      to Thrombolysis Substudy of the National Registry of Myocardial Infarction-1.
AB  - BACKGROUND: The Time to Thrombolysis Substudy of the National Registry for
      Myocardial Infarction provided the opportunity to identify factors that delay
      thrombolytic treatment of patients with ST-segment elevation acute myocardial
      infarction. PARTICIPANTS: Forty-two participating registry hospitals volunteered
      for the Time to Thrombolysis Substudy. METHODS: A case report form was developed
      to collect time points for emergency department arrival (door), recording of the
      electrocardiogram (ECG) (data), entry of the order to give a thrombolytic drug
      (decision), and initiation of the thrombolytic infusion (drug) as defined by the
      National Heart Attack Alert Program. The impact of mode of transportation to the
      hospital, sex, policy-driven cardiology consultation and/or contact of the
      primary care physician on door-to-drug time, and each component interval were
      determined in 1755 patients who were treated with recombinant tissue-type
      plasminogen activator (A1-teplase). The t test was used for comparison of means
      and the nonparametric sign test was used for medians. RESULTS: A minority of
      patients arrived at the hospital by ambulance, although more women (49.6%)
      arrived by ambulance than men (40.9%). However, women arrived at hospitals
      significantly later after onset of symptoms than men. It took half as long for
      patients arriving by ambulance to be seen by the physician than those who
      transported themselves to the hospital. It took longer for women to have the
      initial 12-lead ECG recorded than men. The decision to order a thrombolytic agent
      was delayed by 22 minutes and median door-to-drug time by 21 minutes in those
      patients who had a cardiac consultation over those in whom the drug was ordered
      and infusion was initiated by the emergency physician. Although the initial 12
      lead ECG showed ST-segment elevation in 86% of patients who received the
      thrombolytic drugs, with no difference between men and women and no difference in
      the rate of cardiology consultation between men and women (77%), door-to-decision
      time and door-to-drug time were substantially longer for women having
      consultation than men. There was no significant difference in door-to-decision
      time between men and women when no consultation was performed, but it still took
      longer for a drug infusion to be initiated in women. Contacting the primary care
      physician delayed the decision to give a thrombolytic drug by 18 minutes and the
      administration of the drug by 20 minutes, but there were no differences between
      men and women. Preparation of the drug in the pharmacy resulted in significant
      delay compared with mixing it in the emergency department. CONCLUSIONS: Hospital
      practices and policies, including contacting the primary care physician prior to
      the initiation of a lytic drug, cardiology consultation, and preparation of the
      drug in the pharmacy rather than in the emergency department, significantly delay
      the goal of early treatment of patients with ST segment elevation acute
      myocardial infarction. Delays in hospital arrival for women are compounded by
      delays in the decision to treat them with a thrombolytic drug and initiation of
      the drug therapy in those women who receive consultation compared with men. Other
      delays in acquiring the first ECG and initiating the drug infusion in women are
      not explained.

PMID- 9531227
TI  - Incidence and consequences of pregnancy in women with known duration of HIV
      infection. Italian Seroconversion Study Group.
AB  - BACKGROUND: The increasing incidence of human immunodeficiency virus (HIV)
      infection in women of childbearing age led us to evaluate whether pregnancy
      affects the natural history of this disease. OBJECTIVES: To conduct a prospective
      study of women with known dates of HIV seroconversion to describe the incidence
      and outcome of pregnancy and to assess differences according to age and exposure
      group. To compare the rate of disease progression between pregnant and
      nonpregnant women. PATIENTS: All participants, recruited from 14 clinical centers
      in Italy, had documented HIV-seronegative test results followed by confirmed
      positive test results within 2 years. RESULTS: A total of 331 women, who had
      seroconversion between 1981 and 1994, were followed up for a median of 5.5 years
      from seroconversion; 94 developed HIV-related diseases, 47 developed acquired
      immunodeficiency syndrome, and 53 had at least 1 CD4 cell count lower than 0.10 x
      10(9)/L (< 100 cells/mm3). Thirty-eight women (11.5%) were pregnant at the time
      of HIV seroconversion and 31 (9.4%) became pregnant after HIV seroconversion
      (cumulative incidence of pregnancy within 8 years of seroconversion, 28.9%; 95%
      confidence interval, 21.6%-36.2%). Forty-five (65.2%) of the 69 pregnancies were
      carried to term. There were no discernible differences in these findings by age
      or exposure group. Pregnant women did not experience a more rapid rate of
      progression of disease, even when adjusting for age, exposure group, CD4 cell
      count, or use of treatment (adjusted relative hazards: HIV-related diseases,
      0.72; acquired immunodeficiency syndrome, 0.69; CD4 cell count <0.10 x 10(9)/L,
      1.24). CONCLUSION: Women infected with HIV continue to become pregnant after
      seroconversion, yet pregnancy does not appear to influence the rate of
      progression of HIV disease.

PMID- 9531228
TI  - The clinical course of patients with suspected pulmonary embolism.
AB  - BACKGROUND: The outcome of patients with suspected pulmonary embolism is known to
      a limited extent only. OBJECTIVE: To address this limited knowledge in a cohort
      in whom pulmonary embolism was proved or ruled out. METHODS: Consecutive patients
      with clinically suspected pulmonary embolism underwent lung scintigraphy and
      angiography if required. Pulmonary embolism was excluded by normal results of a
      lung scan or angiogram, and, if so, anticoagulant therapy was withheld. Pulmonary
      embolism was proved with a high-probability perfusion-ventilation lung scan or a
      confirmatory angiogram if a nondiagnostic lung scan was obtained. These patients
      were treated with heparin intravenously and anticoagulants orally on a long-term
      basis. All patients were followed up for 6 months, with a special focus on
      recurrent thromboembolism, bleeding complications, and mortality. RESULTS: A
      total of 487 consecutive inpatients and outpatients were included. Pulmonary
      embolism was excluded or proved in 243 and 193 patients, respectively. In 51
      patients a definite diagnosis could not be established. The overall prevalence of
      pulmonary embolism was 39%. In patients in whom pulmonary embolism was proved,
      excluded, or uncertain, recurrent venous thromboembolism was observed in 2.6%,
      0.9%, and 2%, respectively. Serious bleeding complications occurred in 7 patients
      (3.3%; 95% confidence interval [CI], 1.8%-6.3%), 2 cases of which were fatal. The
      total mortality after 6 months in patients with proved or excluded pulmonary
      embolism was 17% (95% CI, 12%-23%) and 11% (95% CI, 7%-15%), respectively. Death
      was related to (recurrent) pulmonary embolism in 5% and 0% of these cases,
      respectively. CONCLUSIONS: During a 6-month period, recurrent pulmonary embolism
      occurred in approximately 5 patients (2.5%) who were treated for a previous
      episode. Fatal bleeding complications attributable to the use of anticoagulants
      were encountered in 1%. The mortality among patients with suspected pulmonary
      embolism was considerable. However, most deaths were unrelated to pulmonary
      embolism, but were the result of serious underlying illnesses.

PMID- 9531229
TI  - Progress toward the elimination of hepatitis B virus transmission among health
      care workers in the United States.
AB  - BACKGROUND: Hepatitis B virus (HBV) infection is a well-recognized occupational
      risk for health care workers (HCWs). Vaccination coverage, disease trends, and
      the need for booster doses after hepatitis B vaccination of adults have been the
      subject of intense study during the 15 years of the vaccine's availability.
      METHODS: Vaccination coverage of HCWs was determined from a review of medical
      records on a sample of employees from 113 randomly selected hospitals. The number
      of HBV infections among HCWs and the general US population for 1983 through 1995
      was estimated from national surveillance data. Studies on long-term protection
      after hepatitis B vaccination of adults were reviewed. RESULTS: A total of 2837
      employee medical records were reviewed; 2532 employees (90%) were eligible to
      receive hepatitis B vaccine, and 66.5% of them (95% confidence interval, 61.9%
      70.9%) had received 3 doses of hepatitis B vaccine. Vaccination coverage was
      highest (75%) for personnel with frequent exposure to infectious body fluids
      (phlebotomists, laboratory personnel, and nursing staff) and lowest (45%) for
      employees at low risk for exposure (dietary and clerical staff). The number of
      HBV infections among HCWs declined from 17,000 in 1983 to 400 in 1995. The 95%
      decline in incidence observed among HCWs is 1.5-fold greater than the reduction
      in incidence in the general US population. Studies on long-term protection
      demonstrate that vaccine-induced protection persists at least 11 years even when
      titers of antibody to hepatitis B surface antigen decline below detectable
      levels. CONCLUSIONS: Although a high percentage of HCWs have been fully
      vaccinated with hepatitis B vaccine, efforts need to be made to improve this
      coverage. There has been a dramatic decrease in the number of HBV infections
      among HCWs who are now at lower risk of HBV infection than the general US
      population. Vaccine-induced protection persists at least 11 years and booster
      doses are not needed at this time for adults who have responded to vaccination.

PMID- 9531230
TI  - Low-dose esterified estrogen therapy: effects on bone, plasma estradiol
      concentrations, endometrium, and lipid levels. Estratab/Osteoporosis Study Group.
AB  - BACKGROUND: Prospective studies have shown that doses equivalent to conjugated
      equine estrogens of 0.625 mg/d or higher are needed to produce a significant
      increase in bone mineral density of the lumbar spine. OBJECTIVES: To determine
      the effects of unopposed esterified estrogens on bone mineral density, lipid
      levels, and endometrial tissue structure, and to relate these effects to changes
      in plasma estradiol levels. METHODS: Four hundred six postmenopausal women were
      given calcium, 1000 mg/d, and randomly assigned to receive continuous esterified
      estrogens (0.3, 0.625, or 1.25 mg/d) or placebo for 24 months. Bone mineral
      density measurements and endometrial and laboratory assessments were conducted
      every 6 months; plasma estradiol concentrations were measured after 12, 18, and
      24 months. RESULTS: All doses of esterified estrogens produced significant
      increases in bone mineral density of the lumbar spine compared with baseline and
      with placebo at 6, 12, 18, and 24 months. Mean plasma estradiol levels increased
      with esterified estrogens dose, and individual subject bone mineral density
      changes appeared related to plasma estradiol concentrations. Clinically relevant
      rates of endometrial hyperplasia were noted only in the groups receiving 0.625
      and 1.25 mg of esterified estrogens daily. Lipid changes were dose related and
      apparent in all groups. CONCLUSIONS: Esterified estrogens at doses from 0.3 to
      1.25 mg/d, administered unopposed by progestin, produce a continuum of positive
      changes on bone and lipids. Plasma estradiol concentrations increased with
      esterified estrogens dose and were related to positive bone mineral densities.
      The 0.3-mg dose resulted in positive bone and lipid changes without inducing
      endometrial hyperplasia.

PMID- 9531231
TI  - Treatment with alendronate prevents fractures in women at highest risk: results
      from the Fracture Intervention Trial.
AB  - BACKGROUND: The efficacy of antiresorptive therapy in preventing fractures in
      women at highest fracture risk, such as very elderly women or those with severe
      osteoporosis, is uncertain. PARTICIPANTS AND METHODS: Using data from a double
      blind, randomized, placebo-controlled clinical trial that enrolled 2027
      postmenopausal women aged 55 to 81 years with low femoral neck bone mineral
      density (BMD) and existing vertebral fractures, we examined the consistency of
      the effect of treatment with alendronate sodium in preventing fractures within a
      priori-specified risk subgroups defined at baseline by age, bone density, number
      of preexisting vertebral fractures, and history of postmenopausal fracture. The
      women were randomized to oral administration of alendronate or placebo and
      followed up for an average of 2.9 years. The initial dose of alendronate sodium
      was 5 mg/d; the dosage was increased from 5 to 10 mg/d at 24 months. New
      vertebral fractures, the primary end point of this arm of the trial, were defined
      by morphometry as a decrease of 20% and at least 4 mm in any vertebral height
      between baseline and a follow-up radiograph at 36 months. Incident clinical
      fractures, the secondary end point, included nonspine and clinical (symptomatic)
      vertebral fractures. All clinical fractures were confirmed with x-ray film
      reports or, in the case of clinical vertebral fractures, x-ray films. RESULTS:
      Overall, there was a 47% significant reduction in risk of new vertebral fractures
      in the alendronate group compared with the placebo group. The reduction in risk
      of new vertebral fracture was consistent across fracture risk categories
      including age (relative risk [RR], 0.49 in women < 75 years compared with 0.62 in
      those > or = 75 years), BMD (RR, 0.54 in women with a femoral neck BMD < 0.59
      g/cm2 [median] compared with 0.53 in those with a BMD > or = 0.59 g/cm2), and
      number of preexisting vertebral fractures (RR, 0.58 in women with 1 vertebral
      fracture compared with 0.52 in those with > or = 2). The overall significant 28%
      reduction in risk of incident clinical fractures in the alendronate group
      compared with the placebo group was also observed within these subgroups.
      Compared with the number of lower-risk women, a similar or smaller number of high
      risk women needed to be treated to prevent 1 fracture. For example, 8 women aged
      75 years or older compared with 9 women younger than 75 years, or 4 women with 2
      or more existing vertebral fractures compared with 16 women with 1 existing
      vertebral fracture, needed to be treated with alendronate for 5 years to prevent
      1 new vertebral fracture. CONCLUSIONS: Alendronate effectively reduces fracture
      risk in postmenopausal women with vertebral fractures and low BMD, including
      those women at highest risk because of advanced age or severe osteoporosis. Since
      the risk reductions observed with alendronate treatment were consistent within
      fracture risk categories, more fractures were prevented by treating women at
      highest risk.

PMID- 9531232
TI  - Gastrointestinal tract bleeding associated with naproxen sodium vs ibuprofen.
AB  - BACKGROUND: The risk of gastrointestinal tract bleeding requiring hospitalization
      associated with naproxen sodium was compared with that with ibuprofen, using a
      prescription database to approximate over-the-counter dosing. OBJECTIVE: To
      evaluate the safety of naproxen sodium. METHODS: A claims database containing
      Ohio Medicaid data from January 1986 through February 1993 and Michigan Medicaid
      data from April 1983 through July 1993 was used to compare 101,318 patients
      dispensed naproxen sodium with 277,601 patients dispensed ibuprofen. Using a case
      cohort design, all 59 patients from the full cohort who had been hospitalized
      with upper gastrointestinal tract bleeding (UGIB) that developed within 14 days
      after the first prescription for the study drugs were compared with a subcohort
      made up of a 10% random sample of subjects selected from the combined drug
      cohorts. RESULTS: The incidence of UGIB occurring within 14 days after the first
      prescription in the naproxen sodium cohort was 26 (0.026%) of 101,318 (95%
      confidence interval [CI], 0.017%-0.038%), compared with 33 (0.012%) of 277,601
      patients (95% CI, 0.008%-0.017%) in the ibuprofen cohort. Overall, the use of
      naproxen sodium vs ibuprofen was associated with an adjusted relative risk of 2.0
      (95% CI, 1.1-3.8). Among people with multiple prescriptions, the crude relative
      risk for those receiving therapy in a dose typical of over-the-counter use was
      4.1 (95% CI, 1.2-13.8). CONCLUSIONS: The overall incidence of UGIB is low with
      both drugs. There is little additional absolute risk posed by the use of low-dose
      naproxen sodium, compared with low-dose ibuprofen, despite an increased relative
      risk. However, given the widespread use of these drugs, a substantial number of
      additional cases of UGIB could result from use of naproxen sodium. This increased
      risk should be considered, especially for patients whose baseline risk of UGIB is
      elevated.

PMID- 9531233
TI  - Erythema migrans-like rash illness at a camp in North Carolina: a new tick-borne
      disease?
AB  - BACKGROUND: Borrelia burgdorferi, the causative agent of Lyme disease, has never
      been isolated from a patient thought to have acquired Lyme disease in any
      southeastern state. OBJECTIVE: To investigate 14 cases of an erythema migrans
      (EM)-like rash illness that occurred during 2 summers at an outdoor camp in
      central North Carolina in an effort to determine the etiologic, epidemiological,
      and clinical aspects of this illness. METHODS: Using active surveillance, we
      identified cases of clinically diagnosed EM in residents and staff of the camp.
      We collected clinical and demographic information; history of exposure to ticks;
      acute and convalescent serum antibodies to B. burgdorferi, Rickettsia rickettsii,
      and Ehrlichia chaffeensis; and cultures for spirochetes from biopsy specimens of
      skin lesions. Serum samples from a group of residents and staff who did not
      develop rashes were tested for the same antibodies. We speciated ticks removed
      from people and collected from vegetation. RESULTS: We identified 14 cases of EM
      like rash illness during the 2 summers. Of the 14 case-patients, 10 had
      associated mild systemic symptoms and 1 had documented fever. All 14 case
      patients had removed attached ticks, and 8 remembered having removed a tick from
      the site where the rash developed a median of 12 days earlier (range, 2-21 days).
      One tick removed from the site where a rash later developed was identified as
      Amblyomma americanum, the Lone Star tick; 97% of ticks collected from vegetation
      and 95% of ticks removed from people were A. americanum. No spirochetes were
      isolated from skin biopsy specimens. Paired serum samples from 13 case-patients
      did not show diagnostic antibody responses to B. burgdorferi or other tick-borne
      pathogens. CONCLUSIONS: This investigation suggests the existence of a new tick
      associated rash illness. We suspect that the disease agent is carried by A.
      americanum ticks. In the southern United States, EM-like rash illness should no
      longer be considered definitive evidence of early Lyme disease.

PMID- 9531234
TI  - How sleep and mental disorders are related to complaints of daytime sleepiness.
AB  - BACKGROUND: Daytime sleepiness is widespread and has negative impacts on the
      public sector. OBJECTIVE: To ascertain the incidence and prevalence of daytime
      sleepiness and associated risk factors in the general population. METHOD: In
      1994, a representative sample of the non-institutionalized British population
      aged 15 years or older was interviewed via telephone using an expert computer
      assisted program designed to facilitate surveys of this type (Sleep-Eval, M. M.
      Ohayon, Montreal, Quebec). Subjects were classified into 3 groups based on the
      severity of their daytime sleepiness. We completed 4972 interviews (acceptance
      rate, 79.6%). RESULTS: Severe daytime sleepiness was reported in 5.5% (95%
      confidence interval, 4.9%-6.1%) of the sample, and moderate daytime sleepiness in
      another 15.2% (95% confidence interval, 14.2%-16.2%). Associated factors with
      severe daytime sleepiness included female sex, middle age, napping, insomnia
      symptoms, high daily caffeine consumption, breathing pauses or leg pain in sleep,
      depressive disorder (based on the Diagnostic and Statistical Manual of Mental
      Disorders, Fourth Edition, criteria), falling asleep while reading or watching
      television, and motor vehicle crashes or accidents involving use of machinery.
      Moderate daytime sleepiness was associated with female sex, napping, insomnia
      symptoms, arthritis or heart disease, and gross motor movements during sleep.
      CONCLUSIONS: It is likely that daytime sleepiness deleteriously affects work
      activities, social and/or marital life, and exhibits a negative socioeconomic
      impact. In addition, the risk of a motor vehicle crash appears to be higher in
      this specific population: twice as many subjects operating a motor vehicle or
      using machine tools reported having a crash or accident, respectively, in the
      previous year in the groups with severe daytime sleepiness or moderate daytime
      sleepiness than did the general population with no daytime sleepiness. The high
      prevalence rates of daytime sleepiness and multiplicity of related factors
      mandate further scrutiny by public health officials.

PMID- 9531235
TI  - Efficacy of a smoking cessation program for hospital patients.
AB  - BACKGROUND: Hospitalization may be an opportune time to change smoking behavior
      because it requires smokers to abstain from tobacco at the same time that illness
      can motivate them to quit. A hospital-based intervention may promote smoking
      cessation after discharge. METHODS: We tested the efficacy of a brief bedside
      smoking counseling program in a randomized controlled trial at Massachusetts
      General Hospital, Boston. The 650 adult smokers admitted to the medical and
      surgical services were randomly assigned to receive usual care or a hospital
      based smoking intervention consisting of (1) a 15-minute bedside counseling
      session, (2) written self-help material, (3) a chart prompt reminding physicians
      to advise smoking cessation, and (4) up to 3 weekly counseling telephone calls
      after discharge. Smoking status was assessed 1 and 6 months after hospital
      discharge by self-report and validated at 6 months by measurement of saliva
      cotinine levels. RESULTS: One month after discharge, more intervention than
      control patients were not smoking (28.9% vs 18.9%; P=.003). The effect persisted
      after multiple logistic regression analyses adjusted for baseline group
      differences, length of stay, postdischarge smoking treatment, and hospital
      readmission (adjusted odds ratio, 2.19; 95% confidence interval, 1.34-3.57). At 6
      months, the intervention and control groups did not differ in smoking cessation
      rate by self-report (17.3% vs 14.0%; P=.26) or biochemical validation (8.1% vs
      8.7%; P=.72), although the program appeared to be effective among the 167
      patients who had not previously tried to quit smoking (15.3% vs 3.7%; P=.01).
      CONCLUSIONS: A low-intensity, hospital-based smoking cessation program increased
      smoking cessation rates for 1 month after discharge but did not lead to long-term
      tobacco abstinence. A longer period of telephone contact after discharge might
      build on this initial success to produce permanent smoking cessation among
      hospitalized smokers.

PMID- 9531237
TI  - Diagnosis of chronic fatigue syndrome.

PMID- 9531236
TI  - Free-floating thrombus and pulmonary embolism.

PMID- 9531238
TI  - Sources of end-of-life ethics publications.

PMID- 9531239
TI  - Warfarin therapy in the nursing home.

PMID- 9531240
TI  - Prolonged QT interval and ventricular fibrillation after treatment with
      sublingual nifedipine for malignant hypertension.

PMID- 9531241
TI  - Salt, blood pressure, and cointervention.

PMID- 9531242
TI  - Myocardial ischemia in a patient with chronic refractory idiopathic
      thrombocytopenic purpura.

PMID- 9531243
TI  - Does insulin use increase bone mineral density in patients with non-insulin
      dependent diabetes mellitus?

PMID- 9531244
TI  - Orbital hemorrhage after thrombolytic therapy.

PMID- 9531245
TI  - Systemic lupus erythematosus: a risk factor for pneumonia caused by Legionella
      micdadei?

PMID- 9531246
TI  - A piece of my mind. Aging and caring.

PMID- 9531247
TI  - Triglyceride: the forgotten risk factor.

PMID- 9531248
TI  - Triglyceride concentration and ischemic heart disease: an eight-year follow-up in
      the Copenhagen Male Study.
AB  - BACKGROUND: The role of triglycerides as a risk factor of ischemic heart disease
      (IHD) remains controversial. For the present study, we examined the relation
      between fasting triglycerides and risk of IHD in the Copenhagen Male Study.
      METHODS AND RESULTS: Baseline measurements of fasting lipids and other IHD risk
      factors were obtained for 2906 white men (age range, 53 to 74 years) who were
      initially free of overt cardiovascular disease. During an 8-year follow-up
      period, 229 men had a first IHD event. Crude cumulative incidence rates of IHD
      were 4.6% for the lowest, 7.7% for the middle, and 11.5% for the highest third of
      triglyceride levels (P for trend <.001). Compared with the lowest third level and
      adjusted for age, body mass index, alcohol, smoking, physical activity,
      hypertension, non-insulin-dependent diabetes mellitus, social class, and LDL and
      HDL cholesterol, relative risks of IHD (95% confidence interval) were 1.5 (1.0 to
      2.3; P=.05) and 2.2 (1.4 to 3.4; P<.001) for the middle and highest third of
      triglyceride levels, respectively. When triglyceride levels were stratified by
      HDL cholesterol levels (triglyceride third multiplied by HDL cholesterol third),
      a clear gradient of risk of IHD was found with increasing triglyceride levels
      within each level of HDL cholesterol, including high HDL cholesterol level, which
      are thought to provide protection against IHD. CONCLUSIONS: In middle-aged and
      elderly white men, a high level of fasting triglycerides is a strong risk factor
      of IHD independent of other major risk factors, including HDL cholesterol.

PMID- 9531249
TI  - Interaction of coagulation defects and cardiovascular risk factors: increased
      risk of myocardial infarction associated with factor V Leiden or prothrombin
      20210A.
AB  - BACKGROUND: A genetic variation located in the 3'-untranslated region of the
      prothrombin gene (prothrombin 20210 G-->A) was recently described as a risk
      factor for venous thrombosis. We examined how the presence of this mutation
      affected the risk of myocardial infarction in a population-based case-control
      study. Furthermore, we studied the risk of myocardial infarction associated with
      the simultaneous presence of a coagulation defect (ie, the 20210 AG genotype of
      prothrombin or the factor V Leiden mutation) and Major cardiovascular risk
      factors. METHODS AND RESULTS: Among 560 men with a first myocardial infarction
      before the age of 70 years, 1.8% were heterozygous carriers of the 20210 variant
      of the prothrombin gene. The control group consisted of 646 men who were
      frequency matched by age. In the latter group, the frequency of the 20210 AG
      genotype was 1.2%. The risk of myocardial infarction in the presence of the AG
      genotype was increased by 50% (odds ratio, 1.5; 95% confidence interval [95% CI],
      0.6 to 3.8). The risk of myocardial infarction for carriership of factor V Leiden
      mutation was increased by 40% (odds ratio, 1.4; 95% CI, 0.8 to 2.2). When a
      coagulation defect was present (ie, the 20210 AG prothrombin genotype or the
      factor V Leiden mutation), the risk of myocardial infarction for carriers versus
      noncarriers was 1.4 (95% CI, 0.9 to 2.2). This risk was substantially increased
      when one of the major cardiovascular risk factors of smoking, hypertension,
      diabetes mellitus, or obesity also was present, with odds ratios varying between
      3 and 6. These risks exceeded those of the single effects of the cardiovascular
      risk factors (ie, in the absence of the coagulation defect). CONCLUSIONS: We
      conclude that in men the 20210 G-->A variant of prothrombin is associated with an
      increased risk of myocardial infarction. The combined presence of major
      cardiovascular risk factors and carriership of a coagulation defect increases the
      risk considerably.

PMID- 9531250
TI  - Prospective temporal analysis of the onset of preinfarction angina versus
      outcome: an ancillary study in TIMI-9B.
AB  - BACKGROUND: The timing of onset of angina before myocardial infarction in
      relation to outcome is unknown. METHODS AND RESULTS: We prospectively determined
      the importance of the time of onset of preinfarction angina in relation to 30-day
      outcomes in the TIMI-9B study from standardized forms. Of the 3002 patients
      entered into the study, 425 reported angina before their myocardial infarction.
      Patients with angina onset within 24 hours of infarction had a lower 30-day
      cardiac event rate (mortality, recurrent myocardial infarction, heart failure, or
      shock) at 4% than those with onset of angina >24 hours (17%; P=.030). A history
      of any angina alone was not associated with reduced event rate. Peak creatine
      kinase levels tended to be lower in the group with angina within 24 hours. These
      benefits were not due to higher rates of use of antianginal medicines or aspirin
      and were not a consequence of differences in baseline characteristics or disease
      states (hypertension, hypercholesterolemia) among subgroups. CONCLUSIONS: These
      temporal observations are consistent with the concept of preconditioning by
      preinfarction angina but do not rule out other mechanisms.

PMID- 9531252
TI  - Quantitative evaluation of global and regional left ventricular diastolic
      function with color kinesis.
AB  - BACKGROUND: Diastolic wall motion asynchrony is a major determinant of impaired
      left ventricular (LV) filling in patients with concentric hypertrophy and
      coronary artery disease. We evaluated the ability of Color Kinesis, a new
      echocardiographic technique that color-encodes endocardial motion, to
      quantitatively assess global and regional LV filling properties. METHODS AND
      RESULTS: Color Kinesis images and mitral and pulmonary vein flow Doppler data
      were acquired in 29 patients with LV hypertrophy and 29 age-matched control
      subjects. In addition, Color Kinesis data were correlated to coronary
      angiographic findings in 15 patients with suspected coronary artery disease.
      Segmental analysis of Color Kinesis images was used to obtain time histograms of
      regional diastolic fractional area change, wherein early and late peaks (peaks 1
      and 2) reflected rapid LV filling and atrial contraction, respectively. Regional
      mean LV filling time and filling curves were used to objectively identify
      diastolic endocardial motion asynchrony in patients with LV hypertrophy and
      coronary artery disease. None of the mitral and pulmonary vein Doppler indices
      differentiated patients with normalized mitral Doppler profile (n=13) from
      control subjects, whereas reduced peak1/peak2 ratio and prolonged mean filling
      time indicated augmented contribution of atrial contraction toward LV filling
      (P<.05). In 22 of 25 patients with LV hypertrophy and preserved systolic function
      and in all patients with coronary artery disease, delayed diastolic endocardial
      motion was observed in at least one segment. CONCLUSIONS: Analysis of Color
      Kinesis images provides objective assessment of global and regional LV filling
      properties and allows identification of both diastolic dysfunction in patients
      with normalized Doppler indices and wall motion asynchrony.

PMID- 9531253
TI  - Evidence for cAMP-independent mechanisms mediating the effects of adrenomedullin,
      a new inotropic peptide.
AB  - BACKGROUND: Adrenomedullin (ADM), a new vasorelaxing and natriuretic peptide, may
      function as an endogenous regulator of cardiac function, because ADM and its
      binding sites have been found in the heart. We characterize herein the cardiac
      effects of ADM as well as the underlying signaling pathways in vitro. METHODS AND
      RESULTS: In isolated perfused, paced rat heart preparation, infusion of ADM at
      concentrations of 0.1 to 1 nmol/L for 30 minutes induced a dose-dependent,
      gradual increase in developed tension, whereas proadrenomedullin N-20 (PAMP; 10
      to 100 nmol/L), a peptide derived from the same gene as ADM, had no effect. The
      ADM-induced positive inotropic effect was not altered by a calcitonin gene
      related peptide (CGRP) receptor antagonist, CGRP8-37, or H-89, a cAMP-dependent
      protein kinase inhibitor. ADM also failed to stimulate ventricular cAMP content
      of the perfused hearts. Ryanodine (3 nmol/L), a sarcoplasmic reticulum Ca2+
      release channel opener, suppressed the overall ADM-induced positive inotropic
      effect. Pretreatment with thapsigargin (30 nmol/L), which inhibits sarcoplasmic
      reticulum Ca2+ ATPase and depletes intracellular Ca2+ stores, attenuated the
      early increase in developed tension produced by ADM. In addition, inhibition of
      protein kinase C by staurosporine (10 nmol/L) and blockade of L-type Ca2+
      channels by diltiazem (1 micromol/L) significantly decreased the sustained phase
      of ADM-induced increase in developed tension. Superfusion of atrial myocytes with
      ADM (1 nmol/L) in isolated left atrial preparations resulted in a marked
      prolongation of action potential duration between 10 and -50 mV transmembrane
      voltage, consistent with an increase in L-type Ca2+ channel current during the
      plateau. CONCLUSIONS: Our results show that ADM enhances cardiac contractility
      via cAMP-independent mechanisms including Ca2+ release from intracellular
      ryanodine- and thapsigargin-sensitive Ca2+ stores, activation of protein kinase
      C, and Ca2+ influx through L-type Ca2+ channels.

PMID- 9531251
TI  - Comparison of antiplatelet effects of aspirin, ticlopidine, or their combination
      after stent implantation.
AB  - BACKGROUND: This study was performed to analyze the influence of either aspirin,
      ticlopidine, or their combination on platelet activation and aggregation
      parameters after stent implantation. METHODS AND RESULTS: Sixty-one patients with
      successful implantation of a single Palmaz-Schatz stent in a native coronary
      artery were randomly assigned to either group A (aspirin 300 mg/d+ticlopidine
      2X250 mg/d), group B (ticlopidine 2X250 mg/d), or group C (aspirin 300 mg/d).
      Platelet activation was evaluated on days 1, 7, and 14 by flow cytometry
      measurement of expression of CD62p (p-selectin) and the binding of fibrinogen to
      the platelet surface glycoprotein IIb/IIIa receptor. Platelet aggregation was
      induced by addition of ADP or collagen. Differences between treatment groups were
      compared by ANOVA. Between days 1 and 14, we observed a significant decrease in
      collagen-induced platelet aggregation in group A (62.2+/-2.5% versus 36.9+/
      3.1%), whereas an increase was seen in group B (58.3+/-2.5% versus 67.7+/-3.2%)
      and no change was seen in group C (P<.0001). The ADP-induced aggregation declined
      significantly in group A (74.7+/-1.4% versus 55.3+/-2.6%), whereas a delayed
      reduction was seen in group B (72.0+/-3.0% versus 52.6+/-4.2%) and no change was
      seen in group C (P=.0017). The CD62p expression declined significantly in groups
      A (68.2+/-2.7% versus 41.3+/-2.7%) and B (64.8+/-2.9% versus 39.3+/-3.5%) but not
      in group C (P<.0001). Moreover, the fibrinogen binding decreased significantly in
      group A (61.0+/-4.3% versus 36.3+/-4.2%) and with delay in group B (58.3+/-2.2%
      versus 39.4+/-3.0%), whereas no alterations were seen in group C (P=.012).
      CONCLUSIONS: Our results demonstrate synergistic and accelerated platelet
      inhibitory effects of ticlopidine plus aspirin in patients after stent
      implantation compared with a monotherapy with either ticlopidine or aspirin
      alone.

PMID- 9531254
TI  - Induction of rat aortic smooth muscle cell growth by the lipid peroxidation
      product 4-hydroxy-2-nonenal.
AB  - BACKGROUND: Atherosclerotic lesion formation is a complex process, in part
      mediated by inflammatory and oxidative mechanisms including lipid peroxidation.
      To further characterize the potential role of lipid peroxidation products in
      atherogenesis, we studied the effects of 4-hydroxy-2-nonenal (HNE) on rat aortic
      smooth muscle cell growth. METHODS AND RESULTS: HNE, at concentrations of 1.0 and
      2.5 micromol/L, significantly stimulated rat aortic smooth muscle cell growth as
      determined by cell counts, [3H]-thymidine uptake, and incorporation of bromo
      deoxyuridine. To characterize the mechanism of HNE-induced mitogenesis, its
      effect on activation of intracellular growth signaling pathways was examined.
      Treatment with HNE resulted in activation of extracellular signal-regulated
      protein kinases ERK1 and ERK2, induction of c-fos and c-jun protein expression,
      and an increase in transcription factor AP-1 DNA binding activity. In addition,
      HNE induced expression of platelet-derived growth factor-AA (PDGF-AA) protein,
      and an anti-PDGF-AA antibody specifically inhibited HNE-mediated DNA synthesis,
      suggesting that growth factor induction may play a role in HNE-induced vascular
      smooth muscle cell growth. The role of redox-sensitive mechanisms in this process
      was further supported by the observation that HNE-induced DNA synthesis and AP-1
      activation were inhibited by the antioxidants N-acetylcysteine and pyrrolidine
      dithiocarbamate. CONCLUSIONS: These data demonstrate that HNE, one of several
      important lipid peroxidation products, induces rat aortic smooth muscle cell
      growth through redox-sensitive mechanisms and growth factor expression. These
      observations are consistent with a role for lipid peroxidation products in
      vascular smooth muscle cell growth in atherogenesis.

PMID- 9531255
TI  - Expression of LDL receptor, VLDL receptor, LDL receptor-related protein, and
      scavenger receptor in rabbit atherosclerotic lesions: marked induction of
      scavenger receptor and VLDL receptor expression during lesion development.
AB  - BACKGROUND: Atherosclerotic lesions contain foam cells that arise from monocyte
      macrophages and smooth muscle cells (SMCs) by excessive uptake of lipoproteins.
      There are many candidate receptors for the lipid accumulation, such as LDL
      receptor (LDLR), VLDL receptor (VLDLR), LDL receptor-related protein (LRP), and
      scavenger receptors (SRs). However, little quantitative information exists on the
      expression of these receptors in normal and atherosclerotic arteries. METHODS AND
      RESULTS: Competitive reverse transcription-polymerase chain reaction and in situ
      hybridization were used for the studies in New Zealand White (NZW) and Watanabe
      heritable hyperlipidemic (WHHL) rabbit aortic intima-medias. NZW rabbits were fed
      a 1% cholesterol diet for 0 (control group), 3, 6, or 14 weeks. LDLR mRNA
      expression was low in aortic intima-medias of all groups. Of the analyzed
      receptors, LRP had the highest expression in the control group, and its mRNA was
      induced threefold in the 14-week group, the aortas of which had extensive
      lesions. SR expression was low and VLDLR expression moderate in the control
      group. Both receptors were highly induced during cholesterol feeding (SRs, 3-fold
      and 270-fold induction; VLDLR, 15-fold and 100-fold induction in the 3-week and
      14-week groups, respectively). Comparable results were obtained from WHHL
      rabbits: high basal LRP mRNA in normal intima-medias; moderate induction of LRP
      and marked induction of SRs and VLDLR in fatty streaks and fatty plaques. In situ
      hybridization indicated that LRP and VLDLR were expressed in SMCs and
      macrophages. VLDLR expression was also observed in endothelial cells. SR
      expression was detected only in macrophages. CONCLUSIONS: SR and VLDLR mRNAs were
      highly induced in atherosclerotic lesions. VLDLR and LRP may be involved in the
      formation of both SMC-and macrophage-derived foam cells, whereas SRs play an
      important role in lipid uptake in macrophages.

PMID- 9531256
TI  - Serum cholesterol distribution and coronary heart disease risk: observations and
      predictions among middle-aged population in eastern Finland.
AB  - BACKGROUND: The purpose of the present study was to assess the implications of
      cholesterol distribution and its change on coronary heart disease (CHD) mortality
      and disease prevention at a population level. METHODS AND RESULTS: In five
      independent risk factor surveys (1972, 1977, 1982, 1987, and 1992) in eastern
      Finland, serum cholesterol was measured in 27721 randomly selected men and women
      aged 30 to 59 years. The association between cholesterol level and CHD risk and
      the prediction of the effect of different prevention strategies was estimated by
      use of logistic regression models. The entire cholesterol distribution of the
      population shifted markedly toward lower levels between 1972 and 1992. The
      proportion of subjects with a very high cholesterol level (> or =8.0 mmol/L),
      also decreased markedly, from 16% to 3%. The risk of CHD death among subjects
      with cholesterol > or =8.0 mmol/L was approximately 5-fold that of those
      individuals having cholesterol <5.0 mmol/L. Nevertheless, because CHD risk
      increases continuously as serum cholesterol increases, and because the number of
      people having only slightly or moderately increased serum cholesterol was large,
      most CHD deaths occurred among them. A 10% reduction in cholesterol levels in the
      entire population would subsequently reduce CHD mortality by 20%, as much as an
      effective treatment as a 25% decrease in serum cholesterol among all subjects
      with cholesterol >6.5 mmol/L and four times more than similar treatment of all
      subjects with cholesterol > or =8.0 mmol/L. CONCLUSIONS: The community-based
      population strategy in cardiovascular disease prevention was effective in
      decreasing cholesterol levels among the entire population, including the subjects
      with the highest cholesterol values. The balanced application of both high-risk
      and population strategies is needed for the effective prevention of CHD.

PMID- 9531257
TI  - Increasing burden of cardiovascular disease: current knowledge and future
      directions for research on risk factors.

PMID- 9531258
TI  - Images in cardiovascular medicine: infantile Marfan's syndrome.

PMID- 9531259
TI  - Images in cardiovascular medicine: amiodarone skin toxicity.

PMID- 9531260
TI  - Physical interaction between dendritic cells and tumor cells results in an
      immunogen that induces protective and therapeutic tumor rejection.
AB  - Dendritic cells (DCs) are potent professional APCs capable of presenting Ag in
      the context of costimulatory signals necessary for T cell activation. Although
      tumor cells express target Ags, they are generally incapable of stimulating an
      immune response. We show that the short term physical interaction of DCs and
      tumor cells, with or without cell fusion, results in rapid, efficient, and stable
      DC-tumor cell association. Immunization of naive mice with unselected, irradiated
      DC-tumor cell conjugates induces tumor-specific CD8+ cytotoxic T cells and
      protection from lethal tumor challenge. Furthermore, the immunogenicity of this
      cellular vaccine is dependent on the physical interaction of DCs and tumor cells
      before injection. Immunization with DCs and tumor cells after physical
      interaction can result in the regression of established tumors and persistent
      antitumor immunity. These results suggest that immunization with DC-tumor cell
      vaccines may be a simple, rapid, and potent strategy for tumor immunotherapy.

PMID- 9531261
TI  - Multiple mechanisms of peripheral T cell tolerance to the fetal "allograft".
AB  - The fetus represents a foreign entity to the maternal immune system, yet this
      "natural" allograft is not normally rejected. This unique situation provides a
      physiologic system to evaluate peripheral tolerance in which the maternal immune
      system is challenged with relatively rare Ags not previously encountered in the
      thymus. Using H-Y-specific TCR transgenic mice, we demonstrate that T cells
      specific for fetal Ags decrease in an Ag-specific manner during pregnancy and
      remain low postpartum, the result of an encounter with fetal cells expressing the
      appropriate MHC/peptide complexes. The finding that placental trophoblasts can
      induce Fas-mediated death of T cells is consistent with peripheral clonal
      deletion as one mechanism of tolerance. The remaining clonotypic T cells are
      unresponsive to antigenic stimulation, although neither TCR nor coreceptor is
      down-regulated. Our study demonstrates that specific recognition of fetal
      allogeneic Ags by maternal T cells results in tolerance induction of reactive T
      cells via multiple mechanisms.

PMID- 9531262
TI  - Dichotomous effects of beta-chemokines on HIV replication in monocytes and
      monocyte-derived macrophages.
AB  - The role of beta-chemokines in the pathogenesis of HIV disease remains undefined.
      Given the potent capacities of these proteins to attract mononuclear cells to
      inflammatory sites, such as lymph nodes of patients with HIV disease, the effects
      of exposure of monocytes and monocyte-derived macrophages to beta-chemokines
      before HIV infection were compared with their effects when added either
      simultaneously with or after HIV infection. In this system, HIV replication was
      substantially increased in cells that had been exposed to beta-chemokines before
      HIV infection. These effects were pertussis toxin sensitive. By contrast, HIV
      replication was inhibited in cells that had been exposed to beta-chemokines
      either simultaneously with or after HIV infection. These effects were not
      pertussis toxin sensitive. In view of this potent capacity of beta-chemokines to
      stimulate HIV replication, treatment approaches for HIV disease based on the
      apparent inhibitory activity of these proteins on viral replication should be
      undertaken with caution.

PMID- 9531263
TI  - Human myelomonocytic cells express an inhibitory receptor for classical and
      nonclassical MHC class I molecules.
AB  - Leukocyte activation can be negatively regulated by inhibitory receptors specific
      for MHC class I molecules. While one inhibitory receptor, Ig-like transcript 2
      (ILT2), is expressed by all lymphoid and myelomonocytic cell types, other
      receptors display a more selective tissue distribution. Here we characterize an
      inhibitory receptor, termed ILT4, which is selectively expressed in monocytes,
      macrophages, and dendritic cells (DCs), binds classical class I molecules and the
      nonclassical class I molecules HLA-G, and transduces negative signals that can
      inhibit early signaling events triggered by stimulatory receptors. ILT4 may
      control inflammatory responses and cytotoxicity mediated by myelomonocytic cells
      and may modulate their Ag-presenting functions, focusing immune responses to
      microbial challenges and avoiding autoreactivity.

PMID- 9531264
TI  - Distinct peptide loading pathways for MHC class II molecules associated with
      alternative Ii chain isoforms.
AB  - Mutant mouse strains expressing either p31 or p41 Ii chain appear equally
      competent with respect to their class II functional activities including Ag
      presentation and CD4+ T cell development. To further explore possibly divergent
      roles provided by alternative Ii chain isoforms, we compare class II structure
      and function in double mutants also carrying a null allele at the H2-DM locus. As
      for DM mutants expressing wild-type Ii chain, Aalpha(b)Abeta(b) dimers present in
      DM-deficient mice expressing either Ii chain isoform appear equally occupied by
      class II-associated Ii chain-derived peptides (CLIP). Surprisingly, in functional
      assays, these novel mouse strains exhibit strikingly different phenotypes. Thus,
      DM-deficient mice expressing wild-type Ii chain or p31 alone are both severely
      compromised in their abilities to present peptides. In contrast, double mutants
      expressing the p41 isoform display markedly enhanced peptide-loading
      capabilities, approaching those observed for wild-type mice. The present data
      strengthen evidence for divergent class II presentation pathways and demonstrate
      for the first time that functionally distinct roles are mediated by alternatively
      spliced forms of the MHC class II-associated Ii chain in a physiologic setting.

PMID- 9531265
TI  - Intercellular and intracellular events following the MHC-unrestricted TCR
      recognition of a tumor-specific peptide epitope on the epithelial antigen MUC1.
AB  - We examined the functional and molecular parameters involved in direct TCR
      recognition of a tumor-specific peptide epitope on the tumor Ag MUC1. This
      peptide epitope is tandemly repeated and recognized on the native molecule rather
      than processed and bound to the MHC. Even though the TCR was not MHC restricted,
      intercellular interactions found to facilitate this recognition included
      intercellular adhesion molecule-1/LFA-1, LFA-3/CD2, and class I/CD8.
      Intracellular parameters of MHC-unrestricted CTL activation were examined to
      compare the recognition of the MUC1 epitope presented on synthetic microspheres,
      with the recognition of the native epitope in the context of other molecules on
      the target cells. The epitope on microspheres induced a transient influx of Ca2+
      that was not accompanied by detectable tyrosine phosphorylation of the zeta
      associated protein ZAP-70, whereas recognition of MUC1 epitopes on tumor cells
      caused a sustained Ca2+ influx and ZAP-70 phosphorylation. The transient influx
      of Ca2+ was not sufficient to cause translocation of the nuclear factor of
      activated T cells (NF-AT) into the nucleus or CTL proliferation. In contrast,
      recognition of the MUC1 epitope on tumor cells resulted in full activation of the
      CTL, nuclear translocation of NF-AT, and proliferation. MHC-unrestricted TCR
      triggering, therefore, involves similar intercellular and intracellular events
      that participate in the conventional, MHC-restricted Ag recognition. Direct
      recognition of the MUC1 peptide epitope by the TCR in the absence of presentation
      by the MHC induces a partial signal that is completed by further interactions of
      other receptor/ligand pairs on the surface of the CTL and their target cells.

PMID- 9531266
TI  - CD1.1 expression by mouse antigen-presenting cells and marginal zone B cells.
AB  - Mouse CD1.1 is an MHC class I-like, non-MHC-encoded, surface glycoprotein that
      can be recognized by T cells, in particular NK1.1+ T cells, a subset of alphabeta
      T cells with semiinvariant TCRs that promptly releases potent cytokines such as
      IL-4 and IFN-gamma upon stimulation. To gain insight into the function of CD1.1,
      a panel of nine mAbs was generated and used to biochemically characterize and
      monitor the surface expression of CD1.1 on different cell types. CD1.1 is a
      heavily glycosylated, beta2-microglobulin-associated surface protein. Its
      recognition by a panel of 12 V alpha14-positive and -negative CD1-specific
      alphabeta T cell hybridomas was blocked by two groups of mAbs that bound to
      adjacent clusters of epitopes, indicating that different alphabeta TCRs bind to
      the same region of CD1.1, presumably above the groove. Remarkably, CD1.1 was
      mainly expressed by dendritic cells, B cells, and macrophages, suggesting a
      function in Ag presentation to Th cells. Furthermore, the cell type that
      expressed the highest levels of CD1.1 was the splenic marginal zone B cell, a
      distinct subset of B cells that also expresses CD21 (the C3d receptor) and may be
      involved in natural responses to bacterial Ags. Altogether, the results support
      the idea that CD1.1 may function in recruiting a form of innate help from
      specialized cytokine producer alphabeta T cells to APCs, a role that might be
      important at the preadaptive phase of immune responses to some microbial
      pathogens.

PMID- 9531267
TI  - Tissue-specific recognition of mouse CD1 molecules.
AB  - Although there is evidence that some members of the CD1 gene family may present
      particular types of foreign Ags, such as mycobacterial lipid Ags or synthetic
      hydrophobic peptides, to alphabeta T cells, most CD1 isotypes share the unusual
      property of being recognized by a high frequency of naturally autoreactive
      alphabeta T cells. In the case of mouse CD1.1 and its human counterpart CD1d, a
      significant fraction of the autoreactive T cells express semi-invariant TCRs.
      CD1.1-specific T cells have a restricted tissue distribution and very promptly
      secrete a large panel of potent cytokines, including IL-4 and IFN-gamma, upon
      primary activation through their TCR, suggesting that they might regulate some
      immune responses in these tissues. We show here that their autorecognition of
      mouse CD1.1 is highly dependent upon the cell type in which CD1.1 is expressed.
      For example, some of these T cells only respond to CD1.1 expressed by splenic
      dendritic cells, some respond preferentially to cortical thymocytes, and others
      respond to splenic B cells. Tissue specificity of CD1.1 recognition is also
      observed with various cell lines transfected with CD1.1 cDNA. These results show
      that different CD1.1 self Ags are expressed in different tissues and can be
      specifically recognized by autoreactive T cells. They suggest that CD1.1 may be
      naturally associated with a variety of self ligands that overlap only partially
      in different cell types.

PMID- 9531268
TI  - Characterization of signal transduction through the TCR-zeta chain following T
      cell stimulation with analogue peptides of type II collagen 260-267.
AB  - The immunodominant T cell determinant of type II collagen (CII) recognized by
      DBA/1 mice (I-Aq) is CII 260-267. The aims of this study were to determine the
      role of the amino acid residues within CII 245-270 in T cell signal transduction.
      To that end, we utilized I-Aq-restricted, CII-specific T cell hybridomas and
      examined tyrosine phosphorylation of TCR-zeta following stimulation with either
      wild-type CII 245-270 or a panel of analogue peptides. A variety of patterns
      occurred, ranging from increased phosphorylation of TCR-zeta to either partial or
      a complete abrogation of phosphorylation. Critical substitutions also completely
      abrogated the phosphorylation of ZAP70, a downstream molecule in TCR-zeta
      signaling. Evaluation of the supernatants of the T cell hybridomas for cytokine
      production in response to the peptides revealed a close correlation between the
      induction of phosphorylation of TCR-zeta and the amount of cytokine induced.
      Selected analogue peptides were tested as tolerogens in neonatal mice. Analogues
      that did not induce the phosphorylation of zeta chain, such as B3 (CII 251
      270s263F-->N), were completely unable to induce tolerance, while analogues that
      caused a partial phosphorylation, such as B6 (CII 251-270s267Q-->T) and A3 (CII
      245-270s269P-->A), induced partial tolerance judged by intermediate degrees of
      suppression of arthritis. We conclude that discrete alterations in specific amino
      acid residues of antigenic peptides had profound effects on T cell signaling and
      that the signaling correlated with T cell cytokine secretion and T cell function
      in the induction of tolerance and suppression of arthritis.

PMID- 9531269
TI  - An in vitro model of T cell activation by autologous cytomegalovirus (CMV)
      infected human adult endothelial cells: contribution of CMV-enhanced endothelial
      ICAM-1.
AB  - Cellular immunity is strongly implicated in control of CMV disease; however, many
      mechanistic details remain unresolved. We previously demonstrated T cell
      activation responses to CMV-infected allogeneic endothelial cells (EC),
      suggesting EC as a mediator of CMV response in the transplant recipient. We now
      test the hypothesis that CMV-specific T cell responses can be directly stimulated
      by infected EC in an environment free of potentially confounding allogeneic
      factors. By isolating splenic T cells and gonadal vein endothelial cells (GVEC)
      from individual cadaveric organ donors, we have developed an in vitro model of T
      cell interaction with autologous CMV-infected EC. Proliferation assays
      demonstrated significantly enhanced responses by CMV-seropositive donor-derived T
      cells cocultured with CMV-infected GVEC, as compared with those elicited by
      uninfected cells. Similarly, as determined by limiting dilution analysis of IL-2
      producing cells, T cell response frequencies to infected GVEC were significantly
      greater than to uninfected EC. In contrast, responses of CMV-seronegative donor
      derived T cells were minimal, regardless of CMV status of stimulator GVEC.
      Intriguingly, CD4 responses were observed in spite of the fact that CMV-infected
      EC express no HLA class II. Finally, attenuation of CMV-stimulated T cell
      proliferation observed in the presence of blocking Ab specific for ICAM-1
      suggests a contributing role for CMV-enhanced endothelial ICAM-1 expression in
      the activation response. These studies demonstrate that EC can stimulate
      autologous T cell responses to CMV in the absence of accessory APC and suggest
      potentially novel mechanisms of immune activation.

PMID- 9531270
TI  - Overexpression of the p80 TNF receptor leads to TNF-dependent apoptosis, nuclear
      factor-kappa B activation, and c-Jun kinase activation.
AB  - Because they have distinct intracellular domains, it has been proposed that the
      p60 and p80 forms of the TNF receptor mediate different signals. Several
      signaling proteins have been isolated that associate with either the p60 or the
      p80 receptor. By using TNF muteins specific to the p60 and p80 receptors, we have
      previously shown that cytotoxicity and nuclear factor-kappa B (NF-kappa B)
      activation are mediated through the p60 form of the endogenous receptor. What
      signals are mediated through the p80 receptor is less clear. This study was an
      effort to answer that question. HeLa cells, which express only p60 receptors,
      were transfected with p80 receptor cDNA and then examined for apoptosis, NF-kappa
      B activation, and c-Jun kinase activation induced by TNF and by p60 or p80
      receptor-specific muteins. The p80 mutein, like TNF and the p60 mutein, induced
      apoptosis and activation of NF-kappa B and c-Jun kinase in cells overexpressing
      recombinant p80 receptor but had no effect on cells expressing a high level of
      endogenous p80 receptor. The apoptosis mediated through the p60 receptor was also
      potentiated after overexpression of the p80 receptor, suggesting a synergistic
      relationship between the two receptors. Interestingly, Abs to the p80 receptor
      blocked apoptosis induced by all ligands but by itself activated NF-kappa B in
      the p80-transfected cells. Overall, our results show that the p80 receptor, which
      lacks the death domain, mediated apoptosis, NF-kappa B activation, and c-Jun
      kinase activation, but only when it was overexpressed, whereas endogenous p60
      receptor mediated similar signals without overexpression.

PMID- 9531271
TI  - Superdominance among immunodominant H-2Kb-restricted epitopes and reversal by
      dendritic cell-mediated antigen delivery.
AB  - To examine possible interference patterns between immunodominant CTL Ags, we
      analyzed the response to mixtures of five well-characterized H-2Kb-restricted
      epitopes, each of which had earlier been described as immunodominant within its
      antigenic system. Clear patterns of dominance were observed between peptides in
      the mixture, with the CTL response focusing on the Sendai virus nucleoprotein 324
      332 and vesicular stomatitis virus nucleoprotein 52-59 epitopes. The dominance of
      these epitopes correlated with high CTL availability. Subdominance of the OVA(257
      264) and the MCF1233 murine leukemia virus envelope 574-581 peptides could not be
      explained by inferior ability to bind and stabilize MHC class I molecules.
      Interestingly, immunodominance was broken if the peptide mixture was pulsed on
      bone marrow-derived dendritic cells, a mode of immunization allowing efficient
      recognition of a broader set of specificities. Our results show that
      immunodominance is neither an absolute feature of a given epitope nor does it
      apply only in relation to other epitopes within the same protein, micro-organism,
      or cell. Novel "superdominant" hierarchies emerge in the response against
      multiple "dominant" epitopes. A T cell competition model to explain the data in
      terms of a balance influenced by CTL frequencies and available APC capacity is
      discussed.

PMID- 9531272
TI  - Antibodies to domains II and III of the IL-1 receptor accessory protein inhibit
      IL-1 beta activity but not binding: regulation of IL-1 responses is via type I
      receptor, not the accessory protein.
AB  - The IL-1R accessory protein (IL-1RAcP) plays a role in IL-1R signaling by forming
      a complex with IL-1RI bound to the IL-1 ligand. We identified four hydrophilic
      peptide regions of the extracellular IL-1RAcP that may be available for complex
      formation (peptide 1, 71-83 domain I; peptide 2, 204-211 domain II; peptide 3,
      282-292 domain III; and peptide 4, 304-314 domain III). These peptides were
      synthesized, coupled to keyhole limpet hemocyanin, and used to produce rabbit
      antisera. Each affinity-purified antiserum showed specificity for the respective
      peptide without cross-reactivity. Anti-peptide 2, 3, and 4 recognized surface
      expression of IL-1RAcP on the Th2 D10S cells by FACS and inhibited IL-1-driven
      proliferation. Anti-peptide 4 recognized intact IL-1RAcP and soluble IL-1RAcP.
      Anti-IL-1RAcP-peptide 4, which targets the terminal segment of domain III,
      inhibited 80% of IL-1 beta-driven proliferation of D10S cells. However, these IL
      1RAcP Abs had no effect on the activity of human or mouse IL-1 alpha. Whereas IL
      1 beta down-regulated IL-1RI surface expression (p < 0.05), there was no change
      in the surface expression of IL-1RAcP. Moreover, murine IL-10 increased surface
      expression of IL-1RI, but did not affect expression of IL-1RAcP or the
      proliferation of D10S cells. Steady state levels of mRNA for IL-1RAcP and IL-1RI
      in D10S cells showed a similar pattern to that of surface expression of the
      respective receptors. We conclude that 1) blocking IL-1RAcP inhibits IL-1
      signaling in D10S cells, 2) domains-II and III may be involved in complex
      formation with IL-1RI, 3) IL-1RAcP is not regulated as is IL-1RI in the same
      cells, and 4) IL-1 responsiveness is dependent on the expression of IL-1RI, not
      IL-1RAcP.

PMID- 9531273
TI  - Purified MHC class I and peptide complexes activate naive CD8+ T cells
      independently of the CD28/B7 and LFA-1/ICAM-1 costimulatory interactions.
AB  - T cells play a central role in the initiation, maintenance, and regulation of the
      immune response. Effector responses of T cells are controlled by complex
      combinations of lymphokines and adhesion/costimulatory molecule signals. To
      isolate the effects of specific adhesion/costimulatory molecules and to define
      the minimal molecular requirements of naive CD8+ T cell activation, we have
      developed an APC-free system for stimulation of naive CD8+ T cells. In this
      report, we demonstrate that immobilized MHC class I-peptide complexes can
      activate naive CD8+ T cells from TCR transgenic mice at low cell densities. The
      CD8+ T cells were stimulated to proliferate and secrete IL-2 independently of the
      molecular interactions between CD28/B7.1-B7.2 or LFA-1/ICAM-1 surface receptors.
      Previous reports have shown that CD28 ligation is necessary for late T cell
      survival of APC-stimulated naive CD8+ T cells. Our data suggest that under
      certain specific conditions of high intensity T cell signaling, early activation
      and late cell proliferation can occur independently of APC-derived costimulatory
      signals.

PMID- 9531274
TI  - Inhibitory and stimulatory effects of IL-10 on human CD8+ T cells.
AB  - IL-10 is a well-documented immunosuppressant that inhibits macrophage-dependent
      Ag presentation and CD4+ T cell proliferation in vitro. We report that IL-10
      inhibits alloantigen-specific proliferative responses and induces a long lasting
      anergic state in human purified CD8+ T cells when added concomitantly with the Ag
      in the presence of APC. Moreover, the generation of allospecific cytotoxic
      activity is inhibited by IL-10. These effects are indirect and are mediated
      through inhibition of the costimulatory functions of APC. In contrast, IL-10 has
      no direct inhibitory effects on the proliferation of purified CD8+ T cells
      activated by anti-CD3 mAb and promotes the growth of activated CD8+ T cells in
      combination with low doses of IL-2. Taken together, these results indicate that
      IL-10 has differential effects on CD8+ T cells depending on their state of
      activation, which may explain both the enhancing and inhibitory effects observed
      after IL-10 treatment in different in vivo experimental models.

PMID- 9531275
TI  - Differential susceptibility to activation-induced apoptosis among peripheral Th1
      subsets: correlation with Bcl-2 expression and consequences for AIDS
      pathogenesis.
AB  - It has been proposed that HIV infection is associated with an imbalance in Th1
      and Th2 subsets. Recent reports indicate that Th1 and Th2 effectors differ in
      their susceptibility to activation-induced apoptosis. To determine whether
      increased T cell apoptosis in HIV-infected patients contributes to alterations in
      cytokine synthesis, we performed single-cell analysis of type 1 and type 2
      cytokine production by CD4 and CD8 T cells, simultaneously with detection of
      apoptosis. We demonstrate that a differential alteration in representation of Th1
      subsets, rather than commitment of T cells to secrete Th2 cytokines, occurs
      throughout HIV infection. A significant decrease in the number of IL-2- or TNF
      alpha-producing T cells was observed, whereas those producing IFN-gamma remained
      preserved. Furthermore, there is a gradient of susceptibility to activation
      induced apoptosis (IL-2 < IFN-gamma < TNF-alpha) among the different Th1 subsets.
      This gradient was detected in both CD4 and CD8 subsets, as well as in control
      donors and HIV-infected patients, in whom the susceptibility to apoptosis of IL-2
      and IFN-gamma producers was increased compared with controls. This differential
      intrinsic apoptosis susceptibility of Th1 effectors was found to be tightly
      regulated by Bcl-2 expression. In HIV-infected persons, disappearance of IL-2
      producing T cells was a good indicator of disease progression and was correlated
      with the progressive shrinkage of the CD4+ CD45RA+ T cell compartment and a
      gradual increased susceptibility to activation-induced apoptosis of the IL-2
      producing subset. This close relationship between the CD45RA/CD45R0 ratio, the
      level of type 1 cytokine production, and susceptibility to apoptosis should be
      considered in HIV-infected patients under antiviral or immune-based therapies.

PMID- 9531276
TI  - Discoordinate surface expression of IFN-gamma-induced HLA class II proteins in
      nonprofessional antigen-presenting cells with absence of DM and class II
      colocalization.
AB  - We compared HLA class II expression in a human melanoma line (a nonprofessional
      APC), induced by IFN-gamma or by stable transfection with CIITA, with
      constitutive class II expression in an EBV-transformed B lymphoblastoid cell line
      (a professional APC) from the same donor. IFN-gamma-induced and CIITA-transfected
      melanoma cells expressed DR, DP, and DQ at levels similar to those expressed by
      the professional APC; however, DP and DQ proteins and DM-dependent DR epitopes
      were delayed in appearing on the cell surface when induced by IFN-gamma. The
      delay in cell surface expression of some IFN-gamma-induced class II epitopes was
      observed even though Northern blots demonstrated class II and DM genes to be
      coordinately transcribed and their mRNA levels to be equivalent to that in B
      lymphoblastoid cells. Confocal microscopy suggests that discoordinate cell
      surface expression of class II results from different intracellular trafficking
      for IFN-gamma-induced class II proteins in the melanoma line compared with that
      in professional APCs. Specifically, although DR and DM proteins were present 2
      days after IFN-gamma induction, colocalization of DR and DM proteins
      intracellularly was not apparent in cells at any time after induction. Failure of
      DR and DM proteins to colocalize suggests that IFN-gamma-induced cells lack an
      intracellular MIIC-like compartment. The absence of a compartment containing DR
      and DM to facilitate interaction between the two proteins may account for the
      delayed surface expression of class II epitopes whose formation requires both
      class II and DM.

PMID- 9531277
TI  - Maturation of Qa-1b class I molecules requires beta 2-microglobulin but is TAP
      independent.
AB  - Two conformationally distinct and stable forms of Qa-1b, one strongly associated
      with beta 2-microglobulin (beta 2m) and the other associated with a novel
      molecule, gp44, were observed during immunochemical studies on the expression of
      Qa-1b molecules in mouse spleen cells. Both forms are efficiently processed and
      expressed at the cell surface. However, a large proportion of Qa-1b was found to
      be disulfide linked to gp44 without any detectable beta 2m. In TAP1-deficient
      mice, both forms undergo carbohydrate processing and are expressed on the cell
      surface, suggesting that they may traffic using a pathway not requiring a TAP
      association step. Consistent with this, size exclusion chromatography of newly
      synthesized class I molecules shows that high molecular mass complexes containing
      H-2Kk do not contain Qa-1b. Although Qa-1b can be stably expressed without beta
      2m, there was no maturation of either form in cells from beta 2m-deficient mice
      where heavy chains were rapidly degraded. These results suggest that Qa-1b, like
      most other class I molecules, requires beta 2m for an initial folding step.
      However, beta 2m is not essential for subsequent processing of Qa-1b molecules.

PMID- 9531278
TI  - Kinetics of multivalent antigen DNP-BSA binding to IgE-Fc epsilon RI in
      relationship to the stimulated tyrosine phosphorylation of Fc epsilon RI.
AB  - Multivalent DNP-BSA is commonly used to cross-link anti-DNP IgE bound to Fc
      epsilon RI to stimulate cellular responses, although key features of the binding
      process are unknown. Fluorescence quenching can be used to study the kinetics of
      DNP-BSA binding to FITC-IgE. We observe that DNP-BSA binds more slowly to IgE
      than does an equimolar amount of a monovalent DNP ligand, suggesting that the
      average effective number of DNP groups per BSA is less than one. The binding data
      are well described by a transient hapten exposure model in which most of the DNP
      groups are unavailable for binding but have some probability of becoming exposed
      and available for binding during the time of the binding measurement. Additional
      experiments indicate that, for suboptimal to optimal concentrations of DNP-BSA,
      most of the FITC fluorescence quenching on the cell surface is due to cross
      linking events. With these concentrations at 15 degrees C, the kinetics of FITC
      fluorescence quenching by DNP-BSA correlates with the kinetics of DNP-BSA
      stimulated tyrosine phosphorylation of Fc epsilon RI. At 35 degrees C, the
      phosphorylation kinetics are biphasic during the time period in which cross
      linking continues to increase. Our results establish a quantitative relationship
      between the time-course for cross-linking by multivalent Ag and Fc epsilon RI
      mediated signaling, and they provide the means to predict the kinetics of cross
      linking under a wide variety of conditions.

PMID- 9531279
TI  - CD8+ memory T cells (CD44high, Ly-6C+) are more sensitive than naive cells to
      (CD44low, Ly-6C-) to TCR/CD8 signaling in response to antigen.
AB  - Memory CD8+ T cells from mice previously primed with alloantigen (alloAg) can
      respond in vitro to IL-2 and purified class I alloAg presented on microspheres,
      while no response can be detected using cells from naive mice. Similar results
      have been obtained using cells from OT-1 mice expressing a transgenic TCR that is
      specific for OVA(257-264) (SIINFEKL) peptide bound to H-2Kb. A population of
      resting memory cells (defined on the basis of low forward scatter and CD44high,
      Ly-6C+, CD25-, CD69-surface phenotype) that is present in the OT-1 mice exhibits
      a substantially higher sensitivity to Ag-stimulation than do naive cells
      (CD44low, Ly-6C-) expressing the same TCR. CD44high cells respond vigorously to H
      2Kb immobilized on microspheres and pulsed with peptide, while CD44low cells
      respond weakly and only at high class I density and peptide concentration. The Ag
      presenting surface only has ligands for TCR and CD8 (class I and peptide), thus
      ruling out the possibility that differences are due to ligand binding by other
      adhesion or costimulatory receptors that are expressed at high levels on the
      memory cells. Experiments using anti-TCR mAb as the stimulus and coimmobilized
      non-Ag class I as a ligand for CD8 suggest that the difference between naive and
      memory cells may be at the level of stimulation through the TCR. Thus, in
      addition to expressing increased levels of adhesion receptors that may enhance
      responses to Ag on APCs, memory CD8+ T cells appear to be intrinsically more
      sensitive than naive cells to stimulation through the TCR/CD8 complex.

PMID- 9531280
TI  - Inhibition of an in vitro CD4+ T cell alloresponse using altered peptide ligands.
AB  - In this study, we explore the potential of altered peptide ligands (APLs) to
      modulate the alloresponse of CD4+ T cells using elements of the murine hemoglobin
      (Hb) Ag model. We first demonstrated that the T cell 2.102, specific for the
      Hb(64-76)/I-Ek complex, was alloreactive against splenocytes of the H-2p
      haplotype. Using Ab-blocking and transfection experiments, we further showed that
      this alloreactivity was restricted to the class II molecule I-Ep. We tested a
      panel of APLs previously shown to antagonize the Hb response of 2.102 and found
      that these peptides could also effectively inhibit the alloresponse to I-Ep.
      Importantly, these peptides were able to antagonize the alloresponse of naive T
      cells derived from mice transgenic for the 2.102 TCR, as well as Th1 and Th2 cell
      lines. The antagonism required the presence of both I-Ep and I-Ek on the same
      APC. Our study demonstrates the effectiveness of APLs to antagonize the primary
      alloresponse of specific T cells and provides a basis for the development of
      immunotherapeutics for use in transplantation and immune-mediated diseases.

PMID- 9531281
TI  - In vivo beta-adrenergic stimulation suppresses natural killer activity and
      compromises resistance to tumor metastasis in rats.
AB  - The sympathetic nervous system has been implicated in mediating stress-induced
      alterations in NK cell activity, particularly through stimulation of beta
      adrenergic receptors. However, because catecholamines induce time-dependent
      alterations in the distribution of NK cells, the impact of beta-adrenergic
      stimulation on individual NK cell cytotoxicity is not clear, nor are its
      implications regarding host resistance to metastatic spread. To address these
      issues, we used the beta-adrenergic agonist, metaproterenol (MP), in F344 rats.
      The number of blood NK cells doubled within 10 min of MP administration and
      returned to baseline levels within 1 h. By this time, MP suppressed blood NK
      activity in a dose-dependent manner. Two beta-adrenergic antagonists,
      propranolol, which crosses the blood-brain barrier, and nadolol, which does not,
      blocked this suppression. Corresponding findings were obtained using an NK
      sensitive tumor model, the MADB106. MP caused an up to 10 times increase in the
      number of tumor cells retained in the lungs 1 day after inoculation and a similar
      rise in the number of consequent lung metastases detected 3 wk later. These
      effects were dose dependent and nadolol reversible. NK cells appear to play a
      central role in mediating the tumor-enhancing effects of MP because their
      selective depletion nearly abolished this effect. Overall, our findings suggest
      that independent of the transitory increase in numbers of blood NK cells, in vivo
      beta-adrenergic stimulation suppresses NK activity in the rat. This suppression
      is induced peripherally and can compromise host resistance to NK-sensitive
      tumors. Homologies to studies in humans and clinical relevance are discussed.

PMID- 9531282
TI  - Functional consequences of costimulation by ICAM-1 on IL-2 gene expression and T
      cell activation.
AB  - LFA-1 is a well-recognized adhesion molecule, but its role in providing
      costimulatory signals to T cells has remained controversial. We have compared the
      ability of class II-positive transfectants that do and do not coexpress ICAM-1
      (ProAd and ProAd-ICAM) to activate Ag-specific Th1 clones and naive CD4-positive
      T cells isolated from TCR transgenic mice. Ag presentation by ProAd to Th1 clones
      can induce calcium-dependent signaling events after engagement of the TCR, as
      evidenced by the nuclear localization of the transcription factors NF-AT and NF
      kappaB. Nevertheless, coexpression of ICAM-1 or B7-1 on ProAd is required to
      induce detectable levels of IL-2 gene expression in either Th1 clones or naive T
      cells. In Th1 clones, activation by ProAd-ICAM induces very transient IL-2 mRNA
      expression that does not result in detectable IL-2 secretion or T cell
      proliferation. In naive T cells, the duration of IL-2 mRNA expression is longer,
      allowing for a transient burst of IL-2 protein that is sufficient to drive the
      cells into the cell cycle. In spite of this initial response, Ag presentation by
      ProAd-ICAM is a tolerogenic signal to naive T cells, and responding T cells
      undergo apoptosis 4 to 5 days poststimulation. These data suggest that engagement
      of LFA-1 can provide sufficient costimulatory signals to induce T cell activation
      and IL-2 gene expression, but cannot protect against anergy induction or provide
      for T cell survival.

PMID- 9531283
TI  - Differential regulation of translation and eIF4E phosphorylation during human
      thymocyte maturation.
AB  - Activation of peripheral blood T cells by cross-linking of CD3 results in a rapid
      and substantial rise in translation rates and proliferation, which coincides with
      an increase in the cap-binding protein, eIF4E activity. In contrast, immature
      CD4+ CD8+ double-positive (DP) thymocytes undergo apoptosis in response to anti
      CD3 mAb. We have investigated translation initiation in the response of immature
      thymocytes to activating signals. Activation by anti-CD3 + anti-CD4 of immature
      CD4+ CD8+ DP thymocytes results in a rapid decrease in protein synthesis. In
      contrast, similar treatment of CD4+ or CD8+ single-positive (SP) thymocytes
      results in an increase in protein synthesis. The rate of protein synthesis is
      linked to the phosphorylation status of eIF4E. Following anti-CD3 + anti-CD4
      stimulation, eIF4E phosphorylation strongly decreases in immature DP thymocytes,
      whereas it increases in mature SP thymocytes. The expression of 4E-BP2, a
      specific repressor of eIF4E function, is high in DP cells but decreases during
      maturation, raising the possibility of a role for 4E-BP2 in repressing eIF4E
      phosphorylation. These data provide evidence for differential regulation of the
      translational machinery during T cell development.

PMID- 9531284
TI  - Ontogeny of the heavy chain immunoglobulin repertoire in fetal liver and bone
      marrow.
AB  - We studied the kinetics of maturation of B cell progenitors in the mouse embryo,
      from day 15 of development to birth, both in liver and bone marrow. The analysis
      of Ig heavy chain rearrangements at different time points of late fetal
      development shows that oligoclonal patterns of V(H)-D-J(H) rearrangements are
      detected by day 15 in fetal liver. The pattern is polyclonal and diverse by day
      17; however, 80% of the rearrangements are nonproductive. In bone marrow, the
      pattern of rearrangements is less diverse at birth, although the percentage of
      nonproductive rearrangements approaches adult bone marrow levels (35-40%). After
      day 17 in fetal liver, there is a sudden reversal in the percentage of
      nonproductive rearrangements that reaches 33% at day 19 (birth). Maturation of B
      cells, as measured by the fraction of surface Ig+ in total B220+ cells and the
      presence of N sequence additions in V(H)-D-J(H) joints, occurs in the marrow
      before fetal liver. These results demonstrate that the lymphopoietic environment
      in fetal liver and bone marrow of animals at the same stage of development is
      functionally distinct.

PMID- 9531285
TI  - Phenotype-dependent differences in proteasome subunit composition and cleavage
      specificity in B cell lines.
AB  - We have compared the subunit composition and enzymatic activity of purified 26S
      proteasomes from Burkitt's lymphoma (BL) cells and in vitro EBV-transformed
      lymphoblastoid cell lines (LCLs) of normal B cell origin. Low expression of the
      IFN-gamma-regulated beta low molecular mass polypeptide (Lmp)2, Lmp7, and MECL-1
      was demonstrated in a panel of seven BL lines that express the germinal center
      cell phenotype of the original tumor. Coexpression of Lmp2 and Lmp7 with the
      constitutively expressed subunits delta and MB1 was demonstrated in the BL lines
      by immunoprecipitation and two-dimensional gel fractionation of the 20S
      proteasomes. Coexpression of these subunits correlated with reduced levels of
      chymotrypsin- and trypsin-like activities detected by the cleavage of fluorogenic
      substrates. Down-regulation of Lmp2 and Lmp7 and decreased chymotrypsin- and
      trypsin-like activities were also observed in purified proteasomes from a c-myc
      transfected subline of the ER/EB2-5 LCL that has adopted a BL-like phenotype. A
      synthetic peptide analogue of the immunodominant epitope from the EBV nuclear Ag
      4 (E4416-424Y) was cleaved by proteasomes from BLs and A1, while proteasomes from
      LCLs were inactive. Cleavage of the E4416-424Y peptide was not affected by
      treatment of the BL cells with IFN-gamma despite both significant up-regulation
      of Lmp2 and Lmp7 and reconstitution of chymotrypsin and trypsin-like activities
      against fluorogenic substrates to LCL-like levels. The results demonstrate that B
      cell lines representing different stages of B cell activation and differentiation
      express proteasomes with different subunit compositions and enzymatic activity.
      This may result in the generation of a distinct set of endogenous peptides and
      influence the immunogenicity of these cells.

PMID- 9531286
TI  - CD34+CD38-lin- cord blood cells develop into dendritic cells in human thymic
      stromal monolayers and thymic nodules.
AB  - Thymic dendritic cells (DCs) appear to have distinct biologic and functional
      properties compared with DCs in other tissues. Currently, little is known about
      human thymic DCs because they have been difficult to isolate and culture in
      vitro. Here, we report that human thymic stroma can support the development of
      primitive human hemopoietic stem cells into mature DCs without cytokine or serum
      supplementation. Coculture of CD34+CD38-lineage (lin)- and CD34+CD38+lin-
      umbilical cord blood cells with thymic stromal monolayers induced 43 +/- 17-fold
      and 32 +/- 16-fold expansions, respectively, of umbilical cord blood progenitors
      and also generated large numbers of cells with the morphologic, phenotypic, and
      functional characteristics of mature DCs. These cells expressed class I and class
      II MHC, CD1a, CD2, CD4, CD11c, CD40, CD45, CD80, CD83, and CD86 and were potent
      stimulators of allogeneic T cell activation. Primitive hemopoietic progenitors
      also developed into mature DCs in a novel tissue culture system of thymic nodules
      wherein thymic epithelial cells and fibroblasts were grown in nodular aggregates
      in vitro. These results demonstrate that human thymic stroma efficiently supports
      the development of CD34+CD38-lin- cord blood cells into mature DCs. In addition,
      the culture conditions described in this report are useful systems for studying
      the ontogeny of human DCs in thymic microenvironments.

PMID- 9531287
TI  - In vivo IL-4 responses to anti-IgD antibody are MHC class II dependent and beta 2
      microglobulin independent and develop normally in the absence of IL-4 priming of
      T cells.
AB  - A crucial role for CD1-responsive, MHC class II-unrestricted T cells in the
      generation of T cell IL-4 responses is suggested by the: 1) requirement for IL-4
      to prime in vitro IL-4 responses by naive CD4+ T cells; 2) ability of TCR cross
      linking to induce CD1-responsive T cells, but not conventional naive T cells, to
      produce IL-4; 3) failure of anti-IgD Ab to induce an IL-4-dependent IgE response
      in beta 2-microglobulin-deficient mice, which lack CD1; and 4) reported ability
      of MHC class II-deficient mice to make IgE responses to anti-IgD Ab. In contrast,
      the Ag specificity of cytokine and Ab responses in anti-IgD-injected mice and the
      normal IgE responses made by anti-IgD-treated CD1-deficient mice are difficult to
      reconcile with this view. We now find that the failure of beta 2-microglobulin
      deficient mice to make an IgE response to anti-IgD Ab is caused by their rapid
      degradation of anti-IgD; sustained anti-IgD treatment induces them to make
      relatively normal IL-4 and IgE responses. Furthermore, in our study, MHC class II
      deficient mice make little or no IL-4 or IgE responses to anti-IgD Ab and beta 2
      microglobulin-deficient mice make large in vivo IL-4 responses to anti-CD3 mAb.
      Finally, although IL-4 priming of T cells for IL-4 production is Stat6 dependent,
      Stat6-deficient mice make normal IL-4 responses to anti-IgD. Thus, CD1-responsive
      T cells and other beta 2-microglobulin-dependent T cells are not required to
      prime conventional CD4+ T cells to make IL-4 responses to anti-IgD in vivo; in
      fact, the large IL-4 response made in this system does not require IL-4 priming.

PMID- 9531288
TI  - Asymmetrical phosphorylation and function of immunoreceptor tyrosine-based
      activation motif tyrosines in B cell antigen receptor signal transduction.
AB  - CD79a and CD79b function as transducers of B cell antigen receptor signals via a
      cytoplasmic sequence, termed the immunoreceptor tyrosine-based activation motif
      (ITAM). ITAMs contain two conserved tyrosines that may become phosphorylated upon
      receptor aggregation and bind distinct effectors by virtue of the distinct
      preference of phosphotyrosyl-containing sequences for SH2 domains. To explore the
      function of CD79a and CD79b ITAM tyrosines, we created membrane molecules
      composed of MHC class II I-Ak extracellular and transmembrane domains, and CD79a
      or CD79b cytoplasmic domains in which one or both of the ITAM tyrosines were
      mutated to phenylalanine. Functional analysis revealed that both ITAM tyrosines
      are required for ligand-induced Syk phosphorylation. However CD79a-ITAM and CD79b
      ITAM tyrosine phosphorylations were asymmetrical, with >80% of phosphorylation
      occurring on the N-terminal tyrosine (Y-E-G-L). Thus, these findings suggest that
      following receptor ligation, only a minor proportion of phosphorylated ITAMs are
      doubly phosphorylated and thus can engage Syk. Only the N-terminal ITAM tyrosine
      of CD79a was required for ligand-mediated phosphorylation of the receptor and a
      subset of downstream substrates, including p62, p110, and Shc, and for Ca2+
      mobilization. However, responses mediated through CD79b exhibited a greater
      dependence on the presence of both tyrosines. Neither tyrosine in CD79a or CD79b
      appeared absolutely essential for Src family kinase phosphorylation. These
      results indicate that phosphorylations of the tyrosines in CD79a and CD79b occur
      with very different stoichiometry, and the respective tyrosyl residues have
      distinct functions.

PMID- 9531289
TI  - Epitope-specific antibody response to IgE by mimotope immunization.
AB  - We have previously described a mouse monoclonal anti-human IgE antibody (BSW17)
      capable of recognizing receptor-bound IgE without inducing mediator release from
      human basophils or mast cells. Moreover, immune complexes of IgE and BSW17 are
      not able to bind to the IgE receptor. An initial attempt to map the precise
      epitope recognized by this mAb by using Fc epsilon-derived peptides of variable
      length was unsuccessful. However, by screening random peptide phage display
      libraries we isolated circular nona- and octapeptides specifically recognized by
      BSW17. These constrained peptides mimic at least a part of a conformational
      epitope and are thus called mimotopes. These mimotopes, either phage displayed or
      synthetically synthesized, did not react with any other anti-human IgE antibody
      tested, but efficiently inhibited the binding of human IgE to BSW17 only. The use
      of Rhodol-Green-labeled free cyclic peptide proved that these interactions were
      not carrier dependent. Immunization of rabbits with phage clones displaying the
      specific peptides on the surface induced an anti-human IgE response specific for
      the epitope of BSW17. Therefore, we conclude that such mimotopes or mimotope
      derived peptides might be used for vaccination to induce in vivo a beneficial
      anti-IgE response as a novel immunotherapy.

PMID- 9531290
TI  - Activation of lyn, blk, and btk but not syk in CD72-stimulated B lymphocytes.
AB  - CD72 is a B cell-specific glycoprotein that has been shown to be important for
      activation of mature B cells. Previously we showed that some of the early
      signaling events, such as calcium mobilization and phospholipase-gamma
      activation, were similar in B cell Ag receptor (BCR)- and CD72-stimulated B cells
      and that BCR- but not CD72-mediated early signaling events were blocked by
      protein kinase A activation. The present report shows that CD72 ligation induces
      a variety of tyrosine-phosphorylated proteins, most of which were of the same
      molecular mass as those seen in anti-IgM-treated B cells, except for a 72-kDa
      protein. Further analysis showed that the tyrosine kinases lyn and blk were
      activated in CD72-ligated B cells. Interestingly, the non-src kinase syk was not
      activated in CD72-stimulated cells whereas the tec family kinase btk was
      activated in both CD72- and BCR-stimulated B cells. Furthermore, B cells from xid
      mice were unresponsive to CD72-induced proliferation, indicating an essential
      role for btk in CD72-induced signaling events. Surprisingly, tyrosine
      phosphorylation of phospholipase C-gamma2 was normal in CD72-stimulated cells in
      spite of a lack of activation of syk. Furthermore, B cell proliferation through
      CD72 was blocked by the immunosuppressive agents cyclosporin A and FK506,
      indicating the important role for Ca2+-regulated activation events similar to BCR
      stimulated cells. We propose that btk can substitute for syk in inducing
      phospholipase C-gamma2 tyrosine phosphorylation and initiating calcium
      mobilization in CD72-stimulated B lymphocytes.

PMID- 9531291
TI  - Involvement of C-Abl tyrosine kinase in lipopolysaccharide-induced macrophage
      activation.
AB  - LPS endotoxin-induced macrophage activation is recognized to be important in both
      nonspecific immunity and endotoxin-induced sepsis when excessive macrophage
      stimulation occurs. In this study, we showed that reduction of c-Abl in
      macrophages prevented LPS-induced growth arrest, nitric oxide production and TNF
      alpha secretion by ANA-1 macrophages. These cells continued to grow but later
      underwent apoptosis. Reduction of c-Abl in these cells led to reduced c-Abl
      kinase activity associated with Ran, which recently has been shown to be an LPS
      responsive gene product. Our data suggest that c-Abl tyrosine kinase is one of
      the intermediates downstream of the initial signal transduction event related to
      activation of macrophages by LPS.

PMID- 9531292
TI  - Stimulation of murine B lymphocytes induces a DNA exonuclease whose activity on
      switch-mu DNA is specifically inhibited by other germ-line switch region RNAs.
AB  - The Ig heavy chain class switch in B lymphocytes involves a unique genetic
      recombination that fuses specific regions within the Ig locus and deletes
      intervening sequences. Here we describe a novel exonuclease activity in nuclear
      lysates of B cells in an in vitro assay. This activity was induced in B
      lymphocytes after treatment with either LPSs or CD40 ligand/anti-delta-dextran,
      both of which induce switch recombination, and considerably less activity was
      detected in untreated or anti-delta-dextran-treated B cells, Con A-stimulated
      spleen cells, liver cells, or a number of cell lines. The exonuclease activity
      was dependent on divalent cations, and both 3' and 5' labels were efficiently
      removed from DNA substrates. The presence of RNase A, but not RNase H, inhibited
      exonucleolytic digestion, suggesting that a ribonucleoprotein is responsible for
      the exonucleolysis. The DNA digestion appears to be nonspecific, since DNA
      substrates with either switch-mu or unrelated sequence were hydrolyzed with
      comparable efficiency. Germ-line switch region transcripts (Ig gamma1, Ig gamma3,
      and Ig alpha) strongly inhibited the exonucleolysis of switch-mu DNA but not that
      of unrelated control DNA, while switch antisense RNA or tRNA were much less
      effective inhibitors.

PMID- 9531293
TI  - Identification of the second heparin-binding domain in human complement factor H.
AB  - Complement factor H (fH) regulates activation of the alternative pathway of C,
      reducing the amount of C3b deposited on sialic acid-rich surfaces. Heparin
      binding has been used as a model for examining the sialic acid-binding
      characteristics of fH. We have previously shown that of the 20 short consensus
      repeat (SCR) modules of fH, SCR 7 contains an important heparin binding site, but
      other SCRs also play a role in heparin binding. To localize the other sites, we
      prepared recombinant truncated and SCR deletion mutants of fH and tested them by
      heparin-agarose affinity chromatography. The 5 C-terminal SCRs were found to
      contain a heparin binding site as an SCR 7 deletion mutant of the N terminal 15
      SCRs did not bind heparin, but a construct consisting of SCRs 16-20 was shown to
      bind heparin. Double deletion of SCRs 7 and 20 from fH abrogated binding to
      heparin, indicating that SCR 20 contains a heparin binding site. This finding was
      confirmed with the observation that attachment of SCR 20 to a group of nonbinding
      SCRs produced a heparin-binding protein. A protein consisting of SCRs 19 and 20
      did not bind heparin, whereas SCRs 18-20 did, indicating that, although SCR 20
      contains a heparin binding site, at least two nonspecific adjacent SCRs are
      required. fH-related protein-3 (FHR-3) possesses an SCR homologous to SCR 7 of fH
      and bound heparin, whereas FHR-4, which lacks such an SCR, did not. Thus, fH
      contains two separate heparin binding sites, which are located in SCRs 7 and 20.

PMID- 9531294
TI  - Identification of a domain in human factor H and factor H-like protein-1 required
      for the interaction with streptococcal M proteins.
AB  - The plasma protein factor H (FH) inhibits the alternative pathway of complement
      activation. Previous work has shown that FH binds to group A streptococci and
      that the interaction does not interfere with the complement-inhibitory capacity
      of FH. In this work, we report a molecular analysis of this interaction. In
      absorption experiments with human plasma, M protein-expressing group A
      streptococci bound both FH and FH-like protein-1 (FHL-1), an active 42-kDa splice
      product of the FH-gene transcript comprising the first 7 of its 20 short
      consensus repeat (SCR) domains. rFHL-1 also bound to M protein-expressing
      streptococci, but rFH fragments containing SCR 1-5 or SCR 1-6 did not. rFHL-1
      bound to purified M5 protein with an affinity that was higher than the value
      calculated for the interaction between FH and M5 protein. The binding of
      radiolabeled rFHL-1 to immobilized M5 was blocked completely by unlabeled rFHL-1,
      but was inhibited only partially by SCR 1-6, emphasizing the importance of SCR 7
      for the interaction. In experiments with the FH-related proteins FHR-3 and FHR-4,
      only the former bound to M protein-expressing streptococci, again pointing to an
      involvement of SCR 7, since FHR-3, but not FHR-4, contains a domain that is
      similar to SCR 7. Finally, the interaction between rFHL-1 and purified M5 protein
      was inhibited by heparin, which binds FH via SCR 7. Together, these data indicate
      that the interaction between streptococcal M proteins and FH or FHL-1 requires
      SCR 7.

PMID- 9531295
TI  - Identification of a sequence that mediates promiscuous binding of invariant chain
      to MHC class II allotypes.
AB  - The invariant chain (Ii) shows promiscuous binding to a great variety of MHC
      class II allotypes. In contrast, the affinities of the Ii-derived fragments,
      class II-associated Ii peptides, show large differences in binding to class II
      allotypes. The promiscuous association of Ii to all class II polypeptides
      therefore requires an additional contact site to stabilize the interaction to the
      polymorphic class II cleft. We constructed recombinant molecules containing the
      class II binding site of Ii (CBS) and tested their association with HLA-DR
      dimers. The CBS fused to the transferrin receptor mediates binding of transferrin
      receptor-CBS to class II dimers. Within the CBS, deletion of a sequence N
      terminal to the groove-binding motif abolished binding of Ii to DR. A promiscuous
      class II binding site was identified by reinsertion of the N-terminal residues,
      amino acids 81-87, of Ii into an Ii mutant that lacks the groove-binding segment.
      DR allotype-dependent association of Ii was achieved by insertion of antigenic
      sequences. The promiscuous association, in contrast to the class II allotype
      dependent binding of Ii, is important to prevent interaction of class II dimers
      to nascent polypeptides in the endoplasmic reticulum.

PMID- 9531296
TI  - Several common HLA-DR types share largely overlapping peptide binding
      repertoires.
AB  - The peptide binding specificities of HLA-DRB1*0401, DRB1*0101, and DRB1*0701 have
      been analyzed by the use of large collections of synthetic peptides corresponding
      to naturally occurring sequences. The results demonstrated that nearly all
      peptides binding to these DR molecules bear a motif characterized by a large
      aromatic or hydrophobic residue in position 1 (Y, F, W, L, I, V, M) and a small,
      noncharged residue in position 6 (S, T, C, A, P, V, I, L, M). In addition, allele
      specific secondary effects and secondary anchors were defined, and these
      parameters were utilized to derive allele-specific motifs and algorithms. By the
      combined use of such algorithms, peptides capable of degenerate DRB1*0101,
      DRB1*0401, and DRB1*0701 binding were identified. Additional experiments
      utilizing a panel of quantitative assays specific for nine additional common DR
      molecules identified a large set of DR molecules, which includes at least the
      DRB1*0101, DRB1*0401, DRB1*0701, DRB5*0101, DRB1*1501, DRB1*0901, and DRB1*1302
      allelic products, characterized by overlapping peptide-binding repertoires. These
      results have implications for understanding the molecular interactions involved
      in peptide-DR binding, as well as the genetic and structural basis of MHC
      polymorphism. These results also have potential practical implications for the
      development of epitope-based prophylactic and therapeutic vaccines.

PMID- 9531297
TI  - Spectratyping of TCR expressed by CTL-infiltrating male antigen (HY)-disparate
      allografts.
AB  - Minor histocompatibility Ags (HA) play prominent roles in stimulating allograft
      rejection and are recognized by CTLs that mediate this process. There is limited
      information regarding the sequences of minor HA peptides and the diversity of
      minor HA-specific TCRs. In the case of the male minor HA (HY), a peptide
      presented by H2Db molecules has been sequenced. We have used spectratyping to
      study the diversities of Vbeta usage and beta complementarity-determining region
      3 (CDR3) lengths of TCRs expressed by CTLs that infiltrate HY-disparate skin
      allografts during rejection. Spectratyping of RNA from second- and third-set male
      allografts on CD4-depleted, female recipients showed a reduction in Vbeta usage
      and beta CDR3 length diversity with prominent representation of Vbeta8 genes.
      CDR3 sequences, as a group, were characterized by net negative charges resulting
      from negatively charged residues at positions 5-6 and 10-11. The effects of in
      vivo anti-Vbeta8 Ab treatment on rejection of second-set male allografts were
      investigated. This Ab treatment had no effect on allograft rejection time and
      resulted in increased Vbeta7 usage in recipients with complete Vbeta8 depletion.
      More interestingly, the net charges of beta CDR3s derived from Vbeta8-depleted
      recipients were altered by the inclusion of positively charged and polar residues
      at positions 4-6. These results indicate that Vbeta-specific T cell depletion has
      no effect on HY-disparate allograft survival, but it alters Vbeta usage and
      changes the characteristics of beta CDR3s that facilitate class I:peptide
      recognition.

PMID- 9531298
TI  - Activation of STAT proteins and cytokine genes in human Th1 and Th2 cells
      generated in the absence of IL-12 and IL-4.
AB  - We have shown previously that human CD4+ 45RO- T cells could be primed for a Th2
      phenotype independent of IL-4 if they were activated by anti-CD28 mAb plus IL-2.
      If additional TCR signals were provided, the cells differentiated toward Th1
      independent of IL-12. Here we show that anti-CD28/IL-2-primed Th2 cells expressed
      high levels of activated STAT6, but no cytokine mRNA. Moreover, both Th1 and Th2
      cells expressed active STAT1 and -3, but not STAT2, -4, and -5. Restimulation of
      Th1 or Th2 cells via CD3 plus CD28 induced production of IFN-gamma or IL-4,
      respectively, but did not alter the activation status/DNA binding activity of
      STATs. Addition of IL-4 (or anti-IL-4 mAb) to restimulated Th2 cells did not
      modulate STAT6 activation or IL-4 expression, confirming the full commitment.
      However, Th2 cells remained responsive to IL-12, which repressed STAT6 DNA
      binding but activated STAT4, and this coincided with a suppression of IL-4/IL-5
      and an induction of IFN-gamma. In Th1 cells, IL-12 activated both STAT6 and
      STAT4, and IL-4 activated STAT6, but in both cases the Th1 phenotype remained.
      Together the data show that CD28/IL-2-dependent Th2 priming activated STAT6
      without inducing IL-4 expression. The primed Th cells resembled memory cells and
      produced IL-4 upon the first CD3/CD28 costimulus without detectable modulation of
      STATs. Th2 cells remained responsive to IL-12, which repressed STAT6 DNA binding
      and activated STAT4, and switched the cells to Th1. The effects of IL-12 may
      depend on the commitment of the cells, since IL-12 phosphorylated STAT6 in Th1
      and dephosphorylated STAT6 in Th2 cells.

PMID- 9531299
TI  - Effect of C2-associated carbohydrate structure on Ig effector function: studies
      with chimeric mouse-human IgG1 antibodies in glycosylation mutants of Chinese
      hamster ovary cells.
AB  - The complex biantennary oligosaccharide at Asn297 of IgG is essential for some
      effector functions. To investigate the effect of carbohydrate structure on Ab
      function, we have now expressed mouse-human chimeric IgG1 Abs in Chinese hamster
      ovary (CHO) cells with defined defects in carbohydrate biosynthesis. We had
      previously shown that IgG1 Abs produced in the cell line Lec 1, which attaches a
      high-mannose intermediate carbohydrate, were severely deficient in complement
      activation, showed a slightly reduced affinity for Fc gammaRI, and had a reduced
      in vivo half-life. We have extended these studies by producing the same dansyl
      specific IgG1 in cell lines deficient in attachment of sialic acid (Lec 2) and
      galactose (Lec 8). IgG1-Lec 1, IgG1-Lec 2, and IgG1-Lec 8 all showed varying
      reactivity with a mAb specific for an epitope in the amino terminal region of
      C(H)2, suggesting that the conformations of these proteins were altered by the
      different carbohydrate structures. Functionally, IgG1-Lec 2 and IgG1-Lec 8 were
      comparable to wild type with respect to in vivo half-life, affinity for Fc
      gammaRI, and capacity for complement-mediated hemolysis. While IgG1-Lec 2 was
      essentially identical to wild type in its capacity to interact with individual
      components of the classical complement activation pathway, IgG1-Lec 8
      demonstrated equivalent maximal binding at lower concentrations and was
      preferentially bound by mannose-binding protein. Although IgG1-Lec 1 was
      deficient in activation of the classical pathway, it had a superior capacity to
      activate the alternative pathway. These studies demonstrate that Abs bearing
      C(H)2-linked carbohydrate of differing structures have different functional
      properties.

PMID- 9531300
TI  - Alpha beta T cell response to Toxoplasma gondii in previously unexposed
      individuals.
AB  - The mechanisms by which T cells from previously unexposed hosts respond in vitro
      to certain intracellular pathogens remain to be fully understood. We report and
      characterize the in vitro reactivity to Toxoplasma gondii of human alpha beta T
      cells from T. gondii-seronegative individuals. Resting alpha beta T cells from
      these individuals proliferated in response to PBMC infected with T. gondii or
      pulsed with T. gondii lysate Ags. This was accompanied by an increase in the
      percentage of CD4+ alpha beta T cells. Purified CD4+ alpha beta T cells but not
      CD8+ alpha beta T cells proliferated in response to these T. gondii preparations.
      Both CD4+ alpha beta T cells with naive (CD45RA+) and memory (CD45RO+) phenotypes
      from adults as well as alpha beta T cells from T. gondii-seronegative newborns
      proliferated after incubation with T. gondii. This alpha beta T cell response to
      the parasite was inhibited by anti-HLA-DR mAb and to a lesser degree by anti-HLA
      DQ mAb. Use of paraformaldehyde-fixed PBMC completely abrogated the proliferation
      of alpha beta T cells, indicating the need for processing of T. gondii Ags.
      Analysis of the TCR V beta expression did not show evidence for restriction in
      TCR V beta usage during T. gondii stimulation of alpha beta T cells. Alpha beta T
      cells secreted significant amounts of IFN-gamma after incubation with T. gondii
      infected monocytes. This rapid and remarkable alpha beta T cell response may play
      an important role in the early events of the immune response to T. gondii.

PMID- 9531301
TI  - Stimulation of human T lymphocytes by LPS is MHC unrestricted, but strongly
      dependent on B7 interactions.
AB  - Recently, we have shown that LPS is a potent inducer of human T cell
      proliferation and lymphokine production. However, the activation of T cells by
      LPS has been demonstrated to be monocyte dependent and to require direct cell-to
      cell contact. Here, we investigated the role of monocytes as accessory cells and
      the requirement for costimulatory signals in more detail. We found that the
      accessory cell activity of monocytes during LPS-induced T cell proliferation is
      characterized by the following features: LPS-primed monocytes are competent
      stimulators of T cell proliferation; interaction of LPS with monocytes during the
      priming step is dependent on CD14 and is sensitive to ammonia; monocyte/T cell
      interactions are not MHC restricted but are strongly dependent on interactions of
      CD28 and/or CTLA-4 on T cells and their ligands CD80 and/or CD86 on monocytes.
      CD80 seems to be crucial for the activation of T cells by monocytes, since
      monocytes expressing CD86 but not CD80 after LPS stimulation were unable to
      stimulate T cells; IL-12, at least as a costimulatory factor, but not IL-15, is
      important in LPS-induced T cell proliferation. Taken together, our results
      indicate that LPS acts neither as a mitogen, nor as a superantigen, nor as an Ag.
      The activation of human T cells by LPS requires the help of accessory functions
      by primed monocytes and is MHC unrestricted but needs costimulatory signals via
      CD28 and/or CTLA-4.

PMID- 9531302
TI  - A B7.1-antibody fusion protein retains antibody specificity and ability to
      activate via the T cell costimulatory pathway.
AB  - We describe the construction and characterization of an Ab fusion protein
      specific for the tumor-associated Ag HER2/neu linked to sequences encoding the
      extracellular domain of the B7.1 T cell costimulatory ligand. The Ab domain of
      the fusion molecule will specifically target HER2/neu-expressing tumor cells,
      while the B7.1 domain is designed to activate a specific immune response. We show
      that the B7.1 fusion Ab retained ability to selectively bind to the HER2/neu Ag
      and to the CTLA4/CD28 counter-receptors for B7.1. Specific T cell activation was
      observed when the B7.1 Ab fusion protein was bound to HER2/neu-expressing cells.
      The use of the B7.1 Ab fusion protein may overcome limitations of gene transfer
      and/or standard Ab therapy and represents a novel approach to the eradication of
      minimal residual disease.

PMID- 9531303
TI  - Crucial role of TNF receptor type 1 (p55), but not of TNF receptor type 2 (p75),
      in murine toxoplasmosis.
AB  - TNF-alpha exerts its biologic activity through two distinct receptors, TNF
      receptor type 1 (TNFR1, p55) and TNF receptor type 2 (TNFR2, p75). To analyze
      their function in toxoplasmosis, we orally infected mice genetically deficient
      for TNFR1 (TNFR1(0/0)), TNFR2 (TNFR2(0/0)), or both TNF receptors (TNFR1/2(0/0)),
      as well as wild-type (wt) mice with a low-virulent strain of Toxoplasma gondii.
      TNFR1/2(0/0) and TNFR1(0/0) mice succumbed to toxoplasmosis within 17 and 27
      days, respectively, whereas TNFR2(0/0) and wt mice were equally resistant to
      acute toxoplasmosis. Histopathology attributed death of TNFR1/2(0/0) and
      TNFR1(0/0) mice to a fulminant necrotizing encephalitis. In addition, pneumonia
      contributed to the fatal outcome. The poor prognosis of TNFR1/2(0/0) and
      TNFR1(0/0) mice was reflected by a significantly increased parasitic load in the
      brain and lung as compared with TNFR2(0/0) and wt mice. Immunohistochemistry
      demonstrated a remarkable reduction of inducible nitric oxide synthase protein in
      brain and lung of TNFR1/2(0/0) and TNFR1(0/0) as compared with TNFR2(0/0) and wt
      mice. Reverse-transcribed PCR showed that in contrast to TNFR2(0/0) and wt mice,
      TNFR1(0/0) mice were unable to up-regulate inducible nitric oxide synthase mRNA
      transcripts in the course of infection, whereas intracerebral levels of IFN
      gamma, TNF-alpha, and IL-1beta mRNA transcripts, recruitment of immune cells to
      the brain, and the amount of apoptotic cells in inflammatory foci did not differ
      significantly among the various experimental groups. These results illustrate
      that in Toxoplasma encephalitis, TNF-alpha-mediated immune responses are of
      crucial importance and that signaling through TNFR1, but not TNFR2, provides the
      stimulus required for the induction of protective nitric oxide.

PMID- 9531304
TI  - A bispecific monoclonal antibody directed against both the membrane-bound
      complement regulator CD55 and the renal tumor-associated antigen G250 enhances C3
      deposition and tumor cell lysis by complement.
AB  - Tumor cells may inhibit the induction of a complement-mediated inflammatory
      response through overexpression of membrane-bound regulators of complement
      activation. Therefore, it is of interest to determine the most efficient approach
      to block these membrane-bound complement regulators on tumor cells. In the
      present study, we first generated a bispecific mAb directed against both CD55,
      using the functional blocking mAb MBC1, and the highly expressed HLA class I
      molecule as a model for a tumor-associated Ag, using the mAb W6/32. Tumor cells
      opsonized with bispecific mAb W6/32*MBC1, then exposed to complement and
      subsequently stained for C3 deposition, were assessed by flow cytometric
      analysis. We found that opsonization with W6/32*MBC1 resulted in a 92%
      enhancement of C3 deposition on renal tumor cells as compared with opsonization
      with W6/32 alone and a 17% enhancement of the C3 deposition as compared with
      incubation with a mixture of both parental mAb. Based on these results, we
      developed a bispecific mAb recognizing both CD55 and the relatively low expressed
      renal tumor-associated Ag G250. Increasing concentrations of the bispecific mAb
      G250*MBC1 resulted in a 25 to 400% increase in C3 deposition on renal tumor cells
      as compared with C3 deposition in the presence of the parental mAb G250 alone.
      G250*MBC1 enhanced C3 deposition by 21% in comparison with a mixture of both
      parentals. Furthermore, opsonization of tumor cells with G250*MBC1 rendered these
      cells more sensitive to complement-mediated lysis. In conclusion, the bispecific
      mAb G250*MBC1 induces deposition of C3 and tumor cell lysis more efficiently than
      G250 alone.

PMID- 9531305
TI  - Purification of L-selectin(low) cells promotes the generation of highly potent
      CD4 antitumor effector T lymphocytes.
AB  - Successful adoptive immunotherapy of cancer requires the identification,
      isolation, and expansion of tumor-specific immune effector cells. A reliable
      source of tumor-immune lymphocytes is lymph nodes draining a growing tumor. After
      in vitro stimulation with anti-CD3 and expansion in IL-2, these cells are capable
      of mediating the regression of established tumors. In the absence of further Ag
      stimulation, we recently found that the down-regulation of the homing molecule L
      selectin could serve as a surrogate marker for isolation of specific tumor
      sensitized T cells. The L-selectin(low) (L-selectin-) T cells proliferated more
      vigorously than unfractionated or L-selectin(high) cells. In adoptive
      immunotherapy of established intracranial MCA 205 tumors, L-selectin- cells
      displayed at least 30-fold greater therapeutic efficacy than unfractionated
      cells. L-selectin(high) cells did not demonstrate any antitumor effects.
      Activated L-selectin- cells secreted a number of cytokines, including IFN-gamma,
      IL-2, IL-4, and IL-10, specifically when stimulated with cognate tumor cells.
      Further analysis revealed that CD4 T cells alone mediated tumor regression and
      secreted cytokines. Our results thus demonstrate that the purification of L
      selectin- cells led to the generation of CD4 immune effector cells with unusually
      high therapeutic efficacy against chemically induced tumors. The lack of
      cytotoxicity and the ability to secrete cytokines suggest that these effector CD4
      cells mediate antitumor effects through an indirect mechanism similar to the
      delayed hypersensitivity reaction.

PMID- 9531306
TI  - A critical role for IL-13 in resistance to intestinal nematode infection.
AB  - Mice in which either the IL-4 or the IL-13 gene has been disrupted (IL-4 KO and
      IL-13 KO) were susceptible to infection with the intestinal nematode Trichuris
      muris, whereas their wild-type littermates were highly resistant and expelled the
      parasite. IL-4 KO mice showed diminished Th2-type responses with T. muris
      infection and also failed to produce parasite-specific IgG1 Abs. Although IL-13
      KO mice made reduced Th2-type responses early in infection, they were capable of
      generating strong Th2-type responses at later time points and were unable to
      regulate the magnitude of their Ab isotype response. These results confirm the
      importance of IL-4 in resistance to T. muris and provide the first demonstration
      of an important role for IL-13 in resistance to helminth infection. The IL-13 KO
      mouse had a separate phenotype to that of the IL-4 KO mouse, suggesting that both
      IL-4 and IL-13 play important yet different roles in mediating immunity to
      intestinal helminths.

PMID- 9531307
TI  - Revealing the in vivo behavior of CD4+ T cells specific for an antigen expressed
      in Escherichia coli.
AB  - The clonal expansion and anatomic location of microbe-specific CD4+ Th cells was
      studied by tracking the fate of adoptively transferred DO11.10 TCR transgenic T
      cells specific for OVA peptide 323-339/I-Ad in BALB/c mice infected s.c. with
      Escherichia coli expressing a MalE-OVA fusion protein. After infection, the
      DO11.10 T cells accumulated in the T cell-rich paracortical regions of the
      draining lymph nodes, proliferated there for several days, and then moved into
      the B cell-rich follicles before they slowly disappeared from the lymph nodes.
      These changes occurred despite the fact that viable organisms were never found in
      the lymph nodes. The DO11.10 T cells also accumulated in the s.c. infection site,
      but about 1 day later than in the draining lymph nodes. Injection of purified
      MalE-OVA fusion protein alone induced a transient accumulation of DO11.10 T cells
      in the paracortical regions, but these T cells never entered follicles and the
      mice did not produce anti-OVA antibodies. The DO11.10 T cells that survived in
      animals injected with MalE-OVA alone were hyporesponsive to in vitro Ag
      restimulation and did not produce IL-2 and IFN-gamma, whereas DO11.10 T cells
      from mice infected with MalE-OVA-expressing bacteria produced both lymphokines.
      These results suggest that Ag-specific T cells are first activated in secondary
      lymphoid organs following primary bacterial infection and then migrate to the
      infection site. Furthermore, productive activation of the T cells during the
      primary response is dependent on bacterial components other than the Ag itself.

PMID- 9531308
TI  - Trypanosoma cruzi: Tc52 released protein-induced increased expression of nitric
      oxide synthase and nitric oxide production by macrophages.
AB  - Trypanosoma cruzi target molecules that might regulate the host immune responses
      have not yet been fully identified. In the present study, we demonstrate that the
      parasite-released molecule (Tc52) was able to synergize with IFN-gamma to
      stimulate nitric oxide production by macrophages. This synergistic effect was
      also observed at the level of inducible nitric oxide synthase gene expression.
      Furthermore, Tc52 was also shown to induce gene expression for IL-1alpha, IL-12,
      and IL-10. Moreover, the combination of Tc52 and IFN-gamma down-regulates IL
      1alpha and IL-10 gene expression, but not IL-12. Isotype profiles and Tc52 or
      anti-CD3-induced T cell proliferation were also analyzed, indicating that active
      immunization with Tc52 partially relieves the immunosuppression observed during
      the acute phase of the disease. Moreover, under conditions of experimental
      infection, the Tc52 appears immunologically silent, failing to elicit Ab response
      and lymphocyte proliferation during the initial acute phase infection. Following
      active immunization, Tc52 was capable of stimulating T cell proliferation and Ab
      production with a predominance of IgG1, IgG2a, IgG2b, IgG3, and to a lesser
      extent IgA. Taken together, these results demonstrate that T. cruzi Tc52-released
      Ag could be involved in the immunoregulatory processes. The immune response
      against Tc52 that appears late in the T. cruzi infection may play a role in the
      modulation of its biological function(s).

PMID- 9531309
TI  - Activation of caspase 3 (CPP32)-like proteases is essential for TNF-alpha-induced
      hepatic parenchymal cell apoptosis and neutrophil-mediated necrosis in a murine
      endotoxin shock model.
AB  - Endotoxin (ET)-induced liver failure is characterized by parenchymal cell
      apoptosis and inflammation leading to liver cell necrosis. Members of the caspase
      family have been implicated in the signal transduction pathway of apoptosis. The
      aim of this study was to characterize ET-induced hepatic caspase activation and
      apoptosis and to investigate their effect on neutrophil-mediated liver injury.
      Treatment of C3Heb/FeJ mice with 700 mg/kg galactosamine (Gal) and 100 microg/kg
      Salmonella abortus equi ET increased caspase 3-like protease activity (Asp-Val
      Glu-Asp-substrate) by 1730 +/- 140% at 6 h. There was a parallel enhancement of
      apoptosis (assessed by DNA fragmentation ELISA and terminal deoxynucleotidyl
      transferase-mediated dUTP nick end labeling assay). In contrast, activity of
      caspase 1 (IL-1beta-converting enzyme)-like proteases (Tyr-Val-Ala-Asp-substrate)
      did not change throughout the experiment. Caspase 3-like protease activity and
      apoptosis was not induced by Gal/ET in ET-resistant mice (C3H/HeJ). Furthermore,
      only murine TNF-alpha but not IL-1alphabeta increased caspase activity and
      apoptosis. Gal/ET caused neutrophil-dependent hepatocellular necrosis at 7 h
      (area of necrosis, 45 +/- 3%). Delayed treatment with the caspase 3-like protease
      inhibitor Z-Val-Ala-Asp-CH2F (Z-VAD) (10 mg/kg at 3 h) attenuated apoptosis by 81
      to 88% and prevented liver cell necrosis (< or = 5%). Z-VAD had no effect on the
      initial inflammatory response, including the sequestration of neutrophils in
      sinusoids. However, Z-VAD prevented neutrophil transmigration and necrosis. Our
      data indicate that activation of the caspase 3 subfamily of cysteine proteases is
      critical for the development of parenchymal cell apoptosis. In addition,
      excessive hepatocellular apoptosis can be an important signal for transmigration
      of primed neutrophils sequestered in sinusoids.

PMID- 9531310
TI  - Ribavirin inhibits viral-induced macrophage production of TNF, IL-1, the
      procoagulant fgl2 prothrombinase and preserves Th1 cytokine production but
      inhibits Th2 cytokine response.
AB  - Ribavirin, a synthetic guanosine analogue, possesses a broad spectrum of activity
      against DNA and RNA viruses. It has been previously shown to attenuate the course
      of fulminant hepatitis in mice produced by murine hepatitis virus strain 3. We
      therefore studied the effects of ribavirin on murine hepatitis virus strain 3
      replication, macrophage production of proinflammatory mediators including TNF, IL
      1, and the procoagulant activity (PCA), fgl2 prothrombinase; and Th1/Th2 cytokine
      production. Although ribavirin had inhibitory effects on viral replication (<1
      log), even at high concentrations complete eradication of the virus was not seen.
      In contrast, at physiologic concentrations (up to 500 microg/ml), ribavirin
      markedly reduced viral-induced parameters of macrophage activation. With
      ribavirin treatment, the concentrations of PCA, TNF-alpha and IL-1beta all
      decreased to basal concentrations: PCA from 941 +/- 80 to 34 +/- 11 mU/10(6)
      cells; TNF-alpha from 10.73 +/- 2.15 to 2.74 +/- 0.93 ng/ml; and IL-1beta from
      155.91 +/- 22.62 to 5.74 +/- 0.70 pg/ml. The inhibitory effects of ribavirin were
      at the level of gene transcription as evidenced by Northern analysis. Both in
      vitro and in vivo, ribavirin inhibited the production of IL-4 by Th2 cells,
      whereas it did not diminish the production of IFN-gamma in Th1 cells. In
      contrast, ribavirin had no inhibitory effect on TNF-alpha and IL-1beta production
      in LPS-stimulated macrophages. These results suggest that the beneficial effects
      of ribavirin are mediated by inhibition of induction of macrophage
      proinflammatory cytokines and Th2 cytokines while preserving Th1 cytokines.

PMID- 9531311
TI  - Dominant-negative effect of the lymphocyte function-associated antigen-1 beta
      (CD18) cytoplasmic domain on leukocyte adhesion to ICAM-1 and fibronectin.
AB  - The cytoplasmic domains of LFA-1 (CD11a/CD18) are thought to play an important
      role in the regulation of LFA-1 function. To further elucidate the role of the
      LFA-1 cytoplasmic domains, we transfected chimeric proteins consisting of the
      extracellular domain of CD4 fused with the transmembrane and cytoplasmic domains
      of LFA-1 into T and B cell lines, EL-4 and A20, respectively, and examined their
      effects on LFA-1-mediated cell adhesion. The CD4/18, but not CD4/11a, chimera
      profoundly inhibited LFA-1-mediated cell adhesion to ICAM-1, as well as cell
      spreading following cell adhesion. Unexpectedly, cell adhesion to fibronectin was
      also inhibited by the CD4/18 chimera. The CD4/18 chimera did not affect the
      expression of endogenous LFA-1 or the association of CD11a and CD18. Truncation
      of the carboxyl-terminal 13 amino acid residues of the CD18 cytoplasmic domain of
      the chimera completely abrogated the inhibitory effect on LFA-1. Among these
      amino acid residues, the carboxyl-terminal six residues were dispensable for the
      inhibitory effect in EL-4 cells, whereas it significantly reduced the inhibitory
      activity of CD4/18 in A20 cells. A larger truncation of the CD18 cytoplasmic
      domain was needed to fully abrogate the inhibitory effects of CD4/18 on the
      adhesion to fibronectin. These results show that 1) the CD4/18 chimera has
      dominant-negative effects on cell adhesion mediated by LFA-1 as well as
      fibronectin receptors, and 2) amino acid residues of the CD18 cytoplasmic domain
      involved in the inhibition of LFA-1 seem to be different from those for
      fibronectin receptors.

PMID- 9531312
TI  - Regulation of cell growth by IL-2: role of STAT5 in protection from apoptosis but
      not in cell cycle progression.
AB  - Cytokines play an essential role in the regulation of lymphocyte survival and
      growth. We have analyzed the pathways activated by IE-2 that lead to protection
      from apoptosis and cell proliferation. IL-2 can act as a long-term growth factor
      in 32D cells expressing the wild-type human (hu)IL-2R beta. By contrast, cells
      expressing a truncated form of the huIL-2R beta, which is able to induce Bcl-2
      and c-myc expression but not STAT5 activation, were not protected from apoptosis
      by IL-2; consequently, they could not be grown long term in the presence of IL-2.
      However, IL-2 promoted cell cycle progression in cells bearing the truncated huIL
      2R beta with percentages of viable cells in the G0/G1, S, and G2/M phases similar
      to cells expressing the wild-type huIL-2R beta. Transplantation of a region from
      the erythropoietin receptor, which contains a docking site for STAT5 (Y343) to
      the truncated huIL-2R beta, restored the ability of IL-2 to signal both
      activation of STAT5 and protection from apoptosis. By contrast, transplantation
      of a region from the huIL-4R alpha containing STAT6 docking sites did not confer
      protection from apoptosis. These results indicate that the IL-2-induced cell
      cycle progression can be clearly distinguished from protection from apoptosis and
      that STAT5 participates in the regulation of apoptosis.

PMID- 9531314
TI  - Involvement of NK1+ T cells and their IFN-gamma production in the generalized
      Shwartzman reaction.
AB  - IL-12 (or LPS) priming and subsequent challenge by LPS produces the generalized
      Shwartzman reaction. IFN-gamma induced by IL-12 is a crucial cytokine in the
      priming phase. In vivo depletion of both NK cells and NK1+ alphabeta T cells of
      mice by anti-NK1.1 Ab greatly reduced the elevation of serum IFN-gamma induced by
      IL-12 and significantly reduced mortality after subsequent injection of LPS,
      whereas depletion of NK cells alone by anti-asialo GM1 Ab only partially
      decreased serum IFN-gamma, and lethality was not changed. Cell sorting and
      culture experiments confirmed that liver NK1+ alphabeta T cells of IL-12-injected
      mice produced greater amounts of IFN-gamma than did liver NK cells. MHC class I
      deficient mice of C57BL/6 background, which lack a majority of NK1+ alphabeta T
      cells, produced low amounts of IFN-gamma by IL-12; no mortality was observed
      after the LPS challenge. However, production of TNF-alpha in the second phase
      (after LPS challenge) was not inhibited by depletion of NK cells alone or both
      subsets. IL-12 and subsequent LPS challenge activated NK1+ alphabeta T cells in
      the liver and induced strong cytotoxicity of these cells not only against tumor
      cells (including Fas-negative tumors) but also against a syngeneic hepatocyte
      cell line. Our findings show that IFN-gamma produced by NK1+ alphabeta T cells is
      essential for the IL-12 priming of the Shwartzman reaction, and the
      autoreactivity of NK1+ alphabeta T cells in the liver is involved in the hepatic
      disorders that are sometimes caused by IL-12, LPS, or the generalized Shwartzman
      reaction.

PMID- 9531313
TI  - IL-17 stimulates the production and expression of proinflammatory cytokines, IL
      beta and TNF-alpha, by human macrophages.
AB  - IL-17 is a newly described, T cell-derived cytokine with ill-defined physiologic
      properties. As such, we examined the release of proinflammatory mediators by
      human macrophages in response to recombinant human (rh) IL-17. IL-1beta and TNF
      alpha expression and synthesis were up-regulated by rhIL-17 in a dose (ED50 was
      50 +/- 9 ng/ml)- and time-dependent fashion, with cytokine accumulation reaching
      a zenith after 9 h. Release of IL-6, PGE2, IL-10, IL-12, IL-1R antagonist, and
      stromelysin was also stimulated by rhIL-17. IL-1beta and TNF-alpha mRNA
      expression levels were controlled by rhIL-17 in a complex manner with an initial
      30-min inhibitory phase, and then up-regulation beginning at 1 h and reaching a
      plateau at about 3 h. The latter expression pattern closely mirrored the nuclear
      accumulation of the transcription factor nuclear factor-kappaB. cAMP mimetics
      isobutyl-1-methylxanthine (IBMX), forskolin, PGE2, and cholera toxin reversed
      rhIL-17-induced release of TNF-alpha, but had no consistent effect on induced IL
      1beta synthesis. Induced release of TNF-alpha was also inhibited by
      serine/threonine protein kinase inhibitors KT-5720 (protein kinase A) and
      Calphostin C (protein kinase C), mitogen-activated protein kinase kinase
      inhibitor PD098059, and a nonspecific tyrosine kinase inhibitor, genistein.
      Calphostin C alone abrogated the rhIL-17-induced release of IL-1beta. The
      antiinflammatory cytokines IL-4 (p < 0.01) and IL-10 (p < 0.02) completely
      reversed rhIL-17-stimulated IL-1beta release, while IL-13 and TGF-beta2 were
      partially effective (59 and 43% diminution, respectively). IL-10 exerted a
      significant suppressive effect on IL-17-induced TNF-alpha release (99%, p <
      0.02), while the inhibitory effects of IL-4, IL-13, and TGF-beta2 on TNF-alpha
      secretion were partial (48, 10, and 23%, respectively). The data suggest a
      pivotal role for IL-17 in initiating and/or sustaining an inflammatory response.

PMID- 9531315
TI  - Dual role of ceramide in the control of apoptosis following IL-2 withdrawal.
AB  - Ceramide is largely known as a lipid second messenger with pleiotropic effects.
      Increases in ceramide levels have been related to the onset of apoptosis,
      terminal differentiation, or growth suppression. In this study, addition of
      exogenous C2-ceramide to CTLL-2 cells is found to block IL-2-induced cell cycle
      entry, as well as the apoptosis triggered by IL-2 deprivation. The protective
      effect of C2-ceramide is achieved only in the early stages following cytokine
      deprivation and is related to the inhibition of bcl-xL degradation and the
      induction of a G0 arrest of cells. The same treatment over a longer time when, as
      we demonstrate, ceramide is produced physiologically, enhances cell death by
      apoptosis. The dual effect of ceramide both in protecting from or inducing
      apoptosis is discussed further.

PMID- 9531316
TI  - The multiligand-binding protein gC1qR, putative C1q receptor, is a mitochondrial
      protein.
AB  - A protein of 33 kDa (p33) that tightly binds to the globular domains of the first
      complement component, C1q, is thought to serve as the major C1q receptor (gC1qR)
      on B cells, neutrophils, and mast cells. However, the cellular routing and the
      subcellular localization of p33/gC1qR are unknown. We have performed confocal
      laser-scanning microscopy and found that p33/gC1qR is present in intracellular
      compartments, where it colocalizes with the mitochondrial marker protein,
      pyruvate dehydrogenase. No surface staining for p33/gC1qR on endothelial EA.hy926
      cells was observed. A fusion protein of the p33/gC1qR presequence with green
      fluorescent protein translocated to the mitochondria of transfected COS-7 cells.
      Concomitantly, a 6-kDa portion of the fusion protein was proteolytically removed.
      The 33 amino-terminal residues of the presequence proved sufficient to direct
      reporter constructs to mitochondria. Association of p33/gC1qR with mitoplasts
      indicated that the mature protein of 209 residues resides in the matrix and/or
      the inner membrane of mitochondria. Immunocytochemistry of fetal mice tissues
      revealed a ubiquitous expression of p33/gC1qR, most prominently in tissues that
      are rich in mitochondria. Thus, the candidate complement receptor p33/gC1qR of
      intact cells cannot interact with plasma C1q due to mutually exclusive
      localizations of the components. The functional role of p33/gC1qR needs to be
      reconsidered.

PMID- 9531317
TI  - The receptor for complement anaphylatoxin C3a is expressed by myeloid cells and
      nonmyeloid cells in inflamed human central nervous system: analysis in multiple
      sclerosis and bacterial meningitis.
AB  - The complement anaphylatoxins C5a and C3a are released at the inflammatory site,
      where they contribute to the recruitment and activation of leukocytes and the
      activation of resident cells. The distribution of the receptor for C5a (C5aR) has
      been well studied; however, the receptor for C3a (C3aR) has only recently been
      cloned, and its distribution is uncharacterized. Using a specific affinity
      purified anti-C3aR peptide Ab and oligonucleotides for reverse transcriptase-PCR
      analysis, C3aR expression was characterized in vitro on myeloid and nonmyeloid
      cells and in vivo in the brain. C3aR was expressed by adult astrocytes, astrocyte
      cell lines, monocyte lines THP1 and U937, neutrophils, and monocytes, but not by
      K562 or Ramos. C3aR staining was confirmed by flow cytometry, confocal imaging,
      and electron microscopy analysis. A 65-kDa protein was immunoprecipitated by the
      anti-C3aR from astrocyte and monocyte cell lysates. Our results at the protein
      level were confirmed at the mRNA level. Using reverse transcriptase-PCR, Southern
      blot, and sequencing we found that C3aR mRNA was expressed by fetal astrocytes,
      astrocyte cell lines, and THP1, but not by K562 or Ramos. The astrocyte C3aR cDNA
      was identical with the reported C3aR cDNA. C3aR expression was not detected in
      normal brain sections. However, a strong C3aR staining was evident in areas of
      inflammation in multiple sclerosis and bacterial meningitis. In meningitis, C3aR
      was abundantly expressed by reactive astrocytes, microglia, and infiltrating
      cells (macrophages and neutrophils). In multiple sclerosis, infiltrating
      lymphocytes did not express C3aR, but a strong staining was detected on smooth
      muscle cells (pericytes) surrounding blood vessels.

PMID- 9531318
TI  - IgE versus IgG4 production can be differentially regulated by IL-10.
AB  - Allergen-specific IgE plays a key role in the physiopathology of allergic
      disorders. This IgE response is usually accompanied by a production of IgG4.
      Indirect evidence suggests that IgG4 may not be a sensitizing Ab but, in
      contrast, could be protective. As such, it may be of potential therapeutic
      interest to selectively modulate IgE vs IgG4 production. To date, IgE and IgG4
      switching seems to be controlled by common mechanisms. We report here that IL-10
      has a differential effect on IgE vs IgG4 production by PBMC. IL-10 decreases
      epsilon transcript expression and IgE production induced by IL-4 when added
      during the first 3 days of in vitro culture, suggesting that IL-10 decreases IL-4
      induced IgE switching. In contrast, if added later on B cells that are already
      IgE switched, IL-10 potentiates IgE production. Interestingly, whatever the time
      of addition, IL-10 augments IL-4-induced gamma4 transcript expression and IgG4
      production, with a maximal effect when added during the first 3 days. As IL-10 is
      not a switch factor for IgG4, it is likely that IL-10 enhances IgG4 production by
      potentiating IL-4-induced IgG4 switching. However, IL-10 may also act by
      enhancing the growth and/or differentiation of cells that are already IgG4
      committed. Finally, CD40 ligation reverses the early down-regulating effect of IL
      10 on IgE production. These results are the first evidence of a molecule that
      differentially regulates IgE vs IgG4 production, thereby suggesting the existence
      of a pathway(s) selectively controlling their production.

PMID- 9531319
TI  - Regulation of macrophage phagocytosis of apoptotic cells by cAMP.
AB  - Regulation of macrophage capacity to remove apoptotic cells may control the
      balance of apoptotic and necrotic leukocytes at inflamed foci and the extent of
      leukocyte-mediated tissue damage. Although the molecules involved in the
      phagocytic process are beginning to be defined, little is known about the
      underlying regulatory and signaling mechanisms controlling this process. In this
      paper, we have investigated the effects of treatment of human monocyte-derived
      macrophages with PGs and other agents that elevate intracellular cAMP on
      phagocytosis. PGE2 and PGD2 specifically reduced the proportion of macrophages
      that phagocytosed apoptotic cells. Similar results were obtained with the
      membrane-permeable cAMP analogues dibutyryl-cAMP and 8-bromo-cAMP but not with
      the cGMP analogue dibutyryl-GMP. Consistent with the observation that
      phagocytosis was inhibited by cAMP elevation, treatment of monocyte-derived
      macrophages with PGE2 resulted in rapid, transient increase in levels of
      intracellular cAMP. These effects were not due to nonspecific inhibition of
      monocyte-derived macrophage phagocytosis given that ingestion of Ig-opsonized
      erythrocytes was unaffected. Elevation of cAMP induced morphologic alterations
      indicative of changes in the adhesive status of the macrophage, including cell
      rounding and disassembly of structures that represent points of contact with
      substrate containing actin and talin. These results strongly suggest that rapid
      activation of cAMP signaling pathways by inflammatory mediators regulates
      processes that limit tissue injury and that modulation of cAMP levels represents
      an additional therapeutic target in the control of resolution of inflammation.

PMID- 9531320
TI  - Human eotaxin induces alpha 4 and beta 2 integrin-dependent eosinophil
      accumulation in rat skin in vivo: delayed generation of eotaxin in response to IL
      4.
AB  - The CC chemokine eotaxin, originally purified from bronchoalveolar lavage fluid
      of sensitized guinea pigs following allergen challenge, is a potent eosinophil
      selective chemoattractant. In the present study, we have used (111)In-eosinophils
      and human eotaxin to characterize the profile of chemokine-induced eosinophil
      accumulation in vivo in rat skin. Intradermally injected eotaxin caused a dose
      dependent accumulation of (111)In-eosinophils. Time course studies indicated that
      the response was rapid, since all the accumulation occurred within the first 1 to
      2 h of eotaxin injection. The i.v. administration of anti-intercellular adhesion
      molecule-1, anti-vascular cell adhesion molecule-1, or anti-alpha4 integrin mAbs
      significantly inhibited the eosinophil accumulation induced by 100 pmol of human
      eotaxin by 73, 43, and 67%, respectively. Further, when (111)In-eosinophils were
      pretreated in vitro with anti-alpha4 integrin or anti-beta2 integrin mAbs, or
      with a combination of both mAbs, eotaxin-induced responses in vivo were reduced
      by 52, 49, and 68%, respectively. Eosinophil accumulation induced by intradermal
      IL-4, but not that induced by TNF-alpha or leukotriene B4, appeared to be
      mediated in part by endogenously generated eotaxin. Anti-eotaxin Abs
      significantly inhibited (54%) the later phases (24-28 h) but not the early phase
      (0-4 h) of the response to IL-4. This was consistent with eotaxin mRNA expression
      peaking at 18 h after IL-4 injection. Our findings show that human eotaxin is a
      potent inducer of eosinophil accumulation in vivo, this response being dependent
      on alpha4 integrin/vascular cell adhesion molecule-1 and beta2
      integrin/intercellular adhesion molecule-1 adhesion pathways. Further, the
      eosinophil accumulation in response to IL-4 is partly mediated by endogenously
      generated eotaxin.

PMID- 9531321
TI  - B cell sensitization to helminthic infection develops in utero in humans.
AB  - Human neonates are generally deficient in their ability to generate humoral
      immunity. This deficiency is thought to reflect physiologic immaturity of T and B
      cell function and lack of previous exposure to exogenous Ags. To determine
      whether neonatal humoral immunity can be modified by maternal helminth infection
      during pregnancy, we assessed Ig production by cord blood lymphocytes from
      healthy newborns of mothers living in an area of Kenya where schistosomiasis,
      bancroftian filariasis, and geohelminth infections are endemic. Twelve of 40 and
      17 of 39 cord blood lymphocyte preparations from healthy newborns in Coast
      Province, Kenya, spontaneously made polyclonal IgE (range, 0.15-21 ng/ml) and IgG
      (1.6-10.1 ng/ml) in vitro. In vitro IgE synthesis by cord blood lymphocytes (CBL)
      was, on the average, 10-fold less than that of PBMC of Kenyan mothers (1.1-98
      ng/ml) and was undetectable for CBL from newborns delivered in the United States.
      Schistosome and filarial Ags stimulated a 3- to > 100-fold increase in the
      production of polyclonal IgE and parasite-specific IgG Abs by lymphocytes from 10
      of 40 and 6 of 39 Kenyan newborns, respectively. CBL observed to have helminth Ag
      driven B cell responses were more likely to be from newborns of schistosome- or
      filaria-infected mothers than from uninfected mothers (p < 0.05). These data
      indicate that the human fetus can be sensitized in utero to produce helminth
      specific B cells and that neonatal B cells are intrinsically capable of IgE and
      IgG production.

PMID- 9531322
TI  - Dendritic cells and macrophages are the first and major producers of TNF-alpha in
      pancreatic islets in the nonobese diabetic mouse.
AB  - The nonobese diabetic (NOD) mouse spontaneously develops autoimmune insulin
      dependent diabetes mellitus (IDDM) and serves as an animal model for human type I
      diabetes. TNF-alpha is known to be produced by islet-infiltrating mononuclear
      cells during insulitis and subsequent beta cell destruction and has been
      implicated in the pathogenesis of IDDM. Previously, T cells have been suggested
      as the main source of TNF-alpha in the islet infiltrate. However, on
      immunohistochemical analysis of TNF-alpha expression in islets, we are able to
      show that the staining pattern of TNF-alpha resembles that of dendritic cells
      (DC) and macrophages (Mphi) rather than T cells and that TNF-alpha is expressed
      in islets at the very early stages of insulitis when no T cells are detected. On
      double staining for TNF-alpha and cell surface markers, we can demonstrate that
      TNF-alpha staining clearly correlates with DC and Mphi, whereas there is a poor
      correlation with T cells. This feature was observed at both early and late stages
      of insulitis. TNF-alpha expression was also seen in NOD-SCID islets, in addition
      to a peri-islet infiltration consisting of DC and Mphi, indicating that T cells
      are not required for the early DC and Mphi infiltration and TNF-alpha expression
      in islets. In conclusion, our results show that DC and Mphi are the major, early
      source of TNF-alpha in the NOD islet infiltrate and that TNF-alpha can be
      expressed independently of T cells, indicating that the early DC and Mphi
      infiltration and expression of TNF-alpha are crucial in initiation of diabetes.

PMID- 9531323
TI  - Clonal analysis of intrahepatic B cells from HCV-infected patients with and
      without mixed cryoglobulinemia.
AB  - Clonal rearrangements of Ig heavy chain (IgH) genes and hepatitis C virus (HCV)
      genomic sequences were assayed on intrahepatic B lymphocytes isolated from HCV
      chronically infected patients with and without type II mixed cryoglobulinemia
      (MC). Liver tissue samples from eight patients with and nine without MC were
      subjected to routine histologic studies, immunophenotyping, and genotypic
      analysis including IgH V-D-J region gene rearrangements by PCR. RT-PCR, signal
      amplification by branched DNA assay, and in situ hybridization technique were
      used to detect and quantitate HCV RNA genomic sequences in selected B cells
      purified from each tissue sample. Although HCV infection of intrahepatic B cells
      was shown in all patients both with and without MC, frank B cell monoclonal and
      oligoclonal patterns were found in only three and four patients with MC,
      respectively. No monoclonal profile was seen in the noncryoglobulinemic patients,
      whereas an oligoclonal profile was demonstrated in four of them. No clonalities
      were shown in HCV-unrelated patients matched for age and severity of liver
      disease. No obvious difference in HCV genotype distribution was found in relation
      to the clonal expansion profile. Noncryoglobulinemic patients showing clonal
      expansion in liver tissue had higher titers of serum rheumatoid factor (RF).
      Spontaneous production of RF was shown in cell cultures of intrahepatic B cells,
      suggesting their persistent stimulation in vivo. These data indicate that HCV
      infection of B cells and B cell clonal expansions occur in the liver
      microenvironment and preferentially involve RF-producing cells.

PMID- 9531324
TI  - Active Wegener's granulomatosis is associated with HLA-DR+ CD4+ T cells
      exhibiting an unbalanced Th1-type T cell cytokine pattern: reversal with IL-10.
AB  - Wegener's granulomatosis (WG) is a granulomatous vasculitis that affects the
      upper respiratory tract, lung, and kidney. Since T cells make up a significant
      proportion of cells infiltrating granulomatous lesions in WG, we investigated the
      proliferative response and cytokine profile of T cells from these patients. PBMCs
      were isolated from 12 patients with active WG, 7 patients with inactive disease,
      and 12 healthy normal donors. PBMCs from clinically active WG patients exhibited
      increased proliferation following stimulation with either PMA/ionomycin or anti
      CD2 and anti-CD28, when compared with normal donors. In addition, these PBMCs
      exhibited increased secretion of IFN-gamma, but not of IL-4, IL-5, or IL-10.
      Furthermore, TNF-alpha production from PBMCs and CD4+ T cells isolated from
      patients with WG was elevated, when compared with healthy donors. In further
      studies, we investigated the ability of WG patients' monocytes to produce IL-12
      and showed that both inactive and active patients produced increased amounts of
      IL-12. Finally, the in vitro IFN-gamma production by WG PBMC is inhibited in a
      dose-dependent manner by exogenous IL-10. These data suggest that T cells from WG
      patients overproduce IFN-gamma and TNF-alpha, probably due to dysregulated IL-12
      secretion, and that IL-10 may therefore have therapeutic implications for this
      disease.

PMID- 9531325
TI  - Extracellular granzymes A and B in humans: detection of native species during CTL
      responses in vitro and in vivo.
AB  - Activated CTLs and NK cells induce apoptosis via multiple mechanisms, including
      that termed granule exocytosis. The latter pathway consists of vectorial
      secretion of perforin and a family of granule-associated serine proteases
      (granzymes) to the target cell. To establish whether granzymes are released
      extracellularly during cytolytic reactions in vivo, ELISAs that measure the
      native enzymes were developed and were found to specifically detect granzyme A
      (GrA) and granzyme B (GrB) at picogram concentrations. Low levels of GrA and GrB
      were present in plasma of healthy individuals (GrA, 33.5 pg/ml (median); GrB,
      11.5 pg/ml (median)), whereas significantly higher levels were present in
      patients with ongoing CTL response, i.e., patients suffering from infections by
      EBV or HIV type 1. Markedly elevated levels were also noted in synovial fluid of
      patients with active rheumatoid arthritis. The measurement of soluble granzymes
      should be useful to assess clinical disorders associated with activated CTL and
      NK cells. Furthermore, these results suggest that granzymes mediate biologic
      effects beyond their described role in apoptotic cell death.

PMID- 9531326
TI  - Antifungal therapy in 'bone marrow failure'.

PMID- 9531327
TI  - Cost-effectiveness and quality-of-life assessment of GM-CSF as an adjunct to
      intensive remission induction chemotherapy in elderly patients with acute myeloid
      leukemia.
AB  - We conducted a prospective, randomized, multicentre clinical trial comparing the
      effects and costs of GM-CSF as an adjunct to intensive chemotherapy in elderly
      patients with acute myeloid leukaemia (AML). The patients were randomized to
      either daunomycin-cytosine arabinoside (control arm: n = 161) or daunomycin
      cytosine arabinoside with GM-CSF (GM-CSF arm: n = 157). The primary end-point was
      the effect of GM-CSF on the percentage of complete remissions (CR). Survival
      duration, disease-free survival, quality of life and costs were evaluated
      separately. CR after remission induction treatment was achieved in 55% of the
      patients in the control group and in 56% of the patients in the GM-CSF group (P =
      NS). The duration of survival and disease-free survival at 2 years after
      randomization were estimated at 22% and 19% for the control group and 22% and 14%
      for the GM-CSF group (P = NS). Considering the short-term quality of life, the
      administration of GM-CSF resulted in more problems with regard to depressed mood,
      diarrhoea and rash/eczema. With regard to the long-term quality of life there
      were no significant differences between the two groups. The average costs of the
      primary treatment were higher in GM-CSF-treated patients than in the control
      group, i.e. US$40782 and US$34465, respectively (P < 0.01). The costs during the
      follow-up period did not differ between the two groups. The results of this
      randomized clinical trial indicate that daunomycin-cytosine arabinoside plus GM
      CSF is not a cost-effective treatment strategy when compared with daunomycin
      cytosine arabinoside alone.

PMID- 9531328
TI  - The myeloma cell antigen syndecan-1 is lost by apoptotic myeloma cells.
AB  - Syndecan-1 is a cell membrane proteoglycan that binds extracellular matrix
      components and various growth factors. It is expressed only on malignant plasma
      cells in bone marrow samples from patients with multiple myeloma (MM). Several
      reports have suggested that syndecan-1 was present only on a part of the myeloma
      cells. By using either IL-6-dependent myeloma cell lines or primary myeloma cells
      stained by annexin V, we report here that syndecan-1 was rapidly lost by myeloma
      cells undergoing apoptosis. In the same experimental conditions, expression of
      other cell membrane antigens such as CD38, HLA class-I or CD49d on apoptotic
      myeloma cells was not affected. In addition, we show that syndecan-1 loss was
      independent of activation of the gp130 IL-6 transducer. Dexamethasone induced a
      strong apoptosis of myeloma cells associated with the loss of syndecan-1.
      Finally, by using freshly-explanted tumoural samples, we show that syndecan-1
      rapidly disappeared from myeloma cells in association with induction of
      apoptosis. In conclusion we showed that syndecan-1 is a marker for viable myeloma
      cells which is rapidly lost by apoptotic cells. These results emphasize the
      usefulness of anti-syndecan-1 antibodies to purge tumoural cells from
      haemopoietic grafts or to purify these cells for further manipulations for immuno
      or gene therapies.

PMID- 9531329
TI  - Anti-idiotypic T-cell activation in multiple myeloma induced by M-component
      fragments presented by dendritic cells.
AB  - The monoclonal immunoglobulin (Ig) (M-component) secreted by the tumour plasma
      cells in multiple myeloma (MM) has specific antigenic determinants (idiotypes;
      id) that can serve as tumour-specific antigens. The intact Ig molecule is a weak
      antigen, and small fragments of id protein might be more immunogenic for the
      induction of id-specific immunity. Dendritic cells (DC) have attracted attention
      as the most efficient antigen-presenting cells and promising adjuvants for
      immunotherapy in tumours. In this study the in vitro T-cell response against
      F(ab')2 and Fab fragments, heavy and light chains of the M-component was examined
      in five patients with MM clinical stage I. All fragments were able to stimulate T
      cells but F(ab')2 or Fab fragments and heavy chains induced a stronger response
      than light chains. DC induced a significantly stronger id-specific immune
      response than monocytes. Moreover, with DC as antigen-presenting cells, a
      predominant interferon (IFN)-gamma (type-1 T-cell) response was seen in all
      patients. Both IFN-gamma and interleukin (IL)-4 (type-1 and type-2 T-cell)
      responses were noted when monocytes were used. Our study suggests that DC pulsed
      with idiotypic fragments such as F(ab')2 fragment and heavy chain can be used for
      the induction of type-1 anti-idiotypic T-cell response for immunotherapy in MM.

PMID- 9531330
TI  - Loss of HLA molecules in B lymphomas is associated with an aggressive clinical
      course.
AB  - Major histocompatibility complex class I molecule expression is reduced in some
      malignant tumours permitting escape from immune surveillance and is therefore
      associated with a poor prognosis. Seven cases of non-Hodgkin lymphomas out of 300
      cases of malignant lymphoproliferative disorders totally lacked expression of
      class I molecules as determined by flow cytometry. Clinical data confirmed a
      particular aggressiveness of these cases with frequent extra-nodal involvement, a
      poor international prognostic index, a histological high grade and a poor outcome
      leading to early death in five of the seven cases. A previous diagnosis of
      follicular lymphoma characterized by bcl-2 rearrangements was made in four of
      these cases. HLA-G (class Ib gene), which is reported to bind killer inhibitory
      receptors on NK cells, was absent from the cell surface. However, it was detected
      in three out of four cases at the mRNA level with transcripts encoding soluble
      forms. Additional analysis revealed other abnormalities: class II was negative in
      four out of the seven NHL cases and decreased expression of beta2 microglobulin
      was observed in all cases. Peptide transporter proteins (TAP1) were detected in
      various degrees by immunocytochemistry. These observations showed that total lack
      of class I or class II molecules is a rare event in NHL and is associated with a
      poor prognosis. This could support a role for specific autologous T cells in
      immune surveillance.

PMID- 9531331
TI  - Acute leukaemia in Jehovah's Witnesses.
AB  - The refusal of Jehovah's Witnesses with leukaemia to accept transfusion provides
      a major clinical challenge because of the myelosuppressive effects of
      chemotherapy. Experience in treating five such patients is described. Two
      patients with acute lymphoblastic leukaemia (ALL) achieved remission following
      chemotherapy, the first without transfusion support, the second, a minor,
      receiving transfusion under a court order: the first patient remains in remission
      5 years later, whereas the second subsequently relapsed and died. Of three
      patients with acute myeloid leukaemia (AML), two received chemotherapy: one died
      of anaemia during induction chemotherapy whereas the second eventually consented
      to transfusion but died of refractory leukaemia. The third patient died of
      anaemia despite erythropoietin. We feel Jehovah's Witnesses should not be denied
      antileukaemic therapy if they fully understand the risks involved. Minimizing
      phlebotomy, use of antifibrinolytic agents and growth factors may make
      chemotherapy feasible, especially in ALL where remission may be induced with less
      myelosuppressive agents. The outlook for those with AML treated with conventional
      chemotherapy appears poor; alternative approaches to treatment should be
      considered in these patients.

PMID- 9531332
TI  - Secondary haematological neoplasm after treatment of adult acute lymphoblastic
      leukemia: analysis of 1170 adult ALL patients enrolled in the GIMEMA trials.
      Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto.
AB  - Between 1983 and 1994 the incidence of secondary haematological neoplasms (SHM)
      was evaluated in 1170 new cases of ALL enrolled in the GIMEMA trials. Of the 942
      patients who achieved complete remission (CR); seven developed a SHM: four AMLs
      and three NHLs. The median latency from onset of ALL and of secondary
      haematological neoplasm was 69 months for AML and 61 months for NHL. Three out of
      four patients with secondary AML were unresponsive to the new chemotherapy and
      died, whereas the fourth patient achieved a new CR. Among the three NHL cases,
      two patients are presently alive in CR, whereas the third patient was refractory
      to chemotherapy and died. The relative risk of haematological malignancy among
      the GIMEMA trials population, as compared to that of the Italian Cancer
      Registries, was 15.25-fold higher, and the actuarial estimated cumulative
      proportion of ALL patients with a secondary haematological neoplasm at 5 and 10
      years were 0.59% and 3.63% respectively. The incidence of adult ALL who developed
      a SHM, although apparently lower than in the paediatric ALL series, was higher
      when compared to the normal population. The difference between paediatric and
      adult ALL is probably due to the lack of craniospinal radiotherapy and to the
      lower doses of epipodoxiphyllotoxins used in adult trials. The higher percentage
      of childhood ALL with a prolonged event-free survival could result in an increase
      of secondary neoplasms in these cases, which suggests that secondary
      haematological neoplasms in adult ALL patients are real, although rare, events.

PMID- 9531333
TI  - Association of myelodysplastic changes with purine analogues.
AB  - We describe the occurrence of myelodysplastic changes (hypogranular myeloid
      series and Pelger cells, dyserythropoiesis with ring sideroblasts) in five of 31
      patients with chronic lymphoproliferative disorders after treatment with purine
      analogues. The bone marrows of 31 patients with chronic lymphoproliferative
      disorders before and after treatment with purine analogues were reviewed. The
      majority of patients had received extensive prior treatment, but none had
      dysplastic changes prior to treatment with purine analogues. We suggest that a
      purine analogue may have been responsible for dysplastic change and that further
      follow-up of this phenomenon is warranted.

PMID- 9531334
TI  - Late-onset noninfectious pulmonary complications after allogeneic bone marrow
      transplantation.
AB  - We examined the incidence and clinical outcome of late-onset noninfectious
      pulmonary complications (LONIPC) in a series of 234 patients who underwent
      allogeneic bone marrow transplantation at our institution between April 1982 and
      October 1996. The 179 patients who survived 3 months or more were evaluated.
      Clinical, radiologic, pulmonary function, and pathologic tests were reviewed to
      identify 18 patients (10%) who fulfilled the diagnostic criteria of LONIPC.
      Accordingly, the pulmonary processes included bronchiolitis obliterans (BO, five
      patients), bronchiolitis obliterans with organizing pneumonia (BOOP, three
      patients), diffuse alveolar damage (DAD, one patient), lymphocytic interstitial
      pneumonia (LIP, one patient), and nonclassifiable interstitial pneumonia (NCIP,
      eight patients). Various methods of enhanced immunosuppressive therapy resulted
      in marked durable remission in nine patients (50%) (3/3 with BOOP, 3/8 with NCIP,
      1/1 with DAD, 1/1 with LIP, 1/5 with BO). The presence of chronic graft-versus
      host disease (cGVHD) and prophylaxis for GVHD with cyclosporine and prednisone
      were the only variables significantly associated with the development of LONIPC
      (P = 0.0001 and 0.008, respectively). Regardless of histology, a reduction in the
      forced expiratory volume to < 45% of the predicted range was associated with poor
      response to treatment. These findings suggest a strong association between cGVHD
      and LONIPC and that the risk of LONIPC development may be influenced by the
      particular method of GVHD prophylaxis. Most patients with BOOP or mild airflow
      limitation at diagnosis achieved durable remissions.

PMID- 9531335
TI  - Factors which affect the CFU-GM content of the peripheral blood haemopoietic
      progenitor cell harvests in patients with acute myeloid leukaemia.
AB  - Autologous peripheral blood haemopoietic stem cells (PBSC) were harvested from 30
      patients with de novo acute leukaemia, 29 of whom had entered remission following
      standard chemotherapy. Correlation of CD34+ cells/kg to CFU-GM/kg in the harvests
      was good (correlation coefficient = 0.72, P < 0.001). We demonstrated significant
      associations between the CFU-GM content of the harvest and the following: time to
      platelets >50 x 10(9)/l post final induction course (P < 0.001), days to harvest
      from day 1 of intensification/mobilization (correlation coefficient = -0.73, P <
      0.001), platelets >20 x 10(9)/l at time of harvest (P = 0.02), time to WBC >1.0 x
      10(9)/l post intensification/mobilization (correlation coefficient = -0.70, P <
      0.001), and WBC on day of harvest (correlation coefficient = 0.60, P < 0.001). In
      contrast, we found no relationship between the CFU-GM content of the harvest and
      patient age up to 65 years, presence of absence of coexistent features of
      trilineage myelodysplasia at diagnosis, number of induction courses to remission
      or total number of courses of chemotherapy prior to intensification/mobilization.
      Haemopoietic recovery after reinfusion of PBSC was highly correlated to the
      number of CFU-GM infused (neutrophils >0.5 x 10(9)/l rs = -0.72, P = 0.001;
      platelets >20 x 10(9)/l unsupported rs = -0.71, P = 0.001). Our results show that
      the number of induction courses received, and thus exposure to cytotoxic agents
      received, made no significant difference to subsequent CFU-GM harvest content. We
      collected superior harvests from those patients with faster platelet recovery
      following mobilization therapy. We also found that faster platelet recovery
      following the final induction therapy was a better predictor of the CFU-GM
      harvest following mobilization than was the neutrophil recovery following final
      induction.

PMID- 9531336
TI  - Sustained decrease of peripheral lymphocytes after allogeneic blood stem cell
      aphereses.
AB  - 48 healthy donors underwent peripheral blood stem cell (PBSC) apheresis for
      allogeneic transplantation beginning on day 4 of G-CSF (2 x 5 microg/kg)
      mobilization. In one to four (median two) large-volume mononuclear cell
      aphereses, a median of 55.9 x 10(9) of lymphocytes (range 21.0-109.2 x 10[9])
      were collected, an amount comparable to lymphocyte numbers removed by therapeutic
      lymphaphereses in autoimmune diseases. Mean peripheral lymphocyte counts
      decreased from premobilization values of 2.31 x 10(9)/l to 1.31 x 10(9)/l at a
      median of 34 d (1 month) and 1.53 x 10(9)/l at a median of 327 d (11 months). The
      decrease in peripheral lymphocyte counts was significantly correlated with the
      number of lymphocytes removed and the number of aphereses. Neutrophil and
      platelet counts returned to normal values after 1 month whereas monocyte counts
      and haemoglobin concentrations were significantly decreased at 1 month but not at
      11 months.

PMID- 9531337
TI  - Binding and regulation of thrombopoietin to human megakaryocytes.
AB  - Thrombopoietin (TPO, c-Mpl ligand) is considered to play an important role in the
      regulation of megakaryocytopoiesis and platelet production by activating the
      cytokine receptor c-Mpl. We have examined the binding of 125I-TPO to the human
      megakaryocytic cell line, CMK, and to primary human megakaryocytes. Scatchard
      analysis of TPO binding to its cognate receptor in megakaryocytic cells suggested
      the existence of a single class of c-Mpl receptors. CMK cells exhibited 1223
      receptors per cell with a dissociation constant (Kd) of Kd = 223 pM, whereas
      primary human megakaryocytes exhibited 12140 receptors per cell and a
      dissociation constant of Kd = 749 pM. The pretreatment of CMK cells and primary
      bone marrow megakaryocytes with TPO resulted in a decreased binding of TPO to the
      c-Mpl receptors. This down-regulation was observed within 3 h and was not
      inhibited by cycloheximide. Phorbol ester, an activator of protein kinase C, also
      inhibited TPO binding to the c-Mpl receptors by reducing the number of these
      receptors. The pretreatment of CMK cells with IL-3, IL-6 and DMSO, all of which
      induced the differentiation of CMK cells, did not affect the binding of TPO to
      the c-Mpl receptors. These results suggest an additional mechanism, where protein
      kinase C may help to regulate the binding of TPO to these cells.

PMID- 9531338
TI  - Stimulation of thrombocytopoiesis decreases platelet beta2 but not beta1 or beta3
      integrins.
AB  - The expression of CD29, CD61, CD18 and CD11a on platelets was examined by flow
      cytometry in mice treated with leukaemia inhibitory factor (LIF) or megakaryocyte
      growth and development factor (PEG-rHuMGDF or mpl-ligand). Treatment for 7-14 d
      with PEG-rHuMGDF or LIF increased the number of platelets in peripheral blood
      from 0.9 up to <2.0 x 10(6)/microl. These treatments decreased the expression of
      CD11a and CD18, whereas that of CD29 or CD61 was not markedly changed. Study
      after various doses or times of PEG-rHuMGDF administration indicated that a
      decrease of CD18 expression occurred when platelet counts started to rise.
      Platelet RNA content was increased in mice treated with PEG-rHuMGDF but double
      staining indicated that expression of CD18 was not correlated with RNA content.
      To evaluate integrin expression as a function of time in circulation, platelets
      were biotinylated in vivo. In normal or PEG-rHuMGDF-treated mice, the expression
      of CD29 or CD61 did not change, whereas that of CD18 decreased significantly as a
      function of time in circulation. These findings indicate, firstly, that
      stimulation of thrombocytopoiesis leads to the release of platelets with a low
      content of beta2 integrin and, secondly, that this integrin is also selectively
      lost while in the circulation.

PMID- 9531339
TI  - Serum erythropoietin concentration in anaemia of visceral leishmaniasis (kala
      azar) before and during antimonial therapy.
AB  - Serum erythropoietin (Epo) concentrations and variables of red cell and iron
      status were studied in 27 Sudanese patients who were treated with sodium
      stibogluconate for visceral leishmaniasis (kala-azar). Blood haemoglobin
      increased from 6.4 (+/- 1.7 SD) to 9.5 (+/- 1.4) g/dl during treatment. Serum
      ferritin decreased concomitantly. Serum iron levels were unchanged whereas the
      total iron binding capacity increased slightly. The pre-treatment serum Epo
      concentration in relation to the blood haemoglobin concentration was not as high
      as expected from the one in primary haematological diseases, indicating that
      there is a relative lack of Epo in anaemic kala-azar patients. Serum Epo further
      decreased during stibogluconate therapy. The normal dependence of the serum Epo
      level on the blood haemoglobin concentration was lost during mid-term antimonial
      treatment, but it recovered thereafter. Cell culture studies with the human
      hepatoma cells HepG2 showed that stibogluconate (> or = 30 microg/ml) inhibited
      Epo gene expression. Thus, effective treatment of kala-azar with stibogluconate
      results in improvement of anaemia, although the drug itself may impair Epo
      production.

PMID- 9531340
TI  - Adrenal extramedullary haemopoiesis: diagnosis by a non-invasive method.
AB  - Bilateral adrenal masses were discovered incidentally in a patient with beta
      thalassaemia intermedia. Endocrine investigations showed that the adrenal lesion
      was hormonally inactive. Extramedullary haemopoiesis involving the adrenal glands
      was suggested by the presence of reticuloendothelial tissue as demonstrated by
      bone marrow scintigraphy using Technetium Tc-99m nanocolloid. This report
      illustrates the use of non-invasive functional imaging techniques in the
      management of adrenal 'incidentalomas', which in this case turned out to be a
      rare presentation of extramedullary haemopoiesis.

PMID- 9531341
TI  - Increase in Vdelta1+ gammadelta T cells in the peripheral blood and bone marrow
      as a selective feature of HIV-1 but not other virus infections.
AB  - Dysregulation of T-cell receptor (TCR) alphabeta bearing lymphocytes and an
      increase in Vdelta1+ gammadelta T cells are typical features of HIV-1 infection.
      However, the role of gammadelta T cells remains unclear. Therefore, peripheral
      blood mononuclear cells (PBMC) of 103 HIV-1-infected patients were investigated
      with respect to expression of Vdelta1. These results were compared to the Vdelta1
      expression of bone marrow mononuclear cells (BMMC). In contrast to healthy
      controls, Vdelta1+ cells dominated among both PBMC and BMMC in HIV-1-infected
      patients. Analysis of the coexpression of CD25, CD8, HLA-DR and CD45RO revealed a
      high prevalence of Vdelta1/CD45RO and Vdelta1/HLA-DR double-positive PBMC only in
      HIV-1-infected patients but not in healthy donors. Furthermore, analysis of the
      gammadelta TCR repertoire in patients infected with hepatitis B virus, hepatitis
      C virus, herpes simplex virus (HSV)-1 and HSV-2 showed that the selective
      enhancement of Vdelta1+ cells was restricted to HIV infection and not observed in
      other virus diseases. Our data provide further support for the involvement of
      gammadelta T cells in immunosuppression and progression of HIV infection.

PMID- 9531342
TI  - Neonatal thrombocytopenia: incidence and characterization of maternal
      antiplatelet antibodies by MAIPA assay.
AB  - Neonatal thrombocytopenia (NNT) which is frequent in distressed newborns was
      uncommon in a non-selected population of neonates. The aim of this prospective
      study was to determine the frequency of NNT and, in confirmed NNT, to search for
      maternal antiplatelet antibodies with a monoclonal antibody-specific
      immobilization of platelet antigens (MAIPA) assay. Among the 8388 newborns
      studied, 40 (0.5%, 95% CI 0.3-0.6) had confirmed NNT, which was severe (platelet
      count < 50 x 10[9]/l) in 10 cases (0.12%, 95% CI 0.05-0.20). Antiplatelet
      antibodies were detected in 10/31 studied mothers of thrombocytopenic newborns
      (32.3%): they were alloantibodies in five cases and autoantibodies in five other
      cases. Among these 10 newborns, seven had severe thrombocytopenia and four had
      bleeding complications. As controls, antiplatelet antibodies were also searched
      for in mothers of non-thrombocytopenic newborns: antiplatelet antibodies were
      present in 8.5% (95% CI 5.9-11.7) of thrombocytopenic mothers (n = 400) and 3.2%
      (95% CI 0.7-9.0) of non-thrombocytopenic mothers (n = 95). The difference was
      significant between the control groups and the group of mothers of
      thrombocytopenic newborns. In conclusion, our data indicate that an immune origin
      is frequent in NNT and should be looked for, particularly when the platelet count
      is < 50 x 10(9)/l.

PMID- 9531343
TI  - Platelet activation in patients with sickle cell disease.
AB  - Vascular occlusion and vasculopathy underlie much of the morbidity in patients
      with sickle cell anaemia. Platelets may play a role in this vasculopathy. Samples
      from 43 patients with sickle cell disease (SCD) were examined for evidence of
      platelet activation using fluorescent-labelled monoclonal antibodies and flow
      cytometry. There was increased expression of activation-dependent antigens on the
      platelets from patients with SCD compared to those from both Caucasian and
      African-American controls. In addition, SCD patients had increased levels of
      platelet microparticles. Platelets are activated in patients with sickle cell
      disease. The contribution of platelet activation to sickle cell pathophysiology
      is under active investigation in our laboratories.

PMID- 9531344
TI  - A de novo translocation 46,X,t(X;15) causing haemophilia B in a girl: a case
      report.
AB  - Haemophilia B is an X-linked recessive bleeding disorder caused by mutations in
      the factor IX gene with an incidence of 1:25000-30000. Usually female carriers
      are clinically normal, and severe phenotypic expression of the disease in females
      is extremely rare. In this report we describe a girl with a clinically severe
      course of haemophilia B who had no signs of Turner syndrome or any other
      dysmorphic features. Cytogenetic and molecular studies in the patient and her
      parents showed a de novo translocation 46,X,t(X;15)(q27.1;p11.2) in the patient,
      indicating a possible break near the factor IX gene. The structurally normal X
      chromosome was late replicating and inactivated in all metaphases as shown by
      high-resolution R-banding. By fluorescence in situ hybridization (FISH) with YAC
      and cosmid probes we could further characterize the breakpoint region on the X
      chromosome and the involvement of the factor IX gene.

PMID- 9531345
TI  - Haemostatic factors and prediction of ischaemic heart disease and stroke in
      claudicants.
AB  - Thrombotic risk factors may be important in determining cardiovascular outcome in
      patients with symptomatic peripheral arterial disease. A cohort study with a 6
      year follow-up period was established to determine the relationships between
      haemostatic and rheological factors and incident ischaemic heart disease (IHD)
      and stroke events in patients with peripheral arterial disease. A consecutive
      series of 607 patients with intermittent claudication was examined between 1989
      and 1990 at the Peripheral Vascular Clinic, Royal Infirmary of Edinburgh. Main
      outcome measures were combined fatal and non-fatal stroke, non-fatal myocardial
      infarction (MI), coronary death and total coronary events. A total of 210
      patients died during follow-up. 203 patients did not experience a vascular event
      or deterioration of limb ischaemia. Median levels of fibrinogen, von Willebrand
      factor (VWF), tissue plasminogen activator (t-PA) antigen, fibrin D-dimer and
      whole blood viscosity were significantly higher in those who experienced an event
      compared with those who did not. After adjusting for age and sex, fibrin D-dimer
      was significantly associated with risk of non-fatal myocardial infarction (RR
      1.50, 95% CI 1.09-2.06, P < or = 0.01). Both fibrinogen and fibrin D-dimer were
      associated with risk of total coronary events (P < or = 0.05). The risk of stroke
      was related to baseline levels of t-PA antigen (RR 1.87, 95% CI 1.04-3.34, P < or
      = 0.05) and whole blood viscosity (RR 1.33, 95% CI 1.07-1.65, P < or = 0.01). All
      the relationships became weaker and statistically non-significant after further
      adjustment for cigarette smoking, systolic blood pressure, glucose and baseline
      IHD. The associations of these factors to IHD and stroke may therefore be partly
      related to cardiovascular risk factors, but are likely to be important in the
      pathogenesis of future atherothrombotic events in subjects with peripheral
      arterial disease.

PMID- 9531347
TI  - Gastric cancer associated with acute disseminated intravascular coagulation:
      successful initial treatment with weekly 24-hour infusion of high-dose 5
      fluorouracil and leucovorin.
AB  - Acute disseminated intravascular coagulation (DIC) is a severe complication of
      gastric adenocarcinoma, and most of the patients die within 1-3 weeks. We have
      treated five such patients with an empirical non-myelosuppressive HDFL regimen
      (weekly 24h infusion of high-dose 5-fluorouracil 2600 mg/m2 and leucovorin 300
      mg/m2). Within 2 weeks of starting the treatment the clinical and laboratory
      evidence of acute DIC quickly resolved in all five patients. HDFL not only caused
      no further myelosuppression, but also resulted in normalization of the patient's
      haemogram within a few weeks. Other anti-cancer drugs could then be safely added.
      Three patients had a survival time of more than 6 months. We suggest that HDFL is
      an ideal initial treatment for gastric cancer complicated by acute DIC.

PMID- 9531346
TI  - Risk of recurrent venous thromboembolism in patients with the factor V Leiden
      (FVR506Q) mutation: effect of warfarin and prediction by precipitating factors.
      East Anglian Thrombophilia Study Group.
AB  - Three cohorts of patients with the factor V Leiden mutation were recruited
      independently (heterozygotes, homozygotes and combined thrombophilia). The
      antithrombotic efficacy of oral anticoagulation and the predictive value for
      recurrence of an idiopathic as opposed to a precipitated first event were
      determined. Idiopathic first events occurred at an older age than precipitated
      events (43 v 26 years, LR = 23.31, P < 0.001). None of the patients had a
      recurrent event while on warfarin but the median time to recurrence after
      stopping warfarin was 9 years (95% CI 0.7-17.3 years). The time to recurrence was
      shorter when the first event was idiopathic as opposed to precipitated (3.5 v 13
      years, LR = 4.76, P = 0.029). A calculation of benefit to risk of oral
      anticoagulation with a target INR of 2.5 does not support the use of long-term
      therapy in all patients with the factor V Leiden mutation following a first
      thrombotic event.

PMID- 9531348
TI  - Bleeding symptoms in 27 Iranian patients with the combined deficiency of factor V
      and factor VIII.
AB  - Inherited deficiency of factors V and VIII is the most frequent combined
      coagulation defect. The cases reported so fair are mostly single cases or small
      series from different centres, making it difficult to evaluate the overall
      pattern of clinical manifestations of the combined defect. We examined at a
      single institution 27 Iranian patients. Mucocutaneous and post-surgical bleeding
      were the most frequent clinical manifestations. The presence of two defects did
      not make the severity of bleeding greater than that expected in patients with
      single coagulation defects of similar degrees.

PMID- 9531349
TI  - Positive direct antiglobulin tests and haemolytic anaemia following therapy with
      beta-lactamase inhibitor containing drugs may be associated with nonimmunologic
      adsorption of protein onto red blood cells.
AB  - A high incidence (39%) of positive direct antiglobulin tests (DATs) has been
      reported in patients taking Unasyn [ampicillin sodium plus sulbactam sodium (a
      beta-lactamase inhibitor)]. Three of four patients, with positive DATs, receiving
      Unasyn or Timentin [ticarcillin disodium plus clavulanate potassium (also a beta
      lactamase inhibitor)] developed a haemolytic anaemia (HA) associated with a
      positive DAT, which resolved when drug therapy was stopped. The patients' sera
      did not react with red blood cells (RBCs) in the presence of Unasyn or Timentin,
      but when drug-treated RBCs were tested, patients' sera and normal sera reacted
      equally by indirect antiglobulin test. Following incubation in normal sera, RBCs
      treated with Unasyn, Timentin, Augmentin (amoxicillin + clavulanate), sulbactam
      and clavulanate reacted with anti-human globulin and anti-human albumin (an index
      of non-specific adsorption); RBCs treated with ampicillin and amoxicillin were
      nonreactive. The beta-lactamase inhibitors sulbactam and clavulanate seem to
      cause nonimmunologic adsorption of protein onto RBCs in vitro. This may explain
      the high incidence of positive DATs detected in patients taking Unasyn, which
      contains sulbactam. It was not possible to prove that there was a direct
      association between the nonspecific uptake of protein onto drug-treated RBCs in
      vitro with the positive DATs or the HA.

PMID- 9531350
TI  - Variable expression of CD3-zeta and associated protein tyrosine kinases in
      lymphocytes from patients with myeloid malignancies.
AB  - In myeloid malignancies, T-cell and NK function has been shown to deteriorate
      with transformation from pre-leukaemia to advanced disease. Immune dysfunction in
      solid tumours has been attributed to abnormal signal transduction, possibly
      through altered expression of intracellular components of the TCR/CD3 complex
      (e.g. CD3-zeta), receptors on NK cells and their associated protein tyrosine
      kinases (PTKs; p56lck, p59fyn and ZAP-70). Using a flow cytometric method to
      detect dual-expression of surface proteins and intracellular components of the
      TCR/CD3 complex, we have studied 46 patients with myeloid malignancies. CD3-zeta
      expression was abnormal in 64% of patients, and was more prominent in those with
      advanced disease. Three patients with reduced CD3-zeta were analysed both pre-
      and post-treatment, and recovery of CD3-zeta expression was associated with
      successful remission induction (expression of PTKs was variable and reduced
      levels were seen all disease stages). The results of this study suggest that loss
      of signalling proteins is not a result of direct contact of leukaemic cells with
      lymphocytes per se or the extent of the leukaemia burden, but to a specific
      property of some myeloid malignancies, which is more frequently acquired with
      greater malignant transformation.

PMID- 9531351
TI  - Dendritic cells cultured from mononuclear cells and CD34 cells in myeloma do not
      harbour human herpesvirus 8.
AB  - Dendritic cells (DC) are antigen-presenting cells with the potential to be a
      powerful adjuvant in the immunotherapy of haematological malignancy, including
      myeloma. Recently, human herpesvirus 8 (HHV-8) infection of dendritic cells in
      the long-term bone marrow stromal cultures of patients with myeloma has been
      reported. This finding is of great potential importance regarding oncogenesis in
      myeloma in addition to having significant implications for the use of DC in the
      immunotherapy of this disease. Therefore DC generated from mobilized blood
      mononuclear cells (MO-DC) and purified CD34+ cells (CD34-DC) of myeloma patients
      were examined for the presence of HHV-8 using a sensitive PCR technique. HHV-8
      was not demonstrated in MO-DC or CD34-DC and we conclude that these cells remain
      a suitable vehicle for investigation in the immunotherapy of myeloma.

PMID- 9531352
TI  - Megakaryoblastic transformation of juvenile myelomonocytic leukaemia.

PMID- 9531353
TI  - Quantitation of hepatitis G virus RNA in allogeneic bone marrow transplant
      recipients. Stem Cell Transplantation Team.

PMID- 9531354
TI  - Lack of clonal BCRA2 gene deletion on chromosome 13 in chronic lymphocytic
      leukaemia: an update of recent scientific reports.

PMID- 9531355
TI  - A new case of therapy-related acute myeloid leukaemia with t(8;16)(p11;p13)

PMID- 9531356
TI  - Human herpesvirus 8 in premalignant and cancerous skin lesions in a Japanese
      patient with adult T-cell leukaemia.

PMID- 9531357
TI  - Node-positive prostatic cancer: taps or a call to arms?

PMID- 9531358
TI  - The nature of arterial restenosis after angioplasty.

PMID- 9531359
TI  - Ten-year outcomes for pathologic node-positive patients treated in RTOG 75-06.
AB  - PURPOSE: This study was conducted to see what fraction of prostate cancer
      patients with biopsy-proven nodes are free of cancer 10 years after radiation
      treatment. METHODS AND MATERIALS: RTOG protocol #75-06 included 90 patients with
      biopsy-proven pelvic nodal involvement treated with radiation. They have been
      continuously follow-up since treatment. When feasible, current prostate-specific
      antigen (PSA) levels have been solicited from patients clinically cancer-free (no
      evidence of disease, NED) at 10 years, to confirm cure. RESULTS: The 10-year
      survival was 29%, the 10-year clinical NED survival 7%. PSA levels were obtained
      in 2 of 5 10-year clinical NED patients, they were both less than 0.8 ng/ml. The
      2 proven cures were both clinical stage T-3, Gleason Score 6 and 8, and had 2 and
      1 positive nodes, respectively. Multivariate analysis showed Gleason sum was
      significantly associated with clinical survival without disease. CONCLUSION: A
      small fraction of node-positive patients are cured at 10-year follow-up by
      radiation therapy (2 of 90 with PSA +3 of 90 by clinical endpoints). Innovative
      treatment programs should be directed at node-positive patients in an effort to
      improve the fraction cured.

PMID- 9531360
TI  - Impact of surgical staging in evaluating the radiotherapeutic outcome in RTOG #77
      06, a phase III study for T1BN0M0 (A2) and T2N0M0 (B) prostate carcinoma.
AB  - PURPOSE: To evaluate survival and time to metastatic disease in patients treated
      for localized prostatic carcinoma in a Phase III radiotherapy (RT) protocol,
      Radiation Therapy Oncology Group (RTOG) 77-06. Patients with T18N0M0 (A2) or
      T2N0M0 (B) disease after lymphangiogram (LAG) or staging laparotomy (SL) were
      randomized between prophylactic radiation to the pelvic lymph nodes and prostatic
      bed vs. prostatic bed alone. The outcome of both treatment arms, as well as a
      comparison of the LAG group, to that of the SL group, are updated. METHODS AND
      MATERIALS: A total of 449 eligible males were entered into RTOG protocol 7706
      between 1978 and 1983. Lymph node staging was mandatory but at the physician's
      discretion; 117 (26%) patients had SL, while 332 (74%) had LAG. Follow-up was a
      median of 12 years and a maximum of 16 years. For those randomized to receive
      prophylactic pelvic lymph nodal irradiation, 45 Gy of megavoltage RT was
      delivered via multiple portals in 4.5-5 weeks, while all patients received 65 Gy
      in 6.5-8 weeks to the prostatic bed. RESULTS: There was no significant difference
      in survival whether treatment was administered to the prostate or prostate and
      pelvic lymph nodes. The SL group had greater 12-year survival than the LAG group
      (48% vs. 38%, p = 0.02). Disease-free survival was statistically significant,
      with 38% for the SL group vs. 26% for the LAG group (p = 0.003). Bone metastasis
      was less common in the SL group (14%) than the LAG group (27%) (p = 0.003).
      CONCLUSION: At 12-year median follow-up, there still was no survival difference
      in those patients treated prophylactically to the pelvic nodes and prostatic bed
      vs. the prostatic bed alone. Those patients not surgically staged with only LAG
      for lymph node evaluation were less accurately staged, as reflected by a
      statistically significant reduced survival and earlier metastases.

PMID- 9531361
TI  - Urinary incontinence in patients who have a TURP/TUIP following prostate
      brachytherapy.
AB  - PURPOSE: To determine urinary morbidity in patients who have transurethral
      resection of the prostate (TURP) after 125I brachytherapy. MATERIALS AND METHODS:
      A total of 109 patients with Stage T1-T2 prostatic carcinoma were treated with
      125I implantation from 1991 through 1995. Ten patients underwent
      TURP/transurethral incision of the prostate (TUIP) after brachytherapy to relieve
      urinary obstruction refractory to nonsurgical management. RESULTS: Patients who
      developed refractory urinary retention had a slightly larger preimplant prostate
      volume than those who did not (62 vs. 54 ml; p = 0.16). Seven of the 10 patients
      developed some degree of permanent urinary incontinence following TURP/TUIP.
      Urinary incontinence was mild in three patients [Late Effects Normal Tissue
      Radiation Oncology Group (LENT) score = 1] and severe in four additional patients
      (LENT score = 3). There was no obvious relationship between the degree of
      incontinence and use of TURP vs. TUIP, amount of tissue resected, or time between
      brachytherapy and TURP/TUIP. In five patients for whom detailed urethral
      radiation dose information was available, the doses were higher than generally
      recommended. CONCLUSION: Permanent urinary incontinence is common in patients who
      require a TURP or TUIP after prostate brachytherapy. Its cause is apparently
      multifactorial and may include the degree of physical damage to the urinary
      sphincters and the radiation dose to the urethral region.

PMID- 9531362
TI  - Prognostic biomarker study in pathologically staged N1 non-small cell lung
      cancer.
AB  - PURPOSE: The prognostic influence of 6 biomarkers correlated to histologic
      subtypes of non-small cell lung cancer (NSCLC) on loco-regional control, overall
      survival, disease-free survival (DFS), and distant disease control (DDC) rates,
      all measured at 5 years, were examined. MATERIALS & METHODS: Cell blocks from the
      primary tumors of 137 patients with pathologically staged N1 NSCLC at MDACC were
      analyzed by 6-biomarker status correlated to histological subtypes and their
      outcomes. RESULTS: The ranges of biomarker values were as follows: apoptotic
      index, 0.2-2.8%; mitotic index, 0-1.8%; the proportion of cells in S+G2M, 3-36%;
      p53 status, 0-100%; Ki-67, 0-9.3%; DNA index, 1.0-2.74. Subtypes of 137 cases
      from the postoperative pathology specimen showed that 74 patients had squamous
      carcinoma and 63 patients had adenocarcinoma. Mean and median lengths of follow
      up were 4.21 years and 2.43 years, respectively. Patients with squamous cell
      carcinoma (SCC) had a better 5-year survival (p = 0.006), DFS (p = 0.002), and
      distant metastasis control (p = 0.002) than patients with adenocarcinoma (AC).
      Among patients with AC, the DNA index was a significant predictor of 5-year DFS
      (p = 0.02), DDC rate (p = 0.04), and local-regional control (p < 0.05). Higher
      apoptosis (p = 0.03) and mitosis indices (p = 0.03) were also univariate
      predictors of increased distant disease among patients with AC. Multivariate
      analysis of patients with AC revealed that the DNA index and Ki-67 were the only
      significant independent predictors of distant metastasis (p < 0.04 and p < 0.02,
      respectively) and DFS (p < 0.04 for both). Among patients with SCC, univariate
      analysis showed that S+G2M proportion (p < 0.05) and Ki-67 levels (p < 0.02) were
      significant predictors for local-regional control; for SC, multivariate analysis
      showed that only mitosis was a significant predictor in this case for overall
      survival (p < 0.04). CONCLUSION: Spontaneous apoptotic index and Ki-67 were
      significantly higher in SC than in AC. Patients with SC had less distant
      metastasis better DFS and overall survival than those with AC. Multivariate
      analysis revealed that DNA index and Ki-67 status were significant predictors for
      DDC and DFS in patients with AC, but only mitotic index was a significant
      predictor of overall survival for patients with SCC.

PMID- 9531363
TI  - Dose-response relationship for prophylactic cranial irradiation in small cell
      lung cancer.
AB  - PURPOSE: To determine the dose-response relationship for prophylactic cranial
      irradiation (PCI) in small cell lung cancer, to quantify the growth kinetics of
      subclinical metastases, and to determine the influence of time-delay in
      initiating PCI on its utility. METHODS AND MATERIALS: Published reports of brain
      relapse rates in small cell lung cancer with and without PCI were collected. The
      reduction in brain relapse rate as a function of radiation dose was analyzed. The
      time interval between treatment of the primary tumor and the initiation of PCI
      was analyzed as a factor potentially influencing dose-response. RESULTS: A
      shallow dose-response curve without any threshold in the dose intercept was
      demonstrated for control of subclinical brain metastases in "early PCI" (delay
      between initiation of treatment for primary tumor and PCI less than 60 days). By
      contrast "late PCI" (delay over 60 days) was associated with a significant
      displacement of the dose intercept. Doses over 30-35 Gy in 2-Gy fractions did not
      result in a further reduction in brain relapse rate, but there were too few high
      dose studies to draw any definite conclusion. CONCLUSIONS: The nearly linear dose
      response relationship for reduction in brain relapses demonstrated for "early
      PCI" in the range of doses from zero up to 35 Gy given in 2-Gy fractions supports
      the model of a fairly logarithmically uniform distribution of metastatic cell
      number within a series of patients. When PCI is delayed, a significant threshold
      in dose-response was observed, consistent with a fast growth rate of untreated
      subclinical brain metastases from small cell lung cancer. The exact shape and
      locations of dose-response curves is not well established by this retrospective
      analysis of diverse data. A high probability of eliminating brain relapses
      following PCI requires a dose of about 30-35 Gy in 2-Gy fractions. Control rates
      in brain can be enhanced if PCI is applied early.

PMID- 9531364
TI  - Feasibility and efficacy of external beam radiotherapy after hyperthermic
      isolated limb perfusion with TNF-alpha and melphalan for limb-saving treatment in
      locally advanced extremity soft-tissue sarcoma.
AB  - PURPOSE: Hyperthermic isolated limb perfusion (HILP) with tumor necrosis factor
      alpha (TNF-alpha), interferon-gamma (IFN-gamma), and melphalan is associated with
      a dramatic antitumor effect in locally advanced extremity soft-tissue sarcomas
      (STS). The aim of this study was to demonstrate the feasibility and efficacy of
      adjuvant radiotherapy after HILP with TNF-alpha, IFN-gamma, and melphalan and
      delayed surgical resection. METHODS AND MATERIALS: Between 1991 and 1995, 34
      patients--16 males and 18 females, median age 50 (range 18-80) years--underwent
      HILP for locally advanced extremity STS. Resection of the residual tumor mass was
      performed in most patients after 6-8 weeks. Fifteen patients with
      histopathological viable tumor after resection received adjuvant 60-70 Gy
      external beam radiotherapy (EBRT) (44%, HILP + EBRT group). Nineteen patients
      received HILP without adjuvant EBRT (56%, HILP-only group). Five patients in the
      HILP-only group had also distant metastases (15%) and received HILP as a
      palliative treatment. Treatment morbidity, local recurrences, and regional and
      distant metastases were scored. RESULTS: During a median follow-up of 34 months
      (range 8-54), limb salvage was achieved in 29 patients (85%): 14 patients after
      HILP + EBRT and 15 patients after HILP only. None of the patients from the HILP +
      EBRT group developed local recurrences; however, five patients from the HILP-only
      did (26%) (p < 0.05). Regional metastases were observed in one patient from the
      HILP + EBRT group (7%) and in two patients from the HILP-only group who were
      treated with curative intent (14%). Distant metastases occurred in four patients
      after HILP + EBRT (27%) and in four patients after HILP only with curative intent
      (29%). The mean morbidity (subjective, objective, medical management, and
      analytical evaluation) score in both groups was, respectively, 0.33 for skin and
      subcutaneous tissue and for muscle and soft tissue, 0.34 (HILP + EBRT group) and
      0.33 (HILP-only group). CONCLUSION: Adjuvant EBRT after HILP with TNF-alpha, IFN
      gamma, and melphalan and delayed tumor resection of locally advanced extremity
      STS is feasible and may increase local tumor control without increasing treatment
      morbidity.

PMID- 9531365
TI  - Magnetic resonance thermometry during hyperthermia for human high-grade sarcoma.
AB  - PURPOSE: To determine the feasibility of measuring temperature noninvasively with
      magnetic resonance imaging during hyperthermia treatment of human tumors.
      METHODS: The proton chemical shift detected using phase-difference magnetic
      resonance imaging (MRI) was used to measure temperature in phantoms and human
      tumors during treatment with hyperthermia. Four adult patients having high-grade
      primary sarcoma tumors of the lower leg received 5 hyperthermia treatments in the
      MR scanner using an MRI-compatible radiofrequency heating applicator. Prior to
      each treatment, an average of 3 fiberoptic temperature probes were invasively
      placed into the tumor (or phantom). Hyperthermia was applied concurrent with MR
      thermometry. Following completion of the treatment, regions of interest (ROI)
      were defined on MR phase images at each temperature probe location, in bone
      marrow, and in gel standards placed outside the heated region. The median phase
      difference (compared to pretreatment baseline images) was calculated for each
      ROI. This phase difference was corrected for phase drift observed in standards
      and bone marrow. The observed phase difference, with and without corrections, was
      correlated with the fiberoptic temperature measurements. RESULTS: The phase
      difference observed with MRI was found to correlate with temperature. Phantom
      measurements demonstrated a linear regression coefficient of 4.70 degrees phase
      difference per degree Celsius, with an R2 = 0.998. After human images with
      artifact were excluded, the linear regression demonstrated a correlation
      coefficient of 5.5 degrees phase difference per degree Celsius, with an R2 =
      0.84. In both phantom and human treatments, temperature measured via corrected
      phase difference closely tracked measurements obtained with fiberoptic probes
      during the hyperthermia treatments. CONCLUSIONS: Proton chemical shift imaging
      with current MRI and hyperthermia technology can be used to monitor and control
      temperature during treatment of large tumors in the distal lower extremity.

PMID- 9531366
TI  - The role of radiation therapy in the management of dermatofibrosarcoma
      protuberans.
AB  - PURPOSE: To evaluate the outcome for dermatofibrosarcoma protuberans treated with
      conservation surgery and radiation therapy. METHODS AND MATERIALS: A
      retrospective review was performed of 19 consecutive patients with pathologically
      confirmed dermatofibrosarcoma protuberans who received radiation as an adjuvant
      to surgical resection. RESULTS: The patients ages ranged from 19-76 years
      (median, 40 years); 12 were men. Lesions were located on the trunk in 8, in the
      head and neck area in 7, and in an extremity in 4. Tumor size ranged from 1.2 to
      15 cm (median, 4 cm). Ten patients had at least 1 prior recurrence following
      earlier resection. Two patients received preoperative radiation to 50 Gy in 5
      weeks. Sixteen patients underwent resection followed by radiation (6 of these had
      positive resection margins). In another patient, the tumor regrew rapidly after
      resection and definitive radiation was delivered for gross disease. The 6
      patients with positive microscopic margins received a median dose of 60 Gy, as
      did the 10 with negative margins. The 1 patient with gross disease received 65
      Gy. At a median follow-up of 6 years, the only patient to develop local
      recurrence was treated with definitive radiotherapy for gross disease. Actuarial
      local control was 95% at 10 years. CONCLUSION: Dermatofibrosarcoma protuberans is
      a radioresponsive tumor and radiation to doses of 50-60 Gy should be considered
      as an adjuvant to resection if margins are positive. Combined conservation
      resection and postoperative radiation should also be considered for situations
      where adequate wide excision alone would result in major cosmetic or functional
      deficits.

PMID- 9531367
TI  - Boron neutron-capture therapy (BNCT) for glioblastoma multiforme (GBM) using the
      epithermal neutron beam at the Brookhaven National Laboratory.
AB  - OBJECTIVE: Boron neutron-capture therapy (BNCT) is a binary form of radiation
      therapy based on the nuclear reactions that occur when boron (10B) is exposed to
      thermal neutrons. Preclinical studies have demonstrated the therapeutic efficacy
      of p-boronophenylalanine (BPA)-based BNCT. The objectives of the Phase I/II trial
      were to study the feasibility and safety of single-fraction BNCT in patients with
      GBM. MATERIALS AND METHODS: The trial design required (a) a BPA biodistribution
      study performed at the time of craniotomy; and (b) BNCT within approximately 4
      weeks of the biodistribution study. From September 1994 to July 1995, 10 patients
      were treated. For biodistribution, patients received a 2-hour intravenous (i.v.)
      infusion of BPA-fructose complex (BPA-F). Blood samples, taken during and after
      infusion, and multiple tissue samples collected during surgical debulking were
      analyzed for 10B concentration. For BNCT, all patients received a dose of 250 mg
      BPA/kg administered by a 2-hour i.v. infusion of BPA-F, followed by neutron beam
      irradiation at the Brookhaven Medical Research Reactor (BMRR). The average blood
      10B concentrations measured before and during treatment were used to calculate
      the time of reactor irradiation that would deliver the prescribed dose. RESULTS:
      10B concentrations in specimens of scalp and tumor were higher than in blood by
      factors of approximately 1.5 and approximately 3.5, respectively. The 10B
      concentration in the normal brain was < or = that in the blood; however, for
      purposes of estimating radiation doses to normal brain endothelium, it was always
      assumed to be equal to blood. BNCT doses are expressed as gray-equivalent (Gy
      Eq), which is the sum of the various physical dose components multiplied to
      appropriate biologic effectiveness factors. The dose to a 1-cm3 volume where the
      thermal flux reached a maximum was 10.6 +/- 0.3 Gy-Eq in 9 patients and 13.8 Gy
      Eq in 1 patient. The minimum dose in tumor ranged from 20 to 32.3 Gy-Eq. The
      minimum dose in the target volume (tumor plus 2 cm margin) ranged from 7.8 to
      16.2 Gy-Eq. Dose to scalp ranged from 10 to 16 Gy-Eq. All patients experienced in
      field alopecia. No CNS toxicity attributed to BNCT was observed. The median time
      to local disease progression following BNCT was 6 months (range 2.7 to 9.0). The
      median time to local disease progression was longer in patients who received a
      higher tumor dose. The median survival time from diagnosis was 13.5 months.
      CONCLUSION: It is feasible to safely deliver a single fraction of BPA-based BNCT.
      At the dose prescribed, the patients did not experience any morbidity. To further
      evaluate the therapeutic efficacy of BNCT, a dose-escalation study delivering a
      minimum target volume dose of 17 Gy-Eq is in progress.

PMID- 9531368
TI  - Direct injection of 90Y MoAbs into glioma tumor resection cavities leads to
      limited diffusion of the radioimmunoconjugates into normal brain parenchyma: a
      model to estimate absorbed radiation dose.
AB  - PURPOSE: Previously we have demonstrated that radioimmunoconjugates can be
      injected into glioma resection cavities to deliver a boost of radiation to the
      cavity edge with little toxicity to the normal brain. In the mathematical models
      we have previously published to assist in the development of this strategy we
      assumed that antibody remains associated with the cavity edge and no diffusion
      occurs. However, moderate diffusion might be beneficial while, if this were
      excessive, it would decrease the therapeutic index markedly. METHODS AND
      MATERIALS: Selected individuals with relapsed malignant glioma underwent further
      surgical debulking; 90Y MoAb radioimmunotherapy; and open biopsy to determine the
      extent to which the conjugate diffuses from the cavity edge. Samples from these
      patients were taken in radial tracts and the corrected activity in each sample
      was plotted against distance from the cavity wall to determine appropriate
      diffusion constants. RESULTS: Our data indicates that diffusion of
      radioimmunoconjugate from the edge of a glioma resection cavity appears to be an
      exponential process. The mean Ro for each patients data set ranged from 0.48-0.63
      (overall mean 0.6) cm. A dosimetric model was developed that translates these
      measurements into estimates of radiation dose. Applying the clinical data to this
      model indicates that, in each patient, the peak dose is delivered 0.16-0.18 cm
      below the cavity margin, and the mean dose at 2 cm deep is 5.3% (4.4-5.8%) of the
      peak. CONCLUSION: The model described can be used to translate diffusion
      constants measured by any method into estimates of absorbed radiation dose.
      Assuming similar diffusion kinetics, it can also be used to predict the dose
      deposited if alternative radionuclides are linked to MoAb, although the effect of
      dose rate should also be considered. In the future, it may be possible to
      manipulate diffusion by using either different antibodies or antibody fragments
      for intracavity radioimmunotherapy. Before this can be done, however, further
      data are needed and a noninvasive approach to measuring diffusion would clearly
      be optimal.

PMID- 9531369
TI  - Ependymoma: results, prognostic factors and treatment recommendations.
AB  - PURPOSE: To review the University of Florida experience in treating ependymomas,
      analyze prognostic factors, and provide treatment recommendations. METHODS AND
      MATERIALS: Forty-one patients with ependymoma and no metastases outside the
      central nervous system received postoperative radiotherapy with curative intent
      between 1966 and 1989. Ten patients had supratentorial lesions, 22 had
      infratentorial lesions, and 9 had spinal cord lesions. All patients had surgery
      (stereotactic biopsy, subtotal resection, or gross total resection). Most
      patients with high-grade lesions received radiotherapy to the craniospinal axis.
      Low-grade intracranial lesions received more limited treatment. Spinal cord
      lesions were treated using either partial spine or whole spine fields. RESULTS:
      Of 32 intracranial tumors, 21 recurred, all at the primary site; no spinal cord
      tumors recurred. Overall 10-year survival rates were 51% (absolute) and 46%
      (relapse-free); by tumor site: spinal cord, 100%; infratentorial, 45%;
      supratentorial, 20% (p = 0.002). On multivariate analysis, tumor site was the
      only factor that influenced absolute survival (p = 0.0004); other factors
      evaluated included grade, gender, age, duration of symptoms, resection extent,
      primary tumor dose, treatment field extent, surgery-to-radiotherapy interval, and
      days under radiotherapy treatment. CONCLUSIONS: Patients with supratentorial or
      infratentorial tumors receive irradiation, regardless of grade. Craniospinal-axis
      fields are used when spinal seeding is radiographically or pathologically
      evident. Spinal cord tumors are treated using localized fields to the primary
      site if not completely resected. Failure to control disease at the primary site
      remains the main impediment to cure.

PMID- 9531370
TI  - Factors determining outcome for breast-conserving irradiation with margin
      directed dose escalation to the tumor bed.
AB  - PURPOSE: A prospectively applied treatment policy for breast-conserving therapy
      used margin assessment as the exclusive guide to the intensity of therapy
      directed at the tumor-bearing quadrant. METHODS AND MATERIALS: From 1982-1994,
      there were 509 treated Stage I and II breast carcinomas with a median follow-up
      of 72 months. For operational purposes, tumor excision margins were prospectively
      defined as: > 5 mm, 2.1-5 mm, > 0 < or = 2 mm, and positive. If a margin was
      assessed as < or = 2 mm or indeterminate, and it was deemed cosmetically
      feasible, a reexcision of the tumor bed would be performed. All patients received
      whole breast irradiation to 50-50.4 Gy. The following scheme for tumor bed boost
      irradiation as a function of final margin status (FMS) was observed: (a) Minimal
      risk = no tumor found on reexcision, no boost performed; (b) low risk = FMS > 5
      mm, boost of 10 Gy; intermediate risk = FMS 2.1-5 mm, boost to 14 Gy; high risk =
      FMS < or = 2 mm or positive, boost to 20 Gy. Cases were analyzed for local
      failure (LF) with respect to histology (invasive ductal (IDC), IDC with
      associated DCIS (IDC/DCIS), invasive lobular (ILC)), age, tumor size, total
      excision volume, reexcision, total dose, tamoxifen therapy, and chemotherapy.
      RESULTS: There were 19 breast recurrences for a Kaplan-Meier local failure rate
      for all cases at 5 and 10 years of 2.7% and 7.1%, respectively. Local failure in
      the first 4 years of follow-up was rare, with a mean annual incidence rate of
      0.25% that rose to a mean of 1.1% in subsequent years. Univariate results of Cox
      proportional hazards regression survival models found positive FMS (p = 0.02),
      IDC/DCIS (p = 0.04) and age (0.0006) as significantly associated with local
      failure. In a multivariable model of FMS and IDC/DCIS, FMS retained significance
      (p = 0.01) but IDC/DCIS was borderline (p = 0.06). When FMS and age were included
      in a multivariable model, there was a significant interaction (p = 0.01) between
      the two variables. There was a significant increase in the relative risk of LF
      for age < or = 45 years (range 11.1-17.4), irrespective of FMS category. Although
      excellent overall control rates were achieved for patients > 45 years, for
      younger patients LF rates appeared to remain proportional to the relative
      closeness of the FMS, despite rigorous dose escalation. CONCLUSIONS: Graded tumor
      bed dose escalation in response to FMS results in an exceptionally low risk of
      "early" local recurrence within the first 5 years of follow-up. However, this
      strategy is unable to completely overcome the longer term adverse influence of
      young age and positive FMS.

PMID- 9531371
TI  - Local recurrence after breast-conserving therapy for invasive breast cancer: high
      incidence in young patients and association with poor survival.
AB  - PURPOSE: To study risk factors for local recurrence (LR) after breast-conserving
      therapy (BCT) for invasive breast cancer and, for patients with an LR, the mode
      of detection, location, treatment, influence of radiation therapy, and impact on
      survival. METHODS AND MATERIALS: 1360 patients (median age 52 years; range 24-88)
      with a total of 1393 pT1-2 N0-1 tumors treated with BCT between 1980-1994 were
      studied (median follow-up 52 months). The adequacy of radiation treatment of the
      patients developing LR was studied in a quality control study. The impact of LR
      on overall survival and distant metastasis was studied in a Cox regression model
      with LR as a time-dependent covariate. RESULTS: A total of 88 LR occurred with a
      5- and 10-year LR risk of 8 and 12%. Age was the only significant risk factor.
      Compared to patients > 65 years old, patients < 45 years old and patients 45-65
      years old had a relative risk (RR) of 4.09 and 2.41, respectively, of developing
      LR. Risk on LR was found to increase gradually with younger age. Radiation
      therapy was considered adequate and did not play a role in influencing the LR
      rate. Almost 65% of the LR were true or marginal recurrences. Of all LR, 80%
      appeared during the first 5 years and were detected with equal frequency by the
      patient herself, the physician, and annual mammography. LR was a major predictor
      for distant metastasis (RR: 4.90; 3.15-7.62) and death (RR: 4.29; 2.93-6.28).
      CONCLUSION: Young age is a major risk factor for LR and there is a significant
      gradual increase in LR with decreasing age. LR is associated with a higher risk
      of distant metastasis and death. Whether LR is the cause of or a marker for
      distant metastasis remains unresolved.

PMID- 9531372
TI  - Does delay in breast irradiation following conservative breast surgery in node
      negative breast cancer patients have an impact on risk of recurrence?
AB  - PURPOSE: This retrospective review was conducted to determine if delay in the
      start of radiotherapy after definitive breast surgery had any detrimental effect
      on local recurrence or disease-free survival in node-negative breast cancer
      patients. METHODS AND MATERIALS: A total of 568 patients with T1-T2, N0 breast
      cancer were treated with breast-conserving surgery and breast irradiation,
      without adjuvant systemic therapy between January 1, 1985 and December 31, 1992,
      at the London Regional Cancer Centre. Adjuvant breast irradiation consisted
      either of 50 Gy in 25 fractions or 40 Gy in 15 or 16 fractions, followed by a
      boost of 10 Gy or 12.5 Gy to the lumpectomy site. The time intervals from
      definitive breast surgery to breast irradiation used for analysis were 0-8 weeks
      (201 patients), > 8-12 weeks (235 patients), > 1216 weeks (91 patients), and > 16
      weeks (41 patients). The time intervals of 0-12 weeks (436 patients) and > 12
      weeks (132 patients) were also analyzed. Kaplan-Meier estimates of time to local
      recurrence and disease-free survival rates were calculated. The association
      between surgery-radiotherapy interval, age (< or = 40, > 40 years), tumor size (<
      or = 2, > 2cm), Scharf-Bloom-Richardson (SBR) grade, resection margins, lymphatic
      vessel invasion, extensive intraductal component, and local recurrence and
      disease-free survival were investigated using Cox regression techniques. RESULTS:
      Median follow-up was 63.5 months. Patients in all 4 time intervals were similar
      in terms of age and pathologic features. There was no statistically significant
      difference between the 4 groups in local recurrence or disease-free survival with
      surgery-radiotherapy interval (p = 0.189 and p = 0.413, respectively). The 5-year
      freedom from local relapse was 95.4%. The crude local recurrence rate was 6.9%
      (7.8% for 436 patients treated within 12 weeks (median follow-up 67 months) and
      3.8% for 132 patients treated > 12 weeks from surgery (median follow-up 52
      months). In a stepwise multivariable Cox regression model for disease-free
      survival, allowing for entry of known risk factors, tumour size (p < 0.001),
      grade (p < 0.001), and age (p = 0.048) entered the model, but the surgery
      radiotherapy interval did not enter the model. CONCLUSION: This retrospective
      study suggests that delay in start of breast irradiation beyond 12 and up to 16
      weeks does not increase the risk of recurrence in node-negative breast cancer
      patients. The certainty of these results are limited by the retrospective nature
      of this analysis and the lack of information concerning the late local failure
      rate.

PMID- 9531373
TI  - The importance of postoperative radiation therapy in multimodality management of
      locally advanced breast cancer: a phase II trial of neoadjuvant MVAC, surgery,
      and radiation.
AB  - PURPOSE: To determine the impact of postoperative radiation on locoregional
      relapse and overall survival rate in a multimodality protocol for locally
      advanced breast cancer (LABC). MATERIAL AND METHODS: Of the patients entered in
      the protocol, 55 were evaluable. Treatment consisted of: neoadjuvant MVAC
      (methotrexate, vinblastine, adriamycin, and cisplatin) until a maximum response
      had been achieved; modified radical mastectomy; 6 courses of postoperative
      adjuvant MVAC chemotherapy, and chest wall irradiation (CWXRT). Multivariate
      analysis of locoregional response and overall survival was done. RESULTS: Of the
      total, 42 patients received chest wall radiation; 28 of these also received
      radiation to regional lymph nodes. Chest wall doses ranged from 45 Gy to 50.4 Gy
      to the whole chest wall, with 31 patients receiving an additional chest-wall
      boost. The incidence of locoregional relapse with and without radiation was 7%
      vs. 31%, respectively (p = 0.026). An overall survival benefit was seen in those
      receiving radiation, with a mean overall survival of 50 months vs. 20 months, and
      a 3-year overall survival of 88% vs. 46% with and without radiation, respectively
      (p = 0.003). Multivariate analysis showed that overall survival was affected by
      the presence of pathological CR (p = .047), the number of pre-operative
      chemotherapy cycles (p = .036) and whether or not they received radiation (p =
      0.003). Neither the interval between surgery and radiation, technique of
      radiation, nor radiation modality significantly affected local control.
      CONCLUSION: The significant improvement in local regional control and overall
      survival with the addition of radiation suggests that radiation should be an
      integral part of multimodality management of locally advanced breast cancer.

PMID- 9531374
TI  - High-dose-rate intracavitary brachytherapy in the management of cervical and
      vaginal intraepithelial neoplasia.
AB  - PURPOSE: To assess the effectiveness of high-dose rate intracavitary
      brachytherapy (HDR-ICR) in patients with grade 3 cervical intraepithelial
      neoplasia (CIN-3) and grade 3 vaginal intraepithelial neoplasia (VAIN-3). METHODS
      AND MATERIALS: This was a retrospective analysis in 20 patients with CIN-3 (n =
      14) or VAIN-3 (n = 6), average age 61.9 years, managed with HDR-ICR at Kanagawa
      Cancer Center. Two patients with CIN-3 with microinvasive foci and 11 other
      patients with CIN-3 were treated with HDR-ICR for cervical lesions. Six patients
      with CIN-3 after hysterectomy received HDR-ICR for recurrent or residual VAIN-3
      lesions. One patient received radiation therapy for both CIN-3 and VAIN-3
      lesions. All these patients but one were postmenopausal. RESULTS: Seventeen
      patients were treated with HDR-ICR alone, and three with combined external
      radiation therapy. The dose was calculated at Point A located 2 cm superior to
      the external os and 2 cm lateral to the axis of the intrauterine tube for intact
      uterus. For lesions of the vaginal stump, the dose was calculated at a point 1 cm
      superior to the vaginal apex or 1 cm beyond vaginal mucosa. In the 14 patients
      treated for CIN-3 lesions, the mean total dose of HDR-ICR was 26.1 Gy (range 20
      30). Six patients received HDR-ICR for VAIN-3 lesions with mean dose of 23.3 Gy
      (range 15-30). At follow-up (mean 90.5 months; range 13-153), 14 patients were
      alive and 6 had died owing to nonmalignant intercurrent disease. No patient
      developed recurrent disease. Rectal bleeding occurred in three patients, but this
      symptom subsided spontaneously. Moderate and severe vaginal reactions were noted
      in two patients, in whom the treatment had included the entire vagina.
      CONCLUSIONS: HDR-ICR can be employed as the primary management strategy for
      postmenopausal women with CIN-3. In intraepithelial neoplasia involving the
      vaginal wall after hysterectomy, HDR-ICR should be considered as an alternative
      to total vaginectomy.

PMID- 9531375
TI  - Neoadjuvant chemotherapy followed by radiotherapy should not be a standard
      approach for locally advanced cervical cancer.
AB  - PURPOSE: To investigate the role of neoadjuvant chemotherapy followed by
      radiotherapy in locally advanced cervical cancer. METHODS AND MATERIALS: This
      study cites all known literature on the subject in the English language. Articles
      were selected for analysis by MEDLINE and CANCERLINE computer searches. In Phase
      II trials, the response rates of some selective series were analyzed. However,
      This article will specially emphasize the result of all Phase III randomized
      trials. RESULTS: Several investigators did obtain promising results from Phase II
      trials of neoadjuvant chemotherapy, mostly cisplatin-based combinations, followed
      by radiotherapy. However, most Phase III trials failed to demonstrate any benefit
      in terms of loco-regional relapse and/or survival by up-front chemotherapy.
      CONCLUSION: The role of neoadjuvant chemotherapy remains to be defined, and the
      search for more active new agents must be continued. The neoadjuvant setting is
      still experimental and could not be recommended as a standard treatment at the
      present.

PMID- 9531377
TI  - Radiotherapeutic management of osseous metastases: a survey of current patterns
      of care.
AB  - PURPOSE: Radiotherapy plays a major role in the management of painful osseous
      metastases. This survey was conducted to study the current approaches to this
      clinical problem in the radiotherapy community. METHODS AND MATERIALS: A
      questionnaire was sent to 2500 members of the American Society for Therapeutic
      Radiology and Oncology. It consisted of 30 multiple-choice questions regarding
      four hypothetical clinical scenarios likely to be encountered in daily practice.
      Questions related to the technique of choice [local field (LF) vs. hemibody
      radiotherapy (HBI)], the use of systemic radionuclides (SR), fractionation
      schemes, dose, the integration of modalities, and the follow-up of these
      patients. The analysis is based on 817 (33%) responses received regarding 3268
      cases. RESULTS: Local field is the most common form of therapy. Overall, LF was
      used, alone or in combination with other forms of therapy, in 54% and 74% of
      patients, respectively. LF was used more frequently in patients with breast
      cancer than in patients with prostate cancer (79% vs. 45%; p = 0.0001). Long
      fractionation schemes were used by 90% of physicians in 96% of cases. Short
      fractionation schemes were used by 7% of physicians in 4% of cases. This tendency
      was more pronounced in private practice than in the university or government/
      multidisciplinary settings (p = 0.008) and in physicians starting their practice
      before 1982 (p = 0.05). The most common schedule was 30 Gy in 10 fractions, used
      by 77% of physicians in 64% of cases. HBI was used, alone or in combination with
      other forms of therapy, in 1% and 2% of patients, respectively. It was used more
      frequently in patients with prostate cancer than in patients with breast cancer
      (1.2% vs. 0.1%, respectively; p < 0.0001). SR were used alone or in combination
      with local-field irradiation in 21% and 40% of cases, respectively. SR were used
      more frequently in patients with prostate cancer than in those with breast cancer
      (28% vs. 0.2%, respectively;p < 0.00001). The most common radionuclide in use is
      Sr-89 (99%) at a dose of 4 mCi (73%) or 10.8 mCi (26%). CONCLUSIONS: Although LF
      remains the mainstay of therapy, our results demonstrate the emergence of a new
      pattern of practice: LF to the painful site in combination with SR for clinically
      occult metastases. Despite an ongoing academic debate regarding fractionation
      schemes, the vast majority of American practitioners advocate long schedules.

PMID- 9531376
TI  - How successful is high-dose (> or = 60 Gy) reirradiation using mainly external
      beams in salvaging local failures of nasopharyngeal carcinoma?
AB  - PURPOSE: To evaluate the efficacy of high-dose (> or = 60 Gy) reirradiation using
      mainly external beams in salvaging local failures of nasopharyngeal carcinoma
      (NPC) after modern primary radical radiotherapy that delivered radical dose-to
      target volumes defined by CT scan. METHODS AND MATERIALS: Nine hundred and three
      patients with nondisseminated NPC whose primary radical radiotherapy was
      administered between 1984 and 1989 inclusive were studied. One hundred and
      seventy-six had local failures comprising 9 persistences and 167 recurrences. In
      10 patients the local failures were preceded or accompanied by (within 2 months)
      distant metastases, and these were given supportive treatment or palliative
      radiotherapy in low dose (< 60 Gy) if symptomatic. Most of the rest (123 of 166)
      were treated with either reirradiation to high dose (> or = 60 Gy) using mainly
      external photon beams (n = 103) or nasopharyngectomy with/without radical neck
      dissection with/without postoperative radiotherapy (n = 20). The remainder (n =
      43) received only palliative treatments because of poor general condition and/or
      patients' refusal of radical treatments. The primary radiotherapy was planned on
      the basis of target volumes defined by CT scan and given to a standard
      nasopharyngeal dose of 62.5 Gy/29 fractions/6 weeks. In the presence of
      parapharyngeal involvement, an additional boost of 20 Gy/10 fractions/2 weeks was
      given via a posterior oblique photon beam. If local residual tumors were
      diagnosed at 4-6 weeks after the completion of external radiotherapy, an
      additional boost of 24 Gy/3 fractions/15 days was given by intracavitary
      intubation. For the local failures given high-dose reirradiation, the target
      volume was defined by CT scan and treated by a two-field or a three-field photon
      arrangement with or without additional dose supplement by intracavitary
      intubation. Nasopharyngectomy was performed via the transcervico-mandibulo
      palatal approach or the maxillary swing approach. Radical neck dissection was
      only performed for the clinically evident nodal failures. RESULTS: With a median
      follow-up of 20 months (range 2.5-81 months) since the diagnosis of local
      failure, the actuarial 5-year overall survival, further relapse-free survival and
      free-from-local-tumor rates were 9.4, 11.5, and 18.7%, respectively, for the 123
      patients treated by either high-dose reirradiation (n = 103) or nasopharyngectomy
      (n = 20). Palliatively treated patients (n = 43) had a survival comparable to
      patients whose local failures were preceded or accompanied by distant metastasis
      (n = 10). Reirradiation to high dose (> or = 60 Gy) mainly by external photon
      beams achieved a 5-year overall survival of 7.6% and 5-year local control of
      15.2% with significant complications. Radiation-induced temporal lobe
      encephalopathy was radiologically evident in 21 patients (20.4%), and 13 of these
      21 patients were symptomatic. It could have been the cause of death in three
      patients who also suffered from uncontrolled local tumor. Significant morbidity
      was also associated with the other frequent radiation complications, including
      xerostomia, trismus, and deafness. Uni- and multivariate analyses indicated that
      brief initial disease-free interval between completion of primary radiotherapy
      and diagnosis of local failures and advanced recurrent T-stage and recurrent N
      stage were significant prognosticators predicting poor survival and/or further
      local failure after reirradiation. These patients were unlikely to benefit from
      the treatment. Nasopharyngectomy (+/- neck dissection +/- postoperative
      radiotherapy) was associated with earlier recurrent T-stages (mostly rT1 and rT2)
      and better survival and local control than reirradiation. However, restricting
      the comparison to rT1 and rT2 still demonstrated the superior results in favor of
      nasopharyngectomy, which could not be explained by the selection of less advanced
      lesions or patients with better performance status for surgery. (ABSTRACT
      TRUNCATED)

PMID- 9531378
TI  - External radiotherapy in macular degeneration: our technique, dosimetric
      calculation, and preliminary results.
AB  - PURPOSE: This study was performed to determine the toxicity and efficacy of
      external-beam radiotherapy in patients with age-related subfoveal
      neovascularization. METHODS AND MATERIALS: Between January 1996 and September
      1996, 25 patients with a mean age of 70.5 (60-84) years were enrolled. All
      patients underwent fluorescein angiographic evaluation and documentation of their
      neovascular disease prior to irradiation. A total of 25 patients were treated
      with a total dose of 12 Gy in 6 fractions over 8 days. We used a lens-sparing
      technique and patients were treated with a single lateral 6-MV photon beam. To
      assess the risk of radiation carcinogenesis after treatment of age-related
      subfoveal neovascularization, we estimated the effective dose for a standard
      patient on the basis of tissue-weighting factors as defined by the International
      Commission on Radiological Protection (ICRP). The calculations were made with TLD
      on a male randophantom. The lens dose was found to be 0.217 Gy per fraction.
      RESULTS: No significant acute morbidity was noted. Visual acuity was maintained
      or improved in 76% and 80% of treated patients at their 1- and 3-month follow-up
      examinations, respectively. On angiographic imaging, there was stabilization of
      subfoveal neovascular membranes in 23 patients (92%) at 3 months after
      irradiation. CONCLUSION: Our observations on these 25 patients in this study
      indicate that many patients will have improved or stable vision after
      radiotherapy treatment with low-dose irradiation.

PMID- 9531379
TI  - Cellular and molecular mechanisms of radiation inhibition of restenosis. Part I:
      role of the macrophage and platelet-derived growth factor.
AB  - PURPOSE: The major radiobiological issue in determining the rationale for the use
      of radiation to inhibit vascular restenosis is the identification of the target
      cell(s) and/or cytokine(s) responsible for neointimal hyperplasia and vascular
      remodeling. The central hypothesis of this report is that the macrophage/monocyte
      and PDGF are key elements in the process of neointimal hyperplasia seen following
      angioplasty, similar to their role in lesion formation and progression found in
      atherosclerotic thickening. Specific immunohistochemical and cytochemical stains
      were applied to a rat carotid model in a temporal series after balloon
      angioplasty to determine macrophage activity vs. smooth muscle cell
      proliferation, the latter being classically thought to be the cell responsible
      for restenosis. METHODS AND MATERIALS: Neointimal hyperplasia was created in an
      established rat carotid artery model by a balloon catheter technique. Immediately
      following injury, treatment groups received irradiation via high dose rate (HDR)
      brachytherapy, the 192Ir source being placed externally to the vessel. Radiation
      was delivered to a length of 2 cm of the injured vessel at doses of 5, 10, and 15
      Gy, and the animals were sacrificed at various time points following treatment
      (24 h to 6 months). Serial sections of tissue were stained immunohistochemically
      with the primary antibodies CD11b, mac-1, anti-PDGF, and alpha-smooth muscle
      actin. RESULTS: Immediately (24 h) postinjury, there is an apparent migration of
      macrophages seen in the adventitia; after 1 week, proliferation and migration of
      macrophages could be seen clearly within all the vessel layers, especially in the
      intima; by 3 weeks, when there was evidence of neointimal hyperplasia,
      macrophages could still be seen, mainly in the intima scattered among the smooth
      muscle cells and myofibroblasts, and to a lesser degree at 6 months. There was
      corresponding expression of PDGF, whenever and wherever there were zones of
      activation/neointimal hyperplasia. Alpha-smooth muscle actin staining identified
      the smooth muscle cells distinct from the macrophages, and these SMCs exhibited
      activation in the neointimal hyperplasia zones at all later time points.
      Furthermore, we showed that radiation significantly reduced the macrophage
      population, while the onset of neointimal hyperplasia was accompanied by a return
      of the macrophage population. CONCLUSION: Our results suggest that the activated
      adventitial macrophage/monocyte are the key cells responsible for initiating the
      arterial neointimal hyperplasia and vascular remodeling developing
      postangioplasty as they are in the initiation and perpetuation of atheromatous
      thickening. Irradiation delivered immediately postinjury is, therefore, highly
      effective, because the macrophage population is exquisitely radiosensitive.

PMID- 9531380
TI  - Tumour radiosensitization by high-oxygen-content gases: influence of the carbon
      dioxide content of the inspired gas on PO2, microcirculatory function and
      radiosensitivity.
AB  - PURPOSE: To measure the effects of breathing high-oxygen-content gases, with a
      CO2 fraction of between 0 and 10%, on tumour radiosensitivity, blood flow and
      oxygenation. METHODS AND MATERIALS: The murine sarcoma F was used, implanted
      subcutaneously (s.c.) in syngeneic CBA mice. We assessed the induced changes in
      tumour microregional blood flow and oxygenation using laser Doppler flowmetry,
      and pO2 histography, respectively. Radiation response was determined using an in
      vivo-in vitro clonogenic assay 18-20 h post treatment. RESULTS: The results show
      that the level of radiosensitization achieved is dependent on both the CO2
      content of the inspired gas and the duration of gas breathing. No
      radiosensitization was evident following inhalation of 90% O2 + 10% CO2. All
      other gases elicited radiosensitization; however, that achieved with 100% O2
      disappeared at the extended preirradiation breathing time of 45 min. At this
      time, radiosensitization was maintained for gases containing 1%, 2.5%, or 5% CO2.
      Changes in oxygenation, as measured by PO2 electrodes, did indicate improved
      oxygenation status during inhalation of the gases. However, the time-course and
      extent of the changes did not mirror accurately the changes in
      radiosensitization. All the gases with a CO2 content of 2.5% or greater induced a
      10-20% reduction in microregional blood flow, with no change evident following
      inhalation of 100% O2 or 99% O2 + 1% CO2. CONCLUSIONS: The data imply that the
      decreased radiosensitization seen at extended breathing times of oxygen is
      unrelated to blood flow changes. The fact that radiosensitization is seen with
      extended breathing times of gases containing 2.5% and 5% CO2, despite blood flow
      decreases, is indicative of other overriding physiological changes, perhaps
      related to oxygen utilisation. The studies overall indicate that, at least in the
      tumour investigated, radiosensitization is not affected if the CO2 content of the
      inspired gas is reduced from 5% to 2.5%, or even 1%. Further evaluation of the
      radiosensitizing effects of such gas mixtures is now warranted. In addition,
      comparison with recent studies of other tumour types, where carbogen has been
      shown to improve tumour blood flow, suggests that this may be a tumour-specific
      phenomenon. Based on these data, further effort is required to elucidate the
      physiological mechanisms that determine these blood flow changes.

PMID- 9531381
TI  - Interferons antagonize gamma-ray-induced depression of natural immunity.
AB  - PURPOSE: The aim of this study was to determine the inhibitory effects of in
      vitro radiation on the number and function of natural killer (NK) cells and to
      investigate the capability of interferons (IFNs) to restore the activity of NK,
      depressed by gamma-rays. METHODS AND MATERIALS: Mononuclear cells (MNC) were
      obtained from intact or in vitro irradiated (20 Gy) peripheral blood collected
      from healthy donors. Alternatively, MNC were irradiated (20 Gy) after separation
      from intact whole blood. The in vitro treatment of MNC with IFNs (alpha, beta, or
      gamma, 200 UI/ml) was performed at different times after or before radiation. The
      NK activity (4 h-51Cr release test), the percentage of CD16+/CD56+ cells and
      apoptosis (cytometric analysis), and binding (microscopic observation) were
      evaluated on Days 0, 1, 2, and 5 from gamma-ray exposure and IFNs treatment.
      RESULTS: The in vitro treatment of irradiated MNC with betaIFN after radiation
      completely reverses the inhibitory effects of gamma-rays on human NK activity.
      BetaIFN do not reduce the apoptosis induction by radiation and don't modify the
      number of CD16- or CD56-positive cells. The binding between irradiated effectors
      and tumor cells (K562) appears partially increased in betaIFN-treated MNC.
      CONCLUSIONS: The results of the present investigation suggest a possible role of
      betaIFN in reversing the detrimental effect of radiation on human natural
      immunity and provide a rational basis for in vivo use of betaIFN in cancer
      radiotherapy.

PMID- 9531382
TI  - Dose rate-dependent sparing of the gastrointestinal tract by fractionated total
      body irradiation in dogs given marrow autografts.
AB  - PURPOSE: We compared gastrointestinal toxicity of single vs. fractionated total
      body irradiation (TBI) administered at dose rates ranging from 0.021 to 0.75
      Gy/min in a canine model of marrow transplantation. METHODS AND MATERIALS: Dogs
      were given otherwise marrow-lethal single or fractionated TBI from dual 60Co
      sources at total doses ranging from 8-18 Gy and delivered at dose rates of 0.021,
      0.05, 0.10, 0.20, 0.40, and 0.75 Gy/min, respectively. They were protected from
      marrow death by infusion of previously stored autologous marrow cells and they
      were given intensive supportive care posttransplant. The study endpoint was 10
      day mortality from gastrointestinal toxicity. Logistic regression analyses were
      used to jointly evaluate the effects of dose rate, total dose, and delivery
      regimen on toxicity. RESULTS AND CONCLUSION: With increasing dose rates,
      mortality increased for either mode of delivery of TBI. With dose rates through
      0.10 Gy/min, mortality among dogs given single vs. fractionated TBI appeared
      comparable. Beginning at 0.20 Gy/min, fractionation appeared protective for the
      gastrointestinal tract. Results in dogs given TBI at 0.40 and 0.75 Gy/min,
      respectively, were comparable, and dose fractionation permitted the
      administration of considerably higher total doses of TBI than were possible after
      single doses, an increment that was on the order of 4.00 Gy. The data indicate
      that the impact of fractionating the total dose at high dose rates differs from
      the effect of fractionation at low dose rates.

PMID- 9531384
TI  - Multiple machine implementation of enhanced dynamic wedge.
AB  - PURPOSE: After acquiring 4 years of experience with Dynamic Wedge, a software
      driven one-dimensional (1D) compensation system, we implemented a new software
      version called Enhanced Dynamic Wedge (EDW). The EDW allows larger (30 cm) and
      asymmetric field sizes and additional angles for wedged fields. We implemented
      this software on four similar dual-energy accelerators that also possess upper
      and lower physical wedge sets. Our goal was to implement EDW with one common
      wedge factor (WF) table and one set of treatment-planning files. METHODS AND
      MATERIALS: We measured WFs with an ionization chamber and isodose profiles with
      both film and a diode array. We used a calculation scheme that requires only
      entry of the wedge angle and fixed jaw value. Filters for computerized treatment
      planning were configured for each wedge angle. We also examined to what degree
      the multileaf collimation (MLC) orientation, which is orthogonal to the EDW
      direction, was compromised for specific treatment sites. As a comparative test,
      we examined the dosimetric consistency for the 8 sets of physical wedges on the
      four machines. Finally, we updated our DW quality assurance program for EDW.
      RESULTS: The measured EDW WF was common for all four machines to within +/- 1.5%
      and the calculation scheme held to within 1.5%. The EDW isodoses were consistent
      among the machines as measured by film and diode array. The treatment-planning
      filters provided computed isodose profiles that were nearly identical to measured
      profiles. Regarding MLC orientation, we found that the collimator angle needed
      for EDW did not compromise isodose distributions, as apparent in measured
      isodoses and calculated dose-volume histograms. The consistency of the physical
      wedges did not fare as well. Two of the lower wedge sets had Wfs and profiles
      different (> 3%) from the other wedge sets. CONCLUSIONS: We have successfully
      implemented EDW on four machines using only one WF table and one set of treatment
      planning filters. The EDW provides for improved treatment techniques for
      particular sites due to the large field sizes and additional angles available.
      Daily treatment efficiency has increased because of the remote capability
      provided by EDW.

PMID- 9531383
TI  - Electronic portal imaging with on-line correction of setup error in thoracic
      irradiation: clinical evaluation.
AB  - PURPOSE: To analyze setup errors and the feasibility of their on-line correction
      using electronic portal imaging in the irradiation of lung tumors. METHODS AND
      MATERIALS: Sixteen patients with lung cancer were irradiated through opposed
      anteroposterior fields. Localization images of anteroposterior fields were
      recorded with an electronic portal imaging device (EPID). Using an in-house
      developed algorithm for on-line comparison of portal images setup errors were
      measured and a correction of table position was performed with a remote couch
      control prior to treatment. In addition, residual errors were measured on the
      EPID verification image. Global and individual mean and standard deviation of
      setup errors were calculated and compared. The feasibility of the procedure was
      assessed measuring intra- and interobserver variability, influence of organ
      movement, reproducibility of error measurement, the extra time fraction needed
      for measuring and adjusting and the fraction of dose needed for imaging. RESULTS:
      In two setups the procedure could not be finished normally due to problems
      inherent to the procedure. The reproducibility, intraobserver variability, and
      influence of organ movements were each described by a distribution with a mean
      value less than or equal to 1 mm and a standard deviation (SD) of less than 1.5
      mm. The interobserver variability showed to be a little bit larger (mean: 0.3 mm,
      SD: 1.7 mm). The mean time to perform the irradiation of the anteroposterior
      field was 4 +/- 1 min. The mean time for the measurement and correction procedure
      approximated 2.5 min. The mean extra time fraction was 65 +/- 24% (1 SD) with
      more than half of this coming from the error measurement. The dose needed for
      generation of EPID images was 5.9 +/- 1.4% of total treatment dose. The mean and
      SD of setup errors were, respectively, 0.1 and 4.5 mm for longitudinal and -2.0
      and 5.7 mm for transversal errors. Of 196 measured translational errors 120 (61%)
      exceeded the adjustment criteria. For individual patients systematic and random
      setup errors can be as high as, respectively, 15.8 and 7.5 mm. Mean residual
      error and SD were for longitudinal direction 0.08 and 1.2 mm and for transversal
      direction -0.9 and 1.0 mm (pooled data). For individuals, the mean residual
      errors were smaller than 1 mm, with a typical SD per patient of less than 2 mm.
      CONCLUSION: Setup errors in thoracic radiation therapy are clinically important.
      On-line correction can be performed accurately with an objective measurement
      tool, although this prolongs the irradiation procedure for one field with 65%.

PMID- 9531385
TI  - Calibration of a mosfet detection system for 6-MV in vivo dosimetry.
AB  - PURPOSE: Metal oxide semiconductor field-effect transistor (MOSFET) detectors
      were calibrated to perform in vivo dosimetry during 6-MV treatments, both in
      normal setup and total body irradiation (TBI) conditions. METHODS AND MATERIALS:
      MOSFET water-equivalent depth, dependence of the calibration factors (CFs) on the
      field sizes, MOSFET orientation, bias supply, accumulated dose, incidence angle,
      temperature, and spoiler-skin distance in TBI setup were investigated. MOSFET
      reproducibility was verified. The correlation between the water-equivalent
      midplane depth and the ratio of the exit MOSFET readout divided by the entrance
      MOSFET readout was studied. MOSFET midplane dosimetry in TBI setup was compared
      with thermoluminescent dosimetry in an anthropomorphic phantom. By using
      ionization chamber measurements, the TBI midplane dosimetry was also verified in
      the presence of cork as a lung substitute. RESULTS: The water-equivalent depth of
      the MOSFET is about 0.8 mm or 1.8 mm, depending on which sensor side faces the
      beam. The field size also affects this quantity; Monte Carlo simulations allow
      driving this behavior by changes in the contaminating electron mean energy. The
      CFs vary linearly as a function of the square field side, for fields ranging from
      5 x 5 to 30 x 30 cm2. In TBI setup, varying the spoiler-skin distance between 5
      mm and 10 cm affects the CFs within 5%. The MOSFET reproducibility is about 3% (2
      SD) for the doses normally delivered to the patients. The effect of the
      accumulated dose on the sensor response is negligible. For beam incidence ranging
      from 0 degrees to 90 degrees, the MOSFET response varies within 7%. No monotonic
      correlation between the sensor response and the temperature is apparent. Good
      correlation between the water-equivalent midplane depth and the ratio of the exit
      MOSFET readout divided by the entrance MOSFET readout was found (the correlation
      coefficient is about 1). The MOSFET midplane dosimetry relevant to the
      anthropomorphic phantom irradiation is in agreement with TLD dosimetry within 5%.
      Ionization chamber and MOSFET midplane dosimetry in inhomogeneous phantoms are in
      agreement within 2%. CONCLUSION: MOSFET characteristics are suitable for the in
      vivo dosimetry relevant to 6-MV treatments, both in normal and TBI setup. The TBI
      midplane dosimetry using MOSFETs is valid also in the presence of the lung, which
      is the most critical organ, and allows verifying that calculation of the lung
      attenuator thicknesses based only on the density is not correct. Our MOSFET
      dosimetry system can be used also to determine the surface dose by using the
      water-equivalent depth and extrapolation methods. This procedure depends on the
      field size used.

PMID- 9531386
TI  - Fetal dose evaluation during breast cancer radiotherapy.
AB  - PURPOSE: The aim of the work was to estimate the radiation dose delivered to the
      fetus in a pregnant patient irradiated for breast cancer. METHODS AND MATERIALS:
      A 45-year woman was treated for left breast cancer using a 6 MV photon beam with
      two isocentric opposing tangential unwedged fields. Daily dose was 2.3 Gy at 95%
      isodose line given by two fields/day, 5 days/week. A total dose of 46 Gy was
      given in 20 fractions over a 4-week period. Pregnancy confirmed during the second
      therapeutic week. Treatment lasted between the second and sixth gestation week.
      Radiation dose to fetus was estimated from in vivo and phantom measurements using
      thermoluminescence dosimeters and an ionization chamber. In vivo measurements
      were performed by inserting either a catheter with TL dosimeters or ionization
      chamber into the patient's rectum. Phantom measurements were performed by
      simulating the treatment conditions on an anthropomorphic phantom. RESULTS: TLD
      measurements (in vivo and phantom) revealed fetal dose to be 0.085% of the tumor
      dose, corresponding to a cumulative fetal dose of 3.9 cGy for the entire
      treatment of 46 Gy. Chamber measurements (in vivo and phantom) revealed a fetal
      dose less than the TLD result: 0.079 and 0.083% of the tumor dose corresponding
      to cumulative fetal dose of 3.6 cGy and 3.8 cGy for in vivo and phantom
      measurement, respectively. CONCLUSIONS: It was concluded that the cumulative dose
      delivered to the unshielded fetus was 3.9 cGy for a 46 Gy total tumor dose. The
      estimated fetal dose is low compared to the total tumor dose given due to the
      early stage of pregnancy, the large distance between fundus-radiation field, and
      the fact that no wedges and/or lead blocks were used. No deterministic biological
      effects of radiation on the live-born embryo are expected. The lifetime risk for
      radiation-induced fatal cancer is higher than the normal incidence, but is
      considered as inconsequential.

PMID- 9531387
TI  - A survey of physics and dosimetry practice of permanent prostate brachytherapy in
      the United States.
AB  - PURPOSE: To obtain data with regard to current physics and dosimetry practice in
      transperineal interstitial permanent prostate brachytherapy (TIPPB) in the U.S.
      by conducting a survey of institutions performing this procedure with the
      greatest frequency. METHODS AND MATERIALS: Seventy brachytherapists with the
      greatest volume of TIPPB cases in 1995 in the U.S. were surveyed. The four-page
      comprehensive questionnaire included questions on both clinical and physics and
      dosimetry practice. Individuals not responding initially were sent additional
      mailings and telephoned. Physics and dosimetry practice summary statistics are
      reported. Clinical practice data is reported separately. RESULTS: Thirty-five
      (50%) surveys were returned. Participants included 29 (83%) from the private
      sector and 6 (17%) from academic programs. Among responding clinicians, 125I
      (89%) is used with greater frequency than 103Pd (83%). Many use both (71%). Most
      brachytherapists perform preplans (86%), predominately employing ultrasound
      imaging (85%). Commercial treatment planning systems are used more frequently
      (75%) than in-house systems (25%). Preplans take 2.5 h (avg.) to perform and are
      most commonly performed by a physicist (69%). A wide range of apparent activities
      (mCi) is used for both 125I (0.16-1.00, avg. 0.41) and 103Pd (0.50-1.90, avg.
      1.32). Of those assaying sources (71%), the range in number assayed (1 to all)
      and maximum accepted difference from vendor stated activity (2-20%) varies
      greatly. Most respondents feel that the manufacturers criteria for source
      activity are sufficiently stringent (88%); however, some report that vendors do
      not always meet their criteria (44%). Most postimplant dosimetry imaging occurs
      on day 1 (41%) and consists of conventional x-rays (83%), CT (63%), or both
      (46%). Postimplant dosimetry is usually performed by a physicist (72%), taking 2
      h (avg.) to complete. Calculational formalisms and parameters vary substantially.
      At the time of the survey, few institutions have adopted AAPM TG-43
      recommendations (21%). Only half (50%) of those not using TG-43 indicated an
      intent to do so in the future. Calculated doses at 1 cm from a single 1 mCi
      apparent activity source permanently implanted varied significantly. For 125I,
      doses calculated ranged from 13.08-40.00 Gy and for 103Pd, from 3.10 to 8.70 Gy.
      CONCLUSION: While several areas of current physics and dosimetry practice are
      consistent among institutions, treatment planning and dose calculation techniques
      vary considerably. These data demonstrate a relative lack of consensus with
      regard to these practices. Furthermore, the wide variety of calculational
      techniques and benchmark data lead to calculated doses which vary by clinically
      significant amounts. It is apparent that the lack of standardization with regard
      to treatment planning and dose calculation practice in TIPPB must be addressed
      prior to performing any meaningful comparison of clinical results between
      institutions.

PMID- 9531388
TI  - Regarding, Miralbell, Bleher, Huguenin et al., IJROBP 37:523-529; 1997.

PMID- 9531389
TI  - Regarding, Vicini, Chen, Fraile et al., IJROBP 38:301-310; 1997.

PMID- 9531390
TI  - Regarding, Willins, and Wallner, IJROBP 39:347-353; 1997.

PMID- 9531391
TI  - Regarding, Wu, Chua, Sham et al, IJROBP 37(4):913-920; 1997.

PMID- 9531392
TI  - The challenge of growth: the fourth dimension of pediatric care.

PMID- 9531394
TI  - The influence of transphyseal drilling and tendon grafting on bone growth: an
      experimental study in the rabbit.
AB  - The undulating area of the distal femoral physis has been measured in New Zealand
      White rabbits, by using an image analyzer in histologic sections, and correlated
      to radiographic measurements. The relative size of a physeal drill injury
      necessary to cause growth disturbance has been found to be 7-9%. A transphyseally
      placed tendon, even as a free graft, prevented solid bone-bridge formation in the
      drill hole and growth disturbance. The results are of possible clinical
      significance.

PMID- 9531393
TI  - Response of physeal cartilage to low-level compression and tension in organ
      culture.
AB  - The clinical response of growth plate to exogenous forces is well recognized,
      although the organ-level mechanisms are poorly understood. Physeal cartilage from
      5- to 7-day-old bovine distal radii was subjected to 245 N of tension or 245 N of
      compression (0.012 MPa) in organ culture over a 24-h period. Eleven specimens
      (six tension, five compression) were assayed for cellular proliferation with
      tritiated thymidine. Eighteen specimens (12 tension, six compression) were
      assayed for synthetic activity with radioactive sulfate. Media were assayed for
      prostaglandin production. Tension increased whereas compression decreased
      synthetic activity and prostaglandin production by physeal cartilage in explant
      culture over a 24-h period. There was no significant change in thymidine uptake.
      Physeal cartilage can respond to both tension and compression and, in the short
      term, appears to alter synthetic activity without changing the rate of cell
      proliferation. This study system allows local sampling and manipulation of the
      physeal organ environment and may lead to ways of approaching growth-plate
      pathologies in vivo.

PMID- 9531395
TI  - Treatment of growth arrest by transfer of cultured chondrocytes into physeal
      defects.
AB  - Chondrocytes were cultured from cartilage harvested from the iliac apophysis and
      knee joints of New Zealand White (NZW) rabbits. An experimental model for growth
      arrest was created by excising the medial half of the proximal growth plate of
      the tibia of 6-week-old NZW rabbits. The cultured chondrocytes were embedded in
      agarose and transferred into the growth-plate defect after excision of the
      physis. Transfer also was performed after excision of the bony bridge in
      established growth arrest. In both cases, growth arrest with angular deformation
      of the tibia was prevented. Histologic studies confirmed the viability of the
      chondrocytes in the new host physis.

PMID- 9531396
TI  - A new look at the sequential development of elbow-ossification centers in
      children.
AB  - The pattern and sequence of ossification of the six secondary ossification
      centers around the elbow in the child were mainly derived from studies done >30
      years ago. This series reexamined the sequence and pattern based on a cross
      sectional study of the elbow radiographs of 1,577 Chinese children with elbow
      injuries; age range, from newborn to 17 years. The ratio of girls to boys was
      1:2. Each child had a radiograph of the normal and the injured elbow giving a
      total of 3,154 radiographs. A percentile chart of ossification was constructed
      for each of the ossification centers in both sexes for easy reference. No
      differences in the timing and ossification pattern were found between the right
      and left elbow or between the normal and injured elbow in this study. The
      sequence of ossification in both boys and girls was found to be the same (i.e.,
      the capitulum first, followed by the radial head, medial epicondyle, olecranon,
      trochlea, and last, the lateral epicondyle). The ages at which 50% of the girls
      were found to have positive radiologic ossification for each of these centers
      were ages 1, 5, 5, 9, 9, and 10 years, respectively. In boys, with the exception
      of the capitulum, an average delay of 2 years was found in each of the
      ossification centers, although the sequence remained similar.

PMID- 9531397
TI  - Age of closure of the neurocentral cartilage in the thoracic spine.
AB  - We reviewed magnetic resonance images (MRIs) of 91 patients to estimate the
      chronologic age of closure of the neurocentral cartilage in the thoracic spine.
      The neurocentral cartilage on MRI appeared low signal in both T1- and T2-weighted
      images. It was thick and clearly identified in younger patients but was thin and
      vague in older patients. The neurocentral cartilage closed at 11-16 years in
      female patients and at 12-16 years in male patients.

PMID- 9531398
TI  - Role of the ossification groove of Ranvier in normal and pathologic bone growth:
      a review.
AB  - According to Ranvier (1889), cells in the ossification groove originate in
      cartilage and differentiate to osteoblasts. He was supported by others until some
      authors stated after 1950 that the growth plate grows in width by apposition of
      cells from the groove. The apposition theory is still accepted in several
      textbooks. Our experiments with roentgen ray injury showed (1950) migration of
      cells toward the ossification groove in the germinal layer of the growth plate, a
      phenomenon not described by others. It was verified in normal bones with 35S
      (1967) and with vital staining (1993). In situ hybridization of bones in rabbits
      showed (1993) that cells in the groove and adjacent periosteum contain type II
      collagen messenger RNA (mRNA) characteristic of cartilage, a finding in
      accordance with Ranvier's views. The behavior of cells in the ossification groove
      plays a decisive role in the pathogenesis of several diseases of the growing
      skeleton.

PMID- 9531399
TI  - Acute correction and distraction osteogenesis for the malaligned and shortened
      lower extremity.
AB  - In limbs with combined shortening with angulation or malrotation, deformity may
      be quickly or slowly corrected before lengthening with external fixation. We
      examined a series of 35 patients with 40 limbs that underwent acute deformity
      correction and subsequent gradual lengthening. The average deformity corrected
      was 19 degrees, with subsequent average lengthening of 4.1 cm. Good radiographic
      callus formation was noted in 34 of the 40 segments studied. The magnitude of
      deformity correction had no effect on the quality of lengthened bone, incidence
      of complications, or the healing index. Skeletally mature segments had
      statistically significant decreased bone formation (p = 0.001), increased
      prevalence of callus complications (p = 0.001), and a higher healing index (p =
      0.003). Based on this experience, it is our conclusion that immediate correction
      and lengthening is suitable in children and adolescents who have malaligned and
      shortened lower extremities. Because of poorer results in older patients, we
      believe that other techniques should be considered in adults.

PMID- 9531400
TI  - Kinematic and kinetic asymmetry in patients with leg-length discrepancy.
AB  - The symmetry index (SI), as one of methods to evaluate gait pattern in patients
      with leg-length discrepancy (LLD), helps to estimate the acceptable range of
      inequality and to determine symmetry in the kinematic and kinetic data before and
      after a heel lift, although this parameter has a large standard deviation that
      undermines its accuracy. Thirty patients with LLD were studied by a motion
      analysis system and a force plate. Joint motion of the lower extremity in the
      sagittal plane, back movement in the coronal plane, and three-dimensional ground
      reaction forces (GRFs) were registered. From a linear-regression analysis, a mean
      value of inequality of 2.33 cm (range, 2.12-2.54) was found to correspond to an
      acceptable gait symmetry. After a heel lift, the SI of the pelvic tilt at
      midstance and of the vertical GRF at initial contact increases significantly, but
      the SI of the medial GRF at terminal stance decreases. Patients with an
      inequality of a mean value of 0.51 cm determined by palpating bilaterally the top
      of the iliac crest (the TIC1 subgroup) showed a lesser value of the SI of the
      center of pressure in the forward direction during stance compared with the group
      with a mean value of inequality of 1.39 cm (the TIC2 subgroup). As a result of
      our findings, we conclude that the effect of the amount of correction by a heel
      lift on gait symmetry is unpredictable.

PMID- 9531401
TI  - Growth arrest resulting from unicameral bone cyst.
AB  - Growth arrest complicating unicameral bone cyst of the proximal humerus is
      reported in five patients. These patients represented 10% of 51 consecutive
      patients treated by the senior author at our hospital from 1988 through 1995. The
      youngest patient at first clinical presentation was aged 6 years, and the oldest
      was 14 years 9 months. The follow-up ranged from 35 to 69 months (average, 57.2).
      The youngest patient at final follow-up was 9 years 1 month, and the oldest was
      20 years 5 months. Pathologic fracture was the common clinical presentation in
      all patients. Growth arrest was diagnosed by limb-length discrepancies, as well
      as radiographic evidence of premature closure of the physis and deformity of the
      upper humerus. Treatment was either aspiration of the cyst and local injection of
      corticosteroids or curettage and bone grafting. Growth arrest was documented,
      both clinically and radiographically, before the surgery in the two cases treated
      by curettage and grafting. The origin of growth arrest resulting from unicameral
      bone cyst remains uncertain. Direct iatrogenic damage to the physis was not a
      likely cause of growth arrest in this series. Growth arrest as a complication of
      unicameral bone cyst of the proximal humerus is more common than is generally
      appreciated (10%).

PMID- 9531402
TI  - Ollier's disease: varus angulation at the lower femur and its management.
AB  - Attention is drawn to the high incidence of varus angulation in the lower femur
      in Ollier's disease; eight of a total of 14 patients with this condition have
      this deformity. There may be retardation or arrest of the medial portion of the
      lower femoral growth plate. One case demonstrates a bone bridge, a condition not
      previously described in Ollier's disease. The limb-length inequality and varus
      angulation require concurrent management by a variety of techniques, which are
      described. Three of the eight patients have reached skeletal maturity; the
      remainder provide useful information on the condition and are a stimulus for
      discussion of future management.

PMID- 9531403
TI  - Aneurysmal bone cysts of the spine: excision and stabilization.
AB  - The treatment of aneurysmal bone cysts (ABCs) of the spine remains controversial
      in the literature. Treatment options have included radiation, curettage and bone
      graft, extirpation, and various combinations of these. Conspicuously missing in
      previously published articles and texts are guidelines for dealing with the
      instability and deformity that often accompany ABCs of the spine. The index case
      in this report highlights the potentially devastating effects of treating the
      tumor in isolation without addressing the concomitant deformity and instability.
      The status of the structural integrity of the spine must be assessed before
      initiating treatment. If instability or deformity or both are already present or
      if the amount of osseous tissue to be resected may render the spine unstable,
      then instrumentation and fusion should be performed at the time of surgical
      resection or before other forms of therapy. We present three cases of ABCs of the
      spine in which the tumor itself was treated with surgical extirpation and the
      associated deformity and instability were treated with spinal instrumentation and
      long fusions.

PMID- 9531404
TI  - Sternocleidomastoid pseudotumor of infants and congenital muscular torticollis:
      fine-structure research.
AB  - Fifty cases, 16 with sternocleidomastoid pseudotumor of infants (SCMPOI) and 34
      with congenital muscular torticollis (CMT), were investigated by light and
      electron microscopy. The ultrastructure of the pseudotumor revealed that there
      were myoblasts, fibroblasts, myofibroblasts, and mesenchyme-like cells, which
      consisted of fibrous tissue and were regarded as fibroblasts only in the
      literature. The myoblasts showed the various stages of differentiation and
      degeneration. For those cases without mass, the collagen fibrils and fibrocytes
      were often arranged in tight parallel bundles in which some muscles showed normal
      structure and some with decreased myofibrillae. The mesenchyme-like cells and
      myoblasts found in the pseudotumor may be the key point to its pathologic
      characteristics.

PMID- 9531405
TI  - Torticollis and hip dislocation.
AB  - Reports in the literature suggest that there is an association between two
      childhood disorders: torticollis, an easily recognized clinical deformity, and
      developmental dislocation or dysplasia of the hip, an occult disorder. The
      identification of the obvious disease, torticollis, may prompt a search for the
      occult disease, developmental dislocation of the hip. If the association of these
      two disorders is common, it may be justified to expend resources to diagnose the
      occult disorder in all cases in which the more obviously noticed disorder is
      recognized. The reported association varies between 2 and 29%. We retrospectively
      reviewed 70 patients with the diagnosis of congenital muscular torticollis to
      determine the incidence of hip dislocation or subluxation in these patients.
      Fifty-four patients had radiographs of their hips. Forty-one patients were
      available for follow-up at an average of age 3+4 years. Six patients were noted
      to have hip subluxation or dislocation, all at presentation. Of these, four had
      been referred for diagnosed hip disease, whereas two were referred for
      torticollis, and the hip disease was then diagnosed by the pediatric
      orthopaedist. No patient had abnormal radiographs or physical findings at follow
      up. We conclude that the rate of hip disease in those with torticollis is
      approximately 8% and is lower than the 20% often quoted.

PMID- 9531406
TI  - Trunk distortion in adolescent idiopathic scoliosis.
AB  - Trunk images of children with scoliosis were examined to determine features that
      contribute to the impression of trunk distortion. Twenty subjects with spinal
      deformity ranging from none to severe were photographed in a relaxed standing
      position. Seven blinded evaluators subjectively scored their impressions of the
      trunk appearance, shoulder-height difference, shoulder-angle asymmetry,
      decompensation, scapula asymmetry, waist crease, waist asymmetry, and pelvic
      asymmetry. Regression analysis was used with the latter seven features to predict
      overall impression. The seven measures of the deformity predicted 85% of the
      overall impression of trunk distortion; scapular asymmetry was the best
      predictor. Trunk deformity is the most obvious effect of scoliosis to the
      patients. Objective approaches to the assessment of this important but difficult
      to-quantify aspect of idiopathic scoliosis are available and should be used to
      evaluate treatment outcomes.

PMID- 9531407
TI  - Segmental spinal dysgenesis: a report of three cases.
AB  - Segmental spinal dysgenesis is an uncommon congenital spinal defect characterized
      by localized segmental agenesis of the upper lumbar or thoracolumbar spine. Bony
      defects include significant focal canal stenosis, hypoplastic or absent
      vertebrae, subluxation of the spinal column, and instability. The distal bony
      architecture is usually normal but may be bifid. There is significant narrowing
      of the thecal sac and absence of adjacent nerve roots at the level of the lesion.
      Distal neurologic deficits are variable in severity, the prevalence of neurogenic
      bladder is high, and associated anomalies are common. Progressive kyphosis is
      inevitable. The cause is unknown, but an association with maternal diabetes and
      with various medications and toxins has been noted. Other authors suggested a
      relation to an aberrant segmental vascular supply. Treatment should be directed
      at the establishment and maintenance of spinal stability and arrest of the
      progressive kyphosis. It should consist of early anterior and posterior
      arthrodesis, with or without anterior decompression of the cord. Accurate
      visualization of this unusual deformity is difficult with conventional
      radiographic techniques. Three-dimensional computerized tomographic
      reconstruction can therefore be invaluable in preoperative planning. We report
      three cases of segmental spinal dysgenesis, all of which have been uniquely
      detailed by striking three-dimensional imaging studies.

PMID- 9531408
TI  - A comparison of patients with different types of syndactyly.
AB  - We performed a retrospective review of finger syndactyly releases at Shriners
      Hospital for Children, Houston Unit, between January 1983 and January 1993. This
      study was performed in an attempt to compare the long-term postoperative function
      in patients after release of syndactyly resulting from Poland's syndrome with
      that in patients with idiopathic forms of syndactyly. Only patients with one
      involved hand were included in this study. The contralateral hand was used as a
      control. Twenty-seven patients with only one hand involved underwent syndactyly
      release during this period. Of these, 13 patients who underwent a total of 30
      syndactyly releases were available for evaluation. For each patient, the type of
      syndactyly was determined. Each patient was subjected to a detailed physical
      examination and participated in occupational-therapy modalities. We noted
      statistically significant differences in function between operated-on and control
      hands in the Poland's group, whereas operated-on hands affected with idiopathic
      forms of syndactyly did not demonstrate significantly different function compared
      with contralateral controls. These data suggest that functional deficits in hands
      affected by Poland's syndrome are attributable to more than the syndactyly alone.
      Hands affected by idiopathic forms of syndactyly are likely to have little
      postoperative functional deficit.

PMID- 9531409
TI  - Trigger finger in children.
AB  - Trigger finger in children is a rare condition. Thirty-three patients with 45
      trigger fingers (40 thumbs and five other fingers) were reviewed. As no case was
      detected at birth, the condition was suggested to be developmental. Surgi cal
      release was performed in 31 cases, with satisfactory results in all cases. Ten of
      31 cases were older than 3 years (range, 3-5 years). The age of the patient when
      the operation was indicated could be between 1 and 5 years.

PMID- 9531410
TI  - Chondrolysis of the hip after transfer of the greater trochanter.
AB  - Transfer of the greater trochanter is a surgical technique that is used for
      overgrowth of the greater trochanter arising from disturbance of the growth plate
      of the proximal femur. Few complications have been described, and to our
      knowledge, necrosis of the cartilage has not been reported. Herein we describe
      four cases of chondrolysis in three patients who underwent this surgical
      procedure. In our view, immobilization with plaster associated with the increased
      pressure produced by the descent of the gluteal attachment may have contributed
      to the development of chondrolysis.

PMID- 9531411
TI  - Retrospective review at skeletal maturity of the factors affecting the efficacy
      of Salter's innominate osteotomy in congenital dislocated, subluxed, and
      dysplastic hips.
AB  - This study reviewed at skeletal maturity 180 congenitally dislocated, subluxed,
      and dysplastic hips in 122 patients treated by the same surgeon by using Salter's
      innominate osteotomy (IO). The mean follow-up was 12 years. The sex of the
      patient, the laterality and height of the dislocation, the preoperative
      acetabular angle, the amount of femoral antetorsion, or the development of
      postoperative complications (except avascular necrosis of the femoral head), or a
      combination of these were not found to have a significant influence on the
      result. However, those patients who had a previous unsuccessful treatment of the
      hip, who developed pre- or postoperative avascular necrosis, who were unable to
      be restored by the osteotomy to a normal acetabular angle, or who required an
      open reduction of the hip joint (or who had a combination of these) were more
      likely to have an abnormal result. An important finding was that patients who
      underwent IO before age 4 years were the most likely candidates to receive a very
      satisfactory result.

PMID- 9531412
TI  - Pemberton osteotomy for the treatment of developmental dysplasia of the hip in
      older children.
AB  - A retrospective analysis was done of the results of the Pemberton osteotomy for
      the treatment of developmental dysplasia of the hip in 16 hips of 14 children
      older than 7 years. The average age of the patients at the time of surgery was
      11+6 years and the average follow-up was 4+10 years. Eleven hips required one or
      more surgical procedures concomitant with the Pemberton osteotomy to achieve a
      concentric and congruous reduction of the hip joint. None of the hips developed
      avascular necrosis of the acetabular fragment. The center-edge angle improved
      from a preoperative average of 1 degree to an average of 30 degrees at the most
      recent follow-up. Correction of acetabular dysplasia was noted in 14 of the 16
      hips, as demonstrated by the improvement in the acetabular index, the center-edge
      angle, and the Severin class. We believe that the Pemberton osteotomy can be a
      safe and effective procedure for the treatment of developmental dysplasia of the
      hip in the older child.

PMID- 9531414
TI  - Increasing prevalence of Kingella kingae in osteoarticular infections in young
      children.
AB  - Sixty children younger than 3 years with culture-positive hematogenous septic
      arthritis and acute/subacute osteomyelitis treated between 1990 and 1995 were
      reviewed to identify the infecting organism. Gram-positive bacteria were
      identified in 47 (78.3%) patients, and gram-negative organisms were identified in
      13 (21.7%) patients. Haemophilus influenzae was cultured in none of the cases of
      septic arthritis and in only one (1.6%) case of acute osteomyelitis. Kingella
      kingae was cultured in 10 (16.7%) cases, with all of these patients between the
      ages of 10.5 and 23.5 months. Routine immunization of infants against H.
      influenzae has caused a change in the historically reported bacteria of bone and
      joint infections in children younger than 3 years. Haemophilus influenzae has
      lost its predominance as the most commonly identified gram-negative pathogen, and
      in this study, has been replaced by K. kingae.

PMID- 9531413
TI  - Intraoperative sonography-guided removal of radiolucent foreign bodies.
AB  - This article reports our use of intraoperative sonography to guide in real time,
      the removal of radiolucent foreign bodies from five patients. Two of these
      patients had undergone previous unsuccessful attempts at surgical removal in the
      operating room. The technique is cost effective, readily available, and can be
      very helpful in locating difficult-to-find radiolucent foreign bodies at the time
      of surgery.

PMID- 9531415
TI  - Patella position versus length of hamstring muscles in children.
AB  - The results of ultrasonographic examinations of the patellar height in the knee
      joints in children was subjected to analysis. The study aimed at the
      specification of a norm of patellar height in the developmental age, based on the
      tendon-patellar coefficient (analogous to the radiologic measurement according to
      Insall and Salvati). The results of ultrasonographic and clinical examinations of
      114 knee joints performed in 57 healthy children were used for the study. The
      average value of the tendon-patellar coefficient was 1.2 and was independent of
      age or sex. A statistically significant dependence of the coefficient on the
      popliteal angle was demonstrated, which indirectly proved the dependence of the
      coefficient on the length of the hamstrings. In our opinion, the use of
      ultrasonographic tendon-patellar coefficient allows the differentiation of the so
      called physiologic shortening of hamstrings from its pathologic form.

PMID- 9531416
TI  - Radiation exposure during skeletal traction treatment of pediatric femoral
      fractures.
AB  - Radiation-exposure data during femoral fracture management has not been
      previously reported. We report a retrospective analysis of radiation exposure in
      45 patients aged 5-12 years (average, 8.3) with isolated femoral shaft fractures
      treated by 90/90 degrees femoral skeletal traction. Group I had 32 patients aged
      5-9 years (average, 7.3), and group II had 13 patients of an average age of 10.7
      years. Total average radiation dose before casting was 0.699 rads and was
      independent of age and gender. In addition to potential complications of
      tractions and increased hospital stay with attendant fiscal and psychosocial
      burdens, radiation exposure with this type of management, in this series, was
      significant.

PMID- 9531417
TI  - The role of angiography in assessing vascular injuries associated with
      supracondylar humerus fractures remains controversial.

PMID- 9531418
TI  - Cases of congenital dislocation of the knee (CDK) not associated with clubfoot,
      arthrogryposis multiplex congenita, and Larsen's syndrome can be treated
      conservatively.

PMID- 9531419
TI  - The contryphans, a D-tryptophan-containing family of Conus peptides:
      interconversion between conformers.
AB  - We previously characterized contryphan-R, a D-tryptophan-containing octapeptide
      from the venom of Conus radiatus. In this study, we present evidence that the
      contryphan family of peptides is widely distributed in venoms of the fish-hunting
      cone snails. We purified, synthesized and characterized contryphan-Sm from Conus
      stercusmuscarum venom, and obtained molecular evidence for the existence of a
      third peptide, contryphan-P from Conus purpurascens venom ducts. The sequences of
      these three contryphans showed identity in seven of eight amino acids and a
      conserved pattern of post-translational modification. We also demonstrate that
      contryphan-Sm equilibrates between two distinct conformational states.

PMID- 9531420
TI  - Solution conformational analysis of sodium complexed [Gly6]- and [Gly9]
      antamanide analogs.
AB  - To investigate the conformational flexibility of metal-complexed
      cyclodecapeptides, we synthesized and studied two antamanide analogs, in which
      the phenylalanine residue in position 6 or 9 of the sequence was substituted by
      Gly. Previous conformational studies on antamanide suggested that these backbone
      regions are affected by conformational variation. The NMR conformational study
      showed a high degree of flexibility for the two analogs. With sodium ions, on the
      other hand, [Gly9]-antamanide was able to form a fairly stable equimolar complex,
      whereas [Gly6]-antamanide showed a conformational heterogeneity, with one
      prevailing conformer. For the [Gly9]-antamanide analog, the whole NMR data,
      combined with extensive theoretical calculations, were consistent with the
      presence of 1) two beta-turns of type I, centered on Gly9-Phe10 and Ala4-Phe5,
      respectively; 2) a central cavity with a six-carbonyl oxygen cage, optimal for a
      Na+ hexacoordination; 3) strongly H-bonded amide protons for residues 1 and 6,
      both involved in the formation of the two type I beta-turns, which, however,
      exhibited some fluctuations during the molecular dynamics simulations. For the
      [Gly6]-antamanide-Na+ complex the prevailing conformer was consistent with a more
      open structure, with the partial solvent exposure of all the amide protons; that
      is, the Gly residue in position 6 increases the flexibility of this critical site
      more than does the Gly in position 9. These data in some way parallel the results
      of the cytotoxicity tests on B16-F10 transformed cells for the two analogs:
      [Gly9]-antamanide is cytotoxic after 48 h exposure, whereas [Gly6]-antamanide is
      almost inactive. On the contrary, both analogs are practically inactive in vivo
      against phalloidin.

PMID- 9531421
TI  - Identification of a sequence-dependent reversible acylation of tosylarginine in a
      peptidyl-resin reacted with isonicotinyl p-nitrophenylcarbonate.
AB  - In this paper, we report on the identification of an unexpected acylation that
      occurred on the solid phase when a peptide containing an unprotected lysyl and a
      tosyl-protected arginyl residue was treated with a large excess of isonicotinyl p
      nitrophenylcarbonate. NMR and matrix-assisted laser desorption/ionisation -post
      source decay analysis of the purified peptide demonstrated the presence of one
      extra isonicotinyloxycarbonyl (iNoc) group located on the omega nitrogen atom of
      the arginine which was adjacent to the Lys(iNoc). The desired peptide was
      obtained by quantitative removal of the unwanted iNoc group during a brief
      treatment with diluted aqueous hydrazine.

PMID- 9531422
TI  - Fmoc/Trt-amino acids: comparison to Fmoc/tBu-amino acids in peptide synthesis.
AB  - Model peptides containing the nucleophilic amino acids Trp and Met have been
      synthesized with the application of Fmoc/Trt- and Fmoc/tBu-amino acids, for
      comparison. The deprotection of the peptides synthesized using Fmoc/Trt-amino
      acids in all cases leads to crude peptides of higher purity than that of the same
      peptides synthesized using Fmoc/tBu-amino acids.

PMID- 9531423
TI  - Chemical modification monitored by electrospray mass spectrometry: a rapid and
      simple method for identifying and studying functional residues in enzymes.
AB  - A simple method to identify functional amino acids in enzymes is described. This
      method is based on the mass spectrometric detection of molecular weight changes
      as the consequence of chemical modification of enzymes with group-specific
      reagents. Here we report the use of phenylglyoxal, trinitrobenzene sulfonic acid,
      tetranitromethane and diethylpyrocarbonate to identify functional amino acid
      residues. Precise information is obtained about the stoichiometry of reaction,
      and a relationship between the loss of enzyme activity and the amount of chemical
      modification is easily established. Modification sites are located by proteolytic
      digestion of the modified enzyme, followed by peptide mapping based on high
      pressure liquid chromatography using an electrospray mass spectrometer as an on
      line detector. In comparison with more conventional methods, protein modification
      is monitored directly without the need to use radioactively or spectrally
      labelled reagents. The methodology is limited only by the stability of the
      chemically modified species produced. The method has been used to characterise
      the active sites of several shikimate pathway enzymes, and the results obtained
      have been confirmed by site-directed mutagenesis and X-ray crystallography.

PMID- 9531424
TI  - Bufokinin: a substance P-related peptide from the gut of the toad, Bufo marinus
      with high binding affinity but low selectivity for mammalian tachykinin
      receptors.
AB  - A tachykinin peptide, termed bufokinin, was isolated in pure form from an extract
      of the intestine of the toad, Bufo marinus, and its primary structure was
      established as: Lys-Pro-Arg-Pro-Asp-Gln-Phe-Tyr-Gly-Leu-Met.NH2. This sequence
      was confirmed by chemical synthesis and shows four amino acid substitutions (Arg1
      --> Lys,Lys3 --> Arg,Gln5 --> Asp and Phe8 --> Tyr) compared with substance P.
      Binding parameters for synthetic bufokinin and mammalian tachykinins were
      compared using receptor-selective radioligands and crude membranes from rat
      tissues enriched in the NK-1 (submandibular gland) , NK-2 (stomach fundus) and NK
      3 (brain) receptors. In terms of inhibiting the binding of the selective
      radioligands, bufokinin (Kd = 0.3 nM) was 1.8-fold more potent than substance P
      at the rat NK-1 site, but it was only 2-fold less potent (Kd = 2.8 nM) than
      neurokinin A at the NK-2 site and only 2-fold less potent (Kd = 48 nM) than
      neurokinin B at the NK-3 site. Thus, bufokinin shows relatively high affinity but
      lack of selectivity for all three tachykinin binding sites in rat tissues.

PMID- 9531425
TI  - A peptide inhibitor of cholesteryl ester transfer protein identified by screening
      a bacteriophage display library.
AB  - We screened a bacteriophage display library of random decapeptides to identify
      peptide inhibitors of cholesteryl ester transfer protein (CETP). After affinity
      selection against CETP, bacteriophage-infected Escherichia coli were plated at
      clonal density and 36 random clones were isolated. Analysis of the relevant
      portion of the bacteriophage DNA from a group of 12 clones that had a relatively
      high affinity for CETP revealed that the corresponding amino acid sequences of
      the displayed peptides exhibited an ... Xaa-Arg-Met-Arg-Tyr-Xaa ... composite
      motif. Based on those results, decapeptides from this group were synthesized and
      one of them, DP1 (NH2-VTWRMWYVPA-COOH), inhibited CETP-catalyzed transfer of
      cholesteryl esters and triglycerides. Amino- and carboxy-terminal truncations of
      DP1 demonstrated that the original decapeptide could be reduced to a pentapeptide
      without loss of either its ability to bind to CETP or its ability to inhibit CETP
      mediated lipid transfer. That pentapeptide, NH2-WRMWY-COOH (WRMWY, PNU-107368E),
      binds directly to CETP and its inhibition is consistent with that of a
      competitive inhibitor of CETP with a Ki of 164 microM. WRMWY or modified versions
      of this peptide may be useful in studying the interactions between CETP and
      plasma lipoproteins.

PMID- 9531426
TI  - NMR analysis of a potent decapeptide agonist of human C5a anaphylatoxin.
AB  - A NMR investigation in H2O, TFE and DMSO of a conformationally constrained,
      potent decapeptide agonist of human C5a, YSFKDMPLaR (C5a65-74, Y65, F67, P71, D
      Ala73) showed that its N-terminal region (YSFKD) exhibited an extended backbone
      conformation in H2O and a more twisted conformation in both TFE/H2O (30:70, v/v;
      referred to as TFE) and DMSO. The C-terminal region (MPLaR) of the peptide
      adopted compact, turn-like structures. In H2O, the C-terminal region adopted a
      type II beta-turn or a distorted type V/II beta-turn involving residues PLaR. In
      the distorted type V/II beta-turn, Leu72 exhibited a conformation typical of a
      type V beta-turn, whereas D-Ala73 exhibited a conformation typical of a type II
      beta-turn. The distorted type V/II beta-turn overlapped with an inverse gamma
      turn involving residues MPL. In DMSO, the C-terminal region had the analogous
      inverse gamma-turn and the V/II beta-turn found in H2O. In many of the DMSO
      structures, two inverse gamma-turns in the MPL and PLa positions formed a double
      inverse gamma-turn. None of the turns observed in H2O were present in TFE.
      However, in TFE, the PLa residues formed an inverse gamma-turn. Overall, the turn
      like structural motifs in the C-terminal region of the peptide in both H2O and
      DMSO (but not in TFE) agreed with the biologically important conformations
      obtained earlier by the structure-function analysis of a panel of C5a agonist
      peptides. These motifs may represent key structural elements important for C5a
      agonist activity and may be used to design the next generation of C5a agonist and
      antagonist analogues.

PMID- 9531427
TI  - Conformational and topological requirements of cell-permeable peptide function.
AB  - Cell-permeable peptide import recently was developed to deliver synthetic
      peptides into living cells for studying intracellular protein functions. This
      import process is mediated by an N-terminal carrier sequence which is the
      hydrophobic region of a signal peptide. In this study, the conformational
      consequence of the interaction of cell-permeable peptides with different mimetic
      membrane environments was investigated by circular dichroism analysis. We showed
      that cell-permeable peptides adopted alpha-helical structures in sodium dodecyl
      sulfate (SDS) micelles or aqueous trifluoroethanol (TFE). The potency of these
      peptides in forming helical structures is higher in an amphiphilic environment
      (SDS) than in a hydrophobic environment (TFE), suggesting that some hydrophilic
      molecules associated with the cell membrane may be involved in peptide import. We
      also studied topological requirements of cell-permeable peptide function. We
      demonstrated that peptides containing the carrier sequence in their C-termini can
      also be imported into cells efficiently. This important discovery can avoid
      repetitious synthesis of the membrane-translocating sequence for peptides with
      different functional cargoes and is potentially useful for developing a cell
      permeable peptide library. Finally, we showed that, when a retro version of the
      carrier sequence was used, the peptide lost its translocating ability despite
      retaining a high content of alpha-helical structure in mimetic membrane
      environments. This suggests that the propensity of peptides to adopt a helical
      conformation is required but not sufficient for cellular import and that other
      structural factors such as the side-chain topology of the carrier sequence are
      also important. Our studies together contribute to the more rational design of
      useful cell-permeable peptides.

PMID- 9531428
TI  - Conformational behaviour of the TraM headpiece.
AB  - The structure of the headpiece of the TraM protein was investigated in different
      solvents. The very first 22 amino acids which alternate in their hydrophilic and
      hydrophobic character formed a helical structure in the presence of a membrane
      mimetic. In water alone the structure was flexible with a small amount of
      helicity according to circular dichroism measurements, whereas a loop structure
      was observed in dimethyl sulphoxide.

PMID- 9531430
TI  - Cerebral embolism and epileptic seizures--the role of the embolic source.
AB  - OBJECTIVES: To study the clinical outcome of patients with epileptic seizures due
      to ischemic stroke (IS) of cardiac or artery-to-artery embolism. METHODS:
      Seizures due to IS of cardiac or artery-to-artery embolism are differentiated by
      clinical, neuroimaging and cardiovascular test data. RESULTS: From 174 cases with
      supratentorial IS, 13 patients suffered from epileptic seizures due to cardiac
      embolism, 11 patients due to artery-to-artery embolism. The patients with cardiac
      IS showed an equal sex distribution and EEG abnormalities in 6 patients, the
      initial seizure occurred on average after 222 days (SD, +/-69 days). Among the 11
      patients with artery-to-artery embolic IS, there were 9 males and 2 females and
      EEG abnormalities in 10 patients. The initial seizure occurred on average after
      447 days (SD, +/-177 days). CONCLUSION: In seizures due to artery-to-artery
      embolism, there is a male preponderance and a higher incidence of EEG
      abnormalities, symptomatic seizures appear later compared to IS due to cardiac
      embolism.

PMID- 9531429
TI  - FDG-PET and MRI in temporal lobe epilepsy: relationship to febrile seizures,
      hippocampal sclerosis and outcome.
AB  - OBJECTIVE: To correlate the volumetric head magnetic resonance imaging (MRI) and
      fluorodeoxyglucose-positron emission tomography (FDG-PET) scan findings with the
      history, intracarotid amobarbital procedure, pathology, and outcome in patients
      with medically refractory temporal lobe epilepsy. MATERIAL AND METHODS: Thirty
      eight patients with temporal lobe epilepsy treated surgically following a
      comprehensive presurgical evaluation. Follow-up ranged from 12 to 44 months.
      RESULTS: Volumetric MRI showed ipsilateral hippocampal atrophy in 29 (76%), and
      PET scan showed ipsilateral temporal hypometabolism (PET-TH) in 31 (81.5%) of
      patients. Eighty-three percent of those patients with hippocampal sclerosis on
      MRI (MRI-HS) had ipsilateral PET-TH. Sixty-six percent of patients with MRI-HS
      had a history of prolonged febrile convulsions or a childhood febrile illness
      accompanied by convulsions, and 77% of patients with MRI-HS had pathologically
      proven hippocampal sclerosis (HS). Ninety percent became seizure free or had rare
      seizures. CONCLUSION: FDG-PET scans and head MRIs were complementary; 95% of
      patients had either MRI-HS or temporal hypometabolism. MRI-HS correlated with a
      history of febrile seizures and pathologically demonstrated hippocampal
      sclerosis. Ninety-three percent of patients had focal functional deficits on the
      epileptogenic side. Concordance between PET temporal hypometabolism and MRI-HS
      correlated with better outcome.

PMID- 9531431
TI  - Juvenile myoclonic epilepsy: clinical and EEG features.
AB  - We aimed to characterize the clinical profile and EEG features of 43 patients
      with juvenile myoclonic epilepsy. In a retrospective design we studied the
      records of, and re-interviewed, 43 patients diagnosed with JME from the epilepsy
      clinic data base. Furthermore, available EEGs were re-evaluated. Of the patients
      72% were female and 28% male. Average age of onset was 13 (5.5-22) years for
      absences, 16 (5.2-25) years for myoclonic seizures, and 16 (8-29) years for
      generalized tonic-clonic seizures. Forty-two percent reported asymmetric or
      unilateral myoclonic jerks. Commonly reported precipitating factors were sleep
      deprivation (84%), stress (70%), and alcohol consumption (51%). EEG findings
      included rapid spike-wave and polyspike-wave.

PMID- 9531432
TI  - Pregnancy and epilepsy: a retrospective study of 151 pregnancies.
AB  - OBJECTIVE: We studied the course of pregnancy in women with epilepsy to identify
      possible risk factors which might complicate the epilepsies and pregnancy
      outcomes. MATERIAL AND METHODS: Data were collected retrospectively from the
      records of 151 pregnancies in 124 women with epilepsy from 1978-1992. Epilepsy
      variables were compared with that of non-pregnant women with epilepsy matched for
      age. Obstetric and neonatal variables were compared with those of all deliveries
      in the same unit from 1979-1992 (n=38,983). RESULTS: Pregnancy among patients
      with epilepsy was more likely to occur in women with relatively mild epilepsy. In
      12% of the pregnancies, the women were untreated while 71% were on monotherapy.
      Twenty-one percent had increased seizure frequency during the pregnancy.
      Perinatal deaths among newborns of epileptic mothers (1.3%) was more frequent but
      not significantly increased compared to the background population of 0.5% (95% CI
      0.2-4.7). A total of 5.3% had congenital malformations compared to 1.5% in the
      controls (95% CI 2.3-10.3). No neural tube defects were observed. Maternal
      treatment with phenytoin was significantly related to the occurrence of
      congenital malformations, P=0.04. CONCLUSIONS: Most women with epilepsy have an
      uncomplicated pregnancy and normal healthy offsprings. Maternal treatment with
      phenytoin might be associated with congenital malformations. No other risk
      factors could be identified.

PMID- 9531433
TI  - The significance of Epstein-Barr virus seropositivity in multiple sclerosis
      patients?
AB  - The objective of this study was to evaluate and investigate the significance of
      the previously found 100% seropositivity toward Epstein-Barr virus (EBV) found in
      multiple sclerosis (MS) patients in contrast to healthy controls. Using a
      commercially available ELISA-test (Biotest), which differentiates infections with
      EBV into previous infections, primary infections, reactivated infections and no
      previous infection, we found 137 of 138 MS patients and 124 of 138 healthy
      controls seropositive. A primary infection in 4 of the 124 EBV seropositive
      healthy controls in contrast to no primary infections in the MS EBV seropositive
      group was significant (P=0.049652, Fishers exact test). This may be suggestive of
      a lack of primary infections in MS patients, and thus strengthens the idea that
      MS patients are infected with EBV before development of MS. Further studies are
      in progress to analyse whether EBV infection is a prerequisite for the
      development of this disease.

PMID- 9531434
TI  - Long-term intraduodenal infusion of a water based levodopa-carbidopa dispersion
      in very advanced Parkinson's disease.
AB  - OBJECTIVE: To evaluate the effects of continuous duodenal infusion of levodopa
      over time on the disabling fluctuations in motor performance in advanced
      parkinsonian patients. It has earlier been demonstrated that these fluctuations
      can be reduced by keeping the plasma concentration of levodopa constant. MATERIAL
      AND METHODS: In view of the low water solubility of levodopa a stable dispersion
      of the drug was developed and used for continuous intraduodenal infusion in
      patients with advanced Parkinson's disease. Nine patients were evaluated with
      respect to an optimal oral treatment, during nasoduodenal infusion by a portable
      pump and then followed for 6 months to 2 1/2 years when treated via
      transabdominal infusion. Upon each test occasion, over 2 non-consecutive days,
      objective movement analysis by means of an opto-electronic system was applied
      every 15-20 min and video recordings performed twice every h. On several test
      occasions plasma levodopa concentrations were analysed every 15 min. RESULTS: The
      patients showed improvement and decreased variance of their motor function. In
      the 2 patients followed over a period of 2 1/2 years levodopa plasma
      concentration showed reduced fluctuations on infusion and the levodopa
      consumption as well as mean levodopa plasma concentration decreased. CONCLUSION:
      Continuous duodenal infusion of levodopa is an alternative treatment strategy for
      patients with advanced Parkinson's disease when conventional therapy has failed.

PMID- 9531435
TI  - Identification in Israel of 2 Jewish Creutzfeld-Jakob disease patients with a 178
      mutation at their PrP gene.
AB  - Among the dozen known mutations in the PrP gene which segregate with the
      inherited prion diseases, only 2 mutations have been described in Israel so far:
      the codon 200 mutation in Creutzfeldt-Jakob disease (CJD) affected Libyan Jews,
      and the codon 102 mutation in 1 Jewish Gerstmann-Straussler-Scheinker (GSS)
      affected pedigree of German origin. We report here 2 unrelated CJD178 cases
      affected by a unique phenotype: aphemia, apraxia, uncontrolled laugh and no
      ataxia. As opposed to other CJD178 patients, in these patients, the signal
      transduction protein 14-3-3, recently suggested as a CJD marker, was detected in
      the cerebrospinal fluid samples by immunostaining. The D178N mutation, known to
      be linked to 2 different phenotypes: Fatal Familial Insomnia (FFI) and CJD, was
      not described so far among Jews. The phenotype reported here, although it shares
      a common Va1129/Asn178 haplotype with the previously described CJD178, may point
      to a different clinical subtype of CJD178.

PMID- 9531436
TI  - The whiplash syndrome: a psychophysiological and neuropsychological study towards
      attention.
AB  - Whiplash patients often have physical, psychosomatic and cognitive complaints,
      although clear neurological and neuropsychological signs of damage are absent.
      However, in some studies a functional loss of attention was found. In order to
      compare attentional dysfunctions in whiplash patients with age-matched controls,
      attention was measured neuropsychologically with the aid of the PASAT, and
      psychophysiologically with the aid of the prepulse inhibition paradigm. In
      addition, the reactivity for intense acoustic stimulation was investigated. The
      POMS and the SCL-90 were used to evaluate psychological and somatic signs. The
      results showed that whiplash patients (n=24) had lower scores on the PASAT and
      higher scores on the questionnaires compared to healthy controls (n=21). However,
      no group differences could be determined on the psychophysiological variables.
      Furthermore, the PASAT and prepulse inhibition data did not correlate. The lower
      PASAT scores indicate that whiplash patients seem to have deteriorated divided
      attention, but an attention deficit as measured with the prepulse inhibition
      paradigm is not disclosed. Finally, there were no signs of a heightened
      reactivity of the auditory system, which casts doubts on a presumed heightened
      sensitivity for sound in whiplash patients.

PMID- 9531437
TI  - Comparison of IgM-MGUS and IgG-MGUS polyneuropathy.
AB  - OBJECTIVE: To compare the clinical and electrodiagnostic features and response to
      treatment in patients with IgM-MGUS and IgG-MGUS associated polyneuropathy.
      MATERIAL AND METHODS: Retrospective review of 34 consecutive patients with MGUS
      associated neuropathy evaluated over 5 years. RESULTS: There were 19 patients
      with IgM-MGUS and 15 with IgG-MGUS. There were no differences in age, duration of
      symptoms, or distribution of motor and sensory symptoms or signs. IgM-MGUS
      patients had prolonged distal latencies of the median and ulnar motor potentials,
      greater slowing of the peroneal nerve conduction velocity and more often absent
      ulnar sensory potentials. Half of the patients in both groups improved following
      immunotherapy. CONCLUSION: IgM-MGUS patients had more severe demyelination on the
      nerve conduction studies, but there were no clinical features that differentiated
      the 2 groups. IgM and IgG-MGUS patients improved with plasma exchange and other
      immune therapies. Anti-MAG antibodies failed to distinguish a subgroup of
      patients with IgM-MGUS neuropathy.

PMID- 9531438
TI  - The diagnostic importance of eosinophil granulocytes in the CSF of children with
      ventricular-peritoneal shunt systems.
AB  - We investigated the occurrence of cerebrospinal fluid (CSF) eosinophilia in
      patients with ventriculo-abdominal shunt systems with regard to possible
      infection. For this purpose, we examined the CSF of 83 children at the time of
      shunt obstruction or malfunction. In 32 children (38.6%) we found more than 4% of
      eosinophil granulocytes in the CSF with a maximum of 76%. In 15 of these 32
      children the CSF was sterile, whereas in 17 patients bacterial infection was
      present. In the CSF of 16 of those 17 children, Staph. epidermidis was
      cultivated. There was statistically significant correlation between positive
      Staph. epidermidis culture and the occurrence of CSF eosinophilia (P<0.05). The
      occurrence of CSF eosinophilia in patients with ventriculo-peritoneal shunts is
      well known and was mostly attributed to an allergic reaction. Our findings
      support the theory of an infectious etiology of the eosinophilia and are thus in
      line with new American and French studies. We believe that CSF eosinophilia
      indicates a persistent infection of the central nervous system by the
      contaminated shunt system. As the organism which is the most common cause we
      cultured Staph. epidermidis.

PMID- 9531440
TI  - Possible role of cAMP, cGMP and [Ca2+]i during NANC relaxation in the cat airway
      smooth muscle.
AB  - To investigate the possible role of cyclic nucleotides and [Ca2+]i in non
      adrenergic non-cholinergic (NANC) relaxations evoked by electrical field
      stimulation (EFS) in the cat airway, we studied the effects of specific
      phosphodiesterase (PDE) type IV or V inhibitors on the biphasic-NANC relaxations,
      the correlation between NANC relaxation and changes in intracellular levels of
      cAMP and cGMP ([cAMP]i and [cGMP]i), and measured changes in [Ca2+]i during the
      NANC relaxation. EFS (repetitive stimuli at 20 Hz, 1 or 4 ms pulse duration, 50
      V) applied to the bronchial smooth muscle during contraction induced by 5-HT (10(
      5) M) in the presence of atropine (10(-6) M) and guanethidine (10(-6) M) elicited
      biphasic NANC relaxations. Zaprinast (> 3 x 10(-7) M), a specific PDE type V
      inhibitor, preferentially enhanced the amplitude of the first component of the
      NANC relaxations. However, rolipram (> 3 x 10(-7) M) enhanced both the first and
      second component of the NANC relaxation to a similar extent. In the trachea, EFS
      evoked monophasic NANC relaxation accompanied by a concomitant accumulation of
      [cAMP]i and [cGMP]i. Pretreatment with rolipram (3 x 10(-6) M) enhanced the
      accumulation of [cAMP]i and amplitude of NANC relaxation evoked by EFS. However,
      zaprinast did not affect the amplitude of NANC relaxation although it
      significantly increased the levels of [cGMP]i. Nomega-Nitro-L-arginine
      methylester (L-NAME; 10(-5) M) completely suppressed the accumulation of [cGMP]i
      but only partly suppressed the NANC relaxation evoked by EFS. In contrast, EFS
      significantly enhanced [cAMP]i in the presence of L-NAME. During NANC relaxation,
      time-dependent decrease in [Ca2+]i occurred, which was partly suppressed by L
      NAME. These results indicate that NANC relaxation is associated with concomitant
      accumulation in both [cAMP]i and [cGMP]i, and decrease in [Ca2+]i. However, the
      timing of the action of [cGMP]i and [cAMP]i in NANC relaxations differs in the
      central and peripheral airway.

PMID- 9531441
TI  - Inhibition of sympathetic cholinergic vasodilatation by a selective NPY Y2
      receptor agonist in the gracilis muscle of anaesthetised dogs.
AB  - Neuropeptide Y (NPY) is known to be co-stored and co-released from sympathetic
      nerve terminals. In the cardiovascular system NPY acts on two main receptor
      subtypes. At the postjunctional or Y1 receptor NPY causes constriction directly
      in addition to potentiating other vasoconstrictor agents. NPY acting at the
      prejunctional, or Y2 receptor, inhibits the release of neurotransmitter from
      autonomic nerve terminals. In these experiments we used the selective Y2 receptor
      agonist N-acetyl[Leu28,Leu31]NPY24-36 to examine the role of NPY in the
      modulation of sympathetic vascular control in skeletal muscle in anaesthetised
      dogs. No systemic pressor or local constrictor activity was observed in response
      to N-acetyl[Leu28, Leu31]NPY24-36 administration, therefore allowing us to
      examine the neuroinhibitory actions of NPY in the absence of direct vascular
      effects on blood flow. Stimulation of the sympathetic nerves to the gracilis
      muscle engages both sympathetic cholinergic and sympathetic adrenergic fibres and
      produces an initial vasodilatation followed by a slower vasoconstriction. Nerve
      evoked vasodilatation was inhibited by over 50% in the presence of the selective
      NPY Y2 agonist N-acetyl[Leu28,Leu31]NPY24-36. This dilatation was abolished by
      atropine, confirming its cholinergic nature. N-Acetyl[Leu28,Leu31]NPY24-36 was
      found to have no effect on nerve evoked vasoconstriction. The results demonstrate
      a NPY Y2-receptor mediated inhibition of nerve evoked sympathetic cholinergic
      vasodilatation but not of sympathetic vasoconstriction.

PMID- 9531439
TI  - Exteroceptive suppression of masseter muscle: assessment of two methods for
      quantitating suppression periods.
AB  - OBJECTIVES: The late exteroceptive suppression period (ES2) of the masseter
      muscle is conventionally quantified by a combination of measures of duration,
      amplitude, or mean activity. The combination of measures makes it difficult to
      compare ES2s obtained from different set-ups. An unbiased method for quantitating
      ES2 is introduced allowing ranking of ES2s. The introduced method is utilized to
      evaluate stimulus and recording conditions under which ES2 is maximal. MATERIAL
      AND METHODS: Fifteen male volunteers participated in 3 experiments designed to
      determine the effect of level of teeth clenching, stimulus intensity, and
      perceived pain intensity on the ES2. RESULTS: Coefficients of variance (1 h/1
      month) were: duration: 11%/43%, latency: 9%/12%, and magnitude of suppression:
      11%/12%. A level of teeth clenching of 66% of maximal voluntary bite force, and a
      stimulus intensity below pain detection threshold was associated with maximal
      magnitude of suppression of ES2. CONCLUSION: The introduced method is
      reproducible and allows ranking and stimulus-response estimations of ES2. It is
      suggested that ES2 does not reflect activity along the nociceptive pathways in
      the trigeminal region.

PMID- 9531442
TI  - Brainstem cells of origin of physiologically identified cardiopulmonary nerves in
      the rhesus monkey (Macaca mulatta).
AB  - The distributions of brainstem cells of origin of the cervical vagus nerve, its
      cervical and thoracic branches, and of neurons projecting to the cricothyroid
      muscle and the stomach wall were identified and compared following injections of
      horseradish peroxidase (HRP) in 18 Rhesus monkeys. Physiologically and/or
      anatomically identified cardiopulmonary nerves were injected with 3-20 microl of
      HRP to identify the locations of vagal preganglionic cardioinhibitory neurons in
      10 of these monkeys. After injections into cardiopulmonary nerves, retrogradely
      labelled cells were concentrated ipsilaterally in the most lateral parts of the
      dorsal motor nucleus of the vagus nerve (DMV) and in the ventrolateral nucleus
      ambiguus (NA). Fewer labelled neurons were identified close to or in the
      principal (dorsal) division of the NA and in the intermediate zone between the
      DMV and NA. The results indicate that monkey cardiopulmonary nerves have multiple
      origins; their somata are located primarily in the ventrolateral NA and to a
      lesser extent in the lateral DMV. In monkeys, there is a stronger representation
      in the lateral DMV than in cat, dog and pig. The viscerotopic organization of the
      cells of origin of primate vagal nerves is similar to that in other species. The
      cells of origin of vagal projections to the superior laryngeal nerve and
      cricothyroid muscle were located in the NA rostrally to those of the inferior
      laryngeal nerve. Injections into the superior laryngeal nerve also resulted in
      significant labelling in the DMV and intermediate zone (IZ). The cells of origin
      of projections to the anterior stomach wall were restricted to the DMV with a
      bilateral distribution of labelled cells, concentrated medially in the nucleus.

PMID- 9531443
TI  - Neurochemical characterization and distribution of enteric GABAergic neurons and
      nerve fibres in the human colon.
AB  - GABA, somatostatin and enkephalin are neurotransmitters of enteric interneurons
      and comprise part of the intrinsic neural circuits regulating peristalsis. Within
      the relaxation phase of reflex peristalsis, nitric oxide (NO) is released by
      inhibitory motor neurons and perhaps enteric interneurons as well. Previously, we
      identified by GABA transaminase (GABA-T) immunohistochemistry, a subpopulation of
      GABAergic interneurons in the human colon which also contain NO synthase activity
      and hence produce NO. In this study, we have examined further the capacity for
      cotransmission within the GABAergic innervation in human colon. The expression of
      two important neuropeptides within GABAergic neurons was determined by combined
      double-labelled immunocytochemistry using antibodies for GABA-T, enkephalin and
      somatostatin, together with the demonstration of NO synthase-related NADPH
      diaphorase staining in cryosectioned colon. Both neuropeptides were found in
      GABAergic neurons of the colon. The evidence presented herein confirms the
      colocalization of NO synthase activity and GABA-T immunoreactivity in
      subpopulations of enteric neurons and further allows the neurochemical
      classification of GABAergic neurons of the human colon into three subsets: (i)
      neurons colocalizing somatostatin-like immunoreactivity representing about 40% of
      the GABAergic neurons, (ii) neurons colocalizing enkephalin-like
      immunoreactivity, about 9% of the GABAergic neurons and (iii) neurons
      colocalizing NO synthase activity, about 23% of the GABAergic neurons. This
      division of GABAergic interneurons into distinct subpopulations of neuropeptide
      or NO synthase containing cells is consistent with and provides an anatomical
      correlate for the pharmacology of these transmitters and the pattern of
      transmitter release during reflex peristalsis.

PMID- 9531444
TI  - Effects of omega-conotoxin GVIA on cardiac sympathetic nerve function.
AB  - Using a cardiac dialysis technique, the effects of omega-conotoxin GVIA (N-type
      Ca2+ channel blocker) on cardiac sympathetic nerve function was examined in
      anesthetized cats. Dialysis probes were implanted in the left ventricular wall
      and the concentration of dialysate norepinephrine (NE) served as an indicator of
      NE output at cardiac sympathetic nerve endings. Administration of omega-conotoxin
      GVIA (10 microg/kg i.v.) suppressed dialysate NE responses to the nerve
      stimulation. The ouabain (1 microM) induced NE increment was less markedly
      suppressed by omega-conotoxin GVIA. Furthermore, omega-conotoxin GVIA neither
      influenced neuronal NE uptake nor tyramine induced release of NE from stores.
      These findings suggest that the neuronal effect of omega-conotoxin GVIA is
      attributable to a reduction of exocytotic NE release without alterations of
      neuronal NE uptake or storage. Cardiac dialysis with omega-conotoxin GVIA offers
      a new approach for the discrimination between Ca2+ dependent exocytotic and non
      exocytotic NE release.

PMID- 9531445
TI  - Inhibition of muscle sympathetic outflow following transcranial cortical
      stimulation.
AB  - The possible contribution of cerebral cortical activity to sympathetic outflow to
      the muscle vascular bed was assessed in normal human subjects. Muscle sympathetic
      activity was recorded from motor fascicles of the peroneal nerve in 8 subjects
      while transcranial magnetic stimulation was applied over the vertex, or
      unilaterally over the hand area of cortex. By triggering the cortical stimulus
      from the R-wave of the ECG and introducing delays of 0-600 ms between the trigger
      and the stimulus, we found that a single cortical stimulus delayed by 200-400 ms
      caused a pronounced inhibition of one pulse-synchronous sympathetic burst.
      Stimulation over the vertex was more effective than stimulation over the hand
      area of cortex. In addition to this inhibition of muscle sympathetic outflow,
      brain stimulation caused an increase in cutaneous sympathetic activity, both
      sudomotor (sweating) and vasoconstrictor (decrease in skin blood flow). We
      suggest that the cerebral cortex may normally suppress muscle sympathetic outflow
      and speculate that lesions that interrupt this source of inhibition (such as
      those caused by stroke) may result in an augmented muscle sympathetic outflow.

PMID- 9531446
TI  - Simultaneous changes of rhythmic organization in brainstem neurons, respiration,
      cardiovascular system and EEG between 0.05 Hz and 0.5 Hz.
AB  - Several neurons from different regions of the brainstem of anesthetized dogs were
      simultaneously recorded, together with various parameters of the cardiovascular
      system, respiration, efferent sympathetic neural activities and cortical
      activity. Often rhythmic changes of activity in the range 0.05-0.5 Hz could be
      observed in the simultaneously recorded signals. The rhythms were analysed in
      time domain and by power spectra and their changes depicted over the time. The
      most striking rhythms between 0.05 Hz and 0.5 Hz are the respiratory rhythm and
      those rhythms that originate in reticular neurons of the common brainstem system
      as well as their respective harmonics, i.e. the ranges around the integer
      multiple frequencies of these basic rhythms. The observed oscillations can vanish
      and reappear at times. Frequencies of basic oscillations and harmonics and their
      amplitudes are subject to distinct slow modulations. These modulations can have
      irregular as well as regular courses. The different rhythms can appear separately
      or simultaneously in the single signals. The most important phenomenon to be
      observed is that the rhythms mutually influence their frequencies, which follows
      the rules of 'relative coordination' as described by E. v. Holst. Such changes of
      rhythmic activities generally also concern the ranges of harmonics of the basic
      rhythms. Rhythmic influences on peripheral functional systems, e.g. the
      cardiovascular system, are most distinct at times when the different rhythms
      overlap in their frequency ranges. This holds not only for the ranges of basic
      frequencies, but also for the ranges of their harmonics. Further it was found
      that rhythms with the same basic frequencies may not only appear simultaneously,
      but also at various times in the different functional systems. The temporal
      course of changes of these rhythms, their interactions and their influence on the
      processing of cardiac rhythmic neuronal discharge patterns is demonstrated. The
      meaning of the mutually influencing rhythms for the functional organization of
      central nervous structures is discussed.

PMID- 9531447
TI  - Vagal nerve stimulation during muscarinic and beta-adrenergic blockade causes
      significant coronary artery dilation.
AB  - Vasoactive intestinal peptide (VIP) is present in post-ganglionic vagal nerve
      fibers in the coronary arteries and right ventricle but no significant amounts
      are found in the left ventricle. We determined the effects of VIP, released
      endogenously from cardiac vagal nerves, on the circumflex mean coronary artery
      pressure and on right and left ventricular (RV and LV) contractility (dP/dtmax)
      and relaxation (dP/dtmin). In 20 anesthetized, open chest mongrel dogs, the
      cervical vagus nerves and cardiac sympathetic ansa subclaviae were isolated and
      transected. Electrodes were applied to the cardiac segments of the right and left
      vagus nerves for subsequent stimulation. The muscarinic and beta-adrenergic
      receptors were blocked with atropine and propranolol, respectively. The heart
      rate was controlled by either producing atrioventricular node block in 10 dogs
      and pacing the ventricles (series 1) or by right atrial pacing in 10 separate
      dogs (series 2). Coronary artery blood flow was controlled by perfusing the
      circumflex coronary artery in each dog with femoral arterial blood at a
      controlled flow rate. Coronary artery pressure, ventricular and aortic pressures
      and dP/dt were continuously measured. Experiments were performed prior to and
      after the administration of [4Cl-D-Phe6,Leu17]VIP, a sensitive and selective VIP
      antagonist. Vagal nerve stimulation at 20 Hz (0.5 ms, 20 V) for 5 min
      significantly decreased the circumflex mean coronary artery pressure by 17% from
      the control value of 95+/-2 mmHg in series 1 and by 13% from the control value of
      109+/-2 mmHg in series 2 (both p < 0.005). Aortic, LV and RV systolic and end
      diastolic pressures, LV dP/dtmax and dP/dtmin, and the EKG did not change. In
      contrast, RV dP/dtmax and dP/dtmin increased by 22% (p < 0.04) and 23% (p <
      0.02), respectively, in series 1 and by 26% (p < 0.02) and 33% (p < 0.01),
      respectively, in series 2. The VIP antagonist, [4Cl-D-Phe6,Leu17]VIP, directly
      injected into the left circumflex coronary artery, had no effect on coronary,
      aortic or ventricular pressures, ventricular dP/dt or the EKG. However, 20 Hz
      vagal stimulation in the presence of the VIP antagonist did not decrease
      circumflex mean coronary artery pressure. In addition, vagal stimulation, in the
      presence of the VIP antagonist, had no effect on LV pressures or dP/dt but
      increased RV dP/dtmax and dP/dtmin. RV dP/dtmax increased by 16% (p < 0.01) and
      RV dP/dtmin increased by 22% (p < 0.04), respectively, in series 1 and by 27 and
      24%, respectively, in series 2 (both p < 0.01). Vagal nerve stimulation during
      muscarinic and beta-adrenergic blockade releases VIP or a 'VIP-like' substance
      that significantly decreases circumflex coronary artery vascular resistance and
      increases RV dP/dtmax and dP/dtmin.

PMID- 9531448
TI  - Contributions of tidal lung inflation to human R-R interval and arterial pressure
      fluctuations.
AB  - We studied the effects of mechanical lung inflation on respiratory frequency R-R
      interval and arterial pressure fluctuations in nine healthy young adults
      undergoing elective orthopedic surgery. We conducted this research to define the
      contribution of pulmonary and thoracic stretch receptor input to respiratory
      sinus arrhythmia. We compared fast Fourier transform spectral power during three
      modes of ventilation: (1) spontaneous, frequency-controlled (0.25 Hz) breathing,
      (2) intermittent positive pressure ventilation (0.25 Hz, with a tidal volume of 8
      ml/kg) and (3) high frequency jet ventilation (5.0 Hz, 2.5 kg/cm2), after
      sedation and vecuronium paralysis. Mean R-R intervals, arterial pressures and
      arterial blood gas levels were comparable during all three breathing conditions.
      Respiratory frequency systolic pressure spectral power was comparable during
      spontaneous breathing and conventional mechanical ventilation, but was
      significantly reduced during high frequency jet ventilation (P < 0.05).
      Respiratory frequency R-R interval spectral power (used as an index of
      respiratory sinus arrhythmia) declined dramatically with sedation and muscle
      paralysis (P < 0.05), but was greater during conventional mechanical, than high
      frequency jet ventilation (P < 0.05). These results suggest that although phasic
      inputs from pulmonary and thoracic stretch receptors make a statistically
      significant contribution to respiratory sinus arrhythmia, that contribution is
      small.

PMID- 9531449
TI  - Free plasma catecholamines in spinal cord injured persons with different injury
      levels at rest and during exercise.
AB  - Spinal cord lesion leads to an interruption of pathways from brain to the
      peripheral sympathetic nervous system, which results in pathological changes in
      sympathetic innervation. Free epinephrine (E), norepinephrine (NE) and dopamine
      (DA) were measured in 30 tetraplegics (TETRA), 15 high-lesion paraplegics (T1 and
      T4, HPARA), 15 paraplegics with injuries between T5 and T10 (MPARA), 15 low
      lesion paraplegics (below T10, LPARA) and 16 non-handicapped control persons (C)
      at rest, at 60 and 100% of maximal oxygen consumption during graded wheelchair
      ergometry (WCE). The TETRA showed significant lower E and NE levels at rest and
      only slight increases during physical exercise. The E and NE concentrations of
      the paraplegics with a lesion below T5 were significantly higher than those of
      the high-lesion paraplegics, as well as those of the control persons at every
      point in the study. All paraplegics and the control persons showed, at submaximal
      and maximal exercise, a significant increase in NE. Only a slight increase in E
      in HAPRA was shown. No differences were found at rest and during exercise in E
      and NE levels in the MPARA and LPARA. No significant differences were found in
      the dopamine concentration at rest or during exercise for any of the groups. In
      summary, different levels of lesion and the resulting interruption to sympathetic
      pathways in the spinal cord are decisive factors in the degree of impairment of
      sympathetic innervation in SCI persons. Tetraplegics show less preganglionic
      resting activity because of interruption of impulses from central centers and no
      considerable stimulation of the sympathetic nervous system during maximal
      exercise. Individuals with high paraplegia have a partial impairment of
      catecholamine release, especially of epinephrine, at rest and during exercise.
      Paraplegics with a lesion level below T5 showed an augmented basal and exercise
      induced upper spinal thoracic sympathetic activity in comparison to control
      persons.

PMID- 9531450
TI  - Visceral orthostatic hypotension in patients with severe autonomic dysfunction.
AB  - Although changes in the blood flow of the cerebral vessels and the peripheral
      vessels in the extremities after changing body postures have been well examined
      in patients with orthostatic hypotension (OH), such changes in visceral vessels
      have not been well investigated. To elucidate the effect of autonomic
      dysfunctions on changes in the abdominal blood flow, the blood flow velocity of
      the portal vein was measured by Doppler ultrasonography in 11 patients with
      familial amyloidotic polyneuropathy (FAP) (Met30), 3 with pandysautonomia, 1 with
      Shy-Drager syndrome, and 10 healthy controls, in the supine and at the upright
      position. Among the 15 patients with the above-mentioned autonomic disorders, 5
      of the patients showed a marked decrease in blood flow after standing, and one of
      these 5 patients exhibited transient hepatic and intestinal ischemia during
      intensive rehabilitation because of a severe decrease in visceral blood flow.
      Another 7 patients exhibited moderate decreases in the blood flow after standing.
      In contrast, no such change was observed in the 10 healthy controls. The FAP
      patients with L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS) administration
      showed no significant correlation between the degree of OH and the decrease in
      the blood flow of the portal vein, and the patients without the drug exhibited a
      weak correlation. On the contrary, the pandysautonomia and Shy-Drager syndrome
      patients exhibited a linear positive correlation. These results suggest that FAP
      is a disease for which this kind of ultrasonographic examination should be
      applied, and that Doppler ultrasonography may be a helpful tool to evaluate
      visceral OH.

PMID- 9531451
TI  - Segmental origin of sympathetic preganglionic neurones regulating the tail
      circulation in the rat.
AB  - The spinal segments of origin of the sympathetic preganglionic neurones (SPNs)
      influencing the activity of sympathetic postganglionic neurones innervating the
      tail have been studied using a neurophysiological approach. Activity was recorded
      from the ventral collector nerve that carries 70% of the sympathetic fibres
      innervating targets within the tail and provides 80% of the innervation of the
      caudal ventral artery. When recording activity from the ventral collector nerve
      at the tail base, the largest responses were evoked following electrical
      stimulation within spinal segments lumbar (L) 1 and 2 and smaller responses from
      thoracic (T) 13 (n = 5). Although similar responses to those recorded from the
      tail base were elicited from spinal segments L1 and L2, when activity was
      recorded from mid-tail only minimal responses were evoked from T13 (n = 6). On
      average robust responses were never elicited following stimulation beyond these
      segments. Responses had latencies compatible with conduction over C-fibre axons
      and were absent following ganglionic blockade. It is concluded that SPNs
      influencing the tail circulation reside mainly in L1 and L2 spinal segments and
      there is also a substantial but lesser contribution arising from segment T13.

PMID- 9531452
TI  - Cardiorespiratory reflexes in mice.
AB  - The various transgenic strains of mice make this species an attractive
      experimental model. We compared qualitatively some cardiorespiratory reflexes in
      two different preparations of mouse: in vivo urethane anaesthetised and a working
      heart-brainstem preparation (WHBP). Cardiorespiratory reflexes were evoked by
      stimulating baroreceptors, pulmonary vagal C fibres and cardiac receptors in both
      preparations, while peripheral chemoreceptors were also stimulated in the WHBP.
      In anaesthetised mice, activation of baroreceptors, pulmonary C fibres and
      cardiac receptors evoked an atropine-sensitive bradycardia (range: 21-414
      bts/min) and depressed ventilation. A reflex fall in arterial pressure was also
      observed during pulmonary C fibre and cardiac receptor stimulation. Similar
      reflex bradycardia (range 81-164 bts/min) and respiratory responses were observed
      in the WHBP following stimulation of baro-, pulmonary C fibre and cardiac
      receptors. Additionally, sodium cyanide stimulation of peripheral chemoreceptors
      in the WHBP produced an atropine-sensitive bradycardia and increased respiratory
      frequency and amplitude. Thus, the cardiorespiratory reflex responses elicited in
      the mouse are similar to those reported in other species. It is concluded that
      the qualitatively similar reflex performances between the in vivo anaesthetised
      mouse and the WHBP make the latter an adequate model for studying central
      mechanisms controlling the cardiorespiratory system.

PMID- 9531453
TI  - A method for vibratome sectioning of Golgi-Cox stained whole rat brain.
AB  - A method for impregnating the whole rat brain with Golgi-Cox stain and sectioning
      with the vibratome is described. The method is simple, inexpensive and provides
      good resolution of dendrites and spines.

PMID- 9531454
TI  - Rapid apolipoprotein E genotyping from mailed buccal swabs.
AB  - Genetic polymorphism of apolipoprotein E (apoE) is linked with the risk of
      cardiovascular and Alzheimer's disease (AD). We determined apoE genotypes from
      mailed buccal cell swabs in 36 healthy individuals and 18 demented patients
      suffering from AD. DNA was released from the swabs by a rapid lysis technique.
      Polymerase chain reaction using 'hot start' and restriction enzyme digestion by
      HhaI was used for genotyping of apoE alleles, which were detected by
      polyacrylamide or MetaPhor agarose gel. ApoE genotypes determined from buccal
      cells or from stored leucocytes were identical to previously done phenotyping. An
      advantage of the present simplified buccal cell collection procedure is the
      possibility to collect DNA samples for apoE genotyping rapidly by mail from
      patients visiting their physician geographically distant from research
      laboratory. Moreover, venepuncture and storing of the samples in refrigerators
      are avoided and costs are reduced. This non-invasive and painless method is also
      applicable to other genetic screening tests in risk populations.

PMID- 9531455
TI  - Real time measurement of stimulated dopamine release in the conscious rat using
      fast cyclic voltammetry: dopamine release is not observed during intracranial
      self stimulation.
AB  - Fast cyclic voltammetry (FCV) was used to measure real time release of
      electrically stimulated endogenous dopamine in the nucleus accumbens (NAc) of
      conscious freely moving rats for up to 17 days. The method of electrode
      construction, implantation, electrical stimulation and recording of changes of
      extracellular dopamine concentration in the conscious rat are described. Rats
      trained on a continuous reinforcement schedule to perform intracranial self
      stimulation (ICSS) were implanted with electrodes for FCV. During ICSS, no
      faradaic signal was observed at an electrode implanted in the NAc. Decreasing the
      intensity of the stimulating current abolished ICSS, increasing the stimulating
      current disrupted ICSS. Operator delivered electrical stimulations using currents
      greater than those needed for ICSS yielded dopamine signals. It is concluded that
      during ICSS, sufficient dopamine does not reach the extracellular fluid space to
      yield a faradaic signal detectable by FCV.

PMID- 9531456
TI  - A novel approach to identify proteins associated with the inhibition of neurite
      growth.
AB  - In the present study, a novel combination of techniques was used to identify the
      genes that may be involved in the lack of axonal regeneration in the mammalian
      adult central nervous system (CNS). The key features of this approach are: (1) a
      functional assay that can be affected by antibody perturbation; (2) increased
      specificity of the polyclonal antiserum by adsorption; (3) the expression cloning
      of the genes from a lambdagt11 library; (4) amplification of the insert cDNA by
      PCR; and (5) the direct cycle sequencing of PCR products. In this culture assay
      system, neurons were plated directly on sections of the rat CNS. This assay
      system could be used to demonstrate the lack of neuronal attachment to or neurite
      extension over myelinated regions of the CNS (white matter). This prohibitive
      nature of the CNS sections could be masked by a rabbit polyclonal antiserum
      directed against rat CNS white matter. This data indicates that the anti-white
      matter antiserum recognizes and neutralizes inhibitory molecules on the surface
      of the sections. Making the assumption that the prohibitive antigen is associated
      with the cell membrane, the antiserum was adsorbed against a soluble protein
      fraction of the adult rat brain. This adsorption significantly increased the
      specificity of the antiserum as demonstrated by immunoblot methods. The adsorbed
      antiserum was then used to screen the cDNA library of the adult rat brain. The
      present report describes this novel combination of techniques allowing one to go
      from a functional tissue culture assay system to defining the molecular basis for
      the cellular interactions.

PMID- 9531457
TI  - Long-term intracranial cannula stabilization in mice with light cured resin
      composites.
AB  - A simple and rapid method is described for the introduction and stabilization of
      chronic indwelling cannulae in mice. Materials and adhesive bonding techniques
      commonly used in restorative dentistry were used to stabilize the cannulae. The
      effectiveness of this method was evaluated by shear strength testing across time
      and histological evaluation of coronal brain sections. Shear strength increased
      during the first week post surgery and remained stable for up to 60 days. The
      force required to dislodge the cannulae from skulls ranged from 0.70 to 2.45 kg.
      Histological evaluation revealed no significant infection or inflammatory
      response due to the materials used. Cannulae stabilization by this technique
      appears to be suitable for most experimental conditions.

PMID- 9531458
TI  - Electrophysiology of embryonic, adult and aged rat hippocampal neurons in serum
      free culture.
AB  - Methods were recently developed for culturing neurons from adult rat hippocampus
      using the serum-free medium Neurobasal with B27 supplement. To determine whether
      adult cultured neurons have normal electrical properties, we studied cultures
      from rats of three age groups: (1) embryonic; (2) 10-11 months old and (3) 35-36
      months old. Neurons had a polarized morphology with a large branching apical
      dendrite and small basal dendrites. Mean resting potentials were similar in the
      three age groups. All neurons had nonlinear current-voltage relationships,
      indicating the presence of voltage-sensitive ion channels. Most neurons had a
      voltage-sensitive inward current followed by a sustained voltage-sensitive
      outward current. Tetrodotoxin blocked the inward current, which is likely to be a
      sodium current. The sustained outward current, which is likely to be a potassium
      current, reversed at -71 mV. Most neurons exhibited anomalous rectification.
      Calcium currents were present in both embryonic and adult neurons. Embryonic
      neurons would sometimes fire multiple action potentials but adult neurons fired
      only single action potentials. Our results indicate that both embryonic and adult
      cultured neurons retain a clearly neuronal electrophysiological phenotype in
      Neurobasal/B27 serum-free medium.

PMID- 9531459
TI  - The effects of social isolation on the forced swim test in Fawn hooded and Wistar
      rats.
AB  - Although the forced swim test (FST) has long been used as a preclinical screen of
      antidepressant efficacy, locomotor stimulants are known to produce confounding
      effects using the traditional dependent measure in this test: immobility. It has
      recently been suggested that measurement of struggling behavior may be a better
      index of antidepressant activity. The present experiments examined behavior in
      the forced swim test in two potential animal models of depression: the Fawn
      hooded rat, and the isolation-reared rat. No evidence was found to support these
      assertions, indeed immobility was decreased in Fawn hooded compared to Wistar
      rats, however this appeared to be caused by increased struggling behavior in Fawn
      hooded socials and increased swimming in Fawn hooded isolates. Although these
      differential results are highly suggestive of different underlying causes of
      decreased immobility in Fawn hooded rats depending on rearing conditions, the
      data suggests that the underlying psychological functions assumed to be
      represented by behavior assessed in this paradigm may not be adequately
      discriminated.

PMID- 9531460
TI  - A simple procedure for morphometric analysis of processes and growth cones of
      neurons in culture using parameters derived from the contour and convex hull of
      the object.
AB  - Morphometric estimation of neuronal processes is currently laborious and time
      consuming, since the individual processes (axons and dendrites) have to be traced
      manually. In order to facilitate the measurement of cellular processes, we have
      tested a series of parameters derived from the contour and the convex hull of an
      object and estimated to which extent they reflect process length and number. The
      parameters included the area, perimeter and form factor of the object and convex
      hull, their ratios as well as object length, breadth, width, length/width and
      spreading index. Some new parameters derived from the contour and convex hull of
      the object, were also computed: process index (the number of areas contained
      within the convex hull outside the object contour), process domain (the total
      area contained within the convex hull outside the object contour), their ratio
      and the square root of the process domain (SR process domain). In total, 18
      parameters were estimated. Populations of motoneurons, growth cones of cerebellar
      granule cells and N2a neuroblastoma cells were utilized due to their diversity in
      morphological features. The processes of each object were drawn by hand to
      establish the actual length and number. Total process length per object
      correlated strongly with object perimeter, process domain and SR process domain.
      The number of processes per object correlated well with perimeter ratio, process
      index and form factor, whereas object length, convex hull perimeter and spreading
      index correlated acceptably with the average process length. Using these
      parameters for the evaluation of neurite outgrowth in developing of hippocampal
      neurons in vitro, variables such as object perimeter, process domain and SR
      process domain were found to be very well suited for estimation of the total
      length of neurites. We conclude that based on the contour and convex hull of an
      object it is possible to calculate a series of parameters which may substitute
      direct measurements of process length.

PMID- 9531461
TI  - An amperometric glucose-oxidase/poly(o-phenylenediamine) biosensor for monitoring
      brain extracellular glucose: in vivo characterisation in the striatum of freely
      moving rats.
AB  - Amperometric glucose biosensors based on the immobilization of glucose oxidase
      (GOx) on Pt electrodes with electropolymerized o-phenylenediamine (PPD) were
      implanted in the right striatum of freely-moving rats. Carbon paste electrodes
      for the simultaneous monitoring of ascorbic acid (AA) and/or tissue O2 were
      implanted in the left striatum. A detailed in vivo characterization of the
      Pt/PPD/GOx signal was carried out using various pharmacological manipulations.
      Confirmation that the biosensor responded to changing glucose levels in brain
      extracellular fluid (ECF) was obtained by intraperitoneal (i.p.) injection of
      insulin that caused a decrease in the Pt/PPD/GOx current, and local
      administration of glucose (1 mM) via an adjacent microdialysis probe that
      resulted in an increase in the biosensor current. An insulin induced increase in
      tissue O2 in the brain was also observed. Interference studies involved
      administering AA and subanaesthetic doses of ketamine i.p. Both resulted in
      increased extracellular AA levels with ketamine also causing an increase in O2.
      No significant change in the Pt/PPD/GOx current was observed in either case
      indicating that changes in O2 and AA, the principal endogenous interferents, have
      minimal effect on the response of these first generation biosensors. Stability
      tests over a successive 5-day period revealed no significant change in
      sensitivity. These in vivo results suggest reliable glucose monitoring in brain
      ECF.

PMID- 9531463
TI  - A stimulator with wireless power and signal transmission for implantation in
      animal experiments and other applications.
AB  - Functional electrical stimulation in alert experimental animals is often
      hampered, as free mobility of the animals is limited by the leads. On the other
      hand, portable devices carrying the power supply are not always accepted by the
      animal. For wireless transmission of power and stimulus code a system designed
      for implantation is described below. The power for the implant is supplied
      inductively by a rotating magnetic field. The stimulation signal is radio
      transmitted by FM in the 140 MHz range and processed by the implant. Finally, a
      current source is driven for electrical stimulation. The present design is
      intended to be used for electrical cochlear stimulation. However, the circuit can
      also be used for other types of functional electrical stimulation.

PMID- 9531462
TI  - Axonal transport of herpes simplex virus-1 in an in vitro model based on the
      isolated sciatic nerve of the frog Rana ridibunda.
AB  - An in vitro model for the study of the axonal transport of herpes simplex virus-1
      (HSV-1) in the nerve fibres of the sciatic nerve of the frog Rana ridibunda, has
      been developed. The nerve was placed along a three-chambered bath consisting of
      three isolated chambers arranged in series: the stimulating, perfusion and
      recording chambers. The HSV-1 inoculum was placed in the stimulating chamber,
      where the proximal part of the isolated sciatic nerve was immersed. HSV-1 was
      detected after 24-36 h in the recording chamber, where the distal part of the
      nerve was immersed in Dulbecco's Modified Eagle Medium (DMEM), indicating an
      axonal transport speed of 46-60 mm/day. The evoked maximum compound action
      potentials generated in the stimulating chamber was monitored continuously in the
      recording chamber as an indication of the viability of the nerve during axonal
      transport. The in vitro method presented here is a useful tool for the
      pharmacological study of various parameters, e.g. drugs diluted in the perfusion
      chamber, ionising radiation and temperature, which may affect the axonal
      transport or other properties of HSV-1.

PMID- 9531464
TI  - A simplified procedure for the physical development of the sulphide silver method
      to reveal synaptic zinc in combination with immunocytochemistry at light and
      electron microscopy.
AB  - The pool of zinc present in excitatory synaptic terminals in normal and
      pathological conditions (for instance the status epilepticus induced by kainic
      acid) can be stained by a silver sulphide method followed by physical development
      of the insoluble zinc-sulphide complexes. In this study we applied a previously
      described simple and rapid developing procedure that reveals synaptic zinc, to
      the study of normal and pathological hippocampi and combined it with pre and
      postembedding immunocytochemical methods to detect different antigens. Normal and
      kainic acid-treated rats were perfused with fixative solutions containing sodium
      sulphide and 50 microm-thick vibratome sections of the hippocampi were incubated
      in a commercial developing solution (IntenSE M, Amersham). The developed
      vibratome sections were then (1) mounted for light microscopy or osmicated and
      epon-embedded for electron microscopy; or (2) processed for the preembedding
      immunoenzymatic detection of various antigens (GABA, parvalbumin, calbindin) with
      light and electron microscopy. Thin sections from epon-embedded samples were also
      processed for the postembedding immunogold localization of glutamate. This very
      simple and rapid procedure gives rise to zinc-specific staining, comparable to
      that obtained with classical developing methods and good preservation of both
      antigenicity and ultrastructure. It is therefore possible to detect, in the same
      thick or thin section, zinc reaction product and different antigens.

PMID- 9531465
TI  - Patch clamp recording from the intact dorsal root ganglion.
AB  - A method for patch-clamp recording from intact dorsal root ganglion (DRG) cells
      in rat is described. The L4 and L5 DRGs with sciatic nerve attached were excised
      from rats (10-15 days old) and placed in a recording chamber after removing the
      ganglion sheath and dissolving the connective tissue with dilute collagenase. The
      somata of individual cells were exposed by gentle surface cleaning through a
      perfusion micropipette. Somata were classified as Abeta, Adelta or C based on the
      cell size and the shape of the action potential (AP). Under current clamp, axonal
      conduction velocity (CV) was calculated from the distance between a stimulating
      electrode and the center of the ganglion divided by the latency of the AP
      elicited by stimulation of the sciatic nerve. CVs ranged from 0.2-0.8 m/s for C
      cells, 0.8-2.4 for Adelta and 3.2-5.0 for A/beta cells. AP threshold occurred at
      a significantly more positive potential in C cells than in Adelta and Abeta
      cells. Under voltage clamp, sodium currents were recorded from C cells. Both TTX
      resistant (TTX-R) and TTX-sensitive (TTX-S currents) were demonstrated in the
      present study. The results demonstrate the feasibility of patch-clamp recording
      from intact, identified DRG cells in vitro.

PMID- 9531466
TI  - c-fos expression in isolated rat spinal cord.
AB  - Expression of c-fos-immunoreactivity (c-fos-ir) has been demonstrated in the
      dorsal horn of lumbar segments of an isolated spinal cord preparation from 3 week
      old rats. The method of preparation generated a low level of c-fos-ir activity
      which was not significantly altered by low intensity (1.5 times threshold) dorsal
      root stimulation, but was significantly increased by high intensity (20 times
      threshold) stimulation. Replacement of the calcium in the bathing medium by 2 mM
      manganese suppressed all detectable c-fos-ir, whereas inclusion of 0.5 microM
      capsaicin caused intense c-fos-ir expression in the absence of stimulation. The
      number of dorsal horn cells exhibiting c-fos-ir increased between 0.5 and 1 h
      after stimulation, reaching a maximum at 2 h, with no further increase at longer
      intervals. Few positive cells were found when the incubation temperature was
      reduced from 27 to 20 degrees C. The strongest increase in c-fos-ir was found in
      the dorsal horn ipsilateral to the stimulated dorsal root and a smaller, but
      significant, increase was also seen in the contralateral dorsal horn. Cords
      obtained from animals treated at 1 day old with capsaicin to destroy afferent C
      fibres showed a reduction in the number of c-fos-ir positive cells induced by
      high intensity dorsal root stimulation. This preparation will aid detailed
      investigation of the pharmacology of nociceptive pathways.

PMID- 9531468
TI  - A low-cost, multi-channel, EMG signal processing amplifier.
AB  - There is a growing need in studies of movement control to expand the number of
      muscles from which EMG activity is recorded during performance of motor tasks.
      Optimal viewing and analysis of this EMG activity requires signal processing
      which provides adjustable gain and baseline offset as wells as selectable AC
      coupling, rectification and filtering. This paper presents a low-cost circuit
      that combines two channels of EMG signal processing capability in one module.

PMID- 9531467
TI  - Changes in blood-brain barrier permeability following neurotoxic lesions of rat
      brain can be visualised with trypan blue.
AB  - A simple method for measuring changes in blood-brain barrier (BBB) permeability
      following neurotoxic lesions is described. In the brains of animals perfused
      transcardially with a trypan blue solution at the time of sacrifice, the presence
      of trypan blue staining correlated with changes in BBB function seen with more
      traditional markers, such as albumin staining. Thus, trypan blue appears to be
      useful as a marker for changes in BBB permeability. We have used this method to
      show increases in BBB permeability in striatal lesions induced by three different
      neurotoxins: chronic systemic injection of 3-nitropropionic acid (3-NP) and
      intrastriatal injection of either quinolinic or kainic acid. Trypan blue staining
      was seen in all three types of lesion, with both the neuropil and some neurones
      being stained. In the kainic acid lesioned animals, trypan blue also stained
      hippocampal and cortical neurones which are known to degenerate. Our findings
      suggest that trypan blue makes a more sensitive marker than albumin for both BBB
      integrity changes and degenerating neurones. Furthermore, this method has the
      advantages over others of being quick, economic and compatible with most
      subsequent histological and immunocytochemical staining.

PMID- 9531469
TI  - Bacterial expression and characterization of human secretory class V
      phospholipase A2.
AB  - Mammalian secretory class V phospholipase A2 (PLA2) is a newly discovered PLA2
      that is implicated in eicosanoid formation in inflammatory cells. As a first step
      towards understanding the structure, function and regulation of this PLA2, we
      constructed a bacterial expression vector for human secretory class V PLA2 (hV
      PLA2), over-expressed and purified the protein, and determined its physical and
      kinetic properties. When compared with human class IIa enzyme (hIIa-PLA2), hV
      PLA2 has several distinct properties. First, hV-PLA2 can catalyse the hydrolysis
      of phosphatidylcholine more effectively than hIIa-PLA2 by two orders of
      magnitude. Secondly, hV-PLA2 has much higher binding affinity and activity for
      compactly packed phosphatidylcholine bilayers than hIIa-PLA2. Finally, hV-PLA2
      has much reduced thermal stability compared with hIIa-PLA2. These data suggest
      that hV-PLA2 is better suited than hIIa-PLA2 for acting on the outer cellular
      membrane and liberating arachidonic acid from membrane phospholipids. Also, the
      unusually low thermal stability of hV-PLA2 might contribute to tighter regulation
      of its activities in extracellular media.

PMID- 9531470
TI  - Cloning of a functional promoter of the human sodium/iodide-symporter gene.
AB  - We have cloned and sequenced genomic DNA from a human library extending 1300 bp
      upstream the 5'-untranslated sequence of the cDNA coding for the sodium/iodide
      symporter. In transient transfection assays this sequence exhibited promoter
      activity, which could be confined to nucleotides -443 to -395 relative to the ATG
      start codon. This minimal promoter, including a putative GC- and TATA- box, was
      preferentially activated in the rat thyroid cell line FRTL-5, but was also active
      in non-thyroidal cells, such as COS-7 and Chinese-hamster ovary, albeit to a
      markedly lower extent.

PMID- 9531471
TI  - Measurement of oxidative DNA damage by gas chromatography-mass spectrometry:
      ethanethiol prevents artifactual generation of oxidized DNA bases.
AB  - Analysis of oxidative damage to DNA bases by GC-MS enables identification of a
      range of base oxidation products, but requires a derivatization procedure.
      However, derivatization at high temperature in the presence of air can cause
      'artifactual' oxidation of some undamaged bases, leading to an overestimation of
      their oxidation products, including 8-hydroxyguanine. Therefore derivatization
      conditions that could minimize this problem were investigated. Decreasing
      derivatization temperature to 23 degrees C lowered levels of 8-hydroxyguanine, 8
      hydroxyadenine, 5-hydroxycytosine and 5-(hydroxymethyl)uracil measured by GC-MS
      in hydrolysed calf thymus DNA. Addition of the reducing agent ethanethiol (5%,
      v/v) to DNA samples during trimethylsilylation at 90 degrees C also decreased
      levels of these four oxidized DNA bases as well as 5-hydroxyuracil. Removal of
      guanine from hydrolysed DNA samples by treatment with guanase, prior to
      derivatization, resulted in 8-hydroxyguanine levels (54-59 pmol/mg of DNA) that
      were significantly lower than samples not pretreated with guanase, independent of
      the derivatization conditions used. Only hydrolysed DNA samples that were
      derivatized at 23 degrees C in the presence of ethanethiol produced 8
      hydroxyguanine levels (56+/-8 pmol/mg of DNA) that were as low as those of
      guanase-pretreated samples. Levels of other oxidized bases were similar to
      samples derivatized at 23 degrees C without ethanethiol, except for 5
      hydroxycytosine and 5-hydroxyuracil, which were further decreased by ethanethiol.
      Levels of 8-hydroxyguanine, 8-hydroxyadenine and 5-hydroxycytosine measured in
      hydrolysed calf thymus DNA by the improved procedures described here were
      comparable with those reported previously by HPLC with electrochemical detection
      and by GC-MS with prepurification to remove undamaged base. We conclude that
      artifactual oxidation of DNA bases during derivatization can be prevented by
      decreasing the temperature to 23 degrees C, removing air from the derivatization
      reaction and adding ethanethiol.

PMID- 9531472
TI  - Glutathione transferase zeta catalyses the oxygenation of the carcinogen
      dichloroacetic acid to glyoxylic acid.
AB  - Dichloroacetic acid (DCA), a common drinking-water contaminant, is
      hepatocarcinogenic in rats and mice, and is a therapeutic agent used clinically
      in the management of lactic acidosis. DCA is biotransformed to glyoxylic acid by
      glutathione-dependent cytosolic enzymes in vitro and is metabolized to glyoxylic
      acid in vivo. The enzymes that catalyse the oxygenation of DCA to glyoxylic acid
      have not, however, been identified or characterized. In the present
      investigation, an enzyme that catalyses the glutathione-dependent oxygenation of
      DCA was purified to homogeneity (587-fold) from rat liver cytosol. SDS/PAGE and
      HPLC gel-filtration chromatography showed that the purified enzyme had a
      molecular mass of 27-28 kDa. Sequence analysis showed that the N-terminus of the
      purified protein was blocked. An internal sequence of 30 amino acid residues was
      obtained that matched the recently discovered human glutathione transferase Zeta
      well [Board, Baker, Chelvanayagam and Jermiin (1997) Biochem. J. 328, 929-935].
      Western-blot analysis showed that the purified rat-liver enzyme cross-reacted
      with rabbit antiserum raised against recombinant human glutathione transferase
      Zeta. The apparent Km and Vmax values of the purified enzyme with DCA as the
      variable substrate were 71.4 microM and 1334 nmol/min per mg of protein,
      respectively; the Km for glutathione was 59 microM. Both the purified rat-liver
      enzyme and the recombinant human enzyme showed high activity with DCA as the
      substrate. These results demonstrate that the glutathione-dependent oxygenation
      of DCA to glyoxylic acid is catalysed by a Zeta-class glutathione transferase.

PMID- 9531473
TI  - Phosphinic peptides, the first potent inhibitors of astacin, behave as extremely
      slow-binding inhibitors.
AB  - A series of phosphinic pseudo-peptides varying in length and composition have
      been designed as inhibitors of the crayfish zinc endopeptidase astacin, the
      prototype of the astacin family and of the metzincin superfamily of
      metalloproteinases. The most efficient phosphinic peptide,
      fluorenylmethyloxycarbonyl-Pro-Lys-PhePsi(PO2CH2)Ala-P ro-Leu-Val, binds to
      astacin with a Ki value of 42 nM, which is about three orders of magnitude below
      the corresponding values for previously used hydroxamic acid derivatives.
      However, the rate constants for association (kon = 96.8 M-1.s-1) and dissociation
      (koff = 4.1 x 10(-6) s-1) are evidence for the extremely slow binding behaviour
      of this compound. N-terminally or C-terminally truncated phosphinic analogues of
      this parent molecule are much less potent, indicating a critical role of the
      peptide size on the potency. In particular, omission of the N-terminal proline
      residue leads to a 40-fold increase in Ki which is mostly due to a 75-fold higher
      koff value. These findings are consistent with the previously solved crystal
      structure of astacin complexed with one of the phosphinic peptides,
      benzyloxycarbonyl-Pro-Lys-PhePsi(PO2CH2)Ala-Pro-O-methyl, Ki = 14 microM [Grams,
      Dive, Yiotakis, Yiallouros, Vassiliou, Zwilling, Bode and Stocker (1996) Nature
      Struct. Biol. 3, 671-675]. This structure also reveals that the phosphinic group
      binds to the active site as a transition-state analogue. The extremely slow
      binding behaviour of the phosphinic peptides is discussed in the light of the
      conformational changes involving a unique 'tyrosine switch' in the structure of
      astacin upon inhibitor binding. The phosphinic peptides may provide a rational
      basis for the design of drugs directed towards other members of the astacin
      family which, like bone morphogenetic protein 1 (BMP1; i.e. the procollagen C
      proteinase), have become targets of pharmacological research.

PMID- 9531474
TI  - Expression of v-src in mammary epithelial cells induces transcription via STAT3.
AB  - Transgenic mouse models of mammary tumorigenesis and analyses of human breast
      tumour samples have indicated a role for Src proteins in the tumorigenic process.
      The downstream effectors of Src function in mammary epithelial cells are less
      well understood. STAT proteins constitute a family of transcription factors whose
      activation by cytokine and non-cytokine receptors leads to tyrosine
      phosphorylation, dimerization and translocation from the cytoplasm to the
      nucleus. In the nucleus they activate the transcription of specific genes by
      binding to consensus DNA elements. STATs 1 and 3 can be activated by both
      cytokine and non-cytokine receptors, and bind as homodimers or heterodimers to
      viral simian sarcoma virus (sis)-inducible elements such as that found in the c
      fos promoter. Here we report that one of the downstream effectors of Src function
      in mammary epithelial cells is STAT3. We demonstrate that v-src expression in
      mammary epithelial cells induces Tyr-705 phosphorylation, nuclear translocation
      and DNA binding of STAT3. Furthermore, we demonstrate that v-src can induce STAT3
      dependent transcription. These observations are the first direct evidence that v
      src can regulate transcription through the activation of STAT proteins, and add a
      further level of complexity to the understanding of the mode of action of v-src.

PMID- 9531475
TI  - Nucleolar protein p120 contains an arginine-rich domain that binds to ribosomal
      RNA.
AB  - Human proliferation-associated protein p120 has previously been shown to localize
      to the nucleolus, and several functional domains of p120 have been elucidated. By
      using a nitrocellulose filter binding assay and a Northwestern blotting procedure
      this study shows that recombinant p120 binds to an rRNA fragment in vitro with a
      dissociation constant of 4 nM. The specific RNA-binding region of p120 (residues
      1-57) was identified with glutathione S-transferase-fused p120 deletion
      constructs and Northwestern blotting procedures. This RNA-binding region of p120,
      which includes the nucleolar localization signal of p120, is similar to the
      arginine-rich RNA-binding regions found in other RNA-binding proteins such as HIV
      Rev and Tat. Experiments in vivo with HeLa cell nucleolar extracts showed that
      p120 was associated with the 60-80S pre-ribosomal particles. This association is
      disrupted by treatment with either RNase A or buffer of high ionic strength.
      These results suggest that p120 might be involved in rRNA/ribosome maturation,
      consistent with the role of the yeast homologue Nop2p in rRNA biogenesis.

PMID- 9531476
TI  - Subunit interaction of vacuolar H+-pyrophosphatase as determined by high
      hydrostatic pressure.
AB  - Vacuolar H+-pyrophosphatase (H+-PPase) from etiolated hypocotyls of mung bean
      (Vigna radiata L.) is a homodimer with a molecular mass of 145 kDa. The vacuolar
      H+-PPase was subjected to high hydrostatic pressure to investigate its structure
      and function. The inhibition of H+-PPase activity by high hydrostatic pressure
      has a pressure-, time- and protein-concentration-dependent manner. The Vmax value
      of vacuolar H+-PPase was dramatically decreased by pressurization from 293.9 to
      70.2 micromol of PPi (pyrophosphate) consumed/h per mg of protein, while the Km
      value decreased from 0.35 to 0.08 mM, implying that the pressure treatment
      increased the affinity of PPi to vacuolar H+-PPase but decreased its hydrolysis.
      The physiological substrate and its analogues enhance high pressure inhibition of
      vacuolar H+-PPase. The HPLC profile reveals high pressure treatment of H+-PPase
      provokes the subunit dissociation from an active into inactive form. High
      hydrostatic pressure also induces the conformational change of vacuolar H+-PPase
      as determined by spectroscopic techniques. Our results indicate the importance of
      protein-protein interaction for this novel proton-translocating enzyme. Working
      models are proposed to interpret the pressure inactivation of vacuolar H+-PPase.
      We also suggest that association of identical subunits of vacuolar H+-PPase is
      not random but proceeds in a specific manner.

PMID- 9531477
TI  - pH-dependent inhibition by azide and fluoride of the iron superoxide dismutase
      from Propionibacterium shermanii.
AB  - The iron-containing superoxide dismutase from Propionibacterium shermanii shows,
      in contrast with other iron superoxide dismutases, only a minor inhibition by
      azide or fluoride (10-100 mM) of up to 23% at pH 7.8. The activity of the protein
      with Mn bound to the active site was not diminished under the same conditions.
      The binding constant between azide and the Fe3+ ion was determined as approx. 2
      mM and for fluoride approx. 2.3 mM; they are so far comparable to those known for
      other iron superoxide dismutases. This seems to be a discrepancy because all
      other iron superoxide dismutases so far known are described as being inhibited by
      50-70% by 10 mM azide. However, towards lower pH there was a drastically
      increased inhibition by both anions. At pH 6.8 about 80% inhibition was exhibited
      by azide or fluoride at a concentration of 10 mM or higher. In contrast, on
      increasing the pH, azide or fluoride still bound to the Fe3+ at the active site
      but their inhibition capacity decreased. This observation implies that both
      anions bind to the metal at a position that is empty at low pH, whereas at higher
      pH water or a negatively charged hydroxyl anion is bound. It is likely that the
      superoxide anion binds to the same position and has to replace the sixth ligand,
      leading to a diminished catalytic activity of the superoxide dismutase owing to
      steric and/or electrostatic inhibition of the ligand.

PMID- 9531478
TI  - Functional effects of single amino acid substitutions in the region of Phe113 to
      Asp138 in the plasminogen activator inhibitor 1 molecule.
AB  - Thirteen amino acid substitutions have been introduced within the stretch Phe113
      to Asp138 in the plasminogen activator inhibitor 1 (PAI-1) molecule by site
      directed mutagenesis. The different proteins and wild-type (wt) PAI-1 have been
      overexpressed in Escherichia coli and purified by chromatography on heparin
      Sepharose and on anhydrotrypsin-agarose. The PAI-1 variants have been
      characterized by their reactivity with tissue plasminogen activator (tPA),
      interactions with vitronectin or heparin, and stability. Most PAI-1 variants,
      except for Asp125-->Lys, Phe126-->Ser and Arg133-->Asp, displayed a high
      spontaneous inhibitory activity towards tPA, which did not change greatly on
      reactivation with 4 M guanidinium chloride, followed by dialysis at pH 5.5. The
      variants Asp125-->Lys and Arg133-->Asp became much more active after reactivation
      and they were also more rapidly transformed to inactive forms (t12 22-31 min) at
      physiological pH and temperature than the other variants. However, in the
      presence of vitronectin they were both almost equally stable (t12 2.3 h) as wtPAI
      1 (t12 3.0 h). The mutant Glu130-->Lys showed an increased stability, both in the
      absence and in the presence of vitronectin compared with wtPAI-1. Nevertheless a
      similar affinity between all the active PAI-1 variants and vitronectin was
      observed. Further, all mutants, including the three mutants with low activity,
      were to a large extent adsorbed on anhydrotrypsin-agarose and were eluted in a
      similar fashion. In accordance with these data, the three variants with a low
      activity were all to a large extent cleaved as a result of their reaction with
      tPA, suggesting that they occurred predominantly in the substrate conformation.
      Our results do not support the presence of a binding site for vitronectin in this
      part of the molecule, but rather that it might be involved in controlling the
      active PAI-1 to substrate transition. Partly, this region of the PAI-1 molecule
      (Arg115 to Arg118) seems also to be involved in the binding of heparin to PAI-1.

PMID- 9531479
TI  - Regulation of type I collagen mRNA in lung fibroblasts by cystine availability.
AB  - The steady-state level of alpha1(I) collagen mRNA is regulated by amino acid
      availability in human lung fibroblasts. Depletion of amino acids decreases
      alpha1(I) collagen mRNA levels and repletion of amino acids induces rapid re
      expression of alpha1(I) mRNA. In these studies, we examined the requirements for
      individual amino acids on the regulation of alpha1(I) collagen mRNA. We found
      that re-expression of alpha1(I) collagen mRNA was critically dependent on cystine
      but not on other amino acids. However, the addition of cystine alone did not
      result in re-expression of alpha1(I) collagen mRNA. Following amino acid
      depletion, the addition of cystine with selective amino acids increased alpha1(I)
      collagen mRNA levels. The combination of glutamine and cystine increased
      alpha1(I) collagen mRNA levels 6.3-fold. Methionine or a branch-chain amino acid
      (leucine, isoleucine or valine) also acted in combination with cystine to
      increase alpha1(I) collagen mRNA expression, whereas other amino acids were not
      effective. The prolonged absence of cystine lowered steady-state levels of
      alpha1(I) collagen mRNA through a mechanism involving decreases in both the rate
      of gene transcription as assessed by nuclear run-on experiments and mRNA
      stability as assessed by half-life determination in the presence of actinomycin
      D. The effect of cystine was not mediated via alterations in the level of
      glutathione, the major redox buffer in cells, as determined by the addition of
      buthionine sulphoximine, an inhibitor of gamma-glutamylcysteine synthetase. These
      data suggest that cystine directly affects the regulation of alpha1(I) collagen
      mRNA.

PMID- 9531480
TI  - Functional implications of ribosomal protein L2 in protein biosynthesis as shown
      by in vivo replacement studies.
AB  - The translational apparatus is a highly complex structure containing three to
      four RNA molecules and more than 50 different proteins. In recent years
      considerable evidence has accumulated to indicate that the RNA participates
      intensively in the catalysis of peptide-bond formation, whereas a direct
      involvement of the ribosomal proteins has yet to be demonstrated. Here we report
      the functional and structural conservation of a peptidyltransferase centre
      protein in all three phylogenetic domains. In vivo replacement studies show that
      the Escherichia coli L2 protein can be replaced by its homologous proteins from
      human and archaebacterial ribosomes. These hybrid ribosomes are active in protein
      biosynthesis, as proven by polysome analysis and poly(U)-dependent
      polyphenylalanine synthesis. Furthermore, we demonstrate that a specific, highly
      conserved, histidine residue in the C-terminal region of L2 is essential for the
      function of the translational apparatus. Replacement of this histidine residue in
      the human and archaebacterial proteins by glycine, arginine or alanine had no
      effect on ribosome assembly, but strongly reduced the translational activity of
      ribosomes containing these mutants.

PMID- 9531481
TI  - cADP-ribose formation by blood platelets is not responsible for intracellular
      calcium mobilization.
AB  - Human platelet CD38 is a multifunctional ectoenzyme catalysing the synthesis and
      hydrolysis of cADP-ribose (cADPR), a recently identified calcium-mobilizing agent
      that acts independently of D-myo-inositol 1,4,5-trisphosphate and is known to be
      expressed by human platelets. The present work shows that ADP-ribosyl cyclase
      activity is exclusively a membrane activity, of which the major part is located
      in plasma membranes and a small part in internal membranes. In broken cells,
      cyclase activity was insensitive to the presence of calcium and was not modulated
      by agonists such as thrombin or ADP, whereas in intact cells thrombin increased
      cADPR formation by 30%, an effect due to fusion of granules with the plasma
      membrane. In order to assess the role of cADPR as a calcium-mobilizing agent,
      vesicles were prepared from internal membranes and loaded with 45CaCl2. These
      vesicles were efficiently discharged by IP3 in a dose-dependent manner, but were
      not responsive to cADPR or ryanodine in the presence or absence of calmodulin.
      Thus cADPR is unlikely to play a role in intracellular calcium release in human
      blood platelets.

PMID- 9531482
TI  - The dhnA gene of Escherichia coli encodes a class I fructose bisphosphate
      aldolase.
AB  - The gene encoding the Escherichia coli Class I fructose-1, 6-bisphosphate
      aldolase (FBP aldolase) has been cloned and the protein overproduced in high
      amounts. This gene sequence has previously been identified as encoding an E. coli
      dehydrin in the GenBanktrade mark database [gene dhnA; entry code U73760; Close
      and Choi (1996) Submission to GenBanktrade mark]. However, the purified protein
      overproduced from the dhnA gene shares all its properties with those known for
      the E. coli Class I FBP aldolase. The protein is an 8-10-mer with a native
      molecular mass of approx. 340 kDa, each subunit consisting of 349 amino acids.
      The Class I enzyme shows low sequence identity with other known FBP aldolases,
      both Class I and Class II (in the order of 20%), which may be reflected by some
      novel properties of this FBP aldolase. The active-site peptide has been isolated
      and the Schiff-base-forming lysine residue (Lys236) has been identified by a
      combination of site-directed mutagenesis, kinetics and electrospray-ionization
      MS. A second lysine residue (Lys238) has been implicated in substrate binding.
      The cloning of this gene and the high levels of overexpression obtained will
      facilitate future structure-function studies.

PMID- 9531483
TI  - Cloning and characterization of a novel sequence-specific single-stranded-DNA
      binding protein.
AB  - The promoter region of the chicken alpha2(I) collagen gene contains a pyrimidine
      rich element that is well conserved in different mammalian species. This sequence
      can also form an unusual DNA structure as shown by its sensitivity to SI nuclease
      in vitro and it lies in a region that is DNase I-hypersensitive only when this
      promoter is active. We have recently reported that fibroblast nuclear proteins,
      including chicken Y-box-binding protein 1, bind to this single-stranded
      pyrimidine-rich sequence. Here we report the isolation, from a chick embryo
      fibroblast cDNA expression library, of a partial cDNA clone encoding a previously
      unknown protein, designated SSDP (sequence-specific single-stranded DNA-binding
      protein), that binds this single-stranded sequence. This clone contains 1199 bp
      of chicken sequence and has a single long open reading frame that encodes 284
      amino acid residues. The affinity-purified recombinant protein encoded by this
      cDNA binds sequence-specifically to the single-stranded pyrimidine sequence. This
      cDNA sequence lacks significant similarity to any known gene in the data banks,
      but it is highly conserved in expressed sequence tags derived from both mouse and
      human. The corresponding amino acid sequence is remarkably conserved, having 97%
      identity with mouse and human expressed sequences. The corresponding mRNA is
      approx. 1800 nt in length and is expressed in both fibroblasts and chondrocytes.
      The high affinity of this protein for this conserved pyrimidine-rich region
      suggests that it might be involved in the transcriptional regulation of the
      alpha2(I) collagen gene.

PMID- 9531485
TI  - The reaction of halides with pulsed cytochrome bo from Escherichia coli.
AB  - Cytochrome bo forms complexes with chloride, bromide and iodide in which haem o
      remains high-spin and in which the '630 nm' charge-transfer band is red-shifted
      by 7-8 nm. The chloride and bromide complexes each have a characteristic set of
      integer-spin EPR signals arising from spin coupling between haem o and CuB. The
      rate and extent of chloride binding decreases as the pH increases from 5.5 to
      8.5. At pH 5.5 the dissociation constant for chloride is 2 mM and the first-order
      rate constant for dissociation is 2 x 10(-4) s-1. The order of rate of binding,
      and of affinity, at pH 5.5 is chloride (1) > bromide (0.3) >iodide (0.1). It is
      suggested that the halides bind in the binuclear site but, unlike fluoride, they
      are not direct ligands of the iron of haem o. In addition, both the stability of
      the halide complexes and the rate of halide binding seem to be increased by the
      co-binding of a proton.

PMID- 9531484
TI  - Induction of matrix metalloproteinase activation cascades based on membrane-type
      1 matrix metalloproteinase: associated activation of gelatinase A, gelatinase B
      and collagenase 3.
AB  - SW1353 chondrosarcoma cells cultured in the presence of interleukin-1,
      concanavalin A or PMA secreted procollagenase 3 (matrix metalloproteinase-13).
      The enzyme was detected in the culture medium by Western blotting using a
      specific polyclonal antibody raised against recombinant human procollagenase 3.
      Oncostatin M enhanced the interleukin-1-induced production of procollagenase 3,
      whereas interleukin-4 decreased procollagenase 3 synthesis. The enzyme was latent
      except when the cells had been treated with concanavalin A, when a processed form
      of 48 kDa, which corresponds to the active form, was found in the culture medium
      and collagenolytic activity was detected by degradation of 14C-labelled type I
      collagen. The concanavalin A-induced activation of procollagenase 3 coincided
      with the processing of progelatinase A (matrix metalloproteinase-2) by the cells,
      as measured by gelatin zymography. In addition, progelatinase B (matrix
      metalloproteinase-9) was activated when gelatinase A and collagenase 3 were in
      their active forms. Concanavalin A treatment of SW1353 cells increased the amount
      of membrane-type-1 matrix metalloproteinase protein in the cell membranes,
      suggesting that this membrane-bound enzyme participates in an activation cascade
      involving collagenase 3 and the gelatinases. This cascade was effectively
      inhibited by tissue inhibitors of metalloproteinases-2 and -3. Tissue inhibitor
      of metalloproteinases-1, which is a much weaker inhibitor of membrane-type 1
      matrix metalloproteinase than tissue inhibitors of metalloproteinases-2 and -3
      [Will, Atkinson, Butler, Smith and Murphy (1996) J. Biol. Chem. 271, 17119
      17123], was a weaker inhibitor of the activation cascade.

PMID- 9531486
TI  - The negative charge of glutamic acid-820 in the gastric H+,K+-ATPase alpha
      subunit is essential for K+ activation of the enzyme activity.
AB  - To investigate the role of Glu820, located in transmembrane domain M6 of the
      alpha-subunit of gastric H+,K+-ATPase, a number of mutants was prepared and
      expressed in Sf9 cells using a baculovirus encoding for both H+,K+-ATPase
      subunits. The wild-type enzyme and the E820D (Glu820-->Asp) mutant showed a
      similar biphasic activation by K+ on the ATPase activity (maximum at 1 mM). The
      mutant E820A had a markedly decreased K+ affinity (maximum at 40-100 mM). The
      other mutants, E820Q, E820N, E820L and E820K, showed no K+-activated ATPase
      activity at all, whereas all mutants formed a phosphorylated intermediate. After
      preincubation with K+ before phosphorylation mutant E820D showed a similar K+
      sensitivity as the wild-type enzyme. The mutants E820N and E820Q had a 10-20
      times lower sensitivity, whereas the other three mutants were hardly sensitive
      towards K+. Upon preincubation with 3-(cyanomethyl)-2-methyl-8-(phenylmethoxy)
      imidazo [1,2a]-pyridine (SCH28080), all mutants showed similar sensitivity for
      this drug as the wild-type enzyme, except mutant E820Q, which could only partly
      be inhibited, and mutant E820K, which was completely insensitive towards
      SCH28080. These experiments suggest that, with a relatively large residue at
      position 820, the binding of SCH28080 is obstructed. The various mutants showed a
      behaviour in K+-stimulated-dephosphorylation experiments similar to that for K+
      activated-ATPase-activity measurements. These results indicate that K+ binding,
      and indirectly the transition to the E2 form, is only fully possible when a
      negatively charged residue is present at position 820 in the alpha-subunit.

PMID- 9531487
TI  - Pyrazole-inducible proteins in DBA/2 mouse liver bind with high affinity to the
      3'-untranslated regions of the mRNAs of coumarin hydroxylase (CYP2A5) and c-jun.
AB  - An important mechanism in the up-regulation of cytochrome P-450 2A5 (CYP2A5,
      coumarin hydroxylase, Coh) is the stabilization of the corresponding mRNA; some
      evidence suggests that proteins binding to CYP2A5 mRNA may be involved in this
      stabilization. Here we report that pyrazole, a well known inducer of CYP2A5 and
      stabilizer of its message, enhances the binding of a set of proteins to 32P
      labelled 3'-untranslated region (3'UTR) of CYP2A5 to give 32P-labelled bands of
      apparent molecular mass 37/39, 45/48 and 70/72 kDa after UV cross-linking/RNase
      cleavage; in addition, we found different proteins binding to other parts of
      CYP2A5 mRNA. The 70/72 kDa bands are also formed with the 3'UTR of c-jun. The
      inducible proteins are found in different cellular subfractions at different
      concentrations, with a maximum of five-fold induction of binding activity in
      microsomes. When a gel-mobility-shift assay was combined with UV cross-linking to
      resolve different pyrazole-inducible RNA-protein complexes into single RNA
      binding protein bands, the smallest complex contained a double band of 37/39 kDa,
      45/48 kDa bands, 70/72 kDa bands, and additional weaker bands at higher molecular
      masses (around 120 kDa). This composition was found also for all other complexes
      detected by gel-mobility-shift assay; occasionally, bands at higher molecular
      masses were also observed. The proteins of the smallest complex might therefore
      represent a core with which other proteins interact to build up larger complexes.
      Binding of proteins 37/39 kDa and 70/72 kDa was located to a 20-base loop and
      adjacent sequences in a 70 nt AU-rich region of the 3'UTR of the CYP2A5. Based on
      our previous evidence, this 70-nt sequence may play an important role in the
      stabilization and processing of the message.

PMID- 9531488
TI  - Triplet structure of human von Willebrand factor.
AB  - Human von Willebrand factor (hp-vWF) is a high-molecular- mass protein found in
      plasma as a series of multimers. It consists of subunits comprising 2050 amino
      acids linked by disulphide bonds into multimers of various size ranging in
      molecular mass up to greater than 10000kDa. Partial proteolysis at position
      Tyr842-Mer843 of the subunit [Dent et al. (1990) Proc. Natl. Acad. Sci. U.S.A.
      87, 6306-6310] by a vWF-specific protease [Furlan et al. (1993) Proc. Natl. Acad.
      Sci. U.S.A. 90, 7503-7507] results in the generation of an N-terminal and a C
      terminal fragment and the appearance of hp-vWF triplet bands. It has been
      suggested [Furlan et al. (1993) Proc. Natl. Acad. Sci. U.S.A. 90, 7503-7507] that
      (i) the intermediate triplet band of the primary dimer represents a dimer of two
      C-terminal fragments, (ii) the slower migrating satellite band of the primary
      dimer represents an asymmetric structure composed of a mature subunit to which
      one N-terminal and one C-terminal fragment are linked by disulphide bonds, and
      (iii) the faster migrating satellite band of the primary dimer contains two N
      terminal fragments. Here we used recombinant vWF (r-vWF) for structural analysis
      of hp-vWF multimers. r-vWF exhibited no proteolytic degradation and all multimers
      contained mature subunits. High-resolution agarose-gel electrophoresis and two
      dimensional electrophoresis demonstrated that (i) r-vWF multimers and hp-vWF
      intermediate triplet bands exhibited identical molecular mass and electrophoretic
      mobilities, (ii) the faster and slower migrating satellite bands of hp-vWF differ
      by less than the molecular mass of one subunit from the corresponding
      intermediate triplet band, and (iii) the triplet bands of hp-vWF are composed of
      mature and degraded subunits. The results support a structural model of hp-vWF
      triplet bands according to which the intermediate triplet bands represent
      multiple numbers of symmetric and/or asymmetric dimers, the slower migrating
      satellite bands have one extra N-terminal fragment, and the faster migrating
      satellite band lacks one N-terminal fragment respectively in comparison with the
      corresponding intermediate triplet band.

PMID- 9531490
TI  - Inactivating peptide of the Shaker B potassium channel: conformational
      preferences inferred from studies on simple model systems.
AB  - Previous studies on the interaction between the inactivating peptide of the
      Shaker B K+ channel (ShB peptide, H2N-MAAVAGLYGLGEDRQHRKKQ) and anionic
      phospholipid vesicles, used as model targets, have shown that the ShB peptide:
      (i) binds to the vesicle surface with high affinity; (ii) readily adopts a
      strongly hydrogen-bonded beta-structure; and (iii) becomes inserted into the
      hydrophobic bilayer. We now report fluorescence studies showing that the vesicle
      inserted ShB peptide is in a monomeric form and, therefore, the observed beta
      structure must be intramolecularly hydrogen-bonded to produce a beta-hairpin
      conformation. Also, additional freeze-fracture and accessibility-to-trypsin
      studies, which aimed to estimate how deeply and in which orientation the folded
      monomeric peptide inserts into the model target, have allowed us to build
      structural models for the target-inserted peptide. In such models, the peptide
      has been folded near G6 to configure a long beta-hairpin modelled to produce an
      internal cancellation of net charges in the stretch comprising amino acids 1-16.
      As to the positively charged C-terminal portion of the ShB peptide (RKKQ), this
      has been modelled to be in parallel with the anionic membrane surface to
      facilitate electrostatic interactions. Since the negatively charged surface and
      the hydrophobic domains in the model vesicle target may partly imitate those
      present at the inactivation 'entrance' in the channel protein [Kukuljan, M.,
      Labarca, P. and Latorre, R. (1995) Am. J. Physiol. Cell Physiol. 268, C535-C556],
      we believe that the structural models postulated here for the vesicle-inserted
      peptide could help to understand how the ShB peptide associates with the channel
      during inactivation and why mutations at specific sites in the ShB peptide
      sequence, such as that in the ShB-L7E peptide, result in non-inactivating peptide
      variants.

PMID- 9531489
TI  - Inhibition of kinases impairs neutrophil activation and killing of Staphylococcus
      aureus.
AB  - Intracellular phosphorylations polymorphonuclear neutrophils are mediated by
      kinases, including mitogen activated-protein (MAP) kinases and
      phosphatidylinositol 3-kinase. In the present study we demonstrate their effector
      functions upon both ligation of cell-surface seven-transmembrane-spanning
      receptors by bacterial peptide formylmethionyl-leucylphenylalanine as well as in
      the process of destruction of Staphylococcus aureus. To regulate neutrophil MAP
      kinases p38 and p44/42, specifically, we made use of their specific inhibitors 10
      microM SK&F 86002 (for p38) and PD 098059 (for activating kinase of p44/42). SK&F
      86002 was a potent inhibitor (by 70%) of induced antimicrobial oxygen-radical
      generation compared with PD 098059 (by 20%). SK&F 86002 and PD 098059 inhibited
      mobilization of a dominant neutrophil adhesion molecule, beta2 integrin, from
      cytoplasmic granules to the plasma membrane by 40 and 10% respectively, and the
      combination of the two drugs resulted in a 90% effect. The combined effect of
      both drugs was moderate inhibition of bacterial destruction, despite the fact
      that neither compound had detectable effect on bactericidal activity if applied
      individually. Bacterial destruction was also inhibited by wortmannin (0.1
      microM), the specific inhibitor of phosphatidylinositol 3-kinase, which had
      previously been described to target various other activations of the neutrophil,
      including oxygen-radical generation. Although the relative contribution of p38
      and p44/42 MAP kinases varied, the marked effects of the combined inhibition of
      the kinases revealed their concerted actions to be critical for normal neutrophil
      function.

PMID- 9531491
TI  - Binding of a burst-phase intermediate formed in the folding of denatured D
      glyceraldehyde-3-phosphate dehydrogenase by chaperonin 60 and 8-anilino-1
      naphthalenesulphonic acid.
AB  - Upon dilution, D-glyceraldehyde-3-phosphate dehydrogenase (GADPH) that has been
      fully inactivated, but only partially unfolded, in dilute guanidine hydrochloride
      (GuHCl) recovers activity completely. The fully unfolded enzyme, however, is re
      activated only to a limited extent after dilution, and refolds rapidly in a burst
      phase to a partially folded intermediate characterized by increases in both the
      emission intensity of intrinsic fluorescence and binding to 8-anilino-1
      naphthalenesulphonic acid (ANS). This intermediate aggregates with a time lag of
      a few minutes, and the aggregation can be suppressed completely by chaperonin 60
      (GroEL). Stoichiometric analysis of the suppression of GAPDH re-activation by
      GroEL suggests that the tetradecameric GroEL binds to a dimeric GAPDH folding
      intermediate. This intermediate can be re-activated by ATP or ATP/chaperonin 10
      (GroES) to an extent considerably greater than that obtained on spontaneous re
      activation of the fully denatured enzyme upon dilution. Probing with a
      fluorescent derivative of NAD+ shows that this folding intermediate does not have
      a native conformation at the active site. The similar profiles of the effects of
      GroEL and ANS on the re-activation of GAPDH denatured by different concentrations
      of GuHCl suggest that GroEL and ANS recognize and bind to the same folding
      intermediate, which is similar to the relatively stable, partially unfolded,
      state of the enzyme denatured in 0.5-1.0 MGuHCl. However, the complexes of the
      intermediate with GroEL or ANS appear to be different, in that GroEL, but not
      ANS, suppresses aggregation and assists folding in the presence of ATP.

PMID- 9531492
TI  - Purification and partial characterization of a peroxidase from plant cell
      cultures of Cassia didymobotrya and biotransformation studies.
AB  - An acidic peroxidase (EC 1.11.1.7) produced by cell suspension cultures of Cassia
      didymobotrya (wild senna) was purified from culture medium collected on the 29th
      day. The enzyme was shown to be a glycoprotein with a pI of 3.5, a molecular mass
      of approx. 43 kDa by SDS/PAGE and 50 kDa by gel filtration. The N-terminal
      sequence was very similar to those of other plant peroxidases. The peroxidase was
      characterized by a high specificity towards coniferyl alcohol and other natural
      phenolics such as guaiacol and ferulic and caffeic acids. These findings suggest
      that the enzyme is involved in lignification processes of the cell wall.
      Moreover, the enzyme was able to catalyse the oxidation of 4,3',4'
      trihydroxychalcone and 4, 3',4'-trihydroxy-3-methoxychalcone to the corresponding
      3, 3'-biflavanones, as mixtures of racemic and meso forms.

PMID- 9531493
TI  - Species-specificity in endoplasmic reticulum signal peptide utilization revealed
      by proteins from Trypanosoma brucei and Leishmania.
AB  - N-Terminal signal peptides direct secretory and most membrane proteins into the
      exocytic pathway at the endoplasmic reticulum. Signal sequences can function
      across kingdoms. However, our attempts at translocating variant surface
      glycoprotein (VSG) 117, VSG MVAT7, VSG 221 and BiP from Trypanosoma brucei and
      gp63 from Leishmania chagasi into canine pancreas microsomes failed. On replacing
      the signal peptide of VSG 117 with that from yeast prepro-alpha-mating factor
      (ppalphaMF) the chimaeric protein was imported, indicating that the signal
      sequence of VSG 117 was incompatible with the protein-import machinery of
      mammalian microsomes. Replacement of the gp63-h-region with a hybrid composed of
      the N-terminal nine residues from the h-region of gp67 from Autographa
      californica nuclear polyhedrosis virus and the C-terminal 10 residues from the h
      region of gp63 from L. major produced a functional signal peptide. Thus, the h
      region of kinetoplastid signal peptides appears to be the subdomain that is non
      functional at the mammalian translocon. The calculated biophysical properties and
      computed discriminant scores (predictive of importability of signal peptides into
      mammalian microsomes) of the kinetoplastid signal sequences nevertheless are
      similar to those of ppalphaMF and Escherichia coli beta-lactamase both of which
      were imported. These signal peptides are the first collection from one biological
      family that have been found to fail to function across a species barrier. They
      indicate that signal peptides are not as universally interchangeable as
      previously believed. Intriguingly, endoplasmic reticulum signal peptides from
      Leishmania and Crithidia fasciculata are reminiscent of signal peptides from Gram
      positive bacteria.

PMID- 9531494
TI  - Activation of S6 kinase in human neutrophils by calcium pyrophosphate dihydrate
      crystals: protein kinase C-dependent and phosphatidylinositol-3-kinase
      independent pathways.
AB  - Phosphatidylinositol 3-kinase (PI 3-kinase) has been shown previously to be a
      central enzyme in crystal-induced neutrophil activation. Since activation of the
      70 kDa S6 kinase (p70S6K) has been shown to be dependent on PI 3-kinase
      activation in mammalian cells, and since the former is a key enzyme in the
      transmission of signals to the cell nucleus, activation of p70(S6K) was
      investigated in crystal-stimulated neutrophils. Cytosolic fractions from calcium
      pyrophosphate dihydrate (CPPD)-crystal-activated neutrophils were separated by
      Mono Q chromatography and analysed for phosphotransferase activity using a range
      of substrates and probed by Western analysis using antibodies to p70(S6K) and
      mitogen-activated protein kinase (MAP kinase). CPPD crystals induced a robust,
      transient activation (peak activity at 2 min) of p70(S6K) that was fully
      inhibited by pretreatment with rapamycin. This is the first report of the
      activation of p70(S6K) in neutrophil signal transduction pathways induced by an
      agonist. This crystal-induced activation of p70(S6K) could also be inhibited by a
      protein kinase C (PKC) inhibitor (Compound 3), but not by the PI 3-kinase
      inhibitor wortmannin. CPPD crystals also activated the ERK1 and ERK2 forms of MAP
      kinase (wortmannin insensitive), PKC (Compound 3 sensitive) and protein kinase B
      (wortmannin sensitive) in neutrophils. These data suggest that activation of
      p70(S6K) may proceed through a PI 3-kinase- and protein kinase B-independent but
      PKC-dependent pathway in crystal-activated neutrophils.

PMID- 9531496
TI  - Study of stereospecificity in mushroom tyrosinase.
AB  - This paper reports experiments on the stereospecificity observed in the
      monophenolase and diphenolase activities of mushroom tyrosinase. Several
      enantiomorphs of monophenols and o-diphenols were assayed: L-tyrosine, D,L
      tyrosine, D-tyrosine; L-alpha-methyltyrosine, D,L-alpha-methyltyrosine; L-dopa,
      D,L-dopa, D-dopa; L-alpha-methyldopa, D,L-alpha-methyldopa; L-isoprenaline, D,L
      isoprenaline and D-isoprenaline. The Vmax values obtained for each series were
      the same. The electronic densities on the carbon atoms in the meta (C-3) and the
      para (C-4) positions of the benzene ring were determined by NMR assays. This
      value is related to the nucleophilic power of the oxygen atom belonging to the
      hydroxy group, which could explain the Vmax values experimentally obtained for
      the monophenolase and diphenolase activities of mushroom tyrosinase. The spatial
      orientation of the ring substituents led to lower Km values for L-isomers than
      for D-isomers. However, the Vmax values were the same for each series of isomers
      because spatial orientation did not affect the NMR value of C-4. Therefore
      mushroom tyrosinase showed stereospecificity in its affinity towards its
      substrates (Km) but not in the transformation reaction rate (Vmax) of these
      substrates.

PMID- 9531495
TI  - Characterization of the leupeptin-inactivating enzyme from Streptomyces
      exfoliatus SMF13 which produces leupeptin.
AB  - Leupeptin-inactivating enzyme (LIE) was purified from Streptomyces exfoliatus
      SMF13 by ammonium sulphate fractionation of cell-free culture broth,
      ultrafiltration, anion-exchange chromatography on DEAE-Sephadex A-50 and gel
      filtration chromatography on Sephadex G-75. The molecular mass of the purified
      enzyme was measured as 34700 Da and the N-terminal amino acid sequence was
      APTPPDIPLANVPA. Acetyl-leucine, leucine and argininal were identified as the
      products of leupeptin inactivated by the LIE, indicating that leupeptin is
      inactivated by hydrolysis of peptide bond between leucine and leucine and between
      leucine and argininal of leupeptin (acetyl-leucine-leucine-argininal). Synthetic
      peptide substrates specificity of LIE showed that LIE has absolute specificity
      for peptide bonds with leucine in the P1 position, suggesting that LIE is a
      leucine-specific protease. The optimum pH and temperature were pH 9.0 and 45
      degrees C, respectively. LIE activity was inhibited by metalloprotease inhibitors
      such as EDTA, EGTA, o-phenanthroline and bestatin, but activated by Mg2+ and
      Ca2+, suggesting that the enzyme is a metalloprotease. Aerial-mycelium growth and
      aerial spore formation of S. exfoliatus SMF13 were inhibited by the addition of
      bestatin, an inhibitor of LIE. The inhibition of morphological differentiation
      was due to the inhibition of trypsin-like protease (TLP) activity, which is
      essential for aerial-mycelium formation and is inhibited specifically by
      remaining leupeptin that was not inactivated. These results show that LIEs play a
      role in controlling the amount of leupeptin during colony development. Therefore,
      it is suggested that the physiological function of LIE is to inactivate leupeptin
      when or where TLP activity is required for aerial-mycelium formation.

PMID- 9531497
TI  - A distinct difference in the metabolic stimulus-response coupling pathways for
      regulating proinsulin biosynthesis and insulin secretion that lies at the level
      of a requirement for fatty acyl moieties.
AB  - The regulation of proinsulin biosynthesis in pancreatic beta-cells is vital for
      maintaining optimal insulin stores for glucose-induced insulin release. The
      majority of nutrient fuels that induce insulin release also stimulate proinsulin
      biosynthesis, but since insulin exocytosis and proinsulin synthesis involve
      different cellular mechanisms, a point of divergence in the respective metabolic
      stimulus-response coupling pathways must exist. A parallel examination of the
      metabolic regulation of proinsulin biosynthesis and insulin secretion was
      undertaken in the same beta-cells. In MIN6 cells, glucose-induced proinsulin
      biosynthesis and insulin release shared a requirement for glycolysis to generate
      stimulus-coupling signals. Pyruvate stimulated both proinsulin synthesis
      (threshold 0.13-0.2 mM) and insulin release (threshold 0.2-0.3 mM) in MIN6 cells,
      which was eliminated by an inhibitor of pyruvate transport (1 mM alpha-cyano-4
      hydroxycinnamate). A combination of alpha-oxoisohexanoate and glutamine also
      stimulated proinsulin biosynthesis and insulin release in MIN6 cells, which,
      together with the effect of pyruvate, indicated that anaplerosis was necessary
      for instigating secondary metabolic stimulus-coupling signals in the beta-cell. A
      consequence of increased anaplerosis in beta-cells is a marked increase in
      malonyl-CoA, which in turn inhibits beta-oxidation and elevates cytosolic fatty
      acyl-CoA levels. In the beta-cell, long-chain fatty acyl moieties have been
      strongly implicated as metabolic stimulus-coupling signals for regulating insulin
      exocytosis. Indeed, it was found in MIN6 cells and isolated rat pancreatic islets
      that exogenous oleate, palmitate and 2-bromopalmitate all markedly potentiated
      glucose-induced insulin release. However, in the very same beta-cells, these
      fatty acids in contrast inhibited glucose-induced proinsulin biosynthesis. This
      implies that neither fatty acyl moieties nor beta-oxidation are required for the
      metabolic stimulus-response coupling pathway specific for proinsulin
      biosynthesis, and represent an early point of divergence of the two signalling
      pathways for metabolic regulation of proinsulin biosynthesis and insulin release.
      Therefore alternative metabolic stimulus-coupling factors for the specific
      control of proinsulin biosynthesis at the translational level were considered.
      One possibility examined was an increase in glycerophosphate shuttle activity and
      change in cytosolic redox state of the beta-cell, as reflected by changes in the
      ratio of alpha-glycerophosphate to dihydroxyacetone phosphate. Although 16.7 mM
      glucose produced a significant rise in the alpha
      glycerophosphate/dihydroxyacetone phosphate ratio, 1 mM pyruvate did not. It
      follows that the cytosolic redox state and fatty acyl moieties are not
      necessarily involved as secondary metabolic stimulus-coupling factors for
      regulation of proinsulin biosynthesis. However, the results indicate that
      glycolysis and the subsequent increase in anaplerosis are indeed necessary for
      this signalling pathway, and therefore an extramitochondrial product of beta-cell
      pyruvate metabolism (that is upstream of the increased cytosolic fatty acyl-CoA)
      acts as a key intracellular secondary signal for specific control of proinsulin
      biosynthesis by glucose at the level of translation.

PMID- 9531498
TI  - Metabolism and apoptotic properties of elevated ceramide in HT29rev cells.
AB  - Ceramide (Cer) has been implicated in the regulation of apoptosis. In this study,
      we elevated cellular Cer levels in human colon-carcinoma (HT29(rev)) cells by
      incubating the cells in the presence of bacterial sphingomyelinase (bSMase) or,
      alternatively, in the presence of C2-Cer, a short-chain analogue of the
      sphingolipid. bSMase treatment did not induce apoptosis in these cells, as
      revealed by a lack of both DNA fragmentation and cleavage of poly(ADP
      ribose)polymerase. In contrast, apoptosis did occur upon addition of C2-Cer.
      These findings led us to study whether differences in the metabolic fate of the
      excess of Cer, as generated by both treatments, contributed to the observed
      difference in apoptosis-inducing capacity. C2-Cer was rapidly taken up by
      HT29(rev) cells and accumulated due to the absence of substantial metabolic
      conversion. Upon addition of bSMase, hydrolysis of sphingomyelin resulted in a
      reduction of that pool to 20% compared with control values, accompanied by a
      multi-fold increase in Cer level. In spite of the continuous presence of active
      bSMase, the Cer increase turned out to be transient. Cer levels reached their
      maximum 1-2 h after addition of bSMase, followed by a significant decrease.
      Excessive Cer was mainly turned over via cerebrosides into complex glycolipids,
      including gangliosides. In the presence of glucosylceramide synthase- and/or
      ceramidase inhibitors, this conversion was significantly blocked and bSMase
      generated Cer accumulated in the cells. However, even under these conditions
      apoptosis did not occur. In conclusion, the inability of bSMase to induce
      apoptosis of HT29(rev) cells does not appear to be due to rapid metabolic
      conversion of excessive Cer. Since apoptosis is induced upon addition of C2-Cer,
      we therefore propose that the intracellular target involved in the propagation of
      the apoptotic signal is reached by C2-Cer, but not by bSMase-generated Cer.

PMID- 9531499
TI  - Fixed-point methods for computing the equilibrium composition of complex
      biochemical mixtures.
AB  - The fixed-point algebraic method [Storer and Cornish-Bowden (1976) Biochem. J.
      159, 1-5] for computing the concentrations at equilibrium of complex biochemical
      mixtures fails for many binding stoichiometries, especially those that include
      molecular self-association. A typical example is the monomer-dimer-tetramer
      equilibrium. This paper reports two main results. First, the above algorithm is
      analysed theoretically to predict for which binding stoichiometries it succeeds
      and for which it will fail. Secondly, an alternative algorithm is described for
      self-associating biochemical systems. Illustrative examples are based on the
      dimeric proteinase from HIV.

PMID- 9531500
TI  - alpha- and delta-tocopherol induce expression of hepatic alpha-tocopherol
      transfer-protein mRNA.
AB  - alpha-Tocopherol transfer protein (alpha-TTP) supplements nascent very-low
      density lipoprotein (VLDL) preferentially with alpha-tocopherol by selecting the
      alpha-isomers against other stereoisomers of tocopherol. It is exclusively
      expressed in liver. We investigated whether the expression of the hepatic alpha
      TTP can be induced by dietary tocopherols. Vitamin E-depleted rats were fed with
      a diet containing alpha- and delta-tocopherol (ratio 1:3). The expression of
      alpha-TTP mRNA was measured in liver tissue. The ratio of tocopherol
      stereoisomers was determined in plasma, plasma lipoproteins and tissues to
      measure the metabolic action of alpha-TTP. Refeeding a diet containing either
      alpha- or delta-tocopherol, or both, caused a steady increase of the expression
      of alpha-TTP mRNA. In parallel the alpha/delta-tocopherol ratio increased in
      plasma, VLDL, high-density lipoprotein and low-density lipoprotein as well as in
      liver tissue, when the diet was fed containing both isomers. The alpha
      tocopherol/delta-tocopherol ratio of heart, kidney, lung, lamellar bodies of lung
      and in lung lavage showed no or a comparatively low increase. The data show that
      both tocopherol isomers were able to induce alpha-TTP mRNA in rat liver and,
      thus, the ability of liver to select for the alpha-isomer. On the other hand,
      tocopherol depletion did not change the expression of hepatic alpha-TTP mRNA in
      the rat.

PMID- 9531501
TI  - Two types of H+-ATPase are involved in the acidification of internal compartments
      in Trypanosoma cruzi.
AB  - ATP-driven acidification of internal compartments of Trypanosoma cruzi
      epimastigotes was assayed spectrophotometrically with Acridine Orange and cells
      permeabilized with filipin. H+-ATPase activity was not inhibited fully by either
      500 nM concanamycin A or 500 microM orthovanadate, but a combination of 5 nM
      concanamycin A and 25 microM vanadate completely inhibited activity, suggesting
      the operation of separate V-type (concanamycin-sensitive) and P-type (vanadate
      sensitive) H+-ATPase activities in the permeabilized cells. This was supported by
      different kinetics of Acridine Orange uptake seen in the presence of the
      different inhibitors, and by different optimal protein (cell) concentrations for
      the two apparent activities. The use of different buffers further distinguished
      the ATPases. The V-H+-ATPase activity was stimulated by K+ and inhibited by a
      lack of anions or the replacement of Cl- with gluconate. The P-type H+-ATPase
      activity was not affected by a lack of Cl- or K+ but was substantially inhibited
      in a largely anion-free buffer. This inhibition could be annulled by the addition
      of the K+ ionophore valinomycin, which probably acted via the establishment of a
      countercurrent efflux of K+ from the compartment containing the P-type H+-ATPase
      and the relief of the potential difference generated by the electrogenic proton
      pump. Valinomycin showed some stimulation of P-type activity in all buffers
      tested, but its effects on V-H+-ATPase activity were at best transient except in
      a K+-free buffer, which suggested that the V-H+-ATPase was located in an
      organelle with relatively low [K+] that was different from that which
      accommodated the P-type activity. On the basis of acidity and K+ content, these
      organelles might correspond, in part at least, to the acidocalcisomes (V-H+
      ATPase activity) and the reservosomes (P-type activity) previously identified in
      these cells. Both activities could also be found in the human-infective forms of
      the parasite, amastigotes and trypomastigotes, but the P-type activity was
      relatively weak in these cells types, which is correlated with a lack of
      reservosomes in these forms.

PMID- 9531503
TI  - Peroxynitrite modulates tyrosine phosphorylation and phosphoinositide signalling
      in human neuroblastoma SH-SY5Y cells: attenuated effects in human 1321N1
      astrocytoma cells.
AB  - Peroxynitrite may contribute to oxidative stress involving neurodegeneration in
      several disorders, including Alzheimer's disease. As with other reactive oxygen
      species, peroxynitrite might affect neuronal signalling systems, actions that
      could contribute to adaptive or deleterious cellular outcomes, but such effects
      have not previously been studied. To address this issue directly, peroxynitrite
      (50-500 microM) was administered to human neuroblastoma SH-SY5Y cells to assess
      its effects on protein tyrosine nitration, phosphoinositide signalling and
      protein tyrosine phosphorylation. Peroxynitrite rapidly increased the
      nitrotyrosine immunoreactivity of numerous proteins, primarily in the cytosol.
      Peroxynitrite inhibited, in a concentration-dependent manner, phosphoinositide
      hydrolysis stimulated by activation of muscarinic receptors with carbachol and
      the inhibition was greater after the depletion of cellular glutathione. In
      comparison, muscarinic receptor-stimulated phosphoinositide hydrolysis in human
      astrocytoma 1321N1 cells was less vulnerable to inhibition by peroxynitrite
      either without or with prior depletion of glutathione. There was a large, rapid
      and reversible increase in the tyrosine phosphorylation of the p120 Src substrate
      in peroxynitrite-treated SH-SY5Y cells, a response that was potentiated by
      glutathione depletion; in contrast, peroxynitrite decreased the tyrosine
      phosphorylation of focal adhesion kinase and paxillin. Tyrosine phosphorylation
      of p120 in 1321N1 astrocytoma cells was less sensitive to modulation by
      peroxynitrite. Thus alterations in phosphoinositide signalling and protein
      tyrosine phosphorylation were greater in neuroblastoma than astrocytoma cells,
      and modulation of these signalling processes probably contributes to neuronal
      mechanisms of the response to peroxynitrite.

PMID- 9531502
TI  - Involvement of the Ras/extracellular signal-regulated kinase signalling pathway
      in the regulation of ERCC-1 mRNA levels by insulin.
AB  - Expression of DNA repair enzymes, which includes ERCC-1, might be under the
      control of hormonal and growth factor stimulation. In the present study it was
      observed that insulin increased ERCC-1 mRNA levels both in Chinese hamster ovary
      cells overexpressing human insulin receptors (HIRc cells) and in fully
      differentiated 3T3-L1 adipocytes. To investigate the mechanisms underlying the
      increase in ERCC-1 gene expression in HIRc cells, we used a variety of
      pharmacological tools known to inhibit distinct signalling pathways. None of
      these inhibitors affected the amount of ERCC-1 mRNA in unstimulated cells. The
      pretreatment of cells with two chemically unrelated phosphatidylinositol 3'
      kinase inhibitors, wortmannin and LY294002, failed to block the doubling of ERCC
      1 mRNA content by insulin. Similarly, inhibition of pp70 S6 kinase by rapamycin
      had no apparent effects on this insulin response. In contrast, altering the
      p21(ras)-dependent pathway with either manumycin, an inhibitor of Ras
      farnesylation, or PD98059, an inhibitor of the mitogen-activated protein
      kinase/extracellular signal-regulated protein kinase (ERK) kinase, suppressed the
      induction of ERCC-1 mRNA by insulin (P<0.001). Furthermore inhibition of RNA and
      protein synthesis negatively regulated the expression of this insulin-regulated
      gene (P<0.005). These results suggest that insulin enhances ERCC-1 mRNA levels by
      the activation of the Ras-ERK-dependent pathway without the involvement of the
      phosphatidylinositol 3'-kinase/pp70 S6 kinase.

PMID- 9531505
TI  - Mevalonate-derived isopentenyl diphosphate is the biosynthetic precursor of
      ubiquinone prenyl side chain in tobacco BY-2 cells.
AB  - Study of the incorporation of 13C-labelled glucose or pyruvate into the
      isoprenoids of tobacco BY-2 cells allowed the biosynthetic origin of isopentenyl
      diphosphate to be determined. Sterols synthesized in the cytoplasm and the prenyl
      chain of ubiquinone Q10 located in mitochondria were derived from the same
      isopentenyl diphosphate pool, synthesized from acetyl-CoA through mevalonate,
      whereas the prenyl chain of plastoquinone was obtained from the mevalonate
      independent glyceraldehyde 3-phosphate/pyruvate route, like all chloroplast
      isoprenoids from higher plants. These results are in accord with the
      compartmentation and complete enzymic independence of the biosynthesis of long
      chain all-trans polyprenols in mitochondria and chloroplasts.

PMID- 9531504
TI  - Structure of the human hexokinase type I gene and nucleotide sequence of the 5'
      flanking region.
AB  - This study reports the precise intron/exon boundaries and intron/exon composition
      of the human hexokinase type I gene. A yeast artificial chromosome containing the
      hexokinase type I gene was isolated from the yeast artificial chromosome library
      of the Centre d'Etude du Polymorphisme Humaine. A cosmid sublibrary was created
      and direct sequencing of the individual cosmids was used to provide the
      exon/intron organization. The human hexokinase type I gene was found to be
      composed of 18 exons ranging in size from 63 to 305 bp. Intron 1 is at least 15
      kb in length, whereas intron 2 spans at least 10 kb. Overall, the length of the
      17 introns ranges from 104 to greater than 15 kb. The entire coding region is
      contained in at least 75 kb of the gene. The structure of the gene reveals a
      remarkable conservation of the size of the exons compared with glucokinase and
      hexokinase type II. Isolation of the 5' flanking region of the gene revealed a 75
      90% identity with the rat sequence. Direct evidence of an alternative red-blood
      cell-specific exon 1 located upstream of the 5' flanking region of the gene is
      also provided.

PMID- 9531506
TI  - Histones and basic polypeptides activate Ca2+/cation influx in various cell
      types.
AB  - Histone H2A (1-10 microg/ml) added to Ehrlich ascite cell suspensions promoted:
      (i) Ca2+ influx, but no apparent intracellular Ca2+ mobilization; (ii) plasma
      membrane depolarization and Na+ influx in Ca2+-free medium, which were recovered
      by Ca2+ readmission; (iii) influx of other cations such as Ba2+, Mn2+, choline+
      and N-methyl-d-glucamine+, but not of propidium+, ethidium bromide and Trypan
      Blue. H2A-induced Ca2+ influx and cell depolarization were: (i) blocked by La3+
      and Gd3+, but not by various inhibitors of receptor-activated Ca2+-influx
      pathways/channels; (ii) mimicked by various basic polypeptides, with Mr>4000;
      (iii) prevented or reversed by polyanions such as polyglutamate or heparin; (iv)
      present in other cell types, such as Jurkat, PC12 and Friend erythroleukaemia
      cells, but virtually absent from rat hepatocytes and thymocytes. We conclude that
      cationic proteins/polypeptides, by interacting in a cell-specific manner with the
      cell surface, can activate in those cells putative non-selective Ca2+ channels
      and membrane depolarization.

PMID- 9531507
TI  - cDNA cloning reveals two mouse beta5 integrin transcripts distinct in cytoplasmic
      domains as a result of alternative splicing.
AB  - The integrin beta5 subunit has only been found to form a heterodimer with subunit
      alphav which acts as a vitronectin receptor. Integrin alphavbeta5 has been
      implicated in cell migration and growth factor-induced angiogenesis. In the
      present study, a mouse liver cDNA library was screened using a human beta5 cDNA
      fragment obtained by reverse transcriptase PCR (RT-PCR). Three of the clones
      (MB5, MB15 and MB17) overlapped to give an open reading frame, called beta5A,
      which is homologous to the human beta5 subunit. The sequence of another clone
      (MB26), called beta5B, was identical with beta5A, except for a deletion of 29 bp
      near the 3' end of the open reading frame. The 29 bp deletion resulted in an open
      reading-frame shift and a completely different C-terminal sequence in beta5B.
      beta5A and beta5B were shown, by RT-PCR, to be co-expressed in most mouse tissues
      tested, although beta5B mRNA was detected at much lower levels than beta5A.
      beta5A and beta5B mRNAs were also detected in the mouse monocytic cell line,
      J774, and in isolated mouse peritoneal macrophages. Adhesion of peritoneal
      macrophages has been shown to up-regulate the expression of both beta5A and
      beta5B mRNAs. The 29 bp sequence begins with a putative intron-splicing donor
      site (GTGAT...). A 3' fragment of the mouse integrin beta5 gene was cloned by PCR
      and sequenced showing that the 29 bp sequence was also immediately followed by an
      intron. Therefore, the 29 bp sequence was apparently expressed as part of the
      beta5A mRNA but was spliced out as part of the downstream intron in beta5B. Since
      the cytoplasmic domains of the integrin beta subunits are important in
      cytoskeleton attachment and signalling, the two alternatively spliced beta5
      isoforms may have distinct roles in cell adhesion and other cellular functions.

PMID- 9531508
TI  - Cystathionine gamma-synthase from Arabidopsis thaliana: purification and
      biochemical characterization of the recombinant enzyme overexpressed in
      Escherichia coli.
AB  - Cystathionine gamma-synthase catalyses the first reaction specific for methionine
      biosynthesis in plants, the gamma-replacement of the phosphoryl substituent of O
      phosphohomoserine by cysteine. A cDNA encoding cystathionine gamma-synthase from
      Arabidopsis thaliana has been cloned and used to overexpress the enzyme in
      Escherichia coli. The native recombinant enzyme is a homotetramer composed of 53
      kDa subunits, each being tightly associated with one molecule of pyridoxal 5'
      phosphate that binds at lysine-379 of the protein precursor. The replacement
      reaction follows a Ping Pong mechanism with a Vmax of 33.6 units/mg and Km values
      of 2.5 mM and 460 microM for O-phosphohomoserine and cysteine respectively. The
      protective effect of O-phosphohomoserine against enzyme inactivation by
      propargylglycine indicated that the Kd for the substrate is approx. 1/2500 of its
      Km value. Thus most of these biochemical properties are similar to those
      previously reported for plant and bacterial cystathionine gamma-synthases.
      However, the plant enzyme differs markedly from its enterobacterial counterparts
      because it catalyses a very faint gamma-elimination of O-phosphohomoserine in the
      absence of cysteine, this process being about 1/2700 as fast as the gamma
      replacement reaction and approx. 1/1500 as fast as the gamma-elimination
      catalysed by the E. coli enzyme. This huge difference could be attributed to the
      inability of the A. thaliana cystathionine gamma-synthase to accumulate a long
      wavelength-absorbing species that is characteristic for the efficient gamma
      elimination reaction catalysed by the enterobacterial enzyme.

PMID- 9531509
TI  - Purification of catalytic domain of rat spleen p72syk kinase and its
      phosphorylation and activation by protein kinase C.
AB  - The catalytic domain of p72(syk) kinase (CDp72(syk)) was purified from a 30000 g
      particulate fraction of rat spleen. The purification procedure employed
      sequential chromatography on columns of DEAE-Sephacel and Superdex-200, and
      elution from HA-Ultrogel by chloride. The analysis of the final CDp72(syk)
      preparation by SDS/PAGE revealed a major silver-stained 40 kDa protein. The
      kinase was identified by covalent modification of its ATP-binding site with
      [14C]5'-fluorosulphonylbenzoyladenosine and by immunoblotting with a polyclonal
      antibody against the 'linker' region of p72(syk). By using poly(Glu4, Tyr1) as a
      substrate, the specific activity of the enzyme was determined as 18.5 nmol Pi/min
      per mg. Casein, histones H1 and H2B and myelin basic protein were efficiently
      phosphorylated by CDp72(syk). The kinase exhibited a limited ability to
      phosphorylate random polymers containing tyrosine residues. CDp72(syk)
      autophosphorylation activity was associated with an activation of the kinase
      towards exogenous substrates. The extent of activation was dependent on the
      substrates added. CDp72(syk) was phosphorylated by protein kinase C (PKC) on
      serine and threonine residues. With a newly developed assay method, we
      demonstrated that the PKC-mediated phosphorylation had a strong activating effect
      on the tyrosine kinase activity of CDp72(syk). Studies extended to conventional
      PKC isoforms revealed an isoform-dependent manner (alpha > betaI = betaII >
      gamma) of CDp72(syk) phosphorylation. The different phosphorylation efficiencies
      of the PKC isoforms closely correlated with the ability to enhance the tyrosine
      kinase activity.

PMID- 9531510
TI  - S-Nitrosoglutathione is a substrate for rat alcohol dehydrogenase class III
      isoenzyme.
AB  - An enzyme isolated from rat liver cytosol (native molecular mass 78. 3 kDa;
      polypeptide molecular mass 42.5 kDa) is capable of catalysing the NADH/NADPH
      dependent degradation of S-nitrosoglutathione (GSNO). The activity utilizes 1 mol
      of coenzyme per mol of GSNO processed. The isolated enzyme has, as well, several
      characteristics that are unique to alcohol dehydrogenase (ADH) class III
      isoenzyme: it is capable of catalysing the NAD+-dependent oxidations of octanol
      (insensitive to inhibition by 4-methylpyrazole), methylcrotyl alcohol (stimulated
      by added pentanoate) and 12-hydroxydodecanoic acid, and also the NADH/NADPH
      dependent reduction of octanal. Methanol and ethanol oxidation activity is
      minimal. The enzyme has formaldehyde dehydrogenase activity in that it is capable
      of catalysing the NAD+/NADP+-dependent oxidation of S-hydroxymethylglutathione.
      Treatment with the arginine-specific reagent phenylglyoxal prevents the
      pentanoate stimulation of methylcrotyl alcohol oxidation and markedly diminishes
      the enzymic activity towards octanol, 12-hydroxydodecanoic acid and S
      hydroxymethylglutathione; the capacity to catalyse GSNO degradation is also
      checked. Additionally, limited peptide sequencing indicates 100% correspondence
      with known ADH class III isoenzyme sequences. Kinetic studies demonstrate that
      GSNO is an exceptionally active substrate for this enzyme. S-Nitroso-N
      acetylpenicillamine and S-nitrosated human serum albumin are not substrates; the
      activity towards S-nitrosated glutathione mono- and di-ethyl esters is minimal.
      Product analysis suggests that glutathione sulphinamide is the major stable
      product of enzymic GSNO processing, with minor yields of GSSG and NH3; GSH,
      hydroxylamine, nitrite, nitrate and nitric oxide accumulations are minimal.
      Inclusion of GSH in the reaction mix decreases the yield of the supposed
      glutathione sulphinamide in favor of GSSG and hydroxylamine.

PMID- 9531511
TI  - Insulin targeting to the regulated secretory pathway after fusion with green
      fluorescent protein and firefly luciferase.
AB  - We have prepared recombinant cDNAs encoding chimaeras between human preproinsulin
      (sp.B.C.A., for B-, Connecting- and A-peptides) and a thermostable mutant of
      green fluorescent protein (GFPS65T,V163A, GFP*). The subcellular localization of
      the expressed chimaeras was monitored in living insulin-secreting INS-1 beta
      cells by laser scanning confocal microscopy. When GFP* was fused at the immediate
      N-terminus of the B-chain (sp.[GFP*].B.C.A.myc) two distinct patterns of
      fluorescence were apparent. In 1530/1740 cells examined, fluorescence was
      confined to a reticular, exclusively extranuclear structure, and closely co
      localized with the endoplasmic reticulum marker, calreticulin. However, 210/1740
      (12.1%) of cells displayed punctate fluorescence, which partially co-localized
      with the trans-Golgi network marker, TGN 38, and with the dense core secretory
      granule marker, phogrin. Since secretion of GFP* fluorescence into the medium
      could not readily be measured, we prepared a chimaera in which firefly luciferase
      was fused at the C-terminus of proinsulin (sp.B.C.A.myc.[Luc]). This chimaera
      displayed a distribution closely similar to that of sp.[GFP*].B.C.A. myc, but
      with a lower proportion (15/310, 4.8%) of the cells showing clear punctate
      distribution. At substimulatory glucose concentrations (3 mM) secretion of
      sp.B.C.A.myc.[Luc] could not be detected (rate of release into the medium
      identical with that of the cytosolic Renilla reniformis luciferase), indicating
      that the chimaera did not enter the constitutive secretory pathway. However,
      elevated (30 mM) glucose stimulated the release of the sp.B.C.A.myc. [Luc]
      luciferase chimaera, without a detectable effect on R. reniformis luciferase
      release. These data suggest that fusion of insulin, and the much larger
      photoproteins GFP* and luciferase, leads predominantly to misfolding and
      retention in the endoplasmic reticulum. However, the properly folded chimaeras
      are apparently still correctly targeted to the regulated, rather than the
      constitutive, secretory pathway. These chimaeras should therefore be valuable
      tools to monitor the exocytosis of insulin in real time.

PMID- 9531512
TI  - Specificity of cysteine-rich domains in diacylglycerol kinases and protein
      kinases C.

PMID- 9531513
TI  - Tolterodine, a new muscarinic receptor antagonist, is metabolized by cytochromes
      P450 2D6 and 3A in human liver microsomes.
AB  - Tolterodine, a new muscarinic receptor antagonist, is metabolized via two
      pathways: oxidation of the 5-methyl group and dealkylation of the nitrogen. In an
      attempt to identify the specific cytochrome P450 enzymes involved in the
      metabolic pathway, tolterodine was incubated with microsomes from 10 different
      human liver samples where various cytochrome P450 activities had been rank
      ordered. Strong correlation was found between the formation of the 5
      hydroxymethyl metabolite of tolterodine (5-HM) and CYP2D6 activity (r2, 0.87), as
      well as between the formation of N-dealkylated tolterodine and CYP3A activity
      (r2, 0.97). When tolterodine was incubated with human liver microsomes in the
      presence of compounds known to interact with different P450 isoforms, quinidine
      was found to be the strongest inhibitor of the formation of 5-HM. Ketoconazole
      and troleandomycin were found to be the strongest inhibitors of the formation of
      N-dealkylated tolterodine. A weak inhibitory effect on the formation of N
      dealkylated tolterodine was found with sulfaphenazole, whereas tranylcypromine
      did not inhibit the formation of this metabolite. Microsomes from cells
      overexpressing CYP2D6 formed 5-HM, whereas N-dealkylated tolterodine was formed
      by microsomes expressing CYP2C9, -2C19, and -3A4. The Km for formation of N
      dealkylated tolterodine by CYP3A4 was similar to that obtained in human liver
      microsomes and higher for CYP2C9 and -2C19. We conclude from these studies that
      the formation of 5-HM is catalyzed by CYP2D6 and that the formation of N
      dealkylated tolterodine is predominantly catalyzed by CYP3A isoenzymes in human
      liver microsomes.

PMID- 9531514
TI  - Isolation, purification, and structural characterization of flunixin glucuronide
      in the urine of greyhound dogs.
AB  - A urinary metabolite of flunixin in greyhound dogs was isolated and purified by a
      gradient-elution solid-phase extraction technique. The purified metabolite was
      shown to be hydrolyzed to free flunixin by strong base and by beta-glucuronidase,
      suggesting the presence of a C1-beta-glucuronide ester of flunixin. The
      metabolite was further characterized by positive-ion, tandem MS with electrospray
      ionization. Mass spectral data showed the presence of a protonated molecular ion
      (M+1) at m/z 473, which was consistent with the molecular weight of protonated
      flunixin glucuronide, and a product ion at m/z 297, which was consistent with the
      molecular weight of protonated flunixin. Collisionally induced dissociation of
      the m/z 297 product ion showed a fragmentation pattern consistent with that of
      standard flunixin. These data support the contention that this metabolite of
      flunixin in greyhound urine is the C1-beta-glucuronide of flunixin. Acyl
      glucuronide metabolites of some organic acid drugs have been shown to bind
      covalently to tissue proteins in vitro, in vivo, and ex vivo. The presence of
      this metabolite may, therefore, have pharmacokinetic and pharmacodynamic
      implications for flunixin in greyhound dogs, as well as in other animal species
      in which the acyl glucuronide of flunixin is a metabolite.

PMID- 9531515
TI  - Development of a non-high pressure liquid chromatography assay to determine
      testosterone hydroxylase (CYP3A) activity in human liver microsomes.
AB  - The major pathway of testosterone oxidation by human liver microsomes is the
      formation of 6beta-hydroxytestosterone, which is catalyzed by CYP3A4/5 and which
      accounts for 75-80% of all metabolites formed. In the present study, we describe
      a non-high pressure liquid chromatography assay (HPLC) of CYP3A4/5 activity based
      on the release of tritium (with formation of tritiated water) upon incubation of
      [1,2,6,7-3H]testosterone with human liver microsomes and NADPH. Unreacted
      testosterone and its metabolites were quantitatively extracted from the
      incubation mixture with activated charcoal under conditions that resulted in no
      extraction of tritiated water. The amount of tritiated water formed was
      quantified by liquid scintillation spectrometry and compared with the amount of
      hydroxylated testosterone metabolites formed, as determined by HPLC. Rates of
      tritium release from [1,2,6, 7-3H]testosterone paralleled rates of testosterone
      6beta-hydroxylation as a function of incubation time, the amount of microsomal
      protein, and the concentration of substrate (which yielded identical apparent Km
      and Vmax values). The sample-to-sample variation in tritium release from [1,2,6,7
      3H]testosterone with a panel of human liver microsomes was highly correlated with
      rates of testosterone 6beta-hydroxylation and terfenadine metabolism, two
      commonly used markers of CYP3A activity. Several recombinant human P450 enzymes
      were incubated with [1,2,6,7-3H]testosterone, and only cDNA-expressed CYP3A4
      catalyzed a high rate of tritium release. The close agreement between the tritium
      release assay and HPLC procedure for measuring testosterone oxidation indicates
      that tritium release from [1,2,6,7-3H]testosterone provides a simple and rapid
      alternative to the HPLC procedure for measuring CYP3A4/5 activity in human liver
      microsomes. However, the tritium-release assay may have limited value in
      measuring CYP3A activity in liver microsomes from other species due to the
      presence of other P450 enzymes that can catalyze tritium release from [1,2,6,7
      3H]testosterone.

PMID- 9531516
TI  - Development of a non-high pressure liquid chromatography assay to determine
      [14C]chlorzoxazone 6-hydroxylase (CYP2E1) activity in human liver microsomes.
AB  - The activity of liver microsomal CYP2E1 is commonly measured as the rate of 5
      chloro-2-benzoxazolone (chlorzoxazone) 6-hydroxylation, which requires separation
      of 6-hydroxychlorzoxazone and chlorzoxazone by high pressure liquid
      chromatography (HPLC). In the present study, we describe a solvent extraction
      (non-HPLC) assay for measuring CYP2E1 activity, based on the 6-hydroxylation of
      [14C]chlorzoxazone. When [14C]chlorzoxazone was incubated with human or rat liver
      microsomes in the presence of NADPH, the major product formed was 6
      [14C]hydroxychlorzoxazone. Unreacted [14C]chlorzoxazone was quantitatively
      extracted from the incubation mixture with dichloromethane under conditions that
      resulted in approximately 45% extraction of 6-[14C]hydroxychlorzoxazone. The
      amount of 6-[14C]hydroxychlorzoxazone remaining in the aqueous incubation mixture
      ( approximately 55% of the total amount formed) was quantified by liquid
      scintillation spectrometry. The limit of detection for this assay was 100 pmol of
      6-[14C]hydroxychlorzoxazone. The solvent extraction procedure was validated by
      comparing the rates of formation of 6-[14C]hydroxychlorzoxazone with those
      determined by HPLC under a variety of experimental conditions. The close
      correspondence between the two analytical methods suggests that the extraction
      procedure for measuring 6-[14C]hydroxychlorzoxazone provides a simple, sensitive,
      and rapid alternative to the HPLC procedure for measuring CYP2E1 activity. In
      rats, the assay is not specific for CYP2E1 because CYP1A1 also catalyzes the 6
      hydroxylation of chlorzoxazone. Recombinant human CYP1A1 also catalyzed the 6
      hydroxylation of chlorzoxazone (at (1)/(5) the rate of CYP2E1), although CYP1A1
      is not expressed in human liver microsomes. The non-HPLC assay was used to
      investigate the postulated role of CYP1A2 in the 6-hydroxylation of chlorzoxazone
      by human liver microsomes. Recombinant CYP1A2 did not catalyze the 6
      hydroxylation of chlorzoxazone, and studies with 1-[(3,4-dimethoxyphenyl)methyl]
      6,7-dimethoxyisoquinoline, which inhibits CYP1A2 but not CYP2E1, indicated that,
      in human liver microsomes, the 6-hydroxylation of chlorzoxazone is catalyzed by
      CYP2E1 with little or no contribution from CYP1A2 enzymes over a wide range of
      substrate concentrations.

PMID- 9531517
TI  - Metabolism of beta-arteether to dihydroqinghaosu by human liver microsomes and
      recombinant cytochrome P450.
AB  - beta-Arteether (AE) is an endoperoxide sesquiterpene lactone derivative currently
      being developed for the treatment of severe, complicated malaria caused by
      multidrug-resistant Plasmodium falciparum. Studies were undertaken to determine
      which form(s) of human cytochrome P-450 catalyze the conversion of beta-arteether
      to its deethylated metabolite, dihydroqinghaosu (DQHS), itself a potent
      antimalarial compound. In human liver microsomes, AE was metabolized to DQHS with
      a Km of 53.7 +/- 29.5 microM and a Vmax of 1.64 +/- 1. 78 nmol DQHS/min/mg
      protein. AE biotransformation to DQHS was inhibited by ketoconazole and
      troleandomycin. Ketoconazole was a competitive inhibitor, with an apparent Ki of
      0.33 +/- 0.11 microM. Because AE is being developed for patients who fail primary
      treatment, it is possible that AE may be involved in life-threatening drug-drug
      interactions, such as the associated cardiotoxicity of mefloquine and quinidine.
      Coincubation of AE with other antimalarials showed mefloquine and quinidine to be
      competitive inhibitors with a mean Ki of 41 and 111 microM, respectively.
      Metabolism of AE using human recombinant P450s provided evidence that cytochrome
      P450s 2B6, 3A4, and 3A5 were the primary isozymes responsible for its
      deethylation. CYP3A4 metabolized AE to dihydroqinghaosu at a rate approximately
      10 times that of CYP2B6 and approximately 4.5-fold greater than that of CYP3A5.
      These results demonstrate that CYP3A4 is the primary isozyme involved in the
      metabolism of AE to its active metabolite, DQHS, with secondary contributions by
      CYP2B6 and -3A5.

PMID- 9531518
TI  - Quantitative prediction of the interaction of midazolam and histamine H2 receptor
      antagonists in rats.
AB  - To quantitatively evaluate drug-drug interactions involving metabolic processes
      in the liver, we attempted to predict the increasing ratio of the plasma
      concentration of midazolam (MDZ) in the presence of cimetidine (CIM) or
      nizatidine (NZD) in rats. Under steady-state conditions for the plasma
      concentration of CIM or NZD, MDZ was administered through the portal vein. The
      AUC of MDZ in the presence of CIM was 2.5-fold higher than that in the absence of
      CIM. There was no effect of NZD on the AUC of MDZ. The liver/plasma concentration
      ratios for CIM and NZD were 4.0 and 2.7, respectively. The estimated liver
      unbound concentration (CH,f)/plasma unbound concentration (Cp,f) ratios for CIM
      and NZD were 1.9 and 2.4, respectively, suggesting concentrative hepatic
      accumulation of both drugs. The oxidative metabolism of MDZ in rat liver
      microsomes was competitively inhibited by CIM or NZD, and the Ki values of CIM
      and NZD were 110 and 2600 microM, respectively. Based on these data obtained in
      vivo and in vitro, the increasing ratios for MDZ in the presence of CIM or NZD
      were predicted using the equations Rp = 1 + Cp,f/Ki and RH = 1 + CH,f/Ki. The
      observed increasing ratios in the presence of CIM were very close to RH, compared
      with Rp. However, Cp, f and CH,f were much less than Ki and there was no
      difference between Rp and RH in the presence of NZD. Consequently, Cp,f and CH, f
      were greater than or equal to Ki and Cp,f was not equal to CH,f, as in the
      presence of CIM, and it was indicated that CH,f was more suitable for
      quantitatively predicting the drug-drug interactions than was Cp,f.

PMID- 9531519
TI  - Intracellular and not intraluminal esterolysis of enalapril in kidney. Studies
      with the single pass perfused nonfiltering rat kidney.
AB  - Two possible sites of renal metabolism exist: intracellular, by enzymes within
      the peritubular cells, and intraluminal, by ecto-enzymes embedded on the brush
      border membrane. The esterolysis of enalapril to its dicarboxylate metabolite,
      enalaprilat, was studied in the isolated perfused, nonfiltering rat kidney
      preparation (NFK) and compared with that observed for the isolated perfused rat
      kidney (IPK) to ascertain the site of metabolic conversion. For the NFK,
      filtration was obliterated with the high oncotic pressure (8% bovine serum
      albumin in plasma) and ligation of the ureter, thus preventing enalapril from
      reaching intraluminal sites by filtration. The steady-state renal plasma
      clearance of enalapril in the NFK was 2.0 ml/min/g, a value similar to that (2.1
      ml/min/g) observed previously for the IPK. The rate of appearance of enalaprilat,
      the metabolite, in venous plasma for the NFK (30 +/- 3% of the input rate of
      enalapril) was also comparable with that for the IPK (27 +/- 4%). Further,
      identification of the site of enalapril metabolism (cellular or luminal) was
      aided by simulations based on physiological models and parameters obtained
      previously on the renal handling of enalapril and enalaprilat. These parameters
      were optimized to match closely the experimental observations. The predicted
      total and metabolic renal clearances for the IPK or for the NFK were similar for
      both the "cellular model" and "luminal model": in both instances, values for the
      NFK were 59-65% of those for the IPK. By contrast, predictions for the venous
      output rate of enalaprilat (as a percent of the input rate of enalapril) were
      different: the "cellular model" predicted no change in value between the NFK and
      the IPK, whereas metabolite appearance was greatly magnified for the NFK (289%
      that of the IPK) with luminal metabolism. The lack of difference in venous
      outflow of enalaprilat for the NFK and IPK was more congruent with the notion of
      intracellular and not intraluminal esterolysis of enalapril.

PMID- 9531520
TI  - Stereoselective metabolism of benoxaprofen in rats. Biliary excretion of
      benoxaprofen taurine conjugate and glucuronide.
AB  - Benoxaprofen (BOP) was administered iv to bile duct-cannulated rats at a dose of
      10 mg/kg. BOP and its metabolites in plasma, urine, and bile were quantified
      using HPLC. A previously unidentified BOP metabolite was found in HPLC
      chromatograms of rat bile, and the metabolite was isolated chromatographically.
      Positive-ion fast-atom bombardment (FAB) MS analysis of the compound showed
      [M+H]+ at m/z 409, i.e. 108 mass units greater than the molecular weight of BOP
      (301 mass units). In the 1H NMR spectrum of the compound, two signals assigned to
      two methylene groups appeared at 2.53 ppm and 3. 30 ppm, in addition to BOP
      signals. Analysis of FAB mass spectra and 1H-1H and 1H-13C correlated NMR spectra
      of the isolated metabolite suggested that the new metabolite was a BOP taurine
      conjugate (BOP-T). A BOP-T standard was chemically synthesized, and
      physicochemical data were compared with those for the isolated metabolite.
      Identical results, i.e. RF values from TLC, RT values from HPLC, and FAB MS and
      1H-13C correlated NMR findings, were obtained, establishing that the new
      metabolite found in rat bile was BOP-T. In five rats, mean values for per cent
      excretion of the dose in bile over 12 hr for BOP glucuronide (BOP-G), BOP-T, and
      unchanged BOP were 13.2 +/- 2.3, 2.54 +/- 0.80, and 0.33 +/- 0.09%, respectively.
      Furthermore, the optical isomers of BOP and its metabolites in plasma and bile
      were analyzed using a chiral HPLC column. (R)-BOP showed rapid plasma
      elimination, whereas the plasma elimination of (S)-BOP was very slow. The amounts
      of BOP, BOP-G, and BOP-T enantiomers excreted into the bile were as follows: (S)
      BOP-G and (R)-BOP-G, 12.5 +/- 1.8 and 2.1 +/- 0.6% of the dose; (R)-BOP-T and (S)
      BOP-T, 2.0 +/- 0.6 and 0.3 +/- 0.05% of the dose; (R)-BOP and (S)-BOP, 0.02 +/-
      0.03 and 0.2 +/- 0.1% of the dose, respectively. (S)-BOP was metabolized mainly
      to BOP-G, and BOP-T excreted into the bile was produced mainly from (R)-BOP.

PMID- 9531521
TI  - Dihydralazine-induced inactivation of cytochrome P450 enzymes in rat liver
      microsomes.
AB  - Dihydralazine is known to induce immunoallergic hepatitis, and the anti-liver
      microsome (anti-LM) autoantibodies found in the serum of the patients have been
      reported to react with cytochrome P450 1A2 (CYP1A2). It is thus suggested that a
      reactive metabolite of dihydralazine covalently binds to the P450 protein and
      triggers an immunological response as a neoantigen. We investigated the
      selectivity of inactivation of P450 enzymes during the metabolism of
      dihydralazine to evaluate the target protein of its reactive metabolite. Liver
      microsomes from male Wistar rats were preincubated with dihydralazine in the
      presence of NADPH, followed by assays of several monooxygenase activities.
      Preincubation of microsomes of beta-naphthoflavone-treated rats with
      dihydralazine resulted in time-dependent loss of phenacetin O-deethylase activity
      (an indicator of CYP1A2 activity), showing inactivation of CYP1A2 during the
      dihydralazine metabolism. The preincubation with dihydralazine was less effective
      on ethoxyresorufin O-deethylase activity in microsomes of beta-naphthoflavone
      treated rats (CYP1A1) and pentoxyresorufin O-depentylase activity in microsomes
      of phenobarbital-treated rats (CYP2B). On the other hand, preincubation of
      microsomes of untreated rats with dihydralazine caused time-dependent loss of
      testosterone 2alpha-, 16alpha- (CYP2C11), and 6beta- (CYP3A) hydroxylase
      activities. These results demonstrated that dihydralazine was metabolically
      activated by CYP1A2, and the chemically reactive metabolite bound to the enzyme
      itself and inactivated it, as was suggested by the appearance of anti-LM
      antibodies in dihydralazine-hepatitis, whereas CYP2C and -3A enzymes were also
      suggested to be the enzymes that activate dihydralazine and lead to the target of
      the reactive intermediates.

PMID- 9531522
TI  - Taxol transport by human intestinal epithelial Caco-2 cells.
AB  - Taxol (paclitaxel) belongs to a new class of antimicrotubule anticancer drugs
      with clinical activity against common solid tumors and acute leukemias.
      Preclinical studies have suggested that taxol is not absorbed after oral doses.
      However, whether the observed low oral bioavailability is the result of poor
      absorption or extensive presystemic hepatic metabolism is not clear. For this
      reason, we studied the transepithelial flux of taxol, using the human colonic
      cell line Caco-2 as a model. The cells were grown to confluency on permeable
      polycarbonate membrane inserts, to permit flux experiments after loading of
      [3H]taxol on either the apical or basolateral side. The flux of taxol across the
      Caco-2 cell layer was linear with time for up to 3 hr. The flux from the
      basolateral to the apical side was 4-10 times greater than that from the apical
      to the basolateral side. Whereas the absorptive transport appeared linearly
      related to the taxol concentration (0.5-20 microM), the efflux was saturable. The
      apparent KM of the active efflux component was 16.5 microM. Verapamil (50 microM)
      significantly decreased the active transport component. These data support the
      conclusion that rapid passive diffusion of taxol through the intestinal
      epithelium is partially counteracted by the action of an outwardly directed
      efflux pump, presumably P-glycoprotein. However, the relatively high apparent
      permeability coefficient for the apical to basolateral taxol transport (4.4 +/-
      0.4 x 10(-6) cm/s; N = 17) suggests that the drug may still be effectively
      absorbed in the intestinal tract.

PMID- 9531523
TI  - Biotransformation, tissue distribution, and persistence of 4-nonylphenol residues
      in juvenile rainbow trout (Oncorhynchus mykiss).
AB  - Alkylphenols are weak oestrogenic environmental contaminants and have been
      implicated in the disruption of endocrine function in wildlife. The influence of
      biotransformation, tissue distribution, and elimination on biological activity
      was investigated in juvenile rainbow trout following a single iv dose of [3H]4
      nonylphenol. Distribution and elimination of [3H]4-nonylphenol residues in
      tissues sampled 1, 2, 4, 24, 48, 72, and 144 hr after dosing was determined by
      sample combustion and liquid scintillation counting (LSC). Total 3H-labeled
      residue concentrations in trout 144 hr after dosing were in order: bile >> faeces
      >> liver > pyloric caecae > kidney > brain, gill, gonad, heart, plasma, skeletal
      muscle, and skin. The depletion kinetics of [3H]residues from tissues and plasma
      was biphasic with prolonged beta-phase half-lives in muscle and liver of 99 hr.
      Radio-HPLC analysis of metabolites in bile, liver, pyloric caecae, and faeces
      samples demonstrated similar profiles and contrasted with muscle where only
      parent compound was found. The predominant metabolite in bile was a glucuronide
      conjugate of 4-nonylphenol. Other metabolites included glucuronide conjugates of
      ring or side chain hydroxylated 4-nonylphenol. Liver contained a low level (1.7%)
      of covalently bound residues. Metabolism studies using isolated trout hepatocytes
      produced a similar range of metabolites and a sulfate conjugate of hydroxylated 4
      nonylphenol. Despite rapid metabolism and excretion, a substantial depot of
      parent compound remained in muscle which will have implications for the
      maintenance of 4-nonylphenol residues and associated biological activity.

PMID- 9531525
TI  - Overlapping substrate specificities of cytochrome P450 3A and P-glycoprotein for
      a novel cysteine protease inhibitor.
AB  - K02 (morpholine-urea-Phe-Hphe-vinylsulfone), a newly developed peptidomimetic,
      acts as a potent cysteine protease inhibitor, especially of cathepsins B and L
      (which are associated with cancer progression) and cruzain (a cysteine protease
      of Trypanosoma cruzi, which is responsible for Chagas' disease). Here we
      investigated features of the disposition of K02 using in vitro systems,
      characterizing the interaction of the drug with human cytochrome P450 (CYP) 3A
      and P-glycoprotein (P-gp), a mediator of multidrug resistance (MDR) to cancer
      chemotherapy and a countertransporter in the intestine that limits oral drug
      bioavailability. P-gp functions as an ATP-dependent drug efflux pump to reduce
      intracellular cytotoxic concentrations. An HPLC assay was developed to analyze
      K02 and its metabolites formed in human liver microsomes. Three major primary
      metabolites were determined by LC/MS/MS to be hydroxylated products of the parent
      compound. A rabbit anti-CYP3A polyclonal antibody (200 microl antibody/mg
      microsomal protein) produced 75-94% inhibition of the formation of these three
      hydroxylated metabolites. Ketoconazole (5 microM), a selective CYP3A inhibitor,
      produced up to 75% inhibition, whereas other CYP-specific inhibitors, i.e.
      quinidine (CYP2D6), 7,8-benzoflavone (CYP1A2), and sulfaphenazole (CYP2C9),
      showed no significant effects. An identical metabolite formation profile for K02
      was observed with cDNA-expressed human CYP3A4 (Gentest). These data demonstrate
      that K02 is a substrate for CYP3A. Formation of 1'-hydroxymidazolam, the primary
      human midazolam metabolite, was markedly inhibited by K02 via competitive
      processes, which suggests the potential for drug-drug interactions of K02 with
      other CYP3A substrates. K02 significantly inhibited the photoaffinity labeling of
      P-gp with azidopine and LU-49888, a photoaffinity analogue of verapamil.
      Transport studies with [14C]K02, using MDR1-transfected Madin-Darby canine kidney
      cell monolayers in the Transwell system, demonstrated that the basolateral-to
      apical flux of K02 across MDR1-transfected Madin-Darby canine kidney cells was
      markedly greater than the apical-to-basolateral flux (ratio of 63 with 10 microM
      [14C]K02). This suggests that K02 is also a P-gp substrate. These studies are
      important for formulating strategies to increase the absorption and/or decrease
      the elimination of K02 and to optimize its delivery to malignant cells and
      parasite-infected host cells.

PMID- 9531524
TI  - Paraoxonase has a major role in the hydrolysis of prulifloxacin (NM441), a
      prodrug of a new antibacterial agent.
AB  - NM441 is a prodrug of the new quinolone carboxylic acid antibacterial agent
      NM394. A rat serum enzyme (NM441-hydrolase) that catalyzes the hydrolysis of
      NM441 to NM394 was purified by ultracentrifugation, heparin-Sepharose column
      chromatography, and HPLC with a Mono Q anion exchange column. The enzyme showed a
      single protein band after sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis. Its molecular mass was estimated as 46 kDa. The amino-terminal
      sequence and two internal amino acid sequences of the NM441-hydrolase resemble
      those of mouse, rabbit, and human serum paraoxonases. Moreover, its enzymatic
      characteristics (optimum pH, calcium requirement, and molecular mass) were
      similar to those of the paraoxonases. These findings identify the NM441-hydrolase
      as rat serum paraoxonase. To determine whether the paraoxonase catalyzes the
      hydrolysis of NM441 to NM394 in human serum, we investigated whether the
      paraoxonase and NM441-hydrolase activities were correlated. There was a positive
      correlation (r = 0.653, p < 0.005) found in the sera of 67 healthy volunteers,
      indicating that paraoxonase is responsible for the conversion of NM441 to NM394
      in humans. Human paraoxonase shows polymorphism. There was a 9-fold variation in
      paraoxonase activity but only a 2-fold variation in NM441-hydrolase activity.
      These findings show that paraoxonase polymorphism does not cause marked
      interindividual variation in NM441-hydrolase activity and is substrate dependent.

PMID- 9531526
TI  - Effects of gestational and overt diabetes on human placental cytochromes P450 and
      glutathione S-transferase.
AB  - The placenta possesses the ability to metabolize a number of xenobiotics and
      endogenous compounds by processes similar to those seen in the liver. Animal and
      in vivo studies have observed that the presence of diabetes alters the expression
      of hepatic metabolizing enzymes (cytochrome P450 and glutathione S-transferase);
      however, it is unknown whether similar alterations occur in the human placenta.
      To evaluate whether diabetes has any effect of placental xenobiotic metabolizing
      activity, the catalytic activities of 7-ethoxyresorufin O-deethylation (EROD,
      CYP1A1), chlorzoxazone 6-hydroxylation (CYP2E1), dextromethorphan N-demethylation
      (CYP3A4), dextromethorphan O-demethylation (CYP2D6), and 1-chloro-2, 4
      dinitrobenzene (CDNB) conjugation with glutathione (glutathione S-transferase,
      GST) from placentas of diet (class A1) and insulin-dependent (class A2)
      gestational diabetics and overt diabetics were compared with matched controls.
      EROD activity (CYP1A1) ranged from 0.29 to 2.67 pmol/min/mg protein. However, no
      differences were observed among overt or gestational diabetics and their
      respective matched controls. CDNB conjugation (GST) ranged from 0.275 to 1.65
      units/min/mg protein. In contrast to that observed with CYP1A1, a small but
      statistically significant reduction in GST activity was noted in overt diabetics
      as compared with their matched controls and gestational diabetics. CYP2E1, 2D6,
      and 3A4 enzymatic activities were not detected in human placental tissue. GST
      protein was detectable in all tissues studied, but no CYP protein could be
      detected in any of the tissues. Thus, it seems that pregnant women with overt
      diabetes have reduced GST activity in the placenta, which could potentially
      result in the exposure of the fetus to harmful electrophiles. However, the full
      clinical significance of this finding remains to be elucidated.

PMID- 9531527
TI  - Xenobiotic-enhanced expression of cytochromes P450 2E1 and 2B in primary cultured
      rat hepatocytes.
AB  - Cytochrome P450 2E1 (CYP2E1) and 2B (CYP2B) mRNA and protein expression was
      examined in primary cultured rat hepatocytes under basal cell culture conditions
      and in response to three prototypic CYP2E1 inducers, i.e. ethanol, acetone, and
      pyrazine. Xenobiotic treatment for 24 hr, initiated after hepatocytes had been
      maintained in culture for 72 hr, resulted in 2-8-fold increases in CYP2E1 protein
      levels, relative to untreated cells. A >/=2-fold increase in CYP2E1 protein
      levels was detected at the lowest concentration (1 mM) of each of the xenobiotics
      examined. The increase in CYP2E1 protein expression was not accompanied by any
      significant increase in 2E1 mRNA expression. In contrast, CYP2B protein and mRNA
      levels were increased by acetone or pyrazine at concentrations greater than 1 mM.
      Ethanol (up to 100 mM) failed to significantly increase CYP2B protein or mRNA
      levels. The maximal increases measured for CYP2B protein and mRNA ( approximately
      25-fold and approximately 90-fold, respectively) after treatment of hepatocytes
      with acetone were comparable to those measured in our laboratory, and reported by
      others, for phenobarbital treatment of primary cultured rat hepatocytes. The
      results of this study show that the pattern of expression of CYP2E1 and 2B in
      this primary cultured rat hepatocyte system and the magnitude of induction
      parallel those reported for rat liver in vivo in response to these xenobiotics.
      This primary hepatocyte culture system provides opportunities for studies of the
      role of CYP2E1 in the metabolism and bioactivation of drugs, chemicals, and
      putative carcinogens, as well as mechanistic studies on xenobiotic-mediated
      regulation of CYP2E1 expression.

PMID- 9531528
TI  - Metabolism of dacarbazine by rat liver microsomes contribution of CYP1A enzymes
      to dacarbazine N-demethylation.
AB  - The N-demethylation of dacarbazine in liver microsomes was significantly
      increased by treatment of rats with beta-naphthoflavone, dexamethasone, or
      phenobarbital. However, the extent of increase in the N-demethylation observed in
      beta-naphthoflavone-treated rats was much greater than that observed in
      dexamethasone-treated rats. A good correlation between N-demethylation of
      dacarbazine and O-deethylation of phenacetin was observed when a low
      concentration of phenacetin was used. Furthermore, the activity of dacarbazine N
      demethylase in rat liver microsomes was highly correlated with the amounts of CYP
      protein immunochemically determined with anti-rat CYP1A2 antibodies. In addition,
      antibodies to rat CYP1A2, and furafylline and alpha-naphthoflavone, which are
      known inhibitors of CYP1A enzymes, exhibited inhibitory effects on dacarbazine N
      demethylation. These results indicated that CYP1A enzymes may be responsible for
      N-demethylation of dacarbazine in rat liver microsomes.

PMID- 9531529
TI  - There's the rub: a novel ubiquitin-like modification linked to cell cycle
      regulation.

PMID- 9531530
TI  - EGF domain swap converts a drosophila EGF receptor activator into an inhibitor.
AB  - In Drosophila the function of the epidermal growth factor (EGF) receptor is
      modulated zygotically by three EGF-like proteins: Spitz (Spi), which is a potent
      activator; Vein (Vn), which is a moderate activator; and Argos (Aos), which is an
      inhibitor. Chimeric molecules were constructed in which the EGF domain of Vn was
      swapped with the EGF domain from each factor. The modified Vn proteins behaved
      both in vitro and in vivo with properties characteristic of the factor from which
      the EGF domain was derived. These results demonstrate that the EGF domain is the
      key determinant that gives DER inhibitors and activators their distinct
      properties.

PMID- 9531531
TI  - Modification of yeast Cdc53p by the ubiquitin-related protein rub1p affects
      function of the SCFCdc4 complex.
AB  - The RUB1/NEDD-8 family of ubiquitin-related genes is widely represented among
      eukaryotes. Here we report that Cdc53p in Saccharomyces cerevisiae, a member of
      the Cullin family of proteins, is stably modified by the covalent attachment of a
      single Rub1p molecule. Two genes have been identified that are required for Rub1p
      conjugation to Cdc53p. The first gene, designated ENR2, encodes a protein with
      sequence similarity to the amino-terminal half of the ubiquitin-activating
      enzyme. By analogy with Aos1p, we infer that Enr2p functions in a bipartite Rub1p
      activating enzyme. The second gene is SKP1, shown previously to be required for
      some ubiquitin-conjugation events. A deletion allele of ENR2 is lethal with
      temperature-sensitive alleles of cdc34 and enhances the phenotypes of cdc4,
      cdc53, and skp1, strongly implying that Rub1p conjugation to Cdc53p is required
      for optimal assembly or function of the E3 complex SCFCdc4. Consistent with this
      model, both enr2delta and an allele of Cdc53p that is not Rub1p modified, render
      cells sensitive to alterations in the levels of Cdc4p, Cdc34p, and Cdc53p.

PMID- 9531532
TI  - The fission yeast SPB component Cut12 links bipolar spindle formation to mitotic
      control.
AB  - During fission yeast mitosis, the duplicated spindle pole bodies (SPBs) nucleate
      microtubule arrays that interdigitate to form the mitotic spindle. cut12.1
      mutants form a monopolar mitotic spindle, chromosome segregation fails, and the
      mutant undergoes a lethal cytokinesis. The cut12(+) gene encodes a novel 62-kD
      protein with two predicted coiled coil regions, and one consensus phosphorylation
      site for p34(cdc2) and two for MAP kinase. Cut12 is localized to the SPB
      throughout the cell cycle, predominantly around the inner face of the interphase
      SPB, adjacent to the nucleus. cut12(+) is allelic to stf1(+); stf1.1 is a gain-of
      function mutation bypassing the requirement for the Cdc25 tyrosine phosphatase,
      which normally dephosphorylates and activates the p34(cdc2)/cyclin B kinase to
      promote the onset of mitosis. Expressing a cut12(+) cDNA carrying the stf1.1
      mutation also suppressed cdc25.22. The spindle defect in cut12.1 is exacerbated
      by the cdc25.22 mutation, and stf1.1 cells formed defective spindles in a
      cdc25.22 background at high temperatures. We propose that Cut12 may be a
      regulator or substrate of the p34(cdc2) mitotic kinase.

PMID- 9531534
TI  - Translational readthrough in the hdc mRNA generates a novel branching inhibitor
      in the drosophila trachea.
AB  - A central question in the development of many branched tubular organs, including
      the Drosophila trachea, concerns the mechanisms and molecules that control the
      number and pattern of new branches arising from preexisting vessels. We report on
      a branching inhibitor, Fusion-6 (Fus-6) produced by specialized tracheal cells to
      prevent neighboring cells from branching. In Fus-6 mutants, cells that are
      normally quiescent acquire the branching fate and form an increased number of
      sprouts emanating from the primary branches. Fus-6 is identified as the headcase
      (hdc) gene and is expressed in a subset of the cells that extend fusion sprouts
      to interconnect the tracheal network. hdc expression is regulated by the
      transcription factor escargot (esg) because it is not expressed in the fusion
      cells of esg mutants and is ectopically activated in the trachea in response to
      esg misexpression. We show that the hdc mRNA encodes two overlapping protein
      products by an unusual suppression of translational termination mechanism.
      Translational readthrough is necessary for hdc function because rescue of the
      tracheal mutant phenotype requires the full-length hdc mRNA. In ectopic
      expression experiments with full-length and truncated hdc constructs, only the
      full-length cDNA encoding both proteins could inhibit terminal branching. We
      propose that hdc acts non-autonomously in an inhibitory signaling mechanism to
      determine the number of cells that will form unicellular sprouts in the trachea.

PMID- 9531533
TI  - A CBP/p300 homolog specifies multiple differentiation pathways in Caenorhabditis
      elegans.
AB  - Mammalian p300 and CBP are related transcriptional cofactors that possess histone
      acetyltransferase activity. Inactivation of CBP/p300 is critical for adenovirus
      E1A to induce oncogenic transformation and to inhibit differentiation, suggesting
      that these proteins are likely to play a role in cell growth and differentiation.
      Here we show that a Caenorhabditis elegans gene closely related to CBP/p300,
      referred to as cbp-1, is required during early embryogenesis to specify several
      major differentiation pathways. Inhibition of cbp-1 expression causes
      developmental arrest of C. elegans embryos with no evidence of body morphogenesis
      but with nearly twice the normal complement of embryonic cells. Mesodermal,
      endodermal, and hypodermal cells appear to be completely absent in most embryos,
      however, all of the embryos exhibit evidence of neuronal differentiation. Our
      analysis of this phenotype suggests a critical role for CBP-1 in promoting all
      non-neuronal pathways of somatic differentiation in the C. elegans embryo. In
      contrast, we show that C. elegans genes related to components of a conserved
      mammalian histone deacetylase, appear to have a role in repressing somatic
      differentiation. Our findings suggest a model in which CBP-1 may activate
      transcription and differentiation in C. elegans by directly or indirectly
      antagonizing a repressive effect of histone deacetylase.

PMID- 9531535
TI  - A requirement for NF-kappaB activation in Bcr-Abl-mediated transformation.
AB  - Bcr-Abl is a chimeric oncoprotein that is strongly implicated in acute
      lymphoblastic (ALL) and chronic myelogenous leukemias (CML). This deregulated
      tyrosine kinase selectively causes hematopoietic disorders resembling human
      leukemias in animal models and transforms fibroblasts and hematopoietic cells in
      culture. Bcr-Abl also protects cells from death induced on cytokine deprivation
      or exposure to DNA damaging agents. In addition, the antiapoptotic function of
      Bcr-Abl is thought to play a necessary role in hematopoietic transformation and
      potentially in leukemogenesis. The transcription factor NF-kappaB has been
      identified recently as an inhibitor of apoptosis and as a potential regulator of
      cellular transformation. This study shows that expression of Bcr-Abl leads to
      activation of NF-kappaB-dependent transcription by causing nuclear translocation
      of NF-kappaB as well as by increasing the transactivation function of the
      RelA/p65 subunit of NF-kappaB. Importantly, this activation is dependent on the
      tyrosine kinase activity of Bcr-Abl and partially requires Ras. The ability of
      Bcr-Abl to protect cytokine-dependent 32D myeloid cells from death induced by
      cytokine deprivation or DNA damage does not, however, require functional NF
      kappaB. However, using a super-repressor form of IkappaBalpha, we show that NF
      kappaB is required for Bcr-Abl-mediated tumorigenicity in nude mice and for
      transformation of primary bone marrow cells. This study implicates NF-kappaB as
      an important component of Bcr-Abl signaling. NF-kappaB-regulated genes,
      therefore, likely play a role in transformation by Bcr-Abl and thus in Bcr-Abl
      associated human leukemias.

PMID- 9531536
TI  - CHOP is implicated in programmed cell death in response to impaired function of
      the endoplasmic reticulum.
AB  - Cellular stress, particularly in response to toxic and metabolic insults that
      perturb function of the endoplasmic reticulum (ER stress), is a powerful inducer
      of the transcription factor CHOP. The role of CHOP in the response of cells to
      injury associated with ER stress was examined in a murine deficiency model
      obtained by homologous recombination at the chop gene. Compared with the wild
      type, mouse embryonic fibroblasts (MEFs) derived from chop -/- animals exhibited
      significantly less programmed cell death when challenged with agents that perturb
      ER function. A similar deficit in programmed cells death in response to ER stress
      was also observed in MEFs that lack CHOP's major dimerization partner, C/EBPbeta,
      implicating the CHOP-C/EBP pathway in programmed cell death. An animal model for
      studying the effects of chop on the response to ER stress was developed. It
      entailed exposing mice with defined chop genotypes to a single sublethal
      intraperitoneal injection of tunicamycin and resulted in a severe illness
      characterized by transient renal insufficiency. In chop +/+ and chop +/- mice
      this was associated with the early expression of CHOP in the proximal tubules
      followed by the development of a histological picture similar to the human
      condition known as acute tubular necrosis, a process that resolved by cellular
      regeneration. In the chop -/- animals, in spite of the severe impairment in renal
      function, evidence of cellular death in the kidney was reduced compared with the
      wild type. The proximal tubule epithelium of chop -/- animals exhibited fourfold
      lower levels of TUNEL-positive cells (a marker for programmed cell death), and
      significantly less evidence for subsequent regeneration. CHOP therefore has a
      role in the induction of cell death under conditions associated with malfunction
      of the ER and may also have a role in cellular regeneration under such
      circumstances.

PMID- 9531537
TI  - A coactivator of pre-mRNA splicing.
AB  - The nuclear matrix antigen recognized by the monoclonal antibody (mAb) B1C8 is a
      novel serine (S) and arginine (R)-rich protein associated with splicing complexes
      and is named here SRm160 (SR-related matrix protein of 160 kD). SRm160 contains
      multiple SR repeats, but unlike proteins of the SR family of splicing factors,
      lacks an RNA recognition motif. SRm160 and a related protein SRm300 (the 300-kD
      nuclear matrix antigen recognized by mAb B4A11) form a complex that is required
      for the splicing of specific pre-mRNAs. The SRm160/300 complex associates with
      splicing complexes and promotes splicing through interactions with SR family
      proteins. Binding of SRm160/300 to pre-mRNA is normally also dependent on U1
      snRNP and is stabilized by U2 snRNP. Thus, SRm160/300 forms multiple interactions
      with components bound directly to important sites within pre-mRNA. The results
      suggest that a complex of the nuclear matrix proteins SRm160 and SRm300 functions
      as a coactivator of pre-mRNA splicing.

PMID- 9531538
TI  - Molecular genetic analysis of the heterodimeric splicing factor U2AF: the RS
      domain on either the large or small Drosophila subunit is dispensable in vivo.
AB  - The pre-mRNA splicing factor U2AF (U2 snRNP auxiliary factor) has an essential
      role in 3' splice site selection. U2AF binds the intron pyrimidine tract between
      the branchpoint and the 3' splice site and recruits U2 snRNP to the branch site
      at an early step in spliceosome assembly. Human U2AF is a heterodimer composed of
      large (hU2AF65) and small (hU2AF35) subunits. Both subunits contain a domain
      enriched in arginine-serine dipeptide repeats termed an RS domain. The two U2AF
      RS domains have been assigned essential and independent roles in spliceosome
      assembly in vitro-the hU2AF65 RS domain is required to target U2 snRNP to the
      branch site and the hU2AF35 RS domain is necessary for protein-protein
      interactions with constitutive and alternative splicing factors. We have
      investigated the functional requirements for the RS domains on the Drosophila
      U2AF homolog in vivo. In sharp contrast to its essential role in U2 snRNP
      recruitment in vitro, the RS domain on the Drosophila large subunit homolog
      (dU2AF50) was completely dispensable in vivo. Prompted by this unexpected result,
      we analyzed the RS domain on the Drosophila small subunit homolog (dU2AF38).
      Despite its requirement for enhancer-dependent splicing activity in vitro, the
      dU2AF38 RS domain was also inessential in vivo. Finally, we have tested whether
      the Drosophila U2AF heterodimer requires any RS domain. Flies mutant for both the
      small and large subunits could not be rescued by dU2AF50deltaRS and
      dU2AF38deltaRS transgenes. Therefore, in contrast to the separate roles assigned
      to the U2AF RS domains in vitro, our genetic data suggest that they may have
      redundant functions in vivo.

PMID- 9531540
TI  - Polar localization of the replication origin and terminus in Escherichia coli
      nucleoids during chromosome partitioning.
AB  - We show the intracellular localization of the Escherichia coli replication origin
      (oriC) and chromosome terminus during the cell division cycle by FISH. In newborn
      cells, oriC is localized at the old-pole-proximal nucleoid border and the
      terminus at the new-pole-proximal nucleoid border. One copy of replicated oriC
      migrates rapidly to the opposite nucleoid border. These oriC copies are retained
      at both nucleoid borders, remaining at a constant distance from each cell pole.
      The terminus segment migrates from the nucleoid border to midcell and is retained
      there until the terminus is duplicated. The origin, terminus and other DNA
      regions show three migration patterns during active partitioning of daughter
      chromosomes.

PMID- 9531539
TI  - The guanosine nucleotide (p)ppGpp initiates development and A-factor production
      in myxococcus xanthus.
AB  - Guanosine 3'-di-5'-(tri)di-phosphate nucleotides [(p)ppGpp], synthesized in
      response to amino acid limitation, induce early gene expression leading to
      multicellular fruiting body formation in Myxococcus xanthus. A mutant (DK527)
      that fails to accumulate (p)ppGpp in response to starvation was found to be
      blocked in development prior to aggregation. By use of a series of
      developmentally regulated Tn5lac transcriptional fusion reporters, the time of
      developmental arrest in DK527 was narrowed to within the few hours of
      development, the period of starvation recognition. The mutant is also defective
      in the production of A-factor, an early extracellular cell-density signal. The
      relA gene from Escherichia coli, which encodes a ribosome-dependent (p)ppGpp
      synthetase, rescues this mutant. We also demonstrate that inactivation of the M.
      xanthus relA homolog blocks development and the accumulation of (p)ppGpp.
      Moreover, the wild-type allele of Myxococcus relA rescues DK527. These
      observations support a model in which accumulation of (p)ppGpp, in response to
      starvation, initiates the program of fruiting body development, including the
      production of A-factor.

PMID- 9531541
TI  - Defects in limb, craniofacial, and thymic development in Jagged2 mutant mice.
AB  - The Notch signaling pathway is a conserved intercellular signaling mechanism that
      is essential for proper embryonic development in numerous metazoan organisms. We
      have examined the in vivo role of the Jagged2 (Jag2) gene, which encodes a ligand
      for the Notch family of transmembrane receptors, by making a targeted mutation
      that removes a domain of the Jagged2 protein required for receptor interaction.
      Mice homozygous for this deletion die perinatally because of defects in
      craniofacial morphogenesis. The mutant homozygotes exhibit cleft palate and
      fusion of the tongue with the palatal shelves. The mutant mice also exhibit
      syndactyly (digit fusions) of the fore- and hindlimbs. The apical ectodermal
      ridge (AER) of the limb buds of the mutant homozygotes is hyperplastic, and we
      observe an expanded domain of Fgf8 expression in the AER. In the foot plates of
      the mutant homozygotes, both Bmp2 and Bmp7 expression and apoptotic interdigital
      cell death are reduced. Mutant homozygotes also display defects in thymic
      development, exhibiting altered thymic morphology and impaired differentiation of
      gamma delta lineage T cells. These results demonstrate that Notch signaling
      mediated by Jag2 plays an essential role during limb, craniofacial, and thymic
      development in mice.

PMID- 9531543
TI  - Cell crawling: first the motor, now the transmission.

PMID- 9531542
TI  - A splice variant of CD44 expressed in the apical ectodermal ridge presents
      fibroblast growth factors to limb mesenchyme and is required for limb outgrowth.
AB  - Signals from the apical ectodermal ridge (AER) of the developing vertebrate limb,
      including fibroblast growth factor-8 (FGF-8), can maintain limb mesenchymal cells
      in a proliferative state. We report here that a specific CD44 splice variant is
      crucial for the proliferation of these mesenchymal cells. Epitopes carried by
      this variant colocalize temporally and spatially with FGF-8 in the AER throughout
      early limb development. A splice variant containing the same sequences expressed
      on model cells binds both FGF-4 and FGF-8 and stimulates mesenchymal cells in
      vitro. When applied to the AER, an antibody against a specific CD44 epitope
      blocks FGF presentation and inhibits limb outgrowth. Therefore, CD44 is necessary
      for limb development and functions in a novel growth factor presentation
      mechanism likely relevant in other physiological and pathological situations
      where a cell surface protein presents a signaling molecule to a neighboring cell.

PMID- 9531544
TI  - Homologous chromosome pairing in Drosophila melanogaster proceeds through
      multiple independent initiations.
AB  - The dynamics by which homologous chromosomes pair is currently unknown. Here, we
      use fluorescence in situ hybridization in combination with three-dimensional
      optical microscopy to show that homologous pairing of the somatic chromosome arm
      2L in Drosophila occurs by independent initiation of pairing at discrete loci
      rather than by a processive zippering of sites along the length of chromosome. By
      evaluating the pairing frequencies of 11 loci on chromosome arm 2L over several
      timepoints during Drosophila embryonic development, we show that all 11 loci are
      paired very early in Drosophila development, within 13 h after egg deposition. To
      elucidate whether such pairing occurs by directed or undirected motion, we
      analyzed the pairing kinetics of histone loci during nuclear cycle 14. By
      measuring changes of nuclear length and correlating these changes with
      progression of time during cycle 14, we were able to express the pairing
      frequency and distance between homologous loci as a function of time. Comparing
      the experimentally determined dynamics of pairing to simulations based on
      previously proposed models of pairing motion, we show that the observed pairing
      kinetics are most consistent with a constrained random walk model and not
      consistent with a directed motion model. Thus, we conclude that simple random
      contacts through diffusion could suffice to allow pairing of homologous sites.

PMID- 9531545
TI  - Yeast nuclei display prominent centromere clustering that is reduced in
      nondividing cells and in meiotic prophase.
AB  - Chromosome arrangement in spread nuclei of the budding yeast, Saccharomyces
      cerevisiae was studied by fluorescence in situ hybridization with probes to
      centromeres and telomeric chromosome regions. We found that during interphase
      centromeres are tightly clustered in a peripheral region of the nucleus, whereas
      telomeres tend to occupy the area outside the centromeric domain. In vigorously
      growing cultures, centromere clustering occurred in approximately 90% of cells
      and it appeared to be maintained throughout interphase. It was reduced when cells
      were kept under stationary conditions for an extended period. In meiosis,
      centromere clusters disintegrated before the emergence of the earliest precursors
      of the synaptonemal complex. Evidence for the contribution of centromere
      clustering to other aspects of suprachromosomal nuclear order, in particular the
      vegetative association of homologous chromosomes, is provided, and a possible
      supporting role in meiotic homology searching is discussed.

PMID- 9531546
TI  - Major binding sites for the nuclear import receptor are the internal nucleoporin
      Nup153 and the adjacent nuclear filament protein Tpr.
AB  - A major question in nuclear import concerns the identity of the nucleoporin(s)
      that interact with the nuclear localization sequences (NLS) receptor and its
      cargo as they traverse the nuclear pore. Ligand blotting and solution binding
      studies of isolated proteins have attempted to gain clues to the identities of
      these nucleoporins, but the studies have from necessity probed binding events far
      from an in vivo context. Here we have asked what binding events occur in the more
      physiological context of a Xenopus egg extract, which contains nuclear pore
      subcomplexes in an assembly competent state. We have then assessed our
      conclusions in the context of assembled nuclear pores themselves. We have used
      immunoprecipitation to identify physiologically relevant complexes of
      nucleoporins and importin subunits. In parallel, we have demonstrated that it is
      possible to obtain immunofluorescence localization of nucleoporins to subregions
      of the nuclear pore and its associated structures. By immunoprecipitation, we
      find the nucleoporin Nup153 and the pore-associated filament protein Tpr,
      previously shown to reside at distinct sites on the intranuclear side of
      assembled pores, are each in stable subcomplexes with importin alpha and beta in
      Xenopus egg extracts. Importin subunits are not in stable complexes with
      nucleoporins Nup62, Nup93, Nup98, or Nup214/CAN, either in egg extracts or in
      extracts of assembled nuclear pores. In characterizing the Nup153 complex, we
      find that Nup153 can bind to a complete import complex containing importin alpha,
      beta, and an NLS substrate, consistent with an involvement of this nucleoporin in
      a terminal step of nuclear import. Importin beta binds directly to Nup153 and in
      vitro can do so at multiple sites in the Nup153 FXFG repeat region. Tpr, which
      has no FXFG repeats, binds to importin beta and to importin alpha/beta
      heterodimers, but only to those that do not carry an NLS substrate. That the
      complex of Tpr with importin beta is fundamentally different from that of Nup153
      is additionally demonstrated by the finding that recombinant beta or beta45-462
      fragment freely exchanges with the endogenous importin beta/Nup153 complex, but
      cannot displace endogenous importin beta from a Tpr complex. However, the GTP
      analogue GMP-PNP is able to disassemble both Nup153- and Tpr-importin beta
      complexes. Importantly, analysis of extracts of isolated nuclei indicates that
      Nup153- and Tpr-importin beta complexes exist in assembled nuclear pores. Thus,
      Nup153 and Tpr are major physiological binding sites for importin beta. Models
      for the roles of these interactions are discussed.

PMID- 9531547
TI  - Golgi vesiculation and lysosome dispersion in cells lacking cytoplasmic dynein.
AB  - Cytoplasmic dynein, a minus end-directed, microtubule-based motor protein, is
      thought to drive the movement of membranous organelles and chromosomes. It is a
      massive complex that consists of multiple polypeptides. Among these polypeptides,
      the cytoplasmic dynein heavy chain (cDHC) constitutes the major part of this
      complex. To elucidate the function of cytoplasmic dynein, we have produced mice
      lacking cDHC by gene targeting. cDHC-/- embryos were indistinguishable from
      cDHC+/-or cDHC+/+ littermates at the blastocyst stage. However, no cDHC-/-
      embryos were found at 8.5 d postcoitum. When cDHC-/- blastocysts were cultured in
      vitro, they showed interesting phenotypes. First, the Golgi complex became highly
      vesiculated and distributed throughout the cytoplasm. Second, endosomes and
      lysosomes were not concentrated near the nucleus but were distributed evenly
      throughout the cytoplasm. Interestingly, the Golgi "fragments" and lysosomes were
      still found to be attached to microtubules. These results show that cDHC is
      essential for the formation and positioning of the Golgi complex. Moreover, cDHC
      is required for cell proliferation and proper distribution of endosomes and
      lysosomes. However, molecules other than cDHC might mediate attachment of the
      Golgi complex and endosomes/lysosomes to microtubules.

PMID- 9531548
TI  - Cargo selection by the COPII budding machinery during export from the ER.
AB  - Cargo is selectively exported from the ER in COPII vesicles. To analyze the role
      of COPII in selective transport from the ER, we have purified components of the
      mammalian COPII complex from rat liver cytosol and then analyzed their role in
      cargo selection and ER export. The purified mammalian Sec23-24 complex is
      composed of an 85-kD (Sec23) protein and a 120-kD (Sec24) protein. Although the
      Sec23-24 complex or the monomeric Sec23 subunit were found to be the minimal
      cytosolic components recruited to membranes after the activation of Sar1, the
      addition of the mammalian Sec13-31 complex is required to complete budding. To
      define possible protein interactions between cargo and coat components, we
      recruited either glutathione-S-transferase (GST)-tagged Sar1 or GST- Sec23 to ER
      microsomes. Subsequently, we solubilized and reisolated the tagged subunits using
      glutathione-Sepharose beads to probe for interactions with cargo. We find that
      activated Sar1 in combination with either Sec23 or the Sec23-24 complex is
      necessary and sufficient to recover with high efficiency the type 1 transmembrane
      cargo protein vesicular stomatitis virus glycoprotein in a detergent-soluble
      prebudding protein complex that excludes ER resident proteins. Supplementing
      these minimal cargo recruitment conditions with the mammalian Sec13-31 complex
      leads to export of the selected cargo into COPII vesicles. The ability of cargo
      to interact with a partial COPII coat demonstrates that these proteins initiate
      cargo sorting on the ER membrane before budding and establishes the role of
      GTPase-dependent coat recruitment in cargo selection.

PMID- 9531549
TI  - Pan1p, yeast eps15, functions as a multivalent adaptor that coordinates protein
      protein interactions essential for endocytosis.
AB  - A genetic screen for factors required for endocytosis in the budding yeast
      Saccharomyces cerevisiae previously identified PAN1. Pan1p is a homologue of the
      mammalian protein eps15, which has been implicated in endocytosis by virtue of
      its association with the plasma membrane clathrin adaptor complex AP-2. Pan1p
      contains two eps15 homology (EH) domains, a protein-protein interaction motif
      also present in other proteins that function in membrane trafficking. To address
      the role of Pan1p and EH domains in endocytosis, a yeast two-hybrid screen was
      performed using the EH domain-containing region of Pan1p. This screen identified
      yAP180A, one of two yeast homologues of a class of clathrin assembly proteins
      (AP180) that exhibit in vitro clathrin cage assembly activity. In vitro binding
      studies using GST fusion proteins and yeast extracts defined distinct binding
      sites on yAP180A for Pan1p and clathrin. yAP180 proteins and Pan1p, like actin,
      localize to peripheral patches along the plasma membrane. Mammalian synaptojanin,
      a phosphatidylinositol polyphosphate-5-phosphatase, also has been implicated in
      endocytosis recently, and three synaptojanin-like genes have been identified in
      yeast. We observed genetic interactions between the yeast SJL1 gene and PAN1,
      which suggest a role for phosphoinositide metabolites in Pan1p function. Together
      with other studies, these findings suggest that Pan1p coordinates regulatory
      interactions between proteins required for both endocytosis and actin
      cytoskeleton organization; these proteins include the yAP180 proteins, clathrin,
      the ubiquitin-protein ligase Rsp5p, End3p, and synaptojanin. We suggest that
      Pan1p (and by extension eps15) serves as a multivalent adaptor around which
      dynamic interactions between structural and regulatory components of the
      endocytic pathway converge.

PMID- 9531550
TI  - Dynamin-mediated internalization of caveolae.
AB  - The dynamins comprise an expanding family of ubiquitously expressed 100-kD
      GTPases that have been implicated in severing clathrin-coated pits during
      receptor-mediated endocytosis. Currently, it is unclear whether the different
      dynamin isoforms perform redundant functions or participate in distinct endocytic
      processes. To define the function of dynamin II in mammalian epithelial cells, we
      have generated and characterized peptide-specific antibodies to domains that
      either are unique to this isoform or conserved within the dynamin family. When
      microinjected into cultured hepatocytes these affinity-purified antibodies
      inhibited clathrin-mediated endocytosis and induced the formation of long
      plasmalemmal invaginations with attached clathrin-coated pits. In addition,
      clusters of distinct, nonclathrin-coated, flask-shaped invaginations resembling
      caveolae accumulated at the plasma membrane of antibody-injected cells. In
      support of this, caveola-mediated endocytosis of labeled cholera toxin B was
      inhibited in antibody-injected hepatocytes. Using immunoisolation techniques an
      anti-dynamin antibody isolated caveolar membranes directly from a hepatocyte
      postnuclear membrane fraction. Finally, double label immunofluorescence
      microscopy revealed a striking colocalization between dynamin and the caveolar
      coat protein caveolin. Thus, functional in vivo studies as well as
      ultrastructural and biochemical analyses indicate that dynamin mediates both
      clathrin-dependent endocytosis and the internalization of caveolae in mammalian
      cells.

PMID- 9531551
TI  - Dynamin at the neck of caveolae mediates their budding to form transport vesicles
      by GTP-driven fission from the plasma membrane of endothelium.
AB  - The molecular mechanisms mediating cell surface trafficking of caveolae are
      unknown. Caveolae bud from plasma membranes to form free carrier vesicles through
      a "pinching off" or fission process requiring cytosol and driven by GTP
      hydrolysis (Schnitzer, J.E., P. Oh, and D.P. McIntosh. 1996. Science. 274:239
      242). Here, we use several independent techniques and functional assays ranging
      from cell-free to intact cell systems to establish a function for dynamin in the
      formation of transport vesicles from the endothelial cell plasma membrane by
      mediating fission at the neck of caveolae. This caveolar fission requires
      interaction with cytosolic dynamin as well as its hydrolysis of GTP. Expression
      of dynamin in cytosol as well as purified recombinant dynamin alone supports GTP
      induced caveolar fission in a cell-free assay whereas its removal from cytosol or
      the addition to the cytosol of specific antibodies for dynamin inhibits this
      fission. Overexpression of mutant dynamin lacking normal GTPase activity not only
      inhibits GTP-induced fission and budding of caveolae but also prevents caveolae
      mediated internalization of cholera toxin B chain in intact and permeabilized
      endothelial cells. Analysis of endothelium in vivo by subcellular fractionation
      and immunomicroscopy shows that dynamin is concentrated on caveolae, primarily at
      the expected site of action, their necks. Thus, through its ability to
      oligomerize, dynamin appears to form a structural collar around the neck of
      caveolae that hydrolyzes GTP to mediate internalization via the fission of
      caveolae from the plasma membrane to form free transport vesicles.

PMID- 9531553
TI  - Apical vesicles bearing inositol 1,4,5-trisphosphate receptors in the Ca2+
      initiation site of ductal epithelium of submandibular gland.
AB  - In polarized epithelial cells, agonists trigger Ca2+ waves and oscillations.
      These patterns may be caused by the compartmentalization of inositol 1,4,5
      trisphosphate (IP3)-sensitive Ca2+ pools into specific regions. We have
      investigated the relationship between the distribution of IP3 receptors (IP3Rs)
      and the spatiotemporal pattern of Ca2+ signaling in the duct cells of the rat
      submandibular gland (SMG). Using immunofluorescence, although labeling was
      somewhat heterogeneous, the IP3Rs were colocalized to the apical pole of the duct
      cells. Immunoelectron microscopy identified small apical vesicles bearing IP3R2
      in some types of duct cells. Real-time confocal imaging of intact ducts
      demonstrated that, after carbachol stimulation, an initial Ca2+ spike occurred in
      the apical region. Subsequently, repetitive Ca2+ spikes spread from the apical to
      the middle cytoplasm. These apical Ca2+ initiation sites were found only in some
      "pioneer cells," rather than in all duct cells. We performed both Ca2+ imaging
      and immunofluorescence on the same ducts and detected the strongest immunosignals
      of IP3R2 in the Ca2+ initiation sites of the pioneer cells. The subcellular
      localization and expression level of IP3Rs correlated strongly with the
      spatiotemporal nature of the intracellular Ca2+ signal and distinct Ca2+
      responses among the rat SMG duct cells.

PMID- 9531552
TI  - Apical plasma membrane proteins and endolyn-78 travel through a subapical
      compartment in polarized WIF-B hepatocytes.
AB  - We studied basolateral-to-apical transcytosis of three classes of apical plasma
      membrane (PM) proteins in polarized hepatic WIF-B cells and then compared it to
      the endocytic trafficking of basolaterally recycling membrane proteins. We used
      antibodies to label the basolateral cohort of proteins at the surface of living
      cells and then followed their trafficking at 37 degreesC by indirect
      immunofluorescence. The apical PM proteins aminopeptidase N, 5'nucleotidase, and
      the polymeric IgA receptor were efficiently transcytosed. Delivery to the apical
      PM was confirmed by microinjection of secondary antibodies into the bile
      canalicular-like space and by EM studies. Before acquiring their apical steady
      state distribution, the trafficked antibodies accumulated in a subapical
      compartment, which had a unique tubulovesicular appearance by EM. In contrast,
      antibodies to the receptors for asialoglycoproteins and mannose-6-phosphate or to
      the lysosomal membrane protein, lgp120, distributed to endosomes or lysosomes,
      respectively, without accumulating in the subapical area. However, the route
      taken by the endosomal/lysosomal protein endolyn-78 partially resembled the
      transcytotic pathway, since anti-endolyn-78 antibodies were found in a subapical
      compartment before delivery to lysosomes. Our results suggest that in WIF-B
      cells, transcytotic molecules pass through a subapical compartment that functions
      as a second sorting site for a subset of basolaterally endocytosed membrane
      proteins reaching this compartment.

PMID- 9531554
TI  - The 13-kD FK506 binding protein, FKBP13, interacts with a novel homologue of the
      erythrocyte membrane cytoskeletal protein 4.1.
AB  - We have identified a novel generally expressed homologue of the erythrocyte
      membrane cytoskeletal protein 4.1, named 4.1G, based on the interaction of its
      COOH-terminal domain (CTD) with the immunophilin FKBP13. The 129-amino acid
      peptide, designated 4.1G-CTD, is the first known physiologic binding target of
      FKBP13. FKBP13 is a 13-kD protein originally identified by its high affinity
      binding to the immunosuppressant drugs FK506 and rapamycin (Jin, Y., M.W. Albers,
      W.S. Lane, B.E. Bierer, and S.J. Burakoff. 1991. Proc. Natl. Acad. Sci. USA.
      88:6677- 6681); it is a membrane-associated protein thought to function as an ER
      chaperone (Bush, K.T., B.A. Henrickson, and S.K. Nigam. 1994. Biochem. J.
      [Tokyo]. 303:705-708). We report the specific association of FKBP13 with 4.1G-CTD
      based on yeast two-hybrid, in vitro binding and coimmunoprecipitation
      experiments. The histidyl-proline moiety of 4.1G-CTD is required for FKBP13
      binding, as indicated by yeast experiments with truncated and mutated 4.1G-CTD
      constructs. In situ hybridization studies reveal cellular colocalizations for
      FKBP13 and 4.1G-CTD throughout the body during development, supporting a
      physiologic role for the interaction. Interestingly, FKBP13 cofractionates with
      the red blood cell homologue of 4.1 (4.1R) in ghosts, inside-out vesicles, and
      Triton shell preparations. The identification of FKBP13 in erythrocytes, which
      lack ER, suggests that FKBP13 may additionally function as a component of
      membrane cytoskeletal scaffolds.

PMID- 9531555
TI  - Three-dimensional structure of Acanthamoeba castellanii myosin-IB (MIB)
      determined by cryoelectron microscopy of decorated actin filaments.
AB  - The Acanthamoeba castellanii myosin-Is were the first unconventional myosins to
      be discovered, and the myosin-I class has since been found to be one of the more
      diverse and abundant classes of the myosin superfamily. We used two-dimensional
      (2D) crystallization on phospholipid monolayers and negative stain electron
      microscopy to calculate a projection map of a "classical" myosin-I, Acanthamoeba
      myosin-IB (MIB), at approximately 18 A resolution. Interpretation of the
      projection map suggests that the MIB molecules sit upright on the membrane. We
      also used cryoelectron microscopy and helical image analysis to determine the
      three-dimensional structure of actin filaments decorated with unphosphorylated
      (inactive) MIB. The catalytic domain is similar to that of other myosins, whereas
      the large carboxy-terminal tail domain differs greatly from brush border myosin-I
      (BBM-I), another member of the myosin-I class. These differences may be relevant
      to the distinct cellular functions of these two types of myosin-I. The catalytic
      domain of MIB also attaches to F-actin at a significantly different angle,
      approximately 10 degrees, than BBM-I. Finally, there is evidence that the tails
      of adjacent MIB molecules interact in both the 2D crystal and in the decorated
      actin filaments.

PMID- 9531556
TI  - Pericentrin and gamma-tubulin form a protein complex and are organized into a
      novel lattice at the centrosome.
AB  - Pericentrin and gamma-tubulin are integral centrosome proteins that play a role
      in microtubule nucleation and organization. In this study, we examined the
      relationship between these proteins in the cytoplasm and at the centrosome. In
      extracts prepared from Xenopus eggs, the proteins were part of a large complex as
      demonstrated by sucrose gradient sedimentation, gel filtration and
      coimmunoprecipitation analysis. The pericentrin-gamma-tubulin complex was
      distinct from the previously described gamma-tubulin ring complex (gamma-TuRC) as
      purified gamma-TuRC fractions did not contain detectable pericentrin. When
      assembled at the centrosome, the two proteins remained in close proximity as
      shown by fluorescence resonance energy transfer. The three- dimensional
      organization of the centrosome-associated fraction of these proteins was
      determined using an improved immunofluorescence method. This analysis revealed a
      novel reticular lattice that was conserved from mammals to amphibians, and was
      organized independent of centrioles. The lattice changed dramatically during the
      cell cycle, enlarging from G1 until mitosis, then rapidly disassembling as cells
      exited mitosis. In cells colabeled to detect centrosomes and nucleated
      microtubules, lattice elements appeared to contact the minus ends of nucleated
      microtubules. Our results indicate that pericentrin and gamma-tubulin assemble
      into a unique centrosome lattice that represents the higher-order organization of
      microtubule nucleating sites at the centrosome.

PMID- 9531557
TI  - Rho guanosine triphosphatase mediates the selective stabilization of microtubules
      induced by lysophosphatidic acid.
AB  - The asymmetric distribution of stable, posttranslationally modified microtubules
      (MTs) contributes to the polarization of many cell types, yet the factors
      controlling the formation of these MTs are not known. We have found that
      lysophosphatidic acid (LPA) is a major serum factor responsible for rapidly
      generating stable, detyrosinated (Glu) MTs in serum-starved 3T3 cells. Using C3
      toxin and val14 rho we showed that rho was both necessary and sufficient for the
      induction of Glu MTs by LPA and serum. Unlike previously described factors that
      induce MT stability, rho induced the stabilization of only a subset of the MTs
      and, in wound-edge cells, these stable MTs were appropriately oriented toward the
      leading edge of the cell. LPA had little effect on individual parameters of MT
      dynamics, but did induce long states of pause in a subset of MTs near the edge of
      the cell. Rho stimulation of MT stability was independent of actin stress fiber
      formation. These results identify rho as a novel regulator of the MT cytoskeleton
      that selectively stabilizes MTs during cell polarization by acting as a switch
      between dynamic and stable states of MTs rather than as a modulator of MT
      assembly and disassembly.

PMID- 9531558
TI  - A new member of the Rho family, Rnd1, promotes disassembly of actin filament
      structures and loss of cell adhesion.
AB  - Members of the Rho GTPase family regulate the organization of the actin
      cytoskeleton in response to extracellular growth factors. We have identified
      three proteins that form a distinct branch of the Rho family: Rnd1, expressed
      mostly in brain and liver; Rnd2, highly expressed in testis; and Rnd3/RhoE,
      showing a ubiquitous low expression. At the subcellular level, Rnd1 is
      concentrated at adherens junctions both in confluent fibroblasts and in
      epithelial cells. Rnd1 has a low affinity for GDP and spontaneously exchanges
      nucleotide rapidly in a physiological buffer. Furthermore, Rnd1 lacks intrinsic
      GTPase activity suggesting that in vivo, it might be constitutively in a GTP
      bound form. Expression of Rnd1 or Rnd3/RhoE in fibroblasts inhibits the formation
      of actin stress fibers, membrane ruffles, and integrin-based focal adhesions and
      induces loss of cell-substrate adhesion leading to cell rounding (hence Rnd for
      "round"). We suggest that these proteins control rearrangements of the actin
      cytoskeleton and changes in cell adhesion.

PMID- 9531559
TI  - ZO-3, a novel member of the MAGUK protein family found at the tight junction,
      interacts with ZO-1 and occludin.
AB  - A 130-kD protein that coimmunoprecipitates with the tight junction protein ZO-1
      was bulk purified from Madin-Darby canine kidney (MDCK) cells and subjected to
      partial endopeptidase digestion and amino acid sequencing. A resulting 19-amino
      acid sequence provided the basis for screening canine cDNA libraries. Five
      overlapping clones contained a single open reading frame of 2,694 bp coding for a
      protein of 898 amino acids with a predicted molecular mass of 98,414 daltons.
      Sequence analysis showed that this protein contains three PSD-95/SAP90, discs
      large, ZO-1 (PDZ) domains, a src homology (SH3) domain, and a region similar to
      guanylate kinase, making it homologous to ZO-1, ZO-2, the discs large tumor
      suppressor gene product of Drosophila, and other members of the MAGUK family of
      proteins. Like ZO-1 and ZO-2, the novel protein contains a COOH-terminal acidic
      domain and a basic region between the first and second PDZ domains. Unlike ZO-1
      and ZO-2, this protein displays a proline-rich region between PDZ2 and PDZ3 and
      apparently contains no alternatively spliced domain. MDCK cells stably
      transfected with an epitope-tagged construct expressed the exogenous polypeptide
      at an apparent molecular mass of approximately 130 kD. Moreover, this protein
      colocalized with ZO-1 at tight junctions by immunofluorescence and immunoelectron
      microscopy. In vitro affinity analyses demonstrated that recombinant 130-kD
      protein directly interacts with ZO-1 and the cytoplasmic domain of occludin, but
      not with ZO-2. We propose that this protein be named ZO-3.

PMID- 9531560
TI  - Linking integrin alpha6beta4-based cell adhesion to the intermediate filament
      cytoskeleton: direct interaction between the beta4 subunit and plectin at
      multiple molecular sites.
AB  - Recent studies with patients suffering from epidermolysis bullosa simplex
      associated with muscular dystrophy and the targeted gene disruption in mice
      suggested that plectin, a versatile cytoskeletal linker and intermediate filament
      binding protein, may play an essential role in hemidesmosome integrity and
      stabilization. To define plectin's interactions with hemidesmosomal proteins on
      the molecular level, we studied its interaction with the uniquely long
      cytoplasmic tail domain of the beta4 subunit of the basement membrane laminin
      receptor integrin alpha6beta4 that has been implicated in connecting the
      transmembrane integrin complex with hemidesmosome-anchored cytokeratin filaments.
      In vitro binding and in vivo cotransfection assays, using recombinant mutant
      forms of both proteins, revealed their direct interaction via multiple molecular
      domains. Furthermore, we show in vitro self-interaction of integrin beta4
      cytoplasmic domains, as well as disruption of intermediate filament network
      arrays and dislocation of hemidesmosome-associated endogenous plectin upon
      ectopic overexpression of this domain in PtK2 and/or 804G cells. The close
      association of plectin molecules with hemidesmosomal structures and their
      apparent random orientation was indicated by gold immunoelectron microscopy using
      domain-specific antibodies. Our data support a model in which plectin stabilizes
      hemidesmosomes, via directly interlinking integrin beta4 subunits and cytokeratin
      filaments.

PMID- 9531561
TI  - The Ig superfamily cell adhesion molecule, apCAM, mediates growth cone steering
      by substrate-cytoskeletal coupling.
AB  - Dynamic cytoskeletal rearrangements are involved in neuronal growth cone motility
      and guidance. To investigate how cell surface receptors translate guidance cue
      recognition into these cytoskeletal changes, we developed a novel in vitro assay
      where beads, coated with antibodies to the immunoglobulin superfamily cell
      adhesion molecule apCAM or with purified native apCAM, replaced cellular
      substrates. These beads associated with retrograde F-actin flow, but in contrast
      to previous studies, were then physically restrained with a microneedle to
      simulate interactions with noncompliant cellular substrates. After a latency
      period of approximately 10 min, we observed an abrupt increase in bead
      restraining tension accompanied by direct extension of the microtubule-rich
      central domain toward sites of apCAM bead binding. Most importantly, we found
      that retrograde F-actin flow was attenuated only after restraining tension had
      increased and only in the bead interaction axis where preferential microtubule
      extension occurred. These cytoskeletal and structural changes are very similar to
      those reported for growth cone interactions with physiological targets.
      Immunolocalization using an antibody against the cytoplasmic domain of apCAM
      revealed accumulation of the transmembrane isoform of apCAM around bead-binding
      sites. Our results provide direct evidence for a mechanical continuum from apCAM
      bead substrates through the peripheral domain to the central cytoplasmic domain.
      By modulating functional linkage to the underlying actin cytoskeleton, cell
      surface receptors such as apCAM appear to enable the application of tensioning
      forces to extracellular substrates, providing a mechanism for transducing
      retrograde flow into guided growth cone movement.

PMID- 9531562
TI  - Activation of distinct alpha5beta1-mediated signaling pathways by fibronectin's
      cell adhesion and matrix assembly domains.
AB  - The interaction of cells with fibronectin generates a series of complex signaling
      events that serve to regulate several aspects of cell behavior, including growth,
      differentiation, adhesion, and motility. The formation of a fibronectin matrix is
      a dynamic, cell-mediated process that involves both ligation of the alpha5beta1
      integrin with the Arg-Gly-Asp (RGD) sequence in fibronectin and binding of the
      amino terminus of fibronectin to cell surface receptors, termed "matrix assembly
      sites," which mediate the assembly of soluble fibronectin into insoluble fibrils.
      Our data demonstrate that the amino-terminal type I repeats of fibronectin bind
      to the alpha5beta1 integrin and support cell adhesion. Furthermore, the amino
      terminus of fibronectin modulates actin assembly, focal contact formation,
      tyrosine kinase activity, and cell migration. Amino-terminal fibronectin
      fragments and RGD peptides were able to cross-compete for binding to the
      alpha5beta1 integrin, suggesting that these two domains of fibronectin cannot
      bind to the alpha5beta1 integrin simultaneously. Cell adhesion to the amino
      terminal domain of fibronectin was enhanced by cytochalasin D, suggesting that
      the ligand specificity of the alpha5beta1 integrin is regulated by the
      cytoskeleton. These data suggest a new paradigm for integrin-mediated signaling,
      where distinct regions within one ligand can modulate outside-in signaling
      through the same integrin.

PMID- 9531563
TI  - Processing of laminin-5 and its functional consequences: role of plasmin and
      tissue-type plasminogen activator.
AB  - The laminin-5 component of the extracellular matrices of certain cultured cells
      such as the rat epithelial cell line 804G and the human breast epithelial cell
      MCF-10A is capable of nucleating assembly of cell- matrix adhesive devices called
      hemidesmosomes when other cells are plated upon them. These matrices also impede
      cell motility. In contrast, cells plated onto the laminin-5-rich matrices of
      pp126 epithelial cells fail to assemble hemidesmosomes and are motile. To
      understand these contradictory phenomena, we have compared the forms of
      heterotrimeric laminin-5 secreted by 804G and MCF-10A cells with those secreted
      by pp126 cells, using a panel of laminin-5 subunit-specific antibodies. The
      alpha3 subunit of laminin-5 secreted by pp126 cells migrates at 190 kD, whereas
      that secreted by 804G and MCF-10A cells migrates at 160 kD. The pp126 cell 190-kD
      alpha3 chain of laminin-5 can be specifically proteolyzed by plasmin to a 160-kD
      species at enzyme concentrations that do not apparently effect the laminin-5 beta
      and gamma chains. After plasmin treatment, pp126 cell laminin-5 not only impedes
      cell motility but also becomes competent to nucleate assembly of hemidesmosomes.
      The possibility that plasmin may play an important role in processing laminin-5
      subunits is supported by immunofluorescence analyses that demonstrate
      colocalization of laminin-5 and plasminogen in the extracellular matrix of MCF
      10A and pp126 cells. Whereas tissue-type plasminogen activator (tPA), which
      converts plasminogen to plasmin, codistributes with laminin-5 in MCF-10A matrix,
      tPA is not present in pp126 extracellular matrix. Treatment of pp126 laminin-5
      rich extracellular matrix with exogenous tPA results in proteolysis of the
      laminin-5 alpha3 chain from 190 to 160 kD. In addition, plasminogen and tPA bind
      laminin-5 in vitro. In summary, we provide evidence that laminin-5 is a
      multifunctional protein that can act under certain circumstances as a motility
      and at other times as an adhesive factor. In cells in culture, this functional
      conversion appears dependent upon and is regulated by tPA and plasminogen.

PMID- 9531564
TI  - Association between the rat homologue of CO-029, a metastasis-associated
      tetraspanin molecule and consumption coagulopathy.
AB  - Recently, we have described a panel of metastasis-associated antigens in the rat,
      i.e., of molecules expressed on metastasizing, but not on nonmetastasizing tumor
      lines. One of these molecules, recognized by the monoclonal antibody D6.1 and
      named accordingly D6. 1A, was found to be abundantly expressed predominantly on
      mesenchyme-derived cells. The DNA of the antigen has been isolated and cloned.
      Surprisingly, the gene product proved to interfere strongly with coagulation. The
      1.182-kb cDNA codes for a 235-amino acid long molecule with a 74.2% homology in
      the nucleotide and a 70% homology in the amino acid sequence to CO-029, a human
      tumor-associated molecule. According to the distribution of hydrophobic and
      hydrophilic amino acids, D6.1A belongs to the tetraspanin superfamily. Western
      blotting of D6.1A-positive metastasizing tumor lines revealed that the D6.1A,
      like many tetraspanin molecules, is linked to further membrane molecules, one of
      which could be identified as alpha6beta1 integrin. Transfection of a low
      metastasizing tumor cell line with D6.1A cDNA resulted in increased metastatic
      potential and provided a clue as to the functional role of D6.1A. We noted
      massive bleeding around the metastases and, possibly as a consequence, local
      infarctions predominantly in the mesenteric region and all signs of a consumption
      coagulopathy. By application of the D6.1 antibody the coagulopathy was
      counterregulated, though not prevented. It has been known for many years that
      tumor growth and progression is frequently accompanied by thrombotic disorders.
      Our data suggest that the phenomenon could well be associated with the expression
      of tetraspanin molecules.

PMID- 9531565
TI  - The tyrosine kinase p56lck mediates activation of swelling-induced chloride
      channels in lymphocytes.
AB  - Osmotic cell swelling activates Cl- channels to achieve anion efflux. In this
      study, we find that both the tyrosine kinase inhibitor herbimycin A and genetic
      knockout of p56lck, a src-like tyrosine kinase, block regulatory volume decrease
      (RVD) in a human T cell line. Activation of a swelling-activated chloride current
      (ICl-swell) by osmotic swelling in whole-cell patch-clamp experiments is blocked
      by herbimycin A and lavendustin. Osmotic activation of ICl-swell is defective in
      p56lck-deficient cells. Retransfection of p56lck restores osmotic current
      activation. Furthermore, tyrosine kinase activity is sufficient for activation of
      ICl-swell. Addition of purified p56lck to excised patches activates an outwardly
      rectifying chloride channel with 31 pS unitary conductance. Purified p56lck
      washed into the cytoplasm activates ICl-swell in native and p56lck-deficient
      cells even when hypotonic intracellular solutions lead to cell shrinkage. When
      whole-cell currents are activated either by swelling or by p56lck, slow single
      channel gating events can be observed revealing a unitary conductance of 25-28
      pS. In accordance with our patch-clamp data, osmotic swelling increases activity
      of immunoprecipitated p56lck. We conclude that osmotic swelling activates ICl
      swell in lymphocytes via the tyrosine kinase p56lck.

PMID- 9531568
TI  - Hypothesis: ceramide conditionally activates atypical protein kinases C, Raf-1
      and KSR through binding to their cysteine-rich domains.

PMID- 9531567
TI  - A putative catenin-cadherin system mediates morphogenesis of the Caenorhabditis
      elegans embryo.
AB  - During morphogenesis of the Caenorhabditis elegans embryo, hypodermal (or
      epidermal) cells migrate to enclose the embryo in an epithelium and,
      subsequently, change shape coordinately to elongate the body (Priess, J.R., and
      D.I. Hirsh. 1986. Dev. Biol. 117:156- 173; Williams-Masson, E.M., A.N. Malik, and
      J. Hardin. 1997. Development [Camb.]. 124:2889-2901). We have isolated mutants
      defective in morphogenesis that identify three genes required for both cell
      migration during body enclosure and cell shape change during body elongation.
      Analyses of hmp-1, hmp-2, and hmr-1 mutants suggest that products of these genes
      anchor contractile actin filament bundles at the adherens junctions between
      hypodermal cells and, thereby, transmit the force of bundle contraction into cell
      shape change. The protein products of all three genes localize to hypodermal
      adherens junctions in embryos. The sequences of the predicted HMP-1, HMP-2, and
      HMR-1 proteins are related to the cell adhesion proteins alpha-catenin, beta
      catenin/Armadillo, and classical cadherin, respectively. This putative catenin
      cadherin system is not essential for general cell adhesion in the C. elegans
      embryo, but rather mediates specific aspects of morphogenetic cell shape change
      and cytoskeletal organization.

PMID- 9531566
TI  - Dynamic interaction of PTPmu with multiple cadherins in vivo.
AB  - There is a growing body of evidence to implicate reversible tyrosine
      phosphorylation as an important mechanism in the control of the adhesive function
      of cadherins. We previously demonstrated that the receptor protein tyrosine
      phosphatase PTPmu associates with the cadherin-catenin complex in various tissues
      and cells and, therefore, may be a component of such a regulatory mechanism
      (Brady-Kalnay, S. M., D.L. Rimm, and N.K. Tonks. 1995. J. Cell Biol. 130:977-
      986). In this study, we present further characterization of this interaction
      using a variety of systems. We observed that PTPmu interacted with N-cadherin, E
      cadherin, and cadherin-4 (also called R-cadherin) in extracts of rat lung. We
      observed a direct interaction between PTPmu and E-cadherin after coexpression in
      Sf9 cells. In WC5 cells, which express a temperature-sensitive mutant form of v
      Src, the complex between PTPmu and E-cadherin was dynamic, and conditions that
      resulted in tyrosine phosphorylation of E-cadherin were associated with
      dissociation of PTPmu from the complex. Furthermore, we have demonstrated that
      the COOH-terminal 38 residues of the cytoplasmic segment of E-cadherin was
      required for association with PTPmu in WC5 cells. Zondag et al. (Zondag, G., W.
      Moolenaar, and M. Gebbink. 1996. J. Cell Biol. 134: 1513-1517) have asserted that
      the association we observed between PTPmu and the cadherin-catenin complex in
      immunoprecipitates of the phosphatase arises from nonspecific cross-reactivity
      between BK2, our antibody to PTPmu, and cadherins. In this study we have
      confirmed our initial observation and demonstrated the presence of cadherin in
      immunoprecipitates of PTPmu obtained with three antibodies that recognize
      distinct epitopes in the phosphatase. In addition, we have demonstrated directly
      that the anti-PTPmu antibody BK2 that we used initially did not cross-react with
      cadherin. Our data reinforce the observation of an interaction between PTPmu and
      E-cadherin in vitro and in vivo, further emphasizing the potential importance of
      reversible tyrosine phosphorylation in regulating cadherin function.

PMID- 9531569
TI  - Acute promyelocytic leukemia: relieving repression induces remission.

PMID- 9531570
TI  - Reduced retinoic acid-sensitivities of nuclear receptor corepressor binding to
      PML- and PLZF-RARalpha underlie molecular pathogenesis and treatment of acute
      promyelocytic leukemia.
AB  - Typical acute promyelocytic leukemia (APL) is associated with expression of the
      PML-RARalpha fusion protein and responsiveness to treatment with all-trans
      retinoic acid (ATRA). A rare, but recurrent, APL has been described that does not
      respond to ATRA treatment and is associated with a variant chromosomal
      translocation and expression of the PLZF-RARalpha fusion protein. Both PML- and
      PLZF-RARalpha possess identical RAR sequences and inhibit ATRA-induced gene
      transcription as well as cell differentiation. We now show that the above
      mentioned oncogenic fusion proteins interact with the nuclear receptor
      corepressor N-CoR and, in comparison with the wild-type RARalpha protein, their
      interactions display reduced sensitivities to ATRA. Although pharmacologic
      concentration of ATRA could still induce dissociation of N-CoR from PML-RARalpha,
      it had a very little effect on its association with the PLZF-RARalpha fusion
      protein. This ATRA-insensitive interaction between N-CoR and PLZF-RARalpha was
      mediated by the N-terminal PLZF moiety of the chimera. It appears that N
      CoR/histone deacetylase corepressor complex interacts directly in an ATRA
      insensitive manner with the BTB/POZ-domain of the wild-type PLZF protein and is
      required, at least in part, for its function as a transcriptional repressor. As
      the above-noted results predict, histone deacetylase inhibitors antagonize
      oncogenic activities of the PML-RARalpha fusion protein and partially relieve
      transcriptional repression by PLZF as well as inhibitory effect of PLZF-RARalpha
      on ATRA response. Taken together, our results demonstrate involvement of nuclear
      receptor corepressor/histone deacetylase complex in the molecular pathogenesis of
      APL and provide an explanation for differential sensitivities of PML- and PLZF
      RARalpha-associated leukemias to ATRA.

PMID- 9531571
TI  - An electronic database of human hemoglobin variants on the World Wide Web.

PMID- 9531572
TI  - Integrin signaling: the platelet paradigm.

PMID- 9531573
TI  - Apoptotic signal of Fas is not mediated by ceramide.
AB  - Ceramide has been suggested as the secondary messenger mediating the apoptotic
      signal for Fas engagement. By using different inhibitors, we demonstrated here
      that ceramide is unlikely a mediator of Fas-initiated apoptosis. First, cAMP
      prevented cell death induced by ceramide but not by Fas. Second, ceramide
      triggered, but not Fas-triggered, apoptosis was antagonized by the free radical
      scavenger C60. Third, the metal chelator pyrrolidinedithiocarbamate suppressed
      ceramide-initiated DNA fragmentation but had no effect on the Fas-induced cell
      death. Fourth, the SAPK/ERK kinase dominant negative mutant, which attenuated
      ceramide-induced cell death, did not prevent Fas-induced apoptosis. Finally,
      activation of NF-kappaB inhibited ceramide-induced but not Fas-initiated
      apoptosis. The fact that many antagonists of ceramide-induced apoptosis could not
      suppress Fas-mediated cell death clearly indicates that ceramide is not the
      mediator for Fas-initiated apoptotic signal.

PMID- 9531574
TI  - An in vitro model of human red blood cell production from hematopoietic
      progenitor cells.
AB  - Hemoglobinopathies, such as beta-thalassemias and sickle cell anemia (SCA), are
      among the most common inherited gene defects. Novel models of human
      erythropoiesis that result in terminally differentiated red blood cells (RBCs)
      would be able to address the pathophysiological abnormalities in erythrocytes in
      congenital RBC disorders and to test the potential of reversing these problems by
      gene therapy. We have developed an in vitro model of production of human RBCs
      from normal CD34(+) hematopoietic progenitor cells, using recombinant growth
      factors to promote terminal RBC differentiation. Enucleated RBCs were then
      isolated to a pure population by flow cytometry in sufficient numbers for
      physiological studies. Morphologically, the RBCs derived in vitro ranged from
      early polylobulated forms, resembling normal reticulocytes to smooth biconcave
      discocytes. The hemoglobin pattern in the in vitro-derived RBCs mimicked the in
      vivo adult or postnatal pattern of beta-globin production, with negligible gamma
      globin synthesis. To test the gene therapy potential using this model, CD34(+)
      cells were genetically marked with a retroviral vector carrying a cell-surface
      reporter. Gene transfer into CD34(+) cells followed by erythroid differentiation
      resulted in expression of the marker gene on the surface of the enucleated RBC
      progeny. This model of human erythropoiesis will allow studies on pathophysiology
      of congenital RBC disorders and test effective therapeutic strategies.

PMID- 9531575
TI  - Human immunodeficiency virus-1 infection interrupts thymopoiesis and multilineage
      hematopoiesis in vivo.
AB  - It is still uncertain whether multilineage hematopoietic progenitor cells are
      affected by human immunodeficiency virus-1 (HIV-1) infection in vivo. The SCID-hu
      Thy/Liv model is permissive of long-term multilineage human hematopoiesis,
      including T lymphopoiesis. This model was used to investigate the effects of HIV
      1 infection on early hematopoietic progenitor function. We found that both
      lineage-restricted and multilineage hematopoietic progenitors were depleted from
      grafts infected with either a molecular clone or a primary isolate of HIV-1.
      Depletion of hematopoietic progenitors (including CD34(+) cells, colony-forming
      units in methylcellulose, and long-term culture-initiating cells) occurred
      several days before the onset of thymocyte depletion, indicating that the
      subsequent rapid decline in thymocyte numbers was due at least in part to loss of
      thymocyte progenitors. HIV-1 proviral genomes were not detected at high frequency
      in hematopoietic cells earlier than the intrathymic T-progenitor cell stage,
      despite the depletion of such cells in infected grafts. Proviral genomes were
      also not detected in colonies derived from progenitor cells from infected grafts.
      These data demonstrate that HIV-1 infection interrupts both lineage-restricted
      and multilineage hematopoiesis in vivo and suggest that depletion of early
      hematopoietic progenitor cells occurs in the absence of direct viral infection.

PMID- 9531576
TI  - Syndecan-1 is a multifunctional regulator of myeloma pathobiology: control of
      tumor cell survival, growth, and bone cell differentiation.
AB  - Multiple myeloma is characterized by an accumulation of malignant plasma cells in
      the bone marrow coupled with an altered balance of osteoclasts and osteoblasts,
      leading to lytic bone disease. Although some of the cytokines driving this
      process have been characterized, little is known about the negative regulators.
      We show that syndecan-1 (CD 138), a heparan sulfate proteoglycan, expressed on
      and actively shed from the surface of most myeloma cells, induces apoptosis and
      inhibits the growth of myeloma tumor cells and also mediates decreased osteoclast
      and increased osteoblast differentiation. The addition of intact purified
      syndecan-1 ectodomain (1 to 6 nmol/L) to myeloma cell lines in culture leads to
      induction of apoptosis and dose-dependent growth inhibition, with concurrent
      downregulation of cyclin D1. The addition of purified syndecan-1 in picomolar
      concentrations to bone marrow cells in culture leads to a dose-dependent decrease
      in osteoclastogenesis and a smaller increase in osteoblastogenesis. In contrast
      to the effect on myeloma cells, the effect of syndecan-1 on osteoclastogenesis
      only requires the syndecan-1 heparan sulfate chains and not the intact
      ectodomain, suggesting that syndecan's effect on myeloma and bone cells occurs
      through different mechanisms. When injected in severe combined immune deficient
      (scid) mice, control-transfected myeloma cells (ARH-77 cells) expressing little
      syndecan-1 readily form tumors, leading to hind limb paralysis and lytic bone
      disease. However, after the injection of syndecan-1-transfected ARH-77 cells, the
      development of disease-related morbidity and lytic bone disease is significantly
      inhibited. Taken together, our data demonstrate, both in vitro and in vivo, that
      syndecan-1 has a significant beneficial effect on the behavior of both myeloma
      and bone cells and therefore may represent one of the central molecules in the
      regulation of myeloma pathobiology.

PMID- 9531577
TI  - Chronic lymphocytic leukemia B cells can express CD40 ligand and demonstrate T
      cell type costimulatory capacity.
AB  - Chronic lymphocytic leukemia (CLL) is characterized by a clonal expansion of
      CD5(+) B cells in the peripheral blood. Associated immune aberrations include
      abnormal Th-cell function and pathogenic autoantibodies. Under most
      circumstances, CLL B cells do not proliferate in culture and express a limited
      repertoire of surface antigens, including CD19, CD20, CD23, CD27, CD40, and CD70.
      In this report, we demonstrate that freshly isolated B cells from a subset of CLL
      cases constitutively express CD40 ligand (CD40L, CD154), a member of the tumor
      necrosis factor family which is normally expressed by activated CD4(+) T cells
      and mediates T-cell-dependent B-cell proliferation and antibody production. The
      degree of CD40L expression varied considerably among the CLL cases examined.
      CD40L was detected in purified CLL B cells by immunofluorescence flow cytometry,
      by RT-PCR, and by immunoprecipitation. To demonstrate that CD40L in the CLL B
      cells is functional, we used irradiated CLL cells to stimulate IgG production by
      target, nonmalignant B cells in coculture. The CLL B cells induced IgG production
      by normal B cells to a similar degree as did purified T cells in a process which
      was partially inhibited by monoclonal antibody to CD40L. This is one of the first
      reports of CD40L expression in a B-cell tumor. The data suggest that CD40L in the
      tumor cells may be a factor in the generation of pathologic antibodies by normal
      B cells in some patients with CLL.

PMID- 9531578
TI  - Tissue factor-dependent vascular endothelial growth factor production by human
      fibroblasts in response to activated factor VII.
AB  - The transmembrane protein tissue factor (TF) is the cell surface receptor for
      coagulation factor VII (FVII) and activated factor VII (FVIIa). Recently, TF has
      been identified as a regulator of angiogenesis, tumor growth, and metastasis.
      This study was designed to link the binding of FVII(a) to its receptor, TF, with
      the subsequent triggering of angiogenesis through vascular endothelial growth
      factor (VEGF) production by human lung fibroblasts. We report that incubation of
      fibroblasts, which express constitutive surface TF, with FVII(a) induces VEGF
      synthesis. FVII(a)-induced VEGF secretion, assessed by a specific enzyme-linked
      immunosorbent assay, was time- and concentration-dependent. VEGF secretion was
      maximal after 24 hours of incubation of the cells with 100 nmol/L FVII(a) and
      represented a threefold induction of the basal VEGF level. Reverse transcriptase
      polymerase chain reaction analysis of VEGF detected three mRNA species of 180,
      312, and 384 bp corresponding, respectively, to VEGF121, VEGF165, and VEGF189. A
      2.5- to 3.5-fold increase was observed for the 180- and 312-bp transcripts at 12
      and 24 hours, respectively. FVII(a)-dependent VEGF production was inhibited by a
      pool of antibodies against TF, pointing to the involvement of this receptor. On
      specific active-site inhibition with dansyl-glutamyl-glycinyl-arginyl
      chloromethyl ketone, FVIIa lost 70% of its capacity to elicit VEGF production.
      Consistent with this, the native form (zymogen) of FVII only had a 1.8-fold
      stimulating effect. Protein tyrosine kinase and protein kinase C are involved in
      signal transduction leading to VEGF production, as shown by the inhibitory
      effects of genistein and GF 109203X. The results of this study indicate that TF
      is essential for VIIa-induced VEGF production by human fibroblasts and that its
      role is mainly linked to the proteolytic activity of the TF-VIIa complex.

PMID- 9531579
TI  - Long-term results from MOPPEBVCAD chemotherapy with optional limited radiotherapy
      in advanced Hodgkin's disease.
AB  - The purpose was to verify the 5-year results of the MOPPEBVCAD chemotherapy
      regimen with limited radiotherapy in relation to the promising preliminary data.
      Mechlorethamine, vincristine, procarbazine, prednisone, epidoxorubicin,
      bleomycin, vinblastine, lomustine, melphalan, and vindesine were delivered
      according to a schedule derived through hybridization, intensification, and
      shortening of the corresponding alternating CAD/MOPP/ABV regimen. Radiotherapy
      was restricted to sites of bulky involvement or to areas that responded
      incompletely to chemotherapy. This multicenter, controlled, nonrandomized trial
      involved 145 eligible patients. Radiotherapy was administered to 47 patients, 46
      of whom were in complete remission after chemotherapy. Remissions were complete
      in 137 patients (94%), partial in 4 (3%), and null in the remaining 4. Tumor
      specific, overall, relapse-free, and failure-free survival at 5 years were 0.89,
      0.86, 0.82, and 0.78, respectively. Hematologic toxicity was considerable,
      whereas nonhematologic side effects were fully acceptable. Most of the
      unfavorable prognostic factors lost their clinical weight. Only age and
      lymphocyte depletion histologic type were statistically correlated with major
      follow-up endpoints; performance status and bone marrow involvement were
      subordinate to age. Seven patients developed a second cancer (including 3
      myelodysplasias). MOPPEBVCAD with selected radiotherapy is a highly effective
      regimen in advanced Hodgkin's disease. Early and late toxicity are no more severe
      than what would be expected with other alternating or hybrid regimens. A
      comparison with ABVD, which is currently considered the standard regimen for
      advanced Hodgkin's disease, is needed.

PMID- 9531580
TI  - Randomized study on hydroxyurea alone versus hydroxyurea combined with low-dose
      interferon-alpha 2b for chronic myeloid leukemia. The Benelux CML Study Group.
AB  - Interferon-alpha (IFN-alpha) is considered the standard therapy for chronic
      myeloid leukemia (CML) patients not suitable for allogeneic stem cell
      transplantation. From 1987 through 1992, 195 patients in the Benelux with recent
      untreated CML were randomized between low-dose IFN-alpha2b (3 MIU, 5 days/wk) or
      hydroxyurea alone (control group). The white blood cell count had to be kept less
      than 10 x 10(9)/L in both arms; to this end, the IFN group received additional
      hydroxyurea, if necessary. The complete hematologic responses at 6 months in the
      IFN group were 62%, versus 38% in the control group. In the IFN group, a complete
      hematologic response at 6 months predicted a better survival (P = .001), but such
      a tendency was also seen in the control group (P = .07). Cytogenetic responses in
      the IFN group yielded 9% complete responders, 7% partial responders (<35% Ph+),
      and 24% minor responders (36% to 95% Ph+). The quality of cytogenetic response
      within the first 24 months was highly predictive for survival (P = .002). Twenty
      four patients discontinued IFN-alpha because of side effects, but they did this
      at a long median interval of 17.6 months; the remaining patients did not require
      dose adaptations. Although the hematologic and cytogenetic responses in the IFN
      group were higher than in the control group, the duration of chronic phase from
      randomization was not statistically different with 53 and 44 months in the IFN
      and control group, respectively. Also, no advantage for survival calculated from
      diagnosis was seen for the IFN group (median, 64 months) compared with the
      control group (median, 68 months).

PMID- 9531581
TI  - A placebo-controlled study of recombinant human granulocyte-macrophage colony
      stimulating factor administered during and after induction treatment for de novo
      acute myelogenous leukemia in elderly patients. Groupe Ouest Est Leucemies Aigues
      Myeloblastiques (GOELAM).
AB  - The complete remission (CR) rate after intensive chemotherapy for acute
      myelogenous leukemia (AML) remains low in elderly patients, mainly because of a
      higher infectious mortality rate related to neutropenia and an increased
      incidence of adverse prognostic factors. Granulocyte-macrophage colony
      stimulating factor (GM-CSF) has been shown to potentially recruit leukemic blasts
      into cell cycle and improve cytotoxic effects when given during chemotherapy, and
      to shorten the duration of neutropenia when administered after chemotherapy. Two
      hundred forty patients aged 55 to 75 years who had newly diagnosed AML were
      randomly assigned to receive placebo or Escherichia coli-derived GM-CSF (5
      micrograms/kg/d by 6-hour intravenous infusion) starting during induction
      chemotherapy on day 1 and continued through and after chemotherapy until recovery
      of neutrophils, or evidence of regrowth of leukemia, or up to day 28. Induction
      chemotherapy consisted of idarubicin (8 mg/m2/d on days 1 to 5) and cytarabine
      (100 mg/m2/d on days 1 to 7). The study drug was not administered subsequent to
      the induction course. Patients who achieved a CR received continuous maintenance
      therapy for 1 year with four quarterly reinduction courses; in the 55- to 64-year
      age subgroup, patients were randomly assigned to receive or not a consolidation
      course before maintenance therapy. The CR rate was similar in the GM-CSF and
      placebo groups (63% and 60.5%, respectively; P = .79). The mortality, rate of
      resistant disease, and rate of regrowth of leukemia were also similar in both
      groups. The time to neutrophil recovery was shorter in patients who received GM
      CSF (24 v 29 days; P = .0001), but the incidence and characteristics of
      infectious events were not different. The 2-year disease-free survival (DFS) rate
      was significantly improved in the GM-CSF group (48% v 21% in the placebo group; P
      = .003). This effect was highly significant in the cohort of patients aged 55 to
      64, but only marginal in patients >/=65 years of age. There was a trend toward a
      longer overall survival (OS) in the GM-CSF group (P = .082). In summary, the
      administration of GM-CSF, concomitantly with chemotherapy and thereafter during
      induction course in AML, shortened the time to neutrophil recovery, but did not
      improve the CR rate in patients aged 55 to 75. Nonetheless, DFS and OS were
      significantly prolonged in patients aged 55 to 64 treated with GM-CSF. These
      results are promising and further evaluation of myeloid growth factors in AML is
      warranted.

PMID- 9531582
TI  - Indolent systemic mast cell disease in adults: immunophenotypic characterization
      of bone marrow mast cells and its diagnostic implications.
AB  - The aim of the present study was to explore the diagnostic value of the
      immunophenotypic analysis of bone marrow mast cells (BMMC) in indolent systemic
      mast cell disease (SMCD) patients. For that purpose, a total of 10 SMCD patients
      and 19 healthy controls were analyzed. Our results show that BMMC from SMCD are
      different from normal BMMC with regard to both their light scatter and
      immunophenotypic characteristics. Accordingly, forward light scatter (FSC), side
      (90 degrees) light scatter (SSC), and baseline autofluorescence levels were
      higher in BMMC from indolent SMCD patients than they were in control subjects.
      From the immunophenotypic point of view, the most striking findings were the
      constant expression of CD2 (P = .0001), CD25 (P = .0001), and CD35 (P = .06)
      molecules by BMMC from SMCD patients, markers that were absent from all normal
      controls. In contrast, CD71, absent in BMMC from indolent SMCD, was positive in
      BMMC from normal subjects. Although, slight differences between BMMC from SMCD
      patients and normal controls were found in several other markers, they did not
      reach statistical significance. In conclusion, our results show that simultaneous
      assessment of FSC/SSC and reactivity for the CD117, CD2, CD25, CD33, and CD35
      forms the basis for the immunophenotypic characterization of BMMC from SMCD in
      adults and should be integrated with clinical and morphologic studies for the
      diagnosis of the disease.

PMID- 9531583
TI  - Bone marrow failure in the Fanconi anemia group C mouse model after DNA damage.
AB  - Fanconi anemia (FA) is a pleiotropic inherited disease that causes bone marrow
      failure in children. However, the specific involvement of FA genes in
      hematopoiesis and their relation to bone marrow (BM) failure is still unclear.
      The increased sensitivity of FA cells to DNA cross-linking agents such as
      mitomycin C (MMC) and diepoxybutane (DEB), including the induction of chromosomal
      aberrations and delay in the G2 phase of the cell cycle, have suggested a role
      for the FA genes in DNA repair, cell cycle regulation, and apoptosis. We
      previously reported the cloning of the FA group C gene (FAC) and the generation
      of a Fac mouse model. Surprisingly, the Fac -/- mice did not show any of the
      hematologic defects found in FA patients. To better understand the relationship
      of FA gene functions to BM failure, we have analyzed the in vivo effect of an FA
      specific DNA damaging agent in Fac -/- mice. The mice were found to be highly
      sensitive to DNA cross-linking agents; acute exposure to MMC produced a marked BM
      hypoplasia and degeneration of proliferative tissues and caused death within a
      few days of treatment. However, sequential, nonlethal doses of MMC caused a
      progressive decrease in all peripheral blood parameters of Fac -/- mice. This
      treatment targeted specifically the BM compartment, with no effect on other
      proliferative tissues. The progressive pancytopenia resulted from a reduction in
      the number of early and committed hematopoietic progenitors. These results
      indicate that the FA genes are involved in the physiologic response of
      hematopoietic progenitor cells to DNA damage.

PMID- 9531584
TI  - Cytokine production and function in c-mpl-deficient mice: no physiologic role for
      interleukin-3 in residual megakaryocyte and platelet production.
AB  - Mice lacking thrombopoietin (TPO), or its receptor c-Mpl, display defective
      megakaryocyte and platelet development and deficiencies in progenitor cells of
      multiple hematopoietic lineages. The contribution of alternative cytokines to
      thrombopoiesis in the absence of TPO signalling was examined in mpl-/- mice.
      Analysis of serum and organ-conditioned media showed no evidence of a
      compensatory overproduction of megakaryocytopoietic cytokines. However,
      consistent with a potential role in vivo, when injected into mpl-/- mice,
      interleukin-6 (IL-6) and leukemia inhibitory factor (LIF) retained the capacity
      to elevate megakaryocytes and their progenitors in hematopoietic tissues and
      increase circulating platelet numbers. However, double mutant mice bred to carry
      genetic defects both in c-Mpl and IL-3 or the alpha chain of the IL-3 receptor,
      displayed no greater deficiencies in megakaryocytes or platelets than mpl
      deficient animals, suggesting absence of a physiologic role for IL-3 in the
      residual megakaryocytopoiesis and platelet production in these mice.

PMID- 9531585
TI  - The SH2-containing inositol polyphosphate 5-phosphatase, ship, is expressed
      during hematopoiesis and spermatogenesis.
AB  - Ship is a recently identified SH2-containing inositol polyphosphate 5-phosphatase
      that has been implicated as an important signaling molecule in cell-culture
      systems. To understand the physiologic function of Ship in vivo, we performed
      expression studies of Ship during mouse development. Results of this study
      demonstrate the expression of ship to be in late primitive-streak stage embryos
      (7.5 days postcoitus [dpc]), when hematopoiesis is thought to begin, and the
      expression is restricted to the hematopoietic lineage in mouse embryo. In adult
      mice, Ship expression continues to be in the majority of cells from hematopoietic
      origin, including granulocytes, monocytes, and lymphocytes, and is also found in
      the spermatids of the testis. Furthermore, the level of Ship expression is
      developmentally regulated during T-cell maturation. These results suggest a
      possible role for Ship in the differentiation and maintenance of the
      hematopoietic lineages and in spermatogenesis.

PMID- 9531586
TI  - Identification of a common developmental pathway for thymic natural killer cells
      and dendritic cells.
AB  - Current data support the notion that the thymus is seeded by a yet uncommitted
      progenitor cell able to generate T cells, B cells, natural killer (NK) cells, and
      dendritic cells (DCs). We assess in this report the developmental relationship of
      DCs and NK cells derived from a small subset of CD34(+) human postnatal
      thymocytes that, like the earliest precursors in the fetal thymus, display low
      CD33 surface expression. Culture of these isolated CD34(+) CD33(lo) thymic
      progenitors with a mixture of cytokines, including interleukin-7 (IL-7), IL
      1alpha, IL-6, granulocyte-macrophage colony-stimulating factor, and stem cell
      factor, results in predominant generation of DCs. However, the addition of IL-2
      to the cytokine mixture leads to the simultaneous development of DCs and NK
      cells. Both developmental pathways progress through a transient population of
      CD34(+)CD44(bright) CD5(lo/-)CD33(+) large-sized cells, distinct from small-sized
      T-lineage precursors, that contain bipotential NK/DC progenitors. These data
      provide evidence of linked pathways of NK cell and DC development from
      intrathymic precursors and suggest that NK cells and DCs branch off the T lineage
      through a common intermediate progenitor.

PMID- 9531588
TI  - High-efficiency gene transfer into ex vivo expanded human hematopoietic
      progenitors and precursor cells by adenovirus vectors.
AB  - Replication-deficient adenoviral vectors (AdVec), which infect cycling and
      noncycling cells with high efficiency, low toxicity, and ease of delivery,
      provide ideal vehicles to study the expression of regulatory genes controlling
      different stages of hematopoiesis. To examine the infection efficiency of AdVec
      in hematopoietic precursor and progenitor cells, we used a replication-deficient
      adenovector expressing the humanized form of the cDNA for green fluorescent
      protein (AdGFP), permitting assessment of infection efficiency and kinetics of
      transgene expression in viable hematopoietic cells using flow cytometry and
      fluorescence microscopy. Flow-cytometric analysis of ex vivo expanded
      hematopoietic precursor cells infected with a multiplicity of infection (MOI) of
      100 of AdGFP show that 78% of megakaryocytic (CD41a+ and CD42b+) cells, 82% of
      dendritic (CD1a+) cells, 41% of RBC precursors (glycophorin A+), and 32% of
      monocytic (CD14(+)) cells expressed GFP. Nineteen percent +/- 1% of freshly
      isolated CD34(+) cells from peripheral blood leukapheresis products infected
      under the same conditions expressed GFP. Morphologic evaluation of ex vivo
      expanded, AdGFP-infected CD34(+) cells showed normal maturation. The functional
      capacity of AdGFP-infected CD34(+) cells was analyzed by quantifying clonogeneic
      efficiency and proliferative capacity. Infection of CD34(+) progenitor cells with
      MOIs of 1 to 100 did not impair clonogeneic efficiency of CD34(+ )cells. However,
      MOI greater than 100 resulted in a significant inhibition of colony-forming unit
      granulocyte/granulocyte-macrophage (CFU-G/GM) formation. In sequential dilution
      expansion over 3 weeks (Delta assay), the cytokine-driven proliferative potential
      of CD34(+) cells was not impaired following exposure to AdGFP at MOIs of 1 to
      1,000. The GFP+ population expanded 10- to 15-fold at high MOIs (500 to 1,000),
      indicating multiple copies of the transgene in the initially infected CD34(+)
      cells, which were expressed in subsequent progenies. These data show that AdVec
      deliver transgenes with high efficiency and low toxicity to hematopoietic
      progenitor and precursor cells. Introduction of marker genes such as GFP into
      hematopoietic cells by AdVec will provide a valuable system for study of
      development, homing, and trafficking of hematopoietic precursor and progenitor
      cells in vitro and in vivo. Furthermore, these results provide insights into the
      design of gene therapy strategies for treatment of hematologic disorders by
      AdVec.

PMID- 9531587
TI  - New insights into the negative regulation of hematopoiesis by chemokine platelet
      factor 4 and related peptides.
AB  - Platelet factor 4 (PF4) has been recognized as an inhibitor of myeloid
      progenitors. However, the mechanism of action of this chemokine remains poorly
      understood. The present study was designed to determine its structure/function
      relationship. A series of peptides overlapping the C-terminal and central regions
      of PF4 were analyzed in vitro for their action on murine hematopoietic progenitor
      growth to assess the minimal sequence length required for activity. The peptides
      p17-58 and p34-58 possessed an increased hematopoietic inhibitory activity when
      compared with PF4, whereas the shorter peptides p47-58 and p47-70 were equivalent
      to the native molecule and the peptide p58-70 was inactive. The PF4 functional
      motif DLQ located in 54-56 was required for the activity of these peptides. The
      peptide p34-58 impaired to a similar extent the growth of colony-forming unit
      megakaryocyte (CFU-MK) as well as burst-forming unit-erythroid (BFU-E) and colony
      forming unit-granulocyte-macrophage (CFU-GM), whereas PF4 was more active on CFU
      MK. In the experiments using purified murine CD34(+) marrow cells, statistically
      significant inhibition induced by p34-58 was shown at concentrations of 2.2
      nmol/L or greater for progenitors of the three lineages, whereas that induced by
      PF4 was seen at 130 nmol/L for CFU-MK and 650 nmol/L for CFU-GM and BFU-E,
      indicating that the p34-58 acts directly on hematopoietic progenitors and its
      activity is approximately 60- to 300-fold higher than PF4. The p34-58, unlike
      PF4, lacked affinity for heparin and its inhibitory activity could not be
      abrogated by the addition of heparin. In addition, an antibody recognizing p34-58
      neutralized the activity of p34-58 but not whole PF4 molecule. These results
      demonstrate that PF4 contains a functional domain in its central region, which is
      independent of the heparin binding properties, and provide evidence for a model
      of heparin-dependent and independent pathways of PF4 in inhibiting hematopoiesis.

PMID- 9531589
TI  - Elevation of the serum Fas ligand in patients with hemophagocytic syndrome and
      Diamond-Blackfan anemia.
AB  - Fas ligand (FasL) is a membrane protein that is expressed in activated T cells
      and natural killer cells. FasL binds to Fas on target cells and induces
      apoptosis. There exists a soluble form of FasL (sFasL), and sFasL also induces
      apoptosis of Fas-bearing cells. The serum sFasL concentrations were reported to
      be elevated in patients with large granular lymphocytic leukemia and natural
      killer cell lymphoma. In this study, we have measured serum sFasL concentrations
      in other hematological disorders, including severe aplastic anemia (SAA),
      hemophagocytic lymphohistiocytosis (HLH), and Diamond-Blackfan anemia (DBA). The
      serum sFasL concentration of age-matched healthy controls was 0.16 +/- 0.11 ng/mL
      (mean +/- SD, n = 22). The serum sFasL levels in the patients with HLH and DBA
      were 3.75 +/- 3.82 (n = 19; P < .0001, HLH v control) and 2.76 +/- 2.43 ng/mL (n
      = 6; P = .012, DBA v control), respectively. Serum interferon-gamma concentration
      was elevated in the patients with HLH (1.61 +/- 2.62 ng/mL) but not in those with
      DBA (below the detectable level). These results suggest that the Fas-FasL system
      plays a role, at least in part, in the pathophysiology of HLH and DBA.

PMID- 9531590
TI  - CD148 is a membrane protein tyrosine phosphatase present in all hematopoietic
      lineages and is involved in signal transduction on lymphocytes.
AB  - Evidence is presented showing that a protein tyrosine phosphatase different from
      CD45 is present on the membrane of human hematopoietic cells. The molecule
      recognized by the monoclonal antibody 143-41, which has been classified as CD148
      in the VI International Workshop on Leukocyte Differentiation Antigens, was
      immunopurified and sequenced. The sequence obtained from N-terminus as well as
      from two different CNBr-digested peptides showed a close identity with a
      previously described tyrosine phosphatase named HPTP-eta/DEP-1. CD148 is present
      on all hematopoietic lineages, being expressed with higher intensity on
      granulocytes than on monocytes and lymphocytes. Interestingly, whereas it is
      clearly present on peripheral blood lymphocytes, it is poorly expressed on
      different lymphoid cell lines of T and B origin. When this protein tyrosine
      phosphatase was cocrosslinked with CD3, an inhibition of the normally observed
      calcium mobilization was observed. This inhibition correlates with a decrease in
      phospholipase C-gamma (PLC-gamma) phosphorylation and is similar to the one
      observed with CD45. In addition, it is shown that the crosslinking of the CD148
      alone is also able to induce an increase in [Ca2+]i. This increase is abolished
      in the presence of genistein and by cocrosslinking with CD45. These data,
      together with the induction of tyrosine phosphorylation on several substrates,
      including PLC-gamma, after CD148 crosslinking, suggest the involvement of a
      tyrosine kinase-based signaling pathway in this process. In conclusion, the data
      presented show that CD148 corresponds to a previously described protein tyrosine
      phosphatase HPTP-eta/DEP-1 and that this molecule is involved in signal
      transduction in lymphocytes.

PMID- 9531591
TI  - Recurrent arterial thrombosis linked to autoimmune antibodies enhancing von
      Willebrand factor binding to platelets and inducing Fc gamma RII receptor
      mediated platelet activation.
AB  - A patient with a history of recurrent late fetal loss associated with multiple
      placental infarcts and cerebrovascular ischemia at the age of 36, followed a year
      later by a myocardial infarction, was referred for further investigation.
      Coronary angiography was normal. Antinuclear factor, lupus anticoagulant,
      anticardiolipin antibodies, and other thrombophilia parameters were negative, but
      there was moderate hyperthyroidism with positive thyroid peroxidase antibodies.
      Platelet numbers and von Willebrand factor (vWF) were normal. Her platelets
      showed spontaneous aggregation that disappeared with aspirin intake. However,
      aggregation still was induced by low levels of ristocetin (0.3 to 0.5 mg/mL). The
      low-dose ristocetin aggregation in patient platelet-rich plasma (PRP) was
      completely blocked by neutralizing antiglycoprotein Ib (GPIb) and anti-vWF
      antibodies. The monoclonal anti-Fc gamma RII receptor antibody IV.3 inhibited
      partly, which suggests that PRP aggregation by low-dose ristocetin was elicited
      by vWF-immunoglobulin (Ig) complexes. Upon addition to washed human platelets,
      with vWF (10 micrograms/mL), purified patient Igs dose-dependently enhanced
      ristocetin (0.15 mg/mL)-induced aggregation between 0 and 500 micrograms/mL, an
      effect that disappeared again above 1 mg/mL. Aggregation was dependent on the vWF
      concentration and was blocked by IV.3 or neutralizing anti-GPIb or anti-vWF
      antibodies. The spontaneous aggregation of normal platelets resuspended in
      patient plasma could be inhibited totally by IV.3 and partially by neutralizing
      anti-GPIb or anti-vWF antibodies. Perfusion with normal anticoagulated blood,
      enriched with 10% of control or patient plasma, over surfaces coated with vWF
      showed increased platelet adhesion and activation in the presence of patient
      antibodies. Treatment of the patient with the antithyroid drug thiamazol and
      temporary corticosteroids, aspirin, and ticlopidine did not correct the platelet
      hypersensitivity to ristocetin. These observations suggest that some
      autoantibodies to vWF may both enhance vWF binding to platelets and cause
      platelet activation through binding to the Fc gamma RII receptor, and thereby may
      be responsible for a new form of antibody-mediated thrombosis.

PMID- 9531592
TI  - Platelet-derived factor Va/Va Leiden cofactor activities are sustained on the
      surface of activated platelets despite the presence of activated protein C.
AB  - We investigated the role of the thrombin-activated platelet in modulating the
      rate and extent of activated protein C (APC)-catalyzed inactivation of platelet
      derived factor Va and factor VaLeiden. Platelet-derived factor Va and factor
      VaLeiden were inactivated by APC at near identical rates; however, complete
      inactivation of the cofactors was never achieved. Greater residual cofactor
      activity remained when using thrombin-activated platelets compared with that
      observed with synthetic phospholipid vesicles and platelet-derived
      microparticles, suggesting that thrombin-activated platelets protect the
      cofactors from APC-catalyzed inactivation. This apparent protection was not due
      to (1) an insufficient number of membrane binding sites for APC or factor Va; (2)
      the destruction of these sites; or (3) the presence of a platelet-associated APC
      inhibitor. Results from a plasma-based clotting assay (with or without APC) with
      platelets or PCPS vesicles added to induce clot formation indicated that, even in
      the presence of high concentrations of APC, platelets offered protection of the
      cofactor by delaying cleavage at Arg506. This resulted in incomplete proteolysis
      of the heavy chain, suggesting that platelets can also protect plasma-derived
      factor Va from APC-catalyzed inactivation. However, additional experiments
      indicated that the plasma-derived cofactor, bound to thrombin-activated
      platelets, was completely inactivated by APC, suggesting that the plasma and
      platelet-derived cofactor pools represent different substrates for APC.
      Collectively, these results indicate that platelets sustain procoagulant events
      by providing a membrane surface that delays cofactor inactivation and by
      releasing a cofactor molecule that displays an APC resistant phenotype. Thus, at
      sites of arterial injury, the factor VLeiden mutation may not as readily predict
      arterial thrombosis, because the normal and variant platelet-derived cofactors
      are equally resistant to APC at the activated platelet surface.

PMID- 9531593
TI  - Molecular mechanisms of type II factor XIII deficiency: novel Gly562-Arg mutation
      and C-terminal truncation of the A subunit cause factor XIII deficiency as
      characterized in a mammalian expression system.
AB  - To explore the biological and clinical implications of the structure/function
      relationships in factor XIII, mutations in two patients with type II deficiency
      were identified and characterized in a mammalian expression system. Nucleotide
      sequence analysis of the A subunit gene showed that case no. 1 had a deletion of
      4 bp (AATT) in exon XI and that, in case no. 2, Gly562 (GGG) had been replaced by
      Arg(AGG). The deletion in case no. 1 leads to a premature termination at codon
      464. Restriction digestion of amplified DNAs confirmed that both cases were
      homozygous for their respective mutations. Reverse transcription-polymerase chain
      reaction analysis demonstrated that the level of mRNA was greatly reduced in case
      no. 1, whereas the level of mutant mRNA expressed in case no. 2 was normal.
      Molecular modeling calculated that Arg562 changed the conformation of the A
      subunit, suggesting misfolding and/or destabilization of the molecule. To
      determine how these mutations impaired synthesis of the A subunit, recombinant A
      subunits bearing the mutations were expressed in mammalian cells. Pulse-chase
      experiments showed that the mutants were synthesized normally but disappeared
      rapidly, whereas the wild-type remained. These results indicate that both mutant
      proteins with an altered conformation become prone to rapid degradation,
      resulting in factor XIII deficiency in these patients.

PMID- 9531594
TI  - Acquired deficiency of von Willebrand factor-cleaving protease in a patient with
      thrombotic thrombocytopenic purpura.
AB  - Plasma of patients with thrombotic thrombocytopenic purpura (TTP) has been shown
      to contain unusually large von Willebrand factor (vWF) multimers that may cause
      platelet agglutination in vivo. Fresh frozen plasma infusions and plasma exchange
      represent the most efficient therapy of acute TTP. A specific protease
      responsible for cleavage of vWF multimers has been recently isolated from normal
      human plasma and was found to be deficient in four patients with chronic
      relapsing TTP. We examined the activity of the vWF-cleaving protease in plasma
      samples collected over a period of 400 days from a further patient with recurrent
      episodes of TTP who was treated by plasma exchange, plasma infusion, vincristine,
      corticosteroid therapy, and splenectomy. Complete deficiency of the vWF-cleaving
      protease was established during the first episode of TTP. The ensuing
      normalization of the platelet count was associated with the appearance of the
      protease activity. Three months after remission from the initial TTP event, the
      vWF-cleaving protease again disappeared and the platelet count gradually
      decreased. Relapses of severe thrombocytopenia occurred 7 and 11 months after the
      first acute episode of TTP. Deficient protease activity was associated with the
      presence in the patient plasma of an inhibitor that was found to be an IgG.
      Plasma exchange/infusion was followed by a temporary increase in the antibody
      titer, whereas treatment with vincristine led to a recovery of the platelet count
      without affecting the inhibitor concentration. Splenectomy and corticosteroid
      treatment resulted in disappearance of the autoantibody and normalization of the
      protease activity and of the platelet count. Our data suggest that the
      thrombocytopenia in this patient with TTP was associated with a lack of the vWF
      cleaving protease activity depleted by an autoimmune mechanism. This case,
      together with our previously reported patients, leads us to conclude that
      acquired as well as constitutional deficiency of the vWF-cleaving protease may
      predispose to TTP.

PMID- 9531595
TI  - Inhibition of eosinophil rolling and recruitment in P-selectin- and intracellular
      adhesion molecule-1-deficient mice.
AB  - To determine the relative in vivo importance of endothelial expressed adhesion
      molecules to eosinophil rolling, adhesion, and transmigration, we have induced
      eosinophilic peritonitis using ragweed allergen in P-selectin-deficient,
      intracellular adhesion molecule-1 (ICAM-1)-deficient and control wild-type mice.
      Circulating leukocytes visualized by intravital microscopy exhibited reduced
      rolling and firm adhesion in P-selectin-deficient mice and reduced firm adhesion
      in ICAM-1-deficient mice. Eosinophils exhibited reduced rolling and firm adhesion
      to endothelium in P-selectin-deficient mice. Eosinophil recruitment in P-selectin
      deficient mice ( approximately 75% inhibition of eosinophil recruitment) and ICAM
      1-deficient mice ( approximately 67% inhibition of eosinophil recruitment) was
      significantly reduced compared with wild-type mice. Eosinophil recruitment was
      not completely inhibited in P-selectin/ICAM-1 double-mutant mice (eosinophil
      recruitment inhibited approximately 62%). However, pretreatment of P
      selectin/ICAM-1-deficient mice with an anti-vascular cell adhesion molecule
      (VCAM) antibody induced near complete inhibition of eosinophil recruitment.
      Overall, these studies show that eosinophil rolling and firm adhesion is
      significantly reduced in P-selectin-deficient mice and that P-selectin, ICAM-1,
      and VCAM are important to eosinophil peritoneal recruitment after ragweed
      challenge.

PMID- 9531596
TI  - Retinoic acid selectively inhibits lipopolysaccharide induction of tissue factor
      gene expression in human monocytes.
AB  - Expression of tissue factor (TF) by activated monocytes in several diseases leads
      to disseminated intravascular coagulation. Lipopolysaccharide (LPS)-induced
      monocyte TF expression is downregulated by the nuclear hormone all-trans retinoic
      acid (ATRA). In this study, we examined the mechanism by which ATRA inhibits
      monocyte TF expression. We show that ATRA selectively inhibited LPS induction of
      TF expression in human monocytes and monocytic THP-1 cells without affecting LPS
      induction of tumor necrosis factor-alpha (TNF-alpha) and interleukin-8 (IL-8).
      Inhibition of TF expression occurred at the level of transcription as determined
      by nuclear run-on. ATRA did not significantly alter the binding or functional
      activity of the transcription factors c-Fos/c-Jun and c-Rel/p65, which are
      required for LPS induction of the TF promoter in monocytic cells. In contrast to
      the ATRA inhibition of the endogenous TF gene, LPS induction of the cloned TF
      promoter was not inhibited by ATRA in transiently transfected THP-1 cells. Our
      results demonstrate that ATRA selectively inhibited LPS-induced TF gene
      transcription in human monocytic cells by a mechanism that does not involve
      repression of AP-1- or NF-kappaB-mediated transcription.

PMID- 9531597
TI  - Single-cell analysis of the t(14;18)(q32;q21) chromosomal translocation in
      Hodgkin's disease demonstrates the absence of this translocation in neoplastic
      Hodgkin and Reed-Sternberg cells.
AB  - Using the polymerase chain reaction (PCR) technique and total DNA extracts of
      Hodgkin's disease (HD)-involved lymph nodes, the t(14;18)(q32;q21) translocation
      was detected in 37 of 115 (32.2%) cases studied. No correlation was found between
      the presence of this translocation and bcl-2 protein expression in Hodgkin and
      Reed-Sternberg (HRS) cells detected by immunohistochemistry in 58 of 96 (60.4%)
      cases. To identify the cells carrying the t(14;18) translocation, single-cell DNA
      from HRS cells isolated by micromanipulation from frozen tissue sections of lymph
      nodes was investigated by PCR amplification. Eleven cases showing a positive band
      of the same size in at least two of five PCR experiments performed on the same
      total DNA extract were selected for single-cell PCR. We postulated that this
      repeated successful amplification could be indicative of the presence of the
      t(14;18) translocation in the neoplastic HRS cells. Single cells from frozen
      tumor sections of the t(14;18)-positive OCI LY8 cell line grafted into nude mice
      served as a positive control. The bcl-2/JH rearrangement, involved in this
      translocation, could be amplified from single-cell DNA of the latter tumor,
      whereas, in all of the HD cases, HRS cells were found to be negative. We conclude
      that the t(14;18) translocation is not localized in HRS cells, but in
      nonmalignant B bystander lymphocytes, admixed with these neoplastic cells.

PMID- 9531598
TI  - Tumor B cells from non-Hodgkin's lymphoma are resistant to CD95 (Fas/Apo-1)
      mediated apoptosis.
AB  - Apoptosis mediated by the CD95 (Fas/Apo-1) molecule plays a crucial role in the
      regulation of the B-cell immune response. In this study, we examined the function
      of the CD95 antigen in B-cell-derived non-Hodgkin's lymphoma (NHL), a malignant
      disease of mature B cells. Membrane CD95 molecules were found to be
      constitutively expressed in a large number of NHL, including mantle cell (MCL, n
      = 10), lymphocytic (LCL, n = 10), follicular (FL, n = 11), and diffuse large cell
      lymphoma (DLCL, n = 9) with, however, different levels of intensity. Indeed, the
      levels of CD95 were low in MCL and LCL as compared with FL and DLCL. However,
      regardless of the intensity of expression, CD95 triggering with anti-CD95
      monoclonal antibody (MoAb) did not induce apoptosis of lymphoma B cells, while
      these cells underwent apoptosis after irradiation or staurosporine treatment.
      Further experiments were then performed to address whether apoptosis could be
      restored by B-cell activation via CD40 cross-linking. We showed that CD40
      engagement in the presence of interleukin (IL)-4 was more effective than CD40
      engagement alone in upregulating the CD95 antigen and induced CD95-mediated cell
      death in nontumoral B cells. Concerning malignant B cells, CD40 ligation in the
      presence of IL-4 strongly increased CD95 expression, but did not markedly
      increase CD95-induced apoptosis. Furthermore, using cytotoxic T cells, we showed
      that CD95L was also ineffective in inducing apoptosis in lymphoma B cells,
      whereas these cells were killed by the perforin pathway. Our findings suggest
      that the CD95-mediated cell death pathway is altered in malignant cells from the
      NHL we tested. This could be a mechanism allowing lymphoma B cells to escape from
      immune regulation.

PMID- 9531599
TI  - A novel mutant gene involved in T-lymphocyte-specific homing into peripheral
      lymphoid organs on mouse chromosome 4.
AB  - Previously, we have shown a mutant mouse DDD/1 with T-cell-specific homing defect
      that is regulated by an autosomal recessive gene, plt (paucity of lymph node T
      cells), and seems to be caused by lymph node (LN) stromal cells. In the present
      study, immunohistochemical analysis showed unusual distribution of T cells in LN,
      Peyer's patches (PP), and spleen from plt/plt, probably due to the failure of T
      cells to migrate from blood into the T-cell zone in LN or PP, or into the spleen
      white pulp across high endothelial venule or marginal zone, respectively, based
      on the experiments in which labelled T cells were injected intravenously and
      detected in the tissues. Analysis of surface L-selectin and CD44 suggested that T
      cells with memory phenotype, probably from afferent lymphatics, recruit into
      plt/plt LN. Linkage mapping by simple-sequence length polymorphism of genomic DNA
      from 190 backcross progenies produced by intercrossing with MSM/Ms, linked plt
      most closely with D4Mit237, and localized at 24.7 cM from cetromere on chromosome
      4. We discuss the possibility that a wild-type gene on plt locus encodes a
      chemokine inducing T-cell-specific homing into peripheral lymphoid tissues.

PMID- 9531600
TI  - Effects of guanine nucleotide depletion on cell cycle progression in human T
      lymphocytes.
AB  - Depletion of guanine nucleotide pools after inhibition of inosine monophosphate
      dehydrogenase (IMPDH) potently inhibits DNA synthesis by arresting cells in G1
      and has been shown to induce the differentiation of cultured myeloid and
      erythroid cell lines, as well as chronic granulocytic leukemic cells after blast
      transformation. Inhibitors of IMPDH are also highly effective as
      immunosuppressive agents. The mechanism underlying these pleiotropic effects of
      depletion of guanine nucleotides is unknown. We have examined the effects of
      mycophenolic acid (MPA), a potent IMPDH inhibitor, on the cell cycle progression
      of activated normal human T lymphocytes. MPA treatment resulted in the inhibition
      of pRb phosphorylation and cell entry into S phase. The expression of cyclin D3,
      a major component of the cyclin-dependent kinase (CDK) activity required for pRb
      phosphorylation, was completely abrogated by MPA treatment of T cells activated
      by interleukin-2 (IL-2) and leucoagglutinin (PHA-L), whereas the expression of
      cyclin D2, CDK6, and CDK4 was more mildly attenuated. The direct kinase activity
      of a complex immunoprecipitated with anti-CDK6 antibody was also inhibited. In
      addition, MPA prevented the IL-2-induced elimination of p27(Kip1), a CDK
      inhibitor, and resulted in the retention of high levels of p27(Kip1) in IL-2/PHA
      L-treated T cells bound to CDK2. These results indicate that inhibition of the de
      novo synthesis of guanine nucleotides blocks the transition of normal peripheral
      blood T lymphocytes from G0 to S phase in early- to mid-G1 and that this cell
      cycle arrest results from inhibition of the induction of cyclin D/CDK6 kinase and
      the elimination of p27(Kip1) inhibitory activity.

PMID- 9531601
TI  - Macrophage inflammatory protein-1beta induces migration and activation of human
      thymocytes.
AB  - The CC chemokine macrophage inflammatory protein 1beta (MIP-1beta), has been
      shown to be a chemoattractant preferentially activating CD4(+) CD45RA+ T
      lymphocytes. Further analysis of chemokine action on lymphocytic cells has shown
      the potent migration-promoting capacity of MIP-1beta on human thymocytes. The
      responding cells were the CD4(+) and CD8(+) single-positive (SP), as well as the
      CD4(+) CD8(+) double-positive (DP) populations, with little if any migratory
      activity on the double-negative (DN) population. The activation of thymocytes by
      MIP-1beta appeared to be a direct, receptor-mediated event as evidenced by the
      rapid mobilization of intracellular calcium, increase in proteins phosphorylated
      on tyrosine, and activation of the mitogen-activated protein kinase (MAPK)
      pathway. Radioligand binding analyses showed specific and displaceable binding of
      MIP-1beta to thymocytes with a Kd of approximately 1 nmol/L, a profile that was
      comparable with MIP-1beta binding to CCR-5-transfected NIH 3T3 cells. In
      addition, CCR-5 mRNA was detected in total thymocyte populations indicating that
      activation of thymocytes by MIP-1beta may occur through binding to CCR-5. Further
      dissection of the subpopulations showed that only the DP and CD8(+) SP
      populations expressed CCR-5 and expression data on these two populations was
      confirmed using anti-CCR-5 monoclonal antibody. These data may be suggestive of a
      role for MIP-1beta in human thymocyte activation, and show a potential route for
      HIV infectivity in the developing immune system.

PMID- 9531602
TI  - Hematopoietic remodeling in interferon-gamma-deficient mice infected with
      mycobacteria.
AB  - Control of intracellular bacterial infections requires interferon-gamma (IFN
      gamma) both for establishing a Th1 T-cell response and for activating macrophages
      to kill the bacteria. Exposure of mice deficient in IFN-gamma to mycobacterial
      infection produces an immune response characterized by a Th2 T-cell phenotype,
      florid bacterial growth, and death. We report here that IFN-gamma-deficient mice
      infected with mycobacteria also undergo a dramatic remodeling of the
      hematopoietic system. Myeloid cell proliferation proceeds unchecked throughout
      the course of mycobacterial infection, resulting in a transition to
      extramedullary hematopoiesis. The splenic architecture of infected IFN-gamma
      deficient mice is completely effaced by expansion of macrophages, granulocytes,
      and extramedullary hematopoietic tissue. These features coincide with
      splenomegaly, an increase in splenic myeloid colony-forming activity, and marked
      granulocytosis in the peripheral blood. Systemic levels of cytokines are
      elevated, particularly interleukin-6 (IL-6) and granulocyte colony-stimulating
      factor (G-CSF). These results suggest that in addition to its central role in
      cellular immunity, IFN-gamma may be a key cytokine in coordinate regulation of
      immune effector cells and myelopoiesis. This model should be valuable for
      deciphering the cross-talk between the immune response and hematopoiesis during
      bacterial infection and for improving our understanding of the mechanisms that
      control chronic infections.

PMID- 9531603
TI  - Epstein-Barr virus (EBV)-specific cytotoxic T lymphocytes for the treatment of
      patients with EBV-positive relapsed Hodgkin's disease.
AB  - Adoptive transfer of Epstein-Barr virus (EBV)-specific cytotoxic T lymphocytes
      (CTLs) is effective prophylaxis and treatment of EBV-positive immunoblastic
      lymphoma in immunocompromised patients. In 50% of patients with Hodgkin's
      disease, the tumor cells are EBV antigen-positive and may therefore also be
      suitable targets for treatment with virus-specific CTLs. However, Hodgkin's
      disease may produce several inhibitory effects on immune induction and effector
      function in vivo, which may preclude the generation or effector function of CTLs
      reactive against EBV viral proteins, including those expressed by the tumor
      cells. We have investigated whether EBV-specific CTLs could be generated ex vivo
      from 13 patients with Hodgkin's disease: nine with active relapsed disease and
      four who were in clinical remission after a first or subsequent relapse. CTL
      lines were successfully generated from nine of 13 patients (five active disease,
      four remission). Although these lines had an abnormal pattern of expansion
      comparable to EBV-specific CTLs generated from normal donors, their phenotype was
      normal except for reduced expression of the zeta chain of the T-cell receptor
      (TCR). Their cytotoxicity was also compared to EBV-specific lines generated from
      normal donors and included activity against LMP2a, one of the three weakly
      immunogenic viral antigens expressed by Hodgkin's tumor cells. To assess the
      activity of the CTLs in vivo, they were gene-marked and infused into three
      patients with multiply relapsed disease. The CTLs persisted for more than 13
      weeks postinfusion and retained their potent antiviral effects in vivo, thereby
      enhancing the patient immune response to EBV. This approach may therefore have
      value in the treatment of EBV-positive Hodgkin's disease.

PMID- 9531604
TI  - Abnormal myelocytic cell development in interleukin-2 (IL-2)-deficient mice:
      evidence for the involvement of IL-2 in myelopoiesis.
AB  - Mice lacking interleukin-2 (IL-2) developed a severe hematopoietic disorder
      characterized by the abnormal development of myeloid cells and neutropenia.
      Analysis of the bone marrow of IL-2-deficient (IL-2(-/-)) mice showed that the
      number of mature polymorphonuclear cells was decreased by 65% to 75%, and
      granulocyte/macrophage precursor cells were reduced by 50%. Bone marrow cells
      from IL-2(-/-) mice were unable to sustain myelopoiesis in lethally irradiated
      mice and in long-term bone marrow cultures (LTBMC). The addition of exogenous IL
      2 to LTBMC of IL-2(-/-) cells partially restored hematopoietic progenitor
      activity. In the bone marrow of wild-type mice, immature (Mac-1(lo)) myeloid
      cells, including myeloblasts and promyelocytes, constitutively expressed the beta
      chain of the IL-2R, and the number of Mac-1(lo)IL-2Rbeta+ cells was increased by
      twofold to threefold in IL-2(-/-) mice. During culture in the presence of IL-2
      and the absence of stromal cells, Mac-1(lo)IL-2Rbeta+ immature myeloid cells
      proliferated and gave rise to mature granulocytes and macrophages. Collectively,
      these observations indicate that defective myelopoiesis in IL-2(-/-) mice is at
      least in part a consequence of their direct dependency on IL-2, and by regulating
      the growth of immature myeloid cells, IL-2 plays an important role in the
      homeostatic regulation of myelocytic cell generation.

PMID- 9531605
TI  - Evidence that amyloidogenic light chains undergo antigen-driven selection.
AB  - AL amyloidosis is characterized by fibrillar tissue deposits (amyloid) composed
      of monoclonal light chains secreted by small numbers of indolent bone marrow
      plasma cells whose ontogenesis is unknown. To address this issue and to provide
      insights into the processes that accompanied pathogenic light chain formation, we
      isolated the complete variable (V) regions of 14 light (VL) and 3 heavy (VH)
      chains secreted by amyloid clones at diagnosis (10 Bence Jones and 4 with
      complete Igs, 9 lambda and 5 kappa) by using an inverse polymerase chain reaction
      based approach free of primer-induced biases. Amyloid V regions were found to be
      highly mutated compared with the closest germline genes in the databases or those
      isolated from the patients' DNA, and mutations were not associated with
      intraclonal diversification. Apparently high usage of the lambdaIII family
      germline gene V lambdaIII.1 was observed (4 of 9 lambda light chains). Analysis
      of the nature and distribution of somatic mutations in amyloid V regions showed
      that there was statistical evidence of antigen selection in 8 of 14 clones (7 in
      VL and 1 in VH). These results indicate that a substantial proportion of the
      amyloid clones developed from B cells selected for improved antigen binding
      properties and that pathogenic light chains show evidence of this selection.

PMID- 9531607
TI  - Wilms' tumor (WT1) gene mutations occur mainly in acute myeloid leukemia and may
      confer drug resistance.
AB  - In a previous study of acute leukemia, we have shown that WT1 gene mutations
      occur in both myeloid and biphenotypic subtypes, where they are associated with
      refractoriness to standard induction chemotherapy. We have now extended this
      study to a total of 67 cases (34 acute myeloid leukemia [AML], 23 acute
      lymphoblastic leukemia [ALL], 10 acute undifferentiated leukemia
      [AUL]/biphenotypic) and find that WT1 mutations occur in 14% of AML and 20% of
      biphenotypic leukemia, but are rare in ALL (one case). In contrast to the
      findings in Wilms' tumor, where mutations in the WT1 gene usually behave
      according to Knudson's two hit model for tumor suppressor genes, seven of eight
      leukemia-associated WT1 mutations are heterozygous, implying a dominant or
      dominant-negative mode of action in hematopoietic cells. In AML, the presence of
      a WT1 mutation is associated with failure to achieve complete remission and a
      lower survival rate. These data (1) confirm that WT1 mutations underlie a similar
      proportion of cases of AML to that seen in Wilms' tumors and (2) show for the
      first time that WT1 mutations can contribute to leukemogenesis of lymphoid as
      well as myeloid origin, suggesting that its normal role in hematopoiesis lies at
      a very early progenitor stage. The relationship of WT1 mutation to
      chemoresistance merits further investigation.

PMID- 9531606
TI  - The clinical significance of molecular response in indolent follicular lymphomas.
AB  - Most patients with follicular lymphoma (FL) achieve a complete response (CR)
      after treatment, but eventually most of them, particularly those with stage IV,
      relapse due to minimal residual disease (MRD). The t(14;18) gives rise to a
      rearrangement of the bcl-2 oncogene that constitutes an excellent target for
      detection of MRD by polymerase chain reaction (PCR). One hundred ninety-four
      previously untreated patients with indolent FL and detectable bcl-2 rearrangement
      were studied. The PCR assay was used to detect bcl-2-rearranged cells in blood
      and marrow before and after treatment. Molecular response rate was 37%, 53%, 56%,
      and 66% at 3 to 5, 6 to 8, 9 to 14, and 15 to 18 months from the start of
      therapy, respectively. Although molecular response was higher among clinical CRs,
      one third of partial responders at 3 to 5 months also achieved a molecular
      response. Patients who achieved a molecular response during the first year of
      treatment had a significantly longer failure-free survival (FFS) than those who
      did not (4-year FFS: 76% v 38%, respectively; P < .001). Similar results were
      also observed in the subset of patients in clinical CR 1 year after treatment. By
      multivariate analysis, beta2-microglobulin (beta2-M; P < .01), and molecular
      response (P < .001) were the most important variables associated with outcome.
      When we combined beta2-M and molecular response, three prognostic groups emerged:
      (1) low beta2-M and molecular responders, (2) low beta2-M and nonresponders or
      high beta2-M and responders, and (3) high beta2-M and nonresponders. The 4-year
      FFS of these 3 groups were 86%, 65%, and 23%, respectively. Finally, patients who
      achieved molecular response and sustained it had better FFS than those who either
      reverted back to PCR-positive or who never achieved molecular response. Serial
      PCR analysis to determine the molecular response in FL correlates well with
      outcome especially when combined with pretreatment beta2-M.

PMID- 9531609
TI  - p16(INK4a) gene inactivation by deletions, mutations, and hypermethylation is
      associated with transformed and aggressive variants of non-Hodgkin's lymphomas.
AB  - The molecular mechanisms underlying the pathogenesis of aggressive lymphomas and
      the histological transformation of indolent variants are not well known. To
      determine the role of p16(INK4a) gene alterations in the pathogenesis of non
      Hodgkin's lymphomas (NHLs) and the histological progression of indolent variants,
      we have analyzed the expression, deletions, and mutations of this gene in a
      series of 112 NHLs. Hypermethylation of the gene was also examined in a subset of
      tumors with lack of protein expression but without mutations or deletions of the
      gene. p16(INK4a) gene alterations were detected in 3 out of 64 (5%) indolent
      lymphomas but in 16 out of 48 (33%) primary or transformed aggressive variants.
      In the low-grade tumors, p16(INK4a) alterations were detected in 1 (4%) chronic
      lymphocytic leukemia (hemizygous missense mutation), 1 (6%) follicular lymphoma
      (homozygous deletion), and 1 (5%) typical mantle cell lymphoma (homozygous
      deletion). The two later cases followed an aggressive clinical evolution. In the
      aggressive tumors, p16(INK4a) gene alterations were observed in 2 (29%) Richter's
      syndromes (2 homozygous deletions), 3 (33%) transformed follicular lymphomas (1
      homozygous deletion and 2 nonsense mutations), 3 (43%) blastoid mantle cell
      lymphomas (2 homozygous and 1 hemizygous deletions), 5 (28%) de novo large-cell
      lymphomas (1 homozygous deletion and 4 hypermethylations), 2 lymphoblastic
      lymphomas (2 homozygous deletions), and 1 of 2 anaplastic large cell lymphomas
      (hypermethylation). Protein expression was lost in all tumors with p16(INK4a)
      alterations except in the typical chronic lymphocytic leukemia (CLL) with
      hemizygous point mutation. Sequential samples of the indolent and transformed
      phase of three cases showed the presence of p16(INK4a) deletions in the Richter's
      syndrome but not in the CLL component of two cases, whereas in a follicular
      lymphoma the deletion was present in both the follicular tumor and in the diffuse
      large-cell lymphoma. In conclusion, these findings indicate that p16(INK4a) gene
      alterations are a relatively infrequent phenomenon in NHLs. However, deletions,
      mutations, and hypermethylation of the gene with loss of protein expression are
      associated with aggressive tumors and they may also participate in the
      histological progression of indolent lymphomas.

PMID- 9531608
TI  - Wilms' tumor gene (WT1) competes with differentiation-inducing signal in
      hematopoietic progenitor cells.
AB  - The WT1 gene is a tumor-suppressor gene that was isolated as a gene responsible
      for Wilms' tumor, a childhood kidney neoplasm. We have previously reported that
      the WT1 gene is strongly expressed in leukemia cells with an increase in its
      expression levels at relapse and an inverse correlation between its expression
      levels and prognosis, thus making it a novel tumor marker for leukemic blast
      cells. Furthermore, WT1 antisense oligomers have been found to inhibit the growth
      of leukemic cells. These results strongly suggested the involvement of the WT1
      gene in human leukemogenesis. The present study was performed to prove our
      hypothesis that the WT1 gene plays a key role in leukemogenesis and performs an
      oncogenic function in hematopoietic progenitor cells, rather than a tumor
      suppressor gene function. 32D cl3, an interleukin-3-dependent myeloid progenitor
      cell line, differentiates into mature neutrophils in response to granulocyte
      colony-stimulating factor (G-CSF). However, when transfected wild-type WT1 gene
      was constitutively expressed in 32D cl3, the cells stopped differentiating and
      continued to proliferate in response to G-CSF. As for signal transduction
      mediated by G-CSF receptor (G-CSFR), Stat3alpha was constitutively activated in
      wild-type WT1-infected 32D cl3 in response to G-CSF, whereas, in WT1-uninfected
      32D cl3, activation of Stat3alpha was only transient. However, most interesting
      was the fact that G-CSF stimulation resulted in constitutive activation of
      Stat3beta only in wild-type WT1-infected 32D cl3, but not in WT1-uninfected 32D
      cl3. Thus, WT1 expression constitutively activated both Stat3alpha and Stat3beta.
      A transient activation of Stat1 was detected in both wild-type WT1-infected and
      uninfected 32D cl3 after G-CSF stimulation, but no difference in its activation
      was found. No activation of MAP kinase was detected in both wild-type WT1
      infected and uninfected 32D cl3 after G-CSF stimulation. These results
      demonstrated that WT1 expression competed with the differentiation-inducing
      signal mediated by G-CSFR and constitutively activated Stat3, resulting in the
      blocking of differentiation and subsequent proliferation. Therefore, the data
      presented here support our hypothesis that the WT1 gene plays an essential role
      in leukemogenesis and performs an oncogenic function in hematopoietic progenitor
      cells and represent the first demonstration of an important role of the WT1 gene
      in signal transduction in hematopoietic progenitor cells.

PMID- 9531610
TI  - Methylation of the p15(INK4b) gene in myelodysplastic syndromes is frequent and
      acquired during disease progression.
AB  - p15(INK4b) gene is an inhibitor of cyclin-dependent kinase (CDK) 4 and CDK6 whose
      expression is induced by transforming growth factor (TGF)beta. Recent reports
      suggest frequent methylation of the p15(INK4b) gene promoter in leukemias, and it
      has been proposed that this methylation could be necessary for leukemic cells to
      escape TGF beta regulation. We investigated the methylation status of p15(INK4b)
      gene in 53 myelodysplastic syndromes (MDS) cases, including nine that had
      progressed to acute myeloid leukemia (AML), using a recently described sensitive
      method where polymerase chain reaction (PCR) is preceded by bisulfite
      modification of DNA (methylation specific PCR). p15(INK4b) methylation was
      observed in 20 of 53 (38%) of the cases. Twenty of the 24 patients with greater
      than 10% bone marrow blasts had p15(INK4b) methylation (including all nine
      patients who had progressed to AML) as compared with none of MDS patients with
      <10% bone marrow blasts. No correlation between karyotypic abnormalities and
      methylation status was found. Patients with p15(INK4b) methylation had a worse
      prognosis, but the prognostic significance of p15(INK4b) methylation was no more
      found by multivariate analysis, due to its strong correlation to the percentage
      of marrow blasts. In 10 MDS cases, sequential DNA samples were available. In five
      of them, methylation of the p15(INK4b) gene was detected at leukemic
      transformation, but not at diagnosis. Our results showed that methylation of the
      p15(INK4b) gene in MDS is correlated with blastic bone marrow involvement and
      increases with disease evolution toward AML. It suggests that proliferation of
      leukemic cells might require an escape of regulation of the G1 phase of the cell
      cycle, and possibly of TGF beta inhibitory effect.

PMID- 9531611
TI  - Hematopoietic malignancies demonstrate loss-of-function mutations of BAX.
AB  - The BCL-2 gene family regulates the susceptibility to apoptotic cell death in
      many cell types during embryonic development and normal tissue homeostasis.
      Deregulated expression of anti-apoptotic BCL-2 can be a primary aberration that
      promotes malignancy and also confers resistance to chemotherapeutic agents.
      Recently, studies of Bax-deficient mice have indicated that the pro-apoptotic BAX
      molecule can function as a tumor suppressor. Consequently, we examined human
      hematopoietic malignancies and found that approximately 21% of lines possessed
      mutations in BAX, perhaps most commonly in the acute lymphoblastic leukemia
      subset. Approximately half were nucleotide insertions or deletions within a
      deoxyguanosine (G8) tract, resulting in a proximal frame shift and loss of
      immunodetectable BAX protein. Other BAX mutants bore single amino acid
      substitutions within BH1 or BH3 domains, demonstrated altered patterns of protein
      dimerization, and had lost death-promoting activity. Thus, mutations in the pro
      apoptotic molecule BAX that confer resistance to apoptosis are also found in
      malignancies.

PMID- 9531612
TI  - Role of p53 in hematopoietic recovery after cytotoxic treatment.
AB  - Prompt reconstitution of hematopoiesis after cytoreductive therapy is essential
      for patient recovery and may have a positive impact on long-term prognosis. We
      examined the role of the p53 tumor suppressor gene in hematopoietic recovery in
      vivo after treatment with the cytotoxic drug 5-fluorouracil (5-FU). We used p53
      knock-out (p53-/-) and wild-type (p53+/+) mice injected with 5-FU as the
      experimental model. Analysis of the repopulation ability and clonogenic activity
      of hematopoietic stem cells (HSCs) and their lineage-committed descendants showed
      a greater number of HSCs responsible for reconstitution of lethally irradiated
      recipients in p53-/- bone marrow cells (BMCs) recovering after 5-FU treatment
      than in the corresponding p53+/+ BMCs. In post-5-FU recovering BMCs, the
      percentage of HSC-enriched Lin- Sca-1(+) c-Kit+ cells was about threefold higher
      in p53-/- than in p53+/+ cells. Although the percentage of the most primitive
      HSCs (Lin- Sca-1(+) c-Kit+ CD34(low/-)) did not depend on p53, the percentage of
      multipotential HSCs and committed progenitors (Lin- Sca-1(+) c-Kit+ CD34(high/+))
      was almost fourfold higher in post-5-FU recovering p53-/- BMCs than in their
      p53+/+ counterparts. The pool of HSCs from 5-FU-treated p53-/- BMCs was exhausted
      more slowly than that from the p53+/+ population as shown in vivo using pre
      spleen colony-forming unit (CFU-S) assay and in vitro using long-term culture
      initiating cells (LTC-ICs) and methylcellulose replating assays. Clonogenic
      activity of various lineage-specific descendants was significantly higher in post
      5-FU regenerating p53-/- BMCs than in p53+/+ BMCs, probably because of their
      increased sensitivity to growth factors. Despite all these changes and the
      dramatic difference in sensitivity of p53-/- and p53+/+ BMCs to 5-FU-induced
      apoptosis, lineage commitment and differentiation of hematopoietic progenitors
      appeared to be independent of p53 status. These studies suggest that suppression
      of p53 function facilitates hematopoietic reconstitution after cytoreductive
      therapy by: (1) delaying the exhaustion of the most primitive HSC pool, (2)
      stimulating the production of multipotential HSCs, (3) increasing the sensitivity
      of hematopoietic cells to growth factors, and (4) decreasing the sensitivity to
      apoptosis.

PMID- 9531613
TI  - Characterization of nonrandom chromosomal gains and losses in multiple myeloma by
      comparative genomic hybridization.
AB  - Clonal chromosomal changes in multiple myeloma (MM) and related disorders are not
      well defined, mainly due to the low in vivo and in vitro mitotic index of plasma
      cells. This difficulty can be overcome by using comparative genomic hybridization
      (CGH), a DNA-based technique that gives information about chromosomal copy number
      changes in tumors. We have performed CGH on 25 cases of MM, 4 cases of monoclonal
      gammopathy of uncertain significance, and 1 case of Waldenstrom's
      macroglobulinemia. G-banding analysis of the same group of patients demonstrated
      clonal chromosomal changes in only 13 (43%), whereas by CGH, the number of cases
      with clonal chromosomal gains and losses increased to 21 (70%). The most common
      recurrent changes detected by CGH were gain of chromosome 19 or 19p and complete
      or partial deletions of chromosome 13. +19, an anomaly that has so far not been
      detected as primary or recurrent change by G-banding analysis of these tumors,
      was noted in 2 cases as a unique change. Other recurrent changes included gains
      of 9q, 11q, 12q, 15q, 17q, and 22q and losses of 6q and 16q. We have been able to
      narrow the commonly deleted regions on 6q and 13q to bands 6q21 and 13q14-21.
      Gain of 11q and deletion of 13q, which have previously been associated with poor
      outcome, can thus be detected by CGH, allowing the use of this technique for
      prognostic evaluation of patients, without relying on the success of conventional
      cytogenetic analysis.

PMID- 9531614
TI  - Serum level of the soluble form of the CD30 molecule identifies patients with
      Hodgkin's disease at high risk of unfavorable outcome.
AB  - Preliminary reports suggested a prognostic significance for serum levels of
      soluble CD30 (sCD30) in patients with Hodgkin's disease (HD). In this study, we
      investigated the prognostic impact of sCD30 concentration at diagnosis in
      relation to the other recognized prognostic parameters in 303 patients with HD
      observed in three different institutions between 1984 and 1996. sCD30 levels were
      correlated with stage, presence of B symptoms, and tumor burden. High sCD30
      levels entailed a higher risk of poor outcome, and the event-free survival (EFS)
      probability at 5 years for patients with sCD30 levels >/=100 and less than 100
      U/mL was 59.9% (95% confidence interval [CI], 40.6% to 65.9%) and 87.5% (95% CI,
      81.5% to 91.6%), respectively (P < .001). On the basis of the results of
      univariate analysis of 14 pretreatment characteristics, we included five
      prognostic factors (high sCD30 serum level, stage III-IV, B symptoms, low
      hemoglobin level, and age >/=50 years) into a multivariate model. High sCD30 and
      advanced stage were independently associated with an unfavorable prognosis. Their
      combined evaluation identified patients at high risk (stages III and IV and sCD30
      >/=100 U/mL: EFS, 46.9%) and low risk (stages I and II with sCD30 <100 U/mL: EFS,
      88. 7%) of treatment failure (P < .001). We conclude that the combined evaluation
      of sCD30 serum level and stage at presentation identifies patients with HD at
      high risk of an unfavorable outcome.

PMID- 9531615
TI  - Prolonged STAT1 activation related to the growth arrest of malignant lymphoma
      cells by interferon-alpha.
AB  - Multiple biologic effects of interferon-alpha (IFN-alpha), including cell growth
      inhibition and antiviral protection, are initiated by tyrosine phosphorylation of
      STAT proteins. Although this signal pathway has been intensively investigated,
      the relevance of STAT signal persistence has received scant attention. Using
      paired isogenic lymphoma cells (Daudi), which either are sensitive or resistant
      to growth inhibition by IFN-alpha, we found comparable initial tyrosine
      phosphorylation of multiple STAT proteins; however, the phosphorylation durations
      and associated DNA-binding activities diverged. Phosphorylation and DNA-binding
      capacity of STAT1 decreased after 4 to 8 hours in resistant cells, as compared
      with 24 to 32 hours in sensitive cells, whereas phosphorylation of STAT3 and
      STAT5b was briefer in both lines. Functional significance of the prolonged STAT1
      signal, therefore, was explored by experimental interruption of tyrosine
      phosphorylation, either by premature withdrawal of the IFN-alpha or deferred
      addition of pharmacologically diverse antagonists: staurosporine (protein kinase
      inhibitor), phorbol 12-myristate 13-acetate (growth promoter), or
      aurintricarboxylic acid (ligand competitor). Results indicated that an
      approximately 18-hour period of continued STAT1 phosphorylation was associated
      with growth arrest, but that antiviral protection developed earlier. These
      differences provide novel evidence of a temporal dimension to IFN-alpha signal
      specificity and show that duration of STAT1 activation may be a critical variable
      in malignant cell responsiveness to antiproliferative therapy.

PMID- 9531617
TI  - Human eosinophils express, relative to other circulating leukocytes, large
      amounts of secretory 14-kD phospholipase A2.
AB  - Human eosinophils perform several functions dependent on phospholipase A2 (PLA2)
      activity, most notably the synthesis of platelet-activating factor (PAF) and
      leukotriene C4 (LTC4). Several forms of PLA2 have been identified in mammalian
      cells. In the present study, the 14-kD, secretory form of PLA2 was detected in
      human eosinophils by immunocytochemical staining with the specific monoclonal
      antibody (MoAb) 4A1. In contrast, preparations of neutrophils, monocytes,
      lymphocytes, and basophils did not show detectable staining. With two MoAbs in a
      sandwich enzyme-linked immunosorbent assay (ELISA), large amounts of sPLA2 were
      detected in lysates of eosinophils, that were 20-fold to 100-fold higher than in
      the other circulating leukocytes (ie, neutrophils, basophils, monocytes, and
      lymphocytes). In addition, with a commercially available sPLA2 activity assay
      kit, we were able to show high activity of sPLA2 in human eosinophils relative to
      neutrophils. Investigations at the ultrastructural level showed that sPLA2 in
      eosinophils is mainly located in specific granules. Immunoelectron microscopy
      also visualized sPLA2 within phagosomes after addition of opsonized particles to
      the eosinophils. However, sPLA2 was not detected in the cell-free supernatants of
      activated eosinophils, in contrast to eosinophil-cationic protein (ECP), which
      colocalizes with sPLA2 in resting eosinophils. These findings warrant further
      studies into the role of sPLA2 in eosinophil function.

PMID- 9531616
TI  - A juxtacrine mechanism for neutrophil adhesion on platelets involves platelet
      activating factor and a selectin-dependent activation process.
AB  - The aim of this study was to identify the molecular mechanisms involved in
      neutrophil adhesion to immobilized platelets with particular focus on the
      possible existence of a juxtacrine system for neutrophil-platelet interactions.
      Platelets were immobilized onto collagen (type I)-coated coverslips that were
      placed in a flow chamber and neutrophils were perfused across these confluent
      monolayers at a shear stress of 1 to 4 dynes/cm2. Neutrophils rolled, and a
      significant proportion (25% to 50%) adhered to platelet monolayers. P-selectin
      was expressed in very large quantities on the surface of platelets and mediated
      all of the rolling, whereas the beta2-integrin mediated firm adhesion. An
      activation mechanism for adhesion was necessary inasmuch as fixed neutrophils
      continued to roll on immobilized platelets, but did not adhere. Platelets
      adherent to collagen produced significant levels of platelet-activating factor
      (PAF). Accordingly, the firm adhesion of neutrophils to platelets was
      significantly inhibited by a PAF receptor antagonist (WEB 2086). Treatment of
      only the platelets with acetylhydrolase, which converts membrane-associated PAF
      to lyso-PAF, prevented 60% of the adhesion. These data suggest that PAF, on the
      surface of platelets, mediated a significant portion of the adhesive interaction.
      Addition of some selectin-binding carbohydrates (fucoidan or soluble SLEx analogs
      but not dextran sulfate) to the platelets caused rolling neutrophils to
      immediately adhere, an event that was not observed on histamine or thrombin
      treated endothelium or P-selectin transfectants. These data support the view that
      a juxtacrine activation process exists on immobilized platelets for neutrophils.
      This process can be greatly enhanced on platelets and may involve a signaling
      mechanism through P-selectin.

PMID- 9531618
TI  - Membrane phospholipid asymmetry in human thalassemia.
AB  - Phospholipid asymmetry in the red blood cell (RBC) lipid bilayer is well
      maintained during the life of the cell, with phosphatidylserine (PS) virtually
      exclusively located in the inner monolayer. Loss of phospholipid asymmetry, and
      consequently exposure of PS, is thought to play an important role in red cell
      pathology. The anemia in the human thalassemias is caused by a combination of
      ineffective erythropoiesis (intramedullary hemolysis) and a decreased survival of
      adult RBCs in the peripheral blood. This premature destruction of the thalassemic
      RBC could in part be due to a loss of phospholipid asymmetry, because cells that
      expose PS are recognized and removed by macrophages. In addition, PS exposure can
      play a role in the hypercoagulable state reported to exist in severe beta
      thalassemia intermedia. We describe PS exposure in RBCs of 56 comparably anemic
      patients with different genetic backgrounds of the alpha- or beta-thalassemia
      phenotype. The use of fluorescently labeled annexin V allowed us to determine
      loss of phospholipid asymmetry in individual cells. Our data indicate that in a
      number of thalassemic patients, subpopulations of red cells circulate that expose
      PS on their outer surface. The number of such cells can vary dramatically from
      patient to patient, from as low as that found in normal controls (less than 0.2%)
      up to 20%. Analysis by fluorescent microscopy of beta-thalassemic RBCs indicates
      that PS on the outer leaflet is distributed either over the entire membrane or
      localized in areas possibly related to regions rich in membrane-bound alpha
      globin chains. We hypothesize that these membrane sites in which iron carrying
      globin chains accumulate and cause oxidative damage, could be important in the
      loss of membrane lipid organization. In conclusion, we report the presence of PS
      exposing subpopulations of thalassemic RBC that are most likely physiologically
      important, because they could provide a surface for enhancing hemostasis as
      recently reported, and because such exposure may mediate the rapid removal of
      these RBCs from the circulation, thereby contributing to the anemia.

PMID- 9531619
TI  - Adenosine 3':5'-cyclic monophosphate (cAMP)-inducible pyrimidine 5'-nucleotidase
      and pyrimidine nucleotide metabolism of chick embryonic erythrocytes.
AB  - Terminally differentiating erythrocytes degrade most of their RNA with subsequent
      release of mononucleotides. Pyrimidine mononucleotides are preferentially cleaved
      by an erythrocyte-specific pyrimidine 5'-nucleotidase; deficiency of this enzyme
      causes hemolytic anemia in humans. Details of the regulation of its activity
      during erythroid differentiation are unknown. The present study arose from the
      observation that the immature red blood cells (RBCs) of mid-term chick embryos
      contain high concentrations of uridine 5'-triphosphate (UTP) (5 to 6 mmol/L),
      which decline rapidly from days 13 to 14 onward. We analyzed two key enzymes of
      RBC pyrimidine nucleotide metabolism: pyrimidine nucleoside phosphorylase (PNP)
      and pyrimidine 5'-nucleotidase (P-5'-N), to evaluate if changes of enzyme
      activity during embryonic development are correlated with changes of RBC UTP.
      Secondly, we tested if these enzymes are under hormonal control. The results show
      that embryonic RBCs contain only minimal activity of PNP. In contrast, P-5'-N
      increases from day 13 on, suggesting that the enzyme is a limiting factor in UTP
      degradation. Activation of beta-adrenergic and A2A-adenosine receptors causes
      transcription-dependent de novo synthesis of P-5'-N. Because beta-adrenergic and
      adenosine receptors are also found on adult erythroid cells, P-5'-N might be an
      enzyme of differentiating RBCs whose expression is in part controlled by
      adenosine 3':5'-cyclic monophosphate (cAMP).

PMID- 9531620
TI  - Adaptive response of iron absorption to anemia, increased erythropoiesis, iron
      deficiency, and iron loading in beta2-microglobulin knockout mice.
AB  - Recently, a novel gene of the major histocompatibility complex (MHC) class I
      family, HFE (HLA-H), has been found to be mutated in a large proportion of
      hereditary hemochromatosis (HH) patients. Further support for a causative role of
      HFE in this disease comes from the observation that beta2-microglobulin knockout
      (beta2m-/-) mice, that fail to express MHC class I products, develop iron
      overload. We have now used this animal model of HH to examine the capacity to
      adapt iron absorption in response to altered iron metabolism in the absence of
      beta2m-dependent molecule(s). Mucosal uptake, mucosal transfer and retention of
      iron were measured in control and beta2m-/- mice with altered iron metabolism.
      Mucosal uptake of Fe(III), but not of Fe(II), by the mutant mice was
      significantly higher when compared with B6 control mice. Mucosal transfer in the
      beta2m-/- mice was higher, independent of the iron form tested. No significant
      differences were found in iron absorption between control and beta2m-/- mice when
      anemia was induced either by repetitive bleeding or by hemolysis through
      phenylhydrazine treatment. However, iron absorption in mice made anemic by
      dietary deprivation of iron was significantly higher in the mutant mice.
      Furthermore, the beta2m-/- mice manifested an impaired capacity to downmodulate
      iron absorption when dietary or parenterally iron-loaded. The expression of the
      defect in iron absorption in the beta2m-/- mice is quantitative, with iron
      absorption being excessively high for the size of body iron stores. The higher
      iron absorption capacity in the beta2m-/- mice may involve the initial step of
      ferric mucosal uptake and the subsequent step of mucosal transfer of iron to the
      plasma.

PMID- 9531621
TI  - Genetic and immunological properties of phage-displayed human anti-Rh(D)
      antibodies: implications for Rh(D) epitope topology.
AB  - Understanding anti-Rh(D) antibodies on a molecular level would facilitate the
      genetic analysis of the human immune response to Rh(D), lead to the design of
      therapeutically useful reagents that modulate antibody binding, and provide
      relevant information regarding the structural organization of Rh(D) epitopes.
      Previously, we described a Fab/phage display-based method for producing a large
      array of anti-Rh(D) antibodies from the peripheral blood lymphocytes of a single
      alloimmunized donor. In the current study, we present a detailed analysis of 83
      randomly selected clones. Sequence analysis showed the presence of 28 unique
      gamma1 heavy chain and 41 unique light chain gene segments. These paired to
      produce 53 unique Fabs that had specificity for at least half of the major Rh(D)
      epitopes. Surprisingly, despite this diversity, only 4 closely related heavy
      chain germline genes were used (VH3-30, VH3-30.3, VH3-33, and VH3-21). Similarly,
      nearly all Vkappa light chains (15/18) were derived from one germline gene
      (DPK9). lambda light chains showed a more diverse VL gene usage, but all (23/23)
      used the identical Jlambda2 gene. Several Fabs that differed in epitope
      specificity used identical heavy chains but different light chains. In
      particular, 2 such clones differed by only 3 residues, which resulted in a change
      from epD2 to epD3 specificity. These results suggest a model in which footprints
      of anti-Rh(D) antibodies are essentially identical to one another, and Rh(D)
      epitopes, as classically defined by panels of Rh(D) variant cells, are not
      discrete entities. Furthermore, these data imply that the epitope specificity of
      an anti-Rh(D) antibody can change during the course of somatic mutation. From a
      clinical perspective, this process, which we term epitope migration, has
      significance for the design of agents that modulate antibody production and for
      the creation of mimetics that block antibody binding in the settings of
      transfusion reactions and hemolytic disease of the newborn.

PMID- 9531622
TI  - Risks of developing Epstein-Barr virus-related lymphoproliferative disorders
      after T-cell-depleted marrow transplants. CAMPATH Users.
AB  - T-cell depletion of bone marrow for allogeneic transplantation is known to
      increase the risks of Epstein-Barr virus-driven lymphoproliferative disorders
      that may result in fatal lymphoma, especially with transplants from unrelated or
      mismatched donors. Over the past 15 years, we have monitored the outcome of 2,582
      transplants using CAMPATH-1 (CD52) antibodies to deplete lymphocytes from donor
      and/or recipient to prevent graft-versus-host disease or rejection. Unlike many
      other methods of T-cell depletion, CAMPATH-1 antibodies also deplete B
      lymphocytes. The actuarial risk of lymphoproliferative disease using CAMPATH-1
      for depletion of donor lymphocytes was up to 1.3%, hardly different from reported
      figures for conventional nondepleted transplants. In contrast, the risk in a
      small group of patients transplanted from unrelated donors using E-rosette
      depletion was as high as 29%, comparable to other reports of specific T-cell
      depletion. We conclude that the additional depletion of B cells is beneficial,
      possibly because it reduces either the virus load or the virus target until the
      time when T cells begin to regenerate.

PMID- 9531623
TI  - Might essential thrombocythemia carry Ph anomaly?

PMID- 9531624
TI  - Splenectomy in Gaucher disease: new management dilemmas.

PMID- 9531625
TI  - Hepatic lesions of chronic disseminated systemic candidiasis in leukemia patients
      may become visible during neutropenia: value of serial ultrasound examinations.

PMID- 9531626
TI  - Hydrogen uptake in Nostoc sp. strain PCC 73102. Cloning and characterization of a
      hupSL homologue.
AB  - Structural genes encoding an uptake hydrogenase of Nostoc sp. strain PCC 73102
      were isolated. From partial libraries of genomic DNA, two clones (pNfo01 and
      pNfo02) were selected and sequenced, revealing the complete sequence of both a
      hupS (960 bases) and a hupL (1,593 bases) homologue in Nostoc sp. strain PCC
      73102. A comparison between the deduced amino acid sequences of HupS and HupL of
      Nostoc sp. strain PCC 73102 and Anabaena sp. strain PCC 7120 showed that the HupS
      proteins are 89% identical and the HupL proteins are 91% identical. However, the
      noncoding region between the genes in Nostoc sp. strain PCC 73102 (192 bases) is
      longer than that of Anabaena sp. strain PCC 7120 and of many other
      microorganisms. Southern hybridizations using DNA from both N2-fixing and non-N2
      fixing cells of Nostoc sp. strain PCC 73102 and different probes from within hupL
      clearly demonstrated that, in contrast to Anabaena sp. strain PCC 7120, there is
      no rearrangement within hupL of Nostoc sp. strain PCC 73102. Indeed, 6
      nucleotides out of 16 within the potential recombination site are different from
      those of Anabaena sp. strain PCC 7120. Furthermore, we have recently published
      evidence demonstrating the absence of the bidirectional/reversible hydrogenase in
      Nostoc sp. strain PCC 73102. The present knowledge, in combination with the
      unique characteristics, makes Nostoc sp. strain PCC 73102 an interesting
      candidate for the study of deletion mutants lacking the uptake-type enzyme.

PMID- 9531627
TI  - Genes coding for respiratory complexes map on all three chromosomes of the
      Paracoccus denitrificans genome.
AB  - The genome of Paracoccus denitrificans (strain Pd1222) consists of three distinct
      DNA molecules when separated by standard pulsed-field gel electrophoresis with
      apparent molecular sizes of approximately 2, 1.1, and 0.64 Mb. When the separated
      chromosomes are digested by restriction enzymes and sizes of resulting fragments
      are summed up, the three chromosomes are composed of 1.83, 1.16, and 0.67 Mb.
      Since their migration behavior relative to size standards is largely independent
      of electrophoresis conditions, at least the two smaller chromosomes most likely
      represent linear molecules. The size analysis presented here allows an
      unequivocal distinction between groups of different strains of P. denitrificans
      and of Thiosphaera pantotropha, confirming an earlier cytochrome c analysis. When
      the genome was analyzed with different probes coding for respiratory enzymes,
      essential genes were found spread over all three chromosomes without any obvious
      clustering on any of the three forms.

PMID- 9531628
TI  - High rate of aerobic nitrification and denitrification by Nitrosomonas eutropha
      grown in a fermentor with complete biomass retention in the presence of gaseous
      NO2 or NO.
AB  - A pure culture of the obligately lithoautotrophic ammonia-oxidizer Nitrosomonas
      eutropha was grown in a laboratory-scale bioreactor with complete biomass
      retention. The air supply was supplemented with nitrogen dioxide (NO2; 25 or 50
      ppm) or nitric oxide (NO; 25 or 50 ppm). Compared to cultures grown without these
      nitrogenous oxides, the addition of NO2 or NO to the culture resulted in a
      significant increase of the nitrification rate, specific activity of ammonia
      oxidation, growth rate, and maximum cell densities. In contrast, the growth yield
      slightly decreased in the presence of NO or NO2. Maximum cell densities of about
      2 x 10(10) cells ml-1 and a maximum nitrification rate of about 221 mmol NH4+ l-1
      day-1 were obtained after 3 weeks in the presence of 50 ppm NO2. Furthermore, in
      the stationary phase about 50% of the nitrite produced was aerobically
      denitrified to dinitrogen (N2) and traces of nitrous oxide (N2O). When cells were
      supplemented with NO, a high rate of aerobic denitrification occurred only during
      the first days of the exponential growth phase.

PMID- 9531629
TI  - Methanobrevibacter filiformis sp. nov., A filamentous methanogen from termite
      hindguts.
AB  - A morphologically distinct, filamentous methanogen was isolated from hindguts of
      the subterranean termite, Reticulitermes flavipes (Kollar) (Rhinotermitidae),
      wherein it was part of the microbiota colonizing the hindgut wall. Individual
      filaments of strain RFM-3 were 0.23-0.28 micron in diameter and usually > 50
      micron in length and aggregated into flocs that were often >/= 0.1 mm in
      diameter. Optimal growth of strain RFM-3 was obtained at pH 7.0-7.2 and 30
      degrees C with a yeast-extract-supplemented, dithiothreitol-reduced medium in
      which cells produced stoichiometric amounts of methane from H2 + CO2. The
      morphology and gram-positive staining reaction of strain RFM-3, as well as its
      resistance to cell lysis by various chemical agents and its restriction to H2 +
      CO2 as an energy source, suggested that it was a member of the
      Methanobacteriaceae. The nucleotide sequence of the SSU-rRNA-encoding gene of
      strain RFM-3 confirmed this affiliation and also supported its recognition as a
      new species of Methanobrevibacter, for which the epithet filiformis is herewith
      proposed. Although M. filiformis was one of the dominant methanogens in R.
      flavipes collected from Woods Hole (Mass., USA), cells of similar morphology were
      not consistently observed in R. flavipes collected from different geographical
      locations.

PMID- 9531630
TI  - Characterization of Aquamicrobium defluvii gen. nov. sp. nov., a thiophene-2
      carboxylate-metabolizing bacterium from activated sludge.
AB  - A gram-negative bacterium was isolated from activated sewage sludge with
      thiophene-2-carboxylate as the sole source of carbon and with nitrate as an
      electron acceptor. The isolate, strain NKK, was a motile, oxidase- and catalase
      positive, rod-like bacterium with a G+C content of 61.7 mol%. Besides nitrate,
      oxygen could serve as a terminal electron acceptor. Among many carbon sources
      tested, only a few sugars, fatty acids, and thiophene-2-carboxylate supported
      growth. Other heterocyclic compounds were not used. The sulfur atom of thiophene
      2-carboxylate was oxidized to thiosulfate when cells were grown aerobically, or
      to elemental sulfur when cells were grown anaerobically with nitrate. Nitrate was
      reduced to nitrite. Growth on thiophene-2-carboxylate was dependent on the
      addition of molybdate to the medium. Tungstate, a specific antagonist of
      molybdate, inhibited growth on thiophene-2-carboxylate at concentrations > 10(-7)
      M. Three inducible enzymes involved in the metabolism of thiophene-2-carboxylate
      were detected: an ATP-, CoA-, thiophene-2-carboxylate- and Mg2+-dependent
      thiophene-2-carboxyl-CoA ligase (AMP-forming), a molybdenum-containing thiophene
      2-carboxyl-CoA dehydrogenase, and a thiophene-2-carboxyl-CoA thioesterase. The
      sequence of the 16S rRNA gene suggested a classification of strain NKK within the
      alpha-subgroup of the Proteobacteria as a new genus and species, Aquamicrobium
      defluvii gen. nov. sp. nov. (DSM 11603), closely related to Mesorhizobium sp. and
      Phyllobacterium sp., but representing a distinct lineage equal in depth to those
      of the two mentioned genera. Aquamicrobium defluvii can be distinguished from
      both genera by a distinct spectrum of substrates, the maximal growth temperature,
      and a different salt tolerance.

PMID- 9531631
TI  - Isoleucine uptake in Corynebacterium glutamicum ATCC 13032 is directed by the
      brnQ gene product.
AB  - By complementation analysis of an isoleucine-uptake-deficient Escherichia coli
      strain, it was shown that a 1.6-kb HindIII-StuI fragment of Corynebacterium
      glutamicum ATCC 13032, located downstream of the aecD gene, encodes an isoleucine
      uptake system. Sequence analysis revealed that the complementing fragment carried
      an open reading frame, termed brnQ, that encodes a protein with sequence
      similarities to branched-chain amino acid carriers of gram-positive and gram
      negative bacteria. The brnQ gene specifies a predominantly hydrophobic protein of
      426 amino acid residues with a calculated molecular mass of 44.9 kDa. A topology
      prediction by neural network computer analysis suggests the existence of 12
      hydrophobic segments that most probably form transmembrane alpha-helices. A C.
      glutamicum mutant strain harboring a defined deletion of brnQ in the chromosome
      showed a considerably lower isoleucine uptake rate of 0.04 nmol min-1 mg (dry
      mass)-1 as compared to the wild-type strain rate of 1.2 nmol min-1 mg (dry mass)
      1. Overexpression of brnQ by means of a tac promotor resulted in an elevated
      uptake rate for isoleucine of 11.3 nmol min-1 mg (dry mass)-1. Evidently, the
      brnQ gene encodes the only transport system in C. glutamicum directing isoleucine
      uptake.

PMID- 9531632
TI  - Dehalobacter restrictus gen. nov. and sp. nov., a strictly anaerobic bacterium
      that reductively dechlorinates tetra- and trichloroethene in an anaerobic
      respiration.
AB  - The highly enriched anaerobic bacterium that couples the reductive dechlorination
      of tetrachloroethene to growth, previously referred to as PER-K23, was obtained
      in pure culture and characterized. The bacterium, which does not form spores, is
      a small, gram-negative rod with one lateral flagellum. It utilized only H2 as an
      electron donor and tetrachloroethene and trichloroethene as electron acceptors in
      an anaerobic respiration process; it could not grow fermentatively. Acetate
      served as a carbon source in a defined medium containing iron as the sole trace
      element, the two vitamins thiamine and cyanocobalamin, and the three amino acids
      arginine, histidine, and threonine. The cells contained menaquinones and b-type
      cytochromes. The G+C content of the DNA was 45.3 +/- 0.3 mol%. The cell wall
      consisted of type-A3gamma peptidoglycan with ll-diaminopimelic acid and one
      glycine as an interpeptide bridge. The cells are surrounded by an S-layer; an
      outer membrane was absent. Comparative sequence analysis of the 16S rRNA sequence
      showed that PER-K23 is related to gram-positive bacteria with a low G+C content
      of the DNA. Based on the cytological, physiological, and phylogenetic
      characterization, it is proposed to affiliate the isolate to a new genus,
      Dehalobacter, with PER-K23 as the type strain of the new species Dehalobacter
      restrictus.

PMID- 9531633
TI  - The genes lmbB1 and lmbB2 of Streptomyces lincolnensis encode enzymes involved in
      the conversion of L-tyrosine to propylproline during the biosynthesis of the
      antibiotic lincomycin A.
AB  - The genes lmbA,B1,B2 in the lincomycin A production gene cluster of Streptomyces
      lincolnensis were shown to form a common transcription unit with the promoter
      located directly upstream of lmbA. The proteins LmbB1 (mol. mass, 18 kDa) and
      LmbB2 (mol. mass 34 kDa), when over-produced together in Escherichia coli,
      brought about enzyme activities for the specific conversion of both L-tyrosine
      and L-3,4-dihydroxyphenylalanine (L-DOPA) to a yellow-colored product. The LmbB1
      protein alone catalyzed the conversion of L-DOPA, but not of L-tyrosine. The
      purified LmbB1 protein showed a Km for L-DOPA of 258.3 microM. The L-tyrosine
      converting activity could not been demonstrated in vitro. The preliminary
      interpretation of these data suggests that the protein LmbB1 is an L-DOPA
      extradiol-cleaving 2,3-dioxygenase and that the protein LmbB2, either alone or in
      accord with LmbB1, represents an L-tyrosine 3-hydroxylase. This sequence of
      putative oxidation reactions on L-tyrosine seems to represent a new pathway
      different from the ones catalyzed by mammalian L-tyrosine hydroxylases or the
      wide-spread tyrosinases. The protein LmbA seemed not to be involved in this
      process. The labile, yellow-colored product from L-DOPA could not be converted to
      a picolinic acid derivative [3-(2-carboxy-5-pyridyl)alanine] in the presence of
      ammonia. Therefore, it probably is not a derivative of a cis, cis-3
      hydroxymuconic acid semialdehyde; instead, its speculative structure represents a
      heterocyclic precursor of the propylhygric acid moiety of lincomycin A.

PMID- 9531634
TI  - Anaerobic degradation of alpha-resorcylate by Thauera aromatica strain AR-1
      proceeds via oxidation and decarboxylation to hydroxyhydroquinone.
AB  - Anaerobic degradation of alpha-resorcylate (3,5-dihydroxybenzoate) was studied
      with the denitrifying strain AR-1, which was assigned to the described species
      Thauera aromatica. alpha-Resorcylate degradation does not proceed via the benzoyl
      CoA, the resorcinol, or the phloroglucinol pathway. Instead, alpha-resorcylate is
      converted to hydroxyhydroquinone (1,2,4-trihydroxybenzene) by dehydrogenative
      oxidation and decarboxylation. Nitrate, K3[Fe(CN)6], dichlorophenol indophenol,
      and the NAD+ analogue 3-acetylpyridine adeninedinucleotide were suitable electron
      acceptors for the oxidation reaction; NAD+ did not function as an electron
      acceptor. The oxidation reaction was strongly accelerated by the additional
      presence of the redox carrier phenazine methosulfate, which could also be used as
      sole electron acceptor. Oxidation of alpha-resorcylate with molecular oxygen in
      cell suspensions or in cell-free extracts of alpha-resorcylate- and nitrate-grown
      cells was also detected although this bacterium did not grow with alpha
      resorcylate under an air atmosphere. alpha-Resorcylate degradation to
      hydroxyhydroquinone proceeded in two steps. The alpha-resorcylate-oxidizing
      enzyme activity was membrane-associated and exhibited maximal activity at pH 8.0.
      The primary oxidation product was not hydroxyhydroquinone. Rather, formation of
      hydroxyhydroquinone by decarboxylation of the unknown intermediate in addition
      required the cytoplasmic fraction and needed lower pH values since
      hydroxyhydroquinone was not stable at alkaline pH.

PMID- 9531635
TI  - Structure, organization, and expression of genes coding for envelope components
      in the archaeon Methanosarcina mazei S-6.
AB  - The antigenic mosaics of archaeal species are complex and lead to the distinction
      of different immunotypes. We began the dissection of the antigenic mosaic of the
      methanogen Methanosarcina mazei S-6 by gene cloning and sequencing. The analysis
      of the sequence, organization, and in vitro (heterologous) and in vivo expression
      of two three-gene clusters that encode proteins localized to the cell envelope
      and that are recognized by antibodies for surface structures is presented in this
      report. The amino acid sequences and compositions share characteristics with S
      layer proteins and, most notably, have repeats of conserved sequences and
      secondary structures. Expressed genes produced proteins with a tendency to
      oligomerize, and one of these proteins was susceptible to breakdown at regular
      intervals. Altogether, the data reveal a modular system (clusters of homologous
      genes, proteins of similar sequences with conserved repeats) seemingly suitable
      for assembling an enormous variety of final molecular structures by rearranging
      and combining genes, proteins, and repeats, and thus generate the observed wide
      spectrum of antigenic diversity.

PMID- 9531636
TI  - Investigation of the fumarate metabolism of the syntrophic propionate-oxidizing
      bacterium strain MPOB.
AB  - The growth of the syntrophic propionate-oxidizing bacterium strain MPOB in pure
      culture by fumarate disproportionation into carbon dioxide and succinate and by
      fumarate reduction with propionate, formate or hydrogen as electron donor was
      studied. The highest growth yield, 12.2 g dry cells/mol fumarate, was observed
      for growth by fumarate disproportionation. In the presence of hydrogen, formate
      or propionate, the growth yield was more than twice as low: 4.8, 4.6, and 5.2 g
      dry cells/mol fumarate, respectively. The location of enzymes that are involved
      in the electron transport chain during fumarate reduction in strain MPOB was
      analyzed. Fumarate reductase, succinate dehydrogenase, and ATPase were membrane
      bound, while formate dehydrogenase and hydrogenase were loosely attached to the
      periplasmic side of the membrane. The cells contained cytochrome c, cytochrome b,
      menaquinone-6 and menaquinone-7 as possible electron carriers. Fumarate reduction
      with hydrogen in membranes of strain MPOB was inhibited by 2-(heptyl)-4
      hydroxyquinoline-N-oxide (HOQNO). This inhibition, together with the activity of
      fumarate reductase with reduced 2,3-dimethyl-1,4-naphtoquinone (DMNH2) and the
      observation that cytochrome b of strain MPOB was oxidized by fumarate, suggested
      that menequinone and cytochrome b are involved in the electron transport during
      fumarate reduction in strain MPOB. The growth yields of fumarate reduction with
      hydrogen or formate as electron donor were similar to the growth yield of
      Wolinella succinogenes. Therefore, it can be assumed that strain MPOB gains the
      same amount of ATP from fumarate reduction as W. succinogenes, i. e. 0.7 mol
      ATP/mol fumarate. This value supports the hypothesis that syntrophic propionate
      oxidizing bacteria have to invest two-thirds of an ATP via reversed electron
      transport in the succinate oxidation step during the oxidation of propionate. The
      same electron transport chain that is involved in fumarate reduction may operate
      in the reversed direction to drive the energetically unfavourable oxidation of
      succinate during syntrophic propionate oxidation since (1) cytochrome b was
      reduced by succinate and (2) succinate oxidation was similarly inhibited by HOQNO
      as fumarate reduction.

PMID- 9531637
TI  - Net efflux of citrate in Penicillium simplicissimum is mediated by a transport
      protein.
AB  - Penicillium simplicissimum excreted citrate, isocitrate, and succinate when grown
      in a strongly buffered medium [1 M Mes (pH 6) or 1 M Hepes (pH 7.3)]. Growth in a
      weakly buffered medium did not lead to citrate excretion despite a similar
      intracellular citrate concentration. When nongrowing, citrate-excreting hyphae
      were aerated in a glucose solution, the following steady-state intracellular
      concentrations of organic acids were measured: succinate (25 mM); citrate,
      isocitrate, malate, and fumarate (all less than 5 mM). After 2 h of incubation,
      the extracellular concentrations of these acids were [micromol (g dry wt.)-1]:
      isocitrate [100], citrate [60], succinate [30], and malate, fumarate, and alpha
      ketoglutarate [<5]. The excretion of citrate was due neither to an unspecific
      change in the permeability of the plasma membrane nor to simple diffusion of
      undissociated citric acid. The involvement of a transport protein in citrate
      excretion was indicated because N-ethylmaleimide and sodium azide inhibited
      citrate excretion strongly despite an unchanged outward-directed citrate
      gradient. Arguments are given why efflux via a citrate uptake carrier is not
      considered probable. These results indicate that citrate is excreted by P.
      simplicissimum via a transport protein that probably specifically mediates the
      efflux of citrate.

PMID- 9531638
TI  - Regulation of poly(beta-hydroxybutyrate) synthesis in Methylobacterium
      rhodesianum MB 126 growing on methanol or fructose.
AB  - The intracellular concentration of CoA metabolites and nucleotides was determined
      in batch cultures of Methylobacterium rhodesianum grown on methanol and shifted
      to growth on fructose. The intracellular concentration of CoA decreased from a
      high value of 0.6 nmol/mg poly(beta-hydroxybutyrate)-free bacterial dry mass
      during growth on methanol to a low value of 0.03 nmol/mg poly(beta
      hydroxybutyrate)-free bacterial dry mass after a shift to fructose as a carbon
      source. The levels of NADH, NADPH, and acetyl-CoA were also lower. Under these
      conditions, acetyl-CoA was metabolized by both citrate synthase and beta
      ketothiolase, and poly(beta-hydroxybutyrate) synthesis and growth occurred
      simultaneously during growth on fructose. Moreover, the level of ATP was
      approximately 50% lower during growth on fructose, supporting the hypothesis of a
      bottleneck in the energy supply during the growth of M. rhodesianum with
      fructose.

PMID- 9531639
TI  - Phylogenetic position of an obligately chemoautotrophic, marine hydrogen
      oxidizing bacterium, Hydrogenovibrio marinus, on the basis of 16S rRNA gene
      sequences and two form I RuBisCO gene sequences.
AB  - Two form ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO) genes from the
      obligately autotrophic, marine hydrogen oxidizer Hydrogenovibrio marinus were
      sequenced. The deduced amino acid sequences of both RuBisCOs revealed that they
      are similar to those of sulfur oxidizers (Thiobacillus) and a purple sulfur
      bacterium (Chromatium vinosum). According to the 16S rRNA gene sequences, H.
      marinus is also affiliated with these microorganisms, members of Thiomicrospira
      being the closest relatives. Sequence similarities of the 16S rRNA genes and of
      the RuBisCO genes among these gamma-Proteobacteria suggest a common autotrophic
      ancestry. An ancestor of purple sulfur bacteria might be a common root of H.
      marinus and related sulfur oxidizers.

PMID- 9531640
TI  - [Gene diagnosis and genetic counselling of Rb gene mutations in retinoblastoma
      patients and their family members].
AB  - OBJECTIVE: To develop a diagnostic test for direct identification of disease
      causing mutation in the patients with retinoblastoma and correct prediction of
      carrier- status in unaffected adults and newborns in the RB kindred. METHODS:
      Southern blot hybridized by Rb cDNA and other intragenic probes were used to
      detect big deletions or rearrangements at Rb gene locus. SSCP analysis and direct
      sequencing of primer-directed enzymatic amplification to identify point mutations
      as small as a single nucleotide change. RFLPs and VNTRs within the Rb gene were
      used as genetic markers for haplotype analysis. RESULTS: The probands from 79 RB
      kindreds were identified to have Rb gene mutation, including 25 somatic mutations
      and 54 germline mutations (36 new germline mutations, 15 inherited mutations and
      3 mosaicisms). The WBC DNAs from their family members were also analyzed for
      determining origin and carrier of mutation. CONCLUSION: The direct identification
      of causing- cancer mutations by combining SSCP analysis and direct DNA sequencing
      showed many advantages than other indirect methods such as haplotype analysis. It
      can distinguish hereditary RB from nonhereditary RB and identify the unaffected
      carriers without family history and informes affected family member. This method
      is helpful in gene diagnosis and genetic counselling.

PMID- 9531641
TI  - [Expression of human ciliary neurotrophic factor gene in Escherichia coli].
AB  - OBJECTIVE: To express biologically active human ciliary neurotrophic
      factor(hCNTF) gene in Escherichia coli. METHODS: Total RNA was extracted from
      human peripheral nerves and cDNA was synthesized by superscript reverse
      transcriptase, a polymerase chain reaction(PCR) was conducted to obtain a full
      length cDNA fragment encode for hCNTF gene. After recovery from gel and
      purification, the PCR product was cloned into the pGEM-5Zf(+) vector and DNA
      sequence analysis was performed to verify hCNTF gene. The hCNTF gene was then
      placed under control of T7 promoter in the expression vector pET-11d and
      transformed into Escherichia coli strain BL21(DE3). Cultures of this transformat
      were induced by IPTG for the expression of recombinant protein. The bioactivity
      of recombinant protein was evaluated by its ability to support the survival of
      embryonic chick dorsal root ganglion neurons in culture. RESULTS: The human CNTF
      gene was cloned and biologically active hCNTF was expressed efficiently. Based on
      densitometry of stained gel,the recombinant hCNTF accounted for more than 25% of
      the total bacterial protein. CONCLUSION: The cloning and expression at high level
      of hCNTF gene in E.coli provides a basis for understanding the structure-activity
      relationship of CNTF and its potential clinical application.

PMID- 9531642
TI  - [Polymorphisms of four microsatellite markers closely linked with PKD1 in
      Chinese].
AB  - OBJECTIVE: To investigate the polymorphisms and evaluate the value in gene
      diagnosis of four microsatellites, which are the KG8 that locating in
      3'untranslated region of PKD1 and SM6, CW4 and CW2, closely linked to PKD1.
      METHODS: The DNAs of some unrelated Chinese Han people were analyzed by using
      PCR, PAGE and silver staining and the findings were compared with those reported
      on Caucasian. RESULTS: In Chinese, KG8 included 6 alleles and PIC was 0.312; in
      Caucasian,8 alleles,PIC 0.545. The number of alleles and PIC of KG8 in Chinese
      were not so many as those in Caucasian. SM6 included 24 kinds of alleles and PIC
      was 0.80 in Chinese; in Caucasian,16 alleles, PIC 0. 653. CW4 is 9 alleles in
      Chinese and PIC of SM6 were more than those in Caucasian. In Chinese CW4, 9
      alleles, PIC 0.850; in Caucasian, 9 alleles, PIC 0.782. Although the number of
      CW4 allele in the two nations was the same, PIC in Chinese was higher than that
      in Caucasian. In Chinese CW2,7 alleles, PIC 0.814; and in Caucasian, 13 alleles,
      PIC 0.809. The number of allele of CW2 in Chinese was not so many as that in
      Caucasian; however,the PIC was about the same. CONCLUSION: The results indicate
      that there are differences in the number of allele and distribution of the four
      microsatellite markers between Chinese and Caucasian. So there exists difference
      of dinucleotide repeat between two nations. In addition,SM6, CW4 and CW2 could be
      used as valuable markers in gene linkage diagnosis and personal and related
      identification in forensic medicine.

PMID- 9531643
TI  - [Molecular cytogenetic study on four human esophageal cancer cell lines].
AB  - OBJECTIVE: To investigate the possible involvement of chromosome abnormalities in
      pathogenesis of human esophageal cancer. METHODS: Four cell lines of human
      esophageal cancer (EC) established in our laboratory were analysed using
      interphase fluorescence in situ hybridization (FISH), chromosome painting
      technique and comparative genomic hybridization (CGH). RESULTS: Chromosome gain
      of 1,2,3,8,16, 17, and 20 was found in the four cell lines, and loss of
      chromosome Y in cell line EC8712, EC8733 and EC8501 was noted. Other frequent
      changes were partial deletion of 1p, translocation of 2q and amplification of 5p
      in all 4 cell lines, and amplification of 8q and 13q in EC8733 and deletion of
      17p in EC8712. CONCLUSION: The data suggest that nonrandom chromosome aberrations
      may play an important role in the pathogenesis of human esophageal cancer.

PMID- 9531644
TI  - [Detection of hemophilia A carriers by PCR analysis of hind III polymorphism in
      the factor VIII gene].
AB  - OBJECTIVE: To explore a scheme of using PCR analysis in the detection of carriers
      of Hind III polymorphism of factor VIII gene of hemophilia A. METHODS:
      Implicating intron 19 of the factor VIII gene of 6 patients with the hemophilia A
      and 207 unrelated X-chromosomes were amplified by PCR and were analysed by means
      of Amp-RFLPs of Hind III. RESULTS: The incidence of the polymorphic Hind III
      sites in the given population was found to be 0.29. The frequence of the Hind III
      heterozygotes in women calculated according to Hardy-Weinberg equation was 0.41,
      which proved to be informative enough for carrier detection and prenatal
      diagnosis of hemophilia A. 2 out of 6 families (33%)examined in this study were
      informative. CONCLUSION: The new scheme proved to be effective for hemophilia A
      carrier detection and prenatal diagnosis.

PMID- 9531645
TI  - [A study of genetic heterogeneity in Pfeiffer syndrome].
AB  - OBJECTIVE: To understand the molecular pathology of Pfeiffer syndrome. METHODS:
      DNA from peripheral blood was examined in 4 families with Pfeiffer syndrome by
      SSCP-sequence analyses and PCR-restriction enzyme digestion. RESULTS: The authors
      found the mutations of FGFR2 gene in two families, an A to G transition in the 3'
      acceptor splice site of intron 8 in a family, and Asp321 Ala substitution in exon
      9 in another family. In addition, the mutation in exon 5 of FGFR1 gene
      (Pro252Arg) was found in a family. CONCLUSION: These findings reveal the genetic
      heterogeneity of Pfeiffer syndrome and can help one understand the molecular
      mechanism of the disease.

PMID- 9531646
TI  - [Cytogenetic analysis of 600 cases with chronic myelogenous leukemia].
AB  - OBJECTIVE: This was a retrospective analysis of cytogenetic data from 600 cases
      with chronic myelogenous leukemia (CML) to investigate the features of Ph
      chromosome and its significance. METHODS: Bone marrow direct method and/or short
      term culture were used to prepare the chromosomes and karyotype analysis was
      performed with R-banding technique. RESULTS: 30 cases (5%) were Ph negative; 570
      cases (95%) were Ph positive. 535 cases (93.8%) had standard Ph translocation;34
      cases(5.9%) had variant translocation, including 13 cases (2.2%) with simple
      variant translocation, 13 cases (2.2%) with complex variant translocation and 8
      cases (1.4%) with masked Ph chromosome. 526 cases (92.2%) had 100% of Ph positive
      cells; 44 cases (7.7%) had normal karyotype in partial or all metaphases after
      treatment such as allogeneic bone marrow transplantation, interferon and pulse
      hydroxyurea therapy, but conventional chemotherapy had no effect on the
      percentage of Ph positive cells. 50.6% of Ph positive CML with blast crisis had
      extra chromosomal abnormalities, of which, the most common ones were +8(46.1%),2
      Ph(33.9%) and i(17q) (23%) in descending order. CONCLUSION: These facts indicate
      that chromosome examinations not only help diagnose and differentiate CML,but
      also help predict the blast crisis, evaluate the therapeutic effect, and make a
      cytogenetic classification for CML.

PMID- 9531647
TI  - [Distribution of three STR loci in Jingpo ethnic group in Yunnan province].
AB  - OBJECTIVE: This study was aimed at the use of old blood stains for investigating
      the distribution of three STR loci in Jingpo ethnic group. METHODS: DNA
      extraction from old blood stains (106 in number) and multiplex amplification of
      CSF1PO, TPOX and TH 01 were carried out. Using denaturing polyacrylamide gel
      electrophoresis and silver stain, the authors investigated the distribution of
      allele frequencies of CSF1PO, TPOX and TH01 loci in a Jingpo ethnic group in the
      southwestern part of Yunnan province. RESULTS: 7 alleles and 26 genotypes of
      CSF1PO locus,7 alleles and 19 genotypes of TPOX locus, and 6 alleles and 18
      genotypes of TH01 locus were observed. CONCLUSION: The satisfactory results
      demonstrate that multiplex amplification of CSF1PO, TPOX and TH01 is sensitive
      and the old stain of a drop of blood is sufficient for such amplification.

PMID- 9531648
TI  - [Polymorphism analysis of 4 loci of X-chromosome in a Chinese population of the
      Han nationality].
AB  - OBJECTIVE: To investigate the polymorphism of 4 loci of X-chromosome in the Hans.
      METHODS: Using PCR-SSLP, the authors analysed the polymorphism of DXS1068,
      DXS7132, DXS6804 and DXS6799 in the X-chromosome in 70 randomly selected female
      Hans. RESULTS: The number of alleles in the 4 loci were 5,5,5 and 6 respectively;
      there were no significant differences between the observed and estimated and
      genotype probabilities of the 4 loci; the estimates of heterozygosity of 4 loci
      were 0.6819, 0.6895, 0.7659 and 0.6483 respectively and there were no significant
      differences between the observed and estimated heterozygosity of the 4 loci.
      CONCLUSION: The distribution of alleles and genotype probabilities of 4 loci all
      observe the Hardy-Weinberg equilibrium.

PMID- 9531649
TI  - [Detection of SMN gene deletions in spinal muscular atrophy].
AB  - OBJECTIVE: Survival motor neuron gene(SMN) and neuronal apoptosis inhibitory
      protein gene (NAIP) have been identified as the candidates of progressive spinal
      muscular atrophy (SMA)-determining genes. The aims of this study were to
      investigate the absence of SMN gene exon 7 in Chinese SMA patients, to confirm
      the relationship between the deletion of the SMN and SMA further, and to
      establish methods for gene diagnosis and prenatal diagnosis of SMA. METHODS: PCR
      SSCP with silver staining method was used to detect the genomic DNA of 37 SMA
      patients and 30 normal individuals for deletions of SMN exon 7. RESULTS:
      Homozygous deletion of the SMN exon 7 was identified in 86.7%(13/15) of type I
      SMA patients and 86.4%(19/22) of type II patients. In the 88 controls (including
      parents of patients and normal individuals), homozygous absence of SMA exon 7 was
      only found in a mother of a patient. CONCLUSION: The data support that homozygous
      absence of SMN exon 7 is strongly associated with SMA. The percentage of
      homozygous deletions in this study is almost as high as that reported by other
      researchers. This method is useful, reliable and effective for gene diagnosis and
      prenatal diagnosis of SMA.

PMID- 9531650
TI  - [Sequencing analysis of human K-ras oncogene exon 1 in Chinese people].
AB  - OBJECTIVE: To investigate the mutation of human K-ras oncogene in the blood of
      patients with lung cancer. METHODS: PCR and sequencing methods were used to
      analyse the exon 1. Twelve patients'blood samples and 31 normals' blood samples
      were detected. RESULTS: In all 43 samples, the K-ras codon 11 was CCT (proline),
      and the opposite strand sequenced was AGG. It was different from the standard
      GCT(Alanine) sequenced by foreign authors. CONCLUSION: The 11th codon of the
      human K-ras oncogene in Chinese is CCT (Proline). As the K-ras codon 12 is a hot
      spot, this finding may be of importance to clinical genetic diagnosis.

PMID- 9531651
TI  - [Association between angiotensin II type I receptor gene and human essential
      hypertension].
AB  - OBJECTIVE: To determine whether the angiotensin II type I receptor gene might be
      implicated in human essential hypertension. METHODS: This was a case-control
      study on hypertension and normal blood pressure in Chinese DNA abstracted samples
      from 51 cases of essential hypertension and 74 normal controls were analysed by
      polymerase chain reaction,digestion of restriction enzyme and electrophesis.
      RESULTS: The genotype frequency of 1166A/1166C was 0. 196 (10/51) in the
      essential hypertension group, 0.081 (6/74) in the control group. The genotype
      frequency of 1166C/1166C was 0 in both groups. The gene frequency of 1166C was
      0.098 in the essential hypertension group, 0.041 in the controls. There was a
      significant increase in allelic frequency of 1166C in hypertension. CONCLUSION:
      The results indicate that the increase in allelic frequency of 1166C is a risk
      factor and hence suggest that the change in the angiotensin II type I receptor
      gene is associated with essential hypertension.

PMID- 9531652
TI  - [Fluorescence-based semi-automated gene scan with microsatellite markers by
      multiplex PCR techniques].
AB  - OBJECTIVE: To develop a high output and low cost multiplex PCR approach to
      facilitating large scale gene scan and gene typing with microsatellite markers.
      METHODS: 5-15 pairs of primers of microsatellite loci were added in one single
      tube with 5ul reaction volume, containing 10 mmol/L Tris-HCl (pH8.3), 50 mmol/L
      KCl,0. 1mg/ml gelatin, 3.0 mmol/L MgCl2, 200micromol/L dNTPs (each), 0.25U Taq
      DNA polymerase, Taq Start antibody and DNA templates. PCR thermocycles were
      carried out on Perkin Elmer Gene Amp PCR System 9600 with touch-down algorithm
      (the annealing temperature was decreased by 0.5 C in each cycle) to meet the
      different demands of different primers. RESULTS: Up to 10-15 loci were labeled by
      different fluorescents or by the same fluorescent, but their PCR amplification
      fragments did not overlap in size. Almost all target microsatellite loci were
      successfully co-amplified in a 5 microliter reaction volume,electrophoresized and
      analyzed in a single gel lane with Perkin Elmer ABI 373A DNA sequencer, and 9
      microsatellite loci were well genotyped. CONCLUSION: This high output and low
      cost genotyping protocol is applicable to gene mapping, human evolution and
      forensic analysis.

PMID- 9531653
TI  - [A FISH technique for simultaneous detection of fluorescent R-band and in situ
      hybridization signals].
AB  - OBJECTIVE: To develop a simple method for detecting DNA probes directly on R
      banded chromosomes. METHODS: After sixty-seven hours culture, human peripheral
      blood lymphocytes were synchronized for 5 to 6 hours by adding Hoechst 33258 and
      BUdR, and then arrested by standard cytogenetic procedures. The slides were
      mounted with 2 x SSC and exposed with a 20W UV light which was about 10cm above
      the slides for 20 min at 75 degrees C. The biotinylated probes, such as the
      cosmid and YAC clones on 5p specific region and pBamX7, were hybridized on to the
      slides. After washing, the slides were treated with avidin-FITC and amplified
      with additional layer of biotinylated anti-avidin and avidin-FITC, and
      counterstained with propidium iodide in an antifade solution. Fluorescent signals
      and R-bands were observed simultaneously under Olympus BX 60 fluorescence
      microscope equipped with a WIB filter. RESULTS: The chromosomal location of the
      greenish-yellow signals could be directly identified on the R-banded chromosome
      background. CONCLUSION: This method can serve as a rapid and precise system for
      chromosomal localization of DNA markers.

PMID- 9531654
TI  - [The detection and isolation of fetal nucleated erythrocytes from maternal blood
      using flow cytometry].
AB  - OBJECTIVE: To isolate fetal nucleated red blood cells (NRBCs) from maternal blood
      and to confirm its fetal origin. METHODS: Monoclonal antibody against the
      glycophorin A (GPA) was used to identify nucleated erythrocytes in the peripheral
      blood of pregnant women. Candidates fetal cells from 3 pregnancies at 16 to 24
      weeks of gestation were isolated successfully. Sorted cells were also confirmed
      using Y-special probe (PY3.4) repeated sequences (SRY) in maternal blood from
      women carrying male fetuses were detected by polymerase chain reaction (PCR).
      RESULTS: The PY3.4 position hybridization rates were 31.5%, 0 and 38%
      respectively in sorted GPA positive cells (GPA+)of 3 samples by FISH, and the
      results of GPA+ cells of the 3 cases by PCR were positive, negative and positive
      respectively, which were manifested by the gender after aborticide. CONCLUSION:
      This study demonstrates that fetal NRBCs are present in the peripheral blood of
      pregnant women and it is possible to isolate and detect them.

PMID- 9531655
TI  - Why are syphilis control programs failing?

PMID- 9531656
TI  - Two-tiered health care: the root of ethical problems in recent clinical trials.

PMID- 9531657
TI  - Prevalence, burden, and control of syphilis in Haiti's rural Artibonite region.
AB  - OBJECTIVES: A study was conducted to determine the prevalence and health
      consequences of syphilis and to evaluate existing control measures in a Haitian
      rural district of 200,000 people served by 12 community dispensaries and Hospital
      Albert Schweitzer. METHODS: Syphilis seroprevalence among consecutive women
      receiving antenatal services was assessed using rapid plasma reagin (RPR)
      screening and fluorescent treponemal antibody absorption (FTA-ABS) confirmatory
      testing. Hospital and dispensary records were used to review genital ulcer
      disease and syphilis cases seen during 1995. RESULTS: Of 811 pregnant women
      attending prenatal clinics during a 3-month period in 1996, 46 (5.7%) were RPR
      reactive. Syphilis seroreactivity was confirmed in 45 (97.8%) of 46 samples by
      FTA-ABS. Of 649 women attending dispensaries in the valley 41 (6.3%) were
      syphilis seroreactive compared with 4 (2.5%) of 162 women attending dispensaries
      in the mountains (OR = 2.66; P = 0.056). In 1995, 620 cases of genital ulcer
      disease were seen at the community dispensaries. At the central hospital, 257 new
      diagnoses of syphilis were made in 1995, including 30 cases of primary and
      secondary syphilis, 168 cases of latent disease, 17 cases of recurrent infection,
      9 cases of tertiary disease, and 33 cases of congenital syphilis. CONCLUSIONS:
      The 33 cases of congenital syphilis, a rate of 550 cases for 100,000 live births,
      clearly demonstrated a failure of local control measures. Decentralized prenatal
      screening for syphilis, same-day treatment of seroreactors, and strengthened
      partner treatment were initiated. Further studies to improve primary prevention
      of syphilis in rural populations have been started. Other strategies, including
      mass treatment of high-risk groups, should be investigated.

PMID- 9531658
TI  - Malaria surveillance in New York City: 1991-1996.
AB  - BACKGROUND: The transmission of malaria has increased in recent years in many
      countries where it was once eradicated or under control, and malaria remains a
      major cause of morbidity and mortality throughout the developing world. Imported
      cases of malaria have been increasing in New York City and throughout the United
      States during the past decade. The New York City Department of Health has
      modified its malaria surveillance program in order to improve the assessment of
      diagnosis and treatment of malaria in New York City residents and to provide
      appropriate advice to health professionals who treat these patients. OBJECTIVES:
      To describe the epidemiologic and clinical characteristics of laboratory
      confirmed cases of malaria diagnosed in New York City residents from January 1,
      1991, through December 31, 1996. METHODS: The retrospective study of case reports
      was carried out by the Malaria Surveillance Program of the Bureau of Communicable
      Diseases, New York City Department of Health, New York City, NY. It included the
      laboratory diagnosis of malaria and the species involved, and included also
      descriptive epidemiologic information of patients with malaria (age, sex,
      race/ethnicity, date and place of onset of illness, travel history, immigration
      status, previous history of malaria, history of blood transfusion, drugs used for
      treatment or prophylaxis), as well as a record of clinical complications of the
      infection (thrombocytopenia, hemolysis, anemia, cerebral malaria, renal failure,
      respiratory distress syndrome, fatal outcome). RESULTS: Malaria was diagnosed in
      988 residents of New York City during the 5-year period from January 1, 1991,
      through December 31, 1995. The largest number of cases, 254 (26%), occurred in
      1996, with the majority of these cases (76%) observed between the months of May
      and October. Sixty-four percent (627) of these cases were males. The age range of
      cases was from newborn (first day of life) to 83 years (median, 31 years). Of the
      962 cases of whom the racial/ethnic identity was known, 580 (59%) were black/non
      Hispanic and 255 (26%) were Asian/Pacific Islander. Travel outside of the United
      States was reported by 958 patients, the majority to Africa (569/958, 59%). Only
      139 patients (14%) claimed the use of malaria prophylaxis during travel.
      Plasmodium falciparum was identified in 505 (51%) and P. vivax in 356 (36%) of
      the cases. Clinical complications included hemolysis with severe anemia,
      thrombocytopenia, cerebral malaria, renal failure, and respiratory distress
      syndrome. All four fatal cases involved infections with P. falciparum, either
      alone or in combination with another plasmodia species. CONCLUSIONS: Imported
      cases of malaria occur frequently in New York City and may be associated with
      serious complications. Health care providers should consider this diagnosis in
      patients who have recently travelled or arrived from abroad, presenting with
      headache, fever, and other constitutional symptoms. There are many missed
      opportunities for the use of malaria prophylaxis, and physicians should
      familiarize themselves with current recommendations for malaria prophylaxis for
      travel to areas of the world where people are at risk for the transmission of
      malaria.

PMID- 9531659
TI  - Meningococcal meningitis among Rwandan refugees: diagnosis, management, and
      outcome in a field hospital.
AB  - OBJECTIVE: To study the diagnostic process, clinical course, and outcome of
      Rwandan refugees with meningococcal meningitis, treated in an Israeli field
      hospital in Goma, Zaire, in the summer of 1994. METHODS: Patient hospital charts
      and laboratory records were reviewed with critical evaluation of clinical
      presentation and diagnostic tests. Patients were treated as part of a disaster
      relief effort in a refugee camp experiencing several coexisting lethal epidemics.
      RESULTS: A total of 65 patients were identified as having group A meningococcal
      meningitis. Latex agglutination test for Neisseria meningitidis soluble antigen
      in the cerebrospinal fluid was found to be a superior diagnostic tool, as
      compared to Gram stain, and at least as effective as culture. The mortality rate
      was 14%; mortality was markedly affected by co-morbidity (e.g., dysentery,
      pneumonia, and malnutrition). CONCLUSIONS: The outcome of patients with
      meningococcal meningitis, treated in referral centers within a disaster area may
      be favorable, despite overwhelming coexisting epidemics, and may be comparable to
      that achieved in advanced medical facilities. Encephalopathy may be a diagnostic
      pitfall in the perspective of coexisting epidemics, requiring a high index of
      suspicion and routine lumbar puncture. The latex agglutination test is highly
      useful in achieving prompt diagnosis of meningococcal meningitis, in particular
      when sample handling for culture and microscopy is suboptimal.

PMID- 9531661
TI  - Varicella pneumonitis: clinical presentation and experience with acyclovir
      treatment in immunocompetent adults.
AB  - OBJECTIVE: Cases of varicella pneumonitis were reviewed to examine the effects of
      acyclovir therapy on outcome. METHODS: A retrospective chart review was done of
      all admissions of adults to two hospitals, between 1985 and 1995, because of
      complications of chickenpox. RESULTS: Fifteen patients were hospitalized for
      varicella pneumonitis during this period. No patient had a history of chickenpox
      as a child; all had a recent history (within 2-4 weeks prior to admission) of
      exposure to chickenpox in their family or neighborhood and developed respiratory
      symptoms 1 to 4 days after the appearance of the rash. Twelve patients (80%) had
      a history of cigarette smoking, and seven patients had a platelet count below the
      normal range. All patients were treated with intravenous acyclovir within 24
      hours of admission, and all but one survived and were discharged from the
      hospital without comorbid conditions. The one mortality was attributed to
      bacterial superinfection. CONCLUSIONS: Acyclovir treatment may be of benefit for
      varicella pneumonitis, but no controlled trial has been performed to definitively
      answer this question.

PMID- 9531660
TI  - Relationship of HLA-DQA1 alleles and humoral antibody following measles
      vaccination.
AB  - BACKGROUND: The human leukocyte antigen (HLA)-DQA1 locus is only moderately
      polymorphic compared to other HLA class II loci; however, we hypothesized that
      these polymorphisms could be important in determining the humoral antibody
      response to measles vaccine virus. METHODS: The seroprevalence of measles
      antibody was determined in 881 school children who had been immunized with MMR-II
      at age approximately 15 months. All subjects resided in a geographic area with no
      circulating measles virus. The IgG antibody levels were determined by a measles
      specific whole virus enzyme immunoassay (EIA) (BioWhittaker, Walkersville, MD).
      Subjects who were nonresponders (IgG seronegative or equivocal) (n = 46) and
      hyperresponders (upper 10th percentile of IgG levels of all subjects) (n = 64)
      were HLA-DQA1 typed using polymerase chain reaction with sequence-specific
      primers (PCR-SSP). The HLA-DQA1 allele frequencies, as well as homozygosity
      rates, were compared between the nonresponders and hyperresponders. RESULTS: The
      overall allele frequency distribution of alleles between the nonresponders and
      hyperresponders was significantly different (P = 0.05), with nonresponders having
      an excess of HLA-DQA1*05 alleles (P = 0.017) and hyperresponders having an excess
      of HLA-DQA1*01 alleles (P = 0. 016). The homozygosity rate among nonresponders
      was significantly higher than among hyperresponders (23.9% vs. 9.4%, P = 0.037).
      CONCLUSION: HLA-DQA1 alleles have important associations with the antibody
      response to measles vaccine. Specifically, the carriage of the HLA-DQA1*05
      alleles is associated with nonresponse and that of HLA-DQA1*01 alleles with
      hyperresponse. In addition, HLA-DQA1 homozygosity is significantly associated
      with poor antibody response to measles vaccine.

PMID- 9531662
TI  - Ivermectin for Sarcoptes scabiei hyperinfestation.
AB  - OBJECTIVES: Crusted (Norwegian) scabies is an unusual variant of scabies caused
      by hyperinfestation with Sarcoptes scabiei. It has high morbidity, and secondary
      bacterial skin sepsis may result in life-threatening bacteremia. An open label
      study of oral ivermectin was carried out in patients with crusted scabies
      refractory to topical therapy. METHODS: Patients with refractory crusted scabies
      were prescribed oral ivermectin, one to three doses of 200 mg/kg at 14-day
      intervals, combined with topical scabicide and keratolytic therapy. RESULTS: Of
      the 20 patients who received ivermectin, 8 had a complete initial clinical
      response, a partial response was achieved in 9, and minimal improvement occurred
      in 3. Three doses of ivermectin were curative for 8 of 10 cases, but recurrence
      of scabies from presumed reinfestation occurred in at least half of these.
      CONCLUSION: The authors conclude that ivermectin is effective for crusted
      scabies; however, multiple doses may be required to achieve a cure, and
      recurrence 6 or more weeks after completing treatment is common.

PMID- 9531664
TI  - Outbreak of Salmonella enteritidis gastroenteritis: investigation by pulsed-field
      gel electrophoresis.
AB  - OBJECTIVE: Pulsed-field gel electrophoresis (PFGE) was used to investigate an
      outbreak of gastroenteritis caused by Salmonella enteritidis. The outbreak
      occurred among university undergraduates who consumed contaminated food. METHOD:
      Molecular typing was done by analyzing DNA band patterns of isolates of S.
      enteritidis after digestion of chromosomal DNA with infrequently-cutting
      restriction endonucleases XbaI, AvrII, and SpeI and separation of DNA fragments
      using PFGE. RESULTS: Twenty-nine outbreak isolates of S. enteritidis had
      identical or highly similar PFGE patterns, whereas different PFGE patterns were
      observed among three epidemiologically unrelated isolates obtained during the
      same period. CONCLUSION: The data obtained confirm the value of PFGE in
      epidemiologic investigations of outbreaks caused by S. enteritidis.

PMID- 9531663
TI  - Molecular epidemiology of tuberculosis in Prague: analysis by restriction
      fragment length polymorphism.
AB  - OBJECTIVES: To characterize by restriction fragment length polymorphism (RFLP)
      patterns, the distribution of different Mycobacterium tuberculosis strains
      isolated consecutively from 75 tuberculosis patients who resided in Prague and
      had culture-confirmed cases during a 4-month period in 1995. METHODS: The
      insertion sequence IS6110-based RFLP analysis of M. tuberculosis isolates was
      carried out. RESULTS: There were a total of 75 patients with various forms of
      tuberculosis (54 males; 21 females). The sources of M. tuberculosis isolates were
      sputum (n = 64), pleura or lymph node drainage (n = 8), and urine (n = 3). Fifty
      three of the patients (70.7%) had isolates with unique RFLP patterns, while 22
      (29.3%) had isolates that belonged to seven clusters of related RFLP patterns.
      The seven clusters consisted of four groups of two patients, two groups of four
      patients, and one group of six patients. Most of the patients whose isolates fell
      within a clustered RFLP pattern lived in different quarters of the city and had
      no identifiable contacts with other patients whose isolates had the same pattern.
      CONCLUSIONS: The finding that isolates from most patients (70.7%) had unique
      rather than clustered RFLP patterns suggests that endogenous reactivation rather
      than exogenous transmission is the major determinant of most of the tuberculosis
      cases in Prague. The occurrence of seven distinct clusters comprising 29.3% of
      the isolates suggests that approximately one third of cases developed active
      tuberculosis from recent exogenous transmission.

PMID- 9531665
TI  - [Pharmacotherapy of degenerative joint diseases in dogs].
AB  - The pharmacological treatment of degenerative joint diseases is restricted
      essentially to the alleviation of acute symptoms of activated arthropathies.
      Suitable compounds are the non-steroidal and steroidal antiinflammatory drugs,
      which however do not allow long-term therapy due to their overall catabolic
      effects on cartilage metabolism. Since causally acting drugs are not available,
      the progressive course of the disease cannot be prevented so far. Natural
      components of the cartilage's matrix, being recommended as so-called
      chondroprotective drugs, do not fulfill the expectation of a remission of the
      degenerative process. Indeed, regarding the necessity of multiple local
      applications of these drugs, they are not superior to antiinflammatory drugs.
      Provided careful dosing and surveillance of untoward gastrointestinal effects,
      non-steroidal antiinflammatory agents still are the drugs of first choice.

PMID- 9531666
TI  - [Are glycosaminoglycans responsible for the therapeutic effect of mussel extract?
      A contribution to the current controversy].
AB  - For years the mechanism of action of mussel extract has been explained as due to
      the presence of glycosaminolgycans (GAG). In this study our aim was to determine
      the content and type of GAG in mussel extract using the revised more specific
      DMMB method. Relevant amount of classical GAG could not be detected either in
      pure mussel extract or in feed supplements containing mussel extract. On the
      basis of the results of our study and a comprehensive literature search we reach
      the conclusion that the effects induced by mussel extract can not be mediated by
      GAG.

PMID- 9531668
TI  - [Ophthalmology quiz. Intraocular tumor, most probably melanoma of the ciliary
      body].

PMID- 9531667
TI  - [Case report. Male Doberman, 11 months old. Pyodermic form of demodicosis].

PMID- 9531669
TI  - [Doppler echocardiographic assessment of left ventricular diastolic function in
      dogs].
AB  - Pulmonary venous flow velocity pattern, transmitral flow pattern, isovolumic
      relaxation time, and left ventricular fractional wall thinning were analyzed in
      72 dogs with heart disease by transthoracic Doppler and M-mode echocardiography
      and compared with other noninvasive variables of left ventricular and left atrial
      systolic performance. Abnormal diastolic blood flow was found in 49 (68%) dogs,
      predominantly flow patterns suggestive of relaxation abnormality and increased
      filling pressures. Diastolic flow abnormalities despite normal systolic
      performance were found in 23 (32%) dogs of which 14 (61%) revealed clinical signs
      of heart disease. The diagnostic sensitivity of pulmonary venous flow parameters
      for echocardiographically detectable diastolic disturbance was found to be higher
      compared with the other noninvasive parameters of diastolic heart function
      measured. Diastolic filling pattern appear to correlate closer with functional
      status in many dogs with heart disease than indices of systolic performance.

PMID- 9531670
TI  - [Treatment of mitral valve insufficiency in dogs with the ACE inhibitor
      enalapril. A clinical progress study].
AB  - The efficacy and safety of the angiotensin converting enzyme inhibitor enalapril
      in dogs with naturally acquired class III or class IV heart failure was evaluated
      in this study. Eighteen small-breed dogs with insufficiency of their mitral
      valves, but without other diseases were included in this study over a period of
      six months. When necessary due to massive pulmonary edema or high serum potassium
      concentrations, furosemide was added to the therapy with enalapril. No other
      drugs, including digitalis, were used in this study. The treatment was followed
      by anamnesis, clinical examinations, electrocardiography, radiography,
      echocardiography and laboratory diagnosis. Examinations were performed before
      treatment and after one week, after six weeks and after six months of treatment.
      72% of the dogs improved in NYHA classification until the end of the study (p <
      0.05). The incidence of seizures due to syncopes or severe respiratory distress
      decreased during this study (p < 0.01). For 28% of the dogs this treatment was
      not successful. In the electrocardiographic, radiographic and laboratory
      examinations statistically significant changes could not be recorded. The
      decrease in heart rate did not reach statistical significance. The
      echocardiographic investigation evaluated a significant decrease in fractional
      shortening and in the diastolic diameter of the left ventricular wall (p < 0.05
      respectively p < 0.01), but no significant change in the diastolic or systolic
      diameter of the interventricular septum. The average oral dose of enalapril was
      0.38 mg/kg body weight b.i.d., the average dose of furosemide was 0.37 mg/kg body
      weight b.i.d. in the first week of the study and was raised to 0.74 mg/kg body
      weight b.i.d. until the end of the study. Side effects like diarrhea, vomiting or
      reduced appetite did not increase during the course of the study. However one dog
      was excluded from the study because of repeated vomiting after six weeks of
      treatment. This study shows the beneficial clinical and hemodynamic effects and
      the security of the therapy with enalapril for dogs with heart failure due to
      mitral insufficiency.

PMID- 9531671
TI  - [Incidence of bacterial cystitis in diabetic dogs and cats at the time of
      diagnosis. Retrospective study for the period 1990-1996].
AB  - Bacterial cystitis is a problem often found among patients suffering from
      diabetes mellitus. Insulin management can be impaired by this condition.
      Diagnosis and therapy of a urinary tract infection are very important in
      regarding the possibility of bacteria ascending to the kidneys because in a great
      amount of diabetic patients the kidneys are already damaged by diabetic
      glomerular nephropathy. Compared to other patients of our clinic the frequency of
      cystitis among diabetic dogs (n = 158, cystitis diagnosed in 12.7%) and cats (n =
      71, cystitis diagnosed in 9.9%) was already considerably higher when diabetes
      mellitus was diagnosed in these animals. In this retrospective study female
      animals were far more affected than males. The diagnosis of cystitis among cats
      and dogs was most frequent when patients had already been suffering from
      polydipsia and polyuria for more than four weeks. A division among the dogs
      depending on the etiology of diabetes mellitus led to the following result:
      especially patients suffering from Cushing's disease and bitches with
      progesterone-STH-induced diabetes mellitus--particularly when endometritis or
      pyometra was found--were running the highest risk of developing urinary
      infections. The bacterium most frequently isolated in the urine samples was E.
      coli.

PMID- 9531672
TI  - [Administration of combination therapy with synthetic pgf2alpha analogs and a
      dopamine agonist for the termination of unwanted pregnancy in pregnant dogs. A
      study of six cases].
AB  - Analogous to the study of Onclin and Verstegen of 1996 the combination of a
      dopamine agonist, cabergoline, and a synthetic analogue of prostaglandin F2
      alpha, cloprostenol or dinoprost, was used to induce termination of pregnancy 25
      (+/- 2) days after the first mating. The study was done in six bitches.
      Cabergoline was administered at a dose of 5 micrograms/kg daily over a period of
      nine days and cloprostenol was injected subcutaneously at 1-2 micrograms/kg
      (dinoprost at a dose of 25 micrograms/kg) every other day. Treatment efficacy was
      100%. No side effects were observed. Pregnancy and its termination was diagnosed
      by ultrasonographic examination. The combination of cabergoline and cloprostenol
      offers a simple and safe procedure for the termination of unwanted pregnancy.

PMID- 9531673
TI  - [Imported arthropod-borne parasites and parasitic arthropods in dogs. Species
      spectrum and epidemiologic analysis of the cases diagnosed in 1995/96].
AB  - Between January 1995 and December 1996 nonendemic or only regionally occurring
      arthropodborne parasites including ehrlichiae and parasitic arthropods in Germany
      were detected in 484 dogs, whereby at least 15 species were involved. Listed in
      decreasing order, Leishmania infections occurred most frequently, followed by
      infections/infestations with Babesia canis, Ehrlichia canis, Rhipicephalus
      sanguineus, Dirofilaria immitis and Dermacentor reticulatus. The other species,
      namely Babesia gibsoni, Trypanosoma congolense, Hepatozoon canis, Ehrlichia
      platys, Dirofilaria repens, Dipetalonema reconditum, Dermacentor marginatus,
      Boophilus microplus and Cordylobia anthropophaga were demonstrated in a few or
      single dogs. Irrespective of the pathogen-species, most of the dogs had travelled
      with their owners to Mediterranean countries or to Portugal or had been imported
      from there. Infections with B. canis were diagnosed very frequently in dogs
      returning from Hungary. Of the 28 dogs with previous residence in Germany only,
      twelve and four animals were infected with B. canis and E. canis, respectively,
      and seven and five dogs were infested with R. sanguineus and D. marginatus,
      respectively.

PMID- 9531674
TI  - [Coat color in dogs. 1: Basics of coat color genesis].
AB  - Within this brief review of literature the biochemical and physiological basics
      of coat colour genetics in the domestic dog are described. Parallels to the
      wildcolour of the wolf are shown, out of which the most of the today known colour
      mutations developed. Furthermore the 10 most important of the today known coat
      color genloci are listed and some breed and nomenclature examples are also given.
      As the actual knowledge concerning the coat color inheritance is not able yet to
      explain some occurring coat colours and -combinations, an all-breed including
      nomenclature is not possible until today.

PMID- 9531675
TI  - [Cryptosporidiosis in adders (Pituiophis melanoleucus sayi)].
AB  - Infection of snakes with cryptosporidia is known to occur as hypertrophic
      gastritis associated with postprandial regurgitation. This is a report of a
      severe and fatal intestinal cryptosporidiosis in a group of snakes (Pituophis
      melanoleucus sayi) kept at a zoological garden. The clinical and pathological
      findings are described and discussed in this paper. Pathohistologically
      fibrinous, diphtheroid and necrotizing enteritides were diagnosed. Histological
      examination was completed by electron microscopy. Transmission electron
      microscopic examination revealed numerous cryptosporidia in close contact to the
      luminal surface of the intestinal epithelial cells. Different cryptosporidial
      stages developing in parasitophorous vacuoles occurred. By scanning electron
      microscopy the superficial localisation of the cryptosporidia in the damaged
      brush border of the intestinal epithelial cells was demonstrated. In addition,
      the ultrastructural examination of the small intestine of three animals revealed
      adenovirus-like particles.

PMID- 9531676
TI  - [Examination of the lower respiratory tract of Psittacines and Amazoniae
      varieties by means of reconstructed computer x ray tomography. 1: Examination of
      healthy parrots].
AB  - The number of psittacines kept as pets is rapidly increasing in Germany. The main
      cause of disease and death in these and other tropical birds are respiratory
      tract affections. Yet, a lack of consolidated, systematic research on the anatomy
      and pathology of these affections in gray parrots and amazons still widely
      persists. In a first step examinations on the anatomy of the respiratory tract of
      gray parrots and amazons were performed. By the means of computed tomography,
      morphological structures as well as volume and density measurements were
      conducted on this subject for the first time. By this, important, fundamental
      knowledge on the anatomy of the different parts of the psittacine respiratory
      tract as well as aspects of volume and density were gained. The computed
      tomography (CT) proved to be a valuable, informative and due to its non-invasive
      application, a careful method for examining patients. These aspects recommend it
      in the examination and research projects of other endangered exotic species as
      well. Due to its ability to image a longitudinal cross section as a standard
      cross section--which is not possible in humans or large animals--better
      information on the expansion of organs/structures in the longitudinal body axis
      could be obtained. A remarkable reduction of costs and performance time as well
      as the possibility of a direct comparison with conventional radiographs is also
      given. In a second step, with the use of the CT, pathological alterations in
      diseased gray parrots and amazons were then assessed based on anatomical data
      gained in the previous investigations on healthy birds. These results will be
      described later in a second part.

PMID- 9531677
TI  - [How dangerous is nutrition?].

PMID- 9531678
TI  - Uptake of foreign DNA from the environment: the gastrointestinal tract and the
      placenta as portals of entry.
AB  - Foreign DNA (deoxyribonucleic acid) is part of our environment. Considerable
      amounts of foreign DNA of very different origin are ingested daily with food. In
      a series of experiments we fed the DNA of bacteriophage M13 as test DNA to mice
      and showed that fragments of this DNA survive the passage through the
      gastrointestinal (GI) tract in small amounts (1-2%). Food-ingested M13 DNA
      reaches peripheral white blood cells, the spleen and liver via the intestinal
      epithelia and cells in the Peyer's patches of the intestinal wall. There is
      evidence to assume that food-ingested foreign DNA can become covalently linked to
      mouse-like DNA. When M13 DNA is fed to pregnant mice the test DNA can be detected
      in cells in various organs of the fetuses and of newborn animals, but never in
      all cells of the mouse fetus. It is likely that the M13 DNA is transferred by the
      transplacental route and not via the germ line. The consequences of foreign DNA
      uptake for mutagenesis and oncogenesis have not yet been investigated.

PMID- 9531679
TI  - [Functional results and long-term outcome after bilateral lung transplantation
      for pulmonary hypertension].
AB  - Pulmonary hypertension (PH) signifies elevated blood pressure in the pulmonary
      circulation either due to clearly defined causes (cardiac, pulmonary
      parenchymatous, systemic) or of idiopathic origin (primary PH, PPH). While
      conservative treatment is beneficial only for a small number of patients, lung
      transplantation represents a curative measure. The optimal form of
      transplantation [i.e. single lung (SLTX), bilateral lung (BLTX) or combined heart
      lung transplantation (HLTX)] is still under discussion. This study is a
      retrospective analysis of 16 patients with different forms of PH who underwent
      BLTX from 1992 to 1996 in Vienna. Four patients had Eisenmenger's disease due to
      atrial septum defect, 3 had chronic thromboembolic PH and 9 had PPH. BLTX with
      cardiopulmonary bypass was the standard procedure in all patients. Acute
      retransplantation had to be performed in 3 patients. Mean pulmonary arterial
      pressure was reduced from 63 +/- 11 mmHg preoperatively to 23 +/- 5 mmHg on the
      second day postoperatively (p < 0.0001), while the cardiac index concomitantly
      improved from 2.1 +/- 0.5 to 3.9 +/- 1.2 l/min/m2 (p < 0.05). Echocardiography
      proved normalisation of right ventricular wall thickness and end-diastolic
      diameter within 12 months, while tricuspid insufficiency, present in all patients
      before transplantation, resolved completely. Perioperatively 4 patients (25%)
      died due to septic complications (n = 3) or therapy refractory rejection (n = 1).
      Follow-up of the remaining patients ranged from 6 to 51 months (mean 33 +/- 17).
      One patient died at 8 months due to fungal sepsis. Eleven patients (68%) are
      currently alive. Only 2 of them show functional signs of chronic allograft
      rejection (bronchiolitis obliterans syndrome). All patients are at present in
      NYHA functional class I or II. In conclusion, BLTX results in complete recovery
      of right ventricular function and morphology and offers good functional long-term
      results. Because SLTX correlates with a high incidence of reperfusion edema, and
      HLTX is seriously limited by the scarcity of donor organs, BLTX should be the
      method of choice for treating end stage PH.

PMID- 9531681
TI  - [Publications: good or bad? Critical appraisal of scientific publications].
AB  - Doctors interested in medical research are flooded by publications in numerous
      scientific journals. Scientific manuscripts manifest, however, a wide range in
      terms of quality and conclusiveness, irrespective of their scientific context and
      the reader ought to be able to assess the value of the presented data and
      information. We have thus compiled a checklist in an attempt to provide the
      doctor with a relatively simple means of distinguishing between "good" and "bad"
      publications, even if he/she is not concerned with scientific methodology issues
      on a routine basis. Some aspects of "publication bias" are also touched upon in
      order to point out certain problems from the opposite perspective, namely that of
      the physician concerned with active scientific work.

PMID- 9531680
TI  - [Disseminated intravascular coagulation (DIG) with massive hyperfibrinolysis in
      metastatic uterine cancer. Observations on the effects on the coagulopathy of
      various treatments (a case report)].
AB  - We report on a 64-year-old patient with a recurrent endometrial carcinoma which
      was associated with disseminated intravascular coagulation (DIC) and excessive
      hyperfibrinolysis. The patient presented with severe bleeding due to
      hypofibrinogenemia. Fibrin degradation products were excessively elevated and
      there were also increased levels of activation markers of coagulation. Free
      plasmin was demonstrated in the circulation and alpha 2-antiplasmin was almost
      completely depleted. No increase in t-PA or u-PA level was demonstrated.
      Antifibrinolytic treatment led to a decrease of fibrin degradation products, but
      to an increase of activation markers of coagulation and was not associated with
      an increase of fibrinogen. Combination chemotherapy led to a rapid decrease of
      activation markers of coagulation and a sustained increase of fibrinogen. The
      beneficial effects on DIC/hyperfibrinolysis occurred despite the absence of any
      measurable effect of chemotherapy on the tumour. The patient finally died due to
      progression of the tumour, but without recurrence of the DIC/hyperfibrinolysis.

PMID- 9531682
TI  - [Toxoplasmosis screening: tu felix Austria--response].

PMID- 9531683
TI  - [Toxoplasmosis screening: tu felix Austria?].

PMID- 9531684
TI  - Quantification of hepatitis C virus RNA by RT-PCR in comparison to the branched
      DNA method.
AB  - INTRODUCTION: Quantification of hepatitis C virus (HCV) serum viremia levels is
      an important measure to predict and monitor response to interferon-alpha therapy
      as well as to predict clinical outcome. We were interested to compare the most
      widely used HCV quantification methods, quantitative RT-PCR (qRT-PCR) and the
      branched DNA (bDNA) method, with respect to sensitivity and reliability. RESULTS:
      In the present study, 101 serum samples from patients chronically infected with
      HCV were simultaneously quantified by an in-house reverse transcriptase (RT)-PCR
      assay and the branched DNA Quantiplex HCV RNA kit 1.0 and 2.0. The concentration
      of HCV RNA molecules/ml serum ranged from 1.5 x 10(4) to 1.0 x 10(8) as assessed
      by our quantitative (q)RT-PCR. Serum concentrations of HCV-genotype 1 were
      significantly higher when measured with bDNA 1.0 compared to bDNA 2.0 and qRT
      PCR, whereas measurements by qRT-PCR and bDNA 2.0 were concordant. Measurements
      of genotypes 2 and 3 by bDNA 2.0 were significantly higher than by bDNA 1.0.
      Significantly lower measurements were obtained for genotype 3 by qRT-PCR in
      comparison to bDNA 2.0. CONCLUSION: Despite subtype-specific differences, there
      is clinically sufficient agreement in measurements between qRT-PCR and bDNA of
      HCV RNA concentrations. However, with respect to the therapeutic monitoring of
      the individual patient, kits and methods should not be exchanged.

PMID- 9531685
TI  - The effect of sennosides on colonic mucosal histology and bowel preparation.
AB  - INTRODUCTION: A single high dose of sennosides is often used to optimize bowel
      preparation for diagnostic procedures. From previous studies it is suspected that
      sennosides in such a dose cause acute damage to the colonic mucosa. This study
      was designed to determine any effects of sennosides on histology of colonic
      mucosa and on bowel preparation. RESULTS: In a prospective study 171 patients
      were randomized for bowel preparation. 84 patients received 1 ml/kg (maximal 75
      ml) of a syrup containing 2.0 mg/ml sennoside A and B and 3-5 l of a lavage
      solution (Sen), 87 patients only received 3-5 l lavage solution (NSen). All
      patients completed a questionnaire on which patient tolerance was scored. Another
      questionnaire was completed by the endoscopist, recording quality of the
      preparation. From the 40 patients with a normal colon (19 Sen, 21 NSen) a biopsy
      was taken from the sigmoid colon and analyzed for morphological abnormalities. No
      difference could be demonstrated in tolerance or quality of bowel preparation
      between the two groups. A marked increase of mononuclear infiltrate in the lamina
      propria was observed in Sen compared to NSen: in 10/19 vs. 2/21 patients
      respectively, p < 0.0005. CONCLUSION: As these microscopic effects could hamper
      the interpretation of colonic biopsies, bowel preparation without sennosides is
      to be recommended.

PMID- 9531686
TI  - [Photodynamic therapy of early squamous epithelial carcinomas and severe squamous
      epithelial dysplasias of the esophagus with 5-aminolevulinic acid].
AB  - INTRODUCTION: Photodynamic therapy (PDT) is a new local, endoscopically
      controlled therapeutic concept based on the selective sensitization of malignant
      and precancerous lesions prior to light-induced tissue destruction. 5
      aminolaevulinic acid (5-ALA) appears to be a promising alternative
      photosensitizer with a high mucosa specificity without phototoxic side effects on
      the skin. We report on our experience with this new form of PDT in 24 patients.
      PATIENTS AND METHODS: Five females and 19 males (aged 50 to 79 years) with
      histologically proven high-grade dysplasia (n = 9) and early cancer (normal EUS
      or uTlNOMO, n = 15) of the esophagus were included in this study. Four to six
      hours after oral ingestion of 5-ALA (dosage of 60 mg/kg b.w.) laser light
      irradiation was conducted with a dye laser system (XP 800 KTP/YAG, Laserscope,
      San Jose, USA) at a wavelength of 635 nm. With a light dose of 150 J/cm2.
      RESULTS: The length of the segment with severe dysplasia or mucosal cancer varied
      between 0.5 and 9 cm (mean length: 3.6 cm). High-grade dysplasia was eradicated
      in all patients (9/9). In addition, 16 mucosal carcinomas in 15 patients were
      successfully treated in 8/16 cases with an average of 1.8 treatment sessions and
      a mean follow-up of 14.5 months (range: 3-31 months). A method-related mortality
      and morbidity was not observed. CONCLUSIONS: Severe dysplasia and superficial (<
      or = 2 mm) mucosal cancer of the esophagus can be completely ablated by 5-ALA
      PDT. Patients with early carcinoma thicker than 2 mm are not suitable for 5-ALA
      PDT. PDT with 5-ALA has few side effects and might offer an alternative to
      esophagectomy or radio-chemotherapy.

PMID- 9531687
TI  - [Neutropenic enterocolitis].
AB  - A 58-year old patient with metastasizing squamous cell carcinoma of the left lung
      developed fever, diffuse abdominal pain and profuse diarrhea while treated with
      paclitaxel and radiation therapy. A sigmoidoscopy was performed to exclude
      pseudomembranous colitis but showed multiple mucosal petechiae. Histologic
      examination disclosed neutropenic colitis. Conservative treatment was successful.

PMID- 9531688
TI  - A rare case of bloody diarrhea: thrombosis of the V. mesenterica inferior
      following laparoscopic cholecystectomy.
AB  - Laparoscopic cholecystectomy has become the standard treatment for symptomatic
      cholecystolithiasis. The most common complications, as current experiences show,
      are bleeding, bile duct injury and non-technical complications like pneumonia. In
      some individual cases ischemic lesions of bowel by injury or thrombosis of
      intestinal vessels are described. Here we report the rare case of intestinal
      venous thrombosis following laparoscopic cholecystectomy. The complication
      clinically appeared within 24 h after operation starting with bloody diarrhea and
      mimicking inflammatory bowel disease. The patient, a 41-year old man, was treated
      with high-dose heparin and could be discharged after 44 days without complaints.
      Coloscopy six months after the event showed a restitution ad integrum.

PMID- 9531689
TI  - [Significance of coinfection with hepatitis G virus for chronic hepatitis C--a
      review of the literature].
AB  - BACKGROUND: The clinical significance of the recently discovered hepatitis C
      virus (HGV/GB virus C (GBV-C) is not conclusively clarified. The aim of this
      analysis was to evaluate the frequency of HGV/GBV-C coinfection at existing
      hepatitis C infection, the significance for the course of the liver disease, and
      its response to antiviral therapy. METHODS: The literature available by medline
      and the PubMed Retrieval System as well as abstracts of recent German, European,
      and American conferences on liver diseases (GASL, EASL, ASSLU) concerning HCV/GBV
      C-coinfection were analyzed. RESULTS: We identified 66 references with 5,388
      patients suffering from HCV-infection. 941 (17.5%) were coinfected with GBV-C.
      Excluding some groups at risk (intravenous drug abusers, dialysis patients,
      patients after liver transplantation), the rate of coinfection varied
      significantly in respect to geography: 20.5% in European vs. 10.9% in Japan (p <
      0.0001). Additionally, coinfection occurred in 38% of intravenous drug users. The
      studies showed that coinfection was related to the frequency of blood
      transfusions. Furthermore, the parenteral transmission route of GBV-C was
      generally confirmed. Overall GBV-C does not seem to have any negative influence
      on the course of HCV-related chronic liver disease or the development of
      chronicity of acute hepatitis C infection, nor does it have any influence on
      histology, transaminase-levels or response of HCV to antiviral therapy; GBV-C was
      shown to be sensitive to interferon-alpha with a relapse rate up to 53%
      comparable to HCV. There is no correlation between response of HCV and GBV-C to
      interferon. CONCLUSION: This analysis of the published data concerning
      coinfection of HCV and HGV/GBV-C revealed no influence of GBV-C on the course of
      HCV-related liver disease (clinical, biochemical, histological). GBV-C does not
      modify the response rate of HCV to interferon-alpha, but GBV-C is sensitive to
      interferon with high relapse rates.

PMID- 9531690
TI  - [Autoantibodies in chronic inflammatory bowel diseases: more than an
      epiphenomenon?].

PMID- 9531691
TI  - [Hepatitis C: a cause for acute liver failure?].

PMID- 9531692
TI  - [Eradication of high-grade dysplasia in Barrett esophagus by photodynamic therapy
      with endogenously generated protoporphyrin IX].

PMID- 9531693
TI  - [Cardiomyocyte transplantation--a cell replacement for repair of myocardial
      infarction?].
AB  - Cardiomyocytes lose the ability to proliferate after birth. Subsequently,
      irreversible cellular damage, e.g., during myocardial infarction, causes loss of
      functional properties and cell replacement by fibrotic tissue. It is, therefore,
      not surprising that cell replacement strategies such as cardiomyocyte
      transplantation in damaged myocardium or scar tissue has gained widespread
      interest. In other species such as mice, rats, and dogs, the technical
      feasibility of skeletal myoblast-, satellite cell-, and fetal cardiomyocyte
      engraftment into normal and diseased myocardium has been demonstrated by simple
      injection methods. Repeatedly, it has been shown that transplanted cells may
      survive for weeks within host myocardium and build intercellular connections such
      as gap junctions and desmosomes. In contrast, grafthost connections have not, as
      yet, been convincingly demonstrated. Hypothetically, cell transplants might
      exhibit the following functional properties: stabilization of diseased tissue to
      prevent structural remodeling; carrier for recombinant proteins, growth factors
      or drugs to induce molecular alterations of host myocardium; and improvement of
      regional and global myocardial function due to active contractility. However,
      clear evidence of coordinated contractility of transplanted cells, and, thus, of
      a clinically relevant therapeutical use of cardiomyocyte transplantation as a
      replacement strategy for damaged host cardiac cells, remains to be demonstrated.

PMID- 9531694
TI  - [Improvement of aerobic capacity in chronic congestive heart failure. Which
      training method is appropriate?].
AB  - Standardized guidelines for exercise training for patients with chronic
      congestive heart failure (CHF) have not been established. In the past, CHF
      patients involved in exercise training studies demonstrated a wide range of
      cardiac and functional impairment, with an ejection fraction between 18 and 35%
      and a peak VO2 between 12.2 and 25.4 ml/kg/min on average. For determination of
      training intensity, a VO2 between 40 and 70% of peak VO2 and/or training heart
      rate between 60 and 80% of peak heart rate was used. There was also a wide range
      for frequency (between 3 and 7 times per week) and duration of training (between
      20 and 60 min per session). For aerobic exercise training only continuous
      training methods were applied. We have developed a new interval training method
      which allows intense exercise stimuli on peripheral muscles with minimal cardiac
      strain. After only three weeks of training, the improvement in aerobic capacity
      was similar to that reported after longer training periods using continuous
      methods. To determine work rate for work phases of interval training, a special
      steep ramp test was developed. By analysis of acute physical responses to this
      testing procedure and to the interval training, both were proven to be tolerable
      in CHF patients, even if their ejection fraction is as low as 13%, or peak
      cardiac index not greater than 1.61/m2/min, and peak VO2 less than 8.5 ml/kg/min.

PMID- 9531695
TI  - [Cheyne-Stokes respiration in patients with congestive heart failure].
AB  - Cheyne-Stokes respiration (CSR) during sleep is common in patients with severe
      congestive heart failure induces repetitive oxygen desaturation with arousals,
      and impairs sleep. This causes daytime symptoms and likely an increase in
      sympathetic activity. It has, therefore, been suggested that CSR is independently
      related to mortality. The major mechanisms behind CSR include reduced body stores
      of oxygen, a low apneic threshold for carbon dioxide, prolonged circulation time
      between the lung and the carotid body, and disturbance of respiratory control due
      to arousals. It is apparent that the main task in treating CSR is the therapy of
      congestive heart failure. Indeed, diuretics to treat pulmonary congestion as well
      as ACE-inhibitors reduce CSR. Recently, theophylline (an antagonist of the
      ventilatory depressant adenosine) was shown to reduce CSR and oxygen
      desaturation. Continuous positive airway pressure did improve CSR but not sleep
      and may reduce cardiac output in a subgroup of patients with heart failure.
      Nocturnal oxygen reduces CSR and improves exercise tolerance as well as sleep.
      This and its apparent safety makes oxygen an appropriate treatment for nocturnal
      CSR. Whether successful treatment of nocturnal CSR has any impact on the natural
      course of heart failure needs to be determined in further studies.

PMID- 9531697
TI  - [Twiddler-Syndrome in a subpectoral implanted unipolar cardioverter
      defibrillator].
AB  - Twiddler's syndrome is a rare complication in patients with pacemakers. We report
      this very rare syndrome in a patient with pectoral implanted unipolar
      cardioverter defibrillator. This syndrome was detected because the patient
      presented in the 3 month routine visit an exitblock with an increased pacing
      impedance. The defibrillation threshold remained unchanged. The chest x-ray
      revealed an inferolaterally migrated generator with a multiply rotated lead. The
      intraoperative exploration showed a generator which was rotated nine-fold around
      its longitudinal axis with a multiple twisted unipolar lead. The lead was
      substituted and the aggregate fixed with a suture to the underlying muscle
      fascia. An atrophy of the pectoralis muscle was found in this patient which
      previously resulted from a long hospital stay. This atrophy was identified as a
      possible risk factor for the development of Twiddler's syndrome. This report
      illustrates that Twiddler's syndrome, a rare complication in patients with
      pectoral ICD, may become a significant problem in these patients as it is for
      pacemaker patients but with more serious possible consequences.

PMID- 9531696
TI  - [The intraoperative measured stimulation impedance of pacemaker electrodes is not
      a predictor for their longevity].
AB  - As pacing impedance is inversely related to pacing current, the increase of
      pacing impedance additionally decreases pacing current. Whether the impedance
      measurement at implantation predicts the outcome during follow-up, was studied in
      87 patients who received the VDD-single lead UniPass 425 connected to the
      pacemaker Unity (Sulzer Intermedics). The impedance changes between implantation
      and 6 months follow-up were assessed for each patient. Similar impedance values
      were defined, if the two measurements were within a range < or = -100 to +100
      omega. Six-months impedance was lower or higher compared to implantation, if the
      difference exceeded > -100 or > +100 omega. At implantation, impedance was 535 +/
      98 omega (range: 333-811 omega) and significantly increased to 604 +/- 160 omega
      (range: 361-1150 omega) after 6 months. Mean difference between the two
      measurements was 69 +/- 162 omega (range: -336 bis + 560 omega). Similar
      impedance had 43 (implantation: 527 +/- 75 omega, 6 months: 531 +/- 87 omega),
      lower values 11 (implantation: 660 +/- 83 omega, 6 months: 494 +/- 73 omega) and
      higher values 33 patients (implantation: 503 +/- 99 omega, 6 months: 735 +/- 168
      omega). Compared to the patients with similar impedance patients with lower
      impedance had a significantly higher impedance values at implantation.
      CONCLUSIONS: Pacing impedance increased significantly within 6 months after
      implantation. Pacing impedance changed > 100 omega in 51% of the patients. The
      long-term follow-up of pacing impedance can be predicted generally, but not for
      the individual patient.

PMID- 9531698
TI  - [Therapy with implanted cardioverter-defibrillator: Is a replacement of the
      impulse generator due to battery depletion also necessary without the occurrence
      of a tachyarrhythmia episode?].
AB  - The aim of this retrospective study was to evaluate the necessity of the
      replacement of an implantable cardioverter/defibrillator (ICD) in patients with
      pulse generator battery depletion without an adequate, spontaneous arrhythmia
      episode during the life-time of the first implanted device. In this study 213
      patients with implanted ICDs were enrolled. In 62 patients an elective generator
      replacement due to battery depletion was performed. Both patient groups (Group A:
      patients with generator replacement n = 62 and Group B: patients without
      replacement n = 151) were not different with regard to main clinical
      characteristics, such as underlying heart disease and left ventricular function.
      In both groups there was a predominance of male patients (Group A: 89%; Group B:
      83%). The mean age was 58 +/- 11 years and 59 +/- 11 years in Group A and Group
      B, respectively. Coronary artery disease was present in 66% and 68% of the
      patients. There was a comparable left ventricular ejection fraction: Group A:
      30.5 +/- 9% vs Group B: 31.9 +/- 9%. The follow-up time was much longer in Group
      A patients compared to Group B patients (50.5 +/- 14 vs. 16.5 +/- 11 months). For
      the total patient group there was a 5 year event-free probability of 23%, no
      differences were found between both groups. The subanalysis in Group A patients
      revealed no difference in the probability of ICD-shock occurrence prior to or
      after the replacement of the pulse generator. In 48/62 (77%) of Group A patients
      adequate ICD discharges were documented. In 15/62 (24%) patients shock occurred
      before and after generator replacement. In 6/62 (10%) of Group A patients, the
      first adequate ICD-therapy was documented after generator replacement. The
      results of this study indicate the necessity of an ICD-pulse generator
      replacement even in patients without an adequate device discharge during the life
      time of the first implanted device.

PMID- 9531699
TI  - [Recanalization of Botalli's ductus arteriosus after catheter occlusion with a
      Rashkind double umbrella device].
AB  - Interventional duct occlusion with the Rashkind PDA occluder has become a
      widespread alternative treatment to surgery. Whereas residual shunting is well
      known, reopening of a completely occluded duct has been published in only 3
      cases. We report another case of a young adult in whom ductal shunting reappeared
      after he had restarted physical exercise and sports activities soon after the
      occlusion procedure. Recanalization might have been due to changing of the device
      position without embolisation. A second Rashkind PDA occluder was successfully
      implanted 6 months after the first procedure with complete closure of the
      residual shunt.

PMID- 9531700
TI  - [The influence of coronary artery dissection on long-term outcome after
      percutaneous transluminal coronary angioplasty].
AB  - The influence of a coronary dissection on long-term outcome after PTCA has been
      controversely discussed in the past. Whereas diverse experimental studies have
      shown a positive relation between dissection and the incidence of restenosis,
      clinical trials could not document an influence of dissection on long-term
      outcome. However, most of the trials did not distinguish between the different
      morphologic configuration of the vascular dissection. Thus, the aim of the
      present study was to determine the influence of dissections on restenosis in
      regard to their amount and morphologic configuration. The prognostic importance
      of the National Heart, Lung, and Blood Institute classification on dissection as
      well as the importance of an additional classification of angiographic
      complications after PTCA were investigated to determine possible pathophysiologic
      mechanisms of the restenosis process. The study included 141 consecutive patients
      with 143 stable dissections after PTCA. A follow-up study was performed 13 months
      in mean after successful PTCA, which included clinical, symptomatic, and
      functional aspects of patients. In this patient population, type C dissections
      (Dorros et al.) showed a relevantly increased risk of a clinical adverse event
      (41.0%), whereas patients with a type A dissection had only a small risk of an
      adverse event (10.0%) over the investigation period. Type B dissections revealed
      an intermediate risk (18.0%), and type D dissections showed a risk of 33.3% of an
      adverse event, which was lower than that observed for type C dissections. The AC
      classification of the postinterventional coronary morphology was a stronger
      predictor of an adverse outcome after PTCA (p = 0.0003) than was the Dorros
      classification (p = 0.0056). CONCLUSION: The grade of a coronary dissection was
      highly, positively related to an ischemic event after PTCA using both the Dorros
      and the AC-classification (p = 0.0056/p = 0.0003). In regard to the special
      association of the AC-class with the amount of vascular injury, we conclude that
      the amount and configuration of coronary dissection correlates with the long-term
      outcome after PTCA.

PMID- 9531701
TI  - [Accidental occlusion of the common femoral artery after Angio-Seal-application].
AB  - Removal of the arterial sheath immediately after PTCA is desirable for patients,
      reduces the medical staff's workload, and may decrease hospital costs due to a
      shortened length of stay. Although the safety and efficacy of the hemostatic
      systems used especially for the above purpose have been sufficiently documented,
      inadvertent intraluminal vascular occlusion is theoretically possible. While
      partial or complete arterial occlusion in conjunction with the VasoSeal collagen
      prototype device has been previously reported, similar complications occurring
      with the Angio-Seal device were not published. In this report, we describe a 54
      year old female patient (height: 150 cm, weight: 42.5 kg) who was transferred for
      PTCA following an acute anterior wall myocardial infarction. Immediately after
      PTCA, the Angio-Seal device was deployed utilizing standard technique. No
      difficulties were encountered during device deployment, however, immediately
      following device placement active arterial bleeding occurred. Due to the
      inadequacy of hemostasis, heparin was reversed with protamine to avoid further
      hemorrhagic complications. Following this, the desired hemostasis quickly
      occurred, but the patient soon complained about symptoms suggestive of an acute
      occlusion of the right femoral artery. Unsatisfactory attempts at lysis resulted
      in the patient being transferred to vascular surgery. The complete Angio-Seal
      system (anchor including collagen) was located intravascularly, and removed
      during surgery. This case report demonstrates that even an experienced examiner
      can inadvertently deploy the Angio-Seal completely intraarterially. In addition
      to the known contraindication, "peripheral arterial occlusive disease", we
      recommend that the Angio-Seal device not be utilized in patients of small
      physical size.

PMID- 9531702
TI  - [Intracoronary ultrasound during recanalization of chronic coronary occlusions:
      Relation to restenosis and reocclusion after balloon angioplasty or stent
      implantation].
AB  - Chronic coronary occlusions carry a high recurrence rate, and coronary stenting
      evolves as a preferred therapy of these complex lesions. Insight into the
      morphology of the occluded segment by intracoronary ultrasound may provide
      information which may help to improve the interventional strategy and the long
      term outcome. After successful recanalization of chronic coronary occlusions (4
      weeks to 33 months; median 3.2 months) in 59 patients, 29 patients were treated
      by balloon angioplasty alone, and 30 patients received one or more coronary
      stents because of complicated dissections or a high-grade residual stenosis after
      balloon dilatation. Intracoronary ultrasound was used to assess the lesion
      morphology and to quantify the angioplasty result. The luminal area, the total
      vessel area and the extent of the plaque burden were measured proximal and distal
      to the occlusion and at the narrowest site within the occlusion or the coronary
      stents, and the elastic recoil was calculated. Plaques in chronic occlusions were
      predominantly hypodense, and 44% were characterized by a multilayered plaque
      appearance. The elastic recoil was higher in multilayered plaques than in other
      plaques (46 +/- 19% vs. 34 +/- 15%; p < 0.05). Based on the quantitative
      ultrasound measurement after the initial balloon dilatation, it appeared that the
      initial balloon was undersized in 54%. The lumen area in patients with balloon
      angioplasty alone was increased from 4.02 +/- 1.34 mm2 to 5.49 +/- 1.47 mm2 and
      in the stented patients from 3.58 +/- 1.04 mm2 to 7.10 +/- 1.92 mm2. The
      recurrence rate in patients with balloon angioplasty was 48% with 24%
      reocclusions. Patients with recurrence had a slightly lower lesion area (3.97 +/-
      1.41 mm2 vs. 4.71 +/- 1.44 mm2; n.s.) and minimum diameter (1.82 +/- 0.31 mm vs.
      2.14 +/- 0.40 mm; p < 0.05) after dilatation. In stented patients the recurrence
      rate was 27% with two early stent thrombosis (6.7%) and no late reocclusion. In
      patients with recurrence the achieved stent area was significantly smaller than
      in those without restenosis (5.71 +/- 0.90 mm2 vs. 7.59 +/- 1.96 mm2; p < 0.01),
      and the degree of vascular remodelling at the site of the occlusion was less
      pronounced. Intracoronary ultrasound showed sonographic plaque characteristics in
      chronic occlusions which responded poorly to balloon dilatation alone. Stent
      implantation improved considerably the luminal area gain and could reduce the
      long-term outcome. To further improve the recurrence rate in stents, an optimized
      stent expansion should be achieved, and intracoronary ultrasound could provide an
      ideal tool for this purpose.

PMID- 9531703
TI  - [Concerning the work of K. Kroger++ and colleagues: Radial artery as an access
      for diagnostic coronary angiography].

PMID- 9531704
TI  - [Activity report for the "Clinical Pharmacology" Workgroup].

PMID- 9531705
TI  - [Plastic reconstructive surgical methods in breast saving therapy of breast
      carcinoma: our concept of modified quadrantectomy].
AB  - The conservative treatment of carcinoma of the breast pursued since 1987 at the
      Gynecological Clinic of St. Elisabeth's Hospital in Saarlouis has resulted in a
      steady increasingly in the application of local flapping techniques, tumor
      adapted reductive or mastoplastic procedures and latissimus dorsi flaps. A total
      of 446 breast tumors were removed by surgery and the breast preserved in 198
      cases (= 44.4%). In 151 of these, the plastic correction of the defect was
      performed simultaneously. Transposition flaps (37 cases), rotation flaps (28
      cases), modified reductive and mastoplastic techniques (71 cases), and latissimus
      flaps (15 cases) were applied, depending on the individual situation. In 22 cases
      a secondary operation was required: in 7 cases a mastectomy (5 cases of
      multifocal tumor growth, 1 flap necrosis during chemotherapy and 1 local
      recurrence), in 5 cases an excision biopsy owing to suspected recurrence with
      granuloma and in two cases a correction of the mamillary localization. 5 patients
      underwent an adaptive reduction of the healthy breast. The cosmetic results were:
      in 97 cases (65%) excellent or good, only 9 (6%) were evaluated by the operators
      as poor. Local recurrences were observed in 5 patients. These methods are
      intended to combine the oncological advantages of Veronesi's QUART principle
      (quadrantectomy, axillary dissection, radiation therapy) with improved cosmetics
      results, making it possible to operate larger tumors and smaller breasts with a
      satisfactory outcome.

PMID- 9531706
TI  - [Hormonal treatment of proximal tubal pathology with the GnRH analogue
      leuprorelin].
AB  - In proximal tubal occlusions (PTO) the microsurgical anastomosis or in case of
      extensive tubal damage the in vitro-fertilisation (IVF) are the treatment
      modalities of choice. Aim of our study was to evaluate the effectivity of GnRH
      analogues in the treatment of PTO. In 23 patients with repeatedly proven proximal
      tubal occlusion the GnRH-analogon Leuprorelin was applied for a 3 month period.
      20 out of 23 patients completed the entire study including a further tubal
      patency test. 10 patients showed open tubes on both sides and in 2 cases one
      oviduct was patent. In 8 patients no effect of the hormonal treatment was found.
      Following the therapy 4 pregnancies occurred, 2 were located ectopically.
      Regarding tubal patency we could demonstrate a significant effect of hormonal
      treatment in proximal tubal occlusions (PTO). However, in respect to the
      pregnancy rate the results were not satisfactory. Therefore, the hormonal
      treatment of PTO by GnRH-analogues is limited to certain cases and doesn't
      represent a standard therapy.

PMID- 9531707
TI  - [External fetal version from breech presentation to cephalic presentation:
      modifying factors, reliability and risks].
AB  - External cephalic version (ECV) was performed in 524 single pregnancies. The
      version was successful in 38.4%. Success is mainly influenced by parity, quantity
      of amniotic fluid and maternal weight. An emergency cesarean section was
      necessary in 0.6% because of fetal bradycardia. Compared to controls the ECV was
      not associated with the increase of a premature rupture of membranes,
      complications with umbilical cord or transfer of the child to the paediatric
      department. Also there was no difference in the pH or Apgar-ranges. One fetal
      death was diagnosed 17 days after ECV, the reason therefore remained unclear.
      There are existing a few other reports with similar cases. We conclude that ECV
      is a appropriate trial to convert the fetus into cephalic presentation, but
      because of possible complications precautions must be taken, e.g. that means to
      carry out the trial under conditions which allow immediate cesarean section and a
      frequent follow up of the woman until delivery.

PMID- 9531708
TI  - [Laparoscopic therapy of interstitial tubal pregnancy].
AB  - Interstitial pregnancy is life threatening and rarely operated laparoscopically.
      We report on the diagnostic and therapeutic endoscopic management using monopolar
      scissors, loop, suturing and bag harvesting.

PMID- 9531709
TI  - [Endoscopic management of uterine perforation with the ENDO-UNIVERSAL surgical
      stapler].
AB  - The management of an uterine perforation occurring during a D & C, in which a
      bleeding could not be stopped by coagulation per laparoscopiam is described. The
      closing of the bleeding injury in the uterus wall was performed by ENDO-UNIVERSAL
      clip-instrument. The wound was closed and the bleeding stopped. The possibility
      to manage an uterine perforation with this simple method is reported and
      discussed.

PMID- 9531710
TI  - Pregnancy in obstructive sleep apnoea syndrome under treatment with nCPAP.
AB  - We report on a patient with a diagnosed obstructive sleep apnoea syndrome (OSAS)
      who became pregnant during treatment with the nCPAP (nasal continuous positive
      airway pressure) apparatus, and gave birth. In the literature search we didn't
      find any similar case report. The present view on OSAS treatment with particular
      regard to the use of nCPAP is also presented. Through reviewing literature we
      analysed positive effects of this kind of treatment on mother and fetus. The
      negative aspects of nCPAP treatment are discussed.

PMID- 9531711
TI  - Prenatal diagnosis of an uncommon syndrome: thrombocytopenia absent radius (TAR).
AB  - The prenatal diagnosis of the thrombocytopenia absent radius (TAR) syndrome using
      ultrasound and cordocentesis at the 34th week of gestation is established. Two
      basic components of the syndrome, bilateral absence of radius and
      thrombocytopenia at a level 12.000/mm3 were detected. No complication during the
      cordocentesis and delivery occurred due to thrombocytopenia. This case report, to
      our knowledge, is one of a limited number of cases emphasized on prenatal
      diagnosis of TAR syndrome in the world.

PMID- 9531712
TI  - [Echinococcosis--case report and review of the literature].
AB  - Echinococcosis is a rare disease in central Europe. But with the increasing
      numbers of foreign citizens, this disease becomes more important in cases of
      cystic processes of unknown origin. It is still very difficult to achieve a
      diagnosis and a subsequent therapy, particularly in cases of multiple cysts,
      means a long lasting process containing certain risks. We report on a 20 years
      old female patient, suspected to have a severe inflammatory pelvic disease. We
      found multiple abdominal cysts, not originating from or involving ovaries, tubes,
      bowel, liver or kidneys. The serologic investigations proved our clinical
      suspicion on an echinococcosis. But neither serology nor clinical investigations
      could provide any indication on which kind of echinococcosis we found. We started
      a therapy with high doses of mebendazole to achieve a shrinkage of the multiple
      cysts to enable a surgery.

PMID- 9531713
TI  - [Pain therapy in multiple bone metastases in breast carcinoma with rhenium 186
      HEDP].
AB  - Therapeutic means for patients with disseminated painful bone metastases in
      breast cancer are strongly limited. There is a big need of an effective and well
      tolerated therapy. The aim of this study was to evaluate the efficacy of rhenium
      186 HEDP for pain palliation in patients with bone metastases in breast cancer.
      17 patients with painful bone metastases taking analgesics received one or more
      injections of 1295 MB9 rhenium-186 HEDP. In 59% of the patients the therapy
      resulted in a significant reduction of pain. The duration of pain relief
      partially hold on up to nine weeks. The main side effects of therapy were a short
      decrease of platelets and leucocytes and an increase of pain for 1-2 days. As
      conclusion we found out that therapy with rhenium-186 HEDP can be used
      complementarily to analgesic therapy and radiation in patients with painful
      disseminated bone metastases in breast cancer.

PMID- 9531714
TI  - [Congress organization and the internet--new structures in scientific
      communication for gynecology?].
AB  - For decades scientific sessions and conferences were a proven way to spread and
      exchange scientific results worldwide--not only in the field of medicine. With
      growing availability and accessibility of information on the internet and WWW
      conferences are now not only listed and announced on a multitude of websites, but
      also are prepared ahead from simple registration to online discussions. By means
      of selected examples information is provided on how keeping oneself informed
      about former or planned conferences by using the internet.

PMID- 9531715
TI  - [Research and education online--on the significance of the internet for
      scientific organization].

PMID- 9531716
TI  - [Molecular effects of a microbicidal substance on relevant microorganisms:
      electron microscopic and biochemical studies on povidone-iodine].
AB  - The microbicidal activity of the broad spectrum antimicrobial agent povidone
      iodine is due to the strong oxidizing effects of free iodine on functional groups
      of amino acids, nucleotides and double bonds of unsaturated fatty acids. While
      the chemical mechanism of action of PVP-iodine is well understood, the actual
      sequence of events on the cellular and molecular level that causes rapid cell
      death has not been fully understood. The aim of this study was to elucidate
      effects of povidone-iodine on cell ultrastructure by electron microscopy and to
      monitor changes in enzyme activity and nucleotide efflux. Staphylococcus aureus,
      E. coli and C. albicans, medically relevant gram-positive, gram-negative and
      yeast micro-organisms, served as models. In the presence of povidone-iodine,
      rapid partitioning of the cytoplasm and pronounced coagulation of nuclear
      material was noted. Especially C. albicans exhibited a rapid, dose-dependent
      "loosening" of the cell wall; cells remained intact without lysis, rupture or
      wall breakage. Changes in beta-galactosidase and nucleotide concentrations were
      measured in E. coli. A rapid and dose-dependent loss of cellular beta
      galactosidase activity was found, with no increase in the supernatant; loss of
      cellular nucleotides corresponded with an increase in the supernatant. Electron
      microscopy and biochemical observations support the conclusion that povidone
      iodine interacts with cell walls of micro-organisms causing pore formation or
      generating solid-liquid interfaces at the lipid membrane level which lead to loss
      of cytosol material, in addition to enzyme denaturation. The chemical mechanism
      of action explains the fact that povidone-iodine does never generate resistance
      in micro-organisms.

PMID- 9531717
TI  - [Antibacterial effectiveness of povidone-iodine (Betaisodona) against highly
      resistance gram positive organisms].
AB  - Antiseptics that are locally applicable gain in significance due to their
      reliable microbicidal effectiveness and especially due to the rising incidence of
      highly resistant bacteria. This is because systemically applied antibiotics are
      not sufficient in eradicating superficial mucodermal bacteria and locally applied
      antibiotics can cause new resistance rapidly. The aim of this study was to
      demonstrate the microbicidal effectiveness of Poly(1-vinyl-2-pyrrodlidon)-iodine
      (PVP-iodine) against ten genotypical different methicillin resistant
      Staphylococcus aureus-(MRSA-) and five Enterococcus faecium-strains in a
      quantitative suspension test. The effectiveness of PVP-iodine with protein load
      (0.2% and 2% albumin) was tested against three MRSA strains. Without any protein
      load best microbicidial activity (KRt-value > 5) was obtained with concentrations
      in the range between 1-10% of the original Betaisodona solution after 30s
      exposure time. With protein load (0.2% albumin) the optimum in microbicidal
      effectiveness shifts to concentrations > or = 10% Betaisodona solution referring
      to an exposure time of 30s. With a protein load up to 2% albumin and an exposure
      time of 30s the bactericidal activity of the undiluted Betaisodona solution is
      already satisfying, while the 10% solution is not active till an exposure time of
      5 min. Summing up PVP-iodine is recommended as a local mucodermal antiseptic
      against highly resistant gram positives.

PMID- 9531718
TI  - [Antiseptic efficacy and acceptance of Octenisept computed with common antiseptic
      mouthwashes].
AB  - The efficacy of common antiseptic mouth rinses was evaluated in a study with
      healthy volunteers. Octenisept and Cetylpyridiniumchlorid had a significant
      stronger impact on the microbial burden of the oral cavity than Chlorhexidin
      (Corsodyl) immediately and 10 min after the application. Dobendan (contains
      Cetylpyridiniumchlorid) showed a better antimicrobial effect than Corsodyl
      immediately after application, after 10 min an increasing loss of efficacy was
      noted. The antiseptic efficacy of hexetidin-based Gurfix was very similar to the
      efficacy observed with Corsodyl from the start of the antiseptic treatment until
      1 h later. Acriflavine-solution (0.2% m/v) was significantly less efficient after
      10, 30 and 60 min compared to Corsodyl. The antimicrobial impact of Fluomint
      Lysoform was very similar to the effect of rinsing with dest. sterile water. A
      subjective assessment of taste and smell of the mouth rinse solutions concludes
      the evaluation. Further methodological aspects for a common test guideline for
      antiseptic mouth rinse solutions are discussed.

PMID- 9531719
TI  - [Inactivation of chlorhexidine for in vitro testing of disinfectants].
AB  - An insufficient neutralization of chlorhexidine (4%), tested in vitro against
      Enterococcus faecium ATCC 6057, was suspected in the quantitative suspension test
      although the combination Tween 80, cysteine, histidine and saponine was assessed
      as sufficient for neutralising chlorhexidine. Bactericidal activity of each
      neutralising compound and their combinations was excluded. Sufficient
      neutralization was observed when all dilution steps and the corresponding agar
      plates were supplemented with the neutralising compounds. Successful
      neutralization in broth is not equivalent with successful neutralization in
      tryptic saline. We suggest to supplement at least the agar plates of the first
      dilution step with neutralising compounds when testing chlorhexidine.

PMID- 9531720
TI  - [Effect on the microbicidal efficacy of formaldehyde, glutardialdehyde, peracetic
      acid, chloramine T (N-chloro-4-toluenesulfonamide), m-cresol, ethanol and
      benzyldimethyldodecacylammonium bromide by blood (model experiments for chemical
      disinfection of instruments)].
AB  - In a preceding paper (Zbl. Hyg. 191 [1991] 457-477) we reported on the dependence
      of the microbicidal efficacy of active agents of the disinfection of instruments
      on the amount of coagulated blood adhering to the instruments. In the present
      investigation, we were interested in the dependence of the microbicidal effects
      on the amount of blood in the solutions of the active agents. Test areas of 2 cm2
      were contaminated with 50 and 100 microliters coagulating blood, respectively,
      containing cells of Staphylococcus aureus as test germ. The solutions of the
      microbicidal agents were contaminated with heparinized blood up to a
      concentration of 4% immediately before starting the disinfection and 24 hours
      before, respectively. After a period of action lasting 1 hour at 20 degrees C,
      the relative number of test germs capable of multiplying (N/N0) was determined.
      The concentration of the microbicidal substances reducing the relative number of
      test germs capable to multiply to 10(-4) served for estimating the dependence of
      the microbicidal efficacy of the agents on the blood content of the solutions.
      The experimental results depended on the thickness of the layer of coagulated
      blood. The dependence of the efficacy of the microbicidal substances on the blood
      content of the solutions was the higher the thinner the blood layer was. At a
      thickness of the layer of the coagulated blood of 0.25 mm, a blood content of the
      solution of 4%, and applying it immediately after adding the blood, the
      concentration of glutardialdehyde had to be 1.6 times that without blood to reach
      the same microbicidal efficacy. When applying the solution 24 hours after adding
      the blood, the concentration of glutardialdehyde had to be 4.2 times that without
      blood. The quaternary ammonium compound reacted faster with the blood than did
      glutardialdehyde; the respective factors were 2.6 and 4.5. The concentration
      factors of chloramine T were 3.3 and 3.8. Under the conditions of the test,
      peracetic acid exhibited small concentration factors: 1.3 and 1.6. The
      microbicidal efficacy of ethanol, formaldehyde and m-cresol soap solution was not
      or only slightly altered by the amount of blood in the solution of the
      microbicidal agent.

PMID- 9531721
TI  - [Effect of protamine on the microbicidal efficacy of formaldehyde].
AB  - Testing the ability of commercial compounds to provide an effective disinfection
      of instruments requires test conditions that are close to reality which includes
      the proper selection of the material used to contaminate the test objects. The
      adhesion of the material must be strong enough to keep it attached to the test
      object during and after insertion into the disinfectant solution. Its
      characteristics should come as close as possible to those of the contaminations
      encountered in practice. The guideline for instrument disinfectants published by
      the Robert Koch-Institute recommends the use of coagulated blood. Accordingly,
      heparinized sheep blood is mixed with the test germs, and protamin is added to
      initiate coagulation. In the present investigation we compared this contamination
      procedure with a second one, in which coagulation was achieved by adding a CaCl2
      solution to citrate blood. We also included agarose as an almost inert
      contaminant in our experiments. The results showed that protamine is able to
      increase the microbicidal efficacy of formaldehyde on staphylococci
      significantly. When these test germs were embedded either in citrat blood or in
      agarose, it took about twice the disinfectant concentrations to achieve the same
      microbicidal effects as with protamine blood (Fig. 1). Remarkably, the results
      obtained with citrate blood were the same as those with agarose, regardless of
      the differences in material between the two contaminants. It should also be noted
      that the microbicidal effect of the formaldehyde proved to be almost independent
      from the amount of contaminant per test area, hence, from the thickness of the
      layer. When M. terrae was employed as test germ, the results obtained with
      protamine blood and citrate blood, respectively, as contaminants were identical
      (Fig. 2). The same was true for the other test germs investigated, except for E.
      faecium (Fig. 3). The addition of even very small amounts of protamine to the
      embedding compound, agarose led to a substantially increased efficacy of the
      formaldehyde against staphylococci (Fig. 4). This effect was especially distinct
      in suspension (Fig. 5). Whenever the efficacy of formaldehyde-containing
      disinfectants is to be tested and evaluated, one should be aware of this
      synergism between protamine and formaldehyde. In these cases, it is advised to
      employ other contaminating agents, such as coagulated blood prepared by addition
      of CaCl2 to citrate blood.

PMID- 9531722
TI  - [Irritating effects of disinfection by-products in swimming pools].
AB  - Compounds which can occur as disinfection by-products (DBP's) in swimming pool
      water were examined for their mucous membrane irritating potential. Previous
      studies using the rabbit eye test (Draize test) have shown that the irritating
      potential of typical concentrations of free and combined chlorine are
      insufficient to explain the degree of eye irritation that can result from
      exposure to swimming pool water. Other DBP's which may be responsible for eye
      irritation include halogenated carboxyl compounds (HCC's) which act as precursors
      during the formation of chloroform. In this study, a modified HET-CAM Test (Hens
      Egg Test at the Chorion Allantois Membrane) has been used to investigate the
      mucous membrane irritating effects of HCC's. Some of the compounds tested were
      found to have a significantly increased irritating effect when compared to a
      chlorine/chloramine mixture of the same concentration, several mixtures of HCC's
      where even more active at lower concentrations than single compounds. However,
      the irritating effects of individual compounds as well as of mixtures of HCC's
      were not sufficiently intense to allow the identification of those compounds
      specifically responsible for the overall observed increase in irritation. HCC's
      were therefore tested in the presence of aqueous chlorine solution. When combined
      with aqueous chlorine, a number of compounds exhibited significantly enhanced
      effects. Our results show that the eye irritating effects of low concentrations
      of DBP's can be investigated using a modified HET-CAM assay. Moreover, results
      obtained using this assay suggest that the mucous membrane irritating potential
      of swimming pool water is a consequence of the effects and synergistic action of
      a number of DBP's in the presence of chlorine. Further work should be carried out
      in order to establish an indicator for eye irritating effects of swimming pool
      water.

PMID- 9531723
TI  - [Exposure of the population to volatile organic compounds inside an automobile
      and a subway train].
AB  - Air quality, in particular in urban regions, is affected by the emissions of the
      traffic and meanwhile for some substances motor vehicles became the dominating
      source. For valid quantitative risk assessment of the general population it is
      necessary to have informations about the main routes of exposure. Therefore in a
      pilot study 1994 and two times in summer 1995 and winter 1996 aromatic
      hydrocarbons, carbon monoxide (CO) and carbon dioxide (CO2) were determined under
      different meteorologic conditions inside of a car (a two year old VW-Golf with a
      three-way catalyst) and in a subway-train. The car route followed the subway (31
      km underground) and crossed the central parts of Berlin in streets with high
      traffic density. The mean values for benzene obtained during the three
      measurement periods inside the car were 21.1/21.5 and 21.6 micrograms/m3 (daily
      maximum: 31.9/26.3 and 35.0 micrograms/m3) and inside the subway 8.4/5.4 and 7.4
      micrograms/m3 (daily maximum: 16.0/7.4 and 10.3 micrograms/m3). The mean levels
      of CO in the car were 6 ppm (summer) and 5 ppm (winter) respectively, with peak
      concentrations of 33 and 70 ppm (10-minutes maximum). In the subway the values
      were 2 ppm (summer and winter); (10-minutes maximum: 5 and 12 ppm). A comparison
      between the two types of traffic shows three times higher concentrations of
      benzene inside the car. Our results demonstrate that the exposure of car
      occupants to benzene has to be taken into account for risk assessment. The
      concentration of CO inside the car is three to four times higher than in the
      subway train. Compared with other studies we found only low concentrations of CO
      inside the car.

PMID- 9531724
TI  - [Biological monitoring during exposure to the anesthetics isoflurane and
      sevoflurane].
AB  - Exposure to traces of inhaled anaesthetic agents may impair the health of the
      operating theatre personnel. Although no cause-effect relationship has been
      found, most public health authorities recommend various occupational exposure
      standards to minimize possible health risks. If metabolites of the substances are
      known, biological monitoring is an alternative to the monitoring of the operating
      theatre's air. The new anaesthetic agent Sevoflurane is considerably more
      transformed to fluoride than Isoflurane. Concerning fluoride there exist
      Biological Tolerance Values of 4.0-7.0 mg fluoride (F-) per gram creatinine
      (Crea). The aim of our study was to compare the fluoride excretion under the
      occupational exposure to sevoflurane and isoflurane. By the means of a direct
      reading instrument trace concentrations of sevoflurane, isoflurane, and nitrous
      oxide were measured during 40 anaesthetic procedures. Urine samples were
      collected before (Z1) and after the workshift (Z2), and in the morning of the
      next day (Z3). The analysis was done by the means of an ionselective electrode.
      The personnel-related concentrations (median, range) were 0.50 (0.16-7.04) ppm
      isoflurance and 27.36 (5.87-467.10) ppm nitrous oxide, and 0.79 (0.15-1.95) ppm
      sevoflurane and 17.74 (2.45-84.20) ppm nitrous oxide. The resulting fluoride
      values presented at Z1, Z2, and Z3 as median (range) during exposure to
      isoflurane were 0.15 (0.11-0.53), 0.19 (0.11-0.53), 0.20 (0.11-0.31) mg F-/g
      Crea, and 0.15 (0.10-0.46), 0.22 (0.13-0.44), 0.23 (0.15-0.69) mg F-/g Crea
      during exposure to sevoflurance, respectively. The trace concentrations were
      clearly under 10 ppm for the volatile substances and 100 ppm for nitrous oxide.
      The values are comparable to data recorded under similar working conditions. The
      measured fluoride values were low and remained under the legal tolerance values.
      Under the described conditions potential health risks were low.

PMID- 9531725
TI  - [Mutagenicity of mixtures of halogenated aliphatic hydrocarbons and polycyclic
      aromatic hydrocarbons in the Ames test with TA98 and TA100].
AB  - Within the framework of the assessment of the genotoxic potential of environment
      samples the Salmonella-microsome-test (Ames-test) is often used as a screening
      test. It is one of the most applied biotest systems and possesses a large
      scientific acceptance. Because most environment samples are mixtures of various
      substances, possible effects resulting from the combination should be taken into
      account with regard to the mutagenic potential. In this context we investigated
      eight polycyclic aromatic hydrocarbons each combined with six halogenated
      aliphatic hydrocarbons as to their mutagenicity in the Salmonella-microsome-test
      with TA98 and TA100. For an exogenous metabolizing system, Arochlor 1254 induced
      rat liver S9-mix was used. Benz-a-pyrene in combination with bromodichloromethane
      (Ames neg. in TA98 and TA100 +S9) showed an increase in the number of the
      revertants up to 25% in TA98 and TA100 (+S9). Carbon tetrachloride (Ames neg. in
      TA98 and TA100 +S9) showed in TA100 (+S9) an increase in the number of the
      revertants of 18% at most. In the combination 3-methylcholanthrene with
      dichloromethane the number of revertants in TA98 (+S9) increased by 25% and in
      TA100 (+S9) by 18%. Hexachloroethane (weakly mutagenic in TA98 +S9) in
      combination showed in TA98 (+S9) a slightly increased number of revertants with
      benz-a-pyrene as well with 3-methylcholanthrene. All the other substances tested
      (chrysene, phenanthrene, anthanthrene, dibenz-a, i-pyrene, triphenylene,
      fluoranthene) in combination with either tetrachloroethylene or trichloroethene
      did not cause an increase in mutagenicity.

PMID- 9531726
TI  - [Campylobacter spp. in the surroundings of poultry meat production-- incidence
      and chinolone resistance].
AB  - The incidence of Campylobacter in poultry meat production and in poultry meat
      gives cause for increasing concern in this field. Results of studies about
      clinical cases of Campylobacter in humans show a growing tendency. With poultry
      and foal mainly C. jejuni and C. coli are isolated, while C. jejuni has been
      identified as one of the most frequent bacterial pathogens of enteritis in humans
      also. Of altogether 509 samples from poultry herds, 209 isolates (41.1%) were
      Campylobacter positive. Tests in slaughter-houses showed that there are various
      factors that influence the contamination of the carcass during the process of
      slaughtering. The number of positive cases with chicken carcass is about 45.9%
      which is higher than with the animals, flocks. Of 52 pheasants 25.9% were
      Campylobacter positive. During the last 3 years Campylobacter isolates showed a
      growing Chinolone resistance (19.14% in butchered roast chicken and 28.5% in
      pheasants.

PMID- 9531727
TI  - Epidemiological study of intestinal helminthiasis in a Marrakech raw sewage
      spreading zone.
AB  - It has been suspected for some time that raw sewage is a potential source of
      protozoan and helminthic infections (10). Shuval et al. (16, 17) and W.H.O. (21)
      have shown that irrigating crops with untreated wastewater causes significant
      intestinal infections in both consumers and farm workers. This study compared the
      stools of "sewage farming" children exposed to raw sewage (El Azzouzia area) and
      those of a control group. Stool specimens from 253 exposed children and 275
      controls were analyzed. 73% of the exposed were infected with one or more
      helminths verses 30% of the control group. The main parasites were Ascaris and
      Trichuris. The El Azzouzia children were more heavily infected and their
      polyparasitism index (PPI: 13%) was considerably higher than that of the controls
      (PPI: 2%). Thus "sewage farming" children are exposed to detectable risk from the
      parasitic nematodes in raw sewage.

PMID- 9531728
TI  - [Anal hygiene in perianal skin diseases--compatibility of water moist and dry
      toilet paper].
AB  - The most common morphological changes in 485 of our ambulatory patients were
      found on external examination of the anal region (46%). These changes included
      erosions, fissur and eczema. Regarding the symptoms the predominant complaints
      were itching and burning in 42.1%. Anal hygiene after defaecation was most
      commonly done with dry toilet-paper (55%). A change in anal hygiene after
      defaecation relieves symptoms: By changing from water to moist toilet paper in
      9%, from dry toilet paper to moist toilet paper in 30%, from moist toilet paper
      to water in 32%, an from dry toilet paper to water in 60%. These results confirm
      known facts regarding the influences of conserving agents an printing materials
      in dry (often recycled) and moist toilet papers on the skin. These side-effects
      to be even more pronounced in the compromised skin and suggest that anal hygiene
      should be done with water only.

PMID- 9531729
TI  - Detection of psychotrophic aeromonads in drinking water.
AB  - In the context of evaluating their pathogenic relevance, culture on solid media
      is the only approach presently suitable for culture of psychotrophic aeromonads
      from drinking water. In this respect, a check must be effected to ensure that the
      culture medium cannot engender selective culture losses for individual species.
      For this reason, media to which e.g. ampicillin has been added are unsuitable.

PMID- 9531730
TI  - [Modern trends in the treatment of hypertension].
AB  - The main problem of treatment of hypertension in this country as well as abroad
      is the fact that only less than one quarter of hypertensive patients are treated
      effectively and have thus normal blood pressure readings. More effective
      treatment of hypertension is thus one of the main tasks of health care systems in
      different countries. The objective of treatment of hypertension is to achieve a
      normal blood pressure. Evidence has been provided that diuretics and beta
      blockers markedly reduce cerebrovascular and cardiovascular mortality, in
      particular in the elderly. ACE inhibitors are the drugs of choice in patients
      with heart failure or asymptomatic left ventricular dysfunction and in patients
      with diabetic nephropathy. Unsuitable for treatment of hypertension are short
      acting calcium channel blockers, in particular nifedipine. On the other hand,
      long-acting calcium channel blockers reduce the cerebrovascular mortality in
      elderly hypertensive patients. A number of questions still remain the subject of
      research: a) should diastolic pressure be reduced to values lower than 90 mm Hg;
      so far it is necessary only in hypertensive subjects with diabetes mellitus and
      in juvenile hypertensives; b) is the influence of new groups of antihypertensive
      drugs, in particular calcium channel blockers, similar, better or worse than that
      of diuretics and beta-blockers in the prevention of cardiovascular and
      cerebrovascular morbidity and mortality?; c) is it wise to recommend
      acetylsalicylic acid also to hypertensive patients without clinical signs of IHD
      or atherosclerotic affection of other vessels?; d) what is the value of combined
      antihypertensive and hypolipidaemic pharmacological treatment? Will this
      combination be not much more valuable in the prevention of IHD?; e) is the
      prognosis of hypertensive subjects with left ventricular hypertrophy better when
      ACE inhibitors are used as compared with other antihypertensive drugs?; f) do ACE
      inhibitors influence the prognosis of diabetic patients more favourably than beta
      blockers?

PMID- 9531731
TI  - [Smoking and diabetes mellitus].
AB  - Diabetic patients die mostly from chronic vascular complications, in particular
      ischaemic heart disease (specially type II diabetics) and renal failure
      associated with diabetic nephropathy (in particular type I diabetics). Smoking-
      one of the basic risk factors of atherosclerosis and its complications-
      accelerates in diabetics the atherosclerotic process and enhances the risk of
      cardiovascular complications. Smoking causes endothelial dysfunction, as well as
      deterioration of diabetic nephropathy and retinopathy. Smoking accelerates by
      various mechanisms the coagulation process and causes thus deterioration of the
      hypercoagulation state in diabetics. Anti-smoking intervention should be along
      with a diabetic diet the basic step in non-pharmacological treatment of
      diabetics.

PMID- 9531732
TI  - [Laboratory findings and serum levels of amyloid A and soluble interleukin-2
      receptors in patients with renal amyloidosis].
AB  - BACKGROUND: Renal amyloid involvement results either from primary or secondary
      amyloidosis. Extent of amyloid tissue deposition in kidneys and clinical course
      depends not only on the type of basic process but reflects also time of diagnosis
      and possibility to influence the basic process. METHODS AND RESULTS: We analyzed
      laboratory and clinical data of patients with bioptically proven renal
      amyloidosis. We found renal amyloidosis in 27 patients from an overall number of
      750 renal biopsies (RB) performed in our department (i.e. 3.6%). AA amyloidosis
      was diagnosed in 16 pts, AL amyloidosis in 11 pts. About 50% of patients had
      laboratory signs of nephrotic syndrome, all patients had various degree of
      proteinuria. Impaired renal function were found in more than 50% of patients, in
      6 of them we had to start renal replacement therapy. 8 pts died. Complications of
      severe nephrotic syndrome were the causes of death in majority of cases. We have
      started investigation of some amyloid precursors and cytokines in patients with
      AA and AL amyloidosis. We compared the results with group of patients with
      vasculitis. We investigated plasma and urinary levels of SAA (serum AA) and
      soluble receptor for interleukin 2 (sIL-2R). CONCLUSIONS: Clinical features and
      laboratory findings in our patients with renal amyloidosis approximately are in
      accordance with literary data. Plasmatic level of SAA was increased not only in
      the group of patients with AA amyloidosis, but also in the group of vasculitis.
      Urinary sIL-2R was significantly increased in patients with AA amyloidosis in
      comparison with healthy controls.

PMID- 9531733
TI  - [DNA polymorphism, allogenic bone marrow transplantation and peripheral cell
      chimerism].
AB  - BACKGROUND: Bone marrow transplantation or transplantation of peripheral stem
      cells is an effective treatment of a number of diseases. Its increasing success
      and expanding use in associated with the development of molecular diagnostic
      methods which enable to follow up the graft from its engraftment in a recipient
      and then during the whole posttransplantation period at the level extremely small
      numbers of cells. METHODS AND RESULTS: In peripheral blood of patients, genotypes
      of the following loci were examined by polymerase chain reaction (PCR): APOB,
      COL2A1, D17S20, D1S80, HVR/1G, SRY and AMXY. Technique of restriction analysis
      was used for loci DXYS20 and DXYS75. 1. The first signs of donor bone marrow
      activity were observed in 50% of patients already at the beginning of the second
      week after transplantation, while in the second half of patients increasing
      number of donor cells in peripheral blood was noticed in the second and third
      week. 2. Engraftment with full and permanent substitution of own bone marrow
      without presence of recipients cells in peripheral blood--complete chimerism--was
      achieved only in a part of patients (cca 50%). 3. Peripheral blood of other
      patients did not contain only donor cells but also recipients cells--mixed
      chimerism. With regard to its onset, the authors have divided mixed chimerism
      into early and late, taking into account that some patients can develop both
      types. In patients under study, early chimerism was found more frequently, which
      apparently resulted from a shorter period of observation of lately transplanted
      patients. 4. In cases of oncohaematologic patients, which allowed to study
      specifically the presence of a pathologic clone, the follow-up of chimerism
      enabled to distinguish between relapse of the original disease and "biologic"
      recovery--resurrection of original disease-free haematopoiesis. 5. Regression of
      mixed chimerism was supposed to be the result of treatment focused at the
      original disease (CML), in some patients, however, it was a spontaneous process.
      CONCLUSIONS: Follow-up of cellular chimerism in transplanted patients by means of
      molecular genetic methods provides substantial information about patient's shape
      which can be utilized it is necessary to decide on treatment procedures. For this
      reason it is desirable that examination of chimerism by molecular methods should
      form integral part of care of these patients.

PMID- 9531734
TI  - [Growth hormone deficiency and its treatment in adults].
AB  - Deficiency of growth hormone produced in the pituitary is manifested not only in
      children by impaired growth but also in adults. It is encountered most frequently
      in adults after surgery or irradiation in the hypothalamo-pituitary area, less
      frequently in idiopathic disorders of growth hormone production and secretion,
      either isolated or in conjunction with other trophic pituitary hormones. The
      diagnosis of growth hormone deficiency must be assessed by dynamic stimulation
      tests: most frequently the insulin stimulation test is used. Growth hormone
      deficiency in adult age is manifested by various non-specific symptoms which
      resemble symptoms (manifestations) of ageing: increase of adipose tissue,
      deterioration of lipid metabolism, osteopenia, impaired cardiac output and
      others; the symptoms recede partly if growth hormone is administered for a
      prolonged period. Clinical trials which are under way should define not only
      suitable indications but also ways of administration of this expensive treatment.

PMID- 9531735
TI  - The acting site of bronchodilator, methacholine and upper respiratory tract
      infection on airways.
AB  - BACKGROUND: The bronchodilator agent is an important drug for patients with
      chronic obstructive pulmonary disease. Methacholine is a popular bronchial
      provocative agent. Although the major acting site of bronchodilator, methacholine
      and upper respiratory tract infection (URI) has been evaluated in some studies,
      the sites are still in debate. This study investigated the exact major acting
      sites. METHODS: Thirty subjects participated in this study. Episodes of URI were
      identified by a questionnaire. Spirometry, bronchial provocative test with
      methacholine, and five minutes' inhalation of a mixture of helium and oxygen
      (HeO2) were done on day one. Spirometry, bronchodilator test, with five minutes'
      inhalation of HeO2 and expiratory flow-volume (F-V) curve were performed on
      another day. The change of pre- and post-HeO2 VEMax50 was calculated as delta
      VEMax50. The pre- and post-bronchodilator VEMax50 and delta VEMax50 differences
      were counted to decide the acting site of bronchodilator. After bronchial
      provocative test with methacholine, the volume of isoflow (VisoV) was estimated
      from pre- and post-HeO2 F-V curve to establish the acting site of methacholine.
      RESULTS: This study indicated that small airways are the major acting sites of
      bronchodilators, large airways are the major acting sites of methacholine and URI
      affects mainly large airways. Although airway hyperresponsiveness is more severe
      in subjects with positive methacholine response, the recovery of spirometry
      values is not significantly different between the methacholine-positive and 
      negative groups. CONCLUSIONS: The major acting sites of the bronchodilator,
      methacholine, and URI are the small, large and large airways, respectively.
      Bronchial hyperresponsiveness is not a cause of quick restoration of spirometry
      values in subjects with positive methacholine response.

PMID- 9531736
TI  - Effect of preoperative transdermal ketoprofen on post-hysterectomy pain.
AB  - BACKGROUND: In an attempt to reduce central sensitization after tissue injury,
      the concept of "pre-emptive analgesia" was evolved. The aim of the present study
      was to evaluate the analgesic effect of pre-incisional transdermal ketoprofen on
      post-hysterectomy pain. METHODS: Sixty patients scheduled for elective trans
      abdominal total hysterectomy were divided into three groups. The day before
      surgery, patients in Group 1 received transdermal ketoprofen 30 mg over the
      proposed surgical area twice; patients in Group 2 received a placebo patch under
      a similar design; patients in Group 3 received transdermal ketoprofen 30 mg over
      right thigh twice. Operations were performed under general anesthesia.
      Postoperatively, patients received patient-controlled analgesia with morphine for
      pain relief, and pain was assessed by visual analogue pain scale (VAS).
      Hemodynamic parameters, respiratory rate, sedation scale, morphine consumption
      and associated side effects were also recorded. RESULTS: There was no significant
      difference among groups with respect to VAS, sedation scale, blood pressure,
      respiratory rate or morphine consumption within 24 hours postoperatively. The
      mean time for first morphine demand was significantly delayed in Group 1 patients
      (p < 0.05). The incidence of nausea and vomiting among the three groups showed no
      significant difference. CONCLUSIONS: It seems that pre-incisional transdermal
      ketoprofen (30 mg, twice the day before surgery) has only a limited pre-emptive
      effect on post-hysterectomy pain as indicated by delayed first morphine request.
      Further, it had no effect on postoperative VAS, morphine consumption or incidence
      of nausea and vomiting.

PMID- 9531737
TI  - Klebsiella pneumoniae meningitis: analysis on clinical features of thirty-two
      adult patients.
AB  - BACKGROUND: To assess the clinical features and therapeutic outcomes of adult
      Klebsiella pneumoniae (KP) meningitis. METHODS: Thirty-two adult patients with KP
      meningitis were included in this study. Their clinical features, the outcomes
      with the third generation cephalosporin (moxalactam, cefotaxime, ceftazidime)
      treatment and prognostic factors were analyzed. RESULTS: These patients' diseases
      were predominantly community-acquired. Males outnumbered females (3:1). Diabetes
      mellitus (DM) was the most common underlying disease, followed by other
      debilitating diseases such as liver cirrhosis, neoplasm and end-stage renal
      disease (ESRD). Patients with spontaneous meningitis had a more fulminant course
      with a higher prevalence of bacteremia, shock and death (66%). Metastatic septic
      abscess was frequent (19%). Among the 21 patients who received initial
      appropriate antimicrobial therapy (IAAT), 2 took cefotaxime and 1 died; 13 took
      moxalactam of whom 5 died; and 6 took ceftazidime of whom 3 died. All of the
      other 11 patients who did not receive IAAT died. CONCLUSIONS: The clinical
      features of KP meningitis are various and indistinguishable from other form of
      bacteria meningitis. Most of the patients with KP meningitis are associated with
      underlying medical problems, such as diabetes mellitus and liver cirrhosis. Many
      factors, including septic shock, bacteremia, high cerebrospinal fluid lactate
      concentration, and IAAT, might influence the prognosis. In spite of a high
      mortality rate, however, IAAT is mandatory to improve the overall survival rate.

PMID- 9531738
TI  - Family caregivers' priorities for home care: a need assessment study.
AB  - BACKGROUND: Many studies have demonstrated that patients prioritize some
      attributes of health care over others. However, little effort has been devoted to
      measure which service attributes are most important to consumers, regardless of
      their satisfaction, in the field of home care. Moreover, home care requires
      family members to participate as caregivers. Thus, evaluating the needs of family
      caregivers who also provide home care should provide an opportunity to envision
      an effective home care system. METHODS: This study was designed to measure family
      caregivers' need for auxiliary home care services by examining their priorities
      for attributes of home care services. The respondents were asked to select 5
      attributes, which were most important for them, from 19 choices of home care
      services, and then to rank 5 attributes in decreasing order of importance to
      determine their priorities, coded from 1 (the first priority) to 5 (the last
      important priority). The degree of satisfaction from a single attribute, whether
      or not the desired attribute was in fact provided, personal data of family
      caregivers, and types of patient's insurance were also included in this study.
      RESULTS: The interviewees were inclined to assign high priority to the ease of
      contacting home care nurses by telephone (73.6%) and the timeliness of obtaining
      needed services in an emergency (63.6%); they were less likely to attach high
      priority to provision of spiritual support (6.3%), respect given by home care
      nurses (5.4%), and acceptance of suggestions (4.5%). Whether a single attribute
      was selected as a top five priority was significantly associated with family
      caregiver's education level, degree of satisfaction with the attribute and
      whether the desired attribute was actually received. CONCLUSIONS: The
      interviewees had different priorities for attributes of home care, and they
      assigned high importance to the attributes less satisfied and received; examples
      are the timeliness of obtaining needed services in an emergency, and the ease of
      contacting home care nurses by telephone.

PMID- 9531739
TI  - Bilioma after laparoscopic cholecystectomy: a case report.
AB  - A 68-year-old female, suffering from gallstones, received a laparoscopic
      cholecystectomy. One year later, a 4x2.5x2 cm mass was noted 3 cm left of the
      umbilicus. Under the impression of intraabdominal tumor, the tumor was excised
      and a bilioma was pathologically proved. Bilioma is an encapsulated bile fluid
      mass, formed after damage of the biliary tree and bile leakage. Only a few cases
      have been reported, but never in the periumbilical area according to review of
      the literature. In addition to sonography, computed tomography, and
      cholescintigraphy, the physicians' alertness is essential for this diagnosis. In
      general, the treatment of choice is percutaneous drainage. But, in this case, the
      bilioma of periumbilical abdominal wall was excised with good prognosis after a
      six-month follow-up.

PMID- 9531740
TI  - Leptomeningeal malignant melanoma arising in neurocutaneous melanocytosis: a case
      report.
AB  - A rare case of histology-proved giant congenital melanocytic nevus (GCMN) with
      symptomatic leptomeningeal melanocytosis is reported. A 26-year-old man had had a
      large patch of pigmented nevus over his back and left arm since birth. He had
      begun to have seizures as well as symptoms and signs of increased intracranial
      pressure about six months before admission. Serial computed tomography of brain
      showed hydrocephalus, diffuse leptomeningeal enhancement and multiple well
      enhanced, rapid-growing nodules on the surface of the cerebellum and left
      parietal lobe. Magnetic resonance imaging (MRI) revealed T1 shortening of
      leptomeninges on precontrast T1 weighted imaging. Skin biopsy was done twice and
      showed intradermal nevus. Biopsy on one of the intracranial nodules revealed
      malignant melanoma arising in the melanocytosis. He died one year after the onset
      of neurologic symptoms. For early diagnosis of neurocutaneous melanocytosis, we
      suggest 1) MRI, and 2) leptomeningeal biopsy in patients with suspected
      leptomeningeal malignant melanoma.

PMID- 9531741
TI  - A large adrenal pseudocyst mimicking malignant intraabdominal tumor: a case
      report.
AB  - An abdominal mass was found in an apparently healthy 66-year-old man during he
      was undergoing a routine physical check-up. Intravenous pyelography showed a huge
      suprarenal cyst displacing the left kidney. Both kidneys had normal renal
      function. The tumor was removed transperitoneally. It contained 1600 ml
      hemorrhagic fluid and had small golden nodules on the inner cystic surface.
      Microscopically, adrenal cortical tissue was present in groups or scattered along
      the cystic wall, which was compatible with the diagnosis of pseudocyst. No lining
      epithelium was present. The differential diagnosis, pathogenesis, management, and
      the general features of adrenal pseudocysts were discussed.

PMID- 9531742
TI  - The painful experience of inappropriate therapy of snake bites: a report of two
      cases.
AB  - Recognizing the exact species of snake and specific antivenin administration are
      the most important modality of treatment for poisonous snake bites. In Taiwan,
      there are six kinds of medically important snakes--two species of Elapidae and
      four species of Viperidae. Two kinds of polyvalent antivenins and one monovalent
      antivenin are available. But for snake bites, questions about the prescription of
      antivenins are still the major problems addressed to the Poison Control Center.
      Improper use of antivenin may delay a patient's recovery from snake poisoning and
      even lead to mortality. Here, two cases of snake bites are presented. Each had
      severe complications and mortality as a result of inappropriate therapy, and the
      most rational management of snake bite in Taiwan is discussed, too.

PMID- 9531743
TI  - [Visualization in inflammatory bowel disease. Video endoscopic technique improves
      the diagnosis].

PMID- 9531744
TI  - [Substantially increased levels in human milk. Unclear about the health hazards
      of brominated flame retardants].

PMID- 9531745
TI  - [Is UV radiation the explanation of geographical distribution? A new theory on
      latitude differences in the occurrence of multiple sclerosis].

PMID- 9531746
TI  - [Medical ethics and personal responsibility. Politically correct excess].

PMID- 9531747
TI  - [No proof of worse care at small birthing clinics].

PMID- 9531748
TI  - [The National Board of Health and Welfare is ready to re-evaluate guidelines on
      Rh-immunization].

PMID- 9531749
TI  - [Why escape to the world of books?].

PMID- 9531751
TI  - [Ethics--competence--information].

PMID- 9531750
TI  - [Same patients must be analysed parallelly when D-dimer methods are compared].

PMID- 9531752
TI  - [New light shed on the enigmatic eosinophilic granulocyte. Both a friend and an
      enemy].
AB  - Eosinophils normally constitute only a few per cent of circulating leucocytes,
      though they are more numerous in tissues vulnerable to attack by environmental
      micro-organisms. Eosinophils can kill invasive parasites, but also possess
      immunoregulatory functions and may be involved, for example, in the connective
      tissue remodelling that occurs in conjunction with inflammation. Although their
      effects may be beneficial to the host, for instance in the event of helminthic
      infestation, they may also cause tissue damage, for example in allergy and
      asthma. Recent years have witnessed manifest advances in our knowledge of these
      fascinating but still enigmatic cells.

PMID- 9531753
TI  - [Leukocyte scintigraphy, endoscopy, airway x-ray. New methods for the diagnosis
      of colitis and Crohn disease].
AB  - In inflammatory bowel disease, the use of various diagnostic techniques to
      visualise the extent and severity of inflammation is of vital importance at the
      onset of disease, in the event of subsequent relapse, and when complications are
      suspected. Medical treatment and surgery can thus be optimised and limited
      operations performed, especially in Crohn's disease. The article consists in a
      summary of published reports from a single centre, representing 10 years'
      experience of three new techniques for assessing inflammatory bowel disease.
      Leucocyte scintigraphy is a non-invasive and well-tolerated method whereby the
      small and large bowels are assessed on the same occasion, and complications such
      as abscesses and possibly fistulas can be visualised. Intraoperative enteroscopy
      yields more accurate information than previous methods for deciding the extent of
      small bowel resections, and often permitting gut to be saved. Air enema
      radiography is a convenient and safe means of obtaining reliable information
      about the presence and depth of ulceration in ulcerative colitis. These methods
      facilitate the care of patients with inflammatory bowel disease, and should be
      made available at centres where such patients are treated.

PMID- 9531754
TI  - [An international project on the targets of medicine. Is it the task of health
      care services to make people happy?].

PMID- 9531755
TI  - ["How a successful scientific career started!"].

PMID- 9531756
TI  - [When evidence based treatment of sinusitis became unscientific].

PMID- 9531757
TI  - [Interference of CK-BB isoenzyme in the determination of CK-MB using the
      immunoinhibition method in patients with pulmonary diseases].
AB  - An increase in serum creatine kinase-MB (CK-MB) isoenzyme is regarded as a
      specific indicator of acute myocardial infarction. We analyzed retrospectively
      the clinical data of 94 patients whose serum creatine kinase MB (CK-MB) was
      measured with immunoinhibition kit which measures all residual CK activity
      following inactivation of M-subunit. There were 21 patients with chronic
      obstructive lung disease (COLD), 17 patients with pneumonia, 17 patients with
      pulmonary tuberculosis (TBC), 16 patients with non-small cell lung cancer
      (NSCLC), 10 patients with small cell lung cancer (SCLC), 8 patients with
      malignancies of other origin (NPL), and 5 patients with chronic heart diseases.
      The results revealed that serum concentrations of CK-MB in SCLC, NSCLC and TBC
      were significantly greater than those in other groups (P < 0.1). Clinical
      examination showed no evidence of myocardial infarction, injury, or tumor
      involvement of the heart. We assumed that those results are due to interference
      of the CK-BB isoenzyme in the immunoinhibition method. So we suggest that in
      clinical practice, markedly elevated levels of CK-MB measured with
      immunoinhibition kit, after the exclusion of the myocardial injury, may point
      toward the existence of a malignancy or TBC of the lungs.

PMID- 9531758
TI  - [Relation between successful treatment of urinary tract inflammation and the
      disappearance of changes in the bladder mucosa in children and adolescents with
      cystoscopically proven cystitis cystica].
AB  - Bladder epithelium nodular changes called cystitis cystica are commonly found in
      children and adolescents suffering from long-term lower urinary tract infection.
      Recurrent urinary infection was found in pediatric patients with urinary tract
      abnormalities as well as in others without it with nearly the same frequency. The
      authors studied 63 pediatric patients with recurrent urinary tract infection and
      cystitis cystica of which 59 (94%) were females. The age of the examined patients
      varied from 1 to 16 years, mean 7.35 years. Thirty five of them (55.5%) had
      diverse anomalies of the urinary tract. Vesicoureteric reflux was demonstrated on
      the cystogram in 41.1% patients. Escherichia coli was found to be the major
      pathogenic organism in the urine. Thirty eight (60.3%) children and adolescents
      were treated medically for months (two years mostly) by reason of prolonged
      recurrent urinary tract infection before nodular changes of the bladder mucosa at
      cystoscopy were detected. Even thirteen (39.7%) of all studied patients were
      treated medically more than five years. In the present study only 47 (74.6%) of
      the observed patients have had an adequate follow-up and might be considered. In
      these cases repeated cystoscopy was performed and the successively sterile urine
      cultures were obtained. Twenty-one (44.3%) patients were medically treated up to
      one year before the urinary tract infection was eradicated and nodular mucosal
      changes disappeared. In 6 (12.8%) patients more than five years were needed to
      achieve this result.

PMID- 9531759
TI  - [Azithromycin in the prevention of Mediterranean spotted fever].
AB  - Antibodies to Rickettsia conorii were detected by the indirect immunofluorescence
      (IFA) assay in 64 (51.6%) out of 124 examinees living in North Dalmatia (Croatia)
      who had a history of recent tick bites during 1994 and 1995. Positive titers of
      IFA antibodies to R. conorii were detected in 12 (31.5%) out of 38 examinees with
      carried out prophylaxis by azithromycin. The usual clinical signs of
      Mediterranean spotted fever were registered in 22 (25.6%) and asymptomatic
      infection in 30 (34.8%) out of 86 examinees without prophylaxis. Clinical signs
      of the disease were not registered in examinees with prophylaxis.

PMID- 9531762
TI  - [Social phobias].
AB  - Social phobia is an anxiety disorder which can be found in general and specific
      subtype in general population from 2.4 to 16%. People who are suffering from
      social phobia don't have opportunities for optimal development and their quality
      of life and work productivity is ruined too. Authors showed definition, diagnosis
      and differential diagnosis, epidemiology, clinical features, quality of life,
      work and social disability of people with social phobia. Biology and therapy of
      social phobia are also presented. This paper is based on findings around the
      world. Authors recommend more attention to social phobia, its specific type which
      is very rare, as much as one in comorbidity because this disorder can make big
      economic costs, especially through work disability, which can be changed by early
      treatment.

PMID- 9531761
TI  - [Optic nerve damage caused by administration of ethambutol].
AB  - We considered the influence of ethambutol therapy for lung TBC on the visual
      function of patients. Cases of toxic optic neuropathy caused by ethambutol
      therapy in patients hospitalized in the Ophthalmic Clinic in Rijeka within 5
      years were presented. Results of the treatment of toxic optic neuropathy caused
      by ethambutol are influenced by risk factors such as: diabetes mellitus, renal
      insufficiency, alcoholism and in our opinion, atherosclerosis and very old age.

PMID- 9531763
TI  - [The effect of trauma surgery on immune system function].
AB  - Severe accidental trauma often causes an immunosuppression accompanied by
      infection and sepsis which may be fatal. Furthermore, elective surgery could also
      cause dysfunction of the immune system. While physiopathological mechanisms of
      such posttraumatic immune system dysfunctions are still not sufficiently
      understood, the scope of research interest is focused particularly on the
      cytokine network and, recently, on the "nonspecific" mediators of oxidative
      stress. In this article some novel findings about the dysfunction of the immune
      system caused by trauma, including surgical injury, are briefly summarized, and
      the involvement of oxidative stress in these changes is emphasized.

PMID- 9531764
TI  - [Inconsistency between clinical practice and the medical terminology in criteria
      for the determination of brain death].
AB  - Transplantation of odd organs such as heart, liver, pancreas and alike is
      possible only through dead donors and cadavers, so the study and research into
      the exact time of death is of paramount importance. It is understood that a
      person is dead when the brain is dead, and from that moment on there is no reason
      to sustain or prolong the life of the remaining living cells, so called
      vegetating living, as governed by the Criteria for brain death. In our country
      the criteria are dated 1982 and the article 5 was subsequently changed in 1991.
      We noticed that some articles of the Criteria were incorrect. The article 4,
      paragraph 9, should be altered because the 3-minute apnea testing is not
      sufficiently long. The laws and various criteria many times lag behind the actual
      practice in everyday life. This also applies to other laws and regulations in
      connection with medical practice, which although is developing fast is kept at
      bay due to slow changes of the laws. This is the case of the criteria regarding
      the brain death which have been adopted without any further thought from the
      criteria of former Yugoslavia. Due to this there have been disagreements
      regarding medical terminology and the laws which govern clinical results. Article
      5 from 1982 and article 5 from 1991 have one thing in common, the EEG. The
      Criteria require EEG although it is not a very reliable method and is not
      required in many other countries. The criteria excluded the necessity of cerebral
      angiography which was shown to have more exact results, although it is more
      complicated. Radioisotope angiography has been excluded as well. The doppler
      ultrasound method has been included in the Criteria, although it is not available
      to many hospitals and, as mentioned previously, could give false positive
      results. The EP have been included in the Criteria as a reliable method, but
      unfortunately not available to many hospitals due to the lack of equipment and
      trained doctors and other medical personnel. Among other difficulties there are
      differences in medical terminology between medical experts, and the awareness of
      different medical terminology between nations, but the original Harward Criteria
      dated 1968 remain the same.

PMID- 9531765
TI  - [Vancomycin-resistant enterococci].

PMID- 9531768
TI  - Methods of molecular genetics in microbiology--step into the future.

PMID- 9531769
TI  - [Coronary score in patients with low ejection fraction after myocardial infarct].
AB  - INTRODUCTION: The most frequent cause of heart failure is ischemic heart disease
      (1). This paper was aimed at comparing the coronary score of patients with low
      ejection fraction whose ejection fraction was not significantly changed after
      sustained myocardial infarction. MATERIAL AND METHODS: The study involved
      patients after sustained myocardial infarction treated at the Institute of
      Cardiovascular Diseases in Sremska Kamenica. Total coronary score and score of
      each individual coronary artery were emphasized. RESULTS: The investigation study
      comprised 56 patients aged 33-83 years of various occupations. Patients were
      divided into two groups: the first--A group consisted of 28 (50%) patients with
      ejection fraction 35% or lower; the second--B group also consisted of 28 (50%)
      patients with ejection fraction higher that 35%. Table 1. shows the dominant
      coronary artery in investigated groups of patients. Table 2. shows values of
      total and scores of each coronary artery. The right coronary artery was dominant
      in 75% of patients from the A group and in 82.1% of patients from the B group. A
      significantly higher individual score of coronary arteries, as well as the total
      score, was established in the group of patients with low ejection fraction, and
      especially the score of the anterior descendent artery which is almost twice
      higher in regard to the second group of examined patients. Table 3. describes the
      analyzed score in male and female patients. DISCUSSION: Patients with low
      ejection fraction after sustained myocardial infarction have more changes of
      coronary arteries than patients with better ejection fraction. The total score,
      score of the right coronary artery (ACD), circumflex artery (RCX) and especially
      anterior descendent artery (LAD) are significantly higher in patients with
      ejection fraction lower than 35%. There are no differences in the dominant
      coronary artery in investigated patients. In both investigated groups women had a
      smaller score of ACD and RCX and a higher score of LAD, but the difference is not
      significant. In regard to total score there were no differences in men and women.
      Numerous investigations also point to the fact that patients with lower ejection
      fraction and ischemic heart disease have more changes on coronary artery than
      patients with better ejection fraction. CONCLUSION: 1. Patients with low ejection
      fraction after sustained myocardial infarction have a higher total score and
      scores of ACD. LAD and RCX. 2. There are no differences in coronary score of men
      and women within the same investigated groups. 3. There are no differences in
      dominant coronary artery in investigated groups of patients.

PMID- 9531770
TI  - Effects of cadA gene on cell division phenotype.
AB  - Studying cell division regulatory mechanisms in Escherichia coli an important
      role of cad operon was discovered. The cadA gene is part of the cad operon. The
      promotor of cad operon (pBA) regulates two genes, cadB (the first gene in the cad
      operon) and cadA (the second one). The cadB encodes the lysine-cadaverine
      antiporter. The cadA gene encodes enzyme lysine decarboxylase that turns lysine
      into cadaverine and carbon dioxide. The expression of cadA is activated by
      several different environmental parameters, such as low pH, low oxygen, and
      excess lysine. Regulation of any of these parameters depends on the presence of
      cadC gene, encoding the regulator of the operon. It is located upstream of cad
      operon. The aim of this study is to investigate if the effect upon the cell
      division rate was caused by the induction of cadA. Specific aims were to obtain
      structural gene of cadA and construct a plasmid (pAM1) that contains cadA under
      the control of the arabinose inducibile promoter pARA, and complement the cell
      division phenotype of a cadA mutant by providing cadA on the inducibile plasmid.
      Activation of the pAM1 with 0.05% arabinose reduced the cell division rate that
      confirms the inhibitory effect of the pAM1.

PMID- 9531771
TI  - [Current knowledge on cryopreservation of spermatozoa, ovum cells and zygotes].
AB  - CELL INJURIES DURING FREEZING AND THAWING: The aim of various cryopreservation
      procedures is to minimize cell injuries during the freeze-thaw cycle
      (cryoinjuries). Generally, the cell damage during freezing and thawing procedures
      may be the results of: (a) extensive cellular dehydration (solution effect)
      and/or (b) intracellular ice crystallization/recrystallization (mechanical cell
      damage). Two independent mechanisms are involved. They can act simultaneously,
      leading to cytolysis. The first one is expressed primarily during low rate
      freezing, and the second one during rapid freezing. Thus, determination and use
      of the optimal cooling velocity, specific for each type of isolated cells, should
      be considered. Finally, a higher degree of cell destruction has been documented
      when the transition period from liquid to solid phase (release of the fusion
      heat) is prolonged. CRYOPROTECTIVE AGENTS: For successful cell cryopreservation,
      cryoprotectants are needed. They decrease the osmotic gradient and the vapor
      pressure difference between the intra- and extracellular area. Adequate choice of
      the most suitable type and concentration of cryoprotective agent is important for
      the required cell recovery after thawing. There are several well known protocols
      for obtaining cryopreservation of isolated cells using different cryoprotectants.
      Glycerol, dimethyl sulfoxide (DMSO) and propanediol sucrose are commonly used as
      cryoprotectants, though in different concentrations. Glycerol, a trihydric
      alcohol, is a clear, colorless fluid. Pharmacologically, it is relatively inert.
      DMSO is a colorless liquid with a sulphur-like smell and has several medical
      uses. It is highly polar and dissolves many water- and lipid-soluble substances.
      DMSO given intravenously may cause nausea, vomiting, local vasospasm and an
      objectionable garlic-like odor and taste. HUMAN SPERM, OVA AND EMBRYOS
      CRYOPRESERVATION: Despite the fact that cryopreservation procedures of
      spermatozoa, ova and embryos are already in routine clinical use, some questions
      related to the optimal cooling velocity during controlled-rate freezing and the
      choice of the most effective, either penetrating (glycerol, dimethyl sulfoxide)
      and/or non-penetrating (hydroxyethyl starch) cryoprotective agent at the
      appropriate concentration are not resolved.

PMID- 9531772
TI  - [Quality of life and its measurement].
AB  - INTRODUCTION: At present quality of life has a significant place within health
      care and scientific research work. This interest is stimulated by the fact that
      people want to live, not just to survive. The problem of quality of life in
      persons whose lives could not be preserved, opens discussions concerning
      artificial subsistence of life, euthanasia etc. This is not a new topic. What is
      new is development of official ways to measure quality of life and their routine
      application. CONCEPT OF QUALITY OF LIFE: In general, quality of life can be
      defined as the level of well-being. It cannot be identified with health, but
      probably primarily with ability to conduct an economically and socially
      productive life. Quality of life refers to physical, psychological and social
      domains of health, being influenced by one's experience, beliefs, expectations
      and perceptions. There is no consensus concerning the concept of quality of life
      and according to the same authors it includes functional ability, level and
      quality of social interactions, physical welfare, somatic sensations and life
      satisfaction. Generally speaking concepts include numerous dimensions and
      possibilities occurring during life, to death itself (Table 1). Although
      objective dimension of health is important in assessment of patient's health,
      subjective estimation and expectations make, what is found to be an objective
      situation, experienced quality of life (Graph. 1). MEASURING QUALITY OF LIFE: The
      most difficult task is to present various segments of health into quantitative
      values. All data can be measured at nominal, ordinal, interval or ratio scales.
      The nominal scale uses numbers and other symbols in classification of
      characteristics. Categories cannot be classified according to volume and are
      mutually exclusive. Ordinal scales are used when measuring a limited number of
      categories classified according to quality. Interval scales measure an unlimited
      number of categories with equal intervals and they are without a real zero point.
      Ratio scales have all the characteristics of interval scales, but they have real
      zero points. CHOICE OF MEASURING INSTRUMENTS: There are different instruments to
      assess quality of life such as generic instruments, battery scales and modular
      instruments index methods and instruments. The measuring instruments should be
      reliable, valid, responsive and sensitive. QUALITY OF LIFE EVALUATION: Three
      design studies are most frequently used: cross-sectional or nonrandomized
      longitudinal studies, randomized studies of clinical interventions and cost
      effective and cost benefit analyses.

PMID- 9531773
TI  - [Subjective syndrome after head injury].
AB  - DEFINITION AND CLASSIFICATION PROBLEMS: Post-traumatic or post-commotion syndrome
      is one of the most controversial entities in studying consequences of
      craniocerebral trauma. Part of this problem arises from impossibility of adequate
      translation of the term brain concussion. Post-concussion syndrome is a broader
      concept than post-commotion and includes, if not a whole, than part of the post
      contusion syndrome. There are also some other terms in the literature: post
      traumatic syndrome, post head injury syndrome, post head injury syndrome or
      symptoms and the old term post-traumatic encephalopathy. Terminological
      imprecisions have not been solved yet, but the notion itself is determined by
      relative standard symptoms often associated with closed craniocerebral trauma,
      but without precise connection with the severity of the trauma. In the
      classification of mental disorders and behavior disorders, this syndrome is coded
      as FO7.2. ETIOLOGY: In regard to the etiology of this syndrome some authors speak
      in favor of psychogenic and some of organic etiology, while Levin considers
      symptoms of post-commotion syndrome to start as organic and persist as psychic.
      Wechsler classified subjective disorders after head injuries into 4 categories:
      simulation, traumatic hysteria, traumatic encephalopathy and traumatic neurosis.
      The author does not deal with the origin of symptoms, whereas the classification
      itself suggests priority of psychic to organic factors (11). Those who speak in
      favor of organic etiology, think that axon damage and neuron damage are organic
      substrate in mild brain injuries, while fibrous degenerations of the cerebral
      hemisphere and brain stem are the organic base in severe traumas. On the other
      hand, many scientists primarily point to psychic moments, especially to
      importance of aggravation and simulation as well as compensation or rental
      neurosis in persistent post-traumatic syndrome. Most scientists agree that
      personality characteristics influence the development of post-traumatic syndrome
      and can predispose aggravation and simulation, whereas these symptoms more often
      occur in neurotic persons. The latest investigations reveal that classification
      in regard to etiologic factors--organic and psychogenic--is an anachronism. Long
      and Novac state that 80% of persons with cerebral trauma spontaneously speak
      about symptoms of the post-traumatic syndrome, while by targeted evaluation the
      percentage rises to 90%, so that they think that universality of symptoms points
      to their common origin. CONCLUSION: If the post-traumatic syndrome is though of
      as a line with organic dementia at one end and traumatic neuroses at the other,
      then this syndrome can be placed at different positions. Some authors put it
      close to the neurotic syndrome or regard it to be the neurotic syndrome itself,
      while others, mostly due to homogenity of the clinical picture, believe that this
      syndrome has an organic cause.

PMID- 9531774
TI  - [Genital herpes with special emphasis on perinatal herpes simplex virus
      infection].
AB  - INTRODUCTION: The incidence of genital herpes is increasing worldwide and at
      present herpes simplex virus type 2 is the most common cause of genital
      ulceration all over the world. CLASSIFICATION: The International Herpes
      Management Forum (IHMF) was established in 1993, suggesting a new classification
      of genital herpes: primary genital herpes, non-primary genital herpes, recurrent
      genital herpes, first episode genital herpes, atypical genital herpes and
      asymptomatic HSV (herpes simplex virus) infection. DIAGNOSIS: Clinical diagnosis
      of genital herpes should be confirmed by laboratory techniques, whereas a
      positive HSV culture is the best test for confirming the clinical diagnosis.
      Serological testing, including Western blot assay, is not the method of choice
      for diagnosis genital herpes. THERAPY: Management of patients with genital herpes
      must include various antiviral drugs (acyclovir, valacyclovir, famiclovir), but
      also must take into consideration the patients' clinical and emotional issues.
      Patients with few recurrences are best managed with episodic antiviral therapy,
      but those with more frequent recurrences may find a long term suppressive therapy
      more beneficial. Herpes simplex virus is acquired during labor in about 90% of
      neonatal herpes virus cases with direct contact with infected maternal genital
      secretions, in 5% of cases in utero (ascending infection or transplacentary) and
      in another 5% of cases HSV is acquired post partum. Herpes simplex virus
      infection includes skin infection, eye and mouth manifestations, CNS diseases and
      disseminated disease with multiorgan involvement. CONCLUSION: In order to reduce
      the risk of HSV transmission to the infant IHMF has suggested management of
      pregnant women with primary genital herpes: delivery by Caesarean section between
      34th week and term. Acyclovir treatment may reduce the viral load at delivery,
      but before this can generally be recommended, more data are still required.

PMID- 9531775
TI  - [Pathogenesis and methods of treatment of otogenic brain abscess].
AB  - Otitis media, acute or chronic, is a potentially dangerous disease which may lead
      to fatal complications. Meningitis is the most common intracranial complication,
      followed by otogenic brain abscesses while lateral sinus thrombosis is fairly
      uncommon. Mortality from otogenic brain abscesses remains relatively high. The
      aim of the study was to investigate mechanisms of development, diagnostic methods
      and treatment of these complications of otogenic brain abscesses. MATERIAL AND
      METHODS: The retrospective study covered 42 patients with otogenic brain abscess
      (28 cerebral and 14 cerebellar) treated from 1973 to 1995 at the ENT and
      Neurosurgical Hospital in Belgrade. Medical records of the studied patients were
      analyzed for the occurrence of the disease, diagnosis and mode of therapy.
      Special care was dedicated to type of otitis, surgical findings, diagnostic
      methods, mode of therapy and therapy outcome. RESULTS: In the period of 23 (1973
      1995) 114 patients with otogenic intracranial complications were treated at the
      Clinic of Otorhinolaryngology and Maxillofacial Surgery. Meningitis was the most
      common complication in this series, followed by cerebral abscess, lateral sinus
      thrombosis, cerebellar abscess, while extradural abscesses were rare, and
      subdural occurred only exceptionally (Table 1). In somewhat more than half of the
      patients (55%) one intracranial complication was present, While in 54% two or
      more intracranial complications were recorded (Table 2). Otogenic brain abscesses
      are usually associated with meningitis. Meningitis was present in 20 patients
      with cerebral abscess (71%), and in 5 (33%) patients with cerebellar abscess.
      Meningitis and lateral sinus thrombosis were more commonly associated with
      cerebellar abscess (41%), and less with cerebral abscess (10%). In our group of
      patients otogenic brain abscesses were most common in the third decade of life,
      than in the second, while the frequency of the complication fell significantly in
      older age groups (Figure 1). Headache (92%). fever (91%), vomiting (68%) were the
      most common symptoms, while photophobia and vertigo were less common (38% and
      30%, respectively). Active chronic otitis with cholesteatoma was most commonly
      present in patients with otogenic brain abscess, only somewhat more common in
      patients with cerebral abscess (84%), than in those with cerebellar abscess
      (80%). Neurological examination of 28 patients with cerebral abscess evidenced
      the abscess in 11, while in 15 the examination suggested meningitis. (Table 3).
      The diagnosis of abscess was most commonly established by computerized
      tomography. It revealed cerebral abscess in 18 out of 28 patients, and cerebellar
      abscess in 10 out of 12 patients. (Table 3). Radical trepanation of the temporal
      bone was performed in all our patients, while in nine patients revision was
      required after the surgery, since the initial operation was not sufficiently
      radical. (Table 4). Out of 28 patients with cerebral abscess 5 (18%) died while 3
      (29%) patients died out of 14 patients with cerebellar abscess (Table 4).
      DISCUSSION: Otogenic brain abscesses imply accumulation of pus in the cerebrum or
      cerebellum developing after encephalitis, caused by pyogenic microorganisms
      originating from inflammatory process in the middle ear cavity. This is a severe
      otogenic complication with high mortality. Even with modern therapeutic
      alternatives, mortality remained high, about 40% (7). According to the data
      reported by several authors introduction of antibiotic therapy resulted in
      drastic fall of associated mortality. The annual risk of otogenic abscess of the
      brain is 1 per 1000 adults with active chronic otitis. The incidence of abscess
      is significantly higher in a certain age groups, i.e. 1 per 200 between the ages
      of 20 and 40 (3). The diagnosis of brain abscess established clinically is not
      quite reliable. The disease is usually associated with severe meningitis, so that
      neurological examination usually detects only signs of meningi

PMID- 9531776
TI  - [Peripheral neurologic complications after carotid surgery].
AB  - INTRODUCTION: In recent years, with development of carotid surgery and
      significant decrease of central neurological complications, more and more
      attention has been paid to the occurrence of peripheral neurological
      complications. Most frequent neurological lesions are as follows: auricularis
      magnus nerve, hypoglossal nerve, vagal nerve, inf. laryngeal nerve, sup.
      laryngeal nerve, glossopharyngeal nerve and spinal nerve. MATERIAL AND METHODS:
      In the period from May 1995 to January 1997, 97 patients underwent surgery
      because of carotid arteries lesions. Bilateral lesion of carotid arteries was
      treated in 27 patients. Standardized surgical procedures were performed while
      neurological examinations were performed postoperatively to check for possible
      peripheral neurological deficit. RESULTS: Cerebrovascular insult was the cause of
      death in one patient (1.2%). Transitory ischemic attack also occurred in one
      patient (1.2%). Peripheral nerve lesions were observed in 13 patients that is in
      11.3% of cases; auricularis magnus nerve lesion in 9 patients (8.3%); sup.
      laryngeal nerve lesion in 3 patients (2.8%); mandibular branch of the facial
      nerve lesion in one patient (0.9%). DISCUSSION: The global incidence of
      postoperative peripheral neurological complications after carotid surgery was
      11.3% cases, while according to the literature data it is from 10.5% to 13%. The
      most frequent are the lesions of auricularis magnus nerve and sup. laryngeal
      nerve. CONCLUSION: The incidence of peripheral neurological complications is
      higher than it is thought to be. Majority of these lesions are with transitory
      effect. Good knowledge of the precise surgical technique is a prerequisite to
      decrease the rate of these complications.

PMID- 9531777
TI  - [Clinico-histologic characteristics of spinocellular carcinoma of the skin].
AB  - INTRODUCTION: Authors present clinical-histological characteristics of squamous
      cell carcinomas of the skin in patients treated at the Clinic of Infectious and
      Dermato-Venereology Diseases in Novi Sad in the period from 1989 to 1995.
      MATERIAL AND METHODS: The examined group comprised 26 cases (2.32%) with
      histologically verified squamous cell carcinomas of the skin out of 1119
      nonmelanomatous epithelial skin tumors, clinically examined by dermatologists and
      treated by x-ray surface therapy. All patients with SCC were clinically examined
      by dermatologists at the Clinic of Dermatology and Venereology in Novi Sad, while
      histological examinations were performed by pathologists of the department of
      Pathology and Histology of the Faculty of Medicine in Novi Sad. Tumor biopsy
      specimens were obtained by shave biopsy, saucer biopsy and punch biopsy. All the
      biopsy specimens wee histologically examined and verified with standard methods
      with haematoxyllineosin-staining. RESULTS: In the group of examined patients most
      were with SCC--that is exophytic tumor of the skin in 16 cases (61.54%).
      Histological examination revealed: squamous cell carcinoma of the skin in 9 cases
      (56.25%), keratotic squamous cell carcinoma in 5 cases (31.25%) and invasive
      squamous cell carcinoma in 2 cases (12.50%). In the examined group there were
      also 9 cases of SCC (36.41%) with clinical forms of endophytic tumor of the skin.
      By histological examination the following tumors were diagnosed: Morbus Bowen in
      3 cases (incipient squamous cell carcinoma of the skin) (33.33%); squamous cell
      carcinoma of the skin in 5 cases (55.56%) and keratotic squa- mous cell carcinoma
      in 1 case (11.11%). In one case SCC with clinical features like keratoacanthoma
      was found (3.85%), while by histological examination keratotic squamous cell
      carcinoma of the skin was diagnosed. DISCUSSION: In regard to the biopsy
      technique, SCC of the skin was diagnosed mostly as spinocellular carcinoma of the
      skin in 14 cases (53.85%) without a more precise description of the degree of
      tumor cells degeneration as well as tumor edge characteristics and type of
      histological type of tumor. Keratotic squamous cell carcinoma was found in 7
      cases (26.92%); it is a tumor of mature structure (1-2 Broders' grade of clinical
      stage of tumors), but also without a detailed description of the tumor edge and
      type of histological type of tumor. Invasive squamous cell carcinoma was found in
      2 cases (7.96%) and it reveals a SCC of the skin with deep infiltration into the
      dermis and hypodermis, sometimes involving the neighboring tissue (cartilage
      tissue, bone, muscle tissue and so on). This histological form of SCC had 3-4
      Broders' grade of clinical stage of tumors. CONCLUSION: Authors of the paper
      conclude that histological examinations of SCC of the skin are necessary meaning
      detailed analysis: degree of differentiation of tumor cells by Broders'
      examination, examination of tumor edges and histological types of tumor. The
      incisional biopsy of tumor lesions had only been used to confirm clinical
      diagnosis in order to perform x-ray therapy, but it could not meet necessary
      criteria the excisional biopsy could in regard to evaluate tumor edges and
      histological type of the tumor.

PMID- 9531778
TI  - [Adverse effects and recovery after total intravenous anesthesia in children].
AB  - INTRODUCTION: Propofol has proven to be a reliable anaesthetic that can be used
      for both induction and maintenance purposes in most common surgical procedures,
      either in standard anaesthetic practice or as part of total intravenous
      anaesthesia (TIVA). MATERIAL AND METHODS: Twenty healthy (ASAI) paediatric
      patients scheduled for elective minor abdominal or urology surgery were studied.
      Patients aged 7-16 years, weighing 25-64 kg, were premedicated with midazolam
      0.1mg/kg and atropine 0.01mg/kg intramuscularly, 30 minutes before surgery.
      Induction dose of propofol for all patients was 2.5 mg/kg. Anaesthesia was
      maintained with an infusion of propofol 10 to 15 mg/kg/h. Fentanyl was injected 1
      2 micrograms/kg 1 minute before the start of the infusion of propofol, just
      before the surgery and during the surgery if necessary. Pulse, blood pressure,
      respiratory rate, tidal volume, ETCO2, and O2 saturation were continuously
      recorded before, during and after the anaesthesia. Recovery scores were assessed
      with the Steward scoring system 3, 5, 15, 30, after the end of anaesthetic
      infusion. Blood was sampled 2 and 15 minutes after the induction, 5, 15 and 30
      minutes after the end of propofol infusion. RESULTS: There were no significant
      differences in age, weight, sort and length of the operations. After the
      induction spontaneous movements were registered in 35% of the patients, apnea in
      25% and decrease in blood pressure in all patients. Maintenance was generally
      uneventful and there were no excitatory or other adverse effects. Blood
      concentration of propofol was followed during the anaesthesia and recovery
      period. Blood propofol concentration at which responses to surgery were not
      present were from 3.4 micrograms/ml to 4.5 micrograms/ml. Recovery was rapid and
      complete. All patients reached maximum value of Steward scoring system within the
      first 15 minutes. In the moment when patients open to command (7.2 +/- 3.2 min)
      average blood concentration was 1.9 micrograms/ml and when they were orientated
      (13.1 +/- 2.1 min) 1.3 micrograms/ml. Postoperative nausea and vomiting were not
      registered. DISCUSSION: This study shows that propofol provides satisfactory,
      stabile anaesthesia for children with rapid and complete recovery. Children may
      need larger doses of propofol for induction and maintenance of anaesthesia.
      Results from literature suggest that propofol is metabolised faster in children
      than in adults (9). The incidence of side effects was low. Large vein of the
      forearm or antecubital fossa were used for injection of propofol and there was no
      pain during administration the drug. Induction dose was given slowly (over 40
      seconds) and apnea was relatively rare (25%). Decreases in arterial pressures
      from baseline levels are known to occur with propofol but in this study it was
      less than in others. We find a relatively high incidence of spontaneous movements
      during induction (35%). Nausea and vomiting were not recorded. A continuous
      infusion of propofol, as described here, effectively produced stable anaesthesia
      without use of inhalation agents. It must be remembered that propofol possesses
      only hypnotic properties and additional analgesia is necessary, fentanyl is a
      satisfactory agent in this respect. We found that average blood propofol levels
      of 3.5 +/- 0.9 micrograms/ml were necessary to prevent autonomic responses during
      this sort of surgery. Suggested hypnotic blood levels of propofol in literature
      are from 2.5 to 6 micrograms/ml (5). The usual endpoints of anaesthesia (eye
      opening and orientation) have been measured by several authors and found to occur
      at concentrations of the ranges of 1.0 to 2.9 micrograms/ml and 0.6 to 1.8 g/ml,
      respectively. CONCLUSION: Due to greater ease of control in regard to anesthetic
      depth and more rapid recovery, propofol is superior to other intravenous
      hypnotics for maintenance of anaesthesia.

PMID- 9531779
TI  - [Asymptomatic myocardial ischemia before and after surgical revascularization in
      patients with multivessel occlusive coronary disease].
AB  - INTRODUCTION: The objective of this study was to examine the occurrence of
      asymptomatic myocardial ischemia prior to and after myocardial revascularization
      in patients with multivessel occlusive coronary disease. Asymptomatic ischemia
      can be described as real ischemia without anginal pain or other ischemic symptoms
      in patients with coronary disease or coronary artery spasm. Our study examined
      silent ischemia after myocardial revascularization. Early detection of silent
      ischemia is important for prevention of cardiac incidents. MATERIAL AND METHODS:
      We have examined patients with multivessel coronary disease with occurrence of
      continued preoperative silent ischemia. All patients have undergone ECG
      examination, exercise stress test and Holter-monitoring prior to and after
      myocardial revascularization. RESULTS: The investigation comprised 27 patients
      and their average age was 54.5 years. All patients with silent ischemia had a
      multivessel occlusive coronary disease and have undergone myocardial
      revascularization managed with triple or quadruple aortocoronary bypass surgery.
      Exercise stress test was performed postoperatively in elder patients, as well as
      ECG and Holter-monitoring. Silent ischemia was established in 21.6% of patients,
      while in 87.5% untreated diabetes mellitus was diagnosed. Silent ischemia most
      often occurred in the early morning hours and it was frequently associated with
      heart rhythm disturbances (VES) whereas these rhythm disturbances depended on the
      length of the ischemic episode. Intermittent 2nd degree atrioventricular block
      was found in one patient. CONCLUSION: Silent myocardial ischemia occurred in 21%
      of patients after myocardial revascularization. It is most often detected in the
      early morning hours and is associated with ventricular rhythm disorders. Silent
      ischemia is easily detected by simple examination procedures providing adequate
      therapy and prevention of cardiac incidents.

PMID- 9531780
TI  - [Lymphoma of the parotid salivary gland].
AB  - INTRODUCTION: Lymphomas appear mostly in lymph nodes and parenchymal organs such
      as liver and spleen, while other localizations are less frequent. They are
      classified as Hodgkin and non-Hodgkin types, and these two are divided into
      subtypes, according to cell morphology and the characteristics of concurrent
      elements. Parotid salivary gland lymphomas are rare primary tumours of this
      region, although 80% of all salivary gland lymphomas, appear in parotid. They
      originate from intraparotid or periparotid lymph nodes, or from lymphoid elements
      of other pathological states in the gland such as sialadenitis, cysts with the
      presence of lymphoid tissue, parenchymal neoplasms with lymphoid component
      present and autoimmune illnesses, esp. Sjogren syndrome. Many authors (2-15) who
      have issued publications on this topic in foreign professional literature in the
      past ten years, agree that the primary localization of lymphomas in parotid
      salivary gland is very rare, although in recent decades more frequent than
      earlier (5). In majority of cases they appear on one side, although there are
      very rare cases of described parotid salivary glands on both sides. The illness
      most often starts as painless, soft knob in the region of parotid salivary gland.
      Other discomforts are very rare, and mostly appear as a feeling of pressure and
      mild painful sensations in the region of the change. In case of facial nerve
      paresis and/or strong pains, as well as adenopathy, there is a justified
      suspicion of carcinoma (20). The treatment is surgical. The method chosen is
      parotidectomy. According to histological type and clinical stadium, it includes
      radiotherapy or polychemotherapy. The prognosis depends on histological type of
      tumour, that is clinical stadium, and shows no specific characteristics compared
      with other forms of disease appearing outside parotid salivary gland. CASE
      DESCRIPTION: The patient aged 66 was admitted to the ward with a tumefaction in
      the right parotid region. Family case history: negative. Personal case history
      excerpt: over 20 years of rheumatism, chronic bronchitis and hypertension.
      Present discomfort: tumefaction in the right parotid region, noticed about a year
      and a half earlier. The tumefaction was about 3 cm in diameter, painless to
      palpation, rubbery and smooth. She came to the Otolaryngology ward on May 31,
      1995, when it was established that she had a tumour of the right parotid region
      and chronic otitis media on the left side. She was admitted on August 7, 1995.
      Local test results: the right parotid region contained a tumor of irregular round
      shape, about 6 cm in diameter, soft and painless to palpation, with smooth
      surface, the skin over the tumor was hyperaemic and sporadically livid. ORL
      status excerpt: subtotal reniform perforation of the left tympanic membrane
      enclosing all parts except the attic, with slight transparent secretion. Enlarged
      lymph nodes were not palpable. On August 10, 1995, under general endotracheal
      anaesthesia, a pre-operative aspiration of tumor was performed in three
      positions. The obtained substance contained blood, after which it was decided to
      perform an excision biopsy, which was done in the lower portion of the tumor.
      Histopathological analysis did not give a clearly defined character of tumor, so
      that hospitalisation was indicated and scheduled for further treatment. On the
      second admission on October 10, 1995, general condition and local results remain
      unchanged. On October 12, 1995, total parotidectomy was performed under general
      endotracheal anaesthesia. A tumor of about 5 cm in diameter and the removed
      salivary gland were sent to histopathological tests. The post-operative course
      was normal, the function of the facial nerve was preserved. Histopathological
      results: well-differentiated malignant lymphocyte lymphoma. The patient was sent
      to polychemotherapy on Cyclophosphamide Oncovin Pronisin (COP) protocol. One year
      after the surgery, the local findings are regular. (ABSTRACT TRUNCATED)

PMID- 9531781
TI  - [Placenta percreta--surgical treatment and personal experience].
AB  - This is a case report of a female patient with placenta percreta in whom
      pregnancy was terminated in the XXVII gestational week. The disease was not
      diagnosed during pregnancy which had a normal course; the suspicion appeared
      during the third stage of the delivery period and it was confirmed during the
      operation and subsequent histopathological finding. As profuse bleeding occurred,
      urgent laparotomy with hysterectomy and unilateral adnexectomy were performed.
      Thirteen hours after the delivery the infant died.

PMID- 9531782
TI  - [Hospitals and some outstanding physicians of Pancevo].
AB  - This paper is a retrospection of hospitals and some outstanding physicians who
      lived in Pancevo, written in the honor of 50th anniversary of "Medical Review".
      Hospital bed capacity and the process of building hospitals have been: described
      briefly. Fire and wars have destroyed a lot of written evidence important for
      Pancevo health services. Nevertheless, the preserved sources let us read about
      facts that have already or will soon become part of the history of medicine.
      Apart from this, the paper also contains important details from the life and work
      of Konstantin Peicic (1802-1882), a famous physician, writer of the first Serbian
      original medical book "De pauperum aegrorum" (About Treating the Sick and Poor)
      and many other medical and fine literature works. He had worked in Pancevo for
      more than 30 years, but after he had retired, he moved to Budapest to become the
      manager of the Tekelianum in 1874. He spoke Latin, Hungarian, French, Italian,
      German and of course Serbian language. The paper also gives data on some other
      physicians: Ljubomir Nenadovic a dentist and a writer, Jovan Jovanovic-Zmaj, a
      physician and a great Serbian poet and a founder of the journal "Ziza" and
      assistant of the journal "Pancevac" founded in 1869, and so on. The above
      mentioned physicians had lived and worked in Pancevo since the first medical
      institution "Kontumac" was built in 1726, but then others were built too: the
      first civil hospital in 1803 and the first army hospital in 1830. Modern
      departments were built in 1965, whereas the Children's Department for Internal
      Diseases and the Department for Internal Diseases were built in 1974. This
      retrospection tried to present the history of Pancevo as well as great people
      from our past who worked there to our readers. They were great physicians,
      educators and gifted writers.

PMID- 9531783
TI  - [Helicobacter pylori--thoughts and dilemmas].

PMID- 9531784
TI  - Surgical practice in the prehistoric Aegean.

PMID- 9531785
TI  - [Physicians of the court of Cesar: functions and therapeutic methods].

PMID- 9531786
TI  - [Objectivity and rhetoric. Karl August Wunderlich (1815-1877) and clinical
      thermometry].

PMID- 9531787
TI  - [Cheated of his life's work: Walter Guttman (1873-1941) and his medical
      terminology. Or: of the mistakes and errors of German biblio- and historiography
      and the sequelae of uncritical compiling in the computer age].

PMID- 9531788
TI  - [Conflict of interest].

PMID- 9531791
TI  - [Attack of head lice (pediculosis capitis). Diagnosis, prevention and control].

PMID- 9531789
TI  - [Treatment of migraine attacks and migraine prophylaxis: recommendations of the
      German Migraine and Headache Society].

PMID- 9531790
TI  - [News in cardiology. Reports from the 19th Congress of the European Society for
      Cardiology in Stockholm and from the 70th anniversary of the American Heart
      Association in Orlando].

PMID- 9531792
TI  - [New HIV treatment guidelines].

PMID- 9531793
TI  - [Der Ophthalmologe--listed in Current Contents].

PMID- 9531794
TI  - [Comparative laser tyndallometry and fluorophotometry in anterior and posterior
      uveitis].
AB  - Recent studies have sought to quantify aqueous flare by laser flare measurement.
      An increase in aqueous flare caused by a rise of protein concentration was
      frequently found both in anterior and posterior segment disease. This has been
      interpreted as a break-down of the blood--aqueous barrier (BAB). By measuring the
      diffusion coefficient of the BAB compared to the aqueous flare value in patients
      with anterior and posterior uveitis, the extent to which the increase in flare
      value was related to a possible break down of the BAB was examined. PATIENTS:
      Thirty-nine normal eyes (23-78 years; 41.6 +/- 18.6), 18 eyes with anterior
      uveitis (iritis, iridocyclitis; 18-57 years; 35.2 +/- 12.4) and 29 eyes with
      posterior uveitis (chorioretinitis or retinochorioditis; 18-51 years; 31.7 +/-
      10.5). The diffusion coefficient P(a) of the BAB was measured
      fluorophotometrically, while the flare value was quantified by laser flare
      measurement. RESULTS: Flare values (1/ms) were found to be significantly
      increased (p < 0.001) compared to normal eyes (4.6 +/- 1.7) both in anterior
      uveitis (20.9 +/- 8.5) and in posterior uveitis (17.4 +/- 8.3) but did not
      significantly differ between them (p = 0.43). The diffusion coefficient P(a) (10(
      3)/min) of the BAB was not significantly different (p > 0.05) between normal eyes
      (0.5 +/- 0.2) and eyes with posterior uveitis (0.9 +/- 0.7), whereas it was
      significantly increased (p < 0.001) in anterior uveitis (6.5 +/- 5.4) compared to
      the other groups. CONCLUSIONS: (1) In posterior uveitis, an increased flare value
      is not necessarily correlated with a breakdown of the BAB; proteins may enter the
      aqueous from posterior. (2) Assessing the function of the BAB in posterior
      segment disease using laser measurement should be carried out with caution; if
      possible, permeability measurements of the BAB should be undertaken separately.

PMID- 9531795
TI  - [Immunohistologic studies of the vitreous humor].
AB  - BACKGROUND: Immunohistological staining of the vitreous is difficult because of
      its high water content. We present a method for immunohistological staining of
      celloidin-embedded eyes. Results from diabetic and non-diabetic eyes are
      demonstrated. METHOD: Diabetic and non-diabetic eyes were firstly immersed in
      formol and then slowly dehydrated using rising concentrations of glycerine (sink
      method). Subsequently, the whole globe was embedded in celloidin and cut into 200
      micron sections. Control areas of interest were dissected from the 200 microns
      sections under a lightmicroscope. These specimens were then embedded in paraffin
      and cut into 7-micron sections. The 7-micron sections were immunohistochemically
      stained for type I-collagen, type IV-collagen, fibronectin and laminin. RESULTS:
      This method makes immunohistochemical staining of the vitreous possible. Type IV
      collagen, laminin and fibronection were found at higher concentrations in
      diabetic eyes than in normal eyes. Type I collagen was detected in neither
      diabetic nor in normal eyes. CONCLUSIONS: Our method of examination allows
      immunohistological staining of the vitreous in its place of origin. Although our
      method is time consuming, it has some advantages over biochemical analysis: Even
      minimal changes and their exact distribution can be detected. Our first results
      show that the vitreous is built up inhomogeneously and that pathological
      influence can cause structural changes.

PMID- 9531796
TI  - [North Carolina macular dystrophy. Hereditary macular disease with good
      functional prognosis].
AB  - BACKGROUND: North Carolina macular dystrophy (NCMD) is a rare autosomal dominant
      maculopathy with highly variable expressivity. Genetic analysis of an American
      family consisting of 247 members out of which 96 were affected with NCMD allowed
      chromosomal assignment of the NCMD locus to 6q14-q16.2. Few families with NCMD
      are known in Europe, one of these is living in Germany. By routine investigation,
      a second family affected with NCMD was detected in Germany. As some authors still
      doubt the good prognosis of this disease, our results should be added to the
      experience of others. PATIENTS AND METHODS: In a total of 18 family members from
      three generations between the age of 2 and 65 years, clinical investigations and
      genetic analysis was carried out. Some individuals had additional examinations
      such as colour contrast sensitivity, EOG, ERG, and microperimetry. RESULTS: Ten
      of 18 family members turned out to be affected. All grades of NCMD were present
      with great variability. Visual acuity ranged from 0.32 to 1.0 and did not
      correlate to the grade of the disease or to the age of the person. In those
      patients who underwent microperimetry, central fixation was confirmed. Genetic
      linkage analysis further narrowed the region harbouring the NCMD locus and
      supported the assumption that the central areolar pigment epithelial dystrophy
      (CAPED) is an allelic disorder. CONCLUSION: Similar visual acuity in three
      generations of NCMD patients supports the observation that NCMD is not a
      progressive disorder. If geographic atrophy is found in a patient with good
      visual acuity, NCMD should be considered and genetic analysis should be carried
      out.

PMID- 9531797
TI  - [Model for cost-benefit relations of amblyopia screening].
AB  - BACKGROUND AND PURPOSE: In Germany, 750,000 children are born per year who should
      be screened for developmental visual defects in the age range 24-48 months.
      However, the established pediatric screening program is not sufficient to prevent
      amblyopia. The purpose of this study was to examine the cost-effectiveness of
      alternatives for amblyopia and microtropia screening. METHODS: Three options were
      compared: (1) an orthoptic screening carried out in the field, for instance in
      kindergartens, (2) an examiner-independent objective apparatus-based screening,
      and (3) a complete ophthalmological and strabismological examination carried out
      in a practice. The costs of screening, follow-up examinations and of the
      treatment were modelled for prevalences of 1% (microtropia) and 5% (amblyopia).
      The benefit due to treatment was calculated as the result of an avoided whole
      person impairment of 3% and 1%. The income related, increased tax and health care
      payments were used to cover the costs. RESULTS AND CONCLUSIONS: In options (1)
      and (2) there were favorable cost-effective ratios. The practice-based option 3
      was economically less promising. The higher the prevalence was, the higher the
      resulting cost-effectiveness.

PMID- 9531798
TI  - [Neurophysiologic follow-up in patients with hypophyseal adenoma operations].
AB  - BACKGROUND: Pituitary tumors are adenomas of a region of the sella turcica which
      can produce compression of the anterior visual pathway. PATIENTS AND METHODS:
      Besides clinical signs of visual improvement such as enhanced visual acuity and
      visual field, the use of electroophthalmological methods can help monitor
      patients after neurosurgery. RESULTS: The N75 P100 amplitude of the p-VEP has
      proven to be the most sensitive marker for measuring-improvements after surgery.
      This amplitude significantly increased, whereas latency time, visual acuity and
      visual field showed no statistically significant changes after surgery.
      CONCLUSIONS: The p-VEP is an important tool in treating patients with compression
      of the visual pathway.

PMID- 9531799
TI  - [Endoscopically controlled erbium YAG laser goniotomy. Initial preclinical
      trials].
AB  - INTRODUCTION: Endoscopic erbium-YAG laser treatment is a new approach in glaucoma
      surgery. In contrast to conventional laser systems, the photoablative erbium-YAG
      laser allows microperforations of the trabecular meshwork without thermal side
      effects. We report our first preclinical trials using this new system. METHOD: We
      used the Endognost system (Schwind Co.). The device combines an endoscope and
      illumination fiber (0.5 mm diameter), laser fiber (0.5 mm) and a irrigation tube
      in one probe with a 1.1 mm external diameter. The Endognost system was tested in
      porcine and enucleated human eyes. All eyes were examined histologically.
      RESULTS: The endoscopic view into the anterior chamber allows for precise
      allocation of the laser pulses. Using a single pulse mode with 10 mJ a
      micropuncture of the trabecular meshwork can be achieved without damaging the
      adjacent tissue. Using multiple pulses or higher energy levels leads to damage of
      the posterior wall of Schlemm's canal and to thermal side effects. CONCLUSIONS:
      Endoscope guided erbium-YAG laser effects on trabecular tissue are comparable to
      those produced by a 308 nm excimer laser. Therefore, a similar reduction in
      intraocular pressure can be expected.

PMID- 9531800
TI  - [Glaucoma in Munster].
AB  - BACKGROUND: The question was: are all persons with glaukoma in the town of
      Munster in treatment? MATERIAL AND METHODS: The author recorded all patients with
      glaucoma and were subdivided into the different glaucoma diseases. The author
      analysed 10 glaucoma screenings of white populations published in the past 30
      years and compared these with the glaucoma population in Munster. RESULT: The
      results of these comparisons are ambiguous. In one survey (Tierp) 50% more POAG
      patients were found than are known in Munster; another (Baltimore) had the same
      distribution as Munster. CONCLUSION: With our knowledge about the course of
      untreated glaucoma, such uncertainty is, in tolerable, and the author suggests
      that glaucoma screening be offered to part of the population, like cancer
      screening.

PMID- 9531801
TI  - [Reduced visual capacity increases the risk of accidents in street traffic].
AB  - BACKGROUND: This study was carried out to investigate the relationship between
      the frequency of traffic accidents and impaired vision. MATERIALS AND METHODS:
      Seven hundred and fifty-four drivers involved in accidents were recruited, in
      addition to 250 accident-free drivers similar in age and driving experience as an
      control group. The age distribution of the persons involved in traffic accidents
      (mean 56.3 years) was similar to that of the control group (mean 57.7 years), the
      difference was not statistically significant. Both groups underwent a complete
      ophthalmological examination. RESULTS: All three types of accidents (night-time
      accidents, violations of right of way, accidents during an overtaking manoeuvre)
      had a statistically significantly higher incidence of reduced photopic visual
      acuity, mesopic vision and an increased sensitivity to glare. Some other visual
      functions were also abnormal, with differences according to the type of accident.
      In particular, there were noticeable differences between the control group and
      those who were involved in night-time accidents regarding mesopic vision and
      sensitivity to glare. Concerning mesopic vision, 15% of the 261 persons involved
      in night-time accidents did not reach the contrast limit of 1:5; with glare,
      20.7% failed. In comparison 4% of the control group reached this critical limit
      without glare and 7.6% with glare. These differences are highly statistically
      significant. In contrast to these findings, many of the drivers involved in
      accidents assessed their own visual capability as "excellent". CONCLUSIONS: The
      results of this study show that reduced mesopic vision and increased sensitivity
      to glare are accompanied by an increased risk of night-time accidents (for
      example, collisions with a non-illuminated obstacle). This emphasizes the
      importance of regular ophthalmological check-ups including visual functions such
      as mesopic vision and sensitivity to glare, which currently are not required by
      the traffic laws in Germany.

PMID- 9531802
TI  - [Eye and general illnesses in the public school for blind and visually
      handicapped students in Saarland. Developments in the last 20 years].
AB  - BACKGROUND: The aim of the study was the evaluation of how ophthalmological
      diagnoses and the proportion of multiply handicapped children has changed within
      the last 20 years at a state school for visually handicapped and blind children.
      PATIENTS AND METHODS: A profile investigation was conducted on all 105 children
      at the Landesschule fur Blinde und Sehbehinderte des Saarlandes and compared to
      the results of an examination from 1975. RESULTS: The predominant
      ophthalmological diagnoses were: optic atrophy (17.5%), ocular albinism (11.9%),
      scar-stage IV and V of retinopathy of prematurity (11.1%), as well as
      tapetoretinal dystrophies with related syndromes (8.7%) and myopia magna (7.9%).
      Blind: 10.3% (1975: 36.4%); visually handicapped: 47.1% (1975: 49.2%); multiply
      handicapped: 42.5% (1975: 14.4%). CONCLUSIONS: (1) The diseases that dominated in
      earlier years in schools for the visually handicapped have become rare (cataract,
      aphakia, buphthalmia, macular dystrophy--all less than 5%); (2) the proportion of
      completely blind pupils has become much smaller; (3) there is an increasing
      tendency to educate visually handicapped pupils in regular schools with
      integrative aids; (4) there is also an increasing proportion of multiply
      handicapped children (school and kindergarten: 42%, early patronage 74%).

PMID- 9531803
TI  - [Stabbing pain, conjunctival changes, foreign body sensation and unilateral red
      eye. Subconjunctival macrofilariasis in systemic Loa loa filariasis].

PMID- 9531804
TI  - [Drug targeting in cytomegalovirus retinitis. Intravitreal implantation of
      ganciclovir drug carriers].

PMID- 9531805
TI  - [Cataract operation in diabetic patients].

PMID- 9531806
TI  - [Dream contents of sleep disordered patients].
AB  - The present study investigates dreams reports of patients with sleep disorders.
      Whereas, the findings scarcely showed specific dream contents for different sleep
      disorders, e.g. problematic dreams in insomniacs, breathing-related dreams in
      sleep-apnea-patients, a remarkable relationship between waking life and dream
      contents did occur. Private problems and occupational stress are reflected in
      dreams by means of increased negative feelings, aggression and occupational
      themes. The results suggest that dreams can be made use of in psychological
      invention methods in sleep disorders, e.g. stress management.

PMID- 9531808
TI  - [Roommate in patients' rooms--a nuisance or useful resources?].
AB  - A random sample (n = 80) of depressive and CHD general hospital inpatients of
      both sexes assessed fellow patients via a questionnaire (Mink) based on a
      qualitative pilot study. The results document the central role of hospital
      roommates in determining inpatient experience. Except for depressive males, all
      patients, regardless of their sex and diagnosis, experienced the presence of
      roommates as desirable and helpful. The stress factor, on the other hand,
      received a much lower rating. The main expectation was emotional relief, although
      the individual accentuation differed considerably. Putting one's complaints in
      perspective proved to be particularly important. At the same time, it became
      evident that patients, mainly males, had a fear of their roommates causing
      additional stress by illness, problems and disturbing behaviour. Male patients
      placed more emphasis on informational support aspects and, if possible, depended
      on spouses for stabilisation of their emotional balance. Female patients, on the
      other hand, described their relationships to roommates as being characterised by
      trust and understanding. At the same time, the inability to be alone was
      mentioned as a stress factor, particularly by the depressive females. The
      response pattern of the CHD patients also differed according to sex.

PMID- 9531807
TI  - [Psychological comorbidity in patients with alarming chest pain symptoms].
AB  - About 1/3 of patients with chest pain undergoing coronary arteriography (CA) have
      no coronary artery disease (CAD). Individuals with non-CAD chest pain may be
      younger and more likely to be female; they may express higher degrees of
      neuroticism. Are those features stable enough to justifi; exclusion from CA if
      present? To investigate this issue, data on psychodiagnostic parameters
      (depression, anxiety, somatic complaints) were obtained in patients before this
      were referred to CA. Inclusion criteria were a chief complaint of chest pain with
      episodes of angina-like pain at rest, suspicious enough to warrant cardiac
      catherisation; and no prior history of CAD or other organic heart disease. The
      sample consisted of 77 patients, recruited from 89 eligible patients. 12 patients
      were excluded because CA findings were missing for multiple reasons. CA was
      conducted by Judkins technique. Patients were labeled as CAD (-) if no stenosis
      were detectable. In 50 (65%) of cases CA findings were positive and in 27 (35%)
      findings were negative. CAD+ were significantly older (p < 0.05); the superiority
      in both groups were male. Prevalence of emotional disorders was markedly more
      pronounced in both groups in comparison to the normal population and to a group
      of male myocardial infarction survivors. However, those features did not
      discriminate between the groups. Long acting chest pain was predictive for high
      degrees of emotional disability (relative risk 5.33; 95% Kl 1.6-61.6; p < 0.012).
      Chest pain at rest is a major source of anxiety, depression and subsequent
      somatic preoccupation despite its ischaemic or functional origin. It leads to
      clinically relevant adjustment disorders in a significant proportion of chest
      pain patients and triggers emotional disstress. These factors may thus have less
      impact on risk stratification than expected.

PMID- 9531809
TI  - [Education in psychosomatic medicine and psychotherapy specialty: evaluation by
      students].
AB  - In the context of evaluation, experiences, attitudes, expectations and
      assessments concerning teaching psychosomatic medicine and psychotherapy were
      examined. For that purpose students of the winter term 1993/94 were given a
      questionnaire before and after the practical course. The students had little
      experience with the subject. They described low expectations regarding the
      training. However, they showed a very positive attitude towards the subject.
      After the course, they judged the training positively. In particular, the
      affective-subjective contents, considered as being typical for the subject,
      correlated with positive judgements of the teaching. Thus, in may be concluded
      that these aspects may be conveyed to the students by means of a Balint-like
      method of teaching and that these aspects are accepted by the students.

PMID- 9531810
TI  - [Correlation between dental status and dental anxiety].
AB  - The relationship between dental status and dental anxiety was analysed in 165
      patients. To assess the dental status, D3.4 MFS-index and Bleeding-on-Probing
      Index (BOP) were applied. Dental anxiety was assessed using dental anxiety
      rating, whereas aspects of state and trait anxiety were analysed by the State
      Trait-Anxiety Inventory. The hypothesis was: higher levels of dental anxiety lead
      to avoiding check-ups and necessary treatment, the consequence of which is a
      deterioration of the dental status. No significant correlation was found between
      dental anxiety and dental status. A significant difference was found when
      comparing patients with high or low dental anxiety in respect of the D3.4 MFS
      index, whereas a different trend was found on comparing these groups for BOP
      index. In addition, a significant correlation was found between dental anxiety
      and trait anxiety. These results suggest that dental anxiety is a rather non
      specific phenomenon, since it is an aspect of proneness to anxiety. In addition,
      in patients who display considerably high dental anxiety, this may lead to
      anxiety denial and abnormal behaviour (e.g. avoidance of dental hygiene or care)
      thus contributing to further deterioration of oral health.

PMID- 9531811
TI  - [Acute myocardial infarct: thrombolysis of coronary angioplasty?].

PMID- 9531812
TI  - [Pharmacotherapy with benzodiazepines: basic principles and new developments].
AB  - Pharmacotherapy of various neurologic and psychiatric disorders is based on
      amplification of the effects of the inhibitory neurotransmitter GABA in the CNS.
      Of particular importance is the modulation of GABAA receptors by benzodiazepines.
      Their effects are activity-dependent and self limiting. With the development of
      new ligands for the benzodiazepine receptorsite selective activity-profiles with
      minimal side-effects are sought. Progress is to be expected from partial agonists
      and in particular from ligands with selectivity for receptor subtypes.

PMID- 9531813
TI  - [Correlation between serious ovarian tumors and extra-ovarian peritoneal tumors
      of the same histology].
AB  - The occurrence of serous peritoneal tumors (SPT) with the same histology as
      serous neoplasms arising within the ovary is explained by the common origin of
      the peritoneum and the ovaries from the coelomic epithelium. They occur alone or
      in combination with analogous tumors of the ovary and are often misinterpreted as
      metastatic ovarian carcinomas. Their histology shows considerable variations. As
      lesions with and without invasive properties may coexist, visible lesions should
      be resected and examined as completely as possible. The prognostic significance
      of some histological findings is still under study. It appears that besides
      invasion the grade of nuclear atypia is of importance. It is therefore possible
      that the use of cytometry provides new prognostic criteria, allowing the
      identification of high risk groups. This holds also for the malignant forms of
      SPT, which seem to have a similar prognosis to analogous tumors of the ovary. For
      this purpose, peritoneal cytology is of special value and constitutes an integral
      part of the investigations.

PMID- 9531814
TI  - [Critical evaluation of "guidelines"].

PMID- 9531815
TI  - [Clinical significance of hepatitis B virus mutants].
AB  - Hepatitis B virus (HBV) mutants have recently been identified in patients with
      acute or fulminant as well as chronic infections. Naturally occurring mutations
      have been identified in all viral genes and regulatory elements. Mutations in the
      gene coding for the hepatitis B surface antigen (HBsAg) may result in infection
      or viral persistence despite the presence of antibodies against HBsAg (anti-HBs)
      ("vaccine escape" or "immune escape"). Mutations in the gene encoding the pre
      core/core protein (pre-core stop codon mutant) result in a loss of hepatitis B e
      antigen (HBeAg) and sero-conversion to antibodies to HBeAg (anti-HBe) with
      persistence of HBV replication (HBeAg minus mutant). Mutations in the core gene
      may lead among others to an immune escape due to a T cell receptor antagonism.
      Mutations in the polymerase gene can be associated with viral persistence or
      resistance to nucleoside analogues. Thus, HBV mutations may affect the natural
      course of infection, viral clearance and response to antiviral therapy. The exact
      contribution of specific mutations to diagnosis and therapy of HBV infection as
      well as patient management in clinical practice remain to be established.

PMID- 9531816
TI  - [Status febrilis and jaundice].
AB  - A 49 year old patient was admitted with fever and jaundice. Laboratory evaluation
      showed leukocytosis, elevated values for C-reactive protein, transaminases,
      bilirubin and alkaline phosphatase. Ultrasound and subsequent CT-scan revealed
      multiple liver lesions and a liquid mass in the bursa omentalis. A CT-guided
      catheter-drainage was performed and streptococcus milleri isolated from the
      abscess and one blood culture. After empiric broad spectrum treatment with
      Piperacillin/Tazobactam (Tazobac) and Netilmicin (Netromycin), Ceftriaxon
      (Rocephin) was given for a total treatment time of 10 days. Further evaluation
      revealed a perforated peptic ulcer as possible etiology for the described
      localized infectious complication.

PMID- 9531817
TI  - [Panic disorder with agoraphobia].

PMID- 9531818
TI  - [International health reforms--has Norway been left outside?].

PMID- 9531819
TI  - [Day surgery--to simplify the simple].

PMID- 9531820
TI  - [Type 2-diabetes consists of several diseases].

PMID- 9531821
TI  - [To repair an ecosystem].

PMID- 9531822
TI  - [Clostridium difficile-associated diarrhea treated with homologous feces].
AB  - The incidence of Clostridium difficile-associated diarrhoea has increased during
      the last few years. Treatment with vankomycin or metronidazol is usually
      effective, but relapses are not uncommon. Some good results have been reported
      with faecal enemas, but it is a controversal form of treatment. 18 patients with
      C. difficile-associated diarrhoea were given homologous faeces from one healthy
      donor. In 17 patients faeces was instillated via a coloscope and in one patient
      via a gastrostoma. C. difficile toxin was detected in all patients. Three
      patients with severe colitis did not respond to the treatment. The remaining
      patients were clinically cured, and no relapses were observed. Treatment of C.
      difficile-associated diarrhoea with faeces appears to be an alternative in
      moderate cases. In our limited number of patients we observed a poor correlation
      between the clinical picture, the endoscopic findings and the histological
      findings in colon biopsies. The ethical aspects of treatment with faeces will
      continue to be subject to discussion.

PMID- 9531823
TI  - [Ambulatory tonsillectomy. Is postoperative hemorrhage a risk factor?].
AB  - Out-patient surgery is being used increasingly to improve health care efficiency.
      In Norway, tonsillectomy is performed on an in-patient basis because of concern
      for the safety regarding primary haemorrhage. This study aims at investigating
      the safety of out-patient tonsillectomy by defining the incidence and timing of
      primary haemorrhage, thereby establishing a safe time period span for a possible
      discharge on the same day. Retrospectively recorded data on 1,632 tonsillectomies
      were reviewed. Serious primary post-tonsillectomy haemorrhage arose in 24
      patients (1.5%). In view of the fact that one fifth of these tonsillectomy
      patients experience a serious primary post-tonsillectomy haemorrhage more than
      eight hours after the operation, tonsillectomy cannot be recommended as a safe
      routine out-patient procedure.

PMID- 9531824
TI  - [Biopsy in non-neoplastic skin diseases].
AB  - The Department of Dermatology at Ulleval Hospital wanted to reveal any
      diagnostical problems with skin biopsies taken from patients in the Out-patient
      Clinic. 200 non-tumour skin biopsies from 200 patients were studied
      retrospectively (100 biopsies from 1986 and 100 from 1995/96). The tentative
      diagnosis coincided with the pathological anatomical diagnosis in 57.5%(n = 115)
      of the cases. Of the 200 patients, 22%(n = 44) had still not been given a
      specific diagnosis after biopsy. This study indicates that skin biopsy is of
      diagnostical help, but that closer cooperation between the pathologist and the
      clinician is probably necessary in order to increase the proportion of specific
      dermatological diagnoses.

PMID- 9531825
TI  - [Schistosomiasis of the urinary bladder].
AB  - A 12 year old male immigrant from Somalia was admitted to hospital after several
      years of haematuria and dysuria. Microscopic examination of the urine revealed
      eggs of the Schistosoma haematobium. Urine culture was negative. Cystoscopy
      showed a characteristic bilharzial tubercle, and numerous sandy patches were also
      seen. Mucosal biopsy showed schistosoma eggs, some with calcification. There was
      squamous cell metaplasia and infiltration of plasma cells and eosinofilic
      granulocytes. The patient was treated with praziquantel 600 mg x 4 for two days.
      Three months later no schistosoma eggs were seen in his urine and cystoscopy was
      negative. In immigrants from countries where bilharzia is endemic, it should be
      considered a differential diagnosis in patients with haematuria.

PMID- 9531826
TI  - [Large granular lymphocytic leukemia].
AB  - Large granular lymphocyte leukaemia (LGL leukaemia) is a rare, chronic
      lymphoproliferative bone marrow disease which can be considered a subtype of
      chronic T-cell lymphocytic leukaemia (T-CLL). We describe three patients with
      large granular lymphocyte leukaemia. They all suffered from chronic disease with
      neutropenia and relative lymphocytosis. An expansion of mature lymphocytes with
      the CD3+, CD8+, CD57+ immunophenotype was demonstrated in all three patients. Two
      patients had a history of recurring infections. Serological findings compatible
      with rheumatic disease were present in all three patients, and two suffered from
      rheumatoid arthritis. We have made a brief survey of this disease, which is
      characterized by relative or absolute lymphocytosis, neutropenia, and an
      increased risk of infection. Rheumatoid arthritis and other associated autoimmune
      manifestations occur frequently. Large granular lymphocyte leukaemia should be
      considered a possible diagnosis in patients with chronic neutropenia and relative
      lymphocytosis, in particular if rheumatic manifestations are also present. Flow
      cytometric immunophenotyping is a sensitive method in diagnosing this disease.

PMID- 9531827
TI  - [Neuralgic amyotrophy].
AB  - Neuralgic amyotrophy is an inflammatory condition of the nerves of the brachial
      plexus, the cause of which is unknown. Clinically, it presents as acute, severe
      pain in the shoulder girdle, followed by paresthesia and flaccid paralysis of
      selected muscles in the upper limb. In its initial stages, the disease may easily
      be misdiagnosed as a musculoskeletal disorder. We describe a 38-year-old man who
      experienced acute, severe pain in both shoulders, and hypoesthesia and
      paresthesias in the right arm without preceeding trauma. The condition was first
      diagnosed as capsulitis of the shoulder joint, and the patient was treated with
      naproxen with no effect. Eight days after onset of the disease, flaccid paralysis
      occurred abruptly in the right biceps muscle and in the left spinati and serratus
      anterior muscles. Sensibility and muscle strength improved gradually without
      treatment during the following months.

PMID- 9531828
TI  - [Cervical pregnancy treated with methotrexate].
AB  - Cervical pregnancy is a rare occurrence, and evacuation can induce uncontrollable
      bleeding, requiring emergency hysterectomy. Where a cervical pregnancy is
      diagnosed at an early stage, conservative treatment is preferred to surgery.
      Vaginal sonographic examination is helpful in making an early diagnosis. The
      effect of treatment can be monitored by measuring beta human chorionic
      gonadotrophin (beta-hCG) in serum. A case of cervical pregnancy which was treated
      successfully with methotrexate administered systemically is reported.

PMID- 9531829
TI  - [Non-insulin dependent diabetes in children and adolescents].
AB  - Maturity-onset diabetes of the young (MODY) is a clinically and genetically
      heterogenous disorder characterized by autosomal dominant inheritance with onset
      usually before 25 years of age, and a primary defect in glucose-stimulated
      insulin secretion. Genetic analyses have shown that mutations in at least five
      different genes can cause MODY. These are the genes encoding the glycolytic
      enzyme glucokinase, three liver-enriched transcription factors, hepatocyte
      nuclear factor (HNF)-1 alpha, HNF-1 beta and HNF-4 alpha, and the gene encoding
      the transcription factor, insulin promoter factor-1 (IPF-1). Patients with MODY3
      run a considerable risk of developing diabetic eye disease. MODY2, related to
      glucokinase deficiency, is a relatively benign disorder which does not usually
      require insulin. Experiences with the three other MODY forms have so far been
      restricted to very few families. We present the first Norwegian family with
      MODY2. Furthermore, a previously published Norwegian family is shown to be MODY3.
      Subjects who fulfil the criteria of MODY can, by genetic testing, gain
      information important for prognosis and perhaps also for therapy.

PMID- 9531830
TI  - [Genetic causes of type 2 diabetes].
AB  - The characterisation of the intracellular signal transmission regulating the
      secretion of insulin from the beta cells of the pancreatic islets has enabled the
      initiation of massive effort to find the genetic causes of beta cell dysfunction
      in Type II diabetes. The search for genetic determinants began when several genes
      involved in the mechanisms of insulin secretion were cloned in the human genoma,
      and when informative polymorphism was described within or in the vicinity of
      these genes. The rational approach to identify the putative genes causing
      diabetes would be to examine genes which encode for proteins likely to be
      important in the beta cell control of insulin secretion. A large number of
      mutations which cause Type II diabetes have been found recently. Type II diabetes
      is therefore probably a heterogenous disease, with a polygenic inheritance of a
      combination of major and minor genes affecting obesity, insulin secretion, and
      insulin action. Thus, a genotypic classification of Type II diabetes will
      eventually be possible, and it might also be possible to explain the sometimes
      puzzling observations made in diabetes research by the heterogeneity of Type II
      diabetes and the interaction between environmental and genetic factors.

PMID- 9531831
TI  - [Diphosphonates--pharmacology and clinical use].
AB  - Based upon recent research, bisphosphonates have now attained a ranking as the
      first alternative to oestrogen replacement therapy in women with postmenopausal
      osteoporosis. The efficacy of these drugs has been clearly documented in recent
      years, particularly as a result of extensive clinical trials with alendronate.
      The studies have also confirmed the favourable risk/benefit ratio. The specific
      affinity of bisphosphonates for bone tissue has been recognized for many years,
      and explains the diagnostic use of radio-labelled species in skeleton
      scintigraphy. Bisphosphonates deposited in bone tissue reverse the osteoporotic
      process by inhibiting osteoclastic bone resorption. This mechanism also explains
      their role as the treatment of choice in patients with Paget's disease and cancer
      induced hypercalcaemia. In addition, the same drugs are useful adjuvants in the
      treatment of patients with multiple myeloma or bone metastases to lessen the pain
      and risk of fracture. A possible role of bisphosphonates in the management of
      cancer patients without detectable bone metastases or patients with rheumatoid
      arthritis has been discussed, but further research is needed in these areas.

PMID- 9531832
TI  - [Competence centers fo clinical skills for general practitioners].
AB  - For a number of years not enough attention has been paid to training in practical
      skills, neither in pre- nor postgraduate medical education. Lack of training and
      experience poses particular problems for the general practitioner, who often
      works alone with little opportunity for assessment by and feedback from
      colleagues. The Clinical Skills Training Centre was established to develop and
      implement methods for training general practitioners in clinical skills. Its main
      objective is to develop teaching methods that will encourage doctors to adapt
      their professional behaviour as and when necessary. The centre has developed a
      series of short, 2-day courses for small groups of 10-12 participants where focus
      is on selected clinical topics. The courses are continuously evaluated including
      assessment by the participants themselves of their procedural proficiency.
      Results are encouraging, with the majority of doctors reporting implementation of
      one or more of the relevant procedures at the final evaluation. An interesting
      new concept is a programme of reciprocal visits among groups of 10 to 12 general
      practitioners. The intention of the programme is to break the isolation of the
      consultation and utilize the potential for learning that exists when colleagues
      are able to observe each other at work and draw on each other's experiences.

PMID- 9531833
TI  - [Local monitoring center for clozapine (Leponex) treatment].
AB  - A local centre for monitoring clozapine therapy has been in operation in the
      Pharmacy Department at Asgard Hospital in Tromso since 1994. The centre utilizes
      an electronic reporting system and is available to clozapine-prescribers in the
      three northernmost countries in Norway: Nordland, Troms and Finnmark. The system
      fosters early detection of poor compliance with frequent blood tests and for
      signs of white blood cell suppression. This is a new concept in Norway and one
      way of assuring the quality of clozapine treatment. The purpose of the centre is
      to improve patient safety by facilitating early detection of potentially
      dangerous white blood cell suppression, thereby avoiding fatal consequences.

PMID- 9531834
TI  - [Accidental administration of racemic adrenaline. Three life-threatening cases
      after intravenous injection in children].
AB  - The inhalation of racemic adrenalin is an important part of the treatment of
      inflammatory airway obstruction in children. In Norway during the last few years
      there have been several cases of adrenal solutions intended only for inhalation
      being accidentally administered as intravenous injections. The solution for
      inhalation contains an adrenalin concentration 110 times greater than the
      adrenalin intended for emergency use (0.1 mg/ml). The instant consequences of
      intravenous injections of inhalation adrenalin include arterial hypertension
      followed by hypotension, cardiac ischemia and cardiac insufficiency, pulmonary
      oedema, and respiratory failure and the need for artificial ventilation. The
      clinical picture in the three patients we describe was very dramatic. The
      injected doses were 0.16-1.1 mg l-adrenalin per kg body weight. All children
      survived without sequelae. In order to reduce the risk of accidentally
      administering intravenous injections of adrenalin intended for inhalation a set
      of guidelines is being proposed.

PMID- 9531835
TI  - [Ethical rules for physicians].

PMID- 9531836
TI  - [Social inequality and health--and so what?].

PMID- 9531837
TI  - [Tidsskrift and the mass media].

PMID- 9531838
TI  - [Are physicians allowed to test for HIV without patients' consent?].

PMID- 9531839
TI  - [Thrombosis prevention after hip arthroplasty].

PMID- 9531840
TI  - [Bronchial rupture].

PMID- 9531841
TI  - [Are we careful about alpha-streptococci?].

PMID- 9531842
TI  - [Cohort of newborn infants--we need more knowledge about causes of diseases].

PMID- 9531843
TI  - [Mercury exposure from amalgam].

PMID- 9531846
TI  - [Information on research and suicide prevention on the Internet].

PMID- 9531847
TI  - [The significance of medical judgement for medical insurance].

PMID- 9531848
TI  - [Expanded ambulatory physiotherapy (EAP) and ambulatory orthopedic trauma
      rehabilitation (AOTR)].
AB  - Orthopaedic rehabilitation for outpatients in Germany called EAP/AOTR is a new
      and complex therapy which combines elements of physical therapy and orthopaedic
      rehabilitation that so far have only been applied separately. This sophisticated
      therapy is based on individually made up plan of treatment, supervised by a
      specialist. Its aim is to substitute/shorten inpatient treatment and inability to
      work. Indications are strictly stipulated and differ among the various health
      insurance companies and state pension authorities. Undue increase in indication,
      in duration of treatment and thus in cost led to criticism by the above mentioned
      institutions. This effective treatment will eventually hold an eminent place in
      medical care if proper attention is paid to efficient control, adherence to basic
      agreement and requirements, scientific research and evaluation, as well as to
      increase consultation of specialists, qualified in physical rehabilitation. To
      renounce outpatient treatment as an alternative to inpatient treatment is
      unreasonable from a medical point of view and is quite impossible with regard to
      cost.

PMID- 9531849
TI  - [Fibromyalgia--a dispensable disease term?].
AB  - The term of "fibromyalgia" has been used increasingly in the last years for
      chronic widespread pain in particular concerning soft tissues, muscular and extra
      articular system including pain in 11 of 18 tender point sites on digital
      palpation. Scientific proof of an organic disorder could not be established to
      this day. Psychological causes are more and more considered to be responsible for
      this problems. Nowadays a psychosomatic disorder is assumed although as well a
      depression with somatization or a neurosis are discussed. Therapeutical problems
      and pain coping strategies are described just as the medico-legal assessment for
      pension scheme. Because the term "fibromyalgia" suggests an organic disorder
      which does not exist, it seems instead useful to prefer the terms "somatization
      disorder" or "pain disorder" to make easier the approach to early psychotherapy
      and to prevent a further chronification.

PMID- 9531850
TI  - [The performance evaluation of patients with osteoporosis].
AB  - Osteoporosis causes fractures of bones and thus disabilities. Patients with
      osteoporosis experience limitations in daily life and profession life. Rating of
      the disease is a prerequisite of judging the capability to work and keep on
      professional life. Osteoporosis is defined by a reduction of bone mineral density
      which is more than -2.5 standard deviations below mean peak bone mass. Severe or
      advanced osteoporosis is characterized by the occurrence of first atraumatic
      fractures. Expert advice has to consider that certain professions may cause
      deterioration of the disease and the disease itself may be incompatible with
      professional life.

PMID- 9531851
TI  - [Occupational spinal diseases in health care workers--epidemiologic and insurance
      compensation aspects (II). Part 2: The Freiburg spinal studies].

PMID- 9531852
TI  - [Critical commentary about the CARE study].
AB  - After a brief description of the CARE-Study this paper demonstrates:
      Complications of the coronary arteriosclerosis occur independent of the
      cholesterol- and LDL concentrations. Consequences are discussed.

PMID- 9531853
TI  - Effects of space flight on GLUT-4 content in rat plantaris muscle.
AB  - The effects of 14 days of space flight on the glucose transporter protein (GLUT
      4) were studied in the plantaris muscle of growing 9-week-old, male Sprague
      Dawley rats. The rats were randomly separated into five groups: pre-flight
      vivarium ground controls (PF-VC) sacrificed approximately 2 h after launch;
      flight groups sacrificed either approximately 5 h (F-R0) or 9 days (F-R9) after
      the return from space; and synchronous ground controls (SC-R0 and SC-R9)
      sacrificed at the same time as the respective flight groups. The flight groups F
      R0 and F-R9 were exposed to micro-gravity for 14 days in the Spacelab module
      located in the cargo bay of the shuttle transport system--58 of the manned Space
      Shuttle for the NASA mission named "Spacelab Life Sciences 2". Body weight and
      plantaris weight of SC-R0 and F-R0 were significantly higher than those of PF-VC.
      Neither body weight nor plantaris muscle weight in either group had changed 9
      days after the return from space. As a result, body weight and plantaris muscle
      weight did not differ between the flight and synchronous control groups at any of
      the time points investigated. The GLUT-4-content (cpm/microgram membrane protein)
      in the plantaris muscle did not show any significant change in response to 14
      days of space flight or 9 days after return. Similarly, citrate synthase activity
      did not change during the course of the space flight or the recovery period.
      These results suggest that 14 days of space flight does not affect muscle mass or
      GLUT-4 content of the fast-twitch plantaris muscle in the rat.

PMID- 9531854
TI  - Detrimental effect of hypothermia during acute normovolaemic haemodilution in
      anaesthetized cats.
AB  - Haemodynamic responses to hypothermia were studied at normal haematocrit and
      following the induction of acute normovolaemic haemodilution. Experiments were
      performed on 20 cats anaesthetized with a mixture of chloralose and urethane in
      two groups. In one group (n = 10) the effects of hypothermia on various
      haemodynamic variables were studied at normal haematocrit (41.0 +/- 1.7%) and in
      the second group of cats (n = 10) the effects of hypothermia on various
      haemodynamic variables were studied after the induction of acute normovolaemic
      haemodilution (14.0 +/- 1.0%). The haemodynamic variables left ventricular
      pressure, left ventricular contractility, arterial blood pressure, heart rate and
      right atrial pressure were recorded on a polygraph. Cardiac output was measured
      using a cardiac output computer. In both groups hypothermia was induced by
      surface cooling with the help of ice. Cardiovascular variables were recorded at
      each 1 degree C fall in body temperature. Hypothermia produced a significant (P <
      0.05) drop in heart rate, cardiac output, arterial blood pressure and left
      ventricular contractility in both groups. However, the percentage decrease in
      these variables in response to hypothermia was significantly (P < 0.05) higher in
      cats with low haematocrit than in those with normal haematocrit. The severity of
      hypothermia--induced cardiovascular effects is evident from the drastic decrease
      in heart rate, cardiac output, arterial blood pressure and myocardial
      contractility in cats with low haematocrit, indicating a higher risk of
      circulatory failure under anaemic conditions at low temperatures.

PMID- 9531855
TI  - Body composition in air and road inductees at high altitude during the initial
      days of acclimatization.
AB  - This study assesses body composition changes and their time course during the
      initial days of acclimatization to high altitude (HA). Comparisons were made
      between gradual and acute induction to HA using 60 male lowlander volunteers (24
      28 years of age) divided into two equal groups for inducting them to HA. Thirty
      subjects were air-lifted from sea level (SL) to 3500 m HA in 1 h. These subjects
      were air inductees (AI). The other 30 subjects were transported in 4 days by road
      to the same location at 3500 m. These were road inductees (RI). After remaining
      for 15 days at 3500 m both groups were inducted to 4200 m by road. All the
      subjects could not reach the various altitudes at the same time due to logistical
      problems. Ultimately, data for each altitude (SL, 3500 m and 4200 m) were
      available for only 26 RI subjects and 10 AI subjects. Skinfold thickness (SKF)
      measurements for the subscapular, thigh, triceps, biceps, juxtanipple, umbilicus,
      suprailiac and calf regions were taken in order to calculate fat percentages.
      Measurements were taken at SL and on days 1 and 9 at both 3500 m and 4200 m. On
      day 1 at 3500 m, RI showed a significant fall in body weight (BW) with respect to
      SL but AI maintained it. On subsequent days at HA both groups showed a
      significant fall in BW and lean body mass but not in percentage fat. SKF in the
      biceps and triceps regions decreased significantly but in the umbilicus and
      suprailiac regions it significantly increased at HA in both groups. Body
      composition, along with other parameters, is discussed determining the
      acclimatization schedule for sojourners at HA. Possibly, translocation of body
      fat takes place from the periphery to deep body fat depots in the core/main trunk
      due to the cold at HA.

PMID- 9531856
TI  - Shinrin-yoku (forest-air bathing and walking) effectively decreases blood glucose
      levels in diabetic patients.
AB  - The influence of "shinrin-yoku" (forest-air bathing and walking) on blood glucose
      levels in diabetic patients was examined. Eighty-seven (29 male and 58 female)
      non-insulin-dependent diabetic patients [61 (SEM 1) years old] participated in
      the present study. Shinrin-yoku was performed nine times over a period of 6
      years. The patients were divided into two parties. They then walked in the forest
      for 3 km or 6 km according to their physical ability and/or the existence of
      diabetic complications. The mean blood glucose level after forest walking changed
      from 179 (SEM 4) mg.100 ml-1 to 108 (SEM 2) mg.100 ml-1 (P < 0.0001). The level
      of glycated haemoglobin A1c also decreased from 6.9 (SEM 0.2)% (before the first
      shinrin-yoku) to 6.5 (SEM 0.1)% (after the last shinrin-yoku; P < 0.05). Blood
      glucose values declined by 74 (SEM 9) mg.100 ml-1 and 70 (SEM 4) mg.100 ml-1
      after short- and long-distance walking respectively. There was no significant
      difference between these values. Since the forest environment causes changes in
      hormonal secretion and autonomic nervous functions, it is presumed that, in
      addition to the increased calorie consumption and improved insulin sensitivity,
      walking in a forest environment has other beneficial effects in decreasing blood
      glucose levels.

PMID- 9531857
TI  - UVB radiation and its role in the treatment of postmenopausal women with
      osteoporosis.
AB  - In humans, the serum concentration of parathyroid hormone (PTH) is higher in
      winter than in summer. The increase of PTH can be suppressed by oral vitamin D
      supplements, which is considered beneficial to those with osteoporosis. The
      present study investigates whether this effect can also be achieved by serial
      ultraviolet (UV) irradiation of the skin. In total, 34 women suffering from
      postmenopausal osteoporosis were included in the open trial. In late winter, 20
      patients were irradiated with a spectrum containing UVB, eight times over a
      period of 4 weeks. The serum concentrations of 25-hydroxyvitamin D [25(OH)D],
      1,25-dihydroxyvitamin D [1,25(OH)2D], PTH, osteocalcin, alkaline phosphatase
      (AP), calcium and phosphorus were measured before the first, and 2 days after the
      last, dose of radiation. The data were compared to the controls (n = 14, no UV
      exposure), who were evaluated once at the start of the study and then again 4
      weeks later. After UV irradiation the level of 25(OH)D was increased, whilst that
      of PTH remained unchanged. The serum level of osteocalcin decreased in the
      control group, but did not change in the group of women who had been exposed to
      UV radiation. The present study of osteoporotic women does not confirm previous
      findings in studies of healthy volunteers i.e. that PTH can be suppressed by
      exposure to UVB radiation in winter. Further studies are required to specify
      whether there are subgroups of osteoporotic people who may benefit from exposure
      to UVB radiation during winter.

PMID- 9531859
TI  - Psychoanalysis: a dysfunctional family?
AB  - The discussion opens with an account of the author's mother's bizarre family in
      which a strong, charismatic grandmother maintained absolute control over her
      large family by encouraging a neurotic dependence in them through daily reports
      of their complaints. Getting interested in psychoanalysis in an effort to
      understand the dynamics of this dysfunctional family, the author, a biographer,
      turned to the study of Melanie Klein, becoming entranced by her ideas. Her
      research also revealed how Klein had discouraged her followers from developing
      ideas that diverged in any way from her own. Her portrait of the pioneer analyst
      provoked intense indignation. A similar pattern of absolute loyalty to his person
      and theories was to be found in Freud's Secret Committee, formed primarily as a
      means of getting rid of Jung who had been showing disturbing signs of
      independence. When Ferenczi and Rank began to pursue independent lines of enquiry
      in their work, they too were though to be undermining the foundations of
      classical psychoanalysis. Finally, the author concludes that though there have
      been sorry incidents in psychoanalysis, we should be mature enough to accept both
      the contributions of the early pioneers and the realizations that new ideas must
      be permitted to evolve.

PMID- 9531858
TI  - The effect of exposure to negative air ions on the recovery of physiological
      responses after moderate endurance exercise.
AB  - This study examined the effects of negative air ion exposure on the human
      cardiovascular and endocrine systems during rest and during the recovery period
      following moderate endurance exercise. Ten healthy adult men were studied in the
      presence (8,000-10,000 cm-3) or absence (200-400 cm-3) of negative air ions (25
      degrees C, 50% humidity) after 1 h of exercise. The level of exercise was
      adjusted to represent a 50-60% load compared with the subjects' maximal oxygen
      uptake, which was determined using a bicycle ergometer in an unmodified
      environment (22-23 degrees C, 30-35% humidity, 200-400 negative air ions.cm-3).
      The diastolic blood pressure (DBP) values during the recovery period were
      significantly lower in the presence of negative ions than in their absence. The
      plasma levels of serotonin (5-HT) and dopamine (DA) were significantly lower in
      the presence of negative ions than in their absence. These results demonstrated
      that exposure to negative air ions produced a slow recovery of DBP and decreases
      in the levels of 5-HT and DA in the recovery period after moderate endurance
      exercise. 5-HT is thought to have contributed to the slow recovery of DBP.

PMID- 9531860
TI  - Ron Irvine named 1997 Louis Schmidt Laureate.

PMID- 9531861
TI  - Twenty-five years ago.

PMID- 9531862
TI  - The significance of hydrosalpinx in in vitro fertilization.
AB  - OBJECTIVE: To review the effects of hydrosalpinx on IVF/ET and the role of
      salpingectomy. DESIGN: The literature on hydrosalpinx, IVF/ET, embryotoxicity,
      and salpingectomy for hydrosalpinx was identified through MEDLINE searches and
      reviewed. RESULT(S): Hydrosalpinx has been associated with poor fertility
      prognosis. IVF/ET is a better alternative to tubal surgery for those patients
      with severe distal tubal disease, and it is also more cost effective. However,
      the presence of hydrosalpinx has a negative effect on IVF/ET by decreasing the
      pregnancy rates and implantation rates compared with patients undergoing IVF/ET
      for tubal disease but without hydrosalpinx. The hydrosalpingeal fluid has been
      demonstrated to be embryotoxic to developing embryos, thus leading to increased
      early pregnancy losses. Poor endometrial receptivity has also been demonstrated
      in the presence of hydrosalpinges. Removal of the hydrosalpinges leads to
      improved IVF/ET rates comparable to those patients without hydrosalpinx.
      Therefore, salpingectomy has been recommended for patients with hydrosalpinx who
      will be undergoing IVF/ET. CONCLUSION(S): The presence of hydrosalpinx has a
      negative effect on IVF/ET because of the suspected embryotoxicity of the
      hydrosalpingeal fluid. Surgical removal of the hydrosalpinx has been shown to
      improve IVF/ET rates.

PMID- 9531863
TI  - Moving toward an earlier and better understanding of perimenopause.

PMID- 9531864
TI  - Assisted reproductive technology in the United States and Canada: 1995 results
      generated from the American Society for Reproductive Medicine/Society for
      Assisted Reproductive Technology Registry.
AB  - OBJECTIVE: To summarize the procedures and outcomes of assisted reproductive
      technology (ART) initiated in the United States and Canada in 1995. DESIGN: Data
      were collected in the Society for Assisted Reproductive Technology database
      program and cycle reporting forms and were submitted to the American Society for
      Reproductive Medicine/Society for Assisted Reproductive Technology Registry.
      PARTICIPANT(S): Two hundred eighty-one programs submitted data on procedures
      performed in 1995. Data were collected after November 1996 so that outcome of all
      pregnancies established would be known. MAIN OUTCOME MEASURE(S): Procedural
      outcomes measured included clinical pregnancy, ectopic pregnancy, abortion,
      stillbirth, delivery, and congenital abnormality. RESULT(S): Programs reported
      initiating 59,142 cycles of ART treatment, including frozen embryo and donor
      oocyte cycles. Of these, 41,087 cycles initiated were IVF (with and without
      micromanipulation) with 22.5% deliveries per retrieval; 3,741 were cycles of
      gamete intrafallopian transfer with 27.0% deliveries per retrieval; 1,078 were
      cycles of zygote intrafallopian transfer with 27.9% deliveries per retrieval. In
      addition to these cycles initiated in 1995, 8,453 frozen embryo thaw procedures
      were reported, either as separate procedures or in combination with other ART
      procedures with 15.2% deliveries per transfer, 3,555 donor oocyte cycles were
      initiated with an overall success of 36.0% deliveries per transfer, 1,028
      cryopreserved embryo thaw procedures from donated oocyte procedures with an
      overall success of 16.8% deliveries per transfer, and 200 ART treatment cycles in
      which a host uterus was used were initiated with an overall success of 34.9%
      deliveries per ET. As a result of all procedures, a total of 11,631 deliveries
      were reported, resulting in 16,520 neonates. CONCLUSION(S): In 1995, there were
      more programs reporting ART treatment and a significant (19.3%) increase in
      reported cycles. In comparable cycle types, overall average success rates
      (deliveries per transfer) exhibited a 0.6% increase or a 2.5% increase over the
      rates in the 1994 reported summaries.

PMID- 9531865
TI  - Confirmation of the beneficial effects of brief coincubation of gametes in human
      in vitro fertilization.
AB  - OBJECTIVE: To confirm whether brief exposure of human oocytes to spermatozoa in
      vitro results in equivalent fertilization rates and possibly better quality
      embryos than overnight coincubation and to determine if there was a difference in
      outcome with regard to the type of culture medium used. DESIGN: Prospective
      distribution of gametes between treatments in sequential patients. SETTING:
      Assisted reproductive technology program in private hospital. PATIENT(S):
      Consecutively treated subfertile couples entering an infertility program.
      INTERVENTION(S): Assisted reproductive technology treatment for infertility
      involving oocyte retrieval and in vitro fertilization. MAIN OUTCOME MEASURE(S):
      When possible, the outcome of fertilization and embryo quality were compared when
      gametes were coincubated for 1 hour or overnight. Two different formulations of
      human tubal fluid were compared in some cases. RESULT(S): There was no
      statistically significant difference in fertilization rates between a brief or
      overnight coincubation of gametes or between the two treatment groups with regard
      to the type of culture medium used. The quality of the embryos was significantly
      better in the 1-hour exposure group. The embryos in Basal XI human tubal fluid
      medium were of significantly better morphological quality than their siblings in
      D3+ human tubal fluid medium. CONCLUSION(S): Coincubation of oocytes and
      spermatozoa for a shorter period produced embryos of superior morphological
      quality than the generally accepted overnight protocol. A simple glucose and
      phosphate-free human tubal fluid medium resulted in early cleavage embryos of
      better morphological quality than a medium supplemented with glucose, taurine,
      and glutathione.

PMID- 9531866
TI  - Evaluation of polyethylene glycol/polylactic acid films in the prevention of
      adhesions in the rabbit adhesion formation and reformation sidewall models.
AB  - OBJECTIVE: To assess the efficacy of bioresorbable films consisting of various
      polyethylene glycol 6000 and polylactic acid block copolymers on the formation
      and reformation of adhesions in rabbit models of adhesion development between the
      sidewall to the adjacent cecum and bowel. The composition of the different
      polymers was expressed by the number of monomeric units in the block, namely,
      ethylene oxide (EO) and lactic acid (LA), respectively. DESIGN: Studies of the
      efficacy of EO/LA films were conducted in rabbit sidewall adhesion formation
      studies in the presence and absence of blood and in rabbit adhesion reformation
      studies. REPEL (Life Medical Sciences, Edison, NJ), a film of EO/LA ratio 3.0
      manufactured under commercial conditions, was also tested in these animal models.
      SETTING: University-based laboratory. ANIMALS: New Zealand white rabbits.
      INTERVENTION(S): Placement of films of various EO/LA ratios at the site of injury
      to the parietal peritoneum. MAIN OUTCOME MEASURE(S): Adhesion formation and
      reformation. RESULT(S): Films of various EO/LA ratios, Seprafilm (Genzyme,
      Cambridge, MA) and Interceed (Johnson and Johnson Medical, Arlington, TX) placed
      over an area of excised sidewall at the time of initial injury were highly
      efficacious in the prevention of adhesion formation. A film of EO/LA ratio 3.7,
      in contrast with Interceed, was also shown to maintain maximal efficacy in the
      reduction of adhesion formation in the presence of blood. Further, a film of
      EO/LA ratio 3.0 produced under commercial conditions, REPEL, was highly
      efficacious in reducing adhesion development in the rabbit models of adhesion and
      reformation. CONCLUSION(S): These studies suggest that bioresorbable EO/LA films
      reduced adhesion development in rabbit models of adhesion formation and
      reformation.

PMID- 9531867
TI  - Vaginal ultrasound probe cover leakage: implications for patient care.
AB  - OBJECTIVE: To assess the risk of probe contamination following transvaginal
      ultrasonography. DESIGN: Prospective cohort study. SETTING: University
      Infertility Center. PATIENT(S): Women undergoing transvaginal ultrasonography.
      INTERVENTION(S): One physician obtained 840 consecutive transvaginal
      ultrasonograms over nine months. Latex condoms were used to cover the probe.
      Following examination, the condoms were removed and the probe was wiped with a
      germicidal disposable cloth and left to air dry for 5 minutes. Condoms were
      filled with water and examined for leaks. MAIN OUTCOME MEASURE(S): Number of
      perforations and distance from condom tip. RESULT(S): Seventeen (2%) of 840
      condoms leaked. The mean distance from the tip to the point of leakage was 10.6
      cm +/- 2.8 (mean +/- SD; range, 7-14). Sixty-five percent of the leaks were < or
      = 10 cm from the tip. In several instances, two leaking condoms were found within
      a few examinations of each other. No visual contamination of the probe was noted.
      CONCLUSION(S): Although only 2% of condoms leaked, 65% were at distances that
      could have led to probe soiling intravaginally. While no body fluids were grossly
      visible, microscopic contamination was still possible. Since perforations were
      noted in close, and even consecutive scans, this study underscores the need for
      routine probe disinfection between examinations.

PMID- 9531868
TI  - Measuring human chorionic gonadotropin in the absence of implantation with use of
      highly sensitive urinary assays for intact beta-core and free beta epitopes.
AB  - OBJECTIVE: To determine if human chorionic gonadotropin (hCG) can be absorbed
      from the uterine cavity in the absence of an embryo. DESIGN: Prospective study.
      SETTING: University-based assisted reproduction program. PATIENT(S): Eight
      functionally agonadal patients (age range, 33-46 years) who were taking hormone
      replacement therapy so that they could receive donated oocytes. INTERVENTION(S):
      Intrauterine instillation of 50 microL of hCG (10,000 IU) during a mock cycle
      before an attempt at oocyte donation. MAIN OUTCOME MEASURE(S): Spot urine
      measurements of different hCG epitopes (intact beta, beta-core, and free beta) at
      timed intervals (12, 20, 44, and 68 hours after instillation). RESULT(S): All hCG
      epitopes were detected in the urine at the first sampling interval, and levels
      decreased in subsequent sampling intervals. Measurement of the serum hCG level
      confirmed that systemic absorption had occurred and that the urine measurements
      were not a result of specimen contamination through the cervix. CONCLUSION(S):
      hCG may be systemically absorbed into the blood through the uterine cavity, even
      in the absence of implantation, and its metabolites may be measured with use of
      highly sensitive urinary assays.

PMID- 9531869
TI  - Reduction of postsurgical adhesion formation in the rabbit uterine horn model
      with use of hyaluronate/carboxymethylcellulose gel.
AB  - OBJECTIVE: To assess the efficacy of a bioabsorbable gel for reducing primary
      postoperative adhesions. DESIGN: A randomized, prospective, blinded study.
      SETTING: Academic research environment. ANIMALS: Forty-one New Zealand Rabbits.
      INTERVENTION(S): A chemically modified hyaluronate and carboxymethylcellulose
      (HA/CMC) gel formulation was applied to a bilateral uterine horn injury.
      Postoperative adhesions were assessed at a second-look laparoscopy. MAIN OUTCOME
      MEASURE(S): The uterine horn model was shown to be adhesiogenic, with 29 (70%) of
      42 untreated uterine horns found to have adhesions. After gel treatment, 22 (55%)
      of 40 uterine horns were free of adhesions compared with 12 (30%) of 42 controls.
      RESULT(S): Animals treated with HA/CMC gel had significantly reduced postsurgical
      adhesion scores when compared with controls. CONCLUSION(S): Treatment of injured
      uterine horn with HA/CMC gel resulted in a significant reduction in postoperative
      surgical adhesions.

PMID- 9531870
TI  - Clinical and endocrine effects of a microdose GnRH agonist flare regimen
      administered to poor responders who are undergoing in vitro fertilization.
AB  - OBJECTIVE: To assess the endocrine and clinical responses to microdose GnRH
      agonist (GnRH-a) that was administered in the early follicular phase before
      controlled ovarian hyperstimulation to poor responders who were candidates for
      IVF-ET. DESIGN: Prospective nonrandomized trial with historical controls.
      SETTING: Tertiary care university-affiliated infertility practice. PATIENT(S):
      Thirty-four IVF-ET candidates with a prior poor response to a standard long
      protocol GnRH-a controlled ovarian hyperstimulation regimen (cycle A). Patients
      were divided into two groups based on their age at the initiation of cycle A
      (Group 1: < or = 39 years, n = 15; Group 2: > or = 40 years, n = 19).
      INTERVENTION(S): Low-dose oral contraceptive (x 21 d) followed by GnRH-a
      (leuprolide acetate; 40 micrograms s.c. b.i.d.) flare and urofollitropin
      initiated on day 3 of GnRH-a administration (cycle B). MAIN OUTCOME MEASURE(S):
      Comparative analysis of clinical responses (total urofollitropin dose used and
      number of oocytes retrieved as well as fertilization and clinical and ongoing
      pregnancy rates) and endocrine responses (serum E2, FSH, LH, T, and P levels)
      between cycles A and B in the two groups. Early follicular phase serum E2 and FSH
      changes in groups 1 and 2 were compared with changes in nine normal responder
      controls who were receiving a standard long-protocol GnRH-a/urofollitropin
      regimen (group 3). RESULT(S): Maximal E2 levels as well as clinical and ongoing
      pregnancy rates were higher in cycle B patients receiving microdose GnRH-a.
      Cancellation rates in cycle B were lower than in cycle A. Statistically
      significant increases in treatment day 6 serum FSH levels were noted during cycle
      B in both groups 1 and 2 but not in group 3 controls. No abnormal rises in LH, P,
      or T were noted in any of the groups. CONCLUSION(S): Microdose GnRH-a enhances
      urofollitropin response and clinical outcome in poor responders undergoing IVF
      ET. This may be due to enhanced release of early follicular phase endogenous FSH
      without concomitant deleterious rises in androgen levels or corpus luteum rescue.

PMID- 9531871
TI  - Effects of seminal plasma from cigarette smokers on sperm viability and
      longevity.
AB  - OBJECTIVE: To evaluate the effects of cigarette smoking on the ability of seminal
      plasma (SP) to maintain sperm viability. DESIGN: Clinical randomized study.
      Spermatozoa from cigarette smoking or nonsmoking subjects were reconstituted in
      SP from smokers and nonsmokers and in modified Ham's F-10 medium, followed by
      sperm quality assessment during a 48-hour incubation period. SETTING: Andrology
      Institute of Lexington, Lexington, Kentucky. PATIENT(S): Twenty men who had been
      smoking cigarettes for longer than 3 years (30 cigarettes per day or more) and 20
      nonsmokers participated in this study. MAIN OUTCOME MEASURE(S): Improvement in
      sperm viability by removal of SP--and associated detrimental factors present in
      the SP--from smoker subjects. RESULT(S): The results obtained indicate that the
      quality of spermatozoa obtained from nonsmokers was superior to that of smokers.
      The SP from the two patient groups had a definite effect on their respective
      sperm quality, i.e., beneficial effects for the nonsmokers, detrimental effects
      for the smokers. Exposure of spermatozoa from the nonsmokers to SP from the
      smokers resulted in a significant reduction in sperm viability. However, exposure
      of spermatozoa from the smokers to SP from the nonsmokers or to Ham's F-10 medium
      yielded significant improvements in sperm viability. CONCLUSION(S): The
      detrimental effects of smokers' SP on nonsmokers' spermatozoa was prominent and a
      rather unique phenomenon. The results generated in this study could be of
      clinical significance since removal of smokers' SP and subsequent reconstitution
      and incubation in physiological media seems to enhance the viability, longevity,
      and possibly the fertilizing ability of these spermatozoa for use in various
      assisted reproductive technologies.

PMID- 9531872
TI  - An electron microscope study of the axonemal ultrastructure in human spermatozoa
      from male smokers and nonsmokers.
AB  - OBJECTIVE: To investigate possible abnormalities or deterioration of the sperm
      axonemal ultrastructure in men who have smoked a large quantity of cigarettes (>
      20 per day) for a prolonged period. DESIGN: Semen specimens were collected by
      patients via masturbation; qualitative characteristics of the sperm were assessed
      and ultrastructural analysis of the sperm axoneme was performed using standard
      operating procedures for electron transmission microscopy. SETTING: The Andrology
      Institute of Lexington, Lexington, Kentucky, and the Department of Histology and
      Embryology, University of Salonika, Greece (collaborative effort). PATIENT(S):
      Twenty-nine men (mean age +/- SD, 30.7 +/- 2.1 years) who smoked a mean (+/- SD)
      of 30.7 +/- 2.1 cigarettes per day for 10.7 +/- 0.7 years and 15 men who never
      smoked (mean age +/- SD, 30.4 +/- 2.2 years) participated in this study. MAIN
      OUTCOME MEASURE(S): Ultrastructural organization of the sperm axoneme in male
      smokers and nonsmokers. RESULT(S): Changes in the number and the arrangement of
      axonemal microtubules were noted in the smoker group when compared to the
      nonsmoker group. The incidence of axonemal abnormalities was higher in
      spermatozoa from smokers compared with that in spermatozoa from nonsmokers.
      CONCLUSION(S): Smoking a large quantity of cigarettes per day, under the
      conditions of the current study, severely affected the ultrastructure of the
      flagellum and, more specifically, it affected the axoneme of the human
      spermatozoon.

PMID- 9531873
TI  - Preovulatory changes of blood flow in different regions of the human follicle.
AB  - OBJECTIVE: To assess regional changes in ultrasound-derived indices of blood flow
      in the dominant human follicle after the plasma LH surge. DESIGN: A cross
      sectional, prospective study. SETTING: Reproductive medicine unit at a
      university. PATIENT(S): Women attending an assisted conception clinic to
      determine the appropriate time to transfer previously frozen embryos during a
      natural cycle. INTERVENTION(S): Transvaginal ultrasonography with color Doppler
      imaging and pulsed Doppler spectral analysis was used to obtain indices of blood
      flow and velocity from vessels in the base, lateral part, and apex of the
      dominant follicle on days 10-12 (from day 1 of menses) and after the LH surge,
      but before rupture. Immunoassays were used to measure the blood concentrations of
      LH twice daily (at 8-10 A.M. and 4-6 P.M.) from cycle day 10. MAIN OUTCOME
      MEASURE(S): The pulsatility index (PI), resistance index (RI), peak systolic
      velocity (PSV), and time-averaged maximum velocity (TAMXV) in the uterine
      arteries and three regions of the dominant follicle (apical, lateral, and basal
      parts); follicular volume; the day and time of the onset of the LH surge (defined
      as first concentration of LH > 22 U/L) and the times of each scan. RESULT(S):
      Twenty-two women (aged 28-39 years) were studied and seven were scanned on days
      10-12. A retrospective examination of the data from the remainder showed that
      eight were scanned < 20 hours after onset of the LH surge and seven were scanned
      > 20 hours after the onset of the LH surge. There was a significant increase in
      follicular volume after the LH surge. The PI was similar in vessels from the base
      (0.86 +/- 0.11; mean +/- SEM), lateral part (0.72 +/- 0.51) and apex (0.67 +/-
      0.09) at cycle days 10-12 and then gradually decreased in the apex. There were
      similar changes in the RI. The PSV (mean +/- SEM; cm/s) was similar in vessels
      from the base (10.1 +/- 1.64), lateral side (8.2 +/- 1.43), and apex (9.2 +/-
      1.91) in follicles of days 10-12. Within 20 hours of the onset of the LH surge,
      the PSV had increased in basal vessels (23.4 +/- 4.10), remained similar in
      lateral vessels (11.64 +/- 3.18), and was undetectable in apex vessels from six
      of eight follicles. Twenty hours after the LH surge, there was no pulsatile blood
      flow observed in the apical part of the follicle, but there was a sustained high
      PSV in the base (15.73 +/- 3.42) and lateral side (9.02 +/- 1.5). There were
      corresponding changes in the TAMXV. CONCLUSION(S): During the ovulatory process
      there are prominent changes in the regional blood flow of the follicle with a
      marked increase of the flow to the base of the follicle and a concomitant
      decrease of blood flow to the apex. These changes may be essential for the
      release of a mature oocyte.

PMID- 9531874
TI  - Subcutaneous administration of a depot gonadotropin-releasing hormone agonist
      induces profound reproductive axis suppression in women.
AB  - OBJECTIVE: To compare the i.m. and s.c. routes of depot GnRH agonist
      administration. DESIGN: Prospective, controlled pharmacokinetics study. SETTING:
      Volunteers in an academic research environment. PATIENT(S): Forty women with
      benign gynecologic disorders. INTERVENTION(S): Triptorelin administration (3.75
      mg) at 28-day intervals for 6 consecutive months. Twenty patients were treated
      with IM triptorelin, and 20 patients were treated with SC triptorelin. MAIN
      OUTCOME MEASURE(S): Assessment of side effects, GnRH test results, and
      triptorelin, LH, FSH, estradiol, and progesterone levels. RESULT(S): The
      occurrence of injection site redness and itching and of some hypoestrogenic side
      effects was increased significantly in the SC group. Plasma triptorelin levels
      were significantly higher in the IM group in the first month of treatment;
      thereafter, the pattern reversed, with a nonsignificant trend toward higher
      plasma triptorelin levels in the SC group. Serum LH, FSH, estradiol, and
      progesterone levels were low after the first month of treatment and did not
      differ between the two treatment groups. On day 196 (2 months after the last
      depot triptorelin injection), triptorelin was still measurable and gonadotropins
      and gonadal steroids were still suppressed. Spontaneous menses returned
      significantly later in the SC group than in the IM group. CONCLUSION(S):
      Subcutaneous triptorelin can be administered by the patient. Both IM and SC
      triptorelin administration are cliniclly effective, but they result in different
      triptorelin pharmacokinetics. Subcutaneous triptorelin is associated with more
      prolonged amenorrhea than is IM triptorelin, suggesting enhanced pituitary
      ovarian suppression. These results suggest that SC triptorelin may allow lower
      drug dosage administration and/or longer administration intervals.

PMID- 9531875
TI  - Luteinizing hormone increases estradiol secretion but has no effect on
      progesterone concentrations in the late follicular phase of in vitro
      fertilization cycles in women treated with gonadotropin-releasing hormone agonist
      and follicle-stimulating hormone.
AB  - OBJECTIVE: To determine whether the late follicular phase increase in circulating
      P concentrations during controlled ovarian stimulation with GnRH-a and FSH can be
      influenced by addition of LH to the stimulating gonadotropin during the final 2
      days. DESIGN: Randomization of patients to receive either FSH alone or FSH with
      LH (hMG) for the final 2 days before hCG, after follicular phase stimulation with
      purified FSH. SETTING: A.C.S. Unit at the Royal Infirmary, Glasgow, U.K.
      PATIENT(S): Patients were unselected and were undergoing IVF. INTERVENTION(S):
      Patients received stimulation with purified FSH (300 IU/d) until a follicle of 15
      mm was observed; the regimen was then changed to either 225 IU of FSH or 225 IU
      of hMG. MAIN OUTCOME MEASURE(S): Estradiol and P in the peripheral circulation.
      RESULT(S): Significant increases in E2 concentration were observed, but there
      were no changes in the circulating progesterone. CONCLUSION(S): The late
      follicular phase increase in P is unrelated to any luteinizing process
      attributable to effects in the circulation or sensitization of follicular cells
      to LH.

PMID- 9531876
TI  - "Coasting" does not adversely affect cycle outcome in a subset of highly
      responsive in vitro fertilization patients.
AB  - OBJECTIVE: To study the effect of postponing hCG administration while continuing
      daily GnRH agonist therapy ("coasting") on highly responsive patients undergoing
      IVF-ET. DESIGN: Retrospective analysis. SETTING: University-affiliated Center for
      Fertility and Reproductive Medicine. PATIENT(S): Patients undergoing IVF-ET from
      March 1995 to March 1997. INTERVENTION(S): Three groups of IVF-ET patients were
      compared to explore the effect of coasting on cycle outcome: a group of highly
      responsive coasted patients, a group of equally responsive noncoasted patients,
      and an age-matched normally responsive control group. Two groups of coasted
      patients were also compared to assess the effect of E2 levels at the time that
      they met the follicular criteria for hCG administration. Last, the effect of
      varying coast duration was examined by regression analysis. MAIN OUTCOME
      MEASURE(S): Patient characteristics, outcome parameters, and incidence of ovarian
      hyperstimulation syndrome (OHSS). RESULT(S): Coasting had no detrimental effect
      on cycle outcome in the subset studied. Regression analysis, however, suggests an
      inverse relationship between coast duration and the number of mature oocytes
      retrieved as well as the clinical pregnancy rate. CONCLUSION(S): Coasting in the
      studied subset of IVF patients did not adversely affect cycle outcome parameters
      or the incidence of OHSS, but prolonged coasting intervals may impair IVF cycle
      outcome.

PMID- 9531877
TI  - Premature luteinization: could it be an early manifestation of low ovarian
      reserve?
AB  - OBJECTIVE: To gain insight into the physiologic significance of premature
      luteinization and to evaluate whether it could be a manifestation of low ovarian
      reserve. DESIGN: Retrospective evaluation. SETTING: Reproductive medicine unit.
      PATIENT(S): Thirty-one consecutively seen women with normal ovulation and
      unexplained infertility. INTERVENTION(S): Induction of superovulation with hMG
      coupled with synchronized IUI. A GnRH agonist was not used during the study. MAIN
      OUTCOME MEASURE(S): Premature luteinization was defined as a
      progesterone/estradiol ratio of > 1 on the day of hCG administration. Patients
      were evaluated during their first cycles of hMG treatment and then were divided
      into those with (study group) and those without (control group) premature
      luteinization. The ovarian reserve parameters were compared between the two
      groups. RESULT(S): Nineteen of the 31 patients with unexplained infertility
      demonstrated premature luteinization. Patient characteristics were similar
      between the study and control groups. Mean (+/- SD) day 3 FSH levels were 8.2 +/-
      3.3 and 6.6 +/- 1.7 mIU/mL in the study and control groups, respectively. Mean
      (+/- SD) day 3 estradiol levels were significantly higher in the study than in
      the control group (74 +/- 49 pg/mL vs. 30 +/- 17 pg/mL, respectively). Mean (+/-
      SD) estradiol levels on the day of hCG administration also differed significantly
      between the study and control groups (760 +/- 539 pg/mL vs. 1,568 +/- 675 pg/mL,
      respectively). Likewise, the number of follicles that were > or = 15 mm on the
      day of hCG administration was significantly lower in the study than in the
      control group (2.9 +/- 1.5 vs. 4.3 +/- 1.3, respectively). The total dose of hMG
      and duration of administration were similar in the two groups. The clinical
      pregnancy rates after four cycles of treatment were 15.8% and 41.7% in the study
      and control groups, respectively. CONCLUSION(S): This preliminary work suggests
      that, in cycles that are not treated with a GnRH agonist, signs of premature
      luteinization in patients with unexplained infertility could be an early
      manifestation of low ovarian reserve. It appears that hMG treatment in this group
      of patients could uncover the pathogenesis of their infertility.

PMID- 9531878
TI  - Transport in vitro fertilization and intracytoplasmic sperm injection: results of
      a collaborative trial.
AB  - OBJECTIVE: To determine whether the use of a central assisted reproduction
      laboratory, with gamete transport to the facility (transport assisted
      reproduction), would decrease oocyte quality or performance in IVF-ET and
      intracytoplasmic sperm injection (ICSI). DESIGN: Retrospective clinical study.
      SETTING: Public and private fertility clinics. PATIENT(S): A total of 467 couples
      underwent transport IVF, whereas 108 underwent transport ICSI. A group of 60
      couples underwent conventional IVF during the same period. All methods and
      protocols used were similar among centers. Oocyte pick-up was performed by
      ultrasound-guided vaginal puncture. INTERVENTION(S): Oocytes were transported
      under controlled conditions, from the site of follicular aspiration to a central
      laboratory. MAIN OUTCOME MEASURE(S): The fertilization and cleavage rates and
      clinical pregnancies were compared among the study populations. RESULT(S): The
      differences between the fertilization and cleavage rates of ova and the rates of
      clinical pregnancies produced by transport and conventional methods were not
      statistically significant. CONCLUSION(S): Gamete transport to a central
      laboratory was not harmful for oocytes or for the outcome of assisted
      reproduction. Transport makes the use of IVF and ICSI available to physicians who
      are not affiliated with an assisted reproduction program, reduces costs, and
      increases acceptability of the procedures to patients.

PMID- 9531879
TI  - Plasma concentrations of progesterone are higher in the uterine artery than in
      the radial artery after vaginal administration of micronized progesterone in an
      oil-based solution to postmenopausal women.
AB  - OBJECTIVE: To verify the occurrence of preferential distribution of vaginally
      administered progesterone to the uterus compared with extrapelvic regions in vivo
      and in humans. DESIGN: Prospective clinical study. SETTING: University medical
      school. PATIENT(S): Twenty postmenopausal women undergoing transabdominal
      hysterectomy for benign pathologies. INTERVENTION(S): Forty-five minutes before
      surgery, the women received a single vaginal administration of an oil-based
      micronized progesterone (100 mg) solution currently available on the market for
      IM use. During the operation, parallel blood samples were drawn from the uterine
      and radial arteries. MAIN OUTCOME MEASURE(S): Plasma levels of progesterone were
      measured by RIA. RESULT(S): Mean (+/- SD) plasma levels of progesterone were
      significantly higher in the uterine artery than in the radial artery (9.75 +/-
      3.21 vs. 5.12 +/- 2.06 ng/mL, respectively). CONCLUSION(S): Vaginal
      administration allows a preferential distribution of progesterone to the uterus,
      which confirms the existence of the so-called "first uterine pass effect."

PMID- 9531880
TI  - Inhibin-B: the physiologic basis of the clomiphene citrate challenge test for
      ovarian reserve screening.
AB  - OBJECTIVE: To determine inhibin-B concentrations during ovarian reserve screening
      in women with normal and diminished ovarian reserve as determined by the
      clomiphene citrate challenge test. DESIGN: Retrospective. SETTING: Tertiary
      fertility center. PATIENT(S): Women undergoing ovarian reserve screening for a
      routine fertility evaluation. INTERVENTION(S): Clomiphene citrate challenge test.
      MAIN OUTCOME MEASURE(S): Inhibin-B concentrations on menstrual days 3 and 10.
      RESULT(S): Nineteen patients with normal ovarian reserve and 15 with diminished
      ovarian reserve had serum inhibin-B concentrations determined during ovarian
      reserve screening. For all patients, day 10 inhibin-B concentrations were higher
      than day 3. Women with normal ovarian reserve had higher inhibin-B concentrations
      on both days 3 and 10 than women with diminished ovarian reserve. Inhibin-B
      concentrations demonstrated a negative correlation with FSH levels on both cycle
      days 3 and 10 and a positive correlation with E2 on cycle day 10. CONCLUSION(S):
      Women with diminished ovarian reserve during ovarian reserve screening had
      reduced granulosa cell inhibin-B production compared with women with normal
      ovarian reserve. The lower inhibin-B concentrations may be responsible for the
      elevated FSH concentrations and may be indicative of the aging follicular
      apparatus.

PMID- 9531882
TI  - Genetic counseling in a patient with XXY/XXXY/XY mosaic Klinefelter's syndrome:
      estimate of sex chromosome aberrations in sperm before intracytoplasmic sperm
      injection.
AB  - OBJECTIVE: To report the sex chromosome aberrations in the sperm of a patient
      with mosaic Klinefelter's syndrome before ICSI. DESIGN: Case report. SETTING:
      Institute of Human Genetics, University Hospital PATIENT(S): A patient with an
      XXY/XXXY/XY mosaic Klinefelter's syndrome and extreme oligozoospermia.
      INTERVENTION(S): Skin biopsy, buccal smear, hair root sampling, and semen
      sampling. MAIN OUTCOME MEASURE(S): The karyotypes of three additional somatic
      cell systems and the ratio of sex chromosome aberrations in sperm. RESULT(S):
      After two-color fluorescence in situ hybridization of 202 interphase sperm
      nuclei, both the proportion of hyperhaploid 24, XY and 25, XXY sperm (5.0% and
      0.5%, respectively) and of hyperhaploid 24, XX sperm (2.0%) were elevated. In
      contrast with peripheral lymphocytes, 93.9% of which showed sex chromosome
      aberrations, in the present patient only 7.5% of sperm proved to be hyperhaploid
      with an extra sex chromosome. CONCLUSION(S): The determination of sex chromosome
      aberrations in the sperm of a patient with mosaic Klinefelter's syndrome may
      provide additional information to estimate the transmission risk to his
      offspring.

PMID- 9531881
TI  - Is bed rest following embryo transfer necessary?
AB  - OBJECTIVE: To evaluate the effect of no bed rest following ET on the results of
      an IVF program. DESIGN: Historical cohort-control study. SETTING: A University
      based assisted conception unit. PATIENT(S): One thousand and nineteen (1019) IVF
      cycles were performed at our unit from June 1994 to August 1996. The historical
      control consisted of all the 19,697 IVF cycles reported in the United Kingdom
      national database from April 1994 to March 1995. INTERVENTION: No bed rest
      following ET in our patients. MAIN OUTCOME MEASURE(S): Pregnancy rate (PR) and
      clinical PR per cycles started and per ET procedure. RESULT(S): The clinical PR
      per ET was significantly higher in our patients than in the national data (30%
      versus 22.9%), as was the clinical PR per cycle (23.5% versus 18.6%). The
      implantation rate in our patients was 17.2%. CONCLUSION(S): The favorable PR in
      our patients despite no bed rest following ET suggests the bed rest is not
      necessary.

PMID- 9531883
TI  - Comparison of intrauterine insemination with timed intercourse in superovulated
      cycles with gonadotropins: a meta-analysis.
AB  - OBJECTIVE: To compare timed intercourse and IUI with the husband's sperm in
      patients with unexplained infertility who are undergoing superovulation with
      gonadotropins. DESIGN: Meta-analysis. All published reports of randomized,
      prospective studies with an English-language abstract extracted from MEDLINE were
      analyzed. A crossover search was done from the papers obtained. SETTING: Academic
      center. PATIENT(S): Couples with unexplained infertility. INTERVENTION(S): Meta
      analysis of studies evaluating patients superovulated with gonadotropins and
      randomized for timed intercourse or IUI. MAIN OUTCOME MEASURE(S): Pregnancy rates
      (PRs) were obtained. The common odds ratio (OR) and 95% confidence intervals (95%
      CI) were calculated. RESULT(S): There were 49 pregnancies in 431 cycles of timed
      intercourse (11.37%), whereas there were 110 pregnancies in 549 cycles of IUI
      (20.04%). The PRs for IUI were significantly increased compared with those for
      timed intercourse in superovulation cycles (common OR = 1.84; 95% CI = 1.30
      2.62). CONCLUSION(S): On the basis of the meta-analysis of 980 cycles in
      randomized and prospective studies, a patient's chances of becoming pregnant are
      greater with IUI with her husband's sperm than with timed intercourse in cycles
      superovulated with gonadotropins.

PMID- 9531885
TI  - Prospective evaluation of endometrial thickness as a predictor of pituitary down
      regulation after gonadotropin-releasing hormone analogue administration in an in
      vitro fertilization program.
AB  - OBJECTIVE: To determine whether pituitary down-regulation after gonadotropin
      releasing hormone analogue (GnRH-a) administration can be accurately predicted by
      transvaginal ultrasonographic measurement of endometrial thickness. DESIGN:
      Prospective study. SETTING: An IVF unit of an academic medical center.
      PATIENT(S): One hundred eighty-one patients undergoing 265 IVF-ET treatment
      cycles using GnRH-a in the long protocol. MAIN OUTCOME MEASURE(S): Serum
      concentrations of E2 were determined, and endometrial thickness was measured by
      transvaginal sonography. The accuracy of endometrial thickness for predicting
      pituitary down-regulation was calculated. RESULT(S): Pituitary down-regulation,
      defined as a serum E2 concentration of < or = 55 pg/mL, was achieved in 77% (204
      of 265) of the cycles. An endometrial thickness of < or = 6 mm was found in 92.2%
      (188 of 204) of cycles in which down-regulation was achieved. An estradiol level
      of < or = 55 pg/mL was present in 95.9% (188 of 196) of cycles with endometrial
      thickness of < or = 6 mm. CONCLUSION(S): A state of relative hypoestrogenism
      after GnRH-a administration, indicative of pituitary down-regulation, can be
      predicted with a high degree of accuracy by ultrasonographic measurement of
      endometrial thickness. Thus, routine testing for serum E2 concentration may be
      safely omitted. This may allow further simplification of IVF protocols and
      increase both cost-effectiveness and patients' convenience.

PMID- 9531884
TI  - Microsurgical tubal anastomoses performed as an outpatient procedure by
      minilaparotomy are less expensive and as safe as those performed as an inpatient
      procedure.
AB  - OBJECTIVE: To determine the cost-effectiveness, safety, and success of
      microsurgical tubal anastomoses performed by minilaparotomy as an outpatient.
      DESIGN: Retrospective. SETTING: Military tertiary care medical center.
      PATIENT(S): Seventy consecutively seen women of reproductive age who were
      undergoing surgical reversal of sterilization from August 1, 1993, through August
      1, 1995. INTERVENTION(S): Microsurgical sterilization reversal by minilaparotomy
      was performed as an inpatient (group 1, 47 patients) or as an outpatient (group
      2, 23 patients). MAIN OUTCOME MEASURE(S): Cost, complication rate, pregnancy
      rate. RESULT(S): The procedure cost more for inpatients ($3,116) than for
      outpatients (!,456). Pregnancy rates were similar (56% in group 1 vs. 75% in
      group 2). There was only one complication in the series. CONCLUSION(S):
      Outpatient microsurgical sterilization reversal performed by minilaparotomy is as
      safe and effective as the inpatient procedure and is less expensive.

PMID- 9531886
TI  - Relation of luteinizing hormone levels to body mass index in premenopausal women.
AB  - OBJECTIVE: To assess the relationship between body mass index (BMI) and basal LH
      and the LH-FSH ratio in normally menstruating women. DESIGN: Cross-sectional
      analysis. SETTING: A teaching hospital clinic. PATIENT(S): Premenopausal women
      without cancer, not currently using oral contraceptives, selected from a familial
      ovarian cancer clinic or the general population. INTERVENTION(S): None. MAIN
      OUTCOME MEASURE(S): Early follicular phase plasma LH and FSH. RESULT(S):
      Luteinizing hormone increased slightly and nonsignificantly (P = 0.44) from the
      first to the second quintile of BMI and decreased over all subsequent quintiles.
      Women in the highest quintile of BMI (> 27.1) had significantly lower LH levels
      than women in the lowest quintile of BMI (< or = 20.4; P = 0.003). Compared with
      women in the second quintile of BMI who had the highest LH levels, women in the
      highest quintile of BMI had LH levels that were 40% lower. The relationship
      between BMI and the LH-FSH ratio was similar, though not as strong.
      CONCLUSION(S): Over most of the range of BMIs observed in this study, BMI was
      inversely associated with LH. These results suggest that the upper limits of
      normal for LH may need to be shifted downward for heavier women.

PMID- 9531887
TI  - Use of the antral follicle count to predict the outcome of assisted reproductive
      technologies.
AB  - OBJECTIVE: To evaluate the predictive value of the antral follicle count in
      patients undergoing assisted reproductive technologies (ARTs). DESIGN:
      Prospective study. SETTING: Tertiary care institutional hospital. PATIENT(S):
      Consecutively seen patients undergoing ARTs such as IVF-ET, gamete intrafallopian
      transfer, and tubal embryo transfer (TET). INTERVENTION(S): The ovarian antral
      follicle number was determined by transvaginal ultrasonography on the first or
      second menstrual day, before the administration of gonadotropins, in patients
      undergoing ARTs. MAIN OUTCOME MEASURE(S): Ovulation induction was accomplished
      with the use of GnRH agonist down-regulation combined with FSH and menotropin
      stimulation. Gamete intrafallopian transfer or TET was performed in patients with
      patent fallopian tubes, and IVF-ET was undertaken in the remaining patients.
      Analysis of variance and Mantel-Haenszel monotonic test for trends were used for
      data analysis. RESULT(S): A total of 149 treatment cycles for 130 couples were
      performed during the study period. The procedures performed included 89 ETs, 26
      gamete intrafallopian transfers, 13 TET cycles, and 21 incomplete cycles (9 poor
      responders, 6 failed retrievals, and 6 nonfertilization cycles). All treatment
      cycles were divided into three groups according to the number of antral follicles
      (i.e., < or = 3, 4-10, and > or = 11) to evaluate the influence of various
      factors. The antral follicle count correlated significantly with patient age, day
      3 serum FSH level, use of gonadotropins, serum estradiol concentration, number of
      oocytes retrieved, and, later, number of oocytes or embryos transferred. The
      group of patients who had a lower antral follicle count also had a significantly
      higher rate of cycle cancellation compared with the other two groups (68.8% vs.
      5.3% and 0, respectively). No pregnancies occurred in the low antral follicle
      count group, whereas there was a trend toward an increasing number of pregnancies
      per attempt as the number of antral follicles increased (0, 23.7%, and 36.8%,
      respectively). CONCLUSION(S): It is easy to determine the number of antral
      follicles with a diameter of 2-5 mm on the first or second day of menstruation,
      or just before the administration of exogenous gonadotropins. We were able to
      predict the ovarian response and pregnancy results of patients undergoing ARTs
      with the use of this simple procedure.

PMID- 9531888
TI  - Pelvic adhesions contain sex steroid receptors and produce angiogenesis growth
      factors.
AB  - OBJECTIVE: To evaluate female pelvic adhesion tissue for the presence of estrogen
      receptor (ER), progesterone receptor (PR), basic fibroblastic growth factor
      (basic-FGF), and vascular endothelial growth factor (VEGF). DESIGN: Descriptive
      study. SETTING: Patients at a tertiary medical center. PATIENTS: Female
      reproductive age patients undergoing gynecologic surgery who were not receiving
      hormonal therapy. INTERVENTIONS: Female reproductive tract peritoneal adhesion
      tissue was excised, frozen, and sent for immunohistologic evaluation. MAIN
      OUTCOME MEASURE: Presence of ER, PR, basic-FGF, and VEGF in adhesion tissue.
      RESULTS: Nineteen of 19 specimens were positive for PR; 16 of 19 specimens were
      positive for ER, which was present in a variety of the different cell types
      constituting adhesion. Vascular endothelial growth factor and basic-FGF were
      detected in endothelial cells of blood vessels supplying this tissue as well as
      in mesothelial cells. CONCLUSION: Adhesion tissue contains ER, PR, and growth
      factors that may be important in the genesis of the permanent fibrovascular bands
      between pelvic organs. This supports the theoretical possibility of hormonal
      manipulation of these tissues to negatively influence postoperative pelvic
      adhesion formation.

PMID- 9531889
TI  - Antisperm antibody treatment mode: levels of antisperm antibodies after
      incubation with TEST-yolk buffer and filtration using the SpermPrep II method.
AB  - OBJECTIVE: To assess whether incubation in TEST-yolk buffer (TYB) or human tubal
      fluid (HTF) could alter the sperm membrane characteristics and its relationship
      to antisperm antibodies (ASA) and/or antigen detachment from the sperm membrane
      and to evaluate the filtration of those specimens and possible recovery of ASA
      free spermatozoa. DESIGN: A prospective clinical study. SETTING: Andrology
      Institute of Lexington, Lexington, Kentucky. PATIENT(S): Twenty patients
      undergoing infertility treatment. MAIN OUTCOME MEASURE(S): Recovery of
      spermatozoa with reduced levels or antisperm antibody-free sperm after treatment
      with TYB or HTF, followed by filtration using the SpermPrepII method (Sephadex
      based). RESULT(S): Assessment of ASA using the direct immunobead test showed no
      significant differences between specimens incubated for 2 hours in seminal plasma
      (fresh) or HTF with regard to levels of IgA and IgG. The percentage binding of
      anti-IgA and anti-IgG immunobeads was significantly reduced in specimens
      incubated for 2 hours in TYB compared with specimens incubated in seminal plasma
      or HTF. Furthermore, selection of spermatozoa using the SpermPrepII filtration
      method significantly reduced the percentage binding of anti-IgA and anti-IgG
      immunobeads compared with specimens incubated in HTF. CONCLUSION(S): The results
      suggest that TYB either altered the sperm membrane properties so that there was a
      decreased affinity at the antibody and/or antigen sites or that the egg yolk
      proteins were absorbing the antibodies and/or antigens complexes from the sperm
      membrane surface. Incubation of spermatozoa in TYB followed by filtration with
      the SpermPrepII method improved the recovery of ASA-free spermatozoa by
      selectively entrapping spermatozoa with ASA bound to its surface.

PMID- 9531890
TI  - Effects of low concentrations of nitric oxide on the zona pellucida binding
      ability of human spermatozoa.
AB  - OBJECTIVE: To investigate the direct effects of sodium nitroprusside, a nitric
      oxide donor, on the fertilizing ability of human spermatozoa in vitro. DESIGN:
      Prospective, controlled in vitro study. SETTING: IVF Unit, Medical College
      Hospital. PATIENT(S): Women undergoing conventional IVF. INTERVENTION(S): Human
      spermatozoa samples were incubated with a nitric oxide donor and a nitric oxide
      quencher, carboxy-imidazolineoxyl N-oxides. MAIN OUTCOME MEASURE(S): The
      capacitation and the acrosome reaction rates were determined by chlortetracycline
      assay. Sperm zona pellucida binding and sperm penetration into oocytes were
      determined using the hemizona assay and the human aged zona-free oocyte sperm
      penetration assay. RESULT(S): High concentrations of sodium nitroprusside (10(-3)
      and 10(-5) M) inhibited sperm motility and viability. In contrast, low
      concentrations of sodium nitroprusside (10(-7) and 10(-8) M) did not affect
      motility and resulted in increased capacitation (47 +/- 6% at 10(-7) M, 42 +/- 6%
      at 10(-8) M, and 24 +/- 4% in controls, respectively, P < 0.01). A twofold
      increase in the hemizona index occurred compared to the matched control. However,
      low levels of sodium nitroprusside treatment did not affect the acrosome reaction
      and human zona-free oocyte sperm penetration rates. CONCLUSION(S): Low
      concentrations of nitric oxide may have some physiologic role in fertilization
      through the enhancement of capacitation and zona pellucida binding but not by the
      induction of the acrosome reaction or the facilitation of penetration into
      oocytes.

PMID- 9531891
TI  - Sperm deoxyribonucleic acid fragmentation is increased in poor-quality semen
      samples and correlates with failed fertilization in intracytoplasmic sperm
      injection.
AB  - OBJECTIVE: To determine the incidence of DNA fragmentation in human sperm used
      for intracytoplasmic sperm injection (ICSI) and to correlate any detected DNA
      damage with semen analysis parameters and fertilization rates in ICSI. DESIGN:
      Descriptive and correlational clinical study. SETTING: Tertiary care fertility
      clinic. PATIENT(S): A total of 150 semen samples was collected from men in the
      ICSI program. INTERVENTION(S): For each sample, sperm wash and swim-up were
      performed, and the percentage of recovered sperm with DNA fragmentation was
      determined with the use of terminal transferase-mediated deoxyuridine
      triphosphate-biotin end labeling. MAIN OUTCOME MEASURE(S): The percentage of
      sperm with DNA fragmentation was correlated with semen analysis parameters and
      ICSI fertilization rates. RESULTS(S): The mean (+/- SD) percentage of sperm with
      fragmented DNA was 14.5% +/- 1.5% and ranged from 0.5% to 75%. A significant
      negative association was found between the percentage of sperm with DNA
      fragmentation and the ICSI fertilization rate. We also observed that the motility
      and morphology of the ejaculated sperm were correlated negatively with the
      percentage of DNA fragmentation in the washed sperm recovered by the swim-up
      technique. CONCLUSION(S): Our results suggest that when poor-quality semen
      samples are used for ICSI, there is a greater likelihood that some sperm selected
      for injection, despite appearing normal, contain fragmented DNA. Whether sperm
      DNA damage may contribute to failure of pronuclear formation and embryo
      development in some apparently unfertilized ICSI oocytes is unclear.

PMID- 9531892
TI  - Absence of cyclic adenosine 3':5' monophosphate responsive element modulator
      expression at the spermatocyte arrest stage.
AB  - OBJECTIVE: To test the hypotheses that variations in the expression of adenosine
      3':5' monophosphate (cAMP) responsive element modulator are found in human
      seminiferous epithelium in men with impaired testicular function and subsequent
      infertility and that variations in apoptosis frequency are associated with
      differential cAMP responsive element modulator expression in male infertility
      states. DESIGN: Standard immunohistochemical staining using a rabbit polyclonal
      antibody against the tau isoform of the cAMP responsive element modulator protein
      was performed on 5-microM sections of Bouin's fixed, paraffin-embedded testicular
      tissue obtained from azoospermic or severely oligozoospermic men for routine
      clinical purposes. Histologic diagnosis was confirmed with computerized image
      analysis of Feulgen-stained sections. SETTING: Tertiary male infertility referral
      center at a medical school. PATIENT(S): Forty-eight testis biopsies were
      performed in 38 azoospermic or severely oligozoospermic males. INTERVENTION(S):
      Rabbit polyclonal cAMP responsive element modulator tau antibody was applied to
      the paraffin-embedded testis sections. MAIN OUTCOME MEASURE(S): Testis
      immunoreactivity to polyclonal cAMP responsive element modulator tau antibody and
      apoptotic indices. RESULT(S): Although cAMP responsive element modulator
      immunoreactivity was present in the round spermatid stage of meiosis in testis
      biopsy specimens showing normal spermatogenesis, spermatid maturation arrest, and
      hypospermatogenesis, there was complete absence of expression in biopsy specimens
      from patients with Sertoli cell only and spermatocyte maturation arrest states.
      In addition, significantly increased apoptotic indices were observed in the
      spermatocyte maturation arrest state in comparison with normal spermatogenesis
      and Sertoli cell only pattern. CONCLUSION(S): These data suggest that cAMP
      responsive element modulator may be important for spermatid development and a
      stage-specific regulator of human spermatogenesis. Absence of cAMP responsive
      element modulator may be a cause of testicular failure in various types of male
      infertility.

PMID- 9531893
TI  - Laser-assisted microdissection of the zona pellucida facilitates polar body
      biopsy.
AB  - OBJECTIVE: To investigate whether polar body biopsy can be performed after laser
      microdissection of the zona pellucida (ZP). DESIGN: Mouse zygotes were allocated
      randomly to three groups. The zygotes were subjected to laser microdissection of
      the ZP and polar body biopsy (group 1), laser microdissection alone (group 2), or
      no treatment (group 3). SETTING: University-based IVF program. PATIENT(S): Animal
      study. INTERVENTION(S): A hole was drilled in the ZP of mouse zygotes using a
      1.48-micron noncontact diode laser. A microneedle was inserted and the polar body
      was aspirated. MAIN OUTCOME MEASURE(S): The efficacy of polar body biopsy after
      laser microdissection of the ZP was evaluated. RESULT(S): The laser diode beam
      allowed for precise drilling of a 14- to 18-micron hole in the ZP. Polar bodies
      could be aspirated without damaging the zygote and did not disintegrate during
      the biopsy. Zygotes developed to blastocysts and underwent the same hatching as
      control zygotes. Lower hatching rates were observed in untreated zygotes.
      CONCLUSION(S): Laser microdissection of the ZP with a noncontact laser system
      facilitates subsequent polar body biopsy. The use of blunt-ended micropipettes
      greatly reduces the risk of damage to the zygote or the polar body. This
      procedure makes polar body biopsy more accurate and effective for preimplantation
      genetic diagnosis.

PMID- 9531894
TI  - Generation and characterization of a polyclonal antipeptide antibody to human
      glycodelin.
AB  - OBJECTIVE: To develop and characterize an antiglycodelin antibody using a 15
      amino acid synthetic peptide as antigen, derived from the sequence of human
      glycodelin. DESIGN: We have developed a chicken antiglycodelin-derived peptide
      antibody and have characterized the antibody with the use of endometrial and
      ovarian cell lines. The antibody was also tested for its ability to detect
      glycodelin by ELISA assay, immunocytochemistry, and by Western blot. SETTING:
      Various cell lines, cell culture medium, and amniotic fluid were used in the
      experiments. PATIENT(S): Amniotic fluid was collected from pregnant patients in
      their first trimester of pregnancy. INTERVENTION(S): No intervention. MAIN
      OUTCOME MEASURE(S): Detection of glycodelin. RESULT(S): The cell lines RL95-2
      (human endometrial carcinoma cells), OVCAR-3 (human ovarian adenocarcinoma
      cells), HeLa (human cervical epitheloid carcinoma cells), and EM42-D (human
      endometrial epithelial cells) reacted with the antibody, indicating the presence
      of glycodelin. A specific 45-kd protein representing glycodelin was detected by
      Western blot in the amniotic fluid. CONCLUSION(S): Antipeptide antibodies can be
      successfully used to detect and quantify the presence of glycodelin in cells and
      fluids.

PMID- 9531895
TI  - Atraumatic cervical passage at outpatient hysteroscopy.
AB  - OBJECTIVE: To evaluate the efficacy of topical anesthesia routinely administered
      to reduce discomfort and the need for additional local anesthesia during
      outpatient hysteroscopy. DESIGN: Comparative observational study. SETTING:
      Outpatient hysteroscopy clinic in a University hospital. PATIENT(S): Three
      hundred patients undergoing outpatient hysteroscopy. INTERVENTION(S): Application
      of lidocaine spray both to the surface of the cervix and into the cervical canal
      before performing hysteroscopy. MAIN OUTCOME MEASURE(S): The discomfort during
      passage of the hysteroscope through the cervical canal, the need for additional
      local anesthesia, and the failure rate of outpatient hysteroscopy. RESULT(S): One
      hundred fifty consecutive patients receiving lidocaine spray before the
      hysteroscopy were compared to a control group of another 150 consecutive patients
      who underwent the examination without pretreatment. Women treated with spray
      experienced significantly less pain at insertion of the hysteroscope.
      Furthermore, the spray significantly reduced both the need for additional
      anesthesia and the rate of failed hysteroscopies due to intolerable pain.
      CONCLUSION(S): Topical anesthesia with lidocaine spray is a simple method to
      alleviate patients' discomfort during cervical passage. It is effective in
      reducing the need for local anesthesia and should reduce the rate of failed
      outpatient hysteroscopies.

PMID- 9531896
TI  - Comparison of carbon dioxide and air pneumoperitoneum for gamete intrafallopian
      transfer under conscious sedation and local anesthesia.
AB  - OBJECTIVE: To compare patient tolerance and pregnancy rates (PRs) between two
      cohorts that underwent GIFT under local anesthesia with air versus carbon dioxide
      (CO2) pneumoperitoneum. DESIGN: Retrospective study. SETTING: University clinic.
      PATIENT(S): Eighty-five patients who underwent 125 laparoscopies under conscious
      sedation for GIFT using air pneumoperitoneum were compared with 42 patients who
      had 70 GIFT procedures with CO2 pneumoperitoneum. INTERVENTION(S): Transvaginal
      ultrasound-guided egg retrieval followed by GIFT with compressed air or CO2 for
      pneumoperitoneum under local anesthesia and i.v. sedation. MAIN OUTCOME
      MEASURE(S): Patient tolerance and viable PR. RESULT(S): The percentage of
      patients scoring "very good" was lower in the CO2 group (73% for air versus 57%
      for CO2), but the combined percentage of those scoring "very good" or "good" was
      comparable at 89% and 87%. The difference in the viable PRs between the two
      groups (43% versus 37%) for patients < 40 years old was not statistically
      significant. CONCLUSION(S): Patient tolerance and PRs are similar for air and CO2
      pneumoperitoneum during GIFT under local anesthesia. Given the theoretical risk
      of air embolus and lack of detrimental effect of CO2 on patient tolerance and
      success rate, it seems prudent to use CO2 in such a setting.

PMID- 9531897
TI  - Pregnancy after human donor oocyte cryopreservation and thawing in association
      with intracytoplasmic sperm injection in a patient with ovarian failure.
AB  - OBJECTIVE: To describe a pregnancy after human donor oocyte cryopreservation in
      association with intracytoplasmic sperm injection in a patient with ovarian
      failure. SETTING: Department of Reproductive Medicine, CER Medical Institute,
      Buenos Aires, Argentina. PATIENT: A 48-year-old patient with ovarian failure.
      RESULTS: Ten donated oocytes were cryopreserved. Survival after thawing was 30%.
      Three oocytes were microinjected, and two embryos were obtained. The
      fertilization rate was 66%, and embryo development was 100%. Both embryos were
      transferred to a patient who had received hormonal replacement therapy. The
      attempt was successful, and a pregnancy was achieved after the transfer.
      CONCLUSION: In association with intracytoplasmic sperm injection, an adequate
      technique of freezing and thawing of human oocytes might achieve encouraging
      results in ART programs.

PMID- 9531898
TI  - Recurrent in vitro fertilization failure evaluated by fluorescence in situ
      hybridization: a case report.
AB  - OBJECTIVE: To present a case of IVF failure evaluated by fluorescence in situ
      hybridization (FISH). DESIGN: Case report. SETTING: Research university
      laboratory and clinical IVF laboratory. PATIENT(S): An infertile couple with
      recurrent IVF failure. INTERVENTION(S): Fluorescence in situ hybridization study
      of the complete cohort of "zygotes" obtained at the third IVF attempt. MAIN
      OUTCOME MEASURE(S): Fluorescence in situ hybridization studies of chromosomes X,
      Y, 13, 18, and 21. RESULT(S): All the recovered putative zygotes were abnormal
      for the expected ploidy, presumably as a result of abnormal oocytes.
      CONCLUSION(S): Fluorescence in situ hybridization techniques represent a
      promising approach to analyze zygotes that fail to divide normally in vitro and
      eggs that fail to become fertilized. In cases of recurrent IVF failure, the
      results of FISH could be used to counsel couples and thus to help them choose
      among methods other than IVF for assisted reproduction.

PMID- 9531899
TI  - Electroejaculation in combination with intracytoplasmic sperm injection in
      patients with psychogenic anejaculation results in lower fertilization rates.
AB  - OBJECTIVE: To evaluate the outcome of intracytoplasmic sperm injection (ICSI)
      with sperm obtained by electroejaculation in men with psychogenic anejaculation.
      DESIGN: Retrospective clinical study. SETTING: In Vitro Fertilization Unit, Bikur
      Cholim Hospital, Jerusalem, Israel. PATIENT(S): Seven men with psychogenic
      anejaculation who underwent 16 sessions of electroejaculation in combination with
      ICSI. INTERVENTION(S): Electroejaculation, ICSI. MAIN OUTCOME MEASURE(S): Semen
      analysis, ICSI, fertilization rates. RESULT(S): All patients had poor sperm
      motility. One hundred forty-seven oocytes were injected, with a fertilization
      rate of 27% (39/142). One ongoing pregnancy was achieved. CONCLUSION(S): Sperm
      obtained by electroejaculation have low motility and reduced fertilization
      potential. Nevertheless, ICSI should be offered to improve the possibility of
      successful pregnancy.

PMID- 9531900
TI  - Sperm morphology evaluated by computer (IVOS) cannot predict the fertilization
      rate in vitro after intracytoplasmic sperm injection.
AB  - OBJECTIVE: To evaluate sperm morphology assessment using the IVOS (Hamilton
      Thorne Research Version 3 Dimension Program, Beverly, MA) system in prediction of
      fertilization rate in vitro after intracytoplasmic sperm injection (ICSI).
      DESIGN: A prospective clinical study. SETTING: Diagnostic andrology laboratory
      and assisted conception service. PATIENT(S): Thirty-five patients from the ICSI
      program were evaluated. Semen samples were analyzed using a computerized system
      for conventional semen parameters, sperm movement characteristics, and sperm
      morphology. Only patients with three or more metaphase II (MII) oocytes available
      were studied. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Fertilization rates
      in vitro after ICSI were compared according to the sperm morphology obtained from
      the IVOS system. RESULT(S): Linear regression analysis of fertilization rates
      against the sperm parameters assessed by computer (IVOS), which included
      conventional semen parameters, sperm movement characteristics, percentage of
      normal sperm morphology, and percentage of each specific abnormal sperm
      morphology, did not reveal any significant correlations. The mean (+/- SEM)
      fertilization rates in the healthy prognosis group (normal sperm morphology > or
      = 4%) and poor prognosis group (normal sperm morphology < or = 4%) were 82.4 +/-
      4.0% and 75.0 +/- 3.8%, respectively. There was no statistically significant
      difference in the mean fertilization rate between both groups. Moreover, no
      statistically significant difference was found in overall fertilization rates in
      vitro between the two prognosis categories (79.6% versus 78.0%). CONCLUSION(S):
      Sperm morphology obtained from the IVOS system is not related to the outcome of
      ICSI and cannot be used for prediction of fertilization rate in vitro after ICSI.

PMID- 9531901
TI  - The simplified two-pipette technique is more efficient than the conventional
      three-pipette method for blastomere biopsy in human embryos.
AB  - OBJECTIVE: To evaluate the efficiency and efficacy of a simplified two-pipette
      technique in comparison to the conventional three-pipette method; in the two
      pipette method, a single, larger drilling/biopsy pipette is used to perform zona
      pellucida (ZP) drilling and blastomere aspiration for embryo biopsy. DESIGN: A
      preclinical, prospective, randomized, in vitro experiment. SETTING: The
      reproductive unit of a university teaching hospital. PATIENT(S): Ninety-five
      excess embryos at the two- to four-cell stage were obtained from 35 patients
      undergoing IVF. INTERVENTION(S): At the six- to eight-cell stage, 88 embryos were
      allocated randomly to three groups: group I for the conventional method (n = 29),
      group II for the simplified technique (n = 30), and group III for controls (n =
      29). The embryos then were cultured in vitro. The retrieved blastomeres were
      fixed and examined with fluorescence in situ hybridization using X and Y probes
      simultaneously. MAIN OUTCOME MEASURE(S): Biopsy time, successful retrieval of a
      blastomere, fixation of the cell, signals developed from fluorescence in situ
      hybridization, and growth potential and hatching capacity of the biopsied embryos
      were evaluated. RESULT(S): The mean time (+/- SD) for biopsy of each embryo in
      group I (435 +/- 137 seconds) was significantly longer than that in group II (126
      +/- 32 seconds). The success rates for obtaining an intact blastomere were not
      different between group I (93%) and group II (97%). The growth capacity to the
      blastocyst stage was similar among the three groups (34%, 37%, and 38%,
      respectively). However, the ZP-drilled and biopsied embryos of groups I and II
      had higher percentages of hatching (34% and 37%, respectively) and complete
      hatching (17% and 20%, respectively) than did those of group III (10% and 0,
      respectively). The blastomeres obtained by biopsy in groups I and II were equally
      fixed (90% vs. 90%, respectively) and shown in fluorescence in situ hybridization
      (79% vs. 80%, respectively). CONCLUSION(S): Compared with the conventional
      method, the simplified technique is more efficient and equally efficacious for
      blastomere biopsy in preimplantation genetic diagnosis.

PMID- 9531902
TI  - Prolactin producing pituitary tumors in postmenopausal patients--"infrequent or
      infrequently recognized".

PMID- 9531903
TI  - Sperm factors and spontaneous abortion after IVF.

PMID- 9531905
TI  - Family physicians and the tuberculosis epidemic.

PMID- 9531904
TI  - Management of bacterial vaginosis during pregnancy.

PMID- 9531906
TI  - A pulseless hand: accidental epinephrine injection.

PMID- 9531907
TI  - Reducing complications in type 2 diabetes.

PMID- 9531908
TI  - Antibiotic therapy and serum digoxin toxicity.

PMID- 9531909
TI  - Cultural aspects of caring for refugees.

PMID- 9531910
TI  - Acute bronchitis.
AB  - Acute bronchitis is a lower respiratory tract infection that causes reversible
      bronchial inflammation. In up to 95 percent of cases, the cause, is viral. While
      antibiotics are often prescribed for patients with acute bronchitis, little
      evidence shows that these agents provide significant symptomatic relief or
      shorten the course of the illness. In a few small studies, bronchodilators such
      as albuterol have been found to relieve some symptoms of acute bronchitis.
      Increased attention is being given to the role of Chlamydia species in acute
      bronchitis and adult-onset asthma. Studies in progress may help to clarify the
      importance of these organisms in acute bronchitis and to determine whether early
      treatment can prevent or ameliorate asthma.

PMID- 9531911
TI  - Bacterial vaginosis: an update.
AB  - Bacterial vaginosis is the most common cause of vaginal discharge. Recent studies
      have confirmed its association with pelvic inflammatory disease and adverse
      pregnancy outcomes. Bacterial vaginosis is treated with oral metronidazole (given
      either as a single dose or a seven-day course) or clindamycin. Treatment with
      topical clindamycin or metronidazole is also effective in returning the vaginal
      flora to normal but may be less effective in preventing the increased incidence
      of adverse pregnancy outcomes.

PMID- 9531912
TI  - Osteopetrosis.
AB  - Osteopetrosis is a rare hereditary bone disorder that presents in one of three
      forms: osteopetrosis tarda, osteopetrosis congenita and "marble bone" disease.
      Osteopetrosis tarda, the benign form, presents in adulthood, while the two more
      malignant variants, osteopetrosis congenita and marble bone disease, present in
      infancy and childhood, respectively. In all three forms, the main features are
      pathologic alteration of osteoclastic bone resorption and thickening of cortical
      and lamellar bones. Osteopetrosis tarda is usually discovered accidentally on
      routine radiographs and is often asymptomatic; however, patients may present
      because of related degenerative joint disease. Osteopetrosis congenita results in
      bone marrow failure and is almost always fatal. Marble bone disease causes short
      stature, cerebral calcification and mental retardation. Bone marrow transplant is
      the only chance for survival in patients with osteopetrosis congenita.

PMID- 9531913
TI  - Dietary therapy for preventing and treating coronary artery disease.
AB  - Nearly one half of Americans die of cardiovascular disease. The morbidity and
      mortality associated with coronary artery disease is strongly related to abnormal
      lipid levels, oxidation of lipids and intra-arterial clot formation. Nutrition
      powerfully influences each of these factors. There is growing evidence that
      patients can improve lipid levels and decrease the rate of cardiovascular events
      by "adding" specific foods to their diets and switching from saturated and
      polyunsaturated to monounsaturated fats and n-3 fatty acids. Appropriate dietary
      changes decrease arteriosclerotic plaque formation, improve endothelial vasomotor
      dynamics, reduce oxidation of low-density lipoproteins and enhance thrombolytic
      activity. Brief discussions between physicians and patients can influence
      patients' food choices. Changes in diet can reduce the premature mortality and
      morbidity associated with coronary artery disease.

PMID- 9531914
TI  - Pitfalls in the radiologic evaluation of extremity trauma: Part II. The lower
      extremity.
AB  - Fractures of the lower extremity are common reasons for visits to family
      physicians. Some lower extremity fractures are especially likely to be missed.
      Examples of lesions that commonly go unrecognized include sacral insufficiency or
      fatigue fracture, fracture of the femoral neck (especially if the fracture is
      nondisplaced and/or impacted), tibial plateau fracture, Segond fracture (vertical
      fracture of the lateral tibia), patellar fracture, calcaneal fracture of the
      foot, Lisfranc fracture/dislocation of the tarsometatarsal apparatus, and Jones
      fracture of the fifth metatarsal. Lower extremity fracture in children may
      suggest the possibility of child abuse, especially in the case of multiple or
      bilateral fractures.

PMID- 9531915
TI  - Diabetic foot ulcers: prevention, diagnosis and classification.
AB  - Diabetic ulcers are the most common foot injuries leading to lower extremity
      amputation. Family physicians have a pivotal role in the prevention or early
      diagnosis of diabetic foot complications. Management of the diabetic foot
      requires a thorough knowledge of the major risk factors for amputation, frequent
      routine evaluation and meticulous preventive maintenance. The most common risk
      factors for ulcer formation include diabetic neuropathy, structural foot
      deformity and peripheral arterial occlusive disease. A careful physical
      examination, buttressed by monofilament testing for neuropathy and noninvasive
      testing for arterial insufficiency, can identify patients at risk for foot ulcers
      and appropriately classify patients who already have ulcers or other diabetic
      foot complications. Patient education regarding foot hygiene, nail care and
      proper footwear is crucial to reducing the risk of an injury that can lead to
      ulcer formation. Adherence to a systematic regimen of diagnosis and
      classification can improve communication between family physicians and diabetes
      subspecialists and facilitate appropriate treatment of complications. This team
      approach may ultimately lead to a reduction in lower extremity amputations
      related to diabetes.

PMID- 9531916
TI  - Seasonal affective disorders.
AB  - Seasonal affective disorder is a pattern of major depressive episodes that occur
      and remit with changes in seasons. It may be seen in major depressive or bipolar
      disorders, as described in the Diagnostic and Statistical. Manual of Mental
      Disorders (DSM-IV). The most recognized form of seasonal affective disorder,
      "winter depression," is characterized by recurrent episodes of depression,
      hypersomnia, augmented appetite with carbohydrate craving, and weight gain that
      begin in the autumn and continue through the winter months. Physicians have many
      options for treating seasonal affective disorder. While questions regarding the
      validity of seasonal affective disorder as a syndrome and the mechanism of action
      of light therapy continue to be investigated, the established effectiveness of
      light therapy in patients with winter depression supports the usefulness of
      assessment for this seasonal pattern and consideration of light therapy as an
      option in addition to existing treatment choices.

PMID- 9531918
TI  - ACIP releases recommendations for the immunization of health care workers.

PMID- 9531917
TI  - Diagnostic approach to the confused elderly patient.
AB  - Confusion in the elderly patient is usually a symptom of delirium or dementia,
      but it may also occur in major depression and psychoses. Until another cause is
      identified, the confused patient should be assumed to have delirium, which is
      often reversible with treatment of the underlying disorder. Causes of delirium
      include metabolic disorders, infections and medications. Thyroid dysfunction,
      vitamin deficiencies and normal-pressure hydrocephalus are some potentially
      reversible causes of dementia. Major irreversible causes include Alzheimer's
      disease, central nervous system damage and human immunodeficiency virus
      infection. All but the rarest causes of confusion can usually be identified based
      on the complete history, medication review, physical examination, mental status
      evaluation and laboratory evaluation with longitudinal reevaluation.

PMID- 9531919
TI  - Consensus statement focuses on diagnosis and treatment of Alzheimer's disease and
      related disorders in primary care.

PMID- 9531920
TI  - [Irbesartan--current trends in the management of hypertension].

PMID- 9531921
TI  - [To diagnose and treat sinusitis. 8th Congress of the Society for Phytotherapy.
      Symposium: "Phytotherapy in Sinusitis". Wurzburg 27 November 1997].

PMID- 9531922
TI  - Pulmonary diseases in women.
AB  - Pulmonary disease has tremendous impact on both men and women. Fortunately, we
      have the capacity to prevent a significant percentage of disease with appropriate
      education for physicians and patients. The majority of the article on pulmonary
      diseases in women will address smoking and its impact on women's health, as well
      as smoking cessation. Pulmonary diseases that effect women particularly will be
      addressed as well.

PMID- 9531923
TI  - Breast disease.
AB  - This article reviews the presentation and management of common breast disorders.
      It focuses on the diagnosis of treatment and management of patients with breast
      cancer in a multidisciplinary approach.

PMID- 9531925
TI  - Medical problems during pregnancy.
AB  - Dramatic physiologic changes are part of normal human pregnancy. The physiologic
      alterations of pregnancy have the potential to affect chronic diseases, to unmask
      subclinical conditions, or to alter the presentation and course of newly acquired
      illnesses. An update in selected topics of obstetric medicine follows, focusing
      on clinical entities in which there have been significant advances in diagnosis
      or management. Additionally, reviews of selected medical disorders, such as HIV
      infection and asthma, that are rising in incidence in women of reproductive age
      are included.

PMID- 9531924
TI  - Gynecologic health and disease.
AB  - Traditionally the obstetrician/gynecologist has been the sole provider of health
      care for women. As the United States moves toward a system of greater managed
      care, however, family practitioners, internists, and other physician extenders
      (physician assistants, nurse-practitioners, and nurse-midwives) are the first
      line providers for many women. These practitioners have the opportunity to
      influence behavioral changes and promote healthy habits by identifying risk
      factors and their potential consequences.

PMID- 9531926
TI  - Infertility. A clinical guide for the internist.
AB  - Infertility is a common condition that internists practicing primary care may
      increasingly encounter. Abnormal male semen parameters, ovulation disorders, and
      tubal dysfunction account for most cases of infertility. By performing a complete
      initial evaluation and through appropriate and timely referral, internists can
      contribute to the care and improve outcomes for couples with this condition
      (Table 9).

PMID- 9531927
TI  - Menopause and hormone replacement therapy.
AB  - Menopause is a normal part of life of most women and can be made easier with
      appropriate information about the events that occur. For those women who desire
      help for bothersome menopausal symptoms, effective therapy can be offered. The
      use of HRT for prevention is more complex. Several large randomized clinical
      trials, including the Women's Health Initiative (WHI) and the Heart and Estrogen
      Replacement Therapy Study (HERS) in the United States, are currently underway.
      These trials, which have as end points clinical events such as myocardial
      infarction, sudden death, fractures, and cancer, will provide answers to many of
      the questions raised in this discussion. Until the results of these trials are
      available, clinicians must be prudent in their recommendations and should keep
      their patients apprised of the relevant uncertainties of preventive HRT.

PMID- 9531928
TI  - Cancer and women.
AB  - Women have special physiologic considerations that may increase their risk of
      being diagnosed with certain cancers; however, the most important aspect to
      remember is that women are diagnosed with and die from many of the same
      malignancies as men. Health care providers need to be vigilant in evaluating
      women because one of the best ways to increase the chance of survival is early
      detection.

PMID- 9531929
TI  - HIV disease and women.
AB  - Women with HIV disease are at risk for the same complications as men as their
      disease progresses. Women, however require some special considerations. This
      article will elucidate the epidemiology, disease transmission, gynecologic
      complications, pregnancy, and evaluation of the HIV infected women.

PMID- 9531930
TI  - Women's mental health in primary care. Depression, anxiety, somatization, eating
      disorders, and substance abuse.
AB  - Primary care physicians can improve the care of women patients by applying new
      concepts of women's physiology and psychosocial development. New developmental
      models that emphasize the importance of relationships in women's self-concept and
      well-being have led to effective psychotherapies for depression, eating
      disorders, anxiety and substance abuse. Many of these therapies can be offered in
      brief formats suitable to primary care settings. New biological treatments
      including the use of estrogen, thyroid hormone and bright light for depression
      and refeeding to increase metabolic rate in eating disorders also promise to
      expand the range of mental health problems that generalist physicians can treat
      successfully.

PMID- 9531931
TI  - Domestic violence in women.
AB  - Domestic violence is a significant public health issue affecting women. Numerous
      medical organizations have recommended that routine screening of women be
      conducted to assist in the prevention, identification, and care for victims of
      violence. This article examines the scope of domestic violence in women, reviews
      ways to recognize abuse, examines the potential impact of abuse upon health and
      discusses the management of victims.

PMID- 9531932
TI  - Immunobiology of renal transplantation.
AB  - The clinical application of our knowledge of the immune barriers to
      transplantation has advanced allo-organ replacement therapy to the level of
      routine practice, while simultaneously engendering a critical shortage in
      available donors. Recent work in xenotransplantation addresses this need. The
      current understanding of the immune barriers to transplantation has evolved to
      consider alternate responses to alloantigen, namely acceptance. The delineation
      and application of recent discoveries in T cell costimulatory events, antigen
      presentation, and differential T lymphocyte responses are opening pathways
      towards the development of tolerogenic protocols for use in clinical
      transplantation. This article presents a review of transplant immunobiology with
      special attention to antigen presentation and T-cell activation as phases of the
      immune response relevant to the discussion of transplant tolerance.

PMID- 9531933
TI  - The evaluation of prospective renal transplant recipients and living donors.
AB  - The evaluation of transplant candidates should be directed to ensuring that the
      risks of surgery and immunosuppression are acceptable. The evaluation should also
      attempt to determine the likelihood of the graft functioning well enough and long
      enough to improve the quality of life of the recipient. The primary goal in the
      evaluation of a potential living donor is to ensure the donor's safety. Both the
      short- and long-term risks of donation need to be carefully assessed.

PMID- 9531934
TI  - Procurement, preservation, and transport of cadaver kidneys.
AB  - This article discusses the guidelines for brain death determination, the criteria
      for donor selection, the management of the cadaveric donor, the surgical
      techniques of isolated renal and multiorgan retrieval, methods of organ
      preservation, and proper transport of organs to the recipient.

PMID- 9531935
TI  - Surgical technique/post-transplant surgical complications.
AB  - Renal transplantation has become a common form of therapy for the patient with
      end-stage renal disease. The operative procedure has been refined and is
      discussed. Fortunately, surgical complications requiring therapy are unusual. An
      overview of the surgical complications, including etiology and therapeutic
      options, is presented.

PMID- 9531936
TI  - Clinical application of immunosuppressive agents in renal transplantation.
AB  - The availability of a number of new immunosuppressive drugs has resulted in
      significant improvements in the outcome of kidney transplantation. Currently 1
      year graft survival rate for cadaver kidney transplants is approximately 85%. A
      number of new agents are presently in clinical studies. This article reviews the
      currently available agents and examines various aspects of induction and
      maintenance immunosuppressive therapy, and the treatment of acute rejection
      episodes. In addition, the agents currently in clinical trials and future
      directions in immunosuppressive therapy are discussed.

PMID- 9531937
TI  - Mechanisms and management of acute renal allograft rejection.
AB  - We used RT-PCR for the molecular characterization of human renal graft rejection.
      The studies showed that intragraft display of mRNA encoding cytotoxic attack
      molecule granzyme B, and immunoregulatory cytokines IL-10 or IL-2 are correlates
      of acute rejection, and intrarenal expression of TGF-1 mRNA, of chronic
      rejection. The current immunosuppressive protocol involves the use of multiple
      drugs, each directed at a discrete site in the T-cell activation cascade and each
      with distinct side effects. The immunosuppressants can be classified as
      inhibitors of: transcription (CsA, tacrolimus); nucleotide synthesis
      (azathioprine, mycophenolate mofetil, and mizoribine); growth factor signal
      transduction (sirolimus); and differentiation (DSG). Polyclonal antibodies and
      monoclonal antibodies directed at cell surface proteins are quite effective as
      induction therapy or anti-rejection drugs.

PMID- 9531938
TI  - Infectious complications following renal transplantation.
AB  - Despite significant advancements in renal transplantation, infectious disease
      complications remain an important cause of morbidity and mortality in the
      transplant recipient. The prevention and treatment of these infections remain a
      major challenge.

PMID- 9531939
TI  - Posttransplant medical complications.
AB  - A variety of medical, surgical, social, and psychiatric problems affect the renal
      allograft rejection, thromboembolic disease, infectious events and
      gastrointestinal disorders. Hypertension and hyperlipidemia appear around 3
      months and may remain throughout the posttransplant period. The late complication
      are atherosclerotic cardiovascular disease, malignancy hepatic failure, chronic
      rejection, denovo and recurrent renal disease, posttransplant diabetes,
      musculoskeletal problems, cataracts and skin lesions. Routine follow up of all
      transplanted patients at specialized centers is critical for early detection and
      management of these complications. Such practice would reduce the patient
      morbidity and mortality and lead to an improved long-term outcome.

PMID- 9531940
TI  - Clinical outcome of renal transplantation. Factors influencing patient and graft
      survival.
AB  - The 1-year graft survival rate for primary cadaver kidney transplants performed
      in the US during the past 9 years was 82%, and it was 94% when living donor
      kidneys were transplanted. After the first year, however, half of the surviving
      cadaveric grafts will fail within 8 years. This late rate has not changed
      substantially in the past 20 years. This article describes some of the factors
      that affect long-term graft and patient survival rates.

PMID- 9531942
TI  - The power of primers.

PMID- 9531941
TI  - An economic analysis of kidney transplantation.
AB  - Kidney transplantation is the most cost-effective treatment modality for end
      stage renal disease (ESRD). Nonetheless, in keeping with the managed care
      mandate, expense has become an increasingly significant issue. Over $11 billion
      is now spent each year on ESRD treatment. Medicare per capita annual payments
      exceed $36,000 per beneficiary. Transplant procedure charges and outcomes vary
      dramatically across the United States. The average charge for a kidney transplant
      is approximately $82,000. Graft and patient survival rates are highly variable,
      even among the most active programs in the US. Individual transplant programs
      must implement approaches to contain their costs and assure quality. At the Mayo
      Clinic, our mean charge for a kidney transplant ($53,510) in 1996 was 27.2% below
      expected, given national medical inflation over the past decade. Unfortunately,
      the net operating income associated with our kidney transplant program has been
      severely eroded in an increasingly brutal economic environment.

PMID- 9531943
TI  - The specific hospital significantly affects red cell and component transfusion
      practice in coronary artery bypass graft surgery: a study of five hospitals.
AB  - BACKGROUND: Interhospital differences in blood transfusion practice during
      coronary artery bypass graft (CABG) surgery have been noted, but the underlying
      issues have not been identified. STUDY DESIGN AND METHODS: Records of 3217
      consecutive CABG cases in five university teaching hospitals in 1992 and 1993
      were stratified by hospital, type of revascularization conduit, patients' sex,
      and other factors. Statistical methods were used to compare patient
      characteristics, transfusion outcomes, and hospital outcomes. RESULTS: Forward
      two-step logistic regression using patient likelihood of red cell transfusion
      factors in the first step and the specific hospital in the second step revealed a
      significant effect of hospital on the delta odds ratios for red cell transfusion.
      This finding was confirmed by analyses of a highly stratified subset of cases,
      males in diagnosis-related group 107 (primary cases of coronary bypass without
      coronary catheterization) who underwent revascularization with venous and
      internal mammary artery grafts, revealing variations among hospitals from 109 to
      457 units of red cells transfused per hundred cases. Corresponding variations in
      transfusions of all blood components were from 324 to 1019 units by hospital.
      Variation in red cell transfusion practice among surgeons in the same hospital
      was not responsible for these interhospital differences. CONCLUSION: The effect
      of the specific hospital on transfusion practice is attributed to institutional
      differences that, through reasons of training or hierarchy, become ingrained in
      hospitals.

PMID- 9531944
TI  - Effects of hyperoxic ventilation on hemodilution-induced changes in anesthetized
      dogs.
AB  - BACKGROUND: In subjects who have undergone acute preoperative normovolemic
      hemodilution (ANH), intraoperative hemorrhage is generally treated by immediate
      return of autologous blood collected during ANH. Simply increasing blood oxygen
      content by hyperoxic ventilation (HV, inspiratory fraction [FIO2] 1.0) might
      compensate for the acute anemia, allow further ANH, and delay onset of autologous
      blood return. STUDY DESIGN AND METHODS: This study 1) evaluated the effects of HV
      (FIO2 1.0) upon ANH to a hemoglobin (Hb) concentration of 7 g per dL in
      anesthetized dogs ventilated with room air and 2) compared the effects of
      subsequent profound ANH (Hb, 3 g/dL) with and without an intravenous
      perfluorocarbon emulsion (perflubron 60% wt/vol) versus those of autologous red
      cell transfusion. The results of the entire study are presented in two parts.
      Organ tissue oxygenation was assessed in skeletal muscle and liver, and systemic
      oxygenation status was evaluated. Myocardial contractility was deduced from left
      ventricular pressure-volume relationship. Seven of 22 dogs underwent further
      hemodilution while breathing 100-percent O2, for a determination of the Hb
      concentration at which HV-induced effects were abolished. RESULTS: HV completely
      reversed the ANH-induced increase in cardiac index (4.6 +/- 0.7 vs. 3.8 +/- 0.9
      L/min/m2 before and during HV; p < 0.05) and partially reversed the decrease in
      systemic vascular resistance (1784 +/- 329 vs. 2087 +/- 524 dyn x cm-5 x sec x m
      2; p < 0.05). Despite unchanged global O2 delivery, organ tissue oxygenation
      improved during HV (mixed venous partial pressure of O2: 40 +/- 3 vs. 59 +/- 7
      torr; coronary venous pressure of O2: 30 +/- 4 vs. 43 +/- 6 torr; p < 0.05; liver
      surface: 31 +/- 11 vs. 39 +/- 13 torr; skeletal muscle surface: 30 +/- 14 vs. 41
      +/- 22 torr; p < 0.05). This improvement was due to an increased contribution of
      physically dissolved O2 in plasma to O2 delivery (3.2 +/- 0.2% before HV vs. 14.6
      +/- 1% during HV; p < 0.05) and O2 consumption (whole body: 6 +/- 1% vs. 47 +/-
      8%, p < 0.05; myocardium: 4.3 +/- 0.9% vs. 31 +/- 6%, p < 0.05). The beneficial
      effects of HV were lost after an additional volume-compensated exchange of 19
      percent of blood volume (Hb, 5.6 g/dL). CONCLUSION: In anesthetized dogs
      ventilated with room air and hemodiluted to a Hb of 7 g per dL, simple oxygen
      therapy by HV (FIO2 1.0) rapidly improves tissue oxygenation and permits extended
      hemodilution to Hb of 5.8 g per dL until the HV-induced effects are lost.

PMID- 9531945
TI  - Hemodilution and intravenous perflubron emulsion as an alternative to blood
      transfusion: effects on tissue oxygenation during profound hemodilution in
      anesthetized dogs.
AB  - BACKGROUND: Intravenously administered perfluorocarbon (PFC) emulsions increase
      oxygen solubility in plasma. PFC might therefore temporarily replace red cells
      (RBCs) lost during intraoperative hemorrhage. In patients who have undergone
      hemodilution, the return of autologous blood may be delayed by the administration
      of PFC, and autologous RBCs may be saved for transfusion after surgical bleeding
      is stopped and PFC is cleared by the reticuloendothelial system. STUDY DESIGN AND
      METHODS: In 22 anesthetized, hemodiluted dogs (hemoglobin [Hb] 7 g/dL) breathing
      100-percent O2, an intraoperative volume-compensated blood loss was simulated.
      The efficacy of three therapeutic regimens in maintaining tissue oxygenation was
      compared: 1) RBC group (n = 7): maintenance of a Hb > 7 g per dL by transfusion
      of autologous RBCs; 2) PFC group (n = 7): bolus application of a second
      generation PFC emulsion (60% wt/vol perflubron) and further acute normovolemic
      hemodilution (ANH) to a Hb of 3 g per dL; and 3) control group (n = 7): further
      ANH alone to a Hb of 3 g per dL. Systemic and myocardial oxygenation status and
      tissue oxygenation were assessed. RESULTS: Autologous RBCs transfused to maintain
      a Hb of 7 g per dL preserved hemodynamics and tissue oxygenation during blood
      loss. In the PFC and control groups, heart rate and cardiac index increased
      significantly in response to further ANH. Tissue oxygenation was not different in
      the PFC and the RBC groups. Direct comparison of the PFC and control groups
      revealed better tissue oxygenation in the PFC group, as reflected by
      significantly higher mixed venous, coronary venous, and local tissue pO2 on liver
      and skeletal muscle. CONCLUSION: Bolus intravenous administration of 60-percent
      (wt/vol) perflubron emulsion and further hemodilution from a Hb of 7 g per dL to
      one of 3 g per dL were as effective as autologous RBC transfusion in maintaining
      tissue oxygenation during volume-compensated blood loss designed to mimic
      surgical bleeding.

PMID- 9531947
TI  - Cryopreservation of single-donor platelets with a reduced dimethyl sulfoxide
      concentration by the addition of second-messenger effectors: enhanced retention
      of in vitro functional activity.
AB  - BACKGROUND: The potential for bacterial contamination limits the storage of
      platelets at 22 degrees C to 5 days. This creates an inventory problem, which
      could be overcome by the use of cryopreservation to allow long-term storage of
      platelets. It has been demonstrated that the addition to platelets of a mixture
      of second-messenger effectors (platelet storage solution), allows these cells to
      retain significant in vitro functional activity following cold storage. Analysis
      is needed of the ability of this second messenger effector mixture both to
      protect platelets during cryopreservation and to reduce the need for a
      cryoprotectant. STUDY DESIGN AND METHODS: Fresh single-donor platelet units (n =
      8) were divided into three samples and treated with 6-percent dimethyl sulfoxide
      (DMSO), 2-percent DMSO or the platelet storage solution and 2-percent DMSO. The
      samples were placed directly into a -80 degrees C freezer and stored for 1 week,
      after which they were thawed and analyzed for in vitro functional activity.
      RESULTS: Platelets cryopreserved with the platelet storage solution and 2-percent
      DMSO displayed statistically higher retention of functional activity and
      viability--including cell number, percent of discoid cells, extent of shape
      change, and hypotonic shock response--than did platelets stored by the method
      using 6-percent DMSO. In addition, the treated platelets displayed statistically
      lower expression of p-selectin. The treated platelets showed no loss of cell
      number, > 88-percent retention of discoid morphology, and > 75-percent retention
      of ristocetin-induced aggregation as compared to values for these measures in
      fresh platelets. CONCLUSION: The use of this platelet storage solution in the
      cryopreservation of platelets yields a significant improvement in their postthaw
      in vitro recovery and allows for a reduction of the DMSO concentration from 6 to
      2 percent, with superior maintenance of in vitro viability and function.

PMID- 9531948
TI  - A clinically applicable method for determining the three major alleles at the
      Duffy (FY) blood group locus using polymerase chain reaction with allele-specific
      primers.
AB  - BACKGROUND: The clinically significant antigens of the Duffy (Fy [FY]) blood
      group system are expressed on the red cell form of the FY glycoprotein, a
      promiscuous chemokine receptor and also a receptor for malarial parasites. After
      the cloning of cDNA coding for FY glycoprotein, the molecular basis of the three
      major alleles (Fya/Fyb/Fy) has been established. Because of the mistyping of the
      silent Fy allele as Fyb, the error rate of current genotyping methods is high in
      black populations. STUDY DESIGN AND METHODS: Two hundred blood donors (European
      whites and African Blacks) and some amniotic DNA samples were investigated by a
      new allele-specific primer polymerase chain reaction technique. Sense primers
      corresponding to normal and GATA-1-mutated FY gene promoter region sequences were
      combined with antisense primers discriminating the Fya/Fyb polymorphism. RESULTS:
      Complete correlation between FY phenotypes and genotypes was obtained in all
      samples studied, although, in two whites and one black, serology showed weak Fyb
      expression while polymerase chain reaction indicated a Fyb allele. Gene
      frequencies were calculated. CONCLUSION: This simple and rapid polymerase chain
      reaction method was shown to detect the three common alleles at the FY locus in
      two representative ethnic populations. Its future use as an independent technique
      in red cell FY investigations and for fetal genotyping in hemolytic disease of
      the newborn is predicted.

PMID- 9531946
TI  - Transforming growth factor beta is increased in plasma of patients with
      hematologic malignancies after transfusion of platelet concentrates.
AB  - BACKGROUND: Transforming growth factor beta 1 (TGF-beta 1) acts as a potent
      inhibitor of bone marrow proliferation. High concentrations were found in human
      platelets, which release this cytokine during storage. STUDY DESIGN AND METHODS:
      TGF-beta 1 levels during a storage period of 5 days were compared in the plasma
      of platelet concentrates prepared by apheresis or by the buffy coat method. In
      addition, TGF-beta 1 plasma levels were monitored in patients with hematologic
      malignancies before and after transfusion. RESULTS: TGF-beta 1 levels in the
      supernatant of platelet concentrates were found to be 55 times higher than those
      in the plasma of healthy volunteer donors. During storage, an additional increase
      was observed. Accordingly, the transfusion of platelet concentrates resulted in a
      significant increase of plasma TGF-beta 1 levels in patients with hematologic
      malignancies (before transfusion: 2.2 +/- 0.5 ng/mL; after transfusion: 2.9 +/-
      0.6 ng/mL), and these higher levels persisted for at least 4 hours. CONCLUSION:
      Because TGF-beta 1 reduces the clonogenic capacity of hematopoetic progenitor
      cells, a myelosuppressive effect of platelet transfusions is suggested.

PMID- 9531949
TI  - Rapid typing of the human Fc gamma receptor IIA polymorphism by polymerase chain
      reaction amplification with allele-specific primers.
AB  - BACKGROUND: The human Fc gamma receptor IIa (Fc gamma RIIa) is expressed in two
      polymorphic forms, Fc gamma RIIa-H131 and Fc gamma RIIa-R131, that differ by the
      replacement of histidine by arginine at position 131. This replacement is caused
      by a single-nucleotide exchange of A-->G. The resulting receptor forms differ in
      their binding to human IgG2 and mouse IgG1, which may lead to a different
      immunologic defense to bacterial polysaccharides and encapsulated bacteria. STUDY
      DESIGN AND METHODS: A rapid and easy polymerase chain reaction(PCR) method of
      genotyping the Fc gamma RIIa was developed. Allele-specific primers discriminate
      between the Fc gamma RIIa-H131 and the Fc gamma RIIa-R131 forms of the receptor.
      The results were compared with those obtained by another DNA-based genotyping
      method, in which PCR-amplified DNA was hybridized with allele-specific
      oligonucleotides, and with a functional phagocytosis assay using mouse IgG1
      coated red cells as target antigens. RESULTS: The genotypes deduced from the PCR
      with allele-specific primers were in complete accordance with those obtained by
      the data from the hybridization of PCR-amplified DNA with allele-specific
      oligonucleotides. Furthermore, the Fc gamma RIIa genotypes of 28 individuals in
      all cases corresponded to the functional phenotypes. CONCLUSION: The use of PCR
      with allele-specific primers provides a rapid and easily performed method for the
      determination the Fc gamma RIIa polymorphism.

PMID- 9531950
TI  - Use of the gel agglutination technique for determination of fetomaternal
      hemorrhage.
AB  - BACKGROUND: Adequate administration of Rh immune globulin requires an accurate
      determination of the number of D-positive cells in the circulation of D-negative
      women. Although several tests have been described for the detection of
      fetomaternal hemorrhage, there is still a need for a rapid, simple, and
      clinically relevant screening test. STUDY DESIGN AND METHODS: Serial dilutions of
      a monoclonal anti-D were incubated with stock solutions (0.2 mL) of adult D
      negative red cells in the absence or presence of various amounts of fetal D
      positive cells (0.1, 0.2, 0.3, 0.4, and 0.5%). After incubation, the supernatants
      were tested against D-positive red cells by using the new, gel agglutination
      technique (GAT). After the GAT was adapted to detect D-positive cells at
      concentrations of > or = 0.2 percent, unselected postpartum samples from D
      negative women (n = 420) who delivered D-positive infants were analyzed by both
      the new test and the Kleihauer-Betke test (KBT). RESULTS: Three of a total of 420
      postpartum samples were positive (> or = 0.4% fetal cells), and 406 were negative
      in both tests. One had 0.5-percent fetal cells in the KBT and gave negative
      results in the GAT. The latter test was, however, performed after administration
      of Rh immune globulin. The KBT gave false-positive results in two cases, because
      of hereditary persistence of hemoglobin F, and the GAT gave a false-positive
      reaction in one case because of a maternal weak D variant. In the remaining seven
      cases, the KBT results were only weakly positive (0.2%) and could not be
      attributed solely to D positive red cells. CONCLUSION: The GAT is suited for
      routine screening. It provides rapid and specific detection of D-positive red
      cells at clinically relevant concentrations. The test may (rarely) yield false
      negative results due to insufficient administration of Rh immune globulin before
      testing.

PMID- 9531951
TI  - The effect of short-term, temporary deferral on future blood donation.
AB  - BACKGROUND: Most blood donor deferrals are temporary and short-term. The effect
      of short-term, temporary deferral (STTD) on blood donor return rates and
      subsequent blood donations is an important issue. STUDY DESIGN AND METHODS:
      Donors given STTDs during the first 3 months of 1993 were computer-matched with
      nondeferred donors on the basis of age, sex, and donation date. Computer records
      were evaluated during the next 4.25 years (4/93-6/97) to determine donor return
      rates and subsequent blood donations. RESULTS: The most common reasons STTD were
      low hemoglobin (46%), colds and/or sore throats (19%), and elevated temperature
      (10%). Nondeferred donors were 29 percent more likely than donors with STTD to
      return over the next 4.25 years (80% vs. 62%), and nondeferred donors donated 81
      percent more whole blood units (13,798 vs. 7,615) over the same period.
      CONCLUSION: The study showed that STTD have a very negative impact on blood donor
      return rates and subsequent blood donations. Actions to alleviate these negative
      effects are indicated.

PMID- 9531952
TI  - A new tool for communicating transfusion risk information.

PMID- 9531953
TI  - Identification and characterization of an HIV-2 antibody-positive blood donor in
      the United States.
AB  - BACKGROUND: As of June 1, 1992, the Food and Drug Administration recommended that
      all donated blood be screened for antibodies specific to HIV-2. Despite broad
      serologic surveillance, only two cases of HIV-2 infection had been detected among
      potential blood and plasma donors since the implementation of the test. CASE
      REPORT: The identification of a third HIV-2 antibody-positive blood donor is
      reported. The first-time donor was identified by routine screening procedures as
      anti-HIV-1/HIV-2-reactive, and that status was confirmed by licensed HIV-1
      Western blot. Concurrent whole-virus lysate enzyme immunoassay and Western blot
      for HIV-2 were strongly positive, but the possibility of HIV-1 cross-reactivity
      could not be eliminated. The donor was notified, counseled, and deferred from
      future donation. He subsequently enrolled in a Centers for Disease Control and
      Prevention-sponsored epidemiologic study of HIV-positive former donors. When it
      was revealed during the standardized interview that he was a native of an HIV-2
      endemic region, follow-up samples were submitted to the Centers for Disease
      Control and Prevention. Investigational HIV-1 and HIV-2 peptide enzyme
      immunoassays indicated that this infection was due to HIV-2 only. CONCLUSION:
      Enzyme immunoassays for antibodies to synthetic peptides of HIV-1 and HIV-2 may
      be useful in differentiating the two viruses in individuals with ambiguous
      Western blot results and risk factors for HIV-2 infection.

PMID- 9531954
TI  - Lack of evidence of hepatitis C infection in 290 blood component recipients,
      demonstrated by several single-antigen research immunoassays.
AB  - BACKGROUND: A group of 290 transfusion recipients enrolled in a prospective study
      of posttransfusion hepatitis was studied to determine the possibility of
      previously unrecognized hepatitis C virus (HCV) transmission. STUDY DESIGN AND
      METHODS: Before and after transfusion, blood specimens that were negative in
      first-generation enzyme immunoassay (EIA) were tested by current commercial EIAs,
      several single-antigen research EIAs, and supplemental tests. RESULTS: Current
      second- and third-generation EIAs identified five subjects (1.7% of total) who
      had chronic hepatitis C before transfusion. Twenty additional sera had some
      reactivity with research EIAs. However, those results were the same before and
      after transfusion (n = 7), had reverted to partially reactive or nonreactive (n =
      8), or could not be confirmed by serologic tests or polymerase chain reaction in
      follow-up specimens (n = 5). CONCLUSIONS: Transient or restricted reactivity to
      HCV antigens measured by more sensitive research EIAs does not seem to correspond
      to recent HCV transmission by transfusion. Whether such reactivity could reflect
      remote HCV infection, with the potential for chronic or intermittent viremia,
      remains to be determined.

PMID- 9531955
TI  - Hematopoietic recovery in cancer patients after transplantation of autologous
      peripheral blood CD34+ cells or unmanipulated peripheral blood stem and
      progenitor cells.
AB  - BACKGROUND: A study of CD34+ cell selection and transplantation was carried out
      with particular emphasis on characteristics of short- and long-term hematopoietic
      recovery. STUDY DESIGN AND METHODS: Peripheral blood stem and progenitor cells
      (PBPCs) were collected from 32 patients, and 17 CD34+ cell-selection procedures
      were carried out in 15 of the 32. One patient in whom two procedures failed to
      provide 1 x 10(6) CD34+ cells per kg was excluded from further analysis. After
      conditioning, patients received CD34+ cells (n = 10, CD34 group) or unmanipulated
      (n = 17, PBPC group) PBPCs containing equivalent amounts of CD34+ cells or
      progenitors. RESULTS: The yield of CD34+ cells was 53 percent (18-100) with a
      purity of 63 percent (49-82). The CD34+ fraction contained 66 percent of colony
      forming units--granulocyte-macrophage (CFU-GM) and 58 percent of CFU of mixed
      lineages, but only 33 percent of burst-forming units-erythroid (BFU-E) (p <
      0.05). Early recovery of neutrophils and reticulocytes was identical in the two
      groups, although a slight delay in platelet recovery may be seen with CD34+ cell
      selection. Late hematopoietic reconstitution, up to 1.5 years after transplant,
      was also similar. The two groups were thus combined for analyses of dose effects.
      A dose of 40 x 10(4) CFU-GM per kg ensured recovery of neutrophils to a level of
      1 x 10(9) per L within 11 days, 15 x 10(4) CFU of mixed lineages per kg was
      associated with platelet independence within 11 days, and 100 x 10(4) BFU-E per
      kg predicted red cell independence within 13 days. However, a continuous effect
      of cell dose well beyond these thresholds was apparent, at least for neutrophil
      recovery. CONCLUSION: CD34+ cell selection, despite lower efficiency in
      collecting BFU-E, provides a suitable graft with hematopoietic capacity
      comparable to that of unmanipulated PBPCs. In both groups, all patients will
      eventually show hematopoietic recovery of all three lineages with 1 x 10(6) CD34+
      cells per kg or 5 x 10(4) CFU-GM per kg, but a dose of 5 x 10(6) CD34+ cells or
      40 x 10(4) CFU-GM per kg is critical to ensure rapid recovery.

PMID- 9531956
TI  - A combination of low-dose cyclophosphamide and colony-stimulating factors is more
      cost-effective than granulocyte-colony-stimulating factors alone in mobilizing
      peripheral blood stem and progenitor cells.
AB  - BACKGROUND: The use of peripheral blood progenitor cells (PBPCs) instead of
      autologous bone marrow leads to more rapid engraftment following high-dose
      chemotherapy. Mobilization regimens differ with respect to toxicity, efficiency,
      and cost. STUDY DESIGN AND METHODS: Two cohorts of patients with breast cancer
      received one of two mobilization regimens: granulocyte-colony-stimulating factor
      (G-CSF) at 10 micrograms per kg was given subcutaneously for 5 days, with
      leukapheresis begun on Day 6, or low-dose cyclophosphamide followed by sequential
      granulocyte-macrophage-CSF (GM-CSF) at 5 micrograms per kg for 5 days and by G
      CSF at 10 micrograms per kg, with leukapheresis begun on Day 11. Results of CD34+
      cell collection, engraftment, and costs of mobilization were determined. RESULTS:
      The combination chemotherapy and growth factor regimen was more efficient in
      mobilizing CD34+ cells. Sixty-six percent of patients reached a target 4 x 10(6)
      CD34+ cells per kg in a single leukapheresis session with the combination
      regimen, compared to 14 percent who received G-CSF alone (p < 0.01). The mean
      number of leukapheresis sessions required to reach a target of 4 x 10(6) CD34+
      cells per kg was 1.3 for the combination regimen and 2.7 for the regimen of G-CSF
      alone (p < 0.01). One patient in the chemotherapy and growth factor group
      developed febrile neutropenia. Engraftment was similar in both cohorts of
      patients. The cost of mobilization, including all supplies and cryopreservation,
      was $7381 for the G-CSF regimen and $5508 for the chemotherapy regimen (p <
      0.05). This reduction was attributed to the lower number of leukapheresis and
      cryopreservation sessions, which outweighed the slight increase in expense for
      chemotherapy and growth factor in the combination regimen. CONCLUSION: This
      combination mobilization regimen allowed the predictable and efficient collection
      of CD34+ cells from the peripheral blood in a limited number of leukapheresis
      sessions, which reduced the cost of mobilization by approximately 25 percent.

PMID- 9531957
TI  - Serologic test for syphilis: a discredited surrogate test for HIV infection.

PMID- 9531958
TI  - Donor attitudes about exporting and importing blood.

PMID- 9531959
TI  - Lipofuscin: mechanisms of formation and increase with age.
AB  - Lipofuscin (age pigment) is a brown-yellow, electron-dense, autofluorescent
      material that accumulates progressively over time in lysosomes of postmitotic
      cells, such as neurons and cardiac myocytes. The exact mechanisms behind this
      accumulation are still unclear. This review outlines the present knowledge of age
      pigment formation, and considers possible mechanisms responsible for the increase
      of lipofuscin with age. Numerous studies indicate that the formation of
      lipofuscin is due to the oxidative alteration of macromolecules by oxygen-derived
      free radicals generated in reactions catalyzed by redox-active iron of low
      molecular weight. Two principal explanations for the increase of lipofuscin with
      age have been suggested. The first one is based on the notion that lipofuscin is
      not totally eliminated (either by degradation or exocytosis) even at young age,
      and, thus, accumulates in postmitotic cells as a function of time. Since
      oxidative reactions are obligatory for life, they would act as age-independent
      enhancers of lipofuscin accumulation, as well as of many other manifestations of
      senescence. The second explanation is that the increase of lipofuscin is an
      effect of aging, caused by an age-related enhancement of autophagocytosis, a
      decline in intralysosomal degradation, and/or a decrease in exocytosis.

PMID- 9531960
TI  - Triggering of renal tissue damage in the rabbit by IgG Fc-receptor-positive group
      A streptococci.
AB  - Our previous studies have shown that streptococcal IgG Fc receptors (FcR) act to
      elicit circulating anti-IgG as well as renal glomerular deposition of IgG in
      rabbits immunized with group A streptococci (GAS). In order to study if other FcR
      positive bacteria might have similar effects, rabbits were immunized with either
      group G streptococci (GGS; strain G148) or Staphylococcus aureus (strain Cowan I)
      for two periods of 8 and 6 weeks, respectively. At the end of immunization,
      circulating anti-IgG was found in 6 of 20 (30%) and 4 of 19 (21%) animals
      receiving G148 and Cowan I, respectively, compared to all 28 receiving FcR
      positive GAS strains of types M1, M4, M15 or M22 (p < 0.05 for both comparisons);
      furthermore, anti-IgG appeared earlier and at higher levels in the GAS groups.
      Weak glomerular IgG deposits occurred in 5 out of 10 (50%) and 2 out of 8 (25%)
      animals immunized with G148 and Cowan I, respectively. In contrast, all 11
      rabbits examined, given GAS of types M1 or M15, displayed heavy deposits. None of
      four control animals immunized with either of two FcR-negative strains, GAS type
      T27 or group B streptococci (GBS) type Ia, exhibited any renal IgG deposits or
      circulating anti-IgG. Renal tissue materials from rabbits immunized with any of
      the four FcR-positive GAS strains showed strong inflammatory and degenerative
      glomerular changes, compatible with the picture seen in acute poststreptococcal
      glomerulonephritis (APSGN). Only transient renal changes were found in those
      rabbits immunized with G148 or Cowan I, or the controls injected with the FcR
      negative strains, GAS type T27 or GBS. Thus, only the FcR-positive GAS strains
      showed capacity to induce high levels of anti-IgG, pronounced tissue deposition
      of IgG as well as irreversible glomerular changes. Our experimental data suggest
      that streptococcal IgG FcR activity might play an important role in triggering
      APSGN.

PMID- 9531961
TI  - Estimation of type-specific anti-streptococcal M-protein antibodies with
      biotinylated peptides in human sera.
AB  - The design of a novel enzyme-linked immunosorbent assay for the estimation of
      antibodies directed against the N-terminus of the M-protein of Streptococcus
      pyogenes is described. The ELISA employs biotinylated peptide antigens of the
      types 1, 4, 12 and 19 immobilized by (strept-)avidin on the surface of
      polystyrene microtiter wells. In rabbit hyperimmune sera and in human serum
      samples, antibodies against the corresponding serotype could be detected with
      high sensitivity and specificity.

PMID- 9531963
TI  - Lung hypoplasia--a possible teratogenic effect of valproate. Case report.
AB  - Three cases of lung hypoplasia occurring in two siblings and in an unrelated
      child are reported. All three cases had been exposed to valproate in utero. The
      two female siblings had no other malformations, whereas the third female had a
      number of defects consistent with the fetal valproate syndrome. Thus, none of the
      known major causes of lung hypoplasia was present in any of the three cases. It
      is discussed whether pulmonary hypoplasia may be a separate disease entity, or
      caused by prenatal exposure to valproate.

PMID- 9531962
TI  - No signs of activity markers in peripheral blood despite increased bronchial
      reactivity after repeated low-dose allergen exposure.
AB  - The allergen inhalation test can be used as an experimental model to study
      pathophysiological events in allergic asthma. Repeated low-dose inhalations of
      allergen induce increased bronchial hyperresponsiveness (BHR) and resemble
      natural allergen exposure. The objective of the present study was to investigate
      whether eosinophil recruitment and activation in peripheral blood, differences in
      expression of lymphocyte surface antigens and increased bronchial responsiveness
      to histamine occur during and after repeated low-dose bronchial allergen
      challenge. Fourteen atopic asthmatic patients were challenged in a randomized
      double-blind manner for 7 days with either allergen in very low doses or placebo.
      We measured the concentration of eosinophils, eosinophil cationic protein (ECP)
      and the expression of the EG2-epitope on intracellular ECP in eosinophils and the
      expression of lymphocyte surface antigen markers in peripheral blood. The
      challenge period started and ended with a histamine provocation. The repeated low
      dose allergen exposure resulted in a significant increase in BHR. No changes were
      seen in the placebo group. Concerning the inflammatory parameters in peripheral
      blood, no significant changes were seen during or after the week of low-dose
      allergen inhalations. Our results show that very low, repeated doses of allergen
      induce increased airway reactivity despite lack of evident clinical symptoms or
      signs of activation of inflammatory cells in peripheral blood.

PMID- 9531964
TI  - Interaction of herpes simplex virus with mononuclear phagocytes is dependent on
      the differentiation stage of the cells.
AB  - The interaction of herpes simplex virus (HSV) with mononuclear phagocytes (MP),
      i.e. monocytes and macrophages, is of importance for the pathogenesis of HSV
      infections. MP are known to play a significant role in the cellular defence
      against infections with HSV, but it has also been shown that HSV-1 affects MP.
      The infection of these cells at different stages of differentiation has different
      outcomes, and may result in the alteration of important cellular functions. HSV-1
      inhibits the morphological differentiation of human monocytes, and this
      inhibition occurs in spite of the fact that human monocytes are non-permissive to
      HSV-1. We have studied the effect of HSV infection of monocytes and macrophages
      on production of essential cytokines and related this effect to the reproduction
      of the virus. Blood-derived MP were cultured in vitro and inoculated with HSV at
      different stages of differentiation. Replication of the virus was measured by
      infectivity titration, detection of HSV antigens by immunofluorescence and
      detection of HSV-specific mRNA. In monocytes, no viral replication and no
      production of late protein was seen. HSV IE gene was transcribed in monocytes
      from some donors, but not from others. In macrophages, virus replicated, but less
      efficiently than in fully permissive fibroblast cells. The production of IL-1
      beta, IL-6 and TNF-alpha in both non-permissive monocytes and permissive
      macrophages was assayed both at the transcriptional level, as mRNA, and as
      protein released from the cells. Production of cytokines by MP was affected by
      HSV-1. The level of cytokine mRNA and cytokine protein did not correspond for all
      cytokines, which may suggest that translational regulation and/or cytokine
      inhibitors are important in the regulation of the cytokine response. The cytokine
      modulation, both at the transcriptional level and measured as biological
      activity, was different in monocytes and macrophages, and varied between
      different donors. Our results indicate a relation between permissiveness and
      cytokine response in mononuclear phagocytes infected with HSV-1. Such a relation
      may be of importance to both intrinsic and extrinsic defence mechanisms of MP
      against HSV-1. Our study also demonstrates that even the functions of non
      permissive cells such as blood-derived monocytes may be affected by viral
      infections.

PMID- 9531965
TI  - Microfilaremia from a Dirofilaria-like parasite in Greece. Case report.
AB  - In Europe, zoonotic filarial infections in humans are caused by two species,
      Dirofilaria immitis and Dirofilaria repens. These parasites are associated mainly
      with embolic infarcts of the pulmonary artery and subcutaneous nodules,
      respectively. An unusual dirofilarial infection in a Greek patient who showed
      marked eosinophilia and microfilaremia is presented. Although the identification
      of Dirofilaria species is not conclusive, this report is the first on a case of
      microfilaremia from a Dirofilaria infection in an immunocompetent patient.

PMID- 9531966
TI  - Induction of cytokines and expression of surface receptors in Mono Mac 6 cells
      after infection with different Legionella species.
AB  - The ability of Legionella species to multiply within human mononuclear phagocytes
      is usually regarded as being associated with their pathogenicity. Activation of
      host cells results in inhibition of intracellular Legionella multiplication. The
      most effective substance to induce macrophage activation, both in vivo and in
      vitro, is interferon-gamma. In addition, some evidence exists that macrophage
      derived cytokines may contribute to the host defense against L. pneumophila, but
      the production of pro- and antiinflammatory cytokines by monocytes after
      infection with different Legionella species has not been reported with regard to
      their ability to multiply within the host cells. We therefore examined the
      production of TNF-alpha, IL-1, IL-6, IL-8, IL-10 and TGF-beta by Mono Mac 6 cells
      after infection with Legionella species of different human prevalence that differ
      in their ability to replicate within this macrophage-like cell line. After
      infection, Mono Mac 6 cells showed a cytokine response with time kinetics
      characteristic for the cytokine. Maximum cytokine levels produced differed with
      Legionella species, but were not related to intracellular multiplication rates.
      Moreover, LPS-tolerant Mono Mac 6 cells, which failed to produce cytokines,
      showed intracellular increase or decrease of bacterial numbers identical to that
      of untreated Mono Mac 6 cells. By FACS analysis, an up-regulation of CD14 (LPS
      receptor) and CD54 (ICAM-1) could be demonstrated. We conclude that, in the Mono
      Mac 6 cell line, induction of macrophage-derived cytokines after infection with
      members of the genus Legionella mimics an inflammatory reaction without
      association with intracellular multiplication rate.

PMID- 9531967
TI  - Viremia in chronic hepatitis C patients evaluated by the Amplicor RT-PCR, a
      nested RT-PCR, and transaminase levels.
AB  - A commercially available kit, Amplicor, was compared with a locally developed
      nested reverse-transcriptase (RT) PCR for qualitative detection of HCV-RNA. Sixty
      one serum samples from sixty-one patients with liver disease, and 60 samples from
      60 hemophiliacs without symptoms, but known to have been heavily exposed to
      hepatitis C virus, were investigated. There was a high degree of concordance
      between the two diagnostic tests (97%), the Amplicor kit being slightly more
      sensitive than the in-house PCR, when evaluated using serial dilutions of samples
      showing discrepant results. The relationship between viremia and abnormal ALT
      levels was studied in the two groups of patients. Among those with chronic liver
      disease, 8.3% of patients with viremia had normal ALT levels, whereas
      transaminases were normal in 20% of hemophiliacs with viremia. This points to ALT
      as being a poor marker of ongoing viral replication.

PMID- 9531968
TI  - Morphological adaptations of human liver peroxisomes in cholestasis.
AB  - Part of the bile acid synthesis takes place in peroxisomes. An altered
      enterohepatic circulation of bile acids might influence peroxisomal beta
      oxidation enzymes and peroxisomal morphology. We performed a morphological and
      morphometric investigation of peroxisomes in liver biopsy samples of eight
      patients with cholestasis of different origin: graft versus host reaction (n =
      1), obstruction of the bile flow (n = 3), and drug-induced cholestatic hepatitis
      (n = 4). Peroxisomes were identified using catalase cytochemistry. They were
      regularly shaped and showed individual differences in electron density. A
      perinuclear distribution was observed in a variable number of hepatocytes in each
      sample. Morphometric analysis of peroxisomes revealed an increase in numerical
      density and surface density in all, and a decreased mean diameter in four liver
      samples. Based on previously obtained data in experimental animals, we
      hypothesize that the observed alterations in peroxisomal morphology indicate an
      enhanced metabolic activity of the enzymes in the peroxisomal matrix. Among them
      are enzymes involved in bile acid synthesis.

PMID- 9531969
TI  - Sorting out adaptors.

PMID- 9531970
TI  - L is for lytic granules: lysosomes that kill.
AB  - CTL are important cells in the immune system which are able to recognise and
      directly destroy virally infected, tumorigenic or foreign cells. The proteins
      which mediate this destruction are packaged into specialised secretory granules,
      termed lytic granules, which are secreted in response to target cell recognition.
      Curiously these specialised secretory granules also contain all the lysosomal
      hydrolases, and in CTL the lytic granules serve two separate functions: as a
      lysosome within the cell, and as a secretory granule when a target cell is
      recognised. These "secretory lysosomes", which serve important roles in both
      protein degradation within the cells as well as regulated secretion of proteins
      from the cells, are also found in other cell types, all of which are derived from
      the hemopoietic lineage. This observation raises the possibility that cells of
      the hemopoietic lineage possess specialised sorting and secretory mechanisms
      which allow the lysosomes to be used as secretory organelles. Studies on Chediak
      Higashi syndrome support this idea, since in this naturally occurring genetic
      mutation, cells with secretory lysosomes are unable to secrete their granules
      while other conventional secretory cells are able to do so. Further studies on
      the mechanisms which regulate secretion of lytic proteins from CTL should
      identify the proteins involved in this unusual secretory pathway. Some aspects of
      the differences between conventional and "secretory" lysosomes remain unresolved.
      How the biogenesis of the secretory lysosome differs from that of a conventional
      secretory granule is unclear. While conventional secretory cells sort proteins
      destined for the granule by a selective condensation in the TGN, the secretory
      lysosomes seem to use a combination of lysosomal and other sorting signals. Our
      preliminary studies suggest that haemopoietic cells possess specialised sorting
      mechanisms which allow the correct sorting of the secreted products to the
      lysosome, and that these signals are different from those found in conventional
      secretory (e.g. neurosecretory) cells. This finding and the observation that
      fibroblast lysosomes can undergo calcium-mediated exocytosis suggests that the
      unusual secretory system found in haemopoietic cells may be a result of
      specialised sorting mechanisms in these cells. In this case the Chediak lesion
      may turn out to be a sorting defect.

PMID- 9531971
TI  - PMA alters folate receptor distribution in the plasma membrane and increases the
      rate of 5-methyltetrahydrofolate delivery in mature MA104 cells.
AB  - MA104 cells (a monkey kidney cell line) can internalize 5-methyltetrahydrofolate
      via a receptor mediated process termed potocytosis. Uptake is initiated by
      binding to an external folate receptor which cycles to an internal, but membrane
      bound compartment. These two pools can be measured by determining the amount of
      [3H]ligand removed by an acid-saline wash, i.e. acid labile and acid resistant
      pools. When assayed in confluent nonmitotic cells, 2/3 of the folate receptor
      pool is located in an internal (acid resistant) compartment, but phorbol 12
      myristate 13-acetate (PMA) causes a shift such that 65-75% of the receptor pool
      resides on the surface of the plasma membrane. This new steady state is likely
      the result of an increased rate of receptor movement. In addition, PMA increases
      the rate of 5-methyl[3H]tetrahydrofolate delivery to the cytoplasm 1.8 fold.
      Using known inhibitors of potocytosis, we were able to show that the increased
      rate of delivery is receptor mediated. Comparison of the time courses of the PMA
      effects on folate receptor redistribution assessed by membrane binding of
      [3H]folic acid and 5-methyl[3H]tetrahydrofolate delivery to the cytoplasm
      suggests that PMA may be activating more than one protein kinase C independent
      signal transduction pathway. PMA is the first reported positive modulator of
      receptor mediated folate uptake.

PMID- 9531972
TI  - The acute-phase protein alpha 1-antitrypsin inhibits transferrin-receptor binding
      and proliferation of human skin fibroblasts.
AB  - Transferrin (Tf) is required for proliferation of most cells, because cellular
      iron uptake is mainly mediated by binding of Tf to its specific cell surface
      receptors (TfR). The acute-phase protein alpha 1-antitrypsin (alpha 1-AT)
      completely inhibits binding of diferric Tf to TfRs on human skin fibroblasts in a
      dose-dependent fashion. The inhibition is competitive as proved in equilibrium
      saturation binding and kinetic studies. In saturation binding experiments alpha 1
      AT apparently increased the dissociation constant (KD), but did not change the
      maximal density of binding sites (Bmax). As shown in kinetic studies, this
      reduction of the affinity of Tf to its receptor caused by alpha 1-AT was due to a
      decrease of the association rate constant (k + 1), whereas the dissociation rate
      constant (k - 1) remained unchanged. Furthermore, alpha 1-AT almost completely
      prevented internalization of the Tf-TfR complex. These interactions demonstrated
      biological implication, as alpha 1-AT reduced the proliferation of human
      fibroblasts up to maximal 30% of control. The inhibitory potency of alpha 1-AT
      was already seen in physiologic concentrations; the maximal effect, however, was
      achieved at concentrations above the normal range, which are attained in the
      course of inflammation and infection. Therefore, we suppose that alpha 1-AT as an
      endogenous factor modulates the complex mechanism of fibrogenesis not only by its
      known antiproteolytic function but also by inhibiting the proliferation of
      fibroblasts.

PMID- 9531973
TI  - Identification and androgen regulation of egasyn in the mouse epididymis.
AB  - The expression and androgen regulation of egasyn, the endoplasmic reticulum
      targeting protein of beta-D-glucuronidase, was examined in the mouse-epididymis.
      The proximal (caput) and distal (corpus & cauda) epididymal tissue extracts were
      prepared by homogenization and sonication in buffered Triton X-100 solution, and
      high speed centrifugation. The supernatant when resolved by 2D-PAGE under non
      denaturing conditions and stained for esterase activity showed that the distal
      (but not proximal) epididymis of the normal mouse contain several specific forms
      of esterases. These forms include a series of four variants (pI 5.2-5.75) with
      high mobility (HM) and esterase activity, and three faintly staining variants
      (beginning at pI 6.0) with low mobility (LM). Several lines of evidence indicate
      that the specific esterases seen in the corpus/cauda epididymidis are egasyn
      esterases. Firstly, these molecular forms were not seen in the distal epididymal
      extracts from the egasyn-deficient mouse. Secondly, the HM forms can be
      immunoprecipitated with anti-egasyn antibody, suggesting the presence of free
      egasyn. Finally, the LM forms disappeared after heat treatment (56 degrees C for
      8 min), a condition known to dissociate egasyn:beta-D-glucuronidase complex. This
      result indicates that a small amount of egasyn is complexed with beta-D
      glucuronidase. Immunoblotting (Western blot) studies (using anti-egasyn antibody)
      following resolution of egasyn released from the egasyn:beta-D-glucuronidase
      complex revealed a single band of an apparent molecular weight 64 kDa in the
      distal (but not proximal) epididymis, indicating that the mouse epididymal egasyn
      is identical or very similar to the liver egasyn. Castration of mice lead to the
      appearance of free and complexed egasyn forms in the proximal epididymis.
      Testosterone supplementation to the castrated mice resulted in the disappearance
      of the induced egasyn forms from the caput epididymidis. Taken together, these
      results indicate that the expression of egasyn in the epididymis is region
      specific and is differentially regulated by androgens.

PMID- 9531974
TI  - Upregulation of vascular endothelial growth factor by angiotensin II in rat heart
      endothelial cells.
AB  - Vascular endothelial growth factor (VEGF) is a potent mitogen for endothelial
      cells and a vascular permeability factor. In this study we found that the
      addition of angiotensin II (AII) to rat heart endothelial cells induced VEGF mRNA
      production. VEGF mRNA levels reached a plateau within 2 h after the addition of
      AII and decreased after 4 h. The induction was superinduced by cycloheximide and
      blocked by actinomycin D. Losartan, an AT1 receptor antagonist, abolished the
      induction of VEGF mRNA by AII, whereas PD 123319, an AT2 receptor antagonist, had
      no effect on VEGF mRNA induction. H7, a protein kinase C inhibitor, blocked the
      induction. RT-PCR experiments showed two mRNA species (VEGF 120 and VEGF 164) in
      these cells and both species were stimulated by AII. Transient transfection
      experiment showed that VEGF promoter activity was increased 2.2-fold upon AII
      stimulation. Electrophoretic mobility shift assay revealed an enhanced binding of
      transcription factors AP-1 and NF-kappa B. Immunoblot analysis showed that the
      amount of secreted VEGF was elevated in the medium 8 h after AII stimulation. Our
      results demonstrate for the first time that the upregulation of VEGF by AII may
      play a significant role in AII-induced hyperpermeability.

PMID- 9531975
TI  - High pressure conditions promote the proliferation of rat cultured mesangial
      cells in vitro.
AB  - Glomerular capillary pressure is involved in the development of chronic renal
      failure and has at least two effects on mesangial cells: transmembrane
      hydrostatic pressure and stretch. To clarify whether pure hydrostatic pressure
      itself affects the proliferation of cultured rat mesangial cells, we compared the
      cell number under atmospheric pressure condition with high pressure condition. At
      24 and 48 h with 0.5% serum, cell number was significantly higher under high
      pressure condition than under atmospheric pressure condition. At 48 h, cell
      number under high pressure condition was increased in a pressure-dependent
      manner. Furthermore, flow cytometric assay indicated that pressure-load could
      promote DNA synthesis rate at S phase and enhance G1/S progression induced by low
      concentration of serum (0.5%). These results suggest that pure hydrostatic
      pressure itself can promote the proliferation of cultured rat mesangial cells by
      advancing cell cycle progression in vitro.

PMID- 9531976
TI  - Presence of laminin fragments in cyst fluid from patients with autosomal dominant
      polycystic kidney disease (ADPKD): role in proliferation of tubular epithelial
      cells.
AB  - Cyst fluid samples obtained from eight patients with autosomal dominant
      polycystic kidney disease (ADPKD) were analysed for the presence of the basement
      membrane component laminin and its breakdown products, using ELISA and
      immunoblotting techniques. Whole laminin was not detected, whereas laminin
      fragments of 270, 155, 87, 56, and 14 kDa were detected at a mean total value of
      approximately 0.5 microgram/ml. The laminin fragments were assessed for their
      effect on cultured normal and ADPKD epithelial cells. Both cell types showed
      accelerated growth under these conditions. These findings suggest that basement
      membrane degradative fragments present in cyst fluid may contribute to cystic
      epithelial cell proliferation and may therefore be important in the pathogenesis
      of ADPKD.

PMID- 9531977
TI  - Downregulated expression of the signaling molecules Nck, c-Crk, Grb2/Ash, PI 3
      kinase p110 alpha and WRN during fibroblast aging in vitro.
AB  - An RT-PCR analysis was performed to examine changes in intracellular signal
      transducing molecules during in-vitro aging of human fibroblasts. Expression of
      Nck, c-Crk, Grb2/Ash, phosphoinositide (PI) 3-kinase p110 alpha and Werner's
      syndrome gene product WRN was noticeably reduced in late passage cells, showing a
      concurrent downregulation of a set of signaling molecules accompanying aging.

PMID- 9531978
TI  - Cloning of the rat brain cDNA encoding for the SLC-1 G protein-coupled receptor
      reveals the presence of an intron in the gene.
AB  - In order to isolate new G protein-coupled receptors expressed in the cerebral
      cortex, a set of degenerate oligonucleotides corresponding to the third and
      seventh transmembrane segment were synthetized. Their use in PCR on rat brain
      cortex mRNA amplified several cDNA fragments. One of them, a 526 bp sequence,
      encoded for what was at that time an unknown G protein-coupled receptor. An
      oligonucleotide derived from the sequence was then used as a probe to isolate the
      receptor cDNA from a rat brain cDNA library. It encodes for a 353aa protein with
      seven transmembrane segments, three consensus N-glycosylation sites at the amino
      terminus and several potential phosphorylation sites in the intracellular loops.
      This protein shares 91% overall identity with a recently cloned human
      somatostatin-like receptor of 402aa named SLC-1. This suggests that we have
      cloned the rat orthologue of the human SLC-1. However, the extracellular N
      terminus of the human receptor is 49 amino acids longer and shows 50% identity
      with the rat one. Because the human sequence was deduced from genomic DNA, we
      suspected the presence of an intron in the gene. This was confirmed by PCR using
      primers spanning the intron. On the basis of the sequence of a 128 kb fragment of
      chromosome 22 encompassing the SLC-1 gene, we were able to deduce a corrected
      amino acids sequence for the human receptor. So both rat and human SLC-1
      receptors are 353aa long, with three consensus N-glycosylation sites. They share
      96% identity at the amino acid level and are encoded by a gene containing one
      intron in the coding sequence.

PMID- 9531980
TI  - WA8242A1, A2 and B, novel secretory phospholipase A2 inhibitors produced by
      Streptomyces violaceusniger. I. Taxonomy, production and purification.

PMID- 9531979
TI  - Growth regulation of primary human keratinocytes by prostaglandin E receptor EP2
      and EP3 subtypes.
AB  - We examined the contribution of specific EP receptors in regulating cell growth.
      By RT-PCR and northern hybridization, adult human keratinocytes express mRNA for
      three PGE2 receptor subtypes associated with cAMP signaling (EP2, EP3, and small
      amounts of EP4). In actively growing, non-confluent primary keratinocyte
      cultures, the EP2 and EP4 selective agonists, 11-deoxy PGE1 and 1-OH PGE1, caused
      complete reversal of indomethacin-induced growth inhibition. The EP3/EP2 agonist
      (misoprostol), and the EP1/EP2 agonist (17-phenyl trinor PGE2), showed less
      activity. Similar results were obtained with agonist-induced cAMP formation. The
      ability of exogenous dibutyryl cAMP to completely reverse indomethacin-induced
      growth inhibition support the conclusion that growth stimulation occurs via an
      EP2 and/or EP4 receptor-adenylyl cyclase coupled response. In contrast,
      activation of EP3 receptors by sulprostone, which is virtually devoid of agonist
      activity at EP2 or EP4 receptors, inhibited bromodeoxyuridine uptake in
      indomethacin-treated cells up to 30%. Although human EP3 receptor variants have
      been shown in other cell types to markedly inhibit cAMP formation via a pertussis
      toxin sensitive mechanisms, EP3 receptor activation and presumably growth
      inhibition was independent of adenylyl cyclase, suggesting activation of other
      signaling pathways.

PMID- 9531982
TI  - Novel lactone compounds from Mortierella verticillata that induce the human low
      density lipoprotein receptor gene: fermentation, isolation, structural
      elucidation and biological activities.
AB  - Among methods of controlling hypercholesterolemia and hyperlipidemia is the
      direct stimulation of hepatic low density lipoprotein (LDL) receptors. Two novel
      lactone compounds, CJ-12,950 and CJ-13,357, containing and unusual oxime moiety,
      were isolated from a zygomycete Mortierella verticillata. These lactones are
      potent inducers of the LDL receptor gene in vitro, that enhanced LDL receptor
      expression in human hepatocytes 2-fold at 100 nM.

PMID- 9531981
TI  - WA8242A1, A2 and B, novel secretory phospholipase A2 inhibitors produced by
      Streptomyces violaceusniger. II. Biological properties.
AB  - WA8242A1, A2 and B, novel inhibitors of secretory phospholipase A2 (PLA2), were
      obtained from Streptomyces violaceusniger No. 8242. WA8242B inhibited secretory
      group I and II PLA2s in a dose-dependent manner. The mode of inhibition of group
      II PLA2 by WA8242B was in competitive fashion. WA8242B inhibited group II PLA2
      induced Prostaglandin I2 (PGI2) production by human umbilical vein endothelial
      cells. Furthermore, WA8242B was effective in mouse zymosan writhing model.

PMID- 9531983
TI  - Polyketomycin, a new antibiotic from Streptomyces sp. MK277-AF1. I. Taxonomy,
      production, isolation, physico-chemical properties and biological activities.
AB  - A new antibiotic designated polyketomycin was isolated from the culture broth of
      Streptomyces sp. MK277-AF1. It was purified by ethyl acetate extraction, Sephadex
      LH-20 column chromatography and centrifugal partition chromatography (CPC). It
      inhibited growth of Gram-positive bacteria including methicillin-resistant
      Staphylococcus aureus (MRSA). Its MICs were less than 0.2 microgram/ml.
      Polyketomycin exhibited cytotoxic activity against nine tumor cell lines at
      concentrations of 0.9-5.2 micrograms/ml.

PMID- 9531984
TI  - Polyketomycin, a new antibiotic from Streptomyces sp. MK277-AF1. II. Structure
      determination.
AB  - A new antibiotic, polyketomycin, was isolated from the culture broth of
      Streptomyces sp. MK277-AF1. The structure was determined by various NMR
      spectroscopies, X-ray crystallographic analysis and degradation experiments.

PMID- 9531985
TI  - Cytotoxic substances produced by a fungal strain from a sponge: physico-chemical
      properties and structures.
AB  - Five novel metabolites, trichodenones A-C (1-3), harzialactone A (4) and B (5),
      have been isolated together with known R-mevalonolactone (6) from the culture
      broth of a strain of Trichoderma harzianum OUPS-N115 originally separated from
      the sponge Halichondria okadai. Their structures have been elucidated by spectral
      evidence. Among them, 1-3 exhibited significant cytotoxicity against cultured
      P388 cells.

PMID- 9531986
TI  - Isolation and characterisation of an antifungal antibiotic (GR135402) with
      protein synthesis inhibition.
AB  - A novel antifungal antibiotic GR135402 has been isolated from a fermentation
      broth of Graphium putredinis which inhibited protein synthesis in Candida
      albicans but not rabbit reticulocytes. The spectrum of activity included C.
      albicans and Cryptococcus neoformans but not some other Candida species or
      Aspergillus species. Therapeutic efficacy in a mouse model of systemic candidosis
      was attained following parenteral dosing.

PMID- 9531987
TI  - Cloning and heterologous expression of genes from the kinamycin biosynthetic
      pathway of Streptomyces murayamaensis.
AB  - The genes for most of the biosynthesis of the kinamycin antibiotics have been
      cloned and heterologously expressed. Genomic DNA of Streptomyces murayamaensis
      was partially digested with MboI and a library of approximately 40 kb fragments
      in E. coli XL1-BlueMR was prepared using the cosmid vector pOJ446. Hybridization
      with the actI probe from the actinorhodin polyketide synthase genes identified
      two clusters of polyketide genes. After transferal of these clusters to S.
      lividans ZX7, expression of one cluster was established by HPLC with photodiode
      array detection. Peaks were identified from the kin cluster for
      dehydrorabelomycin, kinobscurinone, and stealthin C, which are known
      intermediates in kinamycin biosynthesis. Two shunt metabolites, kinafluorenone
      and seongomycin were also identified. The structure of the latter was determined
      from a quantity obtained from large-scale fermentation of one of the clones.

PMID- 9531988
TI  - Overproduction of rifamycin B by Amycolatopsis mediterranei and its relationship
      with the toxic effect of barbital on growth.
AB  - A novel method for selecting overproducing strains of rifamycin B was developed.
      This technique involves the use of lysozyme and the effect of barbital on the
      growth of A. mediterranei. Complete medium added with glycine and barbital was
      inoculated with mutagenized mycelium, incubated for 48 hours and treated with
      lysozyme. The lysozyme resistant mycelium was washed with dilute detergent.
      Complete medium with glycine but without barbital was inoculated with the washed
      mycelium. Protoplasts were obtained and regenerated and the colonies were picked
      and seeded on Bennet agar plates with and without barbital. Two selected mutants
      were sensitive to 0.5% barbital producing 200% more rifamycin than the parental
      strain. In addition, 30 barbital resistant mutants were isolated and their
      production level was lower than the one observed with the parental strain. These
      results suggest that the effect of barbital on secondary metabolism (rifamycin
      production) is related to its effect on primary metabolism.

PMID- 9531989
TI  - Enhancement of drug accumulation by andrastin A produced by Penicillium sp. FO
      3929 in vincristine-resistant KB cells.
AB  - In the course of our screening for compounds that reverse multidrug resistance,
      we found that the cytotoxicity of vincristine was enhanced 1.5-20-fold depending
      on the concentration of andrastin A in vincristine-resistant KB cells (VJ-300).
      Andrastin A alone had no effect on the growth of drug sensitive KB cells and VJ
      300 cells. On the other hand, andrastin A (25 and 50 micrograms/ml) significantly
      enhanced accumulation of [3H]vincristine in VJ-300 cells. Andrastin A (50
      micrograms/ml) completely inhibited the binding of [3H]azidopine to the P
      glycoprotein in VJ-300 cells. The result suggests that andrastin A directly
      interacts with P-glycoprotein and inhibits the efflux of antitumor agents in drug
      resistant cells.

PMID- 9531990
TI  - Mono and double modified teicoplanin aglycon derivatives on the amino acid no. 7;
      structure-activity relationship.
AB  - A series of 7d-aminomethylated derivatives (mono modified) and their amides
      (double modified) at the amino acid No. 7 of teicoplanin aglycon were prepared
      with the aim of obtaining activity against vancomycin-resistant VanA enterococci.
      Among mono modified compounds, the 7d-n-decylaminomethyl derivative was the most
      active against VanA enterococci (4 micrograms/ml). Amides of the latter with 3
      dimethylamino-propylamine or methylamine were found to be up to four times more
      active against glycopeptide-susceptible Gram-positive bacteria, and up to four
      times less active against VanA enterococci than the starting compound.

PMID- 9531991
TI  - 6-Hydroxytetrangulol, a new CPP32 protease inducer produced by Streptomyces sp.

PMID- 9531992
TI  - 1-Hydroxycrisamicin A, a new isochromanquinone antibacterial antibiotic, produced
      by Micromonospora sp. SA246.

PMID- 9531993
TI  - Identification of the anthracycline antibiotic 4-O-(beta-D-glucopyranuronosyl)
      epsilon-rhodomycinone, produced by Streptomyces ruber JCM3131, as an up-regulator
      of MHC class-I molecules in B16/BL6 cells.

PMID- 9531994
TI  - Histone deacetylase inhibitors up-regulate the expression of cell surface MHC
      class-I molecules in B16/BL6 cells.

PMID- 9531995
TI  - Suppression of T cell stimulating function of allogeneic antigen presenting cells
      by prodigiosin 25-C.

PMID- 9531996
TI  - Neocarzinostatin-chromophore: a potent inhibitor of casein kinase II in vitro.

PMID- 9531997
TI  - [Changing trends in radiology].

PMID- 9531998
TI  - Recommendations for the examination of peripheral nerve biopsies.
AB  - Peripheral nerve biopsy is now an established, valuable investigative procedure,
      but as it can give rise to significant residual symptoms it should only be
      undertaken after careful consideration of the indications and with informed
      consent from the patient. Nerve biopsies should only be processed and evaluated
      in a laboratory with the relevant particular expertise. It is generally
      recommended that a sural nerve biopsy be performed in combination with a muscle
      biopsy but not vice versa (muscle biopsies together with a nerve biopsy). Nerve
      biopsy is not the only means of sampling peripheral nerve tissue to study the
      peripheral nervous system. Examination of the innervation of the skin may be
      informative. The same is likely to be true for motor point muscle biopsy. Nerve
      biopsy is mainly used for morphology although molecular genetic techniques using
      fresh or archival nerve biopsies are increasingly available. Chemical analysis is
      undertaken mainly for research purposes.

PMID- 9531999
TI  - Expression of cyclin D1, retinoblastoma gene protein, and p16 MTS1 protein in
      atypical adenomatous hyperplasia and adenocarcinoma of the lung. An
      immunohistochemical analysis.
AB  - To clarify the events leading to the disruption of cell growth control that
      occurs during the development of pulmonary adenocarcinoma (AC), we used
      immunohistochemistry to evaluate the expression of G1 cycle regulators, cyclin
      D1, Rb protein (pRb), and p16 MTS1 protein and the tumour proliferation marker,
      Ki 67, both in AC of the lung and in its precursor lesion, atypical adenomatous
      hyperplasia (AAH). The frequency of lesions with cyclin D1 overexpression was
      relatively high in AAH (47-89%), but was decreased in early AC (28%) and overt AC
      (35%). The loss of pRb expression was rare in both AAH (0-18%) and early AC (0%),
      and was infrequent even in overt AC (13%). The loss of p16 expression was also
      relatively infrequent in both the premalignant and the malignant lesions (11
      25%). Our results suggest that overexpression of cyclin D1 is an early event and
      plays an important part in tumorigenesis in the case of lung AC. However, cyclin
      D1 overexpression is not required for the development and maintenance of a
      malignant phenotype. It is likely that some cyclin D1-independent pathways other
      than Rb and p16 abnormalities have an important role in the malignant
      transformation from AAH to early AC.

PMID- 9532000
TI  - Characterization of the inflammatory infiltrate in autoimmune cholangitis. A
      morphological and immunhistochemical study.
AB  - Autoimmune cholangitis (AIC) is characterised by clinical and/or laboratory
      features of cholestasis, the presence of antinuclear antibodies and the lack of
      antimitochondrial antibodies. Histologically, changes largely identical to those
      found in primary biliary cirrhosis (PBC) are typically found. It is not possible
      to differentiate between AIC and PBC on conventional morphological grounds, and
      we therefore wished to find whether there is a difference between these entities
      in the composition of the inflammatory infiltrate leading to bile duct
      destruction. In liver biopsies from ten patients with confirmed AIC and ten
      patients with PBC the inflammatory infiltrate was characterised with antibodies
      against CD 3, OPD 4 CD 8, GB 7, L 26, CD 56 and CD 57. In AIC, T cells were
      predominant in the portal inflammatory infiltrate in nine cases. Granzyme B
      positive activated cytolytic T lymphocytes were found in the bile duct epithelium
      in five cases. All these five cases showed inflammatory bile duct destruction. No
      significant differences between the immunohistochemical findings in AIC and in
      PBC were found. We suggest that AIC is a subgroup of PBC, antimitochondrial
      antibody-negative type.

PMID- 9532001
TI  - Membranous fat necrosis in appendices epiploicae. A clinicopathological study.
AB  - Membranous fat necrosis (MFN) is a degenerative process involving mature systemic
      adipose tissue. It is characterised by the presence of membranocystic foci
      surrounded by a lipophagic fibro-inflammatory reaction typical of fat necrosis.
      Membranocystic foci are cysts lined by an eosinophilic membrane with
      pseudopapillary infoldings having the histochemical staining profile of ceroid.
      Although MFN is described in an increasing number of adipose tissue sites, it has
      not been described as a distinct entity in appendices epiploicae (AE).
      Macroscopically, MFN in AE mimics nodal tuberculosis or metastatic tumour with
      necrosis and cystic change. Ischaemia, which can be secondary to physiological or
      pathologic processes, is crucial in the pathogenesis of MFN in AE. Heightened
      awareness of MFN as a distinct entity in AE is essential for accurate diagnosis
      and establishment of the pathogenesis of this enigmatic pathological process.

PMID- 9532002
TI  - Ultrastructural pathology of the alveolar type II pneumocytes of human donor
      lungs. Electron microscopy, stereology, and microanalysis.
AB  - Alveolar type II pneumocytes (PII) were studied in 12 human donor lungs perfused
      with modified Euro-Collins solution during single-lung transplantation (SLTx).
      While one lung was transplanted, the contralateral donor lung (cDL) was fixed at
      the time of SLTx for examination by electron microscopy, stereology, and
      microanalysis. Three groups were then formed: group A (n = 7), cDL without
      contusions, uneventful early postoperative course; group B (n = 3), cDL with
      conclusions, uneventful early postoperative course; group C (n = 2), cDL without
      contusions, early postoperative respiratory dysfunction. The major findings were
      that the presence of contusions had no effect on PII ultrastructure and that
      intracellular surfactant-storing lamellar bodies of cDL in group C were
      characterized by a higher volume-to-surface ratio (VsR) and larger area per cell
      profile than group A. Correlation analysis based on pooled data (groups A and C)
      showed that ischaemic time had little effect on PII ultrastructure and bore no
      relationship to postoperative clinical variables. The duration of preoperative
      donor intubation had a pronounced influence on ultrastructure and postoperative
      clinical variables. The stereologically estimated amount of intracellular
      surfactant and mitochondrial VsR were the only ultrastructural parameters that
      were significantly associated with early postoperative oxygenation. Lamellar
      bodies were the only ultrastructural components found to have a significant
      relationship to postoperative intubation time. The ultrastructural integrity of
      type II pneumocytes of human donor lungs is an important determinant of early
      respiratory function following clinical lung transplantation.

PMID- 9532003
TI  - Localization of insulin-like growth factor-II mRNA in human pituitary adenomas.
AB  - Insulin-like growth factors (IGFs) have been reported to promote cell
      proliferation in many tumours, but their contribution to pituitary adenoma
      development and growth has not been characterized. We report the presence of
      insulin-like growth factor II (IGF-II) mRNA in pituitary adenomas using in situ
      hybridization (ISH). The intensity of IGF-II hybridization signal was correlated
      with adenoma type, and the presence of Ki-67. Among the 109 adenomas examined, 55
      (50.4%) were positive for IGF-II mRNA. All acidophil stem cell, functioning
      corticotrophic and plurihormonal adenomas contained the message; a high incidence
      of signal was found among sparsely (7/8) and densely (4/6) granulated growth
      hormone (GH) cell adenomas, mixed GH cell-prolactin (PRL) cell adenomas (6/7),
      thyrotrophic (4/6) and null-cell (6/7) adenomas. Less frequently, IGF-II mRNA was
      localized in mammosomatotrophic, silent subtype 3, gonadotrophic, and oncocytic
      adenomas, whereas all sparsely granulated PRL cell adenomas and silent
      corticotrophic adenomas of subtypes 1 and 2 were negative. The MIB-I labelling
      index was significantly higher in adenomas with a moderate to intense IGF-II
      signal than in adenomas with weak or no signal. The results suggest that IGF-II,
      when highly expressed, may have a role in pituitary adenoma proliferation.

PMID- 9532004
TI  - Expression of bone morphogenetic proteins in salivary pleomorphic adenomas.
AB  - Salivary pleomorphic adenomas are often associated with chondroid tissue
      formation. We investigated the relationship between chondroid tissue formation
      and the expression of bone morphogenetic proteins (BMPs), which are strong
      inducers of ectopic bone and cartilage formation. Fifteen pleomorphic adenomas
      and seven normal salivary glands were examined genetically and
      immunohistochemically. Semiquantitative reverse transcription-polymerase chain
      reaction (RT-PCR) analysis showed that BMP-1, BMP-2, BMP-3, BMP-4, and BMP-7
      mRNAs were overexpressed in 10 (66.7%), 9 (60.0%), 1 (6.7%), 8 (53.3%), and 12
      (80.0%), respectively, of the 15 pleomorphic adenomas. Overexpression of BMP-2
      mRNA was observed in pleomorphic adenomas. Marked chondroid formation or
      expression of type II collagen was frequently observed in pleomorphic adenomas
      that overexpressed BMP-2 mRNA. Immunohistochemically, BMP-2 was detected in
      modified myoepithelial cells aroud chondroid tissue and basement membranes. These
      results suggest that BMPs, and expecially BMP-2, have a role in chondroid
      formation in pleomorphic adenomas.

PMID- 9532005
TI  - Spectrum of GCDFP-15 expression in human fetal and adult normal tissues.
AB  - GCDFP-15, a glycoprotein identified in the cyst fluid of cystic breast disease,
      is considered to be a marker of apocrine differentiation. Studies on GCDFP-15
      localization in adult normal tissues are lacking, and no information on GCDFP-15
      expression during fetal development has been reported. We investigated GCDFP-15
      expression in a large series of formalin-fixed, paraffin-embedded normal human
      adult and fetal tissues using the monoclonal antibody BRST-2. In normal adult
      tissues GCDFP-15 expression was found in all apocrine, lacrimal, ceruminous and
      Moll's glands and in numerous serous cells of the submandibular, sublingual and
      minor salivary glands. The serous cells of nasal and bronchial glands were also
      positive; parotid and laryngeal glands showed rare immunoreactive cells. GCDFP-15
      positive cells were observed in all cutaneous eccrine glands from different body
      sites. In fetal tissues immunoreactivity was observed in numerous acinous cells
      of all tracheal, bronchial and submandibular salivary glands. GCDFP-15 positivity
      was identified in numerous cells of all axillary sweat glands and in rare cells
      of some sweat glands of the thorax, abdomen, back, leg and arm. In both apocrine
      and nonapocrine glands GCDFP-15 was always localized in the secretory component.
      These data suggest that GCDFP-15 is a glandular differentiation marker associated
      with apocrine secretion; that it is expressed in glands that have phylogenetic
      origins in common with apocrine glands (submandibular salivary and submucosal
      bronchial glands); and that eccrine cutaneous glands express GCDFP-15 and thus
      might be referred to as mixed apocrine-eccrine glands. GCDFP-15 is expressed
      during fetal development and may represent a common marker of embryologically
      linked glandular structures.

PMID- 9532006
TI  - Immunopathological mechanisms underlying the time-course of Trichinella spiralis
      cardiomyopathy in rats.
AB  - The present study shows that isolated, perfused hearts from rats orally infected
      with Trichinella spiralis have a reduced left ventricular developed pressure
      (LVDP), heart rate (HR) and coronary flow (CF). This reduction is considerably
      enhanced by a single bolus (100 pM) of PAF (platelet activating factor, an
      eosinophil activator), especially at 21 days post-infection (d.p.i.), which is
      the time of the maximum increase in blood and tissue eosinophilia. Helminthic DNA
      analysis shows that, from 21 d.p.i. onwards, the morphological and functional
      changes in the myocardium cannot be ascribed to the parasite's presence, whereas
      its antigens and the attendant immunopathological reactions might have a role in
      the induction of myocardial damage and dysfunction. Some perivascular
      inflammatory cells (eosinophils and mast cells) appear to undergo degranulation.
      All these data suggest a complex sequence of events, from acute myocarditis (21
      d.p.i.) which may lead in time (48 d.p.i. onwards) to a dilating cardiomyopathy.

PMID- 9532007
TI  - Colocalization of collagen overexpression and inflammatory cell infiltration in
      the two-kidney one-clip rat model from the early days of hypertension onward.
AB  - In the first 6 days of hypertension, infiltrated mononuclear cells were
      colocalized with collagen (I) mRNA-overexpressing fibroblasts in the adventitial
      area of unclipped kidney. The number of adventitial infiltrated mononuclear cells
      was correlated with adventitial collagen (I) surface expansion. After 22 days of
      hypertension no collagen (I) mRNA-overexpressing fibroblasts or any increase in
      collagen area or mononuclear cell infiltration was observed. In the interstitium
      of unclipped kidney, collagen (I) mRNA overexpression, collagen (I) expansion and
      mononuclear cell infiltration began later, from the 7th day of hypertension, and
      kept increasing. In the clipped kidney, after expansion in the first 6 days of
      hypertension, the adventitial collagen remained stable. These results suggest
      that in the unclipped kidney fibroblastic activation begins within the first 6
      days of hypertension in the adventitial area, but is transient, and fibrosis then
      spreads in the interstitium. Mononuclear cell infiltration is colocalized and
      correlated with adventitial and interstitial fibrosis. In the first 6 days,
      hypertension is not the only cause of fibrosis; the same level of adventitial
      fibrosis is detected in the nonhypertensive clipped kidney. All observed
      pathological phenomena could be detected within the first 3 days of hypertension.

PMID- 9532008
TI  - Generation of a monoclonal antibody to P-glycoprotein peptides using tuberculin
      PPD as a carrier.
AB  - A novel immunization protocol together with stringent selection criteria have
      been employed to generate a new murine monoclonal antibody ("D8", isotype IgG1,
      kappa) which specifically recognizes the human p170 drug resistance glycoprotein.
      This antibody is directed towards a defined peptide sequence located in the -COOH
      terminal region of the first external loop of the molecule. It is reactive with
      its epitope within the intact native glycoprotein in formalin-fixed and
      conventionally processed histological tissues, in flow-cytometric preparations
      and by Western blotting. The antibody precipitates its target peptide sequence
      from solution, and thus may be a useful reagent with which to establish an ELISA,
      RIMA or other similar assay. The peptide epitope recognized by this monoclonal
      antibody is restricted to the human MDR1 gene product and is not contained within
      the rodent homologue of the P-170 molecule. Immunohistochemistry has consistently
      failed to detect this epitope in rodent tissues, thus confirming that it does not
      exhibit the cross-reactivity of other currently available anti-P-glycoprotein
      monoclonal antibodies. The experience of this study emphasizes the value of the
      tuberculin-PPD (purified protein derivative) immunization protocol as a powerful
      strategy when generating monoclonal antibodies to small synthetic peptides. The
      resulting monoclonal antibody (D8) will be an invaluable reagent with which to
      analyse P-170 glycoprotein expression when assessing the role of multidrug
      resistance in human cancers.

PMID- 9532009
TI  - Paget's disease versus Toker cell hyperplasia in a supernumerary nipple.
AB  - We report the second case of mammary Paget's disease arising in a supernumerary
      nipple of a 29-year-old woman. The epithelium of the nipple was infiltrated by
      large cells with abundant and pale-staining cytoplasm. The nuclei had a vesicular
      chromatin pattern and identifiable nucleoli. The cells were strongly
      immunoreactive with KL1, CEA and EMA, but did not show reactivity with PS100,
      HMB45, or erb-B2. The pathogenesis of Paget cells is unclear. In our case, the
      lesion showed nearly all the clinical, histological and histochemical
      characteristics of Paget's disease, though without involvement of mammary gland
      epithelium and underlying carcinoma. The possibility of an intraepidermal origin,
      either by transformation from epidermal keratinocytes or by derivation from
      intraepidermal precursor cells, has to be considered. The differential diagnosis
      against Toker cell hyperplasia is also discussed.

PMID- 9532010
TI  - Extranodal follicular dendritic cell tumour of the nasopharynx.
AB  - We report the first case of an extranodal follicular dendritic cell (FDC) tumour
      localized in the nasopharynx of a 44-year-old male patient. The tumour cells were
      characterized immunohistochemically by strong expression of CD21, HLA-DR and
      vimentin and focal expression of CD68 and cytokeratin. Electron microscopic
      examination revealed desmosomal cell junctions between adjacent cell processes.
      Molecular genetic analysis using polymerase chain reaction (PCR) showed germline
      configuration of immunoglobulin and T-cell receptor genes. Epstein-Barr virus
      (EBV) genomes were detectable by PCR. After complete surgical tumour removal and
      radiotherapy the patient is disease-free 20 months after the initial diagnosis.

PMID- 9532012
TI  - Techniques of pancreas transplantation through the world: an IPITA Center survey.

PMID- 9532011
TI  - Chondroma of the bladder.
AB  - This case report describes a chondroma of the bladder in a 63-year-old woman with
      clinical complaints of pain in the left fossa iliaca. The lesion was a tumour
      with a lobulated growth pattern composed of chondrocytes embedded in a chondroid
      matrix. Neither mitotic figures nor increased cellularity were present. Nuclei
      were inconspicuous. Immunohistochemical examination showed reactivity for S100
      and vimentin.

PMID- 9532013
TI  - Report of the International Pancreas Transplant Registry.

PMID- 9532014
TI  - Status of pancreatic transplantation with enteric drainage: 30 years world
      experience.

PMID- 9532015
TI  - Magnetic resonance imaging and Levovist-enhanced color and power Doppler imaging
      in the follow-up of pancreas transplants in patients after combined pancreas and
      kidney transplantation.

PMID- 9532016
TI  - Glucose tolerance and insulin sensitivity in pancreas transplant recipients:
      comparison of whole-organ and segmental transplantation.

PMID- 9532017
TI  - Immunologic risks of combined kidney-pancreas transplantation.

PMID- 9532018
TI  - Enteric versus bladder drainage in pancreas transplantation: initial experience
      at Niguarda Hospital, Milan.

PMID- 9532019
TI  - Early pancreas retransplantation for vascular thrombosis in simultaneous pancreas
      kidney transplants.

PMID- 9532020
TI  - Evaluation of arterial flow of pancreatic grafts with duplex-Doppler
      ultrasonography.

PMID- 9532021
TI  - Role of bench angiography in the assessment of pancreaticoduodenal graft blood
      supply.

PMID- 9532022
TI  - Pancreas transplant graft evaluation using the MIBI scan--a useful tool.

PMID- 9532023
TI  - Outcome analysis of hospital charges after simultaneous kidney-pancreas
      transplantation: influence of outliers on resource utilization.

PMID- 9532024
TI  - Ganciclovir/acyclovir and fluconazole prophylaxis after simultaneous kidney
      pancreas transplantation.

PMID- 9532025
TI  - Impact of intra-abdominal fluid collections following simultaneous pancreas
      kidney transplantation on graft and patient loss.

PMID- 9532026
TI  - Pancreas underutilization according to united network for organ sharing data.

PMID- 9532027
TI  - Hypotension after pancreatic reperfusion during combined kidney-pancreas
      transplantation.

PMID- 9532028
TI  - Histologic grading scheme for pancreas allograft rejection: application in the
      differential diagnosis from other pathologic entities.

PMID- 9532029
TI  - Long-term metabolic control in pancreas transplant patients according to three
      techniques.

PMID- 9532030
TI  - Synchronous pancreas-kidney transplantation with portal venous and enteric
      exocrine drainage: outcome in 70 consecutive cases.

PMID- 9532032
TI  - Assessment of function and survival as measures of renal graft outcome after
      kidney and kidney-pancreas transplants in type I diabetics.

PMID- 9532031
TI  - The effectiveness of a transplant out-patient unit as a cost-reducing strategy
      following pancreas transplantation.

PMID- 9532033
TI  - Complications and outcome of combined kidney-pancreas transplantation for end
      stage diabetic nephropathy: a retrospective single-center analysis. Leuven
      Collaborative Group for Transplantation.

PMID- 9532034
TI  - Donor factors affecting outcome after pancreas transplantation.
AB  - In this study, we demonstrated that Px grafts from donors older than 45 years are
      associated with an increased risk of developing poor glycemic control and
      premature loss of Px function. Previous studies corroborate our finding that age
      of the donor is the principal donor characteristic impacting postoperative Px
      survival. Whereas prior studies also implicated hyperamylasemia as a factor which
      contributes adversely to outcome, we were unable to demonstrate a significant
      influence of donor hyperamylasemia on long-term graft survival, although it did
      correlate with the degree of immediate postoperative pancreatitis and with the
      need for oral hypoglycemic agents. Similarly, elevated blood glucoses in the
      donor, which can be a result of many other factors unrelated to the quality of
      the graft, did not predict a poor outcome in the recipient. NHB donor pancreata
      did as well as HB pancreata with regards to all postoperative functional
      parameters. A marginally increased risk of developing major complications was
      associated with older donors. Despite the frequent use of non-ideal donors,
      including older and NHB donors, excellent overall Px graft survival can be
      achieved. Although the quality of the pancreas graft was not directly addressed
      in this study, we believe irrespective of hyperglycemia or hyperamylasemia,
      subjective assessment of organ quality by an experienced transplant surgeon is
      the most important determinant of suitability.

PMID- 9532035
TI  - Cost-utility analysis of pancreas transplantation compared to other treatment
      options for type I diabetics with end-stage renal disease.

PMID- 9532036
TI  - Insulin independence for more than 10 years in 32 pancreas transplant recipients
      from a historical era.

PMID- 9532037
TI  - Solitary pancreas transplants: a new era.

PMID- 9532038
TI  - Combined kidney and pancreas transplants from living donors.

PMID- 9532039
TI  - Analysis of mortality after pancreas transplantation.

PMID- 9532040
TI  - Delayed endocrine graft function: truth or myth?

PMID- 9532041
TI  - Efficacy of OKT3 as primary therapy for histologically confirmed acute renal
      allograft rejection in simultaneous kidney and pancreas transplant recipients.

PMID- 9532043
TI  - Graft failure after solitary pancreas transplantation.

PMID- 9532044
TI  - Long-term outcomes in simultaneous kidney-pancreas transplantation.

PMID- 9532045
TI  - Outcome of 300 consecutive pancreas-kidney transplants.

PMID- 9532042
TI  - Patterns of graft loss following simultaneous kidney-pancreas transplantation.

PMID- 9532046
TI  - Increased morbidity and mortality of simultaneous pancreas-renal transplantation
      in patients over 49 years of age.

PMID- 9532047
TI  - Surgical complications in 123 consecutive pancreas transplant recipients:
      comparison of bladder and enteric drainage.

PMID- 9532048
TI  - Simultaneous islet-liver transplantation: preliminary results from the UC Islet
      Transplantation Consortium.

PMID- 9532049
TI  - Long-term outcome of segmental duct injected pancreas: three to 13 years
      survival.

PMID- 9532050
TI  - Pancreas transplantation without antibody therapy.

PMID- 9532051
TI  - Assessment of viability of pancreas transplants from non-heart-beating cadaver.

PMID- 9532052
TI  - Inflammatory response after total pancreatectomy and islet autotransplantation.

PMID- 9532053
TI  - Initial experience with clinical islet transplantation in Argentina.

PMID- 9532054
TI  - Clinical islet transplantation after allogeneic orthotopic liver transplantation.

PMID- 9532055
TI  - Intraportal and splenic human islet autotransplantation combined with total
      pancreatectomy.

PMID- 9532056
TI  - Splenic human islet autotransplantation: anatomical variations of splenic venous
      drainage.

PMID- 9532057
TI  - Results of human islet allotransplantation in cystic fibrosis and type I diabetic
      patients.

PMID- 9532058
TI  - Insulin independence after allogeneic intraportal islet transplantation: relation
      to functional tests.

PMID- 9532059
TI  - Immediate insulin-independence after retransplantation of islets prepared from an
      allograft pancreatectomy in a type 1 diabetic patient.

PMID- 9532060
TI  - Studies of the impact of pancreas-kidney and kidney transplantation on peripheral
      nerve conduction in diabetic patients.

PMID- 9532061
TI  - Gal alpha(1,3)Gal expression on neonatal porcine islet cells and susceptibility
      to human antibody/complement lysis.

PMID- 9532062
TI  - Pattern of bone loss after simultaneous pancreas-kidney transplantation: a
      prospective study.

PMID- 9532064
TI  - Beneficial effect of fetal islet grafting on development of late diabetic
      complications.

PMID- 9532063
TI  - Pancreas transplantation versus islet transplantation versus insulin therapy in
      the prevention of nephropathy in alloxan-induced diabetic rats.

PMID- 9532065
TI  - A 10 year prospective study of IDDM patients subjected to combined pancreas and
      kidney transplantation or kidney transplantation alone.

PMID- 9532066
TI  - Sustained improvement in cardiac function 24 months following pancreas-kidney
      transplant.

PMID- 9532067
TI  - Efficacy of pancreatic transplantation on cardiovascular alterations in diabetic
      rats: an ultrastructural and immunohistochemical study.

PMID- 9532068
TI  - Effects of pancreas transplantation on quality of life in type I diabetic
      patients undergoing kidney transplantation.

PMID- 9532069
TI  - Endotoxin contamination of reagents used during isolation and purification of
      human pancreatic islets.

PMID- 9532071
TI  - A prospective comparison of discontinuous Euroficoll and Eurodextran gradients
      for islet purification.

PMID- 9532070
TI  - Sterile filtration of collagenase solution: effect of filter membrane composition
      on enzyme recovery.

PMID- 9532072
TI  - Effect of prophylactic administration of trypsin inhibitors in porcine pancreas
      islet isolation.

PMID- 9532073
TI  - Influence of human donor factors on pancreatic collagenase digestion.

PMID- 9532074
TI  - Extracellular matrix proteins in the porcine pancreas: a structural analysis for
      directed pancreatic islet isolation.

PMID- 9532075
TI  - Monitoring of enzymatic digestions on porcine pancreatic tissue using a simple
      histological assay.

PMID- 9532076
TI  - Improvement of adult porcine pancreatic islet isolation; employment of an
      innovative enzyme solution.

PMID- 9532077
TI  - Similar effect of enzymes on pig and rat islets.

PMID- 9532078
TI  - Intraductal collagenase delivery into the human pancreas using syringe loading or
      controlled perfusion.

PMID- 9532079
TI  - Porcine islet preservation during isolation in University of Wisconsin solution.

PMID- 9532080
TI  - No porcine islet loss during density gradient purification in a novel iodixanol
      in University of Wisconsin solution.

PMID- 9532081
TI  - Monitoring of insulin content during human islet isolation.

PMID- 9532082
TI  - The islet protective effect of beraprost sodium during collagenase digestion.

PMID- 9532083
TI  - Improved pig islet yield and post-culture recovery using Liberase PI purified
      enzyme blend.

PMID- 9532084
TI  - Identification of a pig strain with maximal islet mass.

PMID- 9532085
TI  - Purified murine islet allografts: islet engraftment as influenced by implantation
      site and glucotoxicity.

PMID- 9532086
TI  - Evaluation of islet isolation by a new automated method (Coulter Multisizer Ile)
      and manual counting.

PMID- 9532088
TI  - In vitro islet culture: development of a serum-free medium.

PMID- 9532087
TI  - Effects of coculture on viability of rat pancreatic islets.

PMID- 9532089
TI  - Permeability characteristics of isolated Brockmann bodies.

PMID- 9532090
TI  - Islet cryopreservation strategies: maintaining islet volume within tolerable
      limits during freezing.

PMID- 9532091
TI  - Effect of cryopreservation on canine islet insulin secretion as measured by
      amperometric techniques.

PMID- 9532092
TI  - Improved islet survival and in vitro function using small intestinal submucosa.

PMID- 9532093
TI  - Preparation and long-term culture of isolated human pancreatic islets.

PMID- 9532094
TI  - Improved function of porcine islets after long-term culture in methylcellulose
      matrix.

PMID- 9532095
TI  - Osmotic responses of isolated canine islets to novel cryoprotectants.

PMID- 9532097
TI  - Improvement of porcine islet culture with porcine serum.

PMID- 9532096
TI  - A marginal number of islets reverses diabetes in mice after overnight culture
      with beraprost sodium.

PMID- 9532098
TI  - Effects of nicotinamide on xenotransplantation.

PMID- 9532099
TI  - Pancreatic glucagon damages isolated human islet function.

PMID- 9532100
TI  - Intraportal vs kidney subcapsular site for human pancreatic islet
      transplantation.

PMID- 9532101
TI  - Experimental islet cell transplantation in rats: optimization of the
      transplantation site.

PMID- 9532102
TI  - Primary nonfunction is not caused by accelerated rejection after pig-to-rat islet
      transplantation.

PMID- 9532104
TI  - Pravastatin prevents primary nonfunction of canine islet autografts.

PMID- 9532103
TI  - Specific inhibition of macrophage-derived proinflammatory cytokine synthesis with
      a tetravalent guanylhydrazone CNI-1493 accelerates early islet graft function
      posttransplant.

PMID- 9532105
TI  - Effect of embolization of impure islets on liver histology and biochemical
      variables.

PMID- 9532106
TI  - Intraportal human islet autotransplantation: an immunohistochemical study of
      islets in situ.

PMID- 9532108
TI  - Coencapsulation of allogeneic islets with allogeneic Sertoli cells prolongs graft
      survival without systemic immunosuppression.

PMID- 9532107
TI  - Acceptance of intrahepatic islet allografts without immunosuppression in the
      limited strain combination of mice from C57BL/6 to BALB/c.

PMID- 9532109
TI  - No late failures of intraportal human islet autografts beyond 2 years.

PMID- 9532110
TI  - Pancreatic preservation in a multiorgan procurement procedure and
      transplantation.

PMID- 9532111
TI  - Venous graft thrombosis in clinical pancreas transplantation: options for a
      rescue treatment.

PMID- 9532112
TI  - Combined kidney and pancreas transplantation: one institution's experience.

PMID- 9532113
TI  - Comparison of bladder-drained segmental vs whole pancreatoduodenal transplants at
      a single institution.

PMID- 9532114
TI  - Should enteric drainage be used as a primary procedure instead of bladder
      drainage in clinical pancreas transplantation?

PMID- 9532115
TI  - Value of perioperative treatment with sandostatin after pancreas transplantation:
      a prospective randomized trial.

PMID- 9532116
TI  - Pancreas-kidney transplantation with urinary bladder and enteric exocrine
      diversion: seventy cases without anastomotic complications.

PMID- 9532117
TI  - Surgical complications after conversion from bladder to enteric drainage in
      pancreaticoduodenal transplantation.

PMID- 9532118
TI  - Primary enteric drainage of the pancreas revisited: a viable alternative to
      bladder drainage in simultaneous pancreas-kidney transplants.

PMID- 9532119
TI  - Enteric conversion of bladder-drained pancreas allografts: experience in 95
      patients.

PMID- 9532120
TI  - Experience with allograft pancreatectomy after pancreas transplantation.

PMID- 9532121
TI  - Experimental pancreas transplantation using a supercharged graft to ensure portal
      venous drainage with urinary exocrine diversion: a novel surgical approach.

PMID- 9532122
TI  - Solitary pancreas transplantation using the portal-enteric technique.

PMID- 9532123
TI  - Toward engineering skeletal muscle to release peptide hormone from the human pre
      proinsulin gene.

PMID- 9532124
TI  - Introduction of immunomodulatory genes into isolated pancreatic islets via
      biolistic particle bombardment.

PMID- 9532125
TI  - Stable transduction of human pancreatic adenocarcinoma cells, rat fibroblasts,
      and bone marrow-derived stem cells with recombinant adeno-associated virus
      containing the rat preproinsulin II gene.

PMID- 9532126
TI  - Expansion of functional adult porcine islet cells in vitro using purified laminin
      5.

PMID- 9532127
TI  - Adenoviral-mediated catalase gene transfer protects porcine and human islets in
      vitro against oxidative stress.

PMID- 9532128
TI  - Investigation of a large, commercially farmed rodent (Capybara) as a potential
      donor for pancreatic islet xenotransplantation.

PMID- 9532129
TI  - Differential effect of leflunomide on concordant xenogeneic islet graft rejection
      and recurrence of autoimmune diabetes.

PMID- 9532130
TI  - Biolistic bioengineering of pancreatic beta-cells with fluorescent green protein.

PMID- 9532131
TI  - Nonviral transfection of isolated islets of Langerhans.

PMID- 9532132
TI  - Successful gene transfer into murine pancreatic islets using polyamine
      transfection reagents.

PMID- 9532133
TI  - Transplantation of genetically engineered insulin-producing hepatocytes into
      immunoincompetent mice.

PMID- 9532134
TI  - Islet cell autoimmunity in NOD mice transgenic to HLA-DQ8 and lacking I-Ag7.

PMID- 9532135
TI  - Assessment of the in vivo function of pig islets encapsulated in uncoated
      alginate microspheres.

PMID- 9532136
TI  - Subcutaneous transplantation of rat islets into diabetic nude.

PMID- 9532137
TI  - Biological encapsulation as a new model for preservation of islets of Langerhans.

PMID- 9532138
TI  - Transplantation of allogeneic/xenogeneic pancreatic islets containing coherent
      microcapsules in adult pigs.

PMID- 9532139
TI  - An artificial transplantation site for pancreatic islets.

PMID- 9532140
TI  - A bio-artificial endocrine pancreas for the treatment of diabetes.

PMID- 9532141
TI  - Viability studies of agarose microencapsulated islets of Langerhans from dogs.

PMID- 9532142
TI  - Microencapsulation improves viability of islets from CSK miniature swine.

PMID- 9532143
TI  - Is it possible to use the standard alginate-PLL procedure for production of small
      capsules?

PMID- 9532144
TI  - Time course of the cellular reaction toward microencapsulated xenogeneic islets
      in the rat.

PMID- 9532145
TI  - Factors causing failure of islets in nonovergrown capsules.

PMID- 9532146
TI  - Application of agarose microcapsules to allo-islet transplantation in a canine
      model.

PMID- 9532147
TI  - Transplantation of microencapsulated syngeneic and xenogeneic (neonatal porcine)
      islets in nonobese diabetic mice.

PMID- 9532148
TI  - Factors in success and failure of microencapsulated pancreatic islets.

PMID- 9532149
TI  - First results with a quadruple therapy regimen including tacrolimus and
      mycophenolate mofetil in patients after combined pancreas and kidney
      transplantation.

PMID- 9532150
TI  - Effects of tacrolimus, mycophenolate mofetil, and cyclosporine microemulsion on
      rejection incidence in synchronous pancreas-kidney transplantation.

PMID- 9532151
TI  - Tacrolimus eliminates acute rejection as a major complication following
      simultaneous kidney and pancreas transplantation.

PMID- 9532152
TI  - Simultaneous pancreas/kidney transplantation: comparison of mycophenolate mofetil
      versus azathioprine.

PMID- 9532153
TI  - Cholesterol control: long-term benefit of pancreas-kidney transplantation with FK
      506 immunosuppression.

PMID- 9532154
TI  - Leflunomide-based immunosuppression for porcine islet xenotransplantation.

PMID- 9532155
TI  - Mycophenolate mofetil/tacrolimus/single-shot versus azathioprine/cyclosporine/ATG
      in pancreas-kidney transplantation: results of a prospective randomized single
      center study.

PMID- 9532156
TI  - Mycophenolate mofetil and tacrolimus for induction and maintenance therapy after
      pancreas transplantation.

PMID- 9532158
TI  - Pravastatin and low-dose cyclosporine treatment prevent islet allograft rejection
      in mice.

PMID- 9532157
TI  - Tacrolimus without antilymphocyte induction therapy prevents pancreas loss from
      rejection in 123 consecutive patients.
AB  - In this series, antilymphoid induction therapy did not appear to be necessary to
      prevent early graft loss from rejection. In addition, we have followed
      cytomegalovirus (CMV) antigenemia (pp65) for CMV infection. Although some
      patients developed a positive antigenemia in the seropositive to negative donor
      recipient combinations, only one patient had a prolonged febrile course for 1
      week.

PMID- 9532160
TI  - Benefits and risks of early antilymphocyte rescue in simultaneous kidney-pancreas
      transplant recipients.

PMID- 9532159
TI  - Metabolic effects of FK 506 (tacrolimus) versus cyclosporine in portally drained
      pancreas allografts.

PMID- 9532161
TI  - Comparison of azathioprine and mycophenolate mofetil in pancreas transplantation.

PMID- 9532162
TI  - Diabetogenic synergism in canine islet autografts from cyclosporine and steroids
      in combination.

PMID- 9532163
TI  - Recipient treatment with gadolinium chloride improves engraftment of isogeneic
      islets in the liver.

PMID- 9532164
TI  - Identification and morphology of rat islet allografts with dithizone after
      induction of donor-specific transplant tolerance by intrathymic administration of
      soluble antigen alloantigens.

PMID- 9532166
TI  - Higher percentage of donor CD 34+ expression in peripheral blood of simultaneous
      pancreas/kidney/donor bone marrow versus than kidney/islet cell/donor bone marrow
      recipients.

PMID- 9532165
TI  - Prolongation of allograft survival of transfected islets expressing human CTLA4
      Ig, human soluble Fas ligand or a combination of the two.

PMID- 9532167
TI  - Immunosuppressive effects of synthetic derivative of genistein on the survival of
      pancreatic islet allografts.

PMID- 9532168
TI  - Fas ligand expression on islets as well as multiple cell lines results in
      accelerated neutrophilic rejection.

PMID- 9532169
TI  - Ischemia due to vascular rejection causes islet loss after pancreas
      transplantation.

PMID- 9532170
TI  - Prevention of diabetes recurrence after syngeneic islet transplantation in NOD
      mice by analogues of 1,25(OH)2D3 in combination with cyclosporin A: mechanism of
      action involves an immune shift from Th1 to Th2.

PMID- 9532171
TI  - Oral tolerance and allografts: can multiple oral administrations of low doses of
      highly purified islets induce peripheral tolerance in pancreatic islet
      allografts?

PMID- 9532172
TI  - Difference in immunologic responses between pancreatic and islet transplantation
      in "low responder" rat combinations with class I MHC disparity.

PMID- 9532174
TI  - Establishment of a method for analysis of chimerism in a baboon model (Papio
      hamadryas) of islet/bone marrow transplantation.

PMID- 9532173
TI  - Induction of unresponsiveness to islet xenografts by a short-course treatment by
      anti-CD4 nondepleting monoclonal antibody.

PMID- 9532175
TI  - A prediabetic model in the biobreeding Worcester rat.

PMID- 9532177
TI  - Normoglycemic environment is important for the growth and function of islet
      isografts.

PMID- 9532176
TI  - Islet cell autoimmunity in NOD mice transgenic for HLA-DQ8 and lacking I-Ag7.

PMID- 9532179
TI  - Assessment of oxidative stress in a pancreatic warm ischemia-reperfusion model.

PMID- 9532178
TI  - Acridine-orange uptake: new method to evaluate effects of organ preservation on
      viability of pancreatic grafts in the pig model.

PMID- 9532180
TI  - Mixed endo-exo ultrastructural morphology of some beta cells in adult porcine
      pancreas.

PMID- 9532182
TI  - Timing of insulin therapy for diabetic recipients with islet transplantation.

PMID- 9532181
TI  - Sensitivity of porcine islet beta cells to the diabetogenic action of
      streptozotocin.

PMID- 9532183
TI  - Variable responses of islet cells of different ages and species to hypoxia.

PMID- 9532184
TI  - Cellular immune response in the liver of mice rejecting intrahepatic rat and
      guinea pig islet xenografts: expansion of intermediate TCR cells.

PMID- 9532185
TI  - Haemodynamic profiles of hepato-coeliac arterial reconstruction in porcine
      segmental pancreatic autotransplantation.

PMID- 9532186
TI  - Glucose-induced activity of liver-type pyruvate kinase promoter in primary rat
      hepatocytes.

PMID- 9532187
TI  - Xenograft rejection of fetal porcine islet-like cell clusters in normal, T-cell
      receptor beta-, delta-, beta x delta-; perforin-; or granzyme B-deficient mice.

PMID- 9532188
TI  - No correlation between in vitro and in vivo function of human islets.

PMID- 9532189
TI  - Effect of gene gun-mediated CTLA4IG and Fas ligand gene transfection on
      concordant xenogeneic islet graft rejection.

PMID- 9532190
TI  - Evaluation of a purified enzyme blend for the recovery and in vitro function of
      isolated canine islets.

PMID- 9532191
TI  - In vitro amylase release: a simple test to assess the viability of pancreatic
      grafts during preservation.

PMID- 9532192
TI  - Transplantation of feline islets of Langerhans in the subretinal space of cat
      eyes.

PMID- 9532193
TI  - Photodynamic therapy can selectively eradicate pancreas exocrine secretion.

PMID- 9532194
TI  - Growth and differentiation of transplanted porcine neonatal pancreatic cell
      clusters in normal nude mice.

PMID- 9532195
TI  - Requirements for the beneficial effect of long-term incubation with growth
      hormone on insulin secretion from isolated human fetal islets.

PMID- 9532196
TI  - Determinants of the inhibitory effect of glucose toxicity on growth hormone
      induced improvement of insulin secretion from isolated human fetal islets.

PMID- 9532197
TI  - Effects of high or low dose of streptozocin on pancreatic islets in C57BL/6 and
      C.B17-SCID mice.

PMID- 9532198
TI  - Effects of monensin on insulin release from isolated human islets.

PMID- 9532199
TI  - Similar insulinotropic effects of alpha- and beta-D-glucose anomers on isolated
      large mammal and human islets.

PMID- 9532200
TI  - Insulin secretion in IDDM patients who have undergone successful pancreas-kidney
      transplantation.

PMID- 9532201
TI  - Hemipancreatectomy and systemic diversion of pancreatic venous drainage lead to
      independent alterations in the determinants of glucose tolerance in dogs.

PMID- 9532202
TI  - Quantification of tilapia islets: a direct relationship between islet cell number
      and body mass.

PMID- 9532203
TI  - Insulin secretory capacity and peripheral sensitivity after pancreas-kidney
      transplantation estimated by CIGMA.

PMID- 9532204
TI  - Insulin deficiency and increased intact and 32/33 split proinsulin secretion
      following human islet autotransplantation.

PMID- 9532205
TI  - Study of I-arginine: no pathway before and after low-dose Escherichia coli
      lipopolysaccharide in normal, diabetic, and islet transplanted rats.

PMID- 9532206
TI  - Surgical and chemical approaches to regulate hyperinsulinemia after pancreas
      transplantation in rats.

PMID- 9532207
TI  - Metabolic and immunohistochemical assessment of endocrine pancreatic function
      after orthotopic multivisceral transplantation.

PMID- 9532208
TI  - Long-term metabolic control in recipients of segmental or whole-organ pancreatic
      grafts with enteric exocrine diversion and function beyond 5 years.

PMID- 9532209
TI  - Induction of mild hypoglycemia by islet transplantation to the pancreas.

PMID- 9532210
TI  - Influence of hyperinsulinemia on lipoproteins after pancreas transplantation with
      systemic insulin drainage.
AB  - Successful pancreas transplantation with systemic drainage is followed by a
      normalization of carbohydrate and lipid metabolism with low levels of plasma
      cholesterol and triglycerides. HDL cholesterol concentration and CETP plasma
      levels were found to be increased and the composition of lipoproteins altered in
      that LDL and HDL2/HDL3 were enriched in UC, HDL2 enriched in PL, and LDL depleted
      in PL. The mechanisms by which hyperinsulinemia may cause the observed changes in
      surface composition of plasma lipoproteins are unknown, as is their clinical
      relevance. It remains to be seen whether these changes counterbalance the
      favorable effects of an increased triglyceride clearance capacity on the
      cardiovascular risk of diabetic patients.

PMID- 9532211
TI  - Is the high level of nitric oxide metabolites a marker in early rejection after
      experimental islet pancreas transplantation?

PMID- 9532212
TI  - Portal vein immunosuppressant levels and islet graft toxicity.

PMID- 9532213
TI  - Significance of pancreas graft biopsy in detection of rejection.

PMID- 9532214
TI  - Serum lipase as a marker for pancreatic allograft rejection.

PMID- 9532215
TI  - Late acute rejection after pancreas transplantation.

PMID- 9532216
TI  - Development of diagnostic markers for islet allograft rejection.

PMID- 9532217
TI  - Cardiorespiratory fitness in pancreas-kidney transplant recipients.

PMID- 9532218
TI  - Studies of gliotoxin in islet xenotransplantation.

PMID- 9532219
TI  - Neonatal porcine islet xenografts in nonobese diabetic mice: effects on blood
      glucose and analysis of cytokines expressed in the islet grafts.

PMID- 9532220
TI  - Collagenase digestion of the pig pancreas modifies the expression of Gal alpha 1
      3Gal, Pk, and Thomsen-Friedenreich antigens on adult porcine islets.

PMID- 9532221
TI  - G-cells in regenerating adult pancreatic tissue after pancreatic fragment
      autotransplantation in dog spleens.

PMID- 9532222
TI  - IA-2 antibodies are only positive in association with GAD 65 and islet cell
      antibodies in islet transplanted insulin-dependent diabetes mellitus patients.

PMID- 9532223
TI  - Tacrolimus-related microangiopathy in kidney and simultaneous pancreas-kidney
      recipients: evidence of endothelin and cytokine involvement.

PMID- 9532224
TI  - Islet toxicity of FK506 measured in canine autografts.

PMID- 9532225
TI  - Examination of microbiological contamination rates following bacterial culture
      and incubation for 2, 7, and 14 days.

PMID- 9532226
TI  - Distribution of alpha and beta cells in pancreas allograft biopsies: correlation
      with rejection and other pathologic processes.

PMID- 9532227
TI  - [Gastrointestinal complaints. Functional and organic causes].

PMID- 9532228
TI  - [Alpha-lipoic acid in diabetic neuropathy. Action mechanism and therapy. Clinical
      picture and pathogenesis of diabetic neuropathy].

PMID- 9532229
TI  - [Cost-effectiveness analysis of drugs].

PMID- 9532230
TI  - [Parkinson diseases--polyvalent therapy with Budipin].

PMID- 9532231
TI  - [Dementia-related diseases. Propentofyllin--a neuroprotective glia cell
      modulator].

PMID- 9532232
TI  - [Biphosphonate: osteoporosis-related fractures can be avoided].

PMID- 9532233
TI  - Structural basis for the pathophysiology of lipoprotein(a) in the athero
      thrombotic process.
AB  - Lipoprotein Lp(a) is a major and independent genetic risk factor for
      atherosclerosis and cardiovascular disease. The essential difference between
      Lp(a) and low density lipoproteins (LDL) is apolipoprotein apo(a), a glycoprotein
      structurally similar to plasminogen, the precursor of plasmin, the fibrinolytic
      enzyme. This structural homology endows Lp(a) with the capacity to bind to fibrin
      and to membrane proteins of endothelial cells and monocytes, and thereby to
      inhibit plasminogen binding and plasmin generation. The inhibition of plasmin
      generation and the accumulation of Lp(a) on the surface of fibrin and cell
      membranes favor fibrin and cholesterol deposition at sites of vascular injury.
      Moreover, insufficient activation of TGF-beta due to low plasmin activity may
      result in migration and proliferation of smooth muscle cells into the vascular
      intima. These mechanisms may constitute the basis of the athero-thrombogenic mode
      of action of Lp(a). It is currently accepted that this effect of Lp(a) is linked
      to its concentration in plasma. An inverse relationship between Lp(a)
      concentration and apo(a) isoform size, which is under genetic control, has been
      documented. Recently, it has been shown that inhibition of plasminogen binding to
      fibrin by apo(a) is also inversely associated with isoform size. Specific point
      mutations may also affect the lysine-binding function of apo(a). These results
      support the existence of functional heterogeneity in apolipoprotein(a) isoforms
      and suggest that the predictive value of Lp(a) as a risk factor for vascular
      occlusive disease would depend on the relative concentration of the isoform with
      the highest affinity for fibrin.

PMID- 9532234
TI  - pH titration of native and unfolded beta-trypsin: evaluation of the delta delta
      G0 titration and the carboxyl pK values.
AB  - The stabilizing free energy of beta-trypsin was determined by hydrogen ion
      titration. In the pH range from 3.0 to 7.0, the change in free energy difference
      for the stabilization of the native protein relative to the unfolded one (delta
      delta G0 titration) was 9.51 +/- 0.06 kcal/mol. An isoelectric point of 10.0 was
      determined, allowing us to calculate the Tanford and Kirkwood electrostatic
      factor w. This factor presented a nonlinear behavior and indicated more than one
      type of titratable carboxyl groups in beta-trypsin. In fact, one class of
      carboxyl group with a pK = 3.91 +/- 0.01 and another one with a pK = 4.63 +/-
      0.03 were also found by hydrogen ion titration of the protein in the folded
      state.

PMID- 9532235
TI  - Apolipoprotein and lipid abnormalities in chronic liver failure.
AB  - Total serum lipids, as well as apolipoproteins A-I (apo A-I) and B (apo B), were
      determined in 74 patients with chronic liver failure without cholestasis and in
      82 normal subjects. The VLDL, LDL and HDL lipid fractions were reduced in the
      liver failure group by 36%, 24% and 46%, respectively (P < 0.001).
      Apolipoproteins A-I and B were also reduced by 26% and 25%, respectively (P <
      0.001). However, the reduction of HDL cholesterol (HDLc) was more pronounced than
      that of apo A-I and the HDLc:apo A-I ratio was significantly lower in the liver
      failure group. After separating these patients into groups with plasma albumin
      lower than 3.0, between 3.0 and 3.5, and higher than 3.5 g/dl, the HDLc:apo A-I
      ratio was proportional to plasma albumin, but the correlation was not
      statistically significant. When these patients were separated by the Child
      classification of liver function, there was a correlation between the HDLc:apo A
      I ratio and liver function. The differences in the HDLc:apo A-I ratio between the
      Child groups B and C, and A and C were statistically significant (P < 0.05). We
      conclude that there is a more pronounced reduction in HDL cholesterol than in apo
      A-I in liver failure patients. Therefore, the HDLc:apo A-I ratio is a marker of
      liver function, probably because there is a decreased lecithin-cholesterol
      acyltransferase production by the diseased liver.

PMID- 9532236
TI  - Detection of cytotoxic activity on Vero cells in clinical isolates of Serratia
      marcescens.
AB  - Cytotoxin production was studied in 60 Serratia marcescens strains isolated from
      hospitalized patients. Association of cytotoxic activity with serotype, source of
      isolation and presence of plasmids was also evaluated. Thirteen of the 60 S.
      marcescens strains produced a cytotoxic effect on Vero cells. These strains were
      isolated from distinct clinical sources and classified into seven different
      serotypes (O1:H7; O4:NM; O10:NT; O19:NM; O6,14:H4; O6,14:NM and O6,14:H1). No
      relationship was observed between cytotoxic activity and clinical source or
      serotypes of the strains. Plasmids from five cytotoxin-producing S. marcescens
      strains were transferred to E. coli K12/711. The transconjugants did not exhibit
      cytotoxicity, indicating that the cytotoxic effect is not plasmid-mediated among
      these strains. Although a cytotoxic activity was demonstrated in filtrates of
      some S. marcescens strains, further studies should be performed to assess the
      role of this toxin in pathogenesis.

PMID- 9532237
TI  - Conditioned medium from activated spleen cells supports the survival of rat
      retinal cells in vitro.
AB  - Cytokines are a heterogeneous group of molecules that have been associated with
      several functions in the nervous system, such as survival and differentiation of
      neuronal and glial cells. In the present study, we demonstrated that conditioned
      medium from spleen cells activated with concanavalin A increased neuritogenesis
      and survival of retinal cells, as measured by biochemical and morphological
      criteria. Our data showed that conditioned medium induced a five-fold increase in
      the amount of protein after 120 h in vitro. This effect was not inhibited by the
      blockade of voltage-dependent L-type calcium channels with 5.0 microM nifedipine.
      However, the use of an intracellular calcium chelator (15.0 microM BAPTA-AM)
      inhibited this effect. Our results support the idea that factors secreted by
      activated lymphocytes, such as cytokines, can modulate the maintenance and the
      differentiation of rat retinal cells in vitro, indicating a possible role of
      these molecules in the development of retinal cells, as well as in its protection
      against pathological conditions.

PMID- 9532238
TI  - Molecular mimicry between cardiac myosin and Trypanosoma cruzi antigen B13:
      identification of a B13-driven human T cell clone that recognizes cardiac myosin.
AB  - Previous reports from our group have demonstrated the association of molecular
      mimicry between cardiac myosin and the immunodominant Trypanosoma cruzi protein
      B13 with chronic Chagas' disease cardiomyopathy at both the antibody and heart
      infiltrating T cell level. At the peripheral blood level, we observed no
      difference in primary proliferative responses to T. cruzi B13 protein between
      chronic Chagas' cardiopathy patients, asymptomatic chagasics and normal
      individuals. In the present study, we investigated whether T cells sensitized by
      T. cruzi B13 protein respond to cardiac myosin. T cell clones generated from a
      B13-stimulated T cell line obtained from peripheral blood of a B13-responsive
      normal donor were tested for proliferation against B13 protein and human cardiac
      myosin. The results showed that one clone responded to B13 protein alone and the
      clone FA46, displaying the highest stimulation index to B13 protein (SI = 25.7),
      also recognized cardiac myosin. These data show that B13 and cardiac myosin share
      epitopes at the T cell level and that sensitization of a T cell with B13 protein
      results in response to cardiac myosin. It can be hypothesized that this also
      occurs in vivo during T. cruzi infection which results in heart tissue damage in
      chronic Chagas' disease cardiomyopathy.

PMID- 9532239
TI  - Rabies infection and specific effect of vaccination in mice selected for high and
      low immunobiological parameters.
AB  - Innate and acquired resistance to rabies infection was investigated in mice
      genetically selected for high (H) or low (L) antibody responsiveness from
      selections I, III and IV and in mice selected for maximal (AIRmax) or minimal
      (AIRmin) acute inflammatory reaction. These mouse lines were infected
      intramuscularly with different virus dilutions and the LD50 was determined. The
      HIII and HIV mouse lines were more susceptible than the LIII and LIV lines and
      the HI line showed a discrete but higher resistance than the LI line. Analysis of
      the interline (H x L) F1 hybrids from selections III and IV indicated different
      dominance effects on the "resistant" and "susceptible" phenotypes when the route
      of vaccination was changed. No differences were observed between the AIRmax and
      AIRmin mice, suggesting that inflammation plays a minor role in the resistance to
      rabies virus. The comparison of LD50 in mice vaccinated by distinct routes showed
      that the highest interline difference occurred after intramuscular vaccination
      (250-fold between H and L and 800-fold between F1 and L). These results indicate
      that different mechanisms may participate in acquired antirabies resistance.

PMID- 9532240
TI  - Distribution of calcium-binding proteins in the chick visual system.
AB  - The calcium-binding proteins calbindin (CB), calretinin (CR), and parvalbumin
      (PV) have been extensively studied over the last decade since they appear to be
      important as buffers of intracellular calcium. In the present study we
      investigated the distribution of these proteins in the chick visual system by
      means of conventional immunocytochemistry. The results indicated that CB, CR, and
      PV are widely distributed in retinorecipient areas of the chick brain. In some
      regions, all three calcium-binding proteins were present at different intensities
      and often in different neurons such as in the dorsolateral thalamic complex. In
      other areas, such as the nucleus geniculatus lateralis ventralis, only CB and CR
      were detected, whereas PV was absent. These results show that these three calcium
      binding proteins are differentially distributed in the visual system of the
      chick, with varying degrees of co-localization.

PMID- 9532241
TI  - Glass pipette-carbon fiber microelectrodes for evoked potential recordings.
AB  - Current methods for recording field potentials with tungsten electrodes make it
      virtually impossible to use the same recording electrode also as a lesioning
      electrode, for example for histological confirmation of the recorded site,
      because the lesioning procedure usually wears off the tungsten tip. Therefore,
      the electrode would have to be replaced after each lesioning procedure, which is
      a very high cost solution to the problem. We present here a low cost, easy to
      make, high quality glass pipette-carbon fiber microelectrode that shows
      resistive, signal/noise and electrochemical coupling advantages over tungsten
      electrodes. Also, currently used carbon fiber microelectrodes often show problems
      with electrical continuity, especially regarding electrochemical applications
      using a carbon-powder/resin mixture, with consequent low performance, besides the
      inconvenience of handling such a mixture. We propose here a new method for
      manufacturing glass pipette-carbon fiber microelectrodes with several advantages
      when recording intracerebral field potentials.

PMID- 9532242
TI  - Study of the embryofeto-toxicity of Crown-of-Thorns (Euphorbia milii) latex, a
      natural molluscicide.
AB  - The crude latex of Crown-of-Thorns (Euphorbia milii var. hislopii) is a potent
      plant molluscicide and a promising alternative to the synthetic molluscicides
      used in schistosomiasis control. The present study was undertaken to investigate
      the embryofeto-toxic potential of E. milii latex. The study is part of a
      comprehensive safety evaluation of this plant molluscicide. Lyophilized latex (0,
      125, 250 and 500 mg/kg body weight) in corn oil was given by gavage to Wistar
      rats (N = 100) from days 6 to 15 of pregnancy and cesarean sections were
      performed on day 21 of pregnancy. The numbers of implantation sites, living and
      dead fetuses, resorptions and corpora lutea were recorded. Fetuses were weighed,
      examined for external malformations, and fixed for visceral examination, or
      cleared and stained with Alizarin red S for skeleton evaluation. A reduction of
      body weight minus uterine weight at term indicated that E. milii latex was
      maternally toxic over the dose range tested. No latex-induced embryolethality was
      noted at the lowest dose (125 mg/kg) but the resorption rate was markedly
      increased at 250 mg/kg (62.5%) and 500 mg/kg (93.4%). A higher frequency of
      fetuses showing signs of delayed ossification (control: 17.4%; 125 mg/kg: 27.4%
      and 250 mg/kg: 62.8%; P < 0.05 vs control) indicated that fetal growth was
      retarded at doses > or = 125 mg latex/kg body weight. No increase in the
      proportion of fetuses with skeletal anomalies was observed at the lowest dose but
      the incidence of minor skeletal malformations was higher at 250 mg/kg body weight
      (control: 13.7%; 125 mg/kg: 14.8%; 250 mg/kg: 45.7%; P < 0.05 vs control). Since
      a higher frequency of minor malformations was noted only at very high doses of
      latex which are embryolethal and maternally toxic, it is reasonable to conclude
      that this plant molluscicide poses no teratogenic hazard or, at least, that this
      possibility is of a considerably low order of magnitude.

PMID- 9532244
TI  - Effect of trolox C on cardiac contracture induced by hydrogen peroxide.
AB  - Hydrogen peroxide (H2O2) perfused into the aorta of the isolated rat heart
      induces a positive inotropic effect, with cardiac arrhythmia such as
      extrasystolic potentiation or cardiac contractures, depending on the dose. The
      last effect is similar to the "stone heart" observed in reperfusion injury and
      may be ascribed to lipoperoxidation (LPO) of the membrane lipids, to protein
      damage, to reduction of the ATP level, to enzymatic alterations and to
      cardioactive compounds liberated by LPO. These effects may result in calcium
      overload of the cardiac fibers and contracture ("stone heart"). Hearts from male
      Wistar rats (300-350 g) were perfused at 31 degrees C with Tyrode, 0.2 mM trolox
      C, 256 mM H2O2 or trolox C + H2O2. Cardiac contractures (baseline elevation of
      the myograms obtained) were observed when hearts were perfused with H2O2 (Tyrode:
      5.9 +/- 3.2; H2O2: 60.5 +/- 13.9% of the initial value); perfusion with H2O2
      increased the LPO of rat heart homogenates measured by chemiluminescence (Tyrode:
      3,199 +/- 259; H2O2: 5,304 +/- 133 cps mg protein-1 60 min-1), oxygen uptake
      (Tyrode: 0.44 +/- 0.1; H2O2: 3.2 +/- 0.8 nmol min-1 mg protein-1) and
      malonaldehyde (TBARS) formation (Tyrode: 0.12 +/- 0; H2O2: 0.37 +/- 0.1 nmol/ml).
      Previous perfusion with 0.2 mM trolox C reduced the LPO (chemiluminescence: 4,098
      +/- 531), oxygen uptake (0.51 +/- 0) and TBARS (0.13 +/- 0) but did not prevent
      the H2O2-induced contractures (33.3 +/- 16%). ATP (Tyrode: 2.84 +/- 0; H2O2: 0.57
      +/- 0) and glycogen levels (Tyrode: 0.46 +/- 0; H2O2: 0.26 +/- 0) were reduced by
      H2O2. Trolox did not prevent these effects (ATP: 0.84 +/- 0 and glycogen: 0.27 +/
      0). Trolox C is known to be more effective than alpha-tocopherol or gamma
      tocopherol in reducing LPO though it lacks the phytol portion of vitamin E to be
      fixed to the cell membranes. Trolox C, unlike vitamin A, did not prevent the
      glycogen reduction induced by H2O2. Trolox C induced a positive chronotropic
      effect that resulted in higher energy consumption. The reduction of energy level
      seemed to be more important than LPO in the mechanism of H2O2-induced
      contracture.

PMID- 9532243
TI  - Application of various antioxidants in the treatment of influenza.
AB  - We determined the effect of the antioxidants superoxide dismutase,
      desferrioxamine and allopurinol on the survival of male CBA mice infected
      intranasally with 2-5 LD50 lung influenza virus A/Aichi/2/68. Survival for at
      least 20 days was observed for 45% of the mice that received 1000 U/day
      superoxide dismutase prepared from red blood cells on days 5, 6, 7 and 8 after
      infection, and 75% survival was observed for mice that received the same dose on
      days 4, 5, 6, 7 and 8. Desferrioxamine, 25 mg/kg per day and 100 mg/kg per day
      injected subcutaneously, resulted in survival rates of 5 and 0%, respectively,
      compared to 10% survival observed for saline-injected controls. Allopurinol at
      doses of 5 to 50 mg/kg per day had no effect on mouse survival. These data
      demonstrate the efficacy of superoxide dismutase for the protection of mice
      against hemorrhagic lung edema. The ineffectiveness of allopurinol suggests that
      the xanthine oxidase system does not play a major role in hemorrhage or lung
      edema and that caution is necessary when desferrioxamine is administered during
      an acute inflammatory process accompanied by erythrocyte lysis.

PMID- 9532245
TI  - Vitamin D3-induced calcemic and phosphatemic responses in the freshwater mud eel
      Amphipnous cuchia maintained in different calcium environments.
AB  - Vitamin D3 (100 ng 100 g body weight-1 day-1) was administered intraperitoneally
      (i.p.) to the freshwater mud eel Amphipnous cuchia kept in artificial freshwater,
      calcium-free freshwater, low-calcium freshwater (0.2 mmol/l CaCl2) or calcium
      rich freshwater (13.4 mmol/l CaCl2) for 15 days. Analyses of serum calcium and
      phosphate levels were performed on days 1, 3, 5, 10 and 15 after the beginning of
      the experiment (six eels from each group at each interval). Administration of
      vitamin D3 elevated the serum calcium [maximum elevation occurred at day 10 in
      artificial freshwater (vehicle: 10.55 +/- 0.298, vitamin D: 13.90 +/- 0.324), low
      calcium freshwater (vehicle: 11.17 +/- 0.220, vitamin D: 12.98 +/- 0.297) and
      calcium-rich freshwater (vehicle: 11.24 +/- 0.373, vitamin D: 14.24 +/- 0.208)
      whereas it occurred at day 5 (vehicle: 8.42 +/- 0.253, vitamin D: 11.07 +/-
      0.328) in calcium-free freshwater] and phosphate levels [maximum elevation at day
      15 in artificial freshwater (vehicle: 4.39 +/- 0.105, vitamin D: 5.37 +/- 0.121),
      calcium-free freshwater (vehicle: 4.25 +/- 0.193, vitamin D: 5.12 +/- 0.181), low
      calcium freshwater (vehicle: 3.93 +/- 0.199, vitamin D: 5.28 +/- 0.164) and
      calcium-rich freshwater (vehicle: 3.77 +/- 0.125, vitamin D: 5.46 +/- 0.151)] of
      the fish maintained in the above mentioned environmental media, but the responses
      were more pronounced in the fish kept in calcium-rich media.

PMID- 9532246
TI  - Outward potassium current oscillations in macrophage polykaryons: extracellular
      calcium entry and calcium-induced calcium release.
AB  - Outward current oscillations associated with transient membrane
      hyperpolarizations were induced in murine macrophage polykaryons by membrane
      depolarization in the absence of external Na+. Oscillations corresponded to a
      cyclic activation of Ca(2+)-dependent K+ currents (IKCa) probably correlated with
      variations in intracellular Ca2+ concentration. Addition of external Na+ (8 mM)
      immediately abolished the outward current oscillations, suggesting that the
      absence of the cation is necessary not only for their induction but also for
      their maintenance. Oscillations were completely blocked by nisoldipine. Ruthenium
      red and ryanodine reduced the number of outward current cycles in each episode,
      whereas quercetin prolonged the hyperpolarization 2- to 15-fold. Neither low
      molecular weight heparin nor the absence of a Na+ gradient across the membrane
      had any influence on oscillations. The evidence suggests that Ca2+ entry through
      a pathway sensitive to Ca2+ channel blockers is elicited by membrane
      depolarization in Na(+)-free medium and is essential to initiate oscillations,
      which are also dependent on the cyclic release of Ca2+ from intracellular Ca(2+)
      sensitive stores; Ca2+ ATPase acts by reducing intracellular Ca2+, thus allowing
      slow deactivation of IKCa. Evidence is presented that neither a Na+/Ca2+
      antiporter nor Ca2+ release from IP3-sensitive Ca2+ stores participate directly
      in the mechanism of oscillation.

PMID- 9532247
TI  - Plasma cortisol levels in captive wild felines after chemical restraint.
AB  - Eight Panthera onca (Po), 13 Felis concolor (Fc), 7 Felis yagouaroundi (Fy), 7
      Felis tigrina (Ft) and 5 Felis pardalis (Fp) specimens from Sao Paulo State zoos
      were used. All animals were restrained with darts containing 10 mg/kg ketamine
      and 1 mg/kg xylazine. Venous blood samples were collected as soon as possible
      (within 15-20 min) and serum was frozen until the time for cortisol
      quantification. Cortisol was determined using a solid phase radioimmunoassay with
      an intra-assay coefficient of 8.51%. Data were analyzed statistically by the
      Kruskal-Wallis test, followed by Dunn's multiple comparisons test, and the one
      sample t-test, with the level of significance set at P < 0.05. Data are reported
      as means +/- SEM. Cortisol levels differed among the captive felines: Po = 166 +/
      33a, Fc = 670 +/- 118b, Fy = 480 +/- 83b, Ft = 237 +/- 42ab, Fp = 97 +/- 12a
      nmol/l (values followed by different superscript letters were significantly
      different (P < 0.001)). Since most of the veterinary procedures on these species
      involve chemical restraint, these results show the necessity of preventive
      measures in order to minimize the effect of restraint stress on more susceptible
      species.

PMID- 9532248
TI  - Gastric emptying of liquids in rats dehydrated by water deprivation.
AB  - The gastric emptying of liquids was investigated in male Wistar rats (8 to 10
      weeks old, 210-300 g) dehydrated by water deprivation. In this model of
      dehydration, weight loss, hematocrit and plasma density were significantly higher
      in the dehydrated animals than in the control groups after 48 and 72 h of water
      deprivation (P < 0.05). Three test meals (saline (N = 10), water (N = 10) and a
      WHO rehydrating solution containing in one liter 90 mEq sodium, 20 mEq potassium,
      80 mEq chloride and 30 mEq citrate (N = 10)) were used to study gastric emptying
      following water deprivation for 24, 48 and 72 h. After 72 h, gastric emptying of
      the water (39.4% retention) and rehydrating solution (49.2% retention) test meals
      was significantly retarded compared to the corresponding control groups (P <
      0.05, Mann-Whitney test). The 72-h period of deprivation was used to study the
      recovery from dehydration, and water was supplied for 60 or 120 min after 67 h of
      deprivation. Body weight loss, hematocrit and plasma density tended to return to
      normal when water was offered for 120 min. In the animals supplied with water for
      60 min, there was a recovery in the gastric emptying of water while the gastric
      emptying of the rehydrating solution was still retarded (53.1% retention; P <
      0.02, Kruskal-Wallis test). In the group supplied with water for 120 min, the
      gastric emptying of the rehydrating (51.7% retention) and gluco-saline (46.0%
      retention) solutions tended to be retarded (P = 0.04, Kruskal-Wallis test). In
      this model of dehydration caused by water deprivation, with little alteration in
      the body electrolyte content, gastric emptying of the rehydrating solution was
      retarded after rehydration with water. We conclude that the mechanisms whereby
      receptors in the duodenal mucosa can modify gastric motility are altered during
      dehydration caused by water deprivation.

PMID- 9532249
TI  - Cardiovascular and respiratory changes during slow-wave sleep in rats are
      associated with electrocorticogram desynchronization.
AB  - In awake rats a single recurrent larger tidal volume (deep breaths) occurs at
      regular intervals, followed by oscillations in arterial pressure and heart rate.
      In the present study we recorded the changes in blood pressure, heart rate and
      ventilation during the wakefulness-sleep cycle identified by
      electrocorticographic records in order to determine whether the deep breaths and
      cardiovascular oscillations were associated with changes in the
      electrocorticogram. During several episodes of slow-wave sleep (SWS) in 7 rats
      the deep breaths and oscillations in arterial pressure and heart rate were
      preceded by SWS desynchronization. The interval between deep breaths during SWS
      was 71 +/- 4 s, the period between initial desynchronization and the generation
      of deep breaths was 3.98 +/- 0.45 s and the duration of SWS desynchronization was
      11 +/- 0.65 s. Hypotension (-16 +/- 1 mmHg) and tachycardia (+15 +/- 5 bpm) were
      observed during deep breaths in the SWS state. These data indicate that the
      oscillations in arterial pressure and heart rate during SWS are associated with
      deep breaths, which in turn are preceded by desynchronization of the
      electrocorticogram in this state of sleep.

PMID- 9532250
TI  - Inflammation markers and symptom activity in children with bronchial asthma.
      Influence of atopy and eczema.
AB  - BACKGROUND: Eosinophil cationic protein (ECP) has been reported to reflect the
      eosinophil inflammatory activity in asthma. However, the relative impact of
      asthma symptoms and atopic eczema upon serum (s)-ECP in asthmatic children has
      not been established. OBJECTIVES: To examine s-ECP levels and s-myeloperoxidase
      (MPO) in relation to asthma symptoms and atopic eczema in asthmatic children.
      METHODS: S-ECP and s-MPO were assessed in relation to symptom activity, lung
      function, exercise-induced bronchoconstriction and bronchial responsiveness in
      101 children; median age 9 years, range 1-16 years; with moderate to severe
      asthma, admitted to Voksentoppen Center. RESULTS: S-ECP was significantly higher
      in children with persistent compared to episodic or no asthma symptoms in the
      past four weeks. S-ECP was also higher in children with atopic compared to non
      atopic asthma, as well as in those with active compared to past history or no
      history of atopic eczema. S-MPO was higher in children with persistent asthma
      symptoms, but did not differ in relation to atopy or eczema state. Persistent
      asthma symptoms had the greatest impact upon s-ECP levels, followed by atopy and
      active eczema. CONCLUSION: S-ECP may be used in assessing symptom activity in
      asthmatic children, but with the realisation that active eczema and the presence
      of atopy may also influence levels.

PMID- 9532251
TI  - Endotoxin exposure and symptoms in asthmatic children.
AB  - Endotoxins (ET) are pro-inflammatory substances present in house dust which may
      increase non-specific bronchial reactivity in asthmatic patients. Endotoxins
      (EU/g) and Der p 1 levels were compared in the homes of ten asthmatic and ten
      control children, aged 6-16 years, living in Sao Paulo, Brazil. The houses were
      visited once a month from February 1993 to February 1994 and dust samples were
      collected from the bedding and floor of each subject's house. No significant
      differences were observed in ET and Der p 1 levels in the homes of asthmatics and
      controls. The highest ET levels were detected in January and November, whereas
      the lowest levels were detected in April and August (p < 0.05), demonstrating a
      distinct seasonal distribution. The highest Der p 1 levels in bedding were
      observed in July and the lowest in February (p < 0.05), while Der p 1 levels in
      floor did not show significant differences throughout the year. Symptom and
      medication scores were evaluated monthly in the group of asthmatic children.
      There was a significant correlation (p < 0.05, r = 0.63) between clinical symptom
      scores and ET exposure, however no significant correlation was found for mite
      exposure (p > 0.05, r = 0.19). The results suggest that ET exposure exacerbates
      asthmatic symptoms in mite allergic, asthmatic children.

PMID- 9532252
TI  - Variable increases of IgG and IgM antibodies in milk of IgA deficient women.
AB  - Serum, milk and saliva from seven IgA deficient mothers were studied for the
      presence of IgA, IgG and IgM antibodies to Escherichia coli and poliovirus
      antigens. Different variable patterns were obtained. One mother had very much
      increased IgM and IgG antibodies in milk and saliva against both antigens; the
      milk IgG antibodies were 11-14 times higher than the reference milk pool. Another
      mother showed also striking increases of both IgM and IgG antibodies in milk, as
      well as in saliva where the increases were much higher for the poliovirus than
      the E. coli antibodies. Yet another mother showed a certain increase of IgM but
      not of IgG antibodies in the milk. The uneven appearance of IgG and IgM
      antibodies in serum and secretions suggests local production. So do the
      differences of antibody avidities, the variations in IgG subclass distribution of
      antibodies and different patterns after isoelectric focusing (IEF)/immunoblotting
      analysis of antibody spectrotypes in secretions and serum. The study illustrates
      the variable patterns of compensatory increases of IgG and IgM antibodies which
      may occur in IgA deficiency. It also shows that the milk from IgA deficient
      mothers can still be rich in antibodies, in spite of the lack of secretory IgA.

PMID- 9532253
TI  - Parity among atopic and non-atopic mothers.
AB  - A temporary Th2 skewed immunity is essential for a successful outcome of
      pregnancy. It is also a hallmark of atopic disease. We recorded the number of
      siblings to 3667 children in relation to maternal atopy. In all, 65% of the
      allergic and 56% of the non-allergic mothers had more than one child (p < 0.001).
      These data support a hypothesis that the atopic genotype may be associated with
      an increased likelihood for a successful outcome of pregnancy and thus from an
      evolutionary point of view compensate for the less efficient host defence against
      microbial infections associated with this type of immunity.

PMID- 9532254
TI  - The "nasal pool"-device for challenge and lavage of the nasal mucosa in children:
      histamine-induced plasma exudation responses.
AB  - The accessibility of the nasal airway allows important examination of the airway
      mucosa in health and disease. However, the current methods for nasal challenge
      and lavage in children suffer from several shortcomings. In the present study, we
      have assessed the utility of a recently developed "nasal pool"-device in 7-9 year
      old children, and explored the ability of the nasal mucosa of these school
      children to mount a plasma exudation response (lumenal entry of bulk plasma).
      Isotonic saline was instilled and maintained (1 min) as a "pool" in the
      unilateral nasal cavity. Recovery of the "pool" (lavage fluids) was determined.
      Concomitant challenge and lavage was then performed by exposing the nasal mucosa
      to a "pool" of isotonic saline and histamine (40-400 micrograms/ml) for 2 min.
      "Pool" fluids were analysed for alpha 2-macroglobulin as an index of
      microvascular-epithelial exudation of bulk plasma. The school-children
      successfully managed to carry out nasal lavages as well as concomitant histamine
      challenges and lavages with the "nasal pool"-device. The recovery of the nasal
      lavage fluids was almost quantitative (> 85%) and thus well reproducible.
      Histamine produced significant exudation of bulk plasma (alpha 2-macroglobulin).
      We suggest that the "nasal pool"-device is well suited for challenge and lavage
      of the nasal airway mucosa in children above 6 years of age, and conclude that
      lumenal entry of multipotent humoural protein-systems may be an important first
      line respiratory defence mechanism in children.

PMID- 9532256
TI  - HLA antigens in asthmatic children.
AB  - The purpose of the present study was to analyze the frequency of HLA-DR and DQ
      antigens in Brazilian asthmatic children with skin-test and RAST positivity to
      Dermatophagoides pteronyssinus. The comparison of HLA-DR and DQ antigenic
      frequencies between patients (n = 30) and controls disclosed a significantly
      higher HLA-DQ2 frequency in the patients (60% versus 34%, p = 0.013; R. R. =
      2.8).

PMID- 9532255
TI  - Cytokines in nasal fluids from school children with seasonal allergic rhinitis.
AB  - Allergic rhinitis is a particularly good model for studies of cytokine production
      in vivo. In this study the occurrence of the cytokines IL-4, IL-5, IL-10 and IFN
      gamma as well as the soluble receptor for IL-4 in nasal lavage fluids were
      assayed in 38 school children, with seasonal allergic rhinitis, and 19 healthy
      age-matched, non-atopic controls, using highly sensitive enzyme immunoassays. IL
      4 levels in patients with seasonal allergic rhinitis were markedly increased in
      comparison with those in non-atopic controls or in atopic patients before the
      start of the pollen season. In controls, but not in the atopic patients, levels
      of IFN-gamma and IL-5 were significantly higher in specimens obtained during the
      pollen season than in those obtained outside the season. The IL-4/IFN-gamma
      ratios were significantly higher in atopic than in non-atopic subjects and
      further increased in atopic patients during the season. In addition to IL-4,
      elevated levels of IL-10 were observed in association with seasonal rhinitis.
      Following treatment with a topical steroid (budesonide) there was a statistically
      significant increase of the levels of soluble IL-4 receptor. These findings
      indicate that nonatopic and atopic individuals react to pollen exposure with
      distinct cytokine patterns in agreement with the Th1/Th2 concept. Topical
      steroids may possibly decrease inflammation by increasing the formation of
      soluble IL-4 receptor.

PMID- 9532257
TI  - A case of cow's milk allergy in the neonatal period--evidence for intrauterine
      sensitization?
AB  - Clinical manifestations of cow's milk allergy rarely occur in the first days
      after birth. We report on a newborn presenting with hemorrhagic meconium in the
      first hour of life followed by bloody diarrhea in the next few days. At day 14,
      an elevated total IgE, specific IgE to cow's milk and an eosinophilia in
      peripheral blood were found. Symptoms disappeared when the milk feed was changed
      to an extensively hydrolyzed casein-formula. Two challenges with cow's milk
      formula (on day 30 and at 7 months of age) were followed by recurrence of
      vomiting, watery diarrhea and failure to thrive. At the age of 17 months cow's
      milk was tolerated well. Although other pathogenetic mechanisms cannot completely
      be ruled out, there is strong evidence that cow's milk allergy--induced by intra
      uterine sensitization--explains the symptoms in our patient. In conclusion, cow's
      milk allergy can occur even in the first days of life, and our clinical
      observation supports the concept of intra-uterine sensitization to allergens.

PMID- 9532259
TI  - Anaerobic susceptibility testing: where are we and where do we go from here?

PMID- 9532258
TI  - Hypersensitivity to the diphtheria component in the Di-Te-Pol vaccine. A type I
      allergic reaction demonstrated by basophil histamine release.
AB  - We describe a two year-old multiallergic boy who developed generalized urticaria
      after the third Di-Te-Pol vaccination. A Type I reaction to the vaccine was
      demonstrated by performing basophil histamine release to the complete vaccine.
      Further, we found that the reaction could be exclusively ascribed to Diphtheria
      Toxoid whereas no release was observed by the Polio and Tetanus component. The
      latter result was confirmed since no specific IgE to Tetanus Toxoid could be
      demonstrated.

PMID- 9532260
TI  - Quantitation of bacterial adhesion to polymer surfaces by bioluminescence.
AB  - Quantitation of microbes adhering to a surface is commonly used in studies of
      microbial adhesion to different surfaces. We have quantified different
      staphylococcal strains adhering to polymer surfaces by measuring bacterial ATP
      (adenosine triphosphate) by bioluminescence. The method is sensitive, having a
      detection limit of 10(4) bacterial cells. Viable counting of bacterial cells may
      yield falsely low results due to the presence of "dormant" and adherent bacteria.
      By using bioluminescence, this can be avoided. Cells of different bacterial
      species and cells of strains of the same species were shown to differ
      significantly in their basal ATP content (8.7 x 10(-13) - 5.2 x 10(-22) MATP).
      The size of adherent and planktonic bacteria decreased with time (0.7 micron-
      >0.3 micron, 20 days). During incubation in nutrient-poor buffer ("starvation"),
      the ATP content of adherent bacteria decreased after 24-96 h whereas that of
      planktonic bacteria was stable over 20 days. The presence of human serum or
      plasma did not interfere significantly with the test results. Since the ATP
      concentration of bacterial strains of different species varies and is also
      influenced by the growth conditions of bacteria (solid or liquid culture medium),
      a species-specific standard curve has to be established for bacteria grown under
      the same culture conditions. We conclude that the method is a sensitive tool to
      quantify adherent bacteria during experiments lasting for less than 6 h and
      constitutes a valuable method to be used in conjunction with different
      microscopical techniques.

PMID- 9532261
TI  - In vitro anti-staphylococcal activity of heparinized biomaterials bonded with
      combinations of rifampicin.
AB  - Biomaterial implants in various human body tissues are highly susceptible to
      bacterial colonization. We report here on the coating of heparinized biomaterials
      with heparin binding extracellular matrix proteins giving special regard to the
      efficient adsorption and slow release of antibiotics. Heparin was partially
      degraded and the resulting fragments were covalently end-point attached to 0.5 cm
      long silicone biomaterial surface. Collagen type I was immobilized on the
      heparinized biomaterials and then cross-linked with acyl-azide or carbodiimide.
      Finally, the resulting biosurfaces were exposed to antibiotics, i.e. rifampicin
      in combination with cefuroxime, fusidic acid, ofloxacin or vancomycin,
      respectively. The antibiotic bonded biomaterials were evaluated for their anti
      staphylococcal activity after elution in NaCl, serum or blood by measuring the
      zones of inhibition for S. epidermidis strain RP12. Furthermore, we examined the
      in-vitro colonization resistance to S. epidermidis RP12 for these combinations of
      rifampicin-bonded biomaterials by an ATP bioluminescence assay. The ATP
      measurements showed that initially adherent bacteria were eradicated from the
      polymer surface, for at least 24 or 48 h (fusidic acid > cefuroxime > vancomycin
      > ofloxacin). The anti-staphylococcal activity of rifampicin-fusidic acid bonded
      heparinized biomaterials seems of sufficient duration and efficacy to merit
      testing in an animal model.

PMID- 9532262
TI  - In-vitro susceptibility of group A beta-haemolytic streptococci (GABHS) to
      penicillin, erythromycin, clarithromycin and azithromycin in Styria, Austria.
AB  - 248 Strains of group A beta-haemolytic streptococci (GABHS) were tested against
      penicillin and the macrolide antibiotics, erythromycin, clarithromycin and
      azithromycin. 213 (85.9%) GABHS isolates were taken from throat swabs from
      patients with pharyngotonsillitis, 35 isolates (14.1%) were from other body sites
      or from invasive infections. The age of the patients ranged from 9 months to 89
      years, 155 of the patients (62.5%) were below 10 years of age. The results of the
      E-test method and a disk diffusion assay were compared; to classify the phenotype
      of the erythromycin-resistant strains, a disk induction test was carried out.
      None of the 248 GABHS strains showed resistance to penicillin, whereas 53 GABHS
      isolates (21.4%) were resistant to the macrolide antibiotics included in the
      test. There were only minor discrepancies between the two testing methods. The
      MIC data obtained with the E-test method suggested that among the macrolides,
      erythromycin and clarithromycin had slightly higher antistreptococcal activity
      than azithromycin in vitro. 50 (94.3%) of the erythromycin-resistant GABHS showed
      the pattern of novel resistance (M phenotype), 2 (3.8%) strains showed inducible
      resistance (IR) and 1 (1.9%) strain exhibited consecutive resistance (CR).

PMID- 9532263
TI  - Risk of infection with Borrelia burgdorferi sensu lato for a host in relation to
      the duration of nymphal Ixodes ricinus feeding and the method of tick removal.
AB  - The objectives of the present study were to investigate the risk of B.
      burgdorferi s.1. (Bb)-transmission by I. ricinus-nymphs to a host (i) after
      different periods of feeding, and (ii) with regard to the particular method of
      tick removal. On each of 72 Mongolian gerbils 3 tick nymphs taken from a highly
      infected batch were allowed to feed in a small capsule. Feeding ticks were
      removed 16.7, 28.9, 47.0, and 65.2 hrs post-attachment. In each of these 4 groups
      3 sub-groups with 6 gerbils each were deticked by (a) pulling ticks out with
      forceps without any pretreatment, (b) pulling ticks out after 3 min of intensive
      squeezing, and (c) applying nail polish to ticks 1.1 hrs before removal. The
      infection status in each gerbil was subsequently determined by larval
      xenodiagnosis. All gerbils with ticks removed > or = 47 hrs post-attachment were
      found to be infected. After 16.7 hrs as well as after 28.9 hrs of tick feeding,
      approximately 50% of the gerbils had acquired a transmissible infection, thus Bb
      transmission to a host may even occur in the early phases of I. ricinus feeding.
      There is no evidence from this study that the tick removal method used has any
      significant influence on a host's Bb-infection risk.

PMID- 9532264
TI  - Detection of fungemia from blood cultures using the BACTEC 9240 instrument.
AB  - From January 1995 to November 1996, 14,623 resin-containing blood culture vials
      were tested with the BACTEC fluorescent series instrument. A total of 1560
      microorganisms were recovered. 48 of the microorganisms were fungi. We could
      demonstrate the ability of the BACTEC 9240 to detect cases of fungemia with
      Candida species and moulds such as Aspergillus fumigatus (4 cases) and Fusarium
      solani (1 case).

PMID- 9532265
TI  - Infant botulism during a one year period in San Luis, Argentina.
AB  - Five cases of infant botulism which occurred during the period from May 1995 to
      May 1996 in San Luis, Argentina, are reported. Infant botulism was confirmed in
      all patients by isolation of Clostridium botulinum type A from stool culture and
      by the toxin assay. Toxin was found in the serum of one of them. All patients
      required hospitalization with treatment consisting of supportive especially
      respiratory and nutritional care. At the time of discharge from the hospital,
      three patients had a good recovery, although two of them had mild difficulties in
      sucking or constipation. C. botulinum was not detected in samples of honey which
      had been given to two of the patients.

PMID- 9532266
TI  - Further characterization of Staphylococcus epidermidis transposon mutants
      deficient in primary attachment or intercellular adhesion.
AB  - Biofilm formation is suggested to be the result of primary attachment of
      Staphylococcus epidermidis cells to a polymer surface followed by accumulation in
      multilayered cell clusters. Here we describe the further characterization of
      transposon (Tn917) mutants of Staphylococcus epidermidis O-47 having been biofilm
      negative in a polystyrene microtiter plate adhesion assay. Among 5000 Tn917
      insertion strains, we isolated four biofilm-negative mutants, each carrying one
      copy of Tn917. The mutants could be divided into two phenotypic classes: class A
      (mut1 and mut1a) and class B (mut2 and mut2a). Mutants of phenotype class A
      lacked four cell surface proteins and were affected in the primary attachment to
      polystyrene, but remained able to form multilayered cell clusters and to produce
      PIA. Mutants of phenotype class B were able to attach to polystyrene, but did not
      form multilayered cell clusters nor produce PIA. The cell surface protein pattern
      relative to the wild type was unchanged in class B mutants. On Congo red agar,
      the wild type and class A mutants formed black colonies (positive reaction on
      Congo red agar) while class B mutant colonies were red (negative reaction). The
      initial binding of cells to polystyrene and the ability to form multilayered cell
      clusters were found to be phenotypically and genetically distinct traits.

PMID- 9532267
TI  - Generalized transduction for genetic linkage analysis and transfer of transposon
      insertions in different Staphylococcus epidermidis strains.
AB  - Staphylococcus epidermidis phage 48 was used to efficiently transduce plasmid
      pTV1ts and a chromosomal Tn917 insertion M27 from S. epidermidis 13-1 to biofilm
      producing clinical S. epidermidis isolates 1457, 9142, and 8400. The Tn917
      insertion leading to the biofilm-negative phenotype of transposon mutant M10 was
      sequentially transduced to biofilm-producing S. epidermidis 1457 using S.
      epidermidis phage 48 and then, using the resulting biofilm-negative transductant
      1457-M10 as a donor, into several unrelated biofilm-producing clinical S.
      epidermidis isolates using S. epidermidis phage 71. All resultant transductants
      displayed a completely biofilm-negative phenotype. In addition, S. epidermidis
      phage 71 was adapted to S. epidermidis 1457 and 8400, which allowed generalized
      transduction of transposon insertions in these wild-type strains. As Tn917
      predominantly transposed into endogenous plasmids of all three strains used, an
      efficient system for chromosomal transposon mutagenesis was established by curing
      of S. epidermidis 1457 of a single endogenous plasmid p1457 by sodium
      dodecylsulfate treatment. After transduction of the resulting derivative, S.
      epidermidis 1457c with pTV1ts, insertion of transposon Tn917 to different sites
      of the chromosome of S. epidermidis 1457c was observed. Biofilm-producing S.
      epidermidis 1457c x pTV1ts was used to isolate a biofilm-negative transposon
      mutant (1457c-M3) with a chromosomal insertion apparently different from two
      previously isolated isogenic biofilm-negative transposon mutants, M10 and M11
      (Mack, D., M. Nedelmann, A. Krokotsch, A. Schwarzkopf, J. Heesemann, and R.
      Laufs: Infect Immun 62 [1994] 3244-3253). S. epidermidis phage 71 was used to
      prove genetic linkage between transposon insertion and altered phenotype by
      generalized transduction. In combination with phage transduction, 1457c x pTV1ts
      will be a useful tool facilitating the study of bacterial determinants of the
      pathogenicity of S. epidermidis.

PMID- 9532268
TI  - Prevalence of primary bloodstream infections in representative German hospitals
      and their association with central and peripheral vascular catheters.
AB  - The prevalence of noncentral and central lines and the prevalence of nosocomial
      primary bloodstream infections was investigated in 72 representative German
      hospitals (NIDEP Study). Data from a total of 14,966 patients were documented. On
      the prevalence day, it amounted to 23.9% for noncentral and 5.1% for central
      lines. The total prevalence of nosocomial primary bloodstream infections was
      0.3%, 8.3% of all nosocomial infections recorded were primary bloodstream
      infections. The device utilization rate of vascular catheters was retrospectively
      observed for both the prevalence day and another 6 days. The device utilization
      rate was 27.3% for peripheral and 6.1% for central catheters with higher rates in
      west Germany. The associated incidence density of primary nosocomial bloodstream
      infections per 1000 catheter-days was 0.3 for noncentral and 0.8 for central
      lines. In 61.4%, the primary bloodstream infections were microbiologically
      confirmed. In 52.6% of cases, Gram-positive bacteria were isolated
      (Staphylococcus aureus: 15.8%, other coagulase negative Staphylococcus species:
      34.2%) and in 47.4%, Gram-negative ones (mostly: Escherichia coli: 13.2% and
      Klebsiella species: 10.5%). Prevention to reduce nosocomial bloodstream
      infections is possible by antimicrobial establishing specially trained infusion
      therapy teams, using antimicrobial or antiseptic impregnated bloodstream
      catheters and a strict review of the indication for a vascular catheter together
      with a minimization of catheter days.

PMID- 9532269
TI  - A database system for fragment patterns of genomic DNA of Staphylococcus aureus.
AB  - The increasing use of molecular fingerprints in the epidemiology of bacterial
      nosocomial infections urgently demands a computerised analysis and storage of
      corresponding patterns, especially with regard to results obtained at different
      times and in different laboratories. This paper presents a database system in
      connection with cluster analysis of clonal relations by using genomic DNA
      fragment patterns of S. aureus (SmaI-digestion, pulsed-field gel electrophoresis)
      as an example: The database is operated under MS-Access, version 2.0. The cluster
      analysis is based on an optimising similarity algorithm.

PMID- 9532270
TI  - Acridine-orange leucocyte cytospin (AOLC) test as an in-situ method for the
      diagnosis of central venous catheter (CVC)-related sepsis in adult risk patients.
AB  - The AOLC method for the in-situ diagnosis of catheter-associated septicemia was
      evaluated in adult intensive care patients. 55 blood samples and corresponding
      CVC tips were examined using the AOLC method, the semiquantitative roll plate
      method and the broth immersion method. In 4 patients (7.3%), a CVC-related
      septicemia was diagnosed, 10 patients (18.2%) showed a colonisation of their
      central venous access. The AOLC method was positive in 50% of the cases with CVC
      related septicemia and in 20% of the colonized patients. Thus, we do not
      recommend the AOLC test as a routine method for the diagnosis of suspected CVC
      related infection but as a facultative additional diagnostic measure for certain
      risk patients.

PMID- 9532271
TI  - Increased risk of catheter colonization and catheter-related infections in severe
      immunocompromized patients with multiple myeloma undergoing high-dose
      glucocorticoid treatment.
AB  - Catheter-related infections (CRI) are an important problem in medicine because of
      major consequences for treatment, prolongation of hospitalization and increasing
      therapy costs. Malignancies, immunodeficiency, severe burns and malnutrition
      compromise host defense. Studies to quantify the increased risk of CRI in
      immunocompromised patients are required. We analyzed the influence of
      immunoglobulin deficiency and high-dose glucocorticoid treatment in patients with
      multiple myeloma with regard to catheter colonization and CRI. In patients with
      multiple myeloma, central venous catheters (CVC) were significantly more
      frequently colonized (> 15 CFU) as compared to patients with other malignancies
      undergoing chemotherapy. We found a tendency towards a higher CRI rate in the
      myeloma patient group. Interestingly, despite of the significantly higher
      incidence of catheter colonization and a tendency towards higher CRI rates in
      severely immunocompromised patients, the incidence of signs of local (redness of
      the entry site) and systemic (fever) host reactions is reduced in myeloma
      patients. To decrease the CRI rate in myeloma patients during chemotherapy which
      includes high-dose glucocorticoids, we use antibacterial (silver-coated)
      catheters.

PMID- 9532272
TI  - Effect of surface modifications of intraocular lenses on the adherence of
      Staphylococcus epidermidis.
AB  - The development of polymers with different surface properties and surface
      modifications of intraocular lenses (IOL) should reduce foreign body reactions
      after implantation by reducing the surface hydrophobicity of the lenses. It was
      examined how far such surface variations influenced the adhesiveness of bacteria.
      The most common organism isolated from cases of postoperative endophthalmitis is
      Staphylococcus epidermidis. For this reason, three strains of this species, the
      type strain ATCC 14990 and two clinical isolates (8687, 6579 I), with different
      hydrophobic surfaces, were studied. IOL made of PMMA, silicone, and a copolymer
      as well as PMMA lenses with modified surfaces (unpolished, polished, silanized,
      and heparinized) were used. Bacteria were radiolabelled with 3H-thymidine and the
      adherent bacteria were calculated per mm2 of lens surface. The three strains
      adhered better to the unpolished surface of silicone than to PMMA. Treatment of
      PMMA surface by polishing diminished the differences between the strains. An
      influence of hydrophobic interactions on the adherence of S. epidermidis ATCC
      14990 was demonstrated. The adherence of this hydrophobic type strain was clearly
      reduced by heparinization of the PMMA surface. In contrast, the hydrophilic
      catheter isolate 6579 I adhered better to modified surfaces. This strain differed
      clearly in its PFGE pattern from both hydrophobic strains. Hydrophobic
      interactions play a role in the bacterial adherence to intraocular lenses in
      vitro and in vivo. Modifications of polymer surfaces, however, can result in
      rather different effects depending on the bacterial surface composition and
      properties.

PMID- 9532273
TI  - A silicone ventricular catheter coated with a combination of rifampin and
      trimethoprim for the prevention of catheter-related infections.
AB  - So-called antiinfective catheters which are generated by incorporation of
      antimicrobial substances into polymers appear to be effectful devices in the
      prevention of catheter related infections. Such devices mainly act by prevention
      of bacterial colonization of the catheter surface rather than by inhibition of
      adherence. In a preceding study, we developed a rifampin-containing silicone
      catheter for the prevention of ventricular shunt infection. In the present study,
      this work was continued with a combination of antimicrobials incorporated in
      silicone ventricular catheters to reduce the risk of rifampin resistance and to
      expand the antimicrobial spectrum. We found that the drug release kinetics could
      be greatly influenced by the incorporation conditions. It was possible to
      incorporate an optimal antibiotic combination of rifampin and trimethoprim into
      the polymer resulting in defined release rates and a defined total release. A
      catheter loaded with this combination showed an excellent reduction of the
      colonization with Staphylococcus aureus (99.97% reduction within 3 hours) under
      in-vitro conditions.

PMID- 9532274
TI  - In vitro efficacy of a hydrophilic central venous catheter loaded with silver to
      prevent microbial colonization.
AB  - A method was developed to load the surface of a central venous catheter with
      silver to prevent bacterial colonization. Silver confers a broad antimicrobial
      activity with a relatively low risk of resistance. Catheters were incubated with
      a silver nitrate solution in different concentrations. The solvent, incubation
      temperature and incubation period were varied to examine the influence on the
      catheter loading. With increasing incubation temperature, time and concentration
      of silver nitrate, higher rates of silver elution were observed by atomic
      absorption spectroscopy. Furthermore, by using ethanol-water as a solvent instead
      of pure water, the amount of silver bound to the catheter surface was enhanced.
      The release of silver from the catheter surface is mainly controlled by first
      order kinetics. Antimicrobial efficacy of the modified catheter, in comparison to
      unloaded catheters, was tested in a stationary and a dynamic model with different
      microorganisms. Adherence experiments with Candida albicans showed almost
      complete inhibition of growth during a period of 72 hours, including initial
      adherence. While initial adherence of bacteria could not be prevented, these
      experiments showed an excellent reduction of bacterial colonization. In a
      perfusion model, adhesion of E. coli could be reduced for at least seven days.
      Further studies are planned to examine prolonged antimicrobial effects.

PMID- 9532275
TI  - Diaschisis and neurobehavior.
AB  - We review forms of diaschisis and their relationship with neurobehavioral and
      neuropsychological findings. The following forms of diaschisis are discussed: (1)
      cortico-cerebellar diaschisis; (2) cerebello-cortical diaschisis; (3)
      transhemispheric diaschisis; (4) cortico-thalamic diaschisis; (5) thalamo
      cortical diaschisis; and (6) basal ganglia-cortical diaschisis. For each form,
      the neurobehavioral and neuropsychological findings are discussed. Diaschisis can
      be classified from the behavioral point of view as follows: (1) forms in which
      the metabolic effect at distance is not followed by neurobehavioral impairment;
      (2) forms in which the remote metabolic impairment could induce neurobehavioral
      and neuropsychological disorders; and (3) forms in which the role of the lesion
      itself and its remote metabolic effects on the production of neurobehavioral and
      neuropsychological abnormalities cannot be disentangled.

PMID- 9532276
TI  - Magnetic resonance spectroscopy guided brain tumor resection: differentiation
      between recurrent glioma and radiation change in two diagnostically difficult
      cases.
AB  - BACKGROUND: It is often difficult to differentiate a recurrent glioma from the
      effects of post-operative radiotherapy by means of conventional neurodiagnostic
      imaging. Proton magnetic resonance spectroscopic imaging (1H-MRSI), that allows
      in vivo measurements of the concentration of brain metabolites such as choline
      containing phospholipids (Cho), may provide in vivo biochemical information
      helpful in distinguishing areas of tumor recurrence from areas of radiation
      effect. PATIENTS AND METHODS: Two patients who had undergone resection and post
      operative radiotherapy for a cerebral glioma became newly symptomatic. Computed
      tomographic (CT) and magnetic resonance imaging (MRI) performed after the
      intravenous infusion of contrast material, and in one case,
      [18F]fluorodeoxyglucose positron emission tomography (PET), could not
      differentiate between the possibilities of recurrent glioma and radiation effect.
      The patients underwent 1H-MRSI prior to reoperation and the 1H-MRSI results were
      compared to histological findings originating from the same locations. RESULTS: A
      high Cho signal measured by 1H-MRSI was seen in areas of histologically-proven
      dense tumor recurrence, while low Cho signal was present where radiation changes
      predominated. CONCLUSIONS: The differentiation between the recurrence of a
      cerebral glioma and the effects of post-operative irradiation was achieved using
      1H-MRSI in these two patients whose conventional neurodiagnostic imaging was
      equivocal for such a distinction. Where these two conditions are present,
      metabolite images from 1H-MRSI, such as that based on Cho, can be co-registered
      with other imaging modalities such as MRI and may also be integrated with
      functional MRI or functional PET within a multimodal imaging-guided surgical
      navigation system to assure maximal resection of recurrent tumor while minimizing
      the risk of added neurological damage.

PMID- 9532277
TI  - Burden of illness of multiple sclerosis: Part I: Cost of illness. The Canadian
      Burden of Illness Study Group.
AB  - BACKGROUND: Multiple sclerosis (MS) is a common neurologic disease in young and
      middle-aged adults affecting approximately 35,000 Canadians. The objectives of
      this study were to estimate the annual and lifetime costs of MS from the Canadian
      societal perspective. METHODS: Patients were consecutively recruited by
      neurologists in 14 MS outpatient clinics across Canada. They were classified
      according to the Expanded Disability Status Scale (EDSS) into three groups: mild
      (EDSS < or = 2.5), moderate (EDSS = 3.0-6.0) and severe (EDSS > or = 6.5).
      Sociodemographic, clinical and resource utilization data were collected
      retrospectively for the three months prior to patient inclusion. Costing of
      resources was performed from Ministry of Health, private third party payers,
      patient and societal perspectives. Average Canadian costs ($CDN 1995) were valued
      from available provincial data. RESULTS: A total of 198 patients were included in
      the analysis (mild: n = 62, moderate: n = 68 and severe: n = 68). Costs increased
      with increasing EDSS scores, from all perspectives. The annualized societal costs
      per patient were $CDN14,523, $CDN21,698 and $CDN37,024 for the mild, moderate and
      severe groups, respectively. In all severity groups, most of the financial burden
      is borne by patients, from 74% to 88%. Indirect costs, namely lost daily
      activity/leisure time and lost productivity, were the major societal cost
      drivers. The lifetime cost of MS, including patient institutionalization, was
      estimated to be $CDN1,608,000 per patient. CONCLUSIONS: In Canada, MS is
      associated with enormous direct and indirect costs. Patients carry most of the
      economic burden of this disease. The results of this burden of illness study
      provide a basis for cost-effectiveness analyses of new therapeutic interventions
      for MS.

PMID- 9532278
TI  - Burden of illness of multiple sclerosis: Part II: Quality of life. The Canadian
      Burden of Illness Study Group.
AB  - OBJECTIVE: To measure the quality of life (QoL) of multiple sclerosis (MS)
      patients in Canada using a generic QoL instrument, the SF-36. METHODS: QoL was
      assessed in 198 MS patients, recruited from 14 MS Clinics in Canada, and
      stratified into three levels of disease severity, based on their Expanded
      Disability Status Scale (EDSS) score. Statistical tests were used to compare QoL
      scores between severity groups and to identify possible relationships between QoL
      and patient sociodemographic, clinical and economic parameters. RESULTS: QoL
      scores for all eight scales of the SF-36 were substantially reduced early in the
      disease. Compared to the normal population, QoL scores for patients with mild MS
      were on average 30% lower for all SF-36 scales. With EDSS progression a
      statistically significant decrease in three of the SF-36 domains (physical
      function, role-physical, and social function) was observed. There were no
      significant correlations between patient parameters considered and QoL scores.
      CONCLUSIONS: QoL of MS patients collapses early in the disease. With EDSS
      progression, physical functioning scales show further decreases in QoL. The
      absence of further changes in the mental SF-36 scales may be a reflection of
      patient adaptation to the disease and/or effective support care. However, the SF
      36 instrument may be insensitive to some of the QoL changes in MS and a disease
      specific instrument may provide additional information on QoL, particularly at
      later stages of the disease. This study provides a basis for future research
      aimed at improving management of MS.

PMID- 9532279
TI  - Evaluation of selection criteria used in Alzheimer's disease clinical trials.
AB  - BACKGROUND: In the absence of a biological marker for Alzheimer's disease (AD),
      diagnosis has to be achieved using clinical criteria sets such as those outlined
      in DSM-IV, NINCDS-ADRDA, or ICD-10. As these criteria are quite broadly defined,
      there may be inter-rater variability in interpretation. METHODS: Using a
      previously published CT scan measuring technique which correlates well with
      diagnoses achieved using the NINCDS-ADRDA criteria as interpreted at our clinic,
      we chose to independently examine and reach a diagnosis in patients selected for
      participation in clinical trials of therapeutic agents for the treatment of AD.
      Forty-four CT scans from six investigators across Canada were examined using this
      model. All patients had been diagnosed as having AD by NINCDS-ADRDA criteria and
      were deemed acceptable to participate in a clinical trial. RESULTS: The
      diagnostic concordance achieved in the original published model was 91.5%. The
      diagnostic concordance in the population currently being studied was 77.3%.
      However when examined by site, results ranged from 57.1% to 100%. Using the
      model, an index of atrophy and a probability of diagnosis of AD can be
      determined. Across sites, there were statistically significant differences in
      these measures (p < or = 0.035). The mean probability of diagnosis of AD across
      sites ranged from 0.56 to 0.94. Although the sites with lower probabilities had
      slightly lower mean ages and slightly less atrophy, there was no overall
      correlation of the atrophy measures with age. CONCLUSIONS: Current results raise
      the possibility that the selection of patients for AD clinical trials using
      current diagnostic criteria sets may not be adequate and conclusions with respect
      to agent efficacy could be flawed.

PMID- 9532281
TI  - Motor pathway analysis in HAM/TSP using magnetic stimulation and F-waves.
AB  - BACKGROUND: Tropical Spastic Paraparesis/HTLV-I Associated Myelopathy (HAM/TSP)
      is a chronic, progressive myelopathy endemic to the Caribbean. In HAM/TSP,
      peripheral motor pathways have been assessed using electromyography and nerve
      conduction studies; central motor pathways have been assessed to a limited extent
      using electrocortical stimulation. We used magnetic cortical stimulation (a
      painless alternative to electrocortical stimulation) and F-wave analysis to study
      conduction in the central and peripheral motor pathways in 18 HTLV-I
      seropositive, Jamaican TSP patients (ages 29-70 years; duration of symptoms 3-20
      years) and 22 normal controls. METHODS: Magnetic cortical stimulation was
      effected using a 9 cm diameter undamped MES10 coil. F-waves and M-responses were
      elicited by electrical stimulation of the ulnar nerve at the wrist, and deep
      peroneal stimulation at the knee. Stimulation and recording of response latencies
      in abductor digitii minimi (ADM) and tibialis anterior (TA) were carried out
      using a Cadwell Excel system. RESULTS: With cortical stimulation, response
      latencies (TMCTs) to ADM and TA were prolonged in the patients relative to
      controls. F-wave and M-response latencies were unaffected, suggesting no
      peripheral pathology. Latency (CMCT) between cortex and lumbar cord was
      significantly prolonged; that between cortex and C7/T1, also, but less markedly
      (P < 0.0005). Amplitudes of cortically evoked responses were significantly
      reduced only in the lower limbs (TA). CMCT increased as the disease progressed
      from mild to moderate, thereafter remaining largely unchanged. CONCLUSIONS: Meta
      analysis of interlaboratory control data revealed no significant differences in
      TMCTs between our controls and others studied using similar techniques. The
      observations are consistent with pathology affecting mainly the thoracolumbar
      cord in HAM/TSP.

PMID- 9532280
TI  - Increased basal ganglia iron in striatonigral degeneration: in vivo estimation
      with magnetic resonance.
AB  - BACKGROUND: As many as 20% of individuals with the clinical diagnosis of
      Parkinson's disease (PD) do not have the characteristic neuropathologic features
      of PD at post mortem. The striatonigral degeneration (SND) subtype of multiple
      system atrophy is one of the categories of pathology which may be incorrectly
      diagnosed as PD on the basis of clinical presentation. SND may be associated with
      increased iron deposition in the putamen which can be detected with magnetic
      resonance imaging. METHODS: We have estimated regional brain iron content in a
      patient with probable SND, using a novel imaging method developed in our
      laboratory, and have compared the results in this patient to those which we have
      previously reported in patients with PD and in age-matched controls. RESULTS: We
      observed that putamenal iron content was increased in our SND patient, beyond the
      95% confidence limit for inclusion in the PD group, even when considering
      clinical severity. In contrast, pallidal and thalamic iron were within the PD
      range. CONCLUSIONS: The demonstration of increased putamenal iron content may be
      a useful adjunctive investigative procedure in patients with suspected SND.

PMID- 9532282
TI  - Adenosine and migraine.
AB  - BACKGROUND: Adenosine is a powerful natural vasodilator that participates in the
      control of cerebral and meningeal blood flow. In this context, it could be
      involved in the pathophysiology of migraine, since it was previously reported
      that intravenous adenosine can precipitate crises in migraine patients. METHODS:
      We have investigated circulating adenosine levels in 12 patients suffering from
      migraine without aura, during crises and in crisis-free periods, and have
      compared the levels noted to those of a population of 10 controls. To determine
      if there are interactions between adenosine and serotonin, we examined the effect
      of adenosine and antagonists on the uptake and the release of (14C) serotonin by
      platelets. RESULTS AND CONCLUSION: We have reached a dual conclusion: 1) during
      migraine headaches there is an increase (mean 68%) in circulating adenosine
      levels and this increase may participate in cephalalgia; 2) activation of A2
      receptors by adenosine causes a dose-dependent serotonin uptake by platelets.
      This inhibition of uptake could participate in the rapid elimination of serotonin
      in migraine sufferers. As a result of this, the use of adenosine antagonists
      could be an effective complementary treatment for migraine.

PMID- 9532283
TI  - Correlation of peripheral nerve fiber loss and trinucleotide repeats in Machado
      Joseph disease.
AB  - BACKGROUND: Machado-Joseph disease (MJD) is a dominantly inherited cerebellar
      ataxia associated with spasticity, ophthalmoplegia and dystonia. There has been
      no report of electrophysiological or histological alterations of the peripheral
      nervous system in patients with MJD. METHODS: Four patients with MJD were
      identified by polymerase chain reaction. The peripheral nerves of these patients
      were subjected to electrophysiological testing and histological study.
      Correlation analyses were made between various clinical parameters and the
      electrophysiological and histological changes. RESULTS: Electrophysiological
      studies demonstrated a marked reduction of sensory action potential, acute
      denervation changes on needle EMG, as well as mild decrease in the compound motor
      action potential. Light microscopy of the sural nerves revealed clear loss of
      myelinated fibers, and morphometry studies showed a loss of large myelinated
      fibers. Moreover, the severity of these pathological changes was found to be
      related to the CAG repeat length in the MJD gene. CONCLUSION: Our findings
      indicated that the peripheral nervous system was frequently affected in patients
      with MJD. These findings were similar to those seen in Friedreich's ataxia,
      suggesting a loss of sensory and motor fibers probably following a lesion of the
      dorsal root ganglion and the anterior horns in the spinal cord. Furthermore, the
      number of CAG repeats seems to have an inverse relationship to the extent of
      pathological changes of the peripheral nerves.

PMID- 9532284
TI  - The frequency of phospholipid antibodies in an unselected stroke population.
AB  - BACKGROUND: Antibodies to cardiolipin and other phospholipids have been
      associated with recurrent thrombotic events, including stroke. METHODS: Over a 16
      month period we assessed an unselected cohort of 151 ischemic stroke patients for
      the presence of antiphospholipid antibodies. Patients with known systemic lupus
      erythematosis, systemic sclerosis, or Sjogrens Syndrome were excluded. Sera from
      patients admitted to hospital with a diagnosis of ischemic stroke (n = 151) and
      from controls (n = 111) assessed during the same period were tested for
      antiphospholipid antibodies (APLA) using 3 assays; anticardiolipin antibodies
      (ACA) by ELISA, prolonged activated partial thromboplastin time (APTT), and VDRL.
      RESULTS: The average age of ischemic stroke cases was 68 years (range 29 to 91)
      and of controls 63 years (range 29 to 86). The prevalence of APLA detected by at
      least one of the three methods was 12% for IS cases and 10% for controls. After
      correcting for known risk factors such as age, gender, diabetes mellitus, heart
      disease, hypertension, and smoking, the odds ratio for risk of stroke fell to 0.8
      (C.I. 0.4 to 1.2). CONCLUSIONS: Our findings suggest that APLA may not be an
      independent risk factor for ischemic stroke in unselected persons who do not have
      known systemic lupus erythematosis or systemic sclerosis but further evaluation
      of the role of lupus anticoagulant is indicated.

PMID- 9532285
TI  - Blood flow differences between leuko-araiosis with and without lacunar
      infarction.
AB  - BACKGROUND: The present study was designed to find the differences in regional
      cerebral blood flow and cerebrovascular acetazolamide reactivity between leuko
      araiosis with and without lacunar infarction. METHODS: Fifteen cases of leuko
      araiosis with lacunar infarction, 15 cases of leuko-araiosis without lacunar
      infarction and 15 age-matched controls in which leuko-araiosis and
      cerebrovascular diseases are absent (control group) were studied. The regional
      cerebral blood flow was measured using the stable xenon computed tomography
      method before and 20 minutes after intravenous injection of 17 mg/kg
      acetazolamide. RESULTS: The blood flows in the leuko-araiosis area and the
      lacunar area were significantly lower than the blood flow in the cerebral white
      matter. The blood flows in the cerebral cortex and the cerebral white matter were
      significantly lower in the leuko-araiosis with lacunar infarction group than in
      the leuko-araiosis without lacunar infarction group and the control group. The
      cerebrovascular acetazolamide reactivity in the leuko-araiosis area and the
      lacunar area was significantly lower than that in the cerebral white matter. The
      cerebrovascular acetazolamide reactivity in the cerebral cortex and the cerebral
      white matter was significantly lower in the leuko-araiosis with lacunar
      infarction group than in the leuko-araiosis without lacunar infarction group and
      the control group. CONCLUSIONS: The degree of arteriolosclerosis is considered to
      be more severe and the rate of association of hypertension was higher in leuko
      araiosis with lacunar infarction than in leuko-araiosis without lacunar
      infarction.

PMID- 9532286
TI  - Vasculitic basilar artery thrombosis in chronic Candida albicans meningitis.
AB  - BACKGROUND: Cerebrovascular complications of meningitis have been most
      extensively documented in the setting of acute bacterial or chronic tuberculous
      meningitis. Involvement of major cerebral vessels is rare and basilar artery
      thrombosis has not been reported in fungal meningitis secondary to candida
      infection. METHODS: We describe the clinical course and neuropathological
      findings in a woman with chronic meningitis due to Candida albicans. RESULTS: The
      diagnosis remained elusive antemortem despite analysis of 7 large volume CSF
      samples and examination of a meningeal and cortical biopsy. Death followed
      extensive brainstem and temporo-occipital infarction secondary to basilar artery
      thrombosis. The basilar artery occlusion was secondary to an intense,
      granulomatous and necrotizing basal meningitis focally extending to the media and
      intima. CONCLUSIONS: This paroxysmal and devastating complication of untreated
      chronic candida meningitis reinforces that a trial of empirical therapy with both
      antituberculous and antifungal agents should be considered in most cases of
      chronic culture-negative lymphocytic meningitis.

PMID- 9532287
TI  - Severe tension pneumocephalus complicating frontal sinus osteoma.
AB  - BACKGROUND: Tension pneumocephalus, the accumulation of intracranial gas under
      pressure, is a rare but potentially life-threatening condition which can
      complicate craniofacial surgery, trauma, or cranial tumor. It presents as an
      acute or subacute expanding mass lesion. CASE REPORT: We present a case of a 40
      year-old male who developed tension pneumocephalus as a consequence of a
      previously detected but untreated frontal sinus osteoma. Despite prompt
      decompression and repair of the fistulous connection between the sinus and the
      intracranial compartment, the patient suffered permanent frontal lobe damage with
      significant neurocognitive sequelae and seizures. CONCLUSIONS: This case
      illustrates that tension pneumocephalus can be a dangerous entity with potential
      for early mortality and long-term morbidity. We recommend, therefore, early
      treatment and close follow up of destructive lesions involving the posterior
      frontal sinus wall.

PMID- 9532288
TI  - Parkinsonian syndrome as a neurological manifestation of Behcet's disease.
AB  - BACKGROUND: The central nervous system is often involved in Behcet's disease.
      Most common are meningoencephalitic and brain stem syndromes. Although basal
      ganglia involvement is not an uncommon finding on necropsy, there are only single
      reports on extrapyramidal syndromes-dyskinesia, chorea and Parkinsonism in
      patients with Behcet's disease. CASE STUDY: We report a patient fulfilling the
      criteria of the International Study Group for Behcet's disease. He had recurrent
      oral ulcerations, bilateral posterior uveitis and retinal vasculitis, skin
      papules and pustules, and recurrent monoarthritis. Neurologic examination
      revealed pseudobulbar palsy, slight and asymmetric bilateral pyramidal syndrome,
      muscle rigidity involving the four limbs, bradykinesia, masked face, and impaired
      postural reflexes. There was postural tremor in the extremities and myoclonic
      jerks involving the tongue and face muscles. Magnetic resonance imaging
      demonstrated small bilateral multifocal hyperintense lesions, with right
      predilection, involving the periventricular white matter, brain stem and basal
      ganglia. CONCLUSIONS: The Parkinsonian syndrome found in our patient might be due
      to involvement of both substantia nigra and basal ganglia. This case further
      emphasizes the wide spectrum of the neurological manifestations of Behcet's
      disease.

PMID- 9532289
TI  - Management of status epilepticus.
AB  - The pharmacologic management of major motor status epilepticus is summarized.
      When general anesthesia is required, the electroencephalogram (EEG) is used for
      monitoring the adequacy of treatment. The EEG findings may also be important in
      recognizing status epilepticus and monitoring its response to treatment when this
      is clinically difficult, as when it occurs in comatose or pharmacologically
      paralyzed patients or in the context of severe brain damage. Finally, the EEG
      helps to clarify the nature of motor activities of uncertain basis in patients in
      the intensive care unit and has indicated that non-convulsive seizures or status
      are more common than clinically suspected in such patients.

PMID- 9532290
TI  - Monitoring severe head injury: a comparison of EEG and somatosensory evoked
      potentials.
AB  - We report on our experience with long-term monitoring of the EEG power spectrum
      and somatosensory evoked potentials (SSEPs) in 103 patients with severe closed
      head injury (Glasgow Coma Scale-GCS < or = 8). Patients were monitored for an
      average of 5 days post injury and monitoring was terminated when they died,
      regained consciousness or their intracranial physiologic parameters (primarily
      intracranial pressure-ICP) were stable for 2-3 days. Patients were treated
      according to a standard protocol that included mechanical ventilation, sedation,
      and neuromuscular blockade. At 7 of 9 twelve hour time intervals post injury,
      SSEPs were significantly (p < .05) different between outcome groups using the
      Glasgow Outcome Score collapsed to 3 categories. The percent slow (delta)
      activity in the EEG was not significantly different between outcome groups at any
      time point, post injury. The total power in the EEG power spectrum differed only
      at the last time epoch post injury (108 hr.). Based on the superior prognostic
      capabilities of the SSEP, we routinely base critical management decisions on SSEP
      values. We have not been able to rely on EEG parameters for these same decisions
      due to the lack of clear distinction between good and poor prognosis groups based
      on common EEG parameters.

PMID- 9532291
TI  - Continuous EEG monitoring in the intensive care unit.
AB  - BACKGROUND: Electroencephalography (EEG) is playing an increasingly important
      role in the management of comatose patients in the intensive care unit. METHODS:
      The techniques of EEG monitoring are reviewed. Initially, standard, discontinuous
      recordings were performed in intensive care units (ICUs). Later, continuous
      displays of "raw EEG" (CEEG) were used. More recently, the addition of
      quantitative techniques allowed for more effective reading. RESULTS AND
      CONCLUSIONS: Applications of continuous EEG to clinical problems are discussed.
      The most useful role of CEEG appears to be the detection and management of
      nonconvulsive seizures. There is a need for controlled studies to assess the role
      for CEEG in neuro-ICUs and general ICUs.

PMID- 9532292
TI  - Metabolic and inflammatory cerebral diseases: electrophysiological aspects.
AB  - The electroencephalogram (EEG) is an important diagnostic tool in coma. Although
      comatose patients may be similar on neurological examination, the EEG reveals a
      wide range of abnormalities. For metabolic and septic encephalopathies, the
      "anesthesia model" is a useful analogy. The EEG is very sensitive to the depth or
      severity of brain dysfunction in coma as well as the direction of the process if
      serial tracings or continuous recordings are used. While the EEG is rarely
      specific for the etiology of coma, it may help determine the class or general
      category of disease process. In conditions capable of causing neuronal death,
      e.g., anoxia-ischemia, the EEG can be of prognostic value.

PMID- 9532293
TI  - Electrophysiological respiratory studies in the critical care unit.
AB  - Respiratory electrophysiological studies are useful in the investigation and
      monitoring of respiratory failure. Phrenic nerve conduction studies and needle
      electromyography of the diaphragm are invaluable in establishing the diagnosis,
      determining the severity, and following the progression of peripheral respiratory
      muscle dysfunction. In addition to these established methods, repetitive phrenic
      nerve stimulation is of diagnostic value in patients with neuromuscular
      transmission defects and dyspnea. The diagnosis of impaired central respiratory
      drive can often be accomplished by the newly-developed techniques of
      transcortical magnetic stimulation of the motor cortex with recording of the
      diaphragm and phrenic nerve somatosensory evoked potentials. These studies are of
      particular value in critically ill patients where both the central and peripheral
      lesions may impair respiration.

PMID- 9532294
TI  - Quantitation in EMG.
AB  - The neuromuscular system may be affected by disorders of the central nervous
      system as well as other disorders affecting motoneurons, axons, neuromuscular
      transmission, the sarcolemmal membrane, the contractile elements and other
      components of the muscle fibers themselves. One or a combination of these
      possibilities can present in patients in the critical care unit. This paper
      reviews various qualitative and quantitative methods for assessing the various
      components of the peripheral contributions to the electrical and force output as
      well as the central motor drive to motoneurons. These methods all have their own
      strengths and weaknesses but many are complementary and together, can provide
      important diagnostic and prognostic information to guide management.

PMID- 9532295
TI  - Electrophysiological studies in the critical care unit: investigating
      polyneuropathies.
AB  - Polyneuropathies frequently contribute to ventilator dependency and prolonged
      stay in the intensive care unit. As clinical examination is often limited in
      critically ill patients, electrophysiological studies are invaluable in
      establishing the diagnosis of neuropathy, determining its pathophysiology,
      severity and in following the patients' progression. Guillain-Barre syndrome
      (GBS) developing before intensive care unit admission and critical illness
      polyneuropathy (CIP) developing as a complication of sepsis and multiorgan
      failure are the commonest causes of neuropathy. Electrophysiological findings in
      CIP are that of an axonal neuropathy whereas the findings in GBS are usually
      consistent with a demyelinating neuropathy. Axonal GBS can be distinguished from
      CIP by the preceding illnesses, slow nerve conduction velocity in some cases,
      lack of spontaneous activity on the initial needle electromyographic study and
      cerebrospinal fluid findings.

PMID- 9532296
TI  - Methods of testing neuromuscular transmission in the intensive care unit.
AB  - All disorders of neuromuscular transmission (NMT) may cause ventilatory failure,
      albeit rarely. Respiratory muscle weakness is occasionally the presenting feature
      of myasthenia gravis (MG), the Lambert-Eaton myasthenic syndrome (LEMS),
      hypermagnesemia and botulism. Chronic MG, congenital myasthenic syndromes and
      LEMS may be acutely exacerbated by various intercurrent conditions and by drugs
      which interfere with NMT. Finally, in the ICU, difficulty in weaning from the
      ventilator may be caused by prolonged use of neuromuscular blocking agents.
      Electrophysiological studies of NMT disorders in the intensive care unit have
      rarely been reported. Nevertheless, the available data indicates that the
      electrodiagnosis of severe NMT disorders can be misleading. With severe NMT
      defects, the electrophysiological distinction between post-synaptic and pre
      synaptic disorders is blurred and the differential diagnosis with myopathies may
      be difficult. A clinically suspected NMT disorder should therefore not be ruled
      out when electrodiagnosis fails to demonstrate the expected abnormalities.

PMID- 9532297
TI  - Myopathies in the intensive care unit.
AB  - Myopathies that occur in the intensive care unit can be divided into preexisting
      myopathies or newly acquired myopathies that develop in the intensive care unit.
      Myotonic dystrophy is an example of a preexisting myopathy that may render
      patients susceptible to acute respiratory failure following surgical procedures
      and anaesthesia. A group of myopathies that develop within the intensive care
      unit have been labelled acute necrotizing myopathy of intensive care, thick
      filament myopathy and acute steroid myopathy. Corticosteroids and nondepolarizing
      muscle blocking agents may play a role in their development.

PMID- 9532298
TI  - Typhoid ileal perforation: the value of delayed primary closure of abdominal
      wounds.
AB  - Twenty-four patients with typhoid perforation of the terminal ileum operated on
      over a period of 1 year were studied to evaluate delayed primary closure of
      abdominal wounds. Twenty patients with the same diagnosis had primary wound
      closure to serve as control. Over 80% of the patients were between 1st and 3rd
      decades of life. The male:female ratio was 3:1 to 4:1. Mean duration of symptoms
      was 9.83 and 11.25 days while that of peritonitis was 2.87 and 2.50 days for the
      study and control groups, respectively. Terminal ileal perforations were
      confirmed in all and mean volume of pus and faeculent peritoneal fluid were 529
      ml and 482 ml, respectively. Wound infection occurred in 70.8% and 70% of the
      study and control groups, respectively. Other complications such as wound
      dehiscence occurred in 37.5% and 35%, residual intraabdominal abscess in 8.3% and
      10%, and faecal fistula in 8.3% and 10% of the study and control groups,
      respectively. Mortality was in 25% and 20%, respectively. The above results
      suggest that delayed primary closure has no value in preventing abdominal wound
      infection in typhoid perforation.

PMID- 9532299
TI  - Clinical pattern of human immunodeficiency virus infection (HIV) in pulmonary
      tuberculosis patients in Jos, Nigeria.
AB  - A study of determine the seroprevalence rate and clinical presentation of HIV
      associated pulmonary tuberculosis was carried out in Jos between October 1990 and
      September 1991. Out of the 180 newly diagnosed pulmonary tuberculosis patients,
      11(6.1%) were confirmed seropositive for HIV-1 and 2. The peak age range for both
      tuberculosis and HIV infection in both sexes is 20-40 years. The risk of HIV
      infection was associated with multiple sex partners and blood transfusion. There
      was no significant difference in the clinical presentation of pulmonary
      tuberculosis between HIV-seropositive and seronegative patients (P > 0.1).
      However, diarrhoea, lymphadenopathy and marked weight loss were found to be
      significantly associated with HIV infection (P < 0.05). The mean lymphocyte count
      of HIV seropositives was significantly lower than seronegatives (P < 0.01).

PMID- 9532300
TI  - Canine filariasis in Zaria, Nigeria.
AB  - Microscopic examination of blood samples from dogs in Zaria, Nigeria indicated
      the prevalence of canine filariasis to be 12.7%. The survey demonstrated three
      species of canine filariae, namely D. repens (8.9%). D. immitis-like parasite
      (2.5%), and an unidentified species of filaria with a prevalence of 4.4%.

PMID- 9532301
TI  - Serum total, heat and urea stable alkaline phosphatase activities in relation to
      ABO blood groups and secretor phenotypes.
AB  - The relationship between serum alkaline phosphatase (AP) isoenzymes, ABO blood
      groups and secretor phenotypes was evaluated in 125 Nigerian voluntary blood
      donors. The serum total AP activity patterns were group O > Group B > Group AB >
      Group A, but only the differences between A/B, A/O and AB/O were significant. The
      total and activities of the different isoenzymes were lowest in group A, while
      highest values were found in group O. The different activities for group AB were
      intermediate between the levels for A and B. The activities of the different
      isoenzymes tended to be higher in secretors than in non-secretors. Our results
      may suggest that both the blood group and secretor genes are strong determinants
      of AP isoenzyme patterns in Nigeria.

PMID- 9532302
TI  - The prevalence of toxoplasma antibodies in pregnant Nigerian women and the
      occurrence of stillbirth and congenital malformation.
AB  - Toxoplasma antibody serological tests were carried out using the Dye test on sera
      of pregnant and postpartum Nigerian women to investigate whether there was any
      association between the levels of antibody titres and the occurrence of
      stillbirths and congenital malformations. There was a high prevalence of
      toxoplasma antibodies in the sera of both pregnant and postpartum women. The
      prevalence rates for the pregnant women ranged from 72.5% to 88.8% with an
      overall rate of 75.4%; whilst for the postpartum women, the prevalence rates
      ranged from 75.0% to 94.4% with an overall rate of 80.5%. The toxoplasma antibody
      titres of the sera from the live-born babies as well as stillbirths and
      congenitally malformed babies ranged from 1:16 to 1:1024. The exact role played
      by toxoplasma in the occurrence of stillbirths and congenital malformation in our
      area of study is, however, not clear. For future research, it is suggested that
      larger samples be studied in order to enhance the validity of the findings of the
      present study.

PMID- 9532303
TI  - Arterial pressure and lipid profile in rats following chronic ingestion of palm
      oil diets.
AB  - The mean arterial blood pressure (MAP) and plasma lipid profile of rats following
      chronic consumption of a diet containing 15% palm oil (fresh or oxidized) were
      studied. Rats were allowed to feed on either a fresh or oxidized palm oil diet
      for 18 weeks and their effects were compared with a control group receiving
      normal rat feed. Mean arterial blood pressures were 128.0 +/- 2.3 mmHg (mean +/-
      SEM) for the control, 135.0 +/- 2.4 mmHg for the fresh-oil fed group and 147 +/-
      2.5 mmHg for the oxidized oil-fed group. The oxidized oil-fed group had a
      significantly greater rise in mean arterial blood pressure than the control and
      fresh oil-fed groups (P < 0.01 and 0.05, respectively). Mean arterial blood
      pressure was not significantly elevated in the fresh oil-fed group than the
      control. Low density lipoprotein cholesterol (LDL) levels were 1.51 +/- 0.07
      mMol/L for the control, 1.62 +/- 0.03 mMol/L for the fresh oil-fed group and 1.78
      +/- 0.03 mMol/L for the oxidized oil-fed group. The values were not significantly
      different in the control and the fresh oil groups. LDL level was significantly
      higher in the oxidized than in the control (P < 0.01) and fresh oil-fed groups (P
      < 0.05). Total cholesterol for the two test groups were significantly (P < 0.05)
      higher than the control, while the value in the oxidized oil group was also
      significantly (P < 0.05) higher than the fresh oil-fed group. There was no
      significant difference in high density lipoprotein cholesterol (HDLP) levels in
      the three groups. The significantly elevated MAP in the oxidized oil-fed rats
      when compared to the fresh oil-fed and control rats may be due to thermoxidation
      of the fresh oil that produced significantly higher levels of LDL and total
      cholesterol which predisposes to high blood pressure.

PMID- 9532304
TI  - Profile of some risk factors for coronary heart disease in a developing country:
      Nigeria.
AB  - The profile of some risk factors for coronary heart disease was studied in 557
      male and 325 female Nigerians aged 20 years and above from the low and medium
      income groups, respectively. Except for the weight of subjects in the low income
      level, values of all physical characteristics were significantly higher in
      females than males (P < 0.01). In the 20-39 years age group, the systolic blood
      pressure was higher in males than females, and among the medium income group than
      the low income group (P < 0.01); but this difference disappeared in the higher
      age groups. The mean diastolic blood pressure was higher (but not statistically
      significant) at medium income levels than low income levels (P > 0.05). In each
      age group, the mean plasma total cholesterol was significantly higher in the
      medium income group than in the low income group (P < 0.01). The percentage of
      smokers and alcohol consumers were higher in the high income group than the low
      income group (P < 0.01). A high percentage of the smokers and alcohol consumers
      were male subjects. Blood pressure was correlated with age, smoking and body fat,
      (P < 0.01). Waist to trochanter ratio, and percentage body fat were significantly
      related to plasma total cholesterol level (P < 0.01).

PMID- 9532305
TI  - The immune response of Trypanosoma gambiense-infected mice to Schistosoma whole
      worm antigens.
AB  - Heterologous humoral and cellular immune response to Schistosoma mansoni and S.
      bovis antigens were investigated in Tryponosoma gambiense-infected mice in order
      to understand the concurrent immune response to both parasites. Immune response
      as measured by the Indirect Haemagglutination Test (IHA), Spontaneous sheep red
      blood cell rosette formation with B-lymphocytes and the mean number of T
      lymphocytes forming rosettes with AET-treated SRBC to the schistosome antigens,
      was significantly depressed in the trypanosome-infected mice. Furthermore, the
      timing of trypanosome infection and the inoculation of antigen was related to the
      degree of immunosuppression as animals which had trypanosome infection and the
      whole worm antigen of S. mansoni and S. bovis simultaneously had higher IHA titre
      than those which were inoculated with the antigens 10 days after the commencement
      of an infection. The results are discussed from the viewpoint of immunological
      control of schistosomiasis in areas where both diseases are endemic.

PMID- 9532307
TI  - Effect of social class on the prevalence and severity of necrotising ulcerative
      gingivitis in Nigerian children.
AB  - A study was designed to determine the relationship of social class to the
      prevalence of necrotising ulcerative gingivitis (NUG) and its severity. The study
      cohort was made up of 438 consecutive under 12-year old children attending Dugbe
      Dental Centre in Ibadan, Nigeria. They were assessed by history taking and intra
      oral examination using a dental probe and dental mirror. A modification of the
      social class criteria of Olojugba and Lenon (1987) was used to determine the
      social class of the children. An index was also developed for NUG severity. The
      prevalence of NUG in the study cohort was 27.4%. The results showed a strong
      association between the prevalence and severity of NUG and social class (X2 46.75
      P < 0.001).

PMID- 9532306
TI  - Closed chest drainage without an underwater seal.
AB  - Six hundred and eighty-five patients requiring pleural drainage were referred to
      and managed by the Cardiothoracic Unit of the University College Hospital, Ibadan
      between June 1985 and September 1992. Two hundred patients, in which Aldon's
      urobag (e.g. Simpla S4 type) was used for pleural drainage were studied. The
      indications for pleural drainage were pyothorax or pyopneumothorax (106
      patients), malignant pleural effusion (53 patients), tuberculous effusions (23
      patients) and chest trauma (18 patients). In seven of these patients, the Aldon's
      urobag was used for out-patient care pleural drainage. Some of the reasons for
      discontinuing its use were major tracheobronchial injuries (2 patients), clotted
      haemothorax (5 patients), chronic empyema thoracis (10 patients) and loculated
      malignant pleural effusions. The few easily surmountable complications
      encountered were obstruction of the tube by blood clot and fibrinous coagulate,
      stoma necrosis and periosteal reaction. The advantages observed from the use of
      Aldon's urobag for pleural drainage were reduction in cost of pleural drainage,
      availability of this drainage system and its use for out-patient care when
      indicated.

PMID- 9532308
TI  - Radiological evaluation of orbital tumours in Ibadan, Nigeria.
AB  - Tissue diagnosis of orbital tumours is especially difficult because of the wide
      range of tissues normally occurring in the orbit [2]. Unfortunately, such tumours
      are relatively surgically inaccessible for biopsy due to the presence of the bony
      walls of the orbit and its peculiar shape. This gives rise to a need for
      effective methods of indirect assessment of the orbit and its contents prior to
      definitive therapy. Such indirect assessment may be achieved using certain
      modalities of radiological imaging. These include conventional plain X-ray films,
      ultrasound scan (USS) and computerized axial tomography (CAT scan), orbital
      venography and magnetic resonance imaging. This paper is a pilot study of current
      practices in the use of radiological imaging techniques in the diagnosis of
      orbital tumours at a University Hospital.

PMID- 9532309
TI  - Acyl-coenzyme A: cholesterol- acyl-coenzyme A:1,2-diacylglycerol acyltransferase
      and phosphatidate phosphorylase activities in liver microsomes from nephrotic
      rats.
AB  - The lipid components of very low density lipoproteins (VLDL) were significantly
      elevated in the nephrotic rats. Also the nephrotic VLDL particles had a
      significantly higher ratio of surface lipids (FC + PL) to core lipids (TG + CE)
      probably indicating production of smaller sized VLDL in the nephrotic rats.
      Electron microscopy showed VLDL particles with a reduced mean size in the
      nephrotic rats. The activities of VLDL core lipid synthesizing enzymes were
      evaluated in experimental nephrotic syndrome. In addition, the effects of
      exogeneous cholesterol, 25-OH-cholesterol and low density lipoprotein (LDL) on
      the acyl-coenzyme A: cholesterol acyltransferase (ACAT) activity were
      investigated as well. ACAT activity in nephrosis was normal, but stimulated to
      varying extents in the presence of these factors. On the other hand, the
      acylcoenzyme A:1,2-diacylglycerol acyltransferase (ADGAT) and phosphatidate
      phosphorylase-activities were significantly increased in the nephrotic rats. The
      microsomal cholesterol (free and ester) and phospholipid concentrations were
      normal but the triglyceride level was significantly reduced in the experimental
      group. We speculate that an excess production of smaller-sized VLDL particles due
      to altered activities of microsomal lipid synthesizing enzymes may occur in
      puromycin amino nucleoside induced-nephrotic rats.

PMID- 9532310
TI  - Antimicrobial activity of some medicinal plants extracts on Escherichia coli,
      Salmonella paratyphi and Shigella dysenteriae.
AB  - The antimicrobial activity of three plants extracts--Momordica charantia,
      Alstonia boonei, and Ocimum bacilicum on pure and viable cultures of Escherichia
      coli, Salmonella paratyphi and Shigella dysenterae was examined. Cold maceration
      method of extraction using 95% ethanol was used for the extraction of the active
      constituents of the leaves. Filter paper disks which were 6 mm in diameter were
      used for sensitivity testing. Results showed that the extracts from the leaves of
      the three plants have some antimicrobial properties against the test organisms
      which suggest their future possible commercial therapeutic use, although this is
      a preliminary study.

PMID- 9532311
TI  - Influence of mode of delivery on twin births.
AB  - The mode of delivery and outcome in 158 twin births in a Nigerian sub-urban
      hospital are reviewed. Apgar scores at one minute were significantly higher for
      twin 1 compared to twin 2 in vertex deliveries only. There was no significant
      difference in Apgar scores at 5 minutes between the twins for the various modes
      of delivery. Apgar scores were generally higher for the controls (a set of
      singleton births) compared to twin births for all the modes of delivery except
      breech births. Birth weights were also significantly higher for controls compared
      to twin births although no significant difference occurred between the twins.
      Perinatal mortality rates were generally higher for twin 2 compared to twin 1,
      and for the twins compared to controls irrespective of mode of delivery. Better
      outcome could not be ascribed to any particular mode of delivery in twin births
      and would depend on the judgement and expertise of the labour attendant.

PMID- 9532312
TI  - A simple and sensitive microtiter plate estrogen bioassay based on stimulation of
      alkaline phosphatase in an endometrial adenocarcinoma cell line (Ishikawa line).
AB  - We have developed an estrogen bioassay using the Ishikawa human endometrial
      adenocarcinoma cell line grown in 96-well microtiter plates. Alkaline phosphatase
      enzyme activity (Alkp) in these cells was markedly stimulated by estrogen (E2),
      and this enzyme can be easily quantified in situ using a chromogenic substrate.
      Estradiol induces AlkP at levels as low as 10-8M. The induction of AlkP is
      specific for estrogens as for other steroids and other steroidal materials
      (Progesterone, Tamoxifen, clomiphene citrate, Ru 486, ICI) could not produce a
      similar effect. The stimulation of AlkP in Ishikawa cells is not only specific
      for estrogen, it is highly reproducible and sensitive and permits large numbers
      of samples to be assayed with ease. The non-radioactive nature of the assay makes
      it attractive to developing countries.

PMID- 9532313
TI  - Fractures of the facial skeleton in Tabuk North West Armed Forces Hospital: a
      five year review.
AB  - A five-year review of nine hundred and eighty maxillofacial injuries seen and
      treated at the Armed Forces Hospital, Tabuk, Saudi Arabia is presented. The
      dominant age group range was 21-30 years. There were almost twice as many
      maxillary fractures as mandibular fractures. The most common aetiology was road
      traffic accidents (RTA), followed by sport traumas. Facial lacerations and
      contusions followed by neurologic and orthopaedic injuries were the most common
      concomitant injuries.

PMID- 9532314
TI  - A ten-year review of asthma deaths at the Lagos University Teaching Hospital.
AB  - A retrospective study was made of forty-nine patients certified as dying from
      asthma in order to identify potentially avoidable factors. Forty-nine per cent of
      the deaths were due to delay in seeking medical help by patients or relations.
      Other factors identified as contributing to the asthma deaths included inadequate
      objective assessment of airway function, as well as inadequate administration of
      corticosteroids. Education of patients and general practitioners, as well as
      speedy referral to specialized units will help reduce the gap between diagnostic
      and therapeutic knowledge and its application in a developing country like
      Nigeria.

PMID- 9532315
TI  - Hypertension and peri-operative stroke.
AB  - A 67-year-old adult male with borderline hypertension who had extracapsular
      cataract extraction under general anaesthesia is reported. There were marked
      fluctuations in his arterial blood pressure following induction of anaesthesia
      and during the recovery period. He developed a stroke in the immediate
      postoperative period but was fully recovered after 3 weeks. This case illustrates
      some of the potentially preventable factors that can predispose to stroke in
      undiagnosed or poorly controlled hypertensive patients. Such cases are commonly
      presented to anaesthetists in developing countries where the availability of
      monitoring equipments, anaesthetic drugs and agents is highly limited.

PMID- 9532316
TI  - Neurological manifestations of chronic myelogenous leukaemia.
AB  - Neurological manifestations occur in about one-quarter of patients with chronic
      myelogenous leukaemia (CML), usually as a result of hyperleukocytosis,
      predisposing to intravascular thrombus formation. We report the clinical and
      pathological findings in a 16-year-old female with CML who presented with
      deafness, blindness and paraplegia, and discuss possible aetiopathogenetic
      mechanism.

PMID- 9532317
TI  - Gustatory sweating in the differential diagnosis of food allergy.
AB  - Herein reported is a 41-year-old white man with lifelong gustatory sweating over
      the vertex of the head induced by orange juice, tomatoes, onions, and certain
      nonchocolate candies and snack foods. IgE RAST and prick tests were negative to
      those offending foods for which test antigens were available. The types of
      gustatory sweating and their therapeutic modalities are summarized.

PMID- 9532318
TI  - Clinical study of yoga techniques in university students with asthma: a
      controlled study.
AB  - Adult asthmatics, ranging from 19 to 52 years from an asthma and allergy clinic
      in a university setting volunteered to participate in the study. The 17 students
      were randomly divided into yoga (9 subjects) and nonyoga control (8 subjects)
      groups. The yoga group was taught a set of breathing and relaxation techniques
      including breath slowing exercises (pranayama), physical postures (yogasanas),
      and meditation. Yoga techniques were taught at the university health center,
      three times a week for 16 weeks. All the subjects in both groups maintained daily
      symptom and medication diaries, collected A.M. and P.M. peak flow readings, and
      completed weekly questionnaires. Spirometry was performed on each subject every
      week. Analysis of the data showed that the subjects in the yoga group reported a
      significant degree of relaxation, positive attitude, and better yoga exercise
      tolerance. There was also a tendency toward lesser usage of beta adrenergic
      inhalers. The pulmonary functions did not vary significantly between yoga and
      control groups. Yoga techniques seem beneficial as an adjunct to the medical
      management of asthma.

PMID- 9532319
TI  - Laryngeal papilloma presenting as steroid-dependent asthma in a 3-year-old child
      without recurrent stridor.
AB  - Upper airway obstruction is well described as a cause of apparent asthma.
      However, it can be very difficult to diagnose in young children. This 3-year-old
      male presented with a 1-year history of severe recurrent wheezing with six
      emergency room visits in the previous 5 months. Cromolyn, inhaled
      corticosteroids, and frequent predinisolone bursts had not controlled the
      wheezing. There was no history of barky cough, croup, or stridor. His physical
      examination was notable for marked nasal obstruction. At initial presentation,
      his lungs were normal with no wheezing or stridor. Soft tissue neck X-ray films
      suggested the presence of a subglottic mass. A large solitary papilloma was found
      on bronchoscopy. After surgical removal, there was no further wheezing noted by
      either the parents or his physicians. Laryngeal papillomatosis may mimic asthma
      in the absence of symptoms of hoarseness, croup, or stridor. It should be
      particularly considered in 2 to 4-year-old children with recurrent wheezing that
      is poorly responsive to aggressive therapy including oral corticosteroids.

PMID- 9532321
TI  - The anticholinergic agent, ipratropium bromide, is useful in the treatment of
      rhinorrhea associated with perennial allergic rhinitis.
AB  - The effects of the new ipratropium bromide nasal spray on rhinorrhea associated
      with perennial allergic rhinitis were studied in 219 patients over eight weeks in
      a multicenter, randomized, double-blind trial. The purpose of the study was to
      determine whether the new spray reduces nasal hypersecretion in allergic patients
      without causing excessive dryness or other potential cholinergic side effects.
      The investigators compared two doses of the spray (42 or 84 mcg/nostril t.i.d.)
      to placebo. Two hundred and nineteen patients were admitted to the study; 176
      completed it. Study design included one week of screening to confirm a diagnosis
      of perennial allergic rhinitis with clinically significant rhinorrhea, one week
      of single-blind treatment with a placebo consisting of the saline vehicle of the
      spray, an eight-week double-blind treatment-comparison period, and one week of
      follow-up without treatment. Both doses of ipratropium bromide nasal spray
      significantly reduced the hypersecretion associated with PAR, compared with
      placebo. The two doses of active drug were equally effective. Treatment
      differences were noticeable during the first week and remained relatively stable
      during the eight-week treatment period. There was no evidence of nasal rebound
      after discontinuation of treatment. The incidence of side effects was comparable
      to placebo. The spray was well-tolerated, and was not associated with any
      significant adverse events.

PMID- 9532320
TI  - Epithelial cells are a major cellular source of the chemokine eotaxin in the
      guinea pig lung.
AB  - Eotaxin is the major eosinophil chemoattractant found in bronchoalveolar lavage
      (BAL) fluid from sensitized guinea pigs after antigen challenge. In this study we
      have performed immunostaining for eotaxin in airways obtained from challenged
      animals and examined purified guinea pig lung cells (epithelial cells > 98%
      purity, mast cells > 90% purity) for eotaxin mRNA and protein. In the airways of
      antigen (ovalbumin) challenged animals, significant amounts of epithelial cell
      eotaxin immunostaining were observed. Northern analysis of total RNA obtained
      from unchallenged, freshly isolated airway epithelial cells contained high levels
      of eotaxin mRNA. Semi-pure and high purity lung mast cell preparations
      (challenged or unchallenged) did not express eotaxin mRNA. Western analysis of
      supernatant fluids obtained from incubated airway epithelial cells demonstrated
      detectable amounts of eotaxin protein, with the majority of the protein being
      cell-associated. Thus, airway epithelial cells are identified as a major cellular
      source of eotaxin in the guinea pig pulmonary system.

PMID- 9532322
TI  - Asthma among the famous. Ernest W. Hornung (1866-1921), British author.

PMID- 9532323
TI  - Asthma among the famous. Marcel Proust (1871-1922), French author.

PMID- 9532324
TI  - Asthma among the famous. J. Calvin Coolidge (1872-1933). Thirtieth president of
      the United States.

PMID- 9532325
TI  - Asthma among the famous. Arnold Schoenberg (1874-1951). Austrian-American
      composer.

PMID- 9532326
TI  - [Comparative activity of meropenem and other antibiotics against the pathogens of
      nosocomial infections].
AB  - Comparative activity of meropenem and other antibacterial drugs against isolates
      from intensive care and reanimation units of various profiles was estimated. It
      was shown that the recommendations for the combined therapy with the 3rd
      generation cephalosporins and aminoglycosides should be revised, since none of
      the isolates resistant to ceftazidime or cefotaxime was susceptible to gentamicin
      or tobramycin. At present the most promising agents of empirical therapy are
      carbapenems (meropenem and imipenem). However, the resistance of methicillin
      resistant staphylococci and Enterococcus faecium to carbapenems and the intrinsic
      resistance of some gram-negative bacteria to carbapenems are indicative of the
      necessity of microbiological diagnosis, especially when the treatment with
      meropenem fails.

PMID- 9532327
TI  - [Multicenter open randomized trial of meropenem in comparison to ceftazidime and
      amikacin used in combination in severe hospital infections].
AB  - Clinical efficacy and tolerance of meropenem were estimated by comparison with
      those of ceftazidime and amikacin used in combination in the therapy of hospital
      infections of the lower respiratory tract, skin and soft tissues, intraabdominal
      and gynecologic infections, urinary tract infection and sepsis. 48 patients were
      given meropenem in a dose of 1 g every 8 hours for 3-14 days (the average of 9
      days). 47 patients were subjected to the routine combined therapy: ceftazidime in
      a dose of 1 g every 8 hours and amikacin in a dose of 0.5 g every 12 hours for 2
      14 days (the average of 9 days). The patient groups were comparable by the age,
      nature and severity of the infection and the condition (the mean APACHE II of 9.1
      and 8.9). By the end of the treatment a positive clinical effect (recovery and
      improvement) was observed in 47 patients (97.9 per cent) treated with meropenem
      and in 41 patients (89.1 per cent) subjected to the combined therapy. The
      infection relapse within 4 weeks after the treatment completion was recorded in 3
      patients in every group. Before the treatment 133 microbial strains were isolated
      from the patients. 121 of them were susceptible to meropenem (91.1 per cent), 111
      to amikacin (83.4 per cent) and 90 to ceftazidime (67.7 per cent). The difference
      between meropenem and ceftazidime was significant (p = 0.0005). Eradication of
      the primary pathogens at the background of the meropenem therapy was stated in 41
      out of 44 patients (93.2 per cent) and that of the combined therapy in 38 out of
      43 patients (88.4 per cent). The microbiological relapse after the treatment
      completion was recorded in 3 and 2 patients, respectively. Side effects were
      observed in 8.3 per cent of the patients treated with meropenem and in 10.6 per
      cent of the patients subjected to the combined therapy. The trial results were
      indicative of the meropenem high efficacy and good tolerance and of the possible
      use of the drug in the monotherapy as an alternative of the routine combined
      therapy of severe hospital infections.

PMID- 9532328
TI  - [Effectiveness of the new carbapenem antibiotic, meropenem, in adult patients
      with mucoviscidosis].
AB  - Clinical efficacy of meropenem (meronem, Zeneca), a new carbapenem, was studied
      in the treatment of 4 adult patients with mucoviscidosis. The drug was
      administered as intravenous infusions 3 times a day in a daily dose of 60 mg/kg
      body weight for 10 days. A positive clinical effect was observed in 3 patients
      and in 1 patient stabilization of the clinical state was recorded. A significant
      decrease in the titre of the Pseudomonas aeruginosa colonies in 2 patients and
      that of the P. aeruginosa mucosa colonies in 3 patients was bacteriologically
      confirmed. Good tolerance and no side effects of meropenem in the doses used were
      stated. The study showed that meropenem may be recommended for the treatment of
      adult patients with mucoviscidosis.

PMID- 9532329
TI  - [Use of meropenem in patients with neutropenia].
AB  - Meropenem was used in the treatment of 14 infectious complications in 11 patients
      including 8 with acute myeloid leukemia due to the cytostatic therapy, 1 with
      chronic myeloid leukemia, 1 with aplastic anemia and 1 with acute intermittent
      porphyria. At the moment of the meropenem use critical neutropenia (less than 500
      granulocytes per 1 ml) in 11 cases (79 per cent) was stated. The drug was
      administered as intravenous infusions in a dose of 1 g every 8 hours for 4 to 41
      days (the median of 11 days). 9 out of the 14 infectious complications were cured
      (the body temperature normalized and all the inflammation foci were eliminated),
      among them 6 out of 8 pyocyanic sepsis. Eradication of gram-negative bacteria was
      observed in 8 out of 10 cultures of the biological materials. No toxic
      complications or electrolytic disorders due to the drug use were recorded. The
      drug tolerance was good.

PMID- 9532332
TI  - [Meropenem (Meronem). Guides for intravenous use of meropenem (information for
      specialists)].

PMID- 9532331
TI  - [Meropenem (from foreign publications)].

PMID- 9532330
TI  - [Use of meropenem in the treatment of severe infections in newborns].
AB  - Meropenem was used in the treatment of 15 newborns (8 preterm) with sepsis,
      pneumonia or meningitis by intravenous infusion of 15-20 mg/kg daily divided to 3
      equal doses. Clinical improvement was achieved in all the cases. No side effects
      were recorded.

PMID- 9532333
TI  - The genetic susceptibility to Graves' disease.
AB  - Graves' disease (GD) develops as a result of a complex interaction between
      genetic susceptibility genes and likely environmental factors. Most
      epidemiological data support an important genetic contribution to the development
      of GD. The concordance rate of GD in monozygotic twins is 30-60% and in dizygotic
      twins 3-9%, and thyroid autoantibodies have been reported in up to 50% of the
      siblings of patients with GD. For many years now, HLA studies have consistently
      shown an increased frequency of HLA-DR3 in Caucasian patients with GD; but with
      only a risk ratio of 3-5. However, recent advances in human genome mapping
      techniques have enabled the study of many other candidate genes. Of these
      additional, non-HLA genes, only CTLA-4 has been consistently found to be
      associated with GD. Using a linkage based approach which only detects highly
      significant susceptibility genes we have recently reported preliminary results
      which demonstrated that a marker located approximately 25 cM from the TSH
      receptor gene on chromosome 14q31 is linked to GD and in the same vicinity as the
      IDDM-11 locus. Such results, if confirmed, may signal the presence of a gene
      family related to endocrine autoimmunity on chromosome 14q31.

PMID- 9532334
TI  - Understanding the thyrotropin receptor function-structure relationship.
AB  - The thyrotropin (TSH) receptor (TSHR) is a key protein in the control of thyroid
      function and a major thyroid autoantigen. Recently, molecular cloning of the
      receptor has been carried out and we now review the impact of this work on our
      understanding of the physiology and pathophysiology of the TSHR. Analysis of
      recombinant TSHR proteins expressed in prokaryotic and eukaryotic systems has
      indicated that post-translational processing is important for the formation of
      active receptors. Studies of TSHR glycosylation have shown that a 'mature' form
      of the receptor containing mainly complex-type sugar residues is principally
      involved in TSH and TSHR autoantibody (TRAb) binding. In addition, the processing
      of the TSHR peptide chain into two subunits observed with native TSHR has been
      confirmed using recombinant TSHR. However, despite considerable efforts in many
      laboratories, the binding site(s) for TSH and TRAb on the TSHR have not been well
      characterized as yet and lessons learned from the discovery of naturally
      occurring amino acid mutations of the TSHR confirm the complexity of the hormone
      and autoantibody binding sites. Future progress in producing large amounts of
      pure TSHR as well as monoclonal TRAbs, followed by crystallographic analysis of
      TSHR-TSH complexes and TSHR-TRAb complexes, should be helpful in providing a
      better insight into the relationship between TSHR structure and function.

PMID- 9532335
TI  - Cytokines and Graves' disease.
AB  - Cytokines are an extraordinarily diverse group of molecules, with pleiotropic and
      often overlapping effects. They are crucial to the autoimmune response, and, in
      particular, regulation of CD4+ and CD8+ T-cell function depends on the balance of
      cytokines produced during an immune response. It is also now clear that cytokines
      are produced by a wide array of cells, including the thyroid follicular cells
      (TFCs). Intrathyroidal lymphocytes produce a heterogeneous pattern of cytokines
      and we have summarized the likely effects of these. In Graves' disease, TFCs can
      themselves express immunologically important molecules as the result of cytokine
      stimulation and these could contribute to the perpetuation of the autoimmune
      process. In addition, cytokines have a number of generally inhibitory effects on
      thyroid hormone production which would tend to counter the stimulatory effects of
      thyroid-stimulating hormone receptor antibodies in Graves' disease.

PMID- 9532336
TI  - Retro-orbital autoimmunity.
AB  - What causes Graves' ophthalmopathy is still a mystery, but the disease process
      results from a complex interplay of genetic and environmental factors. Genes such
      as those encoding for human leukocyte antigens, cytokines or putative target
      antigens may determine a patient's susceptibility to the disease and the disease
      severity, but environmental factors may determine its course. During the last 5
      years, significant progress has been made towards a more in-depth understanding
      of the initiating events of the orbital immune process which occur in the context
      of autoimmune thyroid disease. Once established, the chronic inflammatory process
      within the orbital tissues appears to take on a momentum of its own. The work of
      many investigators has recently helped to extend our knowledge about the effector
      and target cells, and their reciprocal interaction, in the evolution and
      perpetuation of the orbital immune process. This chapter's focus is on the more
      recent aspects of retro-orbital autoimmunity, discussing new developments
      concerning orbital T-cell repertoires, candidate orbital antigens, potential
      target and effector cells, and their role in the extrathyroidal manifestations of
      autoimmune thyroid disease.

PMID- 9532337
TI  - Treating severe Graves' ophthalmopathy.
AB  - Most patients with Graves' disease have some evidence of ocular involvement, but
      this is commonly mild, requiring only local measures. A minority of patients (3
      5%) have severe Graves' ophthalmopathy, for which the three main treatment
      procedures are represented by high-dose glucocorticoids, orbital radiotherapy and
      orbital decompression. Favourable results with medical treatment have been
      reported in approximately 60% of patients, with particular regard to inflammatory
      changes, newly developed eye muscle dysfunction and optic neuropathy. Orbital
      decompression is indicated in severe eye disease not responsive to
      glucocorticoids and/or irradiation, particularly in the presence of marked
      proptosis and optic neuropathy. Not conclusive or unsatisfactory results have
      been obtained with other medical treatment procedures, including
      immunosuppressive drugs, intravenous immunoglobulins and plasmapheresis. Recently
      favourable responses have been reported with somatostatin analogues.
      Rehabilitative surgery involving either the eye muscles or the eyelids is not
      infrequently required after medical treatment or decompression. Permanent control
      of thyroid hyperfunction by radioiodine or thyroidectomy is advisable when severe
      ophthalmopathy is present. Exacerbation of ophthalmopathy following radioiodine
      may occur but can be prevented by concomitant administration of glucocorticoids.
      Smoking deleteriously influences the course of ophthalmopathy and its response to
      treatment.

PMID- 9532338
TI  - Thyroxine suppression therapy in Graves' disease.
AB  - A recent Japanese report of a novel 'block-and-replace' regime for Graves'
      hyperthyroidism in which thyroxine was continued alone after the combination
      therapy was stopped was associated with a negligible relapse rate of less than
      2%. Such a finding has the potential to revolutionize the management of Graves'
      disease but a similarly large study from Scotland failed to confirm any benefit
      from the new treatment. Apart from obvious differences in race and dietary iodine
      there is no adequate explanation for the discrepant results. In all studies
      reporting a fall in thyrotropin (TSH) receptor antibodies (TRAb) and/or relapse
      rates following conventional or novel 'block-and-replace' regimes, serum TSH
      concentrations were often elevated in the control groups treated with antithyroid
      drugs alone. Theoretically, this could lead to continued expression of thyroid
      cell surface antigen, increased production of TRAb and an adverse effect on
      remission rates. This, however, fails to explain the extraordinary low remission
      rates of the original study from Japan and, in the meantime, there is no good
      reason to adopt the novel regime, at least in Caucasians.

PMID- 9532339
TI  - Prevention and treatment of postpartum Graves' disease.
AB  - Postpartum Graves' disease requires differentiation from postpartum thyroiditis
      and subacute thyroiditis in addition to other causes of hyperthyroidism. This may
      be done by assessing thyrotropin receptor antibody and radioiodine uptake
      together with clinical examination and thyroid scanning. The effect of pregnancy
      on thyroid function causes changes in iodine metabolism, thyroid hormone
      transport proteins and thyroid gland size. Amelioration of autoimmune disease
      such as Graves' disease, systemic lupus erythematosus and rheumatoid arthritis is
      often observed during pregnancy followed by postpartum exacerbation. The
      immunological effects of pregnancy involve placental factors as well as a
      transient diversion from T helper (Th) 1 to Th2 T-cell cytokine profile in
      addition to a change in B-cell lymphopoiesis. Prevention of postpartum Graves'
      disease by immune strategies which have been experimentally performed to reduce
      expression of diabetes in the non-obese diabetic mouse are attractive but not
      currently feasible in humans. Treatment of Graves' disease prior to pregnancy or
      postpartum with 131I is effective. Therapy with anti-thyroid drugs with or
      without thyroxine is variably effective.

PMID- 9532340
TI  - Management guidelines for hyperthyroidism.
AB  - Anti-thyroid drugs, surgery and radioiodine all represent effective forms of
      treatment for Graves' hyperthyroidism. There is, however, little consensus
      regarding the treatment of choice for specific cases. This lack of consensus
      prompted the development of guidelines for good practice in the management of
      hyperthyroidism for the United Kingdom. This chapter describes the process of
      development of this United Kingdom consensus statement, and associated audit
      measures, and highlights outstanding contentious issues in the management of
      Graves' hyperthyroidism.

PMID- 9532341
TI  - Treatment of Graves' disease: the American way.
AB  - The treatment of patients with Graves' disease involves a physician making a
      clinical decision between one of the three modalities available for treatment,
      administering the treatment and following the patients. There appears to be a
      difference in treatment bias for treating the 'average' patient with Graves'
      disease, with American physicians preferring radioactive iodine while their
      European and Japanese cohorts prefer long-term anti-thyroid drugs. There are no
      facts to support this bias. The treating physician usually makes the decision
      based on his or her preference. In addition, American physicians are under
      pressure to prescribe the most cost-effective therapy, leading to an even
      stronger bias towards radioactive iodine.

PMID- 9532342
TI  - Agitation in dementia.

PMID- 9532343
TI  - A protective effect of apolipoprotein E e2 allele on dementia in Down's syndrome.
AB  - BACKGROUND: The apolipoprotein E (ApoE) e4 allele has been associated with an
      increased risk for Alzheimer's disease, whereas the e2 allele has been shown to
      be protective. Similar effects in Down's syndrome (DS) have been postulated but
      not yet demonstrated. METHODS: We obtained DNA from 221 DS individuals and from
      162 population controls, and 77 DS children. Older DS subjects were evaluated for
      dementia and compared to age-matched DS controls. RESULTS: The DS sample with
      dementia (n = 31) had a significantly lower frequency of the ApoE e2 allele
      compared to age-matched nondemented DS controls (0% vs. 8.3%, p = .0136). The
      older DS population had a significantly lower frequency of ApoE e4 compared to
      population controls (11.7% vs. 20.6%, chi-square 8.9, p = .0028). CONCLUSIONS:
      The lower frequency of the e2 allele in demented DS subjects compared to age
      matched nondemented DS controls suggests a protective effect for ApoE e2 in the
      development of dementia in DS. The lower frequency of ApoE e4 in our older DS
      sample compared to population controls points to a detrimental effect of the e4
      allele on longevity.

PMID- 9532344
TI  - Adrenal responsivity in normal aging and mild to moderate Alzheimer's disease.
AB  - BACKGROUND: Enhanced levels of cortisol have been found in moderate to severe
      Alzheimer's disease (AD) and in major depression, while recent studies have
      suggested decreased levels of serum dehydroepiandrosterone sulfate (DHAS) in
      patients with dementia. In this study the responsivity of the adrenal cortex to
      stimulation with a new low dose adrenocorticotropin (ACTH) test was investigated
      in patients with AD and in normal aging. METHODS: Thirteen patients with mild to
      moderate AD, 12 healthy old controls, and 15 young controls (78.0 +/- 8.4, 76.7
      +/- 7.0, and 28.3 +/- 4.1 years old, mean: +/- SD, respectively) received an
      intravenous bolus injection of 1 microgram ACTH. Serum cortisol and androgen
      levels were analyzed before and 5, 10, 20, 25, 30, 35, 40, 60, 90, 120, 180, and
      240 minutes after injection. RESULTS: The cortisol responsivity did not differ
      between the three groups. An enhanced release of androgens was present in
      patients with AD. AD per se had an independent influence on androstenedione
      levels after ACTH stimulation after adjustments for age and gender in a general
      linear regression model. CONCLUSIONS: In contrast to major depression, increased
      cortisol release to ACTH stimulation does not seem to be a feature of AD.
      Abnormal androgen levels after ACTH stimulation are characteristic features of
      mild to moderate Alzheimer's disease.

PMID- 9532346
TI  - Effects of "isolated" transcutaneous electrical nerve stimulation on memory and
      affective behavior in patients with probable Alzheimer's disease.
AB  - BACKGROUND: In previous studies, transcutaneous electrical nerve stimulation
      (TENS), tactile stimulation, and a combination of the two resulted in cognitive
      and affective improvements in patients with Alzheimer's disease (AD). As in those
      studies the therapist was present during the treatment of the experimental and
      control group (sham stimulation), a positive effect of the combination of TENS
      with interpersonal communication could not be excluded. Therefore, the effects of
      "isolated" TENS, i.e., in the absence of the therapist, on memory and affective
      disturbances in AD patients were examined. METHODS: Eighteen subjects (78-92
      years old) met the NINCDS-ADRDA criteria for the clinical diagnosis of probable
      AD. To evaluate treatment effects, the experimental group (9) and the control
      group (9) underwent a number of neuropsychological tests and two observation
      scales. RESULTS: Treatment effects were observed for nonverbal short-term (Visual
      Memory) and long-term (Face Recognition) memory, word fluency (Verbal Fluency),
      and need of help, whereas patients' affective behavior did not improve.
      CONCLUSIONS: The results of the present study show that isolated TENS has a
      positive effect on patients' cognitive and independent functioning; however,
      isolated TENS appeared not to have a therapeutic effect on patients' affective
      behavior.

PMID- 9532345
TI  - The influence of ondansetron and m-chlorophenylpiperazine on scopolamine-induced
      cognitive, behavioral, and physiological responses in young healthy controls.
AB  - BACKGROUND: There is evidence from animal and human experiments that learning and
      memory come under the separate influence of both cholinergic and serotonergic
      pathways. We were interested in learning whether serotonergic drugs could
      attenuate or exacerbate the memory-impairing effects of anticholinergic blockade
      in humans. METHODS: The selective serotonin 5-HT3 receptor antagonist ondansetron
      (0.15 mg/kg i.v.) and the serotonergic agent m-chlorophenylpiperazine (m-CPP;
      0.08 mg/kg i.v.) were administered in combination with the anticholinergic agent
      scopolamine (0.4 mg PO) and compared to scopolamine alone in 10 young, healthy
      volunteers. Testing occurred on three separate days. RESULTS: As expected, i.v.
      administration of scopolamine induced significant impairments in episodic memory
      and processing speed; however, these scopolamine-induced cognitive deficits were
      not attenuated by pretreatment with i.v. ondansetron (0.15 mg/kg), nor were they
      exacerbated by administration of i.v. m-CPP (0.8 mg/kg) in addition to
      scopolamine; however, administration of i.v. m-CPP was followed by a significant
      increase of self-rated functional impairment, altered self-reality, and dysphoria
      ratings, and scopolamine's effect on pupil size was potentiated. CONCLUSIONS:
      Together, these results suggest that in young, healthy volunteers scopolamine
      induced changes of cognitive performance are only minimally modulated by the
      serotonergic effects on ondansetron and m-CPP. Further studies with older
      controls are needed to test whether these findings may be influenced by age.

PMID- 9532347
TI  - Identification of sequence variants and analysis of the role of the catechol-O
      methyl-transferase gene in schizophrenia susceptibility.
AB  - BACKGROUND: Deletions of 1.5-2 MB of chromosome 22q11 have been previously
      associated with schizophrenia. The deleted region includes proximally the region
      harboring genes involved in DiGeorge and velocardiofacial syndromes. Distally, it
      includes the gene for catechol-O-methyl-transferase (COMT), an enzyme that
      catalyzes the O-methylation of catecholamine neurotransmitters, including
      dopamine, and which therefore is considered a candidate gene for schizophrenia.
      METHODS: We address the issue of a direct involvement of the COMT gene in the
      development of schizophrenia by employing the first extensive mutational analysis
      of this gene in a sample of 157 schizophrenia patients and 129 healthy controls,
      using single-strand conformation polymorphism and chemical cleavage
      methodologies. RESULTS: No mutations were found, but several sequence variants
      were identified, including the genetic polymorphism that underlies the high/low
      activity of the enzyme (a Val158-->Met change, which results in the creation of
      an NlaIII restriction site in the low-activity allele). The distribution of the
      NlaIII genotypes among subsets of schizophrenia patients was analyzed.
      CONCLUSIONS: The results presented here argue against a major role of COMT in
      schizophrenia in general (although a minor effect could not be excluded) and
      represent a first step toward a more refined delineation of the
      phenotype/genotype relationship between 22q11 microdeletions and schizophrenia
      susceptibility.

PMID- 9532348
TI  - Twelve-nucleotide repeat polymorphism of D4 dopamine receptor gene in Chinese
      familial schizophrenic patients.
AB  - BACKGROUND: Disturbances in dopaminergic transmission have been implicated in the
      etiology of schizophrenia. Catalano et al reported an association between
      delusional disorder and the number of a 12-nucleotide (bp) repeat sequence in the
      first exon of dopamine D4 receptor gene (DRD4), which indicated a possible role
      of this polymorphism in the pathogenesis of psychotic disorders. METHODS: DNA of
      42 Chinese controls, 50 sporadic schizophrenic patients, and 30 familial
      schizophrenic probands were collected. Genotype of the 12-bp repeat polymorphism
      of DRD4 was determined with polymerase chain reaction and agarose gel
      electrophoresis. Genotypic and allelic frequencies were compared among the three
      groups using the chi-square test. RESULTS: Forty-three (86%) sporadic
      schizophrenic patients, 25 (83.3%) familial schizophrenic probands, and 35
      (83.3%) controls were A1 (two 12-bp repeat) homozygotes. One (2.0%) sporadic
      schizophrenic and 1 familial schizophrenic patient were A2 (one 12-bp repeat)
      homozygotes. There was no significant difference in allelic and genotypic
      distributions among the three groups. CONCLUSIONS: The present data do not
      support an association between schizophrenia and any specific allele of the 12-bp
      repeat polymorphism of DRD4. Significance of familial/sporadic division of
      schizophrenia cannot be supported regarding this repeat polymorphism.

PMID- 9532349
TI  - Reversal of isolation rearing-induced deficits in prepulse inhibition by Seroquel
      and olanzapine.
AB  - BACKGROUND: Prepulse inhibition (PPI) of startle provides an operational measure
      of sensorimotor gating in which a weak stimulus presented prior to a startling
      stimulus reduces the startle response. PPI deficits observed in schizophrenia
      patients can be modeled in rats by individual housing from weaning until
      adulthood. Deficits in PPI produced by isolation rearing can be reversed by
      antipsychotics. METHODS: We evaluated the ability of Seroquel and olanzapine to
      reverse the isolation-induced disruption of PPI. Rats housed for 8 weeks singly
      or in groups of 3 were tested every 2 weeks after either Seroquel (0, 5.0 mg/kg)
      or olanzapine (0, 2.5, 5.0 mg/kg). Startle was elicited by 120-dB pulses
      presented either with or without prepulses (3, 6, or 12 dB above a 65-dB
      background). RESULTS: Isolation rearing repeatedly disrupted PPI and sometimes
      increased startle reactivity. Seroquel reversed these deficits without affecting
      PPI in socially reared controls. Olanzapine (2.5 mg/kg) reversed the isolation
      rearing-induced PPI deficit and tended to increase basal PPI levels. Both
      antipsychotics antagonized the isolation rearing-induced increase in startle
      reactivity. CONCLUSIONS: Isolation rearing produces deficits in sensorimotor
      gating in rats that are reversible by atypical antipsychotics, and may therefore
      aid in identifying new treatments for schizophrenia.

PMID- 9532350
TI  - Whole blood serotonin relates to violence in an epidemiological study.
AB  - BACKGROUND: Clinical and animal studies suggest that brain serotonergic systems
      may regulate aggressive behavior; however, the serotonin/violence hypothesis has
      not been assessed at the epidemiological level. For study of an epidemiological
      sample we examined blood serotonin, because certain physiological and behavioral
      findings suggested that it might serve as an analog marker for serotonergic
      function. METHODS: Whole blood serotonin was measured in a representative birth
      cohort of 781 21-year-old women (47%) and men (53%). Violence was measured using
      cumulative court conviction records and participants' self-reports. Potential
      intervening factors addressed were: gender, age, diurnal variation, diet,
      psychiatric medications, illicit drug history, season of phlebotomy, plasma
      tryptophan, platelet count, body mass, suicide attempts, psychiatric diagnoses,
      alcohol, tobacco, socioeconomic status, IQ, and overall criminal offending.
      RESULTS: Whole blood serotonin related to violence among men but not women.
      Violent men's mean blood serotonin level was 0.48 SD above the male population
      norm and 0.56 SD above the mean of nonviolent men. The finding was specific to
      violence, as opposed to general crime, and it was robust across two different
      methods of measuring violence. Together, the intervening variables accounted for
      25% of the relation between blood serotonin and violence. CONCLUSIONS: To our
      knowledge, this is the first demonstration that an index of serotonergic function
      is related to violence in the general population.

PMID- 9532351
TI  - Circulating lymphocyte phenotypic surface markers in anxiety disorder patients
      and normal volunteers.
AB  - BACKGROUND: Although the relationship between stress and immune function is an
      area of active investigation, there have been few reports studying the
      relationship between anxiety disorders and the immune system. METHODS: This study
      employs flow cytometry to measure circulating lymphocyte phenotypic markers in 20
      medication-free patients with panic disorder, 33 medication-free patients with
      generalized social phobia, and 32 healthy controls. RESULTS: Both patients with
      panic disorder and patients with social phobia had increased CD16 (natural
      killer) cell numbers. Panic disorder patients also had increased numbers of CD19
      cells (B lymphocytes), human leukocyte antigen (HLA)-DR-presenting cells, and
      more cells with the combination of HLA-DR and CD19 surface markers (B lymphocytes
      with HLA-DR on their surface). CONCLUSIONS: These preliminary data suggest that
      subjects with panic disorder may have alterations in circulating lymphocyte
      profiles.

PMID- 9532352
TI  - Sertraline in the treatment of depression associated with gonadotropin-releasing
      hormone agonist therapy.
AB  - BACKGROUND: Endometriosis is thought to affect 5-10% of reproductive age women in
      the general population and is commonly treated with gonadotropin-releasing
      hormone (GnRH) agonists. Recent studies suggest depressive symptoms are
      associated with women treated with GnRH agonist for endometriosis. METHODS: A
      retrospective pilot study of 42 female patients, 22 in the treatment group
      (sertraline) and 20 in the control group (no sertraline), was conducted. All
      subjects had laproscopically diagnosed endometriosis and were treated with 24
      weeks of GnRH agonist therapy. Assessment instruments included the Hamilton
      Depression Rating Scale and the Menopausal Symptom Index. RESULTS: The results
      indicate that patients receiving concomitant sertraline reported significantly
      less depressive symptoms, but did not differ significantly in physical symptoms
      than the group receiving a GnRH agonist alone. CONCLUSIONS: Antidepressants, such
      as sertraline, appear to be significantly helpful in the treatment of mood
      symptoms during the course of GnRH agonist therapy.

PMID- 9532353
TI  - Mazapertine and hyponatremia.

PMID- 9532354
TI  - Cavum septum pellucidum in schizophrenia.

PMID- 9532355
TI  - Cranial electrostimulation therapy.

PMID- 9532356
TI  - [New data on digestion-absorption functions of the small intestine and kidneys of
      newborn].

PMID- 9532357
TI  - [Melatonin and gastric ulcer development during acute emotional stress in rats].

PMID- 9532358
TI  - [The role of salivary glands in removal of noradrenaline excess in blood plasma].

PMID- 9532359
TI  - [Diaphragm blood flow in elevated respiratory resistance].

PMID- 9532360
TI  - [Long-term cardioprotective effect of nitric oxide: the role of HSP70].

PMID- 9532361
TI  - [Possible role of nitric oxide in pathogenesis of model seizure of the different
      etiology].

PMID- 9532362
TI  - [Hypotensive effect and tissue distribution of nitric oxide donor--dinitrosyl
      iron complexes].

PMID- 9532363
TI  - [Postresuscitation restoration of central nervous system functions during
      systemic administration of new peptide analog of pyracetam].

PMID- 9532364
TI  - [Effect of hyperadrenalinemia on the level of adrenaline and noradrenaline in
      tissues of the gastrointestinal system of rats].

PMID- 9532365
TI  - [Changes in resistance of Ca-transporting system of myocardial sarcoplasmic
      reticulum during "urgent"and "long-term" adaptation to physical load].

PMID- 9532367
TI  - [Synthesis of nitric oxide by mouse peritoneal macrophages induced by C-reactive
      protein].

PMID- 9532366
TI  - [Cold induced paralysis of the thermoregulation center and restoration of its
      functions at the paralysis temperature].

PMID- 9532368
TI  - [Effect of digoxin on activity of myocardial acid hydrolases].

PMID- 9532369
TI  - [Comparison of effects of haloperidol and phenamine on acquisition and functional
      disturbance of escape reaction].

PMID- 9532370
TI  - [Anti-arrhythmia properties of the novel combined preparation based on sufan and
      possible mechanism of their realization].

PMID- 9532371
TI  - [Preparation Baliz 2 suppresses evoked activity of hippocampal pyramidal
      neurons].

PMID- 9532372
TI  - [Induction of expression of prolactin receptors in cholangiocytes of male and
      female rats after ligation of the common bile duct].

PMID- 9532373
TI  - [Absence of relation between activity of mono- and polyclonal anti-rhesus
      immunoglobulins in in vitro and in vivo tests].

PMID- 9532374
TI  - [Study of DNA damage of blood mononuclear cells in patients with systemic lupus
      erythematosus by the method of DNA-comets].

PMID- 9532375
TI  - [Effect of glycoforms of alpha1-acid glycoprotein on in vitro production of tumor
      necrosis factor and interleukin-1 by mononuclear leukocytes from human peripheral
      blood].

PMID- 9532376
TI  - [Study of mouse synaptonemal complex after camptothecin administration].

PMID- 9532377
TI  - [Certain biological properties of mutant human tumor necrosis factor-alpha].

PMID- 9532378
TI  - [Treatment of the endometrial adenomatosis with tamoxifen in patients of
      reproductive age].

PMID- 9532379
TI  - [Body thiamine level in acute alcohol psychoses].

PMID- 9532380
TI  - [Calcium response in thyrocytes during changes in the functional condition of the
      thyroid gland].

PMID- 9532381
TI  - [Effect of behavioral activity on recovery processes in resuscitated rats].

PMID- 9532382
TI  - [Various aspects of functional morphology of the extracellular matrix in the
      endothelium of lymphatic capillaries].

PMID- 9532383
TI  - [Re-epithelialization of the skin wound under collagen based dressing].

PMID- 9532384
TI  - [A method of quantitative morphologic analysis of acute local damage and
      myocardial infarction].

PMID- 9532385
TI  - [Amplitude-temporal parameters of the differential rheogram during rat
      desympathization].

PMID- 9532386
TI  - Dolly, cloning, and the public misunderstanding of science: a challenge for us
      all.

PMID- 9532387
TI  - Voices from Roslin: the creators of Dolly discuss science, ethics, and social
      responsibility. Interview by Arlene Judith Klotzko.

PMID- 9532388
TI  - Cloning: then and now.

PMID- 9532389
TI  - Cloning in the popular imagination.

PMID- 9532390
TI  - Power without responsibility: media portrayals of Dolly and science.

PMID- 9532391
TI  - A life in the shadow: one reason why we should not clone humans.

PMID- 9532392
TI  - Cloning and human dignity.

PMID- 9532393
TI  - Cloning, ethics, and religion.

PMID- 9532394
TI  - The regulation of technology.

PMID- 9532395
TI  - Mom, dad, clone: implications for reproductive privacy.

PMID- 9532396
TI  - Ethical aspects of cloning techniques: opinion of the Group of Advisers on the
      Ethical Implications of Biotechnology of the European Commission.

PMID- 9532397
TI  - Ethical aspects of genetic modification of animals: opinion of the Group of
      Advisers on the Ethical Implications of Biotechnology of the European Commission.

PMID- 9532399
TI  - CQ sources/bibliography.

PMID- 9532398
TI  - Little lamb, who made thee? A letter from Edinburgh.

PMID- 9532400
TI  - This porridge is too thin.

PMID- 9532401
TI  - Demolishing a 'straw man'.

PMID- 9532402
TI  - Sperm donation from a comatose, dying man.

PMID- 9532403
TI  - Human cloning: analysis and evaluation.

PMID- 9532404
TI  - Physician-hastened death and end-of-life care: development of a community-wide
      consensus statement and guidelines.

PMID- 9532405
TI  - Cutaneous T-cell lymphoma: a model for selective immunotherapy.

PMID- 9532406
TI  - Use of dexamethasone with 5-HT3-receptor antagonists for chemotherapy-induced
      nausea and vomiting.
AB  - The use of 5-hydroxytryptamine (HT)3-receptor antagonists represents a major
      improvement in the management of chemotherapy-induced nausea and vomiting.
      Despite treatment with a 5-HT3-receptor antagonist, nausea and vomiting persist
      in approximately 40% to 60% of patients receiving highly emetogenic chemotherapy.
      To improve control of acute emetic episodes, dexamethasone is frequently added to
      enhance the antiemetic efficacy of a 5-HT3-receptor antagonist. Combination
      therapy with dexamethasone is rational given the different mechanisms of action,
      low incidence of adverse effects, and potential synergistic effect with 5-HT3
      receptor antagonists. In > 1,600 cisplatin-treated patients evaluated in
      randomized clinical trials, complete response (no nausea and vomiting) was
      achieved in 58% to 92% of patients receiving a corticosteroid plus a 5-HT3
      receptor antagonist, compared with 39% to 79% of patients receiving a 5-HT3
      receptor antagonist alone. Combination antiemetic therapy also has demonstrated
      effectiveness in patients receiving repeat-cycle chemotherapy and in patients
      refractory to other antiemetics, including combinations of traditional
      antiemetics plus corticosteroids or 5-HT3-receptor antagonists alone.
      Intermittent use of high-dose corticosteroids is rarely associated with
      significant adverse effects. A corticosteroid plus a 5-HT3-receptor antagonist is
      a safe and effective combination to control chemotherapy-induced nausea and
      vomiting and should be considered in patients receiving moderately and highly
      emetogenic chemotherapy and in patients refractory to other antiemetics.

PMID- 9532407
TI  - Relapse after successful treatment with immunotherapy: lessons for the future.

PMID- 9532408
TI  - Radiosurgery for metastases from malignant melanoma.

PMID- 9532409
TI  - The blood-brain barrier disruption controversy: does it hold water?

PMID- 9532410
TI  - Patterns of relapse and response to retreatment in patients with metastatic
      melanoma or renal cell carcinoma who responded to interleukin-2-based
      immunotherapy.
AB  - PURPOSE: The purpose of this study was to examine the pattern of relapse and the
      treatment of relapse with either surgery or repeat immunotherapy in patients with
      metastatic melanoma or renal cell carcinoma who had previously responded to
      interleukin-2-based therapy. PATIENTS AND METHODS: Over a 10-year period 1051
      patients with metastatic melanoma or renal cell carcinoma were treated with
      interleukin-2-based immunotherapy at a single institution. One hundred fifty-nine
      patients who relapsed after an initial partial response or complete response to
      interleukin-2-based immunotherapy formed the study population for this
      retrospective review. Medical records, physical examination forms, and relevant
      radiographs were reviewed to determine response, relapse site(s), and response to
      treatment for relapse. RESULTS: Relapse after an initial response to interleukin
      2-based therapy occurred in 84 (80%) of 105 patients with metastatic melanoma and
      in 75 (70%) of 107 patients with metastatic renal cell carcinoma. Relapse after
      an initial partial response involved 71 (97%) of 73 patients with metastatic
      melanoma and 55 (86%) of 64 patients with metastatic renal cell carcinoma. The
      initial site(s) of relapse after a partial response involved a new site(s), old
      site(s), or both old and new sites with relatively even distribution. Relapse
      after an initial complete response occurred in 13 (41%) of 32 patients with
      metastatic melanoma and in 20 (47%) of 43 completely responding patients with
      metastatic renal cell carcinoma. Surprisingly, the initial site of relapse after
      a complete response involved only new sites of disease in 70% of patients.
      Retreatment of relapses with the same interleukin-2-based therapy originally used
      was effective in only one (2%) of 54 selected patients, but a different
      interleukin-2-based therapy in 35 patients resulted in five responders (a 14%
      secondary response rate). Most re-responders, however, responded to treatment
      with tumor-infiltrating lymphocytes and interleukin-2, and only one of 20
      patients responded to retreatment with interleukin-2 alone. Surgical
      metastasectomy with therapeutic intent in 25 selected melanoma patients and in 31
      selected renal cell cancer patients resulted in a 2-year progression-free
      survival of 18% in patients with metastatic melanoma and 37% in patients with
      metastatic renal cell carcinoma. DISCUSSION: In patients with metastatic melanoma
      or renal cell carcinoma, tumor relapse was common after a partial response to an
      interleukin-2-based therapy and included previously identified sites of disease
      in most patients. Relapse after a complete response was less frequent and
      involved only new sites in a majority of patients. In selected patients who
      relapsed, repeat treatment with the same interleukin-2-based therapy that
      provided the initial response was rarely effective. However, with a different
      interleukin-2-based therapy, usually using tumor-infiltrating lymphocytes, repeat
      treatment induced secondary responses in some patients. In addition, salvage
      metastasectomy resulted in durable progression-free survival in selected
      patients.

PMID- 9532411
TI  - In situ radiotherapy with 111In-pentetreotide: initial observations and future
      directions.
AB  - PURPOSE: Somatostatin and its analogues, such as octreotide and lanreotide, are
      used to treat neuroendocrine malignancies. Somatostatin analogues bind to
      somatostatin receptors (sst 1-5), which are differentially expressed in a wide
      variety of neoplasms. Following ligand receptor binding, a fraction of these
      complexes internalize. Internalization of radiolabeled somatostatin analogues,
      especially those that emit Auger electrons, may allow treatment of somatostatin
      receptor-positive tumors by delivering a radioactive isotope to the cancer cell
      in a targeted fashion. 111In-pentetreotide, an sst-2-preferring somatostatin
      analogue, has been used for scintigraphic evaluation and management of
      neuroendocrine cancer patients. We hypothesized that binding and internalization
      of 111In-pentetreotide, an Auger electron emitter, may induce receptor-specific
      cytotoxicity and could be a useful therapeutic agent in somatostatin-receptor
      expressing malignancies. METHODS: To test this hypothesis, subjects who had
      failed conventional therapy and had somatostatin-receptor-positive malignancies,
      as determined by positive uptake on a 6.0 mCi 111In-pentetreotide scan, were
      treated with two monthly 180 mCi intravenous injections of 111In-pentetreotide.
      CT scans were obtained before therapy and within 30 days following the completion
      of the second 111In-pentetreotide dose. Toxicity was evaluated using standard
      criteria. RESULTS: Fourteen patients were studied from February 1997 to August
      1997. Clinical benefit occurred in six of 10 gastroenteropancreatic tumor
      patients. Objective partial radiographic responses occurred in two of 14
      patients, and significant tumor necrosis (defined by changes in Hounsfield units)
      developed in six of the 10 gastroenteropancreatic tumor patients. Possible
      treatment-related toxicity included two patients experiencing grade 3/4
      myelosuppression, and two patients had no measurable toxicity. The most common
      toxicity was grade 1/2 hemoglobin (N = 6). CONCLUSION: One hundred eighty
      millicurie (180-mCi) doses of 111In-pentetreotide are well tolerated and are an
      effective therapy in some subjects with somatostatin receptor-expressing tumors.
      The maximal tolerated dose of 111In-pentetreotide and the optimal dosing
      schedules remain to be determined.

PMID- 9532412
TI  - Gamma knife radiosurgery for malignant melanoma brain metastases.
AB  - PURPOSE: To evaluate the efficacy and toxicity of gamma knife radiosurgery in the
      treatment of melanoma metastases to the brain. PATIENTS AND METHODS: We
      retrospectively reviewed 55 patients with single or multiple intracranial
      melanoma metastases treated at the University of California, San Francisco, with
      gamma knife radiosurgery from 1991 through 1995. Sixteen patients were treated
      with gamma knife radiosurgery for recurrence following previous radiation
      therapy, 11 received radiosurgery as a boost to whole-brain radiation therapy,
      and 28 had radiosurgery alone for initial management of brain metastases. The
      median minimum radiosurgery tumor dose for 140 treated lesions was 19 Gy (range,
      10-22 Gy) prescribed at the 35% to 90% isodose contour (median, 50%). The median
      total target volume per patient was 6.1 cc (range, 0.25-28.3 cc). RESULTS: With a
      median follow-up of 75 weeks in living patients, the median survival times were
      35 weeks overall: 35 weeks for patients with solitary metastases versus 33 weeks
      for those with multiple metastases. A factor that was significant in univariate
      analysis of survival was total target volume treated. This parameter remained
      significant on multivariate analysis. The actuarial median freedom from
      progression analyzed by lesion for 113 lesions in 46 patients with imaging follow
      up was 89 weeks with 6-month and 1-year actuarial freedom from progression rates
      of 89% (95% confidence interval, 80%-95%) and 77% (95% confidence interval, 62%
      87%). In univariate analysis, improved freedom from progression was associated
      with smaller target volume treated, smaller maximum diameter, or higher
      prescribed dose. Four patients (7%) developed acute Radiation Therapy Oncology
      Group grade > or = 2 morbidity, and five patients (9%) developed late grade > or
      = 2 morbidity. DISCUSSION: Median survival and freedom from progression in
      patients treated with radiosurgery for melanoma metastatic to the brain are
      comparable to results in published radiosurgery series of grouped histologies.
      For melanoma patients, total intracranial tumor volume appears to be of greater
      prognostic significance than the absolute number of metastases treated. We
      conclude that gamma knife radiosurgery is effective and should be considered
      among various management strategies.

PMID- 9532414
TI  - Ludwig Robert Muller (1870-1962)--a pioneer of autonomic nervous system research.
AB  - Ludwig Robert Muller, MD, professor of internal medicine, born in 1870 in
      Augsburg, Bavaria, studied medicine from 1890 to 1893 in various European cities
      and specialized in pathology and bacteriology. In 1895, he joined A. Strumpell,
      one of Germany's outstanding internists and neurologists, in Erlangen, Germany.
      Henceforth, Muller focused on the autonomic nervous system. In his 1898
      Habilitation, a thesis required to join the academic faculty, which he entitled
      Anatomy and pathology of the lower spinal cord, he presented studies on the
      autonomic innervation of the bladder and colon. Based on animal studies, he
      continued to publish essential findings on the autonomic innervation of heart,
      lungs, and gastrointestinal tract. Muller was the first to report afferent
      pathways from internal organs to the brain. His book The vegetative nervous
      system was first published in 1920. In 1931, he wrote the book Lebensnerven und
      Lebenstriebe (Life nerves and life instincts). Many of his papers dealt with the
      regulation of thirst, hunger and sleep. He was Chairman of Internal Medicine in
      Wurzburg, Germany, from 1914 to 1920, and also in Erlangen as Strumpell's
      successor from 1920 to 1936. The broad scope of Muller's publications makes him
      one of the important pioneers of autonomic nervous system research.

PMID- 9532413
TI  - The potential for complete and durable response in nonglial primary brain tumors
      in children and young adults with enhanced chemotherapy delivery.
AB  - PURPOSE: Radiographic tumor response and survival were evaluated in the pediatric
      and young adult population with germ cell tumor, primary CNS lymphoma, or
      primitive neuroectodermal tumor receiving intra-arterial carboplatin- or
      methotrexate-based chemotherapy with osmotic blood-brain barrier disruption
      (BBBD). PATIENTS AND METHODS: Thirty-four patients with histologically confirmed
      germ cell tumor (n = 9), primary CNS lymphoma (n = 9), or primitive
      neuroectodermal tumor (n = 16) were treated at the Oregon Health Sciences
      University from August 1981 through April 1995. Ages ranged from 1 to 30 years
      (mean, 18 years). Prior treatments included cranial radiation (n = 10) and
      chemotherapy (n = 18). All patients underwent extensive baseline
      neuropsychological evaluation and follow-up evaluation upon completion of the
      protocol, except for two patients who declined follow-up assessment. RESULTS: Six
      hundred and forty-five BBBD procedures were performed with no mortality.
      Significant complications included one episode of tonsillar herniation with no
      neurologic sequelae, 4% incidence of seizures, and 3% incidence of sepsis or
      granulocytopenic fever. Ototoxicity was seen in 61% of patients who received
      carboplatin chemotherapy. Eighty-two percent of the patients had an objective
      response to treatment, including 62% with complete response and 20% with partial
      response. For most patients, cognitive functioning was maintained or improved at
      follow-up; this pattern was statistically significant. Three of the test scores
      for the seven patients who did not receive radiation therapy showed a cognitive
      decline of at least one standard deviation. Among the nine patients who received
      radiation therapy before or after BBBD chemotherapy, 11 test scores showed a
      decline in cognitive function at one standard deviation or more. DISCUSSION:
      Durable responses were seen in patients with germ cell tumor and primary CNS
      lymphoma when treated with BBBD. Primitive neuroectodermal tumor requires post
      chemotherapy radiotherapy for a durable response to be attained. Ototoxicity was
      a major form of toxicity in the patients who received carboplatin, but with the
      recent introduction of sodium thiosulfate, this problem has been markedly
      alleviated. Favorable cognitive outcomes appeared more likely for patients
      treated solely with BBBD chemotherapy and not with radiotherapy. Trends in the
      results for this sample are similar to those of previous research showing that
      radiotherapy is associated with cognitive decline. Current alternatives to
      enhanced drug delivery after BBBD include bone marrow transplantation; however,
      the increment in drug delivery is less, the number of courses is limited, and the
      morbidity and mortality are greater for bone marrow transplant than for BBBD. The
      current results suggest that in future trials, irradiation may not be needed in
      lymphoma and may not be necessary in some CNS germ cell tumors and that more
      focal radiotherapy should be further assessed in localized primitive
      neuroectodermal tumors.

PMID- 9532415
TI  - Spontaneous blood pressure oscillations and cerebral autoregulation.
AB  - The relationship between spontaneous oscillations in cerebral blood flow velocity
      (CBFV) and arterial blood pressure (ABP) was analysed in normal subjects in order
      to evaluate whether these relationships provide information about cerebral
      autoregulation. CBFV was measured using transcranial Doppler sonography and
      continuous ABP and heart rate using Finapres in 50 volunteers. Measurements were
      made over 5 min in a supine position and 6 min in a tilted position. Coefficients
      of variation were calculated using power- and cross-spectral analysis in order to
      quantify amplitudes within two frequency ranges: 3-9 cycles per min (cpm) (M
      waves); and 9-20 cpm (R-waves). Correlations, coherence values, phase angle
      shifts and gains were also computed between corresponding waves in CBFV and in
      ABP. A clear correlation was seen for M-waves and R-waves between CBFV and ABP
      and coherence values were large enough to calculate phase angle shifts and gains.
      Phase angles for M-waves were larger and gains lower than was the case for R
      waves, either tilted or supine. These data are consistent with a highpass filter
      model of cerebral autoregulation. Relatively high CBFV/ABP gain values (between
      1.4 and 2.0) suggest that the principle of frequency-dependent vascular input
      impedances has to be considered in addition to autoregulatory feedback
      mechanisms. Spontaneous ABP oscillations in the M-wave and R-wave ranges may
      serve as a basis for continuous autoregulation monitoring.

PMID- 9532416
TI  - Assessing microcirculation in familial dysautonomia by laser Doppler flowmeter.
AB  - Microcirculatory vasomotor responses to an alpha-adrenergic agonist and an
      antagonist were assessed in 11 familial dysautonomia and nine control subjects by
      laser Doppler flowmetry. Using two iontophoresis machines, blood flow in the
      midclavicular areas was continuously monitored by two channel laser Doppler
      flowmeter. Simultaneously, the alpha-antagonist (0.5 mM phentolamine
      hydrochloride) and a control solution (0.9% saline) were iontophoresed at 200
      microA for 15 min. The alpha-agonist (0.5 mM norepinephrine bitartrate) was then
      iontophoresed (20 microA) to both pretreated areas for progressively longer
      pulses separated by 3-min observation intervals (15, 30, 60, 90, 120 s). The
      familial dysautonomia subject group had higher mean baseline perfusion with
      widely fluctuating baselines, especially on the phentolamine pretreated side (P =
      0.03). Saline iontophoresis significantly increased perfusion in the control
      group, but not in the familial dysautonomia group (ANOVA: P = 0.02 and 0.15,
      respectively). There was > 100% increase in flow by the end of the saline
      observation period in seven of nine controls, but in only three of 11 familial
      dysautonomia subjects. Phentolamine iontophoresis differentiated familial
      dysautonomia subjects into responders and nonresponders by 7-8 min when all nine
      control subjects, but only five of 11 familial dysautonomia subjects, had > 200%
      increase in blood flow. Irrespective of pretreatment type, norepinephrine
      decreased blood flow in both familial dysautonomia and control groups (ANOVA: P <
      0.0001), but the final mean change after saline was greater in the control group,
      P = 0.02. The final mean changes of flow after phentolamine pretreatment were not
      different between the two groups and were comparable to the familial dysautonomia
      group's smaller response after saline pretreatment. Higher baseline perfusion
      suggests dilation may be intrinsic to familial dysautonomia vasculature. Two
      populations of familial dysautonomia subjects are noted; those who like controls
      increase blood flow with iontophoresis of the alpha-antagonist and those who are
      refractory. In addition, in familial dysautonomia subjects, the microcirculatory
      constrictive response to alpha-agonist iontophoresis is less than that observed
      for controls. These data suggest that some familial dysautonomia subjects may
      have decreased or dysfunctional adrenoceptors as well as decreased innervation.

PMID- 9532417
TI  - Comparison of responses evoked by mild indirect cooling and by sound in the
      forearm vasculature in patients with homozygous sickle cell disease and in normal
      subjects.
AB  - In normal individuals, novel or noxious stimuli commonly evoke the pattern of the
      alerting or defence response which includes cutaneous vasoconstriction, but
      vasodilatation in forearm skeletal muscle. We have compared cardiovascular
      responses evoked by sound and by indirect cooling in 60 patients with homozygous
      sickle cell (SS) disease and in 30 control subjects with normal haemoglobin
      genotype (AA). A sound of 90 dB, 1 kHz for 30s evoked an increase in hand and
      forearm cutaneous vascular resistance (HCVR and FCVR) in SS patients and an
      increase in HCVR in AA subjects, as assessed from Doppler flowmetry. Meanwhile, a
      decrease in forearm vascular resistance (FVR) assessed by venous occlusion
      plethysmography, occurred in 14 out of 30 AA subjects and 25 out of 60 SS
      patients, indicating vasodilatation in forearm muscle; an increase in FVR
      occurred in the remainder. The proportions of SS patients and AA subjects who
      showed an increase in FVR (53% vs 57%) were not significantly different. Cooling
      increased HCVR and FCVR in SS patients and increased FCVR in AA subjects; a
      decrease in FVR indicating vasodilatation, occurred in 12 out of 30 AA subjects,
      but in only 10 out of 60 SS patients. The proportion of SS patients who showed an
      increase in FVR to cooling was greater than in AA subjects (83% vs 60%, P <
      0.05). Thus, SS patients are just as capable of showing the muscle vasodilatation
      of the alerting response to sound as AA subjects. That few SS patients showed
      muscle vasodilatation in response to cooling is consistent with the view that
      reflex vasoconstrictor responses to cooling are particularly strong in SS
      patients. This, in turn, is consistent with our hypothesis that the reflex
      vasoconstrictor response to cooling acts as a trigger for the painful crisis of
      SS disease by diverting blood flow away from active bone marrow.

PMID- 9532418
TI  - In vivo model systems in P-glycoprotein-mediated multidrug resistance.
AB  - In this article we review the in vivo model systems that have been developed for
      studying P-glycoprotein-mediated multidrug resistance (MDR) in the preclinical
      setting. Rodents have two mdr genes, both of which confer the MDR phenotype: mdr
      1a and mdr 1b. At gene level they show strong homology to the human MDR1 gene and
      the tissue distribution of their gene product is very similar to P-glycoprotein
      expression in humans. In vivo studies have shown the physiological roles of P
      glycoprotein, including protection of the organism from damage by xenobiotics.
      Tumors with intrinsic P-glycoprotein expression, induced MDR or transfected with
      an mdr gene, can be used as syngeneic or xenogenic tumor models. Ascites,
      leukemia, and solid MDR tumor models have been developed. Molecular engineering
      has resulted in transgenic mice that express the human MDR1 gene in their bone
      marrow and in knockout mice missing a murine mdr gene. The data on
      pharmacokinetics, efficacy, and toxicity of chemosensitizers of P-glycoprotein in
      vivo are described. Results from studies using monoclonal antibodies directed
      against P-glycoprotein and other miscellaneous approaches for modulation of MDR
      are mentioned. The importance of in vivo studies prior to clinical trials is
      being stressed and potential pitfalls due to differences between species are
      discussed.

PMID- 9532419
TI  - The cellular, immune, and metabolic response to trauma.
AB  - The major challenge in treatment of the multiple trauma victim has shifted from
      early and effective resuscitation to treatment of the host response to injury.
      Patients surviving for the first 24 h after major injury as a result of effective
      resuscitation remain at risk of progressive organ failure and death from what
      appears to be an uncontrolled inflammatory process. A septic cause is frequently
      not identifiable, yet the response is as if the patient were infected. While
      organ-supportive measures such as mechanical ventilation, extracorporeal membrane
      oxygenation, renal replacement therapies, and total parenteral nutrition help to
      maintain tissue substrate delivery and metabolite removal, these therapies
      eventually fail if the microvaculature ceases to function. As the soluble and
      cell-mediated pathways of the inflammatory response are now being unraveled,
      possible interventions designed to attenuate selected elements of the
      inflammatory pathways are being developed. These measures include antioxidants,
      enzyme inhibitors, pharmacological agents, antibodies both to soluble mediators
      and cell surface receptor antagonists. Most of these interventions are at the
      experimental stage and so far have only met with limited clinical success. A
      major problem with attenuation of the inflammatory response is the overlap of
      inflammatory pathways, such that modulation of one or two is unlikely to be of
      benefit in a patient with major injuries. In addition, the speed of these
      responses, once initiated, requires that therapies have to be administered very
      soon after injury to be effective. However, the tremendous increase in knowledge
      of the inflammatory response, and the increasing sophistication of laboratory
      science that can provide both assessment of mediators of inflammation and the
      patients' response to the inflammatory process allows early identification of
      patients at risk of post-trauma organ failure. Armed with this knowledge,
      treatment can be tailored to each patients' individual response to injury, and
      when definitive antiinflammatory regimes are available, patients who can benefit
      from this treatment can be identified rapidly.

PMID- 9532420
TI  - Sonography of testicular tumors and tumor-like conditions: a radiologic
      pathologic correlation.
AB  - Malignant testicular tumors are an important clinical problem, and ultrasound is
      the most frequently ordered imaging modality once a palpable scrotal mass is
      discovered. Numerous articles discussing the role of ultrasound in the evaluation
      of testicular pathology have confirmed the value of preoperative imaging. This
      article presents a review of imaging literature regarding testicular neoplasms,
      with an emphasis on correlation of gross and microscopic tumor pathology and
      imaging findings. Also included are sections on anatomy, epidemiology,
      histogenesis, and tumor markers.

PMID- 9532421
TI  - MR imaging of the foot: anatomy and pathology.
AB  - MR imaging has become a valuable tool in the diagnosis of pathologic conditions
      of the foot. The direct multiplanar imaging capability, superior soft tissue
      contrast discrimination, and spatial resolution afforded by MR are advantages
      over other imaging modalities. The complex anatomy and spectrum of pathology in
      this region present a significant challenge to the radiologist. Familiarity with
      the anatomy, various clinical conditions, and their appearance on MR imaging is
      essential for accurate diagnosis. In this article, a limited review of the
      anatomy of the foot is presented together with a more in-depth discussion and
      illustration of a wide variety of pathologic conditions of the foot. Emphasis is
      placed on those conditions that are relatively unique to the foot.

PMID- 9532422
TI  - Ovine luteinizing hormone heterogeneity: androgens increase the percentage of
      less basic isohormones.
AB  - The heterogeneity of luteinizing (LH) is hormonally regulated with androgens
      having been reported to increase the percentage of extremely basic LH isohormones
      in the ovine pituitary. This study re-examined the effects of androgens on the
      heterogeneity of LH in the ovine pituitary because the extremely basic isoforms
      of LH reported previously were subsequently demonstrated to be artifacts
      resulting from the conditions used for chromatofocusing. Pituitary extracts from
      wethers, rams, and dihydrotestosterone (DHT)-implanted wethers were desalted by
      flow dialysis and chromatofocused on pH 10.5 to 7.0 gradients. LH was quantitated
      by radioimmunoassays. When compared with rams, wethers had increased percentages
      of LH isoforms eluting between pH 9.6 and 10. Patterns of intrapituitary LH
      isohormones were comparable in rams and DHT-implanted wethers except that rams
      had a higher percentage of LH eluting at pH 9.2 (20.9 +/- 2.1% vs. 13.3 +/-
      1.3%). In contrast to what was previously reported, rams and DHT-implanted
      wethers had higher percentages of ovine LH isoforms eluting at pH's 9.4 or lower.
      Thus, androgens alter LH heterogeneity yielding increased percentages of
      isohormones eluting at pH's of 9.4 or lower.

PMID- 9532423
TI  - Progestin-induced growth hormone (GH) production in the treatment of dogs with
      congenital GH deficiency.
AB  - The recent demonstration of the ability of progestins to induce the expression of
      the growth hormone (GH) gene in the mammary gland of dogs and cats opens
      possibilities for the treatment of some forms of GH deficiency with progestins.
      Therefore, one male and one female German shepherd dog with congenital dwarfism
      because of a pituitary anomaly were treated with subcutaneous injections of
      medroxyprogesterone acetate (MPA) in doses of 2.5-5.0 mg per kg body weight,
      initially at 3-wk intervals and subsequently at 6-wk intervals. In both dogs,
      body sizes increased and a complete adult hair coat developed. Undesirable side
      effects were recurrent periods of pruritic pyoderma in both dogs and cystic
      endometrial hyperplasia with mucometra in the female dog. Parallel with the
      physical improvements, plasma insulin-like growth factor I concentrations rose
      sharply. Plasma GH concentrations tended to rise, but never exceeded the upper
      limit of the reference range. Nevertheless, one of the dogs developed slight
      acromegalic features, possibly because mammary GH, unlike pituitary GH, is
      released evenly throughout the day. Even moderate increases in circulating GH
      concentration may, therefore, give rise to overexposure. It is concluded that
      long-term treatment with MPA can be used as an alternative for heterologous GH in
      the treatment of congenital GH deficiency in the dog.

PMID- 9532424
TI  - LH receptor mRNA and cytochrome P450 side-chain cleavage expression in bovine
      theca and granulosa cells luteinized by LH or forskolin.
AB  - This study was undertaken to characterize the cDNA sequence encoding bovine LH
      receptor (LHR), and study the effect of different luteinization protocols on the
      steroidogenic capacity and LHR mRNA in bovine luteal cells. The bovine LHR cDNA
      sequence reported here showed high sequence identity with that of other species.
      Several mRNA splice variants were expressed in bovine corpus luteum (CL). Reverse
      transcription-polymerase chain reaction conducted with primers spanning exons 2
      11 revealed, in addition to the full-length sequence, a shorter fragment
      homologous to splice variant B reported in porcine and ovine LHR cDNA sequences.
      Granulosa and theca cells derived from bovine preovulatory follicles were
      cultured with either forskolin (10 microM, for 8 d culture-Protocol 1) or LH (100
      ng/ml, for 12 hr followed by a 7.5-d culture with 2 ng/ml-Protocol 2). LHR mRNA
      was not detected in luteal granulosa cells (LG); in contrast, luteal theca cells
      (LT) contained LHR mRNA at similar levels when cultured under Protocol 1 or 2.
      cAMP responses to a short challenge with LH were in good agreement with LHR mRNA
      levels. Cytochrome P450 side-chain-cleavage (P450scc) contents were lower in
      luteal cells cultured with LH as compared with cells cultured with forskolin;
      however, the difference between the two luteinization protocols was much larger
      in LT (P < 0.05) than in LG. This study suggests that a) LHR mRNA is mainly
      present in the theca-derived luteal cell and b) LHR mRNA and cytochrome P450scc
      expression in each of the luteal cell types seems to be under different control.

PMID- 9532425
TI  - In ovo treatment with an aromatase inhibitor masculinizes postnatal hormone
      levels, abdominal fat pad content, and GH pulsatility in broiler chickens.
AB  - Vorozole, a selective aromatase inhibitor, was administered in ovo to test the
      specific embryonic role of estrogen in conferring the sex distinction in GH
      release and body phenotype in broilers. On Day 6 of incubation, eggs were
      injected with saline or with different concentrations of vorozole. Postnatal
      blood samples were analyzed for T3, T4, GH, estradiol (E2), and testosterone (T).
      At the age of 4 wk, control and vorozole-treated birds were cannulated, and
      serial blood samples were withdrawn every 10 min for 5 hr, wherein GH pulsatility
      characteristics were determined using deconvolution analysis. The proportional
      abdominal fat pad weight was reduced significantly in the treated groups,
      especially in female birds. The vorozole treatment increased plasma T3, E2, T,
      and GH concentrations, and decreased T4. The frequency of the GH pulses was lower
      and the interval between the bursts (min) was higher in the vorozole-treated
      group, as were the mass secreted per burst (ng/ml), the amplitude (ng/ml/min) and
      the production rate (ng/ml/5 hr). In conclusion, early in ovo treatment with a
      potent aromatase inhibitor is able to increase the mean serum T3 and GH
      concentration and masculinize the GH pulse pattern, resulting in an economically
      favorable decrease in abdominal fat pad content in male and female broilers at
      slaughter age.

PMID- 9532427
TI  - Fatigue of the knee extensor muscles following eccentric exercise.
AB  - The purposes of this study were to determine the time course of muscle fatigue in
      the knee extensor muscles following an eccentric exercise protocol, and to
      determine if the position of the subjects during assessment affected the
      measurement of muscle fatigue. Twenty-four female subjects were assigned to three
      groups. All subjects completed baseline measure (pre-exercise test) of a power
      spectrum analysis of the vastus medialis, rectus femoris and vastus lateralis
      muscles. Following an exercise protocol of 300 eccentric repetitions of the knee
      extensors, power spectrum analysis was repeated at two, four, 20, 24, 48 and 72
      hours for group one, at 0 hour (immediately following the exercise) and two hours
      for group two, and at 0 hour for group three. Groups one and two were tested in
      sitting, while group three was tested supine. The slope of the median frequency
      of the vastus lateralis muscle changed significantly over time (p < 0.001) for
      group one, but there were no significant changes in the slope of the median
      frequency of the vastus medialis muscle, while the rectus femoris muscle showed
      an increase in the slope of the median frequency when the subjects were in the
      sitting position. Further testing, in supine (group three), indicated that the
      position of the hip joint influenced the power spectrum analysis of the rectus
      femoris muscle but not the vasti muscles. In addition, fatigue occurred
      immediately post-exercise with recovery within 24 hours.

PMID- 9532426
TI  - Effects of age, season, and fertility status on plasma and intratesticular
      immunoreactive (IR) inhibin concentrations in stallions.
AB  - The nature of the relationship between inhibin and reproductive function in the
      stallion is yet to be elucidated. Blood and testes from 51 light horse stallions
      ranging in age from 2 mo to 25 years were collected during the breeding and
      nonbreeding seasons to study the effects of testicular maturation, aging, season,
      and fertility status on peripheral and intratesticular concentrations of Ir
      inhibin and other reproductive hormones. Of the 51 stallions, 12 age-matched
      stallions (6 fertile, 3 subfertile, and 3 infertile) were used in the fertility
      study. Blood samples were taken before castration and plasma stored at -20
      degrees C for analysis of Ir inhibin, luteinizing hormone (LH), follicle
      stimulating hormone (FSH), testosterone (T), estradiol (E2), and estrogen
      conjugates (EC) by radioimmunoassay (RIA). Testes were homogenized and testicular
      extracts prepared and frozen at -70 degrees C for analysis of Ir inhibin, T, E2,
      and EC by RIA. Plasma concentrations of Ir inhibin, LH, FSH, T, E2, and EC and
      intratesticular concentrations of Ir inhibin, T, E2, and EC increased with age (P
      < 0.01). The most dramatic effect appeared to be during testicular maturation. An
      aging effect was not observed in adult stallions. A seasonal effect was not
      detected for any of the plasma hormones, whereas for the intratesticular hormones
      the only change noted was an increase in T in the nonbreeding season (P < 0.05).
      Plasma Ir inhibin, E2, and EC were lower (P < 0.01) and gonadotropins higher (P <
      0.05) in infertile stallions. Plasma T levels did not change. Intratesticular Ir
      inhibin concentrations tended to be lower (P < 0.1) in subfertile stallions and
      significantly lower (P < 0.01) in infertile stallions, whereas intratesticular
      steroid levels were not different among the three groups. In conclusion, plasma
      and intratesticular Ir inhibin concentrations seem to be affected by testicular
      maturation and fertility status.

PMID- 9532428
TI  - The masseteric inhibitory reflex in the diagnosis of multiple sclerosis.
AB  - In order to evaluate the reliability of the masseteric inhibitory reflex (MIR) as
      a screening method in the diagnosis of multiple sclerosis (MS), a series of 41
      consecutive patients affected by clinically defined, long-duration forms (mean
      duration 10.9 years) of the disease was examined. In all cases magnetic resonance
      imaging and CSF isoelectrofocusing confirmed the diagnosis. Sensitivity of MIR,
      Blink Reflex and BAEPs were compared. Statistical analysis of data suggested the
      following considerations: 1) a significant concordance was found between MIR and
      the other neurophysiological tests performed (MIR vs. BAEPs in 78.4% of cases, p
      < 0.001; MIR vs. blink reflex in 68.3%, p < 0.02). 2) The S1 early component of
      MIR is a more reliable indicator than S2 late component. 3) In detecting
      brainstem lesions the sensitivity of MIR equaled that of the other
      neurophysiological tests. 4) Poor localizing concordance between
      neurophysiological tests and neuroimaging was found in our series. A possible
      utilization of MIR, as a part of a multimodal neurophysiological approach, even
      in patients affected by possible or probable MS is suggested.

PMID- 9532429
TI  - The effect of Jendrassik manoeuvre on the latency, amplitude and left-right
      asymmetry of tendon reflexes.
AB  - In order to determine the effect of the Jendrassik manoeuvre (JM) on the latency
      and amplitude of the electrically recorded compound action potentials of the
      tendon reflexes (TR) as well as on their left-right asymmetry, the above
      parameters of the knee (KR) and Achilles (AR) TR were measured in 52 normal
      subjects (32 men and 18 women) aged 18-74 years (33 +/- 12.2) both at rest and
      during the JM, using a commercially available tendon hammer connected with the
      electromyograph. The left-right difference of the latencies was not statistically
      significant under both conditions. The knee reflex latency--on both sides--was
      shortened during the JM, while that of the Achilles tendon reflex was not
      significantly altered. The difference of the TR amplitude between the two sides
      in percentage of the lower value was not significant at rest and showed a marked
      diminution during JM. The manoeuvre caused also a net increase of the absolute
      values of the compound action potentials amplitude of both reflexes.

PMID- 9532430
TI  - A field method for blink reflex latency R-1 (BRL R-1) and prediction equations
      for adults and children.
AB  - PURPOSE: To develop a field worthy apparatus for blink reflex latency R-1 (BRL R
      1), to compare mechanical and electrical stimulation, to define a standardized
      measurement of BRL R-1, to test a field worthy procedure and to produce
      population-based prediction equations. METHODS: A special low voltage
      electromyographic (EMG) recording system was constructed which is uninfluenced by
      electrical and magnetic field. The supraorbital notches were stimulated
      mechanically using a small hammer and electrically using a stimulus of 2.0 ms
      duration and 2-5 mA 13. A computer program was developed which substracts the
      baseline for all data points and sums R-1 for 10 tests by identifying the noise
      floor or baseline of the EMG recording and the noise envelope. The beginning of R
      1 and R-2 is defined as 2 times the noise amplitude of this envelope. BRL R-1 was
      compared after tap and after electrical stimulation in 16 subjects. Prediction
      equations were developed from data of 240 adults and 163 children unexposed to
      chemicals. RESULTS: Mechanically and electrically elicited mean BRL R-1 in 16
      subjects was identical at 12.6 ms on the right and 12.7 ms vs 12.5 on the left.
      In adults, BRL R-1 depended on age. In children BRL R-1 was age, weight and
      height dependent. CONCLUSION: BRL R-1 elicited by supraorbital tap is field
      worthy, computer defined and identical to electrical BRL.

PMID- 9532431
TI  - Diagnostic significance of MEP elicited by electrical and magnetoelectric
      stimulation in acute/subacute supratentorial lesions.
AB  - Motor evoked potentials (MEP) elicited by transcranial electrical and
      magnetoelectric stimulation were examined prospectively in a total of 122
      patients with supratentorial tumorous and nontumorous lesions in an
      acute/subacute neurosurgical setting. All patients had a hemiparesis
      contralateral to the lesion. It was the aim of our study to define the diagnostic
      significance of MEP with respect to superficial and deep localization of the
      lesions. To achieve this goal, MEP findings were correlated with the clinical
      motor status defining two categories: correct with pathological MEP, and false
      negative with normal MEP. On the whole, we found correct results in 108 of 122
      patients (88.5%) with electrical stimulation, and in 67 of 75 patients (89.3%)
      with magnetoelectric stimulation. There were false-negative results in 4 (11.5%)
      and 8 (10.7%) cases, respectively. In particular, with electrical stimulation 14
      of 65 (21.5%), and with magnetoelectric stimulation 8 of 43 (18.6%) superficial
      lesions were missed, whereas deep lesions were correctly assessed in every case
      by either stimulation technique. In conclusion, the diagnostic significance of
      MEP for assessment of superficial supratentorial lesions is limited with the
      methods applied in this study. Whether more refined techniques may provide
      different results in a similar setting remains to be proved.

PMID- 9532432
TI  - A comparative study of Japanese and herpes simplex encephalitides.
AB  - The difference in the clinical, electrophysiological and radiological features in
      12 patients with Japanese encephalitis (JE) and eight patients with herpes
      simplex encephalitis (HSE) have been reported in this study. Meningeal signs,
      seizures and behavioural abnormalities in HSE; and decerebration or decortication
      and focal neurologic signs in JE were common. Electroencephalogram in JE revealed
      diffuse delta slowing in 11, whereas in HSE frontotemporal slowing was present in
      five, periodic lateralising epileptiform discharges in three and focal spikes in
      two patients. Magnetic resonance imaging in JE patients revealed characteristic
      bilateral thalamic hyperintense lesions in T2 in all the patients. In HSE, CT
      scan revealed frontotemporal hypodensity in six patients. MRI was more sensitive
      than CT scan. It revealed characteristic frontotemporal hyperintense signals in
      T2 even in two patients who had normal CT scan. Motor evoked potentials were
      abnormal in eight out of nine JE patients, whereas these were normal in all five
      HSE patients in whom these studies were carried out. Attention to these clinical,
      radiological and neurophysiological findings may help in differentiating these
      encephalitides even before the results of serological studies are available.

PMID- 9532433
TI  - Amplitudes of sural and radial sensory nerve action potentials in orthodromic and
      antidromic studies in children.
AB  - Several previous studies of adults have reported that the amplitudes of the sural
      and superficial radial nerve action potentials (SN and SRN SNAP respectively) are
      larger with antidromic than with orthodromic recordings. However, this difference
      has not been documented in children. This study evaluated the amplitudes of SN
      and SRN SNAPs obtained with antidromic and orthodromic recordings in children
      with and without neuropathy and compared these data with findings in adults. The
      SN or SRN or both of 10 neurologically normal children, 6 children with
      neuropathy and 7 healthy adults were studied with surface stimulation and
      recording. The position of the stimulating and recording electrodes for the
      orthodromic recordings was the reverse of that for the antidromic recordings.
      Peak-to-peak SNAP amplitudes were measured and analyzed. The mean of the SRN SNAP
      amplitude was significantly higher with the antidromic than the orthodromic
      technique for the first and third groups (p < 0.05). The mean SN SNAP amplitude
      was higher in the three groups, but not statistically significant when the data
      for the children and adult normal groups were combined and reanalyzed (p < 0.05).
      Consistent responses were obtained with both techniques. However, the antidromic
      technique was superior to the orthodromic technique because of the greater
      amplitude of responses. We recommend the use of the antidromic technique because
      of its greater amplitudes, ease of use and potential reduction of discomfort to
      the patient.

PMID- 9532434
TI  - Muscle fibre orientation of abdominal muscles and suggested surface EMG electrode
      positions.
AB  - The ability of surface electrodes to accurately detect the activity of a
      particular muscle relies not only on their being placed over the muscle but also
      on their position in relation to muscle fibre orientation. For optimal pick-up of
      electromyographic (EMG) signals, surface electrodes are best aligned in parallel
      with the fibre orientation of the underlying muscle. This study aimed to measure
      muscle fibre orientation and other parameters of muscle morphology of the
      abdominal muscles in relation to palpable bony landmarks. Thirty-seven embalmed
      cadavers (19 males and 18 females) were examined. Results showed that the fibres
      of obliquus externus abdominis were about 4 degrees more vertical than the lower
      edge of the eighth rib. Below the rib cage, the muscle fibres of obliquus
      externus abdominis were approximately 5 degrees closer to vertical than a
      reference line between the most inferior point of the costal margin and the
      contralateral pubic tubercle. In the anterolateral abdominal wall area below the
      anterior superior iliac spine (ASIS), the obliquus internus abdominis was
      superficial being covered only by the aponeurosis of obliquus externus abdominis.
      At the level of ASIS, the muscle fibres of obliquus internus abdominis were
      almost horizontally orientated but at 2 cm below ASIS were aligned about 6
      degrees inferomedially to the horizontal. The muscle fibres of upper rectus
      abdominis were 2 degrees inferolateral to the midline while the lower rectus
      abdominis muscle fibres deviated inferomedially from the midline by about 8
      degrees. The appropriate surface electrode placements which follows the muscle
      fibre orientation of the obliquus externus abdominis, obliquus internus abdominis
      and rectus abdominis have been suggested.

PMID- 9532435
TI  - Differential effects of unilateral magnetic cortical stimulation on reaction
      time.
AB  - Data from patients with brain lesions suggested that the right hemisphere is
      involved in the intention of simple movements, while the left is involved in more
      complex tasks. The contributions of each hemisphere to a reaction time (RT) task
      were assessed with cortical magnetic stimulation in five healthy right-handed
      subjects. Subjects were asked to push buttons with both hands as fast as possible
      after a visual start stimulus. At three different delays (25, 50 and 75 ms) after
      the start signal, a magnetic stimulus of 20, 40 or 60% of maximum intensity was
      given to either the right or the left hemisphere. Delay, intensity and side of
      stimulation varied in random order. Repeated measures analysis of variance showed
      two main effects: firstly, RT was longer on the body side innervated by the
      stimulated than by the non-stimulated hemisphere. Thus, cortical stimulation
      delayed the execution of a motor task, as shown previously. Secondly, there was
      an interaction between side of stimulation and delay of the cortical stimulus. At
      a delay of 25 ms, right-sided stimulation resulted in longer RTs than left-sided
      stimulation. At delays of 50 and 75 ms, the reverse proved true. In both cases
      the effect held for both hands. According to these results, the right hemisphere
      is predominantly involved in the early phases of an RT task, while the left
      hemisphere is more involved in later phases of processing. The results show that
      cortical magnetic stimulation can be used to investigate differential
      contributions of the hemispheres to motor tasks in vivo.

PMID- 9532436
TI  - The Morehouse Faculty Development Program: methods and 3-year outcomes.
AB  - BACKGROUND AND OBJECTIVES: Faculty development is an established method for
      increasing the number and effectiveness of faculty in family medicine. However,
      few published studies focus specifically on the use of faculty development to
      increase minority representation among faculty. Underrepresented minorities
      comprise 20% of the nation's population but only 3% of medical school faculty. In
      the entire nation, only 52 full-time teachers of family medicine are African
      Americans. Morehouse School of Medicine has developed an effective model for
      training large numbers of underrepresented minority physicians to become academic
      family physicians. From 1993-1996, we trained 23 community-based physicians,
      three new faculty, six existing faculty, and three full-time fellows as teachers
      of family medicine. Of 35 participants, 33 were underrepresented minorities.
      Cultural issues in teaching and communication are an integral part of the
      curriculum. Seventy-three percent of graduates now teach medical students or
      residents either full-time or part-time. Further studies are needed to test the
      replicability of this model in non-minority institutions, as well as to achieve
      greater cost-effectiveness and improve academic outcomes such as publications and
      research. Significant faculty diversity is necessary and achievable, if
      institutions are willing to commit significant resources and network with
      minority health professionals and institutions.

PMID- 9532437
TI  - Training family medicine faculty to teach in underserved settings.
AB  - BACKGROUND AND OBJECTIVES: Because minority physicians are more likely to
      practice in minority or medically underserved communities, meeting the health
      care needs of underserved populations requires that programs not only train such
      physicians but train minority faculty to act as teachers and role models. The
      Faculty Development Center in Family Medicine at Cook County Hospital has had
      more than 120 graduates, most of whom are teaching and practicing in underserved
      settings. Nearly half have been minorities, the result of the priority given to
      recruitment of minority fellows. The curriculum is specifically geared to prepare
      faculty to work in underserved settings and nurture future physicians for these
      settings. Workforce diversity can be achieved only by major changes in the
      institutional culture of medical education, which federal policy can encourage by
      setting high standards for grant funding preferences and supporting centers of
      excellence for training minority physicians and faculty.

PMID- 9532438
TI  - Knowledge and care of chronic illness in three ethnic minority groups.
AB  - BACKGROUND AND OBJECTIVES: Despite advances in medical approaches to the
      management of chronic illnesses, relatively little is known about how older
      members of ethnic minority groups view their chronic illnesses or how they manage
      them in daily life. METHODS: We recruited 35 African-Americans, 61 Latinos, and
      55 Filipino-Americans, all over age 50. Criteria for entry into the study was the
      presence of one or more chronic illnesses. Findings are based on structured and
      semi-structured questions in one in-depth interview. Qualitative data on
      transcribed interviews with 151 respondents was analyzed. RESULTS: Comparison of
      the three groups revealed social and cultural differences and similarities that
      affected the management of chronic illness. The extent to which respondents
      demonstrated an understanding of their illnesses as chronic varied considerably,
      with discernible differences among groups about knowledge of illness and self
      care practices. CONCLUSIONS: Our findings showed that although major chronic
      illnesses were, for the most part, the same for all three groups, each group
      differed in its response to and management of its illnesses. These findings have
      implications for the education of physicians in training.

PMID- 9532439
TI  - Hmong/medicine interactions: improving cross-cultural health care.
AB  - BACKGROUND AND OBJECTIVES: There are now more than 100,000 Hmong (Southeast
      Asian) refugees in the United States. This study examined interactions between
      Hmong patients and their health care providers and identified specific factors
      that either enable or obstruct health care delivery. METHODS: We used
      semistructured interview techniques to investigate patients' and providers'
      experiences, looking for attitudes, ideas, or behaviors that could be modified to
      improve health care delivery. Interviews with 23 Hmong patients, 18 health care
      providers, and six translators were audiotaped, transcribed, and analyzed by a
      multidisciplinary team. Methods included text analysis, theme identification,
      rank ordering, participant observation, immersion-crystallization, and open-ended
      discussion. RESULTS: Hmong patients and their US-trained health care providers
      have different health belief systems. Both linguistic and cultural translation
      were seen as problematic. Additionally, an overwhelming number of patients
      identified kindness, caring, and a positive attitude as important provider
      characteristics. Providers noted difficulties in understanding Hmong conceptions
      of acute versus chronic diseases, illness prevention, and pain, both physical and
      psychological. Many respondents gave suggestions for improvement: 1) learn more
      about each other's cultures, 2) be patient, kind, and positive, 3) avoid negative
      statements or predictions, 4) improve translation quality, 5) explain medical
      terms using visual aids, 6) respect Hmong family-centered decision making, 7)
      increase the time allotted for translated clinical encounters, and 8) train Hmong
      health care providers. CONCLUSIONS: Many basic issues in relations between
      clinicians and Hmong patients must be addressed to improve health care
      communication.

PMID- 9532440
TI  - Sudanese refugees in a Minnesota family practice clinic.
AB  - BACKGROUND AND OBJECTIVES: During the 1990s, African refugees from the southern
      Sudan were resettled in Minnesota. This research characterizes the health care
      utilization of a small sample of these recently arrived refugees and describes
      their health histories. METHODS: Data were abstracted from the medical charts of
      all identified Sudanese patients in an urban, Midwestern family practice
      residency unit. RESULTS: A small sample of Sudanese refugees were found to have
      high rates of prior infectious illness and experienced communication difficulties
      in accessing health care. CONCLUSIONS: Information about this sample's
      demographic variables, health behavior, health histories, and communication
      difficulties are documented. Some descriptors of the Nuer ethnic group are
      provided, and issues are raised that may help health care workers provide more
      culturally competent care to this Sudanese refugee population.

PMID- 9532441
TI  - Health status of American Indians/Alaska Natives: general patterns of mortality.
AB  - BACKGROUND AND OBJECTIVES: Investigations of American Indian and Alaska Native
      (AI/AN) populations suggest patterns of mortality that differ from the general
      population. Mortality data reveal excess overall mortality among AI/ANs, as well
      as excesses for specific causes of death, including accidents, diabetes, liver
      disease, pneumonia/influenza, suicide, homicide, and tuberculosis. A relative
      deficit of deaths has been noted for heart disease, cancer, and HIV infections.
      It is important that physicians demonstrate cultural competence so they may
      provide quality medical care for the populations they serve. Activities such as
      provider education, risk assessment, and emphasis on preventive services are
      offered to facilitate integration into teaching curricula. Knowledge of
      distinctive mortality patterns among AI/ANs will help clinicians recognize the
      unique needs of these patients.

PMID- 9532443
TI  - Filling the gap: equity and access to oral health services for minorities and the
      underserved.
AB  - BACKGROUND AND OBJECTIVES: Family physicians and other primary care providers
      play a pivotal role in preventing oral disease, especially among minority and
      underserved populations who have limited access to dental services and poorer
      oral health status. Oral diseases/conditions, such as caries, baby bottle tooth
      decay, gingivitis, periodontitis, oral pharyngeal malignancies, and orofacial
      trauma, are prevalent and costly, yet largely preventable. Given their role in
      promoting and protecting overall health and their historical role in serving
      minority and underserved families, family physicians occupy a unique position to
      assure equity, access, and improvement in oral health for all Americans.

PMID- 9532442
TI  - Barriers to health care access for Latino children: a review.
AB  - BACKGROUND AND OBJECTIVES: More than 9 million Latino children currently live in
      the United States. Latinos will soon be the largest minority group in the
      country, but little is known about access barriers to health care faced by Latino
      children. We reviewed the literature to define specific barriers to care for
      Latino children, identify methodologic problems, and highlight the clinical and
      research implications of the identified barriers. METHODS: We did a MEDLINE
      search, using combinations of the key words Hispanic, children, and access. Study
      exclusion criteria included "not an original research article," "enrolled only
      adult subjects," "no separate data analysis for children," and "dental care
      focus." RESULTS: The search yielded 497 citations, of which 27 met the inclusion
      criteria. Of the 32 potential barriers identified, 21 had good supportive
      evidence. Lack of health insurance was a consistent barrier; recent data revealed
      that 26% of Latino children are uninsured, compared with 10% of white children
      and 14% of African-American children. Latino children also are at greater risk
      for episodic insurance coverage, low rates of private insurance, and loss of
      employee-based coverage. Parent beliefs about the etiology and treatment of their
      child's illness, use of home remedies, choice of sources of advice, and folk
      medicine practices may also influence how health care is obtained. Few data are
      available on differences in access among major Latino subpopulations, and no
      studies focused primarily on barriers as perceived by Latino parents. Evidence is
      equivocal or lacking that the following are barriers for Latino children:
      immigration status, duration of parent residency in the United States, and
      acculturation. Several barriers were identified that originate with practices and
      behaviors of health care providers, including reduced screening, missed
      vaccination opportunities, decreased likelihood of receiving prescriptions, and
      poor communication. CONCLUSIONS: Lack of health insurance and lack of a regular
      source of care are major access barriers for Latino children, but many other
      barriers were identified that also can have a substantial effect on health care.
      In addition, the behaviors and practices of both health care providers and
      parents can affect access to care. Too little is known about what parents
      perceive to be the major barriers, access differences among Latino
      subpopulations, the roles of language and culture, and the causes of obstacles
      resulting from the actions of providers.

PMID- 9532444
TI  - Panic disorder in Hispanic patients.
AB  - BACKGROUND AND OBJECTIVES: This study determined the proportion of community
      dwelling Hispanics who present for medical care for their panic attacks and
      identified factors associated with seeking care. We also compared characteristics
      of Hispanic subjects with those of non-Hispanic white panic sufferers. METHODS:
      In this community-based study, subjects with panic attacks completed a structured
      interview concerning health care utilization, panic characteristics, coexisting
      psychiatric problems, and illness attitudes. Hispanics were self-identified and
      completed the Cuellar acculturation scale for Mexican-Americans. RESULTS: Twenty
      nine (53.7%) of 54 Hispanic subjects had sought medical care for their panic
      attacks. Care seeking in non-Hispanic whites was not dependent on these factors.
      CONCLUSIONS: Half of the Hispanics with panic attacks seek no medical care for
      their attacks. Predictors of seeking care among Hispanics in San Antonio included
      coping style, symptom perceptions, and access to transportation.

PMID- 9532445
TI  - Patient ethnicity and diagnosis of emotional disorders in women.
AB  - BACKGROUND AND OBJECTIVES: Ethnic background and family resources have not been
      sufficiently examined in relation to emotional disorders and their treatment in
      primary care settings. This study examined the diagnosis and management of
      psychological disorders in family practice patients to explore how ethnicity may
      affect the diagnosis and treatment of emotional disorders. METHODS: A random
      sample of family practice patients was selected from 1 year of office visits. The
      charts of 100 African-American and 100 Caucasian women were audited for primary
      and secondary diagnoses, presenting symptoms, prescriptions, psychotherapy
      referrals, history of domestic violence and substance use, and family and
      demographic characteristics. Chi-square tests of association and multiple
      regression were used to analyze the data. RESULTS: Ethnic background was
      significantly associated with a diagnosis of a psychiatric disorder; 44% of
      Caucasian patients were diagnosed with an emotional disorder, compared with 24%
      of African-Americans. Proportionately more Caucasian patients with psychiatric
      diagnoses were treated with psychotropic medications. Patient race, marital
      status, and insurance status explained 15% of the variance in psychiatric
      diagnoses. CONCLUSIONS: Women's ethnicity is significantly associated with the
      diagnosis of emotional disorders and their treatment.

PMID- 9532446
TI  - Supplemental fitness activities and fitness in urban elementary school
      classrooms.
AB  - BACKGROUND: The physical activity levels of US children are declining.
      Opportunities for physical activity within city schools are constrained by time
      and space limits. This study determined whether a supplemental program of
      physical activity would significantly alter the fitness levels of low-income,
      minority, urban elementary schoolchildren. METHODS: Ninety-nine students from two
      Cleveland Public Schools served as subjects. One school received a 15-week
      intervention program where teams of two medical students met with urban
      elementary schoolchildren three times a week for physical activity sessions. The
      other school served as a control and received no supplemental activity other than
      a regularly scheduled physical education class held once a week. We obtained
      field measurements of skinfold thickness, heart rate response to submaximal
      exercise, and sit and reach flexibility. RESULTS: The supplemental activity group
      showed significant improvements in flexibility, body composition, and heart rate
      response to submaximal exercise. CONCLUSIONS: This investigation indicates that a
      program of fitness activities conducted within the classroom can significantly
      improve levels of fitness in urban elementary schoolchildren.

PMID- 9532447
TI  - Race and ethnicity in research on infant mortality.
AB  - BACKGROUND AND OBJECTIVES: Race and ethnicity are variables frequently used in
      medical research. However, researchers employ race and ethnicity in different
      ways and with differing intent. This leads to confusion over the interpretation
      of racial or ethnic differences. This study sought to determine how race and
      ethnicity are used in research on infant mortality. METHODS: We did a structured
      literature review of original research related to infant mortality published
      between January 1995 and June 1996 and indexed in the Core Contents section of
      MEDLINE. RESULTS: The majority of articles (54%) mentioned race and ethnicity. US
      studies mentioned race or ethnicity more than non-US studies (80% versus 22%).
      Only one study defined the method used to determine the ethnicity of patients; no
      study defined race or the methodology used in determining patients' race.
      Researchers primarily used race and ethnicity to describe study populations. Some
      racial and ethnic identifiers may have been stigmatizing to the subjects studied.
      The second most common use of race or ethnicity was as a potential confounder.
      Only one article discussed racism as a contributing factor in infant mortality.
      CONCLUSIONS: There are several problems and ambiguities in the use of race and
      ethnicity in clinical research. Researchers who use racial or ethnic categories
      should do so for specified reasons and adopt clear definitions of the categories
      used.

PMID- 9532448
TI  - Disaggregating the effects of race on breast cancer survival.
AB  - BACKGROUND AND OBJECTIVES: This study examines differences in breast cancer
      survival between African-American and white women to determine whether there is a
      racial difference in survival after accounting for established influences on
      outcome, such as stage of cancer, health status, health behavior, utilization
      patterns, access to care, quality of care, and the doctor-patient relationship.
      METHODS: This study is a retrospective review of clinical records. The sample
      consists of 246 patients of three staff model HMOs who had mastectomies at stage
      II or above. Data on patient demographics, stage of cancer, health status, and
      health behavior and utilization, including preventive care, were extracted from
      patient records. Multivariate logistic regression was used to predict the
      determinants of advanced stage of cancer. Cox survival analysis was used to
      predict the determinants of survival. RESULTS: Missed appointments and stage of
      cancer were the key determinants of survival. The effect of race on survival was
      marginal after adjusting for these factors. Race, patients who missed
      appointments, and patients who delayed in reporting breast cancer symptoms were
      determinants of advanced stage. African-Americans were overrepresented among
      patients who missed appointments. CONCLUSIONS: Missed appointments was a
      determinant of both advanced stage and shorter survival. This measure is an
      important component of how race affects survival. Compliance with appointment
      keeping and alleviating reasons for noncompliance must be considered as factors
      in breast cancer survival.

PMID- 9532449
TI  - [Bacterial conjugative transposons].
AB  - Data on conjugative transposons of Gram-positive and Gram-negative bacteria are
      reviewed. Their organization and the mechanism of their transposition and
      mobilization of other replicons are considered. The transposition regulation by
      tetracycline and the role of conjugative transposons in bacterial gene transfer
      are briefly discussed.

PMID- 9532450
TI  - [Gene Nc73EF of Drosophila melanogaster encodes a protein highly homologous to E1
      subunit of human 2-oxoglutarate dehydrogenase].
AB  - The primary structure of the cDNA copy of the evolutionary conserved gene Nc73EF
      from the region 73EF of Drosophila melanogaster was determined. Gene Nc73EF was
      shown to encode a protein highly homologous to the E1 subunit of human 2
      oxoglutarate dehydrogenase, which catalyzes one of the key reactions of the Krebs
      cycle.

PMID- 9532451
TI  - [Cloning of large imperfect palindromes in circular and linear vectors].
AB  - Data on comparative analysis of cloning of large imperfect artificial palindromes
      and one natural palindrome in the circular pUC19 and linear pN15L vectors,
      constructed on the basis of temperate N15 bacteriophage minireplicon are
      presented. The artificial palindromes consisted of the two head-to-head oriented
      5:5-kb lambda bacteriophage DNA fragments interrupted by a short sequence of
      varied size. Natural palindrome was represented by the 12.5-kb BamHI fragment of
      Tetrahymena pyriformis ribosomal genes cluster. Integration of some artificial
      palindromes and a natural palindrome into a circular vector resulted in a
      considerable decrease of its copy number. This was assumed to result from
      cruciform formation mediated by supercoiling of a circular vector DNA. Thus, a
      linear is vector preferable in cloning of inverted repeated DNA sequences.

PMID- 9532452
TI  - [Cloning and sequencing of the chromosome fragment of Bacillus subtilis,
      complementary to the exoA mutation of Bacillus subtilis and sbcB of Escherichia
      coli].
AB  - A 3279-bp fragment of the Bacillus subtilis chromosome was cloned. This fragment
      completely restored exonuclease I activity in cells of the Escherichia coli Jm105
      strain, which contained the sbcB mutation, and suppressed repair damage in cells
      of this mutant. The cloned fragment fully complemented a mutation that decreased
      exonuclease I activity in Bac. subtilis KU647 and KU1020 strains leading to the
      restoration of enzymatic activity and mutant phenotype suppression. The
      nucleotide sequence of the Bac. subtilis gene encoding the structure of
      exonuclease I was determined. The amino-acid sequence of this enzyme proved to
      have 29.7% homology with the amino-acid sequence of E. coli exonuclease I.

PMID- 9532453
TI  - [Chromosome bridges and tailed nuclei in malignant cell populations].
AB  - Cell clones of the finite organospecific rat rhabdomyosarcoma RA-23 were selected
      in vivo for high and low frequency of interphase cells with chromosome bridges.
      After selection for high frequency of cells with bridges, the frequency of cells
      with anomalies of nuclear form sharply increased in the cell populations. These
      anomalies were manifested by long nuclear protrusions into the cytoplasm. This
      type of anomaly was termed tailed nuclei. In the studies populations of RA-23,
      the frequency of cells with "tailed" nuclei positively correlates with the
      frequency of interphase cells with chromosome bridges and the frequency of ana-
      and telophases with chromosome bridges. These parameters might be genetically
      associated: dicentric chromosomes form chromosome bridges in ana- and telophases
      of mitosis. Then, in some cases, the bridges are maintained, which result in the
      appearance of interphase cells with bridges, and, in other cases, the bridges are
      ruptured, which result in the appearance of cells with tailed nuclei.

PMID- 9532454
TI  - [Chromosome arrangements and cytogenetic differentiation of two species of
      African mice of the genus Mus (Rodentia, Muridae)].
AB  - Karyotypes of two African mouse species, Mus mahomet, 2n = 36, NFa = 34 (34A + XA
      + YA) and Mus sp. A, 2n = 34, NFa = 32 (32A + XA + YA), from five localities of
      the Bale Mountains National Park, Ethiopia, were analyzed. In both species all
      autosomes contained C-positive pericentromeric blocks. In M. mahomet,
      heterochromatin blocks of different chromosomes varied in size. In addition, the
      X chromosomes of both species contained a pericentromeric block and showed more
      intensive staining throughout the chromosome. The Y chromosome was two times
      larger in Mus sp. A than in M. mahomet and C-positive in both species.
      Comparative analysis of G-banding patterns revealed a similarity with respect to
      nine autosomes and the X chromosome. Autosome 1 of Mus sp. A was demonstrated to
      result from centromere-telomere fusion of two M. mahomet acrocentrics. The other
      five autosomes represent different linkage groups determining a specificity of
      the karyotypes. The karyotypes of M. mahomet and Mus sp. A were also compared
      with that of M. musculus. The evolution of M. mahomet and Mus sp. A karyotypes
      was shown to have involved structural rearrangements in 10 and 12 autosomes,
      respectively. The high karyological divergence confirmed molecular phylogenetic
      data. The cytogenetic differences T of M. musculus C from M. mahomet and Mus sp.
      A are high enough to different genera.

PMID- 9532455
TI  - [Distribution of HLA class I antigen in Finno-Ugrian populations of Russia
      (Mordovians and Maris)].
AB  - Distributions and gametic associations of HLA I antigens were studied in two
      Finno-Ugrian populations of Russia: Mordovians (300 subjects, including 148
      Erzyas and 152 Mokshas) and Maris (137 subjects). Regarding the Mordovian
      population, Erzya and Moksh subpopulations significantly differed from each other
      only in the frequency of the A9 antigen. However, the Mari and Mordovian
      populations differed from each other considerably. Maris exhibited higher
      frequencies of antigens A9, B27, and B40 and lower frequencies of B5, B8, and B16
      compared to Erzyas, as well as higher frequencies of A3, A28, B27, and B40 and
      lower frequencies of A10, B5, B8, B16, and B18 compared to Moksha. In addition,
      Erzyas, Mokshas, and Maris differed from one another in the gametic associations
      revealed. In general, our data indicated that the three populations, which
      display characteristic features of both Caucasoid and Mongoloid races, differ
      from one another with respect to the HLA genetic polymorphism. In all of the
      three populations, a positive association of the B27 antigen with
      spondylarthropathies (SAPs) was revealed. This confirms the hypothesis that B27
      is involved in the pathogenesis of some rheumatoid diseases.

PMID- 9532456
TI  - [Genetic analysis of the South Altaian population of the Mendur-Sokkon village,
      Altai Republic].
AB  - This study was a continuation of complex research on the gene pool of indigenous
      Siberian populations conducted at the Institute of Cytology and Genetics,
      Siberian Division, Russian Academy of Sciences. In the population of South
      Altaians from the Mendur-Sokkon village, Ust'-Kanskii raion, Altai Republic,
      polymorphism for the following genetic markers was studied: blood groups ABO,
      MNSs, Rhesus, Kell, Duffy, and P; erythrocyte acid phosphatase (AcP);
      phosphoglucomutase 1 (PGM1); haptoglobin (Hp); and transferrin (Tf). The genetic
      position of South Altaians relative to the populations of the European part of
      Russia, Siberia, and the Urals was estimated. It was demonstrated that the gene
      pool of the South Altaian population of Mendur-Sokkon possessed both Caucasoid
      and Mongoloid genetic characteristics, with the latter prevailing. Genetically,
      this population is most closely related to Mongols and Nentsis. The genetic
      distance between South and North Altaians was large; this agreed with earlier
      genetic data and confirmed anthropological and ethnographic evidence indicating
      that these two groups had different backgrounds and were at different stages of
      ethnogenesis.

PMID- 9532457
TI  - [Identification of marker chromosomes and translocations in man using a
      computerized diagnostic database and fluorescent in situ hybridization].
AB  - Cytogenetic analysis revealed five carriers of supernumerary marker chromosomes
      and two carriers of unbalanced chromosome translocations in patients of the
      medical genetic consultation clinic. A new method for exact identification of
      such chromosome rearrangements requiring additional molecular cytogenetic
      diagnosis was proposed. The method involves computer analysis of abnormal
      phenotypic traits with the use of diagnostic databases and fluorescent in situ
      hybridization (FISH) to DNA probes specific for the most probable computer
      selected chromosome syndromes. On average, the method allowed the number of
      necessary DNA probes to be decreased four times. In the tested patients,
      supernumerary marker chromosomes were shown to be derived from chromosomes 2, 9,
      and 15, and translocations were identified as dic(Y;18) and ins(6;21). Limited
      possibilities of using the method when (1) a chromosome syndrome is not clearly
      defined in a diagnostic system or (2) phenotypic expression of a marker
      chromosome is not significant are discussed. Presumably, the method will allow a
      reliable estimation of the efficiency of various diagnostic systems.

PMID- 9532458
TI  - Current materials and techniques for direct restorations in posterior teeth. Part
      2: Resin composite systems.
AB  - This paper, the second in a two-part review of direct materials and techniques
      for intracoronal restorations in posterior teeth, deals with resin composite
      systems. Based on a consensus view on appropriate applications for composites in
      posterior teeth, consideration is given to the selection of composite systems,
      indications for posterior composites in different populations, principles for
      cavity preparation, placement techniques, clinical performance and the use of
      posterior composites in the context of the changing pattern of dental disease and
      the need to expand existing knowledge. It is concluded that posterior composites
      have a place in everyday clinical practice, albeit relatively limited and that
      the time has come to actively pursue and realise the opportunities afforded by
      these materials.

PMID- 9532459
TI  - Oral health status of an industrial population in Romania.
AB  - The purpose of this survey was to assess the oral health situation of an
      industrial population in Romania. A total of 311 male and female employees (18-62
      years-of-age) were clinically examined according to the WHO Basic Methods
      criteria and responded to an oral health questionnaire on dental knowledge and
      health care habits. In the younger age groups, the amount of untreated dental
      caries was high (18-24 years: DT = 5.7, DMFT = 8.9) whereas missing teeth were
      prominent in older employees (45 years or more: MT = 7.6, DMFT = 11.9). At age 25
      44, 72 per cent had gingival bleeding and calculus. Dental knowledge was
      relatively poor, and 28 per cent of the participants indicated actual need for
      treatment. Dental visits within the previous 12 months were reported by 24 per
      cent of the employees, and 39 per cent had had a tooth extracted at their most
      recent visit. The study emphasises the need for reorientation of oral health care
      in Romania, and the relevance of industrial dental services for the
      implementation of oral health promotion and prevention is highlighted.

PMID- 9532460
TI  - Nutrition in dental education: a European perspective.
AB  - Previous studies have highlighted the diversity of levels of nutrition teaching
      in European Dental Schools, ranging from extensive courses in Scandinavia and the
      Netherlands to little or none in some other countries. A current survey has shown
      that whilst on average there has been a small increase in nutrition teaching
      since 1989, the profile over all is unchanged. The major exception however, is
      the UK, where nutrition teaching has improved substantially since the
      introduction of the extended preclinical curriculum in 1990. Despite improved
      living standards and better nutrition in much of Europe, nutrition is still an
      essential component of the dental curriculum. New problems such as erosion and
      obesity have arisen as a result of a diet of affluence and modern lifestyles.
      European Union guidelines on nutrition teaching would be helpful.

PMID- 9532462
TI  - Sweet preference, consumption of sweet tea and dental caries; studies in urban
      and rural Iraqi populations.
AB  - The objective of the present study was to explore the association between sweet
      preference and the levels of dental caries in a large sample of urban and rural
      children and young adults in Iraq. In addition, the relationship between caries
      levels and sweet tea consumption was investigated. Sweet preference was assessed
      using a free choice method while caries was measured by the DMFT index in 4,152
      males and females of differing ages living in urban and rural areas. A positive
      significant correlation between sweet preference and dental caries was found for
      both urban and rural populations. This relationship was stronger in the rural
      groups (r = +0.58, P < 0.001) than in the urban groups (r = +0.24, P < 0.001).
      The number of cups of tea consumed was positively correlated with the DMFT scores
      as was the number of spoonfuls of sugar taken in each cup of tea. Both these
      correlations were greater for the rural groups. These findings, together with
      those showing that sweet preference changes with exposure to sugars; the more
      sugars people consumed the higher their threshold for sweetness, indicates that
      exposure to sugar increases the intake sugar and the risk of dental caries.

PMID- 9532461
TI  - Self-assessed bleeding and plaque as methods for improving gingival health in
      adolescents.
AB  - The aim of this longitudinal study was to compare the effectiveness, in terms of
      cognitive and clinical changes, of two oral self-care promoting interventions
      based on a self-assessment of bleeding from gums or of presence of plaque.
      Adolescent students (age 14.0 + 0.7 years) from two health districts in Helsinki,
      Finland, participated in this one-year study. The self-assessment of bleeding
      group (n = 172) recorded bleeding during tooth brushing and inter-proximal
      cleaning with toothpicks on a single session. The self-assessment of plaque group
      (n = 156) recorded the presence of plaque with disclosing dye. Both programmes
      resulted in comparable clinical improvement in bleeding on probing over 9 months.
      Increased awareness of gingivitis was associated with clinical improvement. The
      subjects' socio-economic background, baseline gingival health status and age were
      statistically significantly associated with gingival health improvement during
      the follow-up. The results support earlier reports on self-assessment and suggest
      that both self-assessment approaches are beneficial for promoting gingival health
      in adolescents.

PMID- 9532463
TI  - Uniform requirements for manuscripts submitted to biomedical journals.
      International Committee of Medical Journal Editors.

PMID- 9532464
TI  - Extrapelvic endometriosis--an overview and case histories.
AB  - Extrapelvic endometriosis (EPE) is rare, and often associated with uterine
      procedures. Four cases of EPE are presented. The relationship between pelvic
      endometriosis and infertility is discussed. Pathogenesis, prevention, and
      treatment are explained, along with a review of the literature.

PMID- 9532465
TI  - Goserelin followed by assisted reproduction: results in infertile women with
      endometriosis.
AB  - OBJECTIVE: Demonstrate the usefulness of combined treatment of a Gn-RH agonist
      and assisted reproduction in the management of infertile women with
      endometriosis. DESIGN: A prospective evaluation of goserelin's action (Gn-RH(a))
      in the extension of endometriosis, of its suppression and clinical improvement,
      and in pregnancy rates after an immediate assisted reproduction program. SITE:
      Infertility clinic at a private hospital related to other university hospitals.
      PATIENTS: 18 infertile patients with laparoscopically-confirmed endometriosis.
      METHOD: All women were submitted to general laboratory tests, FSH, LH and
      estradiol measurements, and laparoscopy before and after treatment. All were
      treated for 6 months with goserelin and, when menstruating, the patients were
      submitted to an assisted reproduction program with a scheme of HMG + FSH + HCG.
      MAIN OUTCOME MEASURES: Improvement of endometriosis and achievement of pregnancy.
      RESULTS: An improvement of the endometriosis score was confirmed in 100% of the
      cases. The average pretreatment score of 44.8 points decreased to 18.3 after
      treatment. Similarly, the pain reported by eight of the patients practically
      disappeared after using the Gn-RH analogue. During treatment with goserelin, all
      women had amenorrhea. Their periods resumed in an average of 80.5 days after the
      last injection. In three (17.6%) cases, no follicular response was obtained, and
      stimulation was suspended. The remaining responses were good: eight GIFT
      procedures, four IVF-ET procedures and two IUIs resulted in eight pregnancies
      (57.1%), one of which terminated in an abortion (the patient became pregnant
      again). The eight pregnancies had good results: one was double and another
      quadruple. Most importantly, all pregnancies were achieved during the first
      treatment attempt. CONCLUSION: Combined treatment of goserelin with immediate
      assisted reproduction is a satisfactory procedure, which achieves a high
      percentage of pregnancies at the first try and with few abortions in cases of
      infertile women with endometriosis.

PMID- 9532466
TI  - Effect of norethindrone acetate in the treatment of symptomatic endometriosis.
AB  - OBJECTIVE: The purpose of the study was to evaluate the efficacy of norethindrone
      acetate (NA) treatment in 52 women with dysmenorrhea, dyspareunia, noncyclic
      pelvic pain who had a diagnosis of endometriosis by laparoscopy. RESULTS:
      Dysmenorrhea and noncyclic pelvic pain were relieved in 48/52 (92.3%) and 25/28
      (89.2%) of patients, respectively. Overall pain relief was obtained in 49/52
      (94.2%) of patients. Breakthrough bleeding, of variable severity, was the most
      common side effect experienced by 30 patients (57.6%); however, only 4 patients
      (7.7%) dropped out for this side effect. One other patient dropped out for severe
      breast tenderness, and three for noncyclic pelvic pain. In general, treatment was
      successful in 44/52 (84.5%) of patients with the above symptoms. CONCLUSION: NA
      seems to be a cost-effective alternative with relatively mild side effects in the
      treatment of symptomatic endometriosis.

PMID- 9532467
TI  - A spontaneous luteinizing hormone surge is beneficial in women with unexplained
      infertility undergoing controlled ovarian hyperstimulation without in vitro
      fertilization.
AB  - OBJECTIVE: To determine whether a spontaneous luteinizing hormone (LH) surge
      influences the pregnancy and miscarriage rate in women with unexplained
      infertility undergoing controlled ovarian hyperstimulation (COH) without in vitro
      fertilization. DESIGN: Retrospective cohort study. SETTING: Ovulation Induction
      Clinic, Royal Hospital for Women, Sydney, Australia. PATIENTS: 145 patients with
      unexplained infertility who underwent 374 cycles of COH. METHODS: Two types of
      ovarian stimulation protocols were used: human menopausal gonadotrophin (hMG)
      alone or hMG and clomiphene citrate (CC). A spontaneous LH surge occurred in 54%
      of the total cycles. All patients received human chorionic gonadotrophin, whether
      or not a spontaneous LH surge occurred. All cycles were covered by natural
      intercourse. MAIN OUTCOME MEASURES: Cycle pregnancy rate and miscarriage rate in
      cycles with or without a spontaneous LH surge. RESULTS: The cycle pregnancy rate
      of the LH surge group was significantly higher than that of the no LH surge group
      for CC/hMG cycles (16.4% and 4.3% respectively, p = 0.02) but not for hMG alone
      cycles (12.8% and 10% respectively, P > .05). The miscarriage rate was not
      significantly different between the LH surge group and no LH surge group in
      either the CC/hMG cycles (30% and 75% respectively, P > .05) or the hMG alone
      cycles (22% and 38% respectively, P > .05). CONCLUSIONS: In women with
      unexplained infertility undergoing COH with CC/hMG, the occurrence of a
      spontaneous LH surge is a favorable event associated with a significantly
      increased pregnancy rate. The data showed a lower miscarriage rate, but there was
      insufficient power to confirm or refute this result.

PMID- 9532468
TI  - Relationship of testicular volume to semen profiles and serum hormone
      concentrations in infertile Japanese males.
AB  - OBJECTIVE: We studied the relationship between testicular volume and semen
      quality and also between testicular volume and seminiferous tubular or Leydig
      cell function in infertile Japanese males. METHODS: The testicular volumes of 486
      infertile Japanese males were measured by an orchidometer. Semen samples were
      analyzed according to the guidelines of the World Health Organization. Serum
      concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH),
      and testosterone were measured by radioimmunoassay. The subjects were divided
      into 10 groups according to testicular volume, and the variables from each group
      were analyzed and compared. RESULTS: Testicular volume had the strongest positive
      correlation with sperm density, followed in decreasing order by total sperm count
      per ejaculate, total motile sperm count per ejaculate, and percentage of motile
      sperm. Testicular volume had the strongest negative correlation with serum FSH
      concentrations, followed by serum LH concentrations. In contrast, no significant
      correlations were found between testicular volume and semen volume or serum
      testosterone concentrations. Multiple regression analysis of dependence of
      testicular volume on semen profiles and serum hormone concentrations revealed
      that the only significant factor was serum FSH concentration. Sperm density was
      under the limit of normal in patients with a testicular volume of less than 30
      mL. In these patients, serum FSH concentrations were abnormally increased.
      Patients with a testicular volume of less than 10 mL were azoospermic, while
      volumes of less than 20 mL were associated with severe oligozoospermia.
      CONCLUSIONS: Testicular volume has a direct correlation with semen profiles, and
      the critical testicular volume indicating normal testicular function is
      approximately 30 mL. The measurement of testicular volume can be helpful for
      rapidly assessing fertility at the initial physical examination.

PMID- 9532469
TI  - The ocular manifestations of rheumatoid disease.
AB  - The inflammatory arthropathies that affect the eye most commonly are RA, JRA, and
      the seronegative spondyloarthropathies. These conditions not only cause
      devastating systemic findings but can be the source of damaging ocular disease.
      The inflammatory nature of these entities, with the accompanying liberation of
      mediators of inflammation, can result in a cycle of tissue destruction that
      culminates in blindness. The diseases reviewed can present first with systemic or
      ocular findings; thus, all physicians must be equipped with the appropriate
      knowledge to make accurate and timely diagnoses so that appropriate management
      strategies can be employed. The successful recognition and treatment of these
      conditions can prevent their associated systemic and ocular morbidity.

PMID- 9532470
TI  - Peripheral ulcerative keratitis and collagen vascular disease.

PMID- 9532471
TI  - Systemic lupus erythematosus and the eye.

PMID- 9532473
TI  - Angiogenic factors in the development of diabetic iris neovascularization and
      retinopathy.

PMID- 9532472
TI  - Diagnostic and therapeutic challenges of sarcoidosis.

PMID- 9532474
TI  - Retinal manifestations of aging.

PMID- 9532476
TI  - Metastatic tumors of the eye and orbit.

PMID- 9532475
TI  - Managing Graves' orbitopathy.

PMID- 9532477
TI  - Ocular manifestations of multiple sclerosis.

PMID- 9532478
TI  - Corneal manifestations of metabolic diseases.

PMID- 9532479
TI  - Vitamin A deficiency and its effects on the eye.

PMID- 9532480
TI  - Metabolic syndromes with ocular and renal consequences.

PMID- 9532481
TI  - Systemic diseases manifesting as exudative retinal detachment.

PMID- 9532482
TI  - Retinal manifestations of gastrointestinal conditions.

PMID- 9532483
TI  - Chlamydial ocular diseases.

PMID- 9532484
TI  - Blackflies and whitewater: onchocerciasis and the eye.

PMID- 9532485
TI  - AIDS and the anterior segment.

PMID- 9532486
TI  - AIDS and the posterior segment.

PMID- 9532487
TI  - Chemical, physical, and sensory characteristics of mozzarella cheese fortified
      using protein-chelated iron or ferric chloride.
AB  - Mozzarella cheese containing 25 and 50 mg of iron/kg of cheese was manufactured
      from milk that had been fortified with casein-chelated iron, whey protein
      chelated iron, or FeCl3. Chemical, physical, and sensory characteristics were
      compared with those of a control cheese. Physical properties were assessed by
      testing melting, apparent viscosity, and browning of heated cheese. Cheeses were
      evaluated by trained panelists for the presence of metallic flavors, oxidized
      flavors, and other undesirable flavors. Addition of 25 mg iron/kg of cheese had
      no effects on the physical properties of Mozzarella cheese. Apparent viscosity of
      cheese fortified with 50 mg of iron/kg of cheese tended to be slightly higher
      than the control cheese, although this difference was not statistically
      significant at all storage times. Cook color was not affected by iron
      fortification. No increase in chemical oxidation (measured using thiobarbituric
      acid assay) was observed between the control and iron-fortified cheeses. Slight
      but statistically significant increases in metallic flavors, oxidized flavors,
      and off-flavors in the iron-fortified cheese were observed by the trained sensory
      panel, but the flavor defects were of very low intensity. For metallic flavors,
      oxidized flavors, and off-flavors, the control cheese scored 1.5, 1.5, and 1.3,
      respectively; the iron-fortified cheese scored 2.1, 2.0, and 1.6 based on a nine
      point scale (where 1 = not perceptible to 3 = slightly perceptible). Sensory
      scores for iron-fortified cheese made using casein-chelated iron or whey protein
      chelated iron was not significantly different from those of cheese made using
      ferric chloride. When used on pizza, consumer panels rated the iron-fortified
      cheeses as comparable with the control cheese.

PMID- 9532488
TI  - Milk catalase activity as an indicator of thermization treatments used in the
      manufacture of cheddar cheese.
AB  - Pilot-scale studies were carried out to determine the effect of different heat
      treatments on catalase activity during the manufacture and maturation of Cheddar
      cheese. Three trials were conducted to monitor catalase activity using disk
      flotation and polarographic methods. Cheese was manufactured from raw milk and
      from milk that had been treated at 60, 65 and 72 degrees C for 16 s using a high
      temperature, short time heat exchanger. Catalase activity was also determined in
      samples of commercial milk and in samples of mild, medium, sharp, and extra sharp
      Cheddar cheeses obtained from different manufacturers in order to verify that the
      enzyme could be used as an indicator of the type of heat treatment applied to
      cheese milk. Catalase activity was present in cheese made from raw milk but was
      only present at low concentrations in cheese manufactured from thermized milk.
      However, high catalase activity was observed in commercial samples of sharp and
      extra sharp Cheddar cheese that was apparently due to the growth of catalase
      producing yeasts in the cheese during maturation.

PMID- 9532489
TI  - Growth, viability, and proteolytic activity of bifidobacteria in whole camel
      milk.
AB  - Four species of bifidobacteria were evaluated for growth, viability, and
      proteolytic activity in whole camel milk, and comparison was made with whole cow
      milk. Growth of all species in either whole milk was characterized by the
      appearance of two logarithmic phases following anaerobic incubation at 37 degrees
      C for 36 h. The growth rate of Bifidobacterium longum 15,707 was higher in camel
      milk than in bovine milk and was higher for Bifidobacterium angulatum 27,535 in
      bovine milk than in camel milk. Bifidobacterium bifidum 2715 and Bifidobacterium
      breve 2258 showed the same trend as B. angulatum 27,535 after 16 h of
      postinoculation. Viable counts of all species except B. bifidum 2715 increased in
      the fermented whole milks during the first 3 d of storage at 4 degrees C.
      However, such counts did not change in unfermented milk, except for B. longum
      15,707, which showed an increase in viable counts after 12 d of storage.
      Viability of all species in both fermented and unfermented milks was unaffected
      during refrigerated storage for 15 d. All species except B. longum 15,707 showed
      higher proteolytic activity in fermented camel milk than in bovine milk. However,
      proteolytic activity of all species except B. breve 2258 started at d 9 in
      unfermented camel milk only and increased sharply until the end of the storage
      period.

PMID- 9532490
TI  - Measures of estrus detection and pregnancy in dairy cows after administration of
      gonadotropin-releasing hormone within an estrus synchronization program based on
      prostaglandin F2 alpha.
AB  - The objective of this study was to assess the use of GnRH in a controlled
      breeding program (7 d prior to the second of two injections of PGF2 alpha, 14 d
      apart) as a means to improve the expression and detection of estrus, first
      service conception rate, and overall pregnancy rate of lactating dairy cows. On
      17 farms, 348 cows were assigned randomly to either of two breeding programs
      prior to first insemination. Cows in both programs received PGF2 alpha
      approximately 2 wk prior to the end of a herd-specific voluntary waiting period
      for breeding. One group received GnRH 1 wk later, 7 d prior to the second of two
      injections of PGF2 alpha. Control cows received saline and a second injection of
      PGF2 alpha at corresponding times. Cows were observed for 7 d and were bred by
      artificial insemination following detection of estrus. There were no differences
      between programs in estrus detection rate, observed signs of estrus, conception
      rate, days to first service, or interval from calving to conception. The means
      and standard deviations of the interval from PGF2 alpha to estrus were not
      different between programs. Administration of GnRH 1 wk prior to PGF2 alpha did
      not alter the expression of estrus or fertility in lactating dairy cows. In this
      study population, no advantage was found for the addition of GnRH to a controlled
      breeding program that was based on two administrations of PGF2 alpha at a 14-d
      interval.

PMID- 9532492
TI  - Effects of timed insemination and supplemental beta-carotene on reproduction and
      milk yield of dairy cows under heat stress.
AB  - In three experiments, we tested the efficacy of timed artificial insemination
      (AI) and beta-carotene supplementation for improvement of reproduction and milk
      yield. Experiments 1 and 2 were conducted during hot months, and Experiment 3 was
      conducted during cooler months. Cows were fed rations supplemented with beta
      carotene at 0 or 400 mg/d per cow for > or = 15 d before the first AI. Cows were
      inseminated at each observed estrus after 70 d (Experiment 1) or at 50 d
      postpartum (Experiments 2 and 3) or were included in a timed AI program [d 0
      (i.e., approximately 40 or 60 d postpartum), 8 micrograms of GnRH agonist; d 7,
      25 mg of PGF2 alpha; d 9, 8 micrograms of GnRH agonist; d 10, AI] for first
      breeding. Pregnancy rate at first AI was similar among groups, but the percentage
      of cows that were pregnant by 90 d postpartum was greater for cows in the timed
      AI group in Experiments 1 (16.6% vs. 9.8%) and 2 (34.3% vs. 14.3%) but not in
      Experiment 3 (24.1% vs. 28.7%). Overall, beta-carotene had no effect on
      reproductive function. For cows fed supplemental beta-carotene for > or = 90 d,
      however, pregnancy rate at 120 d postpartum was increased in Experiment 1 (35.4%
      vs. 21.1%). In all experiments, beta-carotene increased cumulative milk yield on
      the last test day by 6 to 11%. In conclusion, timed AI can improve pregnancy
      rates during periods of heat stress. Supplemental beta-carotene may increase
      pregnancy rates for cows in the summer and can increase milk yield.

PMID- 9532491
TI  - Mechanisms regulating prostaglandin F2 alpha secretion from the bovine
      endometrium.
AB  - The mechanism that regulates luteolytic PGF2 alpha secretion as stimulated by
      oxytocin is thought to involve induction of the inositol (1,4,5)-trisphosphate
      diacylglycerol second messenger system, which mobilizes intracellular calcium and
      activates protein kinase C. In Experiment 1, endometrial explants taken from
      heifers on d 18.5 to 19.5 postestrus had increased PGF2 alpha secretion after
      treatment with 1 microM calcium ionophore A23187 to increase intracellular
      calcium, 100 nM phorbol 12-myristate 13-acetate to activate protein kinase C, and
      100 nM oxytocin. The stimulatory effects of oxytocin and calcium ionophore A23187
      plus phorbol 12-myristate 13-acetate did not differ from each other. In
      Experiment 2, endometrial explants taken from cows on d 18.5 to 19.5 postestrus
      had increased PGF2 alpha secretion after treatment with 0.2 and 2 microM
      thapsigargin to mobilize intracellular calcium that was sensitive to inositol
      (1,4,5)-trisphosphate. Secretion of PGF2 alpha was also increased by 100 nM
      oxytocin and was influenced by the interaction of thapsigargin and oxytocin such
      that 100 nM oxytocin did not further increase the secretion of PGF2 alpha in the
      presence of 2 microM thapsigargin. In Experiment 3, 100 nM oxytocin stimulated
      greater production of inositol trisphosphate and total inositol phosphates in the
      endometrium of cyclic cows than in the endometrium of pregnant cows on d 16.5 to
      17.0 postestrus, although luteolysis was not yet initiated in the cyclic cows.
      These results are consistent with the hypothesis that the activation of the
      inositol (1,4,5)-trisphosphate-diacylglycerol second messenger system by oxytocin
      is involved in the stimulation of PGF2 alpha secretion from the endometrium
      during late diestrus in cows.

PMID- 9532493
TI  - Antibiotics commonly used to treat mastitis and respiratory burst of bovine
      polymorphonuclear leukocytes.
AB  - The in vitro effects of six doses (2 x 10(-3) to 2 x 10(-8) M) of antimicrobial
      drugs that are frequently used in udder infusions on the capacity of bovine blood
      polymorphonuclear neutrophilic leukocytes to generate reactive oxygen species
      were studied by the measurement of luminol-dependent chemiluminescence after
      stimulation with phorbol 12-myristate 13-acetate. All drugs, except cloxacillin,
      significantly decreased chemiluminescence at the highest dose. Doxycyline induced
      the most severe inhibition, followed by neomycin and dihydrostreptomycin. The
      effect of ampicillin was due to the scavenging of reactive oxygen species and
      interactions with luminol. The inhibition observed with oleandomycin, neomycin,
      lincomycin, and dihydrostreptomycin was not due to direct effects on the
      production of oxidative metabolites but rather to interference with other
      components involved in the production of light, such as interference with the
      interaction between luminol and the myeloper-oxidase-H2O2-halide system. The
      deleterious effects of doxycycline can be explained by several factors: decreased
      production of superoxide, yellow color, the scavenging of reactive oxygen
      species, and Ca2+ chelating effect. In conclusion, the results of this study show
      that antibiotics may affect neutrophil function at concentrations that are
      reached in the mammary gland after local and repeated administration.

PMID- 9532494
TI  - Incidence of clinical mastitis in dairy herds grouped in three categories by bulk
      milk somatic cell counts.
AB  - Incidence of clinical mastitis was studied in 274 herds grouped in three
      categories by bulk milk somatic cell count (SCC). Mean incidence rate of clinical
      mastitis was 0.278, 0.257, and 0.252 cases per 365 cow-days at risk in herds with
      low (< or = 150,000), medium (150,000 to 250,000), and high (250,000 to 400,000
      cells/ml) bulk milk SCC, respectively. The incidence rate of clinical mastitis
      was not different among the three categories. Variance in the incidence of
      clinical mastitis among herds increased as bulk milk SCC decreased. Clinical
      mastitis caused by Gram-negative pathogens, such as Escherichia coli, Klebsiella
      spp., or Pseudomonas spp., occurred more often in herds with a low bulk milk SCC.
      Clinical mastitis caused by Staphylococcus aureus, Streptococcus dysgalactiae,
      and Streptococcus agalactiae occurred more often in herds with a high bulk milk
      SCC. Systemic signs of illness caused by clinical mastitis occurred more often in
      herds with a low bulk milk SCC. Both overall culling rate and culling rate for
      clinical mastitis were not different among groups catergorized by bulk milk SCC.
      In herds with a high bulk milk SCC, however, more cows that produced milk with a
      high SCC were culled. In herds with a low bulk milk SCC, more cows were culled
      for teat lesions, milkability, udder shape, fertility, and character than were
      cows in herds with a high bulk milk SCC. In herds with a low bulk milk SCC, cows
      were also culled more for export and production reasons.

PMID- 9532495
TI  - Risk factors for clinical mastitis in a random sample of dairy herds from the
      southern part of The Netherlands.
AB  - The incidence of clinical mastitis in dairy cows was estimated in 171 randomly
      selected dairy herds from the southern part of The Netherlands. A total of 1103
      quarter cases was reported. The mean annual incidence rate was 12.7 quarter
      cases/yr per 100 cows. The modeling incidence rate of clinical mastitis at the
      herd level indicated that a number of risk factors were associated with a higher
      rate of clinical mastitis: one or more cows that were leaking milk, one or more
      cows with trampled teats, no disinfection of the maternity area after calving,
      consistent use of post-milking teat disinfection, Red and White cattle (Meuse
      Rhine-Yssel) as the predominant breed, and an annual bulk milk somatic cell count
      < 150,000 cells/ml. The following risk factors were associated with a higher rate
      of clinical mastitis caused by Escherichia coli: cows with trampled teats, no
      disinfection of the maternity area after calving, consistent use of post-milking
      teat disinfection, use of a thick layer of bedding in the stall, and the
      stripping of foremilk before cluster attachment. The following risk factors were
      associated with a higher rate of clinical mastitis caused by Staphylococcus
      aureus: Red and White cattle (Meuse-Rhine-Yssel) as the predominant breed, cows
      with trampled teats, the stripping of foremilk before cluster attachment, no
      regular disinfection of the stall, no regular replacement of stall bedding, and
      an annual bulk milk somatic cell count < 150,000 cells/ml.

PMID- 9532496
TI  - Effect of monensin on milk production by Holstein and Jersey cows.
AB  - Effects of the administration of monensin via concentrates to dairy cows were
      studied in two trials. In one trial, 64 Holstein cows were assigned to four
      groups that received 0, 150, 300, or 450 mg/d of monensin from 5 to 24 wk
      postpartum. Milk production tended to increase (4.0, 3.3, and 5.4%, respectively)
      for the three groups of treated cows. Fat content was decreased by 0.09, 1.89,
      and 4.09 g/kg, respectively, for these same three groups. The effect on protein
      content was small and nonsignificant. Feed intake was reduced in treated cows,
      although not significantly, and feed efficiency was improved by monensin. In a
      confirmatory trial, 58 Holstein and 22 Jersey cows were allocated either to a
      control group or to a treatment group that received 300 mg/d of monensin from 5
      to 36 wk postpartum during the first lactation and from 2 wk before calving to 36
      wk postpartum during a subsequent lactation. During the first lactation, cows in
      the treatment group showed a 7% increase in milk production, a relative decrease
      (1.4 g/kg) in milk fat content, and equal protein content compared with cows in
      the control group. Body weight gain and body condition scores near the end of the
      treatment period were higher for cows in the treatment group. A decrease in blood
      ketone concentrations was found between 7 and 56 d of lactation. Treatment
      effects on milk production differed between breeds and within genetic lines.
      Jersey cows were less responsive than were Holstein cows, and Holstein cows with
      a high ratio of breeding values for protein and fat showed larger milk production
      responses. Results from the second lactation showed similar differences between
      the two groups as did those from the first lactation.

PMID- 9532497
TI  - No evidence for basolateral secretion of milk protein in the mammary gland of
      lactating goats.
AB  - Recent research suggests that a small percentage of milk proteins may be secreted
      basolaterally, which would have implications for our work on the permeability of
      tight junctions in the mammary epithelium. In our work, the presence of alpha
      lactalbumin (LA) or lactose in plasma is used as an indicator of permeability.
      The aim of this study was to examine basolateral secretion by determining the
      presence of milk proteins in efferent mammary lymph. Five Saanen goats were
      fitted with mammary lymph catheters and were administered intramammary isosmotic
      bolus infusions of sucrose control solutions or ethylene glycolbis(beta
      aminoethyl ether)-N,N,N',N'-tetraacetic acid to induce leaky tight junctions.
      Lymph samples were collected before and approximately 5 h after infusion. Lymph
      was analyzed by Western blotting for the presence of alpha-casein (CN), beta-CN,
      and alpha-LA No alpha-CN or beta-CN was detected in lymph, but alpha-LA was
      detected in all lymph samples. Moreover, the signal was much stronger in samples
      from goats that were treated with ethylene glycol-bis(beta-aminoethyl ether)
      N,N,N',N'-tetraacetic acid, and concentrations of alpha-LA in lymph were
      significantly increased with this treatment. These changes and the absence of
      casein in lymph suggest increased permeability of tight junctions rather than
      basolateral secretion. In summary, these data do not support basolateral
      secretion.

PMID- 9532498
TI  - Evaluation of five cowside tests for use with milk to detect subclinical ketosis
      in dairy cows.
AB  - The objective of this study was to evaluate the characteristics of five ketone
      tests for use with milk to detect subclinical ketosis [defined as > 1200 mumol of
      beta-hydroxybutyrate (BHBA)/L of blood] in dairy cows. The tests studied were the
      Ketolac BHB strip to detect BHBA (Hoechst, Unterschleissheim, Germany) and four
      tests based on sodium nitroprusside to detect acetoacetate (Rothera tests)
      [Ketostix strip (Bayer, Etobicoke, ON, Canada), Bioketone powder (Societe d'
      Analyses Biopharmaceutiques, Laval, QC, Canada), Ketocheck powder (Great States,
      St. Joseph, MO), and Utrecht powder (University of Utrecht, Utrecht, The
      Netherlands)]. Milk samples (n = 529) from 266 cows in 25 Ontario dairy herds
      were used for this investigation. The Ketolac BHB strip at 50 and 100 mumol of
      BHBA/L of milk showed sensitivities of 92 and 72%, respectively. This test was
      more sensitive for subclinical ketosis than were any of the Rothera tests. The
      sensitivities of the Rothera tests were 43, 33, 28, and 5%, respectively, for
      Utrecht powder, Bioketone powder, Ketocheck powder, and Ketostix strip. The
      Rothera tests were highly specific, as was the Ketolac BHB strip at 200, 500, and
      1000 mumol of BHBA/L of milk (specificity, > 97%). The prevalence of subclinical
      ketosis was highest during the first 6 wk of lactation, and a peak was detected
      during the 2nd wk of lactation. Of the tests evaluated in this study, Ketolac BHB
      strip was the most useful to monitor subclinical ketosis in dairy herds.

PMID- 9532499
TI  - Proteolysis during ensilage of forages varying in soluble sugar content.
AB  - The effect of contrasting concentrations of water-soluble carbohydrates of
      herbage on silage fermentation and composition was examined using grass with high
      [250 g/kg of dry matter (DM)] concentrations of water-soluble carbohydrates and
      grass and clover with low (66 g/kg of DM) concentrations of water-soluble
      carbohydrates. Herbages were ensiled untreated, after inoculation with lactic
      acid bacteria, or after treatment with formic acid. Good quality silages were
      produced from herbage with high concentrations of water-soluble carbohydrates,
      regardless of treatment, and all pH values were below 3.7 after 90 d of ensilage.
      However, the silage formed from inoculated herbage had a significantly lower
      concentration of ammonia N and a significantly higher proportion of residual
      ribulose-1,5-bisphosphate carboxylase compared with the other two silages. Fast
      protein liquid chromatography (Pharmacia, Uppsala, Sweden) was used to measure
      ribulose-1,5-bisphosphate carboxylase, and measurement of true plant protein
      fractions in herbage and silage showed benefits over traditional measurements
      such as the measurement of N and ammonia N. Herbages with low concentrations of
      water-soluble carbohydrates produced inferior quality silages that had lower
      ribulose-1,5-bisphosphate carboxylase contents and higher ammonia N contents,
      regardless of treatment; few significant differences were observed among
      treatments. Under good ensiling conditions, when available water-soluble
      carbohydrate is adequate, the use of inoculants can improve fermentation
      characteristics and increase the ribulose-1,5-bisphosphate carboxylase content of
      silages. However, when the herbage has low concentrations of water-soluble
      carbohydrates, even in inoculated herbages, lactic acid bacteria may follow a
      heterofermentative pathway instead of a homofermentative pathway, which can
      result in a decrease in silage quality and a reduction in intact ribulose-1,5
      bisphosphate carboxylase.

PMID- 9532500
TI  - Ruminal degradation, amino acid composition, and estimated intestinal
      digestibilities of four protein supplements.
AB  - Blood meal, canola meal, corn gluten meal, and menhaden fish meal were weighed
      into dacron bags for incubation in the rumens of two ruminally cannulated
      Holstein cows on 3 d for 0, 3, 6, 12, 18, and 24 h. Both the original feeds and
      the residues remaining after 12 h were analyzed for amino acid (AA) content.
      Canola meal was degraded the most extensively in the rumen, and blood meal was
      degraded the least extensively. Intestinal digestibilities estimated using an
      enzymatic in vitro technique were all high; canola meal was estimated to have the
      lowest intestinal digestibility, and corn gluten meal was estimated to have the
      highest intestinal digestibility. The AA profile of the 12-h residues differed
      only slightly from the AA profile of the original protein supplements. A
      comparison of the AA profiles of feed residues with milk protein showed that
      isoleucine was the first-limiting AA in blood meal, canola meal, and fish meal,
      and lysine was the first-limiting AA in corn gluten meal. Although canola meal
      was extensively degraded in the rumen, its 12-h residue still provided an
      estimated AA profile to the intestinal tract that was closest to the AA profile
      of milk protein. Blood meal and corn gluten meal are good sources of ruminally
      undegradable protein but are deficient in some AA and should probably be fed only
      in combination with other protein sources that complement their AA profiles.

PMID- 9532501
TI  - Effect of soybean hulls, soy lecithin, and soapstock mixtures on ruminal
      fermentation and milk composition in dairy cows.
AB  - Two experiments were conducted to determine effects of soybean hulls, soy
      lecithin, and soapstock mixtures on ruminal fermentation, milk composition, and
      ruminal microbial populations. In Experiment 1, 20 Holstein dairy cows were
      assigned to one of five total mixed rations (TMR) in replicated 5 x 5 Latin
      squares to measure the effect of TMR on intake and milk composition. Four
      ruminally fistulated cows were used in a 4 x 5 Youden square to measure the
      effect of TMR on ruminal fermentation. The TMR consisted of 40 or 50% alfalfa and
      corn silages, 13% soybean hulls, and 47 or 37% of a concentrate containing either
      2.25% soybean oil; 2.25% lipid from a mixture of soybean hulls, soy lecithin, and
      soapstock; or no added lipid. The ratios of soy lecithin to soapstock evaluated
      were 1:1, 2.5:1, and 4:1 (dry basis). The TMR containing soy lecithin and
      soapstock at ratios of 1:1 and 2.5:1 resulted in higher milk C18:2 than did the
      soybean oil TMR. Rate of ruminal NDF digestion of soybean hulls was reduced for
      the soybean oil TMR. In Experiment 2, a semi-continuous culture system was used
      to determine effects of soybean oil or an optimal mixture of soy lecithin and
      soapstock (1:1, wt/wt) on fermentation of soybean hulls and microbial
      populations. The TMR containing the lipid mixture increased the ratio of acetate
      to propionate compared with the TMR containing soybean oil and resulted in higher
      total protozoal counts than did the control TMR. The TMR containing mixtures of
      soy lecithin and soapstock at ratios of 1:1 and 2.5:1 elevated milk C18:2, and no
      negative effect on NDF digestion was detected, indicating some degree of ruminal
      protection.

PMID- 9532503
TI  - Evaluation of corn distillers grains and ruminally protected lysine and
      methionine for lactating dairy cows.
AB  - Twelve multiparous Holstein cows averaging 57 d (36 to 77 d) postpartum at the
      start of the experiment were utilized in a replicated 4 x 4 Latin square design.
      Dietary protein supplements were 1) soybean meal, 2) soybean meal plus ruminally
      protected Lys and Met, 3) corn distillers grains, and 4) corn distillers grains
      plus ruminally protected Lys and Met. Dry matter intakes were lower for cows fed
      diets containing soybean meal than for cows fed diets containing corn distillers
      grains. Milk yield increased with the corn distillers grains (34.3, 34.0, 35.3,
      and 36.7 kg/d for cows fed diets 1 through 4, respectively), especially when
      supplemented with ruminally protected Lys and Met. Milk protein yield and
      percentage were increased by amino acid supplementation. Milk fat yield and
      percentage were unaffected by diet. The only milk protein fraction affected was
      nonprotein N, which was lower in the milk of cows fed corn distillers grains.
      Lysine, Met, and Phe were indicated as the most limiting amino acids for all
      diets when using amino acid extraction efficiency and transfer efficiency to
      indicate limiting amino acids. When corn distillers grains were supplemented with
      ruminally protected Lys and Met, milk yield and milk protein yield and percentage
      increased because the diet containing corn distillers grains was probably
      deficient in Lys.

PMID- 9532502
TI  - Fatty acid profile and physical properties of milk fat from cows fed calcium
      salts of fatty acids with varying unsaturation.
AB  - Holstein cows (n = 24) averaging 42 d in milk were used in a randomized complete
      block design during a 4-wk trial. A control total mixed ration (TMR) was compared
      with TMR supplemented with Ca salts of fatty acids from canola oil, soybean oil,
      or linseed oil. The three vegetable oils were progressively more unsaturated; the
      dominant fatty acids were, respectively, cis-delta-9-C18:1, C18:2, and C18:3.
      Apparent total tract digestibility of dry matter, crude protein, ether extract,
      and neutral detergent fiber was higher for rations containing Ca salts than for
      the control ration. Milk yield increased linearly as the unsaturation of the
      dominant fatty acid in the Ca salts increased. Milk fat percentage was reduced
      when Ca salts were added to the rations. The addition of Ca salts to the ration
      decreased the proportions of saturated fatty acids that contained C6 to C16 and
      increased the proportions of C18:0, cis-delta-C18:1, and trans-delta-11-C18:1 in
      milk fat. Proportions of C18:2 and C18:3 increased linearly, and cis-delta-9
      C18:1 decreased linearly, as the unsaturation of the dominant fatty acid in the
      Ca salts increased. The proportion of fat that was liquid at 5 degrees C was
      higher for butter from cows fed diets containing Ca salts, but the proportion of
      liquid fat at 20 degrees C was not affected. Calcium salts of unsaturated fatty
      acids added to the diets of dairy cows improved the thermal properties of milk
      fat.

PMID- 9532504
TI  - Forage of different physical forms in the diets of lactating Granadina goats:
      nutrient digestibility and milk production and composition.
AB  - To determine whether the energy balance of goats or characteristics of the diet
      consumed were the principal factors that determined milk production, feeding and
      digestion trials were carried out using two groups of 5 Granadina goats. The
      concentrate fraction of both diets was the same, but the forage fraction of the
      diets differed. In diet 1, the forage was in the form of long alfalfa hay, and,
      in diet 2, forage was in the form of pelleted alfalfa. Intake and the forage to
      concentrate ratio of the two diets were not significantly different, although
      diet 2 was more digestible. The amount of fat and protein in the milk depended on
      energy intake and not on dietary treatment. The milk protein of goats fed diet 2
      was higher in casein. No sensible differences were noted in the fatty acid
      composition of the milk. Nitrogen and metabolizable energy utilization for milk
      production was greater for goats fed diet 2. According to the results obtained,
      it would seem advantageous to use pelleted alfalfa rather than alfalfa hay in the
      diets of goats.

PMID- 9532505
TI  - Effect of dietary energy and protein concentration on the concentration of milk
      urea nitrogen in dairy ewes.
AB  - To study the effects of dietary crude protein (CP) and energy on milk urea N
      concentrations in dairy sheep, eight pelleted total mixed rations were prepared
      to obtain two levels of energy density (1.65 and 1.55 Mcal of net energy for
      lactation per kilogram of dry matter for high energy and low energy rations,
      respectively) and four concentrations of CP within each energy level (mean CP
      concentrations, 14.0, 16.4, 18.7, and 21.2% of dry matter). The experimental
      design consisted of two 4 x 4 Latin squares (one per energy level) with two
      replications per treatment within each 3-wk period. Milk urea N concentrations
      were similar between dietary energy levels. Within each energy level, milk urea N
      was linearly and positively associated with dietary CP content and intake (range
      of milk urea N concentrations, 12.2 to 25.8 mg/dl for ewes fed high energy
      rations and 12.9 to 26.7 mg/dl for ewes fed low energy rations). The comparison
      of these results with those from other trials suggested that milk and blood urea
      N concentrations are closely correlated with dietary CP concentrations and less
      closely correlated with dietary CP intake. Our results suggest that milk or blood
      urea N concentrations can be used as indicators of protein metabolism and intake
      of lactating ewes.

PMID- 9532506
TI  - Evaluation of National Research Council and Cornell Net Carbohydrate and Protein
      Systems for predicting requirements of Holstein heifers.
AB  - This experiment evaluated the effects of prepubertal energy intake and dietary
      protein source on average daily gain of Holstein heifers. Holstein heifers (n =
      273) were assigned to one of three dietary energy treatments that were designed
      to achieve average daily gains of 0.6, 0.8, and 1.0 kg/d from 90 to 320 kg of
      body weight. Within each energy treatment, heifers were assigned to diets that
      were supplemented with animal and plant proteins or plant protein and urea. Diets
      were formulated using the Cornell Net Carbohydrate and Protein System. Actual
      mean daily gains by heifers on each energy treatment were 0.68, 0.83, and 0.94
      kg/d and were not affected by protein source. Undegradable intake protein was
      predicted by the Cornell Net Carbohydrate and Protein System to be adequate to
      support the observed daily gain that was allowed by the amount of energy in the
      diet and was 13 to 25% lower than the recommendations for undegradable intake
      protein by the National Research Council. These results suggested that
      requirements for undegradable intake protein may be met at concentrations that
      are less than 35% of the dietary crude protein. Energy equations from the
      National Research Council and Cornell Net Carbohydrate and Protein System were
      evaluated and accounted for 87 and 86% of the variation in body weight gain that
      was allowed by the amount of energy in the diet with biases of -7.7 and -5.7%,
      respectively. The Cornell Net Carbohydrate and Protein System has the primary
      advantage of improved accuracy in the prediction of nutrient requirements in each
      unique production situation.

PMID- 9532507
TI  - Effects of three prepubertal body growth rates on performance of Holstein heifers
      during first lactation.
AB  - The effects of body weight (BW) gain, different sources of protein during the
      prepubertal period (90 to 320 kg of BW), and the performance of Holstein heifers
      during their first lactation were studied. Heifers (n = 273) were assigned to one
      of three dietary energy treatments that were designed to achieve average daily
      gains of 0.6, 0.8, and 1.0 kg/d. Within each energy treatment, different protein
      sources (plant protein and urea or both plant and animal proteins) were imposed.
      Actual average daily gains by heifers on each energy treatment were 0.68, 0.83,
      and 0.94 kg/d for heifers that were fed diets formulated for average daily gains
      of 0.6, 0.8, and 1.0 kg/d, respectively, which allowed the following ages at
      first calving: 24.5, 22.0, and 21.3 mo. Breeding was initiated when heifers
      weighed approximately 340 kg. Protein sources did not affect average daily gain
      or milk yield. Analysis of the preplanned comparisons of actual 305-d and 4% fat
      corrected milk yields indicated that yield was significantly reduced for heifers
      grown at 0.94 kg/d (9387 and 8558 kg, respectively) compared with that of heifers
      grown at 0.68 kg/d (9873 and 9008 kg, respectively). However, further regression
      analysis of fat-corrected milk and residual milk from a test day model on
      prepubertal BW gain only explained 8 and 2% of the variation in milk yield,
      respectively. Postcalving BW and body condition score were different among
      treatments. Posttreatment factors, such as postcalving BW, accounted for more of
      the variation in milk yield than did prepubertal BW gain. Prepubertal BW gains,
      when evaluated on a continuum from 0.5 to 1.1 kg/d, explained little of the
      variation in milk yield; therefore, BW gain during the prepubertal period did not
      significantly affect milk yield during first lactation.

PMID- 9532508
TI  - Characterization of the 3' end of the gene for bovine factor XI.

PMID- 9532509
TI  - Variances of direct genetic effects, maternal genetic effects, and cytoplasmic
      inheritance effects for milk yield, fat yield, and fat percentage.
AB  - Milk yield, fat yield, and fat percentage during the first three lactations were
      studied using New York Holsteins that were milked twice daily over a 305-d,
      mature equivalent lactation. Those data were used to estimate variances from
      direct and maternal genetic effects, cytoplasmic effects, sire by herd
      interaction, and cow permanent environmental effects. Cytoplasmic line was traced
      to the last female ancestor using DHI records from 1950 through 1991. Records
      were 138,869 lactations of 68,063 cows calving from 1980 through 1991. Ten random
      samples were based on herd code. Samples averaged 4926 dams and 2026 cytoplasmic
      lines. Model also included herd-year-seasons as fixed effects and genetic
      covariance for direct-maternal effects. Mean estimates of the effects of maternal
      genetic variances and direct-maternal covariances, as fractions of phenotypic
      variances, were 0.008 and 0.007 for milk yield, 0.010 and 0.010 for fat yield,
      and 0.006 and 0.025 for fat percentage, respectively. Average fractions of
      variance from cytoplasmic line were 0.011, 0.008, and 0.009 for milk yield, fat
      yield, and fat percentage. Removal of maternal genetic effects and covariance for
      maternal direct effects from the model increased the fraction of direct genetic
      variance by 0.014, 0.021, and 0.046 for milk yield, fat yield, and fat
      percentage; little change in the fraction was due to cytoplasmic line. Exclusion
      of cytoplasmic effects from the model increased the ratio of additive direct
      genetic variance to phenotypic variance by less than 2%. Similarly, when sire by
      herd interaction was excluded, the ratio of direct genetic variance to phenotypic
      variance increased 1% or less.

PMID- 9532510
TI  - Genetic evaluation for herd life in Canada.
AB  - Methods were developed for the national genetic evaluation of herd life for
      Canadian Holstein sires. The genetic evaluations incorporate information from
      survival (direct herd life) and information from conformation traits that are
      related to herd life (indirect herd life) after adjustment for production in
      first lactation to remove the effect of culling for production. Direct genetic
      evaluations for herd life were based on survival in each of the first three
      lactations, which was analyzed using a multiple-trait animal model. Sire
      evaluations thus obtained for survival in each of the first three lactations were
      combined based on their economic weights into an overall sire evaluation for
      direct herd life. Sire evaluations for indirect herd life were based on an index
      of sire evaluations for mammary system, feet and legs, rump, and capacity. A
      multiple-trait sire model based on multiple-trait across country evaluation
      methodology was used to combine direct and indirect genetic evaluations for herd
      life into an overall genetic evaluation for herd life. Sire evaluations for herd
      life were expressed in estimated transmitting ability as the number of lactations
      and represent expected differences among daughters in functional herd life
      (number of lactations); the average functional herd life was set equal to three
      lactations. Estimated transmitting abilities were normally distributed and ranged
      from 2.31 to 3.43 lactations.

PMID- 9532511
TI  - Minimum inhibitory concentrations for selected antimicrobial agents against
      organisms isolated from the mammary glands of dairy heifers in New Zealand and
      Denmark.
AB  - Minimum inhibitory concentrations were determined for selected antimicrobial
      agents against 872 bacteria isolated from intramammary infections in heifers in
      New Zealand (n = 401) and Denmark (n = 471). These values were reported in
      micrograms per milliliters. Antimicrobial agents tested against isolates from New
      Zealand were penicillin, cloxacillin, cephapirin, ceftiofur, novobiocin,
      enrofloxacin, erythromycin, and pirlimycin. The minimum inhibitory concentrations
      that inhibit 90% of the strains tested for these antimicrobial agents with
      Staphylococcus aureus were 4.0, 0.5, 0.5, 2.0, 1.0, 0.25, 0.5, and 1.0,
      respectively. The minimum inhibitory concentration values that inhibit 90% of the
      strains tested against the Staphylococcus spp. ranged from 0.5 to 1.0 for all
      antimicrobics. The minimum inhibitory concentrations against streptococci were <
      or = 0.06, 0.5, 0.13, 0.13, 4.0, 1.0, 0.13, and < or = 0.06, respectively.
      Antimicrobial agents tested against isolates from Denmark included penicillin,
      ampicillin, oxacillin, cephalothin, ceftiofur, penicillin plus novobiocin,
      erythromycin, and pirlimycin. Against S. aureus, the minimum inhibitory
      concentrations were 0.13, 0.5, 0.5, 0.5, 1.0, 0.25, 0.5, and 0.5, respectively.
      The minimum inhibitory concentrations against Staphylococcus spp. were 0.25,
      0.25, 0.5, 0.5, 1.0, < or = 0.06, 0.13, 1.0, and 0.5, respectively. The minimum
      inhibitory concentrations against the streptococci were < or = 0.06, 0.13, 0.5,
      0.5, 1.0, < or = 0.06, 0.13, 0.5, and 0.5, respectively. Minimum inhibitory
      concentration values for staphylococci from New Zealand and Denmark were similar
      to values reported for US isolates. Streptococci from New Zealand and Denmark had
      lower minimum inhibitory concentration values than did US isolates. Only
      ceftiofur and enrofloxacin were active against the Gram-negative bacilli.

PMID- 9532512
TI  - Evaluation of the utilization of dietary nitrogen by dairy cows based on urea
      concentration in milk.
AB  - The objective of this study was to determine whether milk urea concentration is a
      valuable tool to monitor the utilization of dietary N by dairy cows. Data from 11
      feed trials (n = 2828 observations of 356 cows) were used in this study. Dietary
      protein utilization was evaluated according to the Dutch DVE-OEB system. A close
      correlation (0.8) was found between rumen-degraded protein balance in the ration
      and urea concentration in milk. The effects of the balance of true protein
      digested in the small intestine and net energy on milk urea concentration were
      small but significant. Parity and stage of lactation did not significantly
      influence milk urea concentration. Because of the large variation among and
      within cows, the monitoring of protein utilization of an individual cow was
      inaccurate. However, milk urea concentration in bulk milk is a valuable tool to
      monitor the rumendegraded protein balance in the ration.

PMID- 9532513
TI  - Alteration in immune responsiveness during the peripartum period and its
      ramification on dairy cow and calf health.
AB  - Substantial evidence indicates that innate and acquired defense mechanisms are
      lowest from 3 wk precalving to 3 wk postcalving. This lowered responsiveness
      includes aspects of systemic and mammary gland immunity that may account, at
      least in part, for the increased incidence of peripartum disease. The physical
      and metabolic stresses of pregnancy, calving, and lactation may contribute to
      this decrease in host resistance and the subsequent increase in disease
      incidence. However, variation among cows in their host resistance mechanisms
      suggests that genotype and phenotype may possibly be used to identify cows that
      are able to mount beneficial immune responses over the periparturient period. Our
      own studies suggest that cows may be categorized as high or low responders based
      on the peripartum antibody responses to ovalbumin and Escherichia coli J5. Low
      responders were hyporesponsive to these test antigens and had a higher incidence
      of peripartum diseases, particularly mastitis. In many species, a functional link
      exists between the immune and endocrine systems, and, during periods of stress or
      physical injury, neuropeptides and neuroendocrine hormones function as
      immunomodulators. Initial investigations of peripartum cows reveal positive
      relationships between growth hormone kinetics and profiles of antibody response.
      Whether hormone fluctuations during the periparturient period are responsible for
      the alterations observed in immune responsiveness remains uncertain.

PMID- 9532514
TI  - Rationale and pharmacology of angiotensin II receptor antagonists: current status
      and future issues.
AB  - BACKGROUND: The renin-angiotensin system consists of a cascade of substrate
      enzyme interactions that culminates with the production of angiotensin II, the
      active peptide responsible for all the known effects of the renin-angiotensin
      system. Blocking this enzymatic cascade has been the focus of considerable
      research to the extent that the renin-angiotensin system is implicated in the
      control of blood pressure, sodium and water homeostasis, and cardiovascular
      function and structure. ANGIOTENSIN CONVERTING ENZYME INHIBITORS: Angiotensin
      converting enzyme (ACE) inhibitors provide one way of blocking the renin
      angiotensin system, and to this end the compounds have proved efficacious in the
      treatment of hypertension and cardiovascular disease. However, these compounds
      are limited in the extent to which they block the renin-angiotensin system,
      partly due to recently described alternate pathways for the genesis of
      angiotensin II and also because ACE is not a very specific enzyme and has
      multiple other potential substrates including bradykinin, tachykinins,
      neurotensin substance P, and others. ANGIOTENSIN II RECEPTORS: The development of
      angiotensin II receptor antagonists represents a new way to block the renin
      angiotensin system at the receptor level. Irbesartan is a new angiotensin II
      receptor antagonist that provides specific and insurmountable antagonism of the
      AT1 receptor subtype, demonstrating a greater than 8500-fold specificity for the
      AT1 receptor, the subtype which mediates all the known actions of angiotensin,
      compared to the AT2 receptor. Comparative studies have demonstrated that
      irbesartan is 10 times more potent than losartan and slightly more potent than
      E3174, losartan's active metabolite. Preclinical pharmacological studies in a
      variety of animal models have demonstrated that irbesartan provides a dose
      dependent, insurmountable blockade of angiotensin and reductions in blood
      pressure, urinary protein and glomerular sclerosis score.

PMID- 9532515
TI  - Non-insulin-dependent diabetes mellitus, nephropathy, and the renin system.
AB  - Renal protective effects in diabetic patients. Blocking the renin-angiotensin
      system slows the progression of nephropathy and end-stage renal disease in
      diabetes mellitus. While substantial evidence exists for the renal protective
      effects of angiotensin converting enzyme (ACE) inhibitors in patients with
      insulin-dependent diabetes mellitus (IDDM), the role of renin-angiotensin system
      blockade in non-insulin-dependent diabetes mellitus (NIDDM) is less clear. The
      evidence regarding ACE inhibitors has been attained through the traditional
      channels of evidence-based medicine: observational studies, trials in animal
      models, preliminary human analyses, and large, randomized trials. While a sound
      approach, these pathways to elucidating therapeutic effects require the
      expenditure of substantial time and resources. Accelerated trials with
      angiotensin II receptor antagonists have relied on the proven effects of ACE
      inhibitors in the diabetic patient, as well as on pharmacologic principles
      dictating that renin-angiotensin blockade is more complete when the system is
      interrupted at the rate-limiting or receptor level. Irbesartan and creatinine
      clearance in NIDDM patients. The Collaborative Study pilot trial has already
      shown that the angiotensin II receptor antagonist irbesartan is significantly
      more effective than the calcium antagonist amlodipine on creatinine clearance in
      hypertensive NIDDM patients. Subsequent to this trial, a large, randomized study
      of over 1600 hypertensive patients with NIDDM has been initiated. Other trials
      have indicated that the response to blocking angiotensin II receptors with
      irbesartan in patients with NIDDM is substantially larger than it is in healthy
      humans.

PMID- 9532516
TI  - Human pharmacokinetic/pharmacodynamic profile of irbesartan: a new potent
      angiotensin II receptor antagonist.
AB  - BACKGROUND: Inhibition of the renin-angiotensin system has been the focus of
      considerable research as the enzymatic pathway resulting in the production of
      angiotensin II is implicated in the development of hypertension and
      cardiovascular disease. ANGIOTENSIN CONVERTING ENZYME INHIBITORS: Blocking the
      renin-angiotensin system with angiotensin converting enzyme (ACE) inhibitors is
      an effective blood pressure control measure, but is less than ideal due to
      incomplete blockade and the effects of concomitant blockade of kinase II.
      ANGIOTENSIN II RECEPTOR ANTAGONISTS: Angiotensin II receptor antagonists block
      the renin-angiotensin system at the receptor level, and thus impede the system
      regardless of the pathway responsible for the formation of ACE. Irbesartan is a
      new, unique angiotensin II receptor antagonist with favorable
      pharmacokinetic/pharmacodynamic properties that are close to ideal for an
      antihypertensive agent. Irbesartan is a specific AT1 receptor antagonist with
      rapid oral bioavailability (peak plasma concentrations occurring at 1.5-2 h after
      administration) and a long half-life (11-15 h) that provides 24-h blood pressure
      control with a single daily dose. The maximal blood pressure fall occurs between
      3 and 6 h after the dose. Unlike other angiotensin II receptor antagonists,
      irbesartan is relatively unaffected by food or drugs. CONCLUSIONS: The
      pharmacokinetic/pharmacodynamic properties of irbesartan have been demonstrated
      to provide superior blood pressure control and tolerability in all classes of
      hypertension and patient populations.

PMID- 9532517
TI  - Twenty-four-hour ambulatory blood pressure evaluation of antihypertensive agents.
AB  - EVALUATION OF A SMOOTH BLOOD PRESSURE RESPONSE TO TREATMENT: Smooth or uniform
      blood pressure control is an obvious goal of antihypertensive therapy, but it is
      difficult to assess by the traditional clinic blood pressure measurements.
      Ambulatory blood pressure monitoring is therefore increasingly being used to
      evaluate new antihypertensive drugs and to assess the adequacy of treatment. The
      use of ambulatory blood pressure monitoring is based on two assumptions: that
      treatment must be continuously optimal, and that more frequent blood pressure
      measurements during treatment, particularly at different times and during various
      types of activity and mental states, may lead to a more accurate assessment than
      infrequent measurements in the clinic. When ambulatory blood pressure monitoring
      is used, the effect of a given antihypertensive agent or of a given
      antihypertensive regimen can be tested on the average blood pressure values over
      24 h, or on day- or night-time values. The actual verification of the achievement
      of a uniform reduction of blood pressure throughout the 24-h time span can be
      achieved by comparing 24-h blood pressure profiles before treatment and during
      treatment. The so-called trough: peak ratio is generally used in an attempt at a
      more quantitative assessment of smooth control. Recently, we have developed the
      Smoothness Index, defined as the ratio between the mean hourly change in blood
      pressure (calculated over the 24-h period), divided by the standard deviation of
      these hourly changes. We have some indication that this may be a more accurate
      measurement of smooth blood pressure control under therapy than trough: peak
      ratios. TWENTY-FOUR-HOUR BLOOD PRESSURE CONTROL BY IRBESARTAN: Ambulatory blood
      pressure assessments are important during the clinical testing of new
      antihypertensive agents. Our group recently performed a multicenter study to
      compare the anti-hypertensive effect of three irbesartan dose regimens (75 mg
      once a day, 150 mg once a day, 75 mg twice a day) and placebo as measured by 24-h
      ambulatory blood pressure monitoring and confirmed by office blood pressure
      measurements. All irbesartan regimens were significantly more effective than
      placebo. Irbesartan at 150 mg once a day provided clinically significant and
      sustained blood pressure reductions over a full 24 h and had the highest trough:
      peak ratio and Smoothness Index. No additional benefit was observed with twice
      daily dosing using irbesartan at 75 mg compared with a single daily at 150 mg.
      Therefore irbesartan at a single daily dose of 150 mg offers real efficacy with
      the potential for greater ease of administration compared with twice-daily
      antihypertensive therapy.

PMID- 9532518
TI  - Clinical overview of irbesartan: expanding the therapeutic window in
      hypertension.
AB  - BACKGROUND: The clinical management of hypertension has traditionally been
      hampered by a limited therapeutic window, which has resulted in the maintenance
      of patients on doses of antihypertensive agents that often produce clinically
      significant side effects and suboptimal blood pressure control. To expand this
      window, a therapeutic agent must provide optimal, dose-related blood pressure
      control with placebo-like tolerability. IRBESARTAN: Irbesartan, a new angiotensin
      II receptor antagonist, has been shown to provide significant blood pressure
      reductions compared with placebo and equal or better reductions compared with
      major antihypertensive agents of other classes. These effects have been
      demonstrated in an extensive clinical trials program, comprising 1691 irbesartan
      treated patients and 539 placebo-treated patients. Active-drug-controlled trials
      with beta-blockers, angiotensin converting enzyme inhibitors, calcium antagonists
      and diuretics have further confirmed the excellent results with irbesartan.
      Moreover, irbesartan demonstrates a clear dose-related therapeutic response with
      no dose-related effects on adverse event rates. CONCLUSIONS: The clear advantages
      of irbesartan over antihypertensive agents of other classes have the potential to
      expand the therapeutic window in the treatment of hypertension, thus improving
      the chances that a majority of patients will attain long-term blood pressure
      control with freedom from side effects.

PMID- 9532519
TI  - Stepped care for hypertension: are the assumptions valid?
AB  - OBJECTIVE: To examine whether the choice of initial antihypertensive medication
      is associated with patient withdrawal from therapy among a large cohort of newly
      diagnosed hypertensive individuals receiving medical care in actual practice.
      DESIGN: The records of the outpatient prescription drug plan of Saskatchewan,
      Canada, were searched for individuals with a diagnosis of essential hypertension
      who were receiving at least one antihypertensive drug between January 1989 and
      December 1994. Persistence was defined, and records were classified by class of
      initial antihypertensive agent prescribed. SUBJECTS: In all, the records of over
      79,000 individuals with a diagnosis of hypertension and an antihypertensive drug
      prescribed between 1990 and 1994 were evaluated. Persistence with therapy was
      considered in a subset of newly diagnosed patients, observed for at least 6
      months, and receiving an initial prescription from one of four major categories
      of antihypertensive agents. RESULTS: Among newly diagnosed patients, diuretics
      and angiotensin converting enzyme (ACE) inhibitors were the most common initial
      medication. ACE inhibitors were associated with the highest persistence rates
      after 1 year of follow-up (83%), followed by calcium antagonists (81%), diuretics
      (78%) and beta-blockers (74%) (P < 0.001). These results were unchanged in a Cox
      proportional hazards model which controlled for confounding by age, sex and proxy
      measures for prior health status. CONCLUSIONS: A significant proportion of newly
      diagnosed patients withdraw from therapy within the first year, and this
      withdrawal seems to be related to the choice of initial antihypertensive agent.
      These results suggest that recommendations for using stepped care in hypertension
      management may not be optimal if the initial agent prescribed is associated with
      decreased levels of persistence with therapy.

PMID- 9532520
TI  - Development of liposomal amphotericin B formulation.
AB  - A considerable effort has been spent in the past three decades to investigate
      various aspects of liposomes as novel drug delivery systems. In 1990, the first
      amphotericin B (AmB) liposomal preparation (L-AmB) under the brand name AmBisome
      was introduced into the market by Vestar. The successful marketing of the product
      moved liposomes out of the stage of experimental obscurity to the realistic stage
      of clinical utility. The launch of AmBisome sparked off the introduction of other
      lipid-based AmB products marketed by Liposome Technology (Amphocil) and The
      Liposome Co. (Abelcet). The drive behind the development of a modified
      formulation of AmB was to improve the therapeutic index of this drug with respect
      to its major drawback associated with both acute and chronic toxic effects. In a
      30-year-long experience with AmB, several reports were recorded in the literature
      of acute adverse effects, such as fever, rigors, vomiting, cardiotoxicity and
      hypotension occurring during infusion; while long-term therapy was reported to be
      associated with hypokalemia, renal dysfunction and hematological abnormalities.
      Another serious problem encountered with the drug had been the poor response
      obtained in immunocompromised patients like those with AIDS, neutropenia and
      cancer patients on chemotherapy. The encapsulation of amphotericin B in liposomal
      vesicles was hence targeted not only to obtain an improvement in the therapeutic
      index but also to see if it was useful in eradicating deep-seated fungal
      infections in immunocompromised patients. The liposomal AmB was found to have a
      better therapeutic index and lower toxicity than the commercial AmB preparations.
      The LD50 of AmBisome in mouse was 175 mg/kg compared with 3.7 mg/kg for
      Fungizone, the commercial preparation of AmB. Additionally, L-AmB has prolonged
      circulation time, and extravasates into the site of infection and delivers the
      drug directly to the site, with no nephrotoxicity and neurotoxicity as
      experienced with AmB. This review traces the course of development of L-AmB and
      discusses the rationale behind the development of its liposomal preparation. The
      results in in vitro, in vivo and clinical studies, mechanism of action,
      biodistribution, and formulation considerations of L-AmB are described. The
      clinical experience with the marketed preparation is reviewed.

PMID- 9532521
TI  - Development and in-vitro evaluation of sustained-release meclofenamic acid
      microspheres.
AB  - Meclofenamic acid (MFA) sustained-release microspheres were prepared by the
      solvent evaporation method using cellulose propionate (CP) polymer and acetone as
      the polymer solvent. Polyethylene glycol (PEG) was used as a channelling agent to
      improve the release properties of MFA at 1:2:1 drug to polymer to PEG ratio. The
      microspheres prepared at three different speeds (600, 800 and 1000 rpm) were
      characterized with regard to their surface morphology, average drug content,
      particle size distribution and release profiles in phosphate buffer, pH 8.0 at 37
      degrees C. The microspheres were stored under accelerated conditions for 3 months
      and the effect of storage on the different characteristics was studied. Spherical
      particles with essentially smooth surface and few residual drug crystals on the
      surface were formed. Smaller particles were formed at higher agitation speeds.
      The release rate of MFA from these microspheres was not affected by the molecular
      weight of CP polymer. PEG 2000 was found to have a more enhancing effect on the
      rate of the release than PEG 4000. The physical properties of the microspheres
      and their release characteristics were not altered by storing the product at 40
      degrees C/80% relative humidity (R.H.) for 3 months.

PMID- 9532522
TI  - Gelatin nanoencapsulation of protein/peptide drugs using an emulsifier-free
      emulsion method.
AB  - The nanoencapsulation of a model protein drug, bovine serum albumin (BSA), using
      gelatin as the matrix material is reported. Nanoencapsulation was conducted using
      a modified water-in-oil (w/o) emulsion method, which is emulsifier-free and
      simple. The nanoencapsulation product, BSA-containing gelatin nanoparticles, is
      characterized in terms of nanoparticle morphology, size and size distribution,
      water content, and in vitro protein release. The BSA-containing gelatin
      nanoparticles obtained from this nanoencapsulation process are nearly spherical
      and have a log-normal size distribution. The average diameter of the BSA
      containing gelatin nanoparticles is approximately 840 nm. They can absorb 51-72%
      of water. In vitro release experiments demonstrate that BSA has been successfully
      encapsulated in, and can be released from the gelatin nanoparticles. The release
      of BSA from the gelatin nanoparticulate matrix follows a diffusion-controlled
      release mechanism. It is found that temperature affects both the water content
      and the BSA release rate of the gelatin nanoparticles.

PMID- 9532523
TI  - Drug retention and stability of solid lipid nanoparticles containing
      azidothymidine palmitate after autoclaving, storage and lyophilization.
AB  - Solid lipid nanoparticles (SLNs) were prepared using trilaurine (TL) as the SLN
      core and phospholipid (PL) as coating. Neutral and negatively charged PLs were
      used to produce neutral and negatively charged SLNs. An ester prodrug of 3'-azido
      3'-deoxythymidine (Zidovudine, AZT), AZT palmitate (AZT-P), was synthesized and
      incorporated in the SLNs. The stability of SLN formulations containing AZT-P was
      studied at different temperatures. Drug retention and mean particle diameter of
      SLNs were determined after autoclaving, during temperature stability testing, and
      after lyophilization (with or without cryoprotective sugars) and reconstitution.
      There were no significant changes in the mean diameter and the zeta potential
      (zeta) of SLNs after autoclaving (121 degrees C for 20 min). The amount of
      incorporated AZT-P was, however, slightly reduced due to the formation of
      hydrosoluble AZT. Autoclaved SLNs were stable for a period of 10 weeks at 20
      degrees C but an increase in particle size and loss of AZT-P were observed at 4
      and 37 degrees C. Trehalose was an effective cryoprotectant for preventing SLN
      aggregation during lyophilization and subsequent reconstitution. Thermal
      gravimetric analysis showed that lyophilized preparations contained approximately
      1% water. Using appropriate trehalose to lipid ratios, AZT-P retention in the
      SLNs was 100% after reconstitution. Our results demonstrate that SLNs containing
      AZT-P can be autoclaved, lyophilized and reconstituted without significant
      changes in SLN diameter and zeta potential or in the quantity of incorporated
      prodrug.

PMID- 9532524
TI  - PDLLA microspheres containing steroids: spray-drying, o/w and w/o/w
      emulsifications as preparation methods.
AB  - Hydrocortisone and its more soluble ester, hydrocortisone 21-acetate, have been
      incorporated into poly(D,L-lactic) acid (PDLLA) microspheres using single, double
      emulsion/solvent evaporation and by spray-drying techniques. This paper describes
      the characterization of the microparticles obtained (morphology, particle size
      distribution, drug content, yield of production, in vitro drug release behaviour)
      and a comparison of the results (drug loading, drug release, size of the
      microspheres) obtained from the different techniques used. These results
      demonstrate that by using a relatively more soluble ester of an insoluble
      steroid, hydrocortisone, the drug content within the microspheres can be
      increased, together with a high efficiency of loading, irrespective of the
      technique employed. In the case of hydrocortisone, spray-drying produces the
      highest loading and encapsulation efficiency compared to both single and double
      emulsion methods for microspheres of similar size (about 2-4 microns) and
      suitable for lung delivery, but with lower yields (about 55% versus about 33%).

PMID- 9532525
TI  - Emulsion formulations of testosterone for nasal administration.
AB  - The nasal route has received a great deal of attention due to the many advantages
      of nasal delivery over parenteral administration. The male sex hormone
      testosterone is ineffective when administered orally due to its gut wall and
      first-pass metabolism. Therefore, an alternative method for delivery would be the
      intranasal route, if the lack of aqueous solubility can be overcome. In this
      study a new approach to emulsion formulations of the drug has been proposed based
      on the hypothesis that increased absorption is possible upon solubilization of
      the drug and/or prolongation of the formulation residence time in the nose. Three
      differently charged testosterone submicron size emulsion formulations with
      various zeta potentials (+24.8, -23.0 and 0.06 mV) were prepared as nasal spray
      formulations. A dose of approximately 3.8 mg testosterone per rabbit was
      administered to four rabbits and the bioavailability of the emulsion formulations
      was assessed and compared with an i.v. formulation via solid-phase extraction,
      followed by an HPLC analysis method. Statistical analysis of the normalized data
      indicated a bioavailability of 55, 51 and 37% for positively, negatively and
      neutrally charged emulsions respectively. The results of this study strongly
      suggest that emulsion formulations have some potential to be considered for nasal
      delivery. Further, both the positively and negatively charged emulsion
      formulations provided a better bioavailability than the neutral charged emulsion,
      probably indicating that the charged particle interactions between emulsion
      globules and the mucus layer prolong the contact of drug with nasal membrane thus
      enhancing drug absorption.

PMID- 9532526
TI  - Effect of bovine serum on the phase transition temperature of cholesterol
      containing liposomes.
AB  - The phase transition temperature of liposomes composed of
      dipalmitoylphosphatidylcholine (DPPC)/hydrogenated soy phosphatidylcholine (HSPC)
      at a 2:1 molar ratio was estimated in buffer, 30% and 50% bovine serum by
      monitoring the leakage of encapsulated self quenched doxorubicin (Dox) from the
      vesicles when exposed to a temperature increasing from 30-52 degrees C. The
      results showed that bovine serum caused a slight decrease in the phase transition
      temperature from 44 to 41 degrees C in 50% serum. Addition of 50% cholesterol to
      this liposomal composition resulted in the disappearance of transition
      temperature in buffer and 30% serum, whereas 50% bovine serum resulted in the
      reappearance of the transition temperature at 46 degrees C. The data suggest that
      bovine serum affects the transition temperature of liposomes in a concentration
      dependent manner, and this effect is more pronounced in cholesterol-rich
      liposomes. The time course for the release of Dox from both kinds of liposomes
      (cholesterol rich and cholesterol free) during incubation in 50% bovine serum, at
      temperatures close to the transition temperature (42 degrees, 45 degrees C), was
      followed. The results showed an increased leakage of Dox from both kinds of
      liposomes, at both temperatures. However, liposomes with high cholesterol content
      released more drug at 42 degrees than at 45 degrees C. The size of these
      liposomes was monitored in 10% bovine serum at 25 degrees C for a period of 1 h
      using photon correlation spectroscopy. The data showed no variation in the size
      of both cholesterol-rich and cholesterol-free liposomes for this period, which
      indicates that bovine serum does not affect the size of either cholesterol-rich
      or cholesterol-free liposomes.

PMID- 9532527
TI  - Ionotropic gelation: encapsulation of indomethacin in calcium alginate gel discs.
AB  - Ionotropic gelation by divalent metal interaction was employed as an approach to
      design a modified release multiple-unit oral drug-delivery system. This process
      was achieved by crosslinking an indomethacin-sodium alginate dispersion with
      calcium ions to induce the spontaneous formation of indomethacin-calcium alginate
      gel discs. A significant part in the validation of the integrity of the system,
      involved a preformulatory stage for the optimization of the curing conditions and
      potency determination of the gel discs. A three-phase approach was developed to
      establish the critical curing parameters. Since curing involved crosslinking of
      the sodium alginate with calcium ions, an optimal concentration of calcium
      chloride (phase one) and crosslinking reaction-time (phase two) had to be
      determined. Furthermore, the third phase involved the optimization of the air
      drying time of the gel discs. In phases one and two, stabilization of in vitro
      drug-release characteristics was used as the marker of optimal crosslinking
      efficiency. Phase three was based on achieving fully dried gel discs by drying to
      constant weight at 21 degrees C under an extractor. The study revealed that
      optimal crosslinking efficiency was achieved in 1%w/v calcium chloride solution
      for 24 h and air-dried at 21 degrees C under an extractor for 48 h. The three
      solvent/solution systems investigated for their ability to liberate completely
      the drug from the matrix system were methanol, sodium citrate (1%w/v) and
      phosphate buffer pH 6.2. Phosphate buffer provided optimal drug removal, in
      addition to its ability to induce swelling of the calcium alginate gel discs.
      Furthermore, drug loading also increased with the use of increasing
      concentrations of sodium alginate in the formulations.

PMID- 9532529
TI  - Fluid-bed microencapsulation of ascorbic acid.
AB  - Ascorbic acid has been fluidized and microencapsulated with three different
      hydrophobic coating materials by the top-spray method. The experiments were
      conducted with polymethacrylate coating material formulated as a water
      dispersion, and ethyl-cellulose and waxy coating material both formulated as
      organic solutions. Characteristics of the fluidized bed procedure in conical
      geometry have been determined by estimation of two parameters: bed porosity and
      total pressure drop. A satisfactory agreement between experimental and calculated
      values has been reached. The following properties of the microencapsulated
      ascorbic acid have been determined: core content, bulk and tapped density,
      crystal size distribution prior and after microencapsulation, surface morphology
      and release profile. The comparison and evaluation of different hydrophobic
      coating materials have been performed on the basis of these findings.

PMID- 9532528
TI  - Preparation of silicone microspheres by emulsion polymerization: application to
      the encapsulation of a hydrophilic drug.
AB  - The objective of this work was to evaluate the ability of appropriate silicone
      elastomers to encapsulate hydrophilic compounds in microspheres prepared
      according to a multiphase emulsion-polymerization process. The particle size of
      the microspheres can be modified by controlling the usual emulsification
      parameters, such as the viscosity of the different phases, shear rates and
      surface activity properties of additives. The encapsulation efficiencies of a
      hydrophilic drug, propranolol hydrochloride, were very high but its release rates
      were very slow. Osmotic agents such as glycerol and propylene glycol did not
      enhance the release rate, whereas it was slightly increased by both sodium
      chloride addition and higher drug loading.

PMID- 9532530
TI  - Ocular neuromyotonia: three case reports with eye movement recordings.
AB  - The objective of this article was to evaluate the etiologies, findings, and
      treatment of ocular neuromyotonia (ONM) in three case reports. The etiologies of
      ONM were determined by the histories, neuroradiologic tests, or biopsies.
      Clinical observations, videotaping, and electronic eye movement recordings
      documented the eye movement abnormalities. Intermittent diplopia developed
      several years after myelography with thorium dioxide (Thorotrast), radiation
      treatment for a pituitary tumor, and radiotherapy for medulloblastoma of the
      posterior fossa. All of the patients had intermittent, variable tropias that
      occurred spontaneously or were induced by eccentric gaze. One patient had a
      partial third nerve palsy, and another had a unilateral internuclear
      ophthalmoplegia (INO). ONM involved the paretic third nerve, extraocular muscles,
      and ipsilateral lateral rectus muscle in one patient, the paretic medial rectus
      muscle (INO) in one patient, a lateral rectus muscle (INO) in one patient, and a
      lateral rectus muscle in the last patient. Eye movement recordings were
      consistent with spasms of the involved muscles. Carbamazepine (Tegretol)
      abolished the ONM in two patients. The other patient had been taking
      carbamazepine for seizures and developed ONM when the dose was decreased.
      Increasing the dose abolished the ONM. ONM is an unusual cause of intermittent
      diplopia and strabismus, but its distinctive history and signs identify it
      easily. Damage to the peripheral cranial nerves might produce segmental
      demyelination, axonal hyperexcitability, and a self-perpetuating, reverberating
      circuit that causes spasms of the extraocular muscles.

PMID- 9532531
TI  - Foveal cone dysfunction syndrome.
AB  - Our objective was to describe and expand the clinical spectrum of a rarely
      detected, previously reported photoreceptor disorder restricted to the foveal
      cones. Three patients with bilaterally decreased acuity and hemeralopia were
      examined to exclude a structural, vascular, inflammatory, or degenerative
      process. Each patient underwent a full neuroophthalmic examination, including
      full-field and focal cone electroretinogram (ERG). All three patients had normal
      appearing fundi, mild dyschromatopsia, central or paracentral visual field
      depressions, normal full-field photopic and scotopic ERGs, and markedly reduced
      focal, foveal cone ERG responses. One patient had a ring scotoma and an
      asymptomatic family member with abnormal full-field and focal cone ERG. The
      syndrome of acquired foveal cone dysfunction presents as a bilateral, painless,
      progressive central visual loss with minimal or absent fundus changes. It eludes
      diagnosis until focal, foveal cone ERG is performed.

PMID- 9532532
TI  - Occult maculopathy and the focal ERG.

PMID- 9532533
TI  - The treatment of periocular and facial pain with topical capsaicin.
AB  - This article describes the effects of topically applied capsaicin (a nociceptive
      substance-P suppressor) in patients with neuropathic periocular or facial pain.
      Peripheral neuropathic pain is a major cause of periocular or facial discomfort
      and usually follows injury to a subcutaneous peripheral nerve. Though the damage
      is local, the pain tends to radiate. We studied three patients who complained of
      a 2- to 30-year history of fluctuating pain in the periocular area. All three had
      an area of point tenderness that responded to the topical application of
      capsaicin cream.

PMID- 9532534
TI  - Follow-up studies on pattern reversal visually evoked cortical potentials in a 2
      year-old child with optic neuritis.
AB  - A 2-year and 7-month-old boy had sudden visual loss in both eyes and showed
      bilateral optic neuritis without systemic symptoms. Steroid therapy improved his
      visual acuity from 0.077 and 0.053 to 1.0 at 7 months after onset. Magnetic
      resonance imaging (MRI) of the brain showed high density in both optic nerves and
      multiple lesions in the white matter that were enhanced by gadolinium. We
      considered the diagnosis of demyelinating disease. Follow-up MRI showed no
      abnormal lesion. Both transient and steady-state pattern visually evoked cortical
      potentials were nondetectable at the onset, and the P100 component of the
      transient pattern reversed visually evoked cortical potential appeared to be
      delayed thereafter. It has since become shorter in parallel with visual acuity
      improvement.

PMID- 9532535
TI  - Steroid-responsive HIV optic neuropathy.
AB  - A 37-year-old man with bilateral optic neuropathy who recovered on steroid
      treatment is described. He was subsequently found to be human immunodeficiency
      virus 1 (HIV-1) positive prior to the onset of his visual symptoms, and no other
      cause of his optic neuropathy could be found. There is some evidence that HIV
      itself may be a cause of symptomatic optic neuropathy. A spontaneously relapsing
      and remitting multiple sclerosis-like syndrome has previously been described in
      HIV-positive patients, and this may present with optic neuritis. A chronic optic
      neuritis in HIV-positive patients that is not usually symptomatically important
      has also been described. We review the literature related to these topics and our
      patient.

PMID- 9532536
TI  - Late-onset Leber's hereditary optic neuropathy.
AB  - Progressive, sequential visual loss in the left and then right eye was reported
      in a 73-year-old male over three months. The presence of a family history of
      visual loss and the lack of other findings in association with bilateral
      cecocentral scotomata led to a diagnosis of new onset Leber's hereditary optic
      neuropathy, confirmed by the presence of a mutation at the 11,778 position. This
      case illustrates that Leber's hereditary optic neuropathy may manifest late in
      life.

PMID- 9532537
TI  - Presumed bilateral occipital neurosarcoidosis. A case report.
AB  - A 37-year-old man with a history of sarcoidosis, hypertension, asthma, depression
      and prior intravenous drug use presented with complaints of difficulty in finding
      his way around the house, headache, and blurred vision in both eyes. The symptoms
      had been increasing in severity over the prior several months. Physical
      examination showed normal visual acuity, pupil reactions, and fundi but severe,
      circumferential constriction of the visual fields bilaterally. The visual fields
      enlarged appropriately on increasing the distance from the patient to the tangent
      screen. Neuroimaging revealed bilateral, occipital meningeal involvement and
      parenchymal lesions consistent with sarcoidosis. Treatment with oral
      corticosteroids produced a mild subjective improvement in the patient's symptoms
      and stabilized the visual fields, without improving them. This case represents an
      unusual presentation of presumed neurosarcoidosis involving the visual pathways
      at the level of the occipital lobes.

PMID- 9532538
TI  - A new clinical technique for demonstrating changes in eye acceleration during
      horizontal saccades in patients with partial internuclear ophthalmoplegias.
AB  - The eyelid-mounted accelerometer can pick up the acceleration waveform of the eye
      during horizontal eye movements. The acceleration profile comprises high
      amplitude pulsatile activity in the saccade and changes in the level of
      background ocular microtremor related to eye position. Adducting saccades of 20
      degrees were recorded in eight patients with partial internuclear
      ophthalmoplegias caused by multiple sclerosis and in eight age-matched healthy
      subjects. The initial pulse of acceleration activity was reduced by 85% in the
      patients. In the worst-affected cases, adducting saccades were associated only
      with an increase in the level of background ocular microtremor in the
      acceleration trace. The results confirm the hypothesis that an internuclear
      ophthalmoplegia is due to the loss of the pulse signal to ocular motor neurons,
      with preservation of the step signal in an adducting saccade.

PMID- 9532539
TI  - Ocular tilt reaction with vertical eye movement palsy caused by localized
      unilateral midbrain lesion.
AB  - A 60-year-old man developed diplopia and experienced difficulty moving his eyes.
      Vertical movement of each eye, including vestibulo-ocular reflex and smooth
      pursuit, was extremely limited. Horizontal eye movements were normal. His head
      position was tilted toward his left. There was 10 prism diopters of exotropia and
      10 prism diopters of right hypertropia. Fundus photographs revealed a clockwise
      torsion of both eyes. These signs indicate leftward ocular tilt reaction.
      Magnetic resonance imaging showed a small area of an increased signal intensity
      localized in the midbrain dorsomedial to the red nucleus on the right side. Based
      on recent experimental evidence, it may be assumed that the unilateral lesion
      involving the right interstitial nucleus of Cajal most probably caused leftward
      ocular tilt reaction in our patient.

PMID- 9532540
TI  - Saccadic ping-pong gaze.
AB  - Ping-pong gaze (PPG), or short-cycle periodic alternating gaze, consists of
      horizontal conjugate ocular deviations alternating every few seconds. This
      alternating gaze has been described as appearing to be smooth. However, our
      electrooculographic study of four consecutive unconscious patients with PPG
      showed smooth waveforms in one patient but saccadic cog-wheeling in three
      patients. In one of the three patients with saccadic PPG, a transition from
      smooth to saccadic waveforms was noted with clinical improvement. Whereas the
      patient with smooth PPG died immediately, the patients with saccadic PPG survived
      in a persistent vegetative state. These findings suggest that saccadic PPG is a
      clinical variant of PPG in patients in a lighter state of consciousness, possibly
      related to less extensive brain damage.

PMID- 9532541
TI  - Terminating attacks of ocular neuromyotonia.
AB  - We examined a 30-year-old woman who, for 6 months, had suffered from ocular
      neuromyotonia, which consisted of episodic ocular depression. Apart from the
      ocular complaint, her medical history and the clinical findings were
      unremarkable. The patient discovered that she could terminate each episode of
      tonic ocular depression instantly by forcefully directing her gaze upward.
      Stretching the affected muscle might also prove to be an effective way of ending
      attacks of neuromyotonia in other patients suffering from this condition.

PMID- 9532542
TI  - Papilledema in a man with an "occult" dural arteriovenous malformation.

PMID- 9532543
TI  - Pseudotumor cerebri sine papilledema with unilateral sixth nerve palsy.
AB  - A 17-year-old woman presented with a history of 1-week of headache and 3 days of
      horizontal diplopia. Examination revealed 20/20 vision in both eyes, no
      papilledema, and an abduction deficit in her left eye. Lumbar puncture revealed
      an opening pressure of 440 mm H2O. After treatment with acetazolamide, the
      headache and abduction deficit resolved. Papilledema never developed. This is a
      unique case of pseudotumor cerebri sine papilledema with a unilateral abduction
      deficit. We suggest that young women with headache and unilateral abduction
      deficits may be unrecognized cases of pseudotumor cerebri.

PMID- 9532544
TI  - Bilateral anterior ischemic optic neuropathy following influenza vaccination.
AB  - Optic neuritis is an occasional complication of vaccination. Visual loss can be
      unilateral or bilateral, and most patients recover substantially without
      treatment. The presumptive mechanism is an immune-mediated demyelinating injury
      of the optic nerve. We report two patients who had permanent visual loss
      following influenza vaccination. Their pattern of visual loss, segmental optic
      disc changes, and failure of visual recovery were atypical for demyelinating
      optic neuritis and reminiscent of a primary ischemic injury to the optic nerve.
      We speculate that an immune complex-mediated vasculopathy following vaccination
      can cause anterior ischemic optic neuropathy. Clinicians should be aware of this
      entity because of the less favorable prognosis for visual recovery in these
      cases.

PMID- 9532545
TI  - Optic nerve head swelling in the Hadju-Cheney syndrome.
AB  - The Hadju-Cheney syndrome is one of the idiopathic acroosteolyses. Associated
      neurologic abnormalities are often a result of progressive basilar invagination.
      A 48-year-old man with the Hadju-Cheney syndrome developed progressive bilateral
      visual loss. On examination, he had hyperopia, choroidal folds, optic nerve head
      swelling, and mild optic neuropathy. Computed tomographic scans showed massive
      enlargement of both intraorbital optic nerve sheaths. Improvement occurred after
      optic nerve sheath fenestration. Visual loss due to optic nerve meningocele can
      occur in the Hadju-Cheney syndrome. Optic nerve sheath fenestration can result in
      visual improvement. It is unclear whether the occurrence of optic nerve
      meningocele is causally or fortuitously related to the Hadju-Cheney syndrome.

PMID- 9532546
TI  - Annual review of systemic diseases: 1995-1996. Part I.
AB  - Systemic illnesses, such as vasculitides and systemic lupus erythematosus, may
      have ocular symptoms, or they may present with ocular signs and undiagnosed or
      occult systemic signs. The recently described ophthalmic and neurologic
      presentations and new diagnostic modalities for Wegener's granulomatosis, giant
      cell arteritis, and systemic lupus erythematosus are reviewed. Hypercoagulable
      states and their role in visual diseases are assessed, and strategies for
      evaluating patients with hypercoagulable states are described.

PMID- 9532547
TI  - Quality-of-life studies: organ transplantation research as an exemplar of past
      progress and future directions.

PMID- 9532548
TI  - Designing clinical trials for the treatment of medically unexplained physical
      symptoms.

PMID- 9532549
TI  - A randomized, double-blind crossover trial of sertraline in women with chronic
      pelvic pain.
AB  - The efficacy of antidepressants as analgesics for a range of chronic pain
      problems is well documented. However, a controlled trial of an antidepressant for
      women with chronic pelvic pain has not yet been published. We randomized 23 women
      from a general gynecology clinic to either double-blind sertraline or placebo.
      Measures of psychological function, pain, and functional disability were taken at
      baseline and 6 weeks. After a 2-week washout, the groups were crossed-over and
      the same measures were done over the next 6 weeks. There were no significant
      improvements in pain or functional disability noted on sertraline compared to
      placebo. Studies involving larger samples of patients are needed to confirm these
      findings.

PMID- 9532550
TI  - The generalizability of cardiovascular responses across settings.
AB  - The generalizability of cardiovascular reactivity change scores remains largely
      unsupported. In previous studies, several factors differed between laboratory and
      field, making poor lab-to-life correlations difficult to interpret. The present
      study varied only one parameter between the lab and field: setting. In this
      study, 24 females were studied on four occasions: twice in the lab (to provide
      test-retest reliability); once in a classroom; and once at home. After a
      baseline, subjects performed a math task, while blood pressure and heart rate
      were monitored. Procedures were identical in all sessions. Blood pressure changes
      were fairly reliable between the two lab sessions, with rs values 0.68 (systolic)
      and 0.62 (diastolic pressure); however, lab/nonlab correlations were lower (0.47
      for SBP; 0.38 for DBP). This suggests that even a minor variation in procedure,
      such as a change in setting, can affect generalizability; other lab-field
      differences may have an even greater impact.

PMID- 9532551
TI  - Disease severity, physical limitations and depression in HIV-infected men.
AB  - Previous research has failed to identify a consistent relationship between HIV
      disease severity and depression. However, HIV/AIDS can lead to substantial
      physical limitations in those with advanced disease, which may influence mood.
      This study examined the extent to which HIV disease severity and physical
      limitations were associated with depressive symptoms in 49 HIV-infected men at
      the final stages of a 5-year prospective study. No differences were found in
      depression or quality of life among men who were asymptomatic, symptomatic, or
      diagnosed with AIDS. Forty-three percent of subjects reported substantial
      physical limitations, which were associated with higher depression scores and
      poorer quality of life. Degree of physical limitation predicted depression
      concurrently as well as depression 6 months later, after controlling for disease
      stage, physical symptoms, and CD4 cell counts. Findings suggest that physical
      limitations are more important than laboratory markers of disease progression in
      understanding psychological adjustment to illness in HIV-infected men.

PMID- 9532552
TI  - Psychophysiological reactivity in pediatric migraine patients and healthy
      controls.
AB  - The hypothesis that physiological responses of migraine patients are symptom
      specific was evaluated in 29 children (age range 8-16 years) suffering from
      migraine and 10 healthy control children. The assessment included two major
      stress phases and a relaxation period. A standard laboratory stressor (a
      subtraction task) and parent-child conflict served as stressors. A total of six
      physiological parameters were measured: pulse amplitude at two extracranial (A.
      temporalis, A. supraorbitalis) and one peripheral (index finger) sites; finger
      temperature; heart rate; and skin-conductance level. There were no significant
      group differences in autonomic arousal. Moreover, extracranial and peripheral
      vasomotor activity was not different between groups, a finding which might be
      partially due to the considerable interindividual variability. The implications
      of the results are discussed taking into account that studying pediatric rather
      than adult migraine patients allows to minimize the potentially confounding
      impact of factors such as headache chronicity, medication, and additional
      nonmigraine headaches.

PMID- 9532553
TI  - Five-year follow-up for adverse outcomes in males with at least minimally
      positive angiograms: importance of "denial" in assessing psychosocial risk
      factors.
AB  - The purpose of this study was to test the role of "denial" (spouse/friend minus
      self-ratings on parallel versions of the same questionnaire) in diluting the
      predictive value of emotional distress for cardiac events (deaths, new MIs,
      and/or revascularizations). One hundred forty-four men with no history of prior
      revascularization who had at least minimally positive diagnostic coronary
      angiograms, and someone they selected as "someone who knows you well," completed
      parallel versions of the Ketterer Stress Symptom Frequency Checklist (KSSFC).
      They were followed up by phone an average of 59.7 months after recruitment.
      Length of follow-up, baseline cardiac risk factors, and a number of baseline
      obtained psychosocial risk factors were tested as prospective predictors of
      combined events (death by any cause, new MIs, and/or revascularizations) and
      current anginal frequency. Only spouse/friend observed anxiety on the KSSFC
      predicted current anginal frequency (p = 0.001). On the self-report version of
      the KSSFC, patients with one or more events reported less anger (p = 0.031),
      depression (p = 0.008), and anxiety (p = 0.003). These results may be
      attributable to "denial" because there were no differences in spouse/friend
      ratings, and difference scores (spouse/friend minus patient) on the KSSFC scales,
      particularly anger, were also related to events: AIAI (p = 0.002); depression (p
      = 0.063); and anxiety (p = 0.010). Denial may be a major limiting factor in
      accurately assessing emotional distress in cardiac populations, and may help
      account for a number of the previous findings.

PMID- 9532554
TI  - Attentional control of pain perception: the role of hypochondriasis.
AB  - The role of hypochondriasis in the attentional control of pain perception was
      investigated in 28 in-patients (12 women and 16 men) at a hospital for
      psychosomatic disorders, who had been classified into high- and low
      hypochondriacal categories by means of the Illness Attitude Scales (IAS). The two
      groups did not differ in their basic pain sensitivity based on their heat pain
      thresholds. Attentional control was manipulated by a mental arithmetic task,
      resulting in one experimental condition with distraction and one without
      distraction. In both of the conditions, subjects rated the intensity and the
      unpleasantness of nonpainful and painful heat stimuli on visual analog scales
      (VAS). Distraction significantly reduced the perceived intensity and
      unpleasantness of the stimuli at painful levels but not at nonpainful levels.
      Contrary to our expectation, the individual level of hypochondriasis did not
      influence this result. Although distraction seemed to have a strong influence on
      pain perception, hypochondriasis as a symptom or a trait did not contribute to
      this effect.

PMID- 9532555
TI  - Hostility and adrenergic receptor responsiveness: evidence of reduced beta
      receptor responsiveness in high hostile men.
AB  - We examined the relation of Cook and Medley Hostility (Ho) scores to alpha- and
      beta-adrenergic receptor responsiveness to pharmacological agonists in 22
      normotensive and 14 hypertensives (aged 18-34) white males, matched for age and
      body mass. alpha-Adrenergic receptor responsiveness was measured by the
      phenylephrine dose required to increase mean blood pressure by 25 mmHg (PD25).
      beta-Adrenergic responsiveness was measured by the isoproterenol dose needed to
      increase heart rate by 25 bpm (CD25), and to lower systemic vascular resistance
      by 40% (VD40). Relative to men with low Ho scores (< or = 21), men with high Ho
      scores (> or = 21) showed significantly reduced vascular beta 2-adrenergic
      receptor responsiveness (VD40). Moreover, the decreased vascular responsiveness
      was more pronounced in borderline hypertensive men with high Ho scores. Ho scores
      were also marginally significant in predicting cardiac beta 1- and beta 2
      adrenergic receptor responsiveness, such that men with high Ho scores showed
      decreased responsiveness as indexed by a larger CD25. Vascular alpha 1-adrenergic
      responsiveness was not associated with hostility. These observations suggest that
      hostility, alone or in conjunction with BP status, is associated with reduced
      cardiovascular beta-adrenergic receptor responsiveness.

PMID- 9532556
TI  - Poor concentration and the ability to process information after glandular fever.
AB  - The symptom of poor concentration and the ability to process information were
      measured prospectively in 245 subjects three times in the 6 months after
      glandular fever or an ordinary upper respiratory tract infection. The effects of
      the different infections, having a fatigue state, a psychiatric disorder, sleep
      disturbance, and estimates of premorbid intelligence were also assessed. The most
      frequent complaint of poor concentration and the worst information processing
      occurred at the onset of the infection, but these problems decreased over time,
      and were not related to each other. Multiple regression modeling showed that
      higher socioeconomic class and vocabulary IQ were associated with information
      processing ability at all three interviews. In contrast, logistic regression
      modeling showed that the symptom of poor concentration was associated with the
      severity of general psychiatric morbidity (CIS score) followed by suffering from
      a fatigue state. These results suggest that the ability to process information
      after these particular infections is related to estimates of premorbid IQ,
      whereas poor concentration is related independently to both psychiatric morbidity
      and a fatigue state, but not the particular infection itself.

PMID- 9532557
TI  - The value of screening for psychiatric disorders prior to upper endoscopy.
AB  - Gastrointestinal (GI) complaints are among the most common symptoms in primary
      care yet are frequently unexplained and often lead to costly diagnostic testing.
      We sought to determine the prevalence of psychiatric disorders in patients with
      unexplained GI complaints undergoing upper endoscopy, and the likelihood of
      endoscopic abnormalities in patients with and without psychiatric diagnoses. We
      prospectively evaluated 116 adult patients who were undergoing upper endoscopy to
      evaluate GI complaints. All subjects received a structured psychiatric interview
      prior to endoscopy using PRIME-MD, and endoscopists were blinded to the PRIME-MD
      results. Psychiatric disorders were detected in 70 (60%) patients. Overall, there
      were 113 diagnoses (some patients had multiple disorders) with the most common
      being somatoform (44%), depressive (29%), and anxiety (19%) disorders. Only 29
      patients had major endoscopic abnormalities, including esophageal disease (14),
      peptic ulcer (9), severe gastritis (4), gastric cancer (1), and esophageal cancer
      (1). There was a much higher prevalence of psychiatric disorders in patients
      without major endoscopic abnormalities (74% vs. 21%, p < 0.0001). Psychiatric
      disease was strongly predictive of endoscopic findings (OR for major abnormality
      = 0.11 in women, and 0.40 in men), especially if somatoform disorder was present
      (OR = 0.15). We conclude that, with a simple questionnaire, psychiatric disorders
      can be diagnosed in a large proportion of patients with unexplained GI complaints
      who are referred for upper endoscopy. The presence of a psychiatric disorder,
      particularly if somatoform, makes it unlikely that endoscopy will reveal
      significant GI disease.

PMID- 9532558
TI  - Retroviral vectors.

PMID- 9532559
TI  - Adenoviral vectors.

PMID- 9532560
TI  - Herpes simplex virus vectors.

PMID- 9532561
TI  - Liposome-mediated gene transfer.

PMID- 9532562
TI  - Intramuscular injection of plasmid DNA.

PMID- 9532563
TI  - Yeast artificial chromosome vectors.

PMID- 9532564
TI  - Gene transfer and cancer chemotherapy.

PMID- 9532565
TI  - Vaccine immunotherapy for cancer.

PMID- 9532566
TI  - Inherited immunodeficiencies.

PMID- 9532567
TI  - Anti-viral strategies.

PMID- 9532568
TI  - AIDS and HIV infection.

PMID- 9532569
TI  - Cystic fibrosis and lung diseases.

PMID- 9532570
TI  - Arthritis.

PMID- 9532571
TI  - Duchenne muscular dystrophy.

PMID- 9532572
TI  - Cardiovascular disease.

PMID- 9532573
TI  - Degenerative and inherited neurological disorders.

PMID- 9532574
TI  - Mucopolysaccharidosis.

PMID- 9532575
TI  - DNA-based immunization.
AB  - Over the past 2 years the principle of nucleic acid immunization has been
      demonstrated in several different animal models. Each of these was based on
      direct gene transfer using plasmid DNA into one or more tissues, with skeletal
      muscle being the preferred target. The expression vectors used to date have
      encoded antigens from several different viruses as well as a tumor-specific
      protein, an MHC class I molecule and a parasite antigen. It is clear that the
      induction of a broad range of immune responses is possible with DNA-based
      immunization, including the ability to confer protection against viral or
      parasitic challenge. In some cases, the immune response is superior to that
      obtained with traditional recombinant protein vaccination. For example, in the
      case of hepatitis B surface antigen, antibody appears earlier and levels rise
      more quickly with DNA-based than with recombinant protein vaccination (Davis et
      al., 1994). Despite the very promising beginning of this new approach, many
      issues remain to be examined before application to humans, especially those
      concerned with safety. In the meantime however, DNA-based immunization offers an
      extremely powerful tool for molecular immunologists to study the immune system
      and with which to develop new vaccines and other immunotherapeutic approaches.
      One can easily and rapidly clone and modify genes in plasmid DNA expression
      vectors, allowing many new constructs to be produced and tested in a short period
      of time which can be on the order of weeks. In contrast, the preparation of viral
      vectors, or the production and purification of recombinant proteins from
      bacteria, yeast or stably transfected mammalian cell lines, can easily take
      months to develop. The DNA-mediated induction of an immune response to a protein
      produced in situ has therefore initiated a new era of vaccine research. There is
      now the possibility to dramatically modify the way one approaches prophylactic
      vaccination, and as a consequence public health care can potentially be improved
      in a highly cost-effective manner.

PMID- 9532576
TI  - Ontogeny of gene expression of Kir channel subunits in the rat.
AB  - We report the detailed gene expression of all subunits within the Kir2 and Kir3
      inwardly rectifying K+ channel subfamilies in the developing rat. Using in situ
      hybridization, onset of expression and cellular distribution of transcripts in
      embryonic and postnatal rat brains as well as in peripheral tissues is evaluated.
      Beginning at embryonic day 13 (E13), except "forebrain" Kir2.3 subunits which are
      absent from the body and brain until E21, all subunits appear with distinct and
      mainly nonoverlapping expression patterns. During ontogenic development,
      expression in the CNS becomes more widespread, leading to widely overlapping mRNA
      patterns as observed in the adult rat. Subunits are mainly found in regions of
      the developing brain that are also positive in the adult. Most subunits, in
      particular Kir3.2 and Kir3.4, are expressed transiently in distinct brain nuclei
      during ontogeny. Appearance of Kir transcripts is not generally related to the
      progressive and recessive phases during neurogenesis, but rather regulated
      differentially for each subunit and any specific group of neurons. It is
      demonstrated for the first time that several subunits, and most abundantly
      Kir2.2, are present early in the peripheral nervous system, i.e., in dorsal root
      , sensory cranial-, and sympathetic ganglia. Also, of all subunits Kir3.3 is
      ubiquitously expressed in the entire embryonic nervous system and throughout the
      body. In summary, analysis of ontogenic Kir channel expression helps deciphering
      the importance of Kir channels (as exemplified for the defective weaver Kir3.2
      gene) during proliferation, differentiation, and synaptogenesis in the CNS.

PMID- 9532577
TI  - Differential distribution of agrin isoforms in the developing and adult avian
      retina.
AB  - At the developing and regenerating neuromuscular junction, agrin is responsible
      for the formation of aggregates containing the acetylcholine receptor (AChR) and
      other molecules. Multiple isoforms of agrin are generated by alternative
      splicing, and the presence of an 8, 11, or 19 (8 + 11) amino acid insert at
      splice site B is required for agrin's AChR aggregation activity. An antiserum was
      generated against the 19 amino acid peptide which reacted specifically with the
      B11 and B19 agrin isoforms. The antiserum blocked the formation of agrin-induced
      AChR aggregates on myotubes, but the peptide itself had no aggregation activity,
      suggesting that agrin's active site is close to the splice site, but not the
      peptide itself. In the embryonic and adult retina anti-peptide immunoreactivity
      was concentrated in the synapse-containing layers. In contrast, the inner
      limiting membrane and radial cells, which express strong immunoreactivity with a
      pan-specific anti-agrin antiserum, were not stained by the anti-peptide
      antiserum, showing that agrin isoforms are differentially distributed in the
      retina. In addition, agrin B11 and B19 isoforms were associated with ganglion
      cell axons, particular at early developmental stages before synapse formation,
      indicating additional functions for these isoforms in the developing CNS.

PMID- 9532578
TI  - NGF binding to p75 enhances the sensitivity of sensory and sympathetic neurons to
      NGF at different stages of development.
AB  - To clarify the role of the common neurotrophin receptor p75 in modulating the
      survival response of sensory and sympathetic neurons to NGF at different stages
      of development, we compared the actions of wild-type NGF with a mutated NGF
      protein that binds normally to TrkA, the NGF receptor tyrosine kinase, but has
      greatly reduced binding to p75. At saturating concentrations, the NGF mutant
      promoted the survival of similar numbers of trigeminal sensory and sympathetic
      neurons as NGF. At subsaturating concentrations, the NGF mutant was less
      effective than wild-type NGF in promoting the survival of embryonic sensory
      neurons and postnatal sympathetic neurons but was equally effective as wild-type
      NGF in promoting the survival of embryonic sympathetic neurons. Whereas the
      levels of trkA and p75 were similar in embryonic sensory neurons and postnatal
      sympathetic neurons, the level of p75 was significantly lower than that of trkA
      in embryonic sympathetic neurons. These results indicate that binding of NGF to
      p75 enhances the sensitivity of NGF-dependent neurons to NGF at stages in their
      development when the levels of p75 and TrkA are similar.

PMID- 9532579
TI  - Neurotrophins differentially regulate voltage-gated ion channels.
AB  - Neurotrophic factors profoundly affect neuronal differentiation, but whether they
      influence neuronal phenotype in instructive ways remains unclear: do different
      neurotrophic factors always trigger identical programs of differentiation or can
      each impose distinct functional properties even when acting upon the same
      population of target neurons? We addressed this issue by examining the regulatory
      effects of the four neurotrophins on the molecular components of electrical
      excitability, voltage-gated ion channels, within a single cellular context. Using
      patch clamp methods, we studied neurotrophin regulation of voltage-gated sodium,
      calcium, and potassium currents in SK-N-SH neuroblastoma cells. We found that
      each neurotrophin induced a unique pattern of expression of ionic currents
      despite similar activation of initial signal transduction events. Thus, each
      neurotrophin imposed a different excitable phenotype even when acting upon the
      same target cells.

PMID- 9532580
TI  - Neuregulin expression in PNS neurons: isoforms and regulation by target
      interactions.
AB  - Neuregulins have several important functions in the development of the peripheral
      nervous system, acting on both developing Schwann cells and muscle fibers. To
      determine whether these factors are also important for peripheral nerve
      regeneration, we have analyzed neuregulin expression in motor and sensory neurons
      by Northern blots and in situ hybridization. The results of this analysis show
      that the predominant neuregulin isoform expressed in these neurons is a novel
      transmembrane splice variant. After axotomy, there is a rapid decline in
      neuregulin expression in both motor and sensory neurons, but following
      reinnervation of target tissues, neuregulin expression returns to near normal
      levels. These results indicate that the normal expression of neuregulins in these
      neurons is maintained by the interactions with target tissues.

PMID- 9532581
TI  - Regulation of expression of the sensory neuron-specific sodium channel SNS in
      inflammatory and neuropathic pain.
AB  - Increased voltage-gated sodium channel activity may contribute to the
      hyperexcitability of sensory neurons in inflammatory and neuropathic pain states.
      We examined the levels of the transcript encoding the tetrodotoxin-resistant
      sodium channel SNS in dorsal root ganglion neurons in a range of inflammatory and
      neuropathic pain models in the rat. Local Freund's adjuvant or systemic nerve
      growth factor-induced inflammation did not substantially alter the total levels
      of SNS mRNA. When NGF-treated adult rat DRG neurons in vitro were compared with
      NGF-depleted control neurons, SNS total mRNA levels and the levels of membrane
      associated immunoreactive SNS showed a small increase (17 and 25%, respectively),
      while CGRP levels increased fourfold. SNS expression is thus little dependent on
      NGF even though SNS transcript levels dropped by more than 60% 7-14 days after
      axotomy. In the streptozotocin diabetic rat SNS levels fell 25%, while in several
      manipulations of the L5/6 tight nerve ligation rat neuropathic pain model, SNS
      levels fell 40-80% in rat strains that are either susceptible or relatively
      resistant to the development of allodynia. Increased expression of SNS mRNA is
      thus unlikely to underlie sensory neuron hyperexcitability associated with
      inflammation, while lowered SNS transcript levels are associated with peripheral
      nerve damage.

PMID- 9532583
TI  - Cerebrospinal fluid markers in multiple sclerosis: an overview.
AB  - Cerebrospinal fluid (CSF), with its protein markers, is a formidable material for
      investigating the relationships among the various cell types involved during the
      initial phase of plaque formation, or, successively, in the remyelination
      process. Its analysis may give definite help in better focusing on therapeutic
      objectives and therapeutic tools. Therefore, the possible use of CSF MBP, S-100,
      GFAP, N-CAM, NGF, and CNTF in pathogenetic studies and in clinical follow-up is
      critically reviewed. The need for correct interpretation of the data, for
      uniformity and reliability of the analytical methods, and for easy access to them
      is stressed. CSF examination and MRI should not be considered as alternative
      tools, or in competition, but should be used together, to take the maximum
      advantage of their individual possibilities.

PMID- 9532582
TI  - SHARPs: mammalian enhancer-of-split- and hairy-related proteins coupled to
      neuronal stimulation.
AB  - In the mammalian central nervous system, a diverse group of basic helix-loop
      helix (bHLH) proteins is involved in the determination of progenitor cells and,
      subsequently, in regulating neuronal differentiation. Here we report the
      identification of a novel subfamily of bHLH proteins, defined by two mammalian
      enhancer-of-split- and hairy-related proteins, termed SHARP-1 and SHARP-2. In
      contrast to known bHLH genes, detectable transcription of SHARP genes begins at
      the end of embryonic development marking differentiated neurons that have reached
      a final position, and increases as postnatal development proceeds. In the adult,
      SHARP genes are expressed in subregions of the CNS that have been associated with
      adult plasticity. In PC12 cells, a model system to study neurite outgrowth, SHARP
      genes can be induced by NGF with the kinetics of an immediate-early gene.
      Similarly, within 1 h after the administration of kalnic acid in vivo, SHARP-2 is
      induced in neurons throughout the rat cerebral cortex. This suggests that
      neuronal bHLH proteins are also involved in the "adaptive" changes of mature CNS
      neurons which are coupled to glutamatergic stimulation.

PMID- 9532584
TI  - Protein markers of brain damage.
AB  - Brain proteins are released into body fluids in a fashion which reflects the
      underlying pathogenetic mechanisms for individual diseases. It is therefore
      important to distinguish not only different protein markers (reflecting various
      brain cells from which they have been released), but also their metabolism at
      different sites within the body (e.g. reticulo-endothelial system vs renal
      clearance) which will have an important bearing on whether fragments of the
      protein are found in urine or blood. It is clear that different patterns of
      protein abnormalities would be helpful in differential diagnosis of the
      individual diseases which afflict the nervous system. It would also be useful to
      monitor these proteins either as surrogate markers of the natural history of the
      condition or in the various therapies for each disease.

PMID- 9532585
TI  - Multiple sclerosis: IL-2 and sIL-2R levels in cerebrospinal fluid and serum.
      Review of literature and critical analysis of ELISA pitfalls.
AB  - The presence of interleukin-2 (IL-2) and soluble IL-2 receptors (sIL-2R) in the
      serum and cerebrospinal fluid (CSF) of patients suffering from multiple sclerosis
      (MS) has been extensively investigated. These studies, however, have produced
      conflicting results. The only significant finding concerns the frequent detection
      of increased sIL-2R levels in the serum in patients with relapsing-remitting MS
      (RRMS), especially after a short interval of time from the last relapse. Whether
      this finding can be used for clinical purposes requires further investigation. A
      standardization of the ELISA methods used to detect cytokines in biological
      fluids is urgently needed. Increased serum and/or CSF levels of IL-2 and sIL-2R
      strongly confirm a CD4+ Th1 activation.

PMID- 9532586
TI  - The cytokine storm in multiple sclerosis.
AB  - MS is associated with a cytokine storm characterized by the parallel upregulation
      of proinflammatory (IFN-gamma, TNF-alpha, and beta, and IL-12) and immune
      response-down-regulating (TGF-beta, IL-10) cytokines. Also IL-6 and the cytolytic
      molecule perforin are upregulated. Even when evaluated in individual MS patients
      over the disease course, no Th1/Th2 dichotomy is obvious but, instead,
      upregulation of Th1 + Th2 + Th3 cytokines simultaneously, probably reflecting the
      complex pathology of MS in lesion size, time and distribution in the individual
      patient. Few correlations have been observed between cytokines and clinical MS
      variables, though upregulation of TGF-beta seems to correlate with benign course
      and minor disability. Both pro- and antiinflammatory cytokines are also produced
      by microglia and astrocytes, constituting a CNS-cytokine network that interacts
      with the cytokine network of the immune system. This complexity is to be kept in
      mind when searching for cytokine abnormalities in MS.

PMID- 9532587
TI  - Myelin basic protein in cerebrospinal fluid and other body fluids.
AB  - Myelin basic protein (MBP) or a fragment thereof may enter cerebrospinal fluid
      (CSF) and other body fluids in an etiologically nonspecific fashion to provide
      information about the status of central nervous system (CNS) myelin damage. MBP
      immunochemically detected is referred to as MBP-like material (MBPLM). The
      clinical utility of the assay for MBPLM in CSF is to document the presence,
      continuation, or resolution of CNS myelin injury. The analysis of CSF for MBPLM
      is subject to many variables, among which are the antisera and the form of the
      assay utilized. The dominant epitope of CSF MBPLM is in the decapeptide of 80-89
      from the intact MBP molecule of 170 residues. Normally, CSF has no detected
      MBPLM. Following an acute relapse of MS, MBPLM rises quickly in the range of
      ng/ml and rapidly declines and disappears. The presence of MBPLM in CSF in
      chronic and progressive phases of the disease is unusual, but it may sometimes be
      detected in low levels, depending on the assay used for detection. The level of
      CSF MBPLM is related to both the mass of CNS myelin damage and how recently it
      occurred. The level of CSF MBPLM rarely is elevated in optic neuritis. The level
      of CSF MBPLM is unrelated to CSF protein level, level of IgG, presence of
      oligoclonal bands or pleocytosis. CSF MBPLM has the potential of serving as a
      marker of therapeutic effectiveness in MS and does have predictive value for
      response to glucocorticoids given for worsening of disease. The detection of
      MBPLM in body fluids other than CSF would be of great value because of the
      resulting improved feasibility for objectively monitoring the natural history of
      MS and response to therapy. Studies on blood have yet to produce a valid assay of
      MBPLM. Urinary MBPLM, though different in its features from that in CSF, may
      provide a correlate, not with acute demyelination in MS as is the case for CSF,
      but with progression of disease.

PMID- 9532588
TI  - Intrathecal synthesis of virus-specific oligoclonal IgG, and of free kappa and
      free lambda oligoclonal bands in acute monosymptomatic optic neuritis. Comparison
      with brain MRI.
AB  - Twenty-seven patients with acute monosymptomatic optic neuritis were randomly
      selected from a population-based cohort of patients extensively screened for
      known etiologies of ON. Paired serum and CSF obtained median 20 days from onset
      were examined for oligoclonal IgG, free kappa and free lambda chains, and virus
      specific oligoclonal IgG antibodies by an affinity-mediated capillary blot
      technique. CSF-restricted oligoclonal IgG bands, free kappa and free lambda chain
      bands were observed in 17, 15 and nine patients, respectively. In addition, 16
      patients showed a polyspecific intrathecal synthesis of oligoclonal IgG
      antibodies against one or more viruses (12 measles, nine varicella zoster, six
      rubella, six mumps) compared to all the 18 examined patients with definite
      multiple sclerosis (P = 0.0014). The presence of virus-specific oligoclonal IgG
      was significantly related to the results of oligoclonal IgG (P = 0.0034), free
      kappa chain bands (P = 0.0020), and brain MRI abnormalities (P = 0.0402). At 1
      year follow-up five patients had developed clinically definite multiple
      sclerosis; all had virus-specific oligoclonal IgG antibodies, oligoclonal IgG and
      abnormal MRI at onset.

PMID- 9532589
TI  - Cerebrospinal fluid and serum nitric oxide metabolites in patients with multiple
      sclerosis.
AB  - Nitric oxide is hypothesised to play a role in the immunopathogenesis of multiple
      sclerosis. Raised cerebrospinal fluid and serum levels of the nitric oxide
      metabolites nitrate and nitrite have been described in patients with multiple
      sclerosis. Cerebrospinal fluid and serum nitrate and nitrite were measured in
      patients with multiple sclerosis, inflammatory and non-inflammatory neurological
      diseases, and correlated with the albumin quotient, an index of blood-brain
      barrier dysfunction. Patients undergoing diagnostic lumbar and vene puncture were
      prospectively recruited, clinical data were obtained from the hospital records,
      and the CSF and serum nitrate and nitrite levels were measured by the nitrate
      reductase and Griess reaction methods. Nitrate and nitrite, were raised in the
      CSF and serum of patients with multiple sclerosis and other inflammatory
      neurological diseases compared to patients with non-inflammatory neurological
      disorders (median nitrate and nitrite: cerebrospinal fluid = 10.3 microM vs 15.4
      microM vs 6.6 microM, P < 0.001, and serum = 49.0 microM vs 46.4 microM vs 38.8
      microM, P = 0.02, respectively). CSF nitrate and nitrite levels correlated with
      the albumin quotient (n = 59, r = 0.42, P < 0.001). This study provides further
      evidence for a role of nitric oxide in the immunopathogenesis of multiple
      sclerosis and supports a role for nitric oxide as a possible mediator of
      inflammatory blood-brain-barrier dysfunction.

PMID- 9532591
TI  - Abnormalities of biogenic amines affecting the metabolism of serotonin and
      catecholamines.
AB  - This paper describes the relevance of measuring biogenic amine metabolites in
      cerebrospinal fluid in order to detect inborn errors affecting catecholamines and
      serotonin biosynthesis. Defects in tetrahydrobiopterin and a deficiency of
      aromatic L-amino acid decarboxylase, tyrosine hydroxylase or dopamine-beta
      hydroxylase are candidate inborn errors for neurotransmitter metabolites
      screening. This investigation has to be considered in any child with motor
      retardation and extrapyramidal signs.

PMID- 9532590
TI  - Identification of peptides binding to IgG in the CSF of multiple sclerosis
      patients.
AB  - Phage displayed random peptide libraries were screened in order to identify
      phagotopes reacting with the IgG present in the cerebrospinal fluid (CSF) of
      multiple sclerosis (MS) patients. Six families of phagotopes each composed of
      different isolates were identified. These phagotopes were used as reagents, to
      characterise IgG present in the CSF of MS patients. The following results were
      obtained: (a) CSF antibodies from different patients display different
      specificities; (b) anti-phagotope antibodies are also present in the serum of MS
      patients; (c) Anti-phagotope antibodies are equally frequent in the serum of MS
      patients and of healthy individuals; (d) some of the anti-phagotope antibodies
      are enriched in the CSF of MS patients. These data show that the natural
      antigen(s) recognised by CSF antibodies is rather common in the general
      population. By using the selected phagotopes as immunogens in rabbits, we have
      derived large quantities of anti-phagotope antisera which can provide for useful
      tools toward the identification of the natural antigen(s) recognised by MS CSF
      antibodies.

PMID- 9532592
TI  - Soluble intercellular adhesion molecule-I (sICAM-I) in serum and cerebrospinal
      fluid of demyelinating diseases of the central and peripheral nervous system.
AB  - Serum and cerebrospinal fluid (CSF) soluble intercellular adhesion molecule-I
      (ICAM-I) levels were evaluated (ELISA) in 22 untreated and 13 corticosteroid
      treated active relapsing remitting (RR) Multiple Sclerosis (MS), in 10 untreated
      and 10 corticosteroid-treated Guillain-Barre syndrome (GBS) and in 17 non
      inflammatory neurological diseases (NIND). Twenty-eight clinically inactive RR MS
      were assayed for serum sICAM-I before and after 3 months treatment of 8 MIU rIFN
      beta-Ib taken s.c. every other day. High sICAM-I serum levels above the NIND
      values were found in untreated clinically active MS and in untreated GBS (P <
      0.05) but not in the untreated clinically inactive MS group. The active MS group
      showed significantly (P = 0.0001) higher sICAM-I serum levels if compared to the
      inactive group. Corticosteroid-treated active MS and GBS patients showed lower (P
      < 0.05) serum sICAM-I levels than the corresponding untreated groups. Serum sICAM
      I levels after 3 months of rIFN beta-Ib treatment (P < 0.0001, paired t-test)
      resulted increased compared to pretreatment values in MS. The mean values of
      CSF/serum sICAM-I:CSF/serum Albumin ratios (sICAM-I Index) in active untreated MS
      patients were higher compared to NIND (P < 0.005) and to corticosteroid-treated
      MS group (P = 0.01). sICAM Index values in GBS did not differ from those in NIND.
      The results seem to suggest potential roles for serum sICAM-I in downregulating
      the ongoing inflammatory response at the blood-brain barrier level and for CSF
      sICAM-I in the maintenance of a central nervous system local immune response.

PMID- 9532593
TI  - AAPS focus groups: a promising mechanism for scientific interchange.

PMID- 9532594
TI  - The release mechanism of an oral controlled-release delivery system for
      indomethacin.
AB  - This study was carried out to fully characterize the release kinetics of an oral
      controlled-release tablet formulation of indomethacin with xanthan gum. Matrix
      swelling, matrix erosion, and drug diffusion studies were performed to elucidate
      the operative release mechanisms of a tablet compressed from a ternary mixture of
      indomethacin-xanthan gum-lactose. Drug release tests were performed according to
      the USP paddle method in phosphate buffer pH 7.4, concurrently with the
      dissolution of the gum. Mean dissolution time (MDT) of the drug was calculated
      from the release profile and it was used as a parameter to evaluate the influence
      of (a) polymer content in the dosage form, (b) ionic strength of the medium, and
      (c) the rotation speed of the paddle on the release characteristics of the drug.
      There is a linear relationship between MDT and the inverse of polymer content.
      Within the range of ionic strength of the gastrointestinal tract, the salt
      concentration of the dissolution medium has a negative (inhibitory) effect on
      release rate of the drug and on matrix swelling. A positive (enhancing) influence
      of the salt concentration on drug diffusion in the hydrated matrices was noted.
      The polymer dissolution follows almost immediately the dissolution of the drug. A
      linear relationship between MDT and the inverse of paddle rotation speed has been
      observed. Swelling-controlled erosional process is the operative mechanism for
      indomethacin release from xanthan gum matrices.

PMID- 9532595
TI  - Comparison of the performance of two sample thieves for the determination of the
      content uniformity of a powder blend.
AB  - The objective of this study was to compare the performance of two sample thieves
      (plug and grain) to determine the content uniformity of a powder blend. The
      powder blend was prepared by mixing 2% drug substance with the remaining
      excipients in a tumble blender for 30 min. Samples were taken at 10 locations in
      the blender using both thieves. The performance of each sample thief was assessed
      based on the respective content uniformity values and relative standard
      deviations obtained for each device, as well as the content uniformity values
      reported following analysis of the resulting compressed tablets. The relative
      standard deviation values for blend samples taken with the plug thief were
      approximately half of those obtained using the grain thief. The superior
      performance of the plug thief in this study is attributed to the static charge
      acquired by the microcrystalline cellulose, which leads to poor flow
      characteristics. This impeded the flow of the blend into the sample chamber of
      the grain thief resulting in segregation and variable content uniformity results.
      The plug thief, which does not require powder flow to obtain a sample, performs
      better for this formulation. The selection of a sampling thief should be assessed
      on a case-by-case basis. Superior performance is expected for the plug thief when
      poor flowing, compressible blends are sampled.

PMID- 9532596
TI  - Modified Young's modulus of microcrystalline cellulose tablets and the directed
      continuum percolation model.
AB  - The purpose of this investigation was to analyze the modified Young's modulus of
      microcrystalline cellulose tablets at comparatively low relative densities, based
      on concepts of percolation theory. Tablets were prepared and tested using a Zwick
      1478 universal testing instrument. For statistical evaluation a new method is
      introduced for power laws, which exhibits highly correlated model parameters.
      According to our results the model Leuenberger, Leu is consistent with an
      Effective Medium Approximation which exhibits an exponent equal to one far away
      from the percolation threshold. In addition, the results show that it is
      essential to evaluate the elastic behavior of tablets close to the percolation
      threshold. For the different types of MCC a critical exponent q = 3.95 +/- 0.14
      was obtained. This result is very essential, as it is in good agreement with the
      theoretically expected value of 3.9 from an elastic network (central force
      model). The proposed model describes the modified Young's modulus better than
      former model equations taking into account the relative density. Thus, the
      process during uniaxial compaction can be imagined as a directed continuum
      percolation and the relative density of compacts can be identified as a space
      occupation probability density phi yielding reasonable percolation thresholds.

PMID- 9532597
TI  - Influence of protein emulsifier interfacial properties on oil-in-water emulsion
      stability.
AB  - The purpose of this study was to determine whether the interfacial properties of
      emulsifier films could be related to emulsion stability and therefore be used as
      stability predictors using Bovine serum albumin (BSA) as a model oil-in water
      (o/w) emulsifier. Soybean o/w emulsions were prepared by ultrasonication,
      emulsion droplet interfacial charge was determined by microelectrophoresis,
      droplet size distribution was measured using an Accusizer, and centrifugal stress
      was studied using an ultracentrifuge. Real time, thermal kinetic, and centrifugal
      stress accelerated stability tests were performed. Stability data obtained from
      centrifugal stress tests followed the same trends as real time stability data and
      these data were in general agreement with stability predictions made based on
      interfacial properties. The thermal kinetic accelerated tests were not predictive
      of stability, because emulsion breakdown was rapid and did not allow
      differentiation between the emulsions. Emulsion stability increased with an
      increase in emulsifier concentration (emulsions prepared at 2% w/v BSA had not
      cracked at 60 days, whereas those prepared at 0.1% w/v had cracked-by 30 days),
      increase in ionic strength (emulsions prepared at an ionic strength of 1 mM had
      cracked by 60 days, whereas those prepared at an ionic strength of 10 mM had
      cracked by 90 days), and decrease in temperature (emulsions prepared at 37 and 60
      degrees C had cracked by 5 days, whereas those prepared at 5 and 25 degrees C had
      not cracked at 60 days). There was no significant change in stability for
      emulsions prepared at pH 5.3 and pH 7.4. The addition of dextran sulfate improved
      emulsion stability, whereas the addition of acacia decreased stability. Emulsions
      prepared with BSA alone cracked by 90 days, those prepared with BSA and acacia
      cracked by 30 days, and those prepared with BSA and dextran sulfate had not
      cracked at 90 days. Interfacial properties were useful in predicting emulsion
      stability.

PMID- 9532598
TI  - Effect of relative humidity during tabletting on matrix formation of
      hydrocolloids: densification behavior of cellulose ethers.
AB  - The aim of this research was to investigate the elastic-plastic deformation
      behavior of the cellulose ethers hydroxypropylmethylcellulose (HPMC),
      hydroxyethylmethylcellulose (HEMC), and sodium carboxymethylcellulose (NaCMC) at
      relative humidities (RH) of 38, 57, and 75% and assess how the release of drugs
      embedded in such matrices is affected by the inner structure of the tablets
      formed during tabletting. Sorption and desorption isotherms and glass transition
      temperature were determined between 32 and 75% RH. The materials were
      equilibrated at 38, 57, and 75% RH and tabletted to a range of graded maximum
      relative densities. Pressure-time and displacement-time curves were analyzed by
      use of the Heckel function and a modified Weibull function (pressure-time only).
      After equilibration at the different RHs, all materials were in the glassy state.
      The respective degrees of polymerization had negligible effect on the absolute
      content of water, the sorption isotherms, and finally the densification behavior.
      At 38% RH, NaCMC contains the same amount of water as HPMC and HEMC, but deforms
      less plastically than the latter. This is attributed to tight binding of the
      water of hydration in the former. With increasing RH, NaCMC becomes only a little
      more plastic than both HPMC and HEMC, although it contains more than twice the
      amount of water. The binding strength of water and its molecular mobility, not
      the amount, seems to determine the readiness for volume reduction under load.

PMID- 9532599
TI  - Thermodynamics of propylparaben/beta-cyclodextrin inclusion complexes.
AB  - The aim of this study was to develop models for rigorous analysis of phase
      solubility diagrams, particularly the descending portion, in order to obtain
      individual thermodynamic complex formation and solubility product constants.
      Additionally, the effect of varying the initial solute concentration St, in
      excess of the optimal solubility Sm, on the general shape of the plateau and
      descending portions of the solubility diagram was investigated. The solubilities
      of propylpapraben (Seq) were measured against initial beta-cyclodextrin
      concentrations (Lt) at different temperatures and different St. Equilibrium
      concentrations (Leq) were also measured. The only effect observed was a
      broadening of the plateau region with increase in St with no discernible effect
      on Sm. Simultaneous rigorous analysis of the rising as well as the descending
      portions of the phase diagram could only be interpreted in terms of formation of
      two soluble complexes: SL and S2L. Rigorous analysis of the descending portion
      allowed the determination of individual formation constants K11 (SL) and K21
      (S2L) in addition to the solubility product of the less soluble complex KS11
      (SL). Thermodynamic analysis of the individual solubility of propylparaben and
      beta-cyclodextrin was carried out in water at different temperatures. In aqueous
      beta-cyclodextrin solutions, however, the solubility of propylparaben is enhanced
      due to the formation of both SL (delta G11(0) = -26.4 kJ/mol) and S2L (delta
      G21(0) = -46.4 kJ/mol) soluble complexes. Formation of the SL-complex is favored
      both by enthalpy (delta H11(0) = -20.7 kJ/mol) and a slight increase in entropy
      (delta S11(0) = 18.6 J/mol.K). Formation of S2L from SL apparently involves
      stronger solute-SL binding (delta H21(0) = -45.9 kJ/mol) yet is retarded by a net
      decrease in entropy (delta S21(0) = -86.3 J/mol.K). The solubility of the SL
      complex is highly endothermic (delta HS11(0) = 55.8 kJ/mol), and although is
      accompanied by much randomization (delta SS11(0) = 101.8 J/mol.K), its solubility
      remains quite low (delta GS11(0) = 25.5 kJ/mol). Molecular mechanical modeling of
      propylparaben/beta-cyclodextrin interactions in water revealed that the S2L
      complex formation is energetically more favored.

PMID- 9532600
TI  - In vitro release of colchicine using poly(phosphazenes): the development of
      delivery systems for musculoskeletal use.
AB  - A colchicine release system utilizing biodegradable poly(phosphazenes) was
      investigated in vitro for intra-articular administration. Polymer degradation and
      drug release studies were performed on colchicine-loaded poly(phosphazenes)
      containing either imidazolyl (I-PPHOS) or ethyl glycinato (EG-PPHOS) side chain
      substituents over a 21-day period. To study the effects of an implantable
      colchicine-PPHOS delivery system on local musculoskeletal tissue in vitro,
      osteoblast-like cells were grown on the matrices. Colchicine release was 20% for
      I-PPHOS and 60% for EG-PPHOS over the 21-day period. Release appeared to proceed
      through a combination of diffusional and degradative mechanisms. Environmental
      scanning electron microscopy (ESEM) studies revealed large pores in the drug
      depleted devices in contrast to the control matrices without drug, which may have
      contributed to the release seen, especially with ethyl glycinato-containing
      matrices. Cell growth on matrices containing colchicine was significantly (p <
      0.05) inhibited in contrast to growth on tissue culture polystyrene (TCPS) and EG
      PPHOS matrices without drug. The in vitro cell kinetic data suggest that designs
      for in vivo studies must take into account possible toxicity of colchicine and
      the polymer matrix on local tissue. Biodegradable PPHOS systems are promising
      candidates for use as intra-articular delivery vehicles for drugs with potential
      for systemic toxicity.

PMID- 9532601
TI  - Estimation of the amount of water removed by gap and atomization air streams
      during pelletization in a rotary processor.
AB  - The purpose of this study was to estimate the amount of water removed by the gap
      and atomization air streams during pelletization by the wet granulation technique
      in a rotary processor and to test the hypothesis that the influence of the water
      addition rate on the pellet size (1,7) mainly originates from differences in the
      amount of water removed by these air streams. Estimations from flow, temperature,
      and relative humidity measurements of the air streams, and estimations from
      moisture content measurements, indicated that approximately 3.6 g of water/min
      was removed during spheronization. The estimations from the air streams'
      characteristics obtained for the water loss during the water addition phase (2.6
      g/min) reflected the water removal during the later stages and did not reflect
      the overall rate of water removal during the total water addition phase as
      estimated from moisture content measurements (2.0 g/min). This was attributed to
      the fact that estimations from the air streams' characteristics could not take
      into account the early stages of the water addition phase. In these early stages,
      the amount of water removed was very limited. Using the foregoing estimations,
      differences in amount of water removed by the air streams could be compensated by
      adding more water when the water addition rate was decreased. This resulted in
      similar pellet sizes (geometric mean diameter of 800-850 microns) using different
      water addition rates. Thus, the hypothesis that the major influence of the water
      addition rate on the pellet size mainly originates from differences in the amount
      of water removed by the gap and atomization air streams was confirmed.

PMID- 9532602
TI  - Buoyancy and drug release patterns of floating minitablets containing piretanide
      and atenolol as model drugs.
AB  - The purpose of this study was to evaluate factors for improving the in vitro
      buoyancy and the drug release characteristics of floating minitablets containing
      either piretanide or atenolol as model drugs. The buoyancy of the minitablets was
      achieved either by the swelling of the excipient or by incorporation of the gas
      generating agent sodium bicarbonate. Resultant-weight kinetics were performed in
      order to evaluate the buoyancy. The release rate of the poorly soluble drug
      piretanide was enhanced by increasing its solubility or by promoting the erosion
      of the minitablets. For the sparingly soluble drug atenolol, the minitablets were
      coated with different ratio of insoluble polymer in order to diminish the release
      rate of this drug. The swelling of a hydrophilic excipient was not sufficient to
      obtain floating minitablets. The buoyancy of the minitablets containing either
      piretanide or atenolol was greatly improved by adding sodium bicarbonate as well
      as by a wet granulation. The most satisfactory improvement in the release rate of
      piretanide was achieved using a solid dispersion with povidone, thus increasing
      the drug solubility concomitantly with the increase of the minitablets' erosion.
      Regarding atenolol, minitablets containing 7% sodium bicarbonate and coated with
      Eudragit NE30D:RS 70:30 gave satisfactory results concerning buoyancy and drug
      release rate. This study showed that it was possible to produce minitablets
      containing either piretanide or atenolol, which have a positive resultant-weight
      during more than 6 hr and satisfactory release profiles.

PMID- 9532603
TI  - Evaluation of the hydrophobic drug loading characteristics in nanoprecipitated
      amphiphilic cyclodextrin nanospheres.
AB  - The aim of this work was to evaluate the loading capacity and the association
      characteristics of the hydrophobic drug progesterone on amphiphilic cyclodextrin
      nanospheres prepared by the nanoprecipitation method. The colloidal suspensions
      were prepared in the presence or absence of two different surfactants, Pluronic
      F68 and Tween 80. The physicochemical characteristics of the nanospheres were
      assessed using a nanosizer, zetameter, and transmission electron microscope. The
      physical state of the drug was verified using differential scanning calorimetry
      (DSC) and x-ray diffraction (XRD) methods. The in vitro progesterone release was
      investigated at 37 degrees C after dilution of the suspensions in sink
      conditions. Nanospheres with a mean diameter from 100 to 300 nm and a low degree
      of polydispersity were prepared from amphiphilic hexanoyl-gamma-cyclodextrin. The
      progesterone loading capacity was not affected by the formulation parameters
      tested. The DSC and XRD studies demonstrated the absence of the crystalline
      domains of progesterone in loaded nanospheres. The DSC studies also demonstrated
      the presence of interactions between the drug and carrier. The release of the
      drug from the carrier was extremely rapid and was governed by a partition
      phenomenon that depends only on the solubility of the drug in the release medium.
      From these results, we concluded that with this method, the progesterone is
      molecularly associated at the surface of the cyclodextrin nanospheres, probably
      through hydrophobic interactions in specific sites. The release profiles obtained
      can be of value when an improvement in the bioavailability of the drug is
      desired.

PMID- 9532604
TI  - Evaluation of extended-release applications for solid dispersion hot-melt fluid
      bed coatings utilizing hydrophobic coating agents.
AB  - A new hot-melt fluid bed coating method was evaluated for potential extended
      release applications. Chlorpheniramine maleate (CPM) USP was chosen as a model
      drug. The assays for drug release and content uniformity were dictated by the USP
      Official Monograph for a Chlorpheniramine Maleate Extended-Release Capsule. The
      fluid bed chamber was charged with CPM-loaded nonpareils and hydrophobic coating
      agents in the solid state. The method consists of four processing stages: (a)
      warming, (b) preheating, (c) melting-spreading, and (d) cooling-congealing.
      Various hydrophobic coating agent candidates were evaluated for extended-release
      potential by a preliminary screen at a coating agent level of 1.5% (w/w). A
      beeswax coating agent was identified as the most promising candidate of the
      preliminary screen. After the level of beeswax was increased to 2.0%, the
      dissolution profile met all of the specifications of the USP Drug Release Test 1
      for a CPM Extended-Release Capsule. The potency and content uniformity remained
      unchanged by the process. Dual coatings demonstrated a cumulative extension of
      release superior to the capability of a single coat. The new method is a viable
      alternative to hot-melt spray-coating methodologies. Organic solvents, spraying
      equipment, steam jackets, and/or heating tape are eliminated from the process. A
      reduction of equipment costs, setup time, and cleanup time may be realized. The
      method has demonstrated extended-release capabilities. No excessive attrition of
      potency or content uniformity has been noted. Additive, multiple coatings that
      have a cumulative effect on release retardation are feasible.

PMID- 9532605
TI  - Preliminary evaluation of an aqueous wax emulsion for controlled-release coating.
AB  - The purpose of this work was to evaluate the use of an aqueous carnauba wax
      emulsion (Primafresh HS, Johnson Wax) in a spray-coating process. This involved
      assessing the effectiveness of the wax in sustaining the release of the drug,
      theophylline. Second, the process by which the drug was released from the wax
      coated pellets was modeled. Finally, a method to determine the optimum blend of
      pellets with different wax thicknesses, in order to yield a zero-order release
      profile of the drug, was addressed. Nonpareil pellets were loaded with
      theophylline using a novel powder coating technique. These drug-loaded pellets
      were then coated with different levels of carnauba wax in a 6-in. diameter
      Plexiglas fluid bed with a 3.5-in. diameter Wurster partition. Drug release was
      measured using a spin-filter dissolution device. The study resulted in continuous
      carnauba wax coatings which showed sustained drug release profile characteristics
      typical of a barrier-type, diffusion-controlled system. The effect of varying wax
      thickness on the release profiles was investigated. It was observed that very
      high wax loadings would be required to achieve long sustained-release times. The
      diffusion model, developed to predict the release of the drug, showed good
      agreement with the experimental data. However, the data exhibited an initial lag
      time for drug release which could not be predicted a priori based on the wax
      coating thickness. A method of mixing pellets with different wax thicknesses was
      proposed as a way to approximate zero-order release.

PMID- 9532606
TI  - Influence of swelling degree on release of nicardipine hydrochloride from acrylic
      microspheres prepared by solvent evaporation method.
AB  - The purpose of this study was to prepare and evaluate an enteric coated dosage
      form of nicardipine hydrochloride (NCH)-loaded microspheres for delivery over a
      12-hr period. Microspheres containing Eudragit RS and L with different ratios
      were prepared by solvent evaporation method and the effect of swelling on the
      release rate and characteristics was investigated. The change in the diameters of
      microspheres with time in simulated intestinal fluid (pH 7.5) at 37 degrees C has
      been studied. Drug release was determined using the flow-through cell method, and
      related to the degree of swelling (Q) of the microspheres. Q values in turn
      depended on the ratio of Eudragit RS-L used. Release of NCH from microspheres
      increased with Eudragit L amount, but no controlled-release pattern was observed.
      Q values > or = 18.88 caused a slow initial release followed by an accelerated
      release. Microspheres with an Eudragit RS-L ratio of 1:5.7, Q value of 38.71, and
      drug release rate of 0.155% min-1 exhibited a remarkable delayed time for erosion
      to begin (120 min). Thus, microspheres prepared from this formulation may provide
      an effective enteric dosage form, releasing NCH at a predetermined rate.

PMID- 9532607
TI  - Morphology and surface properties of blends of Eudragit RS with different
      poly(ethylene glycol)s.
AB  - The purpose of this study was to investigate the morphology and surface
      properties of blends of Eudragit RS, a hydrophobic polymer mainly used for film
      coating, and poly(ethylene glycol)s (PEG), amphiphilic polymers used as softeners
      for films. Blends of Eudragit RS and PEGs were prepared as films using the
      casting technique from methylene chloride. The morphology of those films was
      evaluated by scanning electron microscopy before and after treatment with water.
      Sessile drop technique was used to measure solid/liquid contact angles in order
      to calculate surface free-energy parameters and to investigate phase separation
      using the Cassie-Baxter approach. Films containing 20, 40, 50, and 60% PEG 3400
      and PEG 6000 appeared morphologically unchanged after treatment with water; no
      phase separation was noticed. Films containing PEG 14,000 after treatment with
      water showed the presence of a solid emulsion in the range 40, 50, and 60% PEG; a
      multiple solid emulsion was shown for films containing 60% PEG 20,000. The
      presence of two-phase systems was shown using contact angle measurements and
      results were in agreement with microscopic analysis. Calculated surface free
      energy parameters indicated that PEG 3400 and 20,000 in a critical concentration
      of 10% can modify surface parameters of Eudragit RS: for PEG 6000 and 14,000 this
      critical concentration was found to be between 10 and 20%. The surface polarity
      of PEG 3400, 6000, and 14,000 was found to be drastically reduced upon addition
      of 5% Eudragit RS; spontaneous surface layering of Eudragit RS could be
      reasonably hypothesized for PEG 3400. This study revealed that surface parameters
      of a polymer can be modified in the presence of a relatively small amount of a
      second material.

PMID- 9532609
TI  - The imaging of a controlled-release pellet formulation using scanning electron
      microscopy--potential for artefact generation.

PMID- 9532608
TI  - Improvement of nalbuphine bioavailability through rectal administration of a
      prodrug.

PMID- 9532610
TI  - Cardiovascular pharmacology of SKP-450, a new potassium channel activator, and
      its major metabolites SKP-818 and SKP-310.
AB  - The cardiovascular effects of SKP-450, a newly synthesized potassium channel
      activator, and its two major metabolites SKP-818 and SKP-310 were evaluated on
      isolated rat aorta and in freely moving rats and anesthetized beagle dogs. The
      rank order of potency in relaxing rat aorta precontracted with norepinephrine was
      SKP-450 > SKP-818 > Lemakalim > SKP-310 (EC50: 0.12, 0.55, 0.71 and 5.89 mumol/l,
      respectively). In rats, SKP-450, SKP-818 and lemakalim (3-100 micrograms/kg,
      i.v.) induced a dose-dependent decrease in mean arterial pressure (MAP; ED20:
      9.8, 11.7 and 22.4 micrograms/kg, respectively) followed by reflex tachycardia.
      In dogs, SKP-818 and SKP-310 (0.3-1,000 micrograms/kg, i.v.) had quite similar
      hemodynamic profiles to SKP-450 but with a smaller potency. SKP-450, SKP-818 and
      SKP-310 dose-relatedly decreased MAP (ED20: 2.6, 4.2 and 588.8 micrograms/kg,
      respectively). They slightly increased left ventricular positive dP/dtmax with a
      transient decrease at the highest dose, while inducing a dose-related decrease in
      rate-pressure product, tension time index and systolic time. SKP-450, SKP-818 and
      SKP-310 induced a marked dose-dependent increase in coronary blood flow (Emax:
      172.8, 257.9 and 178.7%, respectively) with less effects on blood flow through
      other arteries. Glybenclamide antagonized all the hemodynamic effects of SKP-450
      in rats and dogs, whereas propranolol antagonized its reflex tachycardia in rats.
      These results indicate that SKP-450 is a potent coronary and peripheral
      vasodilator in rats and dogs activating ATP-sensitive potassium channels and that
      SKP-818 and SKP-310 exert a similar hemodynamic profile to the parent compound
      with equi- and weaker potency, respectively.

PMID- 9532612
TI  - Protective effect of nifedipine against carrageenan-induced inflammation.
AB  - Administration of carrageenan (CA; 0.5 mg) to the plantar tissue of rats resulted
      in reversible inflammatory injury. The edema was monitored by changes in paw
      volume using a plethysmometer. Simultaneous administration of CA and nifedipine,
      intraperitoneally, at different doses (10, 20 and 50 mg/kg) prevented the
      inflammatory action, and the effect was dose- and time-dependent. In order to
      improve the nifedipine effects, we prepared liposomed nifedipine which,
      administered intraperitoneally, showed a greater anti-inflammatory action. In the
      presence of the L-type channel agonist Bay K 8644, the inflammation produced by
      CA increased and it was counteracted by free or liposomed nifedipine. The
      significance of these findings with respect to the mechanism of the anti
      inflammatory action of nifedipine is discussed.

PMID- 9532611
TI  - TRK-530 inhibits accumulation of superoxide anions derived from human
      polymorphonuclear leukocytes and bone resorption induced by activated
      osteoclasts.
AB  - TRK-530, a newly synthesized bisphosphonate, was assessed for its effects on the
      accumulation of superoxide anions derived from human formyl-methionyl-leucyl
      phenylalanine-stimulated polymorphonuclear leukocytes (PMN), and for its effects
      on bone resorption using a pit formation assay. TRK-530 concentration-dependently
      inhibited superoxide accumulation derived from PMN and osteoclast pit formation
      stimulated by 1,25-dihydroxyvitamin D3. Incadronate and risedronate had a strong
      inhibitory effect on pit formation, but no antioxidative activity. These data
      suggest that the anti-bone resorption activities of TRK-530 are possibly
      unrelated to its antioxidant properties. However, it is difficult to conclude at
      present which mechanisms play the most important role in the anti-bone resorption
      activities of TRK-530.

PMID- 9532614
TI  - Physiological effects of macrocycle 1 on the rabbit corpus cavernosum.
AB  - When the penis is in the flaccid state, the corpus cavernosum smooth muscle is
      under adrenergic control in order to maintain the sinusoids in a contracted
      condition (primarily via alpha-adrenergic stimulation). Penile erection is
      mediated by relaxation of corporal smooth muscle through a variety of direct and
      indirect mechanisms. Pharmacological agents that either inhibit alpha-adrenergic
      transmission or facilitate corporal smooth muscle relaxation will be beneficial
      for penile erection. Preliminary studies on macrocycle 1, a novel bioactive
      agent, demonstrated that this compound inhibits receptor-stimulated contraction
      without significantly altering field-stimulated contraction. The current study
      was designed to determine the physiological effects of macrocycle 1 on the
      response of the rabbit corpus cavernosum to various forms of stimulation.
      Sexually mature male New Zealand White rabbits were used in this study. The
      corpus cavernosum was dissected sharply from the removed penis and two
      longitudinal strips were prepared for isometric tension studies. Each strip was
      prestimulated with 200 mumol/l phenylephrine to produce a maximal contraction.
      The influences of macrocycle 1 (15.6, 62.5, 250, 1,000 mumol/l) on both the
      contractile response to phenylephrine and the relaxant effects of field
      stimulation, carbachol, ATP and nitroprusside were determined. The results
      demonstrated that although basal tension was not altered, the contractile
      response to phenylephrine was decreased by 5, 18, 47 and 57%, respectively, by
      the different concentrations of macrocycle 1. The degree of relaxation induced by
      field stimulation of various frequencies was significantly enhanced by macrocycle
      1 in a concentration-dependent manner. Similarly, the degrees of relaxation
      induced by bethanechol, ATP and nitroprusside were all significantly enhanced in
      a concentration-dependent manner. The conclusion from this study is that
      macrocycle 1 significantly inhibits phenylephrine-stimulated contraction and
      significantly enhances field-stimulated and pharmacologically induced relaxation.
      Although the mechanisms of action are not clear, its physiological effects on the
      rabbit corpus cavernosum implicate a potential for the treatment of erectile
      dysfunction.

PMID- 9532613
TI  - Comparative analgesic activity of nimesulide and diclofenac by intramuscular
      route: correlation with pharmacokinetic profile of nimesulide.
AB  - Nimesulide, a selective cyclooxygenase-2-inhibiting nonsteroidal anti
      inflammatory drug, has been found to be a potent anti-inflammatory and analgesic
      drug, when administered orally, rectally or topically. The aim of the present
      study was to evaluate the comparative efficacy of intramuscularly injected
      nimesulide with that of diclofenac and to elucidate the pharmacokinetic profile
      of this formulation. Swiss albino mice were used in the experiment. Analgesic
      activity was tested using the acetic acid writhing test and the tail-flick
      latency test. Plasma levels of nimesulide and its active metabolite,
      hydroxynimesulide, were determined by a HPLC method. A peak analgesic effect was
      observed between 60 and 120 min, while Cmax (10.6 +/- 3.8 micrograms/ml) of
      nimesulide was reached at 60 min (Tmax). Analgesia was induced within 15 min of
      administration of nimesulide and was significantly higher than that of diclofenac
      at 90 and 120 min posttreatment in the writhing reflex and at 60 and 90 min in
      the tail-flick latency test. The results indicate that intramuscularly injected
      nimesulide may be an alternative mode of administration in uncooperative patients
      or when immediate analgesic effects are warranted.

PMID- 9532615
TI  - Antiprogestin-mediated inactivation of cytochrome P450 3A4.
AB  - Based on previous observations of very short periods of linearity for
      antiprogestin metabolite formation and the presence of a common tertiary amine
      moiety in each compound as the principal site of their metabolism, we
      hypothesized that mifepristone, lilopristone and onapristone are oxidized by
      cytochrome P450 (CYP) 3A4 to reactive nitroso species that complex the heme of
      the enzyme, thereby inactivating it. Upon preincubation with human liver
      microsomes in the presence (but not the absence) of NADPH, mifepristone inhibited
      midazolam 1'-hydroxylation, a marker of CYP3A4 catalytic activity, very potently
      (IC50 approximately 3.5 mumol/l) and extensively (by approximately 87%).
      Lilopristone and onapristone also displayed NADPH and time-dependent inactivation
      of CYP3A4 with characteristics very similar to mifepristone. These data support
      antiprogestin-mediated inactivation of CYP3A4 and suggest the potential for drug
      drug interactions and time-dependent nonlinearities in pharmacokinetics upon
      their long-term administration.

PMID- 9532616
TI  - Sn-mesoporphyrin suppression of hyperbilirubinemia in EHBR/Eis rats, an animal
      model of Dubin-Johnson syndrome.
AB  - Sn-mesoporphyrin (SnMP), a potent inhibitor of heme oxygenase (HO), controlled
      hyperbilirubinemia in rats of the mutant strain EHBR/Eis. This mutant strain
      displays pronounced conjugated hyperbilirubinuria and dark pigmentation of
      hepatocytes, characteristics of the Dubin-Johnson syndrome. SnMP administered at
      a dose of 10 mumol/kg body weight produced an immediate decrease in plasma
      bilirubin concentrations which could be maintained by weekly injections of this
      synthetic heme analogue. Marked inhibition of HO activity was demonstrated in
      liver, kidney and spleen but not in brain. These results demonstrate that SnMP
      can lower plasma bilirubin concentrations for extended periods in a new mutant
      rat model of Dubin-Johnson syndrome.

PMID- 9532618
TI  - Test equating: what, why, how?
AB  - The purpose of this paper is to introduce test equating, including its concept,
      needs, and methods, to the field of physical education and exercise science. Both
      traditional and item response theory (IRT) equating methods, along with data
      collection designs, were described in detail, and the advantages and
      disadvantages of these methods were also introduced. In addition, equating errors
      and evaluation criteria, sample size, and related computer programs were
      introduced. Using an existing data set of sit-up tests, a test-equating
      application was illustrated through a step-by-step example. As a result, two sit
      up tests were equated onto a common scale, and equating accuracy was evaluated
      using both equating and cross-validation samples. Finally, benefits and potential
      applications of test equating in assessing motor functions and skills, as well as
      future research challenges, were described.

PMID- 9532617
TI  - Changes in throwing by older adults: a longitudinal investigation.
AB  - This investigation examined change in a motor pattern requiring multisegmented
      coordination in older adults. The overarm throw was observed longitudinally in 8
      elderly individuals over 7 years. Data were evaluated using Roberton's (Roberton
      & Halverson, 1984) movement components. Contrasting the assumed pattern of aging,
      only small declines in movement form were observed. Individual cases revealed
      additional, noncategorizable declines within component categories, including
      slower movement speed and decreased range of motion. Increased trial-to-trial
      variability also was associated with change. These changes suggested that elderly
      participants coordinated their movements in a manner similar to younger
      participants but controlled them differently. The small changes observed in this
      investigation suggest that performance, at least for some skills, is more stable
      than traditionally assumed.

PMID- 9532619
TI  - The Sports Inventory for Pain: a confirmatory factor analysis.
AB  - This investigation was designed to assess the factorial validity of the Sports
      Inventory for Pain (SIP) which was completed by 182 undergraduate students.
      Responses were subjected to a confirmatory factor analysis designed to test the
      hypothesized underlying factor structure. Of five proposed subscales, only the
      items for the Cognitive and Coping subscales reasonably fit the hypothesized
      structure. To improve the fit of the model, factors were allowed to correlate,
      and the worst fitting item from each of the subscales was removed. The modified
      model also failed to adequately fit the data. Lastly, the items corresponding to
      the worst fitting subscale were dropped from the analysis. Again, the modified
      model failed to fit the data. Discussion suggests a possible respecification of
      the SIP.

PMID- 9532620
TI  - Practice effects on the timing and magnitude of antagonist activity during
      ballistic elbow flexion to a target.
AB  - This study examined changes in antagonist timing and magnitude in response to
      ballistic elbow flexion practice. Seventeen men performed 400 ballistic elbow
      flexion trials to a target in the horizontal plane over 4 days of testing. A
      potentiometer and microswitch system at the elbow axis of rotation of a
      manipulandum recorded angular displacement and movement onset. Surface electrodes
      (Beckman Ag/AgCl) monitored the triceps brachii lateral head, and the
      electromyographic (EMG) signals were bandpassed between 20 and 300 Hz. The
      antagonist EMG burst was divided in two: early low-level activity (ANT1), and the
      large portion of the burst which occurs near target achievement (ANT2). Movement
      time decreased from 178 ms on the first test day to 136 ms on the last session.
      As practice improved the speed of limb movement, onset of the first component
      (ANT1) remained unchanged, while the second component (ANT2) started earlier. The
      magnitude of both portions of the antagonist burst increased from the first to
      last test day, but the change in ANT2 relative to ANT1 was more pronounced. These
      findings are used to explain discrepant observations in the literature for the
      temporal measure.

PMID- 9532621
TI  - Temporal and spatial adaptations during the acquisition of a reversal movement.
AB  - Adjustments of the biphasic movement in a coincidence anticipation task were
      studied using an erroneous knowledge of results (KR) paradigm. Forty participants
      received either no KR, correct KR, erroneous (+100 ms) KR, or 100 trials of
      correct KR followed by 50 trials of erroneous KR. Kinematic analyses revealed
      that for this 100-50 KR group the extension part of the movement was temporally
      adjusted under the influence of erroneous KR. Although accompanied by a decrease
      in movement amplitude, this did not account for the temporal shift in movement
      outcome, because all groups showed a reduction in amplitude. It is argued that
      changing external time constraints mainly results in temporal adaptations.
      However, spatial adaptations do play a role in kinematic changes during
      acquisition.

PMID- 9532622
TI  - Contextual influences and goal perspectives among female youth sport
      participants.
AB  - This study investigated two research questions: (1) do goal involvement and state
      anxiety vary between athletic games and athletic practices? and (2) do goal
      orientations change over the course of a competitive season as a function of the
      perceived team motivational climate? Middle school athletes (n = 127) were
      assessed on goal orientations, goal involvement, state anxiety, and motivational
      climate. Results indicated that athletes were more task involved and less anxious
      in practice than in game situations, and task goal orientation changed over the
      season relative to perceptions of mastery and performance climates. These results
      may indicate that sport offers an environment different from the academic setting
      and that mainstream psychology theories need to be adapted for the sport context.

PMID- 9532623
TI  - Application of generalizability theory to measurement of activity in males who
      are not regularly active: a preliminary report.

PMID- 9532624
TI  - A note on the response complexity effect in eye movements.

PMID- 9532625
TI  - A test of retroactive inhibition as an explanation of contextual interference.

PMID- 9532626
TI  - Component variability during bimanual rhythmic movements: not all harmonic timing
      ratios are alike.

PMID- 9532627
TI  - Work efficiency during step aerobic exercise in female instructors and
      noninstructors.

PMID- 9532628
TI  - One-mile run performance and body mass index in Asian and Pacific Islander youth:
      passing rates for the FITNESSGRAM.

PMID- 9532629
TI  - An empirical evaluation of the prediction of maximal heart rate.

PMID- 9532631
TI  - A test for the screening of taste function.
AB  - The overall aim of the present study was to investigate a new method for the
      screening of taste function in a clinical context. Instead of dripping liquids
      onto the tongue, thin edible wavers were used. One-hundred healthy subjects
      participated in the study (41 male, 59 female; mean age: 52 years; age range: 20
      89 years). Supra-threshold taste stimuli were presented as flavoured wavers made
      from flour and water. Sequential testing was performed regionally on the anterior
      one-third of the tongue and as whole mouth testing. When comparing ratings for
      the 5 different wavers separately for regional and whole mouth testing,
      differences between qualities only emerged for regional testing. Women were found
      to have less difficulty in taste identification which was most pronounced for
      regional testing. No effects of the subjects' age were observed. In conclusion,
      the wavers were found to be easy to use; they have a shelf-life of 2 to 3 years
      and can be carried in the pocket. The results indicate that the wavers may be
      suited for the screening of gustatory function, especially in a clinical setting.

PMID- 9532630
TI  - Effects of proximity on the choice to be physically active or sedentary.

PMID- 9532632
TI  - Utility of the nasal model in gene transfer studies in cystic fibrosis.
AB  - Despite advances in the treatment for cystic fibrosis (CF), life expectancy for
      affected patients remains dramatically curtailed. Recent years have produced a
      spectacular increase in our understanding of the genetic, molecular and
      physiological bases of this disease. Gene transfer is a new and conceptually
      attractive potential treatment for CF. A number of centres have undertaken
      preliminary human gene-therapy trials. Central to these trials has been the use
      of the nasal model in gene transfer studies. While the eventual target of gene
      therapy in CF will be the lungs, the nasal administration of vector offers a
      number of advantages over the tracheobronchial tree in early experimentation.
      Implicit in the use of the nasal model is the potential for rhinologic variables
      to influence the results. We review our own gene transfer studies as well as
      series from other institutions, considering the role of nasal factors in the
      experiments' outcomes. Rhinologic variables may, at least partially, potentially
      explain the sometimes disparate results reported in this emerging area of
      scientific interest.

PMID- 9532633
TI  - Prevalence of sinusitis signs on MRI in a non-ENT paediatric population.
AB  - In a population of 100 children with suspected intracranial neurological disease,
      the overall prevalence of sinusitis signs on magnetic resonance images (MRI) is
      45%. This figure exceeds the adult prevalence of 39%, while the nature of the
      lesions is more severe in children. Furthermore, paediatric sinuses seem to be
      affected according to a different pattern: adults have mainly maxillary and
      anterior ethmoidal lesions, whereas in children the sphenoidal and posterior
      ethmoidal sinuses are frequently involved too. Among children, the overall
      prevalence increases in the presence of a history of nasal obstruction
      (prevalence: 50%) and recent upper respiratory tract infection (prevalence: 81%)
      as well as when bilateral mucosal swelling (prevalence: 80%) or purulent
      secretions (prevalence: 100%) are seen on anterior rhinoscopy.

PMID- 9532634
TI  - Rhinomanometry, sinus CT-scan and allergy testing in the diagnostic assessment of
      chronic nasal obstruction.
AB  - In order to assess how effective a combination of diagnostic methods, each
      addressing specific aetiopathogenic aspects, would be in uncovering the cause of
      common chronic nasal obstruction, we evaluated 45 consecutive adult subjects.
      They were submitted to rhinomanometry testing, sinus CT-scans and RASTs to
      prevalent allergens. Most, but not all, patients ended up showing abnormal
      results in at least one of the diagnostic procedures. Sinus pathology was, by
      far, the most frequent diagnosis, while allergy took second place, with a number
      of atopic subjects displaying sinusitis as well. On the other hand, septal
      deviations with a significant effect on nasal resistance were only seldom found
      to be the cause of chronic nasal obstruction.

PMID- 9532636
TI  - Assessment of cell surface glycoconjugates in normal, benign and malignant human
      nasal mucosa.
AB  - Aberrant glycosylation of proteins is a common characteristic of neoplastic
      changes. No reports exist relating cell surface glycoconjugates to normal, benign
      and malignant human nasal mucosa. Using lectin affinity histochemistry,
      glycoconjugate reactivities for peanut agglutinin (PNA), concanavalin A (Con A),
      Griffonia simplicifolia agglutinin II (GSA-II), soy bean agglutinin (SBA) and
      Ulex europaeus agglutinin l (UEA-I) were analysed in the following groups:
      normal, benign (polyp, papilloma, and inverted papilloma) and malignant (squamous
      cell carcinoma (SCC) alone, SCC arising in inverted papilloma, and
      adenocarcinoma). The positive rate of lectin staining was evaluated using a
      quantitative AutoCAD programme. We correlated glycoconjugate expression to
      clinical features, diagnosis, and malignant transformation. The positive rate of
      PNA after neuraminidase pre-treatment (NA-PNA) staining was higher in inverted
      papilloma, while all-negative in polyp and papilloma. NA-PNA staining may be used
      as a differential diagnostic tool. Both inverted papilloma portions and SCC
      portions of the SCC synchronized with inverted papilloma subjects showed similar
      Con A and NA-PNA staining patterns. The biological characteristics define
      inverted papilloma as a pre-malignant neoplasm. The positive rate of PNA staining
      was significantly higher in inverted papilloma (inverted papilloma transformed to
      SCC) compared to inverted papilloma alone. Hence, PNA staining may predict
      malignant transformation of inverted papilloma. However, further investigations
      are required to prove this possibly worthwhile prognostic marker.

PMID- 9532635
TI  - Alpha 1-receptors at pre-capillary resistance vessels of the human nasal mucosa.
AB  - The aim of the present study was to further characterise the alpha-adrenoceptors
      in pre-capillary arteries of the human nasal mucosa. Mucosa was obtained from
      patients undergoing endonasal surgery. From the isolated conchae small arteries
      (diameter: 90-220 microns) were dissected, avoiding any direct traumatisation.
      The arteries were mounted to a Mulvany-Halpern wire myograph allowing isometric
      registration of the vessel constriction. Receptor subtypes were characterised
      using the agonists noradrenaline, phenylephrine and oxymetazoline, and the
      antagonists prazosine and yohimbine. The EC50 values of the three agonists were
      in the micromolar range, whereas the Emax values differed. When maximal responses
      to the agonists were expressed as a percentage of a potassium-induced
      constriction, values for noradrenaline, phenylephrine and oxymetazoline amounted
      to 110%, 78% and 21%, respectively. The agonist effects were almost completely
      blocked by the alpha 1-receptor antagonist prazosine, whereas yohimbine, the
      alpha 2-receptor antagonist, did not affect the agonist responses. From these
      results it is concluded that the adrenoceptors in pre-capillary arteries of the
      mucosa in human central concha are of the alpha-type. Since the decongestive
      effect of alpha 2-receptor agonists is beyond any doubt, this subtype of the
      adrenoceptor must be present on the venous capacitance vessels.

PMID- 9532637
TI  - Increased eotaxin-mRNA expression in non-atopic and atopic nasal polyps:
      comparison to RANTES and MCP-3 expression.
AB  - Eosinophilic tissue infiltration of nasal mucosa typical for allergic rhinitis
      and chronic polypous sinusitis may be due to chemotactic activity of chemokines
      specific for eosinophils. The CC-chemokines eotaxin, RANTES and MCP-3 have been
      postulated to be involved in the recruitment of eosinophils to certain inflamed
      tissues. To explore their possible role in chronic polypous sinusitis we examined
      eotaxin-, RANTES- and MCP-3-gene expression in human nasal polyps and normal
      human nasal mucosa of patients undergoing endonasal surgery for treatment of
      chronic polypous sinusitis. Using gene-specific primers in semi-quantitative
      reverse-transcriptase polymerase-chain-reaction experiments we found elevated
      expression of eotaxin- and RANTES-mRNA but no MCP-3-mRNA in non-atopic and atopic
      nasal polyps when compared to normal nasal mucosa.

PMID- 9532638
TI  - Plasminogen activators in human nasal polyps and mucosa.
AB  - Fibrinolysis is one of the processes that are involved in inflammation. In this
      study we have investigated if it is also involved in bilateral nasal polyposis, a
      disease with an inflammatory component. Fibrinolytic activity in the nasal mucosa
      and nasal polyps has been studied in 10 patients with bilateral nasal polyposis.
      Tissue-type plasminogen activator (t-PA) and urokinase-like plasminogen activator
      (u-PA) activities and antigen levels have been determined in polyp tissue and
      control nasal mucosa. t-PA activity is higher in nasal mucosa (median: 4.26
      i.u./mg) as compared with nasal polyps (median: 0.65 i.u./mg; p = 0.03); u-PA
      activity is slightly lower in nasal mucosa (median: 0.040 i.u./mg) as compared to
      polyps (median: 0.065 i.u./mg; not significant). The percentage of u-PA to t-PA
      is 7.9% in nasal mucosa and 22.8% in nasal polyps (p < 0.01). The shift towards a
      higher u-PA/t-PA ratio in nasal polyps suggests an inflammatory process. Plasma
      levels of C-reactive protein are all within normal limits, which may suggest that
      PA activity is restricted to a local inflammatory reaction in the airway mucosa.
      The higher u-PA/t-PA ratio in nasal polyps and the higher levels of u-PA, when
      compared with the findings in other organs affected by inflammation, indicate
      that u-PA plays a part in the inflammatory events resulting in nasal polyps.

PMID- 9532639
TI  - On the "let-down" procedure in septorhinoplasty.
AB  - In septorhinoplasty, the classical modified and Cottle's technique may complement
      each other. The maxilla-premaxilla approach of Cottle can be an utmost tool.
      Combined "let-down" and "push-down" (LD/PD) procedures can be advantageous in
      case of: (1) lowering a prominent pyramid while preserving the original profile
      of the dorsum; (2) lowering a pyramid that, after removal with a rasp knife and
      scissors, remains too prominent; (3) equalizing a deviated bony vault; and (4)
      eliminating a cartilaginous hump while preserving the integrity of the upper
      lateral cartilage. Septum excisions should be done to provide space for LD/PD
      manoeuvres.

PMID- 9532641
TI  - [Experience gained at a specialized outpatient center].

PMID- 9532640
TI  - A rare case of nasal schwannoma with intracranial extension.
AB  - A rare case--only the fourth as known--of a nasal schwannoma with intracranial
      extension is presented. A 28-year-old Japanese man complained of right nasal
      obstruction and bleeding for one year. A biopsy indicated the presence of a nasal
      schwannoma. Computed tomography and magnetic resonance imaging demonstrated
      intracranial extension of the tumour. The patient underwent surgery with a
      combined intra- and extracranial approach. Reconstruction was performed using
      pericranial flaps. Surgical management of this tumour is also described.

PMID- 9532642
TI  - [Effect of multifactorial prevention of cardiovascular diseases on lifetime
      prognosis: ten-year follow-up].
AB  - AIM: Assessment of the probability of decreasing cardiovascular mortality by
      detecting and treating coronary patients and patients with arterial hypertension
      and correcting the risk factors. MATERIALS AND METHODS: A prospective ten-year
      registration of the mortality of the male population aged 40 to 59 years was
      carried out at a Moscow territory with two health centers. The subjects were
      routinely screened for coronary disease, arterial hypertension,
      hypercholesterolemia, excess body weight, tobacco smoking, insufficient exercise.
      During the first five years of the follow-up they were involved in treatment and
      prophylaxis measures varying in activity and direction (the two health centers
      were specialized in prevention and common treatment). CONCLUSION: Multifactorial
      prophylactic intervention helped delay untimely death in all the population
      examined, mainly due to detection of cardiovascular diseases. The life prognosis
      was improved most appreciably in the cases when the levels of risk factors were
      decreased due to multifactorial prevention in comparison with the life prognosis
      for subjects with a similar decrease of risk factors but without prophylactic
      intervention.

PMID- 9532643
TI  - [Problems in secondary prevention of arterial hypertension in primary health care
      system].
AB  - AIM: Assessment of the quality of follow-up of patients with arterial
      hypertension (AH) within the framework of primary health care system. MATERIALS
      AND METHODS: A retrospective analysis of outpatient case histories of 927
      patients with AH treated at 6 health centers in the city of Kemerovo in 1995-1996
      was carried out. A special table was created in order to assess the quality of
      follow up. This table included all data on the follow-up. RESULTS: The study
      revealed an insufficient volume of examinations of target organs over the latest
      two years: total analysis of the urine was carried out in only 572 patients,
      total cholesterol measured in 228, the fundus oculi examined in 384, and ECG
      performed in 615 patients; echoCG of the heart and major vessels was carried out
      in only 111 patients and loading tests in 24. Antihypertensive therapy was
      administered to 758 patients; only 216 of these took drugs regularly, 163 used
      none at all, and 543 patients took drugs only during exacerbations of disease.
      Very often they used ineffective drugs longer used now and caused numerous side
      effects: clofelin, adelphan, rauwolphine, dibasole, papaverine, magnesium
      sulfate. CONCLUSION: The quality of follow-up of patients with AH does not meet
      the modern requirements to follow-up due to various causes: 1) social neglect of
      patients; 2) physicians neglect modern recommendations on the diagnosis and
      treatment of AH; 3) physicians' efforts are not aimed at the prevention of
      disease complications, prolongation of the life span of patients, and improvement
      of the quality of their life; 4) patients are not ready to active treatment.

PMID- 9532644
TI  - [Efficacy of moxonidine, an imidazoline receptor agonist, in patients with
      essential hypertension].
AB  - AIM: Study of zint (moxonidine), a hypotensive drug with the central mechanism of
      action. MATERIALS AND METHODS: The hemodynamics and platelet functional activity
      were assessed in 30 patients with essential hypertension treated by zint in a
      daily dose of 0.4 mg, taken in the morning, for 3 months. RESULTS: By the end of
      treatment the systolic arterial pressure decreased by 23 +/- 4 mm Hg, diastolic
      by 15 +/- mm Hg, mean pressure by 17 +/- 2 mm Hg, and heart rate by 5 +/- 4
      str/min. Echography showed that myocardial hypertrophy decreased but negligibly.
      An evident decrease of ADP-induced platelet aggregation was observed. CONCLUSION:
      Zint therapy may be a most physiological method of arterial hypertension control.

PMID- 9532645
TI  - [Clinical and biochemical features of atherosclerosis main risk factors in
      children of probands with primary hyperlipidemia].
AB  - AIM: Study of the incidence of hyperlipidemias and coronary atherosclerosis risk
      factors. MATERIALS AND METHODS: A clinical and biochemical study of 35 children
      (25 men and 10 women aged 6 to 27 years) from 30 families of probands with
      primary hyperlipoproteinemias (HLP) was carried out. Use of modified risk factors
      (RF) in the examined group permitted the detection of hypodynamia in 25 subjects,
      obesity in 4, alcohol abuse and tobacco smoking in 1, and disorders of lipid
      metabolism in 31 (88%) cases. RESULTS: Hypercholesterolemia was detected in 26
      examinees, combined HLP in 1, hypoalphacholesterolemia in 3, and type V
      hyperlipoproteinemia in 1 case. The level of lipoprotein (a) was increased and
      positively correlated with xanthomatosis and the age of examinees. The level of
      basal immunoreactive insulin was within the normal range of values. Analysis of
      the relationship of this parameter and other coronary atherosclerosis RF revealed
      a correlation of the level of immunoreactive insulin and content of blood low
      density lipoprotein cholesterol. In only 2 of the 30 examined families of
      probands with primary HLP there were no disorders of lipid metabolism and other
      modified RF. CONCLUSION: Children, adolescents, and young people from families
      with primary HLP represent a risk group; they are to be regularly examined in
      order to prevent coronary disease and atherosclerosis and to detect and treat it
      in time.

PMID- 9532646
TI  - [Betacap efficiency in elderly patients with coronary heart disease and essential
      hypertension].
AB  - AIM: To assess the efficacy of long-acting propranolol in elderly patients with
      essential hypertension (EH) and coronary disease (CD). MATERIALS AND METHODS:
      Sixteen patients (mean age 60 years) with EH and CD were examined using ECG and
      echoCG, chest rheoplethysmography, Holter ECG monitoring, and exercise test.
      Betacap was administered once a day in doses 40 or 80 mg at 10.00 or 13.00.
      RESULTS: The drug exerted an antianginal and hypotensive effect. Energy
      expenditures of the myocardium decreased and exercise tolerance improved; the
      drug was more effective in patients with the hyperkinetic circulation and if
      taken at 10.00. CONCLUSION: Betacap is an effective antianginal and hypotensive
      agent, recommended for therapy of elderly patients with EH and CD.

PMID- 9532647
TI  - [Extracorporeal circulation methods in the treatment of nonspecific aortic
      arteritis].
AB  - AIM: Development of a protocol of multiple-modality treatment of patients with
      nonspecific aortoarteritis (NAA) making use of plasmapheresis and specific plasma
      adsorption of proteinases. MATERIALS AND METHODS: Six patients with NAA aged 15
      to 58 years were examined using ultrasonic dopplerography, magnetic imaging, and
      angiography of the large vessels. Red cell sedimentation rate was assessed,
      cathepsin G activity, antitryptic activity, and content of C-reactive protein in
      the blood measured. Drug therapy was supplemented by repeated sessions of
      plasmapheresis and specific plasma adsorption on immotin. RESULTS: After sessions
      of plasmapheresis (n = 17) and plasma adsorption (n = 13), increased cathepsin G
      activity dropped by at least 30% (in 3 patients it normalized), the content of C
      reactive protein decreased in the presence of normal antitryptic activity (in
      patients with decreased activity it normalized and in those with increased values
      a tendency to normalization was observed). Red cell sedimentation rate decreased,
      particularly so 1 and 2 months after treatment; the patients felt better.
      CONCLUSION: Multiple-modality treatment of NAA patients making use of
      plasmapheresis and plasma adsorption decreases the activity of the inflammatory
      process.

PMID- 9532648
TI  - [Antioxidant probucol: effects on free radical lipid peroxidation, blood rheology
      and course of angina pectoris].
AB  - AIM: Study of the effect of antioxidant probucol on free-radical lipid
      peroxidation, blood rheology, and course of angina pectoris in coronary patients.
      MATERIALS AND METHODS: The above parameters and clinical hemodynamic values were
      monitored over the course of probucol therapy in 48 men (mean age 54.8 +/- 1.3
      years) with coronary disease and angina of effort of the II-III functional class.
      RESULTS: Long therapy with probucol effectively inhibited free-radical lipid
      peroxidation, normalized lipid spectrum of the blood, and had a favorable impact
      on the course of angina pectoris. CONCLUSION: Probucol stabilizes the structure
      and function of red cells and platelets in coronary patients.

PMID- 9532649
TI  - [Ascolong: a new buccal dosage form of acetylsalicylic acid to be used and
      antiaggregant].
AB  - AIM: Study of the tolerance and pharmacodynamic and pharmacokinetic
      characteristics of ascolong, a new buccal dosage form of aspirin containing a
      very low dose of acetylsalicylic acid (ASA): 12.5 mg. MATERIALS AND METHODS: The
      study was carried out in 43 healthy men (assessment of the drug tolerance) and 19
      male patients with coronary disease or cerebrovascular disorders. In 10 patients
      the antiaggregant efficacy of ascolong administered once or regularly (for 2
      weeks) in a dose of 12.5 mg was compared with placebo, in 9 patients a random
      cross study of 2-week courses of ascolong and Russian aspirin tablets in a dose
      of 100 mg was carried out. Platelet aggregation was assessed on days 1 and 14 of
      each course before and 2, 4, and 24 h after the drug intake. RESULTS: Ascolong
      containing a very low dose of ASA exerts a reliable antiaggregant effect after a
      single and regular intake, although this effect is less manifest than after
      aspirin tablets. Profiles of ASA concentrations in the blood were studied.
      Transbuccal entry of ASA in systemic circulation decelerated its metabolism into
      a less active metabolite, salicylic acid, due to which fact the ASA microdose had
      an expressed antiaggregant effect. The drug was sufficiently well tolerated.
      CONCLUSION: The new buccal film form of aspirin containing a very low dose of ASA
      possesses a good antiaggregant effect and is promising in subjects with
      contraindications to oral intake of aspirin.

PMID- 9532650
TI  - [New cases of helicobacter pylori associated duodenal ulcer].
AB  - AIM: Generalization of the results obtained through analysis of examinations of
      new cases of duodenal ulcer (DU) with patients suffering from DU of different
      duration, made in two main aspects: the patients' Helicobacter pylori (HP) status
      determined by histological, bacteriological, immunological studies and rapid
      urease test and their clinical manifestations, including analysis of risk factors
      predisposing to peptic ulcer. MATERIALS AND METHODS: Two groups of patients with
      DU: 1) 23 new cases; 2) (a group of comparison) 43 patients with DU of different
      duration were examined. Family history, risk factors (smoking, alcohol
      consumption, use of nonsteroidal antiinflammatory agents), concurrent diseases
      were analyzed. Esophagogastroduodenoscopy (EGDS), ph metry, histological,
      bacteriological studies, rapid urease test and IgG antiHP determination were
      made. RESULTS: More than 95% of patients with DU were found to have HP just at
      the moment of diagnosis. New cases of DU have less HP colonization in the mucosa.
      The best diagnostic results were obtained with a combination of a histological
      study and a rapid urease test. 74% of new DU cases have scarring-ulcerative
      deformity of the duodenal bulk and, therefore, the onset of peptic ulcer was
      asymptomatic or mild. DU accompanied by hemorrhage averaged 4.5%. A third of new
      cases have simultaneously 2 ulcer defects in the duodenal bulb. The pains and
      symptoms of gastric dyspepsia are typical of the two groups of patients; however,
      of particular significance for their formation are functional disorders in new
      cases and organic changes in other patients. CONCLUSION: The comparison of the
      diagnostic techniques for HP allows the authors to recommend a combination of a
      histological study and a rapid urease test as the most informative tool.

PMID- 9532651
TI  - [Comparative study of epidemiology of spondylarthropathies in indigenous
      population of the Chukot peninsula and Alaska].
AB  - The paper sums up the many-year cooperative Russian-American studies of the
      epidemiology of spondylarthropathies in the arctic populations of the Chukot
      Peninsula and Alaska. AIM: Comparison of the epidemiology of spondylarthropathies
      in the indigenous population of the Chukot Peninsula and Alaska. MATERIALS AND
      METHODS: A universal design of investigation with the same diagnostic criteria
      was used in both countries. A total of 974 indigenous residents of the Chukot
      Peninsula were examined simultaneously, on the Alaska the sampling was formed as
      the residents applied for care. RESULTS: In both regions the study revealed 1) a
      high incidence of HLA-B27, reaching 40% in the Chukot Eskimos; 2) a similarly
      high incidence of spondylarthropathies varying from 2 to 3.4%; 3) a similar
      spectrum of diseases, including, primarily, ankylosing spondylarthritis and
      Reiter's syndrome and undifferentiated spondylarthropathies and (rarely)
      psoriatic arthritis. Among HLA-B27 positive adults, the incidence of
      spondylarthropathies in all groups is 4.2% and of ankylosing spondylarthritis
      1.5%. CONCLUSION: A high incidence of spondylarthropathies, varying from 2 to
      3.4%, was revealed in the Arctic populations of the Chukot Peninsula and Alaska
      with a high incidence of HLA-B27 antigen. Although the spectrum of detected
      diseases was similar in the two groups, ankylosing sponditis was more incident on
      the Chukot Peninsula, whereas on the Alaska reactive arthritis and
      nondifferentiated spondylarthropathies predominated, which can be explained by
      difference in the methods of examination.

PMID- 9532652
TI  - [Dynamic surface tension of blood and synovial fluid in rheumatoid arthritis].
AB  - AIM: Assessment of the dynamic surface tension (DST) of blood serum (BS),
      synovial fluid (SF) in various courses of rheumatoid arthritis (RA). MATERIALS
      AND METHODS: Forty three patients with RA and 63 apparently healthy individuals
      were examined. DST of BS and SF was determined in the computer-aided tensiometer
      and some blood biochemical parameters were also measured. RESULTS: DST of BS in
      patients with RA were found to be higher than the normal values and some
      parameters c beta 2 and beta 3) of BS DST did not significantly differ from the
      normal values whereas others (beta 1 and gamma proved to be much lower. Depending
      on the disease course variants, there were some differences in these DST changes.
      There was a feedback between DST parameters and the levels of immunoglobulins,
      beta 2-microglobulin, and lipids in blood. CONCLUSION: Assessment of BS and SF
      DST may be useful in the differential diagnosis of RA, in the determination of
      its intensity and prognosis, and therapeutical efficiency.

PMID- 9532653
TI  - [Hypothalamo-pituitary-thyroid system in patients with rheumatoid arthritis].
AB  - AIM: Study of the function of the hypothalamus-pituitary-thyroid system in
      rheumatoid arthritis (RA) MATERIALS AND METHODS: Three hundred and fifty patients
      with RA of different forms, stages, and intensity were examined. The blood and
      synovial fluid (SF) levels of thyroid-stimulating hormone (TSH), thyroxine (T4)
      and triiodothyronine (T3) were measured by immunoradiometric assay. RESULTS:
      Patients with RA were found to have higher T4 levels (in articular rheumatism,
      there was its negative correlation with the intensity of the process and in the
      presence of systemic manifestations of RA, there was a positive correlation).
      Blood T5 levels with higher RA intensity tended to increase in patients untreated
      with glucocorticosteroids. Blood TST concentrations showed an upward tendency
      which correlated with the intensity and stage of RA. Changes were also revealed
      in SF TST, T4, T3 levels. CONCLUSION: The changes in the secretion of TSH, T4, T3
      in patients with RA are caused by this pathological process and those in their SF
      levels affect the course of articular inflammation.

PMID- 9532654
TI  - [Physiotherapy in treatment of respiratory failure in patients with combined
      injuries at hospital stage of urgent medical care].

PMID- 9532655
TI  - [Immune system in residents of territories contaminated with radionuclides after
      Chernobyl accident].
AB  - AIM: Study of the immunity and nonspecific defense factors in subjects living at
      a territory contaminated with radionuclides at a density of 1-5 Ci/km2 after the
      Chernobyl accident. MATERIALS AND METHODS: A total of 144 subjects aged 18 to 82
      years living in the Sasovo region of the Ryazan district were examined. Three
      groups were distinguished with different density of contamination: 1) n = 54, 1-5
      Ci/km2; 2) n = 36, conditionally pure territory; and 3) n = 54, living at the
      interface of the two territories. Blood analysis was carried out, nonspecific
      defense factors studied in the NBT test, and cellular and humoral immunity
      parameters investigated. RESULTS: Values of the NBT test, levels of the natural
      inhibitory factor and IgA, counts and functional activities of T lymphocytes and
      their subpopulations differed but negligibly from those in subjects living at
      pure territories. On the other hand, the counts of large granular lymphocytes
      were decreased and the incidence of autoimmune reactions to thyroid hormone
      antigens increased in the population exposed to low-dose ionizing radiation,
      which might be due to incorporation of radioactive iodine. CONCLUSION: The
      detected changes in the population exposed to low-dose radiation indicate that
      the history of exposure cannot be neglected, for such an exposure causes
      development of some diseases or alters their course.

PMID- 9532656
TI  - [Unstable chromosome aberrations in lymphocytes of liquidators of the Chernobyl
      accident consequences].
AB  - AIM: Analysis of peripheral blood lymphocytes for detecting unstable chromosome
      aberrations in liquidators of the Chernobyl disaster consequences and in
      residents of territories contaminated after the accident. MATERIALS AND METHODS:
      Peripheral blood lymphocytes were tested for unstable chromosome aberrations in
      216 subjects who worked for different periods after the Chernobyl accident in
      1986-1987 in the 30-km zone and at adjacent territories. The results were
      correlated to the duration of stay in the zone, terms of examination after the
      work, exposure dose fixed in the files, deviations in the health status and blood
      values, and with similar data on 21 residents of the stringent control regions of
      the Gomel district and 265 patients with different hematological diseases and
      donor blood samples exposed in vitro. RESULTS: Chromosome aberrations detected in
      the examined group are represented by dicentrics, paired and nonpaired fragments,
      acentric rings, and gaps. CONCLUSION: Although not everything is yet clear, we
      consider that detection of unstable chromosome aberrations of the dicentric type
      in lymphocytes of subjects who participated in liquidation of the accident
      consequences in remote periods after exposure persuasively proves that a
      radiation exposure, no matter what its dose was, took place, and hence, there are
      good grounds for including the subjects with aberrations in the high risk group.
      On the other hand, the absence of such aberrations does not rule out the
      detrimental effect of radiation on the organism.

PMID- 9532657
TI  - [Twenty-five-year follow-up of a female patient with generalized familial
      amyloidosis].

PMID- 9532658
TI  - [Specialized training and impact of general clinical picture of internal diseases
      (to centennial of Moscow university medical faculty clinics opening)].

PMID- 9532659
TI  - [Department of outpatient therapy: and important component in training and
      continuous education of medical staff and improvement of population medical care.
      Summing up the ten-year activity of department].

PMID- 9532660
TI  - [Internology of family doctor].

PMID- 9532661
TI  - [Arrhythmogenic dysplasia of right ventricle].

PMID- 9532662
TI  - [Liquidators of the Chernobyl accident consequences: a decade since the
      accident].

PMID- 9532663
TI  - Factors in the emergence of food borne diseases.
AB  - Food borne diseases are an important public health problem. Over the past two
      decades, the epidemiology of food borne diseases has changed rapidly as a
      consequence of changes in the social environment and the ability of pathogens to
      adapt to new niches. Several newly recognized pathogens have emerged and well
      recognized pathogens have increased in prevalence or become associated with new
      food vehicles. Several factors have contributed to the changing patterns of food
      borne diseases, and addressing food borne diseases will require rapid
      surveillance and effective prevention strategies. This article examines these
      factors and briefly addresses prevention and control of food borne diseases.

PMID- 9532664
TI  - Microbial food borne pathogens. Salmonella.
AB  - All food animals are susceptible to infection with Salmonella, a genus of gram
      negative, nonspore-forming, usually motile, facultative anaerobic bacilli
      belonging to the family Enterobacteriaceae. Salmonella are differentiated into
      over 2200 serologically distinct types (serotypes) based on differences in
      somatic, flagellar, and capsular antigens. Infection with Salmonella may or may
      not lead to a sometimes fatal salmonellosis, a disease that can remain localized
      in the gastrointestinal tract as gastro-enteritis, or become generalized as a
      septicemia and affect several organ systems. Infected food animals that do not
      develop salmonellosis, and those that recover from the disease, become carriers
      of Salmonella and serve as sources of infection to humans and other animals.
      Apart from being a source of Salmonella food poisoning for humans, Salmonella
      contaminated food animal carcasses are also a concern because they are a source
      of antibiotic-resistant Salmonella.

PMID- 9532665
TI  - Microbial food borne pathogens. Campylobacter jejuni.
AB  - Campylobacter jejuni is the most common food borne bacterial pathogen and leading
      cause of food borne disease in humans in the United States and other
      industrialized nations. Approximately four million cases of human
      campylobacteriosis occur each year in the United States. Although the majority of
      cases consist of limited diarrheal illness, severe sequelae can affect a small
      portion of patients with campylobacteriosis that may include reactive arthritis
      and Guillain-Barre syndrome. Animal reservoirs primarily include poultry (C.
      jejuni) and swine (C. coli). Pathogen reduction during poultry processing and
      safe handling of raw poultry in the kitchen are needed to prevent illness.

PMID- 9532666
TI  - Microbial food borne pathogens. Escherichia coli O157:H7.
AB  - Escherichia coli O157:H7 has emerged in the past 20 years as a pathogen of public
      health importance. Although most E. coli are normal flora in the colons of humans
      and other warm-blooded animals, several strains are capable of causing disease in
      humans. In recent years, E. coli O157:H7 and other shiga-like toxin-producing
      strains have been transmitted via foods and caused disease ranging from bloody
      diarrhea, and in more severe cases, hemolytic uremic syndrome and
      thrombocytopenic purpura. The reservoir appears to be cattle and, perhaps, other
      ruminants. Control is difficult in nonheated foods due to the organism's
      tolerance to low pH. Only supportive, symptomatic treatment is available for
      affected humans, and means to eliminate carriage in livestock are not presently
      available.

PMID- 9532667
TI  - Transmissible spongiform encephalopathies in food animals. Human food safety and
      animal feed safety concerns for veterinarians.
AB  - This article presents a brief overview of transmissible spongiform
      encephalopathies (TSEs) using examples of diseases that provide evidence
      supporting oral transmission of the agent. Agent theories are described briefly
      in general terms. Scrapie, bovine spongiform encephalopathy (BSE), chronic
      wasting disease, and transmissible mink encephalopathy are discussed to improve
      disease recognition by the food animal practitioner. Control programs for scrapie
      and BSE are described and the role of the veterinarian in animal feed and human
      food safety is related to TSEs.

PMID- 9532669
TI  - Food borne disease summary by food commodity.
AB  - Microbial pathogens may be transmitted to humans via food animals and food animal
      products. A quick reference table is presented to provide easy access to food
      safety information related to the major food animal product areas. Included in
      the table are the pathogens, mode of transmission, public health impact, and
      control and prevention strategies for poultry, beef, dairy products, and pork.

PMID- 9532668
TI  - Other food borne infections.
AB  - This article presents an update of several emerging or reemerging pathogens:
      Yersinia, Cryptosporidia, Cyclospora, Brucella, and Mycobacterium. All of these
      zoonotic pathogens show evidence of food borne transmission. Yersiniosis is
      presented as an emerging pathogen that has as its major route of transmission
      preparation and consumption of pork products. New evidence is presented that
      supports the transmission of brucellosis via the food chain, especially through
      contaminated raw milk and cheese. While TB has limited transmission via raw milk,
      it is highlighted as a reemerging infection due to the development of multiple
      drug resistance. Public health veterinarians stand in an excellent position to
      recognize these emerging diseases and apply intervention strategies to prevent
      and control these infections in the future. This article is intended to raise
      their consciousness as to the management and medical practices that can diminish
      food borne transmission.

PMID- 9532670
TI  - Food borne microbial pathogens of cultured aquatic species.
AB  - This article provides a broad overview of microbial pathogens associated with
      marine and fresh water aquatic animals, including Vibrio species, Escherichia
      coli, Streptococcus iniae, Salmonella species, and Edwardsiella tarda.
      Historically, cultured fish were not considered important vectors of human
      pathogens. This situation is changing, partly due to increasing animal densities
      as a consequence of a rapidly growing industry and partly due to increasing
      awareness by health care providers of pathogens in aquatic species that may
      result in human illness. Concerns facing the industry are also discussed along
      with possible solutions.

PMID- 9532671
TI  - Listeriosis.
AB  - Listeria monocytogenes is ubiquitous in nature and is part of the normal flora of
      the distal portion of the intestinal tract of numerous animal species.
      Listeriosis is an emerging food borne disease that is responsible for
      approximately 1,700 cases of human illness each year and 650 deaths. Listeria is
      the cause of three main disease entities in animals and humans: neural, visceral,
      and reproductive. Clinical signs associated with the three forms are discussed
      along with diagnosis, therapy, prevention, and control.

PMID- 9532672
TI  - The National Animal Health Monitoring System. A source of on-farm information.
AB  - The National Animal Health Monitoring System is a program of the
      USDA:APHIS:Veterinary Services designed to collect, analyze, interpret, and
      disseminate data on the management and health of US livestock, poultry, and
      aquaculture populations. The system is comprised of a national program staff, the
      National Veterinary Services Laboratories, and a field component that includes
      state and federal animal health officials distributed throughout the United
      States. The system uses a variety of approaches (large national studies, on-going
      monitoring, and target short-term studies) to address high priority objectives
      for US animal agriculture defined through a far-reaching information-needs
      assessment process.

PMID- 9532673
TI  - National surveillance for antibiotic resistance in zoonotic enteric pathogens.
AB  - Treatment of food-producing animals with antimicrobial agents that are important
      in human therapy may present a public health risk by the transfer of resistant
      zoonotic pathogens from animals to humans. Resistant bacteria can diminish the
      effectiveness of antibiotics and demand the use of more expensive or less safe
      alternatives. In 1996, the Centers for Disease Control (CDC), United States
      Department of Agriculture (USDA), and Food and Drug Administration (FDA)
      established the National Antimicrobial Monitoring System to prospectively monitor
      changes in antimicrobial susceptibilities of zoonotic pathogens from human and
      animal clinical specimens, healthy farm animals, and carcasses of food-producing
      animals at slaughter plants. This article describes the development,
      implementation, and objectives of the monitoring system and presents initial data
      generated by the system.

PMID- 9532674
TI  - Pathogen Reduction and Hazard Analysis and Critical Control Point (HACCP) systems
      for meat and poultry. USDA.
AB  - The United States Department of Agriculture (USDA) Food Safety Inspection Service
      (FSIS) adopted Hazard Analysis and Critical Control Point Systems and established
      finished product standards for Salmonella in slaughter plants to improve food
      safety for meat and poultry. In order to make significant improvements in food
      safety, measures must be taken at all points in the farm-to-table chain including
      production, transportation, slaughter, processing, storage, retail, and food
      preparation. Since pathogens can be introduced or multiplied anywhere along the
      continuum, success depends on consideration and comparison of intervention
      measures throughout the continuum. Food animal and public health veterinarians
      can create the necessary preventative environment that mitigates risks for food
      borne pathogen contamination.

PMID- 9532675
TI  - Determining the burden of human illness from food borne diseases. CDC's emerging
      infectious disease program Food Borne Diseases Active Surveillance Network
      (FoodNet).
AB  - Food borne diseases cause a significant burden of illness in the United States.
      The Food Borne Diseases Active Surveillance Network (FoodNet), established in
      1995, continues to monitor the burden and causes of food borne diseases and
      provide much of the data to address this public health problem.

PMID- 9532676
TI  - [An experimental model of enteric klebsiellosis].
AB  - Acute enteric infection was reproduced in rabbits, used as an experimental model,
      receiving Aspergillus flavus metabolites with food for 15 days and inoculated
      rectally with enterotoxigenic strain Klebsiella pneumoniae K24 6723.
      Pathomorphological study revealed the penetration of Klebsiella into microplicate
      cells of the intestinal epithelium, the proliferation of bacteria in the lamina
      propria and in the cupolas of Peyer's patches, as well as in phagolysosomes of
      leukocytes and macrophages. The lesion of the mucous membrane in both large and
      small intestine, accompanied by the hyperplasia of lymphoid follicles, was noted.
      As a rule, surface epithelium was dystrophically changed and peeled off into the
      lumen of the intestine. The specificity of such lesion was confirmed by the
      detection of Klebsiella in Coons' direct immunofluorescence test. The
      experimental model confirmed the role of a decrease in immunological protective
      reactions of the body, caused the action of A.flavus metabolites, in the
      development of the infectious process, initiated by opportunistic enterobacteria.

PMID- 9532677
TI  - [The visualization of streptococcal cells by the use of fluorescein-bond
      dextran].
AB  - The method for the visualization of streptococcal cells, based on the phenomenon
      of binding between fluorescein isothiocyanate-labeled dextran and the surface
      structures of streptococci, is proposed. S.cricetus, S.sobrinus and S.faecalis
      strains were studied. The data obtained in this study were compared with the
      results of flow cytofluorimetry of these microbial cells. The stability of
      binding dextrans by microbes and the influence of ionic force on this process
      were determined at room temperature, +4 degrees C and -20 degrees C.

PMID- 9532678
TI  - [The phosphatase activity in representatives of the genus Francisella].
AB  - The comparative study of phosphatase activity in the representatives of the genus
      Francisella--F. tularensis, F. novicida, F. novicida-like, F. philomiragia-
      revealed that all the bacteria under study synthesized acidic phosphatase. The
      study also revealed that strains of the Central Asian subspecies possessed the
      highest enzymatic activity, while holarctic strains either produced no
      phosphatase at all, or produced less active phosphatase. Bacteria belonging to
      nonarctic F. tularensis subspecies and other representatives of this genus with
      the same area of circulation possessed the medium level of activity. Using
      isogenic F. tularensis variants as a model, we found out that the loss of
      virulence by bacteria was accompanied by an increase in phosphatase activity.
      Detergent (0.5% sodium dodecyl sulfate) was found to be capable of selectively
      inactivate this enzyme in the holarctic strains F. tularensis and F. novicida, F.
      novicida-like, F. philomiragia. The enzyme immunoassay of Francisella
      phosphatases made it possible to detect this enzyme in the nonarctic and Central
      Asian subspecies of F. tularensis and F. novicida, as well as in F. novicida
      like, characterized by different electrophoretic mobility. No phosphatase could
      be visualized in F. tularensis and F. philomiragia holarctic strains.

PMID- 9532679
TI  - [The development of bacterial growth stimulants from plants].
AB  - Dried bacterial growth stimulators in the form of water extracts of wild marjoram
      were developed; they produced a stimulating effect on Escherichia coli and
      Streptococcus pyogenes Dick 1 and had no influence on the growth of
      Corynebacterium xerosis 1911. The study aimed at finding out the active principle
      of the stimulator prepared from marjoram extract revealed that under experimental
      conditions marjoram extract could be divided into 3 fractions of these: fraction
      1 contained terpenic hydrocarbons, fraction 2 contained vitamins and vitamin-like
      substances, fraction 3 contained phenols, flavonoids, phenolcarbonic and fatty
      acids. Fraction 3 at a concentration of 0.0001% produced the best effect. The
      stimulating effect of extracts obtained from lime and aspen leaves, haw berries
      was demonstrated.

PMID- 9532680
TI  - [The role of persistence factors in the forming of a microbial biocenosis in the
      nasal mucosa in staphylococcal bacteria carriers].
AB  - The microbial biocenosis of the nasal mucosa under normal conditions and in cases
      of Staphylococcus aureus carriership was studied, taking into account the
      biological properties of symbionts in 159 persons. In S. aureus carriers the
      dysbiotic state of the intranasal microflora was established: the decrease of the
      index of total microbial contamination, the index of contamination with obligate
      coccal microflora and the index of specific diversity. The factors of the
      persistence and antagonism of dysbiotic microflora contribute to the mechanism of
      the development of dysbiosis. In the biocenosis of the carriers obligate
      microflora strains (Corynebacterium, Micrococcus and coagulase-negative
      staphylococci) with more pronounced interspecific antagonism or bacteriocinogeny
      were dominant.

PMID- 9532681
TI  - [The etiology of El Tor cholera].
AB  - Vibrio cholerae eltor has been shown to exist in two variants: epidemic (V.
      cholerae eltor Hly-, tox+) and nonepidemic, or endemic (V. cholerae eltor Hly+,
      tox-); each of these variants determines the corresponding form of manifestation
      of the infection among the population and requires a differentiated complex of
      antiepidemic measures, as well as different tactics for the treatment of
      patients.

PMID- 9532682
TI  - [The epidemiological situation in Russia in 1991-1996 with respect to morbidity
      from socially determined infectious diseases].

PMID- 9532683
TI  - [The epidemiological situation with respect to infectious diseases controlled by
      specific prophylactic remedies and the main trends in the prevention of this
      group of diseases in the Russian Federation].

PMID- 9532684
TI  - [The scientific, organizational and methodological bases for the epidemiological
      surveillance of streptococcal group A infection in a large city].
AB  - These investigations have made it possible to establish the extent and scale of
      the spread of streptococcal infection (group A) and its socioeconomic importance
      in Moscow, a great mega-police of the world. The deterioration of the
      epidemiological situation in recent years, accompanied by an increase in
      morbidity and mortality caused by streptococcal infection, has been demonstrated.
      The program and conceptual foundations of epidemiological surveillance on this
      infection in Moscow are presented. The aspects of epidemiological surveillance
      (informational and analytical, diagnostic, administrative) have been indicated
      and described. The order and direction of their realization have been determined.

PMID- 9532685
TI  - [Rubella in Russia: the detection of congenital rubella and the vaccination
      strategy and procedures].
AB  - The work on the evaluation of the role of rubella infection in the development of
      congenital malformations in newborn infants, as well as the immunogenic activity
      and tolerability of live attenuated vaccine Rudivax (Pasteur Merieux Connaught)
      was carried out in the process of selective immunization in the Perm region. The
      study made it possible to find out 15% of malformations in the structure of the
      congenital pathology of newborn infants, which appeared due to the infection of
      the fetus with rubella virus and were manifested by multiple development defects,
      congenital C.N.S. defects and valvular defects. The results of using vaccine
      Rudivax in the epidemiological trial demonstrated that the vaccine had high
      immunological activity and was well tolerated. The absence of postvaccinal
      complications after the injection of the live vaccine and the absence of the
      extinction of immunity in the presence antibodies were indicative of the
      possibility vaccination without preliminary serological examination.

PMID- 9532686
TI  - [Hep-A-in-Vac, a Russian cultured concentrated inactivated vaccine against
      hepatitis A].
AB  - The results of the study of the reactogenicity, safety and immunological activity
      of Russian cultural vaccine against hepatitis A are presented. The vaccine was
      found to have specific safety, moderate reactogenicity and pronounced
      immunological activity. In addition, the study of the prophylactic efficiency of
      the vaccine in the pre-epidemic period of the outbreak of hepatitis A morbidity
      in a group exceeding 14,000 adults was carried out. The study revealed high
      prophylactic efficiency of the vaccine (its efficiency rate was equal to 97.7%).
      On the basis of materials thus obtained vaccine "Hep-A-in-Vac" was recommended
      for use in medical practice for the prophylaxis of hepatitis A among adults.

PMID- 9532687
TI  - [The effect of immunomodulators on the development of antibodies to the
      diphtheria antigen in mice vaccinated with the DTP adsorbed vaccine].
AB  - An animal model for the study of the influence of immunomodulators on the
      development and preservation of postvaccinal antidiphtheria immunity was
      experimentally selected and the corresponding study was carried out. In this work
      the following immunomodulators were used: dibasol, prodigiosan, splenin,
      thymalin, reaferon, tactivin, methyluracyl. The study revealed that by day 120 of
      observation all immunomodulators stimulated the production of antibodies in
      higher titers than adsorbed DPT vaccine, introduced without immunomodulators. The
      most effective action was exhibited by splenin and prodigiosan (injected
      subcutaneously), dibasol and methyluracyl (administered orally). Two latter
      immunomodulators, if introduced prior to immunization, are the most promising
      preparations to be used in practical immunoprophylaxis.

PMID- 9532688
TI  - [A competitive analysis of the specificity of natural antibodies to the epitope
      of the bacterial cell wall peptidoglycan: the glucosaminylmuramyl dipeptide
      possessing adjuvant activity].
AB  - Natural antibodies to glucosaminyl dipeptide (GMDP), a component of bacterial
      cell-wall peptidoglycan, isolated from the serum of normal donors by thermal
      extraction, are capable of cross reaction with the determinant of the glycan
      chain: tetrasaccharide consisting of N-acetylglucosamine and N-acetylmuramic
      acid. The intensity of the interaction of natural anti-GMDP antibodies with a
      specific ligand is considerably higher than with tetrasaccharide. Natural
      antibodies to tetrasaccharide possess the properties of heterologous antibodies,
      i.e. the intensity of their interaction with a specific ligand (GMDP) is
      considerably higher than with a homologous ligand. Suggestion is made that GMDP
      is the specific antigenic determinant of peptidoglycan to which antibodies are
      formed in process of natural immunization. These antibodies react with different
      intensity with homologous (GMDP) and related (tetrasaccharide) haptens.

PMID- 9532689
TI  - [The cytokine-inducing activity of the Yersinia pestis "murine" toxin].
AB  - In this work the data obtained in the study of cytokinin-inducing activity of Y.
      pestis "mouse" toxin (MT) are presented. The study revealed that MT induced the
      synthesis of IL 1, IL 2 and TNF alpha. The most pronounced activity in MT was IL
      2 inducing activity having dose-dependent character: the effect increased with
      the decrease of the dose of the preparation. The maximum level of the synthesis
      of IL 2 was observed when very low doses of the preparation (0.01 microgram/ml)
      were used, which was characteristic of superantigens. The presented data suggest
      that IL 2 plays an essential role in the mechanism of immunopathological
      reactions stipulated by MT.

PMID- 9532691
TI  - [The spontaneous variability of populations of fungal strains in the genus
      Aspergillus--producers of allergen-active substances].
AB  - The method of genetic selection has been used for obtaining the fungal cultures
      of Aspergillus strains, producers of allergen-active substances. The natural
      variability of populations of A. fumigatus, A. niger, A. clavatus strains as
      regards the intensity of conidia germination has been studied. These fungal
      species are the etiological agents of mycotic lesions of the body in cases of
      immunodeficiency. As the result of this study, 3 Aspergillus species, stable as
      regards the intensity of conidia germination, have been selected. The selected
      Aspergillus producer strains are successfully used for obtained allergen-active
      substances. The isolated allergen are used for the specific diagnostics of mold
      mycosis and mycogenic allergy.

PMID- 9532690
TI  - [A comparative study of the information value of the immunofluorescence and
      immunochromatographic identification of Chlamydia trachomatis antigens in smear
      material from the cervical canal and of the cytological picture of a vaginal
      discharge in pregnant women].
AB  - The cytological picture of the vaginal discharge and scrape material, obtained
      from 30 pregnant women of the control group (not infected with C.trachomatis) and
      61 pregnant women with chlamydiosis; of these, in 42 women the comparative
      identification of chlamydiae by the methods of direct immunofluorescence and
      immunochromatography was carried out. Direct immunofluorescence was carried out
      with the use of a set of reagents "MicroTrak" (USA) and immunochromatographic
      identification was made with the use of a set of reagents "Clearview Chlamydia"
      (Britain). The comparison of the results of immunochromatography and direct
      immunofluorescence revealed that the sensitivity of the set "Clearview Chlamydia"
      was 100.0% in comparison with the data obtained in the examination of women with
      the use of the set "MicroTrak". The negative results coincided in 90.1% of cases.
      The common features of the cytological picture of vaginal samples taken from
      pregnant women were established. The optimum system of the examination of
      pregnant women suspected for chlamydiosis, as well as for the evaluation of the
      effectiveness of its treatment, was proposed.

PMID- 9532692
TI  - [The principles of the therapy of glanders in monkeys].
AB  - The effect of pathogenetic therapy in the normalization of homeostasis
      disturbances in monkeys has been shown under experimental conditions. Data on the
      possibility of using hemosorption in the treatment of severe forms of glanders
      are presented. The conclusion on the necessity of using complex treatment for the
      effective therapy of glanders in humans has been made.

PMID- 9532693
TI  - [The diagnosis of hepatitis C viral infection in blood donors and patients].
AB  - The data on the examination of 5139 serum samples, obtained from 3358 blood
      donors and 1781 somatic patients, for the presence of HCV, HBV and HDV markers.
      Antibodies (Ab) to HCV were detected, on the average, in 1.56% of the examined
      blood donors (207 persons). Of these, in 1994 HCV markers were detected in 1.98%
      and HBV markers in 6.74% of cases, while in 1995 these markers were detected in
      1.14% and 3.43% of cases respectively. The diagnosis of chronic viral hepatitis
      (mainly C) was verified in 14% of seropositive donors. In the group of somatic
      patients Ab to HCV were diagnosed in 130 examined patients (7.3%), in a half of
      the cases HCV and HBV coinfection being present. Similar percentage of
      coinfection was detected in blood donors. It should be pointed out that out of
      the total number of somatic patients only 4 patients had chronic viral hepatic
      diseases. Our data were compared with the data of medical statistics and were
      found to reflect the spread of HCV and HBV infection in the region among
      different groups of the population.

PMID- 9532694
TI  - [The Amben correction of disorders in the intestinal microbial colonization of
      newborn infants with perinatal pathology].
AB  - The examination of 49 newborn infants revealed that at the early neonatal period
      the character of the microbial colonization of the intestine depended on the kind
      of perinatal pathology: in lesions of the central nervous system and conjugation
      jaundice the deficiency of Bifidobacterium and Escherichia was detected; in
      hemolytic disease opportunistic bacteria were dominant simultaneously with the
      deficiency of lactoflora. The study of these infants, divided into two groups
      differing in the administration of Amben (an inhibitor of proteolytic enzymes),
      showed the efficiency of Amben which stimulated the growth and development of
      resident microflora in the intestine, thus contributing to the maintenance of
      eubiosis in a given group of infants with perinatal pathology.

PMID- 9532695
TI  - [The characteristics of the caseinolytic activity of the contents of the large
      intestine in dysbiotic states].
AB  - In the course of the study of the biochemical rapid method for the evaluation of
      microecological changes in the intestine by means of the test for the
      caseinolytic activity of fecal supernatants, the simultaneous presence of several
      enzymes in the samples under test was shown. Different degrees of the thermal
      inactivation of the active principle, linked with the expression of the positive
      caseinolytic sample, were established. The manifestations of caseinolytic
      activity, differing in their thermal stability, were found to have the
      proteolysis zone of equal size. The study showed the stability of this sign and
      its preservation during 1.5-2 years of storage of fecal supernatants in a
      refrigerator. Some details of making tests according to this method and the
      conditions ensuring the standard reproducibility of results were ascertained.

PMID- 9532701
TI  - [The outlook for the development of a vesicular meningococcal serogroup B
      vaccine].

PMID- 9532702
TI  - [Nonparenteral vaccines: the principles of their design and efficacy].

PMID- 9532703
TI  - [The principles in correcting secondary immunodeficiencies by using 2
      immunomodulators of differing character--purified staphylococcal anatoxin and
      likopid].

PMID- 9532704
TI  - [Muramyl dipeptide derivatives in experimental and clinical use].

PMID- 9532705
TI  - [An outbreak of acute intestinal infections among the personnel of a Moscow hotel
      (1)].

PMID- 9532707
TI  - [An outbreak of salmonellosis in the general education schools of Moscow: an
      epidemiological puzzle (1)].

PMID- 9532706
TI  - [A combined outbreak of intestinal yersiniosis and pseudotuberculosis in a
      children's health-promotion camp].

PMID- 9532708
TI  - [An outbreak of acute intestinal infections among the personnel of a Moscow hotel
      (2)].

PMID- 9532709
TI  - [Epilepsy in patients with ischemic brain disease].
AB  - The paper presents the results of follow-up study of 610 patients with ischemic
      stroke. In 52 patients (8.6%) there was observed symptomatic epilepsy conditioned
      by local causes (2 and more epileptic fits in anamnesis). The age of the onset of
      epileptic seizures was in the range 50-69 years, and men prevailed. From all 52
      patients with episyndrome 36 had only one stroke, 16 patients-two and more
      strokes. 14 patients had fits before the stroke development. Meanwhile in 10
      patients the fits were the first stroke symptoms (early) and in 28 individuals
      the fits arose 7 days after the stroke development (late). Significantly more
      severe disorders of dynamic praxis were revealed in psychologic examination of
      the patients with secondary generalized fits than of ones with partial seizures.
      Pathogenetic and clinical aspects of vascular epilepsy, interactions between
      transitory ischemic attacks and the fits which developed before the stroke are
      considered.

PMID- 9532710
TI  - [Tremor as a symptom of organic brain damage in individuals of young age].
AB  - Cases of young patients with different diseases of nervous system in which tremor
      was the main symptom, clinical peculiarities of trembling hyperkinesis in
      essential tremor, in olivopontocerebellar degeneration, in strionigral atrophia,
      in residual phenomena of organic brain damages as well as their differences from
      functional hyperkinesia are characterized. The data are presented on comparative
      efficiency of different methods of examination.

PMID- 9532711
TI  - [Syndrome of juvenile asthenic deficiency].
AB  - A clinical and follow-up study of 155 young adults with a symptomcomplex of
      "juvenile asthenic deficiency"--"endogener juveniler asthenischer
      Versagensyndrome" (J.Glatzel, G.Huber, 1968) was carried out. It was found that
      protracted states in the youth with prevalence of educational disadaptation,
      weakening of initiative, psychophysical fatiguability should be attributed to
      atypical depressions, characterized by predominance of ideatoric disturbances
      with obliterated thymic and motor components. Depending on the specificities of
      ideatoric disturbances, 3 basic typological varieties of such depressions were
      recognized, i.e. depressions with prevalence of inhibition, disautomatization or
      distortion of cognitive processes, which statistically correlated reliably with
      definite nosological forms (affective disorders, schizophrenia). Depending on the
      nosologic belonging the studied states differed also in frequency of comorbid
      disturbances (obsessive-phobic, depersonalization, overvalued ideas), which
      occurred significantly rarer in the cases of affective disorders, than in
      schizophrenia. On the whole, follow-up study revealed relatively favourable
      prognosis of youth endogenous depressions with a clinical picture of "juvenile
      asthenic deficiency": in cases of affective disorders the course of disease was
      more frequently in the form of a single cyclothymic attack, while in cases of
      schizophrenia it took the form of protracted atypical pubertal attack.

PMID- 9532712
TI  - [Neurophysiologic correlations of cognitive dysfunction in depressed patients
      with syndrome of juvenile asthenic deficiency].
AB  - Peculiarities of cognitive process were studied in 34 right-handed endogenously
      depressed patients with "juvenile asthenic deficiency" ("endogener juveniler
      Versagensyndrome" according to J. Glatzel and G Huber, 1968) by means of visual
      evoked potentials (EP) in the emotional recognition task. Two control groups
      consisted of 19 healthy individuals and 20 patients with other types of
      depressions. The main and control groups were matched for age, sex, handedness
      and education level. Compared to controls the patients with "juvenile asthenic
      deficiency" demonstrated highly significant alterations in indices of EP late
      negative wave in anterior areas of the left hemisphere which related to neither
      the nosology of "juvenile asthenic deficiency" (cyclothymia, schizophrenia) nor
      the types of dominant cognitive disorders. Dependence on both nosology and
      clinical subtype of asthenic deficiency was found only for separate
      characteristics of earlier EP waves. The results suggest the disturbance of the
      final stages of information processing and the decision making specific for
      "juvenile asthenic deficiency".

PMID- 9532713
TI  - [Excitability of spinal alpha-motoneurons in gunshot injuries of nervous trunks
      of lower limbs in patients in rehabilitation].
AB  - Excitability of functionally different alpha-motoneurons was studied in 62
      patients with gunshot injuries of nervous trunks of lower extremities both before
      and during process of rehabilitation by means of physical factors. The
      correlation of reactions of spinal cord motoneurons and the degree of injuries of
      nervous trunks was observed. Neuroapraxia of nervous trunks was accompanied by
      multidirectional alterations in reflex activity of large and small alpha
      motoneurons. It was depressed in axonothermesis and lost in simultaneous full
      anatomic interruption of ischiatic nerve and trunks of both fibular and tibial
      nerves. Under influence of physical factors the function of motoneurons was
      normalized in neuroapraxia and was improved in axonothermesis of nervous trunks.

PMID- 9532714
TI  - [Atarax in treatment of anxiety in outpatient clinic].
AB  - 50 patients (10 men, 40 women) with generalized anxiety (29), disorders of
      adaptation (15), somatoformed disorders (6), diagnosed according to ICD-10, were
      treated by atarax. Mean age of the patients was 42.4 years, average duration of
      the disease-1.9 years. Evaluation of efficiency was performed according to
      "Global Clinic Impression" scale, Hamilton rating scale for anxiety and
      depression (HAM-A and HAM-D) as well as according to FARD scale for anxiety. The
      patients were examined both before the treatment and on 14 and 28 days of
      treatment. According to "Global Clinical Impression" scale excellent and good
      results were observed in 66% of the patients. Unsatisfactory results were found
      in 10% of the cases. Reduction of the total HAM-A scores by 50% and more was
      observed in 48% of the patients. The same decrease was observed in 58% of the
      patients according to HAM-D scale and in 54% of the patients according to FARD
      scale. Following side-effects were noted: transitory sleepiness (36% of the
      cases), weakness (18%), headache (6%), changes of both appetite (6%) and body
      mass (6%), slight mucosa dryness (2%). In one case skin allergic reaction in form
      of urticaria bullosa took place and the therapy was interrupted.

PMID- 9532715
TI  - [Neuropsychologic method in diagnosis of mild dementia in elderly and senile
      patients].
AB  - Clinical neuropsychologic investigation was performed in 95 patients of elderly
      and senile age with mild dementia: 20 individuals with Alzheimer's disease (AD),
      25 patients with senile dementia of Alzheimer's type (SDAT), 25 patients with
      vascular dementia (VD) and 25 patients with combined dementia of vascular and
      Alzheimer's types (DAT/VD). Clinical diagnosis of mild dementia was performed
      according to ICD-10. Neuropsychologic study was based on the theory and method of
      A.R. Luria. Syndrome of disorder of high psychic functions (HPF) in patients with
      mild SDAT was characterised by pathology of frontal cerebral structures and by
      significantly less defects of profound cerebral structures. According to the
      examination results the group of patients with mild AD was divided into 2
      subgroups: 1) patients in which syndrome of HPF disorders was determined by
      pathology of parietal-temporal and profound cerebral structures and 2) patients
      with dysfunction of profound and frontal cerebral structures. Symptoms associated
      with profound cerebral structures were the main ones in patients with mild VD.
      Syndrome of HPF disorder included in mild DAT/VD symptoms connected with
      subcortical and profound brain structures as well as with frontal structures too.
      Besides, there were also defects in posterior frontal and parietal structures of
      the brain.

PMID- 9532716
TI  - [Network planning of psychiatric services and professional education in
      contemporary psychiatry].
AB  - Necessity of perfection of both facilities and professional activity of
      psychiatric service in Russia was grounded. The analysis of legislation and
      standardized documents of the last 5 years illustrates the process of elaboration
      and realization of both federal and regional programs of financial and technical
      support of psychiatric institutions in the country. This process was considered
      with regard of the region's type, necessity of continuous (both pre- and
      postdiploma) education of psychiatrists, psychotherapeutists, medical
      psychologists and specialists on social care. Mechanisms of financial support of
      the measures directed at differentiation of psychiatric care were proposed.

PMID- 9532717
TI  - [Juvenile population in psychoneurologic outpatient clinic].
AB  - Adolescents with mental pathology borned in 1977 were followed up in
      psychoneurological outpatient clinic for a period of 3 years (1994-1997). The
      problems of primary care and delay of contact of adolescents with psychiatrists
      were investigated. The most characteristic diagnostic difficulties, cases of
      change of diagnosis, development of social-occupational adaptation and
      suitability for military service are analyzed.

PMID- 9532718
TI  - [Place of heboid syndrome in psychopathological registries of juvenile age (on
      delusional features of heboid syndrome)].

PMID- 9532719
TI  - [Biological motivations in systemic organization of brain function].

PMID- 9532720
TI  - [Xenotransplantation in treatment of central nervous system diseases].

PMID- 9532721
TI  - [Hyperkinesias of fascial muscles-possible approach to classification and wording
      of diagnosis].

PMID- 9532722
TI  - [Vertebroneurology and manual therapy].

PMID- 9532723
TI  - The effects of spatial visualization and students' sex on mathematical
      achievement.
AB  - Sex differences in mathematical achievement and spatial visualization skill were
      examined in a sample of 724 Norwegian sixth-grade students. Boys had
      significantly higher mean mathematics scores than girls. Significant sex
      differences favouring boys were found in the subsamples of most difficult tasks,
      but not in the subsamples of easiest tasks. No significant sex difference in
      spatial visualization was found. The hypothesis that boys' superior achievement
      in mathematics is due to a superior ability in spatial visualization was not
      supported. Although the effect of spatial visualization on mathematical
      achievement increased significantly up to a certain level of mathematics task
      difficulty, the hypothesis that the effect of spatial visualization on
      mathematical achievement increases with increasing task difficulty was not fully
      supported. With increasing mathematics task difficulty, it is hypothesized that
      boys, more than girls, will benefit from spatial visualization. This hypothesis
      was not supported by the present elementary school data.

PMID- 9532724
TI  - On random generation and the central executive of working memory.
AB  - Four experiments explore participants' attempts to generate random sequences.
      Experiment 1 showed that oral random number generation is strongly affected by
      both response speed and response set size, in contrast to a random key-pressing
      task in Expt 2. Expt 3 confirmed differences between output modalities in the set
      size effect, and Expt 4 indicated that an important source of difficulty in
      producing random numbers orally lies in the requirement to represent candidate
      choices. Across experiments, data show a strong tendency on the part of
      participants to suppress response repetitions, an effect which decays over
      intervening responses. Whilst consistent with the possibility that random
      generation taps some executive functions, findings suggest the need to expand
      current models of attentional control in working memory to account for distinct
      constraints.

PMID- 9532725
TI  - Flashbulb memory assumptions: using national surveys to explore cognitive
      phenomena.
AB  - Implicit in most flashbulb memory research are three assumptions: that major news
      events will be important for almost everyone in the chosen sample, that people's
      ratings of memory quality are reliable and that a detailed recollection of
      personal circumstances implies a vivid memory. Using two general population
      surveys of Great Britain (total N = 3160), we examine each of these assumptions
      for two events that have recently been used in flashbulb memory studies: Margaret
      Thatcher's resignation as Prime Minister and the Hillsborough football disaster.
      The results emphasize the importance of careful sampling of both participants and
      events, and question whether flashbulb memories are as vivid as originally
      hypothesized. This type of research is rare within the flashbulb memory
      literature on account of the large sample sizes and the use of samples
      representative of the general population. This allows us to return to Brown &
      Kulik's (1977) original emphasis on group differences and re-evaluate their
      findings.

PMID- 9532726
TI  - Dioxin contents in fly ashes of MSW incineration in Taiwan.
AB  - Fly ashes from three municipal solid waste (MSW) incinerators in Taiwan were
      collected and segregated into different fractions for determining the physical
      and chemical properties and dioxin contents. Analysis of ashes with each fraction
      indicated that fine particles had higher dioxin contents than large particles.
      Dioxin homologue components of ashes generated from large-scale mass burn MSW
      incinerator were less toxic than that from small-scale batch incinerators, and
      contained less non-2,3,7,8 PCDD/Fs. Correlation analysis did not reveal a
      consistent trend between dioxins content and ashes' physical properties, while
      strong positive correlation was found between dioxins content and chloride
      content. Positive correlation between dioxin content and heavy metals content
      such as copper and zinc in the fly ash was also established.

PMID- 9532727
TI  - Decline in PCB levels in otters (Lutra lutra).
AB  - A decline in total PCB levels in tissues of otters (Lutra lutra) from England and
      Wales, averaging 8% per year over the period 1983-1992, is reported. Mean PCB
      levels are now unlikely to pose a threat to otter populations.

PMID- 9532728
TI  - Industrial pollutants in ground waters from northern Milan.
AB  - Ground water samples from an industrialised area near Milan were analysed by gas
      chromatography-mass spectrometry (GC-MS) to identify the main pollutants and to
      quantify two classes of chemicals: polychloro-1,3-butadienes (PCBD) and some
      aromatic amines. The water contained several halogenated aromatic and aliphatic
      compounds and heavy contamination due to PCBD, probably arising from contaminated
      land where a disused chemical plant is located. All the samples contained low
      levels of aromatic amines indicating a diffuse contamination probably arising
      from different sources.

PMID- 9532729
TI  - Fate and risk evaluation of persistent organic contaminants and related compounds
      in Victoria Harbour, Hong Kong.
AB  - The Environment Protection Department of Hong Kong has a monitoring program for
      persistent organic contaminants in sediments of Victoria Harbour, the main
      harbour of Hong Kong. A fugacity model has been used, based on this sedimentary
      data, to estimate inputs to the system (probably from sewage, stormwater and
      industrial discharges) as well as the fate of the contaminants, particularly in
      terms of the aqueous and biotic concentrations. The risk of deleterious effects
      on the natural marine system, as well as on the consumers of seafood from the
      system, was carried out using the estimated aqueous and biotic concentrations
      together with accepted environmental quality guidelines. The result of our
      analysis indicated that the chlorohydrocarbons, PCBs (as Aroclor 1254) total DDT
      and total HCH pose a significant risk, and probably have caused damage to the
      marine ecosystem as well as posing a hazard to seafood consumers. Much higher
      concentrations of the less toxic total alkanes, nonaromatic hydrocarbons, linear
      alkyl benzenes and the compounds giving a unresolved complex mixture (UCM) cannot
      be evaluated due to a lack of environmental guidelines and the complexity of
      these substances. However, it is probable that these substances add adverse
      effects to those due to the other contaminants.

PMID- 9532730
TI  - Effect of the gasoline additives on PAH emission.
AB  - PAH emission from the powered engines fueled by a 95 leadfree gasoline (95-LFG),
      a 92 leadfree gasoline (92-LFG) and a Premium leaded gasoline (PLG) with two
      gasoline additives (SA and SB) were collected using a PAH sampling system with a
      particulate interception device. Twenty one PAHs were analyzed primarily by an
      GC/MS, while eight metal elements were determined mainly by an ICP-AES. This
      investigation showed that the gasoline additives contain more amounts of
      carcinogenic PAHs than gasolines do. Blending these additives do raise the PAH
      content in the gasolines, simultaneously, will emit more amount of PAHs from the
      tailpipe of engine exhaust. It is suggested that before a gasoline additive is
      commercialized, an assessment on its PAH emission should be evaluated to make
      sure that the additive will not emit more PAHs and cause adverse effect on public
      health.

PMID- 9532731
TI  - The combination of photocatalysis and ozonolysis as a new approach for cleaning
      2,4-dichlorophenoxyaceticacid polluted water.
AB  - Treatment of 2,4-D polluted waters with photocatalysis leads to the buildup of
      high concentrations of the long living intermediate 2,4-DCP. A new approach using
      a combination of ozonolysis and photocatalysis gave better degradation results
      with lower intermediate concentrations. The advantages of photocatalysis giving a
      constant decline in TOC and of ozonolysis giving no buildup of high intermediate
      concentrations were combined. Degradation data of 2,4-D for photocatalysis,
      ozonolysis and the combination of both for different pH ranges are given. Data on
      the main intermediate 2,4-DCP are given for the three different approaches.

PMID- 9532732
TI  - Organic trace compounds in the water of the River Elbe near Hamburg. Part I.
AB  - Water samples of the River Elbe near Hamburg were analyzed for 145 organic
      chemical compounds. In part I results of the investigations concerning the
      following groups of compounds are presented (57 individual compounds): volatile
      chlorinated hydrocarbons, chloroalkylethers (haloethers), chlorobenzenes,
      nitrobenzenes, chloronitrobenzenes, and chloroanilines. Highest concentrations
      were found for the chlorinated bispropylethers and 1,7-dichloro-3,5-dioxaheptane
      (haloethers). Other important compounds were nitrobenzene, nitrotoluenes, and
      chloronitrobenzenes. The results were assessed on the basis of German surface
      water quality criteria.

PMID- 9532734
TI  - Genetic organization and function of the aflatoxin B1 biosynthetic genes.
AB  - Aflatoxins are secondary metabolites produced by Aspergillus flavus and
      Aspergillus parasiticus. Most of the genes involved in the biosynthesis of
      aflatoxin are contained within a single cluster in the genome of these
      filamentous fungi. Studies directed toward understanding the molecular biology of
      aflatoxin biosynthesis have led to a number of important discoveries. A pair of
      fatty acid synthase genes were identified that are involved uniquely in aflatoxin
      biosynthesis. Two genes were also characterized that represent new families of
      cytochrome P450 monooxygenases. Gene expression is coordinated during aflatoxin
      production and is under the control of a positive regulatory gene belonging to a
      family of fungal transcriptional activators associated with various metabolic
      pathways in fungi.

PMID- 9532733
TI  - Organic trace compounds in the water of the River Elbe near Hamburg. Part II.
AB  - Part II of the quantitative determination of altogether 145 distinct organic
      compounds is presented (88 organic compounds). Elevated amounts of some
      pesticides concerning triazines and especially dimethoate were recorded as well
      as of O,O,O-trimethylthiophosphate and O,O,S-trimethyldithiophos-phate, which are
      related to the chemistry of dimethoate. A comparison of the results of PCB
      quantification in unfiltered water samples with the results for solid phase
      material (SPM-phase) in river water is presented. The occurrence of organic trace
      compounds in the River Elbe is discussed in comparison to corresponding
      investigations of the River Rhine.

PMID- 9532735
TI  - Photobactericidal activity of phenothiazinium dyes against methicillin-resistant
      strains of Staphylococcus aureus.
AB  - The photodynamic antibacterial properties of a closely related series of
      phenothiazinium dyes were tested against several pathogenic strains of
      Staphylococcus aureus, four of which were methicillin-resistant. Illumination of
      the photosensitisers at a fluence rate of 1.75 mW cm-2 generally resulted in the
      enhancement of antibacterial activity in liquid culture and in greater efficacy
      than the methicillin analogue flucloxacillin. For methylene blue, dimethyl
      methylene blue and new methylene blue illumination led to increases in
      bactericidal activity < or = 16-fold, typically 4-fold. In addition dimethyl
      methylene blue and new methylene blue were active against epidemic strains of
      methicillin-resistant Staphylococcus aureus at concentrations lower than that of
      vancomycin (> or = 0.5 microM).

PMID- 9532736
TI  - Characterization of a 20-kDa pilus protein expressed by a diarrheogenic strain of
      non-O1/non-O139 Vibrio cholerae.
AB  - A diarrheogenic strain of non-O1/non-O139 Vibrio cholerae (10,325) belonging to
      serogroup O34 was earlier shown to express a new type of pilus composed of a 20
      kDa subunit protein. Amino-terminal sequence data (determined up to 20 amino acid
      residues) of this protein showed it to be different from the subunit proteins of
      other known types of pili of V. cholerae. On the other hand, it showed complete
      homology with the corresponding sequence of a 22-kDa outer membrane protein
      (OmpW) of V. cholerae. Expression of 10,325 pili was favored in AKI rather than
      in NB medium and at 30 degrees C rather than at 37 degrees C. Further, cultural
      conditions favoring pilus expression also enhanced autoagglutination and
      adherence properties of strain 10,325. An antiserum to the 20-kDa protein induced
      passive protection against challenge with the parent organism 10,325, but not
      against V. cholerae O1 strains. Such protection was shown to be mediated by
      inhibition of intestinal colonization in vivo.

PMID- 9532737
TI  - Expression of CDR1, a multidrug resistance gene of Candida albicans:
      transcriptional activation by heat shock, drugs and human steroid hormones.
AB  - We have examined the expression of CDR1 (Candida drug resistance gene) in
      different stress conditions. There was a significant but transient enhancement of
      CDR1 expression associated with elevated temperatures. Most noteworthy
      transcriptional activation was observed with miconazole and vinblastine.
      Interestingly, beta-estradiol and progesterone were also able to enhance CDR1
      expression. Elevated levels of CDR1 and CDR2 (a homologue of CDR1) mRNA were
      found in some azole-resistant clinical isolates of C. albicans. CaMDR1 (benomyl
      resistant) expression, however, did not differ among all the resistant isolates.
      Our results confirm the existence of multiple mechanisms of azole resistance in
      C. albicans.

PMID- 9532738
TI  - A tRNA(Glu) gene from the hyperthermophilic archaeon Pyrococcus furiosus contains
      the 3'-terminal CCA sequence of the mature tRNA.
AB  - We cloned a gene encoding tRNA(Glu) of the hyperthermophilic archaeon Pyrococcus
      furiosus. This gene contains the CCA sequence corresponding to the 3'-terminus of
      the mature tRNA. It is known that, like in eukaryal tRNAs, the CCA-termini of
      archaeal tRNAs are generally not encoded. Therefore, we analyzed all tRNA genes
      in the genome of Methanococcus jannaschii estimated by its whole genome sequence.
      Twenty-one of 37 listed tRNA genes contained the 3'-terminal CCA sequence. The
      corresponding M. jannaschii tRNA(Glu) gene does not contain the CCA sequence,
      although the tRNA sequences of the M. jannaschii and P. furiosus tRNA(Glu) genes
      are 86% identical.

PMID- 9532739
TI  - BstB7SI (R decreases CCGGY), a thermostable isoschizomer of Cfr10I, from a strain
      of Bacillus stearothermophilus isolated from oil-contaminated soil in Kuwait.
AB  - Isolates of thermophilic bacteria from desert soil in Kuwait, heavily
      contaminated with crude oil, have been screened for the presence of restriction
      endonuclease activity. One of the isolates (B7S), identified as Bacillus
      stearothermophilus, showed a high level of restriction endonuclease activity when
      a cell-free extract was incubated with lambda bacteriophage DNA at 65 degrees C.
      A type II restriction endonuclease (BstB7SI) has been partially purified from
      this isolate. BstB7SI recognises the six-base sequence RCCGGY (R = A or G; Y = T
      or C) and hydrolyses the phosphodiester bond in both strands of the DNA substrate
      between the first and second bases of the recognition sequence 5'-R decreases
      CCGGY-3'producing four-base 5' overhangs. BstB7SI is therefore an isoschizomer of
      the mesophilic prototype restriction endonuclease Cfr10I. BstB7SI has a pH
      optimum of 9.7, requires 10 mM MgCl2 and 75 mM NaCl for maximum activity, and
      retains full enzyme activity when incubated for 5 min at temperatures up to 70
      degrees C.

PMID- 9532740
TI  - Chromosome sizes and phylogenetic relationships between serotypes of
      Actinobacillus pleuropneumoniae.
AB  - The genome size of Actinobacillus pleuropneumoniae was determined by pulsed field
      gel electrophoresis of AscI and ApaI digested chromosomal DNA. The genome size of
      the type strain 4074T (serotype 1) was determined to be 2404 +/- 40 kb. The
      chromosome sizes for the reference strains of the other serotypes range between
      2.3 and 2.4 Mb. The restriction pattern profiles of AscI, ApaI and NheI digested
      chromosomes showed a high degree of polymorphism among the different serotype
      reference strains and allowed their discrimination. The analysis of the
      macrorestriction pattern polymorphism revealed phylogenetic relationships between
      the different serotype reference strains which reflect to some extent groups of
      serotypes known to cross-react serologically. In addition, different pulsed
      fields gel electrophoresis patterns also revealed heterogeneity in the
      chromosomal structure among different field strains of serotypes 1, 5a, and 5b,
      while strains of serotype 9 originating from most distant geographical places
      showed homogeneous ApaI patterns in pulsed field gel electrophoresis.

PMID- 9532741
TI  - Extracellular superoxide dismutase from Streptococcus pyogenes type 12 strain is
      manganese-dependent.
AB  - Highly purified extracellular superoxide dismutase was obtained from
      Streptococcus pyogenes strain 12,714 (type 12) by adsorption of culture
      supernatant on phenyl-Sepharose following preparative isoelectric focusing of
      eluates and a final gel filtration purification on Superdex 200. The purified
      superoxide dismutase of S. pyogenes was found to be a homodimer. The monomeric
      protein had a molecular mass of 22,442 Da and an isoelectric point of 4.0. The
      enzymatic activity was strongly manganese-dependent. The N-terminal sequence of
      the purified mature protein was AIILPELPYAYDALEPQUFDA and corresponded to the
      first amino acids following the methionine initiation codon with no evidence of a
      leader sequence for the mature protein. The DNA sequence of the superoxide
      dismutase gene of strain 12,714 was found to be almost identical to the
      corresponding sequences reported in the gene bank data from other S. pyogenes
      serotypes and showed strong homology to superoxide dismutases from other Gram
      positive bacteria.

PMID- 9532742
TI  - The isiB gene encoding flavodoxin is not essential for photoautotrophic iron
      limited growth of the cyanobacterium Synechocystis sp. strain PCC 6803.
AB  - When iron becomes limiting, Synechocystis 6803 induces the synthesis of
      flavodoxin. As a basis for genetic analysis, the flavodoxin-encoding isiB gene of
      Synechocystis 6803 was cloned and sequenced. The isiB gene was disrupted by
      insertion of an interposon within the isiB coding region resulting in two
      Synechocystis 6803 mutant strains, CKF-I and CKF-II. They were distinguished from
      each other by the orientation of the kanamycin resistance cassette.
      Photoautotrophic growth of the mutant strains under iron limiting conditions,
      which are sufficient for induction of flavodoxin in the wild-type cells,
      demonstrated that IsiB was not essential for Synechocystis 6803.

PMID- 9532743
TI  - The deconvolution of pyrolysis mass spectra using genetic programming:
      application to the identification of some Eubacterium species.
AB  - Pyrolysis mass spectrometry was used to produce complex biochemical fingerprints
      of Eubacterium exiguum, E. infirmum, E. tardum and E. timidum. To examine the
      relationship between these organisms the spectra were clustered by canonical
      variates analysis, and four clusters, one for each species, were observed. In an
      earlier study we trained artificial neural networks to identify these clinical
      isolates successfully; however, the information used by the neural network was
      not accessible from this so-called 'black box' technique. To allow the
      deconvolution of such complex spectra (in terms of which masses were important
      for discrimination) it was necessary to develop a system that itself produces
      'rules' that are readily comprehensible. We here exploit the evolutionary
      computational technique of genetic programming; this rapidly and automatically
      produced simple mathematical functions that were also able to classify organisms
      to each of the four bacterial groups correctly and unambiguously. Since the rules
      used only a very limited set of masses, from a search space some 50 orders of
      magnitude greater than the dimensionality actually necessary, visual
      discrimination of the organisms on the basis of these spectral masses alone was
      also then possible.

PMID- 9532744
TI  - Segregation pattern of kanamycin resistance marker in Azotobacter vinelandii did
      not show the constraints expected in a polyploid bacterium.
AB  - It was suggested that Azotobacter vinelandii cells contain about 80 copies of
      their chromosome and when foreign genes are introduced into the cell, it took
      several generations for them to spread to all 80 chromosomes even in the presence
      of selection. In contrast, the fact that many recessive mutants can be isolated
      from A. vinelandii without the constraints expected for a cell that has 80 copies
      of its chromosome argued against this organism being highly polyploid. We have
      investigated the segregation of a kanamycin resistant genetic marker under non
      selective conditions in A. vinelandii. Plasmid DNA was used to introduce the
      kanamycin resistance gene onto the A. vinelandii chromosome at the nifY locus by
      homologous recombination. The transformants were identified from non
      transformants with the aid of replica plating, and hence the colonies examined
      for segregation of the genetic marker were never subjected to kanamycin
      selection. In spite of growing the transformants in the absence of selection
      pressure, no segregant that lacked the kanamycin resistance gene was scored.
      These analyses suggested that the segregation of the kanamycin marker in A.
      vinelandii did not exhibit any constraints expected in a highly polyploid
      bacterium.

PMID- 9532745
TI  - Relationship between presence of Salmonella and indicators of faecal pollution in
      aquatic habitats.
AB  - The presence of Salmonella and its relationship with indicators of faecal
      pollution was investigated in aquatic habitats. The highest frequency was
      obtained in rivers (58.7% of samples) followed by freshwater reservoirs (14.8%)
      and sea water (5.9%). The sporadic presence of Salmonella (< 30%) on beaches with
      low concentrations of faecal streptococci (mean 25 CFU (100 ml)-1) may represent
      a potential risk for bathers in agreement with data found in previous
      epidemiological studies. Absence of Salmonella was observed only on beaches with
      very low densities (CFU (100 ml)-1) of indicator organisms (25 total coliforms,
      13 faecal coliforms and 17 faecal streptococci).

PMID- 9532746
TI  - Adhesive interactions between medically important yeasts and bacteria.
AB  - Yeasts are being increasingly identified as important organisms in human
      infections. Adhesive interactions between yeasts and bacteria may contribute to
      yeast retention at body sites. Methods for studying adhesive interactions between
      bacterial strains are well known, and range from simple macroscopic methods to
      flow chamber systems with complex image analysis capabilities. The adhesive
      interactions between bacteria and yeasts have been studied employing several of
      the methods originally developed for studying adhesive interactions between
      bacteria. However, in many of the methods employed the larger size of the yeasts
      as compared with bacteria results in strong sedimentation of the yeasts, often
      invalidating the method adapted. In addition, most methods are semi-quantitative
      and do not properly control mass transport. Consequently, adhesive interaction
      mechanisms between yeasts and bacteria identified hitherto, including lectin
      binding and protein-protein interactions, must be regarded with caution.
      Extensive physico-chemical characteristics of yeast cell surfaces are not
      available and a physico-chemical mechanism has not yet been put forth. A new
      method for quantifying adhesive interactions between yeasts and bacteria is
      proposed, based on the use of a parallel plate flow chamber, in which the
      influence of adhering bacteria upon the kinetics of yeast adhesion and
      aggregation of the adhering yeasts is quantitatively evaluated, under carefully
      controlled mass transport.

PMID- 9532747
TI  - Rolling-circle plasmids from Bacillus subtilis: complete nucleotide sequences and
      analyses of genes of pTA1015, pTA1040, pTA1050 and pTA1060, and comparisons with
      related plasmids from gram-positive bacteria.
AB  - Most small plasmids of Gram-positive bacteria use the rolling-circle mechanism of
      replication and several of these have been studied in considerable detail at the
      DNA level and for the function of their genes. Although most of the common
      laboratory Bacillus subtilis 168 strains do not contain plasmids, several
      industrial strains and natural soil isolates do contain rolling-circle
      replicating (RCR) plasmids. So far, knowledge about these plasmids was mainly
      limited to: (i) a classification into seven groups, based on size and restriction
      patterns; and (ii) DNA sequences of the replication region of a limited number of
      them. To increase the knowledge, also with respect to other functions specified
      by these plasmids, we have determined the complete DNA sequence of four plasmids,
      representing different groups, and performed computer-assisted and experimental
      analyses on the possible function of their genes. The plasmids analyzed are
      pTA1015 (5.8 kbp), pTA1040 (7.8 kbp), pTA1050 (8.4 kbp), and pTA1060 (8.7 kbp).
      These plasmids have a structural organization similar to most other known RCR
      plasmids. They contain highly related replication functions, both for leading and
      lagging strand synthesis. pTA1015 and pTA1060 contain a mobilization gene
      enabling their conjugative transfer. Strikingly, in addition to the conserved
      replication modules, these plasmids contain unique module(s) with genes which are
      not present on known RCR plasmids of other Gram-positive bacteria. Examples are
      genes encoding a type I signal peptidase and genes encoding proteins belonging to
      the family of response regulator aspartate phosphatases. The latter are likely to
      be involved in the regulation of post-exponential phase processes. The presence
      of these modules on plasmids may reflect an adaptation to the special conditions
      to which the host cells were exposed.

PMID- 9532748
TI  - Written lists as mediating stimuli in the matching-to-sample performances of
      individuals with mental retardation.
AB  - Students with mental retardation learned to write lists in order to perform a
      matching task that they could not do otherwise. After an initial assessment
      phase, reinforcement was arranged in the computerized tasks to follow selection
      of the six pictures that were identical to those in the six-picture samples
      presented. In Study 1, even though the participants wrote a list of the names of
      the six sample pictures on each trial, read a list, or did both, they often made
      errors when a brief delay preceded picture selection. In contrast, performance
      was nearly perfect when a list was written, read, and remained available at the
      time of picture selection, suggesting that the list served to mediate the delays.
      Study 2 examined the stimulus control by two- and six-picture samples over the
      list writing. Early during testing, 1 participant refrained from writing lists on
      two-picture trials but wrote lists on six-picture trials, thereby maximizing
      reinforcement and minimizing its delay; the other participant showed this pattern
      of list writing after supplemental training. The studies suggest methods for
      establishing a rudimentary repertoire of mediating behavior that has relevance
      for teaching instruction-following skills in natural settings.

PMID- 9532750
TI  - Response allocation to concurrent fixed-ratio reinforcement schedules with work
      requirements by adults with mental retardation and typical preschool children.
AB  - The present experiments examined the effect of work requirements in combination
      with reinforcement schedule on the choice behavior of adults with mental
      retardation and preschool children. The work requirements of age-appropriate
      tasks (i.e., sorting silverware, jumping hurdles, tossing beanbags) were
      manipulated. Participants were presented with their choice of two response
      options for each trial that varied simultaneously on both work requirement and
      reinforcement schedule. Results showed that when responding to both choices
      occurred on the same reinforcement schedule, participants allocated most of their
      responses to the option with the easier work requirement. When the response
      option requiring less work was on a leaner reinforcement schedule, most
      participants shifted their choice to exert more work. There were individual
      differences across participants regarding their pattern of responding and when
      they switched from the lesser to the greater work requirement. Data showed that
      participants' responding was largely controlled by the reinforcement received for
      responding to each level of work. Various conceptualizations regarding the
      effects of work requirements on choice behavior are discussed.

PMID- 9532749
TI  - Classification of vowels and consonants by individuals with moderate mental
      retardation: development of arbitrary relations via match-to-sample training with
      compound stimuli.
AB  - This study explored whether an identity-matching-based stimulus equivalence
      procedure could be used to teach vowel and consonant stimulus classes to 2
      adolescent females with moderate mental retardation. Delayed match-to-sample
      trials presented a compound sample stimulus consisting of printed letters and a
      spoken word ("vowel" or "consonant"). The correct comparison stimulus matched
      only one of the letters in the compound sample. Subsequently, test trials
      assessed whether arbitrary relations had formed among the individual stimuli from
      each compound sample and whether stimuli from different compound samples had
      merged into larger stimulus classes. Both participants acquired five-member
      classes of vowel and consonant stimuli, which subsequently generalized to vocal
      classification and to identification in the context of four-letter words. Follow
      up tests showed that the generalized performances remained intact after 6 weeks.
      These procedures suggest an economical approach to stimulus class development.

PMID- 9532751
TI  - Classroom-based functional and adjunctive assessments: proactive approaches to
      intervention selection for adolescents with attention deficit hyperactivity
      disorder.
AB  - The present investigation evaluated the utility of classroom-based functional and
      adjunctive assessments of problem behaviors for 2 adolescents who met diagnostic
      criteria for attention deficit hyperactivity disorder (ADHD) and comorbid
      oppositional defiant disorder (ODD). For children with ADHD-ODD, environmental
      classroom variables, when systematically manipulated by teachers, were related to
      the occurrence and nonoccurrence of problem behaviors. Classroom interventions
      derived from information that was obtained during functional and adjunctive
      assessments and from subsequent analyses resulted in substantial reductions in
      problem behaviors. Teacher and student consumer satisfaction ratings indicated
      that the interventions were effective and feasible in the classroom setting.

PMID- 9532752
TI  - The effect of reinforcer preference on functional analysis outcomes.
AB  - We combined functional analyses and concurrent-schedule assessments to identify
      reinforcer preference during situations in which problem behavior may have been
      multiply controlled. Participants were 3 children with developmental delays who
      engaged in problem behavior during toy play with another child and one adult
      present, suggesting that problem behavior may have been maintained by adult
      attention or access to tangible reinforcement. Thus, conditions were designed to
      test attention and access-to-toys hypotheses. Initial functional analyses
      suggested multiple control. Subsequent concurrent-schedule assessments identified
      preference between the reinforcers, and treatments were based on these findings.
      Findings are discussed regarding the assessment of potentially multiply
      controlled problem behavior.

PMID- 9532753
TI  - Evaluation of a sexual abuse prevention program for adults with mental
      retardation.
AB  - Programs to teach sexual abuse prevention skills to persons with mental
      retardation have rarely been evaluated empirically, and typical evaluations are
      limited to assessment of the participants' knowledge rather than their
      performance of specific skills. In the present study, 6 adult women with mental
      retardation were trained in sexual abuse prevention, and performance was assessed
      using four separate measures: pretests and posttests of knowledge, verbal report,
      role play, and naturalistic probes. All women learned the skills but failed to
      exhibit them to criterion during the probes. We discuss the implications for
      further training and assessment of sexual abuse prevention skills.

PMID- 9532754
TI  - The evaluation and treatment of aggression maintained by attention and automatic
      reinforcement.
AB  - In the current investigation, we used direct and indirect methods to assess and
      treat several topographies of aggression that were hypothesized to have separate
      operant functions in a young boy with severe mental ratardation and pervasive
      developmental disorder. First, a functional analysis of aggression, using the
      methods described by Iwata, Dorsey, Slifer, Bauman, and Richman (1982/1994), was
      conducted and produced inconclusive results. Next, indirect methods were used to
      develop a second functional analysis, which showed that chin grinding (firmly
      pressing and grinding his chin against the skin and bones of others) persisted
      independent of social contingencies and that the other topographies of aggression
      (e.g., hitting, kicking) were maintained by social positive reinforcement
      (attention). A treatment designed to decrease aggression maintained by attention-
      functional communication training with extinction--reduced all forms of
      aggression except chin grinding. This latter topography of aggression, which we
      hypothesized was maintained by automatic reinforcement, was reduced when the
      response--reinforcer relation was interrupted through response blocking and the
      child was provided with an alternative form of chin stimulation.

PMID- 9532756
TI  - Treatment of sleep problems in a toddler: a replication of the faded bedtime with
      response cost protocol.
AB  - Multiple sleep problems of a 2-year-old girl improved following treatment with a
      faded bedtime with response cost procedure (Piazza & Fisher, 1991). These results
      extend the literature by implementing treatment in a home setting with a
      nondisabled child using the parents as therapists.

PMID- 9532755
TI  - The effects of reinforcement rate on the spontaneous social initiations of
      socially withdrawn preschoolers.
AB  - Social skills priming was used to increase the spontaneous social initiations of
      2 socially withdrawn preschoolers, 1 of whom had been diagnosed with autism.
      During priming sessions, the teacher prompted and reinforced social behaviors
      (e.g., smiling, verbal initiations). We varied the rate of reinforcement during
      priming sessions and measured the effects of this manipulation on the rate of
      spontaneous social initiations during the subsequent classroom activity.
      Spontaneous initiations were more frequent after high rates of reinforcement than
      after low rates of reinforcement.

PMID- 9532757
TI  - Evaluating a more cost-efficient alternative to providing in-home feedback to
      parents: the use of spousal feedback.
AB  - We evaluated the contribution of spousal feedback to a parent education
      curriculum designed for parents of children with autism. A modified multiple
      baseline design across 3 husband-and-wife dyads was used to examine the effects
      of teaching parents to give each other feedback on their teaching performance.
      For 5 of 6 participants, improvement in teaching performance occurred following
      didactic presentations. However, additional improvement was observed for 5
      participants when the spousal feedback component was implemented.

PMID- 9532758
TI  - Why behavior analysts should study emotion: the example of anxiety.
AB  - Historically, anxiety has been a dominant subject in mainstream psychology but an
      incidental or even insignificant one in behavior analysis. We discuss several
      reasons for this discrepancy. We follow with a behavior-analytic
      conceptualization of anxiety that could just as easily be applied to emotion in
      general. Its primary points are (a) that languageable humans have an
      extraordinary capacity to derive relations between events and that it is a simple
      matter to show that neutral stimuli can acquire discriminative functions
      indirectly with no direct training; (b) that private events can readily acquire
      discriminative functions; (c) that anxiety disorders seem to occur with little
      apparent direct learning or that the amount of direct learning is extraordinarily
      out of proportion with the amount of responding; and (d) that the primary
      function of anxious behavior is experiential avoidance. We conclude that the most
      interesting aspects of anxiety disorders may occur as a function of derived
      rather than direct relations between public events and overt and private
      responses with avoidance functions. Implicit in this conclusion and explicit in
      the paper is the assertion that anxiety is a suitable subject for behavior
      analytic study.

PMID- 9532759
TI  - Dispersal, philopatry, and genetic relatedness in a social carnivore: comparing
      males and females.
AB  - A balance must be maintained between the proportion of individuals dispersing and
      the proportion remaining philopatric such that inbreeding and resource
      competition are minimized. Yet the relative importance of dispersal and
      philopatric behaviour is uncertain, especially for species with complex social
      systems. We examine the influence of dispersal on genetic relationships of a
      white-nosed coati (Nasua narica: Procyonidae) population from Panama. Field
      studies of the coati indicate a social system in which all females are highly
      philopatric and live in bands while all adult males become solitary at maturity,
      but do not disperse from the home range of their natal band. Based on analyses of
      multilocus DNA fingerprints, we confirm that female philopatry is the rule, long
      distance dispersal is rare, and that relatedness between most bands is low.
      However, some new bands result from fission events and these bands retain
      relatively high relatedness to one another for several years. Adult males
      inhabiting the home range of a band are closely related to band members. In
      contrast, males and band members whose ranges do not overlap are unrelated or
      only slightly related. Adult males are also more closely related to other males
      whose home ranges they overlap extensively than to males whose home ranges they
      overlap only slightly. These results indicate that males initially disperse from
      their natal bands to reduce resource competition and not to avoid inbreeding.
      Inbreeding avoidance, if it occurs, results from more extensive range movements
      by males during the mating season.

PMID- 9532760
TI  - Mitochondrial DNA diversity and historical biogeography of a wet forest
      restricted frog (Litoria pearsoniana) from mid-east Australia.
AB  - MtDNA sequencing was used to investigate the genetic population structure of
      Litoria pearsoniana, a wet forest-restricted hylid frog, endemic to southeast
      Queensland and northeast New South Wales, Australia. L. pearsoniana is regarded
      as endangered under Queensland legislation. Significant genetic divergence among
      populations of frogs from different rainforest isolates was identified, but the
      lack of reciprocal monophyly among adjacent isolates suggests this is the result
      of a relatively recent disruption to gene flow. A paired catchment study within a
      single rainforest isolate, the Conondale Range, revealed no substantial genetic
      structuring, indicating the occurrence of terrestrial dispersal among nearby
      streams either in the recent past or currently. Two major reciprocally
      monophyletic clades of mtDNA alleles were identified. These corresponded to two
      geographical regions separated by the Brisbane River valley; one consisting of
      the Conondale and D'Aguilar Ranges, and the other of the southern isolates in the
      Main, Border and Gibraltar Ranges. Sequence divergence between the two regions
      was more consistent with a late Miocene or Pliocene rather than late Pleistocene
      separation, and is similar to that found among phylogeographic divisions of
      rainforest reptiles and amphibians in north Queensland rainforests. The molecular
      evidence for long-term separation of these two regions is corroborated by the
      pattern of species turnover in the distributions of species of rainforest
      restricted amphibians and reptiles. Bioclimatic modelling suggests that
      appropriate conditions for L. pearsoniana would have been restricted to isolated
      refugees in each phylogeographic division under cooler and drier climates, such
      as predicted for the last glacial maximum. Currently isolated montane areas may
      have been connected transiently during the past 2000 years. Identification of
      long-term zoogeographic divisions among southeast Queensland rainforest
      herpetofauna has important implications for conservation and management.
      Conservation management of L. pearsoniana should be applied at the scale of major
      rainforest isolates and the conservation status of the species should be assessed
      independently north and south of the historical division.

PMID- 9532761
TI  - Population structure of African buffalo inferred from mtDNA sequences and
      microsatellite loci: high variation but low differentiation.
AB  - The African buffalo (Syncerus caffer) is widespread throughout sub-Saharan Africa
      and is found in most major vegetation types, wherever permanent sources of water
      are available, making it physically able to disperse through a wide range of
      habitats. Despite this, the buffalo has been assumed to be strongly philopatric
      and to form large aggregations that remain within separate home ranges with
      little interchange between units, but the level of differentiation within the
      species is unknown. Genetic differences between populations were assessed using
      mitochondrial DNA (control region) sequence data and analysis of variation at six
      microsatellite loci among 11 localities in eastern and southern Africa. High
      levels of genetic variability were found, suggesting that reported severe
      population bottlenecks due to outbreak of rinderpest during the last century did
      not strongly reduce the genetic variability within the species. The high level of
      genetic variation within the species was found to be evenly distributed among
      populations and only at the continental level were we able to consistently detect
      significant differentiation, contrasting with the assumed philopatric behaviour
      of the buffalo. Results of mtDNA and microsatellite data were found to be
      congruent, disagreeing with the alleged male-biased dispersal. We propose that
      the observed pattern of the distribution of genetic variation between buffalo
      populations at the regional level can be caused by fragmentation of a previous
      panmictic population due to human activity, and at the continental level,
      reflects an effect of geographical distance between populations.

PMID- 9532762
TI  - Recent divergence between two morphologically differentiated subspecies of
      bluethroat (Aves: Muscicapidae: Luscinia svecica) inferred from mitochondrial DNA
      sequence variation.
AB  - We assessed the mitochondrial DNA sequence divergence of a 718 bp fragment of the
      control region and 1007 bp of the cytochrome b gene between two allopatric
      morphologically different subspecies of bluethroat (Luscinia svecica). None of
      the 17 total haplotypes was shared between L. s. namnetum and L. s. svecica.
      However, the mean distances between subspecies were very low for both fragments
      (0.00168 +/- 0.00001 (mean +/- SE) for the control region; 0.00306 +/- 0.00016
      for the cytochrome b gene). Only one substitution made the two subspecies
      genetically differentiated, highlighting their recent divergence. Interestingly,
      the control region was not more variable than the cytochrome b gene.

PMID- 9532764
TI  - Development of microsatellite markers for parentage typing of chicks in the
      ostrich Struthio camelus.

PMID- 9532763
TI  - Microsatellite markers in wood mouse and striped field mouse (genus Apodemus).

PMID- 9532766
TI  - Primers for polymorphic GT microsatellites isolated from the Mariana crow, Corvus
      kubaryi.

PMID- 9532765
TI  - Isolation and characterization of microsatellite loci in the seed chalcid
      Megastigmus wachtli (Hymenoptera).

PMID- 9532767
TI  - Lives in the balance.

PMID- 9532768
TI  - Clock setting.

PMID- 9532769
TI  - Not what the doctor ordered.

PMID- 9532770
TI  - Post-polio syndrome.

PMID- 9532771
TI  - Laser scissors and tweezers.

PMID- 9532772
TI  - Correlation between dynamics, structure and spectral properties of human alpha 1
      acid glycoprotein (orosomucoid): a fluorescence approach.
AB  - Dynamics of proteins and membranes are usually investigated by red-edge
      excitation spectra and fluorescence anisotropy. In a viscous or rigid medium, the
      fluorescence maximum position changes with the excitation wavelength upon red
      edge excitation. In addition to the shift in the emission maximum on red edge
      excitation, fluorescence anisotropy is also known to be dependent on the
      excitation and emission wavelengths in viscous media. However, this dependence
      has always been explained by the fact that the fluorophore is rigid, i.e. it does
      not display any residual motions. The aim of the present work was to check the
      validity of this latest assumption and to explain the possible origin of the
      dependence of the anisotropy on both the excitation and emission wavelengths.
      Therefore, we compared the results obtained from the fluorescence of the Trp
      residues of two alpha 1-acid glycoproteins (orosomucoid). One protein was
      purified by chromatographic methods (orosomucoid(c)) and the other was obtained
      with ammonium sulfate precipitation (orosomucoid(s)). Trp residues of
      orosomucoidc display free motions while those of orosomucoids are rigid. The
      general qualitative feature of the excitation anisotropy spectra recorded on both
      types of preparation is identical and resembles that obtained for other proteins
      containing tryptophan residue in protein. The fluorescence anisotropy measured
      across the emission spectra decreases for both preparations, indicating that this
      phenomenon is characteristic for fluorophores surrounded by a rigid
      microenvironment or by a microenvironment that displays motions. The fluorescence
      anisotropy variation across the emission and the excitation spectra is more
      important when the fluorophore possesses constrained motions than when it
      displays a high degree of freedom. Our results clearly demonstrate that the
      tertiary structure of the protein and the structure and dynamics of the
      microenvironments of the Trp residues are the origin of the dependence of
      anisotropy on the excitation and emission wavelengths.

PMID- 9532773
TI  - FT-IR and X-ray spectroscopic investigations of Na-diclofenac-cyclodextrins
      interactions.
AB  - The association of DCF-Na (the salt of the 2-[(2,6-dichlorophenyl)amino]-phenyl
      acetic acid) with beta-CD (cyclodextrin) in some therapeutic formulas can
      contribute to the optimisation of the physico-chemical and pharmaceutical
      properties of the parent drug. The understanding of the interaction between DCF
      with beta-CD represents the objective of this study. FT-IR spectroscopy is one of
      the methods which clarify the nature of these interactions in complexes of such
      type. Therefore the changes in FT-IR spectra of binary dispersed systems DCF/beta
      CD in physical mixture and coprecipitate from methanol (molar ratios: 1/1, 1/2,
      2/3, 3/4, 7/4) were analysed. The analysis of the broadening of the X-ray powder
      diffraction line has been applied to investigate the average effective
      crystallite size, the mean square of the microstrain caused by distortions within
      beta-CD crystallite and the fault probability in the binary dispersed DCF/beta-CD
      coprecipitate system.

PMID- 9532774
TI  - Effects of lactic acid bacteria on binding and absorption of mutagenic
      heterocyclic amines.
AB  - Effects of binding heterocyclic amines to cells of lactic acid bacteria on theirs
      absorption were investigated. Cells of Lactobacillus delbrueckii subsp.
      bulgaricus 2038 and Streptococcus thermophilus 1131 bind both 3-amino-1,4
      dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) and 2-amino-3,8-dimethylimidazo[4,5
      f]quinoxaline (MeIQx). The binding of strain 1131 cells to Trp-P-1 was maximum in
      the pHs from 4 to 8, but strain 2038 cells bound Trp-P-1 and MeIQx only slightly
      at pH 7. We investigated the absorption of heterocyclic amines by the small
      intestine of F344 rats in the presence of these bacterial cells, using an in situ
      loop technique. The absorption of Trp-P-1 by the small intestine was
      significantly lower in the presence of strain 1131 cells than in the absence of
      the cells, but the presence of strain 2038 cells had no effect on Trp-P-1
      absorption. Perhaps strain 1131 cells bind to Trp-P-1 at the same pH as that of
      the small intestine (pH 6-7) and thus decrease its absorption.

PMID- 9532775
TI  - Antioxidative activity of carp blood plasma on lipid peroxidation.
AB  - Antioxidative activity of carp blood plasma was estimated by measuring
      hydroperoxides formed by liposome peroxidation during the exposure of liposomes
      to AAPH. Ascorbic acid of high concentration, uric acid of low content, and
      tocopherol formed special protective system against lipid poroxidation in fish
      plasma. The decrease of uric acid, ascorbic acid, and tocopherol showed synergism
      of ascorbic acid and tocopherol, uric acid, and tocopherol. Carp blood plasma
      with a low concentration of protein (about 2%) and SH groups (88 microM) had a
      great effect on the antioxidative activity, as the effects of ascorbic acid, uric
      acid, and tocopherol were dramatically extended. Dialysed carp protein also
      displayed a very strong antioxidative activity on lipid peroxidation of a
      multilayer liposome system.

PMID- 9532776
TI  - Antioxidative activities of several marine polysaccharides evaluated in a
      phosphatidylcholine-liposomal suspension and organic solvents.
AB  - The antioxidative activities of several water-soluble marine polysaccharides,
      alginate (ALG), alginate sulfate (SALG), propylene glucolalginate sodium sulfate
      (PSS), propylene glucol mannuronate sulfate (PGMS), the oligosaccharide of
      chitosan (OLC), N,O-carboxymethyl chitosan (NOCC) and hydroxypropylated chitosan
      (HPC), were examined in a phosphatidylcholine (PC)-liposomal suspension
      containing the water-soluble radical emitter, 2,2'-azobis (2-amidinopropane)
      dihydrochloride. In the suspensions containing OLC and SALG, the initial rates of
      PC-OOH accumulation were 2.78 x 10(-8) MS-1 and 2.88 x 10(-8) MS-1, respectively,
      while all the polysaccharides tested showed antioxidative activity. Liposoluble
      marine polysaccharides, hexanoyl chitin (HCH) and an N-benzoylhexanoyl chitosan
      (NBHC) solution, also retarded the hydroperoxide accumulation of methyl linoleate
      by effectively trapping peroxide radicals in organic solvents when the radical
      chain reaction had been initiated by 2,2'-azobis (2,4-dimethylvaleronitrile). The
      kinetic data presented indicate that the alginate and chitin derivatives can be
      expected to play a role in the antioxidative mechanism of biological systems.

PMID- 9532777
TI  - Mass production of bacterial alpha 2,6-sialyltransferase and enzymatic syntheses
      of sialyloligosaccharides.
AB  - To supply alpha 2,6-sialyltransferase for the large-scale synthesis of sialoside,
      we investigated culture conditions for the production of sialyltransferase 0160.
      The addition of galactose and beef extract, and control of the pH of the culture
      medium were effective on the production of sialyltransferase 0160. The maximal
      enzyme productivity reached 550 units/L. Using a crude extract of Photobacterium
      damsela JT0160 cells as an enzyme source, enzymatic syntheses were performed with
      mono- and di-saccharides as the sialyl acceptors. It was clarified that a crude
      extract of P. damsela JT0160 cells can be used as an synthetic catalyst for the
      enzymatic synthesis of sialyloligosaccharides. Furthermore, the enzyme assay
      showed that sialyltransferase 0160 could transfer NeuAc to not only N-linked but
      also O-linked carbohydrate chains. These results indicated that an abundant
      supply of sialyltransferase 0160 and its broad specificity make possible the
      synthesis of sialoside on a large scale.

PMID- 9532779
TI  - Enzymatic synthesis of a new derivative of thiamin, O-alpha-glucosylthiamin.
AB  - A new transglucosylated derivative of thiamin could be synthesized by the actions
      of cyclomaltodextrin glucanotransferase from Bacillus stearothermophilus and
      glucoamylase from Rhizopus sp., in this order, on a mixture of dextrin and
      thiamin. The derivative was isolated in crystalline form and identified as 5'-O
      (alpha-D-glucopyranosyl)thiamin by spectroscopy (FAB-MS, UV, 1H-NMR, and 13C
      NMR), thiochrome formation with K3 [Fe(CN)6]-NaOH reagent, and the hydrolysis
      products by alpha- and beta-glucosidases. O-alpha-Glucosylthiamin was odorless
      and mildly sweet with no tongue-pricking taste, and was more stable than thiamin
      hydrochloride in aqueous solutions at pHs 7.0 and 9.3.

PMID- 9532778
TI  - Evidence for structural differences between the two highly homologous actin
      regulatory proteins, destrin and cofilin.
AB  - The amino acid sequences of destrin and cofilin are very similar (84% homology)
      throughout the entire range of proteins, but they have different functions. In
      this study, we constructed a new cofilin expression plasmid, which had high
      expression frequency, and the structures of destrin and cofilin were analyzed by
      limited proteolysis and circular dichroism (CD). When destrin was digested by
      trypsin, two fragments of 17.0 kDa and 9.2 kDa were obtained, whereas only one
      8.4 kDa fragment was obtained from cofilin. In spite of the overall sequence
      homology, an N-terminal amino acid sequence analyses of the fragments revealed
      the cleavage sites on destrin and cofilin to be different. These results suggest
      that destrin and cofilin differ in their overall tertiary folds. Cofilin showed
      activity similar to destrin at high pH values, although no pH-dependent
      structural change in cofilin was confirmed by using limited proteolysis and CD.

PMID- 9532780
TI  - Structure of genes for cecropin A and an inducible nuclear protein that binds to
      the promoter region of the genes from the silkworm, Bombyx mori.
AB  - Cecropins are a family of antibacterial peptide synthesized in insects as a
      response to bacterial infection. To study the regulation of the immune genes in
      insects, two cecropin A genes were cloned and sequenced from the silkworm, Bombyx
      mori. The two genes, CecA1 and CecA2, encoded identical preprocecropin A, having
      one intron of 609 bp and 929 bp, respectively. The 5'-upstream regions of the
      genes contained a NF-kappa B like element and IL-6-RE Type I element.
      Electrophoretic mobility shift assay revealed that a nuclear protein of fat body
      which specifically bound to the kappa B-like element was activated by injection
      of the larvae with peptidoglycan.

PMID- 9532781
TI  - Enzymatic properties of a Ginkgo biloba endo-beta-N-acetylglucosaminidase and N
      glycan structures of storage glycoproteins in the seeds.
AB  - An endo-beta-N-acetylglucosaminidase has been purified to homogeneity from mature
      seeds of Ginkgo biloba. The molecular mass of the endo-beta-N
      acetylglucosaminidase, named Endo-GB, was estimated to be around 63 kDa by SDS
      PAGE and around 62 kDa by Hiprep S-200 chromatography, respectively. The
      substrate specificity has been explored with regard to the pyridylaminated N
      glycans. Several high mannose-type sugar chains bearing alpha-1,2-mannosyl
      residue(s), Man9-6GlcNAc2-PA, were the most favored substrates followed by
      Man5GlcNAc2-PA and a typical hybrid-type structure (GlcNAc1Man5Glc NAc2-PA) which
      does not bear an alpha-1,2-mannosyl residue. On the contrary, endo-GB could
      hardly hydrolyze the common core pentasaccharide of N-glycan (Man3GlcNAc2-PA) and
      the xylose-containing sugar chains (Man4-3Xyl1Glc NAc2-PA, Man3Fuc1Xyl1GlcNAc2
      PA) being widely distributed in plant glycoproteins. Furthermore, we analyzed the
      structures of N-glycans conjugated to storage glycoproteins in the mature Ginkgo
      seeds to see the occurrence of endogenous substrates for Endo-GB. The structural
      analysis showed, however, only xylose-containing type N-glycans
      (Man3Fuc1Xyl1GlcNAc2 (95%) and Man3Xyl1 GlcNAc2 (5%)), which can not be substrate
      for Endo-GB, predominantly occur in the storage glycoproteins.

PMID- 9532782
TI  - A cysteine-dependent serine protease associated with the dormant spores of
      Bacillus cereus: purification of the protein and cloning of the corresponding
      gene.
AB  - Subtilisin-like serine protease, which is associated with the dormant spores of
      Bacillus cereus, was solubilized by washing the spores with 2 M KCl and purified
      to homogeneity by carbobenzoxy-D-phenylalanine-liganded affinity column
      chromatography and hydrophobic interaction column chromatography. Enzyme activity
      was completely inhibited by reagents for sulfhydryl groups such as HgCl2 as well
      as by conventional subtilisin inhibitors, suggesting the enzyme to be cysteine
      dependent. The enzyme retained activity in 5 M urea at 4 degrees C for at least 2
      months, and the specific activity was 50 times that of subtilisin BPN when
      measured for a common chromogenic substrate, carbobenzoxy-glycyl-glycyl-L-leucine
      p-nitroanilide. The gene encoding this protease was cloned in Escherichia coli,
      and its nucleotide sequence was analyzed. The deduced amino acid sequence
      suggested that the protease is produced as a precursor comprising three portions;
      a signal sequence (28 amino acid residues), a prosequence (80 amino acid
      residues) and a mature enzyme (289 amino acid residues). The mature region of the
      enzyme had high similarity with a thermitase from Thermoactinomyces vulgaris (72%
      identity) and a thermostable alkaline protease from Thermoactinomyces sp. E79
      (66% identity), which have the N-terminal sequence showing scarcely noticeable
      similarity with corresponding stretches of subtilisins and mercuric ion-sensitive
      free cysteine in the equivalent position of the primary structure.

PMID- 9532783
TI  - Purification and characterization of NADPH-dependent carbonyl reductase, involved
      in stereoselective reduction of ethyl 4-chloro-3-oxobutanoate, from Candida
      magnoliae.
AB  - A NADPH-dependent carbonyl reductase was purified to homogeneity from Candida
      magnoliae AKU4643 through four steps, including Blue Sepharose affinity
      chromatography. The enzyme catalyzed the stereoselective reduction of ethyl 4
      chloro-3-oxobutanoate to the corresponding (S)-alcohol with a 100% enantiomeric
      excess, which is a useful chiral building block for the chemical synthesis of
      pharmaceuticals. The relative molecular mass of the enzyme was estimated to be
      76,000 on high performance gel filtration chromatography and 32,000 on SDS
      polyacrylamide gel electrophoresis. The enzyme reduced alpha-, beta-keto esters
      and conjugated diketones in addition to ethyl 4-chloro-3-oxobutanoate. The enzyme
      activity was inhibited by quercetin and HgCl2, but not by EDTA. The N-terminal
      amino acid sequence of the enzyme showed no apparent similarity with those of
      other oxidoreductases.

PMID- 9532785
TI  - Solubilization and chemical characterization of an insoluble matrix protein in
      the gastroliths of a crayfish, Procambarus clarkii.
AB  - The gastrolith of the crayfish Procambarus clarkii contains a small amount of an
      organic matrix that is mainly chitin and proteins, together with a large amount
      of calcium carbonate. As the first step to understand the mechanism of
      calcification, we tried to characterize matrix proteins in the gastrolith. An
      insoluble matrix protein, referred to as gastrolith matrix protein, was made
      soluble with 1% SDS containing 10 mM dithiothreitol, and was purified by reverse
      phase high-performance liquid chromatography. The protein had a molecular weight
      of about 50,500 and a blocked amino terminus. By enzymatic digestion and
      microsequencing, five partial amino acid sequences with a total of 225 amino acid
      residues were identified and found to include a repetitive sequence not reported
      previously.

PMID- 9532784
TI  - Identification of the promoter region and the transcriptional regulatory sequence
      of the evgAS operon of Escherichia coli.
AB  - The evgAS operon of Escherichia coli encodes the EvgA response regulator and the
      EvgS sensory kinase, which are members of one of the two-component signal
      transduction systems of Escherichia coli. In this study, we identified the evg
      promoter and the EvgA-responsive element. Primer extension analysis found two evg
      transcriptional initiation sites, designated P1 (+1) and P2 (-10), and placed
      them 114 bp and 124 bp upstream of evgA, respectively. A gel retardation assay
      demonstrated that EvgA specifically bound to an inverted repeat located between 
      102 and -128 counting from P1. We also did a beta-galactosidase induction
      experiment using a promoter-probing vector and found that the EvgA-binding
      sequence was important to stimulate the evg promoter. These results suggest that
      the expression of evgAS is positively regulated by its own product, EvgA.

PMID- 9532786
TI  - Non-thermal effect of a ceramics radiation on a yeast glucose-6-phosphate
      dehydrogenase.
AB  - Non-thermal effect of a ceramics radiation on glucose-6-phosphate dehydrogenase
      has been investigated using the enzyme, glucose-6-phosphate and NADP+ separately
      irradiated at 10 degrees C by a ceracompo R plate and a ceramics un-sewed cloth
      (sheet). The Km for glucose-6-phosphate was increased 20% after 6 h of
      irradiation by the plate, but the Vmax/Km was decreased 24%. After 3 h of
      irradiation by the sheet, the Km was increased 17%, but after 6 h of irradiation
      it was decreased 11%. The 3 h of irradiation by the sheet slightly increased both
      enthalpy and entropy changes of the reaction, but the 6 h of irradiation
      significantly decreased them. Both thermodynamic parameters in the activated
      state were increased by the sheet irradiation. The promotion energy for both
      formations of the enzyme-substrate and their activated complex depended on
      enthalpy. The different effects of two ceramics radiators on G6PDH activity were
      discussed.

PMID- 9532787
TI  - Purification and properties of an amylopullulanase, a glucoamylase, and an alpha
      glucosidase in the amylolytic enzyme system of Thermoanaerobacterium
      thermosaccharolyticum.
AB  - Thermoanaerobic bacteria are of considerable interest as producers of
      thermostable amylolytic enzymes. The soluble amylolytic enzyme system of
      Thermoanaerobacterium thermosaccharolyticum DSM 571 was fractionated into a
      pullulanase, a glucoamylase, and an alpha-glucosidase. The enzymes were purified
      to homogeneity and their physical and catalytic properties were studied. The
      pullulanase, which cleaved both alpha-1,4- and alpha-1,6-glucosidic bonds, was an
      amylopullulanase closely related to similar enzymes from other thermoanaerobic
      bacteria. Partial amino acid sequences of the glucoamylase were identical with
      the corresponding sequences deduced from the cga gene encoding the glucoamylase
      from Clostridium sp. strain G0005. The alpha-glucosidase was identified as an
      isomaltase belonging to a group of structurally related exo-alpha-1,4
      glucosidases and oligo-1,6-glucosidases from bacilli. Comparison of enzyme
      activities indicated that the glucoamylase had the major amylolytic activity of
      T. thermosaccharolyticum, with amylopullulanase and alpha-glucosidase assisting
      in the cleavage of alpha-1,6-glucosidic bonds.

PMID- 9532788
TI  - Overproduction of 1,2-alpha-mannosidase, a glycochain processing enzyme, by
      Aspergillus oryzae.
AB  - A recombinant strain of Aspergillus oryzae has been constructed in which 1,2
      alpha-mannosidase, an intracellular glycochain processing enzyme with specificity
      toward 1,2-alpha-mannosidic linkages, has been overexpressed. For the
      construction, the N-terminal signal-encoding sequence of the 1,2-alpha
      mannosidase gene (msdC) from Penicillium citrinum was replaced with that of the
      aspergillopepsin I signal, and the fused gene was inserted between amyB promoter
      terminator elements in the expression plasmid pTAPM1. A transformant of A. oryzae
      (the strain PM-1) secreted a great deal of heterogeneous 1,2-alpha-mannosidase
      into the culture media, which was purified by CM ion-exchange chromatography.
      Approximately 21 mg of the purified enzyme was obtained per liter of culture. N
      terminal amino acid analysis indicated that the signal peptide was removed from
      the secreted enzyme. The Penicillium 1,2-alpha-mannosidase expressed in A. oryzae
      did not show any notable difference from the enzyme from P. citrinum in such
      properties as M(r), specific activity, CD spectra, or kinetic parameters.
      Man7GlcNAc2 accumulated temporarily during the degradation of Man9GlcNAc2 to
      Man5GlcNAc2 by fungal 1,2-alpha-mannosidase.

PMID- 9532789
TI  - Reptile lysozyme: the complete amino acid sequence of soft-shelled turtle
      lysozyme and its activity.
AB  - Soft-shelled turtle egg-white lysozyme was purified and sequenced. Lysozyme was
      reduced and carboxymethylated to fragment it with trypsin, V8 protease and CNBr.
      The peptides yielded were purified by RP-HPLC and sequenced. Every trypsin
      peptide was overlapped by V8 protease peptides and CNBr fragment. The amino acid
      sequence was compared with other lysozymes. This lysozyme has an extra Gly
      residue at N-terminus, which was found in pheasant lysozyme. Further, this
      lysozyme has an insertion of a Gly residue between 47 and 48 residues when
      compared with chicken lysozyme, as found in human lysozyme, therefore it proved
      that this lysozyme has the largest number of amino acids (131 aa) in chicken type
      lysozymes. The amino acid substitutions were found at subsites E and F. Namely
      Phe34, Arg45, Thr47, and Arg114 were replaced by His, Tyr, Arg, and Tyr,
      respectively. The time course using N-acetylglucosamine pentamer as a substrate
      showed a reduction of the rate constant for glycosidic cleavage and increase of
      binding free energy for subsites E and F, which proved the contribution of amino
      acids mentioned above for substrate binding at subsites E and F.

PMID- 9532790
TI  - Diisopropylfluorophosphate (DFP) inhibits ricin-induced apoptosis of MDCK cells.
AB  - Diisopropylfluorophosphate (DFP), a general serine protease inhibitor, inhibited
      the DNA fragmentation and cell death in MDCK cells treated with ricin, modeccin,
      Pseudomonas toxin, or diphtheria toxin. A trypsin-like serine protease inhibitor,
      N-tosyl-L-lysine chloromethyl ketone (TLCK) also prevented ricin-induced DNA
      fragmentation and cell death, albeit less effectively than DFP. Microscopic
      observation showed that the morphological changes of MDCK cells induced by ricin
      were prevented by DFP. DFP did not affect the binding, internalization, or
      subsequent excretion of ricin, but reduced the degradation of ricin in MDCK
      cells, suggesting that DFP inhibits at least the cellular protease that may be
      involved in the degradation of internalized ricin. In addition, SDS-PAGE analysis
      of cytosolic proteins suggested that DFP-sensitive endogenous proteases are
      activated in the ricin-treated cells. In the cells treated with DFP, the protein
      synthesis inhibitory activity of ricin was increased rather than inhibited. The
      activities of modeccin and Pseudomonas toxin were also slightly increased by DFP,
      but no effect of DFP on the activity of diphtheria toxin was observed. Therefore,
      these results suggest that protein toxins have a DFP-sensitive common pathway
      leading to apoptosis that is distinct from the pathway leading to the inhibition
      of cellular protein synthesis.

PMID- 9532791
TI  - Trehalose as osmoprotectant in Rhodobacter sphaeroides f. sp. denitrificans
      IL106.
AB  - The photosynthetic bacterium Rhodobacter sphaeroides f. sp. denitrificans IL106
      can grow in high osmolarity. The accumulation of intracellular inorganic ions and
      organic solutes in cells grown in a synthetic medium containing different
      concentrations of NaCl was examined. Together with potassium ion, trehalose was
      the major organic osmoprotectant and its accumulation depended on the external
      salt concentration. Intracellular levels of glycine betaine and other
      osmoprotectants such as proline did not change when osmolarity increased.

PMID- 9532792
TI  - Two peaks in pH dependence of renin-angiotensinogen reaction.
AB  - The pH dependence of the reaction of purified recombinant human renin with
      purified recombinant sheep angiotensinogen was not a typical bell-shape but had
      two peaks, pH 6.4 and 8.9. The pH dependence of the reaction of human renin with
      human, hog, and rat angiotensinogens partially purified from plasma had a peak
      with a shoulder containing two peaks close together. These findings indicate that
      the reaction of renin with angiotensinogen involves at least two amino acid
      residues other than the two aspartic acid residues known to be involved and
      occurs at acidic pH and basic pH by two different pairs of these amino acid
      residues.

PMID- 9532793
TI  - Molecular cloning and expression of a gene encoding a novel sorbitol oxidase from
      Streptomyces sp. H-7775.
AB  - A gene encoding a novel intracellular sorbitol oxidase of a soil bacterium,
      Streptomyces sp. H-7775, was cloned and sequenced. The gene consists of an open
      reading frame of 1,260-bp encoding a protein of 420 amino acids with a molecular
      weight of 45,148. Deduced amino acid sequence of the gene has 25.3% identity and
      68.1% similarity to that of rat L-gulonolactone oxidase at the overall amino
      acids. Nucleotide-binding motifs were not found in the deduced amino acid
      sequence of SOX protein. We succeeded in expressing recombinant sorbitol oxidase
      with covalently bound FAD in E. coli at about a 4,000-fold higher total enzyme
      activity than that of the Streptomyces sp. H-7775. The enzymatic properties of
      the recombinant SOX were similar to those of the enzyme from Streptomyces sp. H
      7775. This is the first report of the cloning and expression of a newly
      categorized enzyme, sorbitol oxidase, from Streptomyces sp.

PMID- 9532794
TI  - Molecular properties and activity of amino-terminal truncated forms of lipase
      activator protein.
AB  - Two mutant forms, which had truncated N-terminals, of lipase activator protein
      (LipB) from Pseudomonas aeruginosa TE3285 were prepared, and their molecular
      properties and activity were compared with those of the full-length form. A
      truncated LipB lacking its hydrophobic N-terminal 21 residues was dispersed
      homogeneously in solution, and could reactivate the stoichiometric amount of
      denatured lipase. In contrast, full-length LipB formed soluble aggregates, and
      reactivated less than an equimolar amount of the lipase even under the most
      suitable conditions. These findings suggest that some or all of the N-terminal 21
      residues caused aggregation of the protein molecules, and prevented LipB from
      fully stoichiometric reactivation. A truncated LipB lacking the N-terminal 61
      residues also reactivated denatured lipase, suggesting that the N-terminal 61
      residue region of LipB is not involved in reactivation.

PMID- 9532795
TI  - Cloning genomic DNA encoding apple polyphenol oxidase and comparison of the gene
      product in Escherichia coli and in apple.
AB  - Two PCR-amplified genomic DNA fragments encoding apple (cv. Fuji) polyphenol
      oxidase (PPO) were cloned and sequenced. A comparison of genomic DNA with cDNAs
      revealed that the PPOs lacked introns. Both PPO DNAs appear to encode a 66-kDa
      precursor protein consisting of a 56-kDa mature protein and a N-terminal transit
      peptide of 10-kDa N-terminal transit peptide. Apple PPO DNA was expressed in
      Escherichia coli, and the gene product (56 kDa) without a transit peptide was
      immunochemically detected and was the same size (ca. 65 kDa) as the main PPO of
      apple fruit by SDS-PAGE.

PMID- 9532796
TI  - 6-Methylsulfinylhexyl isothiocyanate and its homologues as food-originated
      compounds with antibacterial activity against Escherichia coli and Staphylococcus
      aureus.
AB  - Cruciferae plants, banana and coriander each showed antibacterial activity. The
      highest activity among the food-stuffs tested was found in the stems of wasabi.
      An ethereal extract from wasabi stems had potent antibacterial activity and we
      isolated the active compound from the extract. Instrumental analysis identified
      the compound as 6-methylsulfinylhexyl isothiocyanate. Some homologues of 6
      methylsulfinylhexyl isothiocyanate were also active against Escherichia coli and
      Staphylococcus aureus.

PMID- 9532797
TI  - Effects of germinated barley foodstuff in preventing diarrhea and forming normal
      feces in ceco-colectomized rats.
AB  - Germinated barley foodstuff (GBF) derived from the aleurone and scutellum
      fractions of germinated barley was rich in glutamine and low-lignified
      hemicellulose. The diarrhea caused by ceco-colectomy could be prevented by
      feeding GBF to rats. GBF could also increase the protein content and sucrase
      activity of small intestinal mucosa in this model. This diarrhea-preventive
      effect of GBF would be based on the water-holding capacity and bulging force
      under alkaline conditions, e.g. in the small intestine.

PMID- 9532798
TI  - Overproduction and substrate specificity of 3-isopropylmalate dehydrogenase from
      Thiobacillus ferrooxidans.
AB  - We constructed an overexpression system in Escherichia coli of the leuB gene
      coding for 3-isopropylmalate dehydrogenase in Thiobacillus ferrooxidans. E. coli
      harboring the plasmid we constructed, pKK leuB1, produced 17-fold the enzyme
      protein of the expression system previously used for purification. The substrate
      specificity of the enzyme was analyzed with synthetic (2R, 3S)-3-alkylmalates.
      The 3-isopropylmalate dehydrogenase of Thiobacillus ferrooxidans had broad
      specificity toward the alkylmalates.

PMID- 9532800
TI  - Detection of potato virus Y P1 protein in infected cells and analysis of its
      cleavage site.
AB  - The P1 protein is liberated from the N-terminal region of the potyviral
      polyprotein by cleavage depending on its own autoproteolytic activity. Existence
      of the 32-kDa P1 protein in tobacco plants infected with potato virus Y ordinary
      strain (PVY-O) was detected by an antiserum against a recombinant PVY-O P1
      protein. In vivo analysis using tobacco protoplasts confirmed that the Phe284
      Ser285 was the cleavage site separating the P1 protein from the PVY-O
      polyprotein. Phe284 was indispensable for proteolysis and Ser285 was needed for
      optimal cleavage susceptibility.

PMID- 9532799
TI  - Detection of antitumor promoting activity in Raji cells carrying Epstein-Barr
      virus genome by immunoblotting analysis.
AB  - Extract of Raji cells treated with sodium n-butyrate (1 mM) and a tumor promoter,
      12-O-tetradecanoylphorbol-13-acetate (TPA, 40 ng/ml), was analyzed by
      immunoblotting using ten human sera with different antibody titers against
      Epstein-Barr virus early antigens. Two human sera reacted with one induced
      polypeptide of 48 kDa and its induction was inhibited by curcumin (4
      micrograms/ml), an antitumor promoter from turmeric. A mouse antiserum against
      P3HR-1 cells treated with TPA and sodium n-butyrate also detected the 48-kDa
      polypeptide in Raji cells treated with TPA at concentrations of 2.5 to 80 ng/ml.
      These results indicate that the immunoblotting analysis can be used in a
      confirmation test for detection of antitumor promoting activity.

PMID- 9532801
TI  - Identification of the aspartic acid residue located at or near substrate-binding
      site of rye seed chitinase-c.
AB  - Carboxyl groups of rye seed chitinase-c (RSC-c) were modified with 1-ethyl-3-(3
      dimethylaminopropyl)carbodiimide (EDC) and glycine ethyl ester (GEE) at pH 5.5
      and 5 degrees C in the presence and absence of (GlcNAc)4. In the absence of
      (GlcNAc)4, 5.2 carboxyl groups were modified by 90 min-reaction and the chitinase
      activity was reduced to 2.0%, while in the presence of (GlcNAc)4, 4.6 carboxyl
      groups were modified and 72% of the activity was retained. To identify the
      carboxyl group protected by (GlcNAc)4 from the modification, RSC-c was first
      modified with EDC and GEE in the presence of (GlcNAc)4 and then radiolabeled with
      EDC and [14C]GEE in the absence of (GlcNAc)4. Analyses of the radioactive
      peptides from the tryptic and chymotryptic digests of radiolabeled RSC-c showed
      that the main radiolabeled carboxyl group is that of Asp95, suggesting that Asp95
      is located at or near substrate-binding site of RSC-c.

PMID- 9532802
TI  - Complete amino acid sequence of chitinase-a from bulbs of gladiolus (Gladiolus
      gandavensis).
AB  - The complete amino acid sequence of gladiolus bulb chitinase-a (GBC-a) was
      determined. First the tryptic peptides from GBC-a after it was reduced and S
      carboxymethylated were sequenced and then the peptides were further studied by
      chemical cleavage of the enzyme. GBC-a consisted of 274 amino acid residues and
      had a molecular mass of 30,714 Da. Two consensus sequences essential for
      chitinase activity by plant class III chitinases were conserved in GBC-a,
      although its sequence similarity with plant class III chitinases was less than
      20%. Sequence comparison of GBC-a with sequences of other proteins in a protein
      identification resource (PIR) showed that the GBC-a sequence was 33% similar to
      that of narbonin, a seed storage 2S globulin from narbon beans.

PMID- 9532804
TI  - Extracellular dextran-induced p-nitrophenyl-alpha-D-glucoside-hydrolyzing enzyme
      of Bacillus circulans KA-304: a producer of Schizophyllum commune-lytic enzyme.
AB  - p-NP-alpha-D-Glucoside-hydrolyzing activity in the culture filtrate of Bacillus
      circulans KA-304, a producer of Schizophyllum commune cell-wall lytic enzyme,
      increased remarkably when the bacterium was grown on dextran as a carbon source.
      It was suggested that the increase of the activity was caused by increases of two
      major species, alpha-D-glucosidase I and alpha-D-glucosidase II. alpha-D
      Glucosidase I, which showed a certain reactivity toward dextran, was isolated
      from the filtrate (MW 70 kDa, 35-fold, 10% recovery). The enzyme was stable
      around pH 6.5-7.5 and showed its highest activity at pH 6.5. The enzyme
      preparation inactivated with p-chloromerucuribenzoic acid recovered its activity
      by incubating with ditiothereitol. Its substrate specificity suggested that the
      enzyme was an exo-type enzyme with certain affinity toward alpha-1,6-glucosidic
      linkage.

PMID- 9532803
TI  - Multidrug resistance phenotype conferred by overexpressing bfr2+/pad1+/sks1+ or
      pap1+ genes and mediated by bfr1+ gene product, a structural and functional
      homologue of P-glycoprotein in Schizosaccharomyces pombe.
AB  - We investigated the mechanism of multidrug resistance conferred by overexpression
      of bfr2+/pad1+/sks1+ or pap1+ genes of Schizosaccharomyces pombe. Overexpression
      of bfr2+ did not confer multidrug resistance on a pap1-disrupted strain. In a
      mutant with bfr1+ (a putative membrane transporter which belongs to the ATP
      binding cassette superfamily) disrupted, overexpression of either bfr2+ or pap1+
      did not confer multidrug resistance. These findings suggest that bfr1+ acts as
      the most downstream effector of the multidrug resistance conferred by bfr2+ and
      pap1+ genes.

PMID- 9532805
TI  - Binding of the protein from Thermus aquaticus ISLtaq1 to its inverted repeat in
      vitro.
AB  - We have isolated from Thermus aquaticus an insertion-sequence-like genetic
      element (ISLtaq1) that induces thermotolerance and has a high sequence similarity
      to IS150 belonging to the IS3 family. An open reading frame on ISLtaq1, termed
      ORF1, encodes the ORF1 protein, which carries a DNA-binding motif. In this study,
      we found an imperfect inverted repeat in ISLtaq1. We next overproduced and
      purified a His-tagged ORF1 protein. Gel retardation analysis demonstrated that
      this protein specifically bound to an DNA fragment containing the inverted repeat
      in ISLtaq1. These results suggest that ISLtaq1 and the ORF1 protein are an
      insertion sequence and part of the transposase encoded by ISLtaq1, respectively.

PMID- 9532806
TI  - Overexpression of squalene-hopene cyclase by the pET vector in Escherichia coli
      and first identification of tryptophan and aspartic acid residues inside the QW
      motif as active sites.
AB  - An overexpression system for squalene-hopene cyclase (SHC) was constructed by
      using the pET3a vector, which is responsible for high expression with help from
      the strong T7 promoter when incorporated into E. coli BL21(DE3). Site-directed
      mutagenesis experiments prove that two amino acid residues of tryptophan and
      aspartic acid inside the QW-motif 5 resided as active sites.

PMID- 9532808
TI  - [Regional meetings of the Japanese Society of Otolaryngology. 1997. Abstracts].

PMID- 9532807
TI  - A new peptide-N4-(acetyl-beta-glucosaminyl)asparagine amidase from soybean
      (Glycine max) seeds: purification and substrate specificity.
AB  - We report here the isolation and characterization of a peptide-N4-(acetyl-beta
      glucosaminyl) asparagine amidase (peptide: N-glycanase) from soybean (Glycine
      max) seeds. The enzyme was purified to homogeneity with 6.5% yield from defatted
      soybean meal extract by ion-exchange chromatography, gel filtration,
      hydroxyapatite chromatography, and hydrophobic chromatography. The purified
      enzyme, designated PNGase-GM, had the apparent molecular mass of 93 kDa by SDS
      PAGE and 90 kDa by gel filtration, indicating this PNGase is a monomeric protein.
      The enzyme showed maximal activity at pH 4.5-5.0. PNGase-GM was capable of
      hydrolyzing the beta-aspartylglycosylamine linkage (GlcNAc beta 1-->Asn) of
      various glycopeptide substrates bearing high-mannose type, hybrid type, and
      xylose/fucose-containing plant complex type N-glycan units, while this amidase
      was far less active on the glycopeptides bearing sialylated animal complex-type
      glycans.

PMID- 9532809
TI  - [In search of new paradigms for the management of ischemic heart disease].

PMID- 9532810
TI  - [Effects of omega-3 acids on endothelium-dependent relaxation in
      hypercholesterolemic rabbits].
AB  - PURPOSE: To study the effect of omega-3 fatty acid on endothelium-dependent
      relaxation, total plasma cholesterol, LDL-cholesterol, HDL-cholesterol and
      triglycerides levels as well as, the malondialdehyde (MDA) content of the LDL
      particles and arterial wall. METHODS: Fourteen male rabbits were randomly
      assigned to hypercholesterolemic and omega-3 groups. The dose of omega-3 fatty
      acid utilized was 300g/kg/day during 15 days. All rabbits were fed a diet
      supplemented with cholesterol (0.5%) and coconut oil (2%) for four weeks. At the
      end of the experiment the animals were killed and the aorta removed for
      measurement of MDA content and the endothelium-dependent relaxation studies.
      Total plasma cholesterol, VLDL-cholesterol, LDL-cholesterol, HDL-cholesterol and
      triglycerides was measured by enzymatic kits. MDA was also measured in natives
      and oxidized LDL and arterial wall. RESULTS: Cholesterol and VLDL-cholesterol
      were increased significantly in the omega-3 treated animals. The triglyceride
      level was significantly reduced (p < 0.05). The MDA content was increased in the
      LDL particles and in the arterial wall (p < 0.05). Endothelium-dependent
      relaxation was significantly reduced (p < 0.05). CONCLUSION: Omega-3 fatty acid
      impairs the endothelium-dependent relaxation when administered to cholesterol fed
      rabbits, increases the cholesterol and reduces the triglycerides plasma levels.
      The lipid peroxidation of the LDL particles and arterial wall was increased.

PMID- 9532812
TI  - [Diagnostic value of exercise testing in the diagnosis of silent myocardial
      ischemia in elderly patients with systolic hypertension].
AB  - PURPOSE: To evaluate the diagnosis value of exercise testing for silent
      myocardial ischemia in systolic hypertension of the elderly. METHODS: We compared
      110 patients with systolic hypertension (group A) with 104 patients without
      hypertension (group B). They were submitted to an exercise test according to the
      Bruce protocol, between January/91 to December/94. Exercise was discontinued if
      target heart rate was achieved, or fatigue, dyspnea, severe arrhythmia,
      hypotension or significant ST segment depression > or = 2 mm/0.2 mV developed.
      RESULTS: Exercise testing showed ischemic ST depression in 22 (20%) of the
      elderly patients with hypertension systolic and 12 (11.5%) of control elderly
      patients. The exercise time was shorter in the hypertensives 7.1 +/- 2.9 min vs
      8.8 +/- 2.5 min. The ST depression was greater in the hypertensives than the
      control group: 2.5 +/- 0.8 min vs 1.9 +/- 0.4 min. Also the duration or ischemic
      ST depression was longer in the hypertensive patients than the control group 5.4
      +/- 2.8 min vs 3.4 +/- 1.9 min. CONCLUSION: Elderly hypertensive patients with
      systolic hypertension have more silent myocardial ischemia than elderly without
      hypertension. Among the elderly hypertensive patients there was a prevalence of
      silent ischemia that was 1.7 times higher than in the normotensive elderlies (20%
      vs 11.5% P < 0.003).

PMID- 9532811
TI  - [Complete atrioventricular septal defect. Anatomo-functional correlation between
      patients with and without Down's syndrome].
AB  - PURPOSE: To compare clinical course, causes and symptoms beginning enset time in
      children with complete atrioventricular canal with and without Down's syndrome.
      METHODS: Records of 80 patients < 2 years of age, were reviewed. There were 55
      (69%) with Down's syndrome-group I (GI) and 25 (31%) without-group II (GII). Age
      at synpton enset intensity, functional class, clinical repercussion and anatomic
      variations in patients undergoing corrective surgery were evaluated. RESULTS:
      Mean age at symptoms onset was similar for the two groups (50 +/- 75 days). Class
      II (NYHA) was more frequent in GI (31 patients-56.5%) and class III-IV (NYHA) in
      GII (19 patients-76%) p < 0.005. Clinical repercussion evaluation showed that
      congestive heart failure was present in 34 (62%) patients of GI and 21 (84%) of
      GII; and, pulmonary hypertension was in 21 (38%) patients of GI and 4 (16%)
      patients of GII p < 0.04. Mean pulmonary arterial pressure of 50 mmHg or more was
      present in 68% of children with Down's syndrome and in 35% of GII. Clinical
      course until surgical correction was down hill in 33 (60%) from GI and 21 (84%)
      from GII p < 0.03. Seventy seven patients underwent surgical correction. CAVC
      type A of the Rastelli classification was predominant in both groups, GI 37 (67%)
      GII 25 (100%). There or more severe valvar morphologic lesions in group II (38%)
      than in group I (8%). CONCLUSION: There seems to be a pulmonary vascular
      hyperreactivity predominance in Down's children and cardiac insufficiency signs
      in the normal genetic group.

PMID- 9532813
TI  - [Safety and feasibility of dobutamine-atropine stress echocardiography].
AB  - PURPOSE: To study the safety and feasibility of dobutamine-atropine stress
      echocardiography (DASE) in patients with known or suspected coronary artery
      disease. METHODS: There were 3,000 DASE that were studied in a prospective
      fashion. All symptoms and side effects were stored in a data base format.
      RESULTS: Major test-related complications observed included one case of
      myocardial infarction, four cases of sustained ventricular tachycardia and five
      cases of atropine intoxication. There was no death or ventricular fibrillation as
      a direct or indirect consequence of the test. The infusion protocol allowed to us
      to examine patients using beta blockers, and led to 95% feasibility. CONCLUSION:
      DASE is a safe and feasible method for the study of patients with suspected or
      known coronary artery disease.

PMID- 9532814
TI  - [Enalaprilat in the prevention of left ventricular hypertrophy induced by
      isoproterenol].
AB  - PURPOSE: To evaluate whether the enalaprilat, angiotensin I enzyme conversion
      inhibitor, could prevent the left ventricular hypertrophy (LVH) induced by
      isoproterenol. METHODS: Seventy two adult Wistar-EPM rats were divided into four
      groups: CON, control; ENA, treated with enalaprilat (1 mg/kg via subcutaneous
      (s.c.) for 8 days); ISO, treated with isoproterenol (0.3 mg via s.c. for 8 days)
      e ENA + ISO, treated with both drugs simultaneously. Each group had the arterial
      blood pressure, cardiac rate and the left ventricle (LV) weight determined in 10
      animals. In 8 animals from each group a small sample was taken from the LV and
      stained with hematoxyline-eosine and picrosirius for morphometric and ultra
      structural studies with optic and transmission electronic microscopy. RESULTS:
      The ISO group showed that the LV weight increased 47% in comparison with control.
      On the other hand the ENA + ISO group showed only 22.1% increase (p < or = 0.05).
      The morphometric and ultra-structural analyses revealed that isoproterenol
      induced cardiomyocite hypertrophy and augmented the content of the type I
      collagen in the cardiac interstitium. CONCLUSION: Enalaprilat inhibited the
      isoproterenol action on the cardiomyocite, avoiding partially the LVH and
      decreasing the content of collagen fibers.

PMID- 9532815
TI  - [Ambulatory blood pressure monitoring in normal adolescents].
AB  - PURPOSE: To evaluate technical aspects of ambulatory blood pressure monitoring
      (ABPM) in normal adolescents. METHODS: Forty five normal adolescents (27 female),
      10-18 years old. RESULTS: ABPM recordings showed a mean of 90% successful
      readings; 30% of the patients complained of sleep disruption related to the
      functioning of the ABPM monitor; the mean systolic, diastolic and heart rate fall
      during sleep was 13%, 23% and 24% respectively; the mean systolic and diastolic
      blood pressure load, while awake, was in male adolescents 25.4 +/- 27.7% and 11.8
      +/- 14.6%, and in female adolescents, 17.5 +/- 18.7% and 11.8 +/- 11.4%,
      respectively; the mean systolic and diastolic blood pressure load, while asleep,
      was in male adolescents 15.4 +/- 22.9% and 2.8 +/- 4.9% and, in female
      adolescents, 10.5 +/- 18.2% and 1.8 +/- 2.7%, respectively; the mean diastolic
      values of the first two hours of recording were higher than the ones obtained
      during the rest of the hours of recording while awake; different mean systolic,
      diastolic and heart rate values were found during the afternoon and nocturnal
      sleep periods. CONCLUSION: ABPM was well accepted by the adolescent population,
      with good technical results.

PMID- 9532816
TI  - [Stents for bifurcational coronary lesion].
AB  - We describe two cases of coronary angioplasty with stents implantation in
      bifurcational lesion of the left anterior descending artery and the diagonal
      branch using new techniques successfully performed. Angiographic reestenosis was
      not present after seven months in one case and the patient was asymptomatic after
      six months of clinical follow-up in the other.

PMID- 9532818
TI  - [Orthomolecular medicine based on evidence].

PMID- 9532817
TI  - [Emergency percutaneous balloon mitral valvuloplasty in a pregnant woman].
AB  - We report the case of a 33-year-old woman in the 28th week of pregnancy and with
      signs of fetal death, admitted to hospital in an emergency due to pulmonary edema
      secondary to severe mitral valve stenosis. Intensive medical treatment was
      unsuccessful and the patient was submitted to an emergency percutaneous balloon
      mitral valvoplasty with prompt clinical improvement. Subsequent clinical
      deterioration secondary to fetal death was managed by cesarean section resulting
      in clinical establization. The patient was discharged 10 days after admission and
      at 11 months after the procedure she had mild symptoms without drug therapy and
      echocardiographic signs of mild residual mitral stenosis (mitral valve area: 2.0
      cm2).

PMID- 9532819
TI  - [Anatomo-clinical correlation. Case 4/97 (Instituto do Coracao do Hospital das
      Clinicas-FMUSP)].

PMID- 9532820
TI  - [Rheumatic disease].

PMID- 9532822
TI  - [Tilt test for the evaluation of syncope of unknown origin].
AB  - The aim of this study was to evaluate the usefulness of head up tilt testing in
      patients with syncope of unknown origin. Between January 1994 and September 1995,
      93 patients were referred for tilt table assessment due to recurrent syncope of
      uncertain etiology. There were 42 men (mean age 59 years). Thirty healthy
      volunteers served as a control group. The specific protocol used involved an
      initial period of supine rest for 15'. Baseline blood pressure (BP) and heart
      rate (HR) were recorded. This was followed by a tilt to 80 degrees for 30', BP
      and HR were measured every minute during the procedure. The test was considered
      positive when symptoms appeared associated with one of the following responses:
      systolic BP decreased more than 30 mmHg (vasodepressor), bradicardia or asystolia
      for up to 3" (cardioinhibitory) or mixed. RESULTS: The tilt test was positive in
      31 of 93 patients (33%). Seventeen patients (55%) had a vasodepressor response, 3
      patients (9%) a cardioinhibitory response and 11 patients (36%) mixed responses.
      The clinical manifestations were 62% near syncope, 19% syncope and the other
      patients presented dypsnea or dizziness. The symptoms disappeared promptly after
      adopting the supine position. None of the 30 healthy volunteers developed
      symptoms. We conclude that head up tilt test is a safe and effective method for
      identifying a neurocardiogenic origin in a syncope of uncertain etiology.

PMID- 9532821
TI  - [Survival of patients with myasthenia gravis after thymectomy. Analysis of 100
      cases].
AB  - In order to evaluate the survival of patients with myasthenia gravis (MG) after
      thymectomy (T), 100 patients with MG in which T had been performed between 1967
      and 1995 were studied. Patients were divided into different groups for their
      analysis: patients with thymoma (TI), 22 cases; and patients without thymoma
      (NTI), 78 cases. In addition those patients belonging to the latter group were
      further separated according to the date of their surgery into two other
      subgroups: patients operated before 1980 (A80), 43 cases; and after 1980 (D80),
      35 cases; trying to evaluate the prognostic implications of the therapeutical
      advances achieved over the last 15 years. The population studied was composed
      mainly of women (78%) but with a slight predominance of men in TI. The mean age
      was 29.47 years (range 10-70) for the entire population, with a tendency toward
      older ages in TI (mean 46 years, range 23-70). The mean follow-up period was 4.3
      years (range 0.08-23.2) without significant differences between TI and NTI. The
      results showed that the overall mortality rate was 16/100 (16%) [Fig. 1], with
      nine of those deaths corresponding to TI (9/22, 40.91%) and only the remaining
      seven to NTI (7/78, 8.97%). These differences in mortality rate between TI and
      NTI were statistically significant in all the specific times of follow-up
      analyzed up to 10 years after surgery (p < 0.05) [Fig. 2]. Notoriously, all
      deaths in NTI occurred in the A80 subgroup giving a p value < 0.001 when compared
      with D80 [Fig. 3]. In terms of morbidity, 55/100 (55%) reached complete clinical
      remission (CCR) defined by the complete absence of symptoms related to MG: 8/22
      (36.36%) in TI and 47/78 (60.25%) in NTI [Fig. 4]. Most interestingly the
      differences were statistically significant (p < 0.01) when the rates of CCR in
      A80 and D80 were compared for all the times assessed [Fig. 5-6-7-8]. It can be
      concluded that the best results in survival in MG after T are obtained in
      patients without thymoma and also that the benefits of the rational use of modern
      therapeutic modalities, including surgery and immunosuppression with drugs, can
      offer those patients high possibilities of leading completely normal lives.

PMID- 9532823
TI  - [Identification of Epstein-Barr virus in nasopharyngeal carcinomas in Argentina.
      Its relation with p53 and the determination of proliferation indices].
AB  - Thirty-seven nasopharyngeal carcinomas were studied obtaining the tissue from
      nasopharyngeal biopsies that were formalin fixed and paraffin embedded. The
      patients were born in Argentina, 23 men and 14 women with a mean age of 50 years.
      Histologically the tumors were classified as queratinizing squamous cell
      carcinomas, 1 case (2%); non-queratinizing squamous cell carcinomas, 15 cases
      (41%) and undifferentiated carcinomas, 21 cases (57%). The proliferating index
      (PI) was determined using monoclonal antibodies against PCNA and Ki-67 (MIB-1),
      resulting in 26% for PCNA and 17% for Ki-67 while no differences were found
      comparing PI with histological type and cases with clinical stage III and IV. The
      PI was of 2% in the 3 cases with clinical stage II. Immunostains for p53 were
      positive in 30 out of the 37 cases with no differences between the histological
      types, exception made for the queratinizing carcinoma which was negative. With a
      cut off point of 7% in the 12 cases with follow up, two groups were found with a
      mean survival of 35 and 12 months, a finding that was not statistically
      significant. Epstein-Barr virus was detected by PCR using the paraffin embedded
      material in 31 out of the 37 cases: 21 were undifferentiated carcinomas and 15
      non-queratinizing squamous cell carcinomas; the queratinizing squamous cell
      carcinoma was negative. These results, published for the first time in samples
      from Argentinian patients are similar to those found in areas of high and low
      incidence of nasopharyngeal carcinomas and can be of clinical use in determining
      the nasopharyngeal origin of a cervical metastatic lymph node of an unknown
      primary.

PMID- 9532824
TI  - [Vitamin E as protective agent against hemolysis in leprosy patients under
      dapsone treatment].
AB  - Dapsone (4,4'diaminodiphenyl-sulphone) commonly used in the treatment of patients
      who suffer from leprosy, is a strongly oxidative drug, producing damage to the
      red cell membrane. This study investigated whether Vitamin E would have a
      protective effect on the red cell membrane from oxidant damage caused by Dapsone
      in patients with leprosy. We have studied 16 patients for 4 months, divided into
      two groups. Group 1 (n = 7) dapsone (DDS): 100 mg/day; Group 2 (n = 9) dapsone:
      100 mg/day in addition with Vitamin E: 800 U/day. We did not include patients
      with low levels of Glucose-6-Phosphate Dehydrogenase (G-6-PD) because of their
      sensibility to this drug. At the beginning of the treatment we determined the
      level of G-6-PD. All patients showed a normocytic normochromic anemia with a
      decrease in Haptoglobine levels (below 5 mg/dl). Statistical analyses showed that
      reticulocyte counts did not present significant differences between groups all
      through evolution. As for methemoglobin (Hi) we observed in Group 1 an increase
      between the first and the fourth month, which was not seen in group 2.
      Statistical analyses of the results suggest that oral Vitamin E confers partial
      protective effect and does not correct the hemolysis parameters produced by
      Dapsone treatment except for Hi levels which were more sensitive to the oxidant
      damage.

PMID- 9532825
TI  - [Prophylaxis of prenatal toxoplasmosis].
AB  - Prenatal toxoplasmosis infection occurs when a previously seronegative women
      acquires the infection during her pregnancy. In order to detect early infected
      women and give them the correct treatment, systematic serological screening must
      be applied. A total of 3049 pregnant women were retrospectively studied and
      controlled in our service from 05/92 to 03/94 in order to a) detect
      seroprevalence y b) prove the efficiency of our controls. Indirect
      immunofluorescence was used to measure specific antibodies and ELISA for specific
      IgM. The total seroprevalence was 58.9%; 41.1% of the women were seronegative and
      susceptible to acquire the primary infection. The prevalence in the different
      groups according to age, was: < 19 years old: 58.8%; 20-29 years old: 56.9%; 30
      39 years old: 64.2%. Only 8.5% of the whole population showed high titles in
      their first control and, 55% of them were checked correctly. Two primoinfections
      were found. Only 5% of the seronegative women received a second control during
      pregnancy. It can be concluded that: a) the high-risk group is large so that it
      is necessary to apply a suitable and systematic serological control; b) IgM
      antibody detection resulted very useful in order to avoid taking the second
      sample; c) the follow up of the negative cases was poor, therefore it was
      impossible to get an adequate registration of primary contacts.

PMID- 9532826
TI  - [Chagas disease. Serologic response to crude and semipurified T. cruzi antigens
      in different clinical groups of patients].
AB  - The immune response of people infected by the protozoan parasite Trypanosoma
      cruzi varies in indeterminate or chronic periods of infection, according to the
      course of the disease. Apparently, the antibody pattern is different in
      asymptomatic patients than in patients with cardio-myopathy. The study of those
      differences for clinical purposes depends on the availability of adequate
      antigenic preparations. We studied the behavior of crude and partially purified
      antigens of T. cruzi in acute and chronically infected patients. The level of
      total antibodies was measured by conventional serology (indirect
      immunofluorescence, IF, and indirect hemagglutination, HA) and the level of
      antibodies against different fractions of antigens obtained by analytical chroma
      tofocusing, by using enzymatic immunoassay (ELISA). Chronic patients were
      classified according to Kuschnir et al. in: Group 0 (G0) or Group 1 (G1)
      according to the absence or presence of electrocardiographic alterations. In
      acute patients, conventional serology was negative in most cases. However, the
      ELISA performed with the soluble fraction of the lysate of parasites, showed
      positive results in 60% of patients. By classical serology, the behavior of
      chronic patients sera was different in the two groups when assayed by IF; G1
      showing more elevated titles than G0. On the other hand, by HA the results were
      similar in both groups. When the sera were studied by ELISA using the different
      fractions, the fraction collected at pH 4-4.5, named F IV, detected distinct
      reactivity in some of, but not in all, the patients of G1. In that subgroup, the
      highest ELISA indes (optical density of sera vs OD of negative controls) was
      observed. By associating IF plus FIV-ELISA the results became more apparent: 22%
      of sera showed titles by IF equal or more than 1:128 and ELISA index equal or
      more than 3.5, whereas only 2% of G0 showed this characteristic and all the sera
      with index equal or more than 4 belonged to G1. With lesser antibody titles it
      was not possible to differentiate between the two groups. It can be concluded
      that the study of the pattern of antibodies by using different antigens and
      serological methodologies can offer useful information in the different periods
      of Chagas disease, by adding the higher sensitivity of methods using crude
      antigens with the more specific and discriminative results obtained by the use of
      purified or synthetic antigens.

PMID- 9532827
TI  - Natural estrous cycle in normal and diabetic bitches in relation to glucose and
      insulin tests.
AB  - The influence of spontaneous "sex seasons" on blood sugar (BS) and serum insulin
      levels was studied in bitches with natural diabetes mellitus (DM) and normal
      controls, in the basal condition and during glucose and insulin tests, was
      studied. DM increased basal BS, reduced glucose tolerance, distribution space
      (DS) and clearance from blood, and induced resistance to insulin hypoglycemic
      action. In normals occurrence of "seasons", inconsistently modified basal BS,
      increased glucose tolerance and DS; during estrogenic phase (EP), these variables
      were above those during luteal phase (LP). In diabetics at LP, BS found in
      lasting condition and during glucose test were higher than in diabetic bitches at
      EP (respective values at anestrous (A) in between) and glucose DS was smaller.
      Rate of glucose clearance from blood remained unaffected by "seasons" in both dog
      groups. Basal serum IRI was not modified by DM or "seasons". In normals, serum
      IRI response to glucose load was nonsignificant during A and increased during the
      "seasons"; either insulin DS or the rate of insulin clearance from blood stream
      remained unchanged under the circumstances, the increase being mediated by
      insulin secretion. During EP, the increase was particularly intense and mean
      insulinogenic index (MII) rose. During LP, MII returned to A value, whereby
      diabetic states might be manifest. Serum IRI profiles during insulin test were
      not modified by "seasons" in normal bitches; such response in diabetic bitches
      was intense during A, then decreased (EP) or was later abolished (LP). Either in
      normal or diabetic bitches, the sensitivity to exogenous insulin hypoglycemic
      action remained unchanged in spite of "seasons". In diabetic bitches at A, serum
      IRI after glucose challenge peaked higher than in respective normal controls
      (insulin clearance and insulin DS were similar): they exhibited relative insulin
      shortage and resistance to insulin hypoglycemic action partly compensated by
      promoted insulin secretion. Along with "season", abolished serum IRI response to
      glucose load in diabetics was observed. During EP, extrapancreatic factors
      regulating serum IRI concentration and MII did not change in respect to A,
      whereby abolishment appears mediated by depressed insulin secretion. During LP,
      insulin antagonism in conjunction with 1) absolute insulin deficiency and 2)
      intense decrease in MII appears as a powerful factor exposing diabetic bitches to
      a severe or fatal derangement in diabetic disease.

PMID- 9532828
TI  - [Left ventricular structure and function in young male students of La Plata
      University with stage I hypertension].
AB  - From an homogeneous population of 219 male medical students of La Plata
      University (20.9 +/- 1.6 years) who underwent a blood pressure screening, 34 were
      selected for measurements of left ventricular structure and function. Considering
      the JNC-V classification, samples from two groups were selected for comparisons:
      Optimal blood pressure (OBP) (21 males, 20.33 +/- 1.8 years) and Hypertensives
      stage I (H) (13 males, 20.85 +/- .66 years). The H showed values of body mass
      index (BMI) and heart rate (HR) higher than OBP (BMI OBP: 22.5 +/- 0.38 kg/m2, H:
      24.26 +/- 0.84 kg/m2 -p < 0.04; HR OBP: 69.9 +/- 1.53 lat/min-H 80.5 +/- 3.58
      lat/min -p < 0.03). Although the H were not reaching values of left ventricular
      mass index (LVMI) or septal (S) and posterior wall thickness to be considered
      hypertrophics, they were exceeding the OBP group (LVMI OBP: 89.6 +/- 3.33 g/m2,
      H: 124.5 +/- 6 g/m2 -p < 0.01; S OBP: 8.7 +/- 0.17 mm, H: 11.5 +/- 0.04 mm; P
      OBP: 7.9 +/- 0.18 mm, H: 10 +/- 0.13 mm -p < 0.01). Cardiac index (CI) was
      increased in H (OBP: 3.3 +/- 0.14 l/min/m2, H: 4.8 +/- 0.36 l/min/m2 -p < 0.01)
      supporting the existence of a hyperkinetic circulatory phase. OBP showed total
      peripheral resistance (TPR) higher than H group (OBP: 17 +/- 0.8 mmHg/l.min.m2,
      H: 13 +/- 1 mmHg/l.min.m2 -p < 0.008). Left ventricular (LV) systolic function
      indexes were not different in the two groups analyzed. The pattern of left
      ventricular late filling was however different between the two groups. The area
      of late diastolic flow (Area A) was lower in OBP (OBP: 2.64 +/- 0.09 cm2, H: 3.78
      +/- 0.95 cm2 -p < 0.01) independently of HR value (adjusted mean OBP: 2.9 +/-
      0.09 cm2, H: 3.52 +/- 0.95 cm2 -p < 0.01). The early filling fraction (EFF) was
      also detecting a significant shift to more prominent late diastolic filling in H
      (OBP 0.72 +/- 0.06%, H: 0.64 +/- 0.01% -p < 0.01) independently of HR values
      (adjusted mean PAO: 0.71 +/- 0.96%, H: 0.65 +/- 0.01% -p < 0.01). Healthy young
      males with hypertension stage I have similar LV systolic function, increased CI,
      LVMI, LV wall thickness, decreased TPR and evidence of impaired LV filling with
      shift of the pattern of filling to a late flow.

PMID- 9532829
TI  - [Etiology of acute lower respiratory tract infections among children younger than
      5 years old in Santa Fe].
AB  - The etiology of acute lower respiratory tract infections (ARI) and nasopharyngeal
      bacterial carriage in children less than 5 years old living in Santa Fe city,
      Argentina, was studied. A total of 518 children were included in the study: 450
      suffering from ARI and 68 asymptomatic children. Blood samples, pleural effusions
      and nasopharyngeal secretions (NS) were obtained from children for bacterial
      isolations. NS was also used for fluorescent antibody techniques, and serum
      samples were employed for detecting IgM anti Chlamydia trachomatis. A bacterial
      pathogen was isolated from blood in 6.2% (14/224) of the children with ARI. A
      total of 11 Streptococcus pneumoniae (five of them oxacillin resistant), two
      Haemophilus influenzae and one Staphylococcus aureus strains were isolated. The
      most frequently detected pathogen in the ARI group was respiratory syncytial
      virus (RSV). It was found in 23.3% (105/450) of the children with ARI. Among
      children with risk of Chlamydia trachomatis infection, 24% presented high titters
      of specific IgM antibodies. Main bacteria carried in NS in the ARI group were
      H.influenzae (31.6%) and S. pneumoniae (23.4%) while viridans streptococci
      (26.5%), H.influenzae (23.5%) and Moraxella catarrhalis (22.1%) were more
      frequently isolated from controls. The most common pneumococcal types were 14 and
      7 and the main type of H.influenzae was b biotype I. During the period of this
      study, the susceptibility of the pneumococcal isolates to oxacillin decreased
      from 60% to 50.8%, and the H.influenzae susceptibility to ampicillin fell from
      92.3% to 79%. All the H.influenzae type b isolations were susceptible to
      ampicillin.

PMID- 9532830
TI  - [Renal vascular lesion and microangiopathic hemolytic anemia in systemic lupus
      erythematosus].
AB  - A 22 year-old woman with a seven year history of (SLE) was readmitted because of
      oliguria, edema, dyspnea and arterial hypertension. She had a previous biopsy
      diagnosis of focal glomerulonephritis, (WHO III b), and had been treated with
      immunosuppressors and steroids. Laboratory data showed lupus activity, AHM with
      thrombocytopenia, nephrotic-range proteinuria and renal failure. A second renal
      biopsy was performed showing diffuse proliferative nephritis, (WHO IV), in
      association with noninflammatory necrotizing vasculopathy with luminal
      obliteration. She started with hemodialysis and was subsequently treated with
      methylprednisolone pulses, plasmapheresis, cyclophosphamide and oral steroids.
      During the inpatient period, she had generalized seizures, acute lung injury and
      pulmonary hemorrhage. These complications, the AHM and the thrombocytopenia
      receded totally. Renal function was never resumed. We emphasize that this
      association of diffuse proliferative nephritis with noninflammatory necrotizing
      vasculopathy is not infrequent and has a poor renal prognosis. The AHM with
      thrombocytopenia was interpreted as secondary to endothelial cell damage due to
      vasculopathy.

PMID- 9532831
TI  - [Sarcomatoid carcinoma of the lung].
AB  - Sarcomatoid carcinomas of the lung are very uncommon tumors and their biological
      behavior remains controversial. Here we describe a case of a 62 year old male
      with an endobronchial mass and subjected thereafter to right upper and middle
      bilobectomy. A squamous carcinoma with a sarcomatous component resembling a
      fibrosarcoma was found at microscopic examination. Although there is neither
      agreement on the denomination nor on the histogenesis of these tumours, it is
      recognized that they are highly aggressive. Therefore, in order to provide the
      best possible treatment it appears recommendable to supply a detailed description
      of the different components of the tumor at the time of the histopathological
      diagnosis.

PMID- 9532832
TI  - [Endometrial carcinoma with polycystic ovaries. Report of two cases in women
      younger than 40 years old].
AB  - Endometrial carcinoma is rare in women under 40 years of age. The incidence in
      this age group has been variously reported to be from 1% to 8% of all cases of
      endometrial carcinoma. Women at high risk, as a result of excess estrogenic
      stimulation are those with polycystic ovaries, long-standing estrogen users and
      functioning granulosa cell tumors and thecomas. We report two cases of young
      women with endometrial carcinoma and polycystic ovaries (Stein-Leventhal
      syndrome).

PMID- 9532833
TI  - [Collagen nephritis].
AB  - Fibrillar collagen in the glomeruli is considered specific of the nail-patella
      syndrome. A new nephropathy with diffuse intraglomerular deposition of type III
      collagen without nail and skeletal abnormalities has been described. We report
      the case of a 26-year-old woman who presented persistent proteinuria, hematuria,
      deafness without nail and skeletal abnormalities. The renal biopsy showed focal
      and segmental glomerulosclerosis by light microscopy. The electron microscopy
      revealed the presence of massive fibrillar collagen within the mesangial matriz
      and the basement membrane. This is the first patient reported in our country. We
      emphasize the usefulness of electron microscopy in the study of glomerular
      diseases.

PMID- 9532834
TI  - [Mental retardation, hypothermia, mitral stenosis and sepsis].

PMID- 9532835
TI  - [Inflammatory response to acute Trypanosoma cruzi infection].
AB  - The acute stage of Trypanosoma cruzi infections related to high parasitemia is
      characterized by the presence of inflammatory infiltrates in several tissues,
      including the heart and squeletal muscle, as well as by an increased production
      of inflammatory mediators, such as gamma-interferon (IFN-gamma), tumor necrosis
      factor (TNF), interleukin-1 (IL-1) and oxygen and nitrogen reactive
      intermediates. The activation of phagocytic cells seems to be closely related to
      both the inflammatory process and host resistance to the infection. Herein, the
      inflammatory mediators produced in vivo and their relationship with the tissue
      damage and TH1 immune response are reviewed.

PMID- 9532836
TI  - [Coevolutive mechanisms between retroviruses and their hosts. The murine mammary
      tumor model].
AB  - Mouse mammary tumor virus (MMTV) is a type B retrovirus that is transmitted as an
      infectious milk-borne particle and that causes mammary carcinomas by insertional
      activation of cellular protooncogenes. Germ line infections result in endogenous
      Mtv proviruses integrated in the genome of most mouse strains. These endogenous
      proviruses have been integrated into the genomes of mice for only the past 3-5
      million years. The open reading frame present in the 3' long terminal repeat
      (LTR) of the provirus encodes a superantigen (SAg) which is able to stimulate a
      large proportion of T cells sharing a common T-cell receptor beta chain variable
      domain (v beta). Expression of this SAg is critical to the MMTV life cycle. After
      expression of the SAg in B cells a significant number of T cells are recruited to
      respond to these MMTV infected cells. As a consequence both the T cells
      expressing the relevant TCR V beta domain and the infected B cells become
      activated and start dividing. This would facilitate integration of MMTV and
      amplify the number of virus infected lymphocytes. Most likely during lactation
      the mammary glands become receptive to viral infection. The presence of
      endogenous Mtvs induces an early clonal deletion of reactive T cells. For this
      reason it has been argued that the presence of these proviruses confers a
      selective advantage to the mouse population by protecting the host from infection
      with an exogenous MMTV coding for a cross-reactive SAg. However, recent results
      discussed herein suggest that Mtv proviruses may also be detrimental to the mouse
      population by participating in recombinations with exogenous MMTVs, giving rise
      to highly tumorigenic recombinant particles. These results are discussed in the
      light of recent reports suggesting the involvement of viral sequences with a high
      homology to MMTV in human mammary tumorigenesis.

PMID- 9532837
TI  - [Glucocorticoid resistance syndrome].

PMID- 9532838
TI  - [Resistant hypertension. A difficult but solvable problem].

PMID- 9532839
TI  - [A century and a half of the first surgical anesthesia].

PMID- 9532840
TI  - Improving the general practitioner for better health.

PMID- 9532841
TI  - Systemic vasculitis: a difficult diagnosis.

PMID- 9532842
TI  - What is primary care anyway?

PMID- 9532843
TI  - Optimal search strategy for clinical trials in the Latin American and Caribbean
      Health Science Literature Database (LILACS).
AB  - OBJECTIVE: To define and disseminate the optimal search strategy for clinical
      trials in the Latin American and Caribbean Health Science Literature (LILACS).
      This strategy was elaborated based on the optimal search strategy for MEDLINE
      recommended by Cochrane Collaboration for the identification of clinical trials
      in electronic databases. DESIGN: Technical information. SETTING: Clinical Trials
      and Meta-Analysis Unit, Federal University of Sao Paulo, in conjunction with the
      Brazilian Cochrane Center, Sao Paulo, Brazil. (http://www.epm.br/cochrane). DATA:
      LILACS/CD-ROM (Latin American and Caribbean Health Science Information Database),
      27th edition, January 1997, edited by BIREME (Latin American and Caribbean Health
      Science Information Center). LILACS Indexes 670 journals in the region, with
      abstracts in English, Portuguese or Spanish; only 41 overlap in the MEDLINE
      EMBASE. Of the 168,902 citations since 1982, 104,016 are in human trials, and
      38,261 citations are potentiality clinical trials. Search strategy was elaborated
      combining headings with text word in three languages, adapting the interface of
      the LILACS. We will be working by locating clinical trials in LILACS for Cochrane
      Controlled Trials Database. This effort is being coordinated by the Brazilian
      Cochrane Center.

PMID- 9532845
TI  - Effect of high-dose fentanyl on renal function in dogs.
AB  - Our objective was to determine the effects of high-dose fentanyl on canine renal
      function (RF). We anesthetized with sodium pentobarbital (SP) 16 dogs, randomly
      divided into 2 groups: in G1, SP was given alone, and in G2, combined with 0.05
      mg.kg-1 fentanyl. All animals were ventilated artificially and had catheterized
      left and right femoral veins and left femoral artery for fluid infusion, drug
      administration, blood collection, and hemodynamic measurement. Urine was
      collected throughout the experiment. Attributes of RF were studied. SP did not
      alter RF, which was significantly altered by fentanyl. In G2, slower heart rates,
      mean arterial pressure, creatinine clearance, urinary output, osmolar clearance
      and fractional excretion of sodium and potassium were observed. G1 had a behavior
      attributed to extracellular volume expansion and no RF alterations. In G2, we
      observed significant decreases in RF due to opioid-induced hemodynamic changes,
      not discarding the possible action of aldosterone.

PMID- 9532844
TI  - Use of biofeedback (BFB) in the treatment of fecal incontinence after surgical
      correction of anorectal malformations by posterior sagittal anorectoplasty
      (PSARP).
AB  - OBJECTIVE: To evaluate biofeedback (BFB) responses to rehabilitation techniques
      and physical exercises in incontinent or partially continent anorectal
      malformations patients after posterior sagital anorectoplasty (PSARP). DESIGN:
      Prospective study. SETTING: Pediatric Surgery-Department of Surgery-UNIFESP-EPM.
      PATIENTS: The authors report on 14 patients with anorectal malformations (4 with
      partial fecal incontinence after primary PSARP; 6 with fecal incontinence after
      primary PSARP; 3 with partial fecal incontinence after secondary PSARP; and 1
      with fecal incontinence after secondary PSARP). All patients were rehabilitated
      via a BFB program of exercises in order to improve the function of the anal
      sphincteric muscular complex for a period of 1-3 years. MAIN OUTCOME MEASURE:
      Clinical and manometric control. RESULTS: After BFB, of 4 partially continent
      patients after primary PSARP, 3 became continent; of 6 incontinent patients after
      primary PSARP, 4 became continent; of 3 partially continent patients after
      secondary PSARP, 1 became continent, 1 showed no improvement and 1 became
      incontinent (infection + abscess + fibrosis + important anorectal stenosis). The
      incontinent patient after secondary PSARP showed no improvement. CONCLUSION: The
      authors concluded that BFB, used at the appropriate time with patient
      collaboration, is an important complement to the anatomical reconstruction of
      anorectal malformations in order to achieve good development and contractile
      functioning of the sphincteric muscular complex.

PMID- 9532846
TI  - Chondrosarcoma secondary to hereditary multiple exostosis treated by extended
      internal hemipelvectomy.
AB  - The authors report on the case of a 28-year-old patient with extensive
      chondrosarcoma of the left ischium and pubis involving hip joint, skin, and soft
      tissue of the gluteal region, secondary to hereditary multiple exostosis
      submitted to an extended internal Enneking type II and III hemipelvectomy. No
      prosthesis or arthrodesis was used. A few years ago, patients with extensive
      tumors like this one were treated with interilioabdominal amputation, resulting
      in a loss of quality of life. Two years after the limb-preserving surgery, this
      patient was disease free, with good functional results, including bipedal
      ambulation with support.

PMID- 9532847
TI  - Postnephrectomy arteriovenous fistula.
AB  - The development of the postnephrectomy arteriovenous fistula (PNAVF) between the
      renal vessels stumps is rare. Here we present a case report of PNAVF, and review
      the diagnosis, treatment and prevention. The most common clinical features
      include a loud murmur over the previous nephrectomy scar, and heart failure
      resistant to common medical treatment. A 58-year-old white woman was admitted to
      the hospital for a complete evaluation of an unexplained congestive heart failure
      with no response to common medical treatment. She had had a right nephrectomy for
      pyonephrosis 13 years before. The diagnosis of PNAVF was suspected because over
      the right lumbar region a definite trill was palpated, and on auscultation a
      harsh, machinery-like murmur was heard. The diagnosis was confirmed by aortogram
      and selective renal arteriography. In May 1989, the right arteriovenous was
      excised through a right subcostal transperitoneal approach. The renal vessel
      stumps were individually ligated and sutured separately close to aorta and vena
      cava. The patient's postoperative course was entirely uneventful in the following
      seven years. We conclude that during nephrectomy, the renal vessels should be
      ligated separately, and the transfixation in mass of the stumps avoided to
      prevent arteriovenous fistula.

PMID- 9532848
TI  - Platelet aggregation and lipoprotein levels in a patient with familial
      hypercholesterolemia after selective LDL-apheresis.
AB  - Platelet aggregation was studied in a patient with familial hypercholesterolemia
      immediately after apheresis selective for low-density lipoprotein (LDL), a lipid
      lowering procedure. This treatment reduced plasmatic levels of total and LDL
      cholesterol, apo B, and triglyceride. Increased platelet aggregation was reduced
      immediately after the apheresis in whole blood as well as in platelet-rich
      plasma. However, aggregation in washed platelets remained unchanged after LDL
      apheresis. In conclusion, in this patient reduction of LDL-cholesterol improved
      platelet function in the very short term.

PMID- 9532849
TI  - Adverse effects of vancomycin in children: a review of 22 cases.
AB  - Vancomycin has been frequently recommended for the treatment of multi-resistant
      infections. Twenty-two children undergoing vancomycin treatment were observed.
      Nine adverse effects were registered in 6 children: eosinophilia in 5 cases, skin
      rash in 2 cases, and an increase in plasma creatinine in 2 cases. All adverse
      effects remitted with withdrawal of the drug.

PMID- 9532850
TI  - Anatomical study of the renal veins observed during 342 living-donor
      nephrectomies.
AB  - The anatomical variations of renal veins observed during 342 nephrectomies in
      living donors are described, 311 cases on the left side and 31 on the right. The
      following anatomy of the renocava veins was observed: 1. On the left side the
      renal vein was always unique (311/311) and had two tributaries (suprarenal and
      gonadal veins) in 100 per cent and one or more renolumbar veins in 65.27 per
      cent, encircling the aorta in 1.07 per cent, was retroaortic in 1.4 per cent; and
      the inferior vena cava was double in 0.64 per cent; B- on the right side the
      renal vein was double in 29 per cent (9/31) and had only one tributary (gonadal
      vein) in one case, for 3.22 per cent (1/31); three or more renal veins in 9.7 per
      cent (3/31). We concluded that the left renal vein is always unique, presenting
      variations principally in its tributaries and trajectory. On the right side, the
      renal vein was double or triple in 38.79 per cent.

PMID- 9532851
TI  - Osseointegration & stress shielding.
AB  - Forty-two patients with a flexible distal non-cemented grit-blast hip stem have
      been examined to see if distal osseointegration (OI) had occurred. The minimum
      follow-up was 5 years. The definition of distal osseointegration was "the
      exhibition of distal bone hypertrophy with proximal bone atrophy with no
      radiolucency in a clinically stable situation". Osseointegration was noted in
      28.6%. It was seen more commonly in older females with greater canal fill,
      especially in the lateral x-ray. A control group in which the distal end of the
      stem was polished showed virtually no osseointegration. It appears therefore that
      with the simple expedient of polishing the distal stem, osseointegration in this
      zone can virtually be abolished.

PMID- 9532852
TI  - A simple assessment of bone quality prior to hip arthroplasty: cortical index
      revisited.
AB  - OBJECTIVE: To determine from routine clinical radiographs the diversity of
      cortical bone structural quality, i.e. the cortical index, of the proximal femur
      in 117 hips prior to hip arthroplasty and to evaluate its variance associated
      with patient demographic variables (gender, age at the time of surgery, height,
      weight, body mass index (BMI), and preoperative diagnosis). DESIGN: A cross
      sectional study was conducted using preoperative anteroposterior radiographs of
      the hip from 110 consecutive patients with 117 hip arthroplasty procedures, in
      which the patients at the time of surgery had an average age of 69.9 years
      (range, 19 to 92 years). The primary diagnosis leading to hip surgery was either
      degenerative joint disease (68 hips) or femoral neck fracture (49 hips). The
      cortical index, as a measure of cortical bone structural quality, was determined
      by one experienced reader for the proximal femur of each hip from conventional
      preoperative anteroposterior radiographs. Correlation analysis was performed
      between the cortical index and patient demographic variables to assess factors
      associated with the cortical index. RESULTS: For the entire cohort the average
      femoral cortical index was 47.9% (range, 25.8% to 64.8%). The hips in female
      patients had a lower average cortical index than in male patients (mean value of
      46.9% and 50.0% respectively). Statistical analysis demonstrated highest
      significant positive correlation between cortical index and BMI (r = +.441, p <
      0.0001) and with body weight (r = +0.396, p < 0.0001). Significant negative
      correlation was also found between cortical index and age at the time of hip
      surgery (r = -0.423, p < 0.0001). Significant differences were found between the
      cortical index and preoperative diagnosis with lower values among the hips
      diagnosed with femoral neck fractures (mean value, 43.9%) compared to hips with
      degenerative joint disease (mean value, 50.9%). CONCLUSION: A simple
      radiogrammetric parameter obtained from routine radiographs, i.e. the femoral
      cortical index, was found to demonstrate diversity of cortical bone structural
      quality among patients prior to hip arthroplasty. The cortical index decreased
      with older patients and increased with heavier (weight) and obese (BMI) patients.
      It was significantly lower among the hips with femoral neck fractures in patients
      who were predominantly fragile older females with lower body mass index, which
      would corroborate published studies associating lower bone mass with risk of hip
      fracture.

PMID- 9532853
TI  - HA versus grit blast tibial components in total knee replacement.
AB  - A comparison of 127 HA coated with 70 grit blast titanium noncemented tibial
      components in TKRs has been carried out. Clinically the results were
      indistinguishable. Radiolucency was significantly less in the HA coated
      components suggesting improved fixation. At 5 years, loosening and wear have yet
      to be seen. These results suggest that HA may be a useful adjunct to noncemented
      component fixation in total knee replacement.

PMID- 9532854
TI  - Application of ODH-titanium in total knee arthroplasty.

PMID- 9532855
TI  - Experience with proximal ingrowth implantation in hip revision surgery.
AB  - A 2 to 8 year review of 104 cases of Type III hip revisions with a proximally
      modular proximal ingrowth non-cemented stem has been carried out. Four re
      revisions were required, 1 early for a femur which was too broken up to support
      an implant, 1 for late sepsis re-activation, 1 for knee pain, and 1 at 4 years
      for aseptic loosening. Of the remainder, 81.8% had a good or excellent result
      with most problems being experienced in the acetabular side. 68.8% show no
      radiolucency and only 3 cases, including the revised one, show complete stem
      radiolucency. It is concluded that in the medium term, proximal ingrowth implants
      can be used in revision hip surgery.

PMID- 9532856
TI  - Eight years results of HA-coated primary total hip replacement.

PMID- 9532857
TI  - Revision total hip arthroplasty using hydroxylapatite-coated implants.

PMID- 9532858
TI  - Acetabular osteolysis with cementless cups: a 5 to 7 year follow-up.
AB  - We reviewed the results of 172 plasma-sprayed, titanium primary total hip
      arthroplasties inserted without cement and followed 5 to 7 years. Hips were
      replaced for a wide range of diagnoses and patient ages. No femoral components
      had been revised nor were considered unstable. Clinical results have been
      excellent; 88% of hips had either no or a slight amount of pain and only 5% of
      patients had thigh pain when specifically asked. Radiographically, this femoral
      component achieved stability after an initial subsidence in 9% of cases.
      Extensive femoral bone resorption was rare, and distal cortical hypertrophy was
      commonly seen. Pelvic osteolysis occurred in 16 (9%) cases and was considered
      major in 10 of these. It was the cause of failure of 3 acetabular components.
      Femoral endosteal lysis was not observed. We concluded that mechanical stability
      of the Mallory-Head titanium total hip prostheses is excellent. However,
      significant pelvic osteolysis has occurred commonly with this implant design, and
      will continue to pose major reconstructive problems in the future.

PMID- 9532859
TI  - HA coating. Ten-year experience with the CORAIL system in primary THA. The Artro
      Group.

PMID- 9532860
TI  - Experiences with metal on metal components in THR.
AB  - It can be stated that polyethylene wear can be shown as a problem in long term
      joint replacement. Metal-on-metal bearings are solving this problem as long term
      clinical and experimental investigations can demonstrate. To avoid the problem of
      high friction that was found to be a problem in older series, a new technique
      called Metasul with smaller diameter was invented. Intermediate results of Weber
      and our own data are showing promising results giving us the hope to solve the
      wear induced problem in hip replacement.

PMID- 9532861
TI  - Double coating TI-HAP: 5 years results with the total hip prosthesis alliance.

PMID- 9532862
TI  - The HA-coated ABG socket in revision arthroplasty.
AB  - The favourable results we achieved in primary THR with the ABG HA-coated
      hemispheric metal backed cup led us to use this same cup in revision
      arthroplasty. Changes in inclination and migration of the cup were measured, as
      well as the radiologic appearance of the bone-cup interface. The most important
      features are quick osseointegration and immediate stability. The early and three
      to five years results with the use of the ABG HA-coated cup in revision
      arthroplasty are promising.

PMID- 9532863
TI  - Bone cement--porous coated or hydroxylapatite coated prosthesis in total knee
      arthroplasty--state of the art--future trends.
AB  - 1. Cementation in total knees is here to stay. 2. Future improvements will lie in
      the area of implant interfaces--in the near term by improving our polyethylene.
      3. Cementless knees, with or without HA, may be indicated in the young, more
      active patient and where economic concerns have no impact on prosthetic
      selection.

PMID- 9532864
TI  - [Cochlear implants].
AB  - Cochlear implants aim at the rehabilitation of profound bilateral deafness. The
      cochlear implant is a prosthesis made out of surgically implanted cochlear
      electrodes connected to an external vocal processor. The external acoustic
      signals are converted into electrical signals coded by the vocal processor. They
      are then sent out, by a transcutaneous mode, to an internal receptor. This
      receptor transmits the information to the intracochlear electrodes. Initially,
      the cochlear implantation was recommended to patients totally deaf following a
      trauma, a degenerative disease of the inner ear, a meningitis or the use of
      ototoxic drugs. These patients could not gain from conventional hearing aids and
      were condemned to silence. More recently, the authors have been impressed by
      spectacular results with patients having lost their hearing during adulthood
      (postlingual). The challenge here is quite different, as its aim is to open up-
      and not to reopen--a child to a sensation that he has never perceived before.
      This allows the child to develop a coding, a recognition of the acoustic message.
      The first results are very encouraging. Scientifically, the implantation is also
      a research tool in various fields: surgical, neurophysiological,
      neuropsychological, speech therapy, social and cultural. The cochlear implant is
      an "avant-garde" project. It has changed our approach to profound deafness. It
      represents the only hope for the profoundly deaf person to reach a satisfactory
      rehabilitation and social integration.

PMID- 9532865
TI  - [Stromal proteases in the progression of breast cancer].
AB  - Matrix metalloproteases represent a family of proteases secreted as latent
      inactive enzymes able to degrade the majority of extracellular matrix components.
      These enzymes are overexpressed during several pathological tissue remodelings
      including tumor progression and tumor invasion. It was indeed classically
      admitted that matrix metalloproteases involved in tumoral progression were
      preferentially expressed by cancerous cells. Our studies on gelatinase A and
      stromelysin-3 have, however, demonstrated that their messenger RNAS are detected
      in fibroblasts of the peritumoral stroma in human mammary carcinoma and not in
      the cancerous cells themselves. By immunohistochemistry, we have detected
      gelatinase A in the cytoplasm of fibroblasts and at the surface of the tumor
      cells. This membrane localization of the protein could result from its binding,
      following secretion by the neighbouring stromal cells, to a specific binding site
      expressed at the surface of the carcinoma cells. These cells are indeed able to
      induce an increased proteolytic activity by enhancing the transcription of these
      enzymes by peritumoral fibroblasts. These enzymes represent therefore potential
      targets for the development of new therapeutic strategies.

PMID- 9532866
TI  - Severe colonic complications in acute pancreatitis.
AB  - BACKGROUND: Colonic complications in patients with acute pancreatitis may be very
      severe and have rarely been analyzed in Chinese patients. METHODS: We
      retrospectively evaluated 1,637 patients with acute pancreatitis who were
      admitted to the Veterans General Hospital-Taipei from January 1986 to December
      1995 in order to identify those with severe colonic complications. The clinical,
      radiologic and pathologic features and surgical findings in these patients are
      reviewed. RESULTS: Eight of 1,637 patients with acute pancreatitis had severe
      colonic complications. Six of them were diagnosed between two and eight weeks
      after the onset of clinical pancreatitis. All had a Ranson's score of at least 3.
      Four patients, including one with hematochezia, had a strong positive reaction
      for occult blood in stool specimens. Computed tomography (CT) revealed
      necrotizing pancreatitis and colonic wall swelling in all eight patients. Colonic
      involvement was discovered by CT in two patients prior to surgery, one with
      colocutancous fistula and the other with colonic perforation. The other six
      patients were found to have colonic involvement incidentally at the time of
      laparotomy. All of the colonic involvements were located near the splenic
      flexure. In addition to necrosectomy, three patients underwent segmental
      hemicolectomy and the remaining five patients had simple closure of the
      perforation. Diverting loop ileostomy or colostomy was also carried out in all
      patients. Three patients (34%) died of overwhelming sepsis superimposed on the
      subsequent multiple organ failure between 44 and 122 days after the onset of
      pancreatitis. CONCLUSIONS: Severe colonic complications of acute pancreatitis are
      rare. Although preoperative diagnosis is difficult, CT may be helpful to make an
      early diagnosis. These complications should be suspected in patients with severe
      acute pancreatitis when acute lower gastrointestinal hemorrhage or positive stool
      occult blood is found two to eight weeks after the onset of pancreatitis or when
      CT reveals necrotizing pancreatitis and colonic wall swelling; this will allow
      early surgical intervention.

PMID- 9532867
TI  - Glaucoma following congenital cataract surgery.
AB  - BACKGROUND: Glaucoma is a well known complication that arises after congenital
      cataract surgery. The purpose of this research was to study eyes that manifested
      glaucoma after congenital cataract surgery and to identify associated factors.
      METHODS: A retrospective review of patients who received cataract surgery before
      the age of five was conducted. The chi-squared test for association was used to
      evaluate risk factors. RESULTS: One hundred and forty eyes of 85 patients were
      studied. Nineteen eyes of 12 patients had glaucoma, among which 79% was open
      angle. Patients who underwent secondary membranectomy for visual axis occlusion
      had a higher risk of glaucoma, especially when secondary membranectomy was
      performed within one year of primary surgery. Of eight eyes with microcornea,
      none developed glaucoma after surgery. No significant difference in outcome was
      found among the surgical methods of cataract removal. CONCLUSIONS: Aggressive
      clearance of lens cortex during surgery is important. Secondary membranectomy for
      clearing the visual axis occlusion is associated with post operative glaucoma.
      Frequent and long-term patient follow-up is mandatory since glaucoma may manifest
      many years after congenital cataract surgery.

PMID- 9532868
TI  - Incidental renal cell carcinoma: pathologic features and survival rate.
AB  - BACKGROUND: The aim of this study was to compare outcomes in patients with
      symptomatic and incidental renal cell carcinoma (RCC). METHODS: From October 1982
      to December 1996, 200 patients with RCC were enrolled in this study. Their
      medical records were reviewed for symptoms, tumor stage, and lymph node and
      metastatic status. Symptomatic and incidental RCCs were compared by the overall
      survival rate of patients. The survival rate was determined by the Kaplan Meier
      method. Log rank testing was used to analyze the statistical difference in the
      survival period between both groups. RESULTS: The proportion of incidental RCC
      was 21% (42/200). The majority of cases (73.8%) were diagnosed primarily by
      abdominal ultrasonography. Incidental RCCs were smaller in size than symptomatic
      RCCs (5.1 +/- 2.0 cm vs. 7.5 +/- 1.8 cm, p = 0.001). Incidental RCCs were of a
      lower stage, and patients with incidental RCCs had significantly longer overall
      survival rates than those with symptomatic RCCs (p < 0.001). CONCLUSIONS:
      Ultrasonography is a useful tool for the detection of incidental RCC. Improvement
      in the overall survival rate of incidental RCC patients suggests that when these
      tumors are identified earlier, treatment results are better.

PMID- 9532869
TI  - Lymph node metastasis in squamous cell carcinoma of the intrathoracic esophagus.
AB  - BACKGROUND: In esophageal carcinoma lymph node metastasis is one of the most
      important factors of prognosis. This prospective study evaluated the incidence
      and extent of lymph node metastasis, and assessed the relationship between the
      depth of tumor invasion and lymph node metastasis in esophageal carcinoma.
      METHODS: Between 1985 and 1996, tissue samples from 112 patients undergoing
      radical esophagectomy and gastric substitution for squamous cell carcinoma of the
      intrathoracic esophagus were collected. Patients with distant organ metastasis
      were excluded. All specimens were evaluated and sent for histopathologic
      examination. RESULTS: In 108 men and four women with a mean age of 63.1 years,
      the average number of dissected lymph nodes in one surgical procedure, was 30 per
      person. The most commonly involved nodes were the periesophageal (42.9%) and the
      perigastric (42.9%) nodes, followed by the recurrent laryngeal nerve (23.8%) and
      thoracic paratracheal (22.2%) nodes. For tumors in the upper third of the
      esophagus, the most frequently involved nodal groups were the periesophageal
      (28.6%) and the paratracheal (28.6%) nodes, followed by the recurrent laryngeal
      nerve (21.4%) the deep cervical (21.4%), and the perigastric (21.4%) nodes. For
      tumors in the middle third of the esophagus, the periesophageal nodes (27.3%)
      were most commonly involved, followed by the perigastric (18.2%) and the
      subcarina (10.6%) nodes. For tumors in the lower third of the esophagus, the
      perigastric lymph nodes (37.5%) were the most common nodal metastatic site,
      followed by the celiac (18.8%) and the recurrent laryngeal nerve (18.2%) nodes.
      Depth of tumor invasion was also found to correlate significantly with lymph node
      metastasis (p = 0.0015). CONCLUSIONS: Wide lymph node metastasis between the neck
      and the upper abdomen occurs frequently in squamous cell carcinoma of the
      esophagus. For potentially curable esophageal carcinomas, en-bloc esophagectomy
      with complete locoregional lymph node dissection may provide favorable local
      control of the lesion and more accurate tumor staging.

PMID- 9532870
TI  - Acute pancreatitis in pregnancy.
AB  - BACKGROUND: Acute pancreatitis in pregnancy is rare. Our purpose in this study
      was to discuss the etiology, incidence and course of pancreatitis in pregnancy
      and to evaluate the maternal and perinatal outcomes. METHODS: Pregnant women with
      pancreatitis admitted to China Medical College Hospital, Taiwan, from 1980 to
      1995 were studied retrospectively. A total of 16 patients were enrolled in the
      study. Two patients had gallstones and hyperlipidemia; four had gallstones alone;
      seven had hyperlipidemia alone; one had gestational diabetes mellitus; one had
      hyperparathyroidism and pregnancy-induced hypertension alone; and one had
      Hashimoto's thyroiditis. Conservative treatment and low-fat diets were
      administered to the patients. RESULTS: The incidence of gestational pancreatitis
      in this series was one in 6,790 pregnancies. The fetal outcome included eight
      preterm deliveries and three fetal losses. There were no maternal mortalities.
      The etiologies of pancreatitis were primary hyperlipidemia (56.3%) and gallstones
      (37.5%). All patients responded favorably to supportive therapy, and most of the
      symptoms subsided after delivery. CONCLUSIONS: Early diagnosis and treatment is
      of utmost importance in the management of acute pancreatitis in pregnancy. The
      results of this study showed good maternal outcome following appropriate
      treatment. Fetal prognosis was less favorable and was most often associated with
      hyperlipidemia. Fetal monitoring is essential during the management of
      pancreatitis in pregnancy.

PMID- 9532871
TI  - Symptomatic patent ductus arteriosus in very low birth weight infants.
AB  - BACKGROUND: Premature neonatal survival rates have increased significantly. The
      diagnosis of patent ductus arteriosus (PDA) has also increased. In this paper, we
      present our experience of incidence, clinical features and outcome of the
      treatment of symptomatic PDA in very low birth weight infants. METHODS: From
      January 1990 to December 1995, 181 premature infants with birth weight less than
      1,500 g were admitted to the Neonatal Intensive Care Unit (NICU) of Veterans
      General Hospital-Taipei. Thirty-seven were diagnosed to have symptomatic PDA. By
      reviewing hospital records, the clinical features and outcome of treatment of
      these infants were analyzed retrospectively. RESULTS: The incidence of
      symptomatic PDA was 20.9% and 21.4% in infants with birth weight less than or
      equal to 1,000 g, 1,001-1,500 g, respectively. The mean age at diagnosis of
      infants with symptomatic PDA was significantly less than those without symptoms
      (3.6 +/- 2.9 days vs 9.6 +/- 17.2 days, p = 0.044, 95% CI = 0.2-11.8). With fluid
      restriction and diuretic therapy, asymptomatic patients had a higher spontaneous
      ductal closure rate than symptomatic patients (58.3% vs 10.8%, p < 0.001, 95% CI
      = 17.9-77.1%). Thirty-two (97.0%) infants with symptomatic PDA responded to
      indomethacin therapy. However, four infants (12.1%) had recurrence. These four
      infants and a nonresponder received surgical ligation of the PDA and survived.
      There were four deaths. The reasons for death were respiratory failure in two,
      sepsis in one and necrotizing enterocolitis with intestinal perforation in one.
      CONCLUSIONS: Conservative medical management such as fluid restriction and
      diuretics are often adequate for asymptomatic PDA. However, since symptomatic PDA
      tends not to close spontaneously, patients should be treated with indomethacin if
      ductal shunting compromises cardiopulmonary function.

PMID- 9532872
TI  - Bilateral choroidal metastases as the initial presentation of a small breast
      carcinoma: a case report.
AB  - Most ocular tumors metastasize from systemic origins in breast carcinoma in
      females, and bronchial carcinoma in males. Here, we report a case of choroidal
      carcinoma metastasis from the breast with visual problems being the only initial
      manifestations. In this case, both eyes were involved at almost the same time,
      with initial manifestation of blurred vision which progressed to complete visual
      loss. At first, the patient was diagnosed with malignant melanoma, and
      enucleation of the right eye was performed in another hospital. However, the
      tumor had already metastasized rapidly to numerous organs, including the lungs,
      brain and bone, although it had not affected the liver. Clinical presentations
      were, therefore, not compatible with those of malignant melanoma, which has
      usually been reported to metastasize to the liver. Persistent hypercalcemia and
      raised carcinoembryonic antigen (CEA) concentrations prompted investigations into
      the possibility of systemic malignancy. A very small breast nodule was finally
      located by thorough physical examination, and a lumpectomy was performed. A
      detailed review of the histopathology showed the tumors from the breast and the
      right eye to have the same origin. Simultaneous bilateral choroidal metastases
      from other malignancies is not uncommon; however, it is quite rare for breast
      carcinoma to present with visual problems as a first manifestation. Detailed
      history taking and physical examination are therefore essential when searching
      for a primary tumor, so that appropriate therapy can be given earlier.

PMID- 9532873
TI  - Multifocal retroperitoneal malignant fibrous histiocytoma: a case report.
AB  - This report concerns a 67-year-old male with malignant fibrous histiocytoma
      arising from the psoas muscle and perirenal soft tissue. The tumor was considered
      a mesenchymal neoplasm. These are generally clinically and radiologically
      indistinguishable from other retroperitoneal tumors. This patient received en
      bloc resection of the retroperitoneal tumor and radical nephrectomy without
      adjuvant therapy. He underwent excision of a retroperitoneal cystic mass
      complicated with lymph leakage one year postoperatively. Discharged in a stable
      condition after one week of total parenteral nutrition, the patient remains
      disease-free 16 months postoperatively.

PMID- 9532875
TI  - Placenta previa accreta with cervical involvement causing tenacious postpartum
      hemorrhage: a case report.
AB  - Conservative treatment for placenta accreta has recently been popularly accepted
      even though serious postpartum hemorrhage, resulting in maternal death, may
      occur. We report a case of placenta previa accreta with cervical involvement
      resulting in tenacious postpartum hemorrhage. A 28-year-old pregnant woman,
      gravida-2 para-1, who had undergone a previous cesarean section, was scheduled
      for a repeat cesarean section because of complete placenta previa associated with
      placenta accreta. The patient underwent cesarean section and delivered a 3,700 g,
      male infant. Manual removal of the placenta was performed with some difficulty
      and redundant placental tissue remained adhered to the uterine wall. Oxytocin,
      ergometrine, uterine arterial ligation and packing of the lower uterine segment
      were used to control bleeding; the wound was closed as usual after achieving
      adequate hemostasis. While closing the abdominal wall, vaginal bleeding was
      noted. After conservative treatment, shock progressively emerged due to
      persistent vaginal bleeding. Emergency laparotomy found active bleeding from the
      cervix and total abdominal hysterectomy was performed without hesitation. Careful
      evaluation is mandatory to preserve the uterus. In the case of cervical
      involvement, aggressive treatment such as hysterectomy should be undertaken
      promptly to decrease the risks of both morbidity and mortality.

PMID- 9532874
TI  - Neonatal myocardial infarction: a case report.
AB  - Neonatal myocardial infarction is a rare disorder. It occurs in association with
      congenital heart disease or coronary artery abnormalities. In the absence of
      structural heart disease, perinatal asphyxia and coronary artery thromboembolism
      have been reported as common etiologies. Whether the Coxsackie B viral group has
      a causal role in adult myocardial infarction remains controversial. We report
      herein a case of neonatal myocardial infarction without known congenital heart
      disease, in whom perinatal Coxsackie B viral infection was suspected to be the
      underlying cause. However, definite evidence indicating a causal relationship
      between neonatal myocardial infarction and Coxsackie B viral infection was
      lacking in this case.

PMID- 9532876
TI  - [Presidential address, 1997].

PMID- 9532877
TI  - [Laparoscopic and laparoscopically-assisted radical hysterectomy].

PMID- 9532878
TI  - [Fetal fibronectin in cervico-vaginal secretions: prediction of premature and
      term delivery].

PMID- 9532879
TI  - [Male infertility...when to stop...].

PMID- 9532880
TI  - [Indications for hysterectomy].

PMID- 9532881
TI  - [Environment and spermatogenesis].
AB  - An alteration of the male reproductive system as well as regional differences in
      this alterations were recently reported in several studies. That suggest a
      relationship between environmental conditions and spermatogenesis. Histories of
      dibromochloropropane distilbene and gossypol are indicative of the influence of
      occupational and drug exposure, or of the life style on the male reproductive
      tract. The present review deals with chemical (pesticides, metals ...), physical
      (ionising and non-ionising radiation's, endogenous heat) and life style factors
      (exogenous heat, posture, clothing, alcohol, tobacco, stress, sport, nutrition)
      susceptible to have a deleterious effect on spermatogenesis. Besides, the
      hypothesis of endocrine disrupters is discussed with inclusion of the information
      of regional differences from recent studies. While further studies are required
      to precisely determine the function of the quoted factors in the secular decrease
      and regional variations of spermatogenesis, it is suggested that sperm is an
      indicator of public health and that the principle of precaution is to be
      considered with the usual implication: 1) effective preventive action in
      occupational world, 2) avoiding of a risk factor discovered during infecondity
      consulting, 3) non use of substances which innocuity is not proved by toxicologic
      studies in animals.

PMID- 9532882
TI  - [Reproduction techniques and infectious risks: study of practices in French
      centers in 1997].
AB  - In the absence of specific legislation or consensual recommendations in France
      regarding the routine screening of infectious transmissibility risk before intra
      couple medically assisted procreation (MAP), an inquiry about the practice of
      screening management in France has been performed. 500 questionnaires were sent,
      and 104 answers were received. The results of such inquiry coming from 62 private
      and 42 public centers are the subject of this paper.

PMID- 9532883
TI  - [Voluntary abortion: new perspectives in local anesthesia].
AB  - New perspectives have been envisioned for the TOP instrumental technique, through
      the utilization of pharmacologic products, whose property is to dilatate the
      cervix. Misoprostol or mifepristone, when administrated to a patient a few hours
      before a TOP by uterine suction curettage, enables a dilatation of the cervix in
      such a way that it allows the surgically induced abortion to be carried out with
      local anesthesia, under optimal comfort conditions for the patients as well as
      for the operator.

PMID- 9532884
TI  - [Limits of ambulatory medical treatment of ectopic pregnancies by intramuscular
      methotrexate: prospective study on 54 patients].
AB  - OBJECTIVE: To evaluate the limits of ambulatory treatment of ectopic pregnancy
      with an intramuscular injection of 50 mg/m2 methotrexate. METHOD: Non randomised
      prospective study from october 1993 and april 1996 at Poissy Hospital. 100
      ectopic pregnancies were diagnosed: 54 were treated medically and 46 had a
      surgical treatment. RESULTS: The mean hCG for the ectopic pregnancies treated
      medically was 7,273 Ul/ml +/- 12,548 (90-68,220), an ectopic mass was seen in 74%
      and to precise the diagnosis a currettage was done in 24 cases (44%) if the
      initial hCG was below 2,000 Ul/ml. The medical treatment was a success for 37
      (68.5%) ectopic pregnancies with a mean time of resolution of hCG of 31.9 days +/
      18 (4-90) (with a positive correlation between initial hCG titer and time to
      resolution of 0.5, p = 0.001). For 15 (27%) patients a second dose of
      methotrexate was necessary with a 73% success rate and 17 (32%) patients were
      operated (8 salpingectomies). Sixteen of 20 (80%) demonstrated tubal patency at
      follow-up hysterosalpingogram and within 7.5 +/- 4 months 26 of 30 (87%)
      conceived and there was no recurrence of ectopic pregnancy. CONCLUSIONS: The
      medical treatment of ectopic pregnancies with methotrexate has its limits. In our
      series, if we treat ectopic pregnancies without cardiac activity, with a mass
      below 35 mm and a hCG below 10,000 Ul/ml the success rate is 81%.

PMID- 9532885
TI  - [Intra-uterine contraception: will progress come from where we expect?].

PMID- 9532886
TI  - [Effects of nomegestrol acetate administered alone or with cutaneous 17 beta
      estradiol in inversed sequence on cycle quality and hot flashes in
      periomenopausal women].

PMID- 9532887
TI  - [Peritoneal-tubal bilharziasis found during a cesarean section in the gynecologic
      and obstetric clinic in the University Hospital Center of Aristide Le Dantec].

PMID- 9532888
TI  - [Brachial plexus obstetric paralysis (20 cases): obstetric data and post-natal
      prognosis].

PMID- 9532889
TI  - [Pathogenesis of atherosclerosis in the 21st century (review of the literature)].

PMID- 9532890
TI  - [Rapid method of measuring angiotensin converting enzyme activity in blood].
AB  - A simple and rapid spectrophotometric procedure is developed for measuring the
      activity of angiotensin-converting enzyme (ACE) in human serum. Furylacryloyl
      phenylalanyl-glycyl-glycine (FAPGG) possessing a high absorption capacity at 334
      nm was used as the substrate. ACE hydrolyzes FAPGG and decreases the extinction.
      The level of extinction drop is the measure of ACE activity. Optimal parameters
      of the enzymatic reaction are defined, including medium pH, substrate
      concentration, and volumes of the sample and inhibitor of ACE activity. Adequate
      control permits monitoring the interference of exogenic and endogenic factors in
      ACE activity in the studied sample. The proposed method is available for clinical
      laboratories, easily reproducible, and sufficiently sensitive.

PMID- 9532891
TI  - [Lacrimal and salivary antioxidants in viral infection].
AB  - The activities of antioxidant enzymes in the cornea and tears in patients with
      ophthalmic herpes and in the saliva in those with herpetic stomatitis were
      assessed. Impaired inhibition of hydroxy radical and a drop of antioxidant
      enzymes activities and of the level of ascorbic acid in herpes-infected cornea
      and tears are factors in the pathogenesis of ophthalmic herpes. Measurements of
      enzymatic activities in the tears and saliva in herpetic infection are a valuable
      diagnostic test and a criterion of treatment efficacy.

PMID- 9532892
TI  - [Gas chromatography of organic acids: methodological and diagnostic aspects].
AB  - Gas liquid chromatography (GLC) remains the most efficient method for analysis of
      organic acids in biological fluids. This paper presents a GLC method for
      measuring organic acids in the urine. Our method of extraction and GLC of
      trimethylsilyl derivatives of organic acids is a specific and highly sensitive
      procedure which permits investigation of the complex spectrum of organic acids,
      including aliphatic oxocarbonic, dicarbonic, hydroxycarbonic, and aromatic acids
      and glycine conjugates in the urine and other physiological fluids. It can be
      used for the diagnosis and prenatal screening of hereditary and acquired
      metabolic disorders.

PMID- 9532893
TI  - [Significance of ceruloplasmin measurements in laboratory diagnosis of chronic
      prostatitis].

PMID- 9532894
TI  - [Prenatal diagnosis of fetal hypoxia based on lipid peroxidation values in
      exhaled air condensate].
AB  - Lipid peroxidation values were measured in the serum and expired air of pregnant
      women. The levels of diene conjugates, secondary intermediates of free-radical
      processes, and malonic dialdehyde were increased in exhaled air condensate of
      pregnant women who gave birth to babies with grave hypoxia, as against women with
      healthy babies or babies with slight hypoxia. All the studied values were more
      demonstrative in the expirate than in the serum. Hence, grave fetal and neonatal
      hypoxia can be diagnosed before delivery by examining the exhaled air condensate
      of pregnant women.

PMID- 9532895
TI  - [Possibility of stabilizing urea in preparation of control specimens].
AB  - 9-Triphenylphosphoniomethylphenanthrene chloride (9-TC) is a highly effective
      antibacterial biochemical stabilizer of the urea, which, used in concentrations
      0.6 to 2.45 mmoles/liter, stabilizes its content in the serum for 990 days.
      Control specimens are prepared as follows: 100 ml of human or animal blood serum
      is added to 900 ml of 1.82 mmole aqueous solution of 9-TC, mixed, 24 h stored at
      4-8 degrees C, and centrifuged. The resultant centrifugate is used as reference
      specimen for controlling urea measurements by the diacetylmonoxime method.

PMID- 9532896
TI  - [Non-flame atomic absorption method of the analysis of mercury-containing
      biological materials].
AB  - Julia-2 mercury analyzer is modified. Gasodynamic scheme of the device is
      altered: water vapors can no longer enter the cuvette, the circulation mode is
      realized. Equilibrium concentration of mercury vapors is thus attained. The
      analytical signal is well reproduced. Alteration of the reactor volume improves
      the sensitivity of testing larger samples.

PMID- 9532897
TI  - [Features of laboratory diagnosis in geriatrics].

PMID- 9532898
TI  - [Methods of in vitro assessment of the degree of complement activation by the
      classical pathway].
AB  - A sensitive a simple method is proposed for assessing the complement activation
      degree by the monospecific classical route. The alternative pathway of the
      complement activation proposed by Adachi et al. in 1990 is taken account of. The
      specific features of the proposed method are 1) use of commercial dry complement
      of guinea pigs with the regulatory protein defect needed for the alternative
      pathway of complement activation; 2) absence of EGTA in GVB and presence of Ca2+;
      3) use of sensitized sheep red blood cells as the target cells. These conditions
      prevent the alternative pathway of complement activation and permit only the
      classical pathway. Effects of some drugs on the classical pathway of complement
      activation by the new method and on Adachi's alternative method are investigated.
      Estradurin and fosfestrol affect the complement activation by both pathways.

PMID- 9532899
TI  - [Cytomorphological diagnosis of granulosa cell tumor of the ovary].
AB  - The cytology of granulosa cell tumor in children and adults is studied.
      Cytological smears of ascitic fluid and fresh tissue smears were examined. The
      tumor was diagnosed in 9 patients aged 11 to 73 years. All patients had symptoms
      of hyperestrogenia. Adequate treatment of the condition requires the tumor to be
      differentiated from other tumors (thecoma, low-grade and small-cell carcinomas,
      carcinoid, yolk-sac tumor, and lymphoma) before or during surgery.

PMID- 9532900
TI  - [A new rapid automated photometric method in analysis of quantitative indicators
      of food product contamination].
AB  - Thirty-five specimens of pasteurized milk were tested for bacterial contamination
      by rapid autocalibration photometry for liquid, semiliquid, and homogenized hard
      foodstuffs, developed by the Ecotest Firm, Russia. Photometric (turbidimetric)
      analysis was carried out using the Labsystems (Finland) iEMS Reader plate
      photometer and Russian Analitika BACT software. The results of traditional
      analysis and the new rapid method developed by Ecotest were in good correlation,
      the differences did not surpass the magnitude of errors of measurements. The new
      method takes just 10-15 h instead of the routine 72 h and requires 300 times less
      nutrient media.

PMID- 9532902
TI  - [Method of quantitative assessment of antimicrobial effects of iodine-containing
      preparations].
AB  - Iodine-containing preparations were studied by UV spectral analysis. Water
      soluble composition of 1,3-diethylbenzimidasolium triiodide is inactivated in the
      presence of meat-peptone broth. Dissolving of these preparations in a mixture of
      acetone and stearic acid does not change the physicochemical properties or impair
      the antibacterial effect. A high antibacterial effect of 12 iodine-containing
      compounds has been demonstrated: 15-min exposure suppressed the growth of
      bacteria at the minimal concentration of 0.1-1.0 microgram/ml.

PMID- 9532901
TI  - [Use of polymerase chain reaction in clinical diagnostic laboratories in viral
      hepatitis B and C].
AB  - HBV and HCV markers were detected in the blood serum of patients with acute and
      chronic hepatitis B (HCV), chronic hepatis C (HCV), and acute nonA, non-B, non-C
      hepatitis by enzyme immunoassay and the polymerase chain reaction (PCR) in order
      to assess the clinical value of PCR for the diagnosis of HBV and HCV and monitor
      the antiviral roferon A therapy in patients with HCV. HBV DNA was detected by the
      PCR in 100% of acute HBV patients and in 65.7% of chronic HBV patients. In
      chronic HCV, the PCR detected HCV RNA in 71% of cases. After roferon A therapy,
      HCV RNA was no longer detected in 43.2% of PCR-positive patients. PCR is
      recommended for the diagnosis of acute and chronic HCV, selecting the patient
      groups, and assessing the efficacy of specific therapy.

PMID- 9532903
TI  - [Rational use of measurements and observations in clinical laboratory diagnosis].
AB  - Clinical chemistry possesses sufficient methodologies to ensure a fast transition
      between research and potential usefulness of measurements to be used in
      diagnosis. This is the case with future methods, such as DNA and RNA assays. The
      major challenge for the future is to develop methods that can ensure clinical
      performance and clinical efficacy of measurements potentially useful for the
      diagnosis, so as to select the still useful routine methods and refuse from the
      irrational ones.

PMID- 9532904
TI  - [Documents of Canadian standards].

PMID- 9532905
TI  - [Ischemic heart disease in the elderly and senile patients: clinical
      presentation, diagnosis, treatment, prevention].

PMID- 9532906
TI  - [Relationship between activity of atrial natriuretic peptide and process of
      myocardial remodelling in patients with cardiac failure].
AB  - Echocardioscopy in M- and B-modes with measurement of routine parameters of
      central hemodynamics and thickness of carotid intimal-medial segment as well as
      radioimmunoassay of plasma concentrations of atrial natriuretic peptide (ANUP)
      were performed in 159 patients aged 42-63 years (17 healthy subjects and 142
      patients with cardiac failure associated with ischemic heart disease and sinus
      rhythm, without history of myocardial infarction). The results were indicative of
      possible use of ANUP as a marker of initial cardiac insufficiency and a corrector
      of the disease prognosis.

PMID- 9532907
TI  - [Hemostasis and antithrombotic therapy in massive thromboembolism of pulmonary
      artery].
AB  - The results of treatment are reviewed for 114 patients with massive
      thromboembolism of the pulmonary artery in respect to antithrombolytic measures
      and initial condition of hemostasis. Prognostic hemostasiological criteria of
      tolerance and relative resistance of the patients to streptokinase preparations
      and optimal thrombolytic methods in massive thromboembolism of the pulmonary
      artery are determined.

PMID- 9532908
TI  - [Characteristics of histocompatibility antigens distribution in patients with
      multiple sclerosis].
AB  - Distribution of antigens HLA was characterized in 84 Azerbaijan patients with
      multiple sclerosis. Compared to controls, antigens DR2 and DR4 occurred in the
      patients more frequently, while determinant B35 less frequently. In remittent and
      progressive disease antigens A2, B12 and A3, B7 were encountered more frequently,
      respectively.

PMID- 9532909
TI  - [Lipoprotein(a) in systemic lupus erythematosus].

PMID- 9532910
TI  - [Diagnostic and prognostic significance of some parameters of nonspecific defense
      humoral mechanism in patients with lymphedema complicated by erysipelas
      inflammation].
AB  - Immunological investigation of 193 patients with uncomplicated lymphedema and
      lymphedema complicated with erysepalas inflammation registered in the patients
      with inflammation high levels of antigen-nonspecific circulating immune
      complexes, beta-lysins, alpha1-antitripsin, serum IgE and IgM in the presence of
      massive bacterial infection of the limb skin. The above alterations may serve
      diagnostic and prognostic indicators of the disease chronicity and progression in
      patients with lymphedema.

PMID- 9532911
TI  - [Effects of mono- and combined peptic ulcer therapy on lipid peroxidation and
      antioxidant defense in ulcerous zone].
AB  - Lipid peroxidation and antioxidant activity in the margin and periulcerous zones
      of duodenal mucosa were investigated in 111 patients with duodenal ulcer before
      treatment and in periscar zone after chemotherapy allowing for Helicobacter
      pylori infection. In active ulcer lipid peroxidation was high while antioxidant
      activity was depressed. Helicobacter pylori was found able to initiate
      peroxidation. Pathogenetic therapy including antihelicobacter drugs inhibits
      activity of lipid peroxidation and promotes normalization of antioxidant activity
      of duodenal mucosa. This gives grounds for combined use of antisecretory and
      antichelicobacter medicines.

PMID- 9532912
TI  - [Traumatic disease: clinico-pathogenetic, diagnostic and prognostic significance
      of hemostatic changes].

PMID- 9532913
TI  - [Renin-aldosterone system in secretion of cortisol in patients with arterial
      hypertension in European North].
AB  - Renin activity (RA), concentration of aldosterone and hydrocortisone in plasma
      were measured by radioimmunoassay in 78 males with arterial hypertension living
      in the Far North. RA and aldosterone concentrations were high in patients with
      borderline arterial hypertension irrespectively of hemodynamic type of the
      disease. Hydrocortisone levels in them were normal. In hypertension stage I and
      II RA and hydrocortisone concentrations were normal, while aldosterone levels
      have risen. Renin-aldosterone index showed high RA in all hemodynamic types of
      hypertension.

PMID- 9532914
TI  - [Endemic goiter in the extreme North of West Siberia].
AB  - Random examinations covering 8-60-year-old 4345 citizens of 12 settlements of the
      Yamal-Nenets Autonomic Territory discovered goiter endemia throughout the
      territory but most evident the endemy manifested in the Far North. The prevalence
      of endemic goiter among schoolchildren made up 52.8% (enlargement of the goiter
      of the 1st and 2nd degree), among adults-49.2%. By ultrasound investigation, the
      above percentages were 29 and 26.4%, respectively. This corresponds to moderate
      endemia. The median of urinary iodine excretion averaged in the territory 5.1
      micrograms%, while overall iodine insufficiency (number of children with urinary
      iodine < 10 micrograms%) was 81.9%. In the Far North iodine excretion was less
      but goiter incidence was higher than normal. Thus, in the Far North goiter
      endemia is rather serious.

PMID- 9532915
TI  - [Combination of cyclosporin and ketoconazole in immunosuppression schemes in
      patients with transplanted kidney].
AB  - Ketoconazole was used as an adjuvant to conventional 3-component
      immunosuppression in 56 patients with transplanted kidney. While receiving
      ketoconazole postoperative patients can be given reduced doses of cyclosporin
      (1.5-2 times). Long after the operation cyclosporin doses can be reduced 3-4
      fold. Acute rejection occurred less frequently. This means that reduced
      cumulative steroid dose is needed for management of the rejection. In the dose
      above 100 mg/day, ketoconazole is able to enhance nephrotoxic effect of
      cyclosporin. A complication--acute renal dysfunction--is attributed to iatrogenic
      hypoaldosteronism induced by combination of large-dose cyclosporin +
      ketoconazole.

PMID- 9532916
TI  - [Carnitine and solcoseryl in combined treatment of elderly and senile patients
      with myocardial infarction].

PMID- 9532917
TI  - [Rheumatoid arthritis in children: modifying effect of cyclosporin A].

PMID- 9532918
TI  - [Current approaches to diet therapy of malabsorption syndrome].

PMID- 9532919
TI  - [Clinical and occupational prognosis in myocardial infarction patients which were
      on different activation regimens and stayed in hospital for different time].
AB  - Two groups of patients with Q and non-Q myocardial infarction were compared: 105
      patients who underwent early activization and were discharged early and 82
      patients treated according to the routine 3-5-week program. The activization
      implied physical rehabilitation which took 2 times less time than the standard
      one. It is shown that disability of patients rehabilitated for shorter period of
      time was significantly shorter. The criteria allowing shorter hospitalization for
      myocardial infarction patients are proposed.

PMID- 9532920
TI  - [A case of pulmonary artery thrombosis due to catheterization of right subclavian
      vein in female patient with myocardial infarction].

PMID- 9532921
TI  - [Clinical training of physicians at the middle-age universities].

PMID- 9532922
TI  - [Medical terms and their relevance to art and literature].

PMID- 9532923
TI  - [75th anniversary of the journal, Occupational Medicine -- Occupational Medicine
      and Industrial Ecology].

PMID- 9532924
TI  - [New aspects of carcinogenic hazards in shoe industry (a retrospective
      epidemiological study)].
AB  - Epidemiologic study of occupational cancer covered a cohort of shoe production
      workers exposed to chloroprene. The cohort consists of 5058 examinees having
      length of service over 2 years and subjected to follow-up for 15 years. The total
      person-years equaled 75,000. The examinees demonstrated higher mortality with
      liver cancer, leukoses, pancreatic carcinoma, malignancies of central nervous
      system, renal cancer. The study first revealed unusual but significant risk of
      mortality with malignancies of mediastinum and heart (ICD-12 code is 164). The
      study defined a "dose-effect" correlation between exposure to chloroprene and
      death with liver cancer.

PMID- 9532925
TI  - [State of local immunity under exposure to anthropogenic factors of biological,
      chemical and physical nature in industry].
AB  - The authors studied immunologic features of saliva in 1714 workers exposed to
      vibration and other occupational hazards in microbiologic, chemical enterprises.
      The examinees demonstrated lower activity of lysozyme and concentrations of IgA,
      higher levels of IgG. Immunologic features of saliva was proved to have extreme
      diagnostic importance, therefore could be used to detect early signs of exposure
      to occupational hazards and to diagnose pathologic conditions caused by those
      hazards.

PMID- 9532926
TI  - [Immune status of workers at a hydrolysis yeast plant].
AB  - The clinical and immunologic study involving a complex of immunologic parameters
      covered 52 workers of yeasting hydrolysis production. The results are--depression
      of cellular immunity with modified T-cellular membranes; inhibited phagocytic
      activity of neutrophils and increased expression of E-receptors; disbalanced
      saliva immune factors; sensibilization to fungus producing hydrolysis yeast. The
      study revealed immune features varying with degree of exposure to the
      occupational materials, with length of service and health state of the examinees.
      Those features could be valuable for arrangement of prophylactic measures.

PMID- 9532927
TI  - [Review of articles of the Journal of Occupational Medicine, 1994-1995].

PMID- 9532928
TI  - [Biological testing of cyclic acetaldehydes and their oxidation products using
      mollusks].
AB  - Toxicity of cyclic acetaldehyde and the affined compounds was studied in
      freshwater shellfish Planorbis spirorbis in laboratory conditions. Chronic
      threshold concentrations of the acetaldehyde appeared to depress the increase in
      total mass and to lower the content of hemolymph. Functional state of the
      shellfish cells changed--the share of cell deformations reaches 57%. The
      phenomena are traced to disorders in hemocytes membrane permeability, changes in
      cellular composition of hemolymph, decreased share of basophilic and increased
      share of oxyphilic cells in hemolymph. Thus, studies of toxicity should include
      both traditional examination and thorough hematologic evaluation.

PMID- 9532929
TI  - [Evaluation of the effects of chlorophenol-free wood antiseptics in experimental
      animals].
AB  - The authors report on creation of domestic chlorophenol-free preservatives for
      wood (EOK, K-12, Katan) in Arkhangelsk Research Institute. Application of those
      chemicals is cheaper than that of foreign analogs. Toxicity of the preservatives
      was evaluated according to morphologic and functional changes in various organs
      and systems of experimental animals which faced long exposure to the
      preservatives. The experiments proved K-12 to be the most pathogenic among
      others. EOK preservative fails to induce severe pathologic changes in
      experimental animals, demonstrated no cumulation and allergy. Katan takes
      intermediate place between those two.

PMID- 9532930
TI  - [Importance of variation criteria in statistical evaluation of the immune status
      of work crews].
AB  - Variation criteria--variation coefficient, Fisher criterion (F-value) and
      suggested by the authors index of homeostasis--enable to evaluate completely the
      state of occupational crews and reveal their compensated disadaptation.
      Administration of adaptogens (such as oxymethacil) is expedient for correction of
      premorbid conditions in occupational crews. Increased aboriginality and random
      selection during occupational activities considerably better adaptational
      characteristics of the occupational crews.

PMID- 9532931
TI  - [An experimental study of lipid peroxidation processes and antioxidant protection
      in exposure to isosorbide-5-nitrate].

PMID- 9532932
TI  - [Experimental substantiation of maximum allowable concentration of pesticide
      sulfocarbathion K in the workplace air].

PMID- 9532934
TI  - [Use of stent-nephrostomy in the treatment of renal transplant urologic
      complications by percutaneous surgical techniques].
AB  - Ureteral complications including stricture of the ureter and necrosis of the
      ureter with urinoma are the most frequent urological complications after renal
      transplantation. About 1-12% of recipients suffer from these complications.
      Percutaneous techniques allow correction of ureteral complications by less
      traumatic than open surgical operations and sufficiently effective method.
      Ureteral complications were registered in 20 cases (3.6%) out of 561 renal
      transplantations carried out in our institute from 1990 to 1995. Only in 5 cases
      open surgical correction was necessary, 15 patients after percutaneous
      nephrostomy underwent bougienage and/or balloon dilatation of ureter with further
      antegrade stenting. In all percutaneous operations special stent-nephrostoma
      developed in our department was used. Use of the stent-nephrostoma with its
      further transformation into the ureteral stent has some substantial advantages
      versus routine stent procedure.

PMID- 9532935
TI  - [Copper and zinc metabolic derangement in patients with chronic pyelonephritis
      developing nephrosclerosis and renal insufficiency].
AB  - Cu and Zn levels were measured (nuclear-absorption spectrophotometry) in the
      blood and urine from patients with chronic pyelonephritis (CP) in emergence of
      nephrosclerosis and renal insufficiency. CP patients were found to develop
      hypercupremia as early as initial stages of nephrosclerosis when renal
      insufficiency was not apparent. Blood Zn was low, especially in development of
      chronic renal insufficiency. Cu and Zn disbolism may contribute to formation of
      sclerotic lesions in the kidneys and to development of chronic renal
      insufficiency. Assay for Cu and Zn is proposed for early diagnosis of
      nephrosclerosis and provides objective clinical control over the disease course
      to make timely correction of the detected defects and valid prognosis.

PMID- 9532936
TI  - [Role of hepatic monooxygenase activity study in optimization of
      immunosuppressive therapy and optimal use of ketoconazole in patients with
      transplanted kidney].
AB  - The aim of the study is to evaluate the activity of hepatic monooxidase enzymic
      system (MOS) in patients with chronic renal failure before and after
      transplantation of the kidney, to elucidate the relationship between MOS activity
      and clinical features of the disease, to validate effective dose of MOS inhibitor
      ketokonasole. MOS activity was measured by antipirine half-life. By initial MOS
      activity, three groups of oxidizers were recognized: fast, moderate, slow. Native
      population of the North and some ethnic groups prevailed among fast "oxidizers".
      MOS activity measured 2 months after transplantation of the kidney was
      characterized by a spontaneous fall of MOS activity, recovery of renal
      elimination. Fast "oxidizers" demonstrated greater frequency of acute rejection,
      less frequent episodes of cyclosporine nephrotoxicity, higher cumulative dose of
      steroid hormones and weak response to azatioprin. Effective dose of ketokonasole
      was within 100-200 mg/day under the same pharmacodynamic effect. It was found
      reasonable to measure MOS activity for decision about administration of optimal
      immunosuppressive therapy and ketokonasole.

PMID- 9532937
TI  - [Cryogenic effect on renal tissue and condition of intrarenal hemodynamics].
AB  - The paper presents experimental evidence on morphologic changes in intact kidney,
      tissue temperature, renal blood supply and glomerular filtration in response to
      freezing. Cryogenic effects manifested as necrotic and dystrophic processes.
      Damage to the tubular and glomerular cells can be corrected. Blood flow in the
      kidney was not interrupted but was directed through the bypass routes.

PMID- 9532938
TI  - [Effects of shock-wave lithotripsy (ESWL) on electrolytic and hormonal balance in
      nephrolithiasis patients].
AB  - Blood concentrations of parathyroid hormone, aldosterone, hydrocortisone, Na+,
      K+, Ca2+, 24-h urine concentration of Ca2+, blood pressure were measured on day 3
      and 7 after extracorporeal shock-wave lithotripsy. A total of 54 patients with
      nephrolithiasis (NL) were examined. In NL patients with hypertension the above
      lithotripsy led to a fall in pressure by 15-20%, to correction of initial
      hormonal and electrolytic unbalance. There were marked changes in the levels of
      parathyroid hormone, total Ca2+ in the blood and 24-h urine.

PMID- 9532939
TI  - [Dose loads on the patients in extracorporeal shok-wave lithotripsy (ESWL)].
AB  - The method of extracorporeal shock-wave lithotripsy (ESWL) is widely practiced in
      urology as effective and less traumatic. Utilization of x-ray and video control
      during ESWL sessions raises the problem of radiation protection of the patient
      and medical personnel as well as registration of the exposure dose for estimation
      of further permissible doses. The examination covered 48 patients of different
      age suffering from urolithiasis. All of them received ESWL treatment using units
      URAT (Russia) and LITOSTAR (Germany) having x-ray positioning. It was found that
      mean effective dose load for LITOSTAR unit was higher than for URAT unit. The
      larger part of the dose is generated while localizing the stone and focusing.
      URAT is furnished with logements protecting vital organs. This is of particular
      importance for children. ESWL departments with TV x-rat system should meet the
      requirements for jobs with occupational hazards. In multisession lithotripsy
      dynamic monitoring should be performed by ultrasound X-ray examination should be
      employed only in growing dilatation of the renal pelvis, prodromal signs of acute
      pyelonephritis and failure of the effects to eliminate concrements.

PMID- 9532940
TI  - [Early diagnosis of urolithiasis, assessment of its activity and composition of
      lithogenic urine salts (Litos system)].
AB  - Until recently, the diagnosis of urolithiasis has been made by its complication-
      an apparent calculus in the kidney. We have discovered the phenomenon of
      pathological crystallization of urinary lithogenetic salts. Now, basing on this
      phenomenon we are able to make a diagnosis of urolithiasis at its preclinical
      stage, i.e. before the appearance of renal calculus, to control the course of
      urolith formation and to find out composition of the stone. We propose a complex
      of original techniques (Litos system) which provides pathogenetic diagnosis of
      urolithiasis.

PMID- 9532941
TI  - [Blood reinfusion in massive blood loss during urological operations].
AB  - In massive blood loss (1000-4900 ml) during operations on the kidneys, urinary
      tract and prostate in 65 patients 750 to 3600 ml of blood were reinfused. Sixty
      (92.3%) patients recovered. Fatal outcomes in 5 cases were caused by
      complications of the underlying and concomitant diseases and were unrelated to
      blood reinfusion. Study of morphological, biochemical and coagulation properties
      of the patients' blood showed gradual restoration of hemostatic values and the
      absence of harmful effect of the reinfusion on the organism. The authors claim
      that blood reinfusion can be undertaken in operations on the kidney, urinary
      tract and prostate when there are vital indications. Kidney tumors are a relative
      contraindication for reinfusion. Blood reinfusion is not indicated in purulent
      diseases of the kidneys.

PMID- 9532942
TI  - [Preoperative examination of cardiovascular system in elderly and old urological
      patients].

PMID- 9532943
TI  - [Morphological alternations and hemostatic disturbances as manifestation of
      mesenchymal dysplasia in nephroptosis patients].
AB  - The examination of 36 nephroptosis patients (33 females and 3 males, mean age 23
      years) included assessment of hemostasis before and after nephropexia (15
      patients), histological investigation of renal parenchyma biopsies (15 patients)
      and those of the skin from the lateral abdominal surface and musculus lumborum
      fascia (5 patients). Changes characteristic for an early stage of microcystosis
      were found in all the renal tissue biopsies. In the skin and muscular connective
      tissue there were dystrophic changes. Collagen fibers were undergoing elastoid
      degeneration. As to hemostatic disorders, there were diverse platelet
      dysfunctions and/or thrombocytopenias, 9 patients had low plasma level of
      Willebrand's factor, 28 showed impaired terminal clotting. Combination of the
      above defects was registered in 12 of 36 examinees. After nephropexia, platelet
      count and fibrinogen level noticeably increased, hemostatic disorders aggravated.
      Thus, nephroptosis is manifestation of connective tissue pathology associated
      with marked hemostatic changes.

PMID- 9532944
TI  - [Localized and locally advanced renal cell carcinoma: method of outcome
      prognosis].
AB  - Basing on the long-term results of nephrectomy in 180 patients with renal cell
      carcinoma, the detailed assessment has been made of implications of a number of
      factors in 5-year survival and contribution of these factors to the disease
      outcome. The author proposes a method of prognosticating the disease outcome in
      patients with localized and locally advanced renal carcinoma which enables
      specification of the existing international classification and more precise
      prognosis of the disease. At stages T2, T3 and T4, 5-year survival reached in the
      subgroups with good prognosis 74.1, 100, and 30.8% of patients, respectively;
      with poor prognosis 7.1, 5.3, and 0%, respectively. Prognostic subgroup of the
      patient should be considered in the design of the treatment scheme.

PMID- 9532945
TI  - [Optimization of hydrodynamic conditions in transurethral resection of benign
      prostatic hyperplasia].
AB  - Water intoxication remains a serious complication of transurethral resection
      (TUR) occurring more frequently in patients with large-size benign prostatic
      hyperplasia (BPH) and in those who was operated for more than 1 hour. An advanced
      irrigation system employing mechanical valve "Floval" and active aspiration
      provides controlled irrigation of the bladder preventing spontaneous rise of
      intravesical pressure in conducting TUR in BPH patients.

PMID- 9532946
TI  - [Correction of abnormal lipid peroxidation in treatment of chronic prostatitis].
AB  - Lipid peroxidation activity is an essential factor in development of chronic
      inflammation of the prostate when local and general antioxidant defense are
      diminished. This fact says in favor of using antioxidants in the treatment of
      chronic prostatitis. Positive effects of nonenzymic and enzymic bioantioxidants
      (alpha-tocopherol and ceruloplasmin, respectively) were achieved in combination
      with rectal magnetotherapy.

PMID- 9532947
TI  - [Physico-biological aspects of laser radiation in endoscopic surgery of benign
      prostatic hyperplasia].

PMID- 9532948
TI  - [Sacral nerve stimulation in the treatment of urination disorders and pelvic
      pain].

PMID- 9532949
TI  - Time to spring into action against. Seasonal allergies.

PMID- 9532950
TI  - New success against stroke. Prevention, improved therapies help fight this
      devastating condition.

PMID- 9532951
TI  - Keeping an eye on contact lenses. Safety, options shape contact lens decisions.

PMID- 9532952
TI  - Condoms. Barriers to bad news.

PMID- 9532953
TI  - What to do when your back is in pain.

PMID- 9532954
TI  - Alpha hydroxy acids for skin care.

PMID- 9532955
TI  - Court halts company's use of unapproved product from Russia.

PMID- 9532956
TI  - Mail-order Rx drug schemer receives prison sentence.

PMID- 9532957
TI  - Selling drug samples lands doctor in prison.

PMID- 9532958
TI  - Crime is a public health problem.
AB  - Crime is a public health issue. It shares common causes with ill health,
      particularly poverty, and fear of violent crime is itself a major cause of
      anxiety. Community development in pre-school education, parental education, and
      among ethnic minorities, both reduces crime and promotes better health, for
      example in reducing the effects of alcohol and illicit drugs. Health workers
      should contribute in full to community development.

PMID- 9532959
TI  - Human violence: a treatable epidemic.
AB  - Domestic violence is common, afflicting at least one in 15 of the population. The
      victims are usually women and children and the perpetrators often the traditional
      male head of the family. It commonly leads to a form of post-traumatic stress
      disorder manifested as psychiatric illness in women and violent crime in men. It
      is proposed that a major underlying factor is a failure of attachment in infancy.
      This form of violence can be prevented by better health care before and after
      birth, particularly in the inner cities and with reduction of inequality;
      education for parenting; free nursery education; and diminishing 'legitimate'
      violence, in the media, by government (capital or corporal punishment) and as
      violent sporting activities.

PMID- 9532960
TI  - Obligatory "expectations" of expressive timing induced by perception of musical
      structure.
AB  - Previous research has shown that, in a task requiring the detection of local
      deviations from mechanically precise timing in music, the relative detectability
      of deviations in different positions is closely related to the typical expressive
      timing pattern musicians produce when playing the music. This result suggests
      that listeners expect to hear music expressively timed and compensate for the
      absence of expressive timing. Three new detection experiments shed additional
      light on the nature of these timing expectations in musically trained listeners.
      Experiment 1 shows that repeated exposure to an atypically (but not unmusically)
      timed performance leaves listeners' timing expectations unaffected. Experiment 2
      demonstrates that the expectations do not manifest themselves when listeners
      merely imagine the music in synchrony with a click track. Experiment 3, however,
      shows that the timing expectations are fully operational when the click track is
      superimposed on the music. These results reveal timing "expectations" to be an
      obligatory consequence of the ongoing auditory perception of musical structure.

PMID- 9532961
TI  - Perceptual categorization: connectionist modelling and decision rules.
AB  - Although it is currently popular to model human associative learning using
      connectionist networks, the mechanism by which their output activations are
      converted to probabilities of response has received relatively little attention.
      Several possible models of this decision process are considered here, including a
      simple ratio rule, a simple difference rule, their exponential versions, and a
      winner-take-all network. Two categorization experiments that attempt to
      dissociate these models are reported. Analogues of the experiments were presented
      to a single-layer, feed-forward, delta-rule network. Only the exponential ratio
      rule and the winner-take-all architecture, acting on the networks' output
      activations that corresponded to responses available on test, were capable of
      fully predicting the mean response results. In addition, unlike the exponential
      ratio rule, the winner-take-all model has the potential to predict latencies.
      Further studies will be required to determine whether latencies produced under
      more stringent conditions conform to the model's predictions.

PMID- 9532962
TI  - Effects of retention interval on latent inhibition and perceptual learning.
AB  - Repeated, non-reinforced preexposure to a context slowed development of
      conditioned freezing to that context when it was subsequently paired with
      footshock (latent inhibition) and enhanced discriminability of that context from
      a similar context (perceptual learning) whether assessed by a generalization test
      or by explicit discrimination training. Latent inhibition was eliminated by a
      delay between conditioning sessions and test (Experiments 1a and 1b) and reduced
      by a delay between preexposure and conditioning (Experiment 2). However,
      perceptual learning was unaffected by either of these intervals (Experiments 1b
      and 2). These results are discussed in terms their impact on theories that have
      latent inhibition as a possible mechanism of perceptual learning, and on theories
      of latent inhibition that consider the retardation of conditioned responding to
      be the result of an acquisition failure.

PMID- 9532963
TI  - Loss of latent inhibition of contextual conditioning following non-reinforced
      context exposure in rats.
AB  - Three experiments with rats demonstrated that preexposure to an experimental
      environment retarded the level of conditioned freezing observed on a test in that
      environment after it had been paired with mild footshock. Furthermore, Experiment
      1 demonstrated that this latent inhibition effect could be abolished if
      preexposed rats were exposed to a second experimental environment following
      conditioning to the preexposed environment. Experiments 2 and 3 demonstrated that
      this second environment had to be similar, but not identical, to the preexposed
      environment, and that the influence of exposure to the second environment on
      latent inhibition could be abolished by exposure to that environment prior to
      footshock conditioning. These results are considered in terms of the Dickinson
      Burke (1996) theory of retrospective revaluation, and their implications for
      experiments demonstrating a loss of latent inhibition across a delay are
      considered.

PMID- 9532964
TI  - Knowing about people and naming them: can Alzheimer's disease patients do one
      without the other?
AB  - It has recently been suggested that patients with semantic breakdown may show the
      phenomenon of so-called "naming without semantics". If substantiated, this
      finding would clearly have a major impact on theories of face and object
      processing, all of which assume that access to semantic knowledge is a
      prerequisite for successful naming. In order to investigate this issue, we
      studied recognition, identification (the ability to provide accurate
      information), and naming of 50 famous faces by 24 patients with mild to moderate
      dementia of Alzheimer type (DAT) and 30 age-matched controls. The DAT group was
      impaired in all three conditions. An analysis of the concordance between
      identification and naming by each patient, for each stimulus item, established
      that naming a famous face was possible only with semantic knowledge sufficient to
      identify the person. Our data support the hypothesis that naming is not possible
      unless semantic information associated with the target is available. Naming
      without semantics, therefore, did not occur in patients with DAT. By contrast,
      there were 206 instances (17% of the total responses) in which the patients were
      able to provide detailed, accurate identifying information yet were unable to
      name the person represented. The implication of these findings for models of face
      identification and naming are discussed.

PMID- 9532965
TI  - The effects of intermittent illumination on a visual inspection task.
AB  - Two experiments are described in which eye movements were monitored as subjects
      performed a simple target-spotting task under conditions of intermittent
      illumination produced by varying the display-screen frame rate on a computer VDU.
      In Experiment 1, subjects executed a saccade from a fixation point to a target
      which appeared randomly at a fixed eccentricity of 14 character positions to the
      left or right. Saccade latency did not differ reliably as a function of screen
      refresh rate, but average saccade extent at 70 Hz and 110 Hz was reliably shorter
      than at 90 Hz and 100 Hz. Experiment 2 examined the same task using a range of
      target eccentricities (7, 14, and 28 character positions to the left and right)
      and across a wider range of screen refresh rates. The results confirmed the
      curvilinear relationship obtained in Experiment 1, with average saccade extent
      reliably shorter at refresh rates of 50 Hz and 125 Hz than at 75 Hz and 100 Hz.
      While the effect was greater for remote targets, analyses of the proportional
      target error failed to show a reliable interaction between target eccentricity
      and display refresh rate. In contrast to Experiment 1, there was a pronounced
      effect of refresh rate on saccade latency (corrected for time to write the screen
      frame), with shorter latencies at higher refresh rates. It may be concluded that
      pulsation at frequencies above fusion disrupts saccade control. However, the
      curvilinear functional relationship between screen refresh rate and saccade
      extent obtained in these studies differs from previously reported effects of
      intermittent illumination on the average size of "entry saccades" (the first
      saccade to enter a given word) in a task involving word identification (Kennedy &
      Murray, 1993a, 1996). This conflict of data may arise in part because within-word
      adjustments in viewing position, which are typical of normal reading, influence
      measures of average saccade extent.

PMID- 9532966
TI  - Speech perception in children with specific reading difficulties (dyslexia).
AB  - Many experimental studies over the last two decades have suggested that groups of
      children who suffer significant delay in reading also show a weakness in phoneme
      discrimination and identification. In order to look further at the relation
      between type of reading deficit, auditory acuity, and speech discrimination, a
      group of 13 children with specific reading difficulty (SRD), 12 chronological-age
      controls, and 12 reading-age controls were tested on a battery of speech
      perceptual, psychoacoustic, and reading tests. A sub-group of children with
      Specific Reading Difficulty (SRD) were poor at speech discrimination tests,
      whereas the rest of the SRD group performed within norms. For this sub-group,
      discrimination performance was particularly poor for consonant contrasts
      differing in a single feature that was not acoustically salient, and problems
      were encountered with nasal and fricative contrasts as wells with stop contrasts.
      These children did not differ from controls in their performance on non-speech
      psychoacoustic tasks. An evaluation is made of the reported phonemic awareness
      skills of beginning readers with regard to speech-processing issues which may
      help in understanding what factors are important in reading development.

PMID- 9532967
TI  - Interfering with the central executive by means of a random interval repetition
      task.
AB  - Four dual-task experiments are reported in which a short-term memory task is
      performed concurrently with a random interval repetition task, which was designed
      to interfere with functions normally attributed to the central executive in the
      working memory model of Baddeley and Hitch (1974). The task was found to
      interfere with supra-span serial recall and with backward memory span, but did
      not disrupt performance on a forward-memory-span task. The effects were observed
      in dissociation with effects of articulatory suppression and matrix tapping, so
      that the locus of the effects of the new task is not due to the slave systems. In
      addition, single-task random-interval repetition performance was sampled and
      compared to performance in the dual-task conditions of all four experiments.
      Although quality of tapping performance differed between the single-task and the
      dual-task conditions, it was not related to recall performance. All the results
      are discussed with reference to the working memory model.

PMID- 9532968
TI  - Effect of superoxide dismutase on a rabbit model of chronic allergic asthma.
AB  - BACKGROUND: In bronchial asthma, inflammatory cells infiltrating the airway
      mucosa release oxygen radicals that cause tissue damage and amplify the airway
      inflammation. Antioxidant enzymes may have a protective effect on the airways.
      OBJECTIVE: The purpose of this study was to determine whether treatment of a
      rabbit model of chronic allergic asthma with the antioxidant enzyme superoxide
      dismutase conjugated to polyethylene glycol will protect the airways from oxygen
      radical injury, decrease airway inflammation, and attenuate the asthmatic
      response. METHODS: New Zealand white rabbits were sensitized to ragweed. Baseline
      histamine PC30, ragweed PD30, and early and late phase asthmatic response to
      ragweed bronchial challenge were measured. The rabbits were then randomized into
      two groups that received every 48 hours an intravenous dose of either superoxide
      dismutase-polyethylene glycol 10,000 U/kg or inactivated superoxide dismutase
      polyethylene glycol as control, followed by a 1-hour exposure to aerosolized
      ragweed extract. After 4 weeks the rabbits had a second bronchial challenge, were
      sacrificed, and lung histology was studied. RESULTS: On the posttreatment
      challenge, the superoxide dismutase-polyethylene glycol group had a rise in
      ragweed PD30, while the control group had no change in ragweed PD30, and two of
      five rabbits in the superoxide dismutase-polyethylene glycol group did not have
      an early or late phase asthmatic response, while all rabbits in the control group
      had an asthmatic response. There was no significant difference in lung histology
      between both groups. CONCLUSION: A rabbit model of chronic allergic asthma
      treated with superoxide dismutase-polyethylene glycol showed a trend of
      improvement in airway responsiveness but no significant effect on airway
      inflammation.

PMID- 9532969
TI  - Failure of zafirlukast to prevent ibuprofen-induced anaphylaxis.
AB  - BACKGROUND: Anaphylaxis to nonsteroidal anti-inflammatory drugs is thought to
      depend on cycloxygenase inhibition coupled to upregulation of 5-lipoxygenase
      dependent pathways. The introduction of leukotriene-receptor antagonists afforded
      the opportunity to test this hypothesis. These agents provide at least partial
      protection against aspirin-induced anaphylaxis during controlled challenges but
      we did not know whether the level of protection was high enough to block symptoms
      from ingestion of a full dose of aspirin. METHODS: We report a patient with
      moderately severe asthma who experienced an episode of anaphylaxis following
      ingestion of 400 mg of ibuprofen while under therapy with 20 mg of zafirlukast
      given twice a day. RESULTS: No further episodes of anaphylaxis have been noted
      following institution of complete avoidance to all nonsteroidal anti-inflammatory
      drugs. CONCLUSIONS: Patients who are sensitive to cycloxygenase inhibitors should
      practice complete avoidance of these drugs even while under therapy with
      leukotriene modifiers.

PMID- 9532971
TI  - Exercise-induced asthma in children: a comparative study of free and treadmill
      running.
AB  - BACKGROUND: Exercise is one of the most common precipitating factors of acute
      asthmatic crises in childhood. Although it has been described as more frequent
      among children, this is probably due to their more abundant physical activity.
      Nevertheless, it also occurs at other ages. OBJECTIVE: The aim of this study is
      to assess possible differences in postexercise spirometry after treadmill and
      free running provocation tests. METHODS: We compared the results obtained in a
      treadmill test performed by 30 asthmatic children and 30 healthy children with
      the results obtained with these same children in a free running test, keeping
      similar environmental conditions (temperature and humidity), exercise intensity
      (assessed by heart rate), and airway status at the time of the test. RESULTS:
      Seventy-three percent of the patients had positive treadmill tests and 63.3% had
      positive free running tests. For the spirometric parameters studied, there were
      no significant differences in the percent decrease in postexercise performance
      after either of the provocation tests. For FEV1, which is the most sensitive
      diagnostic parameter, the sensitivity was 53.3% in treadmill running and 56.7% in
      free running, with a specificity of 100% in both tests. CONCLUSIONS: If
      environmental conditions, exercise intensity, and airway status are controlled at
      the time of the test, treadmill and free running can be used indistinctly as
      asthma-inducing exercises.

PMID- 9532970
TI  - Sudden infant death syndrome: a search for allergen hypersensitivity.
AB  - BACKGROUND: Sudden infant death syndrome (SIDS) remains a diagnosis by exclusion
      which leaves few if any pathologic clues to its etiology. Previous evaluations
      for anaphylaxis in SIDS have been few and limited. OBJECTIVE: To analyze forensic
      blood specimens for evidence of anaphylaxis in 51 (43 boys and 8 girls) children
      dying of SIDS and 13 (9 boys and 4 girls) age-matched controls who died from
      defined, nonanaphylactic causes. METHODS: Specimens collected over a 5-year
      period were assayed for (1) total IgE (IU/mL) by immunoenzymatic assay; (2)
      latex, cat, dust mite (Dermatophagoides farinae and Dermatophagoides
      pteronyssinus), milk, soy, wheat, peanuts, egg, and tomato specific-IgE by RAST;
      and (3) serum tryptase levels (U/L) by radioimmunoassay. RESULTS: The 51 SIDS
      cases (median age 3 months; range 1 to 9 months) and 13 control cases (median age
      4 months; range 1 to 11 months) demonstrated similar total IgE of 9.8 +/- 1.1
      IU/mL (mean +/- SEM) and 10.9 +/- 2.8 IU/mL (P = .59). The frequency of
      detectable (> 0.5 U/L) serum tryptase levels among SIDS cases (10/51) was similar
      to controls (3/13, P = .72). The frequency of positive RAST tests was 39% (20/51)
      in SIDS and 38% (5/13) in control subjects (P = .99). Differences in frequencies
      of positive RAST tests in SIDS and control cases were not statistically
      significant for any allergen tested. The most frequently detected allergen
      specific IgE, to milk, was similar in SIDS (22%) and controls (31%, P = .48).
      CONCLUSIONS: Elevated tryptase levels and allergen-specific IgE (milk, soy,
      wheat, peanuts, egg, tomato, dust mites, cat, and latex) were demonstrated in
      some infant SIDS deaths but were no more common than in controls. We conclude
      that anaphylaxis is probably an uncommon etiology for SIDS.

PMID- 9532972
TI  - Prevalence of atopy in students from Malaga, Spain.
AB  - BACKGROUND: Epidemiologic studies are necessary to determine the prevalence of
      allergic diseases. This varies widely depending on allergen preparations and
      patients studied. OBJECTIVE: To investigate the prevalence of atopic disease,
      skin test reactivity, total and specific IgE to common allergens, and other
      variables in a sample of students from Malaga, southern Spain. METHODS: Three
      hundred sixty-five students (age 17.9 +/- 1.18) were interviewed by an allergist.
      Skin prick tests were performed with Dermatophagoides pteronyssinus, Artemisia
      vulgaris, Plantago lanceolata, Chenopodium album, Olea europaea, Phleum pratense,
      Parietaria judaica, Cynodon dactylon, Alternaria tenuis, and cat dander. Total
      and specific IgE to D. pteronyssinus, Olea, and Parietaria were determined.
      RESULTS: Of all subjects studied, 19.9% suffered from rhinoconjunctivitis, 4.1%
      rhinoconjunctivitis plus asthma, 3.1% asthma alone, and 0.8% atopic dermatitis;
      46.4% had a positive skin test to at least one allergen (28.2% to D.
      pteronyssinus, 20.4% to Olea, 13.8% to Phleum); and 43% had total IgE > 100 kU/L
      and 44.7% a family history of atopy. Allergic symptoms were strongly associated
      with skin test positivities and family allergic history. Patients with asthma or
      skin prick test positive had higher total IgE values than others (P < .01). There
      was a significant correlation between specific IgE values and wheal size in skin
      test. CONCLUSIONS: Our findings confirm the high prevalence of atopic diseases,
      and the close relationship of skin tests reactivity (or presence of specific IgE)
      to allergens with symptoms of asthma and rhinitis. The presence of a family
      history of allergic diseases influences the development of positive skin tests
      and atopic illness. Dermatophagoides pteronyssinus and pollen of Olea europaea
      were found to be the most common allergens.

PMID- 9532973
TI  - Effect of synthetase inhibitors and receptor antagonists in antigen-induced
      contraction of human lung parenchyma.
AB  - BACKGROUND: Chemical mediators induce bronchoconstriction, enhance vascular
      permeability, and promote inflammation. The use of synthetase inhibitors and
      receptor antagonists of these mediators may be useful in the treatment of asthma.
      OBJECTIVES: We evaluated the role of chemical mediators in mite antigen-induced
      contraction in resected human lung parenchyma using synthetase inhibitors and
      receptor antagonists for these mediators. METHODS: Resected human lung
      parenchymal specimens were passively sensitized with serum obtained from patients
      with asthma showing an IgE RAST score for mites > or = 5. The specimens were
      suspended in Magnus bath filled with buffer. After confirmation of contraction
      using PGF2 alpha, buffer or synthetase inhibitors or receptor antagonists of
      various chemical mediators were added. Contraction of parenchyma was induced by
      the addition of mite antigen, and the concentration of thromboxaneB2 (TXB2),
      leukotriene (LT), and histamine was measured before and after contraction.
      RESULTS: Thromboxane A2 (TXA2) synthetase inhibitors significantly inhibited TXB2
      release but not contraction. Leukotriene synthetase inhibitors significantly
      inhibited both LT release and contraction. The magnitude of the inhibitory effect
      was in the order of LT receptor antagonist > 5-lipoxygenase inhibitor > TXA2
      receptor antagonist > PAF antagonist, TXA2 synthetase inhibitor, antihistamine >
      cyclooxygenase inhibitor. CONCLUSION: Among chemical mediators, LT appears to be
      the most closely involved in the immediate antigen-induced contractile response
      in resected human lung parenchyma. Receptor antagonists produced a more marked
      inhibition of antigen-induced contraction than synthetase inhibitors.

PMID- 9532974
TI  - Latex allergy in operating room nurses.
AB  - OBJECTIVE: To determine the prevalence of allergy to natural rubber latex and
      potential crossreacting foods in operating room nurses. METHOD: Two hundred forty
      seven operating room nurses completed a latex allergy questionnaire. They were
      questioned about symptoms of latex reactivity and about other allergies
      particularly to foods that may crossreact with latex. Informed consent was
      obtained and skin prick testing was performed with natural rubber latex and five
      latex extracts representing low (0.08 to 0.25 microgram/mL) and high (18 to 106
      micrograms/mL) natural rubber latex protein gloves. Skin prick tests were done
      with four potentially crossreacting foods (banana, avocado, kiwi, and potato),
      saline, and histamine controls. RESULTS: One hundred thirty-five (54.7%) nurses
      described allergic symptoms they attributed to latex exposure. Of these 12 (4.9%)
      tested positive to latex extracts alone, 12 (4.9%) tested positive to food
      extracts alone, and 5 (2.0%) tested positive to both latex and crossreactive
      foods. Three of the 17 (17.6%) nurses testing positive to latex gave no history
      of reactivity to latex. Indirect latex ELISA was done on the serum of skin test
      positive patients with a 70.6% sensitivity. CONCLUSION: Of the nurses tested,
      6.9% had positive skin prick tests to latex extracts; 17.6% of these were
      asymptomatic and 29.4% had associated food positive skin prick tests.

PMID- 9532975
TI  - Enhanced neutrophil chemotactic activity after bronchial challenge in subjects
      with grain dust-induced asthma.
AB  - BACKGROUND: There have been few reports suggesting involvement of neutrophils in
      induction of bronchoconstriction after inhalation of grain dust. OBJECTIVES: To
      understand the role of neutrophils in pathogenesis of grain dust-induced asthma.
      MATERIALS AND METHODS: We observed serum neutrophil chemotactic activity during
      grain dust-bronchoprovocation tests in six asthmatic subjects with positive
      bronchial challenges (group I). They were compared with those of six symptomatic
      subjects from the same workplace with negative bronchial challenges (group II).
      RESULTS: After grain dust inhalation, serum neutrophil chemotactic activity
      significantly increased at 30 minutes (P = .028), and then decreased to baseline
      level at 240 minutes (P = .028) in five subjects of group I having isolated early
      asthmatic responses. Enhanced neutrophil chemotactic activity was persistent for
      up to 240 minutes in one asthmatic subject having both early and late asthmatic
      responses. There was, however, no significant change in serum neutrophil
      chemotactic activity during bronchial challenges in subjects of group II. Pre
      incubation of sera with anti-interleukin-8 (IL-8) antibody did not affect the
      neutrophil chemotactic activity results of group I subjects. CONCLUSION: These
      results suggest that enhanced neutrophil chemotactic activity distinct from IL-8
      may contribute to significant bronchoconstriction induced by grain dust.

PMID- 9532976
TI  - Long-term therapy with recombinant interferon-gamma (rIFN-gamma) for atopic
      dermatitis.
AB  - BACKGROUND: Interferon-gamma (IFN-gamma) is a potent cytokine that modulates IL-4
      induced immune responses. Atopic dermatitis is associated with increased IgE
      levels and decreased IFN-gamma production. Recent phase I and phase II studies
      have suggested that short-term rIFN-gamma therapy is effective in the treatment
      of severe atopic dermatitis. OBJECTIVE: We evaluated the safety and efficacy of
      long-term use of rIFN-gamma for severe atopic dermatitis. METHODS: Fifteen
      patients were treated for a minimum of 22 months with 50 micrograms/m2 rIFN-gamma
      qd or qod. Patients were monitored every 3 months for safety, efficacy, and
      linear growth in pediatric patients. RESULTS: Data represented a total of 47
      patient years, which included 29 pediatric patient years. There was a
      statistically significant decrease in mean total body surface area involvement
      over time (P < .001, ANOVA). Mean total body surface area involvement was 61.6%
      at baseline and decreased to 18.5% at 24 months (P < .001). Likewise, there was a
      statistically significant decrease in the clinical severity parameters. The mean
      total clinical severity score was 11.4 at baseline and decreased to 6.3 at 24
      months (P < .001). Statistically significant decreases in WBC, neutrophil counts,
      and eosinophil counts were observed compared with baseline counts. No other
      significant laboratory abnormalities or growth problems were seen. CONCLUSIONS:
      We conclude that rIFN-gamma appears to be a safe long-term therapy for patients
      with severe atopic dermatitis.

PMID- 9532977
TI  - Allergic and immunologic profile of symptomatic Persian Gulf War veterans.
AB  - BACKGROUND: Persian Gulf War veterans have been enrolled in the Veterans
      Administration Persian Gulf Health Registry for evaluation of unexplained
      symptoms and illnesses. The allergy and immunology division at the West Los
      Angeles Veterans Administration Medical Center evaluated 20 consecutive
      symptomatic Persian Gulf War veterans. OBJECTIVE: The purpose of this study was
      to examine the immunologic profiles of symptomatic Persian Gulf War Veterans.
      METHODS: A detailed history was obtained that included duties/responsibilities,
      length of time in the Persian Gulf, location, and exposures during the Gulf War.
      A complete physical examination was performed, with extensive laboratory testing
      and immediate and delayed hypersensitivity skin testing. Data from these Persian
      Gulf War Veterans were compared with a control population consisting of 44 non
      Persian Gulf War veterans enrolled in our allergy and immunology clinic.
      Presenting allergic symptoms, presence of atopy, and total serum IgE levels were
      compared. RESULTS: Persian Gulf study patients and registry patients had a broad
      spectrum of nonspecific symptoms as compared with allergy clinic control patients
      who had dermatologic and respiratory symptoms. Persian Gulf study patients with
      allergy symptoms had a higher mean IgE level (88.7 IU/mL) than Persian Gulf study
      patients without allergy symptoms (47.5 IU/mL). Persian Gulf study patients with
      positive skin tests had a higher mean IgE level (161.5 IU/mL) than Persian Gulf
      study patients with negative skin tests (22.3 IU/mL). Laboratory data showed no
      significant immune abnormalities. CONCLUSION: Our study showed that 20 Persian
      Gulf veterans with a multitude of nonspecific symptoms had no immune abnormality.
      Mean IgE levels and eosinophil counts correlated with atopic state and reported
      allergy symptoms.

PMID- 9532978
TI  - Highly sensitive and specific ELISA with monoclonal antibody capture to measure
      Dermatophagoides farinae 1-specific IgE.
AB  - BACKGROUND: Dermatophagoides farinae (Der f) is a major allergen in Der f
      extract. Measurement of Der f I-specific IgE has not been commonly used, because
      of the difficulty in obtaining large amounts of purified Der f 1. OBJECTIVES: To
      improve the diagnosis of dust mite allergy, we wanted to develop an ELISA to
      measure Der f 1-specific IgE in which purified Der f 1 is not required. METHODS:
      Using a monoclonal antibody (mAb) against Der f 1, a mAb-capture ELISA was
      developed. Microplates coated with the mAb were sequentially incubated with crude
      Der f extract, serum samples, goat anti-human IgE, and conjugated rabbit anti
      goat IgG. A conventional ELISA using purified Der f 1 as capture (Der f 1-ELISA)
      was developed to compare it with the mAb-capture ELISA. RESULTS: There was a
      significant correlation between the two ELISAs (r = 0.89, P < .001) with a
      sensitivity of 0.8 U/mL. Both the assays were inhibited by the crude Der f
      extract in a dose-dependent manner. Using the two ELISAs, serum Der f 1-specific
      IgE was evaluated in 12 allergic patients with positive skin tests to Der f
      extract, 14 allergic patients with negative skin tests to Der f extract, and 15
      healthy subjects. The mean Der f 1-IgE and the positivity rate of Der f I-IgE
      were higher in the mite-allergic group and lower in the healthy group when the
      mAb-ELISA was used (P < .01) than when the Der f 1-ELISA was used (P < .05).
      CONCLUSIONS: Der f 1-specific IgE can be measured by mAb-capture ELISA using
      crude Der f extract. The mAb-ELISA is more sensitive and specific than the
      conventional Der f 1-capture ELISA in diagnosing dust mite allergy.

PMID- 9532979
TI  - Pollen and fungal spores indoor and outdoor of mobile homes.
AB  - BACKGROUND: Allergenic diseases triggered by aeroallergens extract a health cost
      in quality of life and in economic impact. People generally spend 90% to 95% of
      their time indoors, so understanding the environmental factors that affect the
      presence of aeroallergens indoors are important in understanding health impact
      and potential intervention methods. OBJECTIVE: Describe the relationship of
      indoor airborne pollen and fungal spores in occupied mobile homes with outdoor
      concentrations and other environmental factors within geographically diverse
      areas of Texas. METHODS: Airborne pollen and fungal spores were collected during
      the daytime with RotoRod samplers indoor and outdoor of mobile homes in Houston
      and El Paso, Texas. Samples were counted simultaneously with a dual eyepiece
      microscope and identified morphologically and through staining techniques.
      RESULTS: Geometric mean concentrations (counts/m3) indoors and outdoors for
      pollen, respectively, were Houston 7.1 and 196.4; and El Paso 17.5 and 71.5.
      Geometric mean concentrations (counts/m3) indoors and outdoors for spore,
      respectively, were Houston 98.5 and 196.4; and El Paso 36.9 and 71.5. Indoor to
      outdoor ratios (I/O) for pollen and fungal spores were found to be higher on
      average than has been previously reported. Modeling of predictive factors in
      Houston demonstrate that 62% and 41% of indoor levels of pollen and fungal
      spores, respectively, can be explained by their corresponding outdoor levels.
      These data suggest that the many factors associated with individual exposure to
      airborne pollen and fungal spores indoors are under the control of the occupant,
      and may additionally be influenced by the physical characteristics of mobile
      homes, in particular the high surface area to volume ratio and restricted flow
      patterns.

PMID- 9532980
TI  - Genetic testing for cystic fibrosis.
AB  - OBJECTIVE: To provide health care providers, patients, and the general public
      with a responsible assessment of the optimal practices for genetic testing for
      cystic fibrosis (CF). PARTICIPANTS: A non-Federal, nonadvocate, 14-member panel
      representing the fields of genetics, obstetrics, internal medicine, nursing,
      social work, epidemiology, pediatrics, psychiatry, genetic counseling, bioethics,
      health economics, health services research, law, and the public. In addition, 21
      experts from these same fields presented data to the panel and a conference
      audience of 500. EVIDENCE: The literature was searched through Medline, and an
      extensive bibliography of references was provided to the panel and the conference
      audience. Experts prepared abstracts with relevant citations from the literature.
      Scientific evidence was given precedence over clinical anecdotal experience.
      CONSENSUS PROCESS: The panel, answering predefined questions, developed its
      conclusions based on the scientific evidence presented in open forum and the
      scientific literature. The panel composed a draft statement that was read in its
      entirety and circulated to the experts and the audience for comment. Thereafter,
      the panel resolved conflicting recommendations and released a revised statement
      at the end of the conference. The panel finalized the revisions within a few
      weeks after the conference.

PMID- 9532981
TI  - We should routinely offer HIV screening in pregnancy. Pregnancy Subgroup of the
      Herpes Simplex Advisory Panel.

PMID- 9532982
TI  - Could ovarian infection impair ovarian response to gonadotrophin stimulation?

PMID- 9532983
TI  - The management of herpes simplex virus infection in pregnancy.

PMID- 9532984
TI  - Magnesium sulphate: a review of clinical pharmacology applied to obstetrics.

PMID- 9532985
TI  - Mandatory prenatal screening for the human immunodeficiency virus: the experience
      in south-eastern France of a national policy, 1992-1994.
AB  - OBJECTIVE: To evaluate the impact of the 1993 French National Policy which made
      it mandatory to offer screening for the presence of human immunodeficiency virus
      (HIV) to all pregnant women who planned to give birth, although women remained
      free to refuse the test. DESIGN: Successive surveys in April 1992 and May 1994 in
      south-eastern France. Logistic regressions were performed to identify factors
      which affected access to HIV testing for women who gave birth and those who
      terminated their pregnancy, and for each year of study. MAIN OUTCOME MEASURES:
      Attitudes and access to HIV testing among pregnant women, irrespective of
      pregnancy outcome. SETTING: All obstetrics and gynaecology departments and
      abortion clinics in the region. POPULATION: 3497 women in 1992 (2775 who were
      delivered and 722 who chose termination) and 3407 in 1994 (2701 who were
      delivered and 766 who chose termination). The response rates were 82% and 88%,
      respectively. RESULTS: In 1994 of women who were delivered, 73% had an HIV test,
      compared with 63% in 1992 (P < 0.001); however of women who terminated their
      pregnancy, only 28% had an HIV test, compared with 24.5% in 1992 (P not
      significant), although they were more at risk for HIV infection. Socioeconomic
      differences affecting access to testing were reduced between 1992 and 1994, but
      only among women who gave birth. CONCLUSION: Introduction of a policy which makes
      it mandatory to offer HIV screening to all women who intended to have their baby
      improved access to screening but did not improve the rate of preventative
      counselling. A mandatory requirement to offer HIV screening should be extended to
      women who request termination of pregnancy.

PMID- 9532986
TI  - A randomised placebo controlled trial of suppressive acyclovir in late pregnancy
      in women with recurrent genital herpes infection.
AB  - OBJECTIVE: To evaluate the efficacy and safety of a suppressive course of
      acyclovir in late pregnancy in women with recurrent genital herpes infection on
      the incidence of viral shedding, herpes lesion development and caesarean section
      for recurrent genital herpes. DESIGN: Double-blind, randomised placebo controlled
      clinical trial. SETTING: A department of genitourinary medicine in Sheffield and
      an antenatal clinic in London. POPULATION: Pregnant women with recurrent genital
      herpes infection at < 36 weeks of gestation. METHODS: Participating women were
      given acyclovir 200 mg four times a day (or matching placebo) from 36 weeks of
      gestation until the time of delivery. Women were seen weekly and viral cultures
      were obtained from the cervix and vulva. Decisions regarding mode of delivery
      were left to the discretion of the attending obstetrician. MAIN OUTCOME MEASURES:
      Delivery by caesarean section for recurrent genital herpes infection. Number of
      episodes of recurrent genital herpes infection and number of episodes of
      asymptomatic viral shedding during the treatment period. In addition blood was
      taken at two weekly intervals to determine acyclovir levels. RESULTS: The total
      number of women recruited was 63 (31 received acyclovir and 32 received placebo).
      The number of women undergoing delivery by caesarean section for recurrent herpes
      at the time of delivery was 12 (19%). The odds ratio for delivery by caesarean
      section in women taking acyclovir, compared with those taking placebo, was 0.44
      (95% CI 0.09-1.59). The odds ratio for clinical recurrences during treatment was
      0.10 (95% confidence interval 0.00-0.86) and the odds ratio for clinical
      recurrence or asymptomatic shedding during treatment was 0.32 (95% CI 0.05-1.56).
      CONCLUSION: This trial was unable to demonstrate that acyclovir can significantly
      decrease the number of caesarean section deliveries; however, the number of
      clinical recurrences was significantly reduced. Two episodes of asymptomatic
      virus shedding both occurred in women taking acyclovir. At the present time there
      is little evidence to suggest that acyclovir should be used outside randomised
      controlled trials for the suppression of recurrent genital herpes infection
      during pregnancy.

PMID- 9532987
TI  - A randomised trial of mode of delivery in women infected with the human
      immunodeficiency virus.
AB  - OBJECTIVE: During the pilot phase of a trial to evaluate the effectiveness of
      caesarean section delivery compared with vaginal delivery in reducing mother-to
      child transmission of human immunodeficiency virus (HIV) infection, the
      feasibility of randomisation to mode of delivery was assessed. DESIGN: At 36
      weeks of pregnancy, women infected with HIV were randomly allocated to either
      caesarean section delivery at 38 weeks or vaginal delivery. Information was also
      collected on the reasons why women were not enrolled, either because they refused
      or had a contraindication. SETTING: Fifty-one centres in six European countries.
      POPULATION: Pregnant women with confirmed HIV-1 infection. MAIN OUTCOME MEASURES:
      Randomisation. RESULTS: Three-hundred and thirty-nine women had been randomised
      by the end of 1996, the large majority from Italy (n = 250) and France (n = 54),
      with 22 from South Africa, three from Sweden, nine from Barcelona and one from
      London. A further 150 women were eligible but had not been randomised. Forty
      eight women (14%) were not delivered according to the arm to which they were
      randomised; the majority (n = 44) were changed from vaginal to caesarean section
      delivery. There is wide variation between European countries in the acceptability
      and adherence to the mode of delivery trial. CONCLUSION: The pilot phase of this
      trial has shown that in some settings randomisation to mode of delivery is
      feasible and acceptable, but that in other settings clinicians and pregnant women
      are more reluctant to be randomised. Pending further information on transmission
      rates and accrual, enrollment into the trial continues.

PMID- 9532988
TI  - Barbados Low Dose Aspirin Study in Pregnancy (BLASP): a randomised trial for the
      prevention of pre-eclampsia and its complications.
AB  - OBJECTIVE: To determine whether prophylactic, low dose controlled-release aspirin
      improves outcome for pregnant women and their babies in Barbados. DESIGN:
      Randomised placebo-controlled trial. SETTING: The Queen Elizabeth Hospital,
      Barbados. POPULATION: All women attending antenatal clinics between 12 and 32
      weeks of gestation were eligible, if without specific contraindications to
      aspirin and unlikely to deliver immediately. METHODS: Randomisation was computer
      generated in the antenatal clinic; 1822 women were allocated to receive 75 mg
      controlled-release aspirin and 1825 matching placebo. MAIN OUTCOME MEASURES:
      Proteinuric pre-eclampsia, other pregnancy-induced hypertension, pregnancy
      duration, birthweight, stillbirths and neonatal deaths, major neonatal events.
      RESULTS: All but three women from each group were followed up successfully. Forty
      four percent were primigravid, and 8% had previous obstetric complications. There
      were no significant differences between the allocated treatment groups in the
      incidence of proteinuric pre-eclampsia (40 [2.2%] of those allocated aspirin,
      compared with 46 [2.5%] allocated placebo), of preterm delivery (255 [14.0%] vs
      270 [14.8%]), of birthweight < 1500 g (32 [1.7%] vs 33 [1.8%]) or of stillbirth
      and neonatal death (44 [2.4%] vs 38 [2.1%]). Aspirin was not associated with
      excess risk of maternal or fetal bleeding. CONCLUSIONS: The results of this study
      in Barbados do not support the routine use of low dose aspirin for prevention of
      pre-eclampsia or its complications, confirming results of previous large trials
      in other settings.

PMID- 9532989
TI  - A randomised trial of low dose aspirin for primiparae in pregnancy. The Jamaica
      Low Dose Aspirin Study Group.
AB  - OBJECTIVE: To investigate whether low dose aspirin medication given to
      primiparous women provides benefit in preventing pre-eclampsia or intrauterine
      growth retardation. DESIGN: Randomised double-blind controlled trial of low dose
      aspirin and placebo in pregnancy. POPULATION: Residents of the parishes of
      Kingston and St Andrew, Jamaica; 6275 primiparae enrolled between 12 and 32 weeks
      of gestation. MAIN OUTCOME MEASURES: Hypertensive disorders of pregnancy
      (including pre-eclampsia and eclampsia), preterm delivery, and low birthweight.
      In addition, to assess whether enrollment early, rather than late had more
      beneficial effect. Possible adverse effects on the woman and her infant were
      monitored. RESULTS: Of enrolled primiparae, 97% were followed throughout
      pregnancy. There were no differences between those on aspirin and those on
      placebo in the development of hypertensive disorders (e.g. for a rise in
      diastolic pressure of 25 mmHg the odds ratio [OR] was 1.02 [95% CI 0.86-1.21];
      for proteinuric pre-eclampsia OR 1.15 [95% CI 0.92-1.44]; eclampsia OR 0.82 [95%
      CI 0.44-1.53]); except for oedema which was significantly less prevalent in those
      on aspirin (OR 0.85 [95% CI 0.75-0.96]). Women on aspirin were no significantly
      less likely to deliver preterm (OR 0.93 [95% CI 0.79-1.09]) or have a larger
      fetus (mean birthweight difference 18 g [95% CI -9 to 45]). They were, however,
      significantly more likely to suffer from bleeding disorders antenatally,
      intrapartum and postpartum; for postpartum haemorrhage OR 1.40 (95% CI 1.13
      1.73). CONCLUSIONS: This trial shows that low dose aspirin has no consistent
      beneficial effect in primiparae.

PMID- 9532990
TI  - A randomised controlled trial of intravenous magnesium sulphate versus placebo in
      the management of women with severe pre-eclampsia.
AB  - OBJECTIVE: To determine whether the administration of prophylactic intravenous
      magnesium sulphate reduces the occurrence of eclampsia in women with severe pre
      eclampsia. DESIGN: Randomised controlled trial. SETTING: A tertiary referral
      obstetric unit. POPULATION: Eight hundred and twenty-two women with severe pre
      eclampsia requiring termination of pregnancy by induction of labour or caesarean
      section. METHODS: The women were randomised to receive either placebo (saline) or
      magnesium sulphate intravenously. The investigators were blinded to the contents
      of the pre-mixed solutions. MAIN OUTCOME MEASURE: The occurrence of eclampsia in
      the two groups. RESULTS: The data of 699 women were evaluated. Fourteen were
      withdrawn after randomisation. The overall incidence of eclampsia was 1.8%. Of
      345 women who received magnesium sulphate, one developed eclampsia (0.3%); in the
      placebo group, 11/340 women (3.2%) developed eclampsia (relative risk 0.09; 95%
      confidence interval 0.01-0.69; P = 0.003). CONCLUSION: The use of intravenous
      magnesium sulphate in the management of women with severe pre-eclampsia
      significantly reduced the development of eclampsia.

PMID- 9532991
TI  - The Collaborative Randomised Amnioinfusion for Meconium Project (CRAMP): 1. South
      Africa.
AB  - OBJECTIVE: To evaluate transcervical amnioinfusion for meconium stained amniotic
      fluid during labout. DESIGN: Multicentre randomised controlled trial. SETTING:
      Four urban academic hospitals in South Africa. Obstetric surveillance included
      the use of electronic fetal heart rate monitoring in most cases. PARTICIPANTS:
      Women in labour at term with moderate or thick meconium staining of the amniotic
      fluid. INTERVENTIONS: Transcervical amnioinfusion of 800 mL saline at 15 mL per
      minute, followed by a maintenance infusion at 3 mL per minute. The control group
      received routine care. Blinding of the intervention was not possible. MAIN
      OUTCOME MEASURES: Caesarean section, meconium aspiration syndrome and perinatal
      mortality. RESULTS: Caesarean section rates were similar (amnioinfusion group
      70/167 vs control group 68/159; RR 0.98, 95% CI 0.76-1.26). The incidence of
      meconium aspiration syndrome was lower than expected on the basis of previous
      studies (4/162 vs 6/163; RR 0.67, 95% CI 0.19-2.33). There were no perinatal
      deaths. There were no significant differences between any of the subsidiary
      outcomes. CONCLUSIONS: This study concurred with three previous trials which
      found no effect of amnioinfusion for meconium-stained amniotic fluid on caesarean
      section rate, though the pooled data from all identified trials to date show a
      significant reduction. The findings with respect to meconium aspiration syndrome
      were inconclusive in this study alone because of the small number of babies
      affected, but the point estimate of the relative risk was consistent with the
      finding of a significant reduction in previous studies and with the Zimbabwe arm
      (CRAMP 2) of this study. Pooled data clearly support the use of amnioinfusion for
      meconium stained amniotic fluid to reduce the incidence of meconium aspiration
      syndrome.

PMID- 9532993
TI  - Pregnancy in women with von Willebrand's disease or factor XI deficiency.
AB  - OBJECTIVE: To assess the obstetric outcome in women with von Willebrand's disease
      or factor XI deficiency. SETTING: Haemophilia Centre and Haemostasis Unit, The
      Royal Free Hospital. POPULATION: Women with von Willebrand's disease (n = 31) and
      with factor XI deficiency (n = 11) registered at the Royal Free Hospital
      Haemophilia Centre who had had a pregnancy within the previous 17 years (1980
      1996), including 84 in women with von Willebrand's disease and 28 in women with
      factor XI deficiency. METHODS: Women were interviewed and details of the
      obstetric history were obtained. The records of the Haemophilia Centre and the
      women's maternity records were also reviewed. RESULTS: Threatened miscarriage
      occurred in 33% and 14% of pregnancies with von Willebrand's disease and factor
      XI deficiency, respectively. Excluding recurrent miscarriages, 14/68 (21%) of
      pregnancies with von Willebrand's disease and one pregnancy with factor XI
      deficiency miscarried spontaneously. There was an increased incidence of primary
      and secondary post-abortal bleeding complications. Factor VIII and von Willebrand
      factor antigen and activity levels increased significantly in pregnancy in all
      women apart from those with severe von Willebrand's disease. Factor XI, however,
      did not show any significant change. No neonatal haemorrhagic complications in
      association with the birth process were reported, although ventouse and difficult
      forceps deliveries were avoided. Extensive perineal bruising and haematoma was
      reported in three women with von Willebrand's disease; two of these were
      associated with forceps delivery. The incidence of primary postpartum haemorrhage
      was 18.5% in von Willebrand's disease and 16% in factor XI deficiency. Blood
      transfusion was required in six cases of von Willebrand's disease and two cases
      of factor XI deficiency. Ten of fourteen instances of primary postpartum
      haemorrhage occurred when maternal factor levels were < 50 IU/dL with no
      prophylactic treatment for labour. The incidence of secondary postpartum
      haemorrhage was 20% in von Willebrand's disease and 24% in factor XI deficiency.
      None of the women who had prophylactic treatment during labour or the puerperium
      suffered any significant bleeding complications. There were three neonatal
      bleeding complications. CONCLUSION: Pregnancy, labour and the puerperium are
      associated with significant bleeding problems in women with von Willebrand's
      disease or factor XI deficiency, but these are largely preventable. Specialist
      obstetric care in close liaison with the haemophilia centre is essential to
      minimise maternal and neonatal complications.

PMID- 9532992
TI  - The Collaborative Randomised Amnioinfusion for Meconium Project (CRAMP): 2.
      Zimbabwe.
AB  - OBJECTIVE: To evaluate transcervical amnioinfusion for meconium stained amniotic
      fluid during labour. DESIGN: Multicentre randomised controlled trial. SETTING: A
      large urban academic hospital. Electronic fetal heart rate monitoring was not
      used. PARTICIPANTS: Women in labour at term with moderate or thick meconium
      staining of the amniotic fluid. INTERVENTIONS: Transcervical amnioinfusion of 500
      mL saline over 30 minutes, then 500 mL at 30 drops per minute. The control group
      received routine care. Blinding of the intervention was not possible. MAIN
      OUTCOME MEASURES: Caesarean section, meconium aspiration syndrome and perinatal
      mortality. RESULTS: There was no difference in risk for caesarean section in the
      two groups (amnioinfusion 9.5% vs control 12.3%; RR 0.84, 95% CI 0.53-1.32).
      Meconium aspiration syndrome was significantly less frequent in the amnioinfusion
      group (3.1% vs 12.8%; RR 0.24, 95% CI 0.12-0.48), and there was a trend towards
      fewer perinatal deaths (1.2% vs 3.6%; RR 0.34, 95% CI 0.11-1.06). CONCLUSIONS:
      Amnioinfusion is technically feasible in a developing country situation with
      limited intrapartum facilities. In this study amnioinfusion for meconium stained
      amniotic fluid was associated with striking improvements in perinatal outcome.

PMID- 9532994
TI  - A population based case-control teratologic study of oral metronidazole treatment
      during pregnancy.
AB  - OBJECTIVE: To study human teratogenic risk of metronidazole. DESIGN: A case
      control analysis of congenital abnormalities after oral metronidazole treatment
      during pregnancy grouped by months of gestation. The source of information
      concerning the use of drugs during pregnancy was the prospective data of the
      women's prenatal logbook and the retrospective data of a questionnaire filled in
      by mothers. SETTING: The large population-based dataset of the Hungarian Case
      Control Surveillance of Congenital Abnormalities, 1980-1991. PARTICIPANTS: The
      control group involved 30,663 pregnant women who had healthy babies; the response
      rate was 65%. The index group consisted of 17,300 pregnant women who had
      offspring with congenital abnormalities from the study pregnancy; data were
      available for 82% of these women. RESULTS: Of 30,663 pregnant women in the
      control group, 1041 (3.4%) were treated with metronidazole, 162 (0.53%) in the
      second to third month of gestation. Of 17,300 pregnant women in the index group,
      665 (3.8%) were treated with metronidazole, 104 (0.66%) in the second to third
      months. McNemar analysis for case-matched control pairs indicated a somewhat
      higher maternal metronidazole treatment in the second-third months of gestation
      in nine cases with cleft lip with or without cleft palate, but it was not
      possible to exclude the recall bias. In addition, this finding was not confirmed
      by the comparison of cases with cleft lip with or without cleft palate and the
      total control group. CONCLUSION: Treatment with oral metronidazole during
      pregnancy presents no clinically important association with congenital
      abnormalities.

PMID- 9532995
TI  - Increase in incidence of gastroschisis in the south west of England in 1995.
AB  - OBJECTIVE: To describe the incidence of gastroschisis and to identify possible
      aetiological factors. DESIGN: A retrospective case review study. SETTING: The
      South West Region of England. POPULATION: All known cases of gastroschisis were
      identified from the regional fetal medicine, ultrasound, pathology and neonatal
      surgery, databases. Datasets to be collected were agreed prospectively and
      included demographic, past medical, family and obstetric information for all
      pregnancies conceived between January 1987 and December 1995. RESULTS: In the
      first eight years the incidence was 1.6/10,000 but in 1995 a highly statistically
      significant rise to 4.4/10,000 was found (P = 0.0009). The increased incidence
      was not associated with changes in maternal age, proportion of primigravidae, use
      of tobacco or illicit drugs, conception while taking the oral contraceptive pill,
      or an increase in the number of teenage pregnancies. The median maternal age at
      last menstrual period for pregnancies with gastroschisis was 20.4 years which was
      much younger than the national average of 28 years. Thirty-seven percent of these
      conceptions occurred during the first quarter of the year compared with the
      expected 25%. CONCLUSIONS: The incidence of gastroschisis has risen to a higher
      level than previously reported which, despite a marked association with young
      maternal age at conception, is not due to an increase in the teenage pregnancy
      rate. As the average length of inpatient stay in the neonatal intensive care unit
      for cases with this malformation is approximately four weeks, the rise has
      considerable cost implications. The increasing incidence may also offer
      opportunities to determine the cause of gastroschisis.

PMID- 9532997
TI  - Factors affecting the outcome of laparoscopic ovarian drilling for polycystic
      ovarian syndrome in women with anovulatory infertility.
AB  - OBJECTIVE: To describe and analyse the factors affecting the pregnancy rate of
      laparoscopic ovarian drilling for polycystic ovarian syndrome in women with
      anovulatory infertility. DESIGN: A retrospective study. SETTING: A specialist
      infertility clinic based at a teaching hospital in England. POPULATION: One
      hundred and eighteen women, for whom hospital records and follow up data were
      available, with polycystic ovarian syndrome who underwent laparoscopic ovarian
      surgery for anovulatory infertility over a five year period, between January 1991
      and December 1995. MAIN OUTCOME MEASURES: Ovulation and pregnancy rate. RESULTS:
      The cumulative conception rate 12 months after the treatment was 54%. Women who
      conceived following the surgery had a shorter duration of infertility, were
      treated with diathermy (rather than laser), had higher pre-operative luteinising
      hormone levels, were younger and were more likely to have ultrasonographic
      evidence of polycystic ovarian disease. Logistic multiple regression analysis
      showed that the duration of infertility, modality used in treatment (laser or
      diathermy) and the pre-operative levels were the main determinants of the
      outcome. CONCLUSION: Women with polycystic ovarian syndrome respond favourably to
      laparoscopic ovarian drilling. The success rate in women with infertility
      duration of less than three years, treated with diathermy, in whom the pre
      operative level was more than 10 IU/L reached 79%.

PMID- 9532996
TI  - Obstetric outcome in 232 ovum donation pregnancies.
AB  - OBJECTIVE: To study the obstetric outcome of ovum donation pregnancies. DESIGN: A
      retrospective analysis of 232 ovum donation pregnancies in the six years from
      1988 to 1993. SETTING: Infertility clinic in a private hospital. PARTICIPANTS:
      All ovum donation recipients that achieved pregnancy in the clinic during the
      stated time period. MAIN OUTCOME MEASURES: Percentages of live birth and
      miscarriages and ectopic pregnancies; number of sacs identified in the uterus at
      early (four weeks after transfer) and later scans; incidence of antepartum and
      postpartum haemorrhage; incidence of pregnancy-induced hypertension; incidence of
      preterm, low birthweight and small-for-gestational age babies; and incidence of
      operative deliveries. RESULTS: Of 232 pregnancies, 151 babies were born (live
      birth rate of 20%); and 81 were lost (57 before eight weeks, 17 after eight weeks
      and seven ectopic pregnancies). In nine cases there were no intrauterine sacs at
      the early scan (two 'chemical pregnancies' and seven ectopic pregnancies). In 169
      cases there was initially one intrauterine sac, ending with 102 singleton
      deliveries (60%); in 47 cases there were initially two intrauterine sacs, ending
      with 11 singleton deliveries (23%) and 32 twin deliveries (68%); in the seven
      cases where three sacs were identified initially, there were no singleton
      deliveries, three twin deliveries (one selective fetal reduction) and three
      triplet deliveries. Women with premature ovarian failures had a significantly
      higher pregnancy rate compared with those with functioning ovaries (P < 0.02).
      However, in the former group, the miscarriage rate was also significantly higher
      (P < 0.03) so that the number of term births was similar. The incidence of
      vaginal bleeding was 12% in the first trimester, 1.5% in the second trimester,
      and 2% in the third trimester. The incidence of postpartum haemorrhage was 12%.
      Thirty-two women had pregnancy-induced hypertension (23% of all deliveries). This
      occurred in 22/105 singletons (21%), 7/32 twins (22%) and in all three (100%) of
      the triplets. In the singleton group 13% of infants were preterm, 18% had a
      birthweight < 2.5 kg and 15% were < 3rd centile for birthweight at delivery
      (small-for-gestational age). Ovarian function was found to be the only factor
      that significantly influenced the incidence of small-for-gestational age babies
      (odds ratio 8.84; 95% confidence interval 1.1-70.0; P = 0.007). The overall
      operative delivery rate was 85% with the caesarean section rate being 69%.
      CONCLUSIONS: Women who become pregnant following oocyte donation should be
      considered obstetrically as high risk, especially those with ovarian failure
      because of the increased incidence of small-for-gestational age infants in these
      pregnancies. They are also at higher risk of pregnancy-induced hypertension and
      postpartum haemorrhage.

PMID- 9532998
TI  - Progesterone resistance in women who have had breast cancer.
AB  - OBJECTIVE: To investigate whether certain physiological responses to luteal
      progesterone are normal in women previously treated for breast cancer. DESIGN:
      Salivary progesterone concentrations, basal body temperatures, and breast blood
      flow changes (surface temperature method) were all recorded daily for one natural
      menstrual cycle. SETTING: Participants in the study made saliva collections and
      temperature measurements at home under semi-standardised conditions with
      supervisory visits by a project nurse. PARTICIPANTS: Twenty-five controls were
      compared with 30 women with previous breast cancer; all but three participants
      were parous and the average ages were 39 years (range 28-48) and 40 years (range
      29-46), respectively. On average the women with previous breast cancer had had
      surgery 2.4 years previously; the operation was usually mastectomy, leaving the
      contralateral breast for study. RESULTS: Follicular phase (day 1-14) oral
      temperature averages were statistically indistinguishable between women in the
      control group and those with previous breast cancer. Luteal progesterone profiles
      were considered in the normal range for the controls and patients. However, the
      women with previous breast cancer, on average, exhibited a significantly smaller
      rise in the luteal phase basal body temperature. Follicular phase breast surface
      temperature was significantly higher in the breast cancer group (+0.30 degree C).
      This group showed a highly significant reduction of the luteal heat cycle in
      their breasts. CONCLUSIONS: Two progesterone-mediated physiological mechanisms
      have been found to be significantly less responsive in women with previous breast
      cancer than controls. The literature has been reviewed. Progesterone resistance
      could be a clinical entity and could be important in carcinogenesis.

PMID- 9532999
TI  - The reliability of catheter-tip transducers for the measurement of intrauterine
      pressure in the third stage of labour.
AB  - In order to assess the reliability of intrauterine pressure measurements in the
      third stage of labour, catheter-tip transducers were used in 20 women randomly
      allocated into two groups of 10. In each case in the first group two catheters
      were tied together and introduced transcervically into the uterine cavity after
      delivery of the placenta. In each case in the second group two catheters were
      inserted independently into the same uterine cavity. The active and cumulative
      active pressures recorded from the pairs of catheters within each uterine cavity
      were compared. Comparison of individual active pressure readings from separate
      transducers revealed good agreement whether the catheters were tied together or
      were separate. Cumulative active pressure was very similar when assessed by each
      catheter in the same uterus. Intrauterine catheter-tip transducers can be used
      reliably to measure uterine activity in the third stage of labour although there
      may be minor contraction by contraction differences in recordings of individual
      active pressures.

PMID- 9533000
TI  - Computerised evaluation of fetal heart rate in post-term fetuses: long term
      variation.
AB  - Computerised fetal heart rate records were obtained between 1987 and 1993 using
      the Sonicaid System 8000 for a cross-sectional study of postdates fetal heart
      rate variation; 567 singleton pregnancies at 41 and 43 weeks provided 1502
      records. In all cases gestational age had been verified by ultrasound examination
      in early pregnancy. The mean minute range of the long term pulse interval
      variation, which is known to be correlated with fetal oxygenation was found to
      decrease progressively from an average value of 48.5 ms at 41 weeks to 46.4 ms
      and 42.4 ms at 42 and 43 or more weeks, respectively. When conservative
      management of postdate pregnancies is chosen, accurate measurements are needed to
      follow the evolution of fetal condition. Reference values for calculated pulse
      interval variation at later gestational ages are now provided.

PMID- 9533001
TI  - Power Doppler enhancement of the placenta by dehydroepiandrosterone sulphate in
      term pregnancy.
AB  - We studied the effect of dehydroepiandrosterone sulphate (DHAS) on placental
      blood flow in 11 women with an uncomplicated pregnancy between 37 and 39 weeks of
      gestation. Power Doppler enhancement of the placenta was performed before and 60
      minutes after the administration of a 200 mg intravenous dose of DHAS dissolved
      in 20 mL of 5% dextrose. Increased power Doppler enhancements of the placenta
      after DHAS injection were evident in each case studied. The power Doppler
      enhancement returned to the baseline imaging within 60 minutes. This DHAS loading
      test, assessed by means of power Doppler imaging, may be a useful technique when
      attempting to assess fetoplacental function in normal and high risk pregnancies.

PMID- 9533002
TI  - Uterine amyloidosis in menopause.

PMID- 9533003
TI  - Profound alcoholic ketoacidosis in pregnancy with survival of the fetus.

PMID- 9533004
TI  - Recombinant interferon-alpha therapy and meno-metrorrhagia.

PMID- 9533005
TI  - Customized fetal growth assessment.

PMID- 9533006
TI  - Amniotic membrane collagen content and type distribution in women with preterm
      premature rupture of the membranes in pregnancy.

PMID- 9533007
TI  - Randomised controlled trials in perinatal medicine: 2. Recruitment of a pregnant
      woman or her newborn child into more than one trial.

PMID- 9533008
TI  - Seizure prophylaxis in hypertensive pregnancies; a framework for making clinical
      decisions.

PMID- 9533009
TI  - Chemotherapy Foundation Symposium XV. Innovative Cancer Therapy for Tomorrow. New
      York City, New York, USA. November 12-14, 1997. Abstracts.

PMID- 9533010
TI  - Report of the Third International Workshop on Y Chromosome Mapping 1997.
      Heidelberg, Germany, April 13-16, 1997.

PMID- 9533011
TI  - Report and abstracts of the Sixth International Workshop on Human Chromosome 21
      Mapping 1996. Cold Spring Harbor, New York, USA. May 6-8,1996.

PMID- 9533012
TI  - A panel of transferable fragments of human chromosome 11q.
AB  - Cytogenetic and molecular studies have implicated one or more tumor suppressor
      genes on the long arm of human chromosome 11 in the malignant progression of
      several human solid tumors, including malignant melanoma and carcinomas of the
      breast, cervix, ovary, and lung. Microcell-mediated chromosome transfer of an
      intact copy of chromosome 11 into tumor cell lines has provided additional
      evidence of tumor suppressor gene function in melanoma, breast cancer, and
      cervical cancer. However, sublocalization of the region(s) conferring the tumor
      suppressive effect has been difficult. To facilitate mapping of tumor suppressor
      gene(s) on chromosome 11, we have generated a panel of 25 mouse donor cell lines
      containing neo-tagged fragments of human chromosome 11q which can be transferred
      into cell lines to test for tumor suppressor activity. The chromosome fragments
      in these cell lines have been characterized by fluorescence in situ hybridization
      with probes to human DNA and to the centromere of chromosome 11, and also by
      analysis of microsatellite markers spanning chromosome 11. Finally, to
      demonstrate the usefulness of these cell lines as donors for microcell-mediated
      chromosome transfer, two fragments were transferred into the human melanoma cell
      line UACC 903. This panel of selectable subchromosomal fragments, derived from
      the long arm of human chromosome 11, will be useful for the regional localization
      of tumor suppressors and other genes by means of functional assays.

PMID- 9533013
TI  - Assignment of the gene for ERC-55 (RCN2) to human chromosome band 15q22.33-
      >q24.1 by in situ hybridization.

PMID- 9533014
TI  - Assignment of the carnitine/acylcarnitine translocase gene (CACT) to human
      chromosome band 3p21.31 by in situ hybridization.

PMID- 9533016
TI  - A proposed nomenclature of the domestic cat karyotype.
AB  - High-resolution G- and Q-band patterns of cat (Felis catus) prometaphase
      chromosomes with more than 450 numbered bands are presented. This number
      represents approximately twice the number of bands per haploid set exhibited by
      feline chromosomes at mid-metaphase. A diagrammatic representation of G-banded
      cat chromosomes has already been described (O'Brien and Nash, 1982); however,
      precise numbering of bands and landmarks, as in the human karyotype and in the
      karyotypes of other domestic and laboratory animals, has not yet been available
      for the domestic cat karyotype, except for the RBG-banded ideograms constructed
      by Shibasaki et al. (1987) and Ronne and Storm (1995). In this report, we propose
      a numbering system for the G-banded ideogram reported previously (O'Brien and
      Nash, 1982) and an extended ideogram at the high-resolution level (473 numbered
      bands) as a contribution to the future standardization of the feline karyotype.

PMID- 9533015
TI  - Construction of two near-kilobase resolution restriction maps of the 5'
      regulatory region of the human apolipoprotein B gene by quantitative DNA fiber
      mapping (QDFM).
AB  - Quantitative DNA fiber mapping (QDFM) is a high-resolution technique for physical
      mapping of DNA. The method is based on hybridization of fluorescently labeled DNA
      probes to individual DNA molecules stretched on a chemically modified glass
      surface. We now demonstrate and validate a rapid QDFM-based approach for the
      mapping of multiple restriction sites and precise localization of restriction
      fragments in large genomic clones. Restriction fragments of a 70-kb P1 clone (P1
      70) containing the 5' region of the human apolipo-protein B gene (APOB) were
      subcloned and mapped along straightened P1-70 DNA molecules. Multicolor
      fluorescence in situ hybridization (FISH) and digital image analysis allowed us
      to rapidly position 29 restriction fragments, ranging in size from 0.5 kb to 8
      kb, and to map 43 restriction sites. The restriction map obtained by QDFM was in
      excellent agreement with information obtained by RecA-assisted restriction
      endonuclease (RARE) cleavage, long-range PCR, and DNA sequence analyses of the P1
      70 clone. These data demonstrate that QDFM is a rapid, reliable method for
      detailed restriction site-mapping of large DNA clones.

PMID- 9533017
TI  - Swine centromeric DNA repeats revealed by primed in situ (PRINS) labeling.
AB  - In swine, distinct centromeric satellite DNA families have been described that
      correspond to either all the metacentric chromosomes except the Y (Mc1) or all
      the acrocentric chromosomes (Ac2). Using primed in situ (PRINS) labeling, we show
      here that primers derived from various sequences specifically label the
      centromeres of different subgroups of chromosomes. Among five primers derived
      from centromeric sequences of acrocentric chromosomes reported to be very
      homogeneous, four recognize all the acrocentric chromosomes, whereas one labels
      prominently chromosome 17. For the metacentric chromosomes, six primers have been
      derived from several divergent sequences. Among these primers, two recognize all
      the metacentric chromosomes except 5, 10, and 12. Three other primers label small
      subsets of metacentric chromosomes, including the X and one or two additional
      chromosomes. The last primer is specific to chromosome 1. These preliminary
      results suggest that it should be possible to define specific primers for almost
      every swine chromosome. Already, some of the primers reported here permit a
      distinction between swine chromosomes difficult to differentiate without banding,
      such as the X chromosome and chromosome 9. Therefore, the PRINS technique using
      centromeric motifs constitutes an additional tool for cytogenetic studies in
      swine.

PMID- 9533018
TI  - The inwardly rectifying potassium channel subunit Kir2.2v (KCNJN1) maps to
      17p11.2-->p11.1.
AB  - Inwardly rectifying K+ (Kir) channels play important roles in various cellular
      functions in excitable and non-excitable cells. We recently cloned the human
      genes encoding the Kir channel subunits Kir2.2v (KCNJN1) and Kir2.2 (KCNJ12).
      However, the physiological role of Kir2.2v has not yet been clarified.
      Fluorescence in situ hybridization analysis of human metaphase chromosomes
      assigned both genes to 17p11.2-->p11.1. The presence of hybridization signals in
      the paracentromeric regions of both chromosomes 17 from two Smith-Magenis
      syndrome (SMS) patients indicated that Kir2.2v and Kir2.2 are not located within
      the minimum critical region of this syndrome.

PMID- 9533019
TI  - Mapping FRA11A, a folate-sensitive fragile site in human chromosome band 11q13.3.
AB  - FRA11A, a rare folate-sensitive fragile site assigned to 11q13.3, lies in an area
      of genomic instability associated with several diseases and amplification events.
      To map FRA11A, we used fluorescence in situ hybridization with yeast artificial
      chromosome and cosmid probes on metaphase chromosomes of patients expressing the
      fragile site. FRA11A was found situated centromeric to ACTN3 and telomeric to
      D11S913, these markers being within an interval of approximately 1 Mb in the
      11q13.3 region.

PMID- 9533020
TI  - Assignment of TCF1, TGM1, CALM1, CKB, THBS1, B2M, and FES in Ateles paniscus
      chamek (Platyrrhini, Primates).
AB  - Regional assignment of five markers to chromosome 2 of Ateles paniscus chamek
      (APC) confirmed a syntenic association similar to human (HSA) 12q + 14q + 15q.
      TCF1 was allocated to a shortest region of overlap (SRO) in APC 2p and found to
      be syntenic to PEPB, while TGM1, CALM1, THBS1, and B2M were assigned to APC 2q,
      being syntenic to NP, HEXA, and MPI. Conversely, markers close to HSA 14qter
      (CKB) and HSA 15qter (FES-IDH2) were relocated to other Ateles syntenic groups.
      Karyotypic comparisons showed an evident homoeology between APC 2p and HSA 12q,
      whereas APC 2q was similar to an HSA 14qter::HSA 15qter fusion product.

PMID- 9533021
TI  - Mapping of 22 new ESTs around a tumor suppressor gene and a senescence gene at
      6q16-->q21.
AB  - Twenty two expressed sequence tags (ESTs) have been mapped at the border of 6q16-
      >q21 and at the proximal end of 6q21, a candidate for two tumor suppressor genes
      and a senescence gene. Use of a translocation and deletion hybrid panel together
      with a 4-Mb YAC contig allowed us to precisely define the position of the ESTs.
      Thirteen ESTs were placed within the 4-Mb interval at the proximal portion of
      6q21 using a restriction map of the YAC contig, seven ESTs span a 2-Mb region on
      the 6q16-->q21 border, and two are distal to the contig. Refinement of the
      localization of these ESTs will provide substantial assistance in identifying new
      genes within the region 6q16-->q21.

PMID- 9533022
TI  - Assignment of MARK3 alias KP78 to human chromosome band 14q32.3 by in situ
      hybridization.

PMID- 9533023
TI  - Cloning and characterization of BAI2 and BAI3, novel genes homologous to brain
      specific angiogenesis inhibitor 1 (BAI1).
AB  - We have identified two novel human genes homologous to BAI1 (brain-specific
      angiogenesis inhibitor 1), an angiogenesis inhibitor that is a candidate for
      involvement in development of glioblastoma. Like BAI1, these two genes,
      designated BAI2 and BAI3, were specifically expressed in brain, and are likely to
      be expressed in the same type of cells. However, in spite of similar tissue
      specificity among the three BAI genes, only BAI1 is transcriptionally regulated
      by p53. BAI3 expression was absent in two of nine glioblastoma cell lines
      examined and was significantly reduced in three of the remaining seven. These
      data suggest that members of this novel gene family may play important roles in
      suppression of glioblastoma. BAI1, BAI2 and BAI3 were mapped to 8q24, 1p35 and
      6q12, respectively.

PMID- 9533024
TI  - Molecular cloning and chromosome mapping of rat phospholipase D genes, Pld1a,
      Pld1b and Pld2.
AB  - We have previously obtained three partial rat phospholipase D (PLD) cDNA
      fragments by a reverse transcriptase-polymerase chain reaction (RT-PCR) method
      using degenerate primers based on two conserved amino acid sequences in PLDs of
      human and yeast. The entire coding regions of these genes were isolated and
      sequenced. The longest clone, Pld1a encodes a 1075 amino acid (aa) protein that
      was highly similar (89% identity) to human PLD1a, especially in four conserved
      regions present in other PLDs. The nucleotide sequence of the second clone was
      identical to that of Pld1a except that the clone lacked 114 nucleotides
      corresponding to 38 aa in the middle. A shorter alternatively spliced form of
      human PLD1 (PLD1b) lacking the corresponding 38 aa was also identified.
      Therefore, the second clone (Pld1b) was considered to correspond to the rat
      counterpart of human PLD1b. The third clone, Pld2 encoding 933 aa was smaller
      than that of Pld1 and its aa identity to rat Pld1 was 56%. However, it contains
      four conserved regions and aa sequences of these regions are homologous to those
      of rat Pld1 and human PLD1. Its entire aa sequence was very similar (96%
      identity) to the recently cloned mouse PLD, Pld2. Chromosome locations of the
      Pld1a, Pld1b and Pld2 genes were determined in the rat and mouse by fluorescent
      in situ hybridization. As expected, both Pld1a and Pld1b clones were hybridized
      to the same chromosome regions. The Pld1 and Pld2 genes were localized to rat
      chromosome 2q23.3-->q24 proximal end and the proximal region of mouse Chromosome
      3B, and rat chromosome 10q23.3-->q24 proximal end and mouse Chromosome 11B3,
      respectively. They were mapped in regions where conserved linkage homology has
      been identified between the two species.

PMID- 9533025
TI  - Cloning, expression and mapping of a novel RING-finger gene (RNF5), a human
      homologue of a putative zinc-finger gene from Caenorhabditis elegans.
AB  - The RING-finger is a unique zinc-chelating domain involved in mediating protein
      protein interactions. The extensive sequence homology within the RING-finger
      domain allowed us to clone a novel member of the RING-finger family of genes.
      This cDNA clone, designated RNF5 (Ring-finger protein 5), contained an open
      reading frame of 540 nucleotides. Its predicted amino acid sequence revealed
      significant homology to a hypothetical protein encoded by Caenorhabditis elegans
      cosmid C16C10.7. The expression of RNF5 was detected in a variety of human
      tissues. The RNF5 gene was mapped by fluorescence in situ hybridization to
      chromosome 6p21.31. Radiation hybrid mapping further assigned RNF5 to a region
      proximal to the major histocompatibility complex (MHC) on chromosome 6. RNF5 is
      the third RING-finger gene identified in the region proximal to MHC raising the
      possibility that the RING-finger family of genes may exist as a cluster in this
      region.

PMID- 9533026
TI  - Assignment of the cat immunoglobulin heavy chain genes IGHM and IGHG to
      chromosome B3q26 and T cell receptor chain gene TCRG to A2q12-->q13 by
      fluorescence in situ hybridization.

PMID- 9533027
TI  - Assignment of dentin sialophosphoprotein (DSPP) to the critical DGI2 locus on
      human chromosome 4 band q21.3 by in situ hybridization.

PMID- 9533028
TI  - Assignment of trophoblast/endometrial epithelium cell adhesion molecule trophinin
      gene TRO to human chromosome bands Xp11.22-->p11.21 by in situ hybridization.

PMID- 9533029
TI  - Detailed map of a region commonly amplified at 11q13-->q14 in human breast
      carcinoma.
AB  - Amplification of loci present on band q13 of human chromosome 11 is a feature of
      a subset of estrogen receptor positive breast carcinomas prone to metastasis. As
      many as five distinct amplification units have been described on 11q13. They
      include particularly a genomic area encompassing the GARP gene at 11q13.5-
      >q14.1. We have reassessed our current knowledge of this region, located
      telomeric to CCND1 and EMS1, which is amplified in 7-10% of mammary tumors. The
      loose definition of the driving forces of these amplification events led us to
      map accurately the boundaries of the amplifiable region, and thus to contribute a
      physical and transcriptional map of a 3-Mb region of chromosome 11. Four new
      genes were placed on the regional map, namely CBP2, CLNS1A, UVRAG, and PAK1. We
      have narrowed the core of the 11q13-->q14 amplicon to a 350-kb area encompassing
      D11S533, mostly on its telomeric side. The map reported here represents an
      indispensable step toward sequencing the entire region, and thus toward
      uncovering gene(s) which play(s) a critical role in breast cancer progression.

PMID- 9533030
TI  - Cytochrome b in human complex II (succinate-ubiquinone oxidoreductase): cDNA
      cloning of the components in liver mitochondria and chromosome assignment of the
      genes for the large (SDHC) and small (SDHD) subunits to 1q21 and 11q23.
AB  - Complex II (succinate-ubiquinone oxidoreductase) is an important enzyme complex
      in both the tricarboxylic acid cycle and the aerobic respiratory chains of
      mitochondria in eukaryotic cells and prokaryotic organisms. In this study, the
      amino acid sequences of the large (cybL) and small (cybS) subunits of cytochrome
      b in human liver complex II were deduced from cDNAs isolated by homology probing
      with mixed primers for the polymerase chain reaction. The mature cybL and cybS
      contain 140 and 103 amino acids, respectively, and show little similarity to the
      amino acid sequences of the subunits from other species in contrast to the highly
      conserved features of the flavoprotein (Fp) subunit and iron-sulfur protein (Ip)
      subunit. From hydrophobicity analysis, both cybL and cybS appear to have three
      transmembrane segments, indicating their role as membrane-anchors for the enzyme
      complex. Histidine residues, which are possible heme axial ligands in cytochrome
      b of complex II, were found in the second transmembrane segment of each subunit.
      The genes for cybL (SDHC) and cybS (SDHD) were mapped to chromosome 1q21 and
      11q23, respectively by fluorescent in situ hybridization (FISH).

PMID- 9533031
TI  - cDNA sequence, genomic organization and mapping of PDE6D, the human gene encoding
      the delta subunit of the cGMP phosphodiesterase of retinal rod cells to
      chromosome 2q36.

PMID- 9533032
TI  - Assignment of secreted phosphoprotein 24 (SPP2) to human chromosome band 2q37-
      >qter by in situ hybridization.

PMID- 9533033
TI  - Assignment of the aminopeptidase B gene (RNPEP) to human chromosome 1 band q32 by
      in situ hybridization.

PMID- 9533034
TI  - Assignment of the cat p53 tumor suppressor gene (TP53) to cat chromosome E1p14-
      >p13 by fluorescence in situ hybridization.

PMID- 9533035
TI  - Assignment of protease, serine-like 1 (PRSSL1) to human chromosome 19q13 by in
      situ hybridization and radiation hybrid mapping.

PMID- 9533036
TI  - Assignment of the microvascular endothelial differentiation gene 1 (MDG1) to
      human chromosome band 14q24.2-->q24.3 by fluorescence in situ hybridization.

PMID- 9533037
TI  - Assignment of the pyruvate carboxylase gene to rat chromosome band 1q43 by in
      situ hybridization.

PMID- 9533038
TI  - FISH analysis of translocations in lymphocytes of children exposed to the
      Chernobyl fallout: preferential involvement of chromosome 10.
AB  - Using whole-chromosome painting probes, we have analyzed the frequency of
      translocations of chromosomes 1, 3, and 10 in peripheral lymphocytes of 20 Gomel
      (Belarus) children, including both thyroid tumor affected and healthy
      individuals. Gomel was one of the most heavily radiocontaminated areas due to
      fallout from the Chernobyl nuclear power plant disaster. As controls, 14 healthy
      children from Pisa (Italy) were investigated simultaneously. Translocation rates
      were significantly higher in the tumor affected (1.71 +/- 0.68) and healthy Gomel
      children (2.69 +/- 0.50) than in the Italian controls (0.79 +/- 0.24). We also
      observed, in healthy Gomel children, an approximately three-fold higher frequency
      of chromosome 10 translocations compared to translocations affecting chromosomes
      1 or 3 (P = 0.0096), a difference that was made even larger (about four fold)
      after correcting for chromosome size (P = 0.0009). This finding suggests a
      preferential involvement of chromosome 10 in translocations induced in vivo by
      low levels of ionizing radiation.

PMID- 9533039
TI  - Chromosomal assignment of human endogenous retrovirus K (HERV-K) env open reading
      frames.
AB  - The haploid human genome contains at least one human endogenous retrovirus K
      (HERV-K) env gene displaying an open reading frame, as evidenced by the high
      antibody titers against HERV-K Env in germ cell tumor patients at the time of
      tumor detection. However, the chromosomal assignment of an intact HERV-K env
      sequence is complicated by the existence of 25-30 HERV-K copies per haploid human
      genome. Recently, we reported the application of the protein truncation test
      (PTT) to chromosomally assign HERV-K gag open reading frames. Here, we set out to
      determine the chromosomal distribution of full-length HERV-K env genes. As
      demonstrated by somatic hybrid mapping and the PTT, HERV-K env open reading
      frames were found on human chromosomes 7, 19, and Y. By sequencing chromosome
      specific HERV-K env subregions, we assigned two recently reported intact HERV-K
      sequences on human chromosomes 7 and 19, respectively. Chromosomes 7 and 19 and
      the Y are furthermore candidates for harboring a putative completely intact HERV
      K locus.

PMID- 9533040
TI  - The nature of G-bands analyzed by chromosome stretching.
AB  - To investigate the nature of G-banding, chromosome stretching was performed on
      chromosome 6 at the 400-band level of normal human lymphocytes that had been
      cultivated and harvested using standard techniques. The GTG-banding patterns of
      five stretched chromosomes 6 were compared microscopically with each other and
      found to be identical at the 1,400-band level. A high-resolution ideogram at the
      1,400-band level was constructed. The banding pattern at this level appeared to
      be very regular, with all dark bands at the 400-band level splitting into three
      to six dark subbands. While the dark subbands observed at the 1,400-band level
      seem to derive solely from the dark bands seen at the 400-band level, light bands
      visible at the 400-band level do not split into subbands, which is in contrast to
      the published (ISCN, 1995) ideograms. The splitting process, which was analyzed
      on the video monitor in more detail, shows that chromosome stretching is due
      mainly to the appearance of light subbands flanked by dark subbands. To shed more
      light on this phenomenon, the staining intensity of the dark bands and their
      subbands was measured while the chromosomes were stretched from the 400- to the
      1,400-band level. At first, staining intensity was found to diminish in inverse
      proportion to the elongation of the chromosome, but then remained relatively
      unaffected until the dark subbands were gradually split up. After stretching to
      the 1,400-band level, these dark subbands were followed by newly appearing small
      light subbands, which were about the same size as the stretched light bands
      visible at the 400-band level. The results indicate that, in general, the light
      bands of human chromosomes are the preferentially stretched chromosome regions
      and that the resolution-dependent characteristic banding pattern of human
      chromosomes is mainly based on a fixed hierarchy of the stretchability of
      chromosomes.

PMID- 9533041
TI  - Social Security Bulletin. Annual statistical supplement, 1997.

PMID- 9533042
TI  - Annual report on Findings of Infectious Agents in Japan. 1994.

PMID- 9533043
TI  - Proceedings of the 6th and 7th scientific sessions of the Japanese Society of
      Echocardiography.

PMID- 9533044
TI  - SCVIR 23rd annual scientific meeting. San Francisco, California, USA. February 28
      March 5, 1998.

PMID- 9533045
TI  - The 2nd International Conference on Osteoporosis. Osaka and Nara, Japan. November
      13-16, 1997. Abstracts.

PMID- 9533046
TI  - Osteoarthritis.

PMID- 9533047
TI  - Kinematic posterior cruciate ligament-retaining total knee replacements. A 10
      year survivorship study of 445 arthroplasties.
AB  - Survival was tested in 445 primary Kinematic knee replacements performed between
      January 1981 and December 1990. Three criteria were applied to indicate failure:
      1) revision or recommended revision, 2) presence of moderate to severe pain or
      revision, and 3) lost to follow-up or revision. Using these three criteria, the
      survival rate at 10 years was 96%, 78%, and 69%, respectively. At last follow-up
      examination, 84% of knees had good or excellent Bristol knee scores with mean
      range of motion 100 degrees. Overall, 11 knees (2.5%) have been revised and 27
      cases (6%) were graded as failures due to presence of moderate to severe pain at
      the time of the last evaluation. These results indicate that the posterior
      cruciate ligament-retaining Kinematic prosthesis provides satisfactory function
      and survival up to 10 years.

PMID- 9533049
TI  - Primary total knee arthroplasty in stiff and ankylosed knees.
AB  - This study reviewed 71 patients who underwent 82 total knee arthroplasties
      between 1974 and 1987. All patients had severe limitations of motion
      preoperatively with a total preoperative arc of motion of < or = 50 degrees.
      Follow-up ranged from 2 to 12 years (average: 5.3 years). The average
      preoperative knee score was 38 (range: 14 to 54). The average preoperative arc of
      motion was 36 degrees (range: 0 degree to 50 degrees), with an average flexion
      contracture of 22 degrees average maximum flexion of 58 degrees. Postoperatively,
      the average knee score was 80 (range: 0 to 98). The average postoperative arc of
      motion was 93 degrees (range: 35 degrees to 130 degrees), with an average maximum
      flexion of 94 degrees. Nine knees had 5 degrees flexion contractures, while 5
      knees had 10 degrees flexion contractures. Postoperatively, no knee had a flexion
      contracture > 10 degrees. Two knees had a decreased range of motion
      postoperatively. Two knees with severe flexion-valgus deformities developed
      peroneal nerve palsies that both resolved. Total knee arthroplasty in stiff or
      ankylosed knees can produce good or excellent results and can lead to significant
      improvement in range of motion and pain.

PMID- 9533048
TI  - The effect of pretwisting the ACL autograft on knee laxity.
AB  - This study was undertaken to determine whether pretwisting the bone-patellar
      tendon-bone autograft during primary anterior cruciate ligament (ACL)
      reconstruction had any effect on knee laxity. Patients were assigned to have
      twisted or nontwisted autografts based on the date of ACL reconstruction. The
      control group was comprised of 60 patients without graft twist, and the twist
      group was comprised of 60 patients who had 90 degrees of external twist applied
      to the graft prior to tibial fixation to reproduce the anatomic external twist of
      the native ACL. The average patient age was 28.8 years for the control group and
      28.3 years for the twist group. Males accounted for 68% of the control patients
      and 73% of the twist patients. Meniscal tears were present in 45% of control and
      52% of twist patients. Reconstructions were performed using an endoscopic, single
      incision technique with interference screw fixation in the femur. Follow-up
      examination with KT-2000 arthrometry was performed when patients were within 10%
      of strength of the uninjured leg by isokinetic testing. KT-2000 testing at 30 lb
      revealed a mean side-to-side difference for reconstructed versus noninvolved
      knees of 1.06 for control patients and 1.08 for twist patients. The difference
      between the two groups was not statistically significant. All but three control
      and two twist patients had a Lachman and an anterior drawer examination graded as
      0 to 1+. This difference also was not statistically significant. There were no
      clinical failures in either group. Furthermore, there was no statistically
      significant difference between groups clinically or by arthrometry when comparing
      tibial fixation with an interference fit screw versus suture fixation to a
      unicortical post. These results indicate that pretwisting the patellar tendon
      autograft in ACL reconstruction has no significant short-term effect on knee
      laxity as determined by instrumented testing or clinical examination.

PMID- 9533050
TI  - Biomechanical evaluation of lateral patellar dislocations.
AB  - This investigation was undertaken to identify the structures torn within the
      medial retinaculum and localize the injury site anatomically following acute
      lateral dislocation of the patella in a cadaver model. The patellae of 10 fresh
      frozen cadavers were translated laterally 135% of the patella width on a
      universal testing instrument. Magnetic resonance imaging (MRI) was performed on
      all specimens prior to testing and immediately following testing. Anatomical
      dissection also was performed on the medial retinaculum following testing.
      Dissection revealed avulsion fractures from the inferomedial border of the
      patella in 8 of the 10 knees. The medial patellofemoral ligament was injured in 8
      of the 10 knees; the location of the injury varied. Tears of the medial
      patellofemoral ligament from the femur in 6, a midsubstance tear in 1, and
      stretch in 1 knee were noted. In a knee with a femoral-sided tear, an avulsion
      fracture of the medial patellofemoral ligament was identified. None of the
      cadaver knees demonstrated tears of the lateral retinaculum or medial
      patellotibial ligaments on dissection. Review of the MRIs revealed a medial
      retinaculum tear in 6 of the 10 knees. Two tears from the femur, 3 from the
      patella, and 1 tear from both the patella and femur were noted. An avulsion
      fracture was noted from the inferomedial patellar border in 3 of the 10 knees. No
      pathology was noted on 4 of the MRIs. When anatomically correlated, the 3
      patellar retinacular tears and 3 avulsion fractures noted on MRI represented a
      tear of the medial patellomeniscal ligament from the patella. The femoral-sided
      tear represented a tear of the medial patellofemoral ligament from the femur. An
      appreciation of the spectrum of injury to the medial retinaculum may aid in the
      diagnosis of an acute dislocation of the patella and help establish the
      anatomical structures damaged. The pathology demonstrated in this study may
      explain the diversity of injury seen clinically. Whereas an avulsion fracture
      from the patella may represent the medial patellomeniscal ligament, a femoral
      sided retinacular tear may represent the medial patellofemoral ligament. This may
      lead to future refinements of surgical options and anatomic restoration of the
      damaged structure.

PMID- 9533051
TI  - Migration of femoral interference screw after anterior cruciate ligament
      reconstruction.

PMID- 9533052
TI  - Loose bodies of a benign neurilemoma in the knee joint.

PMID- 9533053
TI  - Osteoarthritis of the knee. Introduction and overview of treatment.

PMID- 9533055
TI  - Arthroscopic surgery and a new classification system.
AB  - Arthroscopic lavage and debridement is of significant value in the earlier stages
      of arthritis. This is probably through the removal or dilution of enzymes that
      are part of the degradative process of osteoarthritis. Mechanical problems such
      as meniscal tears and loose bodies also can be addressed at the same time.
      However, patients must be selected carefully for arthroscopic treatment. A
      severity scale is proposed based on clinical and radiological findings that
      should indicate in advance those patients who will have the greatest opportunity
      for improvement from an arthroscopic procedure. Critics have said that lavage and
      debridement does nothing to change the natural history of the disease and is no
      more than a placebo effect. While there is no strong evidence to suggest that it
      does modify the natural history of the disease, it definitely improves the
      quality of life for a significant period of time, with little in the way of
      complications or morbidity associated with the procedure. The placebo effect
      might explain some of the results, but the placebo effect is well-known in
      medicine, and if it does produce a positive result in terms of reduction of
      symptoms, it cannot be entirely discounted. The biological resurfacing of a joint
      under arthroscopic control is the challenge facing orthopedic surgeons today.
      Healing and restoration of articular tissues back to some functional biological
      state would seem to be a reasonable goal. If this can be achieved, the future
      will lie in the salvage of joints through arthroscopic procedures rather than the
      replacement of joints by arthroplasty.

PMID- 9533054
TI  - Current treatment options for the restoration of articular cartilage.
AB  - Over the past several decades, much has been learned about articular cartilage
      and its physiological capacity to restore itself. While articular cartilage does
      appear to have some regenerative capabilities, it appears to lose this capacity
      over a period of time, making restoration of articular surfaces more and more
      difficult. To date, no technique has been completely successful in achieving
      exactly normal regenerative articular cartilage. Arthroscopic lavage and
      debridement provides temporary relief of symptoms. This probably works by
      removing degradative enzymes that contribute to synovitis and also to the further
      breakdown of articular cartilage. Bone marrow stimulation techniques such as
      abrasion arthroplasty, drilling, and microfracture produce only fibrocartilage
      and therefore do not offer a long-term cure. Perichondral and periosteal
      interposition grafts produce repair tissue that is similar to hyaline cartilage
      but also lack the mechanical durability. Like bone marrow stimulation techniques,
      interposition grafts introduce precursor cells, which have a tendency to
      differentiate along lines other than cartilage. This leads to an inferior quality
      of repair tissue. Currently, chondrogenic-stimulating factors and artificial
      matrices are currently being researched and developed. Much has been learned
      about the various growth factors that stimulate chondrocyte differentiation and
      extracellular matrix production, but to date, there has not been a clinical
      technique that has shown any long-term promise. Ultimately, the goal will be to
      take precursor cells from an easily accessible source such as the iliac crest,
      mix them with growth factors that have been derived genetically in the lab, and
      provide an artificial matrix that in combination can produce restoration of
      articular cartilage at minimal cost and patient morbidity. Autologous
      osteochondral transplant systems have shown encouraging results but there are
      still problems. Graft matching and contouring to the recipient articular surface
      is difficult. Donor sites can be a limiting factor. Furthermore, the
      fibrocartilaginous interface between the donor and recipient site may contribute
      to breakdown in the long run. Autologous chondrocyte implantation is a biological
      repair process that also has shown encouraging results. It must be remembered
      that this is not normal articular cartilage--it is only hyaline-like cartilage.
      The technique is expensive and is technically difficult to perform. There are no
      randomized prospective studies that compare the natural history of the repair
      tissue to that of other forms of repair tissue. Long-term functional outcome is
      still a significant question mark. In addition, it has not been shown that
      autologous chondrocyte implantation can prevent degenerative changes. In the
      future, we probably will see delivery systems using stimulating growth factors,
      chondrocytes, and synthetically derived matrices. When placed in combination and
      with the right mechanical stimuli, we may ultimately achieve true restoration of
      articular cartilage.

PMID- 9533056
TI  - Surgical treatment. Osteotomy and unicompartmental arthroplasty.

PMID- 9533057
TI  - Surgical treatment. Total knee arthroplasty.
AB  - Modern total knee arthroplasty is a successful surgical procedure for the vast
      majority of patients. The success of knee replacement has extended its
      indications, and this has created controversy. Surgical principles for total knee
      arthroplasty include: establishment of proper mechanical alignment, preservation
      of joint line, maintenance of joint stability, maintaining extensor mechanism
      function and rigid fixation of components. Continued research and evaluation of
      long-term arthroplasty results will aid in answering current controversies
      surrounding knee replacement.

PMID- 9533058
TI  - Pharmaceutical care in medical progressive care patients.
AB  - OBJECTIVE: To develop, implement, and assess the outcomes of a system for
      providing pharmaceutical care to medical progressive care patients. METHODS: A
      system for providing pharmaceutical care was developed and implemented for an 8
      week period beginning in June 1995. Both patient care outcomes and drug therapy
      cost change from the intervention period were compared with those of an 8-week
      baseline period. Variables compared included unit length of stay, hospital length
      of stay, transfers to the intensive care unit, readmissions, and adverse drug
      reactions requiring treatment. Differences between periods for these variables
      were assessed by using chi 2 tests and t-tests with alpha set at p less than
      0.05. The clinical significance of the interventions were assessed independently
      by four physicians: two intensivists and two internists. The total drug therapy
      cost change from the intervention period was calculated as follows: total cost
      avoidance from individual recommendations subtracted from the total cost incurred
      from individual recommendations. RESULTS: The pharmacist evaluated 152 patients
      during the intervention period. A total of 235 pharmacotherapy recommendations
      were made on 103 patients, of whom 86.4% were accepted. Significantly fewer
      adverse drug reactions (ADRs) received treatment during the intervention period
      (p = 0.027). The mean unit length of stay was lower during the intervention
      period (4.8 +/- 3.7 d) than during the baseline period (6.0 +/- 5.6 d); however,
      this difference was not significant (p = 0.053). Individual physician assessment
      of the pharmacists' recommendations revealed that 75.8% were considered somewhat
      significant, significant, or very significant. The total drug therapy cost change
      from the intervention period was -$6534.53. The projected annual drug therapy
      cost reduction from this study is $42,474.45. CONCLUSIONS: The provision of
      pharmaceutical care to medical progressive care patients was associated with a
      substantial decrease in drug therapy cost and a decrease in the number of ADRs
      that required treatment.

PMID- 9533059
TI  - Comparison of phenytoin serum concentrations in premature neonates following
      intravenous and oral administration.
AB  - OBJECTIVE: To compare the serum concentrations attained following intravenous and
      oral administration of phenytoin in premature neonates. DESIGN: A prospective,
      uncontrolled study was conducted over 6 years. Phenhydan concentrate for infusion
      (Desitin, Hamburg, Germany) was used for intravenous infusion, and Epanutin
      suspension (Parke-Davis, Freiburg, Germany) was used for oral therapy. Blood
      samples were analyzed by using a fluorescence polarization immunoassay analyzer
      TDx model by Abbott Laboratories. SETTING: A university-affiliated district
      hospital. PARTICIPANTS: Twenty premature neonates who were administered
      intravenous and/or oral phenytoin between February 1991 and February 1997. MAIN
      OUTCOME MEASURES: Serum phenytoin concentrations on intravenous and oral
      phenytoin. RESULTS: Nine patients received intravenous (group A) and 15 patients
      received oral (group B) therapy. Mean +/- SD postnatal age (41 +/- 8.7 vs. 48 +/-
      17 d; p = 0.03) and actual body weight (1.56 +/- 0.38 vs. 1.88 +/- 0.75 kg; p =
      0.02) were slightly higher in group B. There were no significant differences
      between the groups in mean +/- SD gestational age (26.1 +/- 1.37 vs. 26.9 +/-
      3.30 wk), 5-minute Apgar score (8.7 +/- 1.11 vs. 7.7 +/- 2.26), daily dosage (8.1
      +/- 3.86 vs. 8.1 +/- 4.21 mg/kg/d), and phenytoin serum concentration (8.7 +/-
      7.36 vs. 9.6 +/- 5.83 micrograms/mL). CONCLUSIONS: Contrary to data in the
      current literature, reliable serum concentrations in premature neonates were
      achieved by oral administration of phenytoin suspension. Oral therapy offers a
      number of advantages and considerably reduces the cost of therapy. Due to
      substantial variations in phenytoin pharmacokinetics in neonates, close
      monitoring of serum concentrations is required. Further investigation is required
      to confirm these results, especially in neonates younger than 20 days' postnatal
      age and those receiving products other than Epanutin.

PMID- 9533060
TI  - Effect of ranitidine on the pharmacokinetics of orally administered eprosartan,
      an angiotensin II antagonist, in healthy male volunteers.
AB  - OBJECTIVE: To assess the effect of ranitidine on the pharmacokinetics of
      eprosartan in healthy male volunteers. DESIGN: Single-center, randomized, open
      label, two-period, period-balanced, crossover study. PATIENTS: Seventeen healthy
      men aged 19 to 43 years. INTERVENTION: In each period (separated by a > or = 7 d
      washout), subjects received a single 400-mg oral dose of eprosartan alone, or a
      single oral dose of eprosartan 400 mg and ranitidine 150 mg on day 4 after 3 days
      of ranitidine 150 mg twice daily. Serial pharmacokinetic samples were obtained
      for up to 24 hours following eprosartan dosing. MAIN OUTCOME MEASURES: Plasma and
      urine eprosartan concentrations during each treatment session. RESULTS:
      Eprosartan maximum concentration (Cmax), the AUC from time-zero to the last
      quantifiable concentration (AUC0-t), and renal clearance (Cl(r)) values were
      approximately 7%, 11%, and 4% lower, respectively, when administered with
      ranitidine compared with eprosartan alone. The 95% CIs for the ratio of
      eprosartan plus ranitidine compared with eprosartan alone were 0.81 to 1.07, 0.77
      to 1.03, and 0.64 to 1.43, for Cmax, AUC0-t, and Cl(r), respectively, indicating
      no statistically significant difference between regimens. CONCLUSIONS: Repeated
      doses of ranitidine did not have a marked effect on the single-dose
      pharmacokinetics of eprosartan.

PMID- 9533061
TI  - Clostridium difficile toxin-induced colitis after use of clindamycin phosphate
      vaginal cream.
AB  - OBJECTIVE: To report a case of toxin-positive Clostridium difficile-induced
      colitis (CDIC) after use of clindamycin phosphate vaginal cream. CASE SUMMARY: A
      25-year-old postpartum white woman developed multiple watery stools and abdominal
      cramping on day 6 of therapy with clindamycin vaginal cream for bacterial
      vaginosis. She received no other concomitant medications. The patient's stool
      sample was found to be positive for the C. difficile toxin. Due to the costs and
      risks of standard therapy, we decided to manage the patient supportively.
      Complete resolution of the diarrhea occurred shortly thereafter. DISCUSSION: No
      published clinical studies in patients receiving clindamycin vaginal cream for
      bacterial vaginosis have documented C. difficile toxin in stool samples of
      patients with diarrhea. Approximately 5-6% of intravaginal clindamycin is
      absorbed in the bloodstream, making systemic effects possible. CONCLUSIONS: This
      report indicates clindamycin phosphate vaginal cream as the most probable cause
      of CDIC due to the temporal relationship between the occurrence of diarrhea and
      clindamycin administration, lack of concomitant medications, and documentation of
      C. difficile toxin.

PMID- 9533062
TI  - Antacid-induced hypermagnesemia in a patient with normal renal function and bowel
      obstruction.
AB  - OBJECTIVE: To report a case of severe hypermagnesemia caused by magnesium
      hydroxide in a woman with normal renal function. CASE SUMMARY: A 42-year-old
      Hispanic woman with schizophrenia and bipolar affective disorder was transported
      from jail to the emergency department with confusion, abdominal pain, vomiting,
      and constipation. She had been treated in jail with magnesium hydroxide, ordered
      as milk of magnesia 30 mL po each night and Maalox 30 mL po three times daily.
      Additional medications included lithium carbonate 300 mg po three times daily,
      chlorpromazine 150 mg po three times daily, benztropine mesylate 1 mg po twice
      daily, and docusate sodium 100 mg po each morning. Her temperature was 35.1
      degrees C, blood pressure 108/58 mm Hg, heart rate 112 beats/min, and respiratory
      rate 24 breaths/min. She would respond only briefly to voice or painful stimuli.
      Her abdomen was distended and diffusely tender. Laboratory tests included serum
      magnesium concentration 9.1 mEq/L (normal 1.3-2), blood urea nitrogen 16 mg/dL (8
      22), creatinine 0.9 mg/dL (0.5-1.1), calcium 3.9 mEq/L (4.2-5.2), and lithium 1.0
      mEq/L. A laparotomy was performed, and an adhesive band from a previous
      oophorectomy was found to be compressing the sigmoid colon. Hypermagnesemia,
      hypothermia, and hypotension continued in the intensive care unit. Despite
      successful treatment of the hypermagnesemia with calcium, intravenous fluids, and
      furosemide, the patient's cardiac rhythm degenerated into fatal, pulseless
      electrical activity on postoperative day 2. DISCUSSION: This case of severe
      hypermagnesemia from magnesium hydroxide ingestion illustrates many of the risk
      factors for hypermagnesemia in patients with normal renal function. People using
      magnesium-containing medications for relief of gastrointestinal distress may be
      at increased risk for hypermagnesemia. A brief review of magnesium physiology,
      clinical effects, and treatment is provided. Frequent use of the laboratory to
      identify hypermagnesemia is encouraged because it is often a clinically
      unexpected finding and responds well to early treatment.

PMID- 9533063
TI  - Continuous fentanyl infusion: use in severe cancer pain.
AB  - OBJECTIVE: To describe the use of a continuous fentanyl infusion in an adult
      cancer patient. CASE SUMMARY: A 66-year-old white woman diagnosed with metastatic
      pancreatic carcinoma required hospital admission for pain control after receiving
      five different chemotherapy regimens. Morphine 2 mg/h i.v. was initiated and the
      dosage was titrated upward to a total of 6613 mg/d by hospital day 16. As
      hospital supplies of opioids became depleted over a holiday weekend, therapy was
      changed to a continuous infusion of hydromorphone 70 mg/h on hospital day 17,
      then changed to a continuous fentanyl infusion beginning with a dosage of 500
      micrograms/h. The fentanyl dosage was titrated to 4250 micrograms/h by hospital
      day 20. She died comfortably on hospital day 22 while receiving this dosage.
      DISCUSSION: Continuous infusions of opioids, particularly morphine and
      hydromorphone, are frequently used for control of cancer pain and are safe and
      effective when administered by this route. Transdermal fentanyl has been shown to
      effectively manage chronic cancer pain, and use of continuous subcutaneous
      fentanyl has been reported. However, reports of continuous intravenous fentanyl
      infusion in the cancer pain literature are limited. Our patient achieved good
      pain control with a continuous infusion of fentanyl 4250 micrograms/h.
      CONCLUSIONS: Continuous fentanyl infusion should be considered for the treatment
      of cancer pain in patients requiring high doses who become refractory to other
      opioids, when other opioids cause intolerable adverse effects, when patients have
      a true morphine allergy, or when high-dose requirements threaten to deplete
      existing stock of alternate opioids.

PMID- 9533064
TI  - Levofloxacin and sparfloxacin: new quinolone antibiotics.
AB  - OBJECTIVE: To discuss the pharmacology, pharmacokinetics, spectrum of activity,
      clinical trials, and adverse effects of levofloxacin and sparfloxacin, two new
      fluoroquinolone antibiotics. DATA SOURCES: Literature was identified by a MEDLINE
      search from January 1985 to September 1997. Abstracts and presentations were
      identified by review of program abstracts from the Interscience Conference on
      Antimicrobial Agents and Chemotherapy from 1988 to 1996. STUDY SELECTION:
      Randomized, controlled clinical studies were selected for evaluation; however,
      uncontrolled studies were included when data were limited for indications
      approved by the Food and Drug Administration (FDA). In vitro data were selected
      from comparison trials whenever available. Only in vitro trials that provided
      data on the minimum inhibitory concentrations required to inhibit 90% of isolates
      were used. Data from North American studies were selected whenever available.
      DATA EXTRACTION: Data were evaluated with respect to in vitro activity, study
      design, clinical and microbiologic outcomes, and adverse drug reactions. DATA
      SYNTHESIS: Levofloxacin and sparfloxacin are active against pathogens frequently
      involved in community-acquired upper and lower respiratory tract infections,
      including Streptococcus pneumoniae, Haemophilus influenzae, Moraxella
      catarrhalis, Mycoplasma pneumoniae, Legionella pneumophila, and Chlamydia
      pneumoniae. Both compounds have enhanced activity compared with ciprofloxacin
      against most gram-positive bacteria, including enterococci, streptococci, and
      staphylococci, and retain good activity against most Enterobacteriaceae and
      Pseudomonas aeruginosa. Sparfloxacin has greater anaerobic activity than
      levofloxacin, which is more active than ciprofloxacin or ofloxacin. Although many
      clinical studies are available only in abstract form, the clinical data
      demonstrate that these new quinolones are effective for most community-acquired
      upper and lower respiratory tract infections, urinary tract infections,
      gonococcal and nongonococcal urethritis, and skin and skin structure infections.
      FDA-approved indications are limited for both compounds to date. CONCLUSIONS:
      Levofloxacin and sparfloxacin have improved gram-positive activity compared with
      that of older fluoroquinolones, and are administered once daily. Sparfloxacin
      associated photosensitivity may limit its therapeutic usefulness. Clinical trials
      confirm that these agents are as effective as traditional therapies for the
      management of community-acquired pneumonia, acute exacerbations of chronic
      bronchitis, sinusitis, urinary tract infections, acute gonococcal and
      nongonococcal urethritis, and skin and skin structure infections.

PMID- 9533065
TI  - Troglitazone: review and assessment of its role in the treatment of patients with
      impaired glucose tolerance and diabetes mellitus.
AB  - OBJECTIVE: To introduce troglitazone (CS-045, Rezulin), a new oral antidiabetic
      agent and discuss its pharmacology, therapeutics, pharmacokinetics, dosing
      guidelines, adverse effects, drug interactions, and clinical efficacy. DATA
      SOURCES: A MEDLINE database search was completed to identify relevant articles
      including reviews, recent studies and abstracts, and data from Parke-Davis. STUDY
      SELECTION: Due to the small number of published human studies available, some
      data are derived from animal studies and abstracts of human studies. Studies and
      abstracts chosen summarize the clinical action of troglitazone in healthy
      volunteers, in subjects with impaired glucose tolerance, and in patients with
      diabetes mellitus. Three of the six published human studies used subjects in a
      placebo-controlled, multicenter, randomized environment (type 2 diabetic patients
      or obese subjects with insulin resistance). DATA EXTRACTION: All clinical trials
      available, including unpublished reports, were reviewed. DATA SYNTHESIS:
      Troglitazone is the first member of a new class of medications, the
      thiazolidinediones, to be approved for clinical use. Troglitazone increases
      insulin sensitivity in skeletal muscle and in hepatic and adipose tissue. It has
      been shown to decrease hepatic glucose output while having no effect on
      stimulating insulin secretion from the pancreatic beta-cells. Its metabolic
      effects decrease fasting and postprandial hyperglycemia, insulin concentrations,
      and triglyceride concentrations, while increasing high-density lipoprotein
      concentrations. There is some evidence, based on short-term trials, that
      troglitazone causes only minimal decreases in glycosylated hemoglobin A1C (HbA1C)
      concentrations. Data suggest that troglitazone decreases impaired glucose
      tolerance in nondiabetic obese subjects and leads to a reduction in both systolic
      and diastolic blood pressure in hypertensive type 2 diabetes mellitus patients.
      Troglitazone has a mild adverse effect profile, with rare instances of abnormal
      liver function tests. CONCLUSIONS: Troglitazone appears to be a safe, effective,
      and useful new agent in the treatment of insulin-requiring type 2 diabetes
      mellitus patients, although its HbA1C-lowering effects have been minimal in short
      term trials, and its insulin dosage-reduction activity remains unclear. The Food
      and Drug Administration has also approved its use as monotherapy and in
      combination with sulfonylureas for patients with type 2 diabetes. It may have use
      in the treatment of patients with impaired glucose tolerance, but more clinical
      experience is needed before definitive conclusions can be made. The role of
      troglitazone therapy in diabetes mellitus and impaired glucose intolerance will
      continue to evolve as the results of studies and our clinical experience with
      this agent become available.

PMID- 9533066
TI  - Role of the ketogenic diet in children with intractable seizures.
AB  - OBJECTIVE: To provide a review of the mechanism of action, clinical efficacy,
      adverse effects, drug interactions, and therapeutic considerations associated
      with the use of a ketogenic diet to manage patients with intractable seizures.
      DATA SOURCES: A MEDLINE search from January 1966 to the present and relevant
      articles from journals were reviewed. DATA SYNTHESIS: The ketogenic diet has been
      used as a treatment modality since the early 1920s to control intractable
      seizures. The exact mechanism of action is unknown. Overall, uncontrolled
      clinical studies have reported that approximately one-third of patients with
      intractable seizures have become seizure-free on the ketogenic diet. Common
      adverse events attributed to the diet include dehydration, gastrointestinal
      symptoms, hypoglycemia, as well as carnitine and vitamin deficiencies. Cognitive
      effects, hyperlipidemia, impaired neutrophil function, urolithiasis, optic
      neuropathy, osteoporosis, and protein deficiency may also occur in some patients.
      Carbohydrate content and drug formulation in the selection of medications while
      on the diet are important. Acetazolamide, phenobarbital, and valproic acid have
      been reported to interact with the ketogenic diet. Medications that cause
      carnitine deficiency or influence carbohydrate metabolism should also be used
      with caution. The carbohydrate content of drugs in various therapeutic classes is
      presented to aid in the selection of the most appropriate drug and formulation
      for patients on the ketogenic diet. The success of the diet in controlling
      intractable seizures is related to the patient's close adherence to the diet.
      Minimizing carbohydrate ingestion from medications along with a multidisciplinary
      team approach to the selection and monitoring of the diet are important to the
      success of the ketogenic diet in controlling seizures. CONCLUSIONS: The ketogenic
      diet has shown promising results in controlling intractable seizures; however,
      carefully controlled clinical trials are needed to better assess the efficacy of
      the diet during its use and after discontinuation.

PMID- 9533067
TI  - A primer on continuous renal replacement therapy for critically ill patients.
AB  - OBJECTIVES: To characterize the multiple continuous renal replacement therapy
      (CRRT) techniques available for the management of critically ill adults, and to
      review the indications for and complications of use, principles of drug removal
      during CRRT, drug dosage individualization guidelines, and the influence of CRRT
      on patient outcomes. DATA SOURCES: MEDLINE (January 1981-December 1996) was
      searched for appropriate publications by using terms such as hemofiltration,
      ultrafiltration, hemodialysis, hemodiafiltration, medications, and
      pharmacokinetics; selected articles were cross-referenced. STUDY SELECTION:
      References selected were those considered to enhance the reader's knowledge of
      the principles of CRRT, and to provide adequate therapies on drug disposition.
      DATA SYNTHESIS: CRRTs use filtration/convection and in some cases diffusion to
      treat hemodynamically unstable patients with fluid overload and/or acute renal
      failure. Recent data suggest that positive outcomes may also be attained in
      patients with other medical conditions such as septic shock, multiple organ
      dysfunction syndrome, and hepatic failure. Age, ventilator support, inotropic
      support, reduced urine volume, and elevated serum bilirubin concentrations have
      been associated with poor outcomes. Complications associated with CRRT include
      bleeding due to excessive anticoagulation and line disconnections, fluid and
      electrolyte imbalance, and filter and venous clotting. CRRT can complicate the
      medication regimens of patients for whom it is important to maintain drug plasma
      concentrations within a narrow therapeutic range. Since the physicochemical
      characteristics of a drug and procedure-specific factors can alter drug removal,
      a thorough assessment of all factors needs to be considered before dosage
      regimens are revised. In addition, an algorithm for drug dosing considerations
      based on drug and CRRT characteristics, as well as standard pharmacokinetic
      equations, is proposed. CONCLUSIONS: The use of CRRT has expanded to encompass
      the treatment of disease states other than just acute renal failure. Since there
      is great variability among treatment centers, it is premature to conclude that
      there is enhanced survival in CRRT-treated patients compared with those who
      received conventional hemodialysis. This primer may help clinicians understand
      the need to individualize these therapies and to prospectively optimize the
      pharmacotherapy of their patients receiving CRRT.

PMID- 9533068
TI  - Carvedilol use in heart failure.

PMID- 9533069
TI  - Glutathione in hypersensitivity to trimethoprim/sulfamethoxazole in patients with
      HIV infection.

PMID- 9533070
TI  - The ketogenic diet: the need for a multidisciplinary approach.

PMID- 9533071
TI  - Nonsteroidal antiinflammatory drug-induced hepatitis.

PMID- 9533072
TI  - Significance of a tetracycline and Pepto-Bismol interaction in the management of
      Helicobacter pylori-induced peptic ulcer disease.

PMID- 9533073
TI  - Potential macrolide interaction with verapamil.

PMID- 9533074
TI  - Necrotizing enteritis as a cause of mortality in Laysan albatross, Diomedea
      immutabilis, chicks on Midway Atoll, Hawaii.
AB  - A necropsy survey of Laysan albatross, Diomedea immutabilis, chicks on Midway
      Atoll in June 1993, 1994, and 1995 revealed 54% (21/39), 67% (49/71), and 93%
      (15/16), respectively, to have enteritis as the most severe pathologic finding.
      The lesion was limited to the ileum, ceca, and large intestine. We were unable to
      attribute a single infectious etiology to this lesion. Many birds with enteritis
      also exhibited renal lesions similar to those encountered in chickens
      experimentally deprived of water. We propose that enteritis is a significant
      cause of mortality in Laysan albatross chicks on Midway and that it may be a
      sequela to dehydration. It is likely that the pathology of dehydration in Laysan
      albatross differs from that in chickens largely because of diet.

PMID- 9533075
TI  - Effects of heterophil adaptation on Salmonella enteritidis fecal shedding and egg
      contamination.
AB  - Serial passage of wild-type Salmonella enteritidis (SE) in chicken heterophils
      resulted in decreased shedding of SE in chicken feces and reduced egg
      contamination. When serially heterophil-passaged strains (heterophil-adapted SE
      [HASE]) were given to groups of 12 or more laying hens in drinking water at a
      dose of 10(8) colony-forming units for 3 consecutive days, the inoculum persisted
      in the feces at low frequency for a few days only. Two challenge wild-type
      strains, given in similar manner, persisted in feces at high frequency for 25
      days or longer. The persistence of challenge strains in hens previously exposed
      to HASE was considerably shorter and occurred less frequently than persistence
      and frequency in challenge control hens. HASE strains were not isolated from any
      of 494 eggs laid after exposure to HASE. The challenge strain was isolated from
      15 of 208 eggs (7.2%) after challenge of control hens and never from 461 eggs
      laid after challenge of "vaccinated" hens. I concluded that HASE clones obtained
      by five or more cycles of heterophil phagocytosis were avirulent and immunogenic.

PMID- 9533076
TI  - A dot immunoblotting assay (dot blot ELISA) for early detection of Newcastle
      disease antibodies in chickens.
AB  - An enzyme-linked immunosorbent assay using nitrocellulose blotting membrane (dot
      blot ELISA) was developed for the detection of antibodies against Newcastle
      disease virus (NDV) in chickens. In this method, a nitrocellulose blotting
      membrane was used as the solid phase carrier. NDV antigens were directly bound
      onto the nitrocellulose membrane that was set into a dot blot microfiltration
      apparatus. Efficiency of the assay was evaluated using known positive and
      negative NDV sera obtained from chickens. The ability of the assay to detect
      antibodies 2 days earlier than the standard hemagglutination-inhibition (HI) test
      was demonstrated on sera collected from chickens experimentally infected with
      NDV, La Sota strain.

PMID- 9533077
TI  - Evaluation of different procedures for processing avian air sac lavage fluid.
AB  - Air sac lavage has become a routine diagnostic tool used in pet birds; however,
      cytologic techniques for collection and handling of avian cells have not been
      reported. In this study, directed endoscopy was used to obtain the air sac
      washes. Different factors were compared that might affect final preservation of
      cell morphology, such as centrifugation speed, anticoagulant, storage
      temperature, time to processing, addition of glutaraldehyde to the sample, and
      addition of protein. The goal was to find the processing technique best suited
      for the evaluation of cells from air sac washes. The use of an anticoagulant did
      not influence cell quality. Optimal cell morphology was achieved when the sample
      was centrifuged at a speed of 1000 rpm (89.4 X g) and when prepared in less than
      an hour from the time of collection. Low temperature (5 C) tended to preserve
      cell quality better. The addition of protein (fetal bovine serum) helped to
      preserve cell quality and was of value if the sample storage time was greater
      than 30 min. The addition of glutaraldehyde resulted in a significant reduction
      in cell quality.

PMID- 9533079
TI  - Development of the thoracic air sacs of turkeys with age and rearing conditions.
AB  - Cytology and structure of the thoracic air sac of turkeys were investigated at
      four different ages (26-day embryo, 1 day, 2 wk, and 10 wk old) and two rearing
      conditions (isolation and commercial). Cytology was performed by guided
      fiberoptic endoscopy on the left thoracic air sac of each bird. The right
      thoracic air sac was sampled for light and electron microscopy. Heterophils were
      the most common nonepithelial cell found in air sac fluid. followed by
      macrophages and lymphocytes. Macrophages were most abundant in 1-day-old turkeys
      and turkeys raised in commercial conditions. The epithelium of the air sac
      consisted of squamous and cuboidal cells, with a few ciliated columnar and
      nonciliated columnar cells. Cuboidal cells had similar characteristics to type II
      pneumocytes. The mucociliary system was organized in tracts extended from the
      ostium to the posterior parts of the air sac. The number of ciliated tracts
      decreased with age, and the air sacs of commercial turkeys had a larger
      proportion of ciliated epithelium than did those of isolation birds. The
      epithelium may protect against disease by a structured mucociliary transport
      system, the production of surfactant, and phagocytosis of foreign particles.
      Differences in cytology and structure may reflect the maturation of the immune
      system and/or response to environment.

PMID- 9533078
TI  - Development and validation of a competitive enzyme-linked immunosorbent assay for
      detection of type A influenza antibodies in avian sera.
AB  - Serologic screening of avian sera for group-specific antibodies to type A
      influenza is currently accomplished by using the avian influenza (AI) agar gel
      immunodiffusion (AGID) test. A competitive enzyme-linked immunosorbent assay
      (CELISA) was developed using a baculovirus vector, Autographa californica nuclear
      polyhedrosis virus, expressing the nucleoprotein (NP) gene of A/Ann Arbor/6/60
      influenza virus. The recombinant NP was obtained by inoculation of Spodoptera
      frugiperda (Sf9) insect cells or Trichoplusia ni insect larvae with the
      recombinant baculovirus. A hybridoma cell line producing monoclonal antibody
      against influenza virus A nucleoprotein was used to generate mouse ascitic fluid
      for the CELISA. The nucleoprotein and the monoclonal antibody were used without
      further purification in a CELISA for detection of avian-origin serum antibodies
      to type A influenza. The AI AGID and CELISA tests were compared for sensitivity
      and specificity using 1651 experimental and reference antisera. Samples
      discrepant in AGID and CELISA test results were further evaluated by the AI
      indirect fluorescent antibody (IFA), hemagglutination-inhibition (HI), and
      neuraminidase-inhibition (NI) tests. The results demonstrated a high degree of
      correlation between the AGID and CELISA test results, with the IFA, HI, and NI
      tests offering additional support of CELISA test specificity. The CELISA is a
      rapid, economical, sensitive, and specific serodiagnostic method for screening
      large numbers of avian sera for antibodies to avian influenza virus.

PMID- 9533080
TI  - Airborne horizontal transmission of Salmonella enteritidis in molted laying
      chickens.
AB  - Salmonella enteritidis is currently thought to be transmitted principally through
      contact with infected individuals and ingestion of fecally contaminated
      materials. The present study was undertaken to determine if S. enteritidis could
      be spread in chickens by the airborne route and if induced molting could affect
      this mode of transmission. To test for airborne transmission, hens were placed in
      two rows of cages, the rows separated from each other by 1 m. One row of hens was
      challenged with S. enteritidis, whereas the other row remained unchallenged but
      exposed to the room air. Ventilation delivered within the room provided an even
      air distribution within the area and minimized directional air flow toward any
      set of cages. In Expt. 1, 4 of 12 and 9 to 12 exposed molted hens became infected
      with S. enteritidis after 3 and 8 days of exposure, respectively, compared with 1
      of 12 and 0 of 12 unmolted hens sampled on the same days. Similar S. enteritidis
      levels were detected circulating in the air in the two rooms housing the hens.
      Expts. 2 and 3 examined airborne transmission in molted hens only. In Expt. 2, 2
      of 12 exposed hens became infected with S. enteritidis at 3 days postchallenge,
      and this increased to 12 of 12.1 wk later. In Expt. 3, exposed hens were again
      housed in cages 1 m from challenged hens but were placed in every other cage to
      prevent transmission through contact with hens in adjacent cages. At day 3 post
      challenge, 0 of 12 exposed hens were culture positive for S. enteritidis, and
      this increased to only 3 of 10 positive hens at day 10. Large numbers of S.
      enteritidis shed by the molted challenged hens were recovered from the floors
      beneath the cages. These results indicated that, contrary to the generally held
      beliefs regarding organism spread, airborne transmission of S. enteritidis can
      occur and induced molting can provide the impetus for this event. As was observed
      previously, rapid dissemination of the organism to other members of the flock
      resulted through bird-to-bird contact.

PMID- 9533082
TI  - A survey for Salmonella by drag swabbing manure piles in California egg ranches.
AB  - A cross-sectional study was conducted between August 1995 and November 1996.
      Sixty California egg-producing ranches were chosen at random; 39 ranches agreed
      to participate in the study. The surface of the manure pile in one house on each
      ranch was sampled by drag swabbing. The drag swabs were tested for Salmonella
      using a most probable number procedure that had a detection level of one to five
      Salmonella per drag swab. In 12 ranches (32.4%), the drag swabs were negative for
      Salmonella; the remaining had Salmonella counts in the range of 1 to over 1700
      per swab. Twenty-two different serotypes were found. Salmonella heidelberg and
      Salmonella cerro represented the majority of the typed isolates. Salmonella
      enteritidis (SE) was found on only one ranch. This study found SE to be rare in
      California egg ranches, which implies that these ranches are not a major source
      of S. enteritidis.

PMID- 9533081
TI  - Mucosal and systemic humoral immune response of turkeys after infection and
      reinfection with a Chlamydia psittaci serovar D strain.
AB  - The purpose of this study was to examine the effects of Chlamydia-specific
      antibodies in tears and tracheal washings (IgA and IgG) and sera (IgG) on
      chlamydial excretion during the course of an experimental infection and
      reinfection of turkeys with Chlamydia psittaci. Two groups of turkeys were
      experimentally infected with a serovar D strain of Chlamydia psittaci, either at
      the age of 7 days or at the age of 35 days. A third group was infected at the age
      of 7 days and reinfected with the same strain at 35 days of age. A control group
      consisted of sham infected turkeys. All turkeys were observed daily for clinical
      symptoms. At the age of 49 days, the turkeys were euthanized and examined for
      macroscopic lesions. Following primary infection and reinfection, turkeys were
      equally depressed and dyspneic. Necropsy findings revealed no significant
      differences in the lesions of the birds which received both the prime and
      challenge infection and the birds, which received only a single infection. Anti
      chlamydial antibodies in sera, tears, and tracheal washings were determined by
      IgA and IgG immunoblot assays. A clear local and systemic antibody response
      towards a broad range of chlamydial antigens was already seen 10 to 14 days
      following the experimental infections at both 7 and 35 days of age. In spite of
      the presence of Chlamydia-specific antibodies in tears, tracheal washings, and
      sera, chlamydial excretion was observed in all infected and reinfected turkeys
      throughout the experiment. In most turkeys, this chlamydial excretion was
      detected in three or four tissues sampled at set times, i.e., the conjunctiva,
      nostrils, trachea, and cloaca.

PMID- 9533083
TI  - Cell death in avian tibial dyschondroplasia.
AB  - Tibial dyschondroplasia (TD) is a local defect of growth plates in fast-growing
      poultry where the transitional zone cartilage fails to resorb and persists as an
      avascular plug that prevents endochondral bone formation. We compared the
      differences in the cartilages from normal and TD-affected growth plates using the
      reduction of MTS to assess cartilage viability. Chondrocyte apoptosis was
      determined using biochemical measurement of DNA fragmentation, and in situ
      labeling of nuclei with fluorescein-dUTP using terminal deoxynucleotide
      transferase (TdT)-mediated nick end labeling (TUNEL) of isolated chondrocytes and
      growth plate sections. The TD-affected cartilage showed a significantly lower
      level of MTS reduction and a decrease in trichloroacetic acid (TCA)-precipitable
      DNA content. The TD cartilages had a higher percentage of fragmented DNA, which
      was also evident with agarose gel electrophoresis. A significantly higher number
      of chondrocytes isolated from TD-affected cartilages had condensed morphology,
      shrunken nuclei with little cytoplasm, and were TUNEL positive as identified by
      the incorporation of fluorescein-dUTP into the nuclei. In vivo results similarly
      showed a significant population of chondrocytes in transition zones undergoing
      condensation and apoptosis as determined by in situ TUNEL staining of growth
      plate sections. Normal growth plates, under similar conditions, showed no
      significant apoptosis of chondrocytes from hypertrophic and chondrolyzing zones.
      The condensation and apoptotic cell death may be responsible for the reduction of
      growth plate viability as well as the reduction in DNA content and increased DNA
      fragmentation. While the cause of the pathogenesis of TD is unknown, it appears
      that the aberrant death of chondrocytes in hypertrophic regions of growth plates
      may be responsible for the accumulation of cartilage and the arrest of
      endochondral bone formation.

PMID- 9533084
TI  - Antigenic and immunogenic properties of baculovirus-expressed infectious bursal
      disease viral proteins.
AB  - Genomic segment A of the variant Md infectious bursal disease virus (IBDV) was
      amplified by reverse transcriptase/polymerase chain reaction, cloned, and
      expressed in the baculovirus expression system. Three different baculovirus
      recombinants expressing the genes encoding VP2, VP2/VP4, and the complete
      polyprotein (VP2/VP4/VP3) were prepared. The three antigens were used in separate
      enzyme-linked immunosorbent assays, and each detected antibodies against the
      variant IBDV strains Md, Del-A, Del-E, and GLS and the classic IBDV strain D78
      throughout a 14-wk period following vaccination. Eight-week-old specific-pathogen
      free (SPF) chickens were inoculated subcutaneously using the VP2/VP4 or
      VP2/VP4/VP3 baculovirus recombinant or wild-type baculovirus-infected insect cell
      lysates. Virus-neutralizing antibodies were detected in the VP2/VP4 and
      VP2/VP4/VP3 baculovirus-inoculated birds at 13 days postinoculation (PI) and at
      43 days PI when titrated against Md IBDV. No virus-neutralizing antibody titer
      was observed in the negative controls or wild-type baculovirus-inoculated birds.
      One-week-old SPF chickens were inoculated with the VP2, VP2/VP4/VP3 baculovirus
      recombinants or wild-type baculovirus-infected insect cell lysates. The birds
      were boosted 2 wk later and challenged at 4 wk of age with 0.5 ml/bird classic
      STC IBDV (10(2) median embryo infective dose [EID50]/ml) or variant Md IBDV
      (10(5) EID50/ml) via the oral/nasal route. The VP2 and VP2/VP4/VP3 baculovirus
      inoculated birds were partially protected against challenge with the classic STC
      IBDV. The birds were protected against clinical disease and death but not bursal
      damage, whereas the wild-type baculovirus-inoculated birds exhibited clinical
      signs of disease, 13% mortality, and bursal damage. When challenged with the
      variant Md IBDV, neither the VP2, VP2/VP4/VP3 baculovirus recombinants nor the
      wild-type baculovirus elicited protection against bursal damage and atrophy.

PMID- 9533085
TI  - Detection and classification of infectious bronchitis viruses isolated in Korea
      by dot-immunoblotting assay using monoclonal antibodies.
AB  - Dot-immunoblotting assay (DIA) using five monoclonal antibodies (MAbs) to
      infectious bronchitis virus (IBV) was used to detect and classify the viruses
      propagated in embryonated chicken eggs. Using a group-specific MAb 3F5, 10
      reference strains and 12 Korean isolates of IBV were successfully detected by
      DIA, and the lowest virus titer of IBV detected by DIA was approximately less
      than 10(3.8) mean embryo infective dose/ml. For evaluating the diagnostic
      efficiency, DIA was compared with the conventional infectious bronchitis (IB)
      diagnostic method. IBV antigens in allantoic fluid from embryonated eggs
      inoculated with IB-suspected field samples were specifically detected by DIA
      within only one or two egg passages, whereas the conventional embryonated egg
      inoculation method required four to seven egg passages for confirming IBV
      infection. These results indicated that DIA could significantly reduce time and
      cost for IB diagnosis. For examining the possibility of classifying IBV by DIA,
      four strain-specific MAbs, 3A4, 2A3, 6F7, and 2C6, were used. According to the
      MAb reacting patterns to the IBV antigens, the 10 IBV reference strains were
      classified into six groups; seven strains belonged to three different groups, and
      the other three strains each belonged to an individual group. In the case of 12
      Korean isolates of IBV, they were classified in six groups. Among the six groups,
      the MAb reacting patterns of three groups matched those of the IBV reference
      strains, but the others did not. These data suggest that at least three variant
      serotypes of IBV exist in Korea.

PMID- 9533086
TI  - DNA fingerprinting of Riemerella anatipestifer.
AB  - Seventeen restriction endonucleases were evaluated for use in DNA fingerprinting
      of Riemerella anatipestifer. Digestion of chromosomal DNA with either HinfI or
      DdeI restriction endonuclease, followed by submarine electrophoresis in agarose
      and staining with ethidium bromide, resulted in DNA fingerprint profiles that
      could be easily resolved. HinfI produced readable fingerprint patterns in the 2.7
      20-kb range and was used to distinguish DNA fingerprint profiles among 89 strains
      of R. anatipestifer representing isolates from various avian species in the
      United States, the United Kingdom, Australia, Canada, Germany, and Israel. A
      total of 52 distinct DNA fingerprint profiles were found.

PMID- 9533087
TI  - The occurrence of ambient temperature-regulated adhesins, curli, and the
      temperature-sensitive hemagglutinin tsh among avian Escherichia coli.
AB  - Escherichia coli establishes a secondary respiratory tract infection in birds
      following inhalation of contaminated dust and litter particles. Escherichia coli
      express adhesins under conditions reflective of the ambient temperatures present
      in poultry houses. These microbial adhesins allow E. coli to attach to cell types
      that it initially encounters in the respiratory tract. Ambient temperature
      regulated adhesins represent a new class of bacterial hemagglutinins that include
      pili and the thin, aggregative, flexible filaments known as "curli." This study
      examines the occurrence of the ambient temperature-regulated adhesins, curli
      (crl, csgA), and an avian-specific, temperature-sensitive hemagglutinin, tsh,
      among avian and mammalian E. coli isolates. The avian hemagglutinin gene tsh was
      present in approximately 46% of clinical avian E. coli isolates. This gene was
      not detected among commensal E. coli isolated from healthy broiler chickens.
      Unlike tsh, curli genes were ubiquitous among E. coli. However, curli were
      observed in only half of the avian E. coli examined by electron microscopy. Curli
      were not present among several nonavian E. coli positive for crl and csgA.
      Approximately 25% of avian E. coli isolates agglutinated chicken erythrocytes
      when bacteria were grown at room temperature. Hemagglutination was not specific
      to E. coli isolated from poultry. Presence of either tsh or curli genes was not
      indicative of an isolate's ability to agglutinate chicken red blood cells. No
      discernible structures were observed mediating attachment of the bacteria to
      chicken red blood cells. An additional avian-specific hemagglutinin appears to be
      present among avian E. coli.

PMID- 9533088
TI  - Detection of Eimeria acervulina using the polymerase chain reaction.
AB  - A polymerase chain reaction (PCR)-based assay was developed for the detection of
      Eimeria acervulina. Primers were designed to amplify a fragment of the
      EASZ240/160 sporozoite antigen gene. The PCR assay detected as few as 10 E.
      acervulina oocysts in a mixed population containing a total of 10(6) oocysts. No
      nonspecific reaction was observed with any other species of avian Eimeria known
      to occur in Australia. PCR products from genomic DNA were 237 bp larger than
      predicted from previously reported cDNA sequences. Sequencing of the product
      revealed the presence of a probable intron. This work demonstrates the potential
      of PCR-based assays for identification and detection of avian Eimeria. Potential
      uses include identification of minor species present in mixed infections and
      quality control in the production of live vaccines.

PMID- 9533089
TI  - Relationship between the immunosuppressive potential and the pathotype of Marek's
      disease virus isolates.
AB  - Isolates of Marek's disease virus (MDV) representing three pathotypes of
      differing virulence were compared for relative immunosuppressive properties in
      genetically susceptible P2a-strain and genetically resistant N2a-strain chickens.
      Criteria of immunosuppression were 1) persistence of early cytolytic infection
      (i.e., a delay or failure to enter latency) in lymphoid organs, 2) atrophy of the
      bursa of Fabricius and thymus as measured by organ weight proportional to body
      weight at 8 and 14 days postinfection (DPI), and 3) histopathologic evidence of
      necrosis and atrophy in lymphoid organs. No significant differences in infection
      level were observed among the pathotypes during the early (4-5 DPI) period of
      infection. However, the extent of persistent cytolytic infection at 7-8 DPI,
      based on numbers of tissues positive and mean scores in immunofluorescence tests,
      was greater (P < 0.05) for three isolates (RK1, 584A, 648A) in the highest
      virulence pathotype (very virulent-plus MDV [vv + MDV]) than for two isolates
      (JM16, GA5) in a lower virulence (virulent MDV [vMDV]) pathotype. Results from
      two isolates (RB1B, Md5) classified in the intermediate very virulent pathotype
      (very virulent MDV [vvMDV]) fell between those from the other two pathotypes.
      Similarly, there was a stepwise effect of viral pathotype in which the vv + MDV
      isolates caused the most severe damage to lymphoid organs in terms of atrophy
      (relative organ weights) and histopathologic changes. Organs from chickens
      infected with vv + MDVs showed little recovery between 8 and 14 DPI. The vMDV
      isolates caused the least severe damage, and lymphoid organs showed a significant
      return toward normal by 14 DPI; vvMDV isolates induced intermediate degrees of
      atrophy and recovery. The same pattern of relationship between virulence
      pathotype and degree of bursal and thymic atrophy was also observed in
      genetically resistant N2a chickens. These results suggest that the degree of
      immunosuppression is linked to virulence and that a simple measure of atrophic
      changes (relative organ weights) in the bursa of Fabricius and thymus might be
      useful in determining the pathotype classification of new MDV isolates. The basis
      for differences in immunosuppressive potential of MDV isolates needs further
      clarification.

PMID- 9533090
TI  - Detection of goose and Muscovy duck parvoviruses using polymerase chain reaction
      restriction enzyme fragment length polymorphism analysis.
AB  - By using primers (AL18F2 and AL18R2) designed from goose parvovirus (GPV) strain
      IHC, an 806-bp band was amplified by polymerase chain reaction (PCR) from all of
      17 samples from Thailand. Specificity to GPV was confirmed by Southern
      hybridization. With restriction enzyme digestion of the PCR products, two
      isolates differed from the other 15 isolates by the absence of restriction sites
      for HincII and BglII and the presence of EcoR1 site. Nucleotide sequence analysis
      of the PCR products from the different groups revealed that one group is GPV and
      the other group is Muscovy duck parvovirus (MDPV). Thus restriction enzyme
      fragment length polymorphism analysis of the PCR products could be used to
      distinguish GPV and MDPV. The data showed that GPV and MDPV are present in
      Thailand.

PMID- 9533091
TI  - Improvement of poult performance following Bordetella avium challenge by
      administration of a novel oxy-halogen formulation.
AB  - The ability of a novel oxy-halogen formulation (OHF) to alter the development of
      bordetellosis (turkey coryza) in large white turkey poults was assessed.
      Bordetella avium (BA)-infected (1-day-of-age) and noninfected control poults
      received 0, 0.008%, or 0.016% of an OHF continuously in the drinking water. At 4,
      7, 10, 14, and 17 days of age, reisolation of BA from infected poults was
      attempted. Infected poults receiving 0.016% OHF exhibited significantly lower
      cumulative BA reisolation rates (90%) when compared with infected poults
      receiving 0 (96.7%) or 0.008% OHF (100%). At 7, 14, and 17 days of age, infected
      poults in the OHF-treated groups were significantly heavier than those BA
      challenged poults receiving control water. Feed utilization was significantly
      improved from hatch to 7 days of age in BA-infected poults receiving OHF when
      compared with infected poults receiving control water. Clinical symptoms were
      severe only in untreated, infected poults and were mild or absent in all others.
      Damage to the tracheal epithelium, as measured by scanning electron microscopy,
      paralleled the clinical signs. Tracheal epithelial damage was virtually
      eliminated by OHF administration in infected poults. These results suggest that
      OHF treatment ameliorates many of the symptoms frequently associated with
      bordetellosis in young turkeys.

PMID- 9533092
TI  - Mutation rate of avian intestinal coliform bacteria when pressured with
      fluoroquinolones.
AB  - The purpose of this study was to determine the rate at which resistance developed
      in avian coliform bacteria when exposed to nalidixic acid, sarafloxacin, or
      enrofloxacin. In in vitro studies, the rates of mutation of avian isolates of
      Escherichia coli and Salmonella were determined following nalidixic acid,
      sarafloxacin, or enrofloxacin pressure. The rates of mutation were similar for
      nalidixic acid and sarafloxacin, whereas a lower rate of mutation was seen after
      enrofloxacin pressure. In in vivo studies, the quinolones were administered in
      the drinking water to broiler chickens at a concentration of 40 ppm for five
      consecutive days. Samples of feces were inoculated onto appropriate media and the
      frequency of resistance was determined. The frequency rates of resistance to
      nalidixic acid and sarafloxacin were similar. Enrofloxacin-medicated birds did
      not develop enrofloxacin-resistant coliform bacteria. The in vitro and in vivo
      data appear to correlate.

PMID- 9533093
TI  - Ornithobacterium rhinotracheale infection in turkeys: experimental reproduction
      of the disease.
AB  - This report details the first experimental production of clinical disease,
      mortality, and pathology resembling that of field infections by using
      Ornithobacterium rhinotracheale alone. Twenty-two-week-old male turkeys were
      exposed to O. rhinotracheale or lung homogenate from O. rhinotracheale-infected
      turkeys. Within 24 hr after inoculation, turkeys given O. rhinotracheale or lung
      homogenate intratracheally were depressed and coughing and had decreased feed
      intake. By 48 hr, several birds were coughing blood and ultimately died. Grossly,
      the lungs were reddened, wet, and heavy, failed to collapse, and were covered by
      tenacious tan-to-white exudate. Microscopically, the parabronchi and air
      capillaries were filled with fibrin, heterophils, macrophages, and small numbers
      of gram-negative bacteria. The pleura was often covered by a thick layer of
      fibrin, heterophils, and macrophages. Turkeys that survived to day 7
      postinoculation had severe, subacute pneumonia. Ornithobacterium rhinotracheale
      was recovered from the lungs of most birds with pneumonia and was also cultured
      from the air sacs, sinuses, tracheas, spleens, and livers. All turkeys inoculated
      with O. rhinotracheale developed antibodies to O. rhinotracheale detectable by
      the serum plate agglutination test.

PMID- 9533094
TI  - Effect of tibial dyschondroplasia on broiler growth and cancellous bone
      mechanical properties.
AB  - The increased incidence of leg abnormalities, particularly tibial
      dyschondroplasia, in chickens could be related to changes in tibiotarsal
      cancellous bone properties. To explore this hypothesis, the relationship between
      lesion occurrence and various tibiotarsal growth parameters, and subchondral bone
      strength characteristics was investigated. A higher elastic modulus, meaning the
      cancellous bone was more rigid, was seen for tibiotarsal cancellous bone with
      lesions. Microfractures in cancellous bone, particularly in the medial growth
      plate region, may lead to overall bone conformation changes and therefore to
      lameness.

PMID- 9533095
TI  - Recommended storage and resuscitation conditions for the MDCC-MSB1 cell line.
AB  - Storage and resuscitation of MDCC-MSB1 cells, most commonly used for the
      propagation of chicken anemia virus was studied. Cells were frozen slowly in RPMI
      medium 1640 with 10% or 20% fetal bovine serum and 20% dimethyl sulfoxide, held
      at -70 C overnight, and placed into liquid nitrogen the next day. After 1 mo, 91%
      to 100% resuscitation rates were obtained, while cells that were frozen fast
      (directly transferred into liquid nitrogen) could not be resuscitated.

PMID- 9533096
TI  - Efficacy of combined killed-in-oil emulsion and live Newcastle disease vaccines
      in chickens.
AB  - Following the introduction of routine vaccination regimes with different types of
      Newcastle disease (ND) vaccines, the incidence of velogenic viscerotropic
      Newcastle disease (VVND) in commercial poultry worldwide has declined
      dramatically. Unfortunately, these vaccination regimes are not feasible in free
      range and backyard systems of poultry production practiced in many developing
      countries. In this study, we sought to develop a single vaccination regime in
      chickens with ND vaccines to elicit a long-lasting high level of ND virus (NDV)
      antibodies adequate to protect chickens against ND. The level of antibody
      response, as measured by the hemagglutination-inhibition (HI) test, and the
      degree of protection against the virulent strain of NDV were studied in chickens
      immunized with different vaccines. The vaccines used were: killed-in-oil emulsion
      (subcutaneous; s.c.) plus live virus (oculanasal; o.n.), given concurrently;
      experimental vaccine (s.c.) plus live virus (o.n.), given concurrently; killed-in
      oil (s.c.); experimental vaccine prepared by homogenizing commercial live vaccine
      and oil emulsion (s.c.); and live virus (o.n.). The results obtained in this
      study indicate that concurrent administration of oil emulsion and live NDV
      vaccines induced the best antibody response, but there was no significant
      difference in protection among the vaccinated groups.

PMID- 9533097
TI  - Endoscopic gross anatomy findings of the thoracic air sac of the turkey.
AB  - The gross anatomy of the cranial thoracic air sacs was studied in the live turkey
      with a fiber-optic endoscope fitted with a video system. Thirty-five out of 39
      (89.7%) of the turkeys had paired single thoracic air sacs with two ostia. The
      other 10.3% of the turkeys had paired cranial and caudal thoracic air sacs, each
      with a single ostium. The air flow pattern through the common thoracic air sac
      with two ostia is unknown. Furthermore, 42.3% of the turkeys with a single
      thoracic air sac had an invagination arising from the floor of the air sac that
      partially divided the single thoracic air sac creating a blind-ended sac. The
      blind sac formed by the invagination may trap small inhaled particulate matter.

PMID- 9533098
TI  - Antibodies to alphavirus, flavivirus, and bunyavirus arboviruses in house
      sparrows (Passer domesticus) and tree sparrows (P. montanus) in Poland.
AB  - Sparrows from central Poland were examined by a hemagglutination-inhibition test
      (titer > or = 20) for the presence of antibodies to arboviruses, between 1995 and
      1996. In house sparrows (Passer domesticus) (n = 179), antibodies to Sindbis,
      West Nile, tick-borne encephalitis, Tahyna, and Calovo viruses were detected at
      seroprevalences of 1.1%, 2.8%, 1.1%, 2.8%, and 1.1%, respectively. In tree
      sparrows (P. montanus) (n = 33), antibodies to the Sindbis, West Nile, and Tahyna
      viruses were detected at seroprevalences of 9.1%, 12.1%, and 3.0%, respectively.

PMID- 9533099
TI  - Serum and egg yolk IgG antibody titers from laying chickens vaccinated with
      Pasteurella multocida.
AB  - Through determining the serum and egg yolk antibody titers in immunized laying
      hens to Pasteurella multocida regularly, the growth-decline trend of the egg yolk
      antibody levels was found to be similar to that of the serum antibody levels (r =
      0.94), but the growth and decline of the egg yolk antibody seemed to be delayed 3
      6 days compared with that of the serum antibody, and the egg yolk antibody titers
      were generally lower than those of the serum antibody (P < 0.01). Serum and egg
      yolk antibody levels declined 3 and 6 days, respectively, after booster
      immunizations. The higher the antibody levels were before booster immunization,
      the more they declined.

PMID- 9533100
TI  - Pasteurella challenge and ELISA serology evaluation of broiler breeders
      vaccinated with live cholera vaccine.
AB  - Broiler breeder pullets were vaccinated against fowl cholera at 10 and 20 wk of
      age using a live PM-1 Pasteurella multocida vaccine administered by wing web
      stick. Antibody production for P. multocida was measured at vaccination and at 1
      4-wk intervals following vaccination by enzyme-linked immunosorbent assay. Groups
      of vaccinated birds were challenged at 23 and 32 wk of age. Two doses of a live
      PM-1 P. multocida vaccine protected broiler breeder hens against virulent
      challenge up to 32 wk of age when measured antibody levels had a range of 1951
      4346 and a geometric titer of 3000.

PMID- 9533101
TI  - Colonization of the chicken trachea by an avirulent avian Escherichia coli
      transformed with plasmid pHK11.
AB  - Recombinant plasmid pHK11 was transformed into an avirulent, wild-type avian
      Escherichia coli (E. coli Av) in order to study the plasmid's effect on
      colonization of the chicken trachea. The transformant (E. coli Av + pHK11)
      produced colicin V (ColV), had type F1 fimbriae, and was motile. The E. coli Av
      recipient possessed type F1 fimbriae but was nonmotile; it did not produce ColV.
      Four-day-old chicks were inoculated in the trachea with 100 microliters of an
      overnight culture (approximately 10(8) colony-forming units) of E. coli Av, E.
      coli Av + pHK11, or sterile brain-heart infusion (BHI) broth. A group of
      uninoculated chicks was also included. Samples of the trachea were taken on days
      4 and 10 postinoculation and compared histologically and bacteriologically. Birds
      inoculated with E. coli Av + pHK11 had enhanced tracheal colonization and showed
      increased histologic changes as compared with those inoculated with E. coli Av or
      BHI broth or uninoculated controls. These results indicate that production of
      ColV and motility enhance the colonization of the trachea and may be involved in
      the cause of pathologic lesions.

PMID- 9533102
TI  - Effects of biogenic amines in broiler chickens.
AB  - Biogenic amines in spoiled animal by-product feeds have been implicated in
      causing poor performance and intestinal lesions in broilers. This study was
      designed to determine if biogenic amines, at the concentrations found in animal
      by-product meals, would reduce performance in broilers or cause lesions. Twelve
      treatments were used in a 2 x 6 factorial arrangement with the main effects being
      either a corn-soybean meal diet or a corn-soybean meal diet with 10% animal by
      products added and either no amines added or added levels of phenylethylamine
      (4.8 mg/kg), putrescine (49 mg/kg), cadaverine (107 mg/kg), histamine (131
      mg/kg), or a combination of all these amines. Levels of biogenic amines used in
      this study simulated those found in areas with reported problems attributed to
      biogenic amines. Broilers were monitored for performance, gross lesions, and
      histologic evidence of lesions at 2, 4, and 6 wk. No consistent effects were
      observed on performance, and by the conclusion of the trial, no statistical
      differences were noted in the performance of any of the treatments. No gross
      lesions were observed on a consistent basis in any of the treatments.
      Histopathology was likewise unremarkable. On the basis of this study, it would
      appear that these four biogenic amines, at levels detected in the United States,
      do not pose a serious health concern for the broiler industry.

PMID- 9533103
TI  - Subacute to chronic fowl cholera in a flock of Pharaoh breeder quail.
AB  - A total of 1300 birds in flock of breeder Pharaoh quail (Coturinix coturnix)
      experienced a moderate rate of mortality (13%) during a 7-day period. Clinical
      signs included depression, ruffled feathers, prostration, lameness, inapetence,
      diarrhea, and periorbital sinus swelling with mucoid discharge and lameness.
      Gross lesions observed in dead quail were emaciation, carcass congestion, mild
      hepatomegaly with green discoloration, congested intestinal mucosa, caseous
      purulent arthritis-osteomyelitis, and thickened crop mucosal epithelium.
      Histopathologic examination revealed mild hepatic amyloidosis, proliferative
      parabronchitis, splenic reticular cell hyperplasia, thymic cortical atrophy,
      subacute bacterial osteomyelitis, periarthritis, and crop mycosis. Pasteurella
      multocida was isolated from the joints of these birds and the isolates were
      serotype 3 x 4. These findings suggest that Pharaoh quail are susceptible to P.
      multocida and are likely to develop subacute to chronic fowl cholera.

PMID- 9533104
TI  - Systemic amyloidosis in laying Japanese quail.
AB  - Systemic amyloidosis was seen in laying Japanese quail in a flock of a farm
      rearing 95,000 birds. The clinical signs included decreased egg production,
      anorexia, white diarrhea, and subcutaneous abscesses of the head. Histologically,
      amyloid deposited predominantly in the spleen and liver. In addition, there were
      lesser degrees of amyloidosis in other organs (pancreas, kidney, heart, lung,
      gastrointestinal tract). Amyloid stained positively with Congo red and thioflavin
      T. Immunohistochemically, amyloid substance stained positively against amyloid A
      protein, but not with amyloid protein derived from light chains of
      immunoglobulins, transthyretin of familiar amyloid polyneuropathy, amyloid
      protein of dermal amyloidosis, nor amyloid P component. Ultrastructurally,
      amyloid substance consisted of many nonbranching amyloid fibrils about 10 nm in
      diameter.

PMID- 9533105
TI  - Sodium sesquicarbonate toxicity in broiler chickens.
AB  - A case of feed misformulation resulted in the addition of sodium sesquicarbonate
      (SSC) into broiler chicken feed. SSC is a buffering agent used in the manufacture
      of high urea ruminant feeds that were also produced in this feed mill. Within 2
      days of receipt of the tainted broiler feed on the farm, chickens were exhibiting
      polydypsia and wet droppings and had increased levels of mortality. The
      postmortem lesions were dehydration, fluid-filled intestines, swollen, pale
      kidneys, and visceral urate deposits. Histopathology of the kidneys revealed
      dilated tubules with a giant cell response, loss of tubular epithelium, and a few
      needlelike crystals. The mortality within 4 days of exposure in three severely
      affected houses reached 17%. An analysis of the feed revealed sodium levels
      ranging from 2.59% to 4.88%, with chloride levels of 0.24%-0.40%. Ten percent of
      the ration was thought to be SSC that contains 36% sodium. To determine if the
      presence of the SSC caused the problems observed, a controlled study was
      undertaken. One hundred fifty 3-wk-old broilers were evenly distributed into
      three floor pens. One group was fed a normal grower ration, a second group was
      fed a ration containing 5% SSC, and a third group received a ration with 10% SSC.
      Mortality, packed cell volumes (PCV), total serum proteins, and histopathology of
      the kidneys were determined. The 10% SSC group had a 6% mortality. Dehydration
      was evident by elevated PCV within 1 day of ingestion of either ration containing
      SSC. Microscopic lesions in the kidney were more severe in chickens ingesting SSC
      when compared with control groups.

PMID- 9533106
TI  - Isolation and identification of Ornithobacterium rhinotracheale from commercial
      turkey flocks in the upper midwest.
AB  - Increased death loss was seen in a flock of 22-wk-old tom turkeys. The
      predominant postmortem lesion was fibrinopurulent pneumonia and pleuritis. Within
      5 wk, turkey flocks on 17 other farms developed similar problems. All affected
      flocks during the 5-wk period were between 14 and 22 wk of age, and the severity
      of clinical signs and the degree of mortality increased with age.
      Ornithobacterium rhinotracheale was isolated in pure culture from affected lungs.
      Further investigation by tracheal swab culture of 261 flocks between 5 and 7 wk
      of age resulted in detection of O. rhinotracheale in 43% of the flocks.

PMID- 9533108
TI  - Induction of tirilazad clearance by phenytoin.
AB  - Tirilazad is a membrane lipid peroxidation inhibitor being studied for the
      management of subarachnoid hemorrhage; phenytoin is used for seizure prophylaxis
      in the same disorder. The induction of tirilazad clearance by phenytoin was
      assessed in 12 volunteers (6 male, 6 female). Subjects received phenytoin orally
      every 8 h for 7 days (200 mg for nine doses and 100 mg for 13 doses) in one phase
      of a crossover study. In both study phases, 1.5 mg kg-1 tirilazad mesylate was
      administered by i.v. infusion every 6 h for 29 doses. Tirilazad mesylate and U
      89678 (an active metabolite) in plasma were quantified by HPLC. After the final
      dose, tirilazad clearance was increased by 91.8% in subjects receiving phenytoin
      + tirilazad versus tirilazad alone. AUC0-6 for U-89678 after the last tirilazad
      dose was reduced by 93.1% by concomitant phenytoin. These effects were
      statistically significant. The time course of induction was consistent with that
      of phenytoin's effect on the ratio of urinary 6 beta-hydroxycortisol to cortisol,
      a measure of hepatic CYP3A activity. The results show that phenytoin induces
      metabolism of tirilazad and U-89678 in healthy subjects and that, under these
      conditions, tirilazad clearance approaches liver blood flow.

PMID- 9533107
TI  - Pharmacokinetic changes of M1, M2, M3 and M4 after intravenous administration of
      a new anthracycline, DA-125, to rats pretreated with phenobarbital, 3
      methylcholanthrene, chloramphenicol, or SKF-525A.
AB  - The pharmacokinetics of M1-M4, the metabolites of a new anthracycline
      antineoplastic agent, DA-125, were compared after intravenous (i.v.)
      administration of DA-125, 15 mg kg-1, to rats pretreated with enzyme inducers,
      such as phenobarbital (PBT, n = 14) and 3-methylcholanthrene (MCT, n = 15), or
      enzyme inhibitors, such as SKF-525A (SKT, n = 11) and chloramphenicol (CMT, n =
      15), and to their control rats (n = 15 for PBC, CMC or SKC, and n = 11 for MCC).
      After i.v. administration of DA-125, the plasma concentrations of both M1 and M2
      declined slowly from 1 to 2 h onwards to 8 h in all groups of rats due to the
      continuous formation of M2 from M1. The AUC0-8 h of M1 (47.1 versus 7.85
      micrograms min mL-1) and M2 (20.7 versus 44.3 micrograms min mL-1) decreased
      significantly in the PBT group compared to those in the PBC group. However, the
      corresponding value of only M1 (74.6 versus 89.9 micrograms min mL-1) decreased
      significantly in the MCT group. The above data indicate that metabolism of M1 is
      increased by pretreatment with both PB and 3-MC, and that of M2 with PB, but not
      with 3-MC. The AUC0-8 h of both M1 (126 versus 78.5 micrograms min mL-1) and M2
      (69.2 versus 44.3 micrograms min mL-1) increased significantly in the SKT group
      compared to the SKC group. However, the corresponding values were not
      significantly different between CMC and CMT groups. The above data indicate that
      the metabolism of both M1 and M2 is inhibited by pretreatment with SKF-525A, but
      not with CM.

PMID- 9533109
TI  - No effect of chloroquine on theophylline pharmacokinetics in the rat.
AB  - The immediate and delayed effects of chloroquine on theophylline kinetics were
      investigated in rats pretreated with chloroquine diphosphate (45 mg kg-1) or
      saline intraperitoneally. One hour or 4 days after chloroquine, theophylline (10
      mg kg-1) was administered intravenously. Compared with the control animals
      pretreated with saline, the disposition parameters of theophylline was not
      altered after pretreatment with chloroquine. Chloroquine did not affect the in
      vivo metabolism of theophylline in the laboratory rat. A possible decrease in
      theophylline's volume of distribution at 4 days, but not immediately, after
      administration of chloroquine was suggested, although this just failed to achieve
      statistical significance (p = 0.055). Being marginal, it is unlikely to be of
      clinical concern. It is concluded that, judged from these animal data, there is
      no evidence of a drug-drug pharmacokinetic interaction for the combination of
      chloroquine and theophylline.

PMID- 9533110
TI  - Pharmacokinetics of a non-narcotic analgesic, DA-5018, in rats.
AB  - The pharmacokinetics of a non-narcotic analgesic, DA-5018, were compared after
      single intravenous (i.v.), subcutaneous (s.c.), and oral administrations, and
      after multiple (seven consecutive days) s.c. administration to rats. After i.v.
      administration of DA-5018, 1, 2, and 5 mg kg-1, the pharmacokinetic parameters of
      DA-5018 were independent of the dose ranges studied. After oral administration of
      DA-5018, absorption of the drug from gastrointestinal (GI) tract was fast, but
      the extent of absolute bioavailability (F) was low; the values were 23.2, 23.0,
      and 27.3% for 2, 5, and 10 mg kg-1, respectively. After single s.c.
      administration of DA-5018, absorption of the drug from the injected site was fast
      and the extent of absorption was fairly good; the F values were 74.5 and 71.8%
      for 2 and 5 mg kg-1, respectively. The lower F values after oral administration
      of DA-5018 to rats could be due to degradation of the drug in rat GI tract and/or
      considerable first-pass effect. After i.v., oral, and s.c. administration of DA
      5018, the drug had a strong affinity to the rat tissues studied as reflected in
      the greater-than-unity tissue to plasma ratio. After i.v., oral, and s.c.
      administration of the drug, the biliary and urinary excretion of unchanged DA
      5018 were negligible. There was no significant difference in the pharmacokinetics
      or tissue distribution of DA-5018 between single and multiple s.c. administration
      of the drug, 5 mg kg-1, to rats, indicating that there could be no tissue
      accumulation of the drug after multiple s.c. administration of the drug to rats.

PMID- 9533111
TI  - Pharmacokinetics and haemodynamic effect of deacetyl diltiazem (M1) in rabbits
      after a single intravenous administration.
AB  - Deacetyl diltiazem (M1) is a major metabolite of the widely used calcium
      antagonist diltiazem (DTZ). In order to study the pharmacokinetic and
      haemodynamic effects of this metabolite, M1 was administered as a single 5 mg kg
      1 dose intravenously (i.v.) to New Zealand white rabbits (n = 5) via a marginal
      ear vein. Blood samples, blood pressure (SBP and DBP), and heart rate (HR)
      recordings were obtained from each rabbit up to 8 h, and urine samples for 48 h
      post-dose. Plasma concentrations of M1 and its metabolites were determined by
      HPLC. The results showed that the only quantifiable basic metabolite in the
      plasma was deacetyl N-monodesmethyl DTZ (M2). The t1/2 and AUC of M1 and M2 were
      2.1 +/- 0.5 and 3.0 +/- 1.1 h, and 1300 +/- 200 and 240 +/- 37 ng h mL-1,
      respectively. The Cl and Clr of M1 were 60 +/- 10 and 0.81 +/- 0.63 mL min-1 kg
      1, respectively. M1 significantly decreased blood pressure (SBP and DBP) for up
      to 1 h post-dose (p < 0.05), but had no significant effect on the heart rate (P >
      0.05). The Emax and EC50 as estimated by the inhibitory sigmoidal Emax model were
      20 +/- 18% 620 +/- 310 ng mL-1, respectively for SBP; 20 +/- 8.3% and 420 +/- 160
      ng mL-1 for DBP.

PMID- 9533112
TI  - Catalepsy induced by calcium channel blockers in mice.
AB  - It is known that calcium channel blockers induce Parkinsonism. In this study,
      amlodipine-, diltiazem-, and verapamil-induced catalepsy was investigated in
      mice. All of these three calcium channel blockers induced catalepsy. Dopamine D1,
      D2, and mACh receptor occupancies were estimated under the same conditions, and
      the affinities of these drugs for each receptor were also estimated in vitro.
      Intensity of catalepsy was predicted by dopamine D1, D2, and mACh receptor
      occupancies with the dynamic model which had already been constructed and was
      compared with the observed values. The predicted and the observed values were
      comparable (r = 0.98, p < 0.001). In conclusion, the dynamic model considering
      D1, and D2, and mACh receptor occupancy may be useful for quantitative prediction
      of drug-induced catalepsy.

PMID- 9533113
TI  - Pharmacokinetics and tissue disposition of danofloxacin in sheep.
AB  - The plasma pharmacokinetics of danofloxacin administered at 1.25 mg kg-1 body
      weight by the intravenous and intramuscular routes were determined in sheep.
      Tissue distribution was also determined following administration by the
      intramuscular route at 1.25 mg kg-1 body weight. Danofloxacin had a large volume
      of distribution at steady state (Vdss) of 2.76 +/- 0.16 h (mean +/- S.E.M.) L kg
      1, an elimination half-life (t1/2 beta) of 3.35 +/- 0.23 h, and a body clearance
      (C1) of 0.63 +/- 0.04 L kg-1 h-1. Following intramuscular administration it
      achieved a maximum concentration (Cmax) of 0.32 +/- 0.02 microgram mL-1 at 1.23
      +/- 0.34 h (tmax) and had a mean residence time (MRT) of 5.45 +/- 0.19 h.
      Danofloxacin had an absolute bioavailability (F) of 95.71 +/- 4.41% and a mean
      absorption time (MAT) of 0.81 +/- 0.20 h following intramuscular administration.
      Mean plasma concentrations of > 0.06 microgram mL-1 were maintained for more than
      8 h following intravenous and intramuscular administration. Following
      intramuscular administration highest concentrations were measured in plasma (0.43
      +/- 0.04 microgram mL-1), lung (1.51 +/- 0.18 micrograms g-1), and interdigital
      skin (0.64 +/- 0.18 microgram g-1) at 1 h, duodenal contents (0.81 +/- 0.40
      microgram mL-1), lymph nodes (4.61 +/- 0.35 micrograms g-1), and brain (0.06 +/-
      0.00 microgram mL-1) at 2 h, jejunal (10.50 +/- 4.31 micrograms mL-1) and ileal
      (5.25 +/- 1.67 micrograms mL-1) contents at 4 h, and colonic contents (8.94 +/-
      0.65 micrograms mL-1) at 8 h.

PMID- 9533115
TI  - Techniques of paediatric modified ultrafiltration: 1996 survey results.
AB  - In September 1996, perfusionists from 50 paediatric open-heart surgery programmes
      were contacted to identify centres that are currently using the technique of
      modified ultrafiltration (MUF). Of the 50 centres contacted, 22 (44%) were
      utilizing the technique. These centres were surveyed on the following: neonatal
      circuit description, patient entry criteria, MUF circuit description, conduct of
      MUF, use of extracorporeal safety devices and/or modifications, and technical
      complications. All 22 centres used roller pumps and membrane oxygenators. In 19
      centres, MUF was utilized exclusively in the arteriovenous mode (86%), while two
      centres (9%) used the venovenous mode and one centre (5%) used both methods. Most
      (82%) of the 22 MUF centres used a blood cardioplegia system for myocardial
      preservation. After cardiopulmonary bypass (CPB), these blood cardioplegia
      systems were often converted for use as MUF circuits in a variety of ways. Other
      methods of accessing the CPB circuit for MUF included utilizing either a
      recirculation line or a dedicated port added to the circuit specifically for MUF.
      Blood flow rates during MUF, pump strategies, haemoconcentrator vacuum levels and
      endpoints were variable from centre to centre. Technical complications related to
      MUF were reported by 82% of the surveyed MUF centres. The most common
      complication, air cavitating into the circuit, was reported by 15 centres. From
      these data, we propose recommendations on the integration of MUF into CPB
      circuits, the conduct of perfusion during MUF, and appropriate safety
      considerations to minimize technical complications.

PMID- 9533114
TI  - Nonlinear pharmacokinetics of tissue-type plasminogen activator in three animal
      species: a comparison of mathematical models.
AB  - A recent study presented plasma concentrations of tissue-type plasminogen
      activator in three different animal species and at several different dose levels.
      A three-compartment mammillary model with capacity-limited elimination (of
      Michaelis-Menten form) was postulated to describe the data. In the present study,
      several alternative model structures are examined with the view of determining
      whether better fits can be obtained, whether linear models are significantly
      worse than nonlinear models, and whether all three compartments are really
      necessary.

PMID- 9533116
TI  - Modified ultrafiltration in paediatric cardiac surgery.
AB  - The effect of modified ultrafiltration (MUF) after cardiopulmonary bypass for
      paediatric cardiac surgery was evaluated in 138 children with moderate to severe
      congenital heart disease. The median age was 0.4 years (0 days to 6.5 years), and
      the weight 5.3 kg (2.2-20 kg). The operation was discontinued in six cases, three
      because of technical problems and three because of unstable circulation. One
      hundred-and-thirty-four patients were ultrafiltrated for a median of 12 min (2-27
      min) with an ultrafiltrate of median 44 ml/kg (6-118 ml/kg). Haematocrit was
      significantly increased from 28% (20-39%) to 36% (26-51%) and systolic arterial
      pressure from 56 mmHg (30-85 mmHg) to 74.0 mmHg (32-118 mmHg). Furthermore
      arterial oxygenation was significantly increased from 30.8 kPa (4.8-70.4 kPa) to
      34.1 kPa (4.9-80.6 kPa), and arterial carbon dioxide tension from 4.8 kPa (3.1
      7.3 kPa) to 5.1 kPa (3.1-7.6 kPa). Heart rate was significantly reduced from 145
      beats/min (92-201 beats/min) to 136 beats/min (88-200 beats/min). There were no
      significant differences in central venous pressure, left atrial pressure and base
      excess before and after MUF. MUF increases systolic blood pressure, haematocrit,
      arterial oxygen and carbon dioxide tension coming off bypass in paediatric
      cardiac surgery and reduces heart rate and postoperative fluid overload.

PMID- 9533117
TI  - Foetal bypass: concepts and controversies.
AB  - One of the most controversial and challenging surgical undertakings of the next
      century promises to be foetal cardiac surgery. Animal studies have been underway
      for several years to gain an understanding of the physiological mechanisms
      required to achieve this undertaking. Not since the days of crosscirculation has
      there been a maternal risk associated with open-heart surgery. The diagnosis of
      congenital heart defects with foetal ultrasound can now be made as early as 12
      weeks gestation. Simple cardiac abnormalities, such as valvular stenosis or
      atresia, alter intracardiac flow patterns and affect normal cardiac chamber
      development. Without early intervention, these complex lesions often require
      major surgical reconstruction, beginning in the neonatal period. Foetal cardiac
      bypass techniques have evolved from the use of roller pumps and bubble
      oxygenators primed with maternal blood to the use of an axial flow pump
      incorporated in a right atrial to pulmonary artery or aortic shunt. Because the
      blood entering the right atrium is oxygenated by the placenta, an oxygenator in
      the bypass circuit is probably not needed. The low prime axial flow pump system
      avoids the dilution of the foetus with the maternal adult haemoglobin and
      improves the outcome. A major focus of research has concentrated on maintenance
      of placental blood flow with the use of vasodilators and cyclooxygenase
      inhibitors. Investigation with primates will be necessary to confirm the
      placental physiology before human operations can be performed. As the foetal
      bypass challenges are overcome, there is the potential for a reduction in the
      number of complex cardiac lesions requiring early surgical intervention in the
      twenty-first century.

PMID- 9533118
TI  - Clinical oxygen transfer comparison of the Terumo Capiox SX18 and SX25 membrane
      oxygenators.
AB  - The purpose of this current study was to compare the Terumo Capiox SX18 (1.8 m2)
      with the recently released Capiox SX25 (2.5 m2). Specifically, their oxygen
      transfer slopes, degree of blood shunting, extrapolated maximum oxygen transfer,
      blood side pressure drop and oxygen transfer consistency were compared. The lower
      intercept value (0.209 vs 0.236) coupled with the flatter slope (0.00171 vs
      0.00225) of the oxygen transfer line for the SX25 is consistent with improved
      oxygen transfer performance. A lower FiO2 value would be predicted for the SX25,
      to achieve a specific PaO2 value, when the oxygen transfer requirement is equal
      for both devices. Extrapolated maximum oxygen transfer for the SX25 (462.6 ml
      O2/min) was 36.2% higher than that for the SX18 (339.6 ml O2/min). When indexed
      to membrane surface area, the SX18 (188.7 ml O2/m2/min performed 2.0% better than
      the SX25 (185.0 ml O2/m2/min). Both the slope (3.110 vs 3.744) and the intercept
      (4.595 vs 6.223) of the shunt fraction line were lower for the SX25, indicating
      that a lower shunt fraction would be predicted for all clinical blood flow rates.
      The slope (23.934 vs 22.443) and intercept values (-28.388 vs -22.650) of the
      pressure drop lines for the two devices indicate that the blood side pressure
      drop, over the range of clinical blood flows, were within 2% of each other.
      Oxygen transfer consistency, when expressed as the standard deviation of the
      oxygenator performance index and the percentage of predicted shunt, was not
      statistically different for the two devices.

PMID- 9533119
TI  - Effects of flow types in cardiopulmonary bypass on gastric intramucosal pH.
AB  - The aim of this study was to determine the relationship between splanchnic
      perfusion and oxygen consumption, and flow types in cardiopulmonary bypass (CPB),
      by measuring gastric intramucosal pH. Twenty patients undergoing elective open
      heart surgery were prospectively randomized to receive either pulsatile or
      nonpulsatile flow during CPB. Gastric intramucosal pH was measured using gastric
      tonometry. A flowmeter was used to measure the inferior caval vein flow. A
      catheter was inserted through the femoral vein to sample blood from the iliac
      vein. Systemic vascular resistance index, gastric intramucosal pH, inferior caval
      vein flow and arterial, inferior vena caval and iliac venous blood gases were
      recorded at different times. Gastric intramucosal pH decreased in all patients;
      only in the nonpulsatile group was this decrease statistically significant. After
      45 min of CPB, the pH was 7.37 +/- 0.03 compared with the prebypass value of 7.48
      +/- 0.04 (p = 0.00016). After weaning from CPB, the pH was 7.358 +/- 0.02
      compared with the prebypass value (p = 0.000037). At 2 h post-operatively the pH
      was 7.416 +/- 0.025 (p = 0.02). Systemic vascular resistance index rose in all
      patients during bypass in both groups. These changes did not have any statistical
      significances and after weaning from bypass returned to prebypass levels. We
      conclude that nonpulsatile flow in CPB is associated with reduced gastric
      intramucosal pH and the measurement of intramucosal pH during open-heart surgery
      provides important information about splanchnic perfusion.

PMID- 9533120
TI  - Total extrathoracic cardiopulmonary support with kinetic assisted venous
      drainage: experience in 50 patients.
AB  - Extrathoracic cardiopulmonary bypass is used in special situations when normal
      access to the right atrium and aorta is difficult or not practicable. Femero
      femoral bypass using gravity drainage is effective for partial cardiopulmonary
      support, but cannot usually provide adequate venous drainage for full circulatory
      support. Kinetic assisted venous drainage (KAVD) is the process of applying a
      controlled suction on the venous line with a kinetic pump to augment venous
      drainage. KAVD has been used in 50 patients where femero-femoral bypass was
      selected as the mode of circulatory support. These cases included: redo
      operations with significant sternal adhesions (15), minimally invasive port
      access cardiac surgery (12), haemodynamic instability (10), left thoracotomy
      (10), and others (3). In 11 cases, a second venous catheter was added because of
      protocol. No appreciable increase in venous return occurred with the addition of
      a second drainage catheter. All patients were adequately supported and a 20-40%
      increase in venous return was observed once KAVD was implemented. A wide variety
      of different venous catheters have been used with KAVD. Optimal use relates to
      having a thin-walled catheter with multiple side holes, not exerting an excessive
      negative pressure with the pump and positioning the catheter tip at the right
      atrio-superior vena cava junction. Optimal catheter tip placement is enhanced by
      using transoesophageal echocardiography. KAVD is best regulated by measuring the
      siphon generated by the kinetic pump. When the inlet pressure is properly
      monitored and controlled, KAVD can provide adequate venous drainage to completely
      support the circulation on a single femoral venous cannula.

PMID- 9533121
TI  - Myocardial preconditioning using adenosine: review and clinical experience.
AB  - Adenosine is an endogenous nucleotide and a breakdown product of adenosine
      triphosphate. Adenosine has been proposed as a mediator of the ischaemic
      preconditioning phenomenon. Ischaemic reperfusion injury incurred during and
      following cardiopulmonary bypass contributes to depressed myocardial function
      after cardiac surgery. It is believed that administering adenosine via the aortic
      root, immediately following aortic crossclamping as well as just prior to removal
      of the aortic crossclamp, provides myocardial preconditioning resulting in
      improved cardiac protection during ischaemic arrest and retarding ischaemic
      reperfusion injury. A retrospective analysis was done utilizing consecutive
      patients undergoing coronary artery bypass grafting performed by the same
      surgeon. Some of the patients received myocardial preconditioning with adenosine.
      A comparison was made in postoperative cardiac function between patients who
      underwent myocardial preconditioning and those who did not receive adenosine.
      Results demonstrate a greater improvement in postoperative cardiac function, when
      compared to preoperative values, in those patients receiving myocardial
      preconditioning with adenosine.

PMID- 9533122
TI  - Factors affecting levels of genetic diversity in natural populations.
AB  - Genetic variability is the clay of evolution, providing the base material on
      which adaptation and speciation depend. It is often assumed that most
      interspecific differences in variability are due primarily to population size
      effects, with bottlenecked populations carrying less variability than those of
      stable size. However, we show that population bottlenecks are unlikely to be the
      only factor, even in classic case studies such as the northern elephant seal and
      the cheetah, where genetic polymorphism is virtually absent. Instead, we suggest
      that the low levels of variability observed in endangered populations are more
      likely to result from a combination of publication biases, which tend to inflate
      the level of variability which is considered 'normal', and inbreeding effects,
      which may hasten loss of variability due to drift. To account for species with
      large population sizes but low variability we advance three hypotheses. First, it
      is known that certain metapopulation structures can result in effective
      population sizes far below the census size. Second, there is increasing evidence
      that heterozygous sites mutate more frequently than equivalent homozygous sites,
      plausibly because mismatch repair between homologous chromosomes during meiosis
      provides extra opportunities to mutate. Such a mechanism would undermine the
      simple relationship between heterozygosity and effective population size. Third,
      the fact that related species that differ greatly in variability implies that
      large amounts of variability can be gained or lost rapidly. We argue that such
      cases are best explained by rapid loss through a genome-wide selective sweep, and
      suggest a mechanism by which this could come about, based on forced changes to a
      control gene inducing coevolution in the genes it controls. Our model, based on
      meiotic drive in mammals, but easily extended to other systems, would tend to
      facilitate population isolation by generating molecular incompatabilities.
      Circumstances can even be envisioned in which the process could provide intrinsic
      impetus to speciation.

PMID- 9533123
TI  - Levels of genetic polymorphism: marker loci versus quantitative traits.
AB  - Species are the units used to measure ecological diversity and alleles are the
      units of genetic diversity. Genetic variation within and among species has been
      documented most extensively using allozyme electrophoresis. This reveals wide
      differences in genetic variability within, and genetic distances among, species,
      demonstrating that species are not equivalent units of diversity. The extent to
      which the pattern observed for allozymes can be used to infer patterns of genetic
      variation in quantitative traits depends on the forces generating and maintaining
      variability. Allozyme variation is probably not strictly neutral but,
      nevertheless, heterozygosity is expected to be influenced by population size and
      genetic distance will be affected by time since divergence. The same is true for
      quantitative traits influenced by many genes and under weak stabilizing
      selection. However, the limited data available suggest that allozyme variability
      is a poor predictor of genetic variation in quantitative traits within
      populations. It is a better predictor of general phenotypic divergence and of
      postzygotic isolation between populations or species, but is only weakly
      correlated with prezygotic isolation. Studies of grasshopper and planthopper
      mating signal variation and assortative mating illustrate how these characters
      evolve independently of general genetic and morphological variation. The role of
      such traits in prezygotic isolation, and hence speciation, means that they will
      contribute significantly to the diversity of levels of genetic variation within
      and among species.

PMID- 9533124
TI  - From genes to individuals: developmental genes and the generation of the
      phenotype.
AB  - The success of the genetic approach to developmental biology has provided us with
      a suite of genes that are involved in the regulation of ontogenetic pathways. It
      is therefore time to ask whether and how such genes might be involved in the
      generation of adaptive phenotypes. Unfortunately, the current results do not
      provide a clear answer. Most of the genes that have been studied by developmental
      biologists affect early embryonic traits with significant effects on the whole
      organism. These genes are often highly conserved which allows us to do
      comparative studies even across phyla. However, whether the same genes are also
      involved in short-term ecological adaptations remains unclear. The suggestion
      that early acting ontogenetic genes may also affect late phenotypes comes from
      the genetic analysis of quantitative traits like bristle numbers in Drosophila. A
      rough mapping of the major loci affecting these traits shows that these loci
      might correspond to well known early acting genes. On the other hand, there are
      also many minor effect loci that are as yet uncharacterized. We suggest that
      these minor loci might correspond to a different class of genes. In comparative
      studies of randomly drawn cDNAs from Drosophila we find that there is a large
      group of genes that evolve fast and that are significantly under-represented in
      normal genetic screens. We speculate that these genes might provide a large, as
      yet poorly understood, reservoir of genes that might be involved in the evolution
      of quantitative traits and short-term adaptations.

PMID- 9533125
TI  - Sexual conflict and speciation.
AB  - We review the significance of two forms of sexual conflict (different
      evolutionary interests of the two sexes) for genetic differentiation of
      populations and the evolution of reproductive isolation. Conflicting selection on
      the alleles at a single locus can occur in males and females if the sexes have
      different optima for a trait, and there are pleiotropic genetic correlations
      between the sexes for it. There will then be selection for sex limitation and
      hence sexual dimorphism. This sex limitation could break down in hybrids and
      reduce their fitness. Pleiotropic genetic correlations between the sexes could
      also affect the likelihood of mating in interpopulation encounters. Conflict can
      also occur between (sex-limited) loci that determine behaviour in males and those
      that determine behaviour in females. Reproductive isolation may occur by rapid
      coevolution of male trait and female mating preference. This would tend to
      generate assortative mating on secondary contact, hence promoting speciation.
      Sexual conflict resulting from sensory exploitation, polyspermy and the cost of
      mating could result in high levels of interpopulation mating. If females evolve
      resistance to make pre- and postmating manipulation, males from one population
      could be more successful with females from the other, because females would have
      evolved resistance to their own (but not to the allopatric) males. Between-locus
      sexual conflict could also occur as a result of conflict between males and
      females of different populations over the production of unfit hybrids. We develop
      models which show that females are in general selected to resist such matings and
      males to persist, and this could have a bearing on both the initial level of
      interpopulation matings and the likelihood that reinforcement will occur. In
      effect, selection on males usually acts to promote gene flow and to restrict
      premating isolation, whereas selection on females usually acts in the reverse
      direction. We review theoretical models relevant to resolution of this conflict.
      The winning role depends on a balance between the 'value of winning' and 'power'
      (relating to contest or armament costs): the winning role is likely to correlate
      with high value of winning and low costs. Sperm-ovum (or sperm-female tract)
      conflicts (and their plant parallels) are likely to obey the same principles.
      Males may typically have higher values of winning, but it is difficult to
      quantify 'power', and females may often be able to resist mating more cheaply
      than males can force it. We tentatively predict that sexual conflict will
      typically result in a higher rate of speciation in 'female-win' clades, that
      females will be responsible for premating isolation through reinforcement, and
      that 'female-win' populations will be less genetically diverse.

PMID- 9533127
TI  - Gulliver's further travels: the necessity and difficulty of a hierarchical theory
      of selection.
AB  - For principled and substantially philosophical reasons, based largely on his
      reform of natural history by inverting the Paleyan notion of overarching and
      purposeful beneficence in the construction of organisms, Darwin built his theory
      of selection at the single causal level of individual bodies engaged in
      unconscious (and metaphorical) struggle for their own reproductive success. But
      the central logic of the theory allows selection to work effectively on entities
      at several levels of a genealogical hierarchy, provided that they embody a set of
      requisite features for defining evolutionary individuality. Genes, cell lineages,
      demes, species, and clades-as well as Darwin's favoured organisms-embody these
      requisite features in enough cases to form important levels of selection in the
      history of life. R. A. Fisher explicitly recognized the unassailable logic of
      species selection, but denied that thsi real process could be important in
      evolution because, compared with the production of new organisms within a
      species, the origin of new species is so rare, and the number of species within
      most clades so low. I review this and other classical arguments against higher
      level selection, and conclude (in the first part of this paper) that they are
      invalid in practice for interdemic selection, and false in principle for species
      selection. Punctuated equilibrium defines the individuality of species and
      refutes Fisher's classical argument based on cycle time. In the second part of
      the paper, I argue that we have failed to appreciate the range and power of
      selection at levels above and below the organismic because we falsely extrapolate
      the defining properties of organisms to these other levels (which are
      characterized by quite different distinctive features), and then regard the other
      levels as impotent because their effective individuals differ so much from
      organisms. We would better appreciate the power and generality of hierarchical
      models of selection if we grasped two key principles: first, that levels can
      interact in all modes (positively, negatively, and orthogonally), and not only in
      the negative style (with a higher level suppressing an opposing force of
      selection from the lower level) that, for heuristic and operational reasons, has
      received almost exclusive attention in the existing literature; and second, that
      each hierarchical level differs from all others in substantial and interesting
      ways, both in the style and frequency of patterns in change and causal modes.

PMID- 9533126
TI  - The evolutionary genetics of speciation.
AB  - The last decade has brought renewed interest in the genetics of speciation,
      yielding a number of new models and empirical results. Defining speciation as
      'the origin of reproductive isolation between two taxa', we review recent
      theoretical studies and relevant data, emphasizing the regular patterns seen
      among genetic analyses. Finally, we point out some important and tractable
      questions about speciation that have been neglected.

PMID- 9533128
TI  - Measurement of dielectric properties of subcutaneous fat with open-ended coaxial
      sensors.
AB  - A three-layer model of stratum corneum, epidermis/dermis and subcutaneous fat has
      been developed for the capacitance of an open-ended coaxial line in contact with
      human skin. Applying the model, the electrical properties of subcutaneous fat can
      be calculated from skin dielectric measurements with three probes of different
      sizes. The three-layer model is based on a variational formula for the
      capacitance of the coaxial probe. An accurate approximation for the dielectric
      constant of the multilayer cutaneous structure is presented for the inverse
      problem of solving the dielectric constants of various layers. The method was
      tested at 300 MHz with breast cancer patients who often have radiotherapy-induced
      late alterations in the structure of subcutaneous fat due to the development of
      subcutaneous fibrosis. Measurements from 206 sites yielded a good agreement
      between the dielectric constant of subcutaneous fat and the clinical score for
      subcutaneous fibrosis.

PMID- 9533129
TI  - Gamma-spectroscopy investigation of radon daughter deposition on
      electrostatically charged surfaces.
AB  - The effect of static electricity on the deposition of radon daughters onto
      charged surfaces is determined by a combined experimental and theoretical
      analysis. Experiments with charged surfaces exposed to the air in a normal
      working environment are analysed to determine an empirical radon daughter
      deposition rate. This factor is utilized to estimate the daughter deposition on a
      human head which is exposed to similar conditions of air quality and static
      charging. The results indicate that typical levels of static electricity can
      enhance the deposition of radon daughters by orders of magnitude compared with
      the uncharged condition. The corresponding yearly alpha dose equivalents to the
      basal skin layer and to the eye exceed recommended limits. Beside having an
      important impact from the public health perspective, these results suggest that
      the obscure and contradictory correlations found between radon concentrations and
      adverse health effects may arise from a failure to account for the effects of
      static electricity.

PMID- 9533130
TI  - Calculation of radiation exposures from patients to whom radioactive materials
      have been administered.
AB  - Spreadsheet templates which calculate cumulative exposures to other persons from
      patients to whom radioactive materials have been administered have been developed
      by the authors. Calculations can be based on any specified single-, bi- or tri
      exponential whole-body clearance rate and a diurnal (or any other periodic)
      contact pattern. The time (post-administration) during which close contact should
      be avoided in order to constrain the radiation exposure and exposure rates to
      selected limits is also calculated using an iterative technique (Newton's
      method), and the residual activity at the time when contact can resume is also
      calculated. These templates find particular application in the calculation of
      exposures to persons who are in contact with patients who have received 131I for
      therapeutic purposes. The effect of changing dose limits, contact patterns and
      using individually derived clearance rates may be readily modelled.

PMID- 9533131
TI  - Complexity of Monte Carlo and deterministic dose-calculation methods.
AB  - Grid-based deterministic dose-calculation methods for radiotherapy planning
      require the use of six-dimensional phase space grids. Because of the large number
      of phase space dimensions, a growing number of medical physicists appear to
      believe that grid-based deterministic dose-calculation methods are not
      competitive with Monte Carlo methods. We argue that this conclusion may be
      premature. Our results do suggest, however, that finite difference or finite
      element schemes with orders of accuracy greater than one will probably be needed
      if such methods are to compete well with Monte Carlo methods for dose
      calculations.

PMID- 9533132
TI  - The effect of the nasopharyngeal air cavity on x-ray interface doses.
AB  - We investigated the impact of air cavities in head and neck cancer patients
      treated by photon beams based on clinical set-ups. The phantom for investigation
      was constructed with a cubic air cavity of 4 x 4 x 4 cm3 located at the centre of
      a 30 x 30 x 16 cm3 solid water slab. The cavity cube was used to resemble an
      extreme case for the nasal cavity. Apart from measuring the dose profiles and
      central axis percentage depth dose distribution, the dose values in 0.25 x 0.25 x
      0.25 cm3 voxels at regions around the air cavity were obtained by Monte Carlo
      simulations. A mean dose value was taken over the voxels of interest at each
      depth for evaluation. Single-field results were added to study parallel opposed
      field effects. For 10 x 10 cm2 parallel opposed fields at 4, 6 and 8 MV, the mean
      dose at regions near the lateral interfaces of the cavity cube were decreased by
      1 to 2% due to the lack of lateral scatter, while the mean dose near the proximal
      and distal interfaces was increased by 2 to 4% due to the greater transmission
      through air. Secondary build-up effects at points immediately beyond the air
      cavity cube are negligible using field sizes greater than 4 x 4 cm2. For most
      head and neck treatment, the field sizes are usually 6 x 6 cm2 or greater, and
      most cavity volumes are smaller than our chosen dimensions. Therefore, the
      influence of closed air cavities on photon interface doses is not significant in
      clinical treatment set-ups.

PMID- 9533133
TI  - On the use of unshielded cables in ionization chamber dosimetry for total-skin
      electron therapy.
AB  - The dosimetry of total-skin electron therapy (TSET) usually requires ionization
      chamber measurements in a large electron beam (up to 120 cm x 200 cm). Exposing
      the chamber's electric cable, its connector and part of the extension cable to
      the large electron beam will introduce unwanted electronic signals that may lead
      to inaccurate dosimetry results. While the best strategy to minimize the cable
      induced electronic signal is to shield the cables and its connector from the
      primary electrons, as has been recommended by the AAPM Task Group Report 23 on
      TSET, cables without additional shielding are often used in TSET dosimetry
      measurements for logistic reasons, for example when an automatic scanning
      dosimetry is used. This paper systematically investigates the consequences and
      the acceptability of using an unshielded cable in ionization chamber dosimetry in
      a large TSET electron beam. In this paper, we separate cable-induced signals into
      two types. The type-I signal includes all charges induced which do not change
      sign upon switching the chamber polarity, and type II includes all those that do.
      The type-I signal is easily cancelled by the polarity averaging method. The type
      II cable-induced signal is independent of the depth of the chamber in a phantom
      and its magnitude relative to the true signal determines the acceptability of a
      cable for use under unshielded conditions. Three different cables were evaluated
      in two different TSET beams in this investigation. For dosimetry near the depth
      of maximum buildup, the cable-induced dosimetry error was found to be less than
      0.2% when the two-polarity averaging technique was applied. At greater depths,
      the relative dosimetry error was found to increase at a rate approximately equal
      to the inverse of the electron depth dose. Since the application of the two
      polarity averaging technique requires a constant-irradiation condition, it was
      demonstrated than an additional error of up to 4% could be introduced if the
      unshielded cable's spatial configuration were altered during the two-polarity
      measurements. This suggests that automatic scanning systems with unshielded
      cables should not be used in TSET ionization chamber dosimetry. However, the data
      did show that an unshielded cable may be used in TSET ionization chamber
      dosimetry if the size of cable-induced error in a given TSET beam is pre
      evaluated and the measurement is carefully conducted. When such an evaluation has
      not been performed, additional shielding should be applied to the cable being
      used, making measurements at multiple points difficult.

PMID- 9533134
TI  - The effect of delta rays on the ionometric dosimetry of proton beams.
AB  - The interface effects arising in the measurement of absorbed dose by ionization
      chambers, owing to the inhomogeneity between the walls and the gas, have been
      evaluated by an analytical model. The geometrical situation considered here is
      appropriate for representing the behaviour of a plane-parallel ionization chamber
      exposed to a radiotherapeutic beam of protons. Two gases, dry air and tissue
      equivalent gas (methane based), as well as six materials commonly used in
      ionization chamber walls, i.e. graphite, A-150 tissue equivalent plastic, C-522
      air equivalent plastic, nylon type 6, polymethyl methacrylate and polystyrene,
      have been examined. The analysis of the results shows that, within the limits of
      the detector dimensions and proton energies commonly used in the dosimetry of
      radiotherapeutic beams, these effects, if not taken into account in the
      measurement interpretation, can entail deviations of up to about 2% with respect
      to the correct absorbed dose in gas.

PMID- 9533135
TI  - Numerical solutions of differential equations of an ionization chamber: plane
      parallel and spherical geometry.
AB  - A system of reduced differential equations generally valid for plane-parallel,
      cylindrical and spherical ionization chambers, which is appropriate for numerical
      solution, has been derived. The system has been solved numerically for plane
      parallel and spherical ionization chambers filled with air. The comparison of the
      calculated results of Armstrong and Tate, for plane-parallel ionization chambers,
      and Sprinkle and Tate, for spherical ionization chambers, with the present
      calculations has shown a good agreement. The calculated values for ionization
      chambers filled with CO2 were also in good agreement with the experimental data
      of Moriuchi et al.

PMID- 9533137
TI  - An alternative beam quality index for medium-energy x-ray dosimetry.
AB  - To determine absorbed dose to water it is essential that the radiation quality of
      the x-ray beam is known accurately. The unique method of defining the beam
      quality is to acquire a detailed knowledge of the photon spectrum at the point of
      measurement in water, but this is impractical. The aim of this work was to
      investigate a quality index that uniquely defines the ratio of mass-energy
      absorption coefficients of water to air at 2 cm deep in water ([(mu en/rho)w/a]z
      = 2,phi). Three parameters, HVL, mean energy at 2 cm deep in water and the ratio
      of the doses at 2 and 5 cm deep in water (D2/D5) were investigated as functions
      of [(mu en/rho)w/a]z = 2,phi. The quality index that best defines [(mu
      en/rho)w/a]z = 2,phi is the ratio of doses at 2 and 5 cm depth in water.

PMID- 9533136
TI  - A three-Gaussian fit of phantom scatter correction data.
AB  - The phantom scatter correction factor Sp of megavoltage photon beams can be
      accurately described using a three-Gaussian fit. The model leads to six
      parameters, with which Sp(r) is described as a smooth function of the field
      radius r for beam qualities in the range from 60Co up to 25 MV. The parameters
      allow Sp values to be calculated at intermediate beam energies and for any field
      shape. Calculated Sp(X, Y) values for rectangular fields (X, Y) can be
      subsequently used as reference values to compare with measured Sp(X, Y) values,
      for example when appraising a new beam.

PMID- 9533138
TI  - Ionization chambers for measuring air kerma integrated over beam area. Deviations
      in calibration values using simplified calibration methods.
AB  - Calibrations of kerma-area product meters (KAP meters) are often performed using
      simplified methods. The accuracy thus obtained can be insufficient, especially
      when the KAP meters are used for optimizing radiological procedures. The
      deviations between the best available calibration factor (k) and the simplified
      calibration factor (ks) were measured at different clinical x-ray installations.
      Depending on the type of x-ray installation and calibration method, the quotient
      ks/k ranged from 0.83 to 1.19, reflecting the error made in practice using these
      methods. A simple alternative calibration method based on comparison with a KAP
      meter calibrated by the best available method is described. Depending on tube
      potential and the stability of the electrometers, the uncertainty in the
      calibration factor derived with this method was between 3.8% and 5.6% (at 95%
      confidence level).

PMID- 9533139
TI  - Examination of aperture signals in digital radiography.
AB  - Lead discs have been widely used to measure scattered radiation in radiographic
      imaging. An alternative approach, which offers advantages in terms of practical
      simplicity and radiation dose efficiency, is based on measurements obtained using
      a narrow aperture. The use of such an aperture for scatter measurement is
      examined from an experimental perspective in this paper. The examination is based
      on analysing features in images of apertures of 0.5 mm to 10 mm in diameter using
      a digital fluoroscopy system. Clinical imaging conditions were simulated using a
      15 cm thickness of scattering material and a kilovoltage of 80 kVp. It was found
      that images of broad apertures consist of a transmitted signal, with primary and
      scatter components, which is surrounded by a skirt resulting from scatter.
      Furthermore, it was found that the skirt and the scatter component of the
      transmitted signal become negligible for narrow apertures. It was also found that
      a 1.5 mm aperture generates a scatter-free primary signal within the limits of
      accuracy of the detection system employed. This outcome was confirmed on the
      basis of accurate densitometric measurements and aperture signals which were
      independent of air gap. It is concluded that the signal measured using a 1.5 mm
      aperture can be related to the open field signal to determine the scatter signal
      and that this is an accurate method for such measurement with this experimental
      arrangement.

PMID- 9533140
TI  - Limitations of clinical CT in assessing cortical thickness and density.
AB  - The peak CT number (CT) and full width at half maximum (FWHM) were obtained from
      the image profiles of aluminium of thickness ranging from 0.1-9.5 mm. The scans
      were performed at different fields of view (FOVs) and with different
      reconstruction algorithms ('bone' and 'standard'). Above 3 mm, CT and FWHM
      provide measures of the density and thickness which are largely independent of
      FOV (i.e. pixel size) and algorithm. Below 3 mm, CT falls progressively whilst
      FWHM remains relatively constant. At these small thicknesses the effect of FOV on
      CT is more pronounced when the bone algorithm is used, whilst FWHM remains
      relatively constant and independent of both FOV and algorithm. The results are
      discussed in terms of thickness relative to pixel size and spatial resolution as
      characterized by the point spread function. A linear relationship was found
      between the product CT x FWHM and thickness that is independent of both FOV and
      algorithm. This product may be useful in studies of cortical bone and changes due
      to osteoporosis.

PMID- 9533141
TI  - A potential diagnostic application of magnetization transfer contrast: an in
      vitro NMR study of excised human thyroid tissues.
AB  - A series of freshly excised thyroid tissues was analysed using a nuclear magnetic
      resonance spectrometer and then subjected to routine histo-pathology examination.
      Whilst simple T1 values for normal tissue and goitre are not significantly
      different, the degree of intra-subject T1 and T1s variability is shown to be an
      indicator of benign thyroid disease. Using data collected from an inversion
      recovery sequence performed with and without magnetization transfer, a
      magnetization transfer rate constant was calculated for each tissue sample. These
      data suggest that this parameter may provide in vivo discrimination between
      follicular cancer and follicular adenoma.

PMID- 9533142
TI  - Optimal design of planar-concave collimators for SPECT--an analytical approach.
AB  - In this paper we present an analytical tool for the design and optimization of
      planar-concave collimators for SPECT. We conclude that a single general planar
      concave collimator that eliminates the non-isotropic blurring for all SPECT
      applications does not exist. On the other hand, it is possible to achieve pseudo
      optimal collimators for different clinical applications by a careful choice of
      the design parameters. By classifying the clinical applications into two groups,
      for instance body and brain studies, the non-isotropic blurring for most SPECT
      situations may be dramatically reduced by means of planar-concave collimators.
      The results based on Monte Carlo simulations show that the shape of the point
      source response function of the reconstructed image obtained from the planar
      concave collimator is more isotropic than that obtained from a conventional
      parallel-hole collimator. Specifically, the ratio of the FWHM of the
      reconstructed point response function in the radial and tangential direction is
      increased from 0.5 for the parallel-hole to 0.85 for the planar-concave
      collimator for sources 200 mm away from the centre of rotation.

PMID- 9533143
TI  - Parametric image reconstruction using spectral analysis of PET projection data.
AB  - Spectral analysis is a general modelling approach that enables calculation of
      parametric images from reconstructed tracer kinetic data independent of an
      assumed compartmental structure. We investigated the validity of applying
      spectral analysis directly to projection data motivated by the advantages that:
      (i) the number of reconstructions is reduced by an order of magnitude and (ii)
      iterative reconstruction becomes practical which may improve signal-to-noise
      ratio (SNR). A dynamic software phantom with typical 2-[11C]thymidine kinetics
      was used to compare projection-based and image-based methods and to assess bias
      variance trade-offs using iterative expectation maximization (EM) reconstruction.
      We found that the two approaches are not exactly equivalent due to properties of
      the non-negative least-squares algorithm. However, the differences are small (<
      5%) and mainly affect parameters related to early and late time points on the
      impulse response function (K1 and, to a lesser extent, VD). The optimal number of
      EM iteration was 15-30 with up to a two-fold improvement in SNR over filtered
      back projection. We conclude that projection-based spectral analysis with EM
      reconstruction yields accurate parametric images with high SNR and has potential
      application to a wide range of positron emission tomography ligands.

PMID- 9533144
TI  - The P-transform and photoacoustic image reconstruction.
AB  - Photoacoustic imaging is a new imaging modality which converts pressure signals
      received by an array of transducers to a regional distribution of electromagnetic
      absorption density. This paper presents a rigorous theory for photoacoustic image
      reconstruction in a concise format. A new type of transform, the P-transform, is
      proposed, analysed and presented as the main mathematical tool for
      reconstruction. It is proved that photoacoustic image reconstruction is
      intrinsically a three-dimensional (3D) procedure. The spatial smear function
      (SSF) is introduced. To complete photoacoustic image reconstruction an integral
      equation must be solved, which is replaced by a matrix approach in a discretized
      space. An example using synthetic data proves the validity of the photoacoustic
      image reconstruction theory proposed in the paper. The example shows that even
      the first-order approximation of photoacoustic image reconstruction gives good
      agreement with reality. It is also seen from the example that the accuracy and
      noise immunity of the reconstruction procedure depend on the experimental
      arrangement.

PMID- 9533146
TI  - Experimental procedure for the manufacture and calibration of polyacrylamide gel
      (PAG) for magnetic resonance imaging (MRI) radiation dosimetry.
AB  - A simple methodology for the manufacture and calibration of polyacrylamide gel
      (PAG) for magnetic resonance imaging (MRI) radiation dosimetry is presented to
      enable individuals to undertake such work in a routine clinical environment.
      Samples of PAG were irradiated using a linear accelerator and imaged using a 0.5
      T (22 MHz) Philips Gyroscan MRI scanner. The mean spin-lattice relaxation rate
      was measured using a 'turbo-mixed' sequence, consisting of a series of 90 degrees
      pulses, each followed by acquisition of a train of spin echoes. The mean
      sensitivity for five different batches of PAG in the range up to 10 Gy was
      calculated to be 0.0285 s-1 Gy-1 for the mean spin-lattice relaxation rate with a
      percentage standard deviation of 1.25%. The overall reproducibility between
      batches was calculated to be 2.69%. This methodology, which introduces the novel
      use of pre-filled nitrogen vials for calibration, has been used to develop
      techniques for filling anatomically shaped anthropomorphic phantoms.

PMID- 9533145
TI  - Improved continuous light diffusion imaging in single- and multi-target tissue
      like phantoms.
AB  - The image reconstruction enhancement schemes of total variation minimization,
      dual meshing and iterative spatial filtering have been applied to laboratory data
      collected from continuous light illumination of tissue-like phantoms. Experiments
      include both single- and multi-target cases where variations in object size (4 mm
      to 20 mm), position (centred to near boundary) and contrast with the background
      (2:1 to 8:1) have been explored. The results show that dramatic improvements in
      image quality have been obtained in terms of geometric and spatial resolution
      measures relative to those previously reported for continuous light, but
      quantitative information on the actual optical properties of embedded
      heterogeneities is still lacking. Specifically, the geometric characteristics of
      object size, position and shape are generally accurate to 10-20% and the spatial
      resolution metrics of background-to-object size and neighbouring-edge separation
      are approximately 10:1. Direct comparisons are also made with images obtained
      with intensity-modulated light under identical experimental conditions. Images
      from intensity-modulated light are found to be superior to continuous light in
      several important ways, most notably in terms of the ability to quantitatively
      discriminate the optical property values of embedded targets from the surrounding
      background. Continuous-light images are also found to have centrally located
      artefacts in many instances which do not appear in the corresponding intensity
      modulated cases.

PMID- 9533147
TI  - Execution times of five reconstruction algorithms in 3D positron emission
      tomography.
AB  - Various analytical, iterative and rebinning algorithms have been proposed for 3D
      reconstruction in positron emission tomography. This paper examines execution
      times of five analytical and rebinning algorithms. Meaningful comparisons are
      obtained by using similar software modules in all implementations. Reconstruction
      times are shown to differ by vast amounts: the Favor algorithm of Defrise et al
      is more than twice as fast as the widely used reprojection algorithm of Kinahan
      and Rogers; the Fourier rebinning algorithm (Fore) recently developed by Defrise
      is more than 15 times faster than the reprojection algorithm.

PMID- 9533148
TI  - [The treatment of erectile dysfunction: what are the objectives and the
      methods?].
AB  - Despite considerable progress, the treatment of erectile insufficiency is often
      difficult due to its usually multifactorial aetiology and to the fact that the 3
      components of a satisfying sex life are: 1) Sufficient penile rigidity with no
      other associated sexual dysfunction, 2) an adapted mental state, 3) a loving
      relationship with the partner. All of these parameters must be taken into account
      to ensure a lasting success, hence the need for a global approach rather than an
      approach localized to the organ. Consequently, there is not one, but several
      treatments which must be adapted to each case. The rarity of easily curable
      aetiologies explains the very widespread use of symptomatic treatments and the
      primordial place of clinical assessment. A consensus has currently been reached
      concerning: a) give the patient objective information, an essential prerequisite
      for the choice and success of treatment, b) start by proposing minimally invasive
      medical treatments, c) emphasize the value of a multidisciplinary approach in the
      case of failure, d) recognize the fact that achievement of a rigid penis is not
      necessarily synonymous with cure. In practice, two situations can be
      distinguished: 1) in the presence of predominantly psychogenic disorders, sex
      therapy and/or sexual advice can be used in all patients, either alone or in
      combination with drug treatments and/or a vacuum device (especially in the case
      of failure of either of these treatments), 2) in the presence of predominantly
      organic abnormalities which are not easily curable drug treatments and/or vacuum
      must be proposed first, but sexological management is always useful in these so
      called "organic" patients. Prosthetic surgery, the only approach with
      demonstrated efficacy, is only indicated following failure of medical treatment,
      after rigorous selection. The release onto the market, in the near future, of
      promising new oral or intraurethral drugs used "on request" will certainly modify
      the treatment hierarchy. Due to their acceptability and efficacy, they will
      certainly be prescribed as first-line treatment, regardless of the origin of the
      erectile insufficiency. However, the therapeutic approach in the case of failure
      will remain unchanged. Erectile insufficiency can effectively be treated provided
      a rigorous assessment is performed.

PMID- 9533149
TI  - [Urologic management of cystine lithiasis in the upper urinary tract. Modalities
      and indications].
AB  - Cystine urinary stones is a relatively rare hereditary disorder of dibasic amino
      acid transport characterized by frequent recurrences. The management of these
      stones remains problematical despite the remarkable progress in the urological
      treatment of upper urinary tract stones. Cystine stones are particularly
      refractory to extracorporeal shock waves and relatively inaccessible to dye
      pulsed laser (504 nm). Apart from this exception, endourological techniques often
      represent the most appropriate therapeutic solution, but they are associated with
      significant morbidity. The physicochemical characteristics of these stones also
      allow dissolution by urinary alkalinization or the formation of disulfide
      compounds. In parallel with oral treatments, which constitute the basis of
      prevention of recurrence, dissolution can be obtained by direct perfusion of the
      urinary tract. This approach often requires irrigation for several weeks with a
      risk of the specific complications of catheterization, especially percutaneous
      catheterization. Prophylaxis, essentially consisting of dilution and dissolution
      of urinary cystine, raises the problem of the potential adverse effects of drug
      treatment. Cystinuria is easily detectable and can be investigated either
      systematically or only in the families concerned. However, the incidence as well
      as the frequently benign nature of cystinuria tend to limit its value and its
      indications.

PMID- 9533150
TI  - [Bladder tumors in young patients].
AB  - Bladder tumours classically affect the elderly, but can also occur in young
      adults. The authors studied the prognosis of these tumours in patients under the
      age of 40. In their experience, these tumours represent 3.27% of all bladder
      tumours. 26 patients with a mean age of 34 years (20-40 years), 8 under the age
      of 30, were studied. There was a marked male predominance (23 males, 3 females).
      The tumour was a transitional cell carcinoma in 25 cases and a squamous cell
      carcinoma in 1 case. It was superficial in 11 cases and invasive in 15 cases.
      Transurethral resection and cystectomy were performed in 9 cases of superficial
      tumours and 11 cases of invasive tumours, respectively. In the group of
      superficial tumours, a favourable course was observed in 7 cases, with 3 cases of
      recurrence and 1 case of progression. In the group of invasive tumours, a
      favourable course was observed in 6 cases, recurrence was observed in 2 cases and
      5 patients died. Superficial tumours therefore have a better prognosis in
      subjects under the age of 30. Invasive tumours are more frequent and often
      advanced, suggesting a marked potential for progression. Their prognosis depends
      on tumour stage, and is not correlated with age.

PMID- 9533151
TI  - [Can the prostatic capsule be preserved during cystectomy for bladder tumors: a
      study of urethral and prostatic involvement in the cystectomy specimens].
AB  - OBJECTIVES: To evaluate the frequency of urethral and prostatic lesions on
      cystectomy specimens for bladder tumour. MATERIAL AND METHODS: This retrospective
      histological study was based on 260 specimens: radical cystectomies performed in
      7 operative sites. The prostate and urethra were analysed in 3 planes (upper,
      middle and lower thirds). The apex was studied separately. Urethral invasion was
      identified by continuity of the tumour or by the presence of vesical CIS.
      RESULTS: Urethral involvement is frequent (30.6% cases) essentially due to
      contiguous invasion (43/80). CIS is the second pathological association (44
      urethral CIS/75 bladder CIS). Prostatic adenocarcinoma was present in 17.8% of
      cases with a Gleason score > 6 for 30% of lesions. CONCLUSION: The high frequency
      of urethral and prostatic involvement does not justify preservation of the
      prostate during cystectomy. A serial prospective study should define the precise
      criteria able to minimize the risk of conservative surgery.

PMID- 9533152
TI  - [W enterocystoplasty with resorbable staples: technic and functional results.
      Preliminary study].
AB  - INTRODUCTION: The use of absorbable staples for enterocystoplasty allows a marked
      reduction of the operating time. The long-term results on continence need to be
      evaluated at result term before adopting this technique. METHODS: Eight patients
      underwent "W" enterocystoplasty performed with absorbable staples according to
      the so-called "Detroit" technique, with direct uretero-ileal anastomosis. The
      continence of these patients was evaluated by clinical follow-up and urodynamic
      assessment (3 patients). Quality of life was studied by a questionnaire sent to
      the patient. RESULTS: The mean operating time was 5 hours 20 minutes, the plasty
      was performed in 25 to 35 minutes. The mean follow-up was 18.7 months, during
      which two uretero-ileal strictures were diagnosed. 7 of the 8 patients have a
      good diurnal continence (no leaks) and 1 patient has moderate continence (1
      protection). Nocturnal continence was considered to be good in 3 cases, moderate
      in 2 cases and poor in 3 cases (> 1 protection). Four of the patients evaluated
      by questionnaire reported urinary disorders. CONCLUSION: The use of absorbable
      staples allows a definite reduction of the operating time, for a modes excess
      cost and satisfactory functional results.

PMID- 9533153
TI  - [Continent urinary diversion using a tubulized sigmoid segment. An alternative to
      trans-appendicular diversion].
AB  - OBJECTIVE: The authors propose the use of a sigmoid tube reimplanted submucosally
      in the bladder and brought out onto the skin in the midline or in the umbilicus
      as a method of continent urinary diversion allowing urinary catheterization
      several times a day when the appendix cannot be used. MATERIALS AND METHODS:
      Three adolescents with neurogenic bladder were treated according to this
      procedure; the summit of the sigmoid colon loop was selected to form a continent
      tube from a segment 4 cm wide, opened along its antimesenteric border and sutured
      longitudinally. RESULTS: The postoperative course was uneventful in all 3 cases.
      The cystostomy was continent. Catheterizations were easily performed. CONCLUSION:
      Creation of a sigmoid tube is an alternative to the use of the appendix for
      continent urinary diversion according to Mitrofanoff's procedure. This technique
      can always be performed due to the proximity of the sigmoid colon and bladder,
      which is not always the case with the appendix. This tube is richly vascularized
      and presents the advantage of a very narrow mesocolon which does not interfere
      with creation of the intravesical submucosal tunnel.

PMID- 9533154
TI  - [The absence of metabolic disorders 8 years after detubulized Z entero
      cystoplasty].
AB  - Intestinal resection can lead to decreased gastrointestinal absorption of various
      metabolic substances. The use of these intestinal segments as materials for
      urinary tract reconstruction can also induce metabolic disorders. The authors
      studied the long-term metabolic consequences of replacement enterocystoplasty
      after radical cystectomy for bladder cancer.

PMID- 9533156
TI  - [The value of examination and treatment using laparoscopy in non-palpable testes:
      apropos of a series of 48 cases].
AB  - OBJECTIVES: Laparoscopy now constitutes the reference technique for the diagnosis
      and treatment of cryptorchid testes. We report our experience over the last three
      years (1993-1996). MATERIAL AND METHODS: 48 strictly impalable testes were
      investigated in 46 boys between the ages of 11 months and 14.5 years (mean age:
      40 months). The intraperitoneal investigation assessed both deep inguinal regions
      looking for gonads, vas deferens and pedicles. Intra-abdominal gonads were
      ligated and their pedicle was sectioned laparoscopically allowing transinguinal
      descent 6 months later according to the Fowler-Stephens technique. RESULTS: We
      found 21 cases of typical antenatal torsion, including one bilateral case
      (pedicle and vas deferens present, but gonad absent), one case of total
      unilateral agenesis and 3 cases of incomplete agenesis (only the vas deferens was
      detected) and performed three resections of the gonadal rest for histological
      examination. The first-stage of cryptorchid testis descent was performed in 20
      cases, by laparoscopy in 19 cases (1 failure of insufflation). Definitive descent
      was possible in 13 cases, with early onset of atrophy in only one case.
      CONCLUSION: Laparoscopy is therefore a simple technique, allowing a definitive
      diagnosis and two-stage descent without increasing the risk of testicular
      atrophy.

PMID- 9533155
TI  - [Preliminary results of the treatment of 44 patients with localized cancer of the
      prostate using transrectal focused ultrasound].
AB  - OBJECTIVE: To evaluate the efficacy and morbidity of treatment of localized
      prostatic cancer using transrectal high-intensity focused ultrasound. MATERIAL
      AND METHODS: 44 patients (mean age: 72 years) with clinical stage T1 (20) or T2
      (24) prostatic cancer, not eligible for radical prostatectomy, were treated by
      two different prototypes of the Ablatherm (Technomed Medical System). The second
      prototype includes several safety devices designed to reduce morbidity. 99
      sessions were performed, i.e. an average of 2.25 sessions per patient: the
      prostate was treated in one session (5 patients), 2 sessions (26 patients), 3
      sessions (10 patients), or 4 sessions (3 patients), usually under spinal
      anaesthesia. The mean PSA was 9.92 ng/ml and the mean prostatic weight was 37 g.
      RESULTS: Complications occurred in 10 (50%) of the first 20 patients treated
      (1993-1995): 2 recto-urethral fistulas, 2 asymptomatic rectal burns, 2 cases of
      stable urinary retention, 1 case of severe incontinence, 3 cases of bladder neck
      sclerosis, and 1 febrile urinary tract infection. In the 24 patients treated
      subsequently (1995-1997), complications occurred in only 4 patients (16%): 1 case
      of stable urinary retention, 1 febrile urinary tract infection, 1 case of bladder
      neck sclerosis, 1 case of stress incontinence. A complete response (repeated
      negative follow-up biopsies) was obtained in 27 patients (61%). The mean post
      treatment PSA level in patients of this group was 1.09 +/- 1.06 and remained
      stable (mean follow-up: 346 days; range: 60-1250). A residual cancer was detected
      in 17 patients (39%). 8 patients were considered to be failures (mean post
      treatment PSA: 4.8 ng/ml) and received adjuvant treatment (hormonal: 3; external
      radiotherapy: 5). Complementary treatment by focused ultrasound will be performed
      in another 9 patients, if their PSA rises above 3 ng/ml (patients of this group
      are symptomatic with a mean post-treatment PSA of 1.6 ng/ml). CONCLUSION: The
      morbidity of treatment by transrectal focused ultrasound has now been reduced.
      These results suggest that this new treatment can constitute a useful option for
      certain patients with localized cancer, not suitable for radical prostatectomy.

PMID- 9533158
TI  - [Contralateral aneurysm-like adrenal gland metastasis of a renal adenocarcinoma].
AB  - The authors report a case of adrenal metastasis contralateral to a renal cell
      carcinoma in a 74-year-old patient who had undergone right radical nephrectomy
      for renal cell carcinoma. Nine months later, computed tomography revealed a
      hypervascular mass considered to be an aneurysm of the splenic artery.
      Arteriography led to the diagnosis of hypervascular adrenal tumour. Left
      adrenalectomy was performed. Histological examination showed a metastasis from
      renal cell carcinoma. This is an unusual form of renal cancer metastasis. Its
      treatment and prognosis are discussed.

PMID- 9533157
TI  - [Distal vascular access for chronic hemodialysis in patients over 65 years of
      age. Surgical results].
AB  - OBJECTIVE: To evaluate the results of vascular accesses for chronic haemodialysis
      in elderly patients. MATERIAL AND METHODS: 56 consecutive vascular accesses for
      haemodialysis were performed from November 1993 to December 1995 in patients over
      the age of 65 years. The policy adopted was to prefer distal accesses: only
      forearm accesses, primary arteriovenous fistula (AVF) or radio-M venous
      bioprosthesis shunt (AVS) were performed. Surgical or interventional radiological
      reoperation rates and abandonment rates were evaluated. RESULTS: 13 AVF (mean
      age: 74.5 years) and 43 AVS (mean age: 73.8 years) were analysed. The mean number
      of reoperations was significantly higher in the shunt group. 1 out of 13 AVF was
      abandoned versus 9 out of 43 AVS (no significant difference). DISCUSSION: AVS
      gave poor results in terms of reoperation rate, inducing a high cost and
      impairment of the quality of life of these patients. Their survival in this
      population was comparable to that of AVF. Several teams prefer to perform first
      line humero-cephalic or humero-basilic arteriovenous fistulas whenever a simple
      fistula in the forearm cannot be performed. They appear to give better results,
      but their use in the elderly is poorly evaluated. Peritoneal dialysis may be
      preferable to haemodialysis in the elderly. As vascular accesses are increasingly
      performed in elderly subjects with a reduced life expectancy, protection of the
      proximal venous capital does not appear to be a sufficient argument to justify
      the use of AVS in this population. CONCLUSION: This study encouraged us to
      abandon the use of prostheses in the forearm in favour of direct accesses in the
      arms.

PMID- 9533159
TI  - [Solitary fibrous tumor of the seminal vesicles: apropos of a case].
AB  - Solitary fibrous tumours constitute a rare disease, which has never previously
      been described in the seminal vesicles. We report a case of solitary fibrous
      tumour of the right seminal vesicle in a 53-year-old man. The diagnosis of
      seminal vesicle tumour was based on transrectal ultrasonography and MRI. The
      histological diagnosis was established after surgical resection of this tumour.
      The small biopsy samples and the heterogeneous appearance of these lesions make
      it difficult to establish the diagnosis on biopsies alone. The surgical attitude
      to solitary fibrous tumour of the seminal vesicle depends on the clinical
      features and the course of the lesion.

PMID- 9533160
TI  - [Bolande tumor in adults: apropos of a case].
AB  - Bolande's tumour or congenital mesoblastic nephroma is essentially a tumour of
      infants under the age of one year and is rare in adults, in whom only 10 cases
      have been described. The authors report the 11th case in a 30-year-old woman, in
      whom a right renal tumour was discovered during ultrasonography at 34 weeks of
      pregnancy. Radical nephrectomy was performed after delivery, with a favourable
      course at 3 years, with no recurrence or metastasis. The aetiopathogenic and
      diagnostic aspects are discussed, with emphasis on the possibility of a hormonal
      inducing factor in the histogenesis of this tumour.

PMID- 9533161
TI  - [Bladder hemangioma: a rare cause of hematuria. Apropos of a case. Review of the
      literature].
AB  - The authors report a clinical case of multiple vesical haemangioma, a rare
      congenital benign vascular tumour essentially affecting children and young
      adults. These tumours may be solitary or multiple, and essentially spread to the
      bladder wall. They are sometimes associated with other sites, such as in the rare
      Klippel-Trenaunay-Weber syndrome. Usually presenting in the form of macroscopic
      haematuria, they are essentially diagnosed by endoscopy. Depending on the case,
      treatment consists of partial cystectomy or laser photocoagulation, rather than
      endoscopic resection, which is haemorrhagic and incomplete, or radiotherapy,
      which is insufficient. Selective arterial embolization is rarely used.

PMID- 9533162
TI  - [The efficacy of trans-urethral prostatic microwave thermotherapy].

PMID- 9533163
TI  - [Endoscopes in urology: disinfection, sterilization, labeling and tracking.
      Circulars and decrees. Modes of application and commentary. The Committee of
      Infectious Diseases of the French Association of Urology. Congressional forum UFA
      -Paris, November 1996. DGS Circular 20 October 1997].
AB  - Administrative texts published in 1995, 1996 and 1997, have reinforced
      materiovigilance and impose disinfection precautions for endoscopes. The steps of
      disinfection of non-sterilizable endoscopes are: preliminary treatment, rinsing,
      actual disinfection, final rinsing, storage (see: Progres en Urologie, 1997, 7,
      505-507). Each procedure from collection of the endoscope until storage must be
      defined by written standard operating procedures validated by CLIN. The risk of
      transmission of Creutzfeld-Jakob disease requires autoclaving, which is only
      possible, at the present time, with the most recent rigid endoscopes. Until
      disinfection has become generalized, the traceability of endoscopes (labelling,
      utilization files) must be established on the model recommended for
      haemovigilance (circular of 02/04/96).

PMID- 9533164
TI  - [Raphael-Bienvenu Sabatier (1732-1811). Celebrated surgeon and forerunner of
      urology].
AB  - The authors sketch the portrait of Sabatier, a famous surgeon and academic, who
      made a major contribution to the development of urology and to its recognition as
      an autonomous medical discipline, by means of his lectures and publications. In
      particular, they describe Sabatier's concepts concerning urinary retention.

PMID- 9533165
TI  - Psychoneuroimmunology and the cytokine action in the CNS: implications for
      psychiatric disorders.
AB  - 1. Parallel to the current rapid development of new immunological methods, immune
      mechanisms are gaining more importance for our understanding of psychiatric
      disorders. The purpose of this article is to review basic and clinical
      investigations that elucidate the relationship between the CNS and the immune
      system. 2. The topical literature dealing with the interactions of immune system,
      neurotransmitters, psychological processes, and psychiatric disorders, especially
      in relation to cytokines, is reviewed. 3. An activation of the immune system in
      schizophrenia and depressive disorders has repeatedly been described. Cytokines,
      actively transported into the CNS, play a key role in this immune activation. It
      was recently observed that cytokines activate astrocytes and microglia cells,
      which in turn produce cytokines by a feedback mechanism. Moreover, they strongly
      influence the dopaminergic, noradrenergic, and serotonergic neurotransmission. 4.
      There are indications that the cascade of cytokines can be activated by neuronal
      processes. These findings close a theoretical gap between stress and its
      influence on immunity. Psychomotor, sickness behavior and sleep are related to IL
      1; disturbances of memory and cognitive impairment are to IL-2, in part also to
      TNF-alpha. The hypersecretion of IL-2 is assumed to have a prominent influence on
      schizophrenia, and IL-6, on depressive disorders. 5. Although single cytokines
      most likely do not have a specificity for certain psychiatric disorders, a
      characteristic pattern of cytokine actions in the CNS, including influences of
      the cytokines on the blood-brain barrier, seems to play a role in psychiatric
      disorders. This may have therapeutic implications for the future.

PMID- 9533166
TI  - The pharmacology of native N-methyl-D-aspartate receptor subtypes: different
      receptors control the release of different striatal and spinal transmitters.
AB  - 1. N-methyl-D-aspartate (NMDA) increases the release of radiolabelled dopamine,
      GABA, acetylcholine and spermidine from rat striatal slices and of noradrenaline
      from the dorsal cervical spinal cord. 2. These five responses show differing
      sensitivities to NMDA and also to a variety of competitive antagonists, NMDA
      channel blockers, glycine antagonists and polyamine site antagonists. 3.
      Inhibitory activity profiles for 20 different antagonists are presented. All
      compounds tested showed some degree of selectivity with regard to the different
      responses and each response showed particular characteristics that suggested
      mediation by a particular native NMDA receptor subtype. 4. Receptors controlling
      dopamine, GABA and noradrenaline release were generally more sensitive to most
      antagonists compared to those controlling acetylcholine and spermidine release.
      5. Receptors controlling spermidine release were furthermore insensitive to
      magnesium, argiotoxin, ifenprodil and eliprodil and displayed low sensitivity to
      memantine, dextrorphan and dextromethorphan. 6. Receptors controlling
      noradrenaline release could be further discriminated from those controlling
      dopamine and GABA release by very high sensitivity to magnesium and MK-801 and to
      the glycine antagonist L-689,560 but not to other glycine antagonists (CNQX,
      DNQX, 7-Chlorokynurenate, HA-966). 7. Many other individual drug or receptor
      differences were noted. The different profiles observed suggest a wide diversity
      of native NMDA receptors with different properties and an unexpectedly rich
      pharmacopeia of subtype selective antagonists of native NMDA receptors. 8.
      Matching subtype selectivity to particular behavioural effects may be possible
      and the design of subtype selective NMDA antagonists for particular clinical
      applications while avoiding side effect generation seems to be feasible.

PMID- 9533167
TI  - Clinical application of time-dependent sensitization to antidepressant therapy.
AB  - 1. A number of animal studies have shown that the actions of numerous drugs can
      grow or sensitize with the passage of time following even a single treatment, to
      achieve results equal to or greater than those seen after chronic administration.
      2. Our laboratory earlier proposed that this principle might be applied to the
      treatment of human disorders. It was suggested that the same results might be
      achieved by giving drugs once every one or two weeks rather than daily, or, even
      more likely, several-times-daily. 3. Here the authors review the clinical
      literature relevant to that hypothesis, as it relates to antidepressant
      therapies. 4. The evidence uniformly supports our earlier thesis that the
      therapeutic influence of antidepressants would grow with the passage of time,
      even as their pharmacokinetic actions are declining.

PMID- 9533168
TI  - Peripheral blood lymphocytes of bipolar affective patients have a histone
      synthetic profile indicative of an active cell state.
AB  - 1. Although abnormalities of the immune system have been described in depression,
      no information exists regarding the biochemical parameters which could
      characterize the physiological state of lymphocytes from patients with bipolar
      affective disorder. 2. Lymphocytes of normal control subjects are known to be in
      the Go resting phase of the cell cycle. Histone synthesis is characteristically
      different during the Go, G1/G2 and the S phases of the cell cycle. As such, it
      can be used as a biochemical marker with which to distinguish between cycling and
      noncycling cells. 3. In order to investigate the possibility of whether or not
      the lymphocytes of patients with bipolar affective disorder are in an activated
      state, typical of cycling cells, total histone and histone variant synthesis were
      analysed in peripheral blood lymphocytes of a group of 12 patients with bipolar
      affective disorder and 7 normal controls. 4. According to the histone variant
      synthesis pattern, lymphocytes of patients in normothymia have values similar to
      those of controls, i.e., of noncycling cells, while patients in either the
      depressed or the manic phase have values intermediate to those of resting and
      cycling cells. 5. This study shows that histone synthesis can perhaps be used as
      a biochemical parameter of possible significance in differentiating amongst the
      three phases of the illness.

PMID- 9533169
TI  - Anxiolytic effects of low-dose clomipramine in highly anxious healthy volunteers
      assessed by frontal midline theta activity.
AB  - 1. The appearance of Fm theta, the distinct EEG theta rhythm in the frontal
      midline area during performance of a mental task, reflects relief from anxiety in
      humans. 2. In the present study, the anxiolytic effects of low-dose clomipramine
      were examined by monitoring the Fm theta amount, the STAI scores and the plasma 5
      HIAA concentration in 24 male university students with (Fm theta group, n = 12)
      and without (non-Fm theta group, n = 12) Fm theta. 3. Subjects were given
      placebo, 10 mg and 30 mg clomipramine in a double-blind crossover design. Blood
      samples were obtained, STAI scores were determined, and EEGs were recorded before
      and during the performance of an arithmetic addition task. The test was repeated
      twice: before and 3 hrs after drug administration. 4. In the non-Fm theta group,
      10 mg clomipramine decreased the 5-HIAA concentration and state anxiety scores
      but increased the Fm theta amount, while 30 mg clomipramine slightly increased
      only the Fm theta amount. However, there were no differences in these items
      before and after clomipramine administration in the Fm theta group. 5. These
      results suggest that low doses of clomipramine such as 10 mg may exert anxiolytic
      effects during the acute phase of treatment in highly anxious humans.

PMID- 9533170
TI  - Facilitatory effects of chronically administered citicoline on learning and
      memory processes in the dog.
AB  - 1. Citicoline (cytidine (5') diphosphocholine) has been shown to reverse aging
      induced memory deficits, scopolamine-induced amnesia and nucleus basalis
      magnocellularis lesion-induced learning impairment. 2. This study aimed to
      evaluate the effects of citicoline on learning and retrieval processes in a
      complex differential reinforcement of response duration schedule in normal dogs.
      3. The effects of citicoline on a stabilized performance were also measured in
      order to be able to differentiate specific memory effects from non specific
      influences on the motor, neuro-vegetative and motivational systems. 4. The
      results demonstrate that citicoline can exert facilitatory effects on learning
      and memory but also on retrieval processes. The complete absence of effects on
      the stabilized performance and on the motor, neuro-vegetative and motivational
      systems constitutes arguments in favour of a selectivity of action on the memory
      processes.

PMID- 9533171
TI  - Effects of phencyclidine (PCP) and (+)MK-801 on sensorimotor gating in CD-1 mice.
AB  - 1. Male CD-1 mice were tested for prepulse inhibition (PPI) following
      administration of PCP and the PCP site ligand, (+)MK-801, as well as the dopamine
      (DA) agonist (-)-apomorphine and DA releaser d-amphetamine. Similar to reports in
      rats, PCP (0.36-36.0 mumol/kg), (+)MK-801 (0.03-3.0 mumol/kg), (-)-apomorphine
      (3.3 and 10.0 mumol/kg) and d-amphetamine (3.0 and 8.0 mumol/kg) significantly
      reduced PPI when administered prior to testing. 2. Because PCP also binds to
      sigma receptors, the authors tested the sigma ligand (+)-3-PPP at (118 mumol/kg)
      which marginally increased the PPI. 3. Haloperidol (1.1 mumol/kg) pretreatment
      attenuated the reduction in PPI following (-)-apomorphine (10.0 mumol/kg),
      however no effects of haloperidol or clozapine pretreatment on (+)MK-801
      disruption of PPI were observed. 4. Because of the pharmacological similarities
      between mouse data and previously published rat data, it is concluded that the
      mouse is a viable alternative to the rat for testing PPI.

PMID- 9533172
TI  - Pinch-induced catalepsy in mice: a useful model to investigate antidepressant or
      anxiolytic drugs.
AB  - 1. Repeated pinching at the scruff produces, in experimental test/retest
      sessions, prolonged cataleptic-like immobility in mice that may mimic
      immobilities seen in some natural situations. 2. In the first experiment, on male
      mice, imipramine and amitriptiline (20 and 30 mg/kg i.p.) augmented the number of
      pinches necessary to reach the criterion of induced catalepsy and reduced the
      total time of catalepsy. 3. In the second experiment, on female mice, compounds
      that modulate the central 5-HT transmission, like fluvoxamine, fluoxetine (20
      mg/kg i.p.) and ondansetron (0.1 and 1 mg/kg i.p.), retarded the occurrence and
      shortened the duration of pinch induced catalepsy at doses that did not modify
      the open field performances. Maprotiline (a selective inhibitor of the NA
      reuptake) did not modify the mice's performances in respect to controls. 4.
      Female mice presented a more rapid occurrence and a prolonged duration of pinch
      induced catalepsy in respect to male controls. The present behavioral test may
      become a simple experimental model to detect new antidepressant or anxiolytic
      compounds and the significant sex difference could make the test a more useful
      tool in investigating anxiety behaviour in rodents.

PMID- 9533174
TI  - Lesion of the cerebellar interpositus nucleus or the red nucleus affects
      classically conditioned neuronal activity in the hippocampus.
AB  - 1. The cerebellum and the hippocampus have been known to be neural structures
      involved in classical conditioning of the nictitating membrane response in
      rabbits. The neuronal activities related to conditioning are observed in both
      structures. It is uncertain, however, whether these conditioning-related neuronal
      activities are established in parallel or hierarchically. 2. The present study
      was conducted to observe the effects of lesions of the cerebellar interpositus
      nucleus(INT) or the red nucleus(RN) on conditioned hippocampal neuronal activity.
      3. Rabbits in the first experiment were trained by standard delay conditioning
      and then given INT lesion by injecting the kainic acid through a cannula
      previously implanted. Lesions of INT abolished conditioned neuronal responses in
      the hippocampal CA1 area, which had been established before lesioning, as well as
      behavioral conditioned responses(CRs). 4. The second experiment was to examine if
      conditioning-related activities in the hippocampus would develop after RN was
      lesioned with INT intact. Rabbits were first given unilateral electrolytic
      lesions of RN followed by conditioning sessions. Besides a few CRs, they failed
      to show an increase in hippocampal CA1 activity. When training was switched to
      the contralateral eye, animals showed robust CRs and hippocampal responses
      immediately. However, training reswitched to the original eye, behavioral and
      neuronal responses disappeared again. 5. These results suggest that conditioned
      neuronal activities in the hippocampus depends on the cerebellum and that
      conditioning-related inputs from INT via RN may be critical for these conditioned
      neuronal response in the hippocampus.

PMID- 9533173
TI  - Stress-dependent antinociceptive effects of carbamazepine: a study in stressed
      and nonstressed rats.
AB  - 1. The present study examined the antinociceptive effects of carbamazepine on the
      tail flick test in stressed and nonstressed rats. 2. Carbamazepine produced a
      bimodal antinociceptive effect in stressed rats, the first peak appearing 30 min
      and the second 4 h after injection. Antinociceptive effect was not observed in
      nonstressed rats. 3. The secondary, but not the initial, carbamazepine
      antinociception in stressed rats was blocked by naloxone (0.2 mg/kg, i.p.), an
      opioid receptor antagonist. 4. Caffeine (5 mg/kg, i.p.), an adenosine A1/A2
      receptor antagonist, inhibited the both initial and secondary antinociceptive
      effects of carbamazepine in stressed rats. 5. Carbamazepine increased the
      antinociceptive effect induced by either i.p. or i.c.v. administration of N6
      cyclohexyl adenosine (CHA), an adenosine A1 receptor agonist, in stressed rats,
      but decreased it in nonstressed rats. 6. These results suggest that the initial
      antinociceptive effect of carbamazepine in stressed rats may be produced via an
      activation of the adenosine A1 receptors, such as was produced by CHA. The
      secondary long-lasting antinociceptive effects of carbamazepine may be mediated
      by an activation of opioid systems. 7. Furthermore, the initial activation of the
      adenosine A1 receptors by carbamazepine may be a triggering factor for the
      subsequent long-lasting activation of the opioid system, which results in the
      antinociception effects.

PMID- 9533175
TI  - Mechanism of the neuroleptic-induced obesity in female rats.
AB  - 1. Obesity is an undesirable side effect of neuroleptics which affects 50%
      approximately of patients under a program of chronic administration. 2. An animal
      model of neuroleptic-induced obesity and hyperphagia has been developed in female
      rats treated chronically with sulpiride (20 mg/Kg/ip. for 21 days). However, it
      is unknown whether or not the hyperphagia is essential for the development of
      this type of obesity. 3. Sulpiride or vehicle was administered in two
      experimental conditions: in the first one, food was available in an amount which
      was three times the previous individual daily food intake; in the second one, the
      daily food provision was maintained at the individual daily average before
      starting the treatments. This way hyperphagia was prevented in half of the
      groups. Besides the body weight gain measurement in all the groups, the serum
      levels of estradiol, prolactin, glucose and lipids were assessed in the groups
      with unrestricted food intake. 4. Food restriction prevented the sulpiride
      induced weight gain, even though the rats displayed a permanent diestrus which
      suggests an hyperprolactinemia-induced impairment in the balance of the
      reproductive hormones that may promote weight gain. However, the basal levels of
      estradiol were not affected by sulpiride. 5. The high density cholesterol was
      significantly increased by sulpiride, and the serum glucose levels were
      significantly decreased, however these changes were only detected during the
      first week of treatment. 6. The decrease in the serum glucose levels may be an
      early consequence of hyperinsulinemia. 7. Neuroleptic-induced obesity in rats
      appears to mimic energy intake, endocrine status and carbohydrate metabolism in
      humans under chronic neuroleptic administration. However, these rodents did not
      display the typical changes in blood lipids observed in human obesity.

PMID- 9533176
TI  - The effects of flumazenil on focal, electroinduced after-discharge in rabbits.
AB  - 1. The anticonvulsive efficacy of flumazenil 10 mg/kg i.v., a BDZ antagonist, was
      studied in two models of experimental epilepsy electrically induced. 2. The EEG
      after-discharge, which was induced by the electrical stimulation of selected
      brain regions [(notably the dorsal hippocampus (Hip) and the amygdala (CAm)] was
      evaluated in rabbits pre- and post-drug administration. 3. In the animals
      submitted to electrical stimulation of the amygdala, flumazenil exerted a
      protective action, thereby inducing an increase in the after-discharge threshold
      and/or a decrease in after-discharge duration. 4. In the animals submitted to
      electrical stimulation of the hippocampus, flumazenil did not induced changes
      statistically significant. 5. Finally, the paper discusses the two possible
      mechanisms of action of flumazenil (a "per se" partial BDZ activity and/or a BDZ
      agonistic activity, which displaces the inverse agonist-like ligand) and the
      differencies in GABA distribution in the hippocampus and the amygdala.

PMID- 9533177
TI  - Effects of piracetam on the performance of rats in a delayed match-to-position
      task.
AB  - 1. The influence of acute and chronic treatment with piracetam on spatial working
      memory of rats was examined. A new version of an operant chamber "delayed match
      to-position task" was used, in which the animals had to visit one randomly baited
      box out of three boxes ("choice boxes") in a front panel. Hereafter a delay
      period began, in which the subjects had to visit an alcove in the back panel
      ("reference box"). At the end of the delay the animals should return to the front
      panel and choose the same choice box that was baited before the delay, thereby
      obtaining a reward. 2. Rats were trained to a stable level of performance,
      measured as per cent correct responses during sessions of 20 trials.
      Additionally, the time spent between leaving the choice box and entering the
      reference box was recorded. Results were obtained from a single group of rats
      tested repeatedly under different experimental conditions. 3. Injections of
      scopolamine (0.6 mg/kg) significantly reduced the percentage of correct choices
      and increased the time spent to reach the reference box. The impairment of
      correct choices was reversed after chronic treatment with piracetam (250 mg/kg).
      However, the same treatment did not reverse the effect of scopolamine on the time
      performance. 4. Scopolamine also induced an increase of repetitive errors (a
      measure of perseverance), and the chronic treatment with piracetam caused full
      reversal of this increase. These results represent the first observation of a
      piracetam induced reversal of scopolamine impairments in a working memory test.
      5. In normal animals not treated with scopolamine, acute injection of piracetam
      had no effect compared to saline injected controls, but chronic treatment with
      the nootropic significantly enhanced working memory performance. The drug did not
      affect the time used to reach the reference box.

PMID- 9533178
TI  - Establishing orally self-administered cocaine as a reinforcer in rats using home
      cage pre-exposure.
AB  - 1. Rats were force-exposed to a cocaine + saccharin solution in their home cage
      water bottles for five days. They were then given 5 h home-cage access to both
      cocaine and cocaine-free solutions for 40 days. 2. The subjects consumed large
      doses of the cocaine solution despite the ad libitum availability of water. 3.
      The animals were then trained on a task consisting of operant bar pressing
      rewarded on an intermittent schedule with a liquid cocaine reinforcer. 4. All
      subjects performed the operant task and consumed doses of cocaine solution which
      are preferred over water in other paradigms. 5. Levels of responding were
      significantly reduced in three of four subjects when vehicle was substituted for
      liquid cocaine as the reward. 6. This demonstrates that orally self-administered
      cocaine can be used as a reinforcer in rats.

PMID- 9533179
TI  - Delusions of oral parasitosis.
AB  - 1. The authors present a case of a 76-year-old man with delusional disorders,
      somatic type, who strongly believed that his mouth was infested with worms. 2.
      Such a case has not previously been described in the literature and the authors
      refer to the syndrome as delusions of oral parasitosis. 3. The authors examined
      the effect of pimozide, whose efficacy on delusional skin parasitosis has been
      proven. Taking the neuroleptic at a dose of 2 mg daily relieved the symptoms.

PMID- 9533180
TI  - The isoprostanes: a perspective.
AB  - The isoprostanes are a new class of natural products produced in vivo by a non
      enzymatic free-radical-induced peroxidation of polyunsaturated fatty acid. In the
      case of arachidonic acid, for example, four classes of isoprostanes can be
      produced. Because of the specific structural features distinguishing them from
      other free-radical-generated products, e.g., HETEs, etc., the isoprostanes can
      provide an exclusive and selective index for the oxidant component of several
      inflammatory and degenerative diseases. The possible mechanisms of formation of
      the individual isoprostanes is discussed in detail. Class III products, such as 8
      iso-PGF2 alpha and 8-iso-PGE2 have been shown to be vasoconstrictors and modulate
      platelet function. Several synthetic representatives from the four classes of
      arachidonic-acid-derived isoprostanes have already been prepared by total
      synthesis. These synthetic standards have been used for the identification and
      quantitation of these isoprostanes in biological fluids using gas
      chromatography/mass spectrometry methodology.

PMID- 9533181
TI  - Nomenclature of isoprostanes: a proposal.
AB  - We have proposed a nomenclature system for the isoprostanes, a new class of
      natural products formed in vivo by the free-radical peroxidation of
      polyunsaturated fatty acids. Our proposed nomenclature is based on the assignment
      of four isoprostanes, 1, 9, 17, and 25, as representatives of the four classes of
      isoprostanes derived from arachidonic acid (AA). We have attempted as much as
      possible to retain elements from the familiar prostaglandin nomenclature. In this
      proposal, we have used the abbreviation i.p. for isoprostane. We have classified
      isoprostane classes or types based on omega-carbon as being the starting
      reference. Roman numerals I-VI refer the six types of isoprostanes derived from
      eicosapentaenoic acid (EPA) and III-VI refer to the four types derived from AA.
      This nomenclature can be applied to isoprostanes derived from other PUFAs also.

PMID- 9533183
TI  - Urinary thromboxane B2 in cardiac transplant patients as a screening method of
      rejection.
AB  - Noninvasive methods for regular monitoring of cardiac transplant patients for
      acute rejection are preferable to the only currently accepted method involving
      frequent endomyocardial biopsies. Thromboxane A2 (TXA2) is synthesized in large
      amounts by monocytes/macrophages during organ graft rejection. It enhances T
      lymphocyte clonal expansion and cytotoxic function as well as upregulating the
      major histocompatibility class II expression on antigen presenting cells.
      Experimentally increased urinary excretion of TXA2 metabolites is associated with
      cardiac transplant rejection. We therefore compared urinary immunoreactive
      thromboxane B2 (i-TXB2) levels to the rejection score of the endomyocardial
      biopsies. In addition we graded the degree of activated lymphocytes in peripheral
      blood. Urinary i-TXB2 was significantly higher in patients exhibiting medium to
      severe rejection than in patients without rejection (1236 +/- 372 vs. 526 +/- 57
      pg/mL). The urine i-TXB2 (704 +/- 48 pg/mL) of all patients who participated in
      this study, whose endomyocardial biopsy indicated rejection, was also
      significantly higher than in the non-rejecting group. Increased levels of urine i
      TXB2 were associated with increased biopsy scores. Circulating activated
      lymphocytes was also significantly increased in patients with moderate/severe
      rejection compared to patients with no rejection (66 +/- 11 vs. 39 +/- 4 per mm
      (3)) (p < 0.01). Further, this study shows that urine i-TXB2 is associated with
      increased endomyocardial biopsy scores (acute rejection scores) and blood
      lymphocyte activation. Thus we conclude that urine i-TXB2 may be of potential
      value as a diagnostic screening test for helping identify cardiac transplant
      patients undergoing acute rejection.

PMID- 9533182
TI  - Occurrence of 13(S)-hydroxyoctadecadienoic acid in biological samples.
AB  - The oxygenated metabolite of linoleic acid, 13(S)-hydroxyoctadecadienoic acid has
      recently been shown to play a role in cellular regulation. To detect this
      molecule in biological systems, we recently developed a specific polyclonal
      antibody. Using this antibody, we report the presence of 13(S)
      hydroxyoctadecadienoic acid in human urine, cell culture media, and untreated
      goat serum for the first time by a specific, sensitive, and rapid enzyme
      immunoassay. Furthermore, the enzyme linked immunosorbent assay data are verified
      by gas chromatography/mass spectrometry analysis of the same samples.

PMID- 9533184
TI  - Tomoxiprole selectively inhibits cyclooxygenase-2.
AB  - Tomoxiprole is a nonsteroidal anti-inflammatory compound that was reported to
      have low ulcerogenic potential, a quality that would be expected of a
      cyclooxygenase-2-selective inhibitor, and, in fact, we find it is selective for
      this isozyme. In stably transfected COS cells, the compound inhibits recombinant
      human cyclooxygenase-2 (IC50 = 7 nM) more potently than recombinant
      cyclooxygenase-1 (IC50 = 240 nM), and similar results are obtained with partially
      pure ovine enzyme preparations. The compound is thus a very potent as well as
      selective inhibitor of cyclooxygenase-2. As is true of some other cyclooxygenase
      2-selective inhibitors, tomoxiprole inhibition of cyclooxygenase-2 but not
      cyclooxygenase-1 is time-dependent.

PMID- 9533185
TI  - Temporal memory for remote events in healthy aging and dementia.
AB  - Memory for the temporal order of term of office of 7 past U.S. presidents was
      examined in healthy older adults and individuals in the early stages of dementia
      of the Alzheimer type (DAT). Among those individuals who recognized all 7
      presidents, bow-shaped serial-position effects for temporal order similar to
      those seen in studies of short-term memory were observed for both the healthy
      group and the groups of individuals with dementia. Accuracy of temporal ordering
      decreased with increasing dementia severity. Thus, DAT affects 1 aspect of "old"
      memory (i.e., temporal information) even in the very early stages of the disease.
      Theoretical models of serial-position effects need to address remote memory as
      well as short-term memory.

PMID- 9533186
TI  - Longitudinal invariance of adult psychometric ability factor structures across 7
      years.
AB  - The hypothesis that psychometric ability tests retain equivalent factor
      structures across a 7-year interval was examined in a sample of 984 persons
      (disaggregated into 6 cohort groups: M ages at first test = 32, 46, 53, 60, 67,
      and 76), assessed in 1984 and 1991 as part of the Seattle Longitudinal Study. A
      best fitting measurement model was estimated for 20 psychometric tests marking
      the 6 primary abilities of Inductive Reasoning, Spatial Orientation, Perceptual
      Speed, Numeric Facility, Verbal Ability, and Verbal Recall. Gender was partialed
      out at the variable level by including a gender factor. Weak factorial invariance
      over time was demonstrated for all cohorts. Configural invariance could be
      demonstrated across all cohort groups. However, weak factorial invariance across
      groups could be accepted for all but the youngest and oldest groups. Latent means
      were modeled for the accepted solutions across time and cohort groups.

PMID- 9533187
TI  - Age differences in context integration in memory.
AB  - This research examined the role of contextual integration in memories of younger
      and older adults. In 2 experiments, recall of a target picture to a context
      picture cue was better when sentences were generated that integrated the picture
      pair and when the picture pairs were already related to each other. Age
      differences were smallest when sentences were generated for semantically related
      pairs. Older adults generated the same type sentences as younger adults, although
      they generated fewer integrations for unrelated pairs. In a 3rd experiment,
      younger adults could not differentiate between younger- and older-generated
      sentences from Experiment 1, and the sentences did not differentially affect
      recall performance. The results are discussed in terms of age differences in self
      initiated processing when using context.

PMID- 9533188
TI  - The role of problem definitions in understanding age and context effects on
      strategies for solving everyday problems.
AB  - The participants (107 preadolescents, 124 college students, 118 middle-aged
      adults, and 131 older adults) described 2 everyday problems (1 unconstrained, the
      other constrained to 1 of 6 domains) that they experienced and their goals and
      strategies. Problem definitions reflected interpersonal or competence components
      or both; strategies reflected altering cognitions, actions, or regulating and
      including others. Age differences in problem definitions were found. For
      unconstrained-domain problems, age and problem definition were related to
      strategies; for unconstrained-domain problems age differences in strategies were
      not found. For constrained-domain problems, strategies related to problem domain
      and problem definition, with problem definition the better predictor of
      strategies. The results illustrate the value of individuals' problem definitions
      for addressing age and context effects on strategies used.

PMID- 9533189
TI  - Practical intelligence at work: relationship between aging and cognitive
      efficiency among managers in a bank environment.
AB  - A study was conducted to determine which better predicts performance among bank
      managers: tacit practical knowledge as assessed by the Tacit Knowledge Inventory
      for Managers (TKIM) or 2 psychometric measures of reasoning, the Raven's Advanced
      Progressive Matrices (Raven's) and the Verbal Reasoning subtest of the
      Differential Aptitude Test (DAT). Two hundred bank managers (43 experts and 157
      nonexperts), ages 24-59 years old, participated. Increased age was associated
      with lower performance in Raven's and the DAT but less so in the TKIM; best
      performing older managers on average had high levels of tacit knowledge, although
      they scored lower on psychometric reasoning measures; TKIM predicted managerial
      skill; DAT and Raven's did not. These results suggest that stabilization of some
      aspects of intelligence may occur in old age. Implications of the findings for
      the study of practical intelligence, expertise, and compensatory abilities are
      discussed.

PMID- 9533190
TI  - Financial strain, received support, anticipated support, and depressive symptoms
      in the People's Republic of China.
AB  - The purpose of this study is to examine the interface between financial strain,
      informal received economic support, informal anticipated financial support, and
      psychological distress in later life. Data provided by a large probability sample
      of older adults in the People's Republic of China reveal that the relationship
      between financial difficulty and psychological distress is stronger for older
      adults who receive more economic assistance. However, the results involving
      anticipated support are in the opposite direction. More specifically, the
      association between financial problems and psychological distress is lower for
      older adults who believe that others stand ready to help in the future should the
      need arise. A detailed theoretical rationale is developed to explain these
      results.

PMID- 9533191
TI  - Narrative comprehension and aging: the fate of completed goal information.
AB  - Previous research has shown that older adults are able to use situation models in
      a manner similar to younger adults. However, other areas of cognition have shown
      that older adults are less able to remove irrelevant information from the current
      stream of processing. Accordingly, the authors tested whether older and younger
      adults would differ in reducing the availability of information about a completed
      goal in a situation model during narrative comprehension. In 2 experiments,
      memory probes tested for the availability of protagonist goal information during
      reading when it was either failed goal, completed goal, or neutral information.
      The results for both age groups showed that goal information was most available
      in the failed goal condition, less available in the completed goal condition, and
      least available in the neutral condition. No reliable differences between younger
      and older adults in the pattern of response times were observed. Reading time
      data were also examined to explore the possibility that older adults engage in a
      longer wrap-up period after a goal is completed, but no such difference was
      found.

PMID- 9533192
TI  - Three-year changes in cognitive performance as a function of apolipoprotein E
      genotype: evidence from very old adults without dementia.
AB  - This study examined whether baseline cognitive performance and 3-year
      longitudinal changes were influenced by apolipoprotein E epsilon 4 (APOE-epsilon
      4) allele. Participants consisted of 20 APOE-epsilon 4 (2 epsilon 2/epsilon 4; 17
      epsilon 3/epsilon 4; 1 epsilon 4/epsilon 4) and 54 non-epsilon 4 (12 epsilon
      2/epsilon 3; 42 epsilon 3/epsilon 3) very old adults without dementia (M = 81.82
      +/- 5.06 years) participating in a population-based longitudinal study. Cognitive
      performance was indexed by the Mini-Mental State Examination and multiple indexes
      of memory, visuospatial, and verbal performance. The results indicated no
      significant baseline differences between the 2 APOE groups in any cognitive
      performance measure. However, analyses revealed that the APOE-epsilon 4 group
      experienced greater negative change in recognition memory for faces and words.
      Changes in tasks assessing other abilities did not vary as a function of APOE
      status. The authors concluded that APOE-epsilon 4 status may not influence
      cognitive performance in adults without dementia and speculated that when such
      effects do occur (e.g., decline in recognition memory), these may be related to
      impending dementia, rather than to the influence of the specific genotype on
      cognition in normal aging.

PMID- 9533193
TI  - Repetition priming in normal aging and Alzheimer's disease: a review of findings
      and theories.
AB  - On repetition priming tasks, memory is measured indirectly as a change in
      performance due to recent experience. It is often functionally and neurally
      dissociated from performance on explicit memory tasks, which directly measure
      conscious recall or recognition of recent events. Repetition priming has
      therefore been extensively studied in normal aging and Alzheimer's disease, which
      feature mild to severe changes in explicit memory. Initial studies indicated that
      repetition priming was immune to the effects of aging and greatly reduced in
      Alzheimer's disease (AD). As more studies have been performed, however, these
      initial conclusions appear less clear than before and, in the case of AD,
      actually misleading. The purpose of this article is to provide a comprehensive
      review of this rapidly expanding literature, articulate the issues that are
      critical to interpreting the empirical results, and discuss what new conclusions
      are suggested by the overall pattern of findings.

PMID- 9533194
TI  - Aging and the Stroop effect: a meta-analysis.
AB  - In this meta-analysis, data from 20 studies comparing younger and older adults on
      the Stroop interference effect, contained in 15 articles, were analyzed. No
      significant difference was found in the Stroop interference effect, expressed as
      mean standardized difference, between the 2 age groups (for younger adults: d =
      2.04; for older adults: d = 2.17). Moderator variables were present, but these
      did not produce age differences. Brinley analysis showed that a single regression
      line with a slowing factor of 1.9 described the data well (R2 = .83) and
      confirmed that no Age x Condition interaction was present in the data. Likewise,
      no Age x Condition interaction was found when the data were fitted to the
      information loss model; the age ratio of decay rates was estimated to be 1.4.
      Consequently, the apparent age-sensitivity of the Stroop interference effect
      appears to be merely an artifact of general slowing.

PMID- 9533195
TI  - Age-related priming effects in social judgments.
AB  - Two experiments investigated adult age differences in the impact of previously
      activated (and thus easily accessible) trait-related information on judgments
      about people. The authors hypothesized that age-related declines in the
      efficiency of controlled processing mechanisms during adulthood would be
      associated with increased susceptibility to judgment biases associated with such
      information. In each study, different-aged adults made impression judgments about
      a target, and assimilation of these judgments to trait constructs activated in a
      previous, unrelated task were examined. Consistent with the authors' hypotheses,
      older adults were likely to form impressions that were biased toward the primed
      trait constructs. In contrast, younger adults exhibited greater awareness of the
      primed information and were more likely to correct for its perceived influence,
      especially when distinctive contextual cues regarding the source of the primes
      were available.

PMID- 9533196
TI  - Time course of allocation of visual attention after equating for sensory
      differences: an age-related perspective.
AB  - Adult age differences in the time course of the allocation of visual attention
      were investigated, in 2 experiments that both included the same 10 younger adults
      (M = 22 years) and 10 older adults (M = 68 years). In Experiment 1, older adults
      accumulated information about target identity at a slower rate than younger
      adults, as represented by the rise in accuracy as a function of target duration.
      To equate performance in a baseline condition in a spatial-cuing paradigm
      (Experiment 2), target duration was set for each observer on the basis of the
      data in Experiment 1. Performance for the 2 age groups was comparable, both in
      the baseline condition and in the time course of attention, as indexed by the
      function relating accuracy to cue-target onset asynchrony. The authors conclude
      that, in this spatial-cuing paradigm, an age-related change is evident in sensory
      processing but not in attentional allocation.

PMID- 9533197
TI  - Quality of the caregiver--care recipient relationship: does it offset negative
      consequences of caregiving for family caregivers?
AB  - This study examined whether relationship quality mediates, moderates, or both
      mediates and moderates the associations between caregiving stressors (e.g.,
      disability and behavioral problems) and negative consequences associated with
      caregiver well-being (overload, role captivity, and depression). Data on family
      (spouses and children) caregivers (n = 118) came from a longitudinal study of a
      representative sample of disabled older people and their primary caregivers.
      Relationship quality mediated the linkages between the presence of problem
      behaviors and the outcomes of role captivity and depression. That is, when
      problem behaviors were present, they related to higher levels of captivity and
      depression because quality of the relationship suffered. Relationship quality
      moderated the linkage between disability and overload. Specifically, for those
      with a higher quality of relationship, increased disability was related to higher
      levels of perceived overload.

PMID- 9533198
TI  - Objective sleep measures and subjective sleep satisfaction: how do older adults
      with insomnia define a good night's sleep?
AB  - The relationship between objective sleep measures and subjective sleep
      satisfaction was explored in a sample of 47 older adults (59 years and older; 35
      women, 12 men) with primary insomnia. Participants submitted to all-night sleep
      evaluations (polysomnography) for 2 nights. After each night, participants
      provided subjective sleep-satisfaction ratings. Depth of sleep (decreased Stage 1
      sleep and increased Stages 3 and 4 sleep) and sleep latency were the best
      predictors of subjective sleep satisfaction. For other sleep variables such as
      sleep efficiency and wake time after sleep onset, no value predicted satisfaction
      on a particular night. However, for these sleep variables, relative improvement
      from Night 1 to Night 2 predicted greater subjective satisfaction.

PMID- 9533199
TI  - Constraints on general slowing: a meta-analysis using hierarchical linear models
      with random coefficients.
AB  - General slowing (GS) theories are often tested by meta-analysis that model mean
      latencies of older adults as a function of mean latencies of younger adults.
      Ordinary least squares (OLS) regression is inappropriate for this purpose because
      it fails to account for the nested structure of multitask response time (RT)
      data. Hierarchical linear models (HLM) are an alternative method for analyzing
      such data. OLS analysis of data from 21 studies that used iterative cognitive
      tasks supported GS; however, HLM analysis demonstrated significant variance in
      slowing across experimental tasks and a process-specific effect by showing less
      slowing for memory scanning than for visual-search and mental-rotation tasks. The
      authors conclude that HLM is more suitable than OLS methods for meta-analyses of
      RT data and for testing GS theories.

PMID- 9533200
TI  - [Information about the diagnosis: a subjective experience of patients with
      multiple sclerosis and rheumatoid arthritis].
AB  - INTRODUCTION: It may be difficult to determine the adequate mement, the
      information content and the most convenient person to inform patients with
      chronic, incurable disorders with uncertain prognosis as sclerosis multiple (MS).
      MATERIAL AND METHODS: To gain information on how these aspects had been carried
      out and the extent to which patients felt satisfied, we studied 60 definite MS
      ambulatory patients by means of a semistructured questionnaire attending a
      hospital-based MS unit. The results were compared with those from 40 patients
      with rheumatoid arthritis (RA), a chronic disabling disorder of the locomotor
      system with variable course, examined in a similar way. RESULTS: In the vast
      majority of patients (81.7 and 82.9%, respectively) in both groups the diagnosis
      had been delivered by a specialist, a point on which most patients agreed upon as
      convenient. However, most MS patients (78.4%) and nearly all of those with RA
      (97.6%) should have desired to receive information on their diagnosis as soon as
      this might had been firmly established. Though more than half the patients (61.7
      of MS and 56.1% of RA) admitted to have developed depressive symptoms following
      information on their diagnosis, a majority expressed their desire to have been
      informed early about 'all the truth' regarding their prognosis (78.4 and 87.8%,
      respectively). CONCLUSIONS: Though data from this study should be taken with
      caution when applied to MS patients shortly after experiencing their first
      symptoms, and it is therefore unwise to give rigid rules, the vast majority of MS
      patients express the desire to receive early, accurate, and individualized
      information on their diagnosis provided by a competent specialist.

PMID- 9533202
TI  - [Epidemiology of Haemophilus influenzae type b, Neisseria meningitidis, and
      Streptococcus pneumoniae in children in the Valencia Community, Spain. Acute
      diseases study group].
AB  - OBJECTIVE: To asses the incidence of Haemophilus influenzae type b (Hib),
      Neisseria meningitidis and Streptococcus pneumoniae meningitis in children of de
      Valencian Community (VC), Spain, and to describe the microbiologic
      characteristics. MATERIAL AND METHODS: Prospective surveillance system with
      paediatrician and microbiologist participation of all public hospitals of the VC.
      Cases are children less than 15 with clinical meningitis and with isolation of
      Hib, N. meningitidis or S. pneumoniae from CSF of blood. RESULTS: From 1st
      December 1995 to 30th November 1996, 51 cases were declared, 33.3% were Hib,
      49.0% N. meningitidis and 17.7% S. pneumoniae. The annual incidence of meningitis
      was 7.6 cases/100,000 < 15 years, 20.5/100,000 < 5 years and 56.2/100,000 < 1
      year. 84.3% of the cases occurred in children younger than 5. S. pneumoniae had
      the highest mortality. CONCLUSIONS: Hib is a frequent cause of meningitis in
      spite of that one third of children are vaccinated. 43% of the N. meningitidis
      isolated in meningitis are serogroup C. S. pneumoniae meningitis are more
      frequent in children less than one, and has a high mortality rate.

PMID- 9533201
TI  - [Indicators of oxidative stress and the effect of antioxidant treatment in
      patients with primary Parkinson disease].
AB  - INTRODUCTION AND OBJECTIVE: Parkinson's disease (PD) is characterized by a
      progressive, slow loss of dopaminergic neurones in the substance nigra. Although
      the cause of this neurone loss is unknown, at the present time many papers
      suggest oxidative stress (OS), secondary to dopaminergic metabolism, as an
      aetiopathogenic factor of PD. Therefore study of the part played by OS in this
      would permit the use of antioxidants (AO) as another possibility for treatment of
      the disease. It would also be a major step forward in the search for possible
      biological markers. MATERIAL AND METHODS: A study using spectrophotometric
      techniques was made of the serum levels of four biochemical indicators: catalase
      (CAT), malonyl aldehyde (MDA), phospholipase A2 (PLA2) and Vitamin C (VITC) in
      controls and in patients with PD. We found the average value for each of the
      variables studied in controls and in patients, taking AO treatment into account.
      RESULTS: The effect of clinical variables on serum levels of CAT, MDA, PLA2 and
      VITC was analyzed. It was seen that only the clinical state of Hoen and Yahr was
      related to the biochemical indicators. The CAT activity and VITC concentration
      showed statistically significant differences between patients (independently of
      their AO treatment) and controls. The CAT activity was significantly less in
      those treated with AO. The patients with PD did not all have the same degree of
      OS. The effect of AO treatment on plasma markers showed changes only in one
      subgroup of Parkinson patients. CONCLUSIONS: Our study suggests that AO treatment
      in this condition should be tailored to the individual patient according to the
      degree of OS present.

PMID- 9533203
TI  - [Respiratory chain and pyruvate metabolism deficiencies in pediatric patients:
      evaluation of biochemical tests for selective screening].
AB  - INTRODUCTION: The correct selection of pediatric patients with clinical suspicion
      of mitochondrial diseases is the first step to achieve a definitive diagnosis.
      MATERIAL AND METHODS: The results of the initial biochemical tests obtained in 35
      children diagnosed of respiratory chain or pyruvate metabolism defects were
      reviewed. The efficiency of basal determinations (lactate, pyruvate, ketone
      bodies, amino and organic acids and carnitine), cerebrospinal fluid (CSF)
      analysis, and dynamic tests (exercise, glucose loading and glucose oxidation by
      lymphocytes) was discussed. RESULTS: Plasma lactate and alanine, and CSF
      metabolites were the most informative measurements in basal status. Urine organic
      acids were very useful to confirm the initial suspicion. Glucose loading was the
      most informative and reliable challenge test for pediatric population, while
      exercise test was especially useful for older children with fatigability or
      peripheral nervous system involvement. CONCLUSIONS: Glucose oxidation by
      lymphocytes might be applied when the other dynamic tests can not be performed or
      are not informative.

PMID- 9533204
TI  - [Epilepsy and disorders of cortical development in children with congenital
      cytomegalovirus infection].
AB  - INTRODUCTION: Neuroimaging and experimental studies have related cytomegalovirus
      (CMV) to certain neuronal migration disorders. MATERIAL AND METHODS: To define
      the electroclinical picture of children with epilepsy associated with disorders
      of cortical development (DCD) and congenital CMV infection, we conducted a
      clinical, electroencephalographic and neuroradiological study of 10 children with
      this condition. RESULTS: Eighty per cent of them had dismorphic traits, or
      malformations outside CNS. All showed other neuroradiological signs (cerebral
      calcification, white matter damage, porencephaly). Six patients with
      bihemispheric DCD (agyria-pachigyria, 2; 'poligyria', 1; schizencephaly, 1;
      bilateral opercular DCD, 2) showed: Tetraparesis, severe or profound mental
      deficiency, early onset epilepsy (mean age at onset: 11 months) with spasms,
      tonic seizures, partial seizures, and multifocal paroxysms or unusual diffuse
      sharp Alfa-Beta EEG activity. One child developed Epilepsia Partialis Continua.
      Children with bilateral opercular DCD evolved to a continuous spike and wave (SW)
      electrical status during wakefulness and sleep, linked to a worsening of
      psychomotor derangement. Four patients with unilateral hemispheric DCD
      (pachigyric or 'poligyric') showed: Congenital hemiparesis, mild intellectual
      deficiency, motor seizures (orofacial, hemiclonic, generalized) beginning in the
      third year of live, atypical absences with focal phenomena, frequent focal
      rhythmic SW discharges during wakefulness, and continuous SW status during sleep
      (CSWS). CONCLUSIONS: A wide spectrum of DCD due to congenital CMV infection is
      documented. Characteristic electroclinical pictures related to the extent and
      topographical distribution of the DCD are recognized, which may lead to an
      appropriate diagnosis and prognosis.

PMID- 9533205
TI  - [Neuromuscular disorders in critically ill patients].
AB  - INTRODUCTION AND OBJECTIVE: Critically ill patients admitted to the Intensive
      Care Unit (ICU) often develop neuromuscular disorders. The objective of this
      study was to diagnose these and determine the causes. MATERIAL AND METHODS: We
      present a series of 13 critically ill patients who developed weakness or paresia,
      reduced or absent ROT and normal brain stem reflexes, in whom ENG and EMG studies
      were done in EESS and II which were considered together with data from general
      laboratory analysis, radiological and microbiological examinations, medication
      given and posterior clinical course of the patient. Muscle biopsy was not done in
      any patient. RESULTS: All the patients were intubated, with signs of sepsis,
      multiple-organ failure and malnutrition. All had received cortico-steroids and
      amino-glucosides and 8/13 neuromuscular blockers. Neurophysiological study showed
      that in all cases there was axon type neuropathy, mainly motor and in the lower
      limbs. Fifty four percent of the patients died. The neuropathy improved in the
      others. CONCLUSIONS: Critically ill patients often have axon type neuropathy. In
      our series, the causes of this were sepsis and multiple organ failure. It is
      important that this pathology be ruled out in the critically ill patient whom it
      is difficult to disintubate and/or has generalized muscle weakness.

PMID- 9533206
TI  - [Prevalence of depressive disorders in dementia].
AB  - OBJECTIVE: To find the prevalence of depressive illness associated with dementia
      in our geriatric population. MATERIAL AND METHODS: A study was made of the entire
      population aged over 69 years in eight rural districts of the province of Girona
      (Spain). Diagnosis was made using CAMDEX criteria. RESULTS: The prevalence of
      depression (depressive disorders plus pseudo dementia) was 9.1% (IC = 7.6-10.5%).
      In the group of patients with dementia, the frequency of depression was 28.15%
      whilst in the group with no dementia it was 5.4% (p = 0.0000). No differences
      were seen in the prevalence of depression between patients with Alzheimer type
      dementia (ATD) and those with vascular dementia (VD). The gravity of dementia,
      sex and age did not influence the frequency of depression. CONCLUSIONS:
      Depression in patients with dementia was very frequent in our geriatric
      population. Dementia was seen to be a risk factor with regard to depression.

PMID- 9533207
TI  - [Ketogenic diet: efficacy and tolerability in childhood intractable epilepsy].
AB  - INTRODUCTION: Prospective study to evaluate efficacy of ketogenic diet (KD) in
      the treatment of children with intractable epilepsies (IE). Tolerability of the
      KD was also considered. MATERIAL AND METHODS: Criteria for inclusion were: 1.
      Epilepsy refractary to treatments with antiepileptic drugs (AED) in monotherapy
      and combining two or three AED. 2. Acknowledgment of blood levels of these drugs
      in therapeutic range. 3. Absence of liver or kidney disease, metabolic
      abnormalities, inborn errors of metabolism or other progressive encephalopathies.
      4. Family supposedly in economic and psychologic conditions to accept the
      difficulties of strictly maintaining KD. We used a classic KD following the
      criteria suggested by the John Hopkins Pediatrics Epilepsy Center. Baseline
      neurological and physical examination, EEG, blood chemistry including lipid
      profile were obtained prior to initiative and during the KD. KD efficacy was
      measured as percent reduction of baseline seizures frequency, considering
      positive results as reductions of 50% or over. Acceptance of the diet and quality
      of life were specially considered. Eighteen patients with ages from 2 to 11 years
      were admitted. Ten of them were males. Diagnosis followed the last Classification
      of Epileptic Syndromes of the ILAE, and distribution was: Symptomatic partial
      epilepsies, 8 cases (one had West syndrome at age 5 months); cryptogenic partial
      epilepsies, 1 case; Lennox-Gastaut syndrome, 2 cases; severe myoclonic epilepsy
      of infancy, 6 cases and epilepsy with myoclonic astatic seizures 1 case. RESULTS:
      Four patients were not able to achieve persistent ketosis either due to patient's
      rejection of KD or to parents non compliance. KD was kept for at least two months
      before considering failures. Five patients did not show significant improvement
      and KD was stopped. At present nine patients have been on KD from 6 to 24 months
      (average 16 months). Four of them showed a 75-100% reduction in seizures
      frequency and in three the reduction was of 50-75%. CONCLUSIONS: KD was fairly
      well tolerated by 14 of 18 children and their families. Fifty percent of the 14
      patients complying KD showed significant improvement in seizure frequency and in
      quality of life. Due to the small number of patients and short follow-up, we can
      not speculate about results in relation to each epileptic syndrome, neither the
      risk of late complications.

PMID- 9533208
TI  - [The effect of cigarettes on somatosensory potentials].
AB  - INTRODUCTION AND OBJECTIVE: The physiological and pathological effects of
      cigarettes on the nervous system have been widely studied, but none of the
      investigations carried out has enabled us to determine the degree to which
      nicotine may affect the central pathways of somatosensorial evoked potentials in
      humans. MATERIAL AND METHODS: Following parameters established internationally
      for investigation of the effects of nicotine on the nervous system, we find that
      the N18 wave obtained by stimulation of the median nerve before smoking
      completely disappears after smoking for 3 minutes and reappears 10 minutes after
      smoking has stopped. CONCLUSIONS: Therefore, we conclude that the action of
      nicotine on these evoked potentials is mainly subcortical, and for this reason it
      is essential to investigate the toxicological history before carrying out any
      clinical or neurophysiological study, since this might affect the results
      obtained.

PMID- 9533209
TI  - [Analytical epidemiological study of multiple sclerosis in Alcoi].
AB  - INTRODUCTION: Multiple sclerosis (MS) is a disease of controversial epidemiology,
      which has frequently been studied. The results of an epidemiological descriptive
      study in the Alcoi area led to a first case-control study to give information
      about the factors associated with the illness in this area. It was seen from this
      that migration, contact with dogs and with cloth might be related to it.
      OBJECTIVE: To carry out a second analytical study, maintaining the migration
      factor stable to avoid the possible confounding effect with other associated
      factors. MATERIAL AND METHODS: For this case-control study we grouped one case
      with four controls from the population according to age, sex and place of birth.
      All cases fulfilled criteria defined for MS and the controls were randomly
      selected from the census. We also classified the cases and controls into three
      groups, according to whether or not migration was involved (group A:
      Autochthonous; group B: Immigrants who arrived before the age of 13, and group C:
      Immigrants who arrived after the age of 13). RESULTS: We analyzed 40 patients and
      160 controls. We obtained significant values for 'social group'. The cases
      belonged to the less favored social group both on overall analysis and in the
      autochthonous group. Pneumonia was the only infection with significant figures in
      patients over 15. Contact with dogs gave new statistically significant figures,
      together with cloth and cloth products. CONCLUSIONS: Persistence of positive
      correlation of MS with contact with dogs and cloth suggest the possible influence
      of these two factors in the increase in incidence of MS in this area.

PMID- 9533210
TI  - [Neurophysiological study in Alpers syndrome].
AB  - INTRODUCTION: Infantil progressive polydystrophy was described by Alpers in a
      child with psychomotor retardation, crises which were resistant to treatment and
      diffuse loss of cortical neurons. OBJECTIVE: The aim of this study was to review
      the neurophysiological aspects of Alpers syndrome and their clinical correlation.
      MATERIAL AND METHODS: We present three children with subacute encephalopathy,
      progressive psychomotor retardation, myoclonic epilepsy which was resistant to
      treatment and crises of apnea, who had degeneration of the cerebral grey matter.
      Serial EEG, polysomnographs, auditory evoked potentials of the brain stem and
      visual evoked potentials were done. RESULTS: The electroencephalogram findings
      showed the presence of complex bursts of acute waves, small many-pointed or slow
      waves of great amplitude which were irregular and arrhythmical, lasting one to
      five seconds, separated by periods of inactivity on the tracing which lasted from
      three to ten seconds. The EEG was distinctive, changing over the course of the
      illness, and with increasing numbers and duration of the bursts of suppression of
      cerebral bioelectric activity. Polysomnography showed cerebral bioelectric
      activity which was markedly unstructured and with little difference between the
      tracings when asleep and when awake, together with a large number of apneas of
      obstructive and mixed types. The PEAT showed reduced amplitude and altered
      morphology in all the waves, and even absence of some of them. The visual evoked
      potentials were asymmetrical and with delay in the latency of the P100 wave.
      CONCLUSIONS: Although definite diagnosis of progressive neurone degeneration
      requires post mortem examination of the brain, clinico-pathological studies,
      including electrophysiological, radiological and biochemical studies are
      sufficiently characteristic to suggest the diagnosis during life.

PMID- 9533211
TI  - [Hypodense meningioma. A care report].
AB  - INTRODUCTION: Meningiomas are benign tumours which originate in the arachnoid
      layer and are characterized by being iso- or hyper-dense on computerized axial
      tomography (CAT). Hypodense meningiomas are relatively infrequent and normally
      behave thus because of their fat content. A hypomeningioma is almost entirely
      composed of adipose tissue. However, a meningiotheliomatous meningioma with fatty
      degeneration, which is the case being considered, is characterized by zones of
      meningiotheliomatous cells together with zones of adipocytes. CLINICAL CASE: We
      present the case of a 73 year old woman with a meningiotheliomatous meningioma
      with extensive fatty degeneration which on CAT scan showed as a hypodense lesion,
      with well-defined edges, which took up contrast heterogeneously and produced a
      hyperosfosant reaction. On magnetic resonance (RMN) it gave signals of
      heterogeneous intensities. Up to the present time, only four cases of pure
      lipomeningiomas have been described in the literature. CONCLUSIONS: However,
      meningiomas with fatty degeneration are much more frequent. In this paper we
      discuss aspects of the differential diagnosis of meningiomas which behave as
      hypodense lesions on CAT scans.

PMID- 9533212
TI  - [West's syndrome associated with inversion duplication of chromosome 15].
AB  - We describe a five year old boy with inversion duplication of chromosome 15 (inv
      dup (15)) who, at the age of six months had started to develop West's syndrome.
      He later developed cryptogenic myoclonic epilepsy which was resistant to
      medication. On examination there was dysmorphia, overall hypotonia and diffuse
      pyramidalism. On starting ACTH the crises of flexion spasms were reduced but
      these were soon followed by myoclonic crises, both tonic and atonic, which did
      not respond to the various anticonvulsive treatments given. We comment on the
      changes in chromosome 15 linked to convulsions, and particularly the phenotypes
      of the inv dup (15) which depend on the size and genetic composition of the
      anomaly. This is the third case described in the literature of a patient with
      West's syndrome associated with supernumerary inversion duplication of chromosome
      15. It is suggested that the karyotype be included when studying convulsive
      encephalopathies and cryptogenic refractory epilepsy, especially in infantile
      spasms.

PMID- 9533213
TI  - ['Rubral' tremor after vascular thalamic lesions].
AB  - INTRODUCTION: The appearance of tremor after thalamic lesions is well-known but
      infrequent. Amongst the semiological varieties of thalamic tremors, a
      particularly uncommon type--which is extremely incapacitating owing to its great
      amplitude, appearance during action and poor therapeutic response--is the so
      called rubric or mesencephalic tremor. CLINICAL CASES: We present four cases, of
      tremor with the semiological characteristics of rubric tremors after thalamic
      lesions of ischaemic or haemorrhagic origin. We review the relevant literature.
      DISCUSSION: The rubric tremor has been said to have its physiopathological origin
      in a lesion of the nigro-striate via and the efferent cerebellar vias at some
      point of the mesencephalic or subthalamic path, often without direct involvement
      of the red nucleus. CONCLUSIONS: The presentation of this type of tremor due to
      lesions which do not effect the red nucleus and the mesencephalum show the
      unsuitability of the name.

PMID- 9533214
TI  - [Prothrombotic states and cerebral ischemia].
AB  - INTRODUCTION: Hematological disorders per se represent unusual causes of cerebral
      ischemia, explaining in young people 4% of strokes. Hematological disorders that
      induce a thrombotic tendency contribute to overall ischemic stroke risk and may
      directly cause cerebral ischemia in patients without other risk factors. The
      frequency of cerebral infarctions caused by prothrombotic states is not known.
      DEVELOPMENT: This review will focus on disorders such as prothrombotic
      coagulopaties, including resistance to activated protein C and antiphospholipid
      syndrome as cause of cerebral infarction. Cerebral venous thrombosis and cerebral
      infarction from arterial origin are the most common form of neurological
      involvement. Pathophysiological mechanism of stroke in these patients are
      multiple and can include as in antiphospholipid syndrome embolism from valves
      abnormalities related to hematological disturbance, as well as thrombosis of
      extracranial or intracranial vessels. CONCLUSIONS: Is clear, however, that
      prothrombotic states could explains a high percentage of cases of those so called
      cryptogenic cerebral infarction in young people.

PMID- 9533215
TI  - [The molecular basis of neurodegenerative processes in the central nervous
      system].
AB  - INTRODUCTION: Investigations carried out in recent years indicate that there are
      three main mechanisms responsible for neurodegenerative processes affecting the
      central nervous system, particularly in advanced age. DEVELOPMENT: Of these three
      mechanisms, the first is based on the existence of errors associated with the
      pathways responsible for cell energy metabolism. Secondly, there is the formation
      of free radicals for different reasons. Finally, there is the hyperexcitability
      of amino-acid neurotransmitters, particularly glutamate acid. However, these
      three mechanisms which induce degeneration and neurone death seem to share a
      common factor: The increase in free calcium levels in the cytosol. CONCLUSIONS:
      Control of the maintenance of suitable levels of free Ca2+ in the cytosol, by
      means of drugs, may be of great help in preventing the intellectual deterioration
      which occurs in persons with different neurodegenerative disorders.

PMID- 9533216
TI  - [Praelections Valliosoletanae (1631) by Antonio Ponce de Santa Cruz, the first
      major Spanish treatise on epilepsy].

PMID- 9533217
TI  - [Vascular risk factors in patients with infratentorial vertebrobasilar ischemia].
AB  - INTRODUCTION: Arteriosclerosis is the commonest aetiology of vertebro-basilar
      ischemia (VBI). In the literature few studies mention the risk profile of
      cerebrovascular accidents at this site. MATERIAL AND METHODS: In order to
      establish whether this profile has specific characteristics, we carried out a
      transversal study of 70 patients with VBI of artherothrombotic origin situated in
      the brain stem or cerebellum, determining the prevalence of the main risk factors
      (RF). The results were compared with a control group of individuals who had no
      cerebral vascular pathology and also with another group who had arteriosclerotic
      obstructive lesions of the carotid artery as an example of involvement of another
      vascular territory. RESULTS: In the the group of patients with VBI we found
      greater prevalence of hypertension, smoking, ischaemic cardiopathy, peripheral
      vascular disease and excessive alcohol consumption together with raised levels of
      arterial hypertension, haematocrit, haemoglobin and total cholesterol as compared
      with the control group and within a similar range to the group of patients with
      ischemia of the carotid territory. We underline the high prevalence of diabetes
      in patients with VBI (45.7%), considerably greater than that of the control group
      (12.5%), than those with carotid pathology (20.4%) and that described in the
      literature (17-25%). CONCLUSIONS: According to our results, the prevalence of RF
      in VBI and in carotid pathology is similar, except in the case of diabetes. This
      may play a more decisive role in territory such as the vertebro-basilar, where
      vascularization is basically by small calibre vessels.

PMID- 9533218
TI  - [Vertebrobasilar ischemia of thrombotic and embolic origin].
AB  - OBJECTIVE: To analyze the mechanisms involved in the appearance of ischemia in
      vertebro-basilar territory, especially those of embolic or thrombotic
      characteristics. DEVELOPMENT: The mechanism of vertebro-basilar ischemia had not
      been adequately studied until a few years ago. This had led to the belief that
      most were due to a haemodynamic mechanism. However, in recent years studies of
      large numbers of patients, in whom cardiological and neurovascular evaluation had
      been systematically carried out, has shown that this is not so. In general, the
      commonest mechanism is embolism, both of arterial and of cardiac origin. Local
      thrombosis and a haemodynamic mechanism are less common. The arterial lesions
      most often associated with intra-arterial embolism have their origins in the
      intracranial segment of the vertebral artery. The most frequent sites of blockage
      by emboli are the distal segments of the basilar artery, the superior cerebellar
      artery, the posterior cerebral artery and the intracranial region of the
      vertebral artery-posteriorinferior cerebellar artery. CONCLUSIONS: The mechanism
      of vertebro-basilar ischemia is not homogeneous and can not be taken for granted
      in any patient in particular. For this reason it is necessary to carry out a full
      clinical study of patients with these symptoms, similar to that done for patients
      with carotid ischemia. This permits not only individualized, correct treatment of
      each patient but also a more complete knowledge of the mechanisms of ischemia in
      this territory.

PMID- 9533219
TI  - [Vertebrobasilar ischemia: diagnosis and prognosis].

PMID- 9533220
TI  - [Basilar artery rostral occlusion syndrome. Clinico-radiological assessment of 56
      patients].
AB  - We studied 56 patients, 30 women and 26 men ranging from 30 to 79 years of age
      (average age 64.5 +/- 10.4), who were admitted to our hospital between 1982 and
      August 1995 with clinical features compatible with occlusion at the level of the
      bifurcation of the basilar artery. The patients were selected following clinical
      and neuro-radiological criteria. All patients included in the study had two or
      more recent infarcts in the vertebro-basilar territory, related to involvement of
      the rostral region of the basilar artery. The diagnosis was confirmed by CT or MR
      scanning. The infarcts were in the thalamus, brain-stem, cerebellum and parieto
      occipital lobe. A thalamic infarct associated with an infarct in another region
      was the most frequent lesion. The CT-MR findings in the 56 cases were: 29
      patients presented with a unilateral thalamic infarct associated with another
      infarct (23 occipital, 8 parietal, 6 brain-stem and 2 cerebellum). There were
      eight patients with bilateral thalamic infarcts and seven with bilateral
      occipital infarcts. In six patients the occipital infarct was associated with
      another infarct at a different level (parietal or cerebellar) and six patients
      had cerebellar infarcts together with an infarct of the mid-brain. In 22 of the
      patients, lesions were found in three or more areas. The commonest clinical
      findings were: Motor deficit (69.6%), abnormal eye movements (44.5%), cerebellar
      dysfunction (42.8%), altered level of consciousness (32.1%), visual field defects
      (28.5%), pupil anomalies (19.6%). The most frequently associated risk factors
      were: Arterial hypertension (58.9%), a history of ACV (32.1%) and atrial
      fibrillation (21.4%). Mortality was 5.7%. In contrast to the classical
      descriptions, motor defecit was the commonest symptom in our series.

PMID- 9533221
TI  - [Vertebrobasilar dolichoectasia].
AB  - OBJECTIVE: Vertebro-basilar dolichoectasia is an anomaly which has been well
      known since the earliest days of clinical neurology. In spite of this neither the
      mechanism by which it is produced not its clinical importance are fully defined.
      In this paper we review basic clinical aspects of this pathology. DEVELOPMENT: In
      most cases the subjacent arteriopathy is arteriosclerotic. The clinical features
      are very varied and it may be asymptomatic. Sometimes the clinical findings are
      due to compression of adjacent structures, basically the cranial nerves.
      Trigeminal neuralgia and hemifacial spasm are the commonest findings. There is
      usually only one presenting symptom but several symptoms may occur at the same
      time. On other occasions the patients present with cognitive deficits; there is
      no obvious relationship of cause and effect between vertebro-basilar
      dolichoectasia and cognitive deterioration. Finally, there seems to be a
      predisposition to cerebrovascular accidents. Most cerebrovascular accidents
      associated with dolichoectasia are ischemic, although some are hemorrhagic.
      Nevertheless, from the point of view of prognosis, the importance of vertebro
      basilar dolichoectasia is not completely clear. At the present time, there are no
      therapeutic attitudes which are specific for this anomaly. CONCLUSIONS: Further
      studies of the practical results of detection of this anomaly and its natural
      history are necessary.

PMID- 9533222
TI  - [Vertebrobasilar artery dissection].

PMID- 9533223
TI  - [Basilar migraine and cerebral infarction].

PMID- 9533224
TI  - [Percutaneous transluminal angioplasty of the vertebrobasilar artery].

PMID- 9533225
TI  - [Isoniazid-induced toxic encephalopathy].

PMID- 9533226
TI  - [A sensation of obstruction in the nasal cavity due to trigeminal nucleus
      involvement].

PMID- 9533227
TI  - [Myalgia-fasciculation syndrome].

PMID- 9533228
TI  - [Human immunodeficiency virus infection in pregnant women in Africa].

PMID- 9533229
TI  - [Accidents among students in professional or technological schools in Lorraine].
AB  - BACKGROUND: School accidents in adolescents in professional and technological
      secondary schools are relatively frequent. This work investigates these accidents
      in Lorraine (a French region) to identify preventive measures. METHODS: A cross
      sectional study was carried out in 4,751 adolescents from five volunteering
      schools. Only accidents occurring during one school-year and declared to the
      Social Security Services as work accidents were studied. RESULTS: Incidence of
      accidents per 1,000 subjects was 52.0: 21.3 for accidents during sports and
      physical training (SPT), 7.8 for those occurring during school training (except
      SPT), and 22.9 for spare time accidents. The incidence increased strongly with
      age and differed greatly between the type of schools. Girls had more accidents
      during SPT than boys. Injuries during school training were wounds and contusions
      of upper limb while the injuries during SPT and spare time were mainly articular
      disorders, contusions, and wounds of the upper limb, the lower limb, and the head
      and neck. A physician was consulted in almost 100% of the injuries, a
      radiological examination was performed for 75%, and a surgical intervention for
      14% of the injuries. Absence from school, exemption from workshops and from SPT
      were frequent. The predominant risk factors were the type of activities,
      especially activities the adolescents were not accustomed to, personal behavior
      and risks taken by adolescents. CONCLUSION: Accidents are frequent, in particular
      among older adolescents. It is important to identify activities at risk, and to
      target prevention and awareness campaigns, assessment training to evaluate risks
      of each activity, and promoting safe behavior, although environmental factors
      cannot be excluded.

PMID- 9533231
TI  - [Quality assessment of the medical information on the standardized discharge
      summary].
AB  - BACKGROUND: DRG-based management of public hospitals in France involves the use
      of standardised discharge abstracts for the "Medicalisation of Information
      Systems Program". METHODS: To assess the quality of the medical information in
      these abstracts, a sample of 649 abstracts for 1994 was collected from the
      Hospices Civils de Lyon's data base. To validate the information in these
      abstracts, we reviewed the medical records of each patient. RESULTS: The results
      showed an error rate of 32% (CI: 28-36) for the diagnosis-related group and an
      error rate of 40% (CI: 36-44) for the principal diagnosis. There was no
      significant difference between these error rates and the calculation of "Indices
      Synthetiques d'Activite" (French system for attributing points to hospital stays
      according to DRGs categories). CONCLUSIONS: The quality of the medical
      information for the "Medicalisation of Information Systems Program" remains a
      major challenge not only for budget allocation, but also for the study of the
      case-mix in hospitals.

PMID- 9533230
TI  - [The HIV epidemic in Burkina Faso: current status and the knowledge level of the
      population about AIDS, 1994-1995].
AB  - BACKGROUND: It is important for HIV/AIDS control programmes to determine
      population knowledge on AIDS in order to develop appropriate Information,
      Education and Communication (IEC) messages. The objectives of our study were to
      determine the seroprevalence of HIV and syphilis among pregnant women, female
      prostitutes and long-distance truck drivers and to evaluate knowledge, attitudes,
      beliefs, and practice (KABP) with respect to the HIV/AIDS epidemic in these three
      groups in Burkina Faso. METHODS: We performed three cross-sectional serosurveys
      including face-to-face interviews on KABP between October 1994 and February 1995
      in three population groups. RESULTS: Overall, 1,294 pregnant women, 236 long
      distance truck drivers and 426 female prostitutes were recruited. HIV
      seroprevalence was 8% (95% Confidence Interval (CI): 6.6-9.6) among pregnant
      women, 18.6% (95% CI: 13.9-24.2) among long-distance truck drivers and 58.2% (95%
      CI: 53.4-62.9) in female prostitutes. The prevalence of syphilis was 2.5%, 9.3%
      and 15%, respectively. Most pregnant women (98%), long-distance truck drivers
      (96%) and female prostitutes (98%) had already heard of AIDS. However, the level
      of knowledge of HIV transmission routes, of risk factors for HIV transmission and
      of available preventive measures was very low. Consequently, 41% of pregnant
      women, 40% of long-distance truck drivers and an alarming 61% of female
      prostitutes reported that they did not feel themselves at risk for HIV. In each
      group, high levels of knowledge on AIDS were associated with increased awareness
      of AIDS risk and the adoption of preventive behaviours. Level of education was
      associated with knowledge of AIDS and condom use. However, in the 12 months
      preceding the surveys, condom use was very low among pregnant women (0.1%), long
      distance truck drivers (18%) and among female prostitutes (42%). CONCLUSIONS:
      These results indicate that HIV is widespread in Burkina Faso and that there is
      an urgent need to develop and evaluate HIV prevention strategies in the general
      population and among core groups such as female prostitutes and long-distance
      truck drivers. Interventions must include information campaigns, condom promotion
      and distribution, and sexually transmitted diseases control.

PMID- 9533232
TI  - [Risk reduction and intravenous drug use abstinence in patients with HIV
      infection. The SEROCO group].
AB  - BACKGROUND: Little is known about the complex stepwise process of giving up
      intravenous (i.v.) drugs. However, HIV risk reduction programs directed towards
      i.v. drug users have been accused by some opponents to encourage users to
      continue. In order to better assess the relationships between risk reduction and
      abstinence, we studied factors associated with abstinence in HIV-infected
      patients using i.v. drugs at enrollment in the SEROCO cohort (1988-1994).
      METHODS: 63 HIV-infected patients injecting i.v. drugs at enrollment were
      followed-up every 6 months with a clinical examination and a questionnaire
      concerning sexual and drugs practices since last consultation. Abstinence was
      defined as non injecting for at least 6 months. The 30 patients who became
      abstinent during a follow-up period of 3 years were compared to the 33 remaining.
      RESULTS: Abstinence during follow-up was not related to age at inclusion,
      duration of i.v. drug use, gender or marital status. However, patients who became
      abstinent were more likely to have a professional activity at inclusion than the
      remaining (70% vs 42%, p = 0.03). Before knowledge of HIV infection, frequency of
      injections, needle sharing and use of condoms did not differ between the 2
      groups. During follow-up, behavioural changes occurred in the two groups, but
      were more marked in those who lately became abstinent. These latter were more
      likely to always inject with new needles/syringes (57% vs 18%, p = 0.003), and to
      use condoms with HIV-negative partners or of unknown status (73% vs 39%, p =
      0.06). Professional activity and systematic use of new needles/syringes remained
      independently associated with abstinence in multivariate analysis. CONCLUSION: In
      this cohort, abstinence appeared as a stepwise process in which risk reduction
      preceded abstinence. This confirms that risk reduction programs do not work
      against those messages aimed at stopping i.v. drug use. Since this analysis
      selected particular subjects, enrolled in a cohort of HIV-infected patients,
      results should be confirmed in other samples of i.v. drugs users.

PMID- 9533233
TI  - Changes in serum cholesterol in employees after three years of multifactorial
      intervention.
AB  - BACKGROUND: To assess long-term effectiveness of a multifactorial intervention at
      the work-site on serum cholesterol levels. METHODS: Individualized face-to-face
      counseling was given to 1,555 employees (76.7% male; mean age = 42.3 years) by
      occupational physicians at four work-sites. After 3 years, a blinded assessment
      of the adequacy of the intervention was done. Implementation of the intended
      intervention by physicians was assessed as adequate in two work-sites (927
      employees) and inadequate in the other two (628 employees). Observed changes in
      serum cholesterol were analyzed in the followed-up individuals. Follow-up rates
      at each work-site were 78.6% and 44.5% for the adequate intervention, and 85.5%
      and 60.4% for the inadequate intervention. Changes in serum cholesterol were
      controlled for potential confounding factors (pre-test levels of risk factors,
      age, sex, body mass index, educational level, marital status, physical activity
      and alcohol consumption) by multiple linear regression procedures. RESULTS: When
      the intervention was adequately performed, serum cholesterol was significantly
      lowered with a mean reduction of 14.3 mg/dl (95% C.I.: 11.0 to 17.6) in those
      employees with baseline levels > or = 200 mg/dl. CONCLUSIONS: Adequacy of
      implementation of work-site programs determines their long-term effectiveness in
      reducing mean serum cholesterol levels.

PMID- 9533234
TI  - [A review of evaluation questionnaires for physical activity].
AB  - The need to evaluate or quantify an individual's physical activity often raises
      the problems of choosing the instrument which most adequately meets the
      requirements of the study. This article offers a presentation of various
      questionnaires available in the literature. It proposes a table intended to
      characterize these questionnaires as well as a summary of validation steps. These
      tools allow rapid comparisons between questionnaires and are helpful in guiding
      the user's choice of a well adapted questionnaire.

PMID- 9533235
TI  - [Prevention of viral hepatitis in travelers and expatriots in a tropical and
      subtropical environment].
AB  - Hepatitis A and B are hyperendemic in tropical and, to a lesser extent,
      subtropical countries. This high level of endemicity is in sharp contrast with
      the low frequency of these infections in the industrialized world. As a
      consequence, the incidences of hepatitis A and B are high among travellers to or
      foreigners living in tropical or subtropical countries. Therefore, these subjects
      should be vaccinated against hepatitis A and B. Furthermore, the usual preventive
      measures should be maintained. Risk of infection with the hepatitis C and E virus
      are much lower. Given the increasing number of travellers to tropical and
      subtropical countries, imported hepatitis is a public health problem for
      industrialized countries. Preventive measures must, then, be reinforced.

PMID- 9533237
TI  - [Central lipoma of the mandible. A new case].
AB  - Lipomas are benign neoplasms affecting many organs of the body with adipose
      tissue. As a bone central lesion they represent less than 1% of all lipomas. In
      the literature lipomas are reported in different bones: calcaneum, ribs, fibula,
      phalanges, ulna, frontal and parietal bone. In the jaws 8 cases have been
      reported, most of them representing radiographic findings the clinician
      diagnosing cyst or tumor, specially odontogenic tumor. No preference has been
      reported for any gender, age or race but the condition appears after the fourth
      decade. We report a case of central lipoma in the mandible with the clinical,
      radiological and histopathological findings and discuss its origin.

PMID- 9533236
TI  - [Vaccination status of French and European travelers: a study of 9,156 subjects
      departing from Paris to 12 tropical destinations].

PMID- 9533238
TI  - [Surgical treatment of pleomorphic adenoma of the parotid gland. Apropos of 192
      cases].
AB  - Tumors of the salivary glands are exceptional, representing approximately 2% of
      head and neck tumors. The parotid gland is most often involved, at a frequency
      reaching 80%. Histology examination generally shows a pleomorphous adenoma. The
      choice of a surgical technique best adapted to curative treatment depends on the
      type of tumor and is widely debated. Our management strategy is based on
      simultaneous histology examination and superficial parotidectomy. Several pre and
      intra-operative factors determine the need for resection. We verified our
      strategy with a retrospective study.

PMID- 9533239
TI  - [Post-traumatic adenoid cystic carcinoma of the lacrimal gland].
AB  - A young 17-year-old man was injured on the external orbital canthus and developed
      a tumefaction which remained stable. After 2 years the tumefaction with
      exophthalmia and visual troubles. Radiological investigations suggested two
      diagnosis: Organized hematoma or a lacrimal gland tumor. Surgical exploration
      found an apparently benign tumor but histologically it was a cystic adenoid
      carcinoma.

PMID- 9533240
TI  - [Intra-mandibular adenoid cystic carcinoma].
AB  - A case of mandibular cystic adenoid carcinoma was observed in a 49-year-old man.
      After slow progression, the diagnosis was directed to mandibular pseudocystic
      tumor. The treatment was enucleoresection. Histological findings in this
      exceptionnal lesion led to a discussion of the radioclinical diagnosis and
      etiopathogenic features of adenoide cystic carcinoma. The origin of this tumor is
      hypothesized to be heterotopic salivary inclusion although no histologicaly proof
      can be provided.

PMID- 9533241
TI  - [Ameloblastic fibro-odontoma. Clinical aspects and review of the literature].
AB  - Ameloblastic fibro-odontoma is a rare odontogenic tumor. It is formed by
      proliferation of epithelial odontogenic elements combined with ectomesechimal
      tissue. The presence of dentine, enamel and osteoid like tissue can be
      identified. Cases of sarcomatous degeneration have been described. In this work,
      we present two new cases of ameloblastic fibro-odontoma, analyzing the most
      important aspects of their differential diagnosis, with a review of literature.

PMID- 9533243
TI  - [Our experiences with the frontal flap. Apropos of 105 cases].
AB  - The plastic qualities and vascular reliability of the frontal flap have been
      widely used for reconstruction of facial tissue. We revised the files of 105
      patients who had undergone surgical repair of facial tissue loss with frontal
      flaps. The epidemiology, etiology of the repaired tissue loss and indications for
      frontal flap as well as the various techniques were analyzed: 66.7% of the
      patients were over 60 years of age; 74% had ambulatory surgical repair; 54.4% of
      the repaired tissue losses were situated in the nasal region; 80% of the losses
      were due to tumoral formations. The median flap was the most widely used (23.2%).

PMID- 9533242
TI  - [Surgical correction of the sagittal shift of the jaws in severe alveolar
      atrophy].
AB  - A method for treatment of sagittal discrepancy in edentulous patients is
      described, which includes simultaneous maxillary repositioning by means of a Le
      Fort I osteotomy and placement of endosseous implants. The technique of
      mandibular setback using the sagittal osteotomy of the mandible according to
      Obwegeser-Dal Pont's method and placement of implants in patients with extreme
      class III relationships is also presented. We outline the importance of thorough
      diagnosis, model surgery and its transfer at the time of the operation. The study
      of 12 consecutively treated patients with a follow up of 4.2 years showed
      functionally and esthetically good results after combined surgical and
      implantological treatment.

PMID- 9533245
TI  - [MALT lymphoma with parotid and gastric involvement during Gougerot-Sjogren
      syndrome].
AB  - Sjoren syndrome favors the development of lymphoma, particularly in the salivary
      glands with MALT lymphomas. The differential diagnosis with benign
      lymphoepithelial sialadenitis can be difficult. A 78-year-old woman had an oculo
      buccal sicca syndrome for 10 years and developed parotid hypertrophy. The first
      biopsy, performed 7 years before the present investigation had showed chronic
      lymphoepithelial sialadenitis. A second biopsy showed MALT lymphoma. Search for
      extension revealed a second gastric localization of the lymphoma. This patient
      had a particular immunophenotype, showing a CD5+ tumoral population frequently
      observed in mantel lymphomas and usually lacking in MALT lymphomas. Recently,
      however, another case similar to our own, has been reported in the literature.
      The observations raise the problem of distinguishing between mantel lymphoma and
      MALT lymphoma.

PMID- 9533244
TI  - [Isolated mandibular metastasis of cancer of the thyroid. Mandibulectomy and
      reconstruction using a free vascularized peroneal graft].
AB  - Isolated mandibular metastasis from a thyroid cancer is exceptional. In our
      observation, it was revealed 13 years after the thyroid cancer (papillo-vesicular
      carcinoma which was treated with total thyroidectomy, nodes resection and I 131).
      Treatment included interruptive mandibulectomy and reconstruction with a free
      composed vascularized fibular transplant. Follow-up was uneventful. Functional
      and morphological results were excellent. Isolated cases are reported in the
      literature. Surgical resection must be achieved. The originality of our
      observation is the mandibular reconstruction with a free vascularized fibular
      transplant.

PMID- 9533246
TI  - [Chronic lip ulcer. Apropos of a case of a superficial large diameter artery of
      the lower lip].
AB  - A case of chronic ulcer of the lower lip, which persisted for three years and
      resisted all locals treatments, is presented. Recovery was achieved with
      excision. The specimen was examined macroscopically, and showed a prominent
      inferior labial artery or calibre-persistent artery, an uncommon entity. Patient
      literature was reviewed.

PMID- 9533247
TI  - [Sickle cell anemia patients in oral medicine. What treatment? Apropos of a case
      and review of the literature].
AB  - We report a case of a cyst of maxillary in a patient suffering from sickle-cell
      anemia. A review of literature and therapeutic management is exposed.

PMID- 9533248
TI  - [Risks and complications anesthesia with intubation during dental treatment].
AB  - In many hospitals and dental clinics the delivery of dental care under general
      anesthesia is a routine practice. Most often mentally handicapped patients and
      uncooperative children are concerned. In order to minimise the risk of anesthesia
      related complications, an exact preoperative examination of anatomic
      particularities and accompanying diseases is mandatory. An analysis of 402
      anesthesias performed from 1992 to 1995 revealed a 13.9% of complications. Main
      problems observed were difficult intubation and marked drop in blood pressure.
      Despite of a relatively low anesthetic risk we still limit ambulatory anesthesias
      to patients belonging to the ASA risk groups 1 and 2 with a maximum extent of the
      narcosis of 2 hours.

PMID- 9533249
TI  - Medical education in the new millennium.

PMID- 9533250
TI  - Secondary prevention of stroke--new trials.

PMID- 9533251
TI  - Up to date review of the secondary preventive measures for recurrent ischaemic
      stroke and transient ischaemic episodes.

PMID- 9533252
TI  - Possible toxicity of herbal remedies.
AB  - Herbal remedies are rapidly gaining popularity throughout the world as a result
      of dissatisfaction with conventional medicines. It is a widely held belief that
      herbal preparations are "natural" and are therefore intrinsically harmless.
      However, their effects can be very powerful and potentially lethal if used
      incorrectly and their use as a substitute for conventional medicines may be
      ineffective. Toxic effects have been attributed to several factors including
      hepatotoxicity of main constituents, contamination of preparations by heavy
      metals or microorganisms, and adverse reactions due to age, and genetic and
      concomitant disease characteristics of the user.

PMID- 9533253
TI  - Second malignancies in cervical cancer patients in the west of Scotland.
AB  - A retrospective study was carried out to determine the incidence and nature of
      second primary malignancies in patients treated for cervical cancer in the West
      of Scotland. A total of 3911 patients treated for a primary cancer of cervix,
      diagnosed between 1975 and 1992, were identified from the West of Scotland Cancer
      Registry. The ratio of observed second primary cancers in the study cohort to the
      number expected to occur if incidence was the same as in the West of Scotland
      population as a whole was calculated. Of the 3911 women treated, 129 (3.3%) were
      diagnosed with a second primary malignancy. Tissues within the pelvic radiation
      field showed no significant excess of second primary tumours. A significant
      excess (O/E 2.52 [95% c.i. 1.89-3.30]) of second primary malignancy in the lung
      and pleura was identified even after correction for socio-economic deprivation.
      Women treated for cervical cancer in the West of Scotland appear to be at more
      risk of a subsequent cancer due to causes other than the late effects of
      radiotherapy.

PMID- 9533254
TI  - The value of cervical screening in women over 50 years of age--time for a
      multicentre audit.
AB  - This study reviews the cervical smear history of women developing CIN aged over
      50 years to consider if they might be discharged sooner from the cervical
      screening programme in Tayside Region. From the OCCURS database all women over 50
      years who developed CIN between 1 Jan 1993 and 30 June 1996 were identified and
      their smear history obtained. Results show that had women been discharged from
      the screening programme at age 50 following three consecutive negative smears and
      a negative exit smear then only two women with CIN 3 and one with microinvasive
      disease would have been missed in the subsequent three and a half years. A wider
      geographical survey of the incidence of CIN in this older age group is needed to
      determine whether it is cost beneficial and cost effective to continue cervical
      screening beyond the age of 50 years.

PMID- 9533255
TI  - Emergency sub total colectomy for chronic constipation.
AB  - Severe chronic constipation presents a significant management problem which may,
      occasionally, necessitate surgical intervention. Rarely emergency surgery is
      required and we report a case in which emergency subtotal colectomy was indicated
      to treat faecal peritonitis secondary to stercoral ulceration.

PMID- 9533256
TI  - Getting a validated guideline into local practice: implementation and audit of
      the SIGN guideline on the prevention of deep vein thrombosis in a district
      general hospital.
AB  - This paper describes the implementation of a specific clinical guideline on
      venous thromboprophylaxis and outlines the audit design and methods used to
      achieve this objective. A member of the clinical staff was seconded to oversee
      this implementation and co-ordinate audit of current in the main clinical
      specialties within the trust. The Trust Clinical Audit Committee agreed to fund
      this low cost initiative (approximately 3,800 pounds) from clinical guideline
      monies. Findings from the initial audit revealed a total of 224 patients
      identified as 'at risk' of developing deep vein thrombosis or pulmonary embolism.
      Of this number 72.8%, (n = 163), were prescribed prophylaxis compared with the
      pre-set standard of 90.0%. Fifty four percent, (n = 122), of all identified
      patients were prescribed the correct prophylaxis in accordance with SIGN
      guideline recommendations. As a result of the initial findings local prevention
      protocols were developed or upgraded as required in line with the national
      guideline. The repeat audit findings highlighted a significant increase in the
      number of 'at risk' patients prescribed prophylaxis rising from 72.8% to 97.4% (P
      < 0.001) and similarly from 54.5% to 95.9% for those prescribed the correct
      prophylaxis (P < 0.001).

PMID- 9533257
TI  - On being a medical student in the 1930s.
AB  - From a Minute Book which has survived the years, an account is given of matters
      discussed by the Clinical Medicine Board of the Royal Infirmary of Edinburgh in
      the 1930s. This Board consisted of the senior physicians in the hospital and the
      records give an indication of the excessively large number of students who were
      all having their clinical experience in the wards of the one hospital. In
      addition to the University students there were others studying for the Triple
      Qualification of the Royal Colleges. The pressure of this teaching on staff and
      patients was considerable. It was decided to transfer some of the tuition to
      Craigleith Hospital which became the Western General. In 1930 the male house
      doctors were awaiting their call-up. The administrator had to consider
      arrangements for the continuation of teaching if bombing took place. In March
      1941 the Polish Medical School was organised in Edinburgh.

PMID- 9533258
TI  - Components of variance: a miscellany.
AB  - Some general issues connected with components of variance are reviewed. These
      include matters of definition, of formal inference in a normal-theory context, of
      goodness of fit, and of simple methods for unbalanced data.

PMID- 9533259
TI  - Longitudinal models for AIDS marker data.
AB  - Over the past decade, researchers have put a great amount of effort into
      developing suitable models for the analysis of longitudinal CD4 data and other
      markers of AIDS progression. These models must be general enough to allow for
      different patterns of change in the marker data. In this paper, we review the
      existing literature including our preferred models which involve mixed effects,
      stochastic terms and independent measurement error. Adding stochastic terms to
      standard mixed effects models gives an interpretable and parsimonious method for
      generalizing the covariance structure of the measurement error and short-term
      variability. We focus on univariate and bivariate models with integrated Ornstein
      Uhlenbeck (IOU) stochastic terms. The IOU process allows for a range of
      biologically plausible derivative tracking that encompasses both random
      trajectory and Brownian motion behaviour. We illustrate these modelling
      techniques on longitudinal CD4 and viral RNA data.

PMID- 9533260
TI  - Increasing efficiency from censored survival data by using random effects to
      model longitudinal covariates.
AB  - When estimating a survival time distribution, the loss of information due to
      right censoring results in a loss of efficiency in the estimator. In many
      circumstances, however, repeated measurements on a longitudinal process which is
      associated with survival time are made throughout the observation time, and these
      measurements may be used to recover information lost to censoring. For example,
      patients in an AIDS clinical trial may be measured at regular intervals on CD4
      count and viral load. We describe a model for the joint distribution of a
      survival time and a repeated measures process. The joint distribution is
      specified by linking the survival time to subject-specific random effects
      characterizing the repeated measures, and is similar in form to the pattern
      mixture model for multivariate data with nonignorable nonresponse. We also
      describe an estimator of survival derived from this model. We apply the methods
      to a long-term AIDS clinical trial, and study properties of the survival
      estimator. Monte Carlo simulation is used to estimate gains in efficiency when
      the survival time is related to the location and scale of the random effects
      distribution. Under relatively light censoring (20%), the methods yield a modest
      gain in efficiency for estimating three-year survival in the AIDS clinical trial.
      Our simulation study, which mimics characteristics of the clinical trial,
      indicates that much larger gains in efficiency can be realized under heavier
      censoring or with studies designed for long term follow up on survival.

PMID- 9533261
TI  - Approximate hierarchical modelling of discrete data in epidemiology.
AB  - Hierarchical models are used in epidemiology to estimate and analyse multiple,
      related relative risks. Examples include meta-analyses of series of 2 x 2 tables
      and mapping of spatially correlated disease rates. Empirical transform and
      penalized quasilikelihood procedures, both of which may be implemented using
      standard programs for mixed model analysis, provide satisfactory approximate
      inferences for these problems when cell frequencies are large. Simulation studies
      show that, in certain situations involving small cell frequencies, penalized
      quasilikelihood provides satisfactory estimates of variance components and
      regression coefficients whereas the empirical transform approach does not.

PMID- 9533262
TI  - Statistical methods for population pharmacokinetic modelling.
AB  - A principal aim of population pharmacokinetic studies is to estimate the variance
      components associated with intra- and inter-individual variability in observed
      drug concentrations. The explanation of the inter-individual variability in terms
      of subject-specific covariates is also of great importance. Pharmacokinetic
      models are nonlinear in the parameters and estimation is not straightforward.
      Within this paper we review a number of estimation approaches which have been
      suggested for population pharmacokinetic analyses. We distinguish between
      Bayesian and non-Bayesian and fully-parametric, semi-parametric and nonparametric
      methods.

PMID- 9533263
TI  - Organization of the equine immunoglobulin constant heavy chain genes. I. c
      epsilon and c alpha genes.
AB  - We provide a restriction map of the equine c epsilon and c alpha genes as a
      molecular basis for isotype classification. Human and murine DNA probes were used
      for identification of homologous equine DNA sequences and for isolation of the
      equine c epsilon and c alpha genes from a genomic DNA library. A detailed map of
      the equine 5'-s epsilon/c epsilon-s alpha/c alpha-3' gene region was obtained.
      Equine c epsilon and c alpha DNA probes were prepared and used for restriction
      analysis of immunoglobulin heavy chain gene loci from different horses. This
      analysis indicated the presence of only one equine c epsilon and one c alpha gene
      in the haploid equine genome. In addition, for the equine c alpha gene, four
      haplotypes were identified according to BamHI restriction fragment length
      polymorphism (RFLP) of genomic DNA. The relative location of the c epsilon and c
      alpha genes 3' of the equine c mu and c gamma genes was determined by restriction
      analysis of equi-murine heterohybridomas.

PMID- 9533264
TI  - Isolation and characterisation of equine dendritic cells.
AB  - Despite their important role in initiating T-cell responses in other species,
      dendritic cells have not been studied in the horse. A method for isolating blood
      dendritic cells by adherence and metrizamide gradients was adapted to equine
      cells. A number of monoclonal antibodies (mAbs), including some which label
      dendritic cells in other species, were tested for immunochemical reactivity with
      the isolated blood dendritic cells, and sections of lymph node and spleen. 62 +/-
      6% of the isolated blood cells were MHC Class II positive and had typical
      dendritic cell morphology and only 4 +/- 2% contained non-specific esterase, a
      marker of mature macrophages. These dendritic cells also expressed MHC Class I,
      LFA-1, EqWC1 and EqWC2. Amongst the potentially cross-reactive antibodies a mAb
      against bovine CD1b was the most interesting by staining lymph node, but not
      blood, dendritic cells. Monoclonal antibodies against equine CD5 (T-cells),
      surface immunoglobulin (B-cells) and macrophages (CZ2.2) were used to enumerate
      the contaminating cells in preparations from blood by flow cytometry. 39 +/- 7%
      of the cells did not express T and B cell markers or CZ2.2 but were large and MHC
      Class II positive. Comparison of immuno-chemistry and flow data, together with
      examination of alveolar macrophages and adhered blood cells, all support the view
      that CZ2.2 detects a myeloid marker not seen on mature macrophages and possibly
      shared with dendritic cell precursors. The functional capacity of the isolates
      was assessed in terms of their stimulating ability in the mixed leukocyte
      reaction (MLR). Dendritic cell enriched isolates were more potent stimulators of
      MLRs than peripheral blood mononuclear cells or adherent cells. Thus equine
      dendritic cells isolated from blood express high levels of MHC Class I and II and
      LFA-1 and stimulate a vigorous MLR. They do not express markers characterising T
      and B cells but, by virtue of expression of the equine macrophage marker CZ2.2,
      appear closely related to mononuclear phagocytes.

PMID- 9533265
TI  - Auto IgG anti-IgE and IgG x IgE immune complex presence and effects on ELISA
      based quantitation of IgE in canine atopic dermatitis, demodectic acariasis and
      helminthiasis.
AB  - Atopic dermatitis is a common allergic disease manifestation in dogs; however,
      there is no correlation between clinical disease and detectable total serum IgE.
      Auto antibodies of the IgG subclass against IgE may affect the detection of serum
      IgE by immunoassay and may be important in the regulation of IgE production by B
      cells. ELISA were developed to detect serum antibodies specific for IgE using a
      newly available canine monoclonal IgE of known antigen specificity, generated
      from a canine x murine heterohybridoma. To test for correlation of auto IgG anti
      IgE levels with manifestation of atopic dermatitis, the sera from 101 atopic dogs
      were compared with sera from non-atopic dogs of various breeds, foxhounds
      manifesting clinical signs of demodectic acariasis and helminth parasitized
      random bred dogs for quantities of IgG anti-IgE measured in units/ml compared to
      a high titer standard serum. To test for serum effects on quantitation of IgE,
      known amounts of canine monoclonal IgE were added to various sera and measured by
      capture ELISA with detecting monoclonal antibodies specific for heat labile or
      heat stabile epitopes. Unheated sera from dogs manifesting clinical atopic
      dermatitis and helminth parasitized dogs had levels of IgG anti-IgE that were
      significantly lower than various breeds of dogs not manifesting dermatologic
      lesions and foxhounds manifesting demodectic acariasis. Heating sera at 56
      degrees C for 3 h to denature the high affinity binding site on the IgE heavy
      chain caused a marked increase over non-heated sera in detectable IgG anti-IgE in
      almost all dogs. This increase was most profound in helminth-infected dogs and
      foxhounds manifesting demodectic mange with 7 fold increases each, respectively,
      and in atopic dogs with a 5 fold increase compared to 3 fold increases for
      clinically-normal springer spaniels and all soft coated wheaten terriers. The
      terriers demonstrated an association of lower heated serum values of IgG anti-IgE
      with manifestation of a familial syndrome of protein-losing enteropathy and
      protein-losing nephropathy. The ability of mouse anti-canine IgE monoclonal
      antibodies specific for either heat labile or heat stabile epitopes to detect
      canine monoclonal IgE added to sera in known amounts varied from serum to serum
      and at different concentrations of the same serum, but did not correlate with IgG
      anti-IgE values for these sera. The range of absolute levels of serum IgE in dogs
      showing little or no inhibition of detection of added IgE was < 0.5
      ng/micromilligram to 2 micrograms/micromilligram. It was concluded that the
      increase in detectable IgG anti-IgE after heating sera indicates that IgG x IgE
      immune complexes are normally present in most dogs; however, the increase over
      uncomplexed IgG anti-IgE was most pronounced in dogs manifesting atopic
      dermatitis and demodectic acariasis. A quantitative comparison of IgG anti-IgE or
      IgG x IgE to total serum IgE was not made because the ability of monoclonal
      antibodies specific for either heat labile or heat stable epitopes on the IgE
      heavy chain to detect IgE added to serum, as well as innate serum IgE, was highly
      variable in different dilutions of serum from individual to individual.

PMID- 9533266
TI  - Increased surface expression of CD11b receptors on polymorphonuclear leukocytes
      is not sufficient to sustain phagocytosis during Escherichia coli mastitis in
      early postpartum dairy cows.
AB  - Phagocytosis, CD11a and CD11b adhesion receptor expression, O2-production and
      maturity of circulating polymorphonuclear leukocytes (PMN) were studied during
      acute coliform mastitis in early postpartum dairy cows to obtain a better insight
      in the role of neutrophils in the pathology of this disease. The mammary gland of
      twelve newly calved high-yielding dairy cows was experimentally infected with
      Escherichia coli. Variability in clinical signs of mastitis and inhibition of
      milk production among cows was very high. There was a significant negative
      correlation between the number of circulating neutrophils immediately before
      infection and severity of mastitis represented by the decrease in milk production
      of non-infected quarters two days after infection. Pre-infection phagocytosis of
      E. coli, CD11a and CD11b receptor expression, phorbol myristate acetate (PMA)
      induced O2-production and maturity of neutrophils on a per cell basis were not
      related to severity of mastitis. However, significant correlations between
      severity of mastitis and the total number of phagocytic PMN and mature PMN in
      blood immediately before infection were found. PMN characteristics responded
      differently to mastitis depending on the severity of the disease. Neutrophil
      functions from cows classified as severe (S) and moderate (M) responders to
      infection of the mammary gland were compared. Surface expression of CD11a
      receptors on PMN was decreased in all cows 24 h after infection, and this
      decrease was long-continued in S responders. A biphasic upregulation of the
      number of CD11b receptors on PMN was observed with a more pronounced response in
      S cows. PMN phagocytosis was decreased 12 h after infection in S cows and 18 h
      after infection in S and M cows and was normalized 24 h post-infection. The
      decrease of phagocytosis coincided with the first peak of CD11b receptor
      expression. Phorbol myristate acetate (PMA)-induced production of O2-by PMN was
      decreased for three days after infection in S responders compared to only one day
      in M responders and was followed by an upregulation. These data demonstrate a
      complexity in alterations of PMN functions during mastitis and suggest the
      involvement of differences in systemic factors dependent on severity of mastitis.

PMID- 9533267
TI  - Effects of growth hormone, insulin-like growth factor-I, and cortisol on
      periparturient antibody response profiles of dairy cattle.
AB  - The objectives of this study were to determine hormone and antibody response
      profiles from the prepartum period to peak lactation, and evaluate potential
      immunomodulatory effects of the classic endocrine hormones, growth hormone (GH),
      insulin-like growth factor-I (IGF-I) and cortisol. Specifically, 33 Holstein cows
      were immunized with ovalbumin (OVA) and Escherichia coli J5 at weeks -8 and -3
      prior to parturition. At parturition (week 0), cows received an additional
      immunization of OVA. Blood was collected at weeks -8, -3, 0, 3 and 6 relative to
      parturition and various samples were used to determine plasma hormone
      concentration, serum immunoglobulin (Ig), and specific antibody response to OVA
      and E. coli. Colostrum and milk samples were also collected post-parturition to
      monitor local immunoglobulin and antibody responses. Results indicated that not
      all periparturient cows exhibited depressed immune response, and that antibody
      response to OVA could be used to partition cows into 3 groups recognizing animals
      with sustained measurable antibody response before and after parturition (Group
      1), animals which responded poorly to immunization at parturition (Group 2), and
      animals which did not respond to immunizations at week -3 or parturition (Group
      3). Cows with the highest antibody response to OVA (Group 1) also tended (P < or
      = 0.10) to have the highest response to E. coli J5 at parturition and had the
      lowest incidence of disease, particularly mastitis. Antibody response to OVA
      measured in milk tended to be higher in Group 1 cows, particularly at week 0 (P <
      or = 0.06) compared to cows of Group 3. IGF-I was higher (P < or = 0.05) in cows
      of Group 1 than Group 3 at peak lactation (week 6).

PMID- 9533268
TI  - Purification and characterization of bovine dendritic cells from peripheral
      blood.
AB  - Optimal activation of T lymphocytes depends on TCR interaction with peptide/MHC
      complexes in conjunction with costimulatory signals, which are delivered by
      specialized cells called antigen-presenting-cells (APC). The population of APC is
      heterogeneous and includes dendritic cells, B cells and macrophages. The family
      of dendritic cells (DC) is widely distributed in tissues and plays a major role
      in the induction of primary T-dependent immune responses. The aim of this paper
      was to isolate and characterize dendritic cells from cattle. Two methods are
      described that have been used to isolate dendritic cells from bovine peripheral
      blood. One method involves sequential depletion of other cells, adherence and
      isolation of low buoyant density cells on Metrizamide column. The second involves
      enrichment of cells displaying receptors for plasma fibronectin, followed by
      adherence and separation on Metrizamide. Both preparations were characterized
      morphologically by flow cytometry and functionally. Both procedures produced
      enriched populations that did not express molecules typical of T cells (CD3, CD4,
      CD8, WC1), B cells (sIg, CD21) and monocytes (CD14, Fc gamma 2R). Procedure 2
      yielded cells with a typical veiled DC morphology that were highly effective at
      stimulating allogeneic T cells. Procedure 1 yielded cells that did not have the
      veiled morphology and were less effective in the MLR which may represent a more
      immature stage.

PMID- 9533269
TI  - The effect of dexamethasone on immunological memory to tetanus toxoid in sheep.
AB  - One of two groups of sheep was immunosuppressed with the glucocorticoid,
      dexamethasone, at the time of the first but not of the second of two booster
      vaccinations with tetanus toxoid given at an interval of 28 days. Treatment with
      dexamethasone decisively reduced the anti-tetanus antibody response to the first
      booster vaccination and affected both IgM and IgG1 antibody. However, antibody
      titres increased after the second booster vaccination in the treated sheep and
      were similar in size to those in the untreated sheep which rose in stepwise
      fashion after each booster vaccination. The differences in response imply that
      processes involved in displaying an anamnestic response and recalling previously
      established memory are sensitive to glucocorticoids. Accordingly, they can be
      separated from the glucocorticoid-resistant processes that lead to the expansion
      of immunological memory following multiple exposures to an antigen.

PMID- 9533270
TI  - The effects of recombinant ovine interleukin-3 and recombinant ovine stem cell
      factor on the growth and mediator expression of caprine and ovine bone marrow
      derived mast cells.
AB  - The growth of ovine and caprine mast cells in bone marrow cultures has been
      achieved using recombinant ovine interleukin-3 (rOvIL-3) and recombinant ovine
      stem cell factor (rOvSCF). After approximately 2-3 weeks' growth in optimal
      concentrations of either rOvIL-3 alone or a combination of rOvIL-3 and rOvSCF,
      the majority of the cells produced in bone marrow culture from both species were
      mast cells. The significant increase in the total numbers of cells and survival
      times of the cultures when both cytokines were present compared to either alone,
      indicated synergy between rOvIL-3 and rOvSCF on mast cell growth. Ovine and
      caprine cells cultured in rOvIL-3 alone produced a four-fold increase in cell
      numbers compared with medium only controls. The resulting cultures contained up
      to 52% mast cells by day 18 and had a lifespan of 3-4 weeks. In contrast, cells
      from both species grown in both rOvIL-3 and rOvSCF produced up to six times more
      cells than the equivalent rOvIL-3 stimulated cultures, contained up to 69% mast
      cells by day 21 and could be maintained for at least 6 weeks. Ovine cells grown
      in rOvIL-3 alone or rOvIL-3 and rOvSCF contained significantly more aryl
      sulfatase and serine protease but similar amounts of beta-hexosaminidase compared
      with caprine cells during the second week of culture. There were no significant
      differences in the granule-associated mediator content of cells from either
      individual species grown in rOvIL-3 alone compared with those grown in rOvIL-3
      and rOvSCF during the first 21 days of culture.

PMID- 9533271
TI  - Analysis of the immune response in sheep efferent lymph during Salmonella
      abortusovis infection.
AB  - The efferent lymph duct of the ovine prescapular lymph node was cannulated, and
      Salmonella abortusovis (SAO), a specific pathogen for sheep inducing abortion and
      mortality of newborn lambs, was inoculated by the subcutaneous route in this
      lymph node drained area. While the prescapular lymph node draining the
      inoculation site represented an efficient barrier for the vaccinal SAO Rv6 strain
      spreading, SAO 15/5 virulent bacteria were steadily detected in efferent lymph of
      infected sheep. The inoculation of the virulent strain of SAO induced a greater
      increase of the cell output than did the attenuated vaccinal strain, but
      proportions of blast cells appearing in the efferent lymph were similar in both
      cases. Flow cytometry analysis showed that B and T cell outputs were both
      increased during SAO infections, but while T cell subset proportions slightly
      decreased, B cell percentages significantly rose, and, at the peak response,
      almost all of the lymphoblast cells were activated B cells. Typical antibody
      profiles characteristic of a primary immune response were observed, and antibody
      titres were greater in the efferent lymph of animals inoculated with the virulent
      strain of SAO. Many of the cytokine mRNAs we investigated were steadily detected
      by RT-PCR in efferent lymph cells of control sheep, but frequencies of detection
      of IL-2, IFN gamma, IL-1 beta and TNF alpha mRNAs were augmented in efferent
      lymph cells following inoculation of both SAO virulent or vaccinal strains. IL-10
      and IL-8 mRNAs could only be detected after a SAO inoculation, while detection of
      IL-4 mRNAs was increased only in efferent lymph cells from SAO virulent strain
      infected sheep. The efferent lymph cannulation technique thus appeared a very
      powerful way to study the in vivo development of the immune response to SAO, in
      its natural host, the sheep.

PMID- 9533272
TI  - Antibody reactivity to the transmembrane protein of the caprine arthritis
      encephalitis virus correlates with severity of arthritis: no evidence for the
      involvement of epitope mimicry.
AB  - Serum and synovial antibody reactivities of caprine arthritis encephalitis virus
      (CAEV) infected goats were assessed by Western blotting against purified CAEV
      antigen and the greatest intensity of reactivity in the serum of arthritic goats
      was to the gp45 transmembrane protein (TM). The extracytoplasmic domain of the TM
      gene was cloned into a pGEX vector and expressed in Escherichia coli as a
      glutathione S transferase fusion protein (GST-TM). This clone was found to be
      90.5 and 89.2% homologous to published sequences of CAEV TM gene. Serum of 16
      goats naturally infected with CAEV were examined by Western blotting for
      reactivity to the fusion protein. Antibody reactivity to the GST-TM correlated
      with clinically detectable arthritis (R = 0.642, P < or = 0.007). The hypothesis
      that the immune response to the envelope proteins of the CAEV contributes to the
      severity of arthritis in goats naturally infected with CAEV via epitope mimicry
      was tested. Antibodies from 5 CAEV infected goats were affinity purified against
      the GST-TM fusion protein and tested for cross-reactivity with a series of goat
      synovial extracts and proteogylcans. No serum antibody response or cross
      reactivity of affinity purified antibodies could be detected. Peptides of the
      CAEV SU that were predicted to be linear epitopes and a similar heat shock
      protein 83 (HSP) peptide identified by database searching, were synthesized and
      tested for reactivity in CAEV goats using ELISA, in vitro lymphocyte
      proliferation and delayed type hypersensitivity (DTH) assays. Peripheral blood
      lymphocytes from 10 of 17 goats with long term natural CAEV infections
      proliferated in vitro in response to CAEV and in vivo 3 of 7 CAEV infected goats
      had a DTH reaction to CAEV antigen. However, none of the peptides elicited
      significant cell mediated immune responses from CAEV infected goats. No antibody
      reactivity to the SU peptides or HSP peptide was found. We observed that the
      antibody reactivity to the CAEV TM protein associated with severity of arthritis
      however epitope mimicry by the envelope proteins of CAEV is unlikely to be
      involved.

PMID- 9533273
TI  - Monoclonal antibodies defining differentiation antigens of swine lymphoid and
      myeloid cells.
AB  - Monoclonal antibodies recognising swine leucocyte antigens were identified and
      the corresponding antigens were characterised by determining their tissue
      distribution and molecular weight as well as immunohistochemical staining. On the
      basis of these data, we suggest that two antibodies are specific for a molecules
      within a porcine orthologue of one of the human CDII/CD18 complexes. We suggest
      that two others recognise swine wCD21, that one may recognise swine wCD6 and that
      another recognises an antigen designated by the International Swine CD Workshop
      cluster SWC9. Other antibodies were obtained which are specific for swine
      macrophages or B cells, but CD or cluster assignments for these antigens have not
      been made. Detailed analysis of the antibodies is presented. It is proposed that
      these antibodies will be useful in studies of the pig immune system and of virus
      infection.

PMID- 9533274
TI  - Production and characterization of monoclonal antibodies against mink leukocytes.
AB  - Three monoclonal antibodies (mAbs) were generated against mink leukocytes. One
      antibody reacted with all T lymphocytes, one with all monocytes and one had
      platelet reactivity. Under reducing conditions, the T lymphocyte reactive
      antibody immunoprecipitated 18 kDa, 23 kDa, 25 kDa and 32-40 kDa polypeptides and
      the platelet reactive antibody 17 kDa, 22 kDa plus two high molecular weight (>
      100 kDa) polypeptides. Immunohistological studies of the mAbs were performed in
      order to localize the cellular distribution of the detected antigens in various
      organs. The T lymphocyte reactive antibody detected an antigen, which was widely
      distributed in the T cell area of lymph nodes and spleen and in the thymic
      medulla. We conclude that this antibody is an anti-CD3 mAb and suggest that the
      platelet reactive antibody reacts to the CD41/CD61 integrin molecule. In addition
      to our own mAbs, more than 100 mAbs against leukocytes of human and various
      animal species have been analysed for cross-reactivity to mink leukocytes. We
      found eight to cross-react with mink. Of particular importance was an anticanine
      CD11a mAb, an antihuman CD79a mAb and an antihuman bcl-2 mAb.

PMID- 9533275
TI  - The effects of cyclosporin A and cyclophosphamide on the populations of B and T
      cells and virus in the Harderian gland of chickens vaccinated with the Hitchner
      B1 strain of Newcastle disease virus.
AB  - The cellular response to conjunctival vaccination with the Hitchner B1 strain of
      Newcastle disease virus was studied in the Harderian gland (HG) by
      immunohistochemistry. Bu-1+ cells and all subpopulations of T cells, (CD3+, CD4+,
      CD8+, TCR gamma delta, TCR alpha beta 1, and TCR alpha beta 2) were in the
      interstitial tissue between the ducts and the acini. Plasma cells with
      cytoplasmic IgM were more dispersed than the other cells and outlined the acini.
      Bu-1+ cells and all subpopulations of T cells increased at least three-fold after
      vaccination when compared to uninfected birds on the basis of the average cell
      counts in sections taken at 3, 5, 7, 10, 14, and 20 days after vaccination. The
      most marked increase was in the CD8+ cells which increased six-fold. Virus
      replicated for 10 days in cyclophosphamide (Cy) treated birds and for 7 days in
      cyclosporin A (CsA) treated birds compared with 5 days in untreated birds. Cy
      treatment prevented an antibody response to NDV and reduced Bu-1+ and IgM cells
      in the HG by 20-fold. Cy treatment resulted in a doubling of the number of T
      cells in the HG but these T cells may have been transiently disabled because it
      also caused a poor response of the lymphocytes in whole blood to the T cell
      mitogen concanavalin A (ConA). CsA reduced the T cell numbers in the HG and whole
      blood responses to ConA by about 4-fold but T cell numbers rebounded to normal
      resting values after vaccination with NDV. The clearance time was prolonged
      either by T cells being less numerous than normal after CsA or being disabled
      after Cy. T cells, but not B cells, may therefore be essential for virus
      clearance. CD8+ cells expanded more than CD4+ cells after the vaccination of
      untreated and CsA-treated birds indicating that CD8+ cells may be key players in
      vaccinal immunity to NDV.

PMID- 9533276
TI  - Induction of oral tolerance in carp (Cyprinus carpio L.) after feeding protein
      antigens.
AB  - Induction of oral tolerance against ferritin, recombinant surface glycoprotein of
      viral haemorrhagic septicemia virus (KLG18) and ovalbumin (OVA) was studied in
      carp. Feeding of ferritin or KLG18 resulted in lower Ab titres compared to
      unprimed controls when animals were intramuscularly (i.m.) injected with protein
      10 weeks later and sampled 21 days after this injection. After administration of
      OVA by different routes (oral, anal, i.m.) and i.m. injection with OVA + Freund's
      incomplete adjuvant 2 months later, only a few fish responded to OVA as measured
      by serum Ab titres. Responsiveness to OVA appeared to be carp strain dependent.
      When an isogenic carp strain was selected for an optimal response to i.m.
      injection with OVA, this carp strain did not develop oral tolerance after
      feeding. In contrast, 6 x feeding high doses of OVA on subsequent days, resulted
      in immunological memory formation. Oral tolerance can be induced in carp, but
      differences in tolerance induction may depend on the protein used. A possible
      role of genetic factors in the induction of oral tolerance in fish is discussed.

PMID- 9533278
TI  - Equine research: the HBLB highlights developments.

PMID- 9533277
TI  - Increase in gamma delta T cells in the ruminal mucosa of reindeer calves
      (Rangifer tarandus tarandus L.) induced by baled grass silage.
AB  - Leukocytes in the forestomach mucosa of reindeer (Rangifer tarandus tarandus L.)
      were investigated by immunoperoxidase staining of cryostat sections, using
      monoclonal antibodies against antigens on sheep leukocytes. Mucosal samples from
      three free-ranging reindeer calves were compared with samples from three calves
      fed baled grass silage previously shown to induce increased frequency of lesions
      in the ruminal epithelium. In both groups, MHC-II + cells and gamma delta T cells
      were observed, located within or just below the basal layer of the stratified
      epithelium. Computer-assisted morphometric analysis showed that the number of
      gamma delta T cells in the ruminal mucosa was higher in the silage-fed than in
      the free-ranging animals. No marked difference in number of MHC-II + Langerhans
      cells was observed between the groups.

PMID- 9533279
TI  - Epidemiological characteristics of bovine herpesvirus 1 infections determined by
      bulk milk testing of all Dutch dairy herds.
AB  - Samples of bulk milk were taken from all 33,636 Dutch dairy herds in November
      1994 and tested for the presence of bovine herpesvirus 1 (BHV-1) antibodies with
      a gB-blocking ELISA. Sixteen per cent of the herds had a negative BHV-1 status in
      the bulk milk. Farms with only dairy cows were 1.9 times more likely to have a
      negative or weakly positive BHV-1 status than herds which also had beef/veal
      animals. Farms in areas containing less than one herd/km2 were 1.5 times more
      likely to have a negative or weakly positive BHV-1 status than herds in areas
      with more than three herds/km2. Differences in numbers of animals per unit area
      were not significantly associated with BHV-1 status. The probability of herds
      having a negative or weakly positive BHV-1 status decreased linearly with herd
      size by a factor of 1.2 per 10 animals. The purchase of stock was significantly
      associated with a negative or weakly positive BHV-1 status, but there was an
      interaction between farm type and purchase of stock. For farms with both dairy
      and beef/veal animals there was a weak association between the purchase of stock
      and BHV-1 status. For pure dairy herds the probability of having a negative or
      weakly positive BHV-1 status decreased linearly with the numbers of purchased
      stock by a factor of 1.3 per 10 animals purchased.

PMID- 9533280
TI  - Ultrasonographic findings in five cows before and after treatment of reticular
      abscesses.
AB  - Five cows with reticular abscesses were examined clinically, haematologically,
      radiographically and ultrasonographically. They all had clinical signs typical of
      traumatic reticuloperitonitis, including chronic indigestion, pyrexia, an absence
      of or reduced ruminal motility, weight loss and a positive reaction to foreign
      body test. A haematological examination revealed anaemia, increased
      concentrations of plasma protein and fibrinogen and a decreased clotting time in
      the glutaraldehyde test. On the basis of the radiographic examination, a
      tentative diagnosis of reticular abscess was made in four of the cows, because
      the reticulum was displaced from the peritoneum or because there was an extensive
      gas-fluid interface in the reticular region. By ultrasonography, a large
      reticular abscess with a well developed capsule was visible in each of the cows.
      The abscess was located between the reticulum and ventral peritoneum in two of
      them, between the reticulumn and right thoracic wall in two and between the
      reticulum and spleen in the other cow. A foreign body penetrating the abscess
      could be visualised ultrasonographically in one cow. In two cows, the abscesses
      were drained through an ultrasound-guided transcutaneous incision. In the other
      three cows, the abscess was incised and drained from within the reticulum during
      a rumenotomy. Ultrasonographic examination revealed that the abscess had been
      completely evacuated in four cows, but only by about two-thirds in the remaining
      cow. All the cows were clinically healthy when they were discharged.

PMID- 9533281
TI  - Porcine nephropathy in Bulgaria: a progressive syndrome of complex or uncertain
      (mycotoxin) aetiology.
AB  - Macroscopic nephropathy was observed in 506 pigs at slaughter in Bulgaria in
      1993/94. Histopathological changes were mainly degenerative and proliferative,
      and were linked with kidney hypertrophy similar to that of the classical Danish
      Syndrome. Retention cysts formed by dilated tubules, activation or proliferation
      of capillary and vascular endothelium, and the development of neoplastic tissue
      were also observed. The most advanced pathology took the form of extensive
      interstitial fibrosis. Traces of ochratoxin A were found in the kidneys of the
      majority of 96 cases examined, and in some feed samples taken retrospectively
      from farms or commercial sources. The dietary ochratoxin concentration (100
      micrograms/kg), calculated from serum analyses, closely matched the average of
      individually analysed feeds. In other feeds no ochratoxin A was detected and the
      cosmopolitan mycobiota isolated did not include the ochratoxinogenic Penicillium
      verrucosum that caused the Danish syndrome. Aspergillus ochraceus was rare and
      the isolates did not synthesise ochratoxin in laboratory culture. The unconfirmed
      diagnosis of ochratoxicosis suggests a complex or multi-toxin aetiology for this
      rather common chronic disease in Bulgaria.

PMID- 9533282
TI  - Isolation of Mycobacterium kansasii from a tuberculin-positive goat.

PMID- 9533283
TI  - Arbovirus infections of ruminants in al-Rub al-Khali desert.

PMID- 9533284
TI  - Role of paraprofessionals in practice.

PMID- 9533285
TI  - Health risks from increased movement of companion animals.

PMID- 9533286
TI  - 'Stray voltage' and sudden collapse in horses.

PMID- 9533287
TI  - Early neutering of cats and dogs.

PMID- 9533288
TI  - Technology and diagnosis.

PMID- 9533289
TI  - Use of the bit in horses.

PMID- 9533290
TI  - Long-term prospects for horses with grass sickness (dysautonomia).
AB  - Responses to questionnaires were received from 31 owners of horses or ponies
      treated for chronic grass sickness (dysautonomia). Contrary to previous opinions
      the respondents indicated that the majority of the animals were capable of
      strenuous work, had regained the weight they had lost and, apart from a few
      residual problems such as difficulty in coping with dry fibrous food, had
      returned to a normal life. They had recovered slowly and had involved the owners
      in considerable extra work, but all the owners indicated that they considered the
      effort to have been worthwhile.

PMID- 9533291
TI  - Cluster analysis of the genetic heterogeneity and disease distributions in
      purebred dog populations.
AB  - Purebred dog populations have been subject to strong selection which has resulted
      in extreme differences between breeds and decreased heterogeneity within breeds.
      As a result, breed-specific inherited diseases have accumulated in many
      populations. The aim of this study was to analyse genetic heterogeneity in
      relation to the distribution of elbow dysplasia in labrador retrievers,
      portosystemic shunts in Irish wolfhounds, and hepatic copper toxicosis, in
      Bedlington terriers. Decreased heterogeneity was demonstrated in the multiple
      genetic interrelations in the three populations. In pedigrees containing seven
      generations of ancestors, the average number of common ancestors in all pair-wise
      combinations of dogs was five to six (range 0 to 18). These complex
      interrelationships were resolved by a cluster analysis on matrices of
      relatedness. This analysis gave clusters of highly related animals, the average
      relatedness of these clusters, and the average relatedness of the entire
      population, as expressions of its genetic variability. The mean relatedness was
      0.032 for Irish wolfhounds and Bedlington terriers, and 0.002 for labrador
      retrievers. The labrador retriever cohort was resolved into 31 clusters, and all
      cases of elbow dysplasia were concentrated in five highly related clusters with
      an overall incidence of 17 per cent. The Bedlington terrier cohort consisted of
      12 clusters which all contained cases of copper toxicosis, with an overall
      incidence of 46 per cent. The Irish wolfhounds were divided into 14 clusters with
      a disease incidence of 4 per cent. Dogs with portosystemic shunts were found in
      four averagely related clusters. A genetic distribution became obvious only when
      relatedness due to common ancestors of the cases was used as a criterion, and the
      cases were then concentrated in five highly related clusters.

PMID- 9533292
TI  - South American camelids in the United Kingdom: reproductive failure, pregnancy
      diagnosis and neonatal care.
AB  - The results of a postal questionnaire survey conducted between December 1992 and
      March 1993 indicated that a third of mated female South American camelids in the
      United Kingdom failed to produce offspring. This failure did not include
      abortions or stillbirths, which accounted for up to 4 per cent and up to 3 per
      cent of further reproductive losses respectively. The most common method of
      pregnancy diagnosis was observation (40 to 70 per cent). Plasma progesterone
      estimations and ultrasonography were used by a small proportion of respondents. A
      combination of methods was seldom used. Between 25 and 46 per cent of camelid
      owners housed their animals at parturition and 50 to 82 per cent routinely dipped
      the navel of the newborn calf. Neonatal mortality was an important cause of loss.

PMID- 9533294
TI  - ELISA detection of antibodies to glycoprotein E of bovine herpesvirus 1 in bulk
      milk samples.

PMID- 9533293
TI  - Induction of onion-induced haemolytic anaemia in dogs with sodium n
      propylthiosulphate.
AB  - The haemolytic effect of sodium n-propylthiosulphate, which had been isolated
      from boiled onions, was studied to determine whether it could be one of the
      agents responsible for induced haemolytic anaemia in dogs. The oral
      administration of 500 mumol/kg bodyweight of the compound to dogs resulted in a
      haemolytic anaemia associated with an increase of Heinz body formation in
      erythrocytes, which was more severe in dogs with the hereditary condition which
      results in erythrocytes with high concentrations of reduced glutathione and
      potassium than in normal dogs. In the affected dogs there was a 10-fold increase
      in the concentration of oxidised glutathione in their erythrocytes 12 hours after
      the administration of the compound, whereas in normal dogs there was almost no
      change.

PMID- 9533296
TI  - Apparent effect of management on the hour of parturition in mares.

PMID- 9533295
TI  - Isolation of Mycoplasma fermentans from a sheep.

PMID- 9533297
TI  - Aflatoxicosis as a possible predisposing factor for haemorrhagic enterotoxaemia
      in wild gazelles.

PMID- 9533298
TI  - Health risks from increased movement of companion animals in Europe.

PMID- 9533299
TI  - Role of paraprofessionals in practice.

PMID- 9533300
TI  - Recovery of cattle from malignant catarrhal fever.

PMID- 9533301
TI  - Tail-biting and tail-docking in pigs.

PMID- 9533302
TI  - BSE and hindsight.

PMID- 9533303
TI  - Early neutering of cats and dogs.

PMID- 9533304
TI  - Early neutering of cats and dogs.

PMID- 9533305
TI  - Treatment of anaemia in a piglet.

PMID- 9533306
TI  - Lead poisoning in swans.

PMID- 9533307
TI  - Endodontic-related inferior alveolar nerve and mental foramen paresthesia.
AB  - Paresthesia is a condition that involves perverted sensations of pain, touch, or
      temperature. It has a variety of possible causes. This article presents a
      literature review and case reports of endodontically related inferior alveolar
      nerve and mental foramen paresthesia. Nondrug prevention methods and the dental
      uses of dexamethasone are also discussed.

PMID- 9533308
TI  - Multifactorial aspects of legionellosis.

PMID- 9533309
TI  - A 21st century computerized injection system for local pain control.
AB  - This article describes a new computerized local anesthetic injection system for
      pain control. The core technology of this system is the microprocessor-controlled
      delivery of anesthetic solution at a constant pressure and controlled volume,
      regardless of encountered variations in tissue resistance. This fine-tuned, high
      suffusion flow rate of anesthetic provides a rapid onset of anesthesia for most
      patients. Traditional block injections and infiltrations as well as palatal
      injections and periodontal ligament injections are administered with precision,
      ease, and patient comfort.

PMID- 9533310
TI  - Effect of organic peroxide additives on wear resistance of composite resin.
AB  - The wear resistance of four proprietary posterior composite resins and amalgam
      were evaluated by an in vitro wear-testing system. Direct and indirect composite
      restorations were placed on occlusally flattened extracted molars. They were
      subjected to 400,000 cycles of artificial chewing. The vertical distance between
      the cavosurface margin and the worn occlusal surface, was measured to indicate
      the wear resistance of the restorative materials. The restorative systems,
      including a peroxide modifier, exhibited dramatic increases in wear resistance.
      The heat-treated composite inlay system exhibited minimal wear values compared to
      all other composite resins in the study. This system exhibited wear values that
      were less than those of the amalgam control group.

PMID- 9533311
TI  - Bone grafting materials for dental applications: a practical guide.
AB  - A variety of grafting materials are available for use in dental applications.
      Autogenous bone is the material of choice because of its osteogenic properties,
      which allow bone to form rapidly and under conditions where significant bone
      augmentation or repair is required. For other dental applications, allografts and
      alloplasts are appropriate. Knowing the physical and chemical properties of these
      materials and their mechanism of action, the correct graft or combination of
      grafts can be selected for each situation encountered. This article discusses
      current bone grafting options as reported in the literature since 1984. It
      emphasizes acquainting the reader with currently available materials and their
      properties.

PMID- 9533312
TI  - Advanced use of an esthetic indirect posterior resin system.
AB  - With the advent of newer indirect posterior restorative materials, one current
      resin restorative system still stands out as a proven leader in the dental
      marketplace. This article focuses on the multiple use of an all-microfill,
      laboratory-processed, indirect resin restorative system. Three cases are
      presented and criteria for long-term success are reviewed and discussed.

PMID- 9533313
TI  - A technique for placing multiple esthetic inlays and onlays.

PMID- 9533315
TI  - Complete dentures: are they out of phase with current therapy?
AB  - Complete dentures are truly a full-mouth reconstruction that functions in a
      dynamic environment and provides the completely edentulous patient with function,
      esthetics, phonetics, facial support, and self-esteem. Solutions to six of the
      most frustrating problems of complete denture treatment are described. These
      solutions provide enhanced treatment possibilities and mutual satisfaction to
      both the patient and the practitioner.

PMID- 9533314
TI  - Five cases of burning lips syndrome.
AB  - A recent retrospective study has suggested a new diagnostic entity called burning
      lips syndrome, which is distinct from burning mouth syndrome in that the burning
      sensation is generally limited to the lips, the labial mucosa is smooth and pale,
      the minor salivary glands of the lips are nonfunctional, and the syndrome
      presents with clinical symptoms. While burning mouth syndrome is more common in
      women, burning lips syndrome appears to affect men as often as it does women and
      typically occurs between 50 and 70 years of age. This article presents
      information on burning mouth syndrome as well as a prospective study of five
      cases used to evaluate the diagnosis of burning lips syndrome and its treatment
      with topical corticosteroids, which has been generally favorable.

PMID- 9533316
TI  - Necotizing gingivostomatitis: NUG to noma.
AB  - Necrotizing gingivostomatitis (NG) is an increasingly rare but potentially
      serious infection that can present as a spectrum of clinical disease ranging from
      necrotizing ulcerative gingivitis to noma. The diagnostic triad for NG is pain,
      interdental ulceration, and gingival bleeding, but many cases also display fetid
      breath and pseudomembrane formation. Etiology is believed to be an opportunistic
      bacterial infection occurring in individuals debilitated by malnutrition, human
      immunodeficiency virus infection, or other systemic factors, including inadequate
      sleep, unusual stress, recent illness, alcohol use, and smoking. Treatment for NG
      includes bacterial control by strict oral hygiene, antiseptic rinses, antibiotic
      use in selected cases, and correction of predisposing factors. In compliant
      patients, gingivectomy or gingival grafting may be indicated after initial
      healing to resolve any residual defects.

PMID- 9533317
TI  - Electronic thermography for the assessment of acute temporomandibular joint pain.
AB  - Electronic thermography (ET) has the potential to be a nonionizing, noninvasive,
      low-cost diagnostic alternative for evaluating temporomandibular joint (TMJ)
      disorders. This study was designed to evaluate the use of ET as a diagnostic aid
      in the assessment of patients with acute TMJ pain. Computer measurements made
      using facial thermography were able to distinguish normal patient populations
      from symptomatic patients with acute TMJ pain. Additional studies are needed
      before thermographic diagnosis of TMJ disorders will be clinically accepted.

PMID- 9533318
TI  - Survey of hepatitis B exposure and sharps injuries in dental health-care
      professionals.
AB  - Injuries associated with the category of dental surgical instruments known as
      "sharps" (i.e., syringe needles, glass, scalpel blades, dental burs, and hand
      instruments) are a serious concern for dental professionals because of the
      possible transmission of communicable diseases such as tuberculosis, hepatitis B
      virus, hepatitis C virus, and human immunodeficiency virus (HIV). Hepatitis B
      virus has been recognized as an occupational hazard for dentists and other health
      care professionals for several decades. The transmission of HIV from dentist to
      patient in the dental office has been known to occur in only one practice, and
      the vector of transmission remains unknown. No dentist has ever been reported to
      have contracted HIV from a patient. Adherence to infection-control procedures,
      especially barrier protection, has been linked closely to keeping the incidence
      of these infections low. This article discusses the results of an anonymous
      survey about "sharps" injuries and communicable diseases that was given to
      dentists/faculty, students, and support staff at an urban dental-school clinic.

PMID- 9533319
TI  - The epidemiology of AIDS/HIV infection: a review for the dentist.
AB  - This article reviews 14 recently published articles on the epidemiology of human
      immunodeficiency virus (HIV) infection. Each article is summarized and evaluated
      for its usefulness in helping the practicing dentist to perform the various roles
      of diagnosing and treating disease, managing auxiliary staff, providing community
      leadership, and educating fellow professionals and patients. Each article was
      selected based on timeliness, accuracy, and accessibility by a panel of two
      dental school faculty members, a physician and HIV information specialist, and a
      school of public health faculty member with extensive experience in HIV and
      acquired immune deficiency syndrome (AIDS).

PMID- 9533320
TI  - Single-appointment composite onlays.

PMID- 9533321
TI  - Clinical dentistry in the 21st century.
AB  - What will oral health care be like in the 21st century? During the 20th century,
      American dental education evolved from freestanding and often proprietary schools
      to become an integral part of research-intensive university professional
      education. This evolution provided a formidable scientific basis for diagnosis,
      therapeutics, disease prevention, and health promotion. The development of
      clinical skills coupled with advanced dental materials and therapeutics has truly
      been remarkable. And now we approach the 21st century as a nation of changing
      demographics. By 2010, nearly 40 million Americans will be 65 years old or older.
      Expectations for "quality of life" now punctuate American values. In 1900, the
      human life span was 45 years, but today it approaches 80 years. Although in 1900,
      the primary causes of mortality and morbidity were acute infectious diseases,
      today our challenges include complex viral-infectious as well as neoplastic and
      chronic disabling diseases (e.g., chronic facial pain, musculoskeletal
      degeneration, osteoporosis, osteoarthritis, and cerebrovascular and coronary
      diseases and disorders). In fact, one American dies every hour from oral cancer.
      Changes in the practice of clinical dentistry in the 21st century will: (1)
      integrate dental practice into comprehensive health care; (2) become increasingly
      proactive for health promotion; (3) represent an increased knowledge-base and
      computer-assisted technology approach for diagnostics and therapeutics; and (4)
      use novel strategies for oral health care ranging from gene-mediated therapeutics
      to community-based health promotion.

PMID- 9533322
TI  - Treatment paradigms in periodontal disease.
AB  - The prevailing treatment paradigm in periodontal disease relies on debriding the
      tooth surfaces to keep the bacterial load below the level that triggers tissue
      loss. When debridement cannot be easily accomplished because of deep pocketing,
      access surgery is recommended. The debridement approach that involves access
      surgery is successful in 80% to 85% of patients. Patients who do not respond are
      often treated with systemic antibiotics. This paradigm, which is based on the
      nonspecific plaque hypothesis, is labor-intensive and relies on antibiotics only
      as a last resort. This nonspecific treatment paradigm is in contrast with the
      specific plaque hypothesis, which states that a limited number of bacterial
      species are specifically involved in most forms of periodontal disease. Some
      studies have significantly associated anaerobic bacteria with advanced forms of
      periodontal disease. These observations led us to hypothesize that most forms of
      periodontal disease are anaerobic infections, which can be treated by
      antimicrobials such as metronidazole or clindamycin. Three double-blind studies
      have shown that 1 to 2 weeks of unsupervised use of metronidazole-plus
      debridement was significantly better than placebo-plus-debridement in reducing
      the need for periodontal surgery. These findings suggest that treatments based on
      the specific plaque hypothesis give clinicians and patients a choice regarding
      treatment options in periodontal disease.

PMID- 9533323
TI  - Prevention of pain.
AB  - Pain is a multistep process originating in the peripheral nervous system at the
      site of injury, transmitted by the peripheral nervous system, processed at
      several levels within the central nervous system, and finally perceived at the
      level of the cerebral cortex. Each of these steps in pain transmission is subject
      to intervention, with the possibility of reducing or blocking the nociceptive
      information to result in decreased pain. In general, therapeutic strategies that
      attempt to prevent the initiation or transmission of nociceptive information are
      more effective and safer than attempts to minimize pain after it occurs.
      Analgesic strategies based on knowledge of pain processes and results of
      controlled clinical trials should result in the prevention of pain in most
      patients, with fewer adverse effects than traditional analgesic therapy.

PMID- 9533324
TI  - Promising new dental materials on the horizon.
AB  - The rapidly evolving field of materials science is providing dentistry with new
      treatments and alternatives. Calcium phosphate materials are under development
      for bone repair and replacement, root surface desensitization, and for caries
      prevention, by greatly increasing the remineralizing efficiency of fluorides.
      Composites fabricated from calcium phosphates and polymers may have application
      as pulp capping and cavity-basing materials. An alternative to mercury dental
      amalgam is being investigated; it is composed of silver powders that are cold
      welded in the presence of a dilute acid. These materials are only a few of the
      technologies that may profoundly affect the future delivery of dental care.

PMID- 9533325
TI  - Improving outcomes using dental implants: integrating improvements in clinical
      practice.
AB  - Modern restorative dentistry is confronted with many challenges related to
      implant use in the craniofacial region, such as attempting to place implants in
      esthetically critical sites or anatomically limiting regions of the jaw. To
      assure a successful implant placement that is satisfactory to both the patient
      and the dentist, four key areas need to be improved: diagnostic procedures,
      surgical procedures and outcomes, esthetic results, and prosthetic complications.
      This article discusses how an integrated approach to these areas can improve
      clinical practice.

PMID- 9533327
TI  - Dramatic smile makeovers using direct resin veneers.

PMID- 9533326
TI  - Conservative management of a large odontogenic keratocyst.
AB  - Odontogenic keratocysts, although well recognized to have a high recurrence rate,
      are not invasive tumors and should not be treated by radical surgery with its
      attendant morbidity. A case report of successful management by fenestration for a
      time followed by successful enucleation suggests that conservative methods can be
      used in the treatment of large odontogenic keratocysts.

PMID- 9533328
TI  - Endodontic microsurgery and the surgical operating microscope.
AB  - Many clinicians have benefited from using surgical telescopes and headlamps to
      enhance the visual access of clinical procedures. Historically, the surgical
      operating microscope has provided opportunities for the medical community in the
      development of new treatment strategies. Recently, the operating microscope has
      been introduced into the endodontic community, and its benefits in surgical
      endodontics have become widely known. Cases that once seemed impossible can now
      be treated with a high degree of confidence and clinical success. This article
      describes the advantages of the surgical operating microscope.

PMID- 9533329
TI  - Histologic evaluation of the LaminOss osteocompressive dental screw: a pilot
      study.
AB  - This animal study compared the response of canine mandibular bone using the
      orthopedic principle of osteocompression by the function of an immediately loaded
      dental implant vs an unloaded dental implant of the same design and size. Two
      dogs were partially edentulated in the mandible. A total of 8 osteocompressive
      screw implants, 2 per quadrant were placed and evaluated histomorphometrically
      after 3 days in 1 dog and after 3 months in the second dog. The second dog had a
      two-unit fixed bridge placed immediately postsurgically in occlusal function on
      the right side; on the left side, the implants were splinted out of occlusion as
      a control. Histologically, no bone necrosis was observed at the implant interface
      by any of the 8 implants for either period as a direct result of the 4-mm
      diameter by 13-mm-length implant design. Clinical parameters did not differ among
      the implants; however, at 3 months, the immediately loaded implants demonstrated
      more than twice the amount of bone density at their surfaces compared to the
      unloaded implants of the same design. Future human clinical research would be
      necessary to provide a meaningful statistical analysis to validate the importance
      of this implant design and the function of osteocompression.

PMID- 9533330
TI  - Biomechanical advantages of wide-diameter implants.
AB  - In implant cases in which bone quantity and interdental space are sufficient,
      wide-diameter implants may be preferable to standard-size implants in restoring
      the partially edentulous patient. Although wide-diameter implants are often
      considered for their esthetic possibilities, they can also offer important
      biomechanical advantages, particularly in reducing the magnitude of stress
      delivered to various parts of the implant and in improving stability. In this
      article, standard 3.7-mm- and wide 4.7-mm-diameter implants are compared and
      discussed.

PMID- 9533331
TI  - Complete denture impressioning technique.
AB  - This article describes a technique that simplifies the making of an edentulous
      arch impression before the fabrication of a complete denture. Making an
      impression of an edentulous arch requires a unique combination of managing
      movable soft tissue commensurate with integrating different materials and a
      technique for accurate reproduction. The technique described requires a two-phase
      approach using a syringeable addition silicone during the border molding process
      and a condensation silicone wash material to capture the soft tissue while the
      functional border molding is repeated. These more recently developed products
      allow us to achieve similar results and are easier, faster, and more predictable
      than those products used previously.

PMID- 9533332
TI  - Building laminate veneers and fixed bridges with polymer glass technology.
AB  - A new type of material is being introduced to American dentistry. The material is
      a polymer glass, tested in Europe as Artglass. The material is purported to be
      equal to or better than porcelain for esthetic dentistry. The strength, color
      translucency, and color vitality allow minimal destruction of enamel for
      esthetics. An Artglass occlusal is less abrasive to enamel than porcelain and
      approximates gold. The characteristics of this material system introduces
      "minimal invasive dentistry" to routine dental repair and reconstruction. A case
      study of the senior author's reconstruction of his anterior teeth is presented.

PMID- 9533333
TI  - Atypical palatal papillomatosis treated by excision and full-thickness grafting.
AB  - Papillary lesions of the oral cavity are extremely common, and inflammatory
      palatal hyperplasia is well known to dental practitioners. Advanced
      sophistication in viral laboratory technologies makes it apparent that various
      forms of the human papilloma virus are often causative. However, this is not true
      for inflammatory palatal hyperplasia. This article describes a patient with
      anatomically well-demarcated, multiple squamous cell papillomas of the palate
      that could not be classified as inflammatory palatal hyperplasia, nor could a
      viral etiology be ascertained, despite exhaustive laboratory studies. The lesion
      recurred despite numerous surgical ablation attempts. Eradication was achieved
      only after applying free soft-tissue grafts over the areas of excision. The
      differential diagnosis of papillary lesions with an emphasis on viral etiology,
      laboratory studies associated with their identification, and a hypothesis that
      explains why grafting was the only successful means of treatment are also
      discussed.

PMID- 9533334
TI  - Postorthodontic restoration with a combination of gingivoplasty and porcelain
      veneers.

PMID- 9533335
TI  - The diagnosis and treatment of the gummy smile.
AB  - The diagnosis and treatment of the "gummy smile" (altered passive eruption,
      excessive gingival display) help the periodontist to provide the most beautiful
      smiles possible for patients. This article describes diagnosis, surgical
      planning, and case reports that show the benefits of treatment of this common
      clinical problem for the patient and restorative dentist who can now provide
      ideal cosmetic results for their patients.

PMID- 9533336
TI  - Guided tissue regeneration in the esthetic zone.
AB  - Common cosmetic failures in guided tissue regeneration (GTR) procedures performed
      in the esthetic zone include an unacceptable postoperative recession of the
      gingival flap and loss of the papillae. This article describes the dynamics of
      flap healing that contribute to esthetic failures. Specific technique
      modifications of GTR procedures that enhance the predictability of successful
      functional and esthetic outcomes are described.

PMID- 9533338
TI  - Forced eruption in the esthetic zone.
AB  - This article describes the background, technique, and benefits of forced eruption
      vs conventional osseous surgery in maintaining anterior esthetics. Four case
      reports will demonstrate the benefits of the procedure for maintaining esthetics
      and phonetics and preventing open interproximal spaces, which are seen frequently
      after conventional surgical procedures.

PMID- 9533337
TI  - Hard-tissue augmentation for the placement of anterior dental implants.
AB  - Dental implants have become a popular alternative for replacing missing teeth in
      every region of the oral cavity. In the anterior zone, special esthetic concerns
      require not only a stably anchored implant for long-term success, but also the
      presence of adequate hard and soft peri-implant tissues. Anterior tooth loss is
      often accompanied by considerable loss of alveolar bone, so augmenting hard
      tissue before or in combination with implant placement becomes a critical part of
      therapy. One of the most successful augmentation techniques is guided bone
      regeneration (GBR). Thus far, augmentation procedures using expanded
      polytetrafluoroethylene membranes (ePTFEa) have proved to be the most efficient
      and predictable surgical technique to enhance deficient bone sites. This article
      discusses some critical biological and clinical/technical aspects of GBR and
      describes techniques for anterior hard-tissue augmentation with the photographic
      documentations of three clinical cases.

PMID- 9533339
TI  - Esthetic crown lengthening for maxillary anterior teeth.
AB  - In the maxillary anterior region, the gingival labial margin position is an
      important parameter in the achievement of an ideal smile. The relationship
      between the periodontium and the restoration is critical if gingival health and
      esthetics are to be achieved. Periodontal therapy is a necessary and useful
      adjunct when any anterior restoration is undertaken. Anterior surgical crown
      lengthening may be undertaken to avoid restorative margin impingement on the
      biologic width. Crown lengthening is also used to alter the gingival labial
      profiles. This article discusses the esthetic parameters of ideal gingival labial
      positions and presents a classification of crown-lengthening procedures and the
      procedure for a two-stage crown-lengthening technique. The two-stage crown
      lengthening technique is surgically precise because healing is predictable.

PMID- 9533340
TI  - A new resin-reinforced glass ionomer cement for use with orthodontic attachments.
AB  - Resin cements are commonly used to bond orthodontic appliances. However, etching
      enamel and bracket bonding is an extremely technique-sensitive process. Moisture
      and saliva control, particularly in the gingival third of posterior teeth, is
      difficult and time-consuming, but is critical to success. Recently, a light-cure
      resin-reinforced glass ionomer cement was shown to perform with equal bonding
      capacity. This is accomplished in a wet field, without etching, and with the
      glass ionomer feature of fluoride release. Now, a self-cure resin-reinforced
      glass ionomer cement has been introduced. The self-cure cement will provide equal
      clinical success in areas where light curing is not possible or desired. This
      article compares traditional resin cements and glass ionomer cements for bonding
      orthodontic appliances.

PMID- 9533341
TI  - Treatment planning with modern materials.

PMID- 9533342
TI  - Pedicle procedure use in the management of regenerative therapy problems.
AB  - Regenerating a periodontium that has been lost because of disease has been made
      possible by the use of demineralized freeze-dried bone allografts (DFDBA), guided
      tissue regeneration with e-PTFE membranes, and combination therapies involving
      DFDBA covered by either an e-PTFE membrane or calcium sulfate. During
      regenerative therapy, problems may arise because of an adverse mucogingival
      condition, loss of a papilla, or significant exposure of the membrane from soft
      tissue recession, slough, or fenestration leading to direct exposure of the site
      to the oral environment. Pedicle procedures can be used to cover these
      regenerative sites while providing mucogingival repair.

PMID- 9533343
TI  - One-stage surgery with a nonsubmerged implant system.
AB  - Although nonsubmerged implant surgery can reduce patient trauma and costs by
      eliminating the uncovering procedure, one-piece implants cannot be shortened for
      esthetic results. However, a new implant design that comes preattached on a
      multipurpose collar is used for insertion, nonsubmerged healing, and as an
      abutment base. For submucosal margins, the collar can be replaced by an esthetic
      abutment that connects directly to the implant. Surface treatments include
      midsections roughened by hydroxyapatite or titanium plasma spray coatings, with
      smoother, acid-etched necks and self-tapping apical ends. Screw-retained,
      friction-fit abutments offer prosthodontic stability and uniformity, despite the
      submucosal implant type.

PMID- 9533344
TI  - Ceramic optimized polymer: the next generation of esthetic restorations--Part 1.
AB  - An abundance of new materials and techniques that challenge the clinician to
      recommend and provide the appropriate restoration for each clinical situation
      have been developed in the last decade. A new generation of materials, described
      by manufacturers as ceramic optimized polymers, have been recommended for a wide
      variety of restorations including inlays/onlays, crowns and bridges, and direct
      restorations. In this article, the appropriate preparation and luting technique
      for inlays/onlays are delineated. The use of ceromer inlays/onlays for teeth
      exhibiting symptoms of the partially fractured tooth is demonstrated.

PMID- 9533345
TI  - Amlexanox oral paste: a novel treatment that accelerates the healing of aphthous
      ulcers.
AB  - Five percent Amlexanox oral paste is a novel treatment for aphthous ulcers. In 3
      controlled clinical studies that evaluated 1,124 immunocompetent patients with
      mild to moderate aphthous ulcers, 5% Amlexanox oral paste (Aphthasol) was shown
      to accelerate healing of these ulcers. Treatment with Aphthasol reduced the
      median time to ulcer healing and to complete pain resolution in a statistically
      significant manner. This was true both when treatment with 5% Amlexanox oral
      paste was compared to treatment with a vehicle and when treatment with the
      Amlexanox paste was compared to no treatment. Study results after 3 days
      comparing treatment with the paste and no treatment indicated complete healing of
      ulcers for 21% and 8% of patients, respectively. Complete resolution of pain
      after 3 days was reported for 44% and 20% of patients, respectively.

PMID- 9533346
TI  - The full coverage restoration in relation to the gingival sulcus.
AB  - The full coverage restoration (FCR) and its effect on the periodontium have been
      the subject of much controversy over the last half century. The conflict relates
      to whether the margin of the FCR should be placed at or above the gingival crest,
      or into the gingival crevice. Clinicians and researchers alike have focused their
      attention primarily on the mechanistic aspects of fixed prosthetic design (i.e.,
      marginal configuration and fit). Although marginal quality and form are factors
      in the fabrication of the FCR, they alone will not determine periodontal health
      and restorative success. What determines the success of the FCR is its ability to
      restore form and function to the masticatory system without adversely affecting
      its biology. Each technical phase of treatment (i.e., tooth preparation,
      impression-taking, the provisional restoration, and the final restoration) must
      be performed within the limits of biologic adaptation. This literature review
      discusses the scientific evidence regarding FCR margin placement and periodontal
      health.

PMID- 9533347
TI  - Implant-supported overdentures: the ZAAG attachment system.
AB  - It has been amply demonstrated during the last decade that there are significant
      advantages to implant-supported overdentures beyond conventional complete
      dentures. Several attachment systems exist for connecting the overdenture to the
      implants, and practically all of them present notable benefits to the patients.
      This article discusses the use of the Zest Anchor Advanced Generation (ZAAG).
      This system, an outgrowth from the original Zest attachment, uses both individual
      implant attachments and bar attachments, and is compatible with all major implant
      systems. In addition to the retention, stability, and resiliency the ZAAG implant
      attachment system provides, it has the advantage of placing the resistance force
      of the attachment close to the implant body.

PMID- 9533348
TI  - Laboratory processed composite resin for posterior esthetic.

PMID- 9533349
TI  - Bone regeneration for reintegration in peri-implant destruction.
AB  - Complications and deterioration around functional osseointegrated implants stem
      from two major factors: bacterial-initiated disease and overloading. Peri-implant
      breakdown can occur during the postsurgical phase and before the reconstructive
      phase as a result of surgical trauma and/or predisposed compromised recipient
      bone site. Technical errors also potentially contribute to bone loss, which
      results in the loss of osseointegration. Two case reports associated with peri
      implant destruction are presented. The possible etiologic factors are discussed,
      and an attempt to regenerate lost peri-implant tissue is demonstrated via guided
      bone regeneration principles using barrier membranes.

PMID- 9533350
TI  - Endodontic surgical procedures.

PMID- 9533351
TI  - Impact of advances in diabetes care on dental treatment of the diabetic patient.
AB  - In medicine and dentistry, studies are published periodically that have a
      potentially wide-ranging impact on patient health and management. One such study
      is the Diabetes Control and Complications Trial (DCCT), which offers new hope for
      millions of individuals with diabetes and has begun to significantly alter
      medical management of these patients. Advances in the medical treatment of
      diabetes require a heightened awareness by dental practitioners of the various
      treatment regimens of their patients with diabetes, especially because of
      potential complications associated with diabetes care. Intensive medical
      treatment with oral agents and exogenous insulin injection promises to decrease
      the long-term risks of major complications of diabetes, but these treatments
      increase the risk of medical emergencies, especially hypoglycemia. This article
      reviews the findings of the DCCT, diabetes treatment regimens that might be
      encountered in a dental practice, and potential alterations to dental treatment
      protocols.

PMID- 9533352
TI  - Rotary reduction, enamel microabrasion, and dental bleaching for tooth color
      improvement.
AB  - Tooth color and shade can have an important influence on a person's appearance.
      Brown and white enamel dysmineralization defects, white hypocalcification
      lesions, and natural variations in tooth shading can detract from an otherwise
      attractive smile. Bonded facial composite resins, porcelain veneers, or full
      coverage restorations can be used for color correction. A more conservative and
      less expensive approach is to eliminate or reduce the discoloration. In select
      cases this can be done without removing significant tooth structure and without
      placing restorative material to mask the tooth. This article describes a
      combination of "microreduction," microabrasion, and dental bleaching for tooth
      color correction that has worked well for certain patients. The method is easily
      performed, conservative, inexpensive, and requires minimal subsequent
      maintenance.

PMID- 9533353
TI  - Anterior ridge preservation and augmentation using a synthetic osseous
      replacement graft.
AB  - A 7-year retrospective study, reporting 3 cases, is presented in which
      particulate synthetic osseous replacement grafts were placed for ridge
      preservation and augmentation in the maxillary anterior region after extraction
      of periodontally hopeless teeth. The ability of an osseous replacement graft to
      prevent and correct the postextraction atrophy of the alveolar ridge, as well as
      its esthetic implications in fixed prosthetics, is discussed.

PMID- 9533354
TI  - An epithelial exclusion technique using the CO2 laser for the treatment of
      periodontal defects.
AB  - When treating osseous defects associated with periodontitis, the healed result is
      a compromised regeneration of the attachment apparatus from epithelial
      downgrowth. This article demonstrates a laser ablation technique for excluding
      the epithelium from contacting the root surface of the periodontal wound. In
      accordance with the principles of guided tissue regeneration, the epithelium
      should be excluded for at least 30 days after surgical therapy. A series of case
      reports demonstrate the technique and the 6-month results that can be obtained
      using this approach. The regenerated tissue is confirmed through reentry
      procedures and radiographs.

PMID- 9533355
TI  - Clinical workstations: connecting technology with practice management.

PMID- 9533356
TI  - Psychogenic gagging: identification and treatment recommendations.
AB  - Uncontrollable disruptive gagging makes most dental procedures impossible to
      perform. Well-intentioned interventions by dentists often fail because of the
      inability to differentiate between psychogenic disruptive gagging and disruptive
      gagging of somatic origin. To help the clinician differentiate the diagnosis and
      management of somatogenic disruptive gagging from the psychogenic form, a review
      of the pertinent literature, diagnostic criteria, treatment recommendations, and
      a clinical case of psychogenic disruptive gagging are presented.

PMID- 9533357
TI  - The use of osteotomes for sinus augmentation at the time of implant placement.
AB  - The placement of endosseous dental implants is often hampered by the loss of
      alveolar bone. In the posterior maxilla, the presence of the maxillary sinus and
      less-dense bone present additional obstacles to successful implant placement.
      Existing methods of subantral augmentation require extensive surgical
      manipulation, often including a second surgical site for harvesting autogenous
      bone. The development of surgical osteotomes has facilitated the placement of
      implants in areas of minimal alveolar bone height in the posterior maxilla. This
      article describes the osteotome technique for sinus augmentation at the time of
      implant placement and presents a short-term evaluation of 34 implants placed in
      18 patients.

PMID- 9533358
TI  - Reconstruction of alveolar defects before implant placement.
AB  - Guided bone regeneration and bone grafting have been used to reconstruct
      defective alveolar ridges in preparation for implant placement. This phase of
      implant treatment is critical to a successful overall result. Remarkable advances
      that have occurred in techniques and materials enable us to place and restore
      implants in cases where previously it was not feasible. Three case reports are
      presented to illustrate successful management of different alveolar defects.

PMID- 9533359
TI  - Periodontal, implant, and prosthetic treatment for advanced periodontal disease.
AB  - This article reports a case that involved a challenge in multidisciplinary
      decision making. A patient presented with severe periodontal disease and the need
      for prosthetic rehabilitation for purposes of tooth replacement and the
      stabilization of periodontally compromised teeth. The initial diagnosis revealed
      that the treatment regimen would require periodontic, endodontic, and orthodontic
      treatment, as well as dental implants. This case report demonstrates teamwork and
      a sequential approach to a complex case in a postgraduate clinical setting.

PMID- 9533360
TI  - A multidisciplinary approach to restoring posterior bite collapse.
AB  - Treatment planning of posterior bite collapse cases with loss of vertical
      dimension can be complex. In cases where a patient's vertical dimension of
      occlusion has been lost, there often is drifting of posterior teeth, flaring of
      maxillary anterior teeth, and inadequate interarch space for a restoration. These
      factors are further complicated by the esthetic demands of the patient and the
      dentist and by the use of implants to replace missing teeth. This article
      presents a case report of a multidisciplinary treatment plan to achieve a
      functional and esthetic restoration.

PMID- 9533361
TI  - Complications in implant-supported overdentures.
AB  - Implant-supported overdentures have been advocated as an effective treatment
      option for edentulism. When compared with implant-retained fixed prostheses,
      clinicians may find them to be technically easier to provide. However, there are
      complications unique to overdentures that can be encountered before, during, and
      after the restoration phases. Managing these complications may require extra
      chair time and additional cost. This article discusses potential problems
      associated with the use of implant-supported overdentures and how to minimize
      these problems, and emphasizes the need for restorative informed consent.

PMID- 9533362
TI  - Bone grafting and osseointegrated implants in the treatment of cleidocranial
      dysplasia.
AB  - Cleidocranial dysplasia is a rare condition that presents a variety of problems
      for the restorative dentist. This article defines the basic characteristics,
      including the oral manifestations, of cleidocranial dysplasia and describes some
      of the available treatment modalities. It also presents a case in which iliac
      crest bone grafts and endosseous implants were used in the maxillary arch in an
      attempt to provide a retentive and esthetic overdenture for a young patient.
      Discussion of this case includes several questions concerning the rationale for
      using osseointegrated implants for a patient with this condition.

PMID- 9533363
TI  - Indirect composite resin restorations: esthetics and function without wear of
      opposing natural teeth.

PMID- 9533364
TI  - Lasers in periodontics: use and abuse.
AB  - Despite the suggestions that lasers are a desirable alternative to traditional
      periodontal root instrumentation and the recent FDA approval of the Nd:YAG laser
      for such application, numerous peer-reviewed articles concerning in vitro and in
      vivo results strongly suggest caution with respect to clinical application. There
      appears to be a high potential for laser-induced irreparable physical damage to
      the root surface. Further, residual char layers resulting from repeated laser
      exposure or improper choice of parameters may inhibit reattachment of soft
      tissues to the root surface. In addition, the use of lasers to remove calculus
      from subgingival pockets appears to be more efficient or predictable than
      traditional instrumentation and may, in fact, require root planing subsequent to
      the laser therapy to achieve the desired clinical goal.

PMID- 9533365
TI  - Microbiological diagnostics in periodontics.
AB  - Microbiological tests in periodontics can be of great help in determining the
      characteristics of a pathogenic infection, prescribing the optimal antibiotic
      regimen, and monitoring the effectiveness of treatment. However, they are not
      without potential pitfalls. Current microbiological tests vary considerably in
      sensitivity and specificity. A false-positive test result may lead to unnecessary
      therapy and patient distress. A false-negative test result may prompt the
      withholding of necessary therapy and the subsequent progression of disease. Also,
      diagnostic tests can be relatively expensive and uncomfortable for patients. This
      article attempts to determine the usefulness of various microbiological testing
      systems for the management of periodontitis patients.

PMID- 9533367
TI  - The importance of statistics as a tool for management and as a yardstick for
      valuations.
AB  - This article explains the importance of comparing statistics from year to year,
      especially when analyzing a practice for purchase, sale, partnership, or
      management. This is an invaluable tool that becomes a yardstick for measurement
      and should never be omitted or dispensed with.

PMID- 9533366
TI  - Genetic risk for severe periodontal disease.
AB  - The discovery of a genetic marker that is highly associated with increased risk
      for severe periodontitis is a major breakthrough in the clinical management of
      all dental patients. The marker is not diagnostic; rather, it is a prognostic
      test, and it is used to identify patients who are much more susceptible to
      plaque. Individuals who have the marker have a 6 to 19 times higher chance of
      getting severe periodontitis than those who do not have the marker. It is
      estimated that 30% of the US population will test positive. This new information
      supplements existing microbiology and immunology research. A limitation with the
      established view of the etiology of periodontal disease makes it difficult to
      explain to patients why they are more or less at risk based solely on their level
      of oral hygiene. It has also been difficult to predict the clinical outcomes of
      various treatments for individual patients because each person responds
      differently to their own plaque. The genetic discovery helps to explain why some
      people with a little plaque have a lot of disease, and why other people with a
      lot of plaque have only minor problems. By incorporating the constant factor,
      genetics, into your philosophy of practice, the patient's periodontal needs and
      desires can be better understood and managed.

PMID- 9533369
TI  - Searching for information on the World Wide Web--a guide for dental health
      professionals: Part 1.
AB  - Mastering the retrieval of valid information from the Internet can be
      challenging, especially for busy professionals with little time for learning the
      necessary techniques. This article provides a conceptual framework for browsing
      and searching for clinically relevant, valid information on the Web. Part 1
      provides an overview of the Web that includes information on access methods,
      general characteristics, and the main user interface (a browser). Concerns about
      information validity are also discussed. Part 2 will describe several common
      methods for searching the Web, including how to visit a web site directly, visit
      a directory site, and conduct a search via a search-engine site.

PMID- 9533368
TI  - Controversies in clinical endodontics: Part 3. Filling from the open position.
AB  - Controversies have been common in the clinical treatment of endodontically
      involved teeth for many years. This series of articles discusses the advantages
      and disadvantages of three of the major disagreements in the field at this time.
      They are: (1) What is the significance of lateral canals and how are they best
      filled? (2) Should treatment be completed in a single appointment or should
      multiple appointments be involved? And (3) Can the canal(s) be filled after the
      tooth is left open or should such treatment be avoided? This article discusses
      filling from the open position.

PMID- 9533370
TI  - A 7-year retrospective study of 423 immediate implants.
AB  - This article reports the results of a study conducted from 1989 to 1995 of 423
      hydroxyapatite-coated implants used for immediate tooth replacement after
      extraction in 353 patients with an age range from 15 to 68 years. The implants
      replaced teeth that were extracted because of periodontal disease, root
      fractures, and endodontic problems. Bone defects relative to the implant were
      treated with bone regeneration procedures using polytetrafluoroethylene (PTFE)
      membranes and resorbable collagen membranes with and without augmentation
      material (hydroxyapatite--188 cases, demineralized freeze-dried bone allograft-
      208 cases, and 27 cases without augmentation material). Histologic evaluation
      confirmed viability of the regenerated bone. The length of implants ranged from 8
      mm to 18 mm, and a total of 284 PTFE and 139 collagen membranes were used. During
      the 1-year follow-up, 1 implant was lost and an additional implant failed during
      the 7-year follow-up, with a final success rate of 99.53%.

PMID- 9533371
TI  - A randomized comparison of surfactant dosing via a dual-lumen endotracheal tube
      in respiratory distress syndrome. The Spanish Surfactant Collaborative Group.
AB  - AIM: To determine if 1-minute instillation of Curosurf via a dual-lumen
      endotracheal tube without interruption of mechanical ventilation could decrease
      the incidence of hypoxia (drop in oxygen saturation [SaO2] to <80%, or of
      transcutaneous partial pressure of oxygen [PtcO2] to <50 mm Hg [6.6 kPa]) and
      bradycardia (heart rate below 80 beats/minute) at dosing, without affecting the
      efficacy of the standard bolus delivery. DESIGN: Prospective, multicenter,
      randomized, nonblinded clinical trial. SETTING: Neonatal intensive care units of
      the Spanish Surfactant Collaborative Group. PATIENTS AND METHODS: One hundred
      ninety-eight infants (birth weight 600-2000 g) with respiratory distress syndrome
      needing mechanical ventilation with a fraction of inspired oxygen [FIO2] 0.40
      were randomized before 24 hours to receive 200 mg/kg of Curosurf, either by bolus
      instillation (n = 99) or by a simplified dosing technique (n = 99), giving the
      full dose in 1 minute via a dual-lumen endotracheal tube without positioning,
      interruption of mechanical ventilation, or bagging. Two additional doses (100
      mg/kg) were given within 12 and 24 hours of first dose, by the same method, if
      the infant still needed mechanical ventilation and had a FIO2 0.30. The effects
      of both procedures on the incidence of acute adverse events at dosing, gas
      exchange, ventilator requirements, and outcome at 28 days were compared. RESULTS:
      Fewer episodes of hypoxia (18 vs 40% of doses), and a smaller decrease in heart
      rate and SaO2 were observed in the dual-lumen group. Efficacy of surfactant,
      based on improvement of oxygenation, ventilator requirements, and number of doses
      required, was similar in both groups. Infants in the dual-lumen group had a lower
      total time exposure to supplemental oxygen (195+/-199 vs 266+/-221 hours). No
      differences in the incidence of air leaks, intraventricular hemorrhage, patent
      ductus arteriosus, bronchopulmonary dysplasia, or survival were observed.
      CONCLUSION: A simplified 1-minute Curosurf dosing procedure via a dual-lumen
      endotracheal tube without fractional doses, ventilator disconnection, changes in
      the infant's position, or manual bagging was found to reduce the number of dosing
      related adverse transient episodes of hypoxia. Although the simplified method
      appeared to be as effective as bolus delivery, this should be confirmed in a
      larger trial.

PMID- 9533372
TI  - Does increased QT dispersion in the acute phase of anterior myocardial infarction
      predict recovery of left ventricular wall motion?
AB  - QT dispersion has been recognized as an undesirable marker because of its
      association with arrhythmogenicity in patients with myocardial infarction, but
      the relation between QT interval dispersion and wall motion abnormalities has not
      been clarified. After the introduction of reperfusion therapy, it was recognized
      that T waves were inverted twice in the course of myocardial infarction. An
      investigation was made of the clinical significance of QT dispersion in relation
      to the presence of inverted T waves and left ventricular wall motion
      abnormalities in 34 patients (mean age, 59 years) with acute anterior myocardial
      infarction who underwent successful reperfusion therapy. The amplitude of the
      deepest inverted T waves occurring within the first 3 days (T1) and after 3 days
      (T2) of myocardial infarction were measured in electrocardiographic (ECG) lead
      V3. On the ECGs on which T1 and T2 were recorded, QT dispersion was calculated
      (QTd1, QTd2), and T1 and T2 were correlated with QTd1 (r = .65) and QTd2 (r =
      .47), respectively. The difference between the extent of asynergy in the acute
      phase and the chronic phase, which was evaluated by the centerline method, was
      correlated with T1 (r = .63) and QTd1 (r = .67). Patients with a QTd1 of 0.1
      second or longer showed a greater change in the extent of asynergy (23.4 +/-
      13.1% vs 4.9 +/- 9.8%, P < .01) and less asynergy in the chronic phase (19.9 +/-
      15.6% vs 46.5 +/- 14.0%, P < .01) than patients with a QTd1 of less than 0.1
      second. Thus, QT dispersion in the acute phase of anterior myocardial infarction
      indicates recovery of left ventricular wall motion. Prolongation of the local
      action potential duration of the myocardium that recovers from severe ischemia
      may be a contributor to the increased QT dispersion that results in inversion of
      T waves in the acute phase of myocardial infarction.

PMID- 9533373
TI  - Ischemia detection after myocardial infarction: diagnostic value of exercise
      induced QRS duration changes evaluated by a new computerized method.
AB  - A new computerized optical scanner was used to measure QRS complex duration
      during exercise stress testing, both pre- and postdischarge, as a means of
      ischemia detection after acute myocardial infarction. Thallium stress testing was
      used as a standard of comparison. Each patient underwent predischarge exercise
      testing (while receiving anti-ischemic drug therapy) and a postdischarge test 1
      month later (without anti-ischemic drug therapy), as well as thallium stress
      testing within 4 months of infarction. In the population of 68 patients, 42 of
      the predischarge tests and 43 of the postdischarge tests showed an ischemic
      response of QRS prolongation. When compared with thallium testing for QRS
      prolongation criteria, the sensitivity was 95% with a specificity of 77%
      predischarge and 89% with a specificity of 65% postdischarge. According to ST-T
      criteria, only 12 of 68 patients were positive for ischemia predischarge; this
      number increased to 29 postdischarge (predischarge sensitivity 24% and
      specificity 90%, with postdischarge sensitivity 68% and specificity 87%), when
      compared with thallium testing. Measuring QRS duration during exercise increased
      the sensitivity of detection of ischemic patients over that of ST-T criteria by
      71% predischarge and 21% postdischarge, with a 22-23% loss of specificity, and
      was apparently not influenced by anti-ischemic drug therapy.

PMID- 9533374
TI  - A standardized procedure for locating and documenting ECG chest electrode
      positions: consideration of the effect of breast tissue on ECG amplitudes in
      women.
AB  - Continuing uncertainty exists about standardized procedures for the placement of
      electrocardiographic (ECG) chest electrodes, technical variability being the
      largest error source for short-term variations in amplitudes and waveforms of the
      chest lead ECGs. To avoid presumed attenuation of ECG amplitudes by abundant
      breast tissue, anterolateral chest electrodes in women are often placed under the
      breasts and too low. There is also considerable uncertainty about locating the
      midclavicular line and the V4 electrode, particularly in obese persons and in
      women. We examined the effect of breast tissue protuberance on ECG amplitudes
      using ECG and anthropometric data on 6,814 women included in the Atherosclerosis
      Research in Communities Study (ARIC). The R wave amplitudes in anterolateral
      chest leads and the Sokolow-Lyon voltage decreased (P < .001 for all), and RaVL
      and the Cornell voltage increased significantly with increasing breast
      protuberance (P < .001 for all). However, these effects were small (15 microV or
      less for each 1-cm increment in breast protuberance), and R2 values were less
      than .01, indicating that breast protuberance alone explained less than 1% of ECG
      amplitude variations. When chest size and breast protuberance estimates were
      entered simultaneously into a multivariate regression model, chest size appeared
      to dominate, and model R2 values increased for positive associations with RaVL
      (R2 = .12) and the Cornell voltage (R2 = .04). Combined model R2 values remained
      < or =.01 for all other ECG amplitudes. A detailed step-by-step standardized
      electrode placement procedure was formulated. Because of the difficulties
      encountered in locating the left midclavicular line by visual inspection, we
      introduced well-defined procedures for identification and documentation of
      lateral chest electrode placement locations as a quality control method for
      clinical trials. Population data from the Third National Health and Nutrition
      Survey on the distributions by sex and race of chest electrode V4 and V6
      locations and anthropometric data on chest size and shape are presented in order
      to facilitate evaluation of the comparability of electrode placement procedures
      in various studies and for quality control in clinical trials. It is concluded
      that standardized procedures to document chest electrode placement locations are
      feasible. Breast tissue appears to have a practically negligible effect on ECG
      amplitudes, and in women, the placement of chest electrodes on the breast rather
      than under the breast is recommended in order to facilitate the precision of
      electrode placement at the correct horizontal level and at the correct lateral
      positions.

PMID- 9533376
TI  - Right atrial potential profiles during atrial fibrillation predict the success of
      atrial defibrillation.
AB  - The right atrial electric potential was measured in 29 patients with chronic
      atrial fibrillation, and the clinical utility of these measurements in predicting
      the success of atrial defibrillation was investigated. The endocardial electric
      potential was recorded at 12 sites within the right atrium (high, middle, and low
      loci of anterior, posterior, lateral, and medial sites of the right atrium) with
      an electrode catheter. The duration and polar displacement of the atrial waves
      were measured at the one site that showed the maximum atrial electric potential
      among the 12 sites. The ratio of the maximum to the minimum atrial electric
      potential (atrial wave ratio) was calculated. Patients were classified into two
      groups according to the success (n = 6) or failure (n = 23) of atrial
      defibrillation. Electrophysiologic data were compared between the two groups, and
      correlations were evaluated between the data and the maximal left atrial diameter
      obtained from M-mode echocardiography. The two groups did not differ in the
      duration and polar displacement of the atrial waves. However, the atrial wave
      ratio was significantly lower in the success group than in the failure group, and
      the success rate of atrial defibrillation was also significantly greater in the
      patients with an atrial wave ratio of 10 or lower. This ratio showed a positive
      correlation with the maximal left atrial diameter; it became more difficult to
      achieve atrial defibrillation as the atrial wave ratio increased. Thus, the right
      atrial electric potential profile of patients with atrial fibrillation is a
      useful predictor of the success of atrial defibrillation.

PMID- 9533375
TI  - Efficacy of low-energy T wave shocks for induction of ventricular fibrillation in
      patients with implantable cardioverter defibrillators.
AB  - The efficacy of low-energy T wave shocks for induction of ventricular
      fibrillation (VF) was evaluated in 33 patients undergoing implantable
      cardioverter defibrillator (ICD) implantation (33 sessions) or predischarge ICD
      testing (20 sessions). To induce VF, the ventricle was paced for eight cycles at
      a 400-ms cycle length (S1-S1), and the T wave was scanned with a monophasic shock
      (S2) delivered via the defibrillating lead system. Of 294 attempts, the T wave
      shocks induced VF in 65%, nonsustained ventricular tachycardia in 10%, and less
      than five ventricular beats in 25%. As compared with the failed T shocks, the
      mean energy of successful T wave shocks was higher and the S1-S2 coupling
      interval was shorter. When the S2 timing was examined in relation to the T wave
      peak, the VF induction efficacy was 37% for shocks delivered more than 70 ms
      before the T wave peak, 82% for shocks delivered 30-70 ms before the T wave peak,
      and 50% for shocks delivered less than 30 ms before or just after the T wave peak
      (P < .001). Thus, in patients undergoing ICD implantation or ICD conversion
      testing, the use of low-energy T wave shocks is an effective and safe method to
      provoke VF.

PMID- 9533377
TI  - ECG changes during furosemide-induced hypokalemia in the rat.
AB  - Electrolyte abnormalities have become an increasingly important cause of
      arrhythmias owing to the widespread use of high-potency diuretics. Hypokalemia is
      one of the common complications of diuretic use. Although some studies of
      hypokalemia induced by furosemide as well as of potassium-deficient diets in the
      rat have been reported, the electrocardiographic (ECG) changes during hypokalemia
      in the rat are poorly understood. This study was designed to examine such
      changes. For this purpose, hypokalemia was induced by furosemide administration,
      and the diagnostic criteria for ECG manifestations of hypokalemia were
      determined. During hypokalemia, conduction in most parts of the heart was
      suppressed to an extent depending on plasma potassium concentration. Prolongation
      of the QT interval was also observed, which agrees with findings in humans and
      dogs. Furthermore, prolonged durations of the P wave and QRS complex were
      observed during hypokalemia in the rat. The extent of alteration of the PR
      interval induced by hypokalemia was less significant than that of P wave and QRS
      complex durations. These results suggest that the excitabilities of the
      myocardium in the atria and ventricles may be affected by extracellular potassium
      level rather than by the atrioventricular conduction system in the rat. Wave
      amplitude, except that of the P wave, was decreased by severe hypokalemia. These
      changes were not dependent on the plasma potassium concentration. Typical T wave
      changes observed with hypokalemia in humans and dogs did not occur in the rat.
      The ECG manifestations of acute hypokalemia in the rat did not include the
      typical T wave changes seen in species with ST-segment type ECGs; however, other
      ECG parameter changes occurring with hypokalemia were qualitatively similar to
      those in other species. These results may be useful for testing the toxicity of
      potassium-depleting drugs in the rat.

PMID- 9533378
TI  - Electrophysiologic assessment of calcium channel blockers in transplanted hearts:
      an experimental study.
AB  - The effects of calcium channel blockers on automaticity, conduction, and
      refractoriness were studied in a model of heterotopic heart transplantation in
      dogs, which combined an innervated heart (recipient) and a denervated one
      (donor). Following the surgical procedure, 0.2 mg/kg verapamil (n = 10), 0.15
      mg/kg diltiazem (n = 10), or 5 microg/kg + 30 microg/kg/h nifedipine (n = 10) was
      administered intravenously. In basal situation and after drug administration,
      each heart was assessed for AV interval, cycle length, sinoatrial conduction
      time, atrioventricular node antegrade block point, and atrioventricular node and
      ventricular refractory periods; electrocardiographic PR and QT intervals and QRS
      complexes; systemic arterial, pulmonary artery, central venous, and pulmonary
      capillary wedge pressures; and cardiac output. The depressor effects of these
      calcium channel blockers on automaticity, refractoriness, and conduction were
      more intense in the transplanted hearts, very possibly because of the absence of
      adrenergic reflexes mediated by the autonomic nervous system; in particular,
      verapamil produced a great depression of sinus automaticity in a large number of
      cases.

PMID- 9533379
TI  - Atrial escape capture bigeminy.
AB  - Atrial escape capture bigeminy is a rare electrocardiographic entity. A case of
      atrial escape sinus capture presenting as true atrial bigeminy is reported.

PMID- 9533380
TI  - Supernormal conduction in a case of Mobitz type II atrioventricular block.
AB  - A 52-year-old woman exhibited Mobitz type II atrioventricular block with right
      bundle branch block and 1:1 atrioventricular conduction at or slower than 80
      beats/min. Electrophysiologic study revealed transient HV interval block followed
      by recovery from the block at shorter coupling intervals without prolongation of
      the H1H2 and H2V2 intervals, suggesting true supernormal conduction.
      Isoproterenol enhanced the supernormal conduction, with shortening of blocked
      intervals and recovery of atrioventricular conduction, while atropine caused
      their less marked enhancement. Linking (ie, retrograde concealment of the impulse
      to the distal His bundle region through the blocked right bundle branch) is
      considered a possible mechanism of supernormal conduction in this case.

PMID- 9533381
TI  - Post-ventricular tachycardia P wave change simulating atrial enlargement.
AB  - An abnormal P wave was observed in a child affected by prolonged idiopathic
      ventricular tachycardia (fascicular tachycardia). After sinus rhythm restoration,
      the P wave was very tall and peaked (0.5 mV in lead II), suggesting a diagnosis
      of atrial enlargement. No cardiac abnormality, however, was detected by clinical
      and echocardiographic examination. The P wave abnormality lasted for about 1
      month, with progressive voltage and shape normalization. These P wave changes
      were probably dependent on tachycardia; since the arrhythmia was long-lasting and
      characterized by atrioventricular dissociation, repetitive atrial contraction
      against closed atrioventricular valves caused stretching of atrial fibers,
      resulting in P wave abnormality. This observation suggests that very prolonged
      ventricular tachycardia may be associated with an electrocardiographic pattern of
      pseudoatrial enlargement.

PMID- 9533382
TI  - Is impaired memory for spatial location in Parkinson's disease domain specific or
      dependent on 'strategic' processes?
AB  - Spatial memory has been found to be impaired in Parkinson's disease (PD). To
      determine the nature of the deficit, we compared the performance of'standard'
      levodopa-treated patients with PD to that of matched control subjects in
      different situations: (i) spatial versus verbal conditional associative learning;
      (ii) 'global' versus 'local' contextual encoding; (iii) pattern span and related
      supraspan learning. The relationship between dopaminergic depletion, which
      characterizes the disease, and the impaired memory processes was investigated by
      comparing the performance of 'de novo' not yet treated PD patients to that of
      matched control subjects. Both groups of PD patients were impaired in all
      situations requiring strategic processes, shared a decreased pattern span and had
      a normal visuospatial learning once the pattern span was taken into account. All
      these results suggest that the memory deficit for spatial location observed in PD
      results mainly from a disturbance of strategic processes and from decreased
      attentional resources, which may be due, at least in part, to the dopaminergic
      depletion and related striatofrontal dysfunction.

PMID- 9533383
TI  - The left hemisphere and the selection of learned actions.
AB  - The left hemisphere's dominance for movement is well known. The basis of its
      dominance is less clear. We have tested 16 left hemisphere (LH) patients, 17
      right hemisphere (RH) patients and 12 neurologically normal controls on a battery
      of five tasks. The tasks were based on animal lesion and recording studies, and
      human imaging and magnetic stimulation studies that identified two distributed
      systems that are important for the selection of motor responses and object
      oriented responses. The LH patients were impaired on three response selection
      tasks: learning to select between joystick movement responses instructed by
      visual cues; learning to select between analogous object-oriented responses
      instructed by visual cues; learning to select movements in a sequence. Although
      we replicated the finding that LH damage impairs sequencing, some of the impaired
      tasks had no sequencing element. We therefore argue that the LH deficits are best
      explained as an impairment of response selection. This was confirmed by showing
      that LH subjects were unimpaired on a more demanding task-object discrimination
      learning-which imposed a greater memory load but had no response selection
      element. Moreover, the LH deficits could not be attributed to disorganization of
      movement kinematics. The lesions of the impaired LH group were widespread but
      always included the distributed systems known to be important for response
      selection-the dorsolateral frontal and parietal cortices, striatum, thalamus and
      white matter fascicles.

PMID- 9533384
TI  - Are the benefits of errorless learning dependent on implicit memory?
AB  - The effectiveness of errorless and errorful learning methods was compared in two
      experiments in which a group of memory-impaired individuals learned lists of
      single words. In both experiments, error prevention during learning resulted in
      higher levels of cued recall performance than trial-and-error learning.
      Experiment 1 showed that the beneficial effects of the errorless learning method
      extended over a delay of up to 48 hr and were also observed in free recall. The
      hypothesis that the benefits of errorless learning rely upon implicit memory was
      tested in Experiment 2. No evidence was found to support the hypothesis. Implicit
      memory was observed following both errorless and errorful learning, but there was
      no indication that enhanced performance in the errorless condition could be
      accounted for by implicit memory. There was no correlation between performance on
      a direct test (cued recall) and performance on an indirect test (fragment
      completion) for the same materials. Furthermore, the extent of priming was no
      greater for recalled items than non-recalled items in the cued recall test. It is
      proposed that the benefits of errorless learning in this paradigm stem from the
      effects of error prevention on residual explicit memory.

PMID- 9533385
TI  - Footedness is a better predictor than is handedness of emotional lateralization.
AB  - A tremendous amount of experimental work has attempted to identify reliable
      behavioural predictors of cerebral lateralization. Preferred handedness has been
      the most popular predictor, but some recent reports suggest that preferred
      footedness may serve as a more accurate predictor of functional laterality,
      especially in the left-handed population. The present study sought to test this
      claim by selectively recruiting individuals with either 'crossed' lateral
      preferences (right-handed and left-footed or left-handed and right-footed) or
      'uncrossed' lateral preferences (right-handed and right-footed or left-handed and
      left-footed). Lateralization of emotional perception was assessed with two blocks
      of the dichotic Emotional Words Test (EWT), and lateral preference for both
      handedness and footedness was assessed using self-report questionnaires. Ear
      advantage on the dichotic task varied significantly with preferred foot
      (P=0.003), but not with preferred hand. Cerebral lateralization may be more
      related to footedness than to other lateral preferences.

PMID- 9533386
TI  - Cortical plasticity in perceptual learning demonstrated by transcranial magnetic
      stimulation.
AB  - Performance on a wide range of perceptual tasks improves with practice. Most
      accounts of perceptual learning are concerned with changes in neuronal
      sensitivity or changes in the way a stimulus is represented. Another possibility
      is that different areas of the brain are involved in performing a task during and
      after learning it. Here, we demonstrate that the right parietal cortex is
      involved in novel but not learned visual conjunction search. We observed that
      single pulse transcranial magnetic stimulation (TMS) to the right parietal cortex
      impairs visual conjunction search when the stimuli are novel and require a serial
      search strategy, but not once the particular search task has been learned. The
      effect of TMS returns when a different, novel, serial search task is presented.

PMID- 9533387
TI  - Lateralization in chicks and hens: new evidence for control of response by the
      right eye system.
AB  - Domestic chicks show marked lateralization of visually evoked behaviour: left eye
      use is associated with, and has advantage for, the detection of novelty; right
      eye use is associated with the use of selected cues to determine what response
      should be given. Experiments undertaken to see how far such lateralization might
      be a transient feature of development showed similar patterns in both adults and
      chicks: (i) use of the right, but not the left, frontal field allowed the
      inhibition of pecks at a familiar social partner; (ii) in distant viewing, there
      was spontaneous preference for more use of the left eye when the social partner
      was familiar rather than unfamiliar. The chick data, in particular, support the
      hypothesis that the visual system fed by the right eye is especially competent in
      the control of response. This is shown by the ability of birds that are using the
      right eye to inhibit approach to an entirely novel potential social partner, and
      inhibit pecks at a familiar partner. The resemblances between chick and hen are
      sufficient to show that the basic adult pattern is already present in the young
      chick: the various developmental changes in features of lateralization, such as
      days of bias to control by one or other hemisphere, thus do not cause the
      appearance of the adult pattern.

PMID- 9533388
TI  - Face processing impairments after encephalitis: amygdala damage and recognition
      of fear.
AB  - Face processing and facial emotion recognition were investigated in five post
      encephalitic people of average or above-average intelligence. Four of these
      people (JC, YW, RB and SE) had extensive damage in the region of the amygdala. A
      fifth post-encephalitic person with predominantly hippocampal damage and relative
      sparing of the amygdala (RS) participated, allowing us to contrast the effects of
      temporal lobe damage including and excluding the amygdala region. The findings
      showed impaired recognition of fear following bilateral temporal lobe damage when
      this included the amygdala. For JC, this was part of a constellation of deficits
      on face processing tasks, with impaired recognition of several emotions. SE, YW
      and RB, however, showed relatively circumscribed deficits. Although they all had
      some problems in recognizing or naming famous faces, and had poor memory for
      faces on the Warrington Recognition Memory Test, none showed a significant
      impairment on the Benton Test of Facial Recognition, indicating relatively good
      perception of the face's physical structure. In a test of recognition of basic
      emotions (happiness, surprise, fear, sadness, disgust and anger), SE, YW and RB
      achieved normal levels of performance in comparison to our control group for all
      emotions except fear. Their results contrast with those of RS, with relative
      sparing of the amygdala region and unimpaired recognition of emotion, pointing
      clearly toward the importance of the amygdala in the recognition of fear.

PMID- 9533389
TI  - Language deficits in a child with omolateral (left) temporo-basal and cerebellar
      lesions.
AB  - We report the case of an 8-year-old boy with two distinct brain lesions, probably
      hamartomas or low grade gliomas: one in the left basal temporal region, with
      involvement of the fusiform gyrus, the other in the white matter of the left
      cerebellar hemisphere. Both lesions were diagnosed at seven, when NMR was
      performed because of partial complex seizure. A mild delay in the first language
      acquisition and a long-lasting difficulty in word retrieval were reported. On
      neuropsychological testing, language was impaired more in production tasks than
      in comprehension ones, with severe deficit in word finding. The etiological role
      of the two different lesions is discussed in relation to experimental evidence of
      the existence of a distinct language area in the basal temporal region (fusiform
      gyrus).

PMID- 9533390
TI  - Psychic trauma causing grossly reduced brain metabolism and cognitive
      deterioration.
AB  - While amnesia and other cognitive disturbances are usually caused by structural
      brain damage, there are a few instances in which environmental stress may induce
      neuronal death in memory-sensitive brain regions such as the hippocampus. Here we
      report on a patient who, after a single brief exposure to an event reminding him
      of a similar stressful event from his childhood, deteriorated immediately and
      persistently without manifesting structural, but manifesting functional, brain
      damage as measured by position emission tomography. This patient probably
      represents the first case in which a direct relation between a single psychic
      event and the occurrence of brain malfunctioning in cognition is documented by
      dynamic neuroimaging methods. Psychic shock may cause lasting reductions in brain
      metabolism with the consequence of severe intellectual malfunctioning.

PMID- 9533391
TI  - Reading of Japanese Kanji (morphograms) and Kana (syllabograms): a
      magnetoencephalographic study.
AB  - Magnetoencephalograms were recorded from six healthy Japanese subjects in order
      to investigate the areas in the cortices which are involved in the recognition of
      Japanese characters (Kanji and Kana). Forty-four Kanji (morphograms), 44 Kana
      (syllabograms) and 20 alphabet letters were used as stimuli. They were presented
      randomly and the subjects were required to read each stimulus and count the
      number of letters. The magnetic responses were recorded with dual 37-channel
      SQUID (Superconducting Quantum Interference Device) gradiometers from the
      temporal, parietal and occipital areas of the brain. The magnetic responses to
      Kanji and Kana were similar and consequently the locations of equivalent current
      dipoles (ECDs) to Kanji and those to Kana did not differ at any recording site.
      In all the subjects, ECDs were found in the posterior inferior temporal (PIT)
      areas approximately corresponding to Brodmann area 37 in the latency range of 150
      300 msec. These activities were found in both hemispheres without consistent
      laterality. The location of the ECD moved forward from posterior to anterior in
      the PIT area as the latency increased in all but one subject. Only one subject
      showed activities in the left angular gyrus. Since activities in PIT areas were
      also found in alphabet letters, the bilateral PIT areas are considered to play an
      essential role in reading.

PMID- 9533392
TI  - Recovery of function processes in human amnesia: evidence from transient global
      amnesia.
AB  - There are few clues as to the processes that underlie recovery of function from
      human amnesia. Evidence is offered from the perspective of a study of recovery of
      function during an episode of transient global amnesia (TGA) that occurred as a
      complication of a cerebral angiographic procedure being carried out in a
      neurosciences centre, and where there was therefore a unique opportunity to
      examine acute changes in memory function. This allowed us to conduct the first
      quantitative study where shrinkage of anterograde and retrograde memory loss was
      plotted at four separate intervals throughout the acute recovery process, and
      also 24 hr later. Recovery of retrograde amnesia preceded recovery from
      anterograde amnesia. Resolution of a naming deficit more closely paralleled
      recovery from retrograde amnesia rather than anterograde amnesia. Within
      retrograde amnesia for public events, there was a temporal gradient of memory
      loss, with more recent events affected to a greater degree than earlier events.
      Within anterograde amnesia, picture recognition memory preceded recovery of story
      recall memory. On the basis of these findings, and related observations in the
      published literature, it is proposed that recovery from some types of human
      amnesia, such as that associated with TGA, follows a 'lateral-to-medial' rule-
      lateral inferotemporal areas that play a major role in retrograde amnesia recover
      first from hypometabolism related to the TGA attack, followed by 'interface'
      areas such as the rhinal and parahippocampal cortices that are considered to have
      a role in both anterograde and retrograde memory functioning, with the last areas
      to recover physiological integrity being discrete limbic-diencephalic structures
      such as the hippocampus.

PMID- 9533393
TI  - Impairments of mental rotation in Parkinson's disease.
AB  - It is controversial whether parkinsonian patients are impaired on visuospatial
      tasks. In the present study, patients and normal control subjects judged whether
      pairs of wire-frame figures in different orientations were the same or different.
      The orientation difference between the figures was either in the picture plane
      (around the z-axis, or two-dimensional) or in depth (around the y-axis, or three
      dimensional). Reaction times and error rates were measured. For the two
      dimensional task, there were no significant differences in errors between the two
      groups, though Parkinsonian subjects were significantly slower to respond than
      the control group. In the three-dimensional task, patients had a different
      pattern of reaction times from the controls and made significantly more errors,
      which were systematic at large angular differences. The results suggest a
      visuospatial deficit in Parkinson's disease, which reflects problems in some
      aspect of the perception of extra-personal space.

PMID- 9533394
TI  - Are human anticipatory postural adjustments affected by a modification of the
      initial position of the center of gravity?
AB  - During a lateral leg raising task, the position of the center of gravity (CG) in
      the horizontal plane shifts towards the supporting leg prior to the movement
      onset. The aim of this study was to explore whether the anticipatory postural
      adjustments were calibrated as a function of the initial horizontal location of
      the CG. Experiments were performed on 8 healthy subjects, with three initial
      positions of the CG (close to the supporting leg, between the two legs, close to
      the moving leg). Simultaneous kinematic, kinetic and electromyographic (EMG) data
      were recorded with the ELITE. system. The results show that the duration of the
      kinetic variables and EMG pattern are scaled as a function of the distance
      covered by the CG and constitute the means of modulating the CG shift. They
      suggest that the evaluation of the support conditions is necessary to calibrate
      the CG shift, this is done during the early phase of the postural adjustments.

PMID- 9533395
TI  - Error-related scalp potentials elicited by hand and foot movements: evidence for
      an output-independent error-processing system in humans.
AB  - The error-related negativity (ERN) is a fronto-centrally distributed component of
      the event-related brain potential (ERP) that occurs when human subjects make
      errors in a variety of experimental tasks. In the present study, we recorded ERPs
      from 128 scalp electrodes while subjects performed a choice reaction time task
      using either their hands or feet. We applied the brain electric source analysis
      technique to compare ERNs elicited by hand and foot errors. The scalp
      distributions of these error potentials suggest that they share the same neural
      generator and, therefore, that the ERN process is output-independent. Together
      with other findings, the results are consistent with the hypothesis that the ERN
      is generated within the anterior cingulate cortex and is elicited by the
      activation of a generic error-processing system.

PMID- 9533396
TI  - Lesion-induced axon sprouting in the deafferented striatum of adult rat.
AB  - Synaptic replacement in rat striatum following a unilateral cortical lesion was
      investigated using electron microscopy and the anterograde tracer, biotinylated
      dextrin amine (BDA). In the deafferented striatum evidence of axon sprouting and
      synapse replacement was seen at 20 days after the lesion and most newly-formed
      axon terminals were labeled with BDA injected previously into the contralateral
      cortex. In addition, BDA-labeled fibers from the contralateral cortex formed
      multiple asymmetric axospinous synapses with deafferented striatal neurons, a
      morphological feature rarely seen in unlesioned rats. These data suggest that in
      response to a unilateral cortex lesion axons from the contralateral cortex sprout
      and reinnervated the deafferented striatal neurons and that reinnervation by
      'like' afferents maybe crucial for the establishment of functional recovery after
      the unilateral cortex lesion.

PMID- 9533397
TI  - Delayed rectifier potassium currents induced in activated rat microglia set the
      resting membrane potential.
AB  - The delayed rectifying outward K+ (IK) current was measured in lipopolysaccharide
      (LPS)-activated cultured rat microglial cells by using whole-cell patch clamp
      method. The current showed 'window current' where channels were available for
      activation but never fully inactivated. At near resting membrane potential some
      part of the current was able to be activated by depolarization. Among the several
      K+ channel blockers tested, only 4-aminopyridine (4-AP) was able to block most of
      the current and depolarize the membrane potential reversibly. These results
      suggest that 4-AP sensitive IK current plays a direct role of setting the resting
      membrane potential in LPS-activated microglia.

PMID- 9533398
TI  - Plasticity of tyrosine hydroxylase gene expression within BALB/C and C57Black/6
      mouse locus coeruleus.
AB  - The plasticity of tyrosine hydroxylase (TH) phenotype in the locus coeruleus (LC)
      of two pure inbred strains of mice, Balb/C (C) and C57Black/6 (B6), was
      investigated at the molecular level by radioactive in situ hybridization. The
      results demonstrated that in basal conditions, C mouse LC contains less TH-mRNA
      expressing cells than B6. After RU 24722-treatment, which induces long lasting TH
      gene expression in the LC, we previously reported an increase in TH-expressing
      cell number in C mouse LC only, equalizing TH phenotype between the two strains.
      Here, we demonstrate that strain specific plasticity of TH phenotype detected in
      spatially organized cells is associated with the regulation of TH-mRNA expression
      above a detectable level. These results suggest that interstrain differences and
      pharmacologically-induced phenotypic plasticity in TH phenotype may occur at the
      transcriptional level.

PMID- 9533399
TI  - Clustering of Pick bodies in patients with Pick's disease.
AB  - Clustering of Pick bodies (PB) was studied in the frontal and temporal lobe in 10
      cases of Pick's disease (PD). Pick bodies exhibited clustering in 47/50 (94%)
      brain areas analysed. In 20/50 (40%) brain areas, PB were present in a single
      large cluster > or =6400 microm in diameter, in 27/50 (54%) PB occurred in
      smaller clusters (200-3200 microm in diameter) which exhibited a regular
      periodicity relative to the tissue boundary, in 1/50 (2%) there was a regular
      distribution of individual PB and in 2/50 (4%), PB were randomly distributed.
      Mean cluster size of the PB was greater in the dentate gyrus compared with the
      inferior temporal gyrus and lateral occipitotemporal gyrus. Mean cluster size of
      PB in a brain region was positively correlated with the mean density of PB.
      Hence, PB exhibit essentially the same spatial patterns as senile plaques and
      neurofibrillary tangles in Alzheimer's disease (AD) and Lewy bodies in Dementia
      with Lewy bodies (DLB).

PMID- 9533400
TI  - Immunohistochemical analysis of developmental stage of external granular layer
      neurons which undergo apoptosis in postnatal rat cerebellum.
AB  - Some granule neurons naturally undergo apoptosis in the external granular layer
      (EGL) of the postnatally developing rat cerebellum. We analyzed the developmental
      stage-specificity of this apoptosis using double staining by in situ nick end
      labeling and immunohistochemistry against three proteins expressed at specific
      stages of granule neuron development. The amount of apoptosis of EGL neurons
      peaked on postnatal day 9. In the 9-day-old rat cerebellum, 54.0% of apoptotic
      EGL neurons expressed proliferating cell nuclear antigen. On the other hand, 22.2
      and 15.4% of apoptotic EGL neurons existed in the postmitotic and premigratory
      zone defined by expression of TAG-1 and 440 kDa ankyrinB, respectively. Thus,
      proliferative granule neurons undergo apoptosis more frequently than postmitotic
      granule neurons in EGL of the developing cerebellum. This suggests that there are
      developmental stage-specific mechanisms of apoptosis of cerebellar granule
      neurons.

PMID- 9533401
TI  - Circadian rhythm of brain-derived neurotrophic factor in the rat suprachiasmatic
      nucleus.
AB  - This study was conducted to determine whether the rat suprachiasmatic nucleus
      (SCN) is characterized by circadian expression of brain-derived neurotrophic
      factor (BDNF). In constant darkness, SCN content of both BDNF mRNA and protein
      oscillated in a circadian fashion. BDNF mRNA and protein levels in the SCN
      reached peak values during the early subjective day and during the subjective
      night, respectively. In contrast, the hippocampus showed no sign of circadian
      rhythmicity in its expression of BDNF mRNA and protein. Since BDNF enhances
      synaptic transmission in other brain regions, the coincidence between peak
      expression of BDNF protein in the SCN and the known interval of circadian
      pacemaker sensitivity to the phase-shifting effects of light may have some
      implications for the role of BDNF in the circadian regulation of the SCN
      pacemaker by photic signals from the retinohypothalamic tract.

PMID- 9533403
TI  - Direct projections from the periaqueductal gray to pontine micturition center
      neurons projecting to the lumbosacral cord segments: an electron microscopic
      study in the rat.
AB  - Direct projections from the periaqueductal gray (PAG) to the pontine micturition
      center neurons directly projecting to the lumbosacral cord segments were observed
      electron microscopically in the rat by a double labeling method. Biotinylated
      dextran amine (BDA) was injected into the PAG and horseradish peroxidase (HRP)
      was injected into the lumbosacral cord segments. After injection of BDA into the
      ventrolateral part of the PAG, many BDA-labeled axons were seen light
      microscopically in Barrington's nucleus; a moderate number of them were found in
      the pontine tegmental region just ventral to Barrington's nucleus (D-region
      [Ding, Y-Q., Takada, M., Tokuno, H. and Mizuno, N., J. Comp. Neurol., 357 (1996)
      318-330]). On the other hand, after injection of BDA into the dorsolateral part
      of the PAG, only a few BDA-labeled axons were seen in Barrington's nucleus or the
      D-region. BDA-labeled axon terminals were electron microscopically confirmed to
      be in synaptic contact with HRP-labeled dendrites and somata in Barrington's
      nucleus and the D-region. The results indicate that the ventrolateral part of the
      PAG is implicated in regulation of the micturition reflex.

PMID- 9533402
TI  - Adenovirus vector-mediated gene transfer into rat retinal neurons and Muller
      cells in vitro and in vivo.
AB  - The ability and efficiency of human type V adenovirus-originated vector with CAG
      promoter to transfer foreign genes was examined in the rat retina. We introduced
      the adenovirus vector, AxCALacZ with the reporter gene LacZ (beta-galactosidase
      gene) into cultured retinal cells, and then injected the vector suspension into
      the vitreous cavity of the eye. Beta-galactosidase staining was observed in both
      glial and neuronal cells in vitro and in Muller cells near the injection site in
      vivo. Adenovirus vectors with CAG promoter are useful and efficient for the
      expression of foreign genes in retinal cells.

PMID- 9533404
TI  - Tricresyl phosphate inhibits the formation of axon-like processes and disrupts
      neurofilaments in cultured mouse N2a and rat PC12 cells.
AB  - Tricresyl phosphate (1 microg/ml) inhibited the outgrowth of axon-like processes
      in mouse N2a neuroblastoma and rat PC12 pheochromocytoma cell lines induced to
      differentiate by serum withdrawal and nerve growth factor addition, respectively.
      By contrast, it had no effect on the outgrowth of processes by rat C6 glioma
      cells induced to differentiate with sodium butyrate. The effect on axon outgrowth
      in the two neuronal cell lines correlated with altered distribution of
      neurofilament proteins, as determined by indirect immunofluorescence with
      monoclonal antibody RMd09. Western blots of neuronal cell extracts probed with
      the same antibody revealed decreased cross-reactivity after exposure to tricresyl
      phosphate. The results suggest that tricresyl phosphate has a selective effect on
      neuronal cell differentiation, which involves impaired axon outgrowth, reduced
      levels of the neurofilament heavy chain and disruption of the neurofilament
      network.

PMID- 9533405
TI  - Toxic effects of beta-amyloid(25-35) on immortalised rat brain endothelial cell:
      protection by carnosine, homocarnosine and beta-alanine.
AB  - The effect of a truncated form of the neurotoxin beta-amyloid peptide (A beta25
      35) on rat brain vascular endothelial cells (RBE4 cells) was studied in cell
      culture. Toxic effects of the peptide were seen at 200 microg/ml A beta using a
      mitochondrial dehydrogenase activity (MTT) reduction assay, lactate dehydrogenase
      release and glucose consumption. Cell damage could be prevented completely at 200
      microg/ml A beta and partially at 300 microg/ml A beta, by the dipeptide
      carnosine. Carnosine is a naturally occurring dipeptide found at high levels in
      brain tissue and innervated muscle of mammals including humans. Agents which
      share properties similar to carnosine, such as beta-alanine, homocarnosine, the
      anti-glycating agent aminoguanidine, and the antioxidant superoxide dismutase
      (SOD), also partially rescued cells, although not as effectively as carnosine. We
      postulate that the mechanism of carnosine protection lies in its anti-glycating
      and antioxidant activities, both of which are implicated in neuronal and
      endothelial cell damage during Alzheimer's disease. Carnosine may therefore be a
      useful therapeutic agent.

PMID- 9533406
TI  - A human brain proteolytic activity capable of cleaving natural beta-amyloid
      precursor protein is affected by its substrate glycoconjugates.
AB  - Human brain proteins were partially purified by using arginine-Sepharose 4B
      affinity chromatography, which traps proteins having an affinity to certain
      groups of arginine residue, such as serine proteases and zymogens. Bound proteins
      were analyzed for binding and cleavage related to the brain beta-amyloid
      precursor protein (APP). They were then further separated and isolated using a
      preparative gel system having a liquid-phase collection apparatus, using a non
      denaturing gel system. Each fractionated protein was also analyzed for the above
      activity using natural APP. Among these, we found several fractions that bind
      preferentially to APP treated with chondroitinase ABC but not to intact APP, and
      that also generate particular beta-amyloid containing C-terminal peptides of APP
      via proteolysis. Our results suggest that sulfated glycoconjugates attached to
      APP play a role in the substrate specificity of APP for proteases, and also that
      the nature of natural APP processing mechanisms in vivo is very complex.

PMID- 9533407
TI  - Blockade of morphine- and amphetamine-induced conditioned place preference in the
      rat by riluzole.
AB  - Previous studies have shown that antagonists at glutamatergic N-methyl-D
      aspartate (NMDA) or alpha-amino-3-hydroxy-5-methyl-4-isoxazolpropionic acid
      (AMPA) receptors can disrupt the development or expression, respectively, of
      conditioned place preference (CPP) induced by drugs of abuse. The present study
      examined the effects of inhibition of presynaptic glutamate release by riluzole
      on the development of morphine- and amphetamine-induced CPP. Morphine (10 mg/kg),
      D,L-amphetamine (4 mg/kg) and riluzole (4 mg/kg) itself each produced a
      significant CPP; however, when riluzole was co-administered with morphine or
      amphetamine during the conditioning sessions, no CPP developed. It is concluded
      that non-specific disruption of glutamatergic neurotransmission prevents the
      development of morphine- and amphetamine-induced CPP.

PMID- 9533408
TI  - Apolipoprotein AIV codon 360 mutation increases with human aging and is not
      associated with Alzheimer's disease.
AB  - In order to evaluate genetic apolipoprotein polymorphisms as risk factors for
      Alzheimer's disease (AD), we studied apolipoprotein (apo) AIV after apoE, an
      apolipoprotein also present in the brain. The allelic distribution of apoAIV
      codon 360 polymorphism was no different in AD group (n = 120) compared with
      elderly healthy individuals (n = 119). Surprisingly, this polymorphism was over
      represented (11.40%, vs. 5.7% P < 0.005) in all these aged subjects (74.29 +/-
      8.46 years) and independently of the clinical and mental status compared with the
      younger population (39.00 +/- 9.69 years) of the same regional recruitment. These
      results suggest that the apoAIV (360:His) allele could be a marker of aging and
      longevity.

PMID- 9533410
TI  - Sodium-lithium countertransport: physiology and function.
AB  - Current opinions on the relationships between erythrocyte sodium-lithium
      countertransport kinetics and primary hypertension, hyperlipidaemia and diabetic
      nephropathy are reviewed. Problems associated with the assay are analysed. Some
      possible mechanisms that could modify the kinetics of ion exchange are examined.
      The question of what catalyses sodium-lithium countertransport is discussed, but
      not answered. Some models are put forward showing how a study of sodium-lithium
      countertransport kinetics could further our understanding of important disease
      processes.

PMID- 9533409
TI  - Heparan sulfate proteoglycans recognize ghost Pick bodies.
AB  - An anti-heparan sulfate proteoglycan (HSPG) monoclonal antibody (3G10) recognized
      irregular round structures (IRSs) of various sizes adjacent to tau-positive
      intracellular Pick bodies (PBs) in the granular cell layer of the dentate gyrus
      and the superficial layers of the parahippocampal and other temporal gyri in
      Pick's disease. Some intracellular PBs were also weakly immunostained with 3G10.
      Only part of the IRSs were double-immunostained with 3G10 and anti-tau antibody.
      Immunoelectron-microscopic examination revealed that IRSs were composed of
      aggregated fibrillary structures with a diameter of 10-20 nm, corresponding to
      the appearance of ghost PBs. These findings suggest that 3G10 identifies ghost
      PBs better than intracellular PBs, and that heparan sulfate proteoglycans are
      involved in the process of PBs extinction.

PMID- 9533411
TI  - Should exercise blood pressure be measured in clinical practice?

PMID- 9533412
TI  - Clustering of coronary risk factors with increasing blood pressure at rest and
      during exercise.
AB  - BACKGROUND: The metabolic cardiovascular syndrome is the label given to the
      clustering of unfavourable levels of a number of coronary risk factors in
      subjects with high resting blood pressures. We found recently that exercise blood
      pressure had a strong independent prognostic value. OBJECTIVE: To search for
      possible similar associations between exercise blood pressure levels and coronary
      risk factors by studying conventional and recently acknowledged coronary risk
      factors. METHODS: The study population comprised 1999 healthy men aged 40-59
      years. Age-adjusted coronary risk factor levels and their relation to resting and
      exercise blood pressures were studied. Resting blood pressure was measured after
      subjects had rested supine for 5 min. The exercise blood pressure used was the
      systolic blood pressure measured with the subject sitting on a bicycle ergometer
      at the end of a work load of 600 kpm/min (100 W) for 6 min. RESULTS: Besides
      corroborating the relation between the metabolic syndrome and resting blood
      pressure levels, we observed similar or even stronger associations between levels
      of various coronary risk factors and exercise blood pressure. We found rather
      strong, direct associations between exercise blood pressure and total cholesterol
      level, fasting triglyceride level and body mass index whereas inverse relations
      were found for glucose tolerance, physical fitness, pulmonary functioning and the
      ability to increase heart rate during exercise. Virtually all these associations
      had a level of statistical significance of P<0.001. CONCLUSIONS: High exercise
      blood pressure levels are strongly associated with unfavourable levels of a
      number of important coronary risk factors. A similar metabolic syndrome to that
      observed in subjects with high resting blood pressures therefore appears to be
      present in subjects with high exercise blood pressure responses. These
      associations may considerably amplify the independent risk of high blood pressure
      responses to moderate exercise.

PMID- 9533413
TI  - Limitations of the difference between clinic and daytime blood pressure as a
      surrogate measure of the 'white-coat' effect. Syst-Eur investigators.
AB  - BACKGROUND: The difference between clinic and ambulatory average daytime blood
      pressures is frequently taken as a surrogate measure of the 'white-coat effect'
      (i.e. the pressor reaction triggered in the patient by the physician's visit).
      OBJECTIVE: To assess the reproducibility of this difference and its relationship
      with clinic and average ambulatory daytime blood pressure levels. DESIGN AND
      METHODS: These issues were addressed with two large groups of subjects in whom
      both clinic and ambulatory blood pressures were measured, namely 783 outpatients
      with systolic and diastolic essential hypertension [Group 1, aged 50.8+/-9.4
      years (mean +/- SD)], participating in standardized Italian trials of
      antihypertensive drugs, and 506 elderly patients (group 2, age 71+/-7 years) with
      isolated systolic hypertension, participating in the European Syst-Eur trial.
      RESULTS: The clinic-daytime blood pressure difference for the essential systolic
      and diastolic hypertensive patients (group 1) was 13.6+/-14.3 mmHg for systolic
      and 9.1+/-8.6 mmHg for diastolic blood pressure (P always < 0.01). This
      difference for the elderly patients with isolated systolic hypertension (group 2)
      was 21.2+/-16.0 mmHg for systolic and only 1.3+/-10.2 mmHg for diastolic blood
      pressure (P < 0.01 and P < 0.05, respectively). In both studies little or no
      systematic clinic-daytime difference could be observed for heart rate. The
      reproducibility of the clinic-daytime blood pressure difference, tested for 108
      essential systolic and diastolic hypertensive patients from group 1 and 128
      isolated systolic hypertensives from group 2, was invariably lower than that both
      of daytime and of clinic blood pressure values. Finally, the clinic-daytime blood
      pressure difference was progressively higher for increasing levels of clinic
      blood pressure and progressively lower for higher levels of ambulatory daytime
      blood pressure. CONCLUSIONS: Thus, the clinic-daytime blood pressure difference
      has a limited reproducibility; depends not only on clinic but also on daytime
      average blood pressure, which means that its size is a function of the blood
      pressure criteria employed for selection of the patients in a trial; and is never
      associated with a systematic clinic-daytime difference in heart rate, which
      further questions its use as a reliable surrogate measure of the true pressor
      response induced in the patient by the doctor's visit.

PMID- 9533414
TI  - Nitric oxide synthase gene polymorphisms, blood pressure and aortic stiffness in
      normotensive and hypertensive subjects.
AB  - BACKGROUND: Genetic studies may help us to understand the mechanisms underlying
      the involvement of various neuro-humoral factors in the regulation of the
      mechanical properties of large arteries. We have shown previously that the
      angiotensin II type 1 receptor gene polymorphism was a strong determinant of
      aortic stiffness in hypertensives. OBJECTIVE: To assess the contribution of two
      polymorphisms of the endothelial nitric oxide synthase gene to aortic stiffness
      in normotensive and hypertensive subjects in the same cohort. METHODS: We studied
      309 untreated hypertensive and 123 normotensive subjects. Aortic stiffness was
      evaluated by measuring the carotid-femoral pulse-wave velocity non-invasively.
      The endothelial nitric oxide synthase gene polymorphisms G10-T at intron 23
      (GIN23T) and G298-T at exon 7 (Glu298Asp) were determined in each subject.
      RESULTS: The distributions of genotypes and allele prevalences of the endothelial
      nitric-oxide synthase G10-T polymorphisms among hypertensive and normotensive
      subjects were similar. In contrast, the prevalence of the nitric oxide synthase
      298G allele was higher in the hypertensive group than it was among normotensive
      subjects. We found no association of the endothelial nitric oxide synthase
      genotypes with blood pressure levels or pulse-wave velocity for either
      population. CONCLUSIONS: The present results do not suggest that two common
      polymorphisms of the endothelial nitric oxide synthase gene are involved in the
      regulation of aortic stiffness in hypertensive and normotensive individuals. The
      higher prevalence of endothelial nitric oxide synthase 298G allele among
      hypertensives suggests that this gene is involved in essential hypertension but
      this observation needs further confirmation.

PMID- 9533415
TI  - Gene polymorphisms of the renin-angiotensin system in relation to hypertension
      and parental history of myocardial infarction and stroke: the PEGASE study.
      Projet d'Etude des Genes de l'Hypertension Arterielle Severe a moderee
      Essentielle.
AB  - OBJECTIVE: To investigate a possible involvement of polymorphisms of the renin
      angiotensin system in predisposition to moderate and severe hypertension and
      their relationship to parental histories of myocardial infarction and stroke.
      METHODS: Hypertensive cases (453 men, 326 women) were patients followed up by
      general practitioners for established hypertension. Inclusion criteria were an
      age of onset of hypertension < or = 60 years and a diastolic blood pressure > or
      = 105 mmHg without antihypertensive medication or > or = 100 mmHg under
      treatment. Normotensive controls were selected from population-based samples (362
      men) and during a preventative medicine visit (170 women). Polymorphisms of the
      angiotensinogen gene (AGT M235T and T174M), the angiotensin I converting enzyme
      gene (ACE I/D), and the angiotensin II type 1 receptor gene (AGT1R A1166C) were
      investigated. RESULTS: The AGTT235 allele prevalence was higher among male
      hypertensive cases than it was among controls (0.46 versus 0.40, P = 0.01) and a
      similar trend was observed with female cases whose hypertension had been
      diagnosed before they were aged 45 years (0.44 versus 0.38, P = 0.20). The AGT1R
      C1166 allele prevalence was higher among female hypertensives than it was among
      controls (0.30 versus 0.23, P = 0.03) but no such difference was observed for
      men. The AGT T174M and ACE I/D polymorphisms were not associated with
      hypertension. Hypertensive patients reporting a parental history of myocardial
      infarction before age 60 years had a higher prevalence of the ACE D allele than
      did those without such a parental history (0.68 versus 0.56, P = 0.01). The ACE D
      allele prevalence was also greater among patients reporting a parental history of
      stroke incidence before age 65 years (0.66 versus 0.57, P = 0.05). CONCLUSIONS:
      These results support the hypothesis that the AGT gene plays a role in
      predisposition to hypertension and that the ACE gene plays a role in
      predisposition to acute ischemic events.

PMID- 9533416
TI  - Progressive vascular damage in hypertension is associated with increased levels
      of circulating P-selectin.
AB  - OBJECTIVE: To assess whether increased shedding of adhesion molecules in plasma
      provides an index for endothelial damage in hypertension. DESIGN AND METHODS:
      Three groups of hypertensive patients with increasing severity of vascular damage
      were studied: 20 essential hypertensives, 21 atherosclerotic, renovascular
      hypertensives and four malignant hypertensives. Twenty healthy subjects were
      included as a control group. Levels of P-selectin, E-selectin, intracellular
      adhesion molecule 1, vascular cell adhesion molecule and von Willebrand factor in
      venous blood were measured, using sandwich-type enzyme-linked immunosorbent
      assay. RESULTS: For essential hypertensives a trend for increased P-selectin and
      E-selectin values compared with those in controls was observed (159+/-44 versus
      132+/-40 ng/ml, P = 0.062 and 40+/-13 versus 34+/-17 ng/ml, P = 0.055,
      respectively). P-selectin (210+/-84 ng/ml, P = 0.0021) and E-selectin (42+/-12
      ng/ml, P = 0.012) levels in renovascular hypertensives were significantly higher
      than those in healthy controls. There were no significant increases in
      circulating levels of intracellular adhesion molecule 1, vascular cell adhesion
      molecule and von Willebrand factor either in essential hypertensives or in
      renovascular hypertensives. Marked increases in circulating levels of adhesion
      molecules and von Willebrand factor relative to those in controls were observed
      in malignant hypertensives (P-selectin 634+/-332 versus 132+/-40 ng/ml, P =
      0.0004; vascular cell adhesion molecule 968+/-187 versus 493+/-139 ng/ml, P =
      0.0004; and von Willebrand factor 259+/-75 versus 130+/-72 U/dl, P = 0.016).
      CONCLUSIONS: Progression of vascular damage in essential, renovascular and
      malignant hypertension is associated with a rise in circulating levels of P
      selectins and, to a lesser extent, E-selectins, whereas levels of intracellular
      adhesion molecule 1, vascular cell adhesion molecule and von Willebrand factor
      are elevated only in diseases associated with acute severe vascular damage,
      including malignant hypertension. Our data suggest that selectins may be useful
      as indicators of vascular damage in hypertension.

PMID- 9533417
TI  - Single pericytes and pericytes in suspension are stimulated in a similar way by
      low-density lipoprotein.
AB  - BACKGROUND: Pericytes are regarded as the microvascular counterpart of smooth
      muscle cells and implicated in the regulation of blood pressure at the
      microvascular level. Ca2+ plays an important role in biochemical processes
      involved in blood pressure regulation and can be activated by low-density
      lipoprotein (LDL) cholesterol. OBJECTIVE: To determine whether stimulation either
      of single cells or of cells in suspension by LDL would produce any difference in
      the increase in cytosolic free calcium levels ([Ca2+]i). DESIGN AND METHODS:
      Single pericytes were loaded with 2 micromol/l of the Ca2+-sensitive dye Indo
      1/AM. The Indo-1 fluorescence was recorded at 405 nm (Ca2+-bound) and 485 nm
      (Ca2+-free) after stimulation with LDL. Pericytes in suspension were loaded with
      2 micromol/l of the Ca2+-sensitive dye FURA-2/AM. The FURA-2 fluorescence
      kinetics were recorded at 340-380 nm. Ratios of fluorescence at the two
      wavelengths were transformed to [Ca2+]i. RESULTS: Basal [Ca2+] levels appeared to
      be higher in single cells (148+/-13 nmol/l, n = 20) than they were in cells in
      suspension (128+/-8 nmol/l, n = 25; P= 0.0078). After stimulation with LDL the
      increase in [Ca2+]i in both systems was about 220% above baseline. A clear dose
      dependency was seen for both systems. CONCLUSIONS: Single pericytes and pericytes
      in suspension increase their [Ca2+]i after stimulation with LDL dose-dependently.
      Even though single-cell measurements revealed some technical limitations, their
      responses were comparable to those obtained in a cell suspension. In analogy to
      aortic smooth muscle cells, our results indicate that LDL might also play a blood
      pressure-regulatory role in the microvasculature.

PMID- 9533418
TI  - Lack of autonomic contributions to tonic nitric oxide-mediated vasodilatation in
      unanesthetized free-moving rats.
AB  - OBJECTIVE: To clarify the controversial issue of whether autonomic influences
      modulate vascular nitric oxide-mediated vasodilatation or even directly
      contribute to production of nitric oxide (NO) via nitroxidergic fibers. METHODS:
      Chronic venous and arterial catheters were implanted in Wistar-Kyoto rats (n =
      65) for continuous blood pressure measurement, drug administration and blood
      sampling. Tonic NO-dependent vasodilatation in the conscious free-moving animal
      was evaluated as the pressor response to inhibition of NO synthesis by
      intravenous L-monomethylarginine (a 100 mg/kg intravenous bolus plus 0.5 mg/kg
      per min infusion for 30 min). Experiments were performed under control
      conditions, chemical sympathectomy by 6-hydroxy-dopamine, ganglionic blockade by
      hexamethonium, and surgical denervation of sino-aortic baroreceptors. RESULTS:
      Baseline mean arterial pressure was 100+/-4 mmHg (mean +/- SEM) in control rats
      and 73+/-3, 62+/-5, and 105+/-10 mmHg in sympathectomized, ganglion-blocked, and
      denervated rats, respectively. The peak increase in mean arterial pressure after
      administration of L-monomethylarginine was 38+/-3 mmHg in control rats and 51+/
      3, 50+/-6, and 63+/-10 mmHg in sympathectomized, ganglion-blocked, and denervated
      rats, respectively. Epinephrine and norepinephrine levels in rats of separate
      groups of unanesthetized control, sympathectomized and ganglion-blocked animals
      were measured by high-performance liquid chromatography from an arterial blood
      sample, the results indicating drastic reductions in levels of both
      catecholamines in the ganglion-blocked (but not in the sympathectomized) rats
      compared with those in the control rats. CONCLUSIONS: Tonic NO-dependent
      vasodilatation can normally be maintained in the unanesthetized unrestrained rat
      irrespective of autonomic or humoral adrenergic influences.

PMID- 9533419
TI  - Sympathetic functions in NG-nitro-L-arginine-methyl-ester-induced hypertension:
      modulation by the renin-angiotensin system.
AB  - BACKGROUND: Nitric oxide and angiotensin II have been shown to attenuate cardiac
      beta-adrenergic inotropism. OBJECTIVE: To study sympathetic presynaptic and post
      synaptic functions after chronic nitric oxide synthesis blockade with NG-nitro-L
      arginine-methyl-ester (L-NAME, for 40 days) in association with renin-angiotensin
      system blockade (during the last 12 days) in order to evaluate the possible
      physiological interactions between these systems. METHODS: Haemodynamic
      parameters in conscious rats were assessed. Release of noradrenaline from
      isolated atria and cardiac beta-adrenergic-adenylyl cyclase pathway in rats of
      sham-treated and L-NAME-treated groups, with or without losartan or enalaprilat
      treatment, were assessed. RESULTS: L-NAME-treated rats developed a time-dependent
      increase in blood pressure associated with increased plasma adrenaline levels
      whereas plasma noradrenaline and cardiac catecholamine levels were similar to
      those in sham-treated rats. Field-stimulated release of noradrenaline, cardiac
      beta-adrenoceptor density and affinity and isoproterenol-stimulated formation of
      cyclic AMP were similar in sham and L-NAME-treated rats. However, Gpp(NH)p, NaF
      and forskolin-stimulated adenylyl cyclase activity were greater in L-NAME rats
      although Gs and Gi protein levels were similar in sham-treated and L-NAME-treated
      rats. Losartan and enalaprilat treatments exerted equipotent angiotensin-pressor
      response blockade and hypotensive effects whereas catecholamine levels were not
      altered. Interestingly, only losartan treatment acted to reduce the increased Gs
      adenylyl cyclase activity in L-NAME rats, without alteration of G protein levels.
      CONCLUSIONS: The nitric oxide synthase blockade-induced hypertension seems to be
      associated with increased adrenal-medullary system and renin-angiotensin system
      activities. The increased Gs-adenylyl cyclase activity after chronic inhibition
      of formation of nitric oxide suggests that nitric oxide plays a modulatory role
      in formation of cyclic AMP, to which angiotensin II seems to contribute through
      an angiotensin II type 1 receptor-mediated mechanism.

PMID- 9533420
TI  - Effect of neonatal sympathectomy on the development of structural vascular
      changes in angiotensin II-treated rats.
AB  - BACKGROUND: In a previous study, we found that neonatal sympathectomy prevented
      the development of angiotensin II (ANG II)-induced hypertension but not the
      development of structural changes in small mesenteric arteries. OBJECTIVES: To
      investigate further the dissociation between hypertension and structural vascular
      changes in sympathectomized ANG II-treated rats by extending morphometric
      measurements to include all segments of the mesenteric arterial tree. METHODS:
      Neonatally sympathectomized and sham-sympathectomized male Sprague-Dawley rats,
      aged 34 months, were administered 200 ng/kg per min ANG II subcutaneously for 4
      weeks. Sham-operated sympathectomized and sham-sympathectomized rats were
      controls. At the end of the treatment period the mesenteric circulation of rats
      was perfusion-fixed for morphometric measurements. RESULTS: Tail systolic blood
      pressure in ANG II-treated sham-sympathectomized rats increased by 47 mmHg (P <
      0.001); the increase of systolic blood pressure (11 mmHg) in ANG II-treated
      sympathectomized rats did not attain statistical significance. Sympathectomy
      alone increased the lumen and reduced the wall : lumen ratio of first- and second
      order branches of the superior mesenteric artery (hypotrophic outward
      remodeling). ANG II treatment increased the dimensions, wall thickness, and wall
      area of first- and second-order arteries (hypertrophic outward remodeling) and
      the wall : lumen ratio of small resistance arteries in sham-sympathectomized
      rats. Neonatal sympathectomy attenuated the development of structural changes in
      large arteries but had no effect on the development of structural changes in
      small arteries of ANG II-treated rats. CONCLUSION: Hypertension and sympathetic
      innervation appear to be contributing to the development of structural changes in
      large arteries of ANG II-treated rats because sympathectomy attenuated these
      changes. Structural changes in small arteries, on the other hand, appear to be
      due to a direct trophic effect of ANG II.

PMID- 9533421
TI  - Exaggerated natriuresis as a candidate intermediate phenotype in spontaneously
      hypertensive rats.
AB  - OBJECTIVE: To determine whether exaggerated natriuresis and exaggerated renal
      sympathoinhibition during volume loading constitute an intermediate phenotype in
      spontaneously hypertensive rats. DESIGN: The borderline hypertensive rat, the F1
      of a cross between a spontaneously hypertensive rat and a normotensive Wistar
      Kyoto rat, is a NaCl-sensitive model of genetic hypertension. In addition to
      hypertension, borderline hypertensive rats fed 8% NaCl food develop
      characteristic alterations in regulation of renal sympathetic nerve activity and
      neural regulation of renal function similar to those in the spontaneously
      hypertensive rat parent. Like the Wistar-Kyoto rat parent, borderline
      hypertensive rats fed 1% NaCl food remain normotensive and do not exhibit these
      alterations in renal sympathetic neural mechanisms. These renal sympathetic
      neural mechanisms constitute a complex quantitative trait that could represent an
      intermediate phenotype. METHODS: A backcross population, developed by mating
      borderline hypertensive rats with Wistar-Kyoto rats, was fed 8% NaCl food for 12
      weeks from age 4 to 16 weeks. Responses to intravenous isotonic saline volume
      loading (10% body weight/30 min) in 81 backcross rats chronically instrumented
      for measurement of mean arterial pressure, renal sympathetic nerve activity, and
      urinary sodium excretion were determined. RESULTS: Mean arterial pressure was 105
      180 mmHg and was not correlated to the magnitude either of the decrease in renal
      sympathetic nerve activity or of the increase in urinary sodium excretion during
      volume loading. CONCLUSIONS: These two aspects of the complex quantitative trait,
      exaggerated natriuresis and exaggerated renal sympathoinhibition during volume
      loading, are not part of an intermediate phenotype in spontaneously hypertensive
      rats.

PMID- 9533422
TI  - Gene expression of the renin-angiotensin system in human kidney.
AB  - BACKGROUND: Immunocytochemical studies have revealed that all components of the
      renin-angiotensin system are widely distributed in human tissues yet the
      information on the gene expression of the renin-angiotensin system in various
      types of cell remains scarce. OBJECTIVE: We explored the presence of a local
      renin-angiotensin system in human kidney. METHODS: We sought to determine the
      presence of messenger RNA (mRNA) encoding for renin, angiotensinogen, and
      angiotensin converting enzyme (ACE) in cultured human glomerular cells and human
      umbilical vein endothelial cells using a two-step polymerase chain reaction. The
      gene expression of the renin-angiotensin system in normal human kidney and in
      diseased kidney was studied by in-situ hybridization using synthetic
      oligonucleotides. RESULTS: By using a two-step polymerase chain reaction, renin,
      angiotensinogen, and ACE mRNA were found in cultured mesangial and epithelial
      cells but only ACE mRNA was present in human umbilical vein endothelial cells.
      Renin mRNA was detected in juxtaglomerular granular cells and also in glomerular
      and tubular epithelia in normal kidney by in-situ hybridization. A similar
      tubular, but not mesangial, distribution was found with angiotensinogen and ACE
      mRNA. In contrast, stronger signals for renin, angiotensinogen and ACE mRNA were
      detected in mesangial and epithelial cells of kidney tissues from hypertensive
      patients and from patients with renal pathology characterized by mesangial
      proliferation (immunoglobulin A nephropathy, diabetes mellitus, or lupus
      nephritis). CONCLUSIONS: That gene expression of the renin-angiotensin system
      occurs in resident glomerular cells supports the hypothesis that there is a local
      renin-angiotensin system in human kidney. Our findings support the previous
      speculation that the renin-angiotensin system could be a local factor involved in
      the progression of chronic renal failure and consequent development of
      hypertension.

PMID- 9533423
TI  - Effects of combination therapy with an angiotensin converting enzyme inhibitor
      and thiazide diuretic on insulin action in essential hypertension.
AB  - OBJECTIVE: To determine whether combination of an angiotensin converting enzyme
      inhibitor with a high dose of thiazide diuretic avoids adverse metabolic
      consequences of thiazide diuretics. DESIGN: Double-blind randomized crossover
      study of two 12-week treatment periods with captopril (up to 100 mg/day) either
      alone or in combination with 5 mg bendrofluazide given after a 6-week placebo run
      in period. Treatment periods were separated by a 6-week placebo washout period.
      SETTING: Outpatient clinics in greater Belfast. PATIENTS: Fifteen white non
      diabetic essential hypertensives (seven male) aged < 65 years recruited from
      general practices in greater Belfast. MAIN OUTCOME MEASURES: Systolic and
      diastolic blood pressures and peripheral and hepatic insulin action. RESULTS: Two
      patients failed to complete the study. Blood pressure was lowered (139/89+/-18/7
      mmHg combination versus 160/97+/-21/7 mmHg captopril; P < 0.001). Fasting insulin
      level was raised (7.9+/-3.6 mU/l combination versus 6.2+/-3.2 mU/l baseline; P <
      0.001). There were no differences between treatments for glucose, urate,
      cholesterol and triglyceride levels. Serum potassium level was lowered (3.8+/-0.4
      mmol/l combination versus 4.2+/-0.4 mmol/l captopril, P < 0.05). Postabsorptive
      endogenous glucose production was raised (10.8+/-1.7 micromol/kg per min
      combination versus 10.0+/-1.5 micromol/kg per min captopril; P < 0.01) and was
      greater than baseline (9.7+/-2.1 micromol/kg per min, P < 0.05). Suppression of
      glucose production by insulin was similar with both treatments. Exogenous glucose
      infusion rates required to maintain euglycaemia did not differ (32.4+/-7.6
      micromol/kg per min captopril, 32.7+/-6.2 micromol/kg per min combination, 31.5+/
      7.2 micromol/kg per min baseline). CONCLUSIONS: Combination therapy increased
      glucose production (compared with captopril alone), indicating hepatic insulin
      resistance. It cannot be assumed that combined preparations with angiotensin
      converting enzyme inhibitors will ameliorate adverse effects of high doses of
      thiazide diuretics on insulin action.

PMID- 9533424
TI  - Evaluation of changes in sympathetic nerve activity and heart rate in essential
      hypertensive patients induced by amlodipine and nifedipine.
AB  - OBJECTIVE: To compare the effects of amlodipine and nifedipine on heart rate and
      parameters of sympathetic nerve activity during the acute and chronic treatment
      periods in order to elucidate their influence on cardiovascular outcome. DESIGN:
      A randomized and single-blind study. METHODS: We performed 24 h ambulatory
      electrocardiography and blood pressure monitoring of 45 essential hypertensive
      inpatients. Plasma and urinary catecholamine levels were measured during the
      control (pretreatment) period, on the first day (acute period) and after 4 weeks
      (chronic period) of administration of amlodipine and of short-acting nifedipine
      or its slow-releasing formulation. The low-frequency and high-frequency power
      spectral densities and low-frequency: high-frequency ratio were obtained by heart
      rate power spectral analysis. RESULTS: Blood pressure was significantly and
      similarly reduced by administrations of amlodipine, short-acting nifedipine and
      slow-releasing nifedipine during the chronic period. The total QRS count per 24
      h, which remained constant during the chronic period of administration of slow
      releasing nifedipine and was increased by administration of nifedipine, was
      decreased by 2.8% by administration of amlodipine. Administration of amlodipine
      decreased the plasma and urinary norepinephrine levels during the chronic period,
      whereas the levels were significantly increased by administration of short-acting
      nifedipine and not changed by administration of slow-release nifedipine. Although
      low-frequency: high-frequency ratio was increased significantly by administration
      of short-acting nifedipine and slightly by administration of slow-releasing
      nifedipine, administration of amlodipine reduced it during the acute and chronic
      periods. CONCLUSIONS: Administration of amlodipine did not induce an increase in
      sympathetic nerve activity in essential hypertensive patients during the chronic
      period, suggesting that beneficial effects on essential hypertension can be
      expected after its long-term administration. Administration of slow-releasing
      nifedipine induces milder reflex sympathetic activation than does that of short
      acting nifedipine.

PMID- 9533426
TI  - Which extractant should be used for the screening and isolation of antimicrobial
      components from plants?
AB  - Freeze dried and finely ground leaves of two plants with known antimicrobial
      activity, Anthocleista grandiflora and Combretum erythrophyllum were extracted
      with acetone, ethanol, methanol, methylenedichloride, methanol/chloroform/water
      and water at a 1 to 10 ratio in each case. The quantity and diversity of
      compounds extracted, number of inhibitors extracted, rate of extraction, toxicity
      in a bioassay, ease of removal of solvent and biological hazard were evaluated
      for each extractant. An arbitrary scoring system was developed to evaluate the
      above parameters for the different extractants. Acetone gave the best results
      with these plants with an arbitrary value of 102 followed by
      methanol/chloroform/water (81), methylene dichloride (79), methanol (71), ethanol
      (58) and water (47). Four five minute sequential extractions of very finely
      ground A. grandiflora shaking at a high rate extracted 97% of the total
      antimicrobial activity.

PMID- 9533425
TI  - Cancer risk of hypertensive patients taking calcium antagonists.
AB  - OBJECTIVE: To measure rates of incident and fatal cancer in hypertensive patients
      taking calcium antagonists and to compare these with rates in three control
      groups. DESIGN: A retrospective analysis of cancer in patients of the Glasgow
      Blood Pressure Clinic prescribed either a calcium antagonist or other
      antihypertensive drugs (non-calcium antagonist group). Record linkage of the
      clinic with the West of Scotland Cancer Registry and with the Registrar General,
      Scotland provided information on incidence of cancer and on deaths and their
      causes. PATIENTS: 2297 patients were prescribed calcium antagonist and 2910 were
      prescribed antihypertensive drugs other than calcium antagonist. MAIN OUTCOME
      MEASURES: Relative risk of cancer, the ratio of observed to expected cancers in
      the calcium antagonist group, was estimated using expected values based on three
      control groups; namely the non-calcium antagonist group, a middle-aged population
      of Renfrew and Paisley and the West of Scotland population. RESULTS: There were
      134 incident cancers in the calcium antagonist group, representing relative risks
      of 1.02 [95% confidence interval (CI) 0.82-1.271 compared with the non-calcium
      antagonist group, 1.01 (95% CI 0.84-1.18) compared with Renfrew-Paisley controls
      and 1.02 (95% CI 0.85-1.19) compared with West of Scotland controls. Findings for
      cancer mortality were similarly negative. Risks were no higher for older
      patients. CONCLUSIONS: Our study lends no support to the suggestion that calcium
      antagonists cause cancer.

PMID- 9533427
TI  - Evaluation of the hepatoprotective and antioxidant activity of Boehmeria nivea
      var. nivea and B. nivea var. tenacissima.
AB  - In this study, the relationship between liver protective effects and antioxidant
      activity of Boehmeria nivea var. nivea (= B. nivea) and B. nivea var. tenacissima
      (= B. frutescens) was investigated. The water extracts of both plants exhibited a
      hepatoprotective activity against CCl4-induced liver injury. B. nivea var. nivea
      and B. nivea var. tenacissima, also showed anti-oxidant effects in FeCl2
      ascorbate induced lipid peroxidation in rat liver homogenate. Moreover, the
      active oxygen species scavenging potencies were evaluated by an electron spin
      resonance (ESR) spin-trapping technique. B. nivea var. tenacissima displayed
      better superoxide radical scavenging activity than B. nivea. Based on these
      findings, we suggest that in the liver protective and antioxidative effects of B.
      nivea var. nivea and B. nivea var. tenacissima, possibly involve mechanisms
      related to free radical scavenging effects.

PMID- 9533428
TI  - Effect of ambrein on smooth muscle responses to various agonists.
AB  - The pharmacological effects of ambrein (isolated from ambergris) on the
      contractile responses induced by some agonists in smooth muscle preparations were
      investigated. Ambrein in the concentration range of 10, 50 and 250 microg/ml
      decreased the spontaneous contraction of the isolated rabbit jejunum, rat uterus
      and guinea-pig vas deferens. Ambrein-induced antagonism to acetylcholine (Ach) in
      the guinea-pig ileum was abolished when the concentration of calcium chloride in
      the Tyrode's solution was increased to 5 mM/l. Furthermore, ambrein did not
      antagonise nicotine-induced contractions in the isolated rabbit jejunum or
      serotonin-induced contractions in the isolated guinea-pig ileum and vas deferens
      or the rat uterus. However, ambrein in the concentration range of 10, 50 and 250
      microg/ml antagonised prostaglandins (PGs) E2, D2, F2alpha, and oxytocin-induced
      contractions in the rat uterus in vitro. Ambrein also antagonised (+/-)
      noradrenaline and (-) adrenaline-induced contractions in the isolated guinea-pig
      vas deferens. It is concluded that ambrein-induced non-selective dose-dependent
      antagonism to the effects of some agonists (Ach, adrenaline, noradrenaline, PGs
      and oxytocin) in some smooth muscles may be due to the ability of this compound
      to interfere with the mobilisation of extracellular Ca2+ required for muscular
      contractions induced by these agonists.

PMID- 9533429
TI  - Hypoglycemic effect of the water extract of Piper sarmentosum in rats.
AB  - The hypoglycemic effect of the water extract of the whole plant of Piper
      sarmentosum Roxb. (Piperaceae, Thai name: Chaplu) was examined in normal and
      streptozotocin-diabetic rats. In an oral glucose tolerance test, a single oral
      administration of the water extract at doses of 0.125 and 0.25 g/kg significantly
      lowered the plasma glucose level in the normal rats. A reference drug,
      glibenclamide, at a dose of 5 mg/kg (per os, p.o.) also showed a significant
      hypoglycemic effect in the normal rats. In contrast, a single oral administration
      of the water extract at these doses and glibenclamide did not significantly lower
      the plasma glucose level in the diabetic rats. However, the repeated oral
      administration of the water extract at a dose of 0.125 g/kg for 7 days produced a
      significant hypoglycemic effect in the diabetic rats. Glibenclamide (5 mg/kg,
      p.o.) also caused significant hypoglycemia in the diabetic rats. These results
      demonstrated that the water extract of whole plant of Piper sarmentosum has a
      hypoglycemic effect in rats.

PMID- 9533430
TI  - Effects of ginseng total saponin on morphine-induced hyperactivity and
      conditioned place preference in mice.
AB  - A single or repeated administration of morphine in mice produced hyperactivity,
      conditioned place preference (CPP) and postsynaptic dopamine (DA) receptor
      supersensitivity. The hyperactivity induced by morphine was evidenced by
      measuring the enhanced ambulatory activity using a tilting-type ambulometer. CPP
      effects were evaluated assessing the increased time spent by the mice to morphine
      and the inhibition of CPP by the decreased time spent by the mice in the white
      compartment. Postsynaptic DA receptor supersensitivity in mice displaying a
      morphine-induced CPP was evidenced by the enhanced response in ambulatory
      activity to the DA agonist, apomorphine (2 mg/kg, s.c.). The intraperitoneal
      injection of ginseng total saponin (GTS) from the root of Panax ginseng C.A.
      Meyer (Araliaceae), prior to and during the morphine treatment in mice inhibited
      morphine-induced hyperactivity and CPP. GTS inhibited the development of
      postsynaptic DA receptor supersensitivity. A single dose administration of GTS
      also inhibited apomorphine-induced climbing behavior, showing the
      antidopaminergic action of GTS at the postsynaptic DA receptor. These results
      suggest that the development of morphine-induced CPP may be associated with the
      enhanced DA receptor sensitivity and that GTS inhibition of the morphine-induced
      hyperactivity and CPP may be closely related with the inhibition of dopaminergic
      activation induced by morphine.

PMID- 9533431
TI  - Effect of the Yang tonifying herbs on myocardial beta-adrenoceptors of
      hypothyroid rabbits.
AB  - New Zealand White female rabbits were randomly divided into three groups, each
      contained six rabbits, i.e. thyroidectomized and untreated rabbits (group 1),
      thyroidectomized rabbits treated by the Yang tonifying herbs (group 2) and sham
      thyroidectomized rabbits as controls (group 3). The myocardial beta-adrenoceptor
      density (Bmax) and affinity (Kd) of each group of rabbits were determined by
      radioligand binding assay technique on the thirtieth postoperative day and the
      data were handled by using a computer program of the Woolf plot with weight
      regression. Moreover, the serum levels of thyroxine (T4) and triiodothyronine
      (T3) of each group of rabbits were measured by radioimmunoassay technique and
      their heart rates (HR) were also recorded on the preoperative and thirtieth
      postoperative day. The results showed that the Bmax, T4, T3 and HR in group 1
      were lower significantly than that in group 3 (P < 0.01-0.001), but the change of
      Kd in group 1 was not significant; the deviation of the indices from the normal
      value in group 2 was less remarkably than in group 1 other than T4.

PMID- 9533432
TI  - Antiinflammatory and antinociceptive activities of extracts and isolated
      compounds from Stachytarpheta cayennensis.
AB  - The alcoholic and n-butanolic extracts of dried leaves of Stachytarpheta
      cayennensis (L.C. Rich) Vahl (Verbenaceae) was assessed in antiinflammatory and
      antinociceptive models. Intraperitoneal pretreatment with the dried extracts at
      doses ranging from 100 to 200 mg/kg, significantly inhibited carrageenin inducing
      edema formation. The active extracts were then fractionated and monitored with
      the same bioassay. The iridoid ipolamiide and the phenylethanoid glycoside
      acteoside were isolated from the active fraction and showed inhibitory effect on
      histamine and bradykinin induced contractions of guinea-pig ileum. The compounds
      also showed in vivo antiinflammatory activity when administered orally to rats
      mainly in the fourth hour after the administration of the phlogistic agent
      (70.22% and 93.99%, respectively). These results indicate that S. cayennensis
      shows antiinflammatory properties which seems to be due, at least partly, to the
      inhibition of bradyknin and histamine. The extracts also exhibited
      antinociceptive activity measured by the hot-plate test both i.p. and p.o. in
      doses ranging from 100 to 300 mg/kg.

PMID- 9533433
TI  - Activation of inducible nitric oxide synthase by Yongdam-Sagan-Tang in mouse
      peritoneal macrophages.
AB  - The objective of the current study was to determine the effect of Yongdam-Sagan
      Tang (YS-Tang) on the production of nitric oxide (NO). Stimulation of mouse
      peritoneal macrophages with YS-Tang after the treatment of recombinant interferon
      gamma (rIFN-gamma) resulted in increased NO synthesis. YS-Tang had no effect on
      NO synthesis by itself. When YS-Tang was used in combination with rIFN-gamma,
      there was a marked co-operative induction of NO synthesis in a dose-dependent
      manner. The optimal effect of YS-Tang on NO synthesis was shown 6 h after
      treatment with rIFN-gamma. This increase in NO synthesis was reflected as an
      increased amount of inducible NO synthase (iNOS) protein. NO production was
      inhibited by NG-monomethyl-L-arginine. The increased production of NO from rIFN
      gamma plus YS-Tang-stimulated cells was decreased by the treatment with
      staurosporin. In addition, synergy between rIFN-gamma and YS-Tang was mainly
      dependent on YS-Tang-induced tumor necrosis factor-alpha (TNF-alpha) secretion.
      All the preparations of YS-Tang were endotoxin free. These results suggest that
      the capacity of YS-Tang to increase NO production from rIFN-gamma-primed mouse
      peritoneal macrophages is the result of YS-Tang-induced TNF-alpha secretion.

PMID- 9533434
TI  - Cancer chemopreventive and therapeutic activities of red ginseng.
AB  - Red ginseng extract A and B are the active components of Panax ginseng. Red
      ginseng is a classical traditional Chinese medicine. Among Chinese herbs, red
      ginseng has been considered as one of the tonics. Many studies indicated that red
      ginseng could enhance immune function of the human body. The effects of red
      ginseng extracts on transplantable tumors, proliferation of lymphocyte, two-stage
      model and rat liver lipid peroxidation were studied. In a two-stage model, red
      ginseng extracts had a significant cancer chemoprevention. At 50-400 mg/kg, they
      could inhibit DMBA/Croton oil-induced skin papilloma in mice, decrease the
      incidence of papilloma, prolong the latent period of tumor occurrence and reduce
      tumor number per mouse in a dose-dependent manner. Red ginseng extract B could
      effectively inhibit the Fe2+/cysteine-induced lipid peroxidation of rat liver
      microsome, suggesting that red ginseng extract B has a stronger antioxidative
      effect than that of extract A. The results indicated that red ginseng extracts
      (50 approximately 400 mg/kg) could significantly inhibit the growth of
      transplantable mouse sarcoma S180 and melanoma B16. Red ginseng extracts A (0.5
      mg/ml) and B (0.1 and 0.25 mg/ml) might effectively promote the transformation of
      T lymphocyte, but there was no influence on lymphocyte proliferation stimulated
      by concanavalin A. This suggests that red ginseng extracts have potent tumor
      therapeutic activity and improve the cell immune system.

PMID- 9533435
TI  - Antibacterial activity of East African medicinal plants.
AB  - In an ethnopharmacological survey, extracts of the six East African medicinal
      plants Entada abyssinica (stem bark), Terminalia spinosa (young branches),
      Harrisonia abyssinica (roots), Ximenia caffra (roots), Azadirachta indica (stem
      bark and leaves), and Spilanthes mauritiana (roots and flowers) were tested
      against 105 strains of bacteria from seven genera (Staphylococcus, Enterococcus,
      Pseudomonas, Escherichia, Klebsiella, Salmonella, Mycobacterium). The minimum
      inhibitory concentration reached by 50% (MIC50%) and 90% (MIC90) of the strains
      for the extracts of E. abyssinica, T. spinosa, X. caffra, and A. indica (stem
      bark) ranged from 0.13-8 mg/ml and from 0.5 to > 8 mg/ml, respectively. Their
      minimum bactericidal concentration by 50% (MBC50%) and MBC90% were all between
      0.5 and > 8 mg/ml. H. abyssinica, A. indica (leaves), and S. mauritiana (roots
      and flowers) had MIC and MBC values > or = 8 mg/ml. Mycobacteria were not
      inhibited at extract concentrations of 0.5-2 mg/ml. It is concluded that plant
      extracts with low MIC and MBC values may serve as sources for compounds with
      therapeutic potency.

PMID- 9533437
TI  - Antimicrobial activity of aerial parts of Drosera peltata Smith on oral bacteria.
AB  - The antimicrobial activity of extracts of aerial parts of Drosera peltata Smith
      against oral bacteria was investigated using agar diffusion and dilution
      micromethods. The chloroformic extract, active against all the bacteria tested,
      showed the most significant antimicrobial properties. Plumbagin, isolated from
      the extract, is the active principle. Results obtained suggest that Drosera
      peltata extract could be used in the treatment of oral infectious diseases like
      dental caries and periodontitis.

PMID- 9533436
TI  - Screening of anti-diarrhoeal profile of some plant extracts of a specific region
      of West Bengal, India.
AB  - Ethanol extract of four different plants of the Khatra region of the Bankura
      district of West Bengal, India were evaluated for anti-diarrhoeal activity
      against different experimental models of diarrhoea in rats. The extracts of Ficus
      bengalensis Linn. (hanging roots), Eugenia jambolana Lam. (bark), Ficus racemosa
      Linn. (bark) and Leucas lavandulaefolia Rees (aerial parts) showed significant
      inhibitory activity against castor oil induced diarrhoea and PGE2 induced
      enteropooling in rats. These extracts also showed a significant reduction in
      gastrointestinal motility in charcoal meal tests in rats. The results obtained
      establish the efficacy of all these plant materials as anti-diarrhoeal agents.

PMID- 9533438
TI  - The role of the thymus in modulating gammadelta T cell suppressor activity during
      experimental Trypanosoma cruzi infection.
AB  - We have previously shown that splenic gammadelta T cells from young but not aged
      BALB/c mice possess suppressor activity in vivo and in vitro during the acute
      phase of Trypanosoma cruzi infection. The present work was undertaken to
      investigate the suppressor activity of gammadelta T cells from T. cruzi-infected
      euthymic or athymic mice and the role of the thymus in modulating non-adherent
      spleen cell suppressor activity during the acute phase of infection. Splenic
      gammadelta T cells from aged or athymic BALB/c mice reconstituted with total
      spleen cells or non-reconstituted did not exhibit suppressor activity when added
      to full allogeneic, mixed lymphocyte cultures. In contrast, splenic gammadelta T
      cells from young euthymic BALB/c mice showed suppressor activity in vitro.
      Thymectomy reduced the splenic gammadelta T cell suppressor activity of young
      BALB/c mice in a time-dependent manner, following a T. cruzi challenge. The
      continuous provision of thymocytes to aged mice, young thymectomized mice or
      total spleen cell-reconstituted athymic mice could re-establish the gammadelta T
      cell suppressor activity. Of particular significance was the observation that the
      depletion of gammadelta T cells during the acute phase of T. cruzi infection
      restored the capacity of these mice to mount a humoral immune response to a non
      related antigen such as ovalbumin. These results indicate that gammadelta T cells
      of extrathymic origin cannot mediate suppression and that the thymus has a role
      in the regulation of suppression during the acute phase of T. cruzi infection.

PMID- 9533439
TI  - The regulatory role of heat shock protein 70-reactive CD4+ T cells during rat
      listeriosis.
AB  - Protection against infection with Listeria monocytogenes depends primarily on
      Listeria-specific T cells. We show here that CD4+ TCR alphabeta+ T cells are
      capable of recognizing the mycobacterial heat shock protein (HSP) 70, that
      appears in the peritoneal cavity of F344 rats infected i.p. with L.
      monocytogenes. The HSP70-reactive CD4+ T cells recognized a peptide comprising
      234-252 residues as present in the 70 kDa HSP of Mycobacterium tuberculosis in
      the context of RT1.B MHC class II molecules. Analysis of TCR Vbeta gene
      expression with RT-PCR revealed that the HSP70-reactive CD4+ T cells
      predominantly used the Vbeta16 gene segment, whereas the heat-killed Listeria
      (HKL)-specific T cells expressed a diverse set of Vbeta gene segments. In
      contrast to the HKL-specific T cells producing IFN-gamma, the HSP70-reactive CD4+
      T cells produced TGF-beta1 and IL-10 but neither Th1- or Th2-type cytokines.
      Adoptive transfer with HSP70-reactive T cells rendered rats susceptible to
      listerial infection. Collectively, these results proposed that the HSP70-reactive
      CD4+ T cells appearing during rat listeriosis may be involved in termination of
      Th1 cell-mediated excessive inflammation after the battle against L.
      monocytogenes has been won.

PMID- 9533440
TI  - A three-dimensional model of the Fas/APO-1 molecule: cross-reactivity of anti-Fas
      antibodies explained by structural mimicry of antigenic sites.
AB  - Fas/APO-1 is a member of the tumor necrosis factor (TNF)/nerve growth factor
      receptor family. This cell surface protein, when associated with the Fas/APO-1
      ligand or specific mAb, elicits an apoptotic response in susceptible cells via an
      oligomerization of its intracellular domains, termed the'death domains'. We have
      previously mapped the epitopes of a panel of Fas/APO-1-reactive mAb to a series
      of linear portions of the Fas/APO-1 molecule. In order to gain a greater
      understanding of the mode of interaction of these antibodies with the Fas/APO-1
      antigen, we constructed a homology-based model of the extracellular portion of
      the molecule, based on the crystallographic coordinates of the TNF type I
      receptor. The model clearly demonstrates that the antibodies do not identically
      mimic the endogenous ligand to achieve their effect, but probably act in an
      analogous manner by recruiting Fas/APO-1 molecules into clusters which may lead
      to oligomerization of 'death domains'. Moreover, the apparent cross-reactivity
      observed for the monoclonal anti-Fas antibodies between different linear regions
      of the Fas/APO-1 molecule was found to be due, most likely, to the structural
      mimicry of these epitopes. Reduction of the Fas/APO-1-derived cross-reactive
      peptides by dithiothreitol completely abrogated their antigenic reactivity with
      the anti-Fas mAb CH-11, thus indicating that the establishment of intrapeptide
      disulfide bonds is critical for antigenic reactivity.

PMID- 9533441
TI  - Fc gammaRIIb inhibits both B cell receptor- and CD19-induced Ca2+ mobilization in
      Fc gammaR-transfected human B cells.
AB  - Fc gammaRIIb (CD32) controls antibody production by down-regulating cell
      activation, when co-clustered with B cell antigen receptors (BCR) in vivo, via
      immune complexes consisting of secreted IgG and antigen. Fc gammaRIIb-BCR co
      ligation in vitro was shown to inhibit the Ca2+ influx from the extracellular
      space, the mechanism of which is not fully understood. Human B cells express Fc
      gammaRIIb1 and Fc gammaRIIb2, differing only in a 19 amino acid long insert in
      the cytoplasmic tail of the former. To elucidate whether Fc gammaRIIb1 and Fc
      gammaRIIb2 isoforms show any difference in the down-regulation of B cells, we
      have studied the effect of co-clustering of BCR and Fc gammaRIIb1 or Fc
      gammaRIIb2 on the Ca2+ signaling in a Burkitt's lymphoma cell line, ST486,
      transfected with the two isoforms respectively. We have shown here, for the first
      time, that co-aggregation of BCR and Fc gammaRIIb may also inhibit Ca2+ release
      from the endoplasmic reticulum pool of human B cells. Both isoforms mediated this
      inhibition and the inhibitory effect depended on the ratio of BCR to Fc gammaRIIb
      cross-linking. In contrast to Fc gammaRIIb, the CD21/CD19 complex was shown to up
      regulate B cell response by lowering the activation threshold. We have shown here
      that co-clustering of Fc gammaRIIb with CD19 inhibited the CD19-induced Ca2+
      influx. Furthermore, the three party co-aggregation of Fc gammaRIIb with BCR and
      CD19 resulted in a decreased Ca2+ response, as compared to the BCR- plus CD19
      induced one, indicating that Fc gammaRIIb may inhibit CD19-induced enhancement of
      B cell activation. On the basis of these data we suggest that IgG-containing and
      C3d-fixing immune complexes may down-regulate the B cell response by interfering
      with both BCR- and CD19-mediated Ca2+ mobilization.

PMID- 9533442
TI  - Regulation of T cell autoreactivity to MHC class II by controlling CD80 (B7-1)
      expression on B cells.
AB  - Regulatory mechanisms of T cell autoreactivity to MHC class II molecules were
      studied in transgenic (Tg) mice with auto-I-Ak-reactive TCR alphabeta transgenes
      (designated as MS Tg mice). Our previous study revealed that the T cell tolerance
      established in autoreactive MS Tg mice was not due to either clonal deletion in
      the thymus, anergy or an active suppression in the periphery. We proposed a novel
      form of self tolerance termed 'clonal insufficiency', where autoreactive T cells
      were conditionally rendered unresponsiveness to self antigen in vivo, although
      retaining full potential reactivity in in vitro conditions. Here, we investigated
      the role of co-stimulatory molecules for the induction of self tolerance with
      'clonal insufficiency'. MS Tg mice were mated with CD80 (B7-1) Tg mice in which B
      cells exclusively and constitutively expressed CD80 molecules. Both MS Tg mice
      and CD80 Tg mice by themselves showed no evidence for activation of T cells and B
      cells, whereas MS x CD80 double-Tg mice with a H-2k background revealed an
      abnormal increase in the number of splenocytes and in the expression of
      activation markers (CD69 and CD25) on CD4 T cells in the spleen. These results
      indicated that the self tolerance established in MS Tg mice involved a down
      regulation of CD80 molecules on B cells in vivo, resulting in a failure of
      sufficient T-B interactions. In addition, the serum concentration of IL-10, one
      of the down-regulators of CD80 expression, was found to be increased
      significantly in MS Tg mice. The autoreactivity of MS Tg T cells detected in
      vitro was significantly blocked by recombinant IL-10. Thus, IL-10-mediated down
      regulation of CD80 on B cells was suggested to be involved in the clonal
      insufficiency in MS Tg mice in vivo.

PMID- 9533443
TI  - Pseudopeptide ligands for MHC II-restricted T cells.
AB  - The potential therapeutic use of peptides to activate or anergize specific T
      cells is seriously limited by their susceptibility to proteolytic degradation.
      Classically, peptides are stabilized by incorporation of non-natural
      modifications including main chain modifications. In the case of MHC II
      restricted peptides, the peptide backbone actively participates to the
      interaction with the MHC molecule and hence may preclude the peptidomimetic
      approach. We thus investigated whether a single amide bond modification
      influenced the peptide capacity to bind to a MHC II molecule and to stimulate
      specific T cells. Twenty pseudopeptide analogs of the I-Ed binder 24-36 peptide,
      whose sequence was derived from a snake neurotoxin, were obtained by replacing
      each amide bond of the peptide central part, by either a reduced psi[CH2-NH] or N
      methylated psi[CO-NMe] peptide bond. In agreement with the major interacting role
      played by the peptide backbone, several peptides displayed a low, if any,
      capacity to bind to the MHC II molecule and did not lead to T cell stimulation.
      However, one-third of the peptides were almost as active as the 24-36 peptide in
      I-Ed binding assays and one-fifth in T cell stimulation assays. Among them, two
      pseudopeptides displayed native-like activity. Good binders were not necessarily
      good at stimulating T cells, demonstrating that main chain modification also
      affected T cell recognition. We thus showed that a peptidomimetic approach could
      create a new type of MHC II ligand to control T cell responses.

PMID- 9533444
TI  - C1-esterase inhibitor blocks T lymphocyte proliferation and cytotoxic T
      lymphocyte generation in vitro.
AB  - We have previously shown that activated C1s complement and activated T cells
      cleave beta2-microglobulin (beta2m) in vitro leading to the formation of desLys58
      beta2m. This process can specifically be inhibited by C1-esterase inhibitor (C1
      inh). Furthermore we showed that exogenously added desLys58 beta2m in nanomolar
      amounts to a one-way allogenic mixed lymphocyte culture (MLC) increased the
      endogenous production of IL-2 and the generation of allo-specific cytotoxic T
      lymphocytes. C1-inh was purified from fresh human plasma and added to human or
      murine MLC and mitogen-stimulated lymphocyte cultures grown in the presence of
      complement-inactivated serum. Read-outs were cell proliferation, lymphokine
      production and development of T cell-mediated cytotoxicity. We found that
      addition of C1-inh to MLC and mitogen-exposed murine and human lymphocyte
      cultures inhibited proliferation, the development of allospecific cytotoxic
      activity, and changed the endogenous production of IL-2, IL-4, IL-10, IL-12 and
      IFN-gamma. These data clearly demonstrate a regulatory function of C1-inh on T
      cell-mediated immune functions.

PMID- 9533445
TI  - Regulation of programmed cell death following T cell activation in vivo.
AB  - Activation of T cell hybridomas in vitro induces rapid Fas-Fas ligand (FasL)
      mediated programmed cell death (apoptosis). In contrast, T cells activated by
      antigen or superantigen in vivo undergo a population expansion and then decline
      due to Fas-FasL-mediated activation-induced apoptosis (AIA). We asked how T cells
      activated by antigen in vivo proliferated before undergoing apoptosis. Two
      possibilities were analyzed: either (i) the apoptosis program was not 'turned on'
      or (ii) was 'blocked' during the period of cellular proliferation in vivo. Data
      presented in this manuscript support the second of these possibilities. CD4+ T
      cells activated in vivo were resistant to anti-fas-mediated apoptosis until 48 h
      following staphylococcal enterotoxin B (SEB) administration, despite the fact
      that activated proliferating T cells expressed high levels of Fas (CD95) antigen
      and many 'apoptosis genes' were induced within 24 h of SEB administration. The
      analysis of the expression patterns of 'apoptosis genes' during the T cell
      activation further suggested that temporal blockade of AIA may be due to the
      induction of apoptosis-preventing genes, such as bag-1.

PMID- 9533446
TI  - Biochemical analysis of the CD45-p56(lck) complex in Jurkat T cells lacking
      expression of lymphocyte phosphatase-associated phosphoprotein.
AB  - In human and mouse lymphocytes the protein tyrosine phosphatase CD45, a key
      molecule involved in T cell activation, non-covalently associates with the
      tyrosine kinase p56(lck) and lymphocyte phosphatase-associated phosphoprotein
      (LPAP), a 32 kDa phosphoprotein of unknown function. In order to gain insight
      into the function of LPAP we have generated an LPAP-deficient Jurkat variant by
      means of antisense strategies. Analysis of the CD45-p56(lck) molecular complex in
      this cell line revealed that loss of LPAP does not alter the expression or the
      enzymatic activity of CD45 or p56(lck). In addition, the association between CD45
      and p56(lck) is not affected in LPAP-deficient T cells. These data suggest that
      LPAP does not regulate the enzymatic activity of CD45 or p56(lck) and is not
      required for the association between these two proteins. In order to identify
      polypeptides that preferentially associate with LPAP we established a Jurkat
      variant expressing a chimeric receptor which was composed of the extracellular
      portion of the human HLA-A2.1 molecule and the full-length LPAP protein.
      Comparative two-dimensional analysis of CD45 and HLA-A2 immunoprecipitates
      obtained from these cells following metabolic labeling resulted in the
      identification of a 43 kDa protein that preferentially associates with LPAP under
      mild detergent conditions.

PMID- 9533447
TI  - Novel Fas (CD95/APO-1) mutations in infants with a lymphoproliferative disorder.
AB  - Fas is an apoptosis-signaling receptor important for homeostasis of the immune
      system. In this study, Fas-mediated apoptosis and Fas mutations were analyzed in
      three Japanese children from two families with a lymphoproliferative disorder
      characterized by lymphadenopathy, hepatosplenomegaly, pancytopenia,
      hypergammaglobulinemia and an increase in TCR alphabeta+ CD4- CD8- T cells.
      Apoptosis induced by anti-Fas mAb was defective in both activated T cells and B
      cells, and granulocytes from these patients. Truncated Fas receptor lacking the
      cytoplasmic death domain caused by a point mutation in the splice region of
      intron 7 were demonstrated in two siblings. A homozygous point mutation in the
      splice acceptor of intron 3 was found in the Fas gene of the third patient, which
      resulted in the skipping of exon 4 and complete loss of Fas expression.
      Corresponding to these mutations, soluble Fas concentrations were decreased and
      reciprocally soluble Fas ligands were increased in patients' sera. Interestingly,
      co-stimulation by immobilized anti-Fas mAb in T cells from the two siblings was
      comparable to that seen in normal T cells. These results suggest that Fas
      mediated apoptosis plays a pivotal role in immunological homeostasis in vivo,
      especially regarding clonal deletion of immune cells in humans.

PMID- 9533449
TI  - Six unrelated HLA-DR-matched adults recognize identical CD4+ T cell epitopes from
      influenza A haemagglutinin that are not simply peptides with high HLA-DR binding
      affinities.
AB  - Influenza A/Beijing/32/92 (H3N2) haemagglutinin (HA)-specific short-term CD4+ T
      cell lines were generated from six unrelated HLA-DR0701, 1501 positive adults
      (aged 27-60 years) 3 months following administration of an influenza subunit
      vaccine containing HA A/Beijing/32/92. Epitope recognition was examined using 118
      HA A/Beijing/32/92-specific 16mer peptides which overlapped by 11 residues and
      which spanned the entire molecule. Following influenza vaccination the donors
      recognized identical HA peptides. The selected peptides represented HA regions
      which have been free from extensive drift mutation since the emergence of human
      H3N2 influenza A strains. Using DAP DR7.0701 cells (a murine cell line expressing
      HLA-DR0701) as antigen-presenting cells the majority of CD4+ T cell responses
      were shown to be HLA-DR0701 restricted. The relationship between HA peptide
      recognition and relative strength of HA peptide-HLA-DR0701 binding was then
      explored in a competition assay with biotinylated CLIP peptide. Although peptides
      representing dominant HA epitopes bound to DR0701, the relationship between
      relative strength of binding and immunodominance was complex, and many strongly
      binding peptides, particularly those with glycosylation sites and showing inter
      strain variation, were not recognized. These results illustrate the control HLA
      class II exerts over CD4+ T cell HA epitope selection in unrelated adult humans.
      Immunodominance appears not to be directly related to the relative strength of HA
      peptide-HLA class II binding, and thus reflects complex interactions between
      antigen processing, intracellular competition for HLA binding, TCR repertoires
      and repeated exposure to different strains of influenza A viruses.

PMID- 9533448
TI  - A novel domain in the CD30 cytoplasmic tail mediates NFkappaB activation.
AB  - About 100 amino acid residues in the C-terminal region are conserved among human,
      rat and murine CD30, a member of the tumor necrosis factor receptor (TNFR)
      superfamily, and can be separated into three subdomains with relatively higher
      conservation (D1, D2 and D3). Activation of NFkappaB by CD30 was shown to be
      mediated through interaction of TNFR-associated factor (TRAF) 1, 2 and 5 with the
      D2 and D3 subdomains. However, the function of the other conserved subdomain, D1,
      remained to be determined. Deletion of the D2 and D3 subdomains abolished
      interactions with TRAF2 and 5 but it did not affect NFkappaB activation. Reporter
      gene assays using deletion and mutant constructs of CD30 revealed that the D1
      subdomain is sufficient for NFkappaB activation, without interaction with TRAF2
      or 5, and that each subdomain alone can activate NFkappaB. Electrophoretic
      mobility shift assays revealed constitutive and CD30-induced NFkappaB activation
      in stable transformants of 293 cells expressing CD30 or a deletion mutant lacking
      D2 and D3 subdomains. Deletion of C-terminal 19 amino acid residues of the D1
      subdomain abolished activation of NFkappaB. Substitution of alanine for one of
      the two threonine residues (amino acid position 524 and 529), one of which is a
      potential phosphorylation site in the D1 subdomain, also abolished the NFkappaB
      activation. Overexpression of the TRAF domain of TRAF2 or 5 had a dominant
      negative effect on the NFkappaB activation mediated by the D1 subdomain, thereby
      suggesting involvement of TRAF proteins in the signaling. Thus, the C-terminal
      100 amino acid region of CD30 is composed of three independent functional
      subdomains, two of which contain binding sites for TRAF proteins. A novel domain
      in the cytoplasmic tail mediates NFkappaB activation, without direct interaction
      of TRAF2 or 5. Our observations suggest involvement of an unknown TRAF protein(s)
      in the signal transduction pathway of CD30.

PMID- 9533450
TI  - Activation of the extracellular signal-regulated kinase pathway is differentially
      required for TCR-stimulated production of six cytokines in primary T lymphocytes.
AB  - The extracellular signal-regulated kinase (ERK) signaling pathway is strongly
      activated in response to TCR stimulation in normal T cells. However, the extent
      to which activation of the ERK pathway is necessary for TCR-stimulated cytokine
      production is not clear. We have addressed this question by use of two separate
      methods to interfere with TCR activation of the ERK cascade. The first approach
      utilized transient expression of a catalytically inactive form of mitogen
      activated/ERK 1 (CI-MEK1), while the second involved using the MEK1- and MEK2
      specific inhibitor PD98059 to block ERK activation by the TCR. In order to assess
      the requirement for ERK activation in T cell cytokine production, we have
      measured the effect of ERK inhibition upon the production of six cytokines, IL-3,
      IL-4, IL-5, IL-10, granulocyte macrophage colony stimulating factor (GM-CSF) and
      IFN-gamma, by newly activated normal mouse T cells in response to TCR
      stimulation. The results of experiments using both methods to block ERK
      activation have revealed a requirement for intact ERK signaling for the full
      elicitation of TCR-stimulated cytokine production. Dose-response analyses using
      the MEK inhibitor PD98059 showed that the TCR-stimulated production of all
      cytokines measured was affected by this treatment. However, the production of IL
      3 and IL-4 was only partially dependent upon ERK activation, whereas IL-5, IL-10,
      IFN-gamma and GM-CSF production was severely affected by diminished ERK
      activation. We conclude that the ERK pathway is differentially involved in the
      activation of different cytokine genes in normal T cells.

PMID- 9533451
TI  - Dynamic regulation of gastric autoimmunity by thyroid hormone.
AB  - Neonatal thymectomy (NTX) of BALB/c mice between days 1 and 3 post-birth leads to
      a high incidence of autoimmune gastritis involving T cells and autoantibodies.
      Although progress has been made in understanding various immunological events
      associated with that disease process, much remains to be learned about the
      regulatory factors which control autoimmune gastritis. In this study we have
      examined the potential for neuroendocrine hormones of the hypothalamus-pituitary
      thyroid (HPT) axis to alter the outcome of experimental autoimmune gastritis in
      NTX mice. As reported here, thyroxine administered to young adult NTX mice during
      an active phase of disease development dramatically reduced the incidence of
      gastritis and the overall severity of disease, and lowered the levels of anti
      parietal cell antibodies. In contrast, treatment of young NTX mice with thyroxine
      or other HPT hormones prior to the onset of disease had no beneficial effect on
      gastritis, but instead resulted in significantly higher anti-parietal cell
      antibody levels compared to non-hormone-treated NTX mice or to NTX mice treated
      as adults. Reverse transcriptase spectratype analyses of 22 Vbeta gene junctional
      sites revealed pronounced oligoclonality and limited junctional diversity in
      stomach lymphocytes from untreated NTX mice compared to normal mice or thyroxine
      treated NTX mice. These findings identify a set of dynamic immune-endocrine
      interactions, linked to critical development-dependent events, that are involved
      in the expression and regulation of peripheral autoimmunity.

PMID- 9533452
TI  - Does the IL-2 receptor alpha chain induced on dendritic cells have a biological
      function?
AB  - The IL-2 receptor (IL-2R) alpha chain (CD25), but not the IL-2R beta chain, is
      induced on dendritic cells (DC) by brief periods of culture. To test if this IL
      2R alpha is important for DC function, DC were isolated from the spleens of
      mutant mice with the IL-2R alpha gene disrupted and compared with normal DC for
      ability to stimulate proliferation of allogeneic CD4 and CD8 T cells in culture.
      The IL-2R alpha null DC and the normal DC produced nearly identical proliferative
      responses from CD4 and from CD8 T cells. When the CD8 alpha+ and CD8 alpha-
      subsets of the IL-2R alpha null DC were separated, they also produced
      proliferative responses similar to that of their normal DC counterparts. Overall
      there was no evidence that the inducible IL-2R alpha on DC was required for DC
      development, for stimulation of T cells or for regulation of T cell responses.

PMID- 9533453
TI  - Molecular mechanisms involved in receptor editing at the Ig heavy chain locus.
AB  - In receptor editing, a phenomenon that has recently come to light and into favor,
      a rearranged VDJ or VJ gene segment encoding a variable region of an Ig chain is
      replaced by another. In this commentary, the molecular mechanisms involved in the
      editing process are examined in some detail. Editing is most likely mediated by
      the same V(D)J recombinase activity responsible for the formation of the original
      VDJ or VJ segment. An embedded heptamer, which is present near the 3' end of many
      VH elements, is used as the recombination signal sequence at the Ig heavy chain
      locus. It has been postulated that the mediation of receptor editing is the
      evolutionary force maintaining the embedded heptamer. Some of the evidence for
      and against this hypothesis is discussed.

PMID- 9533454
TI  - Albendazole.

PMID- 9533455
TI  - Pharmacodynamic properties of HMR 3647, a novel ketolide, on respiratory
      pathogens, enterococci and Bacteroides fragilis demonstrated by studies of time
      kill kinetics and postantibiotic effect.
AB  - The pharmacodynamic properties of a novel ketolide (a new class of macrolide),
      HMR 3647, were investigated by studying time-kill kinetics and postantibiotic
      effect (PAE). The time-kill kinetics were studied at two inocula against three
      strains each of Staphylococcus aureus, Haemophilus influenzae, Moraxella
      catarrhalis, Streptococcus pneumoniae, Streptococcus pyogenes, Enterococcus
      faecalis, Enterococcus faecium and Bacteroides fragilis. The PAEs of HMR 3647
      were also investigated on these organisms at concentrations equivalent to 1, 4
      and 10 x MIC. The time-kill kinetic data demonstrated that HMR 3647 is
      predominantly bacteriostatic and only slowly bactericidal at higher
      concentrations. HMR 3647 exhibited a significant PAE with all strains studied,
      ranging from 1.2 h to 8.2 h at 10 x MIC. The bacteriostatic activity and
      significant PAE demonstrated by HMR 3647 are similar to those previously obtained
      with other macrolides.

PMID- 9533456
TI  - Effect of subinhibitory concentrations of vancomycin, cefazolin, ofloxacin, L
      ofloxacin and D-ofloxacin on adherence to intravascular catheters and biofilm
      formation by Staphylococcus epidermidis.
AB  - Staphylococcus epidermidis is the preeminent cause of nosocomial bacteraemia and
      infection of prosthetic medical devices. Bacterial adherence to biomaterial is a
      crucial early event in the pathogenesis of these infections. Antibiotics affect
      bacterial adherence to eukaryotic cells, capsule formation and biofilm
      production. However, results from studies involving coagulase-negative
      staphylococci are equivocal. In this study, the in-vitro adherence of
      radiolabelled bacteria was assayed to determine the effect of sublethal
      concentrations of a number of antibiotics on the attachment of four strains of S.
      epidermidis, with well-characterized adherence profiles, to intravascular
      catheters. The effect of antibiotics on biofilm production by S. epidermidis was
      assayed using a quantitative spectrophotometric assay. Although there was some
      strain-to-strain variability, none of the tested antibiotics affected bacterial
      attachment. However, treatment with cefazolin or vancomycin resulted in a
      significant decrease in biofilm elaboration. These data suggest that bacterial
      attachment by S. epidermidis, the initiating event associated with prosthetic
      device infection, cannot be prevented by subtherapeutic levels of
      fluoroquinolone, glycopeptide or beta-lactam antibiotics. However, later
      aggregative stages of adherence, associated with biofilm production, may be
      influenced by cell wall-active agents such as cefazolin and vancomycin.

PMID- 9533457
TI  - Antibiotic-induced release of endotoxin: in-vitro comparison of meropenem and
      other antibiotics.
AB  - The influence of meropenem, a new carbapenem antibiotic, on cell morphology and
      in-vitro lipopolysaccharide (LPS) release from Escherichia coli was compared with
      that of imipenem, ceftazidime, tobramycin and ciprofloxacin. Free and cell
      associated LPS was quantified by means of a capture ELISA method based on the
      recognition of E. coli LPS by monoclonal antibodies. Microscopically, meropenem
      was found to induce spheroplast formation similar to that seen with imipenem,
      while ceftazidime and ciprofloxacin induced filament formation. Free and cell
      associated LPS levels were low in the presence of meropenem, imipenem,
      ciprofloxacin and tobramycin, but high in the presence of ceftazidime. Reduced
      endotoxin release appears to be a common property of carbapenem antibiotics.
      Morphological changes in bacteria in the presence of antibiotics do not predict
      their LPS-liberating effect since ciprofloxacin induced low levels of LPS despite
      causing filament formation.

PMID- 9533459
TI  - Molecular basis of clarithromycin activity against Mycobacterium avium and
      Mycobacterium smegmatis.
AB  - Clarithromycin, the 6-O-methyl derivative of erythromycin, is approved for
      treatment of Mycobacterium avium infections and for prophylaxis in patients at
      risk. Since clarithromycin is more active against mycobacteria than the parent
      compound, erythromycin, we evaluated the interaction of erythromycin and
      clarithromycin with cells and ribosomes isolated from M. avium and Mycobacterium
      smegmatis. The MIC of clarithromycin was 32 and 64 times lower than that of
      erythromycin for M. smegmatis and M. avium, respectively. The cellular uptake
      rate for clarithromycin was two- to five-fold faster than for erythromycin, and
      cell-associated clarithromycin reached a plateau two-fold higher than that of
      erythromycin after 3 h. Energy was not required for uptake. Fractionation of cell
      associated clarithromycin yielded 12% in the walls, 21% bound to ribosomes, with
      the remainder being lost during work-up. In addition, three- to six-fold more
      clarithromycin was associated with the isolated cell integument compared with
      erythromycin. The Kd for clarithromycin binding to ribosomes was 2.9- and 3.5
      fold tighter for M. smegmatis and M. avium, respectively, than for erythromycin,
      due mainly to a slower off-rate. The log partition coefficients of the non
      ionized form (log Pu) for clarithromycin and erythromycin were 3.24 and 2.92,
      respectively. Thus clarithromycin is more hydrophobic than erythromycin. This
      would favour more rapid diffusion within and across hydrophobic regions of the
      cell integument, since once a solute saturates a membrane the net flux across the
      membrane must equal the net flux within the membrane as dictated by diffusion. We
      conclude that the lower MIC of clarithromycin for M. avium and M. smegmatis is
      due to a combination of increased cellular uptake, the major factor, possibly
      through a peripheral hydrophobic layer, and increased binding affinity to
      ribosomes.

PMID- 9533458
TI  - Flavodoxin-dependent pyruvate oxidation, acetate production and metronidazole
      reduction by Helicobacter pylori.
AB  - Helicobacter pylori flavodoxin was purified to homogeneity from cell extracts of
      strain NCTC 11637. The molecular weight of the protein was estimated by gel
      electrophoresis to be 18 kDa. Oxidized flavodoxin showed an absorption spectrum
      with maxima at 378 nm and 453 nm, and it was reduced to a neutral form of flavin
      semiquinone by the electrons generated in the oxidation of pyruvate. This
      coenzyme A dependent pyruvate:flavodoxin oxidoreductase activity of H. pylori was
      also detected as a reduction of methyl viologen or cytochrome c by bacterial
      extracts. The apparent Km of pyruvate was 310 microM. Anaerobically incubated
      bacteria (10[9]) of strain NCTC 11637 produced acetate (96 +/- 16 nmol/h) from
      pyruvate concomitantly reducing metronidazole (17 +/- 5 nmol/h). In anaerobic
      conditions both sensitive and resistant H. pylori strains reduced metronidazole,
      and there was a significant positive correlation between acetate production and
      metronidazole activation (r = 0.77, P < 0.01, n = 11). In the presence of
      atmospheric oxygen, H. pylori excreted twice as much acetate but metronidazole
      was not activated. These results suggest that the pyruvate:flavodoxin
      oxidoreductase complex catalyses pyruvate oxidation in H. pylori. Electrons
      generated in this reaction are transferred to flavodoxin and under anaerobic
      conditions further to metronidazole (imidazoles) thus reducing the drug to its
      bactericidal form.

PMID- 9533460
TI  - Contribution of overproduced chromosomal beta-lactamase and defective outer
      membrane porins to resistance to extended-spectrum beta-lactam antibiotics in
      Serratia marcescens.
AB  - Using clinical strains of Serratia marcescens with low and high resistance to
      extended-spectrum beta-lactam antibiotics, the relative contribution of
      chromosomal beta-lactamase and defective outer membrane porins to resistance was
      determined. Low-level resistance was caused by overproduced beta-lactamase alone.
      High-level resistance was due to beta-lactamase overproduction and defects of
      porin OmpF or OmpF and OmpC. Overproduction of beta-lactamase in bacteria with
      both degrees of resistance was eliminated by transformation with cloned ampD+,
      the gene (from Escherichia coli) for negative modulation of beta-lactamase
      induction. In transformants of highly resistant bacteria with normally low and
      inducible beta-lactamase production, the remaining porin defects alone imparted
      only minimal resistance to extended-spectrum beta-lactam antibiotics.

PMID- 9533461
TI  - In-vitro antiproliferative effects and mechanism of action of the bis-triazole
      D0870 and its S(-) enantiomer against Trypanosoma cruzi.
AB  - We investigated the in-vitro antiproliferative effects and mechanism of action of
      both enantiomers of the bis-triazole derivative ICI 195,739 against epimastigotes
      and amastigotes of Trypanosoma cruzi, the aetiological agent of Chagas' disease.
      It has recently been shown that the R(+) enantiomer, D0870, can induce radical
      parasitological cure in murine models of the acute and chronic forms of the
      disease. D0870 dose-dependently affected the growth rate of the epimastigote form
      (IC50 = 0.1 microM; MIC = 1-3 microM). The S(-) enantiomer was much less active
      (IC50 = 3 microM). Growth arrest and cell lysis induced by D0870 coincided with
      the complete depletion of endogenous 4,14-desmethyl sterols and their replacement
      by 4,14-trimethyl and dimethyl sterols. The S(-) enantiomer produced
      qualitatively similar changes but to a lesser extent. D0870 inhibited the
      incorporation of radioactivity from [2-14C]acetate into the epimastigote's 4,14
      desmethyl sterols with an IC50 of 50 nM while the corresponding concentration for
      the S(-) enantiomer was 3 microM. D0870 eradicated the intracellular (amastigote)
      form of the parasite from cultured Vero cells at 10 nM; a 100-fold higher
      concentration of the S(-) enantiomer was required to produce a similar effect,
      and deleterious effects of the host cells were observed at > 100 nM. At the MIC
      of D0870 the endogenous amastigote sterols (ergosta-7-en-3beta-ol, 24-ethyl
      cholesta-7-en-3beta-ol and ergosta-7, 24(24[1])-dien-3beta-ol) were also largely
      replaced by lanosterol and 24-methyl-dihydrolanosterol. Combinations of D0870 and
      inhibitors of sterol delta24(25) sterol methyltransferase (such as 22,26
      azasterol and 24(R,S),25-epiminolanosterol) acted synergically against the
      intracellular forms. Taken together these results indicate that, although both
      enantiomers have anti-T. cruzi activity, the specific activity of the R(+)
      enantiomer (D0870) is nearly two orders of magnitude higher than that of its S(-)
      analogue. However, as the in-vitro activity of D0870 is comparable to that of
      standard azoles, such as ketoconazole, its remarkable in-vivo antiparasitic
      activity may only be explained by its particular pharmacokinetic properties.

PMID- 9533462
TI  - Sensitivity to sparfloxacin and other antibiotics, of Streptococcus pneumoniae,
      Haemophilus influenzae and Moraxella catarrhalis strains isolated from adult
      patients with community-acquired lower respiratory tract infections: a European
      multicentre study. SPAR Study Group. Surveillance Programme of Antibiotic
      Resistance.
AB  - A survey of resistance to sparfloxacin was carried out in ten European countries,
      namely Slovakia, France, Germany, Great Britain, Hungary, the Republic of
      Ireland, Italy, The Netherlands, Portugal and Spain. Respiratory samples were
      collected from 4297 patients with lower respiratory tract infections and cultured
      for the presence of Streptococcus pneumoniae, Haemophilus influenzae and
      Moraxella catarrhalis. Altogether 2101 strains were isolated and tested for their
      susceptibility to sparfloxacin, ciprofloxacin, erythromycin, tetracycline and
      penicillin G (S. pneumoniae) or amoxycillin (H. influenzae and M. catarrhalis).
      Each country tested strains using methods commonly used in that country, and with
      breakpoints selected based on those used in that country. Penicillin resistance
      in pneumococci was seen in those countries in which it had been reported
      previously, namely Spain, France and Hungary. Only four strains of pneumococci
      were resistant to sparfloxacin (MIC > or = 2 mg/L), while ciprofloxacin-resistant
      strains were isolated more frequently, particularly in the Republic of Ireland
      and Hungary. Almost all of the strains of H. influenzae tested were resistant to
      erythromycin, (MIC50 > or = 4 mg/L), but all strains were highly sensitive to
      sparfloxacin (MIC90 < or = 0.06 mg/L). The number of strains of H. influenzae
      producing beta-lactamase varied between countries, whereas most strains of M.
      catarrhalis produced beta-lactamase. In M. catarrhalis, erythromycin and
      tetracycline resistance was rare, but sensitivity to amoxycillin varied.
      Sparfloxacin was particularly active against H. influenzae and M. catarrhalis,
      and was the most active compound tested. Overall, the activity of sparfloxacin
      was greater than that of ciprofloxacin against all three pathogens, and
      resistance to it was rare.

PMID- 9533463
TI  - Antibiotic accumulation and membrane trafficking in cystic fibrosis cells.
AB  - Cystic fibrosis (CF) results from mutations in the gene encoding the CF
      transmembrane conductance regulator (CFTR) which is a regulated chloride channel.
      The deltaF508 mutation prevents the post-translational glycosylation and membrane
      insertion of the protein. Severe disease follows, with the formation of a viscous
      mucus and subsequent chronic bacterial infection of the lungs, necessitating
      frequent, and often long, periods of antibiotic treatment. The pharmacokinetics
      of antibiotics in CF patients are abnormal, with lower blood serum levels and
      higher clearance rates which have never been satisfactorily explained. We found
      that accumulation of gentamicin in nasal polyp tissue non-CF cells was subject to
      regulation by the effectors and inhibitors of CFTR function; regulation was lost
      in deltaF508 CF cells and accumulation was more than doubled because of the
      inhibition of exocytosis.

PMID- 9533464
TI  - In-vitro and in-vivo antibacterial activity of CFC-222, a new fluoroquinolone.
AB  - CFC-222 is a novel fluoroquinolone with potent and broad-spectrum antibacterial
      activity. The in-vitro and in-vivo activities of CFC-222 were compared with those
      of ciprofloxacin, ofloxacin, lomefloxacin and sparfloxacin. Against gram-positive
      bacteria such as Staphylococcus aureus (quinolone-susceptible and quinolone
      resistant), Staphylococcus epidermidis, Streptococcus pneumoniae and Enterococcus
      faecalis, CFC-222 was more active than ciprofloxacin and similar to sparfloxacin.
      Against gram-negative bacteria, including Enterobacteriaceae, the in-vitro
      activity of CFC-222 was similar to that of sparfloxacin, but less than that of
      ciprofloxacin. However, it was less active than ciprofloxacin and sparfloxacin
      against Pseudomonas aeruginosa. In mouse systemic infection caused by S. aureus
      Smith or S. aureus TMS 33, CFC-222 demonstrated an activity similar to that of
      ciprofloxacin and sparfloxacin, but better than that of ofloxacin. The compound
      was more effective than ciprofloxacin and sparfloxacin in murine infection caused
      by Streptococcus pyogenes ATCC 8668. Against Escherichia coli, Klebsiella
      pneumoniae and Enterobacter cloacae infections, the efficacy of CFC-222 was
      similar to those of ciprofloxacin, ofloxacin and sparfloxacin. The activity of
      CFC-222 was similar to those of ciprofloxacin and sparfloxacin against P.
      aeruginosa MB4-16 in the same infection model. These results suggest that CFC-222
      may be a promising therapeutic agent for the treatment of various bacterial
      infections.

PMID- 9533465
TI  - The effect of protein binding and lipophilicity of penicillins on their in-vitro
      flux across gastric mucosa.
AB  - Delivery of amoxycillin across the human gastric mucosa to Helicobacter pylori is
      poor compared with that of metronidazole and clarithromycin, limiting the
      clinical effectiveness of this penicillin. To investigate the physicochemical
      properties of penicillins that influence their flux across gastric mucosa, the
      fluxes of metronidazole and eight penicillins were measured in vitro across rat
      gastric mucosa. The lipophilicity of these drugs was also measured using
      potentiometric titration. The mean fluxes of monobasic penicillins (range 0.66
      0.89 nmol/cm2/h) were significantly lower than those of the aminopenicillins
      (range 1.94-2.80 nmol/cm2/h) (P < 0.005). Penicillin flux was not significantly
      correlated with lipophilicity as measured, but was significantly correlated with
      published protein binding data (rs = 0.9048, P < 0.002). Metronidazole flux was
      significantly higher than that of any penicillin at 22.6 (+/-0.9) nmol/cm2/h (P <
      0.001). Therefore, the in-vitro gastric delivery of penicillins can be predicted
      from protein binding which may in turn predict activity against H. pylori in
      vivo.

PMID- 9533466
TI  - Experimental efficacy of combined ceftriaxone and amoxycillin on penicillin
      resistant and broad-spectrum cephalosporin-resistant Streptococcus pneumoniae
      infection.
AB  - The activity of amoxycillin and ceftriaxone, alone and in combination, was tested
      against four strains of penicillin-resistant pneumococci in vitro and in an
      animal model. Three of the strains were also resistant to third-generation
      cephalosporins. Fractional inhibitory concentration indexes for combined
      amoxycillin and ceftriaxone were measured by the Etest method and were considered
      additive (1.2; 1.1; 1.3 and 1.3 for the four strains). Twenty-four hour time-kill
      curves for two strains showed that the combination was additive or synergic for
      concentrations up to the MIC of the single drugs. The efficacy of these
      antibiotics alone and in various combinations against strains 16089 and 11724
      were investigated in vivo using prolonged (48 h) experimental fibrin clot
      infection in rabbits. The bacterial reductions (delta log10 cfu/g) obtained for
      all the antibiotic combinations tested were significantly higher than those of
      the single drug regimens. The in-vivo efficacy of amoxycillin was significantly
      correlated with the time for which its concentration was above the MIC and that
      of ceftriaxone was correlated with its maximal concentration. From these
      findings, we concluded that, at concentrations easily achievable in humans, the
      combination of amoxycillin and ceftriaxone was strongly synergic against
      infection due to penicillin- and cephalosporin-resistant pneumococci.

PMID- 9533467
TI  - Can susceptibility to an antimicrobial be restored by halting its use? The case
      of streptomycin versus Enterobacteriaceae.
AB  - To test the widespread view that resistance disappears in the absence of
      antimicrobial use, we tested streptomycin against 477 Enterobacteriaceae from the
      Royal London Hospital. Twenty per cent proved resistant although streptomycin is
      little used at the hospital and streptomycin resistance in gram-negative bacteria
      is caused by mechanisms that do not compromise the drugs that are used. Up to 70%
      of the observed resistance was associated with cross-resistance to spectinomycin
      and the presence of ant(3")-Ia, an integron-associated gene carried in Tn21-type
      transposons. This genetic organization may have conserved streptomycin resistance
      in the absence of direct selection pressure.

PMID- 9533468
TI  - Effects of cefixime or co-amoxiclav treatment on nasopharyngeal carriage of
      Streptococcus pneumoniae and Haemophilus influenzae in children with acute otitis
      media.
AB  - A multicentre, open-label, randomized study was performed in 501 out-patients
      with acute otitis media, aged 6-36 months, to study the impact of treatment with
      either cefixime suspension 8 mg/kg/day bd or co-amoxiclav suspension 80 mg/kg/day
      tds for 10 days on nasopharyngeal carriage of Streptococcus pneumoniae and
      Haemophilus influenzae. Of 426 patients with nasopharyngeal cultures at entry to
      the trial, end of treatment and at follow-up visit (35 days after inclusion),
      significant changes in carriage of S. pneumoniae were observed. The proportion of
      penicillin-resistant S. pneumoniae was higher in the samples taken at the end of
      treatment and follow-up than in those taken at inclusion, while the total number
      of children with this microorganism was lower. The difference at the end of
      treatment was greater with co-amoxiclav than with cefixime. For H. influenzae the
      resistance rate remained steady while the number of children with this
      microorganism decreased. At follow-up there was no significant difference between
      the two groups in terms of nasopharyngeal positive culture for S. pneumoniae or
      H. influenzae. Despite these differences, successful clinical responses were
      similar at the end of treatment and at follow-up.

PMID- 9533469
TI  - Adult acute upper respiratory tract infections in Sicily: pattern of antibiotic
      drug prescription in primary care.
AB  - We performed an observational study of the antibiotic-prescribing behaviour of
      Sicilian general practitioners (GPs) in managing acute upper respiratory tract
      infections (URTIs). Seventy-six GPs from 25 towns, representing a patient
      population of 96,630, participated in the study between September 1995 and May
      1996. These physicians issued 2038 antibiotic treatment courses for acute upper
      respiratory tract infections: 792 for acute pharyngitis, 531 for acute
      tonsillitis, 304 for acute laryngitis and tracheitis, 268 for suppurative and non
      suppurative acute otitis media, 124 for acute sinusitis and 19 for acute
      rhinitis. Forty-nine different antibiotics were prescribed. The most commonly
      used therapeutic groups were macrolides (38.6%), cephalosporins (27.1%), a
      combination of penicillins with beta-lactamase inhibitors (15.7%) and extended
      spectrum penicillins (13.5%). For each of the above diseases, except rhinitis,
      more than 30 different antibiotics were used. The choice of the route of
      administration appeared to be influenced by the age of the patients and,
      significantly, by a subjective clinical assessment of disease severity rather
      than by any consideration of epidemiological information or evidence from
      clinical trials. The rather marked variation in antibiotic-prescribing pattern
      for URTIs among Sicilian GPs reflects lack of availability or knowledge of any
      local or national guidelines.

PMID- 9533470
TI  - Surgical prophylaxis in Belgian hospitals: estimate of costs and potential
      savings.
AB  - Between 1991 and 1995 the Belgian National Program for Surveillance of Hospital
      Infections (NSIH) collected data on perioperative antibiotic prophylaxis in 72
      acute care hospitals. From the costs of prophylactic antibiotics for six
      categories of surgical procedure and from discharge summaries for hospitalization
      episodes nationwide, annual drug costs were estimated for 73% of Belgian surgical
      activity. Costs of antibiotics used in these surgical activities were estimated
      at 386-410 million Belgian francs (Bf) per year (US$12.1-12.9 million). After
      agreeing recommendations for best practice, the hypothetical costs of 'optimal'
      antimicrobial prophylaxis were calculated for the same selection of surgical
      procedures. It was calculated that savings of at least 194 million Bf (US$6.1
      million) could be made if recommendations were followed closely. Only the costs
      borne by the National Health Insurance Institute for reimbursement of the
      dispensed drugs were considered in this study. Other direct costs, such as those
      related to drug storage, dispensing and administration, were not included.

PMID- 9533471
TI  - Evaluation of the in-vitro activity of the glycopeptide antibiotic LY333328 in
      comparison with vancomycin and teicoplanin.
AB  - The in-vitro activity of a new glycopeptide antibiotic, LY333328, was compared
      with vancomycin and teicoplanin against clinical isolates of Staphylococcus
      aureus, coagulase-negative staphylococci, vancomycin and teicoplanin resistant
      enterococci, and vancomycin sensitive and resistant enterococci. MIC, MBC, and
      time-kill kinetics were determined for each agent. LY333328 displayed similar or
      improved MIC/MBC values in comparison with vancomycin and teicoplanin. Time-kill
      kinetics for LY333328 demonstrated significantly improved bactericidal activity
      against the isolates. These findings suggest that LY333328 has improved in-vitro
      activity over vancomycin and teicoplanin against a range of gram-positive
      organisms.

PMID- 9533472
TI  - Sensitization of Burkholderia cepacia to antibiotics by cationic drugs.
AB  - Chlorpromazine and prochlorperazine have previously been shown to enhance the
      susceptibility of Burkholderia cepacia to aminoglycosides. To screen other non
      antibiotic drugs containing similar amine (-N-CH3) groups, we examined a range of
      such agents that are in current clinical use for the treatment of non-infectious
      diseases, in combination with antibiotics that are ineffective against B.
      cepacia. At a concentration of 0.2 mM, theobromine, theophylline,
      trifluoperazine, fluophenazine and coumarin-152 significantly reduced (by four
      fold) the MICs of gentamicin and ceftazidime. Theobromine and theophylline also
      reduced the MICs of amikacin and azithromycin.

PMID- 9533473
TI  - Synergy of antibiotics against Streptomyces somaliensis isolates in vitro.
AB  - Eight dual antibiotic combinations were used to investigate possible synergic
      effects against different isolates of Streptomyces somaliensis. The antibiotic
      combinations that showed synergic activity against the isolates were, in
      decreasing order, fusidic acid-rifampicin, erythromycin-penicillin, erythromycin
      fusidic acid, rifampicin-sulphamethoxazole, fusidic acid-sulphamethoxazole and
      erythromycin-rifampicin. Sulphamethoxazole-trimethoprim and rifampicin
      trimethoprim combinations were not synergic against any of the S. somaliensis
      isolates tested.

PMID- 9533474
TI  - Levofloxacin selects fluoroquinolone-resistant methicillin-resistant
      Staphylococcus aureus less frequently than ciprofloxacin.
AB  - Seventeen methicillin-resistant Staphylococcus aureus (MRSA) with unique
      genotypes were examined to determine if resistance occurs more frequently with
      ciprofloxacin or levofloxacin. The mean single-step resistance rate to 4 x MIC of
      ciprofloxacin was 1.05 x 10(-5) (range <4.82 x 10[-11] to 5.06 x 10[-5]), and
      that to levofloxacin was 4.03 x 10(-6) (range <3.57 x 10[-13] to 4.10 x 10[-5])
      (P < 0.05). When serially passaged, the mean MICs of ciprofloxacin and
      levofloxacin increased 3.0 +/- 1.5-fold and 1.8 +/- 1.4-fold, respectively (P <
      0.05). Only four strains became resistant to levofloxacin, but eight became
      resistant to ciprofloxacin (P < 0.05). Ciprofloxacin selects resistant MRSA more
      frequently than levofloxacin.

PMID- 9533475
TI  - Activity of azithromycin, clarithromycin, roxithromycin, dirithromycin,
      quinupristin/dalfopristin and erythromycin against Legionella species by
      intracellular susceptibility testing in HL-60 cells.
AB  - We evaluated a human monocyte cell line (HL-60) as a model for testing the
      intracellular activity of anti-Legionella antibiotics; 1.5 x 10(6) HL-60
      cells/well were differentiated into adherent cells and infected with 1.5 x 10(7)
      cfu of Legionella pneumophila. The most active agents against L. pneumophila as
      judged by broth dilution MICs were (in order of activity) azithromycin,
      clarithromycin, roxithromycin, quinupristin/dalfopristin, erythromycin and
      dirithromycin. The most active inhibitors of L. pneumophila intracellular
      multiplication were (in order of activity) azithromycin, erythromycin,
      quinupristin/dalfopristin, roxithromycin, dirithromycin and clarithromycin. All
      the agents were highly active against Legionella micdadei and Legionella
      bozemanii when compared with L. pneumophila.

PMID- 9533476
TI  - In-vitro activities of paromomycin and lasalocid evaluated in combination against
      Cryptosporidium parvum.
AB  - Using a chemiluminescence immunoassay, paromomycin and lasalocid were shown to
      inhibit Cryptosporidium parvum growth in Madin-Darby canine kidney cells in a
      concentration-dependent manner. The median effective concentrations (EC50s) for
      paromomycin and lasalocid were 1184 mg/L and 0.4 mg/L, respectively. Neither drug
      was cytotoxic to host cells at concentrations up to five times their EC50s. Drug
      combination studies were conducted and the resulting data were analysed by the
      median-effect principle and combination index method. Statistically significant
      synergy was observed when combinations of paromomycin and lasalocid were used at
      ratios of 5000:1 and 2500:1. A possible mechanism for synergy is discussed.

PMID- 9533477
TI  - Endothelial cell compatibility of glycopeptide antibiotics for intravenous use.
AB  - The use of human venous endothelial cells for testing antibiotic solutions for
      intravenous compatibility provides a valuable alternative to animal models. In
      order to evaluate the effect of vancomycin and teicoplanin on the viability of
      human umbilical venous endothelial cells, intracellular ATP levels were measured
      by a luciferin-luciferase assay. Prostacyclin (PGI2) and thromboxane A2 (TXA2)
      were determined by direct radioimmunoassay. Vancomycin at concentrations of 5 and
      10 mg/mL reduced the intracellular ATP content by 18.7% and 69.9%, respectively,
      within 60 min. In contrast, cellular energy charge remained significantly higher
      after incubation with teicoplanin at 5 and 10 mg/mL (reduction 8.7% and 15.5%,
      respectively). Neither vancomycin nor teicoplanin at a concentration of 2 mg/mL
      led to significant ATP decline. However, endothelial cells incubated with
      vancomycin resulted in significantly lower release of PGI2 and TXA2 compared with
      teicoplanin. These results show that teicoplanin is more compatible with
      endothelial cells than vancomycin, and that both antibiotics are well tolerated
      if diluted to a final concentration of 2 mg/mL.

PMID- 9533478
TI  - Efficacy of doxycycline and ciprofloxacin against experimental Yersinia pestis
      infection.
AB  - The efficacies of ciprofloxacin and doxycycline prophylaxis and therapy were
      assessed against experimental pneumonic plague infections induced by two strains
      of Yersinia pestis in a mouse model. When exposed to an aerosol of Y. pestis
      strain GB, containing 8.39 x 10(5) +/- 4.17 x 10(4) cfu, the retained dose was
      7.3 x 10(3) +/- 2.3 x 10(3) cfu. When exposed to an aerosol of Y. pestis strain
      CO-92, containing 1.86 x 10(5) +/- 7.4 x 10(3) cfu, the retained dose was 3.4 x
      10(4) +/- 2.6 x 10(3) cfu. Both strains resulted in a respiratory and systemic
      infection closely resembling human pneumonic plague. Ciprofloxacin prophylaxis
      and therapy was successful against both strains for up to 24 h after challenge,
      but not after 48 h. Both doxycycline prophylaxis and therapy regimens were
      ineffective against both strains, although strain CO-92 was more susceptible in
      vitro to doxycycline than strain GB and supra-MIC levels were achieved in the
      serum and lungs of the animal.

PMID- 9533479
TI  - Antibiotic resistance in Pseudomonas aeruginosa: an Italian survey.
AB  - In order to assess the current level of resistance to widely used antipseudomonal
      antibiotics in clinical isolates of Pseudomonas aeruginosa, a national survey was
      undertaken. Fifteen hospitals throughout Italy participated in the study. The
      University of Catania tested the antibiotic susceptibility of 1005 consecutive
      clinically significant P. aeruginosa collected from March to June 1995. Lack of
      susceptibility, according to NCCLS breakpoints, was at the following rates:
      meropenem, 9.1%; imipenem, 19.3%; ceftazidime, 13.4%; carbenicillin, 27.3%;
      piperacillin, 12%; ticarcillin/clavulanic acid, 22.8%; amikacin, 10.6%; and
      ciprofloxacin, 31.9%. About half of the isolates (44.4%) were not susceptible to
      at least one of the antibiotics tested.

PMID- 9533480
TI  - Stability of the MICs of various antibiotics in different clonal populations of
      methicillin-resistant Staphylococcus aureus.

PMID- 9533481
TI  - Comparative in-vitro activities of GD-40 and other beta-lactamase inhibitors
      against TEM-1 and SHV-2 beta-lactamases.

PMID- 9533482
TI  - Is it Ig Nobler for science to suffer the slings & arrows of outrageous foolery?

PMID- 9533483
TI  - 'Life begins' for Baltimore Longitudinal Study of Aging--research group has 40th
      birthday.

PMID- 9533484
TI  - From the Food and Drug Administration.

PMID- 9533485
TI  - From the Centers for Disease Control and Prevention. National, state, and urban
      area vaccination coverage levels among children aged 19-35 months--United States,
      July 1996-June 1997.

PMID- 9533486
TI  - From the Centers for Disease Control and Prevention. Tetanus among injecting-drug
      users--California, 1997.

PMID- 9533487
TI  - Applications of computer-based clinical guidelines.

PMID- 9533488
TI  - Malaria prevention for travelers.

PMID- 9533489
TI  - Malaria prevention for travelers.

PMID- 9533490
TI  - Defending health care: for patients, not profits.

PMID- 9533491
TI  - Defending health care: for patients, not profits.

PMID- 9533492
TI  - Defending health care: for patients, not profits.

PMID- 9533493
TI  - Defending health care: for patients, not profits.

PMID- 9533494
TI  - The challenge to improve quality of care.

PMID- 9533495
TI  - Efficacy of acupuncture.

PMID- 9533496
TI  - Risks and benefits of varicella vaccine.

PMID- 9533497
TI  - Looking a gift horse in the mouth: corporate gifts supporting life sciences
      research.
AB  - CONTEXT: Throughout the last decade a number of studies have been conducted to
      examine academic-industry research relationships. However, to our knowledge, no
      studies to date have empirically examined academic scientists' experience with
      research-related gifts from companies. OBJECTIVE: To examine the frequency,
      importance, and potential implications of research-related gifts from companies
      to academic life scientists. DESIGN: A mailed survey conducted in 1994 and 1995
      of 3394 faculty who conduct life science research at the 50 universities that
      received the most research funding from the National Institutes of Health in
      1993. SETTING: Research-intensive universities. PARTICIPANTS: A total of 2167 of
      the 3394 faculty responded to the survey (response rate, 64%). MAIN OUTCOME
      MEASURES: The percentage of faculty who received a research-related gift from a
      company in the last 3 years, the perceived importance of gifts to respondents'
      research, and what, if anything, the recipient thought the donor(s) expected in
      return for the gift. RESULTS: Forty-three percent of respondents received a
      research-related gift in the last 3 years independent of a grant or contract. The
      most frequently received gifts were biomaterials (24%), discretionary funds
      (15%), research equipment and trips to meetings (11% each), support for students
      (9%), and other research-related gifts (3%). Of those who received a gift, 66%
      reported the gift was important to their research. More than half of the
      recipients reported that donors expected the following in return for the gift:
      acknowledgment in publications (63%), that the gift not be passed on to a third
      party (60%), and that the gift be used only for the agreed-on purposes (59%). A
      total of 32% of recipients reported that the donor wanted prepublication review
      of any articles or reports stemming from the use of the gift, 30% indicated the
      company expected testing of their products, and 19% indicated that a donor
      expected ownership of all patentable results from the research in which a gift
      was used. However, what recipients thought donors expected differed by the type
      of gift received. CONCLUSIONS: Research-related gifts are a common and important
      form of research support for academic life scientists. However, recipients
      frequently think that donors place restrictions and expect returns that may be
      problematic for recipients as well as institutions.

PMID- 9533498
TI  - Calcium channel blockers and the risk of cancer.
AB  - CONTEXT: Recent epidemiologic studies have raised the concern that calcium
      channel blocker use may increase the risk of cancer overall and of several
      specific cancers. OBJECTIVE: To assess whether calcium channel blocker use
      increases the risk of cancer overall and of specific cancers. DESIGN: Case
      control drug surveillance study based on data collected from 1983 to 1996.
      SETTING: Hospitals in Baltimore, Md, New York, NY, and Philadelphia, Pa.
      PATIENTS: A total of 9513 patients aged 40 to 69 years with incident cancer of
      various sites and 6492 controls aged 40 to 69 years admitted for nonmalignant
      conditions. MAIN OUTCOME MEASURES: Incident cancer overall and 23 specific
      cancers. RESULTS: Calcium channel blocker use was unrelated to the risk of cancer
      overall (relative risk [RR], 1.1; 95% confidence interval [CI], 0.9-1.3). Use was
      not significantly associated with increased risks of individual cancers,
      including those previously implicated, except cancer of the kidney (RR, 1.8; 95%
      CI, 1.1 -2.7). Recent use, use for 5 or more years, and use of individual calcium
      channel blocker drugs were also not associated with cancer incidence. Use of beta
      blockers and angiotensin-converting enzyme inhibitors was generally unrelated to
      cancer overall or individual cancers, but both were associated with kidney cancer
      (RR, 1.8; 95% CI, 1.3-2.5; and RR, 1.9; 95% CI, 1.2-3.0, respectively).
      CONCLUSIONS: The present study suggests that the use of calcium channel blockers
      is unrelated to an increase in the overall risk of cancer or of individual
      cancers, except kidney cancer, which has been associated with hypertension or
      drugs to treat hypertension in previous studies.

PMID- 9533499
TI  - A close look at therapeutic touch.
AB  - CONTEXT: Therapeutic Touch (TT) is a widely used nursing practice rooted in
      mysticism but alleged to have a scientific basis. Practitioners of TT claim to
      treat many medical conditions by using their hands to manipulate a "human energy
      field" perceptible above the patient's skin. OBJECTIVE: To investigate whether TT
      practitioners can actually perceive a "human energy field." DESIGN: Twenty-one
      practitioners with TT experience for from 1 to 27 years were tested under blinded
      conditions to determine whether they could correctly identify which of their
      hands was closest to the investigator's hand. Placement of the investigator's
      hand was determined by flipping a coin. Fourteen practitioners were tested 10
      times each, and 7 practitioners were tested 20 times each. MAIN OUTCOME MEASURE:
      Practitioners of TT were asked to state whether the investigator's unseen hand
      hovered above their right hand or their left hand. To show the validity of TT
      theory, the practitioners should have been able to locate the investigator's hand
      100% of the time. A score of 50% would be expected through chance alone. RESULTS:
      Practitioners of TT identified the correct hand in only 123 (44%) of 280 trials,
      which is close to what would be expected for random chance. There was no
      significant correlation between the practitioner's score and length of experience
      (r=0.23). The statistical power of this experiment was sufficient to conclude
      that if TT practitioners could reliably detect a human energy field, the study
      would have demonstrated this. CONCLUSIONS: Twenty-one experienced TT
      practitioners were unable to detect the investigator's "energy field." Their
      failure to substantiate TT's most fundamental claim is unrefuted evidence that
      the claims of TT are groundless and that further professional use is unjustified.

PMID- 9533500
TI  - Factors associated with fatalities and injuries from hot-air balloon crashes.
AB  - CONTEXT: Despite the increased popularity of hot-air balloon flight, data on
      injuries and fatalities associated with hot-air balloon crashes are limited.
      OBJECTIVE: To determine factors associated with injury and death in hot-air
      balloon crashes. DESIGN: Retrospective review of data collected from reports and
      investigations by the Civil Aeronautics Board and the National Transportation
      Safety Board. STUDY SUBJECTS: Individuals involved in US hot-air balloon crashes
      from 1964 to 1995. MAIN OUTCOME MEASURES: Total number of crashes and factors
      associated with fatality or serious injury. RESULTS: From 1964 to 1995, a total
      of 495 hot-air balloon crashes involving 1533 persons were reported and included
      92 fatalities and 384 serious injuries. Pilot error or incapacitation was
      determined subjectively by crash investigators to contribute to 85.1% of the
      crashes. In univariate analysis, collision with the ground was the most
      significant predictor of a fatality or serious injury (P<.001), and power-line
      contact was the most significant predictor of fatality (P<.001). In multiple
      logistic regression, only the type of object struck by a balloon predicted a
      fatal crash or a fatality or serious injury. CONCLUSIONS: Although a number of
      factors likely contribute to increased severity of hot-air balloon crashes, the
      object struck during a crash is most predictive of fatality or serious injury.
      Preventive efforts are needed to decrease future injuries.

PMID- 9533501
TI  - Shopping around for hospital services: a comparison of the United States and
      Canada.
AB  - CONTEXT: Historical comparisons indicate that US hospitals are more expensive
      than Canadian hospitals, but health care system reform might have changed the
      relative costs and timeliness of health care in the 2 countries. OBJECTIVE: To
      estimate the price and convenience of selected hospital services in the United
      States and Canada for patients in 1997 had they paid out-of-pocket. DESIGN: Cross
      sectional telephone survey conducted May 1996 to April 1997. PARTICIPANTS: The 2
      largest acute care general hospitals from every city in the United States and
      Canada with a population greater than 500000. MEASURES: Each hospital was
      telephoned and asked their price and waiting time for 7 services: magnetic
      resonance imaging of the head without gadolinium; a screening mammogram; a 12
      lead electrocardiogram; a prothrombin time measurement; a session of
      hemodialysis; a screening colonoscopy; and a total knee replacement. Waiting
      times were measured in days until earliest appointment and charges were converted
      to American currency. RESULTS: Overall, 48 US and 18 Canadian hospitals were
      surveyed. Median waiting times were significantly shorter in American hospitals
      for 4 services, particularly a magnetic resonance imaging of the head (3 days vs
      150 days; P<.001). Median charges were significantly higher in American hospitals
      for 6 services, particularly for a total knee replacement ($26805 vs $10651;
      P<.001). Individual services showed no association between shorter waiting times
      and higher prices within each country, with the exception of a total knee
      replacement in the United States. CONCLUSION: US hospitals still provide higher
      prices and faster care than Canadian hospitals for patients who pay out-of
      pocket.

PMID- 9533502
TI  - Reduced ratio of male to female births in several industrial countries: a
      sentinel health indicator?
AB  - CONTEXT: The sex ratio of 1.06:1, the ratio of male to female births, has
      declined over the past decades. Recent reports from a number of industrialized
      countries indicate that the proportion of males born has significantly decreased,
      while some male reproductive tract disorders have increased. OBJECTIVES: To
      examine the evidence for declines in the male proportion at birth and suspected
      causes for this decline, and to determine whether altered sex ratio can be
      considered a sentinel health event. DATA SOURCES: Birth records were analyzed
      from national statistical agencies. STUDY SELECTION: Published analyses of trends
      in ratio of males to females at birth and studies of sex determinants evaluating
      epidemiological and endocrinological factors. DATA EXTRACTION: Proportion of
      males born: 1950-1994 in Denmark; 1950-1994 in the Netherlands; 1970-1990 in
      Canada; and 1970-1990 in the United States. DATA SYNTHESIS: Since 1950,
      significant declines in the proportion of males born have been reported in
      Denmark and the Netherlands. Similar declines have been reported for Canada and
      the United States since 1970 and parallel declines also have occurred in Sweden,
      Germany, Norway, and Finland. In Denmark, the proportion of males declined from
      0.515 in 1950 to 0.513 in 1994. In the Netherlands, the proportion of males
      declined from 0.516 in 1950 to 0.513 in 1994. Similar declines in the proportion
      of males born in Canada and the United States are equivalent to a shift from male
      to female births of 8600 and 38000 births, respectively. Known and hypothesized
      risk factors for reduced sex ratio at birth cannot fully account for recent
      trends. CONCLUSION: Patterns of reduced sex ratio need to be carefully assessed
      to determine whether they are occurring more generally, whether temporal or
      spatial variations are evident, and whether they constitute a sentinel health
      event.

PMID- 9533503
TI  - Computerized prescribing: building the electronic infrastructure for better
      medication usage.
AB  - Computerized prescribing in the practice of medicine is a change that is overdue.
      Virtually all prescriptions in the United States are still handwritten. Instead,
      medications should be ordered on a computer interacting with 3 databases: patient
      drug history, scientific drug information and guideline reference, and patient
      specific (weight, laboratory) data. Current problems with prescribing on which
      computerized prescribing could have a positive impact include (1) drug selection;
      (2) patient role in pharmacotherapy risk-benefit decision making; (3) screening
      for interactions (drug-drug, drug-laboratory, drug-disease); (4) linkages between
      laboratory and pharmacy; (5) dosing calculations and scheduling; (6) coordination
      between team members, particularly concerning patient education; (7) monitoring
      and documenting adverse effects; and (8) postmarketing surveillance of therapy
      outcomes. Computerized prescribing is an important component of clinician order
      entry. Development of this tool has been impeded by a number of conceptual,
      implementation, and policy barriers. Overcoming these constraints will require
      clinically and professionally guided vision and leadership.

PMID- 9533504
TI  - The cost of instant access to health care.

PMID- 9533505
TI  - Disclosure policies for gifts from industry to academic faculty.

PMID- 9533506
TI  - Reframing the geriatric patient.

PMID- 9533507
TI  - Ageism in the preclinical years.

PMID- 9533508
TI  - The geriatrics imperative: meeting the need for physicians trained in geriatric
      medicine.

PMID- 9533509
TI  - Psychosocial impact of Alzheimer disease.

PMID- 9533510
TI  - Mathematical models of growth in stature throughout childhood.
AB  - Growth models for predicting child stature are useful to summarize both the
      pattern and timing of growth in individuals and populations. Jolicoeur el al.
      described the JPPS model and compared it with the models of Preece and Baines
      (PB1) and Shohoji and Sasaki (SS). More recently Jolicoeur et al. described the
      JPA2 model, an extension of the JPPS. Here the JPPS model is studied in greater
      depth, and with more subjects, compared to the PB1 model and a modification of
      the SS model (SSC). The JPPS model gives consistently the best fit, although the
      SSC model is also better appreciably than the PB1. It is shown that biological
      parameters can be derived from the model parameters. Both infancy and adult data
      are required for the JPPS model to fit well. In some subjects the JPPS velocity
      curve suggests a mid-growth spurt, but it does not usually indicate a spurt in
      the underlying data. The SSC model is shown to be similar to Karlberg's ICP
      model. Overall the JPPS model provides a good fit to the child stature curve.

PMID- 9533511
TI  - Influence of religion and birthplace on the genetic structure of Northern
      Ireland.
AB  - The effect of geographic and religious subdivision on the genetic structure of
      Northern Ireland was assessed using data on 10 craniofacial measurements
      collected on 755 adult males that were born in five counties and belonged to one
      of three religious affiliations (Catholic, Church of Ireland, Presbyterian).
      Fifteen samples were defined based on birth county and religious affiliation. Two
      way univariate and multivariate analysis of variance shows significant effects of
      birth county and religious affiliation, with somewhat greater subdivision due to
      religion. Distance matrix correlations reveal a small, but significant, effect of
      birth county and religious affiliation on the pattern of genetic distances
      between the 15 samples, with a slightly greater influence of religion. The Church
      of Ireland samples show the greatest differences. perhaps revealing the combined
      influence of differential population origins and religious differences as a
      barrier to gene flow. Overall, religion has a significant, though minor,
      influence on genetic variation in Northern Ireland.

PMID- 9533512
TI  - Influence of nutrition on growth in premature infants: assessment by knemometry.
AB  - Lower leg length measurements in 19 healthy preterm infants were obtained by
      knemometry to assess short term growth. Eight infants received fortified human
      milk and 11 infants commercially available preterm formulas. Two independent
      observers measured lower leg length in each infant daily during the study period,
      weight was measured daily with a neonatal scale. While weight gain showed
      linearity in all infants, lower leg length growth showed mini growth spurts of 5
      +/- 1.7 days, growth periods of 20 +/- 11 days or both types of short term
      growth. The overall weight gain was 35 +/- 5.6 g/day in infants fed human milk
      and 33 +/- 7 g/day in infants fed preterm formula. The overall lower leg length
      growth velocity was 0.51 +/- 0.04 mm/day versus 0.54 +/- 0.09 mm/day,
      respectively. Both groups had comparable weight and length increments. No
      correlation existed between the type of nonlinear lower leg length growth (mini
      growth spurts versus growth periods) and the feedings received by the infants.

PMID- 9533513
TI  - Anthropology of the apoplipoprotein E (apo E) gene: low frequency of apo E4
      allele in Basques and in tribal (Baiga) populations of India.
AB  - The distribution of apolipoprotein E (apo E) polymorphism was examined in 11
      population groups not previously studied for this system. There is a marked
      difference in phenotype and gene frequency between the populations of England and
      Spain. The south European populations of Basques and Spanish non-Basques showed
      greater similarity to the populations of South Asia. The study clearly indicates
      that the distribution of apo E alleles does match with regions showing a high
      mortality rate of coronary heart disease. The data presented also indicate that
      authochthon groups such as Basques in Europe and tribals in India may throw
      better light on the role of apolipoproteins in the regulation of lipid levels in
      disease.

PMID- 9533514
TI  - Physique and echocardiographic dimensions in children, adolescents and young
      adults.
AB  - Relationships between echocardiographic dimensions and the Heath-Carter
      anthropometric somatotype were considered in healthy, non-obese children (8-11
      year olds, n = 143), adolescents (12 15 year olds, n = 216) and young adults (16
      24 years, n = 190). Cardiac dimensions, measured by M-mode echocardiography at
      end-diastole, included left ventricular internal diameter (LVIDd), posterior wall
      thickness (PWTd), and interventricular posterior wall thickness (STd). Left
      ventricular mass (LVM) and left ventricular end-diastolic volume (LVEDV) were
      estimated. Partial correlations between cardiac dimensions and each somatotype
      component were calculated, controlling for age and the other two components. Only
      9 out of 45 correlations in males and 7 of 45 correlations in females were
      significant (p < or = 0.05). LVM, LVEDV, and LVIDd were significantly related to
      somatotype in males, demonstrating significant positive correlations with
      mesomorphy (r = 0.25, 0.29 and 0.29, respectively) and ectomorphy (r = 0.22.
      0.37, and 0.37, respectively), and LVEDV and LVIDd were related to endomorphy (r
      = 0.24 and 0.25, respectively) in 8-11 year old boys. In 8-11 year old females,
      endomorphy was related to STd (r = 0.41) and LVM (r = 0.34), while mesomorphy was
      related to PWTd (r = -0.34) and ectomorphy was related to PWTd (r = -0.36). In 12
      15 year old females, mesomorphy was related to STd (r = 0.26) and in 16-24 year
      old females, endomorphy was related to LVIDd (r = 0.29) and LVEDV (r = 0.32).
      Overall, the correlations between somatotype and cardiac dimensions were low,
      ranging from -0.36 to +0.41, with no clear pattern in either sex. Additionally, a
      backward stepwise regression analysis indicated that body size was more important
      in predicting echocardiographic dimensions than somatotype. Thus, physique, as
      estimated with the Heath-Carter anthropometric somatotype, is not related to
      echocardiographic dimensions in children, youths and young adults.

PMID- 9533515
TI  - Effect of disparities in birth weight on differences in postnatal growth of
      monozygotic and dizygotic twins.
AB  - Influence of intrapair differences in birth weight (IDBW) on the patterns of
      postnatal growth of MZ and DZ twins from middle/late childhood to adolescence
      were studied in 49 MZ, 40 DZ male and 40 MZ, 35 DZ female pairs coming from the
      Wroclaw Longitudinal Twins Study. Intrapair differences in the patterns in
      postnatal growth were expressed in several indices: average differences in
      standardized values (ASD Height, ASD Weight); absolute average differences in
      standardized values (ABSD Height, ABSD Weight); average Euclidean distances
      coefficient (EUCD Height, EUCD Weight); coefficient of shape differences (SHC
      Height, SHC Weight); measure of deviation (MD Height, MD Weight) and correlation
      coefficient for the standardized attained values (CORC Height, CORC Weight).
      Relationships between IDBW and indices were based on the means of Spearman Rank
      Order Correlation. Additionally for 40 MZ, 35 DZ male and 25 MZ, 18 DZ female
      pairs, the relationships between IDBW and intrapair differences in biological
      parameters derived from Preece Baines model 1, describing differences in time
      (DT1), height (DH1), velocity (DV1) at the beginning of the adolescent growth
      spurt, differences in time (DT2), height (DH2), velocity (DV2) at peak height
      velocity and differences in adult height (DAH) were examined. The results showed
      that only in MZ girls did dissimilarity in birth weights significantly impair the
      subsequent growth in stature. Furthermore, the results revealed that birth weight
      influences the parameter describing adult stature in MZ girls. It is concluded
      that the lack of relationship in DZ twins is due to their unique genotype, which
      strongly determines the postnatal growth. Three possible interpretations are
      given as explanations of the results obtained in this study: male excess neonates
      mortality, 'third factor' and programmed of growth in utero.

PMID- 9533516
TI  - Body mass index reference curves for Chinese children.
AB  - The Hong Kong Growth Survey 1993 provided data for the construction of reference
      curves for body mass index (BMI) of Chinese children from birth to 18 years. Data
      on weight and height was obtained from 11797 boys and 12168 girls. The LMS method
      was used to smooth the percentile curves. These curves showed a definite
      physiological rising pattern to a peak at 6 months, then fell to a trough at 6
      years, before another rise towards adulthood. Compared to published reports from
      the US, Britain, France and Sweden, Hong Kong Chinese children, particularly the
      girls, were less obese. In the first 2 years median curves of Hong Kong Chinese
      were similar to those of the Japanese.

PMID- 9533517
TI  - A brief history of the study of human growth dynamics.
AB  - Human growth is non-linear and short term changes in height velocity cannot be
      used to predict future growth. This paper discusses the current knowledge of
      growth dynamics in the context of a historical review of the subject.

PMID- 9533518
TI  - Update on endocrine therapy for breast cancer.
AB  - The choice of endocrine agent for breast cancer depends on the menopausal status
      of the patient, the stage of disease, prognostic factors, and the toxicity
      profile of the agent. Endocrine therapies are typically given sequentially, with
      the least toxic therapy given first. Tamoxifen is considered first-line endocrine
      therapy for all stages of breast cancer. New antiestrogens in development include
      nonsteroidal agents related to tamoxifen and pure steroidal antiestrogens.
      Luteinizing hormone-releasing hormone agonists are an effective form of endocrine
      therapy for premenopausal women with advanced breast cancer, and aromatase
      inhibitors are effective in postmenopausal women. Newer and more selective
      aromatase inhibitors that are p.o. active and have improved side-effect profiles
      have been developed. Recent trials have found these agents to improve survival in
      comparison to the progestins; thus, aromatase inhibitors are replacing progestins
      as second-line therapy for metastatic disease. Current trials are examining the
      potential role of aromatase inhibitors as first-line therapy for metastatic
      disease or as adjuvant therapy for early disease. The antiprogestins and
      antiandrogens studied thus far have had only limited success in breast cancer
      clinical trials.

PMID- 9533519
TI  - Telomerase: a potential marker of bladder transitional cell carcinoma in bladder
      washes.
AB  - Telomerase is an enzyme that immortalizes cells by maintaining a constant
      telomere length. Here, telomerase activity in bladder washes was analyzed and
      compared with the final pathological diagnosis in 23 patients with bladder
      transitional cell carcinoma (TCC). Bladder washes and normal tissues were
      obtained from each patient prior to transurethral resection of bladder tumor.
      Telomerase activity was detected using telomeric repeat amplification protocol
      assay based on PCR. Cytological diagnosis of centrifuged cells from bladder
      washes was made using Papanicolau's stain. Results demonstrated that telomerase
      activity was detected in 95.7% of both cancer tissues and bladder washes. In
      normal tissues, telomerase activity was not detected in 22 of 23 samples.
      Regarding cytological diagnosis, only 69.6% of bladder wash samples had positive
      cytology. Moreover, in five cases of grade 1 TCC, only 20% of the cytological
      specimens were positive for malignancy, whereas 80% showed positive telomerase
      activity. These results demonstrate that telomerase activity is detectable in a
      majority of human bladder cancer tissues and bladder washes obtained from
      patients with TCC. In addition, results of this study suggest that the presence
      of telomerase in bladder washes may be a specific marker of bladder cancer,
      especially in low-grade tumors.

PMID- 9533520
TI  - Presence of multiple incontiguous deleted regions at the long arm of chromosome
      18 in head and neck cancer.
AB  - The 18q chromosomal region is frequently lost in head and neck squamous cell
      carcinomas (HNSCCs). Several candidate tumor suppressor genes have been mapped to
      this chromosomal region, including DCC, DPC4, and MADR2. The latter two genes are
      members of the Smad family, key downstream mediators in the transforming growth
      factor beta signaling pathway, and their alterations could confer resistance to
      transforming growth factor beta and contribute to tumorigenesis. Nevertheless,
      genetic alterations of DCC and DPC4 in HNSCC have not been frequently reported.
      To further investigate the extent and significance of the loss of the 18q
      chromosomal region in HNSCC, we performed detailed mapping at this region in a
      set of 50 primary HNSCCs using 19 highly polymorphic microsatellite markers. We
      detected loss of heterozygosity in 84% of the tumors tested and were able to
      identify three minimal deleted regions encompassing markers D18S467-D18S474 at
      18q12 (4 cM), D18S1099-D18S487 at 18q21.1 (3 cM), and D18S69-41 at 18q21.1-q21.2
      (2 cM). Of these minimal deleted regions, only one harbors a known candidate
      tumor suppressor gene, DCC, which maps telomeric to D18S46. In addition, the role
      of the MADR2 gene in HNSCCs was investigated by examining nine HNSCC cell lines
      for alterations of the gene by reverse transcription-PCR and direct sequencing
      analysis. No mutations or polymorphisms were detected, making this gene an
      unlikely target of the frequent loss at 18q in HNSCC. Our data indicate high
      frequency of loss of heterozygosity at 18q in HNSCC and the presence of at least
      two as yet unidentified tumor suppressor genes in this chromosomal region.
      Additional efforts to identify these putative tumor suppressor genes are
      warranted.

PMID- 9533521
TI  - Pharmacodynamics of topoisomerase I inhibition: Western blot determination of
      topoisomerase I and cleavable complex in patients with upper gastrointestinal
      malignancies treated with topotecan.
AB  - Analogues of camptothecins are specific inhibitors of eukaryotic DNA
      topoisomerase I (topo I) that lead to DNA damage and, eventually, cellular
      cytotoxicity. Camptothecin analogues bind to this target enzyme in the course of
      its normal function and stabilize the DNA-enzyme adduct to form a "cleavable
      complex." Preclinical experiments using Western blot analyses have shown
      cleavable complex formation to be the key intermediate step in topo I inhibition.
      In this series of experiments, it was our goal to convert this laboratory
      technique into a useful clinical assay, allowing measurement of the target enzyme
      and detection of the key intermediate in clinical specimens taken from patients
      being treated with the topo I inhibitor topotecan. Because available antibodies
      were not sufficiently sensitive at the start of this project, we identified a
      highly specific human SCL-70 antibody from a patient with scleroderma, which
      allowed quantitative determination of topo I copy number in HeLa and HT-29 cell
      lines. Additional refinements of the Western blot technique were accomplished to
      improve signal:noise ratio. In surgical tumor specimens, we found the median topo
      I level to be 30.1 x 10(5) copies/cell for gastric adenocarcinomas, compared to
      18.4 x 10(5) copies/cell for normal gastric mucosae in the same samples. For lung
      adenocarcinoma, the median protein level was 21.5 x 10(5) copies/cell, compared
      with the normal tissue counterpart protein level of 12.7 x 10(5) copies/cell. The
      median tumor:normal ratios from paired samples of these tumor types were 1.51 and
      1.84, respectively. As part of a Phase II study evaluating the efficacy of
      topotecan (1.5-2.0 mg/m2 daily for 5 days) in upper gastrointestinal
      malignancies, we obtained tumor and normal mucosa biopsies in 11 patients with
      gastric or esophageal cancer, 30 min after administration on day 4 or 5. Three
      patients with gastric adenocarcinoma had stable disease as their best response,
      with the remainder of patients progressing. Improvement in Western blotting
      methodology allowed the quantitation of topo I levels in these gastric and
      esophageal cancer biopsies, which could be augmented by brief heating to release
      complexed topo I. We were also able to directly visualize high molecular weight
      topo I-containing bands, which were shown to be cleavable complexes by heat
      reversal, with restoration of the topo I Mr 100,000 band. Using this heat
      reversal technique, we determined the presence of cleavable complex in a total of
      7 of 11 patient biopsy samples (5 tumors and 2 normal mucosae). In patients
      treated with topotecan on this dose and schedule, we determined that a median of
      73% of the total tumor topo I was involved in cleavable complex (range, 18.3
      91%). The intensity of the Mr 100,000 topo I band in biopsy specimens of patients
      receiving topotecan represented "free" or noncomplexed topo I. The median copy
      number for the residual, noncomplexed topo I (n = 11) was 7.36 x 10(5)
      copies/cell, significantly less than the median of 30.1 x 10(5) copies/cell for
      random tumor specimens from patients with gastric adenocarcinomas (P < 0.001).
      Pharmacodynamic analysis demonstrated a negative correlation between the
      noncomplexed topo I copy number and topotecan area under the curve (Spearman rank
      test: r(s) = -0.81, P = 0.003). Nonlinear regression analyses of these data were
      best fit with an inhibitory maximum effect model, yielding parameter estimates
      for Emax and EC50 of 29.3 x 10(5) copies/cell (coefficient of variation = 22%)
      and 43.1 ng x h/ml (coefficient of variation = 27%), respectively. Through a
      series of careful modifications and refinements, we have improved the Western
      blot assay for topo I for use in clinical monitoring. We have demonstrated the
      ability to directly visualize cleavable complex in patients being treated with
      topo I inhibitor therapy and have directly quantitated free topo I, as well as
      the key topo I intermediate (cleavable complex), in biopsy specimens obtained
      from pat

PMID- 9533522
TI  - The prognostic role of p53, metallothionein, P-glycoprotein, and MIB-1 in muscle
      invasive urothelial transitional cell carcinoma.
AB  - Tissue from primary tumors was analyzed for 118 patients with urothelial cancer
      who subsequently received cisplatin-based chemotherapy. Immunohistochemical
      staining was performed for nuclear p53 reactivity; for two proposed mediators of
      drug resistance, metallothionein (MT) and P-glycoprotein; and for the cell
      proliferation marker MIB-1. For each marker, immunoreactivity was expressed as a
      percentage of positively staining cells, and overall intensity of staining was
      graded on a scale from 0 to 3. The product of these two measurements was
      calculated to generate a percentage-intensity index. Clinical data were obtained
      independently via retrospective chart review. Chemotherapy regimens containing
      cisplatin (cisplatin, methotrexate, and vinblastine or methotrexate, vinblastine,
      doxorubicin, and cisplatin) were administered for metastatic disease (n = 64),
      for locally advanced disease (n = 45), or as an adjuvant treatment (n = 9). The
      overall response rate was 56% among 99 evaluable patients, and median survival
      was 12.7 months. By univariate analysis, Eastern Cooperative Oncology Group
      performance status (P = 0.0025), tumor grade (P = 0.03), percentage of MT
      staining (P = 0.01), and percentage-intensity index of MT staining (P = 0.04)
      were significant predictors of response to chemotherapy. The first three of these
      were significant in a multivariate model (P = 0.05, 0.04, and 0.04,
      respectively). By subgroup analysis, the percentage of MT staining predicted for
      response in metastatic disease (P = 0.03), but not in locally advanced disease (P
      = 0.28). Only performance status was significantly related to overall survival (P
      = 0.0001, log-rank test) in the whole cohort. Overexpression of MT in the 64
      patients with metastatic disease was associated with a shorter survival (P =
      0.04). Expression of p53, P-glycoprotein, and MIB-1 did not predict for survival.
      In conclusion, overexpression of MT is associated with a poorer outcome from
      chemotherapy, possibly due to cisplatin resistance.

PMID- 9533523
TI  - The overexpression of RHAMM, a hyaluronan-binding protein that regulates ras
      signaling, correlates with overexpression of mitogen-activated protein kinase and
      is a significant parameter in breast cancer progression.
AB  - RHAMM is an oncogene that regulates signaling through ras and controls mitogen
      activated protein kinase [extracellular signal-regulated protein kinase (ERK)]
      expression in embryonic murine fibroblasts. ERK is a dual-specificity kinase that
      controls expression of proteins relevant to tumorigenesis, proliferation, and
      motility. To assess whether RHAMM and ERK are involved in human breast tumor
      progression, we examined RHAMM, ras, and ERK expression in two cohorts of breast
      cancer patients using reverse transcription-PCR and immunocytochemistry. We show
      that overexpression of RHAMM in primary tumors of two patient cohorts was
      significantly prognostic of poor outcome in breast cancer progression.
      Furthermore, RHAMM overexpression occurred within subsets of tumor cells in the
      primary tumor, and this staining pattern was associated with lymph node
      metastases. The metastases exhibited a significantly higher level of staining for
      RHAMM than did the primary tumor. RHAMM expression strongly correlated with
      overexpression of both ras and ERK, although overexpression of either of these
      two signaling molecules was not by itself a prognostic indicator. These results
      identify a new parameter that is involved in lymph node metastasis of primary
      breast cancers and suggest that quantification of RHAMM overexpression may be a
      useful prognostic indicator for breast carcinoma progression.

PMID- 9533524
TI  - Expression of Bcl-X(L), an antiapoptotic member of the Bcl-2 family, in
      esophageal squamous cell carcinoma.
AB  - Bcl-X, a Bcl-2-related protein, is a potent antagonist of apoptosis in its long
      splice variant (Bcl-X(L)). The present study was performed to determine its
      expression in preneoplastic and neoplastic lesions of the esophagus, its
      correlation with other members of the Bcl-2 family, and its impact on the outcome
      of surgically treated esophageal cancer patients. Samples of normal esophageal
      squamous epithelium (n = 10), severe squamous cell dysplasias (n = 19),
      carcinomas in situ (n = 14), invasive squamous cell carcinomas (n = 172), and
      lymph node metastases (n = 21) were immunohistochemically analyzed for Bcl-X(L)
      expression using a polyclonal anti-Bcl-X(L) antibody. The immunostaining was
      evaluated according to a score system (0-12 points) based on the percentage of
      positive tumor cells and the relative immunostaining intensity. Cytoplasmic
      staining for Bcl-X(L) protein was invariably found in all cell layers of the
      normal esophageal squamous epithelium. In contrast, a considerable portion of
      preneoplastic and neoplastic lesions display a decreased Bcl-X(L) expression as
      compared with that in the normal esophageal epithelium. On comparison of the
      amount of Bcl-X(L) expression between the different types of lesions, however, no
      significant differences were found between severe squamous cell dysplasias (mean
      immunoreactive score +/- SD, 5.2 +/- 1.8), carcinomas in situ (5.2 +/- 2.2),
      invasive carcinomas (4.5 +/- 2.8), and lymph node metastases (4.2 +/- 2.6). In
      invasive carcinomas, Bcl-X(L) expression decreased continuously with decreasing
      tumor differentiation (P = 0.0001) and was also directly correlated with bcl-2
      associated X protein expression (P = 0.0001). On the contrary, an inverse
      correlation was found between Bcl-X(L) expression and Bcl-2 protein expression (P
      = 0.0001). No correlation was found between Bcl-X(L) expression and the
      parameters pT category, pN category, and tumor size. In the univariate survival
      analysis, patients with low immunoreactive scores (< or = 4) of Bcl-X(L)
      expression in the tumor tissue showed lower 2-year and 5-year survival rates than
      patients with high immunoreactive scores (> 4; P = 0.0485). In multivariate
      survival analysis, however, only the parameters pN category and pT category, but
      not Bcl-X(L) expression, could be verified as independent prognostic factors.
      This tendency of decreasing levels of an antiapoptotic protein toward unfavorable
      outcome is supported by an increasing number of studies on the role of Bcl-2,
      another antiapoptotic protein, and must be interpreted against the backdrop of
      apoptosis as a result of the interaction of many cell death-promoting and
      protecting proteins.

PMID- 9533525
TI  - Minimal recruitment and activation of dendritic cells within renal cell
      carcinoma.
AB  - Dendritic cells (DCs) are predicted to participate in natural tumor immunity by
      migrating into tumors, where they acquire antigen, undergo activation, and
      migrate to lymph nodes to initiate a T-lymphocyte response against tumor
      associated antigens. The presence of DCs using defined lineage markers and their
      function in human tumors has not been assessed previously. The monoclonal
      antibodies against CMRF-44 and CD83, which are differentiation/activation
      antigens on DCs, were used in immunohistological and flow cytometry studies to
      analyze the DC subtypes infiltrating 14 cases of human renal cell carcinoma
      (RCC). The functional immunocompetence of the DCs isolated from RCC was assessed
      by testing their ability to stimulate an allogeneic mixed leukocyte reaction. The
      majority of leukocytes present within the RCC were macrophages (62% +/- 14.7) or
      T lymphocytes (19% +/- 9.5), with CD45+ HLA-DR+ lineage-negative putative DCs
      accounting for less than 10% of the leukocytes present. Of these, a subset,
      comprising less than 1% of total leukocytes, had an activated CMRF-44+ or CD83+
      DC phenotype. Activated CMRF-44+ and CD83+ DCs were more evident outside the
      tumor in association with T-lymphocyte clusters. The number of CMRF-44+ DCs
      correlated closely with the number of S-100-positive DCs. Isolation of DCs from
      eight RCCs was achieved, and flow cytometry studies confirmed the small
      proportion of activated CMRF-44+ DCs. The CMRF-44+ DCs stimulated an allogeneic
      mixed leukocyte reaction, but the CMRF-44- DCs (normal tissue DC precursors and
      other cells) failed to do so. These results suggest that RCCs recruit few DCs
      into the tumor substance, and the tumor environment fails to initiate the
      expected protective activation of DCs. These two mechanisms, amongst others, may
      contribute to tumor escape from immunosurveillance. In vitro loading of DCs with
      tumor-associated antigens may be a useful therapeutic maneuver.

PMID- 9533526
TI  - Phase I and pharmacokinetic study of GI147211, a water-soluble camptothecin
      analogue, administered for five consecutive days every three weeks.
AB  - GI1147211 is a 7-substituted 10,11-ethylenedioxy-20(S)-camptothecin analogue that
      inhibits the nuclear enzyme topoisomerase I. In this Phase I and pharmacological
      study, 24 patients with advanced solid malignancies received a total of 72
      courses of GI147211 as a 30-min infusion daily for 5 consecutive days, at doses
      ranging from 0.3 to 1.75 mg/m2/day. Severe neutropenia precluded dose escalation
      above 1.5 mg/m2/day in minimally pretreated patients, and both severe neutropenia
      and thrombocytopenia were dose limiting in heavily pretreated patients at doses
      above 1.0 mg/m2/day. These doses are, therefore, recommended for subsequent Phase
      II evaluations of GI147211 in patients with comparable prior therapy.
      Nonhematological toxicities, including nausea, vomiting, fatigue, and anorexia,
      were mild to moderate. The disposition of GI147211 in blood was described by a
      linear three-compartment model, with renal elimination accounting for only 11% of
      drug distribution. No relationship was observed between the pharmacological
      exposure to GI147211 and effects on neutrophils; however, patients who developed
      dose-limiting myelosuppression did experience greater exposure to both the
      lactone and total forms of the drug. The hydrolysis kinetics of GI147211 revealed
      not only a shift of the drug to the inactive carboxylate form in human serum
      albumin but also stabilization of the lactone in erythrocytes, perhaps accounting
      for the observed lactone:total area under the concentration-time curve ratio of
      0.27. These results indicate that GI147211 exhibits predictable toxicities and
      that further studies are warranted to determine the distinct role of this
      compound among currently available camptothecin analogues.

PMID- 9533527
TI  - A phase I and pharmacokinetic study of LY231514, the multitargeted antifolate.
AB  - LY231514 is a novel antifolate that principally inhibits thymidylate synthase,
      but with additional folate-dependent enzyme targets. A Phase I study of single
      agent LY231514 administered as a daily i.v. infusion over 10 minutes for 5 days,
      repeated every 3 weeks, was conducted to evaluate the maximum tolerated dose,
      pharmacokinetic profile, and antitumor activity of the drug using this schedule.
      Thirty-eight patients with advanced malignancies that were refractory or not
      amenable to standard therapy were treated with a total of 116 courses of
      LY231514, escalating treatment doses through 10 dose levels, from 0.2-5.2
      mg/m2/day. No objective clinical responses were observed, although minor
      antitumor activity not fulfilling the response criteria was seen in three
      patients. A maximum tolerated dose of 4.0 mg/m2/day was determined, with
      neutropenia as the predominant dose-limiting toxicity. Reversible disturbances of
      liver biochemistry, fulfilling the protocol definitions of dose-limiting
      toxicity, were also observed. Other toxicities included diarrhea, mucositis, skin
      rash, and fatigue. Pharmacokinetic studies were performed at all treatment
      levels. Analysis showed a linear relation between administered dose and both
      maximum plasma concentration (Cmax) and area under the plasma concentration/time
      curve. The drug was cleared with a day 1 total body clearance of 108.9 +/- 38.8
      ml/min/m2, with plasma concentrations declining with a mean harmonic terminal
      half-life of 1.4 +/- 0.98 h. When given by this schedule, LY231514 is tolerable,
      and Phase II studies are in progress.

PMID- 9533528
TI  - Phase Ib trial of bryostatin 1 in patients with refractory malignancies.
AB  - A Phase Ib trial of bryostatin 1, a macrocyclic lactone and protein kinase C
      (PKC) activator, was conducted in patients with refractory nonhematological
      malignancies with the primary goal of determining whether down-regulation of
      peripheral blood mononuclear cell (PBMNC) PKC activity could be achieved in vivo
      in humans. Patients (four patients/cohort) received bryostatin 1 (25 microg/m2)
      as a 1-h infusion weekly three times every 4 weeks, but to study the schedule
      dependence of pharmacokinetics and pharmacodynamics, the first dose was
      administered according to one of three schedules: (a) a 1-h infusion; (b) a 24-h
      infusion; or (c) a split course (12.5 microg/m2 as a 30-min infusion) on days 1
      and 4. Conventional toxicities (grades I-III) included myalgias, fever, anemia,
      fatigue, phlebitis, and headache; in addition, two patients in cohort 3
      experienced transient elevations in liver function tests, although these patients
      had preexisting liver metastases. No objective clinical responses were
      encountered. Effects on PBMNC PKC activity were heterogeneous. Several patients
      in cohorts 1 and 2 experienced significant declines in activity (approximately
      50%) that were sustained in some cases for periods of > or = 72 h. Comparison of
      72-h with baseline values for all three patient cohorts combined revealed a trend
      toward PKC down-regulation (P = 0.06; signed rank test). For each schedule,
      plasma bryostatin 1 levels were below the level of detection of a platelet
      aggregation-based bioassay (3-4 nm). Bryostatin 1 administration failed to
      produce consistent alterations in lymphocyte immunophenotypic profiles,
      interleukin 2-induced proliferation, or cytotoxicity, although two of three
      samples from patients in cohort 3 did show significant posttreatment increases in
      proliferation. Moreover, in some patients, bryostatin 1 treatment increased
      lymphokine-activated killer cell activity. These findings indicate that
      bryostatin 1 doses of 25 microg/m2 can induce in vivo PBMNC PKC down-regulation
      in at least a subset of patients and raise the possibility that higher bryostatin
      1 doses may be more effective in achieving this effect.

PMID- 9533530
TI  - Phase I study of the orally administered butyrate prodrug, tributyrin, in
      patients with solid tumors.
AB  - Butyrates have been studied as cancer differentiation agents in vitro and as a
      treatment for hemoglobinopathies. Tributyrin, a triglyceride with butyrate
      molecules esterified at the 1, 2, and 3 positions, induces differentiation and/or
      growth inhibition of a number of cell lines in vitro. When given p.o. to rodents,
      tributyrin produces substantial plasma butyrate concentrations. We treated 13
      patients with escalating doses of tributyrin from 50 to 400 mg/kg/day. Doses were
      administered p.o. after an overnight fast, once daily for 3 weeks, followed by a
      1-week rest. Intrapatient dose escalation occurred after two courses without
      toxicity greater than grade 2. The time course of butyrate in plasma was assessed
      on days 1 and 15 and after any dose escalation. Grade 3 toxicities consisted of
      nausea, vomiting, and myalgia. Grades 1 and 2 toxicities included diarrhea,
      headache, abdominal cramping, nausea, anemia, constipation, azotemia,
      lightheadedness, fatigue, rash, alopecia, odor, dysphoria, and clumsiness. There
      was no consistent increase in hemoglobin F with tributyrin treatment. Peak plasma
      butyrate concentrations occurred between 0.25 and 3 h after dose, increased with
      dose, and ranged from 0 to 0.45 mM. Peak concentrations did not increase in three
      patients who had dose escalation. Butyrate pharmacokinetics were not different on
      days 1 and 15. Because peak plasma concentrations near those effective in vitro
      (0.5-1 mM) were achieved, but butyrate disappeared from plasma by 5 h after dose,
      we are now pursuing dose escalation with dosing three times daily, beginning at a
      dose of 450 mg/kg/day.

PMID- 9533529
TI  - Active immunotherapy with ultraviolet B-irradiated autologous whole melanoma
      cells plus DETOX in patients with metastatic melanoma.
AB  - Our objective was to determine the clinical activity, toxicity, and immunological
      effects of active immunotherapy using UVB-irradiated (UVR) autologous tumor (AT)
      cells plus adjuvant DETOX in metastatic melanoma patients. Eligibility included
      nonanergic patients fully recovered after resection of 5 or more grams of
      metastatic melanoma. Treatment consisted of intradermal injections of 10(7) UVR
      AT plus 0.25 ml of DETOX every 2 weeks x 6, then monthly. Peripheral blood
      mononuclear cells (PBMCs) were harvested for cytotoxicity assays, and skin
      testing was performed for delayed-type hypersensitivity (DTH) determinations
      before the first, fourth, seventh, and subsequent treatments. Forty-two patients
      were treated, 18 in the adjuvant setting and 24 with measurable disease. Among
      the latter group, there were two durable responses in soft-tissue sites and in a
      bone metastasis. Treatment was well tolerated. Thirty-five patients were
      assessable for immunological parameters; 10 of these patients, including the 2
      responders, demonstrated early induction of PBMC cytotoxicity against AT cells
      that persisted up to 10 months on treatment before falling to background levels.
      In five of seven patients, the fall-off heralded progressive disease. Late
      induction of a weak DTH reaction to AT cells was observed in eight patients.
      Active immunotherapy with UVR-AT + DETOX had modest but definite clinical
      activity in advanced melanoma. The induction of both PBMC cytotoxicity and DTH
      reactivity to AT cells supported a specific systemic immune effect of treatment,
      although the former more closely followed disease course in this study.

PMID- 9533531
TI  - Phase I/II trial of all-trans retinoic acid and tamoxifen in patients with
      advanced breast cancer.
AB  - Because tamoxifen and all-trans-retinoic acid (ATRA) have additive antitumor
      effects in preclinical systems, we performed a Phase I/II clinical trial of this
      combination in patients with advanced breast cancer. Patients with potentially
      hormone-responsive advanced breast cancer were enrolled. All received 20 mg of
      tamoxifen by mouth daily. Consecutive cohorts of 3-6 patients were treated on odd
      numbered weeks with ATRA at doses of 70, 110, 150, 190, or 230 mg/m2/day. Twenty
      six patients were entered in this trial; 25 were evaluable. A dose of 230 mg/m2
      ATRA produced unacceptable headache and dermatological toxicity, but doses < or =
      190 mg/m2 were tolerable. Two of 7 patients with measurable disease responded.
      Seven of 18 patients with evaluable, nonmeasurable disease achieved disease
      stability for more than 6 months. Plasma AUCs on day 1 of successive weeks of
      treatment were stable over time. A nonsignificant decrease in serum insulin-like
      growth factor I levels was noted during treatment, but this trend was similar to
      that observed in three "control" patients treated with tamoxifen alone. When
      given with daily tamoxifen, the maximum tolerated dose of ATRA that could be
      given on alternate weeks was 190 mg/m2/day. This schedule of ATRA resulted in
      repeated periods of exposure to potentially therapeutic concentrations of ATRA.
      Declines in the serum insulin-like growth factor I concentrations observed in
      patients treated with tamoxifen and ATRA were similar to those observed in
      patients treated with tamoxifen alone. Objective responses were observed, some in
      patients who had previously progressed while receiving tamoxifen, suggesting that
      further studies would be of interest.

PMID- 9533532
TI  - Interferon-gamma and monoclonal antibody 131I-labeled CC49: outcomes in patients
      with androgen-independent prostate cancer.
AB  - To assess the tumor targeting, safety, and efficacy of monoclonal antibody 131I
      labeled CC49 in patients with androgen-independent prostate cancer, 16 patients
      received 75 mCi/m2 of the radiolabeled antibody after 7 days of IFN-gamma
      pretreatment. Sequential tumor biopsies in three patients showed a median 5-fold
      (range, 2-6-fold) increase in the proportion of cells staining positively for the
      TAG-72 antigen, whereas one showed a decrease in staining. Fourteen patients
      received 131I-labeled CC49, whereas 2 showed a disease-related decrease in
      performance status, precluding antibody treatment. The antibody localized to
      sites of metastatic androgen-independent prostate cancer in 86% (12 of 14; 95%
      confidence interval, 57-95%) of cases. Both osseous and extraosseous sites were
      visualized, and in six (42%) patients, more areas were visible when the
      radioimmunoconjugate was used than were apparent when conventional scanning
      techniques were used. The localization of the conjugate in the marrow cavity was
      usually a site not visualized by the radionuclide bone scan, in which the isotope
      localizes primarily to the tumor-bone interface. The dose-limiting toxicity was
      thrombocytopenia because five (36%) patients showed grade IV and seven (50%)
      showed grade III effects. In addition, six (42%) patients, four of whom were
      hospitalized, showed a flare in baseline pain, and four showed a decrease in
      pain. No patient showed a >50% decline in prostate-specific antigen, although
      radionuclide bone scans remained stable in four cases for a median of 4 months.
      The results are consistent with dosimetry estimates showing that the delivered
      dose to tumor was subtherapeutic and suggest that approaches that exclusively
      target the bone tumor interface or the marrow stroma may be unable to completely
      eradicate disease in the marrow cavity. For CC49, improving outcomes would
      require repetitive dosing, which was precluded by the rapid development of a
      human antimouse antibody response.

PMID- 9533533
TI  - Pharmacokinetics of cladribine in plasma and its 5'-monophosphate and 5'
      triphosphate in leukemic cells of patients with chronic lymphocytic leukemia.
AB  - The pharmacokinetic parameters of cladribine (CdA) in patient plasma and its
      intracellular nucleotides CdA 5'-monophosphate (CdAMP) and CdA 5'-triphosphate
      (CdATP) were delineated in circulating leukemia cells in 17 patients with chronic
      lymphocytic leukemia, after the last dose intake and up to 72 h thereafter.
      Patients were treated with 10 mg/m2 CdA p.o. on 3 consecutive days. A novel and
      specific ion-pair liquid chromatographic method, which separates the
      intracellular CdA nucleotides, was used. The area under the concentration versus
      time curve (AUC) of CdAMP in leukemia cells was generally higher (median, 47
      micromol/liter x h) than the AUC of CdATP (median, 22 micromol/liter x h);
      however, in some patients (3 of 17), the reverse relationship was seen. The
      median ratio between the AUC values for CdATP and CdAMP was 0.60 (95% confidence
      interval, 0.4-1.0). The median half-life (t(1/2)) of CdAMP was 15 h, and that of
      CdATP was 10 h. The median terminal t(1/2) of CdA in plasma was 21 h. A
      significant correlation was found between the maximum plasma CdA and cellular
      CdAMP concentrations (r = 0.56, P = 0.02). There was no correlation between the
      AUC values of cellular CdAMP and CdATP (r = 0.224, P = 0.55). No correlation was
      found between deoxycytidine kinase activity and intracellular pharmacokinetic
      parameters of CdAMP or CdATP. The response to treatment was not significantly
      related to intracellular concentration of CdAMP or active metabolite CdATP. There
      is great heterogeneity among patients in terms of AUC and t(1/2) of CdAMP and
      CdATP. Furthermore, the results emphasize the differences between the
      pharmacokinetics of plasma CdA and those of the metabolites in circulating
      leukemic cells.

PMID- 9533534
TI  - Significance of circulating hepatocyte growth factor level as a prognostic
      indicator in primary breast cancer.
AB  - The circulating hepatocyte growth factor (HGF)/scatter factor level is frequently
      increased in advanced cancer patients. In this study, we have assessed the
      prognostic value of the circulating HGF level determined by enzymatic immunoassay
      in primary breast cancer patients. Of 200 primary breast cancer patients, 54
      (27.0%) showed the increase of serum HGF level according to the age-matched
      cutoff values. The prognosis of the patients with the increased HGF level was
      statistically worse than that of the patients with normal HGF level (P = 0.0001,
      log-rank test). Multivariate analysis confirmed that the increase in HGF level
      was an independent prognostic indicator in primary breast cancer patients. In the
      background analysis, the increase in serum HGF level was significantly associated
      with tumor size, nodal status, and histological evidence of venous invasion. The
      data indicate that up-regulation of the circulating HGF level may predict
      systemic tumor spread and early relapse in primary breast cancer patients.

PMID- 9533535
TI  - Epstein-Barr viral DNA in serum of patients with nasopharyngeal carcinoma.
AB  - This study evaluated Epstein-Barr virus (EBV) DNA in sera of 42 patients with
      nasopharyngeal carcinoma (NPC) and 82 healthy individuals who had been infected
      previously with EBV. Thirteen of 42 NPC samples were positive for EBV DNA in
      their sera, whereas all 82 normal controls were negative. In addition, EBV typing
      between primary tumors and sera showed identical results, suggesting that serum
      EBV DNA represented tumor DNA. To evaluate the importance of the serum NPC DNA,
      clinical data and tumor phenotypes including age, sex, WHO type, EBV type, stage,
      tumor invasion, metastasis, and apoptosis were correlated with serum EBV DNA, and
      only apoptosis was found statistically significant. In conclusion, EBV DNA was
      detectable in the serum of some patients with NPC, represented tumor DNA, and
      might have clinical implications in the future.

PMID- 9533536
TI  - Prognostic value of chorionic gonadotropin beta gene transcripts in human breast
      carcinoma.
AB  - The beta subunit of human chorionic gonadotropin is potentially encoded by six
      genes, which can be categorized into two types based on a sequence change at
      codon 117: GCC for the type I and GAC for the type II genes. We previously showed
      that, whereas type I genes were exclusively expressed in normal breast tissues,
      expression of type II genes was associated with malignant transformation (Bellet,
      D., et al. Cancer Res., 57: 516-523, 1997). We designed a simple and robust test
      (the CG117 assay) that measures the percentage of type II over both types of
      chorionic gonadotropin beta mRNAs. Normal breast tissues consistently had a
      negative CG117 index, whereas cancer breast tissues showed indexes ranging from 0
      to 100%. The prognostic significance of the CG117 index was investigated in a
      series of 99 unilateral invasive primary breast cancer patients with known long
      term outcome (median follow-up, 9 years). The CG117 index was positive in 48
      (48.5%) of the 99 tumor mRNA samples. The index was not significantly associated
      with standard prognostic parameters, including clinical and macroscopic tumor
      size, histopathological grade, and lymph node status or steroid receptor status.
      Patients with a positive CG117 index in primary tumor mRNA had significantly
      shorter metastasis-free survival (P = 0.014) and overall survival (P = 0.038)
      after surgery, compared to patients with a negative index. The prognostic
      significance of the CG117 index persisted in Cox multivariate regression
      analysis, both for metastasis-free survival (P = 0.008) and overall survival (P =
      0.016), together with lymph node status (P = 0.027 and P = 0.009, respectively).
      These findings indicate that the CG117 index may contribute to the identification
      of high-risk breast cancer patients.

PMID- 9533537
TI  - Proliferative activity and micronucleus frequency after radiation of lung cancer
      cells as assessed by the cytokinesis-block method and their relationship to
      clinical outcome.
AB  - We previously proposed a new assay using the cytokinesis-block micronucleus (MN)
      technique to estimate the fraction of cells undergoing mitosis in vitro [dividing
      fraction (DF)], potential doubling time (Tpot), and radiosensitivity (in terms of
      MN frequency) of human tumors. In the present study, we applied this technique to
      primary lung cancers to evaluate their biological characteristics, and the assay
      results for the proliferative activity were compared with the treatment outcome.
      Tumor tissues were disaggregated to single cells, which were cultured in the
      presence of cytochalasin B after (or without) radiation. At intervals, the
      proportion of multinucleate cells (its maximum value is the DF), the average
      number of nuclei/cell, and MNs in binucleate cells were scored. The Tpot was the
      extrapolated time for the nuclei:cell ratio to reach 2.0. Of the 71 tumor samples
      obtained, the DF and Tpot were evaluable in 61 (86%), and the MN frequency was
      evaluable in 52 (73%). The median DF and Tpot values were 23% and 7.7 days,
      respectively, for adenocarcinoma (n = 41), 26% and 8.9 days for squamous cell
      carcinoma (n = 13), 27% and 6.5 days for large cell carcinoma (n = 3), and 30%
      and 7.0 days for small cell carcinoma (n = 4). There was no significant
      difference in the mean DF or Tpot values according to the histological type or
      disease stage. The mean MN frequency after 2 Gy of radiation (minus the 0 Gy
      frequency) was 0.15 for adenocarcinoma, 0.17 for squamous cell carcinoma, 0.16
      for large cell carcinoma, and 0.20 for small cell carcinoma. The MN frequency
      after radiation was positively correlated with both the DF and the baseline (at 0
      Gy) MN frequency. In non-small cell lung cancer, a DF above the median was
      associated with an increased recurrence rate after operation, and the Tpot was
      correlated with the time until relapse in patients who developed recurrence.
      Although the clinical significance of the MN frequency needs to be clarified in
      future studies, the DF and Tpot determined by this assay appear to be good
      parameters of tumor proliferative activity.

PMID- 9533538
TI  - Effect of pyrazoloacridine (NSC 366140) on DNA topoisomerases I and II.
AB  - Pyrazoloacridine (PA), an acridine congener with an unknown mechanism of action,
      has shown selective activity against solid tumor cells, cytotoxicity in
      noncycling and hypoxic cells, and promising antitumor activity in Phase I
      clinical trials. In the present study, the effect of PA on topoisomerase (topo)
      activity was evaluated using yeast strains lacking functional topo I or II,
      mammalian cell nuclear extracts, purified samples of mammalian topo I and topo
      II, and intact mammalian tissue culture cells. Clonogenic assays revealed that PA
      cytotoxicity in yeast strains was unaffected by selective loss of topo I or topo
      II activity. On the other hand, enzyme assays revealed that 2-4 microM PA
      abolished the catalytic activity of both topo I and topo II in vitro. In contrast
      to topotecan and etoposide, PA did not stabilize covalent topo-DNA complexes.
      Instead, PA inhibited topotecan-induced stabilization of covalent topo I-DNA
      complexes and etoposide-induced stabilization of topo II-DNA complexes in vitro
      and in intact cells. Consistent with these results, colony-forming assays
      indicated that short-term PA exposure inhibited the cytotoxicity of topotecan and
      etoposide, whereas prolonged PA exposure was itself toxic to these cells.
      Accumulation studies revealed that PA was concentrated as much as 250-fold in
      drug-treated cells, resulting in intranuclear concentrations that far exceeded
      those required to inhibit topo I and topo II. Collectively, these results not
      only suggest that PA can target both topo I and topo II at clinically achievable
      concentrations but also indicate that its mechanism is distinct from topo I and
      topo II poisons presently licensed for clinical use.

PMID- 9533539
TI  - Inhibition of cell growth and telomerase activity of breast cancer cells in vitro
      by 3'-azido-3'-deoxythymidine.
AB  - The effect of zidovudine (3'-azido-3'-deoxythymidine; AZT) was investigated in
      four breast cancer cell lines, a T4 cell leukemia, and a normal breast cell line
      in vitro. AZT inhibited the growth of all tumoral cell lines, but it did so in a
      wide range of concentrations. The growth of a normal breast cell line was also
      inhibited, although it required a much higher concentration. Furthermore, AZT
      inhibited colony formation in soft agar and telomerase activity. These results
      indicated that AZT can be potentially used, alone or in combination, as an anti
      breast cancer agent.

PMID- 9533540
TI  - Tamoxifen-resistant fibroblast growth factor-transfected MCF-7 cells are cross
      resistant in vivo to the antiestrogen ICI 182,780 and two aromatase inhibitors.
AB  - Although the antiestrogen tamoxifen has been the mainstay of therapy for estrogen
      receptor (ER)-positive breast cancer, successful treatment of responsive tumors
      is often followed by the acquisition of tamoxifen resistance. Subsequently, only
      30-40% of patients have a positive response to second hormonal therapies. This
      lack of response might be explained by mechanisms for tamoxifen resistance that
      sensitize ER pathways to small amounts of estrogenic activity present in
      tamoxifen or that bypass ER pathways completely. To elucidate one possible
      mechanism of tamoxifen resistance, we treated ovariectomized tumor-bearing mice
      injected with fibroblast growth factor (FGF)-transfected MCF-7 breast carcinoma
      cells with the steroidal antiestrogen ICI 182,780 or one of two aromatase
      inhibitors, 4-OHA or letrozole. These treatments did not slow estrogen
      independent growth or prevent metastasis of tumors produced by FGF-transfected
      MCF-7 cells in ovariectomized nude mice. FGF-transfected cells had diminished
      responses to ICI 182,780 in vitro, suggesting that autocrine activity of the
      transfected FGF may be replacing estrogen as a mitogenic stimulus for tumor
      growth. ER levels in FGF transfectants were not down-regulated, and basal levels
      of transcripts for estrogen-induced genes or of ER-mediated transcription of
      estrogen response element (ERE) luciferase reporter constructs in the FGF
      expressing cells were not higher than parental cells, implying that altered
      hormonal responses are not due to down-regulation of ER or to FGF-mediated
      activation of ER. These studies indicate that estrogen independence may be
      achieved through FGF signaling pathways independent of ER pathways. If so,
      therapies directed at the operative mechanism might produce a therapeutic
      response or allow a response to a second course of antiestrogen treatment.

PMID- 9533541
TI  - Efficient generation of autologous peripheral blood-derived cytotoxic T
      lymphocytes against poorly immunogenic human tumors using recombinant CD80
      adenovirus together with interleukin 12 and interleukin 2.
AB  - To generate CTLs against poorly immunogenic human tumor cells, we transfected the
      human CD80 gene into the tumor cells using a replication-deficient adenovirus
      (Ad) vector. The successful surface expression of CD80 was obtained in both
      cultured tumor cell lines and primary cultured tumor cells. Transduction of CD80
      alone was not sufficient to induce cytotoxicity of peripheral blood lymphocytes
      against allogeneic tumor cell lines except for melanoma cells. We, therefore,
      investigated a combined effect of CD80-Ad-infected tumor cells and interleukin 12
      (IL-12). Although 7-day cultivation of autologous or allogeneic lymphocytes with
      CD80-Ad-infected tumor cells and IL-12 slightly enhanced cytotoxicity against
      some allogeneic tumor cells, no substantial cytotoxicity was observed against
      autologous tumor cells. When we extended the culture period to 14 days in the
      presence of IL-2, a prominent enhancement of cytotoxicity was observed against
      both allogeneic and autologous tumor cells. Cytotoxicity against autologous tumor
      cells, but not against allogeneic tumor cells, was efficiently inhibited by anti
      CD3 monoclonal antibody. Furthermore, the selective cytotoxicity against a panel
      of targets indicated that the induced CTLs recognize specific antigens on
      autologous tumor cells. These results suggest that stimulation with a combination
      of IL-12- and CD80-modified tumor cells and subsequent expansion with IL-2 may
      efficiently generate tumor-specific CTLs from autologous peripheral blood
      lymphocytes. Our data imply that the combination of CD80 transduction and
      suitable cytokines is useful for enhancing antitumor immunity to poorly
      immunogenic human tumors.

PMID- 9533542
TI  - Bispecific antibodies increase T-cell stimulatory capacity in vitro of human
      autologous virus-modified tumor vaccine.
AB  - The production and functional testing of two new bispecific (bs) hybrid
      antibodies [Abs; bs Ab hemagglutinin-neuraminidase (HN) x CD3 and bs Ab HN x
      CD28] designed for cancer vaccine modification are described. They allow distinct
      modifications of the human tumor cell vaccine ATV-NDV, an autologous tumor cell
      vaccine already modified by infection with Newcastle disease virus. The bs Abs
      use the viral HN molecule as a common foreign anchoring molecule for attachment
      to the tumor cells and allow the introduction of anti-CD3 or anti-CD28 T-cell
      stimulatory molecules. The bs Abs attached to tumor target cells were able to
      cross-link CTL effector cells and up-regulate T-cell activation markers on
      autologous cancer patient-derived CD4 and CD8 T lymphocytes. This strategy of
      combining a cellular vaccine with a bs Ab is highly specific, quick, and
      economical and has broad-range applications. Five ng or less of target cell-bound
      bs Ab HN x CD28 were effective at augmenting T-cell-mediated antitumor
      cytotoxicity.

PMID- 9533543
TI  - Mechanisms for ganciclovir resistance in gastrointestinal tumor cells transduced
      with a retroviral vector containing the herpes simplex virus thymidine kinase
      gene.
AB  - Transfer of the herpes simplex thymidine kinase (HSV-TK) gene into tumor cells
      confers sensitivity to the cells to the viral drug ganciclovir (GCV). Although
      the efficacy of the HSV-TK/GCV approach is well studied, the mechanisms for the
      resistance of HSV-TK-transduced tumor cells to GCV are poorly understood. Here,
      we examined the mechanisms for GCV resistance in HSV-TK-transduced
      gastrointestinal (GI) cell lines. Our results show that GCV sensitivities vary in
      vitro and in vivo among the different HSV-TK-transduced GI tumor cell lines. GCV
      resistant colonies were isolated from several different HSV-TK-transduced GI
      tumor cell lines after 14 days of GCV treatment. Characterization of GCV
      resistant colonies demonstrated that the HSV-TK gene was either partially or
      completely deleted from the resistant HSV-TK-transduced cells. In the HT-29 RM
      and MIAPACA-2 RM cells, a 220-bp deletion of the gene was found, whereas in the
      HT-29 R1-R5-resistant cells, the whole TK gene was found to be absent.
      Immunocytochemical studies using a polyclonal antibody to the TK protein
      demonstrated that the HSV-TK protein was absent in the GCV-resistant, HSV-TK
      transduced cells. Transfection of the resistant cells with an adenoviral vector
      containing a HSV-TK gene restored sensitivity to GCV. The presence of GCV
      resistant cells was only demonstrable in GI tumor cell lines that also
      demonstrated a poor bystander effect. Our results suggest that GCV resistance
      found in tumor cells transduced with a retroviral HSV-TK gene is due to the lack
      of a functional TK protein in the tumor cells rather than any intrinsic
      resistance of the cells to GCV. In tumor cells with a good bystander effect, the
      small percentage of TK-transduced cells that do not express the TK protein are
      probably killed by the bystander effect because GCV-resistant tumor cells were
      not found in these cell lines. GCV-resistant tumor cells were found only in tumor
      cell lines with a poor bystander effect, by which, presumably, the transduced
      tumor cells lacking a functional TK gene were not killed by the bystander killing
      effect.

PMID- 9533544
TI  - Studies of the efficacy and pharmacology of irinotecan against human colon tumor
      xenograft models.
AB  - Irinotecan, administered i.v. on days 1-5 and 8-12 [(dx5)2 i.v.] has demonstrated
      significant activity against advanced human tumor xenografts. To explore the
      feasibility of prolonged oral administration of irinotecan, we compared the
      efficacy of oral and i.v. irinotecan on the (dx5)2 schedule. We also evaluated
      oral therapy for 12 consecutive weeks [(dx5)12] at 25 and 50 mg/kg and two
      consecutive 5-day courses repeated every 21 days for up to four cycles
      ([(dx5)2]4) at 50 and 75 mg/kg/dose in a series of human colon carcinoma
      xenograft lines. In addition, we evaluated the effect of a sensitive (HC1) and
      resistant (ELC2) human colon adenocarcinoma xenograft on irinotecan and SN-38
      lactone disposition after administration of irinotecan 10 mg/kg i.v. and 10 and
      25 mg/kg p.o. Irinotecan i.v. at 40 mg/kg and oral at 50 and 75 mg/kg on the
      (dx5)2 schedule had similar activity against the panel of adult colon
      adenocarcinoma xenografts. Irinotecan given p.o. also demonstrated significant
      activity against a topotecan-resistant derivative, VRC5/TOPO. Oral administration
      of 75 mg/kg [(dx5)2]4 and 50 mg/kg (dx5)12 achieved complete response in five of
      seven xenograft lines evaluated. After i.v. administration, mice bearing HC1
      xenografts had 43% greater SN-38 lactone systemic exposure compared to those with
      ELC2 xenografts and non-tumor-bearing mice. After oral (10 mg/kg) administration,
      there was a 5-fold higher molar formation of SN-38 lactone compared to i.v. (10
      mg/kg) administration in tumor and non-tumor-bearing mice. SN-38 systemic
      exposure associated with the lowest oral dose (25 mg/kg) achieving complete
      response for HC1 was 942.6 ng/ml x h. These results emphasize the importance of
      pharmacokinetic studies as part of tumor response studies in xenograft models.

PMID- 9533545
TI  - Synergistic effects of 8-chlorocyclic-AMP and retinoic acid on induction of
      apoptosis in Ewing's sarcoma CHP-100 cells.
AB  - The enhanced expression of the regulatory subunit of cyclic AMP (cAMP)-dependent
      protein kinase type I, RIalpha, has been correlated with cancer cell growth.
      Retinoic acid (RA) has been shown to play an important role in the regulation of
      proliferation and differentiation in neoplastic cells. In the present study, the
      effects of cAMP analogue 8-chlorocyclic-AMP (8-Cl-cAMP) and RA (both singly and
      combined) on growth inhibition and apoptosis in Ewing's sarcoma CHP-100 cells
      were evaluated. The inhibitory effects of 8-Cl-cAMP and RA (9-cis-RA, 13-cis-RA,
      and all-trans-RA) on cell viability were time and dose related. The degree of
      growth inhibition induced by 9-cis-RA was the greatest among all of the RA
      analogues (13-cis-RA and all-trans-RA) examined. The combined effects of 8-Cl
      cAMP and RA on the induction of growth arrest at the G0-G1 stage of the cell
      cycle, apoptosis, down-regulation of RIalpha, and cleavage of poly(ADP-ribose)
      polymerase were synergistic. In conclusion, it is clear that RA and 8-Cl-cAMP act
      in a synergistic fashion and have potential for combination chemotherapy for the
      treatment of malignant disease.

PMID- 9533546
TI  - Combined antitumor effect of radiation and ibuprofen in human prostate carcinoma
      cells.
AB  - Recent clinical observations indicate that ibuprofen may alleviate the radiation
      induced dysuria that almost invariably occurs during radiation therapy for
      prostate cancer. Because the use of ibuprofen could consequently become common
      during radiation therapy for prostate cancer, we have been interested in the
      potential interactions between ibuprofen and ionizing radiation on prostate tumor
      cells. The effects of gamma-irradiation and/or ibuprofen on PC3 and DU-145 human
      prostate carcinoma cells were evaluated in vitro using three model systems.
      Clonogenic survival was determined by plating cells 24 h after treatment of
      nearly confluent monolayers. Analysis of cell growth, cell detachment, and
      apoptotic cell death was carried out over a period of up to 9 days after
      treatment of PC3 and DU-145 monolayers. The effect of ibuprofen and/or radiation
      was also probed by observing the inhibition of growth of established PC3 and DU
      145 colonies that were treated on the 14th day of colony growth. Ibuprofen
      enhanced the radiation response of prostate cancer cells in all three in vitro
      models. Both the cytotoxic and radiosensitizing effects of ibuprofen seem to
      require concentrations that are higher than those reported to inhibit
      prostaglandin synthesis, suggesting that other molecular mechanisms may be
      responsible for ibuprofen cytotoxicity.

PMID- 9533547
TI  - Chemosensitization of glioblastoma cells to bis-dichloroethyl-nitrosourea with
      tyrphostin AG17.
AB  - Recent data have suggested that mitochondria play a supportive role in
      maintaining the tumorigenic phenotype. Indeed, antimitochondrial agents have been
      hypothesized to be potential chemosensitizers to human malignancy. We assessed
      the utility of this approach by characterizing the antimitochondrial activity of
      3,5-di-tert-butyl-4-hydroxybenzylidene-malononitrile (AG17), in combination with
      1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) in two human glioblastoma cell lines.
      AG17 (NSC 242557) is a tyrphostin that has been thought to have some
      antimitochondrial activity, with limited tyrosine kinase antagonism, and was used
      at noncytotoxic and nongrowth-inhibitory concentrations (0.25 microM).
      Glioblastoma cells were incubated in AG17, and changes in mitochondrial activity
      were determined. Tumor cells became auxotrophically dependent on uridine and
      pyruvate, indicating the lack of a functioning respiratory chain. Despite this,
      cells continued to exhibit no growth-inhibitory effects. Exposure to AG17 was
      associated with significant depolarization of the mitochondrial membrane
      potential and decreases in mitochondrial mass in both glioblastoma cell lines,
      correlating with the finding of auxotrophic dependence. In contrast, normal human
      astrocytes treated with the same dose of AG17 did not show changes in growth,
      mitochondrial membrane potential, or mass. Indeed, auxotrophic dependence on
      uridine and pyruvate could not be established in these cells. Glioblastoma cells
      became significantly more responsive to BCNU chemotherapy with AG17 pretreatment;
      a linear relationship was noted that correlated the number as well as percentage
      of polarized mitochondria with glioblastoma cell survival at the highest dose of
      BCNU used (144 microg/ml). Normal human astrocytes did not change with regard to
      the dose response to BCNU with previous incubation with AG17. No difference was
      found in the type of cellular death (apoptosis) in either of the glioblastoma
      cell lines, with BCNU treatment alone, or with the combination AG17 and BCNU,
      despite the decrease in polarized mitochondria and mitochondrial mass. AG17 has
      antimitochondrial properties when used at low dose in human glioblastoma, which
      are relatively specific to tumor cells when compared with normal astrocytes. The
      use of AG17 as a chemosensitizer, with drugs such as BCNU, offers a new and
      possibly effective approach to be developed in patients with glial tumors.

PMID- 9533548
TI  - Phenytoin alters the disposition of topotecan and N-desmethyl topotecan in a
      patient with medulloblastoma.
AB  - Topotecan undergoes both renal and hepatic elimination, with topotecan urinary
      recovery ranging from 60 to 70%. We evaluated the potential of phenytoin to alter
      the disposition of topotecan and its N-desmethyl metabolite. A 5-year-old child
      with high-risk medulloblastoma received the first course of topotecan with
      phenytoin and the second course without phenytoin. For both courses, topotecan
      doses were adjusted to achieve a target topotecan lactone plasma area under the
      curve (AUC). Serial plasma samples were obtained, and lactone and total plasma
      concentrations of topotecan, as well as total plasma and cerebrospinal fluid
      concentrations of N-desmethyl topotecan, were measured by high-performance liquid
      chromatography. Phenytoin coadministration increased lactone and total topotecan
      clearance from 43.4 +/- 1.9 L/h/m2 to 62.9 +/- 6.4 L/h/m2, and 20.8 +/- 2.8
      L/h/m2 to 30.6 +/- 4.1 L/h/m2, respectively (P < 0.05). Concomitant phenytoin
      increased the plasma AUC of total N-desmethyl topotecan from 7.5 +/- 0.68 ng/ml x
      h to 16.3 +/- 0.53 ng/ml x h (P < 0.05) at plasma AUC of total topotecan of 226.0
      +/- 5.5 ng/ml x h and 240.9 +/- 39.8 ng/ml x h, respectively. N-Desmethyl
      topotecan penetrated into the cerebrospinal fluid (0.12 +/- 0.01). The patient
      experienced no grade 3 or 4 toxicity. These are the first data documenting
      altered topotecan and N-desmethyl topotecan disposition when coadministered with
      phenytoin and suggests that topotecan may undergo further hepatic metabolism.
      Although there is an increase in exposure to the active N-desmethyl topotecan
      metabolite, it is less than the decrease in exposure to topotecan lactone.
      Therefore, patients concomitantly administered phenytoin may require an increase
      in topotecan dose to achieve a similar pharmacological effect as a patient not
      receiving phenytoin.

PMID- 9533549
TI  - Overexpression of Lerk-5/Eplg5 messenger RNA: a novel marker for increased
      tumorigenicity and metastatic potential in human malignant melanomas.
AB  - The Lerks, ligands of eph-related receptor tyrosine kinases, are a rapidly
      expanding family of genes thought to play an important role in the development
      and oncogenesis of various tissues. However, very little experimental evidence
      supports this hypothesis. Using RNA fingerprinting, we detected increased
      expression of Lerk-5 mRNA in human melanocytes as a response to the tumor
      promoting drug 12-O-tetradecanoylphorbol-13-acetate, which suggests a possible
      role of the Lerks in melanoma tumorigenesis and progression. Therefore, we
      studied Lerk-5 mRNA expression in various melanoma cell lines and tissues of
      melanocytic tumors by semiquantitative reverse transcription-PCR. Modest
      expression of Lerk-5 mRNA was found in two melanoma cell lines derived from early
      primary tumors (WM35 and WM1645B); two metastatic cell lines tested showed a 3.9
      fold increased transcript abundance when compared to the primary cell lines (RPMI
      7951 and SK-Mel5). Progeny of a melanoma cell line with very low Lerk-5 mRNA
      abundance (WM35) showed a 5-fold increase in Lerk-5 mRNA expression when it was
      selected for higher tumorigenicity and multicytokine resistance by passaging in
      nude mice or repeated high-dose UVB irradiation. Consistent with these
      experimental data, we found high levels of Lerk-5 mRNA expression in advanced
      primary malignant melanomas and metastases (n = 22) but significantly lower or
      undetectable mRNA expression in benign melanocytic nevi (n = 9; P < 0.001). We
      conclude that increased Lerk-5 expression possibly reflects or induces an
      increased potential of growth, tumorigenicity, and metastatic abilities in human
      melanomas. This makes the yet to be elucidated eph-related receptor tyrosine
      kinase/Lerk signaling system a potential new source for molecular markers as well
      as a target for new therapies.

PMID- 9533550
TI  - Lineage-negative human leukocyte antigen-DR+ cells with the phenotype of
      undifferentiated dendritic cells in patients with carcinoma of the abdomen and
      pelvis.
AB  - The characteristics of antigen-presenting cells in carcinomas that involve the
      abdominopelvic cavity are unknown. Dendritic cells, a population of antigen
      presenting cells, have been identified as lineage-negative human leukocyte
      antigen (HLA)-DR+ cells by two-color flow cytometry. We used this criterion to
      study the putative dendritic cells in ascites from 25 patients with peritoneal
      carcinomatosis. The mean proportion +/- SD of lineage-negative HLA-DR+ cells in
      ascites was 3.1 +/- 4.6% (range, 0.05-17.3%). Most lineage-negative HLA-DR+ cells
      expressed CD45RA or CD4 antigens. Dendritic cells had low proportions of CD80,
      CD11c, CD45RO, and CD58, suggesting that they were of low maturity. The
      proportion of lineage-negative HLA-DR+ cells in ascites of seven patients was
      significantly higher than the proportion in peripheral blood from the identical
      patients (4.5 +/- 5.7 versus 0.5 +/- 0.4; P < 0.05). In paired specimens of
      ascites and peripheral blood, the proportion of lineage-negative HLA-DR+ cells
      that coexpressed CD86 or CD58 was significantly lower in ascites than in
      peripheral blood, whereas a higher proportion of lineage-negative HLA-DR+ cells
      in ascites expressed CD4. Relative fluorescence intensity of HLA-DR+ was also
      lower in dendritic cells from ascites and blood from patients with carcinomatosis
      than it was in blood from normal donors. As an indicator of macrophage
      activation, the concentration of neopterin in ascitic fluid correlated negatively
      with the numbers of lineage-negative HLA-DR+ cells in ascites (Spearman
      correlation coefficient, -0.44; P = 0.05) correlated positively with the
      concentration of interleukin 10 in ascitic fluid (Spearman correlation
      coefficient, -0.40; P = 0.05). IFN-gamma and tumor necrosis factor alpha were
      also not detected. These findings suggest that certain factors associated with
      the tumor microenvironment might influence the number of these dendritic cells
      and their expression of function-associated markers.

PMID- 9533552
TI  - West syndrome: etiological and prognostic aspects.
AB  - West syndrome is a multi-etiological condition. Recent progress in perinatal
      medicine and the recent development of new neuroimaging techniques may have
      changed the etiological panorama of West syndrome. Our recent study has disclosed
      an increasing percentage of the perinatal group and a decreasing percentage of
      the doubtful group. The increase of the perinatal group is due to an increased
      proportion of very low-birthweight infants and periventricular leucomalacia
      (PVL). Among various etiological factors added to the long list of causes of West
      syndrome, focal cortical dysplasia is another newly emerging etiological factor
      associated with this syndrome. Patients with unilateral focal dysplasia more
      commonly have partial seizures, but may show infantile spasms transiently during
      infancy. They may have partial seizures preceding, in combination with or
      following infantile spasms. Follow-up MRI is necessary to detect delayed
      myelination because it is not disclosed at common ages of onset of this syndrome.
      PET is useful to further differentiate the cryptogenic group. Although West
      syndrome is regarded as one of the intractable epilepsies, the prognosis differs
      widely according to etiology. Follow-up PET is also useful to predict seizure and
      psychomotor prognosis.

PMID- 9533551
TI  - Homozygous deletion of the PTEN tumor suppressor gene in a subset of prostate
      adenocarcinomas.
AB  - A novel tumor suppressor gene, PTEN, which encodes a dual-specificity protein
      phosphatase, has recently been identified on chromosome 10q23. We have previously
      shown that both alleles of this gene are inactivated in three of four prostate
      cancer cell lines tested. To evaluate the role of inactivation of this gene in
      primary stage B prostate cancers, 60 cases were analyzed using Southern blotting
      with PTEN probes and microsatellites on 10q23. Eight of 60 cases had homozygous
      deletions by Southern blotting. In three of these cases, homozygous deletion was
      confirmed by apparent retention of heterozygosity at PTEN with loss of
      heterozygosity at telomeric and centromeric loci. In the remaining five cases,
      microsatellite analysis was consistent with homozygous deletion. Loss of
      heterozygosity at PTEN was found in only two cases both by microsatellite
      analysis and quantitative Southern blotting. No small mutations within PTEN exons
      were found in any tumors exhibiting alterations on 10q23. Thus, inactivation of
      the PTEN gene by homozygous deletion occurs in approximately 10-15% of primary
      stage B prostate carcinomas.

PMID- 9533553
TI  - Episodic ataxia and channelopathies.
AB  - Clinical details are given of different types of episodic ataxia: type 1, with
      myokymia, and attacks which usually last a few minutes, and may occur several
      times a day, and treatment with acetazolamide can reduce the number of attacks;
      type 2, with interictal nystagmus, and attacks which last for several hours to a
      day or more, and treatment with acetazolamide is very effective; paroxysmal
      choreoathetosis with episodic ataxia, with attacks lasting for about 20 min and
      occurring at varying intervals; and familial hemiplegic migraine, with transient
      hemiplegia presenting during the aura of a migraine headache, the symptoms
      improving on treatment with acetazolamide. Their inheritance is of dominant type;
      and the gene for type 1 is mapped to chromosome 12p near to a cluster of
      potassium channel genes, and that for type 2 and for familial hemiplegic migraine
      to chromosome 19p near to calcium channel genes. The differential diagnosis from
      other conditions with a periodic symptomatology is discussed, especially from a
      number of metabolic disorders. Treatment is effective for many of these, and the
      treatment of the episodic ataxias with acetazolamide can sometimes have a
      dramatic effect. The possible role of the channelopathies in the causation of
      some periodic neurological disorders is considered; with the expectation that
      further research will improve the identification of specific diseases, and lead
      to more effective treatment.

PMID- 9533554
TI  - Analysis of childhood epileptic encephalopathies with regard to etiological and
      prognostic factors.
AB  - To analyse the clinical characteristics of patients with childhood epileptic
      encephalopathies, a retrospective study was carried out on paediatric neurology
      clinic records of a tertiary hospital. Forty-five children with childhood
      epileptic encephalopathies were identified. Patients were classified according to
      the international classification of epilepsies and epileptic syndromes, data were
      collected regarding age at onset, perinatal problems, presence of psychomotor
      retardation, radiological findings, etiology and response to therapy.
      Characteristics of responders versus non-responders were compared. The majority
      had West syndrome (29/45 or 64.4%). Of the total, 37/45 or 82.2% were
      symptomatic. The etiologic factors identified included perinatal problems in
      24/45 or 53.3%, one patient with tuberous sclerosis and one with Aicardi's
      syndrome. Psychomotor retardation was seen in 95.5%. Cranial CT scan was normal
      in 11/26 or 42.3%. Abnormalities included infarcts (4/26), generalised atrophy
      and hydrocephalus (3/26), porencephalic cysts (2/26) and agenesis of corpus
      callosum, tuberous sclerosis, gliosis and subdural effusion (one each). Mean
      follow-up was 18 months and 71.4% responded to ACTH. There was no significant
      difference between responders and non-responders.

PMID- 9533555
TI  - Early intervention for very-low-birth-weight infants.
AB  - To assess the efficacy of early intervention (EI) for very-low-birth-weight
      (VLBW) infants, we evaluated 62 2 year old children who were enrolled in an EI
      program and 48 control subjects aged 2 years. We determined the subjects'
      developmental quotients (DQ) and obtained information about the parents'
      evaluation of the children from a questionnaire sent to the parents. There was no
      significant difference in the DQ between the EI group and the control group.
      However, based on the responses to the questionnaire, subjects in the EI group
      showed slight, but statistically marginally significant, improvements in
      behavioral problems, especially a decrease in hyperkinesia, in adjusting to a
      circadian sleep cycle, and an improvement in language development, as compared
      with the control group (P < 0.1). Thus, EI for VLBW infants is considered useful
      to enhance some areas of development.

PMID- 9533556
TI  - Decreased expression of microtubule-associated protein 5 (MAP5) in the molecular
      layer of cerebellum in preterm infants with olivocerebellar lesions.
AB  - The changes in microtubule-associated protein 5 (MAP5) expression in the
      cerebellum with olivocerebellar degeneration (OCD) were investigated by means of
      immunohistochemical method, compared with gestational age-matched controls. In
      controls of 24-33 postmenstrual weeks, the molecular layer was diffusely
      immunoreactive. However, in cases of olivocerebellar degeneration (25-35
      postmenstrual weeks), MAP5 immunoreactivity was reduced in the inner half of the
      molecular layer, especially in a portion where Purkinje cells were absent. The
      ratio of the density in the outer half of the molecular layer to that in the
      inner half was also determined with an image analyzer, and increased
      significantly in Purkinje cell-negative areas. Because MAP5 was believed to be
      expressed mainly on growing axons in the early fetal period, the reduction of
      MAP5 immunoreactivity in OCD cases suggested that normal interaction of Purkinje
      cells and climbing fibers is vulnerable to ischemia and hypoxia in developing
      stage and that retrograde transynaptic degeneration of the inferior olivary
      nuclei is secondarily induced.

PMID- 9533557
TI  - Topographic mapping and clinical analysis of benign childhood epilepsy with
      centrotemporal spikes.
AB  - We studied the topographic mapping of the electroencephalography (EEG) of 47
      children whose clinical history and course were compatible with typical benign
      childhood epilepsy with centrotemporal spikes (BCECT). Twenty-nine (62%) patients
      showed typical dipole fields, with a negative potential field in the
      centrotemporal region and a positive field in the frontal region. Eighteen
      children did not demonstrate the typical dipole field. Their non-dipole rolandic
      discharges were localized in small fields of centrotemporal region. The patients
      with dipole fields in BCECT had significantly less frequent seizures than
      patients without dipole fields. Twelve of the 47 patients with BCECT (26%) had
      more than one EEG focus. The clinical courses of patients with multiple foci were
      not worse than those of patients with a single focus. We conclude that EEG
      topographic mapping is helpful in identifying typical or atypical EEG topographic
      patterns in patients with clinically diagnosed BCECT. We also conclude that the
      presence of dipole field usually indicates a better clinical course of epilepsy
      and multiple foci do not mean a poor clinical course.

PMID- 9533558
TI  - Ineffectiveness of oral coenzyme Q10 supplementation in 3-methylglutaconic
      aciduria, type 3.
AB  - Coenzyme Q10 was administered under placebo controlled blinded crossover
      conditions to six subjects suffering from type 3 3-methylglutaconic aciduria
      ('optic atrophy plus'), following a report of benefit. Despite attainment of high
      plasma levels of coenzyme Q10, no clinical benefit was observed and there was no
      diminution of urinary excretion of 3-methylglutaconic acid.

PMID- 9533559
TI  - Hypomelanosis of ITO. A study of 76 infantile cases.
AB  - We show the complications observed in a large series of children with
      hypomelanosis of Ito (HI) or incontinentia pigmenti achromians, studied in a
      neurology service over 30 years. Of the 76 patients, 35 were male (46%) and 41
      female (54%) with ages ranging from newborn to 10 years at the time of the first
      visit. They were thoroughly studied from the clinical, genetic, psychological,
      neuroradiological, with computed tomography (CT) and/or magnetic resonance
      imaging (MRI), and electroencephalographic (EEG) points of view. Mental
      retardation was observed in 43 cases (57%) of whom eight (10%) showed autistic
      behavior; 16 (21%) were borderline and only 17 (22%) had a normal mental level
      (IQ > 85). Thirty-seven patients (49%) had seizures, consisting of infantile
      spasms in six cases (8%). Twelve cases showed macrocephaly and coarse facies, six
      had microcephaly, and 14 showed hypotonia with pes valgus and genu valgus. Three
      cases of cerebellar hypoplasia, another of intracranial arteriovenous
      malformation and another of distal spinal muscular atrophy were observed as well.
      Some other anomalies, such as syndactyly, clinodactyly, abnormalities of the
      skeleton, asymmetry of the facies, ears, body and/or extremities, gynecomastia
      and asymmetrical breasts, short stature, oral alterations, congenital
      cardiopathies and genital anomalies, were also occasionally found. Three children
      died, but necropsy was performed only in one. Anatomical and histological studies
      did not disclose specific findings.

PMID- 9533560
TI  - Correlation between the M and F wave characteristics and the innervated muscle
      strength in spinal muscular atrophy.
AB  - The purpose of this study is to elucidate the interrelation between the M and F
      wave characteristics of the median nerve and the grip power in patients with
      spinal muscular atrophy (SMA). The SMA patients showed decreased amplitudes of
      the M and F waves, decreased frequency of the F wave, and an increase of the F/M
      ratio as compared with the normative values. The F wave frequency and the
      amplitudes of M and F waves, which showed a significant linear correlation with
      each other, became lower in accordance with the decrease of grip power. The
      properties of M and F waves strongly correlated with the number of surviving
      motor neurons which would be fewer in those severely affected by SMA.

PMID- 9533561
TI  - Nephrogenic diabetes insipidus and tethered cord syndrome with a lipoma of the
      cauda equina.
AB  - The tethered cord syndrome is characterized by sensory and motor disturbances of
      the lower extremities and incontinence. We report a 12-year-old girl with a cauda
      equina lipoma and a tethered spinal cord, whose chief complaints were polyuria
      and polydipsia. She was diagnosed as having nephrogenic diabetes insipidus. This
      unusual complication of the tethered cord syndrome was most likely due to a
      hydronephrosis secondary to a neurogenic bladder. Thus, spinal lesions have to be
      considered in patients with polyuria and polydipsia.

PMID- 9533562
TI  - Accumulation of cholesterol and GM2 ganglioside in cells cultured in the presence
      of progesterone: an implication for the basic defect in Niemann-Pick disease type
      C.
AB  - Cultured fibroblasts from patients with Niemann-Pick disease type C (NP-C) are
      characterized by lysosomal accumulation of unesterified cholesterol and a defect
      in intracellular trafficking of cholesterol. We have found the accumulation of
      GM2 ganglioside in NP-C fibroblasts [Yano T, Taniguchi M, Akaboshi S, Vanier MT,
      Tai T, Sakuraba H, et al. Proc Japan Acad 1996;72B:214-219]. In this
      communication we show that several inhibitors known to inhibit intracellular
      cholesterol transport, progesterone, imipramine and KN-62, elicit accumulation of
      not only unesterified cholesterol but also GM2 ganglioside. This finding suggests
      that intracellular transport of cholesterol may be coupled with that of GM2
      ganglioside. The accumulation of free cholesterol and GM2 ganglioside may be a
      clue for understanding the basic defect of NP-C. Recently NPC1 gene is found by
      the positional cloning. The mechanism of accumulating of GM2 ganglioside should
      be further investigated by studying of the functions of NPC1 gene.

PMID- 9533563
TI  - Different selenium-containing proteins in the extracellular and intracellular
      media of leucocytes cultivated in vitro.
AB  - The purpose of this communication is to elucidate if selenium plays a role in the
      function of granulocytes and lymphocytes. Thus, the incorporation of selenium in
      proteins from granulocytes and lymphocytes cultured with 1 microCi/mL radioactive
      Na2(75)SeO3 was studied. The protein peaks containing 75Se from two columns of
      Heparin Sepharose CL-6B and Sephacryl S-200 HR were separated further by sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis. The
      results showed that the incorporation of 75Se into granulocytes was about six
      times higher than that of lymphocytes during a 96-h cultivation, however, the GSH
      Px activity in granulocytes did not change significantly. On the other hand, the
      GSH-Px activity of lymphocytes rose significantly after three days cultivation.
      These data indicated that the main chemical form of selenium in granulocytes was
      not GSH-Px. Results from SDS-PAGE revealed a strongly 75Se-labeled protein band
      with subunit molecular weight of 15 kDa in the supernatant of granulocyte
      homogenate. However, the main chemical forms of selenium in the culture media of
      granulocytes and lymphocytes were found to be selenoprotein P. The different
      forms of selenium-containing proteins in the intracellular and extracellular
      media of granulocytes indicated the different functions of these proteins.

PMID- 9533564
TI  - Nickel deficiency alters nickel flux in rat everted intestinal sacs.
AB  - This study was conducted to determine nickel absorption in nickel-deficient rats.
      Jejunal segments obtained from dietary nickel-depleted (13 microg nickel/kg diet)
      and nickel-control (1 mg nickel/kg diet) adult rats from the first generation,
      and suckling pups from the second offspring were used. The nickel transfer across
      the intestinal epithelium and nickel uptake into the intestine were measured by
      use of everted jejunal sacs using a wide range of nickel concentrations
      administered on the luminal side (1.1 x 10(-8) M til 1.0 x 10(-4) M). Both the
      intestinal nickel transfer and nickel uptake were influenced by the dietary
      nickel supply in rat offspring, but not in the adult rats from the first
      generation. However, in nickel-deficient offspring, the nickel transfer across
      the small intestine was higher than in nickel-control offspring. This difference
      was greater using low intraluminal nickel concentrations than high nickel
      concentrations, and was significant at 1.1 x 10(-8) M, 6.1 x 10(-8) M, 5.1 x 10(
      7) M, 1.0 x 10(-6) M, and 5.0 x 10(-6) M. Also, nickel uptake into the intestine
      was somewhat greater in nickel-deficient rat pups than in nickel-control pups,
      and significant using 1.1 x 10(-7) M and 1.0 x 10(-6) M nickel. A definite
      saturation type kinetic for the intestinal nickel absorption in relation to the
      intraluminal nickel concentration could not be observed.

PMID- 9533565
TI  - Separation of cellular iron containing compounds by electrophoresis.
AB  - High resolution separation of metalloproteins and other iron compounds based on
      native gel electrophoresis followed by 59Fe autoradiography is described. Lysates
      of mouse spleen erythroid cells metabolically labeled with 59Fe-transferrin were
      separated on 3-20% polyacrylamide gradient gels in the presence of Triton X100
      and detected by autoradiography. In addition to ferritin and hemoglobin, several
      compounds characterized by their binding of iron under different conditions were
      described. Iron chelatable by desferrioxamine migrated in the region where
      several high-molecular weight compounds were detected by silver staining. The
      technique is nondissociative, allowing identification of iron compounds with the
      use of specific antibodies. Cellular iron transport and the action of iron
      chelators on specific cellular targets can be investigated in many small
      biological samples in parallel.

PMID- 9533566
TI  - Determination of the daily selenium intake in Slovakia.
AB  - Three models were used to determine the daily dietary Selenium intake in
      Slovakia. The Selenium content of food produced and consumed in the Slovak
      Republic was used to estimate and calculate the daily Selenium intake based on
      food consumption data per capita and seven days, (24 h) eating protocol models.
      In a duplicate portion model, Selenium was analyzed in a whole day hospital diet
      during an eight-day period. According to these models the daily dietary Selenium
      intake was 38.2 microg; 43.3 +/- 6.5 microg for men and 32.6 /- 6.6 microg for
      women; 27.1 +/- 7.8 microg for normal and 32.3 +/- 4.8 microg for nourishing
      hospital diets. The main contributors of Selenium to daily intake were the
      following: eggs, pork, and poultry. The obtained results indicate that the daily
      dietary intake of Selenium of the Slovak people is below the recommended values.

PMID- 9533567
TI  - Influence of selenium deficiency on vital functions in rats.
AB  - To clarify the relationship between selenium (Se) deficiency and functional
      disorders, the authors determined the Se concentration, anti-oxidant enzyme
      activity, and other parameters in rats fed a Se-deficient diet. Rats fed the Se
      deficient diet showed a decrease in Se concentration and glutathione peroxidase
      (GSH-Px) activity in plasma, erythrocytes, heart, liver, and skeletal muscle from
      the first week after the initiation of the diet, an increase in heart lipid
      peroxide concentration from the second week, and an increase in liver glutathione
      S-transferase activity from the fourth week. From the twelfth week, a decrease in
      the growth rate in the rats fed the Se-deficient diet was observed. In spite of
      this growth impairment, no changes in electrocardiogram, muscle tone, degree of
      hemolysis, plasma biochemistry, or hematological values were detected. In
      summary, the authors found that a reduction of body Se is easily induced, but
      that the appearance of functional disorders following Se deficiency is difficult
      to detect in rats.

PMID- 9533568
TI  - Effects of zinc supplementation on the plasma glucose level and insulin activity
      in genetically obese (ob/ob) mice.
AB  - The effects of zinc supplementation (20 mM ZnCl2 from the drinking water for
      eight weeks) on plasma glucose and insulin levels, as well as its in vitro effect
      on lipogenesis and lipolysis in adipocytes were studied in genetically obese
      (ob/ob) mice and their lean controls (+/?). Zinc supplementation reduced the
      fasting plasma glucose levels in both obese and lean mice by 21 and 25%,
      respectively (p < 0.05). Fasting plasma insulin levels were significantly
      decreased by 42% in obese mice after zinc treatment. In obese mice, zinc
      supplementation also attenuated the glycemic response by 34% after the glucose
      load. The insulin-like effect of zinc on lipogenesis in adipocytes was
      significantly increased by 80% in lean mice. However, the increment of 74% on
      lipogenesis in obese mice was observed only when the zinc plus insulin treatment
      was given. This study reveals that zinc supplementation alleviated the
      hyperglycemia of ob/ob mice, which may be related to its effect on the
      enhancement of insulin activity.

PMID- 9533569
TI  - Effect of trace metals on the restoration potential of leaves of the medicinal
      plant, Portulaca oleracea Linn.
AB  - The effect of Cd, Cu, Zn, Hg, and Pb solutions at various concentrations, on the
      restoration potential of the leaves of Portulaca oleracea was tested. All the
      trace metals completely affected the shoot regeneration. The degree of their
      effect on root regeneration, however, varied. Early initiation of parental leaf
      decay was also observed. The order of their relative effect on the regeneration
      process was: Cd > Cu > Zn > Hg > Pb.

PMID- 9533570
TI  - Blood levels of copper, iron, zinc, and lead in adults in India and Pakistan and
      the effect of oral zinc supplementation for six weeks.
AB  - Deficiency in the intake of trace elements, such as copper (Cu), iron (Fe),
      selenium (Se), and zinc (Zn), is very common in the general population of most
      developing countries. A preliminary study in India and Pakistan showing the
      plasma levels of Zn and Fe indicates that approx 50% of the subjects who
      participated have low levels of both Fe and Zn, suggesting a marginal deficiency.
      The low plasma levels of these elements are more pronounced in females. The mean
      levels of Ze, Cu, and Fe in the plasma of 83 subjects were 0.71 +/- 0.11, 0.96 +/
      0.10, and 0.80 +/- 0.12 mg/L, respectively. The Cu:Zn ratio in the plasma was
      1.43 +/- 0.16. Three groups of 15 subjects each were given three different levels
      of oral supplements of Zn (15, 30, and 45 mg of Zn as Zn gluconate) for 6 wk, and
      blood samples were analyzed during various intervals. Plasma concentration of Zn
      increased significantly (p < 0.001) in all the groups after 4 wk of
      supplementation and reached almost normal levels after 6 wk. Along with the
      increase in Zn, there was a significant decrease (p < 0.001) in plasma Cu levels.
      There were no changes in the concentration of Fe during the supplementation
      period. The supplementation was well tolerated by most subjects. The results of
      this pilot study indicate that Zn supplementation is a practical possibility
      comparable to that of Fe supplementation in order to prevent marginal Zn
      deficiency in vulnerable groups in the general population of developing
      countries.

PMID- 9533571
TI  - Signal analysis and compression performance evaluation of pathological
      microscopic images.
AB  - Digitizing high-quality microscopic images and developing input/output technology
      for displaying those results is critical to telepathology in which pathological
      microscopic images are transferred to remote locations where they are diagnosed
      by specialists. This paper will discuss the results achieved by directly
      digitizing (nonfilm process) pathological microscopic images at a 2k x 2k
      resolution, and then using a super-high-definition imaging system to analyze
      their signals and evaluate compression performance. We will start off by
      digitizing samples that a pathologist will actually use in making a diagnosis,
      and then analyze their color distribution and spatial frequencies characteristics
      by comparing them to general images. This will make it apparent that such
      pathological images characteristically contain high spatial frequency in their
      chrominance components. We will also discuss the evaluation results of color
      differences for L*a*b* space and compression ratios achieved when using JPEG to
      encode pathological images. We will also present a subjective evaluation of the
      influence subsampling of chrominance components has on image quality.

PMID- 9533572
TI  - Analysis of skin erythema using true-color images.
AB  - This article presents a new method for analyzing the spreading of skin erythemas.
      These occur as a result of the cutaneous vascular axon reflex which can be evoked
      by a noxious stimulation of the skin. Series of true-color images of the observed
      skin patch were recorded using a video camera. The images were digitized and
      stored on computer disk. The delineation of the reddening was segmented for every
      image of the sequence by a newly developed image processing method. Each image
      taken after the noxious stimulation was compared with the baseline before the
      stimulation and each image point was classified as: "unchanged" or "changed skin
      color." To improve the classification the CIE L*a*b* color space was used. The
      boundaries of the erythema were extracted from the resulting binary images. Every
      image of a sequence was analyzed in the same way in order to follow the time
      course of the flare response. The erythema reaction could be determined in an
      objective way using this methods. The automatically detected flare sizes were
      independent of human observers and had a high spatial and temporal resolution. It
      was used for a crossover study to assess the power of new drugs which modify the
      blood flow of the skin induced by an intradermal histamine application.

PMID- 9533573
TI  - Implementation of a model-based nonuniform scatter correction scheme for SPECT.
AB  - In this paper four scatter-compensation schemes are considered. The four schemes
      are all based on a previously developed two-dimensional (2-D) scatter model.
      Reconstruction is achieved using the iterative expectation-maximization maximum
      likelihood (EM-ML) algorithm. The schemes consist of: 1) including the model in
      both the forward and back projector; 2) just including the model in the forward
      projector; 3) and 4) implementing the model in a subtraction and addition scheme,
      respectively. Monte Carlo simulated projection data are used to test the
      accuracy, convergence properties, and noise properties of the four scatter
      compensation schemes. Data are simulated for both uniformly and nonuniformly
      attenuating objects. The results show that all four correction schemes yield
      images which are similar in terms of accuracy to that obtained from
      reconstructing scatter-free data. The subtraction scheme is shown to converge
      faster than the other compensation schemes, both in terms of iterations and
      actual time required for reconstruction. The scheme in which the model is only
      used in the forward-projector and the scatter-addition scheme both performs
      slightly better, in terms of signal-to-noise ratio (SNR), than the subtraction
      scheme. However, the forward projector scheme requires significantly more CPU
      time for reconstruction. The correction scheme in which the scatter model was
      included in both the forward and backprojectors is shown to produce accurate
      images with SNR's higher than even a perfect scatter rejection scheme. While the
      scatter correction scheme with the model in both the forward projector and
      backprojector has superior noise properties to the other algorithms, the results
      suggest that the faster subtraction/addition schemes will probably prove most
      useful for routine clinical scatter compensation.

PMID- 9533574
TI  - Automatic registration and alignment on a template of cardiac stress and rest
      reoriented SPECT images.
AB  - Single photon emission computed tomography (SPECT) imaging with 201Tl or 99mTc
      agent is used to assess the location or the extent of myocardial infarction or
      ischemia. A method is proposed to decrease the effect of operator variability in
      the visual or quantitative interpretation of scintigraphic myocardial perfusion
      studies. To effect this, the patient's myocardial images (target cases) are
      registered automatically over a template image, utilizing a nonrigid
      transformation. The intermediate steps are: 1) Extraction of feature points in
      both stress and rest three-dimensional (3-D) images. The images are resampled in
      a polar geometry to detect edge points, which in turn are filtered by the use of
      a priori constraints. The remaining feature points are assumed to be points on
      the edges of the left ventricular myocardium. 2) Registration of stress and rest
      images with a global affine transformation. The matching method is an adaptation
      of the iterative closest point algorithm. 3) Registration and morphological
      matching of both stress and rest images on a template using a nonrigid local
      spline transformation following a global affine transformation. 4) Resampling of
      both stress and rest images in the geometry of the template. Optimization of the
      method was performed on a database of 40 pairs of stress and rest images selected
      to obtain a wide variation of images and abnormalities. Further testing was
      performed on 250 cases selected from the same database on the basis of the
      availability of angiographic results and patient stratification.

PMID- 9533575
TI  - Image reconstruction for dynamic PET based on low-order approximation and
      restoration of the sinogram.
AB  - Many image-reconstruction methods have been proposed to improve the spatial
      resolution of positron emission tomography (PET) images and, thus, to produce
      better quantification. However, these techniques, which are designed for static
      images, may be inadequate for good reconstruction from dynamic data. We present a
      simple, but effective, reconstruction approach intended specifically for dynamic
      studies. First, the level of noise in dynamic PET data is reduced by smoothing
      along the time axis using a low-order approximation. Next, the denoised sinograms
      are restored spatially by the method of projections onto convex sets. Finally,
      images are reconstructed from the restored sinograms by ordinary filtered
      backprojection. We present experimental results that demonstrate substantial
      improvements in region-of-interest quantification in actual and simulated
      dopamine D-2 neuroreceptor-imaging studies of a monkey brain.

PMID- 9533576
TI  - Multimodality Bayesian algorithm for image reconstruction in positron emission
      tomography: a tissue composition model.
AB  - The use of anatomical information to improve the quality of reconstructed images
      in positron emission tomography (PET) has been extensively studied. A common
      strategy has been to include spatial smoothing within boundaries defined from the
      anatomical data. We present an alternative method for the incorporation of
      anatomical information into PET image reconstruction, in which we use segmented
      magnetic resonance (MR) images to assign tissue composition to PET image pixels.
      We model the image as a sum of activities for each tissue type, weighted by the
      assigned tissue composition. The reconstruction is performed as a maximum a
      posteriori (MAP) estimation of the activities of each tissue type. Two prior
      functions, defined for tissue-type activities, are considered. The algorithm is
      tested in realistic simulations employing a full physical model of the PET
      scanner.

PMID- 9533577
TI  - Automatic background recognition and removal (ABRR) in computed radiography
      images.
AB  - A novel method to automatically recognize and remove background signals in
      computed radiography (CR) images caused by X-ray collimation during projection
      radiographic examinations is presented. There are three major steps in this
      method. In the first step, a statistical curve is derived based on many
      hierarchical CR sample images as a first approximation to loosely separate image
      and background pixels. Second, signal processing methods, including specific
      sampling, filtering, and angle recognition, are used to determine edges between
      image and background pixels. Third, adaptive parameter adjustments and consistent
      and reliable estimation rules are used to finalize the location of edges and
      remove the background. In addition, this step also evaluates the reliability of
      the complete background removal operation. With this novel method implemented in
      a clinical picture archiving and communication system (PACS) at the University of
      California at San Francisco, we achieved 99% correct recognition of CR image
      background, and 91% full background removal without removing any valid image
      information.

PMID- 9533578
TI  - Contrast mapping and evaluation for electronic X-ray images on CRT display
      monitor.
AB  - Simple chest X rays on film are the most common type of image in medical
      diagnosis. However, amongst the various types of medical X-ray images, they
      require the highest level of display quality due to the fact that the body
      structures they capture on film have varying degrees of permeability to X rays.
      Conventional high-definition digital display technology has not always been able
      to match the quality of such film images. This has been a major impediment
      against progress toward the complete digitization of simple chest X rays. The
      intent of this paper is to examine that, when applied to medical diagnosis of
      chest X rays, super-high-definition (SHD) images (digital images with resolution
      exceeding that of HDTV) are capable of producing a level of quality of diagnostic
      accuracy on a par with conventional film images. We will start out by seeking out
      the overall transmission characteristics of a system that uses digital
      radiography and a film digitizer to digitize images. We will then derive gray
      scale transform characteristics based on the luminance linear method for
      approximating, as closely as possible on a CRT, film images on a light box that
      have wide dynamic range and high luminance. Finally, we will present the results
      of image evaluation experiments using high-definition CRT monitors. These results
      indicate that conventional film images and those on super-high-definition CRT
      monitors have nearly the same quality. They will also show that the contrast
      mapping selected by radiologists and theoretical luminance linear characteristics
      were almost the same except in low-luminance regions. We will also discuss
      radiologists' comments on CRT monitors after they participated in the evaluation
      experiment.

PMID- 9533579
TI  - Fractal modeling and segmentation for the enhancement of microcalcifications in
      digital mammograms.
AB  - The objective of this research is to model the mammographic parenchymal, ductal
      patterns and enhance the microcalcifications using deterministic fractal
      approach. According to the theory of deterministic fractal geometry, images can
      be modeled by deterministic fractal objects which are attractors of sets of two
      dimensional (2-D) affine transformations. The iterated functions systems and the
      collage theorem are the mathematical foundations of fractal image modeling. In
      this paper, a methodology based on fractal image modeling is developed to analyze
      and model breast background structures. We show that general mammographic
      parenchymal and ductal patterns can be well modeled by a set of parameters of
      affine transformations. Therefore, microcalcifications can be enhanced by taking
      the difference between the original image and the modeled image. Our results are
      compared with those of the partial wavelet reconstruction and morphological
      operation approaches. The results demonstrate that the fractal modeling method is
      an effective way to enhance microcalcifications. It may also be able to improve
      the detection and classification of microcalcifications in a computer-aided
      diagnosis system.

PMID- 9533580
TI  - Measures of acutance and shape for classification of breast tumors.
AB  - Most benign breast tumors possess well-defined, sharp boundaries that delineate
      them from surrounding tissues, as opposed to malignant tumors. Computer
      techniques proposed to date for tumor analysis have concentrated on shape factors
      of tumor regions and texture measures. While shape measures based on contours of
      tumor regions can indicate differences in shape complexities between
      circumscribed and spiculated tumors, they are not designed to characterize the
      density variations across the boundary of a tumor. In this paper we propose a
      region-based measure of image edge profile acutance which characterizes the
      transition in density of a region of interest (ROI) along normals to the ROI at
      every boundary pixel. We investigate the potential of acutance in quantifying the
      sharpness of the boundaries of tumors, and propose its application to
      discriminate between benign and malignant mammographic tumors. In addition, we
      study the complementary use of various shape factors based upon the shape of the
      ROI, such as compactness, Fourier descriptors, moments, and chord-length
      statistics to distinguish between circumscribed and spiculated tumors. Thirty
      nine images from the Mammographic Image Analysis Society (MIAS) database and an
      additional set of 15 local cases were selected for this study. The cases included
      16 circumscribed benign, seven circumscribed malignant, 12 spiculated benign, and
      19 spiculated malignant lesions. All diagnoses were proven by pathologic
      examinations of resected tissue. The contours of the lesions were first marked by
      an expert radiologist using X-Paint and X-Windows on a SUN-SPARCstation 2
      Workstation. For computation of acutance, the ROI boundaries were iteratively
      approximated using a split/merge and end-point adjustment technique to obtain the
      best-fitting polygonal approximation. The jackknife method using the Mahalanobis
      distance measure in the BMDP (Biomedical Programs) package was used for
      classification of the lesions using acutance and the shape factors as features in
      various combinations. Acutance alone resulted in a benign/malignant
      classification accuracy of 95% the MIAS cases. Compactness alone gave a
      circumscribed/spiculated classification rate of 92.3% with the MIAS cases.
      Acutance in combination with a moment-based shape measure and a Fourier
      descriptor-based measure gave four-group classification rate of 95% with the MIAS
      cases. The results indicate the importance of including lesion edge definition
      with shape information for classification of tumors, and that the proposed
      measure of acutance fills this need.

PMID- 9533581
TI  - Computer-aided breast cancer detection and diagnosis of masses using difference
      of Gaussians and derivative-based feature saliency.
AB  - A new model-based vision (MBV) algorithm is developed to find regions of interest
      (ROI's) corresponding to masses in digitized mammograms and to classify the
      masses as malignant/benign. The MBV algorithm is comprised of five modules to
      structurally identify suspicious ROI's, eliminate false positives, and classify
      the remaining as malignant or benign. The focus of attention module uses a
      difference of Gaussians (DoG) filter to highlight suspicious regions in the
      mammogram. The index module uses tests to reduce the number of nonmalignant
      regions from 8.39 to 2.36 per full breast image. Size, shape, contrast, and Laws
      texture features are used to develop the prediction module's mass models.
      Derivative-based feature saliency techniques are used to determine the best
      features for classification. Nine features are chosen to define the
      malignant/benign models. The feature extraction module obtains these features
      from all suspicious ROI's. The matching module classifies the regions using a
      multilayer perceptron neural network architecture to obtain an overall
      classification accuracy of 100% for the segmented malignant masses with a false
      positive rate of 1.8 per full breast image. This system has a sensitivity of 92%
      for locating malignant ROI's. The database contains 272 images (12 b, 100 microm)
      with 36 malignant and 53 benign mass images. The results demonstrate that the MBV
      approach provides a structured order of integrating complex stages into a system
      for radiologists.

PMID- 9533582
TI  - Accurate measurement of intrathoracic airways.
AB  - Airway geometry measurements can provide information regarding pulmonary
      physiology and pathophysiology. There has been considerable interest in measuring
      intrathoracic airways in two-dimensional (2-D) slices from volumetric X-ray
      computed tomography (CT). Such measurements can be used to evaluate and track the
      progression of diseases affecting the airways. A popular airway measurement
      method uses the "half-max" criteria, in which the gray level at the airway wall
      is estimated to be halfway between the minimum and maximum gray levels along a
      ray crossing the edge. However, because the scanning process introduces blurring,
      the half-max approach may not be applicable across all airway sizes. We propose a
      new measurement method based on a model of the scanning process. In our approach,
      we examine the gray-level profile of a ray crossing the airway wall and use a
      maximum-likelihood method to estimate the airway inner and outer radius. Using CT
      scans of a physical phantom, we present results showing that the new approach is
      more accurate than the half-max method at estimating wall location for thin
      walled airways.

PMID- 9533583
TI  - Method for segmenting chest CT image data using an anatomical model: preliminary
      results.
AB  - We present an automated, knowledge-based method for segmenting chest computed
      tomography (CT) datasets. Anatomical knowledge including expected volume, shape,
      relative position, and X-ray attenuation of organs provides feature constraints
      that guide the segmentation process. Knowledge is represented at a high level
      using an explicit anatomical model. The model is stored in a frame-based semantic
      network and anatomical variability is incorporated using fuzzy sets. A blackboard
      architecture permits the data representation and processing algorithms in the
      model domain to be independent of those in the image domain. Knowledge
      constrained segmentation routines extract contiguous three-dimensional (3-D) sets
      of voxels, and their feature-space representations are posted on the blackboard.
      An inference engine uses fuzzy logic to match image to model objects based on the
      feature constraints. Strict separation of model and image domains allows for
      systematic extension of the knowledge base. In preliminary experiments, the
      method has been applied to a small number of thoracic CT datasets. Based on
      subjective visual assessment by experienced thoracic radiologists, basic anatomic
      structures such as the lungs, central tracheobronchial tree, chest wall, and
      mediastinum were successfully segmented. To demonstrate the extensibility of the
      system, knowledge was added to represent the more complex anatomy of lung lesions
      in contact with vessels or the chest wall. Visual inspection of these segmented
      lesions was also favorable. These preliminary results suggest that use of expert
      knowledge provides an increased level of automation compared with low-level
      segmentation techniques. Moreover, the knowledge-based approach may better
      discriminate between structures of similar attenuation and anatomic contiguity.
      Further validation is required.

PMID- 9533584
TI  - Estimation of deformation gradient and strain from cine-PC velocity data.
AB  - Phase contrast magnetic resonance imaging (MRI) can provide in vivo myocardial
      velocity field measurements. These data allow densely spaced material points to
      be tracked throughout the whole heart cycle using, for example, the Fourier
      tracking algorithm. To process the tracking results for myocardial deformation
      and strain quantification, we developed a method that is based on fitting the
      tracking results to an appropriate local deformation model. We further analyzed
      the accuracy and precision of the method and provided performance predictions for
      several local models. In order to validate the method and the theoretical
      performance analysis, we conducted controlled computer simulations and a phantom
      study. The results agreed well with expectations. Human heart data were also
      acquired and analyzed, and provided encouraging results. At the signal-to-noise
      ratio (SNR) level and spatial resolution expected in clinical settings, the study
      predicts strain quantification accuracy and precision that may allow the
      technique to become a practical and powerful noninvasive approach for the study
      of cardiac function, although clinically acceptable data acquisition strategies
      for three-dimensional (3-D) data are still a challenge.

PMID- 9533585
TI  - Creating connected representations of cortical gray matter for functional MRI
      visualization.
AB  - We describe a system that is being used to segment gray matter from magnetic
      resonance imaging (MRI) and to create connected cortical representations for
      functional MRI visualization (fMRI). The method exploits knowledge of the anatomy
      of the cortex and incorporates structural constraints into the segmentation.
      First, the white matter and cerebral spinal fluid (CSF) regions in the MR volume
      are segmented using a novel techniques of posterior anisotropic diffusion. Then,
      the user selects the cortical white matter component of interest, and its
      structure is verified by checking for cavities and handles. After this, a
      connected representation of the gray matter is created by a constrained growing
      out from the white matter boundary. Because the connectivity is computed, the
      segmentation can be used as input to several methods of visualizing the spatial
      pattern of cortical activity within gray matter. In our case, the connected
      representation of gray matter is used to create a flattened representation of the
      cortex. Then, fMRI measurements are overlaid on the flattened representation,
      yielding a representation of the volumetric data within a single image. The
      software is freely available to the research community.

PMID- 9533586
TI  - Volumetric transformation of brain anatomy.
AB  - This paper presents diffeomorphic transformations of three-dimensional (3-D)
      anatomical image data of the macaque occipital lobe and whole brain cryosection
      imagery and of deep brain structures in human brains as imaged via magnetic
      resonance imagery. These transformations are generated in a hierarchical manner,
      accommodating both global and local anatomical detail. The initial low
      dimensional registration is accomplished by constraining the transformation to be
      in a low-dimensional basis. The basis is defined by the Green's function of the
      elasticity operator placed at predefined locations in the anatomy and the
      eigenfunctions of the elasticity operator. The high-dimensional large
      deformations are vector fields generated via the mismatch between the template
      and target-image volumes constrained to be the solution of a Navier-Stokes fluid
      model. As part of this procedure, the Jacobian of the transformation is tracked,
      insuring the generation of diffeomorphisms. It is shown that transformations
      constrained by quadratic regularization methods such as the Laplacian,
      biharmonic, and linear elasticity models, do not ensure that the transformation
      maintains topology and, therefore, must only be used for coarse global
      registration.

PMID- 9533587
TI  - Markov random field segmentation of brain MR images.
AB  - We describe a fully-automatic three-dimensional (3-D)-segmentation technique for
      brain magnetic resonance (MR) images. By means of Markov random fields (MRF's)
      the segmentation algorithm captures three features that are of special importance
      for MR images, i.e., nonparametric distributions of tissue intensities,
      neighborhood correlations, and signal inhomogeneities. Detailed simulations and
      real MR images demonstrate the performance of the segmentation algorithm. In
      particular, the impact of noise, inhomogeneity, smoothing, and structure
      thickness are analyzed quantitatively. Even single-echo MR images are well
      classified into gray matter, white matter, cerebrospinal fluid, scalp-bone, and
      background. A simulated annealing and an iterated conditional modes
      implementation are presented.

PMID- 9533588
TI  - Volumetric object reconstruction using the 3D-MRF model-based segmentation.
AB  - A number of segmentation algorithms have been developed, but those algorithms are
      not effective on volume reconstruction because they are limited to operating only
      on two-dimensional (2-D) images. In this paper, we propose the volumetric object
      reconstruction method using the three-dimensional Markov random field (3D-MRF)
      model-based segmentation. The 3D-MRF model is known to be one of efficient ways
      to model spatial contextual information. The method is compared with the 2-D
      region growing scheme under three types of interpolation. The results show that
      the proposed method is better in the aspect of image quality than other methods.

PMID- 9533589
TI  - Pseudo-Fourier imaging (PFI): a technique for spatial encoding in MRI.
AB  - In magnetic resonance imaging (MRI), spatial discrimination is usually achieved
      with selective excitation and/or Fourier encoding. While these approaches are
      favorable in most situations, it is sometimes desirable to have an approach that
      takes advantage of both selective excitation and Fourier encoding. In this paper,
      we describe the theory and experimental results of a new technique, which we will
      call pseudo-Fourier imaging (PFI), that provides a flexible combination of both
      approaches. The technique is based on a windowed Fourier transform that expands
      the continuous object spatial distribution in terms of coherent states. A
      detailed description of the proposed technique is presented in this paper. The
      practical implementation of this technique is described and shown to be
      achieveable using a set of selective excitations combined with a number of
      Fourier encoding steps. Then, the signal-to-noise ratio of the new technique is
      derived to show that it can be varied at will anywhere in the range between the
      ratios for selective excitation and Fourier encoding. Finally, the experimental
      results of implementing the technique are presented and some potential
      applications of the technique such as volume imaging, dynamic imaging and
      magnetic resonance angiography are discussed.

PMID- 9533590
TI  - Automatic correction of motion artifacts in magnetic resonance images using an
      entropy focus criterion.
AB  - We present the use of an entropy focus criterion to enable automatic focusing of
      motion corrupted magnetic resonance images. We demonstrate the principle using
      illustrative examples from cooperative volunteers. Our technique can determine
      unknown patient motion or use knowledge of motion from other measures as a
      starting estimate. The motion estimate is used to compensate the acquired data
      and is iteratively refined using the image entropy. Entropy focuses the whole
      image principally by favoring the removal of motion induced ghosts and blurring
      from otherwise dark regions of the image. Using only the image data, and no
      special hardware or pulse sequences, we demonstrate correction for arbitrary
      rigid-body translational motion in the imaging plane and for a single rotation.
      Extension to three-dimensional (3-D) and more general motion should be possible.
      The algorithm is able to determine volunteer motion well. The mean absolute
      deviation between algorithm and navigator-echo-determined motion is comparable to
      the displacement step size used in the algorithm. Local deviations from the
      recorded motion or navigator-determined motion are explained and we indicate how
      enhanced focus criteria may be derived. In all cases we were able to compensate
      images for patient motion, reducing blurring and ghosting.

PMID- 9533591
TI  - Automated segmentation and classification of multispectral magnetic resonance
      images of brain using artificial neural networks.
AB  - We present a fully automated process for segmentation and classification of
      multispectral magnetic resonance (MR) images. This hybrid neural network method
      uses a Kohonen self-organizing neural network for segmentation and a multilayer
      backpropagation neural network for classification. To separate different tissue
      types, this process uses the standard T1-, T2-, and PD-weighted MR images
      acquired in clinical examinations. Volumetric measurements of brain structures,
      relative to intracranial volume, were calculated for an index transverse section
      in 14 normal subjects (median age 25 years; seven male, seven female). This index
      slice was at the level of the basal ganglia, included both genu and splenium of
      the corpus callosum, and generally, showed the putamen and lateral ventricle. An
      intraclass correlation of this automated segmentation and classification of
      tissues with the accepted standard of radiologist identification for the index
      slice in the 14 volunteers demonstrated coefficients (ri) of 0.91, 0.95, and 0.98
      for white matter, gray matter, and ventricular cerebrospinal fluid (CSF),
      respectively. An analysis of variance for estimates of brain parenchyma volumes
      in five volunteers imaged five times each demonstrated high intrasubject
      reproducibility with a significance of at least p < 0.05 for white matter, gray
      matter, and white/gray partial volumes. The population variation, across 14
      volunteers, demonstrated little deviation from the averages for gray and white
      matter, while partial volume classes exhibited a slightly higher degree of
      variability. This fully automated technique produces reliable and reproducible MR
      image segmentation and classification while eliminating intra- and interobserver
      variability.

PMID- 9533592
TI  - Reconstruction of vascular networks using three-dimensional models.
AB  - Reconstructing vasculature in three dimensions is a challenging problem. Early
      approaches concentrated on coronary vasculature in X-ray images, recent work uses
      magnetic resonance imagery of cerebral vasculature. In both cases a priori
      information has been used, and often the way this is represented has proven
      limiting to the scope of applications supported. For example, a particular
      representation may be useful only for X-ray images. This paper addresses two
      issues: 1) representing a collection of vasculature and 2) the reconstruction of
      individual vasculature from images. Our representation learns the variations in
      branching structures and vessel shapes that occur between individuals. It
      supports a vascular catalogue containing three-dimensional (3-D) anatomical
      models. The representation is task independent; here we use it to reconstruct
      vasculature from images. Our algorithm has four features to which we draw
      attention: 1) it is not premised wholly upon X-ray images (though that is our
      focus here); 2) it produces several feasible solutions rather than one; 3) it can
      generalize from the catalogue to reconstruct instances not yet learned; 4) it
      exhibits polynomial time complexity, reasonable memory consumption, and is
      reliable. Both our representation and reconstruction algorithm are new and useful
      approaches. In support of these claims, we present results gathered from X-rays
      of both simulated and real vasculature.

PMID- 9533593
TI  - Estimating fractal dimension with fractal interpolation function models.
AB  - Fractal dimension (fd) is a feature which is widely used to characterize medical
      images. Previously, researchers have shown that fd separates important classes of
      images and provides distinctive information about texture. We analyze limitations
      of two principal methods of estimating fd: box-counting (BC) and power spectrum
      (PS). BC is ineffective when applied to data-limited, low-resolution images; PS
      is based on a fractional Brownian motion (fBm) model-a model which is not
      universally applicable. We also present background information on the use of
      fractal interpolation function (FIF) models to estimate fd of data which can be
      represented in the form of a function. We present a new method of estimating fd
      in which multiple FIF models are constructed. The mean of the fd's of the FIF
      models is taken as the estimate of the fd of the original data. The standard
      deviation of the fd's of the FIF models is used as a confidence measure of the
      estimate. We demonstrate how the new method can be used to characterize fractal
      texture of medical images. In a pilot study, we generated plots of curvature
      values around the perimeters of images of red blood cells from normal and sickle
      cell subjects. The new method showed improved separation of the image classes
      when compared to BC and PS methods.

PMID- 9533594
TI  - A novel pulse-echo technique for medical three-dimensional imaging.
AB  - A new pulse-echo imaging technique for close near-field applications is proposed.
      Based on the theory developed for the continuous-wave automatic focusing
      technique (CWAFT), it uses instead, a frequency-domain phase compensation through
      a convolutional mechanism. In addition, the scanned frequencies of the
      transmitted CW signals are sent simultaneously in a pulse that is used for the
      data acquisition and processing. The pulse-echo nature of this technique makes it
      a candidate for further development and evaluation for ultrasonic three
      dimensional (3-D) medical imaging and nondestructive testing. Furthermore, the
      "spike-like" nature of the back propagator in the frequency domain is used to
      half the data acquired. This alleviates most of the drawbacks of the CWAFT in
      data acquisition and processing. Simulation results are presented for both two
      dimensional (2-D) and 3-D targets.

PMID- 9533595
TI  - Limitations of the principal-axes theory.
AB  - The classical principal-axes transformation (PAT) has been used in numerous
      publications for three-dimensional (3-D) reconstructions by sequential alignment
      of histological sections. However, the PAT can determine at most 1/2n(n + 1)
      parameters (scaling-rotation) in n dimensions. Distortions (shearing) of
      histological sections can be described by an affine transformation with n2
      parameters. An analytical model is devised for calculating rotational and scaling
      errors which can be determined by relating the transformation parameters of the
      PAT to the exact solution of a singular value decomposition (SVD) of the
      perturbation matrix. The results show that form and deformation of the form are
      intertwined and that these results can be transferred to real data. The model is
      important for assessing the quality that can be expected with the PAT for 3-D
      reconstructions if no multimodality reference is available (rigid transformation)
      and reveals the misalignment in terms of rotational and scaling errors resulting
      from the PAT as derived in a previously published paper.

PMID- 9533596
TI  - Automatic detection of the mid-sagittal plane in 3-D brain images.
AB  - This article presents a detailed description of an algorithm for the automatic
      detection of the mid-sagittal plane in three-dimensional (3-D) brain images. The
      algorithm seeks the plane with respect to which the image exhibits maximum
      symmetry. For a given plane, symmetry is measured by the cross-correlation
      between the image sections lying on either side. The search for the plane of
      maximum symmetry is performed by using a multiresolution approach which
      substantially decreases computational time. The choice of the starting plane was
      found to be an important issue in optimization. A method for selecting the
      initial plane is presented. The algorithm has been tested on brain images from
      various imaging modalities in both humans and animals. Results were evaluated by
      visual inspection by neuroradiologists and were judged to be consistently
      correct.

PMID- 9533597
TI  - CT image enhancement with wavelet analysis for the detection of small airways
      disease.
AB  - Bronchiolar obstruction is commonly manifested in computed tomography (CT) images
      as areas of decreased attenuation relative to adjacent normal lung parenchyma.
      The certain identification of such areas is difficult in practice, particularly
      if they are poorly marginated. This paper presents a novel approach to the
      enhancement of feature differences between normal and diseased lung parenchyma so
      that reliable visual assessment can be made. The method relies on a hybrid
      structural filtering technique which removes pulmonary vessels appearing in the
      CT cross-sectional images without affecting intrinsic subtle intensity details of
      the lung parenchyma. In order to restore possible structural distortions
      introduced by the hybrid filter, a feature localization process based on wavelet
      reconstruction of feature extrema is used. After contrast enhancement the
      resultant images are used to delineate region borders of the diseased areas and
      quantification is made with regard to the extent of the disease.

PMID- 9533598
TI  - Low-tension glaucoma disorders.

PMID- 9533599
TI  - SUNCT, lacrimation, and trigeminal neuralgia.

PMID- 9533600
TI  - Post-lumbar puncture headache.

PMID- 9533601
TI  - Migraine and glaucoma: an epidemiologic survey of French ophthalmologists.
AB  - Glaucoma is a common ocular disorder; a high intraocular pressure is observed in
      the majority of glaucoma (HIOPG) cases, but some patients have low-tension
      glaucoma (LTG). In the literature, some works link LTG and migraine, which is
      speculative of a potential role of a vasospastic factor or diathesis common to
      migraine and LTG. Using a standardized questionnaire based on International
      Headache Society (IHS) criteria, we investigated 954 glaucoma patients; 320
      (33.5%) described a headache (migraine or tension-type headache) and 240 (25.1%)
      presented the IHS criteria for migraine. Migraine prevalence was not
      significantly different between HIOPG and LTG patients (22.8% and 32%,
      respectively) in this study.

PMID- 9533602
TI  - Oculosympathetic alterations in migraine patients.
AB  - Oculosympathetic function was studied in 20 headache-free migraine patients and
      in 20 controls. Pupillary investigation was performed under basal conditions, and
      after instillation of tyramine (2%) and phenylephrine (1%) eyedrops. Each test
      was performed twice shortly after a spontaneous attack and then repeated after 7
      and 15 days. In the patients, the normal mydriatic response induced by tyramine
      was significantly (p<0.001) reduced and phenylephrine instillation caused a
      significant (p<0.01) pupillary dilatation in both the assessments performed
      shortly after the attack. These abnormal responses were bilateral in all patients
      and slightly anisocoric in some. They were significantly (p<0.001) more
      pronounced in the patients who had pain and pronounced vascular features. The
      reduced oculosympathetic response to tyramine, as well as the hypersensitivity to
      phenylephrine, was less evident 7 days after the attack and absent after 15 days.
      A transient and bilateral post-ganglionic oculosympathetic hypofunction, with
      adrenoceptor hypersensitivity, was found to be temporally related to the migraine
      attack, regardless of the side or predominant side of pain.

PMID- 9533603
TI  - Trigeminal neuralgia with lacrimation or SUNCT syndrome?
AB  - An intimate relationship between trigeminal neuralgia (TN) and short-lasting
      unilateral neuralgiform headache attacks with conjunctival injection and tearing
      (SUNCT) syndrome, based on similar clinical signs and symptoms and on cases
      demonstrating possible "transformation" from one entity to the other, has been
      widely accepted. We evaluated the presence of lacrimation in 22 consecutive cases
      that had been diagnosed as TN. Ipsilateral lacrimation was reported by 6 such
      cases (5M, 1F). These cases responded to antineuralgic therapy with concomitant
      resolution of lacrimation and were clinically very similar to TN. The
      differential diagnosis and the possibility of lacrimation in TN are discussed.

PMID- 9533604
TI  - Premonitory and prodromal symptoms in cluster headache.
AB  - Warning symptoms in 150 cluster headache patients were studied by focusing on
      attacks occurring during waking hours. Warnings were divided into prodromes that
      started minutes before the pain of individual attacks (122 patients) and
      premonitory symptoms preceding the onset of cluster periods by days to weeks (12
      patients). Pathogenetic and therapeutic implications are discussed.

PMID- 9533606
TI  - The time course of post-lumbar puncture headache.
AB  - According to the leakage theory, the time taken for pain to develop upon rising
      to the upright position will increase during the time course of post-lumbar
      puncture headache (PPH) as a consequence of the decreasing size of the healing
      dural rent, and the pain will decline. The aim of the present prospective study
      was to test this hypothesis, and to describe the temporal course of time and pain
      variables in PPH. The study showed that the course was fairly stable for all
      variables except on the first day, the second last day, and the last day. In the
      recumbent position, the headache was more severe on the first day (p<0.05) and
      milder on the last day (p<0.001) compared with the interim days; maximal headache
      in the upright position was milder on the second last (p<0.005) and last days
      (p<0.0001). Compared with the interim days, the time prior to increase of pain
      upon rising was shorter on the first day (p<0.05) and longer on the last day
      (p<0.001), and from start of increase until maximum was longer on the last day
      (p<0.01). The time to pain relief upon lying down did not vary significantly
      throughout the PPH period. The mobility of the patient as expressed by the PPH
      grade was fairly stable throughout the course of PPH until it increased in the
      last 2 days. The results are in good accord with the leakage theory.

PMID- 9533605
TI  - Serotonin metabolism in cluster headache.
AB  - Despite some evidence of the involvement of the serotonergic system in cluster
      headache (CH) pathophysiology, the serotonin (5HT) metabolism has so far been
      poorly studied. The aim of this study was to investigate plasma and platelet
      levels of 5HT and 5-hydroxyindoleacetic acid (5HIAA) in CH patients in the active
      period of the disease. Nineteen CH sufferers and 17 sex- and age-matched healthy
      controls were studied. CH patients showed significantly higher plasma levels of
      5HT and 5HIAA compared to controls (5HT: 5.7+/-6.1 ng/ml vs 0.2+/-0.2 ng/ml;
      p=0.02; 5HIAA: 34.7+/-46.1 ng/ml vs 0.6+/-0.7 ng/ml; p=0.004). In platelet 5HT
      levels were slightly reduced in CH patients in comparison with those of control
      subjects (662.4+/-522.3 ng/10(-8) platelets vs 832.4+/-587.9 ng/10(-8) platelets;
      n.s.) and 5HIAA levels resulted significantly lower in CH sufferers than in
      control subjects (3.2+/-2.6 ng/10(-8) platelets vs 6.7+/-4.8 ng/10(-8) platelets;
      p=0.04). Our data suggest that CH is characterized by an increase of plasma
      serotonergic metabolism that could reflect an involvement of the central
      serotonergic system in the pathogenesis of CH.

PMID- 9533607
TI  - The psychological profiles of patients with whiplash-associated headache.
AB  - Headache often compounds chronic neck pain following whiplash injury. To better
      understand post-traumatic headache, the SCL-90-R symptom checklist was used to
      determine the psychological profiles of patients with whiplash-associated
      headache and of patients with whiplash-associated neck pain without headache. The
      psychological profiles of these patients were compared with previously published
      SCL-90-R profiles of patients with post-traumatic and nontraumatic headache, and
      of the normal population. Patients with whiplash-associated headache were not
      significantly different from those with other forms of post-traumatic headache or
      with whiplash-associated neck pain without headache. However, when patients with
      whiplash-associated headache and patients with nontraumatic headache were
      compared to normal data, significant differences emerged. Patients with
      nontraumatic headache exhibited higher scores on all subscales, whereas patients
      with whiplash-associated headache differed from the normal sample only on
      somatization, obsessive-compulsive, depression and hostility subscales, and the
      global severity index. These differences imply that patients with whiplash
      associated headache suffer psychological distress secondary to chronic pain and
      not from tension headache and generalized psychological distress.

PMID- 9533608
TI  - Measurement of muscle hardness: a methodological study.
AB  - The aim of the present study was to determine the intra- and interobserver
      variation during measurement of muscle hardness with a new instrument, a so
      called hardness meter. In addition, we investigated the factors which may
      influence the recording of muscle hardness and whether the hardness differs
      within the same muscle. Hardness was measured at a standardized point on the
      trapezius muscle in 20 volunteers by 2 observers in random order and again by 1
      of the observers after 30 min. Muscle hardness was then measured at 3 different
      locations on the trapezius muscle. In addition, the muscle hardness at the
      standard point was measured in 10 volunteers by both observers at 3 different
      speeds of the applied pressure. The intraobserver variation was 10% and the
      interobserver variation was 12% for recording of muscle hardness. There was no
      significant difference in hardness values from time to time within the same
      observer (p=0.12), while there was a significant difference in hardness
      measurements between observers (p=0.007). Muscle hardness differed significantly
      among the 3 anatomical locations (p=0.03). For both observers, there was a
      significant difference among hardness recordings obtained at 3 different speeds
      (p=0.01 and p=0.0001). In conclusion, we have shown that the hardness meter can
      measure muscle hardness reliably if the same observer is used throughout a study.
      The speed factor was a major source of variability In addition, we have
      demonstrated that muscle hardness differs within the same muscle. We suggest that
      the muscle hardness meter will be an important tool in future research of the
      mechanisms leading to myofascial pain.

PMID- 9533609
TI  - Head pain associated with sixth-nerve palsy: spontaneous dissection of the
      internal carotid artery.

PMID- 9533610
TI  - Brain "ouabain", a neurosteroid, mediates sympathetic hyperactivity in salt
      sensitive hypertension.
AB  - This review addresses recent developments in the neurobiology of an endogenous
      inhibitor of brain Na+, K+ - ATPase, "ouabain". "Ouabain" is present in
      hypothalamic and medullary neurons and mediates sympathoexcitatory and pressor
      responses to acute and chronic increases in cerebrospinal fluid (CSF) sodium
      concentration as well as mediates the sympathoexcitatory and pressor responses to
      high dietary sodium intake in SHR and Dahl-S rats, and sympathetic hyperactivity
      in the congestive heart failure. Some of these actions of "ouabain" in the CNS
      take place in the median preoptic nucleus and ventral part of the AV3V region.
      Despite recent advances in unveiling a biological role for "ouabain" its
      structure, biosynthetic and metabolic pathways as well as actual control
      mechanisms remain unresolved.

PMID- 9533611
TI  - Role of nitric oxide in responses to renin-angiotensin system inhibition in
      sodium-depleted guinea pig and rat.
AB  - Previous reports have suggested that NO is an important mediator of the
      antihypertensive effects of renin-angiotensin system (RAS) inhibition. We
      examined the effects of the NO synthase inhibitor L-NNA on the hypotensive
      effects of captopril, the Ang II antagonist EXP 3174, or the renin inhibitor
      terlakiren. In sodium-depleted guinea pigs (GPs), L-NNA (3 mg/kg) increased MAP
      by 15-21% for at least 5 hours. L-NNA partially blocked the hypotensive effects
      of captopril (1 mg/kg, iv), but not those of EXP 3174 (1 mg/kg, iv) or terlakiren
      (3 mg/kg). In sodium-depleted rats, 10 mg/kg L-NNA (iv) increased MAP by 16-22%,
      and partially or fully blocked the hypotensive effect of EXP 3174 (1 mg/kg, iv)
      or captopril (3 mg/kg, iv), respectively. Thus, in contrast to the rat, NO in GPs
      appears to participate only in the hypotensive action of ACE inhibition and does
      not appear to be strongly involved in the hypotensive action of AII antagonism or
      renin inhibition. The involvement of NO in the hypotensive effects of RAS
      antagonists other than ACE inhibitors may be species-dependent.

PMID- 9533612
TI  - The co-existence of insulin-mediated decreased mean arterial pressure and
      increased sympathetic nerve activity is not mediated by the baroreceptor reflex
      and differentially by hypoglycemia.
AB  - In this study we measured simultaneously and sequentially the lumbar sympathetic
      nerve activity (LSNA) or renal sympathetic nerve activity (RSNA), mean arterial
      pressure (MAP), and heart rate (HR) in response to insulin with co-existing
      hypoglycemia or with glucose replacement in normal rats. Sinoaortic denervation
      (SAD) was used to evaluate the influence of the baroreflex. LSNA, RSNA, MAP and
      HR were determined using an acquisition processor and computer software. Bolus
      insulin infusion where the blood glucose was allowed to decrease resulted in an
      immediate decrease in MAP. The HR decreased for approximately 15 min and
      subsequently increased. The LSNA increased immediately after insulin infusion
      peaking at 25 minutes and then recovered toward baseline. Insulin infusion with
      glucose replacement resulted in a decrease in MAP and HR. The LSNA progressively
      increased and was maintained throughout the experimental period. Insulin infusion
      with hypoglycemia increased RSNA and when hypoglycemia was prevented the RSNA
      decreased. SAD attenuated the decrease in MAP and LSNA response to insulin. Thus,
      insulin acts to decrease MAP while simultaneously increasing HR, LSNA and RSNA
      when hypoglycemia is allowed to occur. However, insulin acts to decrease HR and
      RSNA when euglycemia is maintained. The insulin-induced increase in LSNA is
      modulated by the baroreflex mechanism. We conclude that insulin has independent
      direct and indirect effects on LSNA, RSNA, MAP and HR that are modulated by
      glycemia and the baroreflex.

PMID- 9533613
TI  - Mapping of candidate genes for hypertension by fluorescence in situ hybridization
      on the genome of transgenic rats and mice.
AB  - Transgenic animals are new and important models for the study of candidate genes
      in hypertension research as well as in other fields of medicine. For detailed
      genetic characterization of the transgenic animals, and to account for the
      symptoms arising from the insertion of transgenes in the genome, it is essential
      to identify these insertion sites. In this study, the insertion sites of the
      transgenes of candidate genes for hypertension were identified by fluorescence in
      situ hybridization (FISH) after G-banding of the chromosomes in transgenic rats
      and mice. This technique combines high resolution G-banding and fluorescence in
      situ hybridization for the mapping of four different candidate genes in six
      different transgenic rats as well as three different mouse transgenic lines. The
      presented results will help to draw conclusions about the influence of the
      respective integration site on transgene expression.

PMID- 9533614
TI  - Effects of AT1 receptor blockade on blood pressure and the renin-angiotensin
      system in spontaneously hypertensive rats of the stroke prone strain.
AB  - The aim of the study was to assess the effects of chronic angiotensin I receptor
      blockade on blood pressure, the renin-angiotensin system in plasma and kidney and
      the extent of renal damage in spontaneously hypertensive rats of the stroke prone
      strain (SHRsp). Four months old male SHRsp rats were orally treated with a high
      (10 mg/kg b.w. per day) or a low dose (1 mg/kg b.w. per day) of the AT1 receptor
      antagonist Telmisartan and compared to Losartan- (20 mg/kg b.w. per day),
      Captopril-treated (50 mg/kg b.w. per day) or untreated control groups for 38
      days. Despite a similar extent of blood pressure reduction in all groups (except
      low dose Telmisartan), high dose Telmisartan but not Losartan or Captopril
      significantly reduced left ventricular weight by 24% compared to controls
      (p<0.05). Renal damage as assessed by urinary albumin or glomerulosclerosis index
      was significantly reduced in all treatment groups (p<0.02). Plasma renin
      concentration was significantly elevated (p<0.02) and plasma angiotensinogen
      significantly lowered (p<0.05) in all pharmacologically treated group compared to
      controls. In the kidney, renin-mRNA as well as AT1 receptor gene expression were
      elevated in all treatment groups, but no significant changes were found for renal
      angiotensinogen-mRNA. Chronic oral treatment of genetically hypertensive rats by
      the AT1 receptor antagonist Telmisartan reveals a blood pressure lowering and
      reno-protective effect of this drug comparable to other AT1 receptor antagonists
      or converting enzyme inhibitors, and demonstrates a marked reduction of cardiac
      hypertrophy by Telmisartan in this model.

PMID- 9533615
TI  - Effects of acetylcholine and nitroprusside on systemic and regional hemodynamics
      in hypertensive rats.
AB  - This study was performed to investigate the in vivo effects of acetylcholine, a
      stimulator of endogenous NO production, and nitroprusside, an exogenous NO-donor,
      on hemodynamics in the normotensive (WKY) and the hypertensive (SHR) rat.
      Anesthetized rats were given microspheres for the measurement of cardiac index
      (CI), total vascular resistance (TPRI), regional blood flow and vascular
      resistance. Infusion of acetylcholine (2 microg/kg/min) caused a marked decrease
      in TPRI by (-35+/-5%, +/-SEM) in the WKY (n=8), whereas in the SHR (n=8) a less
      pronounced reduction was seen (-14+/-3%, p<0.01 between groups). CI increased by
      27+/-9% in the WKY, but was unaltered in the SHR. Blood pressure decreased
      similarly (17-20%). Acetylcholine significantly increased blood flow by about 40%
      in the kidneys and the heart in the WKY, but had no significant effect in the
      SHR. Other tissues, such as skeletal muscle and cerebral tissues, showed no major
      changes. Infusion of nitroprusside (1 microg/kg/min) reduced blood pressure by 5
      to 10% in the strains. The regional effects of nitroprusside did not differ
      between the strains. In conclusion, the acetylcholine-induced vasodilation in the
      kidney and the heart was attenuated in the SHR compared to the WKY. These
      findings might suggest a difference in the endothelial response between the SHR
      and the WKY in some, but not in all, tissues.

PMID- 9533616
TI  - Baroreceptor activation causes release of acetylcholine in the rostral
      ventrolateral medulla of the rat.
AB  - We examined whether baroreceptor activation causes a release of acetylcholine
      (ACh) in the rostral ventrolateral medulla (RVLM) of the rat, in order to
      investigate a possible connection between RVLM cholinergic systems and
      cardiovascular baroreflexes. Male Wistar rats were anesthetized, paralyzed and
      artificially ventilated. Either electrical stimulation of aortic nerve or
      baroreceptor activation by intravenous phenylephrine produced an increase of the
      release of ACh in the RVLM, whereas baroreceptor denervation and tetrodotoxin
      (TTX) microinfusion in the RVLM inhibited the increase in ACh release induced by
      phenylephrine. TTX injected in the caudal ventrolateral medulla (CVLM) inhibited
      the phenylephrine-induced increase of ACh release. The excitatory amino acid L
      glutamate microinfused in the CVLM produced an release in ACh release in the
      RVLM. These results suggest that there is a connection between RVLM cholinergic
      systems and cardiovascular baroreflexes. It is probable that neurons in the CVLM
      are involved in mediating the release of ACh in the RVLM.

PMID- 9533617
TI  - Renal nerves and D1-dopamine receptor-mediated natriuresis.
AB  - The resistance of the spontaneously hypertensive rat (SHR) kidney to the
      natriuretic effect of dopamine and D1 agonists may be due to increased renal
      nerve activity. Therefore, we compared the effects of the intrarenal arterial
      infusion of the D1 agonist, SKF 38383, into the denervated (DNX) kidney of saline
      loaded-anesthetized SHR and its control, the Wistar-Kyoto (WKY) rat. In both WKY
      and SHR, DNX of the left kidney slightly decreased urine flow (UV) and absolute
      (UNaV) and fractional sodium excretion (FENa) in the innervated right kidney;
      neither vehicle nor D1 agonist infusion exerted any effect. In the left kidney,
      denervation increased UV, UNaV, and FENa to a similar degree in WKY and SHR (2
      fold), without affecting renal blood flow, glomerular filtration rate, or blood
      pressure. In WKY but not in SHR, after DNX, the D1 agonist dose-dependently
      increased UV, UNaV, and FENa in the denervated kidney. We conclude that the
      decreased natriuretic effect of D1 agonists in the SHR is not due to increased
      renal nerve activity. These data support our previous studies implicating a
      defect of the D1 receptor or its regulation in the kidney in genetic
      hypertension.

PMID- 9533618
TI  - GLASS: a tool to visualize protein structure prediction data in three dimensions
      and evaluate their consistency.
AB  - When a protein sequence does not share any significant sequence similarity with a
      protein of known structure, homology modeling cannot be applied. However, many
      novel and interesting methods, such as secondary structure prediction, fold
      recognition, and prediction of long-range interactions, are being developed and
      have been shown to be reasonably successful in predicting protein structures from
      sequence data and evolutionary information. The a priori evaluation of the
      correctness of a prediction obtained by one of these methods is however often
      problematic. Consequently, it is important to use all available information
      provided by as many different methods as possible and all the available
      experimental data about the protein of interest, since the consistency of the
      results is indicative of the reliability of the prediction. Hence the need has
      arisen for suitable tools able to compare results provided by different methods
      and evaluate their consistency. We have therefore constructed GLASS, a general
      platform to read, visualize, compare, and evaluate prediction results from many
      different sources and to project these prediction results into three dimensions.
      In addition, GLASS allows the comparison of selected parameters calculated for a
      model with the distribution observed in real protein structures, thus providing
      an easy way to test new methods for evaluating the likelihood of different
      structural models. GLASS can be considered as a "workbench" for structural
      predictions useful to both experimentalists and theoreticians.

PMID- 9533619
TI  - Nitric oxide myoglobin: crystal structure and analysis of ligand geometry.
AB  - The structure of the ferrous nitric oxide form of native sperm whale myoglobin
      has been determined by X-ray crystallography to 1.7 angstroms resolution. The
      nitric oxide ligand is bent with respect to the heme plane: the Fe-N-O angle is
      112 degrees. This angle is smaller than those observed in model compounds and in
      lupin leghemoglobin. The exact angle appears to be influenced by the strength of
      the proximal bond and hydrogen bonding interactions between the distal histidine
      and the bound ligand. Specifically, the N(epsilon) atom of histidine64 is located
      2.8 angstroms away from the nitrogen atom of the bound ligand, implying
      electrostatic stabilization of the FeNO complex. This interpretation is supported
      by mutagenesis studies. When histidine64 is replaced with apolar amino acids, the
      rate of nitric oxide dissociation from myoglobin increases tenfold.

PMID- 9533620
TI  - IMPALA: a simple restraint field to simulate the biological membrane in molecular
      structure studies.
AB  - The lipid bilayer is crucial for the folding of integral membrane proteins. This
      article presents an empirical method to account for water-lipid interfaces in the
      insertion of molecules interacting with bilayers. The interactions between the
      molecule and the bilayer are described by restraint functions designed to mimic
      the membrane effect. These functions are calculated for each atom and are
      proportional to the accessible surface of the latter. The membrane is described
      as a continuous medium whose properties are varying along the axis perpendicular
      to the bilayer plane. The insertion is analyzed by a Monte Carlo procedure
      applied to the restraint functions. The method was successfully applied to small
      alpha peptides of known configurations. It provides insights of the behaviors of
      the peptide dynamics that cannot be obtained with statistical approaches (e.g.,
      hydropathy analysis).

PMID- 9533621
TI  - A general method of domain closure is applied to phosphoglycerate kinase and the
      result compared with the crystal structure of a closed conformation of the
      enzyme.
AB  - The occurrence of large domain motions associated with the mechanism of action of
      many proteins is well established. We present a general method of predicting
      domain closure applicable to proteins containing domains separated by an apparent
      hinge. The method attempts to allow for natural directional bias within the
      closing protein by repeatedly applying a weak pulling force over a short distance
      between pairs of atoms chosen at random in the two domains in question.
      Appropriate parameters governing the pulling function were determined
      empirically. The method was applied to the bi-lobal protein PGK and a closed-form
      activated ternary complex generated for Bacillus stearothermophilus PGK. This
      model was compared with the recently determined crystal structure of closed-form
      Trypanosoma brucei PGK. The model predicts the correct hinge regions, although
      the magnitude of movement at one hinge point was overestimated, and provides a
      reasonable representation of the closed-form ternary complex.

PMID- 9533622
TI  - A fusion protein between serum amyloid A and staphylococcal nuclease--synthesis,
      purification, and structural studies.
AB  - We developed a recombinant DNA system to overexpress a fusion protein between the
      small, minimally soluble acute phase serum protein, serum amyloid A (SAA), and
      the bacterial enzyme staphylococcal nuclease (SN). This fusion protein is very
      soluble and is immunoreactive to polyclonal anti-SAA antibodies. Tryptophan
      fluorescence shows smooth denaturation curves for the fusion protein in
      guanidinium HCl or potassium thiocyanate. Fluorescence also indicates that only a
      single tryptophan residue (of the four present) is accessible to iodide quenching
      and, presumably, is exposed on the surface of the fusion protein. Circular
      dichroism (CD) shows a significant signal indicating alpha-helix, which can be
      attributed to the SAA portion of the molecule; these are the first CD spectral
      data available for SAA. pH titration shows persistence of helix domains for the
      fusion protein at pH 3.0, in contrast to the denaturation of SN under the same
      conditions. (The entire fusion protein shows a random coil pattern below pH 3.0.)
      By exploiting the structural and solubility properties of SN, this fusion protein
      has provided the first structural data about SAA-the precursor of the amyloid
      deposits in secondary amyloidosis. This fusion protein should be useful for
      further physical and physiologic studies of SAA.

PMID- 9533623
TI  - Improved protein free energy calculation by more accurate treatment of nonbonded
      energy: application to chymotrypsin inhibitor 2, V57A.
AB  - We developed a software package for improved free energy calculation, in which
      spherical solvent boundary potential, cell multipole method, and Nose-Hoover
      equation are employed. The performance of the developed software package is
      demonstrated in the case of valine to alanine mutation of the 57th residue in
      chymotrypsin inhibitor 2. By using this package, we obtained results
      quantitatively comparable to experimental results. By the free energy component
      analysis, it is shown that leucine 51, arginine 65, arginine 67, and
      phenylalanine 69 residues contribute significantly to the total free energy
      shift, deltadeltaG. Among them, contribution from the hydrophilic arginine 67
      residue, which is in close contact with the mutation site, is the largest.
      Structure around the mutation site is largely changed by the mutation. The
      structure change is caused mainly by two effects, hydrophobic interaction and
      short-range interaction along the sequence. Effects of Nose-Hoover algorithm and
      Kirkwood reaction field are also discussed.

PMID- 9533624
TI  - Surface-exposed phenylalanines in the RNP1/RNP2 motif stabilize the cold-shock
      protein CspB from Bacillus subtilis.
AB  - In the cold-shock protein CspB from Bacillus subtilis three exposed Phe residues
      (F15, F17, and F27) are essential for its function in binding to single-stranded
      nucleic acids. Usually, the hydrophobic Phe side chains are buried in folded
      proteins. We asked here whether the exposition of the essential Phe residues
      could be a cause for the very low conformational stability of CspB. Urea-induced
      and heat-induced equilibrium unfolding transitions were measured for three
      mutants of CspB, where Phe 15, Phe 17, and Phe 27 were individually replaced by
      alanine. Unexpectedly, all three mutations strongly destabilized CspB. The
      aromatic side chains of Phe 15, Phe 17, and Phe 27 in the active site are thus
      important for both binding to nucleic acids and conformational stability. There
      is no compromise between function and stability in the active site. Model
      calculations indicate that, although they are partially exposed to solvent, all
      three Phe residues nevertheless lose accessible surface upon folding, and this
      should favor the native state. A different result is obtained with the F38A
      variant. Phe 38 is hyperexposed in native CspB, and its substitution by Ala is in
      fact stabilizing.

PMID- 9533625
TI  - Electrostatic contributions to protein-protein binding affinities: application to
      Rap/Raf interaction.
AB  - The challenge of evaluating absolute binding free energies of protein-protein
      complexes is addressed using the scaled Protein Dipoles Langevin Dipoles (PDLD/S)
      model in combination with the Linear Response Approximation (LRA). This is done
      by taking the complex between Rap1A (Rap) and the p21ras binding domain of c-Raf
      (Raf-RBD) (Nassar et al., Nature 375:554-560, 1995) as a model system. Several
      formulations and different thermodynamic cycles are explored taking advantage of
      the LRA method and considering the protein reorganization during complex
      formation. The performance of different approximations is examined by comparing
      the calculated and observed absolute binding energies for the native complex and
      some of its mutants. The evaluation of the contributions of individual residues
      to the binding free energy, which is referred to here as group contributions is
      also examined. Special attention is paid to the role of the "dielectric
      constant," epsilon(in) which is in fact a scaling factor that represents the
      contributions that are treated implicitly. It is found that explicit
      consideration of protein relaxation is crucial for obtaining reasonable results
      with small values of epsilon(in), but it is also found that such a treatment of
      protein-protein interactions is very challenging and does not always give stable
      results. This indicates that more advanced explicit calculations should be based
      on experimentally determined structures of both the complex and the isolated
      proteins. Nevertheless, it is demonstrated that the qualitative trend of the
      effect of mutations can be reproduced by considering the effect of protein
      reorganization implicitly, using epsilon(in) approximately 25 for ionized
      residues and epsilon(in) approximately 4 for polar residues. Thus, it is
      concluded that an explicit treatment of solvent relaxation (which is common to
      current continuum models) does not provide sufficient compensation for turning
      off the charges of ionized residues on the interaction surface of the Raf-RBD/Rap
      complex. Representing the missing contribution by large epsilon(in) can, of
      course, reproduce the observed effect of ionized residues, but now the
      contribution of uncharged residues will be largely underestimated. Regardless of
      these conceptual problems, it is established that a very simple nonrelaxed
      approach, where the relaxation of both the protein and the solvent are considered
      implicitly, can provide an effective qualitative way for evaluating group
      contributions, using large and small values for epsilon(in) of ionized and
      neutral residues, respectively. As much as the actual system studied is concerned
      we find that more residues than generally assumed play a role in Raf-RBD/Rap
      interaction. This includes residues that are not located at the protein-protein
      interaction surface. These residues contribute to the binding energy through
      direct charge-charge interaction without leading to drastic structural changes.
      The overall contribution of the surface residues is quite significant since Raf
      and Rap are positively and negatively charged, respectively, and their charges
      are distributed along the interaction site between the two proteins.

PMID- 9533626
TI  - Oligopeptidase B: cloning and probing stability under nonequilibrium conditions.
AB  - Oligopeptidase B is a member of a new serine peptidase family, unrelated to the
      trypsin and subtilisin families. It is a potential processing enzyme of
      prokaryotes, being very specific for the basic amino acid pairs of polypeptides.
      An understanding of the kinetics of the enzyme requires the examination of its
      conformational stability under a variety of conditions. To this end, the enzyme
      was cloned from Escherichia coli HB101 by the PCR method, expressed with high
      yield in E. coli XL1-Blue, and purified essentially in two chromatographic steps.
      The denatured enzyme failed to refold, which precluded the calculation of free
      energy of stability, deltaG0. Therefore, the unfolding rates were measured to
      probe the stability against urea, pH, and heat. Denaturation processes were
      monitored by intrinsic fluorescence, circular dichroism, and activity
      measurements. A static method, intrinsic fluorescence vs. pH, was indicative of
      significant changes in the tertiary structure of the enzyme pH < 6 and pH > 8.5.
      The more sensitive dynamic methods, unfolding rates in urea and inactivation
      rates at high temperature, revealed increased flexibility in the protein
      structure between pH 6 and pH 7, where the static method did not show significant
      changes. Inactivation of the enzyme in the acidic pH range correlated with the
      results obtained with the static rather than with the dynamic method. Acid
      denaturation at pH 3 was markedly retarded by 1 M NaCl. Against heat inactivation
      the enzyme was also considerably protected in the presence of salt, and the
      higher enthalpy and entropy of activation suggested the importance of hydration
      in the stabilization. The kinetics of unfolding followed single-exponential decay
      under strongly denaturing conditions (high urea concentration or high
      temperature), but deviated from the apparently two-state mechanism at low urea
      concentrations and at slightly acidic pH. The results indicate that under harsher
      denaturing conditions there is a single rate-limiting step in unfolding, whereas
      under milder conditions partly unfolded intermediates are populated.

PMID- 9533627
TI  - Proteolysis as a probe of thermal unfolding of cytochrome c.
AB  - Recent hydrogen exchange experiments on native cytochrome c implicate a
      sequential unfolding pathway in contrast to a simple two-state process. We have
      studied the heat-induced unfolding of this protein by using spectroscopic
      measurements to detect changes in conformation and proteolytic enzyme digestion
      to identify regions of the protein that are labile. Several spectroscopic
      profiles were monitored: CD at 222 nm, a measurement of secondary structure
      change in the protein, the absorbance at 280 nm, involving the local environment
      of Trp 59, and absorbance at 420 nm, the Soret band of the heme. The apparent Tm
      values for these probes differ, consistent with an unfolding pathway containing
      intermediates. The limited digestion by proteinase K is consistent with
      population of an intermediate state in unfolding. We find a single strong region
      of cleavage at low temperature with retention of structure in each fragment.

PMID- 9533628
TI  - Crystallographic and spectroscopic characterization of a molecular hinge:
      conformational changes in bothropstoxin I, a dimeric Lys49-phospholipase A2
      homologue.
AB  - Bothropstoxin I (BthTX-I) from the venom of Bothrops jararacussu is a myotoxic
      phospholipase A2 (PLA2) homologue which, although catalytically inactive due to
      an Asp49-->Lys substitution, disrupts the integrity of lipid membranes by a Ca2+
      independent mechanism. The crystal structures of two dimeric forms of BthTX-I
      which diffract X-rays to resolutions of 3.1 and 2.1 angstroms have been
      determined. The monomers in both structures are related by an almost perfect
      twofold axis of rotation and the dimer interfaces are defined by contacts between
      the N-terminal alpha-helical regions and the tips of the beta-wings of partner
      monomers. Significant differences in the relative orientation of the monomers in
      the two crystal forms results in "open" and "closed" dimer conformations.
      Spectroscopic investigations of BthTX-I in solution have correlated these
      conformational differences with changes in the intrinsic fluorescence emission of
      the single tryptophan residues located at the dimer interface. The possible
      relevance of this structural transition in the Ca2+-independent membrane damaging
      activity is discussed.

PMID- 9533629
TI  - Thrombin-sensitive peptide linkers for biological signal-responsive drug release
      systems.
AB  - We have previously reported an elevation of thrombin-like activity in infected
      wound exudates. Therefore, using this enzymatic activity as a biological signal,
      a system which can release an antimicrobial drug at infected wounds was
      investigated. In this paper, we report thrombin-sensitive peptide linkers, the
      key component of this system. Starting from amino acid sequences of the cleavage
      site in fibrinogen, which is the substrate of thrombin, we synthesized some
      thrombin-sensitive peptide linkers. We constructed devices in which the thrombin
      sensitive peptide linker interconnected between polyvinyl alcohol hydrogel and
      gentamicin. The device was able to release gentamicin in response to thrombin.

PMID- 9533630
TI  - Inhibitory effect of cyclosporin A peptide on rat hepatocytes proliferation
      induced by mitogens.
AB  - Treatment of cultured rat hepatocytes with cyclosporin A (0.01-1 microM) for 24,
      48, or 72 h in the presence of insulin and epidermal growth factor induced an
      inhibition on cell proliferation in a time- and concentration-dependent manner,
      with an IC50 = 0.05 microM CsA corresponding to 48-h treatment. The inhibitory
      effect of CsA at < or = 0.1 microM doses for 48 h on [3H]thymidine uptake was
      reversed after withdrawal of the drug and subsequent addition of insulin plus EGF
      or serum; however, at 1 microM CsA the effect was irreversible and numerous
      bright small vesicles were observed. The molecular mechanism involved in CsA
      action in hepatocytes seems to be independent on cAMP and pertussis-toxin
      sensitive G proteins.

PMID- 9533631
TI  - Bovine mast cell tryptase inactivation: effect of temperature.
AB  - The thermal stability of bovine tryptase, a serine proteinase present in the
      bovine mast cell secretory granules, has been studied by circular dichroism and
      catalytic activity measurements. Bovine tryptase shows a peculiar dichroic
      negative band centered at 230 nm. The decrease of this band in a temperature
      dependent fashion represents a good marker to monitor the native conformation of
      the enzyme. Bovine tryptase inactivation has been followed in the temperature
      range between 10 degrees C and 80 degrees C, and reversibility of the process has
      been also studied. The results obtained show that the temperature dependent loss
      of activity and the conformational change, as monitored by circular dichroism,
      are both fully reversible between 10 degrees C and 40 degrees C, while only the
      CD change displays reversibility in going from 60 degrees C to 10 degrees C.
      Moreover, a functional analysis of the temperature-dependent enzymatic activity
      of bovine tryptase toward peptide substrates in the 10 degrees C - 40 degrees C
      range is reported and compared with the temperature dependence of the enzymatic
      activity of trypsin.

PMID- 9533632
TI  - Characterization of actions of Leucophaea tachykinin-related peptides (LemTRPs)
      and proctolin on cockroach hindgut contractions.
AB  - The nine Leucophaea Tachykinin-Related Peptides (LemTRP 1-9) isolated from the
      midgut and brain of the cockroach, Leucophaea maderae, all induced increases in
      spontaneous contractions of the L. maderae hindgut. Synthetic LemTRP 1 and 3-9,
      were equally potent in inducing contractions of the hindgut. More than seven of
      the nine C-terminal residues of the closely related locust peptide
      locustatachykinin I (LomTK I) are required for full activity of the peptide on
      the L. maderae hindgut. Proctolin, a well characterized myostimulatory
      neuropeptide, was shown to be more potent than LemTRPs. LemTRP 1 and proctolin
      did not have synergistic actions in potentiating the amplitude and tonus of
      contractions of the L. maderae hindgut. Several differences could be seen in
      actions of LemTRP 1 and proctolin. In contrast to proctolin, LemTRP 1 could not
      override the inhibitory action of 10(-9) M of the myoinhibitory peptide
      leucomyosuppressin. Spantide I, an antagonist of the mammalian tachykinin
      receptors, at a concentration of 5 microM, blocked the response to LemTRP 1, but
      not to proctolin. The competitive proctolin receptor antagonist [alpha-methyl-L
      tyrosine2]-proctolin blocked the action of both proctolin and LemTRP 1 when
      applied at 1 microM, whereas cycloproctolin had no antagonist action on either
      peptide. Verapamil, a blocker of voltage gated Ca2+-channels, and the less
      specific Ca2+-channel blocker Mn2+, abolished the action of LemTRP 1, but not of
      proctolin. The results obtained indicate that LemTRPs act on receptors distinct
      from those of proctolin. Double label immunocytochemistry revealed that all LomTK
      like immunoreactive fibers impinge on the proctolinergic fibers in the hindgut.
      This finding and the inhibitory actions of Ca2+-channel blockers on TRP responses
      and of the proctolin receptor antagonist on both peptides, may suggest that the
      LemTRP receptors are not on the hindgut muscle fibers but on the terminals of the
      proctolinergic neurons. Thus, LemTRPs may induce release of proctolin on the
      hindgut. An alternative is that LemTRPs act by mechanisms clearly distinct from
      those of proctolin.

PMID- 9533633
TI  - The effects of SchistoFLRFamide on contractions of locust midgut.
AB  - The midgut of insects has recently been shown to contain numerous endocrine-like
      cells and the midgut is now considered one of the largest endocrine organs in the
      insect. Using immunohistochemistry, radioimmunoassay, and muscle bioassay
      techniques, the midgut of the adult locust, Locusta migratoria, has been
      investigated for the distribution and possible function of FMRFamide-related
      peptides contained within these endocrine-like cells and innervation. Endocrine
      like cells containing RFamide-like immunoreactivity were observed to be unequally
      distributed throughout the midgut. RFamide-like immunoreactivity was also seen in
      the ingluvial ganglion and in the nerves projecting posteriorly to the midgut.
      These axonal tracts resulted in extensive arborizations over the posterior midgut
      which were RFamide-like immunoreactive. Radioimmunoassay indicated larger amounts
      of FMRFamide equivalents in female locust midgut as compared to males with an
      unequal distribution of FMRFamide-like immunoreactivity in the gastric caeca and
      in the anterior and posterior parts of the midgut. Circular muscle contraction of
      the midgut was monitored using a ring-type preparation. Structure/activity
      studies have shown that the only FMRFamide-related peptides tested that alter
      circular muscle contraction of the midgut are those that belong to the subfamily
      referred to as myosuppressins. SchistoFLRFamide, leucomyosuppressin, and
      ManducaFLRFamide were each capable of lowering basal tonus and inhibiting
      spontaneous and proctolin-induced contractions of midgut muscle. Further
      structure/activity studies indicated that HVFLRFamide is the minimum sequence
      required to achieve inhibition comparable to the parent compound. This work
      suggests that a possible function for the FMRFamide-related peptides contained
      within the endocrine cells and innervation of the midgut of the locust may be in
      modulating midgut contraction and thereby playing a role in digestion.

PMID- 9533634
TI  - The influence of neuropeptides on Malpighian tubule writhing and its significance
      for excretion.
AB  - Diuretic peptides (locustakinin and Locusta-DH) increase the spontaneous
      contractile activity of visceral muscle fibers associated with Malpighian tubules
      from the migratory locust (Locusta migratoria) at concentrations that increase
      urine production. Muscle activity is shown to assist the flow of material in the
      tubule lumen, but is not essential for diuresis. Tubule writhing also serves to
      reduce unstirred layers (USLs) at the basolateral surface of the epithelium and
      thereby facilitates the excretion of solutes entering the lumen by passive
      diffusion.

PMID- 9533635
TI  - Analogs of Manduca adipokinetic hormone tested in a bioassay and in a receptor
      binding assay.
AB  - Single amino acid replacement analogs of Manduca adipokinetic hormone (M-AKH)
      pGlu-Leu-Thr-Phe-Thr-Ser-Ser-Trp-GlyNH2 were tested for activity in bioassays as
      well as receptor binding assays. Amino acids were replaced by Ala and by D
      analogs. In addition an extended M-AKH and analogs containing photo affinity
      labels were tested. All analogs had reduced activity. All the peptides which had
      enough activity to allow a full dose response curve reached the same maximal
      activity as native M-AKH. The use of analogs, in which L-Phe4 was replaced by Ala
      or by D-Phe and of L-Thr3 replaced by D-Thr, as competitors led to improved
      binding of M-AKH in our competitive receptor binding assay. In the bioassay an
      inactive concentration of Ala4 M-AKH increased the activity of a half optimal
      concentration of native M-AKH.

PMID- 9533636
TI  - Identification and characterization of a myomodulin-like peptide in the leech.
AB  - A novel myomodulin-like peptide, GMGALRLamide, has been purified and sequenced
      from extracts of 1000 medicinal leech nerve cords. Synthetic leech myomodulin
      like peptide blocked the specific staining pattern of leech ganglia by the
      antiserum against Aplysia myomodulin A PMGMLRLamide. Moreover, the synthetic
      leech myomodulin-like peptide GMGALRLamide showed identical neuronal modulation
      effect on the giant leech Retzius cell compare to that by the synthetic Aplysia
      myomodulin A PMGMLRLamide.

PMID- 9533637
TI  - Bovine milk inhibits proteolytic degradation of epidermal growth factor in human
      gastric and duodenal lumen.
AB  - Degradation of epidermal growth factor (EGF) in human gastric and duodenal lumen
      was analyzed by incubating 125I-labeled or unlabeled human recombinant EGF with
      human gastric or duodenal luminal fluids in vitro. Degradation of EGF was
      assessed by measuring the generation of acid soluble radioactivity or by reversed
      phase high-performance liquid chromatography (HPLC). Incubation with gastric
      luminal fluids resulted in a time- and dose-dependent degradation of labeled and
      unlabeled EGF at pH 2.5 but not at pH 7.5. Duodenal luminal fluids, on the other
      hand, degraded EGF at pH 7.5 but not at pH 2.5. The rate of degradation of
      unlabeled EGF in gastric luminal fluids was nearly 12-fold higher than the rate
      of degradation of labeled EGF, whereas only a slight difference in rates of
      degradation of labeled and unlabeled EGF was observed in duodenal luminal fluids.
      High-performance liquid chromatography analysis detected three major degradation
      products that eluted with retention time of 17.5 min, 20.0 min, and 22.5 min that
      was associated with a reduction of intact EGF (retention time 23.5 min). Defatted
      and decaseinated supernatant of bovine milk effectively inhibited the degradation
      of EGF in both gastric and duodenal luminal fluids. Dietary derived protease
      inhibitors, such as soya bean trypsin inhibitor, lima bean trypsin inhibitor, egg
      white protease inhibitor, and Bowman-Birk protease inhibitor prevented EGF
      degradation in duodenal luminal fluids but failed to inhibit EGF degradation in
      gastric luminal fluids. These results suggest that bovine milk may contain
      specific inhibitors that protect EGF from proteolytic degradation in human
      gastric lumen.

PMID- 9533638
TI  - Inhibitory effect of serotonin on feeding behavior in goldfish: involvement of
      CRF.
AB  - The possible action of 5-HT on feeding behavior in goldfish has been studied.
      Food intake was significantly reduced by intracerebroventricular (ICV) injection
      of serotonin (5-HT, 10 microg) at 2 h postinjection. After peripheral
      (intraperitoneal) administration of 5-HT (1 and 10 microg/g bw), no significant
      modifications in food intake were detected. Thus, it can be concluded that there
      is a central anoretic action of 5-HT in teleost fish. Taking in mind the
      inhibitory effect of corticotropin releasing factor (CRF) on feeding in teleosts
      and the interactions between 5-HT and CRF described in mammals, we investigated
      the possible involvement of CRF as mediator of the 5-HT anoretic action in
      goldfish. The ICV pretreatment with alpha-Helical CRF[9-41](20 microg) partially
      blocked the inhibitory effect of 5-HT on food consumption in goldfish. These
      results show that CRF mediates, at least in part, the 5-HT-induced feeding
      inhibition in goldfish. On the other hand, the alterations in hypothalamic
      indoleamines content evoked by ICV treatments would suggest that the activation
      of CRF neurons by 5-HT appears to inhibit hypothalamic serotoninergic
      transmission, supporting the intermediate role of this neuropeptide in the
      central anoretic effect of 5-HT in goldfish.

PMID- 9533639
TI  - Effect of urocortin and its interaction with adrenocorticotropin (ACTH)
      secretagogues on ACTH release.
AB  - We examined the effect of urocortin (Ucn) on the adrenocorticotropin (ACTH)
      release from cultured rat anterior pituitary cells and AtT 20 cells. Synthetic
      rat (r)Ucn was not soluble in 0.1 N HCl but soluble in alkaline solvents with
      diminished corticotropin-releasing activity. rUcn dissolved in 0.1 M sodium
      phosphate buffer as a stock solution maintained its bioactivity and had the equal
      corticotropin-releasing activity with rat/human corticotropin-releasing factor
      (r/hCRF). rUcn stimulated the adrenocorticotropin release via CRF-receptors
      accompanied by the additive effect with r/hCRF, the synergistic effect with
      arginine vasopressin and the dose-dependent inhibition of a potent CRF-receptor
      antagonist.

PMID- 9533640
TI  - Effects of cholecystokinin-receptor agonists on cortical 5-HT release in guinea
      pigs on the X-maze.
AB  - Exposure of guinea pigs to the elevated plus maze (X-maze), an animal model of
      anxiety, causes an increase of extracellular serotonin (5-HT) in the lateral
      prefrontal cortex monitored by microdialysis. The neuropeptide cholecystokinin
      (CCK) plays a role in the modulation of anxiety. To compare the roles of CCK
      receptors, the effects of the CCK-A receptor agonist A-71378, the CCK-A/B
      receptor agonist CCK-8S and the CCK-B receptor agonist BOC-CCK-4 on anxiety
      related behavior and the 5-HT release in the prefrontal cortex were determined.
      None of the drugs changed the behavior of the guinea pigs and the cortical 5-HT
      release under resting conditions in the familiar home cage. A-71378 and CCK-8S
      had no effect on the behavior on exposure to the X-maze whereas BOC-CCK-4 induced
      an 'anxious' behavior. The results suggest that 'anxious' behavior induced by CCK
      is associated with selective CCK-B receptor stimulation. A-71378 inhibited the
      rise in 5-HT on exposure to the X-maze. CCK-8S had no effect and the anxiogenic
      BOC-CCK-4 potentiated the rise in 5-HT on the X-maze. Both CCK receptors mediate
      changes in 5-HT release under aversive conditions, but not in a resting state.
      The results suggest a receptor subtype-specific influence of CCK on behavior and
      5-HT activity under aversive conditions.

PMID- 9533641
TI  - Neuropeptide Y and somatostatin in the anterior piriform cortex alter intake of
      amino acid-deficient diets.
AB  - Neuropeptides affect food intake via peripheral and brainstem mechanisms, but
      their roles in mediating feeding via the cerebral cortex have received little
      attention. The anterior piriform cortex (APC) appears to play a critical role in
      neuroperception of deficiencies of essential amino acids (AA) and the anorectic
      response to such deficiencies. The neural circuitry underlying the role of this
      paleocortex in these events is not understood. We have shown that neurons
      containing neuropeptide Y (NPY) and somatostatin (SOM) are cytoarchitecturally in
      positions to relate synaptically to the neurons of the APC which may mediate
      responses to AA. Thus, we hypothesized that NPY and SOM administered
      intracortically to the APC would directly affect food intake in a threonine
      imbalanced model. We determined that NPY at 1-1.5 nmol decreased intake of the AA
      deficient diet for 3 h, with a cumulative effect that extended through 6 h. SOM
      had a dual effect; at 1 pmol it increased intake of the AA-deficient diet for 3
      h; at 2 nmol, SOM decreased intake of the AA-deficient diet for over 9 h, with a
      cumulative effect that persisted through 12 h. In the first 3 h, intake of
      animals receiving 1 pmol of SOM differed significantly from those receiving 2
      nmol. These results suggest that NPY and SOM affect the cortical circuitry
      responsible for recognition of deficiencies in nutritionally essential AA, and
      that the timing of the cortical responses to the peptides may be related to the
      time course of the anorectic responses.

PMID- 9533642
TI  - The neuropeptide Y Y1 antagonist, 1229U91, a potent agonist for the human
      pancreatic polypeptide-preferring (NPY Y4) receptor.
AB  - Recently, a novel high-affinity peptide antagonist, 1229U91, was published as a
      selective neuropeptide Y Y1 antagonist. The selectivity of 1229U91 was evaluated
      in the human NPY Y1 receptor containing cell line, SK-N-MC, and cells containing
      the cloned human NPY Y2, the pancreatic polypeptide-preferring (NPY Y4), and the
      NPY Y5 receptors. 1229U91 potently displaced [125I]-peptide YY (PYY) binding to
      human NPY Y1 receptors (IC50 = 0.245+/-0.004 nM, n = 4). but displayed little
      affinity for the human NPY Y2 and Y5 receptors (IC50 > 1000 nM). Interestingly,
      1229U91 displaced [125I]-PYY with even greater affinity at the human NPY Y4
      receptor (IC50 = 0.081+/-0.009 nM, n = 4). Using a cyclic AMP accumulation assay,
      1229U91 blocked NPY inhibition of forskolin-induced adenylate cyclase activity in
      NPY Y1 receptor containing SK-N-MC cells. In the human NPY Y4 receptor expressing
      cell line, 1229U91 did not block pancreatic polypeptide (PP) inhibition of
      forskolin stimulated adenylate cyclase. However, in the absence of PP, 1229U91
      was able to inhibit forskolin stimulated cyclic AMP accumulation (IC50 = 7.16+/
      2.8 nM, n = 4). We conclude that 1229U91 binds non-selectively with high affinity
      to both human NPY Y1 and Y4 receptors. Furthermore, 1229U91 displays antagonist
      activity at the NPY Y1 receptor, while having agonist activity at the NPY Y4
      receptor.

PMID- 9533643
TI  - Effects of high dose octreotide on retrograde bile salt-induced pancreatitis in
      rats.
AB  - The effects of somatostatin and octreotide (a long acting somatostatin analogue)
      in acute pancreatitis are inconclusive. This study examined the prophylactic and
      therapeutic effects of different doses of octreotide on retrograde sodium
      taurodeoxycholate-induced acute necrotizing pancreatitis in rats. The rats were
      divided into 4 groups receiving subcutaneous injection of saline, octreotide 10
      microg/kg, 20 microg/kg at 0, 8 and 16 h and octreotide 20 microg/kg at 5, 13 and
      21 h, separately. The serum levels of amylase and lipase, pancreatic
      histopathology, mortality and hemodynamics were examined. Octreotide
      significantly reduced serum levels of amylase and lipase at 12 h and the degree
      of pancreatic edema, necrosis and hemorrhage at 18-24 h as compared to the
      control group. Prophylactic octreotide 10 microg/kg significantly decreased the
      24-h mortality from 100% to 44.4% (p < 0.05). The 24-h mortality further reduced
      to 12.5% and 10% with prophylactic and therapeutic octreotide 20 microg/kg,
      respectively. The decrease of mean arterial pressure at 12 h was significantly
      lower in octreotide groups than in the control group. We conclude that octreotide
      improves pancreatic histopathology and survival in acute necrotizing pancreatitis
      in rats.

PMID- 9533644
TI  - Role of different bombesin receptor subtypes mediating contractile activity in
      cat upper gastrointestinal tract.
AB  - Mammalian bombesin-like peptides, gastrin-releasing peptide (GRP) and neuromedin
      B (NMB) are known to increase the motility of different segments in the gut. The
      present study was carried out to identify the bombesin receptor subtypes
      mediating the contractions induced by exogenous bombesin-like peptides in muscle
      strips isolated from cat esophagus, fundus, and duodenum. Both GRP-10 and NMB
      evoked concentration-dependent contractions in circular strips of esophagus and
      fundus and in longitudinal strips of the duodenum. These contractions were
      tetrodotoxin- and atropine-resistant. The potency of NMB in esophageal strips was
      33 times higher than that of GRP-10. The NMB-preferring receptor antagonists D
      Nal-Cys-Tyr-D-Trp-Lys-Val-Cys-Nal-NH2 (SSocta) and D-Nal-cyclo[Cys-Tyr-D-Trp-Orn
      Val-Cys]-Nal-NH2 (BIM-23127) shifted the NMB and GRP concentration-response
      curves to the right, while the GRP-preferring receptor antagonist [D
      Phe6]Bombesin(6-13)-methyl-ester (BME) did not affect the response to the
      peptides. Isolated muscle strips from the cat fundus and duodenum showed a higher
      sensitivity to GRP-10 than to NMB. In both segments, BME shifted the GRP-10 and
      NMB concentration-response curves to the right, while SSocta had no effect. The
      antagonism of BME was competitive on duodenal but not competitive on fundic
      muscle. We conclude that the direct myogenic action of GRP-10 and NMB in the
      esophagus is mediated mainly via NMB-preferring receptors, while GRP-preferring
      receptors are responsible for the contractile responses to bombesin-like peptides
      in feline fundus and duodenum. Our data suggest that the GRP receptor population
      located on fundic muscle might be nonhomogeneous.

PMID- 9533645
TI  - Changes in the microstructure of feeding after administration of enterostatin
      into the paraventricular nucleus and the amygdala.
AB  - The effects of enterostatin (ENT) injected into the paraventricular nucleus (PVN)
      and the amygdala (AMYG) on the microstructure of feeding was studied by using an
      automated feeding apparatus. In rats adapted to a 6-h meal feeding regime, ENT
      reduced the size and duration of the first meal after injection in both the PVN
      and the AMYG. Similar effects were observed when ENT was given at the beginning
      of the dark cycle in rats fed ad libitum although the onset of feeding was also
      delayed in this situation. The number of meals and the size of subsequent meals
      was unaffected by ENT but the eating rate within the first meal was reduced after
      ENT injection into the AMYG of meal-fed rats. Enterostatin injected into the AMYG
      at a dose that suppressed feeding did not produce a conditioned taste aversion.
      ENT given centrally therefore appears to reduce food intake by delaying the
      initiation of feeding and/or advancing meal termination suggesting that it
      affects both appetite and satiation mechanisms.

PMID- 9533646
TI  - Interactions of cocaine with morphine, U-50,488H and [D-Pen2, D-Pen5]enkaphalin.
AB  - The effects of acute and chronic administration of cocaine on the antinociception
      and tolerance to the antinociceptive actions of mu-(morphine), kappa-(U-50,488H),
      and delta-([D-Pen2,D-Pen5]enkephalin; DPDPE), opioid receptor agonists were
      determined in male Swiss-Webster mice. Intraperitoneal injection of 40 mg/kg of
      cocaine by itself produced weak antinociceptive response as measured by the tail
      fick test but the lower doses were ineffective. Administration of morphine (10
      mg/kg, SC), U-50,488H (25 mg/kg, IP) or DPDPE (10 microg/mouse, ICV) produced
      antinociception in mice. Cocaine (20 mg/kg) potentiated the antinociceptive
      action of morphine and DPDPE but had no effect on U-50,488H-induced
      antinociception. Administration of morphine (20 mg/kg, SC), U-50,488H (25 mg/kg,
      IP) or DPDPE (20 microg/mouse, ICV) twice a day for 4 days resulted in the
      development of tolerance to their antinociceptive actions. Tolerance to the
      antinociceptive actions of morphine and U-50,488H was inhibited by concurrent
      treatment with 20 or 40 mg/kg doses of cocaine; however, tolerance to the
      antinociceptive action of DPDPE was not modified by cocaine. It is concluded that
      cocaine selectively potentiates the antinociceptive action of mu- and delta- but
      not of the kappa-opioid receptor agonist. On the other hand, cocaine inhibits the
      development of tolerance to the antinociceptive actions of mu- and kappa- but not
      of delta-opioid receptor agonists in mice.

PMID- 9533647
TI  - Kinin B2 and B1 receptor-mediated vasoactive effects in rabbit synovium.
AB  - Blood flow in response to bradykinin (BK, B2 receptor agonist) and desArg9 BK (B1
      receptor agonist) was measured by laser Doppler flowmetry, as a reversal of
      noradrenaline (50 nmol)-induced decreased blood flow, in the synovium of the
      anaesthetised rabbit. Either a pretreatment (-6 h) of the cytokines IL-1beta (10
      pmol) plus TNFalpha (10 pmol) or saline was injected intra-articularly. BK
      increased blood flow irrespective of pretreatment, whereas desArg9BK increased
      blood flow only in the cytokine-pretreated joints. The B2 antagonist HOE 140
      reversed (p < 0.01) only the BK responses, and the B1 antagonist desArg9Leu8BK
      only reversed desArg9BK responses (p < 0.001). A nitric oxide synthase inhibitor,
      (L-NAME, 10 micromol kg(-1)), reversed the effects of the kinins (p < 0.05), but
      not sodium nitroprusside-stimulated responses. The results suggest that the B2
      receptor is constitutively expressed and that the B1 receptor can mediate
      responses in inflamed tissues. The results, in addition, indicate that the
      responses, mediated via both receptors, are nitric oxide-dependent.

PMID- 9533648
TI  - Calcitonin gene-related peptide (CGRP), but not tachykinins, causes relaxation of
      small arteries from the rainbow trout gut.
AB  - Possible vasoactive effects on small diameter arteries from the rainbow trout gut
      of calcitonin gene-related peptide (CGRP-chicken) and different fish tachykinins;
      substance P (SP-trout), neurokinin A (NKA-trout), scyliorhinin I and II (SCY I
      and SCY II-dogfish), were investigated. CGRP relaxed precontracted arteries with
      a pD2 value of 8.3+/-0.2. Relaxation to CGRP 10(-8) M was reduced by 86.4+/-5.2%
      by the CGRP-1 receptor antagonist CGRP8-37 (10(-6) M), but unaffected by NG-nitro
      L-arginine (10(-4) M), indomethacin (10(-6) M) and by removal of the endothelium,
      suggesting no involvement of nitric oxide, prostaglandins or endothelium-derived
      factors. A low number of CGRP immunoreactive fibers were present in the arterial
      wall. The tachykinins (10(-12)-10(-6) M) occasionally contracted the relaxed
      vessel. No synergistic action of SP on the CGRP-induced response was found. A
      dense plexus of tachykinin-containing fibers without coexisting CGRP innervated
      the arterial wall. Tachykinins or CGRP had no effect on small diameter veins, and
      no such immunoreactivity was found in these vessels. In conclusion, CGRP- and
      tachykinin-containing fibers innervate trout gut arteries. CGRP probably is
      vasodilatory, while the function of the tachykinin fibers is unknown.

PMID- 9533649
TI  - (Arg15, Arg21) VIP: evaluation of biological activity and localization to breast
      cancer tumors.
AB  - VIP analogs, which contain a single lysine amino acid, were synthesized and
      evaluated using breast cancer cells. (Arg15, Arg20) VIP, (Argl5, Arg21) VIP, and
      (Arg20, Arg21) VIP inhibited 125I-VIP binding to T47D cells with high affinity
      (IC50 values of 1.2, 1.0, and 0.8 nM, respectively). The VIP analogs elevated
      cAMP in T47D cells with ED50 values ranging from 0.1-1 nM. Because (Arg15, Arg21)
      VIP was the most potent at elevating cAMP, it was characterized further. (Arg15,
      Arg21) VIP transiently increased c-fos gene expression in breast cancer cells. N
      Succinimidyl-4-18F (fluoromethly) benzoate was prepared in one chemical step from
      N-succinimidyl-4-(4-nitrobenzenesulfonyl)oxomethyl)benzoate by adding 18F in
      acetone at room temperature. This prosthetic group was then reacted with (Arg15,
      Arg21) VIP ((RR) VIP). (18F-RR) VIP bound with high affinity to T47D cells and
      was rapidly internalized. (18F-RR) VIP was injected intravenously into nude mice
      bearing breast cancer xenografts and after 4 h, the density of (18F-RR) VIP was
      elevated in the tumors relative to normal organs. These data suggest that VIP
      receptors may be used to localize breast cancer tumors.

PMID- 9533650
TI  - A novel long-acting VIP analog in the guinea pig trachea in vitro.
AB  - The relaxant effect of a novel VIP analog, [Arg15,20,21Leu17]-VIP-Gly-Lys-Arg-NH2
      was compared with that of the original VIP in the same guinea pig trachea
      precontracted by carbachol in vitro. The VIP analog caused significantly and
      concentration-dependent relaxation similarly to the original VIP. In contrast to
      the original VIP, the VIP analog demonstrated a slow onset and offset of action,
      with more than 90% of its maximum relaxation remaining 6 h after administration.
      Peptidase inhibition by captopril and phosphoramidon increased the relaxant
      effect and duration of action for original VIP but not for the VIP analog.

PMID- 9533651
TI  - Permeation and pathways of human calcitonin (hCT) across excised bovine nasal
      mucosa.
AB  - In vitro permeation of human calcitonin (hCT), salmon calcitonin (sCT), and the
      somatostatin analog octreotide (SMS) through excised bovine nasal mucosa was
      studied applying donor/receiver experiments and confocal laser scanning
      microscopy. Permeabilities of gonadorelin, buserelin, Hoe013, and of thymopoietin
      fragments TP5 and TP4 were also included. Apparent permeability coefficients
      (Peff) ranged between 4 x 10(-5) (SMS) and 1.7 x 10(-5) cm s(-1) (TP4). Such Peff
      are typical for leaky-type airway epithelia. The order of permeabilities was: SMS
      >> hCT, sCT > buserelin, Hoe013 >> TP5 > TP4, LHRH. The relatively high
      permeability of hCT and sCT contrasted to their high molecular weight. At 37
      degrees C, the permeability of hCT from mucosal to serosal (m-to-s) was found two
      fold higher (p < 0.05) than from serosal to mucosal (s-to-m). Controls using 3H
      mannitol showed equal permeabilities in both directions. At 4 degrees C,
      permeation of hCT was reduced but equal in both directions (m-to-s and s-to-m).
      As evaluated by confocal laser scanning microscopy, uptake studies with FITC-18
      hCT revealed intracellular fluorescence in the epithelial cells, at 10 min/10
      microM exposure in the form of fluorescent vesicles. By combination of these
      findings, an endocytotic pathway is suggested to contribute to the transport of
      hCT through nasal epithelium.

PMID- 9533652
TI  - Xenin--a review.
AB  - Xenin, a 25 amino acid peptide, has been identified in human gastric mucosa in
      the search for a counterpart to the amphibian octapeptide xenopsin. Xenin is
      structurally related also to the hypothalamic and ileal peptide neurotensin and
      is, therefore, a member of the xenopsin/neurotensin/xenin peptide family. The
      biological activities of these peptides are similar: Xenin has been shown to
      inhibit pentagastrin-stimulated secretion of acid, to induce exocrine pancreatic
      secretion and to affect small and large intestinal motility. In the gut, xenin
      interacts with the neurotensin receptor. Radioimmunoassay and chromatography of
      postprandial plasma in humans indicate the release of xenin into the circulation.
      The identification of a 35-amino acid precursor peptide of xenin - proxenin, and
      a review of the Gen-bank revealed that xenin represents the N terminus of a
      cytosolic coat protein (alpha-COP) from which xenin can be cleaved by aspartic
      proteinases such as pepsin and cathepsin E. The physiological role of the peptide
      xenin is not known.

PMID- 9533654
TI  - Spontaneous autoimmune disease in (NZB x NZW)F1 mice is ameliorated by treatment
      with methimazole.
AB  - (NZB x NZW)F1 mice spontaneously develop with age an autoimmune disease that
      resembles the human disease, systemic lupus erythematosus (SLE). The present
      study demonstrates that methimazole (MMI), an agent used in the treatment of
      autoimmune thyroid disease, is effective in mitigating the development of this
      SLE-like autoimmune disease in (NZB x NZW)F1 mice. MMI significantly reduces the
      incidence and severity of proteinuria and deposition of immune complexes in the
      kidney. Previous studies have demonstrated that development of an experimentally
      induced SLE, which was prevented by MMI treatment, depended on the expression of
      MHC class I molecules. We now report that class I levels on both T cells and B
      cells from old (NZB x NZW)F1 MHC class I are markedly elevated relative to those
      from young F1 mice. Furthermore, treatment of (NZB x NZW)F1 mice with MMI reduced
      MHC class I expression on their PBL concomitant with amelioration of disease,
      raising the possibility that class I molecules may play a role in the generation
      of spontaneous autoimmune disease in these mice.

PMID- 9533653
TI  - Genetic defects in Chediak-Higashi syndrome and the beige mouse.
AB  - Chediak-Higashi syndrome (CHS) is a rare, autosomal recessive, multisystem
      disorder in which severe immune deficits are accompanied by abnormalities of
      pigmentation, blood clotting, and neurologic function. There is no specific
      treatment, and without bone marrow transplantation, most patients succumb to
      frequent bacterial infections or to a lymphoproliferative syndrome that appears
      to result principally from lack of natural killer cell function. Disorders
      similar to human CHS occur in many mammalian species, the most important being
      the beige mouse, long considered a likely homologue of human CHS. This
      supposition has recently been confirmed by the mapping, cloning, and mutation
      analysis of the homologous human CHS1 and mouse beige genes. Identification of
      the human CHS1 gene, and the availability of a ready mouse model for human CHS,
      will likely facilitate investigation of the disease pathophysiology and the
      development of novel and specific treatments for the disorder.

PMID- 9533655
TI  - Setaria digitata adult 14- to 20-kDa antigens induce differential Th1/Th2
      cytokine responses in the lymphocytes of endemic normals and asymptomatic
      microfilariae carriers in bancroftian filariasis.
AB  - High titers of parasite antigen-specific IgG4 antibodies have been found to be
      circulating in the peripheral blood of chronic patients, asymptomatic
      microfilariae carriers, and endemic normals in bancroftian filariasis. But in
      contrast to this, the titers of antigen-specific IgG1, IgG2, and IgG3 isotype
      antibodies are much lower. Using soluble antigens of adult Setaria digitata, a
      cattle parasite which shows strong antigenic reactivity with filaria sera, we
      have identified, by immunoblot, 14- to 20-kDa antigens which are recognized only
      by the IgG4 isotype antibodies present in the sera of asymptomatic microfilariae
      carriers. These 14- to 20-kDa antigens, after fractionation by SDS-PAGE and
      transfer to nitrocellulose paper, when solubilized and tested in vitro, induced
      secretion of a higher quantity of IFN-gamma and a lower quantity of IL-4, IL-5,
      and IL-10 (differential Th1 and Th2 response) in the lymphocytes of endemic
      normals in comparison to what they induced in the lymphocytes of asymptomatic
      microfilariae carriers.

PMID- 9533656
TI  - Induction of HIV-1 replication by type 1-like cytokines, interleukin (IL)-12 and
      IL-15: effect on viral transcriptional activation, cellular proliferation, and
      endogenous cytokine production.
AB  - Cytokine dysregulation is evident in HIV-1 infection and it may play an important
      role in HIV-1 pathogenesis. Administration of T helper cytokines potentially may
      restore the functional abnormalities to the HIV-1 immune response. Type 1-like
      cytokines, IL-2, IL-12, and IL-15, are candidates for immune-based therapy for
      HIV. Given their potential therapeutic use, we determined the effects of IL-2, IL
      12, and IL-15 on HIV-1 replication in both primary blood mononuclear cells (PBMC)
      and the T-cell line, Kit 225-K6. We demonstrate that both IL-2 and IL-12 induce a
      similar level of HIV-1 replication (9- and 11-fold, respectively) in mitogen
      stimulated PBMC. The effect of IL-2 plateaued by day 6, while that of IL-12
      continued to increase HIV-1 expression. IL-15 induced a 2.5-fold increase in HIV
      1 expression that remained at the same level through day 6. In Kit 225-K6, an IL
      2-dependent T cell line, IL-12 and IL-15 enhanced HIV-1 replication by 5- and 3.5
      fold over IL-2-treated cultures, respectively. IL-2-, IL-12-, and IL-15-mediated
      induction of HIV was independent of direct HIV-1 LTR activation, since none of
      the cytokines induced LTR activity from transfected reporter gene constructs. The
      cytokine-mediated induction of HIV-1 expression was also independent of cellular
      proliferation. In PBMC, the IL-12-mediated effect was partially mediated by
      endogenous cytokine production of IL-1beta and IL-7, whereas in Kit 225-K6,
      TNFalpha, INFgamma, IL-1beta, and IL-7 did not contribute significantly to the IL
      12-mediated effect. IL-15 effect on HIV-1 in PBMC was independent of endogenous
      cytokine production. However, in Kit 225-K6, neutralizing antibodies to IL-7 had
      a significant effect on HIV-1 expression. These data suggest that IL-2, IL-12,
      and IL-15 increase HIV-1 replication predominantly through a posttranscriptional
      mechanism that may be enhanced by endogenous cytokine production.

PMID- 9533657
TI  - Clinical significance of natural killing activity in patients with advanced
      lymphoma.
AB  - Using a newly described analysis of natural killing activity employing an
      "individual effector/target cell ratio" according to the number of effector cells
      in blood, we recently determined that patients with spontaneous lymphoma
      regression had elevated natural killing activity prior to regression. To clarify
      the clinical significance of natural killing activity in patients with advanced
      lymphoma, a prospective study was performed at a single institution in 43
      untreated patients. Survival was analyzed to detect prognostic variables. Among
      factors chosen initially by univariate analyses, multivariate analysis selected
      three prognostic factors: chemotherapy response (P < 0.0001), low-grade lymphoma
      (P = 0.0005), and natural killing activity (P = 0.0052). Within the chemotherapy
      response, natural killing activity was a unique correlative factor (P < 0.0001)
      selected by a multivariate regression analysis using forward selection method. In
      patients with advanced lymphoma, natural killing activity is a valuable
      prognostic factor and may also predict the response to chemotherapy.

PMID- 9533658
TI  - A panel set for epitope analysis of myeloperoxidase (MPO)-specific antineutrophil
      cytoplasmic antibody MPO-ANCA using recombinant hexamer histidine-tagged MPO
      deletion mutants.
AB  - A major target protein of antineutrophil cytoplasmic antibody with a perinuclear
      staining pattern (P-ANCA) has been identified as myeloperoxidase (MPO).
      Recombinant deletion mutants of MPO, eight fragments of the heavy-chain subunit,
      and two fragments of the light chain subunit were expressed in E. coli using a
      pQE expression vector. The recombinant hexamer histidine-tagged fragments were
      partially purified as the denatured proteins on a Ni2+-charged nitrirotriacetic
      acid column. The recombinant fragments were reacted with a rabbit polyclonal
      antibody to human MPO in Western blotting. In addition, the reactivities of the
      proteins with MPO-ANCA-positive sera of four patients with renal diseases were
      examined by Western blotting. The profile of the reactivity showed that different
      sera recognized different sets of fragments of the heavy chain, whereas no serum
      reacted with the fragments of the light chain. These results indicate that the
      sera of patients with MPO-ANCA-positive diseases showed varied reactivities with
      the different fragments. Furthermore, an ELISA system using a set of the
      fragments completely purified by Sephacryl S-200HR column chromatography was
      established. The panel set is useful for subclassification of MPO-ANCA-related
      diseases.

PMID- 9533661
TI  - Migraine researchers--from Wolff to Humphrey.

PMID- 9533659
TI  - pANCA represents a cross-reactivity to enteric bacterial antigens.
AB  - pANCA (perinuclear antineutrophil cytoplasmic antibodies) occur at a high
      frequency in patients with ulcerative colitis. The purpose of this study was to
      investigate the frequency of pANCA in different mouse models of colitis and to
      determine whether there is any cross-reactivity of pANCA with bacterial antigens.
      Sera from 146 colitic mice and controls and from 30 patients with ulcerative
      colitis were tested for the presence of pANCA by indirect immunofluorescence with
      or without prior absorption with homogenized murine cecal bacteria. pANCA was
      found in 24 of 36 IL10(-/-) mice. In contrast to the human pANCA, both nuclear
      and perinuclear staining was found. Absorption of either human or mouse pANCA
      positive sera with enteric bacterial antigens greatly reduced or abolished the
      specific perinuclear staining of pANCA. We conclude that pANCA occurs not only in
      humans but also in IL19(-/-) mice with colitis and likely represents a cross
      reactivity with enteric bacterial antigens.

PMID- 9533660
TI  - Primary immunodeficiency diseases in Latin America: first report from eight
      countries participating in the LAGID. Latin American Group for Primary
      Immunodeficiency Diseases.
AB  - The Latin American Group for Primary Immunodeficiencies, formed in 1993,
      presently includes 12 countries. One goal was to study the frequency of primary
      immunodeficiencies in various regions of the American continent and to enhance
      knowledge about these diseases among primary-care physicians, as well as
      allergist-immunologists. Important for this purpose was the development of a
      registry of primary immunodeficiencies using a uniform questionnaire and
      computerized database. To date, eight countries have collected information on a
      total of 1428 patients. Predominantly antibody deficiencies were reported in 58%
      of patients, followed by cellular and antibody immunodeficiencies associated with
      other abnormalities in 18%, immunodeficiency syndromes associated with
      granulocyte dysfunction in 8%, phagocytic disorders in 9%, combined cellular and
      antibody immunodeficiencies in 5%, and complement deficiencies in 2% of patients.
      The information gathered from this initial analysis of data will serve to expand
      the patient database to more areas within participating countries and to new
      countries and to increase collaboration toward better diagnosis and treatment of
      these diseases.

PMID- 9533662
TI  - Biobehavioral correlates in migraine: the role of hypersensitivity and
      information-processing dysfunction.
AB  - In this paper we address the role of specific abnormal behavioral patterns (such
      as perfectionism or hypersensitivity) which have been described as psychological
      characteristics in migraine patients. We propose that behavioral abnormalities
      may be the result of a determined cortical hypersensitivity and an associated
      social learning process. New neuro(psycho)physiological data support the concept
      that migraine is a brainstem-related information-processing dysfunction that is
      characterized by cortical hypersensitivity and reduced habituation to stimuli.
      The cortical activity reflects a (time) periodicity and may be due to endogenous
      or exogenous factors. Based on the current understanding of behavioral and
      neurophysiological aspects of migraine, we postulate a two-process model of
      migraine aetiology: (i) a genetically determined hyperactivity of the central
      monoaminergic (catecholaminergic) system, which could be possibly modulated by
      learning processes and (ii) a homeostatic (counter) regulation and mobilization
      of reduced (mitochondrial) energy reserve.

PMID- 9533663
TI  - Neurophysiological approach to primary headache pathophysiology.
AB  - Electroencephalography (EEG), evoked potentials (EP), and electromyography (EMG)
      techniques are useful tools in the clinical assessment of headache and in
      understanding the pathophysiological mechanisms of these pathologies. EEG and EP
      studies in migraine revealed functional abnormalities in cortical electrical
      activity and in sensory processing. EMG studies resulted in pain syndromes
      involving nerves or myofascial structures such as tension-type headache and
      cluster headache. Moreover, it was possible to test the effect of old and new
      drugs with the help of these neurophysiological techniques. An updated review is
      reported of the literature.

PMID- 9533664
TI  - Cerebral hemodynamics in primary headaches: the transcranial Doppler experience.
AB  - This paper is an extensive review of the use of transcranial Doppler (TCD)
      devices in "vascular" forms of headache, and a discussion of the possible
      occurrence of nonunivocal results, particularly in migraine with or without aura.
      Despite the large variability in findings, TCD is a noninvasive, safe, and
      reproducible method for studying hemodynamic phenomena which characterize the
      clinical profile of migraine and cluster headache attacks. Similarly, it can
      detect cerebrovasomotor reactivity to external/internal environmental stimuli, as
      well as responses to pharmacological (therapeutic or diagnostic) agents. Possible
      future applications of TCD in monitoring vasomotor changes in response to
      selective stimuli (sympathetic, neuropeptidergic, etc.) are also considered.

PMID- 9533665
TI  - The effect of national lifestyles.
AB  - Epidemiological surveys show that migraine is global, although not so far
      reported in Eskimos. Where studied, countries show the usual age variations, but
      adult national prevalence figures range between 2 and 35%, indicating that data
      gathering methods need scrutiny. National and religious lifestyles affect eating
      at different times, in varying quantities and types of food; the drinking of
      alcohol and non-alcoholic fluids, as well as climate may also affect migraine.
      More questions than answers are raised to stimulate thinking, observations, and
      further research. Knowledge can derive from seeking and studying differences,
      contradictions, and questioning current beliefs. Can national lifestyles
      influence migraine and what can we learn from such variations?

PMID- 9533666
TI  - Comparative view of the socioeconomic impact of migraine versus low back pain.
AB  - The burden of migraine in terms of cost and impact on socioeconomic indicators is
      still controversial. In a recent comparative study between migraineurs and
      controls from the French general population, we show that only general
      practitioner (GP) consultations and complementary examinations are more frequent
      in migraineurs. In this paper, we compare the socioeconomic impact of migraine
      versus another common neurological disease, low back pain, which has similar
      consequences in term of deficiencies, disabilities, and handicaps. Our study is a
      subproject of the Gazel cohort study, conducted on 20,000 volunteers working in
      the "Electricite et Gaz de France" company. The socioeconomic impact was
      evaluated prospectively by the number of workdays missed between 1989 and 1992 in
      436 subjects with migraine but without low back pain (M group), 590 subjects with
      low back pain but without migraine (L group), 555 subjects with migraine and low
      back pain (ML group), and in 1005 subjects without headache or low back pain (C
      group). Moreover, in 1993 all subjects completed a mailed questionnaire on their
      6-months' history of use of medical services. The number of workdays missed
      during this 4-year period was statistically greater in the ML group (58.1 days),
      followed by the L group (38.4 days), the C group (35.1 days), and the M group
      (31.8 days) (p = 0.0001). For the use of medical services, the results were
      different according to the different indicators: GP consultations were more
      frequent in the ML and M groups, specialist consultations and complementary
      examinations in the L and C groups. In conclusion, migraine and low back pain
      seem to have a similar socioeconomic impact. Absenteeism is particularly high
      when both neurological disorders are present.

PMID- 9533667
TI  - Long-term outcome of migraine.
AB  - Migraine prevalence increases from childhood up until 40 years of age, and
      thereafter declines. Several hypotheses can be advanced to explain the decrease
      in migraine with advancing age: (i) favorable effect of preventive treatments;
      (ii) increased mortality in migraineurs (due to higher vulnerability to other
      fatal diseases); (iii) cohort effect (increased incidence in young subjects);
      (iv) spontaneous remission. The first two theses are poorly supported by data in
      the literature. Although a cohort effect may exist, a spontaneous remission of
      migraine in middle and old age (at least partially due to the loss of sex hormone
      changes after the menopause in females) is the more likely hypothesis. In a small
      subgroup of patients (most of them drug abusers), migraine has a "malignant"
      course and changes into chronic daily headache. The risk factors for a poor
      outcome of migraine have been little studied. In a case-control study, we found
      that a history of head trauma and a long duration of contraceptive intake were
      risk factors for a bad outcome, whilst a long duration of prophylactic treatments
      had a protective effect.

PMID- 9533668
TI  - Medication misuse headache.

PMID- 9533669
TI  - Chronic daily headache: is "cervicogenic headache" one subgroup?
AB  - "Chronic daily headache" should not include cervicogenic headache, which in its
      typical form is a unilateral headache that can be precipitated mechanically; in
      other words, probably an organic disorder. Chronic daily headache as such should
      not be included in the IHS classification.

PMID- 9533670
TI  - Fibromyalgia and headache. Failure of serotonergic analgesia and N-methyl-D
      aspartate-mediated neuronal plasticity: their common clues.
AB  - A defect in serotonergic analgesia and a hyperalgesic state are proposed as
      features common to headache and fibromyalgia. The benefit to both migraine and
      fibromyalgia from inhibiting ionotropic N-methyl-D-aspartate receptor activity
      implies that redundant hyperalgesia-related neuroplastic changes are crucial for
      severe or chronic migraine and primary fibromyalgia. The fact that migraine and
      primary fibromyalgia share some pivotal set-up of serotonergic and excitatory
      amino acid systems led us to analyse epidemiological data supporting the
      hypothesis that analgesic disruption and a consequent hyperalgesic state are
      mechanisms of both migraine and fibromyalgia. Beyond demonstrating the
      comorbidity between migraine and primary fibromyalgia, the data suggest that
      migraine may represent a risk factor for fibromyalgia.

PMID- 9533671
TI  - Psychiatric comorbidity in chronic daily headache.
AB  - Clinical evidence suggests that chronic daily headache (CDH) occurs in
      association with psychopathologies: previous studies have focused particularly on
      migraine. To evaluate this association, we studied, using the DSM-IIIR criteria,
      a population of 88 patients (18M, 70F) affected by CDH (mean duration 7.4 +/- 8.7
      years). We documented the presence of a psychiatric disorder in 90% of this
      population. The most frequent diagnosis was a comorbidity of anxiety and mood
      disorders. The comorbidity of psychiatric disorders and headache has important
      implications as far as treatment is concerned.

PMID- 9533672
TI  - Comprehensive management of headache and depression.
AB  - Migraine is a highly prevalent episodic headache disorder. When migraine and
      depression occur together, therapeutic opportunities, as well as limitations,
      exist. The effective treatment of both migraine and depression begins with making
      an accurate diagnosis and explaining it to the patient. Behavioral interventions,
      such as maintaining a regular schedule, getting adequate sleep and exercise, and
      giving up tobacco, are often useful. In addition, patients with comorbid
      depression often need supportive psychotherapy. Patients with depression often
      need antidepressant therapy independent of their migraine attack frequency.
      Although the mechanism of antidepressants in headache prophylaxis is unknown, it
      is not the result of treating masked depression. Preventive migraine medication
      is usually given daily to decrease the frequency of migraine attacks. For the
      patient with migraine and depression, use an antidepressant. While tricyclic
      antidepressants may be more effective for migraine, selective serotonin reuptake
      inhibitors are just as effective for depression and have fewer side effects. For
      the patient with migraine and epilepsy, or migraine and manic depressive illness,
      divalproex sodium is the drug of choice. Drug combinations are commonly used for
      patients with refractory headache disorders. Some combinations, such as
      antidepressants and beta-blockers, are suggested even in depressed patients.

PMID- 9533673
TI  - Guidelines in medical practice: the legal issues.
AB  - The use of guidelines represents a new culture in medicine-a shift of emphasis
      away from reliance on individual discretion towards greater professionalism and
      accountability. Although they are important vehicles for those who wish to
      evaluate and monitor healthcare practice against recognized standards, this paper
      explores the legal problems surrounding the implementation of guidelines in the
      National Health Service in the UK. The topic is considered from the clinician's
      perspective, but there are also lessons to be learned by managers. There is
      discussion of the difficulty in defining and prioritizing the numerous
      guidelines, and advice is given as to which guidance is the most authoritative.
      The legal consequences of ignoring guidelines are explored, and the paper
      concludes with the view that the time is ripe for clinicians to take the
      initiative in preparing, drafting, and disseminating guidelines before they are
      pre-empted by managers and employers and the future of clinical freedom is called
      into question.

PMID- 9533674
TI  - Treating headache from an evidence base: the Cochrane Collaboration.
AB  - The Cochrane Collaboration uses rigorous and widely accepted methods, together
      with peer-review, to produce systematic reviews of all data of acceptable
      scientific quality relating to specified aspects of healthcare. Review Groups
      exist for a number of areas of medicine and surgery, but at present not headache.
      It is argued that there should be a Cochrane Collaborative Review Group for
      Headache, and that the International Headache Society should foster its creation.
      Some principles are set out. The step from establishing the evidence-base to
      incorporating it in treatment guidelines should be taken circumspectly.

PMID- 9533675
TI  - Headache as a major public health problem: current status.
AB  - Headache is one of the most prevalent neurological disorders diagnosed by
      practising neurologists. It is a public health problem of major concern in all
      countries, and it represents a drain on a country's productivity, its health
      systems, society, individuals, and families. The economic costs involved (direct
      and indirect) and the psychosocial and human costs are enormous burdens on
      society in general. While health status assessments that rely on traditional
      morbidity and mortality rates are of limited use in the evaluation of headache
      patients, it is important to create awareness and acceptance of these disorders
      that cause so much personal suffering and enormous public expense.

PMID- 9533676
TI  - A national neurological excellence centers network.
AB  - The most relevant problems related to the management of neurological disorders
      are (i) the frequent hospitalization in nonspecialist departments, with the need
      for neurological consultation, and (ii) the frequent requests of GPs for highly
      specialized investigations that are very expensive and of little value in
      arriving at a correct diagnosis. In 1996, the Consorzio di Bioingegneria e
      Informatica Medica in Italy realized the CISNet project (in collaboration with
      the Consorzio Istituti Scientifici Neuroscienze e Tecnologie Biomediche and
      funded by the Centro Studi of the National Public Health Council) for the
      implementation of a national neurological excellence centers network (CISNet). In
      the CISNet project, neurologists will be able to give on-line interactive
      consultation and off-line consulting services identifying correct
      diagnostic/therapeutic procedures, evaluating the need for both examination in
      specialist centers and admission to specialized centers, and identifying the most
      appropriate ones.

PMID- 9533677
TI  - Headache coding and diagnostic-related groups: a survey of one year's admissions
      to a neurological department.
AB  - In 1995, the introduction of Diagnostic Related Groups (DRGs) within the Italian
      National Health Service (NHS) significantly changed the mode of payment for
      hospital admissions. The ICD-IX system is the fundamental instrument by which to
      identify various clinical entities; however, its codes still refer to an old
      international classification of diseases. Headache disorders are now diagnosed
      according to the new classification of the International Headache Society, and
      their recognition using ICD-IX codes appears to be increasingly inadequate. We
      evaluated 1-year admissions for "headache" in our Department of Neurology
      according to the new DRG system, and paid particular attention to the problems
      related to compilation of the patient discharge schedule. The most common
      mistakes affecting the definition of DRGs and the admission costs for the NHS
      were also examined.

PMID- 9533678
TI  - Business management of headache centers.
AB  - Economic evaluation of the costs and benefits of a headache center or unit has
      become very important for headache specialists. Many of the problems concerning
      this "financial" approach to headache derive from the model of organization of
      the Headache Unit, which is dependent on the various approaches to healthcare
      practiced in the country considered. So far there are two models of headache
      center that are generally considered: the hospital-based center and the
      independent center. An argument favoring hospital-based headache clinics is the
      lower costs, primarily because of their functional connection with the services
      of a general hospital, i.e., neuroradiology, neurophysiology, routine laboratory
      analysis, etc. Another is that the headache specialist has the possibility to
      visit the patients presenting to the emergency room in the acute phase of
      headache. Independent clinics have greater costs, but are equally as effective as
      hospital-based models.

PMID- 9533679
TI  - How to develop good media relations.
AB  - One of the aims of this paper is to avoid giving readers a headache! People
      suffering from headache are generally not easy to deal with, and headache can
      affect a wide range of people from infants to the elderly. Furthermore, each
      patient experiences the same pathology in a different way. How can we cope with
      these difficulties?

PMID- 9533680
TI  - Television and headache specialists: how to develop an educational model.
AB  - The task for the media is not to educate the audience: the first task for the
      media and especially TV is to inform (and to entertain) the public. The media and
      the journalists are not a public health office. They have to provide the public
      with news. It is not necessary to develop an educational model for TV, or the
      other media, especially for headache. Instead it has to be asked; what can be
      done to inform the public better? What can be done to help the people suffering
      from headache? Therefore it is necessary to develop an educational model for
      practitioners. The question must be: How can they gain the interest of
      journalists? The answer is: Look for news, give journalists news, let them know
      what the current problems are, what is news. Give journalists what they need and
      offer help. That's the best solution.

PMID- 9533681
TI  - Low voltage electroporation of the skin, or is it iontophoresis?

PMID- 9533682
TI  - Simulations of fatty acid-binding proteins suggest sites important for function.
      I. Stearic acid.
AB  - Molecular dynamics simulations of two structurally similar fatty acid-binding
      proteins interacting with stearic acid are described. The calculations relate to
      recent ligand binding measurements and suggest similarities and differences
      between the two systems. Charged and neutral forms of the fatty acid were
      examined. The charged forms led to rapid trajectory divergence, whereas the
      protonated forms remained stable over the length of their 1-ns production
      trajectories. The two protein systems showed similar sets of total interaction
      energies with the ligand. However, the strengths of individual amino acids
      interacting with the ligand differ. Furthermore, covariance analysis of the
      ligand with both protein and water suggests that the stearic acid in the
      adipocyte fatty acid-binding protein is coupled more strongly to the water than
      to the protein. The stearic acid in the muscle fatty acid-binding protein is seen
      to be coupled differentially along the length of the chain to the protein. These
      differences could help to rationalize the stronger binding affinity for stearic
      acid in the human muscle fatty acid-binding protein. An importance scale, based
      on both covariance and interaction energy with the ligand, is proposed to
      identify residues that may be important for binding function.

PMID- 9533683
TI  - Simulations of fatty acid-binding proteins. II. Sites for discrimination of
      monounsaturated ligands.
AB  - Fatty acid binding proteins (FABPs) can discriminate between saturated and
      unsaturated fatty acids via molecular mechanisms that are not understood.
      Molecular dynamics computer calculations are used to suggest the relationship
      between tertiary structure and binding specificity. Three separate 1-ns
      simulations, with explicit solvent, are presented: 1) oleic acid (C18:1 cis)
      bound to adipocyte FABP, 2) oleic acid bound to human muscle FABP, and 3) elaidic
      acid (C18:1 trans) bound to human muscle FABP. The average structural, dynamic,
      and energetic properties of the trajectory were analyzed, as were the motional
      correlations. The molecular dynamics trajectories reveal intriguing differences
      among all three systems. For example, the two proteins have different strengths
      of interaction energy with the ligand and different motional coupling, as seen
      with covariance analysis. This suggests distinctive molecular behavior of
      monounsaturated fatty acids in the two similar proteins. An importance scale,
      based on motional correlation and interaction energy between protein and ligand,
      is proposed, to help identify amino acids involved with the discrimination of
      ligand saturation state or geometric isomerization.

PMID- 9533684
TI  - The coupling of electron transfer and proton translocation: electrostatic
      calculations on Paracoccus denitrificans cytochrome c oxidase.
AB  - We have calculated the electrostatic potential and interaction energies of
      ionizable groups and analyzed the response of the protein environment to redox
      changes in Paracoccus denitrificans cytochrome c oxidase by using a continuum
      dielectric model and finite difference technique. Subsequent Monte Carlo sampling
      of protonation states enabled us to calculate the titration curves of all
      protonatable groups in the enzyme complex. Inclusion of a model membrane allowed
      us to restrict the calculations to the functionally essential subunits I and II.
      Some residues were calculated to have complex titration curves, as a result of
      strong electrostatic coupling, desolvation, and dipolar interactions. Around the
      heme a3-CuB binuclear center, we have identified a cluster of 18 strongly
      interacting residues that account for most of the proton uptake linked to
      electron transfer. This was calculated to be between 0.7 and 1.1 H+ per electron,
      depending on the redox transition considered. A hydroxide ion bound to CuB was
      determined to become protonated to form water upon transfer of the first electron
      to the binuclear site. The bulk of the protonation changes linked to further
      reduction of the heme a3-CuB center was calculated to be due to proton uptake by
      the interacting cluster and Glu(II-78). Upon formation of the three-electron
      reduced state (P1), His325, modeled in an alternative orientation away from CuB,
      was determined to become protonated. The agreement of these results with
      experiment and their relevance in the light of possible mechanisms of redox
      coupled proton transfer are discussed.

PMID- 9533685
TI  - External action of di- and polyamines on maxi calcium-activated potassium
      channels: an electrophysiological and molecular modeling study.
AB  - In this study we compared polyamines to various diamines, and we modeled
      flexibility as well as hydrophobicity properties of these molecules to examine
      possible structural differences that could explain their external effects on the
      channels. The natural polyamines (putrescine, cadaverine, spermidine, spermine)
      and diamines increasing in CH2 chain length from C2 to C12 were used to probe
      maxi calcium-activated potassium (BK) channels in GH3 pituitary tumor cells when
      applied extracellularly. In single-channel recordings we found polyamines as well
      as diamines up to 1,10-diaminodecane to be ineffective in altering channel
      current amplitudes or kinetics. In contrast, 1,12-diamino dodecane (1,12-DD) was
      found to be a reversible blocker, with a blocking site at an electrical distance
      (z delta) of 0.72 within the channel. It reduced single-channel current
      amplitude, mean channel open time, and channel open probability. In computer
      simulations structural data, such as flexibility, hydration, and log D values,
      were calculated. 1,12-DD showed the largest flexibility of all diamines (minimum
      N-N distance 9.9 A) combined with a marked hydrophobicity due to a 4-5 A
      hydrophobic intersegment between hydrophilic ends in the molecule, as confirmed
      by GRID water probe maps and a log D value of -1.82 at pH 7.2. We propose that
      the amount of hydration of the molecule, more than its flexibility, constitutes
      an essential parameter for its ability to act as a channel blocker.

PMID- 9533686
TI  - Binding of basic peptides to membranes produces lateral domains enriched in the
      acidic lipids phosphatidylserine and phosphatidylinositol 4,5-bisphosphate: an
      electrostatic model and experimental results.
AB  - Direct fluorescence digital imaging microscopy observations demonstrate that a
      basic peptide corresponding to the effector region of the myristoylated alanine
      rich C kinase substrate (MARCKS) self-assembles into membrane domains enriched in
      the acidic phospholipids phosphatidylserine (PS) and phosphatidylinositol 4,5
      bisphosphate (PIP2). We show here that pentalysine, which corresponds to the
      first five residues of the MARCKS effector region peptide and binds to membranes
      through electrostatic interactions, also forms domains enriched in PS and PIP2.
      We present a simple model of domain formation that represents the decrease in the
      free energy of the system as the sum of two contributions: the free energy of
      mixing of neutral and acidic lipids and the electrostatic free energy. The first
      contribution is always positive and opposes domain formation, whereas the second
      contribution may become negative and, at low ionic strength, overcome the first
      contribution. Our model, based on Gouy-Chapman-Stern theory, makes four
      predictions: 1) multivalent basic ligands, for which the membrane binding is a
      steep function of the mole fraction of acidic lipid, form domains enriched in
      acidic lipids; domains break up at high concentrations of either 2) basic ligand
      or 3) monovalent salt; and 4) if multivalent anionic lipids (e.g., PIP2) are
      present in trace concentrations in the membrane, they partition strongly into the
      domains. These predictions agree qualitatively with experimental data obtained
      with pentalysine and spermine, another basic ligand.

PMID- 9533687
TI  - Steady-state compartmentalization of lipid membranes by active proteins.
AB  - Using a simple microscopic model of lipid-protein interactions, based on the
      hydrophobic matching principle, we study some generic aspects of lipid-membrane
      compartmentalization controlled by a dispersion of active integral membrane
      proteins. The activity of the proteins is simulated by conformational excitations
      governed by an external drive, and the deexcitation is controlled by interaction
      of the protein with its lipid surroundings. In response to the flux of energy
      into the proteins from the environment and the subsequent dissipation of energy
      into the lipid bilayer, the lipid-protein assembly reorganizes into a steady
      state structure with a typical length scale determined by the strength of the
      external drive. In the specific case of a mixed dimyristoylphosphatidylcholine
      distearoylphosphatidylcholine bilayer in the gel-fluid coexistence region, it is
      shown explicitly by computer simulation that the activity of an integral membrane
      protein can lead to a compartmentalization of the lipid-bilayer membrane. The
      compartmentalization is related to the dynamical process of phase separation and
      lipid domain formation.

PMID- 9533688
TI  - Conservation of the conformation of the porphyrin macrocycle in hemoproteins.
AB  - The out-of-plane distortions of porphyrins in hemoproteins are characterized by
      displacements along the lowest-frequency out-of-plane normal coordinates of the
      D4h-symmetric macrocycle. X-ray crystal structures are analyzed using a
      computational procedure developed for determining these orthogonal displacements.
      The x-ray crystal structures of the heme groups are described within experimental
      error, using the set composed of only the lowest frequency normal coordinate of
      each out-of-plane symmetry type. That is, the distortion is accurately simulated
      by a linear combination of these orthonormal deformations, which include saddling
      (B2u), ruffling (B1u), doming (A2u), waving (Eg), and propellering (A1u). For
      example, orthonormal structural decomposition of the hemes in deoxymyoglobins
      reveals a predominantly dom heme deformation combined with a smaller wav(y)
      deformation. Generally, the heme conformation is remarkably similar for proteins
      from different species. For cytochromes c, the conformation is conserved as long
      as the amino acids between the cysteine linkages to the heme are homologous.
      Differences occur if this short segment varies in the number or type of residues,
      suggesting that this small segment causes the nonplanar distortion. Some
      noncovalently linked hemes like those in the peroxidases also have highly
      conserved characteristic distortions. Conservation occurs even for some proteins
      with a large natural variation in the amino acid sequence.

PMID- 9533689
TI  - Determination of the gelsolin binding site on F-actin: implications for severing
      and capping.
AB  - Gelsolin is a six-domain protein that regulates actin assembly by severing,
      capping, and nucleating filaments. We have used electron cryomicroscopy and
      helical reconstruction to identify its binding site on F-actin. To obtain fully
      decorated filaments under severing conditions, we have studied a derivative (G2
      6) that has a reduced severing efficiency compared to gelsolin. A three
      dimensional reconstruction of G2-6:F-actin was obtained by electron
      cryomicroscopy and helical reconstruction. The structure shows that gelsolin
      bridges two longitudinally associated monomers when it binds the filament. The F
      actin binding region of G2-6 is centered axially at subdomain 3 and radially
      between subdomains 1 and 3 of the upper actin monomer. Our results suggest that
      for severing to occur, both gelsolin and actin undergo large conformational
      changes.

PMID- 9533690
TI  - Looping dynamics of linear DNA molecules and the effect of DNA curvature: a study
      by Brownian dynamics simulation.
AB  - A Brownian dynamics (BD) model described in the accompanying paper (Klenin, K.,
      H. Merlitz, and J. Langowski. 1998. A Brownian dynamics program for the
      simulation of linear and circular DNA, and other wormlike chain polyelectrolytes.
      Biophys. J. 74:000-000) has been used for computing the end-to-end distance
      distribution function, the cyclization probability, and the cyclization kinetics
      of linear DNA fragments between 120 and 470 basepairs with optional insertion of
      DNA bends. Protein-mediated DNA loop formation was modeled by varying the
      reaction distance for cyclization between 0 and 10 nm. The low cyclization
      probability of DNA fragments shorter than the Kuhn length (300 bp) is enhanced by
      several orders of magnitude when the cyclization is mediated by a protein bridge
      of 10 nm diameter, and/or when the DNA is bent. From the BD trajectories, end-to
      end collision frequencies were computed. Typical rates for loop formation of
      linear DNAs are 1.3 x 10(3) s(-1) (235 bp) and 4.8 x 10(2) s(-1) (470 bp), while
      the insertion of a 120 degree bend in the center increases this rate to 3.0 x
      10(4) s(-1) (235 bp) and 5.5 x 10(3) s(-1) (470 bp), respectively. The duration
      of each encounter is between 0.05 and 0.5 micros for these DNAs. The results are
      discussed in the context of the interaction of transcription activator proteins.

PMID- 9533691
TI  - A Brownian dynamics program for the simulation of linear and circular DNA and
      other wormlike chain polyelectrolytes.
AB  - For the interpretation of solution structural and dynamic data of linear and
      circular DNA molecules in the kb range, and for the prediction of the effect of
      local structural changes on the global conformation of such DNAs, we have
      developed an efficient and easy way to set up a program based on a second-order
      explicit Brownian dynamics algorithm. The DNA is modeled by a chain of rigid
      segments interacting through harmonic spring potentials for bending, torsion, and
      stretching. The electrostatics are handled using precalculated energy tables for
      the interactions between DNA segments as a function of relative orientation and
      distance. Hydrodynamic interactions are treated using the Rotne-Prager tensor.
      While maintaining acceptable precision, the simulation can be accelerated by
      recalculating this tensor only once in a certain number of steps.

PMID- 9533692
TI  - Computer simulations of carbon monoxide photodissociation in myoglobin:
      structural interpretation of the B states.
AB  - The early diffusion processes of a photodissociated ligand (carbon monoxide) in
      sperm whale myoglobin and its Phe29 mutant are studied computationally. An
      explicit solvent model is employed in which the protein is embedded in a box of
      at least 2300 water molecules. Electrostatic interactions are accounted for by
      using the particle mesh Ewald. Two hundred seventy molecular dynamics
      trajectories are computed for 10 ps. Different models of solvation and the
      ligand, and their influence on the diffusion are examined. The two B states of
      the CO are identified as "docking" sites in the heme pocket. The sites have a
      similar angle with respect to the heme normal, but differ in the orientation in
      the plane. The computational detection of the B states is stable under a
      reasonable variation of simulation conditions. However, in some trajectories only
      one of the states is observed. It is therefore necessary to use extensive
      simulation data to probe these states. Comparison to diffraction experiments and
      spectroscopy is performed. The shape of the experimental infrared spectra is
      computed. The overall linewidth is in an agreement with experiment. The
      contributions to the linewidth (van der Waals and electrostatic interactions) are
      discussed.

PMID- 9533693
TI  - A model for the recovery kinetics of rod phototransduction, based on the
      enzymatic deactivation of rhodopsin.
AB  - We propose a model for the recovery of the retinal rod photoresponse after a
      short stimulus. The approach describes the enzymatic deactivation of the
      photoactivated receptor, rhodopsin, by simple enzyme kinetics. An important
      feature of this description is that the R* deactivation obeys different time
      laws, depending on the numbers of R* formed per disc membrane and available
      enzyme molecules. If the enzyme works below substrate saturation, the rate of
      deactivation depends linearly on the number of R*, whereas for substrate
      saturation a hyperbolic relation--the well-known Michaelis-Menten equation-
      applies. This dichotomy is used to explain experimental finding that the relation
      between the saturation time of the photoresponse after short illumination and the
      flash strength has two sharply separated branches for low and high flash
      intensities (up to approximately 10% bleaching). By relating both branches to
      properties of the enzymatic rhodopsin deactivation, the new model transcends the
      classical notion of a constant characteristic lifetime of activated rhodopsin.
      With parameters that are plausible in the light of the available data and the
      additional information that the deactivating enzyme, rhodopsin kinase, and the
      signaling G-protein, transducin, compete for the active receptor, the slopes of
      the saturation function are correctly reproduced.

PMID- 9533694
TI  - Reduction of an eight-state mechanism of cotransport to a six-state model using a
      new computer program.
AB  - A computer program was developed to allow easy derivation of steady-state
      velocity and binding equations for multireactant mechanisms including or without
      rapid equilibrium segments. Its usefulness is illustrated by deriving the rate
      equation of the most general sequential iso ordered ter ter mechanism of
      cotransport in which two Na+ ions bind first to the carrier and mirror symmetry
      is assumed. It is demonstrated that this mechanism cannot be easily reduced to a
      previously proposed six-state model of Na+-D-glucose cotransport, which also
      includes a number of implicit assumptions. In fact, the latter model may only be
      valid over a restricted range of Na+ concentrations or when assuming very strong
      positive cooperativity for Na+ binding to the glucose symporter within a rapid
      equilibrium segment. We thus propose an equivalent eight-state model in which the
      concept of positive cooperativity is best explained within the framework of a
      polymeric structure of the transport protein involving a minimum number of two
      transport-competent and identical subunits. This model also includes an
      obligatory slow isomerization step between the Na+ and glucose-binding sequences,
      the nature of which might reflect the presence of functionally asymmetrical
      subunits.

PMID- 9533695
TI  - Modalities of distortion of physiological voltage signals by patch-clamp
      amplifiers: a modeling study.
AB  - An extensive evaluation of the possible alterations affecting physiological
      voltage signals recorded with patch-clamp amplifiers (PCAs) working in the
      current-clamp (CC) mode was carried out by following a modeling approach. The PCA
      output voltage and current signals obtained during CC recordings performed under
      simplified experimental conditions were exploited to determine the equations
      describing the generation of error currents and voltage distortions by PCAs. The
      functions thus obtained were used to construct models of PCAs working in the CC
      mode, which were coupled to numerical simulations of neuronal bioelectrical
      behavior; this allowed us to evaluate the effects of the same PCAs on different
      physiological membrane-voltage events. The models revealed that rapid signals
      such as fast action potentials are preferentially affected, whereas slower
      events, such as low-threshold spikes, are less altered. Prominent effects of
      model PCAs on fast action potentials were alterations of their amplitude,
      duration, depolarization and repolarization speeds, and, most notably, the
      generation of spurious afterhyperpolarizations. Processes like regular firing and
      burst firing could also be altered, under particular conditions, by the model
      PCAs. When a cell consisting of more than one single intracellular compartment
      was considered, the model PCAs distorted fast equalization transients.
      Furthermore, the effects of different experimental and cellular parameters
      (series resistance, cell capacitance, temperature) on PCA-generated artifacts
      were analyzed. Finally, the simulations indicated that no off-line correction
      based on manipulations of the error-current signals returned by the PCAs can be
      successfully performed in the attempt to recover unperturbed voltage signals,
      because of alterations of the overall current flowing through the cell-PCA
      system.

PMID- 9533696
TI  - Electrical properties of skin at moderate voltages: contribution of appendageal
      macropores.
AB  - The electrical properties of human skin in the range of the applied voltages
      between 0.2 and 60 V are modeled theoretically and measured experimentally. Two
      parallel electric current pathways are considered: one crossing lipid-corneocyte
      matrix and the other going through skin appendages. The appendageal ducts are
      modeled as long tubes with distributed electrical parameters. For both transport
      systems, equations taking into account the electroporation of lipid lamella in
      the case the lipid-corneocyte matrix or the walls of the appendageal ducts in the
      case of the skin appendages are derived. Numerical solutions of these nonlinear
      equations are compared with published data and the results of our own
      experiments. The current-time response of the skin during the application of
      rectangular pulses of different voltage amplitudes show a profound similarity
      with the same characteristics in model and plasma membrane electroporation. A
      comparison of the theory and the experiment shows that a significant (up to three
      orders of magnitude) drop of skin resistance due to electrotreatment can be
      explained by electroporation of different substructures of stratum corneum. At
      relatively low voltages (U < 30 V) this drop of skin resistance can be attributed
      to electroporation of the appendageal ducts. At higher voltages (U > 30 V),
      electroporation of the lipid-corneocyte matrix leads to an additional drop of
      skin resistance. These theoretical findings are in a good agreement with the
      experimental results and literature data.

PMID- 9533697
TI  - Measurement of the lateral diffusion of dipalmitoylphosphatidylcholine adsorbed
      on silica beads in the absence and presence of melittin: a 31P two-dimensional
      exchange solid-state NMR study.
AB  - 31P two-dimensional exchange solid-state NMR spectroscopy was used to measure the
      lateral diffusion, D(L), in the fluid phase of dipalmitoylphosphatidylcholine
      (DPPC) in the presence and absence of melittin. The use of a spherical solid
      support with a radius of 320 +/- 20 nm, on which lipids and peptides are adsorbed
      together, and a novel way of analyzing the two-dimensional exchange patterns
      afforded a narrow distribution of D(L) centered at a value of (8.8 +/- 0.5) x 10(
      8) cm2/s for the pure lipid system and a large distribution of D(L) spanning 1 x
      10(-8) to 10 x 10(-8) cm2/s for the lipids in the presence of melittin. In
      addition, the determination of D(L) for nonsupported DPPC multilamellar vesicles
      (MLVs) suggests that the support does not slow down the lipid diffusion and that
      the radii of the bilayers vary from 300 to 800 nm. Finally, the DPPC-melittin
      complex is stabilized at the surface of the silica beads in the gel phase,
      opening the way to further study of the interaction between melittin and DPPC.

PMID- 9533698
TI  - Surface properties of native human plasma lipoproteins and lipoprotein models.
AB  - Plasma lipoprotein surface properties are important but poorly understood
      determinants of lipoprotein catabolism. To elucidate the relation between surface
      properties and surface reactivity, the physical properties of surface monolayers
      of native lipoproteins and lipoprotein models were investigated by fluorescent
      probes of surface lipid fluidity, surface lateral diffusion, and interfacial
      polarity, and by their reactivity to Naja melanoleuca phospholipase A2 (PLA2).
      Native lipoproteins were human very low, low-, and subclass 3 high-density
      lipoproteins (VLDL, LDL, and HDL3); models were 1-palmitoyl-2-oleoyl-sn-glycero-3
      phosphocholine (POPC) or its ether analog in single-bilayer vesicles, large and
      small microemulsions of POPC and triolein, and reassembled HDL (apolipoprotein A
      I plus phospholipid). Among lipoproteins, surface lipid fluidity increased in the
      order HDL3 < LDL < VLDL, varying inversely with their (protein +
      cholesterol)/phospholipid ratios. Models resembled VLDL in fluidity. Both lateral
      mobility in the surface monolayer and polarity of the interfacial region were
      lower in native lipoproteins than in models. Among native lipoproteins and
      models, increased fluidity in the surface monolayer was associated with increased
      reactivity to PLA2. Addition of cholesterol (up to 20 mol%) to models had little
      effect on PLA2 activity, whereas the addition of apolipoprotein C-III stimulated
      it. Single-bilayer vesicles, phospholipid-triolein microemulsions, and VLDL have
      surface monolayers that are quantitatively similar, and distinct from those of
      LDL and HDL3. Surface property and enzymatic reactivity differences between
      lipoproteins and models were associated with differences in surface monolayer
      protein and cholesterol contents. Thus differences in the surface properties that
      regulate lipolytic reactivity are a predictable function of surface composition.

PMID- 9533699
TI  - Molecular order and dynamics in bilayers consisting of highly polyunsaturated
      phospholipids.
AB  - The time-resolved fluorescence emission and decay of fluorescence anisotropy of
      1,6-diphenyl-1,3,5-hexatriene (DPH) was used to characterize equilibrium and
      dynamic bilayer structural properties of symmetrically substituted
      phosphatidylcholines (PCs) with acyl chains containing no, one, four, or six
      double bonds and mixed-chain phosphatidylcholines with a saturated sn-1 chain and
      one, four, or six double bonds in the sn-2 chain. Both the Brownian rotational
      diffusion (BRD) model and the wobble-in-cone model were fit to all differential
      polarization data, and the descriptions of the data provided by the BRD model
      were found to be statistically superior. Global analysis of differential
      polarization data revealed two statistically equivalent solutions. The solution
      corresponding to a bimodal orientational distribution function, f(theta), was
      selected based on the effects of temperature on f(theta) and previous
      measurements on fixed, oriented bilayers. The overall equilibrium acyl chain
      order in these bilayers was analyzed by comparing the orientational probability
      distribution for DPH, f(theta) sin theta, with a random orientational
      distribution. Orientational order decreased and probe dynamics increased in mixed
      chain species as the unsaturation of the sn-2 chain was increased. The degree of
      orientational order dropped dramatically in the dipolyunsaturated species
      compared with the mixed-chain phosphatidylcholines, which contained a
      polyunsaturated sn-2 chain. In terms of both orientational order and probe
      dynamics, the differences between the highly polyunsaturated species and the
      monounsaturated species were much greater than the differences between the
      monounsaturated species and a disaturated PC.

PMID- 9533700
TI  - Change of motion and localization of cholesterol molecule during L(alpha)-H(II)
      transition.
AB  - Formation of the inverted hexagonal (H(II)) phase from the lamellar (L(alpha))
      phase of bovine brain-extracted phosphatidylcholine (BBPC) and
      phosphatidylethanolamine (BBPE) was investigated using 31P-NMR with or without
      cholesterol. When the ratio of BBPC to BBPE was 1:1, the H(II) formation was
      observed in the presence of 33 mol% cholesterol (i.e., BBPC:BBPE:cholesterol =
      1:1:1) at 47 degrees C. The fraction of the H(II) phase in the
      BBPC/BBPE/cholesterol system could be controlled by the addition of
      dioleoylglycerol. The change of molecular motion of cholesterol affected by the
      H(II) formation was measured at various ratios of the L(alpha) to H(II) phase
      with the time-resolved fluorescence depolarization method, using
      dehydroergosterol as a fluorescent probe. It is observed that the motion of
      cholesterol became vigorous in the mixture state of the L(alpha) and the H(II)
      phases compared to that in the L(alpha) or the H(II) phase only. These facts show
      that cholesterol has the strong ability to induce the H(II) phase, probably by
      special molecular motion, which includes change of its location from the
      headgroup area to the acyl-chain area.

PMID- 9533701
TI  - Polymorphism of POPE/cholesterol system: a 2H nuclear magnetic resonance and
      infrared spectroscopic investigation.
AB  - It is well established that cholesterol induces the formation of a liquid-ordered
      phase in phosphatidylcholine (PC) bilayers. The goal of this work is to examine
      the influence of cholesterol on phosphatidylethanolamine polymorphism. The
      behavior of 1-palmitoyl-2-oleoyl-phosphatidylethanolamine (POPE)/cholesterol
      mixtures was characterized using infrared and 2H nuclear magnetic resonance (NMR)
      spectroscopy (using POPE bearing a perdeuterated palmitoyl chain in the latter
      case). Our results reveal that cholesterol induces the formation of a liquid
      ordered phase in POPE membranes, similar to those observed for various
      PC/cholesterol systems. However, the coexistence region of the gel and the liquid
      ordered phases is different from that proposed for PC/cholesterol systems. The
      results indicate a progressive broadening of the gel-to-fluid phase transition,
      suggesting the absence of an eutectic. In addition, there is a progressive
      downshift of the end of the transition for cholesterol content higher than 10 mol
      %. Cholesterol has an ordering effect on the acyl chains of POPE, but it is less
      pronounced than for the PC equivalent. This study also shows that the cholesterol
      effect on the lamellar-to-hexagonal (L(alpha)-H(II)) phase transition is not
      monotonous. It shifts the transition toward the low temperatures between 0 and 30
      mol % cholesterol but shifts it toward the high temperatures when cholesterol
      content is higher than 30 mol %. The change in conformational order of the lipid
      acyl chains, as probed by the shift of the symmetric methylene C-H stretching,
      shows concerted variations. Finally, we show that cholesterol maintains its chain
      ordering effect in the hexagonal phase.

PMID- 9533702
TI  - Polarity profiles in oriented and dispersed phosphatidylcholine bilayers are
      different: an electron spin resonance study.
AB  - A novel method was utilized to accurately measure the z- component of the nuclear
      hyperfine interaction tensor, Azz, of a chain-labeled lipid, 16PC, and a
      headgroup-labeled lipid, dipalmitoylphosphatidyl-tempocholine (DPPTC), in
      macroscopically oriented dipalmitoylphosphatidylcholine (DPPC) and
      dimyristoylphosphatidylcholine (DMPC) membranes, which were compared with the Azz
      values of the two labels in dispersions of the same lipids in the gel phase. We
      found that the Azz values of 16PC (DPPTC) in the oriented DPPC and DMPC bilayers
      are approximately 1 Gauss smaller (greater) than in the corresponding
      dispersions. These results indicate that the headgroup region is more polar in
      macroscopically oriented bilayers than in dispersions, whereas in the chain
      region, the order in polarity is reversed. This is consistent with previous
      results on partial molar volumes in the liquid-crystal phase. Differences in the
      morphology of the macroscopically oriented and dispersed bilayers, which might be
      responsible, are discussed. Nonlinear least-squares fits of the electron spin
      resonance spectra of DPPTC in DPPC show that there is a substantial orienting
      potential in the headgroup region of dispersions that is lipid phase dependent.
      However, in oriented membrane samples hydrated in 100% relative humidity, this
      orienting potential is very weak.

PMID- 9533704
TI  - Adhesion forces of lipids in a phospholipid membrane studied by molecular
      dynamics simulations.
AB  - Lipid adhesion forces can be measured using several experimental techniques, but
      none of these techniques provide insight on the atomic level. Therefore, we
      performed extensive nonequilibrium molecular dynamics simulations of a
      phospholipid membrane in the liquid-crystalline phase out of which individual
      lipid molecules were pulled. In our method, as an idealization of the
      experimental setups, we have simply attached a harmonic spring to one of the
      lipid headgroup atoms. Upon retraction of the spring, the force needed to drag
      the lipid out of the membrane is recorded. By simulating different retraction
      rates, we were able to investigate the high pull rate part of the dynamical
      spectrum of lipid adhesion forces. We find that the adhesion force increases
      along the unbinding path, until the point of rupture is reached. The maximum
      value of the adhesion force, the rupture force, decreases as the pull rate
      becomes slower, and eventually enters a friction-dominated regime. The computed
      bond lengths depend on the rate of rupture, and show some scatter due to the
      nonequilibrium nature of the experiment. On average, the bond length increases
      from approximately 1.7 nm to 2.3 nm as the rates go down. Conformational analyses
      elucidate the detailed mechanism of lipid-membrane bond rupture. We present
      results of over 15 ns of membrane simulations. Implications for the
      interpretation and understanding of experimental rupture data are discussed.

PMID- 9533703
TI  - A new "gel-like" phase in dodecyl maltoside-lipid mixtures: implications in
      solubilization and reconstitution studies.
AB  - The interaction of dodecyl maltoside with lipids was investigated through the
      studies of solubilization and reconstitution processes. The solubilization of
      large unilamellar liposomes was analyzed through changes in turbidity and cryo
      transmission electron microscopy. Solubilization was well described by the three
      stage model previously reported for other detergents, and the critical
      detergent/phospholipid ratios at which lamellar-to-micellar transition occurred
      (Rsat = 1 mol/mol) and finished (Rsol = 1.6 mol/mol) were determined. The vesicle
      micelle transition was further observed in the vitrified hydrated state by cryo
      transmission electron microscopy. A striking feature of the solubilization
      process by dodecyl maltoside was the discovery of a new phase consisting of a
      very viscous "gel-like" sample. It is shown that this equilibrium cohesive phase
      is composed of long filamentous thread-like micelles, over microns in length.
      Similar structures were observed upon solubilization of sonicated liposomes,
      multilamellar liposomes, or biological Ca2+ ATPase membranes. This "gel-like"
      phase was also visualized during the process of liposome reconstitution after
      detergent removal from lipid-dodecyl maltoside micelles. The rate of detergent
      removal, controlled through the use of SM2 Bio-Beads, was demonstrated to
      drastically influence the morphology of reconstituted liposomes with a propensity
      for multilamellar liposome formation upon slow transition through the "gel-like"
      phase. Finally, on the basis of these observations, the mechanisms of dodecyl
      maltoside-mediated reconstitution of bacteriorhodopsin were analyzed, and optimal
      conditions for reconstitution were defined.

PMID- 9533705
TI  - Comparative study of the effects of several n-alkanes on phospholipid hexagonal
      phases.
AB  - The effects of a series of normal alkanes (decane, dodecane, tetradecane,
      hexadecane, and octadecane) on the hexagonal H(II) structures containing
      dioleoylphosphatidylethanolamine (DOPE) and dioleoylphosphatidylcholine (DOPC)
      were studied using x-ray diffraction and osmotic stress. The alkanes affect
      structural dimensions and the monolayer intrinsic curvature and bending modulus.
      The alkane effects are chain-length dependent and are attributed to their
      different distribution within the H(II) structure. The data suggest that short
      chain alkanes are more uniformly distributed within the H(II) hydrocarbon regions
      and change the curvature and bending modulus of the monolayer, whereas longer
      chain alkanes appear confined more to the interstitial region and do not change
      the curvature and bending modulus.

PMID- 9533706
TI  - Transglutaminase-induced cross-linking between subdomain 2 of G-actin and the 636
      642 lysine-rich loop of myosin subfragment 1.
AB  - G-actin was covalently cross-linked with S1 in a bacterial transglutaminase
      catalyzed reaction. The cross-linking sites were identified with the help of
      fluorescent probes and limited proteolysis as the Gln-41 on the DNase I binding
      loop of subdomain 2 in G-actin and a lysine-rich loop (residues 636-642) on the
      S1 heavy chain. The same lysine-rich loop was cross-linked to another region of G
      actin in a former study (Combeau, C., D. Didry, and M-F. Carlier. 1992. J. Biol.
      Chem. 267:14038-14046). This indicates the existence of more than one G-actin-S1
      complex. In contrast to G-actin, no cross-linking was induced between F-actin and
      S1 by the transglutaminase reaction. This shows that in F-actin the inner part of
      the DNase I binding loop, where Gln-41 is located, is not accessible for S1. The
      cross-linked G-actin-S1 polymerized upon addition of 2 mM MgCl2 as indicated by
      electron microscopy and sedimentation experiments. The filaments obtained from
      the polymerization of cross-linked actin and S1 were much shorter than the
      control actin filaments. The ATPase activity of the cross-linked S1 was not
      activated by actin, whereas the K+ (EDTA)-activated ATPase activity of S1 was
      unaffected by the cross-linking. The cross-linking between G-actin and S1 was not
      influenced by the exchange of the tightly bound calcium to magnesium; however, it
      was inhibited by the exchange of the actin-bound ATP to ADP. This finding
      supports the view that the structure of the DNase binding loop in ADP-G-actin is
      somewhere between the structures of ATP-G-actin and F-actin.

PMID- 9533707
TI  - A gel electrophoresis study of the competitive effects of monovalent counterion
      on the extent of divalent counterions binding to DNA.
AB  - The behavior of alkaline earth metal cations (Mg2+ and Ca2+) and transition metal
      cations (Zn2+ and Cu2+) interacting with lambda-DNA-HindIII fragments ranging
      from 2,027 to 23,130 bp in Tris-borate-EDTA buffer solutions was investigated.
      The divalent counterions competed with Tris+ and Na+ for binding to polyion DNA,
      and the competition binding situations were investigated by measuring the
      reduction of the DNA mobility, by pulsed- or constant-field gel electrophoresis.
      The interaction of Mg2+ with DNA was intensively studied over a wide range of
      Mg2+ concentrations. In addition, we examined the competition binding as a
      function of ionic strength and DNA size. To compare valence effects, we studied
      Co(NH3)6(3+) interaction with DNA fragments under conditions similar to that of
      Mg2+. At relatively low Mg2+ concentration, the normalized titration curves of
      DNA mobility were well fit by Manning's two-variable counterion condensation (CC)
      theory. The agreement between the predicted value (total charge neutralization
      fraction theta) from Manning's CC theory and the data based on our measured DNA
      electrophoretic mobility reduction was consistent under our experimental
      conditions. In contrast to alkaline earth metal cations (Mg2+ and Ca2+),
      different binding behaviors were observed for the transition metal cations (Zn2+
      and Cu2+). These differences highlight the usefulness of our reduced DNA
      electrophoretic mobility measurement approach to describing cation interactions
      with polyelectrolyte DNA.

PMID- 9533709
TI  - Structure and dynamics of the antibiotic peptide PGLa in membranes by solution
      and solid-state nuclear magnetic resonance spectroscopy.
AB  - PGLa, a 21-residue member of the magainin family of antibiotic peptides, is shown
      to be helical between residues 6 and 21 when associated with detergent micelles
      by multidimensional solution nuclear magnetic resonance (NMR) spectroscopy. Solid
      state NMR experiments on specifically 15N-labeled peptides in oriented
      phospholipid bilayer samples show that the helix axis is parallel to the plane of
      the bilayers. 15N solid-state NMR powder pattern line shapes obtained on
      unoriented samples demonstrate that the amino-terminal residues are highly mobile
      and that the fluctuations of backbone sites decrease from Ala6 toward the carboxy
      terminus. The powder pattern observed for 15N-labeled Ala20 is essentially that
      expected for a rigid site. These findings are similar to those for the 23-residue
      magainin2 peptide in membrane environments.

PMID- 9533708
TI  - Spectroscopic analysis of halothane binding to the plasma membrane Ca2+-ATPase.
AB  - The intrinsic tryptophan (Trp) fluorescence of the plasma membrane Ca2+-ATPase
      (PMCA) is significantly quenched by halothane, a volatile anesthetic common in
      clinical practice. It has been proposed that halothane inhibition of the Ca2+
      ATPase activity results from conformational changes following anesthetic binding
      in the enzyme. We have investigated whether the observed quenching reflects
      halothane binding to PMCA. We have shown that the quenching is dose dependent and
      saturable and can be fitted to a binding curve with an equilibrium constant
      K(Hal) = 2.1 mM, a concentration at which the anesthetic approximately half
      maximally inhibits the Ca2+-ATPase activity. The relatively low sensitivity of
      halothane quenching of Trp fluorescence to the concentration of
      phosphatidylcholine and detergent in the PMCA preparation concurs with the
      quenching resulting from anesthetic binding in the PMCA molecule. Analysis of the
      Trp fluorescence quenching by acrylamide indicates that the Trp residues are not
      considerably exposed to the solvent (Stern-Volmer quenching constant of 2.9 M(
      1)) and do not differ significantly in their accessibility to halothane. Other
      volatile anesthetics, diethyl ether and diisopropyl ether, reduce the quenching
      caused by halothane in a dose-dependent manner, suggesting halothane displacement
      from its binding site(s). These observations indicate that halothane quenching of
      intrinsic Trp fluorescence of PMCA results from anesthetic binding to the
      protein. The analysis, used as a complementary approach, provides new information
      to the still rudimentary understanding of the process of anesthetic interaction
      with membrane proteins.

PMID- 9533710
TI  - Transmembrane helix stability: the effect of helix-helix interactions studied by
      Fourier transform infrared spectroscopy.
AB  - We have measured, using infrared spectroscopy, the hydrogen/deuterium exchange
      rates of the amide protons in the photosynthetic antenna of Rhodospirillum
      rubrum. These measurements were made not only on the intact protein in detergent
      solution but also on two dissociated forms (B820 and B777). We have, on the basis
      of our knowledge of the structure of this protein, been able to assign the
      various groups of amide protons that exchange with different time constants to
      distinct regions of the protein. The most protected group of protons that we
      observe exchanging with time constants near 6000 min we assign to the
      transmembrane helices. The slow exchange rates measured for the amide protons of
      the transmembrane helices of this protein in detergent solution may indicate a
      destabilization of the helices in detergent solution compared with the membrane.
      This group of protons is progressively destabilized by stepwise dissociation of
      the antenna protein, and this destabilization is greater than we can account for
      by increases in solvent accessibility. We suggest that the observed loss of amide
      proton protection in the transmembrane helices as they are dissociated might be
      due to an increase in the helix flexibility and breathing motions as interactions
      between helices are reduced.

PMID- 9533711
TI  - A synchrotron x-ray diffraction study of developing chick corneas.
AB  - To study some ultrastructural aspects of developing chick corneas we performed a
      synchrotron x-ray diffraction analysis of 22 specimens obtained daily from
      developmental day 10 through day 19. Before day 12 of development in chicks we
      were unable to detect a meridional x-ray diffraction pattern from cornea. Neither
      were we able to record a first-order equatorial x-ray reflection at this time.
      Normally, these reflections are present in corneal x-ray patterns, arising from,
      respectively, the periodic axial electron density of fibrillar collagen and the
      lattice-like arrangement of the fibrils. By day 12 of development we could detect
      the third- and fifth-order meridional reflections (indicating increased amounts
      of collagen) and a first-order equatorial reflection (implying that more collagen
      was regularly arranged). The third- and fifth-order meridional reflections became
      more intense as the tissue matured, suggestive of a continued deposition of
      fibrillar collagen, and the scattering angle of the interfibrillar maximum
      increased, suggesting that regularly arranged collagen was becoming more closely
      packed with maturation. In embryonic chick corneas, the establishment of an
      orderly, fairly compacted matrix of collagen fibrils may be one of the main
      events underlying the acquisition of corneal transparency.

PMID- 9533713
TI  - Determination of orientational order parameters from 2H NMR spectra of
      magnetically partially oriented lipid bilayers.
AB  - The partial orientation of multilamellar vesicles (MLVs) in high magnetic fields
      is known to affect the shape of 2H NMR spectra. There are numerical methods for
      extracting either the orientational order parameters of lipid molecules for a
      random distribution of domain orientations in the sample, or the distribution of
      orientations for a known set of spectral anisotropies. A first attempt at
      determining the orientational order parameters in the presence of an unknown
      nonrandom distribution of orientations is presented. The numerical method is
      based on the Tikhonov regularization algorithm. It is tested using simulated
      partially oriented spectra. An experimental spectrum of a phospholipid-ether
      mixture in water is analyzed as an example. The experimental spectrum is
      consistent with an ellipsoidal shape of MLVs with a ratio of semiaxes of
      approximately 3.4.

PMID- 9533712
TI  - Molecular orientation distributions in protein films: III. Yeast cytochrome c
      immobilized on pyridyl disulfide-capped phospholipid bilayers.
AB  - Molecular orientation in a hydrated monolayer film of yeast cytochrome c,
      immobilized via disulfide bonding between Cys-102 and a pyridyl disulfide-capped
      phospholipid bilayer deposited from an air-water interface onto glass substrates,
      was investigated. The orientation distribution of the heme groups in the protein
      film was determined using a combination of absorption linear dichroism, measured
      in a planarintegrated optical waveguide-attenuated total reflection geometry- and
      fluorescence anisotropy, measured in a total internal reflection geometry. A
      gaussian model for the orientation distribution was used to recover the mean heme
      tilt angle and angular distribution about the mean, which were 40 and 11 degrees,
      respectively. Additional experiments showed that a large fraction of the
      cytochrome c was disulfide bonded to the bilayer, which correlates with the high
      degree of macroscopic order in the protein film. However, a subpopulation of
      yeast cytochrome c molecules in the film (approximately 30% of the total)
      appeared to be nonspecifically adsorbed. The orientation distribution of this
      subpopulation was found to be much broader than the specifically bound fraction.

PMID- 9533714
TI  - Analysis of various sequence-specific triplexes by electron and atomic force
      microscopies.
AB  - Sequence-specific interactions of 20-mer G,A-containing triple helix-forming
      oligonucleotides (TFOs) and bis-PNAs (peptide nucleic acids) with double-stranded
      DNA was visualized by electron (EM) and atomic force (AFM) microscopies.
      Triplexes formed by biotinylated TFOs are easily detected by both EM and AFM in
      which streptavidin is a marker. AFM images of the unlabeled triplex within a long
      plasmid DNA show a approximately 0.4-nm height increment of the double helix
      within the target site position. TFOs conjugated to a 74-nt-long oligonucleotide
      forming a 33-bp-long hairpin form extremely stable triplexes with the target site
      that are readily imaged by both EM and AFM as protruding DNA. The short duplex
      protrudes in a perpendicular direction relative to the double helix axis, either
      in the plane of the support or out of it. In the latter case, the apparent height
      of the protrusion is approximately 1.5 nm, when that of the triplex site is
      increased by 0.3-0.4 nm. Triplex formation by bis-PNA, in which two decamers of
      PNA are connected via a flexible linker, causes deformations of the double helix
      at the target site, which is readily detected as kinks by both EM and AFM.
      Moreover, AFM shows that these kinks are often accompanied by an increase in the
      DNA apparent height of approximately 35%. This work shows the first direct
      visualization of sequence-specific interaction of TFOs and PNAs, with their
      target sequences within long plasmid DNAs, through the measurements of the
      apparent height of the DNA double helix by AFM.

PMID- 9533715
TI  - Trapping of DNA in nonuniform oscillating electric fields.
AB  - DNA molecules can be manipulated in aqueous solution in a manner analogous to
      optical trapping. Due to the induction of an electric dipole, DNA molecules are
      pulled by a gradient force to regions of high electric field strength. Molecules
      can be locally trapped in an oscillating field using strips of very thin gold
      film to generate strong electric fields with steep gradients. Spatial control
      over the trapped molecules is achieved because they are confined to a width of
      approximately 5 microm along the edges of the gold-film strips. By mixing static
      and oscillating electric fields, trapped molecules can be moved from one edge to
      another or made to follow precise trajectories along the edges. This phenomenon
      should be useful in microdevices for manipulation of small quantities or single
      molecules of DNA.

PMID- 9533716
TI  - Electron tomography of ice-embedded prokaryotic cells.
AB  - Whole cells of archaea were embedded in vitreous ice by plunge freezing and
      investigated by automated energy-filtered electron tomography at 120 kV. The
      embedded cells were between 300 and 750 nm thick, and their structures were
      reconstructed to a resolution of 20-40 nm from tilt series comprising 50-140
      images. The dose was kept within tolerable limits. A resolution of 20 nm allowed
      visualization of the individual stalks of the S-layer of Pyrobaculum aerophilum
      cells, which had undergone partial lysis, in three dimensions. The attainable
      resolution for low-dose electron tomography under different experimental
      conditions was theoretically investigated in terms of the specimen thickness. To
      obtain 2-nm resolution at 120 kV (300 kV), the specimen must not be thicker than
      100 nm (150 nm). For a resolution of 10 nm, the maximum thickness is 450 nm (700
      nm). An accelerating voltage of 300 kV is advantageous, mainly for specimens
      thicker than 100 nm. Experimental investigations so far have resulted in a
      resolution that is worse by a factor of 2-5 as compared to theory.

PMID- 9533717
TI  - Trapping and wiggling: elastohydrodynamics of driven microfilaments.
AB  - We present an analysis of the planar motion of single semiflexible filaments
      subject to viscous drag or point forcing. These are the relevant forces in
      dynamic experiments designed to measure biopolymer bending moduli. By analogy
      with the "Stokes problems" in hydrodynamics (motion of a viscous fluid induced by
      that of a wall bounding the fluid), we consider the motion of a polymer, one end
      of which is moved in an impulsive or oscillatory way. Analytical solutions for
      the time-dependent shapes of such moving polymers are obtained within an analysis
      applicable to small-amplitude deformations. In the case of oscillatory driving,
      particular attention is paid to a characteristic length determined by the
      frequency of oscillation, the polymer persistence length, and the viscous drag
      coefficient. Experiments on actin filaments manipulated with optical traps
      confirm the scaling law predicted by the analysis and provide a new technique for
      measuring the elastic bending modulus. Exploiting this model, we also present a
      reanalysis of several published experiments on microtubules.

PMID- 9533718
TI  - Regulation of exocytotic fusion by cell inflation.
AB  - We have inflated patch-clamped mast cells by 3.8 +/- 1.6 times their volume by
      applying a hydrostatic pressure of 5-15 cm H2O to the interior of the patch
      pipette. Inflation did not cause changes in the cell membrane conductance and
      caused only a small reversible change in the cell membrane capacitance (36 +/- 5
      fF/cm H2O). The specific cell membrane capacitance of inflated cells was found to
      be 0.5 microF/cm2. High-resolution capacitance recordings showed that inflation
      reduced the frequency of exocytotic fusion events by approximately 70-fold, with
      the remaining fusion events showing an unusual time course. Shortly after the
      pressure was returned to 0 cm H2O, mast cells regained their normal size and
      appearance and degranulated completely, even after remaining inflated for up to
      60 min. We interpret these observations as an indication that inflated mast cells
      reversibly disassemble the structures that regulate exocytotic fusion. Upon
      returning to its normal size, the cell cytosol reassembles the fusion pore
      scaffolds and allows exocytosis to proceed, suggesting that exocytotic fusion
      does not require soluble proteins. Reassembly of the fusion pore can be prevented
      by inflating the cells with solutions containing the protease pronase, which
      completely blocked exocytosis. We also interpret these results as evidence that
      the activity of the fusion pore is sensitive to the tension of the plasma
      membrane.

PMID- 9533719
TI  - Two-dimensional tracking of ncd motility by back focal plane interferometry.
AB  - A technique for detecting the displacement of micron-sized optically trapped
      probes using far-field interference is introduced, theoretically explained, and
      used to study the motility of the ncd motor protein. Bead motions in the focal
      plane relative to the optical trap were detected by measuring laser intensity
      shifts in the back-focal plane of the microscope condenser by projection on a
      quadrant diode. This detection method is two-dimensional, largely independent of
      the position of the trap in the field of view and has approximately 10-micros
      time resolution. The high resolution makes it possible to apply spectral analysis
      to measure dynamic parameters such as local viscosity and attachment compliance.
      A simple quantitative theory for back-focal-plane detection was derived that
      shows that the laser intensity shifts are caused primarily by a far-field
      interference effect. The theory predicts the detector response to bead
      displacement, without adjustable parameters, with good accuracy. To demonstrate
      the potential of the method, the ATP-dependent motility of ncd, a kinesin-related
      motor protein, was observed with an in vitro bead assay. A fusion protein
      consisting of truncated ncd (amino acids 195-685) fused with glutathione-S
      transferase was adsorbed to silica beads, and the axial and lateral motions of
      the beads along the microtubule surface were observed with high spatial and
      temporal resolution. The average axial velocity of the ncd-coated beads was 230
      +/- 30 nm/s (average +/- SD). Spectral analysis of bead motion showed the
      increase in viscous drag near the surface; we also found that any elastic
      constraints of the moving motors are much smaller than the constraints due to
      binding in the presence of the nonhydrolyzable nucleotide
      adenylylimidodiphosphate.

PMID- 9533720
TI  - DNA sequence sampling of the Streptococcus pneumoniae genome to identify novel
      targets for antibiotic development.
AB  - We initiated a survey of the Streptococcus pneumoniae genome by DNA sequence
      sampling. More than 9,500 random DNA sequences of approximately 500 bases average
      length were determined. Partial sequences sufficient to identify approximately
      95% of the aminoacyl tRNA synthetase genes and ribosomal protein (rps) genes were
      found by comparing the database of partial sequences to known sequences from
      other organisms. Many genes involved in DNA replication, repair, and mutagenesis
      are present in S. pneumoniae. Genes for the major subunits of RNA polymerase are
      also present, as are genes for two alternative sigma factors, rpoD and rpoN. Many
      genes necessary for amino acid or cofactor biosynthesis and aerobic energy
      metabolism in other bacteria appear to be absent from the S. pneumoniae genome. A
      number of genes involved in cell wall biosynthesis and septation were identified,
      including six homologs to different penicillin binding proteins. Interestingly,
      four genes involved in the addition of D-alanine to lipoteicoic acid in other
      gram positive bacteria were found, even though the lipoteicoic acid in S.
      pneumoniae has not been shown to contain D-alanine. The S. pneumoniae genome
      contains a number of chaperonin genes similar to those found in other bacteria,
      but apparently does not contain genes involved in the type III secretion commonly
      observed in gram negative pathogens. The G+C content of S. pneumoniae genomic DNA
      is approximately 43 mole percent and the size of the genome is approximately 2.0
      Mb as determined by pulsed-field gel electrophoresis. Many of the genes
      identified by sequence sampling have been physically mapped to the 19 different
      SmaI fragments derived from the S. pneumoniae genome. The database of random
      genome sequence tags (GSTs) provides the starting material for determining the
      complete genome sequence, gene disruption analysis, and comparative genomics to
      identify novel targets for antibiotic development.

PMID- 9533721
TI  - Capsule genetics in Streptococcus pneumoniae and a possible role for
      transposition in the generation of the type 3 locus.
AB  - The capsule genes of Streptococcus pneumoniae have a cassette-like organization
      in which the type-specific biosynthetic genes are flanked by genes shared among
      the different capsular serotypes. This general organization has been identified
      in the capsule loci of all serotypes analyzed to date, but significant
      differences that may help explain novel capsule type formation are beginning to
      emerge. In particular, analysis of the type 3 locus has revealed its most
      striking feature to be a preponderance of partial genes that have homology to
      sequences involved in polysaccharide biosynthesis and transposition. The
      predicted proteins of cps3M, the most downstream type 3-specific gene, and tnpA
      and plpA, the non-type-specific flanking sequences downstream of cps3M, have
      homologies with phosphomutases, transposases, and peptide permeases,
      respectively. All three of these sequences are truncated when compared to their
      respective homologs. Mutation and transcription analyses of these partial
      sequences showed that none of these sequences is essential for type 3
      polysaccharide synthesis but that all are transcribed. Partial sequences were
      also identified in the region upstream of the type 3-specific genes. The type 3
      locus structure is conserved among independent type 3 isolates but similar
      deletions are not apparent in the common, non-type-specific flanking sequences in
      other capsular types. A role for transposition-mediated events in the generation
      of the type 3 locus, and possibly other pneumococcal capsule loci, is suggested
      by these findings.

PMID- 9533722
TI  - Versatility of choline-binding domain.

PMID- 9533723
TI  - Lipopolysaccharide and peptidoglycan: CD14-dependent bacterial inducers of
      inflammation.
AB  - Surface structures of bacteria contribute to the microbial pathogenic potential
      and are capable of causing local and generalized inflammatory reactions. Among
      these factors, endotoxin and peptidoglycan are of particular medical importance.
      Both toxic bacterial polymers are now recognized to interact with the same
      cellular receptor, the CD14 molecule, which is expressed on different types of
      immune cells, in particular, monocytes/macrophages. The interaction between these
      bacterial activators and CD14 leads to the production of endogenous mediators
      such as tumor necrosis factor alpha, interleukin 1 (IL-1), and IL-6, which are
      ultimately responsible for phlogistic responses. The fact that CD14 recognizes
      not only endotoxin and peptidoglycan but also other glycosyl-based microbial
      polymers suggests that this cellular surface molecule represents a lectin.

PMID- 9533724
TI  - Streptococcus mitis with unusually high level resistance to beta-lactam
      antibiotics.
AB  - Penicillin-resistant oral streptococci constitute the genetic reservoir for beta
      lactam resistance in S. pneumoniae. Here we report the isolation of clinical
      strains of S. mitis with unusually high MIC values for beta-lactam antibiotics;
      resistance to benzylpenicillin was 64 microg/ml and to cefotaxime 128 microg/ml.
      Among the beta-lactam compounds tested, only the carbapenems imipenem and
      meropenem showed MICs below 32 microg/ml. Both S. mitis strains were resistant to
      tetracycline and were highly resistant to aminoglycosides. Pulse field mapping of
      chromosomal DNA revealed identical patterns in both strains, indicating clonal
      identity of the two isolates. Using chromosomal S. mitis DNA, the laboratory
      strain S. pneumoniae R6 could be transformed in four successive steps to
      cefotaxime and benzylpenicillin resistance of 64 microg/ml. The results exemplify
      the importance of commensal streptococci for the development of cefotaxime
      resistance in S. pneumoniae.

PMID- 9533725
TI  - Serotype 19A variants of the Spanish serotype 23F multiresistant clone of
      Streptococcus pneumoniae.
AB  - Multiply-antibiotic-resistant isolates of serogroup 19 Streptococcus pneumoniae,
      possessing altered penicillin-binding protein (PBP) 1A, 2B, and 2X genes that are
      indistinguishable from those of the Spanish multiresistant serogroup 23F clone,
      are now commonly encountered in Spain. Those isolates that have been serotyped
      express type 19F capsular polysaccharide. Serotyping of further isolates, and
      hybridization using a serotype 19F-specific probe, has shown that some of them
      are serotype 19A, rather than 19F. The Spanish multiresistant serotype 19A, 19F,
      and 23F multiresistant strains were all shown to be very closely related in
      overall genotype, as they were indistinguishable by REP-PCR and by the sequencing
      of internal fragments of three house-keeping genes. The serotype 19A
      multiresistant strains, like the serotype 19F multiresistant strains, therefore
      appear to be a serotype variant of the Spanish multiresistant serotype 23F clone,
      which presumably has arisen by recombination at the capsular locus.

PMID- 9533726
TI  - Increasing incidence of antibiotic resistance in shigellas from humans in England
      and Wales: recommendations for therapy.
AB  - Since 1983 the incidence of resistance to ampicillin in Shigella dysenteriae, Sh.
      flexneri, and Sh. boydii infections in England and Wales has increased from 42%
      to 65% and the incidence of resistance to trimethoprim, from 6% to 64%.
      Furthermore, of 1524 strains received in 1995-1996, 46% were resistant to both of
      these antimicrobials. For Sh. sonnei almost 50% of isolates were resistant to
      ampicillin or trimethoprim and 15% were resistant to both of these
      antimicrobials. These results demonstrate that if antibiotic therapy had been
      indicated for infections with Sh. dysenteriae, Sh. flexneri, and Sh. boydii, then
      treatment with either ampicillin or trimethoprim may have been ineffective in
      almost 50% of cases and for Sh. sonnei, in 15% of cases. It is concluded that if
      it is necessary to commence treatment before the results of laboratory-based
      sensitivity tests are available, the best options would be to use nalidixic acid
      for children and a fluoroquinolone antibiotic such as ciprofloxacin or ofloxacin,
      for adults.

PMID- 9533727
TI  - Emergence of penicillin resistance in recurrent pneumococcal endocarditis in an
      HIV-infected patient.
AB  - The emergence of antibiotic resistance in Streptococcus pneumoniae poses a
      particular threat to HIV-infected patients. These patients are at increased risk
      of invasive pneumococcal disease and may respond poorly to pneumococcal
      vaccination. We describe an HIV-infected patient with recurrent aortic valve
      endocarditis due to the same serotype of S. pneumoniae (19A) despite appropriate
      treatment with penicillin and immunoprophylaxis. The pneumococcus responsible for
      the second episode of endocarditis was susceptible to cefotaxime (MIC of 0.06
      microg/ml), but was no longer susceptible to penicillin (MIC of 0.25 microg/ml).
      The patient was treated successfully with 4 weeks of intravenous ceftriaxone.

PMID- 9533728
TI  - Molecular evolution of rifampicin resistance in Streptococcus pneumoniae.
AB  - Rifampicin resistance has arisen in several different species of bacteria because
      of alterations to one or more regions in the target of the antibiotic, the beta
      subunit of RNA polymerase encoded by rpoB. Nucleotide sequence analysis of a 270
      bp fragment of rpoB from 16 clinical rifampicin-susceptible isolates of
      Streptococcus pneumoniae, 8 clinical rifampicin-resistant isolates, and 3
      spontaneous rifampicin-resistant mutants, has revealed that, as with previously
      examined species, point mutations within the cluster I region of rpoB, at sites
      encoding Asp516 and HiS526, also confer resistance to rifampicin in this
      important human pathogen. Moreover, the residues within cluster I, that were
      altered within the rifampicin-resistant mutants of S. pneumoniae, were in the
      same position as those previously found to alter in resistant isolates of
      Escherichia coli and Mycobacterium tuberculosis. Sequence analysis of rpoB, both
      from these isolates of S. pneumoniae and from two strains of S. mitis, reveals
      that, among a number of clinical isolates, resistance to rifampicin in S.
      pneumoniae has arisen by point mutation. However, the nucleotide sequence of rpoB
      from one isolate examined suggests that interspecies gene transfer may also have
      played a role in the evolution of rifampicin-resistance in S. pneumoniae.

PMID- 9533729
TI  - Introduction and clonal spread of penicillin- and trimethoprim/sulfamethoxazole
      resistant Streptococcus pneumoniae, serotype 9V, in southern Sweden.
AB  - As part of an intervention project, all patients in Malmohus county with a
      culture positive for penicillin-resistant pneumococci, MIC > or =0.5 mg/L (PRP),
      have been registered since January 1995. Nasopharyngeal specimens were obtained
      from family members and close contacts of identified carriers. Children were
      denied attendance at regular day-care until PRP-negative. In 1995 and 1996, PRP
      were isolated from 882 individuals, 364 of whom had clinical infection and the
      remaining of whom were asymptomatic carriers. In 49%, the PRP were of serogroup
      9, with MIC of penicillin 0.5-2.0 mg/L and resistance to
      trimethoprim/sulfamethoxazole. Further analyses with serotyping and genetic
      fingerprinting suggested strongly that most of the isolates belonged to a single
      serotype 9V clone. Month by month, an apparently continuous spread appeared from
      one municipality to a neighboring one. In most communities, the serotype 9V PRP
      appeared and disappeared within a few months. The active procedures of the
      intervention project may have limited the spread of the clone in the county.

PMID- 9533730
TI  - The molecular mechanisms of tetracycline resistance in the pneumococcus.
AB  - Tetracycline resistance in the pneumococcus is a result of the acquisition of one
      of two resistance determinants, tet(M) or tet(O). These genes encode ribosomal
      protection proteins that have homology to the elongation factors G and Tu. Tet(M)
      and Tet(O) both have GTPase activity that appears to be important in the
      displacement of tetracycline from the ribosome. Modification of tRNA may also be
      important for tetracycline resistance. Transcription of tet(M) is thought to be
      regulated by transcriptional attenuation. Transcription of tet(O) is
      constitutive, however, upstream of the gene are sequences that also appear to be
      involved in transcriptional attenuation. tet(M) is transferred on the conjugative
      transposons, Tn1545 and Tn5151. It is not yet known whether tet(O) is transported
      on transposons or plasmids, or whether it is chromosomally integrated, in
      pneumococci.

PMID- 9533731
TI  - The use of artificial neural networks methodology in the assessment of
      "vulnerability" to heroin use among army corps soldiers: a preliminary study of
      170 cases inside the Military Hospital of Legal Medicine of Verona.
AB  - This article describes a preliminary study of screening/diagnostic instruments
      for prediction for large-scale application in the military field at the
      Neuropsychiatric Department of the Military Hospital of Legal Medicine of Verona
      and for the prevention of self-destructive behaviors, particularly through the
      use of drugs. 170 subjects divided into three subsamples were examined. The first
      subsample was characterized by a strong tendency towards normalcy, the second by
      a strong tendency towards pathology, and the third by a great variety of
      expressions of psychological and social problems, which were not necessarily
      related to drug use. These subjects were administered a questionnaire designed
      according to Squashing Theory principles (Buscema, 1994a). Answers were processed
      by an Artificial Neural Network created by Semeion in Rome (Buscema, 1996) and
      were compared with a standard clinical psychiatric assessment report and with the
      results of psychodiagnostic tests. Results document ANNs' remarkable ability to
      recognize subjects with declared, in exordium and "at risk" pathological
      behaviors. Blind results on learning and trial samples show a very high
      predictive capacity (over 90%). A comparison with the examined subjects' clinical
      report and the results of the first follow-up also document very high agreements.
      The broad variation of answers obtained in the third subsample allows further
      methodological reflections on the contribution of Artificial Neural Networks and
      Squashing Theory to the study of deviance, for both sociologists and clinicians,
      and not only for those in the field of drug addiction.

PMID- 9533732
TI  - Artificial neural networks for drug vulnerability recognition and dynamic
      scenarios simulation.
AB  - Semeion researchers have developed and used different kinds of Artificial Neural
      Networks (ANN) in order to process selected, "standard" data coming from drug
      users and from people who never used drugs before. In the first step a collection
      of 112 general variables, not traditionally connected to drug user's behavior,
      were collected from a sample of 545 people (223 heroin addicted and 322 non
      users). Different types of ANNs were used to test the capability of the system to
      classify the drug users and the non-drug users correctly. A special ANN tool,
      created by Semeion, was also used to prune the number of the independent
      variables. The ANN selected for this first experiment was a Supervised Feed
      Forward Network, whose equations were enhanced by Semeion researchers. For the
      validation of the capability of generalization of the ANN, the Training-Testing
      protocol was used. This ANN was able, in the Testing phase, to classify
      approximately 95% of the sample with accuracy. A special sensitivity tool
      selected only 47 among the 112 independent variables as necessary to train the
      ANN. In the second step, different types of ANN were tested on the new 47
      variables to decide which kind of ANN was better able to classify the sample.
      This benchmark included the following ANNs: a) Back Propagation with Soft Max; b)
      Learning Vector Quantization; c) Logicon Projection; d) Radial Basis Function; e)
      Squash (Semeion Network); f) Fuzzy Art Map; g) Modular Neural Network. In the
      third step a Constraint Satisfaction Network, specifically created by Semeion,
      was used to simulate a dynamic fuzzy map of the drug user's world; that is, which
      fuzzy, or approximate, variables are critical to decide the fuzzy membership of a
      subject from the fuzzy membership of the drug users to the fuzzy membership of
      non-users and vice versa.

PMID- 9533733
TI  - Use of a constraint satisfaction network model for the evaluation of the
      methadone treatments of drug addicts.
AB  - Constraint Satisfaction Networks were used by Semeion, a Research Center of
      Science of Communication, in order to analyze drug-addict patient data files,
      provided by the Jerusalem Methadone Treatment Center. The short and partial
      analysis carried out in this article is presented to show how this high
      technology can be a support for treatment staff in order to improve the quality
      and the timeliness of the necessary intervention with patients. One of the
      problems for which the networks could offer support is, for example, the
      individuation or "matching" of the most suitable therapy for the patient during
      the treatment planning phase. In this field the networks need to analyze data
      files of patients in therapy at different centers, with the results collected
      after many years of observation. What follows, obviously, only has demonstrative
      values.

PMID- 9533734
TI  - MAIA project: software for the management of toxicodependence treatment process.
AB  - This chapter reviews the importance of information management in a therapeutic
      community, how to select the data collected by the interview and features of the
      software and its fitting in an operative context. New sections are projected to
      help staff who diagnose treatment candidates and treat patients. Use of
      statistical analysis as an instrument for management of therapeutic communities
      is based on the experience of "Centro Solidarieta di Modena". Some examples are
      included on the population of "Centro Solidarieta di Modena". Artificial neural
      networks have a viable role for treatment (primary, secondary and tertiary).

PMID- 9533735
TI  - Planning for alcohol-problem prevention through complex systems modeling: results
      from SimCom.
AB  - This article describes a computer-based model of alcohol use and misuse
      intervention called SimCom. This generic model, based on the best available
      scientific knowledge, incorporates eight interaction subsystems. When loaded with
      actual data from a locality, the model has the ability to "act like" this
      location and can be used to forecast the future effects of alternative prevention
      strategies. The article describes benchmark testing of a model for the state of
      California, including projected prevention strategies for that state.

PMID- 9533736
TI  - Artificial neural networks for the identification of the differences between
      "light" and "heavy" alcoholics, starting from five nonlinear biological
      variables.
AB  - This article makes a comparison among three types of evaluation systems based on
      a set of data composed of "heavy" alcoholics and "light" alcoholics. The three
      systems are: 1) a system based on genetic algorithms called BEAGLE; b) seven
      different types of Artificial Neural Networks; c) a metasystem called MetaNet.
      The technical aim was to compare the classification capability of these three
      systems in terms of two classes ("heavy" alcoholics and "light" alcoholics). From
      the results obtained, the MetaNet system stand out. Globally, it has the best
      result, followed by the two Artificial Neural Networks, Squash and Logicon
      Projection. The results obtained prove that the advanced elaboration data systems
      applied in the social and health fields can be employed in prevention programs
      having an aim to reduce the social impact of certain pathologies correlated with
      different kinds of dependence.

PMID- 9533737
TI  - International migration destination forecast concerning the region "Lazio.".
AB  - Artificial Neural Networks (ANN) have been applied to different kinds of
      problems, when it was necessary to simulate and forecast how nonlinear dynamic
      complex systems worked since the mid 1980's. Currently, ANNs are proposed either
      as a substitute technique for database analysis or alternating with more
      traditional classical statistical analysis. This article presents the results of
      a statistical and a Neural Network analysis, applied to a sociological database
      in order to systematically explore how these models work, their applications, and
      both their strong and weak points.

PMID- 9533738
TI  - Palomar project: predicting school renouncing dropouts, using the artificial
      neural networks as a support for educational policy decisions.
AB  - The "Palomar" project confronts two problem situations that are partly
      independent and partly connected to the Italian schooling system: unstable
      participation in school such as drop out and educational guidance. Our concern is
      that of a set of phenomena which consists of ceasing compulsory education,
      repetition of a year at school, school "drop outs", irregular compulsory
      attendance and delays in the course of studies. The "Palomar" project is designed
      to offer educators and administrators who want to effectively intervene with
      these complex problems to furnish school guidance services as an instrument able
      to: 1. Predict: creating a system able to predict in advance (not in a "cause
      effect" way but as an approximation): a) which students are at "risk" for school
      destabilization or failure; b) what are the prototypical characteristics of these
      students; c) which students among those studied are more likely to "destabilize"
      or fail in school; in which course of study does each student have the greatest
      chance of success; d) which, among the variables studied and appropriately
      weighted for each student, will predict the successful grade, analyzed for each
      possible course of studies. 2. Optimize: selecting and focusing on a student on
      the basis of the information given. It is possible: a) to point out which
      personal factors (relational, familial, student, disciplinary, economical) need
      to be reinforced in order to improve the school performances of each selected
      student, both to prevent or limit "dropping out" desertion or failure and to
      raise the performances in the chosen school course as much as possible; b) on the
      basis of what was mentioned above, to simulate the possible support measures to
      increase the efficacy of the considered intervention; c) to choose for each
      student the appropriate intervention strategy capable of obtaining the maximum
      result and the maximum efficacy in the given conditions. 3. Verify: when the
      strategy of intervention has been decided and we proceed with its implementation,
      it is possible to periodically verify ("follow-up"), through subsequent
      administration of the form, the outcome variations elapsed in the prediction of
      school success or failure. This makes it possible to verify in itinere the
      efficacy of the interventions carried out and, if necessary, to create variations
      and adjustments. 4. Produce scenarios: the application field of the Prediction
      System with Artificial Neural Networks can also be one of a group of students, of
      one or more organized units (for example a class, a school, or a group of
      schools). In this case the Prediction System ANN using the program SCHEMA
      (Buscema, 1996b) is able to: a) determine intervention strategies in order to
      optimize and to produce the maximum results of a group of students as the one of
      a class; b) optimize the formative route of a whole institute in order to prevent
      or limit the need for school guidance.

PMID- 9533739
TI  - The role of social determinants on men's and women's mobility in Italy. A
      comparison of discriminant analysis and artificial neural networks.
AB  - The paper focuses on the role of the spouse's occupation as a resource for mobile
      individuals, from the perspective that social positions are held by families,
      rather than by individuals. Three groups are confronted in terms of the role of
      the key variables and other relevant factors: men whose spouse does not have a
      paid job (group 1), men and women whose spouse has a paid job (group 2 and 3).
      The data set is provided by the national survey on social mobility in Italy,
      carried out in 1985; social achievements of members of the three groups are
      considered, including social origins and destinations, social position
      corresponding to respondent's first job, cultural background (educational
      achievement of respondent's father and mother found), respondent's education and
      spouse's social position. The techniques used are discriminant analysis and back
      propagation Neural Networks. Both techniques traced a clear boundary between
      group 1 and groups 2 and 3, which were discriminated mainly on the basis of the
      spouse's occupation; Artificial Neural Networks reached better classification
      results and allowed a deeper insight into the nonlinear effects of the
      discriminating variables for the three groups.

PMID- 9533740
TI  - Application of artificial neural networks to eating disorders.
AB  - An experimental application of Artificial Neural Networks to Eating Disorders is
      presented. The sample, composed of 172 cases (all women) collected at the Centre
      for the Diagnosis and Treatment of Eating Disorders of the 1st Medical Division
      of the St. Eugenio Hospital of Rome, was subdivided, on the basis of the
      diagnosis made by the specialist of the St. Eugenio, into four classes: Anorexia
      Nervosa (AN), Nervous Bulimia (NB), Binge Eating Disorders (BED) and Psychogenic
      Eating Disorders that are Not Otherwise Specified (PED-NOS). The data base was
      composed of 124 different variables: generic information, alimentary behavior,
      eventual treatment and hospitalization, substance use, menstrual cycles, weight
      and height, hematochemical and instrumental examinations, psychodiagnostic tests,
      etc. The goal of this experiment was to verify the accuracy of the Neural
      Networks in recognising anorexic and bulimic patients. This article describes 6
      experiments, using a Feed Forward Neural Network, each one using different
      variables. Starting from only the generic variables (life styles, family
      environment, etc.) and hematoclinical and instrumental examinations, a Neural
      Networks provided 86.94% of the prediction precision. This work is meant to be a
      first contribution to creating diagnostic procedures for Eating Disorders, that
      would be simple and easy-to-use by professionals who are neither psychologists
      nor psychiatrists nor psychotherapists but who are, however, among the first to
      meet these patients and who are therefore called upon to give such patients the
      very first pieces of advice on seeking proper treatment.

PMID- 9533741
TI  - A neural network investigation of the crucial facets of urban sustainability.
AB  - This paper focuses on the concept of a sustainable city and its theoretical
      implications for the Italian urban system. Urban sustainability is based on
      positive interactions among three different urban subsystems: social, economic
      and physical, where social well-being coexists with economic development and
      environmental quality. This utopian scenario does not appear in the existing
      cities. The aesthetic quality of natural and man-made environment is often
      associated with marginality and poverty, labor market variety and urban
      efficiency coexisting with pollution, criminality and high settlement costs.
      Moreover, since each city differs institutionally, historically, culturally and
      economically, few attempts have been implemented to build a comparative synthetic
      vision of the urban sustainability in different cities. The interactions among
      these selected systems are complex and unpredictable and present the opportunity
      for a new methodology of scientific investigation: the connectionistic approach.
      The dual aim of this study is to: investigate the underlying relationships among
      the three subsystems with a set of social, economic and physical attributes of
      the chief towns of a Province in Italy and ; verify if this underlying structure
      could reproduce the heterogeneity of urban realities, allowing one to distinguish
      groups of cities with different assets or drawbacks in their sustainability. The
      Data Base (DB), composed of 43 attributes for 95 cities, was processed by Self
      Reflexive Neural Networks (SRNN) (Buscema, 1995). These Networks are a useful
      instrument of investigation and analogic questioning of the Data Base. Once the
      SRNN has learned the structure of the weights from the DB, by querying the
      network with the maximization or minimization of specific groups of attributes,
      it is possible to read the related properties and to rank the cities' urban
      profile.

PMID- 9533742
TI  - Unionisation in a comparative neural network model: a trade union membership
      prediction in 12 states.
AB  - The sociometric and theoretical models traditionally associated with the
      determinants of unionisation and based on international comparisons, generally
      use linear analysis of a restricted number of complex variables. The
      effectiveness of such models often have an unsatisfactory result. In this study a
      different theoretical and methodological approach has been used. It is based on a
      integrated scheme made by transposing the principles of the "Squashing Theory"
      (Buscema, 1994) into the social field, by the connectionist paradigm, and by the
      Artificial Neural Networks (ANN). This has permitted the carrying out of a larger
      data base (49 variables, 12 Nations, 12 Years maximum time interval), the
      adjusting of a model that has an elevated explanatory capacity (in terms of open
      variance) an ulterior capacity of generalization (in terms of a one-year span)
      and of metageneralization (in terms of generalization to nonprocessed nations).
      What emerges is surely the need for more and greater in-depth study of
      socializing facts which follow such aspects.

PMID- 9533743
TI  - Handling the pediatric tumor.

PMID- 9533744
TI  - Specimen collection and preparation in fine-needle aspirations in children.
AB  - Fine-needle aspiration is of proven benefit in the pediatric population. For the
      procedure to be of maximum benefit, several aspects unique to children and
      pediatric lesions must be taken into account. Based on the experience of
      approximately 2,500 fine-needle aspirations performed in children over a 17-year
      period, we discuss techniques pertaining to specimen collection and preparation,
      including adequate control of the patient and selective triage of aspirates.

PMID- 9533745
TI  - Guidelines for the diagnosis of leukemia or lymphoma in children.
AB  - Our progress in understanding and treating pediatric acute leukemia and lymphoma
      is one of the success stories of cancer biology and management. Event-free
      survival for children with acute leukemia or lymphoma has improved progressively
      during the past four decades. The advances in the cell and molecular biology of
      acute leukemia and lymphoma that have been made can help determine both prognosis
      and therapy; however, the pathologic evaluation of bone marrow and lymph node
      specimens must be directed appropriately to benefit from these advances. We
      present guidelines for the pathologic evaluation of bone marrow and lymph node
      specimens to maximize the chance that each patient will benefit from our
      increased understanding of these diseases.

PMID- 9533746
TI  - Neuroblastoma and peripheral neuroectodermal tumors.
AB  - Peripheral neuroblastic tumors in childhood present unique problems in terms of
      diagnosis, classification, and histologic determinants of prognosis. The proper
      specimen handling of these neoplasms requires integration of gross and
      microscopic pathologic examination along with cytogenetic, immunohistochemical,
      and electron microscopy studies. The appropriate gross examination and processing
      of these tumors are described with particular emphasis on ancillary studies.
      Important special studies such as immunohistochemistry, flow cytometry, and
      genetic and molecular oncologic investigation are stressed, and the appropriate
      methods of processing materials for these studies are discussed. The handling of
      small biopsy specimens, fine-needle aspirates, or both is also addressed. The
      staging of neuroblastoma varies according to Pediatric Oncology Group and
      Children's Cancer Study Group systems, and the importance of obtaining
      appropriate information to satisfy either system is noted. Ancillary information
      for classification of neuroblastoma and related neoplasms is also presented.

PMID- 9533747
TI  - Handling and evaluation of pediatric renal tumors.
AB  - Optimal pathologic evaluation of pediatric renal tumors, which share many
      features in common with their adult counterparts, also includes some relatively
      unique considerations, in large part related to specialized classification,
      grading or staging systems, and ongoing collaborative clinical and biologic
      studies. Important factors in the gross evaluation, procurement of tissue for
      special studies, and selection of tissue blocks for light microscopy are briefly
      reviewed.

PMID- 9533748
TI  - Pathologic evaluation of pediatric soft tissue tumors.
AB  - The subject of soft tissue tumors in children has some parallels with the same
      topic in adults, but many of the details clearly establish the existence of
      distinct differences. Most soft tissue tumors in adults arise in the extremities
      or in the superficial and deep soft tissues elsewhere in the body, and most
      tumors are neoplastic, whether they are benign or malignant. In children, some of
      the most common soft tissue tumors may not be neoplastic at all, but rather are
      malformations of the supporting mesenchymal tissues. There is a common
      classification of soft tissue tumors that is applicable to both pediatric- and
      adult-type neoplasms. Although some of the "adult"-type soft tissue tumors may
      occur in children, the reverse situation is very uncommon. Because pediatric soft
      tissue tumors are not seen with any regularity by many pathologists in a practice
      dominated by adult cases, there is less familiarity and more uncertainty about
      these tumors in children. The differential diagnosis of a malignant soft tissue
      tumor in a child encompasses the broad morphologic spectrum of spindle cells,
      round cells, or combined-pattern neoplasms. The diagnostic process is complex and
      may necessitate an array of ancillary studies, including immunohistochemistry,
      electron microscopy, and molecular diagnostics. After a decision is reached to
      excise a soft tissue sarcoma in a child, many of the steps in the examination of
      the specimen and the reporting of results for diagnostic and staging purposes are
      similar to those in the evaluation of a soft tissue sarcoma in an adult. However,
      it is important for the pathologist and other members of the multidisciplinary
      health care team to remember that a soft tissue tumor in a child may have genetic
      implications that directly influence the care of the patient and the family and
      for which the excised tissue offers a potentially invaluable resource for future
      studies.

PMID- 9533749
TI  - The pathologic handling of skeletal tumors.
AB  - Because bone harbors a wide variety of benign and malignant pathologic entities,
      most of which are uncommon, pathologists feel uneasy when faced with many of
      these lesions. Accurate diagnoses of these lesions require correlation of the
      radiologic and clinical findings with the pathologic features. At the time of
      biopsy, placing a lesion into one of five pathologic groups based on the
      predominant cell or matrix type present (osteoid, chondroid, giant cell, fibrous,
      small cell) aids in analyzing the specimen. Current management of malignant bone
      tumors includes diagnosis on often tiny biopsy samples followed by preoperative
      chemotherapy and finally limb-sparing resection of the involved bone. Adequate
      evaluation of these resections requires extensive examination with grading of the
      tumor necrosis and careful attention to the resection margins.

PMID- 9533750
TI  - An approach to handling pediatric liver tumors.
AB  - Tumors and pseudotumors of the liver account for fewer than 2% of the tumors in
      children and vary considerably in incidence throughout the pediatric age range,
      with hepatoblastoma, infantile hemangioendothelioma, and mesenchymal hamartoma
      seen most frequently in the first 2 years of life and hepatocellular carcinoma,
      focal nodular hyperplasia, and undifferentiated "embryonal" sarcoma noted in
      older children. Despite the variety of malignant tumors seen in children and the
      number of patterns in individual tumors (eg, hepatoblastoma), the most important
      criterion for long-term prognosis is the stage of the tumor at the time of first
      resection. Accurate staging by the surgeon and pathologist is therefore the
      primary objective in examination of malignant hepatic tumors.

PMID- 9533751
TI  - An approach to handling pediatric thyroid and adrenal tumors excluding
      neuroblastoma.
AB  - Thyroid and adrenal tumors, excluding neuroblastoma, are infrequent in children.
      Because of the problems involved in applying diagnostic and prognostic criteria
      developed for adult tumors to pediatric tumors, proper diagnosis of thyroid and
      adrenal tumors in pediatric patients and proper patient management require close
      collaboration on the part of clinicians, surgeons, and surgical pathologists. In
      view of that fact, an approach to handling thyroid and adrenal tumors is
      presented. Special attention is paid to the following aspects of managing both
      types of tumors: procedure, fine-needle aspiration, intraoperative consultation
      (frozen sections), gross examination, histologic examination, special studies,
      diagnosis, and prognostic features.

PMID- 9533752
TI  - Germ cell tumors.
AB  - Germ cell tumors in children are different from those in adults and often differ
      from each other in the site of the tumor and the age of the child. The
      appropriate gross examination and processing of these tumors by pathologists are
      described, and differences according to site and/or age are highlighted. Useful
      special studies such as immunohistochemistry and cytogenetics are identified, and
      the appropriate methods for processing material for these studies are discussed.
      Handling of small biopsy specimens or fine-needle aspirates is also addressed.
      Staging of germ cell tumors by site according to Pediatric Oncology Group and
      Children's Cancer Study Group treatment protocols and the most recent adaptation
      of grading of immature teratomas are outlined.

PMID- 9533753
TI  - Comparative analysis of histology, DNA content, p53 and Ki-ras mutations in
      colectomy specimens with long-standing ulcerative colitis.
AB  - Neoplastic progression in patients with chronic ulcerative colitis is
      characterized by the development of epithelial dysplasia, which is accompanied by
      genetic alterations. This study determined the time of onset of p53 and Ki-ras
      mutations as well as DNA aneuploidy during histological progression towards
      carcinoma. In all, 278 samples of 7 colectomy specimens were analyzed by flow
      cytometry, histology and single-strand conformation polymorphism analysis. Of the
      samples, 22% (61/278) were dysplastic and 43% (122/278) aneuploid, while 25%
      (71/278) showed p53 and 4% (11/278) Ki-ras mutations. The correlation between
      aneuploid status and p53 mutations varied among the patients. A strong
      correlation was noticed between histological progression from low-grade dysplasia
      to carcinoma and p53 mutations as well as DNA aneuploidy. Ki-ras mutations were
      found in 40% (2/5) of the carcinomatous samples. The correlation between p53
      mutations and the histological status of the samples suggest the involvement of
      this genetic event in the development of colon cancer in patients with ulcerative
      colitis. In contrast to Ki-ras mutations, the appearance of p53 mutations is an
      early event. Therefore p53 analysis might be helpful in the classification of
      indefinite dysplasia and in the identification of patients at risk for cancer
      development. Further studies are necessary to detect the additional genetic
      alterations preceding the development of DNA aneuploidy.

PMID- 9533754
TI  - Diet and squamous-cell cancer of the oesophagus: a French multicentre case
      control study.
AB  - An increasing number of reports suggest that diet has an impact on oesophageal
      cancer risk in Western countries, where alcohol and tobacco are held to be the
      major determinants of the risk. The aim of our study was to identify dietary
      factors influencing the risk of oesophageal cancer in France and to determine
      whether certain of these could explain some of the geographical variations. We
      conducted a multicentre case-control study in 3 regions expected to have
      different diet and drinking habits (Normandy, Burgundy and Midi Pyrenees). Two
      hundred eight cases and 399 controls, all males, were interviewed about their
      eating, drinking and smoking habits. After proper adjustment for drinking and
      smoking, high consumption of butter and low consumption of fresh fish, vegetables
      and fruits were associated strongly and independently with an increase in
      oesophageal-cancer risk. Consistently, cholesterol appeared as a risk factor and
      vitamin E, vitamin D and phosphorus as independent protective factors. The
      protective effect of citrus and other fresh fruits (vitamin C) was confined
      strictly to heavy drinkers. Our findings suggest that more than one-third of the
      high incidence of oesophageal cancer in northwest France could be explained by
      the local excess in butter consumption, whereas geographical variations in
      consumption of dietary protective factors could explain no more than 10% of it.
      Overall, a large proportion (57%) of the excess incidence of oesophageal cancer
      in northwest France could be explained by local dietary habits, e.g., drinking
      hot Calvados liquor and excessive consumption of butter.

PMID- 9533755
TI  - TP53 genetic alterations in head-and-neck carcinomas from Brazil.
AB  - In this study we investigated the incidence of mutations and loss of
      heterozygosity (LOH) of the TP53 gene in DNA samples from paired tumor and
      adjacent normal tissue from 90 patients with untreated squamous-cell carcinoma of
      the head and neck. Evidence for TP53 mutations were demonstrated in 53% (48/90)
      of the cases analyzed. All cases were also examined for loss of heterozygosity,
      using a PCR-based polymorphic marker at TP53. LOH was found in 36 out of 72 (50%)
      informative cases. Direct sequencing of PCR products was performed in 45 cases
      with evidence of mutations. The sequencing results revealed the presence of base
      substitutions (67%), deletions (29%) and insertions (4%). Of the base
      substitutions, 70% were transitions and 30% were transversions. Demographic
      variables, tumor site, stage (TNM), family history of cancer, lymph-node
      involvement and histological grade were not important predictors of TP53
      mutations. Nor did TP53 genetic alterations correlate with survival status. In
      conclusion, we show that TP53 genetic alterations are frequent in head-and-neck
      tumors, but are not associated with clinicopathological variables or disease
      progression. Our study provides an evaluation of the spectrum of TP53 mutations
      in the pathogenesis of head-and-neck carcinoma in Brazil.

PMID- 9533756
TI  - An increased risk of cervical intra-epithelial neoplasia grade II-III among human
      papillomavirus positive patients with the HLA-DQA1*0102-DQB1*0602 haplotype: a
      population-based case-control study of Norwegian women.
AB  - Several recent studies have reported different associations between HLA
      specificities and human papillomavirus (HPV)-associated disease of the cervix. We
      report the distribution of DQA1 and DQB1 genes and HPV infection in a population
      based case-control study including 92 patients with histologically verified
      cervical intraepithelial neoplasia grade II-III (CIN II-III) (thus including
      moderate and severe dysplasia and carcinoma in situ) and 225 control subjects. We
      found an overrepresentation of the DQA1*0102-DQB1*0602 haplotype among HPV
      positive cases compared with controls. The association was even stronger when
      comparing HPV-16-positive cases with HPV-16-positive controls. In addition, among
      HPV-16-positive individuals, we observed a decreased frequency of DQA1*0102
      DQB1*0604 in cases compared with controls. We were not able to detect any
      association between CIN II-III and DQB1*03. Compared with previous findings in
      cervical cancer, our data indicate that carrying the DQA1*0102-DQB1*0602
      haplotype gives an increased risk of developing CIN when infected with HPV-16,
      without influencing progression to cancer.

PMID- 9533757
TI  - Leptin in relation to prostate cancer and benign prostatic hyperplasia.
AB  - The aim of our study was to determine whether leptin, a hormone implicated in
      both energy-balance and reproductive function, is involved in the etiology of
      prostate cancer or benign prostatic hyperplasia (BPH). We compared the serum
      leptin levels of 43 cases of incident prostate cancer, 41 patients with BPH, and
      48 healthy controls, all recruited in Athens, Greece. Multiple logistic
      regression modeling was used, with adjustment for age, height, body mass index,
      education, estradiol, testosterone, dihydrotestosterone, dehydroepiandrosterone
      sulfate, sex hormone-binding globulin and insulin like growth factor 1. Odds
      ratios per 4 ng/ml increment of leptin were 0.70 [95% confidence interval (CI)
      (0.32,1.55)] for prostate cancer and 1.06 [95% CI (0.67,1.67)] for BPH. After
      adjustment for body mass index, serum leptin levels were not significantly
      correlated with levels of any of the other hormones under study. Leptin levels
      are unlikely to affect the risk of either prostate cancer or BPH substantially.

PMID- 9533758
TI  - Body size in different periods of life and breast cancer risk in post-menopausal
      women.
AB  - Adult obesity has been associated with an increased risk of post-menopausal
      breast cancer, but it is unclear whether this relationship reflects a causal role
      of obesity during childhood and adolescence, of weight gain during adult life or
      of adult obesity per se. In a population-based case-control study in all of
      Sweden, we included 3,345 (84% of all eligible) women aged 50-74 years with
      invasive breast cancer, and 3,454 (82% of all selected) controls of similar age.
      Mailed questionnaires and telephone interviews were used to collect detailed
      information on anthropometric measures. Odds ratios were estimated through
      multiple logistic regression. Women with the leanest somatotype at age 7 had
      about a 3-fold higher risk of breast cancer than the most obese (P for trend
      0.0009). A suggested protective effect of a high body mass at age 18 and a
      detrimental influence of body mass 1 year prior to data collection largely
      reflected the effect of weight gain after age 18, a strong predictor of breast
      cancer risk. Among women at least 20 years post menopause, those who had gained
      30 kg or more since age 18 had an odds ratio of 2.04 (95% confidence interval
      1.20-3.48) of breast cancer compared with those who had maintained their weight
      unchanged. The effect of weight gain was unequivocal among non-users but not
      among users of hormone replacement therapy. Our findings have important
      implications, suggesting weight preservation as a means for prevention of post
      menopausal breast cancer as well as a causal role of childhood body build in
      breast cancer etiology.

PMID- 9533759
TI  - Protective effect of fruits and vegetables on stomach cancer in a cohort of
      Swedish twins.
AB  - Observational studies, primarily of a case-control design, have shown an inverse
      association of fruit and vegetable consumption with the risk of stomach cancer, a
      finding tentatively attributed to anti-oxidant vitamins. Ensuing randomized
      intervention trials of these vitamins, however, have been mostly negative.
      Therefore, the seemingly protective effect of fruit and vegetables in case
      control studies is suspected to be influenced by the information bias inherent in
      the retrospective assessment of exposure, particularly since pre-conceptions
      about the wholesome effects of these foods are common among the public. Our aim
      was to examine the association of fruit and vegetable intake with the risk of
      stomach cancer in a prospective cohort study. Fruit and vegetable consumption was
      assessed in 1967 in 11,546 individuals in the Swedish Twin Registry, along with a
      wide range of potentially confounding factors. Complete follow-up through 1992
      was attained through record linkage to the National Cancer and Death Registers.
      The relative risk of stomach cancer was estimated in proportional hazards models,
      with confidence intervals (CIs) adjusted for correlated outcomes. The risk of
      stomach cancer was inversely related to fruit and vegetable consumption.
      Controlling for potentially confounding factors, the relative risk among subjects
      with the lowest compared to those with the highest intake was 5.5 (95% CI 1.7
      18.3) with a statistically significant dose-risk trend (p < 0.05). Our results
      indicate that information bias is not likely to explain the discrepancy between
      the results of observational studies and of randomized-intervention trials.

PMID- 9533760
TI  - Goralatide (AcSDKP), a negative growth regulator, protects the stem cell
      compartment during chemotherapy, enhancing the myelopoietic response to GM-CSF.
AB  - The aim of our study was to investigate the protection afforded to the bone
      marrow by Goralatide (AcSDKP), an inhibitor of hemopoietic stem cell
      proliferation, when administered alone or in combination with a growth factor
      (granulocyte/macrophage colony-stimulating factor [GM-CSF]) during iterative
      cycles of Ara-C (cytarabine) treatment. In control mice receiving the inhibitor
      alone without Ara-C, the number of granulocytes was reduced during treatment, and
      a surge in number of peripheral blood cells was observed after its completion.
      Peripheral hematological responses were monitored during 3 consecutive cycles of
      Ara-C chemotherapy and the resultant nadir and recoveries. Analysis of variance
      of the treatment effects pooled over the 3 cycles showed that a treatment regimen
      in which the inhibitor was administered during the myelotoxic periods of
      chemotherapy confirmed the existence of a surge after completion of
      administration of the inhibitor and showed a significant protective effect. When
      the cycles of chemotherapy plus Goralatide were followed by GM-CSF, the recovery
      from leukopenic nadirs was accelerated and the white blood cells and granulocyte
      levels were markedly increased over those observed in control mice and in mice
      treated either with Goralatide alone or with GM-CSF alone. The differences were
      highly significant. A consistent and significant increase (p < 0.001) in platelet
      count was also noted in animals given Goralatide in conjunction with Ara-C or Ara
      C + GM-CSF. After three treatment cycles, this response to the CSF was far better
      in mice treated by the inhibitor than when CSF was given alone, suggesting a
      protection of the stem cell pool.

PMID- 9533761
TI  - Comparative study on the induction of cytostasis and apoptosis by ICI 182,780 and
      tamoxifen in an estrogen receptor-negative ovarian cancer cell line.
AB  - We have compared the effects of a broad range of clinically relevant
      concentrations (0.1 to 10 microM) of the steroidal pure anti-estrogen ICI 182,780
      and the non-steroidal partial anti-estrogen tamoxifen (TAM) on cell proliferation
      and induction of apoptosis in the estrogen receptor (ER)-negative ovarian
      carcinoma cell line A2780. Cell proliferation was assessed by evaluating the
      number of viable cells, changes in cell-cycle distribution and cell replication
      rate; while apoptosis induction was assessed by examining nuclear morphological
      changes associated with apoptotic death and DNA cleavage into 300 and 50 kbp
      units (large DNA fragmentation) and into 180 bp units (internucleosomal DNA
      fragmentation). We provide evidence that 0.1 to 10 microM ICI 182,780 and TAM
      significantly inhibit the growth of A2780 cells in a dose-dependent fashion.
      Cytokinetic analysis revealed that only 10 microM TAM caused a significant
      blockade in G1 and a diminished replication rate. Conversely, we show that 0.1 to
      10 microM ICI 182,780 and TAM induce apoptosis in a dose-dependent fashion. The
      earliest recognizable apoptotic change induced by treating the cells with these 2
      drugs was DNA cleavage into 300 and 50 kbp units. This started to be visible in
      adherent cells, implying that apoptosis induction by ICI 182,780 and TAM was not
      determined by the loss of cell-substrate interaction. A further degradation of
      300 and 50 kbp DNA fragments occurred in cells that had lost their adhesion to
      the culture plate. We observed the ladder pattern typical of internucleosomal DNA
      cleavage by treating A2780 cells with the highest dose (10 microM) of ICI 182,780
      and TAM. Lower concentrations of these 2 drugs (0.1 to 1 microM) did not produce
      such a pattern of DNA fragmentation. Typical features of apoptotic nuclei were
      detectable after both drug treatments. However, cells undergoing apoptosis
      induced by ICI 182,780 showed hyper-aggregation of chromatin, whereas TAM-treated
      cells preferentially exhibited chromatin clumping.

PMID- 9533762
TI  - Transport of glutathione conjugates into secretory vesicles is mediated by the
      multidrug-resistance protein 1.
AB  - Intracellular glutathione-conjugate transport was evaluated in the human small
      cell lung carcinoma cell line GLC4 with low multidrug resistance protein (MRP1)
      expression and its 300x doxorubicin-resistant, MRP1-over-expressing, GLC4-Adr
      subline. Transport of non-toxic concentrations of monochlorobimane and 5-chloro
      methyl fluorescein diacetate was evaluated using fluorescence microscopy. After
      exposure to these compounds, fluorescence was observed especially in
      intracellular vesicles in GLC4-Adr. Immunotransmission electron microscopy showed
      that MRP1 was present in the vesicle membranes and plasma membrane, while inside
      the vesicles the glutathione conjugate of 1-chloro-2,4-dinitrobenzene could be
      detected. Experiments with brefeldin A, which induces arrest in vesicle release
      from the Golgi complex, indicated that these vesicles may originate from the
      trans-Golgi network. In GLC4-Adr cells, doxorubicin also was transported in
      vesicles, with an arrest in vesicle release from the Golgi complex. Our results
      indicate that MRP1 functions as a glutathione-conjugate transporter not only at
      the plasma membrane but also in intracellular secretory vesicles.

PMID- 9533763
TI  - Integrin alpha3beta1-mediated interaction with laminin-5 stimulates adhesion,
      migration and invasion of malignant glioma cells.
AB  - Gliomas, characterized by their progressively invasive phenotype, express
      integrin alpha3beta1 as a major receptor for the extracellular matrix both in
      vivo and in vitro. Since the integrin alpha3beta1 has been shown to be a specific
      receptor for laminin-5 (alpha3beta3gamma2), we examined the effects of purified
      human laminin-5 on adhesion, migration and invasion of human glioma cells. Among
      different types of laminin variants and other matrix proteins including
      fibronectin and vitronectin, laminin-5 was most potent in promoting adhesion and
      migration of different kinds of glioma cells. Laminin-5-mediated adhesion and
      migration were specifically inhibited by monoclonal antibodies against integrin
      alpha3 and beta1 chains, confirming the role of integrin alpha3beta1 as the major
      laminin-5 receptor. Invasion of the reconstituted basement membrane (i.e.,
      Matrigel) by glioma cells was also selectively stimulated by laminin-5. Out
      results show that laminin-5 is the major extracellular stimulant for glioma cell
      adhesion, migration and invasion. The immunohistochemical distribution of laminin
      gamma2 chain, a laminin subunit unique to laminin-5, showed that it was expressed
      in the tumor parenchyma of human glioma tissues. Expression of laminin alpha3,
      beta3 and gamma2 chains in glioma tissues and in glioma cell lines was also
      demonstrated at the messenger RNA level by reverse transcription polymerase chain
      reaction. Our results, taken together, show that laminin-5 may be involved in the
      invasive phenotype of malignant gliomas both in vitro and in vivo.

PMID- 9533764
TI  - Attenuation by methionine of monochloramine-enhanced gastric carcinogenesis
      induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats.
AB  - Helicobacter pylori appears to play a major role in the development of gastric
      cancer in humans. The mechanism behind the carcinogenic or co-carcinogenic
      effects of H. pylori has not been established. Ammonia, generated by urea from H.
      pylori, has been studied as a possible cause. However, the ammonia-monochloramine
      system has been shown to play a more important role in H. pylori-associated
      mucosal injury. Therefore, the effects of combined administration of
      monochloramine and methionine, singly or together, on the development of gastric
      cancers induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) were investigated
      in inbred Wistar rats. After receiving oral MNNG and regular chow pellet for 25
      weeks, rats received regular chow pellets or chow pellets containing 20% ammonium
      acetate, and normal tap water or water containing 30 mM sodium hypochlorite, with
      or without a subcutaneous injection of methionine, until the end of the
      experiment (week 52). Treatment with both ammonium acetate and sodium
      hypochlorite, which produce monochloramine, significantly increased the incidence
      of gastric cancers in week 52, whereas the concomitant administration of
      methionine with ammonium acetate and sodium hypochlorite significantly attenuated
      such enhanced gastric carcinogenesis. Spectrophotometric examination revealed
      that methionine scavenged monochloramine. Our findings suggest that H. pylori
      associated gastric carcinogenesis may be mediated by monochloramine.

PMID- 9533765
TI  - Laminin and estradiol regulation of the plasminogen-activator system in MCF-7
      breast-carcinoma cells.
AB  - We have investigated the effects of laminin, on the plasminogen-activator system
      of MCF-7 breast-carcinoma cells. MCF-7 cells were incubated on plastic or laminin
      coated wells, and medium and cell lysate aliquots were assayed for tissue-type
      (tPA) and urokinase-type plasminogen activator (uPA) by a chromogenic assay in
      combination with anti-uPA antibodies. Cells cultured on laminin displayed a 5
      fold increase in tPA activity and a 2-fold decrease in uPA activity relative to
      cells on plastic. These effects could be mimicked by laminin fragment P1 but not
      by collagen I or fibronectin. tPA activity of cells treated with estradiol (10
      nM) was 3-fold higher, that of cells on laminin treated with estradiol was 15
      fold higher, than that of control. Northern-blot analysis showed that tPA mRNA
      levels were up-regulated by estradiol and laminin, whereas PAI-1 mRNA levels were
      down-regulated by laminin and not affected by E2. Concomitant treatment with
      laminin and estradiol, decreased PAI-1 mRNA and increased tPA mRNA levels,
      accounting for the synergistic increase in tPA activity. Laminin exerted only a
      modest (approx. 2-fold) inhibitory effect on uPA mRNA levels. In the breast
      carcinoma cell line MDA-MB-231, down-regulation of PAI-1 and uPA mRNA by laminin
      was not observed. Adhesion assays indicated that alpha2beta1 is the predominant
      receptor for laminin in MCF-7 cells. MDA-MB-231 cells expressed alpha2 (54%) but
      this integrin is not used as a laminin receptor. These results support a role for
      alpha2beta1 in mediating interactions of MCF-7 with LN.

PMID- 9533766
TI  - 2-Deoxyglucose inhibits chemotherapeutic drug-induced apoptosis in human
      monocytic leukemia U937 cells with inhibition of c-Jun N-terminal kinase 1/stress
      activated protein kinase activation.
AB  - Human monocytic leukemia U937 cells undergo apoptosis when treated with antitumor
      drugs, such as etoposide, camptothecin and mitomycin C. The molecular mechanism
      of the drug-induced apoptosis is not well understood. In this study, we found
      that 2-deoxyglucose (2DG), an analog of D-glucose and an inducer of glucose
      regulated stress, inhibited anticancer drug-induced but not tumor necrosis factor
      alpha-induced apoptosis of U937 cells. 2DG did not reduce initial cellular damage
      caused by etoposide, an inhibitor of topoisomerase II, suggesting that 2DG
      affected subsequent cellular responses involved in apoptosis. 2DG inhibited the
      etoposide-induced activation of c-Jun N-terminal kinase 1/stress-activated
      protein kinase (JNK1/SAPK) and the subsequent activation of CPP32, both of which
      are positive regulators for etoposide-induced apoptosis of U937 cells. Our
      results indicate that 2DG inhibits apoptosis by blocking the signals from
      cellular DNA damage for JNK1/SAPK activation.

PMID- 9533767
TI  - De novo expression of the alpha5beta1-fibronectin receptor in HT29 colon-cancer
      cells reduces activity of C-SRC. Increase of C-SRC activity by attachment on
      fibronectin.
AB  - Changes in integrin expression during malignant transformation have been observed
      in many tumors. Colon-carcinoma cells show reduced expression or even loss of the
      alpha5beta1 integrin compared to normal or adenoma cells. To determine the
      significance of absent alpha5beta1 integrin signaling, we transfected the cDNA
      coding for the alpha5 integrin sub-unit into the human colon-carcinoma cell line
      HT29, which constitutively lacks this subunit but does express the beta1 subunit.
      We show here that the newly expressed fibronectin receptor alpha5beta1 generates
      multiple signals, causing marked changes in cytoskeletal arrangements within a
      few minutes of adhesion to fibronectin. Cells expressing the alpha5beta1 integrin
      exhibit the formation of actin stress fibers and focal adhesions, as well as the
      induction of tyrosine phosphorylation of several proteins, within 10 min. We
      identified the focal adhesion kinase pp125FAK and the cytoskeletal protein
      paxillin as major phosphorylation substrates in these cells. These proteins
      remained hypophosphorylated when alpha5-negative control cells were plated on
      fibronectin. The tyrosine kinase pp60c-src, regarded as central in the regulation
      of cellular proliferation and constitutively over-expressed in HT29 and in colon
      carcinoma cells, showed reduced intrinsic kinase activity in unstimulated
      HT29alpha5 cells. In contrast, fibronectin-induced signaling through alpha5beta1
      increased pp60c-src activity. Moreover, immunoprecipitation of pp60c-src from
      extracts of HT29alpha5 cells cultivated on fibronectin for 20 min revealed
      complex formation of pp60c-src and tyrosine-phosphorylated pp125FAK. Our data
      suggest that de novo expression of the alpha5beta1 integrin in HT29 colon-cancer
      cells restores signaling via pp125FAK and pp60c-src. Thus, loss of this receptor
      during malignant transformation may contribute to tumor-cell autonomy, while
      reduced activity of pp60c-src in HT29alpha5-cells may participate directly in
      growth control.

PMID- 9533769
TI  - Chemosensitivity of solid tumor cells in vitro is related to activation of the
      CD95 system.
AB  - We have identified the CD95 system as a key mediator of chemotherapy-induced
      apoptosis in leukemia and neuroblastoma cells. Here, we report that sensitivity
      of various solid tumor cell lines for drug-induced cell death corresponds to
      activation of the CD95 system. Upon drug treatment, strong induction of CD95
      ligand (CD95-L) and caspase activity were found in chemosensitive tumor cells
      (Hodgkin, Ewing's sarcoma, colon carcinoma and small cell lung carcinoma) but not
      in tumor cells which responded poorly to drug treatment (breast carcinoma and
      renal cell carcinoma). Blockade of CD95 using F(ab')2 anti-CD95 antibody
      fragments markedly reduced drug-induced apoptosis, suggesting that drug-triggered
      apoptosis depended on CD95-L/receptor interaction. Moreover, drug treatment
      induced CD95 expression, thereby increasing sensitivity for CD95-induced
      apoptosis. Drug-induced apoptosis critically depended on activation of caspases
      (ICE/Ced-3-like proteases) since the broad-spectrum inhibitor of caspases zVAD
      fmk strongly reduced drug-mediated apoptosis. The prototype substrate of
      caspases, poly(ADP-ribose) polymerase, was cleaved upon drug treatment,
      suggesting that CD95-L triggered autocrine/paracrine death via activation of
      caspases. Our data suggest that chemosensitivity of solid tumor cells depends on
      intact apoptosis pathways involving activation of the CD95 system and processing
      of caspases. Our findings may have important implications for new treatment
      approaches to increase sensitivity and to overcome resistance of solid tumors.

PMID- 9533768
TI  - Sulindac sulfide alters the expression of cyclin proteins in HT-29 colon
      adenocarcinoma cells.
AB  - Sulindac sulfide (SS), the active metabolite of the colon cancer chemopreventive
      compound sulindac, inhibits the proliferation of HT-29 colon cancer cells mainly
      by inducing cell quiescence. We determined by bivariate flow-cytometric analysis
      both the DNA and cyclin protein content of individual cells. Thus, we assessed in
      detail the expression of several cyclins during the cell-cycle phases and
      demonstrated that SS (i) decreases the expression of cyclins B1 and E and (ii)
      increases the expression of cyclins D1, D2 and D3, particularly in the G1 phase
      of the cell cycle. SS-induced apoptotic cells expressed both E- and D-type
      cyclins but not cyclin B1. The changes in cyclin expression combined with reduced
      catalytic activity of cyclin-dependent kinases could explain in molecular terms
      the anti-proliferative effect of SS on HT-29 colon cancer cells. These changes
      may contribute to the chemopreventive effect of sulindac.

PMID- 9533770
TI  - Interleukin-2 gene therapy of surgical minimal residual tumour disease.
AB  - Our study was designed to examine the effects of IL-2 gene therapy in a surgical
      minimal residual tumour disease (SMRTD). Mice were inoculated s.c. with
      methylcholanthrene (MC)-induced MC12 sarcoma cells. When the tumours reached 8 to
      12 mm in diameter, they were excised, either completely ("microscopic SMRTD") or
      incompletely ("macroscopic SMRTD"). On day 90 after surgery, the tumour
      recurrence rate in untreated mice with microscopic SMRTD was approximately 30%,
      whereas in those with macroscopic SMRTD it was 75%. After surgery, experimental
      mice were treated with 2 types of irradiated, IL-2 gene-modified, IL-2-producing
      tumour cell vaccine. One type of vaccine was derived from the MC12 sarcoma cells
      (MC12-1L2/IV-3); the other type was derived from an unrelated X63-Ag8.653
      plasmacytoma (X63-m-IL-2). Both types of vaccine failed to cure the macroscopic
      SMRTD. Whereas the X63-m-IL-2 vaccine was also ineffective in the microscopic
      SMRTD, the MC12-IL2/IV-3 vaccine was capable of preventing growth in all but one
      mouse (1164) with microscopic SMRTD when administered 2 to 5 days after surgery.
      If the vaccination took place 2 days before surgery or later than 5 days after
      surgery, the therapeutic activity was lost. Vaccination with irradiated parental
      MC12 cells did not produce any significant benefit compared to the operated-only
      mice. The protective effect of the MC12-L2/IV-3 vaccine was specific and
      comparatively long-lasting. Vaccinated mice, which had rejected the MC12 tumour
      residuum, were capable of rejecting a second inoculum of the MC12 sarcoma cells
      injected on days 35 to 110 after surgery but succumbed to the growth of 2 other
      unrelated murine sarcomas carrying different tumour-rejection antigens.

PMID- 9533771
TI  - Autocrine motility factor and the extracellular matrix. I. Coordinate regulation
      of melanoma cell adhesion, spreading and migration involves focal contact
      reorganization.
AB  - Cellular interactions with the extracellular matrix are complex and are involved
      in numerous biological processes. These interactions may be modulated by
      cytokines such as tumor cell autocrine motility factor, a secreted molecule that
      regulates cellular growth and migration by a receptor-mediated pathway. In this
      report we provide evidence suggesting that high- and low-metastatic K1735
      melanoma cells coordinate their attachment, spreading and migratory responses to
      autocrine motility factor and the extracellular substratum through alterations in
      focal adhesion plaque architecture that are dependent on both inherent cellular
      metastatic phenotype and the composition of the supporting matrix. Thus, since
      activation of the autocrine motility factor receptor has previously been shown to
      enhance the experimental metastasis of the high- but not the low-metastatic K1735
      cells, differences in melanoma cell malignancy in this system may be due in part
      to a coordinated interplay between cytokine-mediated responses and extracellular
      matrix-directed regulation of cellular adhesion, spreading and motility.

PMID- 9533772
TI  - Autocrine motility factor and the extracellular matrix. II. Degradation or
      remodeling of substratum components directs the motile response of tumor cells.
AB  - Autocrine motility factor is a tumor-secreted cytokine which regulates cellular
      growth and motility by a receptor-mediated pathway. In the accompanying report
      (Part I of II), it was demonstrated that high (K1735-M1) and low (K1735-C1.11)
      metastatic murine melanoma cells display distinct adhesion and spreading
      characteristics which correlate with their differential spontaneous and
      stimulated migrations on the extracellular matrix components fibronectin, laminin
      and collagen IV. These parameters were further related to discrete profiles of
      focal adhesion plaque integrity and reorganization. Here we describe unique
      migration patterns observed in these murine melanoma cells which reflect
      differences in degradation and/or remodeling of the cellular substratum. These
      profiles of matrix interaction were influenced distinctly by autocrine motility
      factor and dictated by both substrate composition and cellular phenotype. Since
      activation of the autocrine motility factor receptor stimulates invasion of a
      reconstituted basement membrane and enhances experimental metastasis by high- but
      not low-metastatic K1735 cells, differences in the invasive phenotypes of these
      cells may be due in part to their differential responses to external stimuli
      coupled with internal propensities toward either matrix degradation and migration
      (high-metastatic cells) or matrix remodeling and stasis (low-metastatic cells).

PMID- 9533773
TI  - Detection of a potential receptor for the H-blood-group antigen on rat colon
      carcinoma cells and normal tissues.
AB  - Up-regulation of the synthesis of carbohydrate tumor-associated antigens
      terminated by the disaccharide Fucalpha1-2Gal is frequent in colon carcinoma and
      associated with poor prognosis. There is evidence that Fucalpha1-2Gal (H
      disaccharide) structures increase cancer-cell motility and tumorigenicity by as
      yet unknown mechanisms. Using polyacrylamide-based neoglycoconjugates, we looked
      for a potential receptor for this disaccharide, and observed that a
      neoglycoconjugate probe containing the H-disaccharide could bind rat colon
      carcinoma cells in a dose-dependent manner, whereas very little binding was
      evidenced when a probe containing glucose was used. Binding of the H-disaccharide
      probe could be inhibited by the free H-disaccharide as well as by unlabeled
      neoglycoconjugates containing a terminal H-disaccharide. The best inhibitor was
      the H-type-1 trisaccharide neoglycoconjugate. Histochemical detection of the
      potential H-receptor was performed on rat normal tissues and in situ 1,2
      dimethylhydrazine-induced colon carcinomas. A strong binding of the H
      disaccharide probe was evidenced on most tumors that could be partly inhibited by
      the trisaccharide Fucalpha1-2Galbeta1-4Glc and by the unlabeled H-disaccharide
      neoglycoconjugate, indicating carbohydrate specificity of the binding. Staining
      of normal colonic mucosa was much weaker. Strong staining was also observed on
      some normal tissues, such as the spleen or lymph nodes, while others, such as
      lungs or liver, were negative. Probes containing glucose or the Lewis-a
      trisaccharide did not stain tumors or normal tissues. These results provide
      preliminary evidence for the existence of H-specific binding sites, the number of
      which increases in colon carcinoma.

PMID- 9533774
TI  - Growth dependency of a new human pancreatic cancer cell line, YAPC, on autocrine
      interleukin-1alpha stimulation.
AB  - We established a new human pancreatic cancer cell line from the malignant ascites
      of a patient with pancreatic cancer and called it YAPC. Cytogenetic and
      morphological analysis indicated that this cell line is monoclonal and of human
      origin. YAPC cells grow in nude mice, resulting in the formation of a tumor with
      some functional characteristics of the original tumor. The cells secreted a large
      amount of inflammatory cytokines including interleukin-1alpha(IL-1alpha), IL-6
      and IL-8 in the culture medium. Removal of serum from the culture medium did not
      change the growth rate of YAPC cells, but the removal of the conditioned medium
      arrested their proliferation under the serum-free conditions. Exogenous IL-1alpha
      but neither IL-6 nor IL-8 stimulated DNA synthesis of the cells and accelerated
      the progress of cell cycle from G1 to the S phase. Anti-IL-1alpha antibody
      prevented growth of the cells in a dose-dependent fashion. In this pancreatic
      cancer cell line cell growth is dependent on IL-1alpha in an autocrine fashion.
      This line may be a useful model for studying growth regulation mechanisms of
      pancreatic cancer.

PMID- 9533775
TI  - Expression of four CEA family antigens (CEA, NCA, BGP and CGM2) in normal and
      cancerous gastric epithelial cells: up-regulation of BGP and CGM2 in carcinomas.
AB  - Four human carcinoembryonic antigen (CEA) family members, CEA (CD66e), non
      specific cross-reacting antigen (NCA, CD66c), biliary glycoprotein (BGP, CD66a)
      and CEA gene-family member 2 (CGM2), are expressed in normal mucosal epithelia of
      the colon. Expression of BGP and CGM2 has recently been demonstrated to be down
      regulated in colorectal adenocarcinomas. We have now investigated the expression
      of the 4 CEA family antigens in gastric adenocarcinoma and carcinoma cell lines
      in comparison with adjacent normal gastric mucosa. The transcripts of the CEA,
      NCA and BGP genes evaluated by reverse transcription-polymerase chain reaction
      were detectable at various levels in all the gastric adenocarcinoma cell lines
      tested, while CGM2 mRNA was detectable in the cell lines of poorly differentiated
      but not of well-differentiated carcinomas. The levels of CEA mRNA in normal
      gastric mucosa were variable but mostly increased in adenocarcinomas. The sparse
      expression of NCA observed in the normal tissues was markedly up-regulated in the
      carcinomas. In contrast to previous findings on normal and cancerous colonic
      tissues, the transcripts of CGM2 were totally undetectable and those of BGP were
      recognized only marginally, if at all, in normal gastric mucosa, while both
      messages were detected at significant levels in most of the gastric
      adenocarcinomas. This was confirmed by in situ hybridization. Our findings
      indicate that expression of the CEA family antigens, particularly that of BGP and
      CGM2, is differently regulated in epithelial cells of the colon and the stomach.

PMID- 9533776
TI  - A potent protein-tyrosine kinase inhibitor which selectively blocks proliferation
      of epidermal growth factor receptor-expressing tumor cells in vitro and in vivo.
AB  - A calculated 3-D model of the kinase domain of the epidermal growth factor
      receptor (EGF-R) protein-tyrosine kinase (PTK) was used to develop a
      pharmacophore model for ATP-competitive inhibitors and, subsequently, a new class
      of selective EGF-R kinase inhibitors. CGP 59326A, a highly selective and potent
      inhibitor of the EGF-R in vitro, inhibited the proliferation of EGF-R-expressing
      epithelial lines, while having little anti-proliferative activity against EGF-R
      negative lines. In contrast to previously described inhibitors, CGP 59326A had
      potent and selective in vivo anti-tumor activity at well-tolerated doses against
      EGF-R-expressing tumors (e.g., ED50 of 0.78 to 1.5 mg/kg for inhibition of A431
      tumor growth). CGP 59326A inhibited growth of human tumor xenografts expressing
      the EGF-R but showed little activity against EGF-R-negative xenografts.
      Combination of CGP 59326A with cytotoxic agents resulted in tumor regression and
      cures. The high selectivity and attractive biological profile of CGP 59326A
      suggest that it could have therapeutic value in the treatment of proliferative
      diseases which involve mitogenic signaling from the EGF-R.

PMID- 9533777
TI  - From dystrophinopathy to sarcoglycanopathy: evolution of a concept of muscular
      dystrophy.
AB  - Duchenne and Becker muscular dystrophies are collectively termed
      dystrophinopathy. Dystrophinopathy and severe childhood autosomal recessive
      muscular dystrophy (SCARMD) are clinically very similar and had not been
      distinguished in the early 20th century. SCARMD was first classified separately
      from dystrophinopathy due to differences in the mode of inheritance. Studies
      performed several years ago clarified some immunohistochemical and genetic
      characteristics of SCARMD, but many remained to be clarified. In 1994, the
      sarcoglycan complex was discovered among dystrophin-associated proteins.
      Subsequently, on the basis of our immunohistochemical findings which indicated
      that all components of the sarcoglycan complex are absent in SCARMD muscles, and
      the previous genetic findings, we proposed that a mutation of any one of the
      sarcoglycan genes leads to SCARMD. This hypothesis explained and predicted
      various characteristics of SCARMD at the molecular level, most of which have been
      verified by subsequent discoveries in our own as well as various other
      laboratories. SCARMD is now called sarcoglycanopathy, which is caused by a defect
      of any one of four different sarcoglycan genes, and thus far mutations in
      sarcoglycan genes have been documented in the SCARMD patients. In this review,
      the evolution of the concept of sarcoglycanopathy separate from that of
      dystrophinopathy is explained by comparing studies on these diseases.

PMID- 9533778
TI  - Presynaptic and postsynaptic mechanisms underlying H-reflex changes produced by a
      selective voluntary contraction.
AB  - Concurrent recordings of (i) the soleus H reflex and (ii) the underlying afferent
      (P1) and efferent (P2) neural volleys were performed during a protracted,
      moderate, isometric, voluntary contraction of the soleus (S) muscle, and the
      subsequent release period. Besides the expected enhancement of the H reflex,
      muscular contraction caused a significant reduction in the corresponding central
      delay (as extrapolated from variations of P1-P2 interval), while the opposite
      trend occurred during the release phase. Control experiments, based on (a) neural
      blockade below the stimulation site, (b) muscle stretching at the end of the
      muscular contraction, (c) changes in amplitude of homonymous and heteronymous S
      responses, and (d) variations in effectiveness of homonymous and heteronymous
      conditioning volleys on the S motoneuronal pool, showed that both voluntary
      contraction and the subsequent release period are associated with a reduced
      effectiveness of la afferents, while postsynaptic motoneuronal responsiveness is
      significantly modified only during the actual contraction time.

PMID- 9533779
TI  - Cyclosporin A in resistant chronic inflammatory demyelinating
      polyradiculoneuropathy.
AB  - The role of cyclosporin A (CsA) in the treatment of resistant chronic
      inflammatory demyelinating polyradiculoneuropathy (CIDP) was retrospectively
      reviewed in 19 patients who had failed to respond adequately to corticosteroids,
      plasmapheresis, intravenous immunoglobulin, and in some cases other
      immunosuppressive agents. Patients were subdivided into progressive or relapsing
      types according to the course of disease and response to therapy graded at follow
      up by clinical and electrophysiological criteria. In the progressive group, the
      mean disability status declined from 3.8+/-0.7 to 1.8+/-1.1 grades on a 5-grade
      scale following CsA therapy (P<0.001). In the relapsing group, the mean annual
      incidence of relapse declined from 1.0+/-0.5 to 0.2+/-0.4 after commencement of
      CsA (P<0.05). Dose-dependent, reversible nephrotoxicity was the most serious
      complication of therapy, and necessitated cessation of CsA in 2 patients. In
      conclusion, CsA is an efficacious and, with appropriate monitoring, safe therapy
      for patients with CIDP.

PMID- 9533780
TI  - Spontaneous and evoked ectopic discharges recorded from single human axons.
AB  - A quantitative assessment was made of the firing characteristics of repetitive
      axonal discharges encountered during microneurographic recordings from human
      peripheral nerves. Spontaneous activity was recorded from 16 single axons using
      tungsten microelectrodes inserted percutaneously into fascicles of the median or
      peroneal nerves in normal subjects. These discharges typically consisted of brief
      bursts of 2-5 spikes occurring at a frequency of 7-10 Hz. Peak instantaneous
      frequencies usually exceeded 300 Hz. Based on their similarity with spontaneous
      high-frequency discharges recorded from single axons following nerve damage,
      ischemia, prolonged electrical stimulation, or hyperventilation, it is concluded
      that they are generated ectopically at the site of a previous impalement of a
      nerve fiber. It is suggested that short-term damage to the nerve fiber caused by
      the microelectrode may allow accumulation of K+ underneath the myelin, triggering
      an inward flow of K+ and regenerative depolarizations. Alternatively, internodal
      channels may be exposed following damage to the myelin, resulting in the
      generation of spontaneous pacemaker potentials and repetitive discharges.

PMID- 9533782
TI  - Stimulated single-fiber electromyography in the rat.
AB  - We constructed an animal model of stimulated single-fiber electromyography
      (SFEMG) by testing Wistar rats under anesthesia. Stimuli of 1 Hz were applied to
      the sciatic nerve through an insulated monopolar needle electrode. Single-fiber
      action potentials were acquired from the gastrocnemius muscle. Jitter was
      assessed by the mean consecutive difference (MCD). Eighty-seven fibers were
      obtained from 12 rats. Their MCDs ranged from 2 to 72 micros (17.7+/-13.4). Seven
      of these values were less than or equal to 5 micros, and three exceeded 50
      micros. Neuromuscular blocking agents injected into some of the rats induced
      considerable increases in jitter and blocking. A rat with one fiber with an MCD
      less than 5 micros also received an injection of curare. The jitter showed the
      same pattern of increment, evidence that the small jitter was not attributable to
      direct muscle stimulation. These results show that SFEMG can be used on rats. In
      addition, jitter reflects the changes in motor end-plate function. The findings
      also suggest the presence of an extremely high safety factor in rat neuromuscular
      junctions.

PMID- 9533781
TI  - Localized and limited changes in the expression of myosin heavy chains in injured
      skeletal muscle fibers being repaired.
AB  - The process of skeletal muscle repair was investigated by immunocytochemical
      evaluation of chicken leg muscles injured by a localized crush or superficial
      cut. Only the damaged parts of the muscle fibers, approximately 400-500 microm
      across, along the longitudinal axis, expressed ventricular myosin heavy chain.
      The level of this myosin heavy chain along the fiber length further decreased
      with time. Unlike the newly generated independent regenerating myotubes, even the
      injured parts of original mature muscle fibers positive for ventricular myosin
      heavy chain in the immediate vicinity of injury did not show changes in the
      expression of slow or fast myosin heavy chains in these regions. It is concluded
      that muscle fibers injured by superficial cut or crush methods used in this study
      despite being multinucleated were rapidly repaired by localized changes without
      affecting the major gene expression in the uninjured parts of the fibers.

PMID- 9533783
TI  - Single muscle fiber analysis of myoclonus epilepsy with ragged-red fibers.
AB  - We examined two muscle biopsy specimens from a proband and her mother with
      myoclonus epilepsy with ragged-red fibers (MERRF), both obtained at an interval
      of about 10 years, using histochemistry, in situ hybridization, and single-fiber
      polymerase chain reaction. Total (wild-type and mutant) mitochondrial DNAs
      (mtDNAs) were greatly increased in ragged-red fibers (RRF) over non-RRF in all
      muscle specimens analyzed. The proportion of mutant mtDNA was also significantly
      higher in RRF than in non-RRF. By comparing the first and second muscle biopsied
      specimens in each patient, we found that while the proportion of RRF, cytochrome
      coxidase deficient fibers, and mutant DNA in muscle changed over a 10-year
      period, the proportion of wild-type and mutant mtDNAs in RRF and in non-RRF was
      similar between the two specimens. These results suggest that the ratio of wild
      type to mutant mtDNAs in RRF and non-RRF in MERRF is at a steady state level in
      each muscle fiber, without replicative advantage of mutant mtDNA.

PMID- 9533784
TI  - Symmetry of normal motor and sensory nerve conduction measurements.
AB  - Nerve conduction measurements in normal subjects are assumed to be symmetric, but
      the normal limits of symmetry have not been determined. Full data on the limits
      of symmetry for commonly studied nerves are important in the clinical
      interpretation of nerve conduction data. We selected normal electrodiagnostic
      studies from archived electromyographic laboratory reports that included
      bilateral measurements of motor and sensory nerves. Symmetry of nerve conduction
      measures was confirmed, and only the median and ulnar sensory nerves had
      significant deviations from symmetry, supporting subclinical nerve damage in the
      most common dominant hand. The limits of symmetry were determined by calculating
      the 95th percentile for the differences between sides. For motor and sensory
      nerves, the range of 95th percentile limits was narrower for measures in upper
      extremity nerves compared to lower extremity nerves. Several reasons are offered
      for the wider limits of symmetry in lower extremity nerves.

PMID- 9533785
TI  - Protein phosphorylation in fast and slow chicken skeletal muscles: effect of
      denervation.
AB  - We have identified proteins in adult chicken skeletal muscle whose
      phosphorylation can be used as markers for the mature fast and slow muscle
      phenotype. These include phosphorylase, phosphorylase kinase, and a cyclic
      adenosine 3',5'-monophosphate (cAMP)-stimulated, calmodulin-inhibited 28-kDa band
      (markers for fast muscle), a calmodulin-stimulated 50-kDa band, and two cAMP
      stimulated bands at 44 and 46 kDa (markers for slow muscle), and the relative
      concentrations of the regulatory subunits of cAMP-dependent protein kinase (RI
      and RII). After denervation the pattern of phosphorylation in fast muscle changed
      to resemble that of slow muscle: phosphorylation of the fast phenotype markers
      decreased; the slow phenotype markers, barely detectable in normal fast muscle,
      appeared as significant phosphoproteins; and the concentration of RII increased
      with no change in RI. This is consistent with denervation-induced changes
      observed using other phenotypic markers and indicates the potential for using
      these phosphoprotein markers in studies of muscle development and
      pathophysiology.

PMID- 9533786
TI  - Innervation of the human anterior urethra by the dorsal nerve of the penis.
AB  - Previous neuroanatomic studies have demonstrated that branches of the dorsal
      nerve of the penis (DNP) innervate the anterior urethra. This study utilized
      electrodiagnostic techniques to confirm this finding. Electrical stimulation of
      the urethra resulted in responses recorded in the main trunk of the DNP, and
      responses were recorded from the urethra following stimulation of the DNP. A
      bulbocavernosus reflex was evoked after urethral stimulation. Urethral afferent
      impulses have a role in reflex ejaculatory function.

PMID- 9533787
TI  - AAEM case report 32: nerve injury associated with hip arthroplasty.
AB  - Hip Arthroplasty to alleviate pain related to arthritic degeneration has become
      one of the most common orthopedic procedures performed. As the elderly population
      expands, the number of such procedures can be expected to continue to increase.
      An electrodiagnostic evaluation can aid in localization, help identify the
      mechanism of injury, and be used as a tool to identify the nature and severity of
      the nerve pathology. Electrodiagnosis can also be used to generate a prognosis
      for recovery from nerve damage following hip surgery.

PMID- 9533788
TI  - Sciatic schwannoma of the thigh causing foot pain mimicking plantar neuropathy.
AB  - Two patients with plantar foot pain, one mistakenly thought to have tarsal tunnel
      syndrome, had complete resolution of pain after resection of a sciatic nerve
      schwannoma of the midthigh. The entire extent of the sciatic nerve should be
      evaluated in patients presenting with unilateral, neuropathic foot pain.

PMID- 9533789
TI  - Transcutaneous access to retrograde axonal flow.
AB  - Transcutaneous entry of fluorescent tracer and subsequent retrograde neuronal
      transport achieved by the use of dimethyl sulfoxide (DMSO) as a vehicle
      fluorescent dye dissolved in DMSO and applied topically to the hind limb of rats
      was found in corresponding dorsal root ganglia; aqueous absorption of tracer dye
      by neuronal tissue was not demonstrated. This example of transcutaneous access
      and retrograde transport may have implications as to the entry of various toxins,
      viruses, chemicals, and therapeutic agents to the nervous system.

PMID- 9533790
TI  - Fasciculation potentials in healthy people.
AB  - The aim of this study was to investigate the fasciculation potentials (FPs) in
      the small-peripheral muscles of the foot and hand and the possible associated
      factors, in a healthy population. One hundred-twenty-two normal individuals (65
      men and 57 women), aged 17-67 years (mean 39.96, SD=12.76) participated in the
      study. A special questionnaire consisting of 47 questions was devised as the
      basic instrument of the interview, which included the Hamilton anxiety rating
      scale. The extensor digitorum brevis (EDB), the flexor hallucis brevis (FHB) and
      the first dorsal interosseous (FDI) muscles were studied bilaterally using
      surface electrodes. In 94 (58 men and 36 women) from 122 participants (65 men and
      57 women) FPs were recorded (men 89.2%, women 63.1%, all 77%). The mean FPs per
      minute and muscle, in all three muscles, was 8.0 (SD=4.6). More FPs were recorded
      in the muscles of foot than in FDI (p<0.01) and in FHB than in EDB (p<0.001). FPs
      were correlated to gender, body height and weight and to the score of the
      Hamilton scale (r2>0.1, p<0.01). The syndrome of benign FPs was observed in 2 men
      (1.6% of men). These results suggest that FPs are a very common phenomenon in the
      peripheral muscles of healthy persons.

PMID- 9533791
TI  - Force and stiffness of old dystrophic (mdx) mouse skeletal muscles.
AB  - It has recently been suggested, based on studies of tissue pathology, that the
      limb muscles of old mdx mice may be a good model for the muscular changes seen in
      human Duchenne muscular dystrophy. To test this hypothesis, we measured force and
      stiffness of soleus and extensor digitorum longus (EDL) muscles of old (20-21
      months) mdx mice and age-matched controls. The mdx and control muscles generated
      similar twitch, tetanic, and eccentric forces. They were also equally stiff. The
      results show that the mechanics of aged mdx limb muscles differ greatly from
      Duchenne muscular dystrophy in humans, and disagree with the hypothesis.

PMID- 9533792
TI  - Computed tomographic study of the skeletal musculature of the lower body in 45
      postpolio patients.
AB  - Muscle computed tomography (CT) and muscle strength assessment of the pelvic
      girdle and leg muscles were performed in 32 postpolio patients experiencing new
      muscle weakness, and in 13 postpolio patients with stable neuromuscular
      condition. Muscles of the postpolio patients experiencing new muscle weakness
      showed significantly more CT scan abnormalities as compared with the stable
      postpolio patients. No other features discriminative of symptomatic postpolio
      patients were found. In individual patients, muscle CT scan evaluation is a
      useful adjunct to muscle strength assessment.

PMID- 9533793
TI  - Sarcolemmal excitability in myotonic dystrophy: assessment through surface EMG.
AB  - A motor point stimulation protocol was carried out on the tibialis anterior of
      myotonic dystrophy (MyD) patients. The surface myoelectric signal was monitored
      to record average rectified value (ARV), median frequency of power spectrum
      (MDF), and conduction velocity (CV) parameters. The ARV curve showed a decreasing
      trend that reveals a reduction in the M-wave amplitude during stimulation. MDF
      presented a significant decrement in the first seconds of sustained contraction,
      probably caused by abnormal lengthening of the depolarization zone. CV was
      significantly lower in patients, suggesting reduced mean fiber size.

PMID- 9533794
TI  - Muscle fiber type-specific myofibrillar actomyosin Ca2+ ATPase activity in
      multiple sclerosis.
AB  - Biopsies of tibialis anterior muscle were analyzed to determine if increased
      energy demand of contraction, as indirectly reflected by myofibrillar actomyosin
      Ca2+ ATPase (qATPase) activity, contributes to symptomatic fatigue in multiple
      sclerosis (MS). qATPase activity showed a fiber-type effect, IIax > IIa > I.
      Fiber-type qATPase activity, however, was not different between MS patients and
      healthy controls. We suggest that fatigue in MS does not reflect increased energy
      demand of contraction.

PMID- 9533795
TI  - Colchicine-induced myopathy with myotonia.

PMID- 9533796
TI  - Familial autosomal-dominant carpal tunnel syndrome presenting in a 5-year-old
      case.

PMID- 9533797
TI  - Transcranial magnetic stimulation (TMS) induces inhibition at a cortical level.

PMID- 9533798
TI  - The value of laryngeal electromyography in vocal cord paralysis.

PMID- 9533799
TI  - The severely obese patient: neglected again?

PMID- 9533800
TI  - Laparoscopic herniorrhaphy: review of complications and recurrence.
AB  - Laparoscopic hernia repair has evolved considerably since its introduction.
      Different methods have been described, and multiple studies have been performed
      reporting widely varying outcomes. This study was undertaken to review all the
      major publications on laparoscopic herniorrhaphy from 1993 to 1996 and evaluate
      the rates of recurrence and complications involved in the various techniques. In
      a total of 11,222 laparoscopic hernia repairs, the procedure performed most
      frequently was the transabdominal preperitoneal patch (TAPP), followed by the
      total extraperitoneal patch (TEP). There were 300 (2.7%) recurrences. From 9,955
      hernia repairs, there were 1,534 (15.4%) complications. Hematoma/seroma (456),
      neuralgia (199), urinary retention (150), and chronic pain (39) were the most
      frequently reported complications. Laparoscopic herniorrhaphy is a higher
      effective method of hernia repair with results comparable with the open
      technique. TAPP is still the most widely performed technique. TEP is becoming
      more popular, mainly because of its excellent outcome. The major drawback of TEP
      is the difficulty of reproducibility by different general surgeons with
      comparable results. Other techniques such as plug and patch carry a high rate of
      recurrence and complications and should probably be completely abandoned.

PMID- 9533801
TI  - The mechanics underlying laparoscopic intra-abdominal surgery for obese patients.
AB  - Any surgeon experienced with a laparoscopic approach to intra-abdominal surgery
      on morbidly obese patients is aware of the increased difficulty associated with
      the patients' obesity. We present a study of the mechanics of laparoscopic
      surgery that explains the difficulty subjectively experienced in terms of the
      decreased sensitivity felt by the surgeon as a result of the increased thickness
      of the abdominal wall and increasing force required for the repositioning of the
      tip of the operating instrument. We propose that the placement and angling of the
      trocar in the abdominal wall are of paramount importance in the successful and
      safe completion of laparoscopic procedures in obese patients.

PMID- 9533802
TI  - A practical approach to laparoscopic surgery for malfunctioning peritoneal
      dialysis catheters.
AB  - Peritoneal dialysis is widely accepted for the chronic management of end-stage
      renal disease but is associated with as high as a 70% complication rate including
      a significant problem with peritoneal dialysis catheter flow obstruction. The
      application of laparoscopic surgical techniques has revolutionized the surgical
      approach to peritoneal dialysis catheter-related dysfunction. However, the
      specific laparoscopic surgical technique varied among the reported literature.
      This lack of a standard laparoscopic surgical approach to obstructed peritoneal
      dialysis catheters prompted us to review and compare our specific technique and
      experience in 17 patients with 10 recent reported series. We specifically
      examined for insufflation techniques, access port placements and closures, timing
      postoperatively for reinstituting peritoneal dialysis, wound complications, and
      overall long-term success rates for peritoneal dialysis catheter salvage.

PMID- 9533803
TI  - Initial experiences with the retroperitoneal approach for endoscopic nephrectomy
      with the patient in the prone position.
AB  - Retroperitoneal endoscopic nephrectomy with the patient in the prone position was
      performed in 12 patients. Indications for this procedure were end-stage kidneys
      with ureteropelvic junction stenosis or distal ureteric obstruction,
      nonfunctional kidneys with drug resistant renin-mediated hypertension, and distal
      ureter malignancy. The retroperitoneal area was exposed using an open surgical
      technique in combination with the use of a liquid-filled dissection balloon.
      Removal of kidney tissue was performed with a morcellator through one of the
      ports. On average, the operating time was 210 min (range 160-480 min) to complete
      a one-sided nephrectomy. No major complications occurred. Mean hospital stay in
      this series was 6.6 days, and the follow-up period was uncomplicated in all
      cases. Retroperitoneal endoscopic nephrectomy with the patient in the prone
      position is an acceptable alternative to open nephrectomy in selected
      indications.

PMID- 9533804
TI  - The incidence of secondary hernias diagnosed during laparoscopic total
      extraperitoneal inguinal herniorrhaphy.
AB  - During a 24-month period beginning in July of 1995, laparoscopic total
      extraperitoneal inguinal herniorrhaphy was attempted in 53 patients. All
      procedures were performed at a single institution, by senior-level general
      surgery residents, with the same attending surgeon functioning as first
      assistant. Three patients required conversion to an "open" procedure (all had a
      prior history of herniorrhaphy or lower abdominal surgery), leaving 50 patients
      for analysis. Preoperatively, a unilateral hernia was evident on clinical grounds
      in 29 patients, the remaining 21 presenting with signs of a bilateral hernia; of
      the total, 11 had a history of prior hernia repair on the presently affected
      side. At surgery, a total of 115 hernia defects (indirect, direct, femoral) were
      identified, 38% of which were discovered only at the time of surgery. Sixty-four
      percent of patients were found to have at least one of these "secondary" hernias.
      After reduction of the hernia(s), all defects were covered with polypropylene
      mesh secured with spiral tacks. There were 10 perioperative complications, one of
      which required corrective surgical intervention. Over 70% of patients were
      discharged on the day of surgery; 92% returned home within 23 h of their
      operation. The most common reason for delay of hospital discharge was urinary
      retention. There have been no recurrences in short-term follow-up. Most patients
      were pleased with the recovery time from and the cosmetic results of their
      surgery. These results suggest that laparoscopic total extraperitoneal
      herniorrhaphy represents a safe, effective, cosmetically appealing alternative to
      open hernia repair. Moreover, this approach may provide an added advantage
      insofar as identifying additional hernia defects that, when repaired, may
      ultimately yield a lower recurrence rate than might otherwise have been expected.

PMID- 9533805
TI  - Laparoscopy in the diagnosis and management of Crohn's disease.
AB  - We have tried to evaluate the role of laparoscopy and laparoscopic-assisted
      surgery in the management of Crohn's disease. Over a 4-year period, we had 38
      patients, of which 23 patients were suspected to have Crohn's disease and were
      admitted for diagnostic laparoscopy while 15 patients had already had a biopsy
      confirmation of Crohn's disease in the past and were admitted for specifically
      planned procedures. In the first group of 23 patients, 11 were found not to have
      Crohn's disease. In the remaining 12 patients, three were proven to have Crohn's
      disease, but no surgical procedure was undertaken. The remaining nine patients
      underwent laparoscopic-assisted procedures, of which two required conversion to a
      laparotomy because of intra-abdominal abscesses. All 15 patients in the second
      group underwent laparoscopic or laparoscopic-assisted procedures. In total, 14
      patients were spared a potential diagnostic laparotomy and could go home the next
      day. The remaining 24 patients underwent procedures requiring longer hospital
      stays; five had a purely laparoscopic procedure, 17 had a laparoscopic-assisted
      procedure, and two required a laparotomy. Although there was little difference in
      the median stay for patients treated laparoscopically or by laparotomy, it is
      thought that the extent or severity of the disease process influenced the length
      of the stay rather than the approach used. The complication rate was similar to
      that found in Crohn's patients undergoing open surgery. It remains to be seen
      whether those in the laparoscopically treated group have less adhesive
      complications than those treated by laparotomy. It is our belief that laparoscopy
      is a valuable aid in the diagnosis of Crohn's disease. It remains to be proven
      whether or not laparoscopic-assisted surgery will be of significant value in the
      treatment of this condition.

PMID- 9533806
TI  - High-level disinfection with 2% alkalinized glutaraldehyde solution for reuse of
      laparoscopic disposable plastic trocars.
AB  - The reusability of disposable plastic trocars after high-level disinfection by
      alkalinized 2% glutaraldehyde solution was examined in a prospective study from
      the point of view of infection risk in order to determine the safety and economic
      benefits. For this purpose, 45 laparoscopic cholecystectomy cases were analyzed
      microbiologically and clinically. In 30 cases, trocars subjected to 15 min of
      disinfection by glutaraldehyde were used. In the remaining 15 cases, new trocars
      were used and a control group was established. In total, eight culture samples
      were taken from trocars, laparoscope (as it is disinfected by the same method),
      glutaraldehyde solution and umbilicus of the patients preoperatively; and from
      the bile in the gallbladder, peritoneal lavage fluid, and epigastric and
      umbilical incisions postoperatively. Only one of the disinfected trocars yielded
      a culture-positive result. No culture-positive results were found in the samples
      taken from laparoscope, glutaraldehyde, and epigastric incisions. Culture
      positive results were obtained in 11 cases at the umbilicus, in one case at the
      peritoneal lavage and in one case at the umbilical incision. None of the patients
      had infection at the wound site or intra-abdominally. In conclusion, we have
      shown that disposable plastic trocars subjected to high-level disinfection can be
      reused safely without infection risk and that cost can be reduced.

PMID- 9533807
TI  - Laparoscopic gastric bypass for morbid obesity in a patient with situs inversus.
AB  - The purpose of this article is to discuss the operative challenges posed by the
      advanced laparoscopic approach to a patient with situs inversus. The patient is a
      morbidly obese woman who has multiple co-morbidities related to her weight and
      who presented for bariatric surgery. A laparoscopic gastric by-pass was
      successfully performed. Situs inversus totalis is not a contraindication for
      laparoscopic surgery.

PMID- 9533808
TI  - Laparoscopic intracavitary drainage of subphrenic abscess.
AB  - Percutaneous drainage is now the preferred initial treatment of subphrenic
      abscess. The result is best for simple, unilocular abscesses but less so for
      complex ones. Failure of drainage can lead to high morbidity and mortality. We
      describe a case in which a large multiloculated subphrenic abscess was
      successfully drained laparoscopically without contaminating the general
      peritoneal cavity.

PMID- 9533809
TI  - Regarding "Small bowel obstruction as a complication of laparoscopic
      extraperitoneal inguinal hernia repair".

PMID- 9533810
TI  - Effects of calcitonin gene-related peptide on somatostatin and gastrin gene
      expression in rat antrum.
AB  - The ability of exogenous calcitonin gene-related peptide (CGRP) to regulate
      gastric somatostatin and gastrin messenger RNA was studied in vitro in rat antral
      mucosal/submucosal tissues. Somatostatin and gastrin mRNA were quantified by
      Northern and dot blot hybridization and regulatory peptides were measured by
      radioimmunoassay. Incubation of antral tissues in the presence of CGRP [1 x 10(
      7) M] for 60 min resulted in a reciprocal increase in somatostatin and a decrease
      in gastrin release: 214.7+/-28.5 vs. control of 81.7+/-5.9 pg somatostatin per
      gram of tissue and 2.2+/-0.3 vs. control of 5.5+/-0.7 ng gastrin per gram of
      tissue (P < 0.001). CGRP caused parallel changes in somatostatin and gastrin mRNA
      levels: somatostatin mRNA increased by 212% from 0.40+/-0.02 to 1.25+/-0.09
      absorbance units (AU) (P < 0.001) and gastrin mRNA decreased by 73% from 0.55+/
      0.08 to 0.15+/-0.02 AU (P < 0.001). Somatostatin monoclonal antibody prevented
      CGRP-mediated inhibition of both gastrin release and gastrin mRNA levels. In
      conclusion, CGRP is capable of modulating both the secretion and gene expression
      of regulatory peptides from antral G and D cells. Somatostatin
      immunoneutralization studies suggest that the actions of CGRP on gastrin release
      and gene expression are indirect and mediated through the paracrine influences of
      somatostatin.

PMID- 9533811
TI  - Age-related differences in the thermogenic and ponderal effects following the
      administration of fragment peptides from the rat ob protein.
AB  - The ob gene encodes a protein, which regulates satiety, metabolic rate and fat
      storage. The administration of a pool of five 20-amino-acid fragment peptides
      derived from the carboxy-terminal region of the ob protein produced a
      statistically significant reduction in body weight gain in adult rats, while
      rectal temperature showed a statistically significant increase. Administration of
      the same pool of peptides to young rats did not produce changes in body weight
      gain, although a statistically significant transient increase in rectal
      temperature was observed. These results envisage the possibility that small
      sequences of amino acids derived from the ob protein may mimic the effects of the
      whole protein on temperature and ponderal regulation. Furthermore, data suggest
      possible age-related differences in the response to leptin administration.

PMID- 9533812
TI  - Cholecystokinin- and secretin-releasing peptides in the intestine--a new
      regulatory interendocrine mechanism in the gastrointestinal tract.
AB  - Maintenance of homeostasis in the upper small bowel is a vital process for the
      body and therefore highly controlled. The enteric nervous system and the
      endocrine system are the regulators in this process influencing each other. The
      endocrine system in the gut consists of the classical hormones [cholecystokinin
      (CCK) secretin] to evoke motility or secretion. They are under control of
      releasing factors which are probably influenced by the enteric nervous system.
      Diazepam binding inhibitor and luminal CCK-releasing factor are likely candidates
      for CCK-releasing peptides in the negative feedback process in the absence of
      pancreatic juice. Experimental evidence suggests a secretin-releasing peptide.
      Further studies will be needed to determine the physiological role of each of
      these peptides. Monitor peptide in the pancreatic juice seems to function as a
      specific positive enhancement for CCK release. All these peptides are inactivated
      by the proteolytic enzymes during the interdigestive period. The discovery of
      additional releasing peptides and factors is very likely.

PMID- 9533813
TI  - Lack of beneficial effect of a tachykinin receptor antagonist in experimental
      colitis.
AB  - Nerves within the wall of the intestine may contribute to inflammatory responses,
      such as those occurring in inflammatory bowel disease. Studies in an experimental
      model of colitis have demonstrated that neuromodulation, through chemical
      sympathectomy or administration of lidocaine, can markedly attenuate granulocyte
      infiltration and tissue injury. Given the many pro-inflammatory effects of
      substance P, we have evaluated the effects of a tachykinin receptor (NK-1)
      antagonist, RP 67580, in models of acute colitis in the rat and guinea pig. While
      administration of RP 67580 and a second NK-1 antagonist (CP-96,345-1)
      significantly reduced the infiltration of granulocytes into colonic tissue during
      the first 12 h after induction of colitis in the rat, repeated administration of
      RP 67580 over a three day period failed to significantly affect granulocyte
      recruitment or the severity of tissue injury. In contrast, lidocaine enemas were
      effective in reducing both indices of inflammation/injury. In the guinea pig,
      similar observations were made. These observations demonstrate that blockade of
      NK-1 receptors over a three day period failed to significantly modify the course
      of experimental colitis. It remains possible that the beneficial effects of
      lidocaine may be due, in part, to inhibition of substance P release, and that the
      contribution of substance P to inflammation in experimental colitis occurs
      through NK-1 receptor-independent mechanisms.

PMID- 9533814
TI  - Analysis of angiotensin type 2 receptors in vasopressinergic neurons and
      pituitary in the rat.
AB  - Previous functional studies indicated that an angiotensin type 2 (AT2) receptor
      subtype may participate in the regulation of vasopressin release by angiotensin
      II (AngII). In the present study, AT2 receptor-directed antiserum
      immunohistochemically detected AT2 receptors within the hypothalamic
      paraventricular (PVN) and the supraoptic nuclei (SON) of the rat brain, more
      specifically, in identified vasopressinergic neurons. Considering the lack of AT2
      binding in the PVN and the SON using receptor autoradiography, we tested the
      hypothesis that these AT2 receptors are transported to the posterior pituitary.
      Western blot analysis detected AT2 immunoreactivity in the posterior pituitary.
      However, no AT2 binding was detected in posterior pituitary membranes, and no AT2
      binding was detected with quantitative receptor autoradiography in the
      neurohypophysis. Thus, if AT2 receptors are transported from the magnocellular
      vasopressin neurons to the posterior pituitary, their role in AngII regulation of
      vasopressin release at the neurohypophyseal terminals remains to be clarified.

PMID- 9533815
TI  - Kinin receptors mediating the effect of bradykinin on gastric acid secretion.
AB  - Kinins, and bradykinin in particular, can affect electrolyte transport in
      different segments of the intestine, thus being able to stimulate chloride
      secretion. Since the stomach is the main chloride secretory unit in the
      gastrointestinal tract, we have investigated the effect of bradykinin on acid
      secretion in the isolated frog (Rana catesbeiana) gastric mucosa. Bradykinin [2 x
      10(-8) to 2 x 10(-6) M] and des-Arg9-bradykinin [2 x 10(-9) to 2 x 10(-7) M] were
      able to stimulate acid secretion in a dose-dependent manner. The bradykinin [2 x
      10(-7) M] and des-Arg9-bradykinin (2 x 10(-8) M]-induced acid secretion was
      unaffected by Thi5,8,D-Phe7-bradykinin [2 x 10(-7) to 2 x 10(-5) M], a B2-kinin
      receptor antagonist. Interestingly, the B1-kinin receptor antagonist, des-Arg9
      (Leu8)-bradykinin [2 x 10(-7) to 2 x 10(-5) M] blocked both bradykinin- and des
      Arg9-bradykinin-stimulated acid secretion. Although the kininase I inhibitor, D-L
      mercapto-methyl-3-guanidino-ethyl-propanoic acid [2 x 10(-6) and 2 x 10(-5) M]
      had no effect on des-Arg9-bradykinin-induced acid secretion, it inhibited the
      response to bradykinin. We conclude that bradykinin requires, at least in part,
      hydrolysis to des-Arg9-bradykinin to increase gastric acid secretion and that its
      effect is mediated by B1-kinin receptors.

PMID- 9533816
TI  - Involvement of tetrodoxin-sensitive sodium channels in rat growth hormone
      secretion induced by pituitary adenylate cyclase-activating polypeptide (PACAP).
AB  - Both pituitary adenylate cyclase-activating polypeptide-38 (PACAP-38) and growth
      hormone-releasing hormone (GRH) stimulated growth hormone (GH) release from
      perfused rat anterior pituitary cells. Tetrodotoxin (TTX) blunted the GH release
      induced by PACAP-38 but not by GRH. Mefenamic acid, a blocker of non-selective
      cation channels, unaffected GH release elicited by PACAP-38 and GRH. These
      results suggest an involvement of TTX-sensitive Na+ channels but not Ca2+
      activated nonselective cation channels in PACAP-38-induced GH secretion, and that
      post-receptor mechanisms for PACAP-38 are different from those activated by GRH.

PMID- 9533817
TI  - Neuropeptide Y gene expression in immortalized rat hippocampal and
      pheochromocytoma-12 cell lines.
AB  - Employing clonal cell lines derived from rat embryonic hippocampal cells, we
      detected neuropeptide Y (NPY) mRNA in three progenitor subcloned cell lines.
      These cell lines upon differentiation express markers indicative of commitment to
      either neuronal (H19-7; NF +, GFAP -), glial (H19-5; GFAP +, NF -), or
      bipotential (H583-5; NF +, GFAP + ) lineages. Induction of differentiation was
      associated with the persistence of the NPY mRNA, however, in the differentiated
      H19-7 cells a 20-fold increase in NPY mRNA levels was observed (P<0.05). NPY
      immunoreactivity was observed only in cells with a differentiated neuronal
      phenotype. The cellular radioimmunoassayable NPY peptide levels increased twelve
      fold without a change in extracellular NPY peptide levels by multi-factorially
      induced neuronal or glial cell differentiation. The differentiated H19-5 cells
      expressed lower levels of NPY that could not be immunocytochemically detected.
      The peripheral sympathetic PC-12 neuronal cells examined in the undifferentiated
      and nerve growth factor-driven differentiated states expressed NPY only upon
      differentiation. We conclude that NPY is expressed by the cultured
      undifferentiated and differentiated rat hippocampal clonal cell lines, while the
      peripheral sympathetic PC-12 neuronal cell line only expresses the NPY gene upon
      differentiation. These immortalized embryonic neural cell line(s) will provide a
      hippocampal cell line(s) to conduct future in-vitro investigations targeted at
      determining the cellular and molecular mechanisms governing NPY gene expression.

PMID- 9533818
TI  - Blockade of the classical pathway of protein secretion does not affect the
      cellular exportation of lipocortin 1.
AB  - The mechanism by which lipocortin 1 (LC1) is extruded from cells in the brain and
      periphery in response to a glucocorticoid challenge is unknown. This study
      examined the influence of three inhibitors of the classical endoplasmic reticulum
      Golgi pathway of protein secretion on the dexamethasone-induced (0.1 microM, 2-3
      h) cellular exportation of LC1 in vitro in brain (cortex, hippocampus,
      hypothalamus), anterior pituitary tissue and peritoneal macrophages. In all
      instances, the steroid-induced exportation of LC1 was unaffected by brefeldin A
      (1.4 microM), monensin (10 microM) and nocodazole (3.3 microM); however, these
      drugs readily blocked the release of corticotrophin from pituitary tissue. These
      data suggest that LC1 is exported by a mechanism distinct from the classical
      pathway of protein secretion.

PMID- 9533819
TI  - New aspects of gastric adaptive relaxation, reflex after food intake for more
      food: involvement of capsaicin-sensitive sensory nerves and nitric oxide.
AB  - To accommodate the intake of food or liquid, gastric reservoir functions are
      important as the physiological reflex. There exist two major responses as a
      reservoir function of the stomach; adaptive and receptive relaxations. Adaptive
      relaxation is a reflex in which the fundus of the stomach dilates in response to
      small increases in intragastric pressure when food enters the stomach. Receptive
      relaxation is a reflex in which the gastric fundus dilates when food passes down
      the pharynx and the esophagus. The mechanisms of these two types of functional
      responses are to some extent different, although a nitric oxide (NO) dependent
      non adrenergic, non cholinergic neural pathway is involved in the both relaxation
      reflexes. Adaptive relaxation is an intragastric pressure induced reflex. Stretch
      of the gastric wall activates the mechanoreceptors in gastric mucosa (Mu), which
      generate impulses carried by the capsaicin-sensitive afferent sensory neuron. The
      sensory neuron can synapse on the inhibitory efferent neuron directly or activate
      it via interneurons of the myenteric plexus. This leads to the release of NO from
      the nitroxergic efferent neuron, which causes relaxation of circular muscle and
      hence of the fundus. Alternatively, an axon reflex causes the NO release from the
      sensory neuron, resulting in hexamethonium resistant gastric relaxation.
      Receptive relaxation is mediated by vagal motor fibers. In contrast with the
      pressure-induced adaptive relaxation, ganglionic nicotinic transmission is
      essential in the vagally induced relaxation. VIP and CGRP are important
      neurotransmitters of the inhibitory sensory neuron, which, however, may not
      mediate both adaptive and receptive relaxations. Disorders of these reservoir
      functions result in symptoms of early satiety and anorexia, which are the major
      symptoms of patients with functional dyspepsia.

PMID- 9533820
TI  - The effect of extracellular Ca2+ on responses to purinoceptor agonists in
      cultured swine tracheal smooth muscle cells.
AB  - The effects of extracellular Ca2+ ions on purinergic responses were examined in
      swine tracheal smooth muscle cells (TSMCs) in primary culture. ATP (1 microM to 1
      mM) and alpha, beta-methylene adenosine 5' triphosphate (alpha, beta-Me ATP) (100
      microM and 1 mM) concentration-dependently increased [Ca2+]i in the presence and
      the absence of extracellular Ca2+. Responses to ATP (10 microM to 1 mM) in the
      presence of extracellular Ca2+ were significantly larger than those in its
      absence (n=8), whereas those to alpha, beta-Me ATP were not significantly
      different between the presence (n=7) and the absence (n=8) of extracellular Ca2+.
      Responses to ATP (1 mM) at extracellular Ca2+ concentration ([Ca2+]o) of 10 and 5
      mM were significantly larger than that at extracellular EGTA concentration
      ([EGTA]o) of 1 mM (p< 0.01, n=5), whereas the responses to alpha, beta-Me ATP (1
      mM) at 10 and 5 mM [Ca2+]o were significantly smaller than that at [EGTA]o of 1
      mM (p<0.05, n=5). Increasing [Ca2+]o to 5 mM after the application of either 1 mM
      ATP (n=4) or 1 mM alpha, beta-Me ATP (n=4) in the absence of extracellular Ca2+
      (1 mM [EGTA]o) further increased [Ca2+]i, though the increases in [Ca2+]i by
      agonists in 1 mM [EGTA]o had been already maximal. Incubating cells for 300 s in
      5 mM [Ca2+]o before the application of ATP (1 mM) significantly increased the
      response to the drug than that obtained by incubating cells for 6 sec in 5 mM
      [Ca2+]o before the drug application (p< 0.01, n=4). However, alpha, beta-Me ATP
      (1 mM) induced similar responses by incubating cells for 30 or 300 s in 5 mM
      [Ca2+]o to that by incubating them for 6 s. These results suggest that the effect
      of alpha, beta-Me ATP in swine TSMCs in primary culture is mainly through Ca2+
      release and that its effect on Ca2+ entry is smaller than other nucleotides.

PMID- 9533821
TI  - The beta2- and beta3-adrenoceptor-mediated relaxation induced by isoprenaline and
      salbutamol in guinea pig taenia caecum.
AB  - To understand the receptor subtypes responsible for beta-adrenoceptor-mediated
      relaxation of guinea pig taenia caecum, we investigated the effects of
      isoprenaline and salbutamol. Isoprenaline and salbutamol caused dose-dependent
      relaxation of the guinea pig taenia caecum. Propranolol, bupranolol and
      butoxamine produced shifts of the concentration response curves for isoprenaline
      and salbutamol. Schild regression analyses carried out for propranolol against
      isoprenaline and salbutamol gave pA2 values of 8.43 and 8.88, respectively.
      Schild regression analyses carried out for butoxamine against isoprenaline and
      salbutamol gave pA2 values of 6.46 and 6.68, respectively. Schild regression
      analyses carried out for bupranolol against isoprenaline and salbutamol gave pA2
      values of 8.60 and 8.69, respectively. However, in the presence of 3 x 10(-4) M
      atenolol, 10(-4) M butoxamine and 10(-6) M phentolamine to block the beta1-,
      beta2- and alpha-adrenoceptor effects, respectively, Schild regression analyses
      carried out for bupranolol against isoprenaline and salbutamol gave pA2 values of
      5.77 and 5.97, respectively. These results suggest that the relaxant responses to
      isoprenaline and salbutamol in the guinea pig taenia caecum are mediated by both
      the beta2- and the beta3-adrenoceptors.

PMID- 9533822
TI  - Further studies concerning possible transmitters from NANC nerves in the circular
      muscle of the rat stomach fundus.
AB  - We examined the characteristics of the non-adrenergic, non-cholinergic (NANC)
      inhibitory response of the circular muscle of the rat stomach fundus to
      transmural nerve stimulation or high K+. Treatments with isotonic high K+ (20
      mM), nitric oxide (NO) and sodium nitroprusside (SNP) all elevated cyclic GMP
      levels in the rat stomach fundus in the presence of atropine and guanethidine.
      Isotonic high K+-induced formation of cyclic GMP was completely inhibited by
      tetrodotoxin (TTX) or NG-nitro-L-arginine (L NNA). The K+ also increased cyclic
      AMP levels and this response was completely inhibited by TTX. Dose-dependent
      relaxation of the fundus in response to SNP was shifted to the right by a prior
      incubation with high concentration of SNP (10(-4) M) for 2 hrs. Incubating the
      fundus with SNP for 2 hrs significantly inhibited NO induced cyclic GMP
      formation. Relaxation responses to transmural stimulation (1 Hz or 30 Hz),
      isotonic high K+ and NO were significantly reduced by a prior incubation with
      SNP. Isotonic high K+ (20 mM)-induced relaxation of circular muscle strips was
      not completely inhibited by combined treatment with 10(-5)M L-NNA, 5 x 10(-5)M
      oxyhemoglobin and anti VIP (1:200). These results suggest that NO as well as VIP
      is possible transmitter from NANC nerves in the circular muscle of the rat
      stomach fundus and there should be one or more inhibitory mediators other than
      VIP and NO.

PMID- 9533823
TI  - Different types of vasocontractile responses to noradrenaline in the presence of
      platelets with platelet activating factor.
AB  - Platelet activating factor (PAF) is known to produce a wide variety of
      hemodynamic effects. The present study was carried out with the aim of
      elucidating the mechanism of PAF action on vasoconstrictive response to
      noradrenaline (NA-R) in the presence of autologous platelets. NA-R was examined
      in isolated perfused arterial segments. PAF action through stimulation of
      platelets by noradrenaline (NA) was explored during infusion of platelet rich
      plasma (PRP) with PAF into the perfusion circuit. Consequently, it was revealed
      that PRP with PAF elicited an initially augmented response, followed by gradually
      attenuated responses under conditions of low doses of NA (in the range of 5 to 25
      ng). However, the augmented responses were observed consistently under a higher
      dose of NA (50 ng). In addition, the gradually attenuated responses were reversed
      by adding tetrodotoxin, a Na-spike inhibitor. Thus, it is concluded that PAF
      action on NA-R through platelets may be related partly to neurotransmitters
      originating from perivascular autonomic depressant nerves stimulated by some
      neuroeffector agents.

PMID- 9533824
TI  - Source of ATP, ADP, AMP and adenosine released from isolated rat caudal artery
      exposed to noradrenaline.
AB  - Purines of ATP, ADP, AMP and adenosine released from rat caudal artery with and
      without endothelium and the isolated smooth muscle and endothelial cells were
      examined, in order to determine the source. Treatment of intact segments of
      caudal arteries with noradrenaline (10 microM) for 3 min induced a large release
      of ATP, ADP, AMP and adenosine. However, if the artery segments had been denuded
      of their endothelial lining, noradrenraline induced only a slight release of
      purines. Endothelial cells in primary culture prepared from caudal arteries, when
      exposed to noradrenaline for 3 min released large amounts of purines, whereas
      vascular smooth muscle cells prepared similarly and passaged endothelial cells
      did not release purines upon exposure to noradrenaline. These results indicate
      that, of smooth muscle and endothelial cells of the vascular wall, only intact
      endothelial cells react to alpha-adrenoceptor stimulation by releasing adenine
      nucleotides and adenosine.

PMID- 9533825
TI  - Nitric oxide relaxes bovine ciliary muscle contracted by carbachol through
      elevation of cyclic GMP.
AB  - It is generally accepted that nitric oxide relaxes vascular smooth muscles by
      activating guanylyl cyclase, which in turn increases cyclic 3':5' guanosine
      monophosphate level. Despite the physiological significance of nitric oxide, very
      few studies have attempted to characterize the mode of action of this mediator in
      ciliary muscles. Therefore, the present experiments were designed to investigate
      whether or not the relaxation induced by sodium nitroprusside as a donor of
      nitric oxide is accompanied by the increase in cyclic 3':5' guanosine
      monophosphate level in the bovine ciliary muscle, and these responses are
      affected by methylene blue as an inhibitor of guanylyl cyclase and 3-isobutyl-1
      methylxanthine as an inhibitor of phosphodiesterases. The relaxation activity of
      exogenous 8-bromo-cyclic 3':5' guanosine monophosphate was also determined.
      Sodium nitroprusside produced a concentration-dependent relaxation in the bovine
      ciliary muscle strips which had been contracted by carbachol as a cholinergic
      agonist. Relaxation in response to sodium nitroprusside was accompanied by a
      significant (P<0.05 and P<0.005) increase in cyclic 3':5' guanosine monophosphate
      level. The relaxation response and the increase in cyclic 3':5' guanosine
      monophosphate caused by sodium nitroprusside were significantly (P<0.01 and
      P<0.05) augmented by the pretreatment with 3-isobutyl-1-methylxanthine, and were
      significantly (P<0.005 and P<0.05) attenuated in the presence of methylene blue.
      The exogenously applied 8-bromo-cyclic 3':5' guanosine monophosphate relaxed the
      ciliary muscle strips in a concentration-dependent manner. These results suggest
      that nitric oxide causes relaxation of the bovine ciliary muscle through the
      activation of guanylyl cyclase and an increase in cyclic 3':5' guanosine
      monophosphate level.

PMID- 9533826
TI  - Regulation of endothelin-1 in human non-pigmented ciliary epithelial cells by
      tumor necrosis factor-alpha.
AB  - Endothelins (ET) are potent vasoactive peptides present in many ocular structures
      and are formed from precursor Big endothelins (Big ET-1) by the action of an
      endothelin-converting enzyme (ECE). ET-1 is thought to decrease intraocular
      pressure by contracting the ciliary muscle thus enhancing the outflow of aqueous
      humor through the Canal of Schlemm and trabecular meshwork. However, the
      mechanisms involved in the regulation of endothelin-1 (ET-1) synthesis and
      release in ocular tissues have not been fully characterized. In this study we
      examined the effect of tumor necrosis factor-alpha(TNF-alpha; 10 nm), a
      proinflammatory cytokine, on the cellular mechanisms leading to ET-1 synthesis
      and release in SV-40 transformed human ciliary non-pigmented epithelial cells
      (HNPE). ET-1 and Big endothelin-1 (Big ET-1) immunoreactivity was time
      dependently increased following TNF-alphatreatment. Phorbol esters (PMA),
      activators of PKC, also raised the immunoreactive levels of ET-1 and Big ET-1
      while, staurosporine, a PKC inhibitor (20 nm), decreased ET-1 levels in TNF-alpha
      stimulated cells. Pre-treatment with phosphoramidon (1 micron) an ECE-inhibitor,
      followed by TNF-alpha stimulation, decreased ir-ET-1 levels. Cycloheximide (9
      micron), a protein synthesis inhibitor, decreased TNF-alpha-stimulated levels for
      ir-ET-1 and ir-Big ET-1, suggesting that TNF-alpha may be directly regulating ET
      1 expression at the ET-1 gene. Our data indicates that TNF-alpha regulates ET-1
      levels in HNPE cells possibly by activating PKC either to stimulate protein
      synthesis and/or to enhance ET-1 secretion. These results suggest that ET-1
      released from the ciliary body may play an important role in aqueous humor
      dynamics following cytokine activation.

PMID- 9533827
TI  - Effects of perfluorooctylbromide and vitamin E on ischemia induced retinal
      oxidative tissue damage.
AB  - The aim of this study was to investigate the extent to which ischemia and
      reperfusion lead to oxidative damage of the retinal tissue and investigate how
      ischemic and reperfused retinal tissues react to the application of
      perfluorooctylbromide (PFOB) and, if this reaction can be influenced by
      protective drugs such as vitamin E (Vit.E). The experiments were performed with
      60 male Wistar rats, divided into 12 groups using an established model of
      reversible ischemia and reperfusion of the globe. Grouping of animals was carried
      out according to different ischemia and reperfusion periods and different
      therapeutic regimens (PFOB, Vit.E). Treatment with PFOB and/or Vit.E was
      performed after 60 min of ischemia with 60 min of reperfusion. At the end of the
      experiments thiobarbituric acid reactive substances (TBARS) were determined in
      the retinal tissues and served as parameters of oxidative tissue damage. Ischemia
      of up to 60 min led to a significant increase in TBARS values. Ninety and 120 min
      of ischemia led to no further significant elevation compared to the 60 min or 90
      min group. Following 60 min of ischemia, a reperfusion period of 15 min led to an
      increase in TBARS values that was significant (P<0.05) after 30 and 60 min.
      Addition of PFOB resulted in a further significant (P<0.05) increase in TBARS
      values as compared to the respective group without treatment. Vit. E alone did
      not change the values significantly compared to the respective group without
      treatment. However, the application of Vit.E in addition to PFOB led to a
      significant reduction in TBARS values. Ischemia resulted in severe oxidative
      retinal tissue damage, which increased during reperfusion. The reperfusion damage
      might be due to the known depletion of protecting substances such as vitamin E.
      Enhancement of oxygen supply by PFOB during reperfusion without any tissue
      protection leads to more severe damage. Thus, additional protection of the tissue
      by powerful antioxidants is necessary when providing oxygen for better tissue
      recovery.

PMID- 9533828
TI  - Investigation of dispersion effects in ocular media by multiple wavelength
      partial coherence interferometry.
AB  - We report on quantitative measurements of group refractive indices and group
      dispersion in water and in human ocular media such as the cornea, the aqueous
      humor, the lens, artificial intraocular lenses, as well as a total value averaged
      over the media along the axial eye length of normal subjects and pseudophakic
      patients in vivo using dual beam partial coherence interferometry. Different
      optical thickness values due to the dispersion of the cornea are demonstrated
      using two spectrally displaced light sources. The displacement can be used to
      indirectly calculate the group dispersion of the human cornea in the spectral
      region between 810 nm and 860 nm. If the object under investigation is
      dispersive, resolution is limited due to a broadening of the detected signals.
      This broadening increases with group dispersion, i.e., the extent to which the
      group refractive index of the medium varies with wavelength and thickness of the
      tissue under investigation as well as with the spectral bandwidth of the light
      source. Measurements of the group dispersion in the cornea, lens and vitreous of
      pseudophakic and normal human eyes, show that the cornea and the lens are more
      dispersive than water-by a factor of about 5 and 2, respectively-in the
      investigated spectral region. The cornea is approximately threefold more
      dispersive than the human crystalline lens, the aqueous humor is less dispersive
      than water and the group dispersion of all ocular components together, averaged
      over the axial length of normal and pseudophakic eyes, was only slightly higher
      compared to that of water. Since the highly dispersive cornea and lens together
      have only a thickness of about one sixth of that of the axial eye length, it
      seems that their contribution to the group dispersive effect along the whole
      axial eye length is only small.

PMID- 9533829
TI  - Activation of a Cl--conductance by protein kinase-dependent phosphorylation in
      cultured rat retinal pigment epithelial cells.
AB  - While chloride conductances are involved in signals of the electroretinogram
      generated by the retinal pigment epithelium (RPE), patch-clamp experiments of
      freshly isolated or cultured RPE cells have shown that potassium conductances
      predominate. The purpose of this study was to investigate mechanisms which
      activate Cl--conductances in RPE cells. Membrane currents of cultured rat RPE
      cells were measured using the whole-cell configuration of the patch-clamp
      technique under extra- and intracellular K+-free conditions. The bath solution
      was hyperosmolal to the pipette solution to prevent hypoosmotic swelling.
      Exchange of the physiological intracellular fluid by a pipette solution with
      physiological levels of ATP (2 mm) induced a continuous increase of membrane
      conductance. Conductance was blocked by DIDS (1 mm), and showed a reversal
      potential close to the Nernst potential for Cl-. When the experiments were
      carried out under conditions in which all cations, and not only potassium, were
      replaced by NMDG, the same responses could be observed. Current activation was
      independent of extracellular calcium. Chloride currents were also induced when
      ATPgammaS or AMP-PNP were used instead of ATP. In the presence of AMP-PNP
      currents were 10 times smaller than in the presence of ATP or ATPgammaS. In cells
      preincubated with staurosporine or chelerythrine no currents were induced.
      Establishing the whole-cell configuration with ATP and with myristoylated PKC
      substrate in addition, no voltage-dependent currents were activated. We conclude
      that ATP hydrolysis leads to activation of chloride currents via PKC in the whole
      cell configuration. The perforated patch configuration, with the intracellular
      compartment intact, no currents were induced under otherwise identical
      experimental conditions. Inhibition of phosphatase by calyculin (10 nm) in the
      perforated-patch configuration did not change membrane conductance. In the intact
      cell, chloride conductance is possibly inhibited by a cytosolic factor which is
      washed out when the whole-cell configuration is established.

PMID- 9533830
TI  - Effect of aclacinomycin A on in vitro cultures of porcine lens epithelial cells.
AB  - As a potential drug for the prevention of secondary cataract formation (SCF), we
      investigated the effect of Aclacinomycin A (ACM) on the growth of cultures of
      porcine lens epithelial cells in vitro. ACM is an anthracycline that has been
      used in the treatment of acute myeloid leukemia in the human for many years. It
      has been shown to be non-mutagenic and non-carcinogenic in in vitro and in animal
      models. Subconfluent cell cultures were exposed to different concentrations of
      ACM for 5 minutes. The drug effect was evaluated by cell counts after various
      lengths of culture time (between 1 and 10 weeks). No cells survived the treatment
      with 12 or 16 microg ml-1. Cultures treated with concentrations between 0.5 and 8
      microg ml-1 showed a marked decrease in cell number when compared to controls.
      However, reproliferation occurred at concentration up to 8 microg ml-1 after 2-6
      weeks. Intraocular application of ACM might be suitable in the prevention of SCF.
      However, with regard to reproliferation, long-term cultures (or long-term animal
      models, respectively) have to be used in further evaluating the appropriate
      dosage for this purpose.

PMID- 9533831
TI  - In vitro transplantation of fetal human retinal pigment epithelial cells onto
      human cadaver Bruch's membrane.
AB  - Retinal pigment epithelium transplantation has been proposed as adjunctive
      treatment for age-related macular degeneration following surgical excision of
      choroidal neovascular membranes. The goal of this study was to develop a model to
      evaluate retinal pigment epithelium transplantation onto human Bruch's membrane
      in vitro. We investigated the ability of cultured fetal human retinal pigment
      epithelium to colonize human cadaver Bruch's membrane, determined the incubation
      time needed to form a monolayer and to exhibit apical microvilli and tight
      junctions, and assessed the production of basement membrane. Freshly enucleated
      (less than 48 hours old) human eyes were cut through the pars plana, and the
      anterior segment, vitreous, and retina were removed. The native retinal pigment
      epithelium was debrided with a surgical sponge. Bruch's membrane and choroid at
      the macula were trephined with a 7.0 mm diameter trephine and then incubated with
      1/2 ml of Dulbecco's modified Eagle's medium +15% fetal calf serum+basic
      fibroblast growth factor (1 ng ml-1), and fetal human retinal pigment epithelium
      at a concentration of 242,000 cells ml-1. Specimens were incubated for 1, 4, 6,
      8, 12, or 24 hours. The specimens were fixed in half strength Karnovsky's
      fixative, processed, and analysed with scanning and transmission electron
      microscopy. The retinal pigment epithelium covered the debrided macular specimens
      to different degrees at different incubation times. After 1 hour, the cells
      started to attach and flatten (median percent coverage: 78%). The extent of
      Bruch's membrane coverage by fetal retinal pigment epithelium varied greatly
      between specimens. After 4-6 hours, the cells covered the entire debrided surface
      in a monolayer (median percent coverage: 97.2% at 4 hours, 99.8% at 6 hours).
      Tight junctions were observed, and the cells had few apical microvilli. The
      lateral cell borders were obliquely oriented with respect to Bruch's membrane,
      and the nuclei were elongated, exhibited prominent nucleoli, and were oriented
      parallel to Bruch's membrane. After 6-8 hours, cells started to become hexagonal
      (median percent coverage at 8 hours: 99.97%). Cells attached to the inner
      collagenous layer tended to be flatter than cells attached to residual native
      basement membrane. At 12 and 24 hours, expression of hexagonal shape, tight
      junctions, and apical microvilli were observed more frequently (median percent
      coverage: 99.87% at 12 and 100% at 24 hours). No newly formed basement membrane
      was observed at these time points. In separate experiments comparing attachment
      in the presence and absence of native RPE basement membrane, the presence of
      native retinal pigment epithelial basement membrane promoted the early attachment
      of the cells and more rapid expression of normal morphology. This in vitro system
      provides a reproducible way to study the adherence of retinal pigment epithelium
      to normal and diseased human Bruch's membrane.

PMID- 9533832
TI  - Identification of endothelin receptor subtypes in rat ciliary body using subtype
      selective ligands.
AB  - The endothelins are important vasoactive ocular peptides and there is some
      evidence that they may modulate intraocular pressure. We investigated the
      existence and localization of endothelin receptor subtypes using subtype
      selective ligands in rat ciliary body. Scatchard transformation of saturation
      binding experiments revealed that the KD and Bmax for [125I]ET-1 and [125I]ET-3
      to membranes from ciliary body were 41.7+/-9 pM and 236+/-20 fmol mg-1 protein
      and 37. 8+/-0.4 pM and 160+/-2.0 fmol mg-1 protein, respectively. Competitive
      experiments in the presence of cyclic pentapeptide BQ123 (selective for ETA
      receptors) and BQ3020 (selective for ETB receptors), demonstrated the existence
      of ETA and ETB receptors in a ratio of 35:65. Cross-linking of [125I]ET-1 and
      [125I]ET-3 to ciliary body membranes resulted in the labeling of two bands with
      apparent molecular masses of 52 and 34 kDa, suggesting that ETA and ETB receptors
      have similar molecular mass. The 34 Kda band is a proteolytic degradation product
      of the 52 Kda band. Autoradiographic results show that specific [125I]ET-1
      binding sites, displaced by BQ123 and BQ3020, are localized to the ciliary
      epithelium, supporting the idea that ETA and ETB subtype receptors exist in this
      tissue.

PMID- 9533833
TI  - Morphological and morphometric analysis on the rabbit conjunctival goblet cells
      in different hormonal conditions.
AB  - An altered conjunctival mucous secretion was reported in pregnancy or oral
      contraceptive use. Four groups of rabbits (males, dioestrous females, oestrous
      females, pregnant) were studied to determine whether sex and/or different
      physiological conditions could influence conjunctival goblet cells structure and
      ultrastructure. Light microscopy, transmission electron microscopy, and
      morphometry were performed. In males and in oestrous females the intracytoplasmic
      secretory granules were filled with granular material, whilst in pregnant and
      dioestrous females the granules were formed by a more homogenous and dense
      secretory material. The number of goblet cells was not statistically different in
      the groups studied, whilst pregnant animals showed the largest mean diameter. As
      to the secretory granules, their mean area was larger in dioestrous females,
      whilst their optical density was highest in pregnant animals. These observations
      indicate that the morphology of conjunctival goblet cell may vary according to
      sex and to different physiological conditions: this may account for the peculiar
      mucous secretion demonstrated during pregnancy.

PMID- 9533835
TI  - Induction of cross-links in corneal tissue.
AB  - The aim of this study was to investigate the possibility of induction of cross
      links in corneal tissue in order to increase the stiffness as a basis for a
      future conservative treatment of keratectasia. Collagenous biomaterials can be
      stabilized by chemical and physical agents. The epithelium of enucleated porcine
      eyes was removed. Eight test groups, 10 eyes each, were treated with UV-light
      (lambda=254 nm), 0.5% riboflavin, 0.5% riboflavin and UV-light (365 nm) blue
      light (436 nm) and sunlight, and the chemical agents-glutaraldehyde (1% and 0.1%,
      10 min) and Karnovsky's solution (0.1%, 10 min). Strips of 5 mm in width and 9 mm
      in length were cut from each cornea and the stress-strain behaviour of the strips
      was measured to assess the cross-linking process. For comparison, ten untreated
      corneas were measured by the same method. Compared to untreated corneas treatment
      with riboflavin and UV-irradiation as well as weak glutaraldehyde or Karnovsky's
      solutions resulted in an increased stiffness of the cornea. The biomechanical
      behaviour of the cornea can be altered by glutaraldehyde, Karnovsky's solution,
      and with riboflavin and UV-irradiation which offers the potential of a
      conservative treatment of keratoconus. To optimize this effect further
      investigation is necessary regarding the dose-response and in-vivo application.

PMID- 9533834
TI  - Ocular hypotension induced by intravitreally injected C-type natriuretic peptide.
AB  - The purpose of the study is to determine if intravitreal injection of c-type
      natriuretic peptide (CNP) affects intraocular pressure (IOP), aqueous humor
      dynamics and guanosine 3',5'-cyclic monophosphate (cGMP) concentration in the
      aqueous humor of the rabbit eye. Also we investigated whether CNP-like
      immunoreactivities (CNP-LI) were present in porcine aqueous humor and whether CNP
      LI were detected in rabbit and porcine ciliary body. The IOP was measured after
      intravitreal injection of 2 pmol approximately 20 nmol CNP into rabbit eyes.
      Aqueous humor dynamics (aqueous humor flow, outflow facility, and uveoscleral
      outflow) and cGMP concentration in the aqueous humor were determined at
      approximately 6 hr after CNP injection. The CNP concentration in aqueous was
      measured by radioimmunoassay in porcine eye, and CNP-LI were detected with a
      monoclonal antibody in porcine and rabbit eyes. Intravitreally injected CNP
      caused IOP reduction in a dose-dependent manner (P<0.0001) and the maximum effect
      was observed at 4 approximately 6 hr. CNP increased total outflow facility by
      approximately 35%, but did not affect aqueous humor flow or uveoscleral outflow.
      The cGMP concentration in the aqueous of CNP-treated eyes was about 4- to 14-fold
      higher than that in the contralateral untreated eyes. CNP concentration in
      aqueous was about 2-fold higher than that in plasma, and CNP-LI were found in non
      pigmented epithelium of the ciliary body of both rabbit and porcine eyes. CNP may
      play an important role in the regulation of IOP.

PMID- 9533836
TI  - Effects of hepatocyte growth factor, transforming growth factor-beta1 and
      epidermal growth factor on bovine corneal epithelial cells under epithelial
      keratocyte interaction in reconstruction culture.
AB  - In the cornea, corneal epithelial cells are in close contact with keratocytes:
      the epithelial cells organize thickened lamellar structure on a layer of
      keratocytes embedded in extracellular matrix (ECM). Thus, growth factors are
      expected to critically regulate corneal component cells under epithelial
      keratocyte interaction. The purpose of this study is to clarify effects of
      hepatocyte growth factor (HGF), transforming growth factor-beta1 (TGF-beta1) or
      epidermal growth factor (EGF) on corneal epithelial cells under epithelial
      keratocyte interaction. We examined proliferation and differentiation of the
      epithelial cells in a simple corneal reconstruction culture composed of an
      epithelial cell layer on the keratocyte-containing stromal layer, using three
      dimensional collagen gel matrix culture. We observed the morphological change by
      phase contrast microscopy, and conducted histological and immunohistochemical
      examinations. The epithelial proliferation was examined by nuclear bromodeoxy
      uridine (BrdU) uptake. In the reconstructed cornea under epithelial-keratocyte
      interaction, EGF-, TGF-beta1- and HGF-treated cells formed a thickened epithelial
      layer consisting of 5-6, 5-6 and 3-4 cells, respectively. In fact, both EGF and
      TGF-beta1 induced significantly higher intakes of nuclear BrdU of the epithelial
      cells than HGF. In lamellar differentiation of the epithelial cells, TGF-beta1-
      or HGF-treated cells formed a triple lamellar structure specific for the in vivo
      corneal epithelium: basal, middle and superficial layers are composed of cuboidal
      basal-like cells, spindle wing-like cells and flat superficial-like cells,
      respectively. TGF-beta1-treated cells formed a more markedly thickened epithelial
      layer than HGF-treated cells. In contrast, EGF formed a single lamellar structure
      consisting of cuboidal cells. These results suggest that those growth factors
      regulate proliferation and/or lamellar differentiation of corneal epithelial
      cells under epithelial-keratocyte interaction. The most interesting result was
      that TGF-beta1 promotes proliferation and lamellar differentiation of corneal
      epithelial cells through keratocyte-mediated stimulation.

PMID- 9533837
TI  - Long term follow-up of lenticular autofluorescence and transmittance in healthy
      volunteers.
AB  - This study was undertaken to assess long term changes in the lenticular
      autofluorescence and transmittance of healthy volunteers. Both eyes of 15 healthy
      volunteers aged 8 to 62 years were examined by slit-lamp examination and
      fluorophotometric measurements of lenticular autofluorescence (lambdaexc=415 nm
      490 nm, lambdaem= 510 nm-550 nm) and transmittance (lambda=415 nm-550 nm) in 1983
      and 1996. The changes in lenticular autofluorescence and transmittance between
      1983 and 1996 were determined and compared with those calculated on the basis of
      age-dependence curves of a group of 56 healthy volunteers measured in 1983. These
      curves were obtained by approximation of the values of the 56 healthy volunteers
      by a linear, polynomial or exponential function of age, respectively. A mean
      yearly increase of lenticular autofluorescence of 8.69 ng . equivalent
      fluorescein . ml-1 . year-1 was observed in the 15 volunteers between 1983 and
      1996 and this increase was significantly larger than that calculated on the basis
      of the three age-dependence curves in 1983 (6.36, 6.47 and 6.53 ng . equivalent
      fluorescein . ml-1 . year-1, P=0.0026, 0.0037 and 0.0044, respectively). The
      transmittance showed a mean yearly decrease of 0.508% . year-1 which was
      significantly larger than calculated on the basis of the three age-dependence
      curves in 1983 (0.153, 0.220 and 0.183% . year-1, P=0. 0033, 0.012 and 0.0059,
      respectively). One volunteer, i.e. the individual with the highest lenticular
      autofluorescence and lowest transmittance in 1983, had developed cataract in
      1996. These measurements demonstrate for the first time, quantitative changes in
      lenticular autofluorescence and transmittance in a long term follow up. The at
      least 35% larger increase of autofluorescence and 130% larger decrease in
      transmittance in the follow-up group between 1983 and 1996 in comparison with the
      values based on age-dependent curves in 1983 could be caused by the increased
      solar UV radiation in The Netherlands during that period of time.

PMID- 9533838
TI  - Announcements 

PMID- 9533839
TI  - Chemotactic activity of tears and bacteria isolated during adverse responses.
AB  - Inflammatory processes are characterized by the dynamic influx of leukocytes.
      This leukocyte recruitment and activation is thought to be initiated by chemical
      signals including chemotactic factors. This study was designed to investigate the
      chemotactic activity in different tear types and bacteria isolated during adverse
      responses to contact lens wear. Chemotactic activity was determined by
      quantitating in vitro neutrophil migration using a microchemotaxis chamber.
      Results demonstrated that tears collected immediately after 8 hours sleep
      (P<0.001) and tears collected during adverse responses (P<0.001) showed
      significantly higher chemotactic activity compared to reflex tears. Specific
      neutralizing antibodies to IL-8, LTB4 and C5a were added to closed eye and
      adverse response tears. Pre-incubation of closed eye tears with antibodies to IL
      8 showed a significant reduction in chemotactic activity (P<0.0001), whereas a
      significant reduction of PMN migration in adverse response tears was observed
      after pre-treatment with antibodies to LTB4 (P<0.0001). However no difference in
      chemotactic activity was observed after incubation with antibody to C5a or
      irrelevant antibody. Dot blots demonstrated that closed eye tears contained
      approximately 150 ng ml-1 IL-8 and adverse response tears contained 2 ng ml-1 IL
      8. Most Gram negative bacteria isolated from contact lenses caused directed
      migration of PMNs. Addition of neutralizing antibody to LPS significantly
      abrogated the chemotactic activity of bacterial cells (P<0.001). Our findings
      provide evidence that IL-8 during eye closure, and bacterial chemotactic
      substances and LTB4 during contact lens induced adverse responses, are
      responsible for the recruitment of PMNs.

PMID- 9533840
TI  - The Von Sallmann Lecture 1996: an ophthalmological explanation of REM sleep.
AB  - The hypothesis is advanced that the purpose of the eyeball movements during REM
      sleep is to stir the aqueous humor behind the closed lids and so avoid the risk
      that its stagnation could cause corneal anoxia. The relevance of the hypothesis
      to evolutionary biology and intensive care nursing is discussed.

PMID- 9533841
TI  - An oneiropenic account of an ophthalmological career.
AB  - The author has done pretty much what he wanted to do throughout his professional
      life. Little harm resulted. A few findings may survive.

PMID- 9533842
TI  - Two spectral types of retinal light damage occur in albino as well as in
      pigmented rat: no essential role for melanin.
AB  - Earlier we showed that two spectral types of retinal damage occur in the
      pigmented rat. In the present study we investigated whether the same is true for
      albino rats. When investigating this issue we implicitly investigated the role of
      melanin in both damage types. An albinotic (Wistar) and a pigmented (Long Evans)
      strain of rats were used. Under anesthesia, a small part of the retina was
      irradiated at either 380 nm or at 470 nm. Three days later, the retina was
      analysed by funduscopy and prepared for light microscopy. Funduscopy showed no
      signs of damage in the albinotic retina. In the pigmented retina a decoloration
      of the fundus was noticed after irradiations starting from retinal doses of 0.6+/
      0.1 J cm-2 at 380 nm, and from 489+/-71 J cm-2 at 470 nm. By light microscopy,
      retinal damage was found in the albino retina. The histologic manifestations at
      380 nm differed from those at 470 nm. Irradiation at 380 nm at a dose of 0. 5-0.9
      J cm-2 damaged a few scattered photoreceptor cells. At doses of 1.2-1.6 J cm-2
      all rods were damaged, while the other retinal layers showed no changes. These
      findings were similar to those found at 380 nm in the pigmented rat. At 470 nm,
      damage was found most prominently in the retinal pigment epithelium. These cells
      showed swelling and an increased number of dark inclusions. Threshold damage
      occurred at doses of 250-500 J cm-2. Again, the pathology in the pigmented rat
      was highly similar to that in the albino rat. The results show that both spectral
      damage types occur in albino as well as in pigmented retina. Therefore, melanin
      plays no crucial role in these light damage types.

PMID- 9533843
TI  - Visual influences on diurnal rhythms in ocular length and choroidal thickness in
      chick eyes.
AB  - Recent investigations have raised the possibility that ocular diurnal rhythms
      might be involved in the regulation of eye growth. Specifically, the chick eye
      elongates with a daily rhythm, said to be absent in form-deprived eyes. The
      present study asks: (1) Which components of the eye have daily rhythms-only the
      overall eye size, or also choroidal thickness or anterior chamber depth? (2) Does
      the phase or amplitude of these rhythms differ in eyes growing either faster than
      normal (form-deprived eyes) or slower than normal (eyes recovering from form
      deprivation myopia)? Using high-frequency A-scan ultrasonography that allowed
      fine (8-20 micron) resolution of anterior chamber depth, vitreous chamber depth,
      choroidal thickness and axial length, we measured normal eyes, form-deprived eyes
      and eyes recovering from form-deprivation myopia at 6 hour intervals for 5 days
      and 4 nights. All eyes showed daily rhythms in axial elongation and choroidal
      thickness. In both normal and form-deprived eyes, the axial length was greatest
      in the afternoon when the choroid was thinnest, and hence, these rhythms were
      approximately in anti-phase to one another; in addition, there is some evidence
      that the axial length rhythm in form-deprived eyes is phase-advanced relative to
      that of their fellow control eyes. The amplitude of the rhythm in choroidal
      thickness in form-deprived eyes was significantly larger than in normal eyes. In
      recovering eyes in which elongation is slowed, the rhythm in axial length was
      significantly phase-delayed relative to normal eyes (peak at 8 pm) and the rhythm
      in choroidal thickness was phase-advanced (peak at 8 pm); thus in these eyes, the
      two rhythms are in phase. In these eyes, the choroids were thickening by
      approximately 100 micron/day. In all three groups, the rhythm in anterior chamber
      depth appears to differ in phase from the rhythm in axial length (and hence from
      the rhythm at the posterior wall of the eye). We propose that the phase
      relationship between these choroidal and eye length rhythms influence the rate of
      growth of the eye, and conclude that diurnal ocular rhythms may be important in
      eye growth regulation.

PMID- 9533844
TI  - The circadian rhythm in intraocular pressure and its relation to diurnal ocular
      growth changes in chicks.
AB  - Recent investigations have shown that growing chicken eyes elongate during the
      day and shorten during the night. We asked whether the chick, like a number of
      other animals, exhibits a rhythm in intraocular pressure (IOP) and whether this
      rhythm might be associated with this rhythm in elongation. We find that the
      intraocular pressure in normal eyes is high during the day and low in the middle
      of the night, similar to the rhythm in ocular elongation. The amplitude of this
      rhythm in IOP is approximately 8 mm Hg; it persists in constant darkness, albeit
      with a reduced amplitude, implying that the rhythm has a circadian component.
      Form deprivation by translucent diffusers does not affect the amplitude of the
      rhythm in IOP, but makes the phase of the rhythm more variable, such that the
      trough no longer consistently occurs at night. We find that the magnitude of the
      ocular compliance (the change in length induced by change in intraocular
      pressure) is consistent with the possibility that the diurnal changes in IOP
      might, through mechanical stretch, account for much of the diurnal changes in
      length. However, in individual eyes, we find consistent phase differences between
      the rhythms in IOP and ocular elongation. Therefore, we propose that the rhythm
      in IOP influences ocular elongation in ways other than by simply inflating the
      eye, for example, by influencing underlying rhythms in scleral extracellular
      matrix production. We conclude that the rhythm in IOP plays a role in the
      regulation of the growth of the eye.

PMID- 9533846
TI  - Transferrin in after-cataract and as a survival factor for lens epithelium.
AB  - The Fe-transport protein, transferrin (Tf), is synthesized and secreted by whole
      lenses and cultured lens epithelial cells. Because of Tf's central role in cell
      growth and proliferation, its participation in lens cell proliferation following
      cataract extraction was explored using a rabbit model of after-cataract. Varying
      amounts of the central anterior lens capsule were removed (0, 35, or 80%)
      following extraction of the lens. The Tf content of and secretion by after
      cataract lens capsular sacs containing regenerated lens tissue was determined ex
      vivo at 0, 3, 5, 7 and 9 weeks post-surgery. In all cases Tf content of and
      secretion by the lens sacs was higher than that of their contralateral controls
      (whole lenses). Tf secretion was up to 5-fold higher and metabolic labeling
      studies indicated secretion of newly synthesized Tf. The sacs contained up to 10
      times the concentration of Tf as the control lenses. Human lens after-cataract
      capsular bags also secreted Tf. The function of Tf as a survival factor was
      tested on cultured lens epithelial cells. Cells cultured in serum-free medium had
      a survival rate of only 20-34% if the medium was changed each day. If the medium
      was never changed during this period, the survival rate was 43-52%, suggesting
      secretion of essential growth factors by these cells. Addition of 200 microg ml-1
      Tf to the medium during each daily change increased survival to levels attained
      when the medium was not changed. Addition of Tf antibodies to the culture medium
      during each daily change decreased cell survival to 14%. Apparently Tf acts as a
      survival factor for lens epithelia and its synthesis is up-regulated in after
      cataract lens sacs. These factors suggest that Tf may play an important role in
      the pathogenesis of lens epithelial cell proliferation and after-cataract
      formation following cataract surgery.

PMID- 9533845
TI  - Ocular axial length and choroidal thickness in newly hatched chicks and one-year
      old chickens fluctuate in a diurnal pattern that is influenced by visual
      experience and intraocular pressure changes.
AB  - Low coherence laser Doppler interferometry (LDI) allows high precision
      measurements of the axial length of the eye and of the thickness of the
      individual layers of the ocular fundus. Here, we used LDI to monitor diurnal
      changes in these dimensions in eyes of newly hatched chicks and one-year-old
      chickens with normal or altered visual input. In chicks and chickens with normal
      visual experience, axial eye length displays diurnal fluctuations increasing
      during the light phase. Choroidal thickness also exhibits a diurnal pattern,
      shrinking during the day and expanding during the night. Retinal thickness does
      not vary. Based on the pressure compliance of the enucleated chick eye, the
      diurnal intraocular pressure (IOP) fluctuation could contribute both to the
      increase in axial length and to daytime choroidal shrinkage. Following
      deprivation of form vision by unilateral goggle wear, occluded chick eyes
      demonstrate enhanced axial elongation. Diurnal fluctuations in axial length but
      not in choroidal thickness are temporarily disrupted. The retina of form deprived
      eyes thins approximately 10% in five days. In contralateral eyes, the diurnal
      patterns of both axial length and choroidal thickness fluctuations are also
      disrupted. Following occluder removal in chicks, choroidal thickness increases
      for several days during both the light and dark phase, leading to its overall
      expansion. Retinal thickness returns to baseline. When deprived of form vision
      for five days, the eyes of year-old chickens do not exhibit measurable axial
      elongation. Diurnal patterns of fluctuation in axial length and choroidal
      thickness are however disrupted. After goggle removal, axial length fluctuation
      is restored to normal, but the diurnal choroidal thickness pattern is inverted.
      In contralateral eyes, choroidal thickness exhibits normal diurnal fluctuations
      both during and after form vision deprivation. In conclusion, axial length and
      choroidal thickness fluctuations are influenced by visual experience in both
      newborn chicks and one-year-old chickens. In selected instances a binocular
      interaction regarding axial length and choroidal thickness changes is suggested,
      the effect weakening with age.

PMID- 9533847
TI  - Dose-dependent prevention of sugar cataracts in galactose-fed dogs by the aldose
      reductase inhibitor M79175.
AB  - Sugar cataracts rapidly develop in dogs fed a diet containing 30% galactose.
      While studies on the formation and progression of these sugar cataracts suggest
      that they are osmotic in nature and are linked to aldose reductase, sugar
      cataract formation in the dog to date has not been completely prevented by the
      administration of aldose reductase inhibitors sorbinil and M79175. To demonstrate
      that the formation and progression of sugar cataracts in galactose-fed dogs can
      be dose-dependently inhibited by the administration of aldose reductase
      inhibitors, 9-month old male beagles were placed on diet containing 30% galactose
      with/without 10 or 16 mg kg-1 day-1 of M79175 for up to 39 months. Cataract
      progression in all dogs was followed by periodic slit lamp examination and
      documented by retroillumination photography. Although large variations in
      cataract formation and progression were observed, all dogs fed a 30% galactose
      diet for 39 months developed cataracts. Lens changes were significantly less in
      galactose-fed dogs treated with either 10 or 16 mg kg-1 M79175 and no cataract
      formation was observed in 3 of 6 galactose-fed dogs treated with 16 mg kg-1
      M79175. These observations confirm that aldose reductase plays a key role in
      initiating cataract formation in galactose-fed dogs and that cataract formation
      can be prevented by adequate inhibition of aldose reductase.

PMID- 9533848
TI  - Optimization of non-isotopic in situ hybridization: detection of the Y chromosome
      in paraformaldehyde-fixed, wax-embedded cat retina.
AB  - A technique was developed to detect the Y chromosome in paraformaldehyde-fixed
      diethylglycoldiesterate-embedded cat retina. The Y chromosome specific DNA probe
      was labeled with digoxigenin through polymerase chain reaction incorporation.
      After treatment of paraformaldehyde-fixed, diethylglycoldiesterate-embedded
      tissue sections with deoxyribonucleic acid decondensation and proteolytic
      digestion, non-fluorescent, non-isotopic in situ hybridization was performed on
      the retina sections. Most extensive treatment was required for the outer nuclear
      layer while the inner nuclear layer required more extensive treatment than the
      retinal pigment epithelial cells. Under optimal pretreatment conditions, the male
      cat retina displayed black spots which specifically localized at the periphery of
      the nuclei, while the female cat retina showed negative staining for the Y
      chromosome specific probe. The technique allows observation of the Y chromosome
      signal with preservation of retinal morphology and thus may be a valuable tool to
      discriminate donor cells in retinal pigment epithelial cell and photoreceptor
      cell transplants.

PMID- 9533849
TI  - Some kinetic properties of lactate dehydrogenase activity in cell extracts from a
      mammalian (ovine) corneal epithelium.
AB  - The purpose of the following study was to examine the kinetic properties of
      lactate dehydrogenase (LDH) in cell extracts of corneal epithelium. The
      epithelium, from quality- and size-selected ewe corneas, was dispersed in 10 mM
      Trizma maleate with or without sucrose at pH 7.0 and cell fractions obtained by
      homogenisation and differential centrifugation for evaluation of LDH at 37
      degrees C. Pyruvate-dependent oxidation of NADH was optimal at pH 6.5, while
      lactate-dependent reduction of NAD was optimal at pH 9.5; the former activity
      averaged 3 to 3.5 fold higher than the latter. NADPH and NADP were poor
      cofactors. The apparent Km values for pyruvate and lactate were 99 micromoles and
      3.9 millimoles respectively. At pH 6. 5, substrate inhibition was observed with
      pyruvate in excess of 0.25 mm with 50% activity measured at 1.2 mm. Excess
      substrate effects were not seen with lactate at pH 9.5, but pyruvate inhibited
      lactate-dependent reduction of NAD with 50% activity measured at 1.1 mm.
      Differential centrifugation confirmed that the activity was predominantly
      localised in the soluble (post mitochondria-lysosome) fraction of the cells.

PMID- 9533850
TI  - Hyaluronan in the interphotoreceptor matrix of the eye: species differences in
      content, distribution, ligand binding and degradation.
AB  - Hyaluronan (HA) distribution in the posterior eye wall from the vitreous through
      the sclera, with special consideration to localization in the retina and
      interphotoreceptor matrix (IPM), was evaluated in human, bovine, guinea pig, dog,
      rat and mouse tissues using a specific probe for HA (bHABC, biotinylated
      hyaluronan binding complex). The sclera, some regions of the choroid and vitreous
      body was positive for HA, as was the basal lamina of the retina (inner limiting
      membrane). bHABC binding was detected in the IPM of all species studied except
      the mouse. Predigestion with Streptomyces hyaluronidase for 3 hr before bHABC
      application eliminated binding in the vitreous, choroid, sclera and basal lamina
      of the retina, but did not eliminate bHABC binding in the IPM. In tissues from
      all species studied, incubation for 6 hr with hyaluronidase eliminated bHABC
      binding in the IPM, except for two human samples. In these two human samples, HA
      specific binding in the IPM persisted even after 24 hr enzyme treatment. bHABC
      failed to bind to any tissue layer when bHABC was preincubated with hyaluronan
      oligosaccharides before application. The resistance of the IPM HA to
      hyaluronidase digestion may reflect extensive coverage of HA binding sites by
      ligands present in this compartment which hinder enzyme access. The absence of
      bHABC binding to the IPM when the probe is preincubated with HA oligosaccharides
      indicates that the binding reflects specific interaction with HA. We conclude
      that, with the exception of the mouse, HA is a prominent constituent of the IPM,
      where it may serve to organize the matrix by functioning as a basic scaffold to
      which other macromolecules in the insoluble IPM are attached.

PMID- 9533851
TI  - Soluble expression in E. coli of a functional interphotoreceptor retinoid-binding
      protein module fused to thioredoxin: correlation of vitamin A binding regions
      with conserved domains of C-terminal processing proteases.
AB  - The exchange of all-trans retinol and 11-cis retinal between the photoreceptors
      and retinal pigmented epithelium is mediated by interphotoreceptor retinoid
      binding protein (IRBP). IRBP contains binding sites for retinoids,
      docosahexaenoic acid and probably cell surface and matrix receptors. IRBP arose
      through the quadruplication of an ancient protein, represented by its carboxy
      terminal module (module 4 in amphibians and mammals). Module 4 has retinol
      binding activity and is composed of regions coded for by each of IRBP's four
      exons. Determining the function of the exons has been hampered by insoluble
      expression of module 4 in Escherichia coli. Here, we found that module 4 of
      Xenopus IRBP (X4IRBP), as well as its exon segments, can be expressed in a
      soluble form as thioredoxin fusion proteins. The recombinant proteins were
      purified by ion exchange and arsenical-based affinity chromatography. Liquid
      chromatography/mass spectrometry confirmed that the sequence of X4IRBP is
      correct. All-trans retinol binding was characterized by monitoring enhancement of
      retinol fluorescence, quenching of intrinsic protein fluorescence, and transfer
      of energy to the bound retinol. Retinol bound to X4IRBP at 2.20+/-0.29 sites with
      a KD=1.25+/-0.39. One of the two sites was localized to Exons(2+3) and had a
      KD=0.26+/-0.13 micron. This site, which supported protein quenching and energy
      transfer, probably contains at least one of the two conserved tryptophans present
      in this segment. The second site was localized to Exon 4. This site supported the
      enhancement of retinol fluorescence but not protein quenching or energy transfer
      and had a KD=1.94+/-0.20 micron. Exon 1 had no retinol binding activity. The
      location of the retinol binding regions correlated with the distribution of
      domains conserved between IRBPs and the newly recognized family of C-terminal
      processing proteases (CtpAs), proteins which bind and cleave non-polar carboxy
      termini.

PMID- 9533852
TI  - Quantitation of specific cleavage sites at the C-terminal region of alpha-A
      crystallin from human lenses of different age.

PMID- 9533853
TI  - Extralenticular expression of the rodent betaB2-crystallin gene.

PMID- 9533854
TI  - Announcements 

PMID- 9533855
TI  - Modulation of chloride secretion across the pigmented rabbit conjunctiva.
AB  - The purpose of the present study was to investigate whether active Cl- secretion
      in the pigmented rabbit conjunctiva was subject to cAMP, Ca2+ and protein kinase
      C (PKC) modulation. The excised pigmented rabbit conjunctivas were mounted in the
      modified Ussing-type chambers for measurement of unidirectional 36Cl fluxes under
      the open-circuit condition and of the short-circuit current (Isc), potential
      difference, and transconjunctival electrical resistance. The results indicate
      that Cl- secretion across the conjunctiva was abolished by mucosal application of
      1 mM N-phenylanthranilic acid and was reduced by 40% by serosal application of 10
      microM bumetanide. Net Cl- flux was stimulated by 133% by 1 mM 8-Br cAMP, 107% by
      10 microM A23187, and 87% by 1 microM phorbol 12-myristate-13-acetate (PMA),
      suggesting that cAMP, Ca2+, and PKC all modulated active Cl- secretion,
      respectively. There existed a linear correlation between measured changes in net
      Cl- flux and observed changes in Isc (r2=0.99). The serial treatment of the
      conjunctiva with (a) 1 mM 8-Br cAMP and 10 microM A23187 and (b) 10 microM A23187
      and 1 microM PMA resulted in sequence-independent, additive stimulation of Isc.
      In the case of 1 mM 8-Br cAMP and 1 microM PMA, additive stimulation of Isc was
      observed only when 1 mM 8-Br cAMP was added prior to 1 microM PMA. These results
      suggest that a given pharmacological agent may affect more than one channel type
      and that there might be a possible connection among the channels at the signal
      transduction level. In summary, Cl- appears to enter the pigmented rabbit
      conjunctiva from the serosal fluid via Na+-(K+)-2Cl- cotransport process and exit
      to the mucosal fluid via channels, resulting in active Cl- secretion. Active Cl-
      secretion in the pigmented rabbit conjunctiva appears to be modulated by cAMP,
      Ca2+, and PKC.

PMID- 9533856
TI  - Immunolocalization of prolyl 4-hydroxylase subunits, alpha-smooth muscle actin,
      and extracellular matrix components in human lens capsules with lens implants.
AB  - Lens capsules become fibrotic after the extraction of a cataract. To understand
      this phenomenon, we evaluated the immunolocalization of prolyl 4-hydroxylase (an
      enzyme involved in procollagen hydroxylation), and extracellular matrix
      components and cytoskeletal components in a normal human lens capsule and in
      others with intraocular lenses. Lens capsules containing intraocular lenses were
      removed from a patient with proliferative vitreoretinopathy and three with
      proliferative diabetic retinopathy during vitreous surgery. Two circular sections
      of the anterior capsules with lens epithelial cells were obtained by anterior
      capsulotomy during cataract surgery. In addition, a lens capsular bag was
      obtained immediately after phacoemulsification. The lens capsules were processed
      for light microscopic immunohistochemical detection of the alpha and beta
      subunits of prolyl 4-hydroxylase, extracellular matrix components (including
      collagen types, laminin and cellular fibronectin) or cytoskeletal components
      (such as cytokeratin, vimentin and alpha-smooth muscle actin). Monolayer lens
      epithelial cells were seen on the inner surface of the normal anterior capsules.
      Each intraocular lens was found to be fixed in the capsular bag. Light
      microscopic immunohistochemistry showed that these proliferating cells expressed
      vimentin and alpha-smooth muscle actin; in contrast, quiescent lens epithelial
      cells did not stain for alpha-smooth muscle actin. Marked immunostaining for
      subunits of prolyl 4-hydroxylase was detected in lens epithelial cells
      proliferating on the capsules, while no or only faint prolyl 4-hydroxylase
      immunoreactivity was detected in quiescent lens epithelial cells immediately
      after phacoemulsification. Collagen types I, III and VI and cellular fibronectin
      were observed diffusely in accumulated connective tissue on a capsule with an
      intraocular lens. Type IV collagen immunoreactivity was seen both in the capsules
      and in the connective tissue accumulation on the capsules. Collagen V and laminin
      were detected in association with cellular proliferation. Collagen VII and VIII
      and laminin 5 were not seen. We concluded that during wound healing of the lens
      capsule after cataract extraction, the lens epithelial cells that proliferate on
      the inner surface of the capsule transform it into a myofibroblastic phenotype,
      expressing prolyl 4-hydroxylase and alpha-smooth muscle actin. These
      proliferating cells are involved in the production of collagen on the lens
      capsule. This results in a postoperative fibrotic process and contraction of the
      lens capsule.

PMID- 9533857
TI  - Rhodopsins from three frog and toad species: sequences and functional
      comparisons.
AB  - The frequency of thermal 'dark events' in the membrane current of rhodopsin rods
      of the bullfrog, Rana catesbeiana, is considerably lower than observed in rods of
      two toad species, even though all three rhodopsins have approximately the same
      absorbance characteristics. In order to map amino acid substitutions possibly
      associated with thermal stability in the genus Rana, the cDNA's coding for the
      rhodopsins of Bufo bufo, B. marinus and R. temporaria were sequenced and the
      conceptually translated protein sequences aligned to the previously sequenced
      rhodopsins of R. catesbeiana, R. pipiens and Xenopus laevis. Across the six
      anuran species studied, there are sixteen non-conserved substitutions and six
      changes that include gain or loss of a hydroxyl group. Serine or threonine at
      position 220 is unique to the three Rana species, phenylalanine at position 270
      is unique to all three Ranas and to X. laevis, and phenylalanine at position 274
      is unique to both species of the genus Bufo. This investigation produces a list
      of substitutions that are candidates for future studies of thermal stability. In
      addition, a number of amino acids are identified that apparently do not influence
      absorbance characteristics, at least not cumulatively.

PMID- 9533858
TI  - Co-localization of the insulin receptor, jun protein and choline
      acetyltransferase in embryonic chick retina.
AB  - Previous work demonstrated that the availability of insulin to the embryonic
      chick retina at a critical developmental stage stimulated the activity of the
      acetylcholine synthetic enzyme, choline acetyltransferase (ChAT) and that this
      increase required the AP-1 transcription factor, c-jun. Here it is shown that
      immediately following a 2-5 min exposure to insulin there is, in the amacrine and
      ganglion cells of the chick embryo retina, a transient increase in the level of
      jun protein followed by a long-lasting increase in ChAT. These and previous
      results show that insulin receptor activation is necessary for the characteristic
      retina developmental increase in ChAT protein and that this increase is preceded
      by a transient increase in the synthesis of the transcription factor c-jun in the
      same retina cells. The data demonstrate an intracellular signal transduction
      pathway from the developmentally-activated insulin receptor through c-jun to ChAT
      and cholinergic differentiation.

PMID- 9533859
TI  - Endogenous nucleosides in the guinea-pig eye: analysis of transport and
      metabolites.
AB  - This study investigates the transport of endogenous nucleosides and
      deoxynucleosides from the capillaries of the eye into the aqueous humour and the
      lens using the in situ vascular eye perfusion technique in the guinea-pig. The
      transport of [3H] adenosine and [3H] thymidine across the blood-aqueous barrier
      proved to be very rapid with a volume of distribution after 4 minutes perfusion
      reaching 11.9+/-3.0% and 9.93+/-1.1%, respectively. However, the transport of
      [3H] guanosine and [3H] cytidine was slower, with volumes of distribution
      reaching only 3.38+/-0.58% and 4.8+/-1.41%. The values for the entry of
      deoxyadenosine and deoxyguanosine were not significantly different from the
      values obtained for corresponding ribonucleosides (adenosine and guanosine) so
      that a change in the pentose sugar does not change the affinity of the nucleoside
      for the transport protein. Perfusion with a low sodium medium inhibited the
      transport of [3H] adenosine and [3H] thymidine into the aqueous humour. The
      presence of 800 nM NBTI also caused a decrease in adenosine transport into the
      aqueous humour, so that the volume of distribution after 2 minutes reached only
      3.78+/-1.87%. These findings suggest that the transfer of adenosine across the
      blood-aqueous barrier has both concentrative and equilibrative components. The
      presence of 0.1 mM thymidine had no effect on the [3H] adenosine transport,
      whereas 0.1 mM of adenosine resulted in a marked decrease on the [3H] thymidine
      transport which suggests that the concentrative nucleotide transport is probably
      mediated by both cif and cit transport systems. The cellular uptake of
      nucleosides into the lens was very rapid and the volume of distribution of purine
      nucleosides was within the range of 30-50% whereas that for thymidine uptake was
      somewhat lower, reaching 20-30%. HPLC analysis of the eye structures in the
      guinea-pig showed that lens, vitreous body and the rest of the eye do not contain
      either free nucleosides or purine bases in detectable quantities, except for
      xanthine which was detected in aqueous humour at a concentration of 2.51+/-0.51
      mM. However, serum of the anaesthetised guinea-pig did not contain xanthine in
      detectable amount so it seems that the metabolic degradation of the nucleosides
      in the guinea-pig eye progresses as far as xanthine, which is then accumulated in
      the aqueous humour.

PMID- 9533860
TI  - Dexamethasone and dexamethasone phosphate detected by 1H and 19F NMR spectroscopy
      in the aqueous humour.
AB  - To apply nuclear magnetic resonance (NMR) spectroscopy to study the penetration
      of dexamethasone phosphate into the aqueous humour from rabbit following topical
      administration. After topical administration of 0.1%, 1.0% and 10% dexamethasone
      phosphate solutions, respectively, samples of aqueous humour were aspirated,
      freeze-dried, redissolved in deuterium oxide and analyzed by high resolution 1H
      and 19F NMR spectroscopy. In order to study the lipophilic and hydrophilic
      metabolites of the drug, samples obtained after application of 1% dexamethasone
      phosphate were extracted with methanol/chloroform, and then extracted with
      perchloric acid. In all samples obtained from eyes denuded of the corneal
      epithelium prior to administration of dexamethasone, signals corresponding to the
      chemical shifts of the drug were identified in 19F NMR spectra. In the
      experiments performed with 1% dexamethasone phosphate, both dexamethasone and
      dexamethasone phosphate were detected in the aqueous humour. Using 10%
      dexamethasone phosphate solutions, signals from the drug were detected in 1H NMR
      spectra simultaneously with signals from about twenty other substances present in
      the aqueous humour. NMR spectroscopy appears to be a valuable method for studying
      dexamethasone metabolism and penetration into ocular tissues. It provides
      simultaneous detection of both the drug metabolites and other substances in the
      sample and might offer a complementary approach to other analytical methods.

PMID- 9533861
TI  - Gene expression of the proteasome in rat lens development.
AB  - To study the involvement of the proteasome in ocular lens cell proliferation and
      differentiation, a partial cDNA encoding rat S7, a subunit of the ATPase complex
      that regulates the 20S proteasome (multicatalytic proteinase complex), and RC3, a
      subunit of the 20S proteasome moiety, were cloned and used to compare relative
      levels of S7 and RC3 mRNAs. mRNA was measured, using a competitive RT-PCR assay,
      in isolated lens cells or explant cultures induced to differentiate or
      proliferate. During differentiation, S7 mRNA levels increased (1.7 fold) and RC3
      mRNA levels remained the same compared to mRNA in quiescent cells. During
      proliferation, RC3 mRNA levels were elevated (2 fold) and S7 mRNA levels remained
      the same. This demonstrated that representative proteasome and ATPase complex
      mRNA levels are regulated differentially during differentiation and
      proliferation. The maintenance of proteasome subunit mRNA and increase in ATPase
      complex subunit mRNA observed in differentiating lens cells is in contrast to the
      patterns of expression that have been reported for other differentiating cells,
      which down-regulate the 20S and/or 26S proteasome. This suggests that the role of
      the proteasome in cell development is cell specific.

PMID- 9533862
TI  - Inwardly rectifying potassium channels in lens epithelium are from the IRK1 (Kir
      2.1) family.
AB  - Lens epithelial cells from many species contain inwardly rectifying K+ channels.
      The channels are highly selective for K+ over Na+. They have a conductance of 27
      30 pS in symmetrical 150 mM K+ solutions. The conductance to inwardly flowing
      current depends on the external [K+], being 1/2 maximal at about 50 mM and
      maximal by 110-150 mM. The amino acid sequences from lens epithelium (eight
      different species) show at least 98% sequence homology to each other and to the
      potassium channel known as IRK1 (Kir 2.1). Cloned channels from chick, rabbit,
      and human lens epithelium all make functional channels when their cDNA is
      transfected into HEK-293 or tsA-201 cells. Human lens inward rectifiers when
      engineered as fusion proteins with green fluorescent protein (GFP) also make
      functional channels. In addition, their localization in the membrane and in
      intracellular organelles can be demonstrated by fluorescence microscopy.

PMID- 9533863
TI  - Regulation of homeobox-containing genes during lens regeneration.
AB  - In this study, the expression of homeobox-containing genes was evaluated after
      lentectomy in the newt, which is competent for lens regeneration, and in the
      axolotl which is not. Such a comparison was designed to offer insights about
      possible regulation due to regenerative abilities. Six homeobox-containing genes
      were examined: NvHox A4, NvHox B1, NvHox 7, NvHox X, Nvmsx-1 and Xbr1. For all
      genes examined, it was found that soon after lentectomy in the newt there was a
      general down-regulation in the retina. This down-regulation varied among the Hox
      genes with NvHox 7 and NvHox B1 being virtually absent in the initial stages;
      their expression was re-established to the original levels after the reappearance
      of lens. The expression patterns, for NvHox 7 and NvHox B1 were the same when the
      lens was removed and then displaced. However, in axolotl, down-regulation was not
      observed. These data suggest that the observed regulation is related to the
      process of lens regeneration and provide the first molecular evidence that lens
      regeneration could be dependent on retina and underline the importance of this
      tissue in lens regeneration. Such patterns link expression of homeobox-containing
      genes and lens regeneration and can be now used to understand the underlying
      mechanisms of lens regeneration and transdifferentiation.

PMID- 9533864
TI  - Nuclear degeneration in the developing lens and its regulation by TNFalpha.
AB  - DNA fragmentation in lens fibre cell nuclei undergoing programmed degeneration
      was identified by terminal deoxynucleotidyl transferase (TdT)-mediated biotin
      dUTP nick end labelling (TUNEL). Lens epithelial cells in culture were induced to
      differentiate into lens fibre-like clumps of cells (lentoids) by insulin and it
      was shown that the TUNEL method was also an effective means of labelling
      degenerating nuclei in lentoid cells in lens epithelial cell cultures. Using
      immuno-fluorescence and confocal microscopy, it was shown that TNFalpha and TNF
      receptor (TNFR1, and TNFR2) immunoreactivity was present in sections of chick
      embryo lenses. TNFalpha immunoreactivity was associated with the lens epithelium
      and lens fibres. TNFR1 immunoreactivity was present in lens epithelial cells,
      cortical lens fibres, and lens fibre cell nuclei, while TNFR2 immunoreactivity
      had a similar distribution to that of TNFR1, but was not associated with nuclei.
      Similar patterns of TNFalpha, TNFR1, and TNFR2 immunoreactivity were observed in
      lens epithelial cell cultures. When added to lens epithelial cell cultures,
      TNFalpha, at concentrations of 50 to 100 ng ml-1, and agonistic antibodies to
      both TNFR1 and TNFR2 significantly (P<0.05) enhanced the number of degenerating
      (TUNEL-positive) nuclei. On the other hand, a neutralising antibody to TNFalpha
      significantly (P<0. 05) reduced the number of TUNEL-positive nuclei. These
      results demonstrate that TUNEL is an effective means of labelling degenerating
      lens fibre nuclei during lens fibre and lentoid differentiation, and suggest a
      potential role for TNFalpha-like factors and their receptors in the degeneration
      of lens fibre cell nuclei during lens differentiation. We further suggest that
      the nuclear degeneration of lens fibre cells is analogous to the nuclear events
      that occur during apoptosis, and that in lens cells the nuclear degeneration is
      uncoupled from the plasma membrane events of apoptosis that normally lead to cell
      death.

PMID- 9533865
TI  - Announcements 
AB  - No abstract.

PMID- 9533866
TI  - Model studies of the role of mechano-sensitive currents in the generation of
      cardiac arrhythmias.
AB  - Mechano-electrical feedback is studied by incorporating linear, instantaneously
      activating mechano-sensitive conductances into single cardiac cell models, as
      well as one- and two-dimensional cardiac network models. The models qualitatively
      reproduce effects of maintained mechanical stretch on experimentally measured
      action potential characteristics such as amplitude, maximum diastolic potential,
      peak upstroke velocity, and conduction velocity. Models are also used to simulate
      stretch-induced depolarizations, action potentials, and arrhythmias produced by
      pulsatile volume changes in left ventricle of dog. The mechano-sensitive
      conductance threshold for a stretch-induced action potential is closely related
      to the magnitude of the time-independent K+ current, IK1, which offsets inward
      mechano-sensitive current. Activation of mechano-sensitive conductances in small,
      spatially localized region of cells can evoke graded depolarizations, propagating
      ectopic beats, and if timed appropriately, spiral reentrant waves. Mechano
      sensitive conductance changes required to evoke these responses are well within
      the physiologically plausible range. Results therefore indicate that many mechano
      electrical feedback effects can be modeled using linear, instantaneously
      activating mechano-sensitive conductances. As an example of how stretch can occur
      in real human hearts, magnetic resonance images with saturation tagging are used
      to reconstruct the three-dimensional left ventricular wall motion. In patients
      with infarcts or recent ischemic events, "paradoxical deformation" is observed in
      that regions of myocardium are stretched rather than contracted during systole.
      In contrast, normal hearts contract uniformly with no stretch during systole.
      Paradoxical deformations in ischemic hearts may therefore present one possible
      substrate for the mechanically induced arrhythmias modeled above.

PMID- 9533867
TI  - Ecological mechanisms of evolution by natural selection: causal processes
      generating density-and-frequency dependent fitness.
AB  - The current theory of natural selection explains that adaptive evolution occurs
      because genotypes with greater survival or reproductive tendencies, due to their
      particular biological properties, tend to increase in frequency over the lesser
      ones in a common environment; therefore, the former will eventually replace the
      latter. In nature, such a selection process most often occurs in a local
      population which is nested in a community involving local ecological dynamics
      which are not clearly articulated in the explanatory scheme of the theory. This
      paper seeks to explicate such an ecological process giving rise to the evolution
      of a local population with a particular focus on dynamic effects of an increase
      in the number of invasive, new types on the fate of old ones. Arguments using the
      ecological-mechanistic model, representing negative interactions among
      alternative types of organisms, suggest major ecological mechanisms by which the
      new replace the old; a selective increase in the number of one type leads to a
      decrease in the equilibrial abundance of a limiting resource, an increase in the
      density of conspecifics, and/or an increase in the density of predators, which
      would in turn lower the per capita reproductive rate, or raise the morality rate
      of another and make it extinct. Thus, replacement due to selection is associated
      with such dynamic shifts in equilibria occurring in a local community. The
      analysis of three (a resource, a prey and a predator) and four species (those
      plus a top predator) models suggests that evolutionary processes cannot be
      predicted without reference to the web structure of the community, that some
      fitness components causing a selective increase in a particular type can have, in
      some cases, nothing to do with factors causing selective decreases in
      alternatives, and that evolution of some traits can occur without resource
      competition.

PMID- 9533868
TI  - Analysis and application of an equilibrium model for in vitro bioassay systems
      with three components: receptor, hormone and hormone-binding-protein.
AB  - A simple theoretical framework is presented for bioassay studies using three
      component in vitro systems. An equilibrium model is used to derive equations
      useful for predicting changes in biological response after addition of hormone
      binding-protein or as a consequence of increased hormone affinity. Sets of
      possible solutions for receptor occupancy and binding protein occupancy are found
      for typical values of receptor and binding protein affinity constants. Unique
      equilibrium solutions are dictated by the initial condition of total hormone
      concentration. According to the occupancy theory of drug action, increasing the
      affinity of a hormone for its receptor will result in a proportional increase in
      biological potency. However, the three component model predicts that the
      magnitude of increase in biological potency will be a small fraction of the
      proportional increase in affinity. With typical initial conditions a two-fold
      increase in hormone affinity for its receptor is predicted to result in only a
      33% increase in biological response. Under the same conditions an 11-fold
      increase in hormone affinity for receptor would be needed to produce a two-fold
      increase in biological potency. Some currently used bioassay systems may be
      unrecognized three component systems and gross errors in biopotency estimates
      will result if the effect of binding protein is not calculated. An algorithm
      derived from the three component model is used to predict changes in biological
      response after addition of binding protein to in vitro systems. The algorithm is
      tested by application to a published data set from an experimental study in an in
      vitro system (Lim et al., 1990, Endocrinology 127, 1287-1291). Predicted changes
      show good agreement (within 8%) with experimental observations.

PMID- 9533869
TI  - Correlations in protein sequences and property codes.
AB  - Correlation functions in large sets of non-homologous protein sequences are
      analysed. Finite size corrections are applied and fluctuations are estimated. As
      symbol sequences have to be mapped to sequences of numbers to calculate
      correlation functions, several property codes are tested as such mappings. We
      found hydrophobicity autocorrelation functions to be strongly oscillating.
      Another strong signal is the monotonously decaying alpha-helix propensity
      autocorrelation function. Furthermore, we detected signals corresponding to an
      alteration of positively and negatively charged residues at a distance of 3-4
      amino acids. To look beyond the property codes gained by the methods of physical
      chemistry, mappings yielding a strong correlation signal are sought for using a
      Monte Carlo simulation. The mappings leading to strong signals are found to be
      related to hydrophobicity of alpha-helix propensity. A cluster analysis of the
      top scoring mappings leads to two novel property codes. These two property codes
      are gained from sequence data only. They turn out to be similar to known property
      codes for hydrophobicity or polarity.

PMID- 9533870
TI  - A model of disease and vaccination for infections with acute and chronic phases.
AB  - A general model is presented of a disease in which both recovered and vaccinated
      individuals are protected from acute disease, but are still susceptible to
      chronic infection. The special threshold conditions for the establishment and
      persistence of such a disease are derived and explained in full. The efficacies
      of alternative vaccination strategies are detailed and a specific example of such
      a disease is given by examining feline calicivirus (FCV), a cause of upper
      respiratory tract disease in cats.

PMID- 9533871
TI  - Telomere length distribution and Southern blot analysis.
AB  - Southern blot analysis of terminal restriction fragments (TRFs) is the standard
      method for quantitative examination of telomere length distributions. Since TRFs
      contain a subtelomeric component, central parameters of the TRF distribution n(L)
      such as the arithmetic mean (M) or the median (Me) cannot be derived directly
      from Southern blot data, i.e. from the optical density distribution OD(L).
      Several estimates have been applied instead; the seeming arithmetic mean A, the
      "center of mass" C, and the positions of maximal (P) and half-maximal optical
      density (P(1/2)). We show that C> A> M for any non-truncated distributions n(L),
      and P> M> P1/2 for any symmetrical unimodal n(L). Symmetric appearance on a
      Southern blot, however, suggests positive skewness of n(L). Thus, a lognormal
      form of n(L) may be considered. Then, C> A> M> P=Me> P(1/2). Alternatively, a
      Weibull distribution may be assumed. The latter is compatible with negative
      feedback-regulation of the telomere lengths. Using the maximum likelihood method
      we compare these distributions with FISH-data on telomere lengths in different
      cell types. The fit of the lognormal distribution is clearly superior. Lognormal
      genesis may relate to telomere breakage and recombination. Truncation of the
      upper end of the TRF distribution is possible due to Southern blot artifacts.
      Thereby, the order of the estimates may change to P> C> A. Having minimal
      sensitivity to truncation, P seems to be the optimal choice. however, the
      variability of P is high since peakedness of OD(L) and DNA length resolution are
      inversely related.

PMID- 9533872
TI  - On the origin of plasmid-borne, extended-spectrum, antibiotic resistance
      mutations in bacteria.
AB  - Many antibiotic resistance mutations arise in pathogenic bacteria that harbor
      plasmids (R-plasmids). Resistance to third generation cephalosporins, for
      instance, largely occurs by one or more point mutations in plasmid bla genes that
      expand the resistance spectrum of beta-lactamases. Here I review relevant
      evidence underlying the worldwide emergence of extended spectrum beta-lactamases
      (ESBLs). The conclusion reached is that the origin of these resistance-conferring
      mutations cannot be explained by a series of single point mutation and selection
      events. Instead, highly advantageous stochastic processes might exist that
      generate alterations in the sequence or the conformation of particular regions in
      chromosomal or plasmid genomes such as bla, i.e., recombination or mutation.
      Several explanations for the origin of ESBLs are reviewed but direct experimental
      evidence to support or to invalidate them is still lacking. The cellular
      conditions under which ESBLs arise are unknown; however, involvement of
      nutritional stresses inside natural animal hosts and of plasmid conjugal
      functions appear likely.

PMID- 9533873
TI  - The pinwheel experiment revisited.
AB  - The critical point hypothesis explains the origin of some cardiac arrhythmias,
      and the bidomain model describes electrical stimulation of the heart. In this
      paper, the critical point hypothesis is combined with the bidomain model. The
      result is four new predictions about the pinwheel experiment, a fundamental
      experiment in cardiac electrophysiology. These are: (1) The duration of the
      vulnerable period during cathodal S2 stimulation is longer for an S1 wavefront
      propagating perpendicular to the fibers than for an S1 wavefront propagating
      parallel to the fibers. (2) For anodal S2 stimulation with the S1 wavefront
      propagating parallel to the fibers, the vulnerable period splits into two periods
      with an "invulnerable period" between them. (3) For anodal S2 stimulation with
      the S1 wavefront propagating perpendicular to the fibers, the vulnerable period
      consists of only one period. (4) A previously suggested mechanism for the upper
      limit of vulnerability (S2 is so strong that the entire tissue is depolarized by
      an amount greater than S*) is no longer applicable.

PMID- 9533874
TI  - Announcement 
AB  - Copyright 1998 Academic Press Limited

PMID- 9533875
TI  - Site-directed mutagenesis supports a three-dimensional model of the runt domain.
AB  - The "runt domain" (RD) is a 128 amino acid region of the Drosophila pair-rule
      gene runt. This highly conserved region delineates the DNA-binding domain of a
      new family of transcription factors; the RD proteins. The family includes genes
      from Drosophila, chicken and mammals that are involved in a wide range of
      developmental processes, from sex determination and neurogenesis in Drosophila to
      hematopoiesis and osteoblast differentiation in mouse and human. The RD confers
      DNA binding ability and mediates the interaction of mammalian RD proteins with
      the beta-subunit (CBFbeta), which enhances the DNA binding. The primary sequence
      of RD shows no similarity to other known DNA-binding motifs and its three
      dimensional (3D) structure is not known. We employed molecular modeling-based
      mutagenesis to generate a 3D model of RD. Fold recognition programs identified
      the palm subdomain of rat DNA polymerase beta as the most likely fold for RD. In
      the predicted model, the RD region which interacts with DNA contains two arginine
      residues, R130 and R135, which appear to be in close contact with the major
      groove of the DNA and to interact with the three essential guanine bases of the
      core DNA motif PyGPyGGT. We mutated these two R residues and demonstrated that
      mutations markedly reduced the binding of RD to DNA with no effect on RD
      interaction with CBFbeta. The data provide important clues about the possible 3D
      structure of the RD and its interaction with the core DNA motif.

PMID- 9533877
TI  - Structural diversity of leucine-rich repeat proteins.
AB  - The superfamily of leucine-rich repeat proteins can be subdivided into at least
      six subfamilies, characterised by different lengths and consensus sequences of
      the repeats. It was proposed that the repeats from different subfamilies retain a
      similar superhelical fold, but differ in the three-dimensional structures of
      individual repeats. The sequence-structure relationship of three new subfamilies
      was examined by molecular modelling. I provide structural models for the repeats
      of all subfamilies. The models enable me to explain residue conservations within
      each subfamily. Furthermore, the difference in the packing explains why the
      repeats from different subfamilies never occur simultaneously in the same
      protein. Finally, these studies suggest different evolutionary origins for the
      different subfamilies. The approach used for the prediction of the leucine-rich
      repeat protein structures can be applied to other proteins containing internal
      repeats of about 20 to 30 residue in length.

PMID- 9533876
TI  - Unequal homologous recombination between LINE-1 elements as a mutational
      mechanism in human genetic disease.
AB  - Unequal homologous recombination between repetitive genetic elements is one
      mechanism that mediates genome instability. We have characterized a homologous
      recombination event between two neighboring LINE-1 sequences in the human gene
      encoding the beta subunit of phosphorylase kinase (PHKB). It has lead to the
      deletion of 7574 nucleotides of genomic DNA including exon 8 of this gene, giving
      rise to glycogen storage disease through phosphorylase kinase deficiency. To our
      knowledge, this is the first example of a mutation due to unequal homologous
      recombination between LINE-1 elements. The sequence features of the recombining
      LINE-1 elements and of the recombination junction site, and possible reasons for
      the more frequent occurrence of unequal homologous recombination between Alu
      elements are discussed.

PMID- 9533878
TI  - Epitope mapping of T4 endonuclease VII with monoclonal antibodies reveals
      importance of both ends of the protein for target binding.
AB  - Endonuclease VII (endo VII) of bacteriophage T4 is a Holliday-structure resolving
      enzyme that can also recognize many other defects in DNA via an altered secondary
      structure. The protein has a molecular mass of 18 kDa and exists as a dimer in
      solution. Here we report the production and characterization of monoclonal
      antibodies (mAbs) directed against the highly purified enzyme. From one fusion 15
      hybrid cell lines producing mAbs with high affinity for endo VII could be
      established. The mAbs were used for epitope mapping of the protein by using N
      terminal, C-terminal and internal peptides of endo VII as antigens in enzyme
      linked immunoabsorbant assays. Three classes of mAbs were distinguished as
      follows: (1) the predominant class with 13 mAbs recognized a C-terminal epitope
      located between amino acid residues 115 and 145; (2) a second class, represented
      by one mAb, recognized an epitope located at the N terminus between amino acid
      residues 16 and 65; (3) a third class, represented by one mAb, recognized an
      epitope built from nearly the entire native protein including amino acid residues
      from the C and N terminus of endo VII. The latter finding suggests close
      proximity of the two ends, which are provided apparently by the same monomer,
      since the mAb from class III does also react with a mutant protein deficient in
      dimerization. Internal sequences of endo VII between amino acid residues 78 and
      145 did not react with any of the mAbs.

PMID- 9533879
TI  - The largest (70 kDa) product of the bacteriophage T4 DNA terminase gene 17 binds
      to single-stranded DNA segments and digests them towards junctions with double
      stranded DNA.
AB  - Bacteriophage terminases are oligomeric multifunctional proteins that bind to
      vegetative DNA, cut it and, together with portal proteins, translocate the DNA
      into preformed heads. Most terminases are encoded by two partially overlapping
      genes. In phage T4 they are genes 16 and 17. We have shown before that the larger
      of these, gene 17, can yield, in addition to a full-length 70 kDa product,
      several shorter peptides. At least two of these, gene product (gp) 17' and gp17",
      are initiated in the same reading frame as the 70 kDa gp17 from internal ribosome
      binding sites. Most of the shorter gp17 s contain predicted ATPase motifs, but
      only the largest (70 kDa) peptide has a predicted single-stranded DNA binding
      domain. Here we describe the DNA binding and cutting properties of the purified
      70 kDa protein, expressed from two different clones containing gene 17 but no
      other T4 gene. Epitope-specific antibodies, which recognize several different
      gene 17 products in extracts of induced clones or of T4-infected cells,
      precipitate the purified 70 kDa gp17. When Mg2+ is chelated by EDTA this 70 kDa
      protein binds to single-stranded DNA, preferentially to junctions of single- and
      double-stranded DNA segments. It does not bind to blunt-ended double-stranded
      DNA. When Mg2+ is present the purified 70 kDa gp17 digests single-stranded
      segments preferentially up to junctions with double-stranded DNA. A 70 kDa gp17
      from a P379L temperature sensitive (ts) mutant, which has lost the nuclease and
      ATPase activities, retains the single-stranded DNA binding activity. Taken
      together with earlier findings these results support a model for packaging of T4
      DNA from single-stranded regions in recombinational or replicative intermediates,
      which occur at nearly random positions of the genome. This mechanism may be an
      alternative to site-specific initiation of packaging proposed by other
      investigators.

PMID- 9533880
TI  - Effects of mutations in the polymerase domain on the polymerase, RNase H and
      strand transfer activities of human immunodeficiency virus type 1 reverse
      transcriptase.
AB  - Based on structural analyses and on the behavior of mutants, we suggest that the
      polymerase domain of HIV-1 reverse transcriptase (RT) plays a critical role in
      holding and appropriately positioning the template-primer both at the polymerase
      active site and at the RNase H active site. For RT to successfully copy the viral
      RNA genome, RNase H must cleave the RNA with absolute precision. We believe that
      a combination of the structure of the template-primer and its precise positioning
      are responsible for the specific cleavages RNase H makes. We have proposed that
      resistance of HIV-1 RT to nucleoside analogs involves a subtle repositioning of
      the template-primer. This hypothesis is based on both structural and biochemical
      analyses. Mutations that confer resistance to nucleoside analogs do not cluster
      at the polymerase active site; however, they are in positions where they could
      alter the interaction between RT and the template-primer. If, as we have
      hypothesized, the polymerase domain is primarily responsible for positioning the
      template-primer and RNase H cleavage depends on this positioning, it should be
      possible to use RNase H cleavage to monitor at least some of the major changes in
      the position of the template-primer. We have used three assays (polymerase, RNase
      H, and strand transfer) to investigate the effects of mutations in the polymerase
      domain, including mutations that confer resistance to nucleotide analogs, on HIV
      1 RT. All three assays involve RNA sequences derived from the viral genome. The
      data show that alterations in the polymerase domain, in particular, mutations
      that are in positions that would be expected to alter the interaction of RT with
      the template-primer, can alter both the efficiency and specificity of RNase H
      cleavage. These results are discussed in light of the structure of HIV-1 RT.

PMID- 9533881
TI  - Microbial genome analyses: global comparisons of transport capabilities based on
      phylogenies, bioenergetics and substrate specificities.
AB  - We have conducted genome sequence analyses of seven prokaryotic microorganisms
      for which completely sequenced genomes are available (Escherichia coli,
      Haemophilus influenzae, Helicobacter pylori, Bacillus subtilis, Mycoplasma
      genitalium, Synechocystis PCC6803 and Methanococcus jannaschii). We report the
      distribution of encoded known and putative polytopic cytoplasmic membrane
      transport proteins within these genomes. Transport systems for each organism were
      classified according to (1) putative membrane topology, (2) protein family, (3)
      bioenergetics, and (4) substrate specificities. The overall transport
      capabilities of each organism were thereby estimated. Probable function was
      assigned to greater than 90% of the putative transport proteins identified. The
      results show the following: (1) Numbers of transport systems in eubacteria are
      approximately proportional to genome size and correspond to 9.7 to 10.8% of the
      total encoded genes except for H. pylori (5.4%), Synechocystis (4.7%) and M.
      jannaschii (3.5%) which exhibit substantially lower proportions. (2) The
      distribution of topological types is similar in all seven organisms. (3)
      Transport systems belonging to 67 families were identified within the genomes of
      these organisms, and about half of these families are also found in eukaryotes.
      (4) 12% of these families are found exclusively in Gram-negative bacteria, but
      none is found exclusively in Gram-positive bacteria, cyanobacteria or archaea.
      (5) Two superfamilies, the ATP-binding cassette (ABC) and major facilitator (MF)
      superfamilies account for nearly 50% of all transporters in each organism, but
      the relative representation of these two transporter types varies over a tenfold
      range, depending on the organism. (6) Secondary, pmf-dependent carriers are 1.5
      to threefold more prevalent than primary ATP-dependent carriers in E. coli, H.
      influenzae, H. pylori and B. subtilis while primary carriers are about twofold
      more prevalent in M. genitalium and Synechocystis. M. jannaschii exhibits a
      slight preference for secondary carriers. (7) Bioenergetics of transport
      generally correlate with the primary forms of energy generated via available
      metabolic pathways but ecological niche and substrate availability may also be
      determining factors. (8) All organisms display a similar range of transport
      specificities with quantitative differences presumably reflective of disparate
      ecological niches. (9) M. jannaschii and Synechocystis have a two to threefold
      increased proportion of transporters for inorganic ions with a concomitant
      decrease in transporters for organic compounds. (10) 6 to 18% of all transporters
      in these bacteria probably function as drug export systems showing that these
      systems are prevalent in non-pathogenic as well as pathogenic organisms. (11) All
      seven prokaryotes examined encode proteins homologous to known channel proteins,
      but none of the channel types identified occurs in all of these organisms. (12)
      The phosphoenolpyruvate:sugar phosphotransferase system is prevalent in the large
      genome organisms, E. coli and B. subtilis, and is present in the small genome
      organisms, H. influenzae and M. genitalium, but is totally lacking in H. pylori,
      Synechocystis and M. jannaschii. Details of the information summarized in this
      article are available on our web sites, and this information will be periodically
      updated and corrected as new sequence and biochemical data become available.

PMID- 9533882
TI  - Dehydration of biological membranes by cooling: an investigation on the purple
      membrane.
AB  - The lamellar spacing dl of purple membrane (PM) multilayer systems was
      investigated with neutron diffraction as a function of temperature and of the
      level of hydration. The observed large T-dependent variations of dl indicate that
      PM is partially dehydrated when cooled below a "hydration water freezing point".
      This phenomenon is reversible, but a hysteresis is observed when PM is rehydrated
      upon reheating. The hydration water remaining bound to the membrane below about
      240 K is non-freezing. Its amount was found to be hnf=0.24(+/-0.02) g 2H2O/g BR
      for all samples equilibrated at room temperature in the presence of 2H2O vapour
      at >/=84% r.h. It is evident, that the dehydration/rehydration behaviour of PM is
      strongly correlated with the temperature-dependent behaviour of the dynamical
      structure factor. Above the well-known "dynamical transition" announcing the
      onset of localized diffusive molecular motions between 190 K and 230 K, a second
      dynamical transition is caused by the temperature-induced rehydration of the PM
      starting near 255 K. This is also correlated with the deviation from a pure
      Arrhenius law of the rate-limiting process in the photocycle, known to occur upon
      cooling beyond the ice point into the same temperature region. Our results
      suggest that the phenomenon of dehydration and rehydration induced by cooling and
      reheating, respectively, is a general property of biological membranes.

PMID- 9533883
TI  - The solution structure of a fungal AREA protein-DNA complex: an alternative
      binding mode for the basic carboxyl tail of GATA factors.
AB  - The solution structure of a complex between the DNA binding domain of a fungal
      GATA factor and a 13 base-pair oligonucleotide containing its physiologically
      relevant CGATAG target sequence has been determined by multidimensional nuclear
      magnetic resonance spectroscopy. The AREA DNA binding domain, from Aspergillus
      nidulans, possesses a single Cys2-Cys2 zinc finger module and a basic C-terminal
      tail, which recognize the CGATAG element via an extensive network of hydrophobic
      interactions with the bases in the major groove and numerous non-specific
      contacts along the sugar-phosphate backbone. The zinc finger core of the AREA DNA
      binding domain has the same global fold as that of the C-terminal DNA binding
      domain of chicken GATA-1. In contrast to the complex with the DNA binding domain
      of GATA-1 in which the basic C-terminal tail wraps around the DNA and lies in the
      minor groove, the structure of complex with the AREA DNA binding domain reveals
      that the C-terminal tail of the fungal domain runs parallel with the sugar
      phosphate backbone along the edge of the minor groove. This difference is
      principally attributed to amino acid substitutions at two positions of the AREA
      DNA binding domain (Val55, Asn62) relative to that of GATA-1 (Gly55, Lys62). The
      impact of the different C-terminal tail binding modes on the affinity and
      specificity of GATA factors is discussed.

PMID- 9533885
TI  - Structural basis for molecular recognition between nuclear transport factor 2
      (NTF2) and the GDP-bound form of the Ras-family GTPase Ran.
AB  - Nuclear transport factor 2 (NTF2) and the Ras-family GTPase Ran are two soluble
      components of the nuclear protein import machinery. NTF2 binds GDP-Ran
      selectively and this interaction is important for efficient nuclear protein
      import in vivo. We have used X-ray crystallography to determine the structure of
      the macromolecular complex formed between GDP-Ran and nuclear transport factor 2
      (NTF2) at 2.5 A resolution. The interaction interface involves primarily the
      putative switch II loop of Ran (residues 65 to 78) and the hydrophobic cavity and
      surrounding surface of NTF2. The major contribution to the interaction made by
      the switch II loop accounts for the ability of NTF2 to discriminate between GDP
      and GTP-bound forms of Ran. The aromatic side-chain of Ran Phe72 inserts into the
      NTF2 cavity and accounts for 22% of the surface area buried by the interaction
      interface, while salt bridges are formed between Lys71 and Arg76 of Ran with
      Asp92/Asp94 and Glu42 of NTF2, respectively. These salt bridges account for the
      inhibition of the Ran-NTF2 interaction by NTF2 mutants such as E42 K and D92/94N
      in which the negatively charged residues surrounding the cavity were altered.
      Because the interaction interface maintains the positions of key Ran residues
      involved in binding MgGDP, NTF2 binding may help stabilize the switch state of
      Ran, possibly in the context of targeting it to other components of the nuclear
      protein import machinery to specify directionality of transport. The binding of
      GDP-Ran at the NTF2 cavity raises the possibility that this interaction might be
      modulated by a metabolite or small molecule substrate for NTF2's putative
      enzymatic activity.

PMID- 9533884
TI  - The solution structure of the Leu22-->Val mutant AREA DNA binding domain
      complexed with a TGATAG core element defines a role for hydrophobic packing in
      the determination of specificity.
AB  - The seemingly innocuous leucine-to-valine mutation at position 22 of the AREA DNA
      binding domain results in dramatic changes in the in vivo expression profile of
      genes controlled by this GATA transcription factor. This is associated with a
      preference of the Leu22-->Val mutant for TGATAG sites over (A/C)GATAG sites.
      Quantitative gel retardation assays confirm this observation and show that the
      Leu22-->Val mutant AREA DNA binding domain has a approximately 30-fold lower
      affinity than the wild-type domain for a 13 base-pair oligonucleotide containing
      the wild-type CGATAG target. To gain insight into the measured affinity data and
      further explore sequence specificity of the AREA protein, the solution structure
      of a complex between the Leu22-->Val mutant AREA DNA binding domain and a 13 base
      pair oligonucleotide containing its physiologically relevant TGATAG target
      sequence has been determined by multidimensional nuclear magnetic resonance
      spectroscopy. Comparison of this structure with that of the wild-type AREA DNA
      binding domain complexed to its cognate CGATAG target site shows how subtle
      changes in amino acid side-chain length and hydrophobic packing can affect
      affinity and specificity for GATA-containing sequences, and how changes in DNA
      sequence can be compensated for by changes in protein sequence.

PMID- 9533886
TI  - Kinetic and X-ray structural studies of three mutant E. coli alkaline
      phosphatases: insights into the catalytic mechanism without the nucleophile
      Ser102.
AB  - Escherichia coli alkaline phosphatase (EC 3.1.3.1) is a non-specific
      phosphomonoesterase that catalyzes the hydrolysis reaction via a phosphoseryl
      intermediate to produce inorganic phosphate and the corresponding alcohol. We
      investigated the nature of the primary nucleophile, fulfilled by the deprotonated
      Ser102, in the catalytic mechanism by mutating this residue to glycine, alanine
      and cysteine. The efficiencies of the S102G, S102A and S102C enzymes were 6 x
      10(5)-fold, 10(5)-fold and 10(4)-fold lower than the wild-type enzyme,
      respectively, as measured by the kcat/Km ratio, still substantially higher than
      the non-catalyzed reaction. In order to investigate the structural details of the
      altered active site, the enzymes were crystallized and their structures
      determined. The enzymes crystallized in a new crystal form corresponding to the
      space group P6322. Each structure has phosphate at each active site and shows
      little departure from the wild-type model. For the S102G and S102A enzymes, the
      phosphate occupies the same position as in the wild-type enzyme, while in the
      S102C enzyme it is displaced by 2.5 A. This kinetic and structural study suggests
      an explanation for differences in catalytic efficiency of the mutant enzymes and
      provides a means to study the nature and strength of different nucleophiles in
      the same environment. The analysis of these results provides insight into the
      mechanisms of other classes of phosphatases that do not utilize a serine
      nucleophile.

PMID- 9533887
TI  - Solution structure and dynamics of linked cell attachment modules of mouse
      fibronectin containing the RGD and synergy regions: comparison with the human
      fibronectin crystal structure.
AB  - We report the three-dimensional solution structure of the mouse fibronectin cell
      attachment domain consisting of the linked ninth and tenth type III modules,
      mFnFn3(9,10). Because the tenth module contains the RGD cell attachment sequence
      while the ninth contains the synergy region, mFnFn3(9,10) has the cell attachment
      activity of intact fibronectin. Essentially complete signal assignments and
      approximately 1800 distance and angle restraints were derived from
      multidimensional heteronuclear NMR spectra. These restraints were used with a
      hybrid distance geometry/simulated annealing protocol to generate an ensemble of
      20 NMR structures having no distance or angle violations greater than 0.3 A or 3
      degrees. Although the beta-sheet core domains of the individual modules are well
      ordered structures, having backbone atom rmsd values from the mean structure of
      0.51(+/-0.12) and 0.40(+/-0.07) A, respectively, the rmsd of the core atom
      coordinates increases to 3.63(+/-1.41) A when the core domains of both modules
      are used to align the coordinates. The latter result is a consequence of the fact
      that the relative orientation of the two modules is not highly constrained by the
      NMR restraints. Hence, while structures of the beta-sheet core domains of the NMR
      structures are very similar to the core domains of the crystal structure of
      hFnFn3(9,10), the ensemble of NMR structures suggests that the two modules form a
      less extended and more flexible structure than the fully extended rod-like
      crystal structure. The radius of gyration, Rg, of mFnFn3(9,10) derived from small
      angle neutron scattering measurements, 20.5(+/-0.5) A, agrees with the average Rg
      calculated for the NMR structures, 20.4 A, and is ca 1 A less than the value of
      Rg calculated for the X-ray structure. The values of the rotational anisotropy, D
      ||/D perpendicular, derived from an analysis of 15N relaxation data, range from
      1.7 to 2.1, and are significantly less than the anisotropy of 2.67 predicted by
      hydrodynamic modeling of the crystal coordinates. In contrast, hydrodynamic
      modeling of the NMR coordinates yields anisotropies in the range of 1.9 to 2.7
      (average 2.4(+/-0.2)), with NMR structures bent by more than 20 degrees relative
      the crystal structure having calculated anisotropies in best agreement with
      experiment. In addition, the relaxation parameters indicate that several loops in
      mFnFn3(9,10), including the RGD loop, are flexible on the nanosecond to
      picosecond time-scale. Taken together, our results suggest that, in solution, the
      limited set of interactions between the mFnFn3(9,10) modules position the RGD and
      synergy regions to interact specifically with cell surface integrins, and at the
      same time permit sufficient flexibility that allows mFnFn3(9,10) to adjust for
      some variation in integrin structure or environment.

PMID- 9533888
TI  - Determination of the structure of oxidised Desulfovibrio africanus ferredoxin I
      by 1H NMR spectroscopy and comparison of its solution structure with its crystal
      structure.
AB  - The solution structure of the 64 amino acid Fe4S4 ferredoxin I from Desulfovibrio
      africanus has been determined using two-dimensional 1H NMR spectroscopy. Sequence
      specific assignments were obtained for 59 amino acid residues and the structure
      determined with the program DIANA on the basis of 549 nuclear Overhauser
      enhancement (NOE) upper distance limits, and four dihedral angle and 52 distance
      constraints for the Fe4S4 cluster. The NMR structure was refined using the
      simulated annealing and energy minimisation protocols of the program X-PLOR to
      yield a final family of 19 structures selected on the basis of good covalent
      geometry and minimal restraint violations. The r.m.s.d. values to the average
      structure for this family are 0.49(+/-0.07) A and 0.94(+/-0.09) A for the
      backbone and heavy-atoms of residues 3 to 62, respectively. The NMR structure has
      been compared to the previously reported X-ray structures for the two molecules
      within the asymmetric unit of the crystal, which have a network of seven hydrogen
      bonds between them. This intermolecular interface, involving residues 38, 40 to
      43 and 46, has the same conformation in the solution structures showing that the
      crystal packing does not perturb the structure. There are three regions in which
      the NMR and X-ray structures differ: around the cluster, a turn involving
      residues 8 to 10, and a loop involving residues 29 to 32. In the family of
      solution structures the backbone of the loop region incorporating residues 29 to
      32 is well-defined whilst in both of the X-ray molecules it is ill-defined. The
      small differences between the X-ray and NMR structures for the cluster
      environment and the turn between residues 8 to 10 probably reflects a lack of NMR
      constraints. The observation of relatively rapid amide NH hydrogen exchange of NH
      groups close to the cluster, together with rapid flipping for Phe25, which is
      also close to the cluster, indicates that the cluster environment is more dynamic
      than the corresponding regions of related Fe/S proteins.

PMID- 9533889
TI  - Structural stability and internal motions of Escherichia coli ribonuclease HI:
      15N relaxation and hydrogen-deuterium exchange analyses.
AB  - The relationship between the structural stability and the internal motions of
      proteins was investigated through measurements of 15N relaxation and hydrogen
      deuterium exchange rates of ribonuclease HI from Escherichia coli and its
      thermostable quintuple mutant (Gly23-->Ala, His62-->Pro, Val74-->Leu, Lys95-
      >Gly, and Asp134-->His), which has a higher melting temperature by 20.2 degreesC.
      For most of the residues, the generalized order parameters (S2) obtained from 15N
      relaxation analyses as well as the localized hydrogen-bond-breaking motions
      (local breathing) observed as fast H-D exchange rates were largely unaffected by
      the mutations, indicating no global mutational effect on the internal motions.
      Several local mutational effects were observed for residues close to the mutation
      sites as follows. The S2 value significantly increased for Lys96 and Val98, which
      indicated that motions on the pico- to nanosecond time-scale became restricted
      within a protruding region including the Lys95-->Gly mutation site. In contrast,
      slight decreases in S2, and drastic increases in the chemical exchange motion on
      the micro- to millisecond time-scale (Deltaex), were observed for residues
      located in the joining region between the protrusion and the major domain of the
      protein. These changes may be caused by the elimination of the bulky Lys95 side
      chain at the center of the protrusion. Deltaex observed for residues in alpha
      helix I of the wild-type protein was reduced for the mutant, probably because a
      cavity in the hydrophobic core is filled by the Val74-->Leu mutation. The local
      breathing at position 134 was restricted by the Asp134-->His mutation, probably
      because the reduction of the negative charge repulsion contributes to the
      stability of the native major conformation relative to the breathing
      conformations around position 134.

PMID- 9533890
TI  - Recognition of protein substrates by the prolyl isomerase trigger factor is
      independent of proline residues.
AB  - The trigger factor is associated with bacterial ribosomes and catalyzes proline
      limited protein folding reactions. Its folding activity is very high and
      conserved in evolution, as shown for the homologous enzymes from Escherichia coli
      and Mycoplasma genitalium. The folding protein substrate (a variant of
      ribonuclease T1) binds with high affinity to the trigger factors, and permanently
      unfolded proteins are strong, competitive inhibitors. We used this inhibition to
      characterize the substrate binding sites of the trigger factors. Unfolded alpha
      lactalbumin binds very tightly and inhibits the trigger factor from M. genitalium
      with a KI value of 50 nM. The binding of inhibitory proteins is independent of
      proline residues, as shown for unfolded tendamistat, which binds to the trigger
      factor with equal affinity in the presence and in the absence of its three
      proline residues. The good inhibition by a non-folding variant of ribonuclease T1
      that lacks Pro39 showed that this proline, at which the catalysis of folding
      occurs, is dispensable for substrate binding. The trigger factors cannot catalyze
      prolyl isomerization when proteins are partially folded already. They
      preferentially recognize unstructured protein chains, which bind with high
      affinity to a site distinct from the catalytic prolyl isomerase center in the
      FKBP domain.

PMID- 9533891
TI  - Refolding kinetics of staphylococcal nuclease and its mutants in the presence of
      the chaperonin GroEL.
AB  - We have analyzed the effect of the chaperonin GroEL on the refolding kinetics of
      staphylococcal nuclease and its three mutants by stopped-flow fluorescence
      measurements. It was found that a transient folding intermediate of
      staphylococcal nuclease was tightly bound to GroEL and refolded in the GroEL
      bound state without releasing the non-native protein in solution, and the
      refolding rate in the GroEL-bound state was 0.01 s-1. The GroEL-affected
      refolding of the nuclease appears to be in decided contrast to that of apo-alpha
      lactalbumin reported in our previous study, wherein alpha-lactalbumin was shown
      to be more weakly bound by GroEL and to refold in the free state in solution. In
      spite of the apparent difference between the proteins, the GroEL-affected
      refolding reactions of both the proteins can be represented by a common unified
      reaction scheme. On the basis of this scheme, the binding constant between the
      nuclease intermediate and GroEL was estimated to be larger than 10(9) M-1. The
      stoichiometry of binding of the nuclease and its mutants to GroEL was found to be
      two (nuclease/GroEL 14-mer). The increase in ionic strength resulted in a
      weakening of the interaction between the nuclease and GroEL, which was attributed
      to a weakening of the electrostatic attraction between the two proteins as a
      result of electrostatic screening by ions. Although ATP was found to accelerate
      the GroEL-affected refolding of the nuclease, the refolding rate was still far
      from the rate of the free refolding. The free refolding behavior of the nuclease
      and its mutants was restored in the presence of the cochaperonin GroES and ATP.

PMID- 9533892
TI  - Transposon Tn916 insertional mutagenesis of Pasteurella multocida and direct
      sequencing of disruption site.
AB  - The transposon Tn916, when introduced into Pasteurella multocida by
      electroporation on a nonreplicating plasmid, integrates into the bacterial
      chromosome. Efficiencies of approximately 8x10(4) mutants/microg of plasmid DNA
      were obtained. Restriction digestion and Southern analysis indicate that the
      Tn916 element integrates in a quasi-random fashion throughout the genome. Most
      transformants had a single copy of the transposon but approximately 5% had two
      copies. Furthermore, the nucleotide sequence at the disruption site of any
      desired mutant was obtained by capitalizing on the differential sensitivity of
      the transposon and the genome to the restriction enzyme HhaI; molecular cloning
      or amplification by polymerase chain reaction was not required. The Tn916 element
      has a single HhaI site. On the other hand, this restriction enzyme frequently
      cleaves the P. multocida chromosome with the vast majority of the resulting
      genomic fragments being less than 7 kb in length. Tn916 integration adds a 12 kb
      segment to the genomic HhaI fragment at the site of disruption. The resulting
      chimeric DNA fragment was isolated on the basis of size from digests of mutant
      genomic DNA separated on agarose gels. DNA sequencing with primers corresponding
      to the terminus of the Tn916 element was used to determine the sequence at the
      disruption site. In summary, Tn916 can be used to disrupt and to clone genes of
      P. multocida in a rapid and facile fashion.

PMID- 9533893
TI  - Characterization of the haemolytic activity of Streptococcus equi.
AB  - The haemolytic activity of Streptococcus equi, the cause of equine strangles, was
      characterized. Production of haemolysin in Todd Hewitt broth was dependent on an
      equine serum supplement and the logarithmic phase of growth after which activity
      declined sharply. RNA core also induced haemolysin production from cells
      harvested at the end of the logarithmic phase of growth. Haemolysis was not
      affected by cholesterol, was only slightly increased in reducing conditions and
      was completely inactivated by trypan blue, identifying the haemolytic activity as
      streptolysin S-like (SLS-like). Purification by hydroxyapatite and Sephacryl
      column chromatography yielded proteins of molecular weights of approximately 6000
      and 17 000-22 000 Da with a 64-fold increase in specific activity. Low molecular
      weight proteins from the RNA core were still present in the purified toxin. Two
      non-haemolytic mutants were derived by conjugation with an Enterococcus faecalis
      carrying transposon Tn916. Southern blots of HindIII digests of DNA revealed that
      one of the mutants contained three transposon insertions and the other just one.
      A lambda phage library of S. equi contained plaques whose haemolytic activity was
      enhanced by reducing conditions and inhibited by cholesterol, suggesting a
      streptolysin O-like (SLO-like) activity. However, haemolysin in culture sonicates
      of host E. coli in which the lambda phage insert was subcloned into plasmid
      (pUC18), was not affected by these conditions. Seven isolates of S. equi in
      medium without SLS-like inducers showed no SLO-like activity and no evidence for
      an SLO-like toxin could be found by immunoblotting with pneumolysin antiserum and
      monoclonal antibodies or by polymerase chain reaction with primers derived from
      sequences conserved between the SLO genes of Lancefield group A, C and G
      streptococci. S. equi does not appear to possess a streptolysin O but does make a
      streptolysin S-like toxin whose production can be interrupted at just one genetic
      locus.

PMID- 9533894
TI  - Molecular analysis of the gene encoding the immunodominant phenotypically varying
      P270 protein of Trichomonas vaginalis.
AB  - Trichomonas vaginalisis a flagellated protozoan responsible for the most common
      non-viral sexually transmitted disease. The immunogen P270 was previously found
      to be up-regulated in expression and to undergo phenotypic variation between
      surface versus cytoplasmic localization in trichoImonads harbouring a dsRNA
      virus. In this report, we characterize the entire p270 open reading frame (ORF)
      and the unknown flanking 5;- and 3;-unique, non-repeat coding sequences of the
      gene in addition to untranslated regions. Consistent with an earlier report
      (Dailey & Alderete, 1991, Infect. Immun. 59: 2083-88), a significant portion of
      the gene consists of a tandemly repeated 333 bp element that contains the
      sequence coding for the epitope DREGRD detected by murine monoclonal antibody and
      antibody from the sera of patients. The non-repeat coding regions for the 5;- and
      3;-ends were 69 nucleotides (23 amino acids) and 1183 nucleotides (395 amino
      acids), respectively. Sequencing of repeat elements showed them to be identical,
      affirming the highly-conserved nature of this element throughout the gene. The
      start codon was immediately preceded by the 12 nucleotide consensus sequence
      (TCATTTTTAATA) found in other trichomonad protein-coding genes. A very AT-rich,
      non-coding region was identified upstream of the p270 ORF. P270 appears to
      contain a leader sequence at the amino-terminus and transmembrane domain at the
      carboxy-terminus. No significant homology was found with any reported proteins at
      either the nucleotide or amino acid level.

PMID- 9533895
TI  - Assessment of the role of gamma-toxin in experimental endophthalmitis using a hlg
      deficient mutant of Staphylococcus aureus.
AB  - Purified gamma-toxin is known to have a proinflammatory effect in the rabbit
      vitreous humor. To assess the biological role of the gamma-toxin, when expressed
      in vivo by Staphylococcus aureus strain Newman, the vitreous humor of rabbit eye
      was used as an infection model. A gamma-toxin-deficient mutant of strain Newman
      was constructed by allelic replacement. S. aureus Newman wild-type, its hlg
      deficient derivative strain (N65) and the strain N65 complemented with the wild
      type hlg+ gene were injected into the vitreous humor of rabbit eye. All three
      strains produced a strong proinflammatory effect in the eye conjunctiva,
      posterior and anterior chambers, suggesting a role for another unidentified
      proinflammatory component of strain Newman distinct from the gamma-toxin. These
      components are not the leucocidin of Panton-Valentine, beta-toxin or alpha-toxin
      which are not produced by this strain. Only the hlg-deficient mutant lacked the
      ability to cause inflammation in the eyelid, whereas the two Hlg-producing
      strains gave strong inflammation. These data suggest that in vivo, strain Newman
      produces as yet unidentified proinflammatory molecules and that the in vivo
      produced HlgA, HlgB and HlgC molecules expressed by the gamma-toxin locus,
      contribute in part to the inflammatory process observed in vivo in the rabbit
      eye.

PMID- 9533896
TI  - Sulfated polysaccharides block chlamydia infection in vitro, but do not protect
      mice from vaginal inoculation.
AB  - There is considerable interest in developing a vaginal product that women could
      use to protect themselves from sexually transmitted pathogens, including
      chlamydia. It has been suggested that sulfated polysaccharides would be effective
      in a prophylactic product because they have been shown to block infection of
      cultured cells by sexually transmitted pathogens, including chlamydia. In order
      to compare in vitro findings with animals, we placed sulfated polysaccharides
      into the vaginae of mice prior to inoculation with chlamydia. The surfactant
      nonoxynol 9 (N9) was used as a positive control as it has been previously shown
      to protect mice from infection by chlamydia. In this study, N9 also protected the
      mice from infection. However, sulfated polysaccharides which had been shown to be
      efficacious in vitro did not block infection.

PMID- 9533897
TI  - Human pathogenic Mycoplasma species induced cytokine gene expression in Epstein
      Barr virus (EBV)-positive lymphoblastoid cell lines.
AB  - We addressed the question whether the in vitro interaction of two Epstein-Barr
      virus (EBV)-genome-positive B cell lines (EB-3 and HilB-gamma) with either
      Mycoplasma pneumoniae or M. hominis, with the <<AIDS-related>> mycoplasma species
      (M. fermentans, M. fermentans subsp. incognitus, M. penetrans, M. genitalium) or
      with mycoplasma species known to be mere commensals of the respiratory tract (M.
      orale and M. salivarium) would result in expression of mRNAs for IL-2, IL-2R, IL
      4 and IL-6 as determined by reverse transcriptase (RT)-PCR after 4 and 24 h of
      cocultivation. The pattern of cytokine gene expression observed depended on (i)
      the origin of the transformed cell line, (ii) the pathogenicity of the Mycoplasma
      species, and (iii) the length of cocultivation. The EBV-immortalized
      lymphoblastoid cell line HilB-gamma showed mRNA expression for IL-2, IL-2
      receptor, IL-4 and IL-6 peaking 24 h after stimulation with M. pneumoniae and all
      AIDS-related mycoplasma species tested. The Burkitt lymphoma cell line EB-3
      showed a distinct and isolated strong II-2/IL-2 R-mRNA expression within 4 h
      after contact with the pathogenic and all of the AIDS related mycoplasma species.
      In neither EBV-containing cell line cytokine was gene expression detectable after
      stimulation with the commensal mycoplasma species, M. orale and M. salivarium,
      indicating species differences in the ability of mycoplasmas to interact with and
      stimulate B-cell lines. Our data suggest that some mcyoplasma species may act as
      immunomodulatory cofactors by eliciting inappropriate cytokine gene expression in
      B cells latently infected with EBV. Therefore, this cultivation model may prove
      useful in evaluating the pathogenetic potential of novel isolated mycoplasma
      species.

PMID- 9533898
TI  - Primary Campylobacter jejuni infection in different mice strains.
AB  - Campylobacter jejuni is one of the most frequent causes of diarrhoea in man.
      Extra-intestinal manifestations may also occur, particularly in immunocompromised
      individuals. However, because of the lack of appropriate animal models the
      pathophysiology and immunological response of the host to C. jejuni infection are
      still poorly understood. In our laboratory an experimental infection of adult
      BALB/c, C57BL/6 and DBA/2 mice has been established. After intraperitoneal
      injection of 0.5-1x10(9) cfu of C. jejuni none of the infected mice showed
      clinical symptoms of illness, but bacterial spreading and tissue invasion were
      achieved. We have concentrated our studies on the duration of primary infection,
      recovery of bacteria from livers and spleens of infected animals and
      pathohistological changes of these organs. Our results showed differences in the
      course of systemic infection among the tested mice strains. BALB/c mice were most
      sensitive, resulting in the most pronounced pathohistological changes in the
      examined organs. The duration of the primary liver infection was the longest in
      BALB/c mice while the duration of the splenic infection also differed among the
      tested mice strains. Nevertheless, the experimental model used in this study can
      be efficiently used in further analysis of the pathogenesis of this bacterial
      infection. However, the strain differences should be taken into account depending
      on the parameters to be followed.

PMID- 9533899
TI  - Quadrupole-dipole effects in solid-state, CP-MAS, tin-119 NMR spectra of para
      substituted Triaryltin(pentacarbonyl)manganese(I) complexes 
AB  - Solid-state, CP-MAS, 119Sn NMR spectra were measured for a series of para
      substituted triaryltin(pentacarbonyl)manganese(I) complexes. All the spectra show
      an asymmetric sextet due to spin-spin coupling and second-order quadrupolar
      effects, transmitted by dipolar coupling between the 119Sn and 55Mn nuclei, which
      are not suppressed by magic-angle rotation. The solid-state 1JMn-Sn spin-spin and
      nuclear quadrupole coupling constants range from 130 to 250 Hz and -8 to 21 MHz,
      respectively, and show an inverse linear correlation, which is attributed to the
      dominance of the Fermi contact contribution to the 1JMn-Sn coupling. The tris(p
      methylthiophenyl)tin derivative is an exception, attributed to a difference in
      crystal structure from the other complexes. The magnitudes of the principal
      elements of the 119Sn chemical shift tensors were determined and appear to be
      strongly influenced by the ring torsion angles and the para-substituents of the
      phenyl rings. Solid-state 119Sn NMR spectroscopy provides a useful method of
      probing the electronic environment around the tin and manganese nuclei in
      transition metal complexes. Copyright 1998 Academic Press.

PMID- 9533901
TI  - Optically detected electron spin echo envelope modulation on a photoexcited
      triplet state in zero magnetic field-A comparison between the zero-field and high
      field limits 
AB  - Electron spin echo envelope modulation (ESEEM) has been studied at zero and low
      magnetic fields (B </= 100 G) by means of optically detected magnetic resonance.
      Qualitative differences of the ESEEM effect for an electronic triplet state (S =
      1) under low-field and high-field conditions are observed and discussed. They are
      related to the different properties of the total spin angular momentum operator S
      and the hyperfine interaction at zero and high magnetic field. The novel method
      was applied to the photoexcited triplet state of acridine-d9 in a fluorene-h10
      matrix. An analysis of the observed nitrogen quadrupole splitting is done by a
      quantitative description of the ESEEM effect in zero field. Copyright 1998
      Academic Press.

PMID- 9533900
TI  - Effects of Sandimmune neoral on collagen-induced arthritis in DA rats:
      characterization by high resolution three-dimensional magnetic resonance imaging
      and by histology.
AB  - In the present work the time course of collagen-induced arthritis and the effect
      of Sandimmune Neoral in this model of arthritis were followed in the rat over an
      extended period of time (70 days) using high resolution three-dimensional (3D)
      magnetic resonance imaging (MRI). High resolution 3D gradient-echo (TR = 100 ms;
      TE = 3.8 ms) images with a voxel size of 94 x 81 x 60 micron3 were acquired from
      the hind paw of DA rats (n = 21) at various time points after injection of type
      II bovine collagen into the tail. Eleven rats were treated with Neoral (15
      mg/kg/day p.o. together with vehicle) for 42 days starting at day 14 after
      collagen injection. The remaining controls received vehicle. Pathomorphological
      changes associated with the collagen-induced arthritic process, e.g., increase of
      joint space and cartilage and bone erosion, could be observed in vivo in the
      control group. In contrast, no changes in the joint architecture were detected in
      Neoral-treated animals. Indeed, Neoral showed strong anti-inflammatory effects
      and marked protection against cartilage and bone destruction in this model.
      Qualitative information derived from the MR images correlated significantly with
      histological findings.

PMID- 9533902
TI  - Multiecho imaging with suboptimal spoiler gradients.
AB  - Although multiecho imaging may be used to measure transverse relaxation (T2), B1
      and B0 inhomogeneity generally gives rise to unwanted coherence pathway signals
      which result in erroneous T2 measurements. One approach to suppressing this
      unwanted signal is to center each rf refocusing pulse between spoiler gradients
      which dephase the unwanted signal; however, hardware limitations often dictate
      the use of suboptimal spoiler gradients, that is, gradients that cannot provide
      sufficient dephasing strength. Using simulations, this work demonstrates that by
      means of a small additional spoiler gradient prior to the first rf refocusing
      pulse it is possible to reduce substantially the contribution from unwanted
      coherence pathways in multiecho imaging studies that use suboptimal spoiler
      gradients. This reduction of unwanted signal results in measured T2 values within
      approximately 1% of values obtained using spoiler gradients of optimal strength.
      These results were found for a wide range of biologically relevant T1 and T2
      values, missettings of the rf refocusing pulse as large as 5%, and frequency
      offsets of up to 25 Hz. Multiecho image data agreed with the simulations. Using
      the additional spoiler gradient it is possible to reduce spoiler gradient
      strengths by up to 75%.

PMID- 9533903
TI  - A birdcage coil tuned by RF shielding for application at 9.4 T.
AB  - The design and performance of an inductively fed low-pass birdcage radiofrequency
      (RF) coil for applications at 9.4 T are described where tuning is accomplished by
      mechanically moving a concentric RF shield about the longitudinal axis of an RF
      coil. Moving the shield about the RF coil effectively changes the mutual
      inductance of the system, providing a mechanism for adjusting the resonant
      frequency. RF shield tuning eliminates adjustable capacitors on the legs of the
      RF coil, eliminates current imbalances and field distortions, and results in
      improved B1 field homogeneity and high quality (Q) factors. RF shield tuning and
      inductive matching provide an isolated resonance structure which is both
      physically and electrically unattached. Experimental analysis of shield position
      on both B1 field homogeneity and resonant frequency is provided. Computer
      simulations of B1 field homogeneity as a function of shield position and shield
      diameter are also presented. Magnetic resonance microimaging substantiates the
      usefulness of this design.

PMID- 9533904
TI  - Pulsed ENDOR studies at 95 GHz of the triplet state of 13C60 
AB  - Fully 13C-enriched C60 has been investigated by pulsed electron-nuclear double
      resonance (ENDOR) spectroscopy at W-band frequency at 1.2 K. For molecular C60
      the ENDOR spectra reflect the distortion of the molecule upon triplet excitation,
      and the fine-structure parameter D is found to be negative. For a single crystal
      of C60 the ENDOR spectra characterize the triplet excitation as delocalized over
      a pair of neighboring C60 molecules. Copyright 1998 Academic Press.

PMID- 9533906
TI  - A study of solvent polarity and hydrogen bonding effects on the nitrogen NMR
      shielding of isomeric tetrazoles and ab initio calculation of the nitrogen
      shielding of azole systems 
AB  - High-precision nitrogen NMR shieldings, bulk susceptibility corrected, are
      reported for the N-methyl derivatives of the two existing isomeric tetrazoles (I,
      II) in a variety of solvents which represent a wide range of solvent properties
      from the point of view of polarity as well as hydrogen bond donor and acceptor
      strength. The observed range of solvent-induced nitrogen shielding variations of
      I and II is significant for the pyrrole-type nitrogens (N-Me), up to 9 ppm, and
      even more so for pyridine-type nitrogen atoms, where it can attain a value of 20
      ppm. There is a clear distinction between the two types of nitrogen atoms in that
      the former exhibit a deshielding effect with increasing polarity of the medium
      while the latter experience an increase in the magnetic shielding of their
      nuclei. The latter effect is significantly augmented by solvent-to-solute
      hydrogen-bond formation where the pyridine-type nitrogens are involved directly.
      It is also quite diversified throughout the pyridine-type nitrogen atoms and
      seems to constitute a measure of relative basicity with respect to hydrogen-bond
      formation of the nitrogens concerned. This basicity seems to parallel that with
      respect to a full transfer of a proton, as can be reckoned from ab initio
      calculations of the relevant protonation energies reported in the present study.
      The experimental data for the tetrazoles in cyclohexane solutions are combined
      with those obtained in our earlier extensive studies on azole, diazole, and
      triazole ring systems, for a comparison with ab initio calculations of the
      nitrogen shieldings concerned. The latter were carried out using the coupled
      Hartree-Fock/GIAO/6-31++G** approach and geometry optimizations employing the
      same basis set; they show a good linear correlation with the experimental data
      and reproduce not only major changes but also most of the subtle variations in
      the experimental nitrogen shieldings of the azole systems as a whole. Copyright
      1998 Academic Press.

PMID- 9533905
TI  - Offset-dependent partial saturation in binomial solvent suppression sequences.
AB  - In vivo spectroscopic experiments are commonly done under partially T1 saturated
      conditions and saturation factors (observed signal intensity divided by fully
      relaxed intensity) used for quantitative analysis of absolute and relative
      metabolite concentrations. The conventional calculation of the saturation factor
      assumes uniform excitation across the spectrum. This assumption is violated when
      selective-excitation solvent peak suppression techniques, such as binomial
      sequences, are used. In this case, the degree of partial saturation, and hence
      the saturation factor, is dependent on the resonance offset. This has
      implications for the frequency offset of maximum excitation, solvent suppression
      effectiveness, absolute and relative quantitative measurements, and progressive
      saturation T1 measurements. In this paper, the jump and return (JR) and jump and
      return echo (JRE) sequences are examined in detail with regard to these
      implications. It is shown that offset-dependent partial saturation depends on the
      sequence used and can become significant. A saturation factor which is a function
      of offset can be used to correct for this effect and allow for proper
      quantitative interpretation of experimental results under partially saturated
      conditions.

PMID- 9533907
TI  - Measurement of R'2 in the presence of multiple spectral components using
      reference spectrum deconvolution.
AB  - A method is described for measuring R'2, the RF reversible contribution to the
      effective transverse relaxation rate in yellow trabecular marrow, as a means to
      evaluate trabecular bone structure and density. The method exploits the
      similarity in spectral composition of the marrow and fat in subcutaneous tissue.
      Under these conditions the gradient echo envelope of the marrow signal can be
      regarded as a convolution of a function describing the bone marrow intravoxel
      line broadening (R'2) with a function expressing chemical shift modulation, which
      is obtained from the echo envelope of the subcutaneous fat signal in a reference
      region. Simple division of each of a series of echoes by the reference signal is
      shown to afford a smooth decay which can be fitted to a model to extract R'2. The
      method has been evaluated in the upper femur of test subjects and a strong
      correlation of the thus derived R'2 values with those obtained by the GESFIDE
      technique is demonstrated. The close correspondence in spectral composition of
      proximal femur marrow and subcutaneous fat is further illustrated by means of
      localized spectroscopy. The major potential error source is global inhomogeneity
      in the reference region which can lead to an underestimation of the demodulation
      derived R'2.

PMID- 9533908
TI  - Non-mono-exponential attenuation of water and N-acetyl aspartate signals due to
      diffusion in brain tissue.
AB  - Diffusion measurements were performed on water and N-acetyl aspartate (NAA)
      molecules in excised brain tissue using a wide range of b-values (up to 28.3 x
      10(6) and 35.8 x 10(6) s cm-2 for water and NAA, respectively). The attenuation
      of the signals of water and NAA due to diffusion was measured at fixed diffusion
      times (tD). These measurements, in which the echo time (TE) was set to 70 ms,
      were repeated for several diffusion times ranging from 35 to 305 ms. Signal
      attenuations were fitted to mono-, bi-, and triexponential functions to obtain
      the apparent diffusion coefficients (ADCs) of these molecules at each diffusion
      time. From these experiments the following observations and conclusions were
      made: (1) Signal attenuation of water and NAA due to diffusion over the entire
      range of b values examined is not monoexponential and the extracted ADCs depend
      on the diffusion time; (2) In the case of water the experimental data are best
      fitted by a triexponential function, while for b values up to 1 x 10(6) s cm-2, a
      biexponential function seems to reproduce the experimental data as well as the
      triexponential function; (3) If only the low range of b values are fitted (up to
      0.5 x 10(6) s cm-2) signal attenuation of water is monoexponential and
      insensitive to tD; (4) Water ADCs decreased with the increase in tD but the
      relative population of the fast diffusing component increases such that at a tD
      of 305 ms there is nearly a single population; (5) The major fast diffusion
      component of the water shows only very limited restriction; (6) NAA signal
      attenuation is biexponential and analysis of the low b-value range gives only
      monoexponential decay, but the obtained ADC is sensitive to the diffusion time;
      (7) The ADCs obtained from fitting the data with a biexponential function
      decrease as diffusion time increases; (8) The relative population of the slow
      diffusing component decreases with increasing tD; (9) Both the fast and the slow
      diffusing components of NAA show a considerable restriction by what seems to be a
      nonpermeable barrier from which two compartments, one of 7-8 micron and one of
      approximately 1 micron, were calculated using the Einstein equation. It is
      suggested that the two compartments represent the NAA in cell bodies and in the
      intra-axonal space. The effect of the range of the b value used in the diffusion
      experiments on the results is discussed and used to reconcile some of the
      apparent discrepancies obtained in different experiments concerning water
      diffusion in brain tissue. The potential of NAA diffusion experiments to probe
      cellular structure is discussed.

PMID- 9533909
TI  - Measurement of the longitudinal relaxation time by continuous-wave, nonlinear
      electron spin resonance spectroscopies 
AB  - We characterize a continuous-wave, nonlinear electron spin resonance spectroscopy
      which detects the longitudinal component of the magnetization. It is demonstrated
      that the signal is proportional to the Laplace transform of a relaxation function
      with decay time equal to the longitudinal relaxation time T1. The conclusion is
      reached by comparing T1 to the effective time T(eff)1 being drawn by progressive
      saturation for a nitroxide radical dissolved in supercooled o-terphenyl.
      Copyright 1998 Academic Press.

PMID- 9533910
TI  - Quantification of the contribution of extracellular sodium to 23Na multiple
      quantum-filtered NMR spectra of suspensions of human red blood cells.
AB  - 23Na double-quantum-filtered (DQF) NMR enables the detection of anisotropic
      motion of sodium ions due to their interaction with ordered structures in
      biological tissues. Using the technique, anisotropic motion was found for sodium
      ions in mammalian red blood cell suspensions (RBC) and the effect was shown to
      correlate with the integrity of membrane cytoskeleton. In the present study
      relative contributions to the DQF and triple-quantum-filtered (TQF) spectra of
      sodium bound to anisotropic and isotropic binding sites in the intra- and
      extracellular sodium pools (Na content being 15 and 150 mM, respectively) of
      human RBC were quantified for different hematocrits. DQF spectra were measured by
      a modified Jeener-Broekaert pulse sequence which enabled exclusive detection of
      anisotropically moving sodium ions. The relative contributions of the
      extracellular sodium to the TQF and DQF spectra decreased as the hematocrit
      increased, but their efficiency relative to the sodium content increased. The
      contribution of the extracellular sodium to the TQF signal was found to dominate
      the spectrum of the RBC suspension at all hematocrits studied. The contribution
      of the extracellular sodium to the DQF was significantly smaller than that to the
      TQF and was only 22% at a high hematocrit of about 90%.

PMID- 9533912
TI  - Generalized reciprocity.
AB  - The remarkable theorem of reciprocity as described by D. I. Hoult and R. E.
      Richards (J. Magn. Reson. 24, 71 (1976)) may be generalized to account for the
      near, intermediate, and radiation zone fields of a magnetic dipole. This form of
      reciprocity may be important when the wavelength of the NMR signal is not large
      compared to the distance scale of the system. In these situations the effects of
      interference may be significant. In addition, both the frequency dependence and
      distance dependence of the NMR signal amplitude are altered. In general, the
      distance dependence of the signal follows a weighted sum of 1/r3, 1/r2, and 1/r
      dependence. The frequency dependence of the signal amplitude is a function of
      omega, omega2, and omega3. Finally, the signal reflects the full vector field
      nature of the magnetic dipole. The mathematical expression of generalized
      reciprocity is completely equivalent to that of Hoult and Richards if the
      appropriate retarded potential form of the magnetic field is utilized.

PMID- 9533911
TI  - Determination of high-spin iron(III)-nitroxyl distances in spin-labeled
      porphyrins by time-domain EPR.
AB  - Continuous wave EPR spectra of the nitroxyl signals for four spin-labeled high
      spin (h.s.) Fe(III) porphyrins showed partially resolved splittings at
      temperatures near 4 K. Axial ligands were fluoride, chloride, or bromide. As
      temperature was increased to 20 to 30 K the iron-nitroxyl splitting collapsed due
      to increasing rates of iron relaxation. Electron spin-echo (ESE) spectroscopy
      showed that above about 6 K collapse of the iron-nitroxyl spin-spin splitting
      caused a dramatic increase in the nitroxyl phase memory relaxation rates.
      Electron spin relaxation rates were determined for Fe(tetratolylporphyrin)X, X =
      F, Cl, Br, in toluene solution by ESE or inversion recovery at 4.5 to 6 K and by
      analysis of the temperature-dependent contributions to the continuous wave EPR
      linewidths between about 10 and 120 K. Above about 10 K iron relaxation rates
      increase in the order X = F < Cl < Br, which is the order of increasing zero
      field splitting. Saturation recovery data for two spin-labeled h.s. iron(III)
      porphyrins between about 15 and 120 K and for two additional spin-labeled h.s.
      iron(III) porphyrins between about 85 and 120 K demonstrated that interaction
      with the h. s. iron enhanced the electron spin relaxation rate of the spin label.
      The saturation recovery curves for the nitroxyl were analyzed to determine
      interspin distances using a modified version of the Bloembergen equation and
      independently determined iron relaxation rates. Interspin distances were between
      11.6 and 15.0 A, were independent of axial ligand, and were in good agreement
      with values obtained previously for low-spin Fe(III) and Cu(II) analogs.

PMID- 9533913
TI  - Flip angle effects in STEAM and PRESS-optimized versus sinc RF pulses.
AB  - Flip angle dependence of the localized single-voxel 1H NMR spectroscopic
      sequences STEAM and PRESS using numerically optimized Shinnar-Le Roux (SLR) and
      conventional sinc RF pulses has been evaluated. Phantom experiments were used to
      evaluate voxel profiles from MR images of the selected voxels. Information on the
      total excited volume was recorded from the integrated area under the water peak
      in the localized spectrum at different flip angles (theta = 0 degrees-180
      degrees). The voxel profiles for both the STEAM and PRESS sequences using the SLR
      RF pulses were found to be identical, unlike the case for the sinc RF pulses. The
      SLR RF pulses in the PRESS sequence were found to be more sensitive to flip angle
      variations. Localized, water-suppressed 1H NMR spectra recorded from the frontal
      gray matter in healthy volunteers (n = 3) showed less lipid contamination using
      the SLR RF pulses compared with the sinc RF pulses.

PMID- 9533914
TI  - Temperature imaging by 1H NMR and suppression of convection in NMR probes 
AB  - A simple arrangement for suppressing convection in NMR probes is tested
      experimentally. Diffusion experiments are used to determine the onset of
      convection and 1H temperature imaging helps to rationalize the somewhat
      surprising results. A convenient new 1H NMR thermometer, CH2Br2 dissolved in a
      nematic thermotropic liquid crystal, is presented. Copyright 1998 Academic Press.

PMID- 9533915
TI  - A three-dimensional DOSY-HMQC experiment for the high-resolution analysis of
      complex mixtures 
AB  - A three-dimensional experiment is described in which NMR signals are separated
      according to their proton chemical shift, 13C chemical shift, and diffusion
      coefficient. The sequence is built up from a stimulated echo sequence with
      bipolar field gradient pulses and a conventional decoupled HMQC sequence. Results
      are presented for a model mixture of quinine, camphene, and geraniol in
      deuteriomethanol. Copyright 1998 Academic Press.

PMID- 9533916
TI  - Localized eddy current compensation using quantitative field mapping.
AB  - Eddy current effects induced by switched gradients in proximal conducting
      structures are traditionally reduced by applying preemphasis currents whose
      amplitudes and decay characteristics must be set to offset the eddy current
      fields. We present an expeditious, localized, and quantitative method for mapping
      and adjusting the parameters for eddy current compensation. Mapping is based on
      analysis of projections as used in the fast automatic shimming technique by
      mapping along projections (FASTMAP). Adjustment methods are demonstrated in high
      field horizontal bore systems. The proposed localized eddy current mapping
      technique may also be used for localized measurements in situations where
      asymmetric conducting structures may cause nonlinear eddy current fields, such as
      in interventional MRI and open magnet designs.

PMID- 9533917
TI  - QCPMG-MAS NMR of half-integer quadrupolar nuclei.
AB  - By combination of fast magic-angle spinning (MAS) and detection of the free
      induction decay during a rotor-synchronized quadrupolar Carr-Purcell-Meiboom-Gill
      (QCPMG) train of refocusing pulses, the sensitivity of quadrupolar-echo MAS NMR
      spectra for the central transition of half-integer quadrupolar nuclei exhibiting
      large quadrupolar couplings may be significantly enhanced. Enhancements by an
      order of magnitude may easily be realized while maintaining information about the
      anisotropic interactions. In the present study the so-called QCPMG-MAS experiment
      is demonstrated experimentally and by numerical simulations for the two 87Rb
      sites in Rb2SO4.

PMID- 9533918
TI  - Heteronuclear X-filter 1H PFG double-quantum experiments for the proton resonance
      assignment of a ligand bound to a protein.
AB  - A novel X-filter experiment based on 1H PFG DQ spectroscopy is described.
      Excellent suppression of proton bound to 13C and 15N is achieved. Successful
      application of the method to a protein-ligand complex is demonstrated.

PMID- 9533919
TI  - Noise-immune coil for unshielded magnetic resonance measurements 
AB  - A modified split-loop resonator that is electrically balanced and that has no
      magnetic dipole moment is shown to be relatively immune to environmental noise.
      Using a magnetic resonance surface coil of this design for 14N NQR at 3.4 MHz, it
      is demonstrated that magnetic resonance measurements can be made in the
      laboratory without additional RF shielding and with less than a 2 dB increase in
      the rms noise. Compared to more traditional designs, the modified split-loop
      resonator showed a net 17-dB gain in sensitivity for unshielded measurements.
      Copyright 1998 Academic Press.

PMID- 9533920
TI  - Direct structure refinement against residual dipolar couplings in the presence of
      rhombicity of unknown magnitude.
AB  - Residual dipolar couplings arising from small degrees of alignment of molecules
      in a magnetic field provide unique long-range structural information. The
      potential of this approach for structure refinement has recently been
      demonstrated for a protein-DNA complex in which the magnetic susceptibility
      tensor was axially symmetric. For most macromolecules and macromolecular
      complexes, however, axial symmetry cannot be assumed. Moreover, the presence of
      significant rhombicity will clearly affect the accuracy of the resulting
      coordinates. In this Communication we present a simple calculational strategy
      that makes use of simulated annealing refinement against the residual dipolar
      couplings in combination with a grid search, to simultaneously refine the
      structures and ascertain the magnitude of the axial and rhombic components of the
      tensor.

PMID- 9533922
TI  - A new method for measuring diffusion coefficients by 2D NMR using accordion
      spectroscopy 
AB  - Translational diffusion measurements are a useful tool for studying
      supramolecular complexes and for characterizing the association state of
      molecules that aggregate at NMR concentrations. Pulsed field gradients can be
      used to measure diffusion coefficients. Spectral overlap problems in complex
      mixtures can be alleviated by using 2D spectroscopy but the need to record a
      complete series of 2D spectra with increasing gradient strength makes these
      experiments extremely time consuming. Concerted incrementation of the gradient
      strength and the evolution time provides a new version of accordion spectroscopy
      that allows the measurement of individual diffusion coefficients in complex
      mixtures in a single experiment. Copyright 1998 Academic Press.

PMID- 9533921
TI  - The effects of atropisomerism and porphyrin deformation on 57Fe shieldings in
      superstructured hemoprotein models.
AB  - 57Fe NMR chemical shifts of superstructured heme model compounds have been found
      to be extremely sensitive to atropisomerism and deformation (ruffling) of the
      porphyrin geometry.

PMID- 9533923
TI  - The effect of RF power and spinning speed on MQMAS NMR 
AB  - It is known that the patterns of spinning sidebands observed in the multiple
      quantum dimension of MQMAS spectra are often significantly wider than expected
      from the anisotropies of relevant interactions. It has been recently shown by
      others that these sidebands are generated due to the rotor-driven reorientations
      that the quadrupole tensors of the crystallites undergo during the evolution
      period between the multiple- and single-quantum conversion processes. We present
      an experimental and theoretical study of the effects of the spinning speed nuR
      and RF field strength nuRF on the development of these sideband patterns. The
      theoretical analysis relies upon numerical simulations and includes propagation
      of the density matrix during the entire MQMAS experiment. The possibility of
      additional rotational encoding during the RF pulses is discussed. Both the
      theoretical and experimental results show the benefits of using the highest
      available nuR and nuRF. Copyright 1998 Academic Press.

PMID- 9533924
TI  - Meetings calendar 
AB  - Copyright

PMID- 9533925
TI  - Hybrid rendering of the cervico-cranial arteries using spiral computed
      tomography.
AB  - PURPOSE: The purpose of this study was to develop a shaded-surface and volume
      display (hybrid rendering method) of the whole vascular system of the cervico
      cranial arteries using spiral computed tomography (SCT). MATERIALS AND METHODS:
      We examined 12 patients with anatomic abnormalities and pathological conditions
      of the arterial vascular system. The cervico-cranial arteries were segmented
      using an interactive threshold interval density volume-growing method and
      visualized with a color-coded shaded-surface display (SSD) rendering method. The
      adjacent bone structures were visualized using a transparent volume rendering
      method. RESULTS: In all cases, the entire volume of the vascular system of the
      cervico-cranial arteries and the anatomic abnormalities and pathological
      conditions could be visualized. CONCLUSION: Hybrid rendering of the circulation
      of the cervico-cranial arteries using image data sets from a subsecond spiral CT
      scanner is useful for the visualization of anatomical and pathological
      abnormalities and offer a promising minimally invasive alternative compared with
      other diagnostic procedures.

PMID- 9533926
TI  - Effects of oxaceprol on the microcirculation in ischemia/reperfusion injury.
AB  - Oxaceprol, an established drug for treatment of degenerative joint disease, has
      recently been shown in vitro to reduce leukocyte adhesion to cultured endothelial
      cells and leukocyte extravasation in vivo in an arthritis animal model. The aim
      of this study was to examine the effects of Oxaceprol on the microcirculation of
      striated skin muscle. In the dorsal skinfold chamber of the awake Syrian golden
      hamster I/R injury was induced by applying a 4-hour complete pressure ischemia.
      Prior to the ischemia, after 30 minutes, 2 hours and 24 hours of reperfusion the
      following parameters were assessed in a blinded study: macromolecular leakage,
      leukocyte rolling fraction, adherent leukocytes, and functional capillary density
      (FCD). Rhodamine 6G to stain leukocytes in-vivo and FITC Dextran (MW 150,000) was
      used as a plasma marker. 15 minutes prior to reperfusion the animals received
      either an i.v. bolus infusion of Oxaceprol (50mg/kg) or an equivalent volume of
      saline, which was followed by a 45-minute continuous infusion at the same dose.
      At the conclusion of the experiment samples were collected from the chamber
      tissue for histological quantification of leukocyte extravasation using an
      esterase stain. Oxaceprol treatment resulted in a significant decrease of
      postischemic leukocyte adherence after 0.5 h and 2h of reperfusion. The
      histological sections revealed a significant reduction in the number of
      extravasated leukocytes. There was a reduction of macromolecular leakage and
      treatment also resulted in a preservation of tissue perfusion, as was indicated
      by a significant increase in FCD in the treatment group compared to the ischemia
      group. In summary, Oxaceprol was able to protect the tissue from
      ischemia/reperfusion injury.

PMID- 9533927
TI  - The early cardiovascular toll of cigarette smoking in dyslipidaemic patients in
      the United Kingdom.
AB  - Relationships between early cardiovascular risk at mean follow-up 1. 8 years and
      cigarette smoking status were investigated through analysis of data from
      participating clinics entered from 1981-1994 in the UK-Lipid Clinics Programme
      computerised database. Lipid profiles and new cardiovascular events were recorded
      for 3601 male, 4883 female human non-smokers mean age 44.7 and 53.1 years, 3077
      male, 2275 female current smokers age 46.3 and 50.3 years and 7210 male, 4559
      female age 49.2 and 53.3 years ever-smokers. Levels of triglycerides and total
      cholesterol increased across the gradient never/ex/current smoker, with a reverse
      gradient for HDL-cholesterol. Never-smokers were slightly lighter than other
      groups and males were younger, differences insufficient to explain the lipid
      variation. Minor differences in blood pressure between groups did not show this
      gradient and the development of new hypertension was not consistently related to
      smoking habits. In contrast the expression of newly-recorded cardiovascular
      disease was greater and in some categories doubled for current or ex-smokers in
      contrast with never-smokers. This survey emphasises first, the continuing
      inadequacy of stop-smoking support even at specialist clinics, second, that
      patients who give up smoking are to be congratulated and benefit in the long-term
      but third, that the change in status can be recent and classification as ex
      smoker can conceal high short-term risk, for which lipid profiles may also be
      significant and justify priority attention in management.

PMID- 9533928
TI  - Modulation of the cellular and humoral immune responses of tumor patients by
      mistletoe therapy.
AB  - There is evidence from recent data that mistletoe extracts exert
      immunostimulatory properties which could explain their therapeutic effects
      observed in some tumor patients. Aim of our study was, therefore, to investigate
      the effect of a subcutaneous 16-weeks therapy with a mistletoe extract
      (ABNOBAviscum Mali, AM) on the cellular and humoral immune responses in eight
      breast cancer patients. Mistletoe therapy induced a strong initial proliferation
      of peripheral blood mononuclear cells (PBMC) in all individuals, which, however,
      decreased in six patients during the observation period, indicating that not only
      activating but also inhibitory mechanisms have been induced. In all supernatants
      of AM-stimulated cell cultures TNF-alpha or IL-6 were found, indicating the
      activation of cells of the monocyte-/macrophage lineage by mistletoe extracts.
      Further analyses revealed, that AM induced in vitro also the release of low
      amounts of IFN-gamma and IL-4 with individual variations. At the end of the
      therapy, a shift to Th1- related cytokines could be observed in the in vitro cell
      culture system. All patients produced anti-mistletoe lectin 1 antibodies of the
      IgG-type during therapy and in four of them additionally antibodies of the IgE
      type were found. It, therefore, seems that AM can influence the Th1/Th2 balance
      and, in case of a Th1 shift, this may favourably influence the tumor growth.

PMID- 9533929
TI  - Efficacy and safety of iodine in the postpartum period in an area of mild iodine
      deficiency.
AB  - BACKGROUND: Iodine deficiency (even moderate) plays a major role in pregnancy
      associated goiter development, which is only party reversible after pregnancy.
      The prevalence of post partum thyroiditis is reported to be slightly lower in
      areas of iodine deficiency. Thus iodine supplementation may be effective in
      decreasing pregnancy associated increase in thyroid volume, but enhances the risk
      of increasing the prevalence of thyroid dysfunction in the post partum period.
      Therefore, we evaluated the effect of iodine supplementation (with two different
      doses: 50 microg and 250 microg) on the prevalence of post partum thyroiditis and
      the decrease in thyroid volume up to 8 months post partum in an area of mild
      iodine deficiency. PATIENTS AND METHODS: Thyroid volume of 56 women was evaluated
      5 days and 3 months after delivery (study I). In an intervention study (Study II)
      70 women were randomized to receive 50 or 250 microg of potassium iodide for a
      period of 8 months post partum beginning five days after delivery. Thyroid
      volume, the echogenecity of the thyroid gland, thyroid hormone parameters (T4,
      T3, fT4, TSH) and thyroid antibodies (TPO and Tg-Ab) were measured 5 days, 3 and
      8 months after delivery. RESULTS: A total number of 11 women developed postpartum
      thyroid dysfunction: 4 women developed manifest thyroid dysfunction (3
      hyperthyroidism and 1 hypothyroidism) 3 months post partum. The remaining seven
      had subclinical hypo- or hyperthyroidism. All changes were clinically mild and
      transient as evidenced by normalization of thyroid hormone parameters on
      reexamination at 8 months. Among the eleven, 6 women in the 50 microg iodine
      group and 5 women of the 250 microg iodine group developed thyroid dysfunction,
      suggesting that the iodine dose did not affect post partum thyroiditis. The
      administration of only 50 microg iodine was associated with a significant fall of
      thyroid size already 3 months after delivery (25.4 +/- 1.5 ml (mean +/- sem) to
      18.2 +/- 1.25 p <0.001). The application of 250 microg iodine was equally
      effective. 8 months post partum a slight but further decrease could be
      demonstrated. On the other hand, in study I no significant reduction in thyroid
      volume was observed in women receiving no supplementary iodine (thyroid volume at
      delivery 29 +/- 2.2 ml; at 3 months 27.5 +/- 3.0 ml. CONCLUSION: The
      administration of supplementary iodine (up to 250 microg) to an unselected
      population, residing in an area of mild iodine deficiency, in the post partum
      period is save as indicated by a prevalence of 5.7% manifest thyroid dysfunction.
      These changes are clinically mild and transient. Even the amount of 50 microg of
      iodine supplementation seems to by very efficient in reducing pregnancy
      associated increments in thyroid volume.

PMID- 9533930
TI  - Diatomaceous earth lowers blood cholesterol concentrations.
AB  - In this study a potential influence of diatomaceus earth to lower blood
      cholesterol was investigated. During 12 weeks we monitored serum lipid
      concentrations in 19 healthy individuals with a history of moderate
      hypercholesterinemia (9 females, 10 males, aged 35 - 67 years). Individuals
      administered orally 250 mg diatomaceous earth three-times daily during an 8 weeks
      observation period. Serum concentrations of cholesterol, high-density lipoprotein
      cholesterol, low-density lipoprotein cholesterol and triglycerides levels were
      measured before study entry, every second week during the period of diatomaceous
      earth intake and 4 weeks after stop of intake. Compared to baseline (285.8 +/-
      37.5 mg/dl = 7.40 +/- 0.97 mM) diatomaceous earth intake was associated with a
      significant reduction of serum cholesterol at any time point, reaching a minimum
      on week 6 (248.1 mg/dl = 6.43 mM, -13.2% from baseline; p<0.001). Also low
      density lipoprotein cholesterol (week 4: p<0.05) and triglycerides levels
      decreased (week 2: p<0.05, week 4: p<0.01). Four weeks after intake of
      diatomaceous earth was stopped, serum cholesterol, low-density lipoprotein
      cholesterol and triglycerides still remained low and also the increase of high
      density lipoprotein cholesterol became significant (p<0.05). Diatomaceous earth,
      a bioproduct, is capable of reducing blood cholesterol and positively influencing
      lipid metabolism in humans. Placebo-controlled studies will be necessary to
      confirm our findings.

PMID- 9533931
TI  - Congress Report: XIX symposium of the International Association for Comparative
      Research on Leukemia and Related Diseases, Mannheim/Heidelberg, Germany, July 13 
      18, 1997.
AB  - The XIX Symposium of the International Association for Comparative Research on
      Leukemia and Related Diseases (IACRLRD, President: Prof. Dr. R. Hehlmann) was
      held in Mannheim and Heidelberg, Germany, July 13 - 18, 1997. Comparative
      research in cancer was systematically established in the 1950s. Similarities in
      morphology, biology and pathology between animal and human leukemias and related
      diseases and the viral origin of a variety of animal leukemias and related
      diseases (lymphomas, sarcomas, breast tumors etc.) led to the concept that
      comparative research should promote the understanding of human leukemias and
      related diseases. In 1960 the World Health Organization inaugurated the
      establishment of a World Committee for Comparative Leukemia Research. The first
      symposium took place in Hannover, Germany, in 1963. After the fifth symposium in
      Padova, Italy, in 1971 the International Association for Comparative Research on
      Leukemia and Related Diseases (IACRLRD) was founded to complement the World
      Committee and to expand the international effort. The history of the symposium
      shows the evolution from a meeting on animal leukemia viruses into one dealing
      with viral and genetic aspects of human and animal leukemia and related diseases.
      The scientific evolution of the Abelson murine leukemia virus with its abl
      oncogene in the 1970s to what currently appears as the most reliable marker for
      human chronic myeloid leukemia is merely one example. Comparative research has
      reached a new dimension with the the recent advances in sequencing of the genomes
      of a variety of species and of humans. Many genes identified in the human genome
      and relevant for disease can be found in the genomes of animal species and even
      in the genomes of bacteria and of yeast. This reminds us that not just human and
      animal biology but also pathology must be regarded as a continuum of evolution
      and that much can be learned from comparing the genetic information of different
      species. Comparative genome research will allow conclusions to be drawn from
      principles recognized in animal species which are relevant to human diseases. It
      is likely that the application of comparative research to genome analysis will
      provide basic new insights in molecular medicine into the function of living
      beings for both animal species and humans. The current revolution in genomics is
      the latest phase in a rich history of medical progress related to the comparative
      approach. Meetings and organizations that have grown out of IACRLRD, include, at
      least to some extent: the Meeting of the International Human Retrovirology
      Association, the Gallo Lab Meeting , the Feline Retrovirus Meeting, the Cold
      Spring Habor Retrovirus Meeting, international and regional AIDS meetings, and
      many others. The XIX symposium in Mannheim included five memorial lectures, seven
      plenary sessions, 18 parallel sessions, two round table discussions and a public
      forum. In addition, six associated satellite symposia were held. The general
      meeting, attended by participants from 27 countries, integrated thematically
      contributions of genetic, cellular, and viral factors toward the development of
      leukemia and lymphoma and sought unifying concepts in leukemogenesis.

PMID- 9533933
TI  - Eosinophils retain their granule major basic protein in a murine model of
      allergic pulmonary inflammation.
AB  - Accumulation of eosinophils in the lung with concomitant tissue damage are
      defining histopathologic features of human asthma. Through degranulation and the
      release of proinflammatory proteins such as major basic protein (MBP),
      eosinophils may perpetuate this inflammatory response. We investigated the extent
      of eosinophil degranulation in a murine model of allergic pulmonary inflammation.
      In this paradigm, the mice develop pulmonary eosinophilia, mucus hypersecretion,
      tissue damage, and airway edema and hyperreactivity. To evaluate the degree of
      eosinophil degranulation, we used a polyclonal antibody to murine MBP (mMBP) to
      perform dot blot analysis of bronchoalveolar lavage (BAL) cells and fluids, and
      immunohistochemical fluorescent analysis of lung tissue sections. After ovalbumin
      antigen challenge, we were unable to detect immunoreactive mMBP in the BAL fluids
      from either nonsensitized or sensitized mice. However, after lysis of the
      recoverable BAL cells, we were able to detect mMBP by immunoblot analysis, with
      the levels of immunoreactive mMBP directly related to the number of recoverable
      eosinophils. We also examined paraffin-embedded, lung tissue sections for
      patterns of mMBP deposition. Whereas lung sections from allergic mice revealed
      prominent peribronchial eosinophilia after antigen challenge, tissue sections
      from nonsensitized animals rarely displayed eosinophils. Despite the presence of
      numerous eosinophils, no immunohistologic evidence of extracellular mMBP could be
      found in antigen-challenged allergic mice. Furthermore, rechallenged allergic
      mice displayed a significant increase in the number of recruited pulmonary
      eosinophils but all immunoreactive mMBP was still intracellular. We conclude that
      the recruited pulmonary eosinophils have not substantially degranulated. These
      results suggest that, in this murine model of allergic inflammation, eosinophil
      degranulation and release of mMBP does not contribute to the observed pulmonary
      inflammation and airway hyperreactivity.

PMID- 9533932
TI  - CTLA4Ig inhibits airway eosinophilia and hyperresponsiveness by regulating the
      development of Th1/Th2 subsets in a murine model of asthma.
AB  - Complete T-cell activation requires two distinct signals, one delivered via the T
      cell receptor, and the second "co-stimulatory" signal through CD28/B7 ligation.
      Previous studies showed that the blockade of CD28/B7 ligation alters
      differentiation of Th1/Th2 lymphocyte subsets in vitro and in vivo. The present
      study was designed to determine the effect of a CD28/B7 antagonist (CTLA4Ig) on
      Th1/Th2 development in Schistosoma mansoni-sensitized and airway-challenged mice.
      Treatment of mice with CTLA4Ig beginning 1 wk after sensitization abolished
      airway responsiveness to intravenous methacholine determined 96 h following
      antigen challenge. We also found a significant reduction in bronchoalveolar
      lavage (BAL) eosinophilia, and reduced peribronchial eosinophilic infiltration
      and mucoid-cell hyperplasia. Furthermore, CTLA4Ig treatment significantly
      decreased interleukin (IL)-4 and IL-5 content in BAL fluid in vivo, and the
      production of IL-5 by lung lymphocytes stimulated with soluble egg antigen (SEA)
      in vitro. In contrast, the content of interferon-gamma in BAL fluid and
      supernatant from SEA-stimulated lung lymphocytes from CTLA4Ig-treated mice was
      increased significantly compared with untreated animals. Thus, CTLA4Ig inhibits
      eosinophilic airway inflammation and airway hyperresponsiveness in S. mansoni
      sensitized and airway-challenged mice, most likely due to attenuated secretion of
      Th2-type cytokines and increased secretion of Th1-type cytokines.

PMID- 9533934
TI  - Ozone alters the expression of tenascin-C in cultured primate nasal epithelial
      cells.
AB  - Tenascin-C is an extracellular matrix component which is transiently expressed in
      association with epithelial cell detachment, proliferation, and migration. This
      molecule has been identified in respiratory tissue, but little is known about the
      cellular source of tenascin-C or the factors that regulate its production. Since
      air pollutants are known to disrupt epithelial integrity, we investigated the
      regulation of tenascin-C in response to 0.3 ppm ozone in differentiated primate
      nasal epithelial cells in culture at an air-medium interface. The expression of
      tenascin-C was upregulated in response to ozone, as determined by Northern blot
      analysis, Western blotting, and immunofluorescent staining. In contrast, there
      was no change in the mRNA levels for versican, biglycan, perlecan, or collagen
      type I. Reduced cellular attachment to the substrate was evident in ozone-treated
      cultures in association with tenascin-C deposition at the interfaces between
      cells and basal surfaces. The presence of tenascin-C on denuded areas of the
      matrix suggests that tenascin-C may have been instrumental in the loss of patches
      of cells. The modulation of tenascin-C synthesis and distribution may play a
      significant role in the response of respiratory epithelial cells to ozone
      exposure.

PMID- 9533935
TI  - Cyclooxygenase isoenzyme localization and mRNA expression in rat lungs.
AB  - Prostanoid generation may proceed via both isoforms of cyclooxygenase, Cox-1 and
      Cox-2. Cox-1 is thought to be ubiquitously expressed, whereas Cox-2 is mostly
      assumed to be dynamically regulated, responding to inflammatory stimuli. The
      cellular localization of Cox-1 and Cox-2 in the lung, an organ with high
      cyclooxygenase activity, is not known. In normal rat lungs the expression and
      localization of Cox-1 and Cox-2 were examined with immunogold-silver staining and
      the RT-PCR technique. Quantitative image analysis of the staining intensity was
      performed by measuring mean gray values of digitized epipolarization images.
      Expression of both Cox-1 and Cox-2 was readily detectable in rat lungs. Cox-1
      immunoreactivity localized predominantly to bronchial epithelial cells, smooth
      muscle cells of large hilum veins, and (with lower expression) to alveolar
      macrophages and pulmonary artery endothelial cells. The most intense Cox-2
      staining was noted in macrophage- and mast cell-like cells, detected in close
      vicinity to the bronchial epithelium and in the connective tissue surrounding the
      vessels. In addition, strong Cox-2 expression was found in smooth muscle cells of
      partially muscular vessels and large veins of the hilum. Bronchial epithelial
      cells displayed Cox-2 immunoreactivity with limited intensity. Alveolar
      macrophages and alveolar septal cells were only occasionally stained with anti
      Cox-2 antibodies. Both Cox-1 and Cox-2 are constitutively expressed in several
      cell types of normal rat lung, but display clearly different patterns of cellular
      localization. Cox-2 may not be related only to lung inflammation, but is
      suggested to be implicated in regulatory processes under physiological conditions
      as well.

PMID- 9533936
TI  - Macrophage-stimulating protein and its receptor in non-small-cell lung tumors:
      induction of receptor tyrosine phosphorylation and cell migration.
AB  - Previously, we identified macrophage-stimulating protein (MSP) as being expressed
      during hamster lung injury induced by nitrosamine carcinogens. Transient,
      generalized epithelial-cell hyperplasia during the preneoplastic period, and
      eventually nonneuroendocrine (non-NE) lung tumors, are known to develop in these
      nitrosamine-treated hamsters. We wished to test the hypothesis that MSP and its
      tyrosine kinase receptor, RON, might represent an autocrine/paracrine system
      involved in the pathogenesis of human nonneuroendocrine lung tumors, the non
      small-cell carcinomas (NSCLCs). We found that this occurred in a paracrine
      fashion in three of eight primary human NSCLCs that expressed messenger RNA
      (mRNA) for MSP at high levels in histologically normal lung adjacent to the
      tumor, but not in the primary tumor, together with mRNA for RON in both normal
      and tumor tissue. MSP and RON could also constitute an autocrine/paracrine system
      in human NSCLC cell lines: five of 16 cell lines (squamous and adenosquamous)
      expressed both MSP and RON; and an additional five of 16 cell lines expressed RON
      without detectable MSP. Although three cases of primary squamous-cell carcinomas
      expressed MSP (two of three in the tumor and one of three in nonneoplastic lung),
      mRNA for RON was not detectable in these cases. RON was functional in all tested
      RON mRNA-positive cell lines, with exogenous MSP inducing RON-mediated tyrosine
      phosphorylation. Treatment of a RON-positive adenosquamous carcinoma cell line
      with MSP additionally resulted in increased motility in a cell-migration assay,
      suggesting that MSP might promote cell migration of some NSCLCs. In conclusion,
      MSP and RON might represent an autocrine/paracrine system involved in the
      pathogenesis of lung cancer, although the nature of the biologic responses in
      different cell types might vary considerably.

PMID- 9533937
TI  - Mast cell collagenase correlates with regression of pulmonary vascular remodeling
      in the rat.
AB  - Pulmonary vascular remodeling, produced by cell hypertrophy and extracellular
      matrix protein synthesis in response to hemodynamic stress, regresses after
      reduction of blood pressure, possibly by proteolysis of structural proteins. To
      test this postulate, we assessed the breakdown of extracellular matrix proteins
      and expression of collagenase and elastase in pulmonary arteries of rats exposed
      to hypoxia (10% O2 for 10 d) followed by normoxia. During hypoxia, contents of
      collagen and elastin increased in pulmonary arteries and latent rat interstitial
      collagenase was expressed without increased collagenolytic activity or mRNA
      levels. At 3 days after normoxia, collagen and elastin contents decreased
      coincident with the new appearance of activated collagenase and transient
      increases in collagenolytic and elastolytic activities. The amount of
      immunoreactive collagenase, localized predominately in connective tissue-type
      mast cells, was increased in the adventitia and media of hypertensive vessels. We
      conclude that mast cells containing latent collagenase are recruited into the
      outer walls of pulmonary arteries during remodeling. It is possible that mast
      cell-derived collagenase contributes to collagen breakdown in pulmonary arteries
      during early recovery from hypoxia and plays a role in restoration of vascular
      architecture.

PMID- 9533939
TI  - Modulation of monocyte chemotactic protein-1 production by hyperoxia: importance
      of RNA stability in control of cytokine production.
AB  - Pulmonary oxygen toxicity occurs after prolonged administration of increased
      fractions of inspired oxygen. Lung damage in this setting manifests as diffuse
      alveolar damage. In animals exposed to hyperoxia, increased numbers of alveolar
      macrophages are noted 72 h after initiation of high concentrations of oxygen.
      Monocyte chemotactic protein-1 (MCP-1) is a cytokine released by a number of cell
      types that has potent chemotactic activity for monocytes, precursor cells for
      alveolar macrophages. In the current study, we examined whether MCP-1 production
      was increased in response to hyperoxia. We used the monocyte/ histiocytic U937
      cell line and exposed these cells to hyperoxia for variable amounts of time, then
      determined MCP-1 concentrations by enzyme-linked immunosorbent assay and MCP-1
      mRNA levels by Northern blot analysis. We also examined the effects of
      dexamethasone on the response of U937 cells to hyperoxia. Finally, as a potential
      mechanism for regulation of U937 MCP-1 production, we examined effects of
      hyperoxia on MCP-1 mRNA stability. The results demonstrate that hyperoxia
      stimulates MCP-1 production after 6 and 24 h of exposure. MCP-1 mRNA levels are
      also increased after initiation of hyperoxia in part through effects on MCP-1
      transcript stability. Dexamethasone significantly reduces MCP-1 production and
      mRNA levels also in part through effects on transcript stability. These studies
      suggest monocytes may be attracted to hyperoxia-exposed lungs through enhanced
      MCP-1 production. MCP-1 production appears to be upregulated in part through post
      transcriptional processes in this setting.

PMID- 9533938
TI  - Oncostatin M is a potent stimulator of alpha1-antitrypsin secretion in lung
      epithelial cells: modulation by transforming growth factor-beta and interferon
      gamma.
AB  - alpha1-Antitrypsin (alpha1-AT) plays a key role in lung homeostasis. Although the
      hepatocyte is considered as the primary source of alpha1-AT, we have previously
      demonstrated that rat alveolar epithelial type II cells as well as the human A549
      cell line synthesize alpha1-AT, suggesting its local production within the lung.
      In the present study, we showed that oncostatin M, as opposed to interleukin
      1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), or IL-6, is a potent
      stimulator of alpha1-AT synthesis in the human A549 cell line. The oncostatin M
      induced alpha1-AT secretion is modulated by interferon-gamma (IFN-gamma) and
      transforming growth factor-beta (TGF-beta) at both the protein and mRNA levels.
      IFN-gamma decreases oncostatin M-induced alpha1-AT secretion. By contrast, TGF
      beta in combination with oncostatin M induces a dramatic and synergistic
      upregulation that is not observed in the HepG2 hepatocyte cell line. Our results
      suggest that during an inflammatory process, alveolar epithelial cells may
      contribute to the antiprotease defense within the lung.

PMID- 9533940
TI  - Expression of RANTES by bronchoalveolar lavage cells in nonsmoking patients with
      interstitial lung diseases.
AB  - Emphasis has recently been placed on the roles of chemotactic cytokines called
      chemokines to explain the accumulation of inflammatory cells in the lung that may
      precede or accompany pulmonary fibrosis in interstitial lung diseases. We
      hypothesized that RANTES, a member of the C-C chemokines, is one such chemokine.
      Bronchoalveolar lavage was done in 20 patients with sarcoidosis, 10 patients with
      interstitial pneumonia associated with collagen vascular disease (CVD-IP), 10
      patients with idiopathic pulmonary fibrosis (IPF), and eight healthy volunteers
      (HV), all of whom were never-smokers. We semiquantitated the spontaneous RANTES
      mRNA expression by a competitive reverse transcription-polymerase chain reaction
      (RT-PCR) technique, and measured the levels of RANTES protein by enzyme-linked
      immunosorbent assay. In all disease groups the expression of RANTES mRNA by
      bronchoalveolar lavage fluid (BALF) cells and the levels of RANTES protein in
      BALF were significantly increased compared with those in HV. Patients with
      sarcoidosis and CVD-IP had a significant positive correlation between the
      expression of RANTES mRNA by BALF cells and BALF lymphocytosis. The amounts of
      RANTES mRNA expressed by peripheral blood mononuclear cells and the levels of
      RANTES protein in serum did not differ among all study groups. Our study
      demonstrates the adaptability of a semiquantitative RT-PCR method for determining
      cytokine mRNA expression in vivo. Our results suggest that RANTES may be one of
      the chemokines that are involved in the mechanism for the accumulation of
      inflammatory cells in the lung of some distinct interstitial lung diseases.

PMID- 9533941
TI  - Visna-maedi virus induces interleukin-8 in sheep alveolar macrophages through a
      tyrosine-kinase signaling pathway.
AB  - The mechanisms leading to the severe lung damage seen in some sheep naturally
      infected with the visna-maedi virus, and to pulmonary lesions in other lentiviral
      diseases, appear to involve the recruitment of large numbers of uninfected
      inflammatory cells. Only a few alveolar macrophages from experimentally infected
      lambs express virus, but high levels of interleukin (IL)-8 mRNA are present in
      the macrophage population. In vitro infection with visna-maedi virus at low
      multiplicity of alveolar macrophages from uninfected sheep also strongly induced
      the expression of IL-8 mRNA and the accumulation of IL-8 in the extracellular
      medium. An initial peak of IL-8 mRNA expression at 3 or 6 h after infection was
      followed by a fall, then a more persistent expression lasting at least 48 h after
      infection. The early peak was accompanied by expression of mRNA for IL-1beta, and
      a possible rise in tumor necrosis factor alpha (TNFalpha) mRNA, although this was
      frequently elevated in uninfected ovine alveolar macrophages. Interestingly,
      these events occurred identically in cells treated with non-infectious heat
      treated virus, suggesting that interaction between viral components and cellular
      membrane receptors could suffice for both early and late IL-8 induction. The
      level of IL-8 mRNA induced by treatment with live or inactivated virus could be
      severely reduced by pretreatment of the macrophages with genistein but not with
      staurosporine, suggesting the involvement of a tyrosine-kinase signaling pathway.
      The early induction of IL-1beta and possibly of TNFalpha may explain the
      occurrence of a later persistent expression of IL-8 mRNA through an autocrine
      mechanism.

PMID- 9533942
TI  - Transgenic models for the study of lung antioxidant defense: enhanced manganese
      containing superoxide dismutase activity gives partial protection to B6C3 hybrid
      mice exposed to hyperoxia.
AB  - To investigate the role of manganese-containing superoxide dismutase (MnSOD) in
      lung antioxidant defense, lines of transgenic B6C3 hybrid mice carrying human
      MnSOD transgenes under the transcriptional control of a human beta-actin promoter
      were established. Expression studies demonstrated that the human MnSOD transgene
      in line TgHMS66 is expressed and functional. The cellular distribution of the
      transgene product in the lungs was further examined by immunocytochemical
      analysis. Increased immunoreactive MnSOD was found in mitochondria of lung type I
      epithelial cells, type II epithelial cells, capillary endothelial cells, and
      fibroblasts. Furthermore, the magnitude of increase in mitochondrial labeling
      density of type II cells of nontransgenic, hemizygous, and homozygous transgenic
      littermates was proportional to the increased lung activity of MnSOD found in
      these mice. Transgenic mice over-expressing MnSOD did not have enhanced survival
      relative to controls when exposed to > 99% oxygen. However, when exposed to 90%
      oxygen, the transgenic mice had a small but statistically significant increase in
      survival time. Our results indicate that when the beta-actin promoter is used to
      increase activity of MnSOD it provides modest protection to B6C3 mice against
      hyperoxic lung injury.

PMID- 9533943
TI  - Isolation and molecular characterization of serous and mucous gland cells of the
      porcine airways.
AB  - Secretory cells of the glands of the airways play important roles in the
      pathogenesis of several diseases. Little, however, is known about the molecular
      biology of these cells. Here we describe a procedure for the separation of serous
      and mucous gland cells and the isolation of genes specifically expressed in these
      cells. Mucosal tissue was prepared from porcine large airways. Following
      enzymatic digestion, the cell types were separated by discontinuous Percoll
      density gradient centrifugation. Cell purity was analyzed by electron microscopy.
      The cell fractions contained between 75 and 85% mucous and serous cells,
      respectively. To isolate cell type-specific genes, poly(A)+ RNA was isolated from
      serous and mucous cell fractions, reverse transcribed and used for differential
      display polymerase chain reaction (PCR). Out of about a total of 1,700 PCR
      products identified in horizontal polyacrylamide gels, most bands were found to
      be common to both cell fractions, indicating that the transcript patterns in
      cells from both fractions are very similar. Eighteen PCR products, however, were
      consistently distinct in the two cell fractions, with eight products present only
      in RNA from the mucous cell fraction and 10 PCR products present only in RNA from
      the serous cell fraction. Dot-blot analysis of mRNA of serous and mucous cells
      proved the cell type-specific expression of nine PCR products. Northern blot
      analysis detected single transcripts for each PCR product. The development of a
      simple cell separation procedure for secretory cells of the airways, combined
      with the ability to isolate numerous cell type-specific marker genes, should
      facilitate the molecular understanding of secretory cells of the airways.

PMID- 9533944
TI  - Keratinocyte growth factor modulates alveolar epithelial cell phenotype in vitro:
      expression of aquaporin 5.
AB  - We investigated the role of keratinocyte growth factor (KGF) in regulation of
      alveolar epithelial cell (AEC) phenotype in vitro. Effects of KGF on cell
      morphology, expression of surfactant apoproteins A, B, and C (SP-A, -B, and -C),
      and expression of aquaporin 5 (AQP5), a water channel present in situ on the
      apical surface of alveolar type I (AT1) cells but not expressed in alveolar type
      II (AT2) cells, were evaluated in AECs grown in primary culture. Observations
      were made on AEC monolayers grown in serum-free medium without KGF (control) or
      grown continuously in the presence of KGF (10 ng/ml) from either Day 0 (i.e., the
      time of plating) or Day 4 or 6 through Day 8 in culture. AECs monolayers express
      AQP5 only on their apical surfaces as determined by cell surface biotinylation
      studies. Control AECs grown in the absence of KGF through Day 8 express
      increasing levels of AQP5, consistent with transition toward the AT1 cell
      phenotype. Exposure of AECs to KGF from Day 0 results in decreased AQP5
      expression, retention of a cuboidal morphology, and greater numbers of lamellar
      bodies relative to control on Day 8 in culture. AECs treated with KGF from Day 4
      or 6 exhibit a decrease in AQP5 expression through subsequent days in culture, as
      well as an increase in expression of surfactant apoproteins. These data, showing
      that KGF both prevents and reverses the increase in AQP5 (and decrease in
      surfactant apoprotein) expression that accompanies progression of the AT2 toward
      the AT1 cell phenotype, support the concepts that transdifferentiation between
      AT2 and AT1 cell phenotypes is at least partially reversible and that KGF may
      play a major role in modulating AEC phenotype.

PMID- 9533945
TI  - Hydrogen peroxide activates extracellular signal-regulated kinase via protein
      kinase C, Raf-1, and MEK1.
AB  - We have previously demonstrated that hydrogen peroxide (H2O2) treatment of bovine
      tracheal myocytes increases the activity of extracellular signal-regulated
      kinases (ERK), serine/threonine kinases of the mitogen-activated protein (MAP)
      kinase superfamily thought to play a key role in the transduction of mitogenic
      signals to the cell nucleus. Moreover, H2O2-induced ERK activation was partially
      reduced by pretreatment with phorbol 12,13-dibutyrate, which depletes protein
      kinase C (PKC). In this study, we further examined the signaling intermediates
      responsible for ERK activation by H2O2 in airway smooth muscle, focusing on MAP
      kinase/ERK kinase (MEK), a dual-function kinase which is required and sufficient
      for ERK activation in bovine tracheal myocytes; Raf-1, a serine/threonine kinase
      known to activate MEK; and PKC. Pretreatment of cells with inhibitors of MEK
      (PD98059), Raf-1 (forskolin), and PKC (chelerythrine) each reduced H2O2-induced
      ERK activity. In addition, H2O2 treatment significantly increased both MEK1 and
      Raf-1 activity. No activation of MEK2 was detected. Together these data suggest
      that H2O2 may stimulate ERK via successive activation of PKC, Raf-1, and MEK1.

PMID- 9533946
TI  - Manganese superoxide dismutase in healthy human pleural mesothelium and in
      malignant pleural mesothelioma.
AB  - We hypothesized that manganese superoxide dismutase (MnSOD), known to be induced
      in rat mesothelial cells by asbestos fibers, cytokines, and hyperoxia, may also
      be induced in asbestos-related pleural diseases such as mesothelioma. MnSOD was
      assessed in healthy human pleural mesothelium (n = 6), in biopsy samples of human
      pleural mesothelioma (n = 7), in transformed nonmalignant human mesothelial cells
      (Met5A), and in two human mesothelioma cell lines (M14K and M38K) established
      from the tumor tissue of mesothelioma patients. There was no MnSOD
      immunoreactivity in five of the six samples of healthy pleural mesothelium,
      whereas MnSOD immunoreactivity was high in the tumor cells in all the
      mesothelioma samples. Northern blotting, immunohistochemistry, Western blotting,
      and specific activity measurements showed lower MnSOD in the nonmalignant Met5A
      mesothelial cells than in the M14K and M38K mesothelioma cells. In additional
      experiments the mesothelial and mesothelioma cells were exposed to menadione,
      which generates superoxide intracellularly, and to epirubicin, a cytotoxic drug
      commonly used to treat mesothelioma. The M38K mesothelioma cells were most
      resistant to menadione and epirubicin when assessed by LDH release or by adenine
      nucleotide (ATP, ADP, and AMP) depletion. These same cells showed not only the
      highest MnSOD levels, but also the highest mRNA levels and activities of
      catalase, whereas glutathione peroxidase and glutathione reductase levels did not
      differ significantly. We conclude that MnSOD expression is low in healthy human
      pleural mesothelium and high in human malignant mesothelioma. The most resistant
      mesothelioma cells contained coordinated induction of MnSOD and catalase.

PMID- 9533947
TI  - Expansions of T-cell subsets expressing particular T-cell receptor variable
      regions in chronic beryllium disease.
AB  - Chronic beryllium disease (CBD) is a granulomatous disorder characterized by the
      presence of noncaseating granulomas and mononuclear cell inflammation, occurring
      in 1 to 5% of people exposed to beryllium in the workplace. In the lungs of
      affected patients, CD4(+) T cells accumulate. Using anti-T-cell receptor (TCR)
      monoclonal antibodies, we investigated the TCR beta and alpha variable (Vbeta and
      Valpha, respectively) repertoire in the bronchoalveolar lavage (BAL) and blood of
      both CBD patients and healthy controls. There was marked heterogeneity within the
      BAL CD4(+) T-cell repertoire in both patients and controls. However, 11 of the 28
      CBD patients demonstrated 16 different T-cell subset expansions within the BAL as
      compared with only one expansion in ten healthy controls. Five of the 16
      expansions in CBD patients expressed Vbeta3. Altered TCR expression within the
      BAL T-cell repertoire appeared to persist over time in patients who underwent
      repeat evaluation. After in vitro stimulation of BAL T cells with beryllium
      sulfate and interleukin-2, we noted further alteration of the BAL TCR repertoire
      in some individuals. These results provide additional insight into the
      involvement of CD4(+) T cells in this disease and form the basis for studies to
      examine the nature of the stimulating antigen.

PMID- 9533948
TI  - The orphan receptor BmHNF-4 of the silkmoth Bombyx mori: ovarian and zygotic
      expression of two mRNA isoforms encoding polypeptides with different activating
      domains.
AB  - Two silkmoth nuclear receptor isoforms, BmHNF-4a and BmHNF-4b, that are related
      to the mammalian orphan receptor HNF-4, were characterized. Their
      characterization revealed that they differ from each other only in their 5' UTR
      and N-terminus of the predicted polypeptides. In ovarian tissue, the two
      receptors are expressed as a delayed response to 20-hydroxy-ecdysone and their
      expression increases during vitellogenesis. BmHNF-4 mRNA is localized in the
      cytoplasm of follicular cells and a binding activity that recognizes a mammalian
      HNF-4 response element is present in follicular cell nuclear extracts. BmHNF-4
      mRNA is also present in the oocyte, the unfertilized egg and the early embryo,
      thus displaying a behavior reminiscent of maternal mRNA. Both mRNA isoforms are
      found in the embryo following fertilization and their abundance is modulated
      during ensuing embryogenesis. In contrast to the rather limited distribution of
      HNF-4 in mammalian tissues, BmHNF-4 is expressed in most larval and pharate adult
      tissues of the silkmoth.

PMID- 9533949
TI  - The prechordal midline of the chondrocranium is defective in Goosecoid-1 mouse
      mutants.
AB  - Gsc-1 expression marks cells with Spemann organizer, or axis-inducing, activity
      in the vertebrate gastrula. Gsc-1 knockouts, however, did not display phenotypes
      related to the early phase of expression. In this paper, additional phenotypes
      for the Gsc-1 mouse mutant are presented. Examination of the base of the cranium
      in the dorsal view revealed fusions and deletions in the midline of the
      prechordal chondrocranium. These defects were correlated with the sites of
      expression of Gsc-1 in the prechordal plate/foregut endoderm in the day 7.5/8.5
      embryo. Gsc-1 expression in proximal limb buds was correlated with malformations
      of the shoulder and hip articulations. In addition, ribs in the seventh cervical
      vertebra were observed with low penetrance. The role of Gsc-1 during gastrulation
      and axial development is discussed in relation to possible compensatory
      interactions with other genes such as HNF-3beta and the recently identified Gsc-2
      and Gsc-3 genes.

PMID- 9533950
TI  - Msg1 and Mrg1, founding members of a gene family, show distinct patterns of gene
      expression during mouse embryogenesis.
AB  - Msg1 and Mrg1 are founding members of a gene family which exhibit distinct
      patterns of gene expression during mouse embryogenesis. Sequence analysis reveals
      that these genes are unlike any other gene identified to date, but they share two
      near-identical sequence domains. The Msg1 and Mrg1 expression profiles during
      early development are distinct from each other. Msg1 is predominantly expressed
      in nascent mesoderm, the heart tube, limb bud and sclerotome. Intriguingly, Msg1
      expression is restricted, within these developing mesodermal sites, to posterior
      domains. Mrg1 is expressed prior to gastrulation in the anterior visceral
      endoderm. Expression is maintained in the endoderm once gastrulation has begun
      and commences in the rostralmost embryonic mesoderm which underlies the anterior
      visceral endoderm. Mrg1 expression persists in this rostral mesoderm as it is
      translocated caudalwards during the invagination of the foregut and the formation
      of the heart. Later Mrg1 expression predominates in the septum transversum caudal
      to the heart. This expression pattern suggests that the septum transversum
      originates from the rostralmost embryonic mesoderm which first expressed Mrg1 at
      the late primitive streak stage.

PMID- 9533951
TI  - Analysis of the developing Xenopus tail bud reveals separate phases of gene
      expression during determination and outgrowth.
AB  - We have studied Xenopus tail development from the end of gastrulation to the
      commencement of outgrowth at the tail bud stage. We show that an early group of
      genes are expressed at the stage of tail bud determination, at the end of
      gastrulation, and a late group are expressed at around stage 27 just before tail
      bud outgrowth. Together, these genes define seven distinct regions of the tail
      bud as outgrowth commences. We have previously shown that formation of a tail bud
      depends on the interaction of three tissue regions, called N, M and C, at stage
      13. Here we show that expression of the late group of genes is dependent on this
      NMC interaction. We describe molecular correlates of two of these regions, M and
      C, which were formerly unobservable and whose existence was inferred from
      embryological experiments.

PMID- 9533952
TI  - The suppressor of forked protein of Drosophila, a homologue of the human 77K
      protein required for mRNA 3'-end formation, accumulates in mitotically-active
      cells.
AB  - The suppressor of forked (Su(f)) protein of Drosophila melanogaster is highly
      homologous to two proteins involved in mRNA 3'-end formation, the yeast RNA14
      protein and the 77K subunit of human cleavage stimulation factor (CstF). This
      suggests a role for su(f) in mRNA 3'-end-processing, probably as part of
      Drosophila CstF. We have investigated the expression pattern of su(f) during
      Drosophila development and found that the su(f) gene product is not detected
      ubiquitously. The Su(f) protein accumulates in mitotically-active cells, but does
      not in non-dividing cells. This expression pattern corroborates earlier data
      suggesting that the phenotypes of su(f) mutants could result from a defect in
      cell proliferation. Our results suggest that, in Drosophila, Su(f) is involved in
      the regulatory function of CstF.

PMID- 9533953
TI  - bagpipe-Dependent expression of vimar, a novel Armadillo-repeats gene, in
      Drosophila visceral mesoderm.
AB  - Two homeobox-containing genes, tinman and bagpipe, play important roles during
      the specification of the midgut visceral musculature from the mesoderm during
      Drosophila embryogenesis. Expression of tinman in the dorsal mesoderm activates
      the expression of the bagpipe gene in segmental subsets of those cells, which
      then become determined to form the midgut visceral mesoderm. Understanding how
      the bagpipe gene affects this specification requires the isolation and
      characterization of its downstream target genes. Using an enhancer trap line that
      expresses its marker in the midgut visceral mesoderm, we have cloned and
      characterized a novel gene (vimar) that is expressed embryonically in the mid and
      hindgut visceral mesoderm, as well as in the CNS and PNS. The expression of this
      gene in the midgut visceral mesoderm initiates shortly after bagpipe expression
      and depends on bagpipe function. Maternal and zygotic transcripts are produced
      from this gene by alternative polyadenylation, and encode the same 634-amino acid
      protein. The vimar protein contains 15 tandem copies of the Armadillo repeat, a
      protein interaction domain, and is similar to mammalian Smg guanine dissociation
      stimulator protein, which stimulates the activity of a number of different p21
      small G-proteins. These results, together with the observed lethality of vimar
      mutations, indicate that vimar is one of the bagpipe target genes that are
      required for normal development and differentiation of the midgut visceral
      mesoderm.

PMID- 9533954
TI  - Control of anteroposterior and dorsoventral domains of Nkx-6.1 gene expression
      relative to other Nkx genes during vertebrate CNS development.
AB  - Here we report the isolation, sequence and developmental expression in the
      central nervous system of several members of the chicken and mouse Nkx gene
      family. These are among the earliest genes to be regionally expressed in the
      neural plate; they are expressed just above the axial mesendoderm (prechordal
      mesendoderm and notochord). Each Nkx gene has a distinct spatial pattern of
      expression along the anterior-posterior axis of the ventral central nervous
      system: Nkx-2. 2 is expressed along the entire axis, whereas Nkx-2.1 is
      restricted to the forebrain, and Nkx-6.1 and Nkx-6.2 are largely excluded from
      the forebrain. They are also expressed in distinct patterns along the dorsal
      ventral axis. These genes are expressed in both the ventricular and mantle zones;
      in the mantle zone Nkx-6.1 is co-expressed with Islet-1 in a subset of motor
      neurons. Like other Nkx genes, expression of Nkx-6.1 is induced by the axial
      mesendoderm and by sonic hedgehog protein. BMP-7 represses Nkx-6.1 expression.
      While the notochord can induce Nkx-6.1 expression in the anterior neural plate,
      sonic hedgehog protein does not, suggesting that the notochord produces
      additional molecules that can regulate ventral patterning.

PMID- 9533955
TI  - Epithelium-specific adenoviral transfer of a dominant-negative mutant TGF-beta
      type II receptor stimulates embryonic lung branching morphogenesis in culture and
      potentiates EGF and PDGF-AA.
AB  - Although exogenous transforming growth factor-beta (TGF-beta) is known to inhibit
      branching morphogenesis in mouse embryonic lungs in culture, whether the
      principal negative function of endogenous TGF-beta signaling resides in lung
      epithelium or mesenchyme remains unresolved. A recombinant adenovirus was
      constructed, containing a mutated human TGF-beta type II receptor with a
      truncated cytoplasmic kinase domain. We examined whether this dominant-negative
      receptor could abolish epithelium-specific endogenous TGF-beta signaling. We
      introduced the recombinant adenovirus into lung explants via intra-tracheal micro
      injection. This resulted in over-expression of exogenous truncated TGF-beta type
      II receptor only in airway epithelium, not in mesenchyme, as assessed by mRNA
      level and protein localization. Blockade of endogenous TGF-beta receptor
      signaling in epithelial endoderm by the mutated dominant-negative TGF-beta type
      II receptor resulted in significant (65%) stimulation of epithelial branching
      morphogenesis, while exogenous TGF-beta no longer downregulated epithelial PCNA
      immunoreactivity and surfactant protein C (SP-C) expression. Additionally, the
      mitogenic responses to epidermal growth factor (EGF) and platelet-derived growth
      factor, PDGF-AA were potentiated by 33 and 31%, respectively. We conclude that
      epithelium-specific adenovirus-mediated over-expression of a dominant-negative
      TGF-beta type II receptor completely and specifically abolished the anti
      proliferative effects of both endogenous and exogenous TGF-beta. Therefore,
      epithelium-specific TGF-beta signaling is sufficient to negatively regulate
      embryonic lung-branching morphogenesis in culture. We speculate that abrogation
      of TGF-beta signaling stimulates lung morphogenesis by potentiating the inductive
      and permissive effects of other endogenous peptide growth factors such as EGF and
      PDGF-AA.

PMID- 9533956
TI  - Xenopus cadherin-11 (Xcadherin-11) expression requires the Wg/Wnt signal.
AB  - In this study we describe the isolation of Xcadherin-11, the Xenopus homologue to
      the mesenchymal cadherin-11. Similar to epithelial and neural cadherins,
      overexpression of Xcadherin-11 led to posteriorised phenotypes due to inhibition
      of convergent extension movement. Because zygotic expression of Xcadherin-11
      starts with gastrulation, we analysed the ability of different growth factors
      involved in mesoderm differentiation to induce the expression of Xcadherin-11.
      Using the animal cap assay, we demonstrated that Xcadherin-11 is activated by
      Xwnt-8 or beta-catenin, but repressed by BMP-4. Activin did not induce Xcadherin
      11 but its synergistic function was required for the Xwnt-8/beta-catenin-mediated
      activation of Xcadherin-11. Because Xcadherin-11 and Xenopus E- and N-cadherin
      are differentially regulated by growth factors in the Xenopus animal cap, our
      results also reveal that this assay provides a helpful model system to elucidate
      the molecular control mechanism of epithelial-mesenchymal conversion.

PMID- 9533957
TI  - Anterior specification of embryonic ectoderm: the role of the Xenopus cement
      gland-specific gene XAG-2.
AB  - In a search for novel developmental genes expressed in a spatially restricted
      pattern in dorsal ectoderm of Xenopus we have identified XAG-2, a cement gland
      specific gene with a putative role in ectodermal patterning. XAG-2 encodes a
      secreted protein, which is expressed in the anterior region of dorsal ectoderm
      from late gastrula stages onwards. Activation of XAG-2 transcription is observed
      in response to organizer-secreted molecules including the noggin, chordin,
      follistatin and cerberus gene products. Overexpression of XAG-2 but not of the
      related cement gland marker XAG-1 induces both cement gland differentiation and
      expression of anterior neural marker genes in the absence of mesoderm formation.
      Further, we show that XAG-2 signaling depends on an intact fibroblast growth
      factor (FGF) signal transduction pathway and that XAG-2-induced anterior neural
      fate of ectodermal cells can be transformed to a more posterior character by
      retinoic acid. Based on these findings we propose a role for XAG-2 in the
      specification of dorsoanterior ectodermal fate, i.e. in the formation of cement
      gland and induction of forebrain fate of Xenopus.

PMID- 9533958
TI  - Proteolytic processing of the Drosophila Spatzle protein by easter generates a
      dimeric NGF-like molecule with ventralising activity.
AB  - Biochemical interactions underlying the generation of the ventralising signal
      during Drosophila embryogenesis were investigated by the expression of
      recombinant Easter and Spatzle proteins. An active form of Easter protease
      cleaves the Spatzle protein, generating a carboxyterminal polypeptide fragment
      which, when microinjected into the perivitelline space of a spatzle deficient
      embryo, directs production of ventrolateral pattern elements. This Spatzle
      carboxyterminal fragment is a disulfide-linked dimer and modelling suggests that
      the core disulfide bonds and dimer arrangement of this fragment are highly
      similar to vertebrate nerve growth factor. Thus Spatzle is a member of a new
      family of neurotrophin-like signalling molecules in invertebrate development.

PMID- 9533959
TI  - Functional analysis of the catalytic subunit of Dictyostelium PKA in vivo.
AB  - The catalytic subunit of the cAMP-dependent protein kinase (PKA) from
      Dictyostelium discoideum contains several domains, including an unusually long N
      terminal extension preceding a highly conserved catalytic core. We transformed
      the aggregationless PkaC-null strain with several deletion constructs of both
      domains. Strains transformed with genes expressing catalytically-inactive
      polypeptides could not rescue development. Cotransformation with constructs
      encoding the N-terminal extension and the catalytic core, both unable to rescue
      development by themselves, yielded transformants able to proceed to late
      development. A 27-amino acid long hydrophobic region, immediately upstream of the
      catalytic core, was found indispensable for PKA function. A putative role of this
      sequence in the acquisition of the active conformation of the protein is
      discussed.

PMID- 9533960
TI  - Chick Delta-1 gene expression and the formation of the feather primordia.
AB  - The chick dermis is known to control the formation of feathers and interfeathery
      skin in a hexagonal pattern. The evidence that the segregation of two types of
      fibroblasts involves Delta/Notch signalling is based on three facts. Rings of C
      Delta-1-expressing fibroblasts precede and delimit the forming feather primordia.
      C-Delta-1 is uniformly expressed in the dermis of the scaleless mutant, which is
      almost entirely devoid of feathers. Feather development is inhibited by
      overexpression of C-Delta-1 in wild type dermis using a retroviral construct. We
      also show that the distribution of C-Delta-1 in the mutant dermis can be rescued
      by its association with a wild type epidermis, which acts as a permissive
      inducer, or by epidermal secreted proteins like FGF2.

PMID- 9533961
TI  - No premature gene expression in germ cells of embryos deriving from nos females.
AB  - The product of nos is required at the posterior pole of the embryo for the
      differentiation of abdominal structures, but not for pole cell formation. A
      previous analysis that reported the expression of germline-specific enhancer-trap
      lines suggested that nos also controls the timing of the initiation of
      transcription of germline-specific genes. Here we repeat the experiments that led
      to this hypothesis and we report further experiments. Our results show that,
      contrary to what had been reported, germ cells of embryos deriving from nos
      females do not show premature gene expression. Germ cells of such embryos,
      however, often show artefactual lacZ staining even in the absence of a lacZ gene.

PMID- 9533962
TI  - Expression of androgen receptor mRNA during mouse embryogenesis.
AB  - Androgen receptor (AR) is a member of the nuclear receptor superfamily which acts
      as a ligand-dependent transcription factor (Beato, M., Herrlich, P., Schutz,
      1989. Steroid hormone receptors: many actors in search of a plot. Cell 83, 851
      857). It plays a pivotal role in sexual development and reproduction (Wilson,
      J.D., Griffin, J.E., George, F.W., Leshin, M., 1981. The role of gonadal steroids
      in sexual differentiation. Rec. Prog. Horm. Res. 37, 1-39; Jost, A., 1990.
      Hormonal control of the masculinization of the body. In: Baulieu, E.E., Kelly,
      D.A., (Eds.), Hormones, from Molecules to Disease. Chapman and Hall, New York and
      London, pp. 439-442.). Mutations in the AR sequence cause a number of
      physiological disorders, such as partial and complete androgen insensitivity
      syndromes, that lead to abnormal sexual development (Patterson, M.N., McPhaul,
      M.J., Hughes, I.A., 1994. Androgen insensitivity syndrome. Balliere's Clin.
      Endocrinol. Metab. 8, 379-404.). There are indications that AR may also have
      other functions. For example, structural alterations of the AR sequence have been
      implicated in prostate cancer (Visakorpi, T., Huytinen, E., Koivisto, P., Tanner,
      M., Keinanen, R., Palmberg, C., Palotie, A., Tammela, T., Isola, J., Kallioniemi,
      O.-P., 1995. In vivo amplification of the androgen receptor gene and progression
      of human prostate cancer. Nature Genet. 9, 401-406.) and in the development of
      spinal and bulbar muscular atrophy, a neurodegenerative disease (Kennedy, W.R.,
      Alter, M., Sung, J.H., 1968. Progressive proximal spinal and bulbar muscular
      atrophy of late onset: a sex-linked recessive trait. Neurology 18, 671-680.).
      Here, we have investigated the spatial and temporal expression of AR during mouse
      organogenesis by in situ hybridisation. We demonstrate that AR transcripts occur
      in the developing external genitalia, pituitary, adrenals, kidneys and musculus
      levator ani, in addition to the known expression sites in the Wolffian ducts and
      its derivatives and during development of the mammary glands.

PMID- 9533963
TI  - Post-embryonic expression pattern of C. elegans let-60 ras reporter constructs.
AB  - let-60 ras plays roles in the differentiation of several C. elegans tissues
      (Yochem, J., Sundaram, M., Han, M., 1997. Ras is required for a limited number of
      cell fates and not for general proliferation in Caenorhabditis elegans. Mol.
      Cell. Biol. 17, 2716-2722). To understand the transcriptional regulation of ras
      and to identify new functions for ras in development, we examined expression
      patterns of let-60::lacZ and let-60::GFP reporter constructs in C. elegans
      hermaphrodites. Fusion constructs were expressed in vulval precursor cells, sex
      myoblasts and in cell lineages of the somatic gonad, germline cells (GFP
      construct only), hypodermis, muscle and nervous system.

PMID- 9533964
TI  - The egghead gene product influences oocyte differentiation by follicle cell-germ
      cell interactions in Drosophila melanogaster.
AB  - Oogenesis in Drosophila is a useful model for studying cell differentiation. We
      have analyzed the role of the egh gene in these processes with the aid of a newly
      isolated viable but female sterile allele. This mutation results in diverse
      variable defects in oogenesis. The most frequent defect being follicles that have
      either more or less than the normal number of 16 germ cells. This is caused by
      erroneous splitting and/or fusion of correct clusters of 16 cystocytes. The
      entire follicle has a rather flexible structure in this allele, most obvious by a
      highly variable position of the oocyte within the follicle. Moreover, a second
      oocyte can also develop in egh clusters. This is exclusively observed in aberrant
      follicles that are generated by the aforementioned splitting/fusion process.
      Surprisingly, even a germ cell which is distinct from the two pro-oocytes can
      differentiate into an oocyte under these circumstances. Hence, determination of
      the oocyte is definitely not fixed when germ cell clusters are enveloped by
      prefollicular cells, and interactions between follicle cells and germ cells must
      play an important role in oocyte specification. Molecular analysis proves that
      the oocyte-specific transcript of the egh gene is drastically reduced in this
      viable allele.

PMID- 9533965
TI  - Personality disorders: psychiatry's stepchildren.

PMID- 9533966
TI  - Suggestions for a framework for an empirically based classification of
      personality disorder.
AB  - BACKGROUND: The classification of personality disorder is one of the least
      satisfactory sections of contemporary psychiatric classification. Fundamental
      problems with current classifications include extensive diagnostic overlap,
      limited evidence of validity, and poor empirical support. METHODS: Conceptual
      analysis and the results of empirical studies are used to propose a framework for
      organizing an empirically based classification. RESULTS: First, personality
      disorder is a form of mental disorder and, therefore, should be classified as a
      single diagnostic entity on Axis I along with other mental disorders. A
      preliminary definition of personality disorder as a tripartite failure involving
      the self system, kinship relationships, and societal relationships is proposed.
      The evidence suggests that this definition can be translated into a reliable set
      of items. Second, the diagnosis of personality disorder should be separated from
      the assessment of clinically relevant personality traits. Given the consistent
      evidential support for a dimensional model of personality disorder, it is
      suggested that personality be coded on a set of trait dimensions selected to
      provide a systematic representation of the domain of behaviours represented by
      current diagnostic concepts. Third, given that personality traits are
      hierarchically organized, it is suggested that an axis for coding personality
      include basic or lower-order dimensions as the primary level of assessment and a
      few higher-order patterns to summarize information for some purposes. CONCLUSION:
      A preliminary list of 16 basic dispositional traits is proposed to describe the
      more specific components of personality disorder based, in part, on the
      convergence of evidence across studies: anxiousness, affective lability,
      callousness, cognitive dysregulation, compulsivity, conduct problems, insecure
      attachment, intimacy avoidance, narcissism, oppositionality, rejection,
      restricted expression, social avoidance, stimulus seeking, submissiveness, and
      suspiciousness. Three higher-order patterns were proposed: emotional
      dysregulation, dissocial behaviour, and inhibitedness, which may occur
      independently or in combination.

PMID- 9533968
TI  - Delusions and self-esteem.
AB  - OBJECTIVE: To investigate the hypothesis that the content of delusions and
      hallucinations is significantly influenced by subjects' global self-esteem and by
      5 specific areas of self-esteem. METHOD: The delusions and hallucinations of 40
      psychotic patients were assessed by 2 independent raters for content indicative
      of positive or negative self-esteem and for the extent to which the delusional
      content would be self-enhancing (or diminishing) and comforting (or
      discomforting) to the subject. These ratings were correlated with the results of
      self-esteem inventories completed by the subjects. RESULTS: The content of
      delusions reflects both global self-esteem and self-regard. CONCLUSIONS: This
      study demonstrates that 2 specific personality factors, global self-esteem and
      self-regard, are reflected in the content of delusions and influence whether
      those delusions are experienced as comfortable (or uncomfortable) and enhancing
      (or diminishing). Delusional content is therefore consistent with patients' views
      of themselves, and this may partially account for the persistence of delusions.

PMID- 9533967
TI  - Does childhood trauma cause personality disorders in adults?
AB  - OBJECTIVE: To examine the relationship between trauma in childhood and
      personality disorders in adulthood. METHOD: A review of the literature was
      conducted. RESULTS: The reported associations between trauma and personality
      pathology are illuminated by the following research findings: 1) personality is
      heritable; 2) only a minority of patients with severe personality disorders
      report childhood trauma; and 3) children are generally resilient, and traumatic
      experiences do not consistently lead to psychopathology. CONCLUSIONS: The role of
      trauma in the personality disorders is best understood in the context of gene
      environment interactions.

PMID- 9533969
TI  - Patients versus rehabilitation practitioners: a comparison of assessments of
      needs for care.
AB  - OBJECTIVE: A group of 47 young adults suffering from schizophrenia was
      interviewed to garner their views on their needs for care. METHOD: Three members
      of a specialized multidisciplinary rehabilitation team, who had been caring for
      these patients, on average, for the past 4 years, completed a questionnaire to
      assess the needs for care of these individuals. Patient and staff assessments
      were then compared. RESULTS: Patients and staff do not share similar views on the
      presence of clinical and social problems. Further analyses of the perceived
      importance of living-skills deficits, the perceived difficulties in dealing with
      these, and the recent developments in rehabilitation practices challenge whether
      patient-staff consensus is indeed essential for rehabilitation. CONCLUSION: We
      propose that staff should listen to patients' points of view more carefully,
      especially in the areas of work, studies, and independent living.

PMID- 9533970
TI  - Creativity and mental illness: is there a link?
AB  - OBJECTIVE: To critically assess the scientific evidence for associating
      creativity with mental illness. METHOD: MEDLINE and secondary literature searches
      identified 29 studies and 34 review articles on creativity and mental illness.
      All studies were critically evaluated. Reviews were also assessed. RESULTS: Of 29
      studies that evaluated possible associations between creativity and mental
      illness, 15 found no evidence to link creativity and mental illness, 9 found
      positive evidence, and 5 had unclear findings. Most studies used flawed
      methodologies with weak (case series or case control) designs. There were no
      randomized or prospective cohort studies. Adequate criteria for determining
      causal association were not met. In 34 selective reviews, despite mixed evidence,
      many authors asserted that creativity and mental illness were positively or
      causally associated. CONCLUSIONS: There is limited scientific evidence to
      associate creativity with mental illness. Despite this, many authors promoted a
      connection. Explanations for this contradiction are explored, and social and
      research implications are discussed.

PMID- 9533971
TI  - Let me count the ways: measuring incidence, prevalence, and impact in
      epidemiological studies.
AB  - This article introduces some of the terms used in psychiatric epidemiology when
      measuring the number of people in a community who have a disorder and the
      possible effects of prevention programs. Incidence is a count of the number of
      new cases of a disorder that occur within a defined time period. It can be
      expressed as either the proportion of people who can be expected to develop the
      disorder within that period (the cumulative incidence) or as the rate per person
      years (the incidence density). Various indices of prevalence refer to the total
      number of people who have the disorder at any one time, whereas indices of risk
      are used to define the probability of developing the disorder. The etiologic
      fraction is the proportion of cases due to a specific cause, and thus it reflects
      the maximum degree to which primary prevention programs can be effective.

PMID- 9533972
TI  - DSM-III-R schizophreniform disorder with good prognostic features: a six-year
      follow-up.
AB  - OBJECTIVE: To determine the outcome of DSM-III-R schizophreniform disorder with
      good prognostic features. METHOD: A 6-year follow-up of 20 cases was conducted
      with structured interviews (comprehensive assessment of symptoms and history) and
      assessments of functioning scales (global assessment of functioning, Strauss
      Carpenter Scale). RESULTS: Thirty-five percent of the cases had major affective
      disorders, 35% had schizophreniform episodes and major affective disorders, 5%
      had schizophreniform episodes only, 10% developed schizophrenia, and 15% had no
      disorders. CONCLUSION: The findings suggest an association between
      schizophreniform disorder with good prognostic features and affective illness.

PMID- 9533973
TI  - Autonomic correlates of antidepressant treatment using heart-rate variability
      analysis.
AB  - OBJECTIVE: To assess the 24-hour temporal-domain heart-rate variability
      correlates of treatment with fluoxetine or doxepin for depression. METHOD: A
      randomized evaluation of fluoxetine and doxepin measured a 50% change in the
      Hamilton Depression Rating Scale (HDRS) score as a response to therapy and was
      correlated with measures of standard deviation of the mean of all 5-minute
      segments of normal electrocardiographic R-R intervals (SDANN), standard deviation
      of all normal R-R intervals (SDNN), root mean square of successive differences in
      R-R intervals (r-MSSD), and percentage difference between adjacent normal R-R
      intervals that are greater than 50 msec (pNN50) from 24-hour electrocardiogram
      (ECG) tapes. RESULTS: Ten out of 14 patients responded. Response was associated
      with an increase in SDANN of 17% (P < 0.05). Nonresponse was associated with a
      17% decrease in SDANN and a 22% decrease in SDNN (both P < 0.05). No other
      measures correlated with therapeutic response. No heart-rate variability (HRV)
      differences between the 2 drug therapies were observed. CONCLUSION: Twenty-four
      hour HRV measures may be useful in assessing response to antidepressant therapy.

PMID- 9533974
TI  - Risperidone-induced delirium.

PMID- 9533975
TI  - Nefazodone withdrawal symptoms.

PMID- 9533976
TI  - Paranoia and agitation associated with olanzapine treatment.

PMID- 9533977
TI  - Management of treatment-resistant schizophrenia with olanzapine.

PMID- 9533978
TI  - Olanzapine and pregnancy.

PMID- 9533979
TI  - Borna disease virus infection and schizophrenia: seroprevalence in schizophrenia
      patients.

PMID- 9533980
TI  - Is there a concentration-effect relationship for sulphonylureas?
AB  - Sulphonylureas have remained the mainstay of oral therapy for type 2 (non-insulin
      dependent) diabetes mellitus (NIDDM). They stimulate insulin release from
      pancreatic beta cells. Pharmacokinetic differences between the various
      sulphonylureas are of clinical importance in terms of the time to onset of
      action, timing of drug administration in relation to food intake, magnitude and
      duration of the glucose-lowering effect and the risk of serious hypoglycaemia.
      Recent studies with improved analytical sensitivity have shown that the
      elimination half-life of glibenclamide is longer than previously thought and that
      2 metabolites of glibenclamide have significant hypoglycaemic activity.
      Furthermore, single dose studies in healthy volunteers using an integrated
      pharmacokinetic-pharmacodynamic model have identified clear concentration-effect
      relationships for both glibenclamide and its metabolites after oral and
      intravenous administration. Under multiple dose conditions, kinetic-dynamic
      relations have been identified with shorter-acting drugs in dosages that give
      discontinuous sulphonylurea exposure. However, at continuous exposure, i.e.
      sustained 24-hour therapeutic concentrations in plasma, there is evidence
      indicating the development of tolerance, which may be caused by downregulation of
      beta cell sensitivity. As more sophisticated concentration-effect studies appear,
      it has become evident that currently recommended maximum daily doses of many
      sulphonylureas are too high.

PMID- 9533981
TI  - Saquinavir. Clinical pharmacology and efficacy.
AB  - Saquinavir is an HIV protease inhibitor with no, or limited, effect on the
      activity of other structurally related human aspartic proteinases. As with other
      HIV protease inhibitors, saquinavir inhibits the cleavage of the gag-pol protein
      substrate leading to the release of structurally defective and functionally
      inactive viral particles. It is active on both HIV-1 and HIV-2, and also has
      activity on chronically infected cells and HIV strains resistant to reverse
      transcriptase inhibitors. Synergy of action has been observed with other
      antiretroviral drugs. Saquinavir is characterised by a low bioavailability which
      is further reduced in the fasting state. Metabolism is mainly hepatic through
      cytochrome P450 (CYP) 3A4, but intestinal metabolism through the same system has
      also been reported. To achieve higher drug plasma concentrations and increase the
      antiviral effect, a new formulation of saquinavir with a higher bioavailability
      has recently been introduced. Higher plasma drug concentrations may also be
      obtained by combining the drug with CYP blockers, such as ritonavir or
      ketoconazole. Because of its metabolic interference with the CYP system,
      saquinavir cannot be coadministered with astemizole, terfenadine or cisapride.
      Rifampicin (rifampin) is also contraindicated because coadministration can lead
      to decreases in saquinavir concentrations. Interactions have also been reported
      with other drugs metabolised through the same system, including non-nucleoside
      reverse transcriptase inhibitors and HIV protease inhibitors. Resistance has been
      observed after both in vitro and in vivo drug exposure, with a relatively
      specific mutation profile compared with other protease inhibitors. Saquinavir is
      generally well tolerated, with mild gastrointestinal symptoms representing the
      most commonly observed adverse effects. Although characterized by low
      bioavailability, in phase III trials saquinavir has been shown to have clinical
      efficacy in terms of survival and progression rate. As with the other protease
      inhibitors, saquinavir should be used in combination with other antiretroviral
      drugs. Current therapeutic guidelines, however, recommend the selection of an
      initial treatment regimen with other protease inhibitors with higher in vivo
      activity in terms of RNA and CD4 response. The results of ongoing studies will
      clarify to what extent a new saquinavir formulation, recently introduced, is
      superior to the previous one in terms of antiviral activity and to provide
      comparisons with other protease inhibitors. Further studies are also needed to
      define the best place of saquinavir within treatment strategies based on protease
      inhibitors, particularly in respect to the optimal sequence for its use with
      other protease inhibitors, and the dynamics of cross-resistance and its role
      within regimens based on the combination of protease inhibitors.

PMID- 9533983
TI  - Drug acetylation in liver disease.
AB  - N-Acetylation is a phase II conjugation reaction mediated in humans by the
      polymorphic N-acetyltransferase 2 (NAT2) and N-acetyltransferase 1 (NAT1).
      Acetylation of some drugs may be modestly decreased in patients with chronic
      liver disease, whereas acute liver injury has no effect on drug acetylation. For
      NAT2 substrates, the impairment in acetylation capacity seems to be phenotype
      specific, with a more prominent effect being exerted in rapid than slow
      acetylators. Thus, in the presence of significant hepatic dysfunction, the
      activity of NAT2 may not exhibit its usual bimodal distribution, and hence
      phenotypic assignment may not be reliable. Furthermore, it remains to be
      evaluated whether the precautions advised for slow acetylators when treated with
      drugs metabolised by NAT2 apply to all patients (regardless of phenotype) with
      liver cirrhosis.

PMID- 9533982
TI  - Physiological changes during the menstrual cycle and their effects on the
      pharmacokinetics and pharmacodynamics of drugs.
AB  - There is an increasing awareness that the exclusion of women from clinical trials
      may lead to inaccurate application of drug therapy in women. Gender and estrus
      cycle differences in the pharmacokinetics and pharmacodynamics of drugs in
      animals have been appreciated for over 60 years, but investigation into these
      differences in humans has only recently occurred. It is postulated that hormonal
      fluctuations within the menstrual cycle phase may be a primary cause of
      documented gender differences in the pharmacokinetics and pharmacodynamics of
      drugs. Existing data suggest that menstrual cycle variations do occur in renal,
      cardiovascular, haematological and immune systems. These physiological changes
      could potentially impact on the pharmacokinetics or pharmacodynamics of drugs by
      altering properties, such as protein binding or the volume of distribution, and
      thereby causing significant effects at various times during the menstrual cycle.
      However, systematic investigations of physiological variability throughout the
      menstrual cycle are limited. Fluctuations in symptom severity and clinical course
      coinciding with the menstrual cycle phase have been seen in some diseases.
      Hormonal fluctuations within the menstrual cycle have been postulated to cause
      disease exacerbation. They may also worsen disease severity by impacting on the
      pharmacokinetics or pharmacodynamics of the medication. Menstrual cycle hormonal
      changes may influence drug absorption, distribution, metabolism or excretion. In
      vivo data to demonstrate an effect of endogenous estrogen or progesterone on
      pharmacokinetics are limited and contradictory. Systematic investigations of
      specific pharmacokinetic and pharmacodynamic changes within the menstrual cycle
      are lacking. Most published studies have been conducted with small numbers of
      women and a limited numbers of menstrual cycle phases within 1 menstrual cycle.
      These design problems have resulted in incomplete data for assessing the effects
      of the menstrual cycle. To date, there are no demonstrated clinically significant
      changes that occur in the absorption, distribution or elimination of drugs. With
      respect to drug metabolism, data are exceedingly sparse and have been collected
      in a suboptimal fashion. Standardisation of study design and analyses in
      systematic investigations of the influence of the menstrual cycle on drug
      pharmacokinetics and pharmacodynamics are needed.

PMID- 9533985
TI  - Febrile seizures: a clinical review.
AB  - Febrile seizures occur in 2 to 5% of children ages three months to five years.
      Evaluation of children with febrile seizures begins with a thorough history and
      physical examination. Therapy and long-term management should focus on treatment
      of the febrile illness and counseling.

PMID- 9533986
TI  - Making sense of musculoskeletal disorders.
AB  - Evaluating musculoskeletal disorders can be challenging and time-consuming.
      Grouping the information from the history and physical examination into broad
      categories, inflammatory vs. non-inflammatory and local vs. systemic, serves as a
      general approach.

PMID- 9533987
TI  - Infection control: past, present, and future issues.
AB  - Primary care providers serve as role models for the prevention of nosocomial
      infections through membership on hospital infection-control committees and daily
      patient care. This article will review five fundamental infection control
      measures: surveillance, isolation, hand washing, disinfection, and sterilization.

PMID- 9533988
TI  - Sexually transmitted diseases.
AB  - Containment of sexually transmitted diseases (STDs) requires that physicians
      become meticulous in prescribing appropriate treatment, and in diagnosis,
      especially those with asymptomatic infection. Physicians must educate their
      patients and community on the acquisition, transmission, and prevention of STDs.

PMID- 9533984
TI  - The relationship between serum concentration and therapeutic effect of
      haloperidol in patients with acute schizophrenia.
AB  - Haloperidol is the most commonly used antipsychotic drug in the therapy of acute
      schizophrenia. Clinicians have been using therapeutic drug monitoring in an
      attempt to improve clinical application of this drug. The scale of interest in
      this area is emphasised by the large number of studies (about 50) concerning the
      serum concentration-therapeutic effect relationship (SCTER) of haloperidol,
      including 35 studies on patients with acute schizophrenia. However, conflicting
      results concerning the existence and position of a therapeutic window have
      emerged. This article aims to provide a comprehensive review of the study design
      of studies in patients with acute schizophrenia before the study data are used
      for decision-making. For this purpose, a reproducible system for the evaluation
      of studies in this special area, a so-called total study score (TSS), was
      developed on an empirical basis. Thus, insufficient study design was found to be
      a reason for negative results. On the other hand, in spite of a great
      variability, the majority of studies with good design provided evidence for a
      significant SCTER: a bisigmoidal dependence of clinical effect on haloperidol
      serum concentration. The therapeutic effects of haloperidol increase at low
      concentrations, and the concentration has a maximum effect at about 10
      micrograms/L and again decreasing at higher concentrations. The data of 552
      patients also fit to this model in a single scatter plot (pseudo-r2 = 0.076, p <
      0.001). The position of the therapeutic window was determined at about 5.6 to
      16.9 micrograms/L. Patients treated with serum concentrations within this optimal
      range had a significantly better response compared with outside this range (p <
      0.001, Student t-test). Therefore, a quantitative synthesis of all available data
      by means of effect-size analysis provides a mean effect-size (g) = 0.499 +/-
      0.182 (standard deviation) for the comparison of haloperidol-treatment with serum
      concentrations within versus outside the therapeutic window. Thus, because of
      this moderate positive effect, serum concentration assay of haloperidol is
      recommended for patients with acute schizophrenia in a therapeutic drug
      monitoring programme. The modalities of haloperidol therapeutic drug monitoring
      in clinical practice are discussed, e.g. patient selection, method and time for
      serum concentration measurement, influence of premedication and comedication,
      interpretation of results and dose adjustment. Clinical investigations into this
      subject should focus on covariates which are responsible for the variability of
      the SCTER. Serum concentration assay is advised for investigations of nonresponse
      to exclude patients with pseudo-drug resistance.

PMID- 9533989
TI  - The burden of physical inactivity & cardiovascular heart disease.
AB  - Heart disease exacts a tremendous toll each year in mortality and health care
      expenditures. Although physical activity reduces the risk of heart disease, the
      population remains inactive. The importance of physical activity in risk and
      health care cost reduction is discussed.

PMID- 9533990
TI  - The role of the primary care physician in caring for patients with type-1
      diabetes.
AB  - The management of type-1 diabetic patients is a challenge. Given the natural
      frequency of this medical problem, most primary care providers will have such
      patients in their office-based practice. The push for tighter control in order to
      lessen long-term complications is a sensible move, but it does not inherently
      require that you absent yourself from the loop. Most of the hoopla from the DCCT
      study has been used to justify the role of the endocrine sub-specialty team in
      the "primary care" management of all diabetic patients so that third-party payers
      will continue to fund such care as routine. While such team management has clear
      benefits, it should not preclude your active involvement in day-to-day management
      for fear that you do not have the proper credentials. Hopefully, this overview
      will give you the confidence to jump back in the ring.

PMID- 9533991
TI  - Retrograde memory deficits in severe closed-head injury patients.
AB  - A battery of tests evaluating different aspects of retrograde memory
      (autobiographical, public events, semantic knowledge) was administered to a group
      of 20 patients who had suffered from a severe closed-head injury (CHI) and who
      had recovered from the post-traumatic amnesia period and to a group of sex-, age-
      and education-matched normal controls. Results document a high prevalence of
      retrograde memory deficits among CHI individuals. The deficit involves both
      autobiographical and public events memories and extends to early acquired basic
      and cultural knowledge. The severity of the deficit does not vary according to
      some kind of temporal gradient or according to a presumed hierarchical or
      modality organization of the semantic system. However, in the domain of basic
      knowledge it more severely affects information pertaining to living than
      nonliving categories of objects. With the exception of a more severe deficit in
      retrieving autobiographical events occurred in the last year before trauma in a
      subgroup of patients with focal lesions restricted to the right hemisphere as
      compared to left lesioned patients, no clear relationship emerges between
      severity of the retrograde memory deficit and locus of focal cerebral lesions as
      demonstrated by neuroradiological exams.

PMID- 9533992
TI  - Recognition memory and memory for order in script-based stories following frontal
      lobe excisions.
AB  - Memory for stories was investigated in 25 patients with frontal lobe excisions
      and 25 control subjects. The subjects were presented with three different story
      types that either conformed to a well-known script, contained the same elements
      as a script but in a randomised order, or described a novel event. Subjects were
      asked to perform a test of recognition memory and memory for order on words
      presented in each story. The frontal lobe patients were unimpaired on the
      recognition memory test for salient words taken from each story. However, an
      impairment was observed in the frontal patients when they were asked to order the
      words taken from the novel story only. This deficit was no longer seen when the
      subjects were required to order sentences describing the key events in the story.
      These findings help to elucidate the role of the frontal lobes in memory for
      order information.

PMID- 9533993
TI  - Disorders of auditory processing: evidence for modularity in audition.
AB  - This article examines four disorders of auditory processing that can result from
      selective brain damage (cortical deafness, pure word deafness, auditory agnosia
      and phonagnosia) in an effort to derive a plausible functional and
      neuroanatomical model of audition. The article begins by identifying three
      possible reasons why models of auditory processing have been slower to emerge
      than models of visual processing: neuroanatomical differences between the visual
      and auditory systems, terminological confusions relating to auditory processing
      disorders, and technical factors that have made auditory stimuli more difficult
      to study than visual stimuli. The four auditory disorders are then reviewed and
      current theories of auditory processing considered. Taken together, these
      disorders suggest a modular architecture analogous to models of visual processing
      that have been derived from studying neurological patients. Ideas for future
      research to test modular theory more fully are presented.

PMID- 9533994
TI  - Effortful echolalia.
AB  - We report three cases of effortful echolalia in patients with cerebral
      infarction. The clinical picture of speech disturbance is associated with Type 1
      Transcortical Motor Aphasia (TCMA, Goldstein, 1915). The patients always spoke
      nonfluently with loss of speech initiative, dysarthria, dysprosody, agrammatism,
      and increased effort and were unable to repeat sentences longer than those
      containing four or six words. In conversation, they first repeated a few words
      spoken to them, and then produced self initiated speech. The initial repetition
      as well as the subsequent self initiated speech, which were realized equally
      laboriously, can be regarded as mitigated echolalia (Pick, 1924). They were
      always aware of their own echolalia and tried to control it without effect. These
      cases demonstrate that neither the ability to repeat nor fluent speech are always
      necessary for echolalia. The possibility that a lesion in the left medial frontal
      lobe, including the supplementary motor area, plays an important role in
      effortful echolalia is discussed.

PMID- 9533995
TI  - Spatio-temporal working memory and frontal lesions in man.
AB  - The delayed-response paradigm is thought to be a marker of the activity of the
      dorsolateral convexity of primates' prefrontal cortex, as this procedure requires
      the activation of working memory processes. Although the role of the dorsolateral
      prefrontal cortex (DLPC) in working memory seems to be well established, much
      remains to be understood about the processes this structure actually controls:
      encoding domain-specific information, its retention in short-term memory, its
      monitoring in working memory, or its selection and retrieval when a specific
      response program is required. To clarify the role of the DLPC in delayed-response
      tasks in humans, a set of sequencing paradigms was designed which incorporates
      the dissociation of (1) spatial and temporal parameters, (2) recall and
      recognition processes, and (3) the presence or absence of a delay. Performance of
      a group of patients with DLPC lesions (n = 8) was compared to that of age-matched
      normal subjects (n = 8). To verify the specificity of the results obtained for
      the DLPC lesioned patients, the performance of patients with a temporal lobotomy
      was also studied (n = 10). A significant effect of the delay was observed only in
      patients with DLPC lesions, affecting both their spatial and spatio-temporal
      recall, whereas their spatio-temporal recognition was normal. These findings
      suggest that the DLPC plays a role in the retrieval of visuospatial information
      for guiding a response program.

PMID- 9533996
TI  - Support for a structural model of aural asymmetries.
AB  - Right ear (RE) advantages for the recognition of speech can be explained by
      structural or attentional mechanisms. Structural mechanisms focus on biases in
      the neural access the ears have to the contralateral and ipsilateral cerebral
      hemispheres. Attentional mechanisms focus on biases in hemispatial attention. The
      contribution of structural and attentional mechanisms for a monaural lexical
      decision task was examined in a group of 26 dextral adults. Trials requiring a
      lexical decision were randomly intermixed with a tone discrimination task. A pre
      test demonstrated that the tone discrimination task produced no ear asymmetry,
      but could be affected by shifts in spatial attention. Responses were faster in
      the RE for the lexical decision task. No asymmetry emerged for the tone
      discrimination task. If the RE advantage for lexical decisions was the result of
      an attentional bias, a RE advantage should have been evident for the tone
      discrimination task. The independence of the two tasks supports a structural
      model of perceptual asymmetry. A structural model which takes into account the
      dynamic functional organization of the hemispheres is proposed.

PMID- 9533997
TI  - Transient retrograde amnesia associated with impaired naming of living
      categories.
AB  - A ease of pure retrograde amnesia following mild head injury is reported. The
      patient, who also showed a deficit in verbal fluency and a living/non-living
      dissociation in naming during the amnesic period, recovered progressively in
      about ten days post-trauma. Both a psychogenic and an organic origin could be
      taken into account. A mechanism (no matter if psychogenic or organic) can be
      hypothesized, which produces a functional inhibition also involving performances
      that are unlikely to be affected by psychological factors.

PMID- 9533998
TI  - Laterality in the use of the prehensile tail in the spider monkey (Ateles
      geoffroyi).
AB  - The purpose of this study was to assess the occurrence of lateral biases in the
      use of the prehensile tail in Ateles geoffroyi. 24 spider monkeys were presented
      with three food-reaching tasks designed to differ in the precision of motor
      control needed for successful food retrieval and assessed for lateral preferences
      in tail use with a minimum of 50 caudal reaches per animal and task. Highly
      lateralized tail use was found in 16 animals, distributed almost equally between
      left- and right-preferent individuals, consistent in strength and direction
      across tasks, and not significantly correlated with manual preferences. Eight
      infant monkeys did not cooperate suggesting an age-dependency in the development
      of tail use skills. The results give evidence of a hitherto undescribed example
      of behavioral asymmetry in a nonhuman primate species which may offer an
      additional approach to the investigation of cortical plasticity and functional
      hemispheric asymmetries.

PMID- 9533999
TI  - Seeing objects smaller than they are: micropsia following right temporo-parietal
      infarction.
AB  - We report the case of an 84-year-old lady who, after a right temporo-parietal
      infarction, complained of seeing things smaller than she expected. She also
      related that straight lines appeared distorted and described seeing colours as if
      they were a badly mixed assemblage of hues. Her visual field was normal except
      for a transient left field extinction. No spatial neglect emerged. The patient's
      micropsia remained unchanged during the course of the six month follow-up.

PMID- 9534000
TI  - Contrast sensitivity loss in the neglected hemifield.
AB  - Contrast sensitivity to gratings of various spatial frequencies displayed in the
      left and right visual hemifield was measured in a group of ten right brain
      damaged patients with unilateral visuospatial neglect. Two groups of ten left
      brain-damaged (LBD) and ten right brain-damaged (RBD) patients without neglect
      served as controls. All patients had normal visual fields according to standard
      clinical procedure. Stimuli were patches of sinusoidal gratings of 1, 2, 4 and 8
      c/deg spatial frequency. The patches subtended 6 deg and were displayed at 3 deg
      of eccentricity. A two-alternative forced-choice technique was employed. Results
      showed a reduction in contrast sensitivity for stimuli presented to the
      contralesional hemifield with respect to the ipsilesional hemifield in patients
      with neglect. No difference in contrast sensitivity between hemifields was found
      for LBD and RBD groups. These findings indicate a basic visual impairment in the
      contralesional hemifield in patients with neglect.

PMID- 9534001
TI  - Ipsilateral neglect: reversal of bias or exaggerated cross-over phenomenon?
AB  - When right brain injury produces contralesional neglect (CN), patients typically
      misbisect lines to the right. However, others demonstrate so-called "ipsilateral
      neglect" (IN) with misbisection to the left of midpoint. Paradoxically, most
      patients with CN also demonstrate a 'cross-over' phenomenon whereby they
      misbisect short lines to the left. It is not known whether patients with IN
      actually have a contralesional bias opposite the ipsilesional bias observed with
      CN, or if their performance reflects an exaggerated cross-over. These
      alternatives can be distinguished by power function analysis which evaluates the
      relationship between magnitude of perception and stimulus magnitude. Using line
      bisection tasks to derive a power function, an IN patient showed a reduced
      exponent (beta = 0.841), falling outside 95% confidence intervals (CI) for
      controls but within the CI for CN patients. The IN patient showed a greatly
      increased constant (K = 7.82), extending outside the CI for both controls and CN
      patients. The results suggest that the anomalous leftward misbisection with IN is
      associated with an exaggerated cross-over point and not simply reversal of
      spatial bias.

PMID- 9534002
TI  - Proper name anomia and anomia for the names of people: functionally dissociable
      impairments?
AB  - This paper reviews the performance of 10 previously reported patients who have
      deficits in recalling the names of people, but whose performance in recalling
      common names is relatively well preserved. An analysis of face naming ability in
      these 10 patients reveals that the proportion of faces that a patient can name is
      closely related to whether or not the patient has a retrieval problem that also
      extends to the recall of other types of proper names such as the names of towns.
      This analysis suggests that names of faces are particularly difficult to recall
      relative to other types of proper names, and provides no support for the view
      that a specialised brain mechanism is involved in the retrieval of people's
      names.

PMID- 9534003
TI  - Reciprocal links between metabolic and ionic events in islet cells. Their
      relevance to the rhythmics of insulin release.
AB  - The notion of reciprocal links between metabolic and ionic events in islet cells
      and the rhythmics of insulin release is based on (i) the rhythmic pattern of
      hormonal release from isolated perfused rat pancreas, which supports the concept
      of an intrapancreatic pacemaker; (ii) the assumption that this phasic pattern is
      due to the integration of secretory activity in distinct functional units, e.g.
      distinct islets; and (iii) the fact that reciprocal coupling between metabolic
      and ionic events is operative in the secretory sequence.

PMID- 9534004
TI  - Role of mitochondrial calcium in metabolism-secretion coupling in nutrient
      stimulated insulin release.
AB  - Glucose-stimulated insulin release from pancreatic beta cells involves a complex
      series of signalling pathways. In many forms of diabetes, lesions in this process
      cause or aggravate the diabetic phenotype. A common motif in these cascades is
      the elevation of intracellular Ca2+ both in the cytosolic compartment ([Ca2+]c)
      and within the mitochondria ([Ca2+]m). These parameters can be effectively
      monitored using the photoprotein aequorin which can be targeted to subcellular
      compartments by transfection. It is shown that physiological concentrations of
      glucose elicit [Ca2+]c oscillations measured with fura-2, which correlate well
      with oscillatory NAD(P)H fluorescence in the mitochondria. Aequorin measurements
      of [Ca2+]m, though unable to detect oscillations on a single cell basis, reveal
      large increases in intraorganellar [Ca2+] in response to glucose, elevated amino
      acid levels and depolarizing concentrations of KCI. These oscillations, in turn,
      mirror changes in the insulin secretion profile. Since several of the key
      mitochondrial dehydrogenases involved in oxidative phosphorylation are
      exquisitely sensitive to changes in [Ca2+], it is proposed that alterations in
      [Ca2+]m lead to increased activity of the tricarboxylic acid cycle and subsequent
      ATP production, thereby facilitating exocytosis of insulin from secretory
      granules. The involvement of the mitochondria in these processes is examined, as
      is the putative role of efficient mitochondrial genome transcription and
      translation in normal and diabetic states.

PMID- 9534005
TI  - Generation of glucose-dependent slow oscillations of cytoplasmic Ca2+ in
      individual pancreatic beta cells.
AB  - Individual pancreatic beta cells respond to glucose stimulation with large
      amplitude (300-500 nM) oscillations in the cytoplasmic Ca2+ concentration
      ([Ca2+]i). These oscillations (frequency 0.05-0.5/min) depend on rhythmical
      depolarization of the plasma membrane, with influx of Ca2+ through voltage
      operated channels, but do not require intracellular mobilization of Ca2+. Patch
      clamp analyses of the activity of ATP-sensitive K+ channels indicate that
      oscillations in beta-cell metabolism underlie the rhythmical depolarizations,
      causing the large amplitude oscillations of [Ca2+]. The oscillatory responses of
      adjacent beta cells are synchronized by gap-junctional coupling in cellular
      microdomains. With increasing glucose concentration, previously unresponsive
      domains are activated, and their oscillations entrained with those of other
      active domains. In pancreatic islets, glucose-induced large amplitude
      oscillations occur in parallel with insulin release pulses, the amplitudes of
      which are determined by the number of beta cells recruited into the secretory
      state.

PMID- 9534006
TI  - Functional significance of Ca2+ oscillations in pancreatic beta cells.
AB  - Several aspects of pancreatic beta cell function display marked oscillations even
      during continuous stimulation with a stable glucose concentration. This review
      article focuses on the characteristics, mechanisms and potential roles of the
      oscillations of cytoplasmic Ca2+ concentration [(Ca2+]i) in beta cells. These
      oscillations result from an intermittent influx of Ca2+ through voltage-dependent
      Ca2+ channels activated by periodic depolarizations of the plasma membrane. In
      each islet, [Ca2+]i oscillations are synchronous in all beta cells and trigger
      similar oscillations of insulin secretion. Changes in [Ca2+]i are thought to play
      a minute-to-minute regulatory role in secretion, but the effectiveness of Ca2+ on
      the secretory process is markedly influenced by various amplification mechanisms.
      It is still unclear whether the oscillations of [Ca2+]i reflect functional
      advantages for the beta cell itself or are simply necessary to ensure
      oscillations of plasma insulin levels through pulsatile secretion of the hormone.

PMID- 9534007
TI  - Cytosolic calcium oscillations and insulin release in pancreatic islets of
      Langerhans.
AB  - Stimulation of insulin release by glucose and other nutrients has been attributed
      to a rise of cytoplasmic Ca2+([Ca2+]i). In intact pancreatic islets, this rise is
      organized in oscillations. Two types of [Ca2+]i oscillations are mainly detected.
      Fast oscillations (frequency of approximately equal to 3 min-1) are consistently
      observed, and their duration depends on glucose concentration. They are due to a
      bursting of electrical activity and occur synchronously throughout the islet.
      Slow oscillations (frequency of 0.2 min-1) also appear in response to other
      nutrient secretagogues (ketoisocaproate, leucine, isoleucine). They most probably
      constitute the physiological oscillatory pattern because islets perifused with a
      solution containing a mixture of amino acids and glucose at concentrations found
      in the plasma of fed animals showed the same oscillatory pattern. Slow [Ca2+]i
      oscillations may constitute the framework for pulsatile insulin release observed
      in vivo.

PMID- 9534008
TI  - Pulsatile insulin release: role of cytoplasmic Ca2+ oscillations.
AB  - Oscillations of plasma insulin are essential for the hypoglycaemic effect of the
      hormone. Disturbance and partial loss of these oscillations occur during the
      development of Type 2 diabetes, in association with down-regulation of insulin
      receptors and insulin resistance. Oscillations with a frequency similar to that
      of plasma insulin have been observed in the cytoplasmic Ca2+ concentration
      ([Ca2+]i) of pancreatic beta cells, indicating that the ion plays a role in
      generating insulin pulses. Studies of individual islets have revealed that
      oscillations of [Ca2+]i and insulin release are synchronous. However, insulin
      release is also pulsatile under conditions in which [Ca2+]i is stable. These
      results support the notion that variations in the ATP/ADP ratio are sufficient to
      induce pulsatile insulin release. Under physiological conditions, this
      pulsatility may depend on the synergistic effects of ATP/ADP and [Ca2+]i
      oscillations.

PMID- 9534009
TI  - Hormonal counterregulation failure in rats is related to previous hyperglycaemia
      hyperinsulinaemia.
AB  - Hyperglycaemia and hyperinsulinaemia were induced in rats by a continuous 48-h
      infusion with glucose. Discontinuation of glucose infusion resulted in marked,
      persistent hypoglycaemia. To further delineate the mechanism underlying this
      condition, we measured counterregulatory hormone levels, in vivo glucose kinetics
      (glucose production = rate of appearance = Ra; glucose utilization = rate of
      disappearance = Rd), and in vitro gluconeogenesis during the 48-h postinfusion
      period. Prior to cessation of glucose infusion, Rd was increased 6-fold when
      compared to control rats, whereas Ra was totally abolished. During the first hour
      after the end of glucose infusion, Ra increased and Rd decreased (but was still
      higher than Ra), inducing hypoglycaemia which stabilized after 1 h at ??126??3.5
      mmol/l when both Ra and Rd became equal. Despite hypoglycaemia, plasma glucagon
      and catecholamine levels did not increase during the 3-to 36-h time interval. The
      increase in Ra during the first hour post-infusion was not related to changes in
      counterregulatory hormone response. The increase in glucose production was
      accounted for by glycogenolysis, as shown by total depletion in liver glycogen
      within 6 h and thereafter by gluconeogenesis. In vitro experiments using isolated
      hepatocytes suggested that gluconeogenesis was supported during the first 24 h by
      substrates entering the pathway beyond the step catalysed by the PEPCK enzyme.
      Thereafter, lactate became the major substrate, and this condition was associated
      with a progressive rise in glucagon concentration. It is concluded that 48 h of
      hyperglycaemia/hyperinsulinaemia resulted in a failure of counterregulatory
      hormonal response to hypoglycaemia. Yet, despite this lack of counterregulatory
      response, hepatic gluconeogenesis was stimulated in response to hypoglycaemia.

PMID- 9534010
TI  - Added benfluorex in obese insulin-requiring type 2 diabetes.
AB  - To determine the effect of benfluorex on glycaemic control in obese insulin
      requiring Type 2 diabetes, 76 patients (aged 53.8 +/- 12.8 years) receiving
      insulin (> or = 0.5 IU/kg) and an appropriate low-calorie diet were evaluated
      after a 1-month run-in followed by a 3-month double-blind treatment period (3
      tablets daily) with benfluorex (B; n = 37) vs placebo (P; n = 39). At inclusion,
      the B and P groups respectively did not differ in body weight (80.9 +/- 10.3 vs
      77.2 +/- 9.1 kg), body mass index (BMI) (30.1 +/- 4.6 vs 29.0 +/- 2.3 kg/m2) or
      fasting blood glucose (11.22 +/- 4.33 vs 10.35 +/- 4.42 mmol/l). However, daily
      insulin dose and HbA1c levels were higher in the B group (59.9 +/- 18.6 vs 50.4
      +/- 12.8 IU, p = 0.012; and 7.72 +/- 1.60 vs 6.96 +/- 1.27%, p = 0.025,
      respectively). After 3 months of treatment, the decrease in daily insulin dose
      was greater in the B group (8.7 +/- 10.1 vs 2.7 +/- 8.1 IU; p = 0.032), with a
      decrease in HbA1c (-0.73 +/- 1.74%, p = 0.026), vs no change in the P group
      (+0.01 +/- 1.65%, NS) and a tendency towards a greater decrease in fasting blood
      glucose (-1.43 +/- 5.41 vs +0.42 +/- 3.78 mmol/l respectively). Body weight and
      BMI were also lower in the B group (1.77 n 2.27 vs 0.21 n 2.68 kg, p = 0.013; and
      0.64 +/- 0.84 vs 0.07 +/- 1.07 kg/m2, p = 0.019, respectively) in parallel with
      the decrease in insulin dose. Triglycerides decreased in the B group vs an
      increase in the P group (-0.54 +/- 2.04 vs +0.21 +/- 0.70 mmol/l p = 0.06). Total
      cholesterol decreased within the B group (-0.47 +/- 1.01 mmol/l; p = 0.013) and
      vs the P group (intergroup p = 0.006). Adverse events were reported in 11
      patients in the B group vs 5 in the P group (NS), causing dropout in only one
      case (intercurrent illness, P group). Addition of benfluorex in obese insulin
      requiring Type 2 diabetes thus enhances glycaemic control and lowers both daily
      insulin requirement and body weight. Benfluorex + insulin is a valid alternative
      for obese patients who remain poorly controlled despite insulin or who require
      high doses of insulin.

PMID- 9534012
TI  - Evaluation of the DCA 2000 system for glycated haemoglobin measurement.

PMID- 9534011
TI  - Erythropoietin can deteriorate glucose control in uraemic non-insulin-dependent
      diabetic patients.
AB  - Two patients with non-insulin-dependent diabetes mellitus (NIDDM) and moderate
      chronic renal failure experienced a worsening of glycaemic control when
      recombinant human erythropoietin (r-HuEPO) was introduced, leading to insulin
      therapy. A 71-year-old woman with a 20-year history of NIDDM had presented
      histologically documented diabetic nephropathy for 2 years during which glucose
      control was stabilized by a diet and glibenclamide 10 mg. In the 6 months
      following introduction of r-HuEPO, hyperglycaemic symptoms developed, and HbA1C
      increased from 8.9% to 12.3%. During this period, no intercurrent events
      occurred, except epistaxis due to accelerated hypertension one month after r
      HuEPO was started. A 62-year-old man had a 15-year history of NIDDM, with
      proliferative retinopathy, macroproteinuria and chronic renal failure for 4
      years. The day after the first injection of r-HuEPO, capillary glucose level rose
      dramatically. In both of these cases, antihypertensive treatment was increased
      and insulin introduced. The role of r-HuEPO in hyperglycaemia was probable in the
      first case and highly probable in the second. Reports about the effects of r
      HuEPO on glucose metabolism in uraemic patients are conflicting. Short- and long
      term effects can differ, although long-term benefit is likely. The fact that our
      patients were not dialized may have been important. Clinicians should be aware
      that glucose control may deteriorate with r-HuEPO, requiring some uraemic NIDDM
      patients to undergo insulin therapy.

PMID- 9534014
TI  - [Revision of diagnostic criteria of diabetes. The reasons and the consequences].

PMID- 9534013
TI  - Normal blood-glucose concentration which range for what?
AB  - Two definitions of normality ("isolated" or "correlated") are considered. The
      boundaries of "isolated" normality were determined by a statistical procedure,
      whereas the "correlated" approach was related to a clinical or predictive
      definition. In the latter case, the biological variations were considered
      abnormal if they implied a hazard with some significant future ailment as a risk
      factor. In this pragmatic approach, the upper limit of normal/abnormal variations
      is the point beyond which medical strategy is related to the most expected
      benefit when applied to a definite population or to an individual patient. The
      capacity of a diagnostic test to discriminate between patients with a defined
      risk and those without risk depends strictly on the value of the parameter
      chosen. In medical care for the prevention of vascular complications in diabetic
      patients or with foetal risks in pregnant women, the limits of the so-called
      normal range of glycaemia and other parameters should be determined according to
      the objective of the preventive and/or therapeutic measures to be prescribed.

PMID- 9534015
TI  - [Escaping oral hypoglycemic agents in type 2 diabetes: importance and limitations
      of transitory optimized insulin therapy].

PMID- 9534016
TI  - [Hormonal contraception in the diabetic woman].

PMID- 9534017
TI  - [Nutrition and insulin resistance in the non-insulin-dependent diabetic].

PMID- 9534018
TI  - Should antioxidant vitamins be routinely recommended for older people?
AB  - The hypothesis that oxidative damage due to free radicals is an important cause
      of aging is the subject of much research and even more interest among the public
      and lay media. An increasing number of older people are asking whether they
      should be taking antioxidant vitamins, despite their considerable cost.
      Epidemiological and laboratory evidence indicates that oxidative damage caused by
      oxygen free radicals is important in many of the major diseases of older age. It
      is also clear that a diet high in antioxidants protects against these diseases,
      including many cancers and ischaemic heart disease. However, it has not been
      proven whether antioxidant vitamins, taken as dietary supplements, provide the
      same level of protection as a diet that is rich in fruit and vegetables. Although
      there appears to be no reason to discourage older people from taking vitamin E
      (tocopherols) and ascorbic acid (vitamin C), the best advice to give them is to
      reduce their intake of xenobiotics, to drink tea instead of coffee, and to eat
      liberal amounts of fruit, vegetables, nuts, soya beans and lentils. The use of
      beta-carotene as a dietary supplement should be discouraged.

PMID- 9534019
TI  - Recognition and treatment of psoriasis. Special considerations in elderly
      patients.
AB  - Psoriasis is a chronic dermatological disorder that affects 1 to 2% of the
      general population. Although its aetiology is still unknown, the importance of
      genetic factors has been confirmed by many studies, mainly in young individuals.
      With respect to clinical features, plaque-type psoriasis (localised or
      generalised) is the most common form. At present, there is no cure for psoriasis
      and the available treatments can only temporarily clear the skin manifestations.
      The choice of treatment regimen for psoriasis is based on the severity of the
      disease, the patient's gender, age, treatment history and level of compliance,
      and the physician's personal experience. All therapies for psoriasis have
      different and potentially toxic effects. Therefore, a good knowledge of their
      relative and absolute contraindications, adverse effects and interactions with
      other drugs is mandatory. The elderly represent a significant proportion of
      patients with psoriasis because its prevalence increases with age. Physicians,
      particularly general practitioners, dermatologists and gerontologists, must be
      aware of the problems that the treatment of psoriasis in the elderly can present.
      This is especially important because of the increased risk of adverse drug
      reactions in the elderly.

PMID- 9534020
TI  - Calcium sensitising agents in heart failure.
AB  - Congestive heart failure (CHF) is a common cardiovascular disorder that is
      characterised, in part, by a decreased cardiac output reserve. Accordingly, there
      is ongoing interest in the role of positive inotropic agents (e.g. adrenergic
      agonists and phosphodiesterase type III inhibitors, which mediate their
      cardiovascular effects via a cyclic adenosine monophosphate-dependent mechanism)
      in the treatment of CHF. However, enthusiasm for positive inotropic therapy in
      CHF has been dampened by the results of clinical trials, which have shown that
      these drugs are associated with an increased risk of mortality. Calcium
      sensitising agents are a heterogeneous group of positive inotropic agents that
      mediate their cardiovascular actions (at least in part) by increasing the
      sensitivity of the contractile elements to calcium. Increased sensitivity to
      calcium may be related to changes in calcium binding to troponin C, or to direct
      effects on the actin-myosin complex. In addition, the inhibition of
      phosphodiesterase type III may contribute to the positive inotropic action of
      calcium sensitising agents. Five agents with calcium sensitising properties
      (pimobendan, levosimendan, MCI-154, EMD-53998 and CGP-48506) have been studied as
      possible therapies for CHF. All of these agents have demonstrated a positive
      inotropic action in isolated cardiac tissue and in animal models of CHF. In
      clinical trials, pimobendan, the most extensively studied of these drugs, was
      well tolerated and was associated with improved exercise tolerance during the
      first 6 months of therapy; however, it was also associated with a nonsignificant
      trend towards increased mortality. Because many of the calcium sensitising agents
      also inhibit phosphodiesterase type III activity, the long term safety of these
      agents is uncertain. Large-scale survival trials are required to determine the
      long term safety and efficacy of these agents before their role in the treatment
      of CHF can be defined.

PMID- 9534022
TI  - Brimonidine. A review of its pharmacological properties and clinical potential in
      the management of open-angle glaucoma and ocular hypertension.
AB  - Brimonidine is a highly selective alpha 2-adrenoceptor agonist which reduces
      intraocular pressure (IOP) by reducing aqueous humour production and increasing
      aqueous humour outflow via the uveoscleral pathway. Brimonidine is indicated for
      the topical management of open-angle glaucoma or ocular hypertension. In 3 large
      comparative studies in patients with open-angle glaucoma or ocular hypertension,
      the ocular hypotensive efficacy of brimonidine was maintained during treatment
      periods of up to 1 year. Mean reductions in peak (measured 2 hours after the
      morning dose) and trough (measured 12 hours after the evening dose) IOP were 5.6
      to 5.9 and 3.3 to 3.7 mm Hg, respectively, after 3 or 12 months of treatment with
      brimonidine 0.2% twice daily. The efficacy of brimonidine in this setting was
      similar to that of timolol 0.5% twice daily at peak only (-6.0mm Hg), and
      superior to that of betaxolol 0.25% twice daily at both peak (-3.5mm Hg) and
      trough (-2.7mm Hg). When added to topical beta-adrenoceptor antagonist therapy,
      initial results showed brimonidine 0.2% twice daily to have additive ocular
      hypotensive efficacy similar to that of pilocarpine 2% 3 times daily. Thus,
      brimonidine 0.2% may be a useful adjunct in this setting. According to combined
      data from 2 large comparative studies, the most frequent adverse events
      associated with brimonidine therapy were oral dryness (30.0% of patients), ocular
      hyperaemia (26.3%) and ocular burning and/or stinging (24.0%). Ocular allergic
      reactions including allergic blepharitis, blepharoconjunctivitis and follicular
      conjunctivitis occurred with an incidence of 9.6% in 1 study. In a third
      comparative study, the incidence of adverse events associated with brimonidine
      therapy was lower, with conjunctival hyperaemia (11.4%) the most frequently
      reported event. Changes in systolic and diastolic blood pressure and, to a lesser
      extent, heart rate have been reported in patients treated with therapeutic doses
      of topical brimonidine for up to 12 months, but these changes were not clinically
      significant. Unlike beta-adrenoceptor antagonists, brimonidine is not
      contraindicated in patients with cardiopulmonary disease, although it should be
      used with caution in individuals with severe cardiovascular disease. Thus,
      further studies are warranted to determine the efficacy of brimonidine when used
      in combination with other glaucoma medications and its efficacy relative to newer
      drugs such as dorzolamide and latanoprost. However, available data suggest that
      brimonidine is a promising alternative option for the lowering of IOP in the
      management of open-angle glaucoma and ocular hypertension, particularly in
      patients with cardiopulmonary disease in whom topical beta-adrenoceptor
      antagonist therapy is contraindicated.

PMID- 9534023
TI  - Propionyl-L-carnitine.
AB  - Propionyl-L-carnitine stimulates energy production in ischaemic muscles by
      increasing citric acid cycle flux and stimulating pyruvate dehydrogenase
      activity. The free radical scavenging activity of the drug may also be
      beneficial. Propionyl-L-carnitine improves coagulative fibrinolytic homeostasis
      in vasal endothelium and positively affects blood viscosity. Improvements in
      maximum walking distance (MWD) correlated positively with increased mitochondrial
      oxidative adenosine triphosphate (ATP) synthesis in a study in patients with
      peripheral arterial disease. Oral propionyl-L-carnitine 1 to 3 g/day
      significantly improved mean MWD compared with placebo in patients with peripheral
      arterial obstructive disease (Fontaine Leriche stage II) in double-blind
      multicentre phase III studies (mean improvements ranged from 21 to 50% with
      placebo and from 33 to 73% with propionyl-L-carnitine). In one phase III study,
      propionyl-L-carnitine 1 to 3 g/day significantly improved mean MWD (measured by
      treadmill) compared with placebo (by 73 vs 46% after 24 weeks) in patients with
      intermittent claudication. Oral propionyl-L-carnitine therapy was associated with
      significant improvements in quality of life compared with placebo in patients
      with a baseline MWD < 250m. Propionyl-L-carnitine appears to be well tolerated,
      showing a similar incidence of adverse events to that reported in placebo
      recipients.

PMID- 9534024
TI  - Mechanisms of thyroid hormone action. Implications for the clinical manifestation
      of thyrotoxicosis.
AB  - Serum thyroid hormone concentrations alone do not explain the variability and
      severity of the range of symptoms observed in thyrotoxic patients. Despite gaps
      in our understanding of the links between the clinical manifestations of
      thyrotoxicosis and the underlying mechanisms, much has been learned. A limited
      number of markers directly reflect T3 action. The future elucidation of T3
      targets that mediate these effects should ultimately lead to additional clinical
      markers of tissue-specific T3 action. The availability of such tests should allow
      for more specific treatment of individual patients.

PMID- 9534025
TI  - Clinical and laboratory diagnosis of thyrotoxicosis.

PMID- 9534026
TI  - Subclinical thyrotoxicosis.
AB  - Subclinical thyrotoxicosis is defined as low serum thyrotropin (TSH) and normal
      serum thyroid hormone concentrations. It must be distinguished from nonthyroidal
      illness and secondary hypothyroidism. The most common causes are excessive
      thyroid hormone therapy, autonomously functioning thyroid adenoma, multinodular
      goiter, and Graves' disease, but many patients have no evident thyroid disease. A
      few patients have minor symptoms and signs of hyperthyroidism. The likelihood of
      progression to overt thyrotoxicosis is low, and many patients have normal serum
      TSH concentrations weeks or months later. Treatment should be based on
      consideration of the cause of the subclinical thyrotoxicosis, and whether the
      patient has any clinical manifestations of thyroid hormone excess or underlying
      problems likely to be aggravated by small increases in thyroid secretion.

PMID- 9534021
TI  - Assessment and treatment of bipolar disorder in the elderly.
AB  - The aetiology of late-onset bipolar disorder is heterogeneous because the disease
      is more likely to have a secondary (i.e. a medical disorder or medication
      induced) cause in older than in younger patients. Elderly patients with bipolar
      disorder typically require lithium dosages that are 25 to 50% lower than those
      used in younger individuals. Information on the use of valproic acid (sodium
      valproate) in elderly patients with bipolar disorder is limited but encouraging.
      In contrast, there is virtually no information regarding the use of carbamazepine
      or other drugs in this patient group. Electroconvulsive therapy is well tolerated
      by older people and can be useful for these patients.

PMID- 9534027
TI  - Thyrotoxicosis and the heart.
AB  - This review examines the molecular mechanisms by which thyroid hormone affects
      the cardiovascular system in naturally occurring thyroid disease states. The
      potential utility of thyroid hormone therapy in the management of patients with
      various forms of cardiovascular disease is also discussed.

PMID- 9534028
TI  - Theories of causation of Graves' disease. A historical perspective.
AB  - There have been many theories regarding the origin or etiology of the peculiar
      disorder Robert James Graves first described in 1834. This article is a
      chronological discussion of the main ideas and the eras in which they were
      prominent, including the cardiac, neural, thyroid, pituitary, and modern eras.

PMID- 9534029
TI  - The pathogenesis of Graves' disease.
AB  - Graves' disease, one of the autoimmune thyroid diseases, is caused by the
      production of IgG autoantibodies directed against the thyrotropin receptor. These
      antibodies bind to and activate the receptor, causing the autonomous production
      of thyroid hormones. Despite recent improvements in our understanding of the
      cellular and molecular basis of autoimmunity, our currently available treatments
      for Graves' disease have remained largely unchanged over the last 50 years.
      Nevertheless, new concepts in immune system regulation hold out the prospect in
      the future for intervention designed to modify, and possibly cure, the underlying
      disease process.

PMID- 9534030
TI  - Ophthalmologic aspects of thyroid-related orbitopathy.
AB  - This article explores many of the ophthalmologic aspects of thyroid-related
      orbitopathy. The eight main areas of clinical concern--ocular comfort, optic
      nerve function, exophthalmos, eyelid position, diplopia, cosmesis, soft-tissue
      signs, and psychologic factors--are discussed so that practitioners may be more
      secure in dealing with these areas and in helping patients to be more comfortable
      both physically and psychologically.

PMID- 9534031
TI  - Support groups for patients with Graves' disease and other thyroid conditions.
AB  - Thyroid foundations and associations provide free information and support for
      thyroid patients in countries throughout the world. Their efforts save physicians
      time and increase patient understanding and compliance while reducing anxiety.
      Personal responsiveness to a patient's concerns is important but costly.
      Physicians can help by referring patients to local groups, accepting patient
      referrals from these organizations, and encouraging thyroid patients and
      organizations to help with financial support.

PMID- 9534033
TI  - Hyperthyroidism in pregnancy.
AB  - Hyperthyroidism is second to diabetes mellitus as the most common endocrinopathy
      in pregnancy. Inappropriate secretion of hCG is the most common cause of
      hyperthyroidism in the first part of gestation. In addition to hydatidiform mole
      and hyperemesis gravidarum, nonpathologic-conditions including multiple
      gestation, mild nausea and vomiting, and even normal pregnancies may present with
      transient undetectable or suppressed serum TSH values. The syndrome of transient
      hyperthyroidism of hyperemesis gravidarum is defined as severe nausea and
      vomiting, dehydration, ketonuria, and weight loss of more than 5% by 6 to 9 weeks
      of pregnancy. Thyroid tests are in the hyperthyroid range, and the abnormalities
      are related to the severity of symptoms. Tests normalize with resolution of the
      vomiting, and ATD therapy is not indicated. The natural history of Graves'
      disease in pregnancy is characterized by aggravation in the first trimester,
      amelioration in the second half, and recurrence in the year following delivery.
      ATD treatment is the therapy of choice in pregnancy. Either PTU or MMI may be
      used; the goal is to keep the FT4I in the upper limits of normal with the minimum
      dose of ATD. In approximately 30% of patients, ATDs may be discontinued in the
      last few weeks of gestation. Maternal, fetal, and neonatal complications are
      frequent when hyperthyroidism is not under control. Postpartum hyperthyroidism
      may be caused by an episode of silent thyroiditis or Graves' disease.

PMID- 9534032
TI  - Thyrotoxicosis in children.
AB  - Graves' disease is the predominant cause of hyperthyroidism in the pediatric age
      group. Other disorders must be recognized, however, because adequate management
      relies on a precise diagnosis. Careful monitoring of the thyroid status is
      required during this active phase of growth and development.

PMID- 9534034
TI  - Toxic nodular goiter. Toxic adenoma and toxic multinodular goiter.
AB  - Solitary toxic adenoma and toxic multinodular goiter are very common forms of
      thyrotoxicosis around the world. Advances in molecular biology and genetics have
      led to new insights into the pathogenesis of these disorders. Current theories on
      autonomy in the thyroid are discussed in this article. The therapeutic roles of
      surgery, radioiodine ablation, and percutaneous ethanol administration also are
      reviewed.

PMID- 9534035
TI  - Syndromes of thyrotoxicosis with low radioactive iodine uptake.
AB  - It is very important to diagnose correctly the etiology of thyrotoxicosis,
      because the course and treatment of thyrotoxicosis with low radioactive iodine
      uptake differ significantly from that of hyperthyroidism due to Graves' disease
      or toxic nodular goiter. Many causes of subacute thyroiditis have been identified
      producing a characteristic course of transient hyperthyroidism, followed by
      hypothyroidism, and usually recovery. Ectopic hyperthyroidism includes factitious
      thyroid hormone ingestion, struma ovarii, and, rarely, large deposits of
      functioning thyroid cancer metastases. Iodine-induced hyperthyroidism may be
      associated with low radioiodine uptakes. Amiodarone-associated hyperthyroidism
      may be the result of subacute thyroiditis or iodine-induced hyperthyroidism;
      assessment and treatment can be quite challenging.

PMID- 9534036
TI  - Central hyperthyroidism.
AB  - Central hyperthyroidism is a rare condition in which thyrotoxicosis results from
      primary overproduction of TSH by the pituitary gland with subsequent thyroid
      enlargement and hyperfunction. The two known causes of central hyperthyroidism
      are TSH-producing pituitary tumors (TSHomas) and the syndrome of PRTH. Both of
      these entities are characterized by clinical thyrotoxicosis, diffuse goiters,
      elevated circulating levels of free T4 and T3, and a nonsuppressed serum TSH. It
      is critical to distinguish central hyperthyroidism from the much more common
      types of primary hyperthyroidism, all of which have undetectable TSH values.
      TSHomas and PRTH can usually be differentiated from one another by measuring the
      serum alpha-subunit and the TSH response to intravenous TRH or exogenous thyroid
      hormone, and by pituitary imaging studies. TSHomas are usually benign adenomas
      arising from the monoclonal expansion of neoplastic thyrotropes. Causative
      oncogenes have not yet been convincingly identified. PRTH is a nonneoplastic
      disorder caused by inherited mutations in the gene for the thyroid hormone
      receptor beta; it is a poorly understood variant of GRTH. For unclear reasons, in
      PRTH, the pituitary gland is resistant to the feedback inhibitory effects of
      circulating thyroid hormones while peripheral tissues respond normally, causing
      patients to experience the toxic peripheral effects of thyroid hormone excess.
      TSHomas are best treated by transphenoidal surgical removal. Radiotherapy is
      indicated for inoperable or incompletely resected tumors. Octreotide
      administration is a useful adjunct for preoperatively reducing tumor size and for
      the medical management of surgical treatment failures. PRTH is ideally treated by
      chronically suppressing TSH secretion with medications such as D-thyroxine,
      TRIAC, octreotide, or bromocriptine. If such therapy is ineffective or
      unavailable, thyroid ablation with radioiodine or surgery may be employed with
      subsequent close monitoring of both thyroid hormone status and pituitary gland
      size.

PMID- 9534037
TI  - Treatment of hyperthyroidism with radioactive iodine.
AB  - Treatment of hyperthyroidism with RAI has been performed for more than a half
      century with efficacy and safety. For its optimal use, the physician must employ
      appropriate patient selection criteria and clinical judgment concerning
      pretreatment patient preparation. The dose of the 131I needed remains an area of
      uncertainty and debate; thus far, it has not been possible to resolve the trade
      off between efficient definitive cure of hyperthyroidism and the high incidence
      of post-therapy hypothyroidism. Early side effects are uncommon and readily
      manageable. Other than the need for long-term monitoring and, in most cases,
      lifelong L-T4 treatment, late adverse consequences of this treatment remain only
      conjectural. The available follow-up studies support the current majority opinion
      of North American thyroid specialists that RAI treatment is an excellent choice
      for most hyperthyroid patients.

PMID- 9534038
TI  - Antithyroid drugs for the treatment of hyperthyroidism caused by Graves' disease.
AB  - Therapy for Graves' disease is not straightforward and often involves complex
      decision making. Long-term antithyroid drug therapy is appealing because it is
      nonablative, but it is not for everyone. The physician must weigh the advantages
      and disadvantages of antithyroid drug treatment and help the patient arrive at an
      individualized therapeutic strategy that is appropriate and cost-effective.

PMID- 9534039
TI  - HLA-DQA, -DQB and -DRB allele contribution to narcolepsy susceptibility.
AB  - The association of narcolepsy with HLA class I antigens and HLA class II alleles
      was studies in a series of Spanish narcoleptic patients. The haplotype DRB1*1501
      DRB5*0101-DQA1*0102-DQB1*0602 was found to be significantly associated with the
      disease, while the haplotype DRB1*0701-DRB4*01-DQA1*0201-DQB1*02 might confer a
      slight protective effect against narcolepsy. Gene dose-effect was not seen in any
      of the involved alleles, and linkage disequilibrium between the positively
      associated alleles was found to be stronger in patients than in controls.
      Statistical analysis applied to identify the HLA allele truly responsible for the
      association did not clearly discriminate between the contribution of DRB1*1501
      and that of DQB1*0602, but it proved that the association with DQA1*0102 is
      secondary to that with DRB1*1501/DQB1*0602. Analysis of the diagnostic value of
      typing for the narcolepsy-associated alleles demonstrated a very high negative
      predictive value and revealed that this test can be convenient for exclusion of
      narcolepsy in cases when the diagnosis is not evident after clinical evaluation
      and the marker haplotype is absent. Finally, a family study indicated that
      narcolepsy is a multifactorial disorder that involves HLA genes under an
      incomplete penetrance model, with possible influences from environmental factors
      or other genes different to HLA genes.

PMID- 9534040
TI  - Hierarchy of SPEA presentation to T cells by mouse MHC haplotypes.
AB  - The ability of splenic antigen-presenting cells (APC) from nine independent mouse
      major histocompatibility complex (MHC) haplotypes to present recombinant
      streptococcal exotoxin A (rSPEA) to heterogeneous T cells and mouse T cell clones
      were compared using proliferation assays. We report that there is marked
      variation between MHC haplotypes, which can be ranked as follows: H2z > H2s = H2f
      = H2p = H2r = H2k > H2d > H2b = H2q. In some haplotypes both A and E molecules
      bind rSPEA with low affinity. In addition, we show that presentation is
      preferentially by E molecules in haplotypes where A and E are coexpressed, but
      that A alleles also bind and present rSPEA, based on inhibition of responses by
      anti-E and anti-A mAbs. Furthermore, using strains of mice which fail to express
      E, we demonstrate that A(s) and Af present rSPEA with high efficiency, whereas Aq
      and Ab are the least efficient of all haplotypes. The results suggest that there
      is significant variation in the ability of different alleles of both E and A
      molecules to bind and present rSPEA.

PMID- 9534041
TI  - Sequence of HLA-DRB1*0818 in a bone marrow donor.
AB  - Exon 2 of a new HLA-DR8 subtype, DRB1*0818, was cloned and sequenced in a
      volunteer bone marrow donor. This new allele differs from DRB1*0805 by one single
      nucleotide in codon 67 resulting in an amino acid substitution from phenylalanine
      to isoleucine. Codon 67 dimorphism appears to be more frequent in DR8 and DR11
      haplotypes. The HLA typing of the donor was A*0201/33 B*51/4403 Cw*0202/14
      DRB1*0408/0818 DQB1*0302/0402. This new HLA-DR8 variant is very rare, at least in
      Caucasoids.

PMID- 9534042
TI  - A novel DRB1*0801 haplotype carrying DRB3*0202 found in a German pedigree.
AB  - DRB1*08 haplotypes have not been known to carry a DRB3 gene. We have found a
      patient suffering from liver disease who has a novel HLA haplotype of DRB1*0801
      with DRB3*0202 as established by family segregation. These two genes were
      confirmed by sequencing. DR8 and DR52 antigen specificities were serologically
      detected, indicating expression of these genes.

PMID- 9534043
TI  - HLA and elephantiasis revisited.
AB  - A recent case-control study in Indonesia suggested that the course of Brugian
      filariasis and in particular resistance to the development of elephantiasis was
      associated with certain HLA class II alleles. In order to see whether these data
      could be confirmed we conducted a similar study in another Indonesian population
      from South Sulawesi. We could not confirm our earlier results and therefore
      concluded that HLA-DR and -DQ alleles are at least not strongly associated with
      progression to elephantiasis in Brugian filariasis. The complete data are
      presented also for anthropological reference purposes.

PMID- 9534044
TI  - Compilation of distinct HLA-A, -B and -C transmembrane and cytoplasmic domain
      encoding sequences.
AB  - Exons 5-8 of HLA class I genes encode the transmembrane and cytoplasmic domains
      of HLA class I proteins. Of the more than 300 HLA-A, -B and -C alleles recognized
      by the WHO Nomenclature Committee for Factors of the HLA System, the number of
      alleles for which exon 5-8 sequence information is available and the extent of
      genetic variability in this region are undocumented. Thus, a comprehensive
      analysis of HLA-A, -B and -C exon 5-8 sequence variability was undertaken. Of 219
      HLA-A, -B and -C alleles for which exon 5-8 sequences are known, 40 unique HLA-A,
      -B and -C exon 5-8 sequences were identified. At the amino acid level, these
      encode 28 distinct HLA-A, -B and -C transmembrane and cytoplasmic domains.

PMID- 9534045
TI  - Nomenclature for factors of the HLA system, update July/August 1997.

PMID- 9534046
TI  - Nomenclature for factors of the HLA system, update September/October 1997.

PMID- 9534047
TI  - Function and specificity of human natural killer cell receptors.
AB  - In humans, natural killer lymphocytes express HLA class I-specific inhibitory
      receptors belonging to at least two different molecular families. The first is
      represented by members of the Ig superfamily that are involved in the recognition
      of different groups of HLA class I alleles, and the second is represented by a
      molecular complex formed by CD94 and NKG2A that displays a broad specificity for
      various class I molecules including the 'non-classical' HLA-G molecules. In
      addition to the inhibitory receptors, a series of activating receptors has been
      identified. Some display the same specificities as the corresponding inhibiting
      receptors and can be viewed as HLA class I-specific activating receptors. Another
      group of activating receptors appear to be involved in the cytolytic activity
      against HLA-'negative' target cells. These receptors are clearly non-MHC specific
      and, under physiological conditions, their function is suppressed by the HLA
      class I-specific inhibitory receptors.

PMID- 9534048
TI  - The effects of endocardial defibrillation on left ventricular function: a
      transoesophageal echocardiographic study.
AB  - This study evaluates the immediate effects of the endocardial electrical shocks
      delivered by a transvenous defibrillation system on left ventricular (LV)
      function in a pig model. A triple-lead system consisting of two endocardial
      electrodes, in the right ventricular apex and the junction of superior cava-right
      atrium, and a custom-made defibrillation can implanted subcutaneously in the
      thorax was set up in 10 close-chest pigs. Transesophageal echocardiography with
      two dimensional image, m-Mode, and pulse Doppler was performed at baseline and
      after several episodes of fibrillation/defibrillation (F/DF). Each animal
      underwent an average of 8 (range 6 to 11) episodes of ventricle F/DF for a total
      of 210 (range 165 to 290) joules of biphasic-waveform defibrillation shocks.
      Heart rate, blood pressure, LV end-systolic area, end-diastolic area and
      fractional area contraction, isovolumic relaxation time, and both ratios of
      velocities and time-velocity integrals in transmitral Doppler flow E and A waves
      were unchanged after the shocks. This animal study suggests that multiple
      countershocks up to 210 joules delivered by a transvenous defibrillation system
      do not cause LV global systolic and/or diastolic dysfunction.

PMID- 9534049
TI  - RITED (Registro Italiano Test Eco-Dobutamina): side effects and complications of
      echo-dobutamine stress test in 3041 examinations.
AB  - AIM: The aim of the study was to report the incidence and clinical meaning of
      side-effects caused by echo-dobutamine testing in a large population and to
      evaluate any possible correlation between dobutamine dose and side-effects.
      METHODS: The study population consisted of 3041 patients enrolled from January
      1994 to August 1995 at 63 centers participating in the Italian Register of Echo
      Dobutamine Testing (Registro Italiano Test Eco-Dobutamina, RITED). The four major
      indications were myocardial infarction older than one month (40.4%), recent
      myocardial infarction (22.7%), coronary artery disease without a history of
      myocardial infarction (10.8%) and suspected coronary artery disease (19.3%).
      Dobutamine was administered in a peripheral vein at 5, 10, 20, 30, 40
      micrograms/kg/minute + atropine 1 mg in four divided doses of 0.25 mg/minute.
      RESULTS: Severe complications were asystole, which went as high as 6" in one
      patient, and ventricular fibrillation in two patients. The clinical side-effects
      were headache (2.5%), hypotension (2.2%), nausea (1.7%), bradycardia (1.4%),
      palpitations (0.5%), tremors (0.3%), dyspnea (0.2%), paresthesia (0.2%) and
      hypertension (0.2%). Atrial arrhythmia was recorded in 10.6% of patients, while
      ventricular arrhythmia was recorded in 26.5%. The percentage of supraventricular
      and ventricular repetitive arrhythmia did not increase with dosage. The
      cumulative incidence of supraventricular and ventricular repetitive arrhythmia,
      considered as an interruption criteria, was 6.6% and 5.9%, respectively.
      CONCLUSIONS: Echo-dobutamine stress test seems to be a very safe and reliable
      test for unmasking myocardial ischemia or viability in known or suspected
      coronary artery disease. It has been shown to be widely applicable in clinical
      practice for outpatients as well, as long as a protected environment is
      available.

PMID- 9534051
TI  - [Editorial comment on the article: "Early aggressive treatment of unstable angina
      without on-site cardiac surgical facilities: a prospective study of acute and
      long-term outcome"].

PMID- 9534050
TI  - Early aggressive treatment of unstable angina without on-site cardiac surgical
      facilities: a prospective study of acute and long-term outcome.
AB  - BACKGROUND: The early invasive diagnostic approach with extensive use of
      myocardial revascularization in patients with unstable angina is a matter of
      debate. Both the advantages of this strategy and the choice of the best
      candidates are controversial. The widespread applicability of this approach in
      Italian hospitals is also questionable, due to limited availability of facilities
      for interventional cardiology. METHODS: A prospective, observational study was
      done on a cohort of consecutive patients, who were admitted with a diagnosis of
      unstable angina and treated with an early aggressive approach at a center with
      interventional cardiology facilities without cardiac surgery. The aim of the
      study was to evaluate both the immediate and long-term clinical outcome of
      patients and the efficiency of our therapeutic approach. RESULTS: Two-hundred and
      two patients were enrolled and 85% were in Braunwald class III. Coronary
      angiography was performed in 171 patients (85%) at 2.1 +/- 2.4 days after
      admission: it showed one-, two- and three-vessel disease in 40, 29 and 22% of
      cases, respectively; 9% of patients had no severe coronary lesion. Left
      ventricular ejection fraction was 0.58 +/- 0.13. Medical treatment, coronary by
      pass surgery and percutaneous myocardial revascularization were chosen in 36, 24
      and 40% of cases, respectively. Coronary angioplasty was performed in our center
      in 58 (73%) of 80 patients at 6.8 +/- 5.6 days after admission and stents were
      used in 42 cases (74%). Overall hospital stay was 10.4 +/- 4 days. Cumulated
      adverse events (death and non-fatal myocardial infarction) occurred in 2.5 and 7%
      of patients during the initial admission and in the following year, respectively.
      CONCLUSIONS: An early aggressive approach to patients with unstable angina is
      feasible in a hospital with interventional cardiology in the absence of cardiac
      surgical facilities. The immediate favorable clinical results of this strategy in
      an intermediate-risk cohort seem to persist at one-year follow-up.

PMID- 9534052
TI  - Diagnostic approach to acute pulmonary embolism in a general hospital. A two-year
      analysis.
AB  - BACKGROUND: Several approaches have been proposed for the diagnosis of acute
      pulmonary embolism (PE), but little is known about the strategies effectively
      used in daily clinical practice. METHODS: Retrospective evaluation of the
      diagnostic strategy used in our institution in the patients (pts) discharged
      between January 1st 1995 and December 31st 1996 with diagnostic code 415.1,
      corresponding to acute PE in the International Classification of Disease.
      RESULTS: One-hundred-twenty-seven patients (49 M; 78 F; mean age: 71.5 +/- 15
      years; range: 25-95) were identified. Electrocardiogram, chest X-ray, blood gas
      analysis and plasma D-dimer measurement were performed in 122 (96%), 121 (95%),
      114 (90%) and 86 (68%) pts, respectively. Out of the 102 pts surviving the
      initial phase (early mortality: 20%), 83 (81%) underwent lung scintigraphy, 10
      (10%) spiral CT scanning and 2 (2%) pulmonary angiography, while 7 (7%) were
      treated directly. Thirty of the 83 pts undergoing lung scintigraphy had non
      diagnostic results, but only 8 of them underwent further investigation (with
      spiral CT in 6 cases and pulmonary angiography in 2 cases). Transthoracic
      echocardiography and ultrasonography of the lower limbs were used in 49 (48%) and
      74 (73%) pts respectively, for diagnostic confirmation and to search for the
      embolic source. CONCLUSIONS: At our institution, where multiple and modern
      diagnostic facilities are available, ventilation/perfusion lung scanning still
      represents the most frequently used imaging technique. Spiral CT is employed
      quite often as an alternative to either lung scintigraphy or pulmonary
      angiography which, in turn, is used very seldom. Ultrasonography of the lower
      limbs is widely utilized (although not in a serial manner and only as a second
      line test), while the role of echocardiography appears to be marginal. Spiral CT,
      pulmonary angiography and lower-limb ultrasonography showed high diagnostic
      accuracy, while the accuracy of lung scintigraphy and echocardiography was
      confirmed as being suboptimal. However, due to the retrospective design of our
      study and the characteristics of our population, these results cannot be
      extrapolated to pts referred for suspected acute PE, in whom further
      investigations are thus warranted in order to identify the most cost-effective
      diagnostic approach.

PMID- 9534054
TI  - [A competitive model for supply of materials for hemodynamics].
AB  - INTRODUCTION: Cardiology and above all haemodynamics are among the specialities
      that have received the most emphasis in recent years and remarkable results have
      been achieved, thanks to technological developments in materials. In practice,
      therefore, the need to be able to access these required and qualitatively better
      materials, comes up against the need of state-run companies to prepare and
      finalize the tenders necessary for the purchase of any goods. METHODS: There are
      essentially three problems to be faced in relation to the need to keep costs
      down: the large number and the different kinds of medical apparatus to be used,
      the possibility of reusing expensive materials which enables the use of different
      configurations without inordinately increasing prices, and the need to hold long
      and complex tenders. RESULTS/CONCLUSIONS: We have decided to supply a pro-forma
      product description for use in public tenders in order to facilitate the methods
      for detailing technical characteristics and quality measurement so that medical
      users can attain a good price quality ratio.

PMID- 9534053
TI  - [The heart of anorexic adolescents].
AB  - BACKGROUND: Anorexia nervosa (AN) is often associated with cardiac changes, such
      as thinning of the left ventricle (LV), reduction of LV mass, abnormalities of
      mitral valve function and systolic dysfunction. Some authors have reported QT
      interval prolongation and sudden death in these patients. METHODS: We studied 23
      adolescent females, aged 14.7 +/- 2 years (mean +/- SD), with AN. Serum
      electrolytes, proteins and albumin were measured in all patients.
      Electrocardiogram, Doppler-echocardiogram and chest X-rays were also performed on
      the same day. Eighteen patients were also examined via indirect calorimetry
      (difference from basal metabolic rate) and 21 underwent dosage of thyroid
      hormones. RESULTS: The patients, who were of normal height (159 +/- 7.4 cm), were
      underweight (36 +/- 4.8 kg) and had a body mass index (BMI) of less than 19 (14.2
      +/- 1.3). Serum electrolytes, proteins, albumin and chest X-rays were
      substantially normal in all patients; 74% of them showed reduction of FT3. The
      calorimetry was reduced (-27.1 +/- 10.6%) with the exception of one patient.
      Resting heart rate was 58 +/- 12 bpm. We found normal values for PR, QRS, QT
      (0.41 +/- 0.03 s1/2) and QTc intervals (0.40 +/- 0.03 s1/2) and QT dispersion
      (40.9 +/- 14.1 ms). Echocardiography showed a reduction in the dimensions of the
      interventricular septum (52% of patients), LV free wall (61%), left atrium (31%)
      and LV mass (61%). Fractional shortening was normal in all but one patient. In
      61% of cases, there was mild or moderate pericardial effusion that was clinically
      silent and inversely related to BMI (r = -0.38, p 0.08, ns), to calorimetry (r = 
      0.56, p < 0.0055), to FT3 (r = -0.53, p < 0.05) and to sodium concentration (r = 
      0.43, p 0.04). CONCLUSIONS: Teen-agers with AN often show a reduction in LV
      thickness and mass, as well as clinically silent pericardial effusion that is
      inversely related to BMI, calorimetry, FT3 and sodium serum concentrations. We
      did not find any prolongation of QTc interval or of QT dispersion.

PMID- 9534055
TI  - [Doppler tissue imaging in the study of the diastolic function in amyloidosis
      cardiopathy].
AB  - Doppler tissue imaging (DTI) is an adaptation of the color-doppler, which allows
      the measurement of low-speed myocardial wall movement. We describe the case of a
      51-year-old woman suffering from cardiac amyloidosis with serious endangerment of
      the diastolic function and mitral flow velocity pattern that was
      indistinguishable from the normal. The protodiastolic speed of the myocardial
      walls was measured with pulsed DTI, which was used as a diastolic function index.
      In this patient, the speed was 5 cm/sec, which was markedly lower than the values
      found in normal subjects and published recently. Moreover, the DTI M-mode images
      are examined here in order to point out different characteristics compared to the
      ones that can be obtained in normal subjects. This therefore exemplifies the
      possible use of this new technique in studying diastolic function.

PMID- 9534056
TI  - Aortic valve fibroelastoma: transesophageal echocardiographic diagnosis and
      surgical excision.
AB  - An asymptomatic 31-year-old woman was admitted for evaluation of a heart murmur
      accidentally discovered at a routine medical examination. A transesophageal
      echocardiogram disclosed an ostium secundum atrial septal defect and a small mass
      attached to the inner surface of the non-coronary cups of the aortic valve. The
      patient underwent closure of the atrial septal defect and excision of the mass
      without damage to the aortic valve. Hystological analysis of the mass was
      consistent with the diagnosis of papillary fibroelastoma. Papillary fibroelastoma
      is the most common of the cardiac valve tumors. It is benign, generally small and
      asymptomatic, but it has a definite tendency to produce serious embolic
      complications. Therefore, elective surgical resection is usually recommended. The
      tumor is most often an incidental finding at autopsy; occasionally it is
      recognized during life in patients evaluated for embolic events of unclear
      ethiology. This is one of a few cases in which the diagnosis of a completely
      asymptomatic fibroelastoma has been accomplished preoperatively, thus allowing a
      successful surgical therapy.

PMID- 9534057
TI  - [The role of LDL in the origin and progression of atherosclerosis:
      pathobiological concepts on the origin and development of atherosclerotic lesions
      and the role of the endothelium].
AB  - The existence of a causal relation between elevated cholesterol levels and
      atherosclerosis is now considered an established fact, while cellular and
      molecular mechanisms underlying this relationship begin only now to be
      unravelled. The first stage of atherosclerosis development is the fatty streak, a
      focal accumulation of blood-derived lipid-laden macrophages in the arterial
      intima. The endothelium, which plays a pivotal role in vascular homeostasis,
      undergoes major functional changes under the influence of "oxidized" and
      "minimally-modified"-LDL, able to promote "endothelial activation", with the
      expression of adhesion molecules and chemoattractants for monocytes. Endothelial
      activation seems to be the transducer of atherogenic signals in the first stages
      of development of atherosclerosis. LDL also play a further crucial role in the
      progression and the instabilization of the plaque, and in the pathogenesis of
      functional changes of vasomotor tone.

PMID- 9534058
TI  - [Prevention and therapy of vascular damage and endothelial dysfunction with
      hypocholesteremic agents].
AB  - Several recent pieces of clinical evidence have demonstrated that reduction of
      cholesterol levels positively affects outcomes in both primary and secondary
      prevention of atherosclerotic vascular disease. The mechanism for the beneficial
      effects of cholesterol-lowering interventions has been attributed to decreased
      progression or actual regression of plaques as a consequence of reduced
      circulating LDL concentrations. Other mechanisms can be hypothesized, including a
      "stabilizing" effect on plaques, which would decrease chances of rupture, and an
      improvement of endothelial dysfunction, which would slow-down the progression of
      the disease. This review is aimed at offering an update on such mechanisms. The
      hypothesis of a direct action of cholesterol-lowering agents, in particular of
      statins, on endothelial functions, independently of LDL-lowering effects, will be
      discussed.

PMID- 9534060
TI  - [Developmental changes of cardiac mechanics during fetal and postnatal life.
      Diagnostic role of Doppler echocardiography].
AB  - The advent of fetal echocardiography combined with Doppler technology gave the
      clinicians the possibility to evaluate and clarify the main aspects of fetal and
      postnatal circulatory physiology. From the end of cardiogenesis to the end of
      gestation the developmental changes of the fetal myocardial structure,
      ventricular function and circulatory physiology have all been studied. Also the
      physiological features of the transitional circulation in the first postnatal
      period, as well as the developmental changes in the morphology and function of
      the neonatal ventricles can be assessed by Doppler echocardiography. This review
      is divided in two parts. In the first one we will briefly discuss the contractile
      properties of the fetal myocardium, the cardiac performance and dynamics of the
      fetal circulation; in the second one we will consider the physiological aspects
      of the transitional circulation, the structural features of the immature neonatal
      myocardium, as well as the developmental changes of the myocardial mechanics as
      shown by Doppler ultrasound.

PMID- 9534059
TI  - [Anticoagulant prophylaxis: from clinical trials to clinical practice].
AB  - Anticoagulant therapy has recently undergone a surge in popularity with the
      confirmation of its importance in preventing cerebral thromboembolism from atrial
      fibrillation. Unfortunately oral anticoagulants have an extremely narrow
      therapeutic index and many physicians are reluctant to treat, particularly old
      patients, because of the fear of hemorrhagic complications and difficulty of
      management. The anticoagulant clinic, by improving therapeutic effectiveness and
      reducing complications, hospitalization and emergency room visits, appears to
      offer important qualitative and cost advantages over routine medical care. New
      strategies have been developed for managing care. One promising modality employs
      patients in their own care by performing their prothrombin time measurement by
      themselves at home. This model, similar to the way diabetics measure their own
      blood sugar, is possible as a result of a new class of point-of-care
      instrumentation for prothrombin testing. These portable monitors can measure a
      prothrombin time from a finger-stick sample of whole blood and provide a result
      within seconds. However rigorous studies are necessary to confirm the preliminary
      results of new management strategies to maximize the benefit-risk ratio of
      anticoagulant therapy.

PMID- 9534061
TI  - Three-dimensional transesophageal echocardiographic evaluation of a left atrial
      myxoma.

PMID- 9534062
TI  - [After myocardial infarct: update on the rationale of coronarography prior to
      patient discharge].

PMID- 9534063
TI  - [70th scientific session of the American Heart Association. November 9-12, 1997,
      Orlando, USA].

PMID- 9534064
TI  - [Quality and organizational aspects of primary PTCA: a comment].

PMID- 9534065
TI  - Surgical diode lasers.

PMID- 9534067
TI  - Electrosurgical units.

PMID- 9534068
TI  - Separation of bard endoscopic overtubes.

PMID- 9534070
TI  - Premature depletion of datascope 97 intra-aortic balloon pump helium cylinders.

PMID- 9534069
TI  - Inspection and preventive maintenance--don't forget the nuts and bolts.

PMID- 9534071
TI  - Unnecessary initiation of the warm-up routine on GE prospeed CT scanners.

PMID- 9534072
TI  - The effect of implicit and explicit motivation on recall among old and young
      adults.
AB  - Seventy-six elderly subjects aged sixty-five to eighty-seven and seventy-seven
      young adults aged twenty-five to forty were compared on implicit and explicit
      motive levels and on recall of introductions and working memory. Significantly
      fewer of the elderly than the young participants scored high in the implicit
      motives, n Affiliation and n Power, confirming results from U.S. national
      surveys. The surveys also demonstrated a significant decline with age in high
      levels of n Achievement, a decline not found here. The elderly participants
      showed major recall deficits on both tasks, but all three of the implicit motives
      studied were shown to enhance recall for the elderly, but not for the young
      adults. Eight elderly women scoring high on at least two of the three motives
      showed no recall deficits compared to the young women on two memory tasks. In old
      age implicit motive deficits contribute to poor memory but explicit commitments
      to have a good memory had no effect on recall.

PMID- 9534073
TI  - On a recognition task in which some distractors were half-familiar.
AB  - Models are suggested for the task of recognizing word-pairs, where the
      distractors may be pairs of new words, or may be a new word paired with a
      previously-seen word. These models are relevant to an experiment recently
      reported by Isingrini et al., and suggest rather different conclusions to theirs-
      namely, that the elderly differ from the young in both learning and response
      selection.

PMID- 9534074
TI  - A life review interview guide: a structured systems approach to information
      gathering.
AB  - This clinical project introduces a guide to provide the interviewer with a
      methodological systems approach for information gathering in the life review
      process. The guide is structured in such a way as to elicit positive life events
      for the purpose of enhancing a sense of well-being as well as to elicit negative
      life events to encourage the client to address unresolved loss-grief issues. In
      effect, the Life Review Interview Guide serves to promote high self-esteem and to
      assist the interviewee through the grieving process. In addition, the Guide
      assisted the student-interviewer in formulating and selecting a wide range of
      questions.

PMID- 9534075
TI  - The self-portrait in adulthood and aging.
AB  - Ninety-eight participants aged thirty to eighty-five, drew a self-portrait in
      which the depiction of face features and limb extremities was studied.
      Statistical multivariate analysis permitted to describe three classes of drawings
      with different modes of representation of hands and face features. The
      representation of the hands was problematic in most of the participants
      regardless of age. There was a relation between age and not representing the face
      features: 17 percent of the participants over sixty-five did not represent the
      face features vs. none of the younger participants. Results are discussed from a
      psychoanalytic perspective. The difficulties in representing the hands are
      discussed in relation to castration. The absence of face features in the
      portraits of some elderly drawers could indicate a minimal age-related defect of
      the network which establishes that the real mouth and eyes are both symbolic body
      orifices and imaginary face features. The comments made by some drawers strongly
      suggest that this absence may also represent an incapacity to face the losses
      imposed by aging.

PMID- 9534076
TI  - Housing quality among the elderly: a decade of changes.
AB  - Little research has been conducted on housing quality among the elderly. The
      fault lies partly with the lack of reliable data. Studies on elderly housing
      quality are spotty, anecdotal, and unsystematic. Many rely on decennial census
      data which provide a limited and unsatisfactory portrait of special housing needs
      of elders in general. This article seeks to fill this void by reporting a
      comprehensive study of elderly housing quality. For all units, logistic
      regression revealed that region and race are the most important predictors of
      housing inadequacy; tenure and the gender of the person living alone are
      moderately powerful influences upon inadequacy. Housing inadequacy is greater
      among blacks, in the South, for males living alone, and for renters.

PMID- 9534077
TI  - Consistency in preventing voluntary dehydration in boys who drink a flavored
      carbohydrate-NaCl beverage during exercise in the heat.
AB  - Twelve 10- to 12-year-old healthy boys performed six 70-min intermittent exercise
      sessions (three 20-min cycling bouts at 50% VO2max with 5 min rest in between)
      over a 2-week period at 35 +/- 1 degrees C, 50 +/- 5% or 60 +/- 5% relative
      humidity. Subjects drank grape-flavored solution with 6% carbohydrate (2%
      glucose, 4% sucrose) and 18.0 mmol.L-1 NaCl ad libitum. Body weight (BW), heart
      rate, rectal temperature, thirst, and stomach fullness perception were monitored
      periodically. There were no differences among the six sessions in voluntary drink
      intake (765-902 g), hydration level (+0.75 to +1.07%BW), sweating rate (245-263
      g.m-2.hr-1), and the other physiological and perceptual variables. A positive
      fluid balance was achieved in 67 out of 72 sessions. Voluntary drink intake of
      grape-flavored carbohydrate-NaCl beverage was consistently sufficient to prevent
      dehydration in 10- to 12-year-old boys during repeated exposures of exercise in
      the heat. This effect is likely to be achieved through a combination of
      physiological and behavioral mechanisms.

PMID- 9534078
TI  - Examination of the self-selected fluid intake practices by junior athletes during
      a simulated duathlon event.
AB  - Thirty-two elite junior athletes in two age categories, older than or equal to 15
      years old (O15) (8 females and 9 males) and less than 15 years old (U15) (8
      females and 7 males), performed a laboratory-based duathlon (run-ride-run). At
      the completion of the event, significant body mass losses were recorded for all
      groups. Compared with the other three groups, the O15 males lost body mass at a
      greater absolute rate (1.26 +/- 0.06 kg.hr-1 vs. a mean of 0.62 +/- 0.11 kg.hr-1
      for the other three groups) and a greater relative rate (1.95 +/- 0.10%BM.hr-1
      vs. a mean of 1.23 +/- 0.19%BM.hr-1 for the other three groups) (p < .05). No
      differences were observed between groups for fluid consumption. Subjects consumed
      more fluid (p < .05) during the cycle phase and postevent than preevent or during
      the run phases. Results indicated that the athletes' fluid intake practices were
      insufficient to maintain adequate hydration during the simulated event.

PMID- 9534079
TI  - Nutritional and fluid intake in a 100-km ultramarathon.
AB  - The fluid and food intakes of 7 male participants in a 100-km ultramarathon were
      recorded. The mean exercise time was 10 hr 29 min. Nutrient analysis revealed a
      mean intrarace energy intake of 4,233 kJ, with 88.6% derived from carbohydrate,
      6.7% from fat, and 4.7% from protein. Fluid intake varied widely, 3.3-11.1 L,
      with a mean of 5.7 L. The mean decrease in plasma volume at 100 km was 7.3%,
      accompanied by an estimated mean sweat rate of 0.86 L.hr-1. Blood glucose
      concentrations remained normal during the event, and free fatty acids and
      glycerol were elevated both during and at the conclusion of the event. No
      significant correlations were found between absolute amounts and rates of
      ingestion of carbohydrate and/or fluid and race performance.

PMID- 9534080
TI  - Nutritional practices of elite female surfers during training and competition.
AB  - The aim of this study was to assess the dietary practices of 10 elite female
      surfers. Four- and five-day food diaries completed over competition and training
      periods demonstrated energy intakes (mean +/- SD) of 9,468 kJ (+/- 2,007) and
      8,397 kJ (+/- 1,831), respectively. This level of energy intake was less than
      that estimated for the requirements of surfing. Female surfers' carbohydrate
      intakes failed to meet the recommendations, and suboptimal zinc intake was
      observed with 90% of subjects not meeting the Australian RDI. Comparisons between
      competition and training demonstrated that carbohydrate (g and g/kg body weight)
      and confectionary (g) intakes were significantly higher (p < .05) and protein
      intake was significantly lower (p < .05) during competition. These results show
      that although body fat stores were not compromised (mean 22%), self-reported
      energy, carbohydrate, and nutrient intakes were marginal in elite female surfers.
      Questionnaires revealed that 90% of surfers did not have good nutritional habits
      while traveling, which was compounded by a lack of knowledge of nutritional
      practices.

PMID- 9534081
TI  - Effect of low- and high-carbohydrate diets on the plasma glutamine and
      circulating leukocyte responses to exercise.
AB  - We examined the effects of a low-carbohydrate (CHO) diet on the plasma glutamine
      and circulating leukocyte responses to prolonged strenuous exercise. Twelve
      untrained male subjects cycled for 60 min at 70% of maximal oxygen uptake on two
      separate occasions, 3 days apart. All subjects performed the first exercise task
      after a normal diet; they completed the second exercise task after 3 days on
      either a high-CHO diet (75 +/- 8% CHO, n = 6) or a low-CHO diet (7 +/- 4% CHO, n
      = 6). The low-CHO diet was associated with a larger rise in plasma cortisol
      during exercise, a greater fall in the plasma glutamine concentration during
      recovery, and a larger neutrophilia during the postexercise period. Exercise on
      the high-CHO diet did not affect levels of plasma glutamine and circulating
      leukocytes. We conclude that CHO availability can influence the plasma glutamine
      and circulating leukocyte responses during recovery from intense prolonged
      exercise.

PMID- 9534082
TI  - Sodium bicarbonate ingestion does not attenuate the VO2 slow component during
      constant-load exercise.
AB  - We examined the effects of sodium bicarbonate ingestion on the VO2 slow component
      during constant-load exercise. Twelve physically active males performed two 30
      min cycling trials at an intensity above the lactate threshold. Subjects ingested
      either sodium bicarbonate (BIC) or placebo (PLC) in a randomized, counterbalanced
      order. Arterialized capillary blood samples were analyzed for pH, bicarbonate
      concentration ([HCO3-]), and lactate concentration ([La]). Expired gas samples
      were analyzed for oxygen consumption (VO2). The VO2 slow component was defined as
      the change in VO2 from Minutes 3 and 4 to Minutes 28 and 29. Values for pH and
      [HCO3-] were significantly higher for BIC compared to PLC. There was no
      significant difference in [La] between conditions. For both conditions there was
      a significant time effect for VO2 during exercise; however, no significant
      difference was observed between BIC and PLC. While extracellular acid-base
      measures were altered during the BIC trial, sodium bicarbonate ingestion did not
      attenuate the VO2 slow component during constant-load exercise.

PMID- 9534083
TI  - Blood glucose and glucoregulatory hormone responses to solid and liquid
      carbohydrate ingestion during exercise.
AB  - This study was conducted to compare blood glucose and glucoregulatory hormone
      responses to the ingestion of solid and liquid carbohydrate (CHO) during
      prolonged cycling, followed by 30 min of isokinetic cycling. Eight male cyclists
      randomly completed three cycling trials (LC = liquid CHO, SCE = solid CHO with
      water equal to LC, SCA = solid CHO + ad libitum water). Each subject cycled for
      120 min at 65% of VO2max with CHO ingestion (0.6 g CHO/ kg/hr) at 0, 30, 60, 90,
      and 120 min. Subjects then completed a 30-min maximal isokinetic ride at 90 rpm.
      There was no significant (p < .05) difference between the trials for plasma
      glucose, insulin, glucagon, glycerol, lactate, RER, HR, VO2, RPE, and total work
      performed during the isokinetic ride. However, serum glucose was significantly
      lower in the SCE and SCA trials compared to LC at 80 min. The ingestion of a
      solid food containing CHO, protein, and fat with added water produced similar
      blood glucose, metabolic, glucoregulatory hormone, and exercise performance
      responses to those seen with the ingestion of liquid CHO.

PMID- 9534084
TI  - The development of memory.
AB  - This article reviews recent advances in understanding the changes in memory
      function that take place during the childhood years. Development of the following
      aspects of memory are considered: short-term memory, comprising phonological
      memory, visuospatial memory, and executive function; autobiographical memory;
      episodic memory, including eyewitness memory; and metamemory. Each of these
      aspects of memory function shows substantial qualitative change from infancy,
      through the preschool period, to the early school years. Beyond about 7 years of
      age, however, memory function appears adult-like in organisation and strategies,
      and shows only a gradual quantitative improvement through to early adolescence.

PMID- 9534085
TI  - Effects of pediatric chronic physical disorders on child and family adjustment.
AB  - Research conducted primarily over the past 5-8 years on the psychosocial effects
      of pediatric chronic physical disorders on children and their families is
      reviewed. A large body of studies show that both children and their mothers, as
      groups, are at increased risk for psychosocial adjustment problems compared to
      peers, but that there is considerable individual variation in outcome. Since the
      last review on this topic (Eiser, 1990a), many studies have been conducted to
      identify risk and resistance factors associated with differences in adjustment
      among these children and their mothers. Improvements are noted in the theoretical
      basis for this work, programmatic nature of some of the research, and efforts at
      producing clinically relevant information. Evaluations of interventions, however,
      are lagging. Critical issues and future directions regarding developmental
      approaches, theory, method, measurement, and intervention are discussed.

PMID- 9534086
TI  - Internalizing disorders in childhood.
AB  - In this selective review of recent research on internalizing disorders in
      childhood, we focus on four areas: the predictive validity of the diagnoses of
      depressive and anxiety disorders, rates of comorbidity, the chronology of onsets
      of the disorders of interest, and transmission of depressive and anxiety
      disorders in the pedigrees of affected individuals. To synthesize and reconcile
      findings in these four areas, we approach the information from a developmental
      perspective and assume that genetically driven biologic processes play a salient
      role in the expression of depressive and anxiety disorders in childhood. We also
      comment on the relevance of findings on children and adolescents to the field of
      depressive and anxiety disorders in adults and make recommendations for further
      research.

PMID- 9534088
TI  - Research update: childhood-onset schizophrenia: implications of clinical and
      neurobiological research.
AB  - Childhood-onset schizophrenia is a rare, clinically severe form of schizophrenia,
      which is associated with disrupted cognitive, linguistic, and social development
      well before the appearance of frank psychotic symptoms. This disruption of
      multiple developmental domains signals the important opportunity these patients
      present for examining neurodevelopmental and other etiologic hypotheses of
      schizophrenia. The present research update reviews studies of the phenomenology
      and neurobiology of childhood-onset schizophrenia conducted since 1994. Findings
      from these studies indicate that children can be diagnosed with schizophrenia
      using unmodified DSM-III, -IIIR, and -IV criteria, and that the atypical
      neuroleptic clozapine is an effective medication for this treatment refractory
      group. Neuropsychologic and neurobiologic studies generally support continuity
      with adult-onset schizophrenia, with evidence of more severe premorbid
      impairment. Longitudinal studies show preliminary evidence of progressive
      ventricular enlargement and more prolonged deterioration in intellectual function
      than is seen in the adult-onset disorder. If replicated, these observations,
      together with the insidious onset of this disorder, would suggest that the
      pathologic underpinning of childhood-onset schizophrenia is not a single static
      lesion or event but may be a continuous or multi-event process.

PMID- 9534087
TI  - Attention deficit hyperactivity disorder: advances in cognitive, neurobiological,
      and genetic research.
AB  - Conceptual and technological advances in cognitive neuroscience and molecular
      genetics have the potential to identify the pathogenesis of psychiatric
      disorders. This article reviews the application of these technologies to the
      scientific study of attention deficit hyperactivity disorder. It begins with a
      summary of shifts in conceptualization and scientific study of this common
      condition. This is followed by a critical review of findings from recent
      cognitive, neuroimaging, and genetic studies. The available data do not yet
      permit an integration across these different levels of enquiry, but implicate
      problems in response inhibition, dysfunction of frontostriatal networks, and
      genetic factors in the pathogenesis of this complex behavioral phenotype. The
      review closes with suggestions for future interdisciplinary research.

PMID- 9534089
TI  - Categorical models of childhood disorder: a conceptual and empirical analysis.
AB  - In this review we explore the clinical and scientific status of categorical
      models of childhood disorder. Three themes are developed. First, the practical
      origins of standardised category-based diagnostic schemes are examined along with
      their contemporary philosophical and psychological significance. Next, the impact
      that these systems have had on the science of child psychopathology is explored.
      We look at their link to the medical model and the assumption that childhood
      disorders are categorical, endogenous, and dysfunctional in nature. We argue that
      these assumptions underpin the dominant paradigm in child psychopathology and so
      constrain empirical study and theory development. In the final section, the
      different ways in which researchers have responded to this link and its impact on
      science are presented. We present the sort of scientific realism associated with
      Meehl (1995) as the most appropriate basis for a philosophically respectable
      child psychopathology. Following this approach means unpacking the paradigmatic
      assumptions, including the assumption of the categorical structure of disorder,
      into hypotheses that are then put to empirical test. The sorts of data that would
      allow us to test the categorical hypothesis are identified. We conclude by
      discussing the results from three recent studies using behaviour genetic analysis
      of twin data that, in fact, lead us toward a rejection of this hypothesis. The
      implications for diagnostic and clinical practice of such a rejection are
      discussed.

PMID- 9534090
TI  - Antihypertensive treatment: past, present and future.
AB  - THE PAST: Guidelines for pharmacological and non-pharmacological approaches to
      the treatment of hypertension were first published in 1977 and were subsequently
      revised in the 1980s. They were largely based on the approach known as 'stepped
      care', which suggests that antihypertensive treatment should be started with the
      initial use of a thiazide diuretic, followed by the addition of a second, third
      and fourth drug if no satisfactory therapeutic success is obtained. This approach
      was reviewed in the guidelines that followed, which indicated that
      pharmacological treatment should be started in a more liberal fashion by
      selecting the antihypertensive drug from among four rather than two classes
      (diuretics, beta-blockers, angiotensin converting enzyme inhibitors and calcium
      antagonists). THE PRESENT: The latest guidelines issued in 1993 by the World
      Health Organization/International Society of Hypertension and by the Joint
      National Committee contain innovative aspects on how to treat high blood
      pressure. They share common features, such as lifelong treatment of hypertension,
      attention to overall cardiovascular risk profile, initiation of treatment with
      lifestyle changes and subsequently with monotherapy, but they also have
      differences, such as goal blood pressure, initial blood pressure values to be
      treated and first-choice drug. For example, according to the World Health
      Organization/International Society of Hypertension guidelines first-choice drugs
      include five classes of drug, whereas the Joint National Committee guidelines
      advocate two classes of drug for first choice. THE FUTURE: It is likely that the
      'stepped care' approach for hypertension treatment will continue to be employed
      in the future, although greater attention will be devoted to the need for
      combination drug treatment. Greater importance will be also given to the non
      pharmacological antihypertensive approaches, as well as to baseline blood
      pressure values at which drug treatment should be started.

PMID- 9534091
TI  - Tachycardia: an important determinant of coronary risk in hypertension.
AB  - Heart rate and blood pressure are highly correlated and in large population
      studies, individuals with high blood pressure tend to have high heart rates. Fast
      heart rate precedes the development of high blood pressure and serves as an early
      indicator of coronary heart disease. Not only does the heart rate predict
      coronary mortality, but also the non-cardiovascular mortality and is, therefore,
      an overall predictor of longevity. In the Tecumseh Blood Pressure study, we have
      seen that 37% of all patients with borderline hypertension have the 'hyperkinetic
      hypertension state', which consists of elevated cardiac output, high heart rate,
      high sympathetic tone, and decreased parasympathetic tone. In this population,
      evidence of high heart rate exists in these individuals as children, and persists
      through early adulthood. This suggests that tachycardia is a reliable marker of
      high sympathetic tone. High sympathetic tone might be the mechanism whereby heart
      rate is associated with high insulin, insulin resistance, dyslipidemia, high
      hematocrit and excess weight. These mechanisms are discussed in details in this
      review. Tachycardia is a strong risk factor for sudden death and arrythmia. Heart
      rate, as one of the prime determinants of cardiac work, may contribute to greater
      cardiac strain. Animal studies have shown that a higher heart rate may be
      associated with a greater development of atherosclerotic plaque in coronary
      vasculature. Therefore, heart rate elevation is not merely a sign of underlying
      pathology, but it may also cause further damage that leads to increased
      mortality. In the treatment of hypertension, reducing heart rate by pharmacologic
      and non-pharmacologic measures may have a greater effect on coronary mortality
      than blood pressure reduction alone.

PMID- 9534092
TI  - Calcium antagonists and sympathetic nerve activation: are there differences
      between classes?
AB  - ACTIONS OF THE SYMPATHETIC NERVOUS SYSTEM: The sympathetic nervous system is an
      important cardiovascular regulator, particularly during stress and exercise; its
      sympathetic nervous activity is regulated in centers in the brain stem and
      transmitted to organs and blood vessels that are innervated by sympathetic nerve
      endings. In the heart, the sympathetic nervous system increases heart rate and
      contractility. The effect of the sympathetic nervous system in different vascular
      beds depends on the degree of innervation, the distribution of postjunctional
      receptors and the effect of local mediators. Overactivation of the sympathetic
      nervous system may lead to hypertension and is involved in heart failure. The
      degree of sympathetic activation determines prognosis in heart failure. Hence,
      vasodilators ideally should also blunt sympathetic activity, or at least avoid
      activating it. DIFFERENCES AMONG CALCIUM ANTAGONISTS: Calcium antagonists are
      widely used for the treatment of hypertension and coronary artery disease. Their
      main mechanism of action is inhibition of L-type Ca2+ channels. Short-acting
      nifedipine leads to a marked increase in heart rate, sympathetic nerve activity
      and plasma catecholamines, similar to those induced by a cold pressor test. With
      long-acting nifedipine heart rate does not increase, but sympathetic nerve
      activity does increase. Other calcium antagonists have been less thoroughly
      investigated, but indirect evidence suggests differences between the different
      classes. Verapamil and diltiazem lower heart rate. Plasma noradrenalin
      measurements suggest that verapamil does not stimulate the sympathetic nervous
      system, but tends to suppress it. Second-generation dihydropyridines with longer
      duration of action do not increase heart rate; their effects on peripheral
      sympathetic nerve activity are not clear. Thus, in summary, the different classes
      of calcium antagonists differ with regard to their effects on sympathetic nerve
      activation. A decrease in heart rate and nerve activity might be beneficial for
      long-term prognosis, particularly in hypertension and heart failure.

PMID- 9534093
TI  - Divergent effects of verapamil and amlodipine at rest and during exercise.
AB  - OBJECTIVE: To evaluate, in healthy volunteers, the effects of acute
      administration of two calcium antagonists with different pharmacological
      profiles, verapamil and amlodipine, on haemodynamics at rest and during exercise.
      SUBJECTS AND METHODS: Six healthy volunteers (aged 20-29 years) were randomly
      assigned to receive single oral doses of amlodipine (5 mg), slow-release
      verapamil (240 mg) or a placebo during a double-blind cross-over study. Systolic
      (SAP), diastolic and mean arterial pressures (measured using a cuff
      sphygmomanometer), heart rate (HR), cardiac index (CI, bioimpedance), rate
      pressure product (SAP x HR), and noradrenaline and adrenaline plasma levels were
      measured at rest before drug administration, and at rest and during graded
      bicycle exercise (steps of 50, 100 and 150 W during 3, 3 and 4 min, respectively)
      started 3 h after drug administration. RESULTS: At rest arterial pressure, HR,
      rate-pressure product and catecholamine plasma levels did not change after
      verapamil or amlodipine administration, whereas CI significantly decreased after
      verapamil (from 3.9 +/- 0.4 to 3.3 +/- 0.4 l/min per m2) but not after amlodipine
      (3.9 +/- 0.3 and 4.1 +/- 0.5 l/m per m2) administration. During exercise the
      increases in SAP and HR were slightly but not significantly higher after
      amlodipine than after verapamil administration, rate-pressure product and CI were
      higher after amlodipine (22 +/- 1 x 10(3) mmHg x beats/min and 13 +/- 2 l/min per
      m2, respectively) than after verapamil (20 +/- 1 x 10(3) mmHg x beats/min and 10
      +/- 2 l/min per m2, respectively) administration. Plasma levels of noradrenaline
      and adrenaline were similar at rest after each treatment and were slightly more
      increased after amlodipine administration during exercise. CONCLUSIONS: In
      contrast to amlodipine, verapamil induced a slight myocardial depressive effect
      at rest and did not potentiate the myocardial effects of the sympathetic
      stimulation induced by exercise. The myocardial action of verapamil is such as to
      induce some decrease in myocardial oxygen demand, both at rest and during
      exercise.

PMID- 9534095
TI  - Obesity in hypertension: effects on prognosis and treatment.
AB  - OBESITY AND RISK OF MORBIDITY: Obesity is becoming an increasingly important
      factor in the pathogenesis of hypertension, dyslipidemia and diabetes, which
      together with hyperinsulinemia comprise the deadly quartet of the insulin
      resistance syndrome. Obesity in the absence of these other factors is only a
      minor risk factor, but most obesity is accompanied by one or more of these,
      worsening the prognosis. The presence of obesity complicates the management of
      hypertension, probably in large part because of the concomitant insulin
      resistance which adds to the pathogenetic mechanisms and subtracts from the
      therapeutic efficacy of many antihypertensive regimens. Unfortunately, some of
      the agents used to reduce obesity may further aggravate the problem through their
      stimulation of sympathetic nervous activity. Nonetheless, in the treatment of
      hypertension in most obese patients who have relatively little excess risk,
      attempts to reduce body weight should be attempted first, through sensible
      dietary restrictions, increased aerobic exercise and judicious use of non
      hypertensinogenic appetite suppressants. Thereby, additional motivation to lose
      weight may be provided by the potential of escaping or at least delaying
      antihypertensive drug therapy. TREATMENT OF HIGHER-RISK OBESE INDIVIDUALS: Those
      obese hypertensive individuals at greater risk should be immediately started on
      antihypertensive drug therapy along with attempts to reduce the obesity. The
      choice of initial and subsequent therapy should take the patient's individual
      needs into account. For those with dyslipidemia or diabetes, diuretics and beta
      blockers should be avoided unless there are specific indications for their use
      (e.g. reactive sodium retention or postmyocardial infarction). In such patients,
      an alpha-blocker, an angiotensin converting enzyme inhibitor or a calcium
      antagonist may be more appropriate. If the first drug is not sufficient,
      combination therapy should be considered. A diuretic may be needed to overcome
      reactive sodium retention. Because most obese hypertensive individuals will not
      be able to lose much weight, effective antihypertensive drug therapy will usually
      be indicated.

PMID- 9534094
TI  - Some similarities and differences between verapamil and the dihydropyridines.
AB  - GROUPS OF CALCIUM CHANNEL BLOCKERS: The calcium channel blockers comprise a
      heterogeneous group of drugs. From both pharmacological and clinical points of
      view, they can be divided into three groups: the dihydropyridines, the
      phenylalkylamines and the benzothiazepines. REASONS FOR DIFFERENCES: There are
      important clinical and functional differences between the three groups. This may
      be explained by the fact that these families bind at different sites to the
      calcium channel. In this review, the major differences between the three groups
      are discussed, with an emphasis on verapamil.

PMID- 9534096
TI  - Plasma insulin and ankle on brachial systolic blood pressure ratio in overweight
      men with hypertension.
AB  - BACKGROUND: Hypertension is often associated with multiple metabolic
      abnormalities included in the insulin resistance syndrome. In hypertensive
      individuals, the ratio between ankle and brachial systolic blood pressure (ABI)
      is considered to be an independent cardiovascular risk factor. Insulin resistance
      has not been studied in relation to ABI ratio in men with essential hypertension
      and who are moderately overweight. OBJECTIVE: To identify whether a decrease in
      the ABI ratio is associated with the degree of abdominal obesity and, hence, with
      the biochemical characteristics of resistance to insulin. METHODS: In 166
      overweight men with mild-to-moderate essential hypertension, insulinaemia was
      measured using radioimmunoassay. The ABI ratio was measured by using a pressure
      cuff of appropriate diameter, a standard mercury sphygmomanometer and a Doppler
      probe. Patients with diabetes or arteriosclerosis obliterans of the lower limbs,
      or both, were excluded from the study. RESULTS: The ABI ratio was significantly
      associated with the degree of abdominal obesity, but also with plasma
      triglycerides and cholesterol, low high-density lipoprotein cholesterol, plasma
      glucose and insulin. In a multiple regression analysis, the ABI ratio was
      significantly and negatively associated with only two variables: age and plasma
      insulin. This result was independent of age and drug treatment of hypertension.
      CONCLUSION: Because alterations in the ABI ratio may be considered markers of the
      changes in the structure and function of the arteries of lower limbs, the study
      provides evidence that plasma insulin, independently of atherosclerotic occlusive
      lesions, can significantly influence the status of conduit arteries of the lower
      limbs.

PMID- 9534097
TI  - Actual blood pressure control: are we doing things right?
AB  - CORRELATION BETWEEN BLOOD PRESSURE AND RISK OF CARDIOVASCULAR EVENTS: The goal of
      antihypertensive treatment is to reduce morbidity and mortality from
      cardiovascular disease associated with high blood pressure values.
      Epidemiological studies have demonstrated a direct correlation between the risk
      of stroke or coronary events and blood pressure values, and randomized controlled
      trials with antihypertensive drugs have shown that an average fall in diastolic
      blood pressure (DBP) of 5-6 mmHg [or in systolic blood pressure (SBP) of 10 mmHg]
      reduces the relative risk of cerebrovascular events by 40% and of coronary events
      by 15%. Thus, it would seem appropriate to achieve the maximum tolerated blood
      pressure reduction, although there is still no consensus on how far blood
      pressure should be lowered. PROBLEMS OF BLOOD PRESSURE CONTROL: Because the
      reduction in the absolute risk for a given level of blood pressure is higher in
      elderly patients and in those with multiple risk factors, the 1996 World Health
      Organization report recommends lowering blood pressure to below 140/90 mmHg in
      elderly patients, and suggests that it might be desirable to achieve blood
      pressure values of 120-130/80 mmHg in young patients with mild hypertension.
      Recent surveys in primary care centers in Spain show blood pressure control rates
      (blood pressure < 140/90 mmHg) ranging from 13 to 26%. These insufficient rates
      denote the particular difficulty of controlling SBP in an elderly population of
      patients with essential hypertension mainly treated in monotherapy schedules. The
      picture is similar in other developed countries. In a sample of 14,000 patients
      from Western European countries the Cardiomonitor survey showed control rates of
      43% for DBP (< 90 mmHg) and 35% for SBP (< 140 mmHg). No more than 24% of treated
      hypertensive patients achieve the target (blood pressure < 140/90 mmHg) in the
      USA, and no more than 27% (DBP < 90 mmHg) in New Zealand. Preliminary reports
      from the Hypertension Optimal Treatment study indicate that in most patients
      combined therapy is required to achieve target blood pressure. Fixed combinations
      of synergistic antihypertensive drugs may help to improve both drug compliance
      and blood pressure control.

PMID- 9534098
TI  - Left ventricular hypertrophy: how to influence an important risk factor in
      hypertension.
AB  - LVH AND RISK: Left ventricular hypertrophy (LVH) is a powerful predictor of
      cardiovascular morbidity and mortality, independent from blood pressure and other
      cardiovascular risk factors. Available data indicate that patients who fail to
      achieve a reduction in LVH are much more likely to suffer cardiovascular events
      than those in whom LVH is reduced or even normalized using antihypertensive
      treatment. Reversal of LVH, therefore, represents a major goal in the treatment
      of hypertensive patients. REGRESSION OF LVH: Since obesity and dietary sodium
      intake may modulate the degree of LVH, non-pharmacological intervention has
      achieved a successful reduction in left ventricular mass (LVM). LVM is more
      closely related to 24-h blood pressure values than to clinical blood pressure
      values. Recent evidence from the Study on Ambulatory Monitoring of Blood Pressure
      and Lisinopril Evaluation has shown that the regression of cardiac hypertrophy is
      predicted to a greater degree by the effect of antihypertensive treatment on 24-h
      average blood pressure than by that on clinic or home blood pressure. The
      increase in blood pressure variability may also be an independent determinant of
      cardiovascular target-organ damage, particularly of cardiac hypertrophy. However,
      the effects of antihypertensive drugs on blood pressure variability can be
      difficult to determine, mainly because a correct measurement of variability
      requires a beat-to-beat measurement of ambulatory blood pressure; several
      measures have been proposed to evaluate the smoothness of blood pressure control
      during antihypertensive treatment. Other important determinants of LVH reduction
      are represented by baseline values of LVM, extent of blood pressure reduction and
      duration of treatment. Furthermore, the degree of cardiac hypertrophy reduction
      is not the same for the different classes of antihypertensive drugs because,
      beyond the control of blood pressure, they may interfere differently with several
      non-haemodynamic stimuli, including the renin-angiotensin-aldosterone and the
      adrenergic systems or other growth factors. A more pronounced reduction in LVM
      with angiotensin converting enzyme inhibitors and calcium antagonists has been
      demonstrated in several recent meta-analyses. The results of further multicenter
      on-going trials are awaited to evaluate definitely whether various
      antihypertensive strategies differ in their ability to reverse LVH and to
      adequately assess the relationship between changes in LVM and subsequent
      prognosis, with serial control of blood pressure values measured in the clinic
      and by ambulatory monitoring.

PMID- 9534099
TI  - Role of trough to peak efficacy in the evaluation of antihypertensive therapy.
AB  - BACKGROUND: The major outcome trials clearly demonstrate that there is benefit
      associated with treatment of hypertension, not only in a reduced incidence of
      stroke but also in a reduction in coronary heart disease. The latter reduction
      is, however, less than might be anticipated from epidemiological evidence. TWENTY
      FOUR-HOUR BLOOD PRESSURE CONTROL: Although there is still no definitive evidence
      that 24-h blood pressure control will lead to improved outcomes compared with
      drugs that provide intermittent control, there is a large body of evidence
      showing that cardiovascular target organ damage is correlated with 24-h blood
      pressure measurements and supportive evidence showing that a fall in these
      measurements can predict a probable reduction in cardiovascular target organ
      damage. TROUGH:PEAK RATIO AS AN INDEX OF BLOOD PRESSURE CONTROL: The Food and
      Drug Administration guidelines on trough:peak ratio offer an index not only of
      the 'safety' of an antihypertensive agent but also of its duration of action over
      the recommended dosage interval. Ideally, an agent should have a trough:peak
      ratio that consistently exceeds 60% and does so throughout the recommended
      therapeutic dose range. When this aim is achieved, particularly with agents that
      have intrinsic long duration of action, the evidence suggests that blood pressure
      control is sustained well beyond the dosage interval, providing 'cover' for the
      poorly compliant patient. CONCLUSION: Epidemiological evidence indicates that
      optimal antihypertensive therapy should be based upon achieving smooth and
      consistent blood pressure control over a full 24 h. This is most likely to be
      achieved by long-acting antihypertensives that are characterized by having a high
      trough:peak ratio.

PMID- 9534100
TI  - Influence of a history of arterial hypertension and pretreatment blood pressure
      on the effect of angiotensin converting enzyme inhibition after acute myocardial
      infarction. Trandolapril Cardiac Evaluation Study.
AB  - OBJECTIVE: To evaluate the influence of a history of arterial hypertension and
      the level of pretreatment blood pressure on the efficacy of the angiotensin
      converting enzyme (ACE) inhibitor trandolapril on mortality and morbidity in
      patients with acute myocardial infarction (AMI) and left ventricular dysfunction.
      METHODS: Data from the Trandolapril Cardiac Event study, in which 1749 patients
      with an enzyme verified AMI and echocardiographic evidence of left ventricular
      dysfunction were randomized in a double-blind manner to treatment with
      trandolapril or placebo, were retrospectively analysed. Follow up time was 24-50
      months (mean 26 months). RESULTS: Four hundred patients (23%) had a history of
      arterial hypertension. A total of 173 (43%) patients with a history of
      hypertension died during follow up versus 500 (37%) patients in the normotensive
      group. Treatment with trandolapril in the hypertensive individuals was associated
      with a reduction in the relative risk of death to 0.59 (95% confidence interval
      0.44-0.80), versus 0.85 (0.72-1.02) in the normotensive individuals. The
      significant reduction in mortality in hypertensive individuals persisted after
      multivariate analysis controlling for a broad spectrum of potential confounders.
      Also, benefit from ACE inhibition increased with increasing blood pressure at the
      time of randomization. Significant interactions between benefit from ACE
      inhibition and hypertension history, and systolic and diastolic blood pressure
      were found. CONCLUSION: ACE inhibition after AMI complicated by left ventricular
      dysfunction may be of particular importance in patients with a history of
      arterial hypertension or a relatively high pretreatment blood pressure. However,
      further investigations are necessary to establish the clinical impact of these
      results.

PMID- 9534101
TI  - Congestive heart failure and ischaemic heart disease treated with trandolapril
      and verapamil. DAVIT Study Group. Danish Verapamil Infarction Trial.
AB  - CLINICAL TRIALS WITH VERAPAMIL AND TRANDOLAPRIL: In the Danish Verapamil
      Infarction Trial II, verapamil improved survival in patients without heart
      failure but had no effect in patients with heart failure who were receiving
      diuretic treatment. In the Acute Infarction Ramipril Efficacy study ramipril
      improved survival in patients receiving diuretic treatment but had no effect in
      patients not receiving diuretics. COMBINATION WITH THERAPY WITH VERAPAMIL AND
      TRANDOLAPRIL: By combining verapamil with trandolapril we hypothesized that we
      could obtain an improvement in left ventricular function and prevent cardiac
      events. In an open study of 14 patients with angina pectoris and left ventricular
      ejection fraction below 40%, treatment with trandolapril-verapamil significantly
      improved left ventricular function. In a double-blind randomized study of 100
      postinfarct patients with congestive heart failure the cardiac event rate was
      significantly lower in verapamil-trandolapril-treated than in the trandolapril
      treated patients. These results indicate that the combined treatment with
      verapamil and trandolapril might be beneficial in patients with ischaemic heart
      disease and congestive heart failure.

PMID- 9534102
TI  - Compliance, electronic monitoring and antihypertensive drugs.
AB  - Hypertension, even of mild-to-moderate severity, is undoubtedly a risk factor for
      cardiovascular morbidity and mortality. It has been well demonstrated, in
      numerous studies that have been subjected to meta-analysis, that the introduction
      of antihypertensive treatment leads to reductions in cardiovascular and
      cerebrovascular events. These results can be obtained with even a moderate
      reduction in blood pressure, of the order of 4-5 mmHg in diastolic blood
      pressure. However, many studies have shown that the percentage of treated
      hypertensive individuals who have a reduction in blood pressure to normal values
      of systolic blood pressure/ diastolic blood pressure (< 140/90 mmHg) is of the
      order of 30%. The reduction in blood pressure data are well correlated with the
      level of compliance. This compliance can be defined as the adherence by the
      patient to the directions given by the doctor for medication dosage, and this can
      be considered as 'good' when it is of the order of 80%. Until recently the
      examination of compliance relied on questioning the patient, pill counts or
      ultimately blood sampling for drug levels, which could be used only in research.
      The use of an electronic pill box with a microprocessor in the cover that records
      the date and hour each time the box is opened is a precise method of recording
      compliance. The purpose of such a method is to study overall compliance, which
      deteriorates as time passes and falls by approximately 50% after 1 year. However,
      this compliance can be modified and improved if instruction and follow-up are
      given to the patient. Prescription compliance can be improved by once daily
      dosing and by instructing for this to be taken in the morning. In contrast
      compliance is considerably reduced when more than two doses are to be taken each
      day. Using the pill counting box allows us to describe and focus on different
      types of patients, ranging from rigidly adherent to completely chaotic. It seems
      that factors such as age and activity can influence these patterns of compliance.

PMID- 9534103
TI  - Fixed drug combinations in the treatment of hypertension: how to identify the
      optimal dose.
AB  - RATIONALE FOR DRUG COMBINATIONS: The most common reason for combining different
      drugs is to achieve an additional fall in arterial pressure. It therefore seems
      reasonable to combine drugs with different mechanisms of actions. NEED FOR
      CLINICAL TRIALS: However, the effects of combination therapy on the heart and
      other target organs remains poorly documented. Most of what we know with regard
      to combination therapy on hypertensive heart disease is based on extrapolation
      from monotherapy. The fact that two drugs when used separately are beneficial in
      a disorder does not necessarily imply that their combination is equally or more
      beneficial in the same disorder. Thus, it will become important to establish
      efficacy and safety of new drug combinations on hypertensive target organs and on
      morbidity and mortality by performing carefully designed clinical trials.

PMID- 9534104
TI  - Prevalence of cardiovascular risk factors in a French population.
AB  - STUDY ON THE IDENTIFICATION OF CARDIOVASCULAR RISK FACTORS: Identification of
      cardiovascular risk factors and the estimation of their prevalence in different
      populations is an important aim of preventive medicine. We analysed the data from
      58,803 volunteers who were subjected to systematic health examinations in the
      Centre d'Investigations Preventives et Cliniques in Paris during the period
      January 1991 to December 1993. In this report we present some results concerning
      the prevalence of the major cardiovascular risk factors and their associations
      with sex, age and the presence of hypertension. CONCLUSIONS: The present study
      clearly shows that before the age of 55 years, the prevalence of risk factors is
      higher in men than in women, whereas in postmenopausal women the risk-profile
      increases rapidly, reaching the level of men after the age of 65 years. The
      presence of multiple risk factors is much higher in hypertensive than in
      normotensive individuals. We also observed that more than two-thirds of the
      treated hypertensives had systolic/diastolic blood pressure levels of > 140/90
      mmHg. These observations could contribute to the debate regarding the evaluation
      of global risk and therapeutic strategies in cardiovascular disease prevention.

PMID- 9534105
TI  - How to treat the diabetic hypertensive individual appropriately.
AB  - ASSOCIATION OF HYPERTENSION AND DIABETES: Diabetes mellitus and arterial
      hypertension are closely related and strongly predispose an individual to
      atherosclerosis and renal failure. Hypertension is twice as frequent in diabetic
      individuals as it is in the general population, and often precedes the
      development of diabetic nephropathy. The prevalence of coexisting arterial
      hypertension and non-insulin-dependent diabetes mellitus is increasing because of
      ageing of the population, allowing an augmented prevalence of atherosclerosis and
      end-stage diabetic renal disease. ANTIHYPERTENSIVE TREATMENT OF DIABETIC
      PATIENTS: The goal of blood pressure control in diabetic patients is to reduce
      death and disability as much as possible. In addition, other reversible risk
      factors for cardiovascular disease, which are so frequently seen in hypertensive
      diabetic individuals, need to be addressed. The optimal blood pressure level in
      diabetic individuals has not yet been established, but it has been suggested that
      it be should lower than that recommended by current guidelines. In fact, the
      literature indicates that 130/85 mmHg should be the systolic/diastolic blood
      pressure goal in hypertensive diabetic individuals. According to most guidelines
      the threshold for intervention when multiple associated risk factors coexist with
      hypertension is a blood pressure level 140/90 mmHg. In diabetic patients therapy
      has to be instituted early and aggressively. In this regard, angiotensin
      converting enzyme inhibitors alone or in association with other drugs seem to be
      the best choice for hypertensive diabetic patients.

PMID- 9534106
TI  - Primary prevention of renal failure in diabetic patients: the Bergamo Nephrologic
      Diabetes Complication Trial.
AB  - BACKGROUND: Microalbuminuria is an early marker of diabetic nephropathy, and its
      prevention can be considered to be the primary prevention of diabetic
      nephropathy. Angiotensin converting enzyme inhibitors and non-dihydropyridinic
      calcium antagonists have specific renoprotective properties in diabetes, and
      preliminary evidence is available that their combination can delay the onset and
      limit the progression of nephropathy in experimental diabetes more effectively
      than either of the two agents alone. DESIGN OF CLINICAL TRIAL: The Bergamo
      Nephrologic Diabetes Complication Trial is a prospective, randomized, double
      blind, parallel-group study aimed at evaluating the possibility of preventing the
      onset of nephropathy in 2400 hypertensive non-insulin-dependent diabetes mellitus
      patients who have a normal albumin excretion rate. During phase A of the study,
      patients will be randomized to one of the following treatments for 3 years: a non
      dihydropyridinic calcium antagonist (slow-release verapamil 240 mg/day), an
      angiotensin converting enzyme inhibitor (trandolapril 2 mg/day), the combination
      of these drugs (verapamil 180 mg/day plus trandolapril 2 mg/day) and placebo.
      Other antihypertensive agents will be allowed in order to achieve and maintain
      systolic and diastolic blood pressures consistently below 140 and 90 mmHg,
      respectively, in all patients. The primary efficacy variable of phase A will be
      progression to microalbuminuria. In phase B progression to macro-albuminuria will
      be evaluated in patients who became microalbuminuric in phase A. These patients
      will be randomized to 2 years of treatment with trandolapril (2 mg/day) alone or
      combined with verapamil (180 mg/day).

PMID- 9534107
TI  - Benefits and cost of antihypertensive treatment in incipient and overt diabetic
      nephropathy.
AB  - PREVALENCE: The prevalence of abnormally elevated urinary albumin excretion rate
      (> 30 mg/24 h) is approximately 40% in insulin-dependent and in non-insulin
      dependent diabetic patients. Diabetes has become the leading cause of end-stage
      renal failure in Europe, USA and Japan. Approximately 90% of the direct and
      indirect costs of caring for diabetic patients are spent on the complications of
      diabetes. RISK FACTORS: Identification of patients at high risk of developing
      diabetic nephropathy is possible by screening for microalbuminuria (30-300 mg/24
      h). Additional risk factors/ markers for development of nephropathy are male sex,
      genetic predisposition, ethnic conditions, early onset of diabetes, poor
      metabolic control, hyperfiltration, elevated prorenin and smoking. Elevated
      urinary albumin excretion rate indicates a substantially increased cardiovascular
      morbidity and mortality risk in diabetic patients. PREVENTION OF NEPHROPATHY:
      Randomized controlled trials in normotensive insulin-dependent and in non-insulin
      dependent diabetic patients with persistent microalbuminuria indicate that
      angiotensin converting enzyme (ACE) inhibitors diminish urinary albumin excretion
      rate, and postpone and may even prevent progression to clinical overt
      nephropathy. These findings indicate that screening and intervention programs
      could probably save lives and lead to considerable economic savings. TREATMENT OF
      NEPHROPATHY: Systemic blood pressure elevation to a hypertensive level is an
      early and frequent phenomenon in diabetic nephropathy. Furthermore, nocturnal
      blood pressure elevation (non-dippers) occurs more frequently in patients with
      nephropathy. Systemic blood pressure elevation, hyperglycaemia, albuminuria and
      the D polymorphism in the ACE gene accelerate the progression of diabetic
      nephropathy. Studies of the impact of other potential progression promoters (i.e.
      smoking, hyperlipidaemia and protein intake) have yielded conflicting results.
      Effective blood pressure reduction using ACE inhibitors or drugs of other
      classes, or both, frequently in combination with diuretics reduces albuminuria,
      delays the progression of nephropathy, postpones renal failure and improves
      survival in patients with diabetic nephropathy. Antihypertensive treatment for
      diabetic nephropathy extends life and saves money.

PMID- 9534108
TI  - The roots of normalization: a reappraisal.

PMID- 9534109
TI  - Chromosomes in autism and related pervasive developmental disorders: a
      cytogenetic study.
AB  - Few studies have examined the occurrence of chromosome abnormalities in a large
      sample of patients with autism and related pervasive developmental disorders
      (PDDs). In the present report, the authors examined a consecutive series of 92
      children with PDDs (DSM-III-R; 75 males and 17 females). A cytogenetic
      examination, including growth in folate deficient medium, was performed in all
      cases. Three patients (3.2%) (two females and one male) showed chromosome
      abnormalities: deletion of the long arm of chromosome 8; tetrasomy of chromosome
      15; and XYY syndrome. Only the subject who had tetrasomy 15 met the criteria for
      autistic disorder, while the other were diagnosed as suffering from a PDD not
      otherwise specified (PDDNOS). Another patient showed an abnormal fragile site at
      Xq27 in three out of 100 cells. However, subsequent molecular studies did not
      confirm the presence of fragile-X syndrome. These results suggest that chromosome
      abnormalities are uncommon in traditional autism and may be relatively more
      common in people with PDDNOS.

PMID- 9534110
TI  - Visual behaviour and dyadic interaction between people with intellectual
      disability and people who are non-disabled.
AB  - Patterns of visual dominance in human interaction have been studied by a number
      of authors. The purpose of the present research was to investigate the
      implications of these studies for interaction between people who are disabled and
      people who are non-disabled. It was predicted that disability would differentiate
      the two groups, with non-disabled partners dominating the visual interaction. Two
      studies are reported. The first looked at visual interaction through the two
      looking modes of looking while listening and looking while speaking between 16
      dyads where one partner was intellectually disabled and the other non-disabled.
      In the second study, eight subjects who were intellectually disabled and who had
      participated in the first study interacted with another person who had an
      intellectual disability. Their looking modes were then compared between
      conversing with a non-disabled partner in study 1 and with those of their partner
      with intellectual disability in study 2. The outcome of the studies showed that
      subjects who were intellectually disabled did not discriminate in looking mode
      between partners of different intellectual levels. Conversely, subjects who were
      non-disabled spoke and looked significantly more when conversing with their
      partner who was intellectually disabled. It has been argued that overlooking and
      overspeaking could arise from the need for the non-disabled person to gain some
      sign of affiliation from their partner, or alternatively, that it might reflect a
      dominant non-disabled person attempting to facilitate a cooperative style.

PMID- 9534111
TI  - A reliability study of the Spanish version of the social behaviour schedule (SBS)
      in a population of adults with learning disabilities.
AB  - The reliability of the Spanish version of the Social Behaviour Schedule (SBS) was
      tested in a vocational setting on a sample of 64 subjects with learning
      disabilities. Test-retest assessment showed a good percentage of agreement (80%)
      and adequate kappa values for most SBS items. The overall percentage of agreement
      of inter-rater reliability was 85% and kappa values were moderate to nearly
      perfect for 52% of items. Inter-informant analyses produced poorer results, with
      an average agreement of 43% and inadequate kappa values on 42% of items. The
      intraclass correlation coefficient (ICC) was 0.64 for test-retest, 0.76 for inter
      rater assessment and 0.94 for inter-informant assessment. The Spearman
      correlation coefficient was adequate on the test-retest and inter-rater analyses,
      but not on inter-informant analysis. This low inter-informant agreement could be
      attributed to environmental factors which alter the reliability of reports from
      different informants in community settings with high levels of normalization. In
      such environments, an interview with a key informant may not suffice, and both a
      careful review of the clinical record and a direct interview with subjects may
      enhance the reliability of the information attained.

PMID- 9534112
TI  - Cooperative learning and social acceptance of children with mild intellectual
      disability.
AB  - The effects of the participation of non-disabled children in a cooperative
      learning programme on their social acceptance of classmates with mild
      intellectual disability was examined. A sample of 24 children with mild
      intellectual disability in the 9-11-year-old age-range was identified from
      educational psychologists' case records. All of the children were receiving
      mainstreaming special education programmes at the time of the study. Twelve of
      the children had previously attended special education classes, while the
      remainder had always attended regular classes. Half of the children's regular
      classes were randomly assigned to either receive an experimental cooperative
      learning programme or to serve as control classrooms. The non-disabled children
      in the experimental classes showed significant increases in their social
      acceptance (sociometric ratings) of the children with mild intellectual
      disability, both immediately following the programme and 5 weeks later, but no
      such increases were evident in the children in the control classrooms. This
      pattern held for both the former special class pupils and the children with mild
      intellectual disability who had never attended special classes. The results
      confirm the usefulness of cooperative learning strategies for enhancing the
      social acceptance of children with mild intellectual disability in mainstreaming
      special educational programmes, regardless of the nature of their previous
      special educational provisions.

PMID- 9534113
TI  - Staff:staff and staff:client reliability of the Schalock & Keith (1993) Quality
      of Life Questionnaire.
AB  - A small-scale study of the inter-rater and staff:client reliability of the
      Schalock & Keith (1993) Quality of Life Questionnaire (QOL-Q) was conducted.
      Whilst the sample size was small and the QOL-Q achieved an acceptable overall
      level of reliability, the study replicated the pattern of low staff:client
      concordance and staff overestimation of the independence and autonomy of clients
      reported by Reiter & Bendov (1996). The results are briefly discussed in the
      context of the ongoing debate about the utility of proxy response in the
      literature.

PMID- 9534114
TI  - Clumsiness in autism and Asperger syndrome: a further report.
AB  - Clumsiness has been proposed as a diagnostic feature of Asperger syndrome (AS), a
      type of pervasive developmental disorder recently introduced in the ICD-10 and
      DSM-IV. However, the extent to which this symptom is specific to AS is not clear.
      To investigate this issue, we compared a sample of AS children with age- and sex
      matched groups of children with autistic disorder and pervasive developmental
      disorder not otherwise specified (PDDNOS). Twelve subjects with AS (ICD-10/DSM
      IV; 11 males; average age 11.4 years; mean full-scale IQ 104.9) were compared
      with 12 subjects with autistic disorder (DSM-III-R; II males; average age 10.3
      years; mean full-scale IQ 78.4) and 12 subjects with PDDNOS (DSM-III-R; 10 males;
      average age 10.1 years; mean full-scale IQ 78.2). The BruininksOseretsky test, a
      standardized test of motor coordination, was administered blind by the same
      investigator to all the three groups. While coordination deficits were found in
      all three groups, children with AS were found to be less impaired than those with
      autistic disorder and PDDNOS. However, no significant relationship was found
      between coordination scores and diagnosis after adjusting for the level of
      intelligence. These findings suggest that some patients with AS may be less
      clumsy than those with autistic disorder and that this difference may be the
      result of their higher level of intelligence. Studies based on larger samples
      using multiple measures of coordination are needed to further clarify the role of
      clumsiness in the classification of pervasive developmental disorders.

PMID- 9534115
TI  - Antipsychotic medication, psychiatric diagnosis and children with intellectual
      disability: a 12-year follow-up study.
AB  - This study is a follow-up to an original survey carried out in the early 1980s of
      all children with an identified intellectual disability in Cornwall, England. The
      purpose of this second study was to review the use of antipsychotic medication in
      these children and to relate it to their various diagnoses. This is a relatively
      under-researched area, and the few comparable studies in children have not been
      designed to specify diagnoses, psychiatric or otherwise. A positive relationship
      between the diagnosis of autistic spectrum disorders in children and the use of
      antipsychotic medication was one of the important findings which emerged from the
      research. The possible reasons for this association are discussed.

PMID- 9534116
TI  - Rewards and gratifications among family caregivers: towards a refined model of
      caring and coping.
AB  - Supplemented by a case illustration, findings from a study in Wales are reported
      for the first time from the application of two new instruments for measuring
      rewards and stresses among family caregivers. The paper takes as its starting
      point a critique of models of caregiving which emphasize instrumental and
      pathological dimensions. Findings suggest that caregivers report the existence of
      pervasive rewards and gratifications, as well as stresses, as part of the
      caregiving experience, and that these stem from varying sources. The role of
      rewards and satisfactions in stress-coping models is briefly discussed, and
      implications for changed practice and policy thinking are reviewed.

PMID- 9534117
TI  - The development of a self-report measure to assess the location and intensity of
      pain in people with intellectual disabilities.
AB  - The performance of a target group of 20 people with intellectual disability (ID)
      and a comparison group of 20 people who did not have ID was investigated on a
      series of tasks involving the judgement of the location of pain (on a bodymap)
      and the intensity of pain (on an analogue colour scale) in response to a series
      of photographs of simulated painful experiences. The results of the study
      indicated that: (1) there were no differences between the target and comparison
      groups in judging pain location for 93% of test items; (2) the performance of the
      target group in judging pain location was stable over time; (3) people with ID
      rated the pain images as more intense than the comparison group on all the 'mild'
      pain stimuli and 36% of the 'severe' pain stimuli; (4) the performance of the
      target group in judging pain intensity was logically consistent for 65% of
      comparisons (clear trends towards significance being apparent for a further 10%
      of items); (5) the performance of the target group in judging pain intensity was
      stable over time; and (6) the performance of the target group was unrelated to
      indicators of cognitive ability.

PMID- 9534118
TI  - Prevalence of fragile-X syndrome and FRAXE among children with intellectual
      disability in a Caribbean island, Guadeloupe, French West Indies.
AB  - Fragile-X syndrome (FXS) is the most common cause of inherited intellectual
      disability. Although FXS has been identified in all the main ethnic groups,
      little is known about its prevalence with respect to ethnicity. Since the
      identification of the FXS primary defect, diagnosis involving DNA analysis has
      been made possible, allowing efficient screening strategies to be considered. The
      present authors have carried out FXS screening among children belonging mainly to
      the Afro-Caribbean ethnic group (163 boys and 85 girls) affected with moderate to
      severe intellectual disability of previously unknown origin. We have found a 6.7%
      and 0% prevalence among boys and girls, respectively, yielding a minimum FXS
      incidence of 0.42 per 1000 male births per year. Family studies have resulted in
      genetic counselling for several individuals. FRAXE screening was also achieved
      and no FRAXE case was detected in this study.

PMID- 9534119
TI  - The Epilepsy Outcome Scale: the development of a measure for use with carers of
      people with epilepsy plus intellectual disability.
AB  - This paper describes the development of a new scale for the assessment of
      epilepsy in people with learning disabilities. The scale was developed and
      validated in consultation with principal carers, and reflects their concerns
      about seizures, their impact and their treatment. Further testing of the scale
      revealed high internal consistency, testretest reliability and a robust factor
      structure. The scale can be completed in 5-10 min and may be useful as an outcome
      measure both in clinical practice and in research trials.

PMID- 9534120
TI  - Increased life expectancy in people with untreated phenylketonuria.
AB  - The records of 17 people with intellectual disability and untreated
      phenylketonuria (12 females and five males), who were resident in the Stoke Park
      Group of Hospitals, Bristol, England, 25 years ago, were re-examined for life
      expectancy. Six subjects had died (five females and one male). The oldest
      deceased female was 69 years of age. The average age at death was 55.8 years.
      Eleven subjects were still alive (seven females and four males). The oldest
      living male was 79 years of age. The average age of the survivors was 55.7 years.

PMID- 9534121
TI  - The social model approach to substance abuse recovery.

PMID- 9534122
TI  - An historical and developmental analysis of social model programs.
AB  - This review synthesizes the philosophy, development, history, and current status
      of the philosophy of social or community model of recovery and of Social Model
      Programs (SMPs) based on an analysis of the available literature, much of it
      outside traditional sources. The social-community model of recovery evolved out
      of Alcoholics Anonymous (AA), and has a distinctive program philosophy with
      different assumptions, knowledge, and practice than professionally based
      treatment models. SMPs began in the 1940s in California, evolving by the 1980s
      into a continuum of recovery services that are publicly funded, legally
      incorporated nonprofit organizations. The characteristics of SMPs are described
      and the range of services are presented, including social setting detoxification,
      residential recovery homes, non-residential neighborhood recovery centers and
      sober living houses. SMPs are staffed exclusively by recovering alcoholics and
      their structure is based on the 12 traditions of AA, which emphasize democratic
      group processes with shared and rotated leadership and a minimal hierarchy. Cost
      effectiveness data suggest that residential social model programs average
      approximately $2,700 per stay versus $4,400 for other residential approaches, yet
      may offer similar outcomes in terms of substance use and improvement employment
      or family function.

PMID- 9534123
TI  - Methodology and characteristics of programs and clients in the social model
      process evaluation.
AB  - A process evaluation of social model residential substance abuse programs was
      conducted by the Alcohol Research Group (ARG) from September 1995 to April 1996.
      This paper first describes the qualitative protocol used in that study, including
      site selection, rules for observation, and the grounded theory approach taken to
      data analysis. Overviews of the programs offered at each study site are given,
      including overall philosophy, staffing approach, size of program, length of stay,
      funding sources and cost for average stay. Using survey data available from
      another ARG study, background demographic and Addiction Severity Index client
      level information are presented to augment the program level results of the
      process evaluation.

PMID- 9534124
TI  - Measuring treatment philosophy: a scale for substance abuse recovery programs.
AB  - The assessment of the philosophy that guides substance abuse treatment programs
      has been a difficult subject to approach by those working in treatment research.
      Differing treatment philosophies are generally represented by multi-dimensional
      theoretical constructs that do not easily lend themselves to assessment by
      quantitative means. In the U.S., substance abuse treatment programs have been
      suggested as fitting into a disease (or medical) model, a social learning (or
      psychological) model, or a social community model in designing a treatment regime
      for clients. This paper presents a Social Model Philosophy Scale (SMPS) to
      classify the extent to which a given treatment program follows a social model
      approach to treatment. The final version of the SMPS (available from the first
      author) contains 33 questions for use in residential programs, divided into six
      conceptual domains: physical environment, staff role, authority base, view of
      substance abuse problems, governance, and community orientation. Overall internal
      reliability is high (alpha = .92), with subscale alphas ranging between .57 and
      .79. Test-retest analyses showed that the information obtained from the SMPS is
      consistent across time, administrators, and respondents. In addition, the SMPS is
      brief and easy to administer. Methodology used in item creation and final item
      selection is reported. Although not designed to distinguish philosophies other
      than social model, early results suggest that the SMPS may also be used to
      classify other program philosophies.

PMID- 9534125
TI  - Is recovery planning any different from treatment planning?
AB  - Using process evaluation data, this paper compares the "recovery" planning
      process of the social model programs with the "treatment" planning process in a
      comparison medical model program. We consider how the planning process is
      actually conducted, the role of staff versus clients in the planning process, and
      how the implementation of the planning process is monitored and evaluated at the
      programs. Results point to major differences in the actual process of treatment
      planning and recovery planning. Professional staff at medical model programs
      generally direct and control the planning process and its implementation. In
      social model programs, clients are directly responsible for developing their own
      recovery plans, within a context of help from peers and recovering staff; the
      latter oversee the process. We conclude that both treatment planning and recovery
      planning are distinct and defining features of medical and social model
      philosophies. Treatment planning in medical model programs and recovery planning
      in social model programs serve similar administrative and programmatic functions.
      However, the impact on patients/residents is likely to be significantly
      different. Recovery planning becomes a skill acquired by clients, part of the
      experiential education characterizing social model programs. Future research is
      needed to assess whether these planning skills actually aid social model clients
      in structuring a sober lifestyle in aftercare, and whether differences are
      obtained by the more passive client role in planning taken at the medical model
      program.

PMID- 9534126
TI  - Didactic and experiential education in substance abuse programs.
AB  - Medical model and social model programs both include client education as part of
      their service mandate, although the two models may define and accomplish the task
      of education differently. The role of education in substance abuse recovery has
      not been clear in either the treatment or recovery models. This paper therefore
      begins with a debate of the value of "educating" substance abuse clients, using
      several possible definitions of education and drawing upon a variety of theories
      from health education and community psychology. We divide these types of
      education into two broad definitional categories: knowledge acquisition and life
      skills development. Using data collected during a process evaluation at one
      medical and two social model programs, we provide examples of how knowledge
      acquisition and life skills development are accomplished at these sites. Analysis
      of the observational data pointed to two approaches to education, one didactic,
      the other experiential. All three sites used a didactic approach to knowledge
      about addiction. Only the social model sites used an experiential approach to
      convey knowledge and skills about recovery, and the development of life skills.

PMID- 9534127
TI  - The community orientation of social model and medical model recovery programs.
AB  - This paper examines the extent to which two social model programs and one medical
      model program operating in the same county were able to establish links between
      their programs and the community at large. Emphasis on community and environment
      is a hallmark of social model programs, suggesting that more effective links will
      have been established at those programs than at the medical model program. Items
      from the community orientation subscale of the Social Model Philosophy Scale
      provide a guide for this qualitative analysis. Community resources considered
      include self-help 12-step programs, as well as community agencies chartered to
      address employment, education, family counseling, and housing. All three programs
      were found to have a strong emphasis on Alcoholics Anonymous (AA)/Narcotics
      Anonymous (NA). At the medical model program (MMP), patients were exposed to
      three to five AA or NA meetings per week during their 10-day stay, although for
      the most part, meetings in the MMP had few, if any, outsiders. The social model
      programs exposed residents to a number of different AA and NA meetings, both at
      the program and in the community over a period of months. The MMP program was
      found to have minimal links with the community for employment, education, or
      other services. The MMP program counselors did try to make referrals to other
      substance abuse programs upon release from the hospital, and to insure that
      patients had somewhere to go for shelter after being discharged. In contrast,
      social model programs encouraged residents to utilize community resources for
      health, education, and social service needs.

PMID- 9534128
TI  - Work and identity in substance abuse recovery.
AB  - Reduction in length of stay due to managed care has forced medical model
      treatment to focus on detoxification and "medically necessary" services at the
      expense of "wraparound" social services addressing employment, housing, and
      family problems. Lower staff and infrastructure costs enable social model
      programs to offer more (nonmedical) services and a longer stay at comparatively
      lower cost. Among the services they provide are vocational rehabilitation and job
      search training, with the view that participants are better off if re-entry is
      mediated by sober social networks, stable environments, and employment. This
      paper demonstrates that employment training/job search activities are integrated
      into social model programs, and offers qualitative evidence of how staff and
      advanced residents teach the value of work. Longitudinal quantitative data
      collected at the same time suggest the focus of social model on employment does
      make a difference in posttreatment functioning: 1-year follow-up Addiction
      Severity Index (ASI) scores show decreases in employment problems among social
      model clients, along with comparable improvement on other composite scores of the
      ASI.

PMID- 9534129
TI  - [Treatment of low-grade gastric MALT lymphoma with Helicobacter pylori
      eradication. Follow-up of the histological and molecular response].
AB  - BACKGROUND: Low grade gastric MALT lymphoma is associated to infection with
      Helicobacter pylori. Also, H. pylori eradication can produce histologic
      regression of the lymphoma. PATIENTS AND METHODS: This study reports the follow
      up of a prospective series of 11 patients with low grade gastric MALT lymphoma,
      stage I, treated with eradicative therapy for H. pylori. After treatment,
      patients were followed up with sequential endoscopies to asses the histological
      and molecular regression of the lymphoma, using a score of the histological
      lesions and the amplification of the IgH gene with PCR analysis. RESULTS:
      Helicobacter pylori was eradicated in all patients. In 10(90.9%) histological
      regression of the lymphoma was demonstrated, in 6 of them in the first control
      after treatment. In the 10 patients with histological response, PCR analysis
      demonstrated a polyclonal rearrangement of the IgH gene in 6 (60%) and a clonal
      band in 4 (40%), that eventually disappeared at 12 (SD 4) months after treatment.
      In 4 patients with a previous polyclonal rearrangement, a clonal band was
      occasionally detected in any sequential controls; in 2 of these cases the clonal
      band disappeared 5 and 7 months after treatment and in the remaining 2 its
      evolution is not yet known. Nine patients have been followed up and are in
      remission 18 (SD 8) months after treatment. CONCLUSIONS: Eradication of H. pylori
      can produce histologic regression in stage I low grade gastric MALT lymphoma, and
      should be the first therapeutic option. Despite histological regression of the
      lymphoma, PCR analysis can detect a clonal rearrangement of the IgH gene in 40%
      of the cases, but its significance remains unknown. Sequential and prolonged
      follow-up is essential to assess whether this lymphoma can be actually cured with
      eradication therapy for H. pylori.

PMID- 9534130
TI  - [Is gastric lymphoma an infectious disease?].

PMID- 9534131
TI  - [Hepatitis G virus, agent responsible fo hepatitis or is it an innocuous virus?].

PMID- 9534133
TI  - [Grammatical problems in medicine].

PMID- 9534134
TI  - [Intrafamilial transmission of the hepatitis C virus].

PMID- 9534135
TI  - [Influence of anxiety in the tolerance of upper digestive endoscopy].

PMID- 9534136
TI  - [Mortality pattern of persons under the age of 25 years].

PMID- 9534137
TI  - [Hemolytic uremic syndrome and diagnosis of infection by enterohemorrhagic
      Escherichia coli].

PMID- 9534138
TI  - [Heart rate variability during the first 24 hours of acute myocardial
      infarction].
AB  - BACKGROUND: To evaluate the heart rate variability (HRV) during the first 24 h
      after a myocardial infarction (MI), and to study its relationship with other
      clinical variables and in-hospital follow-up. PATIENTS AND METHODS: 101 patients
      (age < 80 years) with MI in sinus rhythm were prospectively studied. A Holter
      monitoring was performed during the first 24 h. The heart rate (HR), standard
      deviation of RR intervals (SDRR) and the histogram at different levels were
      analyzed, as well as the mean and standard deviation of RR intervals in an early
      5 min record. The results were compared with the clinical characteristics and the
      in-hospital outcome of the patient. RESULTS: HRV was lower in women,
      hypertensives and patients who did not receive thrombolytic agents. In patients
      without heart failure, inferior MI's had lower HR and higher HRV than anterior
      MI's (SDRR: 52.8 [20.6] and 42.2 [16.9], respectively; p < 0.05). HRV was
      significantly decreased as Killip group increased, as well as in patients who
      developed late heart failure. The development of ventricular tachycardia or
      fibrillation was associated to a low HRV in the 24 h analysis (SDRR: 30.2 [15.6]
      for the 6 patients with VF/VT vs 46.8 [20.1] for the rest; p < 0.05), as well as
      in the early 5 min record (29.8 [14.8] and 50.8 [35.8], respectively; p < 0.05).
      CONCLUSIONS: During the first 24 h after MI the HRV is related to some clinical
      variables and to MI location (higher in inferior MI). Patients who develop heart
      failure or ventricular arrhythmias before hospital discharge have a higher HR and
      a significantly decreased HRV.

PMID- 9534139
TI  - [Risk of developing and dying from cancer in Catalonia, Spain].
AB  - BACKGROUND: Cumulative risk reflects the lifetime probability that a person will
      develop a disease or will die from a disease. In this paper we estimate the
      cumulative risk of developing cancer and dying from cancer during the period 1988
      1992 in Catalonia (Spain). MATERIAL AND METHODS: Data from the Tarragona Cancer
      Registry and Catalonia Mortality Registry are used. Cancer incidence from
      Tarragona is extrapolated to the total Catalan population. Cumulative risk is
      estimated from cumulative rate and with a life table method, which takes into
      account competing risks. The change in risk with age is also studied. RESULTS:
      Lifetime risk of developing cancer in Catalonia is 38.9% for men and 28.0% for
      women. Risk of dying from cancer is 26.3% for men and 17.2% for women, that is, a
      67.6% and a 61.5% of incident cases, respectively. One in 14 men will develop
      lung cancer and nearly all of them will die from the disease. One in 14 women
      will develop breast cancer and 45% of them will die from the disease. CONCLUSION:
      Cancer is an important health problem in Catalonia because its high impact at the
      individual level shown by the cumulative risk. More than one in 3 men and one in
      4 women are diagnosed of cancer during their lives and, among them, two thirds
      die because the disease.

PMID- 9534140
TI  - [Cytogenetic study of 93 myelodysplastic syndromes].
AB  - BACKGROUND: We describe the cytogenetic results of 93 patients with
      myelodysplastic syndromes (MDS). The main object of this report is to analyze the
      prognostic value of the karyotype in patients with MDS, in relation to the
      evolution to acute leukemia and the survival time. PATIENTS AND METHODS:
      Cytogenetic studies were performed in 93 untreated cases of MDS between 1985 and
      1994. Overall survival and the evolution to acute leukemia were analyzed.
      RESULTS: Among 93 patients who were examined at the time of diagnosis, 40 had an
      abnormal karyotype (43%). The highest frequency of chromosome abnormalities was
      observed in refractory anaemia with excess of blasts (RAEB) (65.7%) and RAEB in
      transformation (RAEB-t) (40%) and the lowest in refractory anaemia with ringed
      sideroblasts (RARS) (10%). The chromosomes most frequently involved were: 5, 7,
      8, 11, 12 and 17. No relationship was found between FAB subtypes and the type of
      chromosomal abnormalities. In respect to the prognosis, an abnormal karyotype,
      and a complex karyotype were related with a higher frequency of evolution to
      acute leukemia. A model based on karyotype could divide patients in two groups:
      poor prognosis (patients with an abnormal karyotype, with involvement of
      chromosome 7, trisomy 8 or with a complex karyotype), and a good prognosis
      (patients with normal karyotype). CONCLUSIONS: The cytogenetic studies are very
      useful in the study of MDS for their clinical implications.

PMID- 9534141
TI  - [Risk of developing and dying from cancer: a lost war?].

PMID- 9534142
TI  - [Risk factors for ischemic heart disease in the elderly].

PMID- 9534143
TI  - [Let's talk about microbes].

PMID- 9534144
TI  - [Esophageal ulcer due to doxycycline].

PMID- 9534145
TI  - [Esophagitis associated with 750 mg amoxicillin tablets].

PMID- 9534146
TI  - [Prevalence of oral lesions diagnosed in a group of intravenous drug addict
      prisoners with AIDS and their correlation with CD4 lymphocyte count].

PMID- 9534147
TI  - Protein folding and assembly in a cell-free expression system.

PMID- 9534148
TI  - Preparation and application of chaperone-deficient Escherichia coli cell-free
      translation systems.

PMID- 9534149
TI  - Protein disulfide isomerase.

PMID- 9534150
TI  - Thermophilic fungal protein disulfide isomerase.

PMID- 9534151
TI  - Disulfide bond catalysts in Escherichia coli.

PMID- 9534152
TI  - Yeast immunophilins: purification and assay of yeast FKBP12.

PMID- 9534153
TI  - Peptidylprolyl cis-trans-isomerases from plant organelles.

PMID- 9534154
TI  - Purification of GroEL with low fluorescence background.

PMID- 9534155
TI  - Overexpression, purification, and properties of GroES from Escherichia coli.

PMID- 9534156
TI  - Criteria for assessing the purity and quality of GroEL.

PMID- 9534157
TI  - Construction of single-ring and two-ring hybrid versions of bacterial chaperonin
      GroEL.

PMID- 9534158
TI  - Chaperonin 60(14) and co-chaperonin 10(7) from Chromatium vinosum.

PMID- 9534159
TI  - Chaperonins of the purple nonsulfur bacterium Rhodobacter sphaeroides.

PMID- 9534160
TI  - Chaperonins from Thermoanaerobacter species.

PMID- 9534161
TI  - Chaperonin from thermophile Thermus thermophilus.

PMID- 9534162
TI  - Insect chaperonin 60: symbionin.

PMID- 9534163
TI  - Purification of yeast mitochondrial chaperonin 60 and co-chaperonin 10.

PMID- 9534164
TI  - Purification of mammalian mitochondrial chaperonin 60 through in vitro
      reconstitution of active oligomers.

PMID- 9534165
TI  - Purification of recombinant plant and animal GroES homologs: chloroplast and
      mitochondrial chaperonin 10.

PMID- 9534166
TI  - Mammalian cytosolic chaperonin.
AB  - Cytosolic chaperonin, the eukaryotic cytosolic homolog of GroEL, has certain
      unusual features that make it uniquely useful for studying the mechanism of
      chaperonin action. It is of particular interest as an essential component in the
      generation of native actin and tubulin in vivo. We describe a method for the
      purification of mammalian c-cpn from rabbit reticulocyte lysate via a three-step
      procedure involving ion-exchange chromatography, affinity selection on ATP
      agarose, and gel filtration. We also describe a sensitive in vitro-folding assay
      for the activity of c-cpn and other chaperone proteins, and a simple
      nondenaturing gel assay for the analysis of folding reaction products.

PMID- 9534167
TI  - Electron microscopy of chaperonins.

PMID- 9534168
TI  - Structural analysis of GroE chaperonin complexes using chemical cross-linking.
AB  - In this chapter, we have shown how chemical cross-linking with a bifunctional
      reagent, GA, can be used to investigate the structure of large oligomeric
      complexes such as GroEL14GroES7 and GroEL14(GroES7)2. Cross-linking, followed by
      denaturing electrophoresis, confirmed the number and arrangement of GroEL and
      GroES subunits within each individual oligomer, which was previously known from
      EM analysis. Furthermore, cross-linking permitted a close examination of the
      effect of regulatory factors, such as nucleotides and free divalent cations, on
      the molecular structure of GroEL14, GroEL14GroES7, and GroEL14GroES7. Finally,
      cross-linking analysis permitted characterization and quantitation of various
      chaperonin heterooligomeric complexes, GroEL14, GroEL14GroES7, and GroEL14GroES7
      in solution, under conditions that also supported protein folding and ATP
      hydrolysis. It was shown that GA does not induce the artifactual association or
      the dissociation of GroES7 from the chaperonin. On the contrary, chemical cross
      linking is an obligatory procedure when the subsequent analysis is carried out
      using methods that can displace the equilibrium.

PMID- 9534169
TI  - Molecular chaperones and their interactions investigated by analytical
      ultracentrifugation and other methodologies.

PMID- 9534170
TI  - Probing conformations of GroEL-bound substrate proteins by mass spectrometry.

PMID- 9534171
TI  - Fluorescence anisotropy method for investigation of GroEL-GroES interaction.

PMID- 9534172
TI  - Photoincorporation of fluorescent probe into GroEL: defining site of interaction.
AB  - We have elucidated conditions for the covalent incorporation of a nonspecific
      hydrophobic probe, bisANS, into various proteins. Using this method, we are able
      to map hydrophobic surfaces in proteins. In addition, we have shown that for
      GroEL, we are able to use the fluorescence of the incorporated bisANS to monitor
      conformational changes in a defined region of the protein in response to various
      effectors. This method should be useful for studying both protein structure and
      dynamics.

PMID- 9534173
TI  - Analysis of chaperone function using citrate synthase as nonnative substrate
      protein.

PMID- 9534174
TI  - Purification and characterization of small heat shock proteins.

PMID- 9534175
TI  - Expression, purification, and molecular chaperone activity of plant recombinant
      small heat shock proteins.

PMID- 9534177
TI  - Purification and properties of BiP.

PMID- 9534176
TI  - Lens alpha-crystallin: chaperone-like properties.

PMID- 9534178
TI  - Purification and characterization of prokaryotic and eukaryotic Hsp90.

PMID- 9534179
TI  - Purification of Hsp90 partner proteins Hop/p60, p23, and FKBP52.

PMID- 9534180
TI  - Purification and properties of Hsp104 from yeast.

PMID- 9534181
TI  - SecB: a chaperone from Escherichia coli.

PMID- 9534182
TI  - Expert calls for new concepts of race in cancer studies.

PMID- 9534183
TI  - Cultural factors as important as cost in diet choices among poor.

PMID- 9534184
TI  - Fatigue in cancer and HIV/AIDS.
AB  - Fatigue is a common and troubling symptom in patients with cancer or HIV/AIDS,
      resulting in significant disability and adverse effects on quality of life. Its
      etiology remains complex and is most likely multifactorial. Despite its impact
      and prevalence, fatigue is often overlooked and undertreated in these patient
      populations. The general perceptions of fatigue are that its etiology cannot be
      determined, it is an inevitable manifestation that must be endured, and few
      interventions are available. Efforts are ongoing to better understand the
      etiology, characteristics, and consequences of fatigue in patients with cancer or
      HIV/AIDS. New practical methods of assessing it in cancer patients are now
      available. In order to improve the quality of life in these patients, physicians
      need to reassess their perceptions of fatigue and their approach to its diagnosis
      and management. There are recognizable causes and correlates for which
      interventions can be beneficial. These include anemia, pain, infection/fever,
      hormonal or nutritional deficiencies, depression/anxiety, sleep disturbances, and
      excessive inactivity or rest. Physicians should fully evaluate patients to
      identify the factors amenable to management. Fatigue is also seldom discussed by
      patients and their physicians. Improved communication with and counseling of
      patients and their caregivers can play an important role in the effective
      assessment and management of fatigue in patients with cancer or HIV/AIDS. Many
      patients may benefit from wider implementation of recent advances in the
      understanding and treatment of fatigue in these oncologic and infectious
      conditions.

PMID- 9534185
TI  - Would oncologists want chemotherapy if they had non-small-cell lung cancer?

PMID- 9534188
TI  - Combined radiation and chemotherapy for carcinoma of the anal canal.
AB  - Sphincter-preserving treatment with combined radiation and chemotherapy has
      replaced abdominoperineal resection as the standard of care for patients with
      carcinoma of the anal canal. Randomized studies have shown that the combination
      of radiation therapy, fluorouracil (5-FU), and mitomycin (Mutamycin) is superior
      to radiation alone or to radiation combined with 5-FU in these patients and that
      the colostomy-free survival rate is 71%. Research is underway to determine
      whether other combinations, such as higher doses of radiation with 5-FU and
      cisplatin (Platinol), will result in lower or equivalent toxicity or better
      locoregional control and potentially improved survival. Currently, radiation
      combined with 5-FU and mitomycin remains the treatment of choice in most patients
      with carcinoma of the anal canal.

PMID- 9534189
TI  - Clinical trials referral resource. Children with brain tumors.

PMID- 9534190
TI  - Molecular genetics of hereditary ovarian cancer.
AB  - Approximately 10% of all epithelial ovarian carcinoma cases are associated with
      inheritance of an autosomal-dominant genetic mutation conferring a predisposition
      to cancer with variable penetrance. Two such manifestations of hereditary ovarian
      cancer are currently recognized: the breast and ovarian cancer syndrome and the
      hereditary nonpolyposis colorectal cancer (HNPCC) syndrome. The breast and
      ovarian cancer syndrome is linked to the BRCA1 gene on chromosome 17q and, to a
      lesser extent, to the BRCA2 gene on chromosome 13q. The HNPCC syndrome is caused
      by any one of three known genes, hMSH2, hMLH1, and hPMS2, that encode proteins
      involved in the same pathway of DNA mismatch repair. Genetic screening for germ
      line transmission of a defective allele of these genes is now possible for high
      risk individuals. Despite the rapid pace of research advances in this area,
      however, considerable uncertainties remain regarding factors that affect the
      penetrance and tissue-specific expressivity of these mutations. Current research
      challenges include elucidating these modifying factors, gaining a better
      understanding of the biological function of BRCA1 and BRCA2 products, and
      determining the appropriate clinical intervention for genetically predisposed
      patients.

PMID- 9534191
TI  - Dignified death not common, doctors and nurses say.

PMID- 9534192
TI  - 'Political action' urged to counter growing lung cancer threat to women.

PMID- 9534193
TI  - Radiologic diagnosis of extrathoracic metastases to the lung.
AB  - Because many types of cancers metastasize to the lungs, early detection may
      affect both tumor staging and treatment planning. On the other hand, it is also
      important to refrain from subjecting patients to procedures that are unnecessary
      because of the low likelihood of positive yield. The radiologic modalities of
      greatest benefit in screening for pulmonary metastases are the standard chest
      radiograph and thoracic computed tomography (CT). Other modalities that may be of
      value in answering specific questions are positron emission tomography (PET) and
      magnetic resonance imaging (MRI). Factors that help determine which tests will be
      most useful in demonstrating pulmonary metastasis from extrathoracic primary
      tumors include the mechanisms of hematogenous tumor spread, the likelihood of
      distant metastasis vs spread to nearby nodal groups, and the probability of
      distant metastasis in the absence of local invasion.

PMID- 9534194
TI  - Society of Gynecologic Oncologists Clinical Practice Guidelines. Practice
      guidelines: vaginal cancer.

PMID- 9534195
TI  - Society of Gynecologic Oncologists Clinical Practice Guidelines. Practice
      guidelines: gestational trophoblastic disease.

PMID- 9534196
TI  - Health-care challenges similar for rural poor of different ethnic groups.

PMID- 9534197
TI  - Investigators involved in toremifene studies call it a potentially safer
      antiestrogen.

PMID- 9534198
TI  - Mucinous anal gland carcinoma with perianal Pagetoid spread.
AB  - We report a case of well differentiated perianal mucinous carcinoma with
      associated dysplasia of the adjacent anal gland epithelium. Anal gland dysplasia
      is only rarely demonstrable histologically in cases of adenocarcinoma of
      suspected anal gland origin. The tumor was not associated with chronic perianal
      abscess or fistula formation, which had been regarded as important in the
      pathogenesis of perianal mucinous carcinoma. There was associated, clinically
      unsuspected Pegetoid intra-epidermal spread of adenocarcinoma in the perianal
      skin.

PMID- 9534199
TI  - Immunohistochemical analysis of thyroid adenomas with Hurthle cells.
AB  - Twenty-five cases of thyroid adenomas with Hurthle cell changes, both pure and
      focal, were studied histologically and immunohistochemically with two objectives:
      first to elucidate the relationship between the normal uninvolved thyroid and the
      adenoma; and second, to evaluate the role of immunohistochemical studies in
      adenomas with Hurthle cell changes. Representative sections were stained with a
      panel of nine antibodies directed against thyroglobulin (TG), high molecular
      weight keratin (HMK), low molecular weight keratin (LMK), p53, bcl-2, epithelial
      membrane antigen (EMA), S100, carcinoembryonic antigen (CEA) and HMB45. In all
      cases, uniform strong positive staining (+3) with TG and bcl-2 was seen in the
      normal thyroid tissue while the adenoma stained moderately positive (+2). The
      reverse pattern was observed with LMK staining. Non-adenomatous thyroid cells
      were p53-negative, the majority of the Hurthle cells, however, were p53-positive
      and adenomas with an increased number of Hurthle cells had an increased
      percentage of p53 staining. The expression of EMA was variable. All thyroid cells
      both outside and within the adenoma were S100-, CEA-4 and HMB45-negative in all
      cases. The exact significance of p53 overexpression in the Hurthle cells needs
      further evaluation.

PMID- 9534200
TI  - Helicobacter pylori in ectopic gastric mucosa in Meckel's diverticulum.
AB  - We report a case of a 25-year-old man who presented with a large rectal bleed and
      positive Meckel's scan followed by surgical excision of a Meckel's diverticulum.
      The diverticulum was lined by gastric body type mucosa showing evidence of active
      chronic gastritis associated with the presence of Helicobacter pylori organisms,
      these being identified immunohistochemically with a specific polyclonal antibody.
      We have reviewed another 21 cases of Meckel's diverticula removed at St Vincent's
      Hospital between 1984 and 1997: in nine of these cases the diverticulum was lined
      by ectopic gastric body type mucosa and in one of these there was an active
      chronic gastritis associated with Helicobacter pylori. There has been
      considerable controversy regarding both the presence and significance of
      Helicobacter organisms in Meckel's diverticula. This is the first study to use
      immunohistochemistry specifically to identify Helicobacter pylori within two
      cases of Meckel's diverticula. Both cases demonstrated an active chronic
      gastritis present within the gastric body type mucosa, thus suggesting that the
      organisms play a pathogenic role.

PMID- 9534201
TI  - Thickened gastric mucosal capillary wall: a histological marker for portal
      hypertension.
AB  - To evaluate whether the diameter or thickness of the wall of mucosal capillaries
      in the stomach could be a useful histological marker of portal hypertension,
      gastric mucosal biopsies were taken from the fundus and antrum of 73 patients
      with cirrhosis of the liver and 64 healthy volunteers. The mean +/- SD diameter
      of mucosal capillaries in the fundus of patients was not significantly different
      from that in the control group (59.4 +/- 16.8 microns vs 53.5 +/- 16.5 microns,
      respectively; P = NS). However, the mean +/- SD diameter of the antral mucosal
      capillaries was significantly greater in patients compared to controls (61.3 +/-
      18.1 microns vs 47.6 +/- 12.7 microns, respectively; P < 0.001). The mean +/- SD
      thickness of the fundal and antral capillary wall in the patients group (6.8 +/-
      2.4 microns and 7.2 +/- 2.4 microns, respectively) was significantly greater than
      that in the control group (3.5 +/- 1.5 microns and 3.3 +/- 1.5 microns,
      respectively) (P < 0.001 for each). The overall diagnostic accuracy of antral
      mucosal capillary diameter to diagnose portal hypertension was 50%, while that of
      thickened fundal and antral mucosal capillary wall was 84% and 85%, respectively.
      It is concluded that the gastric mucosal capillary walls are thicker in patients
      with portal hypertension and that this is a more reliable histological marker of
      portal hypertension than dilated gastric mucosal capillaries.

PMID- 9534202
TI  - Soft tissue Rosai Dorfman disease mimicking inflammatory pseudotumor: a
      diagnostic pitfall.
AB  - Rosai Dorfman disease, or sinus histiocytosis with massive lymphadenopathy
      (SHML), may be a difficult diagnosis to make, especially in extranodal sites.
      With soft tissue involvement the characteristic diagnostic features of large
      histiocytic cells with emperipolesis may be overshadowed by a fibroinflammatory
      component. In these cases it is easy to confuse this lesion with reactive nodules
      and benign and malignant neoplasms. We report a case in which soft tissue SHML
      was confused with an inflammatory pseudotumor. Only after review, when other
      extranodal sites became apparent, was the correct diagnosis made. Pitfalls in the
      diagnosis of soft tissue SHML are discussed.

PMID- 9534203
TI  - Broadsheet number 42: prostate specific antigen update.

PMID- 9534204
TI  - Endothelial activation and cytokine expression in human acute cardiac allograft
      rejection.
AB  - By extrapolation from the responses of cultured human umbilical vein endothelial
      cells (EC) and bovine aortic EC to short-term cytokine stimulation, EC activation
      is postulated as a likely component of the host response in acute allograft
      rejection and cardiac transplant-associated accelerated arteriosclerosis. To
      investigate the extent to which EC activation occurs in vivo in humans and to
      identify potential targets for therapeutic interventions, we compared the
      phenotypic characteristics of vascular EC as seen during clinicopathologically
      significant vs non-significant acute cardiac allograft rejection. We used
      monoclonal and monospecific polyclonal antibodies to coagulation molecules
      [tissue factor, thrombomodulin (TM), antithrombin III (AT-III),
      fibrinogen/fibrin, cross-linked fibrin and von Willebrand factor (vWF)], adhesion
      molecules (P-selectin, ICAM-1) and major histocompatibility complex (MHC) class I
      and II molecules. In addition we sought evidence of local cytokine production (IL
      1, IL-2R, IL-4, IL-6, IL-7, IL-8, TNF-alpha, PDGF-AA, PDGF-BB), which might
      mediate alterations in expression of these proteins. We found that in clinically
      significant grades of cardiac allograft rejection requiring increased
      immunosuppression, in contrast to lesser grades of rejection not requiring
      clinical intervention, there was increased microvascular EC activation and
      differential expression of cytokines. EC changes associated with more extensive
      cardiac allograft rejection requiring treatment included: (i) disruption of the
      normal anticoagulant state with downregulation of TM and AT-III, upregulation of
      tissue factor and vWF expression, and associated extensive fibrin deposition;
      (ii) upregulation of MHC class I antigens, which are potential targets for host
      cytotoxic T lymphocytes; (iii) increased expression of the leucocyte adhesion
      molecules P-selectin and ICAM-1; (iv) expression of the pro-inflammatory
      cytokines IL-1 beta and TNF-alpha; and (v) increased expression of PDGF-AA and
      BB, which are known to promote migration and proliferation of intimal cells, and
      hence may contribute to development of transplant-associated atherosclerosis.
      Collectively these findings suggest that immune events resulting in EC surface
      changes and/or production of key cytokines play a role in the pathogenesis of
      acute transplant rejection and may contribute to the long-term complication of
      accelerated arteriosclerosis in allograft coronary arteries.

PMID- 9534205
TI  - Antithyroid and antiadrenal autoantibodies in antiglomerular basement membrane
      disease, thin basement membrane disease and Alport syndrome.
AB  - The basement membranes of the glomerulus, thyroid and adrenal all contain the
      Goodpasture antigen, the target of autoantibodies in antiglomerular basement
      membrane (GBM) disease. Antithyroid antibodies can be associated with antiGBM
      disease, and there have been occasional reports of antithyroid antibodies in
      Alport syndrome, an inherited kidney disease where the GBM lacks the Goodpasture
      antigen. The aim of this study was to determine how often antithyroid and
      antiadrenal autoantibodies occurred in antiGBM disease, Alport syndrome and a
      related condition, thin basement membrane disease (TBMD). Sera from patients with
      antiGBM disease (n = 19), Alport syndrome (n = 5) or TBMD (n = 13) were tested
      for antithyroglobulin, antithyroid microsomal and antiadrenal antibodies. Five of
      the patients with antiGBM disease (5/19, 26%, P NS) had antimicrosomal, and one
      had antithyroglobulin, antibodies (1/19, 5%, P NS). No patient with Alport
      syndrome had antithyroid antibodies. One with TBMD (1/13, 8%, P NS) had
      antithyroglobulin and antimicrosomal antibodies at titres of 1/400 and 1/25,600,
      respectively. Both patients with antithyroglobulin antibodies had previously been
      diagnosed with hypothyroidism. No one with antiGBM disease, Alport syndrome or
      TBMD had antiadrenal antibodies. Antithyroid microsomal antibodies do not occur
      significantly more often in patients with antiGBM disease than in normals, and
      antithyroid and antiadrenal antibodies are not associated with Alport syndrome or
      TBMD.

PMID- 9534206
TI  - Aflatoxin exposure produces serum alphafetoprotein elevations and marked oval
      cell proliferation in young male Pekin ducklings.
AB  - Feeding of aflatoxin to ducks produces extensive oval cell proliferation in the
      liver associated with a prolonged elevation of serum alphafetoprotein (AFP).
      Short term feeding of 0.075-0.6 microgram/g of aflatoxin to young male Pekin
      ducks results in rapid and massive dose-related proliferation of "oval" cells,
      which extend from the portal zone across the hepatic lobule within three to five
      weeks. Longer term feeding of 0.15 microgram/g and 0.3 microgram/g results in
      prolonged elevations of serum AFP. Prolonged elevation of serum AFP serves as a
      marker of oval cell proliferation preceding hepatocellular carcinoma (HCC)
      development. These results confirm that ducks are sensitive to low amounts of
      aflatoxin and develop early lesions that have been shown in other studies to be
      associated with hepatocarcinogenesis. These findings in ducks support the
      likelihood that aflatoxin exposure contributes to the risk for development of HCC
      in humans.

PMID- 9534207
TI  - Matrix metalloproteinases and tissue inhibitors of metalloproteinases in giant
      cell arteritis: an immunocytochemical study.
AB  - Giant cell arteritis (GCA) is a relatively common granulomatous arteritis of
      unknown etiology which mainly occurs in elderly people. Using histopathological
      findings from-seven biopsy cases of temporal artery and one autopsy case of GCA,
      and performing immunocytochemical staining for matrix metalloproteinase (MMP)-2
      and -9 and tissue inhibitor of matrix metalloproteinase (TIMP)-1 and -2, we
      tested the hypothesis that an imbalance between MMPs and TIMPs may be a critical
      determinant in developing severe intimal hyperplasia and luminal stenosis. All
      biopsy cases revealed nearly complete luminal occlusion of the temporal artery
      with active lymphocytic infiltrate, fragmentation of internal lamina and median
      elastic fibers. Four of seven cases revealed typical GCA. The autopsy case was
      systematically sampled for histological examination, revealing GCA in the
      ascending aorta, main branches of aorta and coronary artery. Immunocytochemical
      staining revealed intense staining for MMP-2 and -9 in fragmented media of the
      aorta and artery, and less positive staining for TIMP-1 and -2 at the MMP
      positive media. In situ hybridization revealed intense positive staining for
      TIMPs in GCA despite weak immunocytochemical staining for TIMPs. Control cases
      were negative for TIMPs by immunocytochemical staining whereas RNA message level
      was mildly positive at a lesser intensity than that of GCA. Granulomatous tissue
      of fibroblasts and giant cells were most intensely positive for MMPs. The
      presence of markedly increased MMPs and less increased TIMPs in GCA may implicate
      an MMPs-TIMPs imbalance in the pathogenesis of GCA.

PMID- 9534209
TI  - Measurement of anti-dsDNA: a comparative study of two ELISA and the Crithidia
      assay.
AB  - We compared the measurement of anti-dsDNA by a commercial ELISA test (DIASTAT),
      an in-house ELISA and the Crithidia luciliae assay in cross-sectional sera
      samples of 209 systemic lupus erythematosus (SLE) patients and 64 patients with a
      variety of rheumatological, autoimmune and non-autoimmune diseases in Hong Kong.
      The Crithidia assay was found to be the least sensitive (17%) but most specific
      (95%) method for detection of a positive result in SLE patients. The DIASTAT
      assay has a higher sensitivity (68%) but lower specificity (80%) than the in
      house ELISA test (32% sensitivity and 89% specificity). The positive predictive
      value of the three assays are comparable at 90-92% while DIASTAT had the highest
      negative predictive value (44%). There was good linear correlation (r = 0.7)
      between the two ELISAs. ELISA can serve as a useful screening test for anti-dsDNA
      in SLE patients and doubtful cases can then be confirmed by another method such
      as radio-immunoassay.

PMID- 9534208
TI  - Immunodetection of the murine chemotactic protein CP-10 in bleomycin-induced
      pulmonary injury.
AB  - The murine S-100 protein designated CP-10 is a potent chemotactic factor for
      phagocytic cells, exhibiting optimal activity in the picomolar range. We assessed
      the role of this cytokine in the inflammatory response to pulmonary injury
      following intratracheal administration of bleomycin to mice. In the lungs of
      normal animals, strong cytoplasmic immunostaining for CP-10 was demonstrable in
      all recognisable neutrophil leucocytes sequestered within alveolar capillaries.
      Following induction of pulmonary inflammation in susceptible C57BL/6 mice,
      numerous CP-10-positive neutrophils were observed, but many of the recruited
      neutrophils did not exhibit staining for CP-10. No other cells were
      immunoreactive. The concentration of CP-10 in bronchoalveolar lavage (BAL) fluids
      from normal mice and mice administered intratracheal saline was below the level
      of detection by enzyme immunoassay. In contrast, nanomolar levels of CP-10 were
      detected in unconcentrated BAL fluids from C57BL/6 mice after bleomycin-induced
      injury, and the presence of monomeric CP-10 was demonstrable by Western blotting.
      Elevation of CP-10 levels correlated with the influx of inflammatory cells in
      C57BL/6 mice, but was not demonstrable in BAL fluids from BALB/c mice, which are
      resistant to pulmonary injury by bleomycin. We conclude that CP-10 may contribute
      to the recruitment of inflammatory cells in bleomycin-induced lung damage.

PMID- 9534210
TI  - Potential misidentification of Burkholderia pseudomallei by API 20NE.
AB  - Biochemical confirmation of the identity of Burkholderia pseudomallei in
      Singapore previously relied on the API 20NE panel of tests. After introducing an
      alternative proprietary biochemical panel, the Microbact 24E (MedVet, Adelaide,
      Australia), we noted that the API panel identified some presumptive B.
      pseudomallei isolates as other species. We therefore compared the performance of
      the API 20NE against the Microbact 24E with 50 distinct clinical isolates of B.
      pseudomallei, after 24 hours and after five days incubation of primary cultures.
      The API panel correctly identified 40 isolates. Four results were unacceptable or
      uninterpretable. Six isolates were misidentified as other species; the commonest
      being Chromobacterium violaceum. One of these was again identified as C.
      violaceum by the repeat API panel. Fourteen isolates, including the six
      misidentified isolates and four isolate pairs from separate sources in four
      separate patients, were typed using PCR amplification of repetitive extragenic
      palindromic sequences (REPS). The isolates identified as C. violaceum appeared to
      have identical REPS patterns, suggesting that some of the errant API results may
      be due to a single locally prevalent strain of B. pseudomallei. A previous
      suggestion that C. violaceum may produce a melioidosis-like illness may therefore
      be due to laboratory misidentification of B. pseudomallei with the API 20NE
      biochemical test panel.

PMID- 9534211
TI  - Actinomycosis of the cholecystic duct: case report and review.
AB  - Actinomycosis of the gall bladder, cholecystic duct or common bile duct is rare,
      with only 16 cases reported to our knowledge. We report a case of actinomycosis
      in the cholecystic duct remnant of an 80-year-old woman with a history of
      cholecystitis, choledocholithiasis and cholecystoduodenal fistula requiring
      cholecystectomy and fistula closure three years prior. Histologic sections of the
      cystic duct remnant showed several dense basophilic masses containing numerous,
      dark blue, Gram-positive branching bacilli compatible with actinomycotic
      granules. Fluorescent antibody staining was positive for Actinomyces naeslundii.
      Staining for acid-fast bacilli was negative. The pathogenesis, presentation,
      diagnosis and management of abdominal actinomycosis with specific reference to
      disease involving the gall bladder are discussed.

PMID- 9534212
TI  - Antibiotic resistance and genomic analysis of enterococci in an intensive care
      unit and general wards.
AB  - Fifty-nine enterococci isolated from 18 patients in an intensive care unit (ICU)
      and 21 patients in general wards (GW) at Royal Perth Hospital (RPH) during a
      period of 14 months were examined for antibiotic resistance by susceptibility
      testing and DNA polymorphism by pulsed-field gel electrophoresis. The study
      showed that penicillin-resistant Enterococcus faecium is a common nosocomial
      isolate in ICU. The DNA patterns of various strains of E. faecium and E. faecalis
      were closely related in most consecutive isolates from the same patients but were
      generally different for isolates from different patients. Thirty two different
      DNA patterns were identified for 59 isolates from 39 patients. Identical or
      similar DNA patterns were also identified for some isolates from different
      patients, suggesting that cross-infection had occurred between patients in ICU
      and GW. These data suggest that cross-infection occurred more commonly in ICU
      than in GW and are consistent with the known higher risk of ICU patients for
      nosocomial infection.

PMID- 9534213
TI  - New World cutaneous leishmaniasis imported into Australia.
AB  - A case of cutaneous leishmaniasis in a traveller from Belize, Central America is
      reported. Leishmaniasis presents rarely in Australia and delays in diagnosis and
      treatment often occur. A high index of suspicion in a patient who has returned
      from an endemic region is required. Subsequent confirmation of a diagnosis of
      cutaneous leishmaniasis is best achieved by demonstration of the organism on skin
      biopsy, aspiration or smear. The histology is variable and depends on geographic,
      parasite species and host factors. Speciation of New World disease as either
      Leishmania braziliensis or Leishmania mexicana is important to determine the risk
      of later development of mucosal disease, which normally only occurs with L.
      braziliensis infection, and for optimal treatment. Several different modes of
      treatment have been suggested, but antimonials, such as sodium stibogluconate,
      remain the treatment of choice in New World cutaneous leishmaniasis.

PMID- 9534215
TI  - Benign peripheral nerve sheath tumor of the seminal vesicle.

PMID- 9534214
TI  - Recurrent immature teratoma: lack of correlation between serum level and
      immunohistochemical detection of serum alpha-fetoprotein.
AB  - We present the clinicopathologic and immunohistochemical features of a pure
      immature ovarian teratoma that had arisen in a 15-year-old girl. At original
      diagnosis immature extra ovarian implants were noted (grade 3) accompanied by
      moderately elevated serum alpha-fetoprotein (AFP) levels. AFP was
      immunohistochemically demonstrable in immature endodermal elements. The immature
      neural tissue present was negative for AFP, and no other tumor elements were
      recognisable. Serum AFP fell post-operatively to within normal limits. Despite
      five courses of chemotherapy and asymptomatic status, the patient re-presented 15
      months after original diagnosis with a massive abdominal and pelvic tumor
      recurrence with predominantly mature glial tissue, but some persistent immature
      foci. There was no associated increase in serum AFP at this time. AFP was,
      however, persistently detectable immunohistochemically in immature endodermal
      components only. Immature neural elements were no longer identified.
      Disappearance of immature neural tissue in the tumor recurrence may have been
      related to chemotherapy. This case demonstrates the lack of correlative ability
      of serum AFP levels with both clinical behaviour and immunohistochemical
      demonstration of AFP expression in the tumor recurrence.

PMID- 9534216
TI  - The XIXth World Congress of Pathology and Laboratory Medicine. Versailles,
      France. 15-20 June, 1997.

PMID- 9534217
TI  - Synovial-like metaplasia around silicone breast implants.

PMID- 9534218
TI  - Family homelessness: state or trait?
AB  - Compares conceptualizations of homelessness as a temporary state through which
      people pass or a permanent trait that emanates from individual characteristics.
      Evidence from a longitudinal study of 564 homeless families in New York City and
      additional secondary sources supports the view that for families, homelessness is
      a temporary state that is resolved by the provision of subsidized housing. Even
      for single individuals with severe mental disturbances, housing is a key factor
      in ending homelessness, although here there is more evidence that social services
      also contribute. Policy implications are that governments should take a more
      active role in reducing homelessness by providing access to subsidized housing.

PMID- 9534219
TI  - Effect of favorable employment change on alcohol abuse: one- and five-year follow
      ups in the National Longitudinal Survey of Youth.
AB  - Job loss has been linked to adverse outcomes such as alcohol abuse, but improved
      employment, usually assumed to be beneficial, has seldom been evaluated and may
      not help with addictive disorders. Using the National Longitudinal Survey of
      Youth, young adults who were unemployed or underemployed (low income or
      involuntary part-time) in 1984 were followed up in 1985 and 1989. Controlling for
      1984 alcohol abuse, there were no effects of positive employment change on 1985
      symptoms, but there were significant restorative effects on 1985 binge drinking
      among those who were heavy drinkers in 1984. There also appeared to be an
      indirect link of favorable 1984-1985 employment change to heavy drinking in 1989
      via 1989 employment status. Because the effects of underemployment partially
      resembled those of unemployment, the discussion cautions against the conventional
      wisdom of promoting any work, including underemployment, as curative for the ills
      of unemployment.

PMID- 9534220
TI  - Volunteer participation in context: motivations and political efficacy within
      three AIDS organizations.
AB  - Employed quantitative and qualitative data in a contextual examination of
      participation in three San Francisco-area HIV/AIDS organizations: an urban, gay
      community-based social change setting; an urban, broadly focused
      information/referral setting; and a suburban individual support setting. The
      settings attracted different kinds of volunteers and engaged them differently
      with the setting, each other, and community. In quantitative analyses external
      political efficacy (belief in the responsiveness of sociopolitical systems to
      change efforts) significantly distinguished settings, but was best predicted by
      setting-moderated relationships to scaled motivations. Qualitative data more
      clearly illuminated volunteers' motivations for participation, as well as
      complex, embedded relationships between setting, motivations, attitudes about
      sociopolitical participation, and personal and community experience and
      identification. Together the findings underscore three unique but related stories
      for the three AIDS organizations, and the value of contextual approaches to
      participation and empowerment.

PMID- 9534221
TI  - Psychological dysfunction in Southeast Asian refugees as mediated by sense of
      coherence.
AB  - Investigated Antonovky's (1979, 1987) construct of sense of coherence (i.e., an
      individual's belief that the world was comprehensible, manageable, and
      meaningful) as the internal psychological mechanism mediating the effects of
      external stressors (generalized resistance deficits) and resources on
      psychological dysfunction (measured by depression, anxiety, and psychosocial
      dysfunction) in 2,234 Vietnamese, Cambodian, Laotian, Hmong, and Chinese
      Vietnamese refugees. Generalized resistance and deficits significantly predicted
      sense of coherence as well as psychological dysfunction. The amount of variance
      accounted for increased significantly when the mediating effect of sense of
      coherence was tested using a path analysis. Sense of coherence significantly
      reduced the predictive power of generalized resistance and deficits in the
      psychological dysfunction models. Results support the hypothesized mediating role
      of sense of coherence. Thus, interventions aiming to enhance Southeast Asian
      refugees' functioning may gain in effectiveness by targeting and promoting their
      sense of coherence.

PMID- 9534222
TI  - Effects of different telephone intervention styles with suicidal callers at two
      suicide prevention centers: an empirical investigation.
AB  - To determine the relative effectiveness of telephone intervention styles with
      suicidal callers, researchers listened unobtrusively to 617 calls by suicidal
      persons at two suicide prevention centers and categorized all 66,953 responses by
      the 110 volunteer helpers according to a reliable 20-category checklist. Outcome
      measures showed observer evaluations of decreased depressive mood from the
      beginning to the end in 14% of calls, decreased suicidal urgency ratings from the
      beginning to the end in 27% of calls, and reaching a contract in 68% of calls, of
      which 54% of contracts were upheld according to follow-up data. Within the
      context of relatively directive interventions, a greater proportion of "Rogerian"
      nondirective responses was related to significantly more decreases in depression.
      Reduction in urgency and reaching a contract were related to greater use of
      Rogerian response categories only with nonchronic callers.

PMID- 9534223
TI  - Validity of adolescents' report of maternal age.
AB  - Examined the validity of adolescents' reports of their mother's age. Most
      research on the validity of self-report focuses on personal behaviors such as
      alcohol and substance use, or response bias due to social desirability. Few
      studies investigate the validity of adolescents reporting of nonsensitive
      information. Data from 80 mother-adolescent pairs were collected. The sample
      included 9th graders from four high school English classes, equal numbers of
      males and females, and 15% African Americans. The correlation between mothers'
      reports and youths' reports of mother's age was .99, and 95% of the youth were
      within a year of their mother's correct age. No race or gender differences were
      found. These results allow researchers to examine adolescent outcomes for youth
      born to teen mothers without the expense of also collecting data from their
      mothers. Results also suggest that adolescents' self-reports of other
      nonsensitive familial data may also be valid.

PMID- 9534224
TI  - Further examples of orthoesterification under kinetically controlled conditions.
      Application to the selective acylation of sucrose, maltose and alpha,alpha
      trehalose.
AB  - Orthoesterification of sucrose with 1,1-dimethoxyethene under kinetic control
      gave 4,6-O-methoxyethylidenesucrose in 77% crude yield. Similar
      orthoesterification of maltose led essentially after acetylation to 1,2,3,6,2',3'
      hexa-O-acetyl-4'-6'-O-methoxyethylidenemaltose. Analogous treatment of alpha,
      alpha-trehalose gave 2,3,2',3'-tetra-O-acetyl-4,6:4',6'-di-O-methoxyethylidene
      alpha, alpha-trehalose in 47% yield. The acid-catalyzed opening of these
      orthoesters was studied, and these reactions were shown to give disaccharides
      selectively protected by acetyl groups.

PMID- 9534225
TI  - Synthesis of 1,2,3-tri-O-beta-lactosyl-D-threitol and 1-O-benzyl-2,3,4-tri-O-beta
      lactosyl-D-threitol.
AB  - The coupling of 2,3,6,2',3',4',6-hepta-O-acetyl-alpha-lactosyl bromide with 1,4
      di-O-benzyl-D-threitol using mercury(II) cyanide as a promoter, with subsequent
      deprotection of one or both of the benzyl groups, further glycosylation, and
      deacetylation afforded the title compounds. This class of compound is useful in
      the assessment of binding properties of D-galactopyranose to human and rabbit
      hepatocytes.

PMID- 9534226
TI  - Synthetic approach towards sulfated chondroitin di-, tri- and tetrasaccharides
      corresponding to the repeating unit.
AB  - Chondroitin di-, tri- and tetrasaccharides, as well as their 4-, 6-mono- and 4,6
      disulfates as their 4-methoxyphenyl glycosides, were systematically synthesized.
      Target disaccharides having beta GalNAc-(1-->4)-beta GlcA sequences were obtained
      starting from the corresponding pivotal chondroitin disaccharide precursor. A
      trisaccharide intermediate, which was synthesized by coupling of glucuronate
      imidate with a known disaccharide acceptor, was transformed into the sulfated and
      non-sulfated chondroitin trisaccharides. Chondroitin tetrasaccharide and the
      corresponding 4-disulfate, 6-disulfate as well as 4,6-tetrasulfate were also
      obtained based on the strategy developed above starting from the reported
      tetrasaccharide having [beta GalN3-(1-->4)-beta GlcA2] sequence.

PMID- 9534227
TI  - Structure of the capsular polysaccharide of Clostridium perfringens Hobbs 10
      determined by NMR spectroscopy.
AB  - The complete primary structure of the type-specific capsular polysaccharide of
      Clostridium perfringens Hobbs 10 was determined. The polysaccharide was isolated
      from C. perfringens Hobbs 10 by cold-water extraction of whole, heavily
      encapsulated cells. The polysaccharide was purified, by ethanol precipitation,
      deproteination, selective precipitation with hexadecyltrimethylammonium bromide,
      ion-exchange chromatography and gel-filtration chromatography. The polysaccharide
      was comprised of D-glucose, D-galactose, N-acetylgalactosamine, and iduronic
      acid, in molar ratios of 2:2:1:1. Sequence and linkage assignments of the
      glycosyl residues were obtained by NMR spectroscopy, specifically by the
      combination of two-dimensional homonuclear DQF-COSY, TQF-COSY and TOCSY,
      heteronuclear ?1H, 13C? single-quantum coherence (HSQC) and heteronuclear
      multiple-bond correlation (HMBC) experiments. The capsular polysaccharide of C.
      perfringens Hobbs 10 is a polymer composed of a hexasaccharide repeating unit
      with the following structure: [formula: see text] This structure is novel among
      bacterial cell-surface polysaccharides, and it is only the second of many
      serotypically distinct capsular polysaccharides of C. perfringens to be
      described.

PMID- 9534228
TI  - Transglycosylation activity of alpha-D-galactosidase from Trichoderma reesei. An
      investigation of the active site.
AB  - The transglycosylation reaction catalyzed by alpha-D-galactosidase from the
      mycelial fungus Trichoderma reesei was studied using p-nitrophenyl alpha-D
      galactopyranoside (PNPG). An aliphatic alcohol or the substrate itself can be an
      acceptor of the galactose residue in this reaction. The transglycosylation
      products were identified as alkyl galactosides in the case of alcohols or as
      galactobioside and galactotrioside in the case of PNPG. The transglycosylation
      rates follow a first-order equation with respect to the alcohol concentrations
      except for methanol. Affinities of some substrates were estimated from their Ki
      values in the reaction of the enzyme with PNPG. Transglycosylation of the
      substrate suggests a model for the enzyme active center. It is proposed that the
      active center includes two galactose-binding sites and a hydrophobic site.

PMID- 9534229
TI  - Conformational stabilization of the altruronic acid residue in the O-specific
      polysaccharide of Shigella sonnei/Plesiomonas shigelloides.
AB  - Complete assignments for the 1H- and the 13C-NMR spectra of the O-specific
      polysaccharide of S. sonnei/Plesiomonas shigelloides are reported. Evidence is
      presented that in this polysaccharide both pyranose residues exist preferentially
      in the 4C1 chair conformation and that the polysaccharide exists in the
      zwitterion form.

PMID- 9534230
TI  - Effect of deacetylation on the synergistic interaction of acetan with locust bean
      gum or konjac mannan.
AB  - It has been discovered that deacetylation of the bacterial polysaccharide acetan
      promotes synergistic interactions with either locust bean gum (LBG) or konjac
      mannan (KM). Acetan is similar in structure to xanthan, and adopts a similar 5
      fold conformation in the solid state. Like xanthan, it shows a thermally
      reversible order (helix)-disorder (coil) transition in solution. Both polymers
      have a cellulosic backbone with charged (anionic) sidechains attached at O-3 of
      alternate glucosyl residues, but the sidechains in acetan are longer
      (pentasaccharide rather than trisaccharide) and do not contain pyruvic
      substituents. Acetan has two sites of acetylation, one at O-6 of the inner
      mannosyl residue of the carbohydrate sidechains (as in xanthan) and the other on
      the polymer backbone (believed to be at O-6 of the branched glucosyl residues).
      Solutions of acetan or deacetylated acetan were equilibrated against 10 mM
      potassium chloride (to stabilise the ordered conformation) and were mixed (at 25
      degrees C) with solutions of LBG or KM, also equilibrated against 10 mM potassium
      chloride. Unlike xanthan, native acetan showed no evidence of synergistic
      interaction with either LBG or KM. After deacetylation, however, large
      enhancements were observed in dilute-solution viscosity, and thermoreversible
      gels were formed at higher concentrations. With KM as co-synergist, gel melting
      was accompanied by an intense endotherm in differential scanning calorimetry. The
      magnitude of this endotherm increased with storage time at 25 degrees C, reaching
      a final value of delta H approximately 15.9 J/g (in comparison with delta H
      approximately 5.0 J/g for the order-disorder transition of deacetylated acetan
      alone). It is suggested that interaction occurs by formation of heterotypic
      junctions between the acetan backbone and unsubstituted regions of the plant
      polysaccharide, and that the acetate groups on native acetan promote solubility
      and hence inhibit association.

PMID- 9534231
TI  - The production of a new water-soluble polysaccharide by Acetobacter xylinum NCI
      1005 and its structural analysis by NMR spectroscopy.
AB  - A new water-soluble polysaccharide (WSP) was isolated from a culture of
      Acetobacter xylinum NCI 1005 grown on sucrose. The structure of the WSP was
      analysed by nuclear magnetic resonance spectroscopy and determined to be a beta
      (2-->6)-linked polyfructan, which is structurally different from the polymer
      synthesized from glucose instead of sucrose by the same strain. The discovery of
      this new polysaccharide has revealed that the bacterium is able to synthesize two
      different kinds of water-soluble polysaccharides.

PMID- 9534232
TI  - Horizontal spread of mer operons among gram-positive bacteria in natural
      environments.
AB  - Horizontal dissemination of the genes responsible for resistance to toxic
      pollutants may play a key role in the adaptation of bacterial populations to
      environmental contaminants. However, the frequency and extent of gene
      dissemination in natural environments is not known. A natural horizontal spread
      of two distinct mercury resistance (mer) operon variants, which occurred amongst
      diverse Bacillus and related species over wide geographical areas, is reported.
      One mer variant encodes a mercuric reductase with a single N-terminal domain,
      whilst the other encodes a reductase with a duplicated N-terminal domain. The
      strains containing the former mer operon types are sensitive to organomercurials,
      and are most common in the terrestrial mercury-resistant Bacillus populations
      studied in this work. The strains containing the latter operon types are
      resistant to organomercurials, and dominate in a Minamata Bay mercury-resistant
      Bacillus population, previously described in the literature. At least three
      distinct transposons (related to a class II vancomycin-resistance transposon,
      Tn1546, from a clinical Enterococcus strain) and conjugative plasmids are
      implicated as mediators of the spread of these mer operons.

PMID- 9534233
TI  - Loss-of-function mutations in the mtr efflux system of Neisseria gonorrhoeae.
AB  - Resistance of Neisseria gonorrhoeae to antimicrobial hydrophobic agents (HAs) has
      been ascribed to the mtr (multiple transferable resistance) operon. This operon
      is composed of the mtrR gene, which encodes a transcriptional repressor (MtrR),
      and a three-gene complex (mtrCDE), which encodes cell envelope proteins (MtrC
      MtrD-MtrE) that form an energy-dependent efflux pump. HA-hypersusceptible strains
      are often isolated from patients, but the genetic basis for such
      hypersusceptibility was heretofore unknown. The genetic basis of HA
      hypersusceptibility in laboratory-derived strains BR54 and BR87 was studied to
      learn if this trait could be linked to mutations in the mtr operon. Mutations in
      the mtrR gene of these strains that could be phenotypically suppressed by
      mutations in their mtrC or mtrD genes were identified. Thus, small deletions (4
      10 bp) in the mtrC or mtrD genes of strains BR87 and BR54 that would result in
      the production of truncated efflux pump proteins that serve as a membrane fusion
      protein (MtrC) or transporter of HAs (MtrD) were found to be responsible for
      their HA-hypersusceptible property.

PMID- 9534235
TI  - Re-evaluation of the serotypes of Serratia marcescens and separation into two
      schemes based on lipopolysaccharide (O) and capsular polysaccharide (K) antigens.
AB  - Chemical and serological analysis has revealed that many of the 29 O serotype
      reference strains of Serratia marcescens contain both neutral and acidic
      polysaccharides which correspond to LPS O antigens and capsular K antigens,
      respectively. New O and K antigen typing schemes have therefore been devised,
      based on the known chemical structures of the surface polysaccharides of the
      organism. These schemes were designed to allow the specific detection of these
      antigens on unknown strains using ELISAs. O antigens were detected using whole
      cells cultured in broth then autoclaved to remove capsular material, while K
      antigens were detected using formolized whole cells which had been cultured on
      glycerol agar to enhance capsule production. After testing with the 29 reference
      strains as well as 423 distinct clinical strains, it was apparent that different
      aspects of chemical structure were associated with different degrees of
      serological reactivity and the typing schemes were modified further to
      accommodate this. In general, the O antigen repeating unit structures were
      chemically simple with di- or trisaccharide backbones. Serological specificity
      was often provided solely by the presence or absence of an O-acetyl substituent,
      or a change in the linkage between two sugar residues. Five of the O serotypes in
      the new scheme were represented by 12 of the 29 reference strains, while three
      reference strains lacked O antigens altogether, resulting in the elimination of
      10 of the original O types. In contrast, the K antigen repeating unit structures
      were more complex and chemically diverse, having at least four sugar residues.
      Three K types were each seen in two reference strains while 12 of the 29
      reference strains were acapsular. Thus, the resulting schemes contain 19 O types
      and 14 K types and allow the definitive serotype identification of S. marcescens.

PMID- 9534234
TI  - Extensive genetic diversity among clinical isolates of Streptococcus pyogenes
      serotype M5.
AB  - The genetic diversity of clinical isolates of Streptococcus pyogenes serotype M5
      has been characterized. Strain genotypes were defined by macrorestriction
      profile, 16S ribotype, emm gene subtype, insertion element IS1239 profile, and
      exotoxin gene determinant. By these criteria, clinical isolates of M5 constituted
      a multiplicity of strain clusters rather than a homogeneous population as found
      for certain serotypes. Distance matrices and an unrooted tree were constructed
      from macrorestriction data with three rarely cutting endonucleases, determined by
      PFGE. A single IS1239 profile was common to 85% of isolates but there was great
      diversity of both ribotype and macrorestriction profile, and 18 different emm
      gene subtypes were detected by PCR-RFLP. DNA sequence analysis of the antigen
      coding 5' (hypervariable) region of emm gene amplicons (about 240 bp) showed that
      14/18 exhibited up to 6% divergence. Four amplicons had highly divergent
      sequences--corresponding to those previously determined for emm6, emm11, emm18
      and emm77. Further serological and hybridization studies were used to analyse the
      discrepancy between the Lancefield serotype of these strains (M5) and their emm
      genotype. Overall, this study shows a high degree of genetic diversity in
      serotype M5, with implications for the Lancefield scheme itself, for the
      epidemiology of group A streptococci, and for recombinant DNA strategies for M
      protein-based vaccine development.

PMID- 9534236
TI  - Magnesium transport in Salmonella typhimurium: biphasic magnesium and time
      dependence of the transcription of the mgtA and mgtCB loci.
AB  - Salmonella typhimurium has three distinct Mg2+ transport systems, the
      constitutive high-capacity CorA transporter and two P-type ATPases, MgtA and
      MgtB, whose transcription is repressed by normal concentrations of Mg2+ in the
      growth medium. The latter Mg(2+)-transporting ATPase is part of a two-gene
      operon, mgtCB, with mgtC encoding a 23 kDa protein of unknown function.
      Transcriptional regulation using fusions of the promoter regions of mgtA and
      mgtCB to luxAB showed a biphasic time and Mg2+ concentration dependence. Between
      1 and 6 h after transfer to nitrogen minimal medium containing defined
      concentrations of Mg2+, transcription increased about 200-fold for mgtCB and up
      to 400-fold for mgtA, each with a half-maximal dependence on Mg2+ of 0.5 mM.
      Continued incubation revealed a second phase of increased transcription, up to
      2000-fold for mgtCB and up to 10,000-fold for mgtA. This secondary increase
      occurred between 6 and 9 h after transfer to defined medium for mgtCB but between
      12 and 24 h for mgtA and had a distinct half-maximal dependence for Mg2+ of 0.01
      mM. A concomitant increase of at least 1000-fold in uptake of cation was seen
      between 8 and 24 h incubation with either system, showing that the
      transcriptional increase was followed by functional incorporation of large
      amounts of the newly synthesized transporter into the membrane. Regulation of
      transcription by Mg2+ was not dependent on a functional stationary-phase sigma
      factor encoded by rpoS, but it was dependent on the presence of a functional
      phoPQ two-component regulatory system. Whereas mgtCB was completely dependent on
      regulation via phoPQ, the secondary late Mg(2+)-dependent phase of mgtA
      transcription was still evident in strains carrying a mutation in either phoP or
      phoQ, albeit substantially diminished. Several divalent cations blocked the early
      phase of the increase in transcription elicited by the decrease in Mg2+
      concentration, including cations that inhibit Mg2+ uptake (Co2+, Ni2+ and Mn2+)
      and those which do not (Ca2+ and Zn2+). In contrast, the second later phase of
      the transcriptional increase was not well blocked by any cation except those
      which inhibit uptake. Overall, the data suggest that at least two distinct
      mechanisms for transcriptional regulation of the mgtA and mgtCB loci exist.

PMID- 9534237
TI  - Role of trehalose in survival of Saccharomyces cerevisiae under osmotic stress.
AB  - Trehalose is an enigmatic compound that accumulates in Saccharomyces cerevisiae
      and has been implicated in survival under various stress conditions by acting as
      membrane protectant, as a supplementary compatible solute or as a reserve
      carbohydrate that may be mobilized during stress. In this study, specific mutants
      in trehalose metabolism were used to evaluate whether trehalose contributes to
      survival under severe osmotic stress and generates the compatible solute glycerol
      under moderate osmotic stress. The survival under severe osmotic stress (0.866
      aw' NaCl or sorbitol) of mutants was compared to that of the wild-type strain
      when cultivated to either the mid-exponential or the stationary growth phase on
      glucose, galactose or ethanol. Stationary-phase cells survived better than
      exponential-phase cells. The death rates of ethanol-grown cells were lower than
      those of galactose-grown cells, which in turn survived better than glucose-grown
      cells. There was a strong relationship between intracellular trehalose levels and
      resistance to osmotic stress. The mutant strains unable to produce trehalose
      (tps1 delta tps2 delta and tps1 delta hxk2 delta) were more sensitive to severe
      osmotic stress (0.866 aw) than the isogenic wild-type strain, confirming a role
      for trehalose in survival. Hyperaccumulation of trehalose found in the nth1 delta
      and the nth1 delta gpd1 delta mutant strains, however, did not improve survival
      rates compared to the wild-type strain. When wild-type, nth1 delta and nth1 delta
      gpd1 delta cells were exposed to moderate osmotic stress (0.98 and 0.97 aw'
      NaCl), which permits growth, glycerol production did not appear to be related to
      the intracellular trehalose levels although glycerol levels increased more
      rapidly in nth1 delta cells than in wild-type cells during the initial response
      to osmotic stress. These data indicate that trehalose does not act as a reserve
      compound for glycerol synthesis under these conditions. No evidence was found for
      solutes other than glycerol and trehalose being significant for the survival of
      or growth by S. cerevisiae under osmotic stress conditions.

PMID- 9534238
TI  - Thigmotropism and stretch-activated channels in the pathogenic fungus Candida
      albicans.
AB  - The direction of growth of hyphae of the pathogenic fungus Candida albicans
      responds thigmotropically to surface contours by following scratches, ridges and
      grooves and by penetrating pores. Here it is shown that the thigmotropic response
      to ridges is attenuated by GdCl3 and verapamil [blockers of stretch-activated
      (SA) ion channels and L-type calcium channels, respectively]. At low
      concentrations, both compounds reduced the percentage of hyphae reorienting on
      contact with a ridge without markedly affecting hyphal extension rate, suggesting
      a possible role for SA or other calcium channels in the transduction of the
      thigmotropic response. In addition, patch-clamp recordings demonstrated SA
      channel activity in the plasma membrane of both yeast and hyphal cells of C.
      albicans. Two distinct SA channels with conductances of 54 pS and 20-25 pS in 200
      mM KCl were observed in protoplasts from yeast cells and one channel of 51 pS was
      found in protoplasts from hyphal cells.

PMID- 9534239
TI  - Expression of the cold-shock gene cspB in Salmonella typhimurium occurs below a
      threshold temperature.
AB  - Previous studies have shown that several bacterial species exhibit a multigenic
      response following temperature downshift (cold shock). Evidence for such a
      response in Salmonella typhimurium is reported, based on the isolation of a range
      of low-induction-temperature gene fusions containing Mudlux insertions. The
      fusions exhibited different levels of basal light at 30 degrees C, and were
      induced at different rates and to different degrees over several hours following
      a reduction in temperature to 10 degrees C. Of the Mudlux gene fusions isolated,
      one was found which produced essentially no light when grown at 30 degrees C but
      exhibited rapid and high-level induction when the temperature was reduced to 10
      degrees C. The target of this gene fusion (which was named cspB) was shown to lie
      adjacent to the umuDC operon and to encode a homologue of the major cold-shock
      protein of Escherichia coli, CspA. Luminescence studies revealed that substantial
      light production occurred from the cspB::Mudlux fusion at or below 22 degrees C
      but not at higher temperatures, even following a temperature drop from 30 degrees
      C. Moreover, cspB mRNA levels were found to mimic this pattern of luminescence,
      suggesting that cspB expression occurs below a defined temperature threshold. The
      cspB mRNA was also found to be very stable at 10 degrees C but to become highly
      unstable when the temperature was raised towards the threshold temperature, even
      in the presence of rifampicin. Existing cellular RNases therefore appear to
      mediate the decay of cspB mRNA at high temperatures, but are incapable of this at
      low temperatures.

PMID- 9534240
TI  - A novel regulatory switch mediated by the FNR-like protein of Lactobacillus
      casei.
AB  - FNR (regulator for fumarate and nitrate reduction) and CRP (cAMP receptor
      protein) are global regulators which regulate the transcription of overlapping
      modulons of target genes in response to anaerobiosis and carbon source in
      Escherichia coli. An ORF, designated flp because it encodes an FNR-like protein
      of the FNR-CRP family, has been found in Lactobacillus casei. The product of the
      flp coding region (FLP) was overproduced in E. coli, purified and crystallized.
      FLP is a homodimeric protein in which each subunit can form an intramolecular
      disulphide bond. The isolated protein also contains non-stoichiometric amounts of
      Cu and Zn. Although the DNA recognition helix of FLP resembles that of FNR, the
      flp gene failed to complement the anaerobic respiratory deficiency of an fnr
      mutant when expressed in E. coli and it neither activated nor interfered with
      transcription from FNR- or CRP-dependent promoters in E. coli. Site-specific DNA
      binding by oxidized FLP (the form containing intrasubunit disulphide bonds) was
      abolished by reduction. The interconversion between disulphide and dithiol forms
      thus provides the basis for a novel redox-mediated transcriptional switch. Two
      non-identical FLP-binding sites, distinct from FNR- and CRP-binding sites, were
      identified in the meIR region of E. coli by gel-retardation analysis. A further
      eight FLP-binding sites were selected from a random library. A synthetic
      oligonucleotide conforming to a putative FLP site consensus, CA/CTGA-N4-TCAG/TG
      (the most significant bases are underlined), was retarded by FLP. Functional
      tests showed that FLP represses the aerobic transcription of a semi-synthetic
      promoter in E. coli. A C5S variant of FLP lacking the ability to form
      intramolecular disulphide bonds was unable to bind to FLP sites and failed to
      repress transcription in vivo.

PMID- 9534241
TI  - The S-layer gene of Lactobacillus helveticus CNRZ 892: cloning, sequence and
      heterologous expression.
AB  - Lactobacillus helveticus CNRZ 892 contains a surface layer (S-layer) composed of
      protein monomers of 43 kDa organized in regular arrays. The gene encoding this
      protein (slpH) has been cloned in Escherichia coli and sequenced. slpH consists
      of 440 codons and is preceded by a ribosome-binding site (RBS) and followed by a
      putative rho-independent terminator. Indeed, Northern analysis revealed that slpH
      is a monocistronic gene. The gene is preceded by a possible promotor of which the
      -35 and -10 hexanucleotides are separated by 17 nt. By primer extension analysis
      the transcription start site was mapped at 7 nt downstream of the -10 sequence
      while the deduced amino acid sequence of SlpH shows a leader peptide of 30 aa.
      The slpH gene has been amplified by PCR and the fragment, carrying the complete
      gene from the RBS to the stop codon, has been cloned in a lactococcal gene
      expression vector downstream of promoter P32. Lactococcus lactis MG1363 carrying
      the resulting plasmid produced and secreted an S-layer monomer with the same
      molecular mass as the authentic L. helveticus CNRZ 892 SlpH, as judged by SDS
      PAGE. Immunoelectron microscopy revealed that SlpH was bound to the lactococcal
      cell walls in small clumps and accumulated in the growth medium as small sheets.

PMID- 9534242
TI  - A response-regulator-like activator of antibiotic synthesis from Streptomyces
      coelicolor A3(2) with an amino-terminal domain that lacks a phosphorylation
      pocket.
AB  - In Streptomyces coelicolor A3(2), bldA mutants that lack the tRNA for the rare
      leucine codon UUA fail to make the red undecylprodigiosin antibiotic complex. To
      find out why, red-pigmented while bald (Pwb) derivatives of a bldA mutant were
      isolated. Using a cloning strategy that allowed for (and demonstrated) dominance
      of the mutations, they were localized to the red gene cluster. By using insert
      mediated integration of a phi C31 phage-based vector, one of the Pwb mutations
      was more precisely located between red structural genes to a segment of
      approximately 1 kb about 4 kb from the known pathway-specific regulatory gene
      redD. The segment contained most of an ORF (redZ) encoding a protein (RedZ) with
      end-to-end similarity to response regulators of diverse function from a variety
      of bacteria. Remarkably, in RedZ hydrophobic residues replace nearly all of the
      charged residues that usually make up the phosphorylation pocket present in
      typical response regulators, including the aspartic acid residue that is normally
      phosphorylated by a cognate sensory protein kinase. A single TTA codon in redZ
      provided a potential explanation for the bldA-dependence of undecylprodigiosin
      synthesis. This codon was unchanged in three Pwb mutants, but further analysis of
      one of the mutants revealed a potential up-promoter mutation. It seems possible
      that a combination of low-level natural translation of the UUA codon by a charged
      non-cognate tRNA, coupled with increased transcription of redZ in the Pwb mutant
      allows the accumulation of a threshold level of the RedD protein.

PMID- 9534243
TI  - Stationary phase, amino acid limitation and recovery from stationary phase
      modulate the stability and translation of chloramphenicol acetyltransferase mRNA
      and total mRNA in Escherichia coli.
AB  - The functional stability of the chloramphenicol acetyltransferase (cat) mRNA, as
      well as the functional stability of the total mRNA pool, change during the course
      of Escherichia coli culture growth. mRNA half-lives are long during lag phase,
      decrease during the exponential phase and increase again during the stationary
      phase of the bacterial growth cycle. The half-lives of cat mRNA and total mRNA
      also increase three- to fourfold during amino acid starvation when compared to
      exponential culture growth. Even though the stability of the cat message changes
      about fourfold during culture growth, the amount of cat mRNA per cell mass does
      not vary significantly between the culture growth phases, indicating that there
      are compensating changes in cat gene transcription. Translation of cat mRNA also
      changes during culture growth. In exponential phase, the rate of cat translation
      is about 14-fold higher than when the culture is in stationary phase. This is in
      contrast to the fourfold increase in stability of cat mRNA in the stationary
      phase culture compared to the exponentially growing culture and indicates that
      active translation is not correlated with increased mRNA stability. When a
      stationary-phase culture was diluted into fresh medium, there was a five- to
      sevenfold increase in CAT synthesis and a threefold increase in total protein
      synthesis in the presence or absence of rifampicin. These results suggest that
      while mRNA becomes generally more stable and less translated in the stationary
      phase culture, the mRNA is available for immediate translation when nutrients are
      provided to the culture even when transcription is inhibited.

PMID- 9534244
TI  - Expression of the second lysine decarboxylase gene of Escherichia coli.
AB  - Certain amino acids are substrates for two decarboxylase enzymes in Escherichia
      coli, one inducible by anaerobic growth at low pH and the other constitutive. In
      the case of lysine, an inducible decarboxylase (CadA) has been extensively
      characterized, but evidence for the existence of a second lysine decarboxylase is
      fragmentary and uncertain. This paper confirms that a second lysine decarboxylase
      is encoded by a locus (ldc) previously suggested to be a lysine decarboxylase
      gene on the basis of sequence comparisons. Overexpression of the cloned gene
      provided sufficient quantities of enzyme in cell-free extracts for preliminary
      examination of the properties of the ldc gene product, Ldc. The enzyme is active
      over a broad range of pH with an optimum at 7.6, much higher than that of CadA,
      about 5.5. The temperature optimum for both enzymes is similar, at about 52
      degrees C, but Ldc is more readily inactivated by heat than CadA. Expression of
      ldc from its own promoter was very weak for cells growing in a variety of media,
      although a low level of lysine decarboxylase was present in cells that carried
      the ldc region on an oligo-copy plasmid when these were grown in minimal-glucose
      medium. Northern analysis of RNA extracted from such cells revealed a transcript
      whose length corresponded to that of the ldc gene, suggesting that ldc is
      normally transcribed from a promoter immediately upstream. However, most of the
      ldc mRNA was shorter, indicating degradation or premature termination. The ldc
      upstream sequence promoted transcription of a lacZ gene to which it was fused.
      Introduction of the upstream sequence as an insert in a multicopy vector
      increased transcription of the resident lacZ fusion. The low level of expression
      in single copy, the emergence of expression when the gene is present at moderate
      copy number, and the derepression by the upstream sequence in trans imply that
      this second lysine decarboxylase gene may not be constitutive but subject to
      specific repression by a factor which remains to be identified.

PMID- 9534245
TI  - Mycoplasma hominis expresses two variants of a cell-surface protein, one a
      lipoprotein, and one not.
AB  - A protein similar to the previously characterized variable surface-exposed
      membrane protein P120 was identified (P120'), establishing that Mycoplasma
      hominis PG21 possesses a novel gene family. The gene, p120', was sequenced and
      found to have some distinctive properties including a putative start codon of
      GTG, rather than the common ATG codon, and a coding region with a high G + C
      content, characteristic of essential housekeeping genes in mycoplasmas. No
      sequence homology was found to known proteins. The genomic locations of the p120
      and p120' genes were determined on the restriction map of five M. hominis strains
      by PFGE. The genes were localized in two separate regions separated by more than
      6 kb. Genes as well as proteins corresponding to P120' were identified in 24/24
      M. hominis isolates tested and no size variation was detected. P120' had a
      molecular mass of 98 kDa, 20 kDa smaller than P120 as estimated by SDS-PAGE. The
      protein was surface-exposed and associated with the mycoplasma membrane, but had
      predominantly hydrophilic characteristics upon Triton X-114 extraction. The N
      terminal part of P120' had a hydrophobic leader sequence without the
      characteristics of a prolipoprotein. This might explain the membrane association
      of the protein. Unlike P120, which is frequently recognized by sera of patients
      seropositive for M. hominis, P120' was only rarely recognized. The conserved
      nature of the P120 gene family indicates that it has an essential, although
      currently unknown, function.

PMID- 9534247
TI  - Fast purification of thioredoxin reductases and of thioredoxins with an unusual
      redox-active centre from anaerobic, amino-acid-utilizing bacteria.
AB  - Thioredoxin reductase and thioredoxin are primarily involved in catabolic
      metabolism as important electron carriers in anaerobic, amino-acid-degrading
      bacteria. A general and fast procedure was developed for the purification of
      thioredoxin reductase and thioredoxin from Eubacterium acidaminophilum,
      Clostridium litorale, C. sticklandii, C. sporogenes, C. cylindrosporum and
      'Tissierella creatinophila' based upon their properties: the binding to 2',5'-AMP
      Sepharose by thioredoxin reductase and the inability of thioredoxins to bind to a
      DEAE-Sephacel column. The consensus sequence at the active site of thioredoxins (
      WCGPC-) was found to be modified in all of these anaerobes: Trp-31 (Escherichia
      coli nomenclature) was replaced by Gly or Ser, Gly-33 by Val or Glu. None of
      these thioredoxins reacted with thioredoxin reductase of E. coli or vice versa,
      but they did interact with the thioredoxin reductases obtained from the other
      anaerobes studied. Based upon their distinguishing features it is suggested that
      these thioredoxins might form an evolutionarily separate group.

PMID- 9534248
TI  - A 28 kbp segment from the spoVM region of the Bacillus subtilis 168 genome.
AB  - The sequence of a 28 kbp segment of DNA surrounding the spoVM gene of Bacillus
      subtilis 168 (lying at approximately 145 degrees on the standard genetic map) has
      been determined. The region contains 27 ORFs, a number of which have predicted
      products significantly similar to proteins in sequence databases, particularly to
      proteins involved in macromolecular synthesis of nucleic acids, proteins and
      phospholipids. A pair of closely linked genes encode a likely serine protein
      phosphatase and a serine protein kinase, respectively. Such proteins play
      important regulatory roles in eukaryotic cells but are rare in prokaryotes.

PMID- 9534249
TI  - Determination of a 15437 bp nucleotide sequence around the inhA gene of
      Mycobacterium avium and similarity analysis of the products of putative ORFs.
AB  - A 15437 bp region encompassing the inhA locus from the Mycobacterium avium
      chromosome was cloned and sequenced. From the sequencing data generated and the
      results of homology searches, the primary structure of this region was
      determined. This region contains four known genes (acnA, fabG, inhA and hemH) and
      two genes, invA and invB, whose products display homology with p60 invasion
      protein of Listeria monocytogenes. Six proteins encoded by putative ORFs
      contained an RGD motif (often involved in binding to macrophage integrins), while
      ORF1 and MoxR are probably transcriptional regulators. The rest of the putative
      products encoded by ORFs in the sequenced region showed little homology with the
      proteins contained in the databases and were considered to be unknown proteins.

PMID- 9534250
TI  - beta-Carboline alkaloids as matrices for UV-matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry in positive and negative
      ion modes. Analysis of proteins of high molecular mass, and of cyclic and acyclic
      oligosaccharides.
AB  - We report that commercially available beta-carbolines (nor-harmane (9H-pyrido[3,4
      b]indole), harmane (1-methyl-9H-pyrido[3,4-b]indole), harmine (7-methoxy-1-methyl
      9H-pyrido[3,4-b]indole), harmol (1-methyl-9H-pyrido[3,4-b]indol-7-ol), harmaline
      (3,4-dihydro-7-methoxy-1-methyl-9H-pyrido[3,4-b]indole) and harmalol (3,4-dihydro
      1-methyl-9H-pyrido[3,4-b]indol-7-ol)), are useful MALDI matrices at 337 nm, for
      cyclic oligosaccharides (cyclodextrins, range 972-1290 Da), acyclic
      oligosaccharides (range 342-828 Da) and high molecular mass proteins (range
      23,290-66,525 Da) in both positive and negative modes. This was investigated by
      using time-of-flight (TOF) mass spectrometers of different sensitivities,
      equipped with and without pulse extraction facilities. A comparison with
      conventional matrices for carbohydrates (DHB and DHB/HIC) indicates that beta
      carbolines provide the same level of sensitivity and resolution in the positive
      mode, but offer the advantage of high levels of sensitivity and resolution in the
      negative mode. Harmaline has been found to be specially effective for the
      analysis of high-mass proteins in both modes, and also exhibits excellent
      experimental reproducibility of the results owing to the homogeneous
      crystallization of the analyte-matrix mixture over the entire sample surface
      area. Harmane and nor-harmane are both excellent matrices for high-mass proteins
      also. As MALDI matrices, beta-carbolines permit measurement of sulfated sugars in
      the negative ion mode as ([M-H]), and of neutral sugars and proteins as both [M +
      H]+ and [M-H]- in appropriate modes.

PMID- 9534251
TI  - Influence of different glycosidic linkages on relative ion intensities in post
      source decay fragmentation of a xyloglucan heptaoligosaccharide using matrix
      assisted laser desorption/ionization time-of-flight mass spectrometry.
AB  - Post-source decay fragment analysis using matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) has been
      applied to a highly branched xyloglucan heptasaccharide from tamarind seed. All
      fragment ions were produced by cleavage of the glycosidic linkages, including
      multi-site cleavages. The relative intensities of fragment ions that originated
      from one-site cleavages of the glycosidic linkages were much higher than those
      arising from two-site cleavages of the same kind of glycosidic linkage, which
      were in turn higher than those from three-site cleavages. The types of glycosidic
      linkages were an important factor which influenced the relative intensities of
      the MALDI-PSD (post-source decay) fragment ions. In the MALDI-PSD fragment
      spectrum of the xyloglucan heptasaccharide, the relative intensities of the ions
      produced by the cleavage of an alpha 1-6 glycosidic linkage were much higher than
      those arising from cleavage of the beta 1-4 glycosidic linkage.

PMID- 9534252
TI  - Quantitative analysis of antibiotics by matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry.
AB  - Comparative studies of the matrix-assisted laser desorption/ionization (MALDI) of
      30 antibiotics were made using alpha-cyano-4-hydroxycinnamic acid (HCCA), 2,5
      dihydroxybenzoic acid (DHB), 5,10,15,20-tetrakis(4-hydroxyphenyl)-21H,23H
      porphyrin and meso-tetra(N-methyl-4-pyridyl)porphyrin matrices. Most antibiotics
      generated intense protonated molecules in HCCA and DHB matrices, and sodium or
      potassium adduct ions in porphyrin matrices. Using sulfonamide antibiotics as
      model compounds, DHB was found to be the most suitable matrix for quantitative
      analysis. Detection limits were about 1 picomole. Linear correlation (R2 > 0.97),
      between the sample quantity over the range 1 to 100 picomole and the signal
      response, was obtained when ratios of the sum of peak areas of protonated
      molecules and sodium adduct ions, with reference to that of a structurally
      analogous internal standard (acetaminophen), were measured. The precision was
      found to be in the range of 4 to 32% relative standard deviation, dependent on
      the type and concentration of the analyte. A simple acylation derivatization
      process was developed to confirm the presence of suspected antibiotic residues.
      It is demonstrated that MALDI is a viable technique for the quantitative analysis
      of low molecular weight antibiotics.

PMID- 9534253
TI  - Cloning and disruption of the beta-isopropylmalate dehydrogenase gene (LEU2) of
      Pichia stipitis with URA3 and recovery of the double auxotroph.
AB  - Transformation of Pichia stipitis is required to advance genetic studies and
      development of xylose metabolism in this yeast. To this end, we used P. stipitis
      URA3 (PsURA3) to disrupt P. stipitis LEU2 in a P. stipitis ura3 mutant. A highly
      fermentative P. stipitis mutant (FPL-DX26) was selected for resistance to 5'
      fluoroorotic acid to obtain P. stipitis FPL-UC7 (ura3-3). A URA3:lacZ "pop-out"
      cassette was constructed containing PsURA3 flanked by direct repeats from
      segments of the lacZ reading frame. The P. stipitis LEU2 gene (PsLEU2) was cloned
      from a P. stipitis CBS 6054 genomic library through homology to Saccharomyces
      cerevisiae LEU2, and a disruption cassette was constructed by replacing the
      PsLEU2 reading sequence with the PsURA3:lacZ cassette. FPL-UC7 (ura3-3) was
      transformed with the disruption cassette, and a site-specific integrant was
      identified by selecting for the Leu- Ura+ phenotype. The ura3 marker was
      recovered from this strain by plating cells onto 5'-fluoroorotate and screening
      for spontaneous URA3 deletion mutants. Excision of the flanked PsURA3 gene
      resulted in the Leu- Ura- phenotype. The double auxotrophs are stable and can be
      transformed at a high frequency by PsLEU2 or PsURA3 carried on autonomous
      replication-sequence-based plasmids.

PMID- 9534255
TI  - Chromosomal polymorphism and adaptation to specific industrial environments of
      Saccharomyces strains.
AB  - Several industrial Saccharomyces strains, including bakers', wine, brewers' and
      distillers' yeasts, have been characterized with regards to their DNA content,
      chromosomal polymorphism and homologies with the DNA of laboratory strains.
      Measurement of the DNA contents of cells suggested that most of the industrial
      yeasts were aneuploids. Polymorphisms in the electrophoretic chromosomal pattern
      were so large that each strain could be individually identified. However, no
      specific changes relating to a particular group were observed. Hybridization
      using different probes from laboratory strains was very strong in all cases,
      indicating that all industrial strains possess a high degree of DNA homology with
      laboratory yeasts. Probes URA3, CUP1, LEU2, TRP1, GAL4 or ADC1 demonstrated the
      presence of one or two bands, two especially in bakers' strains. Also, results
      indicate that all hybridized genes are located on the same chromosomes both in
      laboratory and industrial strains. Translocation from chromosome VIII to XVI
      seems to have occurred in a distillers' strain, judging by the location of the
      CUP1 probe. Finally, when the SUC2 probe is used, results indicate a very
      widespread presence of the SUC genes in only bakers' and molasses alcohol
      distillers' strains. This clearly suggests that amplification of SUC genes is an
      adaptive mechanism conferring better fitness upon the strains in their specific
      industrial conditions. The widespread presence of Ty1 and Ty2 elements as well as
      Y' subtelomeric sequences could account for the inter- and intrachromosomal
      changes detected.

PMID- 9534254
TI  - An autoselection system in recombinant Kluyveromyces lactis enhances cloned gene
      stability and provides freedom in medium selection.
AB  - An autoselection system for increasing plasmid stability in Kluyveromyces lactis,
      based on the blockage of the pyrimidine de novo and salvage pathways, was
      investigated. In a manner analogous to that used in Saccharomyces cerevisiae, a
      putative "fur 1" mutation was selected in a uraA K. lactis strain using 5
      fluorouracil and 5-fluorocytosine plates. Survival of the mutant required
      expression of a plasmid-borne URA3 gene regardless of the culture medium
      employed, verifying the efficacy of this autoselection system in K. lactis. The
      expression of heterologous invertase, encoded by the S. cerevisiae SUC2 gene, was
      studied during long-term sequential batch cultures (70 generations) in complex
      yeast/peptone/glucose medium. The fur 1 mutant successfully retained the plasmid;
      invertase specific activity remained above 90% of the initial level. Furthermore,
      no mutation reversion was observed. In contrast, for the control non-fur 1
      strain, only 4% of the cells retained the plasmid after 70 generations, and
      invertase specific activity dropped to less than 10% of the initial level.
      Experiments comparing growth and activity in different media indicated the
      potential for improving productivity through medium enrichment using this
      autoselection system.

PMID- 9534256
TI  - Increased toxicity of modified mosquitocidal binary toxins of Bacillus sphaericus
      expressed in Escherichia coli.
AB  - The binary mosquitocidal genes of 51-kDa and 42-kDa proteins isolated from
      Bacillus sphaericus 1593 have been expressed at moderate levels in Escherichia
      coli employing the pQE expression system. The expressed proteins are readily
      visible in Coomassie blue-stained protein gels. The recombinant E. coli cells
      expressing toxic proteins were toxic towards Culex larvae. During the assembly of
      crystals in B. sphaericus, the 42-kDa toxin is first cleaved at the N-terminal
      end by a specific B. sphaericus protease. To express the toxins in E. coli the B.
      sphaericus specific protease-recognition site was deleted at the N-terminal end
      of the 42-kDa toxin, thereby mimicking the structure of the toxin as present in
      the crystal. This modification resulted in a twofold increase in the toxicity of
      the E. coli cells expressing the modified 42-kDa toxin as a constituent of the
      binary toxin. Our results demonstrate the utility of this modification for
      heterologous expression of the binary toxin genes from B. sphaericus.

PMID- 9534258
TI  - Beta-glycosidase (amygdalase and linamarase) from Endomyces fibuliger (LU677):
      formation and crude enzyme properties.
AB  - In our previous studies, the yeast Endomyces fibuliger LU677 was found to degrade
      amygdalin in bitter apricot seeds. The present investigation shows that E.
      fibuliger LU677 produces extracellular beta-glycosidase activity when grown in
      malt extract broth (MEB). Growth was very good at 25 degrees C and 30 degrees C
      and slightly less at 35 degrees C. When grown in MEB of pH 5 and pH 6 with
      addition of 0, 10 or 100 ppm amygdalin, E. fibuliger produced only slightly more
      biomass at pH 5, and was only slightly inhibited in the presence of amygdalin.
      Approximately, 60% of the added amygdalin was degraded (fastest at 35 degrees C)
      during an incubation period of 5 days. Supernatants of cultures grown at 25
      degrees C and pH 6 for 5 days were tested for the effects of pH and temperature
      on activity (using amygdalin, linamarin and prunasin as substrates). Prunase
      activity had two pH optima (pH 4 and pH 6), amygdalase and linamarase only one
      each at pH 6 and pH 4-5 respectively. The linamarase activity evolved earlier
      than amygdalase (2 days and 4 days respectively). The data thus indicate the
      presence of at least two different glycosidases having different pH optima and
      kinetics of excretion. In the presence of amygdalin, lower glycosidase activities
      were generally produced. However, the amygdalin was degraded from the start of
      the growth, strongly indicating an uptake of amygdalin by the cells. The
      temperature optimum for all activities was at 40 degrees C. Activities of
      amygdalase (assayed at pH 4) and linamarase (at pH 6) evolving during the growth
      of E. fibuliger were generally higher in cultures grown at 25 degrees C and 30
      degrees C. TLC analysis of amygdalin degradation products show a two-stage
      sequential mechanism as follows: (1) amygdalin to prunasin and (2) prunasin to
      cyanohydrin.

PMID- 9534257
TI  - Oat beta-glucan and xylan hydrolysates as selective substrates for
      Bifidobacterium and Lactobacillus strains.
AB  - Novel oligomers that resist digestion in the upper gut were prepared from oat
      mixed-linked beta-glucan and xylan by enzymatic hydrolysis with lichenase of
      Bacillus subtilis and xylanase of Trichoderma reesei respectively. The low
      molecular-mass hydrolysis products of beta-glucan and xylan were compared with
      fructooligomers and raffinose in their ability to provide growth substrates for
      probiotic (Lactobacillus and Bifidobacterium) and intestinal (Bacteroides,
      Clostridium and Escherichia coli) strains in vitro. A degradation profile of each
      carbohydrate and total sugar consumption were analysed with HPLC, and bacterial
      growth rate with an automatic turbidometer, the Bioscreen C system. beta
      Glucooligomers and xylooligomers both enhanced the growth of health-promoting
      probiotic strains as compared with intestinal bacterial growth, but not to a
      significant level. Raffinose stimulated the probiotic strains significantly,
      whereas fructooligomers induced high average growth for intestinal bacteria also.

PMID- 9534259
TI  - The effect of growth conditions on the biodegradation of tributyl phosphate and
      potential for the remediation of acid mine drainage waters by a naturally
      occurring mixed microbial culture.
AB  - The biodegradation of tributyl phosphate (Bu3-P, TBP), releasing phosphate at a
      high enough concentration locally to precipitate uranium from solution, was
      demonstrated by a mixed culture consisting primarily of pseudomonads. The effect
      of various parameters on Bu3-P biodegradation by growing cells is described.
      Growth at the expense of Bu3-P as the carbon and phosphorus source occurred over
      a pH range from 6.5 to 8, and optimally at pH 7. Bu3-P biodegradation was optimal
      at 30 degrees C, reduced at 20 degrees C and negligible at 4 degrees C and 37
      degrees C. Incorporation of Cu or Cd inhibited, and Ni, Co and Mn reduced its
      degradation. Inorganic phosphate (above 10 mM) and kerosene (up to 1 g/l) reduced
      Bu3-P biodegradation significantly, but nitrate had no effect. Sulphate (10-100
      mM) was inhibitory. When pregrown biomass was used the fastest rates of tributyl
      and dibutyl phosphate biodegradation were 25 mumol h-1 mg protein-1 and 37 mumol
      h-1 mg protein-1 respectively. Microcarrier-immobilised biomass decontaminated
      uranium-bearing acid mine waste water by uranium phosphate precipitation at the
      expense of Bu3-P hydrolysis in the presence of 35 mM SO(4)2-. At pH 4.5, 79% of
      the UO2(2)+ was removed at a flow rate of 1.4 ml/h on a 7-ml.test column.

PMID- 9534260
TI  - Treatment of cyanide-containing wastewater from the food industry in a laboratory
      scale fixed-bed methanogenic reactor.
AB  - During the process of producing cassava starch from Manihot esculenta roots,
      large amounts of cyanoglycosides were released, which rapidly decayed to CN-
      following enzymatic hydrolysis. Depending on the varying cyanoglycoside content
      of the cassava varieties, the cyanide concentration in the wastewater was as high
      as 200 mg/l. To simulate anaerobic stabilization, a wastewater with a chemical
      oxygen demand (COD) of about 20 g/l was prepared from cassava roots and was
      fermented in a fixed-bed methanogenic reactor. The start-up phase for a 99%
      degradation of low concentrations of cyanide (10 mg/l) required about 6 months.
      After establishment of the biofilm, a cyanide concentration of up to 150 mg CN-/l
      in the fresh wastewater was degraded during anaerobic treatment at a hydraulic
      retention time of 3 days. All nitrogen from the degraded cyanide was converted to
      organic nitrogen by the biomass of the effluent. The cyanide-degrading
      biocoenosis of the anaerobic reactor could tolerate shock concentrations of
      cyanide up to 240 mg CN-/l for a short time. Up to 5 mmol/l NH4Cl (i.e. 70 mg N/l
      = 265 mg NH4Cl/l) in the fresh wastewater did not affect cyanide degradation. The
      bleaching agent sulphite, however, had a negative effect on COD and cyanide
      removal. For anaerobic treatment, the maximum COD space loading was 12 g l-1 day
      1, equivalent to a hydraulic retention time of 1.8 days. The COD removal
      efficiency was around 90%. The maximum permanent cyanide space loading was 50 mg
      CN- l-1 day-1, with tolerable shock loadings up to 75 mg CN- l-1 day-1. Under
      steady-state conditions, the cyanide concentration of the effluent was lower than
      0.5 mg/l.

PMID- 9534261
TI  - [Proceedings of the VII Teaching Conference on Family and Community Medicine and
      XVII National Congress on Family and Community Medicine].

PMID- 9534262
TI  - 4-aryl-5-oxo-1,2,3,4,5,6,7,8-octahydroquinazoline-2-thione derivatives:
      synthesis, enantiomeric separation and in vitro screening as calcium antagonists.
AB  - Fourteen new 4-aryl-5-oxo-1,2,3,4,5,6,7,8-octahydroquinazoline-2-thione
      derivatives were synthesized and screened in vitro for their calcium antagonistic
      activities. The compounds were prepared by reacting 1,3-cyclo-hexanedione with
      appropriate aromatic aldehydes and thiourea under modified Biginelli reaction
      conditions. The structures of the compounds were proved by IR, 1H-NMR, mass
      spectroscopy and elemental analysis. The compounds synthesized exerted calcium
      antagonistic action on smooth musculature by inhibiting BaCl2-induced
      contractions of isolated rat ileum. It was found that compound 12l having 3
      methoxyphenyl group at the 4th position was the most potent compound in this
      series (pEC50: 4.00 +/- 0.20). Rasemic compound 12l was resolved into its
      enantiomers by high performance liquid chromatography (HPLC) using a commercially
      available cellulose tris(p-methylbenzoate) chiral stationary phase, known as
      Chiralcel OJ. The enantiomeric ratio was validated and peak identification for
      each enantiomer was established according to their optical rotation sign.

PMID- 9534265
TI  - Solubility and stability of indomethacin in sodium acetate solution. A
      consideration of hydrotropic mechanism.
AB  - The effect of sodium acetate on the aqueous solubility of indomethacin was
      studied. Increases in solubility were associated with the presence of sodium
      acetate in the dissolution medium. The mechanism of solubilisation was considered
      in relation to the possible effects of highly water-soluble substances on the
      structure of water. Thermodynamic conditions associated with the interactions
      were found to be favourable to the proposed mechanism. However, indomethacin was
      hydrolytically unstable in the solubilised state.

PMID- 9534263
TI  - 2-methyl-3-acetyl-4-aryl-5-oxo-1,4-dihydro-5H indeno(1,2-b) pyridine derivatives
      studies and their calcium antagonistic activities.
AB  - Sixteen 2-methyl-3-acetyl-4-aryl-5-oxo-1,4-dihydro-5H-indeno(1,2-b)pyridine
      derivatives (3a-p) have been prepared. The structures of the compounds were
      characterised by IR, 1H-NMR, 13C-NMR, X-Ray and elemental analyses. The calcium
      antagonistic activity of these compounds were studied in rat taenia coli pre
      contracted with 1 mmol/l Ca+2.

PMID- 9534266
TI  - The pharmacological effects of some 1H-1,4-benzothiazineylide derivatives on the
      cardiovascular system of the rat and some smooth muscles.
AB  - A series of 1H-1,4-benzothiazineylides was synthesized and characterized. The
      influence of this series of compounds 1-7 was examined on the cardiovascular
      system of the rat, the isolated jejunum of the rabbit, the guinea-pig ileum and
      the isolated uteri of late pregnant rats. The results of the present study
      revealed the bradicardiogenic effect of the ethyl, propyl and isobutyl
      derivatives when tested in the dose range of (10-53 mumole Kg-1). Furthermore,
      the isobutyl derivative also exhibited an ability to decrease the arterial blood
      pressure. All the test compounds exhibited non-spasmolytic activity against ACh,
      histamine and BaCl2. The butyl, isobutyl and isopropyl derivatives were found to
      be the most potent. The results direct the attention to a new potential group of
      cardiovascular depressant and spasmolytic agents.

PMID- 9534267
TI  - [Is it possible (and desirable) to administer a standard for an effective health
      policy for the European Union?].
AB  - The European Union has a formal interest in public health under the Article 129
      of the Maastricht Treaty. Hitherto, the main contribution of the European Union
      action in public health has been limited to research, health information and
      education concerning, in particular major diseases and drug dependence.
      Unfortunately the European architects did not clearly conceive a plan for the
      establishment of a common health policy despite the fact that the European health
      policies are fragmented and are often the indirect results of economic policies.
      Indeed, the domain of public health is essentially governed by the principle of
      national sovereignty, onto which the principle of subsidiarity has been grafted.
      Whereas Article 129 of the Maastricht Treaty applies especially to preventive
      health policies, the concomitant affirmation of the principle of subsidiarity in
      this field tends to suspend any establishment of a European health policy. In the
      same way, the lack of compulsory provisions relating to Community actions,
      expressed as recommendations, raises the question whether the European Union is
      willing to move to a European health policy.

PMID- 9534268
TI  - [The neuropathies of IgM monoclonal gammopathies].
AB  - A peripheral polyneuropathy is often associated with an IgM monoclonal
      gammapathy. The monoclonal protein often binds to carbohydrate epitopes on
      glycoproteins and/or glycolipids of the human peripheral nerve. The clinical
      syndrome is related to the antigen-specificity of the IgM protein. Detection of
      anti-myelin antibodies and further characterization of their immunogenic
      specificity provide an important aid in the differential diagnosis of late-onset
      chronic polyneuropathies.

PMID- 9534269
TI  - [Factor V Leiden and thrombophilia].

PMID- 9534270
TI  - [Lacunar cerebral lesions and vascular risk factors].
AB  - Since their detailed description by Fisher, lacunar strokes are known to have
      particular clinical presentations, etiologies and prognostic implications. Small
      artery disease is at the origin of most lacunes and was classically believed to
      be mainly due to hypertension. Recent studies have shown no differences in the
      prevalence of hypertension in patients with lacunar infarction compared to
      patients with non-lacunar infarction. Vascular risk factors may be different in
      single versus multiple lacunes and in the presence or absence of leukoaraiosis.
      The association of several risk factors in an individual patient probably also is
      of major importance for the development of small artery disease. Further studies
      on the risk factors for lacunes should separate single from multiple lacunes and
      carefully analyze the different patterns of risk association.

PMID- 9534271
TI  - [Adenosarcoma and other uterine sarcomas].
AB  - Sarcomas are tumors of conjunctive origin, rarely relating to the gynaecological
      sphere; among these, the adenosarcoma only represent one particular aspect. From
      one clinical case and from literature, the authors attempt to sum up the
      situation on the different clinical, para-clinical and therapeutic aspects of
      those bad-know neoplasia.

PMID- 9534272
TI  - [Current developments in the laboratory diagnosis of rubella].
AB  - Thirty years after the introduction of the hemagglutination inhibition assay
      (HAI), laboratory diagnosis of rubella virus infection has achieved a high
      reliability. While the HAI remains the reference standard against which newer
      assays are compared, routine laboratory diagnosis is based mainly on ELISA tests
      which permit a more rapid and less cumbersome detection of specific IgG and IgM
      antibody. Although quantification of immunoglobulin G against rubella virus is
      performed using WHO standards, the correlation between different ELISAs is
      relatively poor. Despite substantial improvements in virus isolation and nucleic
      acid amplification techniques, serology remains the mainstay of diagnosis for
      both acquired and postnatal diagnosis of congenital infection. Differentiation
      between primary and re-infection is of critical importance during pregnancy and
      can be achieved relatively reliably by antibody avidity determination or by
      immunoblot. While current anti-rubella IgM ELISAs are relatively sensitive, their
      specificity may be limited by cross reactivity with other viruses, i.e.
      parvovirus B19 and Epstein-Barr virus. Maternal reinfection with congenital
      rubella syndrome is very rare, however it may be misdiagnosed in the absence of
      significant IgG antibody titer change and/or IgM antibody.

PMID- 9534273
TI  - [Will we all be poisoned?].
AB  - Since several years there is a great concern in the general population, that all
      people will be poisoned by food additives, drug and pesticide residues in food
      and by environmental pollution. There is a great confusion about the real risk
      due to these issues. The author tries to explain these misunderstandings by some
      typical examples. Toxicity testing procedures used for the evaluation of chemical
      safety are enumerated. Misinterpretation of experimental studies and epidemiology
      studies are at the origin of these fears. Except for acute industrial accidents,
      suicide attempts and drug abuse the risk of poisoning is rather low. Often the
      excellent performances of modern analytical technologies are at the origin of
      many incorrect conclusions. The concept of acceptable daily intake, safety
      factors, relative risks of deaths and other safety issues are discussed.

PMID- 9534274
TI  - [Ischemic preconditioning. We can still be faithful to the past].

PMID- 9534276
TI  - [Quantitative coronary angiography].

PMID- 9534275
TI  - [The role of hemostatic factors in atherogenesis].

PMID- 9534277
TI  - Helicobacter pylori infection and ischaemic heart disease.

PMID- 9534278
TI  - Skeletal muscle in heart failure.

PMID- 9534279
TI  - [Insulin and arterial hypertension].

PMID- 9534280
TI  - Determinants of the pulmonary artery pressure rise in left ventricular
      dysfunction.
AB  - Pulmonary artery hypertension in patients with left ventricular dysfunction is
      related to poor outcome but the role of cardiac functional abnormalities in the
      genesis of pulmonary hypertension remains unknown. The aim of this prospective
      study was to identify the determinants of pulmonary hypertension in 102
      consecutive patients with primary left ventricular dysfunction (ejection fraction
      < 50%). Systolic pulmonary artery pressure was measured by continuous wave
      Doppler. Left ventricular systolic and diastolic function, severity of functional
      mitral regurgitation, cardiac output, and left atrial volume were assessed using
      Doppler echocardiography. In patients with left ventricular dysfunction, systolic
      pulmonary artery pressure was increased (51 +/- 14 mmHg, range 23 to 87 mmHg).
      Mitral deceleration time (r = -0.61; p = 0.0001) and mitral effective regurgitant
      orifice (r = 0.50; p = 0.0001) were the strongest parameters related to systolic
      pulmonary artery pressure. Multivariate analysis identified these two variables
      as the strongest predictors of systolic pulmonary artery pressure in association
      with the mitral E/A ratio (p = 0.006) and age (p = 0.005). In conclusion,
      pulmonary hypertension is common and variable in patients with left ventricular
      dysfunction. It is closely related to diastolic dysfunction and severity of
      functional mitral regurgitation but not independently to the degree of left
      ventricular systolic dysfunction. These findings underline the importance of
      assessing diastolic function and quantifying mitral regurgitation in patients
      with left ventricular dysfunction.

PMID- 9534281
TI  - [Improvement of accessory pathways radiofrequency catheter ablation by arterial
      or venous epicardial mapping].
AB  - Failure of radiofrequency catheter ablation for atrioventricular reciprocating
      tachycardia may be related to imprecise location of accessory pathways. We have
      tested the safety and efficacy in improving successful rate of the procedure of a
      new technique of epicardial mapping of the atrioventricular sulcus by means of a
      small diameter (2.5F) 16 polar electrode catheter with a soft tip and a minor
      interelectrode and intercouple distance (2-6-2). The catheter was advanced via a
      right femoral approach into the coronary sinus or its branches, and the right
      coronary artery. We report 5 patients who underwent epicardial mapping-guided
      radiofrequency catheter ablation who had been previously treated with 1 or more
      (range 1-4) unsuccessful traditional mapping of the atrioventricular sulcus.
      Epicardial mapping was performed by means of selective catheterization of the
      coronary sinus in 4 cases, and of the right coronary artery in 1. The accessory
      pathways was precisely localized and ablated in all patients (mean 8 +/- 1.5
      radiofrequency pulses, and 32 +/- 6 min fluoroscopy duration). No procedure or
      catheterization-related complications were observed. In conclusion, the technique
      of epicardial mapping used in this study proved to be safe and effective in
      localizing accessory pathways in selected cases, thereby enhancing radiofrequency
      catheter ablation success rate. The main advantage of this atraumatic catheter as
      compared to the traditional ones are the femoral approach and the possibility to
      advance the catheter to the most anterior aspect of the great cardiac vein. The
      epicardial mapping is thus a feasible alternative to traditional mapping,
      particularly in cases in which previous procedures have failed due to a complex
      arrhythmogenic substrate and or congenital abnormalities.

PMID- 9534282
TI  - [The difference between clinical ambulatory measured blood pressure and daily
      monitored pressure does not reflect the "white coat effect"].
AB  - The difference between clinic and average daytime ambulatory blood pressure is
      frequently used to identify patients with "white coat" hypertension (i.e. with a
      pronounced pressor response to the clinical evaluation) although there is no
      evidence that this difference is indeed due to a white coat effect. In 28 mild
      hypertensive outpatients, the blood pressure was continuously recorded by a
      noninvasive finger device before and during the doctor's visit. The peak blood
      pressure increase, recorded during the visit was compared with the difference
      between clinic and daytime average ambulatory blood pressure. Peak increases in
      systolic and diastolic finger blood pressure during the doctor's visit were 38.2
      +/- 3.1 mmHg and 20.7 +/- 1.6 mmHg, respectively compared to pre visit values
      (means +/- standard error, both p < 0.01). Daytime average systolic and diastolic
      blood pressure were 135.5 +/- 2.5 mmHg and 89.2 +/- 1.9 mmHg, both being lower
      than the corresponding clinic blood pressure values (146.6 +/- 3.6 mmHg and 94.9
      +/- 2.2 mmHg, p < 0.01). Their differences, however, were < 30% of the peak
      finger blood pressure increase during the physician's visit. While the
      physician's visit was associated with tachycardia (+9.0 +/- 1.6 b/min, p < 0.01)
      there was no difference between clinic and daytime average heart rate. The
      alerting reaction and the pressor response induced by the physician's visit is
      not reflected by the difference between clinic and daytime average blood
      pressure. Such a difference is not therefore a reliable measure of the white coat
      effect.

PMID- 9534283
TI  - Influence of autonomic tone on QT interval duration.
AB  - The autonomic tone has been shown to influence the duration of the QT interval,
      however the independent contribution of sympathetic and parasympathetic tone is
      not fully elucidated. The influence of autonomic tone on QT duration was studied
      in 10 young healthy volunteers by evaluating the changes in QT and RR duration
      induced by i.v. isoproterenol infusion and by standing before and after i.v.
      administration of propranolol or atropine. Furthermore, the relationship between
      RR interval and QT duration was evaluated during nocturnal sinus arrhythmia and
      submaximal exercise test. Low doses of isoproterenol reduced RR (p < 0.01) but
      not QT interval duration, while higher doses influenced both RR (p < 0.0001) and
      QT (p < 0.001) duration. Propranolol did not influence standing-induced
      shortening of RR and QT intervals; on the contrary, atropine administration
      abolished standing-induced QT interval shortening, without influencing RR
      changes. QT duration resulted significantly related to preceding RR interval at
      peak exercise (r = 0.87, p < 0.001) and during nocturnal sinus arrhythmia (r =
      0.73, p < 0.0005), however, the regression lines showing the correlation between
      QT and preceding RR interval were different. Both sympathetic and parasympathetic
      tone appear to contribute to heart rate-independent changes in QT duration. In
      the basal state parasympathetic more than sympathetic tone influences the
      relation QT-heart rate. Major increases of sympathetic nervous system activity
      may change the relation QT-heart rate. Thus, in case of abrupt autonomic changes,
      any proposed formula for heart rate correction of QT may result inappropriate,
      also in the normal range of heart rate.

PMID- 9534284
TI  - Effect of training program based on anaerobic threshold in the early phase after
      acute myocardial infarction.
AB  - We devised a new physical training program on the basis of anaerobic threshold
      for rehabilitation in the early phase of acute myocardial infarction. Forty-four
      patients were divided into two groups, control and training. We measured the left
      ventricular ejection fraction using nuclear stethoscopy during the treadmill test
      and calculating radioactive cardiac output. In the training group, anaerobic
      threshold and exercise time to the anaerobic threshold point were significantly
      increased, and stroke volume at rest measured by the dye dilution method
      increased significantly. Radioactive cardiac output during exercise also
      increased after the exercise therapy. These results indicate that the
      rehabilitation program consisting of physical training based on the anaerobic
      threshold is effective.

PMID- 9534285
TI  - [Pacemaker-induced infection: diagnosis by multi-plane transesophageal
      echocardiography].
AB  - We report the identification by multiplane transesophageal echocardiography of a
      vegetation on a permanent pacemaker lead in a patient with persistent
      bacteriemia. The lesion could not be visualized with transthoracic
      echocardiography. The diagnosis of vegetation was based on the visualization of a
      freely highly mobile mass attached to the pacemaker lead, with different
      echogenicity from the lead. The entire pacing system was surgically removed
      through a right atrial approach, and inspection confirmed pacemaker lead
      vegetation. We conclude that transesophageal echocardiography should be
      considered to investigate suspected pacemaker lead infection in patients with
      negative transthoracic echocardiography.

PMID- 9534286
TI  - [The hematologist].

PMID- 9534287
TI  - [Inhibitors of platelet receptors in the cardiac catheterization laboratory: from
      a biological chimera to a clinical reality].

PMID- 9534288
TI  - [The development of surgical treatment for hypoplastic left heart syndrome].

PMID- 9534289
TI  - [Endothelial control of coronary circulation].

PMID- 9534290
TI  - Diuretics in the management of congestive heart failure.

PMID- 9534291
TI  - [The effect of early or late patency of vascular necrosis on the phenomenon of
      postinfarct ventricular remodeling].

PMID- 9534292
TI  - Exercise and coronary artery disease prevention.
AB  - Physical exercise has become universally accepted as an important component in
      the primary prevention of coronary disease and in the management of subjects with
      established coronary artery disease. Exercise should be utilized appropriately
      for each individual's needs and done in concert with aggressive modification of
      other risk factors such as abnormal blood lipids, high blood pressure, obesity
      and cigarette smoking. Such as approach in the preventive management of coronary
      artery disease is rewarded by beneficial clinical outcomes and savings in health
      dollars.

PMID- 9534293
TI  - [The effectiveness and tolerability of losartan and effect on left ventricular
      mass in patients with essential hypertension].
AB  - The purpose of our study was to evaluate the antihypertensive efficacy,
      tolerability and effects on left ventricular mass of losartan over 10 months in
      patients with essential hypertension. Losartan is a selective angiotensin II
      receptor-antagonist. The whole study comprised 89 hypertensive patients who were
      randomized, at baseline, to 10 months of double-blind once daily treatment with
      losartan 50 mg (L Group, n = 49, mean age 55 +/- 13 years) or hydrochlorothiazide
      25 mg (HCTZ Group, n = 40, mean age 56 +/- 10 years). Routine hematology, blood
      chemistry and urinalysis were performed before and after 5 and 10 months;
      standard electrocardiography, ambulatory non invasive 24-hours blood pressure
      monitoring, M-mode echocardiography, psychometric test and quality of life
      evaluation were obtained from all the patients before and after 10 months. In
      patients non responding after 4 weeks, hydrochlorothiazide 25 mg or losartan 50
      mg was added in the L Group and in the HCTZ Group, respectively (L-HCTZ Group).
      The results showed good tolerability and a significant mean systolic and
      diastolic blood pressure reduction in all groups (L Group from 157/96 +/- 9/7 to
      137/85 +/- 9/5 mmHg, p < 0.001; HCTZ Group from 158/97 +/- 11/8 to 150/91 +/- 9/7
      mmHg, p < 0.003; L-HCTZ Group from 159/98 +/- 9/5 to 141/88 +/- 6/4 mmHg, p <
      0.001), although L and L-HCTZ treatment were more effective during 24 hours than
      HCTZ. Moreover, a remarkable reduction in left ventricular mass index was
      obtained after 10 months only in the L Group (from 138.4 +/- 26.2 to 127.2 +/-
      23.1 g/m2, p < 0.04) and in the L-HCTZ Group (from 140 +/- 20.3 to 125.5 +/- 20.1
      g/m2, p = 0.126). Finally, in patients treated with losartan the results of
      psychometric test significantly improved (L Group: p < 0.05; L-HCTZ Group: p <
      0.05) and a positive remarkable change in the quality of life was observed (L
      Group: p < 0.05; L-HCTZ Group: p = 0.083). In conclusion, losartan in monotherapy
      or in association with hydrochlorothiazide, was well tolerated, respected the
      quality of life, and produced a significant and remarkable reduction in blood
      pressure and left ventricular mass in hypertensive patients.

PMID- 9534294
TI  - [An aggressive exercise test is suitable for myocardial scintigraphy].
AB  - Exercise myocardial scintigraphy is frequently used as a second step tool in the
      assessment of coronary artery disease. Little attention has been paid on the
      exercise protocol used as a stress during scintigraphy. However, the diagnostic
      accuracy of the test is better if higher heart rate is achieved. The aim of this
      study was to evaluate if an aggressive exercise protocol was safe and more
      effective than a standard protocol in achieving higher heart rate. Eighty-four
      patients (64 men and 20 women, mean age 56 +/- 10 years, range 34-78 years)
      underwent a standard exercise test (cycloergometry; SET: 25 W increments every 2
      min starting from 25 W load) and an aggressive exercise test (AET: 50 W
      increments every 2 min starting from 50 W load); during AET a myocardial
      scintigraphy (Tc-99m sestamibi; SPECT) was performed. Heart rate and blood
      pressure were monitored during the tests and the rate-pressure product was
      calculated. No patients had major adverse events during either tests. During AET
      with respect to the SET, higher maximal heart rate (142 +/- 15 vs 134 +/- 16
      b/min; p < 0.01) and rate-pressure product (27,293 +/- 4341 vs 25,773 +/- 6690
      b/min x mmHg; p < 0.05) were obtained. During AET higher number of maximal (55/84
      vs 34/84; p < 0.05) and positive tests (45/84 vs 29/84; p < 0.05) were detected
      with respect to the SET. Using myocardial scintigraphy as a reference test, the
      diagnostic accuracy of the SET and AET was 54 and 73% respectively. In
      conclusion, an aggressive protocol during exercise stress test can safely be used
      to obtain a greater number of maximal and positive exercise tests.

PMID- 9534295
TI  - [Treatment aspects of unstable angina. Costs and payments for DRG].
AB  - Patients with unstable angina fall into a wide prognostic and therapeutic
      spectrum but, in general, have great access to specialty care and invasive
      procedures. In the modern era, in which admissions for unstable angina outnumber
      those for myocardial infarction, and growing economic pressures are placed on
      health care systems, cardiologists must re-examine clinical strategies for
      treating unstable angina in the light of health-cost accounting. The aims of the
      present study were to examine the current management of patients admitted to our
      cardiology department and to calculate the medical costs. A patient schedule was
      drawn up to prospectively register the number and type of cardiac processes
      carried out during hospitalization for all unstable angina patients in the period
      between March 1st and May 30th, 1995. Time (minutes) actually spent by both
      physicians and nurses for each cardiac process were carefully recorded in order
      to calculate the activity budget. The effective economic budget was built for
      each cardiac process taking into account salaries, consumable supplies, equipment
      service contracts, depreciation and indirect medical and non medical costs for
      CCU and ward. Based to the Diagnosis Related Groups (DRG) system, 53 out of 318
      patients (16%) were admitted with documented or suspected unstable angina and
      allocated to discharge into four DRGs: DRG 140-medically treated unstable angina:
      18 patients; DRG 124-unstable angina with angiography: 16 patients; DRG 122
      unstable angina evolving in myocardial infarction: 6 patients; DRG 112-unstable
      angina with angioplasty: 13 patients. The mean cost for hospitalized patient with
      unstable angina was 5,574,958 Italian Liras (DRG 140 = 2,687,719; DRG 124 =
      2,800,347; DRG 122 = 6,086,563; DRG 112 = 12,751,454). The difference in costs
      was essentially related to the procedures involved in medical care, DRGs with
      expensive cardiac processes having higher costs. Furthermore, these data show a
      deep discrepancy between "real" costs and current DRG reimbursement. In
      conclusion, data show the standard management of unstable angina at our center;
      calculating the true costs of unstable angina is the first step towards
      maximizing resources and optimizing benefits.

PMID- 9534296
TI  - The collateral coronary circulation in the human fetus: angiographic findings.
AB  - Collateral circulation was studied in the heart of 20 normal human fetuses aged
      19 to 39 weeks, using a radiographic technique. The radiograms showed the
      presence of coronary anastomoses ranging in size from 3 to 50 mu. The anastomoses
      were more abundant and of larger diameter in the interventricular septum and in
      the subendocardial layers. Anastomoses between the superficial vessels were also
      present but were less frequent and of smaller diameter.

PMID- 9534297
TI  - [The role of 4G/5G polymorphism in the regulation of plasma levels of PAI-1: a
      model of interaction between genetic and environmental factors].
AB  - Previous studies have suggested that a decreased fibrinolytic potential can play
      a role as risk factor for thrombotic events. Blood levels of factors of the
      fibrinolytic system are highly heritable, supporting the importance of the
      genetic background. To better understand the impact of two common polymorphisms
      of the tissue-type plasminogen activator (t-PA) and plasminogen activator
      inhibitor-1 (PAI-1) genes on the in vivo regulation of fibrinolysis, we have
      studied this genetic variables together with other clinical and metabolic factors
      in a sample of the Italian population. Two hundred-eighteen subjects without
      history of atherothrombosis or mayor diseases entered the study. A detailed
      clinical history was collected and evaluations of blood levels of cholesterol,
      triglycerides, PAI-1 activity, PAI-1 antigen, t-PA activity, t-PA antigen were
      performed on standard conditions. Genotypes at the locus of the 4G/5G
      polymorphism of PAI-1 gene promoter and at locus of the insertion/deletion Alu
      repeat polymorphism of t-PA gene intron h were studied. No detectable effect was
      found for the t-PA gene polymorphism in our population. On the other hand, the
      4G/5G polymorphism was found to modulate plasma PAI-1 activity levels and the
      interaction between PAI-1 plasma activity levels and blood lipids. Moreover, such
      regulation by genotype was found to be affected by the presence or absence of
      dyslipidemia. In conclusion, our findings suggest that, among subjects with or
      without metabolic disorders such as dyslipidemia, completely different gene
      environment interactions may occur, and could affect the individual risk of
      thrombosis.

PMID- 9534298
TI  - [Anomalous origin of the sinus node artery from the left main trunk: a potential
      cause of iatrogenic hypokinetic arrhythmia].
AB  - The sinus node artery (SNA) arises from the right coronary artery in near 60% of
      the cases and from the left circumflex artery in the remaining ones. We described
      the case of a patient in whom the SNA took off from the proximal part of the left
      main trunk. A 59 year-old male underwent coronary arteriography because of
      unstable angina. Soon after the incannulation of the left coronary ostium with a
      7F catheter critical bradycardia ensued without ECG changes of ischemia. The
      arrhythmia spontaneously reverted by removing the catheter. Further contrast
      injections were carried out with a smaller diagnostic catheter (5F); the left
      main trunk was normal with the SNA arising from the very proximal part of it. It
      is likely that the heart rate slowing was elicited by a temporary occlusion (and
      related ischemia) of the anomalous SNA by the diagnostic catheter. This anomaly
      may therefore provoked heart arrhythmias during diagnostic or interventional
      procedures.

PMID- 9534299
TI  - [Neurocardiology: developmental history].

PMID- 9534300
TI  - [Neurology].

PMID- 9534301
TI  - [Myocardial revascularization: a treatment measured for each patient].

PMID- 9534302
TI  - [The physiology of circulation during cardiopulmonary resuscitation: background
      for the use of new resuscitation techniques].

PMID- 9534303
TI  - [Preoperative evaluation and anesthesia administration in candidate cardiopathy
      patients for non-cardiosurgical intervention].

PMID- 9534304
TI  - [The role of transcatheter ablation for the treatment of atrial fibrillation].

PMID- 9534305
TI  - C-reactive protein response and progression of atherosclerosis: is
      atherosclerosis the byproduct of systemic infection?

PMID- 9534306
TI  - Chlamydia pneumoniae and cardiovascular disease.

PMID- 9534307
TI  - [Peri-infarct angiographic behavior of "non-culprit" coronary infarct lesions].
AB  - Because systemic factors, such as lipoproteins, autoantigens, infectious agents,
      may facilitate plaque rupture, thrombus formation and coronary occlusion, the
      question may arise of whether thrombosis be only a local plaque event or the
      consequence of an acute activity of the entire coronary tree. Taking changes at
      the narrowest point of non culprit lesions as reflecting progression or
      regression of the disease when > 0.27 mm, early (within a few days) and late
      (within 1 month) coronarographic findings in 23 patients with first infarction
      were compared with those of patients with stable angina, in whom coronary
      angiography was performed for diagnostic purposes and was repeated 1 month later,
      before angioplasty. Sixteen infarction patients had progression, 4 had
      regression, 1 had both, and 2 had steadiness; corresponding values in stable
      angina group were 2 (p < 0.001), 1 (NS), 0 (NS) and 20 (p < 0.001). In the
      infarction group, 17 out of the 45 non culprit lesions progressed and 5
      regressed; corresponding figures in stable angina group were 2 (p < 0.001) and 1
      (p < 0.05). Three of the infarction patients developed interim angina at rest
      that was associated with progression of a culprit lesion in each of them. These
      results support the hypothesis that in a number of cases infarction may not
      reflect an arbitrary plaque event but rather a systemic coronary disease activity
      with maximal expression at the level of the offending plaque.

PMID- 9534308
TI  - [Three dimensional reconstruction in intracoronary echography: a new system with
      automatic contour definition of ecg-gated image acquisition].
AB  - The use of a new automated contour-detection system (CD) allows rapid
      quantification of the dimensions of coronary lumen and plaque in an entire three
      dimensional set of intracoronary images (ICUS), obtained during an ECG-gated pull
      back image acquisition. The aim of the study was to evaluate the reproducibility,
      feasibility and accuracy of this approach in the clinical setting. We examined 32
      coronary stents implanted in 28 patients, mean age 59 +/- 16 years. The ICUS
      images were acquired during a motorized uniform-speed pull-back (0.5 mm/s) of the
      ultrasound catheter after angiographically guided stent optimization, recorded on
      videotape, and analyzed during a conventional two-dimensional ICUS examination.
      An ECG-gated pull-back was then performed and analyzed by a second operator using
      CD. The minimal lumen area and diameter of the stent and the lumen area of the
      reference segments were measured. Comparing the analysis on- and off-line,
      correlation coefficients (r) not less than 0.96, with a mean difference not
      higher than 0.3 +/- 1.5 were found. On the other side, the comparison between the
      two-dimensional analysis and the analysis performed on-line showed a good
      correlation between the two methods. The two-dimensional method revealed a
      systematic overestimation (delta = -1.3 +/- 2.3) of the area and diameter. The
      time required for the on-line three-dimensional analysis was 9 +/- 3 min, whereas
      the off-line analysis was performed within 35 +/- 10 min. Focal segments of stent
      underexpansion were seen in 4 cases by two-dimensional ICUS and in 3 more cases
      by three-dimensional ICUS, analyzed on- and off-line. In order to evaluate the
      reproducibility of the system, we examined ICUS images after an ECG-gated pull
      back of 23 segments of coronary arteries in 20 patients. The intra and
      interobserver variability was evaluated. The mean relative difference between the
      area and volume measurements of intra and interobserver variability ranged from
      0.14 to 1.51%, with a standard deviation not higher than +/- 7.17, a standard
      error of estimate not higher than +/- 4.85 and a correlation coefficient (r) not
      less than 0.98. Thus, the "contour detection" in ECG-gated three-dimensional ICUS
      is highly reproducible, suggesting the use of the system in studies of
      progression-regression of atherosclerosis. It is feasible for the on-line
      application as it can be performed rapidly and shows good agreement with
      measurements obtained by off-line CD.

PMID- 9534309
TI  - Hexarelin, a growth hormone-releasing peptide, discloses protectant activity
      against cardiovascular damage in rats with isolated growth hormone deficiency.
AB  - The ability of hexarelin, a recently synthesized hexapeptide with a remarkable
      growth hormone (GH)-releasing activity, to reverse signs of cardiovascular
      dysfunction in GH-deficient animals was studied in young male rats made GH
      deficient by the administration of an anti-GH-releasing hormone serum (GHRH-Ab)
      for 20 days. Heart preparations from GHRH-Ab treated rats, subjected to low-flow
      ischemia and reperfusion, showed: a progressive increase of left ventricular end
      diastolic pressure during the ischemic period and a poor recovery of
      contractility at reperfusion as compared to control hearts; a decreased rate of
      formation of 6-keto-PGF1 alpha, the stable metabolite of prostacyclin, in
      perfusates of both preischemic and reperfusion period; an increased vasopressor
      activity of angiotensin II on the coronary vasculature. The endothelium-dependent
      relaxing function in GH-deficient rats was also evaluated in aortic ring
      preparations, which showed: a decreased rate of formation of 6-keto-PGF1 alpha,
      an hyperreactivity to endothelin-1, a markedly reduced vasopressor response to NG
      monomethyl-L-arginine (the nitric oxide synthase inhibitor) and a decreased
      vasodilator response to acetylcholine of precontracted aortic tissue. Hexarelin
      (80 micrograms/kg, s.c. twice daily), administered for 15 days to GHRH-Ab-treated
      rats, fully restored the somatotropic function and reversed all the signs of
      cardiac and endothelial dysfunction. In fact, in heart preparations from rats
      treated with hexarelin the trend of the ischemic damage was similar to that
      observed in control rats and both the rate of formation of 6-keto-PGF1 alpha and
      the vasopressor activity of angiotensin II were reverted to control levels.
      Furthermore, all the parameters of endothelial function were in the normal range.
      These results indicate that GH deficiency in rats is responsible for an
      impairment of cardiac function that is associated with a damage of the
      endothelium-dependent relaxing function not limited to coronary vessels but
      widespread in the circulation. These alterations are fully reverted by an in vivo
      treatment with hexarelin.

PMID- 9534310
TI  - [Endothelium-protective effects of epinine (N-methyldopamine) in myocardial
      ischemia-reperfusion in the isolated working rat heart].
AB  - The effect of cardiac dopaminergic receptors stimulation with epinine (N
      methyldopamine) on reperfusion injury was investigated in isolated working rat
      heart submitted to 15 min of global ischemia. Isolated Wistar rat hearts (n = 75)
      were used and subdivided into five groups: Group A control hearts, Group B
      epinine 10 ng/ml, Group C epinine 20 ng/ml, Group D epinine 40 ng/ml, Group E
      epinine 80 ng/ml. The drug was added to the perfusion buffer at the beginning of
      experimental procedures. Hemodynamic parameters, heart rhythm (epicardial ECG),
      heart weight changes, coronary microvascular permeability (FITC-albumin
      diffusion) and myocytes damage (necrosis enzymes release, immunoperoxidase
      labeling anti-LDH antibody) were evaluated. After ischemia in groups B and C a
      significant reduction of functional alterations and myocytes damage was observed
      with respect to Group A associated with a significant reduction of reperfusion
      edema (heart weight: Group A +29 +/- 3.5%, Group B +15 +/- 3.8%, Group C 16 +/-
      5%, Group D 27 +/- 5%, Group E 33 +/- 4%). At reperfusion time, a significant
      proarrhythmic effect occurred only in groups D and E. A significant reduction of
      postischemic endothelial FITC-albumin diffusion was also observed in groups B and
      C (FITC-albumin diffusion, Group A 32.8 +/- 6% area, Group B 16.33 +/- 5% area,
      Group C 21.7 +/- 4.5% area, Group D 30 +/- 5% area, Group E 35 +/- 7% area). Our
      data show that, in isolated working rat heart, the dopaminergic stimulation with
      low-doses epinine may exert a cardioprotective effect against ischemia
      reperfusion damage by modulating endothelial permeability changes and improving
      coronary microcirculation. The importance of dopaminergic receptors is also
      suggested by the evidence that at higher doses, when alpha and beta-adrenoceptors
      stimulation occurs, this cardioprotective effect is significantly reduced or
      lost.

PMID- 9534311
TI  - [Doppler echocardiographic study of left ventricular function in patients with
      systemic lupus erythematosus].
AB  - This study was aimed at investigating abnormalities in left ventricular size and
      function in patients with systemic lupus erythematosus without overt
      cardiovascular manifestations, in order to detect a very early impairment in
      myocardial function. Seventeen females and 1 male with systemic lupus
      erythematosus of 4 to 20 year duration and without clinical evidence of heart
      disease were studied. Twelve healthy volunteers, matched for age, sex and
      quatelet index, were utilized as controls. Each patient had a two-dimensional M
      mode echocardiographic and Doppler examination. In patients with systemic lupus
      erythematosus there was an increase in left ventricular ejection fraction (p <
      0.001), a slight reduction of end-diastolic volume index and a significant
      decrease of end-systolic volume index (p < 0.001). In the same patients we also
      found prolongation of the isovolumic relaxation time (p < 0.02), a clear
      impairment of diastolic filling parameters. Peak E velocity was lower (p < 0.01),
      peak A velocity was higher (p < 0.01), with a clear lowering, of the
      corresponding E/A ratio (p < 0.001) in patients with systemic lupus
      erythematosus.

PMID- 9534312
TI  - Cor triatriatum associated with degenerative aortic insufficiency in an adult
      patient.
AB  - Cor triatriatum is a rare cardiac anomaly which can be congenital or acquired in
      origin. Congenital cor triatriatum is due to an alteration of the common
      pulmonary vein resorption and therefore the left atrium is divided into two
      chambers, a proximal one, in communication with the pulmonary veins, and a distal
      one, in communication with the mitral valve orifice. The diagnosis is usually
      made at birth, but in rare cases, when the communication between the two chambers
      is wide and the patient is asymptomatic, the lesions may be diagnosed
      incidentally during a routine echocardiographic examination. We report a 32-year
      old man, admitted to our hospital with a diagnosis of aortic insufficiency, in
      whom echocardiography revealed the presence of cor triatriatum. The patient
      underwent aortic valve replacement and resection of the atrial membrane.
      Histology of the aortic valve revealed myxoid degeneration of the spongiosa.

PMID- 9534313
TI  - [Lipidology].

PMID- 9534314
TI  - [Verapamil in myocardial infarct].

PMID- 9534316
TI  - [Aging and endothelial function].

PMID- 9534315
TI  - Endothelial function in coronary artery disease.

PMID- 9534317
TI  - [Calcium channels: multiplicity, function and origin].

PMID- 9534318
TI  - Depression and coronary heart disease.

PMID- 9534319
TI  - Mean-term calcium heparin treatment in acute transmural anterior myocardial
      infarction: effects on left ventricular thrombosis and its complications.
AB  - In order to assess the efficacy of 3-month subcutaneous treatment with calcium
      heparin 12,500 IU twice daily in preventing left ventricular thrombosis and its
      complications a prospective, controlled, randomized trial was carried out in 204
      patients with acute anterior myocardial infarction consecutively enrolled in
      seven Italian hospitals. Left ventricular thrombosis was diagnosed by means of
      two-dimensional echocardiography performed at baseline, after 10 and 90 days of
      treatment. The incidence of thrombosis at the baseline echocardiogram was not
      significantly different between the treatment and control groups, whereas a
      significantly lower incidence of thrombi was observed in treated than in control
      group both on day 10 (3/86, 3.5% and 13/85, 15.3%, respectively; p < 0.05) and
      day 90 (1/65, 1.5% and 6/57, 10.5%, respectively; p < 0.05). The total incidence
      of thrombi after 3 months of therapy was significantly lower in calcium heparin
      treated patients (19/106, 17.9%) than in controls (31/98, 31.6%; p < 0.05). The
      incidence of cardiac events (death, reinfarction, angina) in the two groups
      during the 3-month treatment period was not significantly different. Two embolic
      events, one cerebral and one pulmonary, occurred in the control group, both after
      day 10 of treatment.

PMID- 9534320
TI  - [Female sex is not an independent risk factor in mortality during myocardial
      revascularization].
AB  - To assess if female sex is an independent risk factor for perioperatory mortality
      and morbidity, we have evaluated 971 consecutive patients (16% women) undergoing
      coronary artery bypass graft surgery at the Cardiovascular Disease Institution of
      the University of Turin from 1988 to 1990. In this study at baseline women were
      older and more likely to have diabetes, lower ventricular score and body surface
      area than men. As compared to men, women underwent surgery with delay: the
      surgical mortality rate and prevalence of arrhythmias were higher, and the size
      of the left anterior descending was smaller. At univariate analysis perioperative
      risk factors were as follows: age, diabetes, clinical instability, low body
      surface area, perioperatory infarction, postoperative infections, extracorporeal
      circulation time and left coronary size. At multivariate analysis only diabetes,
      left ventricular score, left anterior descending coronary size and emergency
      surgery were independent risk factors while sex, age and body surface area were
      not predictors of perioperatory mortality and morbidity. It is concluded that
      gender is not the cause of worse outcome in women.

PMID- 9534321
TI  - [Dynamics of post-infarction blood lipids].
AB  - During 1993-1994, 3590 patients who recovered from acute myocardial (undergone 1
      to 6 years earlier) were examined by 139 ambulatory cardiologists. Aim of the
      study was to investigate blood lipid changes in 2435 (67.82%) patients in whom
      total-HDL-and LDL-cholesterol and triglycerides were obtained. These lipids were
      not abnormally elevated and actually very similar to (or slightly lower than)
      those of the general population examined in Italy in the context of the RIsk
      Factors and Life Expectancy Pooling Project (including 70,000 individuals).
      However, blood lipids were, in general, higher in women than in men and declined
      as age increased (unless HDL-cholesterol which tended to increase). Among
      postinfarction patients lipid-lowering drugs were taken by 19% of men and 14% of
      women, which contrasts with proportions observed in the general population (5 and
      4%, respectively). Mean blood lipid values were higher among those who were
      treated with lipid-lowering drugs, either from the postinfarction series or the
      general population (unless HDL-cholesterol which had an opposite trend). These
      data may indicate why treatment was undertaken, although no conclusion may be
      drawn about drug-efficacy. Postinfarction patients examined after 1-2 years from
      illness showed lower values of mean blood lipids than those examined 3-6 years
      after the acute episode (however, the opposite was true for HDL-cholesterol).
      There are several possible explanations for these observations: high lethality in
      infarction-patients with high blood lipids, efficacy of lipid-lowering drugs,
      diet or metabolic changes following acute myocardial infarction. Nevertheless,
      the proportion of postinfarction patients treated with lipid-lowering drugs was
      lower than anticipated from (and/or recommended based on) results of recent
      secondary preventive trials. It seems necessary to repeat (possibly periodically)
      this investigation in large samples of postinfarction patients to assess whether
      and how, in clinical practice, indications are applied from recent large trials
      on secondary prevention of ischemic heart disease.

PMID- 9534322
TI  - [Immediate and long-term results of treatment of focal lesions with aortocoronary
      venous bypass with a stent implant].
AB  - 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. Aim of the
      present study was to determine the in-hospital and long-term results of stent
      deployment in focal, de novo lesions of vein grafts. Thirty-five focal, de novo
      lesions of vein grafts in 31 patients were treated with stent deployment. Twenty
      four patients (77%) had three vessels, 6 (20%) two vessels and 1 (3%) single
      vessel disease. Saphenous vein grafts aged 9.7 +/- 4.2 years (range 1-19 years).
      Twenty-two lesions (63%) were located within the body of the saphenous graft, 8
      (23%) at the graft/coronary artery anastomosis and 5 (14%) at the aorta/graft
      anastomosis. The indications for stent deployment included: suboptimal result
      from balloon angioplasty (defined as > or = 50% post-angioplasty residual
      stenosis) in 29/35 lesions (83%); post-angioplasty coronary dissection with
      threatening occlusion in 4/35 (11%); abrupt closure in 2/35 (6%). Patients were
      screened for death, myocardial infarction, bypass surgery and repeat angioplasty
      during in-hospital stay and after a follow-up of 12 +/- 8 months. Even-free
      survival curve was constructed by the Kaplan-Meier method. Stent deployment was
      successful in all patients. One stent was deployed in 24/35 lesions (69%), half
      Palmaz-Schatz stent in 6/35 (17%) and 2 or more stents in 5/35 (14%). The
      balloon/vessel ratio resulted of 1.0 +/- 0.1 Minimal lumen diameter increased
      from 0.8 +/- 0.4 to 3.8 +/- 0.6 mm, with a mean gain of 1.8 +/- 0.6 mm (range 1.8
      4.0 mm). During the in-hospital period 1 patient (3.2%) died and 1 (3.2%) had a
      non Q wave myocardial infarction. Therefore, the clinical success rate, was 94%.
      During the follow-up period, 2 patients died (6.9%), 2 (6.9%) developed a non Q
      wave myocardial infarction, 1 (3.4%) underwent bypass surgery and 3 (10.3%)
      underwent repeat angioplasty. The estimated 2-year event-free survival rate (free
      from myocardial infarction, repeat surgery and repeat angioplasty) was 62%. In
      conclusion, Palmaz-Schatz stent deployment in focal, de novo vein grafts presents
      a high rate of procedural success, a low rate of acute complications and good
      long-term results.

PMID- 9534323
TI  - [The influence of ACE inhibitors on urinary electrolyte secretion and the
      response to transitory hypovolemia in chronic heart failure].
AB  - Renin-angiotensin system promotes sodium and chloride retention, participates in
      the defense response to hypovolemia and, in congestive heart failure, contributes
      to edema formation and progression of the disease. We investigated whether ACE
      inhibitors interfere with the action of the renin-angiotensin system on the
      nephron, and therefore with water and urinary electrolytes excretion. The
      interaction among renin-angiotensin system, diuretic treatment and urinary
      electrolytes was evaluated both during chronic treatment and in response to acute
      renin-angiotensin system activation as that observed after extracorporeal
      ultrafiltration-induced transient hypovolemia. Plasma renin activity and
      aldosterone, body fluid balance and urinary sodium, chloride and potassium
      concentrations were evaluated in 30 patients with congestive heart failure in
      NYHA II-III functional class, grouped according to whether long-term therapy did
      not include (Group I, n = 15) or included (Group II, n = 18) ACE-inhibitors. All
      parameters were evaluated at baseline and after a single session of
      extracorporeal ultrafiltration. At baseline, urinary output and urinary sodium
      and chloride concentrations were similar in the two groups, while urinary
      potassium concentration was lower in patients assuming ACE-inhibitors (Group II).
      Plasma renin activity was higher and aldosterone was lower in Group II than in
      Group I. After removal of similar amounts of plasma water by extracorporeal
      ultrafiltration, body weight decreased in both groups but the decrease was
      maintained in the following days only in Group II patients. A transient reduction
      (48 hours) of both plasma volume and urinary output was observed after
      ultrafiltration in both groups. Despite plasma renin activity and aldosterone
      increase, urinary electrolytes response to ultrafiltration was different in the
      two groups: sodium and chloride were reduced, and potassium did not change in
      Group 1 while, in Group II, sodium and chloride did not change and potassium
      excretion was significantly increased. In conclusion, chronic treatment with ACE
      inhibitors does not enhance the excretion of sodium in congestive heart failure
      but just mitigates potassium loss. The role of these drugs becomes particularly
      relevant during acute renin-angiotensin system activation due to hypovolemia; in
      this setting ACE-inhibitors counteract sodium and chloride retention resulting in
      a potential hazard due to interference with the defence mechanisms toward
      hypovolemia, and an amplification of extracorporeal ultrafiltration efficacy by
      preventing edema recovery after its mechanical removal.

PMID- 9534325
TI  - [The philosophy of blood and lymph circulation].

PMID- 9534324
TI  - [Two cases of "scombroid syndrome" with severe cardiovascular compromise].
AB  - Two cases of severe intoxication after ingestion of cooked tuna fish were
      observed. Symptoms and clinical signs were consistent with the scombroid
      syndrome. Cardiovascular shock was observed in both patients and was associated
      with subendocardial myocardial infarction in 1 case and acute pulmonary edema
      with myocardial ischemia in the other. The importance of ECG monitoring in the
      Intensive Coronary Care Unit is stressed.

PMID- 9534326
TI  - [Immunology].

PMID- 9534327
TI  - [Lymph node excision in stomach cancer: classifications, presuppositions and our
      experience].

PMID- 9534328
TI  - [Morpho-functional adaptation and motility of the small intestine and colon after
      extensive intestinal exclusions].
AB  - Recent advances in anesthetic and surgical techniques have increased the survival
      of patients after extensive bowel exclusions. This, in addition to the increased
      use of intestinal bypass for the treatment of obesity, has substantially
      increased the number of persons living with a short bowel. Proper management of
      these individuals is based on a thorough understanding of the pathophysiology of
      the shortened gastrointestinal tract.

PMID- 9534329
TI  - [Therapeutic possibilities of surgical treatment of patients with non-small-cell
      lung carcinoma and adrenal metastasis].
AB  - Reports on successful surgical treatment of patients with non-small lung
      carcinoma and adrenal metastasis are infrequent. For this reason the Authors
      believe interesting to report a case of a patient with non-small lung cancer and
      single adrenal metastasis who underwent lung superior lobectomy and, after
      chemotherapy, adrenalectomy. A relapse was observed one year later in the lumbar
      region and the patient was reoperated undergoing removal of the recurrence
      associated to splenectomy and pancreas tail resection; thereafter the patient was
      treated with local radiotherapy. Forty-one months after the first operation the
      patient is well and disease free.

PMID- 9534330
TI  - [Necrotizing fasciitis: apropos of a case].
AB  - Necrotizing fasciitis is an infection which involves soft tissues up to the
      fascia, with wide areas of necrosis, and is mainly caused by group A beta
      hemolytic Streptococcus. The Authors report a case recently observed and after an
      accurate review of the Literature, taking into account the most recent
      pathogenetic knowledges, confirm the necessity of an early diagnosis based on
      clinical criteria but above all on histological biopsy. The treatment is mainly
      surgical, and allows, together with the medical treatment, to subdue the rapid
      progression of the infection which notwithstanding maintains an high mortality
      rate.

PMID- 9534331
TI  - [Retrorectal hamartomatous cysts or "tail gut syndrome": a case report and review
      of the literature].
AB  - Retrorectal cyst hamartomas or so called tail gut syndrome are dystopic lesions,
      rarely reported in Literature, characterized by the presence of cysts lined by
      mucous-producing ciliated epithelium. The Authors report a case, recently
      observed and surgically treated, in a 55 year old male, hospitalized because of
      an abscess and fistula in the right buttock diagnosed to be a cyst hamartoma. The
      Literature is reviewed as well.

PMID- 9534332
TI  - [Peritoneal carcinosis secondary to breast carcinoma].

PMID- 9534333
TI  - [Hemoptysis in a patient with acquired anomaly of the arterial vascularization of
      the lung].
AB  - An anomalous systemic pulmonary supply may be acquired and present only one
      symptom: hemoptysis. The incidence of this pathology is unknown. A case of
      acquired systemic pulmonary arterialization was observed after surgical
      intervention of myocardium vascularization with the left mammary artery. The
      diagnosis was obtained through an arteriography of the left mammary artery. In
      this case, the therapy consists in ablating the affected parenchyma followed by
      the interposition of a bovine pericardium patch between the mammary artery and
      the remaining pulmonary tissue.

PMID- 9534334
TI  - [Pericardial cysts. Report on 9 treated cases].
AB  - From 1976 to 1993, nine patients (5 men, 4 women) with pericardial cysts were
      treated in Authors' Department. Of the nine cysts, six were located in the right
      cardiophrenic angle, one in the subcarinal site, one in the right
      tracheobronchial angle, and one in the para-auricular site just above the
      diaphragm. Four patients were asymptomatic. A correct diagnosis was possible
      preoperatively only in patients with cysts typically located in the cardiophrenic
      angle. Eight patients were surgically treated by a standard posterolateral or
      axillary thoracotomy. One patient with a large pericardial cyst underwent needle
      percutaneous aspiration and CT-guided drainage of the cyst with a positive
      outcome. There was no operative morbidity or mortality.

PMID- 9534335
TI  - [6 years of experience in inguinal and femoral hernioplasty in patients over 65
      years of age].
AB  - From April 1990 to November 1996, 313 inguinal and 14 femoral hernias were
      repaired in 295 subjects with a mean age of 74 years (66 to 97). Concomitant
      diseases increasing the operative risk were present in 206 subjects (70 per
      cent). A mesh repair was performed with "tension-free" or "plug" techniques in
      all but 23 inguinal and 2 femoral herniorrhaphies where the Bassini or the
      Shouldice procedures were adopted. Fifty-two inguinal hernias were recurrent, 11
      emergency herniorrhaphies were performed for strangulation. Almost all operations
      (305), including 9 emergency herniorrhaphies, were carried out under local
      anaesthesia. There was no perioperative mortality. Acute intestinal bleeding
      occurred after surgery in a subject with colon diverticulosis. One urinary
      retention following emergency hernia repair under general anaesthesia and 2
      following elective hernia repair under local anaesthesia in 2 subjects with
      hypertrophy of the prostate were observed. Some episodes of hypotension and/or
      bradycardia were observed either during or after surgery. Local complications
      following inguinal hernioplasty were 5 (1.5%) scrotal hematomas, 3 (0.9%) wound
      infections and 1 case (0.4%) of orchitis with atrophy after repair of a recurrent
      hernia. There were 1 recurrence after Bassini, 1 after Shouldice, and 1 (0.4%)
      after mesh inguinal hernioplasty. Using local anaesthesia and a mesh repair
      elective surgery of inguinal and femoral hernias can be safely and effectively
      performed in elderly patients. Consequently, early elective surgery should be
      recommended to avoid the risk of an emergency operation.

PMID- 9534336
TI  - [Riedel's thyroiditis: a case report and review of the literature].
AB  - Riedel's thyroiditis is a very rare disease of unknown aetiology, occasionally
      associated with retroperitoneal and mediastinal fibrosis. It is a benign
      condition, but may be confused with an anaplastic carcinoma of the thyroid. The
      differential diagnosis with anaplastic carcinoma is assured only by
      intraoperative biopsy. The Authors report a clinical case: symptoms were a
      progressive enlargement of the thyroid gland, left recurrential palsy, dyspnoea
      and dysphagia. The surgical treatment was total thyroidectomy, performed with
      bilateral neurolysis of recurrent nerves. The patient was also under adjuvant
      corticosteroid treatment.

PMID- 9534337
TI  - [Our experience in the percutaneous treatment of varicocele].
AB  - For its high incidence among young men and its affecting male fertility,
      varicocele requires an accurate screening, as well as an early and definitive
      treatment. The Authors report their experience in the treatment of varicocele
      with sclerotherapy: 24 patients underwent sclerotherapy of the left internal
      spermatic vein with a success rate of 91%. Complications never required
      hospitalization or surgery. Percutaneous therapy represents thus the treatment of
      choice in case of varicocele: compared with surgery, it offers similar clinical
      results and a lower recurrence rate, and it can be performed on an outpatient
      basis. Surgery should be performed only when anatomic variants make percutaneous
      treatment not feasible.

PMID- 9534338
TI  - [Level of immunosuppressive acidic protein in the fluid of breast cysts].
AB  - IAP marker was detected by radio-immunodiffusion in breast gross cyst fluid and
      in serum. No correlation was found between this antigen and cyst' cytological
      type, serum concentrations and acute phlogosis. In most cysts IAP was not
      valuable; on the other hand, high levels of glycoprotein were found only in the
      subgroup on relapsed class of apocrine cysts.

PMID- 9534339
TI  - [Laboratory diagnosis of cytomegalovirus infections].

PMID- 9534340
TI  - [Usefulness of urine and blood cultures for diagnosing cytomegalovirus infection
      in the kidney transplant recipient].
AB  - OBJECTIVE: To prospectively and comparatively study the usefulness of urine
      (viruria) and blood (antigenemia pp65 and culture) (viremia) for the diagnosis of
      cytomegalovirus (CMV) infection in renal transplant (RT) recipients. MATERIAL AND
      METHODS: All RT recipients at our hospital were studied from January 1995 to
      December 1996. After decontamination, urine specimens were inoculated into two
      MRC-5 cell line vials. Polymorphonuclear cells were extracted from peripheral
      blood by sedimentation in saline dextran and were used for antigenemia pp65 test
      and for culture in shell-vial. RESULTS: A total of 1,335 specimens from 43
      patients were studied. CMV was recovered from 110 out of the 913 (12%) urine
      specimens and from 101 out of the 422 (23.9%) blood specimens (antigenemia and/or
      viremia). CMV detection was first obtained by a positive blood test in 23
      patients (88.4%), whereas the urine specimen was the first positive test in only
      three (11.6%) patients (p = 0.0001). A positive result in blood preceded a
      positive result in urine by a mean of 10.3 days (range: 2-73 days). Antigenemia
      and viremia were simultaneously positive in 61.5% of patients. In three patients
      a positive antigenemia preceded viremia by 14 days. In seven patients (26.9%)
      only the shell-vial culture was positive. Culture preceded antigenemia by a mean
      of 7.6 days. In the 26 patients, the time elapsed until the first positive blood
      specimen for CMV was 37.3 days (range: 11-88 days). CONCLUSION: According to the
      results obtained we believe that blood (antigenemia pp65 and/or viremia) should
      be considered as the only really useful specimen for the diagnosis of
      infection/disease caused by CMV in RT recipients. The urine specimen lacks a
      diagnostic and clinical usefulness and therefore should not be used in these
      patients.

PMID- 9534341
TI  - [Bacteremia in the elderly: associated and prognostic factors].
AB  - BACKGROUND: Bacteremia is associated with high morbidity and mortality rates and
      its prevalence increases with age. The objective of the present investigation was
      to know the epidemiology, associated factors and prognosis in patients with
      bacteremia in our environment and in relation with age. METHODS: Two hundred and
      twenty-nine episodes of bacteremia were prospectively studied; 97 (42%) cases
      corresponded to patients aged > 70 years. The prognostic factors were evaluated
      by the univariate and multivariate analysis in the whole cohort and univariate
      study of associated factors for an age > 70 years. RESULTS: The etiology,
      infectious sources, nosocomial acquisition, and complications apart from shock (p
      = 0.02) were similar in the elderly patients. The associations of diabetes (p =
      0.05), COPD and/or heart disease (p = 0.01), and exitus were higher for patients
      > 70 years. The main independent prognostic factor in the series was disseminated
      intravascular coagulation (p < 0.001, multivariate OR 14.2). CONCLUSIONS:
      Patients older than 70 years have a higher incidence of shock and mortality
      associated with infection. The higher overall mortality rate in the series was
      associated with disseminated intravascular coagulation and multisystemic failure
      irrespective of age.

PMID- 9534342
TI  - [Validation of the Alcohol Use Disorders Identification Test (AUDIT) in primary
      care].
AB  - The results of the validation for the AUDIT (Alcohol Use Disorders Identification
      Test) in Primary Care are here reported. A total of 326 patients who attended two
      primary care centers were interviewed. In a first interview they answered the
      AUDIT questions and later were classified on the basis of disturbances caused by
      alcohol use: abuse or dependency. The diagnosis of abuse or dependency was
      obtained with the structured interview for DSM-III-R. Reliability was determined
      by the test-retest correlation and internal consistency by Cronbach's alpha
      coefficient. Efficacy was calculated by means of the area under the curve
      (receiver operating characteristics). A quarter of the interviewed patients were
      diagnosed of some disturbance caused by alcohol use. The internal reliability of
      the test was acceptable (Cronbach's alpha coefficient 0.86). The test-retest
      correlation coefficient was 0.90. All the questions acceptably correlated with
      the total in the scale. A cut-off point of 8 was the most efficient for the whole
      sample (90% sensitivity and 90% specificity). For females, the most efficient cut
      off point was 6. For patients aged over 60 years, the most efficient cut-off
      point was 5 for both sexes. This study confirms the usefulness of AUDIT for
      screening alcohol-related problems in Primary Care.

PMID- 9534343
TI  - [Estimating the angiographic risk from isotopic ventriculography in ischemic
      heart disease].
AB  - The objective of this study was to determine the diagnostic accuracy of the
      ejection fraction (EF) measurement, calculated by isotopic ventriculography, to
      predict the angiographic risk in a group of patients with previous acute
      myocardial infarction and significant segmentary disturbance of wall motility. A
      total of 125 patients were studied (100 males and 25 females, aged 23 to 78
      years). Isotopic EF showed positive and negative predictive values of 85% and
      93.3%, respectively, for the low risk group. The corresponding values for the
      moderate risk group (angiographic EF from 31% to 54%) were 80.3% and 79.6%. And
      for the high risk group (angiographic EF < 31%) 89.4% and 83%. In conclusion,
      from the present work we state that with a high probability isotopic EF places
      each patient in his/her corresponding high, moderate, or low angiographic
      (biological) risk.

PMID- 9534344
TI  - [Reversible hypophyseal disfunction and hyperplasia in two cases of primary
      hypothyroidism].
AB  - BACKGROUND: Some patients with primary hypothyroidism (HP) develop massive
      thyrotrope cell hyperplasia determining pituitary hyperplasia with suprasellar
      enlargement and pituitary dysfunction. Although TRH secretion undoubtedly has
      some influence, the intervention of other possible factors determining this
      hyperplasia and dysfunction has been little assessed. PATIENTS AND METHODS: Two
      patients with primary hypothyroidism with a serum TSH > 1,000 mU/I were studied.
      By means of CT and MR a pituitary hyperplasia was ascertained in the two
      patients. The pituitary functional reserve was investigated by the serum response
      of TSH and prolactin to the administration of TRH (400 micrograms, i.v.),
      bromocriptine (BRC, 5 mg, oral route), somatostatine (ST, 50 micrograms/kg/min,
      i.v. perfusion), and gonadotropin releasing hormone (GnRH, 100 micrograms, i.v.).
      RESULTS: The TRH induced increment of TSH was 145% and 193%, respectively,
      compared with basal values. After the administration of BRC, TSH decreased to 57%
      and 84% of basal values, and PRL to 46% and 43%, respectively. TSH and PRL
      concentrations did not change after the administration of ST or GnRH. In both
      cases, hyperplasia and pituitary dysfunction returned to normality after
      substitutive therapy with levothyroxine. CONCLUSIONS: Basal hyperprolactinemia
      and TSH and PRL responses to BRC administration suggest that central dopaminergic
      activity is decreased or abolished in patients with HP and pituitary hyperplasia.
      The massive thryrotrope cell hyperplasia and hypothyroidism itself determine
      pituitary dysfunction, which reverts after therapy with levothyroxine, a fact
      which is scarcely documented in literature.

PMID- 9534345
TI  - [Familial outbreaks of fascioliasis: usefulness of serologic investigation by
      enzyme immunoassay].
AB  - BACKGROUND: To assess the usefulness of an enzyme immuno-assay test for the
      diagnosis of two familial outbreaks of Fasciola hepatica parasitosis in the
      Zamora area, where watercress are a normal part of the diet. PATIENTS AND
      METHODS: The microbiological diagnosis of two familial outbreaks of fascioliasis
      was analyzed, which included the search for eggs in feces by the Kato technique
      and two serologic tests, one screening test by indirect hemagglutination, and a
      confirmatory test by enzyme-immunoassay in 12 patients. RESULTS: Five out of the
      six seropositive patients had eggs detected in their feces. To note that two of
      the patients with eosinophilia that excreted eggs--one asymptomatic and the other
      with abdominal pain--had a positive result in the EIA test only and with high
      titers. CONCLUSIONS: The EIA test is useful for the diagnosis and study of
      fascioliasis outbreaks to interpret the significance of low titers in the
      screening test in patients with eosinophilia.

PMID- 9534346
TI  - [Management of solitary pulmonary nodule].

PMID- 9534347
TI  - [A 74 year-old male with progressive asthenia and purpuric lesions].

PMID- 9534348
TI  - [Hepatomegaly and asthenia].

PMID- 9534349
TI  - [Traumatic disseminated pneumoencephalus].

PMID- 9534350
TI  - [Macrocreatine kinase in errors of CK-MB determination].

PMID- 9534351
TI  - [Unusual case of biclonal gammopathy of undetermined significance].

PMID- 9534352
TI  - [Lepra presenting as bilateral facial palsy].

PMID- 9534353
TI  - [Pneumocystis carinii pneumonia in HIV primary infection].

PMID- 9534354
TI  - [Transplantation of hepatocytes: myth of reality].

PMID- 9534355
TI  - Effect of pancreatic islets on splenic hepatocellular transplantation.
AB  - PURPOSE OF THE STUDY: To determine whether Langerhans' islets exert a beneficial
      effect on splenic hepatocellular transplantation. HYPOTHESIS: the addition of
      pancreatic islets to hepatocytes would improve their normal function through the
      support of insulin and glucagon in the same proportions as they usually receive
      in the hepatic environment. EXPERIMENTAL DESIGN: Potential improvement in the
      hepatocellular function to be evaluated by means of regenerative activity
      recorded after applying a specific stimulus (partial hepatectomy and/or
      cyclosporine A). METHODS: An immunohistochemical technique (antinuslin
      antibodies) was used to confirm the presence of active islets of Langerhans in
      the spleen. Microcytophotometry was used to quantify hepatocyte regeneration.
      RESULTS: Although demonstrating the presence of active (insulin-positive) islets
      together with hepatocytes in the spleen was feasible, the expected positive
      influence on the regenerative activity of hepatocytes was impossible to prove.
      CONCLUSIONS: Further study is needed to reach definitive conclusions about the
      real usefulness of pancreatic islets in hepatocyte transplantation.

PMID- 9534356
TI  - Highly selective laparoscopic vagotomy in the management of duodenal ulcer and
      gastroesophageal reflux: the technique and results in 150 patients.
AB  - Highly selective vagotomy is the surgical treatment of choice for duodenal ulcer.
      It is the procedure that best maintains digestive anatomy and physiology with
      very few side effects, and widely performed all over the world. It has also been
      employed to treat gastroesophageal reflux for its many advantages: it reduces
      gastric acid output; it permits easy access to the gastroesophageal junction,
      assuring a precise, secure fundoplication. We have been using this technique in
      open surgery since 1978. This prospective study reproduces with laparoscopic
      guidance, the same technique we used to employ in open surgery. The purpose is to
      analyze the laparoscopic procedure and discuss the results in 150 patients who
      were treated between March 1992 and August 1996. This series deals with 36
      patients with duodenal ulcer, 80 with gastroesophageal reflux and 34 who
      presented both. All the duodenal ulcer patients were treated successfully, with
      no recurrences to date. Recurrences have been recorded in two complex cases of
      gastroesophageal reflux. The remaining patients show no clinical evidence of
      reflux and present normal endoscopic findings, esophageal manometric studies and
      24-hour esophageal pH measurements. Laparoscopic surgery with this technique
      appears to be an interesting alternative to prolonged medical treatment of these
      diseases in certain refractory patients.

PMID- 9534358
TI  - Acute pancreatitis and microcrystals. Importance of the bile collection and
      biochemical parameters.
AB  - For a substantial number of patients with acute pancreatitis, no recognizable
      causes can be identified and such cases are called "idiopathic". With the
      introduction of duodenal bile collection for microscopic examination, it became
      possible to detect minor constituents of the bile, such as cholesterol and/or
      calcium bilirrubinate crystals. The mechanism by which crystals produce
      pancreatitis seems to be related to migration of aggregate crystals through the
      papilla, inducing papillary trauma or temporary impaction which can cause a
      biliopancreatic reflux. We now report a series of 45 patients with acute
      pancreatitis idiopathic, 120 with gallstones and 22 alcoholic. Of the patients
      with idiopathic pancreatitis whom we studied by biliary drainages, 22 were found
      to have abnormal drainages (MC+) (20 cholesterol crystals and 2 calcium
      bilirrubinate), 9 patients had more than 10 crystals per slide. The microcrystals
      positive (MC+) group had significantly higher values for AST (69.8 +/- 1.7) (mean
      +/- SEM), ALT (123.3 +/- 28.1), FA (252 +/- 28.1), G-GT (144.6 +/- 26.7) and BT
      (1.83 +/- 0.37) than the microcrystals negative group: AST (19.6 +/- 2.5), ALT
      (28.3 +/- 5.8), FA (170.5 +/- 15.1), G-GT (54.3 +/- 10.7) and BT (0.76 +/- 0.09).
      The more 10 crystals group had higher values (AST: 82.0 +/- 29.1, ALT: 143.1 +/-
      43.5, FA: 294.8 +/- 57.2, G-GT: 171.8 +/- 38.4, BT: 2.61 +/- 0.82) than in the
      microcrystals negative group. We concluded that in the absence of other overt
      causes, the presence of crystals in bile of patients with pancreatitis justifies
      etiology. The number is not important.

PMID- 9534357
TI  - Anastomotic stricture with the EEA-Stapler after colorectal anastomosis.
AB  - OBJECTIVE: Analysis of colorectal anastomosis stricture incidence after anterior
      resection of the rectum performed with the EEA-Stapler. To find out if
      differences existed in stricture incidence considering factors such, as age,
      neoplasia, postoperative radiotherapy, tumor stage and anastomic level. DESIGN:
      Longitudinal descriptive study. PATIENTS AND METHOD: 67 patients who underwent
      rectal anterior resection using the EEA-Stapler were evaluated. Data from sex,
      age, indication for operation, postoperative radiotherapy, tumor staging and
      anastomic level were recorded and compared with presence of stricture
      anastomosis. Stenosis was evaluated and graded as follows: grade O, no stenosis;
      grade I, no symptoms, X-ray or endoscopic finding; grade II, symptoms, the
      patients require ballon catheter dilation; and grade III, invalidant symptoms,
      the patients require surgery. RESULTS: Twelve patients (20%) were recorded as
      grade II and 3 patients (5%) as grade III. There were no statistically
      significant differences between prevalence of stricture and sex, age, neoplasic
      or non-neoplasic conditions, previous radiotherapy, level of anastomosis, and
      tumor stage. CONCLUSION: Stenosis after colorectal anastomosis with stapler
      devices must not be considered as an uncommon complication. In 20% of patients it
      may be a serious state that may require repeated catheter balloon dilations or
      surgery. Such condition is not dependent on diverse factors studied.

PMID- 9534359
TI  - [Bleeding varix in the ileum of a cirrhotic patient].

PMID- 9534360
TI  - [Ogilvie's syndrome: 10 observations. Diagnostic and therapeutic aspects].

PMID- 9534361
TI  - [Indirect hyperbilirubinemia secondary to Epstein-Barr viral hepatitis].

PMID- 9534362
TI  - [Retrorectal hamartoma].

PMID- 9534363
TI  - Air abrasion: the future of restorative microdentistry.

PMID- 9534364
TI  - Root caries in vitro after low fluence argon laser and fluoride treatment.
AB  - Because the numbers of dentate elderly are increasing, root caries prevention has
      become a great concern to the dental profession. This in vitro study evaluates
      the influence of combining low fluence argon laser treatment and acidulated
      phosphate fluoride treatment on caries initiation and progression in human root
      surfaces. The combination of low energy laser treatment and fluoride treatment
      increased the caries resistance of root surfaces when compared with no treatment
      and with laser irradiation treatment alone.

PMID- 9534365
TI  - Legionella and human disease: Part 1: A path of scientific and community
      discovery.

PMID- 9534366
TI  - Management of ectopic eruption of permanent molars.
AB  - Ectopic eruption can be defined as a tooth erupting in an abnormal position or
      orientation. The maxillary first permanent molar is the most commonly affected
      tooth. Correction of ectopically erupting permanent molars is critical for the
      development of a stable occlusion and is an important component of interceptive
      orthodontic treatment. The clinician can choose from a variety of effective
      treatment modalities to successfully manage ectopically erupting permanent
      molars.

PMID- 9534367
TI  - Effects of toothbrush design and brushing proficiency on plaque removal.
AB  - A single-blind, short-term cross-over clinical trial compared the plaque removal
      performance of three commercially available manual toothbrushes. A sample of 25
      dental hygiene students, 19 to 42 years old, served as participants. On 3
      separate occasions, participants were instructed to refrain from toothbrushing or
      flossing for 24 hours before clinical trials. A prebrushing plaque index using
      disclosing solution was performed on each participant. One of the 3 test brushes
      was then randomly dispensed to each participant, and they were allowed to brush
      for 90 seconds without the aid of a mirror. A postbrushing plaque index was then
      performed on each participant. This procedure was repeated 2 more times at 2-week
      intervals so that each participant was tested with all 3 toothbrushes. Previous
      studies of this kind using random participant samples have suggested that brush
      design does indeed affect the efficacy of plaque removal. This study used
      participants who were well versed on efficient toothbrushing technique to
      determine if improved brushing skills would overshadow advantages in toothbrush
      design. No significant differences in performance were detected between the test
      brushes for any of the three scored areas.

PMID- 9534368
TI  - Clinical considerations in the management of orbital blow-out fractures.
AB  - The management of orbital blow-out fractures has long been controversial. There
      are primarily two methods of treatment. One is a conservative approach that
      delays any kind of initial surgical intervention on the basis that most
      situations attributable to blow-out fractures resolve over time, obviating the
      need for surgery. On the other hand, initial aggressive surgical repair of blow
      out fracture injuries is much more successful than secondary reconstructive
      procedures. This article discusses the advantages and disadvantages of both
      treatment methods.

PMID- 9534369
TI  - Single- and multisurface restorations.

PMID- 9534370
TI  - Dentistry in the operating room.
AB  - Some special patients are unable to tolerate dental care in outpatient dental
      offices. Providing dental care under general anesthesia in an operating room
      setting involves various medical, dental, and hospital issues and procedures that
      differ from outpatient care. This article reviews pertinent information for the
      dental management of patients who require general anesthesia.

PMID- 9534371
TI  - Rational predictable posthole preparation.
AB  - Restoration of the endodontically treated tooth is a common occurrence in
      everyday dental practice. Unfortunately, clinical posthole preparation seems to
      be a random technique. Even for a prefabricated post supplied with matching
      drills, the task is often difficult or not straightforward. Some questions
      inevitably arise. How long should the posthole be? How wide should the canal be
      prepared? How can the proper width be maintained so that the prefabricated post
      does not strip in the canal and lose its retention? If it is decided to use a
      cast post, what is the best posthole preparation to maximize retention? Is there
      an easy way to avoid perforating the root while preparing the canal for the post?
      Clinically, how can the posthole be prepared quickly, easily, and predictably
      every time? These key questions must be addressed when preparing the posthole.

PMID- 9534372
TI  - The issues of practice management, as seen through Dr. Deming's glasses.

PMID- 9534373
TI  - How to profit from.... endodontics. Getting paid when the treatment is an
      emergency.

PMID- 9534374
TI  - How to profit from.... endodontics. A system for endodontic emergencies.

PMID- 9534375
TI  - How to profit from.... endodontics. Advances enhance treatment options.

PMID- 9534376
TI  - Salary packages.

PMID- 9534377
TI  - A time to share good ideas.

PMID- 9534378
TI  - Working alongside the buyer.

PMID- 9534379
TI  - What is doctor/patient privilege?

PMID- 9534380
TI  - An oral surgeon's perspective on patients' vulnerability.

PMID- 9534381
TI  - Cast emotion aside and consider managed care differently.

PMID- 9534382
TI  - The 'show me' practice.

PMID- 9534383
TI  - Dentists of distinction.

PMID- 9534384
TI  - How to profit from ... the Internet. Nothing but the 'net'.

PMID- 9534386
TI  - How to profit from ... the Internet. As handy as a Swiss Army knife.

PMID- 9534385
TI  - How to profit from ... the Internet. Like a 'daily electronic study club'.

PMID- 9534387
TI  - How to profit from ... the Internet. The web of dentistry.

PMID- 9534388
TI  - Practice transitions.

PMID- 9534389
TI  - Are you building relationships or manufacturing units of dentistry?

PMID- 9534390
TI  - How to profit from .... practice analysis. Survey examines trends in collections.

PMID- 9534391
TI  - How to profit from .... practice analysis. How to analyze your practice by the
      numbers.

PMID- 9534392
TI  - How to profit from .... practice analysis. A flat practice is a declining
      practice.

PMID- 9534393
TI  - Dentistry joins a global pursuit for quality.

PMID- 9534394
TI  - A long fuse would be nice.

PMID- 9534395
TI  - Sidestepping Caller ID.

PMID- 9534396
TI  - The freedom to practice 'wherever'.

PMID- 9534397
TI  - When the owner stays on....

PMID- 9534398
TI  - How to profit from ... implants. From the pioneers, five lessons learned.

PMID- 9534399
TI  - How to profit from ... implants. Reviving services in managed care era.

PMID- 9534400
TI  - How to profit from ... implants. Integrate implants into daily practice.

PMID- 9534401
TI  - How to profit from ... implants. Establishing implant fees.

PMID- 9534402
TI  - How to profit from ... implants. Working with insurers for reimbursement.

PMID- 9534403
TI  - Hogging the mike.

PMID- 9534404
TI  - Staying compatible--after the deal.

PMID- 9534405
TI  - 'Independent practitioners' answer only to the patient.

PMID- 9534406
TI  - Does value equal productivity?

PMID- 9534407
TI  - Adverse effects of dental local anaesthesia.
AB  - This paper considers the adverse effects that a patient may suffer as a result of
      anticipating an injection of dental local anaesthetic. Although most of these are
      extremely rare (a testimony to good technique), the dental practitioner should be
      aware of the possibility of their occurrence and of ways to deal with them.

PMID- 9534408
TI  - Surgical uprighting of an impacted mandibular second molar.
AB  - This case reports the surgical management of an impacted lower second molar. It
      also highlights other treatment options available when orthodontic treatment is
      contraindicated.

PMID- 9534409
TI  - The use of silicone dentures for edentulous patients.
AB  - There are a number of occasions when a soft denture base will be of much more
      benefit to an edentulous patient than a conventional rigid prosthesis. This
      article discusses three such cases.

PMID- 9534410
TI  - Influences of smoking on the periodontium and dental implants.
AB  - The purpose of this article is to review current information on the role of
      smoking in destructive periodontal disease and in increasing the likelihood of
      failure of endosseous dental implants. Practical recommendations are made on the
      role of the dental health professional in everyday dealings with patients who
      smoke.

PMID- 9534411
TI  - Advanced surgical procedures: bone augmentation.
AB  - Over the last ten years there has been a significant increase in the range and
      type of edentulous defects that can be treated using osseointegrated implants.
      Encouraged by the long-term success of implant reconstructions in the edentulous
      mandible and maxilla, and the availability of novel implant attachments,
      clinicians will now undertake more elaborate treatment involving the partially
      edentate and those with localized or generalized tissue deficiencies. This
      clinical trend places increasing demands on the predictability, complexity and
      accuracy of the surgical procedure necessary to allow a successful prosthetic
      reconstruction. This is especially so when potential implant sites lie in areas
      of high aesthetic or functional requirements.

PMID- 9534412
TI  - How to do it: making audit work.
AB  - The orthodontic Audit Working Party of the Faculty of Dental Surgery, Royal
      College of Surgeons of England, in collaboration with the Centre for Medical
      Education, Ninewells Hospital and Medical School, Dundee developed an audit
      project entitled 'Clinical Audit: Scenarios for Evaluation and Study'. The aim of
      the project was to contribute to the construction of clinical guidelines for
      orthodontists. This article, the first of a short series, describes the
      background to and general results of the study. Further articles will study
      individual aspects of the project.

PMID- 9534413
TI  - Early treatment of Class III malocclusion? Colin's case.
AB  - This is the first of six simulated case reports accompanying the questionnaire
      detailed in the article 'How to Do It: Making Clinical Audit Work' found earlier
      in this issue. You will find comprehensive discussion of the problem of making a
      decision about the early treatment of Class III malocclusion.

PMID- 9534414
TI  - The status of restorative dental materials.
AB  - The ideal restorative material should enable teeth which have suffered trauma or
      have been damaged during the removal of caries, to be restored to their original
      function and appearance. At the same time a seal should develop between the
      material and the tooth such that bacteria-laden fluids cannot permeate the
      dentine and reach the pulp. Few, if any, of the materials currently available
      fulfil these requirements. This short series will consider the current status of
      each.

PMID- 9534415
TI  - The aesthetic management of severe dental fluorosis in the young patient.
AB  - The prevalence of dental fluorosis appears to be on the increase. Although in its
      mild form the condition is not considered to be of cosmetic significance, the
      more severe forms can cause great psychological distress to the affected
      individual. This article discusses the prevalence and mechanisms of dental
      fluorosis, and the aesthetic management of severe fluorosis in the young patient.

PMID- 9534416
TI  - Surgical emphysema following dental treatment: two cases.
AB  - Surgical emphysema is an uncommon complication of dental treatment despite the
      frequent use of air-driven handpieces and high-speed water-cooled equipment in
      dental practice. As a consequence it may either go unrecognized or be
      misdiagnosed. Although most cases resolve spontaneously, some patients require
      emergency intervention. This article outlines the condition and its management
      and describes two cases that arose during routine dental treatment.

PMID- 9534417
TI  - Design, maintenance and biomechanical considerations in implant placement.
AB  - Successful treatment using implants involves careful consideration of fixture
      placement and prosthesis design if the biomechanical conditions are to be
      optimized. These parameters may be related to the implant/tissue interface at the
      individual fixture level, and thence to the relationship between the components
      of a prosthesis. The influence of the nature and magnitude of occlusal forces can
      also be significant and should be carefully assessed before placement.

PMID- 9534418
TI  - Topical use of miconazole antifungal oral gel on warfarinized patients: a word of
      caution.
AB  - Oral candidosis is common, particularly in elderly patients who wear dentures.
      Many of these patients also have systemic diseases, including conditions for
      which they have to take oral anticoagulants, most commonly warfarin. Although the
      effect of parenterally administered miconazole on anticoagulant control is well
      known, the fact that small amounts of topically applied miconazole oral gel can
      have a similar effect is poorly recognized.

PMID- 9534419
TI  - An extraction dilemma: Cheryl's case.
AB  - This article describes treatment options for a teenager with a mild, although
      aesthetically unpleasing, malocclusion. The opinions of British orthodontists, as
      obtained through the CASES project, are summarized and the patient's actual
      treatment is discussed.

PMID- 9534420
TI  - Management of the short clinical crown by indirect restorations.
AB  - This paper describes the acute and chronic causes of short clinical crowns and
      their management. Fracture or trauma are common causes of acute failures whilst
      toothwear is the most common cause for chronic causes. There are many methods of
      restoring teeth using conventional indirect techniques, which may alter the
      existing occlusal vertical dimension (such as orthodontic Dahl appliances), or
      conserving the vertical dimension by increasing the length of the teeth. These
      methods are described and illustrated to assist the practitioner choose the most
      appropriate restoration.

PMID- 9534421
TI  - Repair of fractured incisors using a 4-META luting material.
AB  - The strength of bonds of resin-composite materials to dentine using dentine
      bonding systems have improved greatly within the past five years. It may
      therefore be possible to attempt repair of a fractured incisor tooth if the
      patient retrieves the fractured fragment and attends for treatment. Little long
      term data on the effectiveness of this treatment is available but, as materials
      improve, this approach to treatment of fractured incisor teeth should
      increasingly be considered.

PMID- 9534422
TI  - Hypodontia: George's case.
AB  - Five questions are posed regarding the treatment of a patient with hypodontia.
      The treatment options are discussed, and the actual treatment carried out
      demonstrated. The treatment preferences of British Orthodontists, elicited
      through the CASES project, are also included.

PMID- 9534423
TI  - Mycoplasma pneumoniae infection presenting as Stevens-Johnson syndrome: a case
      report.
AB  - A case of Mycoplasma pneumoniae infection as a precipitating factor in Stevens
      Johnson Syndrome is presented. As the dentist may well be the first to see this
      syndrome, it is appropriate to highlight the condition and this particular
      organism as an infective cause.

PMID- 9534424
TI  - The troublesome submerged tooth: a diagnostic dilemma.
AB  - Facial swelling caused by a periapical abscess is commonly encountered by dental
      practitioners. It requires prompt treatment, usually by removal of the infective
      foci and administration of appropriate antibiotics. However, diagnosis can be
      difficult, and may be complicated by the presence of retained deciduous teeth.
      This case report demonstrates a diagnostic dilemma and highlights the importance
      of looking beyond the obvious.

PMID- 9534425
TI  - Kissing molars: an unexpected finding.
AB  - Impacted permanent molars have been widely reported; however, the phenomenon of
      'kissing molars' or 'rosette formation' is not well reported. This may occur in
      isolation, or in addition to other features. This case report highlights the
      necessity for dental professionals to be vigilant for dental anomalies, which can
      be signs of various medical conditions and which may require further
      investigation.

PMID- 9534426
TI  - Conscious sedation.
AB  - Some patients are anxious about routine dental treatment; others, who may be able
      to cope with uncomplicated treatment, are worried by more unpleasant procedures
      such as minor oral surgery. Management approaches to anxiety vary according to
      its severity, the age of the patient, the degree of cooperation and the patient's
      medical history. Psychological approaches have been widely used and range from
      informal and common-sense methods to formal relaxation training and hypnosis.
      These techniques are safe, free from adverse effects and give the patient a sense
      of control. An increasing number of patients are managed with conscious sedation
      techniques in combination with local anaesthesia and the more severely anxious
      and uncooperative may require treatment under general anaesthesia. As patient
      awareness of the risk of anaesthesia and the availability of sedation have
      increased, so the popularity of conscious sedation for dentistry has increased.

PMID- 9534427
TI  - Resuscitation at the roadside.
AB  - This article summarizes what to do in the event of an emergency outside the
      dental surgery. It gives a simple and easy to follow guide to preserving life at
      the roadside when only minimal equipment is available. The fundamental principles
      of resuscitation will enable the practitioner to save a life in a situation when
      it is easy to forget the basic techniques in sheer panic. The training of the
      dental practitioner is an advantage in these uncommon but difficult situations
      when literally seconds count.

PMID- 9534428
TI  - The role of implants in restorative dentistry: prosthesis design and aesthetic
      considerations.
AB  - When implants are used to anchor an intra-oral prosthesis, the resulting
      dentition should not only function well but also be aesthetically pleasing. Both
      aspects must therefore be carefully considered in the assessment of each case.
      Optimal aesthetics can be achieved only if a number of criteria, of which the
      amount and quality of bone present in a potential implant site are most
      important, are fulfilled. Collapse of the labial cortical plate is common,
      occurring two to three years after extraction. It can result in palatal placement
      of implant fixtures, leading to a poor crown emergence profile. Insertion of an
      implant fixture after initial socket healing but before resorption has occurred
      will maintain the labial contour. This technique is being used with increasing
      success.

PMID- 9534430
TI  - 1995-96 membership roster.

PMID- 9534429
TI  - A professional calling.

PMID- 9534431
TI  - CDA code of ethics.

PMID- 9534432
TI  - Evolving business. Keeping up with the profession is the challenge.

PMID- 9534433
TI  - Targeting excellence in today's marketplace.
AB  - Managed care has greatly affected the health care marketplace in medicine and, to
      a lesser extent, in dentistry. These systems encourage over- and undertreatment
      of patients; and those patients, and their employers, are beginning to take
      notice. Meanwhile, the modern patient has become increasingly concerned with
      receiving excellent service. In this still-evolving marketplace, there lies
      challenge and opportunity for dentists.

PMID- 9534434
TI  - Conservative concepts for achieving anterior esthetics.
AB  - The options in conservative approaches to anterior esthetics include several that
      are often forgotten in favor of more complicated procedures. This article
      explores many of those treatments, including recontouring, abrasion and veneers.

PMID- 9534435
TI  - Planning your dental career.

PMID- 9534436
TI  - Antibiotic prophylaxis: the clinical significance of its recent evolution.

PMID- 9534437
TI  - Smile design--specific considerations.
AB  - Smile design is a new discipline that has come to the forefront with the recent
      popularity of cosmetic dentistry techniques. This article explores some of the
      principles used in smile design that can enhance the esthetics of any anterior
      restorative procedure.

PMID- 9534438
TI  - Total cycle care: balancing patient and employee needs.
AB  - Providing a friendly experience during patients' first visits and excellent
      dental care thereafter is not enough to secure long-term relationships. The best
      route for continuously providing the best dental experience includes empowering
      employees so that with their enthusiasm for the practice, they become ambassadors
      to the practice. Likewise, the team's ability to optimize techniques designed to
      increase patient comfort will ensure patients' continuing trust.

PMID- 9534439
TI  - Root canal therapy: rationale for treatment.

PMID- 9534440
TI  - Nonsurgical endodontic retreatment.
AB  - This article presents techniques for nonsurgical endodontic retreatment. Issues
      that influence treatment choice are discussed. Also outlined are armamentaria and
      techniques for coronal disassembly and removal of obturation materials.

PMID- 9534441
TI  - Extracted teeth: decontamination, disposal and use.
AB  - With the advent of medical waste and OSHA infection control regulations, many
      practitioners are unsure about the legal, proper handling of extracted teeth.
      This article outlines the options available for the disposal of extracted teeth
      and explains the role each regulatory agency plays in the process.

PMID- 9534442
TI  - Oral and nonoral sources of halitosis.
AB  - Oral malodor (halitosis, bad breath) is a condition affecting millions of
      Americans. In healthy individuals complaining of bad breath, the mouth is the
      main source of their oral malodor, more specifically the posterior dorsum of the
      tongue. Nonoral sources should also be considered. It is always easy to recognize
      halitosis, but identifying the exact cause is more complex.

PMID- 9534443
TI  - Detecting and treating oral and nonoral malodors.
AB  - This article suggests methods on how to detect and treat the various oral and
      nonoral malodor conditions with which patients present. These conditions are
      separated into those emanating from the nasal passage, sinuses and upper
      respiratory sources; the mouth; the tongue; the oropharynx; the lower respiratory
      tract; and the lungs. Foul odors also develop as a result of systemic and
      gastrointestinal disorders and diseases, as well as the normal breakdown of
      odiferous ingested foods. The available detection methods are described and
      future methods are suggested. The overall conclusions made from this review are
      that currently available management methods will be able to treat most cases. A
      careful, knowledgeable clinician can usually determine the patient's problem by
      the use of a thorough history and examination. Occasionally medical consults will
      be needed; and, in these cases, the approach that must be taken is a combined
      treatment approach. For example, effective therapy might require a combination of
      periodontal disease treatment, correction of dental restoration-based food traps
      and a rigorous daily mechanical debridement of the tongue. The above treatments
      will often have to be supplemented by the most appropriate mouthwash for the
      patient's specific condition. Finally, this article hopes to encourage
      manufacturers of "halitosis products" to support and conduct well-designed
      clinical trials on their products so that the field is advanced and treatments
      become more predictable.

PMID- 9534444
TI  - The effects of oral rinses on halitosis.
AB  - Oral rinses are increasingly becoming an important treatment option for
      halitosis. There are few products on the market that have been thoroughly
      evaluated in clinical trials designed to test for the long-term efficacy of
      mouthrinses in the management of this disorder. This review looks at some of the
      potential causes and detection methods or oral malodor along with the bacterial,
      microbiological and biochemical processes involved. The article presents the
      available literature on clinical trials evaluating the efficacy and mechanisms of
      action of the different types of oral rinses used in the reduction of plaque and
      gingivitis, in addition to rinse studies geared more specifically to the
      treatment of halitosis.

PMID- 9534445
TI  - Oral malodor: a periodontal perspective.
AB  - This article reviews the etiology, diagnosis and treatment of oral malodor from a
      periodontal perspective. The connections among periodontal pathogenic
      microorganisms, periodontal disease and oral malodor have been strongly
      implicated but not proved. Although oral malodor is probably not caused by
      periodontal disease, there is ample evidence to suggest that periodontal disease
      increases the severity of oral malodor.

PMID- 9534446
TI  - Imagined halitosis: a social phobia symptom?
AB  - Imagined halitosis is poorly documented in the psychiatric literature. It is
      perhaps best thought of as a symptom rather than as a specific syndrome (a
      collection of symptoms that co-vary together). Many of the cases with imagined
      halitosis described in the literature resemble the psychiatric syndrome of social
      phobia.

PMID- 9534447
TI  - Dentistry in the information age.
AB  - The data available to be gathered and analyzed in this new Information Age will
      help dentistry fend off managed care by validating the value of dental care and
      reducing the cost of practice administration. Many of the tools are in place and
      others will be soon. It is up to dentistry, however, to take the necessary
      initiative.

PMID- 9534448
TI  - Coming soon: the virtual group.
AB  - This paper discusses the possible "virtual group" use of an electronic patient
      record and its effect on the traditional group practice of dentistry. With an
      electronic patient record, several dentists with separate practices but common
      access to a patient's file can routinely consult on cases, thereby giving the
      patient the benefit of several practitioners' input.

PMID- 9534449
TI  - Organized dentistry in the information age.

PMID- 9534450
TI  - Digital radiographs: will the future ever arrive?
AB  - The benefits of introducing digital technologies and specifically digital
      radiographs should be compelling and yet the widespread acceptance has been slow.
      A brief anecdotal look at two other industries suggests possible insight into the
      factors leading to the acceptance of digital radiography in the dental industry.
      Rather than to argue for a single digital radiography product, it is suggested
      that irrespective of the means of digital radiograph capture, there are pervasive
      benefits for the dental practitioner in using digital radiograph technology.

PMID- 9534451
TI  - Computers in dental education.
AB  - The advent of electronic support for dental education offers many possible
      improvements in the manner in which information is conveyed to students. Although
      dental schools are only beginning to implement these concepts and devices, there
      is indication that they will become increasingly common. Concepts can be more
      lucidly conveyed when images and mulitmedia are used effectively. Distances can
      be transcended, and information gathered from and conveyed to others without
      regard to physical limitations. The dental school curricula must accommodate the
      changing milieu in which dentistry is practiced and prepare students for the
      future, electronically assisted dental practice.

PMID- 9534452
TI  - Nothing but net?
AB  - The internet is gaining momentum around the world as a repository of an
      incredibly wide variety of information. The Internet's uses for dentistry,
      however, will far exceed what is being done now. Practitioners should become
      familiar with the Internet now to be ready when much dental business is done
      through that medium.

PMID- 9534453
TI  - The successful dental implant.

PMID- 9534454
TI  - Osseointegration: contemporary concepts and treatment.
AB  - The classical principles of osseointegration were based on a strict surgical
      protocol established through decades of experimental research and human clinical
      trials. These principles establish a sound scientific and clinical foundation for
      the neophyte implant surgeon. Research, however, is constantly accumulating,
      challenging a number of these original concepts and allowing deviation from the
      established protocol. It is anticipated that these changes will improve implant
      dentistry performance and expedite patient care. Sound clinical judgment based on
      experience and knowledge of the scientific literature must be exercised when
      deviations from the established protocol are considered.

PMID- 9534455
TI  - Factors to consider while treatment planning dental implants in the partially
      edentulous patient.
AB  - Although short-term studies of dental implants in the partially edentulous
      patient appear very promising, multicenter long-term studies are not yet
      available. Since the differences between dental implants and teeth are
      significant, treatment planning for the partially edentulous patient is more
      difficult. This paper will discuss important areas to be examined in treatment
      planning the partially edentulous patient.

PMID- 9534456
TI  - Esthetic replacement of the anterior tooth with an implant-supported restoration.
AB  - The use of implants in esthetic areas is complex because the implant must be
      placed in a precise location to support an esthetic restoration. This paper will
      focus on the treatment planning and sequencing for the restoration of single
      anterior teeth with implant-supported restorations. The factors necessary for a
      predictable esthetic outcome will be discussed.

PMID- 9534457
TI  - Implants in the partially edentulous patient: restorative considerations.
AB  - Restorative considerations are critical to the long-term success of fixed implant
      supported prostheses, especially in the posterior quadrants of the partially
      edentulous patient. The parafunctional habit of bruxism must be identified and
      addressed. The restoration should dictate implant placement. Control of forces
      directed upon the prosthesis and implants is critical to long-term success.
      Anatomic limitations to implant placement and surgical procedures to correct
      these deficiencies must be considered for their impact on the prosthetic
      restoration. Nonaxial forces or bending moments should be minimized by the use of
      an adequate number, position and alignment of implants; by control of the
      occlusion; and by design of the prosthesis. The patient must understand the
      risks, limitations, costs and time commitments of implant restorations prior to
      treatment.

PMID- 9534458
TI  - Diagnosis and management of peri-implant disease.
AB  - Long-term success of dental implants depends largely on the continued health of
      peri-implant hard and soft tissues and an appropriate force distribution on the
      implants. Since dental implants are accepted as viable and, in some cases, ideal
      restorative options, all members of the dental team are faced with the task of
      maintaining implant health. This review outlines the current understanding of
      implant health and disease and presents recommendations for the treatment and
      management of diseased implants.

PMID- 9534459
TI  - Sorting it out.

PMID- 9534460
TI  - Case 1: Superficially invasive squamous carcinoma.

PMID- 9534461
TI  - Case 2: Lichenoid mucositis consistent with contact mucositis.

PMID- 9534462
TI  - Case 3: Odontogenic keratocyst.

PMID- 9534463
TI  - Case 4: Kaposi's sarcoma.

PMID- 9534464
TI  - Case 5: Unicystic ameloblastoma.

PMID- 9534465
TI  - Case 6: Proliferative verrucous leukoplakia.

PMID- 9534467
TI  - Case #10: Complex odontoma.

PMID- 9534466
TI  - Turning amalgam green.

PMID- 9534468
TI  - Do you have bone loss?

PMID- 9534469
TI  - Check for popcorn hulls, fingernails after spotting abscesses in children.

PMID- 9534470
TI  - Backed into a corner? It's time for a decision.

PMID- 9534471
TI  - Make eye protection a priority to prevent contamination and injury.

PMID- 9534472
TI  - Antianginal therapy.

PMID- 9534473
TI  - Case #11: Impetigo.

PMID- 9534474
TI  - Research on periodontal ligament healing boosts success rate of tooth
      transplants.

PMID- 9534475
TI  - Where the bite is worse than the bark.

PMID- 9534476
TI  - A day at the vet.

PMID- 9534477
TI  - Closet monsters.

PMID- 9534478
TI  - Failure to adequately sterilize instruments can be traced back to common
      mistakes.

PMID- 9534479
TI  - Writing fake notes? Don't expect to get away with it.

PMID- 9534480
TI  - Icy atmosphere.

PMID- 9534481
TI  - Advances in profession during past 15 years lead to exciting transition in
      responsibilities.

PMID- 9534482
TI  - 2010: hygienists' odyssey.

PMID- 9534483
TI  - United, we study.

PMID- 9534484
TI  - Do OTC 'ulcer drugs' pose problems when used with dental medications?

PMID- 9534485
TI  - Negative thoughts.

PMID- 9534486
TI  - Patients should always be remembered when extolling benefits of 'barriers'.

PMID- 9534487
TI  - The North American Rheumatoid Arthritis Consortium--bringing genetic analysis to
      bear on disease susceptibility, severity, and outcome.

PMID- 9534488
TI  - Development and validation of an exercise performance support system for people
      with lower extremity impairment.
AB  - OBJECTIVE: To identify innovative strategies to support appropriate, self
      directed exercise that increase physical activity levels of people with
      arthritis. This article reports on one interactive, multimedia exercise
      performance support system (PSS) for people with lower extremity impairments in
      strength or flexibility. METHODS: An interdisciplinary team developed the PSS
      using self-report of lower extremity musculoskeletal impairments (flexibility and
      strength) to produce an individualized exercise program with video and print
      educational materials. Initial evaluation has investigated the validity and
      reliability of program assessments and recommendations. RESULTS: PSS self-report
      and professional assessments were similar, with more impairments indicated by
      self-report. PSS exercise recommendations were similar to those made by 3 expert
      physical therapists using the same exercise data base. Results of PSS impairment
      assessments were stable over a 1-week period. CONCLUSION: PSS exercise
      recommendations appear to be reliable and a valid reflection of current exercise
      knowledge in rheumatology. Furthermore, users were able to complete the computer
      based program with minimal assistance and reported it to be enjoyable and
      informative.

PMID- 9534489
TI  - The stresses of rheumatoid arthritis: appraisals of perceived impact and coping
      efficacy.
AB  - OBJECTIVE: This study examined appraisals of the impact of 7 stressors associated
      with rheumatoid arthritis (RA) and the perceived ability to cope with those
      stressors. METHODS: Subjects were 446 participants in a panel study of persons
      with RA. Data were derived from the 1994 annual interview. RESULTS: There were
      significant differences among mean ratings of the stressors. Taking care of RA,
      fatigue, pain, and functional impairment were rated as having the greatest
      impact; perceived coping efficacy was highest for medication side effects and
      taking care of RA. Appraisals of impact and coping efficacy were negatively
      correlated. Clinical factors were the strongest predictors of both appraisals.
      Depressive symptoms and instrumental support were also independently associated
      with both appraisals for most stressors. CONCLUSIONS: All of the stressors were
      problematic to some degree, suggesting that coping research should include
      stressors other than pain and function. Most subjects rated the effects of these
      stressors as moderate, however. Future examination of the coping responses of
      these individuals may shed light on adaptation to RA.

PMID- 9534490
TI  - Psychosocial contributors to mental and physical health in patients with systemic
      lupus erythematosus.
AB  - OBJECTIVE: To delineate psychosocial and systemic lupus erythematosus (SLE)
      related medical factors that contribute to the mental and physical health of SLE
      patients. METHODS: In a cross-sectional study, 44 women completed standardized
      instruments assessing daily hassles, social support, psychologic distress, and
      quality of life and underwent a physician examination to assess disease activity
      and disease damage. Four multiple linear regression analyses were computed to
      identify factors associated with the following outcomes: patient-perceived
      psychologic distress and global physical health and physician-assessed disease
      activity and damage. Variables entered into the regression analyses were: hassles
      severity, types of social support, SLE disease activity and damage, age, disease
      duration, education, ethnicity, and global psychologic distress (for the outcomes
      of self-perceived global physical health and disease activity and damage).
      RESULTS: The best model explaining global psychologic distress included hassles
      severity and self-esteem social support. The best model explaining patients'
      perceptions of their global physical health included hassles severity and
      tangible social support. Psychologic distress accounted for a significant
      proportion of variance in both disease activity and damage. CONCLUSION: High
      stress (assessed by hassles severity), poor social support, and psychologic
      distress--potentially modifiable variables--are associated with the mental and
      physical health of SLE patients.

PMID- 9534491
TI  - Positive impact of an intervention by arthritis educators on retention of
      information, confidence, and examination skills of medical students.
AB  - OBJECTIVE: To determine whether an intervention by trained persons with arthritis
      could have a positive impact on retention of information, confidence, and
      examination skills of medical students. METHODS: Second-year medical students
      were introduced to the musculoskeletal examination as part of their Introduction
      to Clinical Medicine course by viewing a video (n = 93) or were taught the joint
      examination by a trained arthritis educator after viewing the video (n = 88).
      Each group was tested before and after the intervention about arthritis
      information, confidence, and attitude about arthritis and also evaluated for the
      ability to carry out a musculoskeletal examination. RESULTS: Retention of
      information and confidence of both groups increased as a result of the
      intervention. However, students who received the arthritis educator intervention
      increased their scores significantly in comparison. Musculoskeletal examination
      skills of the students receiving the arthritis educator intervention were also
      significantly greater than the control group. CONCLUSION: An intervention by
      arthritis educators improved the retention of information, confidence, and
      examination skills of second-year medical students significantly compared with
      the standard educational approach. The impact of the intervention persisted for
      at least two weeks.

PMID- 9534492
TI  - Joint hypermobility in patients with fibromyalgia syndrome.
AB  - OBJECTIVE: To test the hypothesis that joint hyperlaxity can play some role in
      the pathogenesis of pain in primary fibromyalgia. METHODS: A total of 66 women
      with fibromyalgia (according to the 1990 American College of Rheumatology
      criteria) and 70 women with other rheumatic diseases were examined for joint
      laxity based on 5 criteria (The Non-Dominant Spanish modification). Individuals
      meeting 4 or 5 criteria were considered to be hyperlax. RESULTS: Joint
      hyperlaxity was detected in 18 (27.3%) of the patients with fibromyalgia and 8
      (11.4%) of those with another rheumatic disorder. The statistical analysis
      revealed significant differences (P < 0.05) between both groups. CONCLUSION: The
      results of this study suggest that joint hypermobility and fibromyalgia are
      associated. Joint hyperlaxity may play a prominent role in the pathogenesis of
      pain in fibromyalgia.

PMID- 9534493
TI  - A standardized protocol for measurement of range of movement of the shoulder
      using the Plurimeter-V inclinometer and assessment of its intrarater and
      interrater reliability.
AB  - OBJECTIVE: To develop a standardized protocol for measurement of shoulder
      movements using a gravity inclinometer designed for use in clinical trials, and
      to assess its intra- and interrater reliability in a group of manipulative
      physiotherapists. METHODS: After instruction, 6 manipulative physiotherapists
      independently assessed 8 movements of the shoulder, including total and
      glenohumeral flexion (TF, GHF), total and glenohumeral abduction (TA, GHA),
      external rotation in neutral (ERN) and abduction (ERA), internal rotation in
      abduction (IRA), and hand behind back (HBB), in random order in 6 patients with
      shoulder pain and stiffness according to a 6 x 6 Latin square design using the
      standardized protocol. The assessments were then repeated. Analysis of variance
      was used to partition total variability into components of variance in order to
      calculate intraclass correlation coefficients (ICCs). RESULTS: The intra- and
      interrater reliability of the different movements varied widely. Reliability was
      higher for TF and TA than for the corresponding glenohumeral movements (e.g.,
      intrarater ICCs: TF = 0.80, GHF = 0.65, TA = 0.75, GHA = 0.62). Interrater
      reliability was higher in the second round suggesting a practice effect (e.g.,
      round 1, 2 interrater ICCs TF = 0.62, 0.82; TA = 0.62, 0.88; ERN = 0.85, 0.95).
      CONCLUSION: The measurement of the active range of TF, TA, ERN, and HBB, measured
      by manipulative physiotherapists following the standardized protocol, has intra-
      and interrater reliability acceptable for use as an outcome measure in clinical
      trials assessing interventions for shoulder pain.

PMID- 9534494
TI  - Three opportunities to work with the news media.

PMID- 9534495
TI  - The relationship between psychosocial variables and pain reporting in
      osteoarthritis of the knee.
AB  - Psychosocial factors may explain some of the variation in pain reporting among
      individuals with knee OA. This has important potential implications for
      management; indeed, several studies (reviewed in ref. 56) have demonstrated that
      interventions may reduce knee pain without apparent halting or reversing of
      structural damage. Such interventions have included the simple provision of
      support by monthly telephone calls (57), self-management programs (58), and
      cognitive-behavioral approaches designed to teach patients ways of coping with
      their pain (59). These programs are even more effective if the spouse is involved
      (60). It should be noted that there may be a large placebo effect in these
      interventions, and the degree to which patients are responding simply to an
      interest being taken in them and their problems is unclear; at least one study
      has shown that formal cognitive-behavioral therapy is no better than didactic
      education at improving pain and function in knee OA (though both are beneficial)
      (61). Many studies examining the role of psychosocial factors have suffered from
      poor design; many, for example, fail to control for radiographic severity. Future
      studies should define how pain is identified (dichotomous, ever/never/current,
      severity), differentiate community and hospital subjects, and separate patients
      by type and location of OA. Studies should also control for other factors
      potentially associated with pain: obesity, comorbidity, muscle weakness, and
      aerobic fitness. Prospective studies would allow clarification of the cause and
      effect relationship between anxiety, depression, and pain, both in the community
      and in patients who have elected to seek medical help. In this way, we may
      increase our understanding of the complex interaction between mood, social
      factors, and pain reporting in knee OA and, thus, improve the effectiveness,
      already equivalent to many pharmacologic interventions, of treatments designed to
      address psychosocial factors.

PMID- 9534496
TI  - Qualitative methods in arthritis research: sampling and data analysis.
AB  - Qualitative research presents unique opportunities for understanding arthritis
      from the perspective of those affected by the condition, as well as for
      critically evaluating many of the associations of traditional psychosocial
      variables that have emerged from decades of quantitative research. Its growing
      acceptance and popularity in the health sciences is reflected in the number of
      program announcements and other research requests that stress the need to
      understand health and disease in the context of human diversity. At the same
      time, it is important that qualitative research be done well and be critically
      evaluated in the same manner as quantitative research. Many of the same cautions
      (e.g., garbage in, garbage out) and principles (e.g., standardization of data
      collection and analysis steps, documentation of research activities) apply in all
      types of scientific inquiry. By maintaining high standards for qualitative
      research, those conducting and evaluating qualitative research can ensure its
      continued acceptance as a valid and powerful mode of research.

PMID- 9534497
TI  - Birth: the journal that Madeleine Shearer began 25 years ago.

PMID- 9534498
TI  - Maternity care today: is our glass half empty or half full?

PMID- 9534500
TI  - A national survey of use of obstetric procedures and technologies in Canadian
      hospitals: routine or based on existing evidence?
AB  - BACKGROUND: The objective of this national survey was to describe the routine use
      of procedures and technologies in Canadian hospitals providing maternity care,
      and to determine the extent to which current use was consistent with the existing
      evidence and recommended guidelines for maternal and newborn care. METHODS:
      Representatives of 572 hospitals providing maternity care across Canada were sent
      questionnaires in the spring and summer of 1993; 523 (91.4%) responded. The
      primary outcome measures consisted of the self-reported use of obstetric
      procedures and technologies (perineal shaves, enemas/suppositories, intravenous
      infusions, initial and continuous electronic fetal heart monitoring, episiotomy
      rates). Hospitals were grouped according to location, size (number of live births
      per year), and university affiliation status. RESULTS: The hospitals in the
      Prairie provinces, in Quebec, and in the Atlantic provinces were significantly
      less likely than those in Ontario to restrict their use of perineal shaves and
      enemas to women on admission in labor. Small hospitals were significantly more
      likely than large hospitals (> 1000 live births) to restrict their use of
      intravenous infusions, and initial and continuous electronic fetal monitoring.
      The university-affiliated and nonteaching hospitals were significantly less
      likely than the university teaching hospitals to have episiotomy rates of less
      than 40 percent for primiparous women. Small hospitals were more likely than
      large hospitals to report episiotomy rates of less than 20 percent for
      multiparous women. CONCLUSIONS: Considerable variations occur in the routine use
      of obstetric procedures and technologies in Canadian hospitals providing
      maternity care, according to hospital location, size, and university affiliation
      status. Despite the existing evidence suggesting that the routine use of these
      practices and procedures is both unnecessary and potentially harmful, a
      significant number of Canadian hospitals continued to use them routinely in 1993.

PMID- 9534499
TI  - An early labor assessment program: a randomized, controlled trial.
AB  - BACKGROUND: Approximately 31 percent of cesarean deliveries in the United States
      and Canada are performed for dystocia. The aim of this study was to determine the
      effectiveness of early labor assessment to reduce cesarean birth rates for low
      risk nulliparous women. METHODS: Two hundred and nine low-risk nulliparous women
      were randomly allocated to either the early labor assessment group or the direct
      admission to hospital group. Women in the early labor assessment group were
      evaluated and, if found to be in false or latent labor, were encouraged to go
      home or walk before admission to the labor unit. Those in the direct admission
      group were admitted to the labor unit without an assessment. Data were collected
      and analyzed about method of delivery, duration of labor, intrapartum
      interventions, and neonatal well-being. Women completed an evaluation of their
      experience in the early postpartum period. RESULTS: Significant decreases
      occurred in duration of labor, use of epidural analgesia for pain, and use of
      oxytocin to augment labor in the early labor assessment group. These women
      evaluated their labor and birth experience more positively than women in the
      direct admission group. No significant differences were found in the frequency of
      cesarean section or instrumental vaginal delivery for the two groups.
      CONCLUSIONS: Early labor assessment has the potential to reduce the number of
      women receiving oxytocin for augmentation, the rate of epidural analgesia for
      pain relief, and the duration of the active and second stages of labor, and to
      improve women's evaluations of their labor and birth experiences.

PMID- 9534501
TI  - Transfer from home to hospital: what is its effect on the experience of
      childbirth?
AB  - BACKGROUND: In the Netherlands women with low-risk pregnancies are free to choose
      where to give birth, at home or in hospital, attended by an independent midwife
      or general practitioner. On average one of five women who remains in the care of
      a midwife at the onset of labor will be referred to an obstetrician during or
      shortly after childbirth. If women had planned to give birth at home, they would
      then have to be transferred to the hospital. METHODS: Postal questionnaires were
      sent to 2301 pregnant women before and after birth to measure the experience of
      childbirth, appropriateness of the chosen place of birth, satisfaction with the
      birth, midwife's care, and first days postpartum of women planning to give birth
      at home or in hospital. The response rate for both questionnaires was 89.3
      percent. RESULTS: Of 745 nulliparous women and 895 multiparous women, 39.3 and
      10.3 percent, respectively, experienced referral to an obstetrician during labor.
      Of these women, the ones who wanted to give birth at home but were transferred to
      hospital because of the referral were as positive about the birth, early
      puerperium, and attendance of the midwife as the women who wanted to give birth
      in hospital. CONCLUSION: Our research showed, contrary to expectations, that an
      unplanned transfer from a planned home birth to hospital has little influence on
      the experience of childbirth.

PMID- 9534502
TI  - Prenatal smoking cessation counseling by Texas obstetricians.
AB  - BACKGROUND: Smoking during pregnancy causes 20 to 30 percent of low birthweight
      and 10 percent of infant mortality in the United States. Brief counseling can
      reduce rates of smoking. The study objectives were to describe Texas
      obstetricians' pregnancy smoking cessation counseling activity and to identify
      attributes associated with consistent, effective counseling. METHODS: A survey
      was mailed to a random sample of Texas obstetricians. RESULTS: A response rate of
      44 percent (n = 204) was attained. A counseling coverage-effectiveness index was
      created based on the percentage of smokers counseled and use of specific
      techniques. Almost all respondents reported asking about smoking; fewer, however,
      reported counseling smokers. Physicians with low index scores, indicating
      inconsistent coverage, ineffective counseling, or both were dissatisfied with
      their current counseling, did not perceive counseling to decrease smoking, were
      not aware of the risks of smoking, and were unfamiliar with expert reports and
      recommendations for prenatal care. CONCLUSIONS: Obstetricians who are not reached
      by expert reports and guidelines from groups outside their specialty or who do
      not perceive the seriousness of maternal smoking are less likely to counsel
      consistently and to use the most effective techniques. Continuing medical
      education at local, state, and national levels should be directed toward
      increasing knowledge and skills about smoking cessation counseling of pregnant
      women.

PMID- 9534503
TI  - Willingness to pay: a method for measuring preferences for maternity care?
AB  - BACKGROUND: The aim of this study was to assess the feasibility of the use of
      "willingness to pay" as a measure of the benefits of intrapartum care. METHODS: A
      questionnaire was mailed to 150 pregnant women booking at Aberdeen Maternity
      Hospital in the northeast of Scotland, giving information on options for
      intrapartum care compiled from a recent randomized trial of care in a midwife
      managed delivery unit versus care in a consultant-led labor ward. Women were
      asked which type of care they preferred and what would be their maximum
      willingness to pay for their preferred option. Data were also collected on
      demographic and clinical characteristics. RESULTS: Most women (55%) expressed a
      preference for care in a midwives unit. However, strength of preference, as
      reflected in willingness to pay, was greater among those in the smaller group,
      who expressed a preference for care in a consultant-led labor ward. The
      willingness-to-pay results were not associated with ability to pay. CONCLUSIONS:
      These data should be used together with cost data to decide on provision of care.
      Given the strength of preference of the minority group, and if the cost
      implications are not too great, a flexible service that takes account of women's
      wishes should be provided, even if this goes against the trend for care of those
      at low risk. By analyzing choice of care by income groups and social class
      groupings, it is possible to examine whether willingness-to-pay results are
      associated with indicators of ability to pay. In this case, they were not.
      Willingness to pay has an advantage in allowing respondents to account for more
      than just health gain when valuing different types of care.

PMID- 9534504
TI  - Are breastfeeding problems related to incorrect breastfeeding technique and the
      use of pacifiers and bottles?
AB  - BACKGROUND: In Western countries during the 1960s and 1970s, sore nipples and
      insufficient milk were common problems that made it hard for mothers to maintain
      breastfeeding for long. This study investigated the relationship of breastfeeding
      problems to nursing behavior and pacifier use. METHODS: Fifty-two healthy mother
      infant pairs with breastfeeding problems were referred for observation of nursing
      behavior to a breastfeeding clinic at the Department of Pediatrics of Malmo
      General Hospital, Malmo, Sweden, from August 1987 to July 1989. The infants
      ranged in age from 1 to 17 weeks. A faulty nursing pattern was corrected as
      necessary. Forty mother-infant pairs with no breastfeeding problems provided a
      control group. RESULTS: In most cases the nursing problems were related to
      incorrect sucking technique. The difference in technique of the study group
      compared with the control group was significant (p = 0.0001). The continuation of
      breastfeeding was poorer if the infant already had become used to bottle-feeding.
      Pacifier use was more common in conjunction with breastfeeding problems and in
      cases with a faulty superficial nipple-sucking technique. CONCLUSION:
      Breastfeeding problems may be prevented by the adoption of hospital routines that
      do not interfere with the start of breastfeeding and by the avoidance of
      extensive use of pacifiers.

PMID- 9534505
TI  - Concepts and controversies in the management of group B streptococcus during
      pregnancy.
AB  - BACKGROUND: Group B beta-hemolytic streptococcus colonizes 20 percent of pregnant
      women. Intrapartum fetal colonization leads to invasive disease in 1 to 2 infants
      of every 1000 births in the United States, and has a mortality of approximately 6
      percent. Several protocols using intrapartum chemoprophylaxis have been devised
      to improve management of the disease, but confusion continues about details and
      implementation. This review examined the clinical issues, current management
      protocols, and advantages and disadvantages of these protocols for group B
      streptococcus. METHODS: We reviewed the literature and described the
      epidemiology, detection methods, risk factors, neonatal disease potential of
      group B streptococcus, and the historical development of management protocols.
      Two current alternatives, the American College of Obstetricians and
      Gynecologists' risk-based protocol and the Centers for Disease Control and
      Prevention's screening-based protocol, are described and compared. RESULTS: The
      risk-based protocol does not entail antepartum screening, but treats women with
      certain risk factors during labor. The screening-based protocol includes cultures
      at 35 to 37 weeks' gestation, and offers intrapartum prophylaxis to all women
      with positive cultures. Uncultured women with risk factors are treated. Both
      protocols involve high rates of intrapartum antibiotic use and both may
      significantly lower rates of neonatal group B streptococcus sepsis (screening
      based more than risk-based for both). The risk-based approach is simpler than the
      screening-based approach. CONCLUSIONS: Practitioners should select one of the two
      protocols and use it consistently. The differences in efficacy are small; a
      practitioner may not see a difference in outcomes over the course of his or her
      career, although more antibiotics will be administered using the screening-based
      approach.

PMID- 9534506
TI  - Preventing intrauterine growth retardation with aspirin: does it work?

PMID- 9534507
TI  - Sheila Kitzinger's letter from Europe: the cesarean epidemic in Great Britain.

PMID- 9534508
TI  - Caring for the mother and the preterm infant: kangaroo care.

PMID- 9534509
TI  - Trends in care delivery models.

PMID- 9534510
TI  - Primary and secondary prevention strategies in the older adult.
AB  - Most causes of death and disability in older people are partially to fully
      preventable. To achieve maximum benefits from prevention strategies, use an
      organized system tailored to individual health risks and circumstances.

PMID- 9534512
TI  - Clinical evaluation of the efficacy and safety of an ultrasonic toothbrush system
      in an elderly patient population.
AB  - Twelve dentulous patients, age 65 or older, with no medical or pharmacologic
      predisposition to gingival hyperplasia were enrolled in a controlled clinical
      trial to evaluate the effect of the unaided use of an ultrasonic toothbrush on
      supragingival plaque and gingival bleeding. Subjects used the ultrasonic
      toothbrush in lieu of their conventional toothbrushes for a 30-day period.
      Clinical measurements of the plaque index and bleeding index were made at
      baseline and at 15 and 30 days. At the end of the 30-day test period, the use of
      the ultrasonic toothbrush resulted in significant reductions in plaque score,
      proportion of high plaque surfaces, and bleeding index. The reduction of the
      bleeding index indicates significant improvement in oral health. In this study,
      the use of an ultrasonic toothbrush effectively improved oral hygiene and health
      in a population that often exhibits decreased manual dexterity. Strategies for
      oral health care assessment and education for guidance of effective interventions
      are included in checklist form; level of care classification, cost in both time
      involved and equipment, and purchase instructions also are discussed. Further
      study is warranted to evaluate this instrument for cognitively impaired elders,
      who often rely on caregivers for oral hygiene procedures.

PMID- 9534511
TI  - Perspectives on the nursing management of osteoarthritis.
AB  - Osteoarthritis is a daily presence in the lives of almost 16 million older
      people. Without expert nursing care, functional health status and the ability to
      manage independently may be dramatically altered. Nursing parameters include pain
      control, medication assessment, use of exercise, diet, joint protection, and
      attention to the psychosocial factors that affect both pain and disability.
      Patient education with regular, periodic follow-up is a vital part of successful
      long-term management.

PMID- 9534513
TI  - The sharing of self in geriatric clinical practice: case report and analysis.
AB  - We relate a case history that involved the therapeutic sharing of self with an
      elderly patient. The potential usefulness of this kind of intervention is
      discussed in light of the literature on self-disclosure and the use of self in
      clinical practice. We discuss how these concepts might relate to other well
      described phenomena in geriatric nursing, including reminiscence, life review,
      loneliness, and storytelling. Recommendations for use in clinical practice and
      for qualitative studies are given.

PMID- 9534514
TI  - Nurse to nurse: consultation in geriatric nursing practice.
AB  - The complexity of clients in today's health care environment requires a close,
      collaborative working relationship among disciplines. However, nurses, who are
      often key decision-makers in the planning, management, and movement of clients
      throughout the health care system, may not use the expertise of their best
      allies: nurses in other settings, institutions, and specialty areas. Many care
      problems-at home or in the hospital, nursing home, or rehabilitation center-can
      be effectively resolved by nurse-to-nurse consultation. The importance and
      benefit of nurses relying on their own profession to answer nursing care
      questions are illustrated with vignettes that apply a model of consultation to
      the practice of geriatric nursing.

PMID- 9534516
TI  - Stopping heart disease with diet.

PMID- 9534517
TI  - Key concepts of self-care in the home: implications for home care nurses.

PMID- 9534518
TI  - Keeping up with new drugs for diabetes.

PMID- 9534519
TI  - Validating what we do: a word about evidence-based practice.

PMID- 9534520
TI  - Free clinics and parish nursing offer unique rewards.

PMID- 9534522
TI  - Utah. Forensic Nurse Examiners, P.C.

PMID- 9534521
TI  - More on fosphenytoin (Cerebyx) dosing.

PMID- 9534523
TI  - Interpreting the law: help on the Internet.

PMID- 9534524
TI  - Latex-free drug vials and injectables encouraged.

PMID- 9534525
TI  - Malignant hyperthermia in the emergency department.

PMID- 9534526
TI  - Tick paralysis in a 2-year-old girl.

PMID- 9534527
TI  - A look back: diagnoses--"pregnancy".

PMID- 9534528
TI  - Battered women: where they go for help.
AB  - OBJECTIVE: Assistance must be available to abused women where they seek help.
      This study identified victims of partner abuse and asked them to indicate where
      they sought help when battered. The characteristics of acute battering incidents
      were also investigated. METHODS: Consecutive women, ages 19 to 65, were recruited
      when they came to 10 emergency departments in two cities. Women were excluded if
      the following criteria existed: a language barrier, serious illness, or inability
      to separate subjects from accompanying persons. RESULTS: Of 4448 women who
      completed the questionnaire, 37% acknowledged physical abuse by a partner at some
      time; 10% reported a present battering relationship; and 4% said their current
      visit to the emergency department was for abuse by an intimate partner. In 70% of
      surveys, the battering person was a boyfriend or ex-boyfriend. Weapons used were
      items near at hand. The three most common helping resources, in decreasing
      frequency of use, were family and friends, police, and the emergency department.
      DISCUSSION: Resources to provide help must be available where women seek care
      when they are abused. Abuse among women who come to emergency departments is
      common, and emergency departments are the third highest resource cited by abused
      women. Emergency nurses should be prepared to identify and assist abused women.

PMID- 9534529
TI  - Hypertension in the elderly: don't treat too quickly!
AB  - In the asymptomatic patient without target organ damage who is seen with severely
      elevated BP, pseudohypertension is more often than not the cause. Rapid lowering
      of arterial pressure is unnecessary and even contraindicated. Nurses play an
      important role in the evaluation and the treatment of elderly patients with
      hypertension. Both research-based practice and thorough evaluation and monitoring
      are requisite for safe and effective treatment. Given the seriousness of the
      adverse effects and the lack of outcome data, the use of sublingual nifedipine
      capsules in hypertensive emergencies and pseudohypertension should be abandoned.

PMID- 9534530
TI  - The emergency department consortium: one approach to emergency nursing education.

PMID- 9534531
TI  - Interviewing suspected victims of child maltreatment in the emergency department.
AB  - Every day, children suspected of being maltreated present to emergency
      departments throughout the United States. These children should be given the
      opportunity to discuss what happened to them. Statements made by an abused child
      can become powerful evidence in court, and the legality of such statements could
      be strengthened by the use of forensic interview techniques. The ED interview is
      not an investigative interview. It should be used to obtain information needed to
      assess, treat, and report cases of suspected child maltreatment. Ideally, the
      child should be separated from the caregiver and the setting should provide
      safety and privacy. The nurse begins the interview with an opened-ended question
      such as "What happened?" and then progress, if necessary, to more directed for
      focused questions. Such progression creates confidence in the reliability of the
      child's responses. Finally, accurate and detailed charting is crucial in a child
      maltreatment case. The nurse must document the interview using the child's exact
      words and noting the child's behavior and demeanor at the time the statements
      were made.

PMID- 9534532
TI  - Data elements for emergency department systems, release 1.0 (DEEDS): a summary
      report. DEEDS Writing Committee.
AB  - Variations in the way that data are entered in ED record systems impede the use
      of ED records for direct patient care and deter their reuse for many other
      legitimate purposes. To foster more uniform ED data, the Centers for Disease
      Control and Prevention's (CDC) National Center for Injury Prevention and Control
      is coordinating a public-private partnership that has developed recommended
      specifications for many observations, actions, instructions, conclusions, and
      identifiers that are entered in ED records. The partnership's initial product.
      Data Elements for Emergency Department Systems, Release 1.0 (DEEDS), is intended
      for use by individuals and organizations responsible for ED record systems. If
      the recommended specifications are widely adopted, then problems--such as data
      incompatibility and high costs of collecting, linking, and using data--can be
      substantially reduced. The collaborative effort that led to DEEDS, Release 1.0
      sets a precedent for future review and revision of the initial recommendations.

PMID- 9534533
TI  - Guidelines for pediatric equipment and supplies for emergency departments.
      Committee on Pediatric Equipment and Supplies for Emergency Departments. National
      Emergency Medical Services for Children Resource Alliance.

PMID- 9534534
TI  - A 10-year-old's suicide and a grieving emergency nurse: lessons learned.

PMID- 9534535
TI  - Latex-safe emergency cart products list.

PMID- 9534536
TI  - After fen-phen/Redux: cardiac and pulmonary sequelae implications for patient
      assessment.

PMID- 9534537
TI  - Musings of a camp nurse.

PMID- 9534538
TI  - The weakest link in the chain of survival?

PMID- 9534539
TI  - MedAire: peace of mind in the skies--a flight nurse's dream come true. Interview
      by Marlene Jezierski.

PMID- 9534540
TI  - Nurse educator. Pearls of wisdom for graduate school.

PMID- 9534541
TI  - Public speaking for fun and profit.

PMID- 9534542
TI  - Emergency treatment of fever phobia.

PMID- 9534543
TI  - A clinical competency program for nurses caring for infants and children
      receiving conscious sedation.

PMID- 9534544
TI  - Susan MacLean, RN, PhD, director, ENA research services.

PMID- 9534545
TI  - Light staining microscope: clinical experience in a Sexual Assault Nurse Examiner
      (SANE) program.
AB  - Our light staining microscope has decreased the amount of set-up time for staff,
      has increased the ability to see both sperm and other biologic specimens, and has
      become an essential tool in both our clinical and forensic practice.

PMID- 9534546
TI  - Allegations of sexual assault on the inpatient unit: how to respond.

PMID- 9534547
TI  - It's no accident ... it's preventable.

PMID- 9534548
TI  - An adult man with a wound to the foot.

PMID- 9534549
TI  - Flooding in the Red River Valley: challenges met by the Grand Forks emergency
      medical services community.

PMID- 9534550
TI  - Mary's wishes.

PMID- 9534551
TI  - When nurses stations are empty.

PMID- 9534552
TI  - The art of nursing: a concept analysis.
AB  - That nursing is a science and an art is commonly accepted. While much emphasis
      has been placed on the science in nursing, the art of nursing is less well
      understood. A concept analysis using Rodgers' evolutionary perspective was
      conducted to examine the meaning of the art of nursing. Through the analysis, a
      definition emerged suggesting that the art of nursing is the intentional creative
      use of oneself, based upon skill and expertise, to transmit emotion and meaning
      to another. It is a process that is subjective and requires interpretation,
      sensitivity, imagination, and active participation.

PMID- 9534553
TI  - Use of writing portfolios for interdisciplinary assessment of critical thinking
      outcomes of nursing students.
AB  - This article discusses an interdisciplinary research project in which faculty
      from nursing and english collaborated in the assessment of students' critical
      thinking skills as reflected in writing portfolios. Faculty reviewed students'
      writing portfolios and then corresponded on email from two different universities
      about evidence of critical thinking in the portfolios. Findings suggest that
      writing portfolios can provide important evidence of critical thinking outcomes.
      To do this, however, faculty need to design writing assignments to foster
      critical thinking skills, helping students to think not only about learning to
      write, but also about using writing to learn.

PMID- 9534554
TI  - Healthcare rationing: issues and implications.
AB  - What methods, if any, should be used to practice healthcare rationing? This
      article looks at healthcare rationing in the United States, identifies ethical
      issues associated with implementing healthcare rationing, and addresses legal
      implications. The author utilizes sources from published literature and her own
      experience. Society must recognize that it does not have the resources available
      to fulfill all healthcare needs of all its members. Resolution will bring
      conflict and compromise.

PMID- 9534555
TI  - Involving families in the production of patient information literature.
AB  - Many information booklets are written by health-care staff and may not address
      patients' needs. Collaboration between patients and staff in the production of
      patient information can improve patient understanding and empower the patient and
      family to take an active part in treatment.

PMID- 9534556
TI  - Establishing ambulatory chemotherapy at home.
AB  - The use of infusional ambulatory chemotherapy is increasing. Careful patient
      selection and a structured programme of teaching and home support is required.
      Continuous ambulatory chemotherapy can improve clinical outcomes and provide both
      psychological and financial benefits.

PMID- 9534557
TI  - Evaluating two dressings for the prevention of nasal bridge pressure sores.
AB  - Nasal intermittent positive pressure ventilation (NIPPV) can provide symptom
      control and improved quality of life for patients with acute and chronic
      respiratory failure. Many patients using a Respironics mask for NIPPV develop
      nasal bridge pressure sores. Two dressing were compared for effectiveness in
      preventing such sores. Patients using Granuflex had less skin deterioration over
      time compared to a comparison group and patients using Spenco Dermal.

PMID- 9534558
TI  - Performing diagnostic skin biopsies.
AB  - The Scope of Professional Practice states that nurses may respond to the needs of
      patients by expanding their practice. Performing skin biopsies for cancer
      diagnosis is one such area. The provision of appropriate education, training and
      updating is essential. Clear guidelines for practice are required for all such
      procedures.

PMID- 9534559
TI  - Endotracheal suction.
AB  - Patients with a tracheostomy will need regular endotracheal suction to remove
      secretions from the tracheobronchial tree. This Update discusses the
      complications that can arise, including tracheal infection and mucosal trauma.

PMID- 9534560
TI  - Surgical excision of a pharyngeal pouch.
AB  - A pharyngeal pouch usually occurs in people over 70. This Update examines
      symptoms, management, surgical treatment and the postoperative care of patients,
      focusing on nutrition, care of the nasogastric tube and mouth care.

PMID- 9534561
TI  - Specialist nurses.

PMID- 9534562
TI  - Dynamic systems for pressure sore prevention.
AB  - Dynamic support systems are designed for the prevention and management of
      pressure sores in medium- to very-high-risk patients. Careful patient assessment
      is required for the effective use of these support systems. The selected product
      must be comfortable and acceptable to the patient.

PMID- 9534563
TI  - On the right course.

PMID- 9534564
TI  - The aetiology of malnutrition in hospital.
AB  - Malnutrition is a largely unrecognised problem in hospitals. Older people, people
      with cancer, respiratory disease and gastrointestinal problems are particularly
      vulnerable.

PMID- 9534565
TI  - Nutritional screening and assessment.
AB  - Health professionals need to take part in nutritional screening and assessment.
      Nutritional screening tools must meet criteria for reliability and validity. A
      number of assessment techniques can be used to establish nutritional status.
      Effective interdisciplinary working can improve outcome.

PMID- 9534566
TI  - [Primary health care, specialized health care--quality of nurses' reports].
AB  - This retrospective study on nurses' reports is based on data from case records
      upon release of patients from hospital care during the months of May, June and
      July 1994. The 373 reports evaluated according to defined criteria demonstrated
      that nurses filled out their reports in a very acceptable manner. Among the
      observations made, these stand out: 99% of the reports were legible; 97%
      appraised the patient's necessities; 83% included the name and signature of the
      nurse; and 90% prescribed patient's health problems, 75% of which were defined as
      nurses' diagnoses. The high degree by which nurses filled out their reports
      according to these set criteria led hospital personnel to be able to locate
      patients quickly, know their basic necessities and provide insight into, or a
      proposal for, appropriate nursing care.

PMID- 9534567
TI  - [AIDS: nursing care, new perspectives].
AB  - OBJECTIVES: To revise the recent changes which have occurred in the diagnosis of,
      clinical stay for, and treatment of AIDS and their repercussions in nursing care.
      1997 was characterized by the clear dominance of new advances in combined therapy
      using antiretorvirus drugs, by the possibility to measure the degree and number
      of the virus infection, and an improved knowledge of the dynamics and variability
      of the AIDS virus. Infected persons' quality of life can benefit from nursing
      care to check the gradual physical, cognitive and emotional deterioration
      patients continue to suffer from, in spite of the tenuous hope which new
      scientific discoveries and advances have introduced and which are very slowly
      becoming a part of treatment programs. SOURCES FOR THIS STUDY INCLUDE: MEDLINE
      data base studies published between 1990 and 1996, regular "SEISIDA"
      publications; summaries from the XIth International AIDS Conference held in
      Vancouver in July 1996; reports published by the Centers for the Control and
      Prevention of Diseases (CDC); and articles published or pending publication
      written by the authors. ARTICLE SELECTION: Selection of original articles
      published from 1990 to 1996 on the MEDLINE data base dealing with nursing
      treatment for patients infected by HIV in hospital, community center or homecare
      service units.

PMID- 9534568
TI  - [The Albacete University Nursing School. Interview with Elias Rovira Gil,
      Director of the Albacete school].

PMID- 9534569
TI  - [Surgery on the crystalline lens. A plan of standardized care].
AB  - In these days of concern for the growing costs of medical care it is an opportune
      moment to promote the importance of nurses as health care professionals and the
      roles that they play. This article presents a structural care plan for specific
      clinical situations regarding lens surgery with the goal of both guaranteeing
      quality nursing care and a method to evaluate costs. Lens surgery, a equently
      performed operation in the hospital, is used as an example to evaluate criteria
      of adequate service and efficiency. This method is based upon L.J. Caronito s
      bifocal model of clinical nursing.

PMID- 9534570
TI  - [Sexuality in neurological patients. The nurse's intervention].
AB  - Dealing with neurological patients' sexual problems is a task which nurses can
      not forget and treat lightly or not at all. After a brief resume of the
      biological and physical factors involved in controlling the nervous system in
      regards to sexuality, as well as recent epidemiological studies about sexual
      disfunction in the neurological patient, we propose a model for nurses to follow.
      The objectives of this model are to serve as a nursing guide and to stimulate
      future research on the nurse's role in sexuality.

PMID- 9534571
TI  - [Left half of the mandible. (Lateral and medial aspects)].

PMID- 9534572
TI  - [Ribavirin administration by aerosol].
AB  - This article presents the recommended procedures to administer ribavirin by means
      of an aerosol as followed at the Maternity-Childcare University Hospital in Vall
      d'Hebron, Barcelona. Ribavirin is a wide spectrum anitviral drug applied by
      aerosol means against severe infections caused by the respiratory syncytial
      virus. Said administering technique is complex and requires a considerable degree
      of nursing care, knowledge regarding its correct use, and hospital care. Bear in
      mind that careless administration of this drug can cause illness in the nurses
      who apply it. Therefore, it is necessary to follow the correct procedures
      described in this article.

PMID- 9534573
TI  - [Alert! We are responsible for the health of our spine].
AB  - The author stresses the importance of keeping our spine in good shape, both for
      our physical welfare as for our socio-economic. To this end, this article starts
      off with a study of the spine and an analysis of the basic principles of body
      mechanics. Next, the author points out exercise as the fundamental therapeutic
      factor for alleviating back pain. She describes some of the most common exercises
      recommended to alleviate back pain as well as a few practical suggestions for
      daily activities. If followed, one will be on one's way to a correct posture
      which will better the health of one's spine.

PMID- 9534575
TI  - [The role of psychiatric hospitals].

PMID- 9534574
TI  - [Political dynamics for the reduction in institutionalization in Quebec].

PMID- 9534576
TI  - [Status of psychiatric hospitals in the United States in 1996].
AB  - OBJECTIVES: This analytical review is intended to update the author's earlier
      writings on the position of the state mental hospital within the spectrum of
      services for long-term mental patients and to provide a perspective for the next
      generation of service planners. METHODS: Findings and commentary are organized
      around four major questions. First, what is the prevailing view of state mental
      hospitals today, and how does it compare with the view that existed in the first
      half of this century? Second, what individuals tend to be served in state mental
      hospitals today? Third, what has been the fate of mentally ill persons who are no
      longer served in state mental hospitals? Fourth, what is an appropriate role for
      the state mental hospital in today's uncertain and rapidly changing systems of
      care? RESULTS AND CONCLUSIONS: Individual state mental hospitals vary in the
      composition of their resident populations, the content of their services, and the
      overall quality of their care. Although they have been superseded by community
      based service structures in some places, they continue in general, as the result
      of their multifunctionality, to occupy a critical place in systems of care.
      Renewed efforts to integrate them as full partners within those systems must be
      undertaken.

PMID- 9534577
TI  - [The future of psychiatric hospitals in Ontario].
AB  - The purpose of this paper is to review past and present roles and to speculate on
      the future of the Ontario provincial psychiatric hospitals (PPHs). Currently, and
      for the very immediate future only, there are 10 PPHs that are owned and operated
      by the Ministry of Health of Ontario, each serving a specified population ranging
      from 250,000 to over 3,000,000. In addition to clinical expertise, provincial
      psychiatric hospitals contribute greatly to teaching and research. Ontario's
      mental health reform movement has called for a shift of resources to the
      community and a downsizing of PPHs by 2003. In response to fiscal pressures, in
      1996 provincial legislation was passed to establish the Health Services
      Restructuring Commission (HSRC) as a stand-alone corporation with powers to
      restructure and reengineer health services in Ontario. The HSRC has to date
      recommended the closure of 4 PPHs by 1999 and the integration of theses services
      into other medical facilities. While a rebalancing of the mental health system
      does need to take place, the fiscally driven haste to close hospitals has created
      a crisis atmosphere in PPHs for staff and patients. It is also unlikely that the
      necessary community resources will be in place to buffer these changes. The new
      restructuring plans not only set unrealistic timelines, they seem to
      underestimate the importance PPHs have played in teaching, research and the
      advancement of clinical treatment and rehabilitation of the severely mentally
      ill. It may be that, in the long run, service integration and divestment/closure
      of the PPHs will result in better access to services closer to smaller
      communities and in the destigmatization of the mentally ill, however, without
      close evaluative monitoring and appropriate leadership, it could also lead to
      decreased research, training and quality of care.

PMID- 9534578
TI  - [The Italian reform, 18 years after: history, execution and consequences].
AB  - In 1978 a radical psychiatric reform was passed in Italy, that revolutionized the
      mental health delivery system. The reform has attracted international attention
      for its resolute commitment to getting rid of the traditional state hospital and
      implementing a nationwide mental health system without this type of hospital. The
      paper begins by depicting its preparation, then after charting the main features
      of the reform and its implications, it moves on to providing data on the
      implementation. In the following years relevant legislation has supplemented the
      reform and is covered in the paper. Other concurrent elements of the
      implementation process are mentioned and existing empirical studies reviewed.

PMID- 9534579
TI  - [The statute of deinstitutionalization in Great Britain].
AB  - The aim of this article is to explain the current status of
      deinstitutionalisation and of community care development by studying the extent
      to which community care can or should take over the functions of the asylum.
      These functions include those that are manifest, or explicit, and those that are
      latent, or unintended but implicit (Bachrach 1976). The continuing relevance of
      both sets of functions is argued to be exerting a powerful influence on the
      processes of asylum closure and community care development. The results include
      delayed asylum closures and transinstitutionnalisation, the shift of some
      patients from asylums to other institutions, which stifle the development of
      community care by concentrating spending in hospitals.

PMID- 9534580
TI  - [Characteristics of the populations at the Robert Giffard Psychiatric Hospital
      Center: people with intellectual deficiencies and people with mental disorders].
AB  - Within the context of the general reorganization of health care and social
      services in Quebec, the present study aims at describing physical and mental
      characteristics of persons with mental health problems and who are mentally
      retarded still hospitalized in a psychiatric hospital. In the first study, 146
      mentally retarded persons of which 74 formed the community group and 72 the
      institutionalized group. The results indicate that 84% of the mentally retarded
      persons still hospitalized manifested sufficiently important needs on the three
      measured variables (health, deficits and behaviors) to justify intensive care in
      a structured environment. The Behavior variable is more important in deciding the
      integration of these people in the community. As most of these persons have a
      higher level of disabilities and more behavior manifestations, the support
      required for these people in the community and persons delivering services will
      have to be more structured and intensive in nature. In the second study, 928
      psychiatric patients still hospitalized were studied on the variables, age, sex,
      diagnostics and the global scores (physical and mental) of the level of care
      survey and functional autonomy. The results show that the proportion of women in
      the age group 35 and older were progressively increasing in relation to the men.
      The primary diagnostic reported more frequently was schizophrenia in 70% of
      cases. In the evaluation of physical care of the people still hospitalized, age
      becomes an important factor. Generally speaking, the population within the
      institution is aging and women are progressively growing in number. As these
      people expressed more physical ailments and a decline in basic autonomy, more
      structured and specialized care and support will be required to respond to their
      needs.

PMID- 9534581
TI  - [The rehabilitation of the psychiatric hospital. A question of audacity and
      synergy].
AB  - Using a mode of psychodynamic analysis, this article exposes some similarities
      between the factors that hinder the social reintegration of the "patient" and the
      social and political forces opposing the "rehabilitation" of the social
      institution represented by the psychiatric hospital. In support to this analogy,
      the article outlines the transformations realized over the last few years at the
      Centre hospitalier psychiatrique Sainte-Therese of Shawinigan and suggests that,
      in order to make such changes, the development of rehabilitation services can
      serve as a catalyst. The authors also propose a perceptual analysis of human,
      political and social reactions created by the metamorphosis of the traditional
      role attributed to the psychiatric hospital.

PMID- 9534582
TI  - [The creation of partnerships: perspectives and possibilities].
AB  - This article re-examines access to treatment and care in the current context of
      fiscal restriction and change in locus of care. Taking the position that the
      development of partnerships with all parties who work in the mental health area
      is an important process, this article argues that such processes are infrequently
      discussed. Further, creating a partnered relationship with the person with mental
      disorder is also neglected. The authors examine mechanisms of relationship change
      as care moved from large, total-care institutions to general hospitals and
      finally, to the community. How professionals, individuals with mental disorder
      and their families have been affected by this change in terms of how alliances
      are constituted and maintained is discussed. The authors conclude with two case
      examples which illustrate the reconciliation and non-reconciliation of differing
      points of view between all partners which likely affected clinical outcomes.

PMID- 9534583
TI  - [Lessons in transferring resources: the system of fees per patient].
AB  - Dowries can be defined as lump sum payments or continuing grants which health
      authorities make between themselves and to local authorities or voluntary
      organisations in respect of people with severe mental disorders to be cared for
      in the community instead of in hospital. This paper has three aims. First to
      describe how dowries and other processes were set up to encourage the closure of
      two psychiatric hospitals in England. The broader financing context for mental
      health care (prior to the reforms in England engendered by the NHS and Community
      Care Act, 1990) is also described and shows some similarities to the current
      arrangements in Quebec. Second, we abstract some information from a long-running
      evaluation of the reprovision programme to look at the type of services used in
      the community by former long-stay patients of these two hospitals and the
      comparative costs of hospital and community-based care. After leaving hospital,
      former patients require considerable inputs from other health and social care
      services; any development of community care for these patients should at the
      least mirror the facilities provided on the hospital campus. The final aim of
      this paper is to examine the extent to which this English system of budget
      reallocation ("dowries") can be employed in Quebec to further reduce long-stay
      hospital provision. There are many similarities between the health and social
      care systems of the two countries but there are also organisational and political
      differences. It is not sensible, therefore, to transfer the English budget
      reallocation to Quebec wholesale, but we suggest that there are important process
      and implementation issues which can guide the development of financing mechanisms
      in Quebec.

PMID- 9534584
TI  - [Validation of Satisfaction with Life Domains Scale in Quebec].
AB  - This article presents the results of the Quebec validation of the Satisfaction
      With Life Domains Scale: This scale was developed in the United States for the
      general population and adapted for severely mentally ill individuals. Two hundred
      and sixty six individuals from the general population and 245 severely mentally
      ill persons participated in this study. Factor analysis allowed the
      identification of four sub-scales for the clinical population and five for the
      general population. The scale (alpha = 0.90) and the sub-scales (alpha between
      0.60 et 0.84) show excellent internal consistencies and the test-retest
      reliability was good (r = 0.73). Moreover, analysis of the variance and the
      discriminant analysis allow to acknowledge that the sub-scales have a high
      discriminating power; they allow to distinguish the general population from
      welfare recipient and people suffering from psychosis. The overall results
      suggest that l'Echelle de satisfaction des domaines de vie have good psychometric
      properties and can be considered as a valid instrument for assessing subjective
      quality of life in descriptive or evaluative studies.

PMID- 9534585
TI  - [Drugs and criminal issues: assessment of research in Quebec].
AB  - Although research on the link between drugs and crime is not a major concern for
      many Quebec researchers, the last five years have been the scene of an increasing
      number of studies on the subject. These studies can be divided in four groups: 1)
      criminal policies; 2) studies on prevalence; 3) relation between drugs and crime;
      4) intervention and its impact. Results of these studies put additional pressure
      for adequate treatment of addicts having problems with the law. Social workers in
      rehabilitation centres have thus noticed an increasing number of addicts who had
      or were going through problems with the law. Yet a great proportion of addicts
      having problems with the justice system are not reached by rehabilitation
      services: it is those people who present the most deteriorated bio-social
      profile. Is it really worthwhile to intervene with this type of clientele? The
      answer is yes as long they can be kept in treatment sufficiently long. In any
      case, the simple judiciarization of a person says nothing of his character (e.g.
      violent, liar or fraudulent) or of his pathology (e.g. psychopath, sociopath
      ...). In fact, given the illicit nature of certain drugs, the simple fact of
      using can lead to criminalization. The challenge in research in this field will
      consist in better defining factors related to perseverance in treatment and
      therapeutic ingredients associated to the desired impact.

PMID- 9534586
TI  - [Relevance of the stress-coping paradigm in the elaboration of a stress
      management model for schizophrenics].
AB  - Studies having used the stress-vulnerability model of schizophrenia as a
      conceptual framework demonstrate from different perspectives the contribution of
      stress when symptoms and deteriorations associated with this illness appear. The
      stress-coping paradigm provides an explanation of the effects of stress on health
      according to a contextual approach underlining how the coping process allows to
      diminish the negative effects of stress and favour adaptation in difficult or
      conflicting situations. This article proposes the integration of these two
      dominant currents and presents the Stress management model for schizophrenics.
      This new model provides the opportunity to favour the comprehension of the
      process of rehabilitation for schizophrenics and the development of new methods
      of intervention in rehabilitation.

PMID- 9534587
TI  - [Validation of a model of psychosocial determinants of occupational health of
      geriatric nurses].
AB  - The purpose of this study was to verify a model of relationships between
      psychosocial factors and health for 8066 francophone nurses working in geriatric
      care in Quebec. A random sample of 1990 subjects was drawn and a participation
      rate of 77.9% and 55% was obtained for the two-time study taken twelve months
      apart. Based on the theory of Maddi and Kobasa (1984), the model was reproduced
      for the two-time periods with the aid of structural equations. The analyses
      showed that three variables exert a direct influence on psychological distress:
      professional burnout, occupational stressors and hardiness. Also, variables have
      a direct effect on burnout: listed in order of importance, these are hardiness,
      occupational stressors, work support, active strategies of coping and employment
      status. In dealing with the work stressors, the nurses who are hardy make use of
      active strategies of coping and look for support form their colleagues. The
      results of the study help to better understand the psychological and social
      resources that best favor adaptation of working women in highly demanding work
      environments. The fallout of the study converges towards the quality of life of
      helping professionals and towards the cost and quality of health and social
      services.

PMID- 9534588
TI  - [Therapeutic impasse].

PMID- 9534589
TI  - [Violence in general and psychiatric emergency units].

PMID- 9534590
TI  - [Stakes in ethics and the underlying ethics in the debate about reform of health
      services and social services in Quebec].

PMID- 9534592
TI  - [Professional reading and writing].

PMID- 9534591
TI  - [Sexual exploitation of patients: zero tolerance].

PMID- 9534593
TI  - [A documentation center. A place for culture, research and exchanges].

PMID- 9534594
TI  - [About the thesaurus...].

PMID- 9534595
TI  - [How to select your reading].

PMID- 9534596
TI  - [Association of Documentation Specialist in Nursing Education].

PMID- 9534597
TI  - [Documentation mission].

PMID- 9534598
TI  - [Computerizing a documentation center].

PMID- 9534599
TI  - [Information and education].

PMID- 9534600
TI  - [The rules of bibliographic presentation].

PMID- 9534601
TI  - [Information and documentation in the health field].

PMID- 9534602
TI  - [Education and the multimedia. Reflections on European programs].

PMID- 9534603
TI  - [Orders and professions: a delicate genealogical problem].

PMID- 9534604
TI  - [Nursing education. A professional project and its changing possibilities].

PMID- 9534605
TI  - [The teacher and evaluation].

PMID- 9534606
TI  - [Expertise and change].

PMID- 9534607
TI  - [The test of putting to work the State Nursing Diploma].

PMID- 9534608
TI  - [Nurses, structures, society. What changes will come to the district?].

PMID- 9534609
TI  - [Prehistory and history: continuity and breaks. From solitary confinement to
      asylum to clinical psychiatry unit].

PMID- 9534610
TI  - [Geo-demographic aspects of the district].

PMID- 9534611
TI  - [Defense and description of district psychiatry].

PMID- 9534612
TI  - [Liaison psychiatry].

PMID- 9534613
TI  - [Options of care and practice in the district].

PMID- 9534614
TI  - [Commentary on a nursing practice].

PMID- 9534615
TI  - [Competence and harmony].

PMID- 9534616
TI  - [Criminology and the nurses part].

PMID- 9534617
TI  - [Organizing a medical psychological reception center].

PMID- 9534618
TI  - [Child psychiatry and adolescent psychiatry. Nursing care].

PMID- 9534619
TI  - [Unusual aggression].

PMID- 9534620
TI  - [Plans for nursing are being developed internationally too. With the ICN towards
      2000].

PMID- 9534621
TI  - [Nurses can help fulfill wishes of terminal residents. Dying in the nursing
      home].

PMID- 9534622
TI  - ['Care renewal? New cares, you mean!'. Interview by Jan van Deursen].

PMID- 9534623
TI  - [Nurses ensure the care for children of mentally ill parents. Children and the
      parent role of the patient].

PMID- 9534624
TI  - [Self determination under pressure in mentally ill patients. Decreased capability
      for autonomy].

PMID- 9534625
TI  - [Diagnosis in nursing--individually or in team context].

PMID- 9534626
TI  - [Practice and science].

PMID- 9534627
TI  - [Practice and science].

PMID- 9534628
TI  - [We should be more business-like].

PMID- 9534629
TI  - Anaesthesia for caesarean section in patients with aortic stenosis: the case for
      regional anaesthesia.

PMID- 9534630
TI  - Anaesthesia for caesarean section in patients with aortic stenosis: the case for
      general anaesthesia.

PMID- 9534631
TI  - Intensive care services; a crisis of increasing expressed demand.
AB  - Critical care services appear to face increasing demand. To attempt to identify
      factors which may predispose to such increases in demand, the patients and their
      treatment were reviewed. The patients' ages, referring specialty and their risk
      of hospital mortality were recorded on admission. The durations of respiratory
      and renal support (if required) were recorded. Pulmonary artery catheter
      insertion and the number of vasoactive drugs infused were also noted. During the
      study, the capacity of the intensive care unit was initially increased by one bed
      (from six to seven) and later by a six-bedded high-dependency unit. This capacity
      increase was not matched by a proportionate decrease in occupancy. The patients'
      mean ages increased by 1 year per year. The number of patients referred from
      general surgery consistently increased. The proportion of patients receiving
      vasoactive drugs and pulmonary artery catheters declined as did the duration of
      respiratory and renal support.

PMID- 9534632
TI  - Quantifying meaningful changes in pain.
AB  - One hundred and thirty-eight nurses were asked to indicate the smallest
      meaningful reduction in pain from each of four hypothetical pain intensities:
      100, 75, 50 and 25, on 100 mm visual analogue scales. The median values for the
      smallest meaningful reductions in pain were 31, 24, 18 and 10 mm, respectively,
      representing reductions in pain intensity of 31%, 32%, 36% and 40%, respectively.
      These tests were repeated in 110 patients before and after they had a lower third
      molar extraction under general anaesthesia. The patients' expectations of pain
      relief, pre- and postoperatively, were very similar to those observed in the
      nurses. For each of the four hypothetical pain intensities the median values for
      meaningful reductions in pain became greater following surgery. The pre-operative
      median reductions from the hypothetical pains 100, 75, 50 and 25 mm were 26, 20,
      15 and 11 mm (26%, 27%, 29% and 44%), respectively. The corresponding
      postoperative reductions were 31, 24, 19 and 12 mm (31%, 32%, 38% and 48%). To
      achieve a meaningful reduction in pain postoperatively in 50% of patients it is
      necessary to reduce pain as represented by the visual analogue scale, by between
      31 and 48%, depending on its initial intensity.

PMID- 9534633
TI  - Timing of removal of the laryngeal mask airway.
AB  - Previous studies reported that complications associated with removal of the
      laryngeal mask were more frequent in awake patients than in anaesthetised
      patients; however, these studies did not comply with the method described in the
      manufacturer's instruction manual. The reported incidences of regurgitation
      during the use of the laryngeal mask also differ considerably between studies. We
      studied these factors in 66 patients in whom the method described in the manual
      was used. After induction of anaesthesia, the laryngeal mask and a pH probe were
      inserted and the cuff of the mask was inflated with a minimum volume of air.
      Anaesthesia was maintained with nitrous oxide and isoflurane in oxygen. At the
      end of the operation, we randomly allocated patients to one of two groups and the
      laryngeal mask was removed either while they were still deeply anaesthetised or
      after they had regained consciousness. No apparent regurgitation occurred in any
      patient during operation, but one patient in the anaesthetised group regurgitated
      immediately after removal of the mask. The incidence of complications during or
      after removal of the laryngeal mask was significantly greater in the
      anaesthetised group than that in the awake group (p << 0.001; difference [95%
      CI]: 48.5 [30.5-66.5]%). Therefore, the laryngeal mask can be safely left in
      place until the patient has regained consciousness after emergence from
      anaesthesia.

PMID- 9534634
TI  - Reporting of 'hypotension' after epidural analgesia during labour. Effect of
      choice of arm and timing of baseline readings.
AB  - We studied 20 women in labour to see how reporting 'hypotension' after obstetric
      epidural analgesia is affected by position of the blood pressure cuff and
      baseline definition. Blood pressure was recorded from both arms simultaneously
      while the woman was semirecumbent and then in the left lateral position. Three
      readings were then taken after epidural bupivacaine, one left lateral and the
      remainder right lateral. Before the epidural, blood pressure in the dependent arm
      in the lateral position was similar to blood pressure in either arm in the
      semirecumbent position and an average of 10 mmHg (systolic) and 14 mmHg
      (diastolic) higher than blood pressure in the uppermost arm (p < or = 0.00005).
      This difference persisted in both lateral positions as epidural analgesia became
      established. Choosing different definitions of hypotension, baselines and arm to
      measure blood pressure resulted in 'hypotension rates' between 0% and 75%. For
      blood pressure measurement in the lateral position, the blood pressure cuff
      should be placed on the dependent arm.

PMID- 9534635
TI  - A portable self-learning fuzzy logic control system for muscle relaxation.
AB  - We have assessed the practicality and performance of the Vital Signs Paragraph
      neuromuscular blockade monitor as part of a 'self-learning' fuzzy logic control
      feedback system used to administer atracurium to a required depth of
      neuromuscular blockade. Fifteen patients undergoing surgery expected to last
      longer than 90 min entered the study. A Vital Signs Paragraph was used to measure
      the degree of neuromuscular blockade and control it such that the first twitch of
      the train-of-four was kept at 10% of its baseline value. The controller
      instructed a Graseby Medical 3400 infusion pump to administer an atracurium
      infusion to maintain this level of blockade. Five patients (33%) were withdrawn
      from the study due to inadequate piezo-electric sensor function. In the remaining
      10 patients, the system achieved stable control of neuromuscular blockade with a
      mean (range) error for the first twitch of the train-of-four of -0.45 (-1.06 to
      0.13)%. The mean atracurium infusion rate ranged from 0.13 to 0.67 mg.kg-1.h-1.
      These results compare reasonably well with previous results using the Datex
      Relaxograph, whilst the system itself was portable and easy to use. However, the
      reliability of the system was limited due to variability in the sensitivity of
      piezoelectric sensors.

PMID- 9534636
TI  - Neuromuscular interactions between mivacurium and esmolol in rabbits.
AB  - We compared the dose-response relationship and the neuromuscular blocking effects
      of mivacurium during infusions of esmolol in 40 anaesthetised rabbits. Train-of
      four stimuli were applied every 10 s to the common peroneal nerve and the force
      of contraction of the tibialis anterior muscle was measured. Plasma
      cholinesterase activity decreased by 13% after esmolol infusion. The ED95 of
      mivacurium increased significantly from 29 (4.8) micrograms.kg-1 with placebo to
      61 (9.8) micrograms.kg-1 during esmolol 100 micrograms.kg-1.min-1, 49 (8.2)
      micrograms.kg-1 during esmolol 300 micrograms.kg-1.min-1 and 54 (7.3)
      micrograms.kg-1 during esmolol 500 micrograms.kg-1.min-1, respectively (p <
      0.001). The duration of neuromuscular block with mivacurium 0.16 mg.kg-1 was
      prolonged by 30% with esmolol due to diminished plasma cholinesterase activity (p
      < 0.05). Heart rate and mean arterial blood pressure decreased by 15% with
      esmolol (p < 0.05). The results of this study show that, in rabbits, esmolol
      decreased plasma cholinesterase activity, antagonised the neuromuscular blocking
      potency of mivacurium and prolonged its neuromuscular blocking effect.

PMID- 9534637
TI  - The influence of neck position on ventilation using the Combitube airway.
AB  - A Combitube airway was inserted into 40 patients undergoing general anaesthesia.
      A rigid cervical collar was then used to immobilise the neck of each patient. In
      all 40 subjects adequate ventilation of the lungs was possible in this position
      as assessed by chest movement and auscultation, measurement of expired tidal
      volume and maintenance of satisfactory arterial oxygen saturation. In 18/40
      patients (45%), blood was present on the Combitube after removal. Reducing the
      volume of air injected into the proximal balloon of the Combitube appeared to
      reduce the incidence of airway trauma during insertion.

PMID- 9534638
TI  - Effect of orifice-area reduction on flow characteristics during injection through
      spinal needles.
AB  - A reduction in hole size for certain side-port spinal needles has been advocated
      in recent reports. While the influence of orifice-area reduction on the
      aspiration capability of the needle has been studied, the influence on the
      anaesthetic delivery properties is relatively unknown. As a first step in
      understanding the effects of hole-size reduction on anaesthetic distribution
      within the subarachnoid space, we studied flows emanating from isolated needles
      using computer simulations. Following validation of the numerical model using
      experimental particle visualisation, trajectories of anaesthetic particles
      injected through 25 G Whitacre needles of various orifice areas were computed and
      used to determine the orientation and rate of spread of the anaesthetic jet
      exiting the needle. Two factors impacting the concentration distribution were
      observed: the rate of spread of the anaesthetic jet increases markedly with
      decreasing orifice area and the jet alignment shifts toward perpendicular to the
      needle axis.

PMID- 9534639
TI  - The aetiology and prevention of peri-operative corneal abrasions.
AB  - Corneal abrasion is the most frequent ocular complication to occur during the
      peri-operative period. This review describes the aetiology of corneal abrasions
      and evaluates the current methods of prevention. Most abrasions are caused by
      lagophthalmos (failure of the eyelids to close fully) during general anaesthesia,
      resulting in corneal drying. General anaesthesia reduces both the production and
      the stability of tears and therefore increases the incidence of this painful
      condition. Taping the eyelids closed, soft contact lenses, the instillation of
      aqueous gels or paraffin-based ointments are all effective in preventing corneal
      abrasions, but ointments are associated with significant morbidity.

PMID- 9534640
TI  - Dutch case-control study of anaesthesia-related morbidity and mortality.
      Rationale and methods.
AB  - To date, anaesthesia-related mortality, morbidity and risk factors have almost
      exclusively been studied qualitatively rather than quantitatively. Therefore,
      knowledge of the relative risk associated with many anaesthesia-related factors
      is still lacking. Recently, a quantitative study of the determinants and
      prevention of morbidity and mortality in anaesthesia was started in the
      Netherlands. Its objective is to study severe peri-operative morbidity and
      mortality as a function of anaesthesia-related risk factors. The study is
      designed as a case-control study within a prospectively defined cohort. The
      cohort comprises all patients undergoing an anaesthetic procedure, either
      general, regional or a combination, in one of 61 hospitals between 1 January 1995
      and 1 January 1997. A 'case' is a patient who dies within 24 h of undergoing an
      anaesthetic procedure or who remains comatose 24 h after an anaesthetic
      procedure. A 'control' patient is a randomly chosen patient who has undergone
      anaesthesia and is matched for gender and age. The present report discusses the
      study protocol.

PMID- 9534641
TI  - Regional anaesthesia with a subarachnoid microcatheter for caesarean section in a
      parturient with aortic stenosis.
AB  - We present a woman in her first pregnancy, with known aortic stenosis prior to
      conception, who successfully underwent regional anaesthesia for an elective
      Caesarean section using a subarachnoid microcatheter. The anaesthetic management
      of patients with aortic stenosis requiring noncardiac surgery is a complex and
      contentious matter, particularly when the situation is compounded by the
      physiological changes accompanying pregnancy and delivery. This is the first
      reported use of a subarachnoid microcatheter in such a patient. The choice of
      technique is discussed and compared with other options for providing anaesthesia.

PMID- 9534642
TI  - Rescue from neutropenic fever and a bamboo pole.
AB  - We describe a patient admitted to the intensive care unit following a penetrating
      head injury. This patient developed agranulocytosis and subsequently pancytopenia
      secondary to an idiosyncratic drug reaction. The possible causative drugs are
      phenytoin, cloxacillin, ceftriaxone and ceftazidime. The patient was treated with
      recombinant human granulocyte colony-stimulating factor.

PMID- 9534643
TI  - Requirements for muscle relaxation in Friedreich's ataxia.
AB  - Friedreich's ataxia is an inherited disorder of the nervous system, requiring
      special care during anaesthesia, because of increased sensitivity to muscle
      relaxants. We report a case of Friedreich's ataxia in a 31-year-old woman,
      anaesthetised on two occasions, for tendinoplasty and pes cavus repair.
      Atracurium was used for neuromuscular blockade and monitored by a train-of-four
      twitch technique. The patient's response was normal. She returned to adequate
      spontaneous breathing within 20 min of the last dose of the muscle relaxant
      without need for anticholinesterase administration. When neuromuscular function
      is monitored, normal doses of muscle relaxant can safely be used in these
      patients.

PMID- 9534644
TI  - Blood transfusion facilitating difficult weaning from the ventilator.
AB  - We report a case series of five anaemic patients (haemoglobin: 8.7 +/- 0.8 g.dl
      1) with chronic obstructive lung disease in whom trials of weaning from the
      ventilator were unsuccessful. After transfer to our regional weaning centre,
      blood was transfused to increase the haemoglobin value to 12 g.dl-1 or higher.
      Subsequently, all patients were weaned successfully. We conclude from our
      experience that in anaemic patients with chronic obstructive lung disease there
      should not be a fixed transfusion threshold. In anaemic patients in whom
      difficulty in weaning from the ventilator is experienced, blood transfusion
      should be tailored to the individual patient's needs. Transfusion in those with
      chronic obstructive airways disease may lead to successful weaning.

PMID- 9534645
TI  - Bilateral lingual nerve injury following the use of the laryngeal mask airway.

PMID- 9534646
TI  - Cerebral infarct following central venous cannulation.
AB  - Inadvertent carotid artery puncture is a well-known complication of internal
      jugular vein cannulation. A case of cerebral infarct subsequent to carotid artery
      puncture during internal jugular vein cannulation is reported.

PMID- 9534647
TI  - How would patients prefer to spend the waiting time before their operations?
AB  - Many surgical patients are anxious while waiting to go to the operating theatre
      in spite of the best preparation with drugs, information and reassurance. It is
      possible that patients could be more comfortable if allowed a choice of
      activities before operations. The objective of this study was to find out how pre
      operative patients might prefer to occupy their time. We distributed 200
      questionnaires to elective surgery patients and 184 (92%) were available for
      analysis. Of the respondents, 54.1% wanted to be slightly sleepy, 72.0% preferred
      not to be fast asleep and 57.2% preferred not to be wide awake. Reading (56.8%),
      listening to music (57.1%) and chatting with other patients (39.9%) were
      preferred activities. It might be appropriate to ask patients how sedated they
      would wish to be before their surgery and perhaps have alternatives to sedation
      available.

PMID- 9534648
TI  - The effect of music on anaesthetists' psychomotor performance.
AB  - Music is frequently played in operating theatres, but may prove distracting to
      anaesthetists. We undertook a laboratory-based study of the effects of music on
      the psychomotor performance of 12 anaesthetic trainees. Using part of the
      computer-based PsychE psychomotor evaluation programme, we were unable to
      demonstrate any effect of self-chosen music, silence, white noise or classical
      music on their performance in these tests.

PMID- 9534649
TI  - A new gas jet method for the assessment of sensory block after spinal
      anaesthesia.
AB  - We evaluated a new method of assessing sensory block after spinal anaesthesia
      using a fine gas jet and compared it with other established methods. The gas jet
      method was used to test the block before and after surgery and was found to
      compare favourably with pin-prick (median difference 0 and 0 dermatomes) and
      ethyl chloride (median difference 0.5 and 1.0 dermatomes) but less well with
      cotton wool (median difference -2.0 and -2.0 dermatomes).

PMID- 9534650
TI  - Paediatric anaesthesia--who should do it?

PMID- 9534651
TI  - The McCoy laryngoscope.

PMID- 9534653
TI  - Use of a deflation tool before sterilisation of the laryngeal mask.

PMID- 9534654
TI  - Retrograde blind nasal intubation via the intubating laryngeal mask.

PMID- 9534652
TI  - Effect of jaw-thrust manoeuvre on the laryngeal inlet.

PMID- 9534655
TI  - Supervision: what is more important, quantity or quality?

PMID- 9534656
TI  - Caesarean section and respiratory failure.

PMID- 9534657
TI  - Confirmation of epidural catheter placement.

PMID- 9534658
TI  - Confirmation of epidural catheter placement.

PMID- 9534659
TI  - Use of a Seldinger wire to change a pulmonary artery catheter.

PMID- 9534660
TI  - Infusion disconnect alarms?

PMID- 9534662
TI  - Maintaining patency of central venous pressure lines.

PMID- 9534661
TI  - Age and opioid patient-controlled analgesia use.

PMID- 9534663
TI  - Helicobacter pylori.

PMID- 9534664
TI  - Checking block height prior to caesarean section.

PMID- 9534665
TI  - Anaesthetists and medical training.

PMID- 9534667
TI  - Benign childhood occipital seizures.

PMID- 9534666
TI  - Neonatal origins of schizophrenia.

PMID- 9534668
TI  - Gastrointestinal problems in the immunosuppressed patient.

PMID- 9534669
TI  - Heavy caffeine intake in pregnancy and sudden infant death syndrome. New Zealand
      Cot Death Study Group.
AB  - AIMS: To examine the association between maternal caffeine consumption during
      pregnancy and the risk of sudden infant death syndrome (SIDS). METHODS: A
      nationwide case-control study surveying parents of 393 SIDS victims and parents
      of 1592 control infants. Caffeine consumption in each of the first and third
      trimesters was estimated by questionnaire. Heavy caffeine intake was defined as
      400 mg/day or more (equivalent to four or more cups of coffee per day). RESULTS:
      Infants whose mothers had heavy caffeine consumption throughout their pregnancy
      had a significantly increased risk for SIDS (odds ratio 1.65; 95% confidence
      interval 1.15 to 2.35) after adjusting for likely confounding factors.
      CONCLUSION: Caffeine intake has been associated with fetal harm and now SIDS.
      Reducing heavy caffeine intake during pregnancy could be another way to lessen
      the risk of SIDS. This needs confirmation by others.

PMID- 9534670
TI  - The costs of early hearing screening in England and Wales.
AB  - A survey was carried out in 10 centres in England and Wales to determine the
      costs of hearing screening in the first year of life. The screens that were
      studied were targeted neonatal, universal neonatal, and the health visitor
      distraction test (HVDT) or alternative surveillance. Valid data were available
      from five centres for targeted neonatal screening (TNS), three for universal
      neonatal screening (UNS), and nine for the HVDT, although only five of the HVDT
      screens had valid data for follow up costs. The neonatal costs were consistent
      across the centres surveyed, whereas those for the HVDT screen varied
      considerably. The mean service costs for TNS, UNS, and the HVDT at 1994 prices
      were 5052 Pounds, 13,881 Pounds, and 24,519 Pounds for a standardised district of
      1000 live births. Three conclusions seem justified. Firstly, UNS need not be
      prohibitively expensive as it costs considerably less than HVDT screening.
      Secondly, TNS appears to be a relatively inexpensive way of improving the age of
      identification of a proportion of the congenitally hearing impaired. Thirdly,
      given the published yields for UNS and the HVDT, the results indicate that UNS
      offers the most cost effective overall approach with alternative systems in place
      to identify late onset permanent hearing losses.

PMID- 9534671
TI  - Disturbed sleep: effects of sociocultural factors and illness.
AB  - To assess the prevalence of sleep disturbance and associated risk factors, sleep
      patterns were analysed in 14,372 English and Scottish children. Approximately 4%
      of children aged 5 experienced disturbed sleep more than once a week, but this
      decreased to 1% from age 9. Less than 25% of the parents with an affected child
      consulted a doctor. Sleep disturbance was associated with persistent wheezing
      compared to non-wheezing children (odds ratio 4.42; 95% confidence interval (CI)
      3.17 to 6.13), and more frequent in children of Indian subcontinent descent than
      in white children (odds ratio 2.20; 95% CI 1.34 to 3.60), and in children whose
      mother reached no more than primary education compared with those with higher
      education (odds ratio 2.41; 95% CI 1.51 to 3.84). Sociocultural factors
      associated with ethnicity and respiratory illness are important risk factors for
      sleeping disorders in childhood.

PMID- 9534672
TI  - Cerebral oxygenation during cardiopulmonary bypass.
AB  - Cerebral fractional oxygen extraction (FOE) was monitored in 30 children, using
      near infrared spectroscopy during cardiopulmonary bypass, to investigate the
      effect of hypothermia and circulatory arrest. One group of children (n = 15)
      underwent profound hypothermia with total circulatory arrest (n = 8) or
      continuous flow (n = 7). Another group (n = 15), of whom only one had circulatory
      arrest, underwent mild (n = 6) or moderate (n = 9) hypothermia. The mean FOE (SD)
      before bypass was 0.35 (0.12) and this correlated negatively with the
      preoperative arterial oxygen content (r = -0.58). Between the stage of cooling on
      bypass and cold bypass there was a reduction in FOE in all groups. Between cold
      bypass and rewarming there was an increase in FOE only in the groups with
      continuous flow. In the circulatory arrest group, the FOE remained low during
      rewarming and was significantly lower than that of the continuous flow group. No
      patients died and none had neurological abnormalities postoperatively. Apparent
      changes in oxidised cytochrome oxidase concentration were also monitored using
      near infrared spectroscopy. There was a fall in cytochrome aa3 on starting
      cardiopulmonary bypass, but there were no significant differences in the changes
      in cytochrome aa3 between any stage in any of the patient groups. Using this non
      invasive technique, cooling was shown to reduce cerebral FOE. During rewarming on
      bypass there was an increase in cerebral FOE only in patients who had had
      continuous flow bypass. In contrast, the cerebral FOE in those with circulatory
      arrest remained constant after arrest and during the duration of the study. This
      may have implications for the timing of hypoxic brain injury.

PMID- 9534674
TI  - New chart to evaluate weight faltering.
AB  - A new chart was designed to aid accurate identification of weight faltering and
      failure to thrive. It provides guidance on the lower limits of expected weight
      gain for children, whatever their initial centile position. The chart's
      theoretical basis, the process of its construction, and its evaluation are
      described in this paper. Evaluation was by a self completion questionnaire, where
      respondents answered questions about a range of standardised growth patterns,
      plotted on old and new charts. Forty five health visitors, 28 general
      practitioner principals and registrars, and nine community paediatricians
      provided 328 chart ratings. These showed that the new format significantly
      increased the proportion of correctly rated charts (old: 45 (28%); new: 82
      (51%)), with the greatest impact in severe cases. This suggests that the new
      chart improves the precision of judgments made about weight gain in infancy.

PMID- 9534673
TI  - Kawasaki disease in Australia, 1993-95.
AB  - AIM: To describe the epidemiology, management, and rate of cardiac sequelae of
      Kawasaki disease in Australia. DESIGN: Cases were notified to the Australian
      Paediatric Surveillance Unit, an active national surveillance scheme, from May
      1993 to June 1995. RESULTS: 139 cases of Kawasaki disease were confirmed. In
      1994, the annual incidence was 3.7/100,000 children < 5 years old. Sixteen
      children were not admitted to hospital. Coronary artery abnormalities were
      reported in 35 (25%) children. Two patients were diagnosed at postmortem
      examination. Sixty six per cent of patients were diagnosed within 10 days of
      onset and 81% of these received intravenous gammaglobulin within 10 days. Forty
      five of the notified children did not fulfil the study criteria because of
      streptococcal infection or insufficient clinical criteria. One child with
      streptococcal infection had coronary artery dilatation. CONCLUSION: Diagnosis of
      Kawasaki disease was delayed beyond 10 days in one third of patients, and almost
      20% of children who could have received gammaglobulin within 10 days did not. The
      distinction between Kawasaki disease, streptococcal infection, and other possible
      diagnoses is problematic in some children.

PMID- 9534675
TI  - Gastro-oesophageal reflux in infants under 6 months with cystic fibrosis.
AB  - AIM: To establish the incidence of pathological gastro-oesophageal reflux (GOR)
      in newly diagnosed infants with cystic fibrosis and to identify clinical
      predictors of increased reflux. METHODS: 26 infants with cystic fibrosis less
      than 6 months of age (14 male, 12 female; mean (SEM) age 2.1 (0.21) months, range
      0.8 to 5.6 months) underwent prolonged oesophageal pH monitoring (mean duration
      27.1 (0.49) hours; range 21.3 to 30.2 hours). Reflux symptoms, anthropometric
      variables, pancreatic status, meconium ileus, genotype, and chest x ray findings
      were correlated with pH monitoring data. RESULTS: Five infants (19.2%) had an
      abnormal fractional reflux time of greater than 10%, seven (26.9%) of 5-10%, and
      14 (53.8%) of below 5%. Infants who presented with frequent vomiting had a
      significantly higher fractional reflux time than infants who had infrequent or no
      vomiting. There was no significant association between abnormal chest x rays and
      pathological GOR. Sex, genotype, nutritional status, meconium ileus, and
      pancreatic enzyme supplementation were not significantly associated with
      pathological GOR. CONCLUSIONS: About one in five newly diagnosed infants with
      cystic fibrosis had pathological GOR. Pathologically increased reflux was present
      before radiological lung disease was established. Apart from frequent vomiting,
      no useful clinical predictors of pathological reflux were found.

PMID- 9534676
TI  - Nitric oxide metabolites in cystic fibrosis lung disease.
AB  - Although the activity of nitric oxide (NO) synthases are increased in lung tissue
      of patients with cystic fibrosis, the concentrations of nasal and exhaled NO have
      recently been found to be decreased in cystic fibrosis. This could either be due
      to reduced NO formation or metabolism of NO within airway fluids. In this study,
      the stable NO metabolites, nitrate and nitrite, were determined in the saliva and
      sputum of 18 stable cystic fibrosis patients, 21 cystic fibrosis patients during
      a pulmonary exacerbation, and in saliva and endotracheal secretions of normal
      controls. Median saliva concentrations of NO metabolites (nitrate plus nitrite)
      were 704 mumol/l (95% confidence interval (CI) 419 to 1477) in stable cystic
      fibrosis patients, 629 mumol/l (95% CI 382 to 1392) in cystic fibrosis patients
      presenting with pulmonary exacerbation, and 313 mumol/l (95% CI 312 to 454) in
      controls. Median sputum NO metabolite concentration in stable cystic fibrosis was
      346 mumol/l (95% CI 311 to 504). This was not significantly different from cystic
      fibrosis patients presenting with pulmonary exacerbation (median 184 mumol/l, 95%
      CI 249 to 572), but significantly higher than in endotracheal secretions of
      controls (median 144 mumol/l, 95% CI 96 to 260). Sputum NO metabolite
      concentration in cystic fibrosis pulmonary exacerbation significantly increased
      during antibiotic treatment. A positive correlation was observed between sputum
      NO metabolites and lung function in stable cystic fibrosis, suggesting less
      airway NO formation in cystic fibrosis patients with more severe lung disease.
      These data indicate that decreased exhaled NO concentrations in cystic fibrosis
      patients may be due to retention and metabolism of NO within the airway
      secretions. However, sputum NO metabolites are not a useful marker of airway
      inflammation in cystic fibrosis lung disease.

PMID- 9534677
TI  - Hyporesponsiveness to intradermal administration of hepatitis B vaccine in
      insulin dependent diabetes mellitus.
AB  - The immune response to intradermal or intramuscular hepatitis B vaccine in 18
      children with insulin dependent diabetes mellitus (IDDM) compared with 24 healthy
      children was studied. Patients were divided into responders, hyporesponders, and
      non-responders according to their antihepatitis B serum concentrations after
      hepatitis B vaccination. We also studied HLA class II antigen distribution and
      did delayed type hypersensitivity (DTH) tests on children with IDDM and controls.
      No difference in the immune response (antihepatitis B surface antigen antibody
      titres) was found with intramuscular administration, whereas with intradermal
      administration a statistically lower immune response (p < 0.001) was observed in
      children with IDDM v controls. This hyporesponsiveness cannot be attributed to
      HLA class II antigen distribution because their frequency was the same in both
      groups of children with IDDM. It is suggested that the poor immune response to
      intradermal hepatitis B vaccine may be due to impaired macrophage activity
      resulting in failure of antigen presentation, which may be of importance in the
      immune dysfunction in children with IDDM. This hypothesis is suggested by a
      significantly lower score on a DTH test to a battery of antigens in the IDDM
      group when compared with controls. It is therefore suggested that when the
      hepatitis B vaccination is offered to children with IDDM it may be preferable to
      give it intramuscularly.

PMID- 9534678
TI  - Preliminary clinical evaluation of meningococcal disease and bacterial meningitis
      by ultrasonic enhancement.
AB  - Antigen detection in the urine and serum may be useful in the diagnosis of
      suspected meningococcal disease, especially after previous antibiotic treatment.
      Current test card procedures using commercial agglutination kits are often too
      insensitive to contribute to diagnosis. Diagnosis of meningococcal disease rose
      from 37% with the test card procedure to 74% following ultrasonic enhancement.

PMID- 9534679
TI  - Persistence of protective immunity after postexposure prophylaxis of varicella
      with oral aciclovir in the family setting.
AB  - The persistence of protective immunity after postexposure prophylaxis against
      varicella using oral aciclovir was evaluated in the family setting. Sixty one of
      78 recipients of oral aciclovir were assessed by questionnaire, and 13 of 61 were
      evaluated for serum antibody to varicella zoster virus (VZV) using the
      fluorescent antibody to membrane antigen method. The observation period ranged
      from 33 to 50 months. None of those (n = 44) who had initially seroconverted to
      VZV after aciclovir prophylaxis developed breakthrough varicella. All 13 who had
      serology repeated still had titres > or = 4. Antibody titres in those who had
      histories of re-exposure to the virus were significantly higher than in those who
      had not (p < 0.01).

PMID- 9534680
TI  - Cat scratch disease in Greece.
AB  - An indirect fluorescent antibody test for Bartonella henselae, B quintana, and B
      elizabethae was performed in all 18 children who presented to our paediatric
      outpatient clinic with cat scratch disease over a six year period. Serum samples
      were taken on admission, after 15 days, and after six months. Diagnosis was
      confirmed in 15 patients (83%) and was based on seroconversion or a fourfold
      change of the antibody titre to B henselae in 12 patients and on a single high
      titre (> 128) in three patients. Lymphadenopathy was present in all patients,
      erythema nodosum in one, osteomyelitis in one, hepatitis in one, transverse
      myelitis in one, and liver or spleen granulomata, or both, in three patients. Cat
      scratch disease developed in autumn or winter in 12 patients. All had a history
      of physical contact with a cat. Our study shows that our clinical suspicion was
      accurate in the diagnosis of cat scratch disease in a high percentage of patients
      presenting to a hospital and that indirect fluorescent antibody testing for B
      henselae is a useful diagnostic tool.

PMID- 9534682
TI  - Serum bicarbonate and dehydration severity in gastroenteritis.
AB  - The concentration of bicarbonate was measured in serum samples from 106 children
      with gastroenteritis and dehydration. A concentration less than 22 mmol/l was
      more common in children with severe dehydration, but the magnitude of bicarbonate
      reduction was not significantly different with increasing degrees of dehydration.
      Doctors should not rely on the serum bicarbonate concentration when assessing
      fluid deficit.

PMID- 9534681
TI  - Analysis of mycoplasmal pleural effusion by the polymerase chain reaction.
AB  - Ten pediatric patients with mycoplasmal pleuritis were tested for the presence of
      Mycoplasma pneumoniae in pleural fluid by the polymerase chain reaction (PCR).
      Three of the four PCR positive cases left a persistent consolidation. The
      remaining one was an infant who required mechanical ventilation. PCR may be
      useful in predicting delayed resolution of roentgenographic abnormality.

PMID- 9534683
TI  - War and children.

PMID- 9534684
TI  - Do seizures damage the brain? The epidemiological evidence.

PMID- 9534685
TI  - Staphylococcal scalded skin syndrome.

PMID- 9534686
TI  - Diagnosis and management of benign intracranial hypertension.

PMID- 9534687
TI  - Susceptibilities to aciclovir in viral isolates from children with varicella.

PMID- 9534688
TI  - Randomized trial of suprapubic puncture versus urethral catheterisation for
      cystography.

PMID- 9534689
TI  - Preclinical diagnosis of abdominal tumours by ultrasound examination.

PMID- 9534690
TI  - Minor head injury.

PMID- 9534691
TI  - CT scanner dosimetry.

PMID- 9534692
TI  - Radiotherapy in patients with cardiac pacemakers.
AB  - Patients with permanent cardiac pacemakers occasionally require radiotherapy.
      Therapeutic irradiation may cause pacemakers to malfunction due to the effects of
      ionizing radiation or electromagnetic interference. Modern pacemakers, using
      complementary metal oxide semiconductor (CMOS) circuitry, differ from older
      bipolar semiconductor devices both in their sensitivity to damage and the types
      of malfunction observed. The mechanisms and types of radiotherapy-induced
      pacemaker malfunction are described and in vitro and in vivo studies of pacemaker
      irradiation are reviewed. Some simple precautions are recommended during the
      planning and administration of radiotherapy to minimize the risk of harm to
      patients with pacemakers.

PMID- 9534693
TI  - A comparison of T2 and gadolinium enhanced MRI with CT myelography in cervical
      radiculopathy.
AB  - Two MRI strategies which have been reported to be effective in assessing cervical
      exit foramina, were prospectively compared with CT myelography in 20 patients
      with cervical radiculopathy. The first strategy utilized 3D T2* images, the
      second gadolinium enhanced 2D T1 images. Gadolinium (dimeglumine gadopentetate,
      Schering Ltd) enhanced images did not confer any benefit in the investigation of
      this condition, probably due to enhancement of herniated disc material and
      osteophytes adjacent to the neurocentral joint. Three-dimensional (3D) T2* white
      cerebrospinal fluid images had an accuracy approaching 90% for the diagnosis of
      foraminal encroachment, compared with a gold standard. MRI including a 3D T2*
      sequence is thus an acceptable primary investigation for cervical radiculopathy,
      but when the findings are incompatible with clinical symptomatology, CT
      myelography is still indicated.

PMID- 9534694
TI  - Dual phase spiral CT in the detection of small insulinomas of the pancreas.
AB  - Dual phase contrast enhanced spiral computed tomography (DPSCT) has the potential
      to improve detection of small insulin secreting islet cell tumours of the
      pancreas. Seven patients with biochemically proven insulinoma, who had previously
      undergone a range of negative radiological procedures, were referred for DPSCT.
      Images of the pancreas were obtained using 3 mm collimation in the arterial and
      arteriovenous perfusion phase following the rapid injection of contrast medium.
      Six tumours were localized in seven patients. The six insulinomas identified on
      DPSCT ranged in size from 6 mm to 18 mm and were located in the uncinate process
      (2), head (1), neck (2) and body (1). All six tumours were detected in the
      arterial phase and four in the arteriovenous phase. The four insulinomas detected
      on both perfusion phases were more conspicuous in the arterial phase in three
      patients and more conspicuous in the arteriovenous phase in one patient. In
      conclusion, high resolution arterial phase acquisition of the pancreas is very
      valuable in the detection of small insulinomas.

PMID- 9534695
TI  - Effect of radiographic contrast media on histamine release from human mast cells
      and basophils.
AB  - Radiographic contrast media (RCM) cause histamine-dependent allergic-like
      reactions. The direct effects of diatrizoate (high osmolar ionic monomer),
      ioxaglate (low osmolar ionic dimer), iopromide (low osmolar non ionic monomer)
      and iotrolan (iso-osmolar non ionic dimer) at the concentration of 200 mgI ml-1
      (60 min exposure) on the release of histamine from human basophils, human lung
      mast cells (HLMC), and human skin mast cells (HSMC) were investigated.
      Diatrizoate induced 48 +/- 4% histamine release in basophils, 15 +/- 3% in HLMC
      and 25 +/- 6% in HSMC. The remaining RCM were relatively ineffective activators
      of histamine release in both HLMC and HSMC (ioxaglate 4 +/- 1% and 4 +/- 1%,
      iopromide 5 +/- 1% and 7 +/- 2%, iotrolan 7 +/- 2% and 10 +/- 3%, respectively).
      Both iotrolan and ioxaglate were effective in basophils inducing 21 +/- 3% and 24
      +/- 6% histamine release, respectively, whereas iopromide was relatively
      ineffective (7 +/- 4%). Diatrizoate induced histamine release from all three cell
      types with optimal levels of histamine release after a 2-4 h incubation although
      significant levels occurred within 15 min. Dose-dependent histamine release from
      HLMC occurred in all four types of RCM, the largest response (37 +/- 3%) being
      produced by diatrizoate. The effect of osmolality on histamine release was
      investigated using different concentrations of mannitol solutions (0.25, 0.5 and
      1 M). Histamine release from HLMC, HSMC and basophils after 90 min exposure to
      mannitol (1 M) was 24 +/- 2% (p < 0.05), 9 +/- 3% (p = 0.06) and 49 +/- 1% (p <
      0.05), respectively, suggesting that hyperosmolality per se can induce histamine
      release from basophils and mast cells. Diatrizoate-induced histamine release in
      all three cell types was significantly reduced by lowering the temperature to 0
      degree C and partially attenuated by the metabolic inhibitors antimycin A (1
      microM) and 2-deoxyglucose (5 mM), and by the omission of glucose from the buffer
      solution. Diatrizoate-induced histamine release was not dependent on
      extracellular calcium. These data suggest that diatrizoate induces histamine
      release at least in part by non-cytotoxic mechanisms.

PMID- 9534696
TI  - The magic angle phenomenon in tendons: effect of varying the MR echo time.
AB  - Increased signal intensity on magnetic resonance (MR) imaging of tendons arising
      from the magic angle phenomenon is well recognized. This study aimed to evaluate
      the effect of varying the echo time (TE) upon tendon signal intensity, and to
      determine if a modified TE value produces acceptable T1 and proton density (PD)
      weighted images. Fresh bovine tendons were imaged in a 1.5 T MR scanner using
      spin echo (SE) T1 and PD weighted sequences and utilizing a number of different
      coils. For each set of sequences, the tendon was orientated at 55 degrees to the
      main magnetic field (B0) and imaged using constant TR and incremental TE values.
      Signal intensity was measured on images at each TR/TE value and compared with the
      signal intensities of tendons orientated at 0 degree to B0, obtained using
      minimum TE values. This experiment was repeated with a 1.0 T MR scanner and
      utilizing a spine coil. The Achilles tendon of a human volunteer was similarly
      imaged using a general purpose flex coil. For bovine and human tendons orientated
      at 55 degrees to B0, the signal intensities decreased exponentially with
      increasing TE. A critical TE value exceeding 37 ms, for each sequence, reduced
      the signal intensities to the levels obtained with the tendons orientated at 0
      degree to B0, such that the magic angle phenomenon could be avoided. Although
      there was variability of the signal intensities with different coils, the
      critical TE value remained constant and the anatomical clarity was not degraded.
      The critical TE value was unaltered using two MR scanners of different field
      strengths.

PMID- 9534697
TI  - Hydatid cysts of the liver: two cautionary signs.
AB  - The purpose of this paper is to evaluate the significance of two CT findings:
      evidence of an exophytic component of part of a hydatid cyst and dilated ducts in
      the vicinity of a cyst. The CT scans and clinical records of 63 patients were
      reviewed. There was evidence that cysts with an exophytic component are probably
      unstable and unsuitable for treatment by percutaneous drainage or prolonged
      medical treatment. Dilated pericystic ducts are a relative contraindication to
      nonsurgical treatment because of the danger of complicating biliary obstruction.
      Surgery should not be delayed unduly when either sign is encountered.

PMID- 9534698
TI  - Estimation of effective dose in some digital angiographic and interventional
      procedures.
AB  - In general, effective dose values for similar interventional vascular radiology
      (IVR) procedures are different. This is due to problems with the classification
      of radiological procedures, which make comparisons difficult. Patient size,
      examination technique and clinical condition as well as the skill of the medical
      radiologists also affect effective dose. Currently, there is a broad agreement on
      the classification of similar procedures so that effective dose estimates can be
      made from measurements of the dose area product (DAP). Thus, reference dose
      values may be established and comparative studies between different services and
      hospitals can be made. The objective of this study is to provide dose data for
      some digital angiographic and interventional procedures. Values of measured DAP
      for 143 patients for five types of procedures are presented. Procedures
      investigated were abdominal angiography, arteriography of lower limbs, biliary
      drainage, embolization of spermatic vein and nephrostomy. All the procedures were
      performed using digital equipment. Values of DAP and effective dose were 30 Gy
      cm2 and 6.2 mSv for arteriography of lower limbs and 150 Gy cm2 and 38.2 mSv for
      biliary drainage. In each one of these procedures, effective dose values per
      minute of fluoroscopy and per radiography film have been calculated. It is
      possible to use this information for the rapid estimation of effective dose.

PMID- 9534700
TI  - A simple method for investigating the effects of non-uniformity of radiofrequency
      transmission and radiofrequency reception in MRI.
AB  - Inhomogeneity of the transmitted or received B1 field leads to intensity
      variations in MR images and spatial dependence in apparent concentration in MR
      spectra. We describe a simple method for investigating such variations. The
      transmitted B1 field can be measured both in vivo and in vitro which allows
      investigation of sample dependent effects that can not be measured on phantoms.
      For homogeneous regions the method also allows the received B1 field to be
      measured both in vivo and in vitro. Our method uses only a standard spin echo
      pulse sequence and simple region of interest analysis and should be implementable
      on any commercial scanner. The method is demonstrated using a variety of
      transmission and reception radiofrequency coils both in vivo and in vitro.

PMID- 9534699
TI  - Objective assessment of phantom image quality in mammography: a feasibility
      study.
AB  - The need for test objects in mammography quality control programmes to provide an
      objective measure of image quality pertinent to clinical problems is well
      documented. However, interobserver variations may be greater than the
      fluctuations in image quality that the quality control programme is seeking to
      detect. We have developed a computer algorithm to score a number of features in
      the Leeds TOR(MAX) mammography phantom. Threshold scoring techniques have been
      applied in the first instance; scoring schemes which utilize measures such as
      signal-to-noise ratio and modulation have also been formulated. This fully
      automatic algorithm has been applied to a set of 10 films which have been
      digitized at 25 microns resolution using a Joyce-Loebl scanning
      microdensitometer. The films were chosen retrospectively from quality control
      test films to demonstrate: (a) a range of optimized imaging systems, and (b)
      variation from the optimum. The performance of the algorithm has been compared
      with that of five experienced observers, and has been shown to be as consistent
      as individual observers, but more consistent than a pool of observers. Problems
      have been encountered with the detection of small details, indicating that a more
      sophisticated localization technique is desirable. The computer performs more
      successfully with the scoring scheme which utilizes the full imaging information
      available, rather than with the threshold-determined one. However, both the
      observers and the computer algorithm failed to identify the non-optimum films,
      suggesting that the sensitivity of the TOR(MAX) test object may not be adequate
      for modern mammography imaging systems.

PMID- 9534701
TI  - Broad beam attenuation of kilovoltage photon beams: effect of ion chambers.
AB  - In kilovoltage X-ray treatment, beam shaping and shielding normal tissue are
      accomplished by thin sheets of lead cutout, the thickness of which is selected
      based upon either published data or measurements. Available broad beam
      attenuation (BBA) data are found to be unsatisfactory and are the subject of this
      investigation. BBA is defined as the ratio of intensity with (I) and without (I0)
      attenuating medium for a large field in a phantom. BBA = I(x,t,E)/I0(x,0,E),
      where x is the depth of measurement, t is the thickness of attenuator, and E is
      the beam energy. The depth x should be zero for kilovoltage beams and dmax for
      megavoltage beams. Unfortunately, x is limited by the window thickness which is
      the core of this study. A Farmer-type cylindrical ion chamber and three parallel
      plate ion chambers (Capintec, PS-033; Markus; and Holt) were used to measure BBA
      for kilovoltage beams from a Siemens Stabilipan unit. Results indicate that
      attenuation is strongly dependent on the window thickness. For the 240 kVp beam,
      the thickness of lead for 5% and 1% transmissions are 3.1 mm, and 5.2 mm,
      respectively, with the Capintec chamber. The corresponding values of lead
      thickness for the Markus chamber are 2.3 mm and 4.0 mm; for the Holt chamber the
      values are 1.1 mm and 2.2 mm; and for the cylindrical chambers the values are 1.1
      mm and 2.3 mm, respectively. Similar variabilities in lead thickness with ion
      chambers were also noted for the other kilovoltage beams. The large differences
      in lead thicknesses produce enormous clinical errors, especially for shielding
      eye and other critical structures. For small thickness of lead (< 0.1 mm), a 20
      fold increase in surface dose could be observed instead of usual beam
      attenuation. This is due to intense low energy photoelectrons liberated from lead
      sheets in the contact with tissue. It is concluded that the lead thickness
      required to shield normal tissue varies with ion chamber. Until national or
      international guidelines for broad beam transmission measurements are
      established, the shielding materials in contact with skin should be coated with a
      thin (> or = 0.3 mm) low atomic number medium. In such a situation, transmission
      measurements will be independent of the choice of an ion chamber.

PMID- 9534702
TI  - Modified radial head--capitellum projection in elbow trauma.
AB  - A new technique is described for evaluating trauma to the elbow. The modified
      radial head--capitellum view is an alternative radiological projection to that
      described by Greenspan and Norman (the radial head--capitellum view). This new
      projection is useful in demonstrating minimally displaced or non-displaced
      fractures of the radial head, capitellum and coronoid process.

PMID- 9534703
TI  - A flow model of cerebral aneurysms for use with power Doppler studies.
AB  - It has recently been observed using power Doppler that cerebral aneurysms appear
      to change size through the cardiac cycle. The purpose of this study was to
      develop a pulsatile flow model of cerebral aneurysm expansion and to investigate
      whether the observations of pulsation could be confirmed using the model. The
      model consisted of a latex bubble glued onto the side of a latex tube. A computer
      controlled pump was used to generate pulsatile flow. The degree of bubble
      expansion was adjusted by the use of flow restrictor placed in the downstream
      section of the flow rig. Ultrasound images were acquired using an Acuson 128
      XP/10V colour flow scanner. True expansion (maximum area/minimum area) was
      measured from the B-scan image using a 7 MHz probe. Three observers measured
      expansion of the simulated aneurysm from the power Doppler images using a 2 MHz
      probe. Expansion measured with the power Doppler decreased as the colour gain
      setting increased, and decreased as the persistence increased. The true expansion
      of 1.43 was comparable with the colour gain set optimally for a persistence value
      of 3. The model allows simple investigations of the relationship between true
      aneurysm expansion and that measured from the power Doppler images. Colour gain
      and persistence settings must be standardized in clinical studies.

PMID- 9534704
TI  - Thymic sarcoma in childhood.
AB  - Sarcoma of the thymus is exceedingly rare, especially in children. We report a
      case of thymic sarcoma in a child, including the imaging findings which have not
      been previously described.

PMID- 9534705
TI  - Total skin electron beam irradiation in scleromyxoedema.
AB  - We report a 44-year-old male with generalized progressive scleromyxoedema treated
      by total skin electron beam therapy (TSEBT) which produced a marked improvement
      in the skin lesion. TSEBT can provide effective treatment for patients with
      widespread skin involvement in scleromyxoedema.

PMID- 9534706
TI  - Recurrent follicular carcinoma-oxyphilic cell type (Hurthle cell carcinoma) of
      the thyroid, imaging with iodine-131 and technetium-99m tetrofosmin before and
      after radiotherapy.
AB  - A 68-year-old male with recurrence of malignant follicular carcinoma-oxyphilic
      cell type of the thyroid after surgery underwent whole body scintigraphy with
      131I-sodium iodide and 99Tcm-tetrofosmin (Myoview). 131I scanning demonstrated
      local uptake most likely to be in the normal remnant, but 99Tcm-Myoview images
      delineated recurrence of the carcinoma in the neck, with more extensive
      involvement. We believe that a combination of 131I and 99Tcm-tetrofosmin imaging
      may be useful to assess the extent of disease in patients with recurrent Hurthle
      cell type carcinoma of the thyroid.

PMID- 9534707
TI  - CT and MRI appearances of sarcomatous change in chronic pelvic endometriosis.
AB  - Endometriosis is a relatively common condition in pre-menopausal women. Rarely,
      endometrial malignancy may arise in and co-exist with endometriosis. In this case
      report, the findings on CT and MRI which indicated this development are
      described. Multiple image-guided biopsies showed features consistent with
      endometriosis and the diagnosis was not confirmed histopathologically until
      formal laparotomy and open biopsy.

PMID- 9534708
TI  - Diseases that simulate acute appendicitis on ultrasound.
AB  - Ultrasound is useful in the assessment of patients with possible appendicitis. A
      diagnosis of appendicitis can be made in patients with persistent right lower
      quadrant pain when a non-compressible appendix greater than 6 mm in diameter is
      shown. When a normal appendix is affected by an adjacent lesion, reactive
      inflammation can cause secondary enlargement of the appendix. This article
      reviews ultrasound findings in conditions which can clinically mimic acute
      appendicitis. Examples of Crohn's disease, tuboovarian abscess, typhilitis,
      sigmoid diverticulitis, perforated sigmoid neoplasm, perforated peptic ulcer,
      perforated acute cholecystitis, caecal carcinoma and appendiceal tumours are
      included.

PMID- 9534710
TI  - EC Directive: 97/43/Euratom.

PMID- 9534709
TI  - Case of the month. Double and nothing.

PMID- 9534711
TI  - Technetium-99m sestamibi scintigraphy, MRI and venous blood sampling in
      persistent and recurrent hyperparathyroidism.

PMID- 9534712
TI  - X-ray tubes--continuous innovative technology.
AB  - The X-ray tube is one of the most important components in any X-ray system. In
      the beginning, physicists and physicians used gas ion tubes. The so-called
      Coolidge tube applied a high vacuum and is still used today. Medical examinations
      have required continuously improved designs of X-ray tubes (smaller focal spots
      at a higher output). The principle of the Goetze line focus is still applied in
      any diagnostic X-ray tube. Different anode materials and the rotating anode
      contributed to an increased output and reduced exposure time. Bearings needed
      special attention. Spiral groove bearings are the most advanced design today. The
      heat storage capacity of the anode and the tube housing assembly influences
      examination time and patient throughput. Cardiac imaging required less motion
      blurring in cine film images and increasing radiation exposure in interventional
      procedures called for measures to reduce dose. Protection against radiation and
      electric shock has always been a concern of design engineers. Focal spot sizes
      dedicated to specific applications and heat management within the total tube
      housing assembly will be future issues. Even with the event of ultrasound and MR
      technology, X-ray procedures will still be applied for diagnostic and
      interventional purposes.

PMID- 9534713
TI  - Radiation protection--lessons from the past.
AB  - This is a historical review of selected events in radiation protection of medical
      relevance since the discovery of X-rays. The report concentrates on the period
      1895-1970. Key points were difficulty of measuring dose, rapid dissemination of
      the use of radiation for all sorts of illness, and regulation by professional
      bodies rather than by legislation. Both World Wars saw a huge expansion in the
      use of ionizing radiation, but the second war prevented international
      collaboration, which had begun formally in 1925. Early radiation deaths, and
      nuclear accidents have caused concerns about radiation safety, and although dose
      limits have been successively reduced, these concerns have not been overcome.
      Since the Second World War radiation safety has been subject to more and more
      legislation although professional bodies still have an important advisory role.
      Development of the main radiation safety committees both in the UK, US and
      internationally is described with emphasis on the particular role of the British
      Institute of Radiology.

PMID- 9534714
TI  - Fractionation in radiotherapy: a view from the clinic.
AB  - A century of the evolution of the fractionation of radiotherapy has brought
      clinical oncologists to the testing of protocols in randomized controlled
      clinical trials. The British Institute of Radiology's pioneering trials, together
      with more recent studies, are described and future developments suggested.

PMID- 9534715
TI  - Target volume definition in radiation therapy.
AB  - Target volume definition in radiation therapy is a broad field of
      interdisciplinary research. We give a brief history of clinical research in this
      field and outline some remarkable steps which led to the well-defined target
      volume concepts. The challenges in target volume definition for high-precision
      conformal radiation therapy are discussed, and possibilities of improving target
      volume definition, such as the integration of modern imaging modalities and the
      use of computer-based systems to support the radiation oncologist are indicated,
      as well as novel techniques for increasing the accuracy of patient positioning.
      All these tools should be evaluated with regard to their potential for increasing
      the therapeutic ratio and, as appropriate, should be implemented in clinical
      practice. However, target volume definition is a complex process influenced by
      many factors, currently under investigation. While questions remain in this
      field, and the impact of the influencing factors is not defined, the process of
      target volume definition should remain the subject of clinical research.

PMID- 9534716
TI  - The volume effect in radiotherapy--its biological significance.
AB  - Volume-related effects are an important consideration in clinical radiotherapy.
      The early rationale for the need to consider treatment volume has become clouded
      by the lack of clarity and a misinterpretation of some early clinical findings.
      In particular, there is a need to separate our understanding of biologically iso
      effective radiation responses from the clinical concept of normal tissue
      tolerance, as they relate to changes in treatment volume. Animal data, including
      those for large animals, are reviewed. These animal studies indicate the need for
      caution in extrapolating retrospective clinical data to new treatment situations,
      since the conclusions reached may have been dictated by dogma and not by careful
      consideration of different factors that may have been involved. These include
      anatomical and physiological factors, and variations in the dose distribution
      pattern to a specific organ or tissue. These biological factors could limit the
      general applicability of simple approaches based on mathematical models to the
      volume effect relationship in radiotherapy.

PMID- 9534717
TI  - Assessment of response following treatment for malignant disease.
AB  - Monitoring tumour response to therapy is an increasingly important aspect of
      oncological radiology. Cancer is increasing in incidence in the UK and recent
      advances in treatment have resulted in many more patients surviving with treated
      disease. Concurrent advances in imaging techniques over the past two decades
      permit us to obtain detailed morphological and functional information from
      treated tumours. This article reviews clinical strategies for imaging patients
      following treatment for cancer with particular reference to techniques which are
      currently under continuing scientific evaluation.

PMID- 9534718
TI  - Investigation and management of patients at high risk of developing cancer.
AB  - Recent developments in cancer genetics have revealed genes that render
      individuals susceptible to cancer. These families have a unique set of new
      problems and benefits that must be thought through for the potential good to be
      accrued from these discoveries. Individual patients seek early diagnosis and
      prevention strategies that challenge the limits of current knowledge. Some
      available methods have not yet been evaluated. There is a need for the evidence
      to support plans of care, and consistency is required from one centre to the next
      in the advice given. These familial cancers are often different from the more
      common sporadic cases, and so traditional treatments need to be tested again in
      the context of the new genetic knowledge. Three groups of cancers, breast, ovary
      and colon, have been used to illustrate the issues surrounding these high risk
      families, their investigation and care. In applying new strategies to these
      patients, ethical issues arise that are new to the medical world, and must be
      considered by the lay public. It is up to the medical profession, patients and
      society to use this knowledge to give benefit to a vulnerable group, and not to
      give unaffordable hopes and unnecessary anxieties.

PMID- 9534719
TI  - Nuclear magnetic resonance spectroscopy of cancer.
AB  - Nuclear magnetic resonance spectroscopy (MRS) offers a non-invasive approach for
      studying tumour biochemistry and physiology. This review highlights NMR nuclei
      (31P, 1H, 19F, 13C, 2H) that have been observed in both pre-clinical and clinical
      spectroscopic studies of cancer.

PMID- 9534720
TI  - MRI developments in perspective.
AB  - Following Paul Lauterbur's seminal 1973 paper in Nature, considerable work was
      needed to overcome a number of physical, engineering and technical problems
      before the new technique of magnetic resonance imaging (MRI) could be applied
      clinically. Much of that pioneering work was done in the UK. Since the first head
      and whole-body images were obtained in the late 1970s, MRI has become a widely
      used clinical imaging modality capable of yielding tomographic images of
      excellent spatial resolution and tissue contrast. This review outlines the
      historical development of MRI in the context both of the technical problems which
      had to be overcome, and of the clinical uses of MRI. Current areas of research,
      such as the use of MRI to map brain function, the measurement of physiological
      parameters such as tissue perfusion, and the use of open-access real-time MRI to
      guide interventional procedures, are briefly discussed.

PMID- 9534721
TI  - Interventional magnetic resonance imaging.
AB  - The development of minimally invasive surgical and interventional techniques has
      created a need for more accurate and sensitive image guidance and monitoring.
      Magnetic resonance imaging, with its superior soft tissue discrimination and
      multiplanar facilities, seems the obvious choice for an ideal image-guidance
      tool. Until recently, the employment of MRI in this role has been prevented by
      the physical constraints of conventional, closed-configuration machines. The
      problem has now been overcome by the development of an open design allowing both
      horizontal and vertical access to the patient in the scanner so that procedures
      can be performed concurrent with image acquisition. This configuration, together
      with the use of fast gradient echo sequences which can scan at speeds close to
      real time, means that a wide range of interventional procedures can be performed
      with on-line image guidance and monitoring. In addition, the versatility of the
      open design means that patients can assume physiological positions to allow
      dynamic joint imaging to be performed. This opens up a whole new field in the
      understanding of joint pathophysiology. This review article discusses these
      recent technological developments and their clinical applications. In particular,
      the potential role in guidance of biopsies, monitoring of thermal ablation
      techniques and applications in endoscopic surgery is outlined.

PMID- 9534722
TI  - The interventional magnetic resonance unit--the minimal access operating theatre
      of the future?
AB  - Interventional magnetic resonance units give the surgeon the potential to use
      intraoperative imaging to guide the surgical procedure. The advantages of
      magnetic resonance (MR) over other intraoperative imaging modalities include
      excellent soft tissue resolution, lack of ionizing radiation and the ability to
      reconstruct images in any desired plane. Postulated advantages include the
      ability to confirm adequate tumour resection, reduction in procedure magnitude
      and complication rate, shortened inpatient stay and the development of novel
      minimally invasive techniques including the use of thermal energy to destroy
      lesions. Fully MR compatible anaesthetic and patient monitoring equipment is
      available. However, before the MR-guided minimally invasive surgery can become a
      reality, much work is required in the assessment and development of MR compatible
      surgical instrumentation and equipment. This review describes the testing and
      development of instruments and equipment for MR image-guided surgery that we have
      undertaken. We describe the techniques we employ for open and minimal access
      surgery within this unique environment. The difficulties of operating within such
      an environment and the safety issues that this engenders are discussed. The
      current applications of intraoperative MR in the main surgical specialities are
      reviewed, and possible future areas of development for MR-guided minimally
      invasive surgery described.

PMID- 9534723
TI  - The appropriate use of computed tomography.
AB  - Computed tomography remains an exciting branch of radiology twenty years after
      its introduction into clinical medicine. The advent of spiral techniques has led
      to several recent developments. The current indications for its use are
      considered in the light of advances in ultrasound and magnetic resonance.

PMID- 9534724
TI  - CT virtual simulation.
AB  - Advances in computer technology and software design have enabled the concept of
      virtual simulation, first suggested by George Sherouse, to be realized. This
      article reviews the hardware and software requirements that provide a system that
      feels like a simulator and can facilitate the 3D planning process. Fast digital
      reconstruction of a radiograph from a CT data set provides true verification of
      treatment field design within the constraints of the virtual method. The clinical
      application of this technique is discussed in detail in relation to particular
      treatment sites.

PMID- 9534725
TI  - New and future developments in ultrasonic imaging.
AB  - In the first part of the review, recent developments in medical imaging
      technology are described. Developments in transducer materials and matching,
      leading to improvements in band-width and sensitivity are discussed. Improvements
      in dynamic range due to increased transducer sensitivity, lower electronic noise
      levels and more efficient filtering are then considered. The benefits of the
      application of digital signal processing (DSP) techniques to radiofrequency (RF)
      echo signals are described, including more precise filtering and beam forming,
      synthetic aperture and parallel receive beam forming. Finally, the current
      situation in regard to 1.5 D arrays, 3 D scanning, ultrasound computed tomography
      (UCT), harmonic imaging with contrast agents and elastography are discussed. In
      the second part, some predictions for future developments are made. These will be
      possible largely due to the power of DSP. Parallel transmissions will make more
      efficient use of time, allowing greater spatial and temporal resolution, and
      greater accuracy in Doppler imaging. Adaptive transmission tailoring will be
      used, where the pulse characteristics to each part of the image field are
      independently optimized, as will adaptive receive processing in which echo
      sequences from each part of the image are independently and optimally processed.
      An important potential development will be automatic feature recognition, making
      possible accurate compound scanning with high spatial resolution, and
      quantitative information about the spatial distribution of acoustic speed.
      Compound scanning will provide more complete visualization of all structures and,
      particularly when incorporated into intravascular probes, should greatly aid the
      investigation of arterial plaque morphology. Feature recognition will also make
      it possible to have UCT systems (array based in future) which require less than
      360 degrees access. Harmonic imaging without contrast agents, based simply on the
      inherent non-linearity of sound propagation in tissue, will become common. 2 D
      phased array transducer will permit symmetric beam focusing and scanning
      throughout a solid cone, greatly facilitating the development of 3 D scanning
      applications. Large 2 D arrays would have the potential to produce a five-fold
      increase in spatial resolution of a limited volume of tissue, or to measure the
      variation of backscatter with angle, as an aid to tissue characterization.
      Finally, ultrasound will be increasingly used to measure the elastic and dynamic
      properties of local regions of tissue.

PMID- 9534726
TI  - Radionuclide developments.
AB  - This review considers a number of recent important developments in nuclear
      medicine, and possible future introductions, priority being given to those
      products which are most likely to find a place in clinical practice. This
      includes both novel radiopharmaceuticals and progress with new types of imaging
      equipment. Three areas are chosen as being of particular importance: brain
      imaging, heart imaging, and diagnosis and therapy of cancer. In the brain, the
      clinical value of imaging regional cerebral blood flow and certain aspects of the
      neuroreceptor/neurotransmitter system are discussed. Cardiac imaging is
      considered in the light of recent work on diagnosis and risk assessment,
      investigating the hibernating myocardium, and the possible place of fatty acid
      imaging. Both diagnosis and therapy of cancer are increasingly important, and the
      use of radionuclides in these areas in considered.

PMID- 9534727
TI  - The future of digital imaging.
AB  - For most applications, conventional film based methods may be replaced by digital
      imaging. This trend is influenced technically by the advent of more efficient
      detectors, improved image processing methods, faster computers, brighter and
      sharper displays and larger systems for image storage and archiving. The
      evolution of digital imaging reflects the fast development of information
      technology. Work in radiology departments will change. Information systems will
      organize the registration and administration of patient data, the scheduling of
      examinations, management of work flow and the generation of reports. Images will
      be taken without film cassettes and will be directly displayed on monitors for
      reporting. Digital imaging provides greater flexibility in processing,
      transmitting and displaying images. A larger dynamic range and improved contrast
      resolution lead to a consistently high image quality. This must lead to new rules
      of diagnosing images and quality assurance. Interfaces are interrelating imaging
      modalities, displays, the administration and the archive system to each other.
      The resulting net has to be safe, stable and fault-tolerant. Digital imaging
      systems will depend much more on the proper function of the interrelated systems
      in the network.

PMID- 9534728
TI  - Thoracic imaging--then and now.
AB  - The chest radiograph has proved a robust diagnostic aid over the last century.
      The accumulation of knowledge about chest disease by radiography has been gained
      slowly during the last 90 years. New impetus has been given by the development of
      computed tomography and the recent refinements of high resolution and spiral
      computed tomography. The pathophysiological insights provided by these new
      techniques have been obtained in a remarkably short period, with the promise of
      more to come.

PMID- 9534729
TI  - Cardiac imaging: present status and future trends.
AB  - Cardiac imaging has developed rapidly in a number of different areas, to the
      extent that the clinical practice of cardiology is highly image dependent.
      Advances in cross-sectional and three-dimensional imaging using computed
      tomography and magnetic resonance imaging have now found a significant role in
      demonstrating cardiac anatomy and function alongside the more traditional role of
      ultrasound which with its intravascular use is becoming a part of intravascular
      cardiac therapy. The imaging of myocardial perfusion by nuclear medicine
      techniques including single photon emission tomography and positron emission
      tomography has grown to add substantial clinical and academic information on
      cardiac blood flow and metabolism.

PMID- 9534730
TI  - The future of arteriography and vascular interventional radiology.
AB  - Non-invasive vascular imaging techniques threaten to diminish the catheter skills
      which radiology trainees currently acquire during diagnostic angiography. This,
      coupled with the desire of some vascular surgeons to perform minimally invasive
      "endovascular surgery", may threaten the future of this radiological
      subspecialty, or perhaps it will help to create a new discipline incorporating
      surgical, medical and radiological skills.

PMID- 9534731
TI  - The future of barium radiology.
AB  - Barium radiology of the gastrointestinal tract has had a long history but its
      survival into the next century will be a challenge. The numbers of barium studies
      performed has declined in recent decades due to several factors; also, health
      care reforms in the United States will further impact on the use of barium
      examinations. The future status of these radiological procedures will change
      depending on these factors and the organ system being examined; an increased
      emphasis on functional evaluation of the gastrointestinal tract will also have an
      effect on the evolving role of barium radiology. We provide a brief historical
      review of the evolution of barium radiology in the twentieth century, discuss the
      present and changing status of the various gastrointestinal examinations, and
      offer our thoughts concerning the potential future of this specialty.

PMID- 9534733
TI  - The future for radiography practice.
AB  - In evaluating the future face of radiography practice, a historical review of
      developments to date has been undertaken, together with a look at the changes
      which will face the profession into the new millennium. This article focuses on
      changing healthcare provision, changing radiographic practice, the changing face
      of the healthcare professions and the changing focus of education and training.
      The opportunities for further development of the profession are explored along
      with an overview of some of the possible barriers to progress. Our contention is
      that radiographers are more than adequately prepared for a rapidly changing
      future. To ensure that they are prepared, however, it is essential for the
      profession to adopt an appropriate vision, formulate an achievable strategy, and
      promote a culture of professional practice which is able to respond adequately to
      the problems facing its continued existence.

PMID- 9534732
TI  - Bone densitometry: current status and future prospects.
AB  - Over the past decade, growing awareness of the impact of osteoporosis on the
      elderly population and the consequent costs of healthcare have stimulated
      development of new treatments to prevent fractures, together with new imaging
      technologies to assist in diagnosis. With its ability to perform high-precision
      measurements of bone mineral density (BMD) in the spine and hip, dual X-ray
      absorptiometry (DXA) is well suited to meet this latter need. However, there is
      continuing interest in smaller, less expensive, systems for assessing the
      peripheral skeleton. These include peripheral DXA scanning of the distal forearm
      and a variety of devices for performing quantitative ultrasound (QUS)
      measurements of broad-band ultrasonic attenuation (BUA) and speed of sound (SOS)
      in bone. Pivotal to all these developments is the demonstration in prospective
      studies that new technologies can reliably identify patients at risk of
      osteoporotic fractures. Whether DXA technology can meet the anticipated need for
      wider provision of diagnostic services is uncertain at present. The likely
      alternative is bone ultrasound. Although QUS technology is substantially cheaper
      than DXA and has proved its ability to predict fracture risk in the elderly, it
      is less precise, there is a lack of appropriate phantoms for quality control and
      there are doubts about how to interpret results in younger women.

PMID- 9534734
TI  - The Internet and radiology.
AB  - Basic Internet structures are introduced. Extrapolation from these basic
      structures may give clues to some future developments in radiology, including
      education and image interpretation. Cooperation between radiology professionals
      is no longer limited by geographical location and will allow the contributions
      from individuals to be judged by their creativity and content, regardless of
      their origin. The solution complex problems, such as information overload at the
      workstation, will need as many active minds as can be recruited.

PMID- 9534735
TI  - Electrical impedance tomography.
AB  - Electrical impedance tomography (EIT) is a technique which allows cross-sectional
      images related to the local electrical impedance within an object to be
      reconstructed from sets of measurements made on its surface. The main drive
      behind the development of EIT has been its possible application in medical
      imaging, as biological tissues are known to exhibit a wide range of electrical
      impedance and many physiological events are accompanied by electrical impedance
      changes. This article reviews the technical aspects of EIT as a medical imaging
      modality, and considers the range of applications over which it might be
      employed. Existing technical limitations and future developments are discussed.
      It is concluded that the future of EIT as a clinical diagnostic tool is likely to
      lie in the area of functional monitoring, where the capability of performing
      image-guided localized electrical impedance measurements with high acquisition
      speed, good sensitivity and no hazard can be exploited.

PMID- 9534736
TI  - Diagnostic imaging with light.
AB  - This paper reviews the evolution of optical imaging in diagnostic radiology and
      examines recent progress. Although the idea has been around for many decades,
      interest in the development of an effective method has never been so great.
      Optical imaging presents several potential advantages over existing radiological
      techniques. First, the radiation is non-ionizing and therefore reasonable doses
      can be repeatedly employed without harm to the patient. Second, optical methods
      offer the potential to differentiate between soft tissues with different optical
      absorption or scatter, but which are indistinguishable using other modalities.
      And third, specific absorption by natural chromophores (such as haemoglobin)
      allows functional information to be obtained. Principal clinical applications
      include a means of detecting breast disease and a cerebral imaging modality for
      mapping oxygenation and haemodynamics in the brain of newborn infants or cortical
      functional activity in adults. Past attempts to image tissues with light have
      been severely restricted by the overwhelming scatter which occurs when optical
      radiation spreads through tissue: however, recent innovations in technology have
      suggested once again that it may be a practical possibility.

PMID- 9534737
TI  - Surveillance of antibiotic susceptibility of Neisseria gonorrhoeae in the western
      Pacific.

PMID- 9534738
TI  - Bacterial vaginosis--more questions than answers.

PMID- 9534739
TI  - Reporting adverse drug reactions in HIV infection.

PMID- 9534740
TI  - STD vaccines--an overview.
AB  - OBJECTIVES: To describe the role and current status of vaccine research against
      sexually transmitted diseases (STDs). METHODS: The available literature was
      reviewed with particular emphasis on bacterial STDs. RESULTS: Strategic
      approaches to possible implementation of STD vaccine programmes were analysed.
      The status of vaccines against bacterial STDs (syphilis, chancroid, gonorrhoea,
      and chlamydia) is described in detail. CONCLUSIONS: The development of safe and
      effective STD vaccines offers a potent tool for the control of STDs, including
      direct and indirect prevention of HIV infection. Future priorities should be in
      the development of vaccines against gonorrhoea, chlamydia, and syphilis. When
      such vaccines become available, caution should be exercised to ensure that they
      do not interfere with the effectiveness of other prevention programmes.

PMID- 9534741
TI  - From human immunodeficiency virus (HIV) infection of the brain to dementia.
AB  - Human immunodeficiency virus (HIV) can cause both primary and secondary brain
      diseases. Numerous neuropathological studies have shown that up to 90% of
      patients with acquired immune deficiency syndrome (AIDS) have lesions in the
      nervous system. In this review, we discuss the entry of HIV into the brain, the
      general features of HIV associated neuropathology, the role of different brain
      cells in HIV mediated neuronal damage, and the putative molecular mechanisms
      involved. We conclude by correlating which factors might be important in the
      development of HIV associated dementia.

PMID- 9534743
TI  - Surveillance of antibiotic susceptibility of Neisseria gonorrhoeae in the WHO
      western Pacific region 1992-4. WHO Western Pacific Region Gonococcal
      Antimicrobial Surveillance Programme.
AB  - OBJECTIVE: To describe the establishment and outcomes of a regional programme of
      continuing long term surveillance of antibiotic susceptibility of Neisseria
      gonorrhoeae over the period 1992-4. METHODS: Laboratories in 17 countries in the
      WHO Western Pacific Region participated in a continuing programme of surveillance
      of the susceptibility of gonococci to an agreed group of antibiotics over 3
      years. Established techniques were used and these included quality control and
      proficiency testing systems. RESULTS: About 20,000 gonococci were examined over a
      3 year period. Resistance to the penicillins through beta lactamase production or
      chromosomal mechanisms was widespread, with further changes evident over the 3
      years. Spectinomycin resistance was infrequently encountered but high level
      tetracycline resistance was present in most participating centres, with some
      having high proportions of tetracycline resistant organisms. Quinolone resistance
      increased and became widespread throughout the region in the 3 years, ultimately
      involving all but one centre. Both the number and minimum inhibitory
      concentrations of quinolone resistant isolates increased markedly. CONCLUSIONS:
      Patterns of gonococcal resistance to antibiotics continue to evolve, at times
      rapidly, and have the potential for wide and rapid dissemination. Regional
      surveillance programmes can be developed by using and expanding existing
      resources. Data thus derived were applied to the development of appropriate
      treatment regimens in the region, and emphasised further the need for a global
      expansion of the programme of integrated surveillance of gonococcal resistance.

PMID- 9534742
TI  - Direct estimates of prevalent HIV infection in adults in England and Wales for
      1991 and 1993: an improved method.
AB  - OBJECTIVE: To estimate the number of prevalent HIV infections in England and
      Wales at the end of 1991 and 1993. METHOD: A direct method was used whereby
      population estimates derived from the National Survey of Sexual Attitudes and
      Lifestyle (NATSAL) and prevalence data from the Unlinked Anonymous HIV Prevalence
      Monitoring Programme (UAPMP) were combined to produce estimates of the number of
      adults infected and alive in the population. RESULTS: In the population of
      England and Wales the numbers of prevalent infections for defined transmission
      categories, at the end of 1993, were as follows: 12,600 through sex between men,
      2500 through injecting drug use, and 6900 through heterosexual intercourse. The
      overall estimate was 22,800 HIV seropositive individuals. CONCLUSIONS: The direct
      method attempts to provide an estimate of the number of HIV infections using
      population based survey data. These estimates are consistent with other
      approaches using independent methods. Such methods are essential for inferring
      recent HIV incidence, projecting future AIDS cases, and for healthcare planning.

PMID- 9534744
TI  - Genital Chlamydia trachomatis (serotypes D-K) infection in Jamaican commercial
      street sex workers.
AB  - OBJECTIVES: To determine the prevalence of genital Chlamydia trachomatis
      infections in commercial street sex workers (CSSW) in Jamaica. METHODS: The
      prevalence of C trachomatis infection was determined in 129 Jamaican CSSW using
      the direct fluorescent antibody (DFA) method and the isolation techniques which
      utilise fluorescent and iodine staining of endocervical cytobrush specimens
      cultured in McCoy cells. The seroprevalence of C trachomatis in the CSSW was also
      compared with that in blood donors (n = 435), using the microimmunofluorescence
      (MIF) test. RESULTS: The DFA detected C trachomatis in 16% (21/129) of the
      specimens. The prevalence as determined by the iodine and fluorescein stained
      cultures was 24% (31/129) and 25% (33/129) respectively. The overall prevalence
      of current chlamydial infection detected by the isolation techniques used was 25%
      (33/129). As determined by the MIF test, a statistically significantly higher
      seroprevalence rate of C trachomatis (95%, 61/64) was found in CSSW compared with
      blood donors (53%, 229/435; OR 22.6; chi 2 = 49.8; p < 0.001). The prevalence of
      current infection in CSSW as indicated by the isolation of C trachomatis was not
      influenced by history of previous pelvic inflammatory disease (PID), sexually
      transmitted disease, or condom use. N gonorrhoeae (9%) and Candida albicans (7%)
      were found in comparatively low frequencies, while Trichomonas vaginalis (0%) was
      not found in specimens from the CSSW. CONCLUSIONS: A high seroprevalence rate and
      a high rate of current infection with C trachomatis occur in Jamaican CSSW. In
      order to control the spread and prevent the severe clinical complications and
      sequelae of C trachomatis infection, the diagnosis and treatment in such high
      risk groups such as CSSW should be optimised.

PMID- 9534745
TI  - Epidemiology of genital warts in England and Wales: 1971 to 1994.
AB  - OBJECTIVE: To describe the epidemiology of genital warts in England and Wales
      over the period 1971 to 1994. METHOD: Retrospective study of available
      statistics. RESULTS: The rate of attendance for genital warts increased by 390%
      and 594% for men and women respectively between 1971 and 1994. Most of this
      increase occurred between 1980 and 1986. From 1986 to 1991 virtually no change
      occurred, but since 1992 the rate of attendance has risen by 15%. The ratio of
      male to female cases has declined steadily from 1.85 in 1971 to 1.34 in 1994.
      Rates of attendance for first attack in men were highest in the 20 to 24 year age
      group whereas for women it peaked in those aged 16 to 24 years. Regional data
      indicate that the rate of attendance has increased consistently over England and
      Wales during this period. CONCLUSIONS: Rates of genital warts have risen
      substantially over the past 25 years. If these are a reflection of changes in
      sexual behaviour then the rise since 1992 is of considerable concern particularly
      for the incidence of cervical cancer in the coming decades.

PMID- 9534746
TI  - Sexual relationships, risk behaviour, and condom use in the spread of sexually
      transmitted infections to heterosexual men.
AB  - OBJECTIVE: To examine the effect of patient defined non-regular sexual
      relationships and other risk behaviours on the incidence of sexually transmitted
      infections in heterosexual men and the role of condom use in the prevention of
      their spread. DESIGN: A prospective cross sectional study of sexual behaviour
      reported by a standardised self administered questionnaire in new patients who
      presented for screening and diagnosis. SETTING: A genitourinary medicine clinic
      in west London. SUBJECTS: 957 consecutive newly attending heterosexual men who
      completed a sexual behaviour questionnaire in 1993/94. MAIN OUTCOME MEASURES:
      Variables relating to sociodemographic status, sexual behaviour, condom use,
      sexually transmitted infections and testing for HIV infection, stratified by the
      reporting of non-regular partners. RESULTS: We found that the 65% of men who
      reported non-regular sexual partners were more likely to be white collar class (d
      = 7.5%, 95% CI = 1.3, 13.7) and to have had sexual intercourse with non-United
      Kingdom born women (d = 7.8%, 95% CI = 3.5, 12.2). They also reported coitarche
      before 16 years of age (d = 13.4%, 95% CI = 8.0, 18.8) and many more sexual
      partners both in the last year (d = 13.1%, 95% CI = 10.2, 16.0) and in their
      lifetime (d = 27.9%, 95% CI = 21.6, 34.2). They were significantly more likely to
      practise anal intercourse (d = 8.7%, 95% CI = 3.3, 14.1), to smoke (d = 16.3%,
      95% CI = 9.8, 22.6), to drink alcohol (d = 4.9%, 95% CI = 1.2, 8.6), and to have
      chlamydial infection (d = 5.7%, 95% CI = 2.2, 9.2), of which 30% was subclinical.
      Increasing condom use with regular partners correlated with decreasing incidence
      of urethral infection (gonorrhoeal and/or chlamydial infection) (p < 0.03) and
      candidal balanitis (p < 0.03) and a greater likelihood of no infection being
      detected (p = 0.0002). Use of condoms with non-regular partners was much more
      frequent than with regular partners (d = 21.4%, 95% CI = 16.7, 26.1). However, we
      found evidence of oral transmission of urethral gonorrhoea and chlamydial
      infection among men who reported always using condoms. HIV infection was found in
      only two men (0.2%), both of whom reported intercourse with non-United Kingdom
      born women. CONCLUSIONS: Heterosexual men who reported non-regular sexual
      relationships compensated for their increased risk lifestyle by using condoms
      more frequently and showed only an increased incidence of chlamydial infection.
      More consistent condom use with regular partners was significantly associated
      with the absence of sexually transmitted infection. These findings suggest that
      transmission between regular partners has been underestimated.

PMID- 9534748
TI  - Characterisation of Neisseria gonorrhoeae in semen during urethral infection in
      men.
AB  - OBJECTIVE: To determine the number of Neisseria gonorrhoeae organisms in urine
      and semen in men with gonococcal urethritis, and to compare selected phenotypic
      characteristics of organisms harvested from the urethra and semen. DESIGN:
      Samples from two groups of subjects were examined. Patients with symptomatic
      urethritis receiving treatment at an STD clinic, as well as six subjects with
      experimental urethritis. Semen and urine specimens were obtained after the
      urethral exudate was sampled. RESULTS: Using quantitative cultures, we found an
      average of 6 x 10(6) gonococci in urine or semen of 17 men with symptomatic
      urethritis seeking treatment at an STD clinic, and 2 x 10(4) gonococci in
      secretions of six male subjects with early experimental infection. Gonococcal
      outer membrane opacity (Opa) proteins and lipo-oligosaccharide (LOS) recovered
      from urine and semen of these subjects were very similar. CONCLUSIONS: Men with
      symptomatic gonorrhoea excrete a large number of gonococci in semen which is not
      affected by the duration of symptoms. The similar phenotype of organisms in urine
      and semen suggests the bacteria come from the same compartment. These data help
      to explain the efficiency of gonococcal transmission from men to their partners,
      and identify an appropriate target for a preventative vaccine or immunotherapy
      designed to reduce the inoculum in infected patients.

PMID- 9534747
TI  - An association between non-gonococcal urethritis and bacterial vaginosis and the
      implications for patients and their sexual partners.
AB  - OBJECTIVES: The aetiology of non-gonococcal urethritis (NGU) in a considerable
      proportion of men remains unaccounted for. We wished to investigate the possible
      aetiological role of bacterial vaginosis (BV), the commonest cause of abnormal
      discharge in women, in this condition. METHODS: We carried out two studies. In
      the first, case-control, study, we recruited men with and without NGU and
      examined their female partners for evidence of BV. The second, cohort design,
      study which ran concurrently with the first study involved recruiting women with
      and without BV and examining their male partners for evidence of NGU. The
      diagnoses of both NGU and BV were made microscopically to include symptomatic and
      asymptomatic individuals in both disease categories. RESULTS: In the case-control
      study 51 couples were recruited. Of these 39 men had NGU and 12 (31%) of their
      female contacts had BV. In contrast, of 12 men without NGU, only one (8%) of the
      female partners had BV (odds ratio 4.89, 95% CI: 0.51-42.27). When only Chlamydia
      trachomatis negative patients were considered, the odds ratio for an association
      between BV and NGU was increased to 6.77, 95% CI: 0.73-62.68). Thirty eight
      couples were recruited to the cohort design study. Of 17 women with BV, 12 (71%)
      of their male partners had NGU. In contrast, of 21 women without BV, seven (33%)
      of their male partners had NGU (p = 0.049, odds ratio 4.8). When only C
      trachomatis negative patients were considered, the significance of the
      association was increased (p = 0.037; odds ratio 5.42). CONCLUSIONS: An
      association exists between NGU and BV, and vice versa. If BV arises de novo the
      findings could help to explain the development of urethritis in stable sexual
      relationships.

PMID- 9534749
TI  - Effect of concurrent lower genital tract infections on cervical cancer screening.
AB  - BACKGROUND AND OBJECTIVES: Although women attending STD clinics are at high risk
      for cervical cancer, most STD programmes do not include Papanicolaou (Pap) smears
      in their routine screening procedures. Concerns regarding reliability of this
      test in a population with a high rate of active infection are often raised. The
      objective of this study was to analyse the associations between STD
      diagnosis/clinical syndromes and unsatisfactory and abnormal Pap smears. METHODS:
      Retrospective analysis of Pap results and medical records from women attending an
      inner city STD programme. RESULTS: Of the 1202 patients analysed, 3.2% had
      squamous intraepithelial lesions (SIL) and 3.5% had smears which were
      unsatisfactory because of the thickness of the specimen. There were no
      associations between STD diagnoses and SIL; however, the presence of cervical
      inflammation was significantly associated with SIL. Pap smears which were
      unsatisfactory because they were too thick were also associated with the clinical
      finding of cervical inflammation. CONCLUSIONS: The presence of active infection
      did not preclude the detection of SIL on Pap smears. The percentage of
      unsatisfactory smears resulting from inflammation was low.

PMID- 9534750
TI  - Type 1 cytokine response and treatment outcome of genital HPV lesions.
AB  - OBJECTIVES: To determine the role of type 1 cytokines as predictors of response
      to treatment of genital HPV lesions with laser ablation with or without adjuvant
      systemic interferon alpha 2b (IFN-alpha). METHODS: Measurement of serum
      interleukin 2 (IL-2), IL-2 soluble receptor alpha (sIL-2 alpha), interferon
      gamma, and human papilloma virus (HPV) DNA in patients undergoing treatment of
      genital HPV lesions with carbon dioxide laser and systemic IFN-alpha. A
      randomised, placebo controlled study of 92 cases with 6 months of follow up.
      RESULTS: High IL-2/sIL-2 alpha was associated with 60% to 70% protection against
      recurrences both in the IFN-alpha and placebo groups (OR = 0.4, 90%, CI 0.1-2.5;
      OR = 0.3, 90% CI 0.0-1.8, respectively). Diagnostic phase serum IL-2 predicted
      favourable outcome (OR = 0.2, 90% CI 0.0-1.0) in women with high load of HPV DNA
      or HPV 16/18 DNA regardless of the adjuvant therapy. CONCLUSIONS: Serum IL-2
      determinations may identify women with good prognosis following laser ablation of
      genital HPV lesions.

PMID- 9534751
TI  - Therapy for genital herpes in immunocompromised patients: a national survey. The
      Herpes Simplex Advisory Panel.
AB  - OBJECTIVES: To estimate the extent of aciclovir refractory herpes simplex virus
      (HSV) infection in HIV coinfected patients in the United Kingdom and survey
      clinicians on their approaches to its management. DESIGN: Questionnaire survey of
      representative sample of one third of United Kingdom HIV physicians. MAIN OUTCOME
      MEASURES: Use of antiviral therapies for genital HSV infections in HIV positive
      patients, reported frequency of aciclovir refractory HSV infection, its therapy,
      and access to antiviral susceptibility testing facilities. RESULTS: 53 responses
      were obtained (response rate 61%), representing a sample size of 23% of United
      Kingdom HIV physicians. Use of non-standard antiviral regimens for HSV infections
      in HIV coinfected patients was widely practised, irrespective of the clinical
      characteristics of the HSV infection. Aciclovir refractory HSV infection has been
      observed by 37 (70%) respondents. Although foscarnet was the most frequently used
      therapy, used by 27/37 (73%) respondents, in only seven of these 27 (19%) was it
      a first line treatment for aciclovir refractory cases, frequently being used at a
      late stage in the clinical course. Antiviral susceptibility testing facilities
      were available to 46 (87%) clinicians. No respondents reported any evidence of
      transmission of aciclovir resistant strains. CONCLUSIONS: HIV coinfection has a
      stronger influence on therapeutic choice than clinical immunosuppression or
      severity of herpetic infection. Aciclovir treatment failure is commoner than
      hitherto recognised. There is a need for wider awareness of use of foscarnet at
      an earlier stage in management of refractory HSV infection.

PMID- 9534752
TI  - Genital colonisation and infection with candida in heterosexual and homosexual
      males.
AB  - OBJECTIVES: To determine the penile, perianal, and oropharyngeal candidal
      colonisation rates among homosexual and heterosexual males attending an STD
      clinic. To determine the prevalence of balanitis and candidal balanitis in the
      two groups. SUBJECTS: 252 heterosexual and 210 homosexual male patients attending
      consecutively the STD clinic in Coventry, England. DESIGN: A prospective study
      recording sexual behaviour, relevant history, symptoms, and examination.
      Specimens for candida culture were collected from the glans penis, perianal area,
      and oropharynx. RESULTS: Among the 462 men studied, penile, perianal, and
      oropharyngeal colonisation rates were 74 (16%), 70 (15%), and 116 (25%)
      respectively. On examination, 47 (10%) were found to have balanitis. Of the 74
      patients with penile colonisation, 26 (37%) were symptomatic and 20 (27%) had
      balanitis. The 223 heterosexual and the 196 homosexual males who had sexual
      intercourse within 3 months had comparable colonisation rates of candida on the
      penis, perianal area, and oropharynx. Balanitis was seen in 31 heterosexuals
      (14%) and candidal balanitis in 16 (7%); the incidence was significantly less in
      homosexuals where balanitis was seen in 12 (6%) and candidal balanitis in four
      (2%). CONCLUSIONS: Itching or burning sensations after sex were the most common
      symptoms associated with penile colonisation with candida and were present in
      more than one third. Candidal balanitis was commoner in those who had vaginal
      than those who had anal intercourse within 3 months.

PMID- 9534753
TI  - Metronidazole resistant trichomoniasis successfully treated with paromomycin.
AB  - Management of a 42 year old female patient diagnosed with trichomoniasis is
      described. She failed to respond to recommended oral and high dose oral and
      topical metronidazole. Various options used in previously reported cases of
      metronidazole resistant trichomoniasis also failed to cure her condition. MIC
      showed the organism to be resistant to metronidazole. Cure was achieved with the
      use of topical intravaginal paromomycin.

PMID- 9534754
TI  - Lymphogranuloma venereum: biopsy, serology, and molecular biology.
AB  - A 21 year old woman presented with painful groin lymphadenopathy and malaise.
      Lymph node biopsy, to exclude atypical infection and malignancy, suggested the
      diagnosis of lymphogranuloma venereum. This diagnosis was confirmed by serology
      and polymerase chain reaction, with the patient subsequently admitting to a
      casual sexual contact within the United Kingdom. Alternative methods of
      investigation of this disease are discussed.

PMID- 9534755
TI  - Condylomata acuminata of the penis progressing rapidly to invasive squamous cell
      carcinoma.

PMID- 9534756
TI  - Why do homosexual men continue to practise unsafe sex? A critical review of a
      qualitative research paper.

PMID- 9534758
TI  - Genitourinary medicine and the Internet No 8.

PMID- 9534757
TI  - Haemolytic uraemic syndrome complicated by disseminated extraneural
      cryptococcosis.

PMID- 9534759
TI  - Medical Society for the Study of Venereal Disease seventy fifth spring meeting:
      Oxford 1997.

PMID- 9534760
TI  - Stavudine induced macrocytosis.

PMID- 9534761
TI  - Biopsy of male genital dermatosis.

PMID- 9534762
TI  - Characterisation of high level tetracycline resistant Neisseria gonorrhoeae
      isolates.

PMID- 9534763
TI  - Epidemiology of genital Chlamydia trachomatis.

PMID- 9534764
TI  - [Experiences of a veterinary meat inspector. I].
AB  - Re-inspection of animals for slaughter is based on article 13 of the Meat
      Inspection Act, under which re-inspection is defined as a new inspection. This
      article describes the re-inspection of 94 animals for slaughter according to
      existing regulations and instructions. In 45% of the cases, the veterinary meat
      inspector had doubts about the decisions taken in the first inspection or about
      the grounds mentioned as reason for the decision to reject or condemn the
      animal/carcass. The verdict of the first inspection was changed when there were
      positive results for tests for agents that slow bacterial growth, positive
      results for tests for bacteria, abnormal consistency, and cysticercosis. It was
      concluded that, in the interests of uniformity all the investigations stipulated
      in the Inspection Regulations should be carried out during the first inspection
      and that all reasons for condemning an animal/carcass should be given. In
      addition, all veterinary meat inspectors involved should be told the outcome of
      the second inspection and of any omissions discovered during this inspection.

PMID- 9534765
TI  - [Experiences of a veterinary meat inspector. II].
AB  - A number of unusual or repeat inspections are described. These inspections took
      place in relation to investigations for the presence of agents that slow
      bacterial growth (New Netherlands Kidney Test), condemnation of the
      animal/carcass for more than one reason, investigations to detect the presence of
      hormones and beta-antagonists, severe abscesses in the spleen, absence of the
      entire carcass, special emergency slaughter, deep cuts in the kidney, and
      botulism. Emphasis is placed on the importance of veterinary meat inspectors
      being closely involved in the rejection or condemnation of animals for slaughter.

PMID- 9534766
TI  - [Evaluation of hip dysplasia admissions].

PMID- 9534767
TI  - [Respiratory symptoms in meat pigs: is there a role for porcine respiratory
      corona virus (PRCV) and porcine reproductive and respiratory syndrome virus
      (PRRSV) in the etiology?].
AB  - On a pig farm with about 2000 pigs, respiratory problems regularly developed in
      fattening pigs 3 to 4 weeks after the start of the fattening period. A postmortem
      examination was carried out on four pigs during the acute phase of their illness.
      The animals showed signs of viral pneumonia. In two animals porcine respiratory
      virus (PRCV) was discovered and in the other two animals porcine reproductive and
      respiratory syndrome virus (PRRSV). The possible role of these two viruses in the
      aetiology of the health problems on this farm is discussed in the context of the
      results of a longitudinal serological study.

PMID- 9534768
TI  - [Salmonella typhimurium DT104, also in The Netherlands?].

PMID- 9534769
TI  - [Hog cholera epidemic].

PMID- 9534770
TI  - [Does 'borreliosis in dogs' exist?].

PMID- 9534771
TI  - [Neospora abortion in cattle].

PMID- 9534772
TI  - [Anticoagulant rodenticide poisoning in dogs in The Netherlands].
AB  - The occurrence, the diagnosis, and the treatment of anticoagulant rodenticide
      poisoning in dogs in the Netherlands was evaluated by a survey among Dutch
      veterinarians carried out by the National Poisons Control Center (NPCC). The
      survey included information on 54 dogs, 32 being treated by veterinarians who
      consulted the NPCC and 22 that were admitted to the Utrecht University Clinic for
      Companion Animals (UUCCA). The poisons that were suspected were brodifacoum (n =
      19), bromadiolone (n = 14), difenacoum (n = 8), difethialone (n = 6) and
      chlorophacinone (n = 1). In 6 dogs the identity of the poison was unknown. Of 31
      dogs with hemorrhages, 2 died shortly after presentation to practitioners and 2
      died shortly after admission to the UUCCA. Signs of bleeding occurred especially
      in poisoning by brodifacoum (n = 16). In all but one of the dogs without
      hemorrhages, the intake of poison had taken place within 24 hours before
      presentation. The method of treatment varied, with the induction of vomiting and
      the use of vitamin K mentioned most. The choice of therapy was determined by the
      length of time after intake of the poison, the clinical signs and whether or not
      an anticoagulant toxicosis was suspected at the time of the initial examination.
      These findings provide the basis for discussion of several aspects of diagnosis
      and treatment.

PMID- 9534773
TI  - [Pioneers: veterinarians from an earlier time (23). Johann Adam Kersting (1727
      1784)].

PMID- 9534774
TI  - [Tracing of hog cholera].

PMID- 9534776
TI  - [Genetic and epidemiological studies in boxers. Current status].

PMID- 9534777
TI  - [RVV (National Service for Inspection of Cattle and Meat): hygiene measures of
      veterinarians variable. Limiting risks of practice visits through intervision].

PMID- 9534779
TI  - [Round-table GPGH (Group Practitioners Large Domestic Animals): education in
      veterinary medicine. General practice sore point for practitioners].

PMID- 9534778
TI  - [Ambitious plan for sector companion animals. Establishment Foundation
      Vaccination Companion Animals].

PMID- 9534780
TI  - [4 unusual cases of malignant lymphoma in the dog and cat].
AB  - Malignant Lymphoma is a common tumour disease in dogs and cats. In the dog
      lymphoma's are predominantly multicentric, while in the cat lymphoma's are mainly
      found in the mediastinum and intestinal tract. This article describes four cases
      of lymphoma found in unusual locations. Chemotherapy is briefly discussed.

PMID- 9534781
TI  - [Resolution prohibited agents veterinary drug law. Limited use of growth
      promoting hormones and beta-agonists].

PMID- 9534782
TI  - [Campaign against hog cholera: some marginal notes].

PMID- 9534783
TI  - [Evaluation of hip dysplasia radiographic images].

PMID- 9534786
TI  - [A closer look at the milking machine].
AB  - Machine milking has changed enormously in the past decades. The simple milking
      machine developed at the end of the nineteenth century has become a complex
      appliance which removes milk from the udder in a fast and efficient way. There is
      no doubt about the importance of a well functioning milking machine as regards
      milk quality and udder health. This article reviews the literature on the basic
      mechanics of machine milking, with special emphasis on the action of the cluster
      during milking. The movement of the teat cup liner is particularly important in
      influencing the efficiency of milk extraction and udder health. Therefore special
      attention is paid to the operation of the liner, how it works, and how the
      opening and closing of the liner affects the milking process. The functioning of
      the pulsator, the vacuum fluctuations occurring during milking, and the effect of
      these fluctuations on the opening and closing of the liner are discussed. The
      maintenance of the milking machine is also described.

PMID- 9534787
TI  - [Farewell of a many-sided scientist: Dr. C. Terpstra: 'What is the benefit for
      clinical practice?'].

PMID- 9534788
TI  - [Mastitis Panel meeting 14 May 1997. Treatment of subclinical mastitis during
      lactation].

PMID- 9534790
TI  - [Canis familiaris: an endangered species in The Netherlands].

PMID- 9534791
TI  - [Reaction KNMvD to LNV memo 'Structural changes in pig farming' (Royal Dutch
      Society for Veterinary Medicine) (Ministry of Agriculture Nature Conservation and
      Fishery)].

PMID- 9534792
TI  - [Machine milking and udder health: a literature review].
AB  - This article reviews the influence of machine milking on udder health. The main
      risks are transmission and penetration of pathogens during milking. Pathogens can
      be transmitted via the hands, cloths, and liners. Irregular fluctuations in the
      vacuum can cause penetration of mastitis pathogens into or through the teat
      canal. Such fluctuations are caused by air blasts in the milking machine. Machine
      milking can also cause teat lesions, although only severe lesions give rise to
      new infections. Preliminary research results on the influence of the frequency
      and degree of udder evacuation show that the clinical symptoms of mastitis
      generally decreases as the frequency and completeness of milking increase. It is
      concluded that machine milking can influence udder health but that the influence
      strongly depends on the exposure to pathogens and the quality of the milker.

PMID- 9534794
TI  - [Euthanasia of very young piglets to be stopped on October 20].

PMID- 9534795
TI  - [Severe watery diarrhea caused by Vibrio cholerae in lambs].
AB  - An outbreak of watery diarrhoea in lambs is described. Seventeen lambs died
      within 24 hours after the start of the diarrhoea. At necropsy Vibrio cholerae was
      isolated from the organs and intestines of three lambs. The strains did not react
      with O1 or O139 antisera, the strains responsible for cholera epidemics among
      humans. It is concluded that the diarrhoea in the lambs was caused by V. cholerae
      non-01/non-139. This microorganism had not been described before in lambs in the
      Netherlands.

PMID- 9534798
TI  - [Pigs as source animals for humans].
AB  - This article reviews the current status of animal-to-human organ transplantation
      (xenotransplantion). In addition to immunological problems and the risk of
      disease, ethical issues with regard to both donor animals and humans make this
      technique not yet practicable. From further progress of this essentially
      veterinary development veterinary medicine and research will benefit.

PMID- 9534796
TI  - [Epidemic of nutritional polyneuropathy in the cat. Final report of the
      investigational team].
AB  - In June 1996 companion animal practitioners received a report prepared by the
      Faculty Investigative Team on the outbreak of polyneuropathy among cats, and at
      the end of August a 'definitive' bulletin was circulated by Spillers Petfoods.
      The coccidiostatic drug salinomycin, which was present in the vitamin premix
      supplied by a third party, was considered the cause of the neuropathy. The
      investigative team is of the opinion that all veterinary practitioners in the
      Netherlands should receive a conclusive report about the epidemic because of the
      unique nature of the epidemic, which despite its sudden outbreak could be well
      documented, and because aspects of the affair merit the attention of veterinary
      practitioners.

PMID- 9534800
TI  - [Seminar multi-site systems in pig farming].

PMID- 9534801
TI  - [Tracing of hog cholera].

PMID- 9534803
TI  - [Veterinary dentistry (14). Periapical diseases].
AB  - In this article periapical disease is discussed. A differentiation is made in
      infections, abscesses, granuloma and cysts.

PMID- 9534804
TI  - [Veterinary dentistry (15). Apex resection in the horse].
AB  - Periapical disorders in horses can be treated by resection of the apex. The
      indications, contraindications, diagnosis, treatment and complications of the
      intervention are discussed. Four case reports of horses in which apicoectomy with
      retrograde endodontic treatment was performed are reviewed.

PMID- 9534805
TI  - [More than 1 million food infections per year. 'Mistakes' in housekeeping cause
      in half of the cases].

PMID- 9534807
TI  - [Legal status of animals and of the veterinarian: a minefield?].

PMID- 9534806
TI  - [Hearing on the structure of Dutch pig farming. Royal Dutch Veterinary Society
      consults with Lower Chamber].

PMID- 9534808
TI  - [Trends in veterinary tools].

PMID- 9534809
TI  - [The pharmacy in companion animal practice].

PMID- 9534810
TI  - [Vaccination and vaccination policy--a future perspective].

PMID- 9534811
TI  - [Atopic dermatitis in dogs and cats].

PMID- 9534812
TI  - [Initial approach to thoracic injuries].

PMID- 9534813
TI  - [The diagnosis of kidney diseases].

PMID- 9534814
TI  - [Value of arthroscopy in the diagnosis and treatment of osteochondrosis in dogs].

PMID- 9534815
TI  - [Approach to nasal aspergillosis].

PMID- 9534817
TI  - [No proof that antibiotics resistance is transmitted from animal to human].

PMID- 9534816
TI  - [Splenic tumors: OK or not OK?].

PMID- 9534818
TI  - [Antibiotics: medicines or hog food?].

PMID- 9534819
TI  - [Prof. H.C. Marian C. Horzinek speaks--'every change... has immunological
      consequences. Interview by Sophie Deleu].

PMID- 9534820
TI  - New arrangements for processing notifications of infectious disease returns.

PMID- 9534821
TI  - AIDS and HIV infection in the United Kingdom: monthly report.

PMID- 9534822
TI  - Cost-effective or profligate community psychiatry?

PMID- 9534823
TI  - Contracting in mental health.

PMID- 9534824
TI  - Analysis of longitudinal data. Beyond MANOVA.
AB  - BACKGROUND: Longitudinal data arise frequently in psychiatric investigations, and
      are most often analysed by multivariate analysis of variance (MANOVA) procedures.
      However, as routinely applied, the method is not satisfactory, particularly when
      the data are affected by subjects dropping-out of the study. More suitable
      methods are now available. METHOD: Problems with the MANOVA approach are
      discussed and the advantages of alternative procedures stressed. RESULTS: Using
      MANOVA on complete cases to analyse unbalanced longitudinal data can be seriously
      misleading. More recently developed methods are far more suitable, but only if
      the missing values are non-informative. CONCLUSIONS: Routine use of MANOVA for
      the analysis of longitudinal data, particularly when there is a substantial
      proportion of drop-outs, is ill advised. Statisticians have considerably enriched
      the available methodologies during the past decade, and psychiatric researchers
      dealing with such data should be aware of the advantages of the newer methods.

PMID- 9534825
TI  - Health of the Nation Outcome Scales (HoNOS). Research and development.
AB  - BACKGROUND: An instrument was required to quantify and thus potentially measure
      progress towards a Health of the Nation target, set by the Department of Health,
      "to improve significantly the health and social functioning of mentally ill
      people". METHOD: A first draft was created in consultation with experts and on
      the basis of literature review. This version was improved during four stages of
      testing: two preliminary stages, a large field trial involving 2706 patients
      (rated by 492 clinicians) and tests of the final Health of the Nation Outcome
      Scales (HoNOS), which included an independent study (n = 197) of reliability and
      relationship to other instruments. RESULTS: The resulting 12-item instrument is
      simple to use, covers clinical problems and social functioning with reasonable
      adequacy, has been generally acceptable to clinicians who have used it, is
      sensitive to change or the lack of it, showed good reliability in independent
      trials and compared reasonably well with equivalent items in the Brief
      Psychiatric Rating Scales and Role Functioning Scales. CONCLUSIONS: The key test
      for HoNOS is that clinicians should want to use it for their own purposes. In
      general, it has passed that test. A further possibility, that HoNOS data
      collected routinely as part of a minimum data set, for example for the Care
      Programme Approach, could also be useful in anonymized and aggregated form for
      public health purposes, is therefore testable but has not yet been tested.

PMID- 9534827
TI  - Recurrence in affective disorder. I. Case register study.
AB  - BACKGROUND: In recent years, studies of the risk of recurrence in affective
      disorder in relation to the number of prior episodes have given contradictory
      results. METHOD: Survival analysis was used to calculate the rate of recurrence
      after successive episodes in a case register study including all hospital
      admissions with primary affective disorder in Denmark during 1971-1993. A total
      of 20,350 first-admission patients were discharged with a diagnosis of affective
      disorder, depressive or manic/cyclic type. RESULTS: The rate of recurrence
      increased with the number of previous episodes in both unipolar and bipolar
      disorder. Initially, the two types of disorders followed markedly different
      courses, but later in the course of the illness the rate of recurrence was the
      same for the two disorders. CONCLUSIONS: The course of severe unipolar and
      bipolar disorder seems to be progressive in nature despite the effect of
      treatment.

PMID- 9534826
TI  - Intensive case management for the severely mentally ill. Controlled trial.
AB  - BACKGROUND: The aim was to compare the efficacy of intensive clinical case
      management (ICM) with standard community care in the management of 'hard to
      treat' patients with a severe mental illness. METHOD: A randomised controlled
      trial was carried out in East Lambeth, a deprived area of inner London. Seventy
      people with psychosis designated as 'hard to treat' by referring teams were
      included; 35 were randomised to ICM (case load eight patients per worker), and 35
      to standard care, which offered follow-up by a community psychiatric nursing
      service (30 patients per worker). Outcome measures were admissions and hospital
      bed utilisation; contact with services; symptomatology; social behaviour; social
      functioning; quality of life; patients' satisfaction with care at 9 and 18
      months. RESULTS: There were no differences in patients' symptoms, social
      behaviour or social functioning. Quality of life was significantly improved in
      patients receiving ICM at 9 months. Satisfaction with care was significantly
      greater among case-managed patients. All ICM patients remained in contact with
      services throughout the study, while six control patients were refusing all
      contact with services at 18 months. CONCLUSIONS: ICM failed to improve the
      clinical outcome of 'hard to treat' patients. The service was successful in
      maintaining contact with patients, was greatly appreciated and had a positive
      effect on their perceived quality of life.

PMID- 9534828
TI  - Recurrence in affective disorder. II. Effect of age and gender.
AB  - BACKGROUND: The risk of recurrence in affective disorder has been found to
      increase with each new episode. It is unclear whether it is universal without
      regard to gender, age and type of disorder. METHOD: Survival analysis was used to
      estimate the risk of recurrence in a case-register study including all hospital
      admissions with primary affective disorder in Denmark from 1971-1993. In this
      period 20,350 first-admission patients had been discharged with a diagnosis of
      affective disorder, depressive or manic/cyclic type. RESULTS: The risk of
      recurrence increased with the number of previous episodes regardless of the
      combination of gender, age and type of disorder. Initially in the course of
      illness, unipolar and bipolar women experienced an equal greater risk of
      recurrence than men. The risk of recurrence after the first episode was increased
      for middle-aged and older unipolar women compared with the risk for younger
      women, while after all other episodes younger age at first episode increased the
      risk of recurrence. CONCLUSIONS: The course of severe unipolar and bipolar
      disorder seems to be progressive in nature irrespective of gender, age and type
      of disorder.

PMID- 9534829
TI  - Lifetime risk of suicide for affective disorder, alcoholism and schizophrenia.
AB  - BACKGROUND: The lifetime risks of suicide are generally quoted as 15% for
      affective disorder and alcoholism and 10% for schizophrenia, based on data from
      1921-1975 and on calculations performed before computerised modelling techniques
      became available. This study recalculates the risk using contemporary data and
      modern techniques. METHOD: Twenty-seven mortality studies provided data for
      affective disorder, 27 for alcohol dependence and 29 for schizophrenia. The
      proportion of the cohort who had died was plotted against the proportion of
      deaths from suicide. Modelling techniques fitted curves through the data points
      extrapolating them to cohort extinction, thus estimating the lifetime risk of
      suicide for each disorder. RESULTS: The lifetime risk was estimated at 6% for
      affective disorder. 7% for alcohol dependence and 4% for schizophrenia.
      CONCLUSIONS: The lifetime suicide risk figures often quoted in the literature
      appear to be too high.

PMID- 9534830
TI  - Prospective study into factors associated with aggressive incidents in
      psychiatric acute admission wards.
AB  - BACKGROUND: Factors associated with aggression among psychiatric in-patients are
      still poorly understood. Inconsistent published findings are partly attributable
      to methodological problems. Much previous research has been under taken in
      specialist settings, where conditions are likely to differ from those in acute
      admission wards. METHOD: Levels of aggression were ascertained weekly by staff
      report, using a reliable measure, for every patient on five acute admission wards
      and one locked intensive care ward at two hospitals prospectively over a five
      month period. RESULTS: Levels of aggression varied considerably among the
      admission wards. Aggression was more common on the locked ward and among younger
      patients. Factors associated with aggression changed with time since admission
      (seldom examined in previous studies). Complex associations were found with
      gender, ethnic group and diagnosis. CONCLUSIONS: Some of the findings might be
      explicable by differences in ward environment, and staff-patient inter-actions.
      Further investigation into these is warranted.

PMID- 9534831
TI  - Cost and benefit in the choice of ECT schedule. Twice versus three times weekly
      ECT.
AB  - BACKGROUND: We compared the antidepressant and cognitive effects of up to eight
      sessions of bilateral, brief pulse electroconvulsive therapy (ECT) administered
      twice (ECT x 2) or three times weekly (ECT x 3), to confirm that ECT x 3 acts
      more rapidly although the two schedules are equivalent in antidepressant outcome,
      and to establish whether ECT x 3 is indeed associated with more severe memory
      impairment. METHOD: Patients with major depression, endogenous subtype were
      randomly assigned to ECT x 3 or ECT x 2 plus one simulated ECT per week, both up
      to a maximum of eight real ECT. Depression was evaluated by the Hamilton
      Depression Scale the day after each treatment and cognitive function by a test
      battery administered before and after the ECT series and at one month follow-up.
      RESULTS: Assessed categorically or parametrically, there was no significant
      difference in antidepressant outcome between the two schedules. Rate of response
      was significantly more rapid with ECT x 3 but was associated with more severe
      memory impairment. CONCLUSIONS: Twice weekly administration is an optimum
      schedule for bilateral ECT unless clinical indications require the more rapid
      antidepressant effect of three times weekly treatment.

PMID- 9534832
TI  - Brain 5-HT neurotransmission during paroxetine treatment.
AB  - BACKGROUND: Animal experimental studies suggest that repeated administration of
      selective serotonin reuptake inhibitors (SSRIs) produces complex adaptive changes
      in brain serotonin (5-HT) pathways. The effect of these adaptive changes on
      different aspects of brain 5-HT neurotransmission and their clinical consequences
      are not well understood. METHOD: We studied the effect of repeated administration
      of the SSRI, paroxetine (20 mg daily), on the cortisol responses to the 5-HT
      precursor, 5-hydroxytryptophan (5-HTP), in healthy subjects and depressed
      patients. RESULTS: In healthy subjects, following one week of paroxetine
      treatment there was a large increase in the cortisol response to 5-HTP. This
      increase had all but disappeared following 3 weeks treatment. In contrast, in
      depressed patients treated with paroxetine for 8 weeks, the cortisol response to
      5-HTP was significantly increased. CONCLUSIONS: SSRI treatment in depressed
      patients produces a persistent increase in the cortisol response to 5-HTP, a
      probable measure of neurotransmission at central 5-HT2 receptors. Potentiation of
      5-HT2 neurotransmission is unlikely to account for the efficacy of SSRIs in major
      depression but might underlie their actions in obsessive-compulsive disorder and
      also perhaps certain of their adverse effects, notably sexual dysfunction.

PMID- 9534833
TI  - Outcome of common mental disorders in Harare, Zimbabwe.
AB  - BACKGROUND: Little is known about the outcome of common mental disorders (CMD) in
      primary care attenders in low income countries. METHOD: Two and 12 month (T1 and
      T2) follow-up of a cohort of cases of CMD (n = 199) recruited from primary
      health, traditional medical practitioner, and general practitioner clinics in
      Harare, Zimbabwe. The Shona Symptom Questionnaire (SSQ) was the measure of
      caseness. RESULTS: The persistence of case level morbidity was recorded in 41% of
      subjects at 12 months. Of the 134 subjects interviewed at both follow-up points,
      49% had recovered by T1 and remained well at T2 while 28% were persistent cases
      at both T1 and T2. Higher SSQ scores, a psychological illness model, bereavement
      and disability predicted a poor outcome at both times. Poorer outcome at T1 only
      was associated with a causal model of witch-craft and an unhappy childhood.
      Caseness at follow-up was associated with disability and economic deprivation.
      CONCLUSIONS: A quarter of cases of CMD were likely to be ill throughout the 12
      month follow-up period. Targeting risk groups for poor outcome for interventions
      and policy interventions to reduce the impact of economic deprivation may provide
      a way of tackling CMD in primary care in low income countries.

PMID- 9534834
TI  - Effects of postnatal depression on children's adjustment to school. Teacher's
      reports.
AB  - BACKGROUND: Little is known of the behavioural adjustment of children of
      postnatally depressed mothers. Previous studies have relied on maternal reports,
      and have produced inconsistent findings. METHOD: In a prospective, longitudinal
      study of the five-year-old children of a community sample of postnatally
      depressed and well women, evidence was collected concerning the children's
      adjustment in the context of school, teachers being asked to complete
      questionnaires after the children had finished their first term. RESULTS: Family
      social class and the child's gender had the most pervasive influences on
      adjustment. However, both postnatal and recent maternal depression were
      associated with significantly raised levels of child disturbance, particularly
      among boys and those from lower social class families. CONCLUSIONS: The findings
      indicate a persistent effect of postnatal depression on child adjustment. They
      highlight the need for resources devoted to supporting mothers of young children
      and particularly routine screening and treatment for postnatal mood disorder.

PMID- 9534835
TI  - Psychiatric staff as attachment figures. Understanding management problems in
      psychiatric services in the light of attachment theory.
AB  - BACKGROUND: Attachment theory argues that psychological development and
      functioning are affected by our earliest attachments to care-givers. Failed or
      pathological attachment in childhood may give rise to repetition of maladaptive
      attachment patterns in adulthood. METHOD: Analysis of therapeutic relationships
      in the light of attachment theory. RESULTS: Relationships between patients and
      both psychiatric care-givers and institutions may resemble attachment
      relationship. CONCLUSION: An attachment perspective may be useful for
      understanding common behavioural disturbances in general psychiatric settings,
      and support the use of clinical strategies which focus on containment of arousal
      and the management of anxiety states.

PMID- 9534836
TI  - Placebo-controlled trial of moclobemide in social phobia.
AB  - BACKGROUND: Moclobemide, a reversible inhibitor of monoamine oxidase A,
      previously has been reported to have efficacy in the treatment of social phobia.
      METHOD: Seventy-seven non-responders to one week of single-blind placebo were
      randomly assigned to moclobemide or placebo for eight weeks of double-blind
      treatment. Outcome was assessed by independent evaluator, treating psychiatrist
      and self-ratings. After eight weeks, patients who were at least minimally
      improved continued treatment for a further eight weeks. RESULTS: Intention-to
      treat sample response rates at week 8 were 7/40 (17.5%) for the moclobemide group
      and 5/37 (13.5%) for placebo (NS). Moclobemide was significantly superior to
      placebo on 2 of 10 primary outcome measures. Moclobemide was well tolerated.
      CONCLUSIONS: Moclobemide may have efficacy in the treatment of social phobia, but
      absence of significant differences on most primary outcome measures and small
      effect sizes for all outcome measures suggest that the magnitude of its clinical
      effect is small.

PMID- 9534837
TI  - Informing patients about tardive dyskinesia. Controlled trial of patient
      education.
AB  - BACKGROUND: This paper evaluates the effects on knowledge and clinical stability
      of an educational intervention about tardive dyskinesia. METHOD: Fifty-six
      patients receiving antipsychotic maintenance completed a questionnaire assessing
      their knowledge about tardive dyskinesia. After random allocation to either an
      educational intervention or a control group, their knowledge was reassessed at
      six months. RESULTS: Ninety-five per cent of patients completed the study. The
      study patients gained significantly more knowledge than the controls, who made
      modest gains. There were no significant differences in clinical outcome between
      the groups. CONCLUSION: Patients can learn about serious toxic effects of
      antipsychotic treatment with a low risk of non-compliance. Discussion about
      tardive dyskinesia is necessary in the process of obtaining informed consent to
      treatment.

PMID- 9534838
TI  - Treatment of severe clozapine-induced neutropenia with granulocyte colony
      stimulating factor (G-CSF). Remission despite continuous treatment with
      clozapine.
AB  - BACKGROUND: A 17-year-old boy suffering from a severe schizophrenic disorder of
      the paranoid type and mental retardation did not respond to treatment with
      typical antipsychotics, whereas under clozapine treatment he showed a favourable
      response. Discontinuation of clozapine led to an acute psychotic relapse. During
      clozapine treatment the patient developed severe neutropenia. METHOD AND RESULTS:
      Due to the history of unsatisfactory response to traditional antipsychotics,
      clozapine treatment was continued despite white blood cell (WBC) decline.
      Concomitant treatment with G-CSF was followed by a rapid normalisation of WBC.
      CONCLUSIONS: This case report is not intended to challenge the clinical practice
      of discontinuing clozapine upon the development of neutropenia/agranulocytosis,
      but rather to stimulate further research in the pathophysiology and clinical
      consequences of a clozapine rechallenge after a WBC decline, especially in
      patients with a rather complex symptomatology where no sufficient therapeutic
      results can be achieved with any other pharmacological intervention than
      clozapine.

PMID- 9534839
TI  - Behaviour phenotype for Down's syndrome.
AB  - BACKGROUND: For more than a century, the idea of particular
      personality/behavioural characteristics being associated with people with Down's
      syndrome has been explored, but with inconclusive results. METHOD: The Disability
      Assessment Schedule was used to ascertain the behavioural profiles of 360 adults
      with Down's syndrome and 1829 adults with learning disabilities of other
      aetiologies, who were the whole identified population within a defined
      geographical area. Comparison was made between the two total groups and
      additionally for the subgroups aged < 35 years and aged > or = 35 years.
      Comparison was also made with regards to cluster analysis findings. RESULTS:
      Despite an equal age and developmental quotient, the Down's syndrome group were
      less likely to demonstrate maladaptive behaviours. The behaviour characteristics
      of the adults with Down's syndrome remained constant in the younger and older age
      groups. Cluster analysis demonstrated adults with Down's syndrome to have an
      increased prevalence in cluster groupings with lower rates of maladaptive
      behaviours. CONCLUSIONS: This study confirms there to be a behaviour phenotype
      among adults with Down's syndrome. The reasons for this (e.g.
      genetic/psychological/social) require further research. Such research may
      establish a better understanding of the aetiologies of maladaptive behaviours
      among people with learning disabilities in general.

PMID- 9534840
TI  - Psychological sequelae of torture and organised violence suffered by refugees
      from Iraq. Trauma-related factors compared with social factors in exile.
AB  - BACKGROUND: Refugees who have suffered traumatic events present complex
      therapeutic challenges to health professionals. There is little research into
      post-exile factors that may be amenable to change, and therefore reduce
      morbidity. We examined the importance of social factors in exile and of trauma
      factors in producing the different elements of psychological sequelae of severe
      trauma. METHOD: Eighty-four male Iraqi refugees were interviewed. Adverse events
      and level of social support were measured. Various measures of psychological
      morbidity were applied, all of which have been used in previous trauma research.
      RESULTS: Social factors in exile, particularly the level of "affective" social
      support, proved important in determining the severity of both post-traumatic
      stress disorder and depressive reactions, particularly when combined with a
      severe level of trauma/torture. Poor social support is a stronger predictor of
      depressive morbidity than trauma factors. CONCLUSIONS: Some of the most important
      factors in producing psychological morbidity in refugees may be alleviated by
      planned, integrated rehabilitation programmes and attention to social support and
      family reunion.

PMID- 9534841
TI  - Psychiatrists' dress and address.

PMID- 9534842
TI  - Psychiatrists' dress and address.

PMID- 9534843
TI  - Ethnicity and dissatisfaction with mental health services.

PMID- 9534844
TI  - Subjective memory complaints, depression and dementia.

PMID- 9534845
TI  - Lithium withdrawal mania supports lithium's antimanic action and suggests an
      animal model involving serotonin.

PMID- 9534846
TI  - Ethnicity and clozapine metabolism.

PMID- 9534847
TI  - Soft tissues, hard times: a mordant affair.

PMID- 9534848
TI  - Hypercalcemia and metastatic calcification.

PMID- 9534849
TI  - The new ischemic syndromes--an old phenomenon disguised with a new glossary?

PMID- 9534850
TI  - 'Myocardial hibernation'--questions and controversies.

PMID- 9534851
TI  - Signal transduction revisited: recent developments in angiotensin II signaling in
      the cardiovascular system.

PMID- 9534852
TI  - Evaluation of myocardial ischemia in Kawasaki disease by dobutamine stress signal
      averaged ventricular late potentials.
AB  - OBJECTIVE: To determine the possibility of diagnosing myocardial ischemia from
      signal-averaged electrocardiographic late potentials (LPs) in patients with
      Kawasaki disease. METHODS: Dobutamine stress LPs were obtained in 85 children
      with a history of Kawasaki disease (48 without coronary artery lesions, 19 with
      coronary artery lesions without myocardial ischemia, and 18 with myocardial
      ischemia). The infusion of dobutamine was started at 5 micrograms/kg/min,
      increased to 30 micrograms/kg/min. The presence of LPs was determined by the
      filtered QRS duration, the root mean square voltage during the last 40 ms, and
      the duration of the signal under 40 microV. RESULTS: Among the children without
      coronary lesions, LPs were detected in 4.2% at rest and in 2.1% with dobutamine
      stress. Among the group with coronary lesions but without ischemia, LPs were
      found in 5.3% at rest and in 5.3% with stress. In the group with ischemia, LPs
      were present in 44.4% at rest and in 77.8% with stress. The sensitivity for
      myocardial ischemia was 72.7% at rest and 87.5% with stress (p < 0.05), and the
      specificity was 86.5% at rest and 94.2% with stress. CONCLUSION: LPs associated
      with dobutamine stress testing are useful for identifying myocardial ischemia in
      children with Kawasaki disease, especially in those who cannot tolerate testing
      involving physical exercise.

PMID- 9534853
TI  - Is oxidative stress causally linked to unstable angina pectoris? A study in 100
      CAD patients and matched controls.
AB  - OBJECTIVE: Unstable angina pectoris often leads to acute myocardial infarction.
      Since lipid peroxidation is thought to be causally related to chronic and acute
      events in atherosclerosis and coronary artery disease, we measured lipid
      peroxidation products and vitamin E in 100 patients with coronary artery disease
      and compared them to a matched control group. METHODS: 50 consecutive patients
      with stable angina pectoris (SAP) and 50 consecutive patients with unstable
      angina pectoris (UAP) were studied and compared to 100 clinically healthy
      individuals. In addition to conventional lipid and lipoprotein analysis,
      malondialdehydes were measured as thiobarbituric acid reactive substances
      (TBARS). Lipid hydroperoxides were assayed with the colorimetric methylene blue
      method. alpha-Tocopherol was quantitated by HPLC after extraction of serum with
      hexane-ethanol. In the patient group conjugated dienes were also measured.
      RESULTS: As expected, patients had significantly higher cholesterol, triglyceride
      LDL-C and Lp(a) values and lower HDL-C values than controls. When patients were
      divided into groups with SAP and UAP respectively, peroxides and TBARS were
      significantly higher in the latter group as compared to patients with SAP and to
      controls. Conjugated dienes were also significantly higher in patients with UAP
      as compared to patients with SAP. Total plasma alpha-tocopherol was comparable in
      all three groups, whereas the alpha-tocopherol content per LDL particle was
      lowest in patients with UAP, followed by patients with SAP and then controls.
      CONCLUSION: It is concluded that lipid peroxidation parameters are increased in
      patients with UAP and discriminate SAP from UAP patients.

PMID- 9534854
TI  - Differential roles of myocardial Ca2+ channels and Na+/Ca2+ exchange in
      myocardial reperfusion injury in open chest dogs: relative roles during ischemia
      and reperfusion.
AB  - OBJECTIVE: Compare the roles of Ca2+ channels and Na+/Ca2+ exchange in
      reperfusion injury (reperfusion ventricular fibrillation and myocardial
      stunning). METHODS: Open chest dogs undergoing 15 minutes of left anterior
      descending coronary artery occlusion and 3 hours of reperfusion were randomized
      to controls or intracoronary infusions of the respective antagonists, nifedipine
      (50 micrograms/min) or amiloride (5 mg/min), according to five protocols: (A) 40
      minutes before occlusion to 30 minutes after reperfusion; (B) 2 minutes before to
      5 minutes after reperfusion; (C) 10 minutes before to 10 minutes after
      reperfusion (two step infusion for nifedipine only 5 micrograms/min during
      occlusion and 50 micrograms/min after reperfusion); and (D) 0 to 30 minutes after
      reperfusion. The role of Ca2+ channels was further investigated by infusing the
      agonist, Bay K 8644 (50 micrograms/min), alone or simultaneously with any
      protocol B, C, or D infusions altering both reperfusion ventricular fibrillation
      and myocardial stunning. RESULTS: Effects of the agents on injury did not result
      from hemodynamic effects or alterations in blood flow. Amiloride had no effect on
      ventricular fibrillation. Only protocol A infusion of amiloride prevented
      myocardial stunning. In contrast, protocol A and B infusions of nifedipine
      prevented both myocardial stunning (p = ns vs. baseline, p < 0.01 vs. control)
      and ventricular fibrillation (0%, p < 0.01). Protocol C prevented reperfusion
      ventricular fibrillation, but not stunning (p = ns vs. control). Protocol D did
      not alter injury. Bay K 8644 co-treatment reversed the effects of Protocol B
      infusion of nifedipine. Ventricular fibrillation was common and postischemic
      function worst in dogs treated with Bay K 8644 alone (protocol B). CONCLUSION:
      Myocardial Ca2+ channels contribute to both reperfusion ventricular fibrillation
      and stunning, whereas Na+/Ca2+ exchange contributes only to stunning. Inhibitors
      of myocardial Ca2+ channels are protective when infused in high doses just before
      reperfusion, whereas the efficacy of Na+/Ca2+ exchange inhibitors is dependent on
      pretreatment.

PMID- 9534855
TI  - The effect of delayed reperfusion following infarction in the rat on structural
      changes in viable myocardium.
AB  - OBJECTIVE: Evidence indicates that patency of the infarct related artery
      following the completion of myocardial necrosis can attenuate ventricular
      remodeling. Data have also demonstrated that inhibition of infarct expansion
      contributes to the anti-remodeling effect of delayed reperfusion. However, the
      influence of a patent artery on components of the remodeling process in the
      viable myocardium is poorly understood. METHODS: Myocyte morphometrics (isolated
      cell technique) and collagen content (hydroxyproline analysis) were assessed 28
      days following experimental myocardial infarction from rats with permanently
      ligated left coronary vessels (NRP; n = 10) compared with rats who underwent
      reperfusion 150 minutes after ligation (RP; n = 11) and a sham-operated group (n
      = 10). RESULTS: Analysis of infarct size (planimetry) in a separate group of rats
      demonstrated that reperfusion at this late time point did not reduce infarct size
      (NRP: 33 +/- 3 vs. RP: 35 +/- 5%). Myocyte length in RP rats was less than in NRP
      rats in viable, non-infarcted left ventricular tissue (155 +/- 3 vs. 167 +/- 4
      microns, p = 0.02), in the right ventricle (154 +/- 4 vs. 167 +/- 3 microns, p =
      0.02) and in the septum (158 +/- 4 vs. 169 +/- 4 microns, p = 0.05). Reperfusion
      also attenuated the expected increase in cell volume compared with NRP rats (left
      ventricle 39.4 +/- 1.7 x 10(3) vs. 44.1 +/- 1.6 x 10(3) micron 3, p = 0.06; right
      ventricle 36.7 +/- 1.6 x 10(3) vs. 42.7 +/- 2.0 x 10(3) micron 3, p = 0.02;
      septum 41.0 +/- 1.6 x 10(3) vs. 44.2 +/- 1.8 x 10(3) micron 3, p = 0.19).
      Hydroxyproline content increased in the viable left ventricular tissue in both
      the reperfused and non-reperfused groups. CONCLUSION: Reperfusion without
      myocardial salvage attenuates the increase in myocyte length and volume that
      occurs in remodeling myocardium following infarction in the rat, with no effect
      on the increase in collagen content. These data indicate that patency of the
      infarct vessel, which is known to have an inhibitory effect on infarct expansion,
      also has an anti-remodeling effect remote from the area perfused by this artery.

PMID- 9534856
TI  - Rigor tension in single skinned rat cardiac cell: role of myofibrillar creatine
      kinase.
AB  - OBJECTIVE: To elucidate the role of bound creatine kinase in adenine nucleotide
      compartmentation in myofibrils, the effects of this enzyme's substrates and
      products on rigor tension were studied in using isolated skinned rat
      cardiomyocytes rather than fibers, to avoid restrictions due to concentration
      gradients within the multicellular preparations. METHODS: A new experimental set
      up was built to allow continuous and stable measurements of force developed by
      cells. Triton X-100-treated cardiomyocytes were glued between a glass holder and
      the needle of a galvanometer. A feedback system allowed the precise measurement
      of force by recording the coil current necessary to prevent movement of the
      needle. RESULTS: At very low [Ca2+] (pCa 7), as MgATP level decreased, rigor
      tension appeared. In the absence of phosphocreatine (PCr), this tension started
      to rise at MgATP concentrations several times higher than in the presence of 12
      mM PCr. In the absence of PCr, the pMgATP/tension curves of single cells usually
      had a complicated relationship which could not be analyzed by a simple Hill
      equation. In the absence of PCr, 250 microM MgADP strongly potentiated rigor
      tension development in the 1 mM-3 microM range of [MgATP]; at 100 microM MgATP,
      in the presence of MgADP, the tension was 4.6 times higher than in the absence of
      MgADP. Addition of 12 mM PCr immediately eliminated rigor. Finally, in the
      presence of 100 microM MgATP and 250 microM MgADP, a decrease in PCr resulted in
      rigor; the half-maximal contracture being recorded at 1 mM PCr. CONCLUSIONS:
      These results indicate a myofibrillar compartmentation of adenine nucleotides
      influenced by bound creatine kinase, since at equal MgATP concentrations in
      extramyofibrillar milieu the response of myofibrils strongly depends on the
      presence of PCr. Local accumulation of ADP in myofibrils due to a fall in
      cellular PCr and inability of myofibrillar creatine kinase to rephosphorylate ADP
      produced by myosin ATPase could be an important mechanism of diastolic tension
      rise in ischaemic conditions.

PMID- 9534857
TI  - Downregulation of natriuretic peptide C-receptor protein in the hypertrophied
      ventricle of the aortovenocaval fistula rat.
AB  - OBJECTIVES: This study examined the expression of the C-type receptor for the
      natriuretic peptide family (NPR-C) in the ventricles of normal and aortovenocaval
      (AV)-fistula rats, the latter a model of cardiac volume overload producing
      hypertrophy of both ventricles. METHODS: Western blotting with a rabbit anti-NPR
      C antibody was used to quantify NPR-C levels in ventricular membranes. NPR-C
      expression was localised anatomically and measured in frozen sections of cardiac
      tissue by histochemistry and in vitro autoradiography. RESULTS: Western blot
      analysis revealed a single band (approximately 120 kDa) in ventricular membranes
      which was reduced to approximately 60 kDa after treatment with beta
      mercaptoethanol. NPR-C immunoreactivity and [125I]rat ANP1-28 binding
      (displaceable by the NPR-C-specific ligand C-ANP 4-23) were localised to the
      endocardium. NPR-C protein levels, as measured by all three techniques, were
      reduced significantly in the hypertrophied ventricles of AV-fistula rats compared
      to sham-operated animals. CONCLUSIONS: Volume-induced cardiac hypertrophy in the
      AV-fistula rat is associated with downregulation of endocardial NPR-C. This may
      be one mechanism by which the endocardium regulates the myocardial response to
      changes in haemodynamic load.

PMID- 9534858
TI  - Effects of positive pressure on both femoral venous and arterial blood velocities
      and the cutaneous microcirculation of the forefoot.
AB  - OBJECTIVE: The balance between the apparent beneficial effect and the risk of
      arterial ischaemia resulting from an external uniform compression is unclear. The
      purpose of this study was to determine the effects of a positive uniform
      compression on the lower limb circulation until a critical threshold was reached.
      METHODS: We used Doppler ultrasound to measure femoral venous and arterial blood
      velocities. The effects of positive pressure on cutaneous microcirculation were
      evaluated by laser Doppler flux (LDF), transcutaneous oxygen pressure (tcpO2) and
      transcutaneous carbon dioxide pressure (tcpCO2) on the forefoot of 17 healthy
      subjects. RESULTS: The results are expressed as median [lowest observed value
      highest observed value]. Whereas the arterial femoral velocity (A.F.V.) decreased
      from 0.21 [0.08-0.36] to 0.17 [0.08-0.28] m s-1 for an external pressure as low
      as 10 mmHg (p < 0.001), the venous femoral velocity (V.F.V.) decreased from 0.13
      [0.06-0.40] to 0.09 [0.05-0.34] m s-1 at 20 mmHg (p < 0.001). An increase of
      tcpCO2 from 39.8 [29.9-53.7] to 40.2 [30.0-55.5] mmHg (p < 0.05) and a decrease
      of LDF from 8.7 [3.1-25.9] to 5.5 [2.3-21.1] A.U. (p < 0.001) occurred at 10
      mmHg. However, tcpO2 decreased only from 76.7 [40.2-91.2] to 64.6 [18.9-85.2]
      mmHg when the splint pressure reached 60 mmHg (p < 0.05). The observed parameters
      (LDF, tcpO2, V.F.V. and A.F.V.) decreased further (except for tcpCO2 which
      increased) up to the end of the study as the applied pressure was increased.
      CONCLUSION: Positive pressure on the full leg provided no significant beneficial
      effect on femoral venous blood velocity. Whereas we showed that for an external
      uniform pressure as low as 10 mmHg, significant impairments in both arterial
      inflow of the lower limb and microcirculation of the forefoot appeared in
      recumbent healthy young subjects.

PMID- 9534859
TI  - The impact of ischemic heart disease on main pulmonary artery blood flow
      patterns: a comparison between magnetic resonance phase velocity mapping and
      transesophageal color Doppler.
AB  - OBJECTIVE: To give a detailed evaluation on main pulmonary artery blood velocity
      patterns, in patients with ischemic heart disease and to provide recommendations
      for pulsed Doppler sample volume placement, in order to optimize cardiac output
      estimation. METHODS: Using magnetic resonance phase and esophageal color Doppler
      velocity mapping in 12 patients with ischemic heart disease and undergoing
      coronary artery by-pass grafting, very similar data on pulmonary artery blood
      velocity patterns were provided for comparison with each other. RESULTS: Peak
      blood velocities were located in the inferior half of the main pulmonary artery
      cross-sectional area. Early after peak systole the highest velocities shifted
      towards the superior/left (major curvature) with a simultaneous decrease in
      velocities inferiorly. The velocity decrease further evolved into retrograde flow
      to the inferior/right (minor curvature). This feature was significantly enhanced
      compared to earlier findings in healthy volunteers. The mean temporal blood
      velocity profiles were asymmetrically skewed, thereby giving unreliable cardiac
      output estimates based on single point Doppler blood velocity recordings. The
      error incurred may amount to more than 100% in extreme cases. According to our
      data, optimal assessment of cardiac output should be based on multiple sample
      volumes placed along the inferior/right to superior/left diameter. CONCLUSIONS:
      MR-phase velocity mapping and multiplane transesophageal color Doppler recordings
      provided similar blood velocity patterns in patients with ischemic heart disease.
      The skewness of the mean temporal blood velocity profile is enhanced compared
      with healthy subjects, resulting in error in the assessment of CO by means of
      pulsed Doppler echocardiography. By using multiple Doppler sample volumes, the
      error can be minimized.

PMID- 9534860
TI  - ACE-inhibition prevents postischemic coronary leukocyte adhesion and leukocyte
      dependent reperfusion injury.
AB  - OBJECTIVE: Polymorphonuclear leukocytes (PMN), retained in the microvascular bed,
      can contribute to postischemic myocardial reperfusion injury. Since a beneficial
      effect of ACE-inhibition on reperfusion injury has been reported, we investigated
      the impact of cilazaprilat on PMN dependent reperfusion injury in isolated guinea
      pig hearts. METHODS: Hearts (n = 5 per group) were subjected to 15 min of
      ischemia. Immediately thereafter, a bolus of PMN was injected into the coronary
      system. External heart work (EHW) and total cardiac nitric oxide release were
      measured. For microscopic evaluation, hearts received rhodamine 6G labelled PMN
      after ischemia, were arrested 5 min later and further perfused with FITC dextran
      (0.1%). Localization of retained PMN was assessed by fluorescence microscopy.
      Leukocyte activation was studied by FACS analysis of the adhesion molecule CD11b
      before and after coronary passage of the PMN. The ACE-inhibitor cilazaprilat
      (Cila, 2 microM) and the NO-synthase inhibitor nitro-L-arginine (NOLAG, 10
      microM) were used to modulate nitric oxide formation of the heart. RESULTS:
      Postischemic EHW recovered to 67 +/- 5% (controls) and 64 +/- 6% (Cila) of the
      preischemic value. Addition of PMN severely depressed recovery of EHW (39 +/- 2%)
      and NO release (39 +/- 6% of the preischemic value). Simultaneously, ischemia led
      to a substantial increase in postcapillary PMN adhesion (from 21 +/- 5 to 172 +/-
      27 PMN/mm2 surface) and CD11b-expression of the recovered PMN (3-fold). Cila
      attenuated postischemic PMN adhesion (83 +/- 52 PMN/mm2) and activation of PMN,
      whereas it improved recovery of work performance (64 +/- 4%) and NO release (65
      +/- 4%) in the presence of PMN. Conversely, NOLAG increased PMN adhesion (284 +/-
      40 PMN/mm2) and myocardial injury. We conclude that ACE-inhibition prevents
      leukocyte dependent reperfusion injury mainly by inhibition of postcapillary
      leukocyte adhesion. The effect may be mediated by NO, given the proadhesive
      effect of NOLAG.

PMID- 9534861
TI  - Predictors of luminal narrowing by neointima after angioplasty in atherosclerotic
      rabbits.
AB  - OBJECTIVE: The present study was designed to identify the predictors of cross
      sectional area narrowing by neointima (%CSAN-N) after balloon angioplasty (BA) in
      the cholesterol fed rabbit model. METHODS: Angiographic, histomorphometric, and
      immunohistochemical data were analyzed from 91 femoral arteries of New Zealand
      white rabbits. Focal atherosclerosis was induced by air desiccation of the
      endothelium followed by a 2% cholesterol diet for 28 days. The rabbits received
      heparin (150 U/kg) at the time of BA (2.5 mm; three, 60-second, 10-atm
      inflations). Arteries were perfusion-fixed and excised 7 (n = 16), 14 (n = 11),
      21 (n = 9), or 28 (n = 20) days after BA. Non-angioplastied arteries were de
      endothelialized (cholesterol-fed [n = 12] or normal diet [n = 8]), non-injured
      but cholesterol-fed (n = 7), or normal (n = 8). RESULTS: Univariate regression
      across all groups showed that the absolute area of the lumen by histomorphometry
      (LA) correlated significantly with the area bounded by the external elastic
      lamina (EEL) (vessel size), but no correlation was found with the absolute area
      of neointima or media, the percentage disruption of the internal elastic lamina
      (IEL), or the percentage of neointima and media occupied by foam cells. However,
      %CSAN-N correlated significantly with the area bounded by the EEL, significantly
      with the absolute neointimal area, and negatively with the absolute LA (p <
      0.0001). Significant correlations were also found between %CSAN-N and the % IEL
      disrupted, the area of neointima and media occupied by RAM-11 + foam cells, and
      the loss of alpha-actin positivity in the media (p < 0.0001). CONCLUSIONS: These
      studies show that neointimal formation contributes significantly to luminal
      narrowing 1 month after angioplasty in this model, that the degree of vascular
      injury and the extent of foam cell accumulation in the neointima and media are
      significant independent predictors of neointimal formation, and that the area of
      the neointima, and the percent narrowing by neointima, are important predictors
      of remodeling itself (EEL area). These predictors were not identifiable when the
      analysis was focused on the determinants of absolute luminal area alone.

PMID- 9534862
TI  - Selective alpha v beta 3 integrin blockade potently limits neointimal hyperplasia
      and lumen stenosis following deep coronary arterial stent injury: evidence for
      the functional importance of integrin alpha v beta 3 and osteopontin expression
      during neointima formation.
AB  - Lumen loss from vascular restenosis remains a leading cause of chronic
      revascularization failure. OBJECTIVE: We hypothesized that cell-matrix adhesion,
      migration, and differentiation events that underlie restenosis are mediated by
      alpha v beta 3 integrin-ligand interactions. METHODS: Using immunohistochemistry
      and in situ hybridization, we examined the spatial and temporal vessel wall
      expression of alpha v beta 3 and osteopontin following deep coronary arterial
      injury. Cell migration and adhesion assays were performed to demonstrate the
      affinity and specificity of XJ 735 for various vessel wall integrins. The effects
      of XJ 735 (a selective cyclic Arg-Gly-Asp (RGD) peptidomimetic alpha v beta 3
      antagonist) on neointimal hyperplasia and lumen stenosis were tested in a porcine
      coronary injury model. Normolipemic swine underwent oversized stent injury
      followed by XJ 735 administration (9 animals, 28 lesions; 1 mg/kg bolus + 7 days
      4 mg/kg/d infusion + 21 days 2 mg/kg i.v. bolus 12 hourly) or placebo (10
      animals, 30 arterial lesions). RESULTS: Maximal alpha v beta 3 immunoreactivity
      was observed between 7-14 days following injury in the neointima, media, and
      adventitia. Maximal osteopontin mRNA signal in the neointima, media, and
      adventitia was observed at 14, 7 and 28 days respectively. IC50 for XJ 735 alpha
      v beta 3-mediated inhibition of human and porcine endothelial cell adhesion, and
      vascular smooth muscle cell migration, ranged from 0.6 to 4.4 microM. In
      contrast, IC50 for porcine or human alpha IIb/beta 3, alpha 4 beta 1, alpha v
      beta 5, and alpha 5 beta 1 inhibition exceeded 100 microM. Steady state XJ 735
      plasma levels exceeded 5 microM. Despite slightly higher injury scores in XJ 735
      treated animals, significant reductions in mean neointima area (43% reduction; p
      = 0.0009), and mean percent lumen stenosis (approximately 2.9 fold reduction; p =
      0.04) were observed in XJ 735 treated animals. XJ 735 treatment did not
      significantly alter the relative size of the arterial injury and reference sites
      (geometric remodeling). Comparison of neontima area vs. injury score regression
      lines revealed significant reductions in slope (p = 0.0001) and intercept (p =
      0.0001) for XJ 735. CONCLUSIONS: Selective alpha v beta 3 blockade is an
      effective anti-restenosis strategy that potently limits neointimal growth and
      lumen stenosis following deep arterial injury. The co-ordinate spatial and
      temporal upregulation of alpha v beta 3 expression following vessel wall injury,
      and the high affinity and specificity of XJ 735 for alpha v beta 3, confirms the
      importance of this integrin in adhesive and migratory cell-matrix events
      underlying coronary restenosis.

PMID- 9534863
TI  - L-arginine inhibits smooth muscle cell proliferation of vein graft intimal
      thickness in hypercholesterolemic rabbits.
AB  - OBJECTIVE: The effect of the chronic administration of L-arginine on intimal
      thickness and the kinetics of smooth muscle cell proliferation in autovein grafts
      in hypercholesterolemic rabbits were examined. METHODS: Male rabbits were fed a
      1% cholesterol diet (control group) and a 1% cholesterol diet supplemented by
      2.25% L-arginine HCl in drinking water (arginine group). Each group underwent
      reversed autologous vein bypass grafting of the left common carotid artery using
      the left external jugular vein. At 2 or 4 weeks after operation, intimal cell
      proliferation was determined by 5-bromo-2'-deoxyuridine (BrdU) incorporation and
      intimal thickness of the graft was measured with an ocular cytometer. At 4 weeks
      after operation, endothelium-dependent responses were examined by isometric
      tension recording. RESULTS: At 4 weeks after operation, the level of plasma
      arginine and citrulline are significantly higher in the arginine group (n = 7),
      compared with the control (n = 7). Intimal thickness in the arginine group (n =
      7) was significantly reduced, compared with that of the control (n = 7). At 2
      weeks after operation, the BrdU labeling index of the control (n = 5) was
      significantly higher than that of the arginine group (n = 5). At 4 weeks after
      operation, ACh caused endothelium-dependent relaxation in the arginine group (n =
      4), while in the control (n = 4), ACh did not relax. CONCLUSIONS: These results
      suggest that smooth muscle cell proliferation of the rabbit jugular vein grafts
      during hypercholesterolemia occurs at an early stage after graft implantation,
      prior to the development of intimal thickness. Intimal thickness of vein graft
      during hypercholesterolemia was reduced by chronic administration of dietary L
      arginine, by inhibiting smooth muscle cell proliferation. The enhancement of NO
      production in the blood vessel wall may therefore be useful for preventing late
      graft failure.

PMID- 9534864
TI  - Indomethacin enhances endothelial NO release--evidence for a role of PGI2 in the
      autocrine control of calcium-dependent autacoid production.
AB  - OBJECTIVE: We studied whether NO or prostacyclin (PGI2), which are continuously
      released by endothelial cells, have autocrine/paracrine effects on the calcium
      dependent autacoid production by modulating the intracellular Ca2+ concentration
      ([Ca2+]i). METHODS: Histamine(His)-induced [Ca2+]i increases (Fura 2-method) and
      NO-dependent cGMP increase were measured in human umbilical vein endothelial cell
      (HUVECs) before and after cyclooxygenase inhibition or application of cAMP- and
      cGMP-elevating drugs. RESULTS: 0.3 microM His increased endothelial [Ca2+]i from
      77 +/- 2 nM to 418 +/- 59 nM. The His-induced [Ca2+]i increases were
      significantly attenuated following treatment with PGI2 (by 23%) and forskolin (by
      33%), both increasing the cAMP release from HUVECs (by 49% and 66%). The His
      induced [Ca2+]i increases were inhibited by the protein kinase A-activator cBIMPS
      (by 61%) which also abolished the His-induced PGI2 release. Conversely,
      inhibition of the PGI2 production with indomethacin significantly augmented the
      His-induced [Ca2+]i increases (by 32%), resulting in a significantly augmented NO
      production as indicated by an enhanced LNNA-sensitive cGMP increase in HUVECs. In
      contrast, neither increases of cGMP (basal 0.4 +/- 0.1 pmol/mg) elicited by 10
      microM SNP (21 +/- 2 pmol/mg) or 10 microM C-type natriuretic peptide (CNP, 4.6
      +/- 1.6 pmol/mg) nor its reduction by 30 microM LNNA had any effect on the His
      induced [Ca2+]i increases. CONCLUSION: PGI2 attenuates agonist-induced [Ca2+]i
      increases by a cAMP-dependent mechanism, thereby modulating not only its own
      synthesis via a negative feedback but also that of NO. Consequently, reduced PGI2
      levels result in an increased NO production. NO which does not cause a negative
      feedback control by cGMP might therefore compensate for the lack of PGI2.

PMID- 9534866
TI  - Reduced myocardial cyclic GMP increases myocardial O2 consumption in control but
      not renal hypertension-induced cardiac hypertrophy.
AB  - OBJECTIVES: We tested the hypothesis that a reduction in myocardial cyclic GMP
      would increase myocardial O2 consumption and that renal hypertension (One Kidney
      One Clip, 1K1C)-induced cardiac hypertrophy would change this relationship.
      METHODS: Either vehicle or LY83583 (10(-3) M, a guanylate cyclase inhibitor) was
      topically applied to the left ventricular surface of control of 1K1C anesthetized
      open-chest New Zealand white rabbits (N = 38). Coronary blood flow (radioactive
      microspheres) and O2 extraction (microspectrophotometry) were used to determine
      subepicardial (EPI) and subendocardial (ENDO) O2 consumption and myocardial
      cyclic GMP was determined by radioimmunoassay. RESULTS: The heart weight/body
      weight ratio was greater in the 1K1C rabbits (3.16 +/- 0.20) than controls (2.58
      +/- 0.08 g/kg). Systolic blood pressure was higher in 1K1C rabbits (116 +/- 8 mm
      Hg) than controls (80 +/- 6), but topical LY83583 had no significant hemodynamic
      effects. LY83583 significantly and similarly decreased EPI cyclic GMP in both
      control (7.9 +/- 1.2 to 6.0 +/- 1.0 pmol/g) and 1K1C (7.7 +/- 1.2 to 5.3 +/- 0.9)
      hearts and control ENDO (8.7 +/- 1.7 to 7.2 +/- 1.2) but not 1K1C ENDO (6.7 +/-
      0.5 to 5.7 +/- 1.1). Myocardial O2 consumption was significantly increased in
      control with LY83583 (EPI 6.6 +/- 1.1 to 15.6 +/- 1.4 and ENDO 7.2 +/- 0.9 to
      14.2 +/- 0.7 ml O2/min/100 g), but not in 1K1C hearts (EPI 12.1 +/- 1.0 to 12.9
      +/- 1.2 or ENDO 11.4 +/- 0.7 to 12.9 +/- 0.9). CONCLUSIONS: Thus myocardial O2
      consumption was only increased by LY83583 in control hearts, but LY83583
      decreased cyclic GMP similarly in both the control and 1K1C EPI. This indicated,
      at least in the EPI, a dissociation of the inverse relationship between the
      myocardial level of cyclic GMP and O2 consumption in the 1K1C rabbit heart.

PMID- 9534865
TI  - NO activity in familial combined hyperlipidemia: potential role of cholesterol
      remnants.
AB  - OBJECTIVE: Patients with familial combined hyperlipidemia (FCH) have an increased
      cardiovascular mortality despite only moderate elevations of LDL-cholesterol.
      Since endothelial NO release is intimately involved in the anti-atherosclerotic
      effects of the endothelium, we studied the effect of short-term lipid-lowering
      therapy on NO-mediated vasodilatation in patients with FCH. In view of only
      moderate LDL elevations, we evaluated whether alterations in other lipid
      fractions upon therapy correlated to changes in NO-mediated vasodilatation.
      METHODS: NO activity was assessed by serotonin-induced, nitric oxide-mediated
      increase in forearm blood flow (FBF). Measurements were performed 2 weeks off and
      4 weeks on lipid-lowering therapy in 12 FCH patients using forearm venous
      occlusion plethysmography. Control experiments were performed in 12 healthy
      subjects. RESULTS: Serotonin-induced vasodilatation was impaired in FCH patients
      (FBF (unit ml/100 ml forearm tissue/min) from 3.0 (0.3) to 4.8 (0.4)) compared to
      controls (FBF from 2.9 (0.3) to 6.5 (0.6); p < 0.05 vs. FCH). FBF response to
      serotonin improved significantly upon lipid-lowering therapy (from 3.0 (0.3) to
      5.7 (0.5); p < 0.05 treated vs. untreated). The level of improvement in
      endothelial function was significantly correlated to the absolute reduction of
      intermediate density lipoproteins upon lipid-lowering therapy (r = -0.64; p <
      0.05), whereas it did not correlate to changes in VLDL- or LDL-cholesterol, nor
      to Lp(a). CONCLUSION: Patients with familial combined hyperlipidemia have
      impaired NO-mediated vasodilatation, that responds rapidly to lipid lowering
      medication, and may be related to changes in intermediate density lipoproteins.

PMID- 9534867
TI  - The EC novel foods Regulation--a UK perspective.
AB  - On 15 May 1997 the EC novel foods Regulation came into effect introducing a
      statutory pre-market approval system for novel foods across the whole of the
      European Union. A novel food is defined as a food which has not been consumed to
      a significant degree and includes foods containing or obtained from genetically
      modified organisms. The Regulation envisages an initial safety assessment at
      Member State level, although centralized procedures are available to resolve any
      objections between Member States. The most controversial aspect of the Regulation
      relates to the provisions for labelling genetically modified foods. Within the
      framework of the Regulation there is scope for labelling to be considered on a
      case by case basis, although the UK is pressing for all foods which may contain
      genetically modified material to be clearly labelled. To ensure that all Member
      States follow a consistent approach to the safety assessment of novel foods, the
      Commission has published a series of guidelines to accompany the regulation. The
      UK already has a well-developed system for assessing the safety of novel foods
      dating back to the approval of the first novel food in the UK in 1983.

PMID- 9534868
TI  - A survey of vitamin A concentrations in the liver of food-producing animals.
AB  - High oral doses of vitamin A have been shown to be teratogenic and accordingly
      the World Health Organization has recommended that the daily intake for pregnant
      women should not exceed 3.3 mg. Liver contains high concentrations of this
      vitamin and consequently it has become necessary to assess its level in the
      livers of food animals. A survey of fresh, frozen, imported and home-produced
      retail liver samples from calf (42), ox (121), lamb (228), pig (133) and chicken
      (125) was carried out between August 1992 and April 1993 using a modified version
      of the method of Ashoor and Knox (1987) to determine retinol and retinyl esters.
      Interlaboratory comparison showed no significant difference in results for this
      method and a method which employed hydrolysis of retinyl esters, and there were
      significant advantages in specificity, simplicity, cost and quality control. The
      mean +/- sd total vitamin A concentration calculated as retinol equivalents, for
      all species surveyed was 139 +/- 96 with a range of 3-1267 mg/kg liver. Mean
      values for individual species were: calf 188 +/- 125, ox 142 +/- 110, lamb 173 +/
      104, pig 174 +/- 118 and chicken 97 +/- 44 mg/kg liver. No change in the vitamin
      A concentrations in liver were observed compared with previous surveys in the UK,
      which suggests that the intake of vitamin A from dietary and supplementary
      sources by different species has not changed. The data from this survey confirm
      that liver cannot be recommended as a food for pregnant women.

PMID- 9534869
TI  - Residues of polychlorinated biphenyls (PCB) in fatty foods of the Canadian diet.
AB  - Market basket samples representative of food from six Canadian cities were
      surveyed from 1992 to 1996. Fifty composites of fatty foods, prepared for
      consumption were analysed for 40 PCB congeners by gas chromatography-mass
      spectrometry. Fish and butter contained the highest total PCB concentrations,
      while milk and infant foods contained the lowest. The dairy and meat composites
      were major contributors to the total PCB intake of 5.7 ng/kg/day, and to the TEQ
      (2,3,7,8-tetrachloro-p-dibenzodioxin equivalent) intake of 0.11 pg/kg/day. The
      pattern of congeners was similar for the different food groups with the exception
      of fish, which contained less tri- and tetra-chlorinated biphenyls and more of
      the hexachlorinated congener No. 153.

PMID- 9534870
TI  - Mycotoxins in ingredients of animal feeding stuffs: II. Determination of
      mycotoxins in maize and maize products.
AB  - Analytical methods have been developed for the reliable detection and estimation
      of 22 mycotoxins in maize gluten and other maize products used in the animal feed
      industry. The mycotoxins are aflatoxins B1, B2, G1 and G2, ochratoxins A and B,
      citrinin, cyclopiazonic acid, zearalenone, sterigmatocystin, deoxynivalenol,
      nivalenol together with seven related trichothecene mycotoxins, fumonisins B1 and
      B2 and moniliformin. For most of the mycotoxins, recoveries obtained were 60% or
      greater and reproducibility data were better than +/- 40%. In general, the
      analysis of maize gluten proved more difficult than for other maize products. In
      total 40 samples of maize gluten, and 27 samples of other maize products were
      examined. Aflatoxins were not found above the reporting limit (1-5 micrograms/kg)
      in any sample while ochratoxin A was detected in only two samples of maize gluten
      at 2 micrograms/kg. No sterigmatocystin or cyclopiazonic acid were detected
      although the limits of detection for these toxins were poor. Twenty percent of
      maize gluten samples contained zearalenone at up to 500 micrograms/kg while all
      other maize products also contained this mycotoxin. Highest levels occurred in
      screenings and meal while the lowest amounts were in flaked maize and germ. Many
      samples contained a multi-toxin mixture of trichothecenes, fumonisins and
      moniliformin. The most highly contaminated samples of maize screenings and maize
      meal contained a mixture of zearalenone, deoxynivalenol, nivalenol, fumonisin B1
      and B2, moniliformin, each in mg/kg amounts and lower amounts of other
      trichothecenes such as 15-acetoxy deoxynivalenol, HT-2 toxin and T-2 toxin.
      Fumonisins occurred in all except two gluten samples and occurred up to a level
      of 32 mg/kg in maize screenings, 13 mg/kg in maize meal and 8 mg/kg in maize
      germ.

PMID- 9534871
TI  - Production of alternariol and alternariol mono-methyl ether by isolates of
      Alternaria spp. from Argentinian maize.
AB  - Alternaria cultures (87 isolates of Alternaria alternata, four of A. tenuissima,
      two of A. radicina, and three of Alternaria state of Pleospora infectoria
      respectively, from maize) were screened to determine their ability to produce
      alternariol (AOH) and alternariol monomethyl ether (AME) on maize and rice. Only
      28 A. alternata stains had toxigenic capacity. When maize was used as substrate
      21 of 28 isolates produced AOH and AME, and 23 of 28 strains produced AOH and 22
      of 28 produced AME when rice was used. The level of AOH produced by the isolates
      ranged from 0.3 to 2.1 mg/kg on maize and from 0.4 to 9.9 mg/kg on rice. The AME
      production by the stains ranged between 0.3 and 3.3 mg/kg both on maize and on
      rice. These results could indicate a low probability of AOH and AME occurring
      naturally on maize in Argentina.

PMID- 9534872
TI  - The distribution of nine pesticides between the juice and pulp of carrots and
      tomatoes after home processing.
AB  - The distribution of nine pesticides between the juice and pulp of carrots and
      tomatoes during home culinary practices was investigated. Tomato and carrot pulp
      contained a higher percentage of all pesticide residues, except for mancozeb in
      tomatoes. Although there was a difference in the relative distribution of the
      pesticides between the commodities with greater amounts present in the pulp of
      tomatoes, the pesticides followed a similar trend in both. A relationship between
      the pulp/juice distribution and water solubility of the pesticide was apparent.
      Pesticides with the highest water solubility were present to a greater extent in
      the juice. An exception was noted in the case of diazinon and parathion, which
      were present in higher amounts in the pulp than their water solubility would
      suggest. The percent residue in the pulp ranged from 56.4 to 75.2% for carrots,
      and 49.7 to 95.4% for tomatoes. Residues in the juice prepared from washed
      commodities ranged from not detected to 0.83 microgram/g. Washing of the produce
      removed more residue from carrots than from tomatoes, but it did not affect the
      relative distribution of the residues. The behaviour and fate of the chemical
      varied with the pesticide as well as the crop.

PMID- 9534873
TI  - Specific migration testing with alternative fatty food simulants.
AB  - Many additives used in plastics materials and articles intended for food contact
      are expected to be assigned specific migration limits (SMLs) in a future
      amendment to EC Directive 90/128/EEC. In order to demonstrate compliance with
      these restrictions, specific migration tests will need to be performed on the
      finished plastics packaging using foods or the appropriate EC food simulants.
      Owing to the involatile and lipophilic nature of many of these additives, their
      analysis in the conventional fatty food simulant, olive oil, presents technical
      difficulties. One way of overcoming these difficulties would be to use a simple
      solvent alternative to olive oil as has been proposed for overall migration
      testing. The objective of this work is to compare specific migration data
      obtained using olive oil with alternative fat simulants iso-octane and 95%
      ethanol, to find out if similar results are obtained and identify the most
      appropriate alternative simulant to use for future testing. Good agreement with
      the olive oil migration data was obtained using 95% ethanol (equivalent exposure
      conditions) for both of the additives studied in polyolefins. For the polystyrene
      materials studied it is unlikely that the SMLs for the two additives would be
      exceeded, and in these cases iso-octane (1.5 h at 60 degrees C) could be used as
      a rapid 'alternative test'.

PMID- 9534874
TI  - Combined GC and sniffing port analysis of volatile compounds in rubber rings
      mounted on beer bottles.
AB  - For product development reasons two types (A and B) of rubber rings, used on
      clasps of swing top beer bottles, were investigated for the presence of volatile
      compounds, which could affect the taste/odour of the packed beer due to (vapour
      phase) migration. Samples were incubated under different conditions and, after
      dynamic headspace sampling, analysed by combined GC and sniffing port analysis.
      Compounds were also identified by GC-MS. The main differences were located in the
      presence of isobutene isomers in Ring Type A, which were absent in Ring Type B.
      These compounds were described mainly as 'toy-like' and 'rubber'. Therefore the
      risk for off-flavour development is expected to be diminished by using Ring Type
      B.

PMID- 9534875
TI  - Design of a test for migration studies in the vapour phase.
AB  - A new test for migration studies in the vapour phase has been developed. The
      system consists of placing the packaging material containing the potential
      migrants in a glass vial together with the solid adsorbent, Tenax GC. The vial is
      introduced into an oven at a controlled temperature for different periods of
      time. Once the migration test has finished, Tenax is extracted by supercritical
      fluid chromatography (SFE) and analysed by GC-ECD. Migration conditions of 7 days
      at 80 degrees C are proposed. The results obtained are discussed.

PMID- 9534876
TI  - A systematic study on the stability of selected polymer antioxidants in EU
      official aqueous and alternative food simulants using HPLC.
AB  - Whilst considerable research has been conducted on the stability of plastics
      additives during processing, there is, on the other hand, a lack of studies on
      the stability of the same additives in food simulants in the published
      literature. In the work presented a systematic study has been undertaken on the
      stability of five selected commercial plastics additives (Irganox 3114, Irganox
      1035, Irganox 245, Irganox 1098 and Irgafos P-EPQ) in the three EU-official
      aqueous food simulants (distilled water, 3% aq. acetic acid and 15% aq. ethanol)
      and in an alternative fat simulant (95% aq. ethanol) under two different
      time/temperature exposure conditions (10 days at 40 degrees C and 1 h at 100
      degrees C). To enable quantitative analysis of the additives for this
      investigation, a simple and rapid HPLC method with UV detection was developed.
      The results obtained showed that the four Irganox-type additives under
      investigation were practically stable under the applied exposure conditions in
      all of the employed food simulants. Only Irganox 3114 exhibited a relatively low
      degree of instability in the ethanolic food simulants. Concerning Irgafos P-EPQ,
      a mixture of at least seven constituents, a remarkable degradation in ethanol and
      acetic acid solutions was observed. The developed HPLC method is also considered
      to be applicable for stability testing of other Irganox-type additives both in
      aqueous and fatty food simulants.

PMID- 9534877
TI  - Alternative test methods to control the compliance of polyolefin food packaging
      materials with the European Union regulation: the case of aromatic antioxidants
      and of bis(ethanolamine) antistatics based on 1H-NMR and UV-visible
      spectrophotometry.
AB  - In order to decide whether a plastic food packaging material complies with the
      European Communities (EC) regulation on migration, a quick analysis of two
      functional classes of plastics additives (aromatic antioxidants and antistatic
      agents) from polyolefin materials by 1H-NMR and UV-visible spectrophotometry is
      presented. The scope of spectroscopic methods for alternative and migration tests
      is presented. 1H-NMR can be used in several ways, from a simple fingerprint of
      the potential migrants to an identification procedure. Extraction is optimized
      using UV spectrophotometry. Optimization relies on extraction kinetics, which
      include the demonstration that extraction is more severe than migration. Only a
      few hours are required to conclude whether a material complies with the
      regulation. The specific migration limits are expressed as specific absorbance
      limit values, alpha. These data can be annexed by food industries to
      specifications of a plastic packaging material.

PMID- 9534878
TI  - Sensory and chemical quality of UHT-milk stored in paperboard cartons with
      different oxygen and light barriers.
AB  - The sensory and chemical shelf-life of UHT-milk stored at room temperature and at
      6 degrees C in aluminium-foil, non-foil barrier (X-board) and PE cartons were
      investigated. UHT milk in aluminium-foil stored in the dark has a minimum shelf
      life of 6 months, while the shelf-life is 4-5 months in X-board and PE cartons.
      When PE cartons and X-board cartons are stored with strong light exposure at 6
      degrees C, a development of light-induced off-flavour is detected after 2 and 8
      weeks, respectively. The light-induced off-flavour effect is more pronounced than
      the effect of non-light induced oxidation of unsaturated lipids.

PMID- 9534879
TI  - Occurrence and significance of ochratoxin A in food.

PMID- 9534880
TI  - Hepatic cytochrome P450 CYP2C activity in psoriasis: studies using proguanil as a
      probe compound.
AB  - Retinol and proguanil are metabolised by the same family of hepatic cytochrome
      P450, i.e. CYP2C. We used proguanil as a probe to study CYP2C activity, and by
      implication retinol metabolism, in psoriasis. In vitro studies showed that
      retinol competitively inhibited the hepatic metabolism of proguanil to
      cycloguanil. Proguanil metabolism was assessed in 82 patients with chronic plaque
      psoriasis. Following proguanil orally (200 mg), urine was analysed for proguanil
      and cycloguanil. A proguanil to cycloguanil ratio < 1 signified extensive
      metabolism and a ratio > 10 poor metabolism. A wider range of ratios was observed
      in psoriasis than previously reported for normal subjects. The proguanil to
      cycloguanil ratio was assessed in 10 cases each of know severe and mild
      psoriasis. Low CYP2C activity was associated with severe psoriasis, poor
      metaboliser status occurring in 50% of the severe group, but in none of the mild
      cases, p < 0.01. These findings may indicate differences in retinoid metabolism
      in psoriasis.

PMID- 9534881
TI  - Psoriatic keratinocytes express high levels of nerve growth factor.
AB  - Many investigators have reported proliferation of terminal cutaneous nerves and
      upregulation of various neuropeptides (substance P, vasoactive intestinal
      polypeptide, calcitonin gene-related peptide) in psoriatic lesions. Nerve growth
      factor promotes growth of nerves and causes upregulation of neuropeptides like
      substance P and calcitonin gene-related peptide. In this study we investigated
      the expression of nerve growth factor in psoriatic lesions, non-lesional
      psoriatic skin, lichen planus and normal control skin. Immunoperoxidase staining
      was applied on cryosections prepared from snap-frozen biopsy specimens. The
      primary antibody used was a polyclonal anti-NGF-beta antibody. Nerve growth
      factor was detected only in the keratinocytes. In psoriatic tissue the number of
      keratinocytes per square millimeter of epidermis positive for nerve growth factor
      was 84.7 +/- 46.3 compared to 44.8 +/- 29.9, 18.9 +/- 11.8 and 7.5 +/- 16.9,
      respectively, in non-lesional psoriatic skin, normal skin and lichen planus.
      Increased expression of nerve growth factor substantiates larger numbers of
      terminal cutaneous nerves and upregulations of substance P and calcitonin gene
      related peptide in psoriatic lesions. In addition, nerve growth factor is
      mitogenic to keratinocytes, activates T-lymphocytes and can induce migration of
      inflammatory cellular infiltrates, histological features characteristic of
      psoriasis.

PMID- 9534882
TI  - Differential expression of nerve growth factor in Leishmania major murine
      cutaneous leishmaniasis.
AB  - The cross-talk between the immune and nervous systems is becoming an interesting
      field of research and there is accumulating evidence supporting this notion. In
      the present study we investigated the levels of nerve growth factor in a murine
      model of cutaneous leishmaniasis, using a two-site ELISA. Two strains of inbred
      mice were used for this purpose, namely BALB/c and C57BL/6, genetically
      susceptible and resistant, respectively, to infection with Leishmania major. This
      work demonstrates a difference in expression of nerve growth factor in the skin
      and secondary lymphoid organ microenvironment, as well as in the serum, between
      these mouse strains. The high nerve growth factor levels in the microenvironment
      seem to be important and possibly critical for the outcome of the disease.
      Compared with controls, the resistant strain, C57BL/6, expressed significantly
      increased nerve growth factor levels in the skin, secondary lymphoid organs and
      serum at 1 week post-infection, whereas the susceptible strain, BALB/c, showed no
      change in the skin and a slight increase in the lymphoid organs and serum at this
      time-point. These high nerve growth factor levels in the early stage of the
      disease, whether produced directly by the inflammatory cells or indirectly
      through its induction by other cytokines or both, might indicate a contribution
      of this neurotrophic factor to differentiation of naive T lymphocytes into either
      Th1 or Th2 subsets that fundamentally govern the disease outcome. The expression
      of significantly elevated nerve growth factor levels in the skin and lymphoid
      organs of C57BL/6 at the late studied time points might suggest a role for nerve
      growth factor in the resolution of the disease process, which is usually evident
      from 6 weeks post-infection in this model. The high nerve growth factor levels
      expressed in the skin, lymph nodes and serum of BALB/c at late stages of the
      disease may be explained as an attempt to counteract the progression and
      dissemination of the disease. This investigation adds further experimental
      evidence for an anti-inflammatory effect of nerve growth factor, possibly through
      its action as a link between the nervous and immune systems.

PMID- 9534883
TI  - Modulation of cutaneous SP receptors in atopic dermatitis after UVA irradiation.
AB  - Atopic dermatitis is a pruritic inflammatory skin disorder, involving
      immunological and non-immunological factors. Substance P seems to be involved in
      the pathogenesis of atopic dermatitis. Substance P-containing nerve fibers are
      increased in the lesional skin of patients with atopic dermatitis and a reduced
      weal and flare reaction to intradermal injection of substance P has been
      observed. We investigated the distribution of substance P receptors in the
      involved skin of patients before and after single or repetitive UVA irradiations.
      Our results indicate that substance P receptors of the NK-1 subtype are expressed
      on blood vessels and on epidermal keratinocytes of involved skin of patients with
      atopic dermatitis. UVA irradiations did not modify the epidermal distribution of
      substance P receptors but decreased their expression intensity on blood vessels.
      UVA irradiations seem to decrease skin inflammation through the modulation of NK
      1 receptor expression on endothelial cells.

PMID- 9534884
TI  - Free radicals as potential mediators of metal allergy: effect of ascorbic acid on
      lymphocyte proliferation and IFN-gamma production in contact allergy to Ni2+ and
      Co2+.
AB  - A possible free radical mechanism in metal allergy was investigated in peripheral
      blood mononuclear cell (PBMC) cultures from 6 subjects, contact allergic to Ni2+
      and Co2+, and 6 control individuals. Ni2+ and Co(2+)-mediated free radical
      generation was studied with electron spin resonance spectroscopy. The immune
      response was characterized by cellular [methyl-3H]thymidine uptake and interferon
      gamma (IFN-gamma) production Ni2+ and Co2+ (10-50 microM) significantly increased
      lymphocyte proliferation and IFN-gamma production in PBMC cultures from contact
      allergic subjects in comparison with cultures from controls. Inhibition of Co(2+)
      mediated free radical generation by ascorbic acid did not influence cellular
      [methyl-3H]thymidine uptake and IFN production. Detectable amounts of free
      radicals were not obtained with Ni2+. We therefore conclude that it is unlikely
      that free radicals are involved in contact allergy to Ni2+ and Co2+.

PMID- 9534885
TI  - Possible involvement of interleukin-1 in the pathogenesis of dermatofibroma.
AB  - Dermatofibroma (DF) is histologically characterized by proliferation of
      fibroblasts in the dermis. Multiple DFs occasionally develop in patients with
      autoimmune disorders under immunosuppressive therapy; however, the pathogenesis
      of DF is still unclear. To elucidate immunological involvement in the mechanism
      of the fibrosis in DF, we studied the role of interleukin-1 (IL-1), which has a
      number of biological functions, including proliferation and collagen production
      of fibroblasts, on DF-derived fibroblasts. 3H-thymidine incorporation was used to
      examine the effects of Il-1 alpha and IL-1 beta in 4 cultured fibroblast strains
      derived from DF and 5 fibroblast strains from normal skin. Expression of mRNA of
      IL-1 was also analyzed by reverse transcriptase polymerase chain reaction (RT
      PCR). Basal 3H-TdR incorporation without stimulant of DF-derived fibroblasts
      showed a significantly greater growth activity than normal skin-derived
      fibroblasts (2, 632 +/- 525 vs. 762 +/- 144 dpm, p < 0.01). Both IL-1 alpha and
      IL-1 beta showed a stronger growth-stimulatory activity on DF-derived fibroblasts
      in a dose-dependent manner than normal fibroblasts, and the percent 3H-TdR uptake
      of DF was 1.4-fold (IL-1 alpha; 1,000 U/ml) and 1.3-fold (IL-1 beta; 1,000 U/ml)
      as compared with normal fibroblasts; however, the differences did not reach any
      significance. When increasing concentrations of IL-1 receptor antagonist (IL-1
      alpha) were added to culture medium stimulated with IL-1 alpha, the proliferative
      response of fibroblasts was significantly reduced. Expression of IL-1 beta and
      RNA was detected on both DF-derived and normal skin-derived fibroblasts, while
      that of IL-1 alpha mRNA was detected only on DF-derived fibroblasts. Our results
      suggest that IL-1 may be involved in the fibrotic process in DF at the
      transcriptional level and play a role in the fibroblast proliferation in an
      autocrine manner.

PMID- 9534886
TI  - In vivo study of skin mechanical properties in scleredema of Buschke.
AB  - A non-invasive, in vivo suction device was used to investigate the mechanical
      properties of the skin in a patient with scleredema of Buschke. Clinical scoring
      of skin induration and measurements of skin elasticity were performed over 9
      anatomic regions on admission and after 3 (on discharge), 17 and 28 months.
      Immediate distension, final distension and immediate retraction were
      significantly decreased, while the viscoelastic to elastic ratio was
      significantly increased in the patient as compared to the healthy controls.
      Delayed distension and biological elasticity were preserved. Low values of skin
      distensibility correlated with a severe skin induration (p < 0.001). The changes
      were more expressive with the 8 mm-diameter measuring probe than the 2 mm
      diameter probe. The method applied can be used for objective and quantitative
      assessment of skin involvement in scleredema of Buschke.

PMID- 9534887
TI  - Expression of skin-derived antileukoproteinase (SKALP) in reconstructed human
      epidermis and its value as a marker for skin irritation.
AB  - For the investigation of the skin irritancy potential of chemicals in an in vitro
      model, it is necessary to have sensitive end-points that predict the effects on
      native human skin. Our aim was to investigate whether the induction of the
      proteinase inhibitor SKALP in reconstructed epidermis can be used as a marker.
      The influence of culture conditions and the effect of topical application of
      sodium lauryl sulfate and oleic acid on SKALP expression were evaluated using
      immunohistochemistry and Northern blotting. SKALP expression was induced by
      serum, epidermal growth factor and fibroblasts. In the presence of retinoic acid
      and 1,25-dihydroxyvitamin D3 SKALP expression was inhibited, whereas
      supplementation with ascorbic acid and a-tocopherol had no effect. Tape-stripping
      of excised skin and topical treatment with sodium lauryl sulfate induced SKALP
      protein expression. Application of sodium lauryl sulfate and oleic acid on
      reconstructed epidermis also induced SKALP at the protein level but no
      significant effects could be demonstrated at mRNA levels. In conclusion, SKALP
      expression, which was increased upon application of sodium lauryl sulfate and
      oleic acid, can be used as an in vitro end-point for skin irritancy, irrespective
      of the modifying effects of culture conditions.

PMID- 9534888
TI  - Laser Doppler imaging of skin microcirculation.
AB  - Laser Doppler imaging (LDI), a new technique which allows measurement of skin
      blood perfusion at a distance from the skin surface, was assessed
      methodologically in healthy volunteers. Each skin LDI value was based on
      virtually real-time measurements obtained from a number of discrete measuring
      sites. In scans made along the circumference of the lower arm, valid figures for
      LDI (as distinct from no output at all) were obtained in 8/8 measurements at 0
      degrees inclination, and in 16/16 measurements at 7 degrees, 14 degrees, 22
      degrees, 30 degrees and 38 degrees, respectively. Beyond this inclination a
      numerical output was obtained in only 9/16 of measurements at an inclination of
      48 degrees, in 7/16 at 69 degrees, and in no more than 1/16 at 90 degrees. Values
      obtained at angles of inclination greater than 38 degrees fell within the
      relatively narrow range of values obtained at lesser angles of inclination. The
      findings are of interest since measuring sites of clinical importance may not be
      flat. Variability of measurement (coefficient of variation in per cent) was
      studied in the lower leg by performing LDI and conventional laser Doppler
      flowmetry (LDF) concomitantly. The coefficient of variation for measurements in
      one subject at rest was 13% for LDI vs. 19% for LDF, the corresponding
      interindividual coefficient of variation values being 25% vs. 28%. In response to
      heating, finger pulp perfusion increased by 55% as measured by LDI (p = 0.0051)
      and by 44% (p = 0.0756) as measured by LDF. In summary, the findings contribute
      to the validation of LDI for skin perfusion measurement.

PMID- 9534889
TI  - An amorphous hydrogel enhances epithelialisation of wounds.
AB  - Hydrogel dressings are gaining increased clinical acceptance as a wound
      management modality. The purpose of this study was to compare the effect of three
      amorphous hydrogels with occlusive, control treatment (Tegaderm) on healing of
      experimental wounds. Eight partial-thickness cutaneous wounds (2.5 cm x 2.5 cm x
      0.04 cm) were made, using an electrokeratome, and the four treatments were
      allocated by randomisation within a cephalad and a caudal region on each of six
      60-kg domestic pigs. In total, twelve wounds were each treated with 2.0 ml of
      each type of hydrogel--an experimental amorphous hydrogel ("Exgel"), IntraSite
      Gel and a poloxamer gel containing 3% hydrogen peroxide--and covered with
      Tegaderm, or treated with Tegaderm alone. At 66 h post-operatively, formalin
      fixed, paraffin-embedded sections of wounds were hematoxylin-eosin-stained and
      assessed morphometrically for epithelium coverage in a blinded fashion. The Exgel
      remained macroscopically intact on the wounds in contrast to the other hydrogels,
      which had dissolved completely after treatment. Exgel significantly (p < 0.05)
      increased epithelial coverage of the wounds, compared with the other treatments
      (by 20% more than Tegaderm-treated wounds). In vitro experiments indicated that
      the polymeric matrix of Exgel sequesters bioactive molecules present in wound
      fluid and that it may in vivo act as a protective reservoir that delivers
      bioactive molecules at a rate that promotes epithelial migration. Exgel may
      represent a new treatment principle to promote wound healing.

PMID- 9534890
TI  - Histamine and cutaneous nociception: histamine-induced responses in patients with
      atopic eczema, psoriasis and urticaria.
AB  - Having observed altered itch and flare reactions after histamine application in
      patients with atopic eczema, we tried to determine these reactions in patients
      with urticaria and psoriasis. We investigated 16 healthy non-atopic subjects, 16
      atopics in an eczema-free interval, 16 with acute atopic eczema, 16 with
      urticaria and 16 with psoriasis. Histamine was iontophoretically applied. The
      resulting sensations were rated on a visual analogue scale. Flare areas were
      measured 6 min after stimulation. Itch ratings of urticaria and psoriasis
      patients did not differ significantly from controls, whereas both atopic groups,
      regardless of acute or symptom-free state, reported significantly reduced
      intensity of itching. Flares were significantly diminished in all subjects with
      acute skin disease (psoriasis, urticaria and atopic eczema), regardless of
      diagnosis. However, flares were "normal" in symptom-free atopics and were not
      significantly different from controls. In conclusion, all "acute" patients showed
      a diminished axon-reflex function, possibly due to a downregulation of C-fiber
      responsiveness to histamine or an increased turnover rate of inflammatory
      mediators. Both atopic groups reported weaker itching, suggesting altered central
      nervous processing of itch.

PMID- 9534891
TI  - Multiple basal cell carcinoma. A clinical evaluation of risk factors.
AB  - Basal cell carcinoma (BCC) is the most common malignant skin tumour. There is
      evidence that the number of patients who develop more than one basal cell
      carcinoma (mBCC) is increasing. The aim of this study was to elucidate possible
      risk factors for developing mBCC. Among twelve risk factors considered, skin
      tumour among relatives was the strongest, with an odds ratio of 10.9 (p < 0.001).
      The second strongest risk factor was sunburn after the age of 60, odds ratio 4.4
      (p < 0.001). The results suggest that the presence of skin tumour in the family
      and sunburn after age 60 are independent factors associated with mBCC. To our
      knowledge this has not previously been reported.

PMID- 9534892
TI  - Repeated open application tests (ROAT) in patients allergic to colophony-
      evaluated visually and with bioengineering techniques.
AB  - It is desirable to further evaluate the clinical relevance of a positive patch
      test. The repeated open application test (ROAT) has been suggested as such a
      supplementary method. To compare the results of patch testing with the outcome of
      ROATs, 13 colophony-sensitive subjects and 9 controls were patch-tested with
      colophony in a serial dilution test. Five microliters, of three concentrations of
      a colophony solution and the vehicle were then applied to small test areas on the
      lower arm, once daily for 2 weeks. Prior to each application, all test sites were
      examined visually and with bioengineering techniques. In the ROATs, 10/13
      colophony-sensitive subjects--but no controls--reacted to a 20% colophony
      solution, 4 also 1%. A correlation was found between the threshold concentration
      at patch testing and the outcome of ROATs. There was great variation in the
      reactivity in the ROATs. Objective measures for evaluating the ROAT reactions
      gave no further information than visual assessment.

PMID- 9534893
TI  - Grafting of in vitro cultured melanocytes onto laser-ablated lesions in vitiligo.
AB  - A variety of grafting procedures using autologous melanocytes have achieved
      promising results in the treatment of vitiligo. We here report on the preparation
      of an adequate graft recipient bed by pulsed Erbium-YAG laser skin ablation. In
      particular, for irregular lesions on delicate sites, which cannot be approached
      by utilization of suction blisters or dermabrasion, this technique may offer a
      distinct advantage.

PMID- 9534894
TI  - House dust mite antigen exposure of patients with atopic dermatitis of psoriasis.
AB  - We studied the amount of house dust antigen in the beds of 55 patients with
      atopic dermatitis, eleven patients with psoriasis and ten healthy volunteers
      using a commercial ELISA which can determine the amount of antigen from
      Dermatophagoides pteronyssinus, D. farinae and D. microseras expressed as
      nanogram (ng) antigen per gram of house dust. The World Health Organization has
      indicated that 10,000 ng house dust mite antigen per gram house dust can elicit
      an asthma attack in IgE-sensitized patients with asthma bronchiale. There are no
      recommendations for patients with atopic eczema. We observed no statistical
      significant differences between each group concerning the amount of house dust
      found in the beds or the amount of house dust mite antigen. However, there were
      very wide variations. Twenty-seven percent (15/55) of patients with atopic
      dermatitis and 27% (3/11) of psoriasis patients had levels of house dust mite
      antigen above 10,000 ng per gram of house dust compared with healthy volunteers
      (1/10). Half of the patients had a type I allergy to house dust mite antigen
      using prick tests. This group had a total serum IgE of 2,034 kU/I (median value)
      compared to 301 kU/I in the group without type I allergy to house dust mite
      antigen (p < 0.01). The exposure to house dust mite antigen was similar in the
      two groups. We conclude that only 1/4 of patients with atopic dermatitis are
      exposed to high levels of house dust mite antigen in their bed environment equal
      to what is found for patients with another scaling disorder (psoriasis). Patients
      who have an increased serum IgE have significantly increased type I allergy to
      house dust mite antigen even though their exposure is not different from patients
      with low IgE.

PMID- 9534895
TI  - Changes in sexual behaviour focusing on condom use in STD clinic attenders in
      Goteborg, Sweden, from 1989 to 1994--a questionnaire survey.
AB  - During the 4 years from 1989/1990 to 1994 an increase in the use of condoms was
      registered. A high frequency of condom failures was reported and probably
      reflects inappropriate use. More efforts should be made to educate people how to
      use the condom. The impact of alcohol intake as a risk factor for unsafe sex
      seems to be significant and should also be stressed in educational safer sex
      programmes. STD patients are a well-motivated group for information about safer
      sex and condom use. Health workers in STD clinics have an important task in this
      context.

PMID- 9534896
TI  - Unusual suction-like contact dermatitis due to ECG electrodes.

PMID- 9534897
TI  - Ectopic cilia in a Caucasian girl with atopic eczema.

PMID- 9534898
TI  - Malignant skin lesions on the legs and feet at a dermatological leg ulcer clinic
      during five years.

PMID- 9534899
TI  - Photoprotection in vitiligo and normal skin.

PMID- 9534900
TI  - Onychomycosis in HIV-infected patients.

PMID- 9534902
TI  - Exogenous pseudoxanthoma elasticum: a new case in an old farmer.

PMID- 9534901
TI  - Giant pendulous fibroma arising on the areola.

PMID- 9534903
TI  - Congenital multiple annular glomus tumors.

PMID- 9534904
TI  - Congenital leukonychia totalis in two brothers.

PMID- 9534905
TI  - Eosinophilic cellulitis (Wells' syndrome): treatment with minocycline.

PMID- 9534906
TI  - Disseminated cutaneous and eyelid metastases from a carcinoma of the breast.

PMID- 9534907
TI  - Alternating recombinant and natural alpha-interferon helps to prevent clinical
      resistance to interferon in cutaneous T-cell lymphoma treatment.

PMID- 9534908
TI  - Interleukin-12 as a target for modulation of the inflammatory response in asthma.

PMID- 9534909
TI  - Effects of damp and mould in the home on respiratory health: a review of the
      literature.
AB  - This review examines whether there is a direct or indirect relation between damp
      or mould in the home and respiratory health. Home dampness is thought to have
      health consequences because it has the potential to increase the proliferation of
      house-dust mites and moulds, both of which are allergenic. The results from the
      many studies conducted to investigate whether damp and mould are associated with
      health outcomes are difficult to compare because the methods of measuring
      exposures and health outcomes have not been standardized. However, the studies
      that have been conducted in children are probably the most reliable because the
      confounding effects of active smoking or occupational exposures are absent, and
      because the presence of symptoms of cough and wheeze have been consistently
      investigated in many studies. The increased risk of children having these
      symptoms if the home has damp or mould is fairly small with an odds ratio that is
      generally in the range 1.5-3.5, these estimates being statistically significant
      when the sample size has been large enough. This range is consistent with the
      measured effects of other environmental exposures which are considered important
      to health, such as environmental tobacco smoke or outdoor air pollutants. The
      potential benefits of reducing mould in the home have not been investigated, and
      the few studies that have investigated health improvements as a result of
      increasing ventilation or reducing damp in order to reduce house-dust mite levels
      suggest that this intervention is expensive, requires a large commitment, and is
      unlikely to be successful in the long term. This implies that houses need to be
      specifically designed for primary prevention of respiratory problems associated
      with indoor allergen proliferation rather than using post hoc procedures to
      improve indoor climate and reduce allergen load as a secondary or tertiary
      preventive strategy.

PMID- 9534910
TI  - A microtiter assay for activation of eosinophils. Simultaneous monitoring of
      eosinophil adhesion and degranulation.
AB  - A simple microtiter assay for eosinophil activation is described. The assay used
      1000-4000 eosinophils/microtiter well, and the design allows for a separate or
      simultaneous quantitative assessment of eosinophil adhesion to protein-coated
      microtiter wells and degranulation after stimulation with eosinophil-activating
      factors. The number of adherent eosinophils is quantified indirectly by
      expressing the amount of eosinophil cationic protein (ECP) extracted from the
      adherent fraction of cells in percentage of the total amount of ECP extracted
      from the cells added to the wells. Degranulation is quantified in the same way by
      expressing the amount of ECP or eosinophil protein X (EPX) released to the
      supernatant in percentage of the total amount of ECP or EPX. Known eosinophil
      activating agents such as PMA, interleukin (IL)-3, IL-5, GM-CSF, and platelet
      activating factor (PAF) all induced a time- and dose-dependent adhesion to
      albumin-coated wells, whereas L-PAF did not. Kinetic experiments showed that most
      adhesion occurred within the first 15-30 min, reaching a plateau around 60 min.
      After prolonged incubation, a decline in adhesion was detected. GM-CSF-induced
      adhesion was completely inhibited by incubation with monoclonal antibodies
      directed against the common beta 2-chain (CD18) of the LFA-1, Mac-1, p150,95
      complexes. Monoclonal antibodies against CD11a, CD11b, CD11c, VLA-4 ALFA, ICAM-1,
      VCAM-1, Sialyl-Le(x), ELAM-1, and LECAM had no inhibitory effect. Simultaneous
      monitoring of adhesion and degranulation after stimulation of eosinophils in
      albumin-coated wells with either PMA or GM-CSF showed that adhesion always
      preceded degranulation. Replacing the albumin coating of the microtiter wells
      with IgG or secretory IgA augmented both the spontaneous and the PMA- or GM-CSF
      stimulated responses. In conclusion, the assay allows dynamic evaluation of
      eosinophil activation and can be used to assess soluble eosinophil-activating
      factors as well as to study eosinophil activation by solid-phase-bound proteins.

PMID- 9534911
TI  - Is tyrosine kinase activation involved in basophil histamine release in asthma
      due to western red cedar?
AB  - Occupational asthma due to western red cedar is associated with histamine release
      from basophils and mast cells on exposure to plicatic acid (PA), but the
      mechanisms underlying this response remain unclear. Specific kinase inhibitors
      were used to study the role of tyrosine and serine/threonine kinases in PA
      induced histamine release from human basophils. Pretreatment with the tyrosine
      kinase inhibitor methyl 2,5-dihydroxy-cinnamate (MDHC) attenuated histamine
      release from basophils triggered by anti-IgE (29.8% inhibition; n = 15; P < 0.01)
      or grass pollen (48% inhibition; n = 6; P < 0.01). Inhibition was concentration
      dependent and could be reversed by washing the cells in buffer, while the
      inactive stereoisomer of MDHC did not affect histamine release. In contrast, the
      protein kinase C inhibitor staurosporine did not affect histamine release by
      either anti-IgE or grass pollen. Pretreatment with MDHC partially inhibited PA
      induced histamine release from basophils of 6/9 patients with red cedar asthma
      (25.4% vs 33.8%; P = NS). Staurosporine gave a similar level of inhibition of PA
      induced histamine release (25.3% vs 33.8%; P = NS). Thus, signal transduction of
      the human basophil Fc epsilon RI appears to depend upon tyrosine kinase
      activation, but not on protein kinase C (serine/threonine kinase) activation. The
      lack of specific effect on plicatic acid-induced histamine release in basophils
      obtained from patients with occupational asthma due to western red cedar suggests
      that tyrosine kinases are not as important in this disease as in atopic asthma,
      and is consistent with the view that histamine release in red cedar asthma is
      largely IgE-independent.

PMID- 9534912
TI  - Cross-reactivity between terrestrial snails (Helix species) and house-dust mite
      (Dermatophagoides pteronyssinus). I. In vivo study.
AB  - Clinical reports have suggested an unusual frequency in the number of patients
      with food allergy to snails who are also allergic to the house-dust mite (HDM).
      As allergy to HDM is one of the most frequent sensitizations in atopic patients
      of Western countries, evaluation of the relevance of the concomitant
      sensitization to Dermatophagoides pteronyssinus and to snails is an important
      consideration. To evaluate the responsibility of different snail components and
      of snail mites for inducing in vivo hypersensitivity in patients allergic to HDM,
      the in vivo reactivity of patients with clinical symptoms after ingestion of
      snails was assessed by skin prick tests with extracts and hemolymph from four
      different Helix species snails, and extracts from the snail parasitic mite,
      Riccardoella limacum. In addition, to obtain epidemiologic data on
      cosensitization to HDM and snails in allergic patients, the frequency of snail
      sensitization and its relationship to HDM sensitization were determined in a
      population of 169 allergic children. All patients allergic to snails had positive
      skin prick tests to the snail extracts and none to R. limacum extract. The number
      of positive skin reactions did not significantly differ whatever the species,
      snail part, or heating procedure used. The strongest reactions were obtained with
      Helix pomatia (Burgundy snail). Among the 169 prospectively tested children, 38
      had a positive prick test to snail extracts; 79% of the snail-sensitized children
      had sensitization to HDM; and 31% of the children allergic to HDM were found to
      be sensitized to snails. These results show that snail components, and not the
      mite R. limacum, were responsible for the in vivo hypersensitivity. These snail
      components reacting in vivo are present in different parts of snails, including
      the hemolymph. One-third of the children allergic to HDM were sensitized to
      snails without any previous ingestion of snails: this observation suggests that
      HDM was the sensitizing agent and that the cross-reaction could be clinically
      relevant in countries where eating snails is common.

PMID- 9534914
TI  - Allergy to feathers.
AB  - Skin prick test reactivity to commercial and self-made feather-allergen extracts
      was examined in 269 consecutive adult patients with suspected allergic cutaneous
      or respiratory symptoms who had been referred to a university clinic. Some 177
      subjects reacted to any inhalant allergen. Twenty-four (9% of the whole group and
      14% of those positive to any inhalant allergen) reacted to commercial feather
      extracts from ALK (Horsholm, Denmark), and 51 to any of the seven feather
      extracts used. Feather-mix RAST (Pharmacia, Sweden) was positive in three cases
      only. Skin prick test or CAP-RAST or both to house-dust mite were positive in 16
      of those 24 subjects positive to the commercial feather extracts, but in only 23
      of the 150 other atopic subjects (P < 0.001). A nasal challenge with a feather
      extract was made in 20 cases, always with negative result. In immunospot studies,
      concomitant allergy to feather-allergen extracts and house-dust mite could be
      demonstrated. Mite allergens in feather extracts were verified in RAST-inhibition
      studies. A clinically significant feather allergy was found in one patient only.
      The results suggest that true feather allergy is very rare, and most of the
      positive reactions seen in skin prick tests to feather extracts are probably
      caused by mite allergens present in feathers.

PMID- 9534913
TI  - Cross-reactivity between terrestrial snails (Helix species) and house-dust mite
      (Dermatophagoides pteronyssinus). II. In vitro study.
AB  - Epidemiologic and in vitro data have shown that the association of house-dust
      mite (HDM) allergy and snail allergy in the same patients was due to cross
      reactivity between HDM and snail allergenic components. However, the cross
      reacting allergen(s) have not yet been identified. In vitro reactivity of seven
      patients' sera to the various extracts and hemolymph of four different Helix
      snail species was analyzed by IgE detection and immunodots and Western blots.
      Cross-reactivity between snails and Dermatophagoides pteronyssinus was assessed
      by immunodot and ELISA inhibition in two patients. Heterologous inhibition of the
      snail immunodot and ELISA was observed in one serum. Western blotting showed a
      specific binding on all four snail species extracts; molecular weights of snail
      allergens ranged from < 21 to 200 kDa. Marked individual differences were
      observed in the seven sera under study; most sera demonstrated IgE recognition of
      multiple bands, illustrating that no single allergen is responsible for cross
      reactivity between snail and mite. These results confirm that cross-reactivity
      exists between snails of the Helix genus and HDM. This cross-reactivity,
      involving more than a single allergen, may be of clinical significance in atopic
      patients allergic to D. pteronyssinus. The identity of the cross-reacting
      allergens remains to be determined. Potential candidates include the thermostable
      minor allergens of D. pteronyssinus, tropomyosin and hemocyanin.

PMID- 9534915
TI  - Epitope mapping of the house-dust-mite allergen Der p 2 by means of site-directed
      mutagenesis.
AB  - Recombinant Der p 2, expressed in the baker's yeast Saccharomyces cerevisiae, was
      used as a tool to determine IgE- and monoclonal antibody (mAb)-binding sites on
      this allergen. For this purpose, mutant molecules were produced by application of
      site-directed mutagenesis. The amino-acid residues spanning cys21-cys27 and cys73
      cys78 were deleted, thus preventing loop formation through disulfide bonds.
      Charged residues in three predicted antigenic sites (residues 45-48, 67 + 69, and
      88-90) were replaced by alanine residues, IgE- and mAb reactivity to these
      mutants was compared to that to "wild type" Der p 2. Residues spanning cys73
      cys78 were involved in the antigenic binding site for mAb alpha DpX. Mutations in
      the areas adjacent to this loop (i.e., 67 + 69 and 88-90) had similar effects on
      this mAb (10- to 20-fold decreases in reactivity were observed), supporting the
      suggestion that these areas are involved in this antigenic structure. The area of
      residues 45-48 was shown to be involved in an epitope for mAb 2B12. The
      reactivity of mAb 7A1 was influenced by substitutions of residues 45-48 as well
      as 88-90. Deletion of the residues spanning cys21-cys27 resulted in decreased
      reactivity to three mAbs (10E11, alpha DpX, and 7A1). From these observations, it
      may be concluded that binding of different mAbs is influenced by the same
      mutations and that the binding of single mAbs is influenced by two or more
      mutations scattered over the allergen molecule. These findings can point in two
      directions: minor amino-acid changes result in disruption of the overall
      conformation of the allergen, or distant sites are close together in the three
      dimensional structure of the allergen. Decreased IgE reactivity was observed with
      all mutant molecules, varying between patients. The observed effects ranged from
      5- to 1000-fold. Deletion of the amino-acid residues spanning cys21-cys27 and
      cys73-cys78 had the strongest effect on IgE reactivity, where decreases up to
      1000-fold were observed. Such mutants might be useful tools to improve the safety
      of allergen-specific immunotherapy.

PMID- 9534916
TI  - Assay for detecting IgE and IgG antibodies against Candida albicans cell-wall
      mannan.
AB  - In the present study, we assayed mannan-specific IgE and IgG antibodies in
      samples of serum isolated from blood collected from adult patients with bronchial
      asthma, using a liquid-phase method with a polysaccharide, mannan (Mn), purified
      from Candida albicans (C. alb), and investigated the relationships of
      allergenicity among a crude extract of C. alb, purified Mn, and acid protease
      (AP), The correlations between the titers of anti-Mn A and anti-Mn B IgE and IgG
      were very strong, and the levels of inhibition of anti-Mn A IgE and IgG reactions
      by Mn A and Mn B were almost identical. Although no common allergenicity was
      observed between Mn A and AP because there was no correlation between the titers
      of anti-Mn A and anti-AP IgE, and no inhibition of the anti-Mn A IgE reaction by
      AP, both antigens were found to exist in crude C. alb. The level of inhibition of
      anti-crude C. alb IgG reaction by Mn A or Mn B was about 60%. Approximately 70%
      inhibition of the anti-Mn A IgE reaction was observed for eight different fungal
      allergen extracts, but no inhibition was observed for 11 of the other fungal
      allergen extracts tested. The above results indicate that common antigenicity was
      observed between Mn A and Mn B in the human IgE and IgG antibody production
      system, and the cross-allergenicity observed among some fungi was considered to
      be the result of the common antigenicity of Mn isoforms.

PMID- 9534917
TI  - Differential effects of new-generation H1-receptor antagonists in pruritic
      dermatoses.
AB  - In search of an improved treatment of pruritic dermatoses, we have studied
      azelastine, a novel H1-receptor antagonist, during a 2-week treatment period,
      using a double-blind, placebo-controlled design. The potent H1-antagonist
      cetirizine was used for comparison. Symptoms were recorded daily by the patients
      on a diary card, using a 4-point scale. The same parameters and adverse events
      were evaluated at weekly intervals, and global improvement was evaluated at the
      end of treatment. In all 230 evaluable patients with moderate to severe itching,
      azelastine caused an overall significant improvement in comparison to placebo (P
      = 0.02), with significance also for pruritus (P = 0.01 after 1 week and P = 0.02
      after 2 weeks). Both drugs reduced itching more effectively in urticaria than in
      atopic eczema. Azelastine was superior to cetirizine in reducing pruritus,
      whereas cetirizine caused a more marked reduction of whealing. Both drugs rarely
      caused fatigue and dry mouth, but taste perversion occurred only in azelastine
      treated patients (9.7%) and headaches only with cetirizine (10.4%). Therefore,
      the two H1-blockers exert differential effects on pruritus verses whealing and a
      distinctive adverse events pattern. The data also underline the low efficacy of
      antihistamines in atopic eczema, compared to urticaria.

PMID- 9534918
TI  - Changes in serum haptoglobin level after allergen challenge test in asthmatic
      children.
AB  - Bronchial asthma is characterized by airway inflammation, which underlies the
      phenomenon of bronchial hyperresponsiveness. Previous studies have shown that
      this correlates with the serum concentration of haptoglobin. The occurrence of
      the late asthmatic response (LAR) after an allergen challenge test is associated
      with airway inflammation. The objectives of this study were to examine serum
      levels of haptoglobin during the 24 h after allergen challenge and to compare
      changes between the subjects with and without LAR. We studied two groups of
      children with perennial asthma who developed the early asthmatic response (EAR)
      only (group I: n = 14), and EAR but also LAR (group II: n = 14) after an allergen
      (Dermatophagoides pteronyssinus) challenge test. Serum concentrations of
      haptoglobin were measured at baseline, at EAR, and at 2 h (recovery), 8 h (LAR),
      and 24 h after the challenge. Baseline levels were similar in the two groups
      (group I: 128 +/- 57 mg/dl; group II: 129 +/- 50 mg/dl). In group I, there was no
      significant change in the level at any time point; in contrast, the subjects in
      group II showed a relative fall (92 +/- 40 mg/dl) at 8 h, and an increase (161 +/
      79 mg/dl) at 24 h after the challenge. Our results indicate that the serum
      concentration of haptoglobin decreases at the time of LAR and is subsequently
      replenished during the ensuing time. Although further studies are needed, we
      think that haptoglobin may be inflused into the airways during the inflammatory
      process associated with LAR, and that this may be followed by "overshooting"
      production.

PMID- 9534919
TI  - Sense of smell in allergic and nonallergic rhinitis.
AB  - Hyposmia is a fairly common complaint in patients with long-continuing allergic
      or nonallergic rhinitis. Other factors such as aging, smoking, or nasal surgery
      may affect olfaction, but these have been little studied in rhinitis-related
      hyposmia. The purpose of this study was to measure and compare olfactory
      thresholds in 105 rhinitis patients and 104 healthy controls and to analyze
      possible relationships between the sense of smell and rhinitis, age, sex,
      smoking, prick-test results, nasal resistance, and history of nasal or paranasal
      surgery. The olfactory threshold was assessed with a commercially available kit
      of squeeze-bottle pairs. The most important variables associated with the sense
      of smell were determined with stepwise multiple regression analysis, and
      intergroup differences were assessed with analysis of variance. The reference
      interval of olfactory thresholds by age was estimated with regression analysis.
      Nasal resistance was measured by active anterior rhinomanometry. Age and rhinitis
      were the only variables with significant effect on the olfactory threshold in the
      whole series. Both the proportion of hyposmic persons and the degree of the
      impairment of the sense of smell were significantly higher in the rhinitis group
      than in the control group. The nonallergic patients' sense of smell was poorer
      than that of seasonal or perennial allergic rhinitis patients. A history of
      operations for nasal polyposis was associated with hyposmia, but operations for
      chronic maxillary sinusitis were not. Neither smoking habits nor sex were related
      to olfactory thresholds. In conclusion, hyposmia in rhinitis patients is partly
      attributable to age-related changes, but our results indicate that the disease
      itself impairs the sense of smell.

PMID- 9534920
TI  - Cat, dog, and house-dust-mite allergen levels of house dust in Finnish
      apartments.
AB  - The presence of indoor allergens in Finnish homes was studied for the first time.
      Dust samples (n = 30) were collected by vacuuming a 1 m2 area from a living-room
      carpet in 30 apartments divided into three groups: homes with cats (n = 10),
      homes with dogs (n = 10), and homes without pets (n = 10). The levels of major
      cat (Fel d 1), dog (Can f 1), and house-dust-mite (Der p 1) allergens were
      analyzed by two-site ELISA methods. Der p 1 levels were below the detection limit
      in all dust samples. In the homes with cats or dogs, Fel 1 d and Can f 1 levels
      ranged from 147 to 2800 micrograms/g (geometric mean 296 micrograms/g),
      respectively, 567 micrograms/g), and from 86 to 1400 micrograms/g (geometric mean
      296 micrograms/g), respectively, being slightly higher than those reported
      elsewhere. Low allergen levels, mainly below 3 micrograms/g were also detected in
      the homes without pets, indicating the transfer of allergens from place to place.
      However, in 25% of these samples, allergen levels exceeded the proposed threshold
      levels for cat or dog sensitization. The presence of pets was the most
      significant factor affecting cat and dog allergen levels in the house dust, and
      other factors, such as the amount of dust collected, residential time, and
      cleaning habits, had no or only a weak effect on allergen levels.

PMID- 9534921
TI  - Generation of clusters of free eosinophil granules (Cfegs) in seasonal allergic
      rhinitis.
AB  - Generation of clusters of free eosinophil granules (Cfegs), through lysis of
      eosinophils, has recently been proposed as a major paradigm for ultimate
      activation of airway mucosal eosinophils. In the present study involving patients
      with seasonal allergic rhinitis, we have investigated whether generation of Cfegs
      in the nasal mucosa is a feature of allergic rhinitis. Nasal mucosal biopsies
      were obtained before and late in a birch-pollen season, and were subjected to
      histochemical staining of eosinophil peroxidase. In biopsies obtained before the
      pollen season, a few, intact eosinophils were observed, and Cfegs were scarce. In
      biopsies taken during the pollen season, the numbers of eosinophils were
      increased about 10-fold (P < 0.05) and the Cfegs about 25-fold (P < 0.05). We
      conclude that generation of Cfegs is a significant feature of seasonal allergic
      rhinitis and that this process represents the ultimate activation of mucosal
      eosinophils in this disease.

PMID- 9534922
TI  - Occupational allergy caused by flowers.
AB  - We describe 14 consecutive patients with complaints due to the handling of
      flowers. The symptoms varied from allergic rhinoconjunctivitis and asthma to
      urticaria. Most patients had professions in the flower industry. Skin prick tests
      (SPT) were performed with home-made pollen extracts from 17 different flowers
      known to be the most commonly grown and sold in The Netherlands RAST against
      mugwort, chrysanthemum, and solidago was performed. The diagnosis of atopy
      against flowers was based on work-related symptoms due to the handling of
      flowers, positive SPT with flower extracts, and positive RAST. The concordance
      between SPT and case history was 74%, and that between SPT and RAST was 77%
      Extensive cross-sensitization was seen to pollen of several members of the
      Compositae family (e.g., Matricaria, chrysanthemum, solidago) and to pollen of
      the Amaryllidaceae family (Alstroemeria and Narcissus). Homemade flower extracts
      can be used to confirm IgE-mediated flower allergy. Mugwort can be used as a
      screening test for possible flower allergy. For most patients, the allergy led to
      a change of profession.

PMID- 9534923
TI  - Hypersensitivity pneumonitis due to an ultrasonic humidifier.
AB  - We describe a woman with hypersensitivity pneumonitis that was related to using a
      home ultrasonic humidifier. A micronodular infiltrate was seen in her chest
      radiograph. The inhalation challenge test was performed with the humidifier, and
      she exhibited a positive response. The cultures of the humidifier water grew
      Candida albicans, Rhodotorula spp., and Aspergillus spp. The test for
      precipitating antibodies against the humidifier water gave a positive response,
      and specific IgG, IgM, and IgA antibodies against extracts of A. fumigatus, C.
      albicans, and Rhodotorula spp. were demonstrated in the patient's serum by ELISA.
      A strong, dose-dependent inhibition of Rhodotorula IgG-ELISA by humidifier water
      was observed, suggesting that Rhodotorula might be the cause of hypersensitivity
      pneumonitis in this patient.

PMID- 9534924
TI  - Severe anaphylaxis to pine nuts.

PMID- 9534925
TI  - Detection of aspirin reactivity in patients with pyrazolones-induced skin
      disorders.

PMID- 9534926
TI  - Pollen exposure and sensitization.

PMID- 9534927
TI  - Allergic contact dermatitis to phenylephrine.

PMID- 9534928
TI  - Histopathology of dermatitis due to pseudoephedrine.

PMID- 9534929
TI  - Allergy to pine nuts.

PMID- 9534930
TI  - "Yours, thirsty for honesty, Ferenczi": some background to Sandor Ferenczi's
      pursuit of mutuality.

PMID- 9534931
TI  - The feud between Freud and Ferenczi over love.

PMID- 9534932
TI  - Ferenczi's trauma theory.

PMID- 9534933
TI  - Ferenczi's relaxation principle and the issue of therapeutic responsiveness.

PMID- 9534934
TI  - "As far as possible": discovering our limits and finding ourselves.

PMID- 9534935
TI  - Altered hypoxia-induced coronary vasodilatation in diabetic rabbit heart.
AB  - The effect of type 1 diabetes mellitus on hypoxia-induced coronary vasodilation
      was studied in isolated perfused rabbit hearts. Four groups of hearts were
      compared: control hearts from normal rabbits perfused with physiological buffer
      (5 mM glucose and 2 mM pyruvate added), hearts from alloxan-induced diabetic
      rabbits (same perfusion as control), hyperglycemic hearts from normal rabbits
      perfused with 22 mM glucose and 2 mM pyruvate, and hyperosmotic hearts from
      normal rabbits perfused with 5 mM glucose, 2 mM pyruvate, and 8.5 mM choline
      chloride. Hypoxia was produced by perfusion with a mixture of N2- and O2-
      saturated solutions. Endothelium-dependent and -independent dilators were also
      tested. Papaverine-induced coronary vasodilatation was unaltered, whereas that of
      serotonin and adenosine was significantly reduced in hyperglycemic and
      hyperosmotic hearts but not in diabetic hearts perfused with normoglycemic
      buffer. Hypoxia (PO2 from 515 +/- 86 to 131 +/- 24 mmHg; 1 mmHg = 133.3 Pa)
      caused a significant coronary vasodilatation in normal hearts (-66 +/- 3%). This
      vasodilatation was reduced slightly in diabetic (-45 +/- 7%, p < 0.05) and
      severely in hyperglycemic (-21 +/- 5%, p < 0.05) and hyperosmotic (-24 +/- 5%, p
      < 0.05) hearts. The adenosine-receptor antagonist 8-phenyltheophylline (10
      microM) reduced hypoxia-induced vasodilatation in normal and diabetic hearts.
      However, inhibition of prostaglandin synthesis with diclofenac (1 microM), which
      reduces hypoxia-induced vasodilatation in normal hearts, had no effect in
      diabetic hearts. In conclusion, alloxan-induced type 1 diabetes mellitus in
      rabbits is accompanied by a reduced coronary vasodilator response to hypoxia. The
      contribution of adenosine in this response is unaffected. However, the abated
      contribution of cyclooxygenase products may account for the reduced
      vasodilatation during hypoxia in this particular model.

PMID- 9534936
TI  - Heat stress induces rapid recovery of mechanical function of ischemic fatty acid
      perfused hearts by stimulating glucose oxidation during reperfusion.
AB  - Whole-body heat stress (HS) in rats leads to the accumulation of myocardial heat
      shock proteins and subsequent protection against ischemic injury in glucose
      perfused hearts. We determined whether HS treatment would confer protection
      against ischemia in hearts perfused with high levels of fatty acids. In addition,
      since fatty acids can potentiate ischemic injury by inhibiting glucose
      metabolism, the effects of HS on glucose utilization were also determined.
      Anesthetized rats were subjected to whole-body hyperthermia by raising body
      temperature to 41-42 degrees C 15 min. Twenty four hours later, their hearts were
      perfused with buffer containing either 11 mM glucose alone or 11 mM glucose and
      1.2 mM palmitate, and then subjected to ischemic conditions followed by
      reperfusion. In hearts perfused with glucose only, HS improved aortic flow
      (expressed as percent change from preischemic aortic flow) late into the
      reperfusion period. Rates of overall glucose utilization under these conditions
      were similar between control and HS hearts. When hearts were perfused with 1.2 mM
      palmitate, the benefits of HS on aortic flow occurred at the onset of the
      reperfusion period. This beneficial effect was associated with a significant
      increase in glucose oxidation. Our results show that HS induces a faster rate of
      recovery in fatty acid perfused hearts but does not offer more protection against
      ischemic damage when compared with hearts perfused with glucose as a sole
      substrate.

PMID- 9534938
TI  - Effect of disruption of the cytoskeleton on smooth muscle contraction.
AB  - The relationship between passive tension applied to aortic rings and the
      resulting increase in tissue length was nearly linear over the range of 1 to 15
      g. However, even with increasing tissue length, within the range of 1 to 10 g
      passive tension, the total active force generated upon stimulation was not
      significantly changed. These observations emphasize the great flexibility of the
      mechanism(s) underlying the contractile response of vascular smooth muscle with
      regard to changes in tissue preload and length. Neither the blockade of
      microtubule polymerization by colchicine nor the blockade of actin polymerization
      by cytochalasin B significantly changed the slope of the tissue length-preload
      curve, indicating no effect on the tissues' capacity to stretch at a given
      preload. With stimulation of the tissue at different levels of stretch,
      colchicine caused an increase in the initial fast component of active tension
      development, but partially blocked the secondary slow rise in tension.
      Cytochalasin B dramatically reduced the total contractile response at each
      preload studied, and this effect was confined almost exclusively to the secondary
      slow increase in tension. When tissues were cooled to cause complete dissolution
      of the microtubule network and then warmed in the presence of colchicine to
      prevent repolymerization of both the active and stable populations of
      microtubules, there was also a significant reduction in the slow component of
      contraction with no effect on the fast response. The partial blockade of
      synthesis of the microtubule-associated motor protein kinesin by application of
      an antisense oligonucleotide to aortae in situ or to aortic rings in tissue
      culture significantly reduced the contractile response to potassium
      depolarization. The results suggest that the microtubules and the actin filaments
      of the cytoskeleton play an active role in slow force development as opposed to a
      solely passive role based on the effect of the static, structural properties of
      these filaments on mechanical resistance. We propose that a tension-bearing
      element of the actin-containing cytoskeleton undergoes remodeling to adjust
      tension within the system. The microtubules could act either through the directed
      movement of the molecules involved in the transduction process or through the
      direct action of kinesin-mediated intracytoskeletal interactions in force
      development that involve a remodeling of the tension-bearing elements of the
      cytoskeleton.

PMID- 9534937
TI  - Reduced muscle lactate during prolonged exercise following induced plasma volume
      expansion.
AB  - To examine the effects of a dilutional mediated decrease in arterial O2 content
      on muscle metabolic and substrate behaviour during exercise, plasma volume was
      acutely expanded by either 14% (LOW) or 21% (HIGH) using a 6% dextran solution
      dissolved in saline (Macrodex) and compared with a control (CON) condition. The
      exercise protocol, performed by eight untrained males (VO2max = 45.2 +/- 2.2
      mL.kg-1.min-1, X +/- SE) and with the conditions randomized, was conducted for
      120 min at 46 +/- 4% VO2max. The content of inosine monophosphate determined on
      muscle tissue extracted from the vastus lateralis increased (p < 0.05) by 120 min
      of exercise (0.119 +/- 0.02 vs 0.493 +/- 0.19 mmol/kg dry weight) in CON. No
      effect of either LOW or HIGH expansion of plasma volume was found. Similarly,
      phosphocreatine content (mmol/kg dry weight), although reduced (p < 0.05) with
      exercise, was not different between the conditions at either 3 min (61.9 +/- 3.5,
      66.2 +/- 3.5, 64.3 +/- 2.1) or 120 min (52.5 +/- 6.3, 53.8 +/- 5.8, 59.4 +/- 5.5)
      of exercise. In contrast, both pyruvate and lactate were reduced (p < 0.05) by 3
      min of exercise in both LOW and HIGH compared with CON. The reduction in these
      metabolites with plasma volume expansion was not accompanied by an alteration in
      glycogen depletion rates. Steady-state VO2 was unaffected by acute hypervolemia.
      These results suggest that moderate exercise following an approximate 10%
      reduction in arterial O2 content can be performed without increasing the
      imbalance between ATP production and utilization rates. Since high energy
      phosphate transfer and glycolysis appeared not to be increased, mitochondrial
      respiration was apparently preserved by mechanisms as yet undetermined.

PMID- 9534939
TI  - Alpha and beta adrenoceptors mediate the inhibitory effect of epinephrine on the
      mucosal uptake of phenylalanine in the rat jejunum.
AB  - Although adrenergic agonists and antagonists have extensive clinical use, their
      effects on the intestinal absorption of amino acids have rarely been
      investigated. This work attempts to study the effect of epinephrine on the
      mucosal uptake of phenylalanine in the rat jejunum, using an in situ double
      perfusion technique that allows the intestine and its vasculature to be perfused
      simultaneously and respectively with the amino acid and the hormone and its
      antagonists. Epinephrine reduced, by about 30%, the mucosal transport of
      phenylalanine by activating alpha 1, alpha 2, and beta adrenergic receptors. The
      effect of the latter was not apparent however, until the alpha 2 receptors were
      blocked.

PMID- 9534940
TI  - Comparative effects of gallopamil and verapamil on the mechanical and
      electrophysiological parameters of isolated guinea-pig myocardium.
AB  - The effects of gallopamil, D600, a methoxy derivative of verapamil, on the
      mechanical and electrophysiological parameters of isolated guinea-pig myocardial
      preparations were compared with those of verapamil. Both gallopamil and verapamil
      produced concentration-dependent negative chronotropic and negative inotropic
      effects in isolated right atrial and right ventricular papillary muscles,
      respectively. The negative chronotropic and negative inotropic potencies of
      gallopamil were 7.2 and 4.3 times higher than those of verapamil, respectively.
      Gallopamil decreased the action potential duration of isolated papillary muscles
      without substantially affecting other action potential parameters, while
      verapamil decreased not only the action potential duration but also the maximum
      rate of rise and amplitude. In voltage-clamped single ventricular myocytes,
      gallopamil as well as verapamil decreased the L-type Ca2+ current amplitude. The
      potency orders for the shortening of the action potential duration and inhibitory
      effects of the L-type Ca2+ current amplitudes were verapamil > gallopamil. These
      results indicate that gallopamil has higher negative chronotropic and inotropic
      potency than verapamil as a result of factors other than L-type Ca2+ current
      inhibition.

PMID- 9534941
TI  - Hepatorenal reflex in the rat.
AB  - The possible existence of a hepatorenal reflex was evaluated in male Sprague
      Dawley rats. Sodium excretion was measured in two groups of six rats each, during
      the first 4 h following acute ingestion of a known amount of high salt chow (2.0
      2.5 mequiv. NaCl). Hourly excretion rates for sodium before surgery were compared
      with results following 7 days of recovery from either hepatic denervation (n = 6)
      or sham denervation (n = 6). Before denervation, hourly sodium excretion between
      the groups was not different. Following surgery for hepatic denervation, sodium
      excretion was 91% lower than presurgery values for the 1st h (p < 0.02) and 44%
      lower in the 2nd h (p < 0.04). Sham denervation caused no significant change in
      sodium excretion when compared with presurgery results. A test for completeness
      of denervation showed that norepinephrine concentration in liver tissue taken
      from denervated rats was 5.1 +/- 8 ng/g and that taken from sham rats was 22.8 +/
      1 ng/g (p < 0.001). These data demonstrate that the liver is essential for the
      normal postprandial excretion of sodium following ingestion of a high salt meal
      in rats.

PMID- 9534942
TI  - Myocardial fibrosis rather than hypertrophy induces diastolic dysfunction in
      renovascular hypertensive rats.
AB  - The aim of the present study was to evaluate the effect of interstitial fibrosis
      alone or associated with hypertrophy on diastolic myocardial function in
      renovascular hypertensive rats. Myocardial function was evaluated in isolated
      papillary muscle from renovascular hypertensive Wistar rats (RHT, n = 14),
      renovascular hypertensive rats treated with the angiotensin converting enzyme
      inhibitor (ACEI) ramipril, 20 mg.kg-1.day-1 (RHT RAM, n =14), and age-matched
      unoperated and untreated Wistar rats (CONT, n = 12). The ACEI treatment for 3
      weeks allowed the regression of myocyte mass and the maintenance of interstitial
      fibrosis. Myocardial passive stiffness was analyzed by the resting tension-length
      relationship. The myocardial fibrosis was evaluated by measuring myocardial
      hydroxyproline (Hyp) concentration and by histological studies of the myocardium
      stained with hematoxylin and eosin or picrosirus red. Left ventricular weight was
      significantly higher in RHT (0.97 +/- 0.12 g) compared with CONT (0.66 +/- 0.06
      g) and RHT RAM (0.69 +/- 0.14 g). The Hyp levels were 2.9 +/- 0.4, 3.4 +/- 0.3,
      and 3.8 +/- 0.4 micrograms/mg of dry tissue for the CONT, RHT, and RHT RAM,
      respectively. Perivascular and interstitial fibrosis were observed in RHT and RHT
      RAM groups. There were lymphononuclear inflammatory exudate and edema around
      arteries, involving adjacent myocytes in the RHT group. There was an increased
      passive stiffness in RHT and RHT RAM groups compared with the CONT group. In
      conclusion, our results indicate that the impaired diastolic function in the
      renovascular hypertensive rats is related to interstitial fibrosis rather than to
      myocardial hypertrophy.

PMID- 9534943
TI  - Nitric oxide participates in the corpus luteum regression in ovaries isolated
      from pseudopregnant rats.
AB  - In previous reports we found that nitric oxide is involved in corpus luteum
      regression in the rat by increasing prostaglandin F2 alpha synthesis during the
      luteolytic phase. In the present study we were interested in determining whether
      nitric oxide synthase activity is modulated with the corpus luteum development.
      For this purpose ovarian tissues obtained from pseudopregnant rats at different
      stages of pseudopregnancy, early, middle, and late, were used. Working with
      different doses of two competitive nitric oxide synthase inhibitors, NG
      monomethyl-L-arginine (L-NMMA) and aminoguanidine (AG), we investigated the
      possible role of endogenous nitric oxide in the regulation of prostaglandin F2
      alpha production by rat ovaries in the three different phases mentioned. We found
      that nitric oxide synthase activity diminishes with the corpus luteum development
      and that the calcium-independent activity was the predominant form of this enzyme
      in all stages studied. Endogenous nitric oxide increased prostaglandin F2 alpha
      synthesis only during the late phase of the corpus luteum. In the study of the
      possible role of nitric oxide regulating ovarian steroidogenesis, we found that L
      NMMA increased progesterone production and diminished prostaglandin F2 alpha
      synthesis in ovarian tissue from pseudopregnant rats in the late phase. These
      results suggest that nitric oxide could participate in the corpus luteum demise
      in the rat by modulating part of prostaglandin F2 alpha and progesterone
      production.

PMID- 9534944
TI  - Sites of nitric oxide (NO) actions in control of circular muscle motility of the
      perfused isolated canine ileum.
AB  - In the isolated intra-arterially perfused canine ileum, N omega -nitro-L-arginine
      (L-NNA, 3 x 10(-4) M) increased tonic and phasic motor activity of the circular
      muscle. As has previously been shown, L-NNA enhanced contractions to electrical
      field stimulation at sites proximal to the serosal electrodes and converted
      initial relaxation when present at distal sites to contraction. L-NNA shifted the
      acetylcholine dose-response curve to the left and amplified the response to low
      dose acetylcholine. Following L-NNA, addition of 10(-5) M sodium nitroprusside
      (NO donor) returned the tonic and phasic activity, the electrical field
      stimulation responses, and the acetylcholine dose-response curve to control
      values. Tetrodotoxin (TTX, 10(-6) M) increased tone (less than L-NNA) and
      abolished responses to both electrical field stimulation and motor activity
      induced by prior L-NNA. Subsequent L-NNA did not alter TTX-induced tonic motor
      responses. TTX also shifted the acetylcholine dose-response curve leftward and
      increased the responses to low-dose acetylcholine. After TTX, sodium
      nitroprusside returned the low-dose acetylcholine responses to control values
      and, after L-NNA, failed to restore them to control values. After L-NNA and TTX,
      sodium nitroprusside restored responses to low-dose acetylcholine to control
      values, Thus, removal of inhibition of the release of excitatory
      neurotransmitters, not removal of actions of NO on the muscle, accounted for the
      increases in tonic and phasic activity from L-NNA. Uninhibited release of
      excitatory transmitters augmented circular muscle responses to low-dose
      acetylcholine. TTX eliminated effects of excitatory transmitters, allowing
      exogenous NO to reduce low-dose acetylcholine contractions. No treatment affected
      the maximum responses to acetylcholine, produced by a contractile mechanism
      independent of muscle excitability and unaffected by exogenous NO or release of
      neurotransmitters.

PMID- 9534945
TI  - Role of fatty acid binding protein on hepatic palmitate uptake.
AB  - Expression of hepatic fatty acid binding protein (FABP) mRNA is regulated by
      growth hormone. In the absence of growth hormone, there is a 60% reduction in
      FABP mRNA levels (S.A. Berry, J.-B Yoon, U. List, and S. Seelig. J. Am. Coll.
      Nutr. 12:638-642. 1995). Previous work in our laboratory focused on the role of
      extracellular binding proteins in the hepatic uptake of long chain fatty acids.
      In the present study we were interested to determine the role of FABP in the
      transmembrane flux of long chain fatty acids. Using hepatocyte monolayers from
      control (n = 9) and hypophysectomized (n = 6) rats, we investigated the uptake of
      [3H]palmitate in the presence and absence of albumin. In the absence of albumin,
      total hepatocyte [3H]palmitate clearance rates from control (17.2 +/- 1.5
      microL.mg-1 protein.s-1; mean +/- SEM; n = 9) and hypophysectomized (15.5 +/- 2.1
      microL.mg-1 protein.s-1; n = 6) animals were similar (p > 0.05). In the presence
      of 2 microM albumin the total [3H]palmitate clearance rate from control
      hepatocytes (1.63 +/- 0.11 microL.mg-1 protein.s-1; n = 9) was significantly
      larger (40%) than from hepatocytes obtained from hypophysectomized (0.97 +/- 0.15
      microL.mg-1 protein.s-1; n = 6; p < 0.01) animals. SDS-PAGE electrophoresis
      revealed that plasma membrane FABP levels from control and hypophysectomized
      animals were similar. However, there was a 49% decrease in the cytosolic FABP
      levels of hepatocytes isolated from hypophysectomized as compared with control
      animals. The decreased cytosolic FABB levels paralleled the decrease in palmitate
      uptake. We conclude that in the absence of extracellular binding proteins the
      rate-limiting step in the overall uptake of long chain fatty acids is diffusion
      to the cell surface. However, in the presence of albumin, the rate of palmitate
      uptake is determined primarily by cytosolic FABP levels.

PMID- 9534946
TI  - Thymoquinone ameliorates the nephrotoxicity induced by cisplatin in rodents and
      potentiates its antitumor activity.
AB  - The effects of thymoquinone (TQ) on cisplatin-induced nephrotoxicity in mice and
      rats were studied. Oral administration of TQ (50 mg/L in drinking water) for 5
      days before and 5 days after single injections of cisplatin (5 mg/kg, i.v., in
      rats and 7 or 14 mg/kg, i.p., in mice) greatly ameliorated cisplatin-induced
      nephrotoxicity in both species. In rats, i.v. cisplatin caused 4- and 5-fold
      elevations in serum urea and creatinine, a 235% increase in urine volume, a 41%
      increase in kidney weight, 8.5-fold decrease in creatinine clearance, and
      extensive histological damage 5 days after treatment. In mice, similar
      alterations in kidney function were observed. TQ-induced amelioration of
      cisplatin nephrotoxicity was evident by significant reductions in serum urea and
      creatinine and significant improvement in polyuria, kidney weight, and creatinine
      clearance. The protective effects of TQ against cisplatin-induced nephrotoxicity
      in the rat were further confirmed by histopathological examination. To evaluate
      the possible modification of the antitumor activity of cisplatin by TQ, we
      studied their interaction in Ehrlich ascites carcinoma (EAC) bearing mice. The
      results revealed that TQ potentiated the antitumor activity of cisplatin. The
      current study suggests that TQ may improve the therapeutic index of cisplatin.

PMID- 9534947
TI  - Iron chelators of the pyridoxal isonicotinoyl hydrazone class. Relationship of
      the lipophilicity of the apochelator to its ability to mobilize iron from
      reticulocytes in vitro: reappraisal of reported partition coefficients.
AB  - The partition coefficients P between n-octanol and water of pyridoxal
      isonicotinoyl hydrazone and 34 analogues have been determined experimentally; the
      values indicate that the partition coefficients calculated for these compounds,
      and previously reported (P. Ponka, D.R. Richardson, J.T. Edward, and F.L. Chubb.
      Can. J. Physiol. Pharmacol. 72: 659-666. 1994; D.R. Richardson, E.H. Tran, and P.
      Ponka. Blood, 86: 4294-4306. 1994), are too low by 2-3 orders of magnitude. The
      calculations, using Rekker's additive method, failed because the molecules have
      two or more hydrophilic sites close together. More recent additive schemes
      (CLOGP, KOWWIN, ACD/LogP) also failed. The only reliable method was the semi
      empirical method of Hansch. This requires the experimental determination of the
      partition coefficient of at least one representative in each series of compounds
      of related structure. In the present paper, determination of log P of three
      representatives enabled us to calculate the partition coefficients of the other
      32 compounds with acceptable accuracy. The new results show that apochelators
      have maximum activity in releasing 59Fe from reticulocytes when they have log P =
      2.8 (P = 630), and not log P = 0 (P = 1), as reported by Ponka et al. (P. Ponka,
      D.R Richardson, J.T. Edward, and F.L Chubb. Can. J. Physiol. Pharmacol. 72: 659
      666 1994).

PMID- 9534948
TI  - Airway and lung tissue behaviour during endothelin-1 induced constriction in
      rats: effects of receptor antagonists.
AB  - Endothelin (ET) 1, a 21 amino acid constrictor peptide, is one of the most potent
      agonists of airway smooth muscle and acts on two different receptors, i.e., ETA
      and ETB receptors. Recently, it has been shown that there are species and organ
      differences in physiological roles of each ET receptor. In rats, however, the
      physiological roles of ET receptors remain to be clarified. We questioned whether
      ET-1 might affect airway and lung tissue via different ET receptor subtypes in
      rats. To answer this question, we investigated the effects of ET-1 on lung
      behaviour in anesthetized, open-chested, mechanically ventilated (f = 1 Hz, VT =
      9 mL/kg, PEEP = 3 cmH2O (1 cmH2O = 98.1 Pa)) rats in the absence or the presence
      of ETA and ETB selective antagonists, i.e., BQ-123 and BQ-788, respectively.
      Using alveolar capsules, we calculated lung elastance (EL), resistance of lung
      (RL), tissue (Rti), and airway (Raw), and hysteresivity (eta = 2 pifRti/EL) under
      control conditions and after intravenous administration of ET-1 (10(-8) mol/kg).
      ET-1 induced significant increases in RL, Rti, Raw, EL, and eta. BQ-123 did not
      affect ET-1 induced constriction, while BQ-788 significantly reduced delta RL,
      delta Rti, delta Raw, delta EL during ET-1 induced constriction. The effects of
      the combination of BQ-123 and BQ-788 were not different compared with BQ-788. Eta
      was not affected by BQ-123 and BQ-788. These data suggest that ETB, but not ETA,
      receptors may have significant physiological roles in rat lungs in response to ET
      1.

PMID- 9534949
TI  - Distribution of lactate and other ions in inactive skeletal muscle: influence of
      hyperkalemic lactacidosis.
AB  - The purpose of this study was to quantify changes in intracellular ion and acid
      base status resulting from the net flux of ions between perfusate and
      noncontracting muscle of differing fibre type in response to a perfusate that
      simulated the ionic conditions seen during intense exercise. Isolated rat hind
      limbs were perfused for 80 min with a bovine erythrocyte perfusate. Two series of
      experiments were performed: a normal perfusate (NP, n = 8) or a lactacidotic
      perfusate (LP, n = 8) that simulated arterial plasma and blood composition during
      intense exercise ([Lac-] = 11.0 mequiv. L-1, [K+] = 7.5 mequiv. L-1, and
      nonvolatile acid concentration = 71 nequiv.L-1). Net ion fluxes were determined
      by the arteriovenous difference across the hind limb and perfusate flow. Muscle
      ion concentrations were measured in the soleus (SOL), plantaris (PLT), and white
      gastrocnemius (WG) muscles. In the NP group, small net effluxes of K+ and Lac-
      from muscle were observed, but there was no net flux of Na+ or CI-. During LP, an
      initial rapid net influx of Lac- into muscle (151.2 +/- 9.4 mu equiv. min-1. 100
      g-1 at 5 min) was followed by a steady-state net influx of 24-37 mu equiv. min-1.
      100 g-1 between 20 and 60 min. During LP, net influx of Na+, CI-, and K+ was
      greater than during NP and average 58.0 +/- 11.2, 30.0 +/- 7.5, and 7.5 +/- 1.9
      mu equiv. min-1. 100 g-1, respectively. Following LP, muscle content of Na+ (WG
      only) and Lac- (WG, PLT, and SOL) was increased to a greater extent than
      following NP. The increased [Lac-]i contributed to an elevated [H+]i only in the
      slow oxidative SOL, consistent with the higher concentration of Lac-
      transporters, lower capacity to bind protons, and better regulation of [Na+]i in
      slow oxidative muscles. Calculated membrane potential (Em) was unchanged with NP
      but decreased on average from -76.2 +/- 1.2 to 63.4 +/- 2.2 mV with LP perfusion,
      with no difference among fibre types. The steady-state distribution of Lac-
      across the sarcolemma appears to be a function of both metabolic and transport
      processes; specifically, Lac- distribution was not fully explained by the
      membrane potential nor by the nonionic distribution of HLac as determined by the
      transmembrane pH gradient. It is concluded that inactive skeletal muscle modifies
      the ionic composition of blood perfusing the muscles. However, the altered ionic
      composition of these muscles may compromise their function as a result of an
      altered membrane potential in fast and slow muscles and increased [H+]i in slow
      oxidative muscles.

PMID- 9534950
TI  - Nitric oxide induced membrane hyperpolarization in the rat aorta is not mediated
      by glibenclamide-sensitive potassium channels.
AB  - Using conventional intracellular microelectrode techniques, the membrane
      potential (Em) of vascular smooth muscle cells in isolated segments of thoracic
      rat aorta was measured. The influence of exogenous and of endothelium-derived
      nitric oxide on the Em was assessed, and the involvement of glibenclamide
      sensitive channels in the observed membrane hyperpolarization was investigated.
      Exposures of the aorta strips to sodium nitroprusside (10(-8)-10(-5) M) caused a
      concentration-dependent and endothelium-independent hyperpolarization. Maximal
      hyperpolarization (5.7 +/- 0.4 mV) was obtained with 10(-5) M sodium
      nitroprusside. Acetylcholine (10(-8)-10(-5) M produced endothelium-dependent
      hyperpolarizations. At low concentrations, a slow Em change was elicited, which
      was sustained in the presence of the vasodilator. Higher concentrations of
      acetylcholine caused hyperpolarizations consisting of an initial transient peak
      followed by a more sustained component. Pre-exposure to Ng-nitro-L-arginine (L
      NNA, 2 x 10(-4) M), which depolarized Em by 2.5 +/- 0.7 mV, significantly
      attenuated the later component of hyperpolarizations, indicating that it is NO
      dependent. Glibenclamide (10-5 M) did not significantly affect the
      hyperpolarization induced by 10(-6)-10(-5) M sodium nitroprusside nor the
      maintained component of hyperpolarization induced by 10(-5) M acetylcholine. It
      is concluded that the hyperpolarization caused by exogenous or endogenous NO in
      the rat aorta is not mediated by activation of glibenclamide-sensitive potassium
      channels.

PMID- 9534951
TI  - Role of gender and vascular endothelium in rat aorta response to 17 beta
      estradiol.
AB  - Estrogen supplementation in postmenopausal women offers significant
      cardiovascular protection. The mechanism for this benefit is unclear but may be
      due to an interaction of estrogen with the blood vessel wall (vascular smooth
      muscle and endothelium). We examined the response of weight-matched female and
      male endothelium-intact and -denuded aortae to 17 beta-estradiol, its interaction
      with noradrenaline, and the effect of N-nitro-L-arginine. Estradiol produced
      relaxation responses that were significantly greater in female endothelium-intact
      preparations. This response was sensitive to N-nitro-L-arginine, while the
      response to 17 beta-estradiol in male endothelum-intact and both female and male
      endothelum-denuded preparations was resistant. Estradiol also inhibited
      contractions to noradrenaline, which was more pronounced in the female
      endothelium-intact aortic rings. These data imply that estradiol interacts
      preferentially with the female vascular endothelium, but there exists an
      endothelium-independent process that can also be activated in the male aorta.
      Further studies are warranted to elucidate these differential mechanisms.

PMID- 9534952
TI  - Potent blood pressure raising effects of activated coagulation factor XII.
AB  - A new pressor protein (NPP) in trypsin-activated human plasma was recently
      reported, whose blood pressure raising effects in bioassay rats are potentiated
      300% after treatment with angiotensin I converting enzyme inhibitors (captopril).
      Pure NPP showed good N-terminal sequence homology with coagulation factor beta
      FXIIa, and little of it was present in FXII-deficiency plasmas (> or = 99%, n =
      4). The present experiments confirm this in four additional FXII-deficiency
      plasmas. Further, (i) adding highly purified coagulation FXII, alpha FXIIa, or
      beta FXIIa fragment restores pressor activity to such plasmas, but only after
      activation with trypsin. (ii) Such requirement for trypsin suggests that no
      factor is structurally identical with NPP to begin with but that all can be
      activated to NPP. (iii) When injected directly by vein, only beta FXIIa is
      pressor, suggesting closest structural resemblance to NPP and (or) readiest
      endogenous conversion to NPP. (iv) NPP and beta FXIIa are cardiotonic: they both
      raise systolic pressure more than the diastolic, with a concomitant increase in
      heart rate. These observations support NPP's structural relationship with beta
      FXIIa and connect coagulation and blood pressure mechanisms in a new way, whose
      significance to the physiology and pathophysiology of blood pressure regulation
      remains to be established.

PMID- 9534953
TI  - In vivo production of cytokines and beta (C-C) chemokines in human recurrent
      herpes simplex lesions--do herpes simplex virus-infected keratinocytes contribute
      to their production?
AB  - Recurrent human herpes simplex lesions are infiltrated by macrophages and CD4 and
      CD8 lymphocytes, which secrete cytokines and chemokines. Vesicle fluid was
      examined by ELISA for the presence of cytokines and beta (C-C) chemokines. On the
      first day of the lesion, high concentrations of interleukin (IL)-1beta, and IL-6,
      moderate concentrations of IL-1alpha and IL-10, and low concentrations of IL-12
      and beta chemokines were found; levels of macrophage inflammatory protein (MIP)
      1beta were significantly higher than levels of MIP-1alpha and RANTES. At day 3,
      the concentrations of IL-1beta, IL-6, and MIP-1beta were lower, whereas the
      levels of IL-10, IL-12, and MIP-1alpha remained similar, and the level of tumor
      necrosis factor-alpha was now detectable. Herpes simplex virus infection of
      keratinocytes in vitro stimulated production of beta chemokines followed by IL-12
      and then IL-10, IL-1alpha, IL-1beta, and IL-6, indicating a potential role for
      these events in early recruitment, activation, and interferon-gamma production of
      CD4 cells in herpetic lesions.

PMID- 9534954
TI  - The prognostic relevance of the nonstructural 5A gene interferon sensitivity
      determining region is different in infections with genotype 1b and 3a isolates of
      hepatitis C virus.
AB  - Hepatitis C virus (HCV) RNA serum concentration, quasispecies complexity, and
      sequence and phylogenetic analysis of the nonstructural 5A gene (NS5A) interferon
      sensitivity determining region (ISDR) were determined in pretreatment serum
      samples from 47 patients with chronic hepatitis C (36 infected by HCV genotype 1b
      and 11 by 3a). Among HCV genotype 1b-infected patients, virus load was lower (P =
      .003) and the number of NS5A-ISDR amino acid changes was higher (P = .001) in
      long-term responders than in non-long-term responders, but there were no
      differences in quasispecies complexity. Multivariate analysis showed a close
      association between response to interferon and NS5A-ISDR phenotype. Phylogenetic
      analysis showed that isolates from non-long-term responders clustered apart from
      the majority of isolates from long-term responders. There was no association
      between virologic features and therapeutic response in HCV genotype 3a-infected
      patients. In conclusion, low virus load and mutant NS5A-ISDR phenotype are
      closely associated with long-term response to interferon in HCV genotype 1b- but
      probably not in 3a-infected patients.

PMID- 9534955
TI  - Absence of hepatitis C virus and detection of hepatitis G virus/GB virus C RNA
      sequences in the semen of infected men.
AB  - The identification of hepatitis C virus (HCV) in semen remains controversial and
      that of hepatitis G virus (HGV) or GB virus C (GBV-C) has never been
      investigated. Serum and semen from 90 anti-HCV-positive drug users were tested
      (27 infected with HIV) for HCV and HGV/GBV-C RNAs by polymerase chain reaction
      (PCR) assay, hybridization, and sequence analysis. Semen was processed into round
      cells, seminal plasma, and spermatozoa. Fifty-six patients were HCV-viremic, but
      HCV-RNA was not identified in their seminal fractions. However, PCR inhibitors
      were found in the semen of 34 of these men. Twenty-eight patients had HGV/GBV-C
      RNA in their blood and for 24 of them, ejaculates were available for analysis.
      HGV/GBV-C RNA was found in the seminal plasma of 6 of 12 samples free from PCR
      inhibitors. These results agree with the low risk of sexual transfer of HCV and
      provide preliminary evidence for the presence of HGV/GBV-C in semen.

PMID- 9534956
TI  - Experimental infection of chimpanzees with hepatitis G virus and genetic analysis
      of the virus.
AB  - Hepatitis G virus (HGV) was transmitted to 2 chimpanzees by inoculation with
      human plasma containing approximately 10(8) genome equivalents (GE) of HGV. The
      infection was characterized by the late appearance (weeks 10 and 11 after
      inoculation [pi]) of viremia that persisted throughout the 120-week follow-up.
      Serum HGV titer increased steadily until it plateaued at 10(6)-10(7) GE/mL.
      However, despite this relatively high titer, neither of the chimpanzees developed
      hepatitis. The sequence of the viral genome, recovered from each chimpanzee at
      week 77 pi, differed from that of the inoculum by 5 nt (2 aa) and 27 nt (2 aa).
      Two more chimpanzees were inoculated with a first-passage plasma pool. The
      chimpanzee inoculated with approximately 10(6.7) GE of HGV had viremia at week 1
      pi. However, the viral titer increased with the same kinetics as observed in the
      first passage. The second chimpanzee inoculated with approximately 10(4.7) GE of
      HGV had late appearance (week 7 pi) of viremia.

PMID- 9534957
TI  - Emergence of drug resistance during an influenza epidemic: insights from a
      mathematical model.
AB  - A model was developed for the emergence of drug-resistant influenza viruses
      during a closed population influenza epidemic that occurs in a single wave. The
      model was used to consider several treatment and chemoprophylaxis strategies and
      to determine their effects on the spread of the infection. The model predicts
      frequent emergence and transmission of drug-resistant viruses with certain
      treatment scenarios. According to the model, chemoprophylaxis of susceptible
      persons (without treatment of those who are symptomatic) may be the best way to
      reduce the force of an epidemic and to keep development of drug resistance low.
      The model predictions indicate that the relative transmissibility of resistant
      variants compared with wild type virus and the choice of the treatment or
      chemoprophylaxis strategy can be decisive for the spread of drug-resistant
      viruses, a feature that may be crucial in a pandemic.

PMID- 9534958
TI  - Passive protection of gnotobiotic calves using monoclonal antibodies directed at
      different epitopes on the fusion protein of bovine respiratory syncytial virus.
AB  - Two neutralizing, fusion-inhibiting bovine monoclonal antibodies (MAbs; B4 and
      B13) directed at different epitopes on the fusion protein of respiratory
      syncytial virus (RSV) protected the lungs of gnotobiotic calves from RSV
      infection. The MAbs were administered intratracheally 24 h before the calves were
      challenged with bovine RSV. A third, nonneutralizing, non-fusion-inhibiting but
      complement-fixing MAb, B1, provided no significant protection against infection,
      and the disease was not exacerbated. Pneumonic consolidation and mean virus titer
      in lung 7 days after challenge were significantly lower in calves given the
      fusion-inhibiting MAbs than in either control calves or those given MAb B1. The
      proliferative bronchiolitis with syncytial formation and widespread distribution
      of RSV antigen in the lower respiratory tract of the B1-treated and control
      calves were indistinguishable and typical of experimental bovine RSV infection.
      Syncytia were markedly absent, and little or no viral antigen was detected in
      either the B4- or B13-treated calves.

PMID- 9534959
TI  - Pathogen transmission in child care settings studied by using a cauliflower virus
      DNA as a surrogate marker.
AB  - Two regions of cauliflower mosaic virus DNA were designed as markers to study
      pathogen transmission in a child care home (CCH) and child care center (CCC) and
      in homes of CCC children. The DNA markers were stable for 1 month in the
      environment. The DNA markers were introduced into the environment through
      sensitized objects, and spread in the environment was traced by detection of the
      markers with polymerase chain reaction. The DNA markers spread rapidly in both
      the CCH and CCC after introduction and spread more rapidly in the toddler room
      than in the infant room of the CCC. Hand touching of contaminated areas was the
      major factor leading to spread of the markers. Hand washing and surface wiping
      decreased spread of the markers. The markers spread minimally from room to room
      in the CCC but were detected in the children's homes after introduction of
      markers in the CCC.

PMID- 9534960
TI  - Passive immunization with a human immunodeficiency virus type 1-neutralizing
      monoclonal antibody in Hu-PBL-SCID mice: isolation of a neutralization escape
      variant.
AB  - A monoclonal antibody (694/98-D) directed toward the V3 loop of human
      immunodeficiency virus type 1 (HIV-1) was evaluated for pre- and postexposure
      prophylaxis in SCID mice reconstituted with human peripheral blood lymphocytes
      (Hu-PBL-SCID). Fifty percent protection against the HIV-1LAI strain was obtained
      by preexposure administration of 1.32 mg/kg antibody. However, virus isolated
      from 1 mouse 3 weeks after passive immunization with 13.2 mg/kg antibody proved
      resistant to subsequent in vitro neutralization by 694/98-D. V3 loop sequence
      analysis of cloned virus revealed amino acid changes within the linear core
      epitope recognized by 694/98-D and in one flanking amino acid. Further evaluation
      of 694/98-D for postexposure prophylaxis in mice revealed that 694/ 98-D was
      effective when given 15 min after virus. However, efficacy declined to 50% if
      treatment was delayed to 1 h after virus inoculation. These studies point out
      some potential drawbacks of passive immunization with monoclonal antibodies.

PMID- 9534961
TI  - Improvement in cell-mediated immune function during potent anti-human
      immunodeficiency virus therapy with ritonavir plus saquinavir.
AB  - Inhibiting human immunodeficiency virus (HIV) replication with potent
      antiretroviral therapy may result in improved immune function, and this may lead
      to favorable outcomes, independent of changes in CD4+ lymphocyte count. The
      effect of combination protease inhibitor therapy (ritonavir plus saquinavir) on
      functional measures of cell-mediated immunity in 41 HIV-infected patients from
      one center of a multicenter trial was investigated. After 24 weeks, median plasma
      virus load decreased from 4.74 log10 copies/mL to below the detection limit of
      the assay (2.30 log10), and mean CD4+ lymphocyte count increased from 284
      cells/microL to 413 cells/microL. Proliferative responses to phytohemagglutinin
      developed in 21 of 34 patients in whom responses were absent at baseline.
      Increases were observed in interleukin-2, -12, and -10 production and in the
      expression of CD28 on CD8+ lymphocytes. Initiation of potent anti-HIV therapy
      results in a degree of immune restoration, suggesting that HIV-induced immune
      suppression is a dynamic and potentially reversible process.

PMID- 9534962
TI  - gp41 envelope protein of human immunodeficiency virus induces interleukin (IL)-10
      in monocytes, but not in B, T, or NK cells, leading to reduced IL-2 and
      interferon-gamma production.
AB  - The effect of extracellular domain of human immunodeficiency virus (HIV-1)
      transmembrane glycoprotein gp41 on interleukin (IL)-10, IL-2, interferon (IFN)-y,
      IL-4, and tumor necrosis factor-alpha production by human peripheral blood
      mononuclear cells (PBMC) was assessed by ELISA. Rapid gp41-induced increase of IL
      10 production was detected in resting PBMC and isolated monocytes but not in B,
      T, or NK cells. Furthermore, gp41 also enhanced IL-10 production in
      staphylococcal enterotoxin B-stimulated PBMC, while synthesis of IL-2, IFN-gamma,
      and IL-4 in these cells was down-modulated. Kinetic studies revealed that
      increased IL-10 production preceded reduction of IL-2, indicating the possible IL
      10 regulatory role in the gp41-induced down-modulation of this cytokine. Anti-IL
      10 antibody reversed almost completely the gp41 inhibitory effect on IL-2
      production. In this study, HIV-1 gp41 was a potent modulator of cytokine
      production by PBMC, in particular by increasing IL-10 secretion from normal
      monocytes/macrophages and consequently down-regulating IL-2 and IFN-gamma.

PMID- 9534963
TI  - Immunomodulatory treatment of Mycobacterium avium complex bacteremia in patients
      with AIDS by use of recombinant granulocyte-macrophage colony-stimulating factor.
AB  - Eight AIDS patients with Mycobacterium avium complex (MAC) bacteremia were
      randomized to receive azithromycin with or without granulocyte-macrophage colony
      stimulating factor (GM-CSF) for 6 weeks to examine the effect of GM-CSF
      administration on clearance of mycobacteremia and on monocyte function.
      Superoxide anion production was significantly increased ex vivo in monocytes from
      patients receiving GM-CSF but not in those from patients receiving azithromycin
      alone. Relative to monocytes obtained from untreated healthy controls, median
      differences in viable intracellular MAC at 2, 4, and 6 weeks were -0.76, -0.94,
      and -0.47 log10 cfu/mL of lysate for cells from patients receiving GM-CSF versus 
      0.15, -0.11, and -0.19 log10 cfu/mL for cells from patients receiving
      azithromycin alone. Although no effect on mycobacteremia was detected, the
      administration of GM-CSF to AIDS patients with MAC bacteremia resulted in
      activation of their blood monocytes, as evidenced by increased superoxide anion
      production and enhanced mycobactericidal activity. GM-CSF deserves further
      investigation in the treatment of mycobacterial infections.

PMID- 9534964
TI  - Reduced expression of interleukin-8 receptors A and B on polymorphonuclear
      neutrophils from persons with human immunodeficiency virus type 1 disease and
      pulmonary tuberculosis.
AB  - The expression of the two human interleukin (IL)-8 receptors, designated IL-8RA
      (CXCR-1) and IL-8RB (CXCR-2), on the surface of whole blood polymorphonuclear
      leukocytes (PMNL) was determined by use of receptor-specific monoclonal
      antibodies and flow cytometry. Sixteen subjects each were included in 4 study
      groups: healthy blood donors (ND), patients with pulmonary tuberculosis (TB),
      human immunodeficiency virus type 1-seropositive patients (HIV), and HIV-1
      seropositive subjects with pulmonary tuberculosis (HIV/TB). A significant
      reduction in the percentage of PMNL expressing IL-8RA and IL-8RB and in their
      respective fluorescence intensities was found in TB, HIV, and HIV/TB groups
      compared with that obtained for the ND group. The greatest down-regulation of
      both receptors occurred in the HIV/TB group. Furthermore, associated with this
      reduced expression of IL-8 receptors was impairment of both intracellular calcium
      flux and migration of PMNL in response to IL-8 in a group of HIV/TB patients
      compared with that in healthy persons.

PMID- 9534965
TI  - Neurosyphilis during the AIDS epidemic, San Francisco, 1985-1992.
AB  - To investigate the epidemiology and clinical spectrum of neurosyphilis in a
      population with high rates of coexisting syphilis and human immunodeficiency
      virus (HIV) infection, a retrospective analysis of cases in all San Francisco
      hospitals from 1985 to 1992 was conducted. Neurosyphilis was defined by a newly
      reactive cerebrospinal fluid VDRL; 117 patients with neurosyphilis were
      identified. The median age was 39 years, 91% were male, 74 (63%) were white, and
      75 (64%) were HIV-infected. Thirty-eight (33%) presented with an early
      symptomatic neurosyphilis syndrome. Six (5%) had late neurosyphilis. Thirty-eight
      (32%) patients were asymptomatic, and 35 (30%) had findings attributable to
      coexisting neurologic diseases. Patients demonstrated high serum nontreponemal
      (VDRL) titers (median, 1:128) at neurosyphilis presentation. In contrast to the
      findings from the preantibiotic era, neurosyphilis was identified in young
      patients most often with HIV coinfection, and early symptomatic syndromes were
      identified more frequently than late neurosyphilis syndromes.

PMID- 9534966
TI  - Treponema pallidum, lipoproteins, and synthetic lipoprotein analogues induce
      human immunodeficiency virus type 1 gene expression in monocytes via NF-kappaB
      activation.
AB  - Syphilitic genital ulcers are cofactors for the bidirectional transmission of
      human immunodeficiency virus (HIV). U937 human promonocytic cells chronically
      infected with HIV-1 (U1 cells) or transiently transfected with wild type or
      mutant HIV long terminal repeat (LTR) reporter constructs were used to examine
      mechanisms that likely underlie Treponema pallidum-induced immune cell activation
      and consequent induction of HIV. Virulent T. pallidum, a representative native
      treponemal lipoprotein (NTp47), or synthetic lipoprotein analogues (lipopeptides)
      all induced HIV replication in U1 cells. These stimuli also induced HIV gene
      expression from a wild type HIV LTR. HIV gene expression correlated with the
      translocation of NF-kappaB, and mutations within the NF-kappaB binding sites of
      the HIV LTR abrogated HIV gene expression. This study implicates treponemal
      lipoproteins as key mediators of immune cell activation and provides insights
      into the cellular and molecular bases for enhanced HIV transmission in syphilitic
      persons.

PMID- 9534967
TI  - Development of quinolone-resistant Campylobacter fetus bacteremia in human
      immunodeficiency virus-infected patients.
AB  - Campylobacter fetus subspecies fetus has been recognized as a cause of systemic
      illness in immunocompromised hosts, including relapsing bacteremia in human
      immunodeficiency virus (HIV)-infected patients. Acquired resistance to quinolone
      therapy, while reported for a variety of bacteria, including Campylobacter
      jejuni, has not been previously documented for C. fetus. Two cases of quinolone
      resistant C. fetus bacteremia were detected in HIV-infected patients. Cloning and
      nucleotide sequencing of the C. fetus gyrA gene in the 2 resistant isolates
      demonstrated a G-to-T change that led to an Asp-to-Tyr amino acid substitution at
      a critical residue frequently associated with quinolone resistance. In addition,
      comparison of the pre- and posttreatment isolates from 1 patient documented outer
      membrane protein changes temporally linked with the development of resistance.
      Relapsing C. fetus infections in quinolone-treated HIV-infected patients may be
      associated with the acquisition of resistance to these agents, and this
      resistance may be multifactorial.

PMID- 9534968
TI  - Inhibition of Helicobacter pylori and Helicobacter mustelae binding to lipid
      receptors by bovine colostrum.
AB  - Helicobacter pylori, the etiologic agent of chronic-active gastritis and duodenal
      ulcers in humans, and Helicobacter mustelae, a gastric pathogen in ferrets, bind
      to phosphatidylethanolamine (PE), a constituent of host gastric mucosal cells,
      and to gangliotetraosylceramide (Gg4) and gangliotriaosylceramide (Gg3). The
      effect of a bovine colostrum concentrate (BCC) on the interaction of H. pylori
      and H. mustelae to their lipid receptors was examined. BCC blocked attachment of
      both species to Gg4, Gg3, and PE. Partial inhibition of binding was observed with
      native bovine and human colostra. BCC lacked detectable antibodies (by
      immunoblotting) to H. pylori surface proteins (adhesins). However, colostral
      lipid extracts contained PE and lyso-PE that bound H. pylori in vitro. These
      results indicate that colostrum can block the binding of Helicobacter species to
      select lipids and that binding inhibition is conferred, in part, by colostral PE
      or PE derivatives. Colostral lipids may modulate the interaction of H. pylori and
      other adhesin-expressing pathogens with their target tissues.

PMID- 9534969
TI  - A nationwide case-control study of Escherichia coli O157:H7 infection in the
      United States.
AB  - Risk factors for Escherichia coli O157:H7 infection were investigated in a case
      control study at 10 medical centers throughout the United States. Among 73 case
      patients and 142 matched controls, exposures in the 7 days before illness
      associated with E. coli O157:H7 infection in univariate analysis included
      consumption of hamburger (matched odds ratio [MOR], 3.8; 95% confidence interval
      [CI], 1.9-7.9), undercooked hamburger (MOR, 4.5; 95% CI, 1.6-12.2), or hot dogs
      (MOR, 2.2; 95% CI, 1.1-4.4); eating at a fast-food restaurant (MOR, 2.3; 95% CI,
      1.1-4.6); drinking unchlorinated well water (MOR, 2.4; 95% CI, 1.1-5.7); swimming
      in a pond (MOR, 5.4; 95% CI, 1.1-26.0); and having a household member with
      diarrhea (MOR, 11.9; 95% CI, 2.7-53.5). In multivariate analysis, only eating
      undercooked hamburger remained associated with infection. Seven (8%) of 93
      patients developed hemolytic uremic syndrome and 1 died. Prevention strategies
      aimed at modifying risk factors may help to reduce the risk of infection with E.
      coli O157:H7.

PMID- 9534970
TI  - Identification of a novel insertion element, IS1548, in group B streptococci,
      predominantly in strains causing endocarditis.
AB  - Hyaluronidase has been postulated to be a virulence factor in group B
      streptococci (GBS). No hyaluronidase activity was found in 15 of 50 GBS isolates
      from adults studied. Most of these hyaluronidase-negative strains belonged to
      serotype III. In strains lacking hyaluronidase activity, an insertion of 1317
      nucleotides was found in the hyaluronidase gene. The fragment was cloned and
      sequenced and found to have characteristics of a novel insertion sequence,
      designated IS1548. As well as in GBS serotype III, this sequence was found in 3
      of 6 serotype II isolates and in all 10 group A streptococcal strains (GAS)
      tested. Homologies were found with repeated sequences in Streptococcus pneumoniae
      and with H repeats in Escherichia coli. All GBS strains harboring IS1548 and some
      GAS strains had one copy of IS1548 located downstream of the C5a peptidase gene.
      IS1548 was present in 9 of 13 GBS isolates from blood in endocarditis patients
      and in 3 of 22 vaginally colonizing strains.

PMID- 9534971
TI  - Induction of beta2 integrin-dependent neutrophil adhesion to human alveolar
      epithelial cells by type 1 Streptococcus pneumoniae and derived soluble factors.
AB  - Pneumonia caused by Streptococcus pneumoniae is characterized by neutrophil
      infiltration and variable epithelial injury. Neutrophil adhesion to alveolar
      epithelial pneumocytes (A549) was measured and demonstrated to be dose-dependent
      following preincubation of these (A549) pneumocytes with type 1 S. pneumoniae.
      Adhesion peaked at a bacteria-to-epithelial cell ratio of 5:1 after a 4-h
      incubation but was absent after 2 h and without FMLP. Filtered conditioned media
      (CM) from pneumococci cultured with (CM+) or without (CM-) epithelial cells were
      tested. CM+ induced significant adhesion in the absence of FMLP (P < .001); CM-
      had no effect. In the presence of FMLP, adhesion induced by both media was
      significantly greater than by FMLP alone (P < .001) and was significantly blocked
      (P < .01) by antibodies to CD11b and CD18. CM+ upregulated epithelial
      intercellular adhesion molecule 1 but CM- did not. These data provide new
      information concerning the interactions of S. pneumoniae, alveolar epithelial
      cells, and neutrophils.

PMID- 9534972
TI  - Minimum protective serum concentrations of pneumococcal anti-capsular antibodies
      in infant rats.
AB  - Infant rats were passively immunized to determine the protective capacity of
      pneumococcal anticapsular antibodies. Animal-passaged strains of Streptococcus
      pneumoniae serotypes 1, 4, 5, 6b, 7f, 9v, 14, 18c, 19f, and 23f were used as
      challenge inocula (1-1500 cfu) in a model of pulmonary infection that resulted in
      bacteremia, meningitis, and death. From untreated control animals, histologic
      sections of lung demonstrated infiltrative pneumonia and lung homogenate cultures
      grew S. pneumoniae at concentrations of 10(3)-10(8) cfu per gram of lung tissue.
      A type-specific anti-capsular antibody serum concentration of 0.1-1.15 microg/mL
      resulted in a statistically significant reduction in mortality compared with the
      reduction in untreated controls, except for serotype 14, which required 2.32
      microg/mL for a significant reduction in mortality. The serum antibody level that
      provided 50% reduction in mortality ranged from 0.1-3.5 microg/mL for all
      serotypes.

PMID- 9534973
TI  - Role of emm and mrp genes in the virulence of group A streptococcal isolate 64/14
      in a mouse model of skin infection.
AB  - The virulence of group A streptococcal isolate 64/14 and paired isogenic mutants
      in which either the emm or mrp gene had been insertionally inactivated was
      compared in mice. Loss of expression of the emm gene product resulted in a
      significant loss of virulence when the isolate was injected into the skin but had
      no significant difference when injected intraperitoneally. By contrast,
      inactivation of the mrp gene caused the organism to be more virulent in the skin,
      while having no significant effect intraperitoneally. An isogenic mutant, in
      which the mga gene was inactivated and neither the emm gene nor the mrp gene was
      expressed, demonstrated no significant difference in virulence from the wild type
      organism. Organisms recovered from the spleen of mice lethally infected with the
      mga mutant expressed all Mga-regulated IgG-binding gene products despite the
      presence of the spectinomycin-resistance cassette, which was used to inactivate
      the mga gene, in its original position.

PMID- 9534974
TI  - Serotype distribution of invasive group B streptococcal isolates in Maryland:
      implications for vaccine formulation. Maryland Emerging Infections Program.
AB  - Invasive group B streptococcal (GBS) infection is a major health problem among
      infants and adults. The formulation of GBS vaccines depends on knowledge of the
      GBS serotype distribution. Serotype V GBS infection appears to have recently
      emerged, suggesting that the serotype distribution changes over time. GBS
      isolates from 210 pediatric patients, 23 pregnant women, and 314 nonpregnant
      adults with invasive infection in Maryland were studied. The predominant
      serotypes from infants with early-onset disease were as follows: serotype III,
      38% of isolates; serotype Ia, 36%; serotype V, 13%; and serotype II, 11%.
      Although the majority (60%) of isolates among infants with late-onset infection
      were serotype III, serotype Ia (23%) was also common. The predominant serotype
      among isolates from nonpregnant adult patients was serotype V, accounting for 29%
      of the isolates. The serotype distribution differs between pediatric patients and
      adults and is changing over time. The inclusion of a relatively small number of
      serotypes in a GBS vaccine could provide protection against the vast majority of
      isolates.

PMID- 9534975
TI  - Acquisition, carriage, and transmission of pneumococci with decreased antibiotic
      susceptibility in young children attending a day care facility in southern
      Israel.
AB  - The prevalence and transmission of antimicrobial drug-resistant pneumococci was
      studied in 48 children attending a day care facility in southern Israel.
      Nasopharyngeal cultures were obtained every 2 weeks for 10 months, and antibiotic
      susceptibility of isolates was determined by disk diffusion and E-test.
      Relatedness of isolates was investigated by capsular typing, ribotyping, and
      arbitrarily primed polymerase chain reaction. Pneumococci were recovered during
      362 (63%) of 573 fortnights, and 219 (60%) of these isolates showed decreased
      susceptibility to at least one drug; 154 (43%) were intermediately susceptible to
      penicillin and 51 (14%) were multiresistant. Combining the different typing
      methods showed that a limited number of clones circulated in the facility. Clones
      exhibiting decreased antibiotic susceptibility (especially 23F, intermediately
      susceptible to penicillin and resistant to trimethoprim-sulfamethoxazole, and
      multiresistant 6B) were more frequently isolated and persisted longer than did
      fully susceptible clones. By multivariate analysis, carriage of organisms with
      decreased antibiotic susceptibility was associated with young age, female sex,
      winter season, and exposure to antimicrobial drugs during the previous month.

PMID- 9534976
TI  - Differential immune responses to staphylococcal enterotoxin B mutations in a
      hydrophobic loop dominating the interface with major histocompatibility complex
      class II receptors.
AB  - Bacterial superantigens, such as staphylococcal enterotoxin B (SEB), can trigger
      acute pathologic effects in humans. A hydrophobic loop on the surface of SEB and
      other bacterial superantigens, centered around a conserved leucine (L45) residue,
      is essential for binding to class II major histocompatibility complex molecules.
      Single residue changes of wild type SEB, designated Q43P, F44P, or L45R, resulted
      in nonlethal proteins at a dose equivalent to 30 murine LD50 of SEB. Relative to
      SEB, the mutant proteins did not elevate serum concentrations of proinflammatory
      cytokines in mice and caused minimal proliferation of human lymphocytes. Anti-SEB
      titers of mice immunized with Q43P, F44P, L45R, or SEB were similar and protected
      77%-100% of animals against a lethal SEB challenge. Levels of toxin-specific
      IgG1, IgG2a, IgG2b, and IgG3 in mice immunized with SEB, Q43P, or F44P were
      equivalent, but animals immunized with L45R had significantly elevated levels of
      IgG2a and IgG2b. Vaccines against staphylococcal superantigens should focus on
      this critical leucine residue.

PMID- 9534977
TI  - Persistent infection with small colony variant strains of Staphylococcus aureus
      in patients with cystic fibrosis.
AB  - In a 34-month prospective study to determine the prevalence of Staphylococcus
      aureus small colony variants (SCVs) in cystic fibrosis (CF) patients, S. aureus
      SCVs or SCVs plus normal S. aureus were recovered from 26 of 78 patients; 27
      patients harbored only normal S. aureus. By pulsed-field gel electrophoresis,
      clonal identity was demonstrated of SCV and normal strains isolated at the same
      time and of multiple S. aureus SCV and normal strains in consecutive specimens
      from individual patients. All S. aureus SCVs were resistant to antifolate
      antibiotics, while the corresponding parent strains were susceptible, and in 11
      of 12 SCV/normal pairs, gentamicin was less active against S. aureus with the SCV
      phenotype than against the normal isolate. Analysis of the underlying
      auxotrophism of SCVs revealed hemin, thymidine, and/or menadione dependencies.
      Thus, S. aureus SCVs are highly prevalent in respiratory secretions of CF
      patients, persist over extended periods, and may contribute to S. aureus
      persistence in CF patients.

PMID- 9534978
TI  - Expression of katG in Mycobacterium tuberculosis is associated with its growth
      and persistence in mice and guinea pigs.
AB  - The molecular mechanisms associated with the pathogenesis of tuberculosis are not
      well understood. The present study evaluated the role of catalase-peroxidase as a
      potential virulence factor for Mycobacterium tuberculosis. Growth and persistence
      of M. tuberculosis H37Rv in intravenously infected BALB/ c mice were compared
      with katG-deleted, isoniazid-resistant M. tuberculosis H37RVINHR. Transformation
      of M. tuberculosis H37Rv (TBkatG) or Mycobacterium intracellulare (MACkatG) genes
      into M. tuberculosis H37RvINHR restored its catalase-peroxidase activities and
      the ability of the recombinants to persist in spleens of mice and guinea pigs.
      Transformation with the TBkatG gene with the codon 463 R-->L mutation also
      restored catalase-peroxidase activity and enhanced persistence. However,
      transformants with the codon 275 T-->P mutant expressed low levels of enzymatic
      activity and failed to persist in guinea pig spleen, although they did survive in
      mouse tissues. These results indicate that KatG contributes to the ability of M.
      tuberculosis to grow and survive within the infected host tissues.

PMID- 9534979
TI  - The flanking region sequences of the 15-kDa lipoprotein gene differentiate
      pathogenic treponemes.
AB  - The species Treponema pallidum includes three subspecies (pallidum, pertenue, and
      endemicum) that cause syphilis, yaws, and bejel, respectively. A closely related
      species, Treponema paraluiscuniculi, is the etiologic agent of venereal syphilis
      in rabbits but does not infect humans. Although these treponemes cause distinct
      diseases, no laboratory method for differentiation has been reported. Genetic
      signatures were defined in the 5' and 3' flanking regions of the 15-kDa
      lipoprotein gene (tpp15) that distinguish the human pathogens and T.
      paraluiscuniculi, as well as distinguishing T. pallidum subsp. pallidum from the
      causes of human nonvenereal treponematoses. A single Eco47III restriction site in
      the 5' flanking region differentiates T. pallidum subsp. pallidum from the other
      subspecies and species, and an XcmI site in the 3' flanking region differentiates
      T. paraluiscuniculi from the human pathogens. Polymerase chain reaction methods
      and restriction polymorphism were used to analyze 27 strains of pathogenic
      Treponema species.

PMID- 9534980
TI  - An outbreak of Brainerd diarrhea among travelers to the Galapagos Islands.
AB  - In 1992, an outbreak of chronic diarrhea occurred among passengers on a cruise
      ship visiting the Galapagos Islands, Ecuador. Passengers (548) were surveyed, and
      stool and biopsy specimens from a sample who reported chronic diarrhea were
      examined. On completed questionnaires, returned by 394 passengers (72%), 58 (15%)
      reported having chronic diarrhea associated with urgency (84%), weight loss
      (77%), fatigue (71%), and fecal incontinence (62%). Illness began 11 days
      (median) after boarding the ship and lasted 7 to >42 months. Macroscopic and
      histologic abnormalities of the colon were common, but extensive laboratory
      examination revealed no etiologic agent. No one responded to antimicrobial
      therapy. Patients were more likely than well passengers to have drunk the ship's
      unbottled water or ice before onset of illness and to have eaten raw sliced
      fruits and vegetables washed in unbottled water. Water handling and chlorination
      on the ship were deficient. Outbreaks of a similar illness, Brainerd diarrhea,
      have been reported in the United States. Although its etiology remains unknown,
      Brainerd diarrhea may also occur among travelers.

PMID- 9534981
TI  - Effects of aerosolized synthetic surfactant, atovaquone, and the combination of
      these on murine Pneumocystis carinii pneumonia.
AB  - An immunosuppressed rat model was used to determine the pharmacokinetics of
      aerosolized atovaquone (administered with and without a synthetic surfactant) and
      to evaluate the efficacy of inhaled atovaquone in the prevention and treatment of
      Pneumocystis carinii pneumonia (PCP). After a single dose by aerosol, mean peak
      concentrations of atovaquone averaged 52 microg/mL in plasma and 31 microg/g in
      lungs of rats infected with P. carinii. When atovaquone was combined with
      surfactant, mean peak concentrations of 94 microg/mL in plasma and 51 microg/g in
      lung were achieved. Aerosolized synthetic surfactant alone significantly
      increased survival of rats with PCP and, when combined with atovaquone, increased
      plasma and lung concentrations of the drug and eradication of the organism.

PMID- 9534982
TI  - Human immunodeficiency virus type 1 gp160 and gp41 binding to Candida albicans
      selectively enhances candidal virulence in vitro.
AB  - Previously, it has been shown that human immunodeficiency virus (HIV)-1 envelope
      proteins gp160 and gp41 bind to Candida albicans. Whether this interaction
      affects candidal virulence in vitro was investigated. HIV-1 gp160 or gp120
      treatment of C. albicans significantly altered neither growth nor phospholipase
      activity of the fungus. However, treatment of C. albicans with gp160, but not
      with gp120, led to an elevation of free and cell-bound aspartate proteinase. In
      addition, culture supernatants obtained from C. albicans treated with gp160 or
      gp41, but not with gp120, showed a strong increase in proteinase activity.
      Finally, C. albicans viable yeast cells treated with gp160 or gp41 and serum were
      phagocytosed by polymorphonuclear leukocytes to a lesser extent than was C.
      albicans treated with gp120 and serum or serum alone. These findings suggest that
      the interaction between HIV-1 gp160 and C. albicans may promote the virulence of
      C. albicans in HIV-1-positive patients.

PMID- 9534983
TI  - Cerebrospinal fluid levels of biopterin, nitric oxide metabolites, and immune
      activation markers and the clinical course of human cerebral malaria.
AB  - Cerebrospinal fluid samples from 130 children who presented with cerebral malaria
      were investigated to elucidate the impact of biopterin production, NO formation,
      and local immune activation on the clinical course of this disease. Biopterin
      levels were significantly lower in patients who were in a deeper coma (P = .02).
      Cerebrospinal fluid concentrations of NO were significantly higher in children
      who died than in survivors (P = .037); however, this was not the case for
      macrophage activation markers, neopterin, and soluble tumor necrosis factor
      receptor p75 (sTNFR-75). Biopterin, neopterin, and sTNFR-75 but not NO
      concentrations were significantly related to each other. Low biopterin levels in
      deep coma are compatible with an impaired local Th1 response, but the low levels
      could also be due to the scavenging of radicals or to decreased neurotransmitter
      synthesis. Local production of NO, most likely by nonimmune mechanisms, may be
      detrimental in cerebral malaria; however, this appears not to be the case for
      local Th1-mediated immune pathways.

PMID- 9534984
TI  - Evidence of latency and reactivation of both herpes simplex virus (HSV)-1 and HSV
      2 in the genital region.
AB  - While superinfection with different herpes simplex virus (HSV) types has been
      demonstrated in animals, the ability of the two HSV types to colonize and
      reactivate in the same anatomic region in humans has not been well demonstrated.
      In 6 patients, both HSV-1 and HSV-2 was recovered from genital lesions. In 4 of
      them, who initially acquired genital HSV-1 infection, subsequent HSV-2 infection
      presented as a prolonged episode of genital lesions and a marked increase in the
      frequency of genital recurrences. While most of the subsequent clinical
      reactivations were HSV-2, in 2 patients the recurrence rate of genital HSV-1
      increased after the acquisition of HSV-2. These data demonstrate the ability of a
      second HSV type to infect the same anatomic region and illustrate the difference
      in reactivation frequency of the two types in the same person. Typing of HSV
      isolates may be useful in persons with recent alteration in recurrence rates of
      genital HSV.

PMID- 9534985
TI  - Isolation of a second recombinant human respiratory syncytial virus monoclonal
      antibody fragment (Fab RSVF2-5) that exhibits therapeutic efficacy in vivo.
AB  - A second human respiratory syncytial virus (RSV)-neutralizing monoclonal antibody
      was isolated and its binding site was identified. Fab F2-5 is a broadly reactive
      fusion (F) protein-specific recombinant Fab generated by antigen selection from a
      random combinatorial library displayed on the surface of filamentous phage. In an
      in vitro plaque-reduction test, the Fab RSVF2-5 neutralized the infectivity of a
      variety of field isolates representing viruses of both RSV subgroups A and B. The
      Fab recognized an antigenic determinant that differed from the only other human
      anti-F monoclonal antibody (RSV Fab 19) described thus far. A single dose of 4.0
      mg of Fab RSVF2-5/kg of body weight administered by inhalation was sufficient to
      achieve a 2000-fold reduction in pulmonary virus titer in RSV-infected mice. The
      antigen-binding domain of Fab RSVF2-5 offers promise as part of a prophylactic
      regimen for RSV infection in humans.

PMID- 9534986
TI  - Bronchoalveolar interferon-alpha, tumor necrosis factor-alpha, interleukin-1, and
      inflammation during acute influenza in pigs: a possible model for humans?
AB  - Biologically active interferon-alpha, tumor necrosis factor-alpha (TNF-alpha),
      and interleukin-1 (IL-1) were detected in bronchoalveolar lavage (BAL) fluids of
      3-week-old cesarian-derived colostrum-deprived pigs inoculated with H1N1
      influenza virus. Cytokine titers and lung virus titers were significantly higher
      18-24 h after inoculation than at 48-72 h after inoculation in all 4 litters of
      pigs examined. All three cytokines were positively correlated with a 3- to 4-fold
      increase in BAL cell numbers (P < .036) and with a drastic neutrophil
      infiltration (24%-77% of BAL cells vs. 0-1.5% in controls) (P < .001). In
      addition, cytokine production coincided with the onset of general and respiratory
      symptoms of influenza and with the development of a necrotizing bronchopneumonia.
      This study is the first demonstration of TNF-alpha and IL-1 in BAL fluids of a
      natural influenza virus host. It documents that pigs may be a highly valuable
      experimental model in human influenza virus pneumonia.

PMID- 9534987
TI  - Long-lasting remission of cytomegalovirus retinitis without maintenance therapy
      in human immunodeficiency virus-infected patients.
AB  - Seven AIDS patients who were receiving suppressive therapy for previously
      diagnosed cytomegalovirus (CMV) retinitis were offered treatment with protease
      inhibitors (PIs). Secondary prophylaxis for CMV was discontinued after 3 months
      of therapy with PIs if patients had >150 CD4 cells/mm3 and a human
      immunodeficiency virus (HIV) load of <200 copies/mL and if they were negative for
      CMV as determined by qualitative CMV polymerase chain reaction (PCR).
      Ophthalmologic exams were done periodically. After a median follow-up of 9 months
      (range, 9-12), no new episodes of CMV retinitis were observed. CD4 cell counts
      were >150 cells/mm3 in all cases, HIV loads were <200 copies/mL, and results for
      qualitative CMV PCRs remained negative. These observations suggest that for
      selected patients with healed CMV retinitis who have immunologic and virologic
      evidence of a clinical response to potent combination antiretroviral therapy,
      temporary discontinuation of a chronic anti-CMV suppressive therapy may not
      result in further retinal necrosis. However, the long-term immunologic benefit of
      PIs and hence the safety of prolonged withdrawal of anti-CMV therapy is unknown.

PMID- 9534988
TI  - Major expansions of select CD8+ subsets in acute Epstein-Barr virus infection:
      comparison with chronic human immunodeficiency virus disease.
AB  - CD8+ lymphocyte phenotypes were characterized during acute Epstein-Barr virus
      (EBV) infection, and a comparison was made to previous studies of human
      immunodeficiency virus (HIV). This was of interest because CD8+ cells contribute
      to immunologic control of both infections, but the usual outcome of EBV infection
      is benign, whereas untreated HIV infection is fatal. During acute EBV infection,
      CD8+ cells expressed elevated levels of the activation antigens CD38 and HLA-DR,
      similar to that during chronic HIV infection. Within 16 weeks, when EBV latency
      is established, CD8+ cell activation had resolved. In contrast, activation
      persists in HIV infection. Expression of CD38 and HLA-DR on CD8+ cells could be a
      marker for ongoing viral replication in both infections. Other CD8+ cell
      alterations observed in this study of acute EBV infection included increases in
      both CD62L- and CD62L+ CD8+ cells and unique kinetics in the expansion of the
      CD57+CD8+ cell subset.

PMID- 9534989
TI  - Natural history of Epstein-Barr virus infection in a prospective pediatric cohort
      born to human immunodeficiency virus-infected mothers.
AB  - To determine whether Epstein-Barr virus (EBV) constitutes a contributing factor
      in AIDS and, conversely, whether the human immunodeficiency virus (HIV) alters
      the course of primary EBV infection in a pediatric population, 62 children born
      to HIV-infected mothers and prospectively followed were evaluated. EBV infection
      was documented by EBV-specific serology and polymerase chain reaction and by
      clinical history. HIV infection status was determined according to the Centers
      for Disease Control and Prevention pediatric classification system. Demographics
      from HIV-infected and HIV-uninfected children were comparable. The data suggest
      that HIV-infected children may acquire primary EBV infection earlier in life. The
      incidence of accompanying splenomegaly or hepatomegaly (or both) around the time
      of EBV seroconversion was higher among HIV-infected children than among HIV
      uninfected children. In contrast, HIV disease progression and HIV-1 RNA load did
      not seem to be influenced by primary EBV infection.

PMID- 9534990
TI  - Circulating levels of RANTES in human immunodeficiency virus type 1 infection:
      effect of potent antiretroviral therapy.
AB  - RANTES has been found to suppress human immunodeficiency virus type 1 (HIV-1)
      replication. To further elucidate the role of this chemokine in HIV-1 infection,
      RANTES levels were analyzed in serum and platelet-free plasma (PFP) in 53 HIV-1
      infected patients and 20 controls. RANTES levels were significantly elevated in
      both serum and PFP in all clinical stages of HIV-1 infection, with the highest
      levels in CDC groups A and B. In longitudinal testing, the progressors were
      characterized by a pronounced decline in serum levels over time; the
      nonprogressors, however, had only a slight reduction or an increase in RANTES
      levels. During 16 weeks of indinavir therapy, there was an increase in
      circulating RANTES levels and enhanced release of RANTES from stimulated CD8+
      lymphocytes. The decline in RANTES levels along with disease progression is
      compatible with RANTES having a beneficial role in HIV-1-infected patients. The
      increase in RANTES levels during protease inhibitor-containing regimens may
      represent a previously unrecognized immunologic effect of such therapy.

PMID- 9534991
TI  - Intrapartum mucosal exposure to human immunodeficiency virus type 1 (HIV-1) of
      infants born to HIV-1-infected mothers correlates with maternal plasma virus
      burden.
AB  - The majority of vertical infections with human immunodeficiency virus type 1 (HIV
      1) occur at or near delivery, strongly suggesting a mucosal route of
      transmission. The frequency and level of intrapartum mucosal exposure to HIV-1 of
      22 infants born to infected mothers was investigated. Maternal plasma HIV-1 RNA
      and CD4 cell count were measured at delivery. Infant oropharyngeal aspirates
      obtained at birth were examined for HIV-1 RNA by reverse transcription-polymerase
      chain reaction and qualitative nucleic acid sequence-based amplification. Nine
      infants (41%) had detectable levels of HIV-1 RNA, 3 of which were quantifiable
      (mean, 3000 copies/mL). This mucosal exposure to HIV-1 during delivery did not
      lead to infection of any infant. Cesarian delivery did not reduce mucosal
      exposure to HIV-1. Mucosal exposure did not correlate with maternal CD4 cell
      count but did correlate with maternal plasma virus load and was reduced by
      antiretroviral therapy.

PMID- 9534992
TI  - Human immunodeficiency virus type 1 RNA shedding in the female genital tract.
AB  - Cervical and plasma samples obtained twice, at 2-week intervals, from 49 human
      immunodeficiency virus type 1 (HIV-1)-positive women were assayed for HIV-1 RNA.
      More than 100 copies of HIV-1 RNA were detected in cervical swab supernatants
      (CSS) from 24 (49%) of 49 women. HIV-1 RNA in CSS was detected in younger women
      with higher levels of plasma HIV-1 RNA (median, 31,984 vs. 2880 copies/mL; P =
      .0004), lower CD4 cell counts (median, 190 vs. 390 per mm3; P = .012), and lower
      CD4 cell percents (median, 16% vs. 25%; P = .03). In multiple logistic regression
      analysis, only plasma HIV-1 RNA was significantly associated with CSS HIV-1 RNA,
      with an odds ratio of 4.79/log10 increase in plasma HIV-1 RNA (95% confidence
      interval, 1.4-16; P = .01). Detection of HIV-1 RNA in cervical secretions is
      primarily associated with increased plasma HIV-1 RNA.

PMID- 9534993
TI  - Dissemination of Mycobacterium tuberculosis across the San Francisco Bay Area.
AB  - The propensity of Mycobacterium tuberculosis genotypes to spread across
      geographic boundaries was investigated by comparing the IS6110 and polymorphic GC
      rich sequence patterns of M. tuberculosis isolates from San Francisco and the
      East Bay, two distinct regions separated by San Francisco Bay. Of 724 isolates
      from incident tuberculosis patients during 1992 and 1993, only 53 (7.3%) had
      patterns matching > or = 1 isolates from the other region. In the multivariable
      analysis of patient risk factors, an AIDS diagnosis (odds ratio [OR], 1.89; 95%
      confidence interval [CI], 1.00-3.57) and non-Asian race (OR, 3.43; 95% CI, 1.59
      7.42) were associated with having an isolate with a matching pattern. Of 375
      unique IS6110 patterns among San Francisco isolates, only 9 (2.4%) matched
      patterns of East Bay isolates. These population-based data suggest that in the
      San Francisco Bay Area, M. tuberculosis does not rapidly spread across geographic
      boundaries, and tuberculosis control efforts should focus on transmission within
      defined areas.

PMID- 9534994
TI  - Stability of Mycobacterium tuberculosis DNA genotypes.
AB  - To assess genotype stability in Mycobacterium tuberculosis, DNA genotypes were
      compared in sequential isolates from 49 patients who had sputum cultures
      separated by at least 90 days that grew M. tuberculosis. By use of IS6110 and the
      polymorphic GC-rich sequence (PGRS) as markers, it was found that paired isolates
      from 14 (29%) of 49 patients showed changes in their DNA genotypes between
      isolates (12 in IS6110 genotypes and 2 in PGRS genotypes). Changed IS6110
      genotypes were confined to strains with 8-14 bands and were not related to the
      bacterial drug susceptibility, the patients' human immunodeficiency virus
      serostatus, or adherence to therapy. Although this rate of change complicates the
      interpretation of molecular epidemiologic studies, it can be exploited to gain
      additional insight into disease transmission. Furthermore, IS6110-related
      mutations may be a major source of genetic plasticity in M. tuberculosis and
      provide insights into the organism's evolution and virulence.

PMID- 9534995
TI  - Antibody avidity as a surrogate marker of successful priming by Haemophilus
      influenzae type b conjugate vaccines following infant immunization.
AB  - Evaluation of the new generation of conjugate vaccines is hampered by the absence
      of reliable surrogate markers of immunologic memory. Memory responses are
      characterized by rapid production of relatively high-avidity antibody; thus, a
      solid-phase ELISA was adapted for the measurement of anti-Haemophilus influenzae
      type b (Hib) IgG avidity. In a cohort of infants vaccinated at 2, 3, and 4 months
      of age with Hib conjugate vaccines, avidity increased in the period following
      vaccination, while antibody titer fell. After a booster dose at 1 year of age,
      both antibody titer and avidity increased. In a cohort with anti-Hib IgG <1.0
      microg/mL following primary immunization, antibody avidity after booster was low,
      indicating an absence of priming. Antibody avidity may help distinguish, in
      persons with low antibody titers, between those who are primed for memory and
      those who are not.

PMID- 9534996
TI  - Identification of a highly encapsulated, genetically related group of invasive
      type III group B streptococci.
AB  - Type III group B streptococci (GBS) isolated from Tokyo and Salt Lake City were
      classified according to the similarity of HindIII and Sse83871 restriction digest
      patterns (RDPs) of bacterial DNA. The bacteria were clustered into three RDP
      types, with excellent correlation between subtyping based on the two enzymes. The
      majority (91%) of invasive isolates obtained from neonates were RDP type III-3.
      The mean sialic acid content of the III-3 strains was higher than that of other
      type III strains. Closely related isolates were concordant for expression of the
      bacterial enzyme C5a-ase, but invasive strains were no more likely to be C5a-ase
      positive than were strains isolated from the genitourinary tract of pregnant
      women. These data indicate that a group of genetically related organisms with
      increased capsule production causes the majority of invasive type III GBS
      disease.

PMID- 9534997
TI  - Colonization with and acquisition of uropathogenic Escherichia coli as revealed
      by polymerase chain reaction-based detection.
AB  - The prevalence of colonization with uropathogenic Escherichia coli and their
      reservoirs and routes of acquisition are incompletely defined. To help clarify
      these issues, polymerase chain reaction (PCR)-based strain typing assays were
      used to evaluate the fecal and vaginal E. coli flora of 11 volunteers. PCR
      detected the virulence genes papG, aer, and cnf significantly more frequently in
      mixed intestinal samples than in the corresponding predominant strains, evidence
      that traditional methods are suboptimal for detecting colonization with
      uropathogens. For strain typing, repetitive-element PCR was as discriminating as
      pulsed-field gel electrophoresis and O:H serotyping but more convenient.
      Molecular epidemiologic analysis of subjects' E. coli suggested emergence of
      occult uropathogenic strains from within the host's own intestinal flora, strain
      sharing between household members, and de novo acquisition of (unshared)
      uropathogenic strains. These methods should facilitate the studies needed to
      clarify the relative contributions of these three pathways to the pathogenesis of
      urinary tract infection.

PMID- 9534998
TI  - The individual and joint contributions of Helicobacter pylori infection and
      family history to the risk for peptic ulcer disease.
AB  - Family history of peptic ulcer and infection with Helicobacter pylori have been
      identified as major risk factors for peptic ulcer disease. It is unclear,
      however, to what degree their impacts are independent of each other. This
      question was addressed in a cross-sectional study among 299 consecutive out
      patients (25-54 years old) of a general practitioner. Adjusted odds ratios (95%
      confidence intervals) for gastroscopically verified peptic ulcer disease were 3.8
      (1.4-10.1) for persons with H. pylori infection, 8.4 (2.9-24.1) for persons with
      a family history of ulcer, and 29.5 (6.1-143.9) for persons with both risk
      factors compared with persons without these risk factors. These results suggest
      strong, multiplicative contributions of both factors to the risk for peptic ulcer
      disease.

PMID- 9534999
TI  - Selection and characterization of Toxoplasma gondii mutants resistant to
      artemisinin.
AB  - Toxoplasma gondii infection, like malaria, is sensitive to inhibition by
      artemisinin (ART). Mechanisms of action for ART in malaria treatment have been
      proposed, but little is known about its effects in T. gondii infection. To better
      understand its inhibitory effects on T. gondii, mutants resistant to ART were
      selected by progressive culture in permissive levels of the drug. Five clonal
      isolates were established and characterized. The isolates were approximately 65
      fold less sensitive to ART than is the parental RH and showed cross-resistance to
      the ART derivatives dihydroartemisinin and artemether. In addition to ART
      resistance, 1 clone (C9) formed morphologically unusual parasitophorous vacuoles
      and another (A2) was avirulent for mice and protected mice from challenge with
      the wild type. These clonal T. gondii mutant isolates will be useful for the
      study of not only the mechanism of action of ART but also parasite vacuole
      biology and virulence factors.

PMID- 9535000
TI  - Persistence of humoral response against sporozoite and blood-stage malaria
      antigens 7 years after a brief exposure to Plasmodium vivax.
AB  - The persistence of malarial antibodies was evaluated in subjects living in a
      rural community (in Minas Gerais State, Brazil) briefly exposed to a Plasmodium
      vivax malaria outbreak outside of the area in which malaria was endemic.
      Transmission was interrupted by treatment of all patients and their relatives
      and/or neighbors, although the latter had neither symptoms nor blood parasites.
      Antibodies to P. vivax antigens (recombinant proteins from sporozoites [rPvCS]
      and from blood stages [rPv200]) were measured in parallel by ELISA with sera
      collected at two time points after transmission. Anti-rPvCS IgG antibodies were
      positive in approximately 40% and 20% of the subjects 8 months and 7 years after
      exposure, respectively. Anti-rPv200 IgG was first detected in 61% of the subjects
      who had had malarial symptoms and remained positive in 47% after 7 years. Among
      the prophylactically treated group, anti-rPv200 IgG was detected in only 28%
      after 8 months. The levels of both antibodies decreased with time in all positive
      subjects.

PMID- 9535001
TI  - Human herpesvirus 8 group B and C variants circulating in Sao Paulo, Brazil.

PMID- 9535002
TI  - Drug-susceptible tuberculosis.

PMID- 9535003
TI  - Follow-up study of verocytotoxigenic Escherichia coli infection in dairy farm
      families.

PMID- 9535004
TI  - Direct effects of diazoxide on mitochondria in pancreatic B-cells and on isolated
      liver mitochondria.
AB  - 1. The direct effects of diazoxide on mitochondrial membrane potential, Ca2+
      transport, oxygen consumption and ATP generation were investigated in mouse
      pancreatic B-cells and rat liver mitochondria. 2. Diazoxide, at concentrations
      commonly used to open adenosine 5'-triphosphate (ATP)-dependent K+-channels
      (K(ATP) channels) in pancreatic B-cells (100 to 1000 microM), decreased
      mitochondrial membrane potential in mouse intact perifused B-cells, as evidenced
      by an increase of rhodamine 123 fluorescence. This reversible decrease of
      membrane potential occurred at non-stimulating (5 mM) and stimulating (20 mM)
      glucose concentrations. 3. A decrease of mitochondrial membrane potential in
      perifused B-cells was also caused by pinacidil, but no effect could be seen with
      levcromakalim (500 microM each). 4. Measurements by a tetraphenylphosphonium
      sensitive electrode of the membrane potential of rat isolated liver mitochondria
      confirmed that diazoxide decreased mitochondrial membrane potential by a direct
      action. Pretreatment with glibenclamide (2 microM) did not antagonize the effects
      of diazoxide. 5. In Fura 2-loaded B-cells perifused with the Ca2+ channel
      blocker, D 600, a moderate, reversible increase of intracellular Ca2+
      concentration could be seen in response to 500 microM diazoxide. This
      intracellular Ca2+ mobilization may be due to mitochondrial Ca2+ release, since
      the reduction of membrane potential of isolated liver mitochondria by diazoxide
      was accompanied by an accelerated release of Ca2+ stored in the mitochondria. 6.
      In the presence of 500 microM diazoxide, ATP content of pancreatic islets
      incubated in 20 mM glucose for 30 min was significantly decreased by 29%.
      However, insulin secretion from mouse perifused islets induced by 40 mM K+ in the
      presence of 10 mM glucose was not inhibited by 500 microM diazoxide, suggesting
      that the energy-dependent processes of insulin secretion distal to Ca2+ influx
      were not affected by diazoxide at this concentration. 7. The effects of diazoxide
      on oxygen consumption and ATP production of liver mitochondria varied depending
      on the respiratory substrates (5 mM succinate, 10 mM alpha-ketoisocaproic acid, 2
      mM tetramethyl phenylenediamine plus 5 mM ascorbic acid), indicating an
      inhibition of respiratory chain complex II. Pinacidil, but not levcromakalim,
      inhibited alpha-ketoisocaproic acid-fuelled ATP production. 8. In conclusion,
      diazoxide directly affects mitochondrial energy metabolism, which may be of
      relevance for stimulus-secretion coupling in pancreatic B-cells.

PMID- 9535005
TI  - Distribution of P2Y receptor subtypes on haematopoietic cells.
AB  - 1. RT-PCR-southern hybridization analyses with radiolabelled P2Y receptor cDNAs
      as probes indicated that the peripheral blood leukocytes and the human umbilical
      vein endothelial cells express P2Y1, P2Y2, P2Y4 and P2Y6 receptors. 2. Of the
      haematopoietic cell lines tested, promonocytic U937 cells express P2Y2 and P2Y6,
      but not P2Y1 or P2Y4; promyelocytic HL-60 cells express the P2Y1, P2Y2 and P2Y6
      receptors but not the P2Y4 receptor; K562 cells express P2Y1 but not P2Y2, P2Y4
      or P2Y6; and Dami cells express P2Y1, P2Y2, P2Y4 and P2Y6 receptors. 3. Of the
      peripheral blood leukocytes tested, polymorphonuclear cells express P2Y4 and P2Y6
      but not P2Y1 or P2Y2 receptors; monocytes express P2Y1, P2Y2, P2Y4 and P2Y6
      receptors and lymphocytes express P2Y1, P2Y2, P2Y4 and P2Y6 receptors. 4. These
      results suggest a physiological role for different P2Y receptor subtypes in the
      extracellular nucleotide-mediated stimulation of monocytes, neutrophils,
      lymphocytes and endothelial cells.

PMID- 9535006
TI  - Effects of inhibition of prostaglandin endoperoxide synthase-2 in chronic gastro
      intestinal ulcer models in rats.
AB  - 1. In the stomach, prostaglandins protect the gastric mucosa against injuries.
      One rate-limiting step in prostaglandin synthesis is mediated by prostaglandin
      endoperoxide synthase (PGHS), the target enzyme of non-steroidal anti
      inflammatory drugs (NSAIDs). Two isoforms of PGHS exist: a constitutive (PGHS-1)
      and an inducible (PGHS-2) enzyme. PGHS-1 is the major source of gastric
      prostaglandins under physiological conditions. Inhibition of prostaglandin
      synthesis by traditional NSAIDs such as indomethacin and diclofenac which non
      selectively inhibit both PGHS-1 and PGHS-2, causes gastric and intestinal
      ulceration and delays gastric ulcer healing in chronic models. It has been shown
      that selective PGHS-2 inhibitors such as L-745,337 (5-methanesulphonamide-6-(2,4
      difluorothio-phenyl)-1-inda none) are not ulcerogenic and do not inhibit gastro
      intestinal prostaglandin synthesis. However, minimal information is available on
      the long-term effects of PGHS-2 inhibitors on the healing of previously
      established gastric injuries. We assessed the cellular localization and
      expression of PGHS-1 and PGHS-2 during gastric ulcer healing and assessed the
      effects of L-745,337 on previously established cryoulcers in the rat gastric
      stomach. 2. PGHS-1 and PGHS-2 were located and quantified by immunohistochemistry
      during experimental gastric ulcer healing. PGHS-2 immunoreactivity was only
      negligible in the normal gastric wall, but after gastric ulcerations, it was
      strongly detected in monocytes, macrophages, fibroblasts and endothelial cells
      below and between the regenerative glands. PGHS-1 immunoreactivity detected in
      normal gastric mucosa, disappeared after gastric ulceration in the mucosa
      adjacent to the ulcer crater. However, it reappeared in the regenerative glands
      from day 5 onwards. Thus, PGHS-1 and PGHS-2 were located at different sites and
      their maximal expression followed a different time-sequence. 3. We assessed the
      effects of L-745,337, indomethacin and diclofenac on gastric ulcer healing and
      histological healing parameters in rats. L-745,337, indomethacin and diclofenac
      dose-dependently decreased the healing of gastric ulcers. L-745,337, indomethacin
      and diclofenac decreased epithelial cell proliferation in the ulcer margin and
      microvessel density in the ulcer bed on day 8 and increased the thickness of the
      granulation tissue below the ulcer crater and the gap between both edges of the
      muscularis mucosae on day 15. Indomethacin and diclofenac, but not L-745,337,
      decreased synthesis of 6-keto-PGF1alpha and PGE2 in tissue fragments from the
      stomach and terminal ileum and decreased platelet thromboxane B2 synthesis in
      clotting whole blood. 4. Dose-response curves for the inhibition of chronic
      gastric ulcer healing by L-745,337 (administered twice daily intragastrically)
      showed an ID50 value of 1.7 mg (4.3 micromol) kg(-1). Dose-response curves for
      the inhibition of PGE2 synthesis in inflammatory exudates in the acute
      carrageenin sponge rat model, showed ID50 values of 1.1 mg (3.1 micromol) kg(-1)
      and 1.3 (3.3 micromol) mg kg(-1) for indomethacin and L-745,337, respectively.
      Thus, inhibition of chronic gastric ulcer healing by L-745,337 occurs within a
      potentially therapeutic dose-range. 5. In summary, PGHS-2 is markedly accumulated
      after gastric ulceration in monocytes, macrophages, fibroblasts and endothelial
      cells in regions of maximal repair activity. Selective inhibition of PGHS-2 by L
      745,337 delayed gastric ulcer healing though interference with epithelial cell
      proliferation, angiogenesis and maturation of granulation tissue in a potentially
      therapeutic dose range. PGHS-2-derived prostaglandins seem to have an important
      role in gastric ulcer healing.

PMID- 9535007
TI  - Effects of Ca2+ channel antagonists on striatal dopamine and DOPA release,
      studied by in vivo microdialysis.
AB  - 1. To elucidate the mechanisms regulating the release of striatal dopamine and
      its precursor, 3,4-dihydroxyphenylalanine (DOPA), we determined the effects of
      various Ca2+ channel antagonists, an N-type Ca2+ channel antagonist, omega
      conotoxin GVIA, a P-type Ca2+ channel antagonist, omega-agatoxin IVA, and a Q
      type Ca2+ channel antagonist, omega-conotoxin MVIIC, on the basal and Ca2+- and
      K+-evoked release of striatal dopamine and DOPA, by use of in vivo microdialysis.
      2. Omega-conotoxin GVIA strongly inhibited striatal basal dopamine release (IC50
      = 0.48 nM), whereas this toxin only weakly modulated basal striatal DOPA release
      (IC50 = 9.55 nM). Neither omega-agatoxin IVA nor omega-conotoxin MVIIC affected
      the basal striatal release of dopamine and DOPA. 3. Omega-conotoxin GVIA strongly
      inhibited Ca2+-evoked striatal dopamine release (IC50 = 0.40 nM), whereas Ca2+
      evoked striatal DOPA release only was weakly modulated (IC50 = 10.51 nM). Neither
      omega-agatoxin IVA nor omega-conotoxin MVIIC affected the Ca2+-evoked release of
      striatal dopamine and DOPA. 4. Both omega-agatoxin IVA and omega-conotoxin MVIIC
      inhibited the K+-evoked release of striatal dopamine (IC50 of omega-agatoxin IVA
      = 2.65 nM; IC50 of omega-conotoxin MVIIC = 12.54 nM) and DOPA (IC50 of omega
      agatoxin IVA = 0.15 nM; IC50 of omega-conotoxin MVIIC = 3.05 nM), whereas omega
      conotoxin GVIA had no effect on the K+-evoked release of striatal dopamine and
      DOPA. 5. An increase in the extracellular Ca2+ and K+ concentrations (Ca2+- and
      K+-evoked stimulation) did not affect tyrosine hydroxylase activity in vivo. 6.
      These findings suggest that striatal DOPA release is neurotransmitter-like and
      that, unlike the mechanisms of striatal dopaminergic transmission, this striatal
      DOPA transmission is at least partly regulated by voltage-sensitive Ca2+
      channels.

PMID- 9535008
TI  - Emodin-induced muscle contraction of mouse diaphragm and the involvement of Ca2+
      influx and Ca2+ release from sarcoplasmic reticulum.
AB  - 1. The effects on skeletal muscle of emodin, an anthraquinone, were studied in
      the mouse isolated diaphragm and sarcoplasmic reticulum (SR) membrane vesicles.
      2. Emodin dose-dependently caused muscle contracture, simultaneously depressing
      twitch amplitude. Neither tubocurarine nor tetrodotoxin blocked the contraction
      suggesting that it was caused myogenically. 3. The contraction induced by emodin
      persisted in a Ca2+ free medium with a slight reduction in the maximal force of
      contraction. The contraction induced by emodin in the Ca2+ free medium was
      completely blocked when the internal Ca2+ pool of the muscle was depleted by
      ryanodine. These data suggest that the contraction caused by emodin is due to the
      release of Ca2+ from the intracellular ryanodine-sensitive pool. 4. In contrast
      to the effect seen in the Ca2+ free medium, emodin induced a small but consisted
      contraction in the ryanodine-treated muscle in Krebs medium. The contraction was
      blocked in the presence of dithiothreitol and was partially blocked by
      nifedipine, suggesting that oxidation of a sulphhydryl group on the external site
      of dihydropyridine receptor is involved. 5. Emodin dose-dependently increased
      Ca2+ release from actively loaded SR vesicles and this effect was blocked by
      ruthenium red, a specific Ca2+ release channel blocker, and the thiol reducing
      agent, DTT, suggesting that emodin induced Ca2+ release through oxidation of the
      critical SH of the ryanodine receptor. 6. [3H]-ryanodine binding was dose
      dependently potentiated by emodin in a biphasic manner. The degree of
      potentiation of ryanodine binding by emodin increased dose-dependently at
      concentrations up to 10 microM but decreased at higher concentrations of 10-100
      microM. 7. These data suggest that muscle contraction induced by emodin is due to
      Ca2+ release from the SR of skeletal muscle, as a result of oxidation of the
      ryanodine receptor and influx of extracellular Ca2+ through voltage-dependent
      Ca2+ channels of the plasma membrane.

PMID- 9535009
TI  - Roles of calcium-activated and voltage-gated delayed rectifier potassium channels
      in endothelium-dependent vasorelaxation of the rabbit middle cerebral artery.
AB  - 1. The cellular mechanism(s) of action of endothelium-derived vasodilator
      substances in the rabbit middle cerebral artery (RMCA) were investigated.
      Specifically, the subtypes of potassium channels involved in the effects of
      endothelium-derived relaxing factors (EDRFs) in acetylcholine (ACh)-induced
      endothelium-dependent vasorelaxation in this vessel were systematically compared.
      2. In the endothelium-intact RMCA precontracted with histamine (3 microM), ACh
      induced a concentration-dependent vasorelaxation, which was sensitive to
      indomethacin (10 microM) or N(G)-nitro-L-arginine (L-NOARG; 100 microM); pD2
      values 8.36 vs 7.40 and 6.38, P < 0.01 for both, n = 6 and abolished by a
      combination of both agents. ACh caused relaxation in the presence of high K+ PSS
      (40 mM KCl), which was not affected by indomethacin, but abolished by L-NOARG and
      a combination of indomethacin and L-NOARG. 3. In the presence of indomethacin,
      relaxation to ACh in the endothelium-intact RMCA precontracted with histamine was
      unaffected by either glibenclamide (10 microM), an ATP-sensitive K+ channel
      (K[ATP]) blocker, 4-aminopyridine (4-AP, 1 mM) or dendrotoxin (DTX, 0.1 microM),
      delayed rectifier K channel (Kv) blockers. However, relaxation responses to ACh
      were significantly inhibited by either LY83583 (10 microM) and 1H
      [1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ, 10 microM), guanylyl cyclase
      inhibitors, or charybdotoxin (CTX; 0.1 microM), iberiotoxin (ITX, 0.1 microM) and
      apamin (APA, 0.1 microM), large conductance Ca2+-activated K+ channels (BK[Ca])
      blocker and small conductance Ca2+-activated K+ channel (SK[Ca]) blocker,
      respectively. 4. In the presence of L-NOARG, relaxation to ACh was unaffected by
      glibenclamide or the cytochrome P450 mono-oxygenase inhibitor, clotrimazole (1
      microM), but was significantly inhibited by either 9-(tetrahydro-2-furanyl)-9H
      purin-6-amine (SQ 22,536, 10 microM) and 2',3'-dideoxyadenosine (2',3'-DDA, 30
      microM), adenylyl cyclase inhibitors, or 4-AP, DTX, CTX, ITX and APA. 5. In the
      endothelium-denuded RMCA precontracted with histamine, authentic NO-induced
      relaxation was unaffected by glibenclamide, 4-AP and DTX, but significantly
      reduced by ODQ, ITX and APA. Authentic prostaglandin I2 (PGI2)-induced relaxation
      was unaffected by glibenclamide, but significantly reduced by 2',3'-DDA, 4-AP,
      DTX, ITX and APA. Forskolin-induced relaxation was significantly inhibited by
      high K+, CTX and 4-AP. 6. These results indicate that: (1) in the RMCA the EDRFs
      released by ACh are NO and a prostanoid (presumably PGI2), and there is no
      evidence for the release of a non-NO/PGI2 endothelium-derived hyperpolarizing
      factor (EDHF), (2) K(Ca) channels are involved in NO-mediated relaxation of the
      RMCA but both K(Ca) and Kv channels are involved in PGI2-mediated relaxation.

PMID- 9535010
TI  - The effect of prolonged treatment with imipramine on the biosynthesis and
      functional characteristics of D2 dopamine receptors in the rat caudate putamen.
AB  - 1. The present study shows the effects of imipramine in a single dose (10 mg kg(
      1), p.o.) or following repeated (14 days, twice a day) treatment on the level of
      mRNA coding for D2 dopamine receptors in the rat caudate putamen (CP). Repeated
      administration of imipramine resulted in the increase of the level of mRNA coding
      for D2 dopamine receptors. 2. Radioligand binding studies with the D2 receptor
      agonist, [3H]-N-0437, indicated, that following imipramine administration, the
      affinity of the agonist for the D2 dopamine receptor significantly increased,
      though without any alterations in the Bmax. 3. Pharmacological manipulations (by
      use of forskolin, GppNHp and quinpirole) of the cyclic AMP generating system, ex
      vivo following administration of imipramine indicated that an up-regulation of
      factors inhibiting cyclic GMP formation takes place. 4. Most probably it is the
      D2 dopamine receptor which undergoes functional up-regulation, resulting from the
      enhancement of its biosynthesis.

PMID- 9535011
TI  - Role of nitric oxide in regulation of gastric acid secretion in rats: effects of
      NO donors and NO synthase inhibitor.
AB  - 1. The role of nitric oxide (NO) in the regulation of acid secretion was examined
      in the anaesthetized rat. 2. A rat stomach was mounted in an ex vivo chamber,
      instilled with 2 ml of saline every 15 min, and the recovered sample was titrated
      at pH 7.0 against 0.1 N NaOH by use of an automatic titrator for acid secretion.
      Gastric mucosal blood flow (GMBF) was measured simultaneously by laser Doppler
      flowmeter. 3. Intragastric application of NO donors such as FK409 (3 and 6 mg ml[
      1]) and sodium nitroprusside (SNP; 6 and 12 mg ml[-1]) as well as i.p.
      administration of cimetidine (60 mg kg[-1]), a histamine H2-receptor antagonist,
      significantly inhibited the increase in acid secretion in response to
      pentagastrin (60 microg kg(-1) h(-1), i.v.), in doses that increased gastric
      mucosal blood flow (GMBF). 4. Intragastric application of FK409 (6 mg ml[-1])
      increased both basal and stimulated acid secretion induced by YM-14673 (0.3 mg
      kg(-1), i.v.), an analogue of thyrotropin-releasing hormone (TRH), but had no
      effect on the acid secretory response induced by histamine (4 mg kg(-1) h(-1),
      i.v.). 5. Pretreatment with N(G)-nitro-L-arginine methyl ester (L-NAME; 10 mg kg(
      1), i.v.) did not affect basal acid secretion, but significantly potentiated the
      increase in acid secretion induced by YM-14673 and slightly augmented the acid
      secretory response to pentagastrin. 6. Both pentagastrin and YM-14673 increased
      the release of nitrite plus nitrate (NOx), stable NO metabolites, into the
      gastric lumen, and these changes were completely inhibited by prior
      administration of L-NAME (10 mg kg(-1), i.v.). 7. Pentagastrin caused an increase
      in luminal release of histamine and this response was significantly suppressed by
      intragastric application of FK409 (6 mg ml[-1]). 8. These results suggest that
      either exogenous or endogenous NO has an inhibitory action on gastric acid
      secretion through suppression of histamine release from enterochromaffin-like
      (ECL) cells.

PMID- 9535012
TI  - Role of K+ channel opening and stimulation of cyclic GMP in the vasorelaxant
      effects of nicorandil in isolated piglet pulmonary and mesenteric arteries:
      relative efficacy and interactions between both pathways.
AB  - 1. The effects of the K+ channel opener levcromakalim, the guanylate cyclase
      stimulant nitroprusside and the dual drug nicorandil (K+ channel opener and
      guanylate cyclase stimulant) were analysed in piglet isolated endothelium-denuded
      pulmonary (PA) and mesenteric (MA) arteries stimulated by noradrenaline (NA) or
      by the thromboxane A2 mimetic U46619. 2. Nicorandil, levcromakalim and verapamil
      were less potent in PA than in MA, the efficacy of levcromakalim was also reduced
      in PA. The effects of nicorandil and levcromakalim were similar in arteries pre
      contracted by NA and U46619, whereas verapamil was more potent in arteries pre
      contracted by NA. Nitroprusside was equipotent in MA pre-contracted by either NA
      or U46619 and in PA pre-contracted by NA whereas in PA pre-contracted by U46619,
      nitroprusside showed lower potency and efficacy. 3. The relaxant effects of
      levcromakalim and nitroprusside were inhibited by 10(-5) M glibenclamide and 10(
      6) M ODQ, respectively. Nicorandil-induced relaxation was inhibited by ODQ in all
      experimental conditions, whereas glibenclamide had inhibitory effects in PA and
      MA pre-contracted by U46619, had no effect in PA pre-contracted by NA and in MA
      pre-contracted by NA it was only inhibitory in the presence of ODQ. 4. No
      apparent interactions were found between nitroprusside and levcromakalim as
      indicated by the lack of effects of pretreatment with one of them (producing 20
      35% relaxation) on the potency of the relaxant response to the other. However, in
      PA pre-contracted by U46619, where nitroprusside or levcromakalim induced only
      partial relaxation, the combination of both mechanisms (either by combining
      nitroprusside plus levcromakalim or by nicorandil) was able to induce full
      vasodilatation. 5. In conclusion, K+ channel opening and guanylate cyclase
      stimulation are independent pathways that induce additive vasorelaxation in
      piglet PA and MA. The mechanism of action of nicorandil is dependent on the
      artery and on the nature of the agonist employed to precontract the artery. The
      relative efficacy of K+ channel opening vs guanylate cyclase stimulation may
      partially explain the preferential contribution of each mechanism to the relaxant
      effects of nicorandil.

PMID- 9535013
TI  - Effect of gamma-mangostin through the inhibition of 5-hydroxy-tryptamine2A
      receptors in 5-fluoro-alpha-methyltryptamine-induced head-twitch responses of
      mice.
AB  - 1. Intracerebronventricular (i.c.v.) injection of gamma-mangostin (10-40
      nmol/mouse), a major compound of the fruit hull of Garcinia mangostana Lin., like
      ketanserin (10, 20 nmol/mouse, i.c.v.) inhibited 5-fluoro-alpha-methyltryptamine
      (5-FMT) (45 mg kg(-1), i.p.)-induced head-twitch response in mice in the presence
      or absence of citalopram (a 5-hydroxytryptamine (5-HT)-uptake inhibitor). 2.
      Neither the 5-FMT- nor the 8-hydroxy-2-(di-n-propylamino)tetralin (5-HT1A
      agonist)-induced 5-HT syndrome (head weaving and hindlimb abduction) was affected
      by gamma-mangostin or ketanserin. 3. The locomotor activity stimulated by 5-FMT
      through the activation of alpha1-adrenoceptors did not alter in the presence of
      gamma-mangostin. 4. 5-HT-induced inositol phosphates accumulation in mouse brain
      slices was abolished by ketanserin. Gamma-mangostin caused a concentration
      dependent inhibition of the inositol phosphates accumulation. 5. Gamma-mangostin
      caused a concentration-dependent inhibition of the binding of [3H]-spiperone, a
      specific 5-HT2A receptor antagonist, to mouse brain membranes. 6. Kinetic
      analysis of the [3H]-spiperone binding revealed that gamma-mangostin increased
      the Kd value without affecting the Bmax value, indicating the mode of the
      competitive nature of the inhibition by gamma-mangostin. 7. These results suggest
      that gamma-mangostin inhibits 5-FMT-induced head-twitch response in mice by
      blocking 5-HT2A receptors not by blocking the release of 5-HT from the central
      neurone. Gamma-mangostin is a promising 5-HT2A receptor antagonist in the central
      nervous system.

PMID- 9535014
TI  - CGRP and nitric oxide of neuronal origin and their involvement in neurogenic
      vasodilatation in rat skin microvasculature.
AB  - 1. Sensory nerves are important for the initiation of neurogenic inflammation and
      tissue repair. Both calcitonin gene-related peptide (CGRP) and nitric oxide (NO)
      have been implicated in neurogenic vasodilatation and inflammatory responses. 2.
      A blister model in the rat hind footpad was used as a site to induce neurogenic
      vasodilatation in response to antidromic electrical stimulation of the sciatic
      nerve. Blood flux was monitored with a laser Doppler flow monitor. 3. The
      quantitative contributions of CGRP and NO to vasodilatation were examined by use
      of the CGRP receptor antagonist CGRP8-37 and NO synthase inhibitors 7
      nitroindazole (7-NI), 3-bromo 7-NI and N(G)-nitro L-arginine methyl ester (L
      NAME). The potential modulatory role of endothelin was examined by use of the
      ET(A) receptor antagonist BQ-123. 4. CGRP8-37 (10 microM) was perfused over the
      blister base before nerve stimulation and continuously throughout the post
      stimulation period, resulting in a significant reduction (41%) in the blood flux
      vascular response. 5. Pretreatment with the specific neuronal NO synthase
      inhibitors, 7-NI and 3-bromo 7-NI (10 mg kg(-1), i.v.), and of the non-specific L
      NAME (100 microM), resulted in significant inhibition of the blood flux response
      (36%, 72% and 57% decrease, respectively). In contrast, 7-NI treatment in young
      rats pretreated with capsaicin had no further effect on the vascular response,
      suggesting that the source of NO is the sensory nerves. 6. BQ-123 (10 microM)
      significantly enhanced the stimulation-induced blood flux response (61%
      increase). When 7-NI was co-administered with either CGRP8-37 or BQ-123, the drug
      actions were additive, suggesting that there was no interaction between NO and
      CGRP or endothelin. 7. These data suggest that both NO and CGRP participate in
      neurogenic vasodilatation in rat skin microvasculature and that this response is
      modulated by endogenous endothelin.

PMID- 9535015
TI  - Effect of cilostazol, a phosphodiesterase type III inhibitor, on histamine
      induced increase in [Ca2+]i and force in middle cerebral artery of the rabbit.
AB  - 1. The effect of cilostazol, an inhibitor of phosphodiesterase type III (PDE
      III), on the contraction induced by histamine was studied by making simultaneous
      measurements of isometric force and the intracellular concentration of Ca2+
      ([Ca2+]i) in endothelium-denuded muscle strips from the peripheral part of the
      middle cerebral artery of the rabbit. 2. High K+ (80 mM) produced a phasic,
      followed by a tonic increase in both [Ca2+]i and force. Cilostazol (10 microM)
      did not modify the resting [Ca2+]i, but it did significantly decrease the tonic
      contraction induced by high K+ without a corresponding change in the [Ca2+]i
      response. 3. Histamine (3 microM) produced a phasic, followed by a tonic increase
      in both [Ca2+]i and force. Cilostazol (3 and 10 microM) significantly reduced
      both the phasic and tonic increases in [Ca2+]i and force induced by histamine, in
      a concentration-dependent manner. 4. Rp-adenosine-3':5'-cyclic
      monophosphorothioate (Rp-cAMPS, 0.1 mM), a PDE-resistant inhibitor of protein
      kinase A (and as such a cyclic AMP antagonist), did not modify the increases in
      [Ca2+]i and force induced by histamine alone, but it did significantly decrease
      the cilostazol-induced inhibition of the histamine-induced responses. 5. In Ca2+
      free solution containing 2 mM EGTA, both histamine (3 microM) and caffeine (10
      mM) transiently increased [Ca2+]i and force. Cilostazol (1-10 microM) (i)
      significantly reduced the increases in [Ca2+]i and force induced by histamine,
      and (ii) significantly reduced the increase in force but not the increase in
      [Ca2+]i induced by caffeine. 6. In ryanodine-treated strips, which had
      functionally lost the histamine-sensitive Ca2+ storage sites, histamine (3
      microM) slowly increased [Ca2+]i and force. Cilostazol (3 and 10 microM) lowered
      the resting [Ca2+]i, but did not modify the histamine-induced increase in
      [Ca2+]i, suggesting that functional Ca2+ storage sites are required for the
      cilostazol-induced inhibition of histamine-induced Ca2+ mobilization. 7. The
      [Ca2+]i-force relationship was obtained in ryanodine-treated strips by applying
      ascending concentrations of Ca2+ (0.16-2.6 mM) in Ca2+-free solution containing
      100 mM K+. Histamine (3 microM) shifted the [Ca2+]i-force relationship to the
      left and increased the maximum Ca2+-induced force. Under the same conditions,
      whether in the presence or absence of 3 microM histamine, cilostazol (3-10
      microM) shifted the [Ca2+]i-force relationship to the right without producing a
      change in the maximum Ca2+-induced force. 8. It is concluded that, in smooth
      muscle of the peripheral part of the rabbit middle cerebral artery, cilostazol
      attenuates the histamine-induced contraction both by inhibiting histamine-induced
      Ca2+ mobilization and by reducing the myofilament Ca2+ sensitivity. It is
      suggested that the increase in the cellular concentration of cyclic AMP that will
      follow the inhibition of PDE III may play an important role in the cilostazol
      induced inhibition of the histamine-contraction.

PMID- 9535017
TI  - Stimulation of nitric oxide release from rat spinal cord by prostaglandin E2.
AB  - 1. We recently demonstrated that intrathecal administration of prostaglandin E2
      (PGE2) and PGF2alpha induced allodynia through a pathway that includes the
      glutamate receptor and nitric oxide (NO)-generating systems from pharmacological
      studies. In order to clarify the involvement of NO in prostaglandin-induced
      allodynia, we measured NO released from rat spinal cord slices by a
      chemiluminescence method. 2. PGE2 stimulated NO release from both dorsal and
      ventral regions all along the spinal cord. PGE2 stimulated the release within 10
      min and increased it in a time-dependent manner. 3. The PGE2-induced NO release
      was observed at 100 nM-10 microM. PGF2alpha stimulated the release at
      concentrations higher than 1 microM, but PGD2 (up to 10 microM) did not enhance
      it. 4. 17-Phenyl-omega-trinor PGE2 (EP1 > EP3) and sulprostone (EP1 < EP3) were
      as potent as PGE2, but PGE1 was less potent, in stimulating NO release. While M&B
      28767 (EP3) did not enhance the release, butaprost (EP2) stimulated it at 1
      microM. The PGE2-evoked release was blocked by ONO-NT-012, a bifunctional EP1
      antagonist/EP3 agonist. 5. The PGE2-evoked release was Ca2+-dependent and blocked
      by MK-801 (NMDA receptor antagonist) and L-NAME (NO synthase inhibitor). The
      release was also inhibited by PGD2 and dibutyryl-cyclic AMP. 6. The present study
      demonstrated that PGE2 stimulates NO release in the rat spinal cord by activation
      of NMDA receptors through the EP1 receptor, and supports our previous findings
      that the NO-generating system is involved in the PGE2-induced allodynia.

PMID- 9535016
TI  - Suppression of nitric oxide formation by tyrosine kinase inhibitors in murine N9
      microglia.
AB  - 1. Microglial cells represent the first line of defence in the brain against
      infection and damage. However, under conditions of chronic inflammation and
      neurodegeneration, excessive activation of microglia can contribute to the
      neurodegenerative process by releasing a cornucopia of potentially cytotoxic
      substances including the cytotoxic free radical nitric oxide (NO). Although the
      cell signalling events implicated in NO formation in peripheral macrophages are
      well defined, events occurring in the phenotypically homologous cerebral
      microglial cell are not yet fully characterized. 2. In the present study, a
      cloned murine microglial cell line (N9), stimulated with combined
      lipopolysaccharide/interferon-gamma (LPS/IFN) incubation, was shown to produce a
      significant increase in NO formation, as measured by medium nitrite levels,
      during 8-72 h exposure. 3. LPS/IFN-stimulated NO production was partially
      inhibited with the nitric oxide synthase (NOS) competitive antagonists; N(omega)
      nitro-L-arginine methyl ester and N(omega)-nitro-L-arginine. The ability of the
      selective inducible (iNOS) inhibitor, aminoguanidine, but not the selective
      'neuronal-type' constitutive (cNOS) inhibitor 7-nitroindazole, to inhibit NO
      production suggested a primary role of iNOS in this response and was confirmed by
      immunolabelling of activated cells with a specific iNOS antibody. 4. A series of
      tyrosine kinase inhibitors, herbimycin A, genestein, tyrphostins, AG-126, AG-556
      and the tyrosine phosphatase inhibitors, sodium orthovanadate and phenylarsine
      oxide, significantly attenuated LPS/IFN-mediated NO production. The
      serine/threonine kinase inhibitors, staursporine (protein kinase C), H-9 (cyclic
      GMP/cyclic AMP-dependent kinase) or serine/threonine phosphatase inhibitors,
      cyclosporin A (phosphatase 2B) and okadaic acid (phosphatase 1/2A), reduced NO
      formation by an apparent cytostatic mechanism, as determined by cellular
      reduction of 3-(4,5-dimethylthiazol-2-yi)-2,5-diphenyl-tetrazolium bromide (MTT).
      5. The present results suggest that the co-ordinated activation of protein
      tyrosine kinases/phosphatases, and proximal signalling events implicating the
      interplay between serine-threonine kinases/phosphatases, is intricately linked
      with inflammatory mediated mechanisms of iNOS activation in microglial cells by
      regulating the activation of the transcription factor NFkappaB.

PMID- 9535018
TI  - Mechanisms of relaxations of bovine isolated bronchioles by the nitric oxide
      donor, GEA 3175.
AB  - 1. The present study was designed to investigate the effects and mechanisms of
      relaxation induced by the nitric oxide (NO) donor, GEA 3175 (a 3-aryl-substituted
      oxatriazole derivative) on bovine bronchioles (effective lumen diameter 200-800
      microm) suspended in microvascular myographs for isometric tension recording. 2.
      In segments of bovine bronchioles contracted to 5-hydroxytryptamine, GEA 3175
      (10(-8)-10(-4) M) induced concentration-dependent reproducible relaxations. These
      relaxations were slow in onset compared to other NO-donors such as 3
      morpholinosydonimine-hydrochloride (SIN-1) and S-nitroso-N-acetylpenicillamine
      (SNAP). 3. In 5-hydroxytryptamine-contracted preparations the order of relaxant
      potency (pD2) was: salbutamol (7.80) > GEA 3175 (6.18) > SIN-1 (4.90) > SNAP
      (3.55). In segments contracted to acetylcholine, the relaxant responses were
      reduced and GEA 3175 relaxed the bronchioles with pD2 = 4.41 +/- 0.12 and
      relaxations of 66 +/- 10% (n = 4), while SNAP and salbutamol caused relaxations
      of 19 +/- 6% (n = 4) and 27 +/- 6% (n = 8) at the highest concentration used,
      respectively. 4. Oxyhaemoglobin (10(-5) M), the scavenger of nitric oxide, caused
      rightward shifts of the concentration-relaxation curves to GEA 3175 and NO. 1H
      [1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ, 3 x 10(-6) M) and LY 83583 (10(
      6) M), the inhibitors of soluble guanylate cyclase, also reduced the relaxations
      induced by GEA 3175 and nitric oxide. However, ODQ did not affect salbutamol
      evoked relaxation in the bovine small bronchioles. 5. GEA 3175-induced
      relaxations were reduced in potassium-rich (60 mmol l(-1) K+) solution.
      Glibenclamide (10(-6) M) markedly inhibited the relaxations induced by the opener
      of ATP-sensitive K+ channels, levcromakalim (3 x 10(-8)-10(-5) M), but it did not
      modify the relaxations induced by GEA 3175 or salbutamol. Apamin (5 x 10(-7) M),
      a blocker of the small Ca2+-activated K+-channels did not affect the relaxations
      to GEA 3175. In contrast, blockers of large Ca2+-activated K+-channels,
      charybdotoxin (3 x 10(-8)-10(-7) M) and iberiotoxin (10(-8) M), did inhibit the
      relaxations to GEA 3175. The combination of apamin and charybdotoxin did not
      induce an additional inhibitory effect on the relaxations to GEA 3175 compared to
      charybdotoxin alone. 6. In preparations where a concentration-response curve to
      GEA 3175 or NO was first obtained in the presence of LY 83583, incubation with
      charybdotoxin (10(-7) M) did produce an additional inhibitory effect of the
      relaxations. However. in the presence of ODQ (3 x 10(-6) M), iberiotoxin (10(-8)
      M) did not produce additional reduction of the NO- or GEA 3175-induced
      relaxations. 7. The present results suggest that the slow-releasing NO-donor GEA
      3175 is more potent than the traditional NO donors in inducing relaxations of
      bovine bronchioles. GEA 3175, as for exogenously added NO, elicits relaxations
      through a cyclic GMP-dependent mechanism followed by opening of large conductance
      Ca2+-activated K+-channels.

PMID- 9535019
TI  - Inhibition of glycosphingolipid synthesis by threo-1-phenyl-2-decanoylamino-3
      morpholino-1-propanol (PDMP) and the modulation of IL-1beta-stimulated expression
      of inducible nitric oxide synthase in rat aortic smooth muscle cells.
AB  - 1. The composition of glycosphingolipids is altered in atherosclerotic tissue. In
      order to study the possible modulation of interleukin-1beta (IL-1beta)-induced
      expression of inducible nitric oxide synthase (iNOS) by endogenously synthesized
      glycosphingolipids, we investigated rat aortic vascular smooth muscle cells
      (VSMC) grown in the presence of the inhibitor of glycosphingolipid synthesis,
      threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP). 2. Depletion of
      glycosphingolipids by PDMP (20-30 microM) was demonstrated by thin-layer
      chromatography of D-[1-(14)C]-galactose- or L-[-U14C]-serine-labelled
      glycosphingolipids. Nitrite generation was measured by the diaminonaphthalene
      assay, nitric oxide was determined by the oxyhaemoglobin technique and iNOS
      protein was detected by immunocytochemistry. 3. In VSMC grown in the presence of
      PDMP, the glycosphingolipid content was reduced by 30-50%. In PDMP-treated VSMC,
      IL-1beta (3 micro ml[-1])-stimulated release of nitrite (135 +/- 4 nmol mg(-1)
      protein 48 h[-1]) was significantly increased as compared to IL-1beta-stimulated
      control cells (40 +/- 3 nmol mg(-1) protein 48 h(-1); n = 6, P < 0.001).
      Similarly, IL-1beta (3 micro ml(-1), 36 h)-stimulated release of nitric oxide was
      higher in PDMP-treated VSMC (6.1 +/- 0.5 nmol mg(-1) protein h[-1]) as compared
      to untreated cells (2.0 +/- 0.6 nmol mg(-1) protein h(-1); n = 3, P < 0.01).
      These findings were confirmed by the demonstration of increased expression of
      iNOS protein (14.9 +/- 1.2% vs 6.4 +/- 0.2%; n = 4, P < 0.001), as shown by
      immunocytochemistry. 4. Evidence is presented that endogenous glycosphingolipids
      are important modulators of cytokine-induced iNOS expression. In view of an
      altered glycosphingolipid profile in atherosclerotic arteries, these mechanisms
      might be of relevance for the pathogenesis of atherosclerosis and restenosis
      subsequent to vessel injury.

PMID- 9535020
TI  - The mechanism of action of cantharidin in smooth muscle.
AB  - 1. The aim of this study was to investigate the mechanism(s) of the
      vasoconstrictor effect of cantharidin in bovine preparations. 2. Catalytic
      subunits of protein phosphatase type 1 (PP 1) and type 2A (PP 2A) were
      immunologically identified in coronary arteries, isolated smooth muscle cells and
      ventricular myocardium. 3. The mRNAs coding for catalytic subunits of PP 1alpha,
      PP 1beta and PP 2Aalpha were identified by hybridization with specific cDNA
      probes in total RNA from coronary arteries, isolated smooth muscle cells and
      ventricles. 4. The activities of catalytic subunits of PP 1 and PP 2A separated
      by column chromatography from coronary arteries, isolated smooth muscle cells and
      ventricles were inhibited by cantharidin in a concentration-dependent manner. 5.
      Cantharidin increased the phosphorylation state of smooth muscle proteins
      including the regulatory light chains of myosin in 32P-labelled intact smooth
      muscle cells in a concentration-dependent manner. 6. Cantharidin did not affect
      cytosolic calcium concentrations in aortic smooth muscle cells. 7. It is
      suggested that cantharidin contracts smooth muscle preparations by increasing the
      phosphorylation state of regulatory proteins due to inhibition of phosphatase
      activities. Thus, cantharidin might be a useful tool to study the function of
      phosphatases in smooth muscle.

PMID- 9535021
TI  - Reversion of muscarinic autoreceptor agonist-induced acetylcholine decrease and
      learning impairment by dynorphin A (1-13), an endogenous kappa-opioid receptor
      agonist.
AB  - 1. We investigated whether carbachol, a muscarinic receptor agonist, induces
      learning and memory impairment, and if so, dynorphin A (1-13), an endogenous
      kappa-opioid receptor agonist, ameliorates the impairment of learning and memory
      induced by carbachol, by use of a step-through type passive avoidance task. 2.
      Carbachol induced a dose-related dual response. Carbachol (1.66 pmol per rat)
      administered directly into the hippocampus significantly shortened the step
      through latency, while lower (0.166 pmol per rat) and higher (16.6 pmol per rat)
      doses of carbachol did not induce learning or memory impairment. 3. Dynorphin A
      (1-13) (0.5 nmol per rat, i.c.v.) administered 5 min after carbachol injection
      significantly reversed carbachol-induced impairment of learning and memory. 4.
      Perfusion with carbachol (3 x 10(-4) M) significantly decreased acetylcholine
      release in the hippocampus during perfusion as determined by in vivo brain
      microdialysis. This decrease in acetylcholine release was suppressed by co
      perfusion with a low dose of atropine (10(-7) M). 5. Dynorphin A (1-13) (0.5 nmol
      per rat, i.c.v.) immediately before carbachol perfusion completely blocked this
      decrease in extracellular acetylcholine concentration induced by carbachol. 6.
      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) treatment. 7. These results suggest
      that the neuropeptide dynorphin A (1-13) ameliorates the carbachol-induced
      impairment of learning and memory, accompanied by attenuation of the reductions
      in acetylcholine release which may be associated with dysfunction of presynaptic
      cholinergic neurones via kappa-opioid receptors.

PMID- 9535023
TI  - Release of somatostatin and its role in the mediation of the anti-inflammatory
      effect induced by antidromic stimulation of sensory fibres of rat sciatic nerve.
AB  - 1. The effect of antidromic stimulation of the sensory fibres of the sciatic
      nerve on inflammatory plasma extravasation in various tissues and on cutaneous
      vasodilatation elicited in distant parts of the body was investigated in rats
      pretreated with guanethidine (8 mg kg(-1), i.p.) and pipecuronium (200 microg kg(
      1), i.v.). 2. Antidromic sciatic nerve stimulation with C-fibre strength (20 V,
      0.5 ms) at 5 Hz for 5 min elicited neurogenic inflammation in the innervated area
      and inhibited by 50.3 +/- 4.67% the development of a subsequent plasma
      extravasation in response to similar stimulation of the contralateral sciatic
      nerve. Stimulation at 0.5 Hz for 1 h also evoked local plasma extravasation and
      inhibited the carrageenin-induced (1%, 100 microl s.c.) cutaneous inflammation by
      38.5 +/- 10.0% in the contralateral paw. Excitation at 0.1 Hz for 4 h elicited no
      local plasma extravasation in the stimulated hindleg but still reduced the
      carrageenin-induced oedema by 52.1 +/- 9.7% in the paw on the contralateral side.
      3. Plasma extravasation in the knee joint in response to carrageenin (2%, 200
      microl intra-articular injection) was diminished by 46.1 +/- 12.69% and 40.9 +/-
      4.93% when the sciatic nerve was stimulated in the contralateral leg at 0.5 Hz
      for 1 h or 0.1 Hz for 4 h, respectively. 4. Stimulation of the peripheral stump
      of the left vagal nerve (20 V, 1 ms, 8 Hz, 10 min) elicited plasma extravasation
      in the trachea, oesophagus and mediastinal connective tissue in rats pretreated
      with atropine (2 mg kg(-1), i.v.), guanethidine (8 mg kg(-1), i.p.) and
      pipecuronium (200 microg kg(-1), i.v.). These responses were inhibited by 37.8 +/
      5.1%, 49.7 +/- 9.9% and 37.6 +/- 4.2%, respectively by antidromic sciatic nerve
      excitation (5 Hz, 5 min) applied 5 min earlier. 5. Pretreatment with polyclonal
      somatostatin antiserum (0.5 ml/rat, i.v.) or the selective somatostatin depleting
      agent cysteamine (280 mg kg(-1), s.c.) prevented the anti-inflammatory effect of
      sciatic nerve stimulation (5 Hz, 5 min) on a subsequent neurogenic plasma
      extravasation of the contralateral paw skin. The inhibitory effect of antidromic
      sciatic nerve excitation on plasma extravasation in response to vagal nerve
      stimulation was also prevented by somatostatin antiserum pretreatment. 6.
      Cutaneous blood flow assessment by laser Doppler flowmetry indicated that
      antidromic vasodilatation induced by sciatic nerve stimulation was not inhibited
      by excitation of the sciatic nerve of the contralateral leg (1 Hz, 30 min) or by
      somatostatin (10 microg/rat, i.v.) injection. 7. Plasma levels of somatostatin
      increased more than 4 fold after stimulation of both sciatic nerves (5 Hz, 5 min)
      but the stimulus-evoked increase was not observed in cysteamine (280 mg kg(-1),
      s.c.) pretreated rats. 8. These results suggest that somatostatin released from
      the activated sensory nerve terminals mediates the systemic anti-inflammatory
      effect evoked by stimulating the peripheral stump of the sciatic nerve.

PMID- 9535022
TI  - Selective cyclo-oxygenase-2 inhibitors and their influence on the protective
      effect of a mild irritant in the rat stomach.
AB  - 1. The effects of the non-selective cyclo-oxygenase (COX) inhibitor indomethacin
      and the selective COX-2 inhibitors, N-[2-(cyclohexyloxy)-4-nitrophenyl]
      methanesulphonamide (NS-398), 5-methanesulphonamido-6-(2,4-difluorothio-phenyl)-1
      indan one (L-745,337) and 5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulphonyl)
      phenyl-2(5H)-furanone (DFU), on the protection induced by the mild irritant 20%
      ethanol were investigated in the rat stomach. 2. Instillation of 20% ethanol (1
      ml, p.o.) effectively protected against gastric mucosal injury induced by
      subsequent instillation of 70% or 96% ethanol (1 ml, p.o.). 3. Oral
      administration of indomethacin (1.25-20 mg kg[-1]) dose-dependently counteracted
      the protective effect of 20% ethanol (ID50: 3.5 mg kg[-1]). 4. Likewise, NS-398
      (0.1-1 mg kg[-1]), L-745,337 (0.2-2 mg kg[-1]) and DFU (0.02-0.2 mg kg[-1])
      inhibited the protective effect of 20% ethanol in a dose-dependent manner with
      ID50 values of 0.3 mg kg(-1), 0.4 mg kg(-1) and 0.06 mg kg(-1), respectively. 5.
      Inhibition of mild irritant-induced protection was also found when NS-398 (1 mg
      kg[-1]) was administered s.c. or when 96% ethanol was used to damage the mucosa.
      6. Pretreatment with 16,16-dimethyl-prostaglandin (PG)E2 at 4 ng kg(-1), a dose
      that did not protect against ethanol (70%)-induced mucosal damage when given
      alone, completely reversed the effect of the selective COX-2 inhibitors on the
      mild irritant-induced protection. 7. Pretreatment with dexamethasone (3 mg kg(
      1), 24 and 2 h before instillation of 20% ethanol) did not affect the protective
      activity of the mild irritant, indicating that enzyme induction is not involved.
      8. Indomethacin (20 mg kg(-1), p.o.) did not prevent the protection conferred by
      sodium salicylate (100 mg kg[-1]), dimercaprol (30 microg kg[-1]), iodoacetamide
      (50 mg kg[-1]) and lithium (20 mg kg[-1]). Likewise, the protective effect of
      these agents was not counteracted by NS-398 (1 mg kg(-1), p.o.). 9. Whereas
      indomethacin (20 mg kg(-1), p.o.) near-maximally inhibited gastric mucosal
      formation of PGE2, 6-keto-PGF1alpha and thromboxane (TX) B2 as well as platelet
      TXB2 release, the selective COX-2 inhibitors were ineffective. 10. The findings
      show that selective COX-2 inhibitors, although lacking in ulcerogenic activity,
      prevent the protection conferred by a mild irritant. Prostaglandis generated by a
      constitutive COX-2 could thus contribute to physiological functions involved in
      gastric homeostasis, although at present a non-COX-2-related mechanism underlying
      the effect of the selective COX-2 inhibitors tested on mild irritant-induced
      protection cannot be completely excluded.

PMID- 9535024
TI  - Histamine-induced biphasic macromolecular leakage in the microcirculation of the
      conscious hamster: evidence for a delayed nitric oxide-dependent leakage.
AB  - 1. Late effects (up to 3 h) of intravenously-injected histamine on FITC-dextran
      extravasation were investigated in the conscious hamster, by use of computer
      assisted image analysis of fluorescence distribution in a microscopic window of
      dorsal skin fold preparations. This analysis allowed measurement of local (skin)
      and general (all organs) extravasations caused by a bolus injection of histamine
      (1 mg kg(-1), i.v.) 2. Histamine doses higher than 0.01 mg kg(-1) caused biphasic
      local and general extravasations. Initial phases developed fully within 15 min
      (for local) and 60 min (for general) and were followed by late phases beginning
      90 min after histamine injection. Although the initial and late phases of
      histamine-induced extravasations had differential apparent reactivities to the
      autacoid, all the effects of histamine on the microcirculation (1 mg kg[-1]) were
      inhibited by pyrilamine (1 mg kg(-1), i.v.) but not by cimetidine (1 mg kg(-1),
      i.v.). 3. Pretreatment with N(G)-monomethyl-L-arginine (L-NMMA, 30 mg kg(-1),
      i.v.) or N(G)-nitro-L-arginine methyl ester (L-NAME, 100 mg kg(-1), i.v.) did not
      affect the initial phases but did prevent the late phases of local and general
      extravasations triggered by 1 mg kg(-1) histamine. The inhibitory effects of L
      NAME were reversed by L-arginine (30 mg kg[-1]) but not by D-arginine (30 mg kg[
      1]) according to the enantioselectivity of nitric oxide synthase (NOS). A late NO
      mediated venular dilatation occurred in response to plasma histamine. 4. A low
      dose of aminoguanidine (1 mg kg(-1), i.v.), a selective inhibitor of the
      inducible isoform of NOS (iNOS), mimicked the inhibitory effects of L-NAME on the
      late phases of histamine-induced macromolecular extravasations and venular
      dilatation. 5. Pretreatment with dexamethasone (1 mg kg(-1), i.v.) prevented both
      the initial and late phases of histamine-induced extravasations. Fucoidan (1 or
      25 mg kg(-1), i.v.) prevented the late phases without affecting initial phases,
      consistent with a role for leukocytes adhesion in the development of the late NO
      mediated effects of histamine. 6. We conclude that intravenous injection of
      histamine triggers a biphasic inflammatory cascade via initial activation of H1
      receptors which induces a late NO-mediated PMN-dependent extravasation process.

PMID- 9535025
TI  - Possible mechanism of the negative inotropic effect of alpha1-adrenoceptor
      agonists in rat isolated left atria after exposure to free radicals.
AB  - 1. This study was designed to investigate the mechanism(s) of the negative
      inotropic effects of alpha1-adrenoceptor agonists observed in rat isolated left
      atria after exposure to free radicals. 2. Ouabain and calphostin C were used in
      contraction experiments to block the sodium pump and protein kinase C.
      Methoxamine-induced phospholipase C and Na+/K+ ATPase activities were measured.
      3. Methoxamine (300 microM) increased contractile force by 1.6 +/- 0.2 mN in
      control atria but decreased contractile force in electrolysis-treated atria by
      2.0 +/- 0.1 mN (P < 0.05), as determined 10 min after methoxamine addition. In
      contrast, the positive inotropic effects of endothelin-1 (30 nM) and isoprenaline
      (10 microM) were reduced from 2.6 +/- 0.3 to 1.3 +/- 0.1 mN and from 2.6 +/- 0.3
      to 1.7 +/- 0.2 mN, respectively, by electrolysis treatment (P < 0.05), but not
      converted into a negative inotropic action. 4. In an inositol phosphate assay we
      observed that the stimulation of phospholipase C by methoxamine was attenuated by
      electrolysis when the (electrolyzed) medium from the organ bath was used, but the
      phospholipase C responses were restored by the use of fresh medium. However,
      fresh medium did not counteract the negative inotropic effect of methoxamine.
      Accordingly, the negative inotropic effect of methoxamine is not directly related
      to the impaired phospholipase C responses seen in atria subjected to
      electrolysis. 5. Ouabain (10 microM) and the protein kinase C inhibitor
      calphostin C (50 nM), completely prevented the negative inotropic effect of 300
      microM methoxamine in electrolysis-treated atria. 6. Measurement of the Na+/K+
      ATPase activity, revealed that in control atria, alpha1-adrenoceptor stimulation
      with 300 microM methoxamine, decreased the Na+/K+ ATPase activity by 14.4 +/-
      7.7%. In contrast, methoxamine increased the Na+/K+ ATPase activity by 48.8 +/-
      8.9% (P < 0.05) in electrolysis-treated atria. Interestingly, this increase in
      Na+/K+ ATPase activity was completely counteracted by calphostin C (1.4 +/- 0.1%
      over basal). 7. These results indicate that the negative inotropic effects of
      alpha1-adrenoceptor agonists, observed in rat isolated left atria exposed to free
      radicals, are likely to be caused by protein kinase C-mediated phosphorylation
      and subsequent activation of the Na+/K+ ATPase.

PMID- 9535027
TI  - Cannabinoid CB1 receptor and endothelium-dependent hyperpolarization in guinea
      pig carotid, rat mesenteric and porcine coronary arteries.
AB  - 1. The purpose of these experiments was to determine whether or not the
      endothelium-dependent hyperpolarizations of the vascular smooth muscle cells
      (observed in the presence of inhibitors of nitric oxide synthase and cyclo
      oxygenase) can be attributed to the production of an endogenous cannabinoid. 2.
      Membrane potential was recorded in the guinea-pig carotid, rat mesenteric and
      porcine coronary arteries by intracellular microelectrodes. 3. In the rat
      mesenteric artery, the cannabinoid receptor antagonist, SR 141716 (1 microM), did
      not modify either the resting membrane potential of smooth muscle cells or the
      endothelium-dependent hyperpolarization induced by acetylcholine (1 microM) (17.3
      +/- 1.8 mV, n = 4 and 17.8 +/- 2.6 mV, n = 4, in control and presence of SR
      141716, respectively). Anandamide (30 microM) induced a hyperpolarization of the
      smooth muscle cells (12.6 +/- 1.4 mV, n = 13 and 2.0 +/- 3.0 mV, n = 6 in vessels
      with and without endothelium, respectively) which could not be repeated in the
      same tissue, whereas acetylcholine was still able to hyperpolarize the
      preparation. The hyperpolarization induced by anandamide was not significantly
      influenced by SR 141716 (1 microM). HU-210 (30 microM), a synthetic CB1 receptor
      agonist, and palmitoylethanolamide (30 microM), a CB2 receptor agonist, did not
      influence the membrane potential of the vascular smooth muscle cells. 4. In the
      rat mesenteric artery, the endothelium-dependent hyperpolarization induced by
      acetylcholine (1 microM) (19.0 +/- 1.7 mV, n = 6) was not altered by
      glibenclamide (1 microM; 17.7 +/- 2.3 mV, n = 3). However, the combination of
      charybdotoxin (0.1 microM) plus apamin (0.5 microM) abolished the acetylcholine
      induced hyperpolarization and under these conditions, acetylcholine evoked a
      depolarization (7.7 +/- 2.7 mV, n = 3). The hyperpolarization induced by
      anandamide (30 microM) (12.6 +/- 1.4 mV, n = 13) was significantly inhibited by
      glibenclamide (4.0 +/- 0.4 mV, n = 4) but not significantly affected by the
      combination of charybdotoxin plus apamin (17.3 +/- 2.3 mV, n = 4). 5. In the
      guinea-pig carotid artery, acetylcholine (1 microM) evoked endothelium-dependent
      hyperpolarization (18.8 +/- 0.7 mV, n = 15). SR 141716 (10 nM to 10 microM),
      caused a direct, concentration-dependent hyperpolarization (up to 10 mV at 10
      microM) and a significant inhibition of the acetylcholine-induced
      hyperpolarization. Anandamide (0.1 to 3 microM) did not influence the membrane
      potential. At a concentration of 30 microM, the cannabinoid agonist induced a non
      reproducible hyperpolarization (5.6 +/- 1.3 mV, n = 10) with a slow onset. SR
      141716 (1 microM) did not affect the hyperpolarization induced by 30 microM
      anandamide (5.3 +/- 1.5 mV, n = 3). 6. In the porcine coronary artery, anandamide
      up to 30 microM did not hyperpolarize or relax the smooth muscle cells. The
      endothelium-dependent hyperpolarization and relaxation induced by bradykinin were
      not influenced by SR 141716 (1 microM). 7. These results indicate that the
      endothelium-dependent hyperpolarizations, observed in the guinea-pig carotid, rat
      mesenteric and porcine coronary arteries, are not related to the activation of
      cannabinoid CB1 receptors.

PMID- 9535026
TI  - Evidence that spontaneous contractile activity in the rat myometrium is not
      inhibited by NO-mediated increases in tissue levels of cyclic GMP.
AB  - 1. There is conflicting evidence in the literature concerning the role of cyclic
      GMP in the regulation of myometrial contractility and the importance of hormonal
      status on the uterine response to cyclic GMP-elevating agents. The objective of
      the present study was to investigate further the importance of cyclic GMP in the
      control of uterine contractility, by monitoring the effects of cyclic GMP
      elevating agents on spontaneous contractions and cyclic GMP levels in myometrial
      strips from pregnant rats and from ovariectomized rats under the influence of
      oestrogen and/or progesterone. 2. Sodium nitroprusside (SNP) 5 mM, atrial
      natriuretic peptide (ANP) 100 nM, L-arginine 1 mM and 8-bromo-cyclic GMP 100 mM
      had no relaxant effect on the spontaneous contractions of myometria from pregnant
      rats or from ovariectomized rats under the influence of oestrogen or
      progesterone. 3. Tissue levels of cyclic GMP were significantly elevated by SNP
      in all treatment groups, including pregnant animals. For example, in
      ovariectomized, progesterone-treated rats, SNP raised cyclic GMP levels
      approximately 8 fold from a basal level of 2.9 +/- 0.4 pmol mg(-1) protein to
      24.8 +/- 4.0 pmol mg(-1) protein. ANP increased cyclic GMP levels approximately 2
      fold in all treatment groups, except in the pregnant animals. L-Arginine elevated
      cyclic GMP significantly only in ovariectomized, vehicle-treated myometria. 4.
      The activity of cyclic GMP-dependent protein kinase (PKG) was significantly
      increased (3 fold) in myometria exposed to SNP (5 mM). Thus, the inability of SNP
      to relax uterine preparations was not due to a failure of SNP-elevated cyclic GMP
      to activate PKG. 5. The more potent NO donor, S-nitroso-N-acetylpenicillamine
      (SNAP), at a concentration of 100 microM was able to inhibit spontaneous
      contractions significantly in myometrial preparations from both non
      ovariectomized and ovariectomized rats treated with oestrogen or progesterone. 6.
      Tissue levels of cyclic GMP were markedly increased by SNAP at concentrations of
      10, 30 and 100 microM. At 100 microM, cyclic GMP levels increased from 1.9 +/-
      0.2 pmol mg(-1) protein to 74.0 +/- 18.0 pmol mg(-1) protein. However, complete
      or partial blockade of SNAP-induced increases in cyclic GMP levels by the soluble
      guanylyl cyclase inhibitor, ODQ (25 microM), had no effect on the relaxant
      response to SNAP. Thus, the relaxant effect of SNAP in this tissue appears to be
      mediated via a mechanism independent of cyclic GMP. 7. Taken as a whole, the
      results of the present study indicate that cyclic GMP does not play an important
      role in the control of contractility in the rat uterus.

PMID- 9535028
TI  - Inhibitory effect of peptides derived from the N-terminus of lipocortin 1 on
      arachidonic acid release and proliferation in the A549 cell line: identification
      of E-Q-E-Y-V as a crucial component.
AB  - 1. The ability of the glucocorticoid-induced protein lipocortin 1 (LC1) to
      inhibit arachidonic acid release and cell proliferation in A549 cells may be
      mimicked by a sequence taken from the N-terminal, LC1(13-25) (FIENEEQEYVQTV). We
      have now synthesized and tested for biological activity a library of 25 smaller
      peptides derived from this sequence. 2. Peptides were tested in two assays: A549
      cells were prelabelled with tritiated arachidonic acid and thapsigargin (50 nM)
      and EGF (10 nM) used to stimulate the release of this fatty acid. Cell
      proliferation was determined by counting cell numbers following 3 day incubation
      with these peptides, or controls. 3. Many of the peptides were highly insoluble
      but could be more readily dissolved in aqueous solution in the presence of
      commercial liposomes or phosphatidyl serine (5 microM). Since neither of these
      agents alone had any effect on arachidonic acid release or cell proliferation,
      all peptides were tested in the presence of 5 microM phosphatidyl serine. Under
      these conditions LC1(13-25) was active in both assay systems with an IC40 of 40.7
      and 57.0 microM respectively. 4. Deletion of amino acids from the C-terminus of
      the peptide progressively diminished (2-3 fold) the molar potency of LC1(13-25)
      in both assays: after the removal of Val22 biological activity was virtually
      undetectable or very weak (< 30% of LC1[13-25]). 5. Removal of amino acids from
      the N-terminus also lead to a progressive reduction (3-5 fold) in the molar
      potency of the peptides and biological activity became undetectable, or very
      weak, after the removal of Glu18. 6. All active peptides contained the core
      sequence EQEYV(Glu-Gln-Glu-Tyr-Val) which seems to represent a crucial component
      of the pharmacophore, although this sequence on its own was inactive and the
      shortest peptide with significant activity was LC1(18-25) (EQEYVQTV). 7.
      Methoxylation of Tyr21 abolished the ability of LC1(18-25) to inhibit cell
      proliferation and arachidonic acid release. A cyclized version of LC1(18-25) was
      also tested and found to be inactive. 8. LC1(18-25) (178 microM) inhibits cPLA2
      activation in A549 cells as judged by a band-shift assay, whereas equimolar
      concentrations of an inactive peptide LC1(19-25) were without effect in this
      assay system. 9. Several possible mechanisms whereby these peptides act are
      discussed in the light of LC1 biology and of the effect of glucocorticoids on
      cell function.

PMID- 9535029
TI  - Regulation of H1-receptor coupling and H1-receptor mRNA by histamine in bovine
      tracheal smooth muscle.
AB  - 1. Pretreatment of bovine tracheal smooth muscle (BTSM) with histamine (1-100
      microM, 1 h) induced a concentration-dependent desensitization of the contractile
      response to subsequently administered histamine, with a reduction of the maximum
      response of 72 +/- 8% (n = 5) following pre-exposure to 100 microM histamine. In
      contrast, concentration-response curves to the muscarinic agonist, methacholine
      were not affected following histamine pretreatment, indicating a homologous
      desensitization. Furthermore, concentration-response curves to NaF, a G-protein
      activator, were not altered following histamine pre-incubation. 2. The histamine
      H1-receptor (H1R) desensitization could be antagonized by mepyramine (an H1
      receptor antagonist, 1 microM) but not by cimetidine (an H2-receptor antagonist,
      10 microM), indicating that the desensitization occurred via stimulation of
      histamine H1-receptors, without evidence for the involvement of histamine H2
      receptors. 3. Indomethacin (10 microM) did not block the H1R desensitization,
      suggesting no involvement of prostaglandins. Furthermore, histamine pre
      incubation in calcium free medium still induced a functional uncoupling of H1R.
      4. GF 109203X, a protein kinase C (PKC) inhibitor, and H-7, a non-selective
      kinase inhibitor, did not antagonize the homologous H1R desensitization. 5. The
      steady-state level of H1R mRNA, assessed by Northern blot analysis, was not
      affected by prolonged histamine exposure (100 microM, 0.5, 1, 2, 4, 16 and 24 h).
      6. These results suggest that histamine induces desensitization of the H1R at the
      level of the receptor protein, which involves a mechanism independent of PKC,
      PKA, PKG and calcium influx, suggesting the involvement of a receptor-specific
      kinase.

PMID- 9535030
TI  - Influence of applied tension and nitric oxide on responses to endothelins in rat
      pulmonary resistance arteries: effect of chronic hypoxia.
AB  - 1. The effect of basal tension (transmural tensions 235 +/- 29 mg wt (low
      tension: equivalent to approximately 16 mmHg) and 305 +/- 34 mg wt (high tension:
      equivalent to 35 mmHg)) on rat pulmonary resistance artery responses to
      endothelin-1 (ET-1) and the selective ET(B)-receptor agonist sarafotoxin S6c
      (S6c) were studied. The effects of nitric oxide synthase inhibition with N(omega)
      nitro-L-arginine methylester (L-NAME, 100 microM) on ET receptor-induced
      responses, as well as vasodilator responses to acetylcholine (ACh) and S6c, were
      also investigated. Changes with development of pulmonary hypertension, induced by
      two weeks of chronic hypoxia, were determined. 2. Control rat preparations showed
      greatest sensitivity for ET-1 when put under low tension (pEC50: 8.1 +/- 0.1)
      compared with at the higher tension (pEC50: 7.7 +/- 0.1) and there were
      significant increases in maximum contractile responses to S6c (approximately 80%)
      and noradrenaline (approximately 60%) when put under high tension. 3. In control
      pulmonary resistance arteries, both ET-1 and S6c produced potent vasoconstrictor
      responses. S6c was 12 fold more potent than ET-1 in vessels set at low tension
      (S6c pEC50: 9.2 +/- 0.1) and 200 fold more potent than ET-1 when the vessels were
      set at high tension (S6c pEC50: 9.0 +/- 0.1). Chronic hypoxia did not change the
      potencies of ET-1 and S6c but did significantly increase the maximum contractile
      response to ET-1 by 60% (at low tension) and 130% (at high tension). 4. In
      control rat vessels, L-NAME itself caused small increases in vascular tone (5-8
      mg wt tension) in 33-56% of vessels. In the chronic hypoxic rats, in vessels set
      at high tension, L-NAME-induced tone was evident in 88% of vessels and had
      increased to 26.9 +/- 6.6 mg wt tension. Vasodilatation to sodium nitroprusside,
      in non-preconstricted vessels, was small in control rat vessels (2-6 mg wt
      tension) but increased significantly to 22.5 +/- 8.0 mg wt tension in chronic
      hypoxic vessels set at the higher tensions. Together, these results indicate an
      increase in endogenous tone in the vessels from the chronic hypoxic rats which is
      normally attenuated by nitric oxide production. 5. L-NAME increased the
      sensitivity to S6c 10 fold (low tension) and 6 fold (high tension) only in
      chronic hypoxic rat pulmonary resistance arteries. It had no effect on responses
      to ET-1 in any vessel studied. 6. Vasodilatation of pre-contracted vessels by ACh
      was markedly greater in the pulmonary resistance arteries from the chronic
      hypoxic rats (pIC50: 7.12 +/- 0.19, maximum: 72.1 +/- 0.2.0%) compared to their
      age-matched controls (pIC50: 5.77 +/- 0.15, maximum: 28.2 +/- 2.0%). There was
      also a 2.5 fold increase in maximum vasodilatation induced by ACh. 7. These
      results demonstrate that control rat preparations showed greatest sensitivity for
      ET-1 when set at the lower tension, equivalent to the pressure expected in vivo
      (approximately 16 mmHg). Pulmonary hypertension due to chronic hypoxia
      potentiated the maximum response to ET-1. Pulmonary resistance arteries from
      control animals exhibited little endogenous tone, but exposure to chronic hypoxia
      increased endogenous inherent tone which is normally attenuated by nitric oxide.
      Endogenous nitric oxide production may increase in pulmonary resistance arteries
      from chronic hypoxic rats and attenuate contractile responses to ET(B2) receptor
      stimulation. Relaxation to ACh was increased in pulmonary resistance arteries
      from chronic hypoxic rats.

PMID- 9535031
TI  - Induction of nitric oxide synthase by protein synthesis inhibition in aortic
      smooth muscle cells.
AB  - 1. The role of de novo protein synthesis in inducible NO synthase (iNOS)
      activation was investigated in vitro by evaluating the effects of protein
      synthesis inhibitors cycloheximide (CH) and anisomycin (ANI) on iNOS activity,
      protein and mRNA levels in rat aortic smooth muscle cells (RASMC). 2. As
      determined by cyclic GMP accumulation, substrate (L-arginine)- and inhibitor
      (N(G)-monomethyl-L-arginine, NMMA)-sensitive iNOS activity was significantly
      elevated in CH- or ANI-treated RASMC after 24 h. 3. Lipopolysaccharide (LPS)
      produced a time-dependent increase in cyclic GMP levels with maximal stimulation
      at 6 h and a decline to near baseline at 24 h. CH attenuated LPS-induced cyclic
      GMP accumulation at 3 and 6 h. However, cyclic GMP levels were superinduced at
      later times by CH. The concentration-dependence of cyclic GMP stimulation by
      cycloheximide was biphasic both in the absence and presence of LPS, with maximal
      stimulation at 10 microM and inhibition at higher concentrations. 4. Increased
      iNOS activity by CH was associated with elevated levels of immunoreactive iNOS
      protein as judged by Western blotting in LPS- and CH-treated cells. 5. CH-induced
      iNOS activity and superinduction of iNOS by CH in cells treated with LPS were
      both significantly inhibited by actinomycin D, a transcription inhibitor. 6. RT
      PCR revealed elevated iNOS mRNA levels after 12 h of exposure to CH. The
      combination of LPS and CH caused a significant increase in iNOS gene expression
      relative to LPS- or CH stimulation alone. 7. These results show that partial
      protein synthesis inhibition by CH alone upregulates iNOS mRNA and superinduces
      iNOS mRNA in cytokine-treated RASMC, which is translated to the functional enzyme
      generating biologically active NO. Thus iNOS activation in these cells not only
      requires new protein synthesis but it also appears to be negatively regulated by
      newly synthesized proteins.

PMID- 9535032
TI  - Salmeterol inhibition of mediator release from human lung mast cells by beta
      adrenoceptor-dependent and independent mechanisms.
AB  - 1. The long-acting beta2-adrenoceptor agonist, salmeterol (10(-9)-10(-5) M),
      inhibited the IgE-mediated release of histamine from human lung mast cells (HLMC)
      in a dose-dependent fashion. Additional beta-adrenoceptor agonists were studied
      and the rank order of potency for the inhibition of histamine release from HLMC
      was isoprenaline > salmeterol > salbutamol. Approximate EC50 values for the
      inhibition of histamine release were 10 nM for isoprenaline and 100 nM for
      salbutamol. An EC50 value for salmeterol could not be calculated because maximal
      responses to salmeterol were not observed over the concentration range employed.
      2. Both salmeterol and isoprenaline inhibited the generation of
      sulphopeptidoleukotrienes (sLT) more potently and more efficaciously than the
      release of histamine from immunologically-activated HLMC. Salmeterol (EC50 < 0.1
      nM) was more potent than isoprenaline (EC50 0.4 nM) at attenuating sLT
      generation. 3. The beta-adrenoceptor antagonist, propranolol (1 microM), and the
      selective beta2-adrenoceptor antagonist, ICI 118,551 (0.1 microM), both caused
      rightward shifts in the dose-response curve for the inhibition of histamine
      release by isoprenaline. The antagonism of salmeterol effects by propranolol and
      ICI 118,551 was more complex. At lower concentrations (< 1 microM) of salmeterol,
      both antagonists shifted the dose-reponse curve to salmeterol rightward. At a
      higher concentration (10 microM) of salmeterol, neither ICI 118,551 nor
      propranolol was an effective antagonist of the salmeterol-mediated inhibition of
      histamine release. 4. Prolonged exposure (4 h) of HLMC to isoprenaline (1 microM)
      caused an approximately 50% reduction in the effectiveness of a second exposure
      to isoprenaline (10 microM) at inhibiting the release of histamine. whereas this
      pretreatment did not affect the salmeterol (10 microM) inhibition of histamine
      release. 5. Isoprenaline (10(-9)-10(-5) M) caused a dose-dependent increase in
      total cell cyclicAMP levels in purified HLMC which paralleled the inhibition of
      histamine release. Salmeterol (10(-9)-10(-5) M) was considerably less potent than
      isoprenaline at increasing HLMC cyclicAMP levels. 6. In summary, these data
      indicate that salmeterol is an effective inhibitor of the stimulated release of
      mediators from HLMC. The present data also suggest that salmeterol may act to
      inhibit mediator release from HLMC by beta-adrenoceptor-dependent and independent
      mechanisms.

PMID- 9535033
TI  - Reduced sympathetic noradrenergic neurotransmission in the tail artery of Donryu
      rats fed with high cholesterol-supplemented diet.
AB  - 1. Sympathetic neurotransmission and noradrenaline content of the tail artery of
      Donryu rats fed for 2 months with a cholesterol-supplemented diet enriched with
      4% cholesterol, 1% cholic acid, 0.5% thiouracil (CCT), were examined. 2. Total
      serum cholesterol level of CCT fed rats (7.05 +/- 1.77 mg ml(-1), n = 8) was
      significantly greater than lab-chow fed controls (2.58 +/- 0.32 mg ml(-1), n =
      8). Low density lipoprotein level was also significantly increased in CCT-fed
      (1.79 +/- 0.26 mg ml(-1), n = 8) compared with control fed rats (1.35 +/- 0.25 mg
      ml(-1), n = 8) but plasma levels of triglyceride and high density lipoproteins
      did not differ significantly between the two groups. 3. Contractile responses of
      the arterial rings to transmural nerve stimulation (65 V, 0.1 ms, 4-64 Hz, 1 s),
      were markedly attenuated in the CCT fed animals compared with the controls. This
      reduction involved the noradrenergic rather than purinergic component of
      sympathetic transmission. 4. Vasoconstrictor responses to exogenous noradrenaline
      (0.01-300 microM) and adenosine 5'-triphosphate (0.3-1000 microM) were unaffected
      by CCT diet, indicating prejunctional alteration of sympathetic neurotransmission
      during CCT-induced hyperlipidaemia. 5. The noradrenaline content of the tail
      arteries of CCT fed animals (2.64 +/- 0.36 ng mg(-1), n = 6) was significantly
      lower than that of controls (3.82 +/- 0.32 ng mg(-1), n = 6). 6. These findings
      show that chronic treatment of Donryu rats with a cholesterol-supplemented diet
      led to altered levels of circulating lipid fractions accompanied by attenuated
      sympathetic noradrenergic neurotransmission and reduced noradrenaline content of
      the rat tail artery.

PMID- 9535034
TI  - T cell-depleted granulocyte colony-stimulating factor (G-CSF) modified allogenic
      bone marrow transplantation for hematological malignancy improves graft CD34+
      cell content but is associated with delayed pancytopenia.
AB  - To increase the stem cell content of T cell-depleted bone marrow transplants
      (BMT), we treated 12 patients with hematological malignancies with BMT from HLA
      identical sibling donors given G-CSF 10 microg/kg/day for 5 days before marrow
      harvest. After CD34+ cell selection, patients received a median of 1.7 (range,
      0.82-3.1) x 10(6) CD34+ cells/kg and 2.3 (range, 0.25-4.0) x 10(5) CD3+ cells/kg.
      All patients had initial engraftment but four developed pancytopenia between days
      55-130 post-BMT. In two patients, this required a second infusion of G-CSF
      mobilized donor peripheral blood progenitor cells. We observed no delayed
      pancytopenia in a matched historical group of 24 patients receiving T cell
      depleted BMT without prior G-CSF stimulation. Compared to this control group, G
      CSF-stimulated marrow recipients showed a significant decline in neutrophil and
      monocyte counts after 8 weeks. However, outcome after BMT was otherwise
      comparable, with a similar incidence of acute graft-versus-host disease and
      transplant-related mortality. Disease-free survival was 63 vs 67% for controls
      matched for CD34+ cell dose (P = NS). These results indicate that G-CSF
      stimulation can increase the CD34+ cell content of T cell-depleted marrow but
      carries a risk of late graft failure.

PMID- 9535035
TI  - Flow cytometry using annexin V can detect early apoptosis in peripheral blood
      stem cell harvests from patients with leukaemia and lymphoma.
AB  - Quantifying progenitor cells in peripheral blood stem cell (PBSC) harvests by
      flow cytometric enumeration of CD34+ cells does not account for cell viability.
      Cell membrane asymmetry in early apoptosis exposes phosphatidylserine on the cell
      surface. This can be detected by staining with annexin V FITC. Apoptosis in 30
      autologous PBSC harvests mobilised by cyclophosphamide + G-CSF or standard
      chemotherapy + G-CSF was analysed immediately after collection by dual-colour
      flow cytometry with CD34 PE and annexin V FITC. Harvests contained a median of
      3.4 x 10(6)/kg (range 0.3-91.8) CD34+ cells. Of these 87.6% (range 30-96.5) were
      annexin V-. In 10% of harvests more than 50% of CD34+ cells were apoptotic.
      Differences in PBSC mobilisation or collection could not explain the variation in
      annexin V binding. Cyclophosphamide + G-CSF significantly increased the yield of
      CD34+ cells but did not increase apoptosis. Comparison of consecutive harvests
      showed no difference in the numbers of CD34+ cells collected but found a
      significant decrease in apoptotic CD34+ cells through multiple collections.
      Analysis of annexin V binding in PBSC harvests is a simple flow cytometry
      technique which gives additional information on the status of CD34+ progenitor
      cells.

PMID- 9535036
TI  - Unrelated donor bone marrow transplantation in Fanconi anaemia: the Leiden
      experience.
AB  - Fanconi anaemia (FA) is an accepted indication for treatment with allogeneic HLA
      identical BMT. Most patients, however, lack a suitable HLA-identical donor. In
      our centre, six FA patients were transplanted with a matched unrelated donor. Due
      to hypersensitivity to DNA cross-linking agents, a low-dose cyclophosphamide (CY)
      and thoraco-abdominal irradiation (TAI) regimen is recommended for conditioning
      in FA. We added Ara-C upfront and anti-T cell antibodies to enhance engraftment
      and to prevent GVHD, in combination with T cell depletion in four out of six of
      the first transplants. One patient did not engraft. In three patients rejection
      was observed. In three of these four patients a second BMT, using full bone
      marrow grafts, resulted in successful engraftment. The other patient died before
      a second BMT could be performed. The incidence and severity of acute GVHD was
      low: only one patient with grade III acute GVHD was seen. Two out of four
      surviving patients suffered from chronic GVHD. Four patients survived (median
      survival time 43 months after BMT), three with good and one with acceptable
      quality of life. Two patients died, one patient due to adenoviral reactivation
      with multi-organ failure, and one due to sepsis complicated by ARDS. In
      conclusion, MUD BMT is feasible in FA patients with bone marrow failure in whom
      no HLA-identical sibling donor is available. In our study group, the major
      problem was graft rejection, despite the administration of a combination of graft
      enhancing anti-T cell antibodies. Multicentre studies are needed to determine a
      more intensive, but still tolerable, conditioning regimen.

PMID- 9535037
TI  - Autologous stem cell transplantation in chronic myeloid leukaemia using
      Philadelphia chromosome negative blood progenitors mobilised with hydroxyurea and
      G-CSF.
AB  - Autologous transplantation in CML has been a focus of interest over the last few
      years. Determining the indications, optimal timing and method for this procedure
      remains controversial. One approach has been the mobilisation of Philadelphia
      chromosome negative (Ph-) peripheral blood stem cells following high-dose
      chemotherapy as a method of purging the graft. We have described a mobilisation
      regimen of 7 days of hydroxyurea followed by G-CSF and have shown it to be
      substantially less toxic than other methods. We now report further experience
      with this technique in a total of 18 patients and the outcome of transplantation
      in seven patients using cells so-derived. Following mobilisation, approximately a
      third of patients had 100% Ph-collections and half had less than 50% Ph+
      collections. All patients were 100% Ph+ prior to mobilisation. Six out of seven
      transplanted patients showed sustained engraftment and two of these patients
      became 18 and 34% Ph+ 3 months post-transplant. Five patients remain alive and
      well 13 to 25 months post-autograft. In conclusion, we have developed a well
      tolerated regimen for Ph- PBSC mobilisation and have demonstrated that such cells
      are capable of sustained engraftment and of producing significant cytogenetic
      responses.

PMID- 9535038
TI  - Phenotypic and functional reconstitution of peripheral blood lymphocytes
      following T cell-depleted bone marrow transplantation from partially mismatched
      related donors.
AB  - Myeloablative chemotherapy followed by transplantation of a T cell-depleted bone
      marrow graft from a partially mismatched related donor provides a potentially
      curative option for patients with leukemia and other disorders of hematopoiesis,
      although the patient is faced with a period of sustained immunodeficiency as well
      as pharmacologic immunosuppression as a result of prophylaxis against graft
      versus-host disease. Thirty patients who received one to three antigen T cell
      depleted mismatched grafts were evaluated for immune reconstitution. The
      percentage and numbers of cells expressing lymphocyte subset antigens were
      determined by flow cytometry at 14, 28, 60, 100, 180, 270 and 365 days post-BMT
      and at 6 month intervals thereafter. Lymphocyte reconstitution was characterized
      by the early appearance of natural killer cells and a low percentage of both T
      and B cells. During the first year after BMT, the number of NK cells remained
      constant while T and B cells gradually returned to normal numbers and
      proportions. Response to the lymphocyte mitogen phytohemagglutinin returned to
      normal over the course of 2 years, while the response to concanavalin A was
      slightly depressed and the response to pokeweed mitogen became supranormal at
      about 1.5 years and continued to increase. These data suggest the need for long
      term immunophenotypic monitoring as well as prolonged infection surveillance and
      prophylaxis.

PMID- 9535039
TI  - Use of intravenous immune globulin in addition to antiviral therapy in the
      treatment of CMV gastrointestinal disease in allogeneic bone marrow transplant
      patients: a report from the European Group for Blood and Marrow Transplantation
      (EBMT). Infectious Diseases Working Party of the EBMT.
AB  - The best treatment of CMV gastrointestinal disease has been controversial, with
      some centers adding intravenous (i.v.) Ig to antiviral chemotherapy. The aim of
      this retrospective survey was to compare the outcome of antiviral chemotherapy
      with or without i.v. Ig. A questionnaire was sent to centers belonging to the
      EBMT. Thirty-three patients with CMV gastrointestinal disease were reported, 22
      patients were given antiviral chemotherapy alone and 11 patients a combination of
      antiviral chemotherapy and i.v. Ig. Eighteen of 33 (55%) patients responded to
      therapy, 13 of those treated with antiviral chemotherapy alone and five (45%) of
      those treated with the combination (P = NS). Patients with acute GVHD of grades
      II-IV had significantly worse outcomes than patients with acute GVHD grades 0-I.
      In a Cox proportional hazards model corrected for acute GVHD there was no
      difference in outcome of CMV gastrointestinal disease with or without addition of
      Ig. Survival at 100 days after diagnosis of CMV gastrointestinal disease was 64%.
      There was no difference in survival in patients treated with or without i.v. Ig.
      The results of this retrospective survey indicate that addition of i.v. Ig to
      antiviral chemotherapy might not improve outcome in patients with biopsy-proven
      CMV gastrointestinal disease.

PMID- 9535040
TI  - Quality of life and psychological distress of bone marrow transplant recipients:
      the 'time trajectory' to recovery over the first year.
AB  - The purpose of this study was to measure the trajectory of psychosocial recovery
      over the first year after bone marrow transplantation (BMT). BMT patients were
      assessed at baseline (n = 86), hospital discharge (n = 74), 100 days (n = 64) and
      at 1 year (n = 45). Participants completed the Functional Assessment of Cancer
      Therapy-Bone Marrow Transplant Scale (FACT-BMT), the Profile of Mood States Total
      Mood Disturbance Scale (POMS-TMDS), the Medical Outcomes Social Support Survey
      (MOS-SSS), the Center for Epidemiologic Studies-Depression (CES-D) scale
      screener, a performance Status Rating Scale (PSR), and an interview
      questionnaire. The recovery trajectory in this patient population showed three
      distinct trends. The trajectory for distress was linear and improved over time
      with approximately 20% of patients continuing to have psychological distress at 1
      year. Secondly, the trend for overall quality of life was parabolic, worsening at
      discharge, then improving at 100 days and at 1 year. However, there were
      individual areas of deficit at follow-up, eg fatigue, even while overall quality
      of life mean scores improved. Thirdly, the trend for patient concerns over time
      was linear and worsening. These recovery trajectories suggest psychosocial
      interventions before and after BMT that may prepare patients for increasing and
      worsening concerns even as physical well-being improves.

PMID- 9535042
TI  - Simultaneous detection of X and Y chromosomes by two-colour fluorescence in situ
      hybridization in combination with immunophenotyping of single cells to document
      chimaerism after sex-mismatched bone marrow transplantation.
AB  - A powerful approach to documenting engraftment after allogeneic BMT is the
      quantification of the degree of chimaerism in distinct haematopoietic cell
      lineages. This cannot be achieved by the recently developed, quantitative,
      modifications of PCR amplification of highly polymorphic DNA markers, unless this
      technique is applied to separated cell populations. Here, we report the
      development of a new method, in which cells are simultaneously characterized by
      enzymatic immunophenotyping and identified for their origin by two-colour
      fluorescence in situ hybridization with X and Y chromosome-specific DNA probes
      (XY-FISH/immunostaining). The method enables the rapid, reliable and quantitative
      analysis of chimaerism within distinct cell lineages after sex-mismatched BMT,
      without the requirement for cell separation techniques. This is illustrated by
      investigation of the pattern of chimaerism in patients receiving a sex-mismatched
      BMT for the treatment of primary immunodeficiencies. The results obtained with
      the quantitative XY-FISH/immuno staining method show a good correlation with the
      data generated by the semi-quantitative analysis of PCR amplified minisatellites
      in FACS-sorted cell fractions. In addition, XY-FISH/immunostaining was
      successfully applied to detect materno-fetal engraftment of T cells in a SCID
      patient.

PMID- 9535041
TI  - Serial and quantitative analysis of mixed hematopoietic chimerism by PCR in
      patients with acute leukemias allows the prediction of relapse after allogeneic
      BMT.
AB  - Within a prospective study we analyzed hematopoietic chimerism in serial
      peripheral blood samples taken from 55 patients with acute leukemias (ALL 21, AML
      20, MDS 14) with a median age of 13.5 years at very short time intervals
      following allogeneic bone marrow transplantation (allo-BMT). The investigation
      was performed to determine the implications of mixed hematopoietic chimerism (MC)
      with regard to the clinical outcome in patients with acute leukemias after allo
      BMT. Analysis of chimerism was performed by PCR of variable number of tandem
      repeat (VNTR) sequences with a maximum sensitivity of 0.8%. Thirteen male
      patients transplanted with the marrow of a female donor were also studied by
      amplification of a Y-chromosome-specific alphoid repeat (0.1-0.01% sensitivity).
      VNTR analysis in 55 patients revealed complete chimerism (CC) in 36 cases, MC in
      18 follow-ups and autologous recovery in one patient. Quantitative analysis of MC
      identified 10/18 patients with increasing autologous patterns in whom 9/10
      subsequently relapsed. The patient with autologous recovery relapsed as well.
      Eight of 18 patients with MC showed decreasing amounts of autologous DNA and
      became CC upon further follow-up. In contrast, only 7/36 patients with CC in the
      prior analysis of chimerism status relapsed. However, in 4/7 patients the
      interval between last CC confirmation and relapse was more than 4 months. In 2/7
      patients autologous DNA was not detectable in peripheral blood but in bone marrow
      aspirates. One of these seven patients developed a fulminant relapse within 3
      weeks. The probability of relapse-free survival for patients with CC is 0.67 (n =
      36), for patients with decreasing MC 1.0 (n = 8) and for patients with increasing
      MC 0.1 (n = 10). In summary, the results demonstrate that serial and quantitative
      chimerism analysis at short time intervals by PCR provides a reliable and rapid
      screening method for the early detection of recurrence of underlying disease and
      is therefore a prognostic tool to identify patients at highest risk of relapse.

PMID- 9535043
TI  - Computer-based quality control in high-dose chemotherapy and bone marrow
      transplantation.
AB  - High-dose chemotherapy with autologous and allogeneic blood stem cell
      transplantation has become a standard therapy for hematological malignancies and
      solid tumors. To ensure quality of treatment and adherence to internationally
      approved protocols, the use of computer systems has been introduced in some
      oncology centers. Most software packages cannot be used automatically by other
      institutions because of different treatment strategies and medications. To
      overcome this problem, we designed a software system based on an Oracle database,
      which allows the user to develop his own therapy blocks and assemble them to
      generate specific therapy plans. The system supports the daily work of the
      physicians by suggesting medications based on changes in the vital parameters or
      the clinical chemistry. Parameters can be given upper and lower limits whose
      surpassing leads to treatment suggestions by the system. All quantitative
      variables may be depicted in a graphical way. The system is connected to external
      laboratory devices. Export of data to international registries is possible. Until
      now, 43 patients have been transplanted with the help of this system. There is a
      high degree of acceptance among the nursing staff and the physicians. The system
      can be transferred to other centers, if the local hardware and network capacities
      meet the minimal requirements.

PMID- 9535044
TI  - Hematopoietic cell transplantation using plasma and DMSO without HES, with non
      programmed freezing by immersion in a methanol bath: results in 213 cases.
AB  - A simplified cryopreservation method for bone marrow (BM) and peripheral blood
      progenitor cells (PBPC) was utilized in hematopoietic cell transplantation of 213
      patients with hematological or solid neoplasms after ablative chemotherapy (187
      with peripheral blood progenitor cells and 26 with bone marrow). Cells were
      cryopreserved, after addition of autologous fresh plasma with DMSO, without HES,
      by freezing to -80 degrees C in a methanol bath and non-programmed freezer. For
      the patients autotransplanted with PBPC, the median period necessary for recovery
      of more than 0.5 x 10(9)/l granulocytes was 11 days (range 6-44), and 15 (8-204)
      days were required to obtain more than 20 x 10(9)/l platelets. For the patients
      autotransplanted with BM, the median period necessary to recover >0.5 x 10(9)/l
      granulocytes was 12 days (range 9-33), and 24 (12-57) days to obtain more than 20
      x 10(9)/l platelets. These results support this method as being very effective in
      achieving high-quality cryopreservation. The procedure, which uses a non
      programmed freezer, simplifies and reduces enormously the cost of the technical
      measures currently in use, enabling its adoption in almost any clinical
      oncological institution.

PMID- 9535045
TI  - Hyperbaric oxygen therapy in a case of post-total body irradiation colitis.
AB  - We report a 21-year-old man who experienced symptoms of colitis following
      autologous TBI-conditioned PBSC transplantation, which persisted despite
      conventional treatment. Abdominal echography showed a thickened, stratified wall
      of the cecum, of the right colon and of part of the transverse colon. Hyperbaric
      oxygen therapy (20 sessions of 100% oxygen inhalation at 2.5 bar for 120 min in a
      hyperbaric chamber) achieved a prompt clinical recovery as well as complete
      disappearance of the ultrasound abnormalities.

PMID- 9535047
TI  - Successful donor leukocyte transfusion at molecular relapse for a patient with
      acute myeloid leukemia who was treated with allogenic bone marrow
      transplantation: importance of the monitoring of minimal residual disease by WT1
      assay.
AB  - We report here that a patient with relapsed AML after allogeneic bone marrow
      transplantation achieved and maintained complete remission (CR) after effective
      donor leukocyte transfusion (DLT), without the occurrence of GVHD and marrow
      aplasia, for more than 21 months. This continuous CR maintenance is mainly due to
      the application of DLT at molecular relapse that was diagnosed by monitoring
      minimal residual disease (MRD) by the quantitation of WT1 (Wilms tumor gene)
      expression levels (WT1 assay). The present case demonstrates that early
      application of DLT at molecular relapse is essential for the improvement of the
      efficacy of DLT for relapsed AML after BMT.

PMID- 9535046
TI  - Pseudomembraneous clostridium after autologous bone marrow transplantation.
AB  - Clostridium difficile (C. difficile) pseudomembraneous colitis was diagnosed in a
      13-year-old boy with Hodgkin's disease 3 months after autologous bone marrow
      transplantation. Hematopoiesis was fully reconstituted at the time. C. difficile
      infection occurred after gall bladder empyema had been treated conservatively
      with i.v. antibiotics and prophylactic 4-week administration of oral amoxicillin.
      C. difficile colitis was diagnosed early and intensive supportive therapy
      combined with administration of i.v. and subsequently oral vancomycin therapy
      failed. It is a phenomenon rarely seen and successful eradication of the
      clostridium infection was only achieved by a combination of higher dose
      vancomycin with metronidazole. During the post-colitis recovery the patient
      experienced a relapse of Hodgkin's disease and died following further surgical
      intervention 137 days post-transplantation.

PMID- 9535048
TI  - Survival after cytomegalovirus pneumonia in two children receiving autologous
      peripheral blood progenitor cell transplantation (PBPCT).
AB  - Cytomegalovirus (CMV) pneumonia is a very rare but often fatal complication of
      autologous bone marrow or peripheral blood progenitor cell transplantation.
      Diagnosis is usually made by means of CMV antigenemia which is strongly
      predictive of CMV disease. We describe two cases of PBPC transplantation who
      survived after CMV pneumonia which was diagnosed only by bronchoalveolar lavage
      in the absence of CMV-antigenemia.

PMID- 9535049
TI  - Fulminant hepatitis in aplastic anemia: hepatitis G or ALG?

PMID- 9535050
TI  - Is there a relationship between G-CSF response to conditioning regimen and
      engraftment after bone marrow transplantation?

PMID- 9535051
TI  - Medea in hematology.

PMID- 9535052
TI  - Interrelations between hypothalamic somatostatin and proopiomelanocortin neurons.
AB  - Somatostatin receptors were visualized by [125I]-Tyr0-DTrp8-somatostatin
      radioautography on 35% of arcuate neurons containing proopiomelanocortin (POMC)
      mRNA, as identified by in situ hybridization using a [35S] labelled riboprobe on
      5 microm-thick consecutive sections. Furthermore, double immunohistochemical
      staining revealed contacts of beta-endorphin or alpha-MSH containing fibres with
      a majority of somatostatin perikarya in the anterior hypothalamic periventricular
      nucleus. Taken together, these data indicate that hypothalamic somatostatin and
      POMC neurons are interconnected. The results are discussed in term of
      intrahypothalamic control of GH secretion.

PMID- 9535053
TI  - A possible role of the pineal gland in acute immobilization-related suppression
      of naloxone-induced LH release in ovariectomized estrogen-primed rats.
AB  - It has been recently reported that acute immobilization stress almost completely
      suppresses the luteinizing hormone (LH) release induced by naloxone, a mu-opioid
      antagonist, in ovariectomized estrogen-primed rats. The present study examined
      the possible involvement of the pineal gland in the acute immobilization-related
      suppression of the naloxone-induced LH release. An intraventricular (ICV)
      injection of 15 microg naloxone produced an abrupt increase in circulating LH
      concentrations in non-stressed rats. The naloxone-induced LH release was
      completely eliminated when tested 60 min after the end of a 30 min session of
      acute immobilization. The same stress conditions did not affect LH-releasing
      hormone (LHRH)-induced LH release, suggesting that the stress-related suppression
      of the naloxone-induced LH release was a suprapituitary event. In chronically
      pinealectomized rats, but not in sham-pinealectomized rats, naloxone injected 60
      min after the end of the stress session evoked a significant increase in serum LH
      concentrations. However, naloxone injected ICV during the acute immobilization
      did not elicit LH release in either pinealectomized or sham-operated rats. Under
      non-stressed conditions, the LH secretory response to naloxone was similar in
      pinealectomized and sham-operated animals. The same stress (30 min
      immobilization) significantly increased pineal melatonin content as well as
      plasma melatonin concentrations in rats bearing intact pineal glands, indicating
      that stress actually affected the pineal function. These results provide evidence
      for a role of the pineal in the suppression of the LH response to naloxone after
      stress, but not during stress.

PMID- 9535054
TI  - Catecholaminergic control of intracellular free calcium and beta-endorphin
      secretion of rat pituitary intermediate lobe cells.
AB  - Individual melanotropes and intermediate lobes were tested to elucidate the role
      of alpha- and beta-adrenergic and D-2 dopamine receptors in the regulation of
      concentration of intracellular free calcium ([Ca2+]i) and release of beta
      endorphin. Hormone secretion was studied in a superfusion system, while [Ca2+]i
      was measured microspectrofluorimetrically. Noradrenaline (1 microM) resulted in a
      slight decrease, then a marked increase in [Ca2+]i and secretion of beta
      endorphin. The nonselective beta-adrenergic agonist isoproterenol (1 microM)
      increased [Ca2+]i and secretion of beta-endorphin; this effect was blocked by the
      beta-antagonist propranolol (10 microM). The alpha-adrenergic agonist
      phenylephrine (1 microM) increased [Ca2+]i and beta-endorphin secretion, but this
      effect was not blocked by terazosin or prazosin (alpha1-adrenergic antagonists, 1
      microM). Administration of the alpha2-adrenergic agonist xylazine (1 microM)
      increased [Ca2+]i but did not affect secretion of the hormone. Biphasic effect of
      noradrenaline was tested in presence of adrenergic and dopaminergic antagonists.
      The noradrenaline-induced rise in [Ca2+]i and beta-endorphin secretion was
      decreased by propranolol, but this drug did not modify the inhibition. In the
      presence of 1 microM sulpiride (selective D-2 dopaminergic antagonist), the
      inhibitory phase of the curve was abolished, and the subsequent increase was
      reduced. This suggests that activation of dopamine D-2 receptors is involved not
      only in the inhibition, but also in the subsequent increase, which may originate
      from a rebound after the termination of the activation of these inhibitory
      receptors. Our data suggest the presence of several distinct types of
      catecholamine receptors in the rat intermediate lobe, and the dominant
      involvement of D-2 and beta-adrenergic receptors in the noradrenaline-induced
      regulation of melanotropes.

PMID- 9535055
TI  - Aging results in attenuated gonadotropin releasing hormone-luteinizing hormone
      axis responsiveness to glutamate receptor agonist N-methyl-D-aspartate.
AB  - Reproductive aging in the Brown Norway rat occurs because of testicular as well
      as hypothalamic-pituitary dysfunction. Excitatory amino acids (EAA) participate
      in the regulation of pulsatile secretion of hypothalamic GnRH and pituitary LH.
      In the present study, we studied the EAA-GnRH-LH axis for possible age-related
      alterations in prepubertal (35 days), young (3-4 months), middle-aged (12-13
      months) and old (21-23 months) rats. In the first experiment, an intra-atrial
      cannula was implanted in rats of different ages to evaluate the pituitary
      response to small, physiological intravenous bolus administration of GnRH (0.5 or
      1.0 nmol/100 g body weight). The results showed no age-related significant
      differences in in-vivo serum LH or FSH responsiveness to GnRH. In a second
      experiment, blood samples for the gonadotropins were withdrawn immediately before
      and 10 min after an iv injection of the glutamate receptor agonist N-methyl-D
      aspartate (NMDA; 5 mg/kg, a dose that induces a physiological LH pulse in young
      rats). Administration of NMDA induced significant increases in LH and prolactin
      in all groups of animals (P<0.05) and a significant FSH response in young and
      middle-aged but not old rats. NMDA-induced LH, FSH and prolactin release was
      higher (P<0.05) in prepubertal rats than in all other age groups. Compared with
      young rats, NMDA-induced increase in plasma LH and prolactin was lower (P<0.05)
      in old rats. In the third experiment, to ascertain whether this reduced LH
      response to NMDA in old rats was exerted at the hypothalamic level, the effects
      of NMDA on GnRH release in vitro from preoptic area-medial basal hypothalamus
      (POA-MBH) fragments were compared among rats of different ages. GnRH efflux in
      response to NMDA was significantly attenuated with increasing age. GnRH release
      in vitro was higher in prepubertal and lower in old than in young rats (P<0.05).
      Lastly, we measured amino acid concentrations in hypothalamic tissue (POA-MBH
      fragments). Prepubertal rats had higher levels of glutamate and taurine than
      young rats. Significant reductions in glutamate and gamma-aminobutyric acid
      (GABA) levels were found in old compared to young rats. In conclusion, these
      results showed that the hypothalamic NMDA-GnRH-LH axis was altered in old rats.
      The decreased hypothalamic content of some of the EAA and the reduced
      responsiveness of GnRH neurons to NMDA (both in vivo and in vitro) may contribute
      to an altered LH pulsatile secretion observed in old rats.

PMID- 9535056
TI  - Profiles of amyloid precursor and presenilin 2-like proteins are correlated
      during development of the mouse hypothalamus.
AB  - The amyloid precursor protein (APP) and APP-like (APLP) material, as visualized
      with the Mab22C11 antibody, have previously been shown to be associated with
      radial glia in hypothalamus, which are known to promote neurite outgrowth. By
      Northern blot analysis, APP 695 mRNA levels increased steadily over hypothalamic
      development, APP 770 mRNA was transiently expressed at 12 days postnatally, and
      APLP mRNA was only weakly expressed in the hypothalamus. The developmental
      pattern of APP moeities in mouse hypothalamus and in fetal hypothalamic neurons
      in culture was compared with a presenilin 2 (PS2) related protein using an
      antibody developed against the N-terminal part of PS2. By Western blot analysis,
      APP and PS2-like immunoreactivity were visualized as a 100-130 and 52 kDa bands,
      respectively. An APP biphasic increase was observed during hypothalamic
      development in vivo. APP immunoreactivity was equally detected in neuronal and
      glial cultures, while PS2-like material was more concentrated in neurons. A
      correlation between APP/APP-like and PS2-like levels was observed during
      development in vivo. While APP was mostly associated with membrane fractions, a
      significant portion of PS2-like material was also recovered from cytosolic
      fractions in vitro. In contrast to native PS2 in COS-transfected cells, the PS2
      like material did not aggregate after heating for 90 s at 90 degrees C. These
      results indicate a close association between APP and PS2-like material during
      hypothalamic development in vivo, and suggest that neuronal and glial cultures
      may provide appropriate models to test their interactions.

PMID- 9535057
TI  - The nonpeptide growth hormone secretagogue, MK-0677, activates hypothalamic
      arcuate nucleus neurons in vivo.
AB  - There is accumulating evidence that the hypothalamic arcuate nucleus plays an
      important role in mediating the effects of growth hormone secretagogues on growth
      hormone (GH) release from the anterior pituitary gland. One such nonpeptidyl
      secretagogue, MK-0677, has been shown to directly stimulate growth hormone
      release from isolated pituitary cells but its central actions remain to be
      established. Therefore, in the present study, we have employed both
      immunocytochemical and in vivo electrophysiological techniques to examine the
      effects of MK-0677 within the hypothalamic arcuate nucleus of the male rat. In
      conscious male rats, both central and systemic injection of MK-0677 induced fos
      like immunoreactivity specifically within the arcuate nucleus indicating
      selective neuronal activation of neurons within this region. MK-0677 induced
      activation was generally confined close to the wall of the third ventricle,
      whereas systemic injection of the peptide secretagogue, GHRP-6, also induced fos
      like immunoreactivity in more lateral regions of the nucleus. In urethane
      anaesthetized rats, intravenous injection of MK-0677 increased the electrical
      activity of a population of antidromically identified (i.e. neuroendocrine)
      arcuate neurons with a similar electrophysiological profile to cells excited by
      GHRP-6. The activity of neuroendocrine arcuate neurons excited by MK-0677
      injection could be attenuated by a subsequent systemic injection of somatostatin.
      However, the activity of neuroendocrine arcuate neurons unaffected by MK-0677
      injection and the activity of non-neuroendocrine arcuate neurons was unaltered by
      somatostatin injection. Taken together, the immunocytochemical and
      electrophysiological results suggest that systemic and central administration of
      MK-0677 activates a population of neurons in the arcuate nucleus. Furthermore,
      the inhibitory effects of somatostatin on MK-0677-induced excitation of these
      neuroendocrine cells is consistent with an action of neurons involved in the
      regulation of GH release.

PMID- 9535058
TI  - CRFergic innervation of the paraventricular nucleus of the rat hypothalamus: a
      tract-tracing study.
AB  - It has been reported that corticotropin-releasing factor (CRF) may regulate its
      own biosynthesis in the paraventricular nucleus of the hypothalamus (PVH).
      Whether this CRF autoregulation is mediated by local circuitry or from extra-PVH
      CRF neuronal fibers terminating on CRF perikarya within the PVH is unknown. In
      the present study, we sought to determine the origin(s) of this CRF innervation
      using retrograde transport of wheat germ-conjugated-gold particles (WGA-apoHRP
      Au) combined with immunohistochemistry for CRF. The rats also received colchicine
      (100 microg, icv) 5-7 days after tracer injection and were perfused 24 h later.
      Results of retrograde labeling with pressure injections of WGA-apoHRP-Au centered
      to PVH and subsequent immunohistochemical staining for CRF demonstrated numerous
      retrogradely labeled CRF neurons in the perifornical hypothalamic nucleus (PeF),
      the dorsolateral hypothalamic area (DA) (medial and lateral portions) and the
      dorsomedial nucleus of the hypothalamus (DMH). Smaller groups of CRF-ir neurons
      that were retrogradely labeled were found in the bed nuclei of the stria
      terminalis (BnST), the Barrington's nucleus (Bar) and the dorsal raphe (DR).
      These CRFergic pathways to the PVH may represent an anatomical substrate
      underlying the function of the stress-integrative PVH neurons in the autonomic,
      behavioral and neuroendocrine regulation during the stress response, including
      CRF autoregulation.

PMID- 9535059
TI  - Different developmental patterns of melanocortin MC3 and MC4 receptor mRNA:
      predominance of Mc4 in fetal rat nervous system.
AB  - Melanocortins are thought to be involved in neuronal development and
      regeneration. Pro-opiomelanocortin (POMC), the precursor of alpha-melanocyte
      stimulating hormone (alpha-MSH), gamma-MSH, ACTH, and beta-endorphin, becomes
      detectable in rat hypothalamic neurons from gestational day (E) 12.5. We recently
      described stage- and region-specific ontogenetic patterns of binding sites for
      the alpha-MSH analogue [125I]-Nle4,D-Phe7-alpha-MSH ([125I]-NDP), with the first
      localizations in epithalamus and sympathetic chain at E13. [125I]-NDP binds to
      all known melanocortin receptors, including MC3-R and MC4-R, the predominant
      melanocortin receptors in nervous system. To identify the receptor type expressed
      during ontogeny, the developmental pattern of MC3-R and MC4-R mRNA was
      investigated by in situ hybridization in fetuses and offspring of time-pregnant
      Long Evans rats between E14 and postnatal day (P) 27. MC4-R mRNA was found to be
      the predominant species during the entire fetal period. It was localized in all
      fetal areas exhibiting distinct [125I]-NDP binding, starting with sympathetic
      ganglia and epithalamus (E14), and including sensory trigeminal nuclei (E16),
      dorsal motor nucleus of vagus (E16) and cranial nerve ganglia, inferior olive
      (E18) and cerebellum (E18), striatal regions (E16), and entorhinal cortex (E22).
      In contrast, MC3-R mRNA was detectable only in the postnatal period, with a fast
      increase in expression in the ventromedial and arcuate nuclei. The early presence
      of MC4-R mRNA in central and peripheral nervous system and transient regional
      peaks of mRNA expression, often concomitant with periods of neural network
      formation, suggest a role of this receptor type in early ontogeny. The MC3
      receptor may be involved in analogous processes during postnatal development.

PMID- 9535060
TI  - Effect of photostimulation on concentrations of plasma prolactin in castrated
      bantams (Gallus domesticus).
AB  - The annual breeding cycle of 'unimproved' breeds of domestic chicken, including
      the bantam, at temperate latitudes, is terminated by decreasing daylength in
      autumn and is initiated in late winter, while daylengths are still short.
      Observations on photoperiodic birds that terminate seasonal breeding by the
      development of long day photorefractoriness suggest that the photoinduced pattern
      of prolactin secretion is associated with the pattern of gonadal growth and
      regression. It was predicted that, if there is a causal relationship between
      photoinduced changes in prolactin secretion and gonadal function in birds then,
      in the bantam, the pattern of prolactin secretion observed after photostimulation
      would not be the same as in birds terminating breeding by the development of long
      day photorefractoriness. Experiments were carried out on surgically castrated
      bantams to avoid confounding the effects of photostimulation and the stimulatory
      actions of testicular hormones on prolactin secretion. Transfer of photosensitive
      castrated bantams from 8 to 14, 16, 18 or 20 h light/day initially stimulated
      prolactin release and, subsequently, after 20-30 days, concentrations of plasma
      prolactin progressively decreased. After 148 days of photostimulation,
      concentrations of plasma prolactin approached but were still higher than short
      day controls. Transfer of photosensitive castrated bantam cockerels from 8 to 12
      h light/day stimulated a slower increase in plasma prolactin that subsequently
      remained higher than in other photostimulated groups. A further 4 h increase in
      photoperiod in the birds exposed for 148 days to 12 or 16 h light/day resulted,
      respectively, in a transitory increase and no increase in prolactin secretion.
      Recovery of photosensitivity for prolactin release was observed in the birds
      transferred to 18 or 20 h light/day for 148 days after treatment with 8 h
      light/day for 35 days. Attempts to obtain an independent hormonal correlate of
      the prolactin responses to photostimulation by measurement of plasma luteinizing
      hormone (LH) were unsuccessful. The concentration of plasma LH in castrated
      bantams did not change in response to a change in photoperiod. These observations
      show that the photoinduced pattern of prolactin release in the bantam, a species
      which terminates seasonal breeding in response to decreasing daylength, is the
      same as that in birds which terminate seasonal breeding by the development of
      long day photorefractoriness. It is concluded that the photoinduced pattern of
      prolactin secretion in birds can be dissociated from the neuroendocrine
      mechanisms controlling the termination of seasonal breeding.

PMID- 9535061
TI  - Step by painful step: increasing knowledge about laminitis.

PMID- 9535062
TI  - Laparoscopy in the horse: comparative keyhole surgery.

PMID- 9535063
TI  - Environmental control to maintain stabled COPD horses in clinical remission:
      effects on pulmonary function.
AB  - The objective of this study was to test the hypothesis that stabled COPD horses
      can be maintained in clinical remission by replacing hay by grass silage and
      bedding made of wood shavings (Period B) and of wheat straw (Period C) during 6
      weeks, respectively. At the end of these different periods, the pulmonary
      function of the horses was assessed by mechanics of breathing and arterial blood
      analyses. These results were compared to those measured in clinical remission
      obtained after 2 months in pasture (Period A). No significant difference was
      observed between these 3 periods neither to values obtained for healthy horses
      placed during 6 weeks in a hay environment. For all that, COPD horses placed in
      contact with hay in the same barn developed within mean +/- s.d. 8+/-3 days
      clinical signs of heaves and significant alterations of pulmonary function
      parameters.

PMID- 9535064
TI  - Inhibin secretion in the stallion.
AB  - To examine the physiological role of inhibin in the stallion, a heterologous
      radioimmunoassay (RIA) based on a bovine RIA was validated and used to measure
      immunoreactive (ir)-inhibin concentrations in plasma and testicular homogenates.
      The bioactivity of equine testicular inhibin was also examined using an assay for
      suppression of FSH secretion from rat anterior pituitary cells. In addition, to
      identify the cell responsible for secreting testicular inhibin, the localisation
      of inhibin in the testis was investigated by an immunohistochemical method using
      a polyclonal antibody against (Tyr30)-porcine inhibin alpha(1-30) NH2. In the
      RIA, parallel dose response curves were obtained for the bovine inhibin standard
      and serial dilutions of stallion plasma and equine testicular homogenates.
      Parallel FSH inhibition curves were also observed for the bovine inhibin standard
      and serial dilutions of equine testicular homogenates in the bioassay. The
      inhibition of FSH secretion from rat pituitary cells by equine testicular
      homogenates was neutralised by an antiserum against bovine inhibin in vitro.
      Plasma concentrations of ir-inhibin, testosterone and oestradiol-17beta in
      stallions decreased abruptly after bilateral gonadectomy and FSH and LH
      concentrations in the plasma subsequently increased. Therefore, circulating
      inhibin in the stallion appeared to be largely of testicular origin. The
      histochemical results showed for the first time that strong immunopositive
      staining for inhibin occurred in the Leydig cells of the testes. Sertoli cells
      were also stained by the inhibin antibody but the reaction was weaker than that
      in Leydig cells. These results indicate clearly that both Leydig and Sertoli
      cells are potential sources of testicular inhibin in the stallion. A clear
      increase in plasma ir-inhibin concentrations was observed during the natural
      breeding season. Similar seasonal changes in the plasma concentrations of
      testicular steroid hormones and pituitary gonadotrophins occurred throughout the
      year. In conclusion, the testes appear to be the main source of inhibin, and
      testicular inhibin is secreted by Leydig and Sertoli cells in stallions. The
      positive correlations between plasma ir-inhibin and testicular activity during
      both the breeding and nonbreeding seasons indicate that plasma ir-inhibin is a
      useful indicator of reproductive activity in the stallion.

PMID- 9535065
TI  - Laparoscopic intra-abdominal ligation and removal of cryptorchid testes in
      horses.
AB  - Laparoscopic intra-abdominal ligation and removal of cryptorchid testes in horses
      was evaluated retrospectively in 50 horses that underwent the procedure between
      1991 and 1996. Sixty-one cryptorchid testes were removed by one of the following
      methods; the use of 1) an endoscoping stapling and transection device, 2) an
      endoscopic clipping device, 3) an endoscopic ligating loop. Monopolar
      electrosurgery was combined with these methods to facilitate coagulation and
      cutting of tissue. In 8 horses, 9 testes were retained between the internal and
      external inguinal rings. The inguinal testes were removed by cutting the internal
      inguinal ring and bringing the testis back into the abdomen for removal. No
      attempt was made to close the internal inguinal ring. The most frequently
      employed and most cost effective method for laparoscopic intra-abdominal removal
      of cryptorchid testes in this study was the combined use of an endoscopic
      ligating loop and monopolar electrosurgery. One intra-operative complication
      (perforation of the small intestine) occurred and was dealt with successfully.
      One horse developed a fever attributed to upper respiratory tract infection post
      operatively and was treated successfully with antibiotic. Intra-abdominal
      ligation and transection of cryptorchid testes is an effective method for
      cryptorchid castration. This technique minimises the loss of insufflation, allows
      inspection of the cut tissue for haemorrhage and offers secure closure of the
      abdominal wall preventing inguinal herniation and excellent visualisation of the
      cryptorchid testis.

PMID- 9535066
TI  - Equine ulcerative keratomycosis: visual outcome and ocular survival in 39 cases
      (1987-1996).
AB  - The medical records of 39 horses treated for ulcerative keratomycosis over a 10
      year period were reviewed. Records were evaluated to determine the medical and/or
      surgical treatment protocol, visual outcome, globe survival and whether the
      outcome was influenced by the fungal species isolated. Stromal abscesses and iris
      prolapses caused by fungi were not included. Twenty of the horses underwent
      medical treatment only, and 19 horses had combined medical and surgical
      treatment. Most horses had been treated with topical antibiotics (n = 32) and
      atropine sulphate (n = 23) prior to referral; topical antifungals had been
      employed less frequently (n = 14). Fungi were identified by cytology (n = 31),
      culture (n = 33) and/or surgical histopathology (n = 6). Aspergillus (n = 13) and
      Fusarium (n = 10) were the most commonly isolated fungi. Miconazole (n = 35) was
      the most common topical antifungal medication utilised. Median duration of
      treatment was 48 days (range 31-192 days). Associated bacterial infection (n =
      13) was frequently encountered. Visual outcome was favourable in 36/39 (92.3%)
      eyes. All eyes (20/20) retained vision following medical management only, and
      16/19 (84%) retained vision following combined medical and surgical therapy. All
      medically treated horses (20/20), and 17/19 (89%) of those treated medically and
      surgically retained their globes. Overall ocular survival was favourable in 37/39
      (94.9 %) eyes. Aggressive therapy can result in successful results for equine
      ulcerative keratomycosis.

PMID- 9535067
TI  - Measurement of cardiac function by transthoracic echocardiography: day to day
      variability and repeatability in normal Thoroughbred horses.
AB  - In order to assess the reliability and repeatability of transthoracic
      echocardiography for detecting serial changes in cardiac function in horses, day
      to day variability of a number of echocardiographic indices of ventricular
      function were studied. The variables investigated were, from 2-dimensional (2-D)
      and M-mode echocardiography - aortic diameter in systole (Aos), pulmonary artery
      diameter in systole (Pas), left ventricular internal diameter in systole (LLVIDs)
      and diastole (LLVIDd), and left ventricular fractional shortening (%FS) and
      estimated ejection fraction (EF). From pulsed Doppler echocardiography - maximum
      velocity (Vmax) and acceleration (dv/dtmax) of aortic and pulmonary arterial
      blood flow, left and right ventricular velocity time integral (AoVTI and PAVTI)
      and estimated cardiac output (COLV, and CORV), left and right ventricular
      ejection time (LVET and RVET) and pre-ejection period (LVPEP and RVPEP), and
      heart rate. Maximum velocity of early rapid right ventricular filling (ETV) and
      late right ventricular filling due to right atrial contraction (ATV) were
      measured. Maximum deceleration and time for deceleration of early rapid filling
      (dv/dtTV and dt TV) were also determined. Seven healthy mature Thoroughbred
      horses weighing 490-600 kg were studied. The horses' management regimes and
      environment were standardised and an echocardiographic examination was carried
      out on each horse at the same time every day for 6 consecutive days. Two
      statistical measures of repeatability were calculated for each variable: the
      intraclass correlation coefficient (rI) and the 95% confidence intervals for
      error free value of a single measurement. In general, the dimensions and indices
      of cardiac function derived from 2-D and M-mode echocardiography showed better
      repeatability for individual horses than did the indices derived from Doppler
      echocardiography. Overall the 95% confidence intervals for an error-free value of
      all variables derived from Doppler echocardiography were wide. This must be
      appreciated when attributing serial measured changes of Doppler echocardiographic
      variables in an individual animal to effects of a treatment or disease.

PMID- 9535069
TI  - Scintigraphic and clinical findings in the Standardbred metatarsophalangeal
      joint: 114 cases (1993-1995).
AB  - To correlate scintigraphic and clinical findings of the metatarsophalangeal joint
      (MTPJ) in Standardbreds, radiographic findings in horses with confirmed MTPJ
      lameness, and determine if stress reaction and more advanced bone remodelling
      occurred in the MTPJ, medical records of 114 Standardbreds admitted between
      September 1993 and April 1995 in which bone scintigraphy included standing
      lateral and plantar views of the metatarsophalangeal joint (MTPJ) were reviewed.
      Images obtained using a large field of view gamma camera were evaluated visually
      for location, definition and intensity of increased radioisotope uptake (IRU),
      which was graded as mild, moderate, or intense. Clinical history and lameness
      examination findings were recorded and, in horses with documented MTPJ lameness,
      radiographic examination included the 30 degree (down-angled) dorsolateral 45
      degree plantaromedial view thought to be useful in evaluation of the
      plantarolateral condyle of the third metatarsal bone (MtIII). The most common
      abnormality, IRU of the plantarolateral aspect of MtIII, was seen in 67 horses,
      and horses were further classified according to scintigraphic and clinical
      findings. In 43 horses in which lameness was not localised to the MTPJ, mild (32
      horses), moderate (10 horses), and intense (one horse) IRU of MtHII was found. In
      24 horses with lameness localised to the MTPJ, moderate (18 horses) and intense
      (6 horses) IRU was found. Of 18 horses with moderate IRU of MtIII, 9 had
      radiographic evidence of abnormal bony remodelling of MtIII, whereas 5 of 6
      horses with intense IRU had radiographic changes. In 12 horses with MTPJ lameness
      and radiographic evidence of bony remodelling without fracture, radiographic
      changes consisted of plantarolateral subchondral radiolucency and sclerosis (7
      horses), radiolucency and osteochondrosis (one horse), and plantar MtIII
      sclerosis without radiolucency (4 horses). In 2 horses with moderate IRU and MTPJ
      lameness, radiographic evidence of radiolucency and MtIII fracture was found. Of
      19 starters with MTPJ lameness and IRU of MtIII, 18 horses raced after diagnosis,
      but only 13 remained at the same racing class or improved. The results of this
      study suggest the most common scintigraphic abnormality of the MTPJ, IRU of the
      plantarolateral aspect of MtIII, may precede other stress-related changes, and in
      some horses is associated with a continuum of stress-related subchondral bone
      remodelling which results in lameness and later radiographic changes. Since 24 of
      35 horses with moderate or intense IRU of MtIII had MTPJ lameness, and 5 of 7
      horses with intense IRU of MtIII had lameness and radiographic evidence of
      abnormal remodelling, it was concluded that horses with advanced, scintigraphic
      findings are more likely to have lameness and radiographic evidence of
      subchondral bone damage.

PMID- 9535068
TI  - Plasma 5-hydroxytryptamine constricts equine digital blood vessels in vitro:
      implications for pathogenesis of acute laminitis.
AB  - Cumulative concentration response curves to 5-hydroxytryptamine (5-HT; 10(-10)
      10(-4) mol/l) were constructed using isolated rings of equine digital, facial,
      tail and coronary arteries (endothelium intact). 5-HT was 17.7 and 41 times more
      potent as a vasoconstrictor of digital arteries than facial and tail arteries
      respectively. Removal of the endothelium increased the vasoconstrictor potency of
      5-HT in the facial artery by 3.7-fold (P<0.05) but did not alter the sensitivity
      of digital arteries to 5-HT. Coronary arteries failed to contract to 5-HT.
      Coronary arteries pre-contracted with U44069 showed concentration dependent
      relaxation to 5-HT, a response which was partially dependent on the presence of
      the endothelium. No vasorelaxant effects were found in the digital or facial
      arteries. The concentration of 5-HT in platelet poor and platelet rich equine
      plasma was found to be 6.70+/-1.1 x 10(-8) mol/l and 1.77+/-0.36 x 10(-6) mol/l
      (mean +/-s.e.) respectively by high performance liquid chromatography (HPLC).
      Plasma which contained no detectable platelets had a 5-HT concentration of 1.12+/
      0.48 x 10(-8) mol/l. Isolated digital arteries constricted when exposed to
      dilutions of platelet poor and platelet depleted equine plasma. These plasma
      induced contractions were almost completely inhibited by 5-HT receptor
      antagonists, ketanserin and methiothepin. The change in isometric tension in
      rings of equine digital artery in vitro was therefore used as a bioassay for
      plasma 5-HT and the results obtained by this method showed an excellent
      correlation (r2 = 97.2%, P<0.001) with the concentration estimated by HPLC.
      Circulating free concentrations of 5-HT in normal horses may be sufficient to
      constrict digital blood vessels partially in vivo but are well below the
      threshold for contraction of other peripheral blood vessels examined.

PMID- 9535070
TI  - Behavioural changes in stabled horses given nontherapeutic levels of
      virginiamycin.
AB  - Abnormal behaviour commonly develops in intensively managed horses. A possible
      cause is the change in diet occurring when the horse is stabled. An experiment
      was performed to examine this possibility by manipulating the diet with the feed
      supplement virginiamycin, as Founderguard. During 4 weeks, 18 horses were fed
      diets ranging from hay alone to concentrate plus hay in the ratio of 3:1. The
      rations of half the horses given concentrate were supplemented with Founderguard.
      Horses eating high concentrate rations displayed abnormal oral behaviours at a
      higher frequency than those eating only hay. The incidence of these behaviours
      was reduced when diets were supplemented with Founderguard. The drop in faecal pH
      of animals on concentrate diets was also reduced by Founderguard. Animals on
      concentrate diets had an average of 21 kg less gut fill post mortem. Dietary
      supplementation with virginiamycin as Founderguard apparently lessens some
      behavioural problems associated with management of stabled horses and the intake
      of grain. It may allow concentrate to be fed at higher levels than customary
      without adverse behavioural side effects. The suggested mechanism for the
      improved behaviour due to Founderguard supplementation is reduced fermentative
      acidosis in the hindgut.

PMID- 9535071
TI  - Cardiopulmonary changes associated with abdominal insufflation of carbon dioxide
      in mechanically ventilated, dorsally recumbent, halothane anaesthetised horses.
AB  - The use of laparoscopy for the diagnosis or therapeutic management of abdominal
      disease in the horse has distinct advantages when it allows the horse to remain
      standing. However, distending the abdomen by insufflation of a biologically
      active gas in an anaesthetised horse may add to the physiological challenge of
      general anaesthesia and recumbency. The cardiopulmonary responses to abdominal
      insufflation with carbon dioxide (CO2) to 15 mmHg pressure were evaluated in 6
      horses in dorsal recumbency anaesthetised with halothane in oxygen and subjected
      to laparoscopic colopexy. Vaporiser settings targeted a fractional expired
      halothane of 1.5 MAC and a clinically acceptable depth of anaesthesia. Pressure
      and rate controlled positive pressure ventilation was adjusted to an ETCO2 of 35
      mmHg before abdominal insufflation and was not changed thereafter.
      Cardiopulmonary data were collected before, at 30 and 60 min during and 30 min
      after CO2 insufflation. ANOVA for repeated measures followed by Tukey's protected
      t test were used to determine differences. Partial pressure of oxygen and pH of
      arterial blood, tidal volume and systemic vascular resistance decreased during
      abdominal insufflation and laparoscopic surgery whereas mean arterial blood
      pressure, right atrial pressure, cardiac index, stroke index, partial pressure of
      CO2 in arterial blood and end tidal respiratory gases, and calculated
      physiological shunt increased significantly. Only systemic vascular resistance
      returned to the pre-insufflation level after desufflation. The hypercapnia,
      acidosis and apparent increase in cardiac work that accompany CO2
      pneumoperitoneum for laparoscopic surgery could place the anaesthetised horse at
      additional risk of perioperative complications.

PMID- 9535072
TI  - Effects of inhaled beclomethasone dipropionate on respiratory function in horses
      with chronic obstructive pulmonary disease (COPD).
AB  - The effects of beclomethasone dipropionate on pulmonary function and arterial
      blood gas values were investigated in horses with chronic obstructive pulmonary
      disease (COPD). Six mature mares, diagnosed as having COPD based on clinical
      signs, cytological examination of bronchoalveolar lavage and pulmonary function
      testing, were used. Beclomethasone dipropionate (3750 microg) was administered
      b.i.d. for a 2 week period with a metered dose inhaler using a mask. Pulmonary
      function tests and arterial blood gas analyses were performed at weekly
      intervals, starting before beclomethasone administration and for 4 weeks
      thereafter. Upper airway endoscopy and nasopharyngeal fungal cultures were
      performed before and after treatment. Maximal variations in transpulmonary
      pressure (deltaPL) were elevated in all horses at baseline. Beclomethasone
      administration resulted in a significant decrease in deltaPL in 5 horses, and
      deltaPL fell to within the normal range in 4 horses. Two weeks after the end of
      treatment, deltaPL was at or above baseline values in all horses. Total pulmonary
      resistance and elastance decreased significantly during treatment and returned to
      or above baseline values after the administration of beclomethasone was
      discontinued. At baseline, PaO2 range was 53-90 mmHg. In 4 horses with pronounced
      laboured breathing, PaO2 increased with treatment. One horse became reluctant to
      inhale the beclomethasone after one week, and only a transient improvement in
      respiratory function was noted in this animal. One horse developed a mild lower
      airway infection 24 h after the beginning of treatment, but no other possible
      side effects were noticed. Pharyngeal fungal cultures were negative before and
      after treatment. It can be concluded from the results of this study that inhaled
      beclomethasone dipropionate causes a marked improvement of respiratory function
      in horses with COPD.

PMID- 9535073
TI  - Pulmonary vascular pressures of strenuously exercising Thoroughbred horses after
      administration of phenylbutazone and frusemide.
AB  - The present study was carried out to examine the effects of phenylbutazone
      treatment on the pulmonary haemodynamic effects of frusemide in strenuously
      exercising horses. Using catheter mounted manometers, whose in vivo signals were
      referenced at the point of the shoulder, heart rate, right atrial, right
      ventricular and pulmonary vascular pressures were measured in 3 different sets of
      experiments. Seven Thoroughbreds were subjected to 1) control (no medications),
      2) frusemide control and 3) phenylbutazone + frusemide. The experiments were
      carried out in random order and were separated by 7 days. Measurements were made
      at rest and during incremental exercise performed on a treadmill set at 3.5%
      uphill grade. In the frusemide control experiment, horses received frusemide 250
      mg i.v., 4 h pre-exercise. In the phenylbutazone + frusemide experiment, horses
      received 4 i.v. injections of phenylbutazone (4.4 mg/kg bwt) at 12 h intervals.
      Twenty-four hours after the last phenylbutazone injection, horses received
      frusemide 250 mg i.v. and exercise was performed 4 h later. This latter regimen
      mimics prevailing veterinary practice at Illinois racetracks. The highest work
      intensity (14.2 m/s, 3.5% uphill grade) elicited maximal heart rate of horses.
      Significant right atrial, as well as pulmonary arterial, capillary and venous
      hypertension occurred with exertion in all 3 experiments. However, in the
      frusemide-control and the phenylbutazone + frusemide studies, the exercise
      induced rise in mean right atrial and pulmonary vascular pressures was
      significantly (P<0.05) attenuated in comparison with that in the control
      experiments. Statistically significant differences were not found between the
      frusemide control study and the phenylbutazone + frusemide study either at rest
      or during any level of exertion. Therefore, it was concluded that the
      phenylbutazone treatment in our study did not mitigate the pulmonary haemodynamic
      effects of frusemide in strenuously exercising Thoroughbred horses.

PMID- 9535074
TI  - Pharmacokinetics of ceftriaxone in neonatal foals.

PMID- 9535075
TI  - Cortisol, peptides and catecholamines in cerebrospinal fluid, pituitary effluent
      and peripheral blood of ponies.

PMID- 9535076
TI  - Pleuritis associated with perforation of an isolated oesophageal ulcer in a
      horse.

PMID- 9535078
TI  - Terminology in B-mode diagnostic ultrasonography.

PMID- 9535077
TI  - Interstitial pneumonia and pulmonary fibrosis in a horse.

PMID- 9535079
TI  - Specificity of the BvgAS and EvgAS phosphorelay is mediated by the C-terminal HPt
      domains of the sensor proteins.
AB  - Despite the presence of highly conserved signalling modules, significant cross
      communication between different two-component systems has only rarely been
      observed. Domain swapping and the characterization of liberated signalling
      modules enabled us to characterize in vitro the protein domains that mediate
      specificity and are responsible for the high fidelity in the phosphorelay of the
      unorthodox Bvg and Evg two-component systems. Under equimolar conditions,
      significant in vitro phosphorylation of purified BvgA and EvgA proteins was only
      obtained by their histidine kinases, BvgS and EvgS respectively. One hybrid
      histidine kinase consisting of the BvgS transmitter and HPt domains and of the
      EvgS receiver domain (BvgS-TO-EvgS-R) was able to phosphorylate BvgA but not
      EvgA. In contrast, the hybrid protein consisting of the BvgS transmitter and the
      EvgS receiver and HPt domains (BvgS-T-EvgS-RO) was unable to phosphorylate BvgA
      but efficiently phosphorylated EvgA. These results demonstrate that the C
      terminal HPt domains of the sensor proteins endow the unorthodox two-component
      systems with a high specificity for the corresponding regulator protein. In the
      case of the response regulators, the receiver but not the output domains
      contribute to the specific interaction with the histidine kinases, because a
      hybrid protein consisting of the EvgA receiver and the BvgA output domain could
      only be phosphorylated by the EvgS protein.

PMID- 9535080
TI  - The sigmaD-dependent transcription of the ywcG gene from Bacillus subtilis is
      dependent on an excess of glucose and glutamate.
AB  - We investigated the function and transcriptional regulation of ywcG. The protein
      is essential for Bacillus subtilis. Biochemical characterization of the protein
      revealed that it is an FMN-containing NADPH oxidase. ywcG is transcribed
      throughout the whole life cycle of B. subtilis. The start point of transcription
      is preceded by potential promoter sequences for sigmaA, sigmaB and sigmaD. A
      boost in transcription occurs at the beginning of stationary phase in complex
      media containing glutamate and glucose. The induction of transcription at the
      beginning of stationary phase needs the activity of a different alternative sigma
      factor sigmaD. ywcG is, therefore, the first gene with a putative role in energy
      metabolism from B. subtilis that is transcribed in a sigmaD-dependent fashion,
      but its regulation is unique and the reverse of that described for all other
      sigmaD-dependent genes.

PMID- 9535082
TI  - Differential interaction of the transcription factor PrfA and the PrfA-activating
      factor (Paf) of Listeria monocytogenes with target sequences.
AB  - The interaction of the purified PrfA transcription factor with the regulatory
      sequences located upstream of the PrfA-dependent listeriolysin (hly) and
      internalin (inlA) genes was studied in the presence and in the absence of Paf
      (PrfA-activating factor)-containing extracts. It is shown that PrfA protein is
      able to bind, independently of additional factors, to a 109bp DNA fragment
      including the entire hly promoter sequence with the anticipated PrfA binding site
      ('PrfA-box'). PrfA alone, but not in combination with Paf, can also bind to a
      shorter target sequence of 28 bp comprising essentially the PrfA-box of the hly
      promoter. The addition of a Paf-containing extract does not lead to significant
      protein binding to these two hly target sequences in the absence of PrfA but
      converts the complex (CIII) consisting of PrfA and the 109 bp hly DNA fragment to
      a slower migrating PrfA-Paf-DNA complex (CI). Incubation of cell-free extracts of
      wild-type Listeria monocytogenes with the 109 bp DNA fragment leads to the
      formation of CI. The addition of polyclonal PrfA antibodies causes a supershift
      of CIII. Purified PrfA and PrfA-Paf also bind to a DNA fragment containing the
      PrfA-dependent promoter P2 of inlA, albeit at a lower rate when compared with the
      corresponding hly sequence. In contrast to the hly target DNA, the inlA promoter
      sequence efficiently binds Paf alone, and this Paf binding reduces that of PrfA
      and PrfA-Paf to the inlA target DNA. DNase I footprint experiments show that
      purified PrfA protects sequences of dyad symmetry previously proposed as PrfA
      binding sites in the hly and in the inlA promoter regions.

PMID- 9535081
TI  - ClpP of Bacillus subtilis is required for competence development, motility,
      degradative enzyme synthesis, growth at high temperature and sporulation.
AB  - The nucleotide sequence of the Bacillus subtilis clpP gene was determined. The
      predicted protein shows very high similarity to members of the ClpP family of
      proteolytic subunits (68% amino acid sequence identity with that of Escherichia
      coli). We show that ClpP plays an essential role in stationary phase adaptive
      responses. Indeed, a delta clpP mutant was constructed and shown to display a
      pleiotropic phenotype, including a deficiency in both sporulation initiation and
      competence for DNA uptake. The delta clpP mutant has a highly filamentous
      morphology and appears to be non-motile, as judged by swarm plate assays.
      Expression of clpP is strongly induced under heat shock conditions, and ClpP is
      shown to be essential for growth of B. subtilis at high temperature. The role of
      ClpP in the sporulation and competence regulatory pathways was investigated. ClpP
      is required for expression of the spollA and spollG operons, encoding the sigmaF
      and sigmaE sporulation-specific sigma factors. ClpP is also necessary for the
      expression of the comK gene, encoding a positive transcriptional regulator of
      competence genes. ComK-dependent transcription of sacB, encoding the exocellular
      degradative enzyme levansucrase, was found to be abolished in the delta clpP
      mutant. MecA has been characterized previously as a negative regulator of comK
      expression, whose overproduction inhibits both sporulation and competence
      development. Expression of a mecA'-'lacZ translational fusion is shown to be
      increased in the delta clpP mutant. We suggest that ClpP is involved in
      controlling MecA levels in the cell through proteolysis. Increased levels of MecA
      in the absence of ClpP are at least partly responsible for the observed
      pleiotropic phenotype of the delta clpP mutant.

PMID- 9535083
TI  - A competence regulon in Streptococcus pneumoniae revealed by genomic analysis.
AB  - Transformation in bacteria is the uptake and incorporation of exogenous DNA into
      a cell's genome. Several species transform naturally during a regulated state
      defined as competence. Genetic elements in Streptococcus pneumoniae induced
      during transformation were identified by combining a genetic screen with genomic
      analysis. Six loci were discovered that composed a competence-induced regulon.
      These loci shared a consensus promoter sequence and encoded proteins, some of
      which were similar to proteins involved in DNA processing during transformation
      in other bacteria. Each locus was induced during competence and essential for
      genetic transformation.

PMID- 9535084
TI  - Serratia marcescens S-layer protein is secreted extracellularly via an ATP
      binding cassette exporter, the Lip system.
AB  - The Serratia marcescens Lip exporter belonging to the ATP-binding cassette (ABC)
      exporter is known to be involved in signal peptide-independent extracellular
      secretion of a lipase and a metalloprotease. Although the genes of secretory
      proteins and their ABC exporters are usually all reported to be linked in several
      gram-negative bacteria, neither the lipase nor the protease gene is located close
      to the Lip exporter genes, lipBCD. A gene (slaA) located upstream of the lipBCD
      genes was cloned, revealing that it encodes a polypeptide of 100 kDa and is
      partially similar to the Caulobacter crescentus paracrystalline cell surface
      layer (S-layer) protein. The Lip exporter-deficient mutants of S. marcescens
      failed to secrete the SlaA protein. Electron micrography demonstrated the cell
      surface layer of S. marcescens. The S-layer protein was secreted to the cultured
      media in Escherichia coli cells carrying the Lip exporter. Three ABC exporters,
      Prt, Has and Hly systems, could not allow the S-layer secretion, indicating that
      the S. marcescens S-layer protein is strictly recognized by the Lip system. This
      is the first report concerning secretion of an S-layer protein via its own
      secretion system.

PMID- 9535085
TI  - YopJ of Yersinia pseudotuberculosis is required for the inhibition of macrophage
      TNF-alpha production and downregulation of the MAP kinases p38 and JNK.
AB  - Exposure of macrophages to lipopolysaccharide (LPS) leads to production of the
      pro-inflammatory cytokine, tumour necrosis factor alpha (TNF-alpha). Previous
      studies have suggested that pathogenic Yersinia spp. inhibit LPS-mediated
      production of TNF-alpha in macrophages, and that one of the Yop proteins secreted
      by the plasmid-encoded type III pathway is required for this activity. We found
      that TNF-alpha production was inhibited when J774A.1 murine macrophages were
      infected with wild-type Y. pseudotuberculosis but not with an isogenic ysc mutant
      defective for Yop secretion. We inactivated multiple yop genes to identify which
      of these factors are required for the inhibition of TNF-alpha production. A
      mutant unable to express yopJ was defective for the inhibition of TNF-alpha
      production. Production of TNF-alpha is regulated at the transcriptional and
      translational levels by several mitogen-activated protein (MAP) kinases. The MAP
      kinases p38 and JNK underwent sustained activation in macrophages infected with
      the yopJ mutant. Conversely, p38 and JNK were downregulated in macrophages
      infected with the wild-type strain. The ability of the yopJ mutant to
      downregulate p38 and JNK and to inhibit production of TNF-alpha was restored by
      the expression of yopJ+ in trans. Therefore, YopJ is required for Y.
      pseudotuberculosis to downregulate MAP kinases and inhibit the production of TNF
      alpha in macrophages.

PMID- 9535086
TI  - Identification of novel staphylococcal virulence genes by in vivo expression
      technology.
AB  - We have applied in vivo expression technology (IVET) to the study of
      staphylococcal virulence. Using a promoter trap that relies on genetic
      recombination as a reporter of gene expression, we identified 45 staphylococcal
      genes that are induced during infection in a murine renal abscess model. Of
      these, only six were known previously; 11 others have homology to known non
      staphylococcal genes. The known staphylococcal genes include agrA, part of a key
      locus regulating numerous virulence products, and a glycerol ester hydrolase,
      which may enhance staphylococcal survival in abscesses. We constructed 11 strains
      containing mutations in previously unknown ivi genes. Of these strains, seven
      were significantly attenuated in virulence compared with the wild-type parent.
      The mutagenized ivi genes may encode novel staphylococcal virulence factors.

PMID- 9535087
TI  - Identification of a regulatory protein required for pressure-responsive gene
      expression in the deep-sea bacterium Photobacterium species strain SS9.
AB  - Here, we report the characterization of a gene necessary for hydrostatic pressure
      regulation of gene expression in the deep-sea bacterium Photobacterium species
      strain SS9. The deduced amino acid sequence of the gene product shares extensive
      similarity to ToxR, a transmembrane DNA-binding protein first discovered as a
      virulence determinant in the pathogenic bacterium Vibrio cholerae. Changes in
      hydrostatic pressure induce changes in both the abundance and the activity of the
      SS9 ToxR protein (or the activity of a ToxR-regulated protein). As with other
      high-pressure-inducible phenomena observed in higher organisms, anaesthetics
      antagonize high-pressure signalling mediated by ToxR. It is suggested that SS9
      ToxR has evolved the ability to respond to pressure-mediated alterations in
      membrane structure. V. cholerae and SS9 also share similarity in a ToxR-regulated
      protein, indicating that part of the ToxR regulon is conserved in diverse members
      of the family Vibrionaceae. The SS9 ToxR system represents a useful model for
      studies of signal transduction and environmental adaptation in the largest
      portion of the biosphere, the deep sea.

PMID- 9535088
TI  - An AUG initiation codon, not codon-anticodon complementarity, is required for the
      translation of unleadered mRNA in Escherichia coli.
AB  - We determined the in vivo translational efficiency of 'unleadered' lacZ compared
      with a conventionally leadered lacZ with and without a Shine-Dalgarno (SD)
      sequence in Escherichia coli and found that changing the SD sequence of leadered
      lacZ from the consensus 5'-AGGA-3' to 5'-UUUU-3' results in a 15-fold reduction
      in translational efficiency; however, removing the leader altogether results in
      only a twofold reduction. An increase in translation coincident with the removal
      of the leader lacking a SD sequence suggests the existence of stronger or novel
      translational signals within the coding sequence in the absence of the leader. We
      examined, therefore, a change in the translational signals provided by altering
      the AUG initiation codon to other naturally occurring initiation codons (GUG,
      UUG, CUG) in the presence and absence of a leader and find that mRNAs lacking
      leader sequences are dependent upon an AUG initiation codon, whereas leadered
      mRNAs are not. This suggests that mRNAs lacking leader sequences are either more
      dependent on perfect codon-anticodon complementarity or require an AUG initiation
      codon in a sequence-specific manner to form productive initiation complexes. A
      mutant initiator tRNA with compensating anticodon mutations restored expression
      of leadered, but not unleadered, mRNAs with UAG start codons, indicating that
      codon-anticodon complementarity was insufficient for the translation of mRNA
      lacking leader sequences. These data suggest that a cognate AUG initiation codon
      specifically serves as a stronger and different translational signal in the
      absence of an untranslated leader.

PMID- 9535090
TI  - Control of expression of LlaI restriction in Lactococcus lactis.
AB  - The plasmid encoded LlaI R/M system from Lactococcus lactis ssp. lactis consists
      of a bidomain methylase, with close evolutionary ties to type IIS methylases, and
      a trisubunit restriction complex. Both the methylase and restriction subunits are
      encoded on a polycistronic 6.9 kb operon. In this study, the 5' end of the llal
      6.9 kb transcript was determined by primer extension analysis to be 254 bp
      upstream from the first R/M gene on the operon, llalM. Deletion of this promoter
      region abolished LlaI restriction in L. lactis. Analysis of the intervening
      sequence revealed a 72-amino-acid open reading frame, designated llalC, with a
      conserved ribosome binding site and helix-turn-helix domain. Overexpression of
      llalC in Escherichia coli with a T7 expression vector produced the predicted
      protein of 8.2 kDa. Mutation and in trans complementation analyses indicated that
      C-LlaI positively enhanced LlaI restriction activity in vivo. Northern analysis
      and transcriptional fusions of the llal promoter to a lacZ reporter gene
      indicated that C x LlaI did not enhance transcription of the llal operon.
      Databank searches with the deduced protein sequence for llalC revealed
      significant homologies to the E. coli Rop regulatory and mRNA stabilizer protein.
      Investigation of the effect of C x LlaI on enhancement of LlaI restriction in L.
      lactis revealed that growth at elevated temperatures (40 degrees C) completely
      abolished any enhancement of restriction activity. These data provide molecular
      evidence for a mechanism on how the expression of a restriction system in a
      prokaryote can be drastically reduced during elevated growth temperatures, by a
      small regulatory protein.

PMID- 9535089
TI  - Modulations in lipid A and phospholipid biosynthesis pathways influence outer
      membrane protein assembly in Escherichia coli K-12.
AB  - The assembly defect of a mutant outer membrane protein, OmpF315, can be corrected
      by suppressor mutations that lower lipopolysaccharide (LPS) levels and indirectly
      elevate phospholipid levels. One such assembly suppressor mutation, asmB1, is an
      allele of lpxC (envA) whose product catalyses the first rate-limiting step in the
      lipid A (LPS) biosynthesis pathway. Besides reducing LPS levels, asmB1 confers
      sensitivity to MacConkey medium. A mutation, sabA1, that reverses the MacConkey
      sensitivity phenotype of asmB1 maps within fabZ (whose product is needed for
      phospholipid synthesis from a precursor) is also required for lipid A synthesis.
      In addition to reversing MacConkey sensitivity, the sabA1 mutation reverses the
      OmpF315 assembly suppression phenotype of asmB1. These results show that OmpF315
      assembly suppression by asmB1, which is achieved by lowering LPS levels, can be
      averted by a subsequent aberration in phospholipid synthesis at a point where the
      biosynthetic pathways for these two lipid molecules split. OmpF315 assembly
      suppression can also be achieved in an asmB+ background where FabZ expression is
      increased. The data obtained in this study provide genetic evidence that elevated
      phospholipid levels and/or phospholipid to LPS ratios are necessary for assembly
      suppression.

PMID- 9535091
TI  - Identification of the Chi site of Haemophilus influenzae as several sequences
      related to the Escherichia coli Chi site.
AB  - The Escherichia coli Chi site 5'-GCTGGTGG-3' modulates the activity of the
      powerful dsDNA exonuclease and helicase RecBCD. Genome sequence analyses revealed
      that Chi is frequent on the chromosome and oriented with respect to replication
      on the E. coli genome. Chi is also present much more frequently than predicted
      statistically for a random 8-mer sequence. Although it is assumed that Chi is
      ubiquitous, there is virtually no proof that its features are conserved in other
      microorganisms. We therefore identified and analysed the Chi sequence of an
      organism for which the full genome sequence was available, Haemophilus
      influenzae. The biological test we used is based on our finding that rolling
      circle plasmids provide a specific substrate for RecBCD analogues in different
      microorganisms. Unexpectedly, several related sequences, corresponding to 5'
      GNTGGTGG-3' and 5'-G(G/C)TGGAGG-3', showed Chi activity. As in E. coli, the H.
      influenzae Chi sites are frequent on the genome, which is in keeping with the
      need for frequent Chi sites for dsDNA break repair of chromosomal DNA. Although
      statistically over-represented, this feature is less marked than that of the E.
      coli Chi site. In contrast to E. coli, the H. influenzae Chi motifs are only
      slightly oriented with respect to the replication strand. Thus, although Chi
      appears to have a highly conserved biological role in attenuating exonuclease
      activity, its sequence characteristics and statistical representation on the
      genome may differ according to the particular features of the host.

PMID- 9535092
TI  - Transcription-repair coupling factor is involved in carbon catabolite repression
      of the Bacillus subtilis hut and gnt operons.
AB  - A Bacillus subtilis mutant that partially relieves carbon catabolite repression
      (CCR) of the hut operon was isolated by transposon mutagenesis. Characterization
      of this mutant revealed that the transposon had inserted into the gene, mfd, that
      encodes transcription-repair coupling factor. The Mfd protein is known to promote
      strand-specific DNA repair by displacing RNA polymerase stalled at a nucleotide
      lesion and directing the (A)BC excinuclease to the DNA damage site. A set of
      transcriptional lacZ fusions was used to demonstrate that the mfd mutation
      relieves CCR of hut and gnt expression at the cis-acting cre sequences located
      downstream of the transcriptional start site but does not affect CCR at sites
      located at the promoters. CCR of the amyE and bglPH genes, which contain cre
      sequences that overlap their promoters, is not altered by the mfd mutation. These
      results support a model in which the Mfd protein displaces RNA polymerase stalled
      at downstream cre sites that function as transcriptional roadblocks and reveal a
      new role for Mfd in cellular physiology.

PMID- 9535093
TI  - nodD2 of Rhizobium sp. NGR234 is involved in the repression of the nodABC operon.
AB  - Transcriptional regulators of the lysR family largely control the expression of
      bacterial symbiotic genes. Rhizobium sp. NGR234 contains at least four members of
      this family: two resemble nodD, while two others are more closely related to
      syrM. Part of the extremely broad host range of NGR234 can be attributed to
      nodD1, although the second gene shares a high degree of DNA sequence homology
      with nodD2 of R. fredii USDA191. A nodD2 mutant of NGR234 was constructed by
      insertional mutagenesis. This mutant (NGR omega nodD2) was deficient in nitrogen
      fixation on Vigna unguiculata and induced pseudonodules on Tephrosia vogelii.
      Several other host plants were tested, but no correlation could be drawn between
      the phenotype and nodule morphology. Moreover, nodD2 has a negative effect on the
      production of Nod factors: mutation of this gene results in a fivefold increase
      in Nod factor production. Surprisingly, while the structure of Nod factors from
      free-living cultures of NGR omega nodD2 remained unchanged, those from V.
      unguiculata nodules induced by the same strain are non-fucosylated and have a
      lower degree of oligomerization. In other words, developmental regulation of Nod
      factor production is also abolished in this mutant. Competitive RNA
      hybridizations, gene fusions and mobility shift assays confirmed that nodD2
      downregulates expression of the nodABC operon.

PMID- 9535094
TI  - Dominant C-terminal deletions of FtsZ that affect its ability to localize in
      Caulobacter and its interaction with FtsA.
AB  - The cell division protein FtsZ is composed of three regions based on sequence
      similarity: a highly conserved N-terminal region of approximately 320 amino
      acids; a variable spacer region; and a conserved C-terminal region of eight amino
      acids. We show that FtsZ mutants missing different C-terminal fragments have
      dominant lethal effects because they block cell division in Caulobacter
      crescentus by two different mechanisms. Removal of the C-terminal conserved
      region, the linker, and 40 amino acids from the end of the N-terminal conserved
      region (FtsZdeltaC281) prevents the localization or the polymerization of FtsZ.
      Because two-hybrid analysis indicates that FtsZdeltaC281 does not interact with
      FtsZ, we hypothesize that FtsZdeltaC281 blocks cell division by competing with a
      factor required for FtsZ localization or that it titrates a factor required for
      the stability of the FtsZ ring. The removal of 24 amino acids from the C-terminus
      of FtsZ (FtsZdeltaC485) causes a punctate pattern of FtsZ localization and
      affects its interaction with FtsA. This suggests that the conserved C-terminal
      region of FtsZ is required for proper polymerization of FtsZ in Caulobacter and
      for its interaction with FtsA.

PMID- 9535097
TI  - Is the dnaA promoter region in Escherichia coli an evolutionary junkyard of
      physiologically insignificant regulatory elements?

PMID- 9535095
TI  - Chemotactic response regulator mutant CheY95IV exhibits enhanced binding to the
      flagellar switch and phosphorylation-dependent constitutive signalling.
AB  - CheY, a response regulator protein in bacterial chemotaxis, mediates swimming
      behaviour through interaction with the flagellar switch protein, FliM. In its
      active, phosphorylated state, CheY binds to the motor switch complex and induces
      a change from counterclockwise (CCW) to clockwise (CW) flagellar rotation. The
      conformation of a conserved aromatic residue, tyrosine 106, has been proposed to
      play an important role in this signalling process. Here, we show that an
      isoleucine to valine substitution in CheY at position 95--in close proximity to
      residue 106--results in an extremely CW, hyperactive phenotype that is dependent
      on phosphorylation. Further biochemical characterization of this mutant protein
      revealed phosphorylation and dephosphorylation rates that were indistinguishable
      from those of wild-type CheY. CheY95IV, however, exhibited an increased binding
      affinity to FliM. Taken together, these results show for the first time a
      correlation between enhanced switch binding and constitutive signalling in
      bacterial chemotaxis. Considering present structural information, we also propose
      possible models for the role of residue 95 in the mechanism of CheY signal
      transduction.

PMID- 9535096
TI  - The InIB protein of Listeria monocytogenes is sufficient to promote entry into
      mammalian cells.
AB  - InIB is one of the two Listeria monocytogenes invasion proteins required for
      bacterial entry into mammalian cells. Entry into human epithelial cells such as
      Caco-2 requires InIA, whereas InIB is needed for entry into cultured hepatocytes
      and some epithelial or fibroblast cell lines such as Vero, HEp-2 and HeLa cells.
      InIB-mediated entry requires tyrosine phosphorylation, cytoskeletal
      rearrangements and activation of the host protein phosphoinositide (PI) 3-kinase,
      probably in response to engagement of a receptor. In this study, we demonstrate
      for the first time that InIB is sufficient to promote internalization. Indeed,
      coating of normally non-invasive bacteria or inert latex beads with InIB leads to
      internalization into mammalian cells. In addition, a soluble form of InIB also
      appears to promote uptake of non-invasive bacteria, albeit at a very low level.
      Similar to entry of L. monocytogenes, uptake of InIB-coated beads required
      tyrosine phosphorylation in the host cell, PI 3-kinase activity and cytoskeletal
      reorganization. Taken together, these data indicate that InIB is sufficient for
      entry of L. monocytogenes into host cells and suggest that this protein is an
      effector of host cell signalling pathways.

PMID- 9535098
TI  - Dopamine synthesizing enzymes in paraventricular hypothalamic neurons of the
      human and monkey (Macaca fuscata).
AB  - Using immunohistochemistry, we demonstrated that paraventricular hypothalamic
      neurons immunoreactive for tyrosine hydroxylase (TH) were not immunopositive for
      the second step catecholamine synthesizing enzyme L-amino acid decarboxylase
      (AADC) in the human and monkey Macaca fuscata. In the latter species, they were
      not immunoreactive for dopamine. It is most likely that primate paraventricular
      TH-containing neurons do not synthesize dopamine.

PMID- 9535099
TI  - D1 agonist CY208-243 attenuates the pattern electroretinogram to low spatial
      frequency stimuli in the monkey.
AB  - We investigated whether or not the D1 agonist, CY 208-243, affects the spatial
      tuning function of pattern electroretinogram (PERG). Two lightly anaesthetised
      monkeys were studied before and after CY 208-243 or placebo administration. The
      results show that the PERG response to 0.5 cycles/degree (c/d; coarse), but not
      to 2.3 c/d (medium) spatial frequency stimuli disappears following systemic
      administration of this drug. Since previous results show that D2 blockers
      attenuate the PERG only above 2.3 c/d, foremost the peak of the normal spatial
      frequency response function, the current results suggest that dopamine itself,
      via D1 receptors, may be responsible for the low spatial frequency decline of
      normal spatial PERG tuning function. We infer that the synergistic activation of
      D1 and D2 receptors is needed to shape the spatially tuned primate ERG.

PMID- 9535100
TI  - Comparison of glycine- and GABA-evoked currents in two types of neurons isolated
      from the rat striatum.
AB  - Strychnine-sensitive glycine-activated currents and gamma-aminobutyric acid
      (GABA)-activated currents were compared in two types of neurons acutely isolated
      from striatal slices by vibrodissociation: large cells, presumably cholinergic
      giant aspiny neurons (GAN) and medium sized cells, presumed medium spiny neurons
      (MSN). Whole cell voltage clamp and concentration jump techniques were used. All
      cells responded to glycine (10-1000 microM) and GABA (2-100 microM), in MSN and
      GAN the maximal responses to glycine were 50 and 120% of the GABA response,
      respectively. GABA- and glycine- responses were additive and blocked selectively
      by bicuculline (1 microM) and strychnine (50 nM), respectively. These results
      predict the presence of alpha- and beta-subunits of the glycine receptor in the
      striatum.

PMID- 9535101
TI  - Trk neurotrophin receptor family immunoreactivity in rat and human pituitary
      tissues.
AB  - Several lines of evidence suggest that neurotrophins may be involved in pituitary
      function. By immunocytochemical methods we analyzed the cellular distribution of
      their functional receptors in the pituitary gland. In the rat pituitary gland
      Trks were differentially distributed. Punctate immunoreactivity for TrkA was
      observed within the neural lobe, whereas numerous nerve endings were
      immunostained for TrkB and TrkC in the intermediate lobe. Endocrine cells of the
      intermediate lobe exhibited intense immunoreactivity for the three Trks, whereas
      scattered endocrine cells of the anterior lobe displayed a robust immunostaining
      for TrkC. In addition, TrkA and TrkB immunoreactivity was located in normal and
      neoplastic endocrine cells from human pituitary adenomas. The differential
      distribution of Trks in the hypophysis suggests a potential role of different
      neurotrophins in pituitary functions.

PMID- 9535102
TI  - Serotonin stimulates corticotropin-releasing factor gene expression in the
      hypothalamic paraventricular nucleus of conscious rats.
AB  - To examine the direct effects of serotonin (5-HT) on the release and synthesis of
      corticotropin-releasing factor (CRF) in the hypothalamic paraventricular nucleus
      (PVN), 5-HT was microinjected just onto the bilateral PVN of conscious rats.
      Plasma adrenocorticotropic hormone (ACTH) levels peaked at 30 min and returned to
      the basal levels in 90 min. Northern blot analysis revealed that the CRF
      messenger RNA (mRNA) level in the PVN as well as the proopiomelanocortin mRNA
      level in the anterior pituitary significantly increased 120 min after the 5-HT
      injections (50-250 nmol/side). Pretreatment with intracerebroventricular (i.c.v.)
      injection of pindobind 5-HT1A (5 nmol) or LY-278584 (500 nmol) completely
      abolished the 5-HT-induced ACTH response, whereas LY-53857 (100 nmol) was without
      effect. These results suggest that 5-HT stimulates CRF release, which has
      interactions with 5-HT1A and 5-HT3 receptors on CRF neurons in the PVN, and
      activates CRF synthesis in conscious rats.

PMID- 9535103
TI  - Urocortin-like immunoreactivity in the substantia nigra, ventral tegmental area
      and Edinger-Westphal nucleus of rat.
AB  - Neurons showing intense urocortin-like immunoreactivity (Ucn-IR) were found
      immunohistochemically in the substantia nigra pars compacta (SNc) and ventral
      tegmental area (VTA), as well as in Edinger-Westphal nucleus (E-W), in the rat
      brain. Almost all Ucn-immunoreactive neuronal cell bodies in the SNc and VTA
      showed immunoreactivity for tyrosine hydroxylase. Injection of a retrograde
      tracer, colloidal gold-labeled WGAapoHRP, into the cervical spinal cord resulted
      in labeling of some E-W neurons with Ucn-IR. These findings suggest that Ucn is
      located in the cell bodies of dopaminergic neurons, as well as in the cell bodies
      of E-W neurons sending axons to the spinal cord.

PMID- 9535104
TI  - Stimulatory effect of lymphocyte-derived factor on catecholamine efflux from
      cultured bovine adrenal medullary cells.
AB  - The effects of lymphocytes and their conditioned medium on catecholamine efflux
      and uptake were examined in cultured bovine adrenal medullary cells. Co-culture
      of adrenal medullary cells with lymphocytes for 3 days caused an increase in
      appearance of catecholamines in the culture medium. Treatment of adrenal
      medullary cells with a conditioned medium prepared from lymphocytes also enhanced
      the appearance of catecholamines in culture medium in time- (8-48 h) and
      concentration-dependent manners. Heat treatment of the conditioned medium at 60
      and 100 degrees C for 10 min reduced its stimulatory effect to 59 and 20% of
      control, respectively. After gel filtration on a Sephadex G-25 column or dialysis
      (<8 kDa molecular mass cutoff), the stimulatory activity of the conditioned
      medium was found in a high molecular fraction. The conditioned medium had little
      effect on the activity of lactate dehydrogenase in the medium of cultured adrenal
      medullary cells and on desipramine-sensitive [3H]norepinephrine uptake by the
      cells. These findings suggest that lymphocytes release a heat-sensitive factor(s)
      (molecular mass of more than 8 kDa) which increases efflux of catecholamines from
      cultured adrenal medullary cells.

PMID- 9535105
TI  - Age-dependent changes in androgen receptor immunoreactivity in motoneurons of the
      spinal nucleus of the bulbocavernosus of male rats.
AB  - Androgen receptor (AR) immunoreactivity was examined in androgen-sensitive
      motoneurons of the spinal nucleus of the bulbocavernosus (SNB) in young and old
      male rats by immunohistochemistry using the polyclonal antibody, PG21. In young
      animals, intense AR immunoreactivity was confined to the cell nucleus, but not in
      the nucleolus of SNB motoneurons. In old animals, both the intensity of AR
      immunoreactivity in the nuclei and number of AR immunoreactive nuclei of the SNB
      motoneurons were significantly reduced. Plasma levels of testosterone in old
      animals were significantly smaller than those in young ones. Age-dependent
      changes both in AR expression of SNB motoneurons and plasma levels of androgen
      seem to correlate with the aging of the SNB system.

PMID- 9535106
TI  - Elevated extracellular glutamate concentrations increased malondialdehyde
      production in anesthetized rat brain cortex.
AB  - Oxidative stress is believed to be involved in the damaging mechanism of
      excitotoxic insult. Thus, we investigated the effect of elevated extracellular
      glutamate levels on malondialdehyde production, a common index of lipid
      peroxidation, in anesthetized rat brain cortex. Elevation of extracellular
      glutamate levels was achieved either by exogenously perfusing glutamate
      solutions, or by perfusing L-trans-pyrrolidine-2,4-dicarboxylate (PDC), a
      competitive inhibitor of glutamate uptake transporter, through an implanted
      microdialysis probe. Malondialdehyde levels in the microdialysates, which were
      reacted with thiobarbituric acid, were analyzed by a high performance liquid
      chromatography system equipped with a fluorescence detector. Perfusion of
      glutamate (1.5 and 15 mM) resulted in dose-dependent increases in extracellular
      malondialdehyde production (as high as a 6-fold increase in malondialdehyde
      production following perfusion of 15 mM glutamate solution). PDC (3.14 and 31.4
      mM), not only significantly increased the extracellular glutamate levels in a
      dose-dependent manner, but also dramatically increased malondialdehyde production
      (as high as 20-fold increase). These results suggest that excitotoxicity induces
      oxidative stress in anesthetized rat brain cortex, as evidenced by the glutamate
      induced increase in malondialdehyde production.

PMID- 9535107
TI  - Age-related changes in D1 and D2 receptor mRNA expression in postmortem human
      putamen with and without multiple small infarcts.
AB  - Expression of messenger RNAs (mRNAs) encoding the D1 and D2 dopamine receptors as
      a function of age was determined in the human putamen using the reverse
      transcription-polymerase chain reaction (RT-PCR). In cases without multiple small
      infarcts (status lacunaris) in the putamen, D1 mRNA expression was unaltered,
      while D2 mRNA expression significantly decreased with age. Both D1 and D2 mRNA
      expression was lower in cases with status lacunaris. The reduction in D1
      receptors primarily located on striatonigral neurons or D2 receptors primarily
      located on striatopallidal neurons may inhibit thalamocortical neurons. The
      decreased transcription of D1 and D2 receptor genes may in part account for
      increased susceptibility to hypokinetic disorders in the elderly.

PMID- 9535109
TI  - Nitrergic innervation of the cat liver.
AB  - The aim of this work was to study the nitrergic innervation in the liver of the
      cat using immunocytochemical procedures. At the hepatic hilus, a rich plexus of
      neuronal nitric oxide synthase immunoreactive (nNOS-IR) nerve fibers and ganglia
      was detected around the interlobular branch of the bile duct. nNOS-IR nerve
      fibers were observed running with the components of the intralobular portal
      triads located close to the hepatic hilus, as well as with a few vessels and
      ducts of the deeper parenchyma. These latter fibers, beside others located in
      Glisson's capsule, occasionally showed short ramifications entering the
      parenchyma itself. The present results suggest that, in the cat liver, nNOS is
      involved in the autonomic control of hepatic blood flow, with a limited role in
      the regulation of hepatobiliary excretory activity and hepatocellular metabolic
      function.

PMID- 9535108
TI  - Immunohistochemical localization of leptin receptor in the rat brain.
AB  - The distribution of leptin receptor in the rat brain was determined by
      immunocytochemistry and Western blotting. Strong leptin receptor immunoreactivity
      was detected in the arcuate, paraventricular and ventromedial nuclei of the
      hypothalamus, and lateral hypothalamic area. The olfactory bulb, neocortex,
      cerebellar cortex, dorsal raphe nucleus, inferior olive nucleus, nucleus of the
      solitary tract, dorsal motor nucleus of the vagus nerve also showed intense
      immunoreactivity. Western blotting analysis yielded a 120-kDa major band.

PMID- 9535110
TI  - Effects of near-ultraviolet light on the nocturnal serotonin N-acetyltransferase
      activity of rat pineal gland.
AB  - Effects of near-ultraviolet (UV-A; 325-390 nm, peak at 365 nm) light on the
      activity of the pineal serotonin N-acetyltransferase (NAT; a penultimate and key
      regulatory enzyme in melatonin biosynthesis) were examined in rats. Acute
      exposure of dark-adapted animals to UV-A radiation produced a marked suppression
      of NAT activity of the pineal gland, the effect being dependent on exposure time.
      The decrease in the night-time NAT activity evoked by a 1-min pulse of UV-A light
      (as well as by a 15-s pulse of broad-band visible light) gradually deepened
      during the first 40 min of treatment of animals with constant darkness, then the
      enzyme activity began to rise reaching control values by 3 h. Treatment of rats
      with a protein synthesis inhibitor, cycloheximide, attenuated this night-driven
      reactivation of the pineal NAT activity. The presented results provide evidence
      that UV-A light is a powerful signal capable of controlling melatonin
      biosynthesis in rat pineal gland.

PMID- 9535111
TI  - Serotonergic neurons are present and innervate blood vessels in the olfactory
      bulb of the laboratory shrew, Suncus murinus.
AB  - The distribution and characteristics of serotonin-immunoreactivity in the
      olfactory bulb of the laboratory shrew (Suncus murinus, insectivore) was studied
      immunohistochemically. Serotonergic neurons were found only in the subependymal
      layer of the main olfactory bulb. These neurons were 8-12 microm in size and
      bipolar in shape. These serotonergic neurons had smooth nerve fibers which
      innervate blood vessels located mainly in the subependymal layer of the main
      olfactory bulb. On the other hand, other serotonergic nerve fibers with
      varicosities, which must be extrinsic, were detected in most olfactory layers
      except the olfactory nerve layer. This result suggests that intrinsic
      serotonergic neurons may control blood vessels and varicose serotonergic nerve
      fibers may act to modulate the olfactory transmission.

PMID- 9535112
TI  - Postischemic hyperthermia increases expression of hsp72 mRNA after brief ischemia
      in the gerbil.
AB  - Brain temperature during ischemia critically determines insult severity, and
      temperature changes during recirculation may also affect subsequent injury. We
      have examined the impact of postischemic temperature on induction of the 70 kDa
      stress protein, hsp72, after brief ischemia in the gerbil. Animals were subjected
      to 2 min ischemia after which they were maintained under continuous halothane
      anesthesia during 3 h recirculation, and were either kept normothermic or
      subjected to hyperthermia comparable to that which occurs spontaneously in
      gerbils released from anesthesia immediately after the occlusion. Quantitative in
      situ hybridization showed striking dependence of hsp72 induction on postischemic
      hyperthermia. This result establishes that delayed temperature-sensitive signals
      mediate this injury-associated transcriptional response, and demonstrates that
      postischemic temperature must be carefully monitored in studies of gene
      expression and induced tolerance employing brief ischemic insults.

PMID- 9535113
TI  - Changes in the morphology of sympathetic preganglionic neurons parallel the
      development of autonomic dysreflexia after spinal cord injury in rats.
AB  - Following spinal cord transection (SCT), sensory input to the spinal cord causes
      increases in arterial pressure that are small in rats 1 week after SCT, but
      become large and well established by 2 weeks. Moreover, sympathetic preganglionic
      neurons (SPNs) undergo atrophy by 1 week after SCT, and regeneration of these
      neurons may be an important factor in the etiology of this autonomic dysreflexia.
      Therefore, we examined the morphology of SPNs 2 weeks after SCT using retrograde
      transport of the cholera toxin subunit B. The dendritic arbors of SPNs were re
      established by 2 weeks after SCT. This regeneration parallels the time course of
      the development of autonomic dysreflexia after cord injury in the rat, and may
      play a role in initiating this disorder.

PMID- 9535114
TI  - Chronic morphine alters calbindin D-28k immunostaining patterns in mouse
      forebrain.
AB  - The influence of chronic morphine treatment on the brain of adult mouse has been
      studied. Female Swiss mice were daily administered saline or morphine (30 or 60
      mg/kg body weight) for a period comprising 7 days before mating, during gestation
      and until 21 days post-partum. Their brains were then perfusion-fixed and
      examined for histology and calbindin D-28k protein-immunoreactivity. Histological
      observations revealed no significant changes in the various brain regions;
      whereas a reduced number of calbindin-positive cells was encountered in the
      cingulate and parietal cortices and the lateral septal regions of morphine
      treated brains compared with those of controls. The alteration in the expression
      patterns of this neuroprotective calcium-binding protein in specific regions of
      the adult brain might be one of the mechanisms by which the addictive drugs
      modify the functional aspects of the CNS.

PMID- 9535115
TI  - Calcium inflow of hamster Merkel cells in response to hyposmotic stimulation
      indicate a stretch activated ion channel.
AB  - The aim of this study was to investigate the existence of the stretch activated
      ion channels in single Merkel cell using microfluorimetric techniques. Single
      Merkel cells were dissociated enzymatically from the touch domes in the cheek
      pouch mucosa of 4-8 week old golden hamsters. They were loaded with calcium
      (Ca2+) fluorescent indicator fura-2/AM. The increase in intracellular Ca2+
      concentration ([Ca2+]i) of a single Merkel cell (quinacrine fluorescent cell) was
      induced by hyposmotic solution in normal Krebs solution, while it was not induced
      by Ca2+-free hyposmotic solution in Ca2+-free physiological solution. Gadolinium
      ion (10 microM) in normal Krebs solution partially blocked the increase in
      [Ca2+]i of Merkel cells induced by hyposmotic solution. Hence, this study
      revealed that stretch activated ion channels existed on the Merkel cell membrane.

PMID- 9535116
TI  - NO is not involved in the simvastatin induced cell division and differentiation
      in PC12 cells.
AB  - Simvastatin, a potent 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase
      inhibitor has been reported to inhibit cell division and induce neurite-like
      outgrowth in PC12 cells [Sato-Suzuki, I. and Murota, S., Neurosci. Lett., 220
      (1996) 21-24]. In the present paper, we examined whether the induced nitric oxide
      (NO) in the simvastatin-treated PC12 cells is involved in the growth arrest and
      differentiation as reported in nerve growth factor (NGF) treated PC12 cells.
      Treatment of PC12 cells with simvastatin caused peripherin formation and enhanced
      NO production just like NGF-treated PC12 cells. Different from NGF, however, NO
      synthase inhibitors could not affect the growth arrest and differentiation in
      simvastatin-treated PC12 cells. In conclusion, NO had nothing to do with cell
      division and differentiation in simvastatin-treated PC12 cells.

PMID- 9535117
TI  - Opposing regulation of tau protein levels by ionotropic and metabotropic
      glutamate receptors in human NT2 neurons.
AB  - Human NT2-N neurons derived from retinoic acid treatment of the NTera 2 cell line
      were used to determine the consequences of ionotropic glutamate receptor (iGluR)
      hyperstimulation and possible modulatory role(s) exerted by metabotropic
      glutamate receptor (mGluR) activation. We found that NT2-N neurons express the
      NR1 subunit of N-methyl-D-aspartate (NMDA) iGluRs and mRNA encoding the 1a
      isoform of mGluRs. A 15 min pulse with 100 microM NMDA induced an increase in the
      levels of tau proteins in NT2-N cells. This effect was prevented by incubating
      NT2-N neurons in the presence of the mGluR agonist (1 S,3R)-1-aminocyclopentane
      1,3-dicarboxylic acid (1S,3R-ACPD). This phenomenon was related, in terms of
      doses and time, with the observed 1S,3R-ACPD-mediated protection against NMDA
      induced NT2-N cell death. Our findings suggest that iGluRs and mGluRs might
      participate in the control of human neuron viability by differentially affecting
      the expression of tau proteins.

PMID- 9535118
TI  - Mediation of the cardiovascular response of adenosine A1 receptor through a
      GABA(B) receptor in the spinal cord of the rat.
AB  - Cardiovascular inhibitory effects induced by intrathecal (i.t.) administration of
      adenosine A1 receptor agonist and its modulation by cyclic AMP was suggested by
      our previous report. In this experiment, we examined the mediation of
      cardiovascular effects of adenosine A1 receptor by gamma-aminobutyric acid
      receptors A and B [GABA(A) and GABA(B)] in the spinal cord. I.t. administration
      of 10 nmol of N6-cyclohexyladenosine (CHA), an adenosine A1 receptor agonist, and
      pretreatment with bicuculline (10 nmol, i.t), a GABA(A) receptor antagonist, and
      5-aminovaleric acid (50 nmol, i.t.), a GABA(B) receptor antagonist, prior to
      injection of CHA were performed in anesthetized, artificially ventilated Sprague
      Dawley rats. I.t. injection of 50 nmol of 5-aminovaleric acid significantly
      attenuated the inhibitory cardiovascular effects of CHA but 10 nmol of
      bicuculline did not alter CHA-induced cardiovascular actions. It is suggested
      that cardiovascular responses of adenosine A1 receptor is mediated by GABA(B)
      receptor in the spinal cord.

PMID- 9535119
TI  - Destruction of locus coeruleus neuronal perikarya after injection of anti
      dopamine-B-hydroxylase immunotoxin into the olfactory bulb of the rat.
AB  - Saporin, a ribosome-inactivating protein, was coupled to a monoclonal antibody to
      dopamine-B-hydroxylase (DBH) and injected unilaterally into the olfactory bulb of
      rats. After 4-13 days survival, the rat brain was processed histologically and
      the locus coerulei (LC) examined with Nissl and anti-DBH staining. There were
      degenerating dendrites in surviving LC neurons on the side ipsilateral to the
      immunotoxin-injected olfactory bulb. The number of Nissl-positive LC neurons in a
      transverse section through the caudal one third of the LC was reduced from 116+/
      10 to 50+/-8 neurons (P < 0.01, n = 7) and the number of DBH-positive neurons in
      the more rostral LC sections was reduced from 13+/-2 to 5+/-1 (P < 0.05, n = 4).
      Our results indicate that it is possible to lesion LC neurons via retrograde
      intraaxonal transport of saporin-anti-DBH immunotoxin from the olfactory bulb.

PMID- 9535120
TI  - Intrathecal administration of the adenosine A1 receptor agonist R-phenylisopropyl
      adenosine reduces presumed pain behaviour in a rat model of central pain.
AB  - Effects of intrathecally (i.t.) administered R-phenylisopropyl adenosine (R-PIA),
      an adenosine A1 receptor agonist, on presumed pain behaviour were assessed in a
      rat model of chronic central pain. Spinal cord injury was induced photochemically
      via laser irradiation of the spinal cord after intravenous injection of
      erythrosin B in rats. The chronic allodynia-like behaviour that developed in some
      animals was studied. R-PIA (3 and 10 nmol), injected i.t. reduced the mechanical
      and cold allodynia-like symptoms as tested with von Frey filaments and ethyl
      chloride spray, respectively. No side effects were observed. The effect of R-PIA
      was significant for up to 5 h and was reversed by theophylline, an adenosine
      receptor antagonist.

PMID- 9535121
TI  - Abstraction is impaired at the perceptual level in schizophrenic patients.
AB  - This study investigates category learning in schizophrenia in order to evaluate
      abstraction abilities at the perceptual level. The participants learned about two
      categories of geometric shapes. The category exemplars were presented
      successively. In the case of schizophrenic patients, longer exposure time and
      more stimulus presentations were used to counterbalance attention impairments. In
      spite of this, the perceptual category learning was significantly impaired in the
      patient group. In contrast, when the training procedure involved verbal category
      definition and not perceptual learning, the performance of schizophrenics was
      similar to that of the healthy controls. These findings suggest that the
      perceptual learning of categories, but not free classification judgements are
      impaired in schizophrenia, and that this impairment is not due to pure
      attentional disturbances.

PMID- 9535122
TI  - Expression of Kin, a nuclear protein binding to curved DNA, in mammal and avian
      brains.
AB  - Kin is a nuclear protein which presents cross-immunoreactivity with the bacterial
      RecA protein and which efficiently binds to curved DNA. This genomic interaction
      could be implied in DNA repair and illegitimate recombination in eukaryotic
      cells. Using immunocytochemistry with anti-RecA antibodies, we report the
      ubiquitous presence of the Kin protein in the CNS of mice and quails. However,
      some brain structures such as the hippocampal area, the locus coeruleus and
      Purkinje cells are preferentially immunolabelled and show some homologies between
      the two species. In conclusion, the expression of the Kin protein is preserved in
      the phylogeny of the brain of higher vertebrates.

PMID- 9535125
TI  - Association study of a functional catechol-O-methyltransferase gene polymorphism
      in Japanese schizophrenics.
AB  - Catechol-O-methyltransferase (COMT) is an enzyme which inactivates catecholamine
      neurotransmitters by methylation, and is considered a candidate for involvement
      in schizophrenia. A functional COMT gene polymorphism influencing the enzyme
      activities, the high activity (val-108) and the low activity allele (met-108),
      was recently confirmed. We investigated a genetic association between
      schizophrenia and the COMT gene polymorphism in 150 Japanese schizophrenics and
      controls. We detected the low activity met-108 allele more frequently in
      schizophrenics than in the controls, and found that subjects sharing the met-108
      allele (val/met and met/met) are significantly more common in the patients than
      in the controls. The results suggest that the low activity met-108 allele may be
      involved in susceptibility for schizophrenia.

PMID- 9535123
TI  - Evidence for an inhibition by endogenous galanin of neurogenic cutaneous
      vasodilatation in the pigeon.
AB  - The effect of high affinity galanin antagonist M35 on neurogenic cutaneous
      vasodilatation has been studied in the pigeon using a Laser Doppler Imager.
      Cutaneous application of mustard oil or antidromic electrical stimulation of a
      cutaneous nerve produced a small increase in skin blood flow. Close arterial
      injection of M35 prior to chemical or electrical stimulation resulted in a marked
      augmentation of the vasodilatory response. This effect was abolished by chronic
      denervation. The results suggest a nerve-mediated inhibitory effect of endogenous
      galanin on neurogenic cutaneous vasodilatation in the pigeon skin and provide the
      first experimental evidence for an inhibitory local regulatory function of
      cutaneous sensory nerves at least in the avian skin.

PMID- 9535124
TI  - Central NO is involved in the antinociceptive action of intracisternal
      antidepressants in freely moving rats.
AB  - The present study was performed to examine the central effects of antidepressants
      on nociceptive jaw opening reflex after intracisternal injection. we also
      investigated the mechanisms of central antinociceptive action of intracisternal
      antidepressants. We recorded the jaw opening reflex in freely moving rats and
      chose to administer antidepressants intracisternally in order to eliminate the
      effects of anesthetic agents on the pain assessment and evaluate the importance
      of the spinal site of action of antidepressants. After intracisternal injection
      of 15 microg imipramine, digastric electromyogram (dEMG) was decreased to 76+/-6%
      of the control. Intracisternal administration of 30 microg desipramine,
      nortriptyline or imipramine suppressed dEMG remarkably to 48+/-2, 27+/-8, or 25+/
      5% of the control, respectively. The suppression of dEMG was maintained for 50
      min. L-NG-Nitroarginine methyl ester (NAME) blocked the suppression of dEMG from
      32+/-2 to 81+/-5% of the control. These results indicate that antidepressants
      produce antinociception through central mechanisms in the orofacial area. The
      central NO pathway seems to be involved in the antinociception of intracisternal
      antidepressants at supraspinal sites.

PMID- 9535126
TI  - Information transmission at 500 bits/s by action potentials in a mechanosensory
      neuron of the cockroach.
AB  - Action potentials are widely used to transmit information within nervous systems
      but information encoding and transmission rates by action potentials are poorly
      understood. In the absence of knowledge about encoding, most previous work has
      used signal-to-noise ratios to estimate information capacities. We used a
      mechanosensory neuron to transmit information by a simple encoding scheme that
      allowed us to measure the transmission rate directly. Using either mechanical or
      electrical stimulation, information was transmitted at rates up to 500 bits/s,
      higher than ever reported before for real action potentials. However, the maximum
      possible message length decreased strongly with transmission rate, from
      approximately infinite at 100 bits/s to approximately 100 ms at 500 bits/ s,
      probably due to ionic adaptation processes within the neuronal membrane.

PMID- 9535127
TI  - A study of cell death in Werdnig Hoffmann disease brain.
AB  - We examined the occurrence of apoptotic cell death in the autopsied brains of
      four patients with Werdnig Hoffmann disease (WH), using TdT-mediated DIG-dUTP
      nick end labeling (TUNEL) and immunohistochemistry for apoptosis-related
      proteins. Three of the four patients, aged over 6 months, exhibited TUNEL
      positive cells in the lateral nuclei of the thalamus, and one of the three
      patients also had TUNEL-positive cells in the cerebral cortex. The labeled nuclei
      did not show characteristic features such as nuclear fragmentation or apoptotic
      bodies, and synaptophysin-positive granules were observed around some of the
      TUNEL-positive cells, although none of the antibodies against glial markers could
      visualize TUNEL-positive cells. TUNEL-positive cells were not observed in other
      regions examined, including the spinal cord, medulla and cerebellum or in the
      brains of three age-matched controls. There were neither immunopositive
      structures for bcl-2 or p53 nor alteration of in situ expression of bcl-xs/l or
      bax in any subject, and the TUNEL-positive cells lacked immunopositivity against
      apoptosis-related proteins. The presence of these TUNEL-positive cells might
      suggest latent neurodegeneration in the thalamus before central chromatolysis of
      neurons or neuronal loss appears, although it is not clear whether apoptotic cell
      death is involved in this degenerative process.

PMID- 9535128
TI  - Beta-amyloid peptide 25-35 regulates basal and hormone-stimulated Ca2+ levels in
      cultured rat astrocytes.
AB  - Beta-amyloid peptide (beta-AP), a characteristic constituent found in senile
      plaques characteristic for Alzheimer's disease, is neurotoxic by a still largely
      unknown mechanism. The fragment beta-AP 25-35 induces the full neurotoxic
      effects. It is important to understand for neurons and astrocytes the influence
      of beta-AP on Ca2+, a key regulator in cell toxicity and cell damage. Here we
      examined the effects of acute application of beta-A4 and beta-AP 25-35 on the
      regulation of cytosolic Ca2+ ([Ca2+]i) in rat astrocytes in primary culture.
      Transient [Ca2+]i rise in astrocytes induced by a brief stimulation with beta-AP
      was most probably due to release of Ca2+ from intracellular stores which was
      exacerbated by reduced extracellular Ca2+ indicating the involvement of receptors
      sensing extracellular Ca2+. Furthermore, P2 receptor-induced [Ca2+]i oscillations
      in astrocytes were reversibly interrupted by beta-AP.

PMID- 9535129
TI  - Autotomy in rats following peripheral nerve transection is attenuated by
      preceding formalin injections into the same limb.
AB  - The influence of an evolving painful inflammatory lesion on the development of
      autotomy, a behavioural model of denervation pain, was studied in rats suffering
      sciatic and saphenous nerves transection 30 or 60 min, and 1, 3, 7 or 14 days
      after being injected with formalin (50 microl, 5%, s.c). Hindpaws pressure and
      heat nociceptive thresholds and volume of the injected paw were assessed, in non
      operated rats, at the above time-points. The main effects on autotomy were: (1) a
      significant attenuation when formalin injection preceded the neurectomies by 1
      day or more, a period characterized by hypalgesia of the injected paw to both
      mechanical (during the first week) and thermal (spanning up to the third day
      after formalin) stimuli and inflammation (lasting for 14 days); (2) a
      significantly earlier onset when formalin was injected 30 min before
      neurectomies. Possible mechanisms linking nociceptive responsiveness and
      inflammation to the development of autotomy are discussed.

PMID- 9535130
TI  - A dopamine-synthesizing cell group demonstrated in the human basal forebrain by
      dual labeling immunohistochemical technique of tyrosine hydroxylase and aromatic
      L-amino acid decarboxylase.
AB  - The human basal forebrain has been known to contain many neurons immunoreactive
      (ir) to tyrosine hydroxylase (TH; the first dopamine-synthesizing enzyme). We
      examined whether these neurons might contain aromatic L-amino acid decarboxylase
      (AADC; the second step dopamine-synthesizing enzyme) by dual labeling
      immunohistochemistry and confocal laser-scanning microscopy. Neurons dually
      labeled for TH and AADC were found in the anterior olfactory nucleus, olfactory
      tubercle and the ventral margin of the rostral nucleus accumbens. The examination
      in the basal forebrain of the macaque monkey also gave substantially the same
      results. These neurons appear to constitute an independent dopaminergic cell
      group in the primate basal forebrain.

PMID- 9535131
TI  - Cerebellar neurodegeneration in human hereditary DNA repair disorders.
AB  - Recent findings have focused attention on the role of apoptosis in
      neurodegenerative diseases, however, the apoptotic process in child-onset brain
      disorders has been little investigated. Xeroderma pigmentosum (XP) and Cockayne
      syndrome (CS) are hereditary disorders characterized by impaired DNA repair and
      neurodegeneration. We investigated apoptotic cell death in the cerebellum of five
      cases of XP group A (XPA), four cases of CS, and twelve controls, using TdT
      mediated DIG-dUTP nick-end labeling (TUNEL) and immunohistochemical staining for
      bcl-2, bcl-x, p53, bax, BDNF and Trk B. The TUNEL-positive cells were found in
      the granule cells of the cerebellar cortex of two patients with XPA and two
      patients with CS, whereas such cells were not detected in the cerebellar cortex
      in controls. Upregulation of bcl-2 or BDNF was not observed, and bcl-x expression
      was not altered. Some patients showed nuclear expression of p53 in the granule
      cells and/or molecular layer, bax-positive glial cells in the cerebellar white
      matter, and a few Trk B-positive cells in the granular layer. These findings
      suggest that apoptotic cell death can be involved in the cerebellar degeneration
      in patients with hereditary defects in DNA repair mechanisms.

PMID- 9535132
TI  - Cloning and expression of the programmed cell death regulator Bad in the rat
      brain.
AB  - The Bcl-2 family of proteins consists of both antagonists (e.g. Bcl-2) and
      agonists (e.g. Bax) that regulate apoptosis and compete through dimerization. In
      the present study we cloned the cDNA encoding the rat brain BAD, a distant member
      of the Bcl-2 family that was shown to promote cell death. The cloned cDNA encoded
      a protein of 205 amino acids, containing three putative Bcl-2 homology domains
      (BH1, BH2 and BH3) and no C-terminal signal-anchor sequence. The predicted amino
      acid sequence was identical to the Bad-cDNA recently cloned from the rat ovary
      with the exception of a stretch of six amino acids, thus indicating the existence
      of two Bad alternative splice variants or a sequence artifact in the rat ovary
      Bad-cDNA. Immunohistochemical analysis in the rat brain revealed the exclusive
      expression of Bad in the epithelial cells of the choroid plexus, a result which
      is consistent with a very specialized function of Bad in the brain.

PMID- 9535133
TI  - Thapsigargin inhibits bicuculline-induced epileptiform excitability in rat
      hippocampal slices.
AB  - Evoked field potentials were recorded in the CA3 region of rat hippocampal slices
      to detect whether intracellular Ca2+ stores are involved in the epileptiform
      effects of the two prototypic GABA(A) antagonists, bicuculline methiodide (BMI)
      and gabazine (SR-95531; GBZ). Field population spikes gradually increased and
      became repetitive (epileptiform bursting) in the presence of either BMI (5
      microM), or GBZ (5 microM). Thapsigargin (2 microM), a depletor of intracellular
      Ca2+ stores, reduced the epileptiform effect of BMI, but had no significant
      effect on the GBZ-induced hyperexcitability. These data suggest that Ca2+ release
      from intracellular stores participates in the epileptiform response of
      hippocampal CA3 neurons to BMI, but not in the response to GBZ.

PMID- 9535134
TI  - An electrophysiological study on the autonomic innervation of the mesenteric
      lymph node in the rat.
AB  - Splanchnic innervation of the mesenteric lymph node was studied by means of
      electrophysiological technique in the rat. The effect of intravenous (i.v.)
      injection of recombinant human interleukin-1beta (rhIL-1beta) on the activity of
      efferent nerve fibers innervating the mesenteric lymph node was observed in the
      urethane anesthetized rat. An i.v. injection of 10 ng rhIL-1beta caused a gradual
      increase in efferent activity which lasted longer than 90 min. Dose related
      responses were observed at doses of 1, 10 and 100 ng. The least effective dose
      was about 10 ng. The conduction velocities estimated in mesenteric nerve fibers
      to the lymph node distributed in the range of 1.9-0.9 m/s, and the mean velocity
      was 1.39+/-0.34 m/s (n = 5). These observations implicate the involvement in the
      neural modulation of immune function of the mesenteric lymph node.

PMID- 9535135
TI  - Corticospinal excitability modulation during mental simulation of wrist movements
      in human subjects.
AB  - Motor evoked potentials (MEPs) to magnetic transcranial stimulation (TCS) were
      simultaneously and bilaterally recorded from flexor carpi radialis (FCR) and
      extensor communis digitorum (ECD) muscles in seven healthy and trained subjects.
      Latencies and amplitudes characteristics of MEPs were investigated under the
      following randomised conditions: muscular and mental relaxation; mental
      simulation, during absolute muscular relaxation, selective flexion or extension
      of the right or left wrist muscles; arithmetical calculation with muscular
      relaxation. Unspecific, diffuse facilitatory effects on MEPs amplitude were
      induced by mental non motor activity (arithmetical calculation). A further
      specific and lateralised amplitude potentiation on the agonist muscle acting as
      'prime mover' for the mentally simulated movement was consistently found in all
      the subjects, without significant latency changes. Inhibitory effects on
      antagonists were evident only in two subjects.

PMID- 9535136
TI  - Activation of non-NMDA receptors stimulates acetylcholine and GABA release from
      dorsal hippocampus: a microdialysis study in the rat.
AB  - The effect of the non-N-methyl-D-aspartate (NMDA) agonists (RS)-alpha-amino-3
      hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and quisqualate (QUIS) on the
      release of acetylcholine (ACh), gamma-amino butyric acid (GABA), aspartate (Asp)
      and glutamate (Glu) from the hippocampus of freely moving rats was studied by
      transversal microdialysis. Intracerebroventricular (i.c.v.) administration of the
      non-NMDA receptor agonist AMPA (0.5 nmol) enhanced (by about 200%) ACh release
      from the hippocampus. The effect of AMPA was completely antagonized by 6-nitro-7
      sulphamoyl-benz(f)quinoxaline-2,3-dione (NBQX; 2 nmol, i.c.v). No effect was seen
      when AMPA was perfused through the septum. However, AMPA (200 microM) locally
      applied to the hippocampus, increased (by about 200%) ACh release. QUIS (200
      microM) applied locally to the hippocampus produced a long-lasting increase in
      the release of ACh (by about 215%) and GABA (by about 460%). Local infusion of
      tetrodotoxin (1 microM) decreased ACh and GABA basal extracellular levels, and
      abolished the QUIS-induced increase in ACh and GABA. Our results demonstrate that
      non-NMDA glutamatergic receptors in the hippocampus regulate hippocampal release
      of GABA and ACh.

PMID- 9535137
TI  - Searching for information from unreported trials--amnesty for the past and
      prospective meta-analyses for the future.

PMID- 9535138
TI  - Protocol for prospective collaborative overviews of major randomized trials of
      blood-pressure-lowering treatments. World Health Organization-International
      Society of Hypertension Blood Pressure Lowering Treatment Trialists'
      Collaboration.
AB  - OBJECTIVE: To conduct prospectively planned overviews (meta-analyses) of the
      ongoing randomized trials of blood-pressure-lowering drugs. These overviews
      should provide reliable data about the effects of newer classes of blood-pressure
      lowering drugs (such as angiotensin converting enzyme inhibitors and calcium
      antagonists) on major causes of cardiovascular mortality and morbidity for a
      variety of patient groups. METHODS: A registry of major ongoing or planned
      randomized trials (with more than 1000 patient-years of follow-up for each
      randomized group) of blood-pressure-lowering agents has been established. The
      principal investigators of each of these studies have been invited to collaborate
      in the project and to provide, upon completion of the study, a limited data set
      for inclusion in the overview analyses. The principal comparisons will be of
      newer versus older classes of blood-pressure-lowering drugs in treating patients
      with hypertension and of newer blood-pressure-lowering treatments versus
      untreated or less treated control conditions for a variety of other groups of
      patients with a high risk of cardiovascular events. Separate analyses will be
      conducted for the main drug classes and for major subgroups of patients defined
      by characteristics such as age, gender, blood pressure, diabetes, and history of
      renal disease, coronary heart disease or cerebrovascular disease. The principal
      study outcomes are stroke, major coronary heart disease events, heart failure,
      total cardiovascular deaths, total cardiovascular events and total mortality.
      RESULTS: In total 36 trials of blood-pressure-lowering treatments potentially
      eligible for inclusion in this project have been identified and agreement to
      collaborate has been confirmed by the investigators in 30 trials, with
      collaboration pending for six recently identified studies. The first round of
      analyses will be conducted in 1999 and will be based on total cardiovascular
      events observed among a total of about 64,000 patients, involving about 240,000
      patient-years of follow-up. The second round of analyses will be conducted in
      2003 on data from at least 195,000 patients and 899,000 patient-years of follow
      up. By that time it is estimated that a total of about 8000 strokes, 12,000
      coronary heart disease events and 23,000 cardiovascular events in total will have
      occurred. This should provide good statistical power to detect even modest cause
      specific differences in the incidence of the main study outcomes. CONCLUSIONS:
      The combination of trial results in prospectively planned, systematic overviews
      both reduces random errors and avoids biases. As a consequence, this project
      should provide more reliable information about the effects of newer blood
      pressure-lowering drugs than would any one study alone. The use of data from
      individual patients in these overviews will facilitate investigation of the
      separate effects of various drug regimens in treating members of major patient
      subgroups.

PMID- 9535139
TI  - Genetic analysis of the SA and Na+/K+-ATPase alpha1 genes in the Milan
      hypertensive rat.
AB  - OBJECTIVE: To study whether the SA gene locus (on rat chromosome 1) and the
      sodium potassium ATPase alpha1 gene locus (on rat chromosome 2) contribute to the
      elevated blood pressure in the Milan hypertensive rat. DESIGN: Co-segregation
      analysis using polymorphisms in the SA and Na+/K+-ATPase alpha1 genes in F2 rats
      from a cross of Milan hypertensive and Milan normotensive rats. Analysis of SA
      and N+/K+-ATPase alpha1 gene expression in kidneys of 6 and 25 weeks old Milan
      hypertensive and normotensive rats. METHODS: Genotyping of F2 rat DNA by
      restriction digestion and Southern blotting and comparison of messenger RNA
      levels by northern blot analysis. RESULTS: Renal expression of SA was
      considerably higher in normotensive than it was in hypertensive rats aged 6 and
      25 weeks. Despite this difference the SA genotype did not co-segregate with blood
      pressure, although the Milan hypertensive rat allele did co-segregate with
      greater body weight (P = 0.0014) for male F2 rats. Expression of Na+/K+-ATPase
      alpha1 was higher in the kidneys of young hypertensive rats than it was in those
      of normotensive rats and did not decline with age as occurred in the normotensive
      rats. However, again the Na+/K+-ATPase alpha1 genotype did not co-segregate with
      blood pressure. CONCLUSIONS: Despite differences in the patterns of expression of
      SA and Na+/K+-ATPase alpha1 genes in the kidneys of Milan hypertensive and
      normotensive rats, we found no evidence of co-segregation of either gene with
      blood pressure. Our results suggest that either SA is simply acting as marker for
      a linked gene in other crosses for which co-segregation with blood pressure has
      been observed, or at least, the level of its renal expression is not the sole
      determinant of its effect on blood pressure. The failure of the Na+/K+-ATPase
      alpha1 gene to co-segregate with blood pressure suggests that its greater
      expression in the kidney of the Milan hypertensive rat is either reactive or
      controlled by other genetic loci.

PMID- 9535140
TI  - Evidence that human endothelial cells express different isoforms of Na,K-ATPase.
AB  - BACKGROUND: The catalytic alpha and smaller beta subunits of the plasma membrane
      Na,K-ATPase occur in various molecular forms (alpha1, alpha2, alpha3, beta1 and
      beta2). The alpha isoforms of the enzyme have varying affinities for ouabain and
      exist in different tissues with particular distribution patterns. OBJECTIVE: To
      document the existence of isoforms of the Na,K-ATPase in cultured human umbilical
      vein endothelial cells. METHODS: Microsomal fractions were prepared by
      differential ultracentrifugation from primary cultures of human umbilical vein
      endothelial cells and from such cells obtained after three passages. Na,K-ATPase
      activity was assayed using the coupled assay method and sensitivity to ouabain
      was determined in the presence of varying concentrations of ouabain. Specific
      antibodies for the various Na,K-ATPase isoforms were used to label these
      different proteins by immunocytochemistry in endothelial cells and by Western
      blotting in isolated membranes. RESULTS: In plotting the dose-response curves for
      Na,K-ATPase activity in response to ouabain we assumed the existence of two
      independent sites exhibiting different affinities for ouabain (in the micromol/l
      and the nmol/l ranges). The contribution of low-affinity sites was threefold that
      of high-affinity sites. After three passages in culture, a specific increase in
      Na,K-ATPase activity of the high-affinity sites was observed compared with that
      of cells from primary cultures. Confocal microscopy revealed the existence of
      beta1, beta2, and alpha1 subunit proteins in human umbilical endothelial cells.
      Staining for alpha3 isoform was less pronounced and no obvious alpha2 was
      detected. CONCLUSION: These findings suggest that human umbilical vein
      endothelial cells contain beta1, beta2, a large amount of alpha1 isoform with an
      apparently low affinity for ouabain, and a lesser amount of high-affinity sites,
      which may correspond to the alpha3 protein.

PMID- 9535142
TI  - Preclinical changes of extracoronary arterial structures as indicators of
      coronary atherosclerosis in men.
AB  - BACKGROUND: Carotid artery structure change was associated with coronary artery
      stenosis by angiography of subjects who were for the most part symptomatic.
      OBJECTIVE: To determine whether structural changes at multiple extracoronary
      sites were associated with noninvasively detected coronary calcium for 94
      asymptomatic high-risk men. METHODS AND RESULTS: B-mode ultrasonography allowed
      us to detect plaque at three sites (carotid, femoral, and abdominal aorta) and to
      measure intima-medial thickness both in common carotid and in femoral arteries.
      Ultrafast computed tomography determined the presence and amount of coronary
      calcification. After adjustment for age, plaques at two or three sites were
      associated with extensive amounts of coronary calcium [odds ratio 4.94 (95%
      confidence interval 1.08-23)], but not with the presence of coronary calcium;
      increase in carotid intima-medial thickness was not associated with presence and
      extent of coronary calcium; and increase in femoral intima-medial thickness was
      associated with presence of coronary calcium [odds ratio 1.44 (95% confidence
      interval 1.03-2)] and extensive coronary calcium [odds ratio 1.50 (95% confidence
      interval 0.97-2.33)]. Adjustment for cardiovascular risk factors attenuated these
      associations. CONCLUSIONS: Femoral intima-medial thickness predicted presence of
      coronary calcium whereas femoral intima-medial thickness and overall multiple
      plaques predicted extensive coronary calcium. Because coronary calcium is a
      marker of atherosclerosis and a predictor of coronary events, B-mode
      ultrasonography could be of clinical value for stratifying coronary risk.

PMID- 9535141
TI  - Impaired vasorelaxant responses to natriuretic peptides in the stroke-prone
      phenotype of spontaneously hypertensive rats.
AB  - BACKGROUND: We have previously shown that a locus on rat chromosome 5, termed STR
      2, co-localizes with the genes encoding atrial natriuretic and brain natriuretic
      peptides, and is closely linked to the development of strokes in rats of a F2
      hybrid cohort obtained by crossing stroke-prone spontaneously hypertensive rats
      and spontaneously hypertensive rats. We also demonstrated that there are
      significant differences in vascular functioning that are co-segregated with
      stroke latency of stroke-prone spontaneously hypertensive rats. OBJECTIVE: To
      investigate the vascular responses to natriuretic peptides in the stroke-prone
      phenotype of spontaneously hypertensive rats. DESIGN AND METHODS: In view of the
      important vasoactive properties of natriuretic peptides, we tested the vascular
      responses to 10(-11)-10(-9) mol/l atrial natriuretic peptide and to 10(-11)-10(
      7) mol/l brain natriuretic peptide in isolated rings of aortas and internal
      carotid arteries obtained from stroke-prone and stroke-resistant spontaneously
      hypertensive rats. The 6-week-old rats were exposed for 4 weeks either to their
      regular diet (n = 15 of both strains) or to the stroke-permissive Japanese-style
      diet (n = 14 of both strains). A group of 14 normotensive, age-matched and sex
      matched Wistar-Kyoto rats was also studied. RESULTS: Systolic blood pressures in
      stroke-prone and stroke-resistant spontaneously hypertensive rats were similar,
      and were significantly higher than those in Wistar-Kyoto rats. Vascular responses
      to nitroglycerin, atrial natriuretic peptide, and brain natriuretic peptide in
      rats of the two hypertensive strains and in Wistar-Kyoto rats fed their regular
      diet were comparable. In contrast, the vasorelaxant responses to atrial
      natriuretic peptide in stroke-prone spontaneously hypertensive rats fed Japanese
      diet were lower both in aortas and in internal carotid arteries than were those
      in spontaneously hypertensive rats (both P < 0.05 by analysis of variance) and in
      Wistar-Kyoto rats (both P < 0.05). Similarly, vasorelaxant responses to brain
      natriuretic peptide were lower both in aortas and in internal carotid arteries of
      stroke-prone spontaneously hypertensive rats than they were in spontaneously
      hypertensive rats (both P < 0.05) and in Wistar-Kyoto rats (P < 0.05). The
      responses to nitroglycerin in the stroke-prone spontaneously hypertensive rats
      and spontaneously hypertensive rats fed Japanese-style diet were also similar.
      CONCLUSION: The vasorelaxant effects of natriuretic peptides are impaired in
      stroke-prone spontaneously hypertensive rats. This abnormality could play a role
      in the pathogenesis of stroke incidence in this hypertensive model.

PMID- 9535143
TI  - Influence of pattern of alcohol intake on blood pressure in regular drinkers: a
      controlled trial.
AB  - OBJECTIVE: To evaluate the effects of patterns of drinking (weekend versus daily
      drinking) on the pressor responses to alcohol in 55 male drinkers using clinic
      and 24 h ambulatory blood pressure monitoring. DESIGN: A randomized, controlled
      cross-over trial. METHODS: Recruitment required a regular alcohol intake of 210
      500 ml absolute alcohol/week, with > 60% consumed as beer. Fourteen subjects were
      categorized as predominantly weekend drinkers, whereas the remaining 41 subjects
      regularly drank on a daily basis. After 4 weeks of familiarization, all subjects
      were randomly allocated to drinking low-alcohol beer (0.9% vol:vol) only or to
      maintain their usual drinking habits with provision of full-strength beer (5%
      vol:vol) for 4 weeks. They then switched back to their usual drinking habits or
      low-alcohol beer, respectively, for a further 4 weeks while maintaining their
      usual drinking pattern. RESULTS: Baseline ambulatory systolic blood pressure in
      weekend but not in daily drinkers was 2.4 mmHg higher on Monday than it was on
      Thursday (P = 0.02). This Monday-Thursday difference was lost during
      intervention. When subjects switched from the high-alcohol to the low-alcohol
      period the falls in ambulatory systolic blood pressure in weekend (3.1 mmHg, P <
      0.001) and daily drinkers (2.2 mmHg, P < 0.001) were similar. Most of the fall
      was evident during week 1 of the low-alcohol period for weekend drinkers but not
      until week 4 for daily drinkers. CONCLUSION: The pressor response to alcohol
      consumption is similar in magnitude in weekend and daily drinkers, present
      throughout a 24 h period and has a rapid onset/offset in weekend drinkers but is
      more sustained in daily drinkers.

PMID- 9535144
TI  - Alcohol intake and blood pressure: the importance of time elapsed since last
      drink.
AB  - BACKGROUND: A positive association of chronic exposure to alcoholic beverages
      with blood pressure and the prevalence of hypertension has been described in
      epidemiological surveys, but the influence of time elapsed since last ingestion
      in this setting was not demonstrated. DESIGN: A cross-sectional, population-based
      survey. METHODS: In total 1089 adults from Porto Alegre, randomly selected from a
      population-based, multi-stage probability sample, were interviewed at home. The
      average daily alcohol intake of each subject was calculated taking into account
      the concentration of ethanol in the beverages (distilled or fermented beverages),
      and the time elapsed between the last ingestion of ethanol and the moment of
      blood pressure determination. Standardized sitting blood pressure and
      anthropometric parameters were collected. The magnitude and shape of the
      associations were analyzed considering blood pressure as a continuous variable
      and the prevalence of arbitrarily defined hypertension. Simple and multiple
      linear regression models, including models to identify nonlinear associations,
      with quadratic and cubic terms of the amount of alcohol consumed, were employed.
      Blood pressure means were compared by analysis of variance and analysis of
      covariance. The association between hypertension and exposure to ethanol was
      analyzed through logistic regression models, controlling for various potential
      confounders. RESULTS: Positive nonlinear associations of the amount of alcohol
      consumed with blood pressure and the prevalence of hypertension (> or = 160/95
      mmHg) were found, independent of age, years of education, smoking, and use of
      oral contraceptive and antihypertensive drugs. The consumption of 30 g/day
      ethanol was associated with increases of 1.5 and 2.3 mmHg in diastolic and
      systolic blood pressures, respectively, for men, and 2.1 and 3.2 mmHg,
      respectively, for women. The prevalence of hypertension was higher among those
      ingesting more than 30 g/day (odds ratio = 2.9, P < 0.01). The time elapsed
      between the last ingestion and blood pressure measurement was independently
      associated with the prevalence of hypertension. Men with last consumption of
      alcohol 13-23 h prior to measurement had odds of being hypertensive 2.6
      (confidence interval 1.3-5.0) greater than did subjects who had consumed
      alcoholic beverages 24 h and more before the blood pressure determination. For
      men, systolic and diastolic blood pressures were lower during the first 3 h after
      ingestion and increased afterward. Frequency of consumption and type of beverage
      consumed were not independently associated with level of blood pressure.
      CONCLUSION: A time-dependent association between alcohol consumption and effects
      on blood pressure, demonstrated in experimental studies, was found for free
      living individuals selected at random.

PMID- 9535145
TI  - The effects of voluntary running on cardiac mass and aortic compliance in Wistar
      Kyoto and spontaneously hypertensive rats.
AB  - OBJECTIVE: To investigate the effects of voluntary running exercise from 4-20
      weeks of age on aortic compliance in Wistar-Kyoto (WKY) rats and spontaneously
      hypertensive rats (SHR). DESIGN: For each species we made comparisons between
      rats housed with an exercise wheel locked (10 rats) and unlocked (10 rats).
      METHODS: Rats were killed using CO2 asphyxia and the aorta and heart of each rat
      were rapidly removed. The heart was dissected and weighed. A 4 mm descending
      proximal aortic ring was mounted on wires in an organ bath for determination of
      static compliance from the slope of the diameter-pressure relationship derived
      using Laplace's equation. RESULTS: During the final 2 weeks of training WKY rats
      ran an average of 7.9 +/- 1.0 km/24 h compared with 1.0 +/- 0.2 km/24 h for SHR.
      Body weights of WKY rats and SHR and of animals housed with locked and unlocked
      exercise wheels did not differ. The septum, left ventricle and total heart
      weights and left ventricular:body weight ratios of sedentary SHR were greater
      than those of sedentary WKY rats. Trained WKY rats had significantly higher
      atrial, left and right ventricular and total heart weights and left
      ventricular:body weight ratios than did untrained WKY rats. Aortic compliance was
      higher in trained than it was in sedentary WKY rats (12.3 +/- 0.4 versus 14.2 +/-
      0.5 microm/mmHg, P < 0.05). There was no difference between heart weights and
      aortic compliances of SHR housed with exercise wheels locked and unlocked.
      CONCLUSION: Exercise-trained WKY rats had greater intrinsic aortic compliance
      when it was measured statically in vitro, which supports results of previous
      human work revealing a blood-pressure-independent component in the elevation of
      arterial compliance with training. The lower physical activity of the SHR strain
      used in this study could contribute to their higher blood pressures and lack of
      change in aortic compliance with exercise training.

PMID- 9535146
TI  - Hemodynamic profile of corticotropin-induced hypertension in the rat.
AB  - OBJECTIVES: To examine hemodynamic variables in corticotropin-induced
      hypertension in rats and the effects of reversal of the hypertension by L
      arginine on the hemodynamic profile. METHODS: Sixty male Sprague-Dawley rats were
      randomly divided into four groups: sham treatment (0.9% NaCl, injected
      subcutaneously); 0.5 mg/kg corticotropin per day, subcutaneously; 0.6% L-arginine
      in food plus sham; and L-arginine plus corticotropin. Systolic blood pressure,
      water and food intakes, urine volume, and body weight were measured every second
      day. After 10 days mean arterial blood pressure was measured by intra-arterial
      cannulation, and cardiac output, and renal, mesenteric, and hindquarter blood
      flows were determined using transonic small animal flowmeters. RESULTS: Injection
      of corticotropin increased blood pressure, water intake, urine volume, and plasma
      sodium concentration, and decreased body weight and plasma potassium
      concentration. It increased cardiac output (P < 0.01), mesenteric blood flow (P <
      0.05), and renal vascular resistance (P < 0.05), and decreased renal blood flow
      (P < 0.05), but did not change calculated total peripheral resistance,
      hindquarter blood flow, mesenteric or hindquarter vascular resistance. L-arginine
      prevented corticotropin-induced rises in blood pressure (P < 0.001) and renal
      vascular resistance (P < 0.05), and a fall in renal blood flow (P < 0.05), but
      did not affect other hemodynamic variables. CONCLUSION: The hemodynamic profile
      of corticotropin-induced hypertension in the rat is characterized by a rise in
      cardiac output and renal vascular resistance, a fall in renal blood flow, but no
      change in total peripheral resistance, hindquarter blood flow, mesenteric
      vascular resistance, or hindquarter vascular resistance. L-arginine prevented
      corticotropin-induced rises both in blood pressure and in renal vascular
      resistance in the rat. These data suggest that the increase in renal vascular
      resistance might play a role in corticotropin-induced hypertension in the rat.

PMID- 9535147
TI  - The stress hormone adrenocorticotropin enhances sympathetic outflow to the muscle
      vascular bed in humans.
AB  - OBJECTIVE: To examine the role of adrenocorticotropin in the regulation of the
      sympathetic outflow to the muscle vascular bed in healthy female humans. DESIGN:
      Eight healthy, nonsmoking female subjects (aged 18-33 years) were examined before
      and after injection of 0.25 mg adrenocorticotropin 1-24 or placebo according to a
      balanced, double-blind cross-over protocol. METHODS: Muscle sympathetic nerve
      activity, arterial pressure, and heart rate were continuously recorded both under
      basal conditions and during a 50 min period after injection of each substance.
      Furthermore, sympathoexcitatory capacities of inspiratory apneas and cold
      pressure tests performed before and after injection of adrenocorticotropin were
      determined. RESULTS: The injection of adrenocorticotropin rapidly increased burst
      frequency of muscle sympathetic nerve activity (P < 0.01). The maximal effect of
      adrenocorticotropin, with an increase in burst frequency of 63%, occurred during
      the third minute after injection and waned subsequently, but muscle sympathetic
      nerve activity remained significantly increased during the first 10 min after
      injection. The stimulatory effect of adrenocorticotropin had disappeared 40 min
      after injection. The sympathoexcitatory capacity of a maximal inspiratory apnea
      and a cold pressure test, respectively, remained unchanged 10 and 45 min after
      the administration of adrenocorticotropin compared with control. Neither blood
      pressure nor heart rate was significantly affected by administration of the
      peptide. CONCLUSIONS: The data establish that the stress hormone
      adrenocorticotropin acutely increases sympathetic outflow to the muscle vascular
      bed in female humans. This effect is most likely mediated via central nervous
      system autonomic centers. The influence of adrenocorticotropin on the sympathetic
      nervous system might contribute to the alteration of response to stress in the
      course of the development of hypertension and could also add to the
      hypertensiogenic effects of corticosteroids and mineralocorticoids in states with
      excess adrenocorticotropin.

PMID- 9535148
TI  - Whole-blood viscosity and the insulin-resistance syndrome.
AB  - BACKGROUND: In a previous study we found that elevated blood viscosity was linked
      to the insulin resistance syndrome, and we proposed that high blood viscosity may
      increase insulin resistance. That study was based on calculated viscosity.
      OBJECTIVE: To determine whether directly measured whole-blood viscosity was
      related to the insulin-resistance syndrome in the same way as calculated
      viscosity had been found to be. METHODS: Healthy young men were examined with the
      hyperinsulinemic isoglycemic glucose clamp technique, and we related insulin
      sensitivity (glucose disposal rate) to other metabolic parameters and to blood
      viscosity. We established a technique for direct measurement of whole-blood
      viscosity. RESULTS: There were statistically significant negative correlations
      between glucose disposal rate and whole-blood viscosity at low and high shear
      rates (r = -0.41, P = 0.007 for both, n = 42). Whole-blood viscosity was
      correlated positively (n = 15) to serum triglyceride (r = 0.54, P = 0.04) and
      total cholesterol (r = 0.52, P = 0.05), and negatively with high-density
      lipoprotein cholesterol (r = -0.53, P = 0.04) concentrations. Insulin sensitivity
      index was correlated positively to high-density lipoprotein cholesterol (r =
      0.54, P = 0.04) and negatively to serum triglyceride (r = -0.69, P = 0.005) and
      to total cholesterol (r = -0.81, P = 0.0003) concentrations. CONCLUSIONS: The
      present results demonstrate for the first time that there is a negative
      relationship between directly measured whole-blood viscosity and insulin
      sensitivity as a part of the insulin-resistance syndrome. Whole-blood viscosity
      contributes to the total peripheral resistance, and these results support the
      hypothesis that insulin resistance has a hemodynamic basis.

PMID- 9535149
TI  - Insulin resistance in essential hypertension is characterized by impaired insulin
      stimulation of blood flow in skeletal muscle.
AB  - OBJECTIVE: To determine whether insulin-stimulated blood flow in patients with
      mild essential hypertension is altered. SUBJECTS: Eleven untreated mildly
      hypertensive patients [aged 35 +/- 2 years, body mass index 25.1 +/- 0.4 kg/m2,
      mean arterial pressure 110 +/- 2 mmHg (means +/- SEM) and 10 matched normotensive
      subjects (mean arterial pressure 94 +/- 3 mmHg). METHODS: Blood flow was
      quantitated directly in skeletal muscle both basally and during supraphysiologic
      hyperinsulinemia (serum insulin approximately = 450 mU/l) using radiowater
      ([15O]H2O) and positron emission tomography. Whole-body and femoral muscle
      glucose uptakes were determined using the euglycemic insulin clamp technique,
      [18F]-2-fluoro-2-deoxy-D-glucose and positron emission tomography. RESULTS: Rates
      of whole-body and femoral muscle glucose uptake were significantly lower in the
      hypertensive than in the normotensive group. Insulin increased muscle blood flow
      by 91% in the normotensive group, but only by 33% in the hypertensive group.
      CONCLUSIONS: The ability of insulin to stimulate blood flow in patients with mild
      essential hypertension is impaired.

PMID- 9535150
TI  - Predicting high blood pressure in pregnancy: a multivariate approach.
AB  - OBJECTIVE: To identify predictors of pregnancy-induced hypertension and pre
      eclampsia in 212 nulliparous women before 20 weeks' gestation and at
      approximately 28 weeks' gestation. STUDY DESIGN: A randomized, prospective study
      in a teaching hospital. We performed standardized measurements of systolic and
      diastolic arterial blood pressures, body mass index, urinary calcium:creatinine
      ratio and components of the renin-angiotensin system, including platelet
      angiotensin II binding site density. Attending clinicians were blinded to the
      results. Outcome was assessed by one observer at the end of pregnancy.
      Discriminant function analysis was used to identify significant predictors.
      RESULTS: Fifty-five women had transient, presumed 'white-coat', systolic
      hypertension at the time of first pregnancy visit; they were twice as likely to
      develop pregnancy-induced hypertension and pre-eclampsia and five times more
      likely to deliver prematurely. Body mass index, platelet angiotensin II binding
      site density and urinary calcium:creatinine ratio measured before 20 weeks
      gestation were also significant predictors. At 28 weeks of pregnancy,
      measurements of the blood pressure were significant predictors (reflecting the
      near clinical expression of the disease), together with the plasma
      angiotensinogen concentration. CONCLUSIONS: A single systolic blood pressure
      reading of 140 mmHg or more before 20 weeks' gestation indicates a higher than
      normal risk of pregnancy-induced hypertension and pre-eclampsia and premature
      delivery. Discriminator biochemical variables were also identified at this time,
      which might allow the more rational use of prophylactic measures.

PMID- 9535151
TI  - Coronary hemodynamics in aging spontaneously hypertensive and normotensive Wistar
      Kyoto rats.
AB  - OBJECTIVE: To delineate hypertension-related and age-related changes in coronary
      hemodynamics and to assess the role of myocardial (i.e. left ventricular)
      hypertrophy and cardiac fibrosis in inducing progressive deterioration of
      coronary flow reserve associated both with hypertension and with aging. METHODS:
      Systemic and coronary hemodynamics (using radionuclide-labeled microspheres),
      right ventricular, left ventricular, and aortic mass indexes, and ventricular
      hydroxyproline concentrations (an estimate of collagen) in normotensive Wistar
      Kyoto and spontaneously hypertensive rats aged 22, 35, and 65 weeks were
      determined. RESULTS: Spontaneously hypertensive rats of all ages had greater left
      ventricular and aortic masses, greater collagen concentrations in both
      ventricles, a lower coronary flow reserve, and greater minimal coronary vascular
      resistance after administration of dipyridamole than did Wistar-Kyoto rats.
      Despite spontaneously hypertensive rats having only left ventricular hypertrophy,
      coronary hemodynamics were impaired to the same extent in both ventricles.
      Progressive increases in myocardial collagen concentration, decreases in coronary
      flow reserve, and increases in minimal coronary vascular resistance were observed
      in rats of both strains with aging. A positive correlation and linear regression
      between myocardial collagen concentration and minimal vascular resistance were
      found for both ventricles of rats of both strains. CONCLUSIONS: Both aging and
      hypertension adversely affected the coronary circulation; furthermore, these
      effects appeared to be additive. Cardiac fibrosis, but not hypertrophy, might
      play a role in progressive deterioration of coronary hemodynamics in aging and
      hypertension and could provide an explanation for the diastolic dysfunction
      encountered clinically in older patients with hypertension.

PMID- 9535152
TI  - Bradykinin-induced release of nitric oxide by the isolated perfused rat heart:
      importance of preformed pools of nitric oxide-containing factors.
AB  - OBJECTIVE: To study whether the vasorelaxant effect of bradykinin in the coronary
      vascular bed depends on the release of NO from preformed pools and/or de-novo
      synthesis of NO resulting from bradykinin-induced stimulation of NO synthase.
      DESIGN AND METHODS: Rat hearts were perfused according to Langendorff's method.
      Coronary flow was measured continuously. We constructed concentration-response
      curves for bradykinin and L-arginine under control conditions, after
      downregulation of NO synthase by exposing the heart to high concentrations (10
      mmol/l) of NO and during chronic inhibition of NO synthase, obtained by perfusing
      the heart for 30 min with 0.1 mmol/l N(omega)-nitro-L-arginine methyl ester. The
      effect of acute inhibition of NO synthase was studied by infusing single
      submaximal doses of bradykinin and of L-arginine in the absence and presence of
      0.1 mmol/l N(omega)-nitro-L-arginine methyl ester. RESULTS: Coronary flow
      [baseline 9 +/- 2 ml/min (mean +/- SD)] increased to maximally 23 +/- 6 ml/min
      with bradykinin and to 16 +/- 4 ml/min with L-arginine. Maximal coronary flow,
      established as the maximal effect in response to NO, was 22 +/- 4 ml/min. Chronic
      inhibition of NO synthase reduced coronary flow to 4 +/- 1 ml/min. Coronary flow
      did not change after downregulation of NO synthase by NO. Neither downregulation
      nor acute inhibition of NO synthase affected the response to bradykinin, whereas
      chronic inhibition of NO synthase blocked the bradykinin-induced increase in
      coronary flow by > 90%. Administration of L-arginine no longer increased coronary
      flow under all tested conditions. CONCLUSIONS: Preformed pools of NO-containing
      factors exist within the isolated perfused heart and bradykinin exerts its
      vasorelaxant effects at least in part by the mobilization of these preformed
      pools. These data may reconcile previous discrepancies about the (lack of) effect
      of NO synthase inhibitors on bradykinin-induced coronary vasodilatation.

PMID- 9535153
TI  - Influence of angiotensin converting enzyme inhibition and angiotensin II type 1
      receptor antagonism on renal sodium and water handling and albuminuria during
      infusion of atrial natriuretic factor into healthy volunteers.
AB  - BACKGROUND: Atrial natriuretic factor increases urinary sodium and water
      excretion. It also causes an increase in albuminuria. Angiotensin converting
      enzyme inhibition attenuates the effects of atrial natriuretic factor on renal
      sodium and water handling; however, it is not known whether this effect is
      mediated by the accompanied decrease in blood pressure or by suppression of the
      renin-angiotensin system. OBJECTIVE: To test the hypothesis that atrial
      natriuretic factor mediates natriuresis and diuresis by inhibiting angiotensin
      II, by studying the effects of the angiotensin converting enzyme inhibitor
      enalapril and the angiotensin II type 1 receptor antagonist losartan. In
      addition, the effects of these drugs on atrial natriuretic factor-induced
      albuminuria were examined. DESIGN AND METHODS: We investigated the effects of
      enalapril and losartan on atrial natriuretic factor-induced changes in urinary
      excretion of sodium, water and albumin from eight healthy volunteers.
      Measurements of systemic and renal haemodynamics in these subjects were performed
      before and during a 2 h infusion of atrial natriuretic factor [0.01 microg/kg per
      min (low dose) for the first 60 min and 0.02 microg/kg per min (high dose) for
      the second 60 min]. Measurements were performed after 5 days of pretreatment with
      placebo, 50 mg losartan or 20 mg enalapril daily. RESULTS: Mean arterial
      pressures during the clearance study were 84.6 +/- 1.7 mmHg after placebo, 84.0
      +/- 2.2 mmHg after losartan treatment and 80.0 +/- 2.5 mmHg after enalapril
      treatment (P < 0.05). Plasma renin activity was significantly increased both by
      losartan and by enalapril treatments. Neither enalapril nor losartan treatment
      attenuated atrial natriuretic factor-induced changes in renal haemodynamics.
      After placebo pretreatment, fractional urinary excretion of sodium increased
      significantly during infusion of atrial natriuretic factor. Losartan treatment
      did not influence the increase in urinary excretion of sodium during infusion of
      atrial natriuretic factor, whereas enalapril treatment significantly attenuated
      this increase (P < 0.01). Atrial natriuretic factor significantly increased
      albuminuria. Neither losartan nor enalapril treatment reduced atrial natriuretic
      factor-induced albuminuria. CONCLUSIONS: Enalapril treatment lowered blood
      pressure and attenuated the atrial natriuretic factor-induced increase in urinary
      excretion of sodium. In contrast, the angiotensin II type 1 receptor antagonist
      losartan, at a dosage that did not lower blood pressure, did not attenuate the
      increase in urinary excretion of sodium. These data indicate that atrial
      natriuretic factor increases natriuresis and diuresis independently of
      angiotensin II. The increase in albuminuria during infusion of atrial natriuretic
      factor was not influenced by enalapril and losartan treatments.

PMID- 9535154
TI  - Course of blood pressure within the first 12 h of hypertensive urgencies.
AB  - OBJECTIVE: To evaluate the course of blood pressure within 12 h of a hypertensive
      urgency with or without oral antihypertensive treatment prior to discharge of
      patients from hospital. DESIGN: A prospective, double-blinded, placebo-controlled
      and randomized clinical trial. SETTING: Department of Emergency Medicine in a
      2000-bed inner city hospital. PATIENTS: Forty patients successfully treated for a
      hypertensive urgency with intravenous administration of urapidil. INTERVENTIONS:
      We administered 60 mg urapidil orally or placebo prior to discharge of patients
      from hospital and evaluated the course of blood pressure within 12 h of the
      urgency by use of an ambulatory blood pressure measurement unit. MAIN OUTCOME
      MEASURES: Mean systolic and diastolic blood pressures within the first 12 h of a
      hypertensive urgency and the number of hypertensive and hypotensive episodes.
      RESULTS: Mean systolic and diastolic blood pressures were significantly lower in
      members of the urapidil group than they were in members of the placebo group (132
      +/- 14 versus 147 +/- 18 mmHg, P = 0.003; 79 +/- 12 versus 87 +/- 14 mmHg, P =
      0.047, respectively). The number of hypotensive episodes was similar for these
      two groups (three versus one, P = 0.32), whereas the number of hypertensive
      episodes was significantly lower for the urapidil group (13 versus 34, P =
      0.001). CONCLUSIONS: Oral medication with urapidil prior to discharge results in
      lower overall blood pressure levels and reduces the risk of hypertensive episodes
      recurring within 12 h of a hypertensive urgency. Therefore, we recommend this
      therapeutic approach for patients with hypertensive urgencies, who are treated
      with an intravenous antihypertensive drug.

PMID- 9535155
TI  - Measurement of left ventricular mass in man.

PMID- 9535156
TI  - Analysis of Wolbachia protein synthesis in Drosophila in vivo.
AB  - Intracellular Wolbachia infections are extremely common in arthropods and exert
      profound control over the reproductive biology of the host. However, very little
      is known about the underlying molecular mechanisms which mediate these
      interactions with the host. We examined protein synthesis by Wolbachia in a
      Drosophila host in vivo by selective metabolic labelling of prokaryotic proteins
      and subsequent analysis by 1D and 2D gel electrophoresis. Using this method we
      could identify the major proteins synthesized by Wolbachia in ovaries and testes
      of flies. Of these proteins the most abundant was of low molecular weight and
      showed size variation between Wolbachia strains which correlated with the
      reproductive phenotype they generated in flies. Using the gel systems we employed
      it was not possible to identify any proteins of Wolbachia origin in the mature
      sperm cells of infected flies.

PMID- 9535157
TI  - A sex-linked Ace gene, not linked to insensitive acetylcholinesterase-mediated
      insecticide resistance in Culex pipiens.
AB  - An acetylcholinesterase (AChE) gene, Ace.x, showing 93% identity of deduced amino
      acid sequence to Anopheles stephensi Ace has been cloned from a Culex pipiens
      strain homozygous for insensitive AChE (iAChE) mediated insecticide resistance.
      DNA sequence of genomic DNA clones identified exons 2-5. RFLP of six clones
      indicated four possible alleles. Linkage analysis located Ace.x to chromosome I,
      less than 0.8 centimorgans from the sex locus, whereas the locus conferring
      resistance was 2.0 centimorgans from plum-eye on chromosome II. Ace.1 coding for
      AChE1, which is associated with resistance, is therefore autosomal. We propose
      that Ace.x is the recently postulated Ace.2 coding for the biochemically distinct
      AChE2, which is not associated with resistance.

PMID- 9535158
TI  - Low substitution rates in mitochondrial DNA in Mediterranean carabid beetles.
AB  - The estimation of DNA substitution rates requires calibration with the geological
      events which caused the separation of populations. We used the disintegration of
      the landbridges between Morocco and Gibraltar as well as the Balearics and Spain
      at the end of the Messinian event (5.3 myr) in order to calibrate the DNA
      sequence data of the NADH-dehydrogenase subunit 1 (ND1) in West Mediterranean
      Carabus species. The rates of molecular evolution we found are much lower than
      those reported in the literature and also vary from species to species.
      Therefore, in insects the calculation of divergence periods using a constant 2%
      substitution rate per myr is questionable.

PMID- 9535159
TI  - Evolutionary relationships among the Braconidae (Hymenoptera: Ichneumonoidea)
      inferred from partial 16S rDNA gene sequences.
AB  - Phylogenetic relationships among the Braconidae were examined using homologous
      16S rDNA gene sequence data. Analyses recovered the few well-supported
      relationships evident in this family from morphological analyses, viz the
      monophyly of the microgastroid complex of subfamilies, the monophyly of the
      cyclostome complex of subfamilies (= braconoids), a sister-group relationship
      between the Alysiinae and Opiinae, and a close relationship between the
      Helconinae and Blacinae. With respect to the braconoid complex of subfamilies, a
      sister-group relationship was recovered between Aphidiinae and Mesostoinae, and a
      clade composed of Gnamptodontinae + Histeromerinae + Rhyssalinae + Aphidiinae +
      Mesostoinae was also recovered. The Doryctinae and Rogadinae sensu lato (s.l.)
      were generally not resolved as monophyletic. With respect to the helconoid
      complex of subfamilies, a sister-group relationship was recovered between
      Sigalphinae and Agathidinae, whereas Neoneurinae fell out among other helconoid
      subfamilies. Other relationships among the helconoid subfamilies were unclear
      from these analyses. With respect to the microgastroid complex of subfamilies,
      our data conform to morphological estimates, recovering ((Microgastrinae +
      Miracinae) + Cardiochilinae) + Cheloninae. The topology of our trees suggests
      that the cyclostome subfamilies are a natural derived group, inferring that
      endoparasitism (not ectoparasitism) is the ancestral state for the Braconidae,
      unless all of the ectoparasitic ancestors of the helconoid + microgastroid
      subfamilies are now extinct.

PMID- 9535160
TI  - Isolation of seven unique biogenic amine receptor clones from the honey bee by
      library scanning.
AB  - The biogenic amine receptor genes constitute an ancient and highly divergent
      family within the larger superfamily of G-protein-coupled receptors. These
      receptors play a central role in modulating nerve cell activity and thus
      behaviour. Because the honey bee offers numerous advantages for behavioural
      studies we endeavoured to isolate as many members of this gene family as possible
      from the bee. We compared numerous approaches to gene isolation and found that
      PCR amplification from small subfractions of cDNA or genomic DNA libraries
      enabled us to isolate clones that are otherwise undetectable. In total we
      isolated seven biogenic amine receptor clones and identified five additional
      related sequences by low-stringency Southern hybridization. Two clones, AmBAR4
      and AmBAR6, are 84% and 72% identical to the Drosophila 5-HT2 and D1b receptors,
      respectively, and probably represent orthologous genes. Phylogenetic analysis
      indicates that AmBAR5 clusters loosely with a variety of tyramine and octopamine
      receptors with which it shares <66% identity. The other four clones, AmBAR1,
      AmBAR2, AmBAR3 and AmBAR7, are weakly to moderately related (28-45% identical) to
      Drosophila dopaminergic or mammalian adrenergic receptors and probably represent
      receptors of these classes whose orthologues have not previously been isolated
      from any insect. The honey bee clones expand the size of the known insect
      biogenic amine receptor gene family to sixteen members. Therefore the size of the
      biogenic amine receptor gene family of insects approaches that of vertebrates.
      This is true despite the reduced behavioural and genetic complexity of the
      insects relative to vertebrate animals.

PMID- 9535161
TI  - Inferences about orthopteroid phylogeny and molecular evolution from small
      subunit nuclear ribosomal DNA sequences.
AB  - We determined DNA sequences of SSU rRNA genes in twenty-nine polyneopteran insect
      species and aligned these with homologues from eight other insects. In a
      phylogenetic analysis we recovered the classic divisions of Palaeoptera and
      Neoptera, with the latter divided into monophyletic Paraneoptera and
      Polyneoptera. The polyneopterans divided into three lineages: one includes the
      Grylloblattodea, Dermaptera and Plecoptera, the second contains the Blattodea,
      and the third (Orthopteroidea sensu Hennig) contains the Embiidina, Phasmida, and
      Orthoptera, in that order. The monophyly of the Orthoptera is supported by the
      analyses, as is the separation between taxa from its suborders Caelifera and
      Ensifera. The Caelifera are not always supported as a monophyletic group; the
      basal Tridactyloidea are separated from the rest of the Caelifera in some
      analyses. Inside of Tridactyloidea, the Acridoidea, Pamphagoidea, Pneumoroidea
      and Trigonopterygoidea are always recovered as a monophyletic group. We also
      examined the basal orthopteran relationships, with the specific aim of assessing
      the antiquity of the Ensifera. Character state reconstructions indicated that the
      ancestral ensiferan sequence is very similar to the ancestral orthopteran
      sequence. However, likelihood ratio tests rejected the null hypothesis of a
      molecular clock and we conclude that a change in substitution rate has occurred
      within the Orthoptera and several of the other polyneopteran orders. Similar
      observations have been made in holometabolous insects, suggesting that variation
      in substitution rate is a general feature of insect nuclear rRNA evolution.

PMID- 9535162
TI  - Molecular characterization of pyrethroid knockdown resistance (kdr) in the major
      malaria vector Anopheles gambiae s.s.
AB  - Pyrethroid-impregnated bednets are playing an increasing role for combating
      malaria, especially in stable malaria areas. More than 90% of the current annual
      malaria incidence (c. 500 million clinical cases with up to 2 million deaths) is
      in Africa where the major vector is Anopheles gambiae s.s. As pyrethroid
      resistance has been reported in this mosquito, reliable and simple techniques are
      urgently needed to characterize and monitor this resistance in the field. In
      insects, an important mechanism of pyrethroid resistance is due to a modification
      of the voltage-gated sodium channel protein recently shown to be associated with
      mutations of the para-type sodium channel gene. We demonstrate here that one of
      these mutations is present in certain strains of pyrethroid resistant A. gambiae
      s.s. and describe a PCR-based diagnostic test allowing its detection in the
      genome of single mosquitoes. Using this test, we found this mutation in six out
      of seven field samples from West Africa, its frequency being closely correlated
      with survival to pyrethroid exposure. This diagnostic test should bring major
      improvement for field monitoring of pyrethroid resistance, within the framework
      of malaria control programmes.

PMID- 9535163
TI  - Molecular cloning and nucleotide sequence of a cytochrome P450 cDNA from a
      pyrethroid-resistant mosquito, Culex quinquefasciatus say.
AB  - A novel cDNA clone encoding a cytochrome P450 was screened from a gut cDNA
      library of permethrin-resistant Culex quinquefasciatus larvae. Nucleotide
      sequence of the clone designated CYP6E1 was determined. This is the first full
      length sequence of a mosquito P450 cDNA. Comparison of the deduced amino acid
      sequence of CYP6E1 to those of other known cytochrome P450s indicates that this
      clone belongs to CYP6 family. In addition, a phylogenetic analysis of CYP6E1
      primary structure showed that it is related to CYP6A and CYP6C subfamilies.
      Polymerase chain reaction (PCR) using primers designed on the basis of the
      nucleotide sequence of the cDNA showed that mRNA encoding CYP6E1 is present in
      permethrin-susceptible larvae as well as -resistant larvae, suggesting the
      ubiquitous distribution of CYP6E1.

PMID- 9535164
TI  - Novel mutations in the para-homologous sodium channel gene associated with
      phenotypic expression of nerve insensitivity resistance to pyrethroids in
      Heliothine lepidoptera.
AB  - Coding sequences from the intracellular segment linking repeat domains III and IV
      of the para-homologous sodium channel gene were amplified and cloned from two
      species of Heliothine larvae using RT-PCR techniques. Sequence comparisons
      between standard laboratory susceptible and nerve insensitive strains of the
      tobacco budworm (Heliothis virescens) and the cotton bollworm (Helicoverpa
      armigera) identified two mutations. These were an aspartic acid (GAC) to valine
      (GTC) and a glutamic acid (GAA) to glycine (GGA) mutation. PCR and sequencing was
      undertaken only on individuals that were demonstrated to be phenotypically nerve
      insensitive or susceptible to pyrethroids using a neurophysiological technique.
      The finding of identical mutations across two species suggests that they may be
      implicated in resistance.

PMID- 9535165
TI  - Lack of nucleotide variability in a beetle pest with extreme inbreeding.
AB  - The coffee berry borer beetle Hypothenemus hampei (Ferrari) (Curculionidae:
      Scolytinae) is the major insect pest of coffee and has spread to most of the
      coffee-growing countries of the world. This beetle also displays an unusual life
      cycle, with regular sibling mating. This regular inbreeding and the population
      bottlenecks occurring on colonization of new regions should lead to low levels of
      genetic diversity. We were therefore interested in determining the level of
      nucleotide variation in nuclear and mitochondrial genomes of this beetle
      worldwide. Here we show that two nuclear loci (Resistance to dieldrin and ITS2)
      are completely invariant, whereas some variability is maintained at a
      mitochondrial locus (COI), probably corresponding to a higher mutation rate in
      the mitochondrial genome. Phylogenetic analysis of the mitochondrial data shows
      only two clades of beetle haplotypes outside of Kenya, the proposed origin of the
      species. These data confirm that inbreeding greatly reduces nucleotide variation
      and suggest the recent global spread of only two inbreeding lines of this bark
      beetle.

PMID- 9535166
TI  - Drug targeting via retrometabolic approaches.
AB  - Retrometabolic approaches incorporate targeting and metabolic considerations into
      the drug design process and represent a novel, systematic methodology for the
      design of safe, localized compounds. Two major design concepts aimed to increase
      the therapeutic index of drugs were developed. Chemical delivery systems allow
      targeting of active biological molecules to specific target sites or organs,
      based on predictable enzymatic activation. Soft drug approaches are used to
      design new drugs by building in the molecule, in addition to the activity, the
      most desired way in which the molecule is to be deactivated and detoxified
      subsequent to exerting its biological effects. Many examples are provided;
      related computer programs are also briefly discussed.

PMID- 9535167
TI  - Thymidylate synthase: structure, inhibition, and strained conformations during
      catalysis.
AB  - Thymidylate synthase (TS) is a long-standing target for chemotherapeutic agents
      because of its central role in DNA synthesis, and it is also of interest because
      of its rich mechanistic features. The reaction catalyzed by TS is the methylation
      of dUMP, with the transferred methyl group provided by the cofactor
      methylenetetrahydrofolate (CH2THF). Recently, several crystal structure
      determinations and mechanistic studies have led to a deeper understanding of the
      TS reaction mechanism, and address the role of conformational change in TS
      catalysis and inhibition. Included among these structures are complexes of TS
      bound to substrate dUMP; cofactor CH2THF; the nucleotide analogs 5-fluoro-dUMP, 5
      nitro-dUMP and dGMP; and the promising antifolates BW1843, ZD1694, and AG337.
      From these studies, a picture of TS emerges where ligand-induced conformational
      changes play key roles in catalysis by straining the thiol adduct that occurs
      during the reaction; by protecting the highly reactive reaction intermediates;
      and by providing a means to stabilize a high-energy conformer of the cofactor
      after initial binding of a low-energy conformer. The best inhibitors of TS also
      induce and stabilize a conformational change in TS. One inhibitor, BW1843,
      distorts the active site on binding, and intercalates into a hydrophobic patch
      between two mobile subdomains in the protein. Also discussed are recent
      developments in the cell biology and regulation of eukaryotic TS and the use of
      structure-based drug design in the development of the antifolates currently in
      clinical trial for the treatment of cancer.

PMID- 9535168
TI  - Arisugacins, selective acetylcholinesterase inhibitors of microbial origin.
AB  - Synthetic inhibitors of acetylcholinesterase (AChE) recently have attracted
      particular attention for treatment of Alzheimer's disease. By systematic
      screening of microbial metabolites, we were able to discover the new AChE
      inhibitors, named arisugacins A and B, from the culture broth of Penicillium sp.
      FO-4259. The structures of arisugacins are members of the meroterpenoid
      compounds. Arisugacin A is a potent and highly selective inhibitor of AChE but
      does not inhibit butyrylcholinesterase in vitro. Arisugacin A is a good candidate
      as an excellent potential drug for treatment of Alzheimer's disease. Also
      reviewed is the current status of development of antidementia drugs.

PMID- 9535170
TI  - The mitomycin bioreductive antitumor agents: cross-linking and alkylation of DNA
      as the molecular basis of their activity.
AB  - This review focuses on the chemical and enzymatic aspects of the reductive
      activation of mitomycin C, its disulfide analogs KW-2149 and BMS-181174, and, in
      less detail, FR66979 and FR900482, newly discovered antitumor antibiotics related
      to mitomycins. Furthermore, structural aspects of DNA damage induced by these
      drugs in vitro and in vivo are described, including the chemical and
      conformational characteristics of DNA interstrand and intrastrand cross-links and
      monofunctional alkylation products, with emphasis on DNA adducts of mitomycin C.
      The DNA sequence specificity of the damage and its mechanism is reviewed. The
      relationship between the chemical and structural properties of the DNA damage on
      the one hand, and the antitumor and other biological activities of the mitomycins
      on the other, is discussed.

PMID- 9535169
TI  - Small molecule inhibitors of the platelet-derived growth factor receptor, the
      fibroblast growth factor receptor, and Src family tyrosine kinases.
AB  - The inhibition of tyrosine kinases involved in growth factor signal transduction
      pathways represents an attractive strategy for controlling aberrant cellular
      growth. Over the last 4-5 years, there have been numerous reports on the
      discovery of small molecule inhibitors for potential therapeutic applications to
      a number of proliferative diseases, principally cancer and restenosis, where the
      over-expression of certain tyrosine kinases has been demonstrated. These include,
      amongst others, the platelet-derived growth factor receptor, the fibroblast
      growth factor receptor, and the nonreceptor c-Src tyrosine kinase. This review
      compiles published reports and patent filings from 1995 to mid-1997 that include
      data directly related to inhibition of the platelet-derived growth factor
      receptor, fibroblast growth factor receptor, and Src family tyrosine kinases.
      Potential clinical applications for selected classes of tyrosine kinase
      inhibitors reviewed herein will likely depend on the demonstration of meaningful
      activity in a variety of therapeutic targets in animal models.

PMID- 9535171
TI  - Novel nicotinamide adenine dinucleotide analogues as potential anticancer agents:
      quest for specific inhibition of inosine monophosphate dehydrogenase.
AB  - Synthetic nicotinamide adenine dinucleotide (NAD) analogues containing 5-beta-D
      ribofuranosylnicotinamide (C-NAD), 6-beta-D-ribofuranosylpicolinamide (C-PAD), 3
      beta-D-ribofuranosylbenzamide (BAD), and 2-beta-D-ribofuranosylthiazole-4
      carboxamide (TAD) in place of the nicotinamide riboside moiety are described and
      evaluated as potential inhibitors of inosine monophosphate dehydrogenase (IMPDH).
      TAD and BAD showed potent inhibitory activity against the enzyme in the form of
      pyrophosphates, as well as metabolically stable methylene- and
      difluoromethylenebis(phosphonate)s. Fluorination at the C2' (ribo and arabino
      configuration) and C3' (ribo) of the adenosine moiety of TAD afforded analogues
      highly potent against IMPDH, but weakly active against alcohol dehydrogenase.
      With the exception of the methylenebis(phosphonate) analogue of TAD compounds
      containing a methylene bridge were poor inhibitors of growth of K562 cells. On
      the other hand, NAD analogues containing difluoromethylene linkage were highly
      effective in inhibition of K562 cell growth, as well as potent inducers of K562
      cell differentiation. Such compounds, therefore, may be of potential therapeutic
      interest.

PMID- 9535172
TI  - Molecular basis for thymidine modulation of the efficacy and toxicity of
      alkylating agents.
AB  - The antitumor activity of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) in mice
      previously was shown to be markedly enhanced by co-administration of thymidine.
      We have examined the cellular mechanisms underlying the augmentation effect of
      thymidine. It was found that thymidine did not increase the cytotoxicity of BCNU
      for B16/F10 melanoma or L1210 leukemia cells in vitro. Instead, thymidine
      appeared to augment the activity of tumor-specific cytotoxic T-cells in tumor
      bearing mice, which specifically rejected a secondary challenge with the B16/F10
      tumor. Thus, development of an antitumor immune response is facilitated by
      thymidine in BCNU-induced immunosuppressed mice. These preclinical studies
      suggested that combination therapy with alkylating agents and thymidine may be a
      more efficacious and less toxic anticancer therapy. The potential efficacy of the
      sequential administration of dacarbazine (DTIC), BCNU, and thymidine in patients
      with advanced malignant melanoma was investigated. As predicted from animal
      studies, sequential administration of DTIC, BCNU, and thymidine is a relatively
      nontoxic therapy for metastatic melanoma. This treatment induced durable
      responses in up to 35% of patients, and hence is superior to many commonly used
      toxic combination chemotherapies. The mechanism of action, although not well
      characterized, is thought to be mediated through protection of the cellular
      immune process, as well as organ function, from alkylating agent toxicity through
      modulation of DNA repair enzymes such as O(6)-alkylguanine-DNA alkyltransferase
      in normal tissue. Thus, thymidine is a biomodulator, which not only protects
      patients from hematologic, pulmonary, and hepatic toxicities associated with DTIC
      and BCNU chemotherapy, but also potentiates therapeutic efficacy.

PMID- 9535174
TI  - Antimalarial activity of synthetic analogues of distamycin.
AB  - Malaria, one of the most serious diseases transmitted by arthropods, is largely
      present in tropical and even temperate zones in endemic or epidemic form. More
      than 40% of the world's population lives in areas at risk for exposure, and the
      World Health Organization reports that approximately 300 million people are
      affected by the infection (mostly caused by the species Plasmodium falciparum),
      with 1-2 million deaths per year. These data, and the fact that malaria is
      becoming increasingly refractory to treatment through resistance of the parasite
      to antimalarial agents currently in use, e.g., chloroquine, emphasize the need to
      develop new drugs. The well-known antiparasitic activity of oligopyrrolamidine
      natural products, such as distamycin and netropsin, suggested the antimalarial
      evaluation of related compounds obtained by new chemical modifications. Besides
      possessing antiviral and antitumoural properties, distamycin exhibits interesting
      in vitro activity against P. falciparum. Unfortunately, the high toxicity
      associated with this product precludes its development as a drug. However, some
      synthetic analogues of distamycin proved to be highly active against chloroquine
      sensitive and -resistant strains of P. falciparum, besides showing low toxicity
      in vitro.

PMID- 9535173
TI  - New developments in antitumor anthracyclines.
AB  - Doxorubicin is a major anticancer agent introduced to extended clinical use in
      the early 1970s. The fulfillment of a wide program of analogue synthesis led to
      the development of the better tolerated epirubicin and of a highly potent
      antileukemic drug, idarubicin. In recent years, on the basis of the available
      information on the molecular requirements for action, a new synthetic program,
      coupled with target-oriented pharmacological experiments, was carried out.
      Various interesting derivatives, namely, the 8- and 10-fluoro compounds and the
      disaccharides, were obtained. The latter compounds exhibited a strong dependence
      of biological activity on the orientation (axial vs. equatorial) of the second
      sugar moiety, daunosamine. A member of this group, namely, 7-O-(4'-O-alpha-L
      daunosaminyl-2'-deoxy-alpha-L-fucosyl)-4-demetho xy-adriamycinone, is presently
      undergoing clinical trials as a third generation antitumor anthracycline.

PMID- 9535175
TI  - Therapeutic approaches to human immunodeficiency virus: structural studies on G
      protein-coupled receptors.
AB  - Infection by human immunodeficiency virus (HIV) requires the presence of a
      chemokine receptor on the susceptible cell. The expression of two different
      chemokine receptors on macrophages and lymphocytes explains the selectivity of
      different HIV isolates. The rationale behind the choice of the chemokine receptor
      (CCR5) expressed on macrophages as a therapeutic target is based on the
      epidemiological studies of the impact on HIV infectivity of a human mutation that
      prevents expression of this receptor. CCR5 is a member of the G-protein-coupled
      receptor family, which has yet to be characterized structurally at atomic
      resolution. Efforts to model the three-dimensional structure of such receptors
      and to characterize them experimentally are underway in many laboratories. As an
      example, structural studies determining the bound conformation of the C-terminal
      peptide of the alpha-subunit of transducin, the relevant G-protein of vision,
      with rhodopsin are presented.

PMID- 9535176
TI  - Acute promyelocytic leukemia: cellular and molecular basis of differentiation and
      apoptosis.
AB  - Acute promyelocytic leukemia (APL) accounts for about 10% of all acute myeloid
      leukemias and is characterized by the chromosomal translocation t(15;17), which
      fuses the retinoic acid receptor (RAR) alpha gene to the promyelocytic leukemia
      (PML) gene. The PML-RAR alpha fusion gene plays an important role in
      leukemogenesis through antagonizing retinoic acid signalling and the regulatory
      pathways mediated by PML. APL is the first example of a human cancer that can be
      effectively treated with the differentiation inducer all-trans retinoic acid
      (ATRA). The therapeutic effect of ATRA in APL has been associated with the direct
      modulation of PML-RAR alpha, the restoration of the differentiation pathways
      regulated by wild-type RAR/retinoid X receptor heterodimer and PML. More
      recently, a second drug, arsenic trioxide (As2O3), has been discovered in China
      that also has a strong therapeutic effect against APL. As2O3 can induce clinical
      remission in de novo or relapsed APL patients and has no cross-resistance with
      ATRA. It has dual effects on APL cells: preferential apoptosis at high
      concentration (0.5-2 microM) and partial differentiation at low concentration
      (0.1-0.5 microM). Modulation and degradation of PML-RAR alpha proteins can be
      induced by As2O3 and probably contribute to these two effects. These studies lead
      to a model in which PML-RAR alpha could be the target of both ATRA
      differentiation therapy and As2O3 apoptosis therapy.

PMID- 9535178
TI  - Modulation of plasminogen activator inhibitor type-1 biosynthesis in vitro and in
      vivo with oligo(nucleoside phosphorothioate)s and related constructs.
AB  - Oligonucleotides with a nucleotide sequence complementary to various regions of
      human plasminogen activator inhibitor type-1 (PAI-1) mRNA have been studied as
      antisense inhibitors of expression of PAI-1 protein in cultured cells [human
      umbilical vein endothelial cells (HUVEC), human aortic smooth muscle cells, human
      hybrid endothelial cells]. Hexadeca(deoxyribonucleoside phosphorothioate) 13
      complementary to a fragment of a signal peptide PAI-1 mRNA was found to be most
      active, giving ca. 70% inhibition of PAI-1 release in a time- and dose-dependent
      way. The stereo-regular All-S(P) and All-R(P) diastereomers of 13 were studied
      and found to inhibit PAI-1 synthesis in HUVEC in a stereo-dependent manner, with
      the All-S(P) diastereomer considerably more active than the stereo-random
      construct and All-R(P) isomer. The observed stereo-dependent activity of
      oligonucleotide phosphorothioate constructs is presumably governed by their
      resistance to nucleases. The corresponding phosphodiester analogue of 13 was not
      active unless covalently bound at its 5'-end to a lipophilic alcohol residue
      (menthol, heptadecanol). The observed antisense activity of phosphodiester
      oligonucleotide bioconjugates in cultured human hybrid endothelial cells was
      paralleled by their increased stability in human plasma with respect to
      unconjugated oligonucleotide. The oligo(deoxyribonucleoside phosphorothioate)
      complementary to the same signal peptide region of rat PAI-1 mRNA was found to
      reduce the PAI-1 level in blood plasma of rats after intravenous administration
      into the tail vein. The effect was both time- and dose-dependent. The same
      oligonucleotide was found to protect against arterial thrombus formation in the
      rat (lower incidence of venous thrombosis, lower thrombus weight, and increased
      occlusion time in experimentally induced thrombosis). An anti-PAI-1 inhibitory
      activity has been independently reported for a 20-mer oligo(2'-O-methyl
      ribonucleoside phosphorothioate) complementary to a 3'-untranslated region of
      human PAI-1 mRNA in cultured HUVEC and human aortic smooth muscle cells.

PMID- 9535177
TI  - Perspectives in antisense therapeutics.
AB  - Modulation of gene expression using oligonucleotides (oligos) is currently an
      area of intense activity, both from therapeutic, as well as research
      perspectives. To develop oligos as therapeutic agents, in addition to
      demonstrable biological activity, in vivo metabolic stability, tissue disposition
      and pharmacokinetics are important considerations. Oligodeoxynucleoside
      phosphorothioates are the first-generation antisense analogs that have been
      studied extensively, and are in clinical trials against a number of disease
      indications. In an effort to improve the antisense properties of these compounds,
      mixed-backbone oligos incorporating different chemical modifications have been
      synthesized and evaluated for antisense activity. The present review will provide
      an overview of the pharmacokinetics and toxicology following intravenous,
      intraperitoneal, subcutaneous and oral administration of mixed-backbone oligos as
      second-generation antisense therapeutics.

PMID- 9535179
TI  - Role of apoptotic response in cellular resistance to cytotoxic agents.
AB  - The development of drug resistance is a major obstacle to effectiveness of
      chemotherapeutic treatment of human tumors with cytotoxic agents. Drug resistance
      is described as a multifactorial phenomenon, involving the expression of defense
      factors and/or detoxification mechanisms, alterations in drug-target
      interactions, and cellular response to specific cytotoxic lesions (in particular,
      DNA damage). Although the proposed mechanisms may contribute to the development
      of a variable degree of cellular resistance, it is possible that the cell
      response (i.e., DNA repair or apoptosis) following DNA damage plays a critical
      role in determining cellular chemosensitivity. The preclinical observations that
      tumor response to effective drug treatments is associated with induction of
      apoptosis support the possibility that a decreased susceptibility to apoptosis
      (apoptosis resistance) is relevant to clinical resistance. A number of molecular
      alterations associated with transformation and/or tumor progression may also be
      implicated in regulation of cell death pathways and in the development of drug
      resistance. There is evidence that the wild-type p53 is involved in cellular
      response to DNA damage, including cell cycle regulation, DNA repair, and
      activation of the pathway leading to apoptosis. Loss of wild-type p53 function
      could cause resistance to DNA-damaging agents, as a consequence of abrogation of
      p53-dependent apoptosis. The identification of new agents able to trigger p53
      independent apoptosis and the search for biochemical modulators downstream of p53
      may be of clinical relevance because many tumors are deficient in p53 function
      due to mutation or deletion. An overview of the resistance mechanisms is
      presented, with particular reference to the role of p53 mutations in clinical
      resistance and of apoptosis-related genes in cellular chemosensitivity.

PMID- 9535180
TI  - Beta-N-acetylhexosaminidase: a target for the design of antifungal agents.
AB  - This review provides biochemical, analytical, and biological background
      information relating to beta-N-acetylhexosaminidase (HexNAc'ase; EC 3.2.1.52) as
      an emerging target for the design of low-molecular-weight antifungals. The
      article includes the following: (1) a biochemical description of HexNAc'ase
      (reaction catalyzed, nomenclature, and mechanism of action) that sets it apart
      from other, similar enzymes; (2) an overview and a critical evaluation of methods
      to assay the enzyme, including in crude extracts (photo- and fluorometric
      procedures with model substrates; HPLC/pulsed amperometric detection of N
      acetylglucosamine and chito-oligomers; end-point vs. rate measurements); (3) a
      summary of some general characteristics of HexNAc'ases from fungi and organisms
      of other types (Km values, substrate preference, and glycoconjugation); (4) an
      hypothesis of a specific target function of wall-associated HexNAc'ase (a
      component of the assembly of surface-located enzymes effecting a continuous
      turnover and remodelling of the wall fabric through its combined hydrolytic and
      transglycosylating activities, and a mediator enzyme acting in concert with
      chitinase and chitin synthase to provide for the controlled lysis and synthesis
      of chitin during growth); (5) a tabulation of the structural formulae of reaction
      based HexNAc'ase inhibitors with Ki values < or = 100 microM (some of them
      representing transition state mimics that could serve as leads for the
      development of new antifungals); and (6) an outline of approaches towards the
      establishment of a three-dimensional model of HexNAc'ase suitable for a truly
      rational design of antimycotics as well as agricultural fungicides.

PMID- 9535181
TI  - Active efflux by multidrug transporters as one of the strategies to evade
      chemotherapy and novel practical implications of yeast pleiotropic drug
      resistance.
AB  - Mankind is faced by the increasing emergence of resistant pathogens, including
      cancer cells. An overview of the different strategies adopted by a variety of
      cells to evade chemotherapy is presented, with a focus on the mechanisms of
      multidrug transport. In particular, we analyze the yeast network for pleiotropic
      drug resistance and assess the potentiality of this system for further
      understanding of the mechanism of broad specificity and for development of novel
      practical applications.

PMID- 9535182
TI  - Determination of the main tropane alkaloids from transformed Hyoscyamus muticus
      plants by capillary zone electrophoresis.
AB  - A capillary zone electrophoretic method (CZE) was developed using an uncoated
      fused silica capillary for the separation and determination of the main tropane
      alkaloids. The applicability of the developed method for analysis of plant
      samples was examined by analyzing samples of transgenic Egyptian henbane
      Hyoscyamus muticus (L.) plants. A simple 40 mM phosphate buffer at pH 7.8 using a
      voltage of 20 kV was found the best for this purpose. The main tropane alkaloids,
      atropine and scopolamine as well as nor-(-)-scopolamine, and tropic acid, the
      precursor of tropane alkaloids, could be separated in less than 13 min. The
      linear concentration range for atropine was 5.00-140 microg ml(-1), for
      scopolamine 7.50-210 microg ml(-1) and for tropic acid 2.50-70.0 microg ml(-1).

PMID- 9535183
TI  - Nuclear magnetic resonance spectral analysis and conformational properties of 11
      benzoyl-9,9a,10,11-tetrahydro-4H-indolo[4,3-ab]carbazole.
AB  - The structure of 11-benzoyl-9,9a,10,11-tetrahydro-4H-indolo [4,3-ab] carbazole, a
      candidate molecule to possess significant antitumor or antimicrobial activity,
      was elucidated using a combination of one-dimensional and two-dimensional nuclear
      magnetic resonance (NMR) techniques. Its conformational properties were studied
      using a combination of two-dimensional NOESY spectroscopy and molecular modeling.
      Such information will be of aid to synthetic chemists who aim to develop
      derivatives of this structure. It may also provide information about the
      stereoelectronic requirements that govern their activities.

PMID- 9535184
TI  - The determination of benzalkonium chloride in eye-drops by difference
      spectrophotometry.
AB  - A direct, extraction-free spectrophotometric method was developed for the
      determination of benzalkonium chloride (BAC) in various eye-drops. The procedure
      is based on ion-pair formation between BAC and 2',4',5',7'-tetrabromofluorescein
      (eosin-Y) which decreases the absorbance and induces a bathochromic shift of the
      maximum in the eosin-Y spectrum. The effects of pH, excess of reagent and ionic
      strength on the ion-pair formation have been studied in detail. At pH 4.40 and
      9.62, the working curve is linear in the 1.98 x 10(-6) to 2.40 x 10(-5) M (0.7
      8.5 microg cm[-3]) concentration range; however, the sensitivity drops to about
      one third in the basic solution. At pH 4.40, the analytical signal is stable for
      more than 60 min, while at pH 9.62 the signal changes in time and reaches the
      maximum value 3 min after mixing the reagent and the sample. When the active
      substance is beta-5-isopropyl-2'deoxyuridine and the sample contains typical
      additives, the reproducibility of the analytical signal at pH 4.40 is R.S.D. =
      2.36% (n = 81). In the case of such samples, the linearity of the method is
      somewhat dependent on the composition, but generally acceptable at the 50-150%
      concentration levels. Eye-drops containing tobramycin, an aminoglycoside-type
      antibiotic, as the active substance were analyzed at pH 9.62. This was necessary
      to avoid strong interference from the analyte in acidic solution. In this case
      the linearity of the method is limited to a narrower concentration range;
      however, the recovery is still acceptable at the 100% level.

PMID- 9535185
TI  - Structural elucidation and conformational properties of the immunomodulator
      linomide.
AB  - Linomide is a new synthetic immunomodulator which exerts prominent anti
      autoimmune effects in various experimental models. Recently, it was tested in
      clinical trials to patients suffering from multiple sclerosis and showed to
      inhibit the activity of the disease. Therefore, due to its pharmacological
      importance, we attempted elucidate its structure using one-dimensional and two
      dimensional nuclear magnetic resonance (NMR) techniques and study its
      conformational properties using a combination of two-dimensional NMR spectroscopy
      and molecular modeling. The conformational analysis of linomide was based on the
      measurement of interproton nuclear Overhauser enhancement (NOE) values obtained
      from a two-dimensional NMR spectrum and a number of molecular modeling techniques
      used to calculate the low energy conformers of this compound. This information
      will serve as an aid to synthetic chemists whom their research activity is
      focused on developing linomide analogs with better biological profiles.

PMID- 9535186
TI  - Gas chromatographic method for determination of uracil herbicides in roots of
      Echinacea angustifolia Moench (Asteraceae).
AB  - A GC/NPD method and a rapid screening TLC method were developed for the
      simultaneous determination of uracil herbicide residues (bromacil, lenacil,
      terbacil) in the roots of Echinacea angustifolia Moench (Asteraceae). The uracil
      herbicide residues were extracted into acetone. After evaporation of acetone from
      the acetone-water extract the residue was dissolved in water-methanol (5:1 v/v).
      Cyclohexane was used for removal of the non-polar co-extractives in the sample
      matrix. After separation of the cyclohexane phase the uracil herbicide residues
      were extracted into chloroform. This extract was purified on a Florisil column,
      and residues were eluted with dichloromethane-acetone (9:1, v/v). The cleaned up
      extract was analysed by the GC/NPD method on a capillary column DB-1 using
      atrazine as internal standard. A minimum recovery of 70% was attained for
      contamination levels of 0.02-0.40 mg kg(-1).

PMID- 9535187
TI  - Flow-injection determination of total ammonia and total carbon dioxide in blood
      based on gas-diffusion separation and with a bulk acoustic wave impedance sensor.
AB  - A novel flow-injection (FIA) system, for the rapid and direct determination of
      both total ammonia (T[NH3]) and total carbon dioxide (T[CO2]) in clinical blood
      samples, has been developed. Samples were injected into a carrier stream of H2O,
      then emerged with a reagent stream, where the analyte was converted into a
      gaseous species and diffused across a PTFE gas-permeable membrane into an
      acceptor stream. The trapped NH3/CO2 in the acceptor was determined on line by a
      bulk acoustic wave (BAW) impedance sensor. At a through-put of 20 and 65 h(-1),
      the proposed system exhibited a linear frequency response up to 200 micromol l(
      1) ammonium and 20 mmol l(-1) bicarbonate with a detection limit of 1.0 and 10
      micromol l(-1), respectively. Results obtained for T(NH3) in serum and T(CO2) in
      plasma were in agreement with those obtained by the conventional glutamate
      dehydrogenase (GDH) method and gas-sensing electrode method, respectively. The
      effects of composition of acceptor stream, cell constant of conductivity
      electrode, sample volume, flow rate and potential interferents on the FIA signals
      were also discussed.

PMID- 9535188
TI  - Copper(II) increases bile acid binding to asparagine.
AB  - Interactions of two bile acids (cholic and glycocholic acids) with asparagine
      have been studied by potentiometry in aqueous solutions under conditions similar
      to those observed in biological fluids (37 degrees C and I = 0.15 M NaCl), and in
      the absence and presence of copper(II). To characterize the equilibria for the
      systems copper(II)/bile acid/asparagine, specifically to assess cooperative
      binding between bile acids and asparagine, the acidity constant of asparagine and
      formation constants for copper(II)/bile acid and copper(II)/asparagine were also
      obtained under the same conditions. The results obtained suggest cooperativity in
      the binding of bile acid to asparagine in the presence of copper(II).

PMID- 9535190
TI  - Study of the British Pharmacopeia method on methimazole (thiamazole) content in
      carbimazole tablets.
AB  - The analysis of carbimazole tablets in The British Pharmacopoeia, 1993, includes
      a quantitative thin layer chromatography (TLC) determination of methimazole.
      Repeated analysis of the same samples did not give similar results. The
      repeatability and reproducibility of the method was studied. It was proved that
      the residence time of the methimazole spot on the TLC plate is time dependent.

PMID- 9535189
TI  - Automated 96-well solid phase extraction for the determination of doramectin in
      cattle plasma.
AB  - Automated standard and sample preparation have been coupled with 96-well solid
      phase extraction (SPE) technology to produce a cost effective, high throughput
      system for the analysis of drugs in biological media. The system was originally
      designed using the Packard Multiprobe 104DT robotic sample processor (RSP) to
      improve throughput for the assay of doramectin in cattle plasma, and the assay
      has since been validated (0.5-100 ng ml[-1]) using the Tecan Genesis RSP 150/8.
      The robotic processor conducts all liquid handling procedures involved in sample
      extraction. These comprise preparation of calibration standards in plasma,
      dispensing and diluting of plasma samples and addition of internal standard. In
      addition, the robot primes the 96-well SPE block, applies calibration standards
      and samples, draws the mixtures through the 96-well SPE block, and finally washes
      the block ready for manual elution. The doramectin assay involves high
      performance liquid chromatography (HPLC) with fluorescence detection, and
      requires the sample extracts to be derivatised prior to analysis. The
      derivatisation procedure is performed manually in situ in the polypropylene deep
      96-well block into which the samples have been eluted from the SPE-block. The
      derivatised samples are taken directly from the deep well block and injected into
      the HPLC for analysis. This type of batch processing keeps sample transfer to a
      minimum. Automated sample preparation, in combination with the use of 96-well
      technology, has reduced both cost and effort required in the analysis of
      doramectin in cattle plasma samples, and has resulted in improved sample
      throughput.

PMID- 9535191
TI  - Ion-pair formation of Bi(III)-iodide with some nitrogenous drugs and its
      application to pharmaceutical preparations.
AB  - A systematic spectrophotometric study on the ion-pair formation of Bi(III)-iodide
      with amineptine hydrochloride, piribedil and trimebutine maleate is carried out.
      The optimal experimental conditions pH, concentration of Bi(III) nitrate,
      potassium iodide; and the nature and amount of organic solvent have been studied.
      The ion pairs are soluble in 1,2-dichloroethane and the optimum pH range is 2.0
      2.8. By application of the methods of Sommer and Job involving non-equimolar
      solutions, the conditional stability constant (log K') of the Bi(III) piridedil
      ion pair (1:1) at the optimum pH of 2.4 and an ionic strength (mu) 0.1 M, was
      found to be 5.436. The validity of Beer's law has been tested in the
      concentration range 5-50 microg ml(-1) in the organic layer, the relative
      standard deviation is less than 1%. The method is applied to the determination of
      these drugs in tablets without interference.

PMID- 9535192
TI  - Electroanalytical study of nifedipine using activated glassy carbon electrode.
AB  - The electrochemical properties of nifedipine have been investigated in aqueous
      solution by linear sweep and cyclic voltammetry. The method is based both on the
      reduction and on the oxidation of the drug at a glassy carbon electrode activated
      by applying a new pre-treatment. The voltammograms of nifedipine on pH,
      concentration and scan rate have been carefully examined. Both the
      electroreduction and electrooxidation of nifedipine allow its determination at pH
      1.5 in the concentration range of 2 x 10(-5)-6 x 10(-4) M and 8 x 10(-5)-1 x 10(
      3) M, respectively. The method has been applied to commercial samples (tablets
      and capsules).

PMID- 9535193
TI  - Application of least squares method in matrix form: simultaneous determination of
      ibuprofen and paracetamol in tablets.
AB  - Least squares method in matrix form which is K-matrix representation of Beer's
      law is presented for simultaneous determination of ibuprofen and paracetamol in
      tablets without prior separation from each other. The concentration of each
      component in the mixture was determined spectrophotometrically from absorbances
      of the mixture measured at 225, 226, 228, 232, 230, 234, and 235 nm. Mixtures of
      known composition were used as standards to minimise errors due to presence of
      both compounds in the same solution. Excellent results were obtained by this
      method.

PMID- 9535195
TI  - Active drug substance impurity profiling part II. LC/MS/MS fingerprinting.
AB  - Drug substance impurities are routinely monitored using HPLC. Because HPLC
      retention times can vary, uncertainty can arise as to whether a peak at a new
      retention time is a new impurity. When impurity standards are not available some
      method is needed to characterize the impurities on-line. This work sought to
      assess the ability of LC/MS/MS to generate characteristic impurity
      'fingerprints', comprised of a precursor ion mass plus at least three product ion
      masses. MS/MS fingerprints of a drug substance, DuP 941, and three of its
      impurities were first generated using available standards. Experiments varying
      collision cell parameters showed that collision energy must be specified in order
      to reproducibly generate characteristic MS/MS fingerprints. MS/MS fingerprints
      were also generated on-line for seven impurities in the earliest safety lot of
      DuP 941. Several subsequent lots of DuP 941 were examined to see how well their
      impurity fingerprints matched those from the earlier lot. Fingerprint
      reproducibility was very good for all impurities examined, even down to 0.01 UV
      area percent for some impurities. MS/MS fingerprinting was able to distinguish
      two impurities from one another which were known to be positional isomers. It
      also permitted assignment of tentative structures to the drug impurities.

PMID- 9535194
TI  - Active drug substance impurity profiling part I. LC/UV diode array spectral
      matching.
AB  - Monitoring of drug substance impurities is routinely accomplished using HPLC.
      However, HPLC retention times can vary, resulting in uncertainty as to whether a
      peak at a new retention time is a new impurity. Because standards of the minor
      impurities (less than 0.1% by area) are not usually available, some method is
      needed to characterize each of these peaks without isolating them. This on-line
      characterization might be accomplished using UV diode array spectral matching.
      This work sought to assess the sensitivity and selectivity of UV spectral
      matching for monitoring the impurity profile of drugs, using as an illustration
      DuP 941, an anti-cancer drug under development. An ultraviolet spectral data
      library was generated for a number of the DuP 941 impurities in the earliest
      safety lot. Impurities in several subsequent lots of DuP 941 were then examined
      to see how well their spectral characteristics matched those of the spectra
      contained in the library. We found LC/UV spectral matching to be a powerful
      method to monitor Dup 941 impurities even down to levels well below 0.1% by area.
      Critical factors that were shown to influence the utility of the technique
      include detector sensitivity, lamp intensity, and the presence of other
      impurities with very similar UV spectra.

PMID- 9535196
TI  - Sample pooling to expedite bioanalysis and pharmacokinetic research.
AB  - In the progression from drug discovery to development, not only pharmacokinetic
      (PK) characterization needed for lead compound selection often becomes a rate
      limiting step, but also high volume of routine sample analysis ensued from
      numerous required biodisposition studies for the lead compounds and their back
      ups often place a burdensome hurdle to the throughput of IND and NDA development
      phases. Higher throughput of PK screening via cocktail dosing has been reported
      to accelerate PK screening in the discovery phase. However, concerns on drug-drug
      interactions and other limitations associated with the cocktail M-in-One dosing
      (multiple compounds per dose per animal) has prompted the present investigation
      of sample pooling alongside One-in-One dosing strategy (one compound per dose per
      animal) as an alternative to the cocktail dosing approach. Using traditional HPLC
      for bioanalysis as an example, the present study illustrate the concept and
      usefulness of sample pooling that could facilitate the throughput of PK screening
      and characterization in both discovery and development phases. Six proprietary
      dopamine D4 receptor antagonist preleads representing three different chemical
      classes, used as model compounds (C1-C6), were administered orally to rats. One
      rat received one compound and three rats were used for each compound. Six unknown
      plasma samples from six different rats at each time point were pooled. The pooled
      plasma samples were extracted by a one-step liquid-liquid extraction and
      concentrations of the six preleads were quantitated simultaneously. By sample
      pooling, a substantial amount of PK information was obtained at the same time for
      the six preleads, which requires much less workload than when bioanalysis is
      dealt with one compound at a time. For the first time in one aspect of innovative
      bioanalysis, the present investigation has demonstrated that sample pooling
      following One-in-One dosing can be utilized to enhance the throughput rate in PK
      screening in discovery phase. The sample pooling approach is likely to be useful
      in enhancing the throughput of PK characterization in development phase. With the
      advent of LC-MS and its becoming user-friendly, where separation of drug
      compounds is no longer an issue, the uniqueness of sample pooling may also pose a
      new way of thinking in regard to the old ways of handling bioanalysis for
      traditional PK research.

PMID- 9535197
TI  - Optimised separation of E- and Z- isomers of tamoxifen, and its principal
      metabolites using reversed-phase high performance liquid chromatography.
AB  - A reversed phase isocratic high-performance liquid chromatographic method is
      reported in which a formal structured procedure, the solvent selectivity
      triangle, was applied to predict the mobile phase composition giving baseline
      resolution of the clinically important triphenylethylene antioestrogenic agent
      (Z)-tamoxifen, its principal (Z)-metabolites, and also the clinically relevant
      (E)-geometric isomers of tamoxifen and 4-hydroxytamoxifen. The technique of
      solvent selectivity triangle was used to select the optimal organic modifier
      parameter for use with a Hichrom ODS 1 column, to achieve baseline separation of
      six triphenylethylene solutes. The detection system utilised post-column
      ultraviolet irradiation to convert solutes into their respective photocyclisation
      products, followed by fluorescence detection (lambda[ex] = 254 nm, lambda[em] =
      360 nm), and the low detection limit for tamoxifen in serum of 0.1 microM. The
      optimal mobile phase composition was determined to be methanol-acetonitrile-water
      trichloroacetic acid (50:31:18.9:0.1, v/v, pH 2.9). A single stage liquid-liquid
      extraction method for determination of triphenylethylene drugs in serum was
      developed. Reproducible recoveries for the (Z)-geometric isomers of tamoxifen (84
      +/- 3%) and its principal metabolites including Metabolite Y (94 +/- 3%), N
      desmethyltamoxifen (94 +/- 3%) and 4-hydroxytamoxifen (92 +/- 3%) were achieved,
      though more variable results were obtained for their corresponding (E)-geometric
      isomers (71 +/- 7% and 70 +/- 10%, respectively).

PMID- 9535198
TI  - HPLC assays to simultaneously determine the angiotensin-AT1 antagonist losartan
      as well as its main and active metabolite EXP 3174 in biological material of
      humans and rats.
AB  - Novel rapid and sensitive HPLC assays were developed to simultaneously determine
      losartan and its main active metabolite EXP 3174 in biological material of humans
      and rats following solid-phase or liquid-liquid extraction. The analytes were
      separated on a 3 microm particle-sized ULTREMEX CN column, which was preceded by
      a 5 microm particle-sized guard column, using UV-detection at 245 nm. The assays
      provided high sensitivity with limits of quantification (LoQ) of 5 ng ml(-1) for
      both compounds in human and rat plasma and 10 ng ml(-1) in human and rat urine,
      respectively. In rat blood, bile and various tissues, limits of quantifications
      were achieved that ranged 10-15 ng per ml and per 100 mg tissue, respectively,
      for both analytes.

PMID- 9535199
TI  - Clinical analysis of sampatrilat, a combined renal endopeptidase and angiotensin
      converting enzyme inhibitor I: assay in plasma of human volunteers by atmospheric
      pressure ionisation mass-spectrometry following derivatisation with BF3-methanol.
AB  - Sampatrilat is a dual inhibitor of angiotensin converting enzyme (ACE) and
      neutral endopeptidase (NEP) under development for the treatment of hypertension
      and congestive heart failure. In order to support the early clinical development
      (with oral administration and an expected low bioavailability), a sensitive and
      selective assay was required. A method for plasma was developed and validated
      employing HPLC APCI MS-MS. The plasma samples were extracted on solid-phase
      extraction cartridges, derivatised with BF3-methanol, diluted, extracted again
      and then subjected to HPLC APCI-MS-MS. Derivatisation was necessary because the
      two carboxyl group in the molecule prevented efficient ionisation in the heated
      nebuliser source. The calibration range was from 0.5 to 20 ng ml(-1) and the
      lower limit of quantification was 0.5 ng ml(-1). Imprecision and inaccuracy were
      determined on three separate occasions at three concentrations (0.5, 5 and 20 ng
      ml[-1]) and shown to be lower than 10% in every case.

PMID- 9535200
TI  - Clinical analysis of sampatrilat, a combined renal endopeptidase and angiotensin
      converting enzyme inhibitor II: assay in the plasma and urine of human volunteers
      by dissociation enhanced lanthanide fluorescence immunoassay (DELFIA).
AB  - Sampatrilat is a dual inhibitor of angiotensin converting enzyme (ACE) and
      neutral endopeptidase (NEP) under development for the treatment of hypertension
      and congestive heart failure. In order to support the early clinical development
      (with oral administration and an expected low bioavailability), a sensitive and
      selective assay was required. An HPLC-atmospheric-pressure chemical ionisation
      mass-spectrometric (HPLC-APCI-MS-MS) assay had been already validated (R.F. Venn
      et al., J. Pharm. Biomed. Anal., in press), but due to its low throughput an
      alternative method was sought. As the molecule is peptide-like and not
      metabolised, we believed the immunoassay approach was appropriate. Thus we
      developed an immunoassay for the compound using time-resolved fluorescence as an
      end-point (DELFIA) with lower limits of quantification of 0.2 ng ml(-1) for the
      plasma assay and 5 ng ml(-1) for the assay in urine. This assay is a 96-well
      plate based competitive immunoassay; the end-point is the determination of a (non
      radioactive) europium label by time-resolved fluorimetry. Sampatrilat is labelled
      with chelated europium via isothiocyanate chemistry. The advantage of this assay
      is its extremely high throughput, allowing rapid analysis of many thousands of
      samples. The DELFIA method was successfully cross-validated with the HPLC-APCI-MS
      MS method.

PMID- 9535201
TI  - Application of micellar electrokinetic chromatography for analyzing antiviral
      drugs in pharmaceutical semisolid formulations.
AB  - The application of micellar electrokinetic chromatography (MEKC) to the
      determination of the antiviral drugs brivudin (BV) and aciclovir (AC) in
      pharmaceutical semisolid formulations was studied. A method was developed for
      separating AC and BV both from hydrophilic and from lipophilic semisolid
      formulations and for the rapid determination of BV and AC using MEKC. The
      detection limit, the effective mobility and the relative standard deviation of
      the migration times and of the peak areas were determined.

PMID- 9535202
TI  - Simultaneous determination of chlorzoxazone, indicator of CYP2E1, and its
      metabolite in human serum using a new reversed-phase chromatographic column of 2
      microm porous microspherical silica-gel.

PMID- 9535203
TI  - Catalytic precolumn derivatization of amikacin.

PMID- 9535204
TI  - Ifosfamide and paclitaxel combinations for the treatment of advanced non-small
      cell lung cancer.
AB  - Ifosfamide and paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ)
      are among the most active agents for the treatment of non-small cell lung cancer,
      with single-agent response rates of 20% or greater in previously untreated
      patients with advanced disease. These two agents have been evaluated in several
      phase I and II trials of two-, three-, and four-drug regimens to determine their
      safety and efficacy in this patient population. Ifosfamide and paclitaxel
      doublets were evaluated in two phase I and II trials. Response rates ranged from
      15.4% to 34%, with 1-year survival rates as high as 37%. Toxicity was acceptable,
      with greater degrees of myelosuppression seen with 24-hour infusion times for
      paclitaxel. Three-drug studies of ifosfamide, paclitaxel, and a platinum analogue
      have shown that these three drugs may be combined. Myelosuppression is
      considerable, however, and febrile neutropenia rates are high, even when growth
      factors are used. The addition of etoposide to the three-drug regimens has been
      evaluated only in phase I studies. Myelosuppression increases, and rates of
      febrile neutropenia as high as 26% have been reported. The lack of any suggestion
      of additional efficacy and the substantial toxicity suggest that four-drug
      combinations are not advisable.

PMID- 9535205
TI  - A review of ifosfamide and vinorelbine in advanced non-small cell carcinoma of
      the lung.
AB  - Ifosfamide and vinorelbine have demonstrated single-agent activity against
      advanced non-small cell lung cancer. The dose-limiting toxicity of each agent is
      myelosuppression. Several trials have studied this combination to determine its
      toxicity and efficacy in non-small cell lung cancer. We conducted a dose
      escalation study of vinorelbine in a novel (daily x 3) schedule with ifosfamide
      and granulocyte colony-stimulating factor support to define the dose-limiting
      toxicities and maximum tolerated dose of vinorelbine in this combination. Other
      investigators have studied this combination in the phase II setting. In our phase
      I study involving 42 patients, the recommended phase II dose was vinorelbine 30
      mg/m2 with ifosfamide 1.6 g/m2, each given on 3 consecutive days, followed by
      granulocyte colony-stimulating factor. The overall response rate was 40%, with a
      median survival of 50 weeks. Myelosuppression proved to be dose limiting for this
      regimen, without other major toxicities. Other groups have studied the
      ifosfamide/vinorelbine combination, and studies adding cisplatin to this regimen
      have been conducted as well. Given the tolerable toxicity and encouraging
      response rates and 1-year survival rate seen with this regimen, further
      investigation of the ifosfamide/vinorelbine regimen has continued in a phase II
      Cancer and Leukemia Group B trial. Further study of the potential application of
      the combination as induction therapy for stage III disease is warranted.

PMID- 9535206
TI  - Ifosfamide and gemcitabine: a phase II trial in advanced inoperable non-small
      cell lung cancer.
AB  - The novel nucleoside agent gemcitabine has demonstrated antitumor activity
      against a variety of solid tumors and is associated with low toxicity. A phase I
      trial in Germany of gemcitabine combined with the alkylating agent ifosfamide has
      shown encouraging activity against non-small cell lung cancer. The efficacy and
      toxicity of this combination was further evaluated in a phase II trial involving
      chemotherapy-naive patients with non-small cell lung cancer (mostly stage IV
      disease). Gemcitabine was administered at a dose of 1,000 mg/m2 on days 1, 8, and
      15, followed by a 1-week rest, while ifosfamide was given at a dose of 1,500
      mg/m2 on days 8 through 12. Fifty-five patients were treated, 49 of whom are
      evaluable for response. Six patients were not evaluable because they had not
      received sufficient therapy (less than one complete cycle) because of early
      disease progression or early death. Twelve patients responded, for an overall
      objective response rate of 24.5%. The median survival time was 8.9 months, and
      the 1-year survival rate was 30.9%. Grades 3 and 4 neutropenia occurred in 30.2%
      and 24.5% of patients, respectively, but the incidence of infection was low.
      These results indicate that the combination of gemcitabine and ifosfamide is
      active against non-small cell lung cancer and has a mild toxicity profile, and
      suggest that further evaluation of this combination is warranted.

PMID- 9535207
TI  - Ifosfamide-based three-drug combination regimens in non-small cell lung cancer.
AB  - The role of chemotherapy in the treatment of non-small cell lung cancer (NSCLC)
      has expanded in recent years, resulting in increased median survival and higher 5
      year survival rates in some studies. Few patients with NSCLC can be cured,
      however, and the median survival time is still modest. Research strategies are
      aimed at identifying new active single agents, testing their combination in non
      cisplatin- and non-carboplatin-containing regimens, and their incorporation into
      regimens containing more than two drugs, in efforts to improve response and
      survival and/or reduce toxicity. Several trials of triplet chemotherapy
      combinations for the treatment of NSCLC have been conducted at the University of
      Chicago. The three-drug regimen of vinorelbine, paclitaxel, and ifosfamide with
      granulocyte colony-stimulating factor was evaluated in a phase I trial. Doses of
      all three drugs were reduced from their standard doses so that toxicity would be
      manageable, although toxicity was still high. The low response rate (<20%) at the
      recommended phase II doses led to early closure of this trial. The University of
      Chicago is also assessing the three-drug combination of carboplatin, paclitaxel,
      and ifosfamide in patients with stage IIIB and IV NSCLC. The carboplatin and
      paclitaxel doses are being maintained within their active single-agent range,
      with the goal of identifying the maximum tolerated dose of ifosfamide when added
      to this combination. Additional end points include response rates, survival time,
      and dose-limiting toxicities. This study is ongoing.

PMID- 9535208
TI  - Docetaxel and ifosfamide in patients with advanced solid tumors: results of a
      phase I study.
AB  - Docetaxel is a new antimicrotubule agent that has been shown to be active against
      a variety of solid tumors. Ifosfamide is an alkylating drug that has demonstrated
      activity against non-small cell lung cancer, testicular cancer, breast cancer,
      and soft tissue sarcoma. This phase I study of the combination of these drugs was
      performed to assess the feasibility of using the two agents together, to
      determine the maximum tolerated dose and the side effects, and to propose a safe
      schedule for further phase II studies. Thirty-four patients with histologically
      confirmed solid tumors who had not been treated previously with taxanes or
      ifosfamide and who had received no more than one line of chemotherapy for
      advanced disease were entered into the study. Treatment consisted of docetaxel
      given as a 1-hour infusion followed by ifosfamide as a 24-hour infusion (schedule
      A), or ifosfamide followed by docetaxel (schedule B) every 3 weeks. Docetaxel
      doses ranged from 60 to 85 mg/m2 and ifosfamide doses from 2.5 to 5.0 g/m2.
      Grades 3 and 4 granulocytopenia were observed in 89% of courses and appeared to
      be of short duration and related to the ifosfamide dose. Febrile neutropenia and
      sepsis occurred in 17% and 2% of courses, respectively. Severe anemia and
      thrombocytopenia were uncommon. Nonhematologic toxicities were mild to moderate,
      and included alopecia, nausea, vomiting, mucositis, diarrhea, sensory neuropathy,
      skin and nail toxicity, hypersensitivity reactions, and edema. Schedule B
      appeared to induce more gastrointestinal toxicity than schedule A. One complete
      response in soft tissue sarcoma and two partial responses, one in cancer of
      unknown primary and the other in non-small cell lung cancer, were documented. The
      dose-limiting toxicity for schedule A was neutropenic fever at a dose of 85 mg/m2
      docetaxel and 5 g/m2 ifosfamide. The dose-limiting toxicity for schedule B was
      neutropenic fever at a dose of 75 mg/m2 docetaxel and 4 g/m2 ifosfamide. A dose
      of 75 mg/m2 docetaxel combined with 5 g/m2 ifosfamide according to schedule A can
      be recommended for further studies.

PMID- 9535209
TI  - Ifosfamide and docetaxel in non-small cell lung cancer.
AB  - Ifosfamide has been in use for several decades and is generally considered to be
      one of the most effective drugs for the treatment of non-small cell lung cancer
      (NSCLC). At the same time, docetaxel is one of the new, promising drugs with high
      antitumor activity in various solid tumors. In NSCLC, an objective remission rate
      of 33% could be achieved in chemotherapy-naive patients. Currently, clinical
      research with docetaxel in NSCLC patients focuses on various combinations of this
      drug with radiotherapy and a number of different cytostatic chemicals. There are
      good reasons for combining docetaxel with ifosfamide. In addition to the
      promising antitumor activity in NSCLC displayed by both drugs, it is an advantage
      that docetaxel and ifosfamide have only minimal overlapping nonhematologic
      toxicity. Moreover, the combination seems to be well founded due to the lack of
      cross-resistance between docetaxel and alkylators such as ifosfamide of the
      oxazaphosphorine type, which have shown synergistic antitumor activity in vivo.
      Based on this background, two phase I studies of docetaxel and ifosfamide have
      been initiated.

PMID- 9535210
TI  - Etoposide plus ifosfamide plus cisplatin in the treatment of small cell lung
      cancer.
AB  - Approximately 25% of all lung cancer cases diagnosed in 1993 were due to small
      cell lung cancer (SCLC). Approximately one third of all SCLC patients present
      with limited disease. Efforts to improve treatment results for patients with
      limited-stage SCLC include two recent meta-analyses of combined-modality
      treatment involving chemotherapy with thoracic radiotherapy versus chemotherapy
      alone. Both of these studies showed improvements in survival with the combined
      modality approach. In addition, preliminary results of a Hoosier Oncology Group
      phase II study of cisplatin/ifosfamide/etoposide (VIP) in combination with
      thoracic radiotherapy in patients with limited disease indicate that VIP has an
      acceptable toxicity profile and should be studied further. For patients
      presenting with extensive-stage SCLC, several combination regimens have been
      shown to be effective in inducing responses of approximately 60%, although none
      has established superiority. Results of several studies evaluating the standard
      cyclophosphamide/doxorubicin/vincristine (CAV) regimen versus cisplatin
      containing combination regimens have shown no obvious survival advantage of the
      cisplatin regimens over CAV. On the other hand, results of a Hoosier Oncology
      Group study of VIP versus cisplatin/etoposide in extensive-disease SCLC showed
      that overall survival favored (P = .044) the VIP arm (9.1 months v 7.3 months),
      although these results need to be confirmed in another trial.

PMID- 9535211
TI  - Multimodality treatment including early high-dose chemotherapy with peripheral
      blood stem cell transplantation in limited-disease small cell lung cancer.
AB  - Combined-modality treatment for limited-disease small cell lung cancer using
      conventional chemotherapy and chest irradiation achieves high response rates, but
      most patients relapse over a period of 12 to 16 months. To improve current
      results, we performed a phase II trial including high-dose chemotherapy and
      peripheral blood progenitor cell transplantation (PBPCT) as part of an early
      intensification strategy after two cycles of induction therapy. Moreover, to
      reduce the risk of local recurrence, the protocol included surgical resection in
      stages I to IIIA patients as well as chest irradiation. Between January 1991 and
      July 1994, 16 consecutive patients (median age, 50 years; age range, 30 to 59
      years) were treated in this single-center trial. The patients received two cycles
      of conventional chemotherapy consisting of etoposide 500 mg/m2, ifosfamide 4
      g/m2, cisplatin 50 mg/m2, and epirubicin 50 mg/m2 plus granulocyte colony
      stimulating factor 5 microg/kg at a 3-week interval, followed by PBPC collection
      and subsequent high-dose etoposide 1,500 mg/m2, ifosfamide 12 g/m2, carboplatin
      750 mg/m2, and epirubicin 150 mg/m2 with PBPCT. The duration of the entire
      chemotherapy program was 9 weeks. Six of 10 patients in stages I to IIIA and one
      of six patients in stage IIIB received neoadjuvant or adjuvant surgery before
      high-dose chemotherapy, followed by thoracic (50 Gy) and prophylactic (30 Gy)
      cranial irradiation. Hematopoietic reconstitution after high-dose chemotherapy
      occurred within 11 days (range, 9 to 17 days) for both neutrophils (>0.5 x
      10(9)/L) and platelets (>20 x 10(9)/L). Oral mucositis (World Health Organization
      grade 2 to 4) was the predominant nonhematologic toxicity, which was observed in
      12 of 16 patients. One patient developed neutropenic septicemia with fatal
      multiorgan failure. At a median follow-up of 44 months (range, 32 to 77 months)
      after PBPCT, nine patients are alive and well, resulting in a disease-free and
      overall survival rate of 56.3% +/- 12.4%. The median overall survival has not yet
      been achieved. None of the patients who had surgery relapsed or died after
      therapy. All relapses occurred within the first 12 months after PBPCT. Patients
      in stages I to IIIA (10 patients) had a 70% +/- 14% overall survival rate at 4
      years, while patients in stage IIIB (six patients) had a 33% +/- 19% survival
      rate at 4 years, with a median survival of 17 months posttransplant. These data
      demonstrate that a multimodality treatment including early high-dose chemotherapy
      with PBPCT may lead to a prolonged disease-free survival in the majority of
      patients. A randomized phase III study has now been initiated to prospectively
      investigate the role of high-dose chemotherapy, surgery, and chest irradiation in
      the multidisciplinary approach to limited-disease small cell lung cancer.

PMID- 9535212
TI  - No more excuses! Turning quiet resistance into active advocacy for research.

PMID- 9535214
TI  - Binding to four-way junction DNA: a common property of architectural proteins?
AB  - Proteins that can be shown to strongly bind in vitro to the four-way (Holliday)
      junction DNA include not only the obvious candidates such as enzymes involved in
      recombination, but also a remarkably diverse group of seemingly unrelated
      proteins. These include the HMG1 box proteins, members of the HMGI-Y family,
      winged helix proteins (including linker histones), the SWI/SNF complex, and some
      totally unrelated prokaryotic proteins. What these proteins seem to share is a
      propensity to bind to bent DNA, to bend DNA upon binding, and/or to
      preferentially interact with DNA crossings. Thus, they appear to be, in the main,
      architectural proteins, although some (like the SWI/SNF complex) have very
      specific functional roles as well. Perhaps because they bind to or promote the
      formation of particular DNA structures, the four-way junction binding proteins
      are frequently interchangeable in cellular function. Furthermore, since a given
      kind of structure can be recognized by many different protein motifs, it is not
      surprising that apparently unrelated proteins can fall into such a single
      functional class.

PMID- 9535216
TI  - Aging-associated up-regulation of neuronal 5-lipoxygenase expression: putative
      role in neuronal vulnerability.
AB  - Aging is associated with neurodegenerative processes. 5-Lipoxygenase (5-LO),
      which is also expressed in neurons, is the key enzyme in the synthesis of
      leukotrienes, inflammatory eicosanoids that are capable of promoting
      neurodegeneration. We hypothesized that neuronal 5-LO expression can be up
      regulated in aging and that this may increase the brain's vulnerability to
      neurodegeneration. We observed differences in the distribution of 5-LO-like
      immunoreactivity in various brain areas of adult young (2-month-old) vs. old (24
      month-old) male rats. Greater 5-LO-like immunoreactivity was found in old vs.
      young rats, in particular in the dendrites of pyramidal neurons in limbic
      structures, including the hippocampus, and in layer V pyramidal cells of the
      frontoparietal cortex and their apical dendrites. The aging-increased expression
      of neuronal 5-LO protein appears to be due to increased 5-LO gene expression.
      Using a quantitative reverse transcription/polymerase chain reaction assay and 5
      LO-specific oligonucleotide primers and their mutated internal standards, we
      observed about a 2.5-fold greater hippocampal 5-LO mRNA content in old rats. 5-LO
      like immunoreactivity was also observed in small, nonpyramidal cells, which were
      positive for glutamic acid decarboxylase or glial fibrillary acid protein. This
      type of 5-LO immunostaining did not increase in the old rats. Hippocampal
      excitotoxic injury induced by systemic injection of kainate was greater in old
      rats. Neuroprotection was observed with the 5-LO inhibitor, caffeic acid.
      Together, these results suggest that aging increases both neuronal 5-LO
      expression and neuronal vulnerability to 5-LO inhibitor-sensitive excitotoxicity,
      and indicate that the 5-LO system might play a significant role in the
      pathobiology of aging-associated neurodegenerative diseases.

PMID- 9535213
TI  - Biological responses to electromagnetic fields.
AB  - Electrification in developed countries has progressively increased the mean level
      of extremely low-frequency electromagnetic fields (ELF-EMFs) to which populations
      are exposed; these humanmade fields are substantially above the naturally
      occurring ambient electric and magnetic fields of approximately 10(-4) Vm(-1) and
      approximately 10(-13) T, respectively. Several epidemiological studies have
      concluded that ELF-EMFs may be linked to an increased risk of cancer,
      particularly childhood leukemia. These observations have been reinforced by
      cellular studies reporting EMF-induced effects on biological systems, most
      notably on the activity of components of the pathways that regulate cell
      proliferation. However, the limited number of attempts to directly replicate
      these experimental findings have been almost uniformly unsuccessful, and no EMF
      induced biological response has yet been replicated in independent laboratories.
      Many of the most well-defined effects have come from gene expression studies;
      several attempts have been made recently to repeat these key findings. This
      review analyses these studies and summarizes other reports of major cellular
      responses to EMFs and the published attempts at replication. The opening sections
      discuss quantitative aspects of exposure to EMFs and the incidence of cancers
      that have been correlated with such fields. The concluding section considers the
      problems that confront research in this area and suggests feasible strategies.

PMID- 9535215
TI  - Lipoprotein(a) and lipoprotein profile in healthy centenarians: a reappraisal of
      vascular risk factors.
AB  - In this study we assessed whether widely accepted risk factors for
      atherosclerotic vascular diseases such as lipoprotein(a) [Lp(a)], a cholesterol
      rich lipoprotein under strict genetical control, and other lipid parameters
      change with age. The variations of blood levels and the pathophysiological role
      of Lp(a) in old people, and particularly in the oldest old, are unknown.
      Accordingly, we measured Lp(a) levels as well as total, LDL, and HDL cholesterol
      (CT), and triglycerides (TG) in sera from 75 healthy centenarians, 114 randomly
      selected subjects under 65 years, 73 randomly selected elderly people, and 30
      healthy selected elderly people. The results showed that Lp(a) serum levels did
      not vary by age group, including centenarians. Remarkably, one-quarter of the
      centenarians had high Lp(a) serum levels even though they never suffered from
      atherosclerosis-related diseases. At variance with young and aged people,
      centenarians with high Lp(a) serum levels also had high plasma concentrations of
      the proinflammatory cytokine IL-6, suggesting that genetic control of the Lp(a)
      serum level may attenuate with age and that environmental factors such as chronic
      subclinical inflammatory processes may play a role. We also showed that most
      centenarians are paradoxically characterized by low HDL-CT and relatively high TG
      levels, which together are considered to be strong risk factors for coronary
      heart disease. On the whole, these data support the hypothesis that a continuous
      and complex reshaping of lipid metabolism occurs in physiological aging, likely
      contributing to successful aging.

PMID- 9535217
TI  - Overexpression of HSP-70 inhibits the phosphorylation of HSF1 by activating
      protein phosphatase and inhibiting protein kinase C activity.
AB  - This laboratory reported previously that overexpressed heat shock protein 70 kDa
      (HSP-70) inhibited the activation of its transcriptional factor, HSF1. We had
      conducted experiments to understand the mechanisms whereby HSP-70 down-regulated
      the activation of HSF1. Genetically overexpressed HSP-70 had no effects on the
      HSF1 level in cytosol, but significantly inhibited phosphorylation of HSF1 in the
      nucleus. Transfection of cells with HSF1 cDNA resulted in increases in the
      unphosphorylated, but not phosphorylated, HSF1 levels in both the cytosol and
      nucleus. Because serine phosphorylation of various proteins was reduced in HSP-70
      cDNA-transfected cells, we measured the activity of enzymes involved in serine
      phosphorylation. Overexpressed HSP-70 significantly inhibited the enzymatic
      activities of protein kinase A (PKA by 73 and 62% in the cytosol and membrane
      bound fraction, respectively) and protein kinase C (PKC by 61% in membrane-bound
      fraction), whereas it activated that of protein phosphatase (PP by 33 and 86% in
      the cytosol and the membrane-bound fraction, respectively). Forskolin (a PKA
      stimulator), PMA (a PKC stimulator), and okadaic acid (an inhibitor of PP) were
      used to investigate whether HSP-70-induced changes in PKA, PKC, and PP were
      responsible for the HSF1 dephosphorylation. Forskolin did not change nuclear HSF1
      phosphorylation, suggesting that decreases in PKA activity in HSP-70
      overexpressing cells is not associated with HSF1 phosphorylation. PMA and okadaic
      acid induced an increase in HSF1 phosphorylation in both vector- and HSP-70 cDNA
      transfected cells, although levels of phosphorylated HSF1 in HSP-70 cDNA
      transfected cells were lower than those in vector-transfected cells. The PMA
      induced increase in HSF1 phosphorylation in HSP-70 cDNA-transfected cells was
      blocked by pretreatment with staurosporine, a PKC inhibitor. These results
      suggest that overexpression of HSP-70 inhibits phosphorylation of HSF1 at serine
      residues by activating PP and inhibiting PKC activity.

PMID- 9535218
TI  - Apoptosis caused by oxidized LDL is manganese superoxide dismutase and p53
      dependent.
AB  - Oxidized low density lipoprotein (oxLDL) induces apoptosis in human macrophages
      (Mphi), a significant feature in atherogenesis. We found that induction of
      apoptosis in Mphi by oxLDL, C2-ceramide, tumor necrosis factor alpha (TNF-alpha),
      and hydrogen peroxide (H2O2) was associated with enhanced expression of manganese
      superoxide dismutase (MnSOD) and p53. Treatment of cells with p53 or MnSOD
      antisense oligonucleotides prior to stimulation with oxLDL, C2-ceramide, TNF
      alpha, or H2O2 caused an inhibition of the expression of the respective protein
      together with a marked reduction of apoptosis. Exposure to N-acetylcysteine
      before treatment with oxLDL, C2-ceramide, TNF-alpha, or H2O2 reversed a decrease
      in cellular glutathione concentrations as well as the enhanced production of p53
      and MnSOD mRNA and protein. In apoptotic macrophages of human atherosclerotic
      plaques, colocalization of MnSOD and p53 immunoreactivity was found. These
      results indicate that in oxLDL-induced apoptosis, a concomitant induction of p53
      and MnSOD is critical, and suggest that it is at least in part due to an
      enhancement of the sphingomyelin/ceramide pathway.

PMID- 9535219
TI  - A novel protein complex involved in signal transduction possessing similarities
      to 26S proteasome subunits.
AB  - A novel protein complex has been identified in human cells that has a molecular
      mass of approximately 450 kDa. It consists of at least eight different subunits
      including JAB1, the Jun activation-domain binding protein 1, and Trip15, the
      thyroid hormone receptor-interacting protein 15. The purified complex contains
      COP9 and COP11 protein homologs and is very similar, if not identical, to the
      plant COP9 complex involved in light-mediated signal transduction. The isolated
      JAB1-containing particle has kinase activity that phosphorylates IkappaBalpha,
      the carboxy terminus of p105, and Ser63 and/or Ser73 of the amino-terminal
      activation domain of c-Jun. The phosphorylation of c-Jun requires the carboxy
      terminus of the protein containing the DNA binding and dimerization domains.
      Three subunits of the new complex--Sgn3, Sgn5/JAB1, and Sgn6--exhibit sequence
      similarities to regulatory components of the 26S proteasome, which could indicate
      the existence of common substrate binding sites. Immunofluorescence staining
      reveals that the new complex shows a subcellular distribution similar to that of
      the 26S proteasome. The functional relationship of the two particles in
      regulating transcriptional activity is discussed. Considering the putative role
      of the complex in signal transduction and its widespread occurrence, we suggest
      the name JAB1-containing signalosome.

PMID- 9535220
TI  - Rescue of cells from apoptosis by inhibition of active GSH extrusion.
AB  - Cells induced to apoptosis extrude glutathione in the reduced form concomitantly
      with (U937 cells) or before (HepG2 cells) the development of apoptosis, much
      earlier than plasma membrane leakage. Two specific inhibitors of carrier-mediated
      GSH extrusion, methionine or cystathionine, are able to decrease apoptotic GSH
      efflux across the intact plasma membrane, demonstrating that in these cell
      systems GSH extrusion occurs via a specific mechanism. While decreasing GSH
      efflux, cystathionine or methionine also decrease the extent of apoptosis. They
      fail to exert anti-apoptotic activity in cells previously deprived of GSH,
      indicating that the target of the protection is indeed GSH efflux. The cells
      rescued by methionine or cystathionine remained viable after removal of the
      apoptogenic inducers and were even able to replicate. This shows that a real
      rescue to perfect viability and not just a delay of apoptosis is achieved by
      forcing GSH to stay within the cells during apoptogenic treatment. All this
      evidence indicates that extrusion of reduced glutathione precedes and is
      responsible for the irreversible morphofunctional changes of apoptosis, probably
      by altering the intracellular redox state without intervention of reactive oxygen
      species, thus giving a rationale for the development of redox-dependent apoptosis
      under anaerobic conditions.

PMID- 9535222
TI  - Double-stranded DNA can be translocated across a planar membrane containing
      purified mitochondrial porin.
AB  - The transport of genetic material across biomembranes is a process of great
      relevance for several fields of study. However, much remains to be learned about
      the mechanisms underlying transport, one of which implies the involvement of
      proteic DNA-conducting pores. Entry of genetic material into mitochondria has
      been observed under both physiological and pathological conditions. We report
      here that double-stranded DNA can move through a planar bilayer membrane
      containing isolated mitochondrial porin (voltage-dependent anion channel). The
      transport is driven by the applied electrical field, and the presence of DNA is
      associated with a decrease of current conduction by the pores. The passage of DNA
      does not take place if the bilayer has not been doped with any protein or in the
      presence of both reconstituted porin and anti-porin antibody. Translocation does
      not occur if the bilayer contains Shigella sonnei maltoporin, gramicidin A
      channels, or a 30 pS anion-selective channel plus other proteins. These results
      show that mitochondrial porin is capable of mediating the transport of genetic
      material, revealing a new property of this molecule and further confirming the
      idea that DNA can move through proteic pores.

PMID- 9535221
TI  - Lipoxin B4 regulates human monocyte/neutrophil adherence and motility: design of
      stable lipoxin B4 analogs with increased biologic activity.
AB  - Lipoxins are biologically active products of arachidonic acid that are formed via
      cell-cell interactions, particularly those involving leukocytes. Lipoxin A4 and
      lipoxin B4 (LXB4), within similar concentration ranges, each inhibit human
      neutrophil, activate monocyte adherence and motility, and are rapidly converted
      by initial dehydrogenation to other inactive metabolites by human monocytes.
      Here, we exposed LXB4 to isolated recombinant 15-hydroxy-prostaglandin
      dehydrogenase (15-PGDH) and found that it was a good substrate for the enzyme
      (Km=6.9 microM); we identified the major product as 5-oxo-LXB4 via physical
      methods including liquid chromatography/tandem mass spectrometry. This is the
      first evidence of 15-PGDH converting a substrate hydroxyl group at a position
      other than the omega-6 carbon. Based on these observations, several LXB4 analogs
      were designed and prepared by total organic synthesis to test as stable mimetics:
      5(S)-methyl-LXB4-me, 5(R)-methyl-LXB4-me, and 15-epi-LXB4-me (the aspirin
      triggered form of LXB4). Both 5(S)-methyl-LXB4-me and 5(R)-methyl-LXB4-me were
      resistant to rapid conversion. In addition, actions of the stable analogs were
      evaluated separately with human mono-cytic cells and neutrophils, and 5(S)-methyl
      LXB4-me was more potent (nM range) than LXB4 for both cell types. In contrast,
      5(R)-methyl-LXB4-me was potent in inhibiting neutrophil transmigration across
      endothelial monolayers, but did not stimulate monocyte adherence. These results
      indicate that LXB4 analogs can be designed to resist rapid transformation and
      retain bioactivity with both monocytes and neutrophils. Moreover, they suggest
      that LXB4 stable analogs are useful tools to selectively evaluate the modes of
      actions of LXB4 with different tissues.

PMID- 9535223
TI  - RNA-directed amino acid homochirality.
AB  - The phenomenon of L-amino acid homochirality was analyzed on the basis that
      protein synthesis evolved in an environment in which ribose nucleic acids
      preceded proteins, so that selection of L-amino acids may have arisen as a
      consequence of the properties of the RNA molecule. Aminoacylation of RNA is the
      primary mechanism for selection of amino acids for protein synthesis, and models
      of this reaction with both D- and L-amino acids have been constructed. It was
      confirmed, as observed by others, that the aminoacylation of RNA by amino acids
      in free solution is not predictably stereoselective. However, when the RNA
      molecule is constrained on a surface (mimicking prebiotic surface monolayers), it
      becomes automatically selective for the L-enantiomers. Conversely, L-ribose RNA
      would have been selective for the D-isomers. Only the 2' aminoacylation of
      surface-bound RNA would have been stereoselective. This finding may explain the
      origin of the redundant 2' aminoacylation still undergone by a majority of
      today's amino acids before conversion to the 3' species required for protein
      synthesis. It is concluded that L-amino acid homochirality was predetermined by
      the prior evolution of D-ribose RNA and probably was chirally directed by the
      orientation of early RNA molecules in surface monolayers.

PMID- 9535224
TI  - Community-based nursing practice: necessary but not sufficient.

PMID- 9535225
TI  - Actions taken by nursing education programs in the United States to prevent
      tuberculosis transmission in nursing students.
AB  - Measures to prevent tuberculosis include education and skin testing of at-risk
      groups, including health care workers. This study focused on policies and
      practices related to tuberculosis in nursing education programs, especially skin
      testing and instruction. Data were collected from a stratified random sample of
      nursing administrators in associate and baccalaureate degree programs in the
      United States using an instrument adapted from a medical school study. Several
      factors may have contributed to fewer skin test conversions in nursing programs
      than in medical schools. Although most nursing education programs considered skin
      testing a priority, there were inconsistencies related to skin testing type and
      process when compared with recent Centers for Disease Control and Prevention
      guidelines. Major content gaps related to multidrug-resistant tuberculosis and
      the differences between pulmonary and extrapulmonary symptomatology were found.

PMID- 9535226
TI  - The changing environment of community health practice and education: perceptions
      of staff nurses, administrators, and educators.
AB  - Historically, baccalaureate nursing programs in Canada have prepared graduates to
      practice in the community. Two recent trends-the move to prepare all registered
      nurses in degree programs and the changing climate in which community nursing is
      practiced-made it timely to explore the educational preparation required for
      community health practice. This article reports on one part of the study, i.e.,
      on findings that explicate the nature of community health nursing practice in a
      western Canadian province, as it has changed during the past decade, as it is
      currently practiced, and as it is expected to develop in the future. What, in
      other words, is the nature of the community practice for which nursing students
      should be prepared? An action research design guided the study. Participants were
      recruited from all major urban, rural, and northern settings in which
      baccalaureate nurses practice throughout the province. The perspective of
      relevant people was considered important, i.e., nurses practicing in the
      community, administrators, and educators of future community nurses. One hundred
      eighteen (118) participants were interviewed in 27 focus groups. Data were tape
      recorded, transcribed, and analyzed for content. Among the themes identified were
      those that captured changes community health nurses experienced in their nursing
      practice. Nurses also described how they thought practice would evolve in the
      years to come. These themes are discussed within a primary health care framework
      in which nurses can be expected to play a more active role in shaping community
      health nursing practice.

PMID- 9535228
TI  - Evaluation of service learning in a school of nursing: primary care in a
      community setting.
AB  - The evolving system of health care delivery, emphasizing prevention and early
      intervention, presents challenges to schools that educate health care
      professionals. Nursing faculty in a rural mid-Atlantic state initiated a service
      learning project, relating education and service through primary care in the
      surrounding community. The purpose of the present study was to evaluate the
      project outcomes. The 45 students involved in the project responded to Beliefs
      Related to Professional Nursing Competencies, a quantitative measure (Cronbach's
      alpha = .84), based on the Pew Health Commission's "Competencies Needed by
      Practitioners for 2005," and to a second measure, Qualitative Questions for
      Students in Service Learning. Results of quantitative analysis revealed subjects'
      acceptance of the competencies as nursing responsibilities. Qualitative analysis
      revealed that students were involved in increasing consumer access to community
      based primary care; curricula relating learning to existing problems and
      rewarding critical thinking was evident; and students were receiving preparation
      for a health care environment that will rely on their ability to respond to its
      changing needs.

PMID- 9535227
TI  - Transforming the curriculum while serving the community: strategies for
      developing community-based sites.
AB  - Developing community-based clinical opportunities for students is a challenge. At
      San Jose State University (SJSU) School of Nursing, faculty transformed the
      curriculum by developing community-based experiences directed by faculty and
      delivered by students during clinical practice. These innovative clinical
      experiences provide a structure to educate students and enhance the ability to
      bring health care to underserved people in a community. This article describes
      the structure and processes for implementing the new experiences and offers
      strategies to guide other faculty interested in developing community-based
      experiences.

PMID- 9535229
TI  - Community partnerships: redirecting the education of undergraduate nursing
      students.
AB  - Consistent with the goal of reforming nursing education to support nursing's
      agenda for health care reform, a community-based, multiprofessional initiative
      supported by the W.K. Kellogg Foundation began in Hawaii in 1991. This initiative
      created a partnership among the University of Hawaii Schools of Medicine,
      Nursing, Social Work, and Public Health, three community health centers, and
      their communities to provide a community-based, integrated system of health care,
      education, and research. In response to this initiative, the School of Nursing
      developed an integrated undergraduate curriculum consisting of: a discipline
      specific tutorial using an inquiry-based learning strategy; a multiprofessional
      tutorial; and a 1-year clinical experience providing culturally competent primary
      care. Community-based education has stimulated changes in the philosophy,
      mission, and curriculum of the School of Nursing. The outcomes achieved as a
      result of this initiative have had a favorable impact on clients using the
      community health centers, the communities, the School of Nursing, and the
      students.

PMID- 9535230
TI  - A Veterans Affairs facility provides independent home health clinical experiences
      with a case manager focus.

PMID- 9535231
TI  - Problem-based learning: preparing post-RN students for community-based care.

PMID- 9535232
TI  - Community clinical sites for psychiatric nursing students.

PMID- 9535233
TI  - Primary Health Care and partnerships: collaboration of a community agency, health
      department, and university nursing program.
AB  - Health care reform proposals emphasize health care that is essential, practical,
      scientifically sound, coordinated, accessible, appropriately delivered, and
      affordable. One route to achievement of improved health outcomes within these
      parameters is the formation of partnerships. Partnerships adopting the philosophy
      and five principles of Primary Health Care (PHC) focus on health promotion and
      prevention of illness and disability, maximum community participation,
      accessibility to health and health services, interdisciplinary and intersectoral
      collaboration, and use of appropriate technologies such as resources and
      strategies. A community service agency serving a multicultural population
      initiated a partnership with a health department and a university undergraduate
      nursing program. The result was a preschool health fair and there were benefits
      for each partner-benefits which could not have been realized without the
      collaboration. The health fair partnership planning, implementation, and
      evaluation process was guided by a framework shaped by the philosophy and five
      principles of PHC. The educational process described can be applied to other
      learning experiences where the goal is to help students understand and apply the
      concepts of PHC, develop myriad nursing competencies, and form collaborative
      relationships with the community and health agencies. Community health care
      dilemmas and nursing education challenges can be successfully addressed when
      various disciplines and sectors form effective partnerships.

PMID- 9535234
TI  - Quantitative analysis and classification of gait patterns in cerebral palsy using
      a three-dimensional motion analyzer.
AB  - Gait disorders in cerebral palsy can be accurately analyzed using the CODA-3
      system presenting quantitative data representing movement of the hip, knee, and
      ankle in the sagittal plane. We describe a technique that classifies abnormal
      gait automatically on the basis of sagittal kinematic data. Fifty-five hemiplegic
      and 91 diplegic patients were analyzed using an opto-electronic scanner (CODA-3).
      The sagittal kinematics of the affected limb in hemiplegics correlated with those
      of both affected limbs in diplegics. We introduce the concept of the "plegic
      limb." Sagittal kinematics of 237 affected limbs were studied using cluster
      statistical analysis. Eight clear groups emerged. The predominant clinical
      features, typical of each group, were identified and described (eg, stiff leg
      gait, genu recurvatum, or crouch gait). We propose this classification system as
      a new technique to use gait analysis data to automatically classify abnormal
      movements of the lower limb in cerebral palsy.

PMID- 9535235
TI  - Drug therapy in juvenile dermatomyositis: follow-up study.
AB  - A series of 33 patients with juvenile dermatomyositis was reviewed in terms of
      their prognosis in relation to their drug therapy. This retrospective study was
      intended to help clarify the use of various therapies in this rare, heterogeneous
      disease from our hospital's experience in the last 24 years. The results
      confirmed that oral corticosteroids should remain the undisputed first line of
      treatment. For more refractory, chronic patients, the results suggest that
      azathioprine should be the favored drug of first choice (in addition to
      corticosteroids). There may be a role for cyclosporine as a "rescue" treatment,
      but this needs to be further defined.

PMID- 9535236
TI  - Acute-phase neurologic complications of Haemophilus influenzae type b meningitis:
      association with developmental problems at school age.
AB  - The purposes of this study were to describe the incidence of acute-phase
      neurologic complications in a sample of 126 children with Haemophilus influenzae
      type b meningitis, and to determine if these complications were associated with
      higher rates of learning and behavior problems at school age. Risks were assessed
      by comparing rates of adverse psychoeducational outcomes in the 53 children in
      the sample with complications to corresponding outcome rates in the 67 children
      who were free of neurologic complications and who did not have abnormal
      electroencephalograms (EEGs) or computed tomographic (CT) scans. Comparisons were
      made by means of logistic regression analysis. Twenty-nine children (23% of the
      sample) had seizures, 16 (13%) were comatose or obtunded, 15 (12%) had
      sensorineural hearing loss, 8 (6%) had hemiparesis, and 7 (6%) had cranial nerve
      deficits other than hearing loss. Relative to children without complications,
      those with complications had higher rates of grade repetition and substandard
      performance on neuropsychological and achievement testing. Adverse outcomes,
      however, consisted primarily of more subtle cognitive and learning problems; only
      two of the children in the sample obtained prorated IQ scores below 70. Sequelae
      were associated with persistent neurologic deficits and bilateral hearing loss,
      as well as with transient symptoms including seizures, coma, and hemiparesis.
      While study findings argue against adverse consequences for the vast majority of
      children treated for this disease, the results clarify learning and behavior
      outcomes and indicate which children are at greatest risk.

PMID- 9535238
TI  - Molecular basis of genetic heterogeneity: role of the clinical neurologist.
AB  - Advances in molecular genetics have disclosed many different explanations for
      allelic heterogeneity, how different clinical syndromes arise from mutations in
      the same gene. The converse, how similar clinical syndromes arise from mutations
      of different genes on different chromosomes is called locus heterogeneity. Both,
      however, give rise to some disease-defining mutations, as in childhood spinal
      muscular atrophy or Duchenne muscular dystrophy. Nevertheless, new problems have
      been created, including what might be called "diagnosis by the number," diverse
      syndromes from mutations in the same gene without current explanation, or
      siblings with different clinical syndromes. These discoveries have transformed
      the clinical neurology of heritable diseases. They also provide clinicians with
      new responsibilities and opportunities in defining clinical syndromes and
      influencing the evolution of our clinical language.

PMID- 9535237
TI  - Cavum septi pellucidi and cavum vergae in normal and developmentally delayed
      populations.
AB  - Recent studies have shown that the persistence of the cavum septi pellucidi
      beyond the neonatal period is a marker of cerebral dysgenesis. It has been
      suggested that the finding of a persistent cavum vergae is also a marker of
      disturbed brain development. In order to investigate this hypothesis we reviewed
      161 brain magnetic resonance imaging scans from normal individuals for the
      presence of cavum septi pellucidi or cavum vergae, or both. In the 34
      prospectively obtained normal adults, there were no individuals with either a
      cavum septi pellucidi or cavum vergae. In the "defined" normal subjects 3 of 127
      individuals (2.4%) had a cavum septi pellucidi whereas a cavum vergae was noted
      in 26 of 127 (20.5%). We next reviewed the neuroimaging studies of 249 children
      and adults evaluated for mental retardation or developmental delay. A cavum septi
      pellucidi was found in 38 of 249 (15.3%) and a cavum vergae in 48 of 249 (19.3%)
      of these patients. A cavum septi pellucidi and cavum vergae were found together
      in 19 of 249 (7.6%). We interpret these data as showing that the cavum septi
      pellucidi is rarely seen in normal individuals although the cavum vergae is seen
      with the same frequency in normal and retarded populations. Thus we conclude that
      the cavum septi pellucidi serves as a significant marker of cerebral dysfunction
      manifested by neurodevelopmental abnormalities while the cavum vergae alone does
      not identify individuals at risk for cognitive delays.

PMID- 9535239
TI  - Immature teratoma of the leptomeninges in an 8-year-old child: unusual
      presentation with recurrent transient oculomotor nerve palsies and rapid
      progression to diffuse brain infarction.

PMID- 9535240
TI  - Single high-dose intravenous immunoglobulin for treatment of pediatric Guillain
      Barre syndrome.

PMID- 9535241
TI  - Commentary on human hippocampal structures: re: Braak et al.

PMID- 9535242
TI  - Selective use of vancomycin to prevent coagulase-negative staphylococcal
      nosocomial bacteremia in high risk very low birth weight infants.
AB  - OBJECTIVE: To determine whether vancomycin added to parental nutrition (PN)
      fluids could prevent nosocomial infections in very low birth weight newborns and
      which infants would benefit most from prophylaxis. DESIGN: Double blind,
      randomized controlled study. SETTING AND STUDY POPULATION: Very low birth weight
      infants receiving PN in a tertiary neonatal intensive care unit. METHODS: Thirty
      eight infants with and without central vascular catheters were randomized to
      receive no medication or 25 microg/ml vancomycin added to PN for the duration of
      the infant's PN requirements. RESULTS: The addition of 25 microg/ml vancomycin to
      PN prevented bacteremia in very low birth weight infants receiving PN. There was
      a significant reduction in the number of coagulase-negative staphylococcal (CONS)
      bacteremias (defined as isolation of the same organism from two positive blood
      cultures) during PN (5 vs. 0; P = 0.037) as well as the total number of
      bacteremias and fungemias (9 vs. 1; P = 0.036). The total number of hospital days
      (108 +/- 13 vs. 76 +/- 6; P = 0.039) were reduced in infants receiving
      vancomycin. Infants with birth weights of < 1000 g who received corticosteroids
      for treatment of chronic lung disease benefitted most from treatment. No
      vancomycin-resistant strains of CONS or enterococci were detected during the
      study period. CONCLUSIONS: Prophylactic treatment with vancomycin effectively
      prevented CONS bacteremia under the conditions of the study. Its use was most
      effective in infants with birth weights of <1000 g.

PMID- 9535243
TI  - An investigation of vancomycin-resistant Enterococcus faecium within the
      pediatric service of a large urban medical center.
AB  - BACKGROUND: Between 1990 to 1992 and 1993 to 1995 there was a >5-fold increase
      (16.7% to 89.8%) in vancomycin-resistant Enterococcus faecium isolates as a
      percentage of all isolates of vancomycin-resistant enterococci on the pediatric
      units of The New York Hospital-Cornell Medical Center (NYH-CMC). A molecular
      epidemiologic investigation was undertaken to determine the extent to which this
      increase was associated with the spread of a vanA-containing clone of vancomycin
      resistant E. faecium that had been previously defined in adults hospitalized at
      NYH-CMC or with the spread of another vanA clone that had been defined in
      children hospitalized on the pediatric service at Memorial Sloan-Kettering Cancer
      Center, which shares a common pediatric intensive care unit and pediatric house
      staff with NYH-CMC. METHODS: Molecular genotyping of vancomycin-resistant E.
      faecium isolates obtained from pediatric patients from 1993 to 1995 was performed
      by pulsed field gel electrophoresis of chromosomal SmaI digests. Southern
      hybridization was performed using vanA- and vanB-specific probes. Medical records
      of patients were reviewed for pertinent clinical and demographic information.
      RESULTS: A single vanB clone of vancomycin-resistant E. faecium was responsible
      for 17 (77.3%) of 22 isolates in the neonatal intensive care unit (NICU) of NYH
      CMC. Two other vanB strains of vancomycin-resistant E. faecium and 2 vanA strains
      were identified among the 5 remaining NICU isolates. Vancomycin-resistant E.
      faecium isolates from the other pediatric units represented a heterogeneous
      population of primarily vanA strains, but vanA clonal strains previously
      identified from patients on adult services at NYH-CMC and from children
      hospitalized at Memorial Sloan-Kettering Cancer Center were not detected.
      CONCLUSION: A newly identified vanB clone was responsible for the increase in
      vancomycin-resistant E. faecium isolates in the NICU of NYH-CMC. The increase of
      vancomycin-resistant E. faecium among children hospitalized at NYH-CMC was
      unrelated to the spread of vancomycin-resistant E. faecium among adults in the
      same hospital or among children at an affiliated facility cared for by the same
      house staff and sharing a common pediatric intensive care unit.

PMID- 9535245
TI  - Immunization of children with pertussis toxoid decreases spread of pertussis
      within the family.
AB  - OBJECTIVE: In a previously reported double blind placebo-controlled trial it was
      shown that vaccination with pertussis toxoid during infancy reduced the incidence
      of pertussis in the vaccinees. Parents and siblings of participants in the trial
      were followed for pertussis to determine whether vaccination provided indirect
      protection of close contacts in a nonvaccinating country with a high incidence of
      pertussis. STUDY DESIGN: A group of 3450 infants were randomized to vaccination
      with diphtheria, tetanus and pertussis toxoids (DTPtxd) or to diphtheria and
      tetanus toxoids (DT). Pertussis cases were actively sought and diagnosed by
      cultures and serology in vaccinees (previously reported) and in family members
      during 2 years after the third vaccination. RESULTS: Pertussis as defined by the
      World Health Organization (paroxysmal cough of > or = 21 days and certain
      laboratory criteria) was diagnosed in 11 parents of DTPtxd recipients and in 26
      parents of DT recipients; indirect protection was 60% (95% confidence intervals,
      16 to 82%). In nonvaccinated younger siblings of DTPtxd and DT recipients there
      were 10 and 18 cases of pertussis, respectively; indirect protection was 43% (95%
      confidence intervals, -31 to 76%). When all cases of pertussis with cough > or =
      7 days were included, the indirect protection was 44% (95% confidence intervals,
      7 to 67%) in parents and 56% (95% confidence intervals, 9 to 81%) in younger
      siblings. CONCLUSION: Vaccination of children with pertussis toxoid reduces
      spread of pertussis to close contacts, which suggests that mass vaccination with
      pertussis toxoid would induce herd immunity.

PMID- 9535244
TI  - Neurocognitive abnormalities in children after classic manifestations of Lyme
      disease.
AB  - BACKGROUND: In adults a subtle encephalopathy characterized primarily by memory
      impairment, irritability and somnolence may occur months to years after classic
      manifestations of Lyme disease. However, only limited information is available
      about whether there is an equivalent disorder in children. METHODS: Case series
      of five children seen in a Lyme disease clinic in a university referral center
      for evaluation of neurocognitive symptoms that developed near the onset of
      infection or months after classic manifestations of Lyme disease. The diagnosis
      was based on clinical symptoms, serologic reactivity to Borrelia burgdorferi and
      intrathecal antibody production to the spirochete. Evaluation included detailed
      neuropsychologic testing. After evaluation the children were treated with
      intravenous ceftriaxone for 2 or 4 weeks. Follow-up was done in the clinic and a
      final assessment was made by telephone 2 to 7 years after treatment. RESULTS:
      Along with or months after erythema migrans, cranial neuropathy or Lyme
      arthritis, the five children developed behavioral changes, forgetfulness,
      declining school performance, headache or fatigue and in two cases a partial
      complex seizure disorder. All five patients had IgG antibody responses to B.
      burgdorferi in serum as well as intrathecal IgG antibody production to the
      spirochete. Two patients had CSF pleocytoses and three did not. Despite normal
      intellectual functioning the five children had mild to moderate deficits in
      auditory or visual sequential processing. After ceftriaxone therapy, the four
      children in whom follow-up information was available experienced gradual
      improvement in symptoms. CONCLUSIONS: Children may develop neurocognitive
      symptoms along with or after classic manifestations of Lyme disease. This may
      represent an infectious or postinfectious encephalopathy related to B.
      burgdorferi infection.

PMID- 9535246
TI  - Safety and immunogenicity of the Towne strain cytomegalovirus vaccine.
AB  - BACKGROUND: Women with naturally acquired serum antibodies to cytomegalovirus
      (CMV) are usually protected against both frequent secondary infection and giving
      birth to infants severely affected by intrauterine CMV infection. OBJECTIVE: To
      determine the feasibility of using a live attenuated strain of CMV (Towne) to
      achieve immunity similar to that provided by wild-type infection, we evaluated a
      new lot of the Towne strain of CMV in 3 open label trials involving 68 men, 63
      women of childbearing age and 13 children, respectively. RESULTS: Mild local
      reactions occurred among approximately one-third of subjects. There were no
      systemic reactions. All 45 subjects tested developed lymphoproliferative
      responses to CMV. CD8+ class I-restricted cytotoxic T cell responses specific for
      CMV antigens were detected in three of four subjects and persisted for 6 months.
      Neutralizing titers were maximal at 2 to 4 months postimmunization, were dose
      dependent and were comparable to those induced by natural infection. CONCLUSION:
      These results support further evaluation of the Towne strain of CMV in women at
      risk for acquiring CMV infection during pregnancy or among children transmitting
      CMV to pregnant women.

PMID- 9535247
TI  - Diphtheria, tetanus and whole cell pertussis vaccine combined with hepatitis B
      vaccines: a comparison of two doses (10 microg and 5 microg).
AB  - BACKGROUND: A combined diphtheria-tetanus-whole cell pertussis-hepatitis B
      (DTPwHB) vaccine might facilitate the achievement of universal vaccination of
      infants against hepatitis B. METHODS: A double blind, randomized, two-armed,
      single center study was undertaken to evaluate the immunogenicity and
      reactogenicity of combined tetravalent DTPwHB vaccine, with two dosages of
      hepatitis B component (10 microg and 5 microg). The combined vaccine was tested
      in the context of a simplified vaccination schedule at 1.5, 3.5 and 6 months of
      age, to 120 healthy infants born to hepatitis B surface antigen-negative mothers
      after priming with one dose of hepatitis B vaccine (10 microg) at birth.
      Antibodies to each antigenic component were measured from blood samples collected
      immediately after birth, pre- and postvaccination blood samples. RESULTS: The
      reactogenicity profiles were similar in the two groups. No serious adverse events
      were reported. One month after completion of the four-dose vaccination schedule,
      all subjects except one in Group 1 (10 microg) had protective titers of anti-HBs
      (10 mIU/ml). At this time the geometric mean titer in Group 1 (10 microg) was
      higher than that observed in Group 2 (5 microg), 696 vs. 488 mIU/ml (P = 0.19).
      One month after three doses all subjects in both groups had protective
      antidiphtheria titers and antitetanus titers. The vaccine response rate to the
      Bordetella pertussis component of the vaccine was 88.0% in Group 1 and 96.2% in
      Group 2 (P = 0.86). CONCLUSION: Both combined tetravalent vaccines are safe and
      immunogenic when administered to infants born to a hepatitis B surface antigen
      negative mother, with a 10-microg dose of priming hepatitis B vaccine at birth.
      This combined tetravalent DTPwHB vaccine may play an important role to promote
      integration of HB vaccine into the Expanded Program of Immunization in hepatitis
      B-endemic areas.

PMID- 9535248
TI  - Streptococcus pneumoniae capsular polysaccharide-diphtheria toxoid conjugate
      vaccine is immunogenic in early infancy and able to induce immunologic memory.
AB  - BACKGROUND: Pneumococcal polysaccharide vaccines are not protective against the
      most common pneumococcal infections in infancy. The importance of pneumococcal
      diseases and emerging antimicrobial resistance emphasize the need for
      prophylaxis. METHODS: Pneumococcal conjugate vaccine, containing capsular
      polysaccharides from serotypes 6B, 14, 19F and 23F conjugated to diphtheria
      toxoid (PncD), was given to 75 infants at 2, 4 and 6 months of age. Three dosages
      (1, 3 or 10 microg of each) were used. A placebo group of 49 infants received
      physiologic saline. Children were given a booster dose of either polysaccharide
      or conjugate vaccine at 14 months of age; the placebo group received conjugate
      vaccine. Antibody concentrations were determined with an enzyme immunoassay.
      RESULTS: The highest dose induced the strongest response after primary
      immunization, but booster response was greatest in the group primed with the
      lowest dose. Polysaccharide and conjugate vaccines induced booster responses of
      the same magnitude. At 24 and 36 months of age the antibody concentrations were
      similar in children who had received the PncD in infancy and in children
      immunized at 14 months of age only. CONCLUSIONS: The PncD conjugate vaccine is
      immunogenic and able to induce immunologic memory.

PMID- 9535250
TI  - The clinical spectrum of respiratory syncytial virus disease in The Gambia.
AB  - BACKGROUND: Respiratory syncytial virus (RSV) is a well-recognized cause of lower
      respiratory tract infections in early childhood in industrialized countries, but
      less is known about RSV infection in developing countries. METHODS: Four
      outbreaks of RSV infection that occurred between 1993 and 1996 in The Gambia,
      West Africa, were studied. RSV was sought by immunofluorescent staining of
      nasopharyngeal aspirate samples among young children who presented with
      respiratory infections at three hospitals in the Western Region of the country.
      RESULTS: Five hundred seventy-four children with RSV infection were identified.
      The median ages of children seen in 1993 through 1996 were 3, 7, 8 and 5 months,
      respectively. Sixty-two percent of children <6 months old were boys. Thirteen
      children (2.4%) had conditions considered to increase the risk of severe RSV
      infection. On physical examination crepitations were heard in 80% of the children
      admitted to hospital, whereas wheezes were heard in only 39%. Eighty (16%)
      children received oxygen because of hypoxemia. Nine of 255 blood cultures (3.5%)
      were positive: 4 Streptococcus pneumoniae; 2 Haemophilus influenzae type b; 2
      Staphylococcus aureus; and 1 Enterobacter agglomerans. Thirteen children died
      (2.4%). During the 4 study years 90, 25, 75 and 95% of isolates typed were RSV
      Subgroup A, respectively. CONCLUSIONS: RSV is a significant cause of lower
      respiratory tract infection in young children in The Gambia, causing epidemics of
      bronchiolitis. It poses a significant burden on the health system, especially
      through the demand for supplementary oxygen. The clinical spectrum of RSV disease
      in The Gambia is similar to that seen in developed countries; concomitant
      bacterial infections are uncommon.

PMID- 9535251
TI  - Sepsis evaluations in hospitalized infants with bronchiolitis.
AB  - OBJECTIVES: To define variation in the decision to perform a sepsis evaluation in
      hospitalized infants with bronchiolitis, to define predictors of the decision and
      to measure the clinical and cost outcomes. METHODS: Retrospective chart review of
      all nonintensive care unit infants < or = 60 days with any discharge diagnosis of
      bronchiolitis (n = 282 from 1993 to 1995 in a 232-bed pediatric hospital. Process
      variables included temperature at sepsis work-up or Tmax if no sepsis workup.
      Outcome variables were charges, length of stay, sepsis workup and serious
      bacterial infection. RESULTS: There was no difference in mean temperature between
      groups with or without sepsis evaluation (38.1 degrees C, P = 0.75). Of 282
      infants 140 had a sepsis workup; 5 (1.8%) had serious bacterial infection.
      Infants with sepsis workup had an average total charge of $4507 and length of
      stay of 3.4 days compared with $2998 and 2.8 days for those without (P = 0.0001
      and P = 0.002, respectively). A multivariate logistic regression model was
      constructed with sepsis workup as the dichotomous dependent variable. Significant
      (P < or = 0.05) predictor variables with a positive coefficient were: higher
      bronchiolitis score and normal chest roentgenogram. Significant variables with a
      negative coefficient were: admission diagnosis of bronchiolitis, chest
      roentgenogram typical for bronchiolitis and age > 28 days. CONCLUSIONS:
      Temperature was not a predictor of sepsis evaluation. Infants with respiratory
      distress and normal chest roentgenogram were more likely to receive sepsis
      evaluations; those with recognized typical bronchiolitis and those > 28 days of
      age were less likely. Risk of serious bacterial infection is low; the costs of a
      sepsis evaluation outweigh the benefits in infants with obvious bronchiolitis.

PMID- 9535254
TI  - HIV viral load.

PMID- 9535253
TI  - Interferon-alpha treatment of chronic hepatitis C virus infection in children.
AB  - OBJECTIVES: To determine the safety and efficacy of interferon-alpha therapy of
      chronic hepatitis C virus (HCV) infection in children. STUDY DESIGN: This was an
      open-labeled prospective trial of interferon-alpha-2a (IFN-alpha) in children
      with evidence of HCV infection for at least 6 months. Twenty-three children were
      enrolled and treated with IFN-alpha at a dosage of 3 million units/m2 three times
      weekly. Beginning in 1995 patients defined as complete or partial responders
      after 6 months were offered an additional 6 months of treatment. Endpoints were
      alanine aminotransferase normalization and loss of hepatitis C viral ribonucleic
      acid from serum. Responders were compared with nonresponders for age, gender,
      duration of infection, pretreatment alanine aminotransferase and hepatitis C
      viral ribonucleic acid levels, saturation of serum iron-binding capacity,
      histologic score of chronic hepatitis and viral genotype. Statistical methods
      used for these comparisons included the Kruskal-Wallis test, the Mann-Whitney two
      sample test and the Fisher exact test. RESULTS: Of the 21 children who completed
      at least 6 months of treatment, 4 (19%) had complete response, 8 (38%) had
      partial response and 9 (43%) had no response. Three of the 4 complete responders
      had prolonged treatment; in 2 the response was maintained. One responder relapsed
      but responded to a second, longer course of treatment. Four of the 8 partial
      responders had prolonged therapy and 3 of them became complete responders. One
      child who was originally a nonresponder lost HCV RNA within the first year after
      therapy. Thus eventually 7 (33%) of 21 patients were complete responders. After
      at least 12 months of follow-up on most of these children, no relapses have been
      observed. No differences in any of the variables tested could be demonstrated
      between responders and nonresponders, but small sample size limits power. IFN
      alpha was discontinued in only one child because of side effects, and temporary
      dosage adjustments were needed in 4 children. CONCLUSIONS: IFN-alpha is of some
      efficacy in the treatment of chronic HCV infection in children. Complete or
      partial responders at 6 months should undergo prolonged treatment.

PMID- 9535249
TI  - Sequential annual administration of purified fusion protein vaccine against
      respiratory syncytial virus in children with cystic fibrosis.
AB  - BACKGROUND: We recently showed the clinical benefit of the PFP-2 vaccine for
      respiratory syncytial virus (RSV) for children with cystic fibrosis (CF).
      OBJECTIVE: To determine the safety and immunogenicity of yearly sequential
      administration of the PFP-2 vaccine in CF children. STUDY DESIGN: Twenty-nine of
      the 34 CF children who participated in the previous study were enrolled in this
      open label vaccine study. All of the CF children ages 2.6 to 8.9 years received
      the PFP-2 vaccine, the PFP/PFP group received the PFP-2 vaccine in 1993 and 1994
      and the saline/PFP group received the vaccine for the first time in 1994. At
      entry demographic data and measurements of lung function and nutrition were
      collected. Microneutralization test, enzyme-linked immunosorbent assay to F
      protein and Western blot assay were performed on plasma drawn before and 4 weeks
      after vaccination and at the end of the RSV season. During the study weekly
      telephone calls were made and acute respiratory illnesses were evaluated.
      RESULTS: Baseline measurements were similar between groups. Systemic and local
      vaccine reactions were mild and similar for both groups. A 4-fold or greater
      neutralizing antibody rise to RSV occurred in 4 of 14 (28.6%) and 9 of 14 (64.3%)
      in PFP/PFP and saline/PFP groups (P = 0.13), respectively. Four children in the
      PFP/PFP group and 7 in the saline/PFP group were infected with RSV. A reduction
      in lower respiratory illnesses (1.0 vs. 2.0), antibiotic courses (2.5 vs. 5.6)
      and days of illnesses (37.3 vs. 93.1) was observed in the PFP/PFP vaccinees
      infected with RSV compared with the saline/PFP group (t test; P < or = 0.05). One
      death occurred in the PFP/PFP group; the cause of death was consistent with
      septic shock and unrelated to vaccination or RSV infection. CONCLUSION:
      Sequential annual PFP-2 vaccination was safe and not associated with exaggerated
      respiratory disease.

PMID- 9535252
TI  - Plasma glutathione concentrations in children infected with human
      immunodeficiency virus.
AB  - BACKGROUND: Glutathione (GSH) is the principal intracellular defense against
      oxidants, and HIV-infected individuals tend to have subnormal concentrations in
      plasma. This GSH deficiency may contribute to the pathogenesis of disease
      progression. In the pediatric population correlations between GSH concentrations
      with clinical, immunologic and virologic disease profiles are scarce. OBJECTIVES:
      The main objectives of this study were (1) to compare plasma GSH concentrations
      of HIV-infected children and healthy controls and (2) to correlate GSH values
      with clinical, immunologic and virologic disease indices. METHODS: Twenty-four
      HIV-infected and 24 healthy control children entered the study. Plasma
      concentrations of total glutathione and related thiols were determined. RESULTS:
      The difference in mean plasma GSH concentrations between HIV-infected (2.96 +/-
      0.31 microM) and control (6.62 +/- 0.58 microM) groups was highly significant (P
      < 0.0001). Linear regression analyses in HIV-infected patients revealed
      significant correlations between GSH and both absolute CD4+ cell counts (r =
      0.56, P = 0.004) and viral load measured as log HIV-RNA PCR (r = -0.49, P =
      0.018). GSH concentrations did not significantly correlate with CDC clinical
      stage but were lower in HIV-infected patients with growth failure (1.60 +/- 0.54
      microM) vs. non-growth failure (3.23 +/- 0.33 microM); P = 0.05. CONCLUSIONS:
      This study confirmed that HIV-infected children are deficient in plasma GSH
      concentrations compared with healthy controls. We documented that low GSH
      concentrations in HIV-infected children are directly correlated with CD4+ cell
      counts and inversely correlated with viral loads. These findings support a
      possible role of GSH in the pathogenesis of HIV disease progression.

PMID- 9535255
TI  - Varicella vaccine.

PMID- 9535256
TI  - Meropenem.

PMID- 9535257
TI  - Use of Guthrie cards for the early diagnosis of neonatal herpes simplex virus
      disease.

PMID- 9535258
TI  - Invasive antibiotic-resistant Streptococcus pneumoniae in children in Madrid.

PMID- 9535259
TI  - Monthly prevalence of group A, B and G Streptococcus, Haemophilus influenzae
      types E and F and Pseudomonas aeruginosa nasopharyngeal colonization in the first
      two years of life.

PMID- 9535260
TI  - Postexposure varicella vaccination in siblings of children with active varicella.

PMID- 9535261
TI  - Neonatal tinea capitis.

PMID- 9535263
TI  - Meningococcal vaccine in pregnancy: an assessment of infant risk.

PMID- 9535262
TI  - Penetration of ceftriaxone into the middle ear fluid of children.

PMID- 9535264
TI  - Persistent fever, Pseudomonas pneumonia and gram-negative septicemia in a three
      year-old male child.

PMID- 9535265
TI  - Guillain-Barre syndrome in a child with serologic evidence of Borrelia
      burgdorferi infection.

PMID- 9535266
TI  - Acyclovir and related compounds.

PMID- 9535267
TI  - Should we be treating oral thrush?

PMID- 9535268
TI  - Application of the Rochester Criteria in febrile neonates.

PMID- 9535269
TI  - Environmental effects on disulfide bonding patterns of bovine kappa-casein.
AB  - Bovine kappa-casein, the stabilizing protein of the colloidal milk protein
      complex, has a unique disulfide bonding pattern. The protein exhibits varying
      molecular sizes on SDS-PAGE ranging from monomer to octamer and above in the
      absence of reducing agents. Heating the samples with SDS prior to electrophoresis
      caused an apparent decrease in polymeric distribution: up to 60% monomer after 30
      min at 90 degrees C as estimated by densitometry of SDS-PAGE. In contrast,
      heating the samples without detergent at 90 or 37 degrees C caused a significant
      increase in high-molecular-weight polymers as judged by electrophoresis and
      analytical ultracentrifugation. In 6 M urea, the protein could be completely
      reduced, but upon dialysis, varying degrees of polymer reformation occurred
      depending on the dialysis conditions. Spontaneous reoxidation to polymeric forms
      is favored at low pH (<5.15) and low ionic strength. The results are discussed
      with respect to the influence of the method of preparation on the polymer size of
      kappa-caseins and on their resultant physical chemical properties.

PMID- 9535270
TI  - Electrospray ionization mass spectrometric study of the multiple intracellular
      monomeric and polymeric hemoglobins of Glycera dibranchiata.
AB  - The intracellular hemoglobin (Hb) of the marine polychaete Glycera dibranchiata
      is comprised of two groups of globins differing in their primary structures and
      state of aggregation. About six electrophoretically and chromatographically
      distinct monomeric Hbs which have Leu as the distal residue, and an equal number
      of polymeric Hbs which have the usual distal His, have been identified to date.
      Deconvolution of the electrospray ionization mass spectra (ESI-MS) of the Hbs and
      of their carbamidomethylated, reduced, and reduced/carbamidomethylated forms,
      using a maximum entropy-based approach (MaxEnt), showed the presence of at least
      18 peaks attributable to monomer Hbs (14,500-15,200 Da) and an approximately
      equal number of polymer Hb peaks (15,500-16,400 Da). Although the ratio of the
      monomer to polymer components in pooled Hb preparations remained constant at
      60:40, Hb from individuals had generally less than 6 monomer and 6 polymer
      components; -2 of the 19 individuals appeared to be deficient in polymer Hbs.
      Taking into account possible fragmentations of the known monomeric and polymeric
      globin sequences, we estimate conservatively that there are 10 monomeric and an
      equal number of polymeric Hbs, the majority comprising a single free Cys.
      Surprisingly, the calculated mass of the sequence deduced from the high
      resolution monomer Hb crystal structures does not correspond to any of the
      observed masses. ESI-MS of the monomer Hb crystal revealed 11 components, of
      which 5, accounting for 67% of total, were related to the three major sequences
      GMG2-4. These findings underline the need for routine mass spectrometric
      characterization of all protein preparations. The complete resolution of the
      Glycera Hb ESI-MS using MaxEnt processing illustrates the power of this method to
      resolve complex protein mixtures.

PMID- 9535271
TI  - Inhibitory effect of magnesium ion on the human placental alkaline phosphatase
      catalyzed reaction in a reverse micellar system.
AB  - Human placental alkaline phosphatase is a membrane-anchored protein. Entrapping
      the enzyme into a reverse micellar vesicle mimics the in vivo conditions and
      allows examination of the properties of the enzyme. Placental alkaline
      phosphatase is enzymatically active in Aerosol-OT/isooctane reverse micelles.
      Substantially different kinetic behavior of the enzyme has been observed in
      aqueous or reverse micellar systems. In aqueous solution, Mg2+ is a nonessential
      activator of the enzyme. In the experiments described in the present report Mg2+
      was found to be an inhibitor for the enzyme in reverse micelles. This inhibition
      is presumably due to a time-dependent conformational change of the enzyme
      molecule, which resulted in a curvature in the recorder tracings of the enzyme
      assays. The Mg2+-induced conformational change of the enzyme was completely
      prevented by phosphate and partially reserved by EDTA. High concentrations of
      Zn2+ also strongly inhibited enzyme activity in both aqueous and reverse micellar
      solvent systems, presumably by occupying the Mg2+ (M3) site of the enzyme.
      However, binding of Zn2+ at the M3 site did not cause conformational change of
      the enzyme and the enzyme assay tracing was linear. The M3 site of the enzyme is
      proposed to have a modulatory role in vivo using magnesium ion as the modulator.

PMID- 9535272
TI  - Two novel alpha-neurotoxins isolated from Taiwan cobra: sequence characterization
      and phylogenetic comparison of homologous neurotoxins.
AB  - Two novel postsynaptic neurotoxins (alpha-neurotoxins) isolated and purified from
      the Taiwan cobra venom (Naja naja atra) possess distinct primary sequences and
      different neurotoxicities as compared with the most abundant and lethal component
      in the venom, i.e., cobrotoxin characterized before from the same venom. The
      complete sequences of two neurotoxin analogues were determined by N-terminal
      Edman degradation and comparison of amino acid compositions of proteolytic toxin
      fragments with other homologous toxins of known sequences. The short-chain
      neurotoxin consists of 61 amino acid residues with eight conserved cysteine
      residues and is found to show 78% sequence identity with cobrotoxin. The other
      toxin, consisting of 65 residues with ten cysteines, belongs to the family of
      long-chain neurotoxins. It is the first long-chain alpha-neurotoxin reported from
      the Taiwan cobra. The lethal toxicities of these two novel neurotoxins were much
      lower than cobrotoxin, albeit with close structural homology among the three
      toxins in terms of their primary sequences and tertiary structure predicted by
      homology modeling. Multiple sequence alignment and comparison coupled with
      construction of a phylogenetic tree for various alpha-neurotoxins of Naja and
      closely related genuses have established that all nicotinic alpha-neurotoxins
      present in the snake family of Elapidae are closely related to each other,
      presumably derived from an ancestral polypeptide by gene duplication and
      subsequent multiple mutational substitutions.

PMID- 9535274
TI  - Molecular modeling of cytochrome P450 2B1: mode of membrane insertion and
      substrate specificity.
AB  - A molecular model of a mammalian membrane-bound cytochrome P450, rat P450 2B1,
      was constructed in order to elucidate its mode of attachment to the endoplasmic
      reticulum and the structural basis of substrate specificity. The model was
      primarily derived from the structure of P450BM-3, which as a class II P450 is the
      most functionally similar P450 of known structure. However, model development was
      also guided by the conserved core regions of P450cam and P450terp. To optimally
      align the P450 2B1 and P450BM-3 sequences, multiple alignment was performed using
      sequences of five P450s in the II family, followed by minor adjustments on the
      basis of secondary structure predictions. The resulting P450 2B1 homology model
      structure was refined by molecular dynamics heating, equilibration, simulation,
      and energy minimization. The model suggests that the F-G loop serves as both a
      hydrophobic membrane anchor and entrance channel for hydrophobic substrates from
      the membrane to the P450 active site. To assess the mode of substrate binding,
      benzphetamine, testosterone, and benzo[a]pyrene were docked into the active site.
      The hydrophobic substrate-binding pocket is consistent with the preferences of
      this P450 toward hydrophobic substrates, while the presence of an acidic Glu-105
      in this pocket is consistent with the preference of this P450 for the cationic
      substrate benzphetamine. This model is thus consistent with several known
      experimental properties of this P450, such as membrane attachment and substrate
      selectivity.

PMID- 9535273
TI  - The binding of benzopyranes to human serum albumin. A structure-affinity study.
AB  - The binding of several benzopyranes to serum albumin was studied by equilibrium
      dialysis at pH 7.4 in a 67 mM sodium phosphate buffer at 37 degrees C. The
      equilibrium data were analyzed using a computer program for curve fitting. The
      binding isotherm for warfarin, 4-hydroxycoumarin, 4-chromanol, coumarin, 3
      acetylcoumarin, and benzoic acid can be described by two stoichiometric
      dissociation constants. Elimination of the 4-hydroxyl group in the coumarin
      chemical structures decreases the binding affinity of the compounds on the
      primary binding site of serum albumin, with 4-chromanol the smallest ligand which
      binds to seroalbumin with high affinity. Thus, the affinity of 4-benzopyranol and
      the 4-hydroxybenzopyranones greater than that of benzopyranones. On the other
      hand, elimination of the 2-oxo group in the benzopyranone chemical structures
      decreases affinity for the secondary binding site.

PMID- 9535275
TI  - Studies of the M15 beta-galactosidase complementation process.
AB  - M15 beta-Galactosidase was activated by heat-denatured wild-type beta
      galactosidase, urea, and heat-denatured wild-type beta-galactosidase, a peptide
      made up of residues 6-44 of beta-galactosidase and CB2, the peptide that is
      normally used for complementation (residues 3-92 of beta-galactosidase). In each
      case roughly equal activation levels were attained. Heat-denatured wild-type beta
      galactosidase was present as a finely divided visible white precipitate both
      before and after complementation. The heat-denatured protein by itself did not
      migrate on native PAGE and both the protein and the activity that occurred as a
      result of the complementation also remained at the point of application. The N
      terminal ends of the heat-denatured wild-type beta-galactosidase must have been
      available for complementation and must have been mobile enough to allow tetramer
      to form despite being aggregated. Beta-galactosidase denatured by both urea and
      heat resulted in a streak of interacting protein on the native PAGE. Upon
      activation, a streak (indicating that interaction was still occurring) was still
      present, but it moves more slowly. Complementation using a peptide called XP
      (made up of residues 6-44 plus an additional nine C-terminal amino acids)
      resulted in three discrete forms of active enzyme at ratios of peptide to M15
      beta-galactosidase monomer of less than 1:1. The fastest migrating of the three
      bands predominated at ratios near 1:1. A single active tetrameric form of M15
      beta-galactosidase was formed with CB2. In both of these last two cases an active
      slow-moving diffuse band also formed (possibly a dimer of the tetramer). A
      quantitation of the amount of peptide bound to M15 beta-galactosidase by
      titration with XP and with CB2 and by using gel filtration after an excess of
      fluorescent-labeled XP was added showed that peptide bound in a 1:1 ratio
      (peptide/monomer) when full activity was achieved. These fluorescent studies also
      showed that peptide initially bound to dimer and that the tetramer was then
      formed.

PMID- 9535276
TI  - Isolation and characterization of full and truncated forms of human breast
      carcinoma protein BA46 from human milk fat globule membranes.
AB  - We have isolated and characterized two proteins of 50 and 30 kDa from human milk
      fat globule membranes of healthy donors. N-terminal and internal sequencing
      revealed that the 50-kDa protein is the full-length human breast carcinoma
      protein BA46 that is highly expressed in human breast tumors. The 30-kDa protein
      is a truncated form of protein BA46 which consists of the C-terminal factor
      V/VIII-like domain of BA46 and which appears to anchor BA46 to the milk fat
      globule membrane. Defective release of the epidermal growth factor domain
      containing a surface RGD motif may be related to involvement of BA46 in breast
      cancer.

PMID- 9535277
TI  - The tryptophan fluorescence of Tetracarbidium conophorum agglutinin II and a
      solution-based assay for the binding of a biantennary glycopeptide.
AB  - The plant lectin Tetracarbidium conophorum agglutinin II binds to glycoproteins
      and glycopeptides in a structurally specific manner [Animashaun et al., (1994)
      Glycoconjugate J. 11, 299-303]. We have characterized the steady-state and time
      resolved fluorescence of the tryptophan residues of this lectin. The fluorescence
      (lambda[ex] = 295 nm, lambda[em] = 350 nm) decay is complex and can be described
      by four decay times with the following values: tau1 = 7.4 nsec, alpha1 = 0.22;
      tau2 = 2.9 nsec, alpha2 = 0.25: tau3 = 1.0 nsec, alpha3 = 0.34, tau4 = 0.2 nsec,
      alpha4 = 0.18. The addition of a biantennary glycopeptide (carbohydrate sequence
      [see text]) to the lectin results in a quench and an 8 nm blue shift of the
      emission spectrum. The effect is saturable, and is described by an association
      constant of 1.8 x 10(5) M(-1). The tryptophan fluorescence of Tetracarbidium
      conophorum agglutinin II may therefore be utilized to characterize
      thermodynamically the binding interactions between this lectin and complex
      glycoprotein.

PMID- 9535278
TI  - High-pressure effects on vacuolar H+-ATPase from etiolated mung bean seedlings.
AB  - A high-hydrostatic-pressure technique was employed to study the structure
      function relationship of plant vacuolar H+-ATPase from etiolated mung bean
      seedlings (Vigna radiata L.). When isolated vacuolar H+-ATPase was subjected to
      hydrostatic pressure, the activity of ATP hydrolysis was markedly inhibited in a
      time-, protein concentration- and pressure-dependent manner. The pressure
      treatment decreased both Vmax and Km of solubilized vacuolar H+-ATPase, implying
      an increase in ATP binding affinity, but a decrease in the ATP hydrolysis
      activity. Physiological substrate, Mg2+-ATP, augmented the loss of enzymatic
      activity upon pressure treatment. However, ADP, AMP, and Pi exerted substantial
      protective effects against pressurization. Steady-state ATP hydrolysis was more
      sensitive to pressurization than single-site ATPase activity. The inactivation of
      solubilized vacuolar H+-ATPase by pressure may result from changes in protein
      protein interaction. The conformational change of solubilized vacuolar H+-ATPase
      induced by hydrostatic pressure was further determined by spectroscopic
      techniques. The inhibition of vacuolar H+-ATPase under pressurization involved at
      least two steps. Taken together, our work indicates that subunit-subunit
      interaction is crucial for the integrity and the function of plant vacuolar H+
      ATPase. It is also suggested that the assembly of the vacuolar H+-ATPase complex
      is probably not random, but follows a sequestered pathway.

PMID- 9535279
TI  - The glycoprotein character of multiple forms of Aspergillus polygalacturonase.
AB  - Comparisons of known primary structures of polygalacturonases show that extent
      and localization of potential N-glycosylation sites differ. Some sites are
      similar in position and adjacent to strictly conserved residues at the potential
      active site. The presence of N-acetylglucosamine and mannose in the molecules of
      two homogeneous, major Aspergillus sp. polygalacturonase forms was confirmed by
      IR spectroscopy. The purification method, based on interaction of the
      carbohydrate part with concanavalin A immobilized on chlorotriazine bead
      cellulose, was optimized. Deglycosylation with N-glycosidase F under denaturating
      and nondenaturating conditions led to molecular mass decreases followed by
      complete inactivation of the polygalacturonase enzyme activity. These results
      show the importance of glycosylation in these protein forms, while the
      comparative patterns establish both variability and some similarities in overall
      glycosylation architectures.

PMID- 9535280
TI  - The changing role of duplex scan in the management of carotid bifurcation disease
      and endarterectomy.
AB  - The development of carotid duplex scanning revolutionized the diagnosis of
      carotid artery disease. Continued advances in the technology as well as
      widespread experience with cartoid ultrasound have redefined the role this
      technology plays in the care of patients with carotid atherosclerosis. Recent
      clinical trials have shown the efficacy of carotid endarterectomy for both
      symptomatic and asymptomatic carotid artery stenosis, but benefit was shown at
      different degrees of stenosis from commonly used duplex diagnostic criteria.
      Investigators have therefore refined duplex diagnostic criteria to conform with
      the randomized trials while also redefining the effect of contralateral
      occlusions. These refined criteria have not only facilitated surgeons' clinical
      recommendations but allowed the performance of carotid surgery without the risks
      and expenses of arteriography. In addition, a better understanding of the
      significance of intraoperative duplex findings and the implications for
      restenosis has increased the utility of duplex scanning during surgery while
      decreasing the frequency of postoperative follow-up. Finally, this review
      discusses a few developing applications of carotid duplex scanning.

PMID- 9535281
TI  - Which asymptomatic patients should have carotid endarterectomy?
AB  - Carotid endarterectomy for asymptomatic very-high-grade stenosis has been shown
      to be of clear benefit when compared with best medical treatment in recent
      prospective randomized studies. However, the benefit of carotid endarterectomy in
      these trials has been less than most vascular surgeons predicted based on prior
      nonrandomized studies. Furthermore, vascular surgeons often see patients who do
      not fit the inclusion criteria for any of the prospective randomized trials and
      whose potential benefit from endarterectomy may be different from that observed
      in those trials. Medical comorbidities or other patient characteristics that
      suggest even small increases in risk for carotid endarterectomy may negate the
      marginal benefit of the procedure in asymptomatic patients. Potential benefit is
      also highly dependent on surgeon-specific and hospital-specific perioperative
      morbidity and mortality. This article addresses some of the factors that may
      alter the potential benefit of carotid endarterectomy and the implications with
      respect to recommendations for or against carotid endarterectomy in the
      individual patient.

PMID- 9535282
TI  - The timing of carotid endarterectomy after acute stroke.
AB  - Evidence exists that carotid artery endarterectomy prevents a second stroke in
      those patients who initially present with a stroke. However, the timing of the
      operation is controversial. Some authors advise a delay of 6 weeks, and others
      recommend an early endarterectomy as soon as the patient is clinically stable.
      The clinical studies addressing this problem are retrospective and nonrandomized,
      providing no definite answers. But they do provide some guidance. It is probably
      safe to perform early endarterectomy in clinically stable patients with negative
      computed tomography (CT) scans. Delay is recommended for more serious
      neurological events with positive CT scans. Early operation may also be indicated
      in patients with a significant threatening carotid arterial lesion.

PMID- 9535283
TI  - Patching with carotid endarterectomy: when to do it and what to use.
AB  - This is an analysis of published data on the outcomes of carotid endarterectomy
      patch reconstruction with the commonly used materials--autologous greater
      saphenous vein, Dacron, and polytetrafluoroethylene. Taken individually, these
      prospective randomized, prospective nonrandomized, and retrospective studies have
      mixed findings with respect to both the advantage of patching over primary
      closure and the superiority, if any, of one patch material. A major problem with
      these reports is small sample size and the associated low statistical power of
      tests on outcomes. Comparative outcomes are often marginally statistically
      significant or not significant at the .05 level. However, when the data from
      similarly designed studies are pooled, as with a meta-analysis, the sample sizes
      are large enough to allow definitive statistical evaluation. This analysis
      indicates that obligatory patching or selectively patching more than 90% of
      carotid endarterectomies gives clearly superior outcomes (in terms of early
      postoperative thrombosis, perioperative stroke, and 50% or more residual or
      restenosis in the first year) when compared with primary closure. There is
      softer, but clearly important, evidence that carotid endarterectomy patch
      reconstruction with greater saphenous vein has better perioperative stroke and
      restenosis outcomes than that obtained with Dacron and polytetrafluoroethylene.

PMID- 9535284
TI  - Recurrent carotid stenosis: prevention, surveillance, and management.
AB  - Carotid endarterectomy has come under closer scrutiny, perhaps more than any
      other surgical procedure. Many studies have shown excellent early results;
      however, recurrent carotid stenosis is a recognized complication arising in the
      postoperative follow-up period. The local and systemic factors that may
      contribute to recurrent stenosis are reviewed. The results of noninvasive
      postoperative surveillance are examined, and a rational schedule is proposed.
      Finally, the diagnosis of recurrent stenosis and its surgical management with
      redo endarterectomy are discussed.

PMID- 9535285
TI  - Carotid and coronary disease: staged or simultaneous management?
AB  - Up to 12% of patients presenting for coronary bypass have critical carotid
      disease, and more than 50% of patients presenting for carotid endarterectomy have
      significant coronary disease. Patients requiring surgery for both carotid and
      coronary disease may be managed with carotid endarterectomy followed by coronary
      bypass (staged approach), with coronary bypass followed by carotid endarterectomy
      (reversed staged approach), or with simultaneous coronary bypass-carotid
      endarterectomy. There are no compelling data proving superiority of any of these
      three approaches. The staged approach is usually associated with lower stroke
      rates but higher myocardial infarction and mortality rates; the reversed staged
      approach with higher stroke rates but lower myocardial infarction and mortality
      rates; and the simultaneous approach with intermediate stroke, myocardial
      infarction, and mortality rates. Unfortunately, reported series vary widely in
      stroke and mortality rates because of wide variability in patient selection
      criteria, especially for simultaneous procedures. Management decisions in these
      patients should be based on the relative severity of their carotid and coronary
      lesions. Management guidelines are discussed in detail.

PMID- 9535286
TI  - Fast tracking carotid endarterectomy: practical considerations.
AB  - The diagnosis-related groups (DRG) and managed care economics have encouraged
      physicians to be more cost and resource efficient. In response to this demand, a
      fast track program for elective carotid endarterectomies has been established at
      Sewickley Valley Hospital. The essential components of this four-step program are
      operation based on duplex ultrasonography alone, same-day admission, a short
      recovery room stay to limit intensive care use, and discharge on the first
      postoperative day. Overall, 79% of patients for elective carotid endarterectomy
      successfully completed all four steps of the protocol at our institution. This
      has resulted in marked cost savings.

PMID- 9535287
TI  - Carotid stenting versus carotid endarterectomy: update on the controversy.
AB  - Carotid stenting has been a controversial subject from the outset. This
      discussion examines three areas: What is the basis for clinical investigation of
      carotid stenting? How do the results seem to compare with current surgical
      practice? Are there important things we do not know about carotid stenting? Does
      carotid stenting produce equal or better stroke prevention over a significant
      period than conventional therapy? Is the short-term morbidity, both neurological
      and general, better than with carotid endarterectomy? Does carotid stenting
      reduce cost? The results of recent series of carotid endarterectomy, some from
      National Institutes of Health (NIH)-funded randomized studies with peer-reviewed
      data, others from large referral centers or large regional experiences, and the
      results of several single-institution case series of carotid stenting that are
      reported in complete manuscript form are summarized. At least four industry
      sponsored trials of carotid stent technology use are being undertaken in the
      United States as of the fall of 1997. Considering that angioplasty and stenting
      in other vessels has been used in many thousands of patients for over a decade,
      it is surprising that some basic issues are not resolved more clearly than they
      seem to be. Specifically in relation to the carotid lesion, seven questions are
      posed that frame some controversial aspects of the role of carotid stenting in
      stroke prevention.

PMID- 9535288
TI  - Transgenic and transcriptional studies on neurosecretory cell gene expression.
AB  - 1. Studies of the regulation of neurosecretory cell gene expression suffer from
      the lack of suitable cell lines. Two approaches have been used to overcome this
      deficit: transfection of neuropeptide genes into heterologous cell lines and
      generation of transgenic animals. 2. Studies with heterologous cell lines have
      revealed the potential involvement of nuclear hormone receptors, POU proteins,
      and fos/jun/ATF family members in the regulation of the vasopressin and oxytocin
      genes. Although limited in their scope, these studies have contributed greatly to
      the dissection of basic properties of elements in the vasopressin and oxytocin
      gene promoters. 3. Transgenic mice, and more recently rats, have been used to
      elucidate genomic regions governing cell specificity and physiological regulation
      of neurosecretory gene expression. The genes encoding the neuropeptides
      vasopressin and oxytocin have been used in many transgenic studies, due to the
      well-defined expression patterns and physiology of the endogenous neuropeptides.
      Cell-specific and physiologically regulated expression of these transgenes has
      been achieved, demonstrating the action of putative repressor elements and
      regulation of the expression of one gene by sequences present in the other gene.
      4. Appropriate expression and translation of transgenes have resulted in the
      production of several useful systems. Expression of oncogene sequences in
      gonadotropin-releasing hormone neurons has allowed the development of cell lines
      from the resulting tumors, overproduction of corticotropin-releasing factor has
      produced animal models of anxiety and obesity, and directed ectopic expression of
      growth hormone has generated a potentially useful rat model of dwarfism. These
      and other animal models of human disease will provide important avenues for the
      development of therapeutic strategies.

PMID- 9535289
TI  - Structure-function relationships of the vasopressin prohormone domains.
AB  - 1. In this review the structure-function relationships of the different
      vasopressin prohormone domains are dated and discussed, with special reference to
      the neurophysin and glycopeptide domains. 2. The primary structures of the
      currently known neurophysins and glycopeptide sequences are compared and
      discussed. 3. The hormone-binding and aggregational properties of neurophysin are
      reviewed and related to a possible function within the regulated secretory
      pathway. 4. It is proposed, based on the properties reviewed here as well as our
      own data shown here, that the sorting of the vasopressin prohormone is initiated
      by hormone binding, which triggers aggregation of the prohormone into the
      characteristic dense cores of the regulated secretory pathway. 5. This may
      suggest that prohormone sorting into the regulated secretory pathway is, in
      general, determined by noncovalent, intramolecular interactions that promote
      aggregation.

PMID- 9535290
TI  - Regulation of the biosynthesis of large dense-core vesicles in chromaffin cells
      and neurons.
AB  - 1. The proteins of large dense-core vesicles (LDV) in neuroendocrine tissues are
      well characterized. Secretory components comprise chromogranins and
      neuropeptides. Intrinsic membrane proteins include cytochrome b-561,
      transporters, SV2, synaptotagmin, and synaptobrevin. 2. The effects of
      stimulation and of second messengers on the biosynthesis of LDV have been studied
      in detail. 3. Regulation of biosynthesis is complex. The cell can adapt to
      prolonged stimulation either by producing vesicles of normal size filled with a
      higher quantum of secretory peptides or by forming larger vesicles. In addition,
      some components, e.g., enzymes, can be upregulated specifically.

PMID- 9535291
TI  - Molecular diversity in neurosecretion: reflections on the hypothalamo
      neurohypophysial system.
AB  - 1. The diversity of molecules involved in various aspects of neurosecretion, such
      as proprotein processing, axonal transport of large dense core vesicles (LDCVs),
      and regulated secretion, is discussed in the context of the hypothalamo
      neurohypophysial system (HNS). 2. Recent studies have uncovered a family of at
      least seven processing enzymes known as proprotein convertases (PCs) which are
      involved in proteolytically cleaving protein precursors at paired basic amino
      acid motifs to yield biologically active peptides. Three of these, PC1(3), 2, and
      5, are found in neurons and are involved in producing regulated secretory peptide
      products. 3. The axonal transport of LDCVs occurs on microtubule tracks by still
      unknown mechanisms. There are over 11 distinct kinesin-related molecules that
      have now been identified as possible microtubule motor candidates. 4. Calcium
      channels in the nervous system are known to be derived from at least five alpha
      subunit and four beta-subunit genes with multiple alternatively spliced isoforms
      in each case. These could account, in part, for the varied calcium currents found
      in the HNS. 5. The large number of proteins and isoforms now demonstrated to be
      involved in regulated secretion are discussed, with a focus on LDCV compositions
      and the synaptotagmin gene family.

PMID- 9535293
TI  - Antibacterial peptides are present in chromaffin cell secretory granules.
AB  - 1. Antibacterial activity has recently been associated with the soluble matrix of
      bovine chromaffin granules. Furthermore, this activity was detected in the
      contents secreted from cultured chromaffin cells following stimulation. 2. The
      agents responsible for the inhibition of Gram+ and Gram- bacteria growth are
      granular peptides acting in the micromolar range or below. In secretory granules,
      these peptides are generated from cleavage of chromogranins and proenkephalin A
      and are released together with catecholamines into the circulation. 3.
      Secretolytin and enkelytin are the best characterized; these two peptides share
      sequence homology and similar antibacterial activity with insect cecropins and
      intestinal diazepam-binding inhibitor. For some of the peptides derived from
      chromogranin A, posttranslational modifications were essential since
      antibacterial activity was expressed only when peptides were phosphorylated
      and/or glycosylated. 4. The significance of this activity is not yet understood.
      It may be reminiscent of some primitive defense mechanism or may serve as a first
      barrier to bacteria infection during stress, as these peptides are secreted along
      with catecholamines.

PMID- 9535292
TI  - Multifactorial modulation of TRH metabolism.
AB  - 1. Thyrotropin releasing hormone (TRH), synthesized in the paraventricular
      nucleus of the hypothalamus (PVN), is released in response to physiological
      stimuli through median eminence nerve terminals to control thyrotropin or
      prolactin secretion from the pituitary. 2. Several events participate in the
      metabolism of this neuropeptide: regulation of TRH biosynthesis and release as
      well as modulation of its inactivation by the target cell. 3. Upon a
      physiological stimulus such as cold stress or suckling, TRH is released and
      levels of TRH mRNA increase in a fast and transient manner in the PVN; a
      concomitant increase in cfos is observed only with cold exposure. 4. Hypothalamic
      cell cultures incubated with cAMP or phorbol esters show a rise in TRH mRNA
      levels; dexamethasone produces a further increase at short incubation times. TRH
      mRNA are thus controlled by transsynaptic and hormonal influences. 5. Once TRH is
      released, it is inactivated by a narrow specificity ectoenzyme, pyroglutamyl
      peptidase II (PPII). 6. In adenohypophysis, PPII is subject to stringent control:
      positive by thyroid hormones and negative by TRH; other hypothalamic factors such
      as dopamine and somatostatin also influence its activity. 7. These combined
      approaches suggest that TRH action is modulated in a coordinate fashion.

PMID- 9535294
TI  - Factors governing activity-dependent structural plasticity of the
      hypothalamoneurohypophysial system.
AB  - 1. The adult hypothalamoneurohypophysial system (HNS) undergoes reversible
      morphological changes in response to physiological stimulation. 2. In the
      hypothalamus, stimulation of neurohormone secretion results in reduced astrocytic
      coverage of oxytocinergic somata and dendrites so that their surfaces become
      directly juxtaposed. Concurrently, there is a significant increase in the number
      of GABAergic, glutamatergic. and noradrenergic synapses impinging on the neurons.
      3. In the neurohypophysis, stimulation induces retraction of pituicyte processes
      from the perivascular area and enlargement and multiplication of neurosecretory
      terminals. 4. These neuronal-glial and synaptic changes are reversible with
      cessation of stimulation, thus rendering the HNS an excellent model to study
      physiologically linked structural neuronal plasticity in the adult CNS. 5. We
      still do not know the cellular mechanisms and factors underlying such plasticity.
      Recent studies indicate, however, that the adult HNS expresses molecular
      characteristics normally associated with histogenesis and/or tissue
      reorganization in developing or regenerating neural systems. They include
      expression of cell adhesion molecules such as the highly sialylated isoform of
      the neural cell adhesion molecule, PSA-NCAM, and the glycoproteins, F3 and
      tenascin-C. 6. The expression of PSA-NCAM and tenascin-C does not show striking
      differences in terms of age, sex or physiological condition but that of F3 varies
      considerably with neurohypophysial stimulation. 7. We postulate that such
      molecular features allow magnocellular neurons and their glia to undergo neuronal
      glial and synaptic plasticity throughout life, provided the proper stimulus
      intervenes. 8. Thus, in the hypothalamic nuclei, centrally released oxytocin
      acting in synergy with steroids can induce such plasticity, while adrenaline,
      acting through beta-adrenergic mechanisms, does so in the neurohypophysis.

PMID- 9535295
TI  - Current therapy and new perspectives in the treatment of medulloblastoma.
AB  - Medulloblastoma, a malignant tumor arising from the medullary velum, is the most
      common malignant brain tumor of childhood. Local extension into the cerebellar
      hemisphere, infiltration of the floor of the fourth ventricle, and seeding into
      the subarachnoid space are common. Early diagnosis and improved treatment
      consisting of surgery followed by radiation and chemotherapy for selected high
      risk patients has contributed to a dramatic change in survival. This article
      reviews current treatment strategies and describes new therapies that have the
      potential to improve the outlook of children with medulloblastoma.

PMID- 9535296
TI  - Palmitoyl-protein thioesterase deficiency in a novel granular variant of LINCL.
AB  - Typically, late infantile neuronal ceroid-lipofuscinosis (LINCL) patients present
      between the ages of 2 and 4 years with progressive dementia, blindness, seizures,
      and motor dysfunction. Curvilinear profiles are seen on electron microscopic
      examination of tissues derived from those patients. Data were collected on 122
      LINCL cases, representing 81 independent families, diagnosed on the basis of age
      of onset, clinical symptomatology, and pathologic findings. Careful analysis of
      our data has revealed that 20% of these cases (24 of 122) show either an atypical
      clinical course or atypical pathologic findings and may represent variants of
      LINCL. Recent progress in the biochemistry and molecular genetics of NCL has led
      us to reevaluate these atypical cases. Five atypical LINCL cases (representing
      three independent families) manifested granular inclusions when examined by
      electron microscopy, a finding normally associated with the infantile form of
      NCL. In addition, these five cases did not show elevated subunit c levels in
      urine (typically seen in LINCL). In these five cases, palmitoyl-protein
      thioesterase activity was found to be deficient (less than 10% normal activity),
      suggesting that these cases represent INCL, presenting at a later age of onset.
      These findings suggest that palmitoyl-protein thioesterase deficiency is not
      restricted to infantile onset cases, and they raise the possibility that milder
      forms of INCL may result from less deleterious mutations.

PMID- 9535297
TI  - Use of botulinum toxin injection in 17 children with spastic cerebral palsy.
AB  - The use of botulinum toxin was studied in 17 children with spastic cerebral palsy
      to determine its efficacy and tolerability. Eleven ambulatory and 6 nonambulatory
      patients were included. All children were undergoing a physiotherapy program with
      monitoring of their baseline states for 3 months before botulinum toxin
      injection. The effect was evident within 72 hours. The peak effect was noticed by
      1 to 2 weeks in the majority; the effect lasted for 3 to 10 months. All children
      experienced decreased spasticity scores. Their functional status improved, with
      three nonambulatory children becoming ambulatory with assistance and five
      children with assisted ambulation becoming more independently ambulatory.
      Measurement of joint motion showed improvement in the range of motion as compared
      with baseline. Video analysis of the functional state in the nonambulatory or
      gait in the ambulatory children revealed improvement in all. The functional
      status of rising from the sitting position or standing demonstrated improvement.
      None of the children had any untoward side effects except mild transient pain at
      the injection site. This study demonstrated botulinum toxin is useful as an
      adjunctive therapy in ameliorating spasticity in children with cerebral palsy,
      especially in the younger ones.

PMID- 9535298
TI  - Changes in cerebral blood flow velocities during childhood absence seizures.
AB  - A simultaneous recording of mean flow velocity in the right middle cerebral
      artery by transcranial Doppler ultrasonography and electroencephalographic
      activity was performed in 5 children with multiple daily typical absence
      seizures. Twenty-eight absence episodes were recorded. Mean flow velocity
      increased gradually a few seconds before the clinical and electroencephalographic
      manifestations of each seizure and reached the maximum values (range of increase:
      25.5-42.8% with respect to baseline) within 2-3 seconds from their onset. This
      increase was then followed by a fast reduction in flow velocity, with the lowest
      levels (range of decrease: 30.8-44.0% with respect to baseline) recorded within 4
      6 seconds from the end of each absence seizure. These findings suggest that
      changes in cerebral blood flow and activity are quite complex during absence
      seizures and that they do not fully correlate with clinical and
      electroencephalographic manifestations.

PMID- 9535299
TI  - Relaxation therapy in Tourette syndrome: a pilot study.
AB  - To evaluate the feasibility and efficacy of behavioral relaxation therapy as
      treatment for Tourette syndrome, 23 patients were recruited from a university
      based pediatric Tourette syndrome referral clinic. Individuals were randomized
      and stratified according to initial tic severity and the presence of attention
      deficit hyperactivity disorder into either relaxation therapy or a minimal
      therapy (control) group. Sixteen patients, mean age 11.8 years (S.D. 2.8 years),
      completed the 3-month study, which included weekly, hour-long, individual
      training sessions for 6 weeks. Individuals (n = 7) in the relaxation therapy
      group demonstrated a significantly increased ability to relax, compared with the
      minimal therapy (awareness and quiet time training) group. At 6 weeks, tic
      findings, based on five established tic severity scales, revealed greater
      improvement in the relaxation treatment group, but values failed to reach
      statistical significance. No difference between therapy groups was apparent at
      the 3-month evaluation. The acquired ability to relax did not significantly
      affect behavioral measures on the Child Behavioral Checklist. On the basis of
      this pilot study, relaxation therapy appears to have a limited role in the
      treatment of tics in Tourette syndrome.

PMID- 9535300
TI  - Life expectancy of children with cerebral palsy.
AB  - Risk factors for mortality of young children with cerebral palsy were studied
      using a sample of 12,709 children aged 0.5-3.5 years with cerebral palsy who had
      received services from the State of California between 1980 and 1995. The most
      powerful prognostic factors for survival were simple functional items: mobility
      and feeding skills. Once these were known, factors such as severity of mental
      retardation and presence of quadriplegia contributed relatively little. Children
      with fair motor and eating skills had good survival prospects, with 90% or more
      reaching adulthood, but those without such skills had much poorer prospects.
      Among children who were unable to lift their heads, median survival time was 7
      additional years for those who were tube fed (n = 557) and 14 years for those fed
      entirely by others (n = 997). Although a child's approximate survival chances can
      be assessed from such functional classifications, we indicate the manner in which
      additional information on the child's condition can be used to obtain more
      accurate survival data.

PMID- 9535301
TI  - Effects of an educational program on parents with febrile convulsive children.
AB  - The purpose of this study was to characterize the effects of an educational
      program on knowledge, attitude, concern, and first-aid measures among parents
      with febrile convulsive children. All parents completed a pretest questionnaire 3
      weeks before the meeting. The parents were assigned randomly into experimental (n
      = 65) and control (n = 64) groups on the day they attended the program. The
      control group completed the identical questionnaire (posttest) before the
      program, whereas the experimental group completed the same posttest after the
      program. In pretest, most parents considered electroencephalogram or computed
      tomography necessary in evaluating their children, suggested that immunization be
      postponed, and rated the risk of subsequent epilepsy as high for their children.
      Most of them favored frequent body temperature measurement, were very anxious
      about further febrile convulsion episodes during the night, and were fever
      phobic. After education, although only a slight change in fever anxiety was
      found, the experimental group showed significant improvement in knowledge,
      attitude, concerns, and anticipatory practice of febrile convulsion compared with
      the control group. In conclusion the parents' poor knowledge, negative attitudes,
      anxiety, and inadequate first-aid measures toward febrile convulsion can be
      effectively improved by an educational intervention program.

PMID- 9535302
TI  - Mollaret's recurrent aseptic meningitis and cerebral epidermoid cyst.
AB  - A patient who initially presented with clinical and laboratory signs of bacterial
      meningitis developed four more similar episodes within a 6-month period. Immune
      system studies were unremarkable. A tentative diagnosis of Mollaret's meningitis
      was established after the third episode. Cranial computed tomography performed
      during the acute phase of the initial episode was normal, but, after the fourth
      scan, when the patient was asymptomatic, magnetic resonance imaging revealed a
      cyst in the anterior aspect of the medulla. Partial excision allowed for
      pathologic analysis, which established the diagnosis of epidermoid cyst. The
      differential diagnosis of recurrent aseptic meningitis should include Mollaret's
      meningitis and dermoid-epidermoid cysts. Neuroimaging studies, preferably
      magnetic resonance imaging, should be performed at a time when patients are
      asymptomatic.

PMID- 9535303
TI  - Mycoplasma pneumoniae meningoencephalitis and cerebellitis with antiganglioside
      antibodies.
AB  - A male patient with acute meningoencephalitis and cerebellitis associated with
      Mycoplasma pneumoniae infection is described. T2-weighted MRI demonstrated a high
      intensity lesion involving the deep white matter of the right cerebellar
      hemisphere, which was not enhanced on injection of gadolinium. Brain perfusion
      scintigraphy revealed hypoperfusion in the bilateral cerebellar hemisphere.
      Polymerase chain reaction analysis using M. pneumoniae-specific primers failed to
      reveal the existence of the M. pneumoniae genome in cerebrospinal fluid.
      Conversely, serum antibodies to gangliosides (GM1, GM2, and GT1b) were detected,
      suggesting a mycoplasma-related neurologic disorder mediated by an immunologic
      mechanism. These findings support the hypothesis that vasculopathy and
      demyelination caused by an immunologic mechanism play an important role in the
      pathogeneses of neurologic disorders associated with M. pneumoniae infection.

PMID- 9535304
TI  - Successful use of intravenous immunoglobulins in Landau-Kleffner syndrome.
AB  - A detailed history of a boy with Landau-Kleffner syndrome is presented,
      demonstrating a close relationship between language functioning and paroxysmal
      electroencephalogram activity. During a 3-year 6-month follow-up period, three
      abrupt deteriorations of all language functions occurred: the child became
      totally noninteractive with his environment within 1 week's time. Two of these
      deteriorations were reversed with steroid treatment, with an identical recovery
      phase. Intravenous immunoglobulins had a very dramatic and comparable effect in
      the third relapse; both language functions and electroencephalogram abnormalities
      were influenced significantly by the intravenous immunoglobulin treatment.

PMID- 9535305
TI  - Hydrocephalus as a possible early symptom in a child with a spinal cord tumor.
AB  - Spinal cord tumors are relatively uncommon in children. These tumors have been
      associated with increased intracranial pressure in both children and adults. An
      infant presented initially with hydrocephalus and subsequently developed symptoms
      consistent with spinal cord abnormalities. Various proposed etiologies for
      increased intracranial pressure in spinal cord tumors are presented. Spinal cord
      tumors should be considered in the presence of childhood hydrocephalus and
      increased intracranial pressure without a clearly defined etiology.

PMID- 9535306
TI  - Stroke and fibromuscular dysplasia: confirmation by renal magnetic resonance
      angiography.
AB  - Childhood stroke is uncommon and may require extensive evaluation to elucidate an
      underlying cause. A 9-year-old boy had clinical and magnetic resonance imaging
      (MRI) features of an ischemic event in the left middle cerebral artery territory.
      Magnetic resonance angiography (MRA) revealed beading of the left middle cerebral
      artery, consistent with irregular blood flow secondary to turbulence or luminal
      narrowing. Conventional angiography of the cerebral vessels confirmed the
      findings of cerebral MRA and raised further the suspicion of fibromuscular
      dysplasia (FMD). MRA of the renal vessels was subsequently performed, revealing
      beading of the left renal artery and confirming the diagnosis of FMD. MRA, a
      rapid and less invasive technique associated with far less morbidity and
      mortality as compared with conventional angiography, may prove to be as sensitive
      as conventional angiography in detecting the changes of FMD. MRA of the renal
      arteries should be performed with initial cranial MRI and MRA in children who
      present with cerebral infarction of possible vascular origin. This may obviate
      the need to perform further investigations and may make early diagnosis possible
      at the first MRI scan and under a single general anesthetic.

PMID- 9535307
TI  - Proton magnetic resonance spectroscopy of linear nevus sebaceus syndrome.
AB  - Cerebral metabolites of a patient with linear nevus sebaceus syndrome and
      hemimegalencephaly were determined at 18 and 30 months of age by localized proton
      magnetic resonance spectroscopy. Clinically, the patient suffered from
      hemiparesis and epileptic seizures. At 18 months of age, spectroscopy of the
      enlarged hemisphere revealed decreased N-acetylaspartate mainly in parietal white
      matter relative to the unaffected hemisphere. One year later, white matter
      studies indicated both reduced N-acetylaspartate and elevated myoinositol. In
      insular gray matter the previously normal concentrations of creatine, choline
      containing compounds, myoinositol, and glutamine were increased. The findings are
      consistent with mild neuroaxonal loss or damage (white matter) and glial
      proliferation (cortical gray and white matter) of the affected hemisphere. The
      metabolic disturbances indicate disease progression but are less pronounced than
      in older patients with hemimegalencephaly.

PMID- 9535308
TI  - High-dose intravenous immunoglobulin in transient neonatal myasthenia gravis.
AB  - A preterm newborn had transient neonatal myasthenia gravis and was mechanically
      ventilated for 9 days. In addition to the usual supportive care, she was treated
      with neostigmine and underwent two exchange transfusions. High-dose intravenous
      immunoglobulin therapy (2 gm/kg) was used for the first time in transient
      neonatal myasthenia gravis to the best of our knowledge. The clinical and
      laboratory responses are presented.

PMID- 9535309
TI  - Efficacy and technical complications of long-term continuous intraspinal
      infusions of opioid and/or bupivacaine in refractory nonmalignant pain: a
      comparison between the epidural and the intrathecal approach with externalized or
      implanted catheters and infusion pumps.
AB  - OBJECTIVE: To compare efficacies, failure rates, and technical complication rates
      of intraspinal treatments in patients with "refractory" nonmalignant pain
      conditions in relation to the approach (epidural/intrathecal), the drug
      (opioid/opioid-bupivacaine or bupivacaine), and the type of system used
      (externalized/internalized). In these comparisons, recent data from a companion
      paper (Nitescu et al., Clin J Pain 1998;14:17-28) were used as a reference to be
      compared with data from a literature review of different intraspinal treatment
      modalities in nonmalignant pain. DESIGN: Prospective, cohort, nonrandomized,
      consecutive trial. SETTING: Tertiary care center, institutional practice,
      hospitalized, and ambulatory care. PATIENTS: Five groups according to treatment
      modality: (a) externalized, long-term intrathecal nylon catheters, connected to
      external, electronic infusion pumps (companion paper), n = 90; (b) internalized,
      long-term intrathecal catheters (Silastic) connected to implanted SynchroMed
      pumps, n = 330 (literature review); (c) externalized, "short-term" epidural
      catheters for "temporary" infusions, n = 565 (literature review); (d)
      externalized, long-term epidural catheters, n = 50 (literature review); (e)
      internalized, long-term epidural catheters, n = 111, connected to implanted
      systems: Port-A-Cath injection ports, n = 58; Infusaid pumps, n = 46; and
      SynchroMed pumps, n = 7 (literature review). INTERVENTIONS: In reviewing the
      literature, we found 21 studies that reported on the intraspinal (epidural or
      intrathecal) administration of opioids with or without local anesthetics (usually
      bupivacaine). These studies were analyzed with respect to the rates of the
      variables satisfactory pain relief (efficacy), failures, and technical
      complications. A rate is the number of observations of a variable divided by the
      number of patients or the number of catheters or infusion systems, as logically
      indicated (e.g., the numbers of complications, such as epidural abscess and
      meningitis, were related to the number of patients and those of catheter
      occlusion or leakage to the number of the catheters). The variables were
      expressed as the means of the rates of a variable from studies belonging to
      various treatment modalities: approach (epidural vs. intrathecal), duration
      (short vs. long term), drugs administered intraspinally (opioid vs. opioid and/or
      local anesthetic), and type of infusion system (externalized vs. internalized).
      Further, the sums of all observations of one variable in different studies with
      various treatment modalities were related to the corresponding sums of the
      patients (alternatively, catheters or implanted devices). The proportions of
      these sums were tested for significance in relation to treatment modality. MAIN
      OUTCOME MEASURES: Comparative rates of successful intraspinal treatment and its
      failures and complications. RESULTS: (a) The intrathecal approach, compared with
      the epidural approach, was associated with higher rates of satisfactory pain
      relief for both externalized (86/90, 95% vs. 17/40, 42.5%, p < .0001) and
      internalized (295/336, 89% vs. 33/56, 59%, p < .0001) catheters; higher rates of
      treatment failures with externalized epidural catheters than with internalized
      intrathecal catheters (24/47, 51%, vs. 36/338, 11%, p < .0001); lower rates of
      treatment failures with internalized intrathecal catheters than with internalized
      epidural catheters (36/338, 11% vs. 29/76, 38%, p < .0001); higher rates of
      system replacement with internalized epidural catheters than with internalized
      intrathecal catheters (23/32, 72% vs. 6/49, 12%, p < .0001; higher rates of
      system removal with internalized epidural catheters than with internalized
      intrathecal catheters (22/49, 45% vs. 5/49, 10%, p < .001); higher rates of
      catheter-related complications with epidural than with intrathecal catheters
      (dislodgement 13/126, approximately 10% vs. 6/150, 4%, p < .05; leakage 5/51,
      approximately 10% vs. 1/116, 0.9%, p < .05; obstruction 2

PMID- 9535310
TI  - Continuous infusion of opioid and bupivacaine by externalized intrathecal
      catheters in long-term treatment of "refractory" nonmalignant pain.
AB  - OBJECTIVE: To explore the possibility of obtaining pain relief by continuous
      intrathecal infusion of bupivacaine and opioid in patients with intractable
      nonmalignant pain. DESIGN: Prospective, cohort, nonrandomized, consecutive trial.
      SETTING: Tertiary care center, institutional practice, hospitalized, and
      ambulatory care. PATIENTS: A total of 90 patients, 40 men and 50 women, 20 to 96
      years old (median, 70 years), with various nonmalignant "refractory" pain
      conditions lasting for 0.3 to 50 years (median, 3 years) with nociceptive (n =
      9), neurogenic/neuropathic (n = 17), and mixed pain (n = 64) were consecutively
      included in the study when (a) the pain dominated their lives totally, (b) other
      methods failed to provide acceptable pain relief, and (c) unacceptable side
      effects from opioids had occurred. Moribund patients and those with overt
      psychoses at the time of the assessment were excluded from the study.
      INTERVENTIONS: (a) Insertion of externalized, tunnelled intrathecal catheters
      (101 in 90 patients). (b) Intrathecal infusion of opioid (morphine 0.5 mg/ml, or
      buprenorphine 0.015 mg/ml, and/or bupivacaine 4.75-5.0 mg/ml) from external
      electronic pumps was started in the operating room at a basic rate of 0.2
      ml/hour, with optional bolus doses (0.1 ml 1-4 times/hour) by patient-controlled
      analgesia (PCA). Thereafter, the daily volumes were tailored to give the patients
      satisfactory to excellent (60-100%) pain relief, with acceptable side effects
      from the infused drugs, by increase or decrease of the basic rates and/or of the
      bolus doses, and their timing. (c) Supervision of the patients for 24 hours after
      catheterization in the postoperative ward. (d) Daily phone contact with the
      patients, their families, or the nurses in charge. (e) The patients had ad
      libitum access to nonopioid analgesics/sedatives and to opioids administered by
      various routes, until they obtained satisfactory pain and anxiolytic relief. MAIN
      OUTCOME MEASURES: (a) Pain intensity (visual analog scores 0-10) and pain relief
      (0-100%). (b) Daily dosages (opioid administered by intrathecal and other routes,
      and intrathecal bupivacaine). (c) Scores (0-5) of nonopioid analgesics, gait and
      ambulation, duration of nocturnal sleep, and (d) rates of adverse effects.
      RESULTS: During the intrathecal period [range, 3-1,706 days; median, 60 days;
      totaling 14,686 days, 7,460 (50% of which were spent at home)], 86 patients
      (approximately 95%) obtained acceptable (60-100%) pain relief. The nocturnal
      sleep duration increased from <4 to 7 hours (median values), nonopioid analgesic
      and sedative daily consumption became approximately two times lower, whereas the
      gait ability and ambulation patterns remained practically unchanged. Five
      patients still had ongoing treatment after durations of 30 to 1,707 (median, 206)
      days at the close of the study. In the remaining 85 patients, the intrathecal
      treatment was terminated because of patients' death (n = 23), replacement of the
      intrathecal treatment by dorsal column stimulation (n = 1), pain resolution (n =
      32), refusal to continue the intrathecal treatment (n = 19), lack of cooperation
      due to delirium or to manipulation of the pump (n = 8), and loss of efficacy of
      the intrathecal treatment (n = 2). Thus, in the long run, the intrathecal
      treatment failed in 29 of the 85 patients with terminated treatment (34%). The
      principal side-effects and complications, except those attributed to the dural
      puncture, the equipment, and the long-term catheterization of the subarachnoid
      space, which are presented separately, were severe bradypnea (n = 1), transient
      paresthesiae (n = 26), short-lasting pareses (n = 16), temporary urine retention
      (n = 34), episodic orthostatic arterial hypotension (n = 11), and attempted
      suicide (n = 5, 3 of which were successful). No neurologic sequelae or death
      could be attributed to the intrathecal procedure. (ABSTRACT TRUNCATED)

PMID- 9535311
TI  - Evaluation of the Faces Pain Scale for use with the elderly.
AB  - OBJECTIVE: The specific objective for this research was to determine initial
      psychometric properties of the Faces Pain Scale (FPS) as a measure of pain
      intensity for use with the elderly. DESIGN: The study was descriptive
      correlational in nature, with nonrandom sampling. A total sample of 168 community
      subjects (30-121, depending on task completed), aged 65 or older, participated in
      the research protocol. To determine the validity, reliability, and scaling
      properties of the FPS, rating and ranking procedures, placement tasks, and test
      retest methods were used. RESULTS: Response to six Likert-type items indicated
      that subjects agreed that the FPS represents pain: however, it is clear that the
      perception of the meaning of the faces can be influenced by the context in which
      they are presented. Rank ordering tasks for the individual faces demonstrated
      near-perfect agreement between the actual expected ranking and the ranking
      produced by the subjects (Kendall's W = .97, p = .00). When subjects placed
      individual faces along a 1-m-long red wedge indicating the amount of pain
      represented by each face, statistically significant separation of the faces in
      the anticipated equal interval position was demonstrated by the lack of overlap
      of the 95% confidence intervals when all faces were viewed and positioned
      simultaneously. However, when subjects placed faces independent of others, the
      expected placement fell outside the 95% confidence limit for three of the five
      faces placed. In addition, the actual intervals between the five faces placed by
      subjects demonstrated substantial variances from the 167 mm expected in several
      instances. Rating a vividly remembered painful experience about the degree of
      pain perceived using the FPS initially and again 2 weeks later, the FPS
      demonstrated strong reproducibility over time with a Spearman rho correlation
      coefficient of .94 (p = .01). CONCLUSION: These results provide preliminary
      support for the construct validity, strong ordinal properties, and strong test
      retest reliability of the FPS with a sample of elderly individuals. The equality
      of intervals in the FPS has not been fully supported in the older adult, but
      given the complexity of the task used, the results should not be considered to be
      refuted. Further evaluation of the FPS with experimental and clinical pain
      conditions and comparison with other standard pain assessment instruments in the
      elderly population are warranted.

PMID- 9535312
TI  - A simultaneous comparison of three neonatal pain scales during common NICU
      procedures.
AB  - OBJECTIVE: This study evaluated neonatal pain scales during procedures commonly
      performed in a neonatal intensive care unit. DESIGN: Evaluated were the Neonatal
      Infant Pain Scale (NIPS), the Comfort scale, and a new scale known as the Scale
      for Use in Newborns (SUN). Four procedures were scored: intubation, intravenous
      catheter insertion, endotracheal tube suctioning, and diaper changes. Scoring was
      done before, during, and after each procedure. Thirty-three patients were tested
      during 68 procedures with 1,428 scale scores. RESULTS: All scales demonstrated
      significant changes. In before-versus-during for each procedure, the increase in
      pain scale score was significant for the NIPS, Comfort scale, and SUN. All three
      scales also demonstrated a return to baseline (before-vs.-after) for the four
      procedures, except for the Comfort scale, which remained elevated (p < .05)
      following diaper change. The NIPS had a significantly larger coefficient of
      variation (CV, 188% +/- 99%), whereas the Comfort scale and SUN had small CVs
      (27% +/- 5% and 33% +/- 8%, respectively). In evaluating potential confounding
      influences, it was found that infants > 2.5 kg on sedative or analgesic
      medications appeared to have procedure-related accentuation and sustained
      elevation in scale scores, whereas swaddling seemed to provide little added
      benefit. CONCLUSIONS: The pain scale scores identify changes in an infant's
      behavior/physiologic state. It is unclear whether these changes are totally "pain
      specific." In comparing the three scales, the SUN overall was a preferable tool
      because of its ease of use, scale symmetry, and scoring consistency.

PMID- 9535313
TI  - IASP diagnostic criteria for complex regional pain syndrome: a preliminary
      empirical validation study. International Association for the Study of Pain.
AB  - OBJECTIVE: To assess the ability of the International Association for the Study
      of Pain Complex Regional Pain Syndrome (CRPS) diagnostic criteria and associated
      features to discriminate between CRPS patients and patients with painful diabetic
      neuropathy. DESIGN: Prospective assessment of signs and symptoms in a series of
      CRPS and diabetic neuropathy patients. SETTING: University of Washington
      Multidisciplinary Pain Center. PATIENTS: A consecutive series of 18 CRPS patients
      and 30 diabetic neuropathy patients. INTERVENTIONS: Patients completed a 10-item
      patient history questionnaire assessing symptoms of CRPS prior to medical
      evaluation. The evaluating physician completed a 10-item patient examination
      questionnaire assessing objective signs of CRPS. OUTCOME MEASURES: The analyses
      conducted were designed to test the ability of CRPS signs and symptoms and
      associated features to discriminate between CRPS patients and diabetic neuropathy
      patients. RESULTS: Data analysis suggested that CRPS decision rules may lead to
      overdiagnosis of the disorder. Diagnosis based on self-reported symptoms can be
      diagnostically useful in some circumstances. The addition of trophic tissue
      changes, range of motion changes, and "burning" quality of pain did not improve
      diagnostic accuracy, but the addition of motor neglect signs did. Test of a CRPS
      scoring system resulted in improved accuracy relative to current criteria and
      decision rules. CONCLUSIONS: Poorly understood disorders lacking prototypical
      signs/symptoms and diagnostic laboratory testing must rely on the development of
      reliable diagnostic guidelines. The results of this study should assist in the
      further refinement of the CRPS diagnostic criteria.

PMID- 9535314
TI  - Relations of employment status to emotional distress among chronic pain patients:
      a path analysis.
AB  - OBJECTIVE: This cross-sectional study evaluated the extent to which relations
      between employment status and emotional distress are mediated by pain-related and
      psychosocial measures among employed and unemployed persons with chronic pain.
      DESIGN: A total of 40 unemployed and 43 employed persons reporting chronic pain
      were recruited from pain services at a tertiary-care hospital and community-based
      organizations. Volunteers completed self-report measures of pain severity,
      subjective financial stress, time structure, emotional distress, and background
      data. RESULTS: A path analysis indicated that pain severity had direct
      associations with both emotional distress and employment status. In addition,
      employment status was only indirectly related to emotional distress; this
      relation was mediated by levels of reported financial strain and structured
      purposeful time use. CONCLUSIONS: Findings suggest that pain severity and the
      quality of specific experiences related to being employed or unemployed as
      opposed to employment status per se correspond directly to levels of emotional
      distress reported by some persons with chronic pain.

PMID- 9535315
TI  - Effect of carbamazepine on pain scores of unipolar depressed patients with
      chronic pain: a trial of off-on-off-on design.
AB  - OBJECTIVE: The purpose of this study was to evaluate the effect of carbamazepine
      on chronic pain in patients with major depression. DESIGN: Off-on-off-on
      carbamazepine treatment design. SETTING: Department of Anesthesiology, Hirosaki
      University Hospital, Japan. PATIENTS: Fifteen patients with a diagnosis of major
      depression and chronic pain. INTERVENTION: Depressed patients maintained on
      antidepressants that had failed to help depression or pain were initially placed
      on 450 mg carbamazepine at 150 mg three times per day. Carbamazepine was then
      increased until the patients experienced satisfactory relief of pain. This dose
      was then maintained for 3 weeks. Afterward, the medication was stopped, and a
      lactose placebo was administered orally three times per day for 3 weeks.
      Thereafter, carbamazepine was given for 3 additional weeks at the dose that
      previously produced satisfactory pain relief. OUTCOME MEASURE: Pain scores were
      assessed four times during the course of the study: before and after the first
      and the second treatments with carbamazepine, using a visual analog scale in
      which 0 represents no pain and 10 unbearable pain. The Hamilton Depression scale
      was used to judge improvement in the symptoms of depression. RESULTS:
      Carbamazepine produced a statistically significant reduction in the pain scores,
      from 8.2 +/- 2.3 to 4.0 +/- 1.1 after the first treatment. The pain score
      significantly increased to 8.0 +/- 1.0 after stopping carbamazepine, but it
      decreased significantly to 4.1 +/- 1.8 after the second treatment. The Hamilton
      scores significantly decreased from 27.4 +/- 7.2 to 20.2 +/- 6.1 after the
      carbamazepine treatment. CONCLUSIONS: These results may indicate that
      carbamazepine has both an antidepressive and an analgesic action in depressed
      patients. Thus, carbamazepine may offer an acceptable therapeutic option in
      depressed patients with chronic pain that is unresponsive to antidepressants.
      Alternatively, these results may indicate that carbamazepine appears to help
      depression in this group of pain patients because of its analgesic effect (i.e.,
      helps depression as a result of helping pain or vice versa).

PMID- 9535316
TI  - Long-term transcutaneous electrical nerve stimulation (TENS) use: impact on
      medication utilization and physical therapy costs.
AB  - OBJECTIVE: A study was conducted to assess a variety of treatment outcomes in
      long-term users of transcutaneous electrical nerve stimulation (TENS) who suffer
      from chronic pain. Key components of the study examined the effects of long-term
      TENS therapy on pain-related medications and physical/occupational therapy
      (PT/OT) use. DESIGN: From a population of 2,(X)3 chronic pain patients (CPPs) who
      acquired a TENS device (Epix XL, Empi, Inc., St. Paul, MN, U.S.A.) for pain
      management, a randomly selected sample of 376 patients who used TENS were
      interviewed by telephone by an independent research firm. The survey assessed a
      variety of outcome variables including changes in medication use, number of pain
      related medications, and use of PT/OT prior to TENS and after a minimum 6 months
      of TENS treatment. The data were subjected to a paired t test analysis. A cost
      simulation model was then applied to the medication and PT/OT data. RESULTS: The
      mean duration of pain, for which TENS was prescribed, was 40 +/- 60 months. As
      compared with the period prior to TENS use, this long-term TENS user group
      reported a statistically significant reduction in the following types of pain
      medications: opiate analgesics, tranquilizers, muscle relaxants, nonsteroidal
      anti-inflammatory drugs (NSAIDs), and steroids. PT/OT use was also significantly
      reduced. Cost simulations of pain medications and PT/OT are presented.
      CONCLUSIONS: Long-term use of TENS is associated with a significant reduction in
      the utilization of pain medication and PT/OT. In this study population, cost
      simulations of medication and PT/OT indicate that with long-term TENS use, costs
      can be reduced up to 55% for medications and up to 69% for PT/OT. The potential
      for TENS associated improvement, combined with reduced medication-related
      complications and costs, are important points that clinicians should consider
      when constructing a treatment plan for chronic pain patients. Finally, cost
      simulation techniques provide a useful tool for assessing outcomes in pain
      treatment and research.

PMID- 9535317
TI  - Myofascial pain syndrome and fibromyalgia: a critical assessment and alternate
      view.

PMID- 9535318
TI  - Effect of barbiturate on central pain: difference between intravenous
      administration and oral administration.
AB  - OBJECTIVE: To examine whether the oral administration of barbiturates is of
      clinical use in a patient with central pain. SETTING: Pain Clinic, Osaka
      University Medical Hospital, Osaka, Japan. PATIENT: A patient with central pain
      after loss of his left upper extremity. INTERVENTIONS: A 50-mg dose of
      intravenous amobarbital, which produced a plasma concentration of 2.5-4.0
      microg/ml, was effective in reducing the central pain. Subsequently, doses of 300
      400 mg/day were administered orally; these succeeded in achieving similar plasma
      concentration levels. RESULTS AND CONCLUSIONS: Oral administration of barbiturate
      did not alleviate central pain, even when the plasma concentration was the same
      as the effective level in intravenous use. Pharmacokinetic and pharmacodynamic
      factors more complex than simple plasma concentrations may be involved in
      producing the difference in the effects.

PMID- 9535319
TI  - Opioids and chronic pain.

PMID- 9535320
TI  - Opiate abuse or undertreatment?

PMID- 9535322
TI  - Influence of predeprivation diet nutrient density and sodium chloride content on
      nutrient losses and repletion in lambs.
AB  - Six crossbred lambs (32+/-2 kg) in a 6 x 6 Latin square design were used to
      determine the effects of predeprivation diet nutrient density and NaCl content on
      nutrient losses during periods of feed and water deprivation and nutrient
      repletion. Treatments consisted of two predeprivation dietary nutrient densities
      (low [LOW] and moderate [MOD]) and three NaCI intakes (0, 2, or 4 g/d) in a 2 x 3
      factorial arrangement. During the 4-d predeprivation phase, lambs fed the M0D
      diet had greater (P < .05) K retention and lower (P < .01) Na retention than
      lambs fed the LOW diet. Retention of Na increased linearly (P< .01), whereas
      retention of K decreased linearly (P < .O01) with increasing NaCl intakes. During
      the 3-d deprivation phase, lambs fed the MOD diet had lower (P < .01) Na losses
      than lambs fed the LOW diet. Losses of Na increased linearly (P < .01), whereas
      losses of K decreased linearly (P < .05) with increasing NaCl intakes. During the
      predeprivation and deprivation phases, cumulative losses of K were greater (P <
      .05) and cumulative losses of Na were lower (P < .05) in lambs fed the LOW diet
      than in lambs fed the MOD diet. Cumulative losses of K increased linearly (P <
      .05) as predeprivation NaCl intake increased. Predeprivation NaCl intakes did not
      affect (P > .10) total retention of water, Na, or K for the overall 14-d sampling
      period. Predeprivation salt intakes affected Na and K losses during a simulated
      marketing-transport period. However, after 7 d on the realimentation diet,
      predeprivation diet nutrient density and NaCl intake did not affect the balance
      of these nutrients.

PMID- 9535323
TI  - Effects of corn processing, dietary roughage level, and timing of roughage
      inclusion on performance of feedlot steers.
AB  - In Trial 1, 108 crossbred steer calves (initial BW 295 kg) were allotted to 12
      pens and used in a 186-d feedlot trial to determine the effects of increasing or
      decreasing roughage level on feedlot performance and carcass characteristics.
      Four dietary treatments were investigated: 1) 85% concentrate diet fed for 186 d,
      2) 100% concentrate diet fed for 186 d, 3) 85% concentrate diet fed for 84 d
      followed by a 100% concentrate diet for the remaining 102 d, and 4) 100%
      concentrate diet for 84 d followed by an 85% concentrate diet for the remaining
      102 d. Corn silage was added as roughage. During the first 84 d, level of dietary
      concentrate did not affect (P > .10) ADG. Steers switched to the 85% concentrate
      diet for the last 102 d had higher (P < .05) DMI than those fed the 100%
      concentrate diet; they did not exhibit an increase in ADG. Finishing phase feed
      efficiency was highest (P < .05) for steers continually fed 100% concentrate,
      lowest (P < .05) for steers continually fed 85% concentrate, and intermediate for
      steers whose concentrate level was switched during the trial. Carcass
      characteristics were not affected (P > .10) by concentrate level regimen. In
      Trial 2, 108 crossbred steer calves (initial BW 319 kg) were allotted to 12 pens
      and used in a 158-d trial to determine whether feedlot performance could be
      enhanced by manipulating roughage level and grain processing. Factors
      investigated were staged increases in concentrate level (70 to 85 to 100%) vs
      staged decreases in concentrate level (100 to 85 to 70%) and whole vs rolled high
      moisture corn. Corn silage was added as roughage. Diet concentrate levels were
      changed on d 56 and 112. During the first 56 d, steers fed 70% concentrate diets
      grew 11% faster (P < .05) and consumed 19% more feed (P < .05) than those fed
      100% concentrate diets. Steers fed rolled corn gained 8% faster (P < .06) and
      were 7% more efficient (P < .06) than those fed whole corn. During the last
      period (d 113 to 158), ADG was not affected (P > .10) by concentrate level or
      corn processing. Although increasing roughage during the feeding period increased
      feed intake in these trials, steer performance was not enhanced. Processing high
      moisture corn did not affect feedlot performance.

PMID- 9535321
TI  - Adipose tissue partitioning of limit-fed beef cattle and beef cattle with ad
      libitum access to feed differing in adaptation to heat.
AB  - We compared fat distribution and lipoprotein lipase (LPL) activity in steers
      differing in adaptability to the subtropics. Steers were fed a grain diet (3.13
      Mcal ME/kg DM) at limited (150 kcal ME x kg[-.75] x d[-1]; .23 kg ADG) or ad
      libitum levels for 140 d, then slaughtered. Sixteen British- (8 Angus, 8
      Hereford; S), 16 Boran- (R), 16 Brahman- (B), and 16 Tuli- (T) cross steers from
      MARC III composite cows were used. Adipose tissue samples from perirenal,
      omental, and subcutaneous depots were analyzed for LPL activity. Carcass
      measurements including omental, external, and seam fat trim from 1/ 2 of the
      carcass were measured. Subcutaneous fat had greater (P < .05) LPL activity than
      fat from the other depots. Generally, there were no differences (P > .05) in fat
      distribution for steers fed at limited levels. Means for ADG, slaughter weights,
      carcass weights, yield grades, and carcass lipid weights for S and B fed for ad
      libitum intake were greater (P < .05) than those for T and R. Marbling was
      greatest (P < .05) for S and did not differ (P > .05) for the other breeds with
      ad libitum intake. Factor analysis of fat depots for animals with ad libitum
      intake indicated that Bos taurus cattle differing in adaptation to heat deposited
      fat differently; S deposited greater (P < .05) proportions of carcass fat and T
      deposited greater (P < .05) proportions of internal fat. It seems that
      accumulation of internal fat is detrimental for ADG for Bos taurus cattle.

PMID- 9535324
TI  - Nutrient utilization by sheep and performance and carcass characteristics of
      steers fed crab waste-straw silage.
AB  - Crab waste preserved with .2% NaOCl was mixed with wheat straw, liquid molasses,
      and water (32:32:16:20, wet basis) and ensiled for a minimum of 8 wk with
      microbial inoculant. A reduction in pH and water-soluble carbohydrates (WSC) and
      a higher concentration of lactic acid (4.9%, DM basis) were achieved. The
      trimethylamine (TMA) concentration in the silage was 11.2 mg N/100 g. In a
      digestion trial, 18 crossbred wethers (43 kg) were fed three diets: 1) basal, 2)
      a 50:50 mixture, DM basis, of basal and crab waste-straw silage, and 3) 100% crab
      waste-straw silage. Apparent digestibility of DM, OM, CP, energy, NDF, ADF,
      cellulose, and hemicellulose decreased linearly (P < .01) with increased levels
      of crab waste-straw silage. Nitrogen retention increased linearly (P < .05) with
      level of crab waste-straw silage. Apparent absorption was higher (P < .01) and
      retention was positive (P < .05) for Ca, Mg, Na, K, Cu, and Fe for sheep fed the
      highest level of crab waste-straw silage. In a 108-d trial, 30 yearling steers
      were fed diets in which crab waste-straw silage was included in the diet at 0,
      15, and 26%, DM basis. Average daily gain tended to be highest (linear effect, P
      < .15) and carcass weights were highest (linear effect, P < .05) for steers fed
      26% crab waste-straw silage. Average carcass quality grade was low Choice, and
      yield grade averaged 2.3, with no significant differences among treatments.
      Consumption of crab waste-straw silage did not adversely affect the taste of the
      meat. Results indicate that feeding crab waste-straw silage did not adversely
      affect nutrient utilization or performance of ruminants.

PMID- 9535325
TI  - Mapping quantitative trait loci for carcass and meat quality traits in a wild
      boar x Large White intercross.
AB  - An intercross between wild boar and a domestic Large White pig population was
      used to map quantitative trait loci (QTL) for body proportions, weight of
      internal organs, carcass composition, and meat quality. The results concerning
      growth traits and fat deposition traits have been reported elsewhere. In the
      present study, all 200 F2 animals, their parents, and their grandparents were
      genotyped for 236 markers. The marker genotypes were used to calculate the
      additive and dominance coefficients at fixed positions in the genome of each F2
      animal, and the trait values were regressed onto these coefficients in intervals
      of 1 cM. In addition, the effect of proportion of wild boar alleles was tested
      for each chromosome. Significant QTL effects were found for percentage lean meat
      and percentage lean meat plus bone in various cuts, proportion of bone in
      relation to lean meat in ham, muscle area, and carcass length. The significant
      QTL were located on chromosomes 2, 3, 4, and 8. Each QTL explained 9 to 16% of
      the residual variance of the traits. Gene action for most QTL was largely
      additive. For meat quality traits, there were no QTL that reached the
      significance threshold. However, the average proportion of wild boar alleles
      across the genome had highly significant effects on reflectance and drip loss.
      The results show that there are several chromosome regions with a considerable
      effect on carcass traits in pigs.

PMID- 9535326
TI  - Heterosis and breed additive effects for Hereford, Tarentaise, and the reciprocal
      crosses for calf traits.
AB  - Records from 595 straightbred Hereford (HH), straightbred Tarentaise (TT), and
      reciprocal-cross (HT) females, randomly mated to HH, TT, or HT bulls, were
      analyzed for estimates of heterosis and breed additive effects for calf traits
      that included birth weight (BWT), calving difficulty (DIFF), prebreeding (PRE)
      and postbreeding (PST) weight, weaning weight (WWT), weaning condition score
      (WCS), weaning hip height (WHH), and preweaning average daily gain (ADG). The
      statistical model included year, age of dam, sex, regression on age at time of
      measurement, and regressions for the genetic effects of breed individual, breed
      maternal, breed grandmaternal, individual heterosis, and maternal heterosis.
      Breed effects were coded to reflect TT- HH differences. Age at the time of
      measurement, year, age of dam, and sex were significant for most traits.
      Individual breed effects were important (P < .05) for BWT, PRE, PST, WCS, and WHH
      but not for WWT, resulting in lower weights, less condition, and taller animals
      for TT. Maternal breed effects did not influence BWT, but they were important ( P
      < .05) for PRE, PST, WWT, WCS, WHH, and ADG. Grandmaternal effects were only
      important for BWT and ADG. Individual and maternal heterosis were important (P <
      .05) for most traits measured, resulting in increased calf size, weight, and body
      condition.

PMID- 9535327
TI  - Use of competing conceptions of risk in animal agriculture.
AB  - This study considers a theory of risk as a means of coping with risk and
      uncertainty that have become a growing reality for animal agriculture. Microbial
      contaminations of food, waste management, animal products in the human diet, and
      transmissible spongiform encephalopathies (TSE) incorporate different conceptions
      of risk and require different approaches to handling the uncertainty involved. A
      dichotomous schema is suggested to assist understanding risk that may be adapted
      to recognizing and handling risk. The polar aspects of the proposal are the
      probabilistic approach at one end and the contextual understanding at the other.
      Probabilist conceptions of risk presume that risk is determined by probability
      and consequence. Contextual conceptions presume that management, law, regulation,
      media, and public perceptions, as well as the severity of the consequence, will
      figure prominently in decision making in the face of uncertainty. Relative
      emphasis on probabilistic characteristics shapes distinct understandings of risk
      that can be plotted between the poles. We are proposing that these
      conceptualizations need not be issues only for debate but also for recognition of
      the probabilistic or contextual nature of the risk. Specific actions and policy
      may be constructed on the basis of the conceptualization. The bovine spongiform
      encephalopathy/new variant Creutzfeldt-Jakob disease complex is examined
      philosophically and methodologically as a contextual challenge to animal
      agriculture and associated industries. As such, the TSE serve as a case study of
      effective application of risk theory to risks in animal agriculture.

PMID- 9535328
TI  - Evaluation of sexual behavior of hair sheep rams in a tropical environment.
AB  - We evaluated sexual behavior of St. Croix White (SC; n = 5) and Barbados
      Blackbelly hair (BB; n = 4) rams under two environmental conditions in the
      tropics. Sexually naive rams were individually exposed for 15 min to a
      restrained, ovariectomized ewe, three times during a 3-wk period in June, in a
      pen with shade (SHADE; 33.1+/-.3 degrees C) or without shade (SUN; 38.3+/-.3
      degrees C). Rectal temperature (RT) of rams was measured before and after each
      test. Sexual behaviors were recorded by observers outside the pens. The number of
      mounts and ejaculations were similar (P > .10) between the SUN (12.1+/-2.8 and
      3.6 +/-.5, respectively) and SHADE (10.7+/-2.9 and 3.4+/-.4, respectively) tests.
      There was no breed x test pen interaction for any of the behaviors recorded (P >
      .10). The BB rams mounted the ewe more (P < .04) than did the SC rams (15.7+/-2.8
      vs 7.3+/-2.7 mounts, respectively). The overall level of activity (foreleg kicks,
      attempted mounts, mounts, and ejaculations) was similar (P > .10) between BB and
      SC rams (64.9 +/-8.5 vs 45.4+/-8.5 events, respectively). Rectal temperature
      before testing was similar (P > .10) in BB and SC rams (39.4+/-.1 vs 39.4+/-.1
      degrees C, respectively). The change in RT of rams was not different (P > .10)
      between SUN and SHADE tests (.6 +/-.1 vs .8+/-.1 degrees C), but BB rams had a
      greater (P < .02) change in RT than SC rams (.9+/-.1 vs .5+/-.1 degrees C,
      respectively). The change in RT was positively correlated with time to first
      service (r = .39, P < .01) and number of mounts (r = .52, P < .001) and
      negatively correlated with number of services (r = -.47, P < .0008). These
      results show that under tropical conditions, hair sheep rams exhibit a full
      repertoire of sexual behaviors. There does not seem to be a negative influence of
      elevated ambient temperature during testing on the level of sexual behavior of
      these rams.

PMID- 9535329
TI  - Early sexual experience fails to enhance sexual performance in male goats.
AB  - We studied the effects of early sexual experience on the adult sexual performance
      of male dairy goats. Seven postpubertal males were exposed to an estrous female
      on four occasions during their 1st yr of life. These males were housed with six
      additional males (controls) that received no early sexual experience. As
      yearlings, the 13 males were individually exposed to two estrous does for 30 min
      on three occasions at weekly intervals. Mounts with and without ejaculation were
      recorded. Sexually experienced and inexperienced males did not differ for either
      of these variables or a measure of mating efficiency (mounts per ejaculation).
      Mating efficiency improved for the experimental males during their four initial
      exposures to estrous females (P < .05). We conclude that male goats, in contrast
      to male sheep, are not likely to exhibit substandard sexual performance if denied
      heterosexual experience in their 1st yr.

PMID- 9535330
TI  - Growth performance of pigs subjected to multiple concurrent environmental
      stressors.
AB  - The effects of many single stressors have been reported, but how pigs perform
      when subjected to more than one or two stressors at a time, as is common in
      commercial swine production, has not. To study this, 256 Yorkshire x Hampshire or
      purebred Duroc pigs (34.7+/-.5 kg) were subjected to one of the eight treatment
      combinations (2 x 2 x 2 factorial) of ambient temperature (constant thermoneutral
      [24 degrees C] or high cycling temperature [28 to 34 degrees C]), stocking
      density (.56 or .25 m2/pig), and social group (static group or regrouped at the
      start of wk 1 and 3) during a 4-wk experiment. The temperature regimens were
      imposed in two adjacent mechanically ventilated rooms, and each temperature was
      imposed in each room across two trials. Four barrows and four gilts were assigned
      to each of the eight pens in the two rooms, and they always had free access to
      water and a corn-soybean meal-based diet. Treatments were imposed after a 7-d
      acclimation period at 24 degrees C and .56 m2/pig. Weight gain and feed intake
      were measured weekly. The main effects of each of the stressors for 4-wk ADG and
      ADFI were significant (P < .05). The stress of high temperature, high stocking
      density, and regrouping depressed 4-wk ADG by 12, 16 and 10% and ADFI by 7, 6,
      and 5%, respectively. Of the possible 60 stressor interactions for ADG, ADFI, and
      gain:feed (G:F), there were no significant three-way interactions and only six
      two-way interactions, suggesting that the effects of the individual stressors
      were additive. Accordingly, the growth rate of pigs subjected to the single
      stressor of high cycling temperature, restricted space allowance, or regrouping
      was depressed 10, 16, and 11%, respectively, and ADG of pigs subjected to all
      three stressors simultaneously was depressed by 31%. Stressor additivity was
      further corroborated by examining the effect of stressor order, or the number of
      stressors imposed simultaneously. As the number of stressors increased from 0 to
      3, ADG, ADFI, and G:F decreased linearly. These data suggest that multiple
      concurrent stressors affect growth performance of pigs in a predictable fashion
      (i.e., additively) and indicate that avoidance or removal of a given stressor is
      advantageous even when other uncontrollable stressors persist.

PMID- 9535331
TI  - Food flavor and nutritional characteristics alter dynamics of food preference in
      lambs.
AB  - We addressed two questions involving food preference. First, we determined how a
      food's flavor and nutritional characteristics affected preference. In three
      trials, we offered lambs isonitrogenous foods differing in energy (trial 1, 90%
      TDN; trial 2, 100% TDN; trial 3, 110% TDN); each food was offered in apple and
      maple flavors. We hypothesized that preference for apple- or maple-flavored food
      would decrease with increasing duration of exposure (1, 2, or 4 d), and we
      speculated that the change in preference would intensify when food contained
      inadequate or excessive levels of energy. After eating food in one flavor, lambs
      preferred the alternative flavor, even after only a 1-d exposure, and preference
      for the alternative flavor was greater when the food had inadequate or excessive
      energy (P < .05). The second experiment determined whether eating a food with
      rapidly or slowly digestible sources of energy in the morning affected lambs'
      food preferences in the evening. We speculated that lambs fed rapidly digestible
      food in the morning may prefer a slowly digestible food in the afternoon because
      slowly digestible food better maintains nutrient status throughout the night or
      because preference for the rapidly digestible food decreases after exposure in
      the morning. We offered lambs isonitrogenous and isocaloric foods, that differed
      in rates of digestion, in apple and maple flavors. Lambs fed rapidly digestible
      food in the morning preferred slowly digestible food in the alternative flavor in
      the evening. However, lambs fed slowly digestible food in either flavor in the
      morning preferred slowly digestible food in both flavors in the evening (P <
      .05). These results show that lambs' preferences change as a result of food
      ingestion, and the degree of change in preference depends on the nutritional
      characteristics of the food. These findings further suggest food intake might be
      increased by providing a variety of foods to livestock on rangelands, pastures,
      or in confinement.

PMID- 9535332
TI  - Effect of duration of feed quality restriction on body dimensions in lambs.
AB  - We measured the effect of duration of feed quality restriction and the consequent
      compensatory growth on body dimensions in 18 crossbred Swifter (Texel sire x
      Flemish dam) male lambs born in March 1994 and weaned at approximately 2 mo of
      age. The lambs were fed grass straw (46 g CP/kg DM) for ad libitum consumption
      and 35 g CP x kg(-75) x d(-1) mixed concentrates (173 g/kg DM). At approximately
      3.5 mo of age and average live weight of approximately 34 kg, the lambs were
      allotted to six blocks, each block with three lambs of approximately the same
      live weight. Within each block, the three lambs were then randomly assigned to
      two restricted treatments (R1 and R2) and a control (C) treatment. In treatments
      R1 and R2, feed quality was restricted by withholding concentrates for 3 and 4.5
      mo, respectively. A growth model was developed to study the effects of
      restriction and subsequent compensation after realimentation (6.5 and 8 mo for R1
      and R2 groups, respectively). During restriction, live weight and growth in body
      dimensions were suppressed. Bone length measures such as body length and ulna
      length were less affected than live weight. The response in testes girth to
      restriction was almost immediate. At the end of the experiment (age of about 14
      mo), R1 animals fully compensated. However, the R1 animals had higher testes
      girth (P < .001), chest girth (P < .01), and chest depth (P < .05). Extending the
      duration of feed restriction did not have a significant effect on the rate of
      losses in live weight and body dimensions during restriction. At the end of the
      experiment, except for withers height and trunk length, the R2 animals did not
      compensate fully in live weight and other dimensions. However, the parameter
      estimates suggested that the R2 animals may need a relatively longer period of
      realimentation to reach to the same size as R1 and C animals.

PMID- 9535333
TI  - Physiological adaptations in adipose tissue of Brahman vs Angus heifers.
AB  - Nonpregnant yearling Brahman (n = 12) and Angus (n = 12) heifers were equally
      allocated to two dietary treatments in a replicated study to examine responses in
      lipid metabolism to nutritional treatments consisting of a moderate energy diet
      (2.0 Mcal ME/kg) fed at maintenance and a 2.5 x maintenance high-energy diet (2.4
      Mcal ME/kg) fed for 30 d. In vitro lipogenesis and the activities of lipoprotein
      lipase (LPL) and hormone-sensitive lipase (HSL) were determined in perianal
      subcutaneous adipose tissue biopsies at the start and end of the trial. At the
      start of the trial, breeds had similar (P > .10) rates of lipogenesis and LPL
      activity. Brahman had greater (P < .05) HSL activity than Angus at the start of
      the trial and tended (P < .07) to have greater HSL activity at the end. Diet did
      not influence (P > .10) HSL activity. Heifers on the high-energy, higher-intake
      diet had greater lipogenesis (P < .001) and LPL activity (P < .01) than those on
      the moderate-energy diet. Inclusion of body condition score (BCS) nested within
      breed as a covariate explained breed differences for lipogenesis (P < .05). Thus,
      by including the covariate, the two breeds had similar (P > .10) rates of
      lipogenesis at the end of the trial. When adjusted for BCS nested within breed,
      Brahman had greater (P < .05) LPL activity than Angus.

PMID- 9535334
TI  - Bromocriptine given orally to periparturient of lactating sows inhibits milk
      production.
AB  - Gilts were assigned as controls (CTL, n = 6) or received orally 10 mg of
      bromocriptine thrice daily from d 110 of gestation until farrowing, (BRPP, n =
      7), from d 1 to 6 postpartum (PP) (BRL1, n = 6), from d 7 to 13 PP (BRL2, n = 7),
      from d 14 to 20 PP (BRL3, n = 6), or from d 21 to 27 PP (BRL4, n = 6). Weights of
      pigs were recorded at birth, 24 h later, and on d 7, 14, 21, 28, 31 (weaning),
      42, and 56 PP. Jugular blood samples were collected from sows on d 109 of
      gestation and every other day until farrowing, as well as on d 1, 6, 13, 20, and
      27 PP. Behavioral observations of sows and litters were taken every 3 min for a
      24-h period beginning 48 h after the onset of the treatments. In experimental
      sows, bromocriptine induced marked reductions in prolactin levels during
      treatment (P < .001). Compared to CTL sows, concentrations of IGF-I were higher
      at d 21 (P = .01) and 28 (P = .003) PP in BRL3 and BRL4 sows, respectively. In
      bromocriptine-treated sows, weight gain of litters was either drastically reduced
      or abolished (P < .001) during the week of treatment. Treatments also altered
      significantly the suckling behavior of pigs at all stages studied. Therefore, the
      present results strongly suggest that prolactin is essential for the initiation
      and the maintenance of milk production in sows. Results also indicate that
      prolactin does not seem to be involved in the maintenance of lactational anestrus
      during a 4-wk lactation.

PMID- 9535335
TI  - Small intestinal morphology in eight-day-old calves fed colostrum for different
      durations or only milk replacer and treated with long-R3-insulin-like growth
      factor I and growth hormone.
AB  - The effects of feeding different amounts of colostrum or only milk replacer and
      the effects of Long-R3-IGF-I (administered s.c. or orally; 50 microg/[kg BW x d]
      for 7 d), and of s.c. injected recombinant bovine GH (rbGH; 1 mg/[kg BW x d] for
      7 d) on small intestinal mucosal morphology in newborn calves were studied by
      histomorphometry. Neonatal calves fed colostrum six times exhibited greater (P <
      .01) villus circumferences, areas, and heights in total small intestine and
      especially in the duodenum than calves fed only milk replacer. Furthermore,
      villus circumferences and areas in total small intestine were greater (P < .05)
      in calves fed colostrum once than in calves fed no colostrum. Villus size in
      total small intestine was smaller (P < .05) in rbGH-treated than in control
      calves; jejunum villus circumferences and heights were especially reduced (P <
      .05). Crypt depths in ileum were greater (P < .05) in rbGH-treated calves. In
      conclusion, prolonged colostrum supply significantly enhanced small intestinal
      villus size in neonatal calves. In contrast, Long-R3-IGF-I had no significant
      influence on small intestinal morphology, and rbGH in supraphysiological amounts
      even reduced small intestinal mucosal variables after 1 wk of treatment. The
      study demonstrated enhanced postnatal development of the gastrointestinal tract
      by prolonged colostrum feeding, but not by Long-R3-IGF-I or GH.

PMID- 9535336
TI  - Breed comparison of the fatty acid composition of muscle phospholipids in Jersey
      and Limousin cattle.
AB  - We investigated the fatty acid composition of the phospholipid fraction of the
      shoulder muscle (triceps brachii) from Jersey and Limousin yearling steers,
      yearling heifers, and nonlactating cows. The aim was to study breed, sex, and age
      differences. Significant breed differences in some individual fatty acids were
      apparent between Jersey and Limousin cows. Limousin cows had more palmitate,
      vaccenate, arachidonate, and less gamma-linolenate and eicosapentanoate than
      Jersey cows. Age differences were significant: proportions of palmitate,
      stearate, and oleate decreased and linoleate, arachidonate, and total
      polyunsaturates increased with age. Most of the breed x age interactions were not
      significant. Also, phospholipids of Jersey and Limousin cows did not differ in
      total saturated, monounsaturated, and polyunsaturated fatty acids. Yearling data
      revealed significant sex differences in most of the fatty acids, including total
      monounsaturates and polyunsaturates. Yearling steers had more myristate,
      palmitoleate, stearate, and total monounsaturates and less linoleate,
      arachidonate, eicosapentanoate, and total polyunsaturates than heifers. Breed
      differences were also significant: Limousin yearlings had more di-homogamma
      linolenate and erucate and less eicosapentanoate and nervonate than their Jersey
      counterparts. The sex x breed interaction was not significant for most of the
      fatty acids. These results imply that breed, age, and sex are important factors
      that influence the fatty acid composition of muscle phospholipids in cattle.

PMID- 9535337
TI  - Relationship of visual assessments of feeder lamb muscularity to differences in
      carcass yield traits.
AB  - We examined the relationship between visual differences in muscle thickness among
      feeder lambs and subsequent differences in carcass composition. Medium-framed,
      crossbred feeder lambs (n = 120) were selected at two commercial feedlots to
      exhibit distinct phenotypic differences in muscularity. The lambs were assigned
      scores (ranging from 1 to 9; 1 = extremely thin, 5 = average, 9 = extremely
      thick) for muscle thickness and were sampled serially on d 0, 14, 28, and 42 of
      the trial. After recording yield grades, one side of each carcass was deboned,
      and the soft tissues from the entire side were ground, sampled, and analyzed for
      lipid and moisture content. The opposite side was fabricated into boneless,
      closely trimmed (.25 cm maximum fat depth) subprimal cuts. When lambs of the same
      frame size were compared at the same live weight, greater muscle thickness was
      associated with greater (P < .05) fat-free muscle mass. Correspondingly, thickly
      muscled lambs produced carcasses of a given weight that had a higher (P < .05)
      composite yield of lean meat and a lower (P < .05) proportion of trimmable fat
      compared with carcasses of thinly muscled lambs. When comparisons were made at
      the same percentage of extractable fat in the carcass, greater muscle thickness
      was associated with heavier (P < .05) live and carcass weights, increased (P <
      .05) fat-free muscle mass, and increased (P < .05) weights of trimmed, boneless
      subprimal cuts. Results suggest that visual assessments of muscle thickness in
      feeder lambs, as applied in this study, are indicative of commercially important
      differences in carcass yields of lean meat.

PMID- 9535338
TI  - The relative effectiveness of 2-hydroxy-4-(methylthio) butanoic acid and DL
      methionine in young swine.
AB  - We compared the effectiveness of 2-hydroxy-4-(methylthio) butanoic acid (HMB) and
      DL-methionine (DLM) as sources of L-methionine activity in methionine-deficient
      primary cultures of pig liver cells and methionine-deficient early-weaned pigs.
      Viable hepatocytes were obtained from minced pig liver and maintained in a high
      density, differentiated, nonproliferation cell culture system. Culture medium was
      supplemented with HMB, DLM, or L-methionine, and cells were pulse-dosed with L
      [14C(U)]leucine for 24 h to determine the level of protein synthesis. Leucine
      incorporation per milligram of protein indicated a six-to eightfold increase in
      protein synthesis (P < .01) with methionine levels between 5 and 10 microM,
      regardless of source of methionine activity. Two 24-pen replicate methionine dose
      titrations were conducted with 95 early-weaned commercial crossbred pigs. The
      pelleted corn, dried whey, and porcine plasma basal diet contained 1.5% lysine,
      .23% methionine, and .48% cystine and was supplemented with 0, .05, or .10%
      methionine activity as DLM or HMB for 21 d. There was a 134, 104, and 61%
      increase (P < .01) in cumulative ADG for each successive week on study with a 30
      and 19% improvement in feed/gain (P < .01) after 7 and 14 d. Performance
      responses due to source of methionine activity did not differ and slope ratio
      potency determinations (gain vs intake of methionine source) of HMB vs DLM
      indicated a 119, 111, and 95% relative activity for cumulative weekly
      performance. These results support the hypothesis that HMB and DLM provide
      equimolar levels of methionine activity in swine.

PMID- 9535339
TI  - Changes in pars esophageal tissue appearance of the porcine stomach in response
      to transportation, feed deprivation, and diet composition.
AB  - Experiment 1 used 48 pigs to evaluate the effect of diet particle size, fat
      content, and a 24-h fast (FST) on pars esophageal (PE) tissue damage. Following a
      FST, a 750-microm, 550-microm, or 550-microm diet with 7.9% added fat was fed for
      28 d. Additional pigs were fed the 550-microm fat-added diet with a FST every 7
      d. The initial FST induced erosion (EROS) of the PE (P < .05). A 550-microm diet
      maintained the FST-induced EROS (P < .05). The 750-microm diet allowed the PE to
      heal. Sixteen pigs were used in Exp. 2 to evaluate transportation and FST-induced
      changes in PE. A FST following transportation induced keratinization (KERT) and
      EROS of the PE (P < .05). In Exp. 3, restraint and a FST followed by a 750-microm
      diet on PE was investigated using 48 pigs. A FST induced PE KERT and EROS, which
      was reduced to pre-FST levels ( P < .05) within 3 to 14 d by a 750-microm diet.
      In Exp. 4, 70 pigs were fed 750-microm or 550-microm diets following
      transportation and subsequent FST. Within 7 d, healing (P < .05) of FST-induced
      PE damage was observed with a 750-microm diet. A 550-microm diet maintained (P <
      .05) the transportation/FST-induced PE damage. Thirty pigs were used in Exp. 5 to
      investigate the effect of restraint for 24 h and FST on PE. A FST and the
      combination of restraint and FST induced similar levels of PE damage that were
      greater than pre-restraint/FST levels (P < .05).

PMID- 9535341
TI  - Lowering the dietary calcium to total phosphorus ratio increases phosphorus
      utilization in low-phosphorus corn-soybean meal diets supplemented with microbial
      phytase for growing-finishing pigs.
AB  - Crossbred growing-finishing pigs (n = 120) were used to investigate the effect of
      three dietary Ca:total P (tP) ratios (1.5:1, 1.3:1, or 1.0:1) on P utilization in
      low-P corn-soybean meal diets supplemented with microbial phytase at 500 phytase
      units/kg. The basal grower (23 to 54 kg BW) diet contained .39% tP including .07%
      added inorganic P (iP), and the basal finisher (54 to 123 kg BW) diet contained
      .32% tP without added iP. An adequate-P positive control diet without phytase
      supplementation contained .60% Ca and .50% tP during the growing phase and .50%
      Ca and .40% tP during the finishing phase. Lowering the Ca:tP ratio linearly
      increased ADG during the growing phase (P < .03) and overall (P < .08), gain:feed
      ratio during the growing phase (P < .001), and P absorption during the finishing
      phase (P < .04). Lowering the Ca:tP ratio linearly increased BW at slaughter (P <
      .02), carcass weight (P < .04), bone breaking strength (P < .04), and bone ash
      weight (P < .06), whereas dressing percentage and backfat depth remained
      unchanged. In conclusion, pig performance and P utilization were increased by
      lowering the Ca:tP ratio from 1.5:1 to 1.0:1 in low-P corn-soybean meal diets
      supplemented with microbial phytase.

PMID- 9535340
TI  - Effects of the reproductive cycle and age on calcium and phosphorus metabolism
      and bone integrity of sows.
AB  - The purpose of this study was to determine the effects of stage of the
      reproductive cycle and age on Ca and P metabolism and bone integrity of sows.
      Five-day balance studies were conducted with first- and fifth-parity sows, and
      sows were slaughtered during the last trimester of gestation, at the end of
      lactation, or during the last trimester of the subsequent gestation. First-parity
      sows were studied during their first gestation (n = 11), first lactation (n =
      10), or second gestation (n = 10). Fifth-parity sows were examined during their
      fifth gestation (n = 10), fifth lactation (n = 9), or sixth gestation (n = 9).
      All sows were fed 1.9 kg/d of a common diet (.76% Ca and .63% P) during gestation
      and were allowed ad libitum access to the same diet during lactation.
      Digestibilities of Ca and P were much greater during lactation than during
      gestation. During gestation, young sows absorbed and retained more Ca and P than
      did mature sows. However, during lactation, mature sows consumed more feed, and
      therefore Ca and P, and retained more Ca and P than did young sows. Bones of
      mature sows were larger, more mineralized, and stronger than the bones of young
      sows. Bone weight and strength decreased during lactation and increased during
      the subsequent gestation. Changes in weight and strength were greater in young
      sows than in mature sows.

PMID- 9535342
TI  - Effect of protein levels and space allocations on performance of growing
      finishing pigs.
AB  - We conducted two trials with growing-finishing pigs (Pig Improvement Company line
      405 x Camborough 15) to evaluate the effects of space allocation on performance
      and CP requirements. In Trial 1, a 2 x 3 factorial (two levels of space, three CP
      regimens) was used with 252 pigs. Pigs were allocated to either .23, .28, .37, or
      .50 m2 per pig (crowded) or .37, .47, .60, or .74 m2 per pig (uncrowded) during
      the 18 to 36, 36 to 55, 55 to 91, and 91 to 127 kg weight periods, respectively.
      Diets contained 16.1, 18.6, or 21.1% (18 to 36 kg), 15.3, 17.8, or 20.3% (36 to
      55 kg), 14.7, 17.2, or 19.7% (55 to 91 kg), and 12.8, 15.3, or 17.8% (91 to 127
      kg) CP. The 16.1, 15.3, 14.7, and 12.8 % CP (control) diets contained 1.09, .86,
      .82, and .65% lysine, respectively. Crude protein levels (Trials 1 and 2) were
      achieved by substituting soybean meal for corn. In Trial 1, a CP x space
      interaction ( P < .03) for gain:feed suggested that feed efficiency of grower
      pigs was improved to a greater extent in uncrowded pigs than in crowded pigs.
      Grower pigs (18 to 55 kg) with less space had depressed (P < .05) feed intake and
      gain and a lower (P < .10) feed efficiency than uncrowded pigs. Added CP improved
      (P < .05) rate and efficiency of gain in grower pigs. Overall (18 to 127 kg),
      crowded pigs had reductions (P < .05) in gain (17.6%), feed intake (11.3%), and
      gain:feed ratio (7.1%) compared to uncrowded pigs. Trial 2 involved 216 finishing
      pigs in a 2 x 2 factorial (two levels of space, two CP regimens). Pigs were
      provided with either .37 or .50 m2 per pig (crowded) and .60 or .74 m2 per pig
      (uncrowded) during the 55 to 91 and 91 to 127 kg weight periods, respectively.
      The diets contained 14.1 or 17.1% CP (55 to 91 kg) and 12.1 or 15.1% CP (91 to
      127 kg). Lysine levels were .67 and .53% for the 14.1 and 12.1% CP diets,
      respectively. Overall (55 to 127 kg), crowded pigs had depressed (P < .05) gains
      (15.4%), feed intakes (9.5%), and feed efficiencies (6.8%) compared with
      uncrowded pigs. Increasing CP resulted in improved (P < .05) ADG (7.4%) and
      gain:feed (8.3%) in crowded and uncrowded pigs. The data suggest that pigs with
      lower feed intakes as a result of space restrictions do not have higher CP
      requirements than those with more space.

PMID- 9535343
TI  - Hepatic metabolism of skatole in pigs by cytochrome P4502E1.
AB  - High concentrations of skatole in fat are a major cause of boar taint in intact
      male pigs. Skatole is metabolized in the liver, and this metabolism could affect
      concentrations of skatole in fat. In this study, we evaluated the involvement of
      cytochrome P450, in particular cytochrome P4502E1, in skatole metabolism in pig
      liver. Liver microsomes from F4 European Wild Pig x Swedish Yorkshire intact male
      pigs were incubated in a buffer containing NADPH, NADH, and skatole. Several
      skatole metabolites were detected by HPLC, including 6-hydroxyskatole (pro-MII),
      3-hydroxy-3-methyloxyindole (MIII), and five others not identified in this study.
      Inhibitors of P450 were added to microsomal incubations, and their effect on the
      formation of skatole metabolites and skatole disappearance was evaluated. The
      general cytochrome P450 inhibitors SKF 525A, at a concentration of .2 mM and
      metyrapone, at a concentration of .1 mM decreased the formation of pro-MII (P =
      .001) to 38.2 and 11.6%, respectively, of that of controls. The SKF 525A also
      reduced the synthesis of MIII and three other metabolites, whereas metyrapone
      only reduced the disappearance of skatole and synthesis of pro-MII. Inhibitors
      specific for cytochrome P4502E1 were more effective in reducing the formation of
      skatole metabolites than SKF 525A and metyrapone. Chlorzoxazone and diallyl
      sulfide reduced (P = .001) the synthesis of pro-MII to 9.7 and 30.9% of the
      control rate. The formation of most of the other skatole metabolites and
      disappearance of skatole were also reduced with these inhibitors. These results
      indicate that skatole is metabolized in pig liver to pro-MII and other
      metabolites by cytochrome P4502E1.

PMID- 9535344
TI  - Relationship between oxidation and conjugation metabolism of skatole in pig liver
      and concentrations of skatole in fat.
AB  - High concentrations of skatole in fat of some intact male pigs are a major cause
      of boar taint. In this study, we investigated the effect of oxidative and
      conjugative metabolism of skatole in liver on the concentrations of skatole in
      the fat of intact male pigs. In Trial 1, 18 Yorkshire intact males were equally
      divided into two treatments with high (mean, .42; SD, .26 ppm) and low (mean,
      .06; SD, .02 ppm) fat skatole levels. There was an increased rate of skatole
      metabolism, an increased glucuronidation activity, and a decreased sulfation
      activity toward 2-naphthol in liver from pigs with high skatole levels (P < .05).
      In Trial 2, Swedish Yorkshire x F4 European Wild Pig intact males were used.
      Among skatole metabolites that were produced in incubations with liver
      microsomes, pro-MII was conjugated with glucuronic acid and sulfate, and
      metabolite F-1 was conjugated with glucuronic acid. The rates of formation of
      various skatole metabolites and conjugation of pro-MII were evaluated for 22 pigs
      with different levels of cytochrome P4502E1 in the liver. The formation of F-1
      and sulfation of pro-MII were negatively correlated with fat skatole levels (r = 
      .59, and r = -.56, respectively) and were decreased in pigs with high fat skatole
      levels and low P4502E1 levels (P < .01). The results indicate that oxidation and
      conjugation reactions of skatole in pig liver have a dramatic effect on skatole
      levels in the fat. In particular, the formation of F-1 and formation and
      subsequent sulfation of pro-MII are related to low levels of skatole in the fat,
      presumably due to rapid metabolic clearance of skatole.

PMID- 9535345
TI  - Immunocytochemical localization of luteinizing hormone and follicle-stimulating
      hormone in the equine pituitary.
AB  - Gonadotropin-specific primary antisera and gold-conjugated secondary antibodies
      were used to immunocytochemically localize gonadotropins in the anterior
      pituitary of intact pony mares. Electron microscopy was then used to characterize
      the ultrastructure and immunoreactive staining characteristics of equine
      gonadotropes. Cells containing LH were morphologically indistinguishable from
      those containing FSH. Gonadotropes were relatively large and commonly had
      eccentric nuclei. The rough endoplasmic reticulum was well developed and dilated.
      Secretory granules were present in two morphologically distinct forms. Large
      polymorphic granules were generally located in perinuclear cytoplasmic areas,
      whereas small and uniformly shaped granules were in the peripheral cytoplasm,
      close to the cell membrane. Double-labeling revealed cells with granules that
      stained for both LH and FSH as well as cells that stained for either LH or FSH.
      Gonadotropes constituted 15 to 32% of all pituitary cells in the anterior
      pituitaries from the three mares included in this study. Cells that stained for
      only LH constituted 2 to 16% of all pituitary cells, cells that stained for only
      FSH ranged from 1 to 4.5%, and cells staining for both hormones constituted 6.2
      to 24% of the pituitary cells. These results indicate that there are in fact
      three distinct subclasses of gonadotropes in the equine anterior pituitary based
      on immunocytochemical staining, which is similar to the situation described for
      several other mammalian species.

PMID- 9535346
TI  - Technical note: Application of the Box-Cox data transformation to animal science
      experiments.
AB  - In the use of ANOVA for hypothesis testing in animal science experiments, the
      assumption of homogeneity of errors often is violated because of scale effects
      and the nature of the measurements. We demonstrate a method for transforming data
      so that the assumptions of ANOVA are met (or violated to a lesser degree) and
      apply it in analysis of data from a physiology experiment. Our study examined
      whether melatonin implantation would affect progesterone secretion in cycling
      pony mares. Overall treatment variances were greater in the melatonin-treated
      group, and several common transformation procedures failed. Application of the
      Box-Cox transformation algorithm reduced the heterogeneity of error and permitted
      the assumption of equal variance to be met.

PMID- 9535347
TI  - Duration of treatment with progesterone and regression of persistent ovarian
      follicles in cattle.
AB  - The objective of the present study was to determine the duration of elevated
      concentrations of progesterone necessary to induce atresia of persistent ovarian
      follicles. Heifers were administered 25 mg of PGF2alpha on d 6 and 7 (d 0 = d of
      synchronized estrus) and a norgestomet implant from d 6 to 14. Ovaries were
      monitored by ultrasonography, and blood samples were collected on d 3, 5, 7, 9,
      11, and 12 and daily from d 14 until ovulation. On d 12, heifers received either
      two progesterone-releasing intravaginal devices (PRID) for 6 h (6-h; n = 5), two
      PRID for 24 h (24-h; n = 5), or no treatment (CON; n = 5). Blood samples were
      collected at 15-min intervals from h -6 to 30 (PRID insertion = h 0) and analyzed
      for concentrations of LH. Characteristics of LH secretion were determined for
      consecutive 6-h periods (Period 0 to 5). Hourly blood samples, collected from h 0
      to 29, were analyzed for concentrations of 17beta-estradiol (estradiol) and
      progesterone. The dominant ovarian follicles present on d 7 increased in size to
      15.4+/-.3 mm on d 12 ("persistent follicle"). Following removal of the PRID and
      norgestomet implants, atresia of persistent follicles and ovulation of new
      follicles were induced in one of five and in four of five heifers in the 6-h and
      24-h treatments, respectively. Persistent follicles ovulated after withdrawal of
      norgestomet in all other heifers. Concentrations of progesterone were increased
      from h 1 to 7 in the 6-h and h 1 to 26 in the 24-h treatment. Frequency of LH
      pulses was reduced (P < .05) during Periods 1 to 2 in the 6-h and Periods 1 to 5
      in the 24-h treatment relative to the CON treatment. By h 10, concentrations of
      estradiol in the 6-h and 24-h treatments were lower (P < . 05) than in the CON
      treatment. This suppression continued through h 29 in the 24-h treatment (P <
      .05), whereas concentrations in the 6-h treatment were intermediate to those of
      the CON and 24-h treatments after h 14. Suppression of pulsatile LH release and
      estradiol secretion was evident with 6 and 24 h of treatment with progesterone,
      but only the 24-h treatment induced atresia of persistent follicles in a majority
      of the heifers.

PMID- 9535348
TI  - Influence of feed restriction during lactation on gonadotropic hormones and
      ovarian development in primiparous sows.
AB  - Effects of nutritional deficit during lactation on secretion of gonadotropic
      hormones and ovarian follicular populations around weaning were investigated in
      24 primiparous crossbred sows. Sows were allocated to receive close to ad libitum
      intakes (H) or approximately 50% of this amount (L) during a 28-d lactation.
      Serial blood samples were collected 1 d before weaning (W-1), in the hours
      following weaning (W), and 1 d after (W+1). Their ovaries were removed on the day
      of weaning or 2 d later (W+2) and subjected to macroscopic and histological
      observations. Mean and basal LH concentrations were not influenced by the level
      of feeding. Frequency of LH pulses was reduced in L sows (.17, .5, and .5 vs
      1.50, 1.17, and .83 pulses/6 h at d W-1, W, and W+1 respectively; P < .05). Mean
      and basal concentrations of LH were influenced by the day of sampling, being
      significantly increased within hours following weaning. Mean FSH concentrations
      were influenced neither by the level of feeding nor by the day of sampling. At
      weaning, the ovaries from L sows were lighter and had smaller follicles and fewer
      follicles > or = 4 mm (P < .05). Values of these macroscopic characteristics
      increased after weaning ( P < .05). At weaning, the percentage of healthy
      follicles was higher in the first class (< 1 mm) and lower in the second class (1
      to 2.99 mm) in L compared to H sows (P < .05). Whatever the day of sampling, IGF
      I concentrations in follicular fluid tended to be lower in L than in H sows.
      These results indicate that feed restriction during lactation inhibits LH
      pulsatility and ovarian activity.

PMID- 9535349
TI  - Fat supplementation influences postpartum reproductive performance in Brahman
      cows.
AB  - Multiparous Brahman cows (n = 40) in excellent body condition (6.5+/-.1) were
      randomly assigned to receive either 5.2 (rice bran) or 3.7% (control) dietary fat
      after calving. The experimental diets were formulated to be isocaloric and
      isonitrogenous. The experimental diets were fed twice daily from d 1 after
      calving through the first normal estrous cycle. Cows were weighed, scored for
      body condition, and bled at weekly intervals from d 1 through 50 after calving.
      Weekly bleedings continued until the first detectable estrus. Blood samples were
      collected daily throughout the first normal estrous cycle. All cows were exposed
      to a fertile bull at the estrus following the first normal estrous cycle and for
      a 60-d breeding season. Ovarian follicular populations were recorded weekly by
      transrectal ultrasonography from d 15 to 50 after calving. Calf weights were
      recorded at 14-d intervals from d 1 to 43 after birth and at weaning (205 d).
      Cows receiving rice bran gained more body condition (P < .05) than cows receiving
      the control supplement. The numbers of small (< 4.0 mm, P < .05), medium (4.0 to
      7.9 mm, P < .05) and total follicles (P < .05) were greater in the rice bran than
      in the control group from 15 to 29 d after calving, and large follicles ( > or =
      8.0 mm) increased in number (P < .05) and the largest follicle increased in size
      (P < .001) over time regardless of the level of dietary fat. Fat supplementation
      increased the numbers of medium (P < .01), large (P < .05), and total (P < .01)
      follicles and size of the largest follicle (P < .05) during the 3 wk before the
      first normal estrous cycle. The intervals from parturition to reproductively
      important end points were similar (P > .10) between dietary treatments as well as
      the percentage of cows showing normal or abnormal estrous cyclic activity.
      Treatment did not affect (P > .10) daily serum progesterone (P4) concentrations.
      However, there was a tendency (P = .09) for more rice bran-supplemented cows to
      be pregnant (94.1 vs 71.4%) after being exposed to a fertile bull for 60 d. Calf
      weight gain tended to be higher (P = .08) in calves nursing rice bran
      supplemented dams. In conclusion, using rice bran, with high concentrations of
      oleic and linoleic acids, as a fat supplement for postpartum cows enhanced
      ovarian follicular growth before normal estrous cycles resumed and increased body
      condition scores and pregnancy rates without altering postpartum interval or
      serum P4 concentrations.

PMID- 9535350
TI  - Influence of hypo- or hyperthyroidism on ovarian function in Brahman cows.
AB  - Multiparous Brahman cows (n = 21) were randomly assigned during late fall within
      BW and body condition score (BCS) to receive either 3.0 mL of corn oil (C; n =
      7), 3.0 mg/(cow x d) triiodothyronine (T3) s.c. in 3.0 mL of corn oil (HYPER; n =
      7), or 4.0 mg/(kg x d) 6-n-propyl-2-thiouracil (PTU; fed with concentrate) plus
      3.0 mL/d corn oil (HYPO; n = 7). Water, minerals, and Coastal bermudagrass hay
      were available free choice, and all cows received 3.2 kg x cow(-1) x d(-1) of 5:1
      corn:soybean meal concentrate. The feeding period extended through three normal
      estrous cycles. Blood samples were collected weekly during the first and second
      estrous cycle, or until d 42 for anestrous cows, and daily throughout the third
      cycle. Also, between d 9 and 14 of the third cycle, or after d 35 in anestrous
      cows, intensive samples were collected at 2-h intervals for 24 h. Serum T3,
      thyroxine (T4), and progesterone (P4) were measured in weekly and intensive
      samples, and cortisol, insulin, GH, and thyroid-stimulating hormone (TSH) were
      measured in intensive samples. The altered thyroid status of HYPER and HYPO cows
      was evident (P < .001) during the third estrous cycle in mean daily T3, T4, and
      intensive TSH (P < .001) concentrations. Changes in BW and BCS were influenced by
      treatment (P < .001). A greater (P < .001) proportion of HYPER cows exhibited
      abnormal cycle length, and three of seven cows became anestrous. For cows that
      continued normal cycles, treatment did not affect (P > .05) the number of
      follicular waves, diameter of the dominant follicle, diameter of the ovulatory
      follicle, or P4 profiles during the third cycle. Insulin and GH concentrations
      did not differ (P > .05) among treatments in intensive samples, but, mean
      cortisol was greatest (P < .02) in HYPER cows. For Brahman cows that maintained
      normal estrous cycles, induced hyper-or hypothyroid status did not influence
      ovarian function.

PMID- 9535351
TI  - Intake and digestion by Holstein steers consuming diets based on litter harvested
      after different numbers of broiler growing periods or with molasses addition
      before deep-stacking.
AB  - We determined the effects on feed intake and digestibility by Holstein steers of
      1) the number of broiler growing periods before litter harvest and dietary level
      of broiler litter and 2) level of molasses added to broiler litter before deep
      stacking. In Exp. 1, eight steers (179+/-7.4 kg average BW) were used in two
      simultaneous 4 x 4 Latin squares (2 x 4 factorial) with 21-d periods. Broiler
      litter harvested after one, three, or six 6-wk growing periods (1P, 3P, and 6P,
      respectively) mixed with .5 or 1.5% BW of ground corn (.5C and 1.5C,
      respectively) was consumed ad libitum. Bermudagrass hay was fed to 1P, 3P, and 6P
      steers at .5% BW and was ingested ad libitum by Control steers, along with
      feeding of .5 or 1.5% BW of corn (DM basis). Broiler litter was 63, 43, and 35%
      NDF, 2.2, 3.5, and 4.1% N, and 18, 30, and 27% ash for 1P, 3P, and 6P,
      respectively. Total tract digestibility of NDF was 53.7, 29.4, 50.4, 58.1, 31.3,
      30.8, 34.1, and 49.5% (SE 3.50), and digestible OM intake was 2.21, 1.70, 2.27,
      2.39, 2.26, 3.18, 2.93, and 3.34 kg/d (SE .160) for .5C-Control, .5C-1P, .5C-3P,
      .5C-6P, 1.5C-Control, 1.5C-1P, 1.5C-3P, and 1.5C-6P, respectively. In Exp. 2,
      five steers (228+/-6.0 kg average BW) were used in a 5 x 5 Latin square with 21-d
      periods. Offered diets were 15% bermudagrass hay and 60% broiler litter (6P of
      Exp. 1; DM). Molasses was offered at 0, 3.2, or 6.7% of total DM, with the
      balance of the diet composed of corn. Molasses for two treatments was mixed with
      litter at meals, whereas for two other treatments molasses and litter were mixed
      before deep-stacking. Only a few minor treatment effects on intakes and
      digestibilities occurred. In conclusion, digestible OM intake by growing steers
      was less for litter harvested after one broiler growing period than after three
      or six when fed with only .5% BW of corn, although the effect of the number of
      periods was negligible with corn given at 1.5% BW. Molasses addition before deep
      stacking or at meals did not enhance feeding value of litter harvested after six
      broiler growing periods.

PMID- 9535352
TI  - Ensiling effects of the ethanol fractionation of forages using gas production.
AB  - We studied the use of gas curve subtraction to distinguish between two fractions
      soluble in neutral detergent solution. Samples of unfractionated (whole) forage,
      residue insoluble in 90% ethanol, and isolated NDF were fermented in vitro, and
      gas production was monitored. The gas volume associated with the ethanol solubles
      (A fraction) was determined as the difference between the gas from the whole
      forage and from the ethanol residue. The gas yield associated with the fraction
      insoluble in 90% ethanol but soluble in neutral detergent solution (B fraction)
      was determined by subtracting the isolated NDF gas curve from the corresponding
      ethanol residue curve. This experiment included three forages (alfalfa,
      bromegrass, and orchardgrass) harvested at two maturities and preserved by freeze
      drying or ensiling to form a 3 x 2 x 2 factorial arrangement. Ensiling reduced
      the rate of gas formation from the A fraction by approximately 30% (P < .01).
      Ensiling increased (P < .05) the size of the A fraction (2 to 10% of DM) but did
      not change the volume of gas produced (P > .05). The gas yield from the B1
      fraction was reduced 40% (P < .05) by ensiling with no significant change in
      rate. Curve subtraction of gas production profiles may be used to obtain rate
      estimates for multiple neutral detergent soluble pools. The separation of the
      neutral detergent solubles into two pools clarified the effects caused by
      ensiling. Changes due to ensiling on the rate of gas produced were associated
      with the A fraction, and the effects on final gas volume were associated with the
      B1 fraction.

PMID- 9535353
TI  - Efficiency of energy and nitrogen loss and gain in mature cows.
AB  - Our objective was to quantify the energy and nitrogen balances of mature cows fed
      a fixed amount of forage. Six cows were assigned to each of two treatments. At
      time 0, control cows received 83.55+/-.52 g of chopped brome hay x (BWkg)(-.75) x
      d(-1). Feed intake remained fixed (9,103+/-277 g/d) over the entire 224 d of the
      study. At time 0 treated cows received 82.10+/-1.26 g of chopped brome hay x
      (BWkg)(-.75) x d(-1) (9,083+/-113 g/d). After time 0, treated cows were offered
      65% of the time-0 feed intake for the first 112 d (Phase 1) and 135% of the time
      0 feed intake for the last 112 d (Phase 2). Treatments were designed so that the
      total amount of feed received during the 224 d was the same for each treatment.
      Additional balance measurements were made on d 28, 56, 84, 112, 140, 168, 189,
      and 224. Although treatment groups differed within phases for cumulative heat
      production, control cows did not differ from treated cows in total heat produced
      during the 224-d study (P = .60). Net retained energy over the entire 224-d
      period did not differ between treatments (P = .43). Treated animals retained more
      nitrogen than did control animals (P = .008). The increased efficiency of
      nutrient utilization during refeeding in cows allowed to fluctuate in weight
      offers the potential to develop feeding strategies that improve grazed forage
      utilization and reduce supplemental feed.

PMID- 9535354
TI  - Methane output and lactation response in Holstein cattle with monensin or
      unsaturated fat added to the diet.
AB  - We measured effects of continuous vs twice-daily feeding, the addition of
      unsaturated fat to the diet, and monensin on milk production, milk composition,
      feed intake, and CO2-methane production in four experiments in a herd of 88 to
      109 milking Holsteins. Methane and CO2 production increased with twice-daily
      feeding, but the CO2:CH4 ratio remained unchanged. Soybean oil did not affect the
      milkfat percentages, but fatty acid composition was changed. All saturated fatty
      acids up to and including 16:0 decreased (P < .01), whereas 18:0 and trans 18:1
      increased (P < .001). The 18:2 conjugated dienes also increased (P < .01) when
      the cows were fed soybean oil. Monensin addition to the diet at 24 ppm decreased
      methane production (P < .01); the CO2:CH4 ratios reached 15, milk production
      increased (P < .01), and milkfat percentage and total milkfat output decreased (P
      < .01), as did feed consumption, compared with cows fed diets without monensin (P
      < .05). Milk fatty acid composition showed evidence of depressed ruminal
      biohydrogenation: saturated fatty acids (P < .05) decreased and 18:1 increased (P
      < .001); most of the increase was seen in the trans 18:1 isomer. As with soybean
      oil feeding, addition of monensin also increased (P < .05) the concentration of
      conjugated dienes. The monensin feeding trial was repeated 161 d later with 88
      cows, of which 67 received monensin in the diet in the first trial and 21 cows
      were newly freshened and had never received monensin. Methane production again
      decreased (P < .05), but this time the CO2:CH4 ratio did not change and all other
      monensin-related effects were absent. The ruminal microflora in the cows that had
      previously received monensin seemed to have undergone some adaptive changes and
      no longer responded as before.

PMID- 9535355
TI  - The very-long-chain acyl-coA dehydrogenase gene maps to pig chromosome 12.

PMID- 9535356
TI  - Partial clone and sequence of an ovine glyceraldehyde-3-phosphate dehydrogenase
      cDNA.

PMID- 9535357
TI  - A HincII polymorphicn in the porcine calpain, large polypeptide L3 (CAPN3) gene.

PMID- 9535358
TI  - Direct coronary stenting without predilatation: a new therapeutic approach with a
      special balloon catheter design.
AB  - Coronary stenting is the primary therapeutic option for many coronary lesions,
      after the risk of subacute stent thrombosis and bleeding complications has been
      reduced by antithrombotic regimens and improved stent expansion. It would be
      desirable to shorten the procedure and the duration of ischemia, and to reduce
      the risk of ischemic complications during balloon inflation by implanting the
      stent without previous dilatation of the lesion. This is not possible with the
      presently available stent delivery systems. This new therapeutic concept was
      tested with a specially designed balloon catheter, on which slotted-tube stents
      can be fixed between two conical radiopaque markers. Sixty-one patients eligible
      for angioplasty underwent direct stent implantation without predilatation. Four
      procedures were performed for acute myocardial infarction, and two as high-risk
      PTCA. Single slotted-tube stents (Palmaz-Schatz, NIR, or JOStent) of 14-16-mm
      length were mounted between the conical radiopaque markers of a special balloon
      which provided a fixation for the crimped stent. The direct implantation was
      successful in 80% of all patients, while in 10% the stent could be deployed after
      predilatation of the lesion. In 10% of lesions a stent could not be implanted
      with this and any other delivery system. When patients with successful direct
      stenting were compared with those with indirect (after predilatation) or
      unsuccessful stent deployment, the presence of angiographically visible
      calcification was higher in the unsuccessful cases (75% vs. 19%; P < 0.01), and
      the patients were older (72+/-8 vs. 61+/-12 years; P < 0.01). Radiation exposure
      time was only 8.7+/-5.1 min as compared with 12.6+/-7.6 min in conventional stent
      procedures with predilatation (P < 0.05). The number of balloons used per lesion
      was also lower than with conventional stenting. Stent dislocation was observed in
      5%, and no embolization occurred. The new therapeutic approach of direct stenting
      without predilatation proved to be a safe and successful procedure in this
      initial series of coronary angioplasties. When calcified coronary lesions are
      avoided, it provides a way to rationalize stent implantation with shorter
      radiation exposure times, fewer balloons, and the potential advantage of fewer
      ischemic complications as no balloon predilatation is required.

PMID- 9535359
TI  - ECG-gated versus nongated three-dimensional intracoronary ultrasound analysis:
      implications for volumetric measurements.
AB  - The quantitative analysis of a three-dimensional (3-D) intracoronary ultrasound
      (ICUS) image data set permits a more comprehensive assessment of coronary
      arterial segments. The 3-D image sets are generally acquired during continuous
      motorized pullbacks. However, the cyclic changes of vascular dimensions and the
      cyclic spatial displacement of the ICUS transducer relative to the vessel wall
      can result in characteristic image artifacts, which may limit the applicability
      of quantitative automated analysis systems. This limitation may be overcome by an
      ECG-gated image acquisition. In the present study we acquired in vivo (1)
      nongated and (2) ECG-gated 3-D ICUS image sets of 15 human atherosclerotic
      coronary arteries and performed a computer-assisted contour detection of the
      lumen and total vessel boundaries. Total vessel and lumen volumes measured
      significantly larger in the nongated versus ECG-gated end-diastolic image sets
      (753+/-307 mm3 vs. 705+/-305 mm3; 411+/-154 mm3 vs. 388+/-165 mm3, both: P <
      0.05). Both end-diastolic and systolic measurements were available in nine
      arteries, showing a larger total vessel and lumen volume at systole (664+/-221
      mm3 vs. 686+/-227 mm3, P=0.03; 384+/-164 mm3 vs. 393+/-170 mm3, P=0.08). The
      differences observed may be of particular interest for volumetric ICUS studies,
      addressing presumably small differences in vessel or lumen dimensions.

PMID- 9535360
TI  - What's new with IVUS?

PMID- 9535361
TI  - Correlation of residual stenosis immediately after coronary angioplasty with long
      term prognosis.
AB  - This study evaluated the correlation of residual stenosis after percutaneous
      transluminal coronary angioplasty with the long-term prognosis. Among consecutive
      1,230 patients who underwent coronary angioplasty in the National Cardiovascular
      Center in Osaka, Japan, 894 patients had de novo lesions. Of these, the 70
      patients with acute myocardial infarctions and 105 with unstable angina who had
      emergency coronary angioplasties were excluded from the study. Among the
      remaining 719 patients, successful dilatation of the main target vessel was
      achieved in 592 patients, who then comprised the study group. They were divided
      into three groups according to their residual stenosis (RS) immediately after
      coronary angioplasty: group A, RS < 15% (n=208); group B, 15% < or = RS < or =
      35% (n=286), and group C, 35% < RS < 50% (n=98). The duration of follow-up was
      1,668, 1,660, and 1,680 days in group A, B, and C, respectively. The groups A, B,
      and C were not significantly different in terms of age, history of myocardial
      infarction, left ventricular ejection fraction, number of diseased vessels and
      target vessels, and risk factors such as hypertension, hyperlipidemia, and
      diabetes mellitus. Primary end point of follow-up was defined as death from any
      cause and the second end point was occurrence of cardiac events. Kaplan-Meier
      survival analysis showed significant differences among the three groups.
      Moreover, survival curves seem to be dependent on the degree of post-procedural
      residual stenosis. Multivariate analysis using a Cox proportional hazard
      regression model showed that age, ejection fraction, and residual stenosis were
      independent determinants of event-free, cardiac, and total survival. Residual
      stenosis immediately after coronary angioplasty is an independent contributor to
      long-term clinical prognosis in patients treated with successful balloon coronary
      angioplasty.

PMID- 9535362
TI  - Smaller isn't bigger.

PMID- 9535363
TI  - Dissection of the aortic sinus of Valsalva complicating coronary catheterization:
      cause, mechanism, evolution, and management.
AB  - We have rarely observed the appearance of a dissection of the aortic sinus of
      Valsalva during catheterizations of the related coronary artery. The aim of this
      study is to describe the cause, mechanism, and evolution of this complication,
      which have implications for the management of the patient. According to our
      experience (one case out of 12,546 diagnostic and three cases out of 4,970
      angioplasty procedures performed during the last 6 years), the dissection of the
      sinus of Valsalva always results from the retrograde extension of a dissection of
      the right coronary artery. It usually remains localized, but it may quickly
      involve the entire aorta. Contrast injections and balloon inflations promote its
      propagation, so these procedures should be avoided if possible. Instead of
      angiography, transesophageal echocardiogram is a safe and accurate method for
      studying its extension and as a follow-up method. The sinus of Valsalva
      dissections that remain localized during catheterization tend to spontaneously
      resolve in the first month.

PMID- 9535364
TI  - Geeez! Oh my God! Oops! #&*&!.

PMID- 9535365
TI  - Cerebral blood flow velocities monitored by transcranial Doppler during cardiac
      catheterizations in children.
AB  - Transcranial Doppler (TCD) was used to evaluate brain circulation during cardiac
      catheterizations in 32 children requiring pulmonary (n=10) or aortic balloon
      dilatations (n=2), ductus arteriosus coil insertions (n=5), or angiography
      (n=15). Cerebral blood flow velocity (CBFV) in the middle cerebral artery was
      measured before (baseline), during, and after each procedure (mean+/-95%ci). High
      intensity transient signals (HITS) were also detected during these maneuvers.
      Balloon angioplasty decreased CBFV by 63+/-11% from baseline (P < 0.01). Shorter
      durations of the inflation cycle resulted in earlier CBFV recovery (r=0.78).
      During angiography, CBFV increased by 11+/-4% (P < 0.01) in all except one case
      that showed retrograde diastolic flow. Mean total HITS count was 44
      (95%ci.limits: 27,74). These signals were more frequently found in septal defects
      or systemic arterial manipulations. Pediatric cardiac catheterization may impose
      transient fluctuations in brain perfusion as indicated by TCD, but their clinical
      implications are uncertain. CBFV changes during balloon angioplasty emphasize the
      importance of rapid inflation/deflation cycles. TCD can monitor such changes and
      evaluate preventive measures.

PMID- 9535366
TI  - Transcatheter closure of secundum atrial septal defect in a patient with
      dextrocardia using the amplatzer septal occluder.
AB  - Transcatheter closure of secundum atrial septal defects (ASD) in patients with
      levocardia is performed routinely using various investigational devices. A 6-yr
      old child with dextrocardia, situs inversus, and secundum ASD measuring 13 mm by
      TEE underwent successful transcatheter closure using a 15 mm Amplatzer Septal
      Occluder with complete closure of the defect.

PMID- 9535367
TI  - Eradicating acute hemolysis following transcatheter closure of ductus arteriosus
      by immediate deployment of a second device.
AB  - Two patients who underwent transcatheter closure of patent ductus arteriosus, one
      with a Rashkind umbrella device and the other with a coil, suffered from acute
      hemolysis following the procedure. Hemolysis ceased after deployment of second
      device(s) within 48 hr without needing to retrieve the first devices in either
      patient. We conclude that immediate deployment of a second device(s) is an
      alternative to surgery when acute hemolysis occurs following transcatheter
      closure of ductus.

PMID- 9535368
TI  - Analysis of vessel wall morphology, blood flow velocity, and the hemostatic
      system in a patient with a large intracoronary thrombus.
AB  - A patient with AMI caused by a large thrombus in the proximal LAD was
      successfully treated with PTCA and an intracoronary lysis combined with the
      platelet-receptor antagonist c7E3. Analysis of cellular hemostasis after 1 and 6
      months revealed a sustained platelet activation despite combined anti-platelet
      therapy with ASA and ticlopidine. A progredient slow-flow phenomenon appeared
      during control angiographies, confirmed by intracoronary Doppler examination.

PMID- 9535369
TI  - Intracoronary embolization and retrieval of radio-opaque ring marker on the ACS
      Multi-Link stent sheath.
AB  - We report a case of intracoronary embolization of a ring marker on a stent
      sheath. The Microsnare device was unsuitable because of the distal position of
      the marker. After failing to retrieve the marker using an over-the-wire balloon
      and the two-wire technique, we succeeded in removing the marker using a balloon
      on-wire system.

PMID- 9535370
TI  - Percutaneous closure of a coronary aneurysm with a vein-coated stent.
AB  - Coronary artery aneurysm is a rare but recognized complication following
      percutaneous intervention. We report the formation of such an aneurysm after
      recanalization with Excimer laser wire of a chronic totally occluded left
      anterior descending coronary artery and stent implantation and its subsequent
      treatment using an autologous vein graft-coated stent.

PMID- 9535371
TI  - Delayed appearance of distal coronary perforation following stent implantation.
AB  - Coronary perforations are usually apparent immediately after the occurrence. We
      report a case of a 67-year-old woman where coronary perforation presented 16
      hours after the procedure. This case illustrates the need for extra vigilance and
      careful evaluation of distal vasculature while using stiff coronary guidewires.

PMID- 9535372
TI  - Hemodynamic rounds series II: mitral stenosis and pulsus alternans.

PMID- 9535373
TI  - Total reconstruction of a diseased saphenous vein graft by means of conventional
      and autologous tissue-coated stents.
AB  - This is the first report of a total reconstruction of a diseased saphenous vein
      graft, with thrombus-containing lesion and multiple stenoses, by the implantation
      of arterial graft- and venous graft-coated stents, and of conventional stents.
      The procedure was successful without any complications, and follow-up angiography
      after 6 months revealed patency of the vessel.

PMID- 9535374
TI  - Reconstructing diseased vein grafts--great potential raises old issues.

PMID- 9535375
TI  - Modified "T" stenting: a technique for kissing stents in bifurcational coronary
      lesion.
AB  - The kissing stenting using a new technique in two patients is reported. A stent
      was positioned at the ostium of the side branch. Another stent was advanced into
      the main vessel until the center of the stent was positioned near the origin of
      the side branch. The stent at the ostium of the side branch was deployed and the
      balloon and the guidewire were removed from the side branch. Thereafter, the
      stent in the main vessel was deployed. The follow-up angiogram of those patients
      showed no restenosis in both the vessels.

PMID- 9535376
TI  - Stenting after thrombectomy with the AngioJet catheter for acute myocardial
      infarction.
AB  - The presence of massive intracoronary thrombi may contraindicate stenting. The
      AngioJet catheter rheolytic thrombectomy prepared the road for an easy and
      uneventful stenting in 2 patients with acute myocardial infarction (AMI) and
      thrombi. This combination provides a promising strategy for patients with AMI and
      angiographic evidence of massive thrombi.

PMID- 9535378
TI  - Importance of French size in percutaneous transluminal coronary angioplasty.

PMID- 9535377
TI  - Six French sheathless coronary angioplasty using a novel technique to introduce
      the guiding catheter: the INTRUC, a preliminary retrospective study.
AB  - This registry describes our preliminary experience with a novel introducing
      catheter allowing direct percutaneous introduction of the 6F guiding catheter (G
      C), minimizing the puncture size, preventing vessel scraping, and improving the
      pushability and torque response of the G-C. In 1995, 203 patients had sheathless
      PTCA, using this device. Eighty-five percent were male. Mean age was 65+/-10
      years. Thirty-nine percent had stable angina, 35% unstable angina, 7% evolving
      infarction, and 19% recent infarction. Two hundred fifty-six lesions were treated
      (1.26/patient). One hundred eight patients (52%) received one (85%) or more than
      one (15%) stent. The procedural success rate was 98%. Mean coronary stenosis was
      82+/-10% and decreased to 20+/-15% after PTCA. No major complication occurred.
      The guiding catheter was immediately removed in 95% of patients, despite
      heparinization. No patient required surgery or blood transfusion for vascular
      complications, and only 7 had minor local complications (3.5%). Sheathless
      angioplasty provides no technical difficulties and has the same safety and
      quality as conventional angioplasty using a sheath. Immediate removal of the
      guiding catheter, without keeping vascular access, has no deleterious effect,
      allows early mobilization, and may limit the risk of vascular complications.

PMID- 9535379
TI  - Angioscopic evaluation of thrombus removal by the POSSIS AngioJet thrombectomy
      catheter.
AB  - Coronary angioplasty in a thombotic vein graft is associated with a low success
      rate and a high risk of periprocedural complications. The aspiration thrombectomy
      catheter is a new device designed to treat such cases. We report a first
      angioscopic description of thrombus removal by the AngioJet thrombectomy
      catheter.

PMID- 9535380
TI  - New guiding catheter for transrad PTCA.
AB  - A new guiding catheter for PTCA is described. In our department, 302 patients
      (405 lesions) underwent transradial coronary angioplasty using the 6 Fr Kimny
      guiding catheter since January 1996. The total engagement rate using the Kimny
      guiding catheter was 91.3% (370/405). The engagement rate after the modified
      Kimny guiding catheter was introduced in May 1996 increased to 96.0% (243/253).
      The stent delivery success rate was 98.4%. We had two dislodged stents. PTCA for
      both left and right coronary arteries in a single procedure with the Kimny
      guiding catheter was performed via the radial artery in 27 patients. In 24 of
      these patients (89%) we engaged both coronaries successfully. In the remaining 3
      patients we switched to another catheter. Except for 4 patients with non-Q-wave
      myocardial infarction, no major cardiac complications were encountered. No major
      entry site-related complications were seen, and no patient required vascular
      surgery or blood transfusions. In one patient the Kimny guiding catheter tip
      caused a minor dissection of the LMT, but no ischemic event occurred as a result.
      In conclusion, the Kimny device is a useful PTCA guiding catheter for routine
      angioplasty and stenting.

PMID- 9535381
TI  - Novel long-neck sheath for endomyocardial biopsy.
AB  - We studied a novel-shaped long-neck sheath for endomyocardial biopsy through the
      internal jugular approach. The sheath is designed to provide a stable platform
      that facilitates direct atraumatic passage of the biopsy forceps in close
      proximity to and oriented toward the target septal site, which avoids undesirable
      repetitive recrossing of the right heart structures, thereby minimizing risk of
      cardiac trauma. This endomyocardial biopsy sheath was easy to advance and
      position in the heart and consistently provided a stable platform to deliver
      efficiently and safely the bioptome to the optimal target septal site. The use of
      this sheath has potential to reduce trauma to the patient, limit radiation
      exposure, and minimize procedure time.

PMID- 9535382
TI  - User-friendly and low-cost computer system for immediate review, analysis, and
      reconstruction of intracoronary ultrasound images.
AB  - Rapid review, digital recording, on-line quantification, and three-dimensional
      reconstruction are all essential in the evaluation of intracoronary ultrasound
      images during coronary interventions. We describe a low-cost method that offers
      all these necessary features. The proposed method uses the QuickTime compatible
      video digitizers of standard multimedia Apple Macintosh or PowerPC desktop
      computers and the freeware software Object Image 1.60.

PMID- 9535383
TI  - An ancestor to intervention.

PMID- 9535384
TI  - Accurate measurement of LIMA flow velocity.

PMID- 9535385
TI  - Impact of aortocoronary graft markers on subsequent graft patency: a
      retrospective review.

PMID- 9535386
TI  - Extrasupport guidewire as primary wire for percutaneous transluminal coronary
      angioplasty.

PMID- 9535387
TI  - Enterococci: susceptibility, resistance, and now dependence on vancomycin.

PMID- 9535388
TI  - The diagnostic accuracy of bedside and laboratory coagulation: procedures used to
      monitor the anticoagulation status of patients treated with heparin.
AB  - We evaluated the diagnostic accuracy of three bedside coagulation procedures, the
      Hemochron activated whole-blood clotting time (ACT) (International Technidyne,
      Edison, NJ), the CoaguChek Plus (Boehringer Mannheim, Indianapolis, Ind)
      activated partial thromboplastin time (APTT) and the TAS (Cardiovascular
      Diagnostics, Raleigh, NC) APTT, before removal of arterial sheaths, in patients
      who received heparin therapy during percutaneous coronary angioplasty. As part of
      the postprocedure care, nurses performed bedside coagulation tests, removed the
      sheaths when appropriate coagulation criteria were met, and collected samples for
      laboratory APTT determinations and heparin assays performed with an automated
      chromogenic anti-Xa assay. Patients with heparin concentrations of 0.3 U/mL or
      more were classified as anticoagulated and those with concentrations less than
      0.3 U/mL, as not anticoagulated. Analysis of the receiver operator characteristic
      (ROC) curve was used to rank the performance of the methods. Areas under the ROC
      curves +/- SE for the laboratory APTT, CoaguChek Plus APTT, Hemochron ACT, and
      TAS APTT were 0.978 +/- 0.016, 0.872 +/- 0.044, 0.797 +/- 0.039, and 0.795 +/-
      0.048, respectively. At cutoff values for the tests that provide greatest safety
      for the patients (no false-negative results), the false-positive rates for the
      laboratory, CoaguChek Plus, Hemochron, and TAS methods were 15%, 27%, 62%, and
      100%, respectively. The laboratory APTT demonstrated the highest diagnostic
      accuracy in this application; however, turnaround time for the test (50% of the
      results were reported in excess of 77 minutes) was inadequate for clinical
      decision making. To meet this requirement, we developed a point-of-care program
      using the whole blood APTT performed on the CoaguChek Plus analyzer.

PMID- 9535389
TI  - Coagulation parameters of ABO group-specific cryosupernatant.
AB  - Patients with thrombotic thrombocytopenic purpura that is refractory to
      conventional fresh frozen plasma (FFP) exchange therapy are sometimes switched to
      cryosupernatant as the replacement fluid, although its hemostatic properties are
      not well defined. We performed several key coagulation assays on three pools of
      four units from each of three ABO groups of cryosupernatant and FFP. Fibrinogen,
      factor VIII activity, and von Willebrand factor antigen (vWF:Ag) levels were all
      significantly lower in cryosupernatant compared with FFP, although at levels
      usually not considered clinically significant. We confirmed that group O FFP
      contained significantly less factor VIII activity and vWF:Ag compared with groups
      AB and B. In contrast to FFP, group AB cryosupernatant contained lower levels of
      fibrinogen, factor V activity, factor VIII activity, and vWF:Ag than groups O or
      B. Group AB cryosupernatant, with the lowest levels of vWF:Ag and universal ABO
      compatibility, may be the product of choice for refractory thrombotic
      thrombocytopenic purpura.

PMID- 9535390
TI  - Whole blood screening test for factor V Leiden using a Russell viper venom time
      based assay.
AB  - Factor V Leiden (FVR506Q) is a genetic defect in the factor V (FV) molecule that
      confers resistance to proteolysis by activated protein C (APC) and is the most
      common abnormality detected in patients studied for hereditary thrombophilia. The
      initial screening test for this abnormality was a comparison of the activated
      partial thromboplastin time (APTT) in the presence and absence of APC, expressed
      as a ratio. But this has been shown to lack sensitivity for the FV mutation.
      Other clot-based screening tests, such as the modified APTT, using FV-deficient
      plasma, or the Russell viper venom (RVV) time assay have improved sensitivity.
      Eighty-seven samples were studied using the RVV-based assay. This assay was
      performed on platelet-poor plasma (PPP-RVV) and whole blood (WB-RVV). All samples
      were analyzed by polymerase chain reaction (PCR) for the FV Leiden defect: 77
      were PCR negative; 10 were PCR positive. Using a threshold ratio of 1.8, all
      samples were correctly categorized in the PPP-RVV and the WB-RVV tests, showing
      an observed sensitivity and specificity of 1.0. These results suggest that an RVV
      based assay using whole blood could be an effective screening test for this
      common abnormality.

PMID- 9535392
TI  - Antimicrobial susceptibility testing of a clinical isolate of vancomycin
      dependent enterococcus using D-alanine-D-alanine as a growth supplement.
AB  - Bacteremia due to a vancomycin-dependent enterococcus (VDE) occurred during long
      term vancomycin therapy in a renal transplant recipient with underlying
      pancreatitis and a vancomycin-resistant enterococcal (VRE) wound infection and
      bacteremia. The VDE was isolated from blood during vancomycin therapy and grew
      only in the presence of vancomycin and D-alanine-D-alanine (DADA), a substance
      required for cell-wall synthesis. Colonies beyond the periphery of growth of the
      VDE around a vancomycin disk contained vancomycin-independent revertant mutants
      after 48 hours of incubation. Pulsed-field gel electrophoresis of the VDE,
      revertant mutant, the initial blood culture isolate of VRE, and an autopsy
      isolate showed that the four strains were identical. Antimicrobial susceptibility
      testing was performed using standard macrobroth and microbroth dilution methods.
      DADA was used as a growth supplement for macrobroth dilution susceptibility
      testing of the VDE isolate. Minimum inhibitory concentrations (MICs) were similar
      for the VRE isolate and the VDE revertant, which were both resistant to
      ampicillin, high-level gentamicin, ciprofloxacin, imipenem, vancomycin, and
      daptomycin, and were susceptible to fusidic acid, high-level streptomycin,
      rifampin, and a quinupristin-dalfopristin combination. The MICs of teicoplanin
      were 2 microg/mL or less and 16 microg/mL for the clinical VRE isolate and the
      VDE revertant, respectively. The autopsy isolate was resistant to all
      antimicrobials tested and showed a fourfold increase in MICs for quinupristin
      dalfopristin compared with that of the original blood isolate. The VDE was
      susceptible to all drugs tested except vancomycin.

PMID- 9535391
TI  - Collagen-induced whole blood platelet aggregation in patients undergoing surgical
      procedures associated with minimal to moderate blood loss.
AB  - Intraoperative bleeding due to platelet disorders is a persistent problem.
      Therefore, a screening assay to identify patients who are likely to bleed as a
      result of platelet dysfunction would be useful in formulating decisions about
      patient care. A previous study indicated that preoperative collagen-induced whole
      blood platelet aggregation predicts bleeding in patients undergoing surgery with
      cardiopulmonary bypass, a procedure associated with substantial blood loss. In
      the current study, we assessed the ability of the same whole blood platelet
      aggregation test to predict blood loss in patients undergoing surgical procedures
      not associated with substantial blood loss. The study included 369 adult patients
      (165 men and 204 women). Patients were categorized in three groups depending on
      the invasiveness of the operation and the expected blood loss. The intraoperative
      estimated blood loss value, obtained from the operative report in the patient
      record, increased significantly with increasing surgical invasiveness. Patients
      with excessive blood loss (defined as blood loss at or above the 75th or 90th
      percentile of the estimated blood loss values of patients undergoing procedures
      of similar invasiveness) had similar platelet aggregation values as patients who
      did not experience excessive blood loss. Thus, for patients undergoing operations
      not associated with substantial blood loss, the results of preoperative collagen
      induced whole blood platelet aggregation are not effective in identifying
      patients likely to experience excessive blood loss.

PMID- 9535393
TI  - Optimal screening and diagnosis of microsporida in tissue sections: a comparison
      of polarization, special stains, and molecular techniques.
AB  - With improving therapeutic protocols, confirmation of microsporidiosis has become
      increasingly important. We designed a study to determine the best screening
      method(s) for microsporidian detection in biopsy specimens. Forty-two small
      intestinal biopsy specimens from 31 immunocompromised patients (68% AIDS) were
      stained (hematoxylin-eosin [H & E], modified trichrome, Warthin-Starry, and Brown
      Brenn) and polarized. Polymerase chain reaction and Southern blot assays were
      performed on all positive cases. Microsporida were detected in nine cases (21%)
      by modified trichrome (all patients with AIDS). Of these, seven were Brown-Brenn
      positive, and five Warthin-Starry positive. Two cases polarized on H & E and
      three on special stains. Four of nine positive cases were confirmed by molecular
      studies. We found polarization to be the least sensitive screening method. The
      modified trichrome was the most sensitive when screening for microsporidiosis in
      paraffin-embedded biopsy specimens. Furthermore, combining Brown-Brenn or Warthin
      Starry with the trichrome stain helps exclude false-positive results due to
      granular artifacts (eg, eosinophils, Paneth cells).

PMID- 9535395
TI  - Diagnostic effect of complete histologic sampling of prostate needle biopsy
      specimens.
AB  - In 1997, approximately 1 million 18-gauge prostate needle core biopsies were
      performed in the United States. Yet limited data exist on the effect of
      histologic sampling on detection of carcinoma in needle biopsy tissue, and no
      data have been published on the diagnostic yield of complete histopathologic
      examination of prostate needle biopsy specimens. We sought to evaluate the
      diagnostic effect of obtaining additional sections after a nonmalignant diagnosis
      was given on three initial slides. This prospective study was of 200
      consecutively identified cases. Complete histologic examination of all needle
      biopsy tissue from 100 cases diagnosed as atypia (encompassing high-grade
      prostatic intraepithelial neoplasia [PIN] and focal glandular atypia) on the
      initial three slides was compared with complete examination for a control
      population of 100 cases diagnosed as benign prostatic tissue on the initial three
      slides. New histologic abnormalities in levels were characterized as to
      diagnostic category, distribution in additional slides and morphometrically
      determined size. Complete histologic sampling of prostate needle biopsy specimens
      with serial sections entirely through the paraffin block required a mean of 30
      slides per block, with a mean of 4 sections per slide. In 17 (17%) cases with
      atypia diagnosed on the initial three slides, a new histologic abnormality was
      detected in levels. In 4 (10%) of 40 cases of focal glandular atypia, definitive
      carcinoma was present on additional sections, including the first additional
      slide. In no case with a diagnosis of benign prostatic tissue (n = 100) or high
      grade PIN (n = 60) on the three initial slides was carcinoma diagnosed on
      additional slides. Additional histologic sampling after a diagnosis of isolated
      high-grade PIN does not seem necessary; these patients with high-grade PIN should
      undergo rebiopsy. Because of the profound consequences of a definitive diagnosis
      of prostatic carcinoma, we recommend obtaining a single additional slide with
      several 3-microm sections after a diagnosis of focal glandular atypia has been
      given for three initial slides of needle biopsy specimens from the prostate.

PMID- 9535394
TI  - Nested polymerase chain reaction for Mycobacterium tuberculosis IS6110 sequence
      on formalin-fixed paraffin-embedded tissues with granulomatous diseases for rapid
      diagnosis of tuberculosis.
AB  - We evaluated the sensitivity and specificity of a nested polymerase chain
      reaction (PCR) to the Mycobacterium tuberculosis IS6110 sequence on formalin
      fixed paraffin-embedded tissue samples from patients with tubercular and other
      granulomatous lesions. Five groups of patients and samples were studied: (1) 28
      samples from HIV-positive patients with tuberculosis, (2) 8 samples from HIV
      negative patients with histologically suspected tuberculosis (confirmed by
      culture in 5 cases), (3) lymph nodes from 5 HIV-positive patients with
      Mycobacterium avium-intracellulare infection, (4) lymph nodes from 30 patients
      with sarcoidosis, and (5) specimens from 17 patients with other granulomatous
      diseases. The DNA was extracted from sections with a total thickness of 60
      microm, and PCR amplified an internal fragment of 123 base pairs. All of the
      cases with M. tuberculosis infection were PCR-positive, although this sensitivity
      was partially related to the initial concentration of the DNA used for
      amplification. Two of the group 4 samples also were repeatedly positive, thus
      reducing the specificity of the method. All of the cases with granulomatous
      diseases other than sarcoidosis were negative. We propose a simplified and highly
      sensitive nested PCR for the diagnosis of M. tuberculosis infection on archived
      material in HIV-positive and HIV-negative patients.

PMID- 9535396
TI  - Mucinous bronchioloalveolar carcinoma with organoid differentiation simulating
      the pyloric mucosa of the stomach: clinicopathologic, histochemical, and
      immunohistochemical analysis.
AB  - Seven cases of mucus-producing bronchioloalveolar carcinoma, which showed
      organoid differentiation simulating the gastric pyloric mucosa, were found among
      176 cases of lung cancer. This type of adenocarcinoma, which corresponds to
      bronchioloalveolar carcinoma with mucus-secreting cells in the World Health
      Organization classification, characteristically formed papillary structures
      composed of two types of mucus cells: tall columnar cells in the upper portion of
      the papillary structure and more cuboidal cells in the lower portion. The former
      contained gastric surface mucous cell-type mucins that stained with galactose
      oxidase-cold thionine Schiff, whereas the latter possessed gastric gland mucous
      cell-type mucins specifically stained by paradoxical concanavalin A and were also
      positive for lysozyme and pepsinogen II by immunostaining. Chromogranin A
      reactive tumor cells were also scattered among these tumor cells. This pattern of
      mucus-secreting cells, therefore, simulated the normal pyloric mucosa of the
      stomach.

PMID- 9535397
TI  - Reduced E-cadherin immunohistochemical expression in node-negative breast
      carcinomas correlates with 10-year survival.
AB  - E-cadherin immunodetection was performed on frozen sections, using an
      immunoperoxidase procedure and with computer-assisted analysis of digitized
      colored microscopic images in a series of 179 breast carcinomas. Quantitative
      immunocytochemical assays were correlated with follow-up (129 months). The
      results showed that reduced E-cadherin immunocytochemical expression in tumors
      (cut point, 4%) significantly correlated with shorter overall survival in node
      negative patients (Kaplan Meier log rank test). But E-cadherin immunostained
      expression (cut point, 4%) did not correlate with metastasis-free or recurrence
      free survival. In multivariate analysis (Cox proportional hazards regression
      model), E-cadherin prognostic significance for overall survival in node-negative
      patients was independent of the tumor size, grade, and histologic type. The
      results suggest that reduced E-cadherin expression detected in optimum technical
      conditions (frozen samples and quantitative immunohistochemistry) is an
      independent indicator of poor survival in node-negative patients and may be
      clinically relevant for the treatment of patients with breast carcinomas.

PMID- 9535398
TI  - Fine-needle aspiration of gastrointestinal stromal tumors.
AB  - Gastrointestinal stromal tumors are a group of neoplasms encompassing leiomyoma,
      leiomyosarcoma, and an epithelioid variant of leiomyosarcoma, as well as lesions
      expressing neural differentiation. These neoplasms are rare and account for 1% of
      all gastrointestinal tumors. With increasing frequency, fine-needle aspiration
      (FNA) has been used to diagnose intra-abdominal neoplasms before institution of
      definitive treatment. We encountered four patients with gastrointestinal stromal
      tumors diagnosed by FNA who ultimately underwent surgical excision of their
      tumors. The age of the patients ranged from 57 to 88 years. Smears from the
      aspirates were cellular and consisted of numerous small spindle cells distributed
      as cohesive fragments and individual cells. The dispersed cell population
      appeared largely as stripped nuclei. Several nuclei had perinuclear or
      paranuclear vacuoles, similar to the "halos" seen in sections. Cytologic evidence
      of malignancy (pleomorphism, nuclear irregularity, mitoses) were not identified
      in smears. Corresponding histologic sections demonstrated varying degrees of
      malignancy ranging from benign or low grade to frankly sarcomatous
      gastrointestinal stromal tumors. We conclude that the diagnosis of
      gastrointestinal stromal tumors can be made with a certain degree of confidence
      by using FNA findings. However, predictions about potential aggressiveness are
      best reserved for gross and histologic examination of the resected specimen.

PMID- 9535399
TI  - Gene therapy: ovarian carcinoma as the paradigm.
AB  - The delineation of the molecular basis of cancer in general, and of ovarian
      carcinoma in particular, allows for the possibility of specific intervention at
      the molecular level for therapeutic purposes. To this end, three main approaches
      have been developed: mutation compensation, molecular chemotherapy, and genetic
      immunopotentiation. For each of these conceptual approaches, human clinical
      protocols, including those specific for ovarian carcinoma, have entered phase I
      clinical trials to assess dose escalation, safety, and toxicity issues. However,
      major problems remain to be solved before these approaches can become effective
      and commonplace strategies for the treatment of cancer. In this regard, an
      examination of the applications of gene therapy for ovarian carcinoma can
      exemplify the rationality and the problems observed in the development of gene
      therapy, and may illustrate prospects for their solution that are being refined,
      including current efforts in our laboratory. An overriding obstacle is the basic
      ability to deliver therapeutic genes quantitatively, and specifically, into tumor
      cells. As vector technology fulfills these requirements, it is anticipated that
      promising results already observed in preclinical studies will translate quickly
      into the clinical setting for amelioration of this life-threatening disease in
      women.

PMID- 9535400
TI  - Specimen adequacy in FNAB of the breast.

PMID- 9535401
TI  - CD16 expression in chronic myeloid leukemia.

PMID- 9535402
TI  - Critical values, panic values, or alert values?

PMID- 9535403
TI  - Social support in persons with self-reported sensitivity to chemicals.
AB  - Social support was examined in 305 persons with multiple chemical sensitivity
      using the Personal Resource Questionnaire 85 (PRQ85; Weinert, 1987) and
      qualitative descriptions of respondents' social interactions. PRQ85 scores were
      lower than those of healthy populations, but similar to samples with chronic
      illness. Participants needed but were prevented from receiving support for
      personal difficulties due to their limited public access, their need for chemical
      avoidance including fragrances, and others' lack of information and negative
      attitudes regarding chemical sensitivities. Respondents drew some support and
      validation from support groups and from romantic relationships. Fatigue level,
      being in a romantic relationship, contact with a support group on a monthly or
      more frequent basis, chemical avoidance in the home, gender, and an improved
      course of illness predicted 19% of the variance for perceived social support.
      Qualitative data are used to illustrate particular problems of persons in this
      sample, and suggestions are made for practitioners who encounter this population.

PMID- 9535404
TI  - Relationship of social support to stress responses and immune function in healthy
      and asthmatic adolescents.
AB  - Although most clinicians believe that social support has beneficial effects on
      health, the mechanisms mediating this relationship have not been clearly
      established. We examined the direct effect of social support on several immune
      measures and its role in moderating the response to academic exams in healthy and
      asthmatic adolescents. Three types of students--healthy, mild asthma, and severe
      asthma--completed social support and stress questionnaires and gave blood samples
      during the midsemester and final exam periods. Social support and natural killer
      cell (NK) function showed a significant reduction during exams in both healthy
      and asthmatic adolescents. Social support, however, did not have a direct effect
      on immune responses. Nevertheless, high social support appeared to attenuate the
      magnitude of exam-induced reduction in NK activity, suggesting a role for social
      support in protecting against immune decrements during times of stress.

PMID- 9535405
TI  - Luteal phase ovarian steroids, stress arousal, premenses perceived stress, and
      premenstrual symptoms.
AB  - The purpose of this study was to examine the relationships among perceived
      stress, ovarian steroids (estradiol and pregnanediol), stress arousal indicators
      (cortisol, catecholamines) and premenstrual symptoms (turmoil, fluid retention).
      Women (N = 74) with low symptom severity (LS), premenstrual syndrome (PMS), or
      premenstrual magnification (PMM) symptom patterns provided daily urine samples
      over one cycle and recorded their symptoms and perceived stress levels in a
      health diary. Multiple regression analysis was used to test models of
      premenstrual symptoms in separate analyses for women with the LS and PMS symptom
      patterns and the LS and PMM symptom patterns. Data from the LS and PMS groups
      revealed that greater stress ratings accounted for turmoil symptoms and higher
      luteal phase cortisol levels for fluid retention symptoms. For LS and PMM groups,
      lower luteal phase norepinephrine levels, higher global stress ratings, and a
      more gradual drop in estradiol premenses accounted for turmoil symptoms.
      Premenses norepinephrine and epinephrine levels and premenses stress ratings
      accounted for fluid retention. These findings support an important relationship
      among perceived stress, stress arousal indicators, and premenstrual symptoms that
      differs for women with a PMS and PMM symptom pattern.

PMID- 9535406
TI  - Patterns of spirituality in persons with advanced HIV disease.
AB  - This study was conducted to explicate the role of spirituality in dealing with
      the many struggles of advanced HIV disease. The research question that guided the
      study was: How is spiritual meaning structured in advanced stages of HIV disease?
      Published articles have lacked sound conceptions of spirituality that would allow
      it to be described apart from religion as a concept within humanistic science.
      Qualitative methodological assumptions were derived from interpretive
      interactionism. The spiritual experiences of 10 men and women in advanced-stage
      (symptomatic) HIV disease who self-identified that they had either spiritual or
      religious experiences that had helped them cope with HIV disease were
      interpreted. Data were collapsed, over three iterations, into three major themes
      to build the meaning of spirituality in HIV. Extracted themes were: purpose in
      life emerges from stigmatization; opportunities for meaning arise from a disease
      without a cure; and after suffering, spirituality frames the life.

PMID- 9535407
TI  - Psychosocial adjustment to breast cancer in unmarried women.
AB  - Breast cancer is a significant health problem that can affect many aspects of a
      woman's life. Although there is growing evidence that women with supportive
      husbands seem to adjust reasonably well, little is known about the impact of
      breast cancer among unmarried women. Relationships among primary treatment
      alternatives, symptom distress, perceived social support, and psychosocial
      adjustment to breast cancer in 101 unmarried women were investigated using data
      collected during the late postoperative recovery phase. The women experienced
      relatively low levels of psychosocial adjustment problems and perceived
      moderately high levels of social support. Social support and symptom distress
      each accounted for significant proportions of the variance in psychosocial
      adjustment, whereas primary treatment alternatives did not. Symptom distress
      emerged as the variable accounting for the most variance in psychosocial
      adjustment to breast cancer. Implications for health care providers to facilitate
      positive adjustment to breast cancer in unmarried women and directions for future
      studies are suggested.

PMID- 9535408
TI  - The history and future of nursing labor research in a cost-control environment.
AB  - For the first time in nursing's history, the downsizing of hospitals, the
      increased use of managed care, reduced use of registered nurses and other factors
      may result in significant unemployment in nursing, with resulting downward
      adjustments in the wage. Understanding the labor supply response of nurses to
      changes in the wage is critical to predicting accurately how nurses will respond
      to changes in the market demand as it influences wages, and determining rational
      policy responses to the labor market. In this article, three generations of
      nursing labor research are summarized and critiqued. Methodological issues are
      discussed and specific directions for future studies are suggested.

PMID- 9535409
TI  - Ready-to-wear: discovering grounded formal theory.
AB  - As qualitative methods have become popular and qualitative reports abundant,
      researchers have begun to discuss techniques for synthesizing findings about
      related phenomena from diverse samples. Grounded formal theory analysis is one
      such approach that can yield higher level, broadly applicable theory from
      analysis of situation-specific substantive theories. Although grounded formal
      theories may lack the cultural detail and contextual tailoring of smaller, more
      focused "designer" analyses, they have the potential to serve as "ready-to-wear"
      models that fit experiences of individuals in a variety of settings.

PMID- 9535411
TI  - Gender-specific association of M235T polymorphism in angiotensinogen gene and
      diabetic nephropathy in NIDDM.
AB  - This study examined the association between the development of nephropathy in non
      insulin-dependent diabetes mellitus (NIDDM) patients and M235T polymorphism in
      the angiotensinogen gene. White NIDDM patients with diabetic nephropathy (case
      subjects, n = 117) and patients without any evidence of nephropathy and > or = 10
      years of NIDDM (control subjects, n = 125) were selected from among patients of
      the Joslin Diabetes Center and examined. In addition to a standardized
      examination, blood was drawn for DNA and determination of M235T genotypes at the
      angiotensinogen locus. For the angiotensinogen gene, the frequency of the
      genotype 235T/235T, known to be associated with essential hypertension, was
      higher among case subjects with nephropathy than in control subjects without this
      complication. This difference, expressed as the odds ratio for nephropathy among
      235T/235T homozygotes in comparison with all other genotypes, was 2.2 (95%
      confidence interval, 1.1 to 4.4). The difference, however, was confined to men
      (odds ratio, 4.8; 95% confidence interval, 1.5 to 14.9), with the distribution of
      genotypes in case and control subjects being equal among women (odds ratio, 1.1).
      DNA polymorphism M235T in the angiotensinogen gene, which is associated with
      higher expression of this gene, contributes to the risk of diabetic nephropathy
      in NIDDM men but not in women.

PMID- 9535410
TI  - Increased glucocorticoid activity in men with cardiovascular risk factors.
AB  - The association between hypertension and insulin resistance might be explained by
      increased activity of the principal glucocorticoid, cortisol. Recent data show
      that the intensity of dermal vasoconstriction after topical application of
      glucocorticoids is increased in patients with essential hypertension. In this
      report, we examine whether increased glucocorticoid sensitivity or secretion is
      associated with insulin resistance and is a cause or consequence of hypertension.
      We studied 32 men (aged 47 to 56 years) from a cross-sectional study and 105 men
      (aged 23 to 33 years) in whom predisposition to high blood pressure has been
      defined by their own blood pressure and the blood pressures of their parents. In
      both populations, increased dermal glucocorticoid sensitivity was associated with
      relative hypertension, insulin resistance, and hyperglycemia. In young men with
      higher blood pressure whose parents also had high blood pressure, enhanced
      glucocorticoid sensitivity was accompanied by enhanced secretion of cortisol,
      enhanced ligand-binding affinities for dexamethasone in leukocytes, and impaired
      conversion of cortisol to inactive metabolites (cortisone and 5beta
      dihydrocortisol). Increased tissue sensitivity to cortisol, amplified by enhanced
      secretion of cortisol, is a feature of the familial predisposition to high blood
      pressure rather than a secondary effect of high blood pressure. It may be
      mediated by an abnormal glucocorticoid receptor, and it may contribute to the
      association between hypertension and insulin resistance.

PMID- 9535412
TI  - Angiotensin-converting enzyme gene polymorphism is associated with endothelium
      dependent vasodilation in never treated hypertensive patients.
AB  - The response of the forearm vasculature to acetylcholine (7.5, 15, and 30
      microg/min, each for 5 minutes) and sodium nitroprusside (0.8, 1.6, and 3.2
      microg/min, each for 5 minutes) was evaluated in 32 never-treated hypertensive
      outpatients (17 men and 15 women, aged 43+/-7 years) and in 24 normotensive
      control subjects (14 men and 10 women, aged 42+/-6 years). Drugs were infused
      into the brachial artery, and forearm blood flow was measured by strain-gauge
      plethysmography. In both hypertensive and normotensive groups, a deletion
      (D)/insertion (I) polymorphism in intron 16 of the angiotensin-converting enzyme
      (ACE) gene was determined by polymerase chain reaction. The response to
      acetylcholine was significantly reduced in hypertensive patients versus control
      subjects: at the highest dose (30 microg/min), forearm blood flow was 13.9+/-6.3
      mL x 100 mL tissue(-1) x min(-1) in hypertensives versus 27.1+/-9.7 mL x 100 mL
      tissue(-1) x min(-1) in the controls (P<.001); similarly, vascular resistance was
      10.6+/-5.6 U in hypertensive patients and 4.9+/-1.9 U in normotensive subjects.
      In the hypertensive group, the patients with DD genotype showed significantly
      less endothelium-dependent vasodilation compared with ID+II genotypes (at the
      highest dose of acetylcholine, forearm blood flow was 12.1+/-4.2 versus 17.0+/
      4.1 mL x 100 mL tissue(-1) x min(-1)) (P<.005). The vasodilator effect of sodium
      nitroprusside infusions was not statistically different in DD and ID+II
      hypertensive patients. In conclusion, our data suggest that ACE polymorphism
      affects endothelium-dependent vasodilation in hypertensive patients and confirm
      that hypertensive patients had a blunted response to the endothelium-dependent
      agent acetylcholine.

PMID- 9535413
TI  - Identification of human plasma kallikrein gene polymorphisms and evaluation of
      their role in end-stage renal disease.
AB  - Kallikreins are serine proteases that release kinins from kininogens. Kinins, via
      their effects on cardiovascular and renal function, may be involved in the
      pathogenesis of hypertension and renal failure. Two groups of kallikreins exist,
      glandular or tissue kallikrein and plasma kallikrein. In this study, we examined
      the human plasma kallikrein gene KLK3 to determine whether it contributed to end
      stage renal disease (ESRD) susceptibility. We identified two novel polymorphic
      sequences closely linked to the KLK3 gene, designated KLK3b and KLK3c
      (heterozygosities: 0.64 to 0.68 and 0.48 to 0.52, respectively). We mapped the
      KLK3 gene and the marker KLK3c to the long arm of human chromosome 4 between F11
      and D4S426 using a radiation hybrid panel. The study population consisted of 142
      sibling pairs concordant for ESRD from 121 African American families. The 142
      sibling pairs were stratified into 78 pairs with hypertension- and chronic
      glomerulonephritis-associated ESRD and 64 with non-insulin-dependent diabetes
      mellitus-associated ESRD. Linkage analyses, using SIBPAL of SAGE, and exclusion
      analysis, using MAPMAKERS/SIBS, were performed. Linkage analysis of affected
      sibling pairs did not reveal any evidence of linkage of KLK3 to ESRD in all 142
      sib-pairs or in the two stratified subsets. Exclusion analysis indicated that the
      KLK3 gene could be excluded from contributing to ESRD at a relative risk of 3
      when the maximum log of the odds score of -2 was used as the criterion for
      exclusion. However, an association analysis using the relative predispositional
      effect technique showed that alleles 7 and 9 of KLK3b were consistently
      associated with ESRD. Alleles 7 and 9 were present in 11.2% and 10.8% of the 113
      unrelated ESRD probands and in 6.6% and 6.6% of the 204 race-matched control
      subjects without renal disease (allele P=.0041 and .0016, respectively). Alleles
      7 and 9 were also present in 13% and 10.4% of the proband's first siblings
      (allele P=.00014 and .0087, respectively). The association of KLK3b alleles with
      ESRD raises the possibility that polymorphisms in KLK3 may play a role in ESRD
      susceptibility. The lack of linkage might reflect our relatively small family
      set.

PMID- 9535414
TI  - N-domain-specific substrate and C-domain inhibitors of angiotensin-converting
      enzyme: angiotensin-(1-7) and keto-ACE.
AB  - We used the isolated N- and C-domains of the angiotensin 1-converting enzyme (N
      ACE and C-ACE; ACE; kininase II) to investigate the hydrolysis of the active 1-7
      derivative of angiotensin (Ang) II and inhibition by 5-S-5-benzamido-4-oxo-6
      phenylhexanoyl-L-proline (keto-ACE). Ang-(1-7) is both a substrate and an
      inhibitor; it is cleaved by N-ACE at approximately one half the rate of
      bradykinin but negligibly by C-ACE. It inhibits C-ACE, however, at an order of
      magnitude lower concentration than N-ACE; the IC50 of C-ACE with 100 micromol/L
      Ang I substrate was 1.2 micromol/L and the Ki was 0.13. While searching for a
      specific inhibitor of a single active site of ACE, we found that keto-ACE
      inhibited bradykinin and Ang I hydrolysis by C-ACE in approximately a 38- to 47
      times lower concentration than by N-ACE; IC50 values with C-ACE were 0.5 and 0.04
      micromol/L. Furthermore, we investigated how Ang-(1-7) acts via bradykinin and
      the involvement of its B2 receptor. Ang-(1-7) was ineffective directly on the
      human bradykinin B2 receptor transfected and expressed in Chinese hamster ovary
      cells. However, Ang-(1-7) potentiated arachidonic acid release by an ACE
      resistant bradykinin analogue (1 micromol/L), acting on the B2 receptor when the
      cells were cotransfected with cDNAs of both B2 receptor and ACE and the proteins
      were expressed on the plasma membrane of Chinese hamster ovary cells. Thus like
      other ACE inhibitors, Ang-(1-7) can potentiate the actions of a ligand of the B2
      receptor indirectly by binding to the active site of ACE and independent of
      blocking ligand hydrolysis. This potentiation of kinins at the receptor level can
      explain some of the well-documented kininlike actions of Ang-(1-7).

PMID- 9535415
TI  - Vascular smooth muscle nitric oxide synthase anomalies in Dahl/Rapp salt
      sensitive rats.
AB  - Salt-sensitive hypertension in the Dahl/Rapp rat (S strain) is prevented by L
      arginine. Based on the observations that dexamethasone prevented the
      antihypertensive effect of L-arginine in these animals and the suggestion that a
      locus in or near an inducible nitric oxide synthase (NOS) gene on chromosome 10
      cosegregated with hypertension in some F2 crosses that utilized the S rat, the
      present study explored the hypothesis that the vascular smooth muscle isoform of
      inducible NOS (NOS2) was abnormal in S rats. Primary cultures of aortic smooth
      muscle cells from S rats demonstrated impaired inducible NO production, which
      improved with increased L-arginine in the medium. Sequence analysis identified a
      single T-->C transversion that produced an amino acid substitution (S714P)
      between the FAD and FMN binding sites and a restriction fragment length
      polymorphism. This restriction fragment length polymorphism was present only in S
      rats. The mutation of NOS2 and the role of this enzyme in the pathogenesis of
      salt-sensitive hypertension in the Dahl/Rapp rat require further investigation.

PMID- 9535416
TI  - Three candidate genes and angiotensin-converting enzyme inhibitor-related cough:
      a pharmacogenetic analysis.
AB  - Unexplained, persistent cough limits the use of angiotensin-converting enzyme
      (ACE) inhibitors in a significant number of patients. It has been speculated that
      occurrence of this adverse effect is genetically predetermined; in particular,
      variants of the genes encoding ACE, chymase, and B2-bradykinin receptor have been
      implicated. To investigate this question, we determined genotypes for common
      polymorphisms for these three genes in subjects with a history of ACE inhibitor
      related cough. Specificity of the adverse effect was confirmed by a blinded,
      double-crossover design protocol in which subjects were rechallenged with either
      lisinopril or placebo. In 99 case subjects and 70 control subjects (who failed to
      develop cough on rechallenge with ACE inhibitor) thus selected, frequencies for
      the ACE D and I alleles were 0.56 and 0.44 (cases) and 0.56 and 0.44 (controls),
      respectively; frequencies for chymase A and B alleles (absence/presence of BstXI
      site) were 0.56 and 0.44 (cases) and 0.46 and 0.54 (controls), respectively;
      frequencies for B2-bradykinin receptor + and - alleles (presence/absence of a 21
      to 29 nonanucleotide sequence) were 0.52 and 0.48 (cases) and 0.53 and 0.47
      (controls), respectively. All observed genotype frequencies were in Hardy
      Weinberg equilibrium. There was no evidence for association between genotype at
      either gene examined and cough (adjusted for gender and age). Our data indicate
      that common genetic variants of ACE, chymase, and B2-bradykinin receptor do not
      explain the occurrence of ACE inhibitor-related cough.

PMID- 9535417
TI  - Relation of left ventricular midwall function to cardiovascular risk factors and
      arterial structure and function.
AB  - Left ventricular (LV) midwall shortening (MWS) is subnormal in relation to LV
      circumferential end-systolic stress (ESS) (ESS-corrected MWS) in many
      hypertensive patients with normal LV chamber function and predicts subsequent
      morbidity and mortality. However, little is known of the relations of LV midwall
      function to demographic and metabolic variables or to arterial geometry.
      Asymptomatic, unmedicated normotensive (n=366) or hypertensive (n=282) adults
      were assessed with echocardiography and carotid ultrasound. In normal adults,
      lower LV MWS and ESS-corrected MWS, an index of LV contractility, were related
      independently to high total peripheral resistance, high heart rate, and male
      gender (all P<.00001), lower serum HDL cholesterol (P=.001) and diastolic
      pressure (P=.003), and for ESS-corrected MWS only, arterial relative wall
      thickness (RWT, P=.03). Among hypertensive patients, lower values for both
      midwall function indices were associated independently with higher peripheral
      resistance (P<.00001), heart rate (P<.00005), body mass index (P<.01), and
      arterial RWT (P=.04), as well as male gender (P<.0002). In the entire population,
      lower LV MWS was independently related to higher peripheral resistance, heart
      rate (both P<.00001), body mass index (P=.0006) and arterial RWT (P=.009); male
      gender (P<.00001); and lower age (P=.004), diastolic pressure (P=.042), and
      systolic carotid artery expansion (P=.032). Lower ESS-corrected MWS in the entire
      population was independently associated with higher peripheral resistance and
      heart rate (both P<.00001), body mass index (P=.0006), arterial RWT (P=.004);
      male gender; and lower diastolic pressure (both P<.00001), age (P<.00005),
      arterial expansion in systole (P=.006), and serum HDL cholesterol levels (P=.04).
      Among a subset (n=60), ESS-corrected MWS was positively related to apolipoprotein
      A1 (P=.004) and negatively to hemoglobin A1c (P<.01). Thus, higher LV midwall
      function is associated with female gender and more favorable profiles of
      hemodynamics, metabolic pattern, and arterial structure and function.

PMID- 9535418
TI  - Time-voltage QRS area of the 12-lead electrocardiogram: detection of left
      ventricular hypertrophy.
AB  - Identification of left ventricular hypertrophy (LVH) using 12-lead ECG criteria
      based primarily on QRS amplitudes has been limited by poor sensitivity at
      acceptable levels of specificity. Because the product of QRS voltage and
      duration, as an approximation of the time-voltage area of the QRS complex, can
      improve accuracy of the 12-lead ECG for LVH, we examined the diagnostic value of
      true time-voltage area measurements of QRS complexes from the standard 12-lead
      ECG. Standard 12-lead ECGs and echocardiograms were obtained in 175 control
      subjects without LVH and in 74 patients with regurgitant valvular heart disease
      and LVH defined by echocardiographic criteria (indexed LV mass >110 g/m2 in women
      and >125 g/m2 in men). Standard voltage criteria, voltage-duration products
      (voltage multiplied by QRS duration), and true time-voltage areas of the QRS were
      calculated for Sokolow-Lyon criteria (SV1 +RV(5/6)) and the 12-lead sum of
      voltage criteria. Test sensitivities were compared using gender-specific
      partitions with matched specificity of 98% in the 175 subjects without LVH.
      Measurement of the time-voltage area significantly improved sensitivity for both
      criteria. The 76% sensitivity of the 12-lead sum area and 65% sensitivity of
      Sokolow-Lyon area were significantly greater than the 54% sensitivity of the
      approximation of QRS area provided by each voltage-duration product (P<.001 and
      P=.021) and than the 46% and 43% sensitivities of the respective simple voltage
      criteria (each P<.001). Comparison of receiver operating characteristic curves
      confirmed the superior overall performance of time-voltage area criteria compared
      with both voltage-duration products and simple voltage criteria. These results
      suggest that use of time-voltage areas can dramatically improve identification of
      LVH by 12-lead ECG. Further study of this approach is needed to identify optimal
      criteria for LVH based on the time-voltage area measurements from the 12-lead
      ECG.

PMID- 9535419
TI  - Adenosine inhibits collagen and protein synthesis in cardiac fibroblasts: role of
      A2B receptors.
AB  - The objective of this study was to characterize the effects of exogenous and
      endogenous (cardiac fibroblast-derived) adenosine on [3H]proline and [3H]leucine
      incorporation, which are reliable markers of collagen and total protein
      synthesis, respectively, in rat left ventricular cardiac fibroblasts. Growth
      arrested confluent cardiac fibroblast monolayers were stimulated with 2.5% fetal
      calf serum (FCS) in the presence and absence of adenosine, 2-chloroadenosine
      (stable adenosine analogue), or modulators of adenosine levels including (1)
      erythro-9-(2-hydroxy-3-nonyl) adenine (adenosine deaminase inhibitor), (2)
      dipyridamole (adenosine transport blocker), and (3) iodotubericidin (adenosine
      kinase inhibitor). All agents inhibited in a concentration-dependent fashion FCS
      induced [3H]proline and [3H]leucine incorporation. These effects were blocked by
      KF17837 (selective A2 antagonist) and 1,3-dipropyl-8-(p-sulfophenyl)xanthine
      (A1/A2 receptor antagonist) but not by 8-cyclopentyl-1,3-dipropylxanthine
      (selective A1 antagonist), thus excluding the participation of A1 receptors. The
      lack of effect of CGS21680 (selective A2A agonist) excluded involvement of A2A
      receptors, thus suggesting a major role for A2B receptors. Comparisons of the
      inhibitory potencies of N6-cyclopentyladenosine (selective A1 agonist), 5'-N
      ethylcarboxamidoadenosine (A1/A2 agonist), and 5'-N-methylcarboxamidoadenosine
      (A1/A2 agonist) were consistent with that of an A2B receptor subtype mediating
      the inhibitory effects. We conclude that adenosine inhibits FCS-induced collagen
      and total protein synthesis in cardiac fibroblasts via activation of A2B
      receptors. These studies suggest, but do not prove, that endogenous adenosine may
      protect against cardiac fibrosis.

PMID- 9535420
TI  - Myocardial contractile efficiency and oxygen cost of contractility are preserved
      during transition from compensated hypertrophy to failure in rats with salt
      sensitive hypertension.
AB  - In Dahl-Iwai rats, salt-sensitive hypertension causes concentric left ventricular
      hypertrophy (LVH) at the age of 11 weeks, which is followed by LV dilatation with
      global hypokinesis and pulmonary congestion, ie, LV failure (LVF), at 16 to 18
      weeks of age. To address the question of whether the cardiac remodeling from LVH
      to LVF is associated with modulations of mechanoenergetic properties, we serially
      measured the LV pressure-volume area (PVA) and myocardial oxygen consumption
      (MVO2) in isolated, isovolumically contracting hearts from this animal model. The
      end-systolic pressure-volume relationships obtained by stepwise changes of the LV
      volume were fit into a binominal regression model, which provided a value of LV
      contractility (E(es)) and a volume intercept (V0). A slope (the reciprocal of the
      LV contractile efficiency) and a PVA-independent MVO2 were determined by a
      regression analysis of the MVO2-PVA relation. The procedure was repeated at
      different Ca2+ concentrations in perfusate to estimate the oxygen cost of
      contractility (dMVO2/dE(es)). The MVO2 was further evaluated during K+-induced
      cardiac arrest to delineate the basal metabolism, which was independent of the E
      C coupling. During the transition from LVH to LVF, the E(es) was decreased by 50%
      (from 681 to 338 mm Hg x g x mL(-1), P<.001), which was associated with a
      substantial increase in V0 (from 0.002 to 0.07 mL, P<.01). These alterations in
      both the inotropic state and the ventricular shape were associated with a 45%
      decrease in the PVA-independent MVO2 (from 800 to 440 mL O2 x beat(-1) x g(-1),
      P<.01). Despite these marked changes between the two stages, both the LV
      contractile efficiency and the oxygen cost of contractility remained unchanged.
      The MVO2 during cardiac arrest also showed an equal level among the groups;
      hence, from LVH to LVF, the nonmechanical O2 consumption by the E-C coupling
      decreased in a manner parallel to the basal contractile state. We conclude that
      (1) in this animal model, the heart failure transition is associated with a
      marked decrease in myocardial contractility and with ventricular remodeling; (2)
      despite these changes, the efficiency of the chemomechanical conversion is highly
      preserved; and consequently, (3) the total energy consumption per unit of failing
      myocardium is diminished along with its reduced nonmechanical energy expenditure
      for E-C coupling. These mechanoenergetic properties might constitute an adaptive
      mechanism in the energy-starved condition of chronically diseased myocardium.

PMID- 9535421
TI  - Enalapril induces regression of cardiac hypertrophy and normalization of pHi
      regulatory mechanisms.
AB  - Intracellular pH is under strict control in myocardium; H+ are extruded from the
      cells by sodium-dependent mechanisms, mainly Na+/H+ exchanger and Na+/HCO3-
      symport, whereas Na+-independent Cl-/HCO3- exchanger extrudes bases on
      intracellular alkalinization. Hypertrophic myocardium from spontaneously
      hypertensive rats (SHR) exhibits increased Na+/H+ exchange activity that is
      accompanied by enhanced extrusion of bases through Na+-independent Cl-/HCO3-
      exchange. The present experiments were designed to investigate the effect of
      enalapril-induced regression of cardiac hypertrophy on the activity of these
      exchangers. Male SHR and normotensive Wistar-Kyoto rats (WKY) received enalapril
      maleate (20 mg/kg per day) in the drinking water for 5 weeks. Gender- and age
      matched SHR and WKY were used as untreated controls. Enalapril treatment
      significantly reduced systolic blood pressure in SHR and completely regressed
      cardiac hypertrophy. Na+/H+ activity was estimated in terms of both steady pHi
      value in HEPES buffer and the rate of pHi recovery from CO2-induced acid load.
      Na+-independent Cl-/HCO3- activity was assessed by measuring the rate of pHi
      recovery from intracellular alkalinization produced by trimethylamine exposure.
      Regression of cardiac hypertrophy was accompanied by normalization of Na+/H+ and
      Na+-independent Cl-/HCO3- exchange activities. Inhibition of protein kinase C
      (PKC) activity with chelerythrine (10 mmol/L) or calphostin C (50 nmol/L)
      returned both exchange activities to normal values. These results show that
      angiotensin-converting enzyme inhibition normalizes the enhanced activity of both
      exchangers while regressing cardiac hypertrophy. Because normalization of
      exchange activities could be also achieved by PKC inhibition, the data would
      suggest that PKC-dependent mechanisms play a significant role in the increased
      ion exchange activities of hypertrophic myocardium and in their normalization by
      angiotensin-converting enzyme inhibition.

PMID- 9535422
TI  - Spontaneously hypertensive rats: a potential model to identify drugs for
      treatment of learning disorders.
AB  - Spontaneously hypertensive rats (SHR) of 3 to 12 months of age learned and
      retrieved less information than normotensive Wistar-Kyoto rats (WKY), although no
      difference was found with animals from 18 and 24 months of age. The combined
      influence of hypertension and aging had an additive detrimental effect on
      cognitive functions. Notwithstanding these deficiencies in learning and memory,
      SHR have seldom been used as a model in the screening of drugs with therapeutic
      potential for treatment of disorders of cognitive processes. Moreover, the
      calcium channel blocker nimodipine has beneficial effects on learning in both
      aged and hypertensive animals and humans. However, no attempt has been made to
      investigate whether nimodipine can reverse the additive deleterious effects of
      aging and hypertension in the same subject. We recently reported that
      deteriorated animals (middle-aged and/or hypertensive) chronically treated with
      nimodipine (via osmotic minipumps) exhibit higher learning scores. This
      information indicates that nimodipine can reverse the impairing effects of either
      aging or hypertension on learning; the presence of the two conditions, however,
      produces a severe impairment that can be partially reversed by this drug.
      Therefore, we propose that mature and middle-aged SHR represent a model for the
      screening of potentially useful drugs in the treatment of learning disorders,
      probably associated with hypertension and/or aging. Nevertheless, it must be
      remembered that the SHR is a genetic model and the appearance of neural
      disturbances could be a parallel genetic phenomenon and not necessarily or
      exclusively related to hypertension per se.

PMID- 9535423
TI  - Chronic AT1 receptor blockade alters aortic nerve activity in hypertension.
AB  - In the chronic phase of coarctation hypertension (CH) we have shown both
      reduction in baroreceptor sensitivity (Hypertension. 1992;19[suppl II]:II-198-II
      201.) and normalization of the depressed baroreceptor reflex control of heart
      rate, even with the persistence of hypertension in losartan-treated animals (Am J
      Physiol. 1995;269:H812-H818). In the present study we analyzed the effects of
      angiotensin II blockade on afferent aortic nerve activity of CH and sham-operated
      groups treated chronically with vehicle or losartan (10 mg/kg per day p.o.). CH
      was induced by subdiaphragmatic aortic coarctation, and the treatments lasted 8
      days (4 control and 4 experimental days). Aortic pressure (conscious rats) and
      aortic nerve activity simultaneous to pressure (anesthetized rats) were recorded
      on the fourth day of the experimental period. Losartan-treated rats showed
      reduced tail pressure (104+/-3 versus 117+/-3 mm Hg in the vehicle group). In
      both groups, aortic coarctation caused a significant increase in pressure (25%
      and 28%, respectively) and a depression of the aortic nerve activity/pressure
      relationship when compared with sham-operated coarcted animals. In the
      physiological range of pressure changes, the depression was significantly smaller
      after losartan treatment (3.30+/-0.33 versus 2.18+/-0.37%/mm Hg in the losartan-
      and vehicle-treated CH groups, respectively, versus 5.05+/-0.33%/mm Hg in the
      sham-operated vehicle-treated group). Angiotensin type 1 (AT1) receptor blockade
      was also accompanied by reduced variability of the afferent discharge. The data
      suggested that apart from its pressure effect, angiotensin II acts at AT1
      receptors to decrease the sensitivity of aortic afferents during physiological
      (+/-10 mm Hg) increases and decreases in pressure. Thus, angiotensin II may
      contribute to reductions of baroreceptor gain in chronic hypertension.

PMID- 9535424
TI  - Oleic acid and angiotensin II induce a synergistic mitogenic response in vascular
      smooth muscle cells.
AB  - Oleic acid and angiotensin II (Ang II) are elevated and may interact to
      accelerate vascular disease in obese hypertensive patients. We studied the
      effects of oleic acid and Ang II on growth responses of rat aortic smooth muscle
      cells (VSMCs). Oleic acid (50 micromol/L) raised thymidine incorporation by 50%
      at 24 hours and cell number by 55% at 6 days (P<.05). Ang II (10(-11) to 10(-6)
      mol/L) did not significantly increase thymidine incorporation or VSMC number.
      Combining Ang II and 50 micromol/L oleic acid doubled thymidine incorporation and
      VSMC number. Losartan, an angiotensin type 1 (AT1) receptor antagonist, blocked
      the synergistic interaction between Ang II and oleic acid, whereas the AT2
      receptor antagonist PD 123319 did not. Protein kinase C inhibition and
      downregulation, as well as inhibition of extracellular signal-regulated kinase
      (ERK) activation by PD 98059, eliminated the rise of thymidine incorporation in
      response to oleic acid and the synergistic interaction with Ang II. However, the
      response to 10% fetal bovine serum was unaffected. An antisense
      oligodeoxynucleotide to ERK-1 and ERK-2 reduced ERK protein expression and
      activation by 83% and 75%, respectively. Antisense prevented the rise of
      thymidine incorporation in response to oleic acid and the synergy with Ang II.
      Antisense reduced but did not prevent increased thymidine incorporation in
      response to serum. The data indicate that oleic acid and Ang II exert a
      synergistic mitogenic effect in VSMCs and suggest an important role for the AT1
      receptor, PKC, and ERK in this synergy. The observations raise the possibility
      that a synergistic mitogenic interaction between oleic acid and Ang II
      accelerates vascular remodeling in obese hypertensive patients.

PMID- 9535425
TI  - Transforming growth factor-beta and receptor tyrosine kinase-activating growth
      factors negatively regulate collagen genes in smooth muscle of hypertensive rats.
AB  - Previous studies have suggested that differences in vascular smooth muscle cell
      (VSMC) proliferative responses between spontaneously hypertensive rats (SHR) and
      normotensive Wistar-Kyoto (WKY) rats can be attributed to transforming growth
      factor-beta (TGF-beta) actions. Because vascular collagen content is reported to
      be lower in SHR than in WKY rats, in this study we investigated in cell culture
      whether the differences in collagen content might also be attributed to
      differential actions of TGF-beta on VSMCs from the two strains. Exposure of VSMCs
      from WKY to the TGF-beta isoforms -beta1, -beta2, or -beta3 induced rapid,
      transient elevations in mRNAs encoding collagens alpha1(I), alpha2(I), and
      alpha1(III); maximum increases were apparent by 2 hours and ranged from twofold
      [collagen alpha1(III)] to ninefold [collagen alpha1(I)]. Thereafter they returned
      to near basal levels. When VSMCs from SHR were exposed to these TGF-beta
      isoforms, only reductions in collagen mRNA levels were observed, persisting for
      24 hours. Basic fibroblast growth factor and epidermal growth factor, factors
      known to stimulate production of the TGF-beta1 isoform in VSMCs, also induced a
      pattern of gene responses similar to those induced by the TGF-beta isoforms in
      VSMCs from SHR and WKY rats. The simultaneous presence of TGF-beta did not affect
      the time course or magnitude of the changes in collagens alpha1(I), alpha2(I), or
      alpha1(III) mRNA levels in SHR or WKY VSMCs. Examination of the induction of c
      myc mRNA and immunoreactive oncoprotein content indicated that c-myc is a likely
      contributor to the downregulation of the collagen gene activity in both SHR and
      WKY VSMCs despite the differential regulation of its mRNA by TGF-beta1 in the two
      VSMC lines. Together these data suggest that in VSMCs from SHR, a number of gene
      responses to TGF-beta, in addition to cell proliferation, appear to be abnormal
      compared with WKY rats, and the lower than normal collagen levels observed in the
      vasculature of SHR may be in part due to abnormalities in TGF-beta
      responsiveness.

PMID- 9535426
TI  - Nephroprotection of an ET(A)-receptor blocker (LU 135252) in salt-loaded
      uninephrectomized stroke-prone spontaneously hypertensive rats.
AB  - The present study was designed to assess whether the orally active and highly
      specific endothelin A (ET(A)) receptor antagonist LU 135252 affects progressive
      renal dysfunction in a hypertensive rat model of renal damage, ie, the
      uninephrectomized (UNX) stroke-prone spontaneously hypertensive rat (SHRsp). The
      animals were examined on a normal salt (0.25%) diet and, to sensitize the kidney
      to hypertensive injury, also on a high salt (3%) diet. Stereological methods were
      used to quantify indices of glomerulosclerosis, vascular damage, and
      tubulointerstitial damage. Treatment with LU 135252 (100 mg/kg body wt) did not
      affect systolic blood pressure (BP) in animals on a normal salt diet during the
      whole period of the experiment (18 weeks) or in salt-loaded animals until week
      10; subsequently, BP was slightly but significantly lower in salt-loaded UNX
      SHRsp given LU 135252. Between weeks 6 and 12, 40% of the untreated UNX-SHRsp on
      a high salt diet, but none on a standard salt diet, died; such mortality was
      completely prevented by LU 135252. Indices of renal damage were more abnormal in
      salt-loaded UNX-SHRsp compared with UNX-SHRsp on a normal salt diet. Development
      of glomerulosclerosis and tubulointerstitial and vascular damage in UNX-SHRsp on
      high salt was completely prevented by LU 135252. The respective indices were no
      longer significantly different from those of salt-loaded sham-operated SHRsp
      controls. In the less severely damaged kidneys of UNX-SHRsp on normal salt,
      treatment with LU 135252 tended to ameliorate the indices, but the difference was
      not statistically significant. The results document a role of the ET system,
      specifically of ET(A) receptors, in the development of progressive renal injury
      in salt-loaded UNX-SHRsp. LU 135252 completely prevented death and renal damage
      resulting from salt loading.

PMID- 9535427
TI  - Electroneutral Na-coupled cotransporter expression in the kidney during
      variations of NaCl and water metabolism.
AB  - The purpose of the present study was to analyze the long-term regulation of renal
      bumetanide-sensitive Na+-K+-2Cl- cotransporter and thiazide-sensitive Na+-Cl-
      cotransporter gene expression during changes in NaCl and water metabolism. Male
      Wistar rats exposed to high or low NaCl intake, saline loading, dehydration,
      water loading, and furosemide administration during 7 days were studied. Control
      groups had access to regular food and tap water. Rats were kept in metabolic
      cages for 4 days before and during the experiment to determine daily urinary
      electrolyte excretion and osmolarity. At the end of the experiment, creatinine
      clearance and serum electrolyte levels were also measured. Kidneys were excised
      and macroscopically subdivided into cortex and outer and inner medulla. Total RNA
      was extracted from each individual cortex or outer medulla by use of the
      guanidine/cesium chloride method. The Na+-K+-2Cl- cotransporter expression in
      outer medulla total RNA was assessed by nonradioactive Northern blot analysis and
      the Na+-Cl- cotransporter expression in renal cortex total RNA was assessed by
      semiquantitative polymerase chain reaction. Experimental maneuvers were
      adequately tolerated, and all groups developed the appropriate renal response to
      each challenge. However, the level of expression of both cotransporters did not
      change in any model, except for a 2.8-fold increase in the Na+-Cl- cotransporter
      expression during dehydration. We conclude that nephron adaptation to 7-day
      modifications in NaCl and water metabolism does not include changes in the amount
      of electroneutral sodium-coupled cotransporter gene expression at the mRNA level.

PMID- 9535428
TI  - Perindopril treatment affects both preglomerular renal vascular lumen dimensions
      and in vivo responsiveness to vasoconstrictors in spontaneously hypertensive
      rats.
AB  - We have previously shown that chronic treatment with angiotensin-converting
      enzyme inhibition (ACEI) did not reverse hypertrophy of the renal arterial wall
      in spontaneously hypertensive rats (SHR). In this study we determined the effects
      of perindopril on the functional properties of the renal vasculature in vivo and
      on its resistance to flow at maximal dilatation in vitro, a measure of vessel
      lumen diameter. Two groups of SHR were studied: untreated or treated with
      perindopril (3 mg/kg per day) in their drinking water from 4 weeks of age. At 10
      weeks, (1) vessel lumen characteristics were assessed using a maximally dilated
      in vitro isolated kidney perfusion and (2) the renal vasoconstrictor responses to
      bolus doses of vasoactive agents (angiotensin II and phenylephrine) administered
      into the renal artery were measured in vivo (anesthetized rats). Mean arterial
      pressure was significantly lower in conscious SHR treated with perindopril (132+/
      2 versus 97+/-2 mm Hg, P<.001). In vitro, the pressure-flow relationship and the
      pressure-glomerular filtration rate relationship were both shifted significantly
      to the left (P<.001). The perindopril-treated kidneys began filtering at a
      significantly lower threshold perfusion pressure than nontreated controls
      (P<.001). In vivo, renal vasoconstrictor responses to increasing doses of both
      vasoconstrictor agents were significantly less marked in the perindopril-treated
      SHR than in untreated SHR (P<.05). Thus, chronic ACEI increased average renal
      vessel lumen diameter in SHR, predominantly in preglomerular vessels, and reduced
      renal vasoconstrictor responsiveness in vivo, findings compatible with remodeling
      of the preglomerular vasculature around a greater lumen.

PMID- 9535430
TI  - White coat effect and reactivity to stress: cardiovascular and autonomic nervous
      system responses.
AB  - The aim of this study was to elucidate further the precise nature of the so
      called "white coat" (WC) effect. We enrolled 88 hypertensive (46 men, 42 women)
      and 18 normotensive (4 men, 14 women) subjects in whom beat-to-beat blood
      pressure (BP) and heart rate (HR) were measured with a Finapres device at rest (R
      period) and during conventional BP measurement (WC period). The WC effect was
      defined as WC period minus R period values of Finapres systolic BP. Using the
      same method, we also measured the BP and HR variations induced by mental stress
      (MS period) and by assuming the standing position (S period). Variability was
      estimated in the frequency domain for BP (BPV) and HR (HRV) and gave indices of
      the autonomic nervous system. Pulse wave velocity was taken as an index of
      arterial distensibility. In hypertensive subjects, the WC effect was
      significantly and positively correlated with the BP response to stress (0.51,
      P<.0001) and standing (0.63, P<.0001). An increased BPV was observed in the low
      frequency band (0 to 0.150 Hz) during WC, MS, and S periods. In normotensive
      subjects, the WC effect was very slight and not correlated with the responses to
      stress and standing. In this group, the WC period was not accompanied with an
      increased BPV, unlike the stress and standing periods. HRV was similar in
      normotensives and in hypertensives: decreased, unchanged, and increased during
      MS, S, and WC periods, respectively. The PWV was significantly increased in the
      hypertensives relative to the normotensives, even in the quartile of those with
      the lowest BP (on average similar to that of the normotensives). This work shows
      that the WC effect is associated with an enhanced BP response to standing and
      mental stress; these three situations are characterized by an increased BPV in
      the low frequencies, suggesting a similar modification of the sympathovagal
      balance. The WC effect may entail an increased risk because it is associated with
      impaired arterial distensibility.

PMID- 9535429
TI  - Hypertension optimal treatment (HOT) study: home blood pressure in treated
      hypertensive subjects.
AB  - The Hypertension Optimal Treatment Study is a prospective trial conducted in 26
      countries. The aims are to (1) evaluate the relationship between three levels of
      target office diastolic blood pressure (BP) (< or = 80, < or = 85, or < or = 90
      mm Hg) and cardiovascular morbidity and mortality in hypertensive patients and
      (2) examine the effects on cardiovascular morbidity and mortality of 75 mg
      aspirin daily versus placebo. A total of 19,193 patients between 50 and 80 years
      of age had been randomized by the end of April 1994. Treatment was initiated with
      felodipine 5 mg daily, and additional therapy was given in accordance with a set
      protocol. The present substudy of 926 patients performed in nine countries aimed
      to (1) compare home with office BP in a representative subsample of the HOT
      population after the titration of treatment was completed and (2) clarify whether
      the separation into the target groups could be expanded into the out-of-office
      setting. The differences between office and home measurements in diastolic BP of
      0.2 mm Hg (SD, 9; 95% confidence interval, -0.36 to 0.81; P=.40) and systolic BP
      of 0.5 mm Hg (SD, 15; 95% confidence interval, -0.53 to 1.46; P=.21) were not
      significant. The group differences in home BP were 1.9 mm Hg (< or = 80 versus <
      or = 85) and 1.2 mm Hg (< or = 85 versus < or = 90) for diastolic BP (F=11.69;
      ANOVA, P<.0001) and 2.6 and 2.1 mm Hg for systolic BP (F=8.44, P=.0002). Thus,
      office and home BPs measured with the same semiautomatic device are comparable in
      treated hypertensive subjects in the HOT Study, and the separation into the
      target groups based on office readings prevails at home.

PMID- 9535431
TI  - Enhanced depressor response to nitric oxide in the rostral ventrolateral medulla
      of spontaneously hypertensive rats.
AB  - Possible impairment of the L-arginine-nitric oxide (NO) pathway in the rostral
      ventrolateral medulla of adult spontaneously hypertensive rats (SHR) was
      investigated by microinjecting N(G)-nitro-L-arginine methyl ester (L-NAME), NOC
      18 (an NO donor), or L-arginine. Unilateral injection of L-NAME (10 nmol/50 nL)
      into the rostral ventrolateral medulla significantly increased mean arterial
      pressure (MAP) in both SHR and Wistar-Kyoto rats (WKY). The increases in MAP did
      not differ significantly between the two strains (15+/-3 versus 10+/-2 mm Hg,
      respectively; n=8). In contrast, microinjection of L-arginine elicited
      significant (P<.05) dose-dependent decreases in MAP in both strains, and these
      depressor responses were significantly greater in SHR than in WKY (in 10 nmol of
      L-arginine: -29+/-2 versus -15+/-2 mm Hg, respectively; n=8, P<.01). Similarly,
      microinjection of NOC 18 (10 nmol/50 nL) reduced MAP in both strains, and the
      depressor response was also significantly greater in SHR than in WKY (-38+/-7
      versus -22+/-3 mm Hg, respectively; n=8, P<.05). These results suggest that the L
      arginine-NO pathway in the rostral ventrolateral medulla is impaired in SHR and
      that this impairment may contribute to the increase in arterial pressure in this
      animal model of genetic hypertension.

PMID- 9535432
TI  - Endothelin-1 regulates tone of isolated small arteries in the rat: effect of
      hyperendothelinemia.
AB  - Chronic elevation of plasma endothelin-1 (ET-1) levels has been reported in
      several pathological conditions. To investigate the consequences of increased
      circulating ET-1 on vascular responsiveness, Sprague-Dawley rats (n=16) were
      chronically instrumented with a minipump delivering ET-1 at a constant dose for 7
      days. Plasma ET-1 levels were more than doubled in treated (0.98+/-0.09 pmol/L;
      P<.05) versus untreated sham-operated rats (0.43+/-0.04 pmol/L), whereas systolic
      arterial blood pressure increased (139+/-5 versus 128+/-4 mm Hg in untreated
      rats; P<.05). After rats were killed, segments of middle cerebral (MCA) and
      mesenteric (MES) arteries were mounted on an isometric myograph. ET-induced
      contraction was shifted to the right in ET-1-treated animals and not modified by
      BQ123 (an ET(A) receptor antagonist); bosentan (ET(A/B) receptor antagonist)
      prevented ET-1-induced contraction in both groups. After inhibition of nitric
      oxide synthase with N(omega)-nitro-L-arginine (L-NNA), both phenylephrine and
      oxymetazoline (an alpha2-adrenoceptor agonist) induced MCA contraction. The
      sensitivity to phenylephrine was decreased in ET-1-treated compared with control
      rats (P<.05). Sensitivity to phenylephrine-induced contraction was decreased by
      BQ123 in control rats only. In contrast, L-NNA revealed greater oxymetazoline
      induced contractions in treated compared with control MCA rings (P<.05); this
      potentiation was blunted by bosentan but unaffected by BQ123. Removal of the
      endothelium revealed a direct constrictor effect of oxymetazoline that was
      insensitive to L-NNA alone or combined with bosentan; however, oxymetazoline
      induced significantly lower constriction in treated rat MCA segments. Responses
      to oxymetazoline were also blunted in treated compared with untreated denuded MES
      arteries. In conclusion, chronic elevated plasmatic ET-1 decreases smooth muscle
      cell sensitivity to contractile agonists both in MCA and MES rings. In cerebral
      vessels, endothelial alpha2-adrenoceptor-dependent stimulation induced greater
      contractile responses in treated rats which were sensitive to bosentan,
      suggesting that oxymetazoline stimulates ET-1 release from the endothelium. This
      may represent a compensatory mechanism for the loss of smooth muscle sensitivity.

PMID- 9535433
TI  - The Working Group report of Science-Based Categories for abstracts submitted to
      the annual Scientific Sessions. The Committee on Scientific Sessions Program
      (CSSP), American Heart Association.

PMID- 9535434
TI  - Thromboembolic complications after fontan procedures--the role of prophylactic
      anticoagulation.

PMID- 9535435
TI  - Arrhythmias and thromboembolic complications after the extracardiac Fontan
      operation.
AB  - BACKGROUND: Late morbidity and mortality after the Fontan operation are largely
      due to atrial arrhythmias, ventricular failure, and thrombus formation. The
      extracardiac Fontan procedure avoids extensive atrial manipulation and suture
      lines, theoretically minimizing the impetus for these events. We examined our
      experience with the extracardiac Fontan operation with particular attention to
      thromboembolism and arrhythmias. METHODS AND RESULTS: We retrospectively reviewed
      the medical and surgical records of all 16 patients who underwent an extracardiac
      Fontan operation between July 1993 and May 1996. Fifteen patients (94%) were in
      sinus rhythm before the operation. In the immediate postoperative period, seven
      (44%) had arrhythmias consisting of accelerated junctional rhythm and ectopic
      atrial rhythm. No associated hemodynamic compromise and no early deaths occurred.
      Patients were followed up for 3 to 34 months after the Fontan operation.
      Arrhythmias were detected in eight patients (50%) on surface electrocardiograms,
      and seven (44%) showed evidence of sinus node dysfunction on 24-hour Holter
      monitor studies. Thrombi were found in three patients (19%). All patients were
      asymptomatic, with no evidence of conduit obstruction by echocardiogram.
      CONCLUSIONS: The incidence of hemodynamically significant tachyarrhythmias
      appears to be reduced after the extracardiac Fontan operation. A significant
      percentage of patients have evidence of sinus node dysfunction, suggesting the
      presence of other surgical or nonsurgical factors responsible for this finding.
      Our incidence of thrombotic events is similar to previous reports with other
      Fontan modifications. It appears to be a reasonable option to maintain these
      patients on anticoagulation indefinitely.

PMID- 9535436
TI  - Fate of subpulmonary homograft conduits: determinants of late homograft failure.
AB  - PATIENTS AND METHODS: Between 1971 and 1993, 656 conduits were placed in the
      subpulmonary position. Patients receiving heterografts or valveless conduits and
      patients dying within 90 days of insertion were excluded; thus 405 homograft
      conduits were studied. There were 293 aortic homografts, 94 pulmonary, and 18 of
      unknown type. The end point of conduit failure was defined by conduit replacement
      for whatever reason, balloon dilation of the conduit, or death of the patient
      with the conduit in place. The following factors were analyzed: aortic versus
      pulmonary homograft, antibiotic preservation versus cryopreservation, ABO and Rh
      compatibility, type of material used for conduit extension, age at operation,
      size of the conduit, diagnosis, and reoperations. Conduit number (1 to 405) in
      the series was included in the multivariable model. RESULTS: First conduits and
      conduits inserted earlier in the series appeared to last longer than second and
      subsequent conduits and those inserted later in the series (p = 0.001 and 0.003,
      respectively). Overall survival of conduits at 5, 10, and 15 years was 84% (95%
      CL, 80% to 88%), 58% (95% CL, 50% to 66%), and 31% (95% CL, 19% to 43%).
      Corresponding figures for the first conduits were 88% (95% CL, 84% to 92%), 65%
      (95% CL, 56% to 73%), and 34% (95% CL, 20% to 47%). The longest surviving
      homograft conduit in our series lasted 22.7 years. Regarded univariately,
      reoperation (redo worse), order number (recent worse), type of conduit (pulmonary
      worse than aortic), preservation (cryopreserved worse than antibiotic preserved),
      and age at operation (older patients worse) were statistically significant.
      However, in multivariable analysis, including all the above in the model, only
      reoperation and order number had significant predictive power. When patient
      survival was considered, patients operated on more recently survived longer
      despite the fact that their conduits were being replaced earlier. Overall,
      survival of patients at 5 and 15 years was 95% (95% CL, 93% to 98%) and 85% (95%
      CL, 77% to 92%), respectively. CONCLUSIONS: Pulmonary and aortic homografts, both
      cryopreserved and preserved in nutrient antibiotic solution, give similar
      results. All conduits will probably have to be replaced during the lifetime of
      the patient. In view of the worse performance of replacement conduits, techniques
      of repair that avoid the use of conduits should be further explored. Despite
      gradual deterioration of homograft conduits, they remain an important tool in the
      correction of many complex lesions with excellent 15-year patient survival.

PMID- 9535437
TI  - Dilutional and modified ultrafiltration reduces pulmonary hypertension after
      operations for congenital heart disease: a prospective randomized study.
AB  - OBJECTIVE: A prospective randomized study was performed to test whether removal
      of endothelin-1, by ultrafiltration techniques, will reduce pulmonary
      hypertension after operations for congenital heart disease. METHODS: Twenty-four
      patients with pulmonary hypertension (systolic pulmonary/systemic arterial
      pressure ratio > 60%) undergoing cardiac operations were randomized into a
      control group (n = 12) having conventional ultrafiltration and an experimental
      group (n = 12) undergoing dilutional ultrafiltration during and modified
      ultrafiltration after cardiopulmonary bypass. Plasma endothelin-1, nitric oxide
      metabolites, and cyclic guanosine monophosphate were assayed before bypass, 10
      minutes into bypass, after bypass, and 0, 3, 6, and 12 hours after the operation
      in both groups, as well as in the ultrafiltrates and after modified
      ultrafiltration in the experimental group. Both groups received alpha-blockers
      (chlorpromazine and/or prazosin) postoperatively using the same guidelines.
      RESULTS: The ultrafiltrates contained significant amounts of endothelin-1 (1.81
      +/- 0.86 pg/ml, dilutional, and 6.44 +/- 1.82 pg/ml, modified ultrafiltrate).
      Endothelin-1 and the pulmonary/systemic pressure ratio were significantly lower
      in experimental compared with control patients. Nitric oxide metabolites and
      cyclic guanosine monophosphate increased similarly in both groups for 12 hours
      after the operation (p = not significant). Three of 12 control patients (25%) but
      no experimental patients had pulmonary hypertensive crises (p = 0.07). The
      experimental patients required significantly less ventilatory support (67 +/- 47
      hours vs 178 +/- 139 hours for control patients, p = 0.048). CONCLUSIONS:
      Dilutional and modified ultrafiltration reduce endothelin-1 and the
      pulmonary/systemic pressure ratio postoperatively and may become an important
      adjunct for preventing pulmonary hypertension after operations for congenital
      heart disease in high-risk patients.

PMID- 9535438
TI  - Liquid ventilation improves pulmonary function and cardiac output in a neonatal
      swine model of cardiopulmonary bypass.
AB  - OBJECTIVE: Neonatal and infant cardiopulmonary bypass results in multiorgan
      system dysfunction. Organ protective strategies have traditionally been directed
      at the myocardium and brain while neglecting the sometimes severe injury to the
      lungs. We hypothesized that liquid ventilation would improve pulmonary function
      and cardiac output in neonates after cardiopulmonary bypass. METHODS: Twenty
      neonatal swine were randomized to receive cardiopulmonary bypass with or without
      liquid ventilation. In the liquid-ventilated group, a single dose of perflubron
      was administered before bypass. The control group was conventionally ventilated.
      Each animal was placed on nonpulsatile, hypothermic bypass. Low-flow
      cardiopulmonary bypass was performed for 60 minutes. The flow rate was returned
      to 125 ml/kg per minute, and after warming to 37 degrees C, the animals were
      removed from bypass. Hemodynamic and ventilatory data were obtained after bypass
      to assess the effects of liquid ventilation. RESULTS: Without liquid ventilation,
      cardiopulmonary bypass resulted in a significant decrease in cardiac output,
      oxygen delivery, and static pulmonary compliance compared with prebypass values.
      Input pulmonary resistance and characteristic impedance increased in these
      control animals. At 30, 60, and 90 minutes after bypass, the animals receiving
      liquid ventilation showed significantly increased cardiac output and static
      compliance and significantly decreased input pulmonary resistance and
      characteristic impedance compared with control animals not receiving liquid
      ventilation. CONCLUSIONS: Liquid ventilation improved pulmonary function after
      neonatal cardiopulmonary bypass while increasing cardiac output. The morbidity
      associated with cardiopulmonary bypass may be significantly reduced if the
      adverse pulmonary sequelae of bypass can be diminished. Liquid ventilation may
      become an important technique to protect the lungs from the deleterious effects
      of cardiopulmonary bypass.

PMID- 9535439
TI  - Creation of viable pulmonary artery autografts through tissue engineering.
AB  - BACKGROUND: "Repair" of many congenital cardiac defects requires the use of
      conduits to establish right ventricle to pulmonary artery continuity. At present,
      available homografts or prosthetic conduits lack growth potential and can become
      obstructed by tissue ingrowth or calcification leading to the need for multiple
      conduit replacements. Tissue engineering is an approach by which cells are grown
      in vitro onto biodegradable polymers to construct "tissues" for implantation. A
      tissue engineering approach has recently been used to construct living cardiac
      valve leaflets from autologous cells in our laboratory. This study assesses the
      feasibility of a tissue engineering approach to constructing tissue-engineered
      "living" pulmonary artery conduits. MATERIALS AND METHODS: Ovine artery (group A,
      n = 4) or vein (group V, n = 3) segments were harvested, separated into
      individual cells, expanded in tissue culture, and seeded onto synthetic
      biodegradable (polyglactin/polyglycolic acid) tubular scaffolds (20 mm long x 15
      mm diameter). After 7 days of in vitro culture, the autologous cell/polymer
      vascular constructs were used to replace a 2 cm segment of pulmonary artery in
      lambs (age 68.4 +/- 15.5 days, weight 18.7 +/- 2.0 kg). One other control animal
      received an acellular polymer tube sealed with fibrin glue without autologous
      cells. Animals were sacrificed at intervals of 11 to 24 weeks (mean follow-up
      130.3 +/- 30.8 days, mean weight 38.9 +/- 13.0 kg) after echocardiographic and
      angiographic studies. Explanted tissue-engineered conduits were assayed for
      collagen (4-hydroxyproline) and calcium content, and a tissue deoxyribonucleic
      acid assay (bis-benzimide dye) was used to estimate number of cell nuclei as an
      index of tissue maturity. RESULTS: The acellular control graft developed
      progressive obstruction and thrombosis. All seven tissue-engineered grafts were
      patent and demonstrated a nonaneurysmal increase in diameter (group A = 18.3 +/-
      1.3 mm = 95.3% of native pulmonary artery; group V = 17.1 +/- 1.2 mm = 86.8% of
      native pulmonary artery). Histologically, none of the biodegradable polymer
      scaffold remained in any tissue-engineered graft by 11 weeks. Collagen content in
      tissue-engineered grafts was 73.9% +/- 8.0% of adjacent native pulmonary artery.
      Histologically, elastic fibers were present in the media layer of tissue
      engineered vessel wall and endothelial specific factor VIII was identified on the
      luminal surface. Deoxyribonucleic acid assay showed a progressive decrease in
      numbers of cell nuclei over 11 and 24 weeks, suggesting an ongoing tissue
      remodeling. Calcium content of tissue-engineered grafts was elevated (group A =
      7.95 +/- 5.09; group V = 13.2 +/- 5.48; native pulmonary artery = 1.2 +/- 0.8
      mg/gm dry weight), but no macroscopic calcification was found. CONCLUSIONS:
      Living vascular grafts engineered from autologous cells and biodegradable
      polymers functioned well in the pulmonary circulation as a pulmonary artery
      replacement. They demonstrated an increase in diameter suggesting growth and
      development of endothelial lining and extracellular matrix, including collagen
      and elastic fibers. This tissue-engineering approach may ultimately allow the
      development of viable autologous vascular grafts for clinical use.

PMID- 9535440
TI  - Fontan conversion to cavopulmonary connection and arrhythmia circuit cryoblation.
AB  - OBJECTIVES: We review our surgical experience patients with atriopulmonary Fontan
      operations who had obstructive or arrhythmia indications for conversion to total
      cavopulmonary artery connections, arrhythmia circuit cryoablation, and placement
      of atrial antitachycardia pacemaker. METHODS: Fourteen patients (mean age 14 +/-
      4 years) had conversion to total cavopulmonary artery connection 8 +/- 3 years
      after the original atriopulmonary Fontan operation primarily for atrial
      arrhythmias in 11, obstructive lesions in 2, and bradycardia with cyanosis in 1.
      Arrhythmia circuit cryoablation was performed on 11 patients and 10 had atrial
      antitachycardia pacemakers. Preoperative functional New York Heart Association
      class was IV in 9, III in 4, and II in 1. RESULTS: One patient had brain death
      (7%) presumably caused by resternotomy complications despite an excellent
      hemodynamic result. Another required reoperation for a maldeployed clamshell
      device after attempted fenestration closure. Average length of stay was 10 +/- 3
      days; chest tubes were removed on day 7 +/- 3. There were no long-term deaths
      (mean follow-up 1.7 years, range 5 months to 5 years). Postoperative arrhythmias
      occurred in five patients, three of whom had successful termination by
      antitachycardia pacemaker and two who had pharmacologic control of their
      respective junctional ectopic and slow atrial tachycardia. All patients have
      improved to New York Heart Association class I or II. CONCLUSIONS: Total
      cavopulmonary artery conversion in association with arrhythmia circuit
      cryoablation and atrial antitachycardia pacemaker placement can be accomplished
      with low morbidity and mortality, oftentimes resulting in dramatic increases in
      functional class and control of life-threatening arrhythmias.

PMID- 9535441
TI  - Fate of the neopulmonary valve after the arterial switch operation in neonates.
AB  - OBJECTIVES: The purpose of this study was to determine the incidence, risk
      factors, and outcomes of acquired stenosis of the neopulmonary valve after the
      neonatal arterial switch operation. METHODS: Reviewed were the preoperative and
      follow-up echocardiograms from 136 of 288 patients undergoing the arterial switch
      operation for whom adequate studies were available. Pulmonary stenosis was
      defined as a thickened and doming pulmonary valve and a pressure gradient of 20
      mm Hg or more. Transposition of the great arteries was present with intact
      ventricular septum in 91 patients, with a ventricular septal detect in 39, with
      an aortic coarctation in 5, and with double-outlet right ventricle in 1 patient.
      No patient had preoperative valvular abnormalities (i.e., a bicuspid valve).
      RESULTS: During a median follow-up of 18 months (range <1 to 90 months), 32
      patients (24%) had the development of supravalvular pulmonary stenosis, 15 (11%)
      with associated pulmonary valve stenosis (group I). Kaplan-Meier estimates of
      freedom from any intervention were 94% (95% confidence interval, 90% to 99%) at 1
      year and 79% (95% confidence interval, 64% to 94%) at 5 years. The valve anulus
      before the arterial switch operation was significantly larger (p < 0.03) in those
      in whom neopulmonary valve stenosis did not develop (group II) than it was in
      those in whom it did (group I). At follow-up, the pulmonary valve anulus had
      decreased significantly in diameter in group I (p < 0.0005) and had remained
      larger in group II (p = 0.06) compared with normal diameter. Group I patients had
      the development of significant pulmonary valve hypoplasia (p < 0.03) whereas
      group II patients continued to have significantly larger valves compared with
      normal size (p < 0.0001). CONCLUSIONS: Neopulmonary valve stenosis after the
      arterial switch operation is not uncommon and is associated with growth failure
      of the valve anulus often associated with supravalvular pulmonary stenosis.

PMID- 9535442
TI  - Editorial (con) re minimally invasive port-access mitral valve surgery.

PMID- 9535443
TI  - Editorial (pro) re minimally invasive port-access mitral valve surgery.

PMID- 9535444
TI  - Minimally invasive port-access mitral valve surgery.
AB  - OBJECTIVES: This study evaluates the feasibility of video-assisted minimally
      invasive mitral valve surgery by means of the Port-Access system. The aim of the
      study was to minimize surgical access and to develop a video-assisted surgical
      technique. METHODS: The Port-Access system allows for closed chest endoluminal
      aortic clamping, cardioplegic arrest, and decompression of the heart. The mitral
      valve was either repaired (n = 28) or replaced (n = 23) in 51 patients by means
      of a minimally invasive approach through a right lateral minithoracotomy and
      under videoscopic guidance. RESULTS: Mean length of incision was 5.4 +/- 1.8 cm
      (range 3.8 to 8 cm). Mean duration of operation, cardiopulmonary bypass, and
      crossclamp time was 196 +/- 53, 133 +/- 52, and 72 +/- 27 minutes, respectively.
      Median intubation time was 25.5 hours (range 5 to 264 hours). Median duration of
      intensive care and hospital stay was 2 days (range 1 to 36 days) and 13 days (10
      to 36 days), respectively. Hospital mortality was 9.8% (5/51). Overall morbidity
      was relatively high. In two patients acute retrograde aortic dissection led to
      conversion of the procedure. At follow-up (261 +/- 13 days), three patients
      required reoperation for paravalvular leakage. Baseline mean Duke activity index
      score was 19.3 +/- 11.3 before the operation and increased to 23.2 +/- 10 at 6
      weeks' and 24.2 +/- 10.3 at 12 weeks' follow-up, respectively. CONCLUSION: The
      Port-Access system allows for video-assisted minimally invasive replacement and
      complex repair of the mitral valve through a right lateral minithoracotomy.
      However, morbidity and mortality associated with this novel technique were high.

PMID- 9535445
TI  - Prophylactic replacement of Bjork-Shiley convexo-concave valves at risk of strut
      fracture. Bjork-Shiley Study Group.
AB  - OBJECTIVE: Prophylactic replacement of Bjork-Shiley convexo-concave valves
      (Shiley, Inc., Irvine, Calif.) has been advised for selected groups of patients.
      If prophylactic replacement is considered, risks of postoperative morbidity and
      mortality have to be weighed against benefits of replacement. Here we report the
      results of prophylactic replacement of Bjork-Shiley convexo-concave valves at
      risk of strut fracture in The Netherlands. METHODS: We reviewed medical records
      of 36 patients undergoing prophylactic replacement of their Bjork-Shiley convexo
      concave valves before August 1995. Replacement was judged to be prophylactic if
      the risk of strut fracture outweighed that of death from reoperation, or the
      patient wished to have the valve replaced although it was not recommended. The
      procedure was also considered to be prophylactic if a concomitant pathologic
      condition, not likely to require cardiac surgery in the near future, was present
      or if preoperative examination revealed an unexpected cardiac pathologic
      condition. RESULTS: Twenty-two 70-degree and 16 60-degree Bjork-Shiley convexo
      concave valves and one spherical valve were replaced (25 aortic and 14 mitral,
      including three double-valve replacements). Early mortality was 2.8% (1/36)
      (exact 95% confidence interval [CI] 0.1 to 14.5). Mean follow-up was 33 months.
      One- and 3-year survivals were 94% (95% CI 79% to 99%) and 91% (95% CI 74% to
      97%), respectively. All three deaths were sudden. CONCLUSIONS: If special care is
      taken in selecting patients, the risk of prophylactic replacement is comparable
      to that of primary valve replacement. More data are needed to assess whether the
      risk of sudden death is possibly increased.

PMID- 9535446
TI  - In vivo accuracy of two radiographic systems in the detection of Bjork-Shiley
      convexo-concave heart valve outlet strut single leg separations.
AB  - OBJECTIVE: Modified cineradiographic systems have been used clinically to detect
      partially broken outlet struts in normally functioning Bjork-Shiley convexo
      concave heart valves. Almost all such valves were explanted, presuming that full
      failure would likely follow. Inasmuch as the clinical setting only rarely permits
      examination of normally rated valves, the accuracy of radiographic detection
      cannot be clinically defined. This study uses the clinical radiographic technique
      in sheep implanted with known-status convexo-concave valves, comparing its
      accuracy and that of a newly developed, geometric image magnification radiography
      system. METHODS: Twenty-one sheep with mitral convexo-concave valves were studied
      on both systems. Five were used for extensive training. When operators were
      expert with both systems, images of four intact valves and 12 valves with outlet
      strut single leg separations, along with a seventeenth single leg separation
      valve used for calibration, were integrated into 112 image sets organized into a
      balanced incomplete block design for evaluation by eight trained, blinded
      reviewers. RESULTS: Cineradiography sensitivity was 24% versus 31% for direct
      image magnification. The odds ratio for detection of single leg separation by
      direct image magnification versus cineradiography was 2.0 (95% confidence
      interval, 0.76 to 5.9; p = 0.13). Cineradiography specificity was 93% versus 90%
      for direct image magnification. Sensitivity and specificity varied markedly by
      reviewer, with sensitivity ranging from 8% to 55% and specificity from 51% to
      100% for the combined technologies. CONCLUSIONS: The data support the need for
      more intensive training for convexo-concave valve imaging and further
      investigation of unconventional radiographic technologies. Clinical
      cineradiography of convexo-concave valves may detect as little as 25% of valves
      having a single leg separation, underestimating the prevalence of single leg
      separations and thereby implying more rapid progression to full fracture than is
      actually the case.

PMID- 9535447
TI  - Operative outcome and hospital cost.
AB  - INTRODUCTION: Because of concern about increasing health care costs, we undertook
      a study to find patient risk factors associated with increased hospital costs and
      to evaluate the relationship between increased cost and in-hospital mortality and
      serious morbidity. METHODS: More than 100 patient variables were screened in 1221
      patients undergoing cardiac procedures. Simultaneously, patient hospital costs
      were computed from the cost-to-charge ratio. Univariate and multivariate
      statistics were used to explore the relationship between hospital cost and
      patient outcomes, including operative death, in-hospital morbidity, and length of
      stay. RESULTS: The greatest costs were for 31 patients who did not survive
      operation ($74,466, 95% confidence interval $27,102 to $198,025), greater than
      the costs for 120 patients who had serious, nonfatal morbidity ($60,335, 95%
      confidence interval $28,381 to $130,897, p = 0.02) and those for 1070 patients
      who survived operation without complication ($31,459, 95% confidence interval
      $21,944 to $49,849, p = 0.001). Breakdown of the components of hospital costs in
      fatalities and in cases with nonfatal complications revealed that the greatest
      contributions were in anesthesia and operating room costs. Significant (by
      stepwise linear regression analysis) independent risks for increased hospital
      cost were as follows (in order of decreasing importance): (1) preoperative
      congestive heart failure, (2) serum creatinine level greater than 2.5 mg/dl, (3)
      New York state predicted mortality risk, (4), type of operation (coronary artery
      bypass grafting, valve, valve plus coronary artery bypass grafting, or other),
      (5) preoperative hematocrit, (6) need for reoperative procedure, (7) operative
      priority, and (8) sex. These risks were different than those for in-hospitality
      death or increased length of stay. Hospital cost correlated with length of stay
      (r = 0.63, p < 0.001), but there were many outliers at the high end of the
      hospital cost spectrum. CONCLUSIONS: We conclude that operative death is the most
      costly outcome; length of stay is an unreliable indicator of hospital cost,
      especially at the high end of the cost spectrum; risks of increased hospital cost
      are different than those for perioperative mortality or increased length of stay;
      and ventricular dysfunction in elderly patients undergoing urgent operations for
      other than coronary disease is associated with increased cost. Certain patient
      factors, such as preoperative anemia and congestive heart failure, are amenable
      to preoperative intervention to reduce costs, and a high-risk patient profile can
      serve as a target for cost-reduction strategies.

PMID- 9535448
TI  - Perivascular delivery of a nitric oxide donor inhibits neointimal hyperplasia in
      vein grafts implanted in the arterial circulation.
AB  - OBJECTIVE: Nitric oxide has been reported to reduce intimal hyperplasia as a
      response to arterial injury. This study was designed to assess the possible
      effect of perivascular application of a nitric oxide donor on neointimal
      proliferation occurring in veins exposed to the dynamics of the arterial
      circulation in a hypercholesterolemic rabbit model. METHODS: Autologous jugular
      vein grafts were implanted in the carotid circulation of 20 hypercholesterolemic
      rabbits. A mixture of a biodegradable polymer and the nitric oxide donor,
      spermine/nitric oxide, which releases nitric oxide with a half-life of 39
      minutes, was applied periadventitially at the time of implantation. Controls were
      veins bathed in saline solution, polymer alone, and polymer plus the carrier
      vehicle spermine without nitric oxide. Animals (n = 5 in each group) were put to
      death on day 28 for morphometric analysis, cell count, and immunohistochemical
      staining. RESULTS: Treatment with perivascular nitric oxide donor significantly
      decreased wall thickness (126 +/- 24 microm vs 208 +/- 45 microm, p = 0.0017) and
      area (124 +/- 22 microm2/microm vs 211 +/- 37 microm2/microm, p = 0.005). With
      the carrier vehicle spermine alone, there was a trend toward reduced intimal
      thickness, but the change was not statistically significant. In the grafts
      treated with nitric oxide donor, expression of insulin-like growth factor,
      fibroblast growth factor, thrombospondins, fibronectin, and tenascin was reduced.
      CONCLUSION: The periadventitial delivery of nitric oxide donor produces a
      reduction of neointimal hyperplasia in veins implanted in the arterial
      circulation. The mechanism of action is not entirely clear, but the reduction
      cannot be explained on the basis of decreased cell proliferation alone. Other
      possibilities are modulation of protein synthesis of vascular smooth muscle cells
      and production of extracellular matrix components.

PMID- 9535449
TI  - Infarct size and location determine development of mitral regurgitation in the
      sheep model.
AB  - OBJECTIVE: This study tests the hypothesis that neither small nor large
      myocardial infarctions that include the anterior papillary muscle produce mitral
      regurgitation in sheep. METHODS: Coronary arterial anatomy to the anterior left
      ventricle and papillary muscle was determined by dye injection in 41 sheep hearts
      and by triphenyl tetrazolium chloride in 13. Development of acute or chronic
      mitral regurgitation and changes in left ventricular dimensions were studied by
      use of transdiaphragmatic echocardiography in 21 sheep after infarction of 24%
      and 33% of the anterior left ventricular mass. These data were compared with
      previous data from large and small posterior left ventricular infarctions.
      RESULTS: Ligation of two diagonal arteries infarcts 24% of the left ventricular
      mass and 82% of the anterior papillary muscle. Ligation of both diagonals and the
      first circumflex branch infarcts 33% of the left ventricle and all of the
      anterior papillary muscle. Neither infarction causes mitral regurgitation,
      although left ventricular cavity dimensions increase significantly at end
      systole. After the smaller infarction, the left ventricular cavity enlarges 150%
      over 8 weeks without mitral regurgitation. CONCLUSIONS: In sheep small and large
      infarctions of the anterior wall that include the anterior papillary muscle do
      not produce either acute or chronic mitral regurgitation despite left ventricular
      dilatation. In contrast large posterior infarctions produce immediate mitral
      regurgitation owing to asymmetric annular dilatation and discoordination of
      papillary muscle relationships to the valve. After small posterior infarctions
      that include the posterior papillary muscle, mitral regurgitation develops
      because of annular and ventricular dilatation during remodeling.

PMID- 9535450
TI  - Ex vivo adenovirus-mediated gene transfer to the adult rat heart.
AB  - OBJECTIVE: The ability to transfer genes to adult myocardium may have therapeutic
      implications for cardiac transplantation. We investigated the feasibility of
      adenovirus-mediated transfer of marker genes LacZ and Luciferase, as well as the
      potentially therapeutic gene of the human beta2-adrenergic receptor in a rat
      heterotopic heart transplant model. METHODS: Donor hearts were flushed with
      10(12) total viral particles of one of three transgenes. Hearts were harvested at
      various time points after transplantation. LacZ-treated hearts were assessed by
      histologic staining and Luciferase-treated hearts were assayed for specific
      luminescence activity. Hearts treated with beta2-adrenergic receptor underwent
      radioligand binding assays and immunohistochemistry with the use of an antibody
      specific for the human beta2-adrenergic receptor. RESULTS: LacZ hearts revealed
      diffuse myocyte staining as opposed to none within controls at 5 days. Luciferase
      hearts demonstrated a mean activity of 970,000 +/- 220,000 arbitrary light units
      versus 500 +/- 200 for the controls (p = 0.001). Total beta2-adrenergic receptor
      densities (fmol/mg membrane protein) for hearts that received the beta2
      adrenergic receptor transgene at 3, 5, 7, 10, and 14 days after infection were as
      follows: right ventricle, 488.5 +/- 126.8, 519.4 +/- 81.8,* 477.1 +/- 51.8,*
      183.0 +/- 6.5,* and 82.7 +/- 19.1; left ventricle, 511.0 +/- 167.6, 1206.4 +/-
      321.8,* 525.3 +/- 188.7, 183.5 +/- 18.6,* and 75.9 +/- 15.2 (*p < 0.05 vs control
      value of 75.6 +/- 6.4). Immunohistochemical analysis revealed diffuse staining of
      varying intensity within myocardial sarcolemmal membranes. CONCLUSIONS: We
      conclude that global overexpression of different transgenes is possible during
      cardiac transplantation and, ultimately, adenovirus-mediated gene transfer may
      provide a unique opportunity for genetic manipulation of the donor organ,
      potentially enhancing its function.

PMID- 9535451
TI  - Addition of a mast cell stabilizing compound to organ preservation solutions
      decreases lung reperfusion injury.
AB  - OBJECTIVE: Research in lung transplant preservation has generally focused on free
      radicals and enzyme release from neutrophils, parenchymal cells, macrophages, and
      endothelium. The lung has a large resident population of mast cells that, when
      activated, release potent inflammatory mediators. We hypothesized that adding an
      inhibitor of mast cell degranulation, lodoxamide tromethamine (10 micromol/L), to
      Euro-Collins and University of Wisconsin preservation solutions, would decrease
      lung preservation injury. METHODS: Rat lungs were isolated, flushed with the
      respective solution, and stored at 4 degrees C for 6 or 12 hours. The lungs were
      reperfused with fresh blood and ventilated with 100% oxygen. Alveolar-arterial
      oxygen difference, oxygen tension, capillary filtration coefficient, and
      compliance were determined. RESULTS: After 6 hours of ischemic storage:
      lodoxamide tromethamine-enhanced Euro-Collins solution decreased alveolar
      arterial oxygen difference from 539 to 457 (p = 0.004), increased oxygen tension
      from 119 to 205 mm Hg (p = 0.006), and decreased capillary filtration coefficient
      from 3.9 to 2.0 (p < 0.001); lodoxamide tromethamine-enhanced University of
      Wisconsin solution decreased alveolar-arterial oxygen difference from 546 to 317
      (p < 0.001), increased oxygen tension from 166 to 335 mm Hg (p < 0.001), and
      decreased capillary filtration coefficient from 3.0 to 1.7 (p < 0.001). After 12
      hours of ischemic storage, lodoxamide tromethamine-enhanced Euro-Collins solution
      decreased alveolar-arterial oxygen difference from 588 to 485 (p < 0.001),
      increased oxygen tension from 100 to 161 mm Hg (p = 0.012), decreased capillary
      filtration coefficient from 6.2 to 2.6 (p < 0.001), and increased compliance from
      0.12 to 0.21 (p < 0.001); lodoxamide tromethamine-enhanced University of
      Wisconsin solution decreased alveolar-arterial oxygen difference from 478 to 322
      (p < 0.001), increased oxygen tension from 214 to 335 mm Hg (p < 0.001),
      decreased capillary filtration constant from 4.2 to 2.0 (p < 0.001), and
      increased compliance from 0.20 to 0.25 (p < 0.001). CONCLUSIONS: Addition of
      lodoxamide tromethamine to Euro-Collins or University of Wisconsin solution
      results in a marked decrease in lung reperfusion injury as demonstrated by
      increased oxygenation, decreased microvascular permeability, and increased
      compliance. These results are relevant as Euro-Collins and University of
      Wisconsin solutions are the most common clinically used lung preservation
      solutions. This study also highlights the deleterious role of resident mast cells
      in preservation injury.

PMID- 9535452
TI  - Gene therapy in lung transplantation: effective gene transfer via the airways.
AB  - OBJECTIVES: Gene therapy may provide a means of modifying factors that contribute
      to the development of pathologic processes in transplanted lungs. Experiments
      were designed to study the feasibility of adenovirus-mediated gene transfer by
      way of the airways to the transplanted lung. METHODS: Orthotopic left lung
      transplantation (Lewis to Lewis rats) was performed on four groups of animals.
      300 microl of adenovirus solution encoding for beta-galactosidase was infused
      into the left bronchus of donor rats at viral concentrations of 10(8) pfu/ml (n =
      5), 10(9) pfu/ml (n = 6), and 10(10) pfu/ml (n = 6), and the lung was ventilated
      for 5 minutes. Controls (n = 6) received medium only. Seven days after
      transplantation, native and transduced, transplanted lungs were harvested.
      Sections of lung were fixed and stained with a solution of X-Gal (5-bromo-4
      chloro-3-indolyl-beta-D-galactopyranoside) and staining was evaluated for
      distribution by cell type and intensity. RESULTS: Beta-galactosidase expression
      was absent in the control group and in the native lungs. Two of five lungs in the
      10(8) group expressed beta-galactosidase, but in a limited distribution and
      intensity. All six lungs in the 10(9) group and five of six lungs in the 10(10)
      group expressed beta-galactosidase. The distribution and intensity of beta
      galactosidase expression ranged from only a few cells staining per slide to up to
      75%. Pneumocytes were the most frequently stained cell type followed by alveolar
      macrophages. CONCLUSIONS: Gene transfer to the transplanted lung via the
      bronchial route is feasible and offers a novel technique to modify pathologic
      processes in the transplanted lung.

PMID- 9535453
TI  - Lung growth after transplantation of an adult lobe of lung into a juvenile rat.
AB  - OBJECTIVE: Shortage of donor organs for children has led to the use of living
      related adult lung lobar transplants. It is not known how these lobes or the
      recipient remaining lung grow after such transplants. The purpose of the present
      study was to assess lung growth in rat lungs up to 6 months after adult lobe
      transplantation into a juvenile recipient. METHODS: Right cardiac lung lobes from
      adult male Lewis rats were transplanted into the left hemithorax of juvenile (6
      week-old) male Lewis rats after left pneumonectomy. Animals with appropriate
      controls were put to death 14 days and 6 months after transplantation. The lungs
      were fixed inflated and studied by means of quantitative morphometric techniques.
      RESULTS: By 6 months after transplantation both the recipient right lung and the
      transplanted cardiac lobe were significantly larger than normal (p = 0.005; p =
      0.001). In the recipient right lung this increase was due to an increase in the
      number of alveoli (p = 0.004) and in the transplanted cardiac lobe to an increase
      in size of the alveoli (p = 0.008). CONCLUSIONS: An adult lobe transplanted into
      a young recipient is still viable and has normal architecture after 6 months, and
      growth of the recipients' own lung continues. The outlook for comparable
      transplants in children is promising, although the human condition can be
      complicated by rejection, infection, and treatment strategies.

PMID- 9535454
TI  - Angiogenesis as a predictor of survival after surgical resection for stage I non
      small-cell lung cancer.
AB  - OBJECTIVES: Some patients with surgically resected stage I non-small-cell lung
      cancer eventually have metastatic disease. A histologic marker of metastatic
      potential and diminished survival for stage I non-small-cell lung cancer may
      distinguish this patient population. This study evaluates the degree of
      angiogenesis as a predictor of cancer-related death after operation for stage I
      non-small-cell lung cancer. METHODS: Demographic, surgical, and histopathologic
      data, including presence of vascular invasion, were reviewed for 106 patients
      with stage I non-small-cell lung cancer from 1985 through 1990. Visual
      quantitation of microvessels immunostained with factor VIII-related antigen and
      CD31 in 5 microm sections from the paraffin blocks of tissue defined rumor
      angiogenesis. RESULTS: Follow-up was 95.1% complete, mean 5.2 +/- 3.0 years. Lung
      cancer-related mortality rate was 24.4% at 5 years. Mean microvessel counts were
      20.7 +/- 11.2 for FVIII and 29.6 +/- 18.1 for CD31. Univariate analysis revealed
      an FVIII count of at least 20 (p = 0.025) and blood vessel invasion (p = 0.017)
      to be significant predictors of disease-related death. After adjustment for other
      patient and tumor characteristics, multivariate Cox regression analysis found an
      FVIII count of at least 20 (hazard ratio 2.9) and blood vessel invasion (hazard
      ratio 3.7) to be significant independent correlates of lung cancer death (p =
      0.018 and p = 0.011, respectively). CD31 quantitation did not predict survival on
      univariate or multivariate analyses and did not correlate strongly with FVIII
      quantitation (Spearman's rank correlation r = 0.19). CONCLUSIONS: This analysis
      reveals a significant association between tumor neovascularization and cancer
      related mortality rate among patients with stage I non-small-cell lung cancer.
      Microvessel quantitation of FVIII, as an indicator of tumor angiogenesis and
      metastatic potential, may define a subset of patients with stage I non-small-cell
      lung cancer who could benefit from adjuvant therapy after surgical resection.

PMID- 9535455
TI  - Proposed revision of the staging classification for esophageal cancer.
AB  - OBJECTIVES: This study analyzed survival with respect to lymph node involvement
      to develop a new staging system for patients with esophageal cancer that
      accurately reflects prognosis. METHODS: The records of patients undergoing
      resection of primary esophageal cancer from 1989 to 1993 were reviewed. The data
      collected included patient age and sex, tumor histologic characteristics and
      location, the use of preoperative or postoperative radiation and chemotherapy,
      the type of resection, the depth of tumor invasion, the number and location of
      benign and malignant lymph nodes in the resected specimen, the disease status at
      last follow-up, and the first site of relapse. With an anatomically specific
      lymph node map, tumors designated in the current American Joint Committee on
      Cancer system as M1 because of extensive lymph node metastases were reclassified
      as N2, reserving the M1 category for visceral metastases. Survival was analyzed
      by the Kaplan-Meier method, and prognostic factors were assessed by log-rank and
      Cox regression analyses. RESULTS: There were 216 patients (159 men, 57 women)
      with a median age of 63.5 years. Adenocarcinoma of the distal esophagus or
      gastroesophageal junction was the most common tumor (127 patients, 59%) and Ivor
      Lewis esophagogastrectomy was the most frequently performed operation. Both lymph
      node location (N1 versus N2) and number (0 vs 1 to 3 vs 4 or more) significantly
      influenced survival. CONCLUSIONS: A new staging system that adds an N2 M0
      descriptor and reclassifies stage groupings reflects prognosis more accurately
      than does the current American Joint Committee on Cancer staging system. The
      number of positive lymph nodes is also an important stratification factor.

PMID- 9535456
TI  - Primary sarcomas of the mediastinum: results of therapy.
AB  - Primary sarcomas of the mediastinum are rare, and data concerning treatment and
      results of therapy are sparse. OBJECTIVE: To assess presentation, management,
      prognostic factors, and survival in mediastinal sarcomas. METHODS: We reviewed
      our experience with 47 patients with the diagnosis of primary sarcoma of the
      mediastinum. Data were collected from a computerized institutional database and
      medical records. Survival was analyzed by Kaplan-Meier method and comparisons of
      survival by log rank test. RESULTS: The median age of 47 patients with
      mediastinal sarcoma was 39 years (range 2.5 to 69 years), with a male/female
      ratio of 1.6. The most common complaints were chest/shoulder pain (38%) and
      dyspnea (23%). The most common tumor types were malignant peripheral nerve tumor
      (26%), spindle cell sarcoma (15%), leiomyosarcoma (9%), and liposarcoma (9%).
      Operation was the primary treatment modality in 72% of cases (n = 34); 22
      sarcomas (47%) were completely resected. The overall 5-year survival was 32%.
      High-grade lesions had a significantly decreased survival (5-year survival = 27%)
      compared with low-grade tumors (5-year survival = 66%) (p = 0.05). The
      overwhelming factor determining survival was the ability to completely resect the
      tumors (5-year survival 49% for complete resection; 3-year survival 18% for
      incomplete or no resection) (p = 0.0016). Despite complete resection, local
      recurrence occurred in 64% of cases. CONCLUSION: Because the overall survival for
      patients with mediastinal sarcomas is 32% and the local recurrence is 64% for
      tumors completely resected, aggressive adjuvant therapy should continue to be
      systematically explored.

PMID- 9535457
TI  - Lobectomy combined with volume reduction for patients with lung cancer and
      advanced emphysema.
AB  - OBJECTIVE: Early-stage lung cancer is best treated by anatomic pulmonary
      resection. Patients with lung cancer and severe emphysema are often denied
      resection or are offered only limited, nonanatomic resections when established
      pulmonary function criteria for lobectomy are not met. Recently, with the
      introduction of the volume reduction operation, selected patients with disabling
      emphysema have undergone excision of approximately 30% of the most destroyed lung
      tissue and have subsequently demonstrated subjective and objective improvement in
      pulmonary function. Using these principles, we elected to combine anatomic
      lobectomy with volume reduction in a select group of patients with both emphysema
      and lung cancer who would not otherwise be candidates for pulmonary resection.
      METHODS: Five patients with severe emphysema and suspected or proven lung
      cancers, who were poor candidates for anatomic lobectomy by traditional criteria
      but were good candidates for volume reduction, underwent lobectomy combined with
      volume reduction of one or more additional lobes. RESULTS: All five patients
      having lung volume reduction and anatomic lobectomy for early-stage primary lung
      cancer did well postoperatively. Furthermore, each patient has demonstrated
      subjective and objective improvement in respiratory function on serial
      postoperative studies. CONCLUSIONS: Selected patients with disabling emphysema
      and suitable anatomy for volume reduction, who have a lung cancer situated in
      destroyed lung tissue, may benefit from combined lobectomy and volume reduction.
      The introduction of the volume reduction operation has added a new factor in the
      algorithm for the evaluation and treatment of lung cancer in selected patients
      with advanced emphysema.

PMID- 9535458
TI  - Intercellular adhesion molecule-1 regulation in the canine lung after
      cardiopulmonary bypass.
AB  - OBJECTIVE(S): Neutrophil sequestration in the lung after cardiopulmonary bypass
      has been shown to be dependent on the adhesion molecule CD18. Thus we sought to
      determine whether endothelial expression of intercellular adhesion molecule-1 (a
      ligand for CD18) in pulmonary capillaries mediates neutrophil adhesion in this
      setting. METHODS: Seven adult mongrel dogs underwent 90 minutes of hypothermic
      cardiopulmonary bypass with 60 minutes of cardioplegic arrest. After warming,
      dogs were reperfused for up to 9 hours and lung biopsy specimens were obtained.
      Lung tissue was examined by Northern and Western blot analysis and by
      immunohistologic methods. Three sham-operated dogs served as time-matched
      controls. RESULTS: Northern blots demonstrated increased expression of
      intercellular adhesion molecule-1 messenger ribonucleic acid within 5 minutes of
      cessation of bypass (or approximately 30 minutes after aortic crossclamp
      release), which persisted at 9 hours of recovery and was not present in controls.
      Western blots showed intercellular adhesion molecule-1 protein expression before
      bypass but a measurable increase in intercellular adhesion molecule-1 protein in
      four of seven dogs in the bypass group by the ninth hour of recovery. Pulmonary
      neutrophil accumulation 9 hours after cardiopulmonary bypass was greater in those
      dogs with an increased intercellular adhesion molecule-1 protein expression.
      Immunoelectron microscopy demonstrated the pulmonary capillary endothelium
      capable of increased intercellular adhesion molecule-1 protein expression at the
      9-hour time point. CONCLUSIONS: Cardiopulmonary bypass resulted in intercellular
      adhesion molecule-1 induction in the canine lung during recovery. An increased
      expression of intercellular adhesion molecule-1 protein in the lung was
      associated with an increased accumulation of neutrophils in affected animals.
      Thus intercellular adhesion molecule-1 expression may serve as a mechanism that
      predisposes the lungs to inflammatory cell-mediated injury postoperatively.

PMID- 9535459
TI  - Inhaled nitric oxide is not a myocardial depressant in a porcine model of heart
      failure.
AB  - BACKGROUND: Inhaled nitric oxide has been shown to be a potent and selective
      pulmonary vasodilator. Reports of increases in left ventricular end-diastolic
      pressure and episodes of pulmonary edema during the clinical use of inhaled
      nitric oxide in patients with preexisting left ventricular dysfunction have
      raised concerns that this agent may have myocardial depressant effects. We
      therefore undertook a study of the effects of inhaled nitric oxide on myocardial
      contractility in a porcine model of ventricular failure and pulmonary
      hypertension. METHODS: After inducing heart failure in 10 pigs by rapid
      ventricular pacing, hemodynamic measurements and pressure-volume diagrams (by the
      conductance method) were obtained in six animals at baseline and during
      administration of inhaled nitric oxide at concentrations of 20 and 40 ppm.
      Myocardial contractile state was assessed by the end-systolic pressure-volume
      relationship and preload-recruitable stroke work, whereas diastolic function was
      measured in terms of the end-diastolic pressure-volume relationship and the
      pressure decay time constant T. RESULTS: Baseline hemodynamics reflected heart
      failure and pulmonary hypertension, and inhaled nitric oxide induced significant
      reductions in mean pulmonary artery pressure and pulmonary vascular resistance.
      Although left ventricular end-diastolic pressure increased during administration
      of inhaled nitric oxide, no changes were observed in measures of systolic or
      diastolic function. CONCLUSIONS: Inhaled nitric oxide reduced pulmonary vascular
      resistance but did not alter myocardial contractility or diastolic function.
      Increases in left ventricular end-diastolic pressure during inhaled nitric oxide
      therapy are therefore not due to myocardial depression and may be related to
      increases in volume delivery to the left side of the heart resulting from reduced
      pulmonary vascular resistance.

PMID- 9535460
TI  - Sodium/hydrogen exchanger inhibition reduces myocardial reperfusion edema after
      normothermic cardioplegia.
AB  - OBJECTIVE: The hypothesis was that Na+/H+ exchange occurring during normothermic
      cardioplegia contributes to the development of myocardial edema during subsequent
      reperfusion and impairs functional recovery. METHODS: Rat hearts were perfused in
      a Langendorff apparatus and submitted to 60 minutes of normothermic cardioplegia
      and 90 minutes of reperfusion. Hearts were allocated to one of four groups (n =
      8): inhibition of Na+/H+ exchanger with HOE642 throughout the whole experiment
      (HOE group), only during cardioplegia (HOE-C) or during reperfusion (HOE-R), and
      a control group. RESULTS: In HOE and HOE-C groups, myocardial water content at
      the end of reperfusion was lower than in the HOE-R and control groups (526 +/- 19
      and 533 +/- 18 ml/100 gm dry tissue vs 632 +/- 25 and 634 +/- 17 ml/100 gm dry
      tissue, respectively, p = 0.001), left ventricular end-diastolic pressure
      increased less after reperfusion (46.6 +/- 9.7 and 63.2 +/- 10.0 mm Hg vs 75.1 +/
      4.3 mm Hg and 85.7 +/- 8.9 mm Hg, respectively, p = 0.006), and recovery of left
      ventricular developed pressure was better (46.7% and 45.8% vs 4.5% and 9.8%, p =
      0.048). Relative to the control group, total lactate dehydrogenase release during
      reperfusion was reduced by 80.2%, 69.3% and 36% in HOE, HOE-C, and HOE-R groups,
      respectively. CONCLUSION: Inhibition of the Na+/H+ exchange during normothermic
      cardioplegia reduces myocardial edema and necrosis during subsequent reperfusion,
      improving functional recovery. Inhibition of Na+/H+ exchange during reperfusion
      only has a much smaller effect.

PMID- 9535461
TI  - Simultaneous antegrade and retrograde delivery of continuous warm blood
      cardioplegia after global ischemia.
AB  - OBJECTIVE: Simultaneous delivery of antegrade and retrograde cardioplegia may
      provide a more homogeneous distribution of cardioplegic solution. It may,
      however, increase myocardial edema and postcardioplegic myocardial injury. The
      purpose of this study was to compare simultaneous antegrade-retrograde
      cardioplegia with antegrade cardioplegia. METHODS: After 30 minutes of warm,
      "unprotected," global ischemia, pigs were given warm, continuous blood
      cardioplegia for 45 minutes (antegrade group, n = 8 and simultaneous antegrade
      retrograde group, n = 9). All pigs were weaned from cardiopulmonary bypass 45 to
      60 minutes after aortic unclamping. Indices of left ventricular function were
      measured after another 30 minutes with the conductance catheter technique and
      pressure-volume loops. RESULTS: Global left ventricular function, evaluated by
      preload recruitable stroke work, decreased from baseline values of 126 (102 to
      150) (mean [90% confidence limits]) (antegrade) and 122 (116 to 127) erg/ml x
      10(3) (simultaneous) to 75 (61 to 89) (p = 0.004) and 95 (79 to 112) erg/ml x
      10(3) (p = 0.02), respectively. End-diastolic pressure-volume relation increased
      from 0.25 (0.21 to 0.28) (antegrade) and 0.30 (0.25 to 0.35) mm Hg/ml
      (simultaneous) to 0.60 (0.41 to 0.79) (p = 0.009) and 0.53 (0.35 to 0.71) mm
      Hg/ml (p = 0.02), respectively. The time constant of left ventricular pressure
      relaxation was unchanged. No intergroup difference was observed in preload
      recruitable stroke work, preload recruitable stroke work area, end-diastolic
      pressure volume relation, or stiffness constant. Plasma levels of troponin T
      increased without any difference between groups. Myocardial water content was
      increased in the simultaneous group (81.1% [80.7% to 81.5%]) versus the antegrade
      group (80.1% [79.6% to 80.7%], p = 0.01). CONCLUSION: Despite a small increase in
      myocardial water content induced by simultaneous blood cardioplegia, no
      impairment of postcardioplegic cardiac function was observed compared with
      antegrade cardioplegia.

PMID- 9535462
TI  - Fatal intraoperative pulmonary thrombosis after graft replacement of an aneurysm
      of the arch and descending aorta in association with deep hypothermic circulatory
      arrest and aprotinin therapy.

PMID- 9535463
TI  - Concentric left ventricular hypertrophy late after aortic valve replacement in
      Takayasu's arteritis.

PMID- 9535464
TI  - Massive pericardial hematoma simulating constrictive pericarditis: a complication
      of radiofrequency catheter ablation.

PMID- 9535465
TI  - Mitral regurgitation late after Manouguian's anulus enlargement and aortic valve
      replacement.

PMID- 9535466
TI  - Application of a heparin removal device in patients with known protamine
      hypersensitivity.

PMID- 9535467
TI  - Coagulation abnormalities after Fontan procedures.

PMID- 9535468
TI  - New valid technique for ventricular septal defect associated with aortic
      regurgitation.

PMID- 9535469
TI  - Thoracic duct ligation for chylopericardium.

PMID- 9535470
TI  - I, too, can top this.

PMID- 9535471
TI  - We did top this!

PMID- 9535472
TI  - Relationships between myocardial activity and potentials on the ventricular
      surfaces.

PMID- 9535473
TI  - Electrical mapping in combination with intracardiac ultrasound for electrical
      anatomic correlation.

PMID- 9535474
TI  - Optical mapping of cardiac electrical stimulation.
AB  - Optical mapping has been used to determine changes in transmembrane voltage
      during electrical stimulation pulses (deltaVm) and whether deltaVm depends on
      fiber orientation, as predicted from bidomain models. Fiber orientation in an
      approximately 1 cm2 mm mapped region on the rabbit left or right ventricular
      epicardium was estimated optically from the fast axis of action potential (AP)
      propagation. Hearts were paced outside of the region to produce APs. Unipolar
      stimulation (S2) was then applied early in the AP, when tissue was refractory, so
      that deltaVm was not obscured by a new AP. Anodal S2 produced negative deltaVm
      near a point S2 electrode and away from it in the direction perpendicular to the
      fibers. Anodal S2 produced reversal of the sign of deltaVm about 1 mm from the
      electrode in the direction parallel to the fibers, such that a positive deltaVm
      existed about 1-5 mm away from the electrode. Reversal of the sign of deltaVm in
      the direction parallel to the fibers also occurred with cathodal S2, which
      produced a negative deltaVm away from the electrode parallel to the fibers. The
      results indicate a "dogbone" pattern of deltaVm, as predicted from bidomain
      models that have resistance anisotropy ratios of trabecular muscles (ie, an
      intracellular ratio that does not equal the extracellular ratio). Thus, optical
      mapping can indicate fiber orientation and deltaVm, and the deltaVm during
      unipolar stimulation reverses sign on the axis parallel to the fibers, which
      differs from one-dimensional model predictions. The deltaVm agrees with
      multidimensional bidomain model predictions that have unequal resistance
      anisotropy.

PMID- 9535475
TI  - Noninvasive imaging and catheter imaging of potentials, electrograms, and
      isochrones on the ventricular surfaces.

PMID- 9535476
TI  - Atrial cardiac memory: fact or fiction?

PMID- 9535477
TI  - Prospective evaluation of a microprocessor-assisted cardiac rhythm algorithm:
      results from one clinical center.
AB  - A new microprocessor-assisted cardiac rhythm algorithm (MAC-RHYTHM), based on
      median QRST subtraction from 10-second electrocardiographic (ECG) data, was
      prospectively tested on 10,761 ECGs acquired at one of three clinical centers.
      Atrial waves (P waves, atrial fibrillatory waves, and flutter waves) were
      detected from the median QRST-subtracted residual signals. Rhythm criteria were
      applied to the detected atrial waves and their temporal relation to QRS complexes
      for generating rhythm interpretations. Rhythm statements generated by MAC-RHYTHM
      were compared against the true rhythm of the ECGs as read by an experienced
      cardiologist. The results of prospective testing were compared with the results
      of an earlier retrospective testing using MAC-RHYTHM and a released commercial
      ECG analysis program on stored ECGs. The prospective results were very similar to
      the results of MAC-RHYTHM on retrospective data for all the rhythms examined
      (sinus rhythms, atrial fibrillation, atrial flutter, junctional rhythms, second
      degree atrioventricular blocks). For three of the abnormal rhythms, namely,
      atrial fibrillation, junctional rhythms, and second degree atrioventricular
      blocks, MAC-RHYTHM gave significantly higher sensitivity in both prospective
      (87.5%, 92.2%, and 80.8%, respectively) and retrospective (82.0%, 81.2%, and
      79.6% respectively) testing than the released commercial ECG analysis program
      (65.0%, 39.6%, and 12.0% respectively). Similarly, for sinus rhythms, MAC-RHYTHM
      had significantly higher specificity (prospective, 91.0% and retrospective,
      91.7%) than the released commercial program (86.5%). The specificity for the
      abnormal rhythms remained very high with MAC-RHYTHM (prospective, 99.4% to 99.7%
      and retrospective, 99.1% to 99.7%) compared to the released commercial program
      (99.0% to 99.9%). This prospective study also indicated that further work is
      needed to improve the detection of pacemaker spikes and the interpretation of
      paced rhythms in 10-second resting ECGs.

PMID- 9535478
TI  - Sex-specific differences in the P wave signal-averaged ECG. Multicenter P HiRes
      Study.

PMID- 9535479
TI  - Value of the signal-averaged P wave analysis in predicting atrial fibrillation
      after cardiac surgery.
AB  - Atrial fibrillation (AF) is the most common sustained arrhythmia occurring after
      cardiac surgery. Beside important implications regarding patient recovery, AF has
      been shown to substantially lengthen hospital stay--our recent study found a 3
      day prolongation after adjusting for all other significant factors.
      Identification of those at highest risk of AF by clinical or noninvasive
      characteristics may be a useful strategy for targeted prophylactic therapy. Our
      data have shown that prolonged atrial conduction as assessed by analysis of the P
      wave duration from the signal-averaged electrocardiogram (SAECG) imparts a four
      fold increase in risk for postoperative AF, independently of other measured
      variables. In addition, abnormal conduction was present on the preoperative P
      wave ECG (P-SAECG), implying a preexisting substrate that is triggered by
      surgery. The use of combination abnormal noninvasive variables (eg, abnormal P
      SAECG and low left ventricular ejection fraction) can identify groups with a 50%
      risk of AF, which is nine times as high as when both tests are normal. Thus, the
      P-SAECG is a useful and accurate predictor of AF after cardiac surgery.

PMID- 9535480
TI  - New and neglected aspects of atrial depolarization and repolarization.

PMID- 9535481
TI  - Reflex and mechanical aspects of cardiovascular development: techniques for
      assessment and implications.

PMID- 9535482
TI  - Heritability of ECG measurements in adult male twins.
AB  - To assess the genetic contribution to electrocardiographic (ECG) measurements,
      heritability analysis was performed on ECG data collected on 251 pairs of adult
      male twins during the second examination of the National Heart, Lung and Blood
      Institute twin study, a multicenter study of cardiovascular risk factors. Resting
      12-lead ECGs were obtained on each twin, pair and, the R-R, QRS, QT, and JT
      intervals were measured. Both the R-R and QT intervals demonstrated significant
      heritable components, accounting for 77% and 36%, respectively, of the
      variability. No significant heritable component of the QRS complex could be
      identified. Although the MZ intraclass correlation was higher than the DZ
      intraclass correlation, the JT interval did not demonstrate significant
      heritability. Therefore, in adult males both heart rate and the duration of
      ventricular repolarization have significant heritable components. These heritable
      components may need to be considered when using ECG measurements to screen for
      patients at risk for cardiovascular disorders or sudden cardiac death.

PMID- 9535483
TI  - Investigative methods of congenital complete heart block.
AB  - Congenital heart block (CHB) has been described for a century and related to the
      presence of maternal autoimmune disease for three decades, but little is
      understood about its mechanism. To explore the pathophysiology of CHB,
      technologies in both basic and clinical electrophysiology are being developed and
      applied. Human fetal rhythm is currently inferred from cardiac mechanical events
      by using fetal ultrasound, allowing for the detection of second and third-degree
      heart block. Fetal electrocardiography is being explored to assess its
      feasibility as a clinical tool to detect fetal first-degree block in the mid
      trimester. Sequential composite digital recordings from the maternal abdomen are
      made every 4 weeks from pregnancies at risk for congenital heart block. Filtering
      and averaging techniques are used to enhance the fetal signal. So far, these
      techniques have produced a fetal QRS complex trigger signal for use in three
      dimensional fetal echocardiography. Because the human fetus cannot be studied
      directly, a Langendorff rabbit model of CHB has been developed. With 5-10 mL of
      human serum in 150-300 mL of Krebs solution, prolongation of the Wenckebach
      second-degree atrioventricular block cycle length occurred. This was reproduced
      by using serum from seven of eight CHB mothers as compared with none of six
      controls mothers.

PMID- 9535484
TI  - Electrical-anatomic correlations between typical atrial flutter and intra-atrial
      re-entry following atrial surgery.
AB  - It is well known that in typical (or type I) atrial flutter, conduction proceeds
      counterclockwise, up the interatrial septum and down the right atrial wall
      anterior to the crista terminalis (CT). Recent careful mapping studies using
      entrainment pacing have clearly shown the importance of the CT and the eustachian
      valve ridge (EVR), which act as fixed barriers to intra-atrial conduction and
      interact with other barriers, including the tricuspid valve, inferior vena cava
      (IVC), and coronary sinus os, to create a long macroreentrant circuit. Ablative
      lesions are directed at the isthmus between the tricuspid valve and the IVC or
      between the tricuspid valve and the EVR. Patients who have had cardiac surgery
      may have typical atrial flutter, either counterclockwise or clockwise, and prior
      surgery may act to stabilize the circuit. Such patients may also have atypical
      flutter, which does not utilize this circuit. Surgical closure of septal defects
      requires a long anterior oblique atriotomy. Commonly, reentrant circuits are
      identified that use this barrier, as well as the tricuspid valve and CT, and are
      confined to the anterior atrial wall and do not involve the typical flutter
      isthmus. These may be ablated at the lower or the upper end of the atriotomy,
      extending the block to the tricuspid valve, IVC, or superior vena cava. After the
      Senning or Mustard procedure, typical flutter is common, and the baffle bisects
      the isthmus at the site of the EVR, perhaps enforcing block. Anterior atriotomy
      mediated reentry also is seen, and both circuits need to be approached in a
      retrograde manner. After the Fontan atriopulmonary connection, atriotomies and
      atrial dilation may interact to make reentry more likely. After the "lateral
      tunnel" Fontan (cavopulmonary connection) suture lines are similar to those of
      the Senning procedure, but nearly all right atrial anatomy is in the pulmonary
      venous atrium. Such circuits may need to be approached via an atrial
      fenestration.

PMID- 9535485
TI  - A canine model of atrial flutter following the intra-atrial lateral tunnel Fontan
      operation.
AB  - Atrial flutter (AFL) is a common problem in children who have undergone a Fontan
      operation for single ventricle physiology. Although this has been attributed to
      the atrial stretch inherent in the earlier forms of this operation, AFL has
      persisted in spite of a modification that minimizes atrial distension. Therefore,
      it was hypothesized that AFL following the modified Fontan procedure may result
      from anatomic barriers related to suture lines rather than from atrial stretch or
      hypertension. In a series of experiments performed in dogs under general
      anesthesia, the modified Fontan repair was simulated by placing only the suture
      line of the intra-atrial repair. No baffle was placed, thus avoiding any
      hemodynamic alterations. After closure of the atriotomy, 253 point unipolar
      atrial endocardial form-fitting electrodes were inserted through the mitral and
      tricuspid valves via bilateral ventriculotomies. Induction of AFL was attempted
      with atrial burst pacing and programmed extrastimulation, and activation sequence
      maps of subsequent reentry were generated from the endocardial electrodes. Atrial
      flutter was induced in all of 17 dogs, with a median cycle length of 177 +/- 31
      ms. Activation sequence maps demonstrated conduction block along the crista
      terminalis corresponding to the free wall portion of the suture line. This
      created an isthmus between the suture line and tricuspid annulus, which appeared
      critical for sustaining AFL, although the circuit used both the septal and free
      wall surfaces of the right atrium. In seven dogs, a cryolesion was placed from
      the tricuspid annulus to the free wall segment of the suture line, terminating
      the AFL, in all seven. When the free wall segment of the suture line was moved 5
      mm medial to the crista terminalis, AFL was induced in four of five dogs, but
      only in the presence of isoproterenol and at a shorter cycle length (136 +/- 8
      ms, P < .001). Atrial flutter was not inducible, even with the addition of
      isoproterenol, in any of five dogs in which the suture line was placed 10 mm
      anterior to the crista terminalis and incorporated into closure of the atriotomy.
      This acute canine model of the modified Fontan operation demonstrates that
      conduction block from the free wall portion of the suture line creates an isthmus
      of tissue between the suture line and the tricuspid annulus. This is a sufficient
      substrate to produce AFL; no hemodynamic alteration is required. Injury to the
      crista terminalis is a significant risk factor in this model, which suggests that
      a modification of the suture line might reduce the incidence of AFL in patients
      following this operation.

PMID- 9535486
TI  - Possible mechanism of ECG features in patients with idiopathic ventricular
      fibrillation studied by heart model and computer simulation.
AB  - The possible contribution of localized conduction delay and abnormal action
      potentials to ventricular fibrillation (VF) was studied by applying an
      anisotropic cardiac computer model to clinical cases of the Brugada-type
      electrocardiogram (ECG), which shows right bundle branch block (RBBB), a normal
      QT interval, ST-segment elevation, and late r' in leads V1 and V2. The
      anisotropic heart model was composed of 50,000 discrete units with a spatial
      resolution of 1.5 mm and was mounted in a human torso model. The
      longitudinal/transverse conduction velocity ratio was 3:1. For the normal ECG, a
      conduction velocity of 0.75 m/s was required. In the abnormal area of the right
      anterior epicardial wall, the conduction velocity was set at 0.2 m/s, with
      decreasing action potential amplitude and 10% prolonged action potential
      duration. The ECG features of ST-segment elevation and Brugada-type right bundle
      branch block pattern were simulated. The action potential duration was able to
      change dynamically with coupling interval of stimulation, with a ratio of 9% for
      normal ventricular muscle and 50% for Purkinje fibers. Five successive stimuli
      were applied to the left lateral epicardium 300 ms after the first sinus
      excitation, and sustained VF was induced with the transmural conduction delay at
      the right anterior ventricle as a block increasing the vulnerability. At the
      initiation of VF, reentry circuits were shown around the border zone of the right
      epicardium and were very heterogeneous around the conduction delayed area and
      septal area. In an area with the characteristics of nontransmural conduction
      delay, sustained VF was prevented, and the pattern of transient right bundle
      branch block appeared on the simulated ECG and body surface potential maps. The
      late r' wave was calculated in the precordial leads and right anterior site on
      the body surface potential maps. These results suggest that increased
      multipolarity in the border zone between the Purkinje fibers and delayed
      conduction area in the right ventricle might play an important role as a
      functional block for the persistence of VF.

PMID- 9535487
TI  - Magnetocardiographic turbulence analysis in patients with the long QT syndrome.

PMID- 9535488
TI  - A possible mechanism for electrocardiographically silent changes in cardiac
      repolarization.
AB  - Despite the widespread use of electrocardiogram (ECG), changes in cardiac
      activity resulting from ischemia or altered recovery characteristics sometimes
      remain electrocardiographically "silent" or are first detectable by techniques
      that measure ventricular contractility, such as ultrasound or blood pressure.
      Especially local changes in repolarization can go undetected when ECG electrodes
      do not lie close to the area of the heart affected. Experiments were performed on
      an isolated, perfused canine heart suspended in a realistically shaped,
      instrumented, electrolytic torso tank with the goal of determining some
      mechanisms for these ambiguities. By recording simultaneously both epicardial and
      torso tank surface potentials, complete descriptions were obtained of the
      electrical response to interventions such as coronary occlusions and alterations
      in pacing site and frequency. One hypothesis was that some interventions produce
      highly variable ECG responses primarily because of differences in their location
      within the heart. To test this, the effect was measured of repeating the same
      intervention as the heart's location and orientation in the tank were varied. A
      numerical forward solution was also used to investigate variation of torso tank
      potentials with heart location. The resulting changes in tank surface potentials
      illustrate how, for example, precordial ST-segment shifts following occlusion
      change from elevation to depression to become almost undetectable as the heart
      rotates in the tank. The results suggest that some events are
      electrocardiographically silent because of the complex geometric relationship of
      the heart, torso, and site of the lesion, as well as the spatial sampling and
      analysis techniques used in detection.

PMID- 9535489
TI  - A testing system for implantable cardioverter defibrillators.
AB  - Implantable cardioverter defibrillator (ICD) testing during the implantation
      process is important in order to avoid repeated induction of arrhythmias, which
      extends the implantation procedure and poses a risk to the patient. Hence, an in
      vitro testing system has been designed to assist optimal device programming and
      avoid repetitive inductions. The system includes a high-speed computer with A/D
      and D/A subsystems. Software has been designed to eliminate repeated arrhythmia
      induction by real-time capture and storage of the electrogram. Subsequently, the
      electrogram can be replayed into ICD software simulators at a variety of settings
      to determine candidate programming parameters. To validate the simulation system,
      signals were fed directly to an ICD via an attenuator. Output event markers were
      captured simultaneously with the signal into a digital file to assess the device
      performance. Four ventricular tachycardia (VT), three supraventricular
      tachycardia, (SVT), three atrial flutter (AFL), three atrial fibrillation (AF),
      and ten ventricular fibrillation (VF) passages were used to verify the system.
      Test settings were 110-160 beats/min for detection rate and 5 seconds for shock
      delay. The simulator and ICD detected the episodes for all passages at the 110
      beats/min setting. For the setting of 160 beats/min, two VTs, two SVTs, three
      AFLs, and nine VFs were detected by the device, but no Afb triggered a shock. The
      simulator detection criteria were met by two VTs, two SVTs, three AFLs, ten VFs,
      and one AF. The mean detection time was 6,869-7,330 ms (110-160 beats/min) for
      the simulator and 7,840-8,170 ms for device. Comparison of results showed general
      agreement between simulator and device. Results demonstrated that device behavior
      at a variety of settings can be elucidated by the simulator for selection of
      optimal performance. The automated system can also function as a test bed for
      evaluation of new algorithms during device development and design.

PMID- 9535490
TI  - Comprehensive scheme for detection of ventricular fibrillation for implantable
      cardioverter defibrillators.
AB  - Implantable cardioverter defibrillators (ICDs) detect and defibrillate
      ventricular fibrillation (VF) and ventricular tachycardia (VT). Other therapies
      which use less energy are also available to terminate VT. Previous studies have
      shown that ICD rate schemes often misdiagnose VT as VF. In this study, an
      improved VF classification scheme was designed and tested, which employs the
      classic rate criteria plus paired signal concordance (PSC); PSC uniquely detects
      VF where VT and VF rates overlap (220-340 ms). Two signals from a bipolar pair (1
      cm) recorded in a unipolar sense exhibit similar signal shape for concordant
      rhythms, such as sinus rhythm and VT, and disconcordance for VF. Once the rate
      criterion is met, PSC is measured by the peak normalized cross-correlation
      coefficient calculated over the depolarization. Variability, measured by a
      modified range, determined the contextual diagnosis over a passage. Sinus rhythm
      (20), VT (12), VF (22), atrial fibrillation (10), sinus rhythm with ventricular
      premature depolarizations (7), and polymorphic VT (4) passages were recorded from
      38 patients. Rate-PSC was tested with unfiltered, digitized signals (1-500 Hz,
      1,000 samples per second) and with filtered, downsampled signals (1-50 Hz, 100
      samples per second). Sensitivity values, or percentage of correct VF detection,
      and specificity values, or detection of all other rhythms, were generated and
      compared with simulations of three commercial ICDs programmed to similar settings
      as rate-PSC and to nominal settings. The sensitivity values for rate-PSC with
      unfiltered and with filtered signals and for ICDs with 220 ms and with nominal
      settings were 100%, 100%, 48-80%, and 100%, respectively; the corresponding
      specificity values were 95%, 83%, 93%, and 7-13%, respectively. It was concluded
      that the rate-PSC scheme was able to reliably separate VF from other rhythms,
      even rhythms that have a variable morphology or variable rate. With the
      confidence of accurate VF detection, use of low-energy therapies for non-VF
      rhythms will increase device longevity and enhance patient comfort.

PMID- 9535491
TI  - T wave spectral variance: A new method to determine inhomogeneous repolarization
      by T wave beat-to-beat variability in patients prone to ventricular arrhythmias.
AB  - Inhomogeneous repolarization is considered to be associated with increased risk
      of ventricular arrhythmias, but exact determination of the end of the T wave is
      difficult, and a single measurement of the QTc interval may be insufficient for
      risk stratification. A new algorithm was therefore developed to determine the
      beat-to-beat variability of the T wave in Holter electrocardiographic recordings.
      This algorithm, termed T Wave Spectral Variance (TWSV) uses the two-dimensional
      fast Fourier transform to determine the beat-to-beat variability of the T wave in
      Hotter ECG recordings. The two-dimensional fast Fourier transform was calculated
      by use of a data matrix with 1,024 consecutive single beats (first dimension) and
      a 200-ms segment centered on the T wave (second dimension). The power spectra of
      the 2D-FFT revealed the frequency content of the T wave in the first dimension
      and the periodicity of these frequencies in cycles per beat in the second
      dimension. A TWSV index of periodicity was calculated by dividing total spectral
      energy by spectral energy at 0 cycles per beat. A TWSV index of 0 means a
      constant T wave from beat to beat; a TWSV index of 1 means a completely irregular
      T wave. Of the 200 patients investigated, all of whom had had myocardial
      infarctions, 50 had documented sustained ventricular tachycardia (VT) (<230
      beats/min) (group 1), 50 had ventricular fibrillation (VF) (group 2), and 100
      were without VT or VF (group 3); 10 normal subjects were also investigated. The
      visually determined QTc was 442 +/- 62 ms in group 1, 402 +/- 13 ms in group 2,
      411 +/- 26 ms in group 3, and 398 +/- 43 ms in normal subjects (differences not
      significant). The TWSV index was 0.95 +/- 0.14 in group 1, 0.90 +/- 0.16 in group
      2, and 0.64 +/- 0.24 in group 3; it showed a highly constant T wave in normal
      subjects (0.52 +/- 0.23). Differences between patients with VT and VF as against
      patients without VT or VF were significant (P < .05), whereas no statistical
      differences between patients with VT and VF could be found. Thus, TWSV, a new
      method to assess beat-to-beat variability of the T wave, revealed increased
      heterogeneity of repolarization in patients prone to both VT and VF after
      myocardial infarction, whereas a single QTc interval measurement showed no
      significant differences.

PMID- 9535492
TI  - Wavelet transform system makes one-beat analysis possible in late potential
      evaluation.
AB  - High-frequency components of the QRS complex, including late potentials, can be
      analyzed by signal averaging (SA). However, this method may fail to detect
      transient changes as a result of cancellation. The wavelet transform, which has a
      superior time-frequency resolution, was used to analyze beat-to-beat changes of
      the QRS components in 50 normal subjects and 50 patients who showed positive late
      potentials. The transformed data, displayed in three dimensions and in color,
      were highly reproducible in each patient. Measurement of high-power duration at a
      frequency of 50 Hz (WD50) showed a significant correlation between WD50 and
      filtered QRS duration in both groups. When the mean +/- SD of WD50 in normal
      subjects was defined as normal, 96% of patients with late potentials were out of
      the normal range. The wavelet signals in patients with late potentials were more
      inhomogeneous than those of normal subjects. It is concluded that this newly
      developed color display, three-dimensional wavelet transform system showed
      extremely good time-frequency resolution in analyzing every beat without signal
      averaging.

PMID- 9535493
TI  - Device implementation, validation, and application assessment of two continuous
      12-lead ECG monitors during percutaneous transluminal coronary angioplasty:
      description of the validation method and implications for clinical trials.
AB  - Comparability of clinical and research data sets may be undermined if the
      instruments used to acquire them vary. Even when standard 12-lead
      electrocardiographic formats are used for monitoring, proprietary signal
      processing techniques and sampling intervals may differ among devices. In order
      to directly compare the two commercially available standard 12-lead devices with
      monitoring capabilities, bifurcated wires from a single standard lead set were
      attached to each device in elective angioplasty patients. Neither device was used
      as a standard; rather, a method was designed to analyze the output from each
      device independently, and then, if results differed, data from both monitors were
      reviewed by consensus to determine the source of the differences. Analysis
      endpoints for each study included study quality, baseline ST-segment levels, the
      presence of ischemia, number of ischemic episodes, peak lead location, and peak
      lead amplitude. Sources of differences in these endpoints visible to consensus
      review included variations between devices in baseline stability, noise/artifact
      levels, stability of the QRS complex onset, and temporal sampling intervals.

PMID- 9535494
TI  - Bedside diagnosis of myocardial ischemia with ST-segment monitoring technology:
      measurement issues for real-time clinical decision making and trial designs.
AB  - Monitoring of the ST segment is a valuable tool for guiding clinical decision
      making and evaluating anti-ischemia interventions in clinical trials; however,
      measurement issues hamper its diagnostic accuracy. This study reports the
      frequency and type of false positives and other measurement issues we have
      encountered during 12-lead ST-segment monitoring of patients in a cardiac care
      unit. Of 292 patients, 117 (40%) had one or more false positive events during an
      average of 41 hours of ST-segment monitoring, for a total of 506 false positive
      events. The 506 false positive events included 167 (36%) due to body positional
      change; 132 (26%) due to sudden increase in QRS complex/ST-segment voltage; 96
      (19%) due to transient arrhythmia or pacing; 80 (16%) due to heart rate change in
      steeply sloped ST-segment contours; 26 (5%) due to a noisy signal; and 5 (1%) due
      to lead misplacement. It is concluded that many conditions in addition to
      myocardial ischemia can cause transient ST-segment deviation in patients with
      unstable coronary syndromes. Accurate ST-segment monitoring requires expertise in
      electrocardiogram interpretation, an understanding of the patient's clinical
      situation, and knowledge of the functions and limitations of the ST-segment
      monitoring system.

PMID- 9535495
TI  - Cellular basis for QT dispersion.
AB  - The cellular basis for the dispersion of the QT interval recorded at the body
      surface is incompletely understood. Contributing to QT dispersion are
      heterogeneities of repolarization time in the three-dimensional structure of the
      ventricular myocardium, which are secondary to regional differences in action
      potential duration (APD) and activation time. While differences in APD occur
      along the apicobasal and anteroposterior axes in both epicardium and endocardium
      of many species, transitions are usually gradual. Recent studies have also
      demonstrated important APD gradients along the transmural axis. Because
      transmural heterogeneities in repolarization time are more abrupt than those
      recorded along the surfaces of the heart, they may represent a more onerous
      substrate for the development of arrhythmias, and their quantitation may provide
      a valuable tool for evaluation of arrhythmia risk. Our data, derived from the
      arterially perfused canine left ventricular wedge preparation, suggest that
      transmural gradients of voltage during repolarization contribute importantly to
      the inscription of the T wave. The start of the T wave is caused by a more rapid
      decline of the plateau, or phase 2 of the epicardial action potential, creating a
      voltage gradient across the wall. The gradient increases as the epicardial action
      potential continues to repolarize, reaching a maximum with full repolarization of
      epicardium; this juncture marks the peak of the T wave. The next region to
      repolarize is endocardium, giving rise to the initial descending limb of the
      upright T wave. The last region to repolarize is the M region, contributing to
      the final segment of the T wave. Full repolarization of the M region marks the
      end of the T wave. The time interval between the peak and the end of the T wave
      therefore represents the transmural dispersion of repolarization. Conditions
      known to augment QTc dispersion, including acquired long QT syndrome (class IA or
      III antiarrhythmics) lead to augmentation of transmural dispersion of
      repolarization in the wedge, due to a preferential effect of the drugs to prolong
      the M cell action potential. Antiarrhythmic agents known to diminish QTc
      dispersion, such as amiodarone, also diminish transmural dispersion of
      repolarization in the wedge by causing a preferential prolongation of APD in
      epicardium and endocardium. While exaggerated transmural heterogeneity clearly
      can provide the substrate for reentry, a precipitating event in the form of a
      premature beat that penetrates the vulnerable window is usually required to
      initiate the reentrant arrhythmia. In long QT syndrome, the trigger is thought to
      be an early afterdepolarization (EAD)-induced triggered beat. The likelihood of
      developing EADs and triggered activity is increased when repolarizing forces are
      diminished, making for a slower and more gradual repolarization of phases 2 and 3
      of the action potential, which translates into broad, low amplitude and sometimes
      bifurcated T waves in the electrocardiogram. Our findings suggest that regional
      differences in the duration of the M cell action potential may be the basis for
      QT dispersion measured at the body surface under normal and long QT conditions.
      The data indicate that the interval delimited by the peak and the end of the T
      wave represents an accurate measure of regional dispersion of repolarization
      across the ventricular wall and as such may be a valuable index for assessment of
      arrhythmic risk. The presence of low amplitude, broad and/or bifurcated T waves,
      particularly under conditions of long QT syndrome, is indicative of diminished
      repolarizing forces and may represent an independent variable of arrhythmic risk,
      forecasting the development of EAD-induced triggered beats that can precipitate
      torsade de pointes. Although the QT interval, QT dispersion, the T wave peak-to
      end interval, and the width and amplitude of the T wave often change in parallel,
      they contain different information and should not be expected to be e

PMID- 9535496
TI  - QT interval dispersion: dispersion of ventricular repolarization or dispersion of
      QT interval?
AB  - The QT interval (QTI) has long been useful as a clinical index of the duration of
      ventricular repolarization, particularly as a marker of prolonged repolarization
      and its well-established association with arrhythmogenic cardiac states.
      Likewise, inhomogeneity (dispersion) of repolarization has been linked
      definitively to increased susceptibility to reentrant arrhythmias. Recent studies
      have reported the use of QTI dispersion as a meaningful clinical index to
      identify patients at risk, but the interpretation of the measurement has been
      controversial. A Langendorff-perfused, isolated canine heart suspended in a torso
      shaped, electrolytic tank filled with NaCl-sucrose solution was used to
      investigate the relationship between body surface QTIs and ventricular
      repolarization measured directly from the cardiac surface by using activation
      recovery intervals, which have been documented to reflect the duration of local
      action potentials as well as local refractory periods. The data showed poor
      correlation between cardiac surface activation-recovery intervals and QTIs, as
      well as the insensitivity of QTIs to regional repolarization shortening in the
      presence of prolonged repolarization elsewhere. Furthermore, the data confirmed
      that torso tank QTI dispersion does not reflect directly the full range of
      measured ventricular repolarization inhomogeneity. It is concluded that body
      surface QTI dispersion is not a reliable index of repolarization dispersion.

PMID- 9535497
TI  - Algorithms for computerized QT analysis.
AB  - Several methods for measurement of the offset, peak, and morphology of the T wave
      in multilead ECGs are reviewed and compared. The T wave offset is the most
      important and also the most difficult measurement for analysis of QT interval
      dispersion. Measurement methods compared here include (1) the point at which the
      T wave intersects the isoelectric line plus a threshold; (2) the point at which
      the derivative of T wave intersects the isoelectric line plus a threshold; (3)
      the intersection of the maximum slope of the T wave and the isoelectric line; (4)
      the intersection of a line fitted by least squares to the maximum slope of the T
      wave and an isoelectric line (LSI); and (5) the point at which the T wave area
      reaches 90% of the entire T wave area (TA). The reproducibility tests show that
      the LSI method has the best reproducibility of all the algorithms examined.
      Although the T wave peak is better defined than the T wave offset, it is not
      simple to find the right peak when there are multiple T wave peaks and when the T
      wave is flat and/or noisy. Methods to find T wave patterns with multiple peaks
      and to locate the point at which the T wave is flat and noisy are therefore
      reviewed here. Finally, the principal component analysis-based T wave complexity
      measurement and its relation to other QT interval dispersion measurements are
      discussed.

PMID- 9535498
TI  - QT prolongation and dispersion in myocardial ischemia and infarction.
AB  - The ability of QT interval dispersion to predict the occurrence of ventricular
      fibrillation (VF) after acute myocardial infarction treated with thrombolytic
      therapy is controversial. Continuous 12-lead electrocardiographic (ECG)
      monitoring for 48 hours or longer provides an opportunity to detect transient
      changes of QT dispersion and correlate such changes with the clinical outcome. In
      543 consecutive patients enrolled in the TAMI-9 and GUSTO I studies, serial
      changes of the QT dispersion were analyzed in an attempt to predict the
      occurrence of VF with a system that monitored continuously the 12-lead ECG and
      stored it at least every 20 minutes. Measurements of QT dispersion were made at a
      median time of 2.37 hours after the onset of chest pain and at 24- and 48-hour
      intervals. A total of 43 patients experienced VF during the acute phase of
      myocardial infarction; of these patients, 33 (77%) had anterior infarcts.
      However, despite the higher preponderance of anterior myocardial infarcts in the
      VF group, patients with anterior infarcts did not have longer QT dispersion than
      those with other infarct locations. Similarly, no significant differences in the
      QT dispersion were observed at any time between the group with VF and that
      without. Women had increased QT dispersion in the initial and 24-hour ECG as
      compared with men (P = .005). However, this normalized at the 48-hour
      measurements. Despite this difference, there was no higher incidence of VF in
      female patients. In conclusion, the data suggest that QT dispersion alone is not
      sufficient to explain the occurrence of VF in the acute phase of myocardial
      infarction after thrombolytic therapy.

PMID- 9535499
TI  - TU wave area-derived measures of repolarization dispersion in the long QT
      syndrome.
AB  - The purpose of this study was to evaluate area-derived parameters of
      repolarization dispersion in LQTS patients and their unaffected family members
      and to use this analysis to challenge the concept of dispersion of repolarization
      in surface ECG. The area under the curve between the J point and the next P wave
      was measured automatically in 12 leads of the digital ECG in 34 LQTS patients and
      22 unaffected family members. The area-derived measures of repolarization
      included total repolarization area, T wave amplitude, time to accumulate the
      first (tA50) and the median (tA25-75) 50% of the total area, and the time to
      accumulate 97% of the total repolarization area (tA97). In comparison with
      unaffected family members, LQTS patients had significantly higher dispersion of
      tA50 (tA50-SD = 34 +/- 18 ms vs 11 +/- 6 ms, respectively, P < .001) and tA25-75
      (t[A25-75]-SD = 44 +/- 19 ms vs 24 +/- 15 ms, respectively, P < .001), whereas no
      significant difference was observed in the dispersion of total repolarization
      area, T wave amplitude, and time to accumulate total repolarization area (tA97-SD
      = 44 +/- 20 ms vs 53 +/- 19 ms, respectively, ns). It is concluded the analysis
      of area-derived parameters of repolarization showed that LQTS patients have
      increased interlead variability of the repolarization morphology (tA50-SD and
      t[A25-75]-SD), whereas they do not have increased dispersion of the total
      repolarization duration (tA97-SD). This observation indicates that an increase in
      traditional measures of dispersion (QT dispersion) may represent a heterogeneity
      of repolarization shape, whereas the true dispersion of the total duration of
      repolarization, which is related to electrocardiographic lead projection, is
      similar in patients and healthy subjects.

PMID- 9535500
TI  - The ECG bridge to the twenty-first century: progress report for 1997 and future
      directions: presidential talk at Palm Coast 1997.

PMID- 9535502
TI  - Germ cell apoptosis in rat testis after administration of 1,3-dinitrobenzene.
AB  - The present study investigated the occurrence of apoptosis in rat testis 6, 12,
      24, or 48 h after administration of 1,3-dinitrobenzene (DNB)(25 mg/kg, i.p.).
      Apoptotic cells were visualized using TUNEL in situ detection. In untreated
      control animals, occasional tubules contained a few apoptotic nuclei. After DNB
      treatment, more tubules were apoptotic and more germ cells within individual
      tubules were affected. The increase in incidence and severity of apoptosis was
      statistically significant 24 and 48 h after exposure. Spermatocytes were the
      primary cell population affected. Apoptosis was primarily present in Stages VI
      VIII and IX-XIII. DNA ladders, characteristic of apoptosis, were clearly present
      by 24 h after DNB administration, faint at 12 h, and not present in the control
      or at 6 h. Although initiating mechanisms may be very different for different
      chemicals, apoptosis is a common and late manifestation of the testicular
      response to numerous toxicants.

PMID- 9535501
TI  - Semen quality and sex hormones with reference to metal welding.
AB  - Welding may involve hazards to the male reproductive system, but previous studies
      of semen quality have produced inconsistent results. We studied the effects of
      welding on markers of semen quality in a Danish nationwide sample of 430 first
      time pregnancy planners without earlier reproductive experience. Couples were
      recruited among members of the union of metal workers and three other trade
      unions and were followed from termination of birth control until pregnancy for a
      maximum of six menstrual cycles. The males provided semen samples in each cycle.
      Median sperm density for welders was 56 x 10(6)/mL (52.5 x 10(6)/mL and 50.0 x
      10(6)/mL in two reference groups). No statistically significant differences
      attributable to welding were found in proportions of morphologically normal
      sperm, sperm motility assessed by computer-aided sperm analysis, or sex hormones
      (testosterone, follicle-stimulating hormone, and luteinizing hormone). These
      negative findings may not apply to populations with high-level exposure to
      welding fume or to welders exposed to other putative hazards, e.g., heat.

PMID- 9535503
TI  - Comparison of motility and membrane integrity to assess rat sperm viability.
AB  - Rat sperm motility and membrane integrity were compared as endpoints for
      viability. Sperm motility was measured by computer-assisted semen analysis
      (CASA), whereas membrane integrity was assessed by flow cytometric analysis of
      sperm stained with two nucleic acid stains, SYBR-14 and propidium iodide. The two
      techniques were compared in experiments that examined sperm viability over time
      and by analysis of known mixtures of control and freeze/thaw-killed sperm.
      Results from the two approaches were quantitatively very similar. Sperm from rats
      treated with dibromoacetic acid (600 or 1200 mg/kg) or alpha-chlorhyrin (100
      mg/kg) were also analyzed. Neither technique detected a treatment-related effect
      with dibromoacetic acid. CASA identified a significant decrease in sperm motility
      in alpha-chlorhyrin-treated rats, whereas flow cytometric analysis did not find a
      measureable change in sperm membrane integrity. Because decreases in sperm
      motility would be expected to directly affect fertility, CASA may be a more
      robust endpoint for risk assessment in reproductive toxicology studies than flow
      cytometric analysis of membrane integrity.

PMID- 9535504
TI  - Analysis of colchicine-induced chromosomal aberrations in embryos obtained from
      XO mice.
AB  - A high incidence of chromosomal anomalies has been observed in the offspring of
      our XO mouse colony. However, the reason(s) are unknown. We hypothesized that XO
      dams might be more susceptible to certain chromosomal mutagens. Therefore, we
      assessed whether the oocytes of XO mice are more susceptible to colchicine.
      Pregnant XO and XX mice were intraperitoneally (i.p.) injected with colchicine,
      0.2 mg/kg, 6 h after mating (between resumption of meiosis II and extrusion of
      the second polar body). Contrary to our expectation, the incidence of chromosomal
      anomalies induced by colchicine exposure did not differ between XX and XO dams.
      These findings suggest that the chromosomal stability of the oocytes from XO mice
      may not be affected by colchicine exposure at the stage of extrusion of the
      second polar body. The effects of chromosomal imbalance inherent in XO mice on
      chemical susceptibilities should be further investigated.

PMID- 9535506
TI  - Reproductive effects of butyl benzyl phthalate in pregnant and pseudopregnant
      rats.
AB  - In our previous studies, butyl benzyl phthalate (BBP) was found to be
      embryolethal and teratogenic in rats. In this study, the reproductive effects of
      BBP were investigated in pregnant and pseudopregnant rats. Rats were given BBP by
      gastric intubation at 0, 250, 500, 750, or 1000 mg/kg on Days 0 to 8 of pregnancy
      and the pregnancy outcome was determined on Day 20 of pregnancy. The same doses
      of BBP were given to pseudopregnant rats, with an induced decidual cell response
      on Days 0 to 8 of pseudopregnancy, and the uterine weight on Day 9 served as an
      index of the uterine decidualization. BBP caused significant increases in the
      incidences of preimplantation loss in females successfully mated at 1000 mg/kg
      and of postimplantation loss in females having implantations at 750 mg/kg and
      above. Uterine decidual growth in pseudopregnant rats was significantly decreased
      at 750 mg/kg and above. These findings suggest that early embryonic loss due to
      BBP may be mediated, at least in part, via the suppression of uterine
      decidualization, an impairment of uterine function.

PMID- 9535505
TI  - Toluene abuse embryopathy: longitudinal neurodevelopmental effects of prenatal
      exposure to toluene in rats.
AB  - To determine the longitudinal effects of prenatal exposure to toluene in rats,
      dams received daily gavage doses of toluene diluted in corn oil on Days 6 through
      19 of gestation, whereas control dams received corn oil. Litters were evaluated
      either on Gestational Day 19, Postnatal Day 10, or Postnatal Day 21; morphometric
      analysis of brain and measurements of brain DNA, cholesterol, and protein were
      made. Prenatal toluene exposure produced growth retarded fetuses with smaller
      brain and caudate-putamen volumes, fewer forebrain cell nuclei (DNA), and a
      reduction in both hindbrain cell size (protein/DNA) and myelination per cell
      (cholesterol/DNA). Postnatal catch-up growth occurred in the prenatally toluene
      exposed pups, and by Postnatal Day 21 these differences had resolved. However, on
      Postnatal Day 21, a significant reduction in forebrain myelination/cell was
      present in the prenatally toluene-exposed pups. Therefore, whereas the effects of
      toluene administered prior to the time of the brain growth spurt were, for the
      most part, reversible, these exposures resulted in reduced forebrain myelination
      that may be permanent.

PMID- 9535507
TI  - Effects of amphetamine on rat embryos developing in vitro.
AB  - Wistar rat embryos were explanted on Day 10.5 of gestation and exposed in vitro
      to amphetamine (AMP) at concentrations of 0.1, 0.4, 0.8, 1.2, or 1.6 mM for 24 h,
      and the direct dysmorphogenic effects of the drug on the embryos were examined by
      comparisons with a control group. The viability of the cultured embryos was not
      affected by the AMP treatment. The yolk sac diameter was reduced at AMP
      concentrations of 1.2 and 1.6 mM. The crown-rump length, the somite number, and
      the protein content of the embryos were decreased significantly at these two
      doses, as was the developmental score. The frequency of malformed embryos was
      increased significantly at the two highest concentrations. The malformations
      induced in treated embryos included microcephaly, neural tube defects, incomplete
      rotation of the body axis, and tortuous spinal cord. Abnormal histologic changes,
      such as derangement and necrosis of the neuroepithelial tissue, were observed in
      the embryos exposed to the two highest concentrations of the drug. The observed
      embryotoxic effects appeared to depend on the AMP concentration. Our results
      demonstrated the direct embryotoxic effects of AMP on rats. The direct
      dysmorphogenic effect of AMP might be weaker than that of methamphetamine.

PMID- 9535508
TI  - Retinoic acid-induced caudal regression syndrome in the mouse fetus.
AB  - Caudal regression syndrome (CRS) comprises developmental anomalies of the caudal
      vertebrae, neural tube, urogenital and digestive organs, and hind limbs, the
      precursors of all of which are derived from the caudal eminence. Although the
      syndrome is well recognized, the etiology and pathogenetic mechanisms are poorly
      understood. Genetic and experimental models may provide some important clues to
      the early events that precede the dysmorphogenesis in CRS. The objectives of this
      study were to determine the susceptible stages for induction of CRS and to
      ascertain the early events that precede the development of this syndrome in a
      mouse model. Single oral doses of 100, 150, or 200 mg/kg retinoic acid (RA) were
      administered to TO mice on one of Gestation Days (GD) 8 to 12, and fetuses were
      observed on GD 18. All doses administered on GD 8 or 9 resulted in CRS in a large
      number of survivors. Agenesis of the tail, caudal vertebral defects, spina bifida
      occulta/aperta, imperforate anus, rectovesicle or rectourethral fistula, renal
      malformations, cryptorchidism, gastroschisis, and limb malformations, including
      the classical mermaid syndrome (sirenomelia), were characteristic features of
      this animal model. Several craniofacial malformations accompanied CRS in the GD 8
      treatment group. Chronologic examination of treated embryos at early stages
      revealed pronounced cell death in the caudal median axis, hindgut, and neural
      tube and consequently, failure of development of the tail bud in the high-dose
      groups. In the 100 mg/kg RA group, patches of hemorrhage occurred initially that
      subsequently coalesced into large hematomas and the tail progressively regressed.
      Histologic examination revealed the onset and progression of hemorrhage, edema,
      and cell death in these embryos. Transillumination and histologic preparations
      also revealed dilation of the caudal neural tube in the prospective CRS embryos.
      Thus, a combination of cell death, vascular disruption, and tissue deficiency
      appears to be the highlight of caudal regression in this model. Symmelia appeared
      to be due to failure of fission or due to the merger of limb fields rather than a
      result of fusion of two limb buds. The data are also indicative of caudal
      agenesis in the high-dose RA groups and caudal regression due to a combination of
      vascular disruption, edema, and cell death in the lower dose groups of TO mouse
      embryos.

PMID- 9535509
TI  - Peri-implantation mouse embryos: an in vitro assay for assessing serum-associated
      embryotoxicity in women with reproductive disorders.

PMID- 9535510
TI  - Embryotoxicity of carbamazepine in rat postimplantation embryo culture after in
      vitro exposure via three different routes.
AB  - Postimplantation rat embryo culture is used widely for studies of embryotoxic
      effects on the isolated embryo after in vitro exposure to xenobiotic compounds.
      In this study, the relevance of three routes of exposure of the embryo in vitro
      was evaluated using the embryotoxic anticonvulsant carbamazepine. Embryotoxic
      effects were assessed, and analyses in conceptus tissues were done to reveal
      uptake and metabolism of the compound. Exposure via the culture medium resulted
      in neural tube defects and general retardation of growth and development. After
      injections into the amniotic or exocoelomic space, local membrane adhesions were
      found. Intra-amniotic exposure caused adhesions of the amniotic membrane with the
      embryonic neural plate, resulting in trapping of the membrane in the closing
      neural tube, as well as in open neural tube defects occurring in various areas of
      the neural tube. Only after exposure via the culture medium were amounts of
      carbamazepine detectable in the embryonic tissue, correlating with the systemic
      effects found. It is concluded that uptake from the culture medium via the yolk
      sac circulation is the relevant exposure route to be used for embryotoxicity
      effect assessment.

PMID- 9535512
TI  - Specification of left-right asymmetry in mammals: embryo culture studies of stage
      of determination and relationships with morphogenesis and growth.
AB  - The internal mammalian body plan is laterally asymmetric with a consistent
      handedness such that some organs are placed on one side (stomach on the left, for
      example) and paired organs are not symmetric (for example, there are more lung
      lobes on the right). Some chemical teratogens can affect the development of
      asymmetry, and some can cause asymmetric defects in overtly symmetric structures,
      but the mechanisms are unknown. We have used chemical treatment of rat embryos in
      culture to examine the stage at which the left-right axis is determined and show
      that all effective treatments can affect left-right axis development up to the
      early headfold stage, but not from late headfold onwards. This suggests that the
      left-right axis is determined by the late headfold stage, even though the embryo
      is overtly symmetric at this stage. It appears to be much easier to induce an
      abnormal left-right axis from late allantoic bud and early headfold stages than
      the early allantoic bud stage, but we have not established the earliest stage at
      which a response can be induced. Complete situs inversus was the most common
      chemically induced abnormality, although heart looping and body turning could be
      inverted separately, suggesting that the two phenomena are linked but not wholly
      interdependent. The treatments appeared to cause a loss of handedness, rather
      than inducing inversion, since the incidence of an abnormal left-right axis never
      exceeded 50%. All treatments except methoxamine, an alpha1 adrenergic agonist,
      induced an abnormal left-right axis in association with other morphologic defects
      and growth retardation. However, there was no relationship between the severity
      or incidence of dysmorphology, nor growth retardation, and left-right
      abnormality, suggesting that although the process that specifies lateral
      asymmetry is labile, it is independent of general growth and morphogenesis.

PMID- 9535511
TI  - Structural and gene expression abnormalities induced by retinoic acid in the
      forebrain.

PMID- 9535513
TI  - The effect of sera from women with systemic lupus erythematosus and/or
      antiphospholipid syndrome on rat embryos in culture.
AB  - Women with systemic lupus erythematosus (SLE) with or without antiphospholipid
      antibodies (APLA) suffer from a high rate of recurrent abortions perhaps as a
      result of specific antibodies that may damage the conceptus. We studied the
      effects of sera from women with SLE--with or without--APLA and recurrent
      abortions on 10.5-d-old rat embryos in culture. This was compared to the results
      of culture on sera from control women and on rat sera. In addition, we studied
      sera from women with SLE with or without APLA after treatment with low doses of
      aspirin and glucocorticosteroids. Seventy-three percent of embryos cultured in
      sera from women with SLE with or without APLA were malformed in comparison to
      only 10.2% in embryos cultured on control sera and 5.4% in embryos cultured on
      rat sera. The rate of anomalies was reduced to 37.5% in embryos cultured on sera
      from women with SLE with or without APLA after treatment, as in 6 of 13 sera, the
      treatment reduced or prevented the occurrence of embryonic anomalies. When sera
      were divided in to low- and high-risk sera, the effect of treatment was even more
      significant, as the average percentage of embryonic anomalies per serum was
      reduced from 81.7 to 44.7%. Specific ultrastructural changes were found in the
      yolk sacs of the embryos cultured on the sera from women with SLE with or without
      APLA by transmission electron microscopy and by scanning electron microscopy. It
      seems that the rat embryo culture system may be an important clinical diagnostic
      tool to identify women with recurrent abortions in whom the etiology may be
      immunologic rejection of the embryo and to assess the efficacy of various
      treatment modalities.

PMID- 9535514
TI  - Nutritional role of the visceral yolk sac in organogenesis-stage rat embryos.

PMID- 9535515
TI  - Quantitative studies on the mechanisms of amino acid supply to rat embryos during
      organogenesis.

PMID- 9535516
TI  - The role of exogenous growth-promoting factors and their receptors in
      embryogenesis.
AB  - During organogenesis, the cells of the embryo may require growth factors that
      promote a cascade of intracellular events. An absolute requirement for exogenous
      insulin by presomite 9.5-d rat embryos grown in culture has been demonstrated.
      The uptake and processing of insulin and insulin-like growth factor-I showed
      different uptake and localization patterns. When epidermal growth factor (EGF) or
      "long EGF" is added to media depleted of low molecular weight material, a dose
      dependent improvement in growth is observed. Furthermore, the specific EGF
      receptor signal transduction inhibitor Tyrphostin 47 can inhibit embryonic growth
      when it is administered in culture. When Tyrphostin 47 was microinjected into
      embryos on Day 11 and their growth and differentiation evaluated on Day 12 of
      gestation, a dose-dependent decrease in developmental score was observed. Thus,
      exogenous growth factors may be essential to normal rat development and these may
      be synthesized locally in the decidua or placental tissues. Perturbations to
      ligand-receptor interactions may be a mechanism for dysmorphogenesis.

PMID- 9535517
TI  - An elbow extension neuroprosthesis for individuals with tetraplegia.
AB  - Functional electrical stimulation (FES) of the triceps to restore control of
      elbow extension was integrated into a portable hand grasp neuroprosthesis for use
      by people with cervical level spinal cord injury. An accelerometer mounted on the
      upper arm activated triceps stimulation when the arm was raised above a
      predetermined threshold angle. Elbow posture was controlled by the subjects
      voluntarily flexing to counteract the stimulated elbow extension. The elbow
      moments created by the stimulated triceps were at least 4 N.m, which was
      sufficient to extend the arm against gravity. Electrical stimulation of the
      triceps increased the range of locations and orientations in the workspace over
      which subjects could grasp and move objects. In addition, object acquisition
      speed was increased. Thus elbow extension enhances a person's ability to grasp
      and manipulate objects in an unstructured environment.

PMID- 9535518
TI  - EEG-based communication and control: short-term role of feedback.
AB  - When people learn to control the amplitudes of certain electroencephalogram (EEG)
      components (e.g., the 8-12 Hz mu-rhythm over sensorimotor cortex) and use them to
      move a cursor to a target on a video screen, feedback about performance is
      normally provided by cursor movement and by trial outcome (i.e., success or
      failure). We assessed the short-term effects of this feedback on EEG control.
      After subjects received initial training with feedback present, feedback was
      removed intermittently for periods of several minutes. Subjects still displayed
      EEG control when feedback was removed. Removal of cursor movement alone appeared
      to have effects comparable to removal of both cursor movement and trial outcome.
      These results show that, in the short-term at least, mu-rhythm control is not
      dependent on the sensory input provided by cursor movement. They also suggest
      that feedback can have inhibitory as well as facilitory effects on EEG control,
      and that these effects vary across subjects. This finding has implications for
      the design of training procedures.

PMID- 9535519
TI  - A rate-controlled indentor for in vivo analysis of residual limb tissues.
AB  - A tissue tester was designed to enable rate-controlled indentation of the bulk
      soft tissues of lower extremity residual limbs. The tissue tester employs a
      digital linear actuator that implements rate-controlled indentation, and a load
      cell that measures the reaction force resulting from tissue indentation.
      Viscoelastic phenomena such as preconditioning, hysteresis and force relaxation
      can be assessed, and the effect of varying indentation rates on soft tissue
      stiffness can be investigated. The device accommodates indentor excursions up to
      30 mm, indentation at rates of 0 to 10 mm/s, reaction forces up to 44 N, and
      multiple loading/unloading cycles. The tissue tester is controlled via a notebook
      personal computer with a PCMCIA data acquisition card. The tissue testing trials
      are automated and the entire test system is portable and amenable for use in a
      clinical or research environment. System output consists of force-displacement
      curves from cyclic loading, and force-time curves following ramped-step
      indentation. The mean indentor positioning error was 0.071 (+/-0.75)% of the
      desired displacement. This error varied as a function of indentation and was
      approximately independent of the indentation rate. Indentation rates were
      accurate to within 0.94(+/-0.68)% of the desired value and also varied with
      indentation. Indentation of a viscoelastic foam yielded force-displacement curves
      that were consistent with that obtained from an Instron universal testing
      machine.

PMID- 9535520
TI  - Effects of alignment changes on stance phase pressures and shear stresses on
      transtibial amputees: measurements from 13 transducer sites.
AB  - Interface pressures and shear stresses were measured at 13 sites on two
      unilateral below-knee amputee subjects ambulating with lower-limb patellar-tendon
      bearing prostheses. Interface stresses at the time of the first peak in the shank
      axial force-time curve were investigated at different socket-shank alignment
      settings. Stress magnitudes ranged from 1.2 to 214.7 kPa for pressure and 0.4 to
      79.6 kPa for resultant shear stress, and changes in stress due to misalignment
      ranged from 1.3 to 80.7 kPa for pressure and from 0.2 to 38.0 kPa for resultant
      shear stress. For both subjects interface stress changes were much greater in the
      anterior socket region than in the lateral or posterior regions. Thus, alignment
      changes had a localized effect on interface stresses. Plots of alignment versus
      pressure or resultant shear stress were nonlinear for both subjects, in a number
      of cases maximizing or minimizing at the nominal alignment, indicating complex
      interface stress-alignment relationships. Variation (standard deviation/mean) was
      not significantly different for nominal versus misaligned steps, indicating that
      the subjects adapted well to the alignment changes. Session to session
      differences in interface stresses were typically larger than interface stress
      differences induced by alignment modifications. Thus, while these subjects
      compensated well for alignment changes to maintain consistent interface stresses
      within a session, they did not do so for different sessions conducted weeks
      apart.

PMID- 9535521
TI  - Control of stance during lateral and anterior/posterior surface translations.
AB  - The purpose of this study was to compare and contrast postural responses to
      lateral and A/P surface translations by quantifying joint positions, bilateral
      three-dimensional (3-D) ground reaction forces, and lower limb and trunk muscle
      electromyographic (EMG) activity. Subjects stood on a movable platform which was
      randomly translated in four different directions. The kinematic patterns in
      response to lateral and anterior/posterior (A/P) surface translations were
      similar in that there was a sequential displacement and reversal of the
      shank/thigh and then trunk segments. While the body center of mass (CoM) was
      displaced equally in response to lateral and A/P translations, equilibrium was
      maintained by redistributing the vertical forces and changing the shear forces
      exerted against the support surface. These force responses were bilaterally
      symmetrical for A/P translations but not for lateral translations. With respect
      to EMG activity, the first muscle activated was the proximal tensor fascia latae
      for lateral translations whereas the distal muscles were recruited first for A/P
      translations. Results from this study suggest that control of postural
      equilibrium may be similar for A/P and lateral translations, although specific
      differences in patterns may reflect various biomechanical constraints of the
      trunk and the lower extremities associated with the two planes of movement.

PMID- 9535522
TI  - Stepping over obstacles during locomotion: insights from multiobjective
      optimization on set of input parameters.
AB  - In this study we investigate possible objectives that the central nervous system
      (CNS) may consider in planning a strategy for stepping over an obstacle. A link
      segment simulation model has been developed based on Lagrangian dynamics, with
      which muscle force inputs can be optimized to best satisfy the postulated
      objectives for landing stability, obstacle clearance, and efficiency of the
      movement. A direct optimization approach with multiobjective criteria based on
      the kinematic and kinetic characteristics of the swing phase of locomotion is
      used in the simulation. The role of initial conditions at toe-off and biarticular
      muscle forces during the swing phase was also investigated. The optimization was
      performed for both leading limb and the trailing limb during the swing phase. The
      simulation results demonstrate that the use of biarticular muscles is sufficient
      to clear a range of obstacles with the trailing limb (obstacle encountered during
      early swing). Stride length or landing stability objectives need not be specified
      suggesting a simpler control of trailing limb trajectory by the CNS (one of
      stride length or landing stability objectives were not necessary). In contrast
      while the use of biarticular muscles can be sufficient to clear obstacles with
      the leading limb (obstacle encountered during mid to late swing), a stable
      landing and smooth toe and knee trajectories are compromised without suitable
      initial conditions at toe-off. The results suggest that the set of postulated
      objectives for the lead limb is adequate, although not complete.

PMID- 9535523
TI  - A programmable sound processor for advanced hearing aid research.
AB  - A portable sound processor has been developed to facilitate research on advanced
      hearing aids. Because it is based on a digital signal processing integrated
      circuit (Motorola DSP56001), it can readily be programmed to execute novel
      algorithms. Furthermore, the parameters of these algorithms can be adjusted
      quickly and easily to suit the specific hearing characteristics of users. In the
      processor, microphone signals are digitized to a precision of 12 bits at a
      sampling rate of approximately 12 kHz for input to the DSP device. Subsequently,
      processed samples are delivered to the earphone by a novel, fully-digital class-D
      driver. This driver provides the advantages of a conventional class-D amplifier
      (high maximum output, low power consumption, low distortion) without some of the
      disadvantages (such as the need for precise analog circuitry). In addition, a
      cochlear implant driver is provided so that the processor is suitable for hearing
      impaired people who use an implant and an acoustic hearing aid together. To
      reduce the computational demands on the DSP device, and therefore the power
      consumption, a running spectral analysis of incoming signals is provided by a
      custom-designed switched-capacitor integrated circuit incorporating 20 bandpass
      filters. The complete processor is pocket-sized and powered by batteries. An
      example is described of its use in providing frequency-shaped amplification for
      aid users with severe hearing impairment. Speech perception tests confirmed that
      the processor performed significantly better than the subjects' own hearing aids,
      probably because the digital filter provided a frequency response generally
      closer to the optimum for each user than the simpler analog aids.

PMID- 9535524
TI  - A PC-based Braille library system for the sightless.
AB  - This paper presents a novel multiclient braille reading system developed around a
      single low cost personal computer. The system primarily addresses the needs of
      the Braille libraries, where different texts are needed to be read by different
      users simultaneously. Moreover, the system can simultaneously cater to different
      texts written in different languages. This feature makes it specially suitable
      for use by multilingual nationalities. The major advantage of this system is its
      low cost, compared to the other systems available and is specially attractive for
      the developing or underdeveloped countries. The paper describes the system, first
      from the user point of view and then presents the hardware and software design
      details. The system performance has been evaluated by the sightless users and has
      shown encouraging results.

PMID- 9535525
TI  - Design of a miniaturized ultrasonic bladder volume monitor and subsequent
      preliminary evaluation on 41 enuretic patients.
AB  - Nocturnal incontinence (enuresis) affects 20% of children over four years old,
      and this figure typically decreases by 15% each year. At the age of 18, 1% of
      those people remain enuretic. Nocturnal enuresis can be treated by means of a
      conditioning device that awakens the patient once the urine level has reached a
      preestablished threshold of the capacity of his or her bladder. We have designed
      and implemented a portable miniaturized ultrasonic monitor, which permits
      estimation of the urine volume with an accuracy of 75%. Prototypes have been
      completed and validated on 41 patients (children) at Ste. Justine Hospital
      (Montreal). On the first group of 33 patients, we used a hand-held transducer to
      determine the volume detection range, which is accurate for volumes between 40
      and 400 mL. With the second group of 8 patients, the device was mounted on an
      elastic belt around the abdomen. Measurements were taken in order to validate the
      accuracy of urine threshold detection and the activation of the corresponding
      alarm.

PMID- 9535527
TI  - An electromechanical testing device for assessment of hand motor function.
AB  - Instrumentation was designed and constructed to assess the strength and function
      of the intrinsic muscles of the index and long fingers of the hand. The device
      consisted of two beams instrumented with strain gages, signal conditioners, and a
      microprocessor-based embedded controller. A study conducted on four weak spinal
      cord injury (SCI), three nonweak SCI, and 21 control subjects demonstrated a
      trend of reduced maximum pinching force between the index and long fingers in
      weak SCI subjects compared with the other two groups. Weak SCI subjects also
      demonstrated a significantly slower rapid alternating movement speed of the index
      finger compared with the other two groups. The instrument has potential use as a
      clinical tool for quantitative evaluation of the progression of hand motor
      dysfunction.

PMID- 9535526
TI  - Robot-aided neurorehabilitation.
AB  - Our goal is to apply robotics and automation technology to assist, enhance,
      quantify, and document neurorehabilitation. This paper reviews a clinical trial
      involving 20 stroke patients with a prototype robot-aided rehabilitation facility
      developed at the Massachusetts Institute of Technology, Cambridge, (MIT) and
      tested at Burke Rehabilitation Hospital, White Plains, NY. It also presents our
      approach to analyze kinematic data collected in the robot-aided assessment
      procedure. In particular, we present evidence 1) that robot-aided therapy does
      not have adverse effects, 2) that patients tolerate the procedure, and 3) that
      peripheral manipulation of the impaired limb may influence brain recovery. These
      results are based on standard clinical assessment procedures. We also present one
      approach using kinematic data in a robot-aided assessment procedure.

PMID- 9535528
TI  - Multidimensional electrocutaneous stimulation.
AB  - Probing the subjective response to a five-parameter electrocutaneous stimulus has
      revealed a noisy perceptual space. A method for reducing the noise is
      hypothesized and experimentally tested by comparing the intensity discrimination
      thresholds along and off the energy gradient. Preliminary results show a
      reduction of the threshold of up to 60% when stimulating along the gradient. The
      method is exploited to implement an optimal intensity control in an
      electrotactile vision-substitution device.

PMID- 9535529
TI  - Issues in impedance selection and input devices for multijoint powered orthotics.
AB  - We investigated the applicability of impedance controllers to robotic orthoses
      for arm movements. We had tetraplegics turn a crank using their paralyzed arm
      propelled by a planar robot manipulandum. The robot was under impedance control,
      and chin motion served as command source. Stiffness varied between 50, 100, or
      200 N/m and damping varied between 5 or 15 N/m/s. Results indicated that a low
      stiffness and high viscosity provided better directional control of the
      tangential force exerted on the crank.

PMID- 9535530
TI  - Developmental regulation of the inhibitory effect of dopamine on prolactin
      release in the preterm neonate.
AB  - The secretion and release of prolactin from the anterior pituitary is under the
      tonic inhibitory control of endogenous dopamine produced in the central nervous
      system. Exogenous dopamine inhibits prolactin secretion by reaching the pituitary
      via the portal circulation, and the hypolactotropic effect of dopamine infusion
      has been documented in all age groups in humans. However, the maturation of
      lactotroph sensitivity to dopaminergic inhibition has not been studied.
      Therefore, we followed the changes in serum prolactin concentrations before,
      during, and after dopamine infusion in 19 sick preterm infants with a mean
      gestational age of 30.6+/-0.6 weeks during the first 3 days of life, and examined
      the relationship of the hypolactotropic effect of dopamine to gestational age and
      birth weight in this patient population. As expected, dopamine therapy resulted
      in a decrease in mean serum prolactin from 89.4+/-9.5 to 58.6+/-9.1 microg/l (p <
      0.05) with a return of the serum prolactin concentration to the pretreatment
      level 2-6 h after discontinuation of drug administration (98.3+/-11.7 microg/l, p
      < 0.05). However, simple regression analysis of the individual data revealed that
      the magnitude of the dopamine-induced decrease in serum prolactin was
      significantly influenced by gestational age (p = 0.006) and birthweight (p =
      0.037). Thus, our findings provide evidence for the maturation of pituitary
      lactotroph sensitivity to dopaminergic inhibition in the preterm human neonate.

PMID- 9535531
TI  - Movement quality in preterm infants prior to term.
AB  - Quality of spontaneous movement behavior (fluency, spatio-temporal variation and
      sequencing) was studied from birth to term in high-risk preterm (n = 18), low
      risk preterm (n = 18) and term (n = 20) infants. Cranial ultrasonography was
      performed during the first week of life and the child's general health was
      considered. The results were as follows: (1) In their first week of life, preterm
      infants displayed lower scores on all quality parameters when compared to term
      infants (p < 0.001). (2) Quality of spatiotemporal variation and sequencing
      decreased up to term (p < 0.01). These findings could be attributed to
      maturational differences, too early exposure to an extrauterine environment, and
      cerebral lesions.

PMID- 9535532
TI  - Unconjugated and conjugated bilirubin pigments during perinatal development. V.
      Effect of phototherapy on serum conjugated bilirubin in hyperbilirubinemic
      neonates.
AB  - OBJECTIVE: To determine the effect of phototherapy on serum conjugated bilirubin
      fractions, an index of bilirubin conjugation, in hyperbilirubinemic neonates.
      METHOD: Serum was sampled from 21 jaundiced (serum diazo total bilirubin > or =
      274 micromol/l), term, otherwise healthy neonates prior to starting phototherapy,
      and 24 h after the commencement of treatment. Alkaline methanolysis followed by
      reverse-phase, high-performance liquid chromatography, specific for determination
      of unconjugated bilirubin and the monoconjugated and diconjugated fractions of
      total conjugated bilirubin in serum, was used for the analysis. Prephototherapy
      values were compared to those at 24 h. RESULTS: Serum total bilirubin and total
      conjugated bilirubin values decreased during the study period, from 220 (211-239)
      to 177 (157-213) micromol/l (median (25-75% range)) p = 0.001, for the former,
      and from 1.4 (0.87-1.57) to 0.93 (0.69-1.84) micromol/l, p = 0.005, for the
      latter. These parameters decreased by a similar percentage (-16.6+/-14.8% and -
      14.0+/-23.4%, respectively; p > 0.05). Both monoconjugated and diconjugated
      bilirubin, calculated as a percentage of total conjugated bilirubin, remained
      constant over the study period (88.2 (72.2-96.4)% before phototherapy and 92.5
      (87.3-96.8)% after 24 h, p > 0.05, for monoconjugated bilirubin, and 11.8 (3.6
      27.8)% and 7.5 (3.2-12.7)%, respectively, p > 0.05, for diconjugated bilirubin).
      CONCLUSIONS: Serum total conjugated bilirubin values decreased in parallel to
      serum total bilirubin levels during phototherapy, maintaining a constant
      relationship between these two parameters. The ratios of monoconjugated and
      diconjugated bilirubin to total conjugated bilirubin remained constant. These
      findings imply that phototherapy does not alter bilirubin conjugation in
      hyperbilirubinemic neonates.

PMID- 9535533
TI  - Cardiac troponin T in newborn infants with transient myocardial ischemia.
AB  - Cardiac troponin T (TnT) is a regulatory contractile protein whose detection in
      the circulation has been shown to be a specific and sensitive marker for ischemic
      myocardial cell injury both in adult and pediatric populations. We measured serum
      cardiac TnT in 15 consecutive full-term neonates presenting with bradycardia and
      electrocardiographic features of transient myocardial ischemia. Their median TnT
      concentrations (0.5 microg/l, range 0.01-0.37) were statistically comparable to
      our laboratory reference values for healthy term newborns (median 0.17 microg/l,
      range 0.01-0.42) (p = NS), but significantly higher with respect to our reference
      limits for healthy adults (median 0.01 micog/l, range 0.01-0.1) (p < 0.05). Our
      data demonstrate high TnT levels in neonates during the first days of life with
      respect to adults and similar TnT concentrations in term infants with and without
      TMI.

PMID- 9535534
TI  - Platelet activation during the early neonatal period.
AB  - The first week of life is a time when hereditary or more frequently acquired
      factors lead to some important differences in the hemostatic mechanism of the
      newborn. It has been well known that ill neonates are prone to both hemorrhage
      and thrombosis. The aim of this study was to answer the question of whether there
      is a difference in platelet activation in healthy neonates during the first days
      of life that may contribute to both hemorrhage and thrombosis in the presence of
      additional pathologic insults. Platelet activation was determined with flow
      cytometry using monoclonal antibodies in 63 healthy children (29 neonates, 17
      infants, and 17 older children). There was no significant difference in platelet
      activation among these three age groups (p > 0.05). In addition, platelet
      activation did not show any significant relationship to age, sex, mode of
      delivery, or blood bilirubin concentration (p > 0.05). It has been previously
      reported that platelet activation occurs at the time of birth. We could not find
      any evidence that healthy newborns during the first 3 days of life exhibit
      increased platelet activation. Further studies on platelet activation in ill
      neonates will help to clarify whether platelet activation plays a role in the
      pathogenesis of thrombotic and/or hemorrhagic disorders.

PMID- 9535536
TI  - A single dose of antenatal betamethasone enhances isoprenaline and prostaglandin
      E2-induced relaxation of preterm ovine pulmonary arteries.
AB  - Beta-adrenergic agonists and prostaglandin E2 (PGE2) play an important role in
      perinatal pulmonary circulation. We have determined the effect of antenatal
      glucocorticoid treatment on isoprenaline- and PGE2-mediated relaxation of
      pulmonary arteries of newborn preterm lambs. Ovine fetuses (121 days of
      gestation; term = 150 days) received a single intramuscular dose of betamethasone
      (0.5 mg/kg) or saline. Fifteen hours after the injection, the lambs were
      delivered, ventilated for 3 h, and sacrificed. The fourth-generation pulmonary
      arteries were dissected and cut into rings for study. In endothelin-1
      preconstricted vessels, isoprenaline, PGE2, and forskolin (an activator of
      adenylyl cyclase) induced greater relaxations of pulmonary arteries of
      betamethasone-treated lambs than those of controls. 8-Bromo-cyclic adenosine
      monophosphate, a cell membrane permeable analogue of cyclic adenosine
      monophosphate, caused similar relaxation of all vessels. When stimulated with
      isoprenaline and PGE2, the adenylyl cyclase activity of crude membrane
      preparations of pulmonary arteries treated with betamethasone was greater than
      that of controls. These results show that single-dose antenatal betamethasone
      treatment enhances relaxation of pulmonary arteries of preterm lambs induced by
      isoprenaline and PGE2 and that an enhanced adenylyl cyclase activity contributes
      to the effect of betamethasone on pulmonary arteries of preterm lambs.

PMID- 9535537
TI  - Developmental control of argininosuccinate lyase gene by methylation.
AB  - The gene of argininosuccinate lyase (ASL) is expressed in a developmental
      specific manner in the liver and is regulated by hormones, namely
      glucocorticoids, glucagon and insulin. To assess the role of DNA methylation in
      the developmental pattern of ASL gene expression, we analyzed the restriction
      profile obtained by cleavage of genomic DNA with MspI and HpaII in fetal and
      adult rat liver, two developmental stages with different levels of expression of
      the ASL gene. Southern analysis showed that the 5' region of this gene appeared
      more methylated in the fetal liver which expressed ASL at a low level than in the
      adult liver where the ASL gene is highly expressed. Moreover, treatment of
      fetuses of various gestational stages with the hypomethylating agent 5
      azacytidine for 18 h caused an increase of the hepatic ASL activity and mRNA
      level. The stimulating effect of this drug could be also observed in vitro in
      cultured fetal hepatocytes. These results suggest a developmental control of the
      ASL gene by the DNA methylation status.

PMID- 9535535
TI  - Inhaled nitric oxide neither alters oxidative stress parameters nor induces lung
      inflammation in premature lambs with moderate hyaline membrane disease.
AB  - The purpose of this investigation was to examine whether inhaled nitric oxide
      (NO) may alter oxidative stress parameters and induce lung inflammation in
      moderate hyaline membrane disease (HMD). Eighteen moderately premature lambs (130
      days gestation, term = 147 days) were randomly assigned to treatment with 20 ppm
      inhaled NO (n = 8) from the onset of ventilation or used as control (n = 10).
      Except inhaled NO, treatments were intentionally similar to those applied in
      clinical situations. The main studied parameters were oxidative stress index
      measurements on lung parenchyma and in circulating blood, lung parenchyma
      microscopic examination and bronchoalveolar lavage cell count. We found that 20
      ppm of inhaled NO for 5 h did not change significantly either malondialdehyde and
      total antioxidant status levels in circulating blood, or malondialdehyde, reduced
      glutathione, glutathione peroxidase and glutathione reductase in lung parenchyma.
      Amino-imino-propene bond generation, which are lipoperoxidation markers, was
      similar in both groups. Furthermore, no significant changes in the number of
      inflammatory cells in lung lavage products and in lung parenchyma microscopic
      examination could be found. Therefore, these data do not support the hypothesis
      that short-term NO inhalation increases oxidative stress and lung inflammation in
      an experimental model of moderate HMD.

PMID- 9535538
TI  - Effects of a continuous epinephrine infusion on regional blood flow in awake
      newborn piglets.
AB  - OBJECTIVE: To determine the effects of a continuous epinephrine infusion on renal
      and mesenteric blood flow in both healthy newborn piglets and animals subjected
      to hemorrhagic shock. METHODS: Superior mesenteric artery (SMA) and left renal
      artery ultrasonic flow probes were implanted into 16 1- to 3-day-old piglets. Two
      days later, the effects of epinephrine on SMA and renal blood flow, mean arterial
      pressure (MAP) and central venous pressure were measured in conscious, non
      sedated normovolemic piglets. Epinephrine doses of 0.2, 0.4, 0.8, 1.6 and 3.2
      microg/kg.min were used in random order. Piglets were subsequently hemorrhaged
      (20 ml/kg) to mild hypotension and again received epinephrine infusion in the
      same doses. RESULTS: Doses of epinephrine less than 3.2 microg/kg.min had no
      significant effects on renal or mesenteric arterial flow. At 3.2 microg/kg.min of
      epinephrine during normovolemia, there was a significant decrease in SMA blood
      flow (34% [SD 42], p < 0.05) and increase in SMA vascular resistance (147% [SD
      114], p < 0.05). Similar results were shown during hypovolemia, SMA flow
      decreased by 32% (SD 33), and SMA vascular resistance increased by 220.3% (SD
      177). At 3.2 microg/kg.min renal artery flow decreased by 43% (SD 21) during
      normovolemia and a similar decrease occurred during hypovolemia, 37% (SD 31).
      Renal vascular resistance increased by about 200% at this dose (normovolemia 211%
      [SD 185], hypovolemia 186% [SD 150], p < 0.01). Low-to-moderate dose epinephrine
      caused no significant change in SMA or renal blood flow. During hypovolemia low
      dose epinephrine infusion was associated with a trend to increased SMA blood
      flow. CONCLUSION: Low-dose epinephrine does not cause vasoconstriction in the
      renal or mesenteric circulations during normovolemia or hypovolemia. High doses
      of epinephrine above 1.6 microg/kg.min may cause renal or mesenteric ischemia, in
      either the normovolemic or hypovolemic neonate.

PMID- 9535539
TI  - Is there a COX-fight during inflammation?

PMID- 9535540
TI  - Evidence of a key-role for histamine from mast cells in the analgesic effect of
      clomipramine in rats.
AB  - OBJECTIVE AND DESIGN: We investigated the role of neuronal and mast cell
      histamine in the analgesic effect of clomipramine. SUBJECTS: Male Sprague-Dawley
      rats (4-6 weeks old) were used (n = 228). TREATMENT: Clomipramine (10, 20 or 40
      mg/kg i.p.) was injected in rats pretreated with [a] saline i.cv. or i.p., [b]
      alpha-fluoromethylhistidine (alpha-FMH, 200 microg i.cv.), [c] compound 48/80
      (C48/80, 1 mg/kg i.p.). Other rats were pretreated with clomipramine, before
      C48/80. METHODS: Antinociceptive responses were determined before and 30, 60, 90,
      120 min after drug injection by tail-flick (TFT) and hot-plate (HPT) tests.
      Results for each treatment group are given as mean %MPE +/- SEM (Student's t
      test, ANOVA). RESULTS: Clomipramine produced no significant changes in TFT and
      HPT in saline- or alpha-FMH-pretreated rats. Following C48/80, clomipramine (10
      and 20 mg/kg) produced a dose-related significant increase in latencies, between
      30 and 120 min: 28.5 +/- 5.7 vs 8 +/- 1.6 (p < 0.05), 56 +/- 5 vs 9.2 +/- 1.9 (p
      < 0.01) in TFT; 31 +/- 4.3 vs 12 +/- 2.5 (p < 0.05), 46.2 +/- 6 vs 11.5 +/- 1.9
      (p < 0.01) in HPT. Clomipramine (40 mg/kg, after C48/80) produced marked and
      persistent increase in latencies 83.2 +/- 4.2 vs 10.5 +/- 3 (p < 0.01) in TFT and
      91.2 +/- 4.6 vs 10.5 +/- 3 (p < 0.01) in HPT, followed by symptoms of toxicity
      and death of some animals. In rats pretreated with clomipramine, C48/80 was
      unable to show antinociceptive effects on TFT and HPT. CONCLUSIONS: Results
      suggest that the antinociceptive effect of clomipramine may depend on mast cell
      histamine levels.

PMID- 9535541
TI  - Modulation of peripheral inflammation by locally administered hemorphin-7.
AB  - OBJECTIVE: Sensory nerves mediate peripheral inflammation via the release of
      sensory peptides at the site of tissue injury. Using a blister model of
      inflammation, we have previously documented that endogenous opioids modulate
      chronic but not acute inflammation. Hemorphins are nonclassical opioid peptides
      found in the region of the beta-chain of hemoglobin (Hb). The heptapeptide
      hemorphin-7 is identical with residues 35-41 of the beta-chain of the human Hb.
      The aim of this study was to examine the effect of hemorphin-7 on the
      inflammatory response in acute and chronic injury models. METHODS: We have used a
      vacuum-induced blister model in the footpad of anaesthetized rats to induce an
      inflammatory response in naive skin by (a) electrical stimulation (ES) of the
      distal end of the cut sciatic nerve at 20 V, 5 Hz, 2 ms for 1 min or (b)
      superfusion of sensory peptides; substance P (SP) or calcitonin gene related
      peptide (CGRP) over the blister base. In addition, we examined the effect of
      hemorphin-7 on the inflammatory response to SP induced in a previously injured
      but healed skin site (recurrent injury model) and in denervated skin site due to
      chronic nerve lesion (chronic injury model). RESULTS: The results showed that
      prior and concomitant perfusion of hemorphin-7 over the blister base inhibited
      the acute inflammatory response to ES of the sciatic nerve at C-fibre strength in
      a dose-dependent manner. Significant inhibition was achieved at 20 and 200 microM
      concentration of hemorphin-7. When hemorphin-7 (20 microM) was perfused prior to
      and together with SP or CGRP (both at 1 microM), over the base of acutely induced
      blister in naive skin, it significantly reduced the inflammatory response to SP
      (both plasma extravasation and vasodilatation), but was without effect on the
      vasodilatation response to CGRP. Naloxone, the general opioid antagonist at (1
      mg/kg i.v.) reversed the inhibitory effect of hemorphin-7 on the inflammatory
      response to SP. On the other hand, hemorphin-7 had no effect on the inflammatory
      response to SP in the recurrent injury or the chronic injury models. CONCLUSIONS:
      The results of this study suggest that hemorphins might play a role in inhibiting
      the inflammatory response in acute, but not in recurrent or chronic injury
      conditions. Evidence is also provided that the modulatory inhibitory effect of
      hemorphin-7 is mediated via activation of opioid receptor(s). The significance of
      this study in conjunction with our previous work, is that it raises the
      possibility that different endogenous inhibitory mechanisms may operate under
      different injury conditions - endogenous hemorphins and opioids may modulate
      acute and chronic inflammation, respectively.

PMID- 9535542
TI  - Evaluation of the cutaneous anti-inflammatory activity of azaspiranes.
AB  - OBJECTIVE AND DESIGN: The ability of azaspiranes to modulate the acute
      inflammatory response in models of skin inflammation was examined. MATERIAL: The
      in vivo experiments involved the use of 5-6 age-matched male Balb/c inbred mice
      (22-25 g) per treatment group and a control group of 8-10 animals. In vitro
      mechanistic studies used RBL-1 and U937 cells lines and freshly isolated human
      monocytes. TREATMENT: Arachidonic acid (AA) (2 mg/20 microl in acetone) or PMA
      (phorbol myristate acetate) (4 microg/20 microl) were applied topically. SK&F
      106615 and SK&F 106610 were administered topically either dissolved in acetone or
      dimethylacetamide just after the application of the irritant. Isolated cells were
      treated with the compounds dissolved in DMSO. METHODS: The thickness and influx
      of neutrophils into the treated ears was measured as was the effects of the
      azaspiranes on 5-lipoxygenase activity, cyclooxygenase activity, prostaglandin
      and leukotriene synthesis, and the activation of the transcription factor NF
      kappaB. RESULTS: SK&F 106615 and SK&F 106610 significantly reduced inflammation
      in the AA- and PMA-induced inflammation models (p < 0.05) with ED50's of 179 and
      120 mg/ear for edema and myeloperoxidase, respectively. The compounds did not
      inhibit eicosanoid biosynthesis, have a direct effect on 5-lipoxygenase or
      cyclooxygenase enzymes, or inhibit NF-kappaB. CONCLUSIONS: The potent anti
      inflammatory and immunomodulatory activities of the azaspiranes observed in these
      and other studies appear to be mediated by a novel mechanism.

PMID- 9535543
TI  - Effects of cyclosporin A and glucocorticosteroids on antigen-induced
      hypersensitivity to histamine in a guinea pig model of allergic rhinitis.
AB  - OBJECTIVE AND DESIGN: In an attempt to study the pathogenesis of mucosal
      hypersensitivity in allergic rhinitis, we investigated the suppressive effects of
      cyclosporin A (CyA) and glucocorticosteroids on ovalbumin (OA)-induced
      hypersensitivity to topical histamine challenge. MATERIALS: Actively sensitized
      Dunkin-Hartley guinea pigs. TREATMENT: OA and alum were applied to guinea pigs
      intraperitoneally 3 times at two-week intervals. After general sensitization, OA
      inhalation was performed every day for 6 days as topical sensitization. Before
      inhalation, treatment with CyA (50 mg/kg, p.o.), glucocorticosteroids
      (beclomethasone propionate (1.0 mg/kg, i.p.), fluticasone propionate (FP, 0.5
      mg/kg, i.p.)) or vehicle were performed, and the sensitivity to histamine was
      measured before and after the inhalation. Moreover, in actively (general and
      topical) sensitized guinea pigs, FP (0.5 mg/kg, i.p.) was applied every day for 5
      days and histamine sensitivity was evaluated before and after the application.
      RESULTS: We found that histamine sensitivity was significantly increased by nasal
      antigen challenge in this guinea pig model, and that the occurrence of histamine
      hypersensitivity was inhibited by the pretreatment with CyA and
      glucocorticosteroids. Although multiple administration of FP gradually reduced
      the histamine hypersensitivity according to the period of administration, it did
      not significantly alter the histamine hypersensitivity after the occurrence of
      hypersensitivity. CONCLUSION: It is concluded that CyA and glucocorticosteroids
      suppress antigen-induced histamine hypersensitivity in a guinea pig model of
      allergic rhinitis.

PMID- 9535544
TI  - Evaluation of neutrophil functions after experimental abdominal surgical trauma.
AB  - OBJECTIVE: In order to determine the effect of surgical trauma on neutrophil
      functions, we set up an experimental abdominal surgical model using rats and
      analyzed neutrophil functions. In addition, we measured tumor necrosis factor
      alpha (TNF-alpha), cytokine-induced neutrophil chemoattractant/growth-regulated
      oncogene (CINC/GRO) and nitric oxide (NO) production. MATERIALS AND METHODS: Male
      Sprague-Dawley rats, 8 weeks old and weighing 250-270 g, underwent laparotomy (4
      rats for each experiment). After the operation, neutrophil chemotaxis was assayed
      using a modified Boyden chamber, and phagocytosis, active oxygen production and
      adhesion molecule expression were analyzed by flow cytometry. TNF-alpha and
      CINC/GRO levels were quantified by an immuno-dot-blot assay, and NO levels were
      measured by the Griess method. At the operation, NO inhibitor, N(G)-monomethyl-L
      arginine acetate (L-NMMA, 40 mg) was intraperitoneally administered, and the
      effect of L-NMMA was studied. RESULTS: After the surgical trauma (24-48 h), blood
      neutrophil counts significantly increased (p < 0.001), and neutrophil chemotaxis,
      phagocytosis and active oxygen production were markedly enhanced (p < 0.01).
      Moreover, up-regulation of Mac-1 and down-regulation of L-selectin on neutrophils
      were observed (p < 0.05). The levels of TNF-alpha, CINC/GRO and NO increased
      remarkably in both blood and ascites at 8-48 h after the surgical trauma (p <
      0.01): TNF-alpha increased from 194 +/- 9 (the mean +/- SD, n = 4) and 183 +/- 12
      pg/ml (preoperation) to 797 +/- 28 and 1045 +/- 137 pg/ml at 24 h in blood and
      ascites, respectively; CINC/GRO increased from 0.1 +/- 0 and 0.1 +/- 0 ng/ml (pre
      operation) to 66.4 +/- 4.5 and 60.3 +/- 17.9 ng/ml at 8 h in blood and ascites,
      respectively; NO increased from 2.4 +/- 1.0 and 4.2 +/- 1.1 microM (pre
      operation) to 11.9 +/- 0.7 and 36.9 +/- 2.1 microM in blood and ascites at 24 h
      and 48 h in blood and ascites, respectively. Interestingly, L-NMMA treatment
      significantly reduced the increased levels of TNF-alpha and CINC/GRO and altered
      the enhanced neutrophil functions (p < 0.05). CONCLUSION: These observations
      indicate that abdominal surgical trauma induces the production of NO, TNF-alpha
      and CINC/GRO, and enhances neutrophil functions such as chemotaxis, phagocytosis
      and active oxygen production. Furthermore, L-NMMA likely modulates the neutrophil
      functions and the production of TNF-alpha and CINC/GRO after the surgical trauma.

PMID- 9535545
TI  - Anti-inflammatory action of pale sulfonated shale oil (ICHTHYOL pale) in UVB
      erythema test.
AB  - OBJECTIVE AND DESIGN: In a clinical research institute the anti-inflammatory
      effect of pale sulfonated shale oil versus hydrocortisone was investigated in a
      placebo-controlled clinical trial using a double-blind design and random
      assignment of the treatments to the test fields. SUBJECTS: 20 male and female
      volunteers with healthy skin in the test areas participated in this trial.
      TREATMENT: All subjects received different concentrations of pale sulfonated
      shale oil (2% and 4%), the active ingredient-free vehicle and a reference product
      containing 0.5% hydrocortisone. METHODS: Approximately 300 microl of test
      preparation were applied to the treatment fields. The medication was administered
      for 23 h. An untreated, irradiated and an untreated, non-irradiated control field
      were included as well. The test fields were compared intraindividually. Four
      different UV-doses (1; 1.25; 1.6 and 2 MED) were tested in each volunteer. The
      test fields were occluded for 6 h. After 7 h, measurement with a colorimeter was
      carried out. After measurement, the treatment was repeated. The test fields were
      occluded for a further 16 h and test preparations carefully wiped off. One hour
      later, post-irradiation color measurements were made by colorimetric detection.
      Variance analysis was used for statistical evaluation. RESULTS: 4% pale
      sulfonated shale oil and 0.5% hydrocortisone had a significantly greater efficacy
      than the vehicle (p = 0.0001). There were no differences between the efficacy of
      4% pale sulfonated shale oil and 0.5% hydrocortisone (p = 0.5169). CONCLUSIONS:
      These results demonstrate the anti-inflammatory efficacy of 4% pale sulfonated
      shale oil and help explain the clinical effects of the drug in the therapy of
      atopic eczema.

PMID- 9535546
TI  - Differential effects of inhibition of isoforms of cyclooxygenase (COX-1, COX-2)
      in chronic inflammation.
AB  - OBJECTIVE AND DESIGN: The anti-inflammatory effects of therapeutic dosing of
      drugs with greater selectivity for the inhibition of the constitutive (COX-1) or
      inducible isoform (COX-2) of cyclooxygenase were assessed in a model of chronic
      inflammation. METHODS: The murine chronic granulomatous tissue air pouch model
      involves the subcutaneous injection of air into the dorsum of mice followed 24 h
      later by the intrapouch injection of an inflammatory stimulus (0.5 ml of Freund's
      complete adjuvant containing 0.1% croton oil). Aspirin, more selective in vitro
      for the inhibition of COX-1 (10,200 (mg/kg) and nimesulide, a selective in vitro
      inhibitor of COX-2 (0.5, 5 mg/kg) were dosed p.o. daily from 3 days after
      injection of the inflammatory stimulus. Granuloma dry weight, vascularity and COX
      activity (measured as PGE2) were assessed at various time points throughout the
      inflammatory lesion to resolution at day 28. A second COX-2 inhibitor, NS 398
      (0.1, 1, 10 mg/kg), was dosed p.o. daily from 3 days after the injection of the
      inflammatory stimulus and its effects on granuloma dry weight, vascularity and
      COX activity were measured at 7 days. RESULTS: Aspirin (200 mg/kg) significantly
      inhibited levels of PGE2 throughout the time course and at the lower dose (10
      mg/kg) from day 14. Nimesulide (5 mg/kg) however, significantly increased levels
      of PGE2 at days 5 and 21, but at 0.5 mg/kg was without effect. Aspirin (200
      mg/kg) significantly reduced granuloma dry weight at day 14 but had no effect on
      granuloma vascularity at day 7. In contrast, nimesulide (5 mg/kg) significantly
      increased granuloma vascularity at day 7 and granuloma dry weight at day 14. NS
      398 at all doses had no effect on granuloma dry weight, vascularity or COX
      activity 7 days after the injection of the inflammatory stimulus. CONCLUSION: In
      this model of chronic inflammation, aspirin, more selective for the inhibition of
      COX-1 is more effective than the selective COX-2 inhibitors nimesulide and NS-398
      at inhibiting granuloma dry weight, vascularity and COX activity.

PMID- 9535547
TI  - What can we expect from subtype 2 angiotensin receptors (AT2)? [ comment].

PMID- 9535548
TI  - Regulation of the immune response by macrophage migration inhibitory factor:
      biological and structural features.
AB  - The classical T cell cytokine macrophage migration inhibitory factor (MIF) has
      reemerged recently as a critical mediator of the host immune and stress response.
      MIF has been found to be a mediator of several diseases including gram-negative
      septic shock and delayed-type hypersensitivity reactions. Its immunological
      functions include the modulation of the host macrophage and T and B cell
      response. In contrast to other known cytokines, MIF production is induced rather
      than suppressed by glucocorticoids, and MIF has been found to override the
      immunosuppressive effects of glucocorticoids. Recently, elucidation of the three
      dimensional structure of MIF revealed that MIF has a novel, unique cytokine
      structure. Here the biological role of MIF is reviewed in view of its distinct
      immunological and structural properties.

PMID- 9535549
TI  - Maternal malaria and parasite adhesion.
AB  - Malaria during pregnancy continues to be a major health problem in endemic
      countries, with clinical consequences, including death, for both mother and
      child. Just as cerebral malaria results from parasite sequestration in the brain,
      maternal malaria results from parasite sequestration in the placenta, and a
      distinct subpopulation of parasites which bind chondroitin sulfate A but not CD36
      causes the syndrome. Women have little or no immunological experience with this
      parasite prior to first pregnancy, making primigravid women particularly
      vulnerable to infection. Parasites adhere to the surface of trophoblastic villi,
      eliciting the accumulation of inflammatory leukocytes in the intervillous space,
      and the necrosis of adjacent placental tissue. Maternal malaria results in poor
      pregnancy outcomes, although the responsible mechanisms have not been defined. In
      holoendemic areas both placental infection and poor outcome decrease in frequency
      with successive pregnancies; protection may result from control of parasite
      adhesion, suggesting an attractive target for new therapies.

PMID- 9535550
TI  - Regulation of podocyte structure during the development of nephrotic syndrome.
AB  - Nephrotic syndrome is a common kidney disease seen in both children and adults.
      The clinical syndrome includes massive proteinuria, hypoalbuminemia, edema, and
      usually hypercholesterolemia. Development of these clinical changes is closely
      correlated with profound structural changes in glomerular epithelial cells, or
      podocytes, which together with the glomerular basement membrane and endothelium
      comprise the kidney's blood filtration barrier. Although relatively little is
      known about the cellular or molecular changes which occur within podocytes during
      the development of nephrotic syndrome, cytoskeletal proteins very likely play a
      central role in these changes since they are primarily responsible for the
      maintenance of cell structure in almost all cells. This review focuses on: (a)
      the structure and function of podocytes in both the normal state and during
      nephrotic syndrome and (b) the potential roles of several cytoskeleton-associated
      proteins identified in podocytes in the development of and/or recovery from the
      pathophysiological cytoskeletal changes which occur in podocytes during nephrotic
      syndrome.

PMID- 9535551
TI  - Retrovirus-mediated gene transfer into human hematopoietic stem cells.
AB  - Human hematopoietic stem cells genetically modified by retroviral-mediated gene
      transfer may offer new treatment options for patients with genetic disease. The
      potential of gene-modified hematopoietic stem cells as vehicles for gene delivery
      was first illustrated by the demonstration that hematopoietic systems of lethally
      irradiated mice can be reconstituted with retroviral vector transduced syngeneic
      bone marrow, and that these cells can in turn provide genetically marked progeny
      which persist in blood and marrow over extended time periods. In contrast,
      hematopoietic stem cells from large animals prove difficult to transduce with
      retroviral vectors and are consequently less likely to function as vehicles for
      long-term gene therapy. Indeed, clinically relevant levels of gene transfer into
      large animal and human hematopoietic stem cells has not been widely achieved. The
      need for improved retroviral vector systems and for understanding the biology of
      hematopoietic stem cell gene transfer continue to fuel intense research activity.
      Preliminary results from human stem cell gene marking and gene therapy trials
      currently underway are encouraging. This contribution reviews the underlying
      concepts relevant to retroviral-mediated gene transfer into hematopoietic stem
      cells. We survey the evolution of approaches for gene transfer into hematopoietic
      stem cells, from murine and large animal models to the first human clinical
      trials. Finally, we discuss new strategies which are currently being pursued.

PMID- 9535552
TI  - Functional correlates of nicotine administration: similarity with drugs of abuse.
AB  - Changes in the local utilization of cerebral glucose resulting from administered
      drugs acting on the central nervous system can be evaluated quantitatively by the
      [14C]2-deoxyglucose method. We report the findings obtained by the [14C]2
      deoxyglucose method that contribute to understanding the cerebral functional
      effects of drugs of abuse and discuss in particular the similarities between
      nicotine and other addictive drugs. A common consequence of the intravenous
      administration of psychomotor stimulants and opioids in the rat is the increase
      in glucose utilization in the shell of nucleus accumbens. This functional change
      is accompanied by increased local extracellular concentrations of dopamine.
      Altered functional activity and dopamine neurotransmission in the shell of the
      nucleus accumbens thus represent distinctive neurobiological markers of the
      addictive properties of several drugs, independently of the specific
      neurochemical mechanisms of action. It has recently been shown that the
      intravenous administration of a pulse of nicotine, at single-unit doses
      corresponding to those that maintain self-administration in the rat, produces
      neurochemical and metabolic changes in the shell of the nucleus accumbens that
      closely resemble those of psychomotor stimulants and opioids. The latter results
      demonstrate that nicotine shares with highly addictive drugs a distinct
      neurochemical and functional consequence. They therefore contribute to the
      neurochemical definition of the addictive nature of nicotine. These neurochemical
      and functional changes may contribute to the changes in expression of
      intracellular second messengers and neurotransmitter/receptor systems observed
      particularly in the shell following the administration of drugs of abuse.

PMID- 9535553
TI  - Repression of c-fos and c-jun gene expression is not part of AT2 receptor coupled
      signal transduction.
AB  - The signal transduction mechanism coupled to angiotensin AT2 receptors is still a
      matter of debate. Based on the findings that AT2 receptor stimulation causes
      inhibition of proliferation, and that other antiproliferative agents such as
      transforming growth factor-beta, retinoic acid, and MyoD act via repression of
      immediate early gene (IEG) expression, this study was aimed at elucidating
      whether downregulation of IEG expression is also part of the AT2 receptor coupled
      signaling mechanism. Stimulation of angiotensin AT2 receptors in the rat
      pheochromocytoma cell line PC12 W following pretreatment with growth factors was
      able to counteract growth factor induced proliferation but not to repress growth
      factor induced c-fos and c-jun expression; neither did AT2 receptor stimulation
      cause an induction of c-fos expression. We conclude that, in contrast to other
      growth-inhibiting agents, the antiproliferative effect of angiotensin II via the
      AT2 receptor is not mediated by repression of the immediate early genes c-fos and
      c-jun.

PMID- 9535554
TI  - Identification of two novel mutations in the ventricular regulatory myosin light
      chain gene (MYL2) associated with familial and classical forms of hypertrophic
      cardiomyopathy.
AB  - Five disease genes encoding sarcomeric proteins and associated with familial and
      classical forms of hypertrophic cardiomyopathy have been determined since 1989.
      In 1996 two other genes encoding ventricular regulatory and essential myosin
      light chains were shown to be associated with a particular phenotype of the
      disease characterized by mid left ventricular obstruction. The aim of the present
      study was to search for mutations in the ventricular regulatory myosin light
      chain gene (MYL2), located on chromosome 12q23q24.3, in a panel of 42 probands
      presenting a classical phenotype of familial hypertrophic cardiomyopathy. Single
      strand conformation polymorphism analysis was used to search for mutations in the
      coding segments of the MYL2 gene, and the abnormal products were sequenced. Two
      novel missense mutations, Phe18Leu in exon 2 and Arg58Gln in exon 4 were
      identified in three unrelated families. None of the affected patients had
      hypertrophy localized only at the level of the papillary muscle with mid left
      ventricular obstruction. By analysis of genetic recombinations, one of these
      mutations identified in a large family allowed us to refine the localization of
      the MYL2 gene on the genetic map, in an interval of 6 cM containing six
      informative microsatellite markers. In conclusion, we show that mutations in the
      MYL2 gene may be involved in familial and classical forms of hypertrophic
      cardiomyopathy, and we provide new tools for the genetic analysis of patients
      with familial hypertrophic cardiomyopathy.

PMID- 9535555
TI  - Immunotherapy of acute lymphoblastic leukemia by vaccination with autologous
      leukemic cells transfected with a cDNA expression plasmid coding for an
      allogeneic HLA class I antigen combined with interleukin-2 treatment.

PMID- 9535556
TI  - Diseases of the extracellular matrix.

PMID- 9535557
TI  - Genetic diseases of the extracellular matrix: more than just connective tissue
      disorders.
AB  - The rapidly increasing knowledge about the molecular biology of the extracellular
      matrix has changed the concepts for the pathomechanisms of heritable connective
      tissue diseases. The spectrum of genetic matrix disorders is much broader than
      previously thought and now also includes diseases of organs such as the kidney,
      eye, and muscles. In addition, evidence is emerging that certain "acquired"
      diseases may be inherited, and that defects in signal transduction and patterning
      genes contribute to the pathology of connective tissue disorders. The phenotypes
      of genetic matrix disorders are determined by basic biological characteristics of
      the extracellular matrix. (a) The extracellular matrix occurs ubiquitously and is
      important for organ development and functions. (b) Matrix macromolecules are
      often large oligomers that polymerize into suprastructures at several hierarchic
      levels. They form insoluble fibrils or filaments that are further assembled into
      tissue suprastructures, for example, bundles or networks of fibrils. (c) Matrix
      suprastructures share characteristics with metal alloys. Tissue-specific mixtures
      of matrix molecules form specific arrays that differ from those of the pure
      components. Therefore the phenotypes of matrix diseases reflect a cascade of
      pathological events disturbing alloy formation, such as abnormal protein
      synthesis and folding, defective fibrillogenesis, and bundling, all capable of
      leading to abnormal cell-matrix interactions.

PMID- 9535558
TI  - Mouse models for extracellular matrix diseases.
AB  - Mutations of a number of genes encoding for extracellular matrix (ECM) proteins
      in mice have provided new insights regarding their role during development and
      disease. Many mouse strains have helped to verify the link between mutation and
      disease in humans, and others have produced unexpected phenotypes and identified
      new functions for ECM proteins. Finally, some null mutations in ECM genes provide
      no phenotypic alterations in mice, confronting the scientific community with a
      new challenge to search for their functions. This review lists all mouse strains
      with spontaneous and experimentally induced mutations in ECM genes. The
      phenotypes of these mice are discussed in comparison with the human diseases.

PMID- 9535559
TI  - Structure and biological activity of the extracellular matrix.
AB  - The extracellular matrix is formed by complex and intricate networks within which
      molecules are precisely organized. These molecular networks determine the
      specific histoarchitecture of tissues and provide cells with information and a
      scaffold. Most of the structural extracellular matrix molecules - collagens,
      noncollagenous glycoproteins, and proteoglycans - are chimeric and share common
      domains. Studies of the interactions between extracellular matrix molecules and
      mapping of the interaction sites to defined structural modules have led to the
      concept that the function of the extracellular matrix relies largely in the
      polymers that they form. Furthermore, determination of the tertiary structure of
      protein motifs involved either in the assembly of the various molecules into
      polymers or in cell-extracellular matrix interactions has recently opened the
      field of structural biology of the extracellular matrix.

PMID- 9535560
TI  - Pathogenesis of fibrosis: type 1 collagen and the skin.
AB  - This review on the pathogenesis of fibrosis emphasizes the similarities between
      tissue repair, a tightly regulated salutary biological response, and fibrosis, an
      unregulated pathological process. It focuses on the transcriptional regulation of
      type I collagen, the role of cytokines in fibroblast activation, integrins as
      examples of cell-matrix signaling pathways, and the heterogeneity of fibroblast
      populations as factors contributing to fibrosis. Tissue remodeling and the role
      of matrix metalloproteinases and metalloproteinase inhibitors are mentioned
      briefly. The capacity of extracellular matrix to modulate cellular function is a
      recurring theme.

PMID- 9535561
TI  - The cartilage collagens: a review of their structure, organization, and role in
      the pathogenesis of experimental arthritis in animals and in human rheumatic
      disease.
AB  - This contribution reviews the structure and organization of collagen molecules
      found in cartilage and the roles that they may play in rheumatic diseases.
      Cartilage is unique in its physical properties and molecular composition, and
      contains sufficient amounts of types II, IX, X, and XI collagen to deem these
      molecules as "cartilage-specific." The vitreous body of the eye, a "cartilage
      like" tissue is also rich in the same collagens but is type X deficient. Types VI
      and XII collagen are present in cartilage as well as noncartilaginous tissues.
      Types II, IX, and XI collagen are organized into matrix fibrils, where type II
      constitutes the bulk of the fibril, type XI regulates fibril size, and type IX
      facilitates fibril interaction with proteoglycan macromolecules. Genetic defects
      in these collagens can produce mild to severe developmental abnormalities,
      including spondyloepiphyseal dysplasia often accompanied by an accelerated form
      of osteoarthritis. Sensitization with collagen can produce experimental rheumatic
      diseases. Type II collagen induces an erosive polyarthritis in certain strains of
      rats, mice, and higher primates which can resemble rheumatoid arthritis and
      relapsing polychondritis. Type XI collagen is arthritogenic in rats but not mice;
      type IX induces autoimmunity in both species but not arthritis. Arthritis is
      initiated by complement fixing antibodies that bind to type II collagen in
      autologous cartilage, and the production of these antibodies is MHC restricted
      and T cell dependent. It is unclear whether T cells alone can induce arthritis,
      although they probably help sustain it. Mapping and characterizing the of T cell
      epitopes on type II collagen has resulted in the synthesis of small homolog and
      substituted peptides of type II collagen which suppress arthritis in an antigen
      specific manner by a variety of routes, including mucosal. Moreover, collagen
      induced arthritis has proven a valuable model to study the contribution of
      cytokines and other biological agents in the pathogenesis of joint injury and how
      they might be used to develop new therapies. Collagen autoimmunity has been
      implicated in the pathogenesis rheumatoid arthritis and polychondritis.
      Circulating antibodies to type II collagen are found in both diseases. Antibodies
      to types IX and XI collagen are also present in rheumatoid sera but are less
      prevalent. Rheumatoid cartilage and synovium contain antibodies to type II
      collagen at a prevalence far greater than serum, suggesting an intra-articular
      antigen-driven immune process. Although effective in animal models, attempts to
      treat rheumatoid arthritis with orally administered type II collagen have proven
      elusive. Different approaches using newer formulations and selected or modified
      oligopeptides remain to be tested and could prove effective in the treatment of
      the human rheumatic diseases.

PMID- 9535562
TI  - Aspiration lesions of the amygdala disrupt the rhinal corticothalamic projection
      system in rhesus monkeys.
AB  - In macaque monkeys, aspiration but not excitotoxic lesions of the medial temporal
      lobe limbic structures, the amygdala and hippocampus, produce a severe impairment
      in visual recognition memory. Furthermore, certain ventromedial cortical regions,
      namely the rhinal (i.e., entorhinal and perirhinal) cortex, are now known to be
      critical for visual recognition memory. Because the route taken by temporal
      cortical efferent fibers, especially perirhinal efferents, passes nearby the
      amygdala, it is possible that inadvertent damage to these fibers is produced by
      the aspirative but not the excitotoxic process, thereby accounting at least in
      part for the different behavioral outcomes of the two types of lesion. To test
      this idea, we assessed the integrity of the rhinal corticothalamic projection
      system after aspiration lesions of the amygdala. Three rhesus monkeys with
      unilateral amygdala removals received bilaterally symmetrical injections of a
      retrograde fluorescent tracer into the medial portion of the mediodorsal nucleus
      of the thalamus. Retrogradely labeled cells were identified using conventional
      fluorescence microscopy techniques. In all three cases, the rhinal cortex of the
      intact hemispheres contained moderate numbers of retrogradely labeled cells. By
      contrast, the rhinal cortex of the amygdalectomized hemispheres consistently
      contained few retrogradely labeled cells, and a direct comparison of the two
      hemispheres showed this difference to be statistically significant. A similar
      asymmetric pattern was observed for area TE but not for the cortex lining the
      dorsal bank of the superior temporal sulcus, nor for the rostral cingulate motor
      area, which was examined as a control. The results indicate that aspiration
      lesions of the amygdala not only remove the cell bodies of the amygdala, as
      intended, but also inadvertently disrupt projection fibers arising from cells in
      the rhinal cortex and area TE that pass nearby or through the amygdala en route
      to the thalamus. Behavioral studies examining the effects of aspiration lesions
      of the amygdala in nonhuman primates need to take these findings into
      consideration.

PMID- 9535563
TI  - Control of reactive balance adjustments in perturbed human walking: roles of
      proximal and distal postural muscle activity.
AB  - Studies on the proactive control of gait have shown that proximal (hip/trunk)
      muscles are the primary contributors to balance control, while studies on
      reactive balance control during perturbed gait, examining only activity in distal
      (leg/thigh) muscles, have shown that these muscles are important in compensating
      for a gait disturbance. This study tested the hypothesis that proximal muscles
      are also primary contributors to reactive balance control during perturbed gait.
      Thirty-three young adults participated in a study in which an anterior slip was
      simulated at heel strike by the forward displacement of a force plate on which
      they walked. Surface electromyographic data were recorded from bilateral leg,
      thigh, hip and trunk muscles. Kinematic data were collected on joint angle
      changes in response to the perturbation. The results did not support the
      hypothesis that the proximal muscles contribute significantly to balance control
      during perturbed gait. The proximal muscles did not demonstrate more consistent
      activation, earlier onset latency, longer burst duration or larger burst
      magnitude than distal muscles. Moreover, although proximal postural activity was
      often present in the first slip trial, it tended to adapt away in later trials.
      By contrast, the typical postural responses exhibited by young adults consisted
      of an early (90-140 ms), high-magnitude (4-9 times muscle activity during normal
      walking) and relatively long duration (70-200 ms) activation of bilateral
      anterior leg muscles as well as the anterior and posterior thigh muscles. Thus,
      postural activity from bilateral leg and thigh muscles and the coordination
      between the two lower extremities were the key to reactive balance control and
      were sufficient for regaining balance within one gait cycle. The adaptive
      attenuation of proximal postural activity over repeated trials suggests that the
      nervous system overcompensates for a novel balance threat in the first slip trial
      and fine-tunes its responses with experience.

PMID- 9535564
TI  - Local changes in GTP-binding protein immunoreactivities in human epileptogenic
      neocortex.
AB  - The relative levels of guanine nucleotide-binding protein alpha-subunits
      Gi1alpha, Gi2alpha, Gi3alpha, Go(alpha), Gs(alpha), and Gx/z(alpha) were measured
      in neocortex removed at surgery from patients with intractable temporal lobe
      epilepsy. Immunoreactivity was quantified using specific polyclonal antisera
      against the Galpha-subunits according to the Laurell "rocket"
      immunoelectrophoresis technique. We compared the G protein contents of spiking
      (active) and nonspiking (nonactive) cortical regions, based on intraoperative
      electrocorticography, within the same and different patients. There were no clear
      trends for lower or higher levels of G-protein subtypes to be found in the
      samples of protein extracts from nonspiking regions as compared to spiking
      regions. However, comparison of paired samples of spiking and nonspiking cortex
      within the same patient demonstrated that levels of certain G-protein subtypes
      were either increased or decreased in all patients. This indicates that cortical
      regions with enhanced neuronal activity may produce microzonal alterations in the
      levels of G proteins. Moreover, our results suggest that high levels of Gi1alpha
      and low levels of the other G-protein subtypes appear to be associated with a
      greater susceptibility to maintaining spiking activity.

PMID- 9535565
TI  - Neuropeptide FF in the lateral spinal and lateral cervical nuclei: evidence of
      contacts on spinothalamic neurons.
AB  - Neuropeptide FF (NPFF, F8Famide) is best known for its modulating effect on
      opioid analgesia and morphine tolerance. However, the exact mode of action of
      NPFF in sensory transmission is not known. We compared the distribution of NPFF
      immunoreactive (ir) fibers and terminal-like thickenings with the retrograde,
      tracer-filled spinothalamic (ST) neurons in the lateral spinal nucleus (LSN) and
      lateral cervical nucleus (LCN) of rat, areas where NPFF-containing nerve
      terminals are abundant. We injected fluorescent latex microspheres into the
      ventroposterolateral thalamic nucleus and more medial thalamic nuclei, which are
      innervated by ST neurons. We found NPFF-ir terminal-like thickenings and fibers
      apposing the tracer-filled neurons in the LSN and LCN. ST neurons filled with the
      retrograde tracer making contacts with NPFF-ir terminal-like thickenings, were
      found to terminate not only in the ventroposterolateral thalamic nucleus but also
      in more medial thalamic nuclei. The highest number of tracer-filled ST neurons
      having NPFF-ir terminal-like thickenings and fibers in apposition were found at
      the cervical level. Our results suggest that NPFF-containing systems in the
      spinal cord of rat are not limited to the substantia gelatinosa, and the sensory
      functions of NPFF may be mediated at least partly through the modulation of the
      ST system. NPFF-ir contacts in the LSN and LCN might play an important role in
      the somatic sensory transmission system. This study shows evidence for the first
      time that the spinal NPFF-containing system may be involved in mechanisms that
      control sensory input to the supraspinal levels.

PMID- 9535566
TI  - Involvement of the locus coeruleus in analgesic effects of a low dose of naloxone
      during the inflammatory process.
AB  - We evaluated the effects of systemic administration of a low dose of naloxone in
      rats with bilateral lesions in the area of the locus coeruleus (LC) under
      conditions of unilateral inflammation, compared with those in sham-operated rats.
      In each group, rats received a single s.c. injection of carrageenan (6 mg in 0.15
      ml saline), and effects of a low dose of naloxone (5 microg/kg, i.p.) on thermal
      nociception were examined at 4 h and 7 days following the induction of unilateral
      hindpaw inflammation. The antinociceptive effect was assessed by prolongation of
      the paw withdrawal latency (PWL) to noxious thermal stimuli. Prior to induction
      of inflammation, the low dose of naloxone had no significant effect on PWLs in
      either the sham-operated or the LC-lesioned rats. Four hours after carrageenan
      injection, the low dose of naloxone produced prolongation of PWLs in the sham
      operated rats but failed to induce antinociception in the LC-lesioned rats.
      Antinociceptive effects were observed in both groups of rats 7 days after
      carrageenan injection. These results suggest that the LC is involved in naloxone
      induced anti-nociception during the early phase of inflammation.

PMID- 9535567
TI  - Afferent feedback in the triphasic EMG pattern of leg muscles associated with
      rapid body sway.
AB  - Electromyographic (EMG) patterns of leg muscles associated with rapid body sway
      were studied in relation to displacement of the center of foot pressure (CFP).
      Standing subjects were instructed to shift the CFP by swaying their bodies,
      pivoting at the ankle as rapidly and accurately as possible after an auditory
      signal. CFP position was designated as N when the subject maintained a relaxed
      bending posture and as F when a maximally forward-leaning posture was maintained.
      A serial, stereotyped triphasic EMG pattern was observed in the rapid shift of
      CFP from N to F: cessation of EMG activity in the gastrocnemius (GC) muscle was
      followed by a burst in the tibialis anterior (TA) muscle (acceleration phase),
      and then resumed discharge occurred in the GC muscle with cessation of activity
      in the TA muscle (deceleration and stop). When the subject shifted the CFP from N
      to F to different degrees, the duration and amount of EMG activity in the TA
      muscle during acceleration and the GC muscle in deceleration were proportionate
      to the amount of CFP displacement associated with forward body sway. To determine
      the functional roles of sensory inputs from the foot on the triphasic EMG
      pattern, body sway was studied under the condition of sensory block in the feet
      induced by ischemia from tourniquets placed bilaterally just above the ankle
      joints. The triphasic EMG pattern persisted during ischemia. The time of GC
      cessation and the onset of TA burst at acceleration remained unchanged, but the
      times of TA cessation and resumption of GC discharge at deceleration were altered
      during ischemia. Moreover, subjects were unable to stop at F and eventually fell.
      These results indicate that both amount and duration of EMG activity associated
      with rapid body sway are functions of the amount of CFP displacement. Somatic
      sensation from the feet is important for control of burst and cessation timing
      and duration in leg muscle activity.

PMID- 9535568
TI  - The relationship between monkey dentate cerebellar nucleus activity and kinematic
      parameters of wrist movement.
AB  - Extracellular single-unit recordings were made from cerebellar dentate neurones
      in two conscious monkeys trained to perform wrist flexion and extension movement
      tasks that produced a range of static joint positions and dynamic velocities. The
      experiment was designed to establish whether there is a relationship between the
      discharge of dentate neurones and movement kinematics. The discharge patterns of
      58 "wrist-related" neurones were correlated with joint position, duration of
      unidirectional movement (referred to as duration of velocity) and amplitude of
      velocity (peak velocity). Significant (P<0.05) correlations were found between
      the level of tonic discharge and static joint position in 21 of 58 (36%)
      neurones. Correlations between phasic discharge and at least one of the velocity
      variables were found in 17 of 43 (40%) neurones [7 of 43 (16%) showed a
      correlation between the duration of phasic excitation associated with movement
      and duration of velocity, 5 of 43 (12%) between the peak rate of phasic
      excitation and peak velocity and 10 of 43 (23%) between the number of discharges
      in the period of phasic excitation and peak velocity]. We conclude (for reasons
      outlined in the Discussion) that there is not a strong relationship between
      neuronal discharge and kinematic parameters of wrist movement in the dentate
      nucleus.

PMID- 9535569
TI  - Changes in the mRNA expression pattern, with special reference to calcitonin gene
      related peptide, after axonal injuries in rat motoneurons depends on age and type
      of injury.
AB  - The axotomy reaction in motoneurons after a peripheral nerve transection in the
      adult animal is characterized by a robust upregulation of alpha-calcitonin gene
      related peptide (CGRP) messenger RNA (mRNA) together with mRNAs encoding
      cytoskeletal and growth-related proteins. Here we have examined whether the
      nature of the lesion and the age of the animal have any impact on the mRNA
      regulation in severed cells. Thus, the effect of a sciatic nerve transection in
      the adult rat was compared with, on the one hand, ventral root avulsions in the
      adult animal and, on the other hand, sciatic nerve transection in the immature
      animal. In the two latter cases, a proportion of the lesioned cells die and
      overall chances of regeneration are small. In the adult animal a sciatic nerve
      transection induced an upregulation of alpha-CGRP mRNA from the 3rd day after
      surgery and throughout the first 3 weeks (the time span of the study). Also low
      affinity nerve growth factor receptor (p75) and growth-associated protein-43 (GAP
      43) mRNAs were upregulated during the entire 3-week period. In contrast, after
      ventral root avulsion, the expression of alpha-CGRP, c-jun, and p75 mRNAs were
      normalized within the 1st postoperative week, while GAP-43 mRNA was still
      upregulated at 3 weeks. Galanin message-associated peptide (GMAP) mRNA became
      upregulated preferentially in motoneurons subjected to ventral root avulsion,
      while nitric oxide synthase (NOS) mRNA was expressed exclusively after the latter
      type of injury. In the immature animal, alpha-CGRP mRNA was downregulated after
      sciatic nerve transection in rats aged 3 days or 7 days at the time of surgery;
      while, in contrast, an upregulation was seen in 12- or 21-day-old animals. GAP-43
      and c-jun mRNAs were upregulated in lesioned motoneurons of all ages, while GMAP
      mRNA was upregulated preferentially in lesioned motoneurons of early postnatal
      animals. p75 mRNA was expressed in unlesioned immature motoneurons until the age
      of 7-10 days. The downregulation of p75 mRNA in intact cells at this age
      coincided with a developmental switch in the ability of axotomized cells to
      express increased levels of p75 mRNA. No expression of NOS mRNA was detectable in
      lesioned cells of any of the age groups. These results show that the age of the
      animal and the type of axonal injury are indeed to a high degree influencing the
      changes seen in the protein expression pattern in axotomized rat motoneurons. The
      different responses in these paradigms suggest differences in the trophic
      response from surrounding glia or the trophic responsiveness of lesioned
      motoneurons. Also, the results may indicate different roles for the studied
      substances during the regenerative response of lesioned neurons. Of the
      substances studied here, upregulation of alpha-CGRP and p75 mRNAs best correlated
      with a possibility of axon regeneration.

PMID- 9535570
TI  - Cortical reorganization and phantom phenomena in congenital and traumatic upper
      extremity amputees.
AB  - The relationship between phantom limb phenomena and cortical reorganization was
      examined in five subjects with congenital absence of an upper limb and nine
      traumatic amputees. Neuromagnetic source imaging revealed minimal reorganization
      of primary somatosensory cortex in the congenital amputees (M=0.69 cm, SD 0.24)
      and the traumatic amputees without phantom limb pain (M=0.27 cm, SD 0.25); the
      amputees with phantom limb pain showed massive cortical reorganization (M=2.22
      cm, SD 0.78). Phantom limb pain and nonpainful phantom limb phenomena were absent
      in the congenital amputees. Whereas phantom limb pain was positively related to
      cortical reorganization (r=0.87), nonpainful phantom phenomena were not
      significantly correlated with cortical reorganization (r=0.34). Sensory
      discrimination was normal and mislocalization (referral of stimulation-induced
      sensation to a phantom limb) was absent in the congenital amputees. The role of
      peripheral and central factors in the understanding of phantom limb pain and
      phantom limb phenomena is discussed in view of these findings.

PMID- 9535571
TI  - Adaptive variations of undulatory behaviors in larval lamprey: comparison of
      swimming and burrowing.
AB  - In larval lamprey, movements and muscle activity during swimming and burrowing
      behaviors were compared. Burrowing consisted of two components: an initial
      component in which the head was driven into the burrowing medium; and a final
      component in which the animal pulled the rest of its body into the burrowing
      medium. The initial component of burrowing was characterized by large undulatory
      movements and rhythmic muscle burst activity that were similar in form to those
      during fast swimming, but more intense. During the initial component of
      burrrowing, burst durations, burst amplitudes, and burst proportions of motor
      activity were larger than those during swimming, while cycle time was slightly
      shorter than during swimming. Intersegmental phase lags and right-left phase
      values were similar for swimming and initial burrowing. The final component of
      burrowing was characterized by sharp, long-duration flexures on one side of the
      body, sometimes followed by similar flexures on the other side. Each flexure was
      produced by long-duration, large-amplitude muscle burst activity on the same side
      of the body or several shorter sequential bursts with slightly smaller
      amplitudes. During the final component of burrowing, burst durations and burst
      amplitudes of motor activity were much larger than those during swimming or
      during the initial component of burrowing. It is suggested that the motor
      patterns for swimming and the initial component of burrowing are produced by a
      common spinal locomotor network. The final component of burrowing may use some of
      the same neurons in the spinal locomotor networks, but the networks are probably
      configured differently than the situation during swimming.

PMID- 9535572
TI  - Task-dependent mixtures of coordinate systems in visuomotor transformations.
AB  - In two experiments the involvement of relative and fixed coordinate systems in
      visuomotor transformations was examined. The experimental task required the
      successive performance of two movements in each trial, which had to "correspond"
      to different visual stimuli. One kind of visual display indicated target
      positions by way of different horizontal positions of a vertical line on a
      monitor (position mode), while the other indicated movement amplitudes by way of
      different lengths of a horizontal line (amplitude mode). Formal analysis of
      variances and covariances of successive individual movements led to the
      conclusion that in the position mode visuomotor transformations were based on a
      mixture of relative and fixed coordinate systems, while in the amplitude mode
      only a relative coordinate system was involved. Thus, visuomotor transformations
      can be characterized as mixtures of different coordinate systems, and their
      respective weights in the mixtures are task-dependent.

PMID- 9535573
TI  - Group III metabotropic glutamate receptor agonists modulate high voltage
      activated Ca2+ currents in pyramidal neurons of the adult rat.
AB  - In pyramidal neurons of the rat sensorimotor cortex, we have investigated the
      modulation of high voltage-activated calcium currents by agonists at group III
      metabotropic glutamate receptors (mGluRs). l-2-Amino-4-phosphonobutyrate (l-AP4)
      and l-serine-O-phosphate (l-SOP) reduced calcium currents in the vast majority of
      cells isolated from the adult animal. Interestingly, this modulation was
      negligible in the young animals (2-14 postnatal days), becoming prominent only
      after full development (more than 21 days). The efficacy of l-SOP mimicked l-AP4
      in reducing calcium currents. Yet, l-SOP produced saturating responses at about 3
      microM and significant modulation at nanomolar concentrations (EC50=923 nM). The
      voltage-dependence of the group III mGluR-mediated responses was evaluated by
      comparing the inhibition of "standard" and "facilitated" conductances. On the
      calcium currents facilitated by depolarizing prepulse, 3 microM l-SOP produced a
      mean 13.4% inhibition compared with 19.6% in control condition, supporting the
      proposition that part of the inodulation was voltage-dependent. The calcium
      current inhibition caused by the activation of group III metabotropic glutamate
      receptors was only partially sensitive to omega-conotoxin GVIA, but largely
      inhibited by omega-agatoxin IVA, at concentrations (100 nM) known to block P- and
      Q-type channels. Conversely, the dihydropyridine antagonists nifedipine and
      nimodipine (50-500 nM) failed to prevent the group III mGluR-mediated response in
      the majority of tested cells (more than 65%). Furthermore, the long-lasting tail
      promoted by the inclusion of the dihydropyridine agonist Bay K 8644 was not
      consistently affected by l-SOP and l-AP4. These findings imply that the observed
      modulation involves different channel subtypes, namely N- and P- or Q-type
      channels, and suggests that group III mGluRs play an important role in the
      intrinsic and synaptic functions of adult cortical pyramidal neurons.

PMID- 9535574
TI  - Expression of platelet-derived growth factor after intrastriatal ibotenic acid
      injury.
AB  - The expression of platelet-derived growth factor (PDGF) was studied in a rat
      model of Huntington's disease, produced by unilateral intrastriatal ibotenic acid
      injections. The most pronounced effect registered was that the number of PDGF
      immunoreactive cells increased in the lesioned area up to 10 weeks after the
      surgery. Double immunofluorescence staining indicated that the PDGF-positive
      cells were astrocytes. The increased PDGF immunoreactivity was associated with
      only minor changes in total PDGF mRNA and PDGF protein levels in the lesioned
      area. Reverse transcription-polymerase chain reaction (RT-PCR) demonstrated a
      slight increase in PDGF mRNA after ibotenic acid lesion, but this was not
      reflected in an increase in PDGF A- and B-chain protein concentration as measured
      with ELISA. After sham operation an increase in PDGF protein concentration was
      seen, while the number of PDGF-immunoreactive cells was unchanged. The
      accumulation of PDGF in the astrocytes might reflect the role of PDGF in a repair
      process in neurodegenerative processes.

PMID- 9535575
TI  - Context-dependent reflex control: some insights into the role of balance.
AB  - Recent research suggests that the balance requirements of a task dictate the
      reflexive response. However, these observations were inferred indirectly from
      either different tasks or different phases of the same task. This study directly
      tested the hypothesis of balance-dependent control during recovery from an
      unexpected trip. The subjects were tripped in two different support conditions:
      unilimb support (provided by the stance limb) or trilimb support (provided by the
      stance limb and both arms placed on adjacent parallel bars). The subjects
      exhibited anticipatory changes: they biased the body center of mass toward the
      support limb in the mediolateral direction and elevated the swing limb higher
      when there was a possibility of being tripped. The electromyographic (EMG)
      latencies were not influenced by the threat to equilibrium. The magnitudes of the
      EMG reflexive response to the trip were clearly modulated as a function of the
      threat to stability, not in a simple manner, but rather in a complex manner,
      which optimized the recovery strategy. It is evident that the overriding concern,
      equilibrium control during locomotion, has a dominant influence on reflex
      modulation.

PMID- 9535576
TI  - Anxiolytic-like behavior after lesion of the tuberomammillary nucleus E2-region.
AB  - The tuberomammillary nucleus (TM), located in the posterior hypothalamic region,
      consists of five subgroups and is the only known source of brain histamine. In
      the present experiment, rats received bilateral ibotenic acid or sham lesions in
      the rostroventral part of the TM (E2-region). Three weeks later they were tested
      on the elevated plus-maze test of fear and anxiety. Lesions in the
      tuberomammillary E2-region elevated the time spent on the open arms, as well as
      excursions into the end of the open arms, increased scanning over the edge of an
      open arm, and decreased risk-assessment from an enclosed arm. Thus, partial
      destruction of TM intrinsic neurons can induce anxiolytic-like effects which are
      possibly related to a lesion-induced reduction of histaminergic activity.

PMID- 9535577
TI  - Magnetic transcranial stimulation at intensities below active motor threshold
      activates intracortical inhibitory circuits.
AB  - A magnetic transcranial conditioning stimulus given over the motor cortex at
      intensities below threshold for obtaining electromyographical (EMG) responses in
      active hand muscles can suppress responses evoked in the same muscles at rest by
      a suprathreshold magnetic test stimulus given 1-5 ms later. In order to define
      the mechanism of this inhibitory effect, we recorded descending volleys produced
      by single and paired magnetic transcranial stimulation of motor cortex through
      high cervical, epidural electrodes implanted for pain relief in two conscious
      subjects with no abnormality of the central nervous system. The conditioning
      stimulus evoked no recognisable descending activity in the spinal cord, whilst
      the test stimulus evoked 3-4 waves of activity (I-waves). Conditioning
      stimulation suppressed the size of both the descending spinal cord volleys and
      the EMG responses evoked by the test stimulus. Inhibition of the descending
      spinal volleys was most pronounced at ISI 1 ms and had disappeared by ISI 5 ms.
      It was evident for all components following the I1-wave, while the I1-wave itself
      was not inhibited at all. We conclude that a small conditioning magnetic stimulus
      can suppress the excitability of human motor cortex, probably by activating local
      corticocortical inhibitory circuits.

PMID- 9535578
TI  - Adrenal medulla and exercise training.
AB  - The adrenaline release from the adrenal medulla increases during exercise, but at
      a given absolute work intensity the magnitude of this response is less pronounced
      in endurance trained vs sedentary individuals most likely due to a lower
      sympathetic stimulation of the adrenal medulla. However, when trained and
      untrained subjects are compared at identical relative work loads as well as in
      response to numerous non-exercise stimuli. endurance trained athletes have a
      higher epinephrine secretion capacity compared to sedentary individuals. This
      indicates a development of a so-called "sports adrenal medulla" as a result of a
      long term adaptation of an endocrine gland to physical training. Such an
      adaptation is parallel to adaptations taking place in other tissues like skeletal
      muscle and the heart. and can be advantageous in relation to both exercise
      performance in the competing athlete and cause a biological rejuvenation in
      relation to aging.

PMID- 9535579
TI  - Re-interpreting anaerobic metabolism: an argument for the application of both
      anaerobic glycolysis and excess post-exercise oxygen comsumption (EPOC) as
      independent sources of energy expenditure.
AB  - Due to current technical difficulties and changing cellular conditions, the
      measurement of anaerobic and recovery energy expenditure remains elusive. During
      rest and low-intensity steady-state exercise, indirect calorimetric measurements
      successfully represent energy expenditure. The same steady-state O2 uptake
      methods are often used to describe the O2 deficit and excess post-oxygen
      consumption (EPOC): 1 l O2 = 5 kcal = 20.9 kJ. However, an O2 deficit plus
      exercise O2 uptake measurement ignores energy expenditure during recovery, and an
      exercise O2 uptake plus EPOC measurement misrepresents anaerobic energy
      expenditure. An alternative solution has not yet been proposed. Anaerobic
      glycolysis and mitochondrial respiration are construed here as a symbiotic union
      of metabolic pathways, each contributing independently to energy expenditure and
      heat production. Care must be taken when using O2 uptake alone to quantify energy
      expenditure because various high-intensity exercise models reveal that O2 uptake
      can lag behind estimated energy demands or exceed them. The independent
      bioenergetics behind anaerobic glycolysis and mitochondrial respiration can
      acknowledge these discrepancies. Anaerobic glycolysis is an additive component to
      an exercise O2 uptake measurement. Moreover, it is the assumptions behind steady
      state O2 uptake that do not permit proper interpretation of energy expenditure
      during EPOC; 1 l O2 not = 20.9 kJ. Using both the O2 deficit and a modified EPOC
      for interpretation, rather than one or the other, leads to a better method of
      quantifying energy expenditure for higher intensity exercise and recovery.

PMID- 9535581
TI  - Bilateral deficit in plantar flexion: relation to knee joint position, muscle
      activation, and reflex excitability.
AB  - Six male subjects made maximal isometric plantar flexions unilaterally (UL) and
      bilaterally (BL), with the knee joint angle positioned at 90 degrees and 0
      degrees (full extension) and the ankle joint kept at 90 degrees. Plantar flexion
      torque and electromyogram (EMG) of the lateral gastrocnemius (LG) and the soleus
      (Sol) muscles were recorded. There was a deficit in torque in BL compared to UL
      (P<0.05), and the deficit was greater when the knee was extended than when bent
      to 90 degrees (13.9% vs 6.6%). The integrated EMG (iEMG) of UL and BL did not
      differ when the knee was at 90 degrees. On the other hand, when the knee was
      extended iEMG of LG was smaller for BL than for UL, suggesting that the larger
      bilateral deficit when the knee was extended was due to a reduced activity of the
      LG motor units. In addition, the H-reflex recorded from Sol when the
      contralateral leg was performing a maximal unilateral plantarflexion was reduced.
      This would indicate that the force deficit was associated with a reduction of
      motoneuron excitability.

PMID- 9535580
TI  - Acute hormonal responses to heavy resistance exercise in younger and older men.
AB  - The purpose of this investigation was to examine the acute responses of several
      hormones [total and free testosterone (TT and FT, respectively),
      adrenocorticotropic hormone (ACTH), cortisol (C), growth hormone (GH), and
      insulin (INS)] to a single bout of heavy resistance exercise (HRE). Eight younger
      [30-year (30y) group] and nine older [62-year (62y) group] men matched for
      general physical characteristics and activity levels performed four sets of ten
      repetitions maximum (RM) squats with 90 s rest between sets. Blood samples were
      obtained from each subject via an indwelling cannula with a saline lock pre
      exercise, immediately post-exercise (IP), and 5, 15 and 30 min post-exercise.
      Levels of TT, FT, ACTH, C and lactate significantly increased after HRE for both
      groups. Pre-HRE pairwise differences between groups were noted only for FT, while
      post-HRE pairwise differences were found for TT, FT, GH, glucose and lactate.
      Area under the curve analysis showed that the 30y group had a significantly
      higher magnitude of increase over the entire recovery period (IP, 5, 15, and 30
      min post-exercise) for TT, FT, ACTH and GH. Few changes occurred in the INS
      response with the only change being that the 62y group demonstrated a decrease
      IP. Lactate remained elevated at 30 min post-HRE. This investigation demonstrates
      that age-related differences occur in the endocrine response to HRE, and the most
      striking changes appear evident in the FT response to HRE in physically active
      young and older men.

PMID- 9535582
TI  - The influence of cold stress and a 36- h fast on the physiological responses to
      prolonged intermittent walking in man.
AB  - In a previous study, rectal temperature (Tre) was found to be lower, and oxygen
      consumption (VO2) and the respiratory exchange ratio (R) were higher in a cold
      (+5 degrees C), wet and windy environment (COLD), compared with a thermoneutral
      environment during intermittent walking at approximately 30% of peak VO2 (Weller
      AS, Millard CE, Stroud MA et al. Am J Physiol 272:R226-R233, 1997). The aim of
      the present study was to establish whether these cold-induced responses are
      influenced by prior fasting, as impaired thermoregulation has been demonstrated
      in cold-exposed, resting men following a 48-h fast. To address this question,
      eight men attempted a 360-min intermittent (15 min rest, 45 min exercise) walking
      protocol under COLD conditions on two occasions. In one condition, the subjects
      started the exercise protocol approximately 120 min after a standard meal (FED/
      COLD), whereas in the other the subjects had fasted for 36 h (FASTED/COLD). The
      first two exercise periods were conducted at a higher intensity (HIGHER, 6 km x
      h[-1] and 10% incline), than the four subsequent exercise periods (LOW, 5 km x h[
      1] and 0% incline). There was no difference in the time endured in FED/ COLD and
      FASTED/COLD. In FASTED/COLD compared with FED/COLD, R was lower during HIGHER and
      LOW, and Tre was lower during LOW, whereas there was no difference in VO2, mean
      skin temperature and heart rate. Therefore, although the 36-h fast impaired
      temperature regulation during intermittent low-intensity exercise in the cold,
      wet and windy environment, it was unlikely to have been the principal factor
      limiting exercise performance under these experimental conditions.

PMID- 9535583
TI  - Effect of intense interval workouts on running economy using three recovery
      durations.
AB  - The purposes of this study were to determine whether running economy (RE) is
      adversely affected following intense interval bouts of 10 x 400-m running, and
      whether there is an interaction effect between RE and recovery duration during
      the workouts. Twelve highly trained male endurance athletes [maximal oxygen
      consumption; VO2max = 72.5 (4.3) ml x kg(-1) x min(-1) mean (SD)] performed three
      interval running workouts of 10 x 400 m with a minimum of 4 days between runs.
      Recovery duration between the repetitions was randomly assigned at 60, 120 or 180
      s. The velocity for each 400-m run was determined from a treadmill VO2max test.
      The average running velocity was 357.9 (9.0) m x min(-1). Following the workout,
      the rating of perceived exertion (RPE) increased significantly (P < 0.01) as
      recovery duration between the 400-m repetitions decreased (14.4, 16.1, and 17.7
      at 180s, 120s, and 60 s recovery, respectively). Prior to and following each
      workout, RE was measured at speeds of 200 and 268 m x min(-1). Changes in RE from
      pre- to post-workout, as well as heart rate (HR) and respiratory exchange ratio
      (R) were similar for the three recovery conditions. When averaged across
      conditions, oxygen consumption (VO2) increased significantly (P < 0.01) from pre-
      to post-test [from 38.5 to 40.5 ml x kg(-1) x min(-1) at 200 m x min(-1), and
      from 53.1 to 54.5 ml x kg(-1) x min(-1) at 268 m x min(-1), respectively]. HR
      increased (from 124 to 138, and from 151 to 157 beats x min(-1) respectively) and
      R decreased (from 0.90 to 0.78, and from 0.93 to 0.89, respectively) at 200 and
      268 m x min(-1), respectively (P < 0.01). This study showed that RE can be
      perturbed after a high-intensity interval workout and that the changes in VO2, HR
      and R were independent of the recovery duration between the repetitions.

PMID- 9535584
TI  - Relevance of individual characteristics for human heat stress response is
      dependent on exercise intensity and climate type.
AB  - Multiple heterogeneous groups of subjects (both sexes and a wide range of maximal
      oxygen uptake VO2max, body mass, body surface area (AD),% body fat, and AD/mass
      coefficient) exercised on a cycle ergometer at a relative (%VO2max, REL) or an
      absolute (60 W) exercise intensity in a cool (CO 21 degrees C, 50% relative
      humidity), warm humid (WH 35 degrees C, 80%) and a hot dry (HD 45 degrees C, 20%)
      environment. Rectal temperature (Tre) responses were analysed for the influence
      of the individual's characteristics, environment and exercise intensity.
      Exposures consisted of 30-min rest, followed by 60-min exercise. The Tre was
      negatively correlated with mass in all conditions. Body mass acted as a passive
      heat sink in all the conditions tested. While negatively correlated with VO2max
      and VO2max per kilogram body mass in most climates, Tre was positively correlated
      with VO2max and VO2max per kilogram body mass in the WH/REL condition. Thus, when
      evaporative heat loss was limited as in WH, the higher heat production of the
      fitter subjects in the REL trials determined Tre and not the greater efficiency
      for heat loss associated with high VO2max. Body fatness significantly affected
      Tre only in the CO condition, where, with low skin blood flows (measured as
      increases in forearm blood flow), the insulative effect of fat was pronounced. In
      the warmer environments, high skin blood flows offset the resistance offered by
      peripheral adipose tissue. Contrary to other studies, Tre was positively
      correlated with AD/mass coefficient for all conditions tested. For both exercise
      types used, being big (a high heat loss area and heat capacity) was apparently
      more beneficial from a heat strain standpoint than having a favourable AD/mass
      coefficient (high in small subjects). The total amount of variance in Tre
      responses which could be attributed to individual characteristics was dependent
      on the climate and the type of exercise. Though substantial for absolute exercise
      intensities (52%-58%) the variance explained in Tre differed markedly for
      relative intensities: 72% for the WH climate with its limited evaporative
      capacity, and only 10%-26% for the HD and CO climates. The results showed that
      individual characteristics play a significant role in determining the responses
      of body core temperature in all conditions tested, but their contribution was low
      for relative exercise intensities when evaporative heat loss was not restricted.
      This study demonstrated that effects of individual characteristics on human
      responses to heat stress cannot be interpreted without taking into consideration
      both the heat transfer properties of the environment and the metabolic heat
      production resulting from the exercise type and intensity chosen. Their impact
      varies substantially among conditions.

PMID- 9535585
TI  - Endocrine responses during exercise-heat stress: effects of prior isotonic and
      hypotonic intravenous rehydration.
AB  - Exercise following exercise-induced dehydration (EID) has been shown to elevate
      concentrations of plasma norepinephrine (NE) and hypothalamic-pituitary-adrenal
      axis hormones. However, it is not known how intravenous (i.v.) rehydration (Rh)
      with isotonic (ISO) or hypotonic (HYPO) saline affects these hormone
      concentrations. It was hypothesized that HYPO, versus ISO, would lead to lower
      plasma NE and cortisol concentrations ([CORT]) during subsequent exercise
      following EID due to a decrease in plasma sodium concentration [Na+]. Eight non
      heat acclimated men completed three experimental treatments (counterbalanced
      design) immediately following EID (33 degrees C) to -4% body mass loss. The Rh
      treatments were i.v. 0.9% NaCl (ISO, 25 ml x kg[-1]), i.v. 0.45% NaCl (HYPO, 25
      ml x kg[-1]), and no fluid (NF). After Rh and rest (2 h total), the subjects
      walked at 53-54 percent of maximal O2 uptake for 45 min at 36 degrees C. After
      Rh, the following observations were made before/during exercise: percentage
      change in plasma volume (PV) was lower in NF compared to ISO and HYPO but similar
      between ISO and HYPO; delta[Na+] was similar between ISO and NF and higher in ISO
      compared to HYPO; delta plasma NE was higher in NF compared to ISO and HYPO, but
      similar between ISO and HYPO; delta plasma [CORT] was higher in NF compared to
      ISO and HYPO and higher in ISO compared to HYPO; rectal temperature was higher in
      NF compared to ISO and HYPO. These data would suggest that sympathetic nervous
      activity and [CORT] during exercise, subsequent to EID and Rh, was affected by
      lower PV (probably through cardiopulmonary baroreflexes) as well as core
      temperature. Furthermore, [CORT] was affected by delta[Na+] after Rh through an
      unknown mechanism.

PMID- 9535586
TI  - Chronobiological effects on exercise performance and selected physiological
      responses.
AB  - Previous studies investigating the impact of circadian rhythms on physiological
      variables during exercise have yielded conflicting results. The purpose of the
      present investigation was to examine maximal aerobic exercise performance, as
      well as the physiological and psychophysiological responses to exercise, at four
      different intervals (0800 hours, 1200 hours, 1600 hours, and 2000 hours) within
      the segment of the 24-h day in which strenuous physical activity is typically
      performed. Ten physically fit, but untrained, male university students served as
      subjects. The results revealed that exercise performance was unaffected by
      chronobiological effects. Similarly, oxygen uptake, minute ventilation and heart
      rate showed no time of day influences under pre-, submaximal, and maximal
      exercise conditions. Ratings of perceived exertion were unaffected by time of day
      effects during submaximal and maximal exercise. In contrast, rectal temperature
      exhibited a significant chronobiological rhythm under all three conditions. Under
      pre- and submaximal exercise conditions, significant time of day effects were
      noted for respiratory exchange ratio, while a significant rhythmicity of blood
      pressure was evident during maximal exercise. However, none of these
      physiological variables exhibited significant differential responses (percent
      change from pre-exercise values) to the exercise stimulus at any of the four time
      points selected for study. Conversely, resting plasma lactate levels and lactate
      responses to maximal exercise were found to be significantly sensitive to
      chronobiological influences. Absolute post-exercise plasma norepinephrine values,
      and norepinephrine responses to exercise (percent change from pre-exercise
      values), also fluctuated significantly among the time points studied. In summary,
      these data suggest that aerobic exercise performance does not vary during the
      time frame within which exercise is normally conducted, despite the fact that
      some important physiological responses to exercise do fluctuate within that time
      period.

PMID- 9535587
TI  - The spring-mass model and the energy cost of treadmill running.
AB  - During running, the behaviour of the support leg was studied by modelling the
      runner using an oscillating system composed of a spring (the leg) and of a mass
      (the body mass). This model was applied to eight middle-distance runners running
      on a level treadmill at a velocity corresponding to 90% of their maximal aerobic
      velocity [mean 5.10 (SD 0.33) m x s(-1)]. Their energy cost of running (Cr). was
      determined from the measurement of O2 consumption. The work, the stiffness and
      the resonant frequency of both legs were computed from measurements performed
      with a kinematic arm. The Cr was significantly related to the stiffness (P <
      0.05, r=-0.80) and the absolute difference between the resonant frequency and the
      step frequency (P < 0.05, r=0.79) computed for the leg producing the highest
      positive work. Neither of these significant relationships were obtained when
      analysing data from the other leg probably because of the work asymmetry observed
      between legs. It was concluded that the spring-mass model is a good approach
      further to understand mechanisms underlying the interindividual differences in
      Cr.

PMID- 9535588
TI  - Beta-adrenergic blockade does not prevent polycythemia or decrease in plasma
      volume in men at 4300 m altitude.
AB  - When humans ascend to high altitude (ALT) their plasma volume (PV) and total
      blood volume (BV) decrease during the first few days. With continued residence
      over several weeks, the hypoxia-induced stimulation of erythropoietin increases
      red cell production which tends to restore BV. Because hypoxia also activates the
      beta-adrenergic system, which stimulates red blood cell production, we
      investigated the effect of adrenergic beta-receptor inhibition with propranolol
      on fluid volumes and the polycythemic response in 11 healthy unacclimatized men
      (21-33 years old exposed to an ALT of 4300 m (barometric pressure 460 Torr) for 3
      weeks on Pikes Peak, Colorado. PV was determined by the Evans blue dye method
      (PVEB), BV by the carbon monoxide method (BVCO), red cell volume (RCV) was
      calculated from hematocrit (Hct) and BVCO, and serum erythropoietin concentration
      ([EPO]) and reticulocyte count, were also determined. All determinations were
      made at sea level and after 9-11 (ALT-10) and 19-20 (ALT-20) days at ALT. At sea
      level and ALT, six men received propranolol (pro, 240 mg x day[-1]), and five
      received a placebo (pla). Effective beta-blockade did not modify the mean (SE)
      maximal values of [EPO] [pla: 24.9 (3.5) vs pro: 24.5 (1.5) mU x ml(-1)] or
      reticulocyte count [pla: 2.7 (0.7) vs pro: 2.2 (0.5)%]; nor changes in PVEB [pla:
      -15.8 (3.8) vs pro: -19.9 (2.8)%], RCVCO [pla: +7.0 (6.7) vs pro: + 10.1 (6.1)%],
      or BVCO [pla: -7.3 (2.3) vs pro: -7.1 (3.9)%]. In the absence of weight loss, a
      redistribution of body water with no net loss is implied. Hence, activation of
      the beta-adrenergic system did not appear to affect the hypovolemic or
      polycythemic responses that occurred during 3 weeks at 4300 m ALT in these
      subjects.

PMID- 9535589
TI  - Bias and limits of agreement between hydrodensitometry, bioelectrical impedance
      and skinfold calipers measures of percentage body fat.
AB  - Previous research has often used correlations as a statistical method to show
      agreement; however, this is not a valid use of the statistic. The purpose of this
      study was to investigate the bias and limits of agreement for three methods of
      estimating percentage body fat for 117 male and 114 female university athletes:
      hydrodensitometry (HYD), bioelectrical impedance (BIA) and skinfold calipers
      (SKF). The mean (SD) percentage body fat for males as assessed by HYD, BIA and
      SKF methods, respectively, were 13.2 (3.3)%, 14.1, (3.3)% and 13.0 (3.2)%. Female
      body fat measurements were 22.5 (3.9)%, 23.7 (4.3)% and 23.8 (4.2)%,
      respectively. Pearson product moment correlations for male and female body fat
      percentages between the three methods were high, ranging from 0.81 to 0.86 (P <
      0.05). However, compared to the criterion measure of body fat percentage (HYD),
      the magnitude of agreement BIA and SKF revealed a different pattern. The mean
      absolute difference between HYD and BIA measurements of body fat for males was 
      0.8 (2.0)% fat, and between HYD and SKF was it was 0.2 (1.7)% fat. The mean
      absolute difference for females between HYD and BIA was -1.2 (2.5)%; for HYD and
      SKF it was -1.4 (2.2)%. Compared to the HYD measures for males and females, the
      BIA and SKF measures were as much as a 3.8% underestimation and a 6.2%
      overestimation of body fat. This study provides evidence that the strength of a
      correlation does not indicate agreement between two methods. In future,
      reliability and validity studies should examine the absolute differences between
      two variables and calculate limits of agreement around which a practitioner can
      appreciate the precision of the methodologies.

PMID- 9535590
TI  - Cardiorespiratory responses to underwater treadmill walking in healthy females.
AB  - This study compared the cardiorespiratory responses of eight healthy women (mean
      age 30.25 years) to submaximal exercise on land (LTm) and water treadmills (WTm)
      in chest-deep water (Aquaciser). In addition, the effects of two different water
      temperatures were examined (28 and 36 degrees C). Each exercise test consisted of
      three consecutive 5-min bouts at 3.5, 4.5 and 5.5 km x h(-1). Oxygen consumption
      (VO2) and heart rate (HR), measured using open-circuit spirometry and telemetry,
      respectively, increased linearly with increasing speed both in water and on land.
      At 3.5 km x h(-1) VO2 was similar across procedures [chi = 0.6 (0.05) l x min(
      1)]. At 4.5 and 5.5 km x h(-1) VO2 was significantly higher in water than on
      land, but there was no temperature effect (WTm: 0.9 and 1.4, respectively; LTm:
      0.8 and 0.9 l x min(-1), respectively). HR was significantly higher in WTm at 36
      degrees C compared to WTm at 28 degrees C at all speeds, and compared to LTm at
      4.5 and 5.5 km x h(-1) (P < or = 0.003). The HR-VO2 relationship showed that at a
      VO2 of 0.9 l x min(-1) x HR was higher in water at 36 degrees C (115 beats x min[
      1]) than either on land (100 beats min[-1]) or in water at 28 degrees C (99 beats
      x min[-1]). The Borg scale of perceived exertion showed that walking in water at
      4.5 and 5.5 km x h(-1) was significantly harder than on land (WTm: 11.4 and 14,
      respectively; LTm: 9.9 and 11, respectively; P < or = 0.001). These
      cardiorespiratory changes occurred despite a slower cadence in water (the mean
      difference at all speeds was 27 steps/min). Thus, walking in chest-deep water
      yields higher energy costs than walking at similar speeds on land. This data has
      implications for therapists working in hydrotherapy pools.

PMID- 9535591
TI  - Hypothalamic-pituitary-adrenal and -gonadal axis function after exercise in
      sedentary and endurance trained elderly males.
AB  - The aim of this study was to investigate hypothalamic-pituitary-adrenal (HPAA)
      and -gonadal (HPGA) axis responses to post-exercise (30 min at 65% VO2max)
      combined corticotrophin, luteinizing hormone and thyrotrophin releasing hormone
      challenge (0.7 microg/ kg body mass) in elderly distance runners (DR; age: 68.9+/
      4.2 year) and sedentary individuals (SI; age: 69.1+/-2.6 year). Plasma cortisol,
      growth hormone, prolactin, luteinizing hormone, follicle stimulating hormone and
      total testosterone (T) concentrations pre- and post-exercise as well as in
      response to stimulation did not differ between DR and SI. Plasma
      adrenocorticotropic hormone returned to pre-exercise level in DR 60 min and in SI
      90 min post-stimulation. Free T was lower in DR at all time points. Our results
      do not support the notion of altered releasing hormone-stimulable HPAA and HPGA
      synthesis-secretion capacity in elderly males after endurance training.

PMID- 9535592
TI  - Achilles tendon loading during walking: application of a novel optic fiber
      technique.
AB  - An optic fiber (0.5 mm) was utilized for the study of Achilles tendon forces
      (ATF) in eight volunteers who walked over a 10 m force platform at three speeds
      [1.1+/-0.1 m x s(-1), 1.5+/-0.1 m x s(-1) and 1.8+/-0.2 m x s(-1)]. The presented
      ATF-time curves showed great intersubject variation in magnitudes of the sudden
      release of force after initial contact and in the peak ATF's (1430+/-500 N). This
      intersubject variation in the peak force decreased only by 4% when cross
      sectional area of the tendon was considered. Measured ground reaction forces and
      plantar pressures confirmed that the subjects walked quite normally during
      recordings. The peak ATF was found to be rather insensitive to speed in contrast
      to the rate of ATF development which increased 32% (p < 0.5) from slow to fast
      walking speed. It is concluded that the optic fiber technique can be applied to
      study loading of the musculo-tendinous complex during normal locomotion such as
      walking.

PMID- 9535594
TI  - Circumvention of multidrug resistance in genitourinary tumors.
AB  - Chemotherapy is the principal strategy to systemically challenge metastasized
      cancers of genitourinary origin. Unfortunately, the efficacy of chemotherapy is
      often hampered by multidrug resistance, the resistance to a variety of
      structurally and functionally distinct cytotoxic agents. Multidrug resistance can
      be either intrinsic or acquired, and can be caused by several mechanisms. The so
      called classical multidrug resistance, mediated by the MDR1 gene product P
      glycoprotein, has been held mainly responsible for inferring the multidrug
      resistance phenotype on urologic malignancies. However, several other multidrug
      resistance pathways have been identified. Multidrug resistance can be caused by
      the membrane-bound multidrug-resistance-associated protein, the detoxifying
      glutathione metabolism, the antiapoptotic protein BCL2, and changes in levels or
      activity of the topoisomerase enzymes. Strategies to overcome multidrug
      resistance of genitourinary tumors have arisen from the better understanding of
      the biologic and molecular mechanisms of multidrug resistance, and have been
      studied in experimental and clinical settings. However, attempts to modulate
      multidrug resistance in clinical renal cell, bladder, prostate, and testicular
      cancer have not been very rewarding so far, despite the optimism that had arisen
      from experimental data. Nevertheless, application of novel therapies to reverse
      multidrug resistance and to increase efficacy of chemotherapy for urologic
      cancers should be further pursued, within the setting of controlled clinical
      trials, to improve on current strategies.

PMID- 9535593
TI  - Effect of exercise-induced muscle damage on the blood lactate response to
      incremental exercise in humans.
AB  - Eccentric muscle actions are known to induce temporary muscle damage, delayed
      onset muscle soreness (DOMS) and muscle weakness that may persist for several
      days. The purpose of the present study was to determine whether DOMS-inducing
      exercise affects blood lactate responses to subsequent incremental dynamic
      exercise. Physiological and metabolic responses to a standardised incremental
      exercise task were measured two days after the performance of an eccentric
      exercise bout or in a control (no prior exercise) condition. Ten healthy
      recreationally active subjects (9 male, 1 female), aged 20 (SD 1) years performed
      repeated eccentric muscle actions during 40 min of bench stepping (knee high
      step; 15 steps x min[-1]). Two days after the eccentric exercise, while the
      subjects experienced DOMS, they cycled on a basket loaded cycle ergometer at a
      starting work rate of 150 W, with increments of 50 W every 2 min until fatigue.
      The order of the preceding treatments (eccentric exercise or control) was
      randomised and the treatments were carried out 2 weeks apart. Two days after the
      eccentric exercise, all subjects reported leg muscle soreness and exhibited
      elevated levels of plasma creatine kinase activity (P < 0.05). Endurance time and
      peak VO2 during cycling were unaffected by the prior eccentric exercise. Minute
      volume, respiratory exchange ratio and heart rate responses were similar but
      venous blood lactate concentration was higher (P < 0.05) during cycling after
      eccentric exercise compared with the control condition. Peak blood lactate
      concentration, observed at 2 min post-exercise was also higher [12.6 (SD 1.4) vs
      10.9 SD (1.3) mM; P < 0.01]. The higher blood lactate concentration during
      cycling exercise after prior eccentric exercise may be attributable to an
      increased rate of glycogenolysis possibly arising from an increased recruitment
      of Type II muscle fibres. It follows that determination of lactate thresholds for
      the purpose of fitness assessment in subjects experiencing DOMS is not
      appropriate.

PMID- 9535596
TI  - Construction and voiding functions of three types of orthotopic neobladders using
      colonic segments: the Kobe University experience.
AB  - BACKGROUND: At Kobe University Hospital we have created orthotopic neobladders
      since 1988 by using several colonic segments. Various types of neobladders were
      compared and a detailed description of these procedures and the voiding function
      outcome is presented. METHODS: Thirty-two men with invasive bladder carcinoma or
      recurrent carcinoma in situ underwent a radical cystectomy followed by orthotopic
      neobladder replacement using a right colonic, ileocolic or sigmoid colonic
      segment. The functional capacity, percentage of residual urine volume,
      configuration of the neobladder, and location in the pelvis were evaluated 1 year
      after surgery. Voiding function was evaluated using a questionnaire which
      included questions on diurnal and nocturnal continence, and by uroflowmetric
      analysis. RESULTS: Operative time, blood loss, and functional neobladder capacity
      did not differ for the 3 types of neobladders. The configuration of the right
      colonic and ileocolic neobladders resembled the shape of a rugby ball. The
      configuration of the sigmoid neobladder was oval. The right colonic and ileocolic
      neobladders tended to be located along the right side wall of the pelvis. The
      sigmoid neobladder was located in the center of the pelvis. Daytime and nocturnal
      continence was not affected by either the type of neobladder or its configuration
      or position. Neobladders located in the center of the pelvis exhibited a better
      maximum flow rate than those located along the right wall of the pelvis.
      CONCLUSION: The technical difficulty in constructing the 3 types of neobladders
      was approximately the same. For better voiding a neobladder should be located in
      the center of the pelvis.

PMID- 9535595
TI  - Adoptive immunotherapy of patients with metastatic renal cell cancer using
      lymphokine-activated killer cells, interleukin-2 and cyclophosphamide: long-term
      results.
AB  - BACKGROUND: Initial results of adoptive immunotherapy using lymphokine-activated
      killer (LAK) cells and interleukin-2 (IL-2) appeared to offer promise for
      treating renal cell cancer (RCC). However, lower response rates were seen in
      subsequent trials, and the long-term results of this treatment method have not
      been fully reported. In this study, we examine long-term results of adoptive
      immunotherapy using LAK cells, IL-2, and cyclophosphamide (LAK/IL-2/CPM therapy).
      METHODS: We administered 10 courses of therapy to 9 patients with advanced RCC.
      One patient had liver and para-aortic lymph node metastases; the others had only
      lung metastases. The clinical effects were initially evaluated 4 weeks after
      therapy and follow-up was continued for periods of 43 to 76 months. RESULTS: The
      4-week evaluation revealed 3 complete responses (CR), 3 partial responses (PR), 1
      minor response (MR), 1 patient with no change in disease status (NC), and 2
      patients whose disease progressed (PD). One CR patient remained apparently free
      of disease for 43 months. After tumors recurred in the lung of another CR patient
      further disease progression was suppressed by IL-2 administration until the
      patient died from other causes at 46 months. The third CR patient showed tumor
      recurrence in the lung and was re-treated with the same LAK/CPM/IL-2 therapy.
      Lung tumors decreased in size (PR), but the patient died due to brain metastasis
      2 months after the second round of treatment. The 2 initial PR patients, as well
      as the MR and NC patients, developed regrowth or new metastatic lesions within 2
      to 15 months following therapy. The 2 PD patients died 2 and 9 months after
      therapy. CONCLUSION: Long-term effects of LAK/IL-2/CPM therapy were not
      correlated with the maximal response observed 4 weeks after therapy. Although
      LAK/IL-2/CPM therapy appears suitable for use as induction therapy in RCC, our
      data suggest that long-term suppression will require surgical removal of remnant
      tumors or more intensive maintenance therapy.

PMID- 9535597
TI  - Clinical evaluation of random biopsy of urinary bladder in patients with
      superficial bladder cancer.
AB  - BACKGROUND: Superficial bladder cancer has a tendency to recur in the urinary
      bladder. One reason for recurrence is the presence of concomitant carcinoma in
      situ (CIS) or dysplasia. However, the usefulness of random biopsy of the urinary
      bladder has been unclear. METHODS: Between September 1990 and March 1996, 83
      patients with superficial bladder cancer underwent mucosal biopsy of 6 different
      sites in the urinary bladder with macroscopically normal findings (random
      biopsy). The relationship between a positive biopsy (CIS or dysplasia) and the
      tumor characteristics was examined. The disease-free survival of the patients
      according to the biopsy results was determined. RESULTS: The positive biopsy rate
      was 24.1% (CIS, 14.5%; dysplasia, 9.6%). The incidence of positive biopsy in
      patients with high-grade (G3), pT1 tumors, 3 or more and non-papillary wide-based
      tumors was significantly higher than that in patients with 1 or 2 tumors, low
      grade (G1, G2), pTa tumors and papillary tumors (P < 0.05). In patients with a
      single papillary tumor, positive biopsy was found in 9.5%. The disease-free
      survival in patients with a positive biopsy did not differ from that in patients
      with a negative biopsy, because intravesical bacillus Calmette-Guerin was
      instilled in patients with a positive biopsy. CONCLUSION: Our results indicate
      that random biopsy is useful for detecting concomitant CIS or dysplasia and in
      the choice of drugs for intravesical instillation.

PMID- 9535598
TI  - Vesicourethral dysfunction following radical surgery for rectal carcinoma: change
      in voiding pattern on sequential urodynamic studies and impact of nerve-sparing
      surgery.
AB  - OBJECTIVES: Urodynamic studies were performed to clarify vesicourethral
      dysfunction and recovery after rectal surgery for cancer. MATERIALS AND METHODS:
      At 1, and 6 to 1 2 months after rectal surgery interviews and urodynamic studies
      (UDS) were performed on 51 consecutive patients, all without a prior history of
      voiding disorder (40 males and 11 females; median age, 60 years). Patients were
      divided into 2 groups, either with (preserved group, n = 17) or without
      (nonpreserved group, n = 34) preservation of the bilateral pelvic plexus during
      surgery. Comparisons of voiding status and urodynamic parameters were made
      between the 2 groups. RESULTS: By 1 and 6 months after the operation normal
      voiding was achieved in 71% (12/17) and 100% (13/13) of patients in the preserved
      group, and 6% (2/34) and 30% of patients (9/30) in the nonpreserved group,
      respectively (P < 0.001). Attainment of normal voiding in the nonpreserved group
      was preceded by the recovery of bladder sensation, while UDS demonstrated
      increases in vesical compliance and the disappearance of vesical denervation
      supersensitivity. CONCLUSION: A nerve-sparing procedure during radical surgery
      for rectal carcinoma preserved vesicourethral function. The urodynamic parameters
      relevant to postoperative recovery of voiding function were improved vesical
      compliance, disappearance of vesical denervation supersensitivity, and recovery
      of a bladder filling sensation.

PMID- 9535599
TI  - Persistent vesicourethral dysfunction following radical surgery for rectal
      carcinoma: urodynamic features and potential abatement with modified
      sphincterotomy (radical transurethral resection of the prostate).
AB  - BACKGROUND: Vesicourethral function returns after radical rectal surgery during
      the first year but rarely progresses after 1 year. We examined the urodynamics of
      patients whose voiding dysfunction remained after 1 year, and treated several
      with a modified sphincterotomy procedure similar to radical transurethral
      resection of the prostate. METHODS: We analyzed the urodynamic features of
      vesicourethral dysfunction in 16 male patients with persistent voiding
      dysfunction for more than 1 year following radical surgery for rectal carcinoma.
      Seven patients elected to undergo radical transurethral resection of prostate
      (radical TUR-P) for the relief of their persistent voiding dysfunction. RESULTS:
      The mean bladder volume at the first desire to void was 210 mL, the mean maximal
      bladder capacity was 343 mL, and the mean vesical compliance (Cves) was 27.1
      mL/cm H2O. All patients demonstrated either vesical denervation supersensitivity
      (Vds) or uninhibited contraction. The mean maximal urethral closure pressure was
      43.9 cm H2O, and urethral denervation supersensitivity was found in 77.8% (7/9),
      and sphincter dyssynergia in 66.7% (6/9) of patients. After radical TUR-P, 5
      patients became free from the use of self-catheterization, 1 patient had a
      reduced residual urine rate, and 1 patient was unchanged, but no patient noted a
      change in urinary control. CONCLUSION: Urethral dysfunction after radical rectal
      surgery was caused by failure of the bladder to empty along with an underactive
      detrusor. Radical TUR-P was effective in restoring voiding function in a selected
      group of these patients.

PMID- 9535600
TI  - Hormone/antihormone withdrawal and dexamethasone for hormone-refractory prostate
      cancer.
AB  - BACKGROUND: Flutamide withdrawal has been reported to benefit patients with
      hormone-refractory prostate cancer. Several studies have also demonstrated that a
      combination of corticosteroids and testicular androgen ablation lowers serum
      androgen levels and improves clinical response. The purpose of this study was to
      examine the effect of withdrawal of oral hormonal agents and administration of
      dexamethasone in stage D3 prostate cancer patients. METHODS: Sixteen patients
      with hormone-refractory prostate cancer were enrolled in the study. All patients
      had osseous metastasis and elevated serum prostate-specific antigen. Nine had
      been treated with chlormadinone acetate, 4 with estramustine phosphate, and 3
      with flutamide as first-line hormonal therapy. All patients had also been treated
      either with bilateral orchiectomy (13 cases) or a luteinizing hormone-releasing
      hormone (LH-RH) agonist (3 cases). Seven patients whose disease progressed
      following hormone withdrawal were treated with oral dexamethasone (initially 1.5
      mg/day, then tapered to 0.5 mg/day). RESULTS: Eight patients demonstrated a
      decrease in prostate-specific antigen of greater than 50% following hormone
      withdrawal. The time to cancer progression for these 8 patients was 2 to 15
      months (mean, 4 months). Among the patients receiving dexamethasone, 4 showed a
      greater than 90% decrease in prostate-specific antigen after 3 months' treatment.
      The time to disease progression for these 4 patients was 3 to 11 months.
      CONCLUSION: In treating hormone-refractory advanced prostate cancer, the first
      pharmacologic manipulation should be withdrawal of the oral component of combined
      hormonal therapy. Patients whose disease progresses after hormone withdrawal
      should then be treated with glucocorticoids such as dexamethasone.

PMID- 9535601
TI  - Clinical evaluation of serum prostate-specific antigen-alpha1-antichymotrypsin
      complex values in diagnosis of prostate cancer: a cooperative study.
AB  - BACKGROUND: We studied the clinical significance of serum prostate-specific
      antigen bound to alpha1-antichymotrypsin (PSA-ACT) values determined with a newly
      developed enzyme immunoassay. METHODS: Serum PSA-ACT values were determined in a
      total of 652 sera. Clinical utility for the diagnosis of prostate cancer was
      compared to that of Tandem-R PSA and gamma-seminoprotein (gamma-Sm). The new
      enzyme immunoassay is based on the use of the Stanford reference as an
      international standard for PSA assays. RESULTS: Serum PSA-ACT values ranged from
      less than 0.10 to 1.4 ng/mL in healthy males (n = 100) while values in patients
      with benign prostatic hyperplasia (n = 155) averaged 3.4 +/- 3.8 ng/mL (mean +/-
      SD). In patients with prostate cancer, serum PSA-ACT values increased
      significantly with progression of the clinical stage and there were statistically
      significant differences between benign prostatic hyperplasia and each stage of
      prostate cancer except for stage A. Using BPH levels as controls (4.8 ng/mL for
      PSA-ACT, 7.2 ng/mL for PSA, 3.8 ng/mL for gamma-Sm, and 2.4 ng/mL for the
      complexed/free PSA ratio of PSA-ACT/gamma-Sm), specificity was 80%. The
      sensitivity of prostate cancer detection was 79% for PSA-ACT, 77% for PSA, 57%
      for gamma-Sm, and 46% for the ratio between PSA-ACT/gamma-Sm. CONCLUSION:
      Although the determination of serum PSA-ACT showed essentially the same utility
      as that of PSA for the diagnosis of prostate cancer, PSA-ACT may allow prediction
      of the clinical stage. The PSA-ACT assay may therefore replace PSA in the
      detection of prostate cancer.

PMID- 9535602
TI  - Transurethral electrovaporization of the prostate: preliminary clinical results
      with pressure-flow analysis.
AB  - BACKGROUND: We evaluated the safety and efficacy of transurethral
      electrovaporization of the prostate (TVP) as a new alternative treatment for
      patients with benign prostatic hyperplasia. METHODS: A total of 22 patients with
      symptomatic benign prostatic hyperplasia, including 4 with urinary retention,
      underwent TVP. If enough of a cavity was not created after 60 minutes of
      vaporization, transurethral resection of the prostate (TURP) was performed
      successively. International Prostate Symptom Score (I-PSS) with quality-of-life
      index, maximum flow rate, and postvoid residual volume were measured at baseline
      and at 2 weeks, 1, 3, and 6 months. A pressure-flow study was performed at
      baseline and at 3 or 6 months after surgery. RESULTS: TURP was required in 10 of
      22 patients. At 6 months, mean I-PSS decreased from 20.0 to 5.2, quality-of-life
      index decreased from 4.6 to 1.1, mean maximum flow rate increased from 6.9 to
      16.7 mL/s, and postvoid residual volume decreased from 152 to 32 mL. Detrusor
      pressure at maximum flow decreased from 108 to 39 cm H2O, with a significant
      relief of bladder outlet obstruction in 93% of the patients. Mean decrease in
      hematocrit was 4.4%, and in serum sodium, 4.8 mEq/L. None of the patients
      required transfusions or had TUR syndrome. A urethral stricture and a severe
      stress incontinence developed in 1 patient. CONCLUSION: TVP seems to be a safe
      and effective alternative to a standard TURP associated with fewer intraoperative
      complications. Although preliminary clinical results have been promising, further
      study is necessary to establish long-term efficacy and safety of this procedure.

PMID- 9535603
TI  - Predictability of conventional tests for the assessment of bladder outlet
      obstruction in benign prostatic hyperplasia.
AB  - BACKGROUND: The degree of bladder outlet obstruction (BOO) in benign prostatic
      hyperplasia (BPH) is most accurately quantified by pressure flow studies (PFS),
      although these studies are more invasive and complicated than conventional tests.
      We examined how precisely conventional tests predicted the PFS-assessed degree of
      BOO. METHODS: The study population consisted of 232 BPH patients who had
      undergone routine conventional tests and PFS. Correlation of the conventional
      test results with the degree of BOO assessed by PFS was examined by Spearman's
      correlation coefficients. Regression and subgroup analyses were performed to
      predict the degree of BOO using the conventional test results as the explanatory
      variables. RESULTS: The degree of BOO correlated with prostate volume, the degree
      of endoscopic obstruction, and to a lesser extent, with the maximum flow rate
      (Qmax) and age. The predictability of conventional tests alone, or in
      combination, for BOO, was approximately 60% to 70%, which is not acceptable for
      investigational use. However, almost all patients with a prostate volume larger
      than 30 mL, or with severe obstruction on urethroscopic findings, had an
      obstructed bladder outlet. CONCLUSION: PFS is mandatory when the precise
      evaluation of the degree of BOO is required, and patients are highly likely to
      have an outlet obstruction when they have a prostate larger than 30 mL, or
      severely obstructed posterior urethra on endoscopy.

PMID- 9535605
TI  - Chemotherapy of metastatic testicular germ cell tumors: relationship of
      histologic response to size reduction and changes in tumor markers.
AB  - BACKGROUND: Although testicular germ cell tumor is one of the most curable
      cancers, approximately 20% of advanced cases remain incurable. In this study we
      investigate factors that may predict a poor response to standard chemotherapeutic
      regimens and thus allow earlier initiation of more aggressive measures. METHODS:
      We analyzed the records of 19 patients with metastatic testicular germ cell
      tumors (8 seminomas and 11 nonseminomas). Sixteen patients underwent surgical
      exploration for residual tumors following chemotherapy, and the histological
      findings on the resulting specimens were correlated with reductions in tumor size
      observed on computed tomography and with changes in tumor marker levels. RESULTS:
      Complete necrosis was obtained in 10 of 12 lesions that shrank by at least 80%,
      while continued existence of teratoma or cancer was confirmed in 9 of 11 lesions
      with smaller size reductions. An initial human chorionic gonadotropin-beta
      subunit (HCG-beta) level more than 100 times the upper limit of normal appeared
      to predict poor histological response (teratoma/cancer) to chemotherapy. Slow
      fall (prolonged half-life) of tumor markers during chemotherapy also correlated
      with poor histological response. CONCLUSION: Factors which predict poor
      histological response of tumors to chemotherapy include size reduction less than
      80%, initial HCG-beta levels more than 100 times the upper limit of normal, and
      prolonged half-life of tumor markers (placental alkaline phosphatase, alpha
      fetoprotein and HCG-beta).

PMID- 9535604
TI  - Treatment for advanced testicular cancer with high-dose chemotherapy and
      autologous blood stem cell transplantation.
AB  - BACKGROUND: This study was carried out to investigate the efficacy and safety of
      high-dose chemotherapy (HDC) for the treatment of patients with advanced
      testicular cancer. METHODS: Seven patients were treated with high-dose
      carboplatin, etoposide, and ifosfamide followed by autologous blood stem cell
      transplantation. One patient received 1 cycle, 4 patients received 2 cycles, and
      2 patients received 3 cycles of HDC. We performed a total of 15 autologous blood
      stem cell transplantations: 8 with autologous bone marrow; 6 with peripheral
      blood stem cells; and 1 with peripheral blood stem cells in addition to
      autologous bone marrow. RESULTS: Four of the 7 patients achieved a pathologic
      complete response via early use of HDC and additional salvage surgery. All 4
      patients are still alive without evidence of disease at 12, 30, 33, and 54
      months, respectively. One patient is alive with active disease at 35 months. Two
      patients refractory to conventional chemotherapy died of progressive disease at 5
      and 27 months, respectively. The hematologic recovery after HDC was rapid, and
      peripheral blood stem cells tended to have shorter hematologic recovery compared
      with those from autologous bone marrow, although the difference was not
      significant. Nonhematologic toxicity was usually mild and manageable. CONCLUSION:
      High-dose chemotherapy, followed by autologous blood stem cell transplantation,
      may be safe and effective for patients with advanced testicular cancer,
      particularly when early use of HDC is conducted for chemotherapy-sensitive
      patients. A further large, long-term, follow-up study will be needed to define
      the role of HDC.

PMID- 9535606
TI  - Testicular findings, endocrine features and therapeutic responses of men with
      acquired hypogonadotropic hypogonadism.
AB  - BACKGROUND: Men with acquired hypogonadotropic hypogonadism (AHH) who desire
      restoration of fertility are treated with exogenous gonadotropin. However,
      gonadotropin (Gn) therapy does not always restore testicular function. It is
      unknown whether the therapeutic responses to Gn therapy correlate with their
      testicular histological findings. Thus, we analyzed factors influencing
      testicular dysfunction and therapeutic responses in AHH. METHODS: Of 21 men with
      AHH, 11 had no postmeiotic germ cells and were classified as the severe
      spermatogenic failure group. These were compared with the other 10 patients who
      had postmeiotic germ cells and comprised the mild spermatogenic failure group.
      RESULTS: Testicular volume and tubular diameter were significantly smaller, and
      the basement membrane and tunica propria were significantly thicker in the severe
      failure group. The gonadotropin basal level and response to exogenous
      gonadotropin-releasing hormone, and the testosterone response to exogenous human
      chorionic gonadotropin were significantly lower in the severe failure group of
      patients. Also, the recovery of spermatogenesis and testosterone secretory
      potentials was poor in the cases with a duration between diagnosis and treatment
      of 2 years or more. CONCLUSION: Longer periods without treatment may be
      responsible for irreversible testicular dysfunction in AHH. Gn therapy should be
      initiated very soon after the diagnosis of AHH if fertility is desired.

PMID- 9535607
TI  - Lack of selectin-dependent adhesion in prostate cancer cells expressing sialyl
      Le(x).
AB  - BACKGROUND: Recently, it has been reported that upregulation of the
      oligosaccharide sialyl Le(x) (SLe[x]) in prostate cancer is associated with
      hormone-resistant, aggressive disease. However, it is not clear that SLe(x)
      expressed on prostate cancer cells has a biological function related to
      metastatic potential. METHODS: The expression levels of SLe(x), sialyl Le(a)
      (SLe[a]), disialosyl galactosylgloboside (DSGG), monosialosyl galactosylgloboside
      (MSGG) and variousfucosyltransferases in 3 prostate cancer cell lines were
      determined. The function of SLe(x) expressed on prostate cancer cell lines was
      determined by a selectin-dependent adhesion assay. RESULTS: No prostate cancer
      cell lines expressed SLe(a), DSGG, or MSGG, but all prostate cancer cells
      moderately expressed SLe(x). Fucosyltransferase expression did not correlate with
      the expression of SLe(x), and all prostate cancer cells failed to bind
      immobilized selectin. CONCLUSION: The expression of SLe(x) on these prostate
      cancer cells does not correlate with selectin-dependent adhesion.

PMID- 9535608
TI  - Chromophobe cell renal carcinoma in childhood.
AB  - We report the first case of chromophobe cell renal carcinoma in childhood. A 12
      year-old boy presented gross hematuria following minor trauma. He was diagnosed
      as having a left renal tumor 45-mm in diameter. Radical nephrectomy was
      performed. One year later the boy was well.

PMID- 9535609
TI  - Renal vein thrombosis misdiagnosed as a renal cell carcinoma with a tumor
      thrombus in the inferior vena cava.
AB  - A 69-year-old man was diagnosed with a right renal carcinoma with a tumor
      thrombus in the inferior vena cava, and underwent a radical nephrectomy. The
      entire specimen was examined by step-wise sectioning and found to be a thrombus
      with extensive hemosiderin deposits and recanalization which contained no
      malignant cells.

PMID- 9535610
TI  - Cirsoid arteriovenous malformation of kidney presenting as a mass suggestive of
      malignancy.
AB  - This paper reports a rare case of cirsoid renal arteriovenous malformation (AVM)
      that showed radiological characteristics of a renal malignancy. Using only
      conventional procedures such as computerized tomography, the present case was
      misdiagnosed as a solid tumor mass and therefore radical nephrectomy was
      indicated. Angiographic analysis is expected to improve the accuracy of diagnosis
      of AVM, thus reducing the need to resort to invasive techniques.

PMID- 9535611
TI  - Azathioprine-induced megaloblastic anemia with pancytopenia 22 years after living
      related renal transplantation.
AB  - Macrocytosis and megaloblastic changes in the bone marrow are frequently seen in
      renal transplant recipients treated with azathioprine (Az). However, severe
      anemia is a rare side effect of Az. We recently observed a case of severe
      megaloblastic anemia with pancytopenia in a renal transplant recipient who had
      been receiving Az therapy for 22 years. The patient was a 46-year-old woman who
      had been administered Az and prednisolone at a dose of approximately 1.7 mg/kg
      and 0.17 mg/kg daily, respectively. A bone marrow aspiration revealed
      megaloblastic anemia with the depletion of myeloid cells and megakaryocytes. She
      did not have vitamin B12 or folate deficiency. Therefore, FK506 (tacrolimus), a
      macrolide produced by Streptomyces tsukubaensis, which acts directly on T cells
      and is known to have less myelosuppression than Az, was substituted for Az.
      Although the leukopenia improved, the anemia and thrombocytopenia did not improve
      in the short term. She developed dyspnea and severe subcutaneous bleeding of the
      right lower extremity due to knee contusions. Hemodialysis was started to treat
      her uremic state. Although it was impossible to evaluate the long-term effects of
      FK506 therapy for the pancytopenia in our case, the conversion from Az to a less
      myelosuppressive drug, such as FK506, should be considered in renal transplant
      recipients with severe myelosuppression caused by long-term Az treatment.

PMID- 9535612
TI  - Urodynamic changes after endoscopic correction of vesicoureteral reflux.
AB  - Massive bilateral vesicoureteral reflux (VUR) in a 7-year-old girl with spinal
      scoliosis was successfully treated by endoscopic correction. She was admitted due
      to a febrile urinary tract infection and urinary incontinence. A cystometrogram
      demonstrated normal detrusor function during storage. The endoscopic subureteric
      injection of polytetrafluoroethylene (Teflon) was performed, resulting in the
      disappearance of the VUR. A postoperative cystometrogram demonstrated overactive
      detrusor function during storage, necessitating anticholinergic medication. She
      has been free of febrile urinary tract infections and incontinence for 2 years
      postoperatively, although self-catheterization is necessary. In a case of
      neurogenic vesical dysfunction with massive reflux, endoscopic subureteric
      injection is not only a therapeutic tool, but also a useful diagnostic option for
      detecting occult detrusor overactivity during storage prior to open surgery.

PMID- 9535613
TI  - Testicular metastases from carcinoma of the bile duct: a case report.
AB  - A 41-year-old man was admitted to our hospital with chief complaints of painless
      tumor in the left scrotal contents and loss of body weight. As the tumor was
      suspected of being a neoplastic lesion, left radical inguinal orchiectomy was
      carried out. Histopathological examination showed metastatic adenocarcinoma of
      the bile duct. Metastatic carcinoma to the testicle, epididymis, and their tunics
      is unusual and testicular metastases from adenocarcinoma of the bile duct is
      extremely rare. A case of testicular metastases from carcinoma of the bile duct
      is reported and the literature reviewed.

PMID- 9535614
TI  - Left acute scrotum associated with appendicitis.
AB  - A 10-year-old boy, who had a mild inguinal hernia in his left scrotum, was
      referred to our clinic because of redness of the scrotal skin and tenderness of
      the left scrotal contents. Scrotal echography showed a hypoechoic lesion around
      the normal testis and epididymis. Because torsion of either the testis or
      testicular appendage was suspected, the scrotum was opened and 1.5 mL of purulent
      fluid was observed in the tunica vaginalis with inflammatory tissue around the
      testis and epididymis. On the first postoperative day, a low grade fever and
      abdominal tenderness persisted, however, the abdomen was flat and soft. There was
      no marked tenderness over McBurney's point, but there was moderate tenderness
      over Lanz's point on deep palpation. Abdominal sonography and magnetic resonance
      imaging revealed abscess formation between the bladder and the sacrum. With a
      diagnosis of perforation of the appendix, a laparotomy was performed. The
      inguinal hernia sac could not be observed on inspection, and it was not possible
      to palpate the left side because of severe adhesion due to infection. Also, the
      neck of the right inguinal sac could not be seen. The appendix specimen was
      gangrenous. On the second postsurgical day, all symptoms and signs disappeared.
      We present this rare condition and discuss the difficulty in establishing a
      diagnosis.

PMID- 9535615
TI  - The ocular melanoma story. LIII Edward Jackson Memorial Lecture: Part II.
AB  - PURPOSE: To trace the evolution and status of our knowledge of choroidal melanoma
      with regard to the nature, cause, and treatment of this tumor. METHODS:
      Historical materials beginning with Georg Bartisch's contributions in 1583
      through to the Collaborative Ocular Melanoma Study and recent basic research are
      reviewed. RESULTS: Many individuals have made important contributions to our
      knowledge about this tumor. Basic information, however, regarding the natural
      history of the tumor, the most effective treatment, and its cause is lacking.
      CONCLUSION: The Collaborative Ocular Melanoma Study will provide important
      information regarding the choice of treatment between enucleation and
      radiotherapy as well as natural history information, quality of life, and
      definitive pathology findings. Definitive treatment of choroidal melanoma will
      depend on knowledge of the genetic defects that cause the tumor. Within the next
      25 years, it is predicted that genetic defects will be determined and tumor
      samples will be obtained using small-needle aspiration and DNA probes located on
      microchips. In addition, treatment will then be based on drugs designed to
      inhibit molecules related to the genetic defect in the tumor.

PMID- 9535616
TI  - Vitreoretinal surgery for complications of congenital retinoschisis.
AB  - PURPOSE: To report the results of vitreoretinal surgery for the management of
      complications associated with congenital retinoschisis in children. METHODS: We
      conducted a review of consecutive children with complications of congenital
      retinoschisis treated with advanced vitreoretinal techniques. Nine eyes of seven
      patients with congenital retinoschisis had vitreoretinal surgery for one of the
      following complications of congenital retinoschisis: hemorrhage within a large
      schisis cavity with a dense vitreous hemorrhage; rapid progression of schisis
      threatening the macula; obscuration of the macula by the overhanging inner wall
      of a schisis cavity; a combined schisistraction retinal detachment; or a combined
      schisis-rhegmatogenous retinal detachment. Vitreoretinal surgery consisted of
      vitrectomy, inner schisis wall retinectomy, fluid-gas exchange, endolaser
      treatment, and perfluoropropane gas injection. After vitreoretinal surgery,
      patients were followed up for a mean of 26 months (range, 9 to 67 months).
      Retinal reattachment, visual acuity, and visual fields were used as outcome
      measures. RESULTS: Eight of nine eyes had successful retinal reattachment. Six
      eyes postoperatively had improved visual acuity or visual field, or both. One eye
      had stabilization of visual acuity, and two eyes had a decrease in visual acuity.
      CONCLUSION: In children with complications of congenital retinoschisis,
      vitreoretinal surgery with excision of the inner wall of the peripheral schisis
      cavity may be effective in achieving retinal reattachment, thereby improving
      visual acuity or visual field size.

PMID- 9535617
TI  - Influence of panretinal photocoagulation on the ocular pulse curve.
AB  - PURPOSE: To study the ocular pulsation amplitude (an indicator of choroidal
      circulation) and systolic ophthalmic artery pressure after panretinal
      photocoagulation. METHODS: Prospectively, in 10 patients with diabetes mellitus
      (eight with type II and two with type I; mean age, 64 years) and severe, hitherto
      untreated, bilateral proliferative diabetic retinopathy, we performed intensive,
      unilateral panretinal photocoagulation with 1,500 argon laser burns (spot size,
      500 microm) in two sessions (interval, 3 weeks). Before and (in 3-week intervals)
      up to 9 weeks after treatment, we recorded ocular pulse curves using oculo
      oscillodynamography and determined each patient's ocular pulsation amplitude and
      systolic ophthalmic artery pressure. RESULTS: Compared with the untreated contra
      lateral eyes, panretinal photocoagulation led to a reduction of ocular pulsation
      amplitude. Three weeks after the first coagulation, the reduction averaged 20%.
      Maximum reduction was found 9 weeks after onset of treatment (6 weeks after the
      second coagulation) and amounted to 29.9%. The differences between
      photocoagulated and untreated eyes were highly significant on average (P < .01;
      analysis of variance) as well as for time course (P < .001). Systolic ophthalmic
      artery pressure was not changed significantly during panretinal photocoagulation
      follow-up. CONCLUSIONS: Ocular pulsation amplitude is determined by the cardiac
      cycle-related intraocular volume changes that depend predominantly on choroidal
      blood flow. The morphologic substrate is probably choriocapillary closure after
      photocoagulation.

PMID- 9535618
TI  - Effect of chronic nitrate treatment on retinal vessel caliber in open-angle
      glaucoma.
AB  - PURPOSE: A recent report has suggested that nitrate therapy may delay the
      progression of glaucomatous damage. To investigate the mechanism that may mediate
      this effect, we sought to determine whether nitrate therapy is associated with
      retinal vasodilatation in patients with glaucoma. METHODS: Retinal venous and
      arterial diameters were determined from color fundus photographs of the optic
      nerve head obtained during a retrospective study designed to investigate any
      potential effects of chronic nitrate treatment on the progression of glaucomatous
      pathology. Fourteen eyes of 14 patients who were receiving chronic nitrate
      therapy for systemic diseases unrelated to glaucoma were randomly selected.
      Vascular measurements were compared with those of 15 eyes of 15 control patients
      with glaucoma who did not receive any nitrate therapy. RESULTS: In comparison
      with control patients, nitrate-treated patients showed significant average
      vasodilatation of 17% (P = .008) and 13% (P = .01) in the superior and inferior
      temporal retinal veins, respectively. A 5% increase in average retinal arterial
      diameter was also detected, but this was not statistically significant.
      CONCLUSION: Chronic nitrate treatment is associated with retinal venous
      dilatation in patients with glaucoma. Although not assessed in this study, it is
      possible that a protective effect of nitrates may be mediated by a vasoactive
      effect leading to improved perfusion of the retina and perhaps the optic nerve
      head, in a similar fashion to what has been observed in the circulation of the
      heart. Additional studies of the effect of nitrates on the ocular circulation are
      needed, however, to support this speculation.

PMID- 9535619
TI  - Dorzolamide hydrochloride and visual function in normal eyes.
AB  - PURPOSE: To determine by a pilot study whether standard treatment with the
      topical carbonic anhydrase inhibitor dorzolamide hydrochloride influences visual
      function under normal breathing conditions, during carbon dioxide inhalation, or
      during hyperventilation, and to establish criteria for future larger-scale
      studies. METHODS: We enrolled 12 normal subjects into this randomized double
      masked placebo-controlled crossover study. Each subject was treated with either
      dorzolamide 2% or placebo, three times daily, for 4 days. After a 2-week washout
      period, the alternative topical agent was used under identical testing
      conditions. On day 2 of each treatment phase, contrast sensitivities to
      sinusoidal gratings of 1 and 4 cycles per degree (cpd) were assessed. On day 4,
      mean deviation values from full-threshold 10-2 visual fields were obtained. Three
      sets of each visual function test were obtained before each treatment phase, and
      in sequence on each testing day, during normal breathing (baseline), inhalation
      of carbon dioxide-enriched air, and hyperventilation while intraocular pressure
      was monitored. RESULTS: Contrast sensitivity at 4 cpd decreased significantly (P
      < .01) during carbon dioxide supplementation with placebo but showed no
      significant change with dorzolamide. The decrease in contrast sensitivity
      accompanying hyperventilation was attenuated (by nearly 50% at 1 cpd) during
      dorzolamide treatment. Dorzolamide treatment was associated with higher perimetry
      mean deviation values under each treatment condition and was statistically
      significant (P < .05) at baseline. CONCLUSIONS: Dorzolamide appears to enhance
      contrast sensitivity in normal subjects during physiologic hypercapnia and
      hypocapnia at 4 and 1 cpd, respectively. Also, under normal breathing conditions,
      dorzolamide therapy increases perimetric light sensitivity.

PMID- 9535620
TI  - Distribution of central corneal thickness and its association with intraocular
      pressure: The Rotterdam Study.
AB  - PURPOSE: To perform a cross-sectional study on the distribution of central
      corneal thickness and its association with intraocular pressure in an elderly
      population. METHODS: We measured central corneal thickness and intraocular
      pressure in 395 subjects (352 control subjects, 13 patients with ocular
      hypertension, and 30 patients with primary open-angle glaucoma) aged 55 years or
      more. RESULTS: Mean central corneal thickness in the 352 control subjects was
      537.4 microm (95% confidence interval [CI], 533.8 to 540.9 microm; range, 427 to
      620 microm), with a maximal difference between eyes of 42 microm. There were no
      differences between sexes and no significant association with age. Linear
      regression analysis showed an increase of 0.19 mm Hg in intraocular pressure with
      each 10-microm increase in central corneal thickness (95% CI, 0.09 to 0.28 mm
      Hg). This association was similar in both eyes and in both sexes. The 13 patients
      with ocular hypertension had corneas a mean of 16.0 microm thicker (95% CI, -2.6
      to +34.6 microm) compared with control subjects (P = .093); the 30 patients with
      primary open-angle glaucoma had corneas a mean of 21.5 microm thinner (95% CI,
      8.8 to 34.1 microm) compared with control subjects (P = .001). CONCLUSION: Mean
      central corneal thickness was similar to that found in clinical studies, was
      slightly higher in patients with ocular hypertension, and was significantly lower
      in patients with primary open-angle glaucoma. Intraocular pressure was positively
      related with central corneal thickness. Central corneal thickness may influence
      the division between normal and increased intraocular pressure at a simple cutoff
      point of 21 mm Hg.

PMID- 9535621
TI  - Traumatic cataract in children: correction of aphakia by contact lens or
      intraocular lens.
AB  - PURPOSE: To compare the postoperative complications, visual outcome, and
      incidence of strabismus in children suffering from traumatic cataract corrected
      with contact lens or intraocular lens and to follow up the refractive changes in
      these eyes for an extended period of time. METHODS: Forty children, 2 to 13 years
      old at time of surgery for unilateral traumatic cataract, were followed up for
      1.5 to 11 years. Seventeen children were corrected with contact lenses and 23
      with intraocular lenses. Thirty-two underwent a primary posterior capsulectomy
      and anterior vitrectomy. RESULTS: The mean follow-up after surgery was 7.4 years
      for the children with contact lenses and 6.2 years for those with intraocular
      lenses. The incidence of secondary surgical interventions was higher among the
      children corrected with contact lenses. The eight children (five with contact
      lenses, three with intraocular lenses) who did not undergo primary posterior
      capsulectomy had Nd:YAG capsulectomy within 1 year after surgery. Fifteen of the
      23 children with intraocular lenses (65.2%) achieved a best-corrected visual
      acuity of 20/40, and 17 children (73.9%) had a final visual acuity of 20/50, but
      only five of 17 children with contact lenses (35.3%) achieved this level of
      visual acuity. CONCLUSIONS: Correction of unilateral aphakia by intraocular lens
      in children after traumatic cataracts results in better final visual acuities and
      binocularity with a smaller incidence of strabismus than when correction is
      carried out by contact lens. Intraocular lens implantation should be considered
      the primary aphakic correction in children with traumatic cataract.

PMID- 9535622
TI  - Sickle cell trait as a risk factor for secondary hemorrhage in children with
      traumatic hyphema.
AB  - PURPOSE: To determine risk factors for secondary hemorrhage and poor visual
      outcome in children with traumatic hyphemas. METHODS: We reviewed 99 eyes of 97
      children younger than 18 years who had been hospitalized for hyphema within 48
      hours of blunt eye trauma. Inpatient records were examined for race, age, sickle
      cell trait status, size of hyphema and intraocular pressure at admission,
      secondary hemorrhage (rebleed of hyphema), and medications while hospitalized.
      Fifty-five eyes of 53 children had at least 1 month of follow-up or attained best
      corrected visual acuity of 20/50 or better at their last outpatient visit.
      RESULTS: Among 99 eyes of 97 children with traumatic hyphema, secondary
      hemorrhage occurred in nine eyes (9%). Among 72 eyes of 70 African-American
      children, secondary hemorrhage occurred in nine eyes (14%), whereas in 27 eyes of
      27 white children, there were no secondary hemorrhages. However, when the 14 eyes
      of 13 sickle cell trait-positive children were excluded from the African-American
      group, the 57 eyes of sickle cell trait-negative African-American and white
      children did not have any secondary hemorrhages. The sickle cell trait-positive
      group had secondary hemorrhages in nine of 14 eyes (64%), significantly (P <
      .005) different from the 0% rate in the 57 eyes of African-American sickle cell
      trait-negative and white children. The sickle cell trait-positive group also had
      higher intraocular pressure and permanent visual impairment. CONCLUSION: Sickle
      cell trait is a significant risk factor for secondary hemorrhage, increased
      intraocular pressure, and permanent visual impairment in children who have
      traumatic hyphemas following blunt trauma.

PMID- 9535623
TI  - A controlled evaluation of the efficacy and safety of loteprednol etabonate in
      the prophylactic treatment of seasonal allergic conjunctivitis. Loteprednol
      Allergic Conjunctivitis Study Group.
AB  - PURPOSE: To evaluate the efficacy and safety of loteprednol etabonate 0.5% as
      prophylactic treatment for the ocular signs and symptoms of seasonal allergic
      conjunctivitis. METHODS: In this randomized, double-masked, placebo-controlled,
      parallel study, 293 adults with history of seasonal allergic conjunctivitis were
      treated with either loteprednol etabonate or vehicle (placebo) four times daily,
      beginning before the onset of the allergy season and continuing for 6 weeks. The
      primary efficacy measure was a primary composite score (sum of itching and bulbar
      conjunctival injection scores). Supportive efficacy measures were the
      investigator global assessment and a secondary composite score (sum of tearing,
      erythema, chemosis, and discomfort scores), all calculated during the 21-day peak
      pollen season. RESULTS: The proportion of patients who never developed moderate
      or severe signs and symptoms of allergy during the peak pollen season in the
      loteprednol etabonate treatment group was greater than that in the placebo group.
      For the primary composite score, this efficacy criterion was reached by 94% of
      patients (136/145) in the loteprednol etabonate group and 78% of patients
      (111/143) in the placebo group (P = .001). The magnitude of effect was similar
      for the investigator global assessment (86% [118/138] vs 64% [87/137]; P < .001)
      and, although not statistically significant, the secondary composite score (77%
      [112/145] vs 68% [97/143]; P = .092). None of the loteprednol etabonate-treated
      patients had an intraocular pressure increase of 10 mm Hg or more, whereas two
      placebo patients did. CONCLUSIONS: Loteprednol etabonate is generally effective
      in prophylaxis of seasonal allergic conjunctivitis and has an acceptable safety
      profile.

PMID- 9535624
TI  - Relative importance of quantifying area and vascular patterns in uveal melanomas.
AB  - PURPOSE: To test whether the cross-sectional area of choroidal and ciliary body
      melanomas and quantification of microcirculatory networks and parallel vessels
      with cross-linking are features associated with death from metastatic melanoma,
      and to compare new with conventional histologic prognostic features. METHODS: The
      cross-sectional area of 234 ciliary body or choroidal melanomas was measured from
      digitized images of histologic sections. The percentage of cross-sectional area
      occupied by two microcirculatory patterns-networks and parallel vessels with
      cross-linking-was calculated for the 152 tumors containing at least one focus of
      either pattern. Kaplan-Meier survival curves were generated based on cross
      sectional and percentage of cross-sectional areas of these patterns. Cox
      proportional hazard regression methods related time to death from melanoma with
      sets of predictor variables. For each model, percent variation explained was
      computed. RESULTS: Patient survival differs significantly when tumors are
      classified based on cross-sectional area: small (<16 mm2), medium (> or =16 mm2
      but <61.4 mm2), and large (> or =61.4 mm2). Patients with tumors containing
      networks and parallel vessels with cross-linking microcirculation patterns that
      occupy 2% of cross-sectional area have a significantly worse prognosis than do
      those patients with tumors containing a smaller percentage of these patterns.
      CONCLUSIONS: Quantifying cross-sectional tumor area and the percentage area
      occupied by networks and parallel vessels with cross-linking microcirculatory
      patterns in ciliary body and cho. roidal melanomas provides significant
      prognostic information. Compared with more conventional prognostic
      characteristics, the most dramatic increase in prognostic information is provided
      by determination of the presence or absence of microvascular patterns.

PMID- 9535625
TI  - Digital angiography of experimental choroidal melanomas using benzoporphyrin
      derivative.
AB  - PURPOSE: To examine benzoporphyrin derivative angiography as a modality for
      studying photosensitizer biodistribution in experimental choroidal melanomas.
      METHODS: A liposomal preparation of benzoporphyrin derivative was used in this
      study. Digital benzoporphyrin derivative angiograms were performed in 10 rabbits
      (six for experimental choroidal melanomas, two for normal choroids, and two for
      irides) using a Topcon ImageNet H1024 digital imaging system, a Kodak Megaplus
      video camera, and a Topcon TRC-50-VT fundus camera. Only one eye from each rabbit
      was used. Filters specifically designed for benzoporphyrin derivative (peak
      absorption at 580 nm and peak emission at 695 nm) were used. Benzoporphyrin
      derivative (1 mg/kg) was injected into an ear vein while images of tumor, normal
      choroid, or iris were being obtained. Follow-up images were obtained during the
      first 3 hours and at 24 hours after injection. Fluorescence microscopy was
      performed in all 10 rabbits using 1 mg/kg of benzoporphyrin derivative. Tumor
      bearing eyes were enucleated at the same time points that angiograms were
      performed, and the two sets of results were compared for maximum dye
      accumulation. RESULTS: Digital angiography demonstrated that maximal
      benzoporphyrin derivative fluorescence occurred in tumors 15 to 45 minutes after
      injection. Fluorescence photometry corroborated these results. CONCLUSION:
      Photosensitizer angiography is a valid modality for determining the optimum
      treatment time for photodynamic therapy.

PMID- 9535626
TI  - Glaucoma: a look beyond intraocular pressure.

PMID- 9535627
TI  - A system for classifying mechanical injuries of the eye (globe). The Ocular
      Trauma Classification Group.
AB  - PURPOSE: To develop a classification system for mechanical injuries of the eye.
      METHODS: The Ocular Trauma Classification Group, a committee of 13
      ophthalmologists from seven separate institutions, was organized to discuss the
      standardization of ocular trauma classification. To develop the classification
      system, the group reviewed trauma classification systems in ophthalmology and
      general medicine and, in detail, reports on the characteristics and outcomes of
      eye trauma, then established a classification system based on standard
      terminology and features of eye injuries at initial examination that have
      demonstrated prognostic significance. RESULTS: This system classifies both open
      globe and closed-globe injuries according to four separate variables: type of
      injury, based on the mechanism of injury; grade of injury, defined by visual
      acuity in the injured eye at initial examination; pupil, defined as the presence
      or absence of a relative afferent pupillary defect in the injured eye; and zone
      of injury, based on the anteroposterior extent of the injury. This system is
      designed to be used by ophthalmologists and nonophthalmologists who care for
      patients or conduct research on ocular injuries. An ocular injury is classified
      during the initial examination or at the time of the primary surgical
      intervention and does not require extraordinary testing. CONCLUSIONS: This
      classification system will categorize ocular injuries at the time of initial
      examination. It is designed to promote the use of standard terminology and
      assessment, with applications to clinical management and research stud ies
      regarding eye injuries.

PMID- 9535629
TI  - Retrobulbar anesthesia for repair of ruptured globes.
AB  - PURPOSE: To describe two cases involving patients with ruptured globes in whom
      retrobulbar anesthesia was used successfully. METHOD: A modified retrobulbar
      anesthesia technique was used to repair two ruptured globes in two patients in
      whom general anesthesia was contraindicated. RESULT: Using a modified technique,
      retrobulbar anesthesia did not cause wound gape or prolapse of intraocular
      contents. CONCLUSIONS: Most open globes should be repaired after administration
      of general anesthesia. Modified retrobulbar anesthesia can provide a reasonable
      alternative in rare situations in which general anesthesia subjects the patient
      to an unacceptable risk.

PMID- 9535628
TI  - Anterior lens capsule rupture caused by air bag trauma.
AB  - PURPOSE: To report a child with anterior lens capsule rupture caused by air bag
      inflation. METHODS: A 10-year-old girl sustained a rupture of the right anterior
      lens capsule secondary to air bag deployment during a minor automobile accident.
      The evaluation included orbital ultrasound and orbital computed tomography.
      RESULT: The right eye underwent lens aspiration with intraocular lens placement.
      Postoperatively, the patient did well with 20/25 best-corrected visual acuity.
      CONCLUSION: Our case, in which the patient's lens capsule was ruptured by air bag
      inflation, illustrates that air bag deployment, even in minor low-speed
      accidents, can cause severe blunt trauma to the eye.

PMID- 9535630
TI  - Intraorbital air simulating an intraocular foreign body.
AB  - PURPOSE: To present an ultrasonographic finding that simulated an intraocular
      foreign body after repair of a ruptured globe. METHOD: Case report. An
      ultrasonogram of a post-trauma eye was correlated with a computed tomographic
      scan. RESULTS: B-scan ultrasonography was performed on an eye after repair of a
      corneoscleral laceration. The ultrasonogram showed a highly reflective echo
      source suggestive of a foreign body; however, an orbital computed tomographic
      scan demonstrated that the lesion was intraorbital air. CONCLUSION: Although a
      highly reflective echo source in the presence of a ruptured globe may suggest a
      foreign body, the presence of orbital air should also be considered when
      interpreting ultrasonograms used in the preoperative and postoperative management
      of globe trauma.

PMID- 9535631
TI  - Spontaneous disappearance of traumatic macular holes in young patients.
AB  - PURPOSE: To report the disappearance of traumatic macular hole in three eyes of
      three patients. METHODS: Clinical data of the patients were reviewed. RESULTS:
      The three patients were relatively young, ranging in age from 12 to 18 years old.
      In one eye of each patient, a small traumatic macular hole was observed at the
      first visit. Visual acuities ranged from 20/100 to 20/40. The macular holes
      resolved spontaneously 3 to 4 months after the trauma, and final visual acuity
      improved to 20/20 in all patients. CONCLUSION: Small traumatic macular holes in
      young patients can resolve spontaneously, and this can be associated with good
      visual recovery.

PMID- 9535632
TI  - Hyperplastic persistent pupillary membrane.
AB  - PURPOSE: To report a child with extensive bilateral hyperplastic pupillary
      membranes and good visual acuity. METHOD: We examined a 9-year-old child with
      bilateral hyperplastic persistent pupillary membranes present since birth.
      RESULTS: The patient had a visual acuity of BE, 20/30, stereopsis of 50 seconds
      of arc, orthophoria, and normal extraocular movements. The remainder of the
      ophthalmic examination was normal. CONCLUSION: Patients with bilateral
      hyperplastic pupillary membranes may not require surgical intervention.

PMID- 9535633
TI  - Streptococcal toxic shock syndrome complicating preseptal cellulitis.
AB  - PURPOSE: Although substantial morbidity is uncommon in preseptal cellulitis, the
      incidence of severe infection resulting from group A streptococcal infection is
      increasing. METHODS: A 62-year-old man was initially examined for preseptal
      cellulitis sustained after minor trauma to his brow. The patient rapidly
      experienced shock and multisystem organ failure. Intensive medical therapy
      prevented circulatory collapse and death. RESULTS: A diagnosis of streptococcal
      toxic shock syndrome secondary to group A beta hemolytic streptococcal infection
      was made based on culture results and clinical course. CONCLUSIONS: The
      ophthalmologist plays an essential role in diagnosing this condition. Aggressive
      and timely treatment are essential to preventing death.

PMID- 9535634
TI  - Metipranolol-associated nongranulomatous anterior uveitis.
AB  - PURPOSE: To describe the findings in a patient with a nongranulomatous anterior
      uveitis, presumed to be induced by metipranolol. METHOD: A 69-year-old woman
      developed bilateral, nongranulomatous, anterior uveitis while undergoing
      treatment with metipranolol 0.3% for primary open-angle glaucoma. Four months
      after resolution of the initial episode, the patient was challenged with
      metipranolol 0.3% in the right eye. RESULT: On reinstituting metipranolol 0.3%,
      the patient once again developed a unilateral, nongranulomatous, anterior uveitis
      in the challenged eye. CONCLUSION: Metipranolol 0.3% eyedrops, used to treat
      primary open-angle glaucoma, appear to cause a nongranulomatous anterior uveitis.

PMID- 9535635
TI  - Spontaneous resolution of an endocapsular hematoma.
AB  - PURPOSE: To report a case of endocapsular hematoma that cleared spontaneously
      without intervention. METHODS: We examined and followed up a 68-year-old man who
      developed an endocapsular hematoma 2 1/2 years after a standard extracapsular
      cataract extraction with posterior chamber intraocular lens implantation.
      RESULTS: After several months without intervention, the endocapsular hematoma
      completely resolved. CONCLUSIONS: Observation may be a rational treatment option
      in some patients with endocapsular hematoma.

PMID- 9535636
TI  - Pigmentary retinopathy in long chain 3-hydroxyacyl-coenzyme A dehydrogenase
      deficiency.
AB  - PURPOSE: To define the ophthalmologic findings in long chain 3-hydroxyacyl
      coenzyme A dehydrogenase deficiency, an inborn error of mitochondrial beta
      oxidation. METHOD: Case report. RESULTS: A 5-year-old girl with long chain 3
      hydroxyacyl-CoA dehydrogenase deficiency had a bilateral acquired disturbance of
      the retinal pigment epithelium consisting of a central macular spot and regularly
      spaced peripheral spots. Central and peripheral vision and dark adaptation
      appeared to be mildly compromised. Electroretinography showed abnormalities of
      the cone system. CONCLUSIONS: An excess of long chain and very long chain fatty
      acid intermediates has been postulated as the cause of the retinopathy in long
      chain 3-hydroxyacyl-CoA dehydrogenase deficiency and the biochemically related
      peroxisomal disorders. Dietary management may slow or halt progression.
      Ophthalmoscopic detection of regularly spaced pigment spots could help identify
      long chain 3-hydroxyacyl-CoA dehydrogenase deficiency in future cases.

PMID- 9535637
TI  - Primary antiphospholipid antibody syndrome and retinal occlusive vasculopathy.
AB  - PURPOSE: To report a 31-year-old healthy patient with retinal venous occlusion in
      his left eye attributable to primary antiphospholipid antibody syndrome. METHODS:
      The patient was examined clinically. Multiple serologic and clinical
      investigations were performed to determine the causative disease. He was closely
      followed up for more than 3 years. RESULTS: The presence of lupus anticoagulant
      in our patient was indicated by a kaolin clotting time index of 27 (normal, <17)
      and confirmed by the demonstration of IgG antibodies against phospholipids. After
      long-term oral anticoagulant treatment for 2 years, lupus anticoagulant levels
      returned to normal, and therapy was stopped. No further thrombotic event occurred
      during follow-up. CONCLUSIONS: In retinal vascular occlusions of unexplained
      origin, antiphospholipid antibodies may play an important role in the
      pathogenesis. Detecting these antibodies in the serum of patients with retinal
      vascular occlusion helps determine the appropriate treatment with long-term oral
      anticoagulants.

PMID- 9535638
TI  - Alternating amaurosis fugax and temporal arteritis.
AB  - PURPOSE: To describe a patient with alternating amaurosis fugax and the
      importance of this condition in diagnosing temporal arteritis. METHODS: Case
      report of a 77-year-old man who had numerous episodes of transient alternating
      loss of vision for several days. RESULTS: Temporal artery biopsy showed
      vasculitis with a giant cell component. CONCLUSIONS: Alternating amaurosis fugax
      in an elderly patient suggests arteritis rather than atheromatous disease, and
      temporal artery biopsy should be considered.

PMID- 9535639
TI  - Visual field loss resulting from cervical chiropractic manipulation.
AB  - PURPOSE: To report a complication of chiropractic cervical manipulation. METHOD:
      Case report. A healthy 39-year-old woman developed sudden left peripheral visual
      field loss after chiropractic neck manipulation. RESULTS: Visual field testing
      disclosed a left superior homonymous hemianopsia. A magnetic resonance imaging
      scan performed the day of the event disclosed acute infarction of the
      ventromedial aspect of the inferior right occipital lobe. CONCLUSION: Cerebral
      infarct may occur as a result of chiropractic neck manipulation.

PMID- 9535640
TI  - Ptosis secondary to amyloidosis of the tarsal conjunctiva and tarsus.
AB  - PURPOSE: To report a case of chronic unilateral ptosis in a 63-year-old,
      otherwise healthy woman with visual restriction. METHODS: We performed a biopsy
      on an enlarged tarsal plate that we believed had caused ptosis. A levator
      aponeurotic advancement was performed subsequently. RESULTS: Histologic and
      ultrastructural examination of the biopsy specimen disclosed amyloidosis of the
      tarsal conjunctiva and tarsus. There was no evidence of systemic amyloidosis.
      CONCLUSION: Localized amyloidosis involving the tarsal conjunctiva and tarsus is
      a rare cause of chronic eyelid thickening and ptosis.

PMID- 9535641
TI  - Orbital granulocytic sarcoma in an elderly patient.
AB  - PURPOSE: To report a 71-year-old woman with acute myelogenous leukemia in
      remission who developed orbital granulocytic sarcoma. METHODS: The patient was
      referred for acute proptosis and decreased vision of the right eye. Computed
      tomography of the orbits demonstrated a right extraconal mass compressing the
      optic nerve. A right lateral orbitotomy was performed, and a portion of the mass
      was excised for diagnostic purposes and orbital decompression. RESULTS:
      Histopathologic and immunohistochemical evaluation disclosed orbital granulocytic
      sarcoma. With chemotherapy and radiation, vision remained stable and right
      proptosis resolved. CONCLUSIONS: Orbital granulocytic sarcoma is usually
      diagnosed in children with a history of acute myelogenous leukemia. This case
      demonstrated that this entity may also occur rarely in older patients with a
      history of acute myelogenous leukemia.

PMID- 9535642
TI  - Burkitt lymphoma manifesting as acute proptosis.
AB  - PURPOSE: To describe an unusual case of Burkitt lymphoma manifesting as acute
      proptosis and simulating orbital inflammatory disease. METHODS: Case report.
      RESULTS: A 24-year-old Chinese man developed painful severe nonaxial proptosis in
      his left eye during 1 day. Computed tomographic scan disclosed an orbital mass
      that was shown to be Burkitt lymphoma when biopsy was performed. The disease
      progressed rapidly despite chemotherapy. CONCLUSIONS: Our case supports the fact
      that Burkitt lymphoma can manifest as acute proptosis and expands the spectrum of
      clinical presentation of Burkitt lymphoma.

PMID- 9535643
TI  - Scanning laser Doppler flowmeter study of retinal and optic disk blood flow in
      glaucomatous patients.

PMID- 9535644
TI  - Surgical vs medical management of chronic open-angle glaucoma.

PMID- 9535646
TI  - Natural and engineered disorders of lymphocyte development.
AB  - Mammals have evolved complex developmental pathways to generate a large
      repertoire of B and T lymphocytes capable of mounting effective immune responses.
      Analysis of natural and engineered immunodeficiencies constitutes a powerful
      approach to delineating these pathways and identifying the molecular sensors that
      couple the survival of developing lymphocytes to the achievement of successful
      gene rearrangements at the loci coding for B and T cell antigen receptors.
      Besides identifying cytokines, growth factors, and transcription factors involved
      in lymphocyte development, genetic analysis also makes it possible to organize
      most of these protagonists into gene networks that control critical events in the
      life of developing lymphocytes.

PMID- 9535647
TI  - Homeostasis and self-tolerance in the immune system: turning lymphocytes off.
AB  - The immune system responds in a regulated fashion to microbes and eliminates
      them, but it does not respond to self-antigens. Several regulatory mechanisms
      function to terminate responses to foreign antigens, returning the immune system
      to a basal state after the antigen has been cleared, and to maintain
      unresponsiveness, or tolerance, to self-antigens. Here, recent advances in
      understanding of the molecular bases and physiologic roles of the mechanisms of
      immune homeostasis are examined.

PMID- 9535648
TI  - Viral strategies of immune evasion.
AB  - The vertebrate body is an ideal breeding ground for viruses and provides the
      conditions that promote their growth, survival, and transmission. The immune
      system evolved and deals with this challenge. Mutually assured destruction is not
      a viable evolutionary strategy; thus, the study of host-virus interactions
      provides not only a glimpse of life at immunity's edge, but it has also
      illuminated essential functions of the immune system, in particular, the area of
      major histocompatibility complex-restricted antigen presentation.

PMID- 9535649
TI  - Temperature-induced momentum-dependent spectral weight transfer in
      Bi2Sr2CaCu2O8+delta 
AB  - Angle-resolved photoemission data from the cuprate superconductor
      Bi2Sr2CaCu2O8+delta above and below the superconducting transition temperature Tc
      reveal momentum-dependent changes that extend up to an energy of about 0.3
      electron volt, or 40kTc (where k is the Boltzmann constant). The data suggest an
      anomalous transfer of spectral weight from one momentum to another, involving a
      sizable momentum transfer Q approximately (0.45pi, 0). The observed Q is
      intriguingly near the charge-order periodicity required if fluctuating charge
      stripes are present.

PMID- 9535650
TI  - Optical studies of individual InAs quantum dots in GaAs: few-particle effects 
AB  - Optical emission from individual strained indium arsenide (InAs) islands buried
      in gallium arsenide (GaAs) was studied. At low excitation power density, the
      spectra from these quantum dots consist of a single line. At higher excitation
      power density, additional emission lines appeared at both higher and lower
      energies, separated from the main line by about 1 millielectron volt. At even
      higher excitation power density, this set of lines was replaced by a broad
      emission peaking below the original line. The splittings were an order of
      magnitude smaller than the lowest single-electron or single-hole excited state
      energies, indicating that the fine structure results from few-particle
      interactions in the dot. Calculations of few-particle effects give splittings of
      the observed magnitude.

PMID- 9535651
TI  - Delayed fracture of an inhomogeneous soft solid 
AB  - The spontaneous fracture of polymer gels was studied. Contrary to crystalline
      solids, where fracture usually happens instantaneously at a well-defined breaking
      strength, the fracture of a polymer gel can occur with a delay. When a constant
      force was applied, the cracks nucleated and started to propagate after a delay
      that can be as long as 15 minutes, depending on the force. This phenomenon can be
      understood by calculating the activation energy for crack nucleation in arbitrary
      dimension and accounting for the inhomogeneity of the gel network in terms of its
      fractal dimension.

PMID- 9535652
TI  - Thermographic selection of effective catalysts from an encoded polymer-bound
      library 
AB  - A general method is introduced for the rapid and simultaneous evaluation of each
      member of large encoded catalyst libraries for the ability to catalyze a reaction
      in solution. The procedure was used to select active catalysts from a library of
      potential polymer-bound multifunctional catalysts. From approximately 7000 beads
      screened (3150 distinct catalysts), 23 beads were selected for catalysis of an
      acylation reaction. Kinetic experiments indicate that the most strongly selected
      beads are also the most efficient catalysts.

PMID- 9535653
TI  - Polyolefin spheres from metallocenes supported on noninteracting polystyrene 
AB  - To obviate the destructive interaction of highly reactive metallocene catalysts
      with classical silica-based supports while retaining the advantage of supported
      catalysts, a noninteracting polystyrene support was developed. Supported
      catalysts for the polymerization of alpha-olefins are prepared by treating
      lightly cross-linked, chloromethylated polystyrene beads consecutively with a
      secondary amine, an ammonium salt of a weakly coordinating anion, and a neutral
      dialkylmetallocene. Catalytic sites are distributed homogeneously throughout the
      support particle, and the polymerization occurs within the bead, in contrast to
      traditional surface-supported metallocene catalysts. The copolymerization of
      ethylene and 1-hexene at 40 degreesC affords discrete spherical polyolefin beads
      with a size (0.3 to 1.4 millimeters) that varies according to the polymerization
      time.

PMID- 9535654
TI  - Friction anisotropy and asymmetry of a compliant monolayer induced by a small
      molecular tilt 
AB  - Lateral force microscopy in the wearless regime was used to study the friction
      behavior of a lipid monolayer on mica. In the monolayer, condensed domains with
      long-range orientational order of the lipid molecules were present. The domains
      revealed unexpectedly strong friction anisotropies and non-negligible friction
      asymmetries. The angular dependency of these effects correlated well with the
      tilt direction of the alkyl chains of the monolayer, as determined by electron
      diffraction and Brewster angle microscopy. The molecular tilt causing these
      frictional effects was less than 15 degrees, demonstrating that even small
      molecular tilts can make a major contribution to friction.

PMID- 9535655
TI  - Generation of intestinal T cells from progenitors residing in gut cryptopatches.
AB  - Cryptopatches (CPs) are part of the murine intestinal immune compartment. Cells
      isolated from CPs of the small intestine that were c-kit positive (c-kit+) but
      lineage markers negative (Lin-) gave rise to T cell receptor (TCR) alphabeta and
      TCR gammadelta intestinal intraepithelial T cells after in vivo transfer or
      tissue engraftment into severe combined immunodeficient mice. In contrast, cells
      from Peyer's patches and mesenteric lymph nodes, which belong in the same
      intestinal immune compartment but lack c-kit+Lin- cells, failed to do so. These
      findings and results of electron microscopic analysis provide evidence of a local
      intestinal T cell precursor that develops in the CPs.

PMID- 9535657
TI  - Conservation of substrate recognition mechanisms by tRNA splicing endonucleases.
AB  - Accuracy in transfer RNA (tRNA) splicing is essential for the formation of
      functional tRNAs, and hence for gene expression, in both Eukaryotes and Archaea.
      The specificity for recognition of the tRNA precursor (pre-tRNA) resides in the
      endonuclease, which removes the intron by making two independent endonucleolytic
      cleavages. Although the eukaryal and archaeal enzymes appear to use different
      features of pre-tRNAs to determine the sites of cleavage, analysis of hybrid pre
      tRNA substrates containing eukaryal and archaeal sequences, described here,
      reveals that the eukaryal enzyme retains the ability to use the archaeal
      recognition signals. This result indicates that there may be a common ancestral
      mechanism for recognition of pre-tRNA by proteins.

PMID- 9535656
TI  - Crystal structure and evolution of a transfer RNA splicing enzyme.
AB  - The splicing of transfer RNA precursors is similar in Eucarya and Archaea. In
      both kingdoms an endonuclease recognizes the splice sites and releases the
      intron, but the mechanism of splice site recognition is different in each
      kingdom. The crystal structure of the endonuclease from the archaeon
      Methanococcus jannaschii was determined to a resolution of 2.3 angstroms. The
      structure indicates that the cleavage reaction is similar to that of ribonuclease
      A and the arrangement of the active sites is conserved between the archaeal and
      eucaryal enzymes. These results suggest an evolutionary pathway for splice site
      recognition.

PMID- 9535658
TI  - Ribosome-catalyzed peptide-bond formation with an A-site substrate covalently
      linked to 23S ribosomal RNA.
AB  - In the ribosome, the aminoacyl-transfer RNA (tRNA) analog 4-thio-dT-p-C-p
      puromycin crosslinks photochemically with G2553 of 23S ribosomal RNA (rRNA). This
      covalently linked substrate reacts with a peptidyl-tRNA analog to form a peptide
      bond in a peptidyl transferase-catalyzed reaction. This result places the
      conserved 2555 loop of 23S rRNA at the peptidyl transferase A site and suggests
      that peptide bond formation can occur uncoupled from movement of the A-site tRNA.
      Crosslink formation depends on occupancy of the P site by a tRNA carrying an
      intact CCA acceptor end, indicating that peptidyl-tRNA, directly or indirectly,
      helps to create the peptidyl transferase A site.

PMID- 9535659
TI  - Visual input to the efferent control system of a fly's "gyroscope".
AB  - Dipterous insects (the true flies) have a sophisticated pair of equilibrium
      organs called halteres that evolved from hind wings. The halteres are sensitive
      to Coriolis forces that result from angular rotations of the body and mediate
      corrective reflexes during flight. Like the aerodynamically functional fore
      wings, the halteres beat during flight and are equipped with their own set of
      control muscles. It is shown that motoneurons innervating muscles of the haltere
      receive strong excitatory input from directionally sensitive visual interneurons.
      Visually guided flight maneuvers of flies may be mediated in part by efferent
      modulation of hard-wired equilibrium reflexes.

PMID- 9535660
TI  - A marine natural product inhibitor of kinesin motors.
AB  - Members of the kinesin superfamily of motor proteins are essential for mitotic
      and meiotic spindle organization, chromosome segregation, organelle and vesicle
      transport, and many other processes that require microtubule-based transport. A
      compound, adociasulfate-2, was isolated from a marine sponge, Haliclona (also
      known as Adocia) species, that inhibited kinesin activity by targeting its motor
      domain and mimicking the activity of the microtubule. Thus, the kinesin
      microtubule interaction site could be a useful target for small molecule
      modulators, and adociasulfate-2 should serve as an archetype for specific
      inhibitors of kinesin functions.

PMID- 9535661
TI  - The involvement of cell-to-cell signals in the development of a bacterial
      biofilm.
AB  - Bacteria in nature often exist as sessile communities called biofilms. These
      communities develop structures that are morphologically and physiologically
      differentiated from free-living bacteria. A cell-to-cell signal is involved in
      the development of Pseudomonas aeruginosa biofilms. A specific signaling mutant,
      a lasI mutant, forms flat, undifferentiated biofilms that unlike wild-type
      biofilms are sensitive to the biocide sodium dodecyl sulfate. Mutant biofilms
      appeared normal when grown in the presence of a synthetic signal molecule. The
      involvement of an intercellular signal molecule in the development of P.
      aeruginosa biofilms suggests possible targets to control biofilm growth on
      catheters, in cystic fibrosis, and in other environments where P. aeruginosa
      biofilms are a persistent problem.

PMID- 9535662
TI  - Coupling termination of transcription to messenger RNA maturation in yeast.
AB  - The direct association between messenger RNA (mRNA) 3'-end processing and the
      termination of transcription was established for the CYC1 gene of Saccharomyces
      cerevisiae. The mutation of factors involved in the initial cleavage of the
      primary transcript at the poly(A) site (RNA14, RNA15, and PCF11) disrupted
      transcription termination at the 3' end of the CYC1 gene. In contrast, the
      mutation of factors involved in the subsequent polyadenylation step (PAP1, FIP1,
      and YTH1) had little effect. Thus, cleavage factors link transcription
      termination of RNA polymerase II with pre-mRNA 3'-end processing.

PMID- 9535663
TI  - Rejoining of DNA by the RAG1 and RAG2 proteins.
AB  - Assembly of immunoglobulin and T cell receptor genes from separate gene segments
      [V(D)J recombination] begins with DNA double-strand breakage by the RAG1 and RAG2
      proteins, acting at a pair of recombination signal sequences (RSSs). Here, the
      RAG proteins are shown to reverse the cleavage reaction by joining an RSS to a
      broken coding sequence end. These "hybrid joints" have also been found in
      lymphoid cells, even when the normal pathway of DNA double-strand break repair is
      inactive, and can now be explained by this activity of the RAG proteins.

PMID- 9535664
TI  - Reduction of plasma homocyst(e)ine levels by breakfast cereal fortified with
      folic acid in patients with coronary heart disease.
AB  - BACKGROUND: The Food and Drug Administration (FDA) has recommended that cereal
      grain products be fortified with folic acid to prevent congenital neural-tube
      defects. Since folic acid supplementation reduces levels of plasma
      homocyst(e)ine, or plasma total homocysteine, which are frequently elevated in
      arterial occlusive disease, we hypothesized that folic acid fortification might
      reduce plasma homocyst(e)ine levels. METHODS: To test this hypothesis, we
      assessed the effects of breakfast cereals fortified with three levels of folic
      acid, and also containing the recommended dietary allowances of vitamins B6 and
      B12, in a randomized, double-blind, placebo-controlled, crossover trial in 75 men
      and women with coronary artery disease. RESULTS: Plasma folic acid increased and
      plasma homocyst(e)ine decreased proportionately with the folic acid content of
      the breakfast cereal. Cereal providing 127 microg of folic acid daily,
      approximating the increased daily intake that may result from the FDA's
      enrichment policy, increased plasma folic acid by 31 percent (P=0.045) but
      decreased plasma homocyst(e)ine by only 3.7 percent (P= 0.24). However, cereals
      providing 499 and 665 microg of folic acid daily increased plasma folic acid by
      64.8 percent (P<0.001) and 105.7 percent (P=0.001), respectively, and decreased
      plasma homocyst(e)ine by 11.0 percent (P<0.001) and 14.0 percent (P=0.001),
      respectively. CONCLUSIONS: Cereal fortified with folic acid has the potential to
      increase plasma folic acid levels and reduce plasma homocyst(e)ine levels.
      Further clinical trials are required to determine whether folic acid
      fortification may prevent vascular disease. Until then, our results suggest that
      folic acid fortification at levels higher than that recommended by the FDA may be
      warranted.

PMID- 9535665
TI  - Relation of alleles of the collagen type Ialpha1 gene to bone density and the
      risk of osteoporotic fractures in postmenopausal women.
AB  - BACKGROUND: Osteoporosis is a common disorder with a strong genetic component.
      One way in which the genetic component could be expressed is through polymorphism
      of COLIA1, the gene for collagen type Ialpha1, a bone-matrix protein. METHODS: We
      determined the COLIA1 genotypes SS, Ss, and ss in a population-based sample of
      1778 postmenopausal women using a polymerase-chain-reaction-based assay. We then
      related the genotypes to bone mineral density and the occurrence of osteoporotic
      fractures in these women. RESULTS: As compared with the 1194 women with the SS
      genotype, the 526 women with the Ss genotype had 2 percent lower bone mineral
      density at the femoral neck (P=0.003) and the lumbar spine (P=0.02); the 58 women
      with the ss genotype had reductions of 4 percent at the femoral neck (P= 0.05)
      and 6 percent at the lumbar spine (P=0.005). These differences increased with age
      (P=0.01 for modification by age of the effect of COLIA1 on femoral-neck bone
      density, and P=0.004 for modification of the effect on lumbar-spine bone
      density). Women with the Ss and ss genotypes were overrepresented among the 111
      women who had incident nonvertebral fractures (relative risk per copy of the s
      allele, 1.5; 95 percent confidence interval, 1.1 to 2.1). CONCLUSIONS: The COLIA1
      polymorphism is associated with reduced bone density and predisposes women to
      osteoporotic fractures.

PMID- 9535666
TI  - Clinical features associated with mutations in the chromosome 1 open-angle
      glaucoma gene (GLC1A)
AB  - BACKGROUND: A substantial proportion of cases of glaucoma have a genetic basis.
      Mutations causing glaucoma have been identified in the chromosome 1 open-angle
      glaucoma gene (GLC1A), which encodes a 57-kd protein known as myocilin. The
      normal role of this protein and the mechanism by which mutations cause glaucoma
      are not known. METHODS: We screened 716 patients with primary open-angle glaucoma
      and 596 control subjects for sequence changes in the GLC1A gene. RESULTS: We
      identified 16 sequence variations that met the criteria for a probable disease
      causing mutation because they altered the predicted amino acid sequence and they
      were found in one or more patients with glaucoma, in less than 1 percent of the
      control subjects. These 16 mutations were found in 33 patients (4.6 percent). Six
      of the mutations were found in more than 1 subject (total, 99). Clinical features
      associated with these six mutations included an age at diagnosis ranging from 8
      to 77 years and maximal recorded intraocular pressures ranging from 12 to 77 mm
      Hg. CONCLUSIONS: A variety of mutations in the GLC1A gene are associated with
      glaucoma. The spectrum of disease can range from juvenile glaucoma to typical
      late-onset primary open-angle glaucoma.

PMID- 9535667
TI  - Effect of the timing of treatment of port-wine stains with the flash-lamp-pumped
      pulsed-dye laser.
AB  - BACKGROUND: Port-wine stains can be treated with a flash-lamp-pumped pulsed-dye
      laser, but it is uncertain whether this treatment is more effective if
      administered early in life, when the skin is thinner and the lesion is smaller.
      METHODS: We prospectively studied 100 patients with a previously untreated port
      wine stain of the head or neck. They were treated with the flash-lamp-pumped
      pulsed-dye laser and divided into four age groups (0 to 5, 6 to 11, 12 to 17, and
      18 to 31 years). The outcome measure was lightening of the port-wine stain
      (reduction in the difference in color between the skin with the stain and
      contralateral healthy skin) as measured with a colorimeter after an average of
      five treatments (range, three to seven) of the entire lesion. RESULTS: Of the 100
      patients, 11 could not be included in the analysis because they had received
      fewer than three or more than seven treatments, had an erroneous base-line color
      measurement, or were lost to follow-up. The sizes, locations, and colors of the
      port-wine stains were similar among the groups. When all 89 patients were
      analyzed together, the average reduction in the difference in color between the
      skin with the port-wine stain and contralateral healthy skin was 40 percent. The
      differences between age groups in the average reduction in color differences were
      not significant (P= 0.26). By the end of the study, only 7 of 89 patients had
      completed laser therapy, and in no case was clearance complete. Treatment was
      discontinued in all seven because the last three treatments did not lead to
      further lightening. CONCLUSIONS: We found no evidence that treatment of port-wine
      stains with the flash-lamp-pumped pulsed-dye laser in early childhood is more
      effective than treatment at a later age.

PMID- 9535668
TI  - Images in clinical medicine. Thromboatheromatous aortic coarctation.

PMID- 9535669
TI  - Aging, health risks, and cumulative disability.
AB  - BACKGROUND: Persons with lower health risks tend to live longer than those with
      higher health risks, but there has been concern that greater longevity may bring
      with it greater disability. We performed a longitudinal study to determine
      whether persons with lower potentially modifiable health risks have more or less
      cumulative disability. METHODS: We studied 1741 university alumni who were
      surveyed first in 1962 (average age, 43 years) and then annually starting in
      1986. Strata of high, moderate, and low risk were defined on the basis of
      smoking, body-mass index, and exercise patterns. Cumulative disability was
      determined with a health-assessment questionnaire and scored on a scale of 0 to
      3. Cumulative disability from 1986 to 1994 (average age in 1994, 75 years) or
      death was the measure of lifetime disability. RESULTS: Persons with high health
      risks in 1962 or 1986 had twice the cumulative disability of those with low
      health risks (disability index, 1.02 vs. 0.49; P<0.001). The results were
      consistent among survivors, subjects who died, men, and women and for both the
      last year and the last two years of observation. The onset of disability was
      postponed by more than five years in the low-risk group as compared with the high
      risk group. The disability index for the low-risk subjects who died was half that
      for the high-risk subjects in the last one or two years of observation.
      CONCLUSIONS: Smoking, body-mass index, and exercise patterns in midlife and late
      adulthood are predictors of subsequent disability. Not only do persons with
      better health habits survive longer, but in such persons, disability is postponed
      and compressed into fewer years at the end of life.

PMID- 9535670
TI  - Homocysteine and atherothrombosis.

PMID- 9535672
TI  - Eat right and take a multivitamin.

PMID- 9535673
TI  - The genetic trail of osteoporosis.

PMID- 9535674
TI  - The search for glaucoma genes--implications for pathogenesis and disease
      detection.

PMID- 9535675
TI  - Aging better.

PMID- 9535676
TI  - Should we accept mediocrity?

PMID- 9535677
TI  - How large employers are shaping the health care marketplace. Second of two parts.

PMID- 9535678
TI  - The Millimeter-Wave Spectrum of DCCNC
AB  - The millimeter-wave spectrum of deuteroethynylisocyanide has been observed and
      analyzed in the ground and in the first excited vibrational states (v4, v5, v6,
      v7) = (0100), (0010), and (0001). Rotational, centrifugal distortion, and l-type
      doubling constants are given. Copyright 1998 Academic Press.

PMID- 9535679
TI  - The First Si-H Stretching Overtone of H3SiD: Emergence of Local Mode Effects
AB  - The FTIR spectrum of H3SiD in the 4100-4500-cm-1 region was recorded at Doppler
      limited resolution, and four bands were studied. At lower wavenumbers, two strong
      bands, which in the local mode picture can be assigned to (200, E) (nu0 =
      4308.5667 cm-1) and (200, A1) (nu0 = 4307.8441 cm-1), were analyzed, and at
      higher wavenumbers, two weaker bands, namely (110, E) at 4378.1950 cm-1 and (110,
      A1) at 4375.9763 cm-1, were analyzed. A total number of approximately 1900 lines
      in the strong dyad and 1000 lines in the weak one were assigned and fitted with
      standard deviations of the residuals approximately 0.0008 cm-1. The strong system
      (200) is close to local mode behavior, with no x, y Coriolis term needed and only
      a small z Coriolis term, and simple arithmetic relations between vibration
      rotation parameters are fulfilled as expected. The local mode behavior of the
      weak system (110) is less pronounced, but z and x, y Coriolis effects are smaller
      than in the Si-H stretching fundamentals. Comparison of computed and observed
      spectra provided a good estimate for the ratios of transition moments of the
      different bands: they are, in absolute value, proportional to 3.5:1.75:1:1 for
      (200, E), (200, A1), (110, E), and (110, A1), respectively. Copyright 1998
      Academic Press.

PMID- 9535680
TI  - The High-Resolution Vacuum Ultraviolet Emission Spectrum of Molecular Nitrogen
      from 82.6 to 124.2 nm: Level Energies of 10 Excited Singlet Electronic States
AB  - The high-resolution emission spectrum of molecular nitrogen was photographed in
      the vacuum ultraviolet from 82.6 to 124.2 nm. The use of a low-pressure Penning
      type electric discharge source has led to considerably reduced self-absorption at
      short wavelengths, making it possible to record as many as 283 emission bands.
      All emission bands have been rotationally analyzed, 215 being observed for the
      first time, and are reported in a separate publication. Energy values were
      deduced for the nonpredissociative or only slightly predissociative rovibronic
      levels in 10 singlet electronic excited states. Copyright 1998 Academic Press.

PMID- 9535681
TI  - On the Ground Electronic States of TiF and TiCl
AB  - The low-lying electronic states of TiF and TiCl have been studied using high
      level ab initio techniques. Both are found to have two low-lying excited
      electronic states, 4Sigma- (0.080 eV (TiF) and 0.236 eV (TiCl)) and 2Delta (0.266
      eV (TiF) and 0.348 eV (TiCl)), and 4Phi ground states at the highest CCSD(T)/6
      311++G(2d,2f) level of theory. Our theoretical predictions of 4Phi ground
      electronic states for TiF and TiCl support recent experimental findings by Ram
      and Bernath, and our calculated bond lengths and vibrational frequencies are in
      reasonable agreement with their experimental data. Copyright 1998 Academic Press.

PMID- 9535682
TI  - Carbon Dioxide Laser Saturation Spectroscopy and the Hyperfine Structure of
      Monosubstituted Ozone 16O16O17O and 16O17O16O
AB  - Carbon dioxide lasers have been used in an offset-lock configuration to obtain
      saturation spectra of ozone, monosubstituted with O-17, at a linewidth of a few
      kHz. Rich hyperfine structures result from the O-17 nucleus, spin 5/2. These are
      used, together with earlier microwave data, to obtain the corresponding hyperfine
      parameters. The spectra also illustrate the sensitivity of hyperfine structures
      to subtle vibration-rotation interactions. Copyright 1998 Academic Press.

PMID- 9535683
TI  - The Absorption Spectrum of H2S Between 2150 and 4260 cm-1: Analysis of the
      Positions and Intensities in the First (2nu2, nu1, and nu3) and Second (3nu2, nu1
      + nu2, and nu2 + nu3) Triad Regions
AB  - The two triad systems of hydrogen sulfide (2nu2, nu1, and nu3 near 4 um and 3nu2,
      nu1 + nu2, and nu2 + nu3 near 2.7 um) were analyzed using 14 spectra recorded at
      0.0056 and 0.011 cm-1 resolution with the McMath Fourier transform spectrometer
      located at Kitt Peak National Observatory. Experimental upper state levels of
      H232S, H234S, and H233S were obtained from assigned positions (as high as J = 20
      and Ka = 15 for the main isotope). These were fitted to the A-reduced Watson
      Hamiltonian to determine precise sets of rotational constants through J10 and up
      to nine Fermi and Coriolis coupling parameters. Intensities of the two H232S
      triads were modeled with rms values of 2.5%, using the transformed transition
      moment expansion with 19 terms for 568 intensities of the first triad and 11
      terms for the 526 intensities of the second triad. The second derivatives of the
      dipole moment with respect to normal coordinates were estimated in Debye to be:
      22ux = -0.004873 (90); 12ux = 0.01372 (30); and 23uz = 0.01578 (30). This
      confirmed that for hydrogen sulfide some of the second derivatives are larger
      than the first derivatives. The calculated line intensities were summed yielding
      integrated band strengths (in cm-2/atm at 296 K) as follows: 0.3315 for 2nu2,
      0.4522 for nu1, 0.1201 for nu3, 0.0303 for 3nu2, 1.820 for nu1 + nu2, and 2.869
      for nu2 + nu3. In addition, the hot band transitions were identified in both
      regions. Finally, a composite database of hydrogen sulfide line parameters was
      predicted for the 5- to 2.5-um region. Copyright 1998 Academic Press.

PMID- 9535684
TI  - Diode Laser Spectroscopy of the nu1 and nu3 Bands of SD+3
AB  - The nu1 and nu3 bands of SD+3 were observed at 5.45 um with a diode laser
      spectrometer. The ions were generated in a concentration-modulated, low
      temperature, hollow-cathode discharge of deuterium and carbonyl sulfide gases.
      One hundred and ninety-two lines were measured and assigned to SD+3. The majority
      of these lines were assigned to the nu3 perpendicular band with 49 lines assigned
      to the nu1 parallel band. A simultaneous fit of these bands provided the first
      experimental parameters for the SD+3 ion. Copyright 1998 Academic Press.

PMID- 9535685
TI  - Analytical Formulas for Long-Range Energies of the 16 Omega(+/-)g,u States of
      Alkali Dimers Dissociating into M(ns) + M(np 2PJ)
AB  - Analytical formulas for long-range energies of the 16 Omega(+/-)g,u states of
      alkali dimers dissociating into M(ns) + M(np 2PJ) are displayed in terms of the
      long-range Cn coefficients for the 2S+1Lambda(+)g,u corresponding states, and
      including exchange interaction energy contributions. Corrections due to
      retardation effects for resonant-dipole interactions are also included. For
      values of the internuclear distance R large enough so that only Coulombic
      interactions in R-3 are nonnegligible, the variation with R of the long-range
      energy is seen to be different from the usually assumed C3/R3 form. Present
      formulas can be used both to predict accurately long-range energies and to fit
      experimental energies now available in such long-range of R from photoassociative
      spectroscopy. As an example, they have been used, together with more accurate
      values of Cn coefficients than those used some 10 years ago, to predict again the
      three states of Rb2 displaying structures (well and barrier) at long range, i.e.,
      0(-)g(3/2), 1u(3/2), and 1u(1/2). Copyright 1998 Academic Press.

PMID- 9535686
TI  - Vibration-Internal Rotation-Overall Rotation Interactions in CH3OH
AB  - The zeroth order kinetic energy is developed for the vibrating-internally
      rotating-rotating CH3OH molecule using the general theory of Guan and Quade for
      large amplitude internal motion-vibration-rotation interactions in molecules. The
      R and T transformations are applied, respectively, to separate internal rotation
      from the other vibrations and overall rotation from the other vibrations in
      zeroth order. All zeroth order kinetic energy coefficients are calculated from
      the geometry and atomic masses of the CH3OH molecule. The physical significance
      of the two transformations is discussed in detail. This paper reports the results
      of the first segment of the many segments necessary in the calculations for full
      solution of the problem. Copyright 1998 Academic Press.

PMID- 9535687
TI  - Franck-Condon Factors and Analysis of Several Electronic Systems of C2
AB  - The D1Sigma+u-X1Sigma+g (Mulliken) and E1Sigma+g-A1Piu (Freymark) systems of C2
      have been analyzed. Molecular constants have been determined for the D1Sigma+u
      and E1Sigma+g states. Using these molecular constants, Franck-Condon factors
      (FCFs) have been calculated for the previously observed Mulliken and D1Sigma+u
      B'1Sigma+g band systems. FCFs for two new electronic transitions, D1Sigma+u-C1Pig
      and E1Sigma+g-D1Sigma+u, have also been calculated. Knowledge of FCFs will help
      spectroscopists in the search for and identification of these bands. Copyright
      1998 Academic Press.

PMID- 9535688
TI  - High-Resolution FTIR Study of Thiocarbonyl Difluoride SCF2
AB  - High-resolution ( approximately 3 x 10(-3) cm-1) FTIR spectra of the planar SCF2
      molecule have been recorded in the range of the four lowest-lying fundamentals
      nu2 (789.535 cm-1), nu3 (526.697 cm-1), nu5 (419.546 cm-1), and nu6 (623.187 cm
      1). For each band 4500-7500 transitions have been assigned and fitted to a
      standard Watson-type Hamiltonian up to quartic terms, sigma(Fit) approximately
      3.5 x 10(-4) cm-1. No indication of rovibrational perturbations was found,
      excited state rotational and centrifugal distortion constants being close to
      their ground state values. Ground state parameters previously determined from
      microwave spectra were, in part, improved by a merge of the appropriately
      weighted microwave data and approximately 10 000 ground state combination
      differences that were obtained from the nu4 band and spanning J and Ka values of
      88 and 49, respectively. Copyright 1998 Academic Press.

PMID- 9535689
TI  - Contribution of the Breakdown of the Born-Oppenheimer Approximation to Higher
      Order Dunham Coefficients
AB  - By means of a Deltaomega and DeltaB formalism for correction parameters,
      expressions were derived for higher-order Dunham coefficients, Y*vJ04, Y*vJ12,
      and Y*vJ21, in which contributions of the breakdown of the Born-Oppenheimer
      approximation were taken into account. Including Y*vJ04, Y*vJ12, and Y*vJ21, and
      Dunham's Y09, Y17, and Y25 coefficients in addition to the lower-order Y*vJij and
      Yk1 in the analysis, an extensive data set of the vibrational-rotational and the
      rotational transitions for four isotopomers of lithium hydride was fitted
      simultaneously to a single set of molecular constants within experimental errors.
      Since lithium hydride is a very light molecule, expressions shown in the present
      article should provide a means applicable to most cases of the spectral analysis
      of diatomic molecules in the 1Sigma state. Copyright 1998 Academic Press.

PMID- 9535691
TI  - Sub-Doppler Frequency Measurements of 15NH3 Laser Transitions
AB  - Copyright

PMID- 9535690
TI  - New Infrared Transitions in Solid Parahydrogen in the MIR and NIR/VIS Regions
AB  - We have studied the infrared spectrum of solid parahydrogen at different
      orthohydrogen impurity levels in the mid-infrared (MIR) region between 600-2000
      cm-1 and in the near infrared/visible (NIR/VIS) region between 10 000-16 500 cm
      1. The most important new observations in the MIR region, obtained with a single
      pass through an absorption cell 4.75 cm in length, are the U0(0) + S0(0) double
      transition around 1520 cm-1, broadened to about 20 cm-1 by roton delocalization,
      and the single orthohydrogen transition U0(1) at 1619.12 cm-1, which was
      previously observed only in normal hydrogen. For the NIR/VIS measurements an
      internal multireflection cell with 14-cm absorption path length was used. Of
      particular interest here is the second overtone band of solid hydrogen including
      double transitions of the type Q2(J) + Q1(J') (J = 0, 1; J' = 0, 1). At 10 241.07
      cm-1 the new single transition W2(0) could be observed. For several double
      transitions in the NIR/VIS region a fine structure is observed, which can be
      explained by anisotropic interaction in rotationally excited pairs of molecules.
      The treatment of the fine structure of the Q2(0) + S1(0) transition leads to the
      prediction of a considerable intensity of the triple transition Q2(0) + Q1(0) +
      S0(0). Stimulated by this result we have found the triple transitions Q1(0) +
      Q1(0) + S0(0) at 8660 cm-1 and S1(0) + Q1(0) + S0(0) at 8990 cm-1 in the first
      overtone region. At 12 788 cm-1 we detected an absorption feature that we have
      assigned to the triple transition S1(0) + Q1(0) + Q1(0). We explain the infrared
      activity of this transition in terms of a three-body process, a dipole moment
      induced within a triplet of hydrogen molecules by successive pairwise induction.
      Copyright 1998 Academic Press.

PMID- 9535692
TI  - High Resolution Spectrum of the (3-0) Band of the b1Sigma+g-X3Sigma-g Red
      Atmospheric System of Oxygen
AB  - Copyright

PMID- 9535693
TI  - Centrifugal Distortion Analysis of the Millimeter-Wave Spectrum of 1,1,1,2
      Tetrafluoroethane
AB  - Copyright

PMID- 9535696
TI  - Expression in Escherichia coli of the putative N-acetylneuraminate lyase gene
      (nanA) from Haemophilus influenzae: overproduction, purification, and
      crystallization.
AB  - The cloning and expression of the Haemophilus influenzae gene, nanA, for the
      putative N-acetylneuraminate lyase enzyme, also known as N-acetylneuraminic acid
      aldolase or sialic acid aldolase, are reported. The gene was isolated from ATCC
      type strain 49247 and cloned into the Escherichia coli expression vector pKKtac,
      which contained the strong tac promoter. Gene expression was compared with the
      homologous E. coli npl gene coding for the lyase. Purification protocols for the
      products of the nanA and npl genes are presented. Activity analysis showed that
      the nanA gene product is a sialic acid aldolase with more than threefold greater
      specific activity (6.9 IU/mg) than the enzyme from E. coli (</=2 IU/mg). A method
      for the provision of lyase orthorhombic crystals is reported. These crystals
      diffract to better than 2.0 A, which paves the way to the solution of the
      enzyme's three-dimensional structure.

PMID- 9535697
TI  - Renaturation of 1-aminocyclopropane-1-carboxylate synthase expressed in
      Escherichia coli in the form of inclusion bodies into a dimeric and catalytically
      active enzyme.
AB  - 1-Aminocyclopropane-1-carboxylate (ACC) synthase is a key enzyme regulating the
      biosynthesis of the plant hormone ethylene. A wound-inducible zucchini ACC
      synthase cDNA was isolated by reverse-transcription polymerase chain reaction (RT
      PCR) and expressed in a heterologous Escherichia coli BL21(DE3)pLysS:pET30a
      protein expression system. A method was developed and optimized for the
      renaturation of the ACC synthase expressed in the form of inclusion bodies. The
      optimum conditions were found to be unfolding in a buffer containing 100 mM Mops,
      pH 9.5, 6 M urea, and 50 mM DTT, for 3 h at 4 degrees C and refolding by a
      combined process of dialysis and dilution in 100 mM Mops, pH 8, 30 mM Chaps, and
      5 mM GSH at a protein concentration of 45 microg/ml. The purified enzyme has a
      specific activity of 90,000 U mg-1 and exhibits an apparent homogeneity on SDS
      PAGE fractionation. Biochemical characterization of the refolded enzyme revealed
      a high degree of similarity to the enzyme purified from the soluble source. The
      refolded enzyme was found to be a dimer with a native size of 110 kDa, a Km of 23
      microM, and a Vmax of 112,000 U mg-1.

PMID- 9535698
TI  - Secretion of recombinant pro- and mature fungal alpha-sarcin ribotoxin by the
      methylotrophic yeast Pichia pastoris: the Lys-Arg motif is required for
      maturation.
AB  - alpha-Sarcin is a ribosome-inactivating protein from the mold Aspergillus
      giganteus. The methylotrophic yeast Pichia pastoris has been transformed with two
      plasmids (pHILD2prealphaS and pHILS1prealphaS), which contain the complete alpha
      sarcin cDNA, including its original fungal leader peptide, under the control of
      yeast alcohol oxidase promoter. The second one is indeed fused to the signal
      sequence of P. pastoris acid phosphatase. The transformed yeasts secreted both
      mature and pro-alpha-sarcin. The presence of this pro-alpha-sarcin in the yeast
      extracellular medium is due to an inefficient recognition of the pro-sequence by
      a putative Kex2p-like endopeptidase. A third plasmid accounting for a single
      mutation of the alpha-sarcin leader peptide was designed to produce a more
      efficient Kex2p recognition motif. This approach resulted in the extracellular
      production of only the mature protein, suggesting the existence of a two-step
      mechanism for processing its leader peptide. This recombinant alpha-sarcin is
      identical to the original fungal protein, according to activity and spectroscopic
      criteria. In addition, pro-alpha-sarcin, which has been characterized for the
      first time, also exhibits ribonucleolytic activity as the mature protein does.
      Therefore, protection of the producing cells against this kind of ribotoxins may
      depend on an efficient recognition of the signal sequence followed by
      translocation of the nascent polypeptide to the endoplasmic reticulum.

PMID- 9535699
TI  - Baculovirus-mediated large-scale expression and purification of a polyhistidine
      tagged rubella virus capsid protein.
AB  - The capsid protein of rubella virus was produced in baculovirus-infected
      Spodoptera frugiperda insect cells, with a polyhistidine affinity tag at the
      carboxy terminus. The RV capsid recombinant protein was produced in a 10-liter
      bioreactor and purified, under nondenaturing conditions, using immobilized metal
      ion affinity chromatography. Immunoblot analyses indicated that the purified
      recombinant protein was intact and migrated with the expected molecular weight.
      The final yield was 5 mg of purified protein per liter of cell culture. Surface
      plasmon resonance was used to investigate the antigenic potential of the
      histidine tagged capsid protein in an antigen-antibody interaction study. A
      specific interaction between the two proteins was shown. Our results suggest that
      this strategy should be useful in interaction studies of other virus-specific
      proteins and antibodies.

PMID- 9535700
TI  - Dog zona pellucida glycoprotein-3 (ZP3): expression in Escherichia coli and
      immunological characterization.
AB  - An internal fragment (978 bp) corresponding to the dog zona pellucida
      glycoprotein-3 (DZP3), excluding the N-terminal signal sequence and the C
      terminal transmembrane-like domain, was amplified by polymerase chain reaction
      from a full-length cDNA clone. The amplified SacI and PstI restricted fragment
      was cloned in-frame downstream of the T5 promoter under lac operator control for
      expression in the pQE-30 vector. Recombinant DZP3 (rec-DZP3) was expressed as a
      polyhistidine fusion protein in Escherichia coli. Optimum expression of rec-DZP3
      was observed at 1.0 mM isopropyl-beta-D-thiogalactopyronoside. Immunoblots with a
      murine monoclonal antibody, MA-451 (raised against porcine ZP3beta-a homologue of
      DZP3 and cross-reactive with dog zona pellucida), revealed a major band of 42
      kDa. Localization studies revealed that the recombinant protein was present only
      in an insoluble intracellular fraction. Further optimization studies revealed
      that the level of expression of rec-DZP3 was significantly higher in Luria broth
      medium containing glycerol rather than glucose and maximum expression was
      observed when cultures were induced during the mid-log phase of growth. Batch
      fermentation with glycerol as the carbon source yielded 30 mg/L of rec-DZP3
      compared to 4 mg/L from a shake flask culture. Immunization of two male rabbits
      with Ni-NTA-purified rec-DZP3 and two female dogs with the rec-DZP3 conjugated to
      diphtheria toxoid generated high antibody titers against rec-DZP3 as determined
      by enzyme-linked immunosorbent assay. Rabbit immune serum reacted with porcine
      ZP3beta but failed to react with porcine ZP3alpha in a Western blot. Moreover,
      antisera when tested by indirect immunofluorescence on dog ovarian sections
      showed positive fluorescence with zona pellucida. The availability of rec-DZP3
      will help in evaluating its efficacy for fertility regulation in stray dogs.

PMID- 9535701
TI  - Expression cloning and biochemical characterizations of recombinant cyclophilin
      proteins from Schistosoma mansoni.
AB  - Recombinant Schistosoma mansoni cyclophilin proteins of the A and the B subtypes
      (SmCYP A and B) were expressed in bacterial cells as histidine- and maltose
      binding fusion proteins and also as nonfused proteins. In addition, S. mansoni
      CYPs were produced in Sf9 insect cells in their natural forms. Purified
      recombinant SmCYP B was found to possess a peptidyl-prolyl cis-trans isomerase
      (PPIase) activity, with a kcat/Km value of 8.2 x 10(5) M-1 s-1. The SmCYP B
      isoform is approximately two to three times more active than SmCYP A. SmCYP B
      specific RNA appears to be more abundant in adult schistosomes than SmCYP A RNA
      in Northern blots. These results support the conclusion that SmCYP B represents
      the major schistosomal CYP. The PPIase-associated activity of both CYPs was
      inhibitable by the immunosuppressive drug cyclosporin A (CsA). We attempt to
      explain differences in PPIase activities and in CsA inhibition by examining
      models of the two CYPs complexed to CsA.

PMID- 9535702
TI  - Increased expression of Brevibacterium sterolicum cholesterol oxidase in
      Escherichia coli by genetic modification.
AB  - To improve expression of Brevibacterium sterolicum cholesterol oxidase in
      Escherichia coli, we utilized the T7lac promoter and modified the gene to encode
      the first 21 amino acids with high-expression E. coli codons. These changes
      resulted in a 60-fold improvement of expression level. N-terminal sequencing
      revealed that the E. coli produced cholesterol oxidase signal peptide is cleaved
      6 amino acids closer to the N-terminus than in B. sterolicum. The recombinant E.
      coli produced protein is composed of 513 amino acids with a calculated Mr of
      55,374. The kinetic rate constants of the recombinant protein and the B.
      sterolicum produced cholesterol oxidase are identical.

PMID- 9535703
TI  - Bacterial expression and characterization of chicken apolipoprotein A-I.
AB  - Apolipoprotein (apo) A-I is a 28-kDa exchangeable apolipoprotein that plays a key
      role in lipoprotein metabolism. It is widely distributed among animal species and
      is rich in alpha-helical secondary structure. Unlike human apoA-I, which
      aggregates in the absence of lipid, chicken apoA-I is monomeric in the lipid-free
      state. To take advantage of this physical characteristic, a bacterial expression
      system for production of recombinant chicken apoA-I has been developed. The cDNA
      encoding chicken apoA-I was cloned into the pET expression vector under the
      regulation of the lac operon and transformed into Escherichia coli. Recombinant
      apoA-I protein recovered from the soluble fraction of the bacterial cell pellet
      was purified to greater than 95% homogeneity by reversed-phase high-performance
      liquid chromatography. Although immunoblot analysis confirmed the identity of the
      overexpressed protein, its migration on denaturing polyacrylamide gel
      electrophoresis was slower than its natural counterpart. To determine if the
      vector-encoded 18 residue pelB N-terminal leader sequence was not cleaved by the
      bacterial leader peptidase, isolated recombinant chicken apoA-I was incubated
      with exogenous leader peptidase. This treatment resulted in an increased
      electrophoretic mobility, with migration to a position corresponding to plasma
      derived chicken apoA-I. Electrospray mass spectrometry indicated a mass of 27,961
      +/- 4 Da, in agreement with that predicted for natural chicken apoA-I. Far-UV
      circular dichroism spectroscopy indicated an alpha-helical content similar to
      apoA-I isolated from chicken plasma, suggesting that the protein is folded in
      solution. Fluorescence studies showed that the wavelength of maximum fluorescence
      emission of the two tryptophan residues in the protein was 331 nm, with no shift
      occurring following complexation with lipid. Recombinant apoA-I was shown to be
      functional in lipoprotein binding as well as to possess an ability to transform
      bilayer vesicles of dimyristoylphosphatidylcholine into discoidal complexes. This
      is the first report of bacterial expression of an avian apoA-I. Increased
      availability and the potential for site-directed mutagenesis of this protein will
      aid in further characterization of apoA-I and the mechanism whereby it functions
      in cholesterol transport.

PMID- 9535705
TI  - Purification, characterization, and crystallization of an N-hydroxyarylamine O
      acetyltransferase from Salmonella typhimurium.
AB  - The N-hydroxyarylamine O-acetyltransferase from Salmonella typhimurium has been
      expressed as a histidine-tagged fusion protein in Escherichia coli and purified
      to apparent homogeneity using single-step immobilized metal ion chromatography.
      Sufficient quantities of the purified protein have been obtained to allow its
      characterization by physical methods including dynamic light scattering and
      electrospray mass spectrometry. The substrate specificity and temperature
      sensitivity of the enzymatic activity have also been assessed. The enzyme has
      been crystallized from sodium, potassium tartrate and X-ray diffraction data have
      been obtained to allow the identification of an orthorhombic unit cell, point
      group P21212, with dimensions a = 137 A, b = 223 A, and c = 105 A. These crystals
      will provide a route to a crystallographic determination of the structure of the
      protein.

PMID- 9535704
TI  - Expression and characterization of human tissue kallikrein variants.
AB  - Human tissue kallikrein is a serine protease implicated in the pathology of
      various inflammatory disorders. As one of the two principal enzymes that generate
      proinflammatory kinin peptides in vivo, tissue kallikrein represents an
      attractive target for therapeutic intervention in diseases such as asthma,
      pancreatitis, and rheumatoid arthritis. Three distinct human tissue kallikrein
      variants, differing in one or two amino acid substitutions, are predicted to
      exist based on genomic or cDNA nucleotide sequences derived from different
      tissues. The effects of these substitutions on the biochemical properties of
      tissue kallikrein are unknown but could, in principle, confer tissue-specific
      functions on the enzyme or affect the clinical utility of specific kallikrein
      inhibitors. All three variants, as well as a deglycosylated derivative, were
      expressed in high yield as recombinant proteins in Pichia pastoris. The
      recombinant kallikrein variants and natural urinary kallikrein all hydrolyzed
      synthetic peptides with similar specificity and efficiency and released kallidin
      from kininogen at comparable rates. Similarly, no significant differences were
      observed in the interactions between kallikrein variants and protein inhibitors
      such as SBTI, alpha1-PI, and aprotinin. We conclude that the known tissue
      kallikrein variants represent allelic variants and are not likely to have tissue
      specific activity related to the amino acid substitutions.

PMID- 9535706
TI  - Recombinant expression, purification, and characterization of three isoenzymes of
      aspartate aminotransferase from Arabidopsis thaliana.
AB  - Five different genes encoding isoenzymes of aspartate aminotransferase (AAT) have
      been identified in the plant Arabidopsis thaliana. cDNA sequences encoding three
      of these AAT isoenzymes, asp1 (mitochondrial), asp2 (cytosolic), and asp5
      (plastid), were manipulated into bacterial expression vectors and the recombinant
      proteins expressed were purified from liquid culture using conventional methods.
      Yields of the purified isoenzymes varied from 11.5 mg/g wet wt cells (AAT5) to
      0.95 mg/g wet wt cells (AAT2), an improvement of more than 1000-fold over typical
      yields of native isoenzymes obtained from plant tissues of other species.
      Analysis of the recombinant proteins on denaturing PAGE gels indicated subunit
      Mrs of between 44 and 45 K. Kinetic parameters (Km and kcat) obtained for all
      four substrates (aspartate, alpha-ketoglutarate, glutamate, and oxaloacetate)
      were consistent with values obtained for native AAT isoenzymes from other plant
      species. Further characterization of the purified recombinant enzymes alongside
      native enzymes from A. thaliana leaf tissue on AAT activity gels confirmed the
      identity of asp1 and asp2 as the mitochondrial and cytosolic AAT genes but
      indicated that asp5 may encode an amyloplastic rather than the chloroplastic
      enzyme.

PMID- 9535707
TI  - Expression, purification, and bioassay of human stanniocalcin from baculovirus
      infected insect cells and recombinant CHO cells.
AB  - Stanniocalcin is a calcium- and phosphate-regulating glycoprotein hormone that
      was first described in fish where it functions in preventing hypercalcemia. Human
      cDNA clones encoding the homolog of stanniocalcin have been recently isolated. In
      this study, the full-length cDNA coding for human stanniocalcin (hSTC) was cloned
      into both baculovirus and CHO expression vectors. Recombinant hSTC was then
      produced efficiently from both baculovirus-infected insect cells and CHO cells in
      large-scale bioreactors. Purification protocols were developed and used to purify
      recombinant hSTC from both sources in four chromatography steps. The hSTCs from
      both expression systems were secreted as glycosylated proteins and as disulfide
      linked homodimers. The results from glycosylation studies indicated that
      stanniocalcin from both sources contained N-linked oligosaccharides but no O
      linked sugars. In an in vivo bioassay based on the inhibition of gill calcium
      transport in fishes, the baculovirus and CHO-expressed protein showed biological
      activity which is dose dependent. The inhibitory effects of hSTC produced from
      both systems were essentially equipotent in fishes, despite the differences in
      glycosylation. Consequently, the precise role of the carbohydrate moiety in
      recombinant hSTC remains to be determined.

PMID- 9535708
TI  - Single-column purification of syncephapepsin--an aspartic proteinase from
      Syncephalastrum racemosum.
AB  - Syncephapepsin is a fungal aspartic proteinase from Syncephalastrum racemosum. By
      using the property of syncephapepsin after having increased activity at higher
      temperature, two rapid purification protocols were developed. In the former case,
      a crude extract was initially diluted fivefold with an activity assay buffer and
      heated at 50 degrees C overnight. In this situation, syncephapepsin would digest
      most of the proteins that the crude extract contained. Subsequently,
      syncephapepsin of the crude extract was precipitated from 50 to 70% of ammonium
      sulfate and the preparation was then directly applied to the Superdex 200 HR FPLC
      column. In this manner, syncephapepsin was rapidly purified to apparent
      homogeneity within 24 h. In this report, an alternative method of purification is
      also provided. Compared with the procedure mentioned above, the heating step was
      proceeded after FPLC chromatography through which the same result was obtained.
      Using cytochrome c and RNase A as substrates, the cleavage sites of both
      substrates were identified by HPLC peptide mapping. The results showed that
      syncephapepsin had a broad specificity. Residues recognized to be cleaved were
      primarily those of trypsin and chymotrypsin and Lys was the most susceptible.

PMID- 9535709
TI  - Recombinant fusion proteins for the industrial production of disulfide bridge
      containing peptides: purification, oxidation without concatamer formation, and
      selective cleavage.
AB  - We report the biotechnical production of peptides of approximately 35-50 amino
      acids in length containing one intramolecular disulfide bridge, using a
      recombinant fusion tail approach. This method fills the technological gap when
      either (a) chemical synthesis fails due to known problematic peptide sequences or
      (b) if simple recombinant expression is unsuccessful due to degradation. The
      fusion tail described here serves several purposes: (i) it enables high
      expression levels in Escherichia coli to be achieved; (ii) it renders the fusion
      protein fairly soluble; (iii) it contains a histidine affinity tag for easy
      purification on Ni-chelate resins, which also serves as a catalyst for the oxygen
      dependent formation of the disulfide bridge; and (iv) it suppresses the formation
      of concatamers during the oxidation process through steric hindrance. The
      purified fusion protein is then immobilized on a reversed phase column for two
      purposes: (i) chemical cleavage of the fusion tail by cyanogen bromide and (ii)
      subsequent purification of the peptide. A very hydrophilic fusion partner is
      required so that immobilization on the reversed phase column always occurs due to
      the peptide. Sensitive hydrophobic residues are thereby protected from the
      cleavage reagent while the cleaved hydrophilic fusion tail is easily separated
      from the hydrophobic peptide. The method is exemplified by eight peptides
      representing an immunodominant epitope of the human immunodeficiency virus, but
      may be useful for a significant variety of similar peptides.

PMID- 9535710
TI  - Expression and purification of the alpha-subunit of eukaryotic initiation factor
      eIF2: use as a kinase substrate.
AB  - The alpha-subunit of eukaryotic initiation factor eIF2 (eIF2alpha) plays an
      important role in the regulation of mRNA translation through modulation of the
      interaction of eIF2 and a second initiation factor, eIF2B. The interaction of the
      two proteins is regulated in vivo by phosphorylation of eIF2alpha at Ser51. In
      the present study, rat eIF2alpha was expressed in Sf21 cells using the
      baculovirus expression system. The recombinant protein was purified to >90%
      homogeneity in a single immunoaffinity chromatographic step. The protein was free
      of endogenous eIF2alpha kinase activity and was rapidly phosphorylated by the
      eIF2alpha kinases HCR and PKR. A variant of eIF2alpha in which the
      phosphorylation site was changed to Ala was also expressed and purified. The
      variant eIF2alpha was not phosphorylated by either HCR or PKR, demonstrating that
      the kinases specifically phosphorylate the correct site in the recombinant
      protein even in the absence of the other two subunits of the protein. In summary,
      a rapid and inexpensive method for obtaining eIF2alpha has been developed. Use of
      the wildtype and variant forms of eIF2alpha to measure eIF2alpha kinase activity
      in cell and tissue extracts should greatly facilitate examination of the
      regulation of mRNA translation under a variety of conditions.

PMID- 9535711
TI  - Purification of cytochrome b5 from pig testis microsomes by isoelectric focusing
      in an immobiline pH gradient.
AB  - Testicular cytochrome b5 was purified by a procedure including preparative
      isoelectrofocusing. The cytochrome b5 was determined to have an isoelectric point
      of 4.45 on analytical isoelectric focusing. The purified cytochrome b5 was found
      to be homogeneous and its molecular weight was estimated to be 16,000 on
      polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. The
      oxidized and reduced forms of the purified preparation exhibited absorption
      spectra of a typical cytochrome b5. A 69-fold purification was achieved with an
      overall yield of 6.2%. Following preparation of the microsomes, the purification
      is accomplished by a two-step procedure utilizing column chromatography and
      preparative isoelectric focusing.

PMID- 9535713
TI  - Cytokine-receptor complexes as chaperones for nuclear translocation of signal
      transducers.
AB  - A variety of ligands that include interleukins, interferons, and growth hormones
      activate STAT transcriptions factors. When activated, STATs are translocated to
      the nucleus apparently through the well described importin/Ran system where they
      activate target genes. Molecules utilizing this nuclear import system require
      specific nuclear localization sequences (NLSs). Paradoxically, such NLSs are not
      identifiable on STATs, raising the question of how they are imported into the
      nucleus. Surprisingly, most ligands and/or receptors that signal through STATs
      contain putative NLSs, and where examined either ligand or receptor undergo
      nuclear translocation. We hypothesize that these ligands and/or their receptors
      serve as chaperones in the nuclear translocation of STATs, and that they may be
      directly involved in signal transduction. Using IFN gamma as a model system we
      provide a possible mechanism for how this direct role is fulfilled. A C-terminal
      domain of IFN gamma has been identified that contains a functional NLS. Besides
      the fact that this domain, and the NLS in particular, is crucial for the
      biological properties of IFN gamma, a peptide encompassing this domain is
      sufficient to induce an antiviral state. Moreover, this domain interacts
      exclusively with an internal cytoplasmic domain of a subunit of the receptor
      complex in a region that is directly involved in the recruitment and activation
      of the elements of the JAK/STAT pathway. We suggest that this novel mode of
      receptor recognition and activation may be a driving force for nuclear
      translocation of molecules like STATs that are associated with the ligand
      receptor complex.

PMID- 9535714
TI  - Up-regulation of COX2 expression by uni-axial cyclic stretch in human lung
      fibroblast cells.
AB  - The effect of uni-axial cyclic mechanical stretch on the expression of
      cyclooxygenases (COX) was investigated in a human lung fibroblast cell line (TIG
      1). In response to uni-axial cyclic stretch, the level of COX2 mRNA significantly
      increased and peaked at 3 h (9.09 +/- 3.82-fold, mean +/- standard error, n = 6,
      compared with that at 1 h). The level of the expression of COX2 protein peaked at
      6 h, whereas the level of COX1 protein was not significantly changed. The
      involvement of stretch-activated (SA) channel was investigated in the stretch
      induced COX2 production. The application of Gd3-, a blocker for SA channel, or
      the removal of extracellular Ca2+ inhibited the production of COX2 mRNA without
      any effect on the production of COX1 or GAPDH mRNA. These data strongly suggest
      that COX2 expression is up-regulated by uni-axial cyclic stretch via the
      activation of SA channel in human lung fibroblasts.

PMID- 9535715
TI  - The 24-kDa subunit of the bovine mitochondrial NADH:ubiquinone oxidoreductase is
      a G protein.
AB  - Based on the results obtained from GTP overlay assay, immunoprecipitation, two
      dimensional electrophoresis and radiolabeled GTP binding, we provide evidence
      that the bona fide subunit of Complex I, the long known 24 kDa protein is a G
      protein. Bacterially expressed 24 kDa protein with additional N-terminal
      methionine and alanine residues or naturally expressed truncated isoform fail to
      bind GTP suggesting that secondary modification/ processed N-terminal end is
      necessary for GTP binding. Competitive inhibition of binding of radiolabeled GTP
      to electroblotted 24 kDa protein with unlabelled nucleotides showed that the
      protein binds GTP and GDP with high affinity in presence of Mg2+, and has
      decreased to very low affinity for ITP, CTP, GMP and UTP. A comparative binding
      of [gamma-35S]-GTP to Complex I and 24 kDa protein (electroblotted) suggests that
      the GTP binding in the native Complex is solely due to 24 kDa protein. Further,
      four fold difference in the binding affinities between native Complex I and 24
      kDa protein (electroblotted) as seen by Scatchard analysis of the binding data
      indicates that protein undergoes structural rearrangement in Complex I bound
      form, that presumably triggers divalent cation dependent GTPase activity in
      native complex. We were unable to detect the effect of GTP/ GDP on the
      ubiquinone/ferricyanide reductase activity. Since the subunit is found missing in
      tissues affected by mitochondrial respiratory chain diseases, we presume that the
      subunit has regulatory role in the Complex I function in the electron transport
      chain.

PMID- 9535716
TI  - Phosphatidylinositol 3-kinase inhibitors block aortic smooth muscle cell
      proliferation in mid-late G1 phase: effect on cyclin-dependent kinase 2 and the
      inhibitory protein p27KIP1.
AB  - In the present study, we investigated the involvement of phosphatidylinositol 3
      kinase (PI 3-kinase) activity in the progression of vascular smooth muscle cells
      (VSMCs) throughout the G1 phase of cell cycle. Addition of two selective
      inhibitors of PI 3-kinase, LY 294002 or wortmannin, to quiescent VSMCs prevented
      serum-induced DNA synthesis in a dose-dependent manner with IC50 of 8.7 +/- 2.0
      microM and 53.9 +/- 8.5 nM, respectively. Time course studies revealed that the
      two PI 3-kinase inhibitors blocked VSMC proliferation in mid-late G1 phase, about
      6 h before the G1/S transition. This G1 growth arrest was due, at least in part,
      to the reduction of the CDK2 associated kinase activity resulting mainly from the
      upregulation of the inhibitory protein p27KIP1.

PMID- 9535718
TI  - Angiogenic stimuli are essential for survival of vascular endothelial cells in
      three-dimensional collagen lattice.
AB  - Cultured vascular endothelial cells derived from bovine aorta (BAECs) can survive
      and proliferate in the condition of two-dimensional monolayer culture in the
      presence of serum without any specific growth factors. When BAECs were embedded
      in collagen lattice, they underwent apoptotic death within 2 days unless the
      cultures were repeatedly supplied with angiogenic growth factor such as
      fibroblast growth factor-2 (FGF-2). Supplementation with FGF-2 induced
      endothelial cell differentiation, resulting in capillary-like tube formation
      inside collagen lattice. Following tube formation, withdrawal of FGF-2 induced
      disruption of the tube structures associated with the characteristic apoptotic
      cell death. These effects of FGF-2 were regulated by tyrosine phosphorylation,
      but not mediated through protein kinase C pathway. This model of endothelial cell
      apoptosis inside collagen lattice may represent in vivo endothelial cell-matrix
      interaction during angiogenesis process, indicating that apoptotic death of
      endothelial cells may regulate angiogenesis and the regression of vessels.

PMID- 9535717
TI  - Differential effect of alpha-lactalbumin on beta-1,4-galactosyltransferase IV
      activities.
AB  - We isolated a human cDNA clone encoding beta-1,4-galactosyltransferase (beta-1,4
      GalT IV) which shares 37% identity with previously characterized mammalian beta
      1,4-GalT (beta-1,4-GalT I). By transfection of the full length cDNA into Sf-9
      cells and assay of the cell homogenates, higher beta-1,4-GalT activity toward
      GlcNAc beta-S-pNP was obtained, and its activity was modulated with alpha
      lactalbumin, while no lactose synthetase activity was detected in the presence of
      alpha-lactalbumin. Northern blot analysis using total and poly (A)+ RNA
      preparations revealed that the expression level of beta-1,4-GalT IV transcript is
      low and relatively constant while that of beta-1,4-GalT I transcript is
      dramatically increased in the mouse mammary gland during lactation. These results
      indicate that beta-1,4-GalT IV can interact with alpha-lactalbumin but has no
      lactose synthetase activity.

PMID- 9535720
TI  - Overexpression of hepatitis delta antigen protects insect cells from baculovirus
      induced cytolysis.
AB  - Hepatitis delta virus (HDV) is a human pathogen causing fulminant hepatitis and
      liver cirrhosis. HDV has a circular single-stranded RNA genome, which encodes
      only a single protein, hepatitis delta antigen (HDAg), from the antigenomic
      strand. Although the functional roles of HDAg have been extensively studied, the
      molecular mechanism of persistent infection and pathogenesis of HDV are not yet
      understood. Here we report that overexpressed HDAg protects cells from death in
      baculovirus-infected insect cells. Using both wild-type and recombinant
      baculovirus-infected insect cells, we have demonstrated that HDAg inhibited wild
      type baculovirus-induced cytolysis and thus extended the survival of virus
      infected insect cells. By deletion analysis, we show that N-terminal 25 amino
      acids are essential for this function. From these data, we suggest that HDAg may
      play a major role in persistent infection of HDV.

PMID- 9535719
TI  - Nitric oxide protects cardiomyocytes against tert-butyl hydroperoxide-induced
      formation of alkoxyl and peroxyl radicals and peroxidation of phosphatidylserine.
AB  - We studied protective effects of nitric oxide against tert-butyl hydroperoxide
      induced oxidative damage to cardiac myocytes. Two distinct free radicals species-
      alkoxyl radicals associated with non-heme iron catalytic sites and myoglobin
      protein-centered peroxyl radicals--were found in low-temperature EPR spectra of
      cardiac myocytes exposed to t-BuOOH. The t-BuOOH-induced radical formation was
      accompanied by site-specific oxidative stress in membrane phospholipids
      (peroxidation of phosphatidylserine) assayed by fluorescence HPLC after metabolic
      labeling of cell phospholipids with oxidation-sensitive cis-parinaric acid. An NO
      donor, (Z)-1-[N-(3-ammonio-propyl)-N-(n-propyl) amino]-diazen-1-ium-1,2-diolate],
      protected cardiac myocytes against tert-butyl hydroperoxide-induced: (i)
      formation of non-protein- and protein-centered free radical species and (ii)
      concomitant peroxidation of phosphatidylserine. Thus nitric oxide can act as an
      effective antioxidant in live cardiomyocytes.

PMID- 9535721
TI  - LOE 908 blocks delayed rectifier type potassium channels in PC12 cells and
      cortical neurons in culture.
AB  - The effects of (R,S)-(3,4-dihydro-6,7-dimethoxy-isoquinoline-1-yl)-2- phenyl-N,N
      di-[2-(2,3,4-trimethoxyphenyl)ethyl]-acetamide (LOE 908) were studied on K+
      currents in undifferentiated cells from a phaeochromocytoma cell line (PC12), in
      cortical neurons from rat in primary culture, in a rat blood lymphoma cell line
      (RBL-1) and in a kidney cell line (BHK21). In PC12 cells delayed rectifier K+
      currents measured in the whole-cell mode of the patch clamp technique were almost
      completely blocked by 10 microM LOE 908. The IC50 value was 0.7 microM and the
      Hill coefficient 0.8. After washout of the inhibitor about 80% of the current
      recovered. In rat cortical neurons in primary culture LOE 908 inhibited
      tetraethylammonium (TEA, 10 mM)-sensitive delayed rectifying K+ currents (LOE
      908: 1 microM, 61 +/- 25% inhibition; 10 microM 103 +/- 19% inhibition). In
      contrast to the inhibitory action of LOE 908 on delayed rectifying K+ currents,
      Ca(2+)-activated potassium currents in BHK21 cells were only inhibited by 25 +/-
      5% (10 microM LOE 908, n = 5) and no effect of LOE 908 was found on inward
      rectifying K+ currents in RBL-1 cells. We conclude that LOE 908 is a K+ channel
      blocker with selectivity for delayed outward rectifying K+ channels.

PMID- 9535722
TI  - IL-13 induces tyrosine phosphorylation of phospholipase C gamma-1 following IRS-2
      association in human monocytes: relationship with the inhibitory effect of IL-13
      on ROI production.
AB  - Here we analysed the involvement of tyrosine phosphorylation in the regulation of
      the initial molecular events induced by IL-13 to modulate TPA-triggered reactive
      oxygen intermediates (ROI) production. Our data indicate that treatment of
      monocytes with a protein tyrosine kinase inhibitor (herbimycin A) prevents IL-13
      induced cAMP accumulation and subsequent ROI inhibition. We have previously
      demonstrated that cAMP accumulation depends on inositol phosphates hydrolysis
      (InsPs) and intracellular Ca2+ mobilisation. The inhibition of InsPs and
      intracellular Ca2+ release by herbimycin A suggests a primary role of tyrosine
      kinases upstream PLC activation. We further specify that IL-13 stimulates PLC
      gamma 1 and IRS-2 tyrosine phosphorylation in human monocytes. We demonstrate for
      the first time that IL-13 induces the association of IRS-2 with PLC-gamma 1. We
      proposed here that PLC-gamma 1 is a new candidate recruited by IRS-2.

PMID- 9535723
TI  - DNA bending is induced by binding of the peroxisome proliferator-activated
      receptor gamma 2 heterodimer to its response element in the murine lipoprotein
      lipase promoter.
AB  - The peroxisome proliferator activated receptor gamma 2 (PPAR gamma 2) is a
      critical transcriptional regulator of adipogenesis. Lipoprotein lipase is one of
      the earliest genes induced following exposure of pre-adipocytes to PPAR gamma 2
      ligands such as the thiazolidinediones. A unique PPAR gamma 2 DNA recognition
      element was mapped to the region between -171 to -149 bp of the murine LPL
      promoter, based on transfection analysis of deletion constructs and gel retention
      assays using bacterially expressed, affinity purified recombinant proteins.
      Circular permutation analysis determined that binding of the PPAR gamma
      2/retinoic acid X receptor (RXR) heterodimer to its LPL promoter recognition
      element induced DNA bending at an angle of approximately 46 degrees. Parallel
      studies using an optimal PPAR recognition element obtained a comparable bending
      angle of 56 degrees. This is the first demonstration that binding of a PPAR
      protein to its recognition element causes a distortion of the DNA configuration.
      It indicates that PPAR gamma 2 utilizes a common mechanism shared by other
      nuclear hormone receptor proteins reported to induce bending at their DNA binding
      sites.

PMID- 9535724
TI  - Dietary conjugated linoleic acid normalizes impaired glucose tolerance in the
      Zucker diabetic fatty fa/fa rat.
AB  - Conjugated linoleic acid (CLA) is a naturally occurring fatty acid which has anti
      carcinogenic and anti-atherogenic properties. CLA activates PPAR alpha in liver,
      and shares functional similarities to ligands of PPAR gamma, the
      thiazolidinediones, which are potent insulin sensitizers. We provide the first
      evidence that CLA is able to normalize impaired glucose tolerance and improve
      hyperinsulinemia in the pre-diabetic ZDF rat. Additionally, dietary CLA increased
      steady state levels of aP2 mRNA in adipose tissue of fatty ZDF rats compared to
      controls, consistent with activation of PPAR gamma. The insulin sensitizing
      effects of CLA are due, at least in part, to activation of PPAR gamma since
      increasing levels of CLA induced a dose-dependent transactivation of PPAR gamma
      in CV-1 cells cotransfected with PPAR gamma and PPRE X 3-luciferase reporter
      construct. CLA effects on glucose tolerance and glucose homeostasis indicate that
      dietary CLA may prove to be an important therapy for the prevention and treatment
      of NIDDM.

PMID- 9535725
TI  - Abrogation of Fas-induced fulminant hepatic failure in mice by hepatocyte growth
      factor.
AB  - Excessive activity of the Fas system in the liver is an essential event and
      contributor to fulminant hepatic failure, whose prognosis is extremely poor with
      high mortality due to lack of effective therapy. Administration of agonistic anti
      Fas antibody to mice rapidly led to massive liver apoptosis and fulminant hepatic
      failure. In contrast, administration of human recombinant hepatocyte growth
      factor (HGF) abrogated Fas-induced massive liver apoptosis and the lethal hepatic
      failure. Addition of anti-Fas antibody to hepatocytes in primary culture induced
      cell death, but Fas-mediated cell death was potently suppressed by HGF. HGF
      strongly induced Bcl-xL expression and subsequently blocked Fas-mediated
      signaling pathway upstream of CPP32 in the liver. These results implicate a
      potential therapeutic usage of HGF for treatment of fulminant hepatic failure.

PMID- 9535727
TI  - Isolation of a bioactive Ca(2+)-mobilizing complex lipid from bovine vitreous
      body.
AB  - Vitreous body extracts show a potent Ca(2+)-mobilizing activity on fibroblast
      cells. This Ca2+ signal is complex, and due to the presence of two different
      bioactive substances. The first one was identified as acid FGF. The second one
      was shown to be a low molecular weight substance identified as a complex lipid by
      a combination of chromatographic and biochemical data. This finding raises the
      possibility that non-classical substances with growth factor-like activity might
      play a role in the regulation of proliferative processes in the eye.

PMID- 9535726
TI  - Estrogen inhibits phorbol ester-induced I kappa B alpha transcription and protein
      degradation.
AB  - Estrogen (E2) is known to prevent bone loss and the mechanism is, at least in
      part, mediated by inhibition of expression of cytokines such as interleukin-6 (IL
      6). Expression of IL-6 is tightly regulated and the transcription factor NF kappa
      B can upregulate IL-6 gene expression by binding to its promoter region. NF kappa
      B is kept in an inactive state by associating with its cytoplasmic inhibitor I
      kappa B alpha. Upon mitogenic stimulation, I kappa B alpha becomes
      phosphorylated, followed by a rapid protein degradation. As a result, NF kappa B
      is released and translocate to the nucleus where DNA binding occurs. It has been
      shown that E2 treatment downregulates mitogen-induced IL-6 expression by
      inhibiting NF kappa B activity. Here, we sought to determine whether E2 regulates
      IL-6 gene expression by modulating the levels of I kappa B alpha. Our results
      show that E2 treatment almost completely inhibits phorbol ester-induced I kappa B
      alpha protein degradation. In addition, E2 inhibits phorbol ester-stimulated I
      kappa B alpha gene expression. Taken together, our results suggest that E2
      maintains steady state levels of I kappa B alpha upon mitogen stimulation,
      resulting in inhibition of NF kappa B activation and IL-6 gene expression. This
      may explain the protective effect of E2 on bone loss.

PMID- 9535728
TI  - EH domain-dependent interactions between Eps15 and clathrin-coated vesicle
      protein p95.
AB  - The endocytic protein Eps15 contains three copies of the EH domain, a protein
      module thought to function in protein-protein interactions. Using overlay assays
      with an Eps15 EH domain fusion protein, we have now identified a protein of 95
      kDa (p95) as a major EH domain-binding partner in a wide variety of tissues. The
      amino acids asparagine-proline-phenylalanine (NPF) form the core of an EH domain
      binding motif and three NPF repeats are found in the endocytic protein
      synaptojanin-170. We have confirmed previous studies indicating that synaptojanin
      170 is an EH domain-binding protein, and have used peptide blocking experiments
      to demonstrate that the interaction is mediated through the NPF repeats.
      Interestingly, the same peptide also blocks EH domain-binding to p95. Finally, we
      have shown that p95 is enriched on clathrin-coated vesicles, suggesting an
      endocytic role for the protein. These data support an important role for EH
      domain-NPF motif interactions in endocytosis.

PMID- 9535729
TI  - Long-term exposure to retinoic acid induces the expression of IRK1 channels in
      HERG channel-endowed neuroblastoma cells.
AB  - The modulation of inward K+ conductances was studied during neuronal
      differentiation of human SH-SY5Y neuroblastoma cells. Under standard culture
      conditions, these cells express the herg gene, and the HERG current is the main
      inward K+ current regulating their Vrest. After 10-20 days exposure to Retinoic
      Acid (RA), SH-SY5Y cells showed, in addition to HERG currents, a novel current
      characterized by inward rectification, dependence on the extracellular K+
      concentration, and blockade by Cs+ and Ba2+, the main features of the IRK1
      current. The appearance of this current is accompanied by a strong
      hyperpolarisation of Vrest. RT-PCR experiments confirmed that a transcript of the
      IRK1 (Kir 2.1) gene actually appears in SH-SY5Y cells treated for 10-20 days with
      RA. On the whole, data here presented demonstrate that RA-induced neuronal
      differentiation of neuroblastoma cells is accompanied by the switch from a HERG
      driven to a IRK1-driven control of Vrest, similarly to what happens in normal
      differentiating neurons; however, in tumor cells, this switch does not imply the
      abolition of HERG channel expression.

PMID- 9535730
TI  - Protein-lipid interactions and enzyme requirements for light subtype generation
      on cycling reconstituted surfactant.
AB  - Surfactant convertase is required for conversion of heavy density (H) natural
      surfactant to light density (L) subtype during cycling in vitro, a technique that
      reproduces surfactant metabolism. To study mechanisms of H to L conversion, we
      prepared liposomes of dipalmitoylphosphatidylcholine (DPPC) and
      phosphatidylglycerol (PG), or the phospholipids (PL) in combination with either
      surfactant protein A (SP-A), surfactant protein B (SP-B), or both SP-A and SP-B.
      Phospholipids alone showed time-dependent conversion from heavy to light subtype
      on cycling in the absence of convertase, which was decreased by adding SP-B, but
      not SP-A, to phospholipids (p < 0.01 for PL+SP-B, or PL+SP-A+SP-B vs. PL, or
      PL+SP-A). The ultrastructure, surface activity, buoyant density, and L subtype
      generation on cycling PL+SP-A+SP-B with partially purified convertase or with
      phospholipase D were similar to those of natural TM. In conclusion, a
      reconstituted surfactant mimics the behavior of natural surfactant on cycling,
      and reveals that interaction of SP-B with phospholipids decreases L subtype
      generation. In addition, esterase/ phospholipase D activity is required for
      conversion of heavy to light subtype on cycling.

PMID- 9535731
TI  - Modification of the pH dependence of animal and plant transport ATPases by
      sulfated polysaccharides.
AB  - The effects of heparin and dextran sulfate 8,000 on two isoforms of the
      sarco/endoplasmic reticulum Ca(2+)-ATPase of different animal tissues and on the
      corn root H(+)-ATPase were examined. In the absence of sulfated polysaccharides
      the pH profile's of the three transport ATPases were quite different, but after
      the addition of heparin or dextran sulfate 8,000 the pH profiles of the three
      enzymes became similar, all showed maximal activity at pH 7.0. Potassium and
      sodium antagonized the effects of sulfated polysaccharides on the three transport
      ATPases, but the antagonism was considerably reduced at acidic pH values.

PMID- 9535732
TI  - Evidence for a 1 alpha,25-dihydroxyvitamin D3 receptor/binding protein in a
      membrane fraction isolated from a chick tibial fracture-healing callus.
AB  - Previous biological studies have implicated two vitamin D metabolites, 1
      alpha,25(OH)2-vitamin D3[1 alpha,25(OH)2-D3] and 24R,25(OH)2-vitamin D3
      [24R,25(OH)2D3] in the process of skeletal fracture-healing. While a nuclear
      receptor for 1 alpha,25(OH)2D3 is known to be present in osteoblast and absent in
      osteoclast cell lines, no systematic study has been carried out on the callus
      tissue which is formed during fracture-healing. The present report shows that a
      binding protein/receptor for 1 alpha,25(OH)2D3 resides both in a postnuclear
      membrane fraction and in a high speed cytosol fraction of the callus tissue
      obtained 10 days after imposition of a tibial fracture. The dissociation
      constant, KD, for 1 alpha,25(OH)2D3 was 0.83 +/- 0.34 M and 0.66 +/- 0.38 nM
      respectively, for the membrane and cytosol fractions. Results from a panel of
      steroid competition assays indicate that both receptor/binding proteins greatly
      prefer 1 alpha-hydroxylated ligands as compared to 1 alpha-deoxy or 24
      hydroxylated ligands. The presence of 1 alpha,25(OH)2D3 receptors in the fracture
      healing callus is consistent with the known biological effects of the metabolite
      on the fracture-healing process.

PMID- 9535733
TI  - Effects of proteasomal inhibitors on the maturation of the insulin proreceptor:
      an anatomical paradox.
AB  - Inhibitors of proteasomal functions Carbobenzoxy-L-leucyl-L-leucyl-L-leucinal
      (MG132) and Carbobenzoxy-L-isoleucyl-gamma-t-butyl-L-alanyl-L-leucinal (PSI) were
      found to inhibit the conversion of the Insulin proreceptor to its mature alpha
      and beta subunits. By contrast no effect of these inhibitors was found on 125-I
      insulin binding, internalization and degradation. Since the insulin proreceptor
      is an integral membrane protein that is compartmentally separated from the
      cytoplasmic 26S proteasome, the inhibition of the normal biosynthetic processing
      of the insulin proreceptor presents an anatomical paradox.

PMID- 9535734
TI  - Structural studies of synthetic peptide fragments derived from the HIV-1 Vpr
      protein.
AB  - Vpr, one of the accessory gene products of the human immunodeficiency virus-1
      (HIV-1) genome, exhibits diverse biological characteristics. Vpr functions as a
      transcriptional activator of HIV and heterologous promoters. It is capable of
      arresting cells in cell cycle progression and plays a crucial role in the
      infection of macrophages. Despite the wealth of information available on the
      biological aspects of Vpr, the structure of Vpr remains poorly understood. To
      gain insight into the structure-function relationship of Vpr, peptides
      corresponding to putative helical regions of Vpr were synthesized and their
      structures determined by circular dichroism (CD) spectroscopy. The CD studies
      confirmed the predicted helical structures of these peptides. Based on the data,
      a hypothetical model for the structure of Vpr was proposed which displays an anti
      parallel alpha-helix core structure reminiscent of a helix-loop-helix motif.
      These findings are consistent with the results from mutational studies of Vpr and
      provide a plausible structural basis to further investigate the multiple
      functions of Vpr as a viral protein.

PMID- 9535735
TI  - Induction of hepatic cytochrome P-450 by phenobarbital in semi-aquatic frog (Rana
      pipiens).
AB  - Hepatic microsomal cytochrome P450 (equivalent to rat P4502B1 isozymic form, a
      CYPIIB gene product) can be induced by pentobarbital (PB) in the adults of the
      semiaquatic frog, Rana pipiens (as in other terrestrial vertebrates), but not in
      adults of the aquatic frog Xenopus laevis or in bluegill sunfish (Lepomis
      macrochirus). The activity of PB-induced P450 (2B1) towards aldrin and
      pentoxyresorufin increases respectively by about 2- and 10-fold. This enzyme is
      not inducible during larval and postlarval stages of R. pipiens. However,
      cytochrome P4501A1 (CYPIA1 gene product) is inducible by beta-naphthoflavone in
      all these species. Both CYPIA and CYPIIB genes are expressed, as determined by
      the catalysis of their protein products, during larval, postlarval, and adult
      stages of R. pipiens. The concentration of P450 increases slightly during the
      postlarval stages until the adult stage, ready to migrate to land, is reached.
      This increase seems to be mostly due to 2B1-type cytochrome P450 as judged by a
      large increase in aldrin epoxidase but not of 7-ethoxyresorufin O-deethylase
      activity. It is hypothesized that the evolution of true terrestrialness, and not
      the evolution of air-breathing lungs alone, is required for the transcriptional
      activation of CYPIIB gene by PB.

PMID- 9535736
TI  - Involvement of Mac-1-mediated adherence and sphingosine 1-phosphate in survival
      of phorbol ester-treated U937 cells.
AB  - Phorbol esters exert a dual function in human leukemia cells, induction of
      differentiation and activation of integrin-mediated functions. Here we have shown
      that the plastic adherence of phorbol ester-treated U937 cells is mediated by
      expression of integrin Mac-1 (CD11b/CD18) on the cell surface and that these
      adherent cells exhibit anoikis (apoptosis when adherent cells are detached or
      adherence is inhibited). We used U937-derived clones overexpressing either
      antisense RNAs antisense to CD11b and CD18 mRNAs or mRNA from a truncated mutant
      CD11b gene. We have also shown that apoptosis in non-adherent cells or anoikis
      was mediated by sphingosine and that survival of adherent cells was achieved by a
      shift of the dynamic balance between sphingosine and sphingosine 1-phosphate
      toward the latter by adherence-activated sphingosine 1-kinase.

PMID- 9535737
TI  - The presenilin 1 mutation (M146V) linked to familial Alzheimer's disease
      attenuates the neuronal differentiation of NTera 2 cells.
AB  - Mutations in presenilin 1 (PS1) gene are the major cause of early-onset familial
      Alzheimer's disease. The biological functions of PS1 remain elusive, although
      accumulating evidence suggests that PS1 may play an important role in development
      and differentiation. To learn about the significance of PS1 in the
      differentiation of neuronal cells, we established NTera 2 (NT2) cell lines stably
      expressing wild-type (wt) or M146V mutant human PS1, and compared the
      differentiation of both types of cell lines into postmitotic neurons upon
      retinoic acid (RA) treatment. After 25 days of RA treatment, a significant
      proportion of cells differentiated into neurons in NT2 cells expressing wt PS1
      (27.7% of total cells), which was comparable to that in untransfected cells,
      whereas very few cells differentiated into neurons in NT2 cells expressing M146V
      mutant PS1 (2.6% of total cells). These results suggest that mutant PS1
      attenuates the potentials of NT2 cells to differentiate into neurons.

PMID- 9535738
TI  - Mutations which abolish phosphorylation of the TRAF-binding domain of TNF
      receptor 2 enhance receptor-mediated NF-kappa B activation.
AB  - We demonstrate that a 41 amino acid region (amino acids 379 to 419) in the
      cytoplasmic domain of tumor necrosis factor receptor 2 (TNFR2) is phosphorylated
      by unidentified kinase(s) both in vitro and in vivo. This domain (denoted x1c)
      corresponds almost exactly to the previously identified TRAF-binding domain and
      is by itself sufficient as a substrate for phosphorylation. In addition, the x1c
      domain is also crucial for TNFR2-mediated NF-kappa B activation. The cytoplasmic
      domain of TNFR2 lacks tyrosines, and conversion of all 12 potential serine and
      threonine phosphorylation targets in x1c to alanines either had no effect on NF
      kappa B activation or resulted in enhanced NF-kappa B activity, depending on the
      structural context of x1c. The results show that while the TRAF-binding domain of
      TNFR2 is a major target of kinases, its phosphorylation is not required for NF
      kappa B activation. Our data moreover suggest that phosphorylation of x1c
      negatively regulates the activation of NF-kappa B.

PMID- 9535739
TI  - Identification of phosphorylated proteins associated with the fibroblast growth
      factor receptor type I during early Xenopus development.
AB  - Signaling through the FGF receptor (FGFR) is required for mesoderm induction in
      Xenopus. Some of the downstream signaling molecules implicated in this
      developmental process include Ras, Raf and MAP kinase. In a previous report, we
      demonstrated that PLC gamma 1, Grb-2, SOS and Nck were associated with activated
      FGFR1s in a signaling complex in Xenopus blastulae. In addition, several
      unidentified phosphotyrosylproteins were present in the FGFR1 complex. Here we
      identify three of these proteins as Ras-GAP, the p85 of P13'K and SHP2, while
      demonstrating that c-Src and She were not associated with the FGFR1. Furthermore,
      we show that three additional phosphotyrosylproteins from the FGFR1 complex
      specifically bound to the adaptor molecule Nck.

PMID- 9535740
TI  - Expression of CYP19 (aromatase) mRNA in the human temporal lobe.
AB  - The conversion of androgens to estrogens by CYP19 (cytochrome P450AROM,
      aromatase) is an important step in the mechanism of androgen action in the brain.
      CYP19 expression has been demonstrated in various animal species, but studies in
      human postnatal brain tissue are lacking. Therefore, we investigated CYP19 mRNA
      expression in human temporal lobe tissues. We studied biopsy materials removed at
      neurosurgery from 34 women, 32 men and 10 children with temporal lobe epilepsy.
      Quantification of CYP19 mRNA was achieved by nested competitive reverse
      transcription-PCR. CYP19 mRNA concentrations did not differ significantly between
      women (2.6 +/- 0.6 arbitrary units, aU; mean +/- SEM) and men (1.6 +/- 0.3 aU)
      nor between cerebral cortex tissue (2.0 +/- 0.4 aU) and subcortical white matter
      tissue of adults (2.4 +/- 0.7 aU), but they were significantly lower in cerebral
      cortex specimens of children (0.9 +/- 0.6 aU) than in those of adults (p < 0.02).
      In conclusion, CYP19 mRNA is expressed in the temporal lobe of children and
      adults. CYP19 mRNA concentrations are significantly lower in specimens of
      children than in those of adults.

PMID- 9535741
TI  - A putative voltage-gated sodium channel alpha subunit (PpSCN1) from the hydrozoan
      jellyfish, Polyorchis penicillatus: structural comparisons and evolutionary
      considerations.
AB  - Extant cnidarians are probably the simplest metazoans with discrete nervous
      systems and rapid, transient voltage-gated currents carried exclusively by Na+
      ions. Thus cnidarians are pivotal organisms for studying the evolution of voltage
      gated Na+ channels. We have isolated a full-length Na+ channel alpha subunit cDNA
      (PpSCN1) from the hydrozoan jellyfish, Polyorchis penicillatus, that has one of
      the smallest known coding regions of a four domain Na+ channel (1695 amino
      acids). Homologous residues that have a critical bearing on the selectivity
      filter, voltage-sensor and binding sites for tetrodotoxin and lidocaine in
      vertebrates and most invertebrates differ in cnidarians. PpSCN1 is not
      alternatively-spliced and may be the only pore-forming alpha subunit available to
      account for at least three electrophysiologically distinct Na+ currents that have
      been studied in P. penicillatus.

PMID- 9535742
TI  - Reduction of 13-hydroperoxy-9,11-octadecadienoic acid by dopamine-melanin.
AB  - The effect of dopamine-melanin (DA-melanin), synthetic model of neuromelanin, on
      the stability of 13-hydroperoxyoctadecadienoic acid (13-HPODE) has been
      investigated using a reverse-phase high-performance liquid chromatography (HPLC)
      with UV detection. It was found that DA-melanin effectively accelerated the
      decomposition of 13-HPODE, both in the absence and in the presence of ferrous
      ions. The disappearance of 13-HPODE was accompanied by the formation of 13
      hydroxyoctadecadienoic acid (13-HODE). The results obtained indicate that DA
      melanin is able to reduce linoleic acid hydroperoxide to its stable hydroxyl
      derivative. The fatty acid hydroperoxide-reducing ability of DA-melanin appears
      to play an important role in the antioxidative activity of neuromelanin in the
      process of lipid peroxidation.

PMID- 9535743
TI  - Reinvestigation of the functions of the hydrophobic segment of Jem1p, a yeast
      endoplasmic reticulum membrane protein mediating nuclear fusion.
AB  - Jem1p is a DnaJ-like protein of the yeast ER membrane, which is required for
      nuclear membrane fusion during mating. We have determined the position of
      translation initiation codon for the JEM1 gene. Translation of Jem1p starts from
      the second ATG codon of the previously assumed JEM1 open reading frame, leading
      to the synthesis of a precursor protein of 645 amino acids long. The translated
      Jem1p precursor contains an N-terminal hydrophobic sequence that functions as a
      signal sequence and is removed upon import into the ER lumen. Jem1p is
      peripherally associated with the ER membrane probably through protein-protein
      interactions.

PMID- 9535744
TI  - Expression of CYP2M1, CYP2K1, and CYP3A27 in brain, blood, small intestine, and
      other tissues of rainbow trout.
AB  - Expression of five constitutive forms of cytochrome P450 [(LMC1 (CYP2M1), LMC2
      (CYP2K1), LMC3, LMC4, and LMC5 (CYP3A27)] in selected tissues from sexually
      immature 2-year old female and male rainbow trout (Oncorhynchus mykiss) were
      examined at the translational level by Western blot using polyclonal antibodies
      raised in rabbits against those purified trout hepatic P450s. Tissues examined
      were from brain, liver, muscle, blood, head kidney, trunk kidney, upper
      intestine, stomach, heart, and gonad (ovary or testis). The results showed that
      the liver was the major organ for expression of all the trout P450s studied.
      Trunk kidney was the secondary expression site except for LMC5. Selective
      translational expression of these P450 isoforms or similar proteins was observed
      for LCM1 and LMC5 in brain; for LMC2 and LMC5 in female upper intestine; and for
      LMC2 in blood plasma of the fish studied under the experimental and sampling
      conditions.

PMID- 9535745
TI  - Molecular cloning and characterization of mouse ficolin-A.
AB  - A novel ficolin-related gene was isolated from the mouse liver lambda ZAPII cDNA
      library. The protein encoded by this gene consists of both collagen- and
      fibrinogen-like domains, which are common features of the ficolin family, and was
      named mouse ficolin-A. The amino acid sequence of mouse ficolin-A is 60.2, 59.8,
      59.8, and 59.6% identical to those of porcine ficolin-alpha, -beta, human ficolin
      1, and EBP-37/P35, respectively. Northern blot analysis showed that mRNA of mouse
      ficolin-A is highly expressed in liver and spleen. Immunoblot analysis using an
      anti-mouse ficolin-A antiserum showed that mouse ficolin-A is a plasma protein
      with binding activity to elastin and GlcNAc.

PMID- 9535746
TI  - Up-regulation of glutamate-cysteine ligase gene expression by butylated
      hydroxytoluene is mediated by transcription factor AP-1.
AB  - Several regulatory elements, including AP-1 and NF-kappa B, are present in the
      5'flanking region of the human glutamatex-cysteine ligase (EC 6.3.2.2, gamma
      glutamyl-cysteine synthetase) catalytic subunit (GLCLC) gene. In this study, we
      investigated the role of redox-sensitive transcription factors in the regulation
      of GLCLC gene expression in LLC-PK1 cells that were exposed to the antioxidant
      butylated hydroxytoluene (BHT). Exposure of LLC-PK1 cells to 100 microM BHT
      induced expression of transcription factor AP-1, as demonstrated by an
      electrophoretic mobility shift assay. Peak AP-1 induction occurred after 3 h of
      incubation with BHT, BHT increased luciferase gene expression in cells that were
      transfected with a luciferase reporter vector containing an AP-1 element upstream
      of a SV40 promoter. Northern analysis showed that transcription of GLCLC gene in
      cells after incubation with BHT was increased 30% compared with control cells.
      Cellular glutathione concentrations were also significantly increased in cells
      exposed to BHT. In contrast, exposure of LLC-PK1 cells to 100 microM BHT did not
      alter expression of the transcription factor NF-kappa B. These results show that
      induction of transcription factor AP-1 by BHT is involved in transactivation of
      GLCLC gene expression.

PMID- 9535747
TI  - Unexpected suppression of alpha-smooth muscle actin, the activation marker of
      mesangial cells, by pp60v-src tyrosine kinase.
AB  - Cultured mesangial cells constitutively express alpha-smooth muscle actin (alpha
      SMA), a marker of cellular activation. We unexpectedly found that tyrosine kinase
      pp60v-src, a known activator for a wide range of signalling cascades, suppressed
      the alpha-SMA expression in mesangial cells. The present study was conducted to
      elucidate molecular events involved in this phenomenon. Transfection with a
      reporter plasmid revealed that the serum response element (SRE), the cis-element
      required for alpha-SMA expression, was constitutively active in mesangial cells.
      When mesangial cells were transfected with pp60v-src, activity of both SRE and
      the alpha-SMA promoter was down-regulated. This was associated with depressed
      levels of phosphorylated extracellular signal-regulated kinases (ERKs), but not c
      Jun N-terminal kinase. Selective inhibition of ERKs by PD098059 abrogated
      constitutive SRE activity, leading to suppressed alpha-SMA expression. These
      results uncovered a novel potential of pp60v-src for suppression of alpha-SMA via
      intervention in the ERK-SRE signalling pathway.

PMID- 9535748
TI  - Association between hepatitis B virus core promoter rearrangements and
      hepatocellular carcinoma.
AB  - Hepatitis B virus (HBV) is the major etiological agent of hepatocellular
      carcinoma (HCC). Whether any particular viral variants are associated with HCC is
      unknown. We studied 53 Gambian patients with HCC and 33 HBsAg positive controls.
      A functional part of HBV core promoter and whole precore region were sequenced
      directly and/or after cloning. HBV DNA was amplified from sera from 27 HCC
      patients and in all controls. Fourteen (52%) patients and 12 (36%) controls (NS)
      were found to harbor an HBV strain with G to A transition mutation at position
      1896 leading to HBeAg negative phenotype. Nine (33%) HCC patients and 2 (6%)
      controls (p < 0.01) harbored a mixture of wild type and HBV strains with
      deletions/insertions; strong consensus sequences for topoisomerase I breakage
      were located in the vicinity of these changes. In Africa, HCC is associated with
      HBV strains that have deletions/insertions in the HBV core promoter region.

PMID- 9535749
TI  - Chromosomal localization of a human deoxyribonuclease II gene (DNASE2) to 19p13.2
      p13.1 using both the polymerase chain reaction and fluorescence in situ
      hybridization analysis.
AB  - Recently obtained information on the cDNA encoding human deoxyribonuclease II
      (DNase II) (T. Yasuda et al., 1998, J. Biol. Chem. 273, 2610-2616) has made it
      possible to demonstrate the precise position of the the human DNase II gene
      (DNASE2) on human chromosomes. Two different sets of oligonucleotide primers
      specific for human DNase II cDNA sequences were used to amplify unique DNA
      fragments in the human DNase II gene from a panel of human x rodent hybrid cell
      lines carrying different human chromosomes. Based on this analysis, DNASE2 was
      assigned to human chromosome 19. Furthermore, regional localization of the gene
      to 19p13.2-p13.1 was achieved by fluorescence in situ hybridization analysis
      using a full-length cDNA probe corresponding to the entire open reading frame.

PMID- 9535750
TI  - HIV-1 gp120-induced apoptosis in the rat neocortex involves enhanced expression
      of cyclo-oxygenase type 2 (COX-2).
AB  - The effect of subchronic intracerebroventricular (i.c.v.) injection of the human
      immunodeficiency virus type 1 (HIV-1) recombinant protein gp120 (100 ng, given
      daily for up to 7 consecutive days) on cyclooxygenase type 2 (COX-2) expression
      was studied by immunohistochemistry in the brain of adult rats. In comparison to
      control, bovine serum albumin (100 ng, given i.c.v. for up to 7 days) treated
      animals (n = 6), a single daily injection of the viral protein for 7 consecutive
      days enhanced the number of COX-2 immunoreactive cells in the brain cortex of
      rats (n = 6 per group) and this was accompanied by a 50% increase over control
      PGE2 content in whole brain tissue homogenates (n = 6). In another series of
      experiments, pretreatment of rats (n = 6) with indomethacin (6.0 mg/kg given i.p.
      1 h before gp120 injection), an inhibitor COX activity, prevented apoptotic death
      typically produced by gp120 in the neocortex of rat suggesting that enhancement
      of COX-2 expression may be involved in the mechanisms of apoptosis yielded by the
      HIV-1 coat protein.

PMID- 9535751
TI  - Phospholipase D activity in L1210 cells: a model for oleate-activated
      phospholipase D in intact mammalian cells.
AB  - Phospholipase D (PLD) in lymphocytic mouse leukemic L1210 cells has been found to
      be activated by oleate both in vitro and in intact cells. The PLD activity was
      measured by phosphatidylethanol produced from radiolabeled phosphatidylcholine or
      myristic acid in the presence of ethanol. This oleate-activated PLD was further
      characterized in intact cells and compared with that in HL60 cells. Unlike PLD in
      HL60 cells, the PLD in L1210 cells was activated by unsaturated fatty acids,
      stimulated by melittin, insensitive to guanosine 5'-(3-O-thio)triphosphate (GTP
      gamma S), ADP-ribosylation factor (ARF) and phosphatidylinositol 4,5-bisphosphate
      (PIP2), independent of phorbol 12-myristate 13-acetate (PMA) and staurosporine,
      and inhibited by pervanadate. These observations indicate that the PLD present in
      L1210 cells is distinct from that in HL60 cells. Key PLD properties of L1210
      cells such as insensitivity to GTP gamma S, ARF, PIP2, or PMA were in good
      agreement with currently known in vitro properties of the oleate-activated PLD
      found in mammalian sources. Therefore, the L1210 cells could be used as an intact
      cell source for an oleate-activated PLD.

PMID- 9535752
TI  - Expression of the rat adrenomedullin receptor or a putative human adrenomedullin
      receptor does not correlate with adrenomedullin binding or functional response.
AB  - There has been considerable difficulty in defining distinct adrenomedullin (AM)
      binding sites and function in vivo. However, a rat adrenomedullin receptor (rAMR)
      and a putative human adrenomedullin receptor (hAMR) have recently been reported.
      We attempted to confirm and extend the pharmacological characterization of these
      cloned receptors. COS-7 cells transfected with rAMR or epitope tagged rAMR
      display abundant rAMR mRNA expression and cell-surface receptor localization.
      Specific 125I-AM binding is detected in transfected cells; however, similar
      levels of binding are also detected in cells transfected with vector DNA alone.
      This AM binding site fails to mediate any changes in cAMP in response to AM. In
      contrast, Swiss 3T3 cells, expressing specific endogenous AM receptors, display
      AM binding and functional cAMP responses. Transfection studies performed with the
      putative hAMR yield similar results. These data suggest that the proposed rAMR
      and hAMR do not represent authentic adrenomedullin receptors.

PMID- 9535753
TI  - Characteristics analysis of the luzA gene encoding chaperone from Photobacterium
      leiognathi related to bioluminescence.
AB  - Nucleotide sequence of the luzA gene (GenBank accession No. AF039303) from
      Photobacterium leiognathi ATCC 25521 (NCIMB 2193) has been determined, and the
      chaperone encoded by the luzA gene was deduced. The LuzA chaperone has a
      calculated M(r) 26,295 and comprises 230 amino acid residues; the hydrophobic
      alpha-helix N-terminal 21 amino acid residues MKKTIFALLFMSVFI SYPSFA is the
      leader peptide, therefore the matured LuzA chaperone has a calculated M(r) 23,871
      and comprises 209 amino acid residues only. The periplasmic LuzA chaperone is the
      protein concerned with the protein folding, assembly and stability. The luzA gene
      and the related genes are closely linked to the sod gene, that encoding Cu/Zn
      superoxide dismutase enables to enhance bioluminescence of the lux operon; the
      gene order of the luzA gene and related genes is -ufo'-luzA-ufoI-ufoII-ter->-R&R'
      sod-ufo-- >. In trans complementation bioluminoassays in vivo elicit that the
      LuzA chaperone might be not directly concerned with bioluminescence of the lux
      operon from P. leiognathi in E. coli, but might enable to stabilize the proteins
      related to bioluminescence. The unidentified ufoII gene closely linked to the
      luzA gene is able to enhance bioluminescence.

PMID- 9535754
TI  - Synergistic effect of cyclic AMP and insulin on the expression of cyclin A gene
      in Swiss 3T3 cells.
AB  - Cyclic AMP and insulin exert a synergistic mitogenic effect on Swiss 3T3 cells.
      Here, we showed that the activity of cyclin A-dependent kinase was elevated 3
      fold at 24 h after cotreatment of cells with dibutyryl cAMP and insulin. The
      cotreatment elevated cyclin A protein levels 12-fold higher than those of insulin
      treated cells without altering the levels of CDK2 and p27Kip1 proteins.
      Interestingly, the half-life of cyclin A protein increased from 7 h in the
      insulin-treated cells to 22 h in the cotreated cells. Levels of cyclin A mRNA
      were also elevated 9-fold. Cotreatment synergistically increased the binding
      activities of transcription factors to the NF-Y and the E2F-like sites of the
      cyclin A promoter. However, neither NF-Y nor E2F was involved in the binding.
      These results suggest that the synergistic elevation of cyclin A protein may be
      achieved by both the stabilization of cyclin A protein and the recruitment of
      transcription factors to the NF-Y and E2F-like sites of the cyclin A promoter.

PMID- 9535755
TI  - Molecular cloning and expression analysis of GFR alpha-3, a novel cDNA related to
      GDNFR alpha and NTNR alpha.
AB  - Glial-cell-line-derived neurotrophic factor (GDNF) and neurturin (NTN) are
      structurally related to TGF-beta and are survival factors for sympathetic,
      sensory, and central nervous system neurons. GDNF transmits its signal primarily
      through a receptor complex containing the receptor tyrosine kinase Ret and a
      glycosyl-phosphatidylinositol (GPI)-linked receptor, GDNFR alpha. NTN utilizes a
      receptor complex system that consists of Ret and another GPI-linked receptor,
      NTNR alpha. We have identified a mouse cDNA, termed GFR alpha-3, that encodes a
      putative GPI-linked receptor. At the protein level, mouse GFR alpha-3 is 35%
      identical to mouse GDNFR alpha and 36% identical to mouse NTNR alpha. Northern
      blot analysis showed that GFR alpha-3 is expressed in fetal mouse heart, brain,
      lung, and kidney and adult heart. These results indicate that the tissue
      distribution of GFR alpha-3 mRNA is different from that of GDNFR alpha or NTNR
      alpha mRNA, and suggest that GFR alpha-3 may function in differentiation of
      embryonic cells expressing its mRNA.

PMID- 9535756
TI  - Isolation and characterization of the Xanthomonas campestris rpoH gene coding for
      a 32-kDa heat shock sigma factor.
AB  - Degenerate oligonucleotide primers corresponding to the conserved regions of
      bacterial heat shock sigma factor RpoH (sigma 32) were used to amplify a 190-bp
      fragment by PCR on the X. campestris pv. campestris strain 11 chromosome. Using
      this fragment as a probe, plasmid pXC57 carrying a 4.7-kb insert was isolated
      from a genomic library of Xc11. Sequence analysis of a stretch of 2,053 bp from
      the pXC57 insert revealed an ORF encoding a polypeptide of 291 aa (32,854 dal)
      which displays 59.6% and 57.3% identity to the rpoH gene products of E. coli and
      P. aeruginosa, respectively. The Xc11 rpoH gene was able to complement the RpoH
      deficient E. coli strain A7448. Both amino acid and mRNA sequences deduced from
      the Xc11 rpoH gene show structural features characteristics of the corresponding
      sequences from those of the gamma subgroup proteobacteria. The RpoH levels in
      Xc11 were demonstrated to increase transiently in response to heat shock
      treatment by immunoblot analysis using the polyclonal antibody raised against the
      purified Xc11 RpoH.

PMID- 9535757
TI  - Inhibition of pea chloroplast DNA helicase unwinding and ATPase activities by DNA
      interacting ligands.
AB  - DNA helicases unwind the duplex DNA in an ATP dependent manner and thus play an
      essential role in DNA replication, repair, recombination and transcription. Any
      DNA-interacting ligand which will modulate DNA helicase activity may interrupt
      practically all kinds of DNA transactions. There are no studies on the effect of
      various cytotoxic DNA-interacting ligands on organelle helicases. We have
      determined the effect of camptothecin, VP-16 (etoposide), ellipticine, genistein,
      novobiocin, m-AMSA, actinomycin C1, ethidium bromide, daunorubicin and
      nogalamycin on unwinding and ATPase activities of purified chloroplast DNA
      helicase from pea (Pisum sativum). Our study has shown that DNA-intercalating
      ligands actinomycin C1, ethidium bromide, daunorubicin and nogalamycin were
      inhibiting the DNA unwinding activity with an apparent Ki of 2.9 microM, 3.0
      microM, 1.4 microM and 1.0 microM, respectively. These four inhibitors also
      inhibited the ATPase activity of pea chloroplast DNA helicase. These results
      indicate that the intercalation of the inhibitors into DNA generates a complex
      that impedes the translocation of chloroplast DNA helicase, resulting in both
      inhibition of unwinding activity and ATP hydrolysis. This study would be useful
      for understanding the mechanism of organelle DNA helicase unwinding and the
      mechanism by which these DNA-interacting ligands inhibit cellular function.

PMID- 9535759
TI  - Inhibition of GPI phospholipase C from Trypanosoma brucei by fluoro-inositol
      dodecylphosphonates.
AB  - Glycosyl phosphatidylinositol phospholipase C (GPI-PLC) of Trypanosoma brucei is
      inhibited by myo-inositol(Ins)-1-O-dodecylphosphonate (VP-602L). Several novel
      fluoro-substituted analogs of 2-deoxy-myo-Ins-1-O-dedecylphosphonate, among which
      2-deoxy-2-fluoro-scyllo-Ins-1-O-dodecylphosphonate (VP-616L) was the most
      powerful, were shown to be competitive inhibitors of GPI-PLC. VP-616L was 14-fold
      more active than VP-602L. 2-Deoxy-2-fluoro-myo-Ins-1-O-dodecylphosphonate and 2
      deoxy-2,2-difluoro-myo-Ins-1-O-dodecylphosphonate were 1.55- and 4.67-fold,
      respectively, more potent than VP-602L. Methyl 2-deoxy-2,2-difluoro-myo-Ins-1-O
      dodecylphosphonate did not inhibit GPI-PLC. These observations provide several
      insights into how GPI-PLC might interact with its substrate at the active site.
      We surmise that (i) the 2-OH of Ins is probably dispensable for substrate
      recognition; (ii) an equatorially oriented active site residue might interact
      with substituents at the 2-position of Ins, and (iii) the negative charge on the
      phosphoryl at the 1-OH position of Ins might be important for substrate
      recognition.

PMID- 9535758
TI  - Induction of CYP102 (cytochrome P450BM-3) in Bacillus megaterium by 17 beta
      estradiol and 4-sec-butylphenol.
AB  - CYP102 (Cytochrome P450BM-3) is induced in Bacillus megaterium by barbiturates,
      peroxisome proliferators, and nonsteroidal anti-inflammatory drugs. We now
      describe the induction of CYP102 in B. megaterium by 17 beta-estradiol and by 4
      sec-butylphenol. These estrogens interact with the repressor protein Bm3R1,
      causing it to dissociate with the operator of the CYP102 gene and allowing
      transcription to occur. We have developed a stable transfection of a construct
      into B. megaterium of a truncated CYP102 gene coupled with the luciferase gene in
      a promoterless plasmid and have used this construct to test the induction of
      CYP102 by these estrogens. Estradiol demonstrated a dose-dependent induction of
      CYP102 which saturated at a 2-fold increase at 150 microM 4 hr post-addition. 4
      sec-Butylphenol produced a dose-dependent and time-dependent induction up to 300
      microM and 6 hr post-induction.

PMID- 9535760
TI  - Evidence that two reports of mtDNA cytochrome c oxidase "mutations" in
      Alzheimer's disease are based on nDNA pseudogenes of recent evolutionary origin.
AB  - Recently, two reports [R. E. Davis et al. (1997) Proc. Natl. Acad. Sci. USA 94,
      4564-4569 and E. Fahy et al. (1997) Nucleic Acids Res. 25, 3102-3109] described a
      series of heteroplasmic mitochondrial DNA (mtDNA) mutations in the genes encoding
      two cytochrome c oxidase subunits (CO1 and CO2) which segregated in higher
      abundance with Alzheimer's disease subjects than controls. Using mtDNA-depleted
      NT2 cells, we provide further evidence that these two reports are erroneously
      based on a PCR artifact arising from the amplification of nuclear DNA encoded
      mtDNA pseudogenes (mtDNA psi s). Our findings are similar, but not identical, to
      other recent studies of these putative mtDNA psi sequences. This sequence
      variability may indicate that multiple mtDNA psi s, all of comparatively recent
      evolutionary origin are involved. While such pseudogenes are interesting in that
      they provide a molecular evolutionary "snapshot" of human ancestral mtDNA, it is
      unlikely that they play any role in the etiology of Alzheimer's disease.

PMID- 9535761
TI  - Comparison of the conformational state and in vitro refolding of yeast chaperonin
      protein cpn10 with bacterial GroES.
AB  - Gel filtration studies demonstrate that the heptameric complex of yeast cpn10 (pI
      around 8.8) reversibly disassembles into monomers when lowering the pH to 4.5,
      whereas its secondary structure is retained as demonstrated by circular
      dichroism. Monomeric yeast cpn10 does not bind to GroEL in the presence of
      nucleotides, whereas under identical conditions E. coli cpn10 (GroES), having a
      strong sequence homology to the yeast form but a pI of 5.2, shows no pH-dependent
      dissociation and is able to complex with GroEL at both pH 7.5 and 4.5. Using
      circular dichroism it is shown that, unlike E. coli cpn10, yeast cpn10 is not
      able to refold spontaneously after first being fully unfolded in 8 M urea.
      However, refolding of yeast cpn10 to a complex that can be recognised by GroEL
      depends on the presence of a lipid-water interface with a specificity for
      negatively charged lipids. We suggest that the requirements for refolding of
      yeast cpn10 are related to its post-translational transport and subcellular
      localization.

PMID- 9535762
TI  - Papain catalysed hydantoin hydrolysis in the synthesis of amino acids.
AB  - Papain has been shown, for the first time, to exhibit hydantoinase activity. It
      hydrolyzes the 5-mono and 5,5'-disubstituted hydantoins with linear and cyclic
      substituents, with a higher activity for the latter, to the corresponding N
      carbamoyl amino acids, which on chemical hydrolysis yield the corresponding amino
      acids. The up-scaling of this simple procedure could be a major break-through for
      amino acid synthesis in chemical and pharmaceutical industries.

PMID- 9535763
TI  - Cloning and expression of an acyl-CoA dehydrogenase from Mycobacterium
      tuberculosis.
AB  - A gene from Mycobacterium tuberculosis coding for acyl-CoA dehydrogenase was
      cloned, overexpressed and characterized on the basis of enzyme activity with
      various chain length substrates. The results show that the protein is a medium
      chain acyl-CoA dehydrogenase (MCADH). The mycobacterium protein expressed appears
      to be unique, since by comparison, the active site glutamic acid of the protein
      does not lie in the same position as other well characterized MCADH, but in a
      position present in long chain and isovaleryl acyl-CoA dehydrogenases (LCADH and
      IVDH).

PMID- 9535764
TI  - Subunit swapping in the Mex-extrusion pumps in Pseudomonas aeruginosa.
AB  - Pseudomonas aeruginosa encodes three sets of antibiotic extrusion proteins
      designated as MexA,B.OprM, MexC,D-OprJ and MexE,F-OprN regulated by the nalB,
      nfxB and nfxC genes, respectively. MexB,D,F, OprM, J,N and MexA,C,E function as
      the inner membrane pumps, the outer membrane channels and the membrane fusion
      proteins, respectively. To investigate the possibility of subunit
      interchangeability, we constructed the following combinations of chimeric pumps:
      MexA,D-OprM/delta MexB, MexC,B-OprM/delta MexA, and MexA,B-OprJ/delta OprM. The
      strains producing MexA,D-OprM/delta MexB and MexC,B-OprM/delta MexA failed to
      restore the antibiotic resistance shown in the strains producing the natural
      combinations of the subunit proteins. These results suggested that the inner
      membrane components cannot be interchanged. In contrast, the stains producing
      MexA,B-OprJ/delta OprM exhibited higher resistance to several antibiotics than
      the mutant lacking OprM and lower resistance than the strain overexpressing OprM.
      This result suggests that OprJ may complement the OprM function partially. A
      spectrum of antibiotics, of which the minimum inhibitory concentrations were
      restored partially by the complementation, was the same as the spectrum to which
      the nalB type mutant shows resistance. We surmised from these results that the
      MexA/MexB unit sustains the substrate specificity of the MexA,B-OprM machinery.

PMID- 9535765
TI  - Protective role of black tea against oxidative damage of human red blood cells.
AB  - The purpose of our study was to explore the possible scavenging property of black
      tea and catechins, the major flavonols of tea-leaf, against damage by oxidative
      stress. For this purpose, human red blood cell (rbc) was taken as the model and
      the oxidative damage was induced by a variety of inducers, e.g. phenylhydrazine
      (PHX), Cu(2+)-ascorbic acid, and xanthine/xanthine oxidase systems. Lipid
      peroxidation of pure erythrocyte membrane and of whole red blood cell could be
      completely prevented by black tea extract. Similarly, black tea provided total
      protection against degradation of membrane proteins. Finally, membrane fluidity
      studies as monitored by the fluorescent probe 1,6 diphenyl hexa 1,3,5-triene
      (DPH) showed considerable disorganization of its architecture that could be
      restored back to normal on addition of black tea or free catechins. Black tea
      extract in comparison to free catechins seemed to be a better protecting agent
      against various types of oxidative stress. Apparently, conversion of catechins to
      partially polymerized products such as theaflavin or thearubigin during
      'fermentation' process for making black tea has no deleterious effect on its
      scavenging properties.

PMID- 9535766
TI  - Conserved enzyme-substrate electrostatic attraction in prokaryotic Cu,Zn
      superoxide dismutases.
AB  - The catalytic activity of wild type Escherichia coli Cu,Zn superoxide dismutases
      and of two mutants in which two lysine residues conserved in most bacterial Cu,Zn
      superoxide dismutases have been replaced by serine was investigated by pulse
      radiolysis and Brownian dynamics simulations. Experimental and computational data
      show that neutralization of Lys60 strongly reduces the catalytic activity of the
      enzyme (approximately 50%), indicating that this residue has a primary role in
      the electrostatic attraction of the substrate towards the catalytic copper.
      Neutralization of Lys63 does not significantly influence the catalytic rate
      constant. The results suggest that prokaryotic Cu,Zn superoxide dismutases have
      evolved an electrostatic mechanism to facilitate the enzyme-substrate encounter
      that is functionally equivalent to that already found in the eukaryotic enzymes.

PMID- 9535767
TI  - Growth properties and growth factor responsiveness in skin fibroblasts from
      centenarians.
AB  - Human fibroblast cultures, which have a finite replicative lifespan in vitro, are
      the most widely used model for the study of senescence at the cellular level. An
      inverse relationship between replicative capability and donor age has been
      reported in human fibroblast strains. We studied the growth capacity of
      fibroblast primary cultures derived from people whose lifespan was as closer as
      possible to the expected maximum human lifespan, i.e. people over one hundred.
      Our data suggest that outgrowth of fibroblasts from biopsies, growth kinetics at
      different population doubling levels, capability to respond to a classical
      mitogenic stimulus (such as 20% serum) and a variety of growth factors, were
      remarkably similar in fibroblasts from centenarians and young controls. On the
      whole, our data challenge the tenet of a simple and strict relationship between
      in vivo aging and in vitro proliferative capability of human fibroblasts, at
      least at the individual level.

PMID- 9535768
TI  - Differential induction of NAD(P)H:quinone oxidoreductase by anti-carcinogenic
      organosulfides from garlic.
AB  - This study was undertaken to elucidate the mechanism of organ specificity and
      differential efficacy of garlic organosulfides (OSCs) [diallyl sulfide (DAS),
      diallyl disulfide (DADS), diallyl trisulfide (DATS), dipropyl sulfide (DPS) and
      dipropyl disulfide (DPDS)] in preventing benzo(a)pyrene (BP)-induced
      tumorigenesis in mice. The results of the present study reveal a good correlation
      between chemopreventive efficacies of garlic OSCs and their inductive effects on
      the expression of NAD(P)H:quinone oxidoreductase (NQO), an enzyme implicated in
      the detoxification of activated quinone metabolites of BP. Treatment of mice with
      DADS and DATS, which are potent inhibitors of BP-induced forestomach
      tumorigenesis, resulted in a statistically significant increase (2.4- and 1.5
      fold, respectively) in forestomach NQO activity. In addition, DADS and DATS were
      much more potent inducers of forestomach NQO activity than DAS, which is a weak
      inhibitor of BP-induced forestomach tumorigenesis than the former compounds.
      Propyl-group containing OSCs (DPS and DPDS), which do not inhibit BP-induced
      tumorigenesis, did not affect forestomach NQO activity. Similar to forestomach, a
      good correlation was also observed between effects of these OSCs against BP
      induced pulmonary tumorigenesis and their effects on NQO expression in the lung.
      For example, treatment of mice with DAS, which is a potent inhibitor of BP
      induced pulmonary tumorigenesis, resulted in about 3.2-fold increase in pulmonary
      NQO activity. On the other hand, this activity was increased by about 1.5-fold
      upon DATS administration, which does not inhibit BP-induced cancer of the lung.
      In conclusion, our results suggest that induction of NQO may be important in anti
      cancer effects of garlic OSCs.

PMID- 9535769
TI  - Glycogen storage disease type II: identification of four novel missense mutations
      (D645N, G648S, R672W, R672Q) and two insertions/deletions in the acid alpha
      glucosidase locus of patients of differing phenotype.
AB  - Glycogen storage disease type II (GSDII), an autosomal recessive myopathic
      disorder, results from deficiency of lysosomal acid alpha-glucosidase. We
      searched for mutations in an evolutionarily conserved region in 54 patients of
      differing phenotype. Four novel mutations (D645N, G448S, R672W, and R672Q) and a
      previously described mutation (C647W) were identified in five patients and their
      deleterious effect on enzyme expression demonstrated in vitro. Two novel frame
      shifting insertions/deletions (delta nt766-785/insC and +insG@nt2243) were
      identified in two patients with exon 14 mutations. The remaining three patients
      were either homozygous for their mutations (D645N/D645 and C647W/C647W) or
      carried a previously described leaky splice site mutation (IVS1-13T-->G). For all
      patients "in vivo" enzyme activity was consistent with clinical phenotype.
      Agreement of genotype with phenotype and in vitro versus in vivo enzyme was seen
      in three patients (two infantile patients carrying C647W/C647W and
      D645N/+insG@nt2243 and an adult patient heteroallelic for G648S/IVS1-13T-->G).
      Relative discordance was found in a juvenile patient homozygous for the non
      expressing R672Q and an adult patient heterozygous for the minimally expressing
      R672W and delta nt766-785/+insC. Possible explanations include differences in in
      vitro assays vs in vivo enzyme activity, tissue specific expression with
      diminished enzyme expression/stability in fibroblasts vs muscle, somatic
      mosaicism, and modifying genes.

PMID- 9535770
TI  - AMP activation of snake muscle fructose 1,6-bisphosphatase at alkaline pH.
AB  - AMP, an allosteric inhibitor at neutral pH, activates snakes muscle fructose 1,6
      bisphosphatase at pH 9.2. The activation is virtually unique for the snake muscle
      enzyme: activation was not observed for the enzymes from either human and rabbit
      liver or porcine kidney. The activation is Mg(2+)-dependent but was not observed
      until the concentration of Mg2+ reaches 1 mM. It is known that subtilisin,
      trypsin, or lysosomal proteases hydrolyse the N-terminal loop of fructose-1,6
      bisphosphatase in the vicinity of amino acid residue 60 generating a form of the
      enzyme with a pH optimum at 9.2. In the presence of AMP, the pH profile of the
      native snake muscle enzyme resembles that of the alkaline form and modification
      of the highly reactive sulfhydryl group abolishes AMP activation. The fact that
      AMP has a dual function at different pH levels suggests that pH might be an
      important factor in regulating the activity of the enzyme upon binding of AMP at
      the allosteric site. Indeed, the mode of AMP binding to the allosteric site may
      differ at neutral and alkaline pH levels. A residue that ionizes with a pKa of
      8.9 might be involved in this process.

PMID- 9535771
TI  - Order of fusions between bacterial and mammalian proteins can determine
      solubility in Escherichia coli.
AB  - We made fusions between Escherichia coli maltose-binding protein (MBP) and the
      mammalian aspartic proteinases pepsinogen or procathepsin D. When MBP was at the
      N-terminus, the fusions were soluble in E. coli. When the order was reversed, the
      chimeric proteins formed inclusion bodies. The data suggest that the solubility
      of fusion proteins is controlled by whether the protein domains emerging first
      from the ribosome normally fold into soluble or insoluble states. The soluble MBP
      aspartic proteinase fusions were stable but proteolytically inactive. MBP
      pepsinogen, however, was efficiently renatured from 8 M urea in vitro, suggesting
      that the E. coli cytoplasm does not support folding of the mammalian partner
      protein to the native state. Thus, inclusion body formation may be the
      consequence, rather than the cause, of non-native folding in vivo, and in E. coli
      soluble proteins may fold into states different from those reached in vitro.

PMID- 9535773
TI  - Cellular responses to DNA damage in the absence of Poly(ADP-ribose) polymerase.
AB  - Poly(ADP-ribose) polymerase (PARP) is a nuclear enzyme which is catalytically
      activated by DNA strand interruptions. The involvement of PARP has been
      implicated in different cellular responses to genotoxic damage, including cell
      survival, DNA repair, transformation, and cell death. However, the exact
      contribution of PARP polypeptide or its enzymatic product has remained ill
      defined. Recent studies with two different PARP knock out mice have demonstrated
      the beneficial role of PARP in maintaining genomic integrity and in survival
      responses after exposure to whole body gamma-irradiation. Other studies have
      demonstrated the instrumental role of PARP in death of the neuronal cells after
      ischemia-reperfusion injury. The recombination inhibiting function of PARP at DNA
      strand breaks was more evident in a model system deficient in activities of two
      major DNA strand break binding proteins, PARP and DNA-dependent protein kinase.
      The present review summarizes similarities and differences obtained with the two
      PARP knock out mice and reanalyzes the role of PARP in various cellular responses
      to DNA damage.

PMID- 9535774
TI  - Generation of nitric oxide from streptozotocin (STZ) in the presence of
      copper(II) plus ascorbate: implication for the development of STZ-induced
      diabetes.
AB  - Streptozotocin (STZ) is widely used as a strong inducer of insulin-dependent
      diabetes in experimental animals. Although nitric oxide (NO) generation from STZ
      has been proposed to be responsible for the toxicity of pancreatic B-cells, the
      mechanism is yet unknown. We found that STZ generates NO in the presence of
      Cu(II) plus ascorbate. In addition, nicotinamide, which is an antidiabetic agent
      against STZ, has been found to inhibit NO generation from STZ during the reaction
      with Cu(II) plus ascorbate. Since rat pancreatic islets contain both ascorbate
      and Cu at the concentrations of 3.5 mM and 1. 0 nmol/mg protein, respectively,
      our present results indicate that (1>) NO generation is responsible for the
      development of STZ-induced diabetes and (2) mechanism for the protection of
      diabetes by nicotinamide is due to the inhibition of NO generation from STZ
      through complex formation between nicotinamide and Cu (I), which is reduced by
      ascorbate.

PMID- 9535775
TI  - Free radical stimulation of tyrosine kinase and phosphatase activity in human
      peripheral blood mononuclear cells.
AB  - Human lymphocytes were challenged with reactive oxygen species (ROS) generated by
      xanthine/xanthine oxidase leading to an increase in tyrosine phosphorylation,
      together with an increase in tyrosine phosphatase activity. In the presence of 50
      microM vanadate and xanthine/xanthine oxidase, tyrosine phosphatase activity was
      inhibited and a marked increase in tyrosine phosphorylation was observed. The
      addition of catalase abolished the increase in tyrosine phosphorylation while the
      addition of superoxide dismutase had no effect. This suggests that vanadate
      together with hydrogen peroxide derived from xanthine/xanthine oxidase activity,
      interact to produce an agent that is an effective inhibitor of tyrosine
      phosphatase activity. When human lymphocytes were challenged with
      xanthine/xanthine oxidase in the presence of 50 microM CuCl2, an increase in both
      tyrosine phosphatase and kinase activity was observed. Cupric ions inhibited
      xanthine oxidase activity by 84%; neither superoxide or hydroxyl radicals could
      be detected, but traces of hydrogen peroxide were detected in the medium. We
      conclude that unbound metals can interact with ROS and readily influence
      signalling mechanisms in human lymphocytes.

PMID- 9535776
TI  - Glycosylation of the tandem repeat unit of the MUC2 polypeptide leading to the
      synthesis of the Tn antigen.
AB  - A synthetic peptide corresponding to the human MUC2 tandem repeat domain
      containing 14 Thr residues was glycosylated in vitro using UDP-GalNAc and
      microsomal membranes of the colorectal cancer cell line, LS180. The products were
      fractionated by reverse phase HPLC, which gave seven glycopeptide fractions.
      Their molecular weights were estimated by matrix-assisted laser
      desorption/ionization mass spectrometry, the values obtained corresponding to
      glycopeptides containing from one to ten GalNAc residues. On solid phase
      radioimmunoassaying involving a monoclonal anti-Tn antibody (MLS128), it was
      found that the glycopeptides containing nine or ten GalNAc residues were strongly
      immunoreactive, whereas the glycopeptides containing less than six GalNAc
      residues were inactive, indicating that a cluster of GalNAc-Thr is essential for
      the Tn antigenicity.

PMID- 9535777
TI  - Modification at C6 of the terminal galactosyl residues of cobra venom factor
      abolishes anti-alpha-Gal antibody immunoreactivity without affecting functional
      activity.
AB  - The N-linked oligosaccharides of cobra venom factor (CVF) contain unique terminal
      alpha-galactosylated Lewis X structures. We have previously shown that CVF
      immobilized on nylon membranes binds naturally occurring human anti-alpha-Gal
      antibody. The present study shows that soluble CVF can effectively inhibit the
      binding of anti-alpha-Gal antibody to CVF-coated microtiter plates, indicating
      that the terminal alpha-galactosyl residues of the functionally active CVF are
      accessible to anti-alpha-Gal antibody binding. Modification of the terminal
      galactosyl residues of CVF by treatment with galactose oxidase and in situ
      derivatization of the generated aldehyde groups with hydrazides abolished the
      human anti-alpha-Gal antibody immunoreactivity without affecting the complement
      activating activity.

PMID- 9535778
TI  - Lipopolysaccharide activates endothelial nitric oxide synthase through protein
      tyrosine kinase.
AB  - Vascular endothelial cell injury or activation by lipopolysaccharide (LPS) plays
      an important role in the pathogenesis of endotoxin shock. However, the effect of
      LPS on NO production from vascular endothelial cells (ECs) is incompletely
      understood. In this study, bovine coronary venular ECs were treated with LPS and
      the release of NO and expression of the endothelial NO synthase (ecNOS) were
      examined. We found that the ecNOS activity is transiently enhanced by LPS within
      the time scale of about 10 h due to the interplay between two LPS-induced
      mechanisms. Within the first 10 h of LPS treatment, the specific activity of
      ecNOS is increased by a post-translational modification mediated through a
      protein tyrosine kinase cascade. After about 10 h of treatment, however, LPS
      destabilizes the transcript of ecNOS and thus decreased the expression level and
      total activity.

PMID- 9535779
TI  - A novel disorder of N-glycosylation due to phosphomannose isomerase deficiency.
AB  - Three siblings suffered from an unusual disorder of cyclic vomiting and
      congenital hepatic fibrosis. Serum transferrin isoelectric focusing showed
      increased asialo- and disialotransferrin isoforms as seen in the carbohydrate
      deficient glycoprotein (CDG) syndrome type I. Phosphomannomutase, which is
      deficient in most patients with type I CDG syndrome, was found to be normal in
      all three patients. Structural analysis of serum transferrin revealed
      nonglycosylated, hypoglycosylated, and normoglycosylated transferrin molecules.
      These findings suggested a defect in the early glycosylation pathway.
      Phosphomannose isomerase was found to be deficient and the defect was present in
      leucocytes, fibroblasts, and liver tissue. Phosphomannose isomerase deficiency
      appears to be a novel glycosylation disorder, which is biochemically
      indistinguishable from CDG syndrome type I. However, the clinical presentation is
      entirely different.

PMID- 9535780
TI  - alpha-Mannosidase from Trichoderma reesei participates in the postsecretory
      deglycosylation of glycoproteins.
AB  - The 160 kDa alpha-mannosidase (E.C. 3.2.1.24) isolated from culture filtrate of
      Trichoderma reesei has wide aglycon specificity but cleaves the alpha1 --> 2 and
      alpha1 --> 3 mannosidic bonds with higher rate than alpha1 --> 6 bond and slowly
      hydrolyses yeast mannan and 1,6-alpha-mannan. The specific activity of the enzyme
      and rate constant in the reaction with p-nitrophenyl-alpha-D-mannopyranoside were
      0.15 U/mg and 1.62 x 10(-4) microM/min/microg, respectively, at optimal pH 6.5.
      We have found that in vitro enzyme is able to cleave off 30% of total alpha
      mannopyranosyl residues from N- and O-linked glycans of secreted glycoproteins.
      The activity of the alpha-mannosidase toward glycoproteins in vivo was studied
      comparing the structures of O- and N-linked glycans of glycoproteins isolated
      from the cultures growing with and without 1-deoxymannojirimycin, an inhibitor of
      alpha-mannosidases. Difference in structures of these glycans may be explained by
      postsecretory deglycosylation catalysed by the alpha-mannosidase.

PMID- 9535781
TI  - Upregulation of functional ryanodine receptors during in vitro aging of human
      diploid fibroblasts.
AB  - We demonstrate for the first time that cellular aging in vitro is accompanied by
      a dramatic elevation in the levels of ryanodine receptor-bearing Ca2+ channels.
      These channels normally reside within microsomal membranes and gate Ca2+ release
      from intracellular stores. We therefore measured cytosolic Ca2+ levels in 'young'
      (30 mean population doublings, MPDs) and 'senescent' (53 to 58 MPDs) human
      diploid fibroblasts (HDFs). Application of the known ryanodine receptor
      modulators, caffeine or cyclic adenosine diphosphate-ribose (cADPr), triggered
      cytosolic Ca2+ signals in both young and senescent cells. The signal magnitude
      however was significantly greater in senescent compared with young HDFs. In
      parallel, incubation with a highly specific anti-ryanodine receptor antiserum
      resulted in specific immunofluorescence only in senescent HDFs. We envisage that
      elevated levels of functional ryanodine receptors may underlie the defective Ca2+
      handling and cellular degeneration that occurs with aging.

PMID- 9535782
TI  - Protonation of the neutral repeats of the RNA polymerase II CTD.
AB  - The CTD (carboxy-terminal repeat domain) of the largest subunit of RNA Polymerase
      II in most eukaryotes consists of from 26 to 52 seven amino acid repeats, the
      consensus sequence of which is YSPTSPS. Even though this consensus repeat does
      not contain residues that are normally protonated under the conditions used for
      positive ion electrospray mass spectrometry, we find that the CTD acquires about
      one proton per repeat when analyzed by this procedure. We have termed this
      phenomenon superprotonation. Superprotonation is apparently a property of the
      consensus sequence as the repeat peptide, (YSPTSPS)4, is superprotonated whereas
      other proteins and the repeat peptides (YSPTSPK)4, (YSPTSPR)4 and (YSPTAPR)4 are
      not. The highly conserved nature of the contiguous consensus repeats in organisms
      ranging from yeast to mammals implies that the functionally significant behavior
      of the domain is easily perturbed. We propose that CTD superprotonation is a
      manifestation of a unique biophysical property that will influence and could be
      the basis for consensus repeat function in vivo.

PMID- 9535783
TI  - An E-box sequence acts as a transcriptional activator for BC1 RNA expression by
      RNA polymerase III in the brain.
AB  - BC1 RNA is a small cytoplasmic RNA that is transcribed by RNA polymerase III (Pol
      III) in the rodent nervous system. In addition to essential intragenic promoter
      elements for Pol III, the BC1 RNA gene has five E-box sequences (CANNTG) in its
      5' flanking region. Deletion analysis using an in vitro transcription system
      revealed that the region containing the E2 site (CAATTG) was necessary for
      effective transcription of BC1 RNA. A construct with point mutations within the
      E2 site showed reduced transcriptional activity. Furthermore, DNaseT I protection
      and gel retardation assays demonstrated that the E2 site was recognized
      specifically by a brain nuclear protein(s). These results suggest that the
      upstream E-box sequence and its binding protein may be involved in the regulation
      by Pol III of preferential BC1 RNA expression in the brain.

PMID- 9535784
TI  - Striking evolutionary conservation of a cis-element related to nuclear receptor
      target sites and present in TR2 orphan receptor genes.
AB  - A systematic scanning of nucleic acid databases for DNA elements made of
      combinations of RGGTCA nuclear receptor half sites, has revealed that identical
      19 nucleotide-long motifs composed of two inverted RGGTCA sites with a spacing of
      7 nucleotides (IR7), are present upstream of the regions coding for the human TR2
      and of the sea urchin SpSHR2 orphan receptors. We have developed an experimental
      strategy based on PCR, to check if this IR7 could correspond to an unusually long
      cis-element, conserved along evolution and regulating the TR2 genes. We found
      that indeed IR7 is present in the 5' untranslated region of TR2 genes from all
      species tested, including Xenopus, rainbow trout, zebrafish and mouse. The exact
      conservation throughout the animal kingdom of such a long, non repetitive and non
      coding genomic region, highly suggests that it should ensure important biological
      functions. In addition, this work has allowed the identification of a new, non
      coding, upstream exon in the mouse TR2 gene present in testicular TR2 mRNAs.

PMID- 9535785
TI  - Regulation of cyclin D-dependent kinase activity in rat liver regeneration.
AB  - The regulation of cyclin D-dependent kinase activity in tissue regeneration in
      vivo has not been fully described. In young adult rat liver after 70% partial
      hepatectomy, the association of cyclin D1 with cdk4 was significantly promoted
      during G1 phase and was maximal at 18 hr, corresponding mainly to late G1. Cyclin
      D1-dependent kinase activity also strongly increased during G1 phase. The timing
      of the induction of cyclin D1 / cdk4 complex assembly correlated well with that
      of cyclin D1-dependent kinase activity. At 18 hr after partial hepatectomy, the
      amounts of CDK inhibitors p21(CIP1) and p27(KIP1) were also maximal, while only
      one-tenth of p21(CIP1) and of p27(KIP1) was associated with cyclin D1. These
      findings suggest that cyclin D1, cdk4 and their association act as promoting
      factors, and that both p21(CIP1) and p27(KIP1) may have physiological functions
      as adaptor proteins in additions to their roles as CDK inhibitors in rat liver
      regeneration.

PMID- 9535786
TI  - Decreased BRCA1 expression levels may arrest the cell cycle through activation of
      p53 checkpoint in human sporadic breast tumors.
AB  - Predisposition to breast cancer has been attributed to mutant BRCA1 alleles
      whereas no BRCA1 mutation has been described yet in sporadic breast tumours. As
      an initial characterization of the regulation and function of the BRCA1 gene in
      sporadic breast cancer, we have compared the expression of BRCA1 in thirty-five
      paired tumour specimens versus their corresponding adjacent normal tissue. We
      found two- to five-fold reduced BRCA1 expression levels in tumour specimens as
      compared to normal tissue. Decreased BRCA1 expression was significantly
      associated with loss of heterozygosity (LOH) at the BRCA1 region, as well as with
      negative estrogen receptor (ER) status. Our results offer an alternative
      explanation of how BRCA1 could play an important role in sporadic breast cancer,
      not via mutations in coding sequences but due to transcriptional disregulation.
      Decreased BRCA1 mRNA may be caused due to loss of gene copies, deletions of
      regulatory elements in the BRCA1 promoter or failure of transcriptional
      regulation by estrogen receptors. We also investigated possible relationships
      between BRCA1, p53, mdm-2 and p21(WAF1/CIP1) at the expression level. p53
      expression was unaffected in almost all the specimens, mdm-2 was overexpressed in
      18/35 specimens while 21/35 overexpressed p21. Samples exhibiting reduced BRCA1
      levels simultaneously overexpressed both p21 and mdm-2, showing that BRCA1, at
      certain levels, even reduced up to 2.7-fold, is functional and sufficient to
      upregulate p21, when p53 activity is inhibited by its negative regulator, the mdm
      2. On the contrary, specimens exhibiting more than 2.7-fold reduced BRCA1 levels,
      overexpressed p21 while mdm-2 expression was normal, allowing us to speculate
      that p21 transcriptional activation is due to p53 activity, in cases with
      dramatically decreased BRCA1 expression. Our findings provide evidence,
      indicating that BRCA1 might affect cell cycle regulation and loss of BRCA1
      function due to decreased expression leads to cell cycle arrest, through p53 and
      p21 genes.

PMID- 9535787
TI  - Inhibition of HIV-1 replication by an anti-tat hammerhead ribozyme.
AB  - Tat is a virally expressed regulatory protein involved in the replication of HIV
      1, the etiological agent of AIDS. To investigate the effect of tat inhibition on
      HIV replication, we constructed a retroviral vector to express an anti-tat
      hammerhead ribozyme as part of the 3' untranslated region of beta-galactosidase
      transcripts. Initial testing of this vector in tat-expressing COS-7 cells reduced
      tat activity by 85-95% as measured by tat-dependent CAT assays. Amphotropic and
      HIV-pseudotyped retroviral particles generated with this vector were used in HIV
      challenge experiments to determine the ability of this reagent to control HIV
      replication. CD4(+) peripheral blood lymphocytes (PBLs) stably transduced with
      this vector were subsequently challenged with HIV. These cells were able to
      resist HIV infection for up to 20 days as measured by cell death and reverse
      transcriptase activity. These data yield proof of principle that a pseudotyped
      retroviral vector can target and deliver a protective ribozyme to CD4(+) cells.

PMID- 9535788
TI  - Induction of multidrug resistance gene expression in rat liver cells in response
      to acute treatment by the DNA-damaging agent methyl methanesulfonate.
AB  - Expression of multidrug resistance (mdr) genes encoding the P-glycoprotein (P-gp)
      drug efflux pump was analysed in cultured rat liver epithelial cells acutely
      treated by the DNA-damaging agent methyl methanesulfonate (MMS). Exposure to this
      alkylating agent used at 30 microg/ml for 12 or 24 h was shown to enhance mdr
      mRNA levels in rat liver cells without alteration of cell viability. Induction of
      mdr transcripts occurred through increased expression of the mdr1b gene as
      indicated by reverse transcriptase-polymerase chain reaction analysis using rat
      mdr gene-specific primers and was not associated with up-regulation of cytochrome
      P-450 1A1, thereby suggesting that this detoxifying enzyme and P-gp were not
      coordinately regulated by MMS. In addition, the DNA-damaging agent was found to
      enhance in a dose-dependent manner cellular efflux of the P-gp substrate
      rhodamine 123, which was inhibited by the P-gp inhibitor verapamil, thus
      providing evidence that exposure to MMS led to increased P-gp-related drug
      transport in rat liver cells. The up-regulation of functional P-gp expression
      occurring in MMS-treated liver cells may be interpreted as a part of the cellular
      response to DNA damage.

PMID- 9535789
TI  - Selective antagonist for the melanocortin 4 receptor (HS014) increases food
      intake in free-feeding rats.
AB  - Recently, we discovered a cyclic analogue of MSH (melanocyte stimulating
      hormone), HS014, which is the first selective antagonist of the MC4 receptor. We
      have here studied the effects of this peptide on food intake in non-deprived male
      rats. Vehicle or five doses of HS014 (0.1-10 nmol) were administered ICV at
      midday. HS014 (0.33-3.3 nmol) significantly and in a dose-dependent manner
      increased food intake for the first 1 h. At 4 h after the injections, food intake
      was also significantly increased in rats treated with 1 and 3.3 nmol of HS014,
      whereas the lowest dose tested (0.1 nmol) was without effect. Cumulative food
      intake increased to 100% at 4 h after the injections. The highest dose of HS014
      (10 nmol) induced sedation and inhibited feeding for first hour of testing.
      However, this dose also increased food consumption later. These data demonstrate
      that attenuation of central melanocortinergic tone with HS014 induces
      disinhibition of feeding and provides additional evidence for the hypothesis that
      activation of the MC4 receptor inhibits food intake. HS014 may be a useful tool
      for elucidating the role of the MC receptor subtypes in vivo. This is the first
      report demonstrating an increase in daytime food intake in free-feeding animals
      caused by a MC receptor active agent.

PMID- 9535790
TI  - Germ cell nuclear factor is a response element-specific repressor of
      transcription.
AB  - We have shown that the orphan receptor Germ Cell Nuclear Factor (GCNF) binds to a
      direct repeat of the sequence AGGTCA with zero base pair spacing (DR0). Here, we
      further characterize the binding characteristics of GCNF. We demonstrate that
      GCNF binds specifically to DR0s as a homodimer, and does not bind with high
      affinity to DR1-DR6 sequences. GCNF is the first nuclear receptor shown to bind
      specifically to DR0s. The wild type GCNF is unable to transactivate the reporter
      plasmid DR0(2)tkCAT. Lacking a ligand to activate GCNF, we fused the activation
      domain from the viral protein VP16 to GCNF, and observed activation of
      DR0(2)tkCAT. This activation is specifc to DR0s, and is not observed when that
      sequence is replaced by DR1-DR6 sequences. In addition GCNF does not
      transactivate through an SF-1 response element. At increasing concentrations,
      wild type GCNF is able to repress basal transcription. Repression is again
      specific to DR0s. The preference of GCNF for the DR0 sequence both in vitro and
      in transfections suggests that GCNF defines a novel nuclear receptor signaling
      pathway.

PMID- 9535791
TI  - Selenoproteins are expressed in fetal human osteoblast-like cells.
AB  - Selenoproteins are involved in mechanisms of cell differentiation and defense. We
      investigated the expression of glutathione peroxidases, as well as other
      selenoproteins, in fetal human osteoblasts (hFOB-cells). Using 75-selenium
      metabolic labelling of viable hFOB-cells, we identified several selenoproteins in
      cell lysates of about 45-80 kDa and in the migration range of 14 kDa to 24 kDa.
      Cells expressed low mRNA levels of both cellular glutathione peroxidase and
      plasma glutathione peroxidase mRNA as analysed by Southern analysis of RT-PCR
      products. Basal cellular glutathione peroxidase enzyme activity in hFOB-cells
      (19.7 nmol NADPH oxidised per min and microg protein) was further increased 2.5
      fold by the addition of 100 nM sodium selenite to the culture medium for 3 days.
      Furthermore, expression of selenoprotein P mRNA was demonstrated by RT-PCR. hFOB
      cells did not show activities of the selenoproteins type I or type II 5'
      deiodinase. In summary, we identified cellular glutathione peroxidase, plasma
      glutathione peroxidase and selenoprotein P among of a panel of several 75
      selenium labelled proteins in human fetal osteoblasts. The expression of
      selenoproteins like glutathione peroxidases in hFOB-cells represents a new system
      of osteoblast antioxidative defense that may be relevant for the protection
      against hydrogen peroxide produced by osteoclasts during bone remodelling.

PMID- 9535793
TI  - Characterization of the gene encoding the human type II cGMP-dependent protein
      kinase.
AB  - The type II cGMP-dependent protein kinase (cGK) plays a pivotal role in the
      regulation of intestinal fluid balance in man. Furthermore, mice carrying a null
      mutation for the gene encoding the type II cGK develop as dwarfs indicating that
      this enzyme has other less characterized roles. The present report describes the
      isolation and characterization of bacterial artificial chromosome (BAC)- and P1
      derived artificial chromosome (PAC)-clones containing the gene encoding the human
      type II cGK. The gene was estimated to cover at least 125 kb and consisted of 19
      exons separated by introns of various lengths. The splice junctions of the type
      II cGK gene corresponded well with the structure of the gene encoding human type
      I cGK and with the splice junctions observed in the Drosophila melanogaster DG2
      gene. 5'-rapid amplification of cDNA-ends established the presence of a non
      translated exon.

PMID- 9535792
TI  - Cloning and analysis of the promoter activity of the human prostatic acid
      phosphatase gene.
AB  - Human prostatic acid phosphatase (PAP) has been proposed to be a prostate
      epithelium differentiation antigen and its expression can be regulated by
      androgen. Nevertheless, the regulatory mechanism at the molecular level is not
      completely understood. In this communication, we demonstrated the tissue-specific
      expression of PAP in the normal prostate epithelium. Furthermore, results of
      nuclear run-on experiments indicated that androgen could regulate the
      transcriptional rate of the PAP gene. This mode of regulation was modulated by
      cell density. To investigate the transcriptional regulation, we cloned and
      characterized a 1.4- kilobase (kb) fragment of DNA that flanks the 5' region of
      the PAP gene from LNCaP human prostate carcinoma cells. The results demonstrated
      that this 1. 4-kb DNA fragment can drive a chloramphenicol acetyltransferase
      (CAT) gene expression in LNCaP cells. Also, the promoter activity was inversely
      correlated with the growth of those cells.

PMID- 9535794
TI  - Identification of alternatively spliced transcripts encoding murine macrophage
      colony-stimulating factor.
AB  - We have isolated a novel cDNA encoding macrophage colony-stimulating factor (M
      CSF) from a murine stromal cell line, ST2. The cDNA included an entire coding
      sequence of the M-CSF gene but contained an additional sequence of 140 base pairs
      (bp). Northern blot analysis demonstrated that other murine cell lines such as a
      fibroblastic cell line (L) and a stromal cell line (PA6) also expressed the
      transcripts corresponding to the clone. The nucleotide sequence analyses of the
      cDNA and the cloned M-CSF genome revealed that the 140-bp insertion sequence was
      part of intron 1 which separated exon 1 and exon 2: the former contained part of
      the amino acid residues of the signal sequence and the latter the rest of the
      signal sequence and the first 22 amino acid residues of the mature protein. The
      insertion of the 140-bp intron sequence not only changed the amino acid sequence
      of the signal peptide but also generated an in-frame termination codon. However,
      instead of the dysfunction of the original initiation codon, the 140-bp insertion
      sequence contained a putative ATG initiation codon that preserved the original
      open reading frame. Finally, we found that the cDNA directed the expression of a
      secreted and biologically active M-CSF protein when it was introduced into COS7
      cells and M-CSF activity in the culture supernatants was measured using an M-CSF
      dependent cell line. These results indicate the presence of an alternatively
      spliced M-CSF transcript which utilizes an alternate initiation codon in order to
      specify active M-CSF protein.

PMID- 9535795
TI  - Molecular cloning of ssd-form neural cell adhesion molecules (N-CAMs) as the
      major form in Xenopus heart.
AB  - Different forms of neural cell adhesion molecule (N-CAM) are generated by
      alternative splicing of primary transcripts and considered to have distinct
      biological functions. We cloned cDNAs encoding a new form of N-CAMs from the
      Xenopus heart cDNA library. Comparison of the sequences with chicken and mouse N
      CAMs revealed that these clones code for ssd-form N-CAM. We demonstrate by
      Northern blot analysis that the ssd form is the major form expressed in the
      Xenopus adult heart. We obtained two types of ssd-form N-CAM, which are
      transcripts from N-CAM 1 and N-CAM 2 genes. Both types contain muscle specific
      domain (MSD) but not pi domain. Northern blot analysis also indicated that this
      form is not expressed in adult brain, in which ld-form N-CAM is the main N-CAM
      expressed. It is possible that high levels of specific expression of ssd-form N
      CAM are related with the differentiation of cardiac muscles.

PMID- 9535796
TI  - Elicitins, proteinaceous elicitors of plant defense, are a new class of sterol
      carrier proteins.
AB  - Some phytopathogenic fungi within Phytophthora species are unable to synthesize
      sterols and therefore must pick them up from the membranes of their host-plant,
      using an unknown mechanism. These pseudo-fungi secrete elicitins which are small
      hydrophilic cystein-rich proteins. The results show that elicitins studied
      interact with dehydroergosterol in the same way, but with some time-dependent
      differences. Elicitins have one binding site with a similar strong affinity for
      dehydroergosterol. Using a non-steroid hydrophobic fluorescent probe, we showed
      that phytosterols are able to similarly bind to elicitins. Moreover, elicitins
      catalyze sterol transfer between phospholipidic artificial membranes. Our results
      afford the first evidence for a molecular activity of elicitins which appears to
      be extracellular sterol carrier proteins. This property should contribute to an
      understanding of the molecular mechanism involved in sterol uptake by
      Phytophthora. It opens new perspectives concerning the role of such proteins in
      plant-microorganism interactions, since elicitins trigger defence reactions in
      plants.

PMID- 9535797
TI  - Antibodies directed against ZAP-70 cross-react with a 66 kDa tyrosine kinase in
      the rat brain.
AB  - ZAP-70 is another member of Syk family tyrosine kinases which plays an essential
      role in growth, differentiation, and function of T lymphocytes. In this study, we
      report the specific expression of a 66 kDa tyrosine kinase that is specifically
      cross-reacted with anti-ZAP-70 antibodies in the developing neurons. By
      immunoblot and immunoprecipitation assay using various anti-ZAP-70 antibodies, a
      66 kDa tyrosine kinase was detected in lysates from rat brain. During the
      development of rat brain, expression levels of this 66 kDa tyrosine kinase were
      highest around 3 weeks after birth and decreased thereafter in the adult. In
      addition, immunoblot analysis demonstrated that this 66 kDa tyrosine kinase was
      expressed almost solely in the nervous system. These results suggest that this
      ZAP-70-related tyrosine kinase may play an important role in growth and
      differentiation in the developing neurons. Our observations will provide the clue
      to approach the regulatory system common to neurogenesis and immune response.

PMID- 9535798
TI  - Cloning and expression of the ataxia-telangiectasia gene in baculovirus.
AB  - The gene mutated in the human genetic disorder ataxia-telangiectasia, ATM, is
      implicated in the response to radiation-induced DNA damage and to a more
      widespread signalling defect. The ATM protein is predominantly a nuclear protein
      where it interacts with p53 and c-Abl as part of a radiation signal transduction
      pathway(s). We describe here the cloning of full-length ATM cDNA in a baculovirus
      vector to produce recombinant protein. Expression of ATM, as a soluble protein,
      was observed by 36 h post-infection using immunoblotting with anti-ATM antibody.
      The presence of a hexahistidine tag on ATM was used as the basis for purification
      of the protein by affinity chromatography. The protein yield was only 20 ng/100
      ml of infected cells, presumably because of the size of the protein and adverse
      effects on cell growth when overexpressed. ATM was found to have
      autophosphorylation activity in immunoprecipitates with antibodies directed
      against the hexahistidine tag sequence. These results demonstrate that ATM can be
      expressed inefficiently in baculovirus infected insect cells and the data suggest
      that it phosphorylates itself.

PMID- 9535799
TI  - Refolding of denatured trichosanthin in the presence of GroEL.
AB  - The stability of trichosanthin (TCS), a 27-kDa ribosome-inactivating protein, was
      investigated in the presence of guanidinium chloride (GdnHCl). The process of
      unfolding was monitored by CD and fluorescence spectroscopy. Both methods show
      the presence of partially folded intermediates. Unfolding of TCS is attained in
      6M GdnHCl, but the inactive species recover a good deal of its DNase activity
      upon dilution with buffer containing GroEL and ATP. The mechanism of recognition
      of unfolded TCS by GroEL was studied by fluorescence spectroscopy.

PMID- 9535800
TI  - Inositol 1,4,5-trisphosphate induced Ca2+ release from chloroquine-sensitive and 
      insensitive intracellular stores in the intraerythrocytic stage of the malaria
      parasite P. chabaudi.
AB  - Isolated P. chabaudi parasites were permeabilized with digitonin and the function
      of intracellular Ca2+ stores was studied using the Ca2+ indicators arsenazo III
      or Fluo 3-acid in the medium. Addition of the second messenger InsP3 (5 microM)
      to permeabilized parasites leads to Ca2+ release into the medium, with the mean
      extent of release being 40 nmol Ca2+/10(8) cells. This Ca2+ release was
      completely abolished in the presence of heparin, an InsP3 receptor antagonist.
      The amount of Ca2+ released was approximately 50% reduced when InsP3 was added
      subsequent to the discharge of the endoplasmic reticulum (ER) Ca2+ pool with the
      SERCA (sarcoplasmic ER Ca2+ ATPase) inhibitors thapsigargin and tBHQ (2,5-di(ter
      butyl)-1,4 benzohydroquinone). The thapsigargin- and tBHQ-sensitive pool account
      for 20 nmol of Ca2+/10(8) cells. If InsP3 was added after the discharge of the
      residual Ca2+ by addition of either the K+/H+ uncoupler nigericin or the
      antimalarial drug chloroquine, no further Ca2+ release was observed. This is the
      first report of InsP3-induced Ca2+ release in a parasite protozoa. In addition
      our finding that chloroquine depletes an InsP3-sensitive Ca2+ compartment, raises
      the possibility that the InsP3-dependent Ca2+ release from this store might be
      important for the regulation of growth and differentiation of the parasite.

PMID- 9535801
TI  - The generation of superoxide anions in glycation reactions with sugars, osones,
      and 3-deoxyosones.
AB  - Glycoxidation is a process whereby glycated proteins chemically generate oxygen
      free radicals. Superoxide anion formation was measured by the superoxide
      dismutase-dependent reduction of ferricytochrome C in glycation reactions at pH
      7.0 in the absence of transition metal ions. Assays were linear over 1 h, and
      most activity was seen after a 2 d incubation of 5 mM L-threose and 10 mM alpha-N
      acetyl-lysine (N-Ac-Lys) or 10 mg/mL RNase A. Trioses, tetroses and their
      corresponding osones and 3-deoxyosones had the highest activity (12-16 nmoles O.
      2/hr/ml) with N-Ac-Lys. Osones and 3-deoxyosones alone generated considerable O.
      2, whereas aldose sugars largely did not. Xylosone and 3-deoxyxylosone produced 6
      and 10 nmoles O.-2/hr/ml respectively with N-Ac-Lys, however, xylose was
      inactive, as were glucose and fructose. Glycation assays with 3-deoxyglucosone
      and glyoxal showed no activity, however, methyl glyoxal generated 1.7 and 2.0
      nmoles O.-2/hr/ml with N-Ac-Lys and N-Ac-Arg, respectively. Therefore, Amadori
      compounds composed of lysine and short chain sugars can rapidly generate
      superoxide anion in the absence of metal ions.

PMID- 9535802
TI  - Secretion of heterologous proteins from Schizosaccharomyces pombe using the
      homologous leader sequence of pho1+ acid phosphatase.
AB  - In this study we report the use of the S. pombe leader sequence of pho1+ acid
      phosphatase (Elliott et al., J. Biol. Chem. 216, 2916-2941, 1986) for the
      secretion of heterologous proteins into the medium. The green fluorescent protein
      (GFP) and the Human Papillomavirus (HPV) type 16 E7 protein are normally not
      secreted; fusion of the S. pombe pho1 leader peptide (SPL) to GFP and HPV 16 E7
      resulted in an efficient secretion of these proteins although the latter contains
      a nuclear targeting sequence. These data suggest that SPL fused constructs could
      be applied for the production of other recombinant proteins using the S. pombe
      expression system. Furthermore, since GFP retains its intrinsic fluorescence
      during the secretion, this system may be useful to study the secretory pathway of
      fission yeast in vivo.

PMID- 9535803
TI  - CD44 isoforms, including the CD44 V3 variant, are expressed on endothelium,
      suggesting a role for CD44 in the immobilization of growth factors and the
      regulation of the local immune response.
AB  - Endothelium plays a central role in the regulation of site and inflammation
      specific leukocyte migration. Some of the mediators involved in leukocyte
      migration, such as chemokines, can bind to heparan sulfate on the endothelium
      resulting in immobilization near their sites of production. Because CD44 variants
      expressing V3 have been shown to carry heparan sulfate side chains and to
      interact through these side chains with heparan sulfate binding growth factors,
      we investigated the expression of CD44 variants on endothelium. We found a strong
      expression of V5, V7-8 and V10 CD44 variants and a weaker expression of V3 and V6
      CD44 variants on endothelium by using immuno-histochemistry and by FACS analysis.
      Expression of CD44 V3 variants was confirmed at both the protein and mRNA levels
      by Western blotting and by reverse transcriptase-PCR respectively. Expression of
      CD44 variants was unaffected by IL-1beta, IL-8, TNFalpha, IFNgamma or IL-4
      treatment, indicating either constitutive expression of these variants or
      involvement of other cytokines in their regulation.

PMID- 9535804
TI  - Expression pattern of the C. elegans P21-activated protein kinase, CePAK.
AB  - The C. elegans p21-activated protein kinase (CePAK) has a high amino-acid
      sequence similarity to mammalian PAKs. Tissue specificity of the expression of
      CePAK was examined using lacZ and GFP reporters. This analysis indicated that
      CePAK is expressed mainly in pharyngeal muscles, the CAN neurons, and motor
      neurons in the ventral nerve cord, as well as several cells in the tail region
      and the distal tip cells. The CePAK::GFP fusion protein was preferentially
      localized to the cell surface in pharyngeal muscles.

PMID- 9535805
TI  - Maleylated-BSA enhances production of nitric oxide from macrophages.
AB  - Maleylated-bovine serum albumin (maleyl-BSA) elicits transcription and secretion
      of a number of proinflammatory genes via ligation of the low-affinity scavenger
      receptor (SR) on macrophages. We now demonstrate that while neither maleyl-BSA,
      nor interferon-gamma (INF-gamma) alone induce nitric oxide (NO) production, when
      combined they promote release of NO from murine peritoneal macrophages. This
      effect was blocked by treatment with oxidized-low density lipoprotein. Maleyl-BSA
      activated NF-kappaB dimers capable of binding the NF-kappaBd sequence unique to
      the iNOS promoter, but this failed to induce significant new transcription or
      accumulation of iNOS mRNA. The combination of maleyl-BSA and IFN-gamma failed to
      demonstrate synergy at the transcriptional or mRNA levels, as these levels were
      comparable to those elicited by IFN-gamma alone. These studies suggest that the
      synergy in NO production between maleyl-BSA and IFN-gamma occurs after the
      accumulation of iNOS-specific mRNA, possibly at the translational or post
      translational level.

PMID- 9535806
TI  - Evidence of association of the ecNOS gene polymorphism with plasma NO metabolite
      levels in humans.
AB  - Nitric oxide (NO) synthesized by the vascular endothelium regulates mammalian
      blood vessels and other systems in humans. Recently, an endothelial nitric oxide
      synthase (ecNOS) gene polymorphism, the 27-bp repeat in intron 4 (ecNOS4), was
      reported to be related to the pathogenesis of coronary heart disease and terminal
      renal failure. We analyzed this polymorphism in a group of 413 healthy subjects,
      and measured their plasma nitrite and nitrate (NOx) levels. The frequency of the
      b allele was 89.8% , and the frequency of the a allele was 10.2%. The frequency
      of ecNOS4 b/b, ecNOS4 b/a, and ecNOS4 a/a in the healthy subjects in this study
      was 0.814 (n=336), 0.169 (n=70) and 0.017 (n=7), respectively. Using this
      polymorphism as a DNA marker, we found a strong association between the alleles
      of the ecNOS gene polymorphism and the plasma NOx levels. The basal NO metabolite
      levels were 28.8 micromol/L in subjects with ecNOS4 a/a, 31.4 micromol/L in those
      with ecNOS4 b/a, and 35.5 micromol/L in those with ecNOS4 b/b. The mean plasma
      NOx level of the subjects who were homozygous for the a allele was nearly 20%
      lower than in the subjects with the b allele. The plasma NOx level of the
      subjects with the a allele was 31.2+/-2.00 micromol/L, and significantly lower
      than the 35.5+/-0.93 micromol/L in those without the a allele (P <0.05). The
      results of this study indicate that the ecNOS4 gene locus may be responsible for
      variations in the genetic control of plasma NOx and that analysis of ecNOS4 gene
      polymorphism may be a useful tool for studying the relation between NO and
      diseases.

PMID- 9535807
TI  - The apolipoprotein(a) promoter contains a retinoid response element.
AB  - Retinoids were previously shown to lower apolipoprotein(a) [apo(a)] mRNA levels,
      suggesting that the apo(a) promoter contains a retinoid response element (RRE).
      Scanning the apo(a) promoter for sequences related to the consensus RRE half-site
      (5'-PuG(G/T)TCA-3') uncovered four sites that could potentially function as RREs
      at -2915, -1875, -1036, and -407. The activity of these sites was assessed by
      their ability to compete with a very strong consensus DR5 RRE for binding to
      retinoic acid receptor (RARalpha) and retinoid X receptor (RXRalpha) heterodimers
      using electrophoretic mobility-shift assays. Only the -1036 site (5'
      TGACCTTGTGATCC-'3) was an effective competitor of the DR5 RRE; therefore, it was
      designated as apo(a) RRE. Apo(a) RRE competed with DR5 RRE for RARalpha/RXRalpha
      binding with 1/10 the affinity of DR5 RRE, while a scrambled apo(a) RRE was
      inactive. These results suggested that apo(a) RRE is a potential candidate for
      mediating the effect retinoids have on apo(a) mRNA expression.

PMID- 9535808
TI  - Ubiquitous presence of cellular proteins that specifically bind to the 3'
      terminal region of hepatitis C virus.
AB  - The 3' terminal region (3'-X tail) of hepatitis C virus (HCV) genomic RNA forms a
      stable stem-loop structure. The 3'-X tail consists of 98 nucleotides (nt) that
      are highly conserved among the HCV strains and supposed to function as a cis
      acting region for replication of negative strand RNA and/or viral encapsidation.
      In the present study, by UV cross-linking assay we found two kinds of cellular
      proteins of approximately 87 and 130 kDa, which specifically bind to the full
      length 3'-X tail (nt 1 to 98), but not the 3'- or 5'-truncated 3'-X tail,
      consisting of nt 1 to 50 or nt 51 to 98, respectively. These proteins were
      detected in human cell lines such as hepatic tumor cell lines and a T-lymphocyte
      cell line and also in a human embryonic lung fibroblast cell strain. In addition,
      human hepatocellular carcinoma tissues expressed these proteins regardless of
      infection or uninfection of HCV. Furthermore, these proteins were also detected
      in normal human tissues derived from the lung, heart, kidney, stomach, intestine,
      and colon. Thus, these cellular proteins, which are ubiquitously present in human
      tissues, might be involved in viral replication and/or encapsidation.

PMID- 9535809
TI  - Selective pituitary resistance to thyroid hormone produced by expression of a
      mutant thyroid hormone receptor beta gene in the pituitary gland of transgenic
      mice.
AB  - Resistance to thyroid hormone (RTH) has been subdivided into generalized
      resistance (GRTH) and pituitary resistance (PRTH) based on the clinical
      impression of absence or presence of thyrotoxicosis. However, due to lack of
      objective clinical and genetic criteria, the existence of PRTH as a distinct
      entity became controversial. To determine what the phenotype would be if RTH was
      confined to the pituitary, a transgenic mouse was developed in which expression
      of the mutant thyroid hormone receptor (TR) beta (G345R) was targeted to the
      pituitary thyrotrophs by placing it downstream of the mouse thyrotropin beta
      promoter. This construct exhibited an antagonistic effect on the thyroid hormone
      dependent transactivation, mediated through the wild-type TRbeta1, only when
      cotransfected with the thyrotroph embryonic factor in a heterologous cell line.
      As expected the transgene was transcribed predominantly in the pituitary gland
      but not in liver. These mice showed a significant, though modest, increase in
      serum T4 concentration. A decrease in the serum cholesterol was observed in
      keeping with the selective tissue hyposensitivity to thyroid hormone.

PMID- 9535810
TI  - Hepatocyte growth factor/scatter factor activates the apoptosis signaling pathway
      by increasing caspase-3 activity in sarcoma 180 cells.
AB  - Hepatocyte growth factor, which is now known to be the same protein as scatter
      factor, induced oligonucleosomal fragmentation of nuclear DNA of Sarcoma 180
      cells and increased the activity of caspase-3, a key component in control of the
      apoptotic cell death pathway to about 2.6 times that in control cells on 48 hr
      incubation, but did not increase the activity of caspase-1. Both HGF-induced DNA
      fragmentation and caspase-3 activity were completely inhibited by co-incubation
      with an inhibitor of caspase-3, Ac-DEVD-H. In contrast, HGF did not affect the
      expression of the apoptosis suppressors Bcl-2 and Bcl-x. These results indicate
      that HGF activates the apoptosis signaling pathway by increasing caspase-3
      activity in Sarcoma 180 cells.

PMID- 9535811
TI  - Increase of neuronal nitric oxide synthase in rat skeletal muscle during ageing.
AB  - Nitric oxide synthases (NOS) are different widely expressed enzymes which produce
      the molecular messenger nitric oxide. The neuronal isoform of NOS (nNOS) is
      involved in several processes of the cell metabolism, most of which are, at
      present, not fully understood (neurotransmission, smooth muscle motility,
      myoblast and myocyte biology and others). In skeletal muscle nNOS is present
      mainly at the plasmalemma, where it is attached to the dystrophin-related
      proteins; in fact, in pathologies involving dystrophin, nNOS is altered as well.
      We report that in aged rats the nNOS amount in skeletal muscle increases both in
      the soluble and microsomal fractions and that an additional intracytoplasmic
      localisation appears.

PMID- 9535812
TI  - Calcium and insulin-like growth factor I stimulation of sodium-dependent
      phosphate transport and proliferation of cultured rat osteoblasts.
AB  - Calcium (Ca) stimulates proliferation of osteoblasts in vitro, an effect proposed
      to be mediated by IGF I. Addition of 1 mM Ca or of 1 nM IGF I to the medium (0.3
      mM Ca) of a rat bone-derived cell line, PyMS, stimulated not only DNA synthesis
      but also sodium-dependent (Nad) phosphate (Pi) uptake, the latter, within 2 h.
      These cells barely express and produce IGF I. IGF binding protein-3 which
      inhibits IGF action decreased neither basal nor Ca-stimulated but IGF I
      stimulated NadPi transport and DNA synthesis, indicating that Ca stimulated NadPi
      transport and DNA synthesis independently of IGF I. The effects of Ca and IGF I
      on DNA synthesis were additive. 1 microM nifedipine blocked IGF I- and Ca
      stimulated DNA synthesis but not NadPi transport, suggesting that Ca influx is
      not mediating the NadPi transport-enhancing IGF I signal but is required for IGF
      I-induced osteoblast proliferation.

PMID- 9535813
TI  - Thyroid hormone regulates expression of shaker-related potassium channel mRNA in
      rat heart.
AB  - Effects of thyroid hormones on cardiac function or rhythm have been known;
      however, the mechanism is still unclear. In the present study examined were
      effects of triiodethyronine (T3) on voltage-gated potassium channel gene
      expression in rat heart since the potassium channels were presumed to modulate
      cardiac functions. The mRNA expression of five voltage-gated potassium channel
      gene alpha subunits (Kv1.2, Kv1.4, Kv1.5, Kv2.1, and Kv4.2) in heart was examined
      by ribonuclease protection assay in rats which were treated with T3 or
      propylthyouracil (PTU). All these genes except Kv1.4 mRNA were apparently
      expressed in the normal rat heart ventricle. Kv1.2 mRNA expression in ventricle
      was markedly suppressed by T3-treatment and enhanced by PTU-treatment.
      Interestingly, upregulation of Kv1.4 mRNA expression and downregulation of Kv1.5
      mRNA expression were concomitantly induced in the ventricle by the PTU-treatment.
      In addition, the downregulation of the ventricular Kv1.5 mRNA expression induced
      by PTU was restored by T3 replacement. No changes of Kv2.1 and Kv4.2 mRNA
      expression were observed in the ventricles by the T3- or PTU-treatment. In heart
      atrium the same findings were observed. Kv1.4 mRNA expression, which was
      detectable in control rat atrium, also decreased significantly by T3-treatment.
      In contrast, no changes of Kv1.2, Kv1.4, and Kv1.5 mRNA expression in rat brains
      were induced by T3-treatment. These findings suggest that thyroid hormone
      specifically influences mRNA expression of Shaker-related potassium channel genes
      in rat hearts through a common T3 receptor-mediated regulation at a
      transcriptional level.

PMID- 9535814
TI  - Preferential expression of the cDNA encoding the proteasome subunit during the
      growth/differentiation transition of Dictyostelium cells.
AB  - A proteasome subunit-1 gene (DAPS-1) was isolated as one preferentially expressed
      during the transition from growth to differentiation in Dictyostelium discoideum
      cells, using the differential display method. The DAPS-1 cDNA sequence with a
      length of 882 bp encodes a protein (Mr. 23.4 kDa) consisting of 213 amino acids.
      The deduced amino acid sequence of DAPS-1 showed 61% and 58% identity to the
      proteasome subunit Y of Xenopus laevis and Homo sapiens, respectively and 48% and
      47% identity to the proteasome subunit LMP2 of Homo sapiens and Orizas latipes,
      respectively. Northern analysis revealed that a 1.0 kb of DAPS-1 mRNA is
      predominantly expressed during the early stage of differentiation induced by
      starvation. This seems to indicate that the DAPS-1 protein may be involved in
      proteolysis coupled with active exchange of the cellular protein composition
      during the phase-shift of Dictyostelium cells from the proliferative to
      differentiated state.

PMID- 9535815
TI  - Uptake and gene expression of naked plasmid DNA in cultured brain microvessel
      endothelial cells.
AB  - Cellular uptake and gene expression of plasmid DNA and its cationic liposome
      complexes were studied using primary cultures of bovine brain microvessel
      endothelial cells (BMEC) developed as an in vitro model of the blood-brain
      barrier. An avid association of naked plasmid DNA with the BMEC monolayer was
      observed at 37 degreesC, which is comparable to that of the DNA/liposome complex.
      The cellular association significantly decreased at low temperature (4 degreesC).
      The binding at 4 degreesC was saturable and significantly inhibited by polyanions
      involving polyinosinic acid and dextran sulfate, typical ligands for the
      macrophage scavenger receptors, but not by polycytidylic acid or in the presence
      of EDTA. Unexpectedly, a significant gene expression in the BMEC was obtained by
      transfection with naked plasmid DNA although the expression level was lower than
      that obtained by plasmid DNA/cationic liposome complex. Taken together, cultured
      capillary endothelial cells derived from the brain are able to take up naked
      plasmid DNA via a scavenger receptor like-mediated mechanism for polyanions and
      gene expression in the cells takes place.

PMID- 9535816
TI  - Shedding of CD44 from PMA-differentiated U-937 cells is enhanced by treatment
      with mineral particles.
AB  - In this report, we show that enhanced shedding of CD44 might contribute to the
      down-regulation of this receptor observed after phagocytosis of MnO2 particles by
      PMA-differentiated U-937. The apparent Mr of the soluble CD44 detected in culture
      supernatants was slightly lower than that of the membrane form suggesting that
      shedding resulted from proteolytic cleavage. Increased shedding of CD44 was also
      noted with other mineral particles (chrysotile and DQ12) but to a lower extent
      whereas some (TiO2 and amosite) had no effect on this process. These results
      indicate that shedding enhancement was particle-specific rather than a general
      consequence of phagocytosis. The ability of the particles to enhance CD44
      shedding was not directly dependent on their cytotoxic potency. Different
      patterns of reactivity were noted with CD11b, suggesting that the underlying
      mechanisms are specific.

PMID- 9535817
TI  - Isolation and characterization of an invertase and its repressor genes from
      Schizosaccharomyces pombe.
AB  - PCR was used to isolate an invertase homolog gene from the fission yeast
      Schizosaccharomyces pombe. The cloned inv1(+) gene encodes a protein of 581 amino
      acids with 16 potential asparagine-linked glycosylation sites, and has 39% and
      38% identity to the Schwanniomyces occidentalis and Saccharomyces cerevisiae SUC2
      invertases. When the inv1(+) gene was disrupted, S. pombe strains lacked
      detectable invertase activity. This result showed that the inv1(+) gene encodes
      only one active invertase in S. pombe cells. The transcription of inv1(+) is
      repressed in the presence of glucose. The transcription of inv1(+) was not
      affected in cyr1Delta strain which lacks adenylate cyclase activity, unlike
      transcription of S. pombe fbp1(+) gene. We have identified an S. pombe gene
      (scr1(+)) that encodes a homolog of the Aspergillus nidulans CREA which is
      required for glucose repression of the glyconeogenic pathway. Although the
      deletion of scr1(+) did not influence the transcription of fbp1(+) gene, glucose
      repression of the inv1(+) gene was severely affected. These results showed that
      glucose repression of inv1(+) gene is dependent on scr1(+) gene, and S. pombe
      cAMP signalling pathway may not be essential for glucose repression of inv1(+)
      gene.

PMID- 9535818
TI  - Estrogens cause rapid activation of IP3-PKC-alpha signal transduction pathway in
      HEPG2 cells.
AB  - The mechanisms through which steroids affect target cells are not fully
      understood. In addition to the classic model, there is now increasing evidence
      that steroids can exert rapid actions. It must still be elucidated if rapid and
      slow estrogen actions produce co-operative and/or integrative functions. The
      effects of estrogen on inositol trisphosphate (IP3) production and PKC-alpha
      levels on membrane in the HEPG2 cell line have been investigated. Results show
      that estrogen addition to HEPG2 cells causes a rapid increase of IP3 production.
      The effect was totally inhibited by pre-incubation with tyrosine-kinase inhibitor
      genisteine and with the anti-estrogen ICI 182,780. An increased PKC-alpha level
      on the membrane fraction was present 30 min after estrogen exposure. The strong
      signal could elicit a variety of cellular responses such as modulation of ion
      channel, stimulation of cell proliferation, and phosphorylation of cytosolic ER.
      The ability of estrogen to trigger IP3 production in human hepatoma cells is a
      novel aspect of estrogen action that requires the current model of hormone
      stimulation target cells to be revised.

PMID- 9535819
TI  - Importance of hydrophobic region in amphiphilic structures of alpha-helical
      peptides for their gene transfer-ability into cells.
AB  - It has been showned that cationic alpha-helical peptides can be useful as nucleic
      acid-carrier molecules for gene transfer into cells. In order to investigate the
      significancemake sure of importance of the hydrophobic region in amphiphilic
      peptides in relation to their transfection ability, we have employed five kinds
      of peptides with a systematically varied hydrophobic-hydrophilic balance in the
      amphiphilic structures, and have evaluated the relationship between the structure
      and the gene transfer ability of the peptides into COS-7 cells. The peptides with
      a large hydrophobic region took alpha-helical structures, formed large aggregates
      and showed high transfection efficiency. Their high efficiency can be explained
      on the basis of their ability to form stable aggregates which can be internalized
      by endocytosis and remain resistant to digestion in lysosomal vesicles.
      Furthermore, it was suggested that the hydrophobic region of peptides plays an
      important role in the disruption of the endosomal membrane, which ca prevent the
      degradation of DNA in lysosomal vesicles. When peptides do not have so strong
      membrane-disruptive activity, but form aggregates which can be incorporated by
      endocytosis, the transfection efficiency can be recovered by the addition of an
      endosome-disruptive peptide.

PMID- 9535821
TI  - Absence of an obvious molecular imprinting mechanism in a human fetus with
      monoallelic IGF2R expression.
AB  - We have previously shown that, in contrast to its murine homologue, the human
      IGF2R gene is not imprinted. However, in a small number of individuals, partial
      or complete repression of the paternal allele has been observed and it has been
      speculated that in man, IGF2R imprinting is a polymorphic trait. We have
      confirmed monoallelic IGF2R expression in one fetus and investigated whether
      genomic imprinting was involved in the silencing of the paternal allele. Two CpG
      rich regions, known to be important for the imprinted expression of Igf2r in
      mice, were examined for sequence and methylation changes. A 17 bp deletion was
      identified within the intronic CpG island. This deletion was shown to be
      polymorphic and without consequence for the expression of the relevant IGF2R
      allele. Furthermore, in this fetus, methylation patterns of the intronic and
      promoter CpG islands were identical to that of normal controls, including
      hypomethylation of the paternal promoter region. In mice, this region is
      hypermethylated on the paternal allele which is silenced. The absence of paternal
      promoter methylation indicates that paternal silencing in this particular fetus
      is by a mechanism other than parental imprinting or, alternatively, that promoter
      methylation is not necessary for IGF2R imprinting.

PMID- 9535820
TI  - Extracellular signal-regulated kinase (ERK) activity is required for TPA-mediated
      inhibition of drug-induced apoptosis.
AB  - Leukemia cells respond to toxic stimuli by undergoing a form of programmed cell
      death known as apoptosis. However, the signaling events responsible for the
      execution of this form of death are poorly understood. Mitogen-activated protein
      kinase (MAPK) signaling cascades are involved in the cellular response to
      extracellular stimuli. Specifically, extracellular signal-regulated kinases
      (ERKs) have been associated with proliferation and differentiation, whereas the c
      Jun N-terminal kinase/stress-activated protein kinases (JNK/SAPKs) have been
      implicated in cell arrest and death. We report the use of 12-O
      tetradecanoylphorbol-13-acetate (TPA) in the inhibition of apoptosis in HL-60
      cells stimulated with the JNK/SAPK activator anisomycin. This anti-apoptotic
      effect was accompanied by a sustained increase in ERK activity. Furthermore, the
      use of protein kinase C (PKC) inhibitors suggested that PKC was involved in the
      induction of ERK activity and in the inhibition of apoptosis by TPA since the
      inhibition of apoptosis was attenuated when cells were pretreated with PKC
      inhibitors. Lastly, we observed that the use of the MEK1 inhibitor PD98059
      inhibited TPA-mediated ERK activity and abrogated the anti-apoptotic effects of
      TPA. However, apoptotic inhibition was not solely ERK-dependent since cells
      lacking JNK/SAPK stimulation did not undergo apoptosis. Therefore, we conclude
      that TPA inhibits the induction of apoptosis in anisomycin-treated HL-60 cells
      through an ERK-dependent pathway and that this effect can be reversed by the
      attenuation of ERK activity accompanied with the stimulation of JNK/SAPK
      activity.

PMID- 9535822
TI  - Induction of apoptosis by hepatocyte growth factor/scatter factor and its
      augmentation by phorbol esters in Meth A cells.
AB  - Hepatocyte growth factor/scatter factor (HGF/SF) is a multifunctional cytokine
      with mitogenic, motogenic, and morphogenic activities. In addition, HGF/SF
      inhibits the proliferation of some tumor cell lines, but its mechanism remains
      poorly understood. We determined in this study whether HGF/SF induces cell death
      of a Meth A mouse sarcoma cell line in vitro, whose proliferation is remarkably
      suppressed by HGF/SF. Inhibition of Meth A cell growth by HGF/SF was dose
      dependent and maximal at a concentration of 30 ng/ml. The percentage of dead
      cells increased to 22% upon treatment with 30 ng/ml of HGF/SF for 96 h, whereas
      that in untreated cultures was less than 5%. Staining of these cells nuclei with
      Hoechst 33342 revealed condensation of the chromatin and nuclear fragmentation.
      Gel electrophoresis of DNA from HGF/SF-treated cells showed a typical ladder
      pattern. Cells with a fractional DNA content also increased five-fold in the
      HGF/SF-treated cultures as analyzed by flow cytometry after propidium iodide
      staining. These are features typical of apoptosis. Concurrent addition of 12-O
      tetradecanoylphorbol 13-acetate (TPA) with HGF/SF augmented the apoptosis induced
      by the growth factor, while TPA alone caused little death. This enhancement was
      largely blocked by addition of the specific protein kinase C inhibitor GF
      109203X. These results indicate that HGF/SF induced the apoptotic cell death of
      the Meth A sarcoma cell line and that protein kinase C activation augmented the
      growth factor-induced apoptosis.

PMID- 9535824
TI  - Lactacystin, proteasome function, and cell fate.

PMID- 9535823
TI  - Gene expression of neurotrophins and their receptors in cultured rat vascular
      smooth muscle cells.
AB  - Most previous researches on neurotrophins including nerve growth factor (NGF),
      brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3) have focused
      on the nervous system, because their receptors are widely distributed in neuronal
      tissues. Recently, however, the participation of neurotrophins in inflammation
      and atherosclerosis has been proposed. Therefore, the gene expression of
      neurotrophins is now an urgent issue is to be investigated in nonneuronal
      tissues. Here, we evaluated the gene expression of neurotrophins and their
      receptors in rat cultured vascular smooth muscle cells (VSMCs) by the reverse
      transcriptase-polymerase chain reaction method. The transcripts of NGF, NT-3, and
      TrkC (high-affinity receptor for NT-3), and two BDNF alternative spliced
      transcript variants with exons 3 and 4 were clearly detected in VSMCs cultured
      under conventional culture conditions. The upregulation of mRNA levels for NGF,
      two BDNF variants with exons 1 and 2, low-affinity neurotrophin receptor, and
      high-affinity receptors, TrkA (for NGF) and TrkB (for BDNF), was observed in
      response to the treatment with serum and phorbol-ester following the serum
      starvation. In contrast, the expression of NT-3 and TrkC genes was downregulated
      under these conditions. Co-expression of these factors and their receptors and
      the characteristic regulation of their gene transcriptions suggest that these
      factors play crucial roles in the function of VSMCs through an autocrine
      mechanism.

PMID- 9535825
TI  - Interaction between a cellular protein that binds to the C-terminal region of
      adenovirus E1A (CtBP) and a novel cellular protein is disrupted by E1A through a
      conserved PLDLS motif.
AB  - Adenovirus E1A proteins immortalize primary animal cells and cooperate with
      several other oncogenes in oncogenic transformation. These activities are
      primarily determined by the N-terminal half (exon 1) of E1A. Although the C
      terminal half (exon 2) is also essential for some of these activities, it is
      dispensable for cooperative transformation with the activated T24 ras oncogene.
      Exon 2 negatively modulates in vitro cooperative transformation with T24 ras as
      well as the tumorigenic and metastatic potentials of transformed cells. A short C
      terminal sequence of E1A governs the oncogenesis-restraining activity of exon 2.
      This region of E1A binds with a cellular phosphoprotein, CtBP, through a 5-amino
      acid motif, PLDLS, conserved among the E1A proteins of human adenoviruses. To
      understand the mechanism by which interaction between E1A and CtBP results in
      tumorigenesis-restraining activity, we searched for cellular proteins that
      complex with CtBP. Here, we report the cloning and characterization of a 125-kDa
      protein, CtIP, that binds with CtBP through the PLDLS motif. E1A exon 2 peptides
      that contain the PLDLS motif disrupt the CtBP-CtIP complex. Our results suggest
      that the tumorigenesis-restraining activity of E1A exon 2 may be related to the
      disruption of the CtBP-CtIP complex through the PLDLS motif.

PMID- 9535826
TI  - Cryo-crystallography of a true substrate, indole-3-glycerol phosphate, bound to a
      mutant (alphaD60N) tryptophan synthase alpha2beta2 complex reveals the correct
      orientation of active site alphaGlu49.
AB  - The reversible cleavage of indole-3-glycerol by the alpha-subunit of tryptophan
      synthase has been proposed to be catalyzed by alphaGlu49 and alphaAsp60. Although
      previous x-ray crystallographic structures of the tryptophan synthase alpha2beta2
      complex showed an interaction between the carboxylate of alphaAsp60 and the bound
      inhibitor indole-3-propanol phosphate, the carboxylate of alphaGlu49 was too
      distant to play its proposed role. To clarify the structural and functional roles
      of alphaGlu49, we have determined crystal structures of a mutant (alphaD60N)
      alpha2beta2 complex in the presence and absence of the true substrate, indole-3
      glycerol phosphate. The enzyme in the crystal cleaves indole-3-glycerol phosphate
      very slowly at room temperature but not under cryo-conditions of 95 K. The
      structure of the complex with the true substrate obtained by cryo-crystallography
      reveals that indole-3-glycerol phosphate and indole-3-propanol phosphate have
      similar binding modes but different torsion angles. Most importantly, the side
      chain of alphaGlu49 interacts with 3-hydroxyl group of indole-3-glycerol
      phosphate as proposed. The movement of the side chain of alphaGlu49 into an
      extended conformation upon binding the true substrate provides evidence for an
      induced fit mechanism. Our results demonstrate how cryo-crystallography and
      mutagenesis can provide insight into enzyme mechanism.

PMID- 9535828
TI  - Control of human muscle-type carnitine palmitoyltransferase I gene transcription
      by peroxisome proliferator-activated receptor.
AB  - The expression of several genes involved in intra- and extracellular lipid
      metabolism, notably those involved in peroxisomal and mitochondrial beta
      oxidation, is mediated by ligand-activated receptors, collectively referred to as
      peroxisome proliferator-activated receptors (PPARs). To gain more insight into
      the control of expression of carnitine palmitoyltransferase (CPT) genes, which
      are regulated by fatty acids, we have examined the transcriptional regulation of
      the human MCPT I gene. We have cloned by polymerase chain reaction the 5'
      flanking region of this gene and demonstrated its transcriptional activity by
      transfection experiments with the CAT gene as a reporter. We have also shown that
      this is a target gene for the action of PPARs, and we have localized a PPAR
      responsive element upstream of the first exon. These results show that PPAR
      regulates the entry of fatty acids into the mitochondria, which is a crucial step
      in their metabolism, especially in tissues like heart, skeletal muscle and brown
      adipose tissue in which fatty acids are a major source of energy.

PMID- 9535827
TI  - The role of Cdc42 in signal transduction and mating of the budding yeast
      Saccharomyces cerevisiae.
AB  - The small G-protein Cdc42 functions in many eukaryotic signal transduction
      pathways. In the budding yeast Saccharomyces cerevisiae, cells with defective
      Cdc42 fail to induce mating-specific genes in response to mating factor and to
      adopt the proper morphology for conjugation. Here we show that the failure of
      mating factor-induced transcription is largely the indirect result of arrest at a
      specific cell cycle position and/or the accumulation of high levels of the Cln1/2
      Cdc28 kinase, a known repressor of mating factor signal transduction. Cdc42
      defective cells with restored transcriptional induction have a partially restored
      mating ability but are still defective in the morphological response to mating
      factor. These results show that Cdc42 is not required for transduction of the
      mating factor signal per se but that it is essential for proper mating factor
      induced morphogenesis.

PMID- 9535829
TI  - Hydrogen peroxide causes RAD9-dependent cell cycle arrest in G2 in Saccharomyces
      cerevisiae whereas menadione causes G1 arrest independent of RAD9 function.
AB  - This study shows differences at the level of cell cycle arrest between the
      response of yeast cells to hydrogen peroxide and superoxide stress. These include
      both cell cycle phases at which arrest occurs and the involvement of the RAD9
      checkpoint gene. Wild-type and rad9 cells were treated with hydrogen peroxide or
      the superoxide-generating agent menadione. rad9 mutants were up to 100-fold more
      sensitive to hydrogen peroxide but not affected in their resistance to menadione.
      Hydrogen peroxide caused G2-phase arrest, whereas menadione-treated cells
      arrested in G1. G2 arrest, induced by methyl 2-benzimidazil carbamate, increased
      cellular resistance to hydrogen peroxide but not to menadione. G1 arrest mediated
      by alpha-factor caused an increase in survival of wild-type cells treated with
      menadione but not with hydrogen peroxide. A cdc28 mutant arrested in G1 was
      significantly more sensitive to hydrogen peroxide than other cdc mutants arrested
      in later phases, including G2. rad9 cells have normal stationary phase resistance
      to hydrogen peroxide, the ability to adapt to it, glutathione content and
      induction of genes via the stress responsive element. Although rad9-dependent G2
      arrest is important, other rad9-dependent factors may be involved in the
      resistance of cells to hydrogen peroxide since arrest in G2 did not make rad9
      cells fully resistant.

PMID- 9535830
TI  - In vitro cleavage of internally quenched fluorogenic human proparathyroid hormone
      and proparathyroid-related peptide substrates by furin. Generation of a potent
      inhibitor.
AB  - The cleavage of parathyroid hormone (PTH) from its precursor proparathyroid
      hormone (pro-PTH) is accomplished efficiently by the proprotein convertase furin
      (Hendy, G. N., Bennett, H. P. J., Gibbs, B. F., Lazure, C., Day, R., and Seidah,
      N. G. (1995) J. Biol. Chem. 270, 9517-9525). We also showed that a synthetic
      peptide comprising the -6 to +7 sequence of human pro-PTH is appropriately
      cleaved by purified furin in vitro. The human pro-PTH processing site Lys-Ser-Val
      Lys-Lys-Arg differs from the consensus furin site Arg-Xaa-(Lys/Arg)-Arg that is
      represented by Arg-Arg-Leu-Lys-Arg in the cleavage site of pro-PTH-related
      peptide (pro-PTHrP). An earlier study demonstrated that an internally quenched
      fluorogenic substrate bearing an O-aminobenzoyl fluorescent donor at the NH2
      terminus and an acceptor 3-nitrotyrosine near the COOH terminus was appropriately
      cleaved by the convertases furin and PC1 (Jean, F., Basak, A., DiMaio, J.,
      Seidah, N. G., and Lazure, C. (1995) Biochem. J. 307, 689-695). Here, we have
      synthesized a series of internally quenched fluorogenic substrates based upon the
      pro-PTH and pro-PTHrP sequences to determine which residues are important for
      furin cleavage. Purified recombinant furin and PC1 cleaved the human pro-PTH
      internally quenched substrate at the appropriate site in an identical manner to
      that observed with the nonfluorescent peptide. Several substitutions in the P6-P3
      sequence were well tolerated; however, replacement of the Lys at the P6 position
      with Gly and replacement of the P3 Lys by an acidic residue led to markedly
      compromised cleavage by furin. Furin activity was very sensitive to substitution
      in P' positions. Replacement of Ser at P1' with Gly and Val at P2' with Ala
      generated substrates that were less well cleaved. Substitution at the P1'
      position of Val for Ser in conjunction with Ala for Val at P2', as well as a
      single substitution of Lys for Val at P2', generated specific inhibitors of furin
      cleavage. The findings of this study open the way to the rational design of
      inhibitors of furin with therapeutic potential.

PMID- 9535832
TI  - Specific binding of a designed pyrrolidine abasic site analog to multiple DNA
      glycosylases.
AB  - In the base excision DNA repair pathway, DNA glycosylases recognize damaged bases
      in DNA and catalyze their excision through hydrolysis of the N-glycosidic bond.
      Attempts to understand the structural basis for DNA damage recognition by DNA
      glycosylases have been hampered by the short-lived association of these enzymes
      with their DNA substrates. To overcome this problem, we have employed an approach
      involving the design and synthesis of inhibitors that form stable complexes with
      DNA glycosylases, which can then be studied biochemically and structurally. We
      have previously reported that double-stranded DNA containing a pyrrolidine abasic
      site analog (PYR) forms an extremely stable complex with the DNA glycosylase AlkA
      and potently inhibits the reaction catalyzed by the enzyme (Scharer, O. D.,
      Ortholand, J.-Y., Ganesan, A., Ezaz-Nikpay, K., and Verdine, G. L. (1995) J. Am.
      Chem. Soc. 117, 6623-6624). Here we investigate the interaction of this inhibitor
      with a variety of additional DNA glycosylases. With the exception of uracil DNA
      glycosylase all the glycosylases tested bind specifically to PYR-containing
      oligonucleotides. By comparing the interaction of DNA glycosylases with PYR and
      the structurally related tetrahydrofuran abasic site analog, we assess the
      importance of the positively charged ammonium group of the pyrrolidine in binding
      to the active site of these enzymes. Such a general inhibitor of DNA glycosyases
      provides a valuable tool to study stable complexes of these enzymes bound to
      substrate-like molecules.

PMID- 9535831
TI  - Rat and calf thioredoxin reductase are homologous to glutathione reductase with a
      carboxyl-terminal elongation containing a conserved catalytically active
      penultimate selenocysteine residue.
AB  - We have determined the sequence of 23 peptides from bovine thioredoxin reductase
      covering 364 amino acid residues. The result was used to identify a rat cDNA
      clone (2.19 kilobase pairs), which contained an open reading frame of 1496 base
      pairs encoding a protein with 498 residues. The bovine and rat thioredoxin
      reductase sequences revealed a close homology to glutathione reductase including
      the conserved active site sequence (Cys-Val-Asn-Val-Gly-Cys). This also confirmed
      the identity of a previously published putative human thioredoxin reductase cDNA
      clone. Moreover, one peptide of the bovine enzyme contained a selenocysteine
      residue in the motif Gly-Cys-SeCys-Gly (where SeCys represents selenocysteine).
      This motif was conserved at the carboxyl terminus of the rat and human enzymes,
      provided that TGA in the sequence GGC TGC TGA GGT TAA, being identical in both
      cDNA clones, is translated as selenocysteine and that TAA confers termination of
      translation. The 3'-untranslated region of both cDNA clones contained a
      selenocysteine insertion sequence that may form potential stem loop structures
      typical of eukaryotic selenocysteine insertion sequence elements required for the
      decoding of UGA as selenocysteine. Carboxypeptidase Y treatment of bovine
      thioredoxin reductase after reduction by NADPH released selenocysteine from the
      enzyme with a concomitant loss of enzyme activity measured as reduction of
      thioredoxin or 5,5'-dithiobis(2-nitrobenzoic acid). This showed that the carboxyl
      terminal motif was essential for the catalytic activity of the enzyme.

PMID- 9535834
TI  - The molecular mechanism of autoxidation for human oxyhemoglobin. Tilting of the
      distal histidine causes nonequivalent oxidation in the beta chain.
AB  - Human oxyhemoglobin showed a biphasic autoxidation curve containing two rate
      constants, i.e. kf for the fast autoxidation due to the alpha chains, and ks for
      the slow autoxidation of the beta chains, respectively. Consequently, the
      autoxidation of the HbO2 tetramer produces two different curves from the pH
      dependence of kf and ks. The analysis of these curves revealed that the beta
      chain of the HbO2 tetramer does not exhibit any proton-catalyzed autoxidation,
      unlike the alpha chain, where a proton-catalyzed process involving the distal
      histidine residue can play a dominant role in the autoxidation rate. When the
      alpha and beta chains were separated from the HbO2 tetramer, however, each chain
      was oxidized much more rapidly than in the tetrameric parent. Moreover, the
      separated beta chain was recovered completely to strong acid catalysis in its
      autoxidation rate. These new findings lead us to conclude that the formation of
      the alpha1beta1 contact produces in the beta chain a conformational constraint
      whereby the distal histidine at position 63 is tilted away slightly from the
      bound dioxygen, preventing the proton-catalyzed displacement of O-2 by a solvent
      water molecule. The beta chains have thus acquired a delayed autoxidation in the
      HbO2 tetramer.

PMID- 9535833
TI  - Molecular cloning and characterization of the murine staf cDNA encoding a
      transcription activating factor for the selenocysteine tRNA gene in mouse mammary
      gland.
AB  - We have isolated and characterized a cDNA encoding a transcription activating
      factor for the mouse selenocysteine tRNA (tRNAsec) gene from mouse mammary gland.
      The full-length cDNA, designated m-Staf, has a 1878-base pair open reading frame
      encoding 626 amino acids. The predicted amino acid sequence of m-Staf is highly
      homologous to that of Staf, another selenocysteine tRNA gene transcription
      activating factor of Xenopus laevis. Like Staf, m-Staf contains seven tandemly
      repeated zinc fingers and four repeated motifs. Gel shift assays indicated that
      the recombinant m-Staf specifically bound to the activator element region in the
      mouse tRNAsec gene. Transient co-transfection experiments in Drosophila Schneider
      cells, which lack endogenous Staf-like binding activity, showed that m-Staf
      increased the mouse tRNAsec gene transcription about 15-fold, whereas it
      stimulated Pol II-dependent thymidine kinase promoter only 2-fold. Northern blot
      analysis detected the presence of a 3.4-kilobase pair m-Staf transcript, which
      was widely but differentially expressed in various murine tissues. The binding
      activity of m-Staf in mouse mammary gland was undetectable during virgin and
      postlactating periods but increased markedly in parallel with the increase of
      tRNAsec transcript during the periods of pregnancy and lactation, when the gland
      undergoes growth and development. These results indicate that m-Staf is a
      transcriptional activator of the mouse tRNAsec gene and that its binding activity
      in the mammary gland undergoes developmental alterations.

PMID- 9535835
TI  - Analysis of RhoA-binding proteins reveals an interaction domain conserved in
      heterotrimeric G protein beta subunits and the yeast response regulator protein
      Skn7.
AB  - To identify potential RhoA effector proteins, we conducted a two-hybrid screen
      for cDNAs encoding proteins that interact with a Gal4-RhoA.V14 fusion protein. In
      addition to the RhoA effector ROCK-I we identified cDNAs encoding Kinectin, mDia2
      (a p140 mDia-related protein), and the guanine nucleotide exchange factor, mNET1.
      ROCK-I, Kinectin, and mDia2 can bind the wild type forms of both RhoA and Cdc42
      in a GTP-dependent manner in vitro. Comparison of the ROCK-I and Kinectin
      sequences revealed a short region of sequence homology that is both required for
      interaction in the two-hybrid assay and sufficient for weak interaction in vitro.
      Sequences related to the ROCK-I/Kinectin sequence homology are present in
      heterotrimeric G protein beta subunits and in the Saccharomyces cerevisiae Skn7
      protein. We show that beta2 and Skn7 can interact with mammalian RhoA and Cdc42
      and yeast Rho1, both in vivo and in vitro. Functional assays in yeast suggest
      that the Skn7 ROCK-I/Kinectin homology region is required for its function in
      vivo.

PMID- 9535836
TI  - Structure-function analysis of the active sites of complement receptor type 1.
AB  - Two functionally distinct but homologous sites in complement receptor type 1
      (CR1) (CD35) were further characterized by homologous substitution mutagenesis of
      two CR1 derivatives, each containing one site. In both sites, reducing negative
      and/or increasing positive charge augmented interaction with iC3/C3b and C4b,
      supporting a role of ionic forces in the binding reaction. In one case,
      substitution of Asp at the end of complement control protein repeat (CCP) 2 with
      an Asn transformed the protein, with negligible cofactor activity and iC3
      binding, into a mutant with activities similar to native CR1. Consequently, this
      protein, one-fourth the size of CR1, is a therapeutic candidate for a complement
      inhibitor. Another important observation is that the residues between two CCPs
      contribute to activity, probably because they influence positioning of one CCP
      relative to the next. The initial characterization of the third CCP of an active
      site led to identification of three peptides necessary for binding. In line with
      earlier findings for the first two CCPs, interactions with iC3/C3b are similar
      but not identical to those with C4b, implying overlapping but distinct binding
      domains. Moreover, changes in cofactor activity usually, but not always, parallel
      alterations in binding, indicating that these two activities are separable. We
      also mapped epitopes for a blocking and a function enhancing monoclonal antibody.
      Their effects can be explained by epitope location. The first antibody binds near
      functionally important residues. The second may shield inhibitory (negatively
      charged) residues. These results represent a comprehensive analysis of the active
      sites of CR1, which is built of modules found in more than 50 mammalian proteins.

PMID- 9535838
TI  - A region from the medium chain adaptor subunit (mu) recognizes leucine- and
      tyrosine-based sorting signals.
AB  - Tyrosine-based sorting signals in the cytosolic tails of membrane proteins have
      been found to bind directly to the medium chain subunit (mu) of the adaptor
      complexes AP-1 and AP-2. For the leucine-based signals, an interaction with AP-1
      and AP-2 has been reported, but no specific interacting subunit has been
      demonstrated. After searching for molecules interacting with the leucine-based
      sorting signals within the cytosolic tail of the major histocompatibility complex
      class II-associated invariant chain using a phage display approach, we identified
      phage clones with homology to a conserved region of the AP-1 and AP-2 mu chains.
      To investigate the relevance of these findings, we have expressed regions of
      mouse mu1 and mu2 chains on phage gene product III and investigated the binding
      to tail sequences from various transmembrane proteins with known endosomal
      targeting signals. Enzyme-linked immunosorbent binding assays showed that these
      phages specifically recognized peptides containing functional leucine- and
      tyrosine-based sorting signals, suggesting that these regions of the mu1 and mu2
      chains interact with both types of sorting signals.

PMID- 9535837
TI  - Insulin enhances macrophage scavenger receptor-mediated endocytic uptake of
      advanced glycation end products.
AB  - Hyperglycemia accelerates the formation and accumulation of advanced glycation
      end products (AGE) in plasma and tissue, which may cause diabetic vascular
      complications. We recently reported that scavenger receptors expressed by liver
      endothelial cells (LECs) dominantly mediate the endocytic uptake of AGE proteins
      from plasma, suggesting its potential role as an eliminating system for AGE
      proteins in vivo (Smedsrod, B., Melkko, J., Araki, N., Sano, H., and Horiuchi, S.
      (1997) Biochem. J. 322, 567-573). In the present study we examined the effects of
      insulin on macrophage scavenger receptor (MSR)-mediated endocytic uptake of AGE
      proteins. LECs expressing MSR showed an insulin-sensitive increase of endocytic
      uptake of AGE-bovine serum albumin (AGE-BSA). Next, RAW 264.7 cells expressing a
      high amount of MSR were overexpressed with human insulin receptor (HIR). Insulin
      caused a 3.7-fold increase in endocytic uptake of 125I-AGE-BSA by these cells.
      The effect of insulin was inhibited by wortmannin, a phosphatidylinositol-3-OH
      kinase (PI3 kinase) inhibitor. To examine at a molecular level the relationship
      between insulin signal and MSR function, Chinese hamster ovary (CHO) cells
      expressing a negligible level of MSR were cotransfected with both MSR and HIR.
      Insulin caused a 1.7-fold increase in the endocytic degradation of 125I-AGE-BSA
      by these cells, the effect of which was also inhibited by wortmannin and
      LY294002, another PI3 kinase inhibitor. Transfection of CHO cells overexpressing
      MSR with two HIR mutants, a kinase-deficient mutant, and another lacking the
      binding site for insulin receptor substrates (IRS) resulted in disappearance of
      the stimulatory effect of insulin on endocytic uptake of AGE proteins. The
      present results indicate that insulin may accelerate MSR-mediated endocytic
      uptake of AGE proteins through an IRS/PI3 kinase pathway.

PMID- 9535839
TI  - Characterization of a b2delta complex from Escherichia coli ATP synthase.
AB  - The delta subunit of Escherichia coli ATP synthase has been expressed and
      purified, both as the intact polypeptide and as delta', a proteolytic fragment
      composed of residues 1-134. The solution structure of delta' as a five-helix
      bundle has been previously reported (Wilkens, S., Dunn, S. D., Chandler, J.,
      Dahlquist, F. W., and Capaldi, R. A. (1997) Nat. Struct. Biol. 4, 198-201). The
      delta subunit, in conjunction with delta-depleted F1-ATPase, was fully capable of
      reconstituting energy-dependent fluorescence quenching in membrane vesicles that
      had been depleted of F1. A complex of delta with the cytoplasmic domain of the b
      subunit of F0 was demonstrated and characterized by analytical
      ultracentrifugation using bST34-156, a form of the b domain lacking aromatic
      residues. Molecular weight determination by sedimentation equilibrium supported a
      b2delta subunit stoichiometry. The sedimentation coefficient of the complex, 2.1
      S, indicated a frictional ratio of approximately 2, suggesting that delta and the
      b dimer are arranged in an end-to-end rather than side-by-side manner. These
      results indicate the feasibility of the b2delta complex reaching from the
      membrane to the membrane-distal portion of the F1 sector, as required if it is to
      serve as a second stalk.

PMID- 9535840
TI  - Processing of the presequence of the Schizosaccharomyces pombe Rieske iron-sulfur
      protein occurs in a single step and can be converted to two-step processing by
      mutation of a single proline to serine in the presequence.
AB  - The iron-sulfur proteins of the cytochrome bc1 complexes of Schizosaccharomyces
      pombe and Saccharomyces cerevisiae contain the three amino acid motif RX(
      downward arrow)(F/L/I)XX(T/S/G)XXXX (downward arrow) that is typical for proteins
      that are cleaved sequentially in two steps by matrix processing peptidase (MPP)
      and mitochondrial intermediate peptidase (MIP). Despite the presence of this
      recognition sequence the S. pombe iron-sulfur protein is processed only once
      during import into mitochondria, whereas the S. cerevisiae protein is processed
      in two steps. Import of S. pombe iron-sulfur protein in which the putative MIP or
      MPP recognition sites are eliminated by site-directed mutagenesis and import of
      iron-sulfur protein into mitochondria from yeast mutants that lack MIP activity
      indicate that one step processing of the S. pombe iron-sulfur protein is
      independent of those sites and of MIP activity. Sequencing of the mature protein
      obtained after import in vitro and of the endogenous iron-sulfur protein isolated
      from mitochondrial membranes by preparative 2D-electrophoresis shows that MPP
      recognizes a second site in the presequence and processing occurs between
      residues 43 and 44. If proline-20 of the S. pombe presequence is changed into a
      serine, a second cleavage step is induced. Conversely, if serine-24 of the S.
      cerevisiae presequence is changed to a proline, the first cleavage step that is
      normally catalyzed by MPP is blocked, causing precursor iron-sulfur protein to
      accumulate. Together these results indicate that a single amino acid change in
      the presequence is responsible for one-step processing in S. pombe versus two
      step processing in S. cerevisiae.

PMID- 9535841
TI  - Probing the structure of the nicotinic acetylcholine receptor ion channel with
      the uncharged photoactivable compound -3H-diazofluorene.
AB  - The uncharged photoactivable probe 2-[3H]diazofluorene ([3H]DAF) was used to
      examine structural changes in the Torpedo californica nicotinic acetylcholine
      receptor (AChR) ion channel induced by agonists. Photoincorporation of [3H]DAF
      into the AChR consisted of the following two components: a nonspecific component
      consistent with incorporation into residues situated at the lipid-protein
      interface, and a specific component, inhibitable by noncompetitive antagonists
      and localized to the M2 hydrophobic segments of AChR subunits. The nonspecific
      [3H]DAF incorporation was characterized in the M4 segment of each AChR subunit.
      The observed distribution and periodicity of labeled residues reinforce the
      conclusion that the M4 segments are organized as transmembrane alpha-helices with
      a common "face" of each helix in contact with lipid. Within the M2 segments, in
      the absence of agonist [3H]DAF specifically labeled homologous residues betaVal
      261 and deltaVal-269, with incorporation into deltaVal-269 at a 5-fold greater
      efficiency than into betaVal-261. This observation, coupled with the lack of
      detectable incorporation into alpha-M2 including the homologous alphaVal-255,
      indicates that within the resting channel [3H]DAF is bound with its photoreactive
      diazo group oriented toward deltaVal-269. In the presence of agonist, there is an
      approximately 90% reduction in the labeling of betaVal-261 and deltaVal-269
      accompanied by specific incorporation into residues (betaLeu-257, betaAla-258,
      deltaSer-262, and deltaLeu-265) situated 1 or 2 turns of an alpha-helix closer to
      the cytoplasmic end of the M2 segments. The results provide a further
      characterization of agonist-induced rearrangements of the M2 (ion channel) domain
      of the AChR.

PMID- 9535842
TI  - Lamin B phosphorylation by protein kinase calpha and proteolysis during apoptosis
      in human leukemia HL60 cells.
AB  - Protein phosphorylation plays an important role in signal transduction, but its
      involvement in apoptosis still remains unclear. In this report, the p53-null
      human leukemia HL60 cells were used to investigate phosphorylation and
      degradation of lamin B during apoptosis. We found that lamin B was phosphorylated
      within 1 h after addition of the DNA topoisomerase I inhibitor, camptothecin, and
      that lamin B phosphorylation preceded lamin B degradation and DNA fragmentation.
      Using a cell-free system we also found that cytosol from camptothecin-treated
      cells induced lamin B phosphorylation and degradation in isolated nuclei from
      untreated HL60 cells. Lamin B phosphorylation was prevented by the protein kinase
      C (PKC) inhibitor 7-hydroxystaurosporine (UCN-01) but not by the Cdc2 inhibitor,
      flavopiridol. Phosphorylation of lamin B was inhibited by immunodepletion of
      PKCalpha from activated cytosol and was restored by addition of purified
      PKCalpha. PKCalpha activity also increased rapidly as lamin B was phosphorylated
      after initiation of the apoptotic response in HL60 cells. These data suggest that
      lamin B is phosphorylated by PKCalpha and proteolyzed before DNA fragmentation in
      HL60 cells undergoing apoptosis.

PMID- 9535844
TI  - Binding of bacterial peptidoglycan to CD14.
AB  - The hypothesis that soluble peptidoglycan (sPGN, a macrophage-activator from Gram
      positive bacteria) binds to CD14 (a lipopolysaccharide (LPS) receptor) was
      tested. sPGN specifically bound to CD14 in the following three assays: binding of
      soluble 32P-CD14 (sCD14) to agarose-immobilized sPGN, enzyme-linked immunosorbent
      assay, and photoaffinity cross-linking. sCD14 also specifically bound to agarose
      immobilized muramyl dipeptide or GlcNAc-muramyl dipeptide but not to PGN
      pentapeptide. Binding of sCD14 to both sPGN and ReLPS (where ReLPS is LPS from
      Salmonella minnesota Re 595) was competitively inhibited by unlabeled sCD14, 1
      152 N-terminal fragment of sCD14, sPGN, smooth LPS, ReLPS, lipid A, and
      lipoteichoic acid but not by dextran, dextran sulfate, heparin, ribitol teichoic
      acid, or soluble low molecular weight PGN fragments. Binding of sCD14 to sPGN was
      slower than to ReLPS but of higher affinity (KD = 25 nM versus 41 nM). LPS
      binding protein (LBP) increased the binding of sCD14 to sPGN by adding another
      lower affinity KD and another higher Bmax, but for ReLPS, LBP increased the
      affinity of binding by yielding two KD with significantly higher affinity (7.1
      and 27 nM). LBP also enhanced inhibition of sCD14 binding by LPS, ReLPS, and
      lipid A. Binding of sCD14 to both sPGN and ReLPS was inhibited by anti-CD14 MEM
      18 mAb, but other anti-CD14 mAbs showed differential inhibition, suggesting
      conformational binding sites on CD14 for sPGN and LPS, that are partially
      identical and partially different.

PMID- 9535843
TI  - The membrane topology of human transient receptor potential 3 as inferred from
      glycosylation-scanning mutagenesis and epitope immunocytochemistry.
AB  - Transient receptor potential (Trp) proteins form ion channels implicated in the
      calcium entry observed after stimulation of the phospholipase C pathway. Kyte
      Doolittle analysis of the amino acid sequence of Trp proteins identifies seven
      hydrophobic regions (H1-H7) with potential of forming transmembrane segments. A
      limited sequence similarity to voltage-gated calcium channel alpha1 subunits lead
      to the prediction of six transmembrane (TM) segments flanked by intracellular N
      and C termini and a putative pore region between TM5 and TM6. However,
      experimental evidence supporting this model is missing. Using human Trp 3 to test
      Trp topology, we now confirm the intracellular nature of the termini by
      immunocytochemistry. We also demonstrate presence of a unique glycosylation site
      in position 418, which defines one extracellular loop between H2 and H3. After
      removal of this site and insertion of ten separate glycosylation sites, we
      defined two additional extracellular loops between H4 and H5, and H6 and H7. This
      demonstrated the existence of six transmembrane segments formed of H2-H7. Thus,
      the first hydrophobic region of Trp rather than being a transmembrane segment is
      intracellular and available for protein-protein interactions. A site placed in
      the center of the putative pore region was glycosylated, suggesting that this
      region may have been luminal and was reinserted into the membrane at a late stage
      of channel assembly.

PMID- 9535845
TI  - Physical and functional interactions between receptor-like protein-tyrosine
      phosphatase alpha and p59fyn.
AB  - We have examined the in vivo activity of receptor-like protein-tyrosine
      phosphatase alpha (PTPalpha) toward p59(fyn), a widely expressed Src family
      kinase. In a coexpression system, PTPalpha effected a dose-dependent tyrosine
      dephosphorylation and activation of p59(fyn), where maximal dephosphorylation
      correlated with a 5-fold increase in kinase activity. PTPalpha expression
      resulted in increased accessibility of the p59(fyn) SH2 domain, consistent with a
      PTPalpha-mediated dephosphorylation of the regulatory C-terminal tyrosine residue
      of p59(fyn). No p59(fyn) dephosphorylation was observed with an enzymatically
      inactive mutant form of PTPalpha or with another receptor-like PTP, CD45. Many
      enzyme-linked receptors are complexed with their substrates, and we examined
      whether PTPalpha and p59(fyn) underwent association. Reciprocal
      immunoprecipitations and assays detected p59(fyn) and an appropriate kinase
      activity in PTPalpha immunoprecipitates and PTPalpha and PTP activity in p59(fyn)
      immunoprecipitates. No association between CD45 and p59(fyn) was detected in
      similar experiments. The PTPalpha-mediated activation of p59(fyn) is not
      prerequisite for association since wild-type and inactive mutant PTPalpha bound
      equally well to p59(fyn). Endogenous PTPalpha and p59(fyn) were also found in
      association in mouse brain. Together, these results demonstrate a physical and
      functional interaction of PTPalpha and p59(fyn) that may be of importance in
      PTPalpha-initiated signaling events.

PMID- 9535846
TI  - STAT1 is inactivated by a caspase.
AB  - Apoptosis involves the activation of a cascade of interleukin-1beta converting
      enzyme-like proteases (caspases), a group of cysteine proteases related to the
      prototype interleukin-1beta-converting enzyme (caspase-1). These proteases cleave
      specific intracellular targets such as poly(ADP-ribose) polymerase, DNA-dependent
      protein kinase, and nuclear lamins. We show here that apoptosis can be induced by
      double-stranded RNA. The induction of apoptosis by double-stranded RNA and other
      agents leads to the cleavage by a caspase of the signal transducer and activator
      of transcription factor, STAT1 which is pivotal in the signal transduction
      pathways of the interferons and many other cytokines and growth factors. The
      product of this cleavage is no longer able to mediate interferon-activated signal
      transduction and the cleavage event may play a role in regulating the apoptosis
      response itself.

PMID- 9535847
TI  - Mtd, a novel Bcl-2 family member activates apoptosis in the absence of
      heterodimerization with Bcl-2 and Bcl-XL.
AB  - We have identified and characterized Mtd, a novel regulator of apoptosis.
      Sequence analysis revealed that Mtd is a member of the Bcl-2 family of proteins
      containing conserved BH1, BH2, BH3, and BH4 regions and a carboxyl-terminal
      hydrophobic domain. In adult tissues, Mtd mRNA was predominantly detected in the
      brain, liver, and lymphoid tissues, while in the embryo Mtd mRNA was detected in
      the liver, thymus, lung, and intestinal epithelium. Expression of Mtd promoted
      the death of primary sensory neurons, 293T cells and HeLa cells, indicating that
      Mtd is a proapoptotic protein. Unlike all other known death agonists of the Bcl-2
      family, Mtd did not bind significantly to the survival-promoting proteins Bcl-2
      or Bcl-XL. Furthermore, apoptosis induced by Mtd was not inhibited by Bcl-2 or
      Bcl-XL. A Mtd mutant with glutamine substitutions of highly conserved amino acids
      in the BH3 domain retained its ability to promote apoptosis, further indicating
      that Mtd does not promote apoptosis by heterodimerizing with Bcl-2 or Bcl-XL. Mtd
      induced apoptosis was not blocked by broad range synthetic caspase inhibitors z
      VAD-fmk or a viral protein CrmA. Mtd is the first example of a naturally
      occurring Bcl-2 family member that can activate apoptosis independently of
      heterodimerization with survival-promoting Bcl-2 and Bcl-XL.

PMID- 9535848
TI  - Identification of pactolus, an integrin beta subunit-like cell-surface protein
      preferentially expressed by cells of the bone marrow.
AB  - We have sought to develop methodologies to identify genes that are preferentially
      expressed during the differentiation of mast cells from their hematopoietic stem
      cell precursors. By using a modified differential display protocol, we compared a
      subset of transcripts expressed in bone marrow cells differentiated into immature
      mast cells with the exogenous addition of stem cell factor (SCF) or interleukin
      3. One gene was identified that was preferentially expressed in the SCF-derived
      cells and encodes a novel murine integrin beta subunit-like molecule, dubbed
      Pactolus-1 (Pactolus). Two distinct forms of Pactolus mRNA were detected which,
      via alternative splicing, are predicted to encode a membrane-bound form and
      truncated version of the protein. The full-length Pactolus gene product is very
      similar to a number of beta subunit integrin chains, particularly beta2, with the
      notable exceptions of the apparent deletion of the metal-binding site within the
      putative metal ion-dependent adhesion site-like domain of the Pactolus gene
      product and a cytoplasmic domain that shares no obvious homology to similar
      domains of the other beta subunit integrin proteins. Although the Pactolus
      sequence was first identified in immature mast cell samples, screening of murine
      tissues indicated the highest level of Pactolus expression was found in the bone
      marrow, suggesting that the expression of Pactolus is confined to immature and
      maturing bone marrow-derived cells, and that the SCF-derived mast cells are more
      representative of this state than are the interleukin 3-derived mast cells.
      Immunoprecipitation of Pactolus revealed a cell-surface protein with an apparent
      molecular mass of about 95 kDa. Surprisingly, no associating alpha integrin
      subunit could be identified suggesting that either Pactolus does not associate
      with another integrin subunit or the association is too weak to be identified.
      These data suggest that Pactolus represents a gene and gene product related to
      those of the integrin beta subunits but whose function(s) may be quite distinct
      from those of the integrin beta subunits.

PMID- 9535849
TI  - Expression of the UDP-glucuronosyltransferase 1A locus in human colon.
      Identification and characterization of the novel extrahepatic UGT1A8.
AB  - UDP-glucuronosyltransferases (UGT) catalyze the conjugation of lipophilic
      exobiotic and endobiotic compounds, which leads to the excretion of hydrophilic
      glucuronides via bile or urine. By a mechanism of exon sharing, the transcripts
      of individual first exon cassettes located at the 5' end of the human UGT1A locus
      are spliced to exons 2-5, leading to the expression of at least nine individual
      UGT genes. Recently, the tissue-specific expression of the UGT1A locus has been
      demonstrated in extrahepatic tissue, leading to the identification of UGT1A7 and
      UGT1A10 mRNA (Strassburg, C. P., Oldhafer, K., Manns, M. P., and Tukey, R. H.
      (1997) Mol. Pharmacol. 52, 212). However, UGT1A expression has not been defined
      in human colon, which is a metabolically active, external surface organ and a
      common route of drug administration. UGT1A expression was analyzed in 5 colonic,
      16 hepatic, 4 biliary, and 13 gastric human tissue specimens by quantitative
      duplex reverse transcription-polymerase chain reaction and Western blot analysis,
      demonstrating lower UGT1A mRNA in the extrahepatic tissues. The precise analysis
      of unique UGT1A transcripts by exon 1-specific duplex reverse transcription
      polymerase chain reaction revealed the expression of UGT1A1, UGT1A3, UGT1A4,
      UGT1A6, and UGT1A9 in the colon, which are also present in human liver. In
      addition, the expression of extrahepatic UGT1A10 and UGT1A8 was demonstrated.
      UGT1A8 was found to be closely related to gastric UGT1A7 with a 93.8% identity of
      first exon sequences. Expressed UGT1A7 and UGT1A10 protein showed unique
      catalytic activity profiles, while UGT1A8 was not active with the substrates
      tested. The ability of UGT1A10 to glucuronidate estrone represents only the
      second example of a human estrone UGT. The highly related human UGT1A7-1A10
      cluster is expressed in a tissue-specific fashion and underlines the role and
      diversity of physiological glucuronidation at the distal end of the digestive
      tract.

PMID- 9535850
TI  - Differentiation-stimulated activity binds an ETS-like, essential regulatory
      element in the human promyelocytic defensin-1 promoter.
AB  - The human HNP-defensin-1 gene encodes a peptide antibiotic found exclusively in
      neutrophils and is key to elimination of microbes. Expression is a marker for the
      granulocytic lineage and for certain stages of differentiation and is not known
      to be inducible in mature cells under physiological conditions. Low level of
      transcription also occurs in HL-60 promyelocytic leukemia cells and is greatly
      activated upon drug-induced granulocytic maturation and by low doses of retinoic
      acid, in a strictly cell-specific manner (Herwig, S., Su, Q., Ma, Y., and Tempst,
      P. (1996) Blood 87, 350-364). We have analyzed a 10-kilobase pair region,
      upstream of the defensin-1 cap site, for the presence of control elements, and we
      describe a minimal promoter (position -83 to +82) required to drive transcription
      in HL-60 cells in a quasi cell-specific manner. Our data also suggest the
      presence of negative regulatory elements in the -416/-191 region that may further
      contribute to cell specificity in a chromosomal context. The basal promoter
      contains two functionally essential, ETS-like (GGAA core sequence) elements. The
      proximal site (-22/-19) constitutively binds the PU.1 transcription factor in
      vitro and could function, together perhaps with an adjacent TA-rich sequence (
      32/-25), in assembly of a myeloid-restricted, basal transcription factor complex.
      The distal site (-62/-59) interacts in vitro with an unidentified activity,
      distinct from PU.1, ETS-1, PEA3, and ELK-1 (factors with definite binding site
      similarities), and is greatly stimulated by phosphorylation during granulocytic
      differentiation of HL-60 cells. Identification of this protein will be important
      to resolve the molecular mechanisms controlling temporal, granulocytic restricted
      gene expression.

PMID- 9535851
TI  - Type I phosphatidylinositol-4-phosphate 5-kinases. Cloning of the third isoform
      and deletion/substitution analysis of members of this novel lipid kinase family.
AB  - Type I phosphatidylinositol 4-phosphate (PtdIns(4)P) 5-kinases (PIP5K) catalyze
      the synthesis of phosphatidylinositol 4, 5-bisphosphate, an essential lipid
      molecule in various cellular processes. Here, we report the cloning of the third
      member (PIP5Kgamma) and the characterization of members of the type I PIP5K
      family. Type I PIP5Kgamma has two alternative splicing forms, migrating at 87 and
      90 kDa on SDS-polyacrylamide gel electrophoresis. The amino acid sequence of the
      central portion of this isoform shows approximately 80% identity with those of
      the alpha and beta isoforms. Northern blot analysis revealed that the gamma
      isoform is highly expressed in the brain, lung, and kidneys. Among three
      isoforms, the beta isoform has the greatest Vmax value for the PtdIns(4)P kinase
      activity and the gamma isoform is most markedly stimulated by phosphatidic acid.
      By analyzing deletion mutants of the three isoforms, the minimal kinase core
      sequence of these isoforms were determined as an approximately 380-amino acid
      region. In addition, carboxyl-terminal regions of the beta and gamma isoforms
      were found to confer the greatest Vmax value and the highest phosphatidic acid
      sensitivity, respectively. It was also discovered that lysine 138 in the putative
      ATP binding motif of the alpha isoform is essential for the PtdIns(4)P kinase
      activity. As was the case with the alpha isoform reported previously (Shibasaki,
      Y., Ishihara, H., Kizuki, N., Asano, T., Oka, Y., Yazaki, Y. (1997) J. Biol.
      Chem. 272, 7578-7581), overexpression of either the beta or the gamma isoform
      induced an increase in short actin fibers and a decrease in actin stress fibers
      in COS7 cells. Surprisingly, a kinase-deficient substitution mutant also induced
      an abnormal actin polymerization, suggesting a role of PIP5Ks via structural
      interactions with other molecules.

PMID- 9535852
TI  - Transcriptional activation of heat shock factor HSF1 probed by phosphopeptide
      analysis of factor 32P-labeled in vivo.
AB  - Mapping of tryptic phosphopeptides of heat shock factor 1 (HSF1) from non
      stressed or moderately heat-stressed HeLa cells, labeled in vivo by
      [32P]orthophosphate, revealed four major phosphopeptides A to D. Heat stress
      drastically increased phosphopeptide signals. To identify target peptides and
      amino acids and to correlate phosphorylation and transactivation function,
      phosphopeptide maps were produced of LexA-human HSF1 chimeras and mutant
      derivatives thereof, and transactivation activities of original and mutant
      chimeras were compared. LexA-HSF1 chimeras were previously shown to be regulated
      identically to HSF1, except that they transactivate promoters with LexA-binding
      sites instead of hsp promoters. The patterns of phosphopeptides of LexA-HSF1 and
      endogenous HSF1 were similar. Analysis of single residue substitutions suggested
      that phosphopeptide C is peptide VKEEPPSPPQSPR (297-309) phosphorylated on Ser
      307 but not Ser-303. Substitution of Ser-307 but not Ser-303 caused deregulation
      of factor activity. Mapping of several constitutively active chimeras associated
      unphosphorylated peptide C with the transcriptionally active HSF1 conformation,
      suggesting that dephosphorylation of this peptide (at Ser-307) may either be an
      integral step in the activation process or serve to maintain the active
      conformation of HSF1. Exploiting this correlation, indirect evidence was obtained
      that activation domains of HSF1 interact with the distantly located regulatory
      domain to maintain the factor in an inactive state.

PMID- 9535853
TI  - A common mechanism for the interaction of nitric oxide with the oxidized
      binuclear centre and oxygen intermediates of cytochrome c oxidase.
AB  - The reactions of nitric oxide (NO) with fully oxidized cytochrome c oxidase (O)
      and the intermediates P and F have been investigated by optical spectroscopy,
      using both static and kinetic methods. The reaction of NO with O leads to a rapid
      (approximately 100 s-1) electron ejection from the binuclear center to cytochrome
      a and CuA. The reaction with the intermediates P and F leads to the depletion of
      these species in slower reactions, yielding the fully oxidized enzyme. The
      fastest optical change, however, takes place within the dead time of the stopped
      flow apparatus (approximately 1 ms), and corresponds to the formation of the F
      intermediate (580 nm) upon reaction of NO with a species that we postulate is at
      the peroxide oxidation level. This species can be formulated as either Fe5+ = O
      CuB2+ or Fe4+ = O CuB3+, and it is spectrally distinct from the P intermediate
      (607 nm). All of these reactions have been rationalized through a mechanism in
      which NO reacts with CuB2+, generating the nitrosonium species CuB1+ NO+, which
      upon hydration yields nitrous acid and CuB1+. This is followed by redox
      equilibration of CuB with Fea/CuA or Fea3 (in which Fea and Fea3 are the iron
      centers of cytochromes a and a3, respectively). In agreement with this
      hypothesis, our results indicate that nitrite is rapidly formed within the
      binuclear center following the addition of NO to the three species tested (O, P,
      and F). This work suggests that nitrosylation at CuB2+ instead of at Fea32+ is a
      key event in the fast inhibition of cytochrome c oxidase by NO.

PMID- 9535854
TI  - Glomerular basement membrane. Identification of a novel disulfide-cross-linked
      network of alpha3, alpha4, and alpha5 chains of type IV collagen and its
      implications for the pathogenesis of Alport syndrome.
AB  - Glomerular basement membrane (GBM) plays a crucial function in the
      ultrafiltration of blood plasma by the kidney. This function is impaired in
      Alport syndrome, a hereditary disorder that is caused by mutations in the gene
      encoding type IV collagen, but it is not known how the mutations lead to a
      defective GBM. In the present study, the supramolecular organization of type IV
      collagen of GBM was investigated. This was accomplished by using pseudolysin (EC
      3.4.24.26) digestion to excise truncated triple-helical protomers for structural
      studies. Two distinct sets of truncated protomers were solubilized, one at 4
      degrees C and the other at 25 degrees C, and their chain composition was
      determined by use of monoclonal antibodies. The 4 degrees C protomers comprise
      the alpha1(IV) and alpha2(IV) chains, whereas the 25 degrees C protomers
      comprised mainly alpha3(IV), alpha4(IV), and alpha5(IV) chains along with some
      alpha1(IV) and alpha2(IV) chains. The structure of the 25 degrees C protomers was
      examined by electron microscopy and was found to be characterized by a network
      containing loops and supercoiled triple helices, which are stabilized by
      disulfide cross-links between alpha3(IV), alpha4(IV), and alpha5(IV) chains.
      These results establish a conceptual framework to explain several features of the
      GBM abnormalities of Alport syndrome. In particular, the alpha3(IV).
      alpha4(IV).alpha5(IV) network, involving a covalent linkage between these chains,
      suggests a molecular basis for the conundrum in which mutations in the gene
      encoding the alpha5(IV) chain cause defective assembly of not only alpha5(IV)
      chain but also the alpha3(IV) and alpha4(IV) chains in the GBM of patients with
      Alport syndrome.

PMID- 9535855
TI  - Interaction of Rac1 with GTPase-activating proteins and putative effectors. A
      comparison with Cdc42 and RhoA.
AB  - The intrinsic GTPase activity of the Rho family GTP-binding protein Rac1 is
      drastically stimulated upon interaction with its GTPase-activating proteins
      (GAPs) and is significantly inhibited when coupled to certain effector targets
      such as the p21-activated kinases (PAKs) and IQGAPs. Here we have characterized
      the interaction of Rac1 with a panel of mammalian GAPs and putative effectors by
      measuring the kinetic and binding parameters involved and made comparisons with
      similar interactions for Cdc42 and RhoA. In contrast with Cdc42 (for which the
      GAP domain of p50RhoGAP is 50-fold more efficient than those of p190, Bcr, and
      3BP-1) and with RhoA (toward which only p50RhoGAP and p190 displayed high
      efficiencies), the catalytic efficiencies (Kcat/Km) of the GAP domains of
      p50RhoGAP, p190, Bcr, and 3BP-1 on Rac1 are found to be comparable in a range
      between 0.9 and 2.6 min-1 microM-1. However, similar to the cases of Cdc42 and
      RhoA, the Km values of the GAP domains on Rac1 compare well to the binding
      affinity to the guanylyl imidodiphosphate-bound Rac1, which ranges from 10.5 to
      40.5 microM, suggesting a rapid equilibrium reaction mechanism. The dissociation
      constants of the p21-binding domains of PAK1, PAK2, and the RasGAP-related domain
      of IQGAP1, which all cause significant reduction of the intrinsic rate of GTP
      hydrolysis upon binding to Rac1-GTP, are found to be 0.71, 0.26, and 2.13 microM
      for Rac1-GTP, compared with that determined for Cdc42-GTP at 2.9, 20.5, and 0.39
      microM, respectively, under similar conditions. These results suggest that
      p50RhoGAP, p190, Bcr, and 3BP-1 are all capable of acting as a negative regulator
      for Rac1-mediated signaling, and that, although PAK1 and IQGAP1 can couple
      tightly with both Rac1 and Cdc42, PAK2 is likely to be a specific effector for
      Rac1 instead of Cdc42.

PMID- 9535856
TI  - Site-directed mutagenesis of conserved aspartates, glutamates and arginines in
      the active site region of Escherichia coli DNA topoisomerase I.
AB  - To catalyze relaxation of supercoiled DNA, DNA topoisomerases form a covalent
      enzyme-DNA intermediate via nucleophilic attack of a tyrosine hydroxyl group on
      the DNA phosphodiester backbone bond during the step of DNA cleavage. Strand
      passage then takes place to change the linking number. This is followed by DNA
      religation during which the displaced DNA hydroxyl group attacks the
      phosphotyrosine linkage to reform the DNA phosphodiester bond. Mg(II) is required
      for the relaxation activity of type IA and type II DNA topoisomerases. A number
      of conserved amino acids with acidic and basic side chains are present near Tyr
      319 in the active site of the crystal structure of the 67-kDa N-terminal fragment
      of Escherichia coli DNA topoisomerase I. Their roles in enzyme catalysis were
      investigated by site-directed mutation to alanine. Mutation of Arg-136 abolished
      all the enzyme relaxation activity even though DNA cleavage activity was
      retained. The Glu-9, Asp-111, Asp-113, Glu-115, and Arg-321 mutants had partial
      loss of relaxation activity in vitro. All the mutants failed to complement
      chromosomal topA mutation in E. coli AS17 at 42 degreesC, possibly accounting for
      the conservation of these residues in evolution.

PMID- 9535857
TI  - Subcellular redistribution is involved in acute regulation of the brush border
      Na+/H+ exchanger isoform 3 in human colon adenocarcinoma cell line Caco-2.
      Protein kinase C-mediated inhibition of the exchanger.
AB  - Na+/H+ exchanger isoform 3 (NHE3), an epithelial brush border isoform of the
      Na+/H+ exchanger gene family, plays an important role in reabsorption of Na+ in
      the small intestine, the colon, and the kidney. In several cell types, phorbol 12
      myristate 13-acetate (PMA) acutely inhibits NHE3 activity by changes in Vmax, but
      the mechanism of this inhibition is unknown. We investigated the role of
      subcellular redistribution of NHE3 in the PMA-induced inhibition of endogenous
      brush border NHE3 in a model human colon adenocarcinoma cell line, Caco-2.
      Subcellular localization of NHE3 was examined by confocal morphometric analysis
      complemented with cell surface biotinylation and compared with NHE3 activity
      evaluated by fluorometric measurement of intracellular pH. PMA inhibited NHE3
      activity by 28% (p < 0.01), which was associated with a decrease of the ratio of
      the brush border/subapical cytoplasmic compartment of NHE3 from approximately 4.3
      to approximately 2.4. This translocation resulted in 10-15% of the total cell
      NHE3 being shifted from the brush border pool to the cytoplasmic pool. These
      effects were mediated by protein kinase C, since they were blocked by the protein
      kinase C inhibitor H7. We conclude that inhibition of NHE3 by protein kinase C in
      Caco-2 cells involves redistribution of the exchanger from brush border into a
      subapical cytoplasmic compartment, and that this mechanism contributes
      approximately 50% to the overall protein kinase C-induced inhibition of the
      exchanger.

PMID- 9535858
TI  - Activation of NF-kappaB is involved in the survival of osteoclasts promoted by
      interleukin-1.
AB  - We previously reported that interleukin-1 (IL-1) promoted the survival of murine
      osteoclast-like cells (OCLs) formed in vitro and activated a transcription
      factor, NF-kappaB, of OCLs. The present study examined whether the activation of
      NF-kappaB is directly involved in the survival of OCLs promoted by IL-1. The
      expression of IL-1 type I receptor mRNA in OCLs was detected by the polymerase
      chain reaction amplification of reverse-transcribed mRNA. An electrophoretic
      mobility shift assay showed that IL-1 transiently activated NF-kappaB in the
      nuclei of the OCLs, and the maximal activation occurred at 30 min. The
      degradation of IkappaBalpha coincided with the activation of NF-kappaB in the
      OCLs. The immunocytochemical study revealed that p65, a subunit of NF-kappaB, was
      translocated from the cytoplasm into almost all of the nuclei of the OCLs within
      30 min after IL-1 stimulation. The purified OCLs spontaneously died via
      apoptosis, and IL-1 promoted the survival of OCLs by preventing their apoptosis.
      The pretreatment of purified OCLs with proteasome inhibitors suppressed the IL-1
      induced activation of NF-kappaB and prevented the survival of OCLs supported by
      IL-1. When OCLs were pretreated with antisense oligodeoxynucleotides to p65 and
      p50 of NF-kappaB, the expression of respective mRNAs by OCLs was suppressed, and
      the IL-1-induced survival of OCLs was concomitantly inhibited. These results
      indicate that IL-1 promotes the survival of osteoclasts through the activation of
      NF-kappaB.

PMID- 9535859
TI  - cis and trans sites of the TOM complex of mitochondria in unfolding and initial
      translocation of preproteins.
AB  - Translocation of preproteins across the mitochondrial outer membrane is mediated
      by the TOM complex. Our previous studies led to the concept of two preprotein
      binding sites acting in series, the surface-exposed cis site and the trans site
      exposed to the intermembrane space. We report here that preproteins are bound to
      the cis site in a labile fashion even at low ionic strength, whereas
      intermediates arrested at the trans site remained firmly bound at higher salt
      concentration. The stability of the trans site intermediate results from
      interactions of both the presequence and unfolded parts of the mature part of the
      preprotein with the TOM complex. Binding to the trans site proceeded at rates
      comparable with those of unfolding of the mature domain and appeared to be
      kinetically limited by the unfolding reaction. Efficient binding to the trans
      site and unfolding were observed with both outer membrane vesicles and intact
      mitochondria whose membrane potential, DeltaPsi, was dissipated. Upon re
      establishing DeltaPsi, trans site-bound preprotein resumed translocation into the
      matrix. The rates of unfolding and binding to the trans site were the same as
      those for translocation into intact energized mitochondria. We conclude that
      preprotein unfolding in intact mitochondria can take place without the
      involvement of the translocation machinery of the inner membrane and, in
      particular, the matrix Hsp70 chaperone. Further, preprotein unfolding at the
      outer membrane can be a rate-limiting step for formation of the trans site
      intermediate and for the entire translocation reaction.

PMID- 9535860
TI  - Phosphorylation of the catalyic alpha-subunit constitutes a triggering signal for
      Na+,K+-ATPase endocytosis.
AB  - Inhibition of Na+,K+-ATPase activity by dopamine is an important mechanism by
      which renal tubules modulate urine sodium excretion during a high salt diet.
      However, the molecular mechanisms of this regulation are not clearly understood.
      Inhibition of Na+,K+-ATPase activity in response to dopamine is associated with
      endocytosis of its alpha- and beta-subunits, an effect that is protein kinase C
      dependent. In this study we used isolated proximal tubule cells and a cell line
      derived from opossum kidney and demonstrate that dopamine-induced endocytosis of
      Na+,K+-ATPase and inhibition of its activity were accompanied by phosphorylation
      of the alpha-subunit. Inhibition of both the enzyme activity and its
      phosphorylation were blocked by the protein kinase C inhibitor
      bisindolylmaleimide. The early time dependence of these processes suggests a
      causal link between phosphorylation and inhibition of enzyme activity. However,
      after 10 min of dopamine incubation, the alpha-subunit was no longer
      phosphorylated, whereas enzyme activity remained inhibited due to its removal
      from the plasma membrane. Dephosphorylation occurred in the late endosomal
      compartment. To further examine whether phosphorylation was a prerequisite for
      subunit endocytosis, we used the opossum kidney cell line transfected with the
      rodent alpha-subunit cDNA. Treatment of this cell line with dopamine resulted in
      phosphorylation and endocytosis of the alpha-subunit with a concomitant decrease
      in Na+,K+-ATPase activity. In contrast, none of these effects were observed in
      cells transfected with the rodent alpha-subunit that lacks the putative protein
      kinase C-phosphorylation sites (Ser11 and Ser18). Our results support the
      hypothesis that protein kinase C-dependent phosphorylation of the alpha-subunit
      is essential for Na+,K+-ATPase endocytosis and that both events are responsible
      for the decreased enzyme activity in response to dopamine.

PMID- 9535861
TI  - Enzymes catalyzing ubiquitination and proteolytic processing of the p105
      precursor of nuclear factor kappaB1.
AB  - Nuclear factor kappaB1 (NF-kappaB) is a heterodimeric complex that regulates
      transcription of many genes involved in immune and inflammatory responses. Its 50
      kDa subunit (p50) is generated by the ubiquitin-proteasome pathway from a 105-kDa
      precursor (p105). We have reconstituted this proteolytic process in HeLa cell
      extracts and purified the responsible enzymes. Ubiquitination of p105 requires
      E1, and either of two types of E2s, E2-25K (for which p105 is the first proven
      substrate) or a member of the UBCH5 (UBC4) family. It also requires a new E3 of
      50 kDa, which we call E3kappaB. This set of enzymes differs from the E2s and E3
      reported by others to catalyze p105 ubiquitination in reticulocytes. The
      ubiquitinating enzymes purified here, together with 26S proteasomes, allowed
      formation of p50. Thus, the 26S proteasome provides all the proteolytic
      activities necessary for p105 processing. Interestingly, in the reconstituted
      system, as observed in cells, the C-terminally truncated form of p105, p97, was
      processed into p50 more efficiently than normal p105, even when both species were
      ubiquitinated to a similar extent. Therefore, some additional mechanism involving
      the C-terminal region of p105 influences the proteolytic processing of the
      ubiquitinated precursor.

PMID- 9535862
TI  - Interference between progesterone and dioxin signal transduction pathways.
      Different mechanisms are involved in repression by the progesterone receptor A
      and B isoforms.
AB  - Interactions between transcription factors are an important means of regulating
      gene transcription, leading to modifications in the pattern of gene expression
      and cell fate. In this study, we report that the progesterone receptor (PR) can
      strongly interfere with transactivation mediated by the arylhydrocarbon receptor
      (AhR) in T47D breast cancer cells. This interference was not only demonstrated by
      induction of a transfected dioxin-responsive reporter plasmid but also on the AhR
      mediated up-regulation of the endogenous cytochrome P450-1A1 activity. The
      interference was not mutual, as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the
      most potent activator of the AhR, did not inhibit progestin-induced promoter
      activity. When the isoforms of the human PR, hPR-A and hPR-B, were expressed
      separately in HepG-2 hepatocarcinoma cells, both negatively interfered with the
      AhR signaling, indicating that the effect is not restricted to T47D cells. In
      addition, results obtained from studies with both antiprogestins and mutant
      receptors indicate differences in the underlying molecular mechanisms of
      repression for both PR isoforms. The suppression by hPR-A does not require
      additional gene expression or a full transcriptional competent conformation of
      the receptor. For the repressive effects of hPR-B, however, additional gene
      expression seems to be involved, as only the agonist-bound, wild-type hPR-B could
      clearly repress the TCDD-induced response. In conclusion, these studies highlight
      different mechanisms of repression for the progesterone receptor isoforms on the
      AhR-mediated trans-activation and underscore the importance of interactions
      between transcription factors of different families in the regulation of gene
      transcription.

PMID- 9535863
TI  - A modular DNA carrier protein based on the structure of diphtheria toxin mediates
      target cell-specific gene delivery.
AB  - Modular fusion proteins that combine distinct functions required for cell type
      specific uptake and intracellular delivery of DNA present an attractive approach
      for the development of self-assembling vectors for targeted gene delivery. Here,
      we describe a novel DNA carrier protein termed GD5 that mimics the structure of
      the bacterial diphtheria toxin (DT) and facilitates target cell-specific gene
      transfer via receptor-mediated endocytosis. GD5 carries at the N terminus the DNA
      binding domain of the yeast transcription factor Gal4, which is connected to a C
      terminal antibody fragment specific for the tumor-associated ErbB2 antigen via an
      internal DT translocation domain as an endosome escape activity. Bacterially
      expressed GD5 protein specifically bound to ErbB2-expressing cells and formed
      protein-DNA complexes with a luciferase reporter gene construct. These complexes,
      after compensation of excess negative charge with poly-L-lysine, served as a
      specific transfection vector for ErbB2-expressing cells. Inhibitors of endosomal
      acidification drastically reduced GD5-mediated transfection, indicating that the
      DT translocation domain of GD5, similar to the parental toxin, is strictly
      dependent on the transit through an acidic environment. Our results suggest that
      fusion proteins that employ the natural endosome escape mechanism of bacterial
      toxins might aid in the development of efficient nonviral vectors for
      applications in gene therapy.

PMID- 9535864
TI  - Involvement of flap endonuclease 1 in base excision DNA repair.
AB  - Base excision repair can proceed in either one of two alternative pathways: a DNA
      polymerase beta-dependent pathway and a proliferating cell nuclear antigen (PCNA)
      dependent pathway. Excision of an apurinic/apyrimidinic (AP) site by cutting the
      phosphate backbone on its 3' side following incision at its 5' side by AP
      endonuclease is a prerequisite to completion of these repair pathways. Using a
      reconstituted system with the proteins derived from Xenopus laevis, we found that
      flap endonuclease 1 (FEN1) was a factor responsible for the excision of a 5'
      incised AP site in the PCNA-dependent pathway. In this pathway, DNA synthesis was
      not required for the action of FEN1 in the presence of PCNA and a replication
      factor C-containing fraction. The polymerase beta-dependent pathway could also
      use FEN1 for excision of the synthetic AP sites, which were not susceptible to
      beta-elimination. In this pathway, FEN1 was functional without PCNA and
      replication factor C but required the DNA synthesis, which led to a flap
      structure formation.

PMID- 9535865
TI  - The assembly system for the lipopolysaccharide R2 core-type of Escherichia coli
      is a hybrid of those found in Escherichia coli K-12 and Salmonella enterica.
      Structure and function of the R2 WaaK and WaaL homologs.
AB  - In Escherichia coli F632, the 14-kilobase pair chromosomal region located between
      waaC (formerly rfaC) and waaA (kdtA) contains genes encoding enzymes required for
      the synthesis of the type R2 core oligosaccharide portion of lipopolysaccharide.
      Ten of the 13 open reading frames encode predicted products sharing greater than
      90% total similarity with homologs in E. coli K-12. However, the products of waaK
      (rfaK) and waaL (rfaL) each resemble homologs in Salmonella enterica serovar
      Typhimurium but share little similarity with E. coli K-12. The F632 WaaK and WaaL
      proteins therefore define differences between the type R2 and K-12 outer core
      oligosaccharides of E. coli lipopolysaccharides. Based on the chemical structure
      of the core oligosaccharide of an E. coli F632 waaK::aacC1 mutant and in vitro
      glycosyltransferase analyses, waaK encodes UDP-N-acetylglucosamine:(glucose)
      lipopolysaccharide alpha1, 2-N-acetylglucosaminyltransferase. The WaaK enzyme
      adds a terminal GlcNAc side branch substituent that is crucial for the
      recognition of core oligosaccharide acceptor by the O-polysaccharide ligase,
      WaaL. Results of complementation analyses of E. coli K-12 and F632 waaL mutants
      suggest that structural differences between the WaaL proteins play a role in
      recognition of, and interaction with, terminal lipopolysaccharide core moieties.

PMID- 9535866
TI  - Studies of the cytochrome subunits of menaquinone:cytochrome c reductase (bc
      complex) of Bacillus subtilis. Evidence for the covalent attachment of heme to
      the cytochrome b subunit.
AB  - The menaquinone:cytochrome c reductase, or bc complex, of Bacillus subtilis
      belongs to a third class of bc-type complex, distinct from the bc1 and b6f
      classes. Using a mutagenesis approach, we demonstrate that the cytochrome b
      (QcrB) and c (QcrC) subunits of the complex give rise to bands at 22 and 29 kDa,
      respectively, after denaturing electrophoresis; that both subunits are required
      for proper complex assembly and/or stability; and that both subunits retain one
      heme molecule under denaturing conditions. This unusual property of a b-type
      cytochrome was investigated further. We present evidence for the existence of a
      covalent linkage between the polypeptide and heme bH and of an important role for
      Cys43 in binding of heme bH. It is proposed that heme is also covalently attached
      to the cytochrome b subunit of b6f complexes of chloroplasts and cyanobacteria.

PMID- 9535867
TI  - Coordinated regulation of the tyrosine phosphorylation of Cbl by Fyn and Syk
      tyrosine kinases.
AB  - Cross-linking of the T cell antigen receptor (TCR)-CD3 complex induces rapid
      tyrosine phosphorylation and activation of Src (Lck and Fyn) and Syk (Syk and Zap
      70) family protein tyrosine kinases (PTKs) which, in turn, phosphorylate multiple
      intracellular substrates. Cbl is a prominent PTK substrate suggesting a pivotal
      role for it in early signal transduction events. However, the regulation of Cbl
      function and tyrosine phosphorylation in T cells by upstream PTKs remains poorly
      understood. In the present study, we used genetic and biochemical approaches to
      demonstrate that Cbl directly interacts with Syk and Fyn via its N-terminal and C
      terminal regions, respectively. Tyr-316 of Syk was required for the interaction
      with Cbl as well as for the maximal tyrosine phosphorylation of Cbl. However,
      both wild-type Syk and Y316F-mutated Syk phosphorylated equally well the C
      terminal fragment of Cbl in vivo, suggesting the existence of an alternative, N
      terminus-independent mechanism for the Syk-induced tyrosine phosphorylation of
      Cbl. This mechanism appears to involve Fyn, since, in addition to its association
      with the C-terminal region of Cbl, Fyn also associated with Syk and enhanced the
      Syk-induced tyrosine phosphorylation of Cbl. These findings implicate Fyn as an
      adaptor protein that facilitates the interaction between Syk and Cbl, and suggest
      that Src and Syk family PTKs coordinately regulate the tyrosine phosphorylation
      of Cbl.

PMID- 9535868
TI  - The intracellular location of NADH:cytochrome b5 reductase modulates the
      cytotoxicity of the mitomycins to Chinese hamster ovary cells.
AB  - NADH:cytochrome b5 reductase activates the mitomycins to alkylating intermediates
      in vitro. To investigate the intracellular role of this enzyme in mitomycin
      bioactivation, Chinese hamster ovary cell transfectants overexpressing rat
      NADH:cytochrome b5 reductase were generated. An NADH:cytochrome b5 reductase
      transfected clone expressed 9-fold more enzyme than did parental cells; the
      levels of other mitomycin-activating oxidoreductases were unchanged. Although
      this enzyme activates the mitomycins in vitro, its overexpression in living cells
      caused decreases in sensitivity to mitomycin C in air and decreases in
      sensitivity to porfiromycin under both air and hypoxia. Mitomycin C cytotoxicity
      under hypoxia was similar to parental cells. Because NADH:cytochrome b5 reductase
      resides predominantly in the mitochondria of these cells, this enzyme may
      sequester these drugs in this compartment, thereby decreasing nuclear DNA
      alkylations and reducing cytotoxicity. A cytosolic form of NADH:cytochrome b5
      reductase was generated. Transfectants expressing the cytosolic enzyme were
      restored to parental line sensitivity to both mitomycin C and porfiromycin in air
      with marked increases in drug sensitivity under hypoxia. The results implicate
      NADH:cytochrome b5 reductase in the differential bioactivation of the mitomycins
      and indicate that the subcellular site of drug activation can have complex
      effects on drug cytotoxicity.

PMID- 9535869
TI  - N5-(1-Imino-3-butenyl)-L-ornithine. A neuronal isoform selective mechanism-based
      inactivator of nitric oxide synthase.
AB  - Nitric oxide synthase (NOS) catalyzes the NADPH- and O2-dependent conversion of L
      arginine to nitric oxide (NO) and citrulline; three isoforms, the neuronal
      (nNOS), endothelial, and inducible, have been identified. Because overproduction
      of NO is known to contribute to several pathophysiological conditions, NOS
      inhibitors are of interest as potential therapeutic agents. Inhibitors that are
      potent, mechanism-based, and relatively selective for the NOS isoform causing
      pathology are of particular interest. In the present studies we report that vinyl
      L-NIO (N5-(1-imino-3-butenyl)-L-ornithine; L-VNIO) binds to and inhibits nNOS in
      competition with L-arginine (Ki = 100 nM); binding is accompanied by a type I
      optical difference spectrum consistent with binding near the heme cofactor
      without interaction as a sixth axial heme ligand. Such binding is fully
      reversible. However, in the presence of NADPH and O2, L-VNIO irreversibly
      inactivates nNOS (kinact = 0.078 min-1; KI = 90 nM); inactivation is
      Ca2+/calmodulin-dependent. The cytochrome c reduction activity of the enzyme is
      not affected by such treatment, but the L-arginine-independent NADPH oxidase
      activity of nNOS is lost in parallel with the overall activity. Spectral analyses
      establish that the nNOS heme cofactor is lost or modified by L-VNIO-mediated
      mechanism-based inactivation of the enzyme. The inducible isoform of NOS is not
      inactivated by L-VNIO, and the endothelial isoform requires 20-fold higher
      concentrations to attain approximately 75% of the rate of inactivation seen with
      nNOS. Among the NOS inactivating L-arginine derivatives, L-VNIO is the most
      potent and nNOS-selective reported to date.

PMID- 9535870
TI  - Calcium-dependent epidermal growth factor receptor transactivation mediates the
      angiotensin II-induced mitogen-activated protein kinase activation in vascular
      smooth muscle cells.
AB  - We have recently reported that angiotensin II (Ang II)-induced mitogen-activated
      protein kinase (MAPK) activation is mainly mediated by Ca2+-dependent activation
      of a protein tyrosine kinase through Gq-coupled Ang II type 1 receptor in
      cultured rat vascular smooth muscle cells (VSMC). In the present study, we found
      Ang II rapidly induced the tyrosine phosphorylation of the epidermal growth
      factor (EGF) receptor and its association with Shc and Grb2. These reactions were
      inhibited by the EGF receptor kinase inhibitor, AG1478. The Ang II-induced
      phosphorylation of the EGF receptor was mimicked by a Ca2+ ionophore and
      completely inhibited by an intracellular Ca2+ chelator. Thus, AG1478 abolished
      the MAPK activation induced by Ang II, a Ca2+ ionophore as well as EGF but not by
      a phorbol ester or platelet-derived growth factor-BB in the VSMC. Moreover, Ang
      II induced association of EGF receptor with catalytically active c-Src. This
      reaction was not affected by AG1478. These data indicate that Ang II induces Ca2+
      dependent transactivation of the EGF receptor which serves as a scaffold for pre
      activated c-Src and for downstream adaptors, leading to MAPK activation in VSMC.

PMID- 9535871
TI  - Degradation versus aggregation of misfolded maltose-binding protein in the
      periplasm of Escherichia coli.
AB  - The periplasmic fates of misfolded MalE31, a defective folding mutant of the
      maltose-binding protein, were determined by manipulating two cellular activities
      affecting the protein folding pathway in host cells: (i) the malEp promoter
      activity, which is controlled by the transcriptional activator MalT, and (ii) the
      DegP and Protease III periplasmic proteolytic activity. At a low level of
      expression, the degradation of misfolded MalE31 was partially impaired in cells
      lacking DegP or Protease III. At a high level of expression, misfolded MalE31
      rapidly formed periplasmic inclusion bodies and thus escaped degradation.
      However, the manipulated host cell activities did not enhance the production of
      periplasmic, soluble MalE31. A kinetic competition between folding, aggregation,
      and degradation is proposed as a general model for the biogenesis of periplasmic
      proteins.

PMID- 9535872
TI  - Nitric oxide trapping of tyrosyl radicals generated during prostaglandin
      endoperoxide synthase turnover. Detection of the radical derivative of tyrosine
      385.
AB  - Tyrosyl radicals have been detected during turnover of prostaglandin endoperoxide
      H synthase (PGHS), and they are speculated to participate in cyclooxygenase
      catalysis. Spectroscopic approaches to elucidate the identity of the radicals
      have not been definitive, so we have attempted to trap the radical(s) with nitric
      oxide (NO). NO quenched the EPR signal generated by reaction of purified ram
      seminal vesicle PGHS with arachidonic acid, suggesting that NO coupled with a
      tyrosyl radical to form inter alia nitrosocyclohexadienone. Subsequent formation
      of nitrotyrosine was detected by Western blotting of PGHS incubated with NO and
      arachidonic acid or organic hydroperoxides using an antibody against
      nitrotyrosine. Both arachidonic acid and NO were required to form nitrotyrosine,
      and tyrosine nitration was blocked by the PGHS inhibitor indomethacin. The
      presence of superoxide dismutase had no effect on nitration, indicating that
      peroxynitrite was not the nitrating agent. To identify which tyrosines were
      nitrated, PGHS was digested with trypsin, and the resulting peptides were
      separated by high pressure liquid chromatography and monitored with a diode array
      detector. A single peptide was detected that exhibited a spectrum consistent with
      the presence of nitrotyrosine. Consistent with Western blotting results, both NO
      and arachidonic acid were required to observe nitration of this peptide, and its
      formation was blocked by the PGHS inhibitor indomethacin. Peptide sequencing
      indicated that the modified residue was tyrosine 385, the source of the putative
      catalytically active tyrosyl radical.

PMID- 9535873
TI  - A new human selenium-containing protein. Purification, characterization, and cDNA
      sequence.
AB  - Selenium which occurs in proteins as the amino acid, selenocysteine, is essential
      for numerous biological processes and for human health. A prominent 75Se-labeled
      protein detected in human T-cells migrated as a 15-kDa band by SDS-polyacrylamide
      gel electrophoresis. This protein subunit was purified and subjected to tryptic
      digestion and peptide sequence analyses. Sequences of tryptic peptides derived
      from the protein corresponded to a human placental gene sequence containing an
      open reading frame of 162 residues and a readthrough in-frame TGA codon. Three
      different peptide sequences of the 15-kDa protein corresponded to a nucleotide
      sequence located downstream of this codon, suggesting that the T-cell 15-kDa
      selenoprotein contains a selenocysteine residue encoded by TGA. Post
      translational processing of the N-terminal portion of the predicted gene product
      to give the 15-kDa protein was suggested on the basis of molecular mass, amino
      acid analysis, and immunoblot assays of the purified protein. The 3'-untranslated
      region (UTR) of the gene encoding the 15-kDa protein contained a sequence that is
      very similar to the canonical selenocysteine-inserting sequence element. Computer
      analysis of transcript map data bases indicated that this gene was located on
      human chromosome 1. Its coding sequence showed no homology to known protein
      encoding genes. The 15-kDa protein gene was expressed as mRNA in a wide range of
      tissues, with increased levels in the thyroid, parathyroid, and prostate-derived
      cells as evidenced by searches of partial cDNA sequences in public data bases.
      Genes corresponding to the 15-kDa selenocysteine-containing protein were found in
      mice and rats, while the corresponding genes in Caenorhabditis elegans and Brugia
      malayi contained a cysteine codon in place of TGA. The discovery of a new human
      selenoprotein provides an additional example of the role of selenium in mammalian
      systems.

PMID- 9535874
TI  - Anti-peptide antibodies detect conformational changes of the inter-SH2 domain of
      ZAP-70 due to binding to the zeta chain and to intramolecular interactions.
AB  - T cell receptor (TCR) triggering induces association of the protein tyrosine
      kinase ZAP-70, via its two src-homology 2 (SH2) domains, to di-phosphorylated
      Immunoreceptor Tyrosine-based Activation Motifs (2pY-ITAMs) present in the
      intracellular tail of the TCR-zeta chain. The crystal structure of the SH2
      domains complexed with a 2pY-ITAM peptide suggests that the 60-amino acid-long
      inter-SH2 spacer helps the SH2 domains to interact with each other to create the
      binding site for the 2pY-ITAM. To investigate whether the inter-SH2 spacer has
      additional roles in the whole ZAP-70, we raised antibodies against two peptides
      of this region and probed ZAP-70 structure under various conditions. We show that
      the reactivity of antibodies directed at both sequences was dramatically
      augmented toward the tandem SH2 domains alone compared with that of the entire
      ZAP-70. This indicates that the conformation of the inter-SH2 spacer is not
      maintained autonomously but is controlled by sequences C-terminal to the SH2
      domains, namely, the linker region and/or the kinase domain. Moreover, antibody
      binding to the same two determinants was also inhibited when ZAP-70 or the SH2
      domains bound to the zeta chain or to a 2pY-ITAM. Together, these two
      observations suggest a model in which intramolecular contacts keep ZAP-70 in a
      closed configuration with the two SH2 domains near to each other.

PMID- 9535875
TI  - Mechanism of sodium arsenite-mediated induction of heme oxygenase-1 in hepatoma
      cells. Role of mitogen-activated protein kinases.
AB  - Heme oxygenase-1 is an inducible enzyme that catalyzes heme degradation and has
      been proposed to play a role in protecting cells against oxidative stress-related
      injury. We investigated the induction of heme oxygenase-1 by the tumor promoter
      arsenite in a chicken hepatoma cell line, LMH. We identified a heme oxygenase-1
      promoter-driven luciferase reporter construct that was highly and reproducibly
      expressed in response to sodium arsenite treatment. This construct was used to
      investigate the role of mitogen-activated protein (MAP) kinases in arsenite
      mediated heme oxygenase-1 gene expression. In LMH cells, sodium arsenite,
      cadmium, and heat shock, but not heme, induced activity of the MAP kinases
      extracellular-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38. To
      examine whether these MAP kinases were involved in mediating heme oxygenase-1
      gene expression, we utilized constitutively activated and dominant negative
      components of the ERK, JNK, and p38 MAP kinase signaling pathways. Involvement of
      an AP-1 site in arsenite induction of heme oxygenase-1 gene expression was
      studied. We conclude that the MAP kinases ERK and p38 are involved in the
      induction of heme oxygenase-1, and that at least one AP-1 element (located -1576
      base pairs upstream of the transcription start site) is involved in this
      response.

PMID- 9535876
TI  - Localization of the thrombin-binding domain on prothrombin fragment 2.
AB  - Co-crystallographic studies have shown that the interaction of human prothrombin
      fragment 2 (F2) with thrombin involves the formation of salt bridges between the
      kringle inner loop of F2 and anion-binding exosite II of thrombin. When F2 binds
      to thrombin, it has been shown to evoke conformational changes at the active site
      and at exosite I of the enzyme. Using plasma, recombinant, and synthetic F2
      peptides (F2, rF2, and sF2, respectively) we have further localized the thrombin
      binding domain on F2. F2, rF2-(1-116), rF2-(55-116), and sF2-(63-116), all of
      which contain the kringle inner loop (residues 64-93) and the acidic COOH
      terminal connecting peptide (residues 94-116), bind to thrombin-agarose. In
      contrast, analogues of the kringle inner loop, sF2-(63-90), or the COOH-terminal
      connecting peptide, sF2-(92-116), do not bind. Thus, contrary to predictions from
      the crystal structure, the COOH-terminal connecting peptide as well as the
      kringle inner loop are involved in the interaction of F2 with thrombin. F2 and
      sF2-(63-116) bind saturably to fluorescently labeled active site-blocked thrombin
      with Kd values of 4.1 and 51.3 microM, respectively. The affinity of sF2-(63-116)
      for thrombin increases about 5-fold (Kd = 10 microM) when Val at position 78 is
      substituted with Glu. F2 and sF2-(63-116) bind to exosite II on thrombin because
      both reduce the heparin-catalyzed rate of thrombin inhibition by antithrombin
      approximately 4-fold. In contrast, only F2 slows the uncatalyzed rate of thrombin
      inactivation by antithrombin. Like F2, sF2-(63-116) induces allosteric changes in
      the active site and exosite I of thrombin because it alters the rates of thrombin
      mediated hydrolysis of chromogenic substrates and displaces fluorescently labeled
      hirudin54-65 from active site-blocked thrombin, respectively. Both peptides also
      prolong the thrombin clotting time of fibrinogen in a concentration-dependent
      fashion, reflecting their effects on the active site and/or exosite I. These
      studies provide further insight into the regions of F2 that evoke functional
      changes in thrombin.

PMID- 9535877
TI  - Inhibitory properties of the regulatory domains of human protein kinase Calpha
      and mouse protein kinase Cepsilon.
AB  - Two fusion proteins in which the regulatory domains of human protein kinase
      Calpha (Ralpha; amino acids 1-270) or mouse protein kinase Cepsilon (Repsilon;
      amino acids 1-385) were linked in frame with glutathione S-transferase (GST) were
      examined for their abilities to inhibit the catalytic activities of protein
      kinase Calpha (PKCalpha) and other protein kinases in vitro. Both GST-Ralpha and
      GST-Repsilon but not GST itself potently inhibited the activities of lipid
      activated rat brain PKCalpha. In contrast, the fusion proteins had little or no
      inhibitory effect on the activities of the Ser/Thr protein kinases cAMP-dependent
      protein kinase, cGMP-dependent protein kinase, casein kinase II, myosin light
      chain kinase, and mitogen activated protein kinase or on the src Tyr kinase. GST
      Ralpha and GST-Repsilon, on a molar basis, were 100-200-fold more potent
      inhibitors of PKCalpha activity than was the pseudosubstrate peptide PKC19-36. In
      addition, a GST-Ralpha fusion protein in which the first 32 amino acids of Ralpha
      were deleted (including the pseudosubstrate sequence from amino acids 19-31) was
      an effective competitive inhibitor of PKCalpha activity. The three GST-R fusion
      proteins also inhibited protamine-activated PKCalpha and proteolytically
      activated PKCalpha (PKM), two lipid-independent forms of PKCalpha; however, the
      IC50 values for inhibition were 1 order of magnitude greater than the IC50 values
      obtained in the presence of lipid. These results suggest that part of the
      inhibitory effect of the GST-R fusion proteins on lipid-activated PKCalpha may
      have resulted from sequestration of lipid activators. Nonetheless, as evidenced
      by their abilities to inhibit the lipid-independent forms of the enzyme, the GST
      R fusion proteins also inhibited PKCalpha catalytic activity through direct
      interactions. These data indicate that the R domains of PKCalpha and PKCepsilon
      are specific inhibitors of protein kinase Calpha activity and suggest that
      regions of the R domain outside the pseudosubstrate sequence contribute to
      autoinhibition of the enzyme.

PMID- 9535878
TI  - thiBPQ encodes an ABC transporter required for transport of thiamine and thiamine
      pyrophosphate in Salmonella typhimurium.
AB  - In Salmonella typhimurium, thiamine pyrophosphate (TPP) is a required cofactor
      for several enzymes in central metabolism. Herein we identify a new thi operon,
      thiBPQ (designated sfuABC in Escherichia coli), required for the transport of
      thiamine and TPP into the cell. Insertions in the operon result in strains that
      are phenotypically and biochemically defective in thiamine and TPP transport.
      Data presented herein show that this operon is transcriptionally repressed in the
      presence of exogenous thiamine, with TPP the likely regulatory molecule. This
      work represents the first identification of thiamine transport genes in bacteria
      and demonstrates the function of a proposed ABC transporter in E. coli.

PMID- 9535879
TI  - Regulatory segments of Ca2+/calmodulin-dependent protein kinases.
AB  - Catalytic cores of skeletal and smooth muscle myosin light chain kinases and
      Ca2+/calmodulin-dependent protein kinase II are regulated intrasterically by
      different regulatory segments containing autoinhibitory and calmodulin-binding
      sequences. The functional properties of these regulatory segments were examined
      in chimeric kinases containing either the catalytic core of skeletal muscle
      myosin light chain kinase or Ca2+/calmodulin-dependent protein kinase II with
      different regulatory segments. Recognition of protein substrates by the catalytic
      core of skeletal muscle myosin light chain kinase was altered with the regulatory
      segment of protein kinase II but not with smooth muscle myosin light chain
      kinase. Similarly, the catalytic properties of the protein kinase II were altered
      with regulatory segments from either myosin light chain kinase. All chimeric
      kinases were dependent on Ca2+/calmodulin for activity. The apparent
      Ca2+/calmodulin activation constant was similarly low with all chimeras
      containing the skeletal muscle catalytic core. The activation constant was
      greater with chimeric kinases containing the catalytic core of Ca2+/calmodulin
      dependent protein kinase II with its endogenous or myosin light chain kinase
      regulatory segments. Thus, heterologous regulatory segments affect substrate
      recognition and kinase activity. Furthermore, the sensitivity to calmodulin
      activation is determined primarily by the respective catalytic cores, not the
      calmodulin-binding sequences.

PMID- 9535880
TI  - Kinetic and thermodynamic studies of purine repressor binding to corepressor and
      operator DNA.
AB  - The kinetic and thermodynamic parameters for purine repressor (PurR)-operator and
      PurR-guanine binding were determined using fluorescence spectroscopy and
      nitrocellulose filter binding. Operator binding affinity was increased by the
      presence of guanine as demonstrated previously (Choi, K. Y., Lu, F., and Zalkin,
      H. (1994) J. Biol. Chem. 269, 24066-24072; Rolfes, R. J., and Zalkin, H. (1990)
      J. Bacteriol. 172, 5637-5642), and conversely guanine binding affinity was
      increased by the presence of operator. Guanine enhanced operator affinity by
      increasing the association rate constant and decreasing the dissociation rate
      constant for binding. Operator had minimal effect on the association rate
      constant for guanine binding; however, this DNA decreased the dissociation rate
      constant for corepressor by approximately 10-fold. Despite significant sequence
      and structural similarity between PurR and LacI proteins, PurR binds to its
      corepressor ligand with a lower association rate constant than LacI binds to its
      inducer ligand. However, the rate constant for PurR-guanine binding to operator
      is approximately 3-fold higher than for LacI binding to its cognate operator
      under the same solution conditions. The distinct metabolic roles of the enzymes
      under regulation by these two repressor proteins provide a rationale for the
      observed functional differences.

PMID- 9535881
TI  - Interaction of 1,1'-bi(4-anilino)naphthalene-5,5'-disulfonic acid with alpha
      crystallin.
AB  - The hydrophobic sites in alpha-crystallin were evaluated using a fluorescent
      probe 1,1'-bi(4-anilino)naphthalenesulfonic acid (bis-ANS). Approximately one
      binding site/subunit of alpha-crystallin at 25 degrees C was estimated by
      equilibrium binding and Scatchard analysis (Kd = 1.1 microM). Based on
      fluorescence titration, the dissociation constant was 0.95 microM. The number of
      bis-ANS binding sites nearly doubled upon heat treatment of the protein at 60
      degrees C. Likewise, the exposure of alpha-crystallin to 2-3 M urea resulted in
      increased binding of bis-ANS. Above 3 M urea there was a rapid loss in the
      fluorescence indicating the loss of interaction between bis-ANS and protein. The
      alpha-crystallin refolded from 6 M urea showed tryptophan fluorescence emission
      similar to the native alpha-crystallin. However, the refolded alpha-crystallin
      showed a 60% increase in bis-ANS binding, suggesting distinct changes on the
      protein surface resulting from exposure to urea similar to the changes occurring
      due to heat treatment. The fluorescence of tryptophan in native alpha-crystallin
      was quenched by the addition of bis-ANS. The quenching was inversely related to
      the amount of bis-ANS bound to alpha-crystallin. Additionally, the binding of bis
      ANS reduced the chaperone-like activity of the protein. Photolysis of bis-ANS
      alpha-crystallin complex resulted in incorporation of the probe to both A- and B
      subunits, indicating that both subunits in native alpha-crystallin contribute to
      the surface hydrophobicity of the protein.

PMID- 9535882
TI  - Vaults are up-regulated in multidrug-resistant cancer cell lines.
AB  - Vaults are 13-MDa ribonucleoprotein particles composed largely of a 104-kDa
      protein, termed major vault protein or MVP, and a small vault RNA, vRNA. While
      MVP levels have been found to increase up to 15-fold in non-P-glycoprotein
      multidrug-resistant cell lines, the levels of vault particles have not been
      investigated. As both the function of vault particles and the mechanism of drug
      resistance in non-P-glycoprotein cells are unknown, we decided to determine
      whether vault synthesis was coupled to MDR. By cloning the human gene for vRNA
      and careful quantitation of the MVP and vRNA levels in MDR cells, we find that
      vRNA is in considerable excess to MVP. Sedimentation measurements of vault
      particles in multidrug resistance cells have indeed revealed up to a 15-fold
      increase in vault synthesis, coupled with a comparable shift of associated vRNA,
      demonstrating that vault formation is limited by expression of MVP or the minor
      vault proteins. The observation that vault synthesis is linked directly to
      multidrug resistance supports a direct role for vaults in drug resistance.

PMID- 9535883
TI  - Synthesis and properties of 8-CN-flavin nucleotide analogs and studies with
      flavoproteins.
AB  - A high potential analog of riboflavin with a cyano function at the 8-position was
      synthesized by employing novel reaction conditions, starting from 8-amino
      riboflavin. This was converted to the FAD level with FAD synthetase. The reduced
      8-CN-riboflavin, unlike normal reduced flavin, has a distinctive absorption
      spectrum with two distinctive peaks in the near ultraviolet region. The oxidation
      reduction potential of the new flavin was determined to be -50 mV, approximately
      160 mV more positive than that of normal riboflavin. The 8-CN-riboflavin and 8-CN
      FMN were found to be photoreactive and need to be protected from exposure to
      light. However such complications were not encountered with protein-bound
      flavins. The apoproteins of flavodoxin and Old Yellow Enzyme (OYE) were
      reconstituted with the 8-CN-FMN and apoDAAO was reconstituted with 8-CN-FAD.
      Spectral properties of the enzyme-bound neutral and anionic semiquinones were
      determined from these reconstituted proteins. In the case of 8-CN-FMN-OYE I, it
      was shown that the comproportionation reaction of a mixture of reduced and
      oxidized enzyme bound flavin is very rapid, compared with the same reaction with
      native protein, resulting in approximately 100% thermodynamically stable anionic
      semiquinone. In the case of 8-CN-OYE I, it was shown that the rate of reduction
      of the enzyme bound flavin by NADPH is approximately 40 times faster, and the
      rate of reoxidation of reduced enzyme bound flavin by oxygen is an order of
      magnitude slower than with the normal FMN enzyme. This is in accord with the high
      oxidation-reduction potential of the flavin, which thermodynamically stabilizes
      the reduced enzyme.

PMID- 9535884
TI  - Functional properties of the type-3 InsP3 receptor in 16HBE14o- bronchial mucosal
      cells.
AB  - The type-3 inositol 1,4,5-trisphosphate (InsP3) receptor is the major isoform
      expressed in 16HBE14o- cells from bronchial mucosa, representing 93% at the mRNA
      level as determined by ratio reverse transcription-polymerase chain reaction and
      about 81% at the protein level as determined with isoform-specific antibodies
      (Sienaert, I., Huyghe, S., Parys, J. B., Malfait, M., Kunzelmann, K., De Smedt,
      H., Verleden, G. M., and Missiaen, L., Pflugers Arch. Eur. Y. Physiol., in
      press). The present 45Ca2+ efflux experiments indicate that these InsP3 receptors
      were 3 times less sensitive to InsP3 and 11 times less sensitive to ATP than
      those in A7r5 cells, where the type-1 InsP3 receptor is the main isoform. ATP did
      not increase the cooperativity of the InsP3-induced Ca2+ release in 16HBE14o-
      cells, in contrast to its effect in A7r5 cells. The sulfhydryl reagent thimerosal
      also did not stimulate InsP3-induced Ca2+ release in 16HBE14o- cells, again in
      contrast to its effect in A7r5 cells. Adenophostin A was more potent than InsP3
      in stimulating the release in both cell types. The biphasic activation of the
      InsP3 receptor by cytosolic Ca2+ occurred in both cell types. We conclude that
      Ca2+ release mediated by the type-3 InsP3 receptor mainly differs from that
      mediated by the type-1 InsP3 receptor by its lack of stimulation by sulfhydryl
      oxidation and its lower ATP and InsP3 sensitivity. The predominant expression of
      the type-3 InsP3 receptor in the bronchial mucosa may be part of a mechanism
      coping with oxidative stress in that tissue.

PMID- 9535885
TI  - On the structural changes of native human alpha2-macroglobulin upon proteinase
      entrapment. Three-dimensional structure of the half-transformed molecule.
AB  - The reconstructions of an intermediate form of human alpha2-macroglobulin (half
      transformed alpha2M) in which two of its four bait regions and thiol ester sites
      were cleaved by chymotrypsin bound to Sepharose were obtained by three
      dimensional electron microscopy from stain and frozen-hydrated specimens. The
      structures show excellent agreement and reveal a structure with approximate
      dimensions of 195 (length) x 135 (width) and 130 A (depth) with an internal
      funnel-shaped cavity. The structure shows that a chisel-shaped body is connected
      to a broad base at the opposing end by four stands. Four approximately 45 A
      diameter large openings in the body of the structure result in a central cavity
      that is more accessible to the proteinase than those associated with the native
      or fully transformed structures. The dissimilarity in the shapes between the two
      ends of alpha2M half-transformed and the similarity between its chisel-shaped
      body and that of native alpha2M indicate that the chymotrypsin has cleaved both
      bait regions in the bottom-half of the structure. Consequently, its functional
      division lies on the minor axis. The structural organization is in accord with
      biochemical studies, which show that the half-transformed alpha2M migrates on
      native polyacrylamide gels at a rate intermediate to the native and fully
      transformed alpha2M and is capable of trapping 1 mol of proteinase. Even though
      its upper portion is similar to the native molecule, significant differences in
      their shapes are apparent and these differences may be related to its slower
      reaction with a proteinase than the native structure. These structural
      comparisons further support the view that the transformation of alpha2M involves
      an untwisting of its strands with an opening of the cavity for entrance of the
      proteinase and a retwisting of the strands around the proteinase resulting in its
      encapsulation.

PMID- 9535886
TI  - The effect of extracellular matrix proteins on porcine smooth muscle cell insulin
      like growth factor (IGF) binding protein-5 synthesis and responsiveness to IGF-I.
AB  - The aim of this study was to determine if cultured porcine vascular smooth muscle
      cells (pSMCs) that had been maintained on different extracellular matrix proteins
      had an alteration in their expression of insulin-like growth factor binding
      protein-5 (IGFBP-5) and their responsiveness to insulin-like growth factor-I (IGF
      I). When pSMCs were plated on fibronectin, they synthesized 6.0 +/- 1.2-fold more
      IGFBP-5 than did cells maintained on laminin and type IV collagen. IGF-I
      increased IGFBP-5 gene expression 3-fold in the cells plated on fibronectin. The
      addition of an RGD peptide and echistatin to pSMC cultures that had been plated
      on fibronectin inhibited IGFBP-5 mRNA expression. The addition of an antibody
      against alpha2beta1 integrin partially reversed the inhibitory effects of laminin
      and type IV collagen on IGFBP-5 expression. Cells maintained on fibronectin had a
      5.0 +/- 1.1-fold greater DNA synthesis response to IGF-I compared with those
      maintained on laminin/type IV collagen, and echistatin significantly inhibited
      the DNA synthesis response of the fibronectin-maintained cells to IGF-I. The anti
      alpha2beta1 antibody partially reversed the inhibitory effect of laminin and type
      IV collagen on IGF-I-stimulated DNA synthesis. The addition of IGFBP-5 to
      cultures plated on laminin and type IV collagen significantly increased their
      response to IGF-I. Atherosclerotic plaques from pig aorta contained abundant
      fibronectin and had increased IGFBP-5 mRNA (4.5 +/- 1.5-fold) compared with
      tissue from the normal vessel wall that had a low fibronectin content. These
      results indicate that fibronectin, laminin, and type IV collagen have major
      effects on IGFBP-5 expression and on IGF-I-stimulated pSMC responses and that
      these effects are mediated by their respective integrins.

PMID- 9535887
TI  - Efficient conditional transgene expression in hepatitis C virus cDNA transgenic
      mice mediated by the Cre/loxP system.
AB  - Conditional gene expression has greatly facilitated the examination of the
      functions of particular gene products. Using the Cre/loxP system, we developed
      efficient conditional transgene activation of hepatitis C virus (HCV) cDNA
      (nucleotides 294-3435) in transgenic mice. Efficient recombination was observed
      in transgenic mouse liver upon intravenous administration of adenovirus that
      expresses Cre DNA recombinase. After transgene activation, most hepatocytes were
      stained with anti-core polyclonal antibody, and 21-, 37-, and 64-kDa proteins
      were detected by Western blot analysis in liver lysates using anti-core, E1, and
      E2 monoclonal antibodies, respectively. Serum core protein was detected in
      transgenic mice 7 days after transgene activation with concurrent increases in
      serum alanine aminotransferase levels. Subsequently, an anti-core antibody
      response was detected 14 days after infection. Furthermore, a CD4 and CD8
      positive cell depletion assay normalized both the serum alanine aminotransferase
      increases and pathological changes in the liver. These results suggest that HCV
      proteins are not directly cytopathic and that the host immune response plays a
      pivotal role in HCV infection. Thus, this HCV cDNA transgenic mouse provides a
      powerful tool with which to investigate the immune responses and pathogenesis of
      HCV infection.

PMID- 9535888
TI  - Interactions of the borna disease virus P, N, and X proteins and their functional
      implications.
AB  - Borna disease virus (BDV) causes persistent central nervous system infection and
      behavioral disturbances in warm-blooded animals. Protein interaction studies were
      pursued to gain insight into the functions of the putative nucleoprotein (N),
      phosphoprotein (P), atypical glycoprotein (gp18), and X protein (X) of BDV.
      Coimmunoprecipitation experiments indicated that N and P, and P and X, form
      complexes in infected cells. Two-hybrid analyses confirmed interactions between P
      and P, P and X, and P and N, but not between P and gp18, N and gp18, X and gp18,
      or X and N. Analysis of P truncation mutants identified three nonoverlapping
      regions important for oligomerization (amino acids (aa) 135-172), and binding to
      X (aa 33-115) or N (aa 197-201). Coexpression of X stimulated oligomerization of
      P but decreased N-P complex formation. Immunocytochemistry of transfected
      noninfected CHO cells demonstrated that the distribution of X is dependent upon
      the presence of P-X expressed alone was found predominantly in the cytoplasm
      whereas coexpression of X and P resulted in nuclear localization.
      Immunocytochemistry of infected cells revealed nuclear colocalization of P and X.
      Interactions of P, N, and X may have implications for regulation of BDV
      transcription/replication and ribonucleoprotein assembly.

PMID- 9535889
TI  - Structural analyses and dynamics of soluble and cell wall-bound phenolics in a
      broad spectrum resistance to the powdery mildew fungus in barley.
AB  - High pressure liquid chromatography profiles of barley leaf epidermal soluble and
      cell wall-bound phenolics were analyzed in response to challenge with the fungal
      pathogen Erysiphe graminis f. sp. hordei. Only one soluble phenolic was found to
      accumulate differentially in a broad spectrum resistance reaction controlled by
      mlo resistance alleles in comparison to susceptible near isogenic Mlo lines.
      Structural analysis identified this compound as a novel phenolic conjugate, p
      coumaroyl-hydroxyagmatine (p-CHA). p-CHA but not the nonhydroxylated derivative p
      coumaroylagmatine exhibited antifungal activity both in vitro and in vivo. The
      accumulation of p-CHA in epidermal tissue correlated tightly with fungal
      penetration attempts of attacked host cells. Furthermore, upon penetration,
      epidermal cell wall-bound phenolics became resistant to saponification at sites
      of attempted fungal ingress (papilla), indicating a change in, or the addition
      of, different chemical bonding types. The switch in saponification sensitivity
      occurred at least 2 h earlier in the mlo-incompatible than in the Mlo-compatible
      interaction. Our results suggest that p-CHA and the speed of papillae compaction
      play important roles in non-race-specific powdery mildew defense.

PMID- 9535890
TI  - Insights into the molecular basis of salt tolerance from the study of glutamate
      dehydrogenase from Halobacterium salinarum.
AB  - A homology-based modeling study on the extremely halophilic glutamate
      dehydrogenase from Halobacterium salinarum has been used to provide insights into
      the molecular basis of salt tolerance. The modeling reveals two significant
      differences in the characteristics of the surface of the halophilic enzyme that
      may contribute to its stability in high salt. The first of these is that the
      surface is decorated with acidic residues, a feature previously seen in
      structures of halophilic enzymes. The second is that the surface displays a
      significant reduction in exposed hydrophobic character. The latter arises not
      from a loss of surface-exposed hydrophobic residues, as has previously been
      proposed, but from a reduction in surface-exposed lysine residues. This is the
      first report of such an observation.

PMID- 9535891
TI  - A chimeric protein C containing the prothrombin Gla domain exhibits increased
      anticoagulant activity and altered phospholipid specificity.
AB  - To determine the structural basis of phosphatidylethanolamine (PE)-dependent
      activated protein C (APC) activity, we prepared a chimeric molecule in which the
      Gla domain and hydrophobic stack of protein C were replaced with the
      corresponding region of prothrombin. APC inactivation of factor Va was enhanced
      10-20-fold by PE. Protein S enhanced inactivation 2-fold and independently of PE.
      PE and protein S had little effect on the activity of the chimera. Factor Va
      inactivation by APC was approximately 5-fold less efficient than with the chimera
      on vesicles lacking PE and slightly more efficient on vesicles containing PE. The
      cleavage patterns of factor Va by APC and the chimera were similar, and PE
      enhanced the rate of Arg506 and Arg306 cleavage by APC but not the chimera. APC
      and the chimera bound to phosphatidylserine:phosphatidylcholine vesicles with
      similar affinity (Kd approximately 500 nM), and PE increased affinity 2-3-fold.
      Factor Va and protein S synergistically increased the affinity of APC on vesicles
      without PE to 140 nM and with PE to 14 nM, but they were less effective in
      enhancing chimera binding to either vesicle. In a factor Xa one-stage plasma
      clotting assay, the chimera had approximately 5 times more anticoagulant activity
      than APC on PE-containing vesicles. Unlike APC, which showed a 10 fold dependence
      on protein S, the chimera was insensitive to protein S. To map the site of the PE
      and protein S dependence further, we prepared a chimera in which residues 1-22
      were derived from prothrombin and the remainder were derived from protein C. This
      protein exhibited PE and protein S dependence. Thus, these special properties of
      the protein C Gla domain are resident outside of the region normally hypothesized
      to be critical for membrane interaction. We conclude that the protein C Gla
      domain possesses unique properties allowing synergistic interaction with factor
      Va and protein S on PE-containing membranes.

PMID- 9535893
TI  - Characterization of a partially folded monomer of the DNA-binding domain of human
      papillomavirus E2 protein obtained at high pressure.
AB  - The pressure-induced dissociation of the dimeric DNA binding domain of the E2
      protein of human papillomavirus (E2-DBD) is a reversible process with a Kd of 5.6
      x 10(-8) M at pH 5.5. The complete exposure of the intersubunit tryptophans to
      water, together with the concentration dependence of the pressure effect, is
      indicative of dissociation. Dissociation is accompanied by a decrease in volume
      of 76 ml/mol, which corresponds to an estimated increase in solvent-exposed area
      of 2775 A2. There is a decrease in fluorescence polarization of tryptophan
      overlapping the red shift of fluorescence emission, supporting the idea that
      dissociation of E2-DBD occurs in parallel with major changes in the tertiary
      structure. The dimer binds bis(8-anilinonaphthalene-1-sulfonate), and pressure
      reduces the binding by about 30%, in contrast with the almost complete loss of
      dye binding in the urea-unfolded state. These results strongly suggest the
      persistence of substantial residual structure in the high pressure state. Further
      unfolding of the high pressure state was produced by low concentrations of urea,
      as evidenced by the complete loss of bis(8-anilinonaphthalene-1-sulfonate)
      binding with less than 1 M urea. Following pressure dissociation, a partially
      folded state is also apparent from the distribution of excited state lifetimes of
      tryptophan. The combined data show that the tryptophans of the protein in the
      pressure-dissociated state are exposed long enough to undergo solvent relaxation,
      but the persistence of structure is evident from the observed internal quenching,
      which is absent in the completely unfolded state. The average rotational
      relaxation time (derived from polarization and lifetime data) of the pressure
      induced monomer is shorter than the urea-denatured state, suggesting that the
      species obtained under pressure are more compact than that unfolded by urea.

PMID- 9535892
TI  - Folding a WD repeat propeller. Role of highly conserved aspartic acid residues in
      the G protein beta subunit and Sec13.
AB  - The beta subunit of the heterotrimeric G proteins that transduce signals across
      the plasma membrane is made up of an amino-terminal alpha-helical segment
      followed by seven repeating units called WD (Trp-Asp) repeats that occur in about
      140 different proteins. The seven WD repeats in Gbeta, the only WD repeat protein
      whose crystal structure is known, form seven antiparallel beta sheets making up
      the blades of a toroidal propeller structure (Wall, M. A., Coleman, D. E., Lee,
      E., Iniguez-Lluhi, J. A., Posner, B. A., Gilman, A. G., and Sprang, S. R. (1995)
      Cell 83, 1047-1058; Sondek, J., Bohm, A., Lambright, D. G., Hamm, H. E., and
      Sigler, P. B. (1996) Nature 379, 369-374). It is likely that all proteins with WD
      repeats form a propeller structure. Alignment of the sequence of 918 unique WD
      repeats reveals that 85% of the repeats have an aspartic acid (D) residue (not
      the D of WD) in the turn connecting beta strands b and c of each putative
      propeller blade. We mutated each of these conserved Asp residues to Gly
      individually and in pairs in Gbeta and in Sec13, a yeast WD repeat protein
      involved in vesicular traffic, and then analyzed the ability of the mutant
      proteins to fold in vitro and in COS-7 cells. In vitro, most single mutant Gbeta
      subunits fold into Gbetagamma dimers more slowly than wild type to a degree that
      varies with the blade. In contrast, all single mutants form normal amounts of
      Gbetagamma in COS-7 cells, although some dimers show subtle local distortions of
      structure. Most double mutants assemble poorly in both systems. We conclude that
      the conserved Asp residues are not equivalent and not all are essential for the
      folding of the propeller structure. Some may affect the folding pathway or the
      affinity for chaperonins. Mutations of the conserved Asp in Sec13 affect folding
      equally in vitro and in COS-7 cells. The repeats that most affected folding were
      not at the same position in Sec13 and Gbeta. Our finding, both in Gbeta and in
      Sec13, that no mutation of the conserved Asp entirely prevents folding suggests
      that there is no obligatory folding order for each repeat and that the folding
      order is probably not the same for different WD repeat proteins, or even
      necessarily constant for the same protein.

PMID- 9535894
TI  - Functional and structural heterogeneity of the DNA binding site of the
      Escherichia coli primary replicative helicase DnaB protein.
AB  - The structure-function relationship within the DNA binding site of the
      Escherichia coli replicative helicase DnaB protein was studied using nuclease
      digestion, quantitative fluorescence titration, centrifugation, and fluorescence
      energy transfer techniques. Nuclease digestion of the enzyme-single-stranded DNA
      (ssDNA) complexes reveals large structural heterogeneity within the binding site.
      The total site is built of two subsites differing in structure and affinity,
      although both occlude approximately 10 nucleotides. ssDNA affinity for the strong
      subsite is approximately 3 orders of magnitude higher than that for the weak
      subsite. Fluorescence energy transfer experiments provide direct proof that the
      DnaB hexamer binds ssDNA in a single orientation, with respect to the polarity of
      the sugar-phosphate backbone. This is the first evidence of directional binding
      to ssDNA of a hexameric helicase in solution. The strong binding subsite is close
      to the small 12-kDa domains of the DnaB hexamer and occludes the 5'-end of the
      ssDNA. The strict orientation of the helicase on ssDNA indicates that, when the
      enzyme approaches the replication fork, it faces double-stranded DNA with its
      weak subsite. The data indicate that the different binding subsites are located
      sequentially, with the weak binding subsite constituting the entry site for
      double-stranded DNA of the replication fork.

PMID- 9535895
TI  - Activity of cyclic AMP phosphodiesterases and adenylyl cyclase in peripheral
      nerve after crush and permanent transection injuries.
AB  - Recent studies demonstrate that cAMP levels are tightly controlled during
      demyelination and remyelination in Schwann cells as cAMP decreases to 8-10% of
      normal following both sciatic nerve crush or permanent transection injury and
      only begins to increase in the crushed nerve after remyelination (Poduslo, J. F.,
      Walikonis, R. S., Domec, M., Berg, C. T., and Holtz-Heppelmann, C. J. (1995) J.
      Neurochem. 65, 149-159). To investigate the mechanisms responsible for this
      change in cAMP levels, cAMP phosphodiesterase (PDE) and adenylyl cyclase
      activities were determined before and after sciatic nerve injury. Basal cAMP PDE
      activity in soluble endoneurial homogenates of normal nerve was 34.9 +/- 1.9
      pmol/mg of protein/min (chi +/- S.E.; n = 10). This activity increased about 3
      fold within 6 days following both injuries. Basal PDE activity remained elevated
      in the transected nerve, but declined to 70 pmol/mg of protein/min in the crushed
      nerve at 21 and 35 days following injury. Isozyme-specific inhibitors and
      stimulators were used to identify the PDE families in the sciatic nerve. The low
      Km cAMP-specific (PDE4) and the Ca2+/calmodulin-stimulated (PDE1) families were
      found to predominate in assays using endoneurial homogenates. The PDE4 inhibitor
      rolipram also increased cAMP levels significantly after incubation of endoneurial
      tissue with various isozyme-specific inhibitors, indicating that PDE4 plays a
      major role in determining cAMP levels. PDE4 mRNA was localized by in situ
      hybridization to cells identified as Schwann cells by colabeling of S100, a
      Schwann cell specific protein. Adenylyl cyclase activity declined following
      injury, from 3.7 pmol/mg of protein/min in normal nerve to 0.70 pmol/mg/min by 7
      days following injury. Both decreased synthesis and increased degradation
      contribute, therefore, to the reduced levels of cAMP following peripheral nerve
      injury and are likely critical to the process of Wallerian degeneration.

PMID- 9535896
TI  - The epidermal growth factor receptor modulates the interaction of E-cadherin with
      the actin cytoskeleton.
AB  - Alterations in the expression or function of molecules that affect cellular
      adhesion and proliferation are thought to be critical events for tumor
      progression. Loss of expression of the cell adhesion molecule E-cadherin and
      increased expression of the epidermal growth factor receptor are two prominent
      molecular events that are associated with tumorigenesis. The regulation of E
      cadherin-dependent cell adhesion by epidermal growth factor (EGF) was therefore
      examined in the human breast cancer cell line, MDA-MB-468. In this study, changes
      were observed in the subcellular distribution of components that mediate the
      cytoplasmic connection between E-cadherin and the actin-based cytoskeleton in
      response to activation of the EGF receptor. Serum withdrawal activated E-cadherin
      dependent cell-cell aggregation in MDA-MB-468 cells, and this treatment
      stimulated the interaction of actin, alpha-actinin, and vinculin with E-cadherin
      complexes, despite the absence of alpha-catenin in these cells. By contrast, the
      co-precipitation of actin with E-cadherin was not detected in several alpha
      catenin positive epithelial cell lines. Treatment with EGF inhibited cellular
      aggregation but did not affect either the levels of E-cadherin or catenin
      expression nor the association of catenins (beta-catenin, plakoglobin/gamma
      catenin, or p120(cas)) with E-cadherin. However, EGF treatment of the MDA-MB-468
      cell line dissociated actin, alpha-actinin, and vinculin from the E-cadherin
      catenin complex, and this coincided with a robust phosphorylation of beta
      catenin, plakoglobin/gamma-catenin, and p120(cas) on tyrosine residues.
      Furthermore, inactivation of the EGF receptor in serum-treated MDA-MB-468 cells
      with either a function-blocking antibody or EGF receptor kinase inhibitors
      mimicked the effects of serum starvation by stimulating both cellular aggregation
      and assembly of E-cadherin complexes with vinculin and actin. These results
      demonstrate that the EGF receptor directly regulates cell-cell adhesion through
      modulation of the interaction of E-cadherin with the actin cytoskeleton and thus
      substantiates the coordinate role of both of these molecules in tumor progression
      and metastasis.

PMID- 9535897
TI  - Alteration of the midpoint potential and catalytic activity of the rieske iron
      sulfur protein by changes of amino acids forming hydrogen bonds to the iron
      sulfur cluster.
AB  - The crystal structure of the bovine Rieske iron-sulfur protein indicates a sulfur
      atom (S-1) of the iron-sulfur cluster and the sulfur atom (Sgamma) of a cysteine
      residue that coordinates one of the iron atoms form hydrogen bonds with the
      hydroxyl groups of Ser-163 and Tyr-165, respectively. We have altered the
      equivalent Ser-183 and Tyr-185 in the Saccharomyces cerevisiae Rieske iron-sulfur
      protein by site-directed mutagenesis of the iron-sulfur protein gene to examine
      how these hydrogen bonds affect the midpoint potential of the iron-sulfur cluster
      and how changes in the midpoint potential affect the activity of the enzyme.
      Eliminating the hydrogen bond from the hydroxyl group of Ser-183 to S-1 of the
      cluster lowers the midpoint potential of the cluster by 130 mV, and eliminating
      the hydrogen bond from the hydroxyl group of Tyr-185 to Sgamma of Cys-159 lowers
      the midpoint potential by 65 mV. Eliminating both hydrogen bonds has an
      approximately additive effect, lowering the midpoint potential by 180 mV. Thus,
      these hydrogen bonds contribute significantly to the positive midpoint potential
      of the cluster but are not essential for its assembly. The activity of the bc1
      complex decreases with the decrease in midpoint potential, confirming that
      oxidation of ubiquinol by the iron-sulfur protein is the rate-limiting partial
      reaction in the bc1 complex, and that the rate of this reaction is extensively
      influenced by the midpoint potential of the iron-sulfur cluster.

PMID- 9535898
TI  - The cytoplasmic tail of the vesicular acetylcholine transporter contains a
      synaptic vesicle targeting signal.
AB  - The human homologue of the vesicular acetylcholine transporter (hVAChT) and the
      neuronal isoform of the vesicular monoamine transporter (hVMAT2) are
      differentially targeted to two populations of regulated secretory organelles when
      expressed in PC12 cells. Western blot analysis of subcellular fractions from
      sucrose equilibrium density gradients and glycerol velocity gradients of
      homogenates from stably transfected cells revealed hVAChT immunoreactivity in
      fractions that contain synaptophysin, a marker of synaptic vesicles, while hVMAT2
      immunoreactivity was confined to heavy fractions containing chromogranin B, a
      marker of large dense core vesicles. In cells treated with nerve growth factor,
      hVAChT immunoreactivity alone co-localized with synaptophysin and was abundantly
      expressed on synaptic vesicle clusters. Chimeras between hVMAT2 and hVAChT were
      utilized to identify the domain of hVAChT required for its expression on synaptic
      vesicles and which would shift the expression of hVMAT2 from large dense core
      vesicles to synaptic vesicles. Biochemical, immunocytochemical, and electron
      microscopic analyses revealed that a chimera in which the cytoplasmic tail of
      hVMAT2 was replaced with hVAChT sequences was now preferentially targeted to
      synaptic vesicles. In addition, hVAChT expression on synaptic vesicles was nearly
      abolished when the hVMAT2 cytoplasmic tail was present. Thus, structural
      information resides within the terminal cytoplasmic domain of VAChT, which
      specifically targets it to synaptic vesicles.

PMID- 9535899
TI  - The centromeric/nucleolar chromatin protein ZFP-37 may function to specify
      neuronal nuclear domains.
AB  - Murine ZFP-37 is a member of the large family of C2H2 type zinc finger proteins.
      It is characterized by a truncated NH2-terminal Kruppel-associated box and is
      thought to play a role in transcriptional regulation. During development Zfp-37
      mRNA is most abundant in the developing central nervous system, and in the adult
      mouse expression is restricted largely to testis and brain. Here we show that at
      the protein level ZFP-37 is detected readily in neurons of the adult central
      nervous system but hardly in testis. In brain ZFP-37 is associated with nucleoli
      and appears to contact heterochromatin. Mouse and human ZFP-37 have a basic
      histone H1-like linker domain, located between KRAB and zinc finger regions,
      which binds double-stranded DNA. Thus we suggest that ZFP-37 is a structural
      protein of the neuronal nucleus which plays a role in the maintenance of
      specialized chromatin domains.

PMID- 9535900
TI  - Differential effects of Ca2+ channel beta1a and beta2a subunits on complex
      formation with alpha1S and on current expression in tsA201 cells.
AB  - To study the interactions of the alpha1S subunit of the skeletal muscle L-type
      Ca2+ channel with the skeletal beta1a and the cardiac beta2a, these subunits were
      expressed alone or in combination in tsA201 cells. Immunofluorescence- and green
      fluorescent protein-labeling showed that, when expressed alone, beta1a was
      diffusely distributed throughout the cytoplasm, beta2a was localized in the
      plasma membrane, and alpha1S was concentrated in a tubular/reticular membrane
      system, presumably the endoplasmic reticulum (ER). Upon coexpression with
      alpha1S, beta1a became colocalized with alpha1S in the ER. Upon coexpression with
      beta2a, alpha1S redistributed to the plasma membrane, where it aggregated in
      large clusters. Coexpression of alpha1S with beta1a but not with beta2a increased
      the frequency at which cells expressed L-type currents. A point mutation (alpha1S
      Y366S) or deletion (alpha1S-Delta351-380) in the beta interaction domain of
      alpha1S blocked both translocation of beta1a to the ER and beta2a-induced
      translocation of the alpha1S mutants to the plasma membrane. However, the point
      mutation did not interfere with beta1a-induced current stimulation. Thus, beta1a
      and beta2a are differentially distributed in tsA201 cells and upon coexpression
      with alpha1S, form alpha1S. beta complexes in different cellular compartments.
      Complex formation but not current stimulation requires the intact beta
      interaction domain in the I-II cytoplasmic loop of alpha1S.

PMID- 9535901
TI  - Stopped flow fluorescence energy transfer measurement of the rate constants
      describing the reversible formation and the irreversible rearrangement of the
      elastase-alpha1-proteinase inhibitor complex.
AB  - Serpins are thought to inhibit proteinases by first forming a Michaelis-type
      complex that later converts into a stable inhibitory species. However, there is
      only circumstantial evidence for such a two-step reaction pathway. Here we
      directly observe the sequential appearance of two complexes by measuring the time
      dependent change in fluorescence resonance energy transfer between fluorescein
      elastase and rhodamine-alpha1-protease inhibitor. A moderately tight initial
      Michaelis-type complex EI1 (Ki = 0.38-0.52 microM) forms and dissociates rapidly
      (k1 = 1.5 x 10(6) M-1 s-1, k-1 = 0.58 s-1). EI1 then slowly converts into EI2 (k2
      = 0.13 s-1), the fluorescence intensity of which is stable for at least 50 s. The
      two species differ by their donor-acceptor energy transfer efficiency (0. 41 and
      0.26, respectively). EI2 might be the final product of the elastase + inhibitor
      association because its transfer efficiency is the same as that of a complex
      incubated for 30 min. The time-dependent change in fluorescence resonance energy
      transfer between fluorescein-elastase and rhodamine-eglin c, a canonical
      inhibitor, again allows the fast formation of a complex to be observed. However,
      this complex does not undergo any fluorescently detectable transformation.

PMID- 9535902
TI  - GATA factor-dependent regulation of cardiac m2 muscarinic acetylcholine gene
      transcription.
AB  - The m2 subtype is the predominant muscarinic acetylcholine receptor subtype
      expressed in heart and regulates the rate and force of cardiac contraction. We
      have previously reported the isolation of the promoter region for the chick m2
      receptor gene and defined a region of the chick m2 promoter sufficient for high
      level expression in cardiac primary cultures. In this manuscript we demonstrate
      transactivation of cm2 promoter by the GATA family of transcription factors. In
      addition, we define the GATA-responsive element in the chick m2 promoter and
      demonstrate that this element is required for expression in cardiac primary
      cultures. Finally, we demonstrate specific binding of both a chick heart nuclear
      protein and of cloned chick GATA-4, -5, and -6 to the GATA-responsive element.

PMID- 9535903
TI  - GM3-enriched microdomain involved in cell adhesion and signal transduction
      through carbohydrate-carbohydrate interaction in mouse melanoma B16 cells.
AB  - Mouse melanoma B16 cells are characterized by the predominant presence of
      ganglioside GM3 and adhere to lactosylceramide- or Gg3-coated plates through
      interaction of GM3 with lactosylceramide or Gg3, whereby not only adhesion but
      also spreading and enhancement of cell motility occur (Kojima, N., Hakomori, S.
      (1991) J. Biol. Chem. 266, 17552-17558). We now report that the adhesion process
      is based essentially on a glycosphingolipid-enriched microdomain (GEM) at the B16
      cell surface, since >90% of GM3 present in the original cells is found in GEM,
      and GEM is also enriched in several signal transducer molecules, e.g. c-Src, Ras,
      Rho, and focal adhesion kinase (FAK). GEM was isolated as a low density
      membranous fraction by homogenization of B16 cells in lysis buffer under two
      different conditions (i.e. buffer containing 1% Triton X-100, or hypertonic
      sodium carbonate without detergent), followed by sucrose density gradient
      centrifugation. A close association of GM3 with c-Src, Rho, and FAK was indicated
      by co-immunoprecipitation of GM3 present in GEM by anti-GM3 monoclonal antibody
      DH2, followed by Western blotting with antibodies directed to these transducer
      molecules. The following data indicate that GEM is a structural and functional
      unit for initiation of GM3-dependent cell adhesion coupled with signal
      transduction. 1) Tyrosine phosphorylation in FAK was greatly enhanced in B16
      cells adhered to Gg3-coated plates but was minimal in cells adhered to GM3
      coated, GlcCer-coated, or noncoated plates. 2) GTP loading on Ras and Rho
      increased significantly when cells were adhered to Gg3-coated plates, compared
      with GM3-coated, GlcCer-coated, or noncoated plates. Since Ras and Rho are
      closely associated with GM3 in GEM, cell adhesion/stimulation through GM3 in GEM
      may induce activation of Ras and Rho through enhanced GTP binding.

PMID- 9535904
TI  - Definition of regulatory sequence elements in the promoter region and the first
      intron of the myotonic dystrophy protein kinase gene.
AB  - Myotonic dystrophy is the most common inherited adult neuromuscular disorder with
      a global frequency of 1/8000. The genetic defect is an expanding CTG
      trinucleotide repeat in the 3'-untranslated region of the myotonic dystrophy
      protein kinase gene. We present the in vitro characterization of cis regulatory
      elements controlling transcription of the myotonic dystrophy protein kinase gene
      in myoblasts and fibroblasts. The region 5' to the initiating ATG contains no
      consensus TATA or CCAAT box. We have mapped two transcriptional start sites by
      primer extension. Deletion constructs from this region fused to the bacterial
      chloramphenicol acetyltransferase reporter gene revealed only subtle muscle
      specific cis elements. The strongest promoter activity mapped to a 189-base pair
      fragment. This sequence contains a conserved GC box to which the transcription
      factor Sp1 binds. Reporter gene constructs containing a 2-kilobase pair first
      intron fragment of the myotonic dystrophy protein kinase gene enhances reporter
      activity up to 6-fold in the human rhabdomyosarcoma myoblast cell line TE32 but
      not in NIH 3T3 fibroblasts. Co-transfection of a MyoD expression vector with
      reporter constructs containing the first intron into 10 T1/2 fibroblasts resulted
      in a 10-20-fold enhancement of expression. Deletion analysis of four E-box
      elements within the first intron reveal that these elements contribute to
      enhancer activity similarly in TE32 myoblasts and 10 T1/2 fibroblasts. These data
      suggest that E-boxes within the myotonic dystrophy protein kinase first intron
      mediate interactions with upstream promoter elements to up-regulate transcription
      of this gene in myoblasts.

PMID- 9535905
TI  - Identification of a domain on the beta-subunit of the rod cGMP-gated cation
      channel that mediates inhibition by calcium-calmodulin.
AB  - The cGMP-gated cation channel mediating phototransduction in retinal rods has
      recently been shown to be inhibited by calcium-calmodulin, through direct binding
      of the latter to the beta-subunit of the heterotetrameric channel complex. Here,
      we report the characterization of this inhibition and the identification of a
      domain crucial for this modulation. Heterologous expression of the alpha- and
      beta-subunits of the human rod channel in HEK 293 cells produced a cGMP-gated
      current that was highly sensitive to calcium-calmodulin, with half-maximal
      inhibition at approximately 4 nM. In biochemical and electrophysiological
      experiments on deletion mutants of the beta-subunit, we have identified a region
      on its cytoplasmic N terminus that binds calmodulin and is necessary for the
      calmodulin-mediated inhibition of the channel. However, in gel shift assays and
      fluorescence emission experiments, peptides derived from this region indicated a
      low calmodulin affinity, with dissociation constants of approximately 3-10
      microM. On the C terminus, a region was also found to bind calmodulin, but it was
      likewise of low affinity, and its deletion did not abolish the calmodulin
      mediated inhibition. We suggest that although the identified region on the N
      terminus of the beta-subunit is crucial for the calmodulin effect, other regions
      are likely to be involved as well. In this respect, the rod channel appears to
      differ from the olfactory cyclic nucleotide-gated channel, which is also
      modulated by calcium-calmodulin.

PMID- 9535906
TI  - Caspase cleavage of gene products associated with triplet expansion disorders
      generates truncated fragments containing the polyglutamine tract.
AB  - The neurodegenerative diseases Huntington disease, dentatorubropallidoluysian
      atrophy, spinocerebellar atrophy type 3, and spinal bulbar muscular atrophy are
      caused by expansion of a polyglutamine tract within their respective gene
      products. There is increasing evidence that generation of truncated proteins
      containing an expanded polyglutamine tract may be a key step in the pathogenesis
      of these disorders. We now report that, similar to huntingtin, atrophin-1, ataxin
      3, and the androgen receptor are cleaved in apoptotic extracts. Furthermore, each
      of these proteins is cleaved by one or more purified caspases, cysteine proteases
      involved in apoptotic death. The CAG length does not modulate susceptibility to
      cleavage of any of the full-length proteins. Our results suggest that by
      generation of truncated polyglutamine-containing proteins, caspase cleavage may
      represent a common step in the pathogenesis of each of these neurodegenerative
      diseases.

PMID- 9535907
TI  - Transcriptional regulation of the human nonmuscle myosin II heavy chain-A gene.
      Identification of three clustered cis-elements in intron-1 which modulate
      transcription in a cell type- and differentiation state-dependent manner.
AB  - In an attempt to identify cis-acting elements for transcriptional regulation of
      the human nonmuscle myosin II heavy chain (MHC)-A gene, the region extending 20
      kilobases (kb) upstream and 40 kb downstream from the transcription start sites,
      which includes the entire 37-kb intron 1, was examined. Using transient
      transfection analysis of luciferase reporter constructs, a 100-base pair (bp)
      region (N2d) in intron 1, located 23 kb downstream from the transcriptional start
      sites, has been found to activate transcription in a cell type- and
      differentiation state-dependent manner. Maximum activity (approximately 20-fold)
      is seen in NIH 3T3 fibroblasts and intermediate activity (7-fold) in
      proliferating and undifferentiated C2C12 myoblasts. In contrast, this region is
      almost inactive in terminally differentiated C2C12 myotubes, in which endogenous
      nonmuscle MHC-A expression is down-regulated. Gel mobility shift assays and
      methylation interference analyses were performed using NIH 3T3 nuclear extracts
      to determine the protein-binding elements for transcription factors. Three
      binding elements have been identified within the N2d region. Antibody-supershift
      experiments, as well as competition experiments using consensus binding sequences
      for specific transcription factors, revealed that the most 5'-element, C
      (GGGAGGGGCC) is recognized specifically and exclusively by Sp1 and Sp3
      transcriptional factors. Element C is immediately followed by a novel element, A
      (GTGACCC). A third element, F (GTGTCAGGTG), which contains an E-box, is located
      50 bp 3' to element A. Element F can be recognized partially by upstream
      stimulatory factors, USF1 and/or USF2. Transfection studies with luciferase
      reporter constructs which include mutations in all three elements in various
      combinations demonstrate that the A and C binding factors cooperatively activate
      transcriptional activity in NIH 3T3 cells. The F binding factor shows an additive
      effect on transcription.

PMID- 9535908
TI  - The mammalian numb phosphotyrosine-binding domain. Characterization of binding
      specificity and identification of a novel PDZ domain-containing numb binding
      protein, LNX.
AB  - Numb is a phosphotyrosine-binding (PTB) domain-containing protein implicated in
      the control of cell fate decisions during development. A modified two-hybrid
      screen in yeast was used to identify Numb PTB domain-interacting proteins
      important for Numb function. Here we report the identification of a novel
      protein, LNX, which interacts specifically with the Numb PTB domain. Two
      differentially expressed LNX messages encode overlapping proteins with predicted
      molecular masses of 80 kDa (LNX) and 70 kDa (LNX-b). LNX and LNX-b contain unique
      amino-terminal sequences and share four PDZ domains. The unique amino-terminal
      region of LNX includes a RING finger domain. The Numb PTB domain binding region
      of LNX was mapped to the sequence motif LDNPAY, found in both protein isoforms.
      Mutational analysis of LNX and peptide competition experiments showed that
      phosphorylation of the tyrosine residue within this motif was not required for
      binding to the Numb PTB domain. Finally, we also provide evidence that tyrosine
      phosphorylation of the LDNPAY sequence motif in LNX could generate a binding site
      for the phosphorylation-dependent binding of other PTB domain-containing proteins
      such as SHC. We speculate that LNX may be important for clustering PTB-containing
      proteins with functionally related transmembrane proteins in specific membrane
      compartments.

PMID- 9535909
TI  - Regulation of connexin-43 gap junctional intercellular communication by mitogen
      activated protein kinase.
AB  - Activation of the Ras/Raf/mitogen-activated protein kinase kinase/mitogen
      activated protein (MAP) kinase signaling cascade is initiated by activation of
      growth factor receptors and regulates many cellular events, including cell cycle
      control. Our previous studies suggested that the connexin-43 gap junction protein
      may be a target of activated MAP kinase and that MAP kinase may regulate connexin
      43 function. We identified the sites of MAP kinase phosphorylation in in vitro
      studies as the consensus MAP kinase recognition sites in the cytoplasmic carboxyl
      tail of connexin-43, Ser255, Ser279, and Ser282. In this study, we demonstrate
      that activation of MAP kinase by ligand-induced activation of the epidermal
      growth factor (EGF) or lysophosphatidic acid receptors or by pervanadate-induced
      inhibition of tyrosine phosphatases results in increased phosphorylation on
      connexin-43. EGF and lysophosphatidic acid-induced phosphorylation on connexin-43
      and the down-regulation of gap junctional communication in EGF-treated cells were
      blocked by a specific mitogen-activated protein kinase kinase inhibitor (PD98059)
      that prevented activation of MAP kinase. These studies confirm that connexin-43
      is a MAP kinase substrate in vivo and that phosphorylation on Ser255, Ser279,
      and/or Ser282 initiates the down-regulation of gap junctional communication.
      Studies with connexin-43 mutants suggest that MAP kinase phosphorylation at one
      or more of the tandem Ser279/Ser282 sites is sufficient to disrupt gap junctional
      intercellular communication.

PMID- 9535910
TI  - MutS and MutL activate DNA helicase II in a mismatch-dependent manner.
AB  - MutS, MutL, and DNA helicase II are required for the mismatch-provoked excision
      step that occurs during Escherichia coli methyl-directed mismatch repair. In this
      study MutL is shown to enhance the unwinding activity of DNA helicase II more
      than 10-fold on a conventional helicase substrate in which a 35-residue
      oligonucleotide is annealed to a M13 circular single-stranded phage DNA under
      conditions where the two proteins are present at approximately molar
      stoichiometry with respect to the substrate. MutS- and MutL-dependent activation
      of DNA helicase II has also been demonstrated with a model substrate in which a
      138-residue oligonucleotide was hybridized to a 138-nucleotide gap in an
      otherwise duplex 7,100-base pair circular DNA. Displacement of the
      oligonucleotide requires MutS, MutL, DNA helicase II, and ATP and is dependent on
      the presence of a mismatch within the hybrid region. Although DNA helicase II and
      Rep helicase share substantial sequence homology and features of mechanism, Rep
      helicase is inactive in this reaction.

PMID- 9535911
TI  - Mismatch-, MutS-, MutL-, and helicase II-dependent unwinding from the single
      strand break of an incised heteroduplex.
AB  - Escherichia coli MutS, MutL, and DNA helicase II are sufficient to initiate
      mismatch-dependent unwinding of an incised heteroduplex (Yamaguchi, M., Dao, V.,
      and Modrich, P. (1998) J. Biol. Chem., 273, 9197-9201). We have studied unwinding
      of 6.4-kilobase circular G-T heteroduplexes that contain a single-strand
      incision, 808 base pairs 5' to the mismatch or 1023 base pairs 3' to the mispair
      as viewed along the shorter path between the two DNA sites. Unwinding of both
      substrates in the presence of MutS, MutL, DNA helicase II, and single-stranded
      DNA binding protein was mismatch-dependent and initiated at the single-strand
      break. Although unwinding occurred in both directions from the strand break, it
      was biased toward the shorter path linking the strand break and the mispair. MutS
      and MutL are thus sufficient to coordinate mismatch recognition to the
      orientation-dependent activation of helicase II unwinding at a single-strand
      break located a kilobase from the mispair.

PMID- 9535912
TI  - Molecular characterization and expression of heparan-sulfate 6-sulfotransferase.
      Complete cDNA cloning in human and partial cloning in Chinese hamster ovary
      cells.
AB  - Heparan-sulfate 6-sulfotransferase (HS6ST) catalyzes the transfer of sulfate from
      3'-phosphoadenosine 5'-phosphosulfate to position 6 of the N-sulfoglucosamine
      residue of heparan sulfate. The enzyme was purified to apparent homogeneity from
      the serum-free culture medium of Chinese hamster ovary (CHO) cells (Habuchi, H.,
      Habuchi, O., and Kimata, K. (1995) J. Biol Chem. 270, 4172-4179). From the amino
      acid sequence data of the purified enzyme, degenerate oligonucleotides were
      designed and used as primers for the reverse transcriptase-polymerase chain
      reaction using poly(A)+ RNA from CHO cells as a template. The amplified cDNA
      fragment was then used as a probe to screen a cDNA library of CHO cells. The cDNA
      clone thus obtained encoded a partial peptide sequence composed of 236 amino acid
      residues that included the sequences of six peptides obtained after
      endoproteinase digestion of the purified enzyme. This cDNA clone was applied to
      the screening of a human fetal brain cDNA library by cross-hybridization. The
      isolated cDNA clones contained a whole open reading frame that predicts a type II
      transmembrane protein composed of 401 amino acid residues. No significant amino
      acid sequence identity to any other proteins, including heparan-sulfate 2
      sulfotransferases, was observed. When the cDNA for the entire coding sequence of
      the protein was inserted into a eukaryotic expression vector and transfected into
      COS-7 cells, the HS6ST activity increased 7-fold over the control. The FLAG
      fusion protein purified by anti-FLAG affinity chromatography showed the HS6ST
      activity alone. Northern blot analysis revealed the occurrence of a single
      transcript of 3.9 kilobases in both human fetal brain and CHO cells. The results,
      together with the ones from our recent cDNA analysis of heparan-sulfate 2
      sulfotransferase (Kobayashi, M., Habuchi, H., Yoneda, M., Habuchi, O., and
      Kimata, K. (1997) J. Biol. Chem. 272, 13980-13985), suggest that at least two
      different gene products are responsible for 6- and 2-O-sulfations of heparan
      sulfate.

PMID- 9535913
TI  - Aberrant regulation of transforming growth factor-alpha during the establishment
      of growth arrest and quiescence of growth factor independent cells.
AB  - Autocrine transforming growth factor alpha (TGFalpha) is an important positive
      growth effector in malignant cells and plays a significant role in generating the
      growth factor-independent phenotype associated with malignant progression.
      However, the molecular mechanisms by which TGFalpha confers a growth advantage in
      progression is poorly understood. The highly tumorigenic cell line HCT116 up
      regulates TGFalpha mRNA expression during growth arrest, whereas the poorly
      tumorigenic growth factor-dependent FET cell line down-regulates TGFalpha mRNA
      expression as it becomes quiescent. We have identified a 25-bp sequence at -201
      to -225 within the TGFalpha promoter which mediates the differential regulation
      of TGFalpha expression during quiescence establishment in these two cell lines.
      This same sequence confers TGFalpha promoter responsiveness to exogenous growth
      factor or autocrine TGFalpha. The abberant upregulation of TGFalpha mRNA in
      quiescent HCT116 cells may allow them to return to the dividing state under more
      stringent conditions (nutrient replenishment alone) then quiescent FET cells
      (requires nutrients and growth factors). Antisense TGFalpha approaches showed
      that the dysregulated TGFalpha expression in quiescent HCT116 cells is a function
      of the strong TGFalpha autocrine loop (not inhibited by blocking antibodies) in
      these cells.

PMID- 9535914
TI  - Cloning and characterization of Vitis vinifera UDP-glucose:flavonoid 3-O
      glucosyltransferase, a homologue of the enzyme encoded by the maize Bronze-1
      locus that may primarily serve to glucosylate anthocyanidins in vivo.
AB  - We report here the cloning and optimized expression at 16 degrees C and the
      characterization of a Vitis vinifera UDP-glucose:flavonoid 3-O
      glucosyltransferase, an enzyme responsible for a late step in grapevine
      anthocyanin biosynthesis. The properties of this and other UDP-glucose:flavonoid
      3-O-glucosyltransferases, homologues of the product encoded by the maize Bronze-1
      locus, are a matter of conjecture. The availability of a purified recombinant
      enzyme allowed for the unambiguous determination of the characteristics of a
      flavonoid 3-O-glucosyltransferase. Kinetic analyses showed that kcat for
      glucosylation of cyanidin, an anthocyanidin substrate, is 48 times higher than
      for glucosylation of the flavonol quercetin, whereas Km values are similar for
      both substrates. Activity toward other classes of substrates is absent. Cu2+ ions
      strongly inhibit the action of this and other glucosyltransferases; however, we
      suggest that this phenomenon in large part is due to Cu2+-mediated substrate
      degradation rather than inhibition of the enzyme. Additional lines of
      complementary biochemical data also indicated that in the case of V. vinifera,
      the principal, if not only, role of UDP-glucose:flavonoid 3-O
      glucosyltransferases is to glucosylate anthocyanidins in red fruit during
      ripening. Other glucosyltransferases with a much higher relative activity toward
      quercetin are suggested to glucosylate flavonols in a distinct spatial and
      temporal pattern. It should be considered whether gene products homologous to
      Bronze-1 in some cases more accurately should be referred to as UDP
      glucose:anthocyanidin 3-O-glucosyltransferases.

PMID- 9535915
TI  - Roles of the complex formation of SHPS-1 with SHP-2 in insulin-stimulated mitogen
      activated protein kinase activation.
AB  - SHPS-1 is a receptor-like protein that undergoes tyrosine phosphorylation and
      binds SHP-2, an SH2 domain-containing protein tyrosine phosphatase, in response
      to insulin and other mitogens. The overexpression of wild-type SHPS-1, but not of
      a mutant SHPS-1 in which all four tyrosine residues in its cytoplasmic region
      were mutated to phenylalanine, markedly enhanced insulin-induced activation of
      mitogen-activated protein kinase in Chinese hamster ovary cells that overexpress
      the human insulin receptor. Mutation of each tyrosine residue individually
      revealed that the major sites of tyrosine phosphorylation of SHPS-1 in response
      to insulin are Tyr449 and Tyr473. In addition, mutation of either Tyr449 or
      Tyr473 abolished the insulin-induced tyrosine phosphorylation of SHPS-1 and its
      association with SHP-2. Surface plasmon resonance analysis showed that
      glutathione S-transferase fusion proteins containing the NH2-terminal or COOH
      terminal SH2 domains of SHP-2 bound preferentially to phosphotyrosyl peptides
      corresponding to the sequences surrounding Tyr449 or Tyr473, respectively, of
      SHPS-1. Furthermore, phosphotyrosyl peptides containing Tyr449 or Tyr473 were
      effective substrates for the phosphatase activity of recombinant SHP-2 in vitro.
      Together, these results suggest that insulin may induce phosphorylation of SHPS-1
      at Tyr449 and Tyr473, to which SHP-2 then binds through its NH2-terminal and COOH
      terminal SH2 domains, respectively. SHPS-1 may play a crucial role both in the
      recruitment of SHP-2 from the cytosol to a site near the plasma membrane and in
      increasing its catalytic activity, thereby positively regulating the RAS-mitogen
      activated protein kinase signaling cascade in response to insulin.

PMID- 9535916
TI  - Nucleotide binding to the C-terminal nucleotide binding domain of ArsA. Studies
      with an ATP analogue, 5'-p-fluorosulfonylbenzoyladenosine.
AB  - ArsA protein, the catalytic component of the plasmid-encoded anion-translocating
      ATPase in Escherichia coli, contains two consensus nucleotide binding domains, A1
      and A2, that are connected by a flexible linker. ATP has previously been shown to
      cross-link to the A1 domain upon activation with UV light but not to the A2
      domain. The ATP analogue, 5'-p-fluorosulfonylbenzoyladenosine (FSBA) was used to
      probe the nucleotide binding domains of ArsA. The covalently labeled protein was
      subjected to partial trypsin proteolysis, followed by Western blot analysis of
      the fragments with the anti-FSBA serum. The N-terminal amino acid sequence of the
      labeled fragment showed that FSBA binds preferentially to the C-terminal domain
      A2 both in the absence and the presence of antimonite. Occupancy of the two
      nucleotide binding sites was determined by protection from trypsin proteolysis.
      Trypsin cleaved the ArsA protein at Arg290 in the linker to generate a 32-kDa N
      terminal and a 27-kDa C-terminal fragment. The 32-kDa fragment is compact and
      largely inaccessible to trypsin; however, the 27-kDa was cleaved further.
      Incubation with FSBA, which binds to the C-terminal domain, resulted in
      significant protection of the 27-kDa fragment. This fragment was not protected
      upon incubation with ATP alone, indicating that A2 might be unoccupied. However,
      upon incubation with ATP and antimonite, almost complete protection from trypsin
      was seen. ATP and FSBA together mimicked the effect of ATP and antimonite,
      implying that this fully protected conformation might be the result of both sites
      occupied with the nucleotide. It is proposed that the A1 site in ArsA is a high
      affinity ATP site, whereas the allosteric ligand antimonite is required to allow
      ATP binding to A2, resulting in catalytic cooperativity. Thus antimonite binding
      may act as a switch in regulating ATP binding to A2 and hence the ATPase activity
      of ArsA.

PMID- 9535917
TI  - A homologue of Saccharomyces cerevisiae Dpm1p is not sufficient for synthesis of
      dolichol-phosphate-mannose in mammalian cells.
AB  - Dolichol-phosphate-mannose (Dol-P-Man) serves as a donor of mannosyl residues in
      major eukaryotic glycoconjugates. It donates four mannosyl residues in the N
      linked oligosaccharide precursor and all three mannosyl residues in the core of
      the glycosylphosphatidylinositol anchor. In yeasts it also donates one mannose to
      the O-linked oligosaccharide. The yeast DPM1 gene encodes a Dol-P-Man synthase
      that is a transmembrane protein expressed in the endoplasmic reticulum. We cloned
      human and mouse homologues of DPM1, termed hDPM1 and mDPM1, respectively, both of
      which encode proteins of 260 amino acids, having 30% amino acid identity with
      yeast Dpm1 protein but lacking a hydrophobic transmembrane domain, which exists
      in the yeast synthase. Human and mouse DPM1 cDNA restored Dol-P-Man synthesis in
      mouse Thy-1-deficient mutant class E cells. Mouse class E mutant cells had an
      inactivating mutation in the mDPM1 gene, indicating that mDPM1 is the gene for
      class E mutant. In contrast, hDPM1 and mDPM1 cDNA did not complement another Dol
      P-Man synthesis mutant, hamster Lec15 cells, whereas yeast DPM1 restored both
      mutants. Therefore, in contrast to yeast, mammalian cells require hDPM1/mDPM1
      protein and a product of another gene that is defective in Lec15 mutant cells for
      synthesis of Dol-P-Man.

PMID- 9535918
TI  - Heteromerization of the gammac chain with the interleukin-9 receptor alpha
      subunit leads to STAT activation and prevention of apoptosis.
AB  - Interleukin-9 (IL-9) is a cytokine with pleiotropic effects on mast cell and T
      cell lines. It exerts its effects through the IL-9R complex consisting of IL
      9Ralpha and the common gammac subunit. Here we report functional evidence for
      receptor heteromerization for efficient signal transduction, and we define
      minimal requirements in the two receptor subunits for IL-9R function. Tyrosine
      336 of the IL-9Ralpha and the membrane-proximal segment of gammac are both
      crucial for signaling. The activated IL-9R complex employs the Janus kinases JAK1
      and JAK3 for subsequent activation of the signal transducer and activator
      transcription (STAT) factors STAT-1, STAT-3, and STAT-5. This process is
      independent of Tyk2. We demonstrate further that the activated STAT complexes
      consist of STAT-1 and STAT-5 homodimers and STAT-1-STAT-3 heterodimers. Finally,
      we show that IL-9R signaling in a T cell line does not result in detectable
      mitogen-activated protein kinase activation and leads to unsustained
      proliferation. Nonetheless, these T cells are efficiently protected from
      dexamethasone-induced apoptosis. These results further define the molecular
      architecture of the IL-9R and its specific connections to various biologic
      responses.

PMID- 9535919
TI  - The switch in the helical handedness of the histone (H3-H4)2 tetramer within a
      nucleoprotein particle requires a reorientation of the H3-H3 interface.
AB  - It has recently been proposed that the histone (H3-H4)2 tetramer undergoes
      structural changes, which allow the particle to accommodate both negatively and
      positively constrained DNA. To investigate this process, we modified histone H3
      at the H3-H3 interface, within the histone (H2A-H2B-H3-H4)2 octamer or the
      histone (H3-H4)2 tetramer, by forming adducts on the single cysteine of duck
      histone H3. We used three sulfhydryl reagents, iodoacetamide, N-ethylmaleimide,
      and 5,5'-dithiobis(2-nitrobenzoic acid). Torsionally constrained DNA was
      assembled on the modified histones. The H3 adducts, which have no effect on the
      structure of the nucleosome, dramatically affected the structural transitions
      that the (H3-H4)2 tetrameric nucleoprotein particle can undergo. Iodoacetamide
      and N-ethylmaleimide treatment prevented the assembly of positively constrained
      DNA on the tetrameric particle, whereas 5, 5'-dithiobis(2-nitrobenzoic acid)
      treatment strongly favored it. Determination of DNA topoisomer equilibrium after
      relaxation of the tetrameric nucleoprotein particles with topoisomerase I
      demonstrated that the structural transition occurs without histone dissociation.
      Incorporation of H2A-H2B dimers into the tetrameric particle containing modified
      or unmodified cysteines allowed nucleosomes to reform and blocked the structural
      transition of the particle. We demonstrate the importance of the histone H3-H3
      contact region in the conformational changes of the histone tetramer
      nucleoprotein particle and the role of H2A-H2B in preventing a structural
      transition of the nucleosome.

PMID- 9535920
TI  - Estrogen regulation of the apolipoprotein AI gene promoter through transcription
      cofactor sharing.
AB  - Estrogen replacement therapy increases plasma concentrations of high density
      lipoprotein and its major protein constituent, apolipoprotein AI (apoAI). Studies
      with animal model systems, however, suggest opposite effects. In HepG2 cells
      stably expressing estrogen receptor alpha (ERalpha), 17beta-estradiol (E2)
      potently inhibited apoAI mRNA steady state levels. ApoAI promoter deletion
      mapping experiments indicated that ERalpha plus E2 inhibited apoAI activity
      through the liver-specific enhancer. Although the ERalpha DNA binding domain was
      essential but not sufficient for apoAI enhancer inhibition, ERalpha binding to
      the apoAI enhancer could not be detected by electrophoretic mobility shift
      assays. Western blotting and cotransfection assays showed that ERalpha plus E2
      did not influence the abundance or the activity of the hepatocyte-enriched
      factors HNF-3beta and HNF-4, two transcription factors essential for apoAI
      enhancer function. Expression of the ERalpha coactivator RIP140 dramatically
      repressed apoAI enhancer function in cotransfection experiments, suggesting that
      RIP140 may also function as a coactivator on the apoAI enhancer. Moreover,
      estrogen regulation of apoAI enhancer activity was dependent upon the balance
      between ERalpha and RIP140 levels. At low ratios of RIP140 to ERalpha, E2
      repressed apoAI enhancer activity, whereas at high ratios this repression was
      reversed. Regulation of the apoAI gene by estrogen may thus vary in direction and
      magnitude depending not only on the presence of ERalpha and E2 but also upon the
      intracellular balance of ERalpha and coactivators utilized by ERalpha and the
      apoAI enhancer.

PMID- 9535921
TI  - A keratinocyte-specific epoxygenase, CYP2B12, metabolizes arachidonic acid with
      unusual selectivity, producing a single major epoxyeicosatrienoic acid.
AB  - The CYP monooxygenase, CYP2B12, is the first identified skin-specific cytochrome
      P450 enzyme. It is characterized by high, constitutive expression in an
      extrahepatic tissue, the sebaceous glands of cutaneous tissues. It is expressed
      exclusively in a subset of differentiated keratinocytes called sebocytes, as
      demonstrated by Northern blot analysis, in situ hybridization, and polymerase
      chain reaction. The onset of its expression coincides with the morphological
      appearance of sebaceous glands in the neonatal rat. Recombinant CYP2B12 produced
      in Escherichia coli epoxidizes arachidonic acid to 11,12- and 8,9
      epoxyeicosatrienoic acids (80 and 20% of total metabolites, respectively). The
      identification of arachidonic acid as a substrate for this skin-specific CYP
      monooxygenase suggests an endogenous function in keratinocytes in the generation
      of bioactive lipids and intracellular signaling.

PMID- 9535922
TI  - Purification of a WD repeat protein, EMAP, that promotes microtubule dynamics
      through an inhibition of rescue.
AB  - The major microtubule-associated protein in echinoderms is a 77-kDa, WD repeat
      protein, called EMAP. EMAP-related proteins have been identified in sea urchins,
      starfish, sanddollars, and humans. We describe the purification of sea urchin
      EMAP and demonstrate that EMAP binding to microtubules is saturable at a molar
      ratio of 1 mol of EMAP to 3 mol of tubulin dimer. Unlike MAP-2, MAP-4, or tau
      proteins, EMAP binding to microtubules is not lost by cleavage of tubulin with
      subtilisin. In addition to binding to the microtubule polymer, EMAP binds to
      tubulin dimers in a 1:1 molar ratio. The abundance of EMAP in the egg suggests
      that it could function to regulate microtubule assembly. To test this hypothesis,
      we examined the effects of EMAP on the dynamic instability of microtubules
      nucleated from axoneme fragments as monitored by video-enhanced differential
      interference contrast microscopy. Addition of 2.2 microM EMAP to 21 microM
      tubulin results in a slight increase in the elongation and shortening velocities
      at the microtubule plus ends but not at the minus ends. Significantly, EMAP
      inhibits the frequency of rescue 8-fold without producing a change in the
      frequency of catastrophe. These results indicate that EMAP, unlike brain
      microtubule-associated proteins, promotes microtubule dynamics.

PMID- 9535923
TI  - Role of DNA in the activation of the Cry1A insecticidal crystal protein from
      Bacillus thuringiensis.
AB  - The Cry1A insecticidal crystal protein (protoxin) from six subspecies of Bacillus
      thuringiensis as well as the Cry1Aa, Cry1Ab, and Cry1Ac proteins cloned in
      Escherichia coli was found to contain 20-kilobase pair DNA. Only the N-terminal
      toxic moiety of the protoxin was found to interact with the DNA. Analysis of the
      crystal gave approximately 3 base pairs of DNA per molecule of protoxin,
      indicating that only a small region of the N-terminal toxic moiety interacts with
      the DNA. It is proposed that the DNA-protoxin complex is virus-like in structure
      with a central DNA core surrounded by protein interacting with the DNA with the
      peripheral ends of the C-terminal region extending outward. It is shown that this
      structure accounts for the unusual proteolysis observed in the generation of
      toxin in which it appears that peptides are removed by obligatory sequential
      cleavages starting from the C terminus of the protoxin. Activation of the
      protoxin by spruce budworm (Choristoneura fumiferana) gut juice is shown to
      proceed through intermediates consisting of protein-DNA complexes. Larval trypsin
      initially converts the 20-kilobase pair DNA-protoxin complex to a 20-kilobase
      pair DNA-toxin complex, which is subsequently converted to a 100-base pair DNA
      toxin complex by a gut nuclease and ultimately to the DNA-free toxin.

PMID- 9535924
TI  - Dependence of the Ca2+-inhibitable adenylyl cyclase of C6-2B glioma cells on
      capacitative Ca2+ entry.
AB  - The ability of adenylyl cyclases to be regulated by physiological transitions in
      Ca2+ provides a key point for integration of cytosolic Ca2+ concentration
      ([Ca2+]i) and cAMP signaling. Ca2+-sensitive adenylyl cyclases, whether
      endogenously or heterologously expressed, require Ca2+ entry for their
      regulation, rather than Ca2+ release from intracellular stores (Chiono, M.,
      Mahey, R., Tate, G., and Cooper, D. M. F. (1995) J. Biol. Chem. 270, 1149-1155;
      Fagan, K., Mahey, R., and Cooper, D. M. F. (1996) J. Biol. Chem. 271, 12438
      12444). The present study compared the regulation by capacitative Ca2+ entry
      versus ionophore-mediated Ca2+ entry of an endogenously expressed Ca2+
      inhibitable adenylyl cyclase in C6-2B cells. Even in the face of a dramatic
      [Ca2+]i rise generated by ionophore, Ca2+ entry via capacitative Ca2+ entry
      channels was solely responsible for the regulation of the adenylyl cyclase.
      Selective efficacy of BAPTA over equal concentrations of EGTA in blunting the
      regulation of the cyclase by capacitative Ca2+ entry defined the intimacy between
      the adenylyl cyclase and the capacitative Ca2+ entry sites. This association
      could not be impaired by disruption of the cytoskeleton by a variety of
      strategies. These results not only establish an intimate spatial relationship
      between an endogenously expressed Ca2+-inhibitable adenylyl cyclase with
      capacitative Ca2+ entry sites but also provide a physiological role for
      capacitative Ca2+ entry other than store refilling.

PMID- 9535925
TI  - The Gag domain of the Gag-Pol fusion protein directs incorporation into the L-A
      double-stranded RNA viral particles in Saccharomyces cerevisiae.
AB  - The L-A double-stranded RNA virus of yeast encodes its major coat protein, Gag,
      and a Gag-Pol fusion protein made by a -1 ribosomal frameshift, a coding strategy
      used by many retroviruses. We find that cells expressing only Gag from one
      plasmid and only Gag-Pol (in frame) from a separate plasmid can support the
      propagation of M1 double-stranded RNA, encoding the killer toxin. We use this
      system to separately investigate the functions of Gag and the Gag part of Gag
      Pol. L-A contains two fusion protein molecules per particle, and although N
      terminal acetylation of Gag is essential for viral assembly, it is completely
      dispensable for function of Gag-Pol. In general, the requirements on Gag for
      viral assembly and propagation are more stringent than on the Gag part of Gag
      Pol. Finally, we directly show that it is Gag that instructs the incorporation of
      Gag-Pol into the viral particles.

PMID- 9535926
TI  - Refolding of bacteriorhodopsin from expressed polypeptide fragments.
AB  - Bacteriorhodopsin is a heptahelical membrane protein that can be refolded to the
      native state following denaturation. To analyze the in vitro folding process with
      independent structural domains, eight fragments comprising two (AB, FG), three
      (AC, EG), four (AD, DG) or five (AE, CG) of the transmembrane segments were
      produced by expression in Escherichia coli. The polypeptides were purified to
      homogeneity by solvent extraction of E. coli membranes, repeated phase
      separation, and anion-exchange chromatography employing the C-terminal tail of
      bacteriorhodopsin for adsorption. Upon reconstitution into phospholipid/detergent
      micelles pairs of complementary fragments (AB.CG, AC.DG, AD.EG, and AE.FG)
      assembled in the presence of retinal to regenerate the characteristic
      bacteriorhodopsin chromophore with high efficiency. Together with previous
      studies, these results demonstrate that the covalent connections in each of the
      six interhelical loops are dispensable for a correct association of the helices.
      The different loops, however, contribute to the stability of the folded
      structure, as shown by increased susceptibilities toward denaturation in SDS and
      at acidic pH, and decreased Schiff base pKa values for the AB.CG, AC. DG, AD.EG,
      and AE.FG complexes, compared with the intact protein. Notably, the heptahelical
      bundle structure was also generated by all possible combinations of pairs of
      overlapping fragments, containing one (AC.CG, AD.DG, AE.EG), two (AD.CG, AE.DG),
      or three (AE.CG) redundant helices. The spectral properties of the chromophores
      indicate that the retinal-binding pocket of the AC.CG, AD.CG, and AE. CG
      complexes is formed by helices A and B of the respective N-terminal fragment and
      the C-terminal CG fragment, whereas the AD. DG, AE.DG, and AE.EG complexes are
      likely to adopt a heptahelical bundle structure analogous to AD.EG. The combined
      data show that the specificity of the helix assembly of bacteriorhodopsin is
      influenced by connectivities provided by the C-D and E-F surface loops.

PMID- 9535927
TI  - The mitogen-activated protein kinase phosphatase-3 N-terminal noncatalytic region
      is responsible for tight substrate binding and enzymatic specificity.
AB  - We have reported recently that the dual specificity mitogen-activated protein
      kinase phosphatase-3 (MKP-3) elicits highly selective inactivation of the
      extracellular signal-regulated kinase (ERK) class of mitogen-activated protein
      (MAP) kinases (Muda, M., Theodosiou, A., Rodrigues, N., Boschert, U., Camps, M.,
      Gillieron, C., Davies, K., Ashworth, A., and Arkinstall, S. (1996) J. Biol. Chem.
      271, 27205-27208). We now show that MKP-3 enzymatic specificity is paralleled by
      tight binding to both ERK1 and ERK2 while, in contrast, little or no interaction
      with either c-Jun N-terminal kinase/stress activated protein kinase (JNK/SAPK) or
      p38 MAP kinases was detected. Further study revealed that the N-terminal
      noncatalytic domain of MKP-3 (MKP-3DeltaC) binds both ERK1 and ERK2, while the C
      terminal MKP-3 catalytic core (MKP-3DeltaN) fails to precipitate either of these
      MAP kinases. A chimera consisting of the N-terminal half of MKP-3 with the C
      terminal catalytic core of M3-6 also bound tightly to ERK1 but not to
      JNK3/SAPKbeta. Consistent with a role for N-terminal binding in determining MKP-3
      specificity, at least 10-fold higher concentrations of purified MKP-3DeltaN than
      full-length MKP-3 is required to inhibit ERK2 activity. In contrast, both MKP
      3DeltaN and full-length MKP-3 inactivate JNK/SAPK and p38 MAP kinases at
      similarly high concentrations. Also, a chimera of the M3-6 N terminus with the
      MKP-3 catalytic core which fails to bind ERK elicits non selective inactivation
      of ERK1 and JNK3/SAPKbeta. Together, these observations suggest that the
      physiological specificity of MKP-3 for inactivation of ERK family MAP kinases
      reflects tight substrate binding by its N-terminal domain.

PMID- 9535928
TI  - Chimeric structure of the NAD(P)+- and NADP+-dependent malic enzymes of Rhizobium
      (Sinorhizobium) meliloti.
AB  - Malic enzymes catalyze the oxidative decarboxylation of malate to pyruvate in
      conjunction with the reduction of a nicotinamide cofactor. We determined the DNA
      sequence and transcriptional start sites of the genes encoding the
      diphosphopyridine nucleotide-dependent malic enzyme (DME, EC 1.1.1.39) and the
      triphosphopyridine nucleotide-dependent malic enzyme (TME, EC 1.1.1. 40) of
      Rhizobium (Sinorhizobium) meliloti. The predicted DME and TME proteins contain
      770 and 764 amino acids, respectively, and are approximately 320 amino acids
      larger than previously characterized prokaryotic malic enzymes. The increased
      size of DME and TME resides in the C-terminal extensions which are similar in
      sequence to phosphotransacetylase enzymes (EC 2.3.1.8). Modified DME and TME
      proteins which lack this C-terminal region retain malic enzyme activity but are
      unable to oligomerize into the native state. Data base searches have revealed
      that similar chimeric malic enzymes were uniquely present in Gram-negative
      bacteria. Thus DME and TME appear to be members of a new class of malic enzyme
      characterized by the presence of a phosphotransacetylase-like domain at the C
      terminus of the protein.

PMID- 9535929
TI  - Functional analysis of human replication protein A in nucleotide excision repair.
AB  - Human replication protein A (RPA) is a three-subunit protein complex (70-, 34-,
      and 11-kDa subunits) involved in DNA replication, repair, and recombination. Both
      the 70- (p70) and 34-kDa (p34) subunits interact with Xeroderma pigmentosum group
      A complementing protein (XPA), a key protein involved in nucleotide excision
      repair. Our deletion analysis indicated that no particular domain(s) of RPA p70
      was essential for its interaction with XPA, whereas 33 amino acids from the C
      terminus of p34 (p34Delta33C) were necessary for the XPA interaction.
      Furthermore, mutant RPA lacking the p34 C terminus failed to interact with XPA,
      suggesting that p34, not p70, is primarily responsible for the interaction of RPA
      with XPA. RPA stimulated the interaction of XPA with UV-damaged DNA through an
      RPA-XPA complex on damaged DNA sites because (i) the RPA mutant lacking the C
      terminus of p34 failed to stimulate an XPA-DNA interaction, and (ii) the ssDNA
      binding domain of RPA (amino acids 296-458) was necessary for the stimulation of
      the XPA-DNA interaction. Two separate domains of p70, a single-stranded DNA
      binding domain and a zinc-finger domain, were necessary for RPA function in
      nucleotide excision repair. The mutant RPA (RPA:p34Delta33C), which lacks its
      stimulatory effect on the XPA-DNA interaction, also poorly supported nucleotide
      excision repair, suggesting that the XPA-RPA interaction on damaged DNA is
      necessary for DNA repair activity.

PMID- 9535930
TI  - Human mitogen-activated protein kinase kinase 7 (MKK7) is a highly conserved c
      Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) activated by
      environmental stresses and physiological stimuli.
AB  - We report the cloning of a novel human activator of c-Jun N-terminal kinase
      (JNK), mitogen-activated protein kinase kinase 7 (MKK7). The mRNA for MKK7 is
      widely expressed in humans and mice and encodes a 47-kDa protein (419 amino
      acids), as determined by immunoblotting endogenous MKK7 with an antibody raised
      against its N terminus. The kinase domain of MKK7 is closely related to a
      Drosophila JNK kinase dHep (69% identity) and to a newly identified ortholog from
      Caenorhabditis elegans (54% identity), and was more distantly related to MKK4,
      MKK3, and MKK6. MKK7 phosphorylated and activated JNK1 but failed to activate p38
      MAPK in co-expression studies. In hematopoietic cells, endogenous MKK7 was
      activated by treatment with the growth factor interleukin-3 (but not interleukin
      4), or by ligation of CD40, the B-cell antigen receptor, or the receptor for the
      Fc fragment of immunoglobulin. MKK7 was also activated when cells were exposed to
      heat, UV irradiation, anisomycin, hyperosmolarity or the pro-inflammatory
      cytokine tumor necrosis factor-alpha. Co-expression of constitutively active
      mutants of RAS, RAC, or CDC42 in HeLa epithelial cells or of RAC or CDC42 in
      Ba/F3 factor-dependent hematopoietic cells also activated MKK7, suggesting that
      MKK7 will be involved in many physiological pathways.

PMID- 9535931
TI  - Spinal mechanisms underlying persistent pain and referred hyperalgesia in rats
      with an experimental ureteric stone.
AB  - Spinal neurons processing information from the ureter have been characterized in
      rats 1-4 days after the implantation of an experimental ureteric stone and
      compared with those of normal rats. The effects of a conditioning noxious
      stimulation of the ureter in the presence of the hyperalgesia evoked by the
      calculosis also were examined. Extracellular recordings were performed at the T12
      L1 segments of the spinal cord. In rats with calculosis, more neurons expressed a
      ureter input (53 vs. 42% in normal rats); such cells being more likely to show
      background activity, at a higher rate than normals (6.6 +/- 1.2 vs. 3.2 +/- 0.9
      spikes/s; mean +/- SE) and increasing with the continuing presence of the stone.
      The threshold pressure for a ureteric response was higher than in normal rats (79
      +/- 5 vs. 54 +/- 4 mmHg) but the neurons failed to encode increasing intensities
      of stimulation. Thirty-five percent of the neurons with exclusively innocuous
      somatic receptive fields had a ureter input in rats with calculosis, whereas none
      were seen in normal rats. A noxious ureteric distention applied to neurons with
      ureter input evoked a complex mixture of increases and decreases in somatic
      receptive field size and/or somatic input properties markedly different from the
      generalized increases in excitability seen when such a stimulus was applied to
      normal animals. We conclude that the presence of a ureteric stone evokes
      excitability changes of spinal neurons (enhanced background activity, greater
      number of ureter-driven cells, decreased threshold of convergent somatic
      receptive fields), which likely account for the referred hyperalgesia seen in
      rats with calculosis. However, further noxious visceral input occurring in the
      presence of persistent hyperalgesia produces selective changes that cannot be
      explained by a generalized excitability increase and suggest that the mechanisms
      underlying maintenance of hyperalgesia include alteration of both central
      inhibitory and excitatory systems.

PMID- 9535932
TI  - Spinal NMDA receptor involvement in expansion of dorsal horn neuronal receptive
      field area produced by intracutaneous histamine.
AB  - Histamine elicits the sensation of itch at the site of skin application as well
      as alloknesis (itch elicited by innocuous mechanical stimuli) in a surrounding
      area in humans and expansion of the low-threshold mechanosensitive receptive
      field area of spinal wide dynamic range (WDR)-type dorsal horn neurons in rats.
      We presently tested if the histamine-evoked expansion of neuronal receptive field
      area depends on a spinal N-methyl-D-aspartate (NMDA) receptor-mediated process.
      In pentobarbital sodium-anesthetized rats, mechanical receptive field areas of
      single WDR-type dorsal horn neurons were mapped with graded von Frey filaments
      before and 10 min after intracutaneous (ic) microinjection of histamine (1
      microl; 1, 3, or 10%) at a low-threshold site within the receptive field.
      Intracutaneous microinjection of histamine evoked dose-related increases in
      firing rate, as well as a dose-dependent expansion in mean receptive field area
      10 min after 3 and 10%, but not 1%, histamine doses. When a noncompetitive or
      competitive NMDA receptor antagonist dizocilpine [MK-801; D(-)-2-amino-5
      phosphonovalerate (APV), respectively; 1 microM] was first applied topically to
      the surface of the spinal cord, there was no significant change in mean receptive
      field area after ic microinjection of 10% histamine. The mean neuronal response
      to histamine in the presence of spinal MK-801 or APV was not significantly
      different from the mean response to histamine in the absence of these drugs.
      These results suggest that spinal NMDA receptors are involved in histamine
      induced expansion of mechanical receptive field area, a neural event possibly
      involved in the development of alloknesis.

PMID- 9535933
TI  - Conopressin affects excitability, firing, and action potential shape through
      stimulation of transient and persistent inward currents in mulluscan neurons.
AB  - The molluscan vasopressin/oxytocin-related neuropeptide conopressin activates two
      persistent inward currents in neurons from the anterior lobe of the right
      cerebral ganglion of Lymnaea stagnalis that are involved in the control of male
      copulatory behavior. The low-voltage-activated (LVA) current is activated at a
      wide range of membrane potentials, its amplitude being only weakly voltage
      dependent. The high-voltage-activated (HVA) current is activated at potentials
      positive to -40 mV only and shows a steep voltage dependence. Occurrence of both
      currents varies from cell to cell, some expressing both and others only the HVA
      current. In most neurons that have the LVA current, a conopressin-independent
      persistent inward current (INSR) is found that resembles the HVA current in its
      voltage dependence. The functional importance of the LVA and HVA currents was
      studied under current-clamp conditions in isolated anterior lobe neurons. In
      cells exhibiting both current types, the effect of activation of the LVA current
      alone was investigated as follows: previously recorded LVA current profiles were
      injected into the neurons, and the effects were compared with responses induced
      by conopressin. Both treatments resulted in a strong depolarization and firing
      activity. No differences in firing frequency and burst duration were observed,
      indicating that activation of the LVA current is sufficient to evoke bursts. In
      cells exhibiting only the HVA current, the effect of conopressin on the response
      to a depolarizing stimulus was tested. Conopressin reversibly increased the
      number of action potentials generated by the stimulus, suggesting that the HVA
      current enhances excitability and counteracts accommodation. Conopressin enhanced
      action potential broadening during depolarizing stimuli in many neurons. Voltage
      clamp experiments performed under ion-selective conditions revealed the presence
      of transient sodium and calcium currents. Using the action potential clamp
      technique, it was shown that both currents contribute to the action potential.
      The calcium current, which is activated mainly during the repolarizing phase of
      the action potential, is augmented by conopressin. Thus conopressin may directly
      modulate the shape of the action potential. In summary, conopressin may act
      simultaneously on multiple inward currents in anterior lobe neurons of Lymnaea to
      affect firing activity, excitability, and action potential shape.

PMID- 9535934
TI  - Loss of rhythmically bursting neurons in rat medial septum following selective
      lesion of septohippocampal cholinergic system.
AB  - The medial septum contains cholinergic and GABAergic neurons that project to the
      hippocampal formation. A significant proportion of the septohippocampal neurons
      (SHN) exhibit a rhythmically bursting (RB) activity that is involved in the
      generation of the hippocampal theta rhythm. The neurochemical nature of septal RB
      neurons is not firmly established. To address this question, the septal unit
      activity has been recorded in rats after selective destruction of the cholinergic
      septal neurons by the immunotoxin 192 IgG-saporin. Experiments have been
      performed in urethan-anesthetized and unanesthetized rats, 14-21 days after
      lesion. Acetylcholinesterase (AChE) histochemistry revealed a near-complete loss
      of cholinergic septal neurons and of cholinergic fibers in the hippocampus. The
      recorded neurons were located in the medial septum-diagonal band of Broca area. A
      number of these neurons were identified as projecting to the hippocampus (SHN) by
      their antidromic response to the electrical stimulation of the fimbria-fornix. In
      urethan-anesthetized lesioned rats, the percentage of RB neurons decreased
      significantly as compared with controls (17 vs. 41% for SHNs and 5 vs. 19% for
      unidentified septal neurons). The axonal conduction velocity and the burst
      frequency of the SHNs that retained a RB activity were higher in lesioned as
      compared with control rats. The number of spikes per burst was lower and the
      burst duration was shorter in lesioned rats as compared with controls. The
      urethan-resistant hippocampal theta was altered both in terms of frequency and
      amplitude. In unanesthetized lesioned rats, no RB septal neurons were found
      during arousal, as compared with 25% in controls. Their number was also markedly
      reduced during paradoxical sleep (9.7 vs. 38.5%). Histochemistry in 192 IgG
      saporin-treated rats showed that RB neurons were found in areas devoid of AChE
      positive neurons but containing parvalbumine-positive (presumably GABAergic)
      neurons. These data show that RB activity is considerably reduced after selective
      lesion of the cholinergic medial septal neurons. They suggested that the large
      majority of the RB septal neurons are cholinergic and that the few neurons that
      display RB activity in lesioned rats are GABAergic.

PMID- 9535935
TI  - Control of grasp stability when humans lift objects with different surface
      curvatures.
AB  - In previous investigations of the control of grasp stability, humans manipulated
      test objects with flat grasp surfaces. The surfaces of most objects that we
      handle in everyday activities, however, are curved. In the present study, we
      examined the influence of surface curvature on the fingertip forces used when
      humans lifted and held objects of various weights. Subjects grasped the test
      object between the thumb and the index finger. The matching pair of grasped
      surfaces were spherically curved with one of six different curvatures (concave
      with radius 20 or 40 mm; flat; convex with radius 20, 10, or 5 mm) and the object
      had one of five different weights ranging from 168 to 705 g. The grip force used
      by subjects (force along the axis between the 2 grasped surfaces) increased with
      increasing weight of the object but was modified inconsistently and incompletely
      by surface curvature. Similarly, the duration and rate of force generation, when
      the grip and load forces increased isometrically in the load phase before object
      lift-off, were not influenced by surface curvature. In contrast, surface
      curvature did affect the minimum grip forces required to prevent frictional slips
      (the slip force). The slip force was smaller for larger curvatures (both concave
      and convex) than for flatter surfaces. Therefore the force safety margin against
      slips (difference between the employed grip force and the slip force) was higher
      for the higher curvatures. We conclude that surface curvature has little
      influence on grip force regulation during this type of manipulation; the moderate
      changes in slip force resulting from changes in curvature are not fully
      compensated for by changes in grip force.

PMID- 9535936
TI  - Innervation territories of single sympathetic C fibers in human skin.
AB  - Microneurography techniques were used to record action potentials from
      unmyelinated nerve fibers (C fibers) in the cutaneous fascicles of the peroneal
      nerve in healthy volunteers. C units were identified by their long latency
      responses to electrical stimulation of their terminals in the skin. Their
      responsiveness to mechanical or heat stimuli applied to the skin or to
      sympathetic reflex provocation tests was determined by transient slowing of
      conduction velocity following activation (marking technique). In a sample of 381
      C units, 59 were unresponsive to mechanical and thermal stimulation of their
      endings, but responded to sympathetic reflex provocation tests, e.g., arousal or
      deep inspiration. They were classified as sympathetic efferent units. On average,
      conduction velocities of sympathetic units were lower (0.78 +/- 0.12 m/s, mean +/
      SD) than those of mechano-heat (CMH) or mechanoresponsive (CM) afferent C units
      (0.91 +/- 0.14 m/s). Endings of most of the sympathetic units were located in the
      skin of toes or in the foot dorsum. Innervation territories of 16 sympathetic
      units were mapped by means of conditioning transcutaneous electrical stimuli.
      Twelve units had one continuous skin territory, whereas two units had two and two
      other units had three and five separate territories, respectively. The mean
      innervated area was 128 mm2 (range: 24-350 mm2). Innervation territories of
      sympathetic units were of approximately the same size in different skin regions
      on the lower leg, foot, or toes. Based on responses to whole body cooling and
      warming, two units were tentatively classified as vasoconstrictor and sudomotor
      units, respectively. Eleven units were tested for responsiveness to iontophoresis
      of acetylcholine in their innervation territories. In five of them, activity was
      induced that was not due to central reflex activity but instead due to antidromic
      activation from the peripheral terminals. Iontophoresis of saline or histamine
      was ineffective. These findings confirm the existence of excitatory cholinergic
      receptors in the terminal membrane of some sympathetic units, possibly
      sudomotors.

PMID- 9535937
TI  - Position and velocity coupling of postural sway to somatosensory drive.
AB  - Light touch contact of a fingertip to a stationary surface provides orientation
      information that enhances control of upright stance. Slight changes in contact
      force at the fingertip lead to sensory cues about the direction of body sway,
      allowing attenuation of sway. In the present study, the coupling of postural sway
      to a moving contact surface was investigated in detail. Head, center of mass, and
      center of pressure displacement were measured as the contact surface moved
      rhythmically at 0.1, 0.2, 0.4, 0.6, and 0.8 Hz. Stimulus amplitude decreased with
      frequency to maintain peak velocity constant across frequency. Head and body sway
      were highly coherent with contact surface motion at all frequencies except 0.8
      Hz, where a drop-off in coherence was observed. Mean frequency of head and body
      sway matched the driving frequency </=0.4 Hz. At higher frequencies, non-1:1
      coupling was evident. The phase of body sway relative to the touch plate averaged
      20-30 degrees at 0.1-Hz drive and decreased approximately linearly to -130
      degrees at 0.8-Hz drive. System gain was approximately 1 across frequency. The
      large phase lags observed cannot be accounted for with velocity coupling alone
      but indicate that body sway also was coupled to the position of the touch plate.
      Fitting of a linear second-order model to the data suggests that postural control
      parameters are not fixed but adapt to the moving frame of reference. Moreover,
      coupling to both position and velocity suggest that a spatial reference frame is
      defined by the somatosensory system.

PMID- 9535938
TI  - Mesolimbic component of the ascending cholinergic pathways: electrophysiological
      pharmacological study.
AB  - The cholinergic input from the pontomesencephalic cholinergic neurons to the
      diencephalic and basal forebrain structures has been implicated in a number of
      limbically controlled overt behaviors. The cellular mechanism by which the
      cholinergic terminals initiate behavioral manifestations is not clear. The
      objective of this study was to investigate the effects of the ascending
      cholinergic projection from the laterodorsal tegmental nucleus (LDT) on neuronal
      firing in the anterior hypothalamic-medial preoptic region (AHMP), known to be
      involved in agonistic behavior. Experiments were performed on urethan
      anesthetized rats. Iontophoretic application of carbachol (CCh) into the vicinity
      of single cells in the AHMP caused a dose-dependent decrease in the mean firing
      rate of 83% of units and an increase in 10% of units. The inhibitory effect of
      CCh, but not the excitatory effect, was reversed by iontophoretic pretreatment
      with scopolamine. The inhibition of the firing rate was repeatable for the same
      dose of CCh and dose dependent. Electrical stimulation of neurons in the LDT
      caused a comparable, current-dependent decrease in the mean firing rate of AHMP
      neurons that also was reversed by pretreatment of neurons in the AHMP with
      scopolamine. The antagonizing effects of scopolamine were reversible with time.
      The same units in the AHMP that inhibited their firing to stimulation of the LDT
      also responded with a similar inhibition to local iontophoretic CCh. Finally, the
      fluorescent carbocyanine dye, 4-(4-(dihexadecylamino)styryl)-N-methylpyridinium
      iodide, (DiA), has been used as a retrograde axonal tracer and was injected into
      the recording sites immediately after the electrophysiological recordings. After
      1 wk, DiA dye was found in numerous neurons in the LDT as shown by the
      fluorescence confocal microscopy. Results of the study suggest that LDT
      cholinergic neurons project and terminate in the AHMP and that their activation
      causes a decrease in the mean firing rate of the AHMP neurons. It is postulated
      that this inhibitory effect is implicated in the initiation of some of the
      behavioral patterns like defensive or alarm vocalization and behavioral
      inhibition.

PMID- 9535939
TI  - Forms of forward quadrupedal locomotion. II. A comparison of posture, hindlimb
      kinematics, and motor patterns for upslope and level walking.
AB  - To gain insight into the neural mechanisms controlling different forms of
      quadrupedal walking of normal cats, data on postural orientation, hindlimb
      kinematics, and motor patterns of selected hindlimb muscles were assessed for
      four grades of upslope walking, from 25 to 100% (45 degrees incline), and
      compared with similar data for level treadmill walking (0.6 m/s). Kinematic data
      for the hip, knee, ankle, and metatarsophalangeal joints were obtained from
      digitizing cine film that was synchronized with electromyographic (EMG) records
      from 13 different hindlimb muscles. Cycle periods, the structure of the step
      cycle, and paw-contact sequences were similar at all grades and typical of
      lateral-sequence walking. Also, a few half-bound and transverse gallop steps were
      assessed from trials at the 100% grade; these steps had shorter cycle periods
      than the walking steps and less of the cycle (68 vs. 56%) was devoted to stance.
      Each cat assumed a crouched posture at the steeper grades of upslope walking and
      stride length decreased, whereas the overall position of the stride shifted
      caudally with respect to the hip joint. At the steeper grades, the range and
      duration of swing-related flexion increased at all joints, the stance-phase yield
      was absent at the knee and ankle joints, and the range of stance-phase extension
      at knee and ankle joints increased. Patterns of muscle activity for upslope and
      level walking were similar with some notable exceptions. At the steeper grades,
      the EMG activity of muscles with swing-related activity, such as the digit flexor
      muscle, the flexor digitorum longus (FDL), and the knee flexor muscle, the
      semitendinosus (ST), was prolonged and continued well into midswing. The EMG
      activity of stance-related muscles also increased in amplitude with grade, and
      three muscles not active during the stance phase of level walking had stance
      activity that increased in amplitude and duration at the steepest grades; these
      muscles were the ST, FDL, and extensor digitorum brevis. Overall the changes in
      posture, hindlimb kinematics, and the activity patterns of hindlimb muscles
      during upslope walking reflected the need to continually move the body mass
      forward and upward during stance and to ensure that the paw cleared the inclined
      slope during swing. The implications of these changes for the neural control of
      walking and expected changes in hindlimb kinetics for slope walking are
      discussed.

PMID- 9535940
TI  - Forms of forward quadrupedal locomotion. III. A comparison of posture, hindlimb
      kinematics, and motor patterns for downslope and level walking.
AB  - To gain further insight into the neural mechanisms for different forms of
      quadrupedal walking, data on postural orientation, hindlimb kinematics, and motor
      patterns were assessed for four grades of downslope walking, from 25% (14 degrees
      slope) to 100% (45 degrees), and compared with data from level and downslope
      walking at five grades (5-25%) on the treadmill (0.6 m/s). Kinematic data were
      obtained by digitizing cine film, and electromyograms (EMGs) synchronized with
      kinematic records were taken from 13 different hindlimb muscles. At grades from
      25 to 75%, cycle periods were similar, but at the steepest grade the cycle was
      shorter because of a reduced stance phase. Paw-contact sequences at all grades
      were consistent with lateral-sequence walking, but pace walking often occurred at
      the steepest grades. The cats crouched at the steeper grades, and crouching was
      associated with changes in fore- and hindlimb orientation that were consistent
      with increasing braking forces and decreasing propulsive forces during stance.
      The average ranges of motion at the hindlimb joints, except at the hip, were
      often different at the two steepest slopes. During swing, the range of knee- and
      ankle-joint flexion decreased, and the range and duration of extension increased
      at the ankle joint to lower the paw downward for contact. During stance the range
      of flexion during yield increased at the ankle joint, and the range of extension
      decreased at the knee and metatarsophalangeal joints. Downslope walking was also
      associated with EMG changes for several muscles. The hip extensors were not
      active during stance; instead, hip flexors were active, presumably to slow the
      rate of hip extension. Although ankle extensors were active during stance, their
      burst durations were truncated and centered around paw contact. Ankle flexors
      were active after midstance at the steeper slopes before the need to initiate
      swing, whereas flexor and extensor digit muscles were coactive throughout stance.
      Overall the changes in posture, hindlimb kinematics, and activity patterns of
      hindlimb muscles during stance reflected a need to counteract external forces
      that would accelerate angular displacements at some joints. Implications of these
      changes are discussed by using current models for the neural control of walking.

PMID- 9535941
TI  - Primary somatosensory cortical neuronal activity during monkey's detection of
      perceived change in tooth-pulp stimulus intensity.
AB  - To elucidate the functional properties of primary somatosensory cortical neurons
      for the perception of tooth-pulp sensation, neuronal activity was recorded from
      the primary somatosensory cortex (SI) in awake behaving monkeys. Monkeys were
      trained to detect changes in tooth-pulp stimulus intensity applied to the upper
      canine or incisor tooth pulp. Stimulus intensities applied to the tooth pulp were
      multiples of the threshold intensity for the jaw opening reflex (1.0 T) elicited
      by tooth-pulp stimulation. When monkeys pressed a button, baseline electrical
      pulses (V1: 0.5 T, 1.0 T, 2.0 T, or 3.0 T) were applied to the tooth pulp. After
      4-8 s, a V2 stimulus (0.3 T, 0.5 T, 1.0 T, or 2.0 T) was added to V1. Percent
      escapes at V1 stimulus intensity of 0.5 T and 1.0 T were approximately 10%, 22%
      at 2.0 T, and 40% at 3.0 T (total of 1,997 trials). A total of 862 single units
      were recorded from the SI. Thirty-seven SI neurons responded to electrical
      stimulation of the tooth pulp (tooth-pulp-driven neurons; TPNs), 139 SI neurons
      responded to tactile stimulation of the lateral face area, 90 to upper lip and 99
      to lower lip, 44 to tongue and 102 to periodontal membrane, whereas 351 SI
      neurons were not responsive to tactile stimulation of the orofacial regions.
      Thirty of 37 TPNs were recorded long enough to test with V1 stimuli ranging from
      0.5 T to 3.0 T. Eleven of 30 TPNs linearly increased their firing frequency
      following increases in stimulus intensity (encoding TPNs), whereas 19 did not
      (nonencoding TPNs). Mean first spike latency of encoding TPNs was 24.8 +/- 1.7 ms
      (n = 11), that of nonencoding TPNs was 23.6 +/- 1.5 ms (n = 19), and that of
      unclassified TPNs was 24.7 +/- 3.7 ms (n = 7). TPNs were distributed in the areas
      1-2, 3a, and 3b within the oral projection area and the transition zone between
      the face and oral projection areas of the SI. All of them received inputs from
      the intraoral structures, facial skin, or both. The firing frequency of eight
      encoding and nonencoding TPNs was correlated with detection latency at stimulus
      intensities of 0.5 and 1.0 T. On the other hand, when the baseline stimulus was
      increased to 2.0 T and 3.0 T, the discharge of most TPNs did not increase in
      firing frequency with the reduction in detection latency. These results indicate
      that the discharge rates of some SI TPNs are correlated with detection latency at
      near-noxious threshold and noxious stimulus intensities. These findings suggest
      that some TPNs are involved in the sensory-discriminative aspect of tooth-pulp
      sensation in the near-pain threshold and pain ranges.

PMID- 9535942
TI  - Enhanced propagation of epileptiform activity through the kindled dentate gyrus.
AB  - Extracellular recordings were performed in combined hippocampal-entorhinal cortex
      (HC-EC) slices obtained from control and commissural kindled rats to investigate
      the propagation of epileptiform activity from the entorhinal cortex (EC) to the
      hippocampus (HC) after chronic epilepsy. Lowering extracellular Mg2+
      concentration in control slices induced epileptiform activity consisting of
      spontaneous epileptiform bursts in area CA3 and of electrographic seizures in the
      EC. In contrast, the CA3 region of HC-EC slices obtained from kindled rats
      displayed significantly longer lasting epileptiform bursts and electrographic
      seizures. The electrographic seizures that were absent in controls propagated
      from the EC because disconnecting the HC from the EC stopped their occurrence in
      the CA3, whereas epileptiform bursts persisted with an unaltered pattern and
      frequency. Thus the area CA3 is affected by kindling and contributes to the
      spread of epileptiform activity within the EC-HC complex. We developed a method
      to induce focal epileptiform activity in the EC by locally perfusing the gamma
      aminobutyric acid-A (GABA) antagonist bicuculline (50 mM) in 10 mM KCl containing
      artificial cerebrospinal fluid. This method enabled us to investigate the
      propagation of epileptiform discharges from the disinhibited EC to the DG without
      affecting the DG with the epileptogenic medium. We show here that kindling
      facilitates the propagation of epileptiform activity through the DG. These data
      are consistent with the normal function of the DG as a filter limiting the spread
      of epileptiform activity within the HC-EC complex. This gating mechanism breaks
      down after chronic epilepsy induced by kindling.

PMID- 9535943
TI  - Glucose-induced intracellular ion changes in sugar-sensitive hypothalamic
      neurons.
AB  - In the lateral hypothalamic area (LHA) of rat brain, approximately 30% of cells
      showed sensitivity to small changes in local concentrations of glucose. These
      "glucose-sensitive" neurons demonstrated four types of behavior, three of which
      probably represent segments of a continuous spectrum of recruitment in response
      to ever more severe changes in blood sugar. Type I cells showed maximum activity
      </=5.6 mM blood glucose but became completely silent at hyperglycemia of 10-12 mM
      (normoglycemia 7.6 +/- 0.3 mM; mean +/- SD). Type II and III neurons exhibited a
      wider range of response. Type IV cells (5-7% of glucose-sensitive neurons)
      paralleled the behavior of sugar-sensitive cells in ventromedial hypothalamic
      nucleus (VMH). In VMH, approximately 40% of cells responded to changes in blood
      glucose over a range of concentrations from 3.6 to 17 mM, by increasing their
      firing rate as sugar level rose and vice versa. Ionic shifts during increases in
      blood (brain) glucose levels were similar in LHA types I-III but fastest in I and
      slowest in III. [Na+]i fell by 5-9 mM, [K+]i rose by 6-8 mM, and plasma membrane
      hyperpolarized by 5 mV. [Ca2+]i declined by 15-20 nM in line with membrane
      hyperpolarization. In VMH and type IV LHA cells, [K+]i fell 3-8 mM and plasma
      membrane depolarized -3 to -5 mV as blood/brain glucose concentration increased
      from 7.6/2.4 to 17.6/4.2 mM, whereas [Ca2+]i increased from 125 to 180 nM as a
      consequence of falling membrane potential. During falls in blood/brain sugar
      concentration the effects in both VMH and LHA cells were reversed. The findings
      are consistent with the ionic shifts in types I-III LHA cells being dependent on
      alterations in Na/K-ATPase activity, whereas those in VMH and type IV LHA cells
      could be caused by modulation of ATP-dependent K+ channels. A possible mechanism
      for linking the effects of small changes in glucose to ATP generation, which
      could bring about the above phenomena, is the interposition of a "glucokinase
      type" enzyme in a role similar to that which it has in glucose-sensing pancreatic
      beta-cells.

PMID- 9535944
TI  - Complex blockade of TTX-resistant Na+ currents by lidocaine and bupivacaine
      reduce firing frequency in DRG neurons.
AB  - Mechanisms of blockade of tetrodotoxin-resistant (TTXr) Na+ channels by local
      anesthetics in comparison with the sensitivity of tetrodotoxin-sensitive (TTXs)
      Na+ channels were studied by means of the patch-clamp technique in neurons of
      dorsal root ganglions (DRG) of rat. Half-maximum inhibitory concentration (IC50)
      for the tonic block of TTXr Na+ currents by lidocaine was 210 micromol/l, whereas
      TTXs Na+ currents showed five times lower IC50 of 42 micromol/l. Bupivacaine
      blocked TTXr and TTXs Na+ currents more potently with IC50 of 32 and 13
      micromol/l, respectively. In the inactivated state, TTXr Na+ channel block by
      lidocaine showed higher sensitivities (IC50 = 60 micromol/l) than in the resting
      state underlying tonic blockade. The time constant tau1 of recovery of TTXr Na+
      channels from inactivation at -80 mV was slowed from 2 to 5 ms after addition of
      10 micromol/l bupivacaine, whereas the tau2 value of approximately 500 ms
      remained unchanged. The use-dependent block of TTXr Na+ channels led to a
      progressive reduction of current amplitudes with increasing frequency of
      stimulation, which was </=53% block at 20 Hz in 10 micromol/l bupivacaine and 81%
      in 100 micromol lidocaine. The functional importance of the use-dependent block
      was confirmed in current-clamp experiments where 30 micromol/l of lidocaine or
      bupivacaine did not suppress the single action potential but clearly reduced the
      firing frequency of action potentials again with stronger potency of bupivacaine.
      Because it was found that TTXr Na+ channels predominantly occur in smaller
      sensory neurons, their blockade might underlie the suppression of the sensation
      of pain. Different sensitivities and varying proportions of TTXr and TTXs Na+
      channels could explain the known differential block in spinal anesthesia. We
      suggest that the frequency reduction at low local anesthetic concentrations may
      explain the phenomenon of paresthesia where sensory information are suppressed
      gradually during spinal anesthesia.

PMID- 9535945
TI  - Vowel representations in the ventral cochlear nucleus of the cat: effects of
      level, background noise, and behavioral state.
AB  - Single-unit responses were studied in the ventral cochlear nucleus (VCN) of cats
      as formant and trough features of the vowel /epsilon/ were shifted in the
      frequency domain to each unit's best frequency (BF; the frequency of greatest
      sensitivity). Discharge rates sampled with this spectrum manipulation procedure
      (SMP) were used to estimate vowel representations provided by populations of VCN
      neurons. In traditional population measures, a good representation of a vowel's
      formant structure is based on relatively high discharge rates among units with
      BFs near high-energy formant features and low rates for units with BFs near low
      energy spectral troughs. At most vowel levels and in the presence of background
      noise, chopper units exhibited formant-to-trough rate differences that were
      larger than VCN primary-like units and auditory-nerve fibers. By contrast, vowel
      encoding by primary-like units resembled auditory nerve representations for most
      stimulus conditions. As is seen in the auditory nerve, primary-like units with
      low spontaneous rates (SR <18 spikes/s) produced better representations than high
      SR primary-like units at all but the lowest vowel levels. Awake cats exhibited
      the same general response properties as anesthetized cats but larger between
      subject differences in vowel driven rates. The vowel encoding properties of VCN
      chopper units support previous interpretations that patterns of auditory nerve
      convergence on cochlear nucleus neurons compensate for limitations in the dynamic
      range of peripheral neurons.

PMID- 9535946
TI  - Modulation of synaptic transmission by dopamine and norepinephrine in ventral but
      not dorsal striatum.
AB  - Although the ventral striatum (nucleus accumbens; NAc) and dorsal striatum are
      associated with different behaviors, these structures are anatomically and
      physiologically similar. In particular, dopaminergic afferents from the midbrain
      appear to be essential for the normal functioning of both nuclei. Although a
      number of studies have examined the effects of dopamine on the physiology of NAc
      or striatal cells, results have varied, and few studies have compared directly
      the actions of dopamine on both of these nuclei. Here we use slice preparations
      of the NAc and dorsal striatum to compare how synaptic transmission in these
      nuclei is modulated by catecholamines. As previously reported, dopamine depressed
      excitatory postsynaptic potentials (EPSPs) and inhibitory postsynaptic potentials
      (IPSPs) in the NAc. Surprisingly, however, neither EPSPs nor IPSPs in the dorsal
      striatum were affected by dopamine. Similarly, norepinephrine depressed
      excitatory synaptic transmission in the NAc by an alpha-adrenergic receptor
      dependent mechanism but was without effect on excitatory transmission in the
      dorsal striatum. Inhibitory synaptic transmission was not affected by
      norepinephrine in either structure. These results suggest that the functional
      roles of dopamine and norepinephrine are not the same in the dorsal striatum and
      the NAc.

PMID- 9535947
TI  - Distribution and characteristics of poststimulus effects in proximal and distal
      forelimb muscles from red nucleus in the monkey.
AB  - We used stimulus-triggered averaging (StTA) of electromyographic (EMG) activity
      to investigate two major questions concerning the functional organization of the
      magnocellular red nucleus (RNm) for reaching movements in the macaque monkey. The
      first is whether the clear preference toward facilitation of extensor muscles we
      have reported in previous studies for distal (wrist and digit) forelimb muscles
      also exists for proximal muscles (shoulder and elbow). The second question is
      whether distal and proximal muscles may be cofacilitated from RNm suggesting the
      representation of functional muscle synergies for coordinated reaching movements.
      Two monkeys were trained to perform a prehension task requiring multijoint
      coordination of the forelimb. EMG activity was recorded from 24 forelimb muscles
      including 5 shoulder, 7 elbow, 5 wrist, 5 digit, and 2 intrinsic hand muscles.
      Microstimulation (20 microA at 20 Hz) was delivered throughout the movement task.
      From 137 microstimulation sites in the RNm, a total of 977 poststimulus effects
      was obtained including 733 poststimulus facilitation effects (PStF) and 244
      poststimulus suppression effects (PStS). Of the PStF effects, 58% were obtained
      from distal muscles; 42% from proximal muscles. Digit muscles were more
      frequently facilitated (35%) than the wrist, elbow, or shoulder muscles (20, 24,
      and 18%, respectively). The intrinsic hand muscles were infrequently facilitated
      (3%). At all joints tested, PStF was more common in extensor muscles than flexor
      muscles. This extensor preference was very strong for shoulder (85%), wrist
      (85%), and digit muscles (94%) and weaker for elbow muscles (60%). Of the PStS
      effects, 65% were in distal muscles and 35% in proximal muscles. Interestingly,
      the flexor muscles were more frequently inhibited from RNm than extensor muscles.
      At 72% of stimulation sites, at least two muscles were facilitated. The majority
      of these sites (61%) cofacilitated both proximal and distal muscles. At the
      remaining sites (39%), PStF was observed in either the proximal (17%) or distal
      muscles (22%). Facilitation most often involved combinations of shoulder, elbow,
      and distal muscles (30%) or shoulder and distal muscles (26%). Only rarely were
      intrinsic hand muscles part of the total muscle synergy. Our results show that
      the RNm 1) controls both proximal and distal muscles but the strength of
      influence is biased toward distal muscles, 2) preferentially controls extensor
      muscles not only at distal forelimb joints but also at proximal joints, and 3)
      output zones cofacilitate synergies of proximal and distal muscles involved in
      the control of forelimb reaching movements.

PMID- 9535948
TI  - Prenatal dietary choline supplementation decreases the threshold for induction of
      long-term potentiation in young adult rats.
AB  - Choline supplementation during gestation in rats leads to augmentation of spatial
      memory in adulthood. We hypothesized that prenatal (E12-E17) choline
      supplementation in the rat would lead to an enhancement of hippocampal synaptic
      plasticity as assessed by long-term potentiation (LTP) at 3-4 mo of age. LTP was
      assessed blindly in area CA1 of hippocampal slices with first suprathreshold
      (above threshold for LTP generation in control slices) theta-burst stimulus
      trains. The magnitude of potentiation after these stimuli was not different
      between slices from control and prenatally choline supplemented animals. Next,
      threshold (reliably leading to LTP generation in control slices) or subthreshold
      theta-burst stimulus trains were applied to slices from control, prenatally
      choline-supplemented, and prenatally choline-deprived rats. Threshold level
      stimulus trains induced LTP in slices from both the control and choline
      supplemented rats but not in those from the choline-deficient rats. Subthreshold
      stimulus trains led to LTP induction in slices from prenatally choline
      supplemented rats only. These observations indicate that prenatal dietary
      manipulation of the amino acid, choline, leads to subsequent significant
      alterations of LTP induction threshold in adult animals.

PMID- 9535949
TI  - Information about spatial view in an ensemble of primate hippocampal cells.
AB  - Hippocampal function was analyzed by making recordings from hippocampal neurons
      in monkeys actively walking in the laboratory. "Spatial view" cells, which
      respond when the monkey looks at a part of the environment, were analyzed. To
      assess quantitatively the information about the spatial environment represented
      by these cells, we applied information theoretic techniques to their responses.
      The average information provided by these cells about which location the monkey
      was looking at was 0.32 bits, and the mean across cells of the maximum
      information conveyed about which location was being looked at was 1.19 bits,
      measured in a period of 0.5 s. There were 16 locations for this analysis, each
      being one-quarter of one of the walls of the room. It also was shown that the
      mean spontaneous rate of firing of the neurons was 0.1 spikes/s, that the mean
      firing rate in the center of the spatial field of the neurons was 13.2 spikes/s,
      and that the mean sparseness of the representation measured in a 25-ms period was
      0.04 and in a 500-ms time period was 0.19. (The sparseness is approximately
      equivalent to the proportion of the 25- or 500-ms periods in which the neurons
      showed one or more spikes.) Next it was shown that the mean size of the view
      fields of the neurons was 0.9 of a wall. In an approach to the issue of how an
      ensemble of neurons might together provide more precise information about spatial
      location than a single neuron, it was shown that in general the neurons had
      different centers for their view fields. It then was shown that the information
      from an ensemble of these cells about where in space is being looked at increases
      approximately linearly with the number of cells in the ensemble. This indicates
      that the number of places that can be represented increases approximately
      exponentially with the number of cells in the population. It is concluded that
      there is an accurate representation of space "out there" in the primate
      hippocampus. This representation of space out there would be an appropriate part
      of a primate memory system involved in memories of where in an environment an
      object was seen, and more generally in the memory of particular events or
      episodes, for which a spatial component normally provides part of the context.

PMID- 9535951
TI  - Temporal and amplitude generalization in motor learning.
AB  - A fundamental feature of human motor control is the ability to vary effortlessly
      over a substantial range, both the duration and amplitude of our movements. We
      used a three-dimensional robotic interface, which generated novel velocity
      dependent forces on the hand, to investigate how adaptation to these altered
      dynamics experienced only for movements at one temporal rate and amplitude
      generalizes to movements made at a different rate or amplitude. After subjects
      had learned to make a single point-to-point movement in a novel velocity
      dependent force field, we examined the generalization of this learning to
      movements of both half the duration or twice the amplitude. Such movements
      explore a state-space not experienced during learning-any changes in behavior are
      due to generalization of the learning, the form of which was used to probe the
      intrinsic constraints on the motor control process. The generalization was
      assessed by determining the force field in which subjects produced kinematically
      normal movements. We found substantial generalization of the motor learning to
      the new movements supporting a nonlocal representation of the control process. Of
      the fields tested, the form of the generalization was best characterized by
      linear extrapolation in a state-space representation of the controller. Such an
      intrinsic constraint on the motor control process can facilitate the scaling of
      natural movements.

PMID- 9535952
TI  - Plasticity in an electrosensory system. III. Contrasting properties of spatially
      segregated dendritic inputs.
AB  - Efferent neurons of the first-order electrosensory processing center of the
      brain, the electrosensory lateral line lobe (ELL), receive electroreceptor
      afferent input as well as feedback inputs descending from higher centers. These
      ELL efferents, pyramidal cells, adaptively filter predictable patterns of sensory
      input while preserving sensitivity to novel stimuli. The filter mechanism
      involves integration of centrally generated predictive inputs with the afferent
      inputs being canceled. The predictive inputs, referred to as "negative image"
      inputs, terminate on pyramidal cell apical dendrites and generate responses that
      are opposite those resulting from the predictable afference, hence integration of
      these signals results in attenuation of pyramidal cell responses. The system also
      shows a robust form of plasticity; the pyramidal cells learn, with a time course
      of a few minutes, to cancel new patterns of repetitive inputs. This is
      accomplished by adjusting the strength of excitatory and inhibitory apical
      dendritic inputs according to an anti-Hebbian learning rule. This study focuses
      on the properties of two separate pathways that convey descending information to
      pyramidal cell apical dendrites. One pathway terminates proximally, nearer to the
      pyramidal cell body, whereas the other terminates distally. Recordings of ELL
      evoked potentials, extracellular pyramidal cell spike responses, and
      intracellularly recorded synaptic potentials show that the pyramidal cells
      respond oppositely to moderate-frequency (> approximately 8 Hz) single pulse
      stimulation or repeated (1/s) tetanic activation of these two pathways.
      Repetitive activation of the proximally terminating pathway results in highly
      facilitating responses due to potentiation of pyramidal cell excitatory
      postsynaptic potentials (EPSPs). These same stimuli applied to the distally
      terminating pathway result in a reduction of pyramidal cell responses due to
      depression of EPSPs and potentiation of inhibitatory postsynaptic potentials
      (IPSPs). Anti-Hebbian plasticity was demonstrated by pairing tetanic stimulation
      of either pathway with changes in the postsynaptic cell's membrane potential.
      After stabilization of the response potentiation due to tetanic stimulation of
      the proximally terminating pathway, paired postsynaptic hyperpolarization
      resulted in further increases in spike responses and additional potentiation of
      pyramidal cell EPSPs. Paired postsynaptic depolarization reduced subsequent
      responses to the tetanus, depressed EPSP amplitudes, and, in many cases,
      potentiated IPSPs. The same pattern of plasticity was observed when postsynaptic
      hyper- or depolarization was paired with tetanic stimulation of the distally
      terminating pathway except that the plasticity was superimposed on the depressed
      pyramidal cell responses resulting from stimulating this pathway alone.
      Modulation of a postsynaptic form of synaptic depression is proposed to account
      for the anti-Hebbian plasticity associated with both pathways.

PMID- 9535950
TI  - Morphologically identified cutaneous afferent DRG neurons express three different
      potassium currents in varying proportions.
AB  - Outward K+ currents were recorded using a whole cell patch-clamp configuration,
      from acutely dissociated adult rat cutaneous afferent dorsal root ganglion (DRG)
      neurons (L4 and L5) identified by retrograde labeling with Fluoro-gold.
      Recordings were obtained 16-24 h after dissociation from cells between 39 and 49
      mm in diameter with minimal processes. These cells represent medium-sized DRG
      neurons relative to the entire population, but are large cutaneous afferent
      neurons giving rise to myelinated axons. Voltage-activated K+ currents were
      recorded routinely during 300-ms depolarizing test pulses increasing in 10-mV
      steps from -40 to +50 mV; the currents were preceded by a 500-ms conditioning
      prepulse of either -120 or -40 mV. Coexpression of at least three components of
      K+ current was revealed. Separation of these components was achieved on the basis
      of sensitivities to the K+ channel blockers, 4-aminopyridine (4-AP) and
      dendrotoxin (DTx), and by the current responses to variation in conditioning
      voltage. Changing extracellular K+ concentration from 3 to 40 mM resulted in a
      shift to the right of the I-V curve commensurate with K+ being the principal
      charge carrier. Presentation of 100 mM 4-AP revealed a rapidly activating K+
      current sensitive to low concentrations of 4-AP. High concentrations of 4-AP (6
      mM) extinguished all inactivating current, leaving almost pure sustained current
      (IK). On the basis of the relative distribution of K+ currents neurons could be
      separated into three distinct categories: fast inactivating current (IA), slow
      inactivating current (ID), and sustained current (IK); only IA and IK; and slow
      inactivating current and IK. However, IK was always the dominant outward current
      component. These results indicate that considerable variation in K+ currents is
      present not only in the entire population of DRG neurons, as previously reported,
      but even within a restricted size and functional group (large cutaneous afferent
      neurons).

PMID- 9535953
TI  - New look at force-frequency relationship of human skeletal muscle: effects of
      fatigue.
AB  - A muscle does not have a unique force-frequency relationship; rather, it is
      dynamic and depends on the activation history of muscle. The purpose of this
      study was to investigate the force-frequency relationship of nonfatigued and
      fatigued skeletal muscle with the use of both catchlike-inducing trains (CITs)
      that exploited the catchlike property of skeletal muscle and constant-frequency
      trains (CFTs). Quadriceps femoris muscles were studied during isometric
      contractions in twelve healthy subjects (5 females, 7 males). Both the peak force
      and force-time integrals produced in response to each stimulation train were
      analyzed. Compared with nonfatigued muscles, higher frequencies of activation
      were needed to produce comparable normalized peak forces when the muscles were
      fatigued (i.e., a "rightward" shift in the force-frequency relationship) for both
      the CFTs and the CITs. When using the normalized force-time integral to measure
      muscle performance, the CFTs required slightly higher frequencies to produce
      comparable normalized forces from fatigued muscles, but the CITs did not.
      Furthermore, when the muscles were fatigued, the CITs produced greater peak
      forces and force-time integrals than all comparable CFTs with frequencies </=20
      pps. In general, the lower the frequency the greater the augmentation produced by
      the CITs. In addition, the CIT that elicited the greatest force-time integral
      produced a 25% greater force-time integral than the best CFT. Because the CITs
      augmented forces across a wide range of physiological relevant activation rates,
      these results may have important clinical implications when using electrical
      stimulation to aid patients with paralysis. The results of this study contribute
      to our understanding of the relationship between the activation pattern of a
      muscle and the force output produced.

PMID- 9535954
TI  - Synchronous period-doubling in flicker vision of salamander and man.
AB  - Periodic flashes of light have long served to probe the temporal properties of
      the visual system. Here we show that during rapid flicker of high contrast and
      intensity the eye reports to the brain only every other flash of light. In this
      regime, retinal ganglion cells of the salamander fire spikes on alternating
      flashes. Neurons across the entire retina are locked to the same flashes. The
      effect depends sharply on contrast and flash frequency. It results from a period
      doubling bifurcation in retinal processing, and a simple model of nonlinear
      feedback reproduces the phenomenon. Pharmacological studies indicate that the
      critical feedback interactions require only cone photoreceptors and bipolar
      cells. Analogous period-doubling is observed in the human visual system. Under
      bright full-field flicker, the electroretinogram (ERG) shows a regime of period
      doubling between 30 and 70 Hz. In visual evoked potentials from the occiput, the
      subharmonic component is even stronger. By analyzing the accompanying perceptual
      effects, we find that retinal period-doubling begins in the periphery of the
      visual field, and that it is the cause of a long mysterious illusory flicker
      pattern.

PMID- 9535955
TI  - Noise-induced tuning curve changes in mechanoreceptors.
AB  - Fibers from the tibial nerve of rat were isolated and spike activity recorded
      using monopolar hook electrodes. The receptive field (RF) of each recorded unit
      on the glabrous skin of the foot was mechanically stimulated with waveforms
      comprised of various frequency sine waves in addition to increasing levels of
      white noise. Single-unit responses were recorded for both rapidly adapting (RA)
      and slowly adapting (SA) units. Signal-to-noise ratio (SNR) of the output was
      quantified by the correlation coefficient (C1) between the input sine wave and
      the nerve responses. The addition of noise enhanced signal transmission in both
      RA and SA fibers. With increasing noise, the initially inverted "V"-shaped, zero
      noise tuning curves for RA fibers broadened and eventually inverted. There was a
      large expansion of the frequencies that the RA receptor responded to with
      increasing noise input. On the other hand, the typical shape of the SA fiber
      tuning curves remained invariant, at all noise levels tested. C1 values continued
      to increase with larger noise input for higher frequencies, but did not do so at
      the lowest frequencies. For both RA and SA fibers the responses with added noise
      tended to be rate modulated at the low-frequency end, and followed nonlinear
      stochastic resonance (SR) properties at the higher frequencies. The changes in
      the tuning properties due to noise found here, as well as preliminary
      psychophysics data, imply that external noise is relevant for sensing small
      periodic signals in the environment. All current models of sensory perception
      assume that the tuning properties of receptors determined in the absence of noise
      are preserved during everyday tasks. Our results indicate that this is not true
      in a noisy environment.

PMID- 9535956
TI  - Kinetic analysis of glycine receptor currents in ventral cochlear nucleus.
AB  - Glycine plays an important role as an inhibitory neurotransmitter in the ventral
      cochlear nucleus. However, little is known about the kinetic behavior of glycine
      receptors. The present study examines the kinetics of the native inhibitory
      glycine receptors in neurons of the ventral cochlear nucleus, using outside-out
      patches from acutely dissociated cells and a fast flow system. Steps into 1 mM
      glycine revealed fast phases of desensitization with time constants of 13 and 129
      ms, that together produced a 40% reduction in current from the peak response.
      Slower desensitization phases also were observed. After removal of glycine,
      currents deactivated with two time constants of 15 and 68 ms, and these rates
      were independent of the glycine concentration between 0.2 and 1 mM. Recovery from
      desensitization was slow relative to desensitization itself. These results
      demonstrate that glycine receptors can exhibit faster rates of desensitization
      and deactivation than previously reported.

PMID- 9535957
TI  - Dendritic structure and receptive-field organization of optic flow processing
      interneurons in the fly.
AB  - The third visual neuropil (lobula plate) of the blowfly Calliphora erythrocephala
      is a center for processing motion information. It contains, among others, 10
      individually identifiable "vertical system" (VS) neurons responding to visual
      wide-field motions of arbitrary patterns. We demonstrate that each VS neuron is
      tuned to sense a particular aspect of optic flow that is generated during self
      motion. Thus the VS neurons in the fly supply visual information for the control
      of head orientation, body posture, and flight steering. To reveal the functional
      organization of the receptive fields of the 10 VS neurons, we determined with a
      new method the distributions of local motion sensitivities and local preferred
      directions at 52 positions in the fly's visual field. Each neuron was identified
      by intracellular staining with Lucifer yellow and three-dimensional
      reconstructions from 10-micron serial sections. Thereby the receptive-field
      organization of each recorded neuron could be correlated with the location and
      extent of its dendritic arborization in the retinotopically organized neuropil of
      the lobula plate. The response fields of the VS neurons, i.e., the distributions
      of local preferred directions and local motion sensitivities, are not uniform but
      resemble rotatory optic flow fields that would be induced by the fly during
      rotations around various horizontal axes. Theoretical considerations and
      quantitative analyses of the data, which will be presented in a subsequent paper,
      show that VS neurons are highly specialized neural filters for optic flow
      processing and thus for the visual sensation of self-motions in the fly.

PMID- 9535958
TI  - Postsaccadic enhancement of initiation of smooth pursuit eye movements in
      monkeys.
AB  - Step-ramp target motion evokes a characteristic sequence of presaccadic smooth
      eye movement in the direction of the target ramp, catch-up targets to bring eye
      position close to the position of the moving target, and postsaccadic eye
      velocities that nearly match target velocity. I have analyzed this sequence of
      eye movements in monkeys to reveal a strong postsaccadic enhancement of pursuit
      eye velocity and to document the conditions that lead to that enhancement. Smooth
      eye velocity was measured in the last 10 ms before and the first 10 ms after the
      first saccade evoked by step-ramp target motion. Plots of eye velocity as a
      function of time after the onset of the target ramp revealed that eye velocity at
      a given time was much higher if measured after versus before the saccade.
      Postsaccadic enhancement of pursuit was recorded consistently when the target
      stepped 3 degrees eccentric on the horizontal axis and moved upward, downward, or
      away from the position of fixation. To determine whether postsaccadic enhancement
      of pursuit was invoked by smear of the visual scene during a saccade, I recorded
      the effect of simulated saccades on the presaccadic eye velocity for step-ramp
      target motion. The 3 degrees simulated saccade, which consisted of motion of a
      textured background at 150 degrees/s for 20 ms, failed to cause any enhancement
      of presaccadic eye velocity. By using a strategically selected set of oblique
      target steps with horizontal ramp target motion, I found clear enhancement for
      saccades in all directions, even those that were orthogonal to target motion.
      When the size of the target step was varied by up to 15 degrees along the
      horizontal meridian, postsaccadic eye velocity did not depend strongly either on
      the initial target position or on whether the target moved toward or away from
      the position of fixation. In contrast, earlier studies and data in this paper
      show that presaccadic eye velocity is much stronger when the target is close to
      the center of the visual field and when the target moves toward versus away from
      the position of fixation. I suggest that postsaccadic enhancement of pursuit
      reflects activation, by saccades, of a switch that regulates the strength of
      transmission through the visual-motor pathways for pursuit. Targets can cause
      strong visual motion signals but still evoke low presaccadic eye velocities if
      they are ineffective at activating the pursuit system.

PMID- 9535959
TI  - Depression of synaptic efficacy at intermolt in crayfish neuromuscular junctions
      by 20-hydroxyecdysone, a molting hormone.
AB  - This report demonstrates that ecdysteroids can reduce synaptic transmission at an
      intermolt stage of a crustacean tonic neuromuscular junction by acting at a
      presynaptic site. The steroid molting hormone, 20-hydroxyecdysone (20-HE),
      appears to act through a rapid, nongenomic mechanism that decreases the
      probability of synaptic vesicle release and reduces the number of release sites.
      Quantal analysis revealed that fewer vesicles were released for a given stimulus
      when 20-HE was present, and this in turn accounted for the reduced synaptic
      efficacy. Reduced synaptic efficacy produced smaller evoked postsynaptic currents
      and smaller excitatory postsynaptic potentials (EPSPs) across the muscle fiber
      membrane. The reduction in EPSPs was observed among muscle fibers that were
      innervated by high- or low-output terminals. The behavior of crustaceans/crayfish
      during the molt cycle, when 20-HE is high, may be explained by the reduction in
      synaptic transmission. Crustaceans become quiescent during the premolt periods as
      do insects. The effects of 20-HE can be reversed with the application of the
      crustacean neuromodulator serotonin, which enhances synaptic transmission.

PMID- 9535960
TI  - Orienting gaze shifts during muscimol inactivation of caudal fastigial nucleus in
      the cat. I. Gaze dysmetria.
AB  - The cerebellar control of orienting behavior toward visual targets was studied in
      the head-unrestrained cat by analyzing the deficits of saccadic gaze shifts after
      unilateral injection of muscimol in the caudal part of the fastigial nucleus
      (cFN). Gaze shifts are rendered strongly inaccurate by muscimol cFN inactivation.
      The characteristics of gaze dysmetria are specific to the direction of the
      movement with respect to the inactivated cFN. Gaze shifts directed toward the
      injected side are hypermetric. Irrespective of their starting position, all these
      ipsiversive gaze shifts overshoot the target by a constant horizontal error (or
      bias) to terminate at a "shifted goal" location. In particular, when gaze is
      directed initially at the future target's location, a response with an amplitude
      corresponding to the bias moves gaze away from the actual target. Additionally,
      when gaze is initially in between the target and this shifted goal location, the
      response again is directed toward the latter. This deficit of ipsiversive gaze
      shifts is characterized by a consistent increase in the y intercept of the
      relationship between horizontal gaze amplitude and horizontal retinal error.
      Slight increases in the slope sometimes are observed as well. Contraversive gaze
      shifts are markedly hypometric and, in contrast to ipsiversive responses, they do
      not converge onto a shifted goal but rather underestimate target eccentricity in
      a proportional way. This is reflected by a decrease in the slope of the
      relationship between horizontal gaze amplitude and horizontal retinal error,
      with, for some experiments, a moderate change in the y-intercept value. The same
      deficits are observed in a different setup, which permits the control of initial
      gaze position. Correction saccades rarely are observed when visual feedback is
      eliminated on initiation of the primary orienting response; instead, they occur
      frequently when the target remains visible. Like the primary contraversive
      saccades, they are hypometric and the ever-decreasing series of three to five
      correction saccades reduces the gaze fixation error but often does not completely
      eliminate it. We measured the position of gaze after the final correction saccade
      and found that fixation of a visible target is still shifted toward the
      inactivated cFN by 4.9 +/- 2.4 degrees. This fixation offset is correlated to,
      but on average 54% smaller than, the hypermetric bias of ipsiversive responses
      measured in the same experiments. In conclusion, the cFN contributes to the
      control of saccadic shifts of the visual axis toward a visual target. The
      hypometria of contraversive gaze shifts suggests a cFN role in adjusting a gain
      in the translation of retinal signals into gaze motor commands. On the basis of
      the convergence of ipsiversive gaze shifts onto a shifted goal, the straightness
      of gaze trajectory during these responses and the production of misdirected or
      inappropriately initiated responses toward this shifted goal, we propose that the
      cFN influences the processes that specify the goal of ipsiversive gaze shifts.

PMID- 9535961
TI  - Orienting gaze shifts during muscimol inactivation of caudal fastigial nucleus in
      the cat. II. Dynamics and eye-head coupling.
AB  - We have shown in the companion paper that muscimol injection in the caudal part
      of the fastigial nucleus (cFN) consistently leads to dysmetria of visually
      triggered gaze shifts that depends on movement direction. Based on the
      observations of a constant error and misdirected movements toward the inactivated
      side, we have proposed that the cFN contributes to the specification of the goal
      of the impending ipsiversive gaze shift. To test this hypothesis and also to
      better define the nature of the hypometria that affects contraversive gaze
      shifts, we report in this paper on various aspects of movement dynamics and of
      eye/head coordination patterns. Unilateral muscimol injection in cFN leads to a
      slight modification in the dynamics of both ipsiversive and contraversive gaze
      shifts (average velocity decrease = 55 degrees/s). This slowing in gaze
      displacements results from changes in both eye and head. In some experiments, a
      larger gaze velocity decrease is observed for ipsiversive gaze shifts as compared
      with contraversive ones, and this change is restricted to the deceleration phase.
      For two particular experiments testing the effect of visual feedback, we have
      observed a dramatic decrease in the velocity of ipsiversive gaze shifts after the
      animal had received visual information about its inaccurate gaze responses; but
      virtually no change in hypermetria was noted. These observations suggest that
      there is no obvious causal relationship between changes in dynamics and in
      accuracy of gaze shifts after muscimol injection in the cFN. Eye and head both
      contribute to the dysmetria of gaze. Indeed, muscimol injection leads to parallel
      changes in amplitude of both ocular and cephalic components. As a global result,
      the relative contribution of eye and head to the amplitude of ipsiversive gaze
      shifts remains statistically indistinguishable from that of control responses,
      and a small (1.6 degrees) increase in the head contribution to contraversive gaze
      shifts is found. The delay between eye and head movement onsets is increased by
      7.3 +/- 7.4 ms for contraversive and decreased by 8.3 +/- 10.1 ms for ipsiversive
      gaze shifts, corresponding respectively to an increased or decreased lead time of
      head movement initiation. The modest changes in gaze dynamics, the absence of a
      link between eventual dynamics changes and dysmetria, and a similar pattern of
      eye-head coordination to that of control responses, altogether are compatible
      with the hypothesis that the hypermetria of ipsiversive gaze shifts results from
      an impaired specification of the metrics of the impending gaze shift. Regarding
      contraversive gaze shifts, the weak changes in head contribution do not seem to
      reflect a pathological coordination between eye and head but would rather result
      from the tonic deviations of gaze and head toward the inactivated side. Hence,
      our data suggest that the hypometria of contraversive gaze shifts also might
      result largely from an alteration of processes that specify the goal rather than
      the on-going trajectory, of saccadic gaze shifts.

PMID- 9535962
TI  - Dynamics of excitatory transmitter release: analysis of synaptic responses in CA3
      hippocampal neurons after repetitive stimulation of afferent fibers.
AB  - The patch-clamp technique (whole cell configuration) was used to record
      excitatory postsynaptic currents (EPSCs) evoked by repetitive stimulation (4
      pulses at 50-ms intervals) of afferent fibers in the stratum lucidum-radiatum.
      Different synaptic behaviors (EPSC patterns) were classified in terms of
      facilitation or depression of the mean amplitude of the second, third, and fourth
      EPSC with respect to the previous one. A large variety of EPSC patterns was
      observed by stimulating different afferent fibers. Experiments with the
      mGluR2/mGluR3 agonist 2-(2,3-dicarboxycyclopropyl)glycine (DCG-IV) (1 microM), a
      compound that reduces release at mossy but not at associative commissural fibers
      and therefore allows to identify the origin of synaptic responses, showed that
      particular EPSC patterns could not be associated to the activation of a specific
      type of synaptic input. To investigate the role of the probability of release in
      the dynamics of synaptic activity, the extracellular calcium concentration was
      varied from 0.8 to 4 mM in several experiments. EPSC patterns dominated by
      depression, characteristics of high release probability conditions, could be
      observed in the majority of the cases in the presence of higher calcium
      concentrations. A quantitative model for dynamics of transmitter release has been
      developed. Experimental results were compared with data computed with the model
      taking into account the probability of release and the time course of
      reavailability. This work indicates that short-term changes of presynaptic
      conditions occurring during a train of action potentials can account for the high
      variability of EPSC responses. The model that is proposed also suggests a general
      method of experimental data analysis to investigate the possible presynaptic
      mechanisms underlying long-lasting changes in synaptic efficacy.

PMID- 9535963
TI  - Biophysical characterization and functional consequences of a slowly inactivating
      potassium current in neostriatal neurons.
AB  - Neostriatal spiny projection neurons can display a pronounced delay in their
      transition to action potential discharge that is mediated by a slowly developing
      ramp depolarization. The possible contribution of a slowly inactivating A-type K+
      current (IAs) to this delayed excitation was investigated by studying the
      biophysical and functional properties of IAs using whole cell voltage- and
      current-clamp recording from acutely isolated neostriatal neurons. Isolation of
      IAs from other voltage-gated, calcium-independent K+ currents was achieved
      through selective blockade of IAs with low concentrations (10 microM) of the
      benzazepine derivative, 6-chloro-7,8-dihydroxy-3-allyl- 1-phenyl-2,3,4,5-tetra
      hydro-1H-3-benzazepine (APB; SKF82958) and subsequent current subtraction.
      Examination of the voltage dependence of activation showed that IAs began to flow
      at approximately -60 mV in response to depolarization. The voltage dependence of
      inactivation revealed that approximately 50% of IAs channels were available at
      the normal resting potential (-80 mV) of these cells, but that only 20% of the
      channels were available at membrane potentials corresponding to spike threshold
      (about -40 mV). At these depolarized membrane potentials, the rate of activation
      was moderately rapid (tau approximately 60 ms), whereas the rate of inactivation
      was slow (tau approximately 1.5 s). The time course of removal of inactivation of
      IAs at -80 mV also was relatively slow (tau approximately 1.0 s). The
      subthreshold availability of IAs combined with its rapid activation and slow
      inactivation rates suggested that this current should be capable of dampening the
      onset of prolonged depolarizing responses, but over time its efficacy should
      diminish, slowly permitting the membrane to depolarize toward spike threshold.
      Voltage recording experiments confirmed this hypothesis by demonstrating that
      application of APB at a concentration (10 microM) that selectively blocks IAs
      substantially decreased the latency to discharge and increased the frequency of
      firing of neostriatal neurons. The properties of IAs suggest that it should play
      a critical role in placing the voltage limits on the recurring episodes of
      subthreshold depolarization which are characteristic of spiny neurons recorded in
      vivo. However, the voltage dependence and recovery kinetics of inactivation of
      IAs predict that its effectiveness will vary exponentially with the level and
      duration of hyperpolarization which precedes depolarizing episodes. Thus long
      periods of hyperpolarization should increase the availability of IAs and dampen
      succeeding depolarizations; whereas brief epochs of hyperpolarization should not
      sufficiently remove inactivation of IAs, thereby reducing its ability to limit
      subsequent depolarizing responses.

PMID- 9535964
TI  - Muscarinic agonist-induced burst firing in immature rat olfactory cortex neurons
      In vitro.
AB  - Age-related changes in pre-/postsynaptic muscarinic (mAChR) and metabotropic
      glutamate (mGluR) responsiveness were studied in slices of olfactory cortex from
      both immature [postnatal day 16-22 (P16-P22)] and adult (>/=P40) rats, using a
      conventional intracellular recording technique. In adult neurons, bath
      application of the mAChR agonist oxotremorine-M (OXO-M; 10 microM), or the
      selective mGluR agonist 1-aminocyclopentane-1S-3R-dicarboxylic acid (1S,3R-ACPD;
      10 microM) evoked sustained membrane depolarizations, increases in input
      resistance, intense repetitive firing, and the appearance of a slow poststimulus
      afterdepolarizing potential (sADP). Excitatory postsynaptic potentials (EPSPs)
      evoked by local electrical stimulation of association fiber terminals were also
      depressed. In contrast, in neurons from immature slices, the 10 microM OXO-M
      induced membrane depolarization was followed by the appearance of spontaneous
      rhythmic epileptiform activity, which was voltage independent and reversible on
      drug wash out. Epileptiform bursts were abolished or reduced by coapplication of
      tetrodotoxin (1 microM), atropine (1 microM), pirenzepine (100-200 nM), the N
      methyl-D-aspartate (NMDA) receptor antagonist -amino-5-phosphonovaleric acid (
      APV; 100 microM), the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3
      dione (CNQX; 5-20 microM), the anesthetic-sedative barbiturate pentobarbitone
      (100 microM), or by raising the extracellular Mg2+ concentration, whereas a clear
      facilitatory effect was exhibited by the selective gamma-aminobutyric acid-A
      (GABAA) receptor blocker (-)-bicuculline methiodide (10 microM). The
      epileptogenic effects induced by OXO-M were indistinguishable from those produced
      by 4-aminopyridine (4-AP; 100-200 microM), although these latter actions were
      unaffected by atropine. In slices from immature animals, electrical stimulation
      of layer III association fibers in the presence of 10 microM OXO-M was
      accompanied by a dramatic prolongation of evoked depolarizing postsynaptic
      potentials (PSPs), with the appearance of recurrent superimposed spike
      discharges. This effect was readily reversed on wash out of OXO-M. No comparable
      age-dependent differences were observed in the nature or time course of 1S,3R
      ACPD-evoked pre- (or post)synaptic responses, even in immature cells where
      muscarinic epileptiform activity had previously been demonstrated. We suggest
      that the overall susceptibility toward muscarinic-induced epileptiform discharge
      in immature olfactory cortical neurons may depend on the functional integrity of
      presynaptic inhibitory mAChRs; additional contributing mechanisms were also
      considered.

PMID- 9535965
TI  - Development of excitatory circuitry in the hippocampus.
AB  - Assessing the development of local circuitry in the hippocampus has relied
      primarily on anatomic studies. Here we take a physiological approach, to directly
      evaluate the means by which the mature state of connectivity between CA3 and CA1
      hippocampal pyramidal cells is established. Using a technique of comparing
      miniature excitatory postsynaptic currents (mEPSCs) to EPSCs in response to
      spontaneously occurring action potentials in CA3 cells, we found that from
      neonatal to adult ages, functional synapses are created and serve to increase the
      degree of connectivity between CA3-CA1 cell pairs. Neither the probability of
      release nor mean quantal size was found to change significantly with age.
      However, the variability of quantal events decreases substantially as synapses
      mature. Thus in the hippocampus the developmental strategy for enhancing
      excitatory synaptic transmission does not appear to involve an increase in the
      efficacy at individual synapses, but rather an increase in the connectivity
      between cell pairs.

PMID- 9535966
TI  - Off-centric rotation axes in natural head movements: implications for vestibular
      reafference and kinematic redundancy.
AB  - Until now, most studies concerning active head movements in three dimensions have
      used the classical rotation vector description. Although this description yields
      both the orientation of the head rotation axis and the amount of rotation, it is
      incomplete because it cannot specify the location of this rotation axis in space.
      The latter is of importance for a proper picture of the vestibular consequences
      of active head movements and has relevance for the problem of how the brain deals
      with the inherent kinematic redundancy of the multijoint head-neck system. With
      this in mind, we have extended the rotation vector description by applying the
      helical axes approach, which yields both the classical rotation vector as well as
      the location of the rotation axis in space. Subjects (n = 7), whose head
      movements were recorded optically, were instructed to shift gaze naturally to
      targets in 12 different directions at an eccentricity of 40 degrees. The results
      demonstrate that the axes for these head movements occupy consistently different
      spatial locations. For purely horizontal movements, the rotation axis is located
      near a point midway between the two ear canals. For gaze shifts in other
      directions, the rotation axes are located below the ear canals along two circles,
      one for movements with an upward component (up circle), the other (typically
      larger in size) for movements with a downward component (down circle). Purely
      vertical movement (up and down) axes were located on the lower pole of the up and
      down circles, respectively. It was found that both circles, the upper poles of
      which coincided, became larger in size as movement amplitude increased, which
      means that the axis location shifts to lower and more eccentric locations with
      respect to the skull for larger flexion and extension movements. Although this
      pattern could be recognized in most subjects, there were consistent intersubject
      differences in the absolute size of the circles, their increase with movement
      amplitude, and in the relative sizes of the up and down circles. Because multiple
      vertebrae are involved in head movements, there are theoretically many
      possibilities to execute a certain head movement. The differences in circle
      patterns among subjects indicate different strategies in resolving this kinematic
      redundancy problem, a fact that was not apparent from the classical rotation
      vector part of our description, which yielded a rather uniform picture. A simple
      model suggests that the downward shift of the location of the rotation axis
      requires a modulation in vestibulo-ocular reflex gain of </=10% to maintain
      fixation of a near target during vertical head movement. The involvement of the
      otolith system in this process remains to be determined.

PMID- 9535967
TI  - Auditory motion induces directionally dependent receptive field shifts in
      inferior colliculus neurons.
AB  - This research focused on the response of neurons in the inferior colliculus of
      the unanesthetized mustached bat, Pteronotus parnelli, to apparent auditory
      motion. We produced the apparent motion stimulus by broadcasting pure-tone bursts
      sequentially from an array of loudspeakers along horizontal, vertical, or oblique
      trajectories in the frontal hemifield. Motion direction had an effect on the
      response of 65% of the units sampled. In these cells, motion in opposite
      directions produced shifts in receptive field locations, differences in response
      magnitude, or a combination of the two effects. Receptive fields typically were
      shifted opposite the direction of motion (i.e., units showed a greater response
      to moving sounds entering the receptive field than exiting) and shifts were
      obtained to horizontal, vertical, and oblique motion orientations. Response
      latency also shifted as a function of motion direction, and stimulus locations
      eliciting greater spike counts also exhibited the shortest neural latency. Motion
      crossing the receptive field boundaries appeared to be both necessary and
      sufficient to produce receptive field shifts. Decreasing the silent interval
      between successive stimuli in the apparent motion sequence increased both the
      probability of obtaining a directional effect and the magnitude of receptive
      field shifts. We suggest that the observed directional effects might be explained
      by "spatial masking," where the response of auditory neurons after stimulation
      from particularly effective locations in space would be diminished. The shift in
      auditory receptive fields would be expected to shift the perceived location of a
      moving sound and may explain shifts in localization of moving sources observed in
      psychophysical studies. Shifts in perceived target location caused by auditory
      motion might be exploited by auditory predators such as Pteronotus in a
      predictive tracking strategy to capture moving insect prey.

PMID- 9535968
TI  - Dopamine modulates graded and spike-evoked synaptic inhibition independently at
      single synapses in pyloric network of lobster.
AB  - Bath application of dopamine (DA) modifies the rhythmic motor pattern generated
      by the pyloric network in the stomatogastric ganglion of the spiny lobster,
      Panulirus interruptus. Synaptic transmission between network members is an
      important target of DA action. All pyloric neurons employ both graded transmitter
      release and action-potential-mediated synaptic inhibition. DA was previously
      shown to alter the graded synaptic strength of every pyloric synapse. In this
      study, we compared DA's effects on action-potential-mediated and graded synaptic
      inhibition at output synapses of the lateral pyloric (LP) neuron. At each synapse
      the postsynaptic cell tested was isolated from other descending and pyloric
      synaptic inputs. DA caused a reduction in the size of the LP spike-evoked
      inhibitory postsynaptic potentials (IPSPs) in the pyloric dilator (PD) neuron.
      The change in IPSP size was significantly and linearly correlated with DA-induced
      reduction in the input resistance of the postsynaptic PD neuron. In contrast,
      graded inhibition, tested in the same preparations after superfusing the
      stomatogastric ganglion (STG) with tetrodotoxin (TTX), was consistently enhanced
      by DA. DA shifted the amplitude of spike-evoked IPSPs in the same direction as
      the alteration of the postsynaptic cell input resistance at two additional
      synapses tested: DA weakened the LP spike-mediated inhibition of the ventricular
      dilator (VD) and reduced the VD input resistance, while strengthening the LP -->
      pyloric constrictor (PY) synapse and increasing PY input resistance. As
      previously reported, graded inhibition was enhanced at these two LP output
      synapses. We conclude that DA can differentially modulate the spike-evoked and
      graded components of synapses between members of a central pattern generator
      network. At the synapses we studied, actions on the presynaptic cell predominate
      in the modulation of graded transmission, whereas effects on postsynaptic cells
      predominate in the regulation of spike-evoked IPSPs.

PMID- 9535969
TI  - Pharmacologically and functionally distinct calcium currents of stomatogastric
      neurons.
AB  - Previous studies have suggested the presence of different types of calcium
      channels in different regions of stomatogastric neurons. We sought to
      pharmacologically separate these calcium channel types. We used two different
      preparations from different regions of stomatogastric neurons to screen a range
      of selective calcium channel blockers. The two preparations were isolated cell
      bodies in culture, in which calcium current was measured directly, and isolated
      neuromuscular junction, in which synaptic transmission was the indirect assay for
      presynaptic calcium influx. The selective blockers were two different
      dihydropyridines, omega-Agatoxin IVA, and omega-Conotoxin GVIA. Cultured cell
      bodies possessed both high-threshold calcium current and calcium-activated
      outward current, similar to intact neurons. The calcium current had transient and
      maintained components, but both components had the same voltage dependence of
      activation and inactivation. Dihydropyridines at >/=10 microM blocked both high
      threshold calcium current and calcium-activated outward current. Nanomolar doses
      of omega-Agatoxin IVA did not block calcium current, but micromolar doses did.
      omega-Conotoxin GVIA did not block either current. In contrast, at the
      neuromuscular junction, dihydropyridines reduced the amplitude of postsynaptic
      potentials by only a modest amount, whereas omega-Agatoxin IVA at doses as low as
      64 nM reduced the amplitude of postsynaptic potentials almost entirely. These
      effects were presynaptic. omega-Conotoxin GVIA did not change the amplitude of
      postsynaptic potentials. The different pharmacological profiles of the two
      isolated preparations suggest that there are at least two different types of
      calcium channel in stomatogastric neurons and that omega-Agatoxin IVA and
      dihydropridines can be used to pharmacologically distinguish them.

PMID- 9535970
TI  - Reversible inactivation of monkey superior colliculus. I. Curvature of saccadic
      trajectory.
AB  - The neurons in the intermediate layers of the monkey superior colliculus (SC)
      that discharge before saccadic eye movements can be divided into at least two
      types, burst and buildup neurons, and the differences in their characteristics
      are compatible with different functional contributions of the two cell types. It
      has been suggested that a spread of activity across the population of the buildup
      neurons during saccade generation may contribute to the control of saccadic eye
      movements. The influence of any such spread should be on both the horizontal and
      vertical components of the saccade because the map of the movement fields on the
      SC is a two-dimensional one; it should affect the trajectory of saccade. The
      present experiments used muscimol injections to inactivate areas within the SC to
      determine the functional contribution of such a spread of activity on the
      trajectory of the saccades. The analysis concentrated on saccades made to areas
      of the visual field that should be affected primarily by alteration of buildup
      neuron activity. Muscimol injections produced saccades with altered trajectories;
      they became consistently curved after the injection, and successive saccades to
      the same targets had similar curvatures. The curved saccades showed changes in
      their direction and speed at the very beginning of the saccade, and for those
      saccades that reached the target, the direction of the saccade was altered near
      the end to compensate for the initially incorrect direction. Postinjection
      saccades had lower peak speeds, longer durations, and longer latencies for
      initiation. The changes in saccadic trajectories resulting from muscimol
      injections, along with the previous observations on changes in speed of saccades
      with such injections, indicate that the SC is involved in influencing the eye
      position during the saccade as well as at the end of the saccade. The changes in
      trajectory when injections were made more rostral in the SC than the most active
      burst neurons also are consistent with a contribution of the buildup neurons to
      the control of the eye trajectory. The results do not, however, support the
      hypothesis that the buildup neurons in the SC act as a spatial integrator.

PMID- 9535971
TI  - Reversible inactivation of monkey superior colliculus. II. Maps of saccadic
      deficits.
AB  - Neurons in the superior colliculus (SC) are organized as maps of visual and motor
      space. The companion paper showed that muscimol injections into intermediate
      layers of the SC alter the trajectory of the movement and confirmed previously
      reported effects on latency, amplitude, and speed of saccades. In this paper we
      analyze the pattern of these deficits across the visual field by systematically
      comparing the magnitude of each deficit throughout a grid of targets covering a
      large fraction of the visual field. We also translate these deficits onto the SC
      map of the visual/movement fields to obtain a qualitative estimate of the extent
      of the deficit in the SC. We found a consistent pattern of substantially
      increased saccadic latency to targets in the contralateral visual hemifield,
      accompanied by slight and inconsistent increases and decreases for saccades to
      the ipsilateral hemifield. The initial and peak speed of saccades was reduced
      after the injection. The postinjection amplitude of the saccades were either
      hypometric or normometric, but rarely hypermetric. Although errors in the initial
      direction of the postinjection saccades were small, they consistently formed a
      simple pattern: an initial direction with minimal errors (a null direction)
      separating regions with clockwise and counterclockwise rotations of the initial
      direction. However, the null direction did not go through the center of the
      inactivated zone, as would be expected if the SC alone were determining saccade
      direction, e.g., with a population code. One hypothesis that can explain the
      misalignment of the null direction with the lesion site is that another system,
      acting in parallel with the SC, contributes to the determination of saccadic
      trajectory.

PMID- 9535972
TI  - Electrophysiological and pharmacological characterization of the direct perforant
      path input to hippocampal area CA3.
AB  - Monosynaptic perforant path responses evoked by subicular stimulation were
      recorded from CA3 pyramidal cells of rat hippocampal slices. These monosynaptic
      responses were isolated by using low intensities of stimulation and by placing a
      cut through the mossy fibers. Perforant path-evoked responses consisted of both
      excitatory and inhibitory components. Excitatory postsynaptic currents (EPSCs)
      were mediated by both alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic
      acidreceptors (AMPAR) and N-methyl--aspartate receptors (NMDAR). Inhibitory
      postsynaptic currents consisted of gamma-aminobutyric acid-A (GABAA-) and -B
      (GABAB)-receptor-mediated components. At membrane potentials more positive than 
      60 mV and at physiological [Ca2+]/[Mg2+] ratios, >30% of perforant path evoked
      EPSC was mediated by NMDARs. This value varied as a function of the membrane
      voltage and external [Mg2+]. Two types of responses were observed after low
      intensity stimulation of the perforant path. The first type of response showed
      paired-pulse facilitation and was reduced by 2-amino-4-phosphonobutyric acid
      (AP4). The second type of response showed paired-pulse depression and was reduced
      by baclofen. Electrophysiological and pharmacological characteristics of these
      two types of responses are similar to the properties of lateral and medial
      perforant path-evoked EPSPs in the dentate gyrus.

PMID- 9535973
TI  - Plasticity of primary somatosensory cortex paralleling sensorimotor skill
      recovery from stroke in adult monkeys.
AB  - Adult owl and squirrel monkeys were trained to master a small-object retrieval
      sensorimotor skill. Behavioral observations along with positive changes in the
      cortical area 3b representations of specific skin surfaces implicated specific
      glabrous finger inputs as important contributors to skill acquisition. The area
      3b zones over which behaviorally important surfaces were represented were
      destroyed by microlesions, which resulted in a degradation of movements that had
      been developed in the earlier skill acquisition. Monkeys were then retrained at
      the same behavioral task. They could initially perform it reasonably well using
      the stereotyped movements that they had learned in prelesion training, although
      they acted as if key finger surfaces were insensate. However, monkeys soon
      initiated alternative strategies for small object retrieval that resulted in a
      performance drop. Over several- to many-week-long period, monkeys again used the
      fingers for object retrieval that had been used successfully before the lesion,
      and reacquired the sensorimotor skill. Detailed maps of the representations of
      the hands in SI somatosensory cortical fields 3b, 3a, and 1 were derived after
      postlesion functional recovery. Control maps were derived in the same hemispheres
      before lesions, and in opposite hemispheres. Among other findings, these studies
      revealed the following 1) there was a postlesion reemergence of the
      representation of the fingertips engaged in the behavior in novel locations in
      area 3b in two of five monkeys and a less substantial change in the
      representation of the hand in the intact parts of area 3b in three of five
      monkeys. 2) There was a striking emergence of a new representation of the
      cutaneous fingertips in area 3a in four of five monkeys, predominantly within
      zones that had formerly been excited only by proprioceptive inputs. This new
      cutaneous fingertip representation disproportionately represented behaviorally
      crucial fingertips. 3) There was an approximately two times enlargement of the
      representation of the fingers recorded in cortical area 1 in postlesion monkeys.
      The specific finger surfaces employed in small-object retrieval were
      differentially enlarged in representation. 4) Multiple-digit receptive fields
      were recorded at a majority of emergent, cutaneous area 3a sites in all monkeys
      and at a substantial number of area 1 sites in three of five postlesion monkeys.
      Such fields were uncommon in area 1 in control maps. 5) Single receptive fields
      and the component fields of multiple-digit fields in postlesion representations
      were within normal receptive field size ranges. 6) No significant changes were
      recorded in the SI hand representations in the opposite (untrained, intact)
      control hemisphere. These findings are consistent with "substitution" and
      "vicariation" (adaptive plasticity) models of recovery from brain damage and
      stroke.

PMID- 9535974
TI  - Handedness and asymmetry of hand representation in human motor cortex.
AB  - The cortical representation of five simple hand and finger movements in the human
      motor cortex was determined in left- and right-handed people with whole-head
      magnetoencephalography. Different movements were found to be represented by
      spatially segregated dipolar sources in primary motor cortex. The spatial
      arrangement of neuronal sources for digit and wrist movements was nonsomatotopic
      and varied greatly between subjects. As an estimator of hand area size in primary
      motor cortex, we determined the smallest cuboid volume enclosing the five dipole
      sources within the left and right hemisphere of each subject. Interhemispheric
      comparison revealed a significant increase of this volume in primary motor cortex
      opposite to the preferred hand. This asymmetry was due to a greater spatial
      segregation of neuronal dipole generators subserving different hand and finger
      actions in the dominant hemisphere. Mean Euclidean distances between dipole
      sources for different movements were 10.7 +/- 3.5 mm in the dominant and 9.4 +/-
      3.5 mm in the nondominant hemisphere (mean +/- SD; P = 0. 01, two-tailed t-test).
      The expansion of hand representation in primary motor cortex could not simply be
      attributed to a greater number of pyramidal cells devoted to each particular
      movement as inferred from current source amplitudes. The degree of hemispheric
      asymmetry of hand area size in the primary motor cortex was correlated highly
      with the asymmetry of hand performance in a standardized handedness test (r = 
      0.76, P < 0.01). These results demonstrate for the first time a biological
      correlate of handedness in human motor cortex. The expansion of hand motor cortex
      in the dominant hemisphere may provide extra space for the cortical encoding of a
      greater motor skill repertoire of the preferred hand.

PMID- 9535975
TI  - Kinematic coordination in human gait: relation to mechanical energy cost.
AB  - Twenty-four subjects walked at different, freely chosen speeds (V) ranging from
      0.4 to 2.6 m s-1, while the motion and the ground reaction forces were recorded
      in three-dimensional space. We considered the time course of the changes of the
      angles of elevation of the trunk, pelvis, thigh, shank, and foot in the sagittal
      plane. These angles specify the orientation of each segment with respect to the
      vertical and to the direction of forward progression. The changes of the trunk
      and pelvis angles are of limited amplitude and reflect the dynamics of both right
      and left lower limbs. The changes of the thigh, shank, and foot elevation are
      ample, and they are coupled tightly among each other. When these angles are
      plotted one versus the others, they describe regular loops constrained on a
      plane. The plane of angular covariation rotates, slightly but systematically,
      along the long axis of the gait loop with increasing V. The rotation, quantified
      by the change of the direction cosine of the normal to the plane with the thigh
      axis (u3t), is related to a progressive phase shift between the foot elevation
      and the shank elevation with increasing V. As a next step in the analysis, we
      computed the mass-specific mean absolute power (Pu) to obtain a global estimate
      of the rate at which mechanical work is performed during the gait cycle. When
      plotted on logarithmic coordinates, Pu increases linearly with V. The slope of
      this relationship varies considerably across subjects, spanning a threefold
      range. We found that, at any given V > 1 m s-1, the value of the plane
      orientation (u3t) is correlated with the corresponding value of the net
      mechanical power (Pu). On the average, the progressive rotation of the plane with
      increasing V is associated with a reduction of the increment of Pu that would
      occur if u3t remained constant at the value characteristic of low V. The specific
      orientation of the plane at any given speed is not the same in all subjects, but
      there is an orderly shift of the plane orientation that correlates with the net
      power expended by each subject. In general, smaller values of u3t tend to be
      associated with smaller values of Pu and vice versa. We conclude that the
      parametric tuning of the plane of angular covariation is a reliable predictor of
      the mechanical energy expenditure of each subject and could be used by the
      nervous system for limiting the overall energy expenditure.

PMID- 9535976
TI  - Temporal contrast enhancement via GABAC feedback at bipolar terminals in the
      tiger salamander retina.
AB  - Most retinal amacrine (ACs) and ganglion cells (GCs) express temporal contrast by
      generating action potentials at only the onset and offset of the light stimulus.
      This study investigated the neural mechanisms that underlie this temporal
      contrast enhancement. Whole cell patch recordings were made from bipolar cells
      (BCs), ACs, and GCs in the retinal slice preparation. The cells were identified
      by the locations of their somas in the inner nuclear layer and ganglion cell
      layers, their characteristic light responses, and morphology revealed by Lucifer
      yellow staining. Depolarizing a single BC with a brief voltage pulse elicited a
      Cl- tail current that was completely abolished when Ca2+ entry to bipolar
      terminals was prevented, by either removing Ca2+ from the Ringer solution or
      blocking Ca2+ channels with Co2+. This suggests that the Cl- current is Ca2+
      dependent. In those bipolar cells whose axon terminals were cutoff during slicing
      no Cl- current was observed, indicating that this current is generated at the
      synaptic terminals. The Cl- current consists of a predominant synaptic component
      that can be blocked by the non-N-methyl--aspartate (NMDA) glutamate receptor
      antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) or by the gamma
      aminobutyric acid-C (GABAC) receptor antagonist picrotoxin. There also exists a
      relatively small nonsynaptic component. Thus both glutamatergic and GABAergic
      transmission were involved in the generation of this Cl- current, suggesting that
      it is mediated by a recurrent feedback to bipolar cells. Picrotoxin, which blocks
      both GABAC receptors at BC terminals and GABAA receptors on the dendrites of ACs
      and GCs, converted the light-elicited voltage response in most - ACs and GCs from
      transient to sustained. Bicuculline, which blocks only the GABAA receptors, did
      not prolong the transient response in - ACs and GCs. This suggests that a
      negative feedback mediated by the GABAC receptor on the bipolar terminals is
      responsible for making these responses transient. After the GABAergic feedback
      was blocked with picrotoxin the light-elicited voltage responses (recorded under
      current clamp) were more sustained than the current responses (recorded under
      voltage clamp) to the same light stimuli. This suggests that a voltage-dependent
      conductance converts the relatively transient current responses to more sustained
      voltage responses. Our results imply a synaptically driven local GABAergic
      feedback at bipolar terminals, mediated by GABAC receptors. This feedback appears
      to be a significant component of the mechanism underlying temporal contrast
      enhancement in - ACs and GCs.

PMID- 9535978
TI  - Modulation of pre- and postsynaptic calcium dynamics by ionotropic glutamate
      receptors at a plastic synapse.
AB  - This study was conducted to assess the role of ionotropic glutamate receptors in
      the modulation of calcium dynamics on both sides of a vertebrate plastic synapse.
      Retrograde labeling of neuronal elements with high-affinity calcium-sensitive
      dyes was used in conjunction with confocal imaging techniques in an in vitro
      lamprey brain stem preparation. A prolonged calcium transient was measured both
      pre- and postsynaptically in response to a period of high-frequency ("tetanic")
      stimulation to the vestibulospinal-reticulospinal synapse. The ionotropic
      glutamate receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (10 microM)
      and D,L-2-amino-5-phosphonopentanoate (D,L-AP5; 100 microM) reduced the calcium
      signal in both compartments of the synapse. The presynaptic D,L-AP5-sensitive
      component was enhanced markedly by the removal of Mg2+ from the superfusate.
      Increasing the extracellular stimulus intensity progressively augmented the
      presynaptic calcium signal, suggesting the recruitment of excitatory axo-axonic
      inputs onto these fibers. Further, the presence of an excitatory amino acid
      mediated presynaptic potential underlying a component of the Ca2+ signal was
      demonstrated by electrophysiological recordings from vestibulospinal axons. Bath
      application of agonist, in the presence of tetrodotoxin (1 microM), confirmed the
      existence of N-methyl-D-aspartate receptors at the presynaptic element capable of
      modulating calcium levels. The postsynaptic Ca2+ response, which is known to be
      necessary for long-term potentiation (LTP) induction at this synapse, was
      localized to areas of the dendritic tree that correlated with the location of
      known synaptic inputs; thus the synaptically activated rise in postsynaptic
      calcium may confer the synapse specificity of LTP induction previously
      demonstrated. In summary, we have demonstrated the existence of physiologically
      activated presynaptic ionotropic glutamate receptors that are capable of
      modulating levels of intracellular calcium and have highlighted the importance of
      receptor-mediated increases in postsynaptic calcium for neuronal plasticity in
      the lamprey.

PMID- 9535977
TI  - L-Type calcium channels are required for one form of hippocampal mossy fiber LTP.
AB  - The requirement of postsynaptic calcium influx via L-type channels for the
      induction of long-term potentiation (LTP) of mossy fiber input to CA3 pyramidal
      neurons was tested for two different patterns of stimulation. Two types of LTP
      inducing stimuli were used based on the suggestion that one of them, brief high
      frequency stimulation (B-HFS), induces LTP postsynaptically, whereas the other
      pattern, long high-frequency stimulation (L-HFS), induces mossy fiber LTP
      presynaptically. To test whether or not calcium influx into CA3 pyramidal neurons
      is necessary for LTP induced by either pattern of stimulation, nimodipine, a L
      type calcium channel antagonist, was added during stimulation. In these
      experiments nimodipine blocked the induction of mossy fiber LTP when B-HFS was
      given [34 +/- 5% (mean +/- SE) increase in control versus 7 +/- 4% in nimodipine,
      P < 0.003]; in contrast, nimodipine did not block the induction of LTP with L-HFS
      (107 +/- 10% in control vs. 80 +/- 9% in nimodipine, P > 0.05). Administration of
      nimodipine after the induction of LTP had no effect on the expression of LTP. In
      addition, B- and L-HFS delivered directly to commissural/associational fibers in
      stratum radiatum failed to induce a N-methyl--aspartate-independent form of LTP,
      obviating the possibility that the presumed mossy fiber LTP resulted from
      potentiation of other synapses. Nimodipine had no effect on calcium transients
      recorded from mossy fiber presynaptic terminals evoked with the B-HFS paradigm
      but reduced postsynaptic calcium transients. Our results support the hypothesis
      that induction of mossy fiber LTP by B-HFS is mediated postsynaptically and
      requires entry of calcium through L-type channels into CA3 neurons.

PMID- 9535979
TI  - Effect of luminance contrast on BOLD fMRI response in human primary visual areas.
AB  - In this study, we examined the effect of stimulus luminance contrast on blood
      oxygenation-level-dependent (BOLD) functional magnetic resonance imaging within
      human visual cortex (V1 and extrastriate). Between experiments, the calibrated
      luminance of a single red LED covering 2 degrees of the subject's visual field
      was changed relative to a constant background luminance. This stimulus provided a
      different foveal luminance contrast for each experiment. We used an echo planar
      imaging sequence to collect blood-oxygenation-sensitive images during and in the
      absence of the presented stimulus. Our results showed that within V1 there was an
      increase in the spatial extent of activation with increasing stimulus contrast,
      but no trend was seen within extrastriate. In both V1 and extrastriate, the local
      mean activation level for all activated image pixels remained constant with
      increasing luminance contrast. However, when we investigated activated pixels
      common to all luminance contrast levels, we found that there was an increase in
      the mean activation level within V1, but not within extrastriate. These results
      suggest that there is an increase in the activity of cells in V1 with increasing
      luminance contrast.

PMID- 9535980
TI  - GABA-Induced intrinsic light-scattering changes associated with voltage-sensitive
      dye signals in embryonic brain stem slices: coupling of depolarization and cell
      shrinkage.
AB  - We have found new evidence for gamma-aminobutyric acid (GABA)-induced intrinsic
      optical changes associated with a voltage-sensitive dye signal in the early
      embryonic chick brain stem slice. The slices were prepared from 8-day-old
      embryos, and they were stained with a voltage-sensitive dye (NK2761). Pressure
      ejection of GABA to one site within the preparation elicited optical changes.
      With 580-nm incident light, two components were identified in the GABA-induced
      optical change. The first component was wavelength dependent, whereas the second,
      slower change was independent of wavelength. Comparison with the known action
      spectrum of the dye indicates that the first component reflects a depolarization
      of the membrane and that the second, slow component is a light-scattering change
      resulting from cell shrinkage coupled with the depolarization. Similar optical
      changes also were induced by glycine, although the amplitude of both the first
      and second signals was much smaller than for GABA. The optical changes induced by
      GABA persisted in the presence of picrotoxin and 2-hydroxysaclofen, suggesting
      that these optical responses include a novel GABA response, which has been termed
      GABAD in our previous reports.

PMID- 9535981
TI  - Attention-regulated activity in human primary visual cortex.
AB  - Effects of attention to a local contour of a moving object on the activation of
      human primary visual cortex (area V1) were examined. Local cerebral oxygenation
      changes (an index of neuronal activity) in human area V1 were measured with
      functional magnetic resonance imaging (fMRI) in conditions including the
      following two: 1) when attention was selectively directed toward one side of a
      moving wedge (the attention condition) and 2) when the wedges were viewed
      passively (the passive condition). Activation in area V1 was found to be higher
      in the attention condition than in the passive condition. To our knowledge, this
      is the first finding that attention to motion activates as early as area V1. We
      suggest that attentional activation of area V1 is task dependent.

PMID- 9535982
TI  - Spinal cord astrocytes display a switch from TTX-sensitive to TTX-resistant
      sodium currents after injury-induced gliosis in vitro.
AB  - Two distinct morphological subtypes of astrocytes have been shown to express Na+
      currents that differ biophysically and pharmacologically. Using an in vitro model
      for reactive gliosis, we recently reported marked changes in Na+ and K+ channel
      expression by astrocytes induced to proliferate. Using this in vitro assay in
      which a confluent monolayer of astrocytes is mechanically scarred to induce
      gliosis, we now demonstrate that sodium currents of scar-associated cells, in
      addition to doubling in current density, also switch from being tetrodotoxin
      sensitive(TTX-S, IC50 8 nM) to being approximately 40-fold more TTX-resistant
      (TTX-R,IC50 314 nM). These changes occurred within 6 h after injury and were not
      associated with any notable changes in cell morphology. Changes in biophysical
      properties were analyzed for the two current types. The activation curve for TTX
      R currents demonstrated a significant depolarized shift versus that of TTX-S
      currents (P </= 0. 003), and TTX-R currents have more depolarized V1/2 of
      activation (-33 vs. -23 mV). The V1/2 of inactivation was slightly, but not
      significantly, more depolarized for TTX-R currents as compared to TTX-S (-63 vs. 
      68 mV). Most notably, TTX-R currents showed significantly slower inactivation
      kinetics at depolarized voltage potentials than TTX-S sodium currents (0.76 vs.
      1.128 ms, at -10 mV; P < 0.0004).

PMID- 9535983
TI  - Neurons in the human thalamic somatosensory nucleus (Ventralis caudalis) respond
      to innocuous cool and mechanical stimuli.
AB  - A population of neurons in the principal somatosensory nucleus of human thalamus
      (ventralis caudalis, Vc) had a significant tonic, graded response to cool stimuli
      and also responded to innocuous mechanical stimuli (mechanical-cool neurons).
      These neurons were clustered at the dorsal aspect of medial Vc. Stimulation at
      the sites where these neurons were recorded evoked tingling sensations in the
      part of the body including or adjacent to the receptive field of these neurons.
      These neurons may contribute to the mechanism that mediates the perception of
      cold in man.

PMID- 9535984
TI  - Painful stimuli evoke potentials recorded over the human anterior cingulate
      gyrus.
AB  - Clinical studies of cingulotomy patients and imaging studies predict that the
      human cingulate gyrus might display pain-related activity. We now report
      potentials evoked by painful cutaneous stimulation with a CO2 laser (LEP) and
      recorded from subdural electrodes over the medial wall of the hemisphere. In
      response to facial laser stimulation on both sides, a negative (latency 211-242
      ms) and then a positive wave (325-352 ms) were recorded from the cortex of right
      medial wall and from the falcine dura overlying the left medial wall. Medial wall
      LEPs were similar to scalp LEPs and were largest over the anterior cingulate and
      superior frontal gyri just anterior to motor cortex contralateral to the side of
      stimulation. These results demonstrate that there is significant direct
      nociceptive input to the human anterior cingulate gyrus (Brodmann's area 24).

PMID- 9535986
TI  - Intracortical microstimulation of bilateral frontal eye field.
AB  - We trained two monkeys to perform a fixation task. Intracortical microstimulation
      (ICMS) was applied to the monkey frontal eye field (FEF) while monkeys were
      fixating on one of five fixation LEDs. The ICMS was applied in two different
      manners. Under the single stimulation condition, ICMS was delivered to either
      right or left FEF. Under the paired stimulation condition, bilateral FEF were
      successively stimulated with an interval of 30-250 ms. The single stimulation
      elicited contraversive saccades. As reported previously, these saccades were not
      much affected by initial eye positions, maintaining the same vector. In contrast,
      the paired stimulation elicited double-step saccades. The first of the paired
      stimulation elicited constant vector saccades, but the second of the paired
      stimulation evoked saccades whose vector varied greatly depending on the eye
      position at the start of individual saccades. The second saccades, starting from
      various initial positions, were directed to the endpoint of saccades that were
      elicited from the same FEF site under the single stimulation condition. Endpoints
      of second saccades varied little despite variations of intervals of the
      stimulation pairs, ranging from 60 to 150 ms. On the basis of these observations,
      we propose a novel view that the FEF is involved in directing saccades to an
      internally referenced visual target.

PMID- 9535985
TI  - Ionic currents and electromotility in inner ear hair cells from humans.
AB  - The upright posture and rich vocalizations of primates place demands on their
      senses of balance and hearing that differ from those of other animals. There is a
      wealth of behavioral, psychophysical, and CNS measures characterizing these
      senses in primates, but no prior recordings from their inner ear sensory receptor
      cells. We harvested human hair cells from patients undergoing surgical removal of
      life-threatening brain stem tumors and measured their ionic currents and
      electromotile responses. The hair cells were either isolated or left in situ in
      their sensory epithelium and investigated using the tight-seal, whole cell
      technique. We recorded from both type I and type II vestibular hair cells under
      voltage clamp and found four voltage-dependent currents, each of which has been
      reported in hair cells of other animals. Cochlear outer hair cells demonstrated
      electromotility in response to voltage steps like that seen in rodent animal
      models. Our results reveal many qualitative similarities to hair cells obtained
      from other animals and justify continued investigations to explore quantitative
      differences that may be associated with normal or pathological human sensation.

PMID- 9535987
TI  - RSR13, a synthetic modifier of hemoglobin-oxygen affinity, enhances the recovery
      of stunned myocardium in anesthetized dogs.
AB  - RSR13 (2-[4-[[(3, 5-dimethylanilino)carbonyl]methyl]phenoxyl]-2-methylpropr ionic
      acid) is a synthetic allosteric modifier of oxygen (O2)-hemoglobin affinity that
      increases O2 release to tissue by allosterically stabilizing deoxyhemoglobin. We
      tested the hypothesis that RSR13 enhances the functional recovery of stunned
      myocardium in barbiturate-anesthetized dogs instrumented for measurement of left
      ventricular (LV) and aortic blood pressure, LV +dP/dtmax and subendocardial
      segment shortening (%SS) in ischemic [left anterior descending (LAD) coronary
      artery] and normal (left circumflex coronary artery) zones. The partial pressure
      of oxygen and the Hill coefficient at 50% saturation (P50 and n50, respectively)
      were determined in arterial blood samples by multiple point tonometry and
      nonlinear regression analysis. Coronary collateral blood flow in the LAD zone was
      quantified with radioactive microspheres. Dogs received intravenous vehicle
      (0.45% saline) or one of two doses of RSR13 (100 or 150 mg.kg-1 bolus followed by
      a 0.50 or 0.75 mg.kg-1.min-1 infusion, respectively) in a random manner. All dogs
      were subjected to five 5-min periods of LAD occlusion separated by 5-min periods
      of reperfusion and followed by 180 min of final reperfusion during which
      hemodynamics, %SS, arterial blood gases, P50 and n50 were determined at selected
      intervals. RSR13 caused no hemodynamic effects and coronary collateral blood flow
      was equivalent among groups. RSR13 increased P50 (+40 +/- 4% for the high dose)
      and decreased n50 (-31 +/- 2% for the high dose). LAD occlusion caused regional
      dyskinesia during each 5-min occlusion. Enhanced recovery of %SS by 180 min after
      final reperfusion was observed in dogs treated with high-dose RSR13 (47 +/- 9% of
      base line) but not low-dose RSR13 (10 +/- 18% of base line) or vehicle alone (2
      +/- 16% of base line). The results suggest that high-dose RSR13 improves the
      recovery of stunned myocardium throughout reperfusion in open-chest dogs. These
      findings may be related to increases in O2 availability to ischemic myocardium
      resulting from RSR13-induced stabilization of the deoxy form of hemoglobin.

PMID- 9535988
TI  - Cardiovascular pharmacology of the A2A adenosine receptor antagonist, SCH 58261,
      in the rat.
AB  - We characterized the in vivo cardiovascular profile of SCH 58261, 7-(2
      phenylethyl)-5-amino-2-(2-furyl)-pyrazolo-[4,3-e]-1,2, 4-triazolo[1,5-c]
      pyrimidine, a selective A2A adenosine receptor antagonist, in conscious, freely
      moving rats by use of the telemetry system. In normotensive rats, SCH 58261, at
      10 mg/kg i.p., significantly (P < .05) inhibited hypotension and tachycardia
      induced by the A2A receptor agonist 2-hexynyl-5'-N-ethylcarboxamidoadenosine
      (0.01 mg/kg i.p.), but not the bradycardic effect caused by the A1 receptor
      agonist 2-chloro-N6-cyclopentyladenosine (0.03 mg/kg i.p.). SCH 58261, when
      administered alone, at 0.1 and 1 mg/kg i.p., did not induce significant
      hemodynamic changes, but at 10 mg/kg i.p., it slightly increased both systolic
      blood pressure (SBP) and diastolic blood pressure (DBP) (+19 +/- 3 and +16 +/- 2
      mm Hg, respectively; P < . 01) and heart rate (HR) (+85 +/- 5 beats/min; P <
      .01). These effects were inhibited by adrenergic blockade with propranolol (30
      mg/kg i.p.) and phentolamine (10 mg/kg i.p.): -5 +/- 3 mm Hg on DBP and -12 +/-
      11 beats/min on HR (P < .01). In spontaneously hypertensive rats, SCH 58261, at 3
      and 10 mg/kg i.p., increased weakly both SBP (+19 +/- 5 mm Hg and +25 +/- 4 mm
      Hg) and DBP (+14 +/- 4 mm Hg and +23 +/- 4 mm Hg) vs. vehicle (P < .01) and HR
      (+45 +/- 17 and +64 +/- 18 beats/min vs. vehicle, respectively; P < .01). The
      data indicate that SCH 58261 retains A2A selective receptor antagonist properties
      in vivo. Its effect on cardiovascular sympathetic outflow further suggests that
      endogenous adenosine exerts a tonic vascular regulation through A2A receptors.
      Therefore, SCH 58261 can be a useful pharmacological tool for clarifying A2A
      mediated cardiovascular actions of adenosine.

PMID- 9535989
TI  - Nitric oxide selectively inhibits intracellular Ca++ release elicited by inositol
      trisphosphate but not caffeine in rat vascular smooth muscle.
AB  - The present study was designed to investigate whether nitric oxide (NO) could
      interfere with intracellular Ca++ release through different pathways in vascular
      smooth muscle. Phasic contractions of rat aorta induced by phenylephrine or
      caffeine in Ca++-free solution were used as an indicator of intracellular Ca++
      release through the inositol 1,4,5-triphosphate receptor pathway and the
      ryanodine receptor pathway, respectively. In addition, cytoplasmic Ca++
      concentration ([Ca++]i) in vascular smooth muscle cells was determined by
      fluorescence measurement. Acetylcholine (ACh) inhibited the phenylephrine-evoked
      phasic contractions in Ca++-free solution in endothelium-intact but not -denuded
      aortic rings in a dose-dependent manner. However, ACh did not affect the action
      of caffeine. The inhibition by ACh was blocked completely by the NO synthase
      inhibitor Nomega-nitro-L-arginine, which could be reversed totally by L-arginine
      but not D-arginine. Methylene blue, a soluble guanylate cyclase inhibitor, also
      abolished the inhibition by ACh. Sodium nitroprusside, an NO donor, attenuated
      the phenylephrine- but not caffeine-induced phasic contractions in denuded aortic
      rings in Ca++-free solution. The effect of sodium nitroprusside was reversed
      substantially by methylene blue. Furthermore, sodium nitroprusside inhibited the
      elevation of [Ca++]i induced by phenylephrine in vascular smooth muscle cells
      isolated from rat aorta in the absence of extracellular Ca++, which could be
      abolished significantly by methylene blue. These results suggest that NO
      selectively inhibits intracellular Ca++ release stimulated by inositol 1,4,5
      triphosphate, but not caffeine in vascular smooth muscle.

PMID- 9535991
TI  - Agonist-induced desensitization and down-regulation of the human kappa opioid
      receptor expressed in Chinese hamster ovary cells.
AB  - In this study, we examined whether the human kappa opioid receptor stably
      expressed in Chinese hamster ovary cells underwent desensitization and down
      regulation after prolonged exposure to the agonist (-)U50,488H. Pretreatment with
      (-)U50,488H led to a reduction in the magnitude of increase in [35S]GTPgammaS
      binding by the subsequent application of (-)U50,488H. The extent of
      desensitization was related to duration of exposure and (-)U50,488H
      concentration. Pretreatment with (-)U50,488H also reduced the potency of (
      )U50,488H in inhibiting forskolin-stimulated adenylate cyclase. In membranes of (
      )U50,488H-pretreated cells, the affinity of (-)U50,488H was lower than that in
      the untreated control, and GTPgammaS had no effect on (-)U50,488H affinity,
      consistent with the notion of uncoupling of the receptor-G protein complex by (
      )U50, 488H treatment. Down-regulation of the kappa opioid receptor also occurred
      on exposure to (-)U50,488H. Higher (-)U50,488H concentrations and/or longer
      incubation periods were required for down-regulation than for desensitization.
      The degree of down-regulation depended on the agonist concentration and
      incubation time. (-)U50,488H-induced desensitization and down-regulation were
      blocked by naloxone. (+)U50,488H, an inactive stereoisomer, did not cause
      desensitization or down-regulation. These results indicate that both processes
      were receptor-mediated. After incubation with (-)U50,488H and removal of (
      )U50,488H, both (-)U50,488H-induced [35S]GTPgammaS binding and receptor number
      returned to the control level, which indicates that both processes were
      reversible. Thus, desensitization and down-regulation of the kappa opioid
      receptor occur after agonist exposure and represent two different adaptation
      mechanisms.

PMID- 9535990
TI  - Role of spinal glutamatergic transmission in the ascending limb of the
      micturition reflex pathway in the rat.
AB  - This study was undertaken to evaluate the role of glutamate receptors at spinal
      synapses on the ascending limb of the micturition reflex. In urethane
      anesthetized female rats, a tungsten electrode was inserted stereotaxically into
      the dorsal part of the rostral pons to record field potentials which were evoked
      by electrical stimulation of the pelvic nerve (PLN) (1-15 V, 0.05 ms pulse
      duration at 100-300 Hz, 5-30 ms train duration). The effects of glutamate
      receptor antagonists administered intrathecally (i.t.) on the PLN-evoked field
      potentials in the dorsal part of the rostral brainstem were examined. PLN
      stimulation evoked short latency (10-22 ms) negative field potentials (85 +/- 4
      microV) in a limited area of the dorsal part of the rostral pons (bregma -9.0 to 
      8.4, L 0.5 to 1. 5, H 4.2 to 5.4). The i.t. administration of LY215490 (0.1-30
      microg), a competitive alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid
      (AMPA) receptor antagonist, reduced the amplitude of the evoked potentials in a
      dose-dependent manner; 84 +/- 6%, 59 +/- 11% (P < .001), 31 +/- 10% (P < .001),
      17 +/- 9% (P < .001) of control after 0.1, 1, 10, 30 microg of LY215490,
      respectively. The i.t. administration of MK-801 (1-100 microg), a noncompetitive
      N-methyl-D-aspartate (NMDA) receptor antagonist, also reduced the amplitude of
      the evoked potentials in a dose-dependent manner; 93 +/- 21%, 76 +/- 14%, 52 +/-
      9% (P < .001), 39 +/- 9% (P < .001) of control after 1, 10, 30, 100 microg of MK
      801, respectively. Combined administration of LY215490 (0.1 microg) and MK-801 (1
      microg), in doses which individually did not elicit a significant effect,
      markedly reduced the amplitude of the evoked potentials (27 +/- 9% of control, P
      = . 0002). These results suggest that AMPA and NMDA glutamatergic synaptic
      mechanisms play a key role in the spinal processing of afferent input from the
      bladder and that these mechanisms function synergistically in the ascending limb
      of the spinobulbospinal micturition reflex pathway.

PMID- 9535992
TI  - Dose-related effects of N-demethyl-N-isopropyl-8, 9-anhydroerythromycin A 6,9
      hemiacetal on gastric emptying of solids in healthy human volunteers.
AB  - The purpose of our study was to evaluate the effects of a new nonantibiotic
      motilide derived from erythromycin, EM574, on gastric emptying and to evaluate
      its safety. Thirty healthy volunteers received one of five oral doses of EM574
      (5, 10, 20, 30 mg and placebo) in a randomized, double-blind, five-period, cross
      over design; each dosing period was separated by 1-wk washout. Gastric emptying
      was measured by 13C-octanoic acid breath test. A total of 10, 20, 30 mg of EM574
      significantly accelerated both lag phase and gastric half-emptying time (P <
      .001) compared to placebo. The 5-mg dose of EM574 also significantly shortened
      the gastric half-emptying time (P < .05). Mean gastric half-emptying times were
      173, 158, 147, 149 min with EM574 5, 10, 20, 30 mg, respectively (placebo, mean
      189 min). EM574 accelerated gastric emptying in a dose-related manner (P < .001
      for linear trend, P < .05 for quadratic trend). However, the 30-mg dose did not
      accelerate gastric emptying more than the 20-mg dose. EM574 was well tolerated; 7
      of 56 participants receiving the 20- or 30-mg dose developed nausea, and only 2
      of 28 receiving the 30-mg dose experienced vomiting. EM574 accelerates gastric
      emptying in a dose-dependent manner with minimal side effects after a single
      administration of up to 20 mg. EM574 shows promise for treatment of patients with
      impaired gastric emptying.

PMID- 9535993
TI  - Zolpidem physical dependence assessed across increasing doses under a once-daily
      dosing regimen in baboons.
AB  - The current study examined behavioral effects and possible development of
      physical dependence after once-daily doses of zolpidem (0, 1.0, 3.2, 10.0, 32.0
      mg/kg intragastrically [i.g.]) in three baboons. Each dose was administered for
      17 days and then the dose was increased; the 32.0 mg/kg dose was administered for
      27 days. Baboons had access to food pellets for 20 hr/day beginning 15 min after
      dosing. Each day, baboons were presented with a fine motor task. Observation
      sessions were conducted 1 hr after dosing on days 1, 10, 12 and 14 of each dose
      condition and after termination of drug dosing. On days 10 and 14 of each dose
      condition, vehicle and flumazenil (5 mg/kg i.m.) were administered, respectively.
      Zolpidem increased the number of pellets obtained by two of three baboons. Vomit
      and/or retch and grimace (signs believed to be indicative of abdominal
      discomfort) were observed in one or two baboons during all zolpidem dose
      conditions (1.0-32.0 mg/kg). Time to complete the fine motor task increased dose
      dependently in all three baboons, and incoordination was observed during the task
      in two baboons at 10.0 and 32.0 mg/kg. Analysis of blood plasma showed that
      measurable levels of zolpidem were present 24 hr after dosing in all drug
      conditions. The signs of flumazenil-precipitated withdrawal were summarized on a
      9-point scale. Scores ranged from 1 to 5 in the 1.0 mg/kg condition, from 2 to 5
      in the 3.2 and 10.0 mg/kg conditions and from 4 to 6 in the 32.0 mg/kg condition.
      Signs that were considered intermediate in severity were observed. Specifically,
      tremor, jerk and/or rigidly braced posture was observed in one baboon at 1.0
      mg/kg, two baboons at the next two doses and all three baboons at 32.0 mg/kg.
      Vomit and/or retch also occurred in two baboons at dose conditions above 1.0
      mg/kg. Discontinuation of zolpidem dosing after 78 to 79 days resulted in mild
      withdrawal signs (e.g., number of pellets obtained were lower and number of 1-min
      intervals increased in which eyes were closed, or in which lying down, head lower
      than torso posture and/or withdrawn posture were observed) on the first day in
      two baboons. The peak withdrawal scores were 4 or 5 on days 5 to 10; two baboons
      vomited and/or retched and all three baboons showed tremor, jerk and/or rigidly
      braced posture. Thus, zolpidem produced physical dependence under once-daily
      dosing conditions, and the severity of the withdrawal syndrome can be
      characterized as intermediate.

PMID- 9535994
TI  - In vivo maternal-fetal-amniotic fluid pharmacokinetics of zidovudine in the
      pigtailed macaque: comparison of steady-state and single-dose regimens.
AB  - The purpose of this study was to characterize the disposition of zidovudine in
      the maternal-fetal-amniotic fluid unit in vivo. Zidovudine was administered as a
      constant-rate infusion or a bolus dose to the dam, fetus and amniotic cavity
      (bolus dose only) of the near-term pigtailed macaque model. A fetal-maternal
      plasma steady-state concentration ratio of 0.76 +/- 0.06 suggested that the drug
      was transferred extensively to the fetal compartment. Similarly, the mean fetal
      maternal plasma area under the curve (AUC) ratio after administration of an i.v.
      bolus dose to the dam was 0.84 +/- 0. 09. Both ratios were significantly less
      than unity (P < .05), which indicates that fetal exposure to zidovudine was lower
      than maternal exposure. The placental transfer of zidovudine was passive, with a
      clearance of approximately 2.0 ml/min/kg, about 35% of the rate of the placental
      blood flow marker antipyrine. Zidovudine concentration in the amniotic fluid was
      higher than that in the fetal plasma because the drug is eliminated slowly from
      the amniotic cavity. The steady-state and i.v. bolus experimental designs
      resulted in close estimates of the extent of placental transfer of zidovudine
      (steady-state fetal-maternal plasma concentration ratio or fetal-maternal plasma
      AUC ratio), which indicates that the extent of transfer of zidovudine is
      independent of the mode of drug administration. We predict that when zidovudine
      is administered orally to pregnant women, the average fetal exposure to
      zidovudine will be approximately three fourths of the maternal exposure. This
      observation suggests that the dose administered to the pregnant woman need not be
      changed even if the fetus is the primary target of therapy.

PMID- 9535995
TI  - Is the reduced efficacy of morphine in diabetic rats caused by alterations of
      opiate receptors or of morphine pharmacokinetics?
AB  - Because it generally is admitted that neuropathic pain is resistant to opioid
      analgesia, we investigated the effect of morphine on hyperalgesia in streptozocin
      induced diabetes in rats. The antinociceptive effect of morphine (0.5-4 mg/kg
      i.v.) on mechanical (paw pressure test), thermal (tail immersion test) and
      chemical (formalin test) hyperalgesia was reduced. To clarify the mechanisms
      involved in the alteration of morphine analgesia, the binding characteristics of
      mu and delta receptor agonists and the pharmacokinetics of morphine and its
      glucuronide metabolites morphine 3-glucuronide and morphine 6-glucuronide were
      determined. KD and Bmax values for [3H][D-Ala2,(Me)Phe4, Gly(ol)5]enkephalin and
      [3H][D-Pen2,D-Pen5]enkephalin to cerebral mu and delta opiate receptors were not
      altered by diabetes. Likewise, the plasma maximal concentration of morphine and
      metabolites, as well as the area under the curve, did not differ between diabetic
      and normal rats. Only the total clearance and the apparent volume of distribution
      of morphine were increased in diabetic rats, which suggests that the diabetes
      induced glycosylation of proteins might increase the distribution of morphine in
      the aqueous compartment. These data indicate that the reduced analgesic effect of
      morphine caused by diabetes cannot be explained by a decrease in opiate-receptor
      affinity or density but rather by kinetic alteration of morphine (increase of
      total clearance and of volume of distribution in comparison with healthy
      animals).

PMID- 9535996
TI  - Intravenous and oral l-alpha-acetylmethadol: pharmacodynamics and
      pharmacokinetics in humans.
AB  - Levo-alpha-acetylmethadol (LAAM) is a long-acting opioid agonist approved for use
      as a maintenance treatment for opioid dependence. Previous clinical studies
      report that the onset of the effects of LAAM is slower after parenteral
      administration than oral administration; however, preclinical studies suggest
      otherwise. This study examined the pharmacodynamic and pharmacokinetic profile of
      LAAM when given orally and intravenously to humans. Opioid-experienced volunteers
      (n = 6), who were not physically dependent on opioids, received LAAM (20 and 40
      mg/70 kg i.v. and p.o.) and placebo under double-blind, double-dummy conditions
      during five weekly experimental sessions. Behavioral, physiological, subjective
      and pharmacokinetic measures were collected before and for 96 hr after drug
      administration. Intravenous LAAM produced significant subjective and
      physiological effects that appeared within 5 min, whereas the effects of oral
      LAAM appeared more slowly within 1 to 2 hr after drug administration.
      Pharmacokinetic data indicate that the immediate effects of intravenous LAAM are
      largely attributable to the parent drug rather than the active metabolites, nor
      LAAM and dinor-LAAM. LAAM produced prototypic opioid agonist effects (i.e.,
      miosis, subjective ratings of high, nodding) that were of equal magnitude across
      routes, dose-related and of long duration (up to 60 hr). These data are in
      contrast to previous clinical reports and indicate that LAAM produces effects of
      immediate onset when administered parenterally, which suggests that intravenous
      LAAM possesses greater abuse potential than previously believed.

PMID- 9535997
TI  - PST2238: a new antihypertensive compound that antagonizes the long-term pressor
      effect of ouabain.
AB  - The inhibition of the long-term pressor effect of ouabain may be useful for the
      therapy of essential hypertension. Here, for the first time, a selective
      inhibitor of the ouabain pressor effect is described. In vitro, 17beta-(3-furyl)
      5beta-androstane-3beta, 14beta, 17alpha-triol (PST 2238) displaced ouabain from
      its binding sites on purified sodium, potassium ATPase enzyme (Na-K ATPase) (IC50
      1.7 x 10(-6) M) without interacting with other receptors involved in blood
      pressure regulation or hormonal control. In cultured renal cells, incubation with
      ouabain (10(-10) to 10(-8) M) for 5 days stimulated the Na-K pump at Vmax,
      whereas PST 2238 showed the same effect at micromolar concentration. The ouabain
      dependent increase in the Na-K pump rate was abolished by PST 2238 at
      concentrations from 10(-14) to 10(-9) M. In rats made hypertensive by chronic
      infusion of 50 microg/kg/day of ouabain, PST 2238 given p.o at very low doses
      (0.1-1 microg/kg/day for 4 weeks) abolished the increase in blood pressure and
      renal Na-K ATPase activity caused by ouabain. PST 2238 did not affect either
      blood pressure or renal Na-K ATPase activity in normotensive rats. In conclusion,
      PST 2238 is a very potent compound that normalizes both blood pressure and
      alterations in the Na-K pump caused by ouabain. Thus it represents the prototype
      of a new class of antihypertensive drugs that could be effective in forms of
      hypertension sustained by the concomitant increase of endogenous ouabain levels
      and alterations in the Na-K pump.

PMID- 9535998
TI  - Novel somatostatin analogs for the treatment of acromegaly and cancer exhibit
      improved in vivo stability and distribution.
AB  - The biodistribution of several radiolabeled somatostatin (SRIF) analogs was
      determined in the rat. Newly developed analogs BIM-23190 and BIM-23197 attained
      higher plasma levels and much greater target tissue concentrations than the
      clinically used BIM-23014 analog. Highest tissue concentrations of BIM-23190 and
      BIM-23197 were found in adrenal, kidney, pituitary and pancreas, tissues that are
      known to be abundant in mRNA for the somatostatin subtype 2 receptor. BIM-23190
      and BIM-23197 associated radioactivity in these tissues was prolonged compared
      with that of BIM-23014, especially in the SRIF-receptor-rich pituitary. BIM-23190
      and BIM-23197 were more stable in vivo and much less subject to biliary excretion
      than BIM-23014. These properties account for the elevated plasma and target
      tissue concentrations of these new SRIF analogs. Based on higher plasma levels,
      greater distribution to target tissues and longer in vivo stability, BIM-23190
      and BIM-23197 may prove to be superior to BIM-23014 for the treatment of
      acromegaly and some types of cancer.

PMID- 9535999
TI  - Effect of protein kinase C activation on N-methyl-D-aspartate-evoked release of
      adenosine and [3H]Norepinephrine from rat cortical slices.
AB  - The role of protein kinase C (PKC) in the N-methyl-D-aspartate (NMDA)-evoked
      release of adenosine (ADO) and [3H]norepinephrine (NE) from slices of rat
      parietal cortex was studied. In the absence of Mg++, the PKC activator phorbol 12
      myristate 13-acetate (1 microM, PMA) did not release either ADO or [3H]NE, but it
      potentiated the release of ADO evoked by 20 microM NMDA and the release of -3H-NE
      evoked by 100 microM NMDA. These potentiating effects of PMA on the NMDA-evoked
      release of ADO and [3H]NE were reversed by the PKC inhibitor GF109,203X (1
      microM). GF109,203X by itself had no effect on the NMDA-evoked release of either
      ADO or [3H]NE. In the presence of Mg++, PMA did not permit the NMDA-evoked
      release of [3H]NE to occur. These results indicate that PKC does not play an
      essential role in the NMDA-evoked release of either ADO or NE. However,
      activation of PKC potentiates the release of ADO and NE evoked by submaximal
      concentrations of NMDA. Activation of PKC will have the effect of increasing the
      inhibitory threshold provided by released ADO when only a few NMDA receptors are
      activated and will promote and accelerate excitatory responses when most of the
      available NMDA receptors become activated.

PMID- 9536000
TI  - Thapsigargin-induced secretion is dependent on activation of a cholera toxin
      sensitive and phosphatidylinositol-3-kinase-regulated phospholipase D in a mast
      cell line.
AB  - Release of secretory granules by rat RBL-2H3 mast cells is mediated primarily
      through activation of protein kinase C (PKC) and elevation of cytosolic free
      calcium ([Ca++]I). Here, we show that secretion was also dependent on the
      activation of a cholera toxin-sensitive phospholipase (PL) D in cells stimulated
      with thapsigargin. Wortmannin, LY294002, butanol, propranolol and Ro31-7549
      inhibited responses to variety of secretagogues in a manner consistent with the
      notion that secretion was regulated by both PLD and PKC in a phosphatidylinositol
      3-kinase-dependent manner. The effects of these inhibitors, however, were
      especially pronounced in cells activated by thapsigargin. This stimulant induced
      minimal stimulation of PLC but measurable activation of PLD, as assessed by
      formation of phosphatidylethanol in the presence of ethanol. The activation of
      PLD was suppressed by inhibitors of phosphatidylinositol-3-kinase and was
      dependent on a rise in [Ca++]i because thapsigargin failed to activate PLD and
      secretion when elevation of [Ca++]i was blocked. Treatment of cells with cholera
      toxin resulted in selective and similar enhancements in the activation of PLD and
      secretion by thapsigargin, whereas stimulation of PLC and PLA2 was unaffected. A
      role for PKC was indicated by the blockade of secretory response to thapsigargin
      by the PKC inhibitor Ro31-7549 and by the ability of the PKC agonist phorbol-12
      myristate-13-acetate to reverse the inhibition of secretion by inhibitors of PLD.
      Such results suggested that thapsigargin, by causing substantial increases in
      [Ca++]I, induced secondary signals via PLD and PKC that synergized a calcium
      signal for secretion.

PMID- 9536001
TI  - Agonist and inverse agonist activity at the dopamine D3 receptor measured by
      guanosine 5'--gamma-thio-triphosphate--35S- binding.
AB  - In this study, the ligand-receptor-G protein interactions of the dopamine D3
      receptor expressed in Chinese hamster ovary cells were investigated using
      guanosine 5'-[gamma-thio]triphosphate-[35S] ([35S]GTPgammaS) and receptor binding
      experiments. Dopamine stimulated the [35S]GTPgammaS binding in a guanine
      nucleotide, magnesium and sodium-dependent manner. Dopamine and quinpirole
      produced maximal stimulation of the [35S]GTPgammaS binding whereas (+)-7-OH-DPAT
      and (-)-3-PPP were partial agonists. Interestingly, several compounds previously
      classified as D2 receptor antagonists behaved as inverse agonists at the D3
      receptor, i.e., they inhibited the basal [35S]GTPgammaS binding in a dose
      dependent fashion. Haloperidol, (+)-UH-232, (+)-AJ-76 and raclopride were full
      inverse agonists but clozapine was a partial inverse agonist. Pertussis toxin
      treatment abolished the D3 receptor-mediated agonist as well as inverse agonist
      responses, indicating the involvement of Gi/Go proteins in both processes.
      According to the ternary complex model, agonists should bind with higher affinity
      to the G protein coupled receptor (RG) and thereby shift the equilibrium from
      free receptor (R) toward RG, which produces a biological response. However, an
      inverse agonist should bind with higher affinity to R than to RG and thereby
      inhibit the basal activity of the cell. We found that the high affinity agonist
      binding site (RG) was abolished by pertussis toxin treatment of the cells.
      However, the inverse agonists bound with the same affinity to untreated and
      pertussis toxin treated D3 receptor membranes. Thus, we found no evidence for the
      hypothesis that inverse agonists would shift the equilibrium from RG toward R by
      binding with higher affinity to R than to RG.

PMID- 9536002
TI  - Oncostatin M down-regulates basal and induced cytochromes P450 in human
      hepatocytes.
AB  - The effects of oncostatin M on the expression of different cytochrome P450 (CYP)
      isozymes has been investigated in human hepatocytes. The dose-response and time
      course analyses of effects on CYP1A2 and CYP3A4 isozymes revealed that maximal
      inhibition was reached after 48 hr of exposure of human hepatocytes to 25
      units/ml oncostatin M. Reductions in CYP1A2 and CYP3A4 activity produced by
      oncostatin M correlated with decreases in protein content, de novo protein
      synthesis and specific mRNA levels, thus suggesting that oncostatin M could down
      regulate CYP expression at the transcriptional level. The inhibitory potency of
      oncostatin M on CYP expression was compared with that of other cytokines
      belonging to the interleukin-6 receptor family (interleukin-6, interleukin-11 and
      leukemia inhibitory factor), and interferon-gamma, which is recognized to inhibit
      human CYP expression, and granulocyte colony-stimulating factor, a cytokine that
      shares structural homology with the interleukin-6 family but has a different
      transduction signal. Maximal reductions in CYP1A2 activity were reached after 48
      hr of treatment with cytokines. At that time, oncostatin M showed the highest
      inhibitory effects on CYP1A2 activity (38% of control), followed by interferon
      (49% of control) and interleukin-6 (60% of control), whereas minor effects were
      produced by the other cytokines (74-80%). Comparable decreases were observed for
      CYP2A6, CYP2B6 and CYP3A4 activities. Enzymatic activity and de novo protein
      synthesis of 3-methylcholanthrene-induced CYP1A2 and dexamethasone-induced CYP3A4
      were also reduced to a much greater extent by oncostatin M than by other
      cytokines. The results show that oncostatin M is the most effective cytokine in
      down-regulating CYP isozymes in human hepatocytes, and its effects were evident
      even after removal of the cytokine from the culture medium.

PMID- 9536003
TI  - Differential atrial versus ventricular activities of class III potassium channel
      blockers.
AB  - The atrial versus ventricular activities of Class III agents with differing K+
      channel blocking profiles were assessed in vitro in ferret atrial and right
      ventricular papillary muscles. In concentration-effective refractory period (ERP)
      response studies at 2 Hz and 32 degreesC, the selective IKr blockers dofetilide,
      E-4031 and d-sotalol, as well as ibutilide, an IKr blocker also reported to
      enhance inward Na+ current, displayed markedly greater efficacies in increasing
      atrial ERP (+90-110%) versus ventricular ERP (+10-20%). RP58866, a blocker of IK1
      and IKr, and tedisamil, primarily a blocker of Ito and IKr, increased atrial ERP
      with approximately 10-fold greater potencies than ventricular ERP, but with
      similar efficacies for both tissues (+60-80% with RP58866; +150-160% with
      tedisamil). Azimilide, a blocker of IKr and IKs, and indapamide, a blocker of
      IKs, displayed essentially "balanced" activities, increasing atrial and
      ventricular ERP with equivalent potencies and efficacies (+40-60% increases for
      both tissues). Frequency-dependence profiles at 32 degrees C varied between
      atrial and ventricular tissues, and there was no general correspondence between
      atrial versus ventricular selectivity and frequency-dependence profiles. In the
      papillary muscle preparation, increasing temperature from 32 degrees C to 37
      degrees C altered both magnitude and frequency dependence of response to K+
      channel blockers. These findings support the potential to selectively modulate
      atrial versus ventricular refractoriness with the targeting of appropriate K+
      channel subtypes, and further demonstrate the differential frequency and
      temperature dependence of varying K+ channel subtype blockade. Ultimately, the
      identification and targeting of an appropriate K+ channel subtype or mix of
      subtypes may result in the achievement of optimal atrial-selective activity for
      the treatment of supraventricular arrhythmias.

PMID- 9536004
TI  - The pharmacology of mesocortical dopamine neurons: a dual-probe microdialysis
      study in the ventral tegmental area and prefrontal cortex of the rat brain.
AB  - Receptor-specific compounds were applied by retrograde microdialysis to the
      ventral tegmental area (VTA) of the rat brain. The effects of intrategmental
      infusions on extracellular dopamine in the ipsilateral prefrontal cortex (PFC)
      were recorded with a second microdialysis probe. Intrategmental infusion of
      tetradotoxin (1 microM), muscimol (20 microM) or baclofen (50 microM) decreased
      extracellular dopamine in the PFC. Infusion of N-methyl-D-aspartate (NMDA) (300
      microM; 1 mM, 15 min) or kainate (50 microM, 15 min) increased extracellular
      dopamine in the PFC. The effects of the excitatory amino acids were suppressed by
      co-infusion with (+/-)-3(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (300
      microM), with (+/-)-2-amin-5-phosphonopentanoic acid (500 microM), with
      dizocilpine maleate (500 microM) (partly) or with 6-cyano-7-nitroquinoxaline-2,3
      dione (500 microM) (partly). Intrategmental infusion of carbachol (50 microM)
      increased extracellular dopamine in the PFC. These results provide evidence for
      the localization of GABAA, GABAB, NMDA, non-NMDA and cholinergic receptors on
      mesocortical neurons in the VTA. Intrategmental infusion of AP-5, (+/-)-2-amino-5
      phosphonopentanoic acid (500 microM), of (+/-)-3(2-carboxypiperazin-4-yl)-propyl
      1-phosphonic acid (300 microM), of (+)-3-amino-1-hydroxy-2-pyrrolidone (1 mM) and
      of 6-cyano-7-nitroquinoxaline-2,3-dione (500 microM) decreased extracellular
      dopamine in the PFC. Infusion of mecamylamine, of atropine, and of 3-[[(3, 4)
      dichlorophenyl)methyl]propyl](diethoxymethyl) phosphonic acid into the VTA did
      not modify extracellular dopamine in the PFC. Infusion of bicuculline (50 microM)
      and that of (-)-sulpiride (50 microM) were followed by an increase in
      extracellular dopamine in the PFC. These data suggest that mesocortical dopamine
      neurons, at the level of the VTA, are tonicly excitated by glutamatergic neurons
      by acting on NMDA and non-NMDA receptors and are tonicly inhibited by GABA and
      dopamine by acting on GABAA and D2 receptors, respectively. No tonic stimulation
      by cholinergic neurons was detected. The effects on mesocortical neurons and
      earlier published data on mesolimbic and nigrostriatal dopamine neurons are
      compared and discussed.

PMID- 9536005
TI  - The effects of ethanol and acetaldehyde on the metabolism of prostaglandin E2 and
      leukotriene B4 in isolated rat hepatocytes.
AB  - The effects of ethanol and acetaldehyde on the metabolism of leukotriene B4
      (LTB4) and PGE2 were investigated in isolated cultures of rat hepatocytes. LTB4
      undergoes initial cytochrome P450-dependent omega-oxidation leading to the
      principal metabolites 20-hydroxy-LTB4, 20-carboxy-LTB4 and the omega/beta
      oxidation product 18-carboxy-LTB4. The addition of low concentrations of ethanol
      (25 mM) dramatically changes the relative amounts of these metabolite products by
      inhibiting the alcohol dehydrogenase-mediated oxidation of 20-hydroxy-LTB4.
      Addition of acetaldehyde to the incubation, up to 1 mM, had no significant effect
      on overall metabolism or distribution of metabolites. Above 1 mM acetaldehyde,
      beta-oxidation of LTB4 was inhibited. Thus the effect of ethanol on the
      metabolism of LTB4 appears to be due to ethanol itself and not to secondary
      effects from the metabolic transformation of ethanol to acetaldehyde in the
      cells. PGE2 is metabolized in isolated rat hepatocytes to produce chain-shortened
      products of beta-oxidation characterized as dinor-PGE1, dinor-PGE2, tetranor
      PGE1, tauro-dinor-PGE1 and tauro-dinor-PGE2. Low concentrations of ethanol (25
      mM) were found to increase the relative concentration of dinor-PGE1 in the
      metabolic distribution, with a corresponding decrease in concentration of
      tetranor-PGE1. The amount of dinor-PGE2 that was produced remained relatively
      unchanged in response to increasing concentrations of ethanol. Acetaldehyde
      concentrations from 0.1 mM to 1 mM did not affect metabolite distribution or the
      overall magnitude of PGE2 metabolism. Concentrations of acetaldehyde higher than
      1 mM decreased all beta-oxidation metabolites. Ethanol, at physiologically
      relevant concentrations, could alter eicosanoid metabolism in the liver by
      inhibiting LTB4 metabolism and altering that of PGE2.

PMID- 9536006
TI  - Na-dependent transport of S-(1,2-dichlorovinyl)-L-cysteine by renal brush-border
      membrane vesicles.
AB  - Cytotoxicity after exposure to the nephrotoxicant S-(1, 2-dichloro-vinyl)-L
      cysteine (DCVC) requires transport of this cysteine conjugate across the cell
      membrane. Although several basolateral transport pathways have been implicated in
      the uptake of this compound into renal proximal cells, the identity of the
      process or processes associated with transport across the luminal membrane is
      unclear. We used a preparation of luminal brush-border membrane vesicles to
      characterize the transport of [35S]DCVC in rabbit kidney. An inwardly directed Na
      gradient stimulated the initial rate of DCVC uptake by 16-fold compared to uptake
      measured in the absence of Na+. The Na-dependent component of DCVC uptake was
      stimulated by imposition of an inside-negative electrical potential difference
      and was blocked by the presence of 5 mM unlabeled DCVC in the extravesicular
      solution. Transport of DCVC was adequately described by Michaelis-Menten kinetics
      with an apparent Kt of 0.5 mM. DCVC uptake was blocked by the presence in the
      extravesicular solution of 10 mM concentrations of phenylalanine, leucine and
      cysteine, but not by glycine, proline, lysine, taurine, N-acetyl DCVC, p
      aminohippurate, lactate or succinate. Unlabeled DCVC inhibited uptake of
      [14C]phenylalanine by a mechanism that exerted a greater effect on the apparent
      Kt than on the Jmax of phenylalanine, implicating a possible competitive
      interaction between these compounds. The carrier-mediated permeability of DCVC
      (defined as the ratio of Jmax/Kt) in luminal brush border membranes was as large
      as or larger than that reported for a battery of other organic electrolytes,
      including several amino acids and organic anions. We conclude that luminal
      transport of DCVC in rabbit proximal cells is limited to a single Na-cotransport
      process that also handles phenylalanine.

PMID- 9536007
TI  - Characterization of I2 imidazoline and sigma binding sites in the rat and human
      stomach.
AB  - Radioligand binding experiments were carried out to identify and characterize
      nonadrenoceptor [3H]idazoxan binding sites and [3H](1, 2-di-(2-tolyl)guanidine)
      binding sites in the rat and human stomach. Furthermore, we examined two selected
      aspects of their potential functional significance. Binding of [3H]idazoxan (Kd =
      11.1 nM and 12.4 nM, respectively) and [3H]DTG (Kd = 932 nM and 242 nM,
      respectively) to cell membranes from rat and human stomach was rapid, reversible,
      specific and saturable. In rat stomach, binding of the radioligands was inhibited
      by imidazolines and by nonimidazoline sigma-site ligands, respectively, at
      different rank orders of affinity, which suggests the existence of I2-imidazoline
      binding sites as well as sigma2-sites. In two functional models, the direct
      effects of I2-site ligands and sigma2-site ligands on gastric smooth muscle and
      glands were investigated. (1) Cirazoline, clonidine and 4-chloro-2-(2-imidazolin
      2-ylamino)-isoindoline (BDF 6143) failed to contract the longitudinal muscle of
      the rat stomach fundus; BDF 6143 also failed to induce relaxation of this
      preparation when it was precontracted with 30 mM KCl. (2) Clonidine, idazoxan,
      BDF 6143, 1, 2-di-(2-tolyl)guanidine, agmatine and (R)-3-(3-hydroxyphenyl)-N
      propylpiperidine up to 100 microM did not induce acid secretion from rabbit
      isolated gastric glands. Our data provide evidence that the rat stomach is
      endowed with sigma2 sites and I2 binding sites in addition to the previously
      identified non-I1/non-I2 [3H]clonidine binding sites. Our experiments also offer
      basic evidence of the existence of I2 and sigma binding sites in the human
      stomach. Neither the I2 and [3H]clonidine binding sites nor the sigma sites in
      rat stomach are directly related to a postsynaptic effect on gastric smooth
      muscle or to acid release from isolated gastric glands.

PMID- 9536008
TI  - Role of glutamate receptors and voltage-dependent calcium and sodium channels in
      the extracellular glutamate/aspartate accumulation and subsequent neuronal injury
      induced by oxygen/glucose deprivation in cultured hippocampal neurons.
AB  - Ischemia is believed to induce neuronal damage by causing a sustained increase in
      the level of extracellular excitatory amino acids. In our study, we have examined
      the relationship between oxygen/glucose deprivation-induced changes in
      extracellular glutamate/aspartate level and subsequent neuronal injury by
      pharmacological manipulation of glutamate receptors and calcium and sodium
      channels. Cultured hippocampal neurons were exposed to combined deprivation of
      oxygen/glucose for 40 to 50 min. These cultures developed acute neuronal swelling
      and widespread neuronal degeneration over the next 20 hr. The extracellular
      levels of glutamate and aspartate at the end of the oxygen/glucose deprivation
      period were measured by high-performance liquid chromatography, and neuronal
      injury was assessed by lactate dehydrogenase efflux assay after subsequent
      aerobic incubation of the cells in normal medium for 20 hr. Both N-methyl-D
      aspartate and non- N-methyl-D-aspartate receptor antagonists attenuated the
      extracellular level of glutamate/aspartate and the neuronal injury. L-type, N
      type and P-type calcium channel blockers each significantly attenuated the
      neuronal injury, although the increase in the extracellular glutamate/aspartate
      was not significantly inhibited by any subtype-specific calcium channel blocker
      alone. A combination of calcium channel blockers of the three subtypes showed the
      most prominent neuroprotective effect and inhibited glutamate release. The sodium
      channel blocker tetrodotoxin also attenuated both glutamate efflux and neuronal
      injury. These observations suggest that the overactivation of glutamate
      receptors, calcium channels and sodium channels leads to excitotoxic neuronal
      injury through enhancing glutamate efflux into the extracellular space under the
      condition of oxygen/glucose deprivation.

PMID- 9536009
TI  - Age-related decline in beta adrenergic and adenosine A1 receptor function in the
      heart are attenuated by dietary restriction.
AB  - Previously published reports from this laboratory have shown that the
      antiadrenergic effect of adenosine A1 agonists declines with age in the rat heart
      [ J Mol Cell Cardiol 29:593-602] and that this decline may be caused by a
      decrease in coupling between adenosine A1 receptors (AdoA1R) and guanine
      nucleotide-binding proteins [ Circ Res 81:1065-1071]. Dietary restriction (DR;
      60% calories of ad libitum) has been shown to attenuate age-related changes in
      cellular signal transduction pathways. Therefore, the present study investigated
      whether DR altered the age-related changes in AdoA1R-mediated function in
      senescent rat hearts. Ventricular membranes were isolated from the hearts of ad
      libitum (AL) fed and DR male F344 rats that were 6, 12 and 24 months of age. In
      AL rats, there was an age-related decline in isoproterenol (ISO)-stimulated
      adenylyl cyclase when compared with the 6-month-old rats. The decline in ISO
      stimulated cyclase was attenuated in DR animals. In AL rats, inhibition of ISO
      stimulated adenylyl cyclase by the AdoA1R agonist, N6-p-sulfophenyladenosine
      (SPA) decreased with age. In DR rats, the age-related decline in inhibition was
      attenuated. Previous results from this laboratory indicated that in AL fed rats,
      there was an age-related decrease in the percentage of high-affinity binding
      sites for SPA, from 55% at 6 months to 23% at 24 months. Diet restriction
      attenuated this age-related shift in high-affinity binding sites so that the
      percentage of high-affinity sites at 24 months was 42%. Our results suggest that
      DR maintains AdoA1R function by preventing a loss of high-affinity AdoA1R sites.

PMID- 9536011
TI  - Glutamate receptor-mediated hyperexcitability after ethanol exposure in isolated
      neonatal rat spinal cord.
AB  - This study examined the mechanism for hyperexcitability after ethanol withdrawal
      from isolated neonatal rat spinal cord. Ethanol (65-130 mM, 30 min) significantly
      depressed the glutamate receptor-mediated population excitatory postsynaptic
      potential (pEPSP) underlying the monosynaptic reflex. On washing with drug-free
      solution the response recovered to levels significantly above control. Minimum
      ethanol exposure time required for induction of withdrawal hyperexcitability was
      approximately 15 min. A second application of ethanol after washout depressed the
      pEPSP to an extent similar to the first, and a second wash did not elevate
      response significantly more than the initial wash. Ethanol-induced
      hyperexcitability thus develops with a time course of minutes and plays a role in
      determining apparent initial ethanol potency. Both alpha-amino-3-hydroxy-5-methyl
      4-isoxazolepropionate and N-methyl-D-aspartate receptor-mediated components of
      the pEPSP were necessary for the expression of hyperexcitability on withdrawal
      but not for its induction. Butanol withdrawal also was associated with
      hyperexcitability, methanol was not. The case with octanol is uncertain because
      of slow recovery from this more lipophilic agent. Hyperexcitability on ethanol
      withdrawal was specific to the glutamate receptor-mediated pEPSP and not
      generalized to other evoked potentials. These results may be relevant to rapid
      and/or very rapid acute functional tolerance and to ethanol withdrawal.

PMID- 9536010
TI  - Diaminic carbonates, a new class of anti-inflammatory compounds: their biological
      characterization and mode of action.
AB  - Taking advantage of a standard assay on mouse LM cells (murine fibroblast-like
      cells), we found that several diaminic carbonates, a new class of organic
      compounds synthesized in our laboratories, were able to inhibit human tumor
      necrosis factor alpha (huTNFalpha)-induced cytotoxicity in a dose-dependent
      manner. Structure-function relationship studies indicated precise structural
      requirements for compounds being active as huTNFalpha inhibitors. ITF1779, one of
      the most active compounds in inhibiting huTNFalpha-induced cytotoxicity, was
      selected for further studies. In vitro experiments showed that ITF1779 inhibited
      not only huTNFalpha-induced cytotoxicity on LM cells but also another response of
      the same cells, interleukin-1-induced interleukin-6 production. Receptor-binding
      studies performed under nonequilibrium conditions and morphologic evidence of
      vacuole formation in cells treated with high concentrations of ITF1779 showed
      that the effects were strikingly similar to those of chloroquine, a
      lysosomotropic agent. Consistent with a mechanism of action of diaminic
      carbonates closely matching that of chloroquine are some structural similarities
      between the two classes of compounds, in particular their both being diprotic
      weak bases. Moreover, ITF1779 was shown to be active in vivo because it afforded
      protection against lipopolysaccharide-induced shock in mice, a systemic
      inflammatory response crucially dependent on tumor necrosis factoralpha
      production.

PMID- 9536012
TI  - Dopamine receptor antagonists in the nucleus accumbens attenuate analgesia
      induced by ventral tegmental area substance P or morphine and by nucleus
      accumbens amphetamine.
AB  - In the present study, we examined the effects of dopamine (DA) receptor
      antagonists infused into the nucleus accumbens septi (NAS) on analgesia induced
      by intra-ventral tegmental area (VTA) infusions of the substance P (SP) analog,
      DiMe-C7 or morphine and intra-NAS infusions of amphetamine. Rats received intra
      NAS infusions of either the mixed DA receptor antagonist flupenthixol (1.5 or 3.0
      microg/0.5 microl/side; DiMe-C7 only), the DA D1/D5 receptor antagonist SCH 23390
      (0.1 microg/0.5 microl/side; DiMe-C7 only) or the DA D2-type receptor antagonist
      raclopride (1.0, 3.0 or 5.0 microg/0.5 microl/side). Ten minutes later, rats
      received intra-VTA infusions of DiMe-C7 (3.0 microg/0.5 microl/side) or morphine
      (3.0 microg/0.5 microl/side) or intra-NAS infusions of amphetamine (2.5
      microg/0.5 microl/side). Animals were then administered the formalin test for
      tonic pain. Intra-NAS raclopride prevented analgesia induced by intra-VTA DiMe
      C7, intra-VTA morphine and intra-NAS amphetamine. Similarly, intra-NAS
      flupenthixol or SCH 23390 attenuated the analgesia induced by intra-VTA DiMe-C7.
      These findings suggest that tonic pain is inhibited, at least in part, by
      enhanced DA released from terminals of mesolimbic neurons. Furthermore, the
      evidence that SP and opioids in the VTA mediate stress-induced analgesia suggests
      that the pain-suppression system involving the activation of mesolimbic DA
      neurons is naturally triggered by exposure to stress, pain or both.

PMID- 9536014
TI  - Carrier-mediated transport of NG-nitro-L-arginine, a nitric oxide synthase
      inhibitor, in the pigmented rabbit conjunctiva.
AB  - In this study, the transport mechanism of NG-nitro-L-arginine (L-NA), a nitric
      oxide synthase inhibitor that may be useful for alleviating intraocular
      inflammation, was characterized in the pigmented rabbit conjunctiva. L-NA, when
      applied to the mucosal side of the conjunctiva, led to dose-dependent increases
      in the short-circuit current (Isc) at 37 degrees C but not at 4 degrees C or
      under the Na+-free condition. Serosally added 1 mM L-NA did not elicit any change
      in the Isc. Mucosally added 1 mM L-NA elicited a net absorptive Na+ flux of 0.09
      microEq/(cm2.hr), comparable with the Isc change. L-NA transport at 0.1 mM in the
      mucosal-to-serosal (ms) direction was 22 times greater than that in the serosal
      to-mucosal direction. There was a good correlation between the ms flux of L-NA
      and the Isc changes elicited by L-NA under the same experimental conditions. L-NA
      transport was saturable, with a Km of 0.35 mM and a maximal flux of 290
      pmol/(cm2.min). Hill analysis of L-NA flux observed at 0.1 mM L-NA in response to
      varying Na+ concentrations in the mucosal bathing fluid yielded a Hill
      coefficient of 0.98, suggesting a 1:1 coupling between Na+ and L-NA. Moreover, ms
      3H-L-NA transport was inhibited by basic amino acids (L-Arg and L-Lys) and a
      neutral amino acid (L-Leu), but not by an acidic amino acid (L-Glu) and the D
      stereoisomer of L-NA. In the case of L-Arg, inhibition was competitive with a Ki
      of 0.034 mM. Taken together, the above findings are consistent with the
      involvement of the L-Arg transport system B0,+ in the conjunctival transport of L
      NA.

PMID- 9536013
TI  - Cotransfection of second and third intracellular loop fragments inhibit
      angiotensin AT1a receptor activation of phospholipase C in HEK-293 cells.
AB  - Peptides from the intracellular regions of G protein-coupled receptors are useful
      probes of receptor-G protein coupling mechanisms. As a first step toward the
      genetic delivery of such "G protein inhibitors," we describe inhibition of
      angiotensin II (AII) receptor responses by expressed fragments of the second and
      third intracellular loops of the AT1a receptor (AT1a/i2 and AT1a/i3). Transient
      transfection of human embryonic kidney 293 cells with DNA encoding the rat AT1a
      receptor resulted in AII-dependent increases of inositol phosphates (maximum 4.5
      fold). Cotransfection of AT1a/i2 and AT1a/i3 fragments raised the EC50 for AII
      stimulation of phospholipase C activity 5-fold (from 0.18 nM to 0.99 nM, n = 12,
      P < .001) and 3-fold (from 0.38 nM to 1.2 nM, n = 8, P < .002), respectively. The
      combined effect of AT1a/i2 and AT1a/3 was additive, and transfection of an alpha
      1b adrenergic receptor third intracellular loop (alpha1b/i3) fragments also
      increased the EC50 for AII. Neither AT1a/i1 nor C-terminus (AT1a/Ct) constructs
      had significant effects on angiotensin responses. These data confirm a role for
      the second and third intracellular loops in angiotensin receptor responses and
      show the potential of this approach to blocking multiple phospholipase C-linked
      receptors.

PMID- 9536016
TI  - Cyanide-induced generation of oxidative species: involvement of nitric oxide
      synthase and cyclooxygenase-2.
AB  - In cerebellar granule cells, potassium cyanide (KCN) activates the NMDA receptor
      resulting in generation of nitric oxide and reactive oxygen species (ROS). To
      study the mechanism by which KCN stimulates ROS generation, the action of cyanide
      on the enzymatic pathways known to generate ROS were studied. The oxidant
      sensitive fluorescent dye, 2,7-dichlorofluorescin was used to measure
      intracellular levels of nitric oxide and ROS in cerebellar granule cells. Using
      selective enzyme inhibitors, it was shown that both protein kinase C and
      phospholipase A2 are involved in KCN-stimulated generation of NO and ROS. In
      cells treated with indomethacin or nordihydroguairetic acid, inhibitors of
      cyclooxygenase (COX) and lipoxygenase (LOX) respectively, attenuated
      (approximately 35%) KCN-induced generation of oxidant species. When L-NAME (LG
      nitro-L-arginine methyl ester) (nitric oxide synthase inhibitor, NOS) was
      combined with either indomethacin or nordihydroguairetic acid, generation of
      oxidant species was blocked by more than 80%. Pretreatment with NS398 (COX-2
      inhibitor) significantly decreased ROS generation indicating the involvement of
      COX-2 in KCN-induced oxidant generation. Treatment with L-NAME + NS398 blocked
      oxidant species generation, reflecting involvement of NOS. The participation of
      cytochrome P450 was not evident because SKF525A did not significantly reduce KCN
      induced ROS generation. Furthermore, a correlation was observed between oxidant
      generation and lipid peroxidation of cellular membranes (as determined by
      thiobarbituric acid levels). Pretreatment with inhibitors of protein kinase C,
      phospholipase A2 or COX, LOX, COX-2 partially blocked KCN-induced formation of
      thiobarbituric acid reactive substance, whereas coincubation of L-NAME with the
      inhibitors decreased lipid peroxidation by 60 to 90%. In cytotoxicity studies,
      KCN-induced cell death was partially blocked by the inhibitors and significant
      protection was observed when L-NAME was combined with these compounds. These
      findings show that activation of phospholipase A2 and subsequent metabolism of
      arachidonic acid by the COX-2 and LOX pathways and NOS contribute to cyanide
      induced ROS production.

PMID- 9536015
TI  - Binding of [3H]-SK&F 107260 and [3H]-SB 214857 to purified integrin
      alphaIIbbeta3: evidence for a common binding site for cyclic arginyl-glycinyl
      aspartic acid peptides and nonpeptides.
AB  - The aggregation of activated platelets is mediated by the binding of fibrinogen
      to its cell surface receptor, the integrin alphaIIbbeta3. The recognition of
      fibrinogen by alphaIIbbeta3 depends, in part, on the tripeptide sequence Arg-Gly
      Asp (RGD) in the adhesive protein. The interactions of a cyclic RGD-containing
      pentapeptide, [3H]-SK&F-107260, and a 1,4-benzodiazepine-based nonpeptide [3H]-SB
      214857, with purified alphaIIbbeta3 have been investigated. Both compounds
      potently inhibit platelet aggregation at submicromolar concentrations. Binding of
      both [3H]-SK&F-107260 (Kd = 1.19 nM) and [3H]-SB-214857 (Kd = 1.85 nM) to
      alphaIIbbeta3 is of high affinity and fully reversible. The binding is
      monophasic, indicating a single class of noncooperative binding sites. The two
      radioligands exhibited similar values in binding to alphaIIbbeta3 purified on an
      RGD-affinity column (Bmax = 0.2 mol/mol alphaIIbbeta3) or to alphaIIbbeta3
      purified over a lentil lectin column (Bmax = 0.03 mol/mol alphaIIbbeta3),
      suggesting that SK&F-107260 and SB-214857 interact with the same population of
      receptors. Binding of [3H]-SK&F-107260 and [3H]-SB-214857 to alphaIIbbeta3
      require divalent cations, Mg++, Ca++ and Mn++ are able to support binding, with
      Mn++ being the most effective. Thirteen alphaIIbbeta3 antagonists, including four
      linear and three cyclic RGD peptides, five peptidomimetics, the fibrinogen gamma
      chain dodecapeptide (HHLGGAKQAGDV) and the snake venom protein, echistatin,
      complete for [3H]-SK&F-107260 or [3H]-SB-214857 binding to alphaIIbbeta3. The
      affinity constants (Ki) of these compounds, determined by the two radioligand
      binding assays, are similar. Furthermore, these compounds exhibit the same rank
      order of potency in inhibiting biotinylated-fibrinogen binding to alphaIIbbeta3.
      Scatchard plot analyses of the [3H]-SK&F-107260 binding isotherms in the presence
      of unlabeled SB-214857 and gamma-chain dodecapeptide reveal competitive-type
      antagonism, indicating that SB-214857, gamma-chain dodecapeptide and SK&F-107260
      interact with mutually exclusive binding sites on alphaIIbbeta3.

PMID- 9536017
TI  - Chronopharmacology of granulocyte colony-stimulating factor in mice.
AB  - The role of the sensitivity of bone marrow cells to, and the pharmacokinetics of
      granulocyte colony-stimulating factor (G-CSF) on the rhythm of leukocyte
      increasing effect was investigated in ICR male mice housed under a standardized
      light-dark cycle (lights on at 0700, off at 1900). A significant circadian rhythm
      was demonstrated for leukocyte counts at 24 hr after G-CSF (250 microg/kg, s.c.)
      injection at six different circadian times (P < .01). The leukocyte counts of
      mice given G-CSF at 0500, 0900, 1300 or 1700 were significantly higher than those
      of mice given G-CSF at 2100 (P < .01, respectively). The rhythmic pattern
      resembled overall the rhythm occurring after saline injection. In the comparison
      between leukocyte counts after G-CSF injection at 0700 and 1900, the time when
      leukocyte counts are equal in nondrugged state, the leukocyte counts at 24 hr
      after G-CSF (250 microg/kg, i.v.) injection were approximately 50% higher in mice
      injected with the drug at 0700 than at 1900 (P < .01). Bone marrow cultures
      obtained at two times of day resulted in different numbers of myeloid colonies
      even when treated with the same concentrations of G-CSF in vitro. The colony
      forming activity of G-CSF was significantly more potent at 0700 than at 1900 (P <
      .01). The plasma G-CSF concentrations after G-CSF (250 or 5 microg/kg, i.v.)
      injection were significantly higher in mice receiving injections with the drug at
      0700 than at 1900 (P < .05, respectively). The area under the curve and mean
      residence time were significantly larger in mice injected with the drug at 0700
      than at 1900 (P < .01, P < .05, respectively). Our suggests that the rhythm of G
      CSF activity is caused by that of the sensitivity of bone marrow cells to, and
      the pharmacokinetics of the drug.

PMID- 9536018
TI  - Increases in acetylcholine release produced by phorbol esters are not mediated by
      protein kinase C at motor nerve endings.
AB  - Recent work from our laboratory has demonstrated that phorbol esters known to
      stimulate protein kinase C (PKC) also stimulate acetylcholine (ACh) secretion by
      an action at a strategic component of the secretory apparatus [ J Physiol (Lond)
      501:41-48]. In an attempt to determine whether the stimulatory effects of
      phorbols are mediated by PKC, we examined the effects of several PKC antagonists
      on ACh release promoted by phorbol 12,13-dibutyrate (PDBu) at the frog
      neuromuscular junction. PKC antagonists that act at the ATP binding site (C3
      domain) were examined for their ability to antagonize the stimulatory action of
      PDBu. Neither the nonselective PKC inhibitor, staurosporine (at concentrations as
      high as 1 microM), nor its more selective derivative, GF109203X (at
      concentrations as high as 10 microM), attenuated the stimulatory effects of PDBu.
      PKC antagonists that act at the phorbol ester binding site (C1 domain) were
      examined for their ability to antagonize the stimulatory action of PDBu. Neither
      sphingosine (500 microM) nor calphostin C (25 microM) reduced the stimulatory
      actions of PDBu on ACh release. These results suggest that a presynaptic protein
      possessing a phorbol ester receptor and not the enzyme PKC is the target site for
      the stimulatory effects of phorbol esters at motor nerve endings.

PMID- 9536019
TI  - Characterization of human neutrophil and endothelial cell ligand-operated
      extracellular acidification rate by microphysiometry: impact of reoxygenation.
AB  - Neutrophil (PMN) activation and recruitment are coordinated by ligand-operated
      surface receptors. These responses are involved in the tissue injury that follows
      hypoxia/reoxygenation. Here, we report that inflammatory mediators each evoke
      distinct and characteristic extracellular acidification rates (EAR) in both PMN
      and endothelial cells (EC) as measured by a Cytosensor microphysiometer.
      Leukotriene B4 (LTB4) and the peptide N-formylmethionyl-leucyl-phenylalanine were
      the most potent activators of EAR, whereas other potent stimuli including
      interleukin-8 and platelet-activating factor only weakly stimulated EAR in PMN.
      In contrast, other lipid-derived PMN mediators such as prostaglandin E2 and
      lipoxin A4 (LXA4) did not evoke EAR. Ligand-operated EAR exhibited
      desensitization as well as ligand specificity and sensitivity to pertussis toxin.
      Human endothelial cell agonists including histamine, prostacyclin stable analog
      and LXA4 each gave sharply different EAR responses, with only histamine evoking
      an EAR in these cells. Hypoxia/reoxygenation did not alter ligand-operated EAR
      from PMN, and similarly LTB4-stimulated PMN transendothelial migration, a
      functional response, was not influenced by either PMN or EC exposure to intervals
      of hypoxia/reoxygenation. LXA4 stable analogs inhibited PMN transendothelial
      migration (1 nM-1 microM), and this PMN-EC responsiveness to inhibition by a
      lipoxin stable analog (e.g., 16-phenoxy-LXA4) was enhanced approximately 2 log
      orders of magnitude after hypoxia/reoxygenation. Results demonstrate that ligand
      receptor interactions evoke characteristic profiles of EAR and that some well
      characterized ligand-receptor pairs (including interleukin-8, platelet-activating
      factor, prostaglandin E2 or LXA4) on these cell types either weakly activate the
      EAR pathway or are silent. Furthermore, hypoxia/reoxygenation did not alter LTB4
      PMN responses but did heighten responsiveness to 16-phenoxy-LXA4, which suggests
      a potential protective role in leukocyte-mediated injury.

PMID- 9536020
TI  - The effects of barium, dofetilide and 4-aminopyridine (4-AP) on ventricular
      repolarization in normal and hypertrophied rabbit heart.
AB  - The density of potassium channels, including the inward rectifying current (IK1),
      the delayed rectifying current and the transient outward current have been
      reported to be decreased in cardiac hypertrophy. However, it is not known whether
      the effects of specific ionic channel blockers are altered in this setting. The
      effects of barium chloride, which inhibits IK1, of dofetilide, which inhibits the
      rapidly activating component of the delayed rectifying current, and 4
      aminopyridine, which inhibits the transient outward current, were studied in
      isolated perfused working rabbit hearts. Cardiac hypertrophy was induced in
      rabbits by aortic banding. Hearts were removed 43 +/- 8 days after surgery, and
      electrophysiologic parameters were measured at low (30 cm H2O) and high (100 cm
      H2O) afterload at base line and during perfusion of barium, dofetilide or 4
      aminopyridine. The hearts from banded rabbits weighed more (13.0 +/- 2.3 g) than
      those from the sham controls (10.0 +/- 1.6 g; P < .001). The action potential
      duration at 90% repolarization (APD90) was greater in hypertrophied hearts (198
      +/- 16 msec) at base line than in control hearts (182 +/- 20 msec; P < .01).
      Barium (0.025 mM) caused greater prolongation of APD90 in hypertrophied hearts
      than in control hearts at both low afterload (214 +/- 9 msec vs. 195 +/- 20 msec)
      and high afterload (200 +/- 10 msec vs. 166 +/- 22 msec, P < .01). This
      interaction of barium's effects on APD90 and hypertrophy was highly statistically
      significant (P < .001). In contrast, dofetilide (15 nM) and 4-aminopyridine (1.0
      mM) caused similar changes in APD90 in hypertrophied hearts and in control hearts
      at low afterload and high afterload (P = NS). In isolated ventricular myocytes,
      IK1 and transient outward densities, but not the rapidly activating component of
      the delayed rectifying current were decreased in hypertrophied cells compared
      with control cells (P < .05). Thus the increased effects of barium on
      prolongation of APD in hypertrophy are probably due to the decreased density of
      IK1 in hypertrophy and perhaps, in part, to a change in the balance of
      repolarizing currents that occurs in hypertrophy.

PMID- 9536021
TI  - Effects of ketoconazole on triazolam pharmacokinetics, pharmacodynamics and
      benzodiazepine receptor binding in mice.
AB  - We previously demonstrated that ketoconazole is a potent inhibitor of triazolam
      biotransformation in vitro and in vivo. Despite significant elevations in
      triazolam plasma levels with coadministration of ketoconazole, the
      pharmacodynamic enhancement was lower than predicted based on plasma levels of
      triazolam. The present study examines the effects of ketoconazole on
      benzodiazepine receptor binding in vitro as well as on open-field behavior in
      male CD-1 mice. Triazolam alone inhibited [3H]flunitrazepam binding with an IC50
      value of 0.85 nM and a Ki value of 0.50 nM. Ketoconazole alone also competitively
      antagonized [3H]flunitrazepam binding in a concentration-dependent manner with an
      IC50 value of 1.56 microM and a Ki value of 1.17 microM. In the presence of 1, 3
      or 9 microM ketoconazole, the IC50 value of triazolam was increased to 1.11, 1.
      58 and 5.73 nM, respectively, whereas maximal binding was reduced by 36%, 69% and
      89%. Coadministration of 50 mg/kg ketoconazole and triazolam (0.1-0.3 mg/kg) to
      intact animals significantly elevated plasma and brain triazolam levels.
      Ketoconazole could be measured in mouse brain at levels averaging 31% of those in
      plasma. Ketoconazole alone had minimal or no effect on open field activity, but
      it significantly potentiated the decreased activity seen with triazolam
      administration. The ability of ketoconazole to inhibit triazolam displacement of
      [3H]flunitrazepam binding may explain the muted pharmacodynamic effect of this
      benzodiazepine in the presence of ketoconazole. Based on these results, it is
      likely that ketoconazole acts as a neutral ligand at the benzodiazepine receptor.

PMID- 9536022
TI  - Alterations in locomotor activity during chronic cocaine administration: effect
      on dopamine receptors and interaction with opioids.
AB  - Chronic cocaine administration can produce tolerance or sensitization to
      locomotor activating effects, depending on the treatment paradigm. The effects of
      chronic, continuous cocaine were measured on locomotor activity for 1 hr daily
      for 7 days. Cocaine produced significant increases in locomotor activity 4 hr
      after osmotic minipumps were implanted, and an even higher level of activity
      after 24 hr. This was likely a rapid sensitization to the locomotor activating
      effects of cocaine, because neither brain nor plasma levels of cocaine were
      significantly altered over the treatment period. By day 4, activity levels
      diminished, but remained significantly higher than in saline-treated animals.
      Twenty-four hr after pump removal, there were no changes in dopamine D1 or D2
      receptor binding, or in dopamine-stimulation of adenylyl cyclase activity in
      either caudate putamen or nucleus accumbens of cocaine-treated animals. Chronic
      naltrexone produced a slight, nonsignificant decrease in locomotor activity and
      when combined with cocaine, produced the same pattern of activity as cocaine
      alone, but with slightly less stimulation on all days. Morphine produced a
      smaller increase in activity than cocaine that remained constant throughout the
      treatment week. Cocaine with morphine was additive, producing greater activity
      and less tolerance than cocaine alone. Thus, continuous cocaine administration
      produces a rapid sensitization that is lost over the course of the treatment
      period, yet does not produce any immediate alterations in dopamine receptors or
      regulation of adenylyl cyclase. The pattern of behavior is not altered by an
      opioid antagonist, while the sensitization period appears to be prolonged in the
      presence of an opioid agonist.

PMID- 9536023
TI  - Comparative receptor binding analyses of cannabinoid agonists and antagonists.
AB  - To further characterize neuronal cannabinoid receptors, we compared the ability
      of known and novel cannabinoid analogs to compete for receptor sites labeled with
      either [3H]SR141716A or [3H]CP-55,940. These efforts were also directed toward
      extending the structure-activity relationships for cannabinoid agonists and
      antagonists. A series of alternatively halogenated analogs of SR141716A were
      synthesized and tested in rat brain membrane binding assays along with the
      classical cannabinoids, Delta9-tetrahydrocannabinol, cannabinol, cannabidiol, the
      nonclassical cannabinoid CP-55,940, the aminoalkylindole WIN55212-2 and the
      endogenous fatty acid ethanolamide, anandamide. Saturation binding isotherms were
      performed with both radioligands, as were displacement studies, allowing an
      accurate comparison to be made between the binding of these various compounds.
      Competition studies demonstrated that all of the compounds were able to displace
      the binding of [3H]CP-55,940 with rank order potencies that agreed with previous
      studies. However, the rank order potencies of these compounds in competition
      studies with [3H]SR141716A differed significantly from those determined with
      [3H]CP-55,940. These results suggest that CP-55,940, WIN55212-2 and other
      agonists interact with cannabinoid binding sites within the brain which are
      distinguishable from the population of binding sites for SR141716A, its analogs
      and cannabidiol. Structural modification of SR141716A significantly altered the
      affinity of the compound and its relative ability to displace either [3H]CP
      55,940 or [3H]SR141716A preferentially within the rat brain receptor membrane
      preparation.

PMID- 9536025
TI  - Effects of bis(2-chloroethyl)sulfide on ATP receptor-mediated responses of the
      rat vas deferens: possible relationship to cytotoxicity.
AB  - Extracellular ATP is a broad-spectrum cytotoxic agent that produces effects via
      cell surface P2 purinoceptors. The ligand-gated P2X purinoceptor subtype has very
      high sequence homology with the RP-2 gene, which encodes for apoptosis. The P2X
      RNA found in rat vas deferens is expressed preferentially by apoptotic
      thymocytes. P2X purinoceptor-mediated phasic (twitch) motor responses of the
      isolated rat vas deferens to neurogenic or exogenous ATP were rapidly,
      specifically and irreversibly potentiated by bis(2-chloroethyl)sulfide (HD 10-100
      microM). Both untreated and HD-potentiated neurogenic responses were Ca++
      dependent, blocked in the absence of Ca++ plus 0.1 mM EGTA, by the neuronal Ca++
      channel blocker omega-conotoxin-MVIIC (3 microM), by the P2 purinoceptor
      antagonist suramin (100 microM) and by tetrodotoxin (100 nM). HD also potentiated
      the effects of ATP on isolated guinea pig taenia caecum, where the nucleotide
      acts at G protein-coupled P2Y purinoceptor subtypes to cause relaxation. HD
      failed to inhibit the metabolism of ATP by ecto-ATPase in vas deferens or to
      cause the release of endogenous ATP. Potentiation of the twitch response to
      electric field stimulation by HD was attenuated or eliminated in tissues excised
      from rats previously challenged with topically applied HD, suggesting that HD
      absorbed into the systemic circulation had already effected maximal potentiation
      of ATP responses before in vitro testing. The physiological consequences of HD
      induced potentiation of the extracellular actions of ATP are discussed in
      relation to apoptosis and necrosis.

PMID- 9536024
TI  - Calcium-activated potassium channels and nitrate-induced vasodilation in human
      coronary arteries.
AB  - In some but not all arterial beds, smooth muscle cell calcium-activated K+
      channels (KCa channels) play a central role in the mediation of the vasodilator
      response to nitric oxide (NO) and other nitrates. We investigated the effect of
      nitrates on KCa channels in the relaxation of human coronary arteries by means of
      isometric contraction experiments in arterial rings. We also measured whole-cell
      currents in freshly isolated human coronary artery vascular smooth muscle cells
      via the patch-clamp technique. Sodium nitroprusside, diethylamine-nitric oxide
      complex sodium salt and isosorbide mononitratre completely relaxed rings
      preconstricted with 5 microM serotonin and produced dose-dependent relaxations of
      5 microM serotonin-preconstricted human rings. The relaxations were inhibited by
      2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-oxyl 3-oxide (10 microM),
      which neutralizes nitric oxide. The KCa channel blockers iberiotoxin (100 nM) and
      tetraethylammonium ions (1 mM) significantly inhibited SNP-induced relaxations of
      human coronary arteries. Moreover, in the patch-clamp experiments, SNP (1 microM)
      stimulated KCa currents and spontaneous transient outward K+ currents carried by
      Ca spark activated KCa channels. The SNP-induced (1 microM) KCa current was
      strongly inhibited by iberiotoxin (100 nM). These data show that activation of
      KCa channels in smooth muscle cells contributes to the vasodilating actions of
      nitrates and nitric oxide in human coronary arteries. This finding may have
      unique clinical significance for the development of antianginal and
      antihypertensive drugs that selectively target K+ channels and Ca sparks.

PMID- 9536026
TI  - Sodium valproate down-regulates the myristoylated alanine-rich C kinase substrate
      (MARCKS) in immortalized hippocampal cells: a property of protein kinase C
      mediated mood stabilizers.
AB  - Sodium valproate (VPA) is a short-chain fatty acid with well-established
      anticonvulsant properties and apparent clinical efficacy in the treatment of
      bipolar disorder (manic-depressive illness). Little is known regarding the
      mechanism of action of VPA in the brain that could account for this clinical
      therapeutic profile. Lithium has been the standard treatment for bipolar
      disorder, and it is known to be an uncompetitive inhibitor of inositol
      monophosphatase in the phosphoinositide (PI) signaling cascade at clinically
      relevant concentrations. Recent studies have provided data in support of a role
      for protein kinase C and the down-regulation of expression of the myristoylated
      alanine-rich C kinase substrate (MARCKS) in the long-term therapeutic action of
      lithium in the brain, which is dependent on both the relative activity of
      receptor-coupled PI signaling and the concentration of myo-inositol. Our current
      results demonstrated that valproate induces a concentration- and time-dependent
      reduction of MARCKS in immortalized hippocampal cells that appears to be
      independent of both the level of muscarinic receptor-activated PI signaling as
      well as the concentration of myo-inositol. In CHO-K1 cells transfected with the
      human m1 muscarinic receptor, unlike lithium, there is no evidence for receptor
      mediated accumulation of CMP-PA in the presence of VPA, providing more direct
      data for its lack of interaction within the PI signaling cascade. The action of
      VPA on MARCKS occurs within the therapeutic concentrations and time course
      observed in clinical studies of patients with bipolar disorder. Furthermore, the
      effect on MARCKS protein is additive in the presence of therapeutic
      concentrations of both lithium and valproate, consistent with clinical
      observations regarding the enhanced efficacy of the combination treatment.
      Finally, in studies examining acute and chronic effects of a variety of
      psychotropic compounds and VPA structural analogs, it is evident that the
      property of regulation of MARCKS is shared by the mood-stabilizers lithium and
      VPA, which may be specific to a class of drugs effective in the treatment of
      bipolar disorder.

PMID- 9536027
TI  - Tumor necrosis factor-alpha as a contributor in fumonisin B1 toxicity.
AB  - Fumonisin B1 is a toxic product of Fusarium moniliforme, which inhibits ceramide
      synthase, leading to accumulation of free sphingoid bases. Despite its known
      biochemical action, the mechanism of toxicity is not fully understood. Male
      BALB/c mice were injected subcutaneously with 0 to 6.75 mg/kg/day of fumonisin B1
      for 5 days. One day after the last treatment, spleens were collected, and
      peritoneal macrophages were obtained from separate groups after an
      intraperitoneal injection of thioglycolate broth. Peripheral leukocyte counts
      were increased and kidney weights were decreased by fumonisin B1 treatment.
      Presence of apoptotic cells in the liver and kidney of treated mice was confirmed
      by enzymatic immunoassay. Macrophages cultured with lipopolysaccharide indicated
      an increased secretion of tumor necrosis factor-alpha (TNF-alpha) but not of
      interleukin-1alpha. No effect was seen on interferon-gamma production when
      splenocytes were incubated with concanavalin A. Elevation of leukocyte and
      reticulocyte counts was abrogated by pretreatment with anti-TNF-alpha antibody
      before a single dose of fumonisin B1 (25 mg/kg), supporting the hypothesis that
      the fumonisin B1 toxicity involves TNF-alpha. Cultures of J774A.1 cells, when
      treated with fumonisin B1, produced TNF-alpha in vitro. Results indicate that
      fumonisin B1 toxicity may involve secretion of TNF-alpha by TNF-alpha-producing
      cells without altering interleukin-1alpha or interferon-gamma. The influence on
      TNF-alpha-production may be a contributing factor to fumonisin B1-induced
      apoptosis and other observed toxic effects in animals.

PMID- 9536028
TI  - Parallel contractile signal transduction pathways activated by receptors for
      thrombin and epidermal growth factor-urogastrone in guinea pig gastric smooth
      muscle: blockade by inhibitors of mitogen-activated protein kinase-kinase and
      phosphatidyl inositol 3'-kinase.
AB  - Using a guinea pig gastric longitudinal smooth muscle preparation, we have
      compared the contractile signaling pathways triggered by the thrombin receptor
      activating peptide, TFLLR-NH2 (TF) and by epidermal growth factor-urogastrone
      (EGF). In addition to inhibitors of tyrosine kinase [tyrphostin 47/AG213,
      genistein and the src-selective inhibitor CP118,556/PP1], cyclooxygenase
      (indomethacin, INDO) and diacylglycerol lipase (U57, 908), we also used the
      signal pathway probe inhibitors of mitogen-activated protein-kinase-kinase
      (MEK:PD98059), phosphatidylinositol 3'-kinase [PI3K: Wortmannin (WM) and
      LY294002], protein kinase C [PKC: GF109203X (GF)], and of the EGF-receptor kinase
      (PD153035). We found that in addition to the inhibition of both TF and EGF
      stimulated contractions by the inhibitors of tyrosine kinase, cyclooxygenase and
      diacylglycerol lipase, the actions of TF and EGF were also attenuated by PD98059,
      WM/LY294002 and GF. However, PD153035 blocked only EGF-triggered contractions.
      The contractile actions of both TF and EGF were dependent on extracellular
      calcium. In contrast, the contractile action of arachidonic acid, via a presumed
      cyclooxygenase product that mediated the contractions caused by both TF and EGF,
      was not blocked by any of the signal pathway probe inhibitors. The contractile
      actions of both TF and EGF were accompanied by increases in tissue phosphotyrosyl
      proteins and an increase in tissue c-src kinase activity. We conclude that
      protease-activated receptor no. 1- (thrombin receptor) mediated contractions in
      the logitudial muscle, like EGF receptor-activated responses, require the influx
      of extracellular calcium and use parallel signal pathways upstream of the
      cyclooxygenase step, involving MEK, PI3K, kinase C and possibly cellular src. The
      TF-induced response did not involve trans-activation of the EGF receptor kinase;
      but the converse (i.e., trans-activation of protease-activated receptor no. 1
      (thrombin receptor) by the EGF receptor kinase) could not be ruled out.

PMID- 9536029
TI  - Strain difference in sensitivity of mice to renal toxicity of inorganic mercury.
AB  - Inorganic mercury has a high affinity for the kidneys and causes acute renal
      failure. The present investigation was designed to determine the cause of the
      strain difference in sensitivity of mice to the renal toxicity of inorganic
      mercury. Renal damage caused by HgCl2 was estimated by histopathological and
      biochemical assessment, such as increase in blood urea nitrogen and plasma
      creatinine levels, and was found to be more remarkable in C3H/He than in C57BL/6
      mice. Increase in renal lipid peroxidation in C3H/He was greater than that in
      C57BL/6 mice. However, no strain difference was observed in renal activities of
      glutathione (GSH) peroxidase, superoxide dismutase and GSH S-transferase in HgCl2
      untreated mice. The GSH content and activities of catalase and GSSG reductase in
      kidney of HgCl2-untreated mice were higher in C3H/He than in C57BL/6. Background
      level of renal metallothionein content and the extent of metallothionein
      induction by HgCl2 showed no strain difference. On the other hand, renal mercury
      accumulation was higher and urinary mercury excretion was lower in C3H/He than in
      C57BL/6. The activity of renal gamma-glutamyltranspeptidase (gamma-GTP), which
      plays a key role in renal mercury accumulation, was higher in C3H/He than in
      C57BL/6. Furthermore, the increase in blood urea nitrogen by HgCl2, renal mercury
      accumulation and renal gamma-GTP activity in B6C3F1 mice were intermediate
      between those of the parent strains. These results suggest that the strain
      difference in renal toxicity of inorganic mercury seems to be caused by the
      discrepancy in renal mercury accumulation, and therefore, renal gamma-GTP may be
      an important factor determining the susceptibility of mice to the toxic action of
      inorganic mercury.

PMID- 9536030
TI  - Tyramine and vanadate synergistically stimulate glucose transport in rat
      adipocytes by amine oxidase-dependent generation of hydrogen peroxide.
AB  - Nonadrenergic imidazoline I2-binding sites colocalize with monoamine oxidase
      (MAO) in various tissues. As white adipocytes from various species have been
      reported to be very rich in I2-sites, the authors consider whether these cells
      show a substantial MAO activity and explore its functional role. Oxidation of
      [14C]tyramine by rat adipocyte membranes was dependent on both MAO and
      semicarbazide-sensitive amine oxidase (SSAO). Tyramine oxidation was identical in
      membranes and in intact adipocytes (Vmax: 11-12 nmol/min/mg protein). A similar
      effect of MAO and SSAO inhibitors was obtained in both the intact cells and the
      membranes: half of the activity was sensitive to semicarbazide and the other half
      more easily inhibited by MAO-A than by MAO-B inhibitors. As the reaction
      catalyzed by amine oxidases generates H2O2, which mimicks certain insulin effects
      in adipocytes, we tested whether tyramine oxidation influences glucose transport
      in adipocytes. One mM tyramine weakly stimulated glucose transport. A clear
      potentiation of tyramine effect occurred in the presence of 0.1 mM vanadate,
      ineffective by itself, reaching half-maximal insulin stimulation. This
      stimulation was sensitive to MAO and SSAO inhibitors and to catalase. The 5-fold
      activation of glucose transport was accompanied by translocation of GLUT4
      transporters to the plasma membrane. This shows that tyramine is readily oxidized
      by adipocytes and potentiates the effects of vanadium on glucose transport
      through release of hydrogen peroxide. The role of the amine oxidases, which are
      highly expressed in adipocytes, allows them to be considered as more than mere
      scavengers of circulating amines.

PMID- 9536031
TI  - Dopaminergic regulation of extracellular gamma-aminobutyric acid levels in the
      prefrontal cortex of the rat.
AB  - Dopaminergic axons in the prefrontal cortex synapse with interneurons as well as
      pyramidal cells. Electrophysiological data suggest that dopamine depolarizes
      certain gamma-aminobutyric acid (GABA)-containing interneurons in the cortex. We
      investigated the dopaminergic regulation of extracellular GABA levels in the
      prefrontal cortex using in vivo microdialysis. Systemic administration of the
      mixed D1/D2 dopamine receptor agonist apomorphine increased extracellular GABA
      levels in the prefrontal cortex, but did not increase levels of glycine; the
      apomorphine-elicited increase in GABA levels was blocked by tetrodotoxin infusion
      into the prefrontal cortex. Local administration of the D2 agonist quinpirole
      into the cortex via the dialysis probe resulted in a dose-dependent increase in
      extracellular GABA levels. In contrast, administration of the D1 agonist SKF
      38393 did not alter GABA levels. The ability of systemic apomorphine to increase
      extracellular GABA levels in the prefrontal cortex was blocked by local
      administration of the D2-like antagonist sulpiride to the cortex, but was not
      attenuated significantly by local perfusion of the D1 antagonist SCH 23390.
      Similarly, the ability of local infusion of the D2 agonist quinpirole to enhance
      extracellular GABA levels was blocked by sulpiride but not by SCH 23390. These
      data suggest that dopamine agonists increase the release of GABA in the
      prefrontal cortex through a D2-like receptor. In view of posited changes in
      prefrontal cortical dopamine and GABA systems in schizophrenia, it is possible
      that changes in GABAergic function in the cortex in schizophrenia are secondary
      to changes in cortical dopamine function.

PMID- 9536032
TI  - Pharmacological characterization of the human ionotropic glutamate receptor
      subtype GluR3 stably expressed in mammalian cells.
AB  - We have cloned the human ionotropic alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid (AMPA) receptor GluR3 flip splice variant (hGluR3i) and
      developed a stable cell line expressing this receptor in HEK293 cells.
      Electrophysiological recordings demonstrated that glutamate-evoked currents
      desensitize rapidly, with a mean desensitization time constant of 5.4 ms. Robust
      glutamate-evoked increases in intracellular Ca++ ([Ca++]i) were observed in the
      presence of cyclothiazide, which attenuated receptor desensitization. [Ca++]i
      measurements were used to perform a detailed pharmacological characterization of
      hGluR3i with reference agonists and antagonists. The results of these studies
      showed that kainate and domoate were not fully efficacious agonists relative to
      glutamate. The binding affinities of agonists and competitive antagonists were
      determined in a [3H]AMPA competition binding assay. There was a good correlation
      between the functional data and the binding affinities obtained for competitive
      antagonists. However, the binding affinities of the agonists did not correlate
      with their functional EC50 values from [Ca++]i data, possibly because the binding
      assay predominantly measures the desensitized high-affinity state of the
      receptor. [3H]AMPA binding also was performed on membranes prepared from rat
      forebrain, and comparison of the data from HEK293 cells expressing hGluR3i and
      rat forebrain suggest that nearly all of the reference compounds show similar
      binding activities between the two membrane preparations, with the exception of
      fluoro-willardiine, kainate and 6-nitro-7-sulfamoylbenzo(f)quinoxaline-2-3-dione
      (NBQX). These data suggest that cells stably expressing recombinant hGluR3i
      represent pharmacologically valid experimental systems to study human AMPA
      receptors.

PMID- 9536033
TI  - Quantitative autoradiography of halothane binding in rat brain.
AB  - 14C-halothane direct photoaffinity labeling was used to characterize the
      distribution of halothane binding in rat brain to test the hypothesis that
      anesthetics bind preferentially to a specific, heterogeneously distributed,
      receptor or channel. Slide-mounted sagittal rat brain sections were placed in gas
      tight quartz cuvettes with 100 microM 14C-halothane in phosphate buffered saline
      with 0 to 7.5 mM unlabeled halothane, or unlabeled chloroform and isoflurane at
      10 times the clinical EC50, and then exposed to UV light for 60 to 100 sec.
      Autoradiograms of nine brain regions (cortex, corpus callosum, hippocampal
      molecular and pyramidal layers, dentate molecular and granule cell layers, and
      cerebellar molecular, granular and white matter layers) were prepared and
      quantitated using Image 1.44. Total label incorporation was widespread, but
      exhibited subtle heterogeneity. There was significantly more total labeling in
      regions of high synaptic density than in regions containing primarily cell bodies
      or white matter. Most labeling (approximately 80%) was displaced by unlabeled
      halothane and can therefore be considered specific. Significantly more specific
      labeling was found in regions of high synaptic density. Isoflurane did not
      inhibit halothane photolabeling significantly, but chloroform inhibited it by
      approximately 50%. In conclusion, halothane photolabeling distribution in the
      mammalian brain is widespread, saturable and selective, but does not mimic the
      distribution of any individual receptor or channel. Brain regions with high
      synaptic density displayed the greatest degree of specific binding, consistent
      with transmission being an important functional target of volatile anesthetics.
      These results suggest a remarkably widespread individual target, or more likely,
      similar binding sites in multiple targets, and are consistent with the notion
      that anesthesia is the result of action at multiple sites.

PMID- 9536034
TI  - Differential agonist inhibition identifies multiple epibatidine binding sites in
      mouse brain.
AB  - The binding of [3H]epibatidine, an alkaloid isolated from the skin of an
      Ecuadorean tree frog, was measured both in brain regions dissected from mouse
      brain and in tissue sections. Binding to each of 12 brain areas was saturable,
      but apparently monophasic; no indication of multiple binding sites was obtained.
      However, inhibition of epibatidine binding by nicotine, acetylcholine,
      methylcarbachol and cytisine in olfactory bulbs revealed a biphasic pattern
      consistent with the presence of two sites differentially sensitive to inhibition
      by these nicotinic agonists. Cytisine displayed the greatest difference in
      inhibitory potency between the two apparent sites. Subsequent analysis of the
      inhibition of epibatidine binding by cytisine in membranes prepared from 12 brain
      areas also suggested the presence of two sites in each brain region. The
      estimated potency of cytisine at each site was similar in each brain region.
      However, the proportion of [3H]epibatidine binding sites that were more sensitive
      to inhibition by cytisine and those sites less sensitive to inhibition by this
      agonist varied markedly among the brain regions. Quantitative autoradiographic
      analyses of mouse brain revealed pattern of [3H]epibatidine binding sites less
      sensitive to inhibition by cytisine that differed markedly from the pattern
      obtained with [3H]nicotine. Among brain regions demonstrating substantial sites
      less sensitive to cytisine inhibition were the accessory olfactory nucleus,
      medial habenula, interpeduncular nucleus, fasciculus retroflexus, superior
      colliculus, inferior colliculus and the pineal gland. The results indicate that
      epibatidine binds to at least two distinct nicotinic sites in mouse brain that
      may represent different nicotinic receptor subtypes, one of which appears to be
      identical to that measured by the binding of other agonists such as nicotine or
      cytisine.

PMID- 9536035
TI  - The activated oxygen role of peroxisomes in senescence 

PMID- 9536036
TI  - Regulation of root and fungal morphogenesis in mycorrhizal symbioses 

PMID- 9536037
TI  - Nonphotochemical reduction of the plastoquinone pool in sunflower leaves
      originates from chlororespiration 
AB  - We investigated the relationship between nonphotochemical plastoquinone reduction
      and chlororespiration in leaves of growth-chamber-grown sunflower (Helianthus
      annuus L.). Following a short induction period, leaves of previously illuminated
      sunflower showed a substantially increased level of minimal fluorescence
      following a light-to-dark transition. This increase in minimal fluorescence was
      reversed by far-red illumination, inhibited by rotenone or photooxidative methyl
      viologen treatment, and stimulated by fumigation with CO. Using flash-induced
      electrochromic absorption-change measurements, we observed that the capacity of
      sunflower to reduce plastoquinone in the dark influenced the activation state of
      the chloroplast ATP synthase, although chlororespiratory transmembrane
      electrochemical potential formation alone does not fully explain our
      observations. We have added several important new observations to the work of
      others, forming, to our knowledge, the first strong experimental evidence that
      chlororespiratory, nonphotochemical plastoquinone reduction and plastoquinol
      oxidation occur in the chloroplasts of higher plants. We have introduced
      procedures for monitoring and manipulating chlorores-piratory activity in leaves
      that will be important in subsequent work aimed at defining the pathway and
      function of this dark electron flux in higher plant chloroplasts.

PMID- 9536038
TI  - Cyanogenesis in cassava. The role of hydroxynitrile lyase in root cyanide
      production 
AB  - In the cyanogenic crop cassava (Manihot esculenta, Crantz), the final step in
      cyanide production is the conversion of acetone cyanohydrin, the deglycosylation
      product of linamarin, to cyanide plus acetone. This process occurs spontaneously
      at pH greater than 5. 0 or enzymatically and is catalyzed by hydroxynitrile lyase
      (HNL). Recently, it has been demonstrated that acetone cyanohydrin is present in
      poorly processed cassava root food products. Since it has generally been assumed
      that HNL is present in all cassava tissues, we reinvestigated the enzymatic
      properties and tissue-specific distribution of HNL in cassava. We report the
      development of a rapid two-step purification protocol for cassava HNL, which
      yields an enzyme that is catalytically more efficient than previously reported
      (Hughes, J., Carvalho, F., and Hughes, M. [1994] Arch Biochem Biophys 311: 496
      502). Analyses of the distribution of HNL activity and protein indicate that the
      accumulation of acetone cyanohydrin in roots is due to the absence of HNL, not to
      inhibition of the enzyme. Furthermore, the absence of HNL in roots and stems is
      associated with very low steady-state HNL transcript levels. It is proposed that
      the lack of HNL in cassava roots accounts for the high acetone cyanohydrin levels
      in poorly processed cassava food products.

PMID- 9536039
TI  - Actin depolymerization affects stress-induced translational activity of potato
      tuber tissue 
AB  - Changes in polymerized actin during stress conditions were correlated with potato
      (Solanum tuberosum L.) tuber protein synthesis. Fluorescence microscopy and
      immunoblot analyses indicated that filamentous actin was nearly undetectable in
      mature, quiescent aerobic tubers. Mechanical wounding of postharvest tubers
      resulted in a localized increase of polymerized actin, and microfilament bundles
      were visible in cells of the wounded periderm within 12 h after wounding. During
      this same period translational activity increased 8-fold. By contrast, low-oxygen
      stress caused rapid reduction of polymerized actin coincident with acute
      inhibition of protein synthesis. Treatment of aerobic tubers with cytochalasin D,
      an agent that disrupts actin filaments, reduced wound-induced protein synthesis
      in vivo. This effect was not observed when colchicine, an agent that
      depolymerizes microtubules, was used. Neither of these drugs had a significant
      effect in vitro on run-off translation of isolated polysomes. However,
      cytochalasin D did reduce translational competence in vitro of a crude cellular
      fraction containing both polysomes and cytoskeletal elements. These results
      demonstrate the dependence of wound-induced protein synthesis on the integrity of
      microfilaments and suggest that the dynamics of the actin cytoskeleton may affect
      translational activity during stress conditions.

PMID- 9536040
TI  - Induced beta-carotene synthesis driven by triacylglycerol deposition in the
      unicellular alga dunaliella bardawil 
AB  - Under stress conditions such as high light intensity or nutrient starvation,
      cells of the unicellular alga Dunaliella bardawil overproduce beta-carotene,
      which is accumulated in the plastids in newly formed triacylglycerol droplets. We
      report here that the formation of these sequestering structures and beta-carotene
      are interdependent. When the synthesis of triacylglycerol is blocked, the
      overproduction of beta-carotene is also inhibited. During overproduction of beta
      carotene no up-regulation of phytoene synthase or phytoene desaturase is observed
      on the transcriptional or translational level, whereas at the same time acetyl
      CoA carboxylase, the key regulatory enzyme of acyl lipid biosynthesis, is
      increased, at least in its enzymatic activity. We conclude that under normal
      conditions the carotenogenic pathway is not maximally active and may be
      appreciably stimulated in the presence of sequestering structures, creating a
      plastid-localized sink for the end product of the carotenoid biosynthetic
      pathway.

PMID- 9536041
TI  - Expression and localization of phosphoenolpyruvate carboxylase in developing and
      germinating wheat grains.
AB  - Phosphoenolpyruvate carboxylase (PEPC) activity and corresponding mRNA levels
      were investigated in developing and germinating wheat (Triticum aestivum) grains.
      During grain development PEPC activity increased to reach a maximum 15 d
      postanthesis. Western-blot experiments detected two main PEPC polypeptides with
      apparent molecular masses of 108 and 103 kD. The most abundant 103-kD PEPC
      subunit remained almost constant throughout the process of grain development and
      in the scutellum and aleurone layer of germinating grains. The less-abundant 108
      kD polypeptide progressively disappeared during the second half of grain
      development and was newly synthesized in the scutellum and aleurone layer of
      germinating grains. PEPC mRNA was detected throughout the process of grain
      development; however, in germinating grains PEPC mRNA accumulated transiently in
      the scutellum and aleurone layer, showing a sharp maximum 24 h after imbibition.
      Immunolocalization studies revealed the presence of the enzyme in tissues with a
      high metabolic activity, as well as in the vascular tissue of the crease area of
      developing grains. A clear increase in PEPC was observed in the scutellar
      epithelium of grains 24 h after imbibition. The data suggest that the transiently
      formed PEPC mRNA in the scutellar epithelium encodes the 108-kD PEPC subunit.

PMID- 9536042
TI  - Evidence that the plant host synthesizes the heme moiety of leghemoglobin in root
      nodules 
AB  - Although it is well established that the plant host encodes and synthesizes the
      apoprotein for leghemoglobin in root nodules, the source of the heme moiety has
      been uncertain. We recently found that the transcript for coproporphyrinogen III
      oxidase, one of the later enzymes of heme synthesis, is highly elevated in
      soybean (Glycine max L.) nodules compared with roots. In this study we measured
      enzyme activity and carried out western-blot analysis and in situ hybridization
      of mRNA to investigate the levels during nodulation of the plant-specific
      coproporphyrinogen oxidase and four other enzymes of the pathway in both soybean
      and pea (Pisum sativum L.). We compared them with the activity found in leaves
      and uninfected roots. Our results demonstrate that all of these enzymes are
      elevated in the infected cells of nodules. Because these are the same cells that
      express apoleghemoglobin, the data strongly support a role for the plant in the
      synthesis of the heme moiety of leghemoglobin.

PMID- 9536044
TI  - Intracellular pH in arbuscular mycorrhizal fungi. A symbiotic physiological
      marker 
AB  - A method was developed to perform real-time analysis of cytosolic pH of
      arbuscular mycorrhizal fungi in culture using dye and ratiometric measurements
      (490/450 nm excitations). The study was mainly performed using photometric
      analysis, although some data were confirmed using image analysis. The use of
      nigericin allowed an in vivo calibration. Experimental parameters such as loading
      time and concentration of the dye were determined so that pH measurements could
      be made for a steady-state period on viable cells. A characteristic pH profile
      was observed along hyphae. For Gigaspora margarita, the pH of the tip (0-2
      &mgr;m) was typically 6.7, increased sharply to 7.0 behind this region (9.5
      &mgr;m), and decreased over the next 250 &mgr;m to a constant value of 6.6. A
      similar pattern was obtained for Glomus intraradices. The pH profile of G.
      margarita germ tubes was higher when cultured in the presence of carrot (Daucus
      carota) hairy roots (nonmycorrhizal). Similarly, extraradical hyphae of G.
      intraradices had a higher apical pH than the germ tubes. The use of a paper layer
      to prevent the mycorrhizal roots from being in direct contact with the medium
      selected hyphae with an even higher cytosolic pH. Results suggest that this
      method could be useful as a bioassay for studying signal perception and/or H+
      cotransport of nutrients by arbuscular mycorrhizal hyphae.

PMID- 9536043
TI  - The GA2 locus of Arabidopsis thaliana encodes ent-kaurene synthase of gibberellin
      biosynthesis.
AB  - The ga2 mutant of Arabidopsis thaliana is a gibberellin-deficient dwarf. Previous
      biochemical studies have suggested that the ga2 mutant is impaired in the
      conversion of copalyl diphosphate to ent-kaurene, which is catalyzed by ent
      kaurene synthase (KS). Overexpression of the previously isolated KS cDNA from
      pumpkin (Cucurbita maxima) (CmKS) in the ga2 mutant was able to complement the
      mutant phenotype. A genomic clone coding for KS, AtKS, was isolated from A.
      thaliana using CmKS cDNA as a heterologous probe. The corresponding A. thaliana
      cDNA was isolated and expressed in Escherichia coli as a fusion protein. The
      fusion protein showed enzymatic activity that converted [3H]copalyl diphosphate
      to [3H]ent-kaurene. The recombinant AtKS protein derived from the ga2-1 mutant is
      truncated by 14 kD at the C-terminal end and does not contain significant KS
      activity in vitro. Sequence analysis revealed that a C-2099 to T base
      substitution, which converts Gln-678 codon to a stop codon, is present in the
      AtKS cDNA from the ga2-1 mutant. Taken together, our results show that the GA2
      locus encodes KS.

PMID- 9536045
TI  - Biological activity of reducing-end-derivatized oligogalacturonides in tobacco
      tissue cultures.
AB  - The biological activity of reducing-end-modified oligogalacturonides was
      quantified in four tobacco (Nicotiana tabacum) tissue culture bioassays. The
      derivatives used were oligogalacturonides with the C-1 of their reducing end (a)
      covalently linked to a biotin hydrazide, (b) covalently linked to tyramine, (c)
      chemically reduced to a primary alcohol, or (d) enzymatically oxidized to a
      carboxylic acid. These derivatives were tested for their ability to (a) alter
      morphogenesis of N. tabacum cv Samsun thin cell-layer explants, (b) elicit
      extracellular alkalinization by suspension-cultured cv Samsun cells, (c) elicit
      extracellular alkalinization by suspension-cultured N. tabacum cv Xanthi cells,
      and (d) elicit H2O2 accumulation in the cv Xanthi cells. In all four bioassays,
      each of the derivatives had reduced biological activity compared with the
      corresponding underivatized oligogalacturonides, demonstrating that the reducing
      end is a key element for the recognition of oligogalacturonides in these systems.
      However, the degree of reduction in biological activity depends on the tissue
      culture system used and on the nature of the specific reducing-end modification.
      These results suggest that oligogalacturonides are perceived differently in each
      tissue culture system.

PMID- 9536046
TI  - The phytochrome response of the Lemna gibba NPR1 gene is mediated primarily
      through changes in abscisic acid levels.
AB  - Two important signaling systems involved in the growth and development of plants,
      those triggered by the photoreceptor phytochrome and the hormone abscisic acid
      (ABA), are involved in the regulation of expression of the NPR1 gene of Lemna
      gibba. We previously demonstrated that phytochrome action mediates changes in ABA
      levels in L. gibba, correlating with changes in gene expression evoked by
      stimulation of the phytochrome system. We have now further characterized
      phytochrome- and ABA-mediated regulation of L. gibba NPR1 gene expression using a
      transient particle bombardment assay, demonstrating that regulatory elements
      controlling responses to both stimuli reside within 156 nucleotides upstream of
      the transcription start. Linker scan (LS) analysis of the region from -156 to -70
      was used to identify two specific requisite and nonredundant cis-acting promoter
      elements between -143 to -135 (LS2) and -113 to -101 (LS5). Mutation of either of
      these elements resulted in a coordinate loss of regulation by phytochrome and
      ABA. This suggests that, unlike the L. gibba Lhcb2*1 promoter, in which
      phytochrome and ABA regulatory elements are separable, the phytochrome response
      of the L. gibba NPR1 gene can be attributed to alterations in ABA levels.

PMID- 9536047
TI  - Effect of ATP sulfurylase overexpression in bright yellow 2 tobacco cells.
      Regulation Of atp sulfurylase and SO4(2-) transport activities.
AB  - To determine if the ATP sulfurylase reaction is a regulatory step for the SO4(2-)
      assimilation pathway in plants, an Arabidopsis thaliana ATP sulfurylase cDNA,
      APS2, was fused to the 35S promoter of the cauliflower mosaic virus and
      introduced by Agrobacterium tumefaciens-mediated transformation into isolated
      Bright Yellow 2 tobacco (Nicotiana tabacum) cells. The ATP sulfurylase activity
      in transgenic cells was 8-fold that in control cells, and was correlated with the
      expression of a specific polypeptide revealed by western analysis using an anti
      ATP sulfurylase antibody. The molecular mass of this polypeptide agreed with that
      for the overexpressed mature protein. ATP sulfurylase overexpression had no
      effect on [35S]SO4(2-) influx or ATP sulfurylase activity regulation by S
      availability, except that ATP sulfurylase activity variations in response to S
      starvation in transgenic cells were 8 times higher than in the wild type. There
      were also no differences in cell growth or sensitivity to SeO4(2-) (a toxic SO4(2
      ) analog) between transgenic and wild-type cells. We propose that in Bright
      Yellow 2 tobacco cells, the ATP sulfurylase derepression by S deficiency may
      involve a posttranscriptional mechanism, and that the ATP sulfurylase abundance
      is not limiting for cell metabolism.

PMID- 9536049
TI  - Evidence for the critical role of sucrose synthase for anoxic tolerance of maize
      roots using a double mutant 
AB  - The induction of the sucrose synthase (SuSy) gene (SuSy) by low O2, low
      temperature, and limiting carbohydrate supply suggested a role in carbohydrate
      metabolism under stress conditions. The isolation of a maize (Zea mays L.) line
      mutant for the two known SuSy genes but functionally normal showed that SuSy
      activity might not be required for aerobic growth and allowed the possibility of
      investigating its importance during anaerobic stress. As assessed by root
      elongation after return to air, hypoxic pretreatment improved anoxic tolerance,
      in correlation with the number of SuSy genes and the level of SuSy expression.
      Furthermore, root death in double-mutant seedlings during anoxic incubation could
      be attributed to the impaired utilization of sucrose (Suc). Collectively, these
      data provide unequivocal evidence that Suc is the principal C source and that
      SuSy is the main enzyme active in Suc breakdown in roots of maize seedlings
      deprived of O2. In this situation, SuSy plays a critical role in anoxic
      tolerance.

PMID- 9536048
TI  - Cyst(e)ine is the transport metabolite of assimilated sulfur from bundle-sheath
      to mesophyll cells in maize leaves 
AB  - The intercellular distribution of the enzymes and metabolites of assimilatory
      sulfate reduction and glutathione synthesis was analyzed in maize (Zea mays L. cv
      LG 9) leaves. Mesophyll cells and strands of bundle-sheath cells from second
      leaves of 11-d-old maize seedlings were obtained by two different mechanical
      isolation methods. Cross-contamination of cell preparations was determined using
      ribulose bisphosphate carboxylase (EC 4.1.1.39) and nitrate reductase (EC
      1.6.6.1) as marker enzymes for bundle-sheath and mesophyll cells, respectively.
      ATP sulfurylase (EC 2.7.7.4) and adenosine 5'-phosphosulfate sulfotransferase
      activities were detected almost exclusively in the bundle-sheath cells, whereas
      GSH synthetase (EC 6.3.2.3) and cyst(e)ine, gamma-glutamylcysteine, and
      glutathione were located predominantly in the mesophyll cells. Feeding
      experiments using [35S]sulfate with intact leaves indicated that cyst(e)ine was
      the transport metabolite of reduced sulfur from bundle-sheath to mesophyll cells.
      This result was corroborated by tracer experiments, which showed that isolated
      bundle-sheath strands fed with [35S]sulfate secreted radioactive cyst(e)ine as
      the sole thiol into the resuspending medium. The results presented in this paper
      show that assimilatory sulfate reduction is restricted to the bundle-sheath
      cells, whereas the formation of glutathione takes place predominantly in the
      mesophyll cells, with cyst(e)ine functioning as a transport metabolite between
      the two cell types.

PMID- 9536050
TI  - Participation of mitochondrial metabolism in photorespiration. Reconstituted
      system of peroxisomes and mitochondria from spinach leaves 
AB  - In this study the interplay of mitochondria and peroxisomes in photorespiration
      was simulated in a reconstituted system of isolated mitochondria and peroxisomes
      from spinach (Spinacia oleracea L.) leaves. The mitochondria oxidizing glycine
      produced serine, which was reduced in the peroxisomes to glycerate. The required
      reducing equivalents were provided by the mitochondria via the malate
      oxaloacetate (OAA) shuttle, in which OAA was reduced in the mitochondrial matrix
      by NADH generated during glycine oxidation. The rate of peroxisomal glycerate
      formation, as compared with peroxisomal protein, resembled the corresponding rate
      required during leaf photosynthesis under ambient conditions. When the
      reconstituted system produced glycerate at this rate, the malate-to-OAA ratio was
      in equilibrium with a ratio of NADH/NAD of 8. 8 x 10(-3). This low ratio is in
      the same range as the ratio of NADH/NAD in the cytosol of mesophyll cells of
      intact illuminated spinach leaves, as we had estimated earlier. This result
      demonstrates that in the photorespiratory cycle a transfer of redox equivalents
      from the mitochondria to peroxisomes, as postulated from separate experiments
      with isolated mitochondria and peroxisomes, can indeed operate under conditions
      of the very low reductive state of the NADH/NAD system prevailing in the cytosol
      of mesophyll cells in a leaf during photosynthesis.

PMID- 9536051
TI  - Cloning and characterization of AtRGP1. A reversibly autoglycosylated arabidopsis
      protein implicated in cell wall biosynthesis.
AB  - A reversibly glycosylated polypeptide from pea (Pisum sativum) is thought to have
      a role in the biosynthesis of hemicellulosic polysaccharides. We have
      investigated this hypothesis by isolating a cDNA clone encoding a homolog of
      Arabidopsis thaliana, Reversibly Glycosylated Polypeptide-1 (AtRGP1), and
      preparing antibodies against the protein encoded by this gene. Polyclonal
      antibodies detect homologs in both dicot and monocot species. The patterns of
      expression and intracellular localization of the protein were examined. AtRGP1
      protein and RNA concentration are highest in roots and suspension-cultured cells.
      Localization of the protein shows it to be mostly soluble but also peripherally
      associated with membranes. We confirmed that AtRGP1 produced in Escherichia coli
      could be reversibly glycosylated using UDP-glucose and UDP-galactose as
      substrates. Possible sites for UDP-sugar binding and glycosylation are discussed.
      Our results are consistent with a role for this reversibly glycosylated
      polypeptide in cell wall biosynthesis, although its precise role is still
      unknown.

PMID- 9536052
TI  - Parallel changes in H2O2 and catalase during thermotolerance induced by salicylic
      acid or heat acclimation in mustard seedlings 
AB  - Spraying mustard (Sinapis alba L.) seedlings with salicylic acid (SA) solutions
      between 10 and 500 &mgr;m significantly improved their tolerance to a subsequent
      heat shock at 55 degreesC for 1.5 h. The effects of SA were concentration
      dependent, with higher concentrations failing to induce thermotolerance. The time
      course of thermotolerance induced by 100 &mgr;m SA was similar to that obtained
      with seedlings acclimated at 45 degreesC for 1 h. We examined the hypothesis that
      induced thermotolerance involved H2O2. Heat shock at 55 degreesC caused a
      significant increase in endogenous H2O2 and reduced catalase activity. A peak in
      H2O2 content was observed within 5 min of either SA treatment or transfer to the
      45 degreesC acclimation temperature. Between 2 and 3 h after SA treatment or heat
      acclimation, both H2O2 and catalase activity significantly decreased below
      control levels. The lowered H2O2 content and catalase activity occurred in the
      period of maximum thermoprotection. It is suggested that thermoprotection
      obtained either by spraying SA or by heat acclimation may be achieved by a common
      signal transduction pathway involving an early increase in H2O2.

PMID- 9536053
TI  - Soybean lipoxygenase-1 oxidizes 3Z-nonenal. A route to 4s-hydroperoxy-2e-nonenal
      and related products 
AB  - In previous work with soybean (Glycine max), it was reported that the initial
      product of 3Z-nonenal (NON) oxidation is 4-hydroperoxy-2E-nonenal (4-HPNE). 4
      HPNE can be converted to 4-hydroxy-2E-nonenal by a hydroperoxide-dependent
      peroxygenase. In the present work we have attempted to purify the 4-HPNE
      producing oxygenase from soybean seed. Chromatography on various supports had
      shown that O2 uptake with NON substrate consistently coincided with lipoxygenase
      (LOX)-1 activity. Compared with oxidation of LOX's preferred substrate, linoleic
      acid, the activity with NON was about 400- to 1000-fold less. Rather than
      obtaining the expected 4-HPNE, 4-oxo-2E-nonenal was the principal product of NON
      oxidation, presumably arising from the enzyme-generated alkoxyl radical of 4
      HPNE. In further work a precipitous drop in activity was noted upon dilution of
      LOX-1 concentration; however, activity could be enhanced by spiking the reaction
      with 13S-hydroperoxy-9Z, 11E-octadecadienoic acid. Under these conditions the
      principal product of NON oxidation shifted to the expected 4-HPNE. 4-HPNE was
      demonstrated to be 83% of the 4S-hydroperoxy-stereoisomer. Therefore, LOX-1 is
      also a 3Z-alkenal oxygenase, and it exerts the same stereospecificity of
      oxidation as it does with polyunsaturated fatty acids. Two other LOX isozymes of
      soybean seed were also found to oxidize NON to 4-HPNE with an excess of 4S
      hydroperoxy-stereoisomer.

PMID- 9536055
TI  - Comparative biochemistry of the oxidative burst produced by rose and french bean
      cells reveals two distinct mechanisms 
AB  - Cultured cells of rose (Rosa damascena) treated with an elicitor derived from
      Phytophthora spp. and suspension-cultured cells of French bean (Phaseolus
      vulgaris) treated with an elicitor derived from the cell walls of Colletotrichum
      lindemuthianum both produced H2O2. It has been hypothesized that in rose cells
      H2O2 is produced by a plasma membrane NAD(P)H oxidase (superoxide synthase),
      whereas in bean cells H2O2 is derived directly from cell wall peroxidases
      following extracellular alkalinization and the appearance of a reductant. In the
      rose/Phytophthora spp. system treated with N, N-diethyldithiocarbamate,
      superoxide was detected by a N, N'-dimethyl-9,9'-biacridium dinitrate-dependent
      chemiluminescence; in contrast, in the bean/C. lindemuthianum system, no
      superoxide was detected, with or without N,N-diethyldithiocarbamate. When rose
      cells were washed free of medium (containing cell wall peroxidase) and then
      treated with Phytophthora spp. elicitor, they accumulated a higher maximum
      concentration of H2O2 than when treated without the washing procedure. In
      contrast, a washing treatment reduced the H2O2 accumulated by French bean cells
      treated with C. lindemuthianum elicitor. Rose cells produced reductant capable of
      stimulating horseradish (Armoracia lapathifolia) peroxidase to form H2O2 but did
      not have a peroxidase capable of forming H2O2 in the presence of reductant. Rose
      and French bean cells thus appear to be responding by different mechanisms to
      generate the oxidative burst.

PMID- 9536054
TI  - Characterization of a gene for spinach CAP160 and expression of two spinach cold
      acclimation proteins in tobacco.
AB  - The cDNA sequence for CAP160, an acidic protein previously linked with cold
      acclimation in spinach (Spinacia oleracea L.), was characterized and found to
      encode a novel acidic protein of 780 amino acids having very limited homology to
      a pair of Arabidopsis thaliana stress-regulated proteins, rd29A and rd29B. The
      lack of similarity in the structural organization of the spinach and Arabidopsis
      genes highlights the absence of a high degree of conservation of this cold-stress
      gene across taxonomic boundaries. The protein has several unique motifs that may
      relate to its function during cold stress. Expression of the CAP160 mRNA was
      increased by low-temperature exposure and water stress in a manner consistent
      with a probable function during stresses that involve dehydration. The coding
      sequences for CAP160 and CAP85, another spinach cold-stress protein, were
      introduced into tobacco (Nicotiana tabacum) under the control of the 35S promoter
      using Agrobacterium tumefaciens-based transformation. Tobacco plants expressing
      the proteins individually or coexpressing both proteins were evaluated for
      relative freezing-stress tolerance. The killing temperature for 50% of the cells
      of the transgenic plants was not different from that of the wild-type plants. As
      determined by a more sensitive time/temperature kinetic study, plants expressing
      the spinach proteins had slightly lower levels of electrolyte leakage than wild
      type plants, indicative of a small reduction of freezing-stress injury. Clearly,
      the heterologous expression of two cold-stress proteins had no profound influence
      on stress tolerance, a result that is consistent with the quantitative nature of
      cold-stress-tolerance traits.

PMID- 9536056
TI  - Nuclear-gene mutations suppress a defect in the expression of the chloroplast
      encoded large subunit of ribulose-1,5-bisphosphate Carboxylase/Oxygenase 
AB  - The green alga Chlamydomonas reinhardtii mutant 76-5EN lacks photosynthesis
      because of a nuclear-gene mutation that specifically inhibits expression of the
      chloroplast gene encoding the large subunit of ribulose-1,5-bisphosphate
      carboxylase/oxygenase (Rubisco; EC 4.1.1.39). Photosynthesis-competent revertants
      were selected from mutant 76-5EN to explore the possibility of increasing Rubisco
      expression. Genetic analysis of 10 revertants revealed that most arose from
      suppressor mutations in nuclear genes distinct from the original 76-5EN mutant
      gene. The revertant strains have regained various levels of Rubisco holoenzyme,
      but none of the suppressor mutations increased Rubisco expression above the wild
      type level in either the presence or absence of the 76-5EN mutation. One
      suppressor mutation, S107-4B, caused a temperature-conditional, photosynthesis
      deficient phenotype in the absence of the original 76-5EN mutation. The S107-4B
      strain was unable to grow photosynthetically at 35 degreesC, but it expressed a
      substantial level of Rubisco holoenzyme. Whereas the 76-5EN gene encodes a
      nuclear factor that appears to be required for the transcription of the Rubisco
      large-subunit gene, the S107-4B nuclear gene may be required for the expression
      of other chloroplast genes.

PMID- 9536057
TI  - Development, Characterization, and Application of a Cadmium-Selective
      Microelectrode for the Measurement of Cadmium Fluxes in Roots of Thlaspi Species
      and Wheat
AB  - A Cd2+-selective vibrating microelectrode was constructed using a neutral carrier
      based Cd ionophore to investigate ion-transport processes along the roots of
      wheat (Triticum aestivum L.) and two species of Thlaspi, one a Zn/Cd
      hyperaccumulator and the other a related nonaccumulator. In simple Cd(NO3)2
      solutions, the electrode exhibited a Nernstian response in solutions with Cd2+
      activities as low as 50 nm. Addition of Ca2+ to the calibration solutions did not
      influence the slope of the calibration curve but reduced the detection limit to a
      solution activity of 1 um Cd2+. Addition of high concentrations of K+ and Mg2+ to
      the calibration solution to mimic the ionic composition of the cytoplasm affected
      neither the slope nor the sensitivity of the electrode, demonstrating the pH
      insensitive electrode's potential for intracellular investigations. The electrode
      was assayed for selectivity and was shown to be at least 1000 times more
      selective for Cd2+ than for any of those potentially interfering ions tested.
      Flux measurements along the roots of the two Thlaspi species showed no
      differences in the pattern or the magnitude of Cd2+ uptake within the time frame
      considered. The Cd2+-selective microelectrode will permit detailed investigations
      of heavy-metal ion transport in plant roots, especially in the area of
      phytoremediation.

PMID- 9536058
TI  - Root growth and oxygen relations at low water potentials. Impact Of oxygen
      availability in polyethylene glycol solutions 
AB  - Polyethylene glycol (PEG), which is often used to impose low water potentials
      (psiw) in solution culture, decreases O2 movement by increasing solution
      viscosity. We investigated whether this property causes O2 deficiency that
      affects the elongation or metabolism of maize (Zea mays L.) primary roots.
      Seedlings grown in vigorously aerated PEG solutions at ambient solution O2
      partial pressure (pO2) had decreased steady-state root elongation rates,
      increased root-tip alanine concentrations, and decreased root-tip proline
      concentrations relative to seedlings grown in PEG solutions of above-ambient pO2
      (alanine and proline accumulation are responses to hypoxia and low psiw,
      respectively). Measurements of root pO2 were made using an O2 microsensor to
      ensure that increased solution pO2 did not increase root pO2 above physiological
      levels. In oxygenated PEG solutions that gave maximal root elongation rates, root
      pO2 was similar to or less than (depending on depth in the tissue) pO2 of roots
      growing in vermiculite at the same psiw. Even without PEG, high solution pO2 was
      necessary to raise root pO2 to the levels found in vermiculite-grown roots.
      Vermiculite was used for comparison because it has large air spaces that allow
      free movement of O2 to the root surface. The results show that supplemental
      oxygenation is required to avoid hypoxia in PEG solutions. Also, the data suggest
      that the O2 demand of the root elongation zone may be greater at low relative to
      high psiw, compounding the effect of PEG on O2 supply. Under O2-sufficient
      conditions root elongation was substantially less sensitive to the low psiw
      imposed by PEG than that imposed by dry vermiculite.

PMID- 9536059
TI  - Characterization of cadmium binding, uptake, and translocation in intact
      seedlings of bread and durum wheat cultivars 
AB  - High Cd content in durum wheat (Triticum turgidum L. var durum) grain grown in
      the United States and Canada presents potential health and economic problems for
      consumers and growers. In an effort to understand the biological processes that
      result in excess Cd accumulation, root Cd uptake and xylem translocation to
      shoots in seedlings of bread wheat (Triticum aestivum L.) and durum wheat
      cultivars were studied. Whole-plant Cd accumulation was somewhat greater in the
      bread wheat cultivar, but this was probably because of increased apoplastic Cd
      binding. Concentration-dependent 109Cd2+-influx kinetics in both cultivars were
      characterized by smooth, nonsaturating curves that could be dissected into linear
      and saturable components. The saturable component likely represented carrier
      mediated Cd influx across root-cell plasma membranes (Michaelis constant, 20-40
      nm; maximum initial velocity, 26-29 nmol g-1 fresh weight h-1), whereas linear Cd
      uptake represented cell wall binding of 109Cd. Cd translocation to shoots was
      greater in the bread wheat cultivar than in the durum cultivar because a larger
      proportion of root-absorbed Cd moved to shoots. Our results indicate that excess
      Cd accumulation in durum wheat grain is not correlated with seedling-root influx
      rates or root-to-shoot translocation, but may be related to phloem-mediated Cd
      transport to the grain.

PMID- 9536061
TI  - Extracellular matrix assembly in diatoms (Bacillariophyceae). Iii. Organization
      Of fucoglucuronogalactans within the adhesive stalks of achnanthes longipes 
AB  - Achnanthes longipes is a marine, biofouling diatom that adheres to surfaces via
      adhesive polymers extruded during motility or organized into structures called
      stalks that contain three distinct regions: the pad, shaft, and collar. Four
      monoclonal antibodies (AL.C1-AL.C4) and antibodies from two uncloned hybridomas
      (AL.E1 and AL.E2) were raised against the extracellular adhesives of A. longipes.
      Antibodies were screened against a hot-water-insoluble/hot-bicarbonate-soluble
      fraction. The hot-water-insoluble/hot-bicarbonate-soluble fraction was
      fractionated to yield polymers in three size ranges: F1, >/= 20,000, 000 Mr; F2,
      congruent with100,000 Mr; and F3, <10,000 Mr relative to dextran standards. The
      congruent with100,000-Mr fraction consisted of highly sulfated (approximately
      11%) fucoglucuronogalactans (FGGs) and low-sulfate (approximately 2%) FGGs,
      whereas F1 was composed of O-linked FGG (F2)-polypeptide (F3) complexes. AL.C1,
      AL.C2, AL.C4, AL.E1, and AL.E2 recognized carbohydrate complementary regions on
      FGGs, with antigenicity dependent on fucosyl-containing side chains. AL.C3 was
      unique in that it had a lower affinity for FGGs and did not label any portion of
      the shaft. Enzyme-linked immunosorbent assay and immunocytochemistry indicated
      that low-sulfate FGGs are expelled from pores surrounding the raphe terminus,
      creating the cylindrical outer layers of the shaft, and that highly sulfated FGGs
      are extruded from the raphe, forming the central core. Antibody-labeling patterns
      and other evidence indicated that the shaft central-core region is related to
      material exuded from the raphe during cell motility.

PMID- 9536060
TI  - Actin-bundling protein isolated from pollen tubes of lily. Biochemical and
      immunocytochemical characterization 
AB  - A 135-kD actin-bundling protein was purified from pollen tubes of lily (Lilium
      longiflorum) using its affinity to F-actin. From a crude extract of the pollen
      tubes, this protein was coprecipitated with exogenously added F-actin and then
      dissociated from F-actin by treating it with high-ionic-strength solution. The
      protein was further purified sequentially by chromatography on a hydroxylapatite
      column, a gel-filtration column, and a diethylaminoethyl-cellulose ion-exchange
      column. In the present study, this protein is tentatively referred to as P-135
      ABP (Plant 135-kD Actin-Bundling Protein). By the elution position from a gel
      filtration column, we estimated the native molecular mass of purified P-135-ABP
      to be 260 kD, indicating that it existed in a dimeric form under physiological
      conditions. This protein bound to and bundled F-actin prepared from chicken
      breast muscle in a Ca2+-independent manner. The binding of 135-P-ABP to actin was
      saturated at an approximate stoichiometry of 26 actin monomers to 1 dimer of P
      135-ABP. By transmission electron microscopy of thin sections, we observed cross
      bridges between F-actins with a longitudinal periodicity of 31 nm.
      Immunofluorescence microscopy using rhodamine-phalloidin and antibodies against
      the 135-kD polypeptide showed that P-135-ABP was colocalized with bundles of
      actin filaments in lily pollen tubes, leading us to conclude that it is the
      factor responsible for bundling the filaments.

PMID- 9536062
TI  - Partial purification and characterization of the maize mitochondrial pyruvate
      dehydrogenase complex 
AB  - The pyruvate dehydrogenase complex was partially purified and characterized from
      etiolated maize (Zea mays L.) shoot mitochondria. Analysis by sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis showed proteins of 40, 43, 52 to 53,
      and 62 to 63 kD. Immunoblot analyses identified these proteins as the E1beta-,
      E1alpha-, E2-, and E3-subunits, respectively. The molecular mass of maize E2 is
      considerably smaller than that of other plant E2 subunits (76 kD). The activity
      of the maize mitochondrial complex has a pH optimum of 7.5 and a divalent cation
      requirement best satisfied by Mg2+. Michaelis constants for the substrates were
      47, 3, 77, and 1 &mgr;m for pyruvate, coenzyme A (CoA), NAD+, and thiamine
      pyrophosphate, respectively. The products NADH and acetyl-CoA were competitive
      inhibitors with respect to NAD+ and CoA, and the inhibition constants were 15 and
      47 &mgr;m, respectively. The complex was inactivated by phosphorylation and was
      reactivated after the removal of ATP and the addition of Mg2+.

PMID- 9536063
TI  - Polypeptides of the maize amyloplast stroma. Stromal localization of starch
      biosynthetic enzymes and identification of an 81-kilodalton amyloplast stromal
      heat-shock cognate.
AB  - In the developing endosperm of monocotyledonous plants, starch granules are
      synthesized and deposited within the amyloplast. A soluble stromal fraction was
      isolated from amyloplasts of immature maize (Zea mays L.) endosperm and analyzed
      for enzyme activities and polypeptide content. Specific activities of starch
      synthase and starch-branching enzyme (SBE), but not the cytosolic marker alcohol
      dehydrogenase, were strongly enhanced in soluble amyloplast stromal fractions
      relative to soluble extracts obtained from homogenized kernels or endosperms.
      Immunoblot analysis demonstrated that starch synthase I, SBEIIb, and sugary1, the
      putative starch-debranching enzyme, were each highly enriched in the amyloplast
      stroma, providing direct evidence for the localization of starch-biosynthetic
      enzymes within this compartment. Analysis of maize mutants shows the deficiency
      of the 85-kD SBEIIb polypeptide in the stroma of amylose extender cultivars and
      that the dull mutant lacks a >220-kD stromal polypeptide. The stromal fraction is
      distinguished by differential enrichment of a characteristic group of previously
      undocumented polypeptides. N-terminal sequence analysis revealed that an abundant
      81-kD stromal polypeptide is a member of the Hsp70 family of stress-related
      proteins. Moreover, the 81-kD stromal polypeptide is strongly recognized by
      antibodies specific for an Hsp70 of the chloroplast stroma. These findings are
      discussed in light of implications for the correct folding and assembly of
      soluble, partially soluble, and granule-bound starch-biosynthetic enzymes during
      import into the amyloplast.

PMID- 9536064
TI  - Three drought-responsive members of the nonspecific lipid-transfer protein gene
      family in Lycopersicon pennellii show different developmental patterns of
      expression.
AB  - Genomic clones of two nonspecific lipid-transfer protein genes from a drought
      tolerant wild species of tomato (Lycopersicon pennellii Corr.) were isolated
      using as a probe a drought- and abscisic acid (ABA)-induced cDNA clone (pLE16)
      from cultivated tomato (Lycopersicon esculentum Mill.). Both genes (LpLtp1 and
      LpLtp2) were sequenced and their corresponding mRNAs were characterized; they are
      both interrupted by a single intron at identical positions and predict basic
      proteins of 114 amino acid residues. Genomic Southern data indicated that these
      genes are members of a small gene family in Lycopersicon spp. The 3'-untranslated
      regions from LpLtp1 and LpLtp2, as well as a polymerase chain reaction-amplified
      3'-untranslated region from pLE16 (cross-hybridizing to a third gene in L.
      pennellii, namely LpLtp3), were used as gene-specific probes to describe
      expression in L. pennellii through northern-blot analyses. All LpLtp genes were
      exclusively expressed in the aerial tissues of the plant and all were drought and
      ABA inducible. Each gene had a different pattern of expression in fruit, and
      LpLtp1 and LpLtp2, unlike LpLtp3, were both primarily developmentally regulated
      in leaf tissue. Putative ABA-responsive elements were found in the proximal
      promoter regions of LpLtp1 and LpLtp2.

PMID- 9536065
TI  - Structure and expression of a dhurrinase (beta-glucosidase) from sorghum.
AB  - Sorghum (Sorghum bicolor L. Moench) has two isozymes of the cyanogenic beta
      glucosidase dhurrinase: dhurrinase-1 (Dhr1) and dhurrinase-2 (Dhr2). A nearly
      full-length cDNA encoding dhurrinase was isolated from 4-d-old etiolated
      seedlings and sequenced. The cDNA has a 1695-nucleotide-long open reading frame,
      which codes for a 565-amino acid-long precursor and a 514-amino acid-long mature
      protein, respectively. Deduced amino acid sequence of the sorghum Dhr showed 70%
      identity with two maize (Zea mays) beta-glucosidase isozymes. Southern-blot data
      suggested that beta-glucosidase is encoded by a small multigene family in
      sorghum. Northern-blot data indicated that the mRNA corresponding to the cloned
      Dhr cDNA is present at high levels in the node and upper half of the mesocotyl in
      etiolated seedlings but at low levels in the root-only in the zone of elongation
      and the tip region. Light-grown seedling parts had lower levels of Dhr mRNA than
      those of etiolated seedlings. Immunoblot analysis performed using maize-anti-beta
      glucosidase sera detected two distinct dhurrinases (57 and 62 kD) in sorghum. The
      distribution of Dhr activity in different plant parts supports the mRNA and
      immunoreactive protein data, suggesting that the cloned cDNA corresponds to the
      Dhr1 (57 kD) isozyme and that the dhr1 gene shows organ-specific expression.

PMID- 9536066
TI  - Accumulation of a clock-regulated transcript during flower-inductive darkness in
      pharbitis nil 
AB  - To clarify the molecular basis of the photoperiodic induction of flowering in the
      short-day plant Pharbitis nil cv Violet, we examined changes in the level of mRNA
      in cotyledons during the flower-inductive photoperiod using the technique of
      differential display by the polymerase chain reaction. A transcript that
      accumulated during the inductive dark period was identified and a cDNA
      corresponding to the transcript, designated PnC401 (P. nil C401), was isolated.
      RNA-blot hybridization verified that levels of PnC401 mRNA fluctuated with a
      circadian rhythm, with maxima between 12 and 16 h after the beginning of the dark
      period) and minima of approximately 0. This oscillation continued even during an
      extended dark period but was damped under continuous light. Accumulation of
      PnC401 mRNA was reduced by a brief exposure to red light at the 8th h of the dark
      period (night-break treatment) or by exposure to far-red light at the end of the
      light period (end-of-day far-red treatment). These results suggest that
      fluctuations in levels of PnC401 mRNA are regulated by phytochrome(s) and a
      circadian clock and that they are associated with photoperiodic events that
      include induction of flowering.

PMID- 9536067
TI  - Reversibility of H+-ATPase and H+-pyrophosphatase in tonoplast vesicles from
      maize coleoptiles and seeds 
AB  - Tonoplast-enriched vesicles isolated from maize (Zea mays L.) coleoptiles and
      seeds synthesize ATP from ADP and inorganic phosphate (Pi) and inorganic
      pyrophosphate from Pi. The synthesis is consistent with reversal of the catalytic
      cycle of the H+-ATPase and H+-pyrophosphatase (PPase) vacuolar membrane-bound
      enzymes. This was monitored by measuring the exchange reaction that leads to 32Pi
      incorporation into ATP or inorganic pyrophosphate. The reversal reactions of
      these enzymes were dependent on the proton gradient formed across the vesicle
      membrane and were susceptible to the uncoupler carbonyl cyanide
      p(trifluoromethoxy)-phenylhydrazone and the detergent Triton X-100. Comparison of
      the two H+ pumps showed that the H+-ATPase was more active than H+-PPase in
      coleoptile tonoplast vesicles, whereas in seed vesicles H+-PPase activity was
      clearly dominant. These findings may reflect the physiological significance of
      these enzymes in different tissues at different stages of development and/or
      differentiation.

PMID- 9536068
TI  - Regulation of oleoresinosis in grand fir (Abies grandis). Differential
      transcriptional control of monoterpene, sesquiterpene, and diterpene synthase
      genes in response to wounding 
AB  - Grand fir (Abies grandis Lindl.) has been developed as a model system for the
      study of wound-induced oleoresinosis in conifers as a response to insect attack.
      Oleoresin is a roughly equal mixture of turpentine (85% monoterpenes [C10] and
      15% sesquiterpenes [C15]) and rosin (diterpene [C20] resin acids) that acts to
      seal wounds and is toxic to both invading insects and their pathogenic fungal
      symbionts. The dynamic regulation of wound-induced oleoresin formation was
      studied over 29 d at the enzyme level by in vitro assay of the three classes of
      synthases directly responsible for the formation of monoterpenes, sesquiterpenes,
      and diterpenes from the corresponding C10, C15, and C20 prenyl diphosphate
      precursors, and at the gene level by RNA-blot hybridization using terpene
      synthase class-directed DNA probes. In overall appearance, the shapes of the time
      course curves for all classes of synthase activities are similar, suggesting
      coordinate formation of all of the terpenoid types. However, closer inspection
      indicates that the monoterpene synthases arise earlier, as shown by an
      abbreviated time course over 6 to 48 h. RNA-blot analyses indicated that the
      genes for all three classes of enzymes are transcriptionally activated in
      response to wounding, with the monoterpene synthases up-regulated first
      (transcripts detectable 2 h after wounding), in agreement with the results of
      cell-free assays of monoterpene synthase activity, followed by the coordinately
      regulated sesquiterpene synthases and diterpene synthases (transcription
      beginning on d 3-4). The differential timing in the production of oleoresin
      components of this defense response is consistent with the immediate formation of
      monoterpenes to act as insect toxins and their later generation at solvent levels
      for the mobilization of resin acids responsible for wound sealing.

PMID- 9536069
TI  - Dim-red-light-induced increase in polar auxin transport in cucumber seedlings. I.
      Development Of altered capacity, velocity, and response to inhibitors 
AB  - We have developed and characterized a system to analyze light effects on auxin
      transport independent of photosynthetic effects. Polar transport of [3H]indole-3
      acetic acid through hypocotyl segments from etiolated cucumber (Cucumis sativus
      L.) seedlings was increased in seedlings grown in dim-red light (DRL) (0.5
      &mgr;mol m-2 s-1) relative to seedlings grown in darkness. Both transport
      velocity and transport intensity (export rate) were increased by at least a
      factor of 2. Tissue formed in DRL completely acquired the higher transport
      capacity within 50 h, but tissue already differentiated in darkness acquired only
      a partial increase in transport capacity within 50 h of DRL, indicating a
      developmental window for light induction of commitment to changes in auxin
      transport. This light-induced change probably manifests itself by alteration of
      function of the auxin efflux carrier, as revealed using specific transport
      inhibitors. Relative to dark controls, DRL-grown seedlings were differentially
      less sensitive to two inhibitors of polar auxin transport, N-(naphth-1-yl)
      phthalamic acid and 2,3,5-triiodobenzoic acid. On the basis of these data, we
      propose that the auxin efflux carrier is a key target of light regulation during
      photomorphogenesis.

PMID- 9536070
TI  - Analysis of cell division and elongation underlying the developmental
      acceleration of root growth in Arabidopsis thaliana.
AB  - To investigate the relation between cell division and expansion in the regulation
      of organ growth rate, we used Arabidopsis thaliana primary roots grown vertically
      at 20 degreesC with an elongation rate that increased steadily during the first
      14 d after germination. We measured spatial profiles of longitudinal velocity and
      cell length and calculated parameters of cell expansion and division, including
      rates of local cell production (cells mm-1 h-1) and cell division (cells cell-1 h
      1). Data were obtained for the root cortex and also for the two types of
      epidermal cell, trichoblasts and atrichoblasts. Accelerating root elongation was
      caused by an increasingly longer growth zone, while maximal strain rates remained
      unchanged. The enlargement of the growth zone and, hence, the accelerating root
      elongation rate, were accompanied by a nearly proportionally increased cell
      production. This increased production was caused by increasingly numerous
      dividing cells, whereas their rates of division remained approximately constant.
      Additionally, the spatial profile of cell division rate was essentially constant.
      The meristem was longer than generally assumed, extending well into the region
      where cells elongated rapidly. In the two epidermal cell types, meristem length
      and cell division rate were both very similar to that of cortical cells, and
      differences in cell length between the two epidermal cell types originated at the
      apex of the meristem. These results highlight the importance of controlling the
      number of dividing cells, both to generate tissues with different cell lengths
      and to regulate the rate of organ enlargement.

PMID- 9536071
TI  - Evidence for 1-(Malonylamino)cyclopropane-1-carboxylic acid being the major
      conjugate of aminocyclopropane-1-carboxylic acid in tomato fruit 
AB  - Tomato (Lycopersicon esculentum Miller) fruit discs fed with [2, 3-14C]1
      aminocyclopropane-1-carboxylic acid (ACC) formed 1-malonyl-ACC (MACC) as the
      major conjugate of ACC in fruit throughout all ripening stages, from immature
      green through the red-ripe stage. Another conjugate of ACC, gamma-glutamyl-ACC
      (GACC), was formed only in mature-green fruit in an amount about 10% of that of
      MACC; conjugation of ACC into GACC was not detected in fruits at other ripening
      stages. No GACC formation was observed from etiolated mung bean (Vigna radiata
      [L.] Wilczek) hypocotyls, etiolated common vetch (Vicia sativum L.) epicotyls, or
      pea (Pisum sativum L.) root tips, etiolated epicotyls, and green stem tissue,
      where active conversion of ACC into MACC was observed. GACC was, however, formed
      in vitro in extracts from fruit of all ripening stages. GACC formation in an
      extract from red fruit at pH 7.15 was only about 3% of that at pH 8.0, the pH at
      which most assays were run. Our present in vivo data support the previous
      contention that MACC is the major conjugate of ACC in plant tissues, whereas GACC
      is a minor, if any, conjugate of ACC. Thus, our data do not support the proposal
      that GACC formation could be more important than MACC formation in tomato fruit.

PMID- 9536072
TI  - Different phototransduction kinetics of phytochrome A and phytochrome B in
      Arabidopsis thaliana.
AB  - The kinetics of phototransduction of phytochrome A (phyA) and phytochrome B
      (phyB) were compared in etiolated Arabidopsis thaliana seedlings. The responses
      of hypocotyl growth, cotyledon unfolding, and expression of a light-harvesting
      chlorophyll a/b-binding protein of the photosystem II gene promoter fused to the
      coding region of beta-glucuronidase (used as a reporter enzyme) were mediated by
      phyA under continuous far-red light (FR) and by phyB under continuous red light
      (R). The seedlings were exposed hourly either to n min of FR followed by 60 minus
      n min in darkness or to n min of R, 3 min of FR (to back-convert phyB to its
      inactive form), and 57 minus n min of darkness. For the three processes
      investigated here, the kinetics of phototransduction of phyB were faster than
      that of phyA. For instance, 15 min R h-1 (terminated with a FR pulse) were almost
      as effective as continuous R, whereas 15 min of FR h-1 caused less than 30% of
      the effect of continuous FR. This difference is interpreted in terms of
      divergence of signal transduction pathways downstream from phyA and phyB.

PMID- 9536074
TI  - Photosystem II cyclic heterogeneity and photoactivation in the diazotrophic,
      unicellular cyanobacterium cyanothece species ATCC 51142 
AB  - The unicellular, diazotrophic cyanobacterium Cyanothece sp. ATCC 51142
      demonstrated important modifications to photosystem II (PSII) centers when grown
      under light/dark N2-fixing conditions. The properties of PSII were studied
      throughout the diurnal cycle using O2-flash-yield and pulse-amplitude-modulated
      fluorescence techniques. Nonphotochemical quenching (qN) of PSII increased during
      N2 fixation and persisted after treatments known to induce transitions to state
      1. The qN was high in cells grown in the dark, and then disappeared progressively
      during the first 4 h of light growth. The photoactivation probability, epsilon,
      demonstrated interesting oscillations, with peaks near 3 h of darkness and 4 and
      10 h of light. Experiments and calculations of the S-state distribution indicated
      that PSII displays a high level of heterogeneity, especially as the cells prepare
      for N2 fixation. We conclude that the oxidizing side of PSII is strongly affected
      during the period before and after the peak of nitrogenase activity; changes
      include a lowered capacity for O2 evolution, altered dark stability of PSII
      centers, and substantial changes in qN.

PMID- 9536073
TI  - Genes involved in osmoregulation during turgor-driven cell expansion of
      developing cotton fibers are differentially regulated.
AB  - Cotton (Gossypium hirsutum L.) fibers are single-celled trichomes that
      synchronously undergo a phase of rapid cell expansion, then a phase including
      secondary cell wall deposition, and finally maturation. To determine if there is
      coordinated regulation of gene expression during fiber expansion, we analyzed the
      expression of components involved in turgor regulation and a cytoskeletal protein
      by measuring levels of mRNA and protein accumulation and enzyme activity.
      Fragments of the genes for the plasma membrane proton-translocating ATPase,
      vacuole-ATPase, proton-translocating pyrophosphatase (PPase), phosphoenolpyruvate
      carboxylase, major intrinsic protein, and alpha-tubulin were amplified by
      polymerase chain reaction and used as probes in ribonuclease protection assays of
      RNA from a fiber developmental series, revealing two discrete patterns of mRNA
      accumulation. Transcripts of all but the PPase accumulated to highest levels
      during the period of peak expansion (+12-15 d postanthesis [dpa]), then declined
      with the onset of secondary cell wall synthesis. The PPase was constitutively
      expressed through fiber development. Activity of the two proton-translocating
      ATPases peaked at +15 dpa, whereas PPase activity peaked at +20 dpa, suggesting
      that all are involved in the process of cell expansion but with varying roles.
      Patterns of protein accumulation and enzyme activity for some of the proteins
      examined suggest posttranslational regulation through fiber development.

PMID- 9536075
TI  - Surface localization of zein storage proteins in starch granules from maize
      endosperm. Proteolytic removal by thermolysin and in vitro cross-linking of
      granule-associated polypeptides.
AB  - Starch granules from maize (Zea mays) contain a characteristic group of
      polypeptides that are tightly associated with the starch matrix (C. Mu-Forster,
      R. Huang, J.R. Powers, R.W. Harriman, M. Knight, G.W. Singletary, P.L. Keeling,
      B.P. Wasserman [1996] Plant Physiol 111: 821-829). Zeins comprise about 50% of
      the granule-associated proteins, and in this study their spatial distribution
      within the starch granule was determined. Proteolysis of starch granules at
      subgelatinization temperatures using the thermophilic protease thermolysin led to
      selective removal of the zeins, whereas granule-associated proteins of 32 kD or
      above, including the waxy protein, starch synthase I, and starch-branching enzyme
      IIb, remained refractory to proteolysis. Granule-associated proteins from maize
      are therefore composed of two distinct classes, the surface-localized zeins of 10
      to 27 kD and the granule-intrinsic proteins of 32 kD or higher. The origin of
      surface-localized delta-zein was probed by comparing delta-zein levels of starch
      granules obtained from homogenized whole endosperm with granules isolated from
      amyloplasts. Starch granules from amyloplasts contained markedly lower levels of
      delta-zein relative to granules prepared from whole endosperm, thus indicating
      that delta-zein adheres to granule surfaces after disruption of the amyloplast
      envelope. Cross-linking experiments show that the zeins are deposited on the
      granule surface as aggregates. In contrast, the granule-intrinsic proteins are
      prone to covalent modification, but do not form intermolecular cross-links. We
      conclude that individual granule intrinsic proteins exist as monomers and are not
      deposited in the form of multimeric clusters within the starch matrix.

PMID- 9536077
TI  - The intracellular localization of ribulose-1,5-bisphosphate Carboxylase/Oxygenase
      in chlamydomonas reinhardtii 
AB  - The pyrenoid is a proteinaceous structure found in the chloroplast of most
      unicellular algae. Various studies indicate that ribulose-1, 5-bisphosphate
      carboxylase/oxygenase (Rubisco) is present in the pyrenoid, although the fraction
      of Rubisco localized there remains controversial. Estimates of the amount of
      Rubisco in the pyrenoid of Chlamydomonas reinhardtii range from 5% to nearly
      100%. Using immunolocalization, the amount of Rubisco localized to the pyrenoid
      or to the chloroplast stroma was estimated for C. reinhardtii cells grown under
      different conditions. It was observed that the amount of Rubisco in the pyrenoid
      varied with growth condition; about 40% was in the pyrenoid when the cells were
      grown under elevated CO2 and about 90% with ambient CO2. In addition, it is
      likely that pyrenoidal Rubisco is active in CO2 fixation because in vitro
      activity measurements showed that most of the Rubisco must be active to account
      for CO2-fixation rates observed in whole cells. These results are consistent with
      the idea that the pyrenoid is the site of CO2 fixation in C. reinhardtii and
      other unicellular algae containing CO2-concentrating mechanisms.

PMID- 9536076
TI  - Differential regulation of sugar-sensitive sucrose synthases by hypoxia and
      anoxia indicate complementary transcriptional and posttranscriptional responses 
AB  - The goal of this research was to resolve the hypoxic and anoxic responses of
      maize (Zea mays) sucrose (Suc) synthases known to differ in their sugar
      regulation. The two maize Suc synthase genes, Sus1 and Sh1, both respond to sugar
      and O2, and recent work suggests commonalities between these signaling systems.
      Maize seedlings (NK508 hybrid, W22 inbred, and an isogenic sh1-null mutant) were
      exposed to anoxic, hypoxic, and aerobic conditions (0, 3, and 21% O2,
      respectively), when primary roots had reached approximately 5 cm. One-centimeter
      tips were excised for analysis during the 48-h treatments. At the mRNA level,
      Sus1 was rapidly up-regulated by hypoxia (approximately 5-fold in 6 h), whereas
      anoxia had less effect. In contrast, Sh1 mRNA abundance increased strongly under
      anoxia (approximately 5-fold in 24 h) and was much less affected by hypoxia. At
      the enzyme level, total Suc synthase activity rose rapidly under hypoxia but
      showed little significant change during anoxia. The contributions of SUS1 and SH1
      activities to these responses were dissected over time by comparing the sh1-null
      mutant with the isogenic wild type (Sus+, Sh1+). Sh1-dependent activity
      contributed most markedly to a rapid protein-level response consistently observed
      in the first 3 h, and, subsequently, to a long-term change mediated at the level
      of mRNA accumulation at 48 h. A complementary midterm rise in SUS1 activity
      varied in duration with genetic background. These data highlight the involvement
      of distinctly different genes and probable signal mechanisms under hypoxia and
      anoxia, and together with earlier work, show parallel induction of "feast and
      famine" Suc synthase genes by hypoxia and anoxia, respectively. In addition,
      complementary modes of transcriptional and posttranscriptional regulation are
      implicated by these data, and provide a mechanism for sequential contributions
      from the Sus1 and Sh1 genes during progressive onset of naturally occurring low
      O2 events.

PMID- 9536078
TI  - A cyanobacterium lacking iron superoxide dismutase is sensitized to oxidative
      stress induced with methyl viologen but Is not sensitized to oxidative stress
      induced with norflurazon 
AB  - A strain of Synechococcus sp. strain PCC 7942 with no functional Fe superoxide
      dismutase (SOD), designated sodB-, was characterized by its growth rate,
      photosynthetic pigments, and cyclic photosynthetic electron transport activity
      when treated with methyl viologen or norflurazon (NF). In their unstressed
      conditions, both the sodB- and wild-type strains had similar chlorophyll and
      carotenoid contents and catalase activity, but the wild type had a faster growth
      rate and higher cyclic electron transport activity. The sodB- was very sensitive
      to methyl viologen, indicating a specific role for the FeSOD in protection
      against superoxide generated in the cytosol. In contrast, the sodB- mutant was
      less sensitive than the wild type to oxidative stress imposed with NF. This
      suggests that the FeSOD does not protect the cell from excited singlet-state
      oxygen generated within the thylakoid membrane. Another up-regulated antioxidant,
      possibly the MnSOD, may confer protection against NF in the sodB- strain. These
      results support the hypothesis that different SODs have specific protective
      functions within the cell.

PMID- 9536079
TI  - The BCR gene recombines preferentially with Alu elements in complex BCR-ABL
      translocations of chronic myeloid leukaemia.
AB  - Chronic myeloid leukaemia (CML) develops when two genes, BCR on chromosome 22 and
      ABL on chromosome 9, recombine to form a hybrid BCR-ABL gene with leukaemogenic
      properties. The mechanism which underlies this recombination is unknown, but
      additional chromosome sites may be involved to form complex BCR-ABL
      rearrangements. The majority of breakpoints in BCR occur within a 5 kb major
      breakpoint cluster region, M-Bcr. Here, we show that the 3' part of M-Bcr
      recombined within, or immediately adjacent to, Alu elements at the additional
      sites in all five complex BCR-ABL rearrangements that have been examined so far.
      This is a new finding which suggests that Alu sequences have an affinity for the
      BCR-ABL recombination process in complex rearrangements, and provides additional
      evidence for the association of these elements with somatic rearrangements which
      cause human leukaemia. We further show that sequence motifs similar to IgH switch
      pentamers and consensus binding sites of the lymphoid-associated Translin protein
      are present on one or more participating strands at 3'M-Bcr recombination sites.
      Motifs similar to Translin-binding sites were also identified within the Alu
      consensus. Expressed sequences mapped close to the breakpoint sites on other
      chromosomes in three of the five cases examined.

PMID- 9536080
TI  - Aggregation of N-terminal huntingtin is dependent on the length of its glutamine
      repeats.
AB  - Huntington's disease (HD) is caused by expansion of a glutamine repeat in
      huntingtin. Mutant huntingtin contains 36-55 repeats in adult HD patients and >60
      repeats in juvenile HD patients. An N-terminal fragment of mutant huntingtin
      forms aggregates in neuronal nuclei in the brains of transgenic mice and HD
      patients. Aggregation of expanded polyglutamine is thought to be a common
      pathological mechanism in HD and other glutamine repeat diseases. It is not clear
      how the length of the repeats is correlated with formation of protein aggregates.
      By expressing a series of huntingtin constructs encoding various glutamine
      repeats (23-150 units) in cultured cells we observed N-terminal fragments of
      huntingtin (amino acids 1-67 and 1-212), but not full-length huntingtins, with
      glutamine repeats >/=66 units formed protein aggregates. Huntingtin aggregation
      was not induced when the repeat was </=49 units and was markedly promoted by very
      long repeats >/=120 units. This study suggests that various N-terminal fragments
      of mutant huntingtin can form aggregates and that aggregation is prompted by
      lengthening the glutamine repeat.

PMID- 9536081
TI  - Truncated N-terminal fragments of huntingtin with expanded glutamine repeats form
      nuclear and cytoplasmic aggregates in cell culture.
AB  - Huntington's disease (HD) is a progressive neurodegenerative disorder caused by
      an expanding CAG repeat coding for polyglutamine in the huntingtin protein.
      Recent data have suggested the possibility that an N-terminal fragment of
      huntingtin may aggregate in neurons of patients with HD, both in the cytoplasm,
      forming dystrophic neurites, and in the nucleus, forming intranuclear neuronal
      inclusion bodies. An animal model of HD using the short N-terminal fragment of
      huntingtin has also been found to have intranuclear inclusions and this same
      fragment can aggregate in vitro . We have now developed a cell culture model
      demonstrating that N-terminal fragments of huntingtin with expanded glutamine
      repeats aggregate both in the cytoplasm and in the nucleus. Neuroblastoma cells
      transiently transfected with full-length huntingtin constructs with either a
      normal or expanded repeat had diffuse cytoplasmic localization of the protein. In
      contrast, cells transfected with truncated N-terminal fragments showed
      aggregation only if the glutamine repeat was expanded. The aggregates were often
      ubiquitinated. The shorter truncated product appeared to form more aggregates in
      the nucleus. Cells transfected with the expanded repeat construct but not the
      normal repeat construct showed enhanced toxicity to the apoptosis-inducing agent
      staurosporine. These data indicate that N-terminal truncated fragments of
      huntingtin with expanded glutamine repeats can aggregate in cells in culture and
      that this aggregation can be toxic to cells. This model will be useful for future
      experiments to test mechanisms of aggregation and toxicity and potentially for
      testing experimental therapeutic interventions.

PMID- 9536082
TI  - Functional analysis of the Huntington's disease (HD) gene promoter.
AB  - The basis for the highly specific neuronal vulnerability seen in Huntington's
      disease (HD) has not been determined. Recent studies have demonstrated that
      variation in HD protein expression occurs in the striatum, with affected regions
      showing increased HD immunoreactivity. Experiments in HD and SCA1 transgenic mice
      suggest a correlation between phenotypic severity and expression of the mutant
      transgene. To gain insights into control of HD gene expression, and to
      investigate the possibility of cell-cell differences in transcription, we have
      analysed the 5' upstream region of the HD gene in a neuronal (SK-N-SH) and a non
      neuronal (JEG3) cell line. Reporter gene assays demonstrated the presence of a
      key positive-acting region apparently arising from two Sp1 sites in a tandem
      repeat acting synergistically. This site is polymorphic, and a single Sp1 site is
      associated with reduced levels of transcription. These experiments also reveal
      differences in control of expression between neuronal and non-neuronal cell
      lines.

PMID- 9536083
TI  - The 185delAG BRCA1 mutation originated before the dispersion of Jews in the
      diaspora and is not limited to Ashkenazim.
AB  - The 185delAG mutation in BRCA1 is detected in Ashkenazi Jews both in familial
      breast and ovarian cancer and in the general population. All tested Ashkenazi
      mutation carriers share the same allelic pattern at the BRCA1 locus. Our previous
      study showed that this 'Ashkenazi' mutation also occurs in Iraqi Jews with a
      similar allelic pattern. We extended our analysis to other non-Ashkenazi subsets:
      354 of Moroccan origin, 200 Yemenites and 150 Iranian Jews. Heteroduplex analysis
      complemented by direct DNA sequencing of abnormally migrating bands were
      employed. Four of Moroccan origin (1. 1%) and none of the Yemenites or Iranians
      was a carrier of the 185delAG mutation. BRCA1 allelic patterns were determined
      for four of these individuals and for 12 additional non-Ashkenazi 185delAG
      mutation carriers who had breast/ovarian cancer. Six non-Ashkenazi individuals
      shared the common 'Ashkenazi haplotype', four had a closely related pattern, and
      the rest ( n = 6) displayed a distinct BRCA1 allelic pattern. We conclude that
      the 185delAG BRCA1 mutation occurs in some non-Ashkenazi populations at rates
      comparable with that of Ashkenazim. The majority of Jewish 185delAG mutation
      carriers have a common allelic pattern, supporting the founder effect notion, but
      dating the mutation's origin to an earlier date than currently estimated.
      However, the different allelic pattern at the BRCA1 locus even in some Jewish
      mutation carriers, might suggest that the mutation arose independently.

PMID- 9536084
TI  - Missense mutation in a von Willebrand factor type A domain of the alpha 3(VI)
      collagen gene (COL6A3) in a family with Bethlem myopathy.
AB  - The Bethlem myopathy is a rare autosomal dominant proximal myopathy characterized
      by early childhood onset and joint contractures. Evidence for linkage and genetic
      heterogeneity has been established, with the majority of families linked to
      21q22.3 and one large family linked to 2q37, implicating the three type VI
      collagen subunit genes, COL6A1 (chromosome 21), COL6A2 (chromosome 21) and COL6A3
      (chromosome 2) as candidate genes. Mutations of the invariant glycine residues in
      the triple-helical domain-coding region of COL6A1 and COL6A2 have been reported
      previously in the chromosome 21-linked families. We report here the
      identification of a G-->A mutation in the N-terminal globular domain-coding
      region of COL6A3 in a large American pedigree (19 affected, 12 unaffected),
      leading to the substitution of glycine by glutamic acid in the N2 motif, which is
      homologous to the type A domains of the von Willebrand factor. This mutation
      segregated to all affected family members, to no unaffected family members, and
      was not identified in 338 unrelated Caucasian control chromosomes. Thus mutations
      in either the triple-helical domain or the globular domain of type VI collagen
      appear to cause Bethlem myopathy.

PMID- 9536085
TI  - A novel mammalian wnt gene, WNT8B, shows brain-restricted expression in early
      development, with sharply delimited expression boundaries in the developing
      forebrain.
AB  - Our current knowledge of mammalian forebrain development is meagre. The
      comparatively few relevant anatomical landmarks are, however, being supplemented
      by gene expression studies which are able to identify subsets of anatomical
      structures. We previously described cloning, subchromosomal localization and
      preliminary structural characterization of the human WNT8B gene, the first
      mammalian Wnt8b gene to be reported. Wnt genes encode intercellular signalling
      molecules which play a variety of critical roles in early development, including,
      in several cases, a presumed role in brain development. In the current report we
      present the full-length cDNA sequence and genomic organization of the human Wnt8b
      gene and report studies of expression of the Wnt8b gene in human and mouse
      embryos. The human and mouse expression patterns appeared identical and were
      restricted to the developing brain, with the great majority of expression being
      found in the developing forebrain. In the latter case expression was confined to
      the germinative neuroepithelium of three sharply delimited regions: the
      dorsomedial wall of the telencephalic ventricles (which includes the developing
      hippocampus), a discrete region of the dorsal thalamus and the mammillary and
      retromammillary regions of the posterior hypothalamus. Expression in the
      developing hippocampus may suggest a role for WNT8B in patterning of this region
      and subchromosomal localization of the human gene to 10q24 may suggest it as a
      candidate gene for partial epilepsy in families where the disease has been linked
      to markers in this region.

PMID- 9536086
TI  - mdx muscle pathology is independent of nNOS perturbation.
AB  - In skeletal muscle, neuronal nitric oxide synthase (nNOS) is anchored to the
      sarcolemma via the dystrophin-glycoprotein complex. When dystrophin is absent, as
      in Duchenne muscular dystrophy patients and in mdx mice, nNOS is mislocalized to
      the interior of the muscle fiber where it continues to produce nitric oxide. This
      has led to the hypothesis that free radical toxicity from mislocalized nNOS may
      contribute to mdx muscle pathology. To test this hypothesis directly, we
      generated mice devoid of both nNOS and dystrophin. Overall, the nNOS-dystrophin
      null mice maintained the dystrophic characteristics of mdx mice. We evaluated the
      mice for several features of the dystrophic phenotype, including membrane damage
      and muscle morphology. Removal of nNOS did not alter the extent of sarcolemma
      damage, which is a hallmark of the dystrophic phenotype. Furthermore, muscle from
      nNOS-dystrophin null mice maintain the histological features of mdx pathology.
      Our results demonstrate that relocalization of nNOS to the cytosol does not
      contribute significantly to mdx pathogenesis.

PMID- 9536087
TI  - Retrovirus-mediated enzymatic correction of Tay-Sachs defect in transduced and
      non-transduced cells.
AB  - Tay-Sachs disease is a severe neurodegenerative disorder due to mutations in the
      HEXA gene coding for the alpha-chain of the alpha-beta heterodimeric lysosomal
      enzyme beta-hexosaminidase A (HexA). Because no treatment is available for this
      disease, we have investigated the possibility of enzymatic correction of HexA
      deficient cells by HEXA gene transfer. Human HEXA cDNA was subcloned into a
      retroviral plasmid generating to G.HEXA vector. The best Psi-CRIP producer clone
      of G.HEXA retroviral particles was isolated, and murine HexA-deficient
      fibroblasts derived from hexa -/- mice were transduced with the G.HEXA vector.
      Transduced cells overexpressed the alpha-chain, resulting in the synthesis of
      interspecific HexA (human alpha-chain/murine beta-chain) and in a total
      correction of HexA deficiency. The alpha-chain was secreted in the culture medium
      and taken up by HexA-deficient cells via mannose-6-phosphate receptor binding,
      allowing for the restoration of intracellular HexA activity in non-transduced
      cells.

PMID- 9536088
TI  - Mutations of the flavin-containing monooxygenase gene (FMO3) cause
      trimethylaminuria, a defect in detoxication.
AB  - Individuals with the recessive condition trimethylaminuria exhibit variation in
      metabolic detoxication of xenobiotics by hepatic flavin-containing
      monooxygenases. We show here that mutations in the human flavin-containing
      monooxygenase isoform 3 gene ( FMO3 ) impair N -oxygenation of xenobiotics and
      are responsible for the trimethylaminuria phenotype. Three disease-causing
      mutations in nine Australian-born probands have been identified which share a
      particular polymorphic haplotype. Nonsense and missense mutations are associated
      with a severe phenotype and are also implicated in impaired metabolism of other
      nitrogen- and sulfur-containing substrates including biogenic amines, both
      clinically and when mutated proteins expressed from cDNA are studied in vitro .
      These findings illustrate the critical role played by human FMO3 in the
      metabolism of xenobiotic substrates and endogenous amines.

PMID- 9536089
TI  - Acyl-CoA:dihydroxyacetonephosphate acyltransferase: cloning of the human cDNA and
      resolution of the molecular basis in rhizomelic chondrodysplasia punctata type 2.
AB  - Rhizomelic chondrodysplasia punctata (RCDP) is a genetic disorder which is
      clinically characterized by rhizomelic shortening of the upper extremities,
      typical dysmorphic facial appearance, congenital contractures and severe growth
      and mental retardation. Patients with RCDP can be subdivided into three subgroups
      based on biochemical analyses and complementation studies. The largest subgroup
      contains patients with mutations in the PEX7 gene encoding the PTS2 receptor.
      This results in multiple peroxisomal abnormalities which includes a deficiency of
      acyl-CoA:dihydroxyacetonephosphate acyltransferase (DHAPAT), alkyl
      dihydroxyacetonephosphate synthase (alkyl-DHAP synthase), peroxisomal 3-ketoacyl
      CoA thiolase and phytanoyl-CoA hydroxylase, although there are differences in the
      extent of the deficiencies observed. Patients in the two other subgroups have
      been reported to be either deficient in the activity of DHAPAT (RCDP type 2) or
      alkyl-DHAP synthase (RCDP type 3) while no other abnormalities could be observed.
      To examine whether the gene encoding DHAPAT is mutated in patients with RCDP type
      2, we determined the N-terminal amino acid sequence of the enzyme isolated from
      human placenta. Using this sequence as a query, we identified a 2040 bp open
      reading frame (ORF) in the human database of expressed sequence tags. Expression
      of this ORF in the yeast Saccharomyces cerevisiae showed that we have identified
      the DHAPAT cDNA. The deduced amino acid sequence revealed no PTS2 consensus
      sequence. In contrast DHAPAT appears to contain a putative PTS1 at the extreme C
      terminus. All RCDP type 2 patients analyzed were found to contain mutations in
      their DHAPAT cDNA. This demonstrates that RCDP type 2 is the result of mutations
      in DHAPAT.

PMID- 9536090
TI  - Mutations in Emery-Dreifuss muscular dystrophy and their effects on emerin
      protein expression.
AB  - Seventeen families with Emery-Dreifuss muscular dystrophy (EDMD) have been
      studied both by DNA sequencing and by emerin protein expression. Fourteen had
      mutations in the X-linked emerin gene, while three showed evidence of autosomal
      inheritance. Twelve of the 14 emerin mutations caused early termination of
      translation. An in-frame deletion of six amino acids from the C-terminal
      transmembrane helix caused almost complete absence of emerin from muscle with no
      localization to the nuclear membrane, although mRNA levels were normal. This
      shows that mutant emerin proteins are unstable if they are unable to integrate
      into a membrane. A 22 bp deletion in the promoter region was expected to result
      in reduced emerin production, but normal amounts of emerin of normal size were
      found in leucocytes and lymphoblastoid cell lines. This shows that DNA analysis
      is necessary to exclude emerin mutations in suspected X-linked EDMD. Emerin
      levels in female carriers often deviated from the expected 50% and this was due,
      in at least two families, to skewed emerin mRNA expression from the normal and
      mutated alleles. In one family with a novel deletion of the last three exons of
      the emerin gene, a carrier had a cardiomyopathy and very low emerin levels (<5%
      of normal) due to skewed X-inactivation. In the three autosomal cases of EDMD,
      emerin was normal on western blots of blood cells, which suggests that autosomal
      EDMD is not caused by indirect reduction of emerin levels.

PMID- 9536091
TI  - Identification of a mutation in liver glycogen phosphorylase in glycogen storage
      disease type VI.
AB  - Glycogen storage disease type VI (GSD6) defines a group of disorders that cause
      hepatomegaly and hypoglycemia with reduced liver phosphorylase activity. The
      course of these disorders is generally mild, but definitive diagnosis requires
      invasive procedures. We analyzed a Mennonite kindred with an autosomal recessive
      form of GSD6 to determine the molecular defect and develop a non-invasive
      diagnostic test. Linkage analysis was performed using genetic markers flanking
      the liver glycogen phosphorylase gene ( PYGL ), which was suspected to be the
      cause of the disorder on biochemical grounds. Mennonite GSD6 was linked to the
      PYGL locus with a multipoint LOD score of 4.7. The PYGL gene was analyzed for
      mutations by sequencing genomic DNA. Sequencing of genomic DNA revealed a splice
      site abnormality of the intron 13 splice donor. Confirmation of the genomic
      mutation was performed by sequencing RT-PCR products, which showed heterogeneous
      PYGL mRNA lacking all or part of exon 13 in affected persons. This study is the
      first to demonstrate that a mutation in the PYGL gene can cause GSD6. This
      mutation is estimated to be present on 3% of Mennonite chromosomes and the
      disease affects 0.1% of that population. Determination of this mutation provides
      a basis for the development of a simple and non-invasive diagnostic test for the
      disease and the carrier state in this population and confirms biochemical data
      showing the importance of this gene in glucose homeostasis.

PMID- 9536092
TI  - Caveolin-3 in muscular dystrophy.
AB  - The dystrophin-glycoprotein complex (DGC) serves as a link between cytoplasmic
      actin, the membrane and the extracellular matrix of striated muscle. Genetic
      defects in genes encoding a subset of DGC proteins result in muscular dystrophy
      and a secondary decrease in other DGC proteins. Caveolae are dynamic structures
      that have been implicated in a number of functions including endocytosis,
      potocytosis and signal transduction. Caveolin (VIP-21) is thought to play a
      structural role in the formation of non-clathrin-coated vesicles in a number of
      different cell types. Caveolin-3, or M-caveolin, was identified as a muscle
      specific form of the caveolin family. We show that caveolin-3 co-purifies with
      dystrophin, and that a fraction of caveolin-3 is a dystrophin-associated protein.
      We isolated the gene for human caveolin-3 and mapped it to chromosome 3p25. We
      determined the genomic organization of human caveolin-3 and devised a screening
      strategy to look for mutations in caveolin-3 in patients with muscular dystrophy.
      Of 82 patients screened, two nucleotide changes were found that resulted in amino
      acid substitutions (G55S and C71W); these changes were not seen in a control
      population. The amino acid changes map to a functionally important domain in
      caveolin-3, suggesting that these are not benign polymorphisms and instead are
      disease-causing mutations.

PMID- 9536093
TI  - Genetic and molecular definition of complementation group D in MHC class II
      deficiency.
AB  - Four complementation groups, A, B, C and D, have been described among cell lines
      defective in the coordinate expression of MHC class II genes. These include cell
      lines established from patients affected with MHC class II deficiency and
      experimentally generated mutant cell lines. Group D, in contrast to the other
      groups, was for a long time represented only by the 6.1.6 mutant cell line. The
      gene responsible for the defect in this group, RFXAP , recently was cloned and
      found to be mutated in the 6.1.6 cell line and in three patients. Here we report
      fusion experiments in several new HLA class II-deficient patients, completing the
      classification of the majority of known patients into the four complementation
      groups. Patients from five unrelated families were classified in complementation
      group D, while nine others fall into complementation groups A and B. None of the
      patients defined a new complementation group. Full correction of MHC class II
      expression was obtained in cells from patients belonging to group D by
      transfection with the RFXAP cDNA. The RFXAP coding region was found to be mutated
      in all patients. Mutations were found to be recurrent since only three different
      mutations have been found in the eight unrelated families reported to date.

PMID- 9536094
TI  - High level of unequal meiotic crossovers at the origin of the 22q11. 2 and
      7q11.23 deletions.
AB  - Interstitial chromosomal deletions at 22q11.2 and 7q11.23 are detected in the
      vast majority of patients affected by CATCH 22 syndromes and the Williams-Beuren
      syndrome, respectively. In a group of 15 Williams-Beuren patients, we have shown
      previously that a large number of 7q11.23 deletions occur in association with an
      interchromosomal rearrangement, indicative of an unequal crossing-over event
      between the two homologous chromosomes 7. In this study, we show that a similar
      mechanism also underlies the formation of the 22q11.2 deletions associated with
      CATCH 22. In eight out of 10 families with a proband affected by CATCH 22, we
      were able to show that a meiotic recombination had occurred at the critical
      deleted region based on segregation analysis of grandparental haplotypes. The
      incidences of crossovers observed between the closest informative markers,
      proximal and distal to the deletion, were compared with the expected
      recombination frequencies between the markers. A significant number of
      recombination events occur at the breakpoint of deletions in CATCH 22 patients (P
      = 2.99x10(-7)). The segregation analysis of haplotypes in three-generation
      families was also performed on an extended number of Williams-Beuren cases (22
      cases in all). The statistically significant occurrence of meiotic crossovers (P
      = 4.45x10(-9)) further supports the previous findings. Thus, unequal meiotic
      crossover events appear to play a relevant role in the formation of the two
      interstitial deletions. The recurrence risk for healthy parents in cases where
      such meiotic recombinations can be demonstrated is probably negligible. Such a
      finding is in agreement with the predominantly sporadic occurrence of the 22q11.2
      and 7q11. 23 deletions. No parent-of-origin bias was observed in the two groups
      of patients with regard to the origin of the deletion and to the occurrence of
      inter- versus intrachromosomal rearrangements.

PMID- 9536095
TI  - Two distinct tumor suppressor loci within chromosome 11p15 implicated in breast
      cancer progression and metastasis.
AB  - Chromosome 11p15 has attracted considerable attention because of the biological
      importance of this region to human disease. Apart from being an important tumor
      suppressor locus showing loss of heterozygosity (LOH) in several adult and
      childhood cancers, 11p15 has been shown by linkage analysis to harbor the gene(s)
      for the Beckwith-Wiedemann syndrome. Furthermore, the clustering of known
      imprinted genes in the 11p15.5 region suggests that the target gene may also be
      imprinted. However, positional cloning efforts to identify the target genes have
      been complicated by the large size (approximately 10 Mb) and complexity of LOH at
      11p15. Here, we have analyzed 94 matched normal and breast tumor samples using 17
      polymorphic markers that map to 11p15.5-15.4. We have defined precisely the
      location of a breast tumor suppressor gene between the markers D11S1318 and
      D11S4088 (approximately 500 kb) within 11p15.5. LOH at this region occurred in
      approximately 35-45% of breast tumors analyzed. In addition, we have fine-mapped
      a second, critical region of LOH, that spans the markers D11S1338-D11S1323
      (approximately 336 kb) at 11p15.5-p15.4, that is lost in approximately 55-60% of
      breast tumors. There is a striking correlation between the loss of the two 11p
      loci and the clinical and histopathological features of breast tumors. LOH at
      region 1 correlated significantly (P = 0.016) with early events in malignancy and
      invasiveness. In contrast, the loss of the more proximal region 2, is highly
      predictive (P = 0.012) of aggressive metastatic disease. Thus, two distinct tumor
      suppressor loci on chromosome 11p15 may contribute to tumor progression and
      metastasis in breast cancer. The fine mapping of this intriguing chromosomal
      region should facilitate the cloning of the target genes and provide critical
      clues to understanding the mechanisms that contribute to the evolution of adult
      and childhood cancers.

PMID- 9536096
TI  - Chromosome 1 localization of a gene for autosomal dominant medullary cystic
      kidney disease.
AB  - There is a group of inherited cystic nephropathies that are characterized by
      juvenile onset recessive inheritance (familial juvenile nephronophthisis, FJN) or
      by adult onset dominant inheritance (medullary cystic disease, MCD) and share
      similar clinico-pathological presentation to the extent that they are usually
      grouped together under the term FJN/MCD complex. The main symptoms consist of
      renal cyst formation in the medulla or the corticomedullary junction and salt
      wasting. Although earlier reports had suggested that one single gene may be
      responsible for this pathology, recent reports have shown that the FJN complex
      itself comprises a genetically heterogeneous group. Here we are presenting two
      large Cypriot families that segregate autosomal dominant medullary cystic kidney
      disease (ADMCKD) with hyperuricemia and gout and with very late age of onset
      (mean 62.2 and 51.5 years). We performed DNA linkage mapping using highly
      polymorphic microsatellite markers and found linkage to marker locus D1S1595 at
      1q21 with a two-point lod score of 6.45 at Theta = 0.00. Analysis of haplotypes
      and of critical recombinants enabled confinement of the disease locus within an
      approximately 8 cM region between marker loci D1S498 and D1S2125. FISH mapping
      with a large P1 clone confirmed the physical localization within 1q21. The two
      families share the same disease haplotype, thus suggesting their relationship
      through a common ancestor and the possible existence of a single ADMCKD-causing
      mutation within these families. To our knowledge this is the first genetic locus
      identified to cause FJN/MCD pathology of the dominant adult type.

PMID- 9536097
TI  - Spinocerebellar ataxia type 7 (SCA7): a neurodegenerative disorder with neuronal
      intranuclear inclusions.
AB  - Autosomal dominant cerebellar ataxia with progressive macular degeneration is
      caused by a CAG/glutamine repeat expansion in the SCA7 gene/protein. Neuronal
      intranuclear inclusions were detected in the brain of an early onset SCA7 case
      with the 1C2 antibody directed against an expanded polyglutamine domain. Nuclear
      inclusions were most frequent in the inferior olivary complex, a site of severe
      neuronal loss in SCA7. They were also observed in other brain regions, including
      the cerebral cortex, not considered to be affected in the disease. Using confocal
      microscopy we showed that some inclusions were ubiquitinated, but to varying
      degrees, ranging from <1% in the cerebral cortex to 60% in the inferior olive. In
      addition, we also observed cytoplasmic staining using the 1C2 antibody,
      particularly in the supramarginal gyrus, the hippocampus, the thalamus, the
      lateral geniculate body and the pontine nuclei. These data confirm that the
      presence of intranuclear inclusions in neurons is a common characteristic of
      disorders caused by CAG/polyglutamine expansions, but unlike what has been
      reported for Huntington's disease, SCA1 and SCA3/MJD, in SCA7 the inclusions were
      not restricted to the sites of severe neuronal loss.

PMID- 9536098
TI  - Statistical features of human exons and their flanking regions.
AB  - To facilitate gene finding and for the investigation of human molecular genetics
      on a genome scale, we present a comprehensive survey on various statistical
      features of human exons. We first show that human exons with flanking genomic DNA
      sequences can be classified into 12 mutually exclusive categories. This
      classification could serve as a standard for future studies so that direct
      comparisons of results can be made. A database for eight categories (related to
      human genes in which coding regions are split by introns) was built from GenBank
      release 87.0 and analyzed by a number of methods to characterize statistical
      features of these sequences that may serve as controls or regulatory signals for
      gene expression. The statistical information compiled includes profiles of
      signals for transcription, splicing and translation, various compositional
      statistics and size distributions. Further analyses reveal novel correlations and
      constraints among different splicing features across an internal exon that are
      consistent with the Exon Definition model. This information is fundamental for a
      quantitative view of human gene organization, and should be invaluable for
      individual scientists to design human molecular genetics experiments.

PMID- 9536099
TI  - Analysis of the butyrylcholinesterase gene and nearby chromosome 3 markers in
      Alzheimer disease.
AB  - The K-variant of butyrylcholinesterase (BCHE-K) recently has been reported to be
      associated with Alzheimer disease (AD) in carriers of the epsilon4 allele of the
      apolipoprotein E (APOE) gene. We have re-examined the frequency of the BCHE-K
      allele in a large data set of both sporadic and familial cases of AD disease, and
      we have also examined the segregation of three genetic markers on chromosome 3
      near BCHE . Our data neither support an association of BCHE-K with sporadic or
      familial AD, nor do they suggest the existence of another gene nearby on
      chromosome 3 as a common cause of familial AD.

PMID- 9536100
TI  - No association between the K variant of the butyrylcholinesterase gene and
      pathologically confirmed Alzheimer's disease.
AB  - The polymorphic K variant of the butyrylcholinesterase ( BCHE-K ) gene recently
      has been demonstrated to have an elevated frequency in Alzheimer's disease (AD)
      patients carrying the epsilon4 allele of the apolipoprotein (APO E) gene when
      compared with a control population. We therefore genotyped a large series of
      pathologically confirmed AD patients and controls to confirm this association. We
      found no change in the frequency of this genetic variant, either in the AD group
      as a whole or in early- or late-onset patients when compared with age-matched
      controls. Stratification of these groups with reference to the APO E epsilon4
      allele also showed no difference between AD and control groups. To determine if a
      biological effect were present, we also looked at senile plaque and
      neurofibrillary tangle densities in the frontal, temporal, parietal and occipital
      cortices in AD patients either carrying or not carrying a copy of the K variant.
      We found no difference in plaque or tangle load between these two groups in
      either the total, late-onset or early-onset AD subjects. Stratification of the
      total AD group in terms of APO E epsilon4 allele possession, and further
      comparison of plaque and tangle load between carriers and non-carriers of BCHE-K
      still failed to disclose a relationship between BCHE-K and AD. We conclude that
      in the population studied here there is no association between BCHE-K and AD, or
      that if such a relationship exists it is precluded by another, as yet unknown
      factor.

PMID- 9536101
TI  - Changes in renal function with aging.
AB  - Despite losing 20%-25% of their original kidney volume, older individuals
      maintain body fluid hemostasis under most circumstances; however, their ability
      to withstand environmental, disease-related, or iatrogenic stresses becomes
      progressively narrowed. Glomerular filtration rates fall with each decade,
      accompanied by limitations on sodium conservation, potassium ion secretion, and
      acid excretion. Medications used by older patients are a common cause of
      hyperkalemia through a number of pathophysiologic mechanisms. In addition, water
      homeostasis frequently fails due to defects in thirst, urinary concentrating
      ability, and free water excretion, resulting in hypernatremia or hyponatremia in
      many sick older patients.

PMID- 9536102
TI  - Acute and chronic kidney disease.
AB  - The presentation of many renal diseases in older adults is remarkably similar to
      that in younger patients, although the symptoms and clinical findings are
      frequently attributed to diseases of aging. Since older patients often respond to
      treatment as well as younger patients do, they deserve a thorough investigation,
      including renal biopsy when indicated. It is important to base decisions
      regarding access to evaluation and treatment, quality of life, and initiation of
      termination of dialysis on strong moral and ethical grounds.

PMID- 9536104
TI  - End-stage renal disease and its management in older adults.
AB  - The older patient with renal disease presents the nephrologist with a formidable
      problem list: treatment of end-stage renal disease (ESRD) in these patients can
      be viewed as a continuum in the management of several diseases at one time. The
      older ESRD patient with complex medical problems is a challenge to the health
      care team, clearly requiring the cooperation of physician, nurse, dialysis
      technician, social worker, dietician, physical medicine specialist, and a host of
      other subspecialists. The outcomes, however, are gratifying, in that a
      satisfactory and enjoyable autumn of life is attainable for many.

PMID- 9536103
TI  - Renovascular disease in older adults.
AB  - Renovascular disease (RVD) as a cause of end-stage renal disease (ESRD) has been
      under-recognized until recently. As the population ages, the number of
      individuals with atherosclerotic RVD will increase, as will the number of
      patients with renovascular hypertension (RVH) and ESRD. The anatomic presence of
      atherosclerotic RVD as a threat to renal function has become a more pressing
      concern than that of hypertension secondary to RVD. This article reviews the
      causes, assessment, and treatment of RVD in older adults.

PMID- 9536105
TI  - Urinary tract infection in older adults.
AB  - Urinary tract infection is common among older adults, although most individuals
      are asymptomatic. The prevalence of bacteriuria varies significantly with living
      situation and functional status. Asymptomatic bacteriuria is a benign condition
      and is not an independent risk factor for mortality in older adults. Treatment of
      asymptomatic bacteriuria generally is not indicated, but symptomatic urinary
      tract infection of the lower or upper tract dictates antibiotic therapy.

PMID- 9536106
TI  - Urinary incontinence.
AB  - The involuntary loss of urine in a quantity or frequency sufficient to cause a
      social or hygienic problem is known as urinary incontinence. This common
      condition, affecting over 10 million adults, afflicts an estimated 30% of all
      older persons, as well as 50% to 70% of older residents in nursing homes. The
      clinical importance of urinary incontinence is due primarily to its adverse
      effects on psychologic health and social interactions; effects on physical
      health, such as skin maceration and recurrent urinary tract infections, are
      relatively minor. Because symptomatic improvement or cure is possible in many
      cases, health care providers should ask specific questions about symptoms of
      urinary incontinence and then provide appropriate evaluation and management of
      this common condition.

PMID- 9536107
TI  - Gynecologic problems in older women.
AB  - Regular gynecologic evaluation in older women is an integral part of medical
      care, just as it is for women of reproductive age. This should be emphasized
      since older women often neglect early symptoms of gynecologic diseases, some of
      which are potentially lethal. With this in mind, the health care provider must be
      cognizant of not only gynecologic problems that affect all women, but also those
      disease processes which are either specific to or more prevalent in an older
      population. This article emphasizes these aspects in caring for the older
      gynecologic patient.

PMID- 9536108
TI  - Benign prostatic hyperplasia in older men.
AB  - Urinary tract symptoms secondary to benign prostatic hyperplasia (BPH) may
      adversely affect quality of life in many older men. Evaluation of patients with
      BPH should be focused on excluding complicating factors such as urinary tract
      infection, renal dysfunction, and malignancy. Watchful waiting is an appropriate
      option for men in whom such complicating conditions have been excluded. For those
      men who elect to be treated, therapy using alpha blockers (terazosin, doxazosin)
      or 5-alpha reductase inhibitors (finasteride) should be offered initially.
      Surgical treatment is generally reserved for patients who do not have a
      sufficient response to medical therapy and those with absolute indications for
      intervention, such as complete retention, recurrent infection or hematuria, renal
      insufficiency, and bladder stones.

PMID- 9536109
TI  - Genitourinary cancers in older adults.
AB  - Prostate and bladder carcinoma are, in large part, diseases of older adults, and
      they are discussed in this context. Pathology, diagnosis, and staging are
      reviewed. Surgical and medical approaches to these malignancies, and the
      limitations of these approaches, are highlighted. Renal cell carcinoma, while a
      relatively rare neoplasm, remains a formidable challenge: approximately 50% of
      patients die within 5 years of diagnosis. Advances in molecular genetics and
      histopathologic classification, as well as surgical management and
      investigational therapies, are emphasized.

PMID- 9536110
TI  - Renal stone disease in older adults.
AB  - The pathophysiology of stone disorder in older adults, as compared to their
      younger counterparts, has not been thoroughly investigated. This article examines
      the differences in serum and urine chemistries between groups that are younger
      and older than 60 years of age. The principal finding is that stone formation
      occurs at lower urinary supersaturations in older patients, suggesting that other
      unexplored factors are significant contributors. The authors then review the
      possible effect of age on the morbidity of stone disease and the implications of
      stone disease for the development and management of osteoporosis.

PMID- 9536111
TI  - Sexual dysfunction in older adults.
AB  - Not only is sexual function an obvious requirement for the survival of the human
      race, but sex also is a major contributor to quality of life. During the recent
      past, there has been a dramatic increase in our understanding of sexual function
      and dysfunction in older men. There is, however, limited scientific information
      on the sexuality of older women. It is important that clinicians understand what
      is known about ways we can assist our older patients when they suffer from sexual
      dysfunction.

PMID- 9536112
TI  - Distinct T-cell subtypes induced with whole cell and acellular pertussis vaccines
      in children.
AB  - Recent clinical trials have demonstrated that new generation acellular pertussis
      vaccines can confer protection against whooping cough. However, the mechanism of
      protective immunity against Bordetella pertussis infection induced by vaccination
      remains to be defined. We have examined cellular immune responses in children
      immunized with a range of acellular and whole cell pertussis vaccines.
      Immunization of children with a potent whole-cell vaccine induced B. pertussis
      specific T cells that secreted interferon-gamma (IFN-gamma), but not interleukin
      5 (IL-5). In contrast, T cells from children immunized with acellular pertussis
      vaccines secreted IFN-gamma and/or IL-5 following stimulation with B. pertussis
      antigens in vitro. These observations suggest that protective immunity conferred
      by whole-cell vaccines, like natural immunity, is mediated by type 1 T cells,
      whereas the mechanism of immune protection generated with acellular vaccines may
      be more heterogeneous, involving T cells that secreted type 1 and type 2
      cytokines.

PMID- 9536113
TI  - Antigen direction of specific T-cell clones into gingival tissues.
AB  - This study was performed to investigate T-cell traffic to periodontal tissues
      during infection with a periodontal pathogen Actinobacillus actinomycetemcomitans
      (Aa). Rowett rat T-cell clones, A3 (CD4+ CD8-, alpha beta TCR+, NKRP-1-, specific
      to Aa) and G2 (CD4- CD8-, alpha beta TCR+, NKRP-1+, which reacts to Aa, Gram
      negative and -positive bacteria), both expressed the same prominent adhesion
      molecules (LFA-1, VLA-4) to the same extent. Binding of both T-cell clones to rat
      endothelial cells in vitro was blocked by antibody to VLA-4. Rowett rats were
      infected with Aa and infused with Aa-stimulated, isogenic T-clone lymphocytes
      that had been labelled in vitro with 125IUdR. Radioactivity associated with
      recovery of clone A3, but not G2, was significantly elevated in the gingivae of
      infected rats, suggesting migration to infected animals' gingival tissues.
      Migration of radioactive Aa-specific A3 clone cells traced by autoradiography
      reached a maximum at 24 hr (1.2% of total lymphocytes as radiolabelled cells in
      infected gingiva versus 0.6% in noninfected), indicating an apparent antigen
      directed retention in infected rats' gingival tissues. The G2 clone was not
      retained in the gingival tissues (0.20% of total lymphocytes as radiolabelled
      cells in infected gingiva versus 0.26% in non-infected). However, the possibility
      of A3 retention directed by inflammation or tissue-selective homing could not be
      excluded. In further experiments, other adoptively transferred T-clone
      lymphocytes [clones G23 (Th1) and F13 (Th2)] with specificity for the 29,000 MW
      outer membrane protein of Aa with the same prominent adhesion molecules could be
      recovered from rat gingivae previously challenged with this antigen. However,
      transferred T-clone lymphocytes [clone G26 (Th1)] with specificity for a
      different Aa antigen were not recovered. Therefore, the dynamics of cell entry
      into periodontal lesions vary for activated T lymphocytes with different
      antigenic specificities, indicating the significance of antigen in lymphocyte
      traffic to periodontal tissues.

PMID- 9536115
TI  - Differential activation requirements associated with stimulation of T cells via
      different epitopes of CD3.
AB  - A panel of monoclonal antibodies directed to different epitopes of porcine CD3
      were employed to investigate stimulation requirements of porcine T lymphocytes.
      It was found that epitope specificity was an important property of the anti-CD3
      antibodies that determined the requirements for T-cell proliferation. Thus, T
      cell proliferation induced by triggering different CD3 epitopes showed three
      different requirements: (a) proliferation induced by the most insensitive epitope
      required both epitope ligation and some unknown additional signal(s); (b)
      proliferation induced by the most common epitopes only required epitope ligation,
      either by monocytes or by immobilization; (c) proliferation induced by the most
      sensitive epitope required neither epitope ligation nor participation of antigen
      presenting cells (APC). These findings may help to explain the previous confusion
      over the requirements for T-cell activation through the CD3 pathway. Finally, the
      above conclusions apply only to alpha beta T cells, as porcine gamma delta T
      cells, either in bulk culture or isolated, did not proliferate in response to
      anti-CD3 stimulation. Therefore, the mechanism underlying gamma delta T-cell
      activation may be different from that of alpha beta T cells.

PMID- 9536114
TI  - Synovial fibroblasts as target cells for staphylococcal enterotoxin-induced T
      cell cytotoxicity.
AB  - Rheumatoid arthritis (RA) is a chronic autoimmune disease of unknown aetiology.
      Recently, superantigens have been implied in the pathogenesis of RA.
      Superantigens activate a large fraction of T cells leading to the production of
      cytokines and proliferation. In addition, superantigens direct cellular
      cytotoxicity towards major histocompatibility complex (MHC) class II-expressing
      cells. There is now increasing evidence that cytotoxic T cells may be involved in
      the pathogenesis of RA. In the inflamed synovia class II-positive synovial
      fibroblasts (SFC) are found. In the present study it was tested whether MHC class
      II-positive SFC serve as target cells for superantigen-induced cellular
      cytotoxicity. SFC were stimulated with interferon-gamma to express class II
      antigens, then they were cultivated in the presence of CD4-positive T cells with
      or without staphylococcal enterotoxins (SE). Cytotoxicity of T cells was measured
      as release of lactate dehydrogenase from SFC. Specific cytotoxicity was only
      found in the presence of class II-positive SFC depending on the dose of SE.
      Maximum lysis was seen after 20 hr. T-cell cytotoxicity was inhibited by
      antibodies to MHC class II antigens. The data suggest that class II-positive SFC
      not only function as accessory cells for SE-mediated T-cell proliferation and
      interleukin-2 production but may also be the targets of superantigen-mediated
      cellular cytotoxicity.

PMID- 9536116
TI  - Differential regulation of expression of the MHC class II molecules RT1.B and
      RT1.D on rat B lymphocytes: effects of interleukin-4, interleukin-13 and
      interferon-gamma.
AB  - Susceptibility to induction of both T helper 1- (Th1) and Th2-mediated
      autoimmunity is multifactorial and involves genetic linkage to the major
      histocompatibility complex (MHC) class II haplotype. Brown Norway (BN) rats
      exposed to mercuric chloride develop a Th2-dependent systemic autoimmunity,
      whereas Lewis rats, which are highly susceptible to Th1-mediated autoimmunity,
      develop immune suppression after mercuric chloride exposure. Exposure to mercuric
      chloride is known to enhance B-lymphocyte expression of the MHC class II molecule
      RT1.B, predominantly in BN rats. We demonstrate that, in contrast, expression of
      RT1.D was unmodified on these B cells, whereas both RT1.B and RT1.D were up
      regulated on epithelial cells. Regulation of B-cell MHC class II isotype
      expression was further studied in vitro, using BN rat lymph node (LN) cells.
      Interleukin-4 (IL-4) strongly enhanced B-cell expression of RT1.B (2.8-fold),
      whereas RT1.D expression was only slightly, although significantly, modified (1.2
      fold). B cells from Lewis rats showed a similar IL-4-induced enhancement of RT1.B
      expression (2.5-fold), whereas, in contrast, RT1.D expression was unmodified.
      Exposure of LN cells from BN rats to interferon-gamma induced a moderate increase
      of B-cell MHC class II expression, predominantly of RT1.B. Strong and rapid
      enhancement of B-cell RT1.D expression was observed after stimulation by phorbol
      12-myristate 13-acetate and ionomycin. Rat IL-13 did not modify B-cell MHC class
      II expression; however, it induced typical morphological changes in peritoneal
      macrophages. These experiments demonstrate isotype-specific and strain-dependent
      regulation of MHC class II expression on rat B lymphocytes, which may be of
      pathophysiological relevance for the strain-dependent susceptibility for Th1- or
      Th2-mediated autoimmunity.

PMID- 9536117
TI  - Neither interleukin-6 nor signalling via tumour necrosis factor receptor-1
      contribute to the adjuvant activity of Alum and Freund's adjuvant.
AB  - The potential contribution made by the inflammatory cytokines, interleukin-6 (IL
      6) and tumour necrosis factor-alpha (TNF-alpha) to the adjuvant activity of
      aluminium hydroxide gels (Alum) or Freund's complete adjuvant (FCA) was studied
      by comparing the immunological responses of IL-6- or TNF receptor 1- (p55; TNFR
      1) deficient mice with immunocompetent control mice. While both TNFR-1- and IL-6
      deficient mice primed with ovalbumin (OVA) prepared in either Alum or FCA
      produced similar IgG.1 responses in comparison to control mice, the pattern of T
      helper type 1- (Th1) dependent IgG2a production was significantly altered. In
      TNFR-1-deficient mice, IgG2a responses were greater than in control mice when
      FCA, but not when Alum, was used as an adjuvant. Correspondingly, spleen cells
      from FCA-inoculated TNFR-1-deficient mice restimulated with antigen in vitro
      produced higher Th1 cytokine (interferon-gamma; IFN-gamma) levels with no
      alteration in Th2 cytokine (IL-4; IL-5, IL-6 and IL-10) production in comparison
      with wild-type mice. Higher levels of IgG2a were also detected in IL-6-deficient
      mice compared with wild-type mice following inoculation with OVA prepared in
      either FCA or in Alum. Furthermore, analysis of cytokine production by spleen
      cells revealed that both Th1 and Th2 cytokine production was higher in IL-6
      deficient mice compared with control mice. As the majority of the effects of TNF
      alpha are mediated via TNFR-1, we conclude that this cytokine inhibits the
      adjuvant activities of FCA. Furthermore, the results also imply that
      immunopotentiating effects of FCA or Alum adjuvant are both inhibited by IL-6.

PMID- 9536118
TI  - Th1 cytokine mRNA expression dominates in the skin-draining lymph nodes of
      C57BL/6 mice following vaccination with irradiated Schistosoma mansoni cercariae,
      but is down-regulated upon challenge infection.
AB  - Vaccination of C57BL/6 mice with irradiated cercariae of Schistosoma mansoni
      results in the induction of high levels of immunity to subsequent infection. The
      events occurring in the lymph nodes draining the exposure site have been analysed
      ex vivo by reverse transcription-polymerase chain reaction (RT-PCR) and the
      timing of cytokine gene expression following exposure has been established. After
      vaccination, spatial separation of the T-helper type 1 (Th1) and Th2 responses
      was evident, with interferon-gamma (IFN-gamma), interleukin-2 (IL-2) and IL-12
      mRNA peaking earlier than mRNA for IL-4, IL-5 and IL-10. In contrast to the
      profiles observed post-vaccination, following challenge the IL-4 mRNA was
      predominant in the draining lymph nodes, with IFN-gamma message levels barely
      detectable above the naive level. These observations are confirmed by the
      analysis of IL-4 and IFN-gamma mRNA using competitive PCR. From these studies it
      is clear that irradiated cercariae are more able to promote a protective Th1
      response, with normal parasites eliciting higher IL-4 and IL-5 expression upon
      both primary and secondary stimulation.

PMID- 9536119
TI  - Nitric oxide produced in the lungs of mice immunized with the radiation
      attenuated schistosome vaccine is not the major agent causing challenge parasite
      elimination.
AB  - Mice vaccinated with radiation-attenuated cercariae of Schistosoma mansoni
      exhibit high levels of protection against a challenge with normal larvae. The
      immune effector mechanism, which operates against schistosomula in the lungs,
      requires CD4+ T cells capable of producing interferon-gamma (IFN-gamma). This
      cytokine can stimulate production of nitric oxide (NO), via its ability to up
      regulate inducible nitric oxide synthase (iNOS). We have therefore evaluated the
      potential role of NO in the effector mechanism operating in vaccinated mice.
      Evidence for the production of NO in the lungs of such animals was obtained from
      assays on antigen-stimulated airway cell cultures. Enhanced levels of NO,
      compared with those in cultures from control mice, were detected both after
      vaccination and after challenge; elevated levels of iNOS mRNA were also present
      in whole lung after challenge. However, administration of an iNOS inhibitor to
      vaccinated mice after percutaneous challenge did not significantly increase the
      worm burden. Furthermore, when mice with a disrupted iNOS gene were vaccinated
      they showed a highly significant level of protection. Although NO from activated
      macrophages can mediate cytotoxic killing of newly transformed schistosomula in
      vitro, we have demonstrated that the addition of erythrocytes to these larvicidal
      assays abolishes its effects. We interpret this to mean that once migrating
      schistosomula enter the bloodstream they will be protected against the cytotoxic
      actions of NO. Our data thus provide little evidence to implicate NO as a major
      component of the pulmonary effector response to S. mansoni in vaccinated mice.

PMID- 9536120
TI  - Predominant recognition of species-specific determinants of the GroES homologues
      from Mycobacterium leprae and M. tuberculosis.
AB  - The Mycobacterium leprae and M. tuberculosis 10,000 MW heat-shock protein
      homologues of GroES have previously been identified as major immunogens for human
      T cells. We used synthetic peptides to characterize the determinants recognized
      by murine T cells. The findings suggest that, despite 90% sequence identity
      between these two proteins, T cells recognize prominently the species-specific
      determinants localized within amino acid residues 21-40 and 49-72. Analysis of
      the molecular determinants of species-specificity for the M. leprae GroES
      sequence 25-40, using T-cell hybridomas and major histocompatibility complex
      (MHC)-binding assays, led to the identification of epitope cores and critical
      residues. Interestingly, closely overlapping epitope cores were found to be
      restricted by either H-2Ad (24-34) or H-2Ed (28-34). Furthermore, the site
      recognized by the M. leprae-specific monoclonal antibodies ML06 and ML10 was also
      localized in the overlapping sequences 25-31 and 25-29. In conclusion, we
      demonstrated that immunodominant species-specific T- and B-cell epitopes can be
      found in a mycobacterial heat-shock protein despite its highly conserved amino
      acid sequence. This finding suggests the feasibility of identifying a sufficient
      number of M. leprae-specific determinants for a composite T-cell immunodiagnostic
      reagent for tuberculoid leprosy.

PMID- 9536121
TI  - Effect of granulocyte-macrophage colony-stimulating factor on the number of
      leucocytes and course of Listeria monocytogenes infection in naive and
      leucocytopenic mice.
AB  - This study concerns the effect of recombinant murine granulocyte-macrophage
      colony-stimulating factor (GM-CSF) on the number of circulating leucocytes,
      activation of peritoneal macrophages and proliferation of Listeria monocytogenes
      in various organs of naive and leucocytopenic mice. Mice were rendered
      leucocytopenic by sublethal total body irradiation or cyclophosphamide treatment.
      GM-CSF treatment enhanced the number of granulocytes and monocytes in peripheral
      blood during L. monocytogenes infection in naive mice, but not in irradiated or
      cyclophosphamide-treated mice. In naive mice, irradiated and cyclophosphamide
      treated mice, GM-CSF did not affect the course of L. monocytogenes infection in
      thigh muscle, spleen and liver. However, GM-CSF treatment significantly increased
      the number of macrophages in the peritoneal cavity of naive mice during
      infection; these macrophages were more enlarged and showed a higher frequency of
      binucleated and multinucleated cells relative to non-GM-CSF-treated mice.
      Together, these results demonstrated that GM-CSF increased the number of
      circulating granulocytes and monocytes, and the number of peritoneal macrophages
      during infection with L. monocytogenes in naive mice, but did not affect the
      course of the infection in thigh muscle, spleen or liver of these mice. In
      leucocytopenic mice, however, GM-CSF did not affect the number of circulating
      phagocytes, which explains that this factor had no effect on the proliferation of
      the bacteria in the various organs.

PMID- 9536122
TI  - The dual role of interferon-gamma in experimental Staphylococcus aureus
      septicaemia versus arthritis.
AB  - To evaluate the role of interferon-gamma (IFN-gamma) in Staphylococcus aureus
      infection, we investigated the effects of supplementation with and neutralization
      of IFN-gamma during septicaemia and arthritis in a murine model. In vivo
      administration of IFN-gamma both before and after bacterial inoculation
      significantly decreased mortality on one hand but enhanced the development of
      arthritis on the other. Treatment of mice with anti-IFN-gamma monoclonal
      antibodies (mAb) before and after bacterial inoculation did not significantly
      influence the survival rate but decreased the frequency and severity of
      arthritis. The beneficial effect of supplementation with IFN-gamma on septicaemia
      was correlated to the increased phagocytosis and bacterial clearance from liver
      and kidneys. The down-regulation of the development of arthritis by anti-IFN
      gamma mAb was accompanied by the decreased serum tumour necrosis factor-alpha,
      interleukin-6 and interleukin-1 beta levels. These results demonstrate a
      significant role for IFN-gamma in simultaneous protection against septicaemia but
      promotion for the development of septic arthritis.

PMID- 9536124
TI  - Peroxynitrite-mediated DNA strand breakage activates poly (ADP-ribose) synthetase
      and causes cellular energy depletion in carrageenan-induced pleurisy.
AB  - The aim of the present study was to investigate the role of poly (ADP-ribose)
      synthetase in acute local inflammation (carrageenan-induced pleurisy), where
      oxyradicals, nitric oxide and peroxynitrite are known to play a crucial role in
      the inflammatory process. DNA single-strand breakage and activation of the
      nuclear enzyme poly (ADP-ribose) synthetase (PARS) triggers an energy-consuming,
      inefficient repair cycle, which contributes to peroxynitrite-induced cellular
      injury. Here we investigated whether peroxynitrite production and PARS activation
      are involved in cytotoxicity in macrophages collected from rats subjected to
      carrageenan-induced pleurisy. Macrophages harvested from the pleural cavity
      exhibited a significant production of peroxynitrite, as measured by the oxidation
      of the fluorescent dye dihydrorhodamine 123, and by nitrotyrosine Western
      blotting at 4 hr after carrageenan injection. Furthermore, carrageenan-induced
      pleurisy caused a suppression of macrophage mitochondrial respiration, DNA strand
      breakage, activation of PARS and reduction of NAD+ cellular levels. In vivo
      treatment with 3-aminobenzamide (10 mg/kg intraperitoneally, 1 hr after
      carrageenin injection) significantly inhibited the decrease in mitochondrial
      respiration and the activation of PARS and partially restored the cellular level
      of NAD+. In a separate group of experiments, in vivo pretreatment with NG-nitro-L
      arginine methyl ester, a non-selective inhibitor of nitric oxide (NO) synthesis
      (10 mg/kg intraperitoneally, 15 min before carrageenan administration), reduced
      peroxynitrite formation and prevented the appearance of DNA damage, the decrease
      in mitochondrial respiration and the loss of cellular levels of NAD+. Our study
      suggests that formation of peroxynitrite and subsequent activation of PARS may
      alter macrophage function in inflammatory processes and inhibition of NO and PARS
      may be a novel pharmacological approach to prevent cell injury in inflammation.

PMID- 9536123
TI  - Group B streptococci persist inside macrophages.
AB  - Group B streptococci (GBS) are an important cause of neonatal sepsis, pneumonia
      and meningitis. In the early phase of infection, macrophages and
      polymorphonuclear cells (PMN) are the first immune cells that interact with GBS.
      In this in vitro study, to gain insight into GBS-macrophage interaction in the
      absence of type-specific antibodies, we examined the features of GBS survival in
      thioglycollate-elicited murine peritoneal macrophages and the effect of GBS on
      the protein kinase C (PKC)-dependent transduction pathway. Our results
      demonstrate that type Ia GBS, strain 090 (GBS-Ia) and type III GBS strain COH
      31r/s (GBS-III), after in vitro phagocytosis survive and persist intracellularly
      in macrophages for up to 24 and 48 hr, respectively. However, macrophage
      activation by interferon-gamma (IFN-gamma) and lipopolysaccharide from
      Escherichia coli (LPS) caused a significant reduction in the time of
      intracellular persistence. Macrophage activation by IFN-gamma and LPS seems to be
      a multifactorial event involving multiple intracellular signal pathways also
      including PKC. Since PKC is one of the components in the signal network leading
      to macrophage activation and an important target for several intracellular micro
      organisms, we wondered whether PKC could have a role in intracellular GBS
      survival. Both PKC depletion by treatment with phorbol 12-myristate 13-acetate
      (PMA) for 18 hr and PKC inhibition by Calphostin C rendered macrophages more
      permissive for the intracellular GBS survival. Furthermore, GBS-infected
      macrophages were unable to respond to PMA and LPS, activators of PKC, by inducing
      antimicrobial activity. The ability of GBS to impair PKC-dependent cell
      signalling was also demonstrated by the reduced c-fos gene expression in GBS
      infected macrophages with respect to control macrophages, after LPS stimulation.
      In conclusion, our results indicate that GBS survive in macrophages and
      impairment of PKC signal transduction contributes to their intracellular
      survival.

PMID- 9536125
TI  - Nitric oxide-mediated cytotoxic effects of alveolar macrophages on transformed
      lung epithelial cells are independent of the beta 2 integrin-mediated
      intercellular adhesion.
AB  - It is known that murine macrophages produce nitric oxide (NO) when stimulated
      with lipopolysaccharide (LPS) or interferon-gamma (IFN-gamma), and NO mediates
      the tumoricidal activity of activated macrophages. The present study was designed
      to investigate whether the intercellular adhesion is necessary for activated rat
      alveolar macrophages to exert the full cytotoxic effects. Rat alveolar
      macrophages produced NO dose dependently in response to either LPS or IFN-gamma,
      and caused DNA fragmentation in rat type II pneumocytes transformed with SV40
      (SV40T2). Chemically produced NO also caused the DNA fragmentation and viability
      loss in SV40T2, and both of them were inhibited by a NO radical scavenger. The
      cytotoxicity of activated macrophages was reduced by NG-monomethyl-L-arginine, a
      competitive nitric synthase inhibitor, and neither superoxide dismutase nor
      catalase modulated the cytotoxicity. Although alveolar macrophages stimulated
      with either LPS or IFN-gamma caused DNA fragmentation of SV40T2, only LPS
      increased the intercellular adherence between macrophages and SV40T2. The
      intercellular adhesion was reduced by both anti-CD18 and anti-CD11a. However,
      those antibodies did not affect the cytotoxicity of LPS-stimulated macrophages.
      These results clearly indicate that NO-mediated cytotoxicity is caused
      predominantly by diffusion of NO, and the beta 2 integrin-mediated intercellular
      adhesion does not play an important role, if any, in activated macrophage
      mediated cytotoxic effects on SV40T2.

PMID- 9536126
TI  - Different endothelins stimulate cytokine production by peritoneal macrophages and
      microglial cell line.
AB  - Endothelins (ETs), potent vasoconstricting peptides, are produced by macrophages
      upon stimulation and may participate in the amplification or regulation of the
      inflammatory response. However, it is not clear whether ETs can act in an
      autocrine manner on macrophages and which role they play in relationship with
      other cytokines. To address these issues, we studied the effects of ETs on the
      production of inflammatory cytokines by mouse peritoneal macrophages or by a
      retrovirus-transformed microglial cell line. Here, we report that ET-2, but not
      ET-1 or ET-3, is able to stimulate the production of interleukin-1 (IL-1) and
      interleukin-6 (IL-6) by peptone-elicited mouse macrophages (pMO). In contrast, ET
      3 and ET-1, but not ET-2, are active on microglial cells. No tumour necrosis
      factor-alpha (TNF-alpha) or nitric oxide (NO) were detected in the supernatants
      of ET-stimulated cultures. The activity of ET-2 on pMO was time and dose
      dependent and was inhibited by the addition of ETA and ETB receptor antagonists,
      BQ123 and IRL1038, respectively. In addition, when pMO were stimulated by
      interferon-gamma (IFN-gamma) in the presence of ET-2, a significant inhibition of
      IL-6 and IL-1 production was observed compared with the effects of the same doses
      of IFN-gamma or ET-2 used separately. The inhibition was specifically due to the
      activity of ET-2, since it was reversed by the addition of BQ123 or IRL1038.
      Similar results were seen when the content of NO in the supernatants of pMO
      stimulated by IFN-gamma plus ET-2 was evaluated. These results suggest that ETs
      may possess both a pro-inflammatory action on macrophages from different tissues
      and a regulatory activity on IFN-gamma.

PMID- 9536127
TI  - Cathepsin G enhances human natural killer cytotoxicity.
AB  - Cathepsin G is a serine protease located in the azurophil granules of
      neutrophils. In this study, we investigated the effect of cathepsin G on the
      functions of human natural killer (NK) cells in vitro. Cathepsin G enhanced NK
      cytotoxicity rapidly in a dose-dependent fashion. The ability to augment NK
      cytotoxicity was markedly reduced in the presence of the inhibitor,
      phenylmethanesulphonyl fluoride (PMSF) or chymostatin, demonstrating that the
      proteolytic activity of cathepsin G is essential for the induction of NK
      cytotoxicity. Granulocyte exocytosis is required for NK cell-dependent target
      killing. Cathepsin G induced the release of the granule enzyme, N-acetyl-beta-D
      glucosaminidase, from human NK cells. Moreover, an increase in the cytosolic-free
      Ca2+ concentration was observed in NK cells after stimulation with cathepsin G.
      When human granulocytes were stimulated with cytochalasin B and N-formyl
      methionyl-leucyl-phenylalanine (fMLP), cathepsin G was released. The cathepsin G
      released from granulocytes also caused enhancement of NK cytotoxicity. In the
      presence of serine protease inhibitor the supernatant including cathepsin G
      obtained from stimulated granulocytes did not enhance NK cytotoxicity, but the
      stimulated granulocytes did. Highly purified human NK cells treated with
      cathepsin G enhanced NK cytotoxicity, but NK-depleted lymphocytes did not,
      demonstrating that cathepsin G regulates NK cytotoxicity independently of other
      factors. We have shown recently that human cathepsin G binds to human NK cells.
      These combined data indicate that cathepsin G released from granulocytes binds to
      NK cells and augments NK cytotoxicity through its protease activity.

PMID- 9536128
TI  - Monoclonal antibody anti-NC-2 identifies a second receptor on cells mediating
      natural cytotoxicity in mice.
AB  - We have previously reported the identification by the murine monoclonal antibody
      (mAb) 1C4 of the first leucocyte receptor which is involved in natural
      cytotoxicity (NC) against WEHI-164; the NC-1.1 receptor. We report herein the
      identification and characterization of a second leucocyte receptor which is
      involved in NC, NC-2 (MW 50,000), identified by a rat anti-mouse mAb D9
      (immunoglobulin G2a; IgG2a). Flow cytometric analysis showed that NC-2 was
      expressed on < 6% of splenic leucocytes of different inbred mouse strains and 96%
      of the cells of a mast-cell line which has high NC activity. In vitro treatment
      of splenic leucocytes with the D9 mAb blocked effector cell-WEHI-164 target cell
      conjugation and NC by approximately 50% without affecting natural killing (NK).
      Western blot analysis of affinity purified NC-2 and NC-1.1 using the D9 and 1C4
      mAbs showed specific reactivity of the proteins with D9 and 1C4, respectively.
      Pretreatment of splenic leucocytes with both mAbs blocked NC 84%, a result which
      almost doubled that caused by either mAb alone. Flow cytometric screening of 16
      different mouse cell lines showed that 19% of the cell lines expressed both
      receptors, 6% expressed only NC-2, 44% expressed mainly or only NC-1.1 and the
      remaining cells expressed neither receptor. These data indicate that D9
      identifies a xeno-antigen, NC-2, which is expressed on cells mediating NC and not
      NK, and that it is not the previously described NC-1.1 allo-antigen. We conclude
      that NC-2 is likely to be one of a number of receptor molecules on cells
      mediating NC against tumour cells.

PMID- 9536130
TI  - More than an end of term report.

PMID- 9536129
TI  - Human monoclonal antibodies encoded by the V4-34 gene segment show cold
      agglutinin activity and variable multireactivity which correlates with the
      predicted charge of the heavy-chain variable region.
AB  - We have characterized the reactivities of a panel of V4-34-encoded human IgM
      monoclonal antibodies (mAb) which bind the erythrocyte Rh D antigen, derived from
      an immunized individual. These were compared with the specificities of V4-34
      encoded autoantibodies with I/i reactivity produced from patients with cold
      agglutinin disease (CAD), and other V4-34-encoded autoantibodies. The antibodies
      were evaluated for cold agglutinin activity using haemagglutination tests,
      immunofluorescence microscopy for reactivity with tissue components, and in solid
      phase radiobinding assays with purified antigens. We found that (i) cold
      agglutinin activity was a property of all the V4-34-encoded mAb (ii) the cold
      agglutinins from CAD patients were generally monospecific for I/i whereas most of
      the anti-D and the other V4-34-encoded mAb displayed multireactive properties,
      frequently binding to strongly acidic antigens (iii) computation of the net
      charge of the heavy-chain V regions showed that the multireactive mAb were
      generally more positively charged than the monospecific cold agglutinins, which
      could contribute to their multireactive phenotype. The involvement of charge
      interactions was further indicated by the effects of pH and ionic strength on the
      immunofluorescence staining patterns.

PMID- 9536131
TI  - Controlling the introduction of new and emerging medical technologies: can we
      meet the challenge?

PMID- 9536132
TI  - Prevalence and mechanisms of gastro-oesophageal reflux in adult cystic fibrosis
      patients.
AB  - Gastro-oesophageal reflux (GOR) occurs frequently in children with cystic
      fibrosis (CF) but has not been studied in adult CF. We surveyed such symptoms by
      structured questionnaire in 50 adult CF patients (mean age 26 years, range 16-50;
      24 male) and performed oesophageal manometry and 24-hour pH recording in 10 who
      had reflux symptoms (mean age 28 years, range 21-35; 8 men). 47 patients (94%)
      had upper gastrointestinal symptoms: 40 (80%) heartburn (27 worse when supine);
      26 (52%) regurgitation; and 28 (56%) dyspepsia. At oesophageal manometry, lower
      oesophageal sphincter barrier pressure (LOSBP) was subnormal in 6 of the 10
      patients and 3 had uncoordinated peristalsis in the mid oesophagus. 8 patients
      had raised DeMeester scores, indicating significant GOR. Those patients with a
      LOSBP < 5mm Hg had a higher DeMeester score (mean 81.0, range 47.9-128.8) than
      the patients with a normal LOSBP (26.9, 8.7-56.5; p < 0.002). These results show
      that adult CF patients have high rates of GOR symptoms, diminished LOSBP, and
      acid reflux.

PMID- 9536133
TI  - Tracheal microaspiration in adult cystic fibrosis.
AB  - Gastro-oesophageal reflux (GOR) has been implicated in the aetiology of lung
      disease. Cystic fibrosis (CF) patients have a high incidence of GOR symptoms with
      demonstrable episodes of oesophageal acidification. We studied 24-hour ambulatory
      tracheal and oesophageal pH in 11 CF patients with GOR symptoms to identify any
      episodes of tracheal acidification and define their temporal relation to
      oesophageal reflux and respiratory symptoms. 8 patients had evidence of
      significant GOR (DeMeester score mean 58; range 17-107) and in 6 it was gross
      (DeMeester score > 30). 4 patients had tracheal acidification (defined as
      tracheal pH < 5.5): all had greatly raised DeMeester scores. Two patterns of
      lowered tracheal pH were seen: a gradual drift downwards of tracheal pH to < 5.5
      which recovered slowly, and an acute fall in tracheal pH to < 5.5 with rapid
      recovery. Only one patient had a fall in peak expiratory flow in conjunction with
      a decline in tracheal pH, and no association was found between the presence of
      tracheal microaspiration and pulmonary function. We conclude that tracheal
      acidification occurs in adult CF patients with GOR.

PMID- 9536135
TI  - Internet discussion lists.

PMID- 9536134
TI  - Psychiatric disorders after transurethral resection of the prostate.
AB  - Three men in their 70s had long-term changes in mood and personality dating from
      immediately after transurethral prostatectomy. Focal abnormalities in the brain
      were not detected. The possibility of psychiatric as well as cardiovascular
      sequelae from this operation deserves investigation.

PMID- 9536136
TI  - Problem feet in children.

PMID- 9536137
TI  - Organization of trauma care in the UK.

PMID- 9536138
TI  - Early management of the severely injured patient.

PMID- 9536139
TI  - Rehabilitation after sensory neuronopathy syndrome.

PMID- 9536140
TI  - Breast cancer after radiotherapy for Hodgkin's disease.

PMID- 9536141
TI  - Diabetic ketoacidosis in non-insulin-dependent diabetes mellitus.

PMID- 9536142
TI  - Soft-tissue thumb reconstruction.

PMID- 9536143
TI  - Hypopituitarism after adult acute lymphoblastic leukaemia.

PMID- 9536144
TI  - Iatrogenic complications of depot antipsychotics given to unfamiliar patients.

PMID- 9536145
TI  - Oral self-mutilation masquerading as malignancy.

PMID- 9536146
TI  - Eating disorders, nursing and the Allitt report.

PMID- 9536147
TI  - The prostate in Cleveland, Ohio.

PMID- 9536148
TI  - A thirteenth-century ophthalmologist, Benvenutus Grassus: his treatise and its
      survival.

PMID- 9536149
TI  - Phytophotodermatitis mimicking child abuse.

PMID- 9536150
TI  - Psychiatric stigmatization.

PMID- 9536151
TI  - Laboratory instrumentation in clinical biochemistry.

PMID- 9536152
TI  - Peanut allergy.

PMID- 9536153
TI  - Quinine for leg cramp: time to call a halt?

PMID- 9536154
TI  - If one green bottle should accidently fall.

PMID- 9536155
TI  - Tropical ulcers and diphtheria.

PMID- 9536157
TI  - Acute effects of ozone on pulmonary function of cyclists receiving antioxidant
      supplements.
AB  - OBJECTIVES: To identify whether acute lung function effects of ozone can be
      modulated by antioxidant vitamin supplementation. METHODS: Amateur cyclists (n =
      26) were studied in the summer of 1994 in The Netherlands. Repeated lung function
      measurements were performed with a rolling seal spirometer after training
      sessions or competitive races on four to 14 occasions. The cyclists were assigned
      to two study groups. The supplementation group (n = 12) received antioxidant
      supplements (15 mg beta-carotene, 75 mg vitamin E, and 650 mg vitamin C) once a
      day for three months. The control group did not receive supplementation. For each
      subject, lung function after exercise was regressed on the previous eight hour
      mean ozone concentration. The individual regression coefficients were pooled for
      each study group and weighted with the inverse of the variance. RESULTS: The
      eight hour mean ozone concentration was 101 micrograms/m3 (30 to 205
      micrograms/m3). For the supplementation group, there was no effect of ozone on
      FVC, FEV1, peak expiratory flow (PEF), and maximal mid-expiratory flow (MMEF).
      For the control group the mean coefficients were negative, except for MMEF. The
      difference between the groups was 2.08 (95% confidence interval (95% CI) 1.31 to
      2.85) ml/microgram/m3 for FVC, 1.66 (95% CI 0.62 to 2.70) for FEV1, 6.83 (95% CI
      3.17 to 10.49) for PEF, and 0.42 (95% CI -1.38 to 2.22) for MMEF. CONCLUSION: The
      results suggest that antioxidant vitamin supplementation protects against acute
      effects of ozone on lung function in heavily exercising amateur cyclists.

PMID- 9536156
TI  - Cancer risk in the rubber industry: a review of the recent epidemiological
      evidence.
AB  - OBJECTIVES: To examine the recent epidemiological evidence on cancer risk among
      workers in the rubber industry. METHODS: Epidemiological studies published after
      the last detailed review by the International Agency for Research on Cancer
      (IARC) in 1982 were reviewed. 12 cohort studies in nine countries that examined
      distinct populations of workers in the rubber industry, seven industry based
      nested case-control studies, 48 community based case-control studies in 16
      countries, and 23 studies based on administrative data that reported risks for
      employment in the rubber industry were identified. RESULTS: Excess risks of
      bladder cancer, lung cancer, and leukaemia were found in most studies, with risks
      above 1.5 in about half of the studies. A moderate excess risk for laryngeal
      cancer was consistent across studies. Excess risks were found in a few studies
      for cancers of the oesophagus, stomach, colon, liver, pancreas, skin, prostate,
      kidney, brain, and thyroid, and for malignant lymphoma and multiple myeloma, but
      overall results were not consistent for these neoplasms. CONCLUSIONS: Magnitude
      of the observed risks varied considerably between studies, but overall the
      findings indicate the presence of a widespread moderate increased cancer risk
      among rubber workers. The most consistent results were for bladder, laryngeal,
      and lung cancer and for leukaemia. Excess risks were also found for other
      neoplasms but an evaluation of the consistency of the findings is difficult
      because of the possible selective reporting of results. Recent studies do not
      provide information associating specific exposures with cancer risk. The
      preventive measures taken in the rubber industry in recent years may decrease
      risks, but this has not been documented yet in epidemiological studies.

PMID- 9536158
TI  - Birthweight of term infants and maternal occupation in a prospective cohort of
      pregnant women. The ALSPAC Study Team.
AB  - OBJECTIVE: To study the relation between birthweight of term infants and maternal
      occupation. METHODS: Information on job titles since the age of 16, and
      sociodemographic and other lifestyle factors were obtained by means of
      questionnaires as part of the Avon longitudinal study of pregnancy and childhood
      (ALSPAC), from a cohort of 14,000 pregnant women. The British 1990 standard
      occupational classification was used to code jobs within nine major job groups.
      RESULTS: For 9282 women who delivered term infants and reported a job for the
      relevant period, there was a significant difference in mean birthweight among the
      nine major job groups. A 148 g difference was found between the mean birthweight
      of infants born to women with professional occupations and those with plant and
      machine operative jobs. Multiple regression analysis adjusted for sex of infant,
      parity, maternal height, smoking, caffeine consumption, and race. After
      adjustment the maternal job was no longer significantly associated with
      birthweight. CONCLUSION: Despite the absence of a significant association between
      birthweight and job after adjustment, there were several findings which agreed
      with publications on maternal occupation and pregnancy outcome. The major job
      groups with the lowest birthweights included the following jobs; metal forming or
      welding, electric or electronic work, jobs in the textile trade, and assembling
      and working with equipment (mobile and stationary). The lack of an association
      may indicate that the study was of insufficient power to detect a small
      difference; it may indicate the presence of confounding variables that were not
      adjusted for or it may indicate that no association exists.

PMID- 9536159
TI  - Time to pregnancy among the wives of men exposed to organic solvents.
AB  - OBJECTIVES: To assess whether paternal exposure to organic solvents is associated
      with decreased fertility. METHODS: A retrospective time to pregnancy study was
      conducted among men biologically monitored for organic solvents. The workers were
      classified into exposure categories on the basis of work description and the use
      of solvents as reported in the questionnaires, and on biological exposure
      measurements. The relative fecundability density ratios (FDR--an analogue of
      incidence density ratio of clinically recognised pregnancies) were calculated
      with discrete proportional hazards regression. RESULTS: After three mailings 316
      (72.1%) wives of the monitored men participated. The final study population
      consisted of 282 couples who did not use contraception at the beginning of
      pregnancy. The FDRs, adjusted for potential confounders, were 0.80 (95%
      confidence interval (95% CI) 0.57 to 1.11) and 0.74 (95% CI 0.51 to 1.06) for
      high or frequent and low or intermediate exposure, respectively. High or frequent
      and low or intermediate exposure were related to decreased fecundability among
      primigravida (FDRs 0.36; 95% CI 0.19 to 0.66 and 0.53; 95% CI 0.27 to 1.04) but
      not among couples with at least one previous pregnancy (FDRs 0.96; 95% CI 0.62 to
      1.49 and 0.77; 95% CI 0.47 to 1.24). CONCLUSIONS: The findings of the study
      provide limited support for the hypothesis that paternal exposure to organic
      solvents might be associated with decreased fertility. Further studies with
      careful design are warranted.

PMID- 9536160
TI  - Association of petrochemical exposure with spontaneous abortion.
AB  - OBJECTIVES: To assess the association between petrochemical exposure and
      spontaneous abortion, a retrospective epidemiological study in a large
      petrochemical complex in Beijing, China was conducted. METHODS: Plant employment
      records identified 3105 women who were married, were 20-44 years of age, and had
      never smoked. Of those, 3070 women (98.8%) reported at least one pregnancy. From
      this group, 2853 (93%) of the women participated in the study. According to their
      plant employment record, about 57% of these women workers reported occupational
      exposure to petrochemicals during the first trimester of their pregnancy. Trained
      interviewers administered a standardised questionnaire to this group of women and
      their husbands, collecting information on reproductive history, pregnancy
      outcomes, employment history, occupational exposure, smoking habits, alcohol
      consumption, indoor air pollution, and demographic variables. The results from
      the womens' first pregnancies were analysed. RESULTS: There was a significantly
      increased risk of spontaneous abortion for women working in all of the production
      plants with frequent exposure to petrochemicals (8.8%; range of 5.8%-9.8%)
      compared with those working in nonchemical plants (2.2%; range of 0.0%-7.1%).
      Also, when a comparison was made between exposed and non-exposed groups within
      each plant, exposure to petrochemicals was consistently associated with an
      increased risk of spontaneous abortion. The overall odds ratio (OR) was 2.7 (95%
      confidence interval (95% CI) 1.8 to 3.9) after adjusting for potential
      confounders. When the analysis was performed with the exposure information
      obtained from the women' interview responses for (self reported) exposures, the
      estimated OR for spontaneous abortions was 2.9 (95% CI 2.0 to 4.0). The analysis
      was repeated by excluding those 452 women who provided inconsistent reports
      between recalled exposure and work history, and a comparable risk of spontaneous
      abortion (OR 2.9; 95% CI 2.0 to 4.4) was found. In analyses for exposure to
      specific chemicals, an increased risk of spontaneous abortion was found with
      exposure to most chemicals, and the results for benzene (OR 2.5; 95% CI 1.7 to
      3.7), gasoline (OR 1.8; 95% CI 1.1 to 2.9), and hydrogen sulphide (OR 2.3; 95% CI
      1.2 to 4.4) were significant. CONCLUSION: An increased risk of spontaneous
      abortion was found associated with the exposure to petrochemicals, including
      benzene, gasoline, and hydrogen sulphide.

PMID- 9536161
TI  - Assessment of exposure to solvents among hairdressers: reliability of a
      classification scheme and questionnaire.
AB  - OBJECTIVES: To assess the reliability of a classification scheme and interview
      questions to be used for retrospective expose assessment in a study on
      reproductive disorders among hairdressers. Based on the presence of an air
      cleaning device (yes or no) and setting waves (yes or no), this scheme divides
      hairdressers into groups with potentially high and low exposure to solvents. The
      reliability of this and other schemes was assessed. Also; the reliability of self
      reports on other job characteristics was evaluated. METHODS: The monitored
      hairdressers were interviewed one or two years after measurements were performed.
      Based on the interview information, hairdressers were classified into exposure
      groups according to the original and other classification schemes. Measured
      ethanol concentrations were compared between the classified exposure groups.
      Furthermore, the interview answers were compared with the registered information
      one to two years ago. RESULTS: Using self reports, the original scheme resulted
      in mean ethanol concentrations (used as indicator variable) of 11.8 and 7.4 mg/m3
      for the high and low exposure groups, respectively. The resolution was slightly
      less than for the original classification based on observations (15.0 and 7.1
      mg/m3). Surprisingly, the self reported presence of any ventilation device
      resulted in more contrast in mean exposure concentration between the groups (17.4
      and 7.5 mg/m3, respectively). Hairdressers reported validly on salon
      characteristics such as the type of salon, the number of hairdressers that worked
      in the salon, and the presence of ventilation devices, but could not make a
      distinction between different kinds of ventilation devices. The numbers of
      customers and tasks performed were largely overreported, but most variables
      correlated significantly with the information registered during the measurements.
      CONCLUSION: The self reported presence of any ventilation device is most
      predictive for the level of exposure to ethanol in the hairdressing salon.
      Questionnaire data on work characteristics should be treated with caution.

PMID- 9536163
TI  - Female seafarers adopt the high risk lifestyle of male seafarers.
AB  - OBJECTIVE: To study the mortality of women in an occupation known to have a high
      mortality among men. METHODS: A total of 6788 female seafarers of all job
      categories who had been employed on Danish merchant ships, passenger ships, and
      privately owned ferries between 1986 and 1993, were followed up until the end of
      1993. RESULTS: Standardised mortality ratio (SMR) was 1.20 (95% confidence
      interval (95% CI) 0.89 to 1.58) for all causes of death and job categories
      together. For women in traditionally male jobs, SMR was 2.82 (1.41-5.05), whereas
      galley and catering staff had SMRs close to the general female population. The
      high mortality among women in traditional male jobs could be explained by a high
      risk of fatal accidents including occupational accidents. In the whole cohort,
      there were fewer deaths from natural causes than expected but an excess risk of
      death due to lung cancer, heart diseases, and non-natural deaths. CONCLUSION: The
      increased mortality could primarily be explained by an excess risk of fatal
      accidents and suicide. Especially, female seafarers entering traditional male
      jobs had a high risk of fatal accidents, not only at sea but also ashore. An
      excess risk of dying of lung cancer and heart diseases probably reflects a high
      tobacco consumption. Female seafarers are probably influenced by their occupation
      towards hazardous behaviour and a high risk lifestyle but people with a high risk
      lifestyle may also be attracted by or forced into high risk jobs such as
      traditional male jobs at sea.

PMID- 9536162
TI  - Breast cancer risk and lifetime occupational history: employment in professional
      and managerial occupations.
AB  - OBJECTIVE: In this case-control study, occupational histories were used to assess
      the relation between risk of breast cancer and employment in professional and
      managerial occupations while adjusting for reproductive and other risk factors.
      METHODS: Incident, primary, female cases of breast cancer diagnosed between 1986
      and 1991, and randomly selected controls were interviewed to obtain detailed
      medical, reproductive, and occupational histories. Mantel-Haenszel crude odds
      ratios (OR) and 95% confidence intervals (95% CIs) were used to estimate risk of
      breast cancer related to the job of longest duration. Unconditional logistic
      regression was used to estimate crude and adjusted ORs and 95% CIs associated
      with having ever been employed and duration of employment in a professional or
      managerial occupation. RESULTS: A non-significant threefold increase in risk was
      found among premenopausal women whose major job was in the occupational category
      of precision production, craft, and repair (95% CI 0.90 to 20.35). No increase in
      risk was found for premenopausal women whose major job was a managerial or
      professional occupation. However, an inverse relation between risk of
      premenopausal breast cancer and having ever held a professional or managerial job
      was observed (OR 0.53, 95% CI 0.34 to 0.82). This relation was strongest for
      women who worked one to 10 years (OR 0.47, 95% CI 0.29 to 0.77). Postmenopausal
      breast cancer was not related to professional and managerial employment.
      CONCLUSIONS: In this population, employment in professional and managerial
      occupations is not associated with postmenopausal risk of breast cancer, but
      seems to be related to a reduction in risk of premenopausal breast cancer.
      Methodological limitations of this study including response rates are discussed.

PMID- 9536164
TI  - Risks of silicosis in coalworkers exposed to unusual concentrations of respirable
      quartz.
AB  - OBJECTIVES: To describe the radiographic changes in coalworkers exposed to
      unusual concentrations of respirable quartz during the 1970s, and to relate these
      to exposure measurements. METHODS: Men who had worked at one Scottish colliery
      during the 1970s were invited to a health survey. Chest radiographs were taken
      from 547 subjects. Classifications of these films under the International Labour
      Organisation (ILO) 1980 scheme were related, by logistic regression, to existing
      data on individual men's exposures to respirable dust and quartz. RESULTS: Taking
      the median of the three readers' results on profusion of small opacities, 203 men
      (38%) showed progression of at least one profusion category on the 12 point
      scale, from the various 1970s surveys to the follow up in 1990-1. A total of 158
      men (29%) had a profusion of at least 1/0, and 47 (8.6%) of at least 2/1 at the
      follow up survey. Large opacities were recorded as present by at least two
      readers for 14 (2.6%) of the men. Profusion of small opacities was strongly
      related to exposures experienced in the 1970s, and more strongly for quartz than
      for the non-quartz fraction of the dust. Estimates of risk are presented over the
      range of quartz exposures experienced. CONCLUSIONS: The quartz exposures
      experienced by some men at this colliery have caused considerable progression of
      radiographic abnormalities since exposure ended. The data accumulated offer
      opportunities for further more detailed analyses to inform debate on occupational
      limits for quartz exposures, both in collieries and in other industries where
      there is exposure to quartz in mixed dust.

PMID- 9536165
TI  - Occupational exposure to solvents and hairy cell leukaemia.
AB  - OBJECTIVES: The role of occupational exposures in hairy cell leukaemia was
      investigated through a multicentre, hospital based, case-control study. This
      paper analyses the role of exposure to solvents other than benzene in hairy cell
      leukaemia. METHODS: The study included 226 male cases and 425 matched controls,
      exposure to solvents was evaluated by expert case by case review of the detailed
      data on occupational exposures generated by specific interviews. Also, exposure
      to solvents was evaluated with an independently constructed job exposure matrix
      (JEM). RESULTS: No association was found between hairy cell leukaemia and
      previous employment in a job exposed to solvents (odds ratio (OR) 0.9 95%
      confidence interval (95% CI) 0.6 to 1.3). ORs for the main occupational tasks
      exposed to solvents were around 1 and did not increase with the frequency or the
      duration of the tasks. No specific type of paint or glue was found to be
      significantly associated with hairy cell leukaemia. No association was found with
      exposure to solvents, taken as a whole, with either expert assessments or the
      JEM. No association was found with aromatic, chlorinated, or oxygenated subgroups
      of solvents. The ORs did not increase with the average intensity of exposure
      assessed by the experts, with the frequency of use, or with the duration of
      exposure. Finally, no association was found with non-occupational exposure to
      solvents. CONCLUSIONS: The study did not show any association between exposure to
      solvents and hairy cell leukaemia.

PMID- 9536166
TI  - Update of the morbidity experience of employees potentially exposed to
      chlorpyrifos.
AB  - OBJECTIVES: Chlorpyrifos, an organophosphate ingredient of several important
      insecticides, has been manufactured at The Dow Chemical Company for 25 years. A
      previous morbidity study among employees of The Dow Chemical Company found no
      increased prevalence of illness or symptoms among employees potentially exposed
      to chlorpyrifos from 1977 to 1985 compared with matched controls. The purpose of
      the current study was to update the original study to 1994, thereby increasing
      the statistical power. METHODS: In the present study, 496 potentially exposed
      subjects were identified and matched for age, race, sex, pay, and year of hire to
      911 control subjects. Morbidity data were abstracted from company medical
      records. RESULTS: The prevalence of peripheral neuropathy was not significantly
      increased among this group of employees potentially exposed to chlorpyrifos.
      Significantly increased prevalence odds ratios were identified for five
      diagnostic categories: diseases of the ear and mastoid process; acute respiratory
      infections; other diseases of the respiratory system; general symptoms, signs,
      and ill defined conditions; and symptoms, signs, and ill defined conditions
      involving the digestive system. There was a strong association of diagnosis with
      duration of observation period, indicating that the exposed workers were more
      likely than unexposed workers to have a diagnosis abstracted from the company
      medical records due to their longer mean period of follow up. Analyses by
      exposure classification and mean plasma cholinesterase activity did not show a
      dose response. CONCLUSIONS: These data do not support a cause and effect relation
      of the diagnoses mentioned and exposure to chlorpyrifos.

PMID- 9536167
TI  - Nurses, take control of your practice.

PMID- 9536168
TI  - Communication averts an overdose.

PMID- 9536169
TI  - An ounce of prevention.

PMID- 9536170
TI  - Respect and accountability.

PMID- 9536171
TI  - Using human insulin.

PMID- 9536172
TI  - Talking with patients and families about addiction.

PMID- 9536173
TI  - When to worry about adolescent angst. Helping parents to distinguish anxiety from
      something more serious.

PMID- 9536174
TI  - Older adults overlooked.

PMID- 9536175
TI  - Meeting the challenge of advance directives.

PMID- 9536176
TI  - A new look at urinary tract infection.

PMID- 9536177
TI  - When your patient doesn't want to leave.

PMID- 9536179
TI  - Clinical snapshop: septic shock.

PMID- 9536178
TI  - Professional practice: facts & impact.

PMID- 9536180
TI  - A visit from an angel.

PMID- 9536181
TI  - Emergency! Acetaminophen overdose.

PMID- 9536182
TI  - What to do when your patient uses illicit drugs.

PMID- 9536183
TI  - Welfare reform and health care.

PMID- 9536184
TI  - ANA spearheads latex allergy movement.

PMID- 9536185
TI  - Anger at God after a loved one dies.

PMID- 9536186
TI  - Exposure to bloodborne pathogens.

PMID- 9536187
TI  - Latex allergy: relevant to us all.

PMID- 9536188
TI  - Vulnerable populations: a continuing nursing focus.

PMID- 9536189
TI  - Depressive phenomena, physical symptom distress, and functional status among
      women with breast cancer.

PMID- 9536190
TI  - Conceptualizing vulnerable populations health-related research.
AB  - BACKGROUND: A conceptual model for vulnerable populations research relates
      resource availability and relative risk to health status. The model has a
      population-based focus that places responsibility for the collective health
      status of its citizens with the community. Vulnerable populations are social
      groups who experience limited resources and consequent high relative risk for
      morbidity and premature mortality. There is considerable research evidence to
      support the major relationships in the model. Conceptual links that need
      additional research are identified. CONCLUSIONS: The implications for research
      include a variety of methodological problems related to recruiting and retaining
      participants, instrumentation, and data collection. Research designs are needed
      that move beyond descriptive and epidemiological approaches to interventional and
      outcome studies. Ethical considerations take on special significance with
      vulnerable populations.

PMID- 9536191
TI  - The effect of a social support boosting intervention on stress, coping, and
      social support in caregivers of children with HIV/AIDS.
AB  - BACKGROUND: Caring for the human immunodeficiency virus (HIV)-infected child is
      challenging and affects the entire family system. Studies have shown that social
      support can mitigate caregiver stress and enhance coping; however, social support
      may not always result in a positive outcome for the recipient. OBJECTIVES: To
      measure caregiver stress, coping, and social support, and to test the effect of a
      social support boosting intervention on levels of stress, coping, and social
      support among caregivers of children with HIV/acquired immune deficiency syndrome
      (AIDS). METHODS: An experimental design was used with monthly social support
      boosting interventions implemented. The stratified randomized sample included 70
      primary caregivers of children with HIV/AIDS. The sample strata were seropositive
      caregivers (biological parents) and seronegative caregivers (foster parents and
      extended family members). Study measures included the Derogatis Stress Profile,
      Family Crisis Oriented Personal Evaluation Scale, and the Tilden Interpersonal
      Relationship Inventory. Data were analyzed using descriptive statistics and
      repeated measure MANOVA. RESULTS: Statistically significant differences between
      the experimental and control groups were found on changes in the dependent
      variables over time when caregiver strata were included as a factor in the
      analysis; no statistically significant results were found when caregiver strata
      were combined. Univariate Ftests indicated that the level of social support for
      caregivers who were seronegative in the experimental group was significantly
      different from seronegative caregivers in the control group and seropositive
      caregivers in both groups. No significant treatment group differences were found
      for seropositive caregivers. CONCLUSIONS: Seronegative caregivers derived
      substantial benefit from the social support boosting intervention. Seronegative
      caregivers who acquire a child with HIV/AIDS are confronted with a complex
      stressful situation; the critical need to enhance their social support is
      achievable through the intervention tested in this study.

PMID- 9536192
TI  - Mothers' potential for child abuse: the roles of childhood abuse and social
      resources.
AB  - BACKGROUND: The mechanism by which some victims of childhood abuse become abusive
      parents, whereas others do not, is not well understood. Previous empirical
      evidence indicates that social resources may modify the cycle of abuse or
      maladaptive parenting; however, the effects of different dimensions of social
      resources have not been compared. OBJECTIVES: To determine whether a measure of
      mothers' potential for physical child abuse was related to their retrospective
      reports of physical and sexual abuse before 18 years of age and to investigate
      the potential buffering effects of multiple dimensions of social resources on the
      relationship between childhood abuse and mothers' potential for physical child
      abuse. METHODS: The potential role of social resources as a moderator of the
      relationship between a history of childhood abuse and potential for physical
      child abuse was investigated in 206 low-income single mothers of young children.
      RESULTS: The levels of physical and sexual abuse in childhood were positively
      associated with the mothers' child abuse potential; sexual abuse displayed the
      strongest association. Compared with mothers who were not sexually abused in
      childhood, those reporting violent sexual abuse as children were almost six times
      more likely to have high potential for physically abusing their children. There
      was no evidence that any of the social resources modified the relationship of
      either type of childhood abuse with the mothers' potential for abuse. However,
      all four dimensions of social resources demonstrated significant main effects on
      child abuse potential. CONCLUSIONS: Low-income mothers face many stressors
      because of their lack of economic resources. This, coupled with a lack of social
      resources and a history of childhood abuse, makes low-income, single mothers
      particularly at risk for abusive parenting. The lives of these women and their
      children may be enhanced by assisting the women to improve their social resources
      which, ultimately, may reduce their potential for child abuse. Future research
      should focus on identifying factors that predict and/or modify the potential for
      abusive parenting as well as actual abuse.

PMID- 9536193
TI  - Self-schemas and possible selves as predictors and outcomes of risky behaviors in
      adolescents.
AB  - BACKGROUND: Although there is extensive evidence that the self-concept changes in
      many important ways during the adolescent years and that these changes influence
      behavioral choices, the majority of studies completed to date have been based on
      a static model in which the self-concept is viewed solely as an antecedent of the
      risky behaviors. OBJECTIVES: To investigate the pattern of relationships between
      three components of the self-concept--the popular, the conventional, and the
      deviant selves--and risky behaviors in a sample of middle adolescents during
      their transition from junior high to high school. METHODS: A sample of 160
      adolescents completed questionnaires measuring the content of their self-schemas
      and possible selves and involvement in four risky behaviors (tobacco and alcohol
      use, sexual intercourse, poor school performance) during the winter of eighth and
      ninth grades. RESULTS: Popular self-schema score in the eighth grade positively
      predicted ninth grade risky behaviors. Risky behavior involvement in the eighth
      grade predicted ninth-grade deviant self-schema and possible self-scores.
      CONCLUSIONS: These findings suggest that the self-concept may not only play a
      role in the early stages of engagement in the risky behaviors but may also be one
      means through which the behaviors become structuralized into potentially enduring
      aspects of the self.

PMID- 9536194
TI  - The experience of being a grandmother who is the primary caregiver for her HIV
      positive grandchild.
AB  - BACKGROUND: The number of grandparents assuming care for their grandchildren is
      increasing, and this affects grandparents both positively and negatively. The
      current study builds on an earlier study of the effects of social support,
      stress, and level of illness on caregiving of children with acquired immune
      deficiency syndrome (AIDS) that identified both positive and negative effects of
      caregiving. OBJECTIVES: To identify the lived experience of African American and
      Latino grandmothers as the primary caregivers for their grandchildren who are
      human immunodeficiency virus (HIV)-infected or have AIDS and to identify the
      similarities and differences between the two groups. METHODS: Using Van Manen's
      method for hermeneutical phenomenological research, the lived experiences of 10
      African American and Latino grandmothers who were the primary caregivers for
      their HIV-positive grandchildren were investigated. Additionally, the
      similarities and differences between the two groups were studied. RESULTS: Four
      themes identified were (a) upholding the primacy of the family, (b) living in the
      child-centered present, (c) being strong as mature women, and (d) living within a
      constricting environment. Twelve subthemes expanded and clarified the meaning of
      these themes. CONCLUSIONS: Although there were differences related to family
      structure and cultural backgrounds, the grandmothers were more alike than
      different.

PMID- 9536195
TI  - Maternal employment and parent-child relationships in single-parent families of
      low-birth-weight preschoolers.
AB  - BACKGROUND: The influence of premature birth of an infant in female-headed,
      single-parent families together or in conjunction with family environment
      factors, such as employment of the mother, on the mother-premature child
      relationship has not been considered in past studies. OBJECTIVES: To explore
      differences in parent-child and family relationships for employed and nonemployed
      single mothers of low-birth-weight (LBW) and full-term preschool children and to
      describe the relationships of the mother's employment status, employment history,
      and employment attitude-behavior consistency to parent-child and family
      relationships. METHODS: Single mothers with LBW (n = 60) and full-term (n = 61)
      preschool children provided data on their employment situation, the Parenting
      Stress Index, the Feetham Family Functioning Survey, and the Home Observation for
      Measurement of the Environment. RESULTS: Employed mothers had more positive
      perceptions and provided more enriching home environments for their children.
      Greater attitude-behavior consistency was associated with more positive
      perceptions of the parental role. CONCLUSION: Thus, in single-parent families,
      employment and consistency are positive influences on the mother-child
      relationship.

PMID- 9536197
TI  - HIV/AIDS, micro-ethics and macro-ethics.

PMID- 9536196
TI  - Commitment and communication: keys to minimizing attrition in multisite
      longitudinal organizational studies.

PMID- 9536198
TI  - Social care of children born to HIV-infected mothers in Europe. European
      Collaborative Study.
AB  - Children of HIV-infected women are likely to be profoundly affected by their
      mothers' infection, regardless of their own infection status and their number
      will increase with the spread of infection among women in Europe. This article
      describes the family circumstances and social care of 1,123 children born to HIV
      infected women enrolled in the European Collaborative Study and followed
      prospectively from birth. Most mothers were white, married or cohabiting,
      asymptomatic and had a history of drug use, with 45% currently using injecting
      drugs at the time of enrollment. Seventy percent of children were cared for by
      their mothers and/or fathers consistently in their first four years of life, but
      by age eight an estimated 60% will have lived away from their parents (i.e. with
      foster or adoptive parents, other relatives or in an institution). Whether or not
      a child was infected did not influence the likelihood of living in alternative
      care. Maternal injecting drug use, single parenthood and health status were the
      major reasons necessitating alternative care. The type of alternative care varied
      according to maternal characteristics, child's age and geographic location. The
      mothers of 98 children had died and average age at maternal death was four years.

PMID- 9536199
TI  - Secondary prevention for youths living with HIV.
AB  - As the number of youths infected with HIV rises, secondary prevention programmes
      are needed to help youths living with HIV meet three goals: (1) increase self
      care behaviours, medical adherence and health-related interactions; (2) reduce
      transmission acts; and (3) enhance their quality of life. This article describes
      an intervention programme for youths living with HIV, delivered over 30 sessions,
      in three modules. Based on modifications of the social action model, perceptions,
      attitudes and skills to enhance affective awareness and positive behavioural
      routines are identified as prerequisites for meeting each of the targeted
      outcomes. In each module, youths engage in small-group activities over 8-12
      sessions with other infected peers to modify their behavioural patterns. Module 1
      focuses on choosing one's social identity with respect to a seropositive status,
      implementing new daily routines to stay healthy, coping with receiving high
      quality medical care and keeping safe from reinfection. Module 2 aims to reduce
      substance use and unprotected sexual acts. Module 3 focuses on using sensory
      awareness as a strategy for enhancing the quality of life. A variety of delivery
      strategies are discussed for secondary interventions.

PMID- 9536200
TI  - Safe sex or safe love: competing discourses?
AB  - The way in which sex may be constructed as safe through its relationship with
      'love' is the concern of this study. Interviews with 112 heterosexual women and
      men from discos and bars in Melbourne, Australia, catering to single adults
      revealed the pervasive construction of sex within the discourses of 'love' and
      'romance'. The relationship of these discourses to unsafe practices is discussed
      and the article presents an analysis of the normative function of the sex-as
      love/sex-as-desire opposition in terms of safe sex and HIV/AIDS prevention. We
      conclude that health messages which emphasize that 'sex is unsafe' may be
      counterproductive. We illustrate how women and some men construct casual sex as a
      strategy for obtaining the possibility of 'love'. For these women and men, 'safe
      sex' as 'unprotected sex' is viewed as a strategy for maximizing the possibility
      that the casual encounter will result in a longer term relationship. On the other
      hand, 'unsafe sex' as 'unprotected sex' is viewed as a strategy that is more
      likely to interrupt the construction of romance in the causal encounter thus
      risking the possibility of love as the desired outcome.

PMID- 9536201
TI  - The role of disclosure in coping with HIV infection.
AB  - A qualitative investigation was conducted to explore the role of disclosure in
      HIV infection. Forty homosexual and bisexual men completed a short demographic
      questionnaire and participated in a one-to-one, semi-structured interview. The
      interview was designed to address a variety of personal, interpersonal and
      organizational issues related to their HIV status and participants were invited
      to talk about their personal experiences from immediately prior to their
      diagnosis to the time of the interview. The results from the interviews are
      presented in three sections: immediately post-diagnosis, asymptomatic phase and
      symptomatic/AIDS phases. The data revealed that disclosing one's HIV status was
      an acute and recurrent stressor. Immediately post-diagnosis, individuals were
      more likely to adopt a policy of non-disclosure and this provided them with an
      opportunity to come to terms with their diagnosis before having to contend with
      the reactions of others. After this phase, there was evidence that individuals
      increasingly used disclosure as a mechanism for coping with the disease.
      Disclosure of one's status was used to increase both practical and emotional
      support, share responsibility for sex and to facilitate self-acceptance of one's
      condition. The results from this investigation revealed that disclosure has a
      dual role in HIV infection acting as both a stressor and a mechanism by which
      individuals contend with their infection.

PMID- 9536202
TI  - A multicentre study on the causes of death among Italian injecting drug users.
      AIDS has overtaken overdose as the principal cause of death.
AB  - The causes of death among injecting drug users. (IDUs) are still being discussed
      worldwide. We analysed the causes of death among IDUs attending 26 centres for
      drug users in North-Eastern Italy from 1985 to 1994. The study of a total number
      of 1,022 deaths reveals the following: (1) AIDS has become the primary cause of
      death among IDUs since 1991 and is rising even in an area with a moderate HIV
      seroprevalence; (2) the mean age of death in AIDS patients proved higher than
      among patients who died of other causes (which may be due to the long incubation
      period of AIDS); (3) our data do not reveal higher HIV seroprevalence among IDUs
      who died of overdose and suicide as opposed to IDUs who died of other causes; (4)
      the mortality rate in IDUs is significantly higher when compared to that of the
      general population in the same age group.

PMID- 9536203
TI  - Changes in prostitution and the AIDS epidemic in Thailand.
AB  - The HIV/AIDS epidemic which broke out in Thailand 1988 was mainly caused by the
      widespread patronage of prostitutes. The Thai authorities responded with
      programmes which encouraged the use of condoms in commercial sex. These
      programmes were highly successful. However, prostitution has changed since the
      beginning of the epidemic, partly for economic and demographic reasons, but
      mainly because of the fear of AIDS. Fewer women practise prostitution, men
      patronize it less, and the price of commercial sex has risen. Prostitution is
      less likely to be practised in brothels and more likely to be practised in
      establishments like restaurants and bars. Moreover, as fewer native Thai women
      are willing to practise prostitution, foreign women are taking their place. In
      order to continue to control the epidemic, the authorities will have to adapt
      their programmes to the changing structure of commercial sex.

PMID- 9536204
TI  - Safer sex and social class: findings from a study of men using the 'gay scene' in
      the West Midlands region of the United Kingdom.
AB  - This article reports on associations between socio-demographic factors and safer
      sexual behaviour among gay and bisexual men in an English region. A cross
      sectional survey using an anonymous self-complete questionnaire collected
      information on sexual behaviour and socio-demographic characteristics. All men
      using specified 'gay' venues and groups during the data collection period, were
      offered inclusion. Of the 858 men returning completed questionnaires, a greater
      proportion (30.3%) were from manual occupations when compared to previous United
      Kingdom studies. Of the whole sample, 64.6% reported either consistent condom use
      (safer sexual behaviour) or no anal sex during the last 12 months. No
      associations were found between age or ethnicity and consistency of condom use.
      Social class and employment status, however, were associated: those in manual
      occupations and those not working were more likely to be inconsistent in their
      condom use and students were more likely to be consistent. Inconsistent condom
      use was more likely to occur when having anal sex with 'boyfriends', and data on
      relationship length suggest that this may be occurring inappropriately in
      relation to risk of HIV infection. These findings suggest that social class and
      employment status may be related to safer sex practice.

PMID- 9536205
TI  - Comparison of the clientele of an anonymous HIV test centre and persons tested in
      the general population.
AB  - This study compares the clientele of a Swiss anonymous test centre with the
      general population tested. Information was obtained through similar
      questionnaires submitted to two samples of HIV-tested people aged from 17 to 45
      years: the first administered in the context of a general population telephone
      survey (n = 245) and the second completed during face-to-face interviews of the
      clientele of an anonymous test centre (n = 250). The test centre sample has
      higher proportions of younger and single people. Attenders for anonymous testing
      were more likely to have acquired a new regular partner during the year preceding
      the interview (48.0% versus 14.4%). These differences remain when controlling for
      age and gender. Decision to test comes mostly from the respondent's own
      initiative, but suggestion from a doctor is more frequent in the general
      population (23.8% versus 0.8%), whereas suggestion from partner or friends is
      more frequent in the anonymous centre (44.4% versus 3.0%). The anonymous test
      centre clientele is not different from the general population tested except for
      the relational situation and origin of decision for testing. The test centre has
      become a place where the general population finds a response to a situation
      specific need for HIV testing.

PMID- 9536206
TI  - 'Unsafe protected sex': qualitative insights on measures of sexual risk.
AB  - To describe forms of unsafe protected sex (vaginal or anal intercourse where
      condoms are used unsafely) among a sample of drug users in London, data are drawn
      from a qualitative study of the sexual and drug taking lifestyles of opioid and
      stimulant users. Depth one-to-one interviews (n = 96) elicited detailed
      descriptions from interviewees of their sexual behaviour, including the last
      occasions they had protected and unprotected sex. Analysis of these accounts
      identified the phenomenon of 'unsafe protected sex' (UPS). Three forms of UPS
      were identified: (1) Condoms for ejaculation only. This is where a condom was
      used for penetrative sex, but only when ejaculation was imminent. In these
      situations, the perceived function of the condom related more to the prevention
      of unwanted pregnancy than the prevention of HIV/STDs. (2) Condoms after limited
      unprotected penetration. This is where sexual partners commenced unprotected
      penetration but used a condom soon after. Participants tended to see such
      unprotected penetration as a coerced or collaborative transgression from their
      usual safer sexual practices. (3) Condom failure. This is where condoms split or
      came off during penetration. This was sometimes only discovered after ejaculation
      and withdrawal, and was invariably perceived by participants to have been unsafe.
      The likelihood of condom failure may be increased in penetrative sex prolonged
      through the use of drugs. Findings point to the possibility that surveys of
      sexual risk behaviour underestimate levels of unprotected and unsafe sex. A
      broader and more sophisticated definition of 'sexual risk behaviour' is required
      with regard to condom use, one which incorporates UPS. If some forms of UPS are
      perceived to be 'safer sex', future interventions need to highlight the STD
      transmission risks associated with this activity. Also, some people may view UPS
      as a transgression towards unsafe behaviour, and this may be proffered as a
      rationalization for not using condoms at all.

PMID- 9536207
TI  - Psychological and socio-medical aspects of HIV/AIDS: a reflection on publications
      in AIDS care (1989-1995).
AB  - It is necessary to consider the content and methods of AIDS social research
      publications for these represent research advances as well as current issues of
      concern for practitioners, communities and researchers alike. This article
      critically examines some of the research that has been conducted to date into
      social aspects of HIV and AIDS. It quantifies the content and major
      methodological style of publications in the journal AIDS Care from 1989 to 1995.
      The most commonly published topic area in AIDS Care, during this period was
      cultural and demographic issues (15.9%), followed by issues pertinent to the
      psychological impact of HIV (13.6%), sexual behaviour and condom use (11.3%) and
      policy and services (9.5%). Research and measurement issues were the least
      examined content area in AIDS Care 1989-1995 (2.6%). This article discusses
      possible variables that influence the style and topics that are published in AIDS
      Care and makes suggestions for authors to consider before embarking on future
      research projects or publications.

PMID- 9536208
TI  - The regulatory biology of the human pilosebaceous unit.
AB  - The last few years have witnessed an acceleration in our understanding of the
      regulation of the human pilosebaceous unit. Recombination and histochemical
      experiments are beginning to elucidate the role of homeotic genes, transcription
      factors, growth factors and adhesion molecules in pilosebaceous embryology.
      Histochemical studies, experiments in gene-modified animals, and in vitro studies
      on growing human hairs, have identified a number of growth factors that are
      central to normal hair growth. Thus epidermal growth factor and transforming
      growth factor-alpha appear to be involved in the triggering of both anagen and
      catagen. Insulin-like growth factor-I appears to sustain normal anagen growth,
      transforming growth factor-beta will inhibit anagen growth, while interleukin-1
      alpha and tumour necrosis factor-alpha will induce matrix cell death. These
      complex growth factor effects are beginning to be moulded into an integrated
      model of pilosebaceous regulation. The role of steroid hormones in modulating
      these growth factor effects is also beginning to be understood.

PMID- 9536209
TI  - A critical review of the origin and control of adrenal androgens.
AB  - The reticularis and fasciculata zones of the adrenal cortex are the predominant
      sources of dehydroepiandrosterone (DHEA) and DHEA-sulphate and contribute
      directly or indirectly 60-75% of androstenedione and testosterone in women. The
      specific control of adrenal androgens remains unclear. While ACTH stimulates
      adrenal androgen secretion, the dissociation of cortisol and androgens occurring
      during adrenarche and under pathological conditions suggests other factors are
      involved. Recent studies using human adrenal cells in vitro have demonstrated
      that the ratio of androgen to cortisol produced is substantially independent of
      the age and gender of the adrenal, indicating that extra-adrenal factors are of
      greater importance. beta-Endorphin and joining peptide have been shown to
      stimulate androgen production in human adrenal cells and to influence ACTH
      stimulated steroidogenesis in a manner that promotes adrenal androgen production.
      The activity of these pro-opiomelanocortin-derived peptides may explain the
      physiological and pathological dissociations of androgens and cortisol.

PMID- 9536210
TI  - Role of androgens in follicle maturation and atresia.
AB  - Androgens are products of progestogen metabolism, intermediates in oestrogen
      biosynthesis and local regulators of ovarian function. Current understanding of
      intraovarian androgen formation, metabolism and action is reviewed, highlighting
      the contribution of androgens to the paracrine regulation of follicular
      maturation and atresia. Any factor that alters intracellular cAMP levels is a
      potential modulator of granulosa cell differentiation, and hence follicular
      development. Androgen appears to modulate gonadotrophin action on granulosa cells
      through amplification of cAMP-mediated post-receptor signalling. Here it is
      argued that during intermediate stages of follicular development, locally
      produced androgen acts via granulosa cell androgen receptors (AR) to promote
      follicle-stimulating hormone (FSH)-induced granulosa cell differentiation through
      amplifying cAMP-mediated post-receptor signalling. During late pre-ovulatory
      follicular development, higher concentrations of cAMP caused by stimulation with
      luteinizing hormone (LH) suppress granulosa cell proliferation and down-regulate
      some of the genes induced by FSH at earlier stages of pre-ovulatory development,
      including aromatase activity. Other granulosa cell functions, including
      progesterone synthesis, are enhanced by the high concentrations of cAMP induced
      by LH. There is experimental evidence from studies of rat and non-human primate
      (common marmoset) ovaries that AR levels in granulosa cells decline during pre
      ovulatory follicular maturation. Since androgens augment FSH-induced cAMP
      formation and action, loss of AR could be a means of avoiding inappropriately
      high cAMP levels and hence avoiding premature activation of 'high-tone' cAMP
      response genes that lead to atresia. Negative regulation of the granulosa cell AR
      could be part of the intra-ovarian mechanism that determines which follicle(s)
      becomes dominant and secretes oestrogen in the normal menstrual cycle.

PMID- 9536211
TI  - Local control of ovarian steroidogenesis.
AB  - A number of putative paracrine factors are now thought to interact with FSH in
      the control of ovarian steroidogenesis. The relative importance of these factors
      remains to be determined, but the presence of the insulin-like growth factors and
      their binding proteins and the mechanism of control of the latter through the
      local production of proteases suggests a role for this system in
      folliculogenesis. We have demonstrated over-production of steroid hormones in
      tissue from women with polycystic ovaries. Theca cells in monolayer culture
      produced excessive amounts of progesterone and androstenedione and granulosa cell
      oestradiol production was considerably enhanced in response to FSH. Recent
      evidence points to a genetic defect in the expression or translation of
      steroidogenic hormones as a cause of excess androgen production, but the gene or
      genes involved has not been established. Data from our group suggest that
      granulosa cells from anovulatory polycystic ovaries are prematurely matured and
      we hypothesize that this is due to the interaction of the raised circulating
      insulin levels with LH in these follicles, an interaction that results in
      arrested follicular growth.

PMID- 9536212
TI  - Congenital adrenal hyperplasia.
AB  - A clinical spectrum, varying from prenatal onset to postnatal onset of symptoms,
      exists in all hyperandrogenic forms of congenital adrenal hyperplasia (CAH).
      Postnatal onset hyperandrogenic symptoms such as premature pubarche,
      clitoromegaly, hirsutism, menstrual disorders and infertility are well known
      manifestations of CAH due to 21-hydroxylase deficiency, 3 beta-hydroxysteroid
      dehydrogenase deficiency or 11 beta-hydroxylase deficiency. These hyperandrogenic
      symptoms of CAH are clinically indistinguishable from other causes of
      hyperandrogenism. The molecular data has proven the genetic basis for the
      phenotypic variability of CAH disorders. Specific hormonal criterion(a) defined
      by the molecular proof of the disorder should aid in discriminating between
      symptomatic patients due to CAH and other causes, and between those with mild and
      severe CAH disorders. Prevalence of the hyperandrogenic forms of CAH, as well as
      pubertal maturation and reproductive function in women with hyperandrogenic forms
      of CAH, are discussed.

PMID- 9536213
TI  - Current concepts of polycystic ovary syndrome.
AB  - Polycystic ovary syndrome (PCOS) may be loosely defined as unexplained
      hyperandrogenism, with variable degrees of cutaneous symptoms, anovulatory
      symptoms, and obesity. The vast majority of patients with the full-blown Stein
      Leventhal syndrome have functional ovarian hyperandrogenism (FOH). However, FOH
      often occurs without the LH excess or polycystic ovaries of classic PCOS.
      Functional adrenal hyperandrogenism (FAH) is often found in the syndrome, but it
      is less closely associated with anovulatory symptoms than is FOH. The vast
      majority of FOH seems to arise from abnormal regulation (dysregulation) of
      ovarian androgen secretion. This typically is due to escape from desensitization
      to luteinizing hormone (LH); this appears to occur because of a breakdown in the
      processes that normally coordinate ovarian androgen and oestrogen secretion so as
      to prevent hyperoestrogenism. Similar dysregulation of adrenal androgen secretion
      in response to ACTH seems to account for most FAH. Dysregulation of androgen
      secretion may affect the ovary alone (isolated FOH), the adrenal alone (isolated
      FAH), or both together. Modest insulin resistance is common in PCOS/FOH, and the
      resultant hyperinsulinaemia is a major candidate as the cause of the
      dysregulation. The hyperinsulinaemia may arise from either 'nature' (genetic
      defects) or 'nurture' (exogenous obesity). Although hyperinsulinaemia alone does
      not have an obvious effect on steroidogenesis, it may act in genetically
      predisposed women as a 'second hit' to unmask latent abnormalities in
      steroidogenesis. The ovary, the adrenal cortex, and several other organs
      paradoxically function as if responding to the hyperinsulinaemic state in spite
      of resistance to the effects of insulin on glucose metabolism. PCOS should be
      viewed as an early manifestation of a hyperinsulinaemic condition that will
      predispose to cardiovascular and metabolic complications later in life. A subset
      of PCOS patients appear to have not only insulin resistance but also beta-cell
      secretory dysfunction, which may indicate a relationship of the disorder to
      NIDDM. The fundamental genetic defects remain to be elucidated.

PMID- 9536214
TI  - Relation of functional ovarian hyperandrogenism to non-insulin dependent diabetes
      mellitus.
AB  - Up to 40% of women with polycystic ovary syndrome (PCOS) demonstrate some degree
      of glucose intolerance, either impaired glucose tolerance (IGT) or non-insulin
      dependent diabetes mellitus (NIDDM). Defects in insulin action have long-been
      recognized as characteristic in these women. Recently, evidence has been obtained
      which documents that insulin secretory dysfunction also contributes significantly
      to the observed glucose intolerance. This chapter will focus on the recent
      evidence supporting the specific roles of disordered insulin secretion and
      action, in the development of glucose intolerance in PCOS. In addition, the use
      of pharmacological agents that modify insulin action as therapeutic options for
      women with PCOS, will be discussed.

PMID- 9536215
TI  - Definition and significance of polycystic ovaries.
AB  - Defining the polycystic ovarian syndrome (PCOS) has challenged clinicians for
      many years. The clinical, hormonal and morphological definitions of PCOS have
      their own limitations and do not correspond exactly. Clinically, PCOS can be
      schematically divided into three components, i.e. hyperandrogenic, anovulatory
      and dysmetabolic. No one is specific for the syndrome. Hormonally, PCOS has
      recently been defined by the GnRH agonist test as a functional abnormality in
      ovarian androgen synthesis. This functional ovarian hyperandrogenism seems
      closely linked to hyperinsulinism secondary to an insulin resistance.
      Morphologically, ovarian ultrasonography has emerged in the last decade or so as
      a new diagnostic tool. However, the sonographic definition of the polycystic
      ovary (PCO) is controversial, mainly because of a lack of consensus about
      normative data. The aim of this review is to present the diagnostic dilemma in
      the diagnosis of PCOS and to discuss the prognostic significance of the PCO.

PMID- 9536216
TI  - Diagnosis and therapy of hyperandrogenism.
AB  - Diagnostic categories in hyperandrogenism include polycystic ovary syndrome
      (PCOS) and its variants, adrenal and ovarian steroidogenic enzyme deficiencies,
      adrenal and ovarian androgen secreting tumours and other endocrine disorders such
      as hyperprolactinaemia, Cushing syndrome and acromegaly. About 95% of
      hyperandrogenic women will have PCOS. Endometrial hyperplasia can be prevented in
      hyperandrogenic, anovulatory women by the oral contraceptive pill or progestins.
      Hirsutism is best treated by a combination of the oral contraceptive pill and an
      anti-androgen. The first line of therapy for ovulation induction is clomiphene
      citrate, with human menopausal gonadotrophins (hMG) or laparoscopic ovulation
      induction reserved for clomiphene failures. hMG together with gonadotrophin
      releasing hormone agonist may decrease the risk of spontaneous abortion following
      ovulation induction in PCOS. Weight loss should be vigorously encouraged to
      ameliorate the metabolic consequences of PCOS.

PMID- 9536217
TI  - T-cell receptor variable region genes in cutaneous T-cell lymphomas.
AB  - The genes encoding the T-cell receptor (TCR) variable beta (TCRBV) regions were
      studied in skin biopsy samples from 24 patients with cutaneous T-cell lymphomas
      (CTCL), i.e. mycosis fungoides (n = 7), Sezary syndrome (n = 4), lymphomatoid
      papulosis (n = 3) and large cell CTCL with (n = 3) or without (n = 7) CD30
      expression. A panel of 24 primers specific for TCRBV families 1-24 was designed
      and applied to cDNA using a semiquantitative reverse transcriptase coupled
      polymerase chain reaction (PCR) method. Three patients showed restricted
      expression of a limited number (1-3) of TCRBV families. In the remaining
      patients, an average of 17 (range: 13-22) different families was expressed. All
      patients showed elevated (> 10%) expression of individual families significantly
      higher than that seen in normal blood lymphocytes, but no preferential usage of
      particular gene families was observed. Direct sequence analysis of more than 60
      PCR products revealed clonal TCR transcripts in 18 patients. A single T-cell
      clone, constituting 9-100% (mean: 26%) of the TCRBV mRNA, was present in 12
      patients; two T-cell clones, constituting 13-72% (mean: 21.5%) of the TCRBV mRNA,
      were present in five patients; and three T-cell clones, accounting for < 0.5-13%
      of the TCRBV mRNA, were present in one patient. In the remaining six patients,
      clonal TCR transcripts could not be identified. It is concluded that most CTCL
      contain both clonal and non-clonal (reactive) T cells, and that the latter cells
      are more numerous than anticipated. These cells may be engaged in tumour immune
      reactions, although prospective studies and/or serial investigations are needed
      to elucidate this issue fully.

PMID- 9536218
TI  - Homozygous deletion of the p16INK4a and the p15INK4b tumour suppressor genes in a
      subset of human sporadic cutaneous malignant melanoma.
AB  - Chromosome 9p21 is frequently deleted in malignant melanoma, and one familial
      malignant melanoma gene has been linked to 9p21-22. Recently, the cyclin D
      dependent kinase inhibitors (CDKIs) p16INK4a and p15INK4b have been localized
      within chromosome 9p21, and the presence of p16INK4a point mutations has been
      demonstrated in familial melanoma and melanoma cell lines in vitro. To analyse
      the role of these CDKIs in sporadic human cutaneous non-metastatic malignant
      melanoma, we examined 36 primary tumour specimens representing different stages
      of melanoma progression and their corresponding normal skin samples for the three
      mechanisms of CDKI inactivation described so far. Homozygous codeletion of the
      p16INK4a and the p15INK4b gene was detected by Southern blot analysis in two
      tumour samples. By direct sequencing of polymerase chain reaction (PCR)-amplified
      microdissected genomic DNA; no somatic or germline p16INK4a point mutations or
      small deletions were detected in the remaining 34 tumour samples; one individual
      exhibited the previously described germline codon 148 (Ala-->Thr) polymorphism.
      In these tumour specimens, comparative semiquantitative reverse PCR analysis of
      p16INK4a transcript levels revealed no evidence for repression of p16INK4a gene
      transcription and thus for p16INK4a promoter inactivation by DNA methylation.
      These results indicate homozygous p16INK4a and p15INK4b loss to occur in a subset
      of cutaneous melanomas and suggest, in view of the frequent loss of
      heterozygosity on chromosome 9p21, the presence of another tumour suppressor gene
      within this chromosomal region.

PMID- 9536219
TI  - Plasminogen activator inhibitor type 2 is expressed in keratinocytes during re
      epithelialization of epidermal defects.
AB  - Plasminogen activation is observed in the human epidermis during re
      epithelialization of epidermal defects. The activation reaction depends on
      plasminogen activators (PAs) associated with re-epithelializing keratinocytes. PA
      inhibitor type 2 (PAI-2) is thought to be a major epidermal PA inhibitor in
      keratinocytes. However, no data are available on the expression of PAI-2 in
      keratinocytes during epidermal regeneration. We have therefore analysed PAI-2 at
      the mRNA and protein level in keratinocyte cultures as well as in epidermal
      lesions in which re-epithelializing keratinocytes were apparent. We found that
      PAI-2 expression at the mRNA and protein level was negatively correlated with the
      cell density in regular keratinocyte cultures. In organotypic cocultures, in
      which the transition from a re-epithelializing to a sedentary phenotype can be
      studied, PAI-2 was most strongly expressed in early cultures prior to formation
      of a differentiated epidermis-like structure. We found a strong expression of PAI
      2 in keratinocytes that re-epithelialized dermal burn wounds or lesions caused by
      the autoimmune blistering disease pemphigus vulgaris. Our results suggest that
      not only PAs, but also a major PA inhibitor, PAI-2, are expressed in
      keratinocytes that are actively involved in re-epithelialization.

PMID- 9536220
TI  - Suprabasal expression of epidermal alpha 2 beta 1 and alpha 3 beta 1 integrins in
      skin treated with topical retinoic acid.
AB  - In normal adult human skin, expression of epidermal integrins is confined to
      keratinocytes in the basal layer. However, suprabasal expression of alpha 2,
      alpha 3 and beta 1 integrin subunits is noted in hyperproliferative epidermis in
      wound repair and psoriasis. In this study, we examined the effect of topical all
      trans-retinoic acid (RA), known to induce epidermal hyperplasia, on expression of
      integrins in human epidermis. Immunostaining of vehicle-treated skin revealed
      expression of alpha 2, alpha 3 and beta 1, as well as alpha 6 and beta 4 integrin
      subunits entirely on basal keratinocytes. Topical application of RA (0.1%) for 2
      weeks resulted in marked suprabasal expression of alpha 2, alpha 3 and beta 1
      integrin subunits, whereas alpha 6 and beta 4 staining remained on basal
      keratinocytes. Staining for putative ligands of alpha 2 beta 1 and alpha 3 beta 1
      integrins, i.e. type IV collagen, laminin-5 and fibronectin, was not detected in
      the epidermal layer in RA- or vehicle-treated skin. Treatment of HaCaT
      keratinocytes in culture with RA (1 mumol/L) enhanced alpha 2 and beta 1 mRNA
      abundance. Furthermore, RA slightly up-regulated the expression of alpha 2, alpha
      3 and beta 1 integrin subunits on primary epidermal keratinocytes and HaCaT cells
      in culture with no effect on cell proliferation. These results provide evidence
      that RA-elicited epidermal hyperplasia is associated with aberrant suprabasal
      expression of alpha 2 beta 1 and alpha 3 beta 1 integrins, and that this also
      involves direct stimulation of keratinocyte integrin expression by RA.

PMID- 9536221
TI  - Expression of transglutaminase 1 in human hair follicles, sebaceous glands and
      sweat glands.
AB  - To explore the function of the enzyme transglutaminase 1 (TGase 1), its
      distribution was analysed by immunofluorescence microscopy, postembedding
      immunoelectron microscopy and in situ hybridization. TGase 1 was expressed in the
      outer root sheath (ORS) cells in the distal portion of the isthmus and
      infundibulum of human hair follicles. In the level of the proximal and middle
      portion of the isthmus, TGase 1 was observed in the keratinized area of the inner
      root sheath (IRS) and ORS cells. In the bulbar and suprabulbar portions, TGase 1
      was present in the ORS and IRS cells. The cortex and medulla cells in these
      regions also contained TGase 1. A high level of fluorescence was observed at the
      cuticle of the cortex. Sebaceous and sweat gland cells contained abundant TGase
      1. Possible functions of TGase 1 in these epidermal appendages are discussed.

PMID- 9536222
TI  - The participation of proliferative keratinocytes in the preimmune response to
      sensitizing agents.
AB  - The aims of this study were to investigate whether keratinocytes are capable of
      playing a direct preimmune role in the pathophysiology of allergic contact
      dermatitis (ACD) and to examine to what extent the degree of differentiation
      might influence this. We measured the ability of sensitizing agents to up
      regulate intercellular adhesion molecule 1 (ICAM-1) expression in cultured normal
      human keratinocytes (NHK) and in the transformed human keratinocyte HaCaT cell
      line. In proliferative HaCaT cells, following a 24 h exposure, nickel compounds,
      para-phenylenediamine (pPD) and 1-chloro-2,4-dinitrobenzene produced a
      concentration-dependent up-regulation of ICAM-1 expression without reducing cell
      viability, while K2Cr2O7 led to ICAM-1 up-regulation at cytotoxic concentrations,
      and CrCl3 was without effect. In NHK, NiSO4 and pPD induced ICAM-1 expression to
      a significantly greater extent in proliferative cells than in differentiated
      cells, where involucrin expression was measured to assess the differentiation
      state. NiSO4- or pPD-pretreatment of proliferative HaCaT cells enhanced T-cell
      binding, which was abolished by neutralizing antibodies to ICAM-1 or CD18. Our
      investigations concerning the involvement of oxidative stress in the induction of
      ICAM-1 expression in response to sensitizing agents were inconclusive. The
      oxidizing agents FeCl3 and H2O2 up-regulated ICAM-1 expression in HaCaT cells but
      there was no clear relationship between the ability of agents to induce ICAM-1
      expression and their ability to alter the levels of reduced glutathione. Although
      pPD increased interleukin-1 alpha release from NHK, this cytokine was not capable
      of inducing ICAM-1 expression in NHK. Tumour necrosis factor-alpha, which does
      induce ICAM-1 expression in NHK, was not detected in response to pPD, arguing
      against an autocrine pathway of ICAM-1 induction in response to pPD. In summary,
      we report the direct interaction of sensitizing agents with keratinocytes leading
      to the generation of immune signals, particularly by proliferative keratinocytes,
      suggesting an active role for the proliferative keratinocyte in the
      pathophysiology of ACD.

PMID- 9536223
TI  - Down-regulation of transforming growth factor-beta receptors I and II is seen in
      lesional but not non-lesional psoriatic epidermis.
AB  - Transforming growth factor-beta s (TGF-beta s) are a family of growth factors
      with inhibitory effects on epithelial cell proliferation. Their effects are
      mediated by two interacting receptors, of which type I (T beta R-I) mediates
      signal transduction after interaction with type II (T beta R-II) carrying the TGF
      beta ligand. We have studied the expression of T beta R-I and T beta R-II in
      psoriatic and normal human skin by using polyclonal rabbit antisera and
      immunohistochemistry. Immunohistochemical analysis revealed an intense
      immunoreactivity for both receptors in the basal and often also suprabasal layer
      of normal and non-lesional psoriatic epidermis. In contrast, all psoriatic
      lesions studied lacked detectable immunoreactivity of either receptor in the
      epidermis. The results suggest that lack of TGF-beta-mediated growth inhibition
      by down-regulation of TGF-beta receptor expression may play an important part in
      the pathogenesis of psoriasis.

PMID- 9536225
TI  - Internalization of the 180 kDa bullous pemphigoid antigen as immune complexes in
      basal keratinocytes: an important early event in blister formation in bullous
      pemphigoid.
AB  - We have previously shown that the 180 kDa bullous pemphigoid antigen (BPAG2) is
      distributed on the lateral-apical (as a pool) and ventral (as hemidesmosomes)
      cell membranes of monolayer cultured keratinocytes and that addition of IgG
      purified from bullous pemphigoid (BP) patients (BP-IgG) causes the
      internalization of immune complexes of BPAG2 and BP-IgG from the lateral-apical
      cell membrane. This internalization of BPAG2 is believed to inhibit the Ca2+
      induced reformation of hemidesmosomes on the ventral cell membrane, possibly by
      inhibiting the supply of the antigen from the lateral-apical to the ventral
      membranes to form hemidesmosomes. The purpose of this paper is to examine, by
      using biopsy specimens from BP patients (12 cases), whether or not this
      internalization of BPAG2 is generated in situ. The fates of BPAG2, 230 kDa BPA
      (BPAG1) and bound BP-IgG were traced by immunofluorescence microscopy using
      monoclonal antibodies to BPAG1, BPAG2 and human IgG. In more than half of the
      lesional and perilesional biopsy specimens, internalization of BPAG2 into the
      basal cells was observed, while in normal skin BPAG2 was detected on the whole
      surface of the basal cells without its internalization. No internalization of
      BPAG1 was detected in BP and normal epidermis. These results suggest that binding
      of BP-IgG on the lateral-apical cell surface of basal cells causes
      internalization of BPAG2 in situ in the epidermis of BP patients similar to that
      seen in cultured cell systems, and that this internalization of immune complexes
      of BPAG2 and BP-IgG may play an important part in blister formation in BP.

PMID- 9536224
TI  - RANTES expression in psoriatic skin, and regulation of RANTES and IL-8 production
      in cultured epidermal keratinocytes by active vitamin D3 (tacalcitol).
AB  - The chemokine RANTES is a chemoattractant for eosinophils, T lymphocytes of
      memory phenotype and monocytes, suggesting that it plays an important part in
      chronic inflammatory and allergic diseases. In various types of cells, RANTES
      production is markedly induced by tumour necrosis factor (TNF)-alpha and
      interferon (IFN)-gamma in combination. Psoriasis vulgaris is a chronic cutaneous
      inflammatory disease. Cytokines and chemokines produced by T cells and epidermal
      keratinocytes, such as interleukin (IL) 8, are involved in the pathogenesis of
      psoriasis. T-cell clones obtained from psoriatic skin have been shown to produce
      the Th1 cytokine IFN-gamma. In addition, abnormal expression of proinflammatory
      cytokines including TNF-alpha has been observed in psoriatic lesions. These
      reports led us to hypothesis that psoriatic skin could provide epidermal
      keratinocytes with TNF-alpha and IFN-gamma, so that keratinocytes could produce
      RANTES. In this study, we addressed the question as to whether RANTES was
      involved in psoriasis vulgaris. Immunohistochemistry of skin biopsies showed
      RANTES was present in the intercellular spaces between epidermal keratinocytes,
      in the fully developed lesions from the middle to the edge of psoriatic plaques,
      but not in the perilesional uninvolved and healthy control skin. Further, we
      confirmed the production of RANTES, together with IL-8, by cultured normal human
      epidermal keratinocytes, using an enzyme-linked immunosorbent assay. Stimulation
      with TNF-alpha and IFN-gamma in combination synergistically increased the RANTES
      production in this system. These results clearly demonstrate the expression of
      RANTES in psoriatic lesions and suggest the involvement of this chemokine in the
      outcome of cutaneous inflammatory diseases. Tacalcitol (1 alpha,24(R)
      dihydroxyvitamin D3), an active vitamin D3 analogue, inhibited RANTES and IL-8
      production in cultured normal epidermal keratinocytes. This result indicates that
      active vitamin D3 is effective in the regulation of chemokine production by
      epidermal keratinocytes, which may partly account for its action as an
      antipsoriatic drug.

PMID- 9536226
TI  - Calcipotriene-induced improvement in psoriasis is associated with reduced
      interleukin-8 and increased interleukin-10 levels within lesions.
AB  - Calcipotriene is a synthetic analogue of 1,25-dihydroxyvitamin D3 established to
      be effective topically in the treatment of psoriasis. We investigated the early
      cellular and immunological events induced by calcipotriene in psoriasis. Thirty
      patients with moderate plaque-type psoriasis were randomly assigned to receive
      twice daily applications of either calcipotriene ointment 0.005% or matching
      vehicle for 6 weeks. Skin biopsies (6 mm) were performed from designated plaques
      at baseline and days 3 and 7. On these days and at weeks 2, 4 and 6, complete
      clinical evaluations were made in a double-blind fashion. Consistent with
      previous studies, significant clinical improvement (P < 0.05) in psoriasis was
      observed in patients receiving calcipotriene vs. those receiving vehicle by day 7
      for scale and erythema, and by day 14 for thickness. No significant improvement,
      however, was seen on day 3. None of the immunohistological markers (CD1a, CD4,
      CD8, ICAM-1, VCAM-1, E-selectin, HLA-DR) semiquantitatively assessed in psoriatic
      plaques was significantly changed by calcipotriene treatment for 7 days. In the
      calcipotriene-treated group, interleukin (IL)-10 levels (pg/microgram of protein)
      increased by 57% from baseline (0.030 +/- 0.006; mean +/- SEM) to day 3 (0.047 +/
      0.011) (P = 0.05 vs. baseline; n = 10) and remained elevated at day 7 (0.046 +/-
      0.012). IL-8 levels (pg/microgram of protein), however, declined by 70% from
      baseline (0.13 +/- 0.06) to day 3 (0.04 +/- 0.01), and remained low at day 7
      (0.03 +/- 0.02) (P < 0.05 vs. baseline; n = 10). Both IL-8 and IL-10 were
      unaffected by vehicle treatment. Calcipotriene-induced clinical improvement of
      psoriasis is preceded by an increase in IL-10 and a concomitant decrease in IL-8
      levels. The changes in the level of these two cytokines provide further evidence
      for immunological changes as a significant part of the mechanism of action of
      calcipotriene in psoriasis.

PMID- 9536227
TI  - The effect of addition of calcipotriol ointment (50 micrograms/g) to acitretin
      therapy in psoriasis.
AB  - Our purpose was to find out whether the addition of calcipotriol ointment (50
      micrograms/g) to systemic treatment with acitretin produces additional
      therapeutic effects and thereby an acitretin-sparing effect, and further to
      investigate the safety and tolerability of this combination. A multicentre,
      randomized, double-blind placebo-controlled study was designed. Patients were
      randomized to receive calcipotriol or placebo. All patients were treated with a
      starting dose of 20 mg acitretin per day and doses were adjusted at 2-weekly
      intervals with increments of 10 mg per day up to a maximum of 70 mg per day. The
      dose requirement for acitretin, clinical signs and adverse events were recorded.
      Seventy-six patients were randomized to treatment with calcipotriol 50
      micrograms/g ointment twice daily and 59 patients to treatment with the vehicle
      only twice daily. Clearance or marked improvement was achieved by 67% of the
      patients in the calcipotriol group and by 41% of the patients in the placebo
      group (P = 0.006). Calcipotriol treatment proved to have a statistically
      significant additional effect to acitretin on the Psoriasis Area and Severity
      Index, redness, thickness and scaliness as compared with placebo. Clearance or
      marked improvement was achieved with a statistically significantly lower
      cumulative dose of acitretin by the patients in the calcipotriol group as
      compared with the placebo group. The number of patients reporting adverse events
      was pronounced and largely related to acitretin. No significant differences were
      observed between the two treatment groups with respect to adverse events.
      Laboratory assessments were essentially normal. The addition of calcipotriol
      ointment to acitretin treatment contributes to the efficacy, reduces the
      cumulative dose of acitretin to reach marked improvement or clearance, and is
      well-tolerated and safe.

PMID- 9536228
TI  - A simplified protocol of steroid injection for psoriatic nail dystrophy.
AB  - Subjects seeking therapy for psoriatic nail dystrophy were recruited from routine
      clinics and involved digits were scored between 0 and 3 for severity of each of
      five features: subungual hyperkeratosis, pitting, onycholysis, ridging and
      thickening. These features were re-scored 2 months after injection of
      triamcinolone acetonide (0.4 mL, 10 mg/mL) into the nail bed and matrix following
      ring block, and then at 3-monthly intervals. A second injection was offered at 2
      months if warranted by poor response. Forty-six digits were injected in 19
      subjects (12 women, 7 men, mean age 48 years) receiving a mean of 1.2 doses.
      Follow-up ranged from 3 to 17 months (mean 9.4). Results are given for responses
      sustained up until the last follow-up. Onycholysis was present in 36 digits (78%)
      and improved in 18 (50%) of these. Pitting was present in 20 (43%), improving in
      nine (45%) and remaining unchanged in 11 (55%). Subungual hyperkeratosis was
      present in 16 (35%) and always improved after injection. Ridging was also present
      in 16 (35%) and improved in all but one instance. Thickening was present in 12
      cases (26%), improving in 10 (83%) and remaining unchanged in the rest. Although
      onycholysis and pitting are the most common elements of psoriatic dystrophy we
      show that they are the least responsive to steroid injected in this fashion.
      However, subungual hyperkeratosis, ridging and thickening respond well, with
      benefit sustained for at least 9 months. When these are the dominant features of
      a nail dystrophy, treatment according to the protocol in this study appears
      justified.

PMID- 9536229
TI  - Comparison of phototherapy with near vs. far erythemogenic doses of narrow-band
      ultraviolet B in patients with psoriasis.
AB  - The therapeutic effectiveness of radiation from a 311 nm ultraviolet B (UVB) lamp
      (Philips TL-01) in a near vs. far erythemogenic therapy regimen was investigated
      in 13 patients with widespread, symmetrically distributed psoriasis. The patients
      received UV therapy starting with 70% of the 311 nm minimal erythema dose (MED)
      on one randomly chosen half of the body and 35% of the 311 nm MED on the other
      half. Therapy was given three to five times a week, and the UVB dose in both
      regimens was increased simultaneously in the same relation. For the 11 patients
      completing the study, the mean psoriasis area and severity index (PASI) score for
      the near vs. far erythemogenic treatment side was 21.2 vs. 18.5 before therapy
      (Wilcoxon's test, not significant), 11.8 vs. 14.4 at week 1 (P = 0.003), 8.2 vs.
      12.0 at week 2 (P = 0.004), and 6.6 vs. 15.6 at week 3 (P = 0.005). After 3
      weeks, a satisfactory response (i.e. improvement of the initial PASI score by
      more than 75%) was observed in six of 11 patients on the near erythemogenic
      treatment side vs. three of 11 patients on the far erythemogenic side. However,
      the definitive median total number of treatments needed to achieve a satisfactory
      therapy response on the near vs. far erythemogenic sides was 12 vs. 16 (P =
      0.022), whereas the definitive median cumulative UV dose was 14.0 vs. 9.1 J/cm2
      (P = 0.088), respectively. These results suggest that near erythemogenic 311 nm
      UVB therapy may clear psoriasis faster than far erythemogenic therapy but that
      the latter regimen may be equally effective as it requires slightly more
      treatment sessions at a lower (and possibly less carcinogenic) cumulative UV
      dose.

PMID- 9536230
TI  - Intravenous immunoglobulin in autoimmune chronic urticaria.
AB  - Histamine releasing autoantibodies play a central role in the pathogenesis of
      chronic urticaria (CU) in approximately 30% of affected patients. We investigated
      the therapeutic effect of high-dose intravenous immunoglobulin (IVIG) on disease
      activity in patients with severe CU of autoimmune aetiology. Autoimmune urticaria
      was diagnosed by the development of a weal-and-flare reaction to the intradermal
      injection of autologous serum and by serum-induced histamine release from the
      basophil leucocytes of healthy donors in vitro. Ten patients with severe,
      autoimmune CU, poorly responsive to conventional treatment, were treated with
      IVIG 0.4 g/kg per day for 5 days. The outcome on cutaneous wealing and itch was
      monitored using urticaria activity scores, visual analogue scales and autologous
      intradermal serum tests. Clinical benefit was noted in nine of 10 patients: three
      patients continue in prolonged complete remissions (3 years follow-up), two had
      temporary complete remissions, and symptoms in four patients improved subsequent
      to treatment. There was significant improvement in the urticaria activity scores
      and visual analogue scores at 2 (P < 0.01) and 6 weeks (P < 0.01) post-IVIG
      compared with the baseline values (Wilcoxon matched pairs). The diminution in
      urticarial activity in the majority of patients corresponded with a reduced weal
      and-flare response to the intradermal injection of autologous post-treatment
      serum compared with the pretreatment serum. Minor side-effects were common, but
      there were no serious or long-term adverse effects. IVIG represents a novel
      therapeutic option in selected patients with recalcitrant CU associated with
      histamine releasing autoantibodies.

PMID- 9536231
TI  - The family impact of childhood atopic dermatitis: the Dermatitis Family Impact
      Questionnaire.
AB  - Little information is available about the effect of childhood atopic dermatitis
      (AD) on family function. The aim of this study was to identify the areas of
      family life most affected and their perceived importance. Intensive qualitative
      interviews with 34 families were conducted and 11 basic problem areas were
      identified. A detailed questionnaire was prepared, part of which addressed the
      perceived importance of particular issues using the framework of multi-attribute
      utility theory. The results from using this questionnaire in 41 families were
      analysed and a shorter 10-question one-page Dermatitis Family Impact (DFI)
      questionnaire designed (maximum score = 30). In affected families the mean DFI
      score was 9.6 +/- 7.0 (range 0-27, n = 56) and in unaffected families the mean
      score was 0.4 +/- 0.9 (range 0-3, n = 26, P < 0.0001). The DFI could potentially
      be used as an extra measure in clinical studies, or to help guide appropriate
      management of AD.

PMID- 9536232
TI  - Counterimmunoelectrophoresis, ELISA and immunoblotting detection of anti-Ro/SSA
      antibodies in subacute cutaneous lupus erythematosus. A comparative study.
AB  - Patients with subacute cutaneous lupus erythematosus (SCLE) have circulating
      antibodies to Ro/SSA directed to two antigenically distinct ribonucleoproteins of
      60 kDa and 52 kDa. Three laboratory tests may be used to detect anti-Ro/SSA
      antibodies: counterimmunoelectrophoresis (CIE), enzyme-linked immunosorbent assay
      (ELISA) and immunoblotting (IB). Their relative efficacy and clinical
      correlations were ascertained. We determined anti-Ro/SSA antibodies with CIE,
      with two different ELISA methods (ELISA 1 and 2) and with IB in 29 SCLE patients.
      Anti-52 kDa and -60 kDa Ro/SSA antibodies were also assayed with IB. In addition,
      we determined antinuclear antibodies with indirect immunofluorescence, anti-Sm,
      anti-RNP, anti-La/SSB and anti-Ro/SSA antibodies with CIE and ELISA, and anti
      nDNA and cardiolipin antibodies using an ELISA method. CIE detected anti-Ro/SSA
      antibodies in 22 patients while ELISA 1 and 2 did so in 17 and 18 patients,
      respectively. In five patients, IB revealed a reactivity to 60 kDa polypeptides
      and in two, a reactivity to 52 kDa polypeptides. Of these seven patients, four
      had a myocardial infarction. Of these, two reacted to the 52 kDa antigen and two
      to the 60 kDa antigen. A combination of techniques was often needed to detect all
      specificities. ELISA proved to be very specific and sensitive. The IB technique
      detected a group of patients with myocardial infarction. A case-control study is
      needed to confirm the data of cardiac involvement.

PMID- 9536233
TI  - Opposite effects of tumour necrosis factor-alpha on type I and III collagen gene
      expression by human dermal fibroblasts in monolayer and three-dimensional
      cultures.
AB  - We have recently established a novel fibroblast culture system supplemented with
      L-ascorbic acid 2-phosphate. The addition of L-ascorbic acid 2-phosphate enables
      human dermal fibroblasts to organize a three-dimensional dermis-like structure by
      accumulating collagens and extracellular matrices. The purpose of this study was
      to examine the effects of tumour necrosis factor-alpha (TNF-alpha) on collagen
      gene expression by human dermal fibroblasts in this culture system in comparison
      with monolayer culture. TNF-alpha suppressed the expression of pro alpha 1 (I)
      and pro alpha 1 (III) collagen mRNA in monolayer culture. In contrast, their
      expression was elevated in the three-dimensional culture system. TNF-alpha
      increased the mRNA expression of matrix metalloproteinase-1 and tissue inhibitor
      of metalloproteinase-1 both in monolayer and three-dimensional culture. These
      data suggest that responses of human dermal fibroblasts to TNF-alpha are distinct
      under the different culture conditions. Extracellular matrices may modulate the
      responsiveness of fibroblasts to TNF-alpha.

PMID- 9536234
TI  - Cutaneous malignant melanoma in women and the role of oral contraceptives.
AB  - The role of oral contraceptives (OC) in the aetiology of cutaneous malignant
      melanoma (CMM) has been controversially discussed over the last two decades. In
      an extensive literature search we identified 18 case-control studies, published
      between 1977 and 1996, offering information on this relationship. Using a meta
      analytical approach we combined the study-specific risk estimates and derived a
      summary odds ratio of 0.95 (95% confidence interval: 0.87-1.04). Based on the
      data of 3796 cases and 9442 controls, we thus found no evidence for an
      aetiological role of OC use in the development of CMM.

PMID- 9536235
TI  - Acquired junctional epidermolysis bullosa associated with IgG autoantibodies to
      the beta subunit of laminin-5.
AB  - We report the case of a 72-year-old man with clinical features resembling those
      of non-lethal junctional epidermolysis bullosa associated with IgG autoantibodies
      to the beta chain of laminin-5. The patient presented with a sudden onset of
      blistering and severe fragility of the skin and mucous membranes resulting in
      atrophic scars. Electron microscopy showed that the blistering arose in the
      lamina lucida. Indirect immunofluorescence indicated that the autoantibodies
      bound to the dermal side of 1 mol/L NaCl-split skin, and both direct and indirect
      immunoelectron microscopy demonstrated antibody binding to the lamina densa.
      Postembedding immunogold electron microscopy also revealed labelling in the
      lamina lucida beneath the hemidesmosomes. On immunoblotting, we found the
      autoantibodies to comigrate with the beta chain of laminin-5. Following the
      nomenclature of inherited junctional epidermolysis bullosa with mutations of the
      laminin-5 gene, we propose the name acquired junctional epidermolysis bullosa for
      this newly recognized disease.

PMID- 9536236
TI  - Assignment of three Chinese xeroderma pigmentosum patients to complementation
      group C and one to group E.
AB  - Four Chinese patients with xeroderma pigmentosum (XP), who had different degrees
      of skin symptoms, were tested for their genetic complementation groups. Skin
      fibroblasts obtained from the patients were used for complementation analysis
      done by a cell-fusion technique. Three of the patients belonged to group C and
      one, who had the mildest cutaneous manifestations, to group E. This is the first
      report of a group E XP patient in China. Our present findings together with
      previous reports suggest that group C XP is more common in China, similar to the
      distribution among Caucasian XP patients but markedly different from the Japanese
      distribution.

PMID- 9536237
TI  - Prurigo as a clinical prodrome to adult T-cell leukaemia/lymphoma.
AB  - We report a case of adult T-cell leukaemia/lymphoma (ATLL) with prurigo as a
      prodromal skin manifestation. The patient was a 52-year-old woman with a 2-year
      history of a fluctuating skin condition consisting of pruritic papules and
      pigmentation on her lower legs and right buttock. Prurigo was diagnosed at her
      first visit in October 1995, and she was found to be seropositive for human T
      cell lymphotropic virus type 1 (HTLV-1). Two years later, the skin lesions had
      spread over the patient's forearms and dorsa of the hands, and abnormal lymphoid
      cells had appeared in her peripheral blood. Southern blot analysis revealed
      monoclonal integration of HTLV-1 provirus in the peripheral blood, but not in a
      skin lesion. Based on these results, a diagnosis of overt ATLL of the smouldering
      type was made. The findings in this case indicate that in healthy HTLV-1
      seropositive carriers, prurigo requires careful follow-up as a cutaneous prodrome
      of ATLL.

PMID- 9536238
TI  - Vesicular mycosis fungoides.
AB  - Blistering is not a feature normally associated with mycosis fungoides (MF). We
      present a case of MF in which histopathological vesicle formation was such a
      prominent feature that diagnosis was delayed. The patient's disease ran an
      aggressive course and death occurred within one year of presentation. Tumour
      involvement of the tongue with MF was an unusual late feature.

PMID- 9536239
TI  - Cutaneous metastasis from a presumed signet-ring cell carcinoma in a 10-year-old
      child.
AB  - Cutaneous metastases of internal malignancies are very rare in children. In this
      group, neuroblastoma, leukaemia and lymphoma are the most common malignancies
      that may develop metastases or neoplastic infiltrates to the skin. Carcinomas
      have infrequently been reported in children, and cutaneous metastases from
      carcinoma in this group have not been described. A 10-year-old girl presented
      with an erythematous plaque on the left hemithorax. Histopathological findings
      revealed grouped signet-ring cells within the lumina of lymphatic vessels in the
      dermis. Immunohistochemical examination confirmed the epithelial origin of the
      tumour. Despite an exhaustive search, the primary site could not be determined.
      This exceptional observation is, to the best of our knowledge, the first report
      of cutaneous metastasis from occult carcinoma in a child.

PMID- 9536240
TI  - Steatocystoma multiplex and leuconychia in a child with Alagille syndrome.
AB  - Alagille syndrome is a rare autosomal dominant developmental disorder,
      characterized by congenital paucity of interlobular bile ducts, peculiar facies,
      posterior embryotoxon, bone abnormalities, and peripheral pulmonary artery
      stenosis. Cutaneous involvement in this disorder is quite rare and the
      association of Alagille syndrome with multiple comedones and cysts has been
      described only once. Here, we report the clinical and histological findings of a
      7-year-old patient affected by Alagille syndrome who presented multiple cystic
      lesions and comedones reminiscent of steatocystoma multiplex and a congenital
      total true leuconychia. Although unexplained, the association of this syndrome
      with a developmental disorder of the pilosebaceous unit may not be fortuitous.

PMID- 9536241
TI  - Cutaneous reactions at sites of herpes zoster scars: an expanded spectrum.
AB  - Several types of cutaneous lesions have previously been described at the sites of
      herpes zoster scars. We describe 16 patients with cutaneous lesions which had
      developed on herpes zoster scars. Biopsies were taken from these lesions, and a
      polymerase chain reaction assay was used to detect the viral genome in paraffin
      embedded specimens. Histopathological findings enabled diagnosis of nonspecific
      granulomatous dermatitis in five patients, granulomatous vasculitis in two
      patients, lichen sclerosus in two patients, and pseudolymphoma, keloid, sarcoidal
      granuloma, granuloma annulare, granulomatous folliculitis, lichen planus and
      cutaneous Rosai-Dorfman disease, each in one patient. Varicella-zoster virus DNA
      was not identified in any of the patients. Granulomatous folliculitis, lichen
      sclerosus and cutaneous Rosai-Dorfman disease have not previously been described
      in herpes zoster scars, but they are three new cutaneous reaction patterns that
      may have developed within these scars. Our investigations indicate that the
      cutaneous reactions appearing in herpes zoster scars are not due to the
      persistence of varicella-zoster virus DNA within the lesions.

PMID- 9536242
TI  - Carbon dioxide laser treatment of extramammary Paget's disease guided by
      photodynamic diagnosis.
AB  - Extramammary Paget's disease (EPD) is a rare malignancy occurring mainly in
      apocrine gland-bearing regions. Surgical excision is the treatment of choice.
      This may be very difficult or even impossible if the disease is widespread or
      located in a critical anatomical site. We report on the successful treatment of a
      71-year-old man with EPD in the suprapubic region with CO2 laser guided by
      photodynamic diagnosis.

PMID- 9536243
TI  - Dietary fish oil as a photoprotective agent in hydroa vacciniforme.
AB  - Hydroa vacciniforme is a troublesome and scarring photosensitivity disorder for
      which treatment is unsatisfactory. Dietary fish oil rich in omega-3
      polyunsaturated fatty acids reportedly increases the resistance to ultraviolet
      induced erythema and rash provocation in polymorphic light eruption. We report
      for the first time the response of hydroa vacciniforme to dietary fish oil. Three
      Caucasian boys with the condition were placed on MaxEPA, five capsules daily.
      Phototesting was performed at baseline and after 3 months supplementation. At
      baseline, low erythemal thresholds were seen to monochromated UVA at 350 and 370
      nm in all three boys, while one also had a low threshold to 320 nm (UVA) and
      another showed a low threshold to 300 nm (UVB). Broad-band UVA provocation
      challenge produced typical skin lesions in all the subjects. Following fish oil,
      all the boys showed reduced erythemal sensitivity to UVA and one also showed
      reduced sensitivity to UVB. Provocation challenge revealed a reduced response in
      all three children. Clinically, these changes were accompanied by pronounced
      improvement in one child, mild improvement in the second child, but no
      improvement in the third. The third boy subsequently showed good clinical
      response to azathioprine.

PMID- 9536244
TI  - Psoriasis vulgaris treated successfully with mycophenolate mofetil.
AB  - Mycophenolate mofetil (MMF) is a new immunosuppressive drug which non
      competitively and reversibly blocks the de novo synthesis of guanine nucleotides
      required for DNA and RNA synthesis during T- and B-cell proliferation. This
      induces a selective inhibition of lymphocyte proliferation. Thus MMF is currently
      used to prolong graft survival in renal transplant patients. In this
      communication we describe the first case of a man with severe psoriasis treated
      successfully with oral MMF without short-term side-effects. The psoriasis area
      and severity index score decreased during therapy (5 weeks) from 22.0 to 11.4.
      Thus MMF appears to be an effective therapeutic alternative in the treatment of
      severe psoriasis.

PMID- 9536246
TI  - The detection of human papillomavirus 16 DNA in erythroplasia of Queyrat invading
      the urethra.

PMID- 9536245
TI  - Association of atopic dermatitis to the beta subunit of the high affinity
      immunoglobulin E receptor.
AB  - IgE dysregulation is a major pathogenic feature of atopic dermatitis and other
      IgE-mediated allergic diseases such as asthma and rhinitis. Allergen complexed to
      IgE binds to the high affinity receptor for IgE (Fc epsilon RI) on the surface of
      epidermal Langerhans cells, mast cells and basophils, triggering the release of
      inflammatory mediators. The beta subunit of Fc epsilon RI has been localized to
      human chromosome 11q12-13, and variants within this gene have been shown to
      associate with asthma and measures of atopy. We have tested several polymorphisms
      within Fc epsilon RI-beta for association to atopic dermatitis in a panel of 60
      families (panel A), recruited through a proband with atopic dermatitis. The
      findings were tested in a second panel of families (panel B). Significant sharing
      of maternal alleles was seen for atopic dermatitis and allele 2 of RsaI intron 2
      (RsaIvin2*2) (P = 0.0022) and allele 1 of RsaI exon 7 (RsaIvex7*1) (P = 0.0036)
      Fc epsilon RI-beta gene polymorphisms. These findings were replicated in Panel B,
      confirming the association of Fc epsilon RI-beta RsaI polymorphisms with atopic
      dermatitis. The combined significance of the association of atopic dermatitis to
      RsaI polymorphisms was P = 0.0002 (RsaIvin2*2) and P = 0.00034 (RsaIvex7*1). The
      polymorphisms also showed association with asthma: P = 0.0068 (RsaIvin2*2) and P
      = 0.018 (RsaIvex7*1). Polymorphisms within the Fc epsilon RI-beta gene are
      strongly associated with atopic dermatitis.

PMID- 9536247
TI  - Subungual dermatophytoma complicating dermatophyte onychomycosis.

PMID- 9536248
TI  - Mucosal leishmaniasis in a heart transplant recipient.

PMID- 9536249
TI  - Crusted scabies with scalp involvement in HIV-1 infection.

PMID- 9536250
TI  - Red fingers syndrome in a HIV-negative woman with hepatitis C cirrhosis.

PMID- 9536251
TI  - Urticaria and hepatitis C infection.

PMID- 9536252
TI  - Epidermal-binding circulating antibodies in epidermolysis bullosa acquisita: what
      are they?

PMID- 9536253
TI  - Paraneoplastic pemphigus associated with Hodgkin's disease.

PMID- 9536254
TI  - The use of azithromycin for cyclosporin-induced gingival overgrowth.

PMID- 9536255
TI  - Lupoid sycosis successfully treated with minocycline.

PMID- 9536256
TI  - The Koebner phenomenon in vitiligo following treatment of a port-wine stain
      naevus by pulsed dye laser.

PMID- 9536257
TI  - PUVA therapy for disabling pansclerotic morphoea of children.

PMID- 9536258
TI  - Early diagnosis of malignant melanoma: surgical excision of 37 moles.

PMID- 9536259
TI  - Gene therapy in the developing world.

PMID- 9536260
TI  - Leptin gene therapy and daily protein administration: a comparative study in the
      ob/ob mouse.
AB  - We have compared the efficacy of daily injection of recombinant leptin protein
      (rh-leptin) with adenovirus-mediated delivery of the murine or human leptin gene
      (Ad-leptin) for treatment of obesity in the obese (ob/ob) mouse model. We
      demonstrate an improved correction profile for obesity and associated surrogate
      markers using the adenovirus delivery method. Rate of weight loss and percentage
      satiety were significantly greater in the mice treated with Adleptin. These
      findings were associated with lower peak serum leptin levels with Ad-leptin (22.9
      +/- 2.6 ng/ml for the human gene, and 48.9 +/- 11.5 ng/ml for the murine gene)
      compared to rh-leptin (385.2 +/- 36.0 ng/ml). (Values are given as mean +/-
      standard error of the mean.) Importantly rh-leptin and ex vivo-expressed Ad
      leptin were equivalently active in a functional cell-based assay. The primary
      difference in the two therapeutic approaches is the continuous chronic secretion
      of leptin mediated by gene delivery, versus the intermittent bolus delivery and
      rapid clearance of the daily injection of rh-leptin protein. Thus, in vivo
      findings suggest that leptin effects are better achieved at lower steady-state
      levels, a pharmacological feature attained here by gene therapy. These findings
      may have implications for the potential use of leptin in the treatment of
      obesity.

PMID- 9536262
TI  - Increase of proliferation rate and enhancement of antitumor cytotoxicity of
      expanded human CD3+ CD56+ immunologic effector cells by receptor-mediated
      transfection with the interleukin-7 gene.
AB  - Cytokine-induced killer (CIK) cells have been shown to eradicate established
      tumors in a SCID mouse-human lymphoma model. CIK cells depend on exogenous
      addition of cytokines such as interleukin-2 (IL-2), interleukin-7 (IL-7) or
      interleukin-12 (IL-12) for proliferation. In this study, we used the adenovirus
      enhanced CD3 receptor-mediated gene transfer for transfection with the IL-7 gene.
      An episomally replicating plasmid was used containing cDNA of the human IL-7 gene
      under the control of a CMV promoter for transfection of CIK cells. Biosynthesis
      of IL-7 was demonstrated by RT-PCR, an enzyme-linked immunosorbent assay (ELISA)
      and using a bioassay. Transfected cells produced IL-7 in the range between 200
      and 1100 pg/10(6) cells in 24 h. IL-7 was shown to be biologically active, since
      transfected CIK cells showed an improved proliferation rate as compared with
      nontransfected cells. Expression of IL-7 altered the secretion of other cytokines
      by CIK cells, in particular the production of TNF alpha increased after
      transfection. In contrast, nontransfected CIK cells fed with IL-7 showed no
      increase in TNF alpha secretion. No significant differences were found in
      expression of surface antigens linked to the cytotoxic activity of CIK cells.
      Cytotoxic activity against various tumor cell lines (eg renal cell carcinoma,
      malignant melanoma and colon carcinoma) was tested. Transfected cells possessed a
      significantly higher cytotoxic activity as compared with nontransfected cells.
      Receptor-mediated gene transfer effectively delivers expression plasmids for
      therapeutic genes into CIK cells and CIK cells transfected with an IL-7 gene
      expression construct may be valuable for adoptive immunotherapy.

PMID- 9536261
TI  - Ex vivo gene transfer using adenovirus-mediated full-length dystrophin delivery
      to dystrophic muscles.
AB  - Duchenne muscular dystrophy (DMD) is an X-linked recessive muscle disease
      characterized by a lack of dystrophin expression. Myoblast transplantation and
      gene therapy have the potential of restoring dystrophin, thus decreasing the
      muscle weakness associated with this disease. In this study we present data on
      the myoblast mediated ex vivo gene transfer of full-length dystrophin to mdx
      (dystrophin deficient) mouse muscle as a model for autologous myoblast transfer.
      Both isogenic primary mdx myoblasts and an immortalized mdx cell line were
      transduced with an adenoviral vector that has all viral coding sequences deleted
      and encodes beta-galactosidase and full-length dystrophin. Subsequently, these
      transduced myoblasts were injected into dystrophic mdx muscle, where the injected
      cells restored dystrophin, as well as dystrophin-associated proteins. A greater
      amount of dystrophin replacement occurred in mdx muscle following transplantation
      of mdx myoblasts isolated from a transgenic mouse overexpressing dystrophin
      suggesting that engineering autologous myoblasts to express high amounts of
      dystrophin might be beneficial. The ex vivo approach possesses attributes that
      make it useful for gene transfer to skeletal muscle including: (1) creating a
      reservoir of myoblasts capable of regenerating and restoring dystrophin to
      dystrophic muscle; and (2) achieving a higher level of gene transfer to
      dystrophic muscle compared with adenovirus-mediated direct gene delivery.
      However, as observed in direct gene transfer studies, the ex vivo approach also
      triggers a cellular immune response which limits the duration of trans-gene
      expression.

PMID- 9536263
TI  - Direct intramuscular injection with recombinant AAV vectors results in sustained
      expression in a dog model of hemophilia.
AB  - A recombinant adeno-associated virus (rAAV) vector carrying the human factor IX
      cDNA was tested for safety and therapeutic gene expression in a canine model of
      human hemophilia B. Intramuscular delivery of rAAV was chosen based on our
      previous work which described long-term (> 1.5 years) reporter gene expression in
      immunocompetent mice following direct muscle injection. For the current study,
      rAAV with the human factor IX (hF.IX) cDNA under the control of the
      cytomegalovirus (CMV) immediate-early promoter was constructed, and rAAV/hF.IX
      proved capable of transducing hemophilic dog primary fibroblast cultures in a
      dose-dependent fashion. Direct intramuscular injection of 2.5 x 10(12) rAAV/hF.IX
      virus particles into the hindlimbs of a hemophilia B dog was tolerated without
      bleeding or systemic reaction, and the animal was asymptomatic throughout the
      entire study. Transient reduction in the whole blood clotting time (WBCT)
      occurred during the first week, with the anticipated development of an antihuman
      F.IX inhibitor antibody which corresponded with the loss of coagulation
      correction. At 10 weeks after vector administration, immunohistochemical analysis
      of injected muscle confirmed continued hF.IX expression. Limited areas of focal
      lymphocytic infiltration and myofiber pathology were detected which directly
      correlated with positive antibody staining for helper adenovirus contamination.
      PCR tissue analysis revealed rAAV/hF.IX DNA solely in injected muscle tissue and
      adjacent lymph node, without dissemination to other organs (including gonads).
      This first large animal study suggests that intramuscular gene delivery using
      rAAV vectors is safe and supports continued development of this approach for gene
      therapy of human diseases, including hemophilia B.

PMID- 9536264
TI  - Gene transfer and expression in oligodendrocytes under the control of myelin
      basic protein transcriptional control region mediated by adeno-associated virus.
AB  - In this study, a rAAV vector carrying a reporter gene, 'humanized' green
      fluorescent protein (GFP), linked to the transcriptional control region from the
      myelin basic protein (MBP) gene (a myelin-forming cell-specific gene) was
      constructed. Transduction of oligodendrocytes was carried out both in vitro and
      in vivo. The GFP expression was detected for at least 3 weeks in both transduced
      oligodendrocyte cell line (MOCH-1 cells) and primary cultures of rat
      oligodendrocytes. Preferential GFP expression in oligodendrocytes was observed in
      the primary cultures. In contrast, transduction with rAAV carrying the CMV
      promoter produced stronger GFP fluorescence in various cell types, with the
      majority of GFP-expressing cells being the astrocytes. Infusion of approximately
      6 x 10(9) particles (2 x 10(5) infectious units) of rAAV-MBP-GFP into mouse
      brains resulted in the GFP expression specifically in white matter. The GFP
      protein was detected 15 days later by immunostaining, specifically in the
      oligodendrocytes. No astrocytes were transduced. Our studies suggested that cell
      types other than neurons in the central nervous system can also be transduced by
      rAAV using a cell-type-specific transcriptional control region or promoter. The
      MBP transcriptional control region might be suitable for gene therapy and other
      neurobiology studies requiring direct targeting to the myelinating cells.

PMID- 9536265
TI  - Mini- and full-length dystrophin gene transfer induces the recovery of nitric
      oxide synthase at the sarcolemma of mdx4cv skeletal muscle fibers.
AB  - In normal skeletal muscle fibers, dystrophin accumulates at the cytoplasmic face
      of the sarcolemma where it associates with dystrophin-associated proteins (DAPs).
      Several studies have recently shown that the neuronal isoform of nitric oxide
      synthase (nNOS) is also located at the sarcolemma, and that this membrane
      localization is mediated through interactions of nNOS with one of the DAPs,
      namely alpha 1-syntrophin. Since the lack of dystrophin in muscle fibers from
      Duchenne muscular dystrophy patients and mdx mice is accompanied by an absence of
      sarcolemmal nNOS, we examined in the present study, whether dystrophin gene
      replacement would lead to the restoration of nNOS at its appropriate subcellular
      location. To this end, tibialis anterior muscles from mdx4cv mice were directly
      injected with plasmid DNA encoding either full-length (pRSV-dys) or mini-(pRSV
      dyB; lacking exons 17-48) dystrophin. For these experiments, we chose to study 10
      week-old mdx4cv mice since at this developmental stage, muscles from these mice
      have already undergone several cycles of degeneration-regeneration.
      Immunofluorescence experiments performed on serial cross-sections revealed that
      approximately 50% of the dystrophin-positive fibers also exhibited significant
      levels of nNOS at their sarcolemma 2 weeks following gene transfer with pRSV-dys.
      Similar results were obtained with pRSV-dyB indicating that exons 17-48 of the
      dystrophin gene are not essential for the correct localization of nNOS in
      skeletal muscle fibers. Taken together with the recent demonstration that
      dystrophin gene transfer leads to significant physiological benefits our results
      suggest that dystrophin gene therapy using full-length or truncated dystrophin,
      also induces a rapid recovery of biochemical functions.

PMID- 9536266
TI  - Inhibition of HIV-1 replication by combined expression of gag dominant negative
      mutant and a human ribonuclease in a tightly controlled HIV-1 inducible vector.
AB  - An HIV-1-based expression vector has been constructed that produces protective
      genes tightly regulated by HIV-1 Tat and Rev proteins. The vector contains either
      a single protective gene (HIV-1 gag dominant negative mutant (delta-gag)) or a
      combination of two different protective genes (delta-gag and eosinophil-derived
      neurotoxin (EDN), a human ribonuclease) which are expressed from a dicistronic
      mRNA. After stable transfection of CEM T cells and following challenge with HIV
      1, viral production was completely inhibited in cells transduced with the vector
      producing both delta-gag and EDN and delayed in cells producing delta-gag alone.
      In addition, cotransfection of HeLa-Tat cells with an infectious HIV-1 molecular
      clone and either protective vector demonstrated that the HIV-1 packaging signals
      present in the constructs were functional and allowed the efficient assembly of
      the protective RNAs into HIV-1 virions, thus potentially transmitting protection
      to the HIV-1 target cells.

PMID- 9536267
TI  - Efficient transgene regulation from a single tetracycline-controlled positive
      feedback regulatory system.
AB  - Control of gene expression in eukaryotic cells is clearly important in many
      applications including modifications of the level of a therapeutic gene product.
      For effective gene delivery and regulation, the regulatory system must be
      contained on a single vector and it must exhibit high transgene expression on
      induction and low basal expression on repression. Here, we have investigated
      several self-contained vectors carrying both the tetracycline-controlled
      transactivator (tTA) and a potentially therapeutic gene in transient studies. An
      enhancerless positive feedback regulatory vector (pSiaIV) transcribing both tTA
      and mGM-CSF from a modified tTA-responsive bidirectional promoter demonstrated
      over 200-fold gene regulation in HeLa cells. This was comparable to the degree of
      regulation obtained on cotransfection of vectors expressing tTA and tTA
      responsive mGM-CSF. The maximal transcriptional activity of pSiaIV was comparable
      to that of CMV IE promoter and its basal activity as low as the leakiness of the
      tetracycline-responsive promoter (tRP) in several commonly used cell lines,
      resulting in 47- to 328-fold regulation. Furthermore, pSiaIV also showed
      efficient regulation in stable cells. Overall, the positive feedback regulatory
      system (PFRS) offers efficient gene regulation which is suitable for most
      applications, especially gene therapy.

PMID- 9536268
TI  - Transient immunosuppression with 15-deoxyspergualin prolongs reporter gene
      expression and reduces humoral immune response after adenoviral gene transfer.
AB  - A strong immune response against transgenic cells is one important limitation for
      long-term expression after adenoviral gene transfer in mammals. Continuous
      pharmacological immunosuppression has been shown to ameliorate immune reactions
      and to prolong reporter gene expression. In this study, we explored the effect of
      short-term immunosuppression for long-term gene expression and its impact on
      antibody formation. Immunosuppression with FK 506 (1 mg/kg/day), cyclosporin A
      (20 mg/kg/day) and 15-deoxyspergualin (10 mg/kg/day) was performed in NMRI mice.
      Expression of the reporter gene human alpha-1-antitrypsin (hAAT) and antibody
      formation was monitored for 7 months. A 5-day course of 15-deoxyspergualin (15
      DSG) markedly slowed the decline of reporter gene expression and a positive
      effect was still detectable 200 days after gene transfer. At the same time,
      antibody production was reduced by 50-60%. Continuous treatment with 15-DSG (10
      mg/kg twice weekly) led to a further small increase of gene expression but
      reduced antibody formation by 80-90%. A short course of FK 506 and cyclosporin A
      (CsA), had conferred a negative effect on gene expression. Both groups showed an
      even faster reduction in gene expression compared with the control group. The
      results of this investigation suggest that 15-DSG could serve as an effective
      supplement for viral gene therapy protocols.

PMID- 9536269
TI  - The effect of mucolytic agents on gene transfer across a CF sputum barrier in
      vitro.
AB  - Trials of gene transfer for cystic fibrosis (CF) are currently underway. However,
      direct application to the airways may be impeded by the presence of airway
      secretions. We have therefore assessed the effect of CF sputum on the expression
      of the reporter gene beta-galactosidase complexed with the cationic liposome DC
      Chol/DOPE in a number of cell lines in vitro. Transfection was markedly inhibited
      in the presence of sputum; the effect was concentration dependent and was only
      partially ameliorated by removal of sputum with phosphate-buffered saline (PBS)
      washing before gene transfer. However, treatment of the sputum-covered cells with
      recombinant human DNase (rhDNase, 50 micrograms/ml) but not with N
      acetylcysteine, Nacystelyn, lysine (all 20 mM) or recombinant alginase (0.5 U/ml)
      significantly (P < 0.005) improved gene transfer. Adenovirus-mediated gene
      transfer efficiency in the presence of sputum was similarly inhibited, and again,
      treatment with rhDNase before transfection significantly improved gene transfer
      (P < 0.005). Transfection of Cos 7 cells in the presence of exogenous genomic DNA
      alone demonstrated similar inhibition to that observed with sputum and was also
      ameliorated by pre-treatment of DNA-covered cells with rhDNase. In a separate
      series of experiments performed in the absence of added sputum or genomic DNA,
      increasing concentrations of rhDNase resulted in a concentration-related decline
      in transfection efficiency. However, even at the highest concentration (500
      micrograms/ml of rhDNase), transfection efficiency remained more than 50% of
      control. Thus, pre-treatment of CF airways with rhDNase may be appropriate before
      liposome or adenovirus-mediated gene therapy.

PMID- 9536270
TI  - Transduction of human macrophages using a stable HIV-1/HIV-2-derived gene
      delivery system.
AB  - We have previously established a stable HIV-1 packaging cell line, psi 422, which
      yielded high titers of an HIV-1 vector capable of efficiently transducing CD4+
      cells. In order to increase the safety of this gene delivery system, we have now
      replaced the HIV-1 vector with an HIV-2 vector to abolish any risk of homologous
      recombination between the packaging cells and the vector. The HIV-2 vector was
      also modified by insertion of a cis-acting constitutive transport element which
      confers Rev independence. The supernatant of psi 422 cells stably transfected
      with this new vector was capable of transducing CD4+ cells with a titer of 10(4)
      transducing units per milliliter. This result shows that cross-packaging of HIV-2
      vectors with the HIV-1 packaging cells is quite efficient. Using this new stable
      HIV-1/HIV-2 gene delivery system, we were able to transduce human monocyte
      derived primary macrophages, which are refractory to murine retrovirus-mediated
      transduction. The availability of a stable HIV-based gene delivery system for
      macrophages, a key target cell in HIV infection; is an important advance in gene
      therapy for AIDS.

PMID- 9536271
TI  - Gene-directed enzyme prodrug therapy: quantitative bystander cytotoxicity and DNA
      damage induced by CB1954 in cells expressing bacterial nitroreductase.
AB  - Clones of human colon carcinoma (WiDr), ovarian carcinoma (SK-OV-3), and Chinese
      hamster V79 cells expressing the nitroreductase enzyme (NR) from E. coli B were
      52-, 225- and 177-fold respectively more sensitive to a 24-h incubation with the
      prodrug 5-(aziridin-1-yl)-2,4-dinitrobenzamide (CB1954) than the parent lines.
      The IC50s of non-NR-expressing bystander cells were measured in the presence of
      differing proportions of NR-expressing cells. The shift in IC50 was used to
      calculate a value for the bystander effect, termed the transmission efficiency
      (TE), which is the decrease in IC50 due to bystander effect as a percentage of
      the maximum decrease possible. The percentage of NR-expressing cells for which
      the TE was 50%, (the TE50) is a single datum of bystander efficacy. WiDr and V79
      cell lines, had a similar TE50 of approximately 2%. SK-OV-3 gave a lower value of
      0.3%. These TE50 correlate with concentrations of cytosolic NR activity, which is
      distinguished from endogenous DT diaphorase activity by kinetic differences. A
      novel method is described which enables both DNA crosslinks and drug-induced
      single-strand breaks to be simultaneously quantified in a sedimentation assay.
      Using this technique, bystander DNA damage was demonstrated in V79 cells, of
      approximately 50% of that in activator cells.

PMID- 9536272
TI  - In vitro and in vivo antitumor effects of retrovirus-mediated herpes simplex
      thymidine kinase gene-transfer in human medulloblastoma.
AB  - Herpes simplex virus thymidine kinase gene (HSVtk) transfer together with
      treatment with the prodrug ganciclovir (GCV) represents the most commonly used
      suicide gene approach for the gene therapy of human central nervous system
      malignancies. Despite encouraging results reported in clinical trials conducted
      in adults, very little is known about the feasibility of this approach for the
      treatment of CNS tumors of childhood. We studied the effects of the HSVtk/GCV
      system on human medulloblastoma cells in vitro and in vivo. The transfer of tk
      gene to medulloblastoma cells was capable of mediating cell suicide in vitro and
      in vivo upon treatment with GCV, but the overall effect in vivo appeared to be
      suboptimal. The relatively low sensitivity of the medulloblastoma cells to viral
      infection and a limited bystander effect, coupled with a low expression of
      connexin-43 protein, might partially explain these results. Whether this is a
      peculiarity of the cell line studied or a general characteristic of
      medulloblastoma remains to be determined. These findings should be taken into
      account for the future planning of gene therapy trials for human medulloblastoma.

PMID- 9536273
TI  - Treatment of intracranial gliomas in immunocompetent mice using herpes simplex
      viruses that express murine interleukins.
AB  - This report describes a test of the hypothesis that the oncolytic effect of
      genetically engineered, replication competent herpes simplex viruses (HSV)
      depends both on cell destruction by the virus and an immune response to the tumor
      cells induced in an immunocompetent animal system. The oncolytic vector was a HSV
      recombinant virus in which both copies of the gamma 1 34.5 gene were replaced
      with the murine genes encoding the cytokine interleukin-4 (IL-4) or interleukin
      10 (IL-10). The hypothesis predicted that if an immune response plays a role in
      survival following intratumoral treatment of tumor-bearing animals with HSV,
      expression of IL-4 should prolong survival whereas expression of IL-10 should
      reduce it. The results are that (1) these cytokines can be expressed by HSV in
      productively infected cells both in vitro and in vivo; (2) HSV-expressing IL-4 or
      IL-10 genes were able to infect and destroy glioma cells in vitro; (3)
      intracerebral inoculation of HSV expressing either IL-4 or IL-10 into syngeneic
      murine glioma GL-261 cells implanted in the brains of immunocompetent C57BL/6
      mice produced dramatically opposite physiologic responses. The IL-4 HSV
      significantly prolonged survival of tumor bearers, whereas tumor-bearing mice
      that received the IL-10 HSV had a median survival that was identical to that of
      saline treated controls; (4) immunohistochemical analyses of mouse brains at 3
      and 7 days after virus inoculation showed marked accumulation of inflammatory
      cells composed primarily of macrophages/microglia, with various proportions of
      CD8+ and CD4+ T cells, but few B lymphocytes. We conclude that the cytokines
      expressed from genes encoded in the viral genome influence HSV therapy of tumors
      and this is probably due to the host immune response. Thus, cytokine expression
      may be an important adjunct to tumor therapy utilizing genetically engineered
      HSV.

PMID- 9536274
TI  - ICAM-1 induction in respiratory cells exposed to a replication-deficient
      recombinant adenovirus in vitro and in vivo.
AB  - Administration of replication-deficient recombinant adenoviruses (Ad) designed as
      vectors for gene transfer to the airway tract of rats and monkeys has been
      associated with a dose-dependent inflammatory process a few days after viral
      exposure. Among the cellular mechanisms possibly involved, we investigated the
      expression of intercellular adhesion molecule-1 (ICAM-1), which is known to be
      induced by parainfluenza, adenovirus type 5 and respiratory syncytial viruses in
      vitro. To test this hypothesis, an Ad type 5-derived replication-deficient
      recombinant vector carrying the expression cassette for the cystic fibrosis gene
      (Ad.CFTR) was either incubated with A549 cells (a human-derived lung epithelial
      cell line) or instilled by bronchoscopic procedures into the airways of Rhesus
      monkeys. Ad.CFTR induced expression of ICAM-1 in A549 cells and up-regulated with
      time the basal levels of ICAM-1 mRNA in lung portions of Rhesus monkeys. These
      observations indicate that E1-E3-deleted replication-deficient adenoviral vectors
      are capable of inducing adhesion molecules known to play a role in inflammation.

PMID- 9536275
TI  - Inclusion of cholesterol in DOTAP transfection complexes increases the delivery
      of DNA to cells in vitro in the presence of serum.
AB  - The contrast between the relative efficiency of transfection by cationic lipid
      reagents in vitro and that in vivo is well recognised. One suggested reason for
      this is the presence of competing polyanionic surfaces in blood and other
      biological fluids, and even in vitro transfections have to be performed in low
      serum medium. In this study we have shown that by preparing cationic lipid
      reagents based on DOTAP with cholesterol as a second constituent of the bilayer
      we can achieve significant levels of in vitro transfection in serum
      concentrations of up to 80% (DOTAP alone did not transfect at all in these
      conditions). In an effort to explain the behaviour of DOTAP/cholesterol mixes
      under these conditions, we examined the effect of serum on the transfection
      complex. We could detect protein bound to each type of cationic lipid complex,
      but there was no difference in the amount nor in the type of protein bound. DNA
      within either type of complex which were incubated with increasing amounts of
      serum remained resistant to digestion with DNase I, and there was no reduction in
      the condensation of the DNA as measured by ethidium bromide fluorescence.
      Finally, we measured the attachment and uptake into cells by the different
      complexes in the presence of serum and showed that more DOTAP-cholesterol than
      DOTAP complexes attach to and are taken up by cells in the presence of serum. We
      suggest that improved cell binding and uptake may be the main mechanism by which
      cholesterol acts to maintain transfection in the presence of serum.

PMID- 9536277
TI  - Cadherin and catenin biology represent a global mechanism for epithelial cancer
      progression.
AB  - The cell undergoes a diverse range of stimulations including growth factor
      activation and signal transduction from adhesion receptors, such as cadherins. In
      the absence of a mitogenic signal from outside the cell, beta catenin is
      sequestered in complexes with the product of the adenomatous polyposis coli (APC)
      gene and a serine threonine glycogen kinase (GSK 3 beta) enabling degradation of
      free beta catenin. Residual catenins hold cells together by binding to cadherins
      both at adherens junctions and the actin cytoskeleton. When a mitotic signal is
      delivered by the wnt pathway, GSK 3 beta is antagonised so that beta catenin can
      no longer be degraded. Cytosolic concentrations rise and binding to other newly
      synthesised proteins occurs, especially transcription factors that are
      transported to the nucleus, such as lymphocyte enhancing factor and T cell
      factor. This article discusses the signalling between mitogenic and adhesion
      pathways and suggests that it is a global mechanism for development,
      differentiation, and disease. These changes in catenin and APC biology may not be
      sufficient alone to transform cells fully but they appear to be a necessary final
      common pathway for several cancers of the mucous secreting crypts (including
      Barrett's oesophageal lesions and colorectal cancer) or stratified secreting
      epithelium (melanoma) before invasion.

PMID- 9536276
TI  - Genetic prognostic markers in colorectal cancer.
AB  - The contribution of molecular genetics to colorectal cancer has been restricted
      largely to relatively rare inherited tumours and to the detection of germline
      mutations predisposing to these cancers. However, much is now also known about
      somatic events leading to colorectal cancer. A number of studies has been
      undertaken examining possible relations between genetic features and prognostic
      indices. While many of these studies are small and inconclusive, it is clear that
      a number of different pathways exist for the development of this cancer and some
      molecular characteristics correlate with clinicopathological features. With the
      advent of methods for the rapid genotyping of large numbers of colorectal
      cancers, it should be possible to evaluate fully the clinical usefulness of
      colorectal cancer genotypes through multivariate analyses.

PMID- 9536278
TI  - Modification of cystatin C activity by bacterial proteinases and neutrophil
      elastase in periodontitis.
AB  - AIM: To study the interaction between the human cysteine proteinase inhibitor,
      cystatin C, and proteinases of periodontitis associated bacteria. METHODS:
      Gingival crevicular fluid samples were collected from discrete periodontitis
      sites and their cystatin C content was estimated by enzyme linked immunosorbent
      assay (ELISA). The interaction between cystatin C and proteolytic enzymes from
      cultured strains of the gingival bacteria Porphyromonas gingivalis, Prevotella
      intermedia, and Actinobacillus actinomycetemcomitans was studied by measuring
      inhibition of enzyme activity against peptidyl substrates, by detection of break
      down patterns of solid phase coupled and soluble cystatin C, and by N-terminal
      sequence analysis of cystatin C products resulting from the interactions.
      RESULTS: Gingival crevicular fluid contained cystatin C at a concentration of
      approximately 15 nM. Cystatin C did not inhibit the principal thiol stimulated
      proteinase activity of P gingivalis. Instead, strains of P gingivalis and P
      intermedia, but not A actinomycetemcomitans, released cystatin C modifying
      proteinases. Extracts of five P gingivalis and five P intermedia strains all
      hydrolysed bonds in the N-terminal region of cystatin C at physiological pH
      values. The modified cystatin C resulting from incubation with one P gingivalis
      strain was isolated and found to lack the eight most N-terminal residues. The
      affinity of the modified inhibitor for cathepsin B was 20-fold lower (Ki 5 nM)
      than that of full length cystatin C. A 50 kDa thiol stimulated proteinase,
      gingipain R, was isolated from P gingivalis and shown to be responsible for the
      Arg8-bond hydrolysis in cystatin C. The cathepsin B inhibitory activity of
      cystatin C incubated with gingival crevicular fluid was rapidly abolished after
      Val10-bond cleavage by elastase from exudate neutrophils, but cleavage at the
      gingipain specific Arg8-bond was also demonstrated. CONCLUSIONS: The
      physiological control of cathepsin B activity is impeded in periodontitis, owing
      to the release of proteinases from infecting P gingivalis and neutrophils, with a
      contribution to the tissue destruction seen in periodontitis as a probable
      consequence.

PMID- 9536279
TI  - Immunohistochemical pattern of insulin-like growth factor (IGF) I, IGF II and IGF
      binding proteins 1 to 6 in carcinoma in situ of the testis.
AB  - AIM: To study the immunohistochemical localisation of insulin-like growth factor
      (IGF) I, IGF II, and IGF binding proteins 1-6 in intratubular germ cell neoplasia
      in the vicinity of solid germ cell tumours of the testis. METHODS: Testes were
      obtained from 13 patients (20-35 years old) who had undergone orchidectomy for
      treatment of a solid germ cell tumour. Tumour cells were verified histologically
      by their distinctive morphology and by visualisation of placental alkaline
      phosphatase immunoreactivity. RESULTS: The majority of carcinoma in situ (CIS)
      cells were immunopositive for IGF I, whereas no CIS cells stained for IGF II. Of
      all the IGF binding proteins investigated, CIS cells showed intense
      immunoreactivity for IGF binding protein 5 and lower expression of all other IGF
      binding proteins. CONCLUSIONS: These results suggest that the action of IGF
      binding protein 5 in CIS cells may modulate the activity of IGF I. This may be
      related to a proliferative advantage that could facilitate tumour development.

PMID- 9536280
TI  - Microvessel density, p53 overexpression, and apoptosis in invasive breast
      carcinoma.
AB  - AIM: To investigate the possibility of a correlation among microvessel density,
      p53 overexpression, and apoptosis in invasive breast carcinoma. METHODS:
      Microvessel density was analysed in 105 cases of invasive breast carcinoma by
      immunohistology using antifactor VIII related antibody. The results were
      correlated with the immunohistochemical expression of p53 and the apoptotic
      index, detected using the in situ end labelling of fragmented DNA method (TUNEL).
      Assessment was made with a CAS 200 image analyser. All these studies were
      performed on formalin fixed, paraffin wax embedded tissue sections of tumour
      samples. RESULTS: The mean (SD) microvessel count was 47.2 (51.1), with a range
      from 7 to 250. Thirty five (33%) carcinomas showed overexpression of p53 protein.
      The apoptotic index of tumours ranged from 0.0 to 28.0, with a mean (SD) of 1.7
      (3.2). The results showed that there was a significant inverse correlation
      between microvessel density and p53 expression (p = 0.04; odds ratio, 0.37). In
      contrast, no correlation was identified between the microvessel density and
      apoptotic index. CONCLUSIONS: These results suggest that in invasive breast
      carcinoma the p53 overexpression phenotype downregulates tumour neoangiogenesis,
      as does the wild-type of p53 protein. In addition, they suggest that apoptosis
      and neoangiogenesis in these tumours are independent processes.

PMID- 9536281
TI  - Chromosomal mapping and expression of the human cyr61 gene in tumour cells from
      the nervous system.
AB  - AIMS: To characterise the human cyr61 gene (cyr61H) and determine its chromosomal
      locality. To compare expression of cyr61H in human tumour cell lines with that of
      two other structurally related genes, novH (nephroblastoma overexpressed gene)
      and CTGF (connective tissue growth factor), that are likely to play a role in the
      control of cell proliferation and differentiation. METHODS: To isolate the human
      cyr61 gene, placental genomic and HeLa cDNA libraries were screened with murine
      cyr61 cDNA. The nucleotide sequence of the complete cyr61H cDNA was established.
      Both Southern blotting of a panel of somatic cell hybrids and in situ
      hybridisation on chromosomes were performed to map the cyr61H gene. Expression of
      cyr61H, novH, CTGF, and novH was analysed by northern blotting in both human
      neuroblastomas and glioblastoma cell lines. RESULTS: Genomic and cDNA clones
      encompassing the cyr61H gene were isolated and characterised. Comparison of mouse
      and human cyr61 sequences indicated that their genomic organisation is highly
      conserved. Alignment of coding sequences highlighted the conservation of cyr61
      regions that might be critical for its biological function. The data showed that
      the cyr61H gene is assigned to chromosome 1p22.3 and that different levels of
      cyr61H, CTGF, and novH mRNA have been detected in several human tumour cell lines
      derived from the nervous system. CONCLUSIONS: The human cyr61 gene belongs to an
      emerging family of genes including CTGF/fisp12 and nov. The murine cyr61 encodes
      an extracellular cysteine rich protein that exhibits chemotactic activity,
      promotes attachment and spreading of cells, and potentiates the mitogenic effect
      of growth factors. Assignment of the cyr61H gene to chromosome 1p22.3 will allow
      studies to determine whether human pathologies derived from the nervous system or
      from other tissues are associated with chromosomal abnormalities involving this
      region. Although the coding regions of cyr61H, CTGF, and novH are highly
      homologous, a growing body of evidence suggests that expression of these genes is
      regulated differentially, and that a balance between expression of these genes
      might represent a key element in determining the stage of differentiation and/or
      the malignant potential of tumour cells.

PMID- 9536282
TI  - Double immunostaining for p53 and molecular chaperone hsp72/73 in gastric
      carcinoma.
AB  - AIMS: To examine the relation between the expression of p53 protein and the
      chaperone heat shock protein (hsp)72/73 in a population at high risk for gastric
      carcinoma, using single and double immunohistochemistry, and to compare the
      expression of these two proteins with clinicopathological features. METHODS:
      Monoclonal antibodies were used to investigate the expression of p53 protein and
      hsp72/73 in 46 human gastric carcinomas. A double immunohistochemical technique
      was used in cases that showed p53/hsp72/73 coexpression. RESULTS: p53
      immunoreactivity was present in 11 tumours (24%), and hsp72/73 immunostaining was
      observed in 22 cases (48%). p53 expression was observed as nuclear staining in
      tumoral cells. hsp72/73 expression was demonstrated mainly as cytoplasmic
      staining, but six tumours also showed focal weak nuclear staining. Seven cases
      showed p53 and hsp72/73 coexpression with immunoreactivity for both proteins in
      the same neoplastic cells, three of them with focal areas of nuclear
      coexpression. p53 expression was seen more frequently in cases that showed a high
      intensity (+ + +) of hsp72/73 staining. No significant association was observed
      between the expression of the two proteins and clinicopathological features.
      CONCLUSIONS: More than half of our cases may have some impairment in p53 protein
      growth suppressive function, as a result of p53 gene alterations or complex
      formation. The positive correlation between p53 expression and intensity of
      hsp72/73 supports the postulate of a p53 regulating function for the chaperone
      hsp72/73. A high intensity of hsp72/73 immunohistochemical staining could be used
      as an indirect marker of p53 gene abnormalities.

PMID- 9536283
TI  - Amplification of fluorescent in situ hybridisation signals in formalin fixed
      paraffin wax embedded sections of colon tumour using biotinylated tyramide.
AB  - Fluorescent in situ hybridisation (FISH) is a powerful tool for the evaluation of
      chromosomal alterations in formalin fixed paraffin wax embedded sections of
      colorectal cancer. However, initial experiments using a two-step detection system
      for digoxigenin labelled chromosome specific centromeric probes resulted in a
      complete lack of hybridisation signal from a number of colorectal tumour
      sections. This was due to high levels of background autofluorescence observed in
      this tissue, which masked any relatively weak hybridisations present. To overcome
      this problem, a biotinylated tyramide mediated amplification system was
      incorporated into the FISH detection protocol. This involves the use of
      horseradish peroxidase to activate the biotinylated tyramide, resulting in the
      deposition of a large number of biotin molecules at the site of bound peroxidase,
      which corresponds directly to the location of hybridised probe. Final detection
      was by means of a streptavidin-FITC conjugate. Using this technique, a panel of
      11 colorectal tumour samples studied to date have shown strong, specific
      hybridisation signals to the nucleus of tumour cells. Amplification of FISH
      signals by biotinylated tyramide has the potential to improve weak hybridisation
      signals in cells from numerous sources, using a variety of probe types, including
      single copy gene probes as well as centromere specific probes.

PMID- 9536284
TI  - Heterogeneity of clonal lymphocytes with regard to bcl-2 protein concentration
      and cell size.
AB  - The existence of subpopulations of clonal lymphocytes in patients with low grade
      lymphoproliferative disorders, with regard to both cell size and bcl-2 protein
      concentration is reported. Flow cytometric analysis showed that the lymphocytes
      with higher levels of bcl-2 corresponded to a subset of larger lymphocytes.
      Statistical analysis suggested that the increased concentration of bcl-2 was not
      accounted for by the increase in cell size and it is possible that these cells
      form a functionally distinct component of the clonal proliferation. One patient,
      analysed in greater detail during treatment with a purine analogue, showed the
      subpopulations to exhibit a differential sensitivity to chemotherapy.

PMID- 9536285
TI  - p53 mutations in multiple myeloma.

PMID- 9536286
TI  - Differences in patellofemoral joint cartilage material properties and their
      significance to the etiology of cartilage surface fibrillation.
AB  - OBJECTIVE: To determine if differences in biomechanical properties and
      biochemical composition exist between human patellar articular cartilage and the
      opposing femoral articular cartilage. DESIGN: The biomechanical properties and
      biochemical composition of the articular cartilage of 17 knees from 13 donors
      were determined for four sites on the patella and three sites on the femur
      representing regions of contact at 30 degrees and 90 degrees of flexion. The
      material properties were determined by biphasic indentation testing, yielding the
      compressive aggregate modulus, HA, permeability, k, and Poisson's ratio, vs. The
      thickness of the cartilage at the indentation site, h, was also measured using a
      needle probe. Full-thickness samples of cartilage adjacent to each indentation
      site were used for wet weight, sulfated glycosaminoglycan content and
      hydroxyproline content determinations. RESULTS: The patellar cartilage was found
      to have a lower compressive aggregate modulus by 30% (P < 0.001), higher
      permeability to fluid flow by 66% (P < 0.001) and greater thickness by 23% (P =
      0.017) than that of the opposing femoral cartilage. The Poisson's ratios for both
      surfaces were found to be nearly zero. The water content of the patella was
      higher by 5% (P = 0.031) and the proteoglycan content lower by 19% (P = 0.030)
      than that of the femur. However, no differences were found between the collagen
      contents of the cartilages. CONCLUSIONS: Significant differences were found
      between the intrinsic material properties of the patellar cartilage and those of
      the femoral-trochlear cartilage. This variability of cartilage material
      properties with the patellofemoral joint may help explain why patellar cartilage
      has been frequently observed clinically to exhibit earlier and more severe
      fibrillation changes than the opposing femoral cartilage.

PMID- 9536287
TI  - Ultrastructural immunolocalization of bone sialoprotein in guinea-pig
      osteoarthritis.
AB  - In diarthrodial joints, bone and cartilage are structurally and functionally
      inseparable as shown in osteoarthritis (OA), where subchondral bone changes are
      integral in the disease process. By ultrastructural immunohistochemistry using
      polyclonal antibodies against guinea-pig bone sialoprotein (BSP), we investigated
      the distribution of this matrix protein at the osteocartilaginous interface in
      Hartley guinea-pig knees at different stages of primary osteoarthritis. Between 6
      and 12 months they developed moderate osteoarthritic changes predominantly in the
      medial condyle, progressing to severe OA at 30 months. In all age groups BSP
      labeling was concentrated to the osteocartilaginous interface at a 1 micron
      narrow zone at the interface. In the medial osteoarthritic condyle, BSP was
      increased as compared with the lateral nonosteoarthritic condyle, but only at 30
      months, when cartilage fibrillation correlated to BSP. Our observations suggest
      that altered BSP abundance may be a potential bone marker for late stage OA,
      while early events in bone cannot be monitored. BSP is expressed early in
      osteogenesis and may have a role in biological mineralization and growth. Since a
      sharp zone of intense BSP labeling remains at a remarkably constant level
      throughout life in guinea-pigs, BSP may have an important structural and/or
      regulating role at the interface. The protein may act as an anchor of calcified
      articular cartilage to subchondral bone or by regulating mineralization at the
      osteocartilaginous interface.

PMID- 9536288
TI  - Differentiation-dependent and stimulus-specific expression of ILA, the human 4
      1BB-homologue, in cells of mesenchymal origin.
AB  - OBJECTIVE: Examine the expression of ILA, a member of the human NGF/TNF receptor
      family and the homologue of the murine 4-1BB, in mesenchymal cells. METHODS: ILA
      mRNA was analyzed by quantitative polymerase chain reaction and Northern blotting
      in human articular chondrocytes and fibroblasts. ILA protein expression was
      examined by flow cytometry. RESULTS: The proinflammatory stimuli interleukin-1
      beta (IL-1 beta), tumour necrosis factor (TNF) alpha, leukemia inhibitory factor
      (LIF), interferon (IFN) gamma and lipopolysaccharide (LPS) induced ILA mRNA in
      primary human articular chondrocytes. TGF beta and dexamethasone inhibited IL-1
      induced ILA expression. Chondrocytes expressed the 4.8, 4.0 and 1.9 kb isoforms
      of ILA mRNA which had previously been observed in lymphocytes and additional
      isoforms at 3.2, 1.5 and 1.2 kb. Cycloheximide alone induced ILA mRNA in primary
      chondrocytes while the combination of IL-1 and cycloheximide resulted in ILA
      superinduction. In contrast to primary chondrocytes, activated human synovial or
      skin fibroblasts did not express ILA mRNA. Furthermore, ILA was no longer
      inducible by IL-1 in subcultured, dedifferentiated chondrocytes. However,
      repression of ILA in fibroblasts and dedifferentiated chondrocytes was overcome
      by cycloheximide and IL-1 further increased ILA mRNA levels in the presence of
      cycloheximide. Flow cytometric analysis of ILA protein expression with monoclonal
      antibodies revealed increased cell-surface expression on IL-1 or TNF alpha, but
      not on TGF beta stimulated chondrocytes. CONCLUSION: ILA is not only expressed in
      the immune system but also in mesenchymal cells. ILA expression is induced by
      specific stimuli and modulated by the differentiation status of the cells. ILA
      can serve as a model and marker to analyze differentiation-dependent gene
      expression in mesenchymal cells.

PMID- 9536289
TI  - Aggrecanase and metalloproteinase-specific aggrecan neo-epitopes are induced in
      the articular cartilage of mice with collagen II-induced arthritis.
AB  - OBJECTIVE: To analyze the roles of two classes of proteinases, 'aggrecanase', and
      matrix metalloproteinases (MMPs), in chondrodestruction during murine collagen
      induced arthritis (CIA). METHODS: Generation of the 'aggrecanase' neo-epitope
      (NITEGE373), and the MMP neo-epitope (VDIPEN341) within aggrecan was studied by
      immunoperoxidase microscopy using specific anti-peptide antibodies in normal and
      stromelysin-1 (SLN-1) deficient knockout mice with CIA. RESULTS: High levels of
      NITEGE373 and VDIPEN341 neo-epitopes were observed in foci within CIA paw
      articular cartilage exhibiting depletion of glycosaminoglycans, in advance of
      significant cartilage erosion. The highest concentrations of NITEGE373 and
      VDIPEN341 labeling were observed and often co-distributed in the chondrocyte
      pericellular matrix, suggesting that stimulated chondrocytes can synthesize
      and/or activate both enzymes. Other regions of the cartilage frequently exhibited
      either NITEGE373 or VDIPEN341 labeling, but not both neo-epitopes simultaneously,
      suggesting that 'aggrecanase' and MMP cleavages of aggrecan may be generated
      independently. No detectable differences were observed in expression or
      distribution of either neo-epitope in SLN-1 knockout versus wild-type mice. In
      addition, in vitro digestion of joint sections with SLN-1 did not alter the
      expression of cartilage NITEGE373, while markedly increasing VDIPEN341 labeling.
      Peripheral nerves and brains of naive mice also exhibited intense anti-NITEGE373
      labeling. CONCLUSIONS: These data indicate that NITEGE373 and VDIPEN341 aggrecan
      neo-epitopes are sensitive and specific markers of early joint pathology, and are
      consistent with the hypothesis that SLN-1 does not have 'aggrecanase' activity,
      and that 'aggrecanase' is distinct from the MMPs which cleave aggrecan at the MMP
      site.

PMID- 9536290
TI  - Comparison of synovial fluid cartilage marker concentrations and chondral damage
      assessed arthroscopically in acute knee injury.
AB  - OBJECTIVE: To examine the correlation between synovial fluid cartilage markers
      and degree of cartilage damage determined by arthroscopic evaluation in subjects
      with acute knee injury. DESIGN: Chondral damage was quantified using a validated
      arthroscopic scoring system in 20 subjects with effusive acute knee injuries of
      less then 4 months duration and no history or radiographic evidence of joint
      pathology. Levels of synovial fluid 3B3(-) neoepitope, 3B3(+) chondroitinase
      generated epitope of proteoglycan, keratan sulfate (KS) and hyaluronic acid (HA)
      were measured by competitive enzyme-linked immunosorbent assays using monoclonal
      antibodies 3B3 and 5D4. Total sulfated glycosaminoglycan (GAG) was measured by
      1,9-dimethylmethylene blue colorimetric dye-binding assay. RESULTS: We found a
      dramatic decrease in levels of 3B3(-) (rs = -0.62, P = 0.004), and GAG (rs = 
      0.49, P = 0.03) with increasing chondral damage score; but no correlation of
      damage score with 3B3(+), KS or HA levels. CONCLUSION: These data reveal a change
      in cartilage metabolism within the first 4 months of symptomatic knee injury
      evinced by a significant inverse correlation of 3B3(-) and GAG levels to chondral
      lesion severity. These results suggest that serial measurement of these synovial
      fluid markers in the setting of acute knee injury could predict chondral lesion
      severity and aid in the decision to intervene surgically.

PMID- 9536291
TI  - Chondrocyte tumor necrosis factor receptors and focal loss of cartilage in
      osteoarthritis.
AB  - OBJECTIVE: Osteoarthritis (OA) is characterized by focal loss of cartilage. Here
      we show for the first time that tumor necrosis factor (TNF) alpha can act on
      cartilage but only at specific sites where chondrocyte TNF alpha-receptor (R)
      expression is high. DESIGN: Cartilage explants from specified sites in the knee
      joints of both OA patients and non-arthritic (NA) subjects were cultured with and
      without TNF alpha for 14 days and cumulative glycosaminoglycan (GAG) release into
      the supernatant measured. p55 and p75 TNF-R expression was measured by flow
      cytometry on chondrocytes isolated from the same sites. RESULTS: Cartilage
      explants from different sites in knee joints from both OA patients and NA
      subjects varied in their susceptibility to TNF alpha. Overall, the proportion of
      samples that responded to TNF alpha was higher in cartilage taken from OA joints
      than cartilage from NA subjects. Variations in p55 and p75 TNF-R expression were
      found between chondrocytes from different sites. p55, but not p75 TNF-R,
      expression on chondrocytes was closely related to the susceptibility of explants
      from the same site to TNF alpha-induced GAG loss. CONCLUSION: It is considered
      that focal loss of cartilage will occur at sites where chondrocyte p55 TNF-R
      expression is high, if sufficient TNF alpha is present, and that these results
      identify a mechanism by which cytokine-mediated focal loss of cartilage may
      occur.

PMID- 9536293
TI  - Cartilage chondrolysis by fibronectin fragments causes cleavage of aggrecan at
      the same site as found in osteoarthritic cartilage.

PMID- 9536292
TI  - Effects of diacerhein in an accelerated canine model of osteoarthritis.
AB  - OBJECT: To determine whether diacerhein has a disease-modifying effect in an
      accelerated canine model of osteoarthritis. DESIGN: Fourteen adult mongrel dogs
      underwent unilateral L4-S1 dorsal root ganglionectomy (DRG), followed 3 weeks
      later by ipsilateral anterior cruciate ligament transection. Seven dogs received
      diacerhein (15-20 mg/kg) daily throughout the interval between DRG and sacrifice,
      eight weeks after ligament transection. The other seven dogs served as OA
      controls. RESULTS: The mean volume of synovial fluid obtained from the OA knee of
      the diacerhein-treated dogs was approximately 40% less than that from the OA knee
      of the controls. In addition, diacerhein appeared to reduce the severity of
      fibrillation (femoral condyle) and full-thickness ulceration (trochlear ridge) of
      the articular cartilage and the level of collagenase activity in extracts of the
      OA cartilage, and to increase net PG synthesis in the OA cartilage, although none
      of the above changes were statistically significant. CONCLUSION: The differences
      between the diacerhein group and untreated OA controls, even though not
      statistically significant, suggest that diacerhein was active in this rapidly
      progressive model of OA. Because changes associated with initiation of OA may be
      different than those associated with progression, whether diacerhein has a
      disease-modifying effect should be examined in a less rapidly progressive model.

PMID- 9536294
TI  - Osteoporosis update 1997.

PMID- 9536295
TI  - Osteoporosis: past, present and future.
AB  - Osteoporosis is an old and continuing problem which has been a challenge to
      medical research and care throughout the history of mankind. After the break
      through with estrogen, many new agents as well as nutritional and physical
      interventions were found to be effective in preventing and controlling
      osteoporosis. Calcium represents one of the keys to all these methods, especially
      with the appearance of new highly biologically available forms influencing cell
      calcium metabolism. It appears to be important to focus our attention not only on
      the physical properties and strength of bone but also on its calcium storage
      function. By controlling osteoporosis and restoring the proper calcium storage
      function of the bone, many diseases of old age which are due to or exacerbated by
      calcium deficiency and disturbed calcium distribution in the body, such as
      hypertension, arteriosclerosis and senile dementia, may also be successfully
      controlled.

PMID- 9536296
TI  - Genetic and environmental components of the population variance in bone density.
AB  - Understanding of the genetic and environmental factors contributing to the
      differences in fracture rates between young and old, between women and men, and
      between races is limited. The reasons for this may partly relate to the lack of a
      detailed understanding of the structural basis of bone fragility. This
      information, although difficult to obtain because of the invasiveness of bone
      biopsy, will be required if advances are to occur. aBMD cannot be relied upon as
      an endpoint in the study of the pathophysiology of osteoporosis. Advances will
      require the description of the age-, gender and race-specific means and variances
      in trabecular number, thickness, spacing and orientation, cortical thickness, and
      bone size and shape in women and men of different racial groups. Subsequent
      comparison of the structures in young versus old, female versus male, and in
      racial groups may reveal the structural differences from which inferences may be
      made concerning the differences in fracture rates between these groups. By
      defining the structural basis for bone fragility, the genetic and modifiable
      environmental determinants of these structures may then be identified, providing
      hypotheses to be tested in randomized trials aimed at reducing the incidence of
      fractures in these groups.

PMID- 9536297
TI  - The calcium controversy.

PMID- 9536298
TI  - 1,25-Dihydroxyvitamin D3 in the pathogenesis and treatment of osteoporosis.

PMID- 9536299
TI  - Significance of albumin in the pathogenesis of osteoporosis: bone changes in
      genetically analbuminemic rats and rats fed a low albumin diet.

PMID- 9536300
TI  - Protein intake, IGF-1 and osteoporosis.

PMID- 9536301
TI  - Pathogenesis of bone loss due to estrogen deficiency.

PMID- 9536302
TI  - Cytokines in the pathogenesis of osteoporosis.

PMID- 9536304
TI  - Immobilization as the pathogenesis of osteoporosis: experimental and clinical
      studies.

PMID- 9536303
TI  - Integrins and osteoclast polarization.

PMID- 9536305
TI  - Changes in bone and calcium metabolism with space flight.

PMID- 9536306
TI  - Epidemiology of osteoporosis in the United States of America.

PMID- 9536307
TI  - Epidemiology of osteoporosis in South America.

PMID- 9536308
TI  - Epidemiology of Osteoporotic Fractures in Europe: towards biologic mechanisms.
      The European Prospective Osteoporosis Study Group.

PMID- 9536309
TI  - Epidemiology of primary osteoporosis in China.

PMID- 9536310
TI  - Epidemiology of osteoporosis in Korea.

PMID- 9536311
TI  - Epidemiology of osteoporosis in urbanized Asian populations.

PMID- 9536312
TI  - Epidemiology of osteoporosis in Taiwan.

PMID- 9536313
TI  - Epidemiology of osteoporosis in Japan.

PMID- 9536314
TI  - Radiographic absorptiometry for measuring bone mass.

PMID- 9536315
TI  - Diagnosis of osteoporosis.

PMID- 9536316
TI  - Utility of dual X-ray absorptiometry and single X-ray absorptiometry as
      diagnostic tools for involutional osteoporosis.

PMID- 9536317
TI  - Peripheral QCT for the diagnosis of osteoporosis.

PMID- 9536318
TI  - Quantitative ultrasound for the assessment of bone status.

PMID- 9536319
TI  - High-resolution magnetic resonance imaging of trabecular bone structure.

PMID- 9536320
TI  - Treatment of osteoporosis with vitamin D.

PMID- 9536321
TI  - The strategy for the treatment of osteoporosis.

PMID- 9536322
TI  - Oestrogen effects on calcium membrane transport: a new view of the inter
      relationship between oestrogen deficiency and age-related osteoporosis.

PMID- 9536323
TI  - Vitamin D for the treatment of osteoporosis.

PMID- 9536324
TI  - Calcitonin in the treatment of osteoporosis.

PMID- 9536325
TI  - Parathyroid hormone in the treatment of involutional osteoporosis: back to the
      future.

PMID- 9536326
TI  - The history of parathyroid hormone and its receptor: structure-based design of
      parathyroid hormone analogues.

PMID- 9536327
TI  - Ipriflavone for the treatment of osteoporosis.

PMID- 9536328
TI  - Vitamin D and analogues in renal bone disease and implications for osteoporosis.

PMID- 9536329
TI  - Pathogenesis and histology of renal osteodystrophy.

PMID- 9536330
TI  - Osteoporosis and atherosclerosis in chronic renal failure.

PMID- 9536331
TI  - Changes in bone mineral density at various sites in patients on hemodialysis due
      to chronic glomerulonephritis.

PMID- 9536332
TI  - Clinical and pathogenic factors in dialysis-related amyloidosis: current research
      findings.

PMID- 9536333
TI  - Vitamin D and its analogs in chronic renal failure.

PMID- 9536334
TI  - Importance of sustained high glucose condition in the development of diabetic
      osteopenia: possible involvement of the polyol pathway.

PMID- 9536335
TI  - Steroid-induced osteoporosis.

PMID- 9536336
TI  - Osteoporosis in rheumatoid arthritis.
AB  - Periarticular osteopenia of appendicular bones occurs early in the course of RA.
      Loss of the balance between bone resorption and formation contributes to the
      development of periarticular osteopenia and might be mediated through increased
      production of cytokines and prostaglandins by the synovium and bone marrow.
      Generalized osteopenia is also common and leads to an increased risk of fracture.
      Although the pathogenesis of this osteopenia is considered to be multifactorial,
      disease activity, immobility, corticosteroids and menopausal status are the
      important determinants.

PMID- 9536337
TI  - Mechanisms of exercise limitation in chronic heart failure and the role of
      rehabilitation.

PMID- 9536338
TI  - Gastric carcinoma: clinical, pathogenic, and molecular aspects.

PMID- 9536339
TI  - Plasmodium vivax: a cause of malnutrition in young children.
AB  - We studied the aetiology of malnutrition in a cohort of 1511 children < 10 years
      old in Espiritu Santo, Vanuatu. Malnutrition was categorized using standard
      anthropometric criteria as: underweight [weight-for-age (WA) Z score < -2],
      wasting [weight-for-height (WH) Z < -2], or stunting [height-for-age (HA) Z < 
      2]. On multiple logistic regression analysis, the only factors significantly
      associated with wasting were age < 5 years [OR (95% CI) 1.8 (1.2-2.9), p = 0.01]
      and having suffered one or more episodes of clinical P. vivax malaria in the 6
      months preceding nutritional assessment [OR 2.4 (1.3-4.4), p = 0.006]. The
      incidence of P. vivax infection was significantly higher during the 6 months
      preceding assessment in underweight vs. non-underweight children [incidence rate
      ratio (IRR) 2.6 (1.5-4.4), p < or = 0.0001). These groups had similar incidences
      of clinical P. falciparum infection during the same period [IRR 1.1 (0.57-2.1) p
      = 0.8] and of either species during the 6 months following assessment [IRR P.
      vivax 1.3 (0.9-2.0) p = 0.2; IRR P. falciparum 1.3 (0.9-1.9) p = 0.2]. In these
      children, P. vivax malaria was a major predictor of acute malnutrition; P.
      falciparum was not. Wasting neither predisposed to nor protected against malaria
      of either species. Although P. vivax malaria is generally regarded as benign, it
      may produce considerable global mortality through malnutrition.

PMID- 9536340
TI  - Overdiagnosis of TIA and minor stroke: experience at a regional neurovascular
      clinic.
AB  - We compared the referral diagnoses of TIAs and minor strokes made by non
      specialists with those of two consultant neurologists, in 565 consecutive
      cerebrovascular clinic patients, of whom 508 (90%) were referred with a diagnosis
      of any TIA or stroke. In 373 (73%), the neurologists felt the diagnosis of a
      cerebrovascular event to be correct. Agreement with the vascular syndrome (CVA
      vs. TIA) was significantly higher for patients with a referral diagnosis of
      stroke (136/176) (77%) than it was for patients with a referral diagnosis of TIA
      (200/332) (60%) (difference in proportions 17%, 95% CI 9-25). In 37 patients (7%)
      the neurologists confirmed the diagnosis of cerebrovascular disease but not the
      specific TIA/stroke diagnosis. Vascular surgeons were more likely to be correct
      in their referral diagnosis of carotid territory cerebrovascular disease (88%
      correct) than all other sources combined (63% correct) (difference in proportions
      25%, 95% CI 11-39), but there was no significant variation in diagnostic accuracy
      between other individual groups. In 135/508 patients (27%) referred as any TIA or
      stroke, the diagnosis of cerebrovascular disease was undone. Alternative
      diagnoses included migraine (3%), epilepsy (1%), hyperventilation (1%), multiple
      sclerosis (1%) and a case of idiopathic Parkinson's disease, but many symptoms
      (8%) were unclassifiable. A strict comparison of diagnostic accuracy would have
      required assessment of patients not referred for specialist opinion, to estimate
      false-negative as well as false-positive diagnoses. However, in this patient
      group (which reflects current local practice) TIAs and strokes seem
      overdiagnosed.

PMID- 9536341
TI  - Whipple's disease without malabsorption: new atypical features.
AB  - The diagnosis of Whipple's disease in the absence of intestinal involvement is
      difficult and often overlooked. We describe five patients aged 8-71 years with
      normal jejunal biopsies and disparate clinical features, previously unrecognized
      in Whipple's; all were investigated at a single institution over a period of 18
      months. Routine histological examination for periodic acid-Schiff (PAS) positive
      macrophages and polymerase chain reaction (PCR) analysis for Tropheryma whippelii
      was performed on the small intestine in all patients. PCR analysis was also
      performed on various tissues including peripheral blood, lymph node, muscle,
      synovium and spleen in individual patients. Patients 1, 2, 4 and 5 had unusual
      presenting features not previously associated with Whipple's: intractable immune
      thrombocytopenic purpura (ITP), juvenile chronic arthritis, isolated muscle
      weakness and quadriparesis, respectively. Patient 3 presented with pyrexia of
      unknown origin. All patients had histologically normal small-bowel biopsies with
      no evidence of PAS positive macrophages. PCR for T. whippelii was positive in all
      patients in one or more tissues: peripheral blood, intestine, muscle, lymph node
      and synovium. PAS-positive macrophages were found in 4/5 patients in various
      sites: lymph node, muscle, spinal cord. Whipple's disease presents with protean
      clinical features and should be considered in granulomatous disorders of unknown
      aetiology even in the absence of gastrointestinal involvement.

PMID- 9536342
TI  - Presentation and survival of patients with severe renal failure and myeloma.
AB  - We reviewed the clinical features and outcome of 56 patients with myeloma and
      severe renal failure managed in a single institution over a 15-year period. Renal
      failure was recognized within 2 months of the diagnosis of myeloma in 75% of
      patients, and was the initial presentation of myeloma in 50%. Patients were
      staged by the Durie and Salmon classification. Light-chain and IgD myeloma
      accounted for 46% of cases, and Bence-Jones proteinuria was identified in > 90%.
      In 43%, a potential precipitant of renal failure was identified, usually
      hypercalcaemia or a non-steroidal anti-inflammatory agent. A preserved corrected
      calcium at presentation was characteristic (2.40 +/- 0.15 mmol/l, n = 42), even
      after excluding those with hypercalcaemia requiring specific intervention (n =
      14, 2.76 +/- 0.51; p < 0.01): this finding in patients with unexplained acute
      renal failure should alert clinicians to the possibility of myeloma. Forty-seven
      patients (84%) required dialysis. Only seven (15%) ever regained renal function.
      Median survival (all patients) was 8 months. One-third died within 3 months of
      referral and one-third survived > 1 year. Hypoalbuminaemia and reduced platelet
      count at presentation were associated with reduced survival, but hypercalcaemia,
      infection, dialysis, (urgent or long-term), and dialysis modality were not.
      Chemotherapy was associated with increased survival, but progression of myeloma
      and infection were the two most frequent causes of death. Severe renal failure
      was associated with advanced myeloma stage and light-chain/IgD paraproteinaemia.
      Survival was related to severity of myeloma and not requirement for dialysis per
      se.

PMID- 9536343
TI  - Acute renal failure: factors influencing nephrology referral and outcome.
AB  - We investigated the incidence, factors affecting referral and outcome of acute
      renal failure (ARF), in an unselected (predominantly Caucasian) population in the
      Grampian region of Scotland served by a single renal unit. Case-notes were
      examined for all patients with a serum creatinine > or = 300 mumol/l. ARF (311
      patients) was defined as a temporary rise in serum creatinine > or = 300 mumol/l,
      or, if the patient died during the acute illness, clinical features indicating
      acute deterioration of previously normal renal function. Advanced ARF at
      presentation (51 of the 311 with ARF) was defined as a first recorded serum
      creatinine > or = 500 mumol/l. Patients were classified into low-, medium-, and
      high-risk groups according to presence of comorbidity and age. The annual
      incidence of ARF was 620/million population (pmp), that of advanced ARF 102 pmp.
      The age-related incidence of ARF ranged from 30 pmp in the age group (0-19 years)
      to 4266 pmp in the age group > 80 years. Overall, 22% were referred to a
      nephrologist (34% after excluding those with advanced cancer and age > 80 years).
      Referral of patients decreased from 100% in the age group 0-19 to 5% in those >
      80 years. Referrals in the low-, medium- and high-risk groups were 75%, 30% and
      14%, respectively. Patient survival at 2 years was 80%, 42% and 19% for low-,
      medium-, and high-risk groups, respectively (86%, 44% and 32% for referred
      patients). Referral and outcome in patients with ARF were significantly
      influenced by age and presence of comorbidity at presentation.

PMID- 9536344
TI  - Testosterone and coronary heart disease: is there a link?

PMID- 9536345
TI  - From cosmic chirality to protein structure and function: Lord Kelvin's legacy.

PMID- 9536346
TI  - The life and work of Marshall Hall.

PMID- 9536347
TI  - Percutaneous endoscopic gastrostomies.

PMID- 9536348
TI  - Extra-retinal and perspective cues cause the small range of the induced effect.
AB  - With a horizontal magnifier before one eye, a frontoparallel surface appears
      rotated about a vertical axis (geometric effect). With a vertical magnifier,
      apparent rotation is opposite in direction (induced effect); to restore
      appearance of frontoparallelism, the surface must be rotated away from the
      magnified eye. The induced effect is interesting because it was thought until
      recently that vertical disparities do not play an important role in surface
      perception. As with the geometric effect, the required rotation for the induced
      effect increases linearly to approximately equal to 4% magnification; unlike the
      geometric effect, it plateaus at approximately 8%. Current theory explains the
      linear portion: vertical size ratios (VSRs) are used to compensate for changes in
      horizontal size ratios (HSRs) that accompany eccentric gaze, so changes in VSR
      cause changes in perceived slant. The theory does not explain the plateau. We
      demonstrate that it results from differing slant estimates obtained by use of
      various retinal and extra-retinal signals. When perspective cues to slant are
      minimized or sensed eye position is consistent with VSR, the induced and
      geometric effects have similar magnitudes even at large magnifications.

PMID- 9536349
TI  - Absorption of white light in photoreceptors.
AB  - The fraction F of incident light absorbed by a photoreceptor of length l has
      traditionally been given by F = 1 - e-kl, where k is the absorption coefficient
      of the photoreceptor. Unfortunately, this widely-used expression is incorrect for
      absorption of the type of light most common in natural scenes--broad spectrum
      "white" light--and significantly over-estimates absorption. This is because the
      measured values of k are only valid at the absorbance peak wavelength of
      rhodopsin, whereas at other wavelengths (which the eye may also see) k is lower.
      We have accounted for the wavelength dependence of k and calculated the
      absorption of white light from four different natural radiant sources: the
      quantal irradiances of natural daylight and a patch of very blue sky, and the
      quantal reflections of soil and green foliage irradiated by natural daylight.
      Based on these results, a simple averaged correction for white light stimulation
      is derived, F = kl/(2.3 + kl), which is valid for a wide range of k and l, and
      therefore applicable to both vertebrate and invertebrate photoreceptors.

PMID- 9536350
TI  - Presbyopia and the optical changes in the human crystalline lens with age.
AB  - Lenses from 27 human eyes ranging in age from 10 to 87 years were used to
      determine how accommodation and age affect the optical properties of the lens. A
      scanning laser technique was used to measure focal length and spherical
      aberration of the lenses, while the lenses were subjected to stretching forces
      applied through the ciliary body/zonular complex. The focal length of all
      unstretched lenses increased linearly with increasing age. Younger lenses were
      able to undergo significant changes in focal length with stretching, whereas
      lenses older than 60 years of age showed no changes in focal length with
      stretching. These data provide additional evidence for predominantly lens-based
      theories of presbyopia. Further, these results show that there are substantial
      optical changes in the human lens with increasing age and during accommodation,
      since both the magnitude and the sign of the spherical aberration change with age
      and stretching. These results show that the optical properties of the older
      presbyopic lens are quite different from the younger, accommodated lens.

PMID- 9536351
TI  - Spatial summation in simple (Fourier) and complex (non-Fourier) texture channels.
AB  - Complex (non-Fourier, second-order) channels have been proposed to explain
      aspects of texture-based region segregation and related perceptual tasks. Complex
      channels contain two stages of linear filtering with an intermediate pointwise
      nonlinearity. The intermediate nonlinearity is crucial. Without it, a complex
      channel is equivalent to a single linear filter (a simple channel). Here we asked
      whether the intermediate nonlinearity is piecewise-linear (an ordinary
      rectifier), or compressive, or expansive. We measured the perceptual segregation
      between element-arrangement textures where the contrast and area of the
      individual elements were systematically varied. For solid-square elements, the
      tradeoff between contrast and area was approximately linear, consistent with
      simple linear channels. For Gabor-patch elements, however, the tradeoff was
      highly nonlinear, consistent with complex channels in which the intermediate
      nonlinearity is expansive (with an exponent somewhat higher than 2). Also,
      substantial individual differences in certain details were explainable by
      differential intrusion from "off-frequency" complex channels. Lastly, the results
      reported here (in conjunction with those of other studies) suggest that the
      strongly compressive intensive nonlinearity previously known to act in texture
      segregation cannot be attributed to a compressive nonlinearity acting locally and
      relatively early (before the spatial-frequency and orientation-selective
      channels) but could result from inhibition among the channels (as in a
      normalization network).

PMID- 9536352
TI  - Is human motion detection subserved by a single or multiple channel mechanism?
AB  - Two recent versions of a single channel model of motion perception have had
      impressive success in explaining direction discrimination by human observers for
      spatially filtered noise images in two-flash apparent motion. It has been argued
      that the dramatic breakdown in motion perception which occurs when one image in
      the two-flash sequence is low-pass filtered can be explained only by a single
      channel model. We show that neither version of the single channel model which has
      been proposed can explain performance for noise images chosen to provide
      comparable stimulation in the spatial channels known to subserve human vision. A
      multi-channel model of motion perception has little difficulty in explaining
      these results.

PMID- 9536353
TI  - The effect of white and filtered noise on contrast detection thresholds.
AB  - Models of the dipper effect seen in contrast discrimination experiments predict
      that small amounts of noise should facilitate detection of a subthreshold
      sinusoidal grating. Although facilitation of chromatic sine waves has been
      measured with chromatic or luminance noise, a facilitory effect of luminance
      sinusoidal gratings has not been measured, most likely because the stimulus
      characteristics were not tuned for revealing facilitation. The present study
      measures contrast detection thresholds (CDTs) of sinusoidal gratings in two
      dimensional, static, band-limited white noise and low-pass and high-pass filtered
      noise using a two-interval forced-choice paradigm. The results show facilitation
      in near threshold white noise of middle frequency sinusoidal gratings, and
      facilitation in filtered noise of sinusoidal gratings whose frequency is far
      outside the pass band of the noise. Based on these results, a model of contrast
      detection thresholds is modified such that the facilitation is attributed to
      reduced observer uncertainty caused by small amounts of noise.

PMID- 9536354
TI  - Interaction of stereo vision and optic flow processing revealed by an illusory
      stimulus.
AB  - The influence of stereoscopic vision on the perception of optic flow fields was
      investigated in experiments based on a recently described illusion. In this
      illusion, subjects perceive a shift of the center of an expanding optic flow
      field when it is transparently superimposed by a unidirectional motion pattern.
      This illusory shift can be explained by the visual system taking the presented
      flow pattern as a certain self-motion flow field. Here we examined the dependence
      of the illusory transformation on differences in depth between the two
      superimposed motion patterns. Presenting them with different relative binocular
      disparities, we found a strong variation in the magnitude of the illusory shift.
      Especially when translation was in front of expansion, a highly significant
      decrease of the illusory shift occurred, down to 25% of its magnitude at zero
      disparity. These findings confirm the assumption that the motion pattern is
      interpreted as a self-motion flow field. In a further experiment we presented
      monocular depth cues by changing dot size and dot density. This caused a
      reduction of the illusory shift which is distinctly smaller than under
      stereoscopic presentation. We conclude that the illusory optic flow
      transformation is modified by depth information, especially by binocular
      disparity. The findings are linked to the phenomenon of induced motion and are
      related to neurophysiology.

PMID- 9536355
TI  - A nonlinear chromatic motion mechanism.
AB  - Previous research has demonstrated two categorically distinct mechanisms
      mediating apparent motion of kinematograms composed of eccentricity-confined,
      randomly placed Gabor micropatterns: a quasi-linear mechanism operating for high
      micropattern densities and short time separations, and a nonlinear mechanism
      operating at low micropattern densities or longer time separations. Here we
      compare the performance of these two mechanisms using color (isoluminant) and
      luminance-defined stimuli. When these stimuli are defined only by their color
      contrast, the response of the quasi-linear mechanism is severely impaired, while
      the nonlinear mechanism remains fully operative. This result further strengthens
      the dichotomy between the two kinds of motion perception, and suggests that when
      color vision supports motion perception it does so primarily, or perhaps
      entirely, via a nonlinear mechanism.

PMID- 9536356
TI  - Eye movement control during reading: a simulation of some word-targeting
      strategies.
AB  - McConkie, Kerr, Reddix, & Zola [(1988). Vision Research, 28, 1107-1118]
      demonstrated that the distributions of landing sites on a word tended to be
      gaussian in shape. They provided a detailed account of the behaviour of the eye
      once a target had been selected and a saccade initiated, but said little about
      the process of target selection itself. The purpose of this study was to take as
      a starting point the landing site distributions of McConkie et al., in particular
      the residuals derived from fitting the gaussians to the empirical data, and to
      explore by computer simulation a number of saccade targeting strategies in order
      to discover candidates that best accounted for the residual data. Our results
      indicate that the strategy that gives the best fit involves targeting the longest
      word in a right parafoveal window extending 20 characters to the right of the
      currently fixated word. The implications of this finding for models of reading
      are discussed.

PMID- 9536357
TI  - The area of spatial integration for initial horizontal disparity vergence.
AB  - We investigated over what central area disparity in a random dot stereogram is
      integrated to stimulate an initial vergence response. Vergence was measured
      subjectively, with a forced choice dichoptic nonius vernier task following a
      brief (230 msec) stimulus presentation. Stimuli were random-dot stereograms
      showing a central circular disc of 12.5 min arc crossed retinal disparity in
      front of, and occluding, a same density fixation plane surround. The size of the
      disc was varied. All ten observers responded to the brief stimulus. Initial
      vergence increased with increasing disc diameter and, for nine out of ten
      subjects, reached a maximum with the disc ca 6 deg, suggesting this is the extent
      of the spatial integration region. Below 6 deg diameter, surround and target
      disparities were averaged together. Initial horizontal vergence responds
      automatically to a cyclopean target presented in the centre of gaze by pooling
      disparities within a limited but surprisingly large area.

PMID- 9536358
TI  - The Cyclops effect in adults: sighting without visual feedback.
AB  - When asked to look through a tube, younger children place it at the bridge of the
      nose, and not over one eye: the Cyclops effect. This is a natural response to a
      median plane egocenter. With maturity, the Cyclops effect disappears as we learn
      to overcome the consequences of an egocenter between the two eyes, and instead,
      to use the "preferred" eye. We videotaped adults (n = 14) and children with
      normal vision (n = 30), children with comitant strabismus (n = 14), and adults
      and children (n = 14) with one eye enucleated as they attempted to look through a
      plastic tube. Immediately in front of the face was a liquid crystal window that
      could be either transparent or opaque. As the tube was raised, the window was
      made opaque--blocking sight of the target, their hands, and the tube. Most
      binocular observers placed the tube approximately at the bridge of the nose. This
      was significantly different from the response of the enucleated observers who put
      the tube 75% of the way to the remaining eye (P = 0.0001). All observers align,
      on average, with the measured location of their egocenter when asked to perform a
      monocular task without visual cues. Deprived of visual feedback, binocular
      observers show the Cyclops effect, regardless of age.

PMID- 9536359
TI  - Perceptual learning in visual search: some evidence of specificities.
AB  - To test a recent suggestion that perceptual learning in visual search is non
      specific, two groups of subjects were trained on visual search tasks and tested
      for transfer of learning to new tasks. One group was trained on parallel ("pop
      out") tasks and transferred to serial, conjunction tasks and the other group
      trained on conjunction and transferred to pop-out. Some (not all) tasks which are
      initially serial, rapidly became parallel. Some transfer occurred between the
      different types of tasks. Under some conditions transfer was either absent or
      even negative. The specificities observed may reflect the roles of the brain
      regions involved in learning.

PMID- 9536360
TI  - Feature asymmetries in visual search: effects of display duration, target
      eccentricity, orientation and spatial frequency.
AB  - In Experiments 1-3, we monitored search performance as a function of target
      eccentricity under display durations that either allowed or precluded eye
      movements. The display was present either until observers responded, for 104
      msec, or for 62 msec. In all three experiments an orientation asymmetry emerged:
      observers detected a tilted target among vertical distracters more efficiently
      than a vertical target among vertical distracters. As target eccentricity
      increased, reaction times and errors augmented, and the set size effect became
      more pronounced, more so for vertical than tilted targets. In Experiments 4-7,
      the stimulus spatial properties were manipulated: spatial frequency; size; and
      orientation. The eccentricity effect was more pronounced for vertical than tilted
      targets and for high- than low-spatial frequency targets. This effect was
      eliminated when either the size, the size and orientation, or the size and
      spatial frequency were magnified (M-cortical factor). By increasing the signal-to
      noise ratio, magnification reduced the extent of both asymmetries; it aided more
      the detection of tilted than vertical and of high- than low-spatial frequency
      targets. Experiments 4-7 indicate that performance improvement in the magnified
      conditions was due to the specific pairing of stimulus size with retinal
      eccentricity and not to the larger stimulus size of the magnified conditions. We
      conclude that stimulus size, orientation and spatial frequency influence the
      extent of the eccentricity effect and the efficiency of search performance.

PMID- 9536361
TI  - Limited-capacity mechanisms of visual discrimination.
AB  - Discrimination thresholds of spatial frequency and choice reaction times (RT)
      were measured in three subjects who performed a dual-judgment delayed
      discrimination task. Two reference gratings were presented side-by-side with a 0
      800 msec stimulus onset asynchrony (SOA), which were followed after a 5-sec
      retention interval by two test gratings. Subjects judged which component changed
      and which interval had the higher spatial frequency (SF). Thresholds in the dual
      judgment task were four to six times higher than thresholds in single-judgment
      tasks. The SOA had only a moderate effect on discrimination thresholds, whereas
      the difference between the spatial frequencies of the two components had a highly
      significant effect. The discrimination thresholds increase with increasing
      spatial frequency difference for the lower SF component, while they decrease for
      the higher SF component. An analysis of the distribution of possible error types
      indicated that all subjects tended to respond more frequently that the higher SF
      component changed. This tendency led to more errors on trials where the low SF
      component changed. A posthoc analysis revealed, in two of the three subjects, a
      significant correlation between delta f/f and RT such that higher delta f/f
      values were associated with lower RTs and vice versa.

PMID- 9536362
TI  - Luminance contrast affects motion coherency in plaid patterns by acting as a
      depth-from-occlusion cue.
AB  - Moving plaid patterns composed of component gratings that differ in luminance
      contrast tend not to cohere perceptually. Plaid patterns configured to mimic one
      occlusive grating overlying another also fail to cohere. We hypothesized that
      plaids constructed of components with different luminance contrasts fail to
      cohere because these components are interpreted as occlusive surfaces lying in
      different depth planes. It is known that when depth-from-occlusion and depth-from
      binocular disparity cues support the same depth-ordering, both segregation in
      depth and motion non-coherency are more likely to be perceived than when these
      two cues conflict. We exploited this interaction and tested our hypothesis by
      introducing horizontal binocular disparity between two superimposed component
      gratings of different luminance contrasts. We found that both depth segregation
      and motion non-coherency were much more likely when the high-contrast grating was
      stereoscopically in front of the low-contrast grating. From these results we
      infer that luminance contrast acts as a depth-cue in plaid patterns, with higher
      contrast gratings appearing to lie in front of lower contrast gratings.
      Perceptual motion coherency parallels these depth-ordering judgments. We conclude
      that luminance contrast affects motion coherency by acting as a depth-from
      occlusion cue.

PMID- 9536363
TI  - Sensitivity to second-order motion as a function of temporal frequency and
      eccentricity.
AB  - There is considerable evidence that second-order motion, such as motion
      consisting of a drifting contrast modulation, is detected separately from first
      order motion. Some previous studies have shown that the rate at which sensitivity
      declines as either drift speed or eccentricity increases is the same for both
      types of motion. However, these studies have used second-order motion stimuli
      based on static noise carriers, which we have shown (Smith & Ledgeway, 1997) may
      be inappropriate because they can give rise to local first-order artifacts. By
      using dynamic noise carriers, we isolate the second-order motion mechanism and
      show that its temporal response is much worse than that of the first-order system
      but that its rate of sensitivity loss with increasing stimulus eccentricity is
      indeed similar to that of the first-order motion system.

PMID- 9536364
TI  - Comparison of fixation disparities obtained by objective and subjective methods.
AB  - Fixation disparities (FD) were measured as a function of forced vergence using
      binocular scleral search coils and simultaneously with nonius lines. The slope of
      the objective FD curve was significantly greater than the subjective FD curve for
      three of five subjects. This indicates an alteration in retinal correspondence of
      up to one degree, that shifts Panum's area to avoid the diplopia normally present
      with large disparities. This process allows for fusion in the presence of large
      objective fixation disparities which would normally cause diplopia. The shift in
      correspondence enhances the range of forced vergence, since the larger objective
      FDs serve as more effective stimuli to fusional vergence. The remaining subjects
      who lacked this effect had "flat" FD curves indicative of high vergence
      adaptation.

PMID- 9536365
TI  - Detection facilitation by collinear stimuli in humans: dependence on strength and
      sign of contrast.
AB  - We measured detection of a thin vertical line (target) in the presence of a
      slightly thicker collinear, adjacent line (inducer). Sign and strength of
      contrast of the inducer were varied. Test lines could be either bright or dark.
      Detection thresholds were obtained through a temporal two-alternative forced
      choice (2AFC) procedure with the method of constant stimuli. When target and
      inducer had equal contrast polarity, low thresholds of target lines were observed
      for low inducer contrasts and increased with increasing inducer contrast. With
      opposite contrast polarity of target and inducer, thresholds were high for low
      inducer contrasts and decreased for increasing contrast thereof. Our results
      support the hypothesis that cortical mechanisms with different sensitivity to the
      sign and strength of contrast participate in the detection facilitation of line
      contours.

PMID- 9536366
TI  - Motion assimilation for expansion/contraction and rotation and its spatial
      properties.
AB  - In a two-frame apparent motion display, a test grating was displaced horizontally
      or vertically in the presence of an inducer of which component gratings made up
      expanding/contracting or rotational motion as a whole. In the first experiment,
      we demonstrated that motion assimilation did occur for the test accompanied by
      the two-dimensional motion of the inducer. In the second experiment, we showed
      that the spatial limit of motion assimilation for expansion/contraction or
      rotation was large, extending over at least a visual angle of 14-21 deg in
      diameter, but spatial summation did not occur within the limit. The results were
      discussed in terms of the interaction between local motion detectors and higher
      order detectors which monitor global motion of the whole stimulus pattern.

PMID- 9536367
TI  - Examining edge- and region-based texture analysis mechanisms.
AB  - Instantaneous texture discrimination performance was examined for different
      texture stimuli to uncover the use of edge-based and region-based texture
      analysis mechanisms. Textures were composed of randomly placed, short, oriented
      line segments. Line segment orientation was chosen randomly using a Gaussian
      distribution (described by a mean and a standard deviation). One such
      distribution determined the orientations on the left side of the image, and a
      second distribution was used for the right side. The two textures either abutted
      to form an edge or were separated by a blank region. A texture difference in mean
      orientation led to superior discrimination performance when the textures abutted.
      On the other hand, when the textures differed in the standard deviation of the
      orientation distribution, performance was similar in the two conditions. These
      results suggest that edge-based texture analysis mechanisms were used (i.e. were
      the most sensitive) in the abutting difference-in-mean case, but region-based
      texture analysis mechanisms were used in the other three cases.

PMID- 9536368
TI  - Triphasic temporal impulse responses and Mach bands in time.
AB  - The effect of inducing stimuli on the luminance of a brief test stimulus (2.5'
      wide line) required to match the brightness of a comparison stimulus was measured
      at various stimulus onset asynchronies (SOAs). Assuming that the test brightness
      is determined by the peak response to the test stimulus, the difference in the
      test brightness in the absence and in the presence of an inducing stimulus as a
      function of the SOA was employed as a measure of the temporal response to the
      inducing stimulus. The temporal responses to brief decremental inducing stimuli
      (a 2.5'-wide line and a 30'-wide bar) consisted of three oscillations, the middle
      one being the largest. The triphasic form of the temporal impulse responses was
      confirmed by measuring the temporal step responses to these stimuli. The step
      responses consisted of alternating positive and negative phases which might be
      regarded as a temporal analogue of the Mach bands in space. The data obtained
      were described by a model of the weighting function which was assumed to be a
      spatiotemporal Gabor-like function.

PMID- 9536369
TI  - On the "cyclopean eye": saccadic asymmetry and the reliability of perceived
      straight-ahead.
AB  - If two targets are both on the visual axis of one eye or the other, and binocular
      fixation is shifted from the farther one to the nearer, the aligned eye
      consistently makes an initial, seemingly pointless saccade in a temporal
      direction. The size of those saccades typically differs markedly, depending on
      whether the targets are aligned with the observer's dominant or non-dominant eye.
      Pickwell [(1972) Vision Research, 12, 1499-1507] proposed that this binocular
      asymmetry in oculomotor performance reflects a subject-specific lateral
      displacement of the egocenter (the "binoculus" of Hering, which has traditionally
      been assumed to be on the midline). An empirical test of Pickwell's widely
      endorsed hypothesis has now been conducted and the proposal has been found
      wanting. In an otherwise darkened room, subjects were required repeatedly to set
      a small light to a perceived straight-ahead location in the horizontal plane,
      first for a target at 300 cm distance and then for one at 30 cm. Extrapolation of
      a line that connects the two averages of those settings to the inter-ocular axis
      provides an estimate of the subjective egocenter to which visual directions are
      referred. Contrary to Pickwell's proposal, those locations of the inferred
      egocenter were usually quite near the midline, and were completely uncorrelated
      with same-subject data on the extent of saccadic asymmetry at the onset of
      asymmetrical convergence. The data on perceived straight-ahead underlying this
      result indicate the availability of extraretinal information about eye
      orientation that is quite precise at a given moment (median standard deviation of
      47 min arc) but conspicuously non-stationary over several-minute intervals
      (monotonic drifts in sequential settings being very common).

PMID- 9536370
TI  - Magnocellular visual function and children's single word reading.
AB  - Recent research has shown that reading disabled children find it unusually
      difficult to detect flickering or moving visual stimuli, consistent with impaired
      processing in the magnocellular visual stream. Yet, it remains controversial to
      suggest that reduced visual sensitivity of this kind might affect children's
      reading. Here we suggest that when children read, impaired magnocellular function
      may degrade information about where letters are positioned with respect to each
      other, leading to reading errors which contain sounds not represented in the
      printed word. We call these orthographically inconsistent nonsense errors
      "letter" errors. To test this idea we assessed magnocellular function in a sample
      of 58 unselected children by using a coherent motion detection task. We then gave
      these children a single word reading task and found that their "letter" errors
      were best explained by independent contributions from motion detection (i.e.,
      magnocellular function) and phonological awareness (assessed by a spoonerism
      task). This result held even when chronological age, reading ability, and IQ were
      controlled for. These findings suggest that impaired magnocellular visual
      function, as well as phonological deficits may affect how children read.

PMID- 9536372
TI  - Lines and Gabor functions compared as spatial visual stimuli.
AB  - Foveal discrimination thresholds were measured for orientation, vernier
      alignment, bisection, displacement detection and stereoscopic acuity using simple
      line stimuli and also sinusoidal grating patches with gaussian intensity
      modulation (Gabor stimuli). Stimulus parameters such as luminance, exposure
      duration, component separation and, as far as possible, length were identical for
      both. Orientation discrimination as a function of length is almost identical for
      the two classes of stimuli, some observers performing slightly better with Gabor
      patches. Thresholds for displacement detection are also the same. Vernier, stereo
      and bisection acuities, however, are considerable better with line than with
      Gabor stimuli.

PMID- 9536371
TI  - Rod pigment and rod noise in the European toad Bufo bufo.
AB  - Behavioural experiments and ganglion cell recordings indicate that the visual
      sensitivity of dark-adapted toads is limited by the occurrence of spontaneous
      isomerization-like noise events in the rods. The frequency of these "false
      photons" has previously been studied (with micropipette recording) in the toad
      species Bufo marinus, while the behavioural thresholds were determined using Bufo
      bufo toads. Thus, it was necessary to check that the noise event frequency is
      roughly the same in these two species. Here we show that it is, in both species,
      close to 0.02 events per second and rod (at 22 degrees C). Using
      microspectrophotometry we further show that the absorption spectra of these two
      rhodopsins are very similar, peaking around 503.3 and 501.8 nm for B. marinus and
      B. bufo, respectively.

PMID- 9536373
TI  - Judging distance from ocular convergence.
AB  - Subjects misjudge distances considerably when forced to rely on extra-retinal
      information. Nevertheless, they can reproducibly set a target to the same
      distance as a reference, or to double or half that distance, even when they have
      to look back and forth between them because they are prevented from seeing one
      when looking at the other. Our explanation for this apparent discrepancy is that
      people have access to reasonably accurate extra-retinal information on changes in
      ocular convergence, but can only use this information to judge distances if they
      had reliable information about the orientation of the eyes before the convergence
      changed.

PMID- 9536374
TI  - Accuracy of estimating time to collision using binocular and monocular
      information.
AB  - We measured both the just-noticeable difference in time to collision (TTC) with
      an approaching object, and the absolute accuracy in estimating TTC in the
      following cases: only binocular information available; only monocular information
      available; both binocular and monocular information available as in the everyday
      situation. Observers could discriminate trial-to-trial variations in TTC on the
      basis of binocular information alone: the just-noticeable difference in TTC (5.1
      9.8%) was the same for a small (0.03 deg) target and for a large (0.7 deg)
      target. In line with previous reports, when only monocular information was
      available, the just-noticeable difference in TTC was 5.8-12% for the large
      target. However, observers could not reliably discriminate trial-to-trial
      variations in TTC with the small target when only monocular information was
      available. When both binocular and monocular information was available, the just
      noticeable difference in TTC for the large target was not significantly different
      from when only binocular or only monocular information was available. Observers
      could make reliable estimates of absolute TTC using binocular information only.
      Errors ranged from 2.5 to 10% for the large target, and 2.6 to 3.0% for the small
      target, all being overestimates. Errors for the small target were the same or
      lower than errors for the large target. Observers could make reliable estimates
      of TTC with the large target using monocular information only. Errors ranged from
      2.0 to 12%, all being underestimates. Since monocular information did not provide
      a basis for reliable estimates of absolute TTC with the small target we conclude
      that, in everyday conditions, accurate estimates of TTC with small targets are
      based on binocular information when the object is small and is no more than a few
      metres away. Errors in estimating absolute TTC were lower in the case where both
      binocular and monocular information were available (as in the everyday situation)
      than when only binocular information or only monocular information was available.
      Errors ranged from 1.3 to 2.7%. An error of 1.3% approaches the accuracy required
      to explain the +/- 2.0-2.5 msec accuracy with which top sports players can
      estimate the instant of impact between bat and ball.

PMID- 9536375
TI  - Objective measurement of the off-axis longitudinal chromatic aberration in the
      human eye.
AB  - Longitudinal chromatic aberration (LCA) of the human eye has been studied
      repeatedly, but only at the fovea. Poor visual acuity prevents its subjective
      determination beyond a few degrees eccentricity. Consequently, we have used an
      objective approach, similar to that of Charman and Jennings [(1976). Vision
      Research 16, 999-1005], to measure ocular LCA across the visual field. To
      determine the validity of our double-pass approach, a direct comparison between
      objective and subjective results was established where possible, namely at the
      fovea and parafoveally (2.5 deg). In both cases we focused a monochromatic point
      source at four different wavelengths (458, 501.8, 543.5 and 632.8 nm). At the
      fovea, for a 3 mm pupil, we found a close match between subjective and objective
      results. However, as the subjective task became harder (off-axis or larger
      pupils), subjective results tended to yield slightly more myopic eyes than the
      results for objective refraction. In all cases, the offset was virtually
      independent of the wavelength used. Therefore, we have not found evidence of any
      biased estimates of the LCA, as determined objectively. Our foveal results show
      reasonable agreement with previous findings, except for slightly smaller amounts
      of LCA. Starting at the fovea, LCA tends to gradually increase with eccentricity,
      up to 40 deg, although such an increase is small, just approaching statistical
      significance. Computation of the LCA using a model eye predicts a slightly
      smaller increase with eccentricity.

PMID- 9536376
TI  - Nonlinear combination of luminance excursions during flicker, simultaneous
      contrast, afterimages and binocular fusion.
AB  - The changes in apparent brightness or color, induced into a test spot by a
      surround, can be greatly enhanced either by flickering the test spot between two
      luminances, or by binocularly fusing a pair of test spots of different
      luminances. Simultaneous contrast, in which a white surround makes a grey spot
      look darker, is greatly enhanced if the spot (not the surround) flickers between
      black and white. Colour contrast is likewise enhanced by chromatic flicker: on a
      blue surround, a grey spot looks slightly yellowish, but a yellow/blue flickering
      spot looks strongly yellow. Temporal successive contrasts, or negative
      afterimages, are also enhanced by flickering the test field. The negative
      afterimage of a half-white, half-black rectangle looked dark grey and light grey
      when projected on a grey test field, but it looked almost black and almost white
      when projected on a test field that flickered between black and white. Coloured
      negative afterimages were also enhanced by projecting them on a chromatic
      flickering test field. We examined the combination rules for pairs of luminances
      which were presented either successively as flicker or else dichoptically (and
      fused binocularly). The brightness averaging functions for spatial increments
      (light spots) on dark surrounds were quasi-linear for binocular fusion but
      quadratic for flicker. For spatial decrements (dark spots) on white surrounds,
      the brightness averaging functions were strongly nonlinear winner-take-all for
      both binocular fusion and flicker. We also found temporal analogues of Fechner's
      [(1860). Elements of psychophysics. New York: Holt, Rinehart, Winston, 1966]
      paradox and Levelt's [(1965). British Journal of Psychology, 56, 1-13] dichoptic
      contour effect. We conclude that the visual rules for combining luminance
      excursions, whether in flicker or binocular fusion, favour disproportionately the
      spot with the higher contrast.

PMID- 9536377
TI  - The perceived rigidity of rotating eight-vertex geometric forms: extracting
      nonrigid structure from rigid motion.
AB  - In four experiments, subjects examined four categories of rotating eight-vertex
      geometric forms in parallel projection. Some of the figures appeared to deform,
      even though rigid three-dimensional interpretations were possible mathematically.
      Our results from several deformation-rating tasks indicated that most of the
      configurations maintained a rigid appearance throughout their rotations, although
      one category of stimuli appeared to deform more frequently than the others.
      Configurations from the category that contained a high proportion of stimuli that
      appeared to deform were also shown to be more difficult to discriminate from
      stimuli that had no rigid three-dimensional interpretation (measured using a
      signal detection task). To account for these findings, a theory was formulated
      based on the use of monocular depth cues in the perception of shape. Static
      monocular depth cues we define as those which are present in non-moving stimuli
      and Dynamic monocular depth cues are those that are only present in moving
      stimuli. We conclude that static cues dominate the perception of shape when
      humans respond to parallel (and, most likely, polar) projections of rotating
      objects with rigid three-dimensional interpretations. Further, subjects cannot
      respond to the motion or acceleration profile of part of such a stimulus without
      responding to the figure as a whole.

PMID- 9536378
TI  - Spatial frequency discrimination: visual long-term memory or criterion setting?
AB  - A long-term sensory memory is believed to account for spatial frequency
      discrimination when reference and test stimuli are separated by long intervals.
      We test an alternative proposal: that discrimination is determined by the range
      of test stimuli, through their entrainment of criterion-setting processes.
      Experiments 1 and 2 show that the 50% point of the psychometric function is
      largely determined by the midpoint of the stimulus range, not by the reference
      stimulus. Experiment 3 shows that discrimination of spatial frequencies is
      similarly affected by orthogonal contextual stimuli and parallel contextual
      stimuli and that these effects can be explained by criterion-setting processes.
      These findings support the hypothesis that discrimination over long intervals is
      explained by the operation of criterion-setting processes rather than by long
      term sensory retention of a neural representation of the stimulus.

PMID- 9536379
TI  - Visual motion aftereffects: differential adaptation and test stimulation.
AB  - The local motion adaptation at the basis of the motion aftereffect (MAE) can be
      expressed in a variety of ways, depending upon the structure of the test display
      [Wade et al. (1996). Vision Research, 36, 2167-2175]. Three experiments are
      reported, which examined the characteristics of the test display and of the local
      adaptation process. In Experiment 1, MAEs were recorded in the central of three
      test gratings but their directions depended on the location of the centre
      relative to the adapting gratings. The effects of adapting motions in different
      directions were examined in Experiments 2 and 3, in which one or two adapting
      gratings were presented above or above and below a fixation cross. The upper
      grating always received the same (leftward) direction of motion during
      adaptation, and the lower grating was: moving in the opposite direction,
      stationary, moving in the same direction, or absent. The results indicate that no
      MAE is visible in the upper grating when a single test grating is observed
      experiment 2) and only occurs with two test gratings following differential
      adaptation between the upper and lower gratings (Experiment 3). Thus, the MAE
      occurs as a consequence of adapting restricted retinal regions to motion but it
      can only be expressed when differentially adapted regions are also tested.

PMID- 9536380
TI  - Successive episodes produce direction contrast effects in motion perception.
AB  - Motion coherence thresholds decline with an increase in the number of frames in a
      random dot kinematogram (RDK), indicating that motion information can be
      integrated across successive frames. We investigated whether such temporal
      integration would be disrupted by a brief interval (32-600 msec) inserted into a
      motion sequence, perceptually dividing it into two successive episodes. Both
      episodes consisted of only a few frames (between 3 and 15), with the first
      episode being 100% coherent and the coherence of the second episode being
      adjusted to determine threshold. In four experiments we observed that coherence
      threshold for motion in the second episode was elevated if the directions in the
      two episodes matched, was lowered if they were opposite, and was unaffected if
      they were orthogonal. This successive direction contrast effect did not vary with
      the duration of the interval, suggesting that it is not an adaptation effect. The
      result of varying the number of frames in the second episode suggests that these
      effects are not due to alterations in cooperative activity among motion
      detectors. We suggest that successive direction contrast effects may reflect
      activity of higher-order perceptual organization mechanisms.

PMID- 9536381
TI  - Methodological caveats for monitoring binocular eye position with nonius stimuli.
AB  - Three experiments, using two sets of Nonius lines placed in a random-dot
      stereogram, indicated that Nonius alignment does not always reflect binocular eye
      position and, thus, a caveat is necessary when Nonius alignment is used to
      monitor binocular eye position. We found that: (a) two Nonius lines with visual
      line values that differed by up to 7.6 min of arc can appear aligned; (b) the two
      lines of each of the two Nonius sets continued to appear aligned despite a change
      in vergence angle of 5.9 min of arc; and (c) the Nonius alignment reflected eye
      position better, when the binocular dots near the Nonius lines were eliminated.

PMID- 9536382
TI  - Color vision in two observers with highly biased LWS/MWS cone ratios.
AB  - Two sisters, heterozygous carriers for congenital X-linked protanopia, were
      diagnosed as normal trichromats by the Rayleigh match on the anomaloscope. The
      heterozygous state was established by molecular analysis of their visual pigment
      genes. The normal color match establishes that the spectral sensitivities of
      their long-wavelength-sensitive (LWS) and middle-wavelength-sensitive (MWS) cone
      visual photopigments are within normal variability. Their FM 100-hue test error
      scores were low, demonstrating superior chromatic discrimination. Heterochromatic
      flicker photometric (HEP) spectral sensitivities were like those of protanopes.
      The estimated LWS/MWS cone ratios from the HFP data were 0.09/1 and 0.03/1,
      compared with ratios in the range of 0.6/1 to 10/1 for typical normal
      trichromats. Measurements of chromatic grating acuity on chromatically selective
      backgrounds were performed to study the cone mosaic. The data were consistent
      with a sparsity of LWS cones. Both protan carriers showed normal spectral
      sensitivities for all three cone types under cone isolating chromatic adaptation
      and normal three-peaked curves for increment thresholds on a white pedestal. Hue
      estimation, run on one carrier was normal. The equilibrium yellow locus was
      measured in the other carrier and was in the range of normal trichromats. The
      data indicate that normal color vision can occur even when the LWS/MWS cone ratio
      is quite abnormal.

PMID- 9536383
TI  - Photoreceptor function in unilateral amblyopia.
AB  - We investigated whether photoreceptor function in amblyopic eyes differed from
      that in non-amblyopic eyes. Photoreceptor function was assessed with the optical
      Stiles-Crawford effect (SCE), psychophysical SCE, and foveal visual pigment
      density in both eyes of ten unilateral amblyopic subjects. Optical SCE and
      density measurements were carried out with a custom-built scanning laser
      ophthalmoscope (SLO). Amblyopic and normal eyes did not differ in Stiles-Crawford
      effect, nor in foveal visual pigment density. Contrary to suggestions in the
      literature, we found no indication of retinal dysfunction at the level of the
      cone photoreceptors in amblyopic eyes.

PMID- 9536384
TI  - Long-term reliability and predictive validity of the Teller Acuity Card
      procedure.
AB  - The predictive characteristics of the Teller Acuity Card (TAC) procedure were
      examined in 129 children treated in a neonatal intensive care unit for preterm
      birth or perinatal complications. Monocular TAC grating acuity at 4, 8, 11, 17,
      24, 30, and 36 months was compared with TAC grating acuity (reliability) and HOTV
      recognition acuity (predictive validity) at 48 months. Most reliability
      coefficients were significant, with r's ranging from 0.13 at 17 months to 0.59 at
      36 months. Predictive validity measurements were of similar magnitude, with r's
      ranging from 0.22 at 4 months to 0.61 at 36 months. Normal TAC scores at earlier
      ages were predictive of normal TAC and HOTV acuity at 48 months in 73-95% of
      eyes. TAC scores below the normal range were less predictive, with 39-80% of eyes
      continuing to show below-normal acuity at 48 months.

PMID- 9536385
TI  - Classification of the systemic vasculitides: antineutrophil cytoplasmic
      antibodies, consensus and controversy.

PMID- 9536386
TI  - Development of the anti-ribosomal P autoantibody response.
AB  - OBJECTIVE: Autoantibodies to the ribosomal P phosphoproteins (anti-P) appear
      almost exclusively in SLE. The mechanism by which these autoantibodies appear is
      unknown. The aim of this study was to determine if IgM and IgG isotype switching
      occurs during the development of the anti-P autoantibody response. METHODS:
      Patients who acquired IgG anti-P during clinical observation had their serial
      serum samples from this period screened for IgM and IgG anti-P by immunoblots and
      ELISAs. Rabbits were immunized with the immunodominant peptide of the ribosomal P
      proteins ("P-peptide") cross-linked to bovine serum albumin. Their serial samples
      were also analyzed for IgM and IgG anti-P before and after repeated
      immunizations. RESULTS: Two patients were identified who developed transient low
      titer IgM anti-P that preceded the development of their IgG anti-P. Both patients
      were clinically well during their peak of IgM anti-P, and developed flares of
      disease coincident with their high titered IgG anti-P response. The "P-peptide"
      immunized rabbits developed an IgM anti-P response that preceded IgG anti-P, and
      that decreased over time. CONCLUSION: We conclude that IgM to IgG isotype
      switching occurs in the anti-P autoimmune response. These findings suggest that
      the autoimmune response to the ribosomal P proteins may be antigen-driven.

PMID- 9536387
TI  - Analysis of the NF-kappa B p65 subunit, Fas antigen, Fas ligand and Bcl-2-related
      proteins in the synovium of RA and polyarticular JRA.
AB  - OBJECTIVE: To investigate the nuclear localization of the transcription factor NF
      kappa B, the status of apoptosis and the expression of the Fas antigen, Fas
      ligand, Bcl-2, Bcl-xL and Bax by synovial cells. METHODS: Electrophoresis
      mobility shift assay (EMSA), immunohistochemical staining, two colour-flow
      cytometry and the terminal deoxynucleotidyl transferase (TDT)-mediated dUTP nick
      end labelling (TUNEL)-technique were used. RESULTS: The NF-kappa B p65 subunit
      appears to be present in the nuclei of synovial tissue and fluid cells as
      detected by EMSA and immunohistochemical staining. Fas antigen and Fas ligand (L)
      are expressed on up to 90% and 11% of CD3+ synovial fluid (SF) cells,
      respectively. Both the Fas antigen and its ligand are also expressed by synovial
      tissue cells. Interestingly, freshly isolated SF T cells upregulated the
      expression of Bcl-xL as compared to Bcl-2. An overexpression of Bax compared to
      Bcl-xL was seen in the synovial tissues (ST) of patients with ongoing apoptosis,
      but not in patients with few apoptotic cells. CONCLUSIONS: NF-kappa B appear to
      be activated in vivo, both Fas and its ligand being expressed by synovial cells.
      Apoptosis is ongoing in the ST with significant patient variations. Such
      variations could be in part due to the level of Bax expression. Finally, the
      upregulation of Bcl-xL expression may contribute to the accumulation of SF
      infiltrating T cells.

PMID- 9536388
TI  - Cold-induced coronary Raynaud's phenomenon in patients with systemic sclerosis.
AB  - OBJECTIVE: Cardiac involvement with myocardial-band necrosis is common in
      systemic sclerosis. One possible explanation is that an underlying vasomotor
      abnormality accounts for these histologic findings. To shed light on this issue
      we investigated the existence of "myocardial Raynaud's phenomenon" in such
      patients. METHODS: We examined 25 patients with systemic sclerosis and 14
      patients with systemic lupus erythematosus or rheumatoid arthritis, using cold
      pressor and dipyridamole-thallium-201 scintigraphy. RESULTS: Twenty-three
      patients with systemic sclerosis and 13 patients with lupus erythematosus or
      rheumatoid arthritis had normal perfusion during dipyridamole imaging. Seven
      scleroderma patients with normal dipyridamole test presented cold-induced
      transient myocardial ischemia, while none of the control patients had cold
      induced ischemia (p = 0.034). All patients with cold-induced ischemic defects
      presented long-standing Raynaud's phenomenon (> 5 years); of the 14 patients with
      long-standing Raynaud's phenomenon 7 presented ischemic thallium-201 defects; of
      the remaining 9 patients with Raynaud's phenomenon of short duration (< 5 years)
      none presented cold-induced ischemia (p = 0.019). CONCLUSION: Patients with
      systemic sclerosis and long-standing Raynaud's phenomenon, even in the presence
      of normal myocardial perfusion during pharmacological vasodilation with
      dipyridamole, may present cold-induced myocardial ischemia, a functional
      Raynaud's phenomenon of the heart.

PMID- 9536389
TI  - Tissue concentrations of gastrointestinal regulatory peptides in the duodenal
      mucosa in systemic sclerosis.
AB  - OBJECTIVE: Esophageal hypomotility and abnormalities of intestinal function are
      important manifestations in systemic sclerosis (SSc), but their pathogenesis is
      not well understood. Since there is evidence that plasma concentrations of
      certain gastrointestinal regulatory peptides are increased in SSc, we were
      interested in examining the peptide concentrations and localization in biopsy
      specimens from the intestinal mucosa in SSc patients. We studied 12 patients with
      gastrointestinal disease. METHODS: Levels of corticotrophin-releasing hormone
      (CRH), motilin, neuropeptide Y (NPY) and peptide YY (PYY) were determined by
      radioimmunoassay and high-performance liquid chromatography (HPLC), and the
      occurrence of motilin, PYY, somatostatin, and NPY were studied with
      immunohistochemistry. RESULTS: Except for the concentrations of CRH, which were
      increased 2-fold, the tissue concentration of motilin, NPY and PYY were decreased
      by approximately 50% among patients with esophageal and intestinal dysfunction
      (group B) compared to patients with impaired esophageal motility alone (group A).
      In addition, HPLC-characterization of motilin, NPY, and PYY showed a different
      pattern of fragments among patients in groups A and B. In all patients duodenal
      motilin, PYY, and somatostatin were localized in the endocrine cells. The
      distribution and frequency of the cells did not differ among the patients. NPY
      was localized to neuronal elements; there was no overt difference among the
      patients with respect to the frequency of NPY-containing nerves. CONCLUSION: This
      study shows that patients with widespread gastrointestinal disease have lower
      tissue concentrations of regulatory peptides compared to patients with less
      widespread disease.

PMID- 9536390
TI  - Bindarit prolongs survival and reduces renal damage in NZB/W lupus mice.
AB  - OBJECTIVE: The present study was designed to investigate the effects of bindarit
      on animal survival and renal damage in murine lupus autoimmune disease. METHODS:
      Female NZB/W mice were used. Bindarit was administered, as a 0.5% medicated diet,
      starting either before the onset of the pathology or early in the course of the
      disease, in order to assess the effects of age upon the response. Furthermore,
      the effects of combined administration of bindarit with low dose i.p.
      cyclophosphamide bolus were also studied. Proteinuria and anti-dsDNA antibody
      levels were determined during the course of the study. Renal damage was evaluated
      by light microscopy. RESULTS: Bindarit markedly prolonged the NZB/W mouse life
      span (p < 0.001 vs. controls), showing a significant difference even against high
      dose cyclophosphamide (90 mg/kg ip bolus) chosen as the reference (p < 0.01).
      Bindarit significantly reduced the degree of renal damage, delayed proteinuria
      and did not prevent autoantibody development, thus confirming the lack of
      immunosuppressive activity. CONCLUSION: The present results and other
      experimental data demonstrating the capacity of the drug to interfere with the
      inflammatory and immune response cross-talking, indicate that bindarit exerts its
      action in murine lupus through a novel and original mechanism. These findings,
      coupled with the evidence that the drug possesses a very safe toxicological
      profile, suggest that further investigations to assess the potential value of
      bindarit in the treatment of SLE are warranted.

PMID- 9536391
TI  - A reduced CD8+ lymphocyte subset distinguishes patients with polymyalgia
      rheumatica and temporal arteritis from patients with other diseases.
AB  - OBJECTIVE: To determine the diagnostic and screening test qualities of
      concentrations of the CD8+ lymphocyte subset in peripheral blood to discriminate
      patients with giant cell arteritis (GCA) from patients with other diseases.
      METHODS: A CD8+ lymphocyte test was performed in 454 patients from the Department
      of Medicine, Randers Central Hospital. The sensitivity, specificity and
      predictive values of the test were calculated and presented as receiver operating
      characteristic (ROC) curves. RESULTS: The median percentage and numbers of CD8+
      cells were significantly reduced in 227 patients with active untreated GCA
      compared with 227 in-patients of similar age and sex (GCA vs in-patients CD8% :
      12.0 vs 20.0, CD8+ x 10(9)/l : 0.195 vs 0.374, p < 0.05). Identical ROC curves
      were obtained when patients with GCA were tested against various subgroups of
      patients. The sensitivity and specificity of the test for GCA at an optimal
      cutoff point were 71% and 80%, respectively, while the positive predictive value
      was 80%. CONCLUSION: At an optimal cutoff point, concentrations of the CD8+
      lymphocyte subset in peripheral blood discriminate patients with GCA from
      patients with other diseases. The sensitivity and specificity of the test for GCA
      are equal to those of other tests used in rheumatology.

PMID- 9536392
TI  - Enterobacterial antibodies in Chinese patients with rheumatoid arthritis and
      ankylosing spondylitis.
AB  - OBJECTIVE: To study the role of microbial infection in rheumatic diseases.
      METHODS: Sera from 39 Chinese patients with rheumatoid arthritis (RA), 52
      patients with ankylosing spondylitis (AS) and 51 healthy subjects (HS) were
      examined for IgG, IgA, and IgM class antibodies against Proteus mirabilis,
      Escherichia coli, Campylobacter jejuni, Salmonella typhimurium and enteritidis,
      Yersinia enterocolitica, and Klebsiella pneumoniae (capsular serotypes 31 and
      43), using an enzyme-linked immunosorbent assay. RESULTS: In patients with RA,
      IgA class antibodies against all bacterial strains used as the antigen were
      increased when compared to healthy controls. In patients with AS, significantly
      elevated IgA levels were observed against Campylobacter and Klebsiella K43. IgM
      class antibodies were less frequently elevated in RA and in AS than IgA class
      antibodies. In RA patients, IgG antibodies against Klebsiella K43 and Proteus
      were significantly increased. No differences were observed in IgG class
      antibodies between AS patients and healthy controls. CONCLUSION: Increases in
      serum bacterial antibodies in RA and AS suggest that in both diseases stimulation
      of the intestinal immune system by enterobacteria may have a role. However, the
      question whether this phenomenon is due to increased intestinal permeability
      and/or represents cross reactions between different enterobacteria remains open.

PMID- 9536393
TI  - The inflammatory reaction in giant cell arteritis: an immunohistochemical
      investigation.
AB  - OBJECTIVE: To assess the distribution of the inflammatory reaction in giant cell
      arteritis (GCA). METHODS: Semiquantitative analysis on cryostat sections stained
      with monoclonal antibodies against inflammatory markers. RESULTS: The
      inflammatory infiltration was strongest in the adventitia where it showed sharp
      demarcation along the outer border of the media. The endothelial immunopositivity
      for HLA-DR was strongest in adventitial microvessels. The immunopositivity for
      macrophages, B-cells, HLA-DR, ICAM-1 and IL-2 was significantly stronger in the
      outer than in the inner half of the intima. CONCLUSION: The distribution of
      immunostainings and the crowding of cells seen at the outer media border
      indicates that the majority of the inflammatory cells enter the arterial wall
      from adventitial microvessels, migrate through the media and that the cell
      migration and the inflammatory activity focuses on the peripheral intima/internal
      elastic membrane.

PMID- 9536394
TI  - Cryptococcal meningitis presenting concurrently with systemic lupus
      erythematosus.
AB  - Cryptococcal meningitis is a rare but well recognized complication of systemic
      lupus erythematosus (SLE). Since in all previously reported cases in the medical
      literature the patients developed this opportunistic infection as the result of
      immunosuppressive therapies, whether the intrinsic immunological abnormalities of
      SLE per se contribute to the susceptibility remains controversial. We report on a
      patient who presented concurrently with cryptococcal meningitis and
      cryptococcaemia at the time of her diagnosis of active SLE. This highlights the
      possibility that intrinsic immunological defects of SLE may be directly
      responsible for the predisposition to fungal infections. In addition, when SLE
      patients present with neurological symptoms, the possible presence of central
      nervous system (CNS) infection must be checked for, even if immunosuppressive
      treatment is not being considered.

PMID- 9536395
TI  - Polymyositis associated with asymptomatic primary biliary cirrhosis.
AB  - We here describe a case of polymyositis associated with asymptomatic primary
      biliary cirrhosis and a high titer of antimitochondrial antibodies. The patient
      had remarkable multiorgan engagement: polyarthritis, pericarditis, pleuritis and
      tachyarrythmia. Atypical changes, suggestive of mitochondrial damage, were
      observed in a muscle biopsy specimen. Under treatment with azathioprine and
      steroids, the disease had a favourable outcome.

PMID- 9536396
TI  - HIV infection and SLE: their pathogenic relationship.
AB  - Retroviruses have repeatedly been suggested as a possible trigger mechanism for
      systemic lupus erythematosus (SLE). We review the role of human immunodeficiency
      virus (HIV)-1 envelope glycoprotein (gp120) in the induction of immune
      dysregulation including autoimmunity in HIV-1 infection, and discuss the possible
      relationship between HIV and SLE in the retroviral etiology.

PMID- 9536397
TI  - Oral versus intramuscular methotrexate in juvenile chronic arthritis. Italian
      Pediatric Rheumatology Study Group.
AB  - OBJECTIVE: To compare the efficacy and safety of methotrexate (MTX) after oral
      and intramuscular administration in children with juvenile chronic arthritis
      (JCA). METHODS: Pediatric rheumatology centers in Italy participated in this
      short-term, prospective, open trial. Each investigator was allowed to choose the
      oral or intramuscular route of administration according to his personal
      preference in everyday clinical practice. Patients enrolled by each center were
      given MTX through the same method of administration. All patients received 10
      mg/m2 of MTX each week for six months. RESULTS: A total of 257 patients with JCA
      (127 treated orally and 130 intramuscularly) were enrolled in the trial by 11
      Italian centers. The response rate after 6 months of MTX therapy was 58% in the
      oral and 61% in the intramuscular cohort. The frequency of adverse side effects
      did not differ significantly between the two treatment groups. CONCLUSION: The
      results of this study suggest that MTX at the conventional dose regimen is
      equally effective and has a similar safety profile in children with JCA when
      administered orally or by intramuscular injections.

PMID- 9536398
TI  - Erythromelalgia associated with hypertension and leukocytoclastic vasculitis in a
      child.
AB  - Erythromelalgia is an acrocyanotic rheumatic disease presenting with erythema,
      and pain and a burning sensation in the hands and feet; it is rarely encountered
      during childhood. Hot or warm conditions may precipitate pain and erythema in the
      extremities and the symptoms may regress upon the application of cold water. The
      disease is usually secondary to other systemic diseases in adults. On the other
      hand, it is idiopathic in children. This article describes a case of
      erythromelalgia presenting with leukocytoclastic vasculitis and hypertension in a
      7-year-old child who responded to therapy with prednisolone and phenoxybenzamine.

PMID- 9536399
TI  - Intravenous immunoglobulin therapy in a child with cutaneous polyarteritis
      nodosa.
AB  - Cutaneous polyarteritis nodosa (CPAN) may have a prolonged recurrent course which
      needs chronic corticosteroids treatment to achieve remission. In this report we
      describe a 9 year old boy who developed CPAN, which we treated with high dose
      intravenous immunoglobulin (IVIG), with an immediate favourable response. We
      discuss the advantages of IVIG over corticosteroids and speculate on its
      pathogenesis and mechanism of action.

PMID- 9536400
TI  - Spontaneous liver and kidney hematomas in a 27-year-old male patient with a
      history of juvenile rheumatoid arthritis.

PMID- 9536401
TI  - Pretreatment of skin with a Ginkgo biloba extract/sodium carboxymethyl-beta-1,3
      glucan formulation appears to inhibit the elicitation of allergic contact
      dermatitis in man.
AB  - The clinical efficiency of mitigating contact dermatitis with a Ginkgo biloba
      extract and carboxymethyl-beta-1,3-glucan formulation was investigated in a
      double-blind versus placebo study using 22 subjects (Caucasian women aged 22-55
      years) with allergic contact dermatitis from various substances in the European
      standard series. The formulation was applied to intact skin 2X a day for 2 weeks
      ("in use" application) prior to a single application of a selected contact
      allergen under a Finn Chamber for 24 h. Readings were carried out in a blind
      study by a dermatologist 2 and 3 days after patch removal. Representative
      photographs were taken of treated, placebo and untreated test areas. 68.2% of the
      panelists showed significantly reduced skin reactivity (p = 0.037*) on the
      treated site 2 days after patch removal, versus untreated and/or placebo sites.
      This finding indicates that the Ginkgo biloba/carboxymethyl-beta-1,3-glucan
      formulation can mitigate against allergic contact dermatitis.

PMID- 9536402
TI  - Common contact sensitizers in Chandigarh, India. A study of 200 patients with the
      European standard series.
AB  - 200 patients (122 male, 78 female) with suspected allergic contact dermatitis
      were patch tested with the European standard series (ESS) and the results
      compared with other Asian centres. 131 (65.5%) patients showed 1 or more patch
      test positives to the ESS. Patch tests were positive to all allergens except
      primin. Potassium dichromate was the most common allergen (20.5%) followed by
      nickel sulfate (16.5%), SQL mix (14%), PPD (11.5%), cobalt (8%), fragrance mix
      (7.5%), formaldehyde (6.5%), colophony (5.5%), neomycin sulfate and mercapto mix
      (5% each). In women, nickel sulfate was the commonest allergen (30.8%) followed
      by SQL mix (16.7%) and potassium dichromate (15.4%). In men, potassium dichromate
      was the commonest sensitizer (23.8%) followed by SQL mix and PPD (12.3% each).
      Our results are at variance with other centres in Asia. SQL mix was able to
      detect less than 1/2 (42.2%) of patients allergic to ethanolic dilutions of ether
      extracts of parthenium. We conclude that the European standard series, with
      exclusion of primin, is suitable for detection of allergic contact dermatitis in
      India. However, SQL mix is not a adequate screen for parthenium sensitivity and
      patch testing with extracts of the plant should be continued, wherever indicated.

PMID- 9536403
TI  - Atopy and other risk factors for UK dentists reporting an adverse reaction to
      latex gloves.
AB  - A study was conducted to assess the significance of a personal history of atopy
      and other risk factors for UK dentists reporting an adverse reaction to natural
      rubber latex (NRL) gloves. 2535 dentists completed a self-administered
      questionnaire and, of these, 1034 (group 1) reported an adverse reaction to NRL
      gloves and 1501 (group 2) did not. Risk factors investigated were: sex, years in
      clinical practice, exposure to gloves and a history of atopy or food allergy. The
      signs and symptoms reported by group 1 dentists were recorded. Logistic
      regression analysis was used to identify a set of risk factors that produced the
      most discrete model for a dentist reporting an adverse reaction to NRL gloves. A
      personal history of atopy was a significant risk factor. Dentists with a history
      of eczema and hand eczema in childhood were most likely to report an adverse
      reaction to NRL gloves.

PMID- 9536404
TI  - A controlled study of gold contact hypersensitivity.
AB  - 1203 patients attending for routine patch testing at 3 hospitals and 105
      volunteers were tested with 0.5% and 0.05% gold sodium thiosulfate (GST). 38
      patients (3.2%) and 5 volunteers (4.8%) had positive patch tests to GST. There
      were no significant differences between volunteers and patients with respect to
      age, sex, atopy or exposure to gold in dental restorations, jewellery or through
      occupation. There were no significant differences in prevalence of GST
      hypersensitivity in the 3 hospitals, or between patients and controls. This is
      the 1st controlled study of hypersensitivity to GST, and suggests that routine
      patch testing to gold is of limited clinical benefit.

PMID- 9536405
TI  - Occupational dermatitis in Danish gardeners and greenhouse workers (III).
      Compositae-related symptoms.
AB  - The clinical part of the study aimed at describing epidemiological and diagnostic
      aspects of occupational Compositae dermatitis. Patch testing with the
      sesquiterpene lactone (SL) and Compositae mixes, feverfew extract and
      supplementary allergens in 250 selected gardeners showed Compositae allergy in
      25, 17 females and 8 males. 24 were possibly occupationally sensitized. The mean
      age was lower and the preponderance of women higher compared to classical
      Compositae dermatitis, and the distribution and course of the dermatitis most
      often did not differ from other occupational plant dermatoses. The Compositae mix
      detected 2x as many as the SL mix, and the overall detection rate with both was
      76%, making aimed patch testing necessary. Chrysanthemum (Dendranthema),
      marguerite daisy (Argyranthemum frutescens) and lettuce (Lactuca sativa) were
      frequent sensitizers. Occupational type I allergy to Compositae comprised
      sensitization to Gerbera, chrysanthemum, lettuce, Senecio cruentus and Aster.
      Among 1657 respondents in the questionnaire part of the study, 824 had worked
      with Compositae, and 160 (19%) reported occupational Compositae-related symptoms
      of skin and mucous membranes. Possible risk factors for the development of these
      were assessed in a stepwise logistic regression model and a history of childhood
      eczema, hay fever and duration of exposure were significantly associated with
      Compositae-related irritant and allergic symptoms in both sexes.

PMID- 9536406
TI  - Acute irritation thresholds in subjects with type I--type VI skin.
AB  - It has long been recognized that human skin can be subdivided into simple
      categories based on their sensitivity to sunlight--from Type I, never tans,
      always burns, to Type VI, marked constitutive pigmentation. There is also
      evidence that the more readily sunburnt type of skin is also more susceptible to
      the effect of irritants. In the present work, the irritancy threshold for sodium
      lauryl sulfate (SLS) has been assessed using a recently described 4-h acute skin
      irritation patch test. A total of 110 subjects covering all 6 skin types were
      examined and their threshold for acute irritancy defined as the lowest
      concentration of SLS, applied under 4-h occlusion, which would induce a
      clinically detectable irritant response. The SLS dose response generated using a
      range of concentrations (0.1%-20%) demonstrated that there was no significant
      difference between the groups under these test conditions. Even for Type VI skin
      (n = 25), the dose-response curve fell within the general pattern. These results
      reinforce the general applicability of predictions of acute irritant potential
      made in groups of human volunteers.

PMID- 9536407
TI  - Reliability of diagnostic tests for contact allergy to mydriatic eyedrops.
AB  - Adverse reactions due to the administration of mydriatic eyedrops are not
      uncommon. In Spain, the most commonly used are phenylephrine, tropicamide and
      cyclopentolate hydrochloride. In this study, 37 patients with adverse reactions
      to the administration of mydriatic eyedrops were investigated from January 1993
      to June 1997. The aim was to assess the reliability of the diagnostic methods
      used, particularly the adequate concentration of allergens and the introduction
      of conjunctival challenge as a safe and accurate diagnostic tool in those
      patients who could not be diagnosed by other methods. Phenylephrine was the drug
      most frequently causing sensitization (93.5%) among the 31 allergic patients.
      Preservatives were the cause in only 1. Patch testing detected allergy in 68.5%
      of the subjects. 2 concentrations (1% and 10%) and vehicles (pet. and aq.) were
      used for phenylephrine. The most reliable was 10% aq. Reading at D4 was more
      useful than at D2. The sensitivity of the patch test was low (72.4%) and its
      negative predictive value (NPV) poor (42%). In 24% of patients, allergy to
      phenylephrine was detected only by conjunctival challenge test. This diagnostic
      method is safe and helpful and has not previously been used to diagnose adverse
      reactions due to mydriatic eyedrops.

PMID- 9536408
TI  - Evaluating skin-protective materials against contact irritants and allergens. An
      in vivo screening human model.
AB  - 2 acute irritants and 1 allergen were selected: sodium lauryl sulfate (SLS)
      representative of irritant household and occupational contact dermatitis, the
      combination of ammonium hydroxide (NH4OH) and urea to simulate diaper dermatitis,
      and Rhus to evaluate the effect of model protective materials. The putative
      protective materials and vehicle were applied to both ventral forearms of 10
      subjects in each group, according to a randomized code. Test materials were
      spread over a marked 2.0 cm2 area, massaged in, allowed to dry for 30 min, and
      reapplied with another 30 min drying period. The model irritants and allergen
      were then applied (0.025 ml) to an Al-test occlusive patch, which in turn was
      placed for 24 h over each of the 8 designated sites. Inflammation was scored
      according to a clinical scale 72 h post-application. Paraffin wax plus Acetulan
      in cetyl alcohol, and beeswax plus Acetulan in cetyl alcohol, markedly (p <
      0.001) suppressed SLS irritation. Paraffin wax plus beeswax in cetyl alcohol, and
      Acetulan in cetyl alcohol reduced NH4OH and urea irritation (p < 0.05), paraffin
      wax in cetyl alcohol significantly (p < 0.01) decreasing Rhus allergic contact
      dermatitis. This model, provides an easy approach to screening protectants. Its
      clinical significance requires comparison with an open rather than an occluded
      challenge.

PMID- 9536409
TI  - Prevalence of natural rubber latex allergy (type I and type IV) in laboratory
      workers in The Netherlands.
AB  - The objective of the study was to study the prevalence of Type IV and Type I
      allergy to natural rubber latex (NRL) in a population at risk in the Netherlands.
      Laboratory workers regularly using gloves were invited to complete a
      questionnaire and to be tested. We performed patch tests with standard contact
      allergens, rubber additives, glove powder and pieces of 4 gloves; prick tests
      with inhalant allergens, glove extracts, glove powder and fruit extracts; and
      RASTs. Glove-related hand dermatitis was reported in 36.9% of the individuals
      interviewed. A positive patch test result for rubber additives was seen in only
      6.6%. Glove-related urticaria, rhinoconjunctivitis and/or asthma were reported in
      24.6% of all cases. Confirmation of an IgE-mediated reaction was achieved in 8.3%
      by prick test with glove extracts and 5.0% by RAST. No reaction to glove powder
      was noticed in patch testing or in prick testing. A high prevalence rate of glove
      related symptoms and NRL Type I allergy was found in laboratory workers exposed
      to rubber gloves. Surprisingly, there was no co-existence of Type I and Type IV
      allergy in this population.

PMID- 9536410
TI  - Positive patch test with Kamillosan in a patient with hypersensitivity to
      camomile.

PMID- 9536411
TI  - Allergic contact dermatitis from d-limonene in a laboratory technician.

PMID- 9536412
TI  - An epidemic of isothiazolinone sensitization in a flax spinning mill.

PMID- 9536413
TI  - Occupational allergic dermatoses in hairdressers.

PMID- 9536414
TI  - Positive patch test to cocamidopropyl betaine in a hairdresser.

PMID- 9536415
TI  - A preliminary study of gold sensitization in Singapore.

PMID- 9536416
TI  - Contact urticaria caused by obeche wood (Triplochiton scleroxylon).

PMID- 9536417
TI  - Photodermatitis from non-steroidal anti-inflammatory drugs.

PMID- 9536418
TI  - Simultaneous active sensitization to multiple chemicals.

PMID- 9536419
TI  - Positive patch tests to nigrosine.

PMID- 9536420
TI  - Occupational contact urticaria from cellulase enzyme.

PMID- 9536421
TI  - Chronic urticaria from a dental bridge.

PMID- 9536422
TI  - Allergic contact dermatitis from a neoprene elbow splint.

PMID- 9536423
TI  - Photosensitivity induced by lomefloxacin with cross-photosensitivity to
      ciprofloxacin and fleroxacin.

PMID- 9536424
TI  - Airborne contact dermatitis from Tyrophagus putrescentiae.

PMID- 9536425
TI  - Contact dermatitis in a tracheostomized patient due to a rubber disc.

PMID- 9536426
TI  - Allergic contact dermatitis due to cedarwood oil after dermatoscopy.

PMID- 9536427
TI  - Allergic contact dermatitis from disodium ethylenediamine tetra-acetic acid
      (EDTA) in a local anaesthetic.

PMID- 9536428
TI  - Macular hyperpigmentation in a furnace worker.

PMID- 9536429
TI  - Conformation dependence of MHC class I in the modulation of target cell
      sensitivity to natural killing.
AB  - C1R.Aw68 delta 242 is a human B cell line expressing a mutant class I molecule
      that is defective in assembly and transport at 37 degrees C but is stably
      expressed at room temperature. This cell line has been utilized to study the
      conformation dependence of MHC class I in the modulation of target cell
      sensitivity to natural killing. Surface expression of MHC class I molecules was
      monitored by the antibodies W6/32 (detecting a pan-class I specificity that is
      beta 2-microglobulin and conformation dependent) and HC.10 (detecting free HLA-B
      heavy chain and a subset of HLA-A heavy chains). C1R.Aw68 delta 242 was cultured
      at reduced temperature to induce cell surface expression of class I molecules,
      and then the temperature was shifted to 37 degrees C. During the first 2 h at 37
      degrees C, C1R.Aw68 delta 242 displayed a higher level of HC.10 reactivity than
      W6/32. Conjugation of C1R.Aw68 delta 242 to NK cells correlated inversely with
      W6/32 expression, but not with HC.10 reactivity as revealed by flow cytometry.
      The sensitivity of the C1R.Aw68 delta 242 cells to NK-mediated lysis was also
      examined as a function of temperature, and the level of C1R.Aw68 delta 242
      cytolysis correlated inversely with W6/32 expression but not HC.10. The fact that
      both the conjugation rate and target cell cytolysis increased with decreased
      reactivity with the conformation-dependent antibody W6/32 and not with HC.10, is
      consistent with the hypothesis that NK cell inhibitory receptors (KIR) detect a
      conformation-dependent epitope(s).

PMID- 9536431
TI  - Co-dominant expression of the HLA-G gene and various forms of alternatively
      spliced HLA-G mRNA in human first trimester trophoblast.
AB  - Genes may be silenced at the transcriptional level by 'genomic imprinting' in
      such a way that only one of the parental alleles is expressed. Imprinting may be
      tissue-specific and in some cases it seems also to be time-dependent during
      development. The phenomenon has been studied in pre- and post-implantation
      developmental processes. Animal studies of genomic imprinting of major
      histocompatibility complex (MHC) antigens in the placenta have shown discordant
      results. To address this issue in the human placenta, we examined the expression
      of the non-classical human leukocyte antigen (HLA) class I gene, HLA-G. Genomic
      imprinting of the HLA-G locus could have implications for the interaction in the
      feto-maternal relationship. Restriction Fragment Length Polymorphism (RFLP),
      allele-specific amplification and Single Strand Conformation Polymorphism (SSCP)
      analysis followed by DNA sequencing were performed on Reverse Transcription (RT)
      Polymerase Chain Reaction (PCR) products of HLA-G mRNA to examine the expression
      of maternal and paternal alleles. Our results demonstrate that HLA-G is co
      dominantly expressed in first trimester trophoblast cells. A "new" non-synonymous
      base substitution in exon 4 was detected. We also investigated the different
      alternatively spliced forms of HLA-G mRNA in first trimester trophoblast and
      found the full-length transcript to be the far most abundant.

PMID- 9536430
TI  - Modulation of peptide-dependent allospecific epitopes on HLA-DR4 molecules by HLA
      DM.
AB  - Peptide binding to HLA-DR molecules in intracellular compartments is facilitated
      by HLA-DM molecules, present in most types of antigen-presenting cells.
      Allorecognition of DR specificities represents a form of T cell recognition of
      the MHC-peptide complex which in some cases is influenced by peptide binding. DRA
      and DRB*0401 (Dw4) genes were introduced into different cell types including DM
      negative and DM-restored mutant cells to analyze recognition of DR4 subtypes by
      alloreactive T cell clones and Dw4-specific monoclonal antibodies. Distinct
      patterns of T cell recognition were identified: (i) deficient response to Dw4
      molecules in the absence of DM expression in which T cell responses were restored
      by transfecting DM into the Dw4-expressing cells; and (ii) equivalent recognition
      of Dw4 on DM- and DM+ cells. Using several mAb to Dw4 molecules, a similar
      distinction was observed: a shared epitope on Dw4 and Dw14 molecules was
      partially DM-independent while a Dw4-specific epitope was DM-dependent and cell
      type-specific. Thus, a subset of both T cell and mAb allodeterminants are
      influenced by a DM-dependent interaction of MHC molecules with peptides, while
      the formation of DM-independent allodeterminants may represent direct MHC epitope
      recognition by the T cell receptor or an alternative peptide loading mechanism
      distinct from the HLA-DM pathways.

PMID- 9536432
TI  - In vivo alteration in type-1 and type-2 cytokine balance: a possible mechanism
      for elevated total IgE in HIV-infected patients.
AB  - The progression of HIV infection has been associated with an increase in the
      plasma levels of total IgE. The mechanisms responsible for the increased IgE have
      not been elucidated. The type-1 and type-2 cytokine imbalance associated with HIV
      infection has been proposed as a possible mechanism for elevated IgE. The current
      study was undertaken to investigate the relationship between total IgE, type-1
      and type-2 cytokines from a large HIV+ patient population. HIV+ patients were
      found to have elevated total IgE that inversely correlated with numbers of CD4+ T
      cells. HIV+ plasma was also found to have decreased IFN-gamma and IL-12p70 levels
      as well as increased IL-10 levels compared to HIV-negative individuals. HIV+
      patients with more advanced disease, as defined by absolute CD4+ counts,
      demonstrated more marked differences. Furthermore, the relative ratios of IFN
      gamma:IL-10 and IL-12:IL-10 were decreased in HIV+ patients compared to HIV
      negative individuals. The alterations in the plasma cytokines suggest a switch
      from a predominance of type-1 cytokines to type-2 cytokines that may enhance IgE
      synthesis. These data suggest that measurement of plasma IgE and/or cytokines may
      have prognostic or therapeutic monitoring value in HIV+ patients.

PMID- 9536434
TI  - HLA-DRB4 gene encoded HLA-DR53 specificity segregating with the HLA-DR7, -DQ9
      haplotype: unusual association.
AB  - HLA phenotyping of a leukemia patient of Caucasoid origin revealed the presence
      of the serological HLA-DR53 specificity. Comprehensive pedigree analysis
      demonstrated that the HLA-DR53 specificity segregated with the HLA-DR7, -DQ3
      haplotype. High resolution PCR- SSP genotyping of the HLA class II genes revealed
      the presence of the HLA-DRB4*0101101 allele segregating together with the HLA
      DRB1*0701, -DQA1*0201 and DQB1*03032 alleles. This finding is in contrast to
      known linkages in that thus far, the HLA-DR7, -DQ9 haplotype has only been
      described in association with the non-expressed HLA-DRB4*0103102N allele. The
      existence of this "novel" haplotype may be explained by a homologous
      recombinational event that occurred between the HLA-DR7, -DR53, -DQ2 and the HLA
      DR7, -DQ9 haplotypes.

PMID- 9536433
TI  - The application of human monoclonal antibodies for monitoring donor derived
      soluble HLA class I molecules in the serum of heart transplant recipients.
AB  - Increased levels of both donor and recipient derived HLA molecules can be found
      in serum and plasma of transplanted patients during rejection. Recent data
      suggest that levels of donor specific soluble HLA Class I (sHLA-1) correlate
      better with graft rejection than total sHLA Class I [1, 2]. Therefore,
      quantification of donor specific soluble counterparts of HLA Class I in the serum
      of the recipient may be a new way for non-invasive monitoring of rejection after
      organ transplantation. Up to now, only a limited number of mouse monoclonal
      antibodies (alpha HLA-A2, and alpha HLA-B7) has been used in enzyme linked
      immunosorbent assays (ELISAs) to detect donor specific HLA molecules in the
      plasma of transplant recipients. To monitor other donor-recipient combinations,
      we tested some of our HLA Class I specific human monoclonal antibodies, routinely
      used in complement dependent cytotoxicity, for their suitability in ELISA based
      assays. In the present model system, we used alpha HLA-A9 (BvK5C4) or alpha HLA
      A3 (OK2F3) hybridoma-supernatant to set up a sHLA-A9 and sHLA-A3 specific ELISA.
      In a pilot study we show that these assays were sensitive enough to detect an
      increase of donor specific sHLA-I during rejection in the plasma of two heart
      transplant recipients. Use of a large set of human hybridoma's will enable
      monitoring most recipient/donor combinations in the near future.

PMID- 9536435
TI  - An integrated multiplex-PCR and PCR-RFLP typing system for markers associated
      with seronegative arthritides.
AB  - The system was designed with emphasis on the identification HLA-B alleles and
      genotypes associated or potentially associated with seronegative arthritides. By
      using a combination of multiplex SSP and PCR-RFLPs, the assays can be
      economically performed on a large range of sample sizes in diagnosis and
      epidemiology. 24 HLA-B alleles and subtypes can be discriminated, including
      options for PCR-RFLP or sequence specific amplification of the allele groups B27
      and B60 (B*4001 and B*4007). In addition, the internal control carries central
      MHC polymorphisms, which can help to identify HLA extended halplotypes. False
      negatives, caused by preferential amplification of the internal control under
      suboptimal PCR conditions, were prevented by employing new, optimized PCR buffer.
      Four of the HLA-B primers were pooled into a multiplex reaction whose products
      were subtyped by digestion with seven restriction endonucleases. Specificity and
      sensitivity were verified in a panel of 68 homozygous cell lines and 200
      heterozygous samples. An HLA-B*27-B*40 hybrid allele was observed in 3 out of 95
      B*27-positive individuals from Berlin, Germany. Such an allele could be mistyped
      by some published assays as a B*27/B*40 heterozygote, a genotype reported to
      confer an increased risk for ankylosing spondylitis.

PMID- 9536436
TI  - Nomenclature for factors of the HLA system, update September/October 1997. WHO
      Nomenclature Committee for Factors of the HLA System.

PMID- 9536437
TI  - Nomenclature for factors of the HLA system, update November/December 1997. WHO
      Nomenclature Committee for Factors of the HLA System.

PMID- 9536438
TI  - Cloning of tropomyosins from lobster (Homarus americanus) striated muscles: fast
      and slow isoforms may be generated from the same transcript.
AB  - Complementary DNAs encoding fibre-type-specific isoforms of tropomyosin (Tm) have
      been isolated from lobster (Homarus americanus) striated muscle expression
      libraries made from poly(A)+ RNA purified from deep abdominal (fast-type) and
      crusher-claw closer (slow-type) muscles. A cDNA of slow-muscle Tm (sTm1),
      containing a complete open reading frame (ORF) and portions of the 5' and 3'
      untranslated regions (UTRs), encodes a protein of 284 amino acid residues with a
      predicted mass of 32,950, assuming acetylation of the amino terminus. The
      nucleotide sequence of a fast-muscle tropomyosin (fTm cDNA), which includes the
      entire ORF and part of the 3' UTR, is identical to that of sTm1 cDNA, except in
      the region encoding amino acid residues 39-80 (equivalent to exon 2 of mammalian
      and Drosophila muscle tropomyosin genes). The deduced amino acid sequences, which
      display the heptameric repeats of nonpolar and charged amino acids characteristic
      of alpha-helical coiled-coils, are highly homologous to tropomyosins from rabbit,
      Drosophila, and shrimp (57% to 99% identities, depending on species). Northern
      blot analysis showed that two transcripts (1.1 and 2.1 kb) are present in both
      fibre types. Mass spectrometry indicated that fast muscle contains one major
      isoform (fTm: 32,903), while slow muscle contains two major isoforms (sTm1 and
      sTm2: 32,950 and 32,884 respectively). Both Tm preparations contained minor
      species with a mass of about 32,830. Sequences of peptides derived from purified
      slow and fast Tms were identical to the deduced amino acid sequences of the sTm1
      and fTm cDNAs, respectively, except in the C-terminal region of fTm. The
      difference in mass between that predicted by the deduced sequence (32,880) and
      that measured by mass spectrometry (32,903) suggests that fTm is
      posttranslationally modified, in addition to acetylation of the N-terminal
      methionine. These data are consistent with the hypothesis that the fTm and sTm1
      are generated by alternative splicing of two mutually-exclusive exons near the 5'
      end of the same gene.

PMID- 9536439
TI  - Interaction of troponin-H and glutathione S-transferase-2 in the indirect flight
      muscles of Drosophila melanogaster.
AB  - Drosophila indirect flight muscles (IFMs) contain a 35 kDa protein which cross
      reacts with antibodies to the IFM specific protein troponin-H isoform 34 (TnH
      34). Peptide fingerprinting and peptide sequencing showed that this 35 kDa
      protein is glutathione S-transferase-2 (GST-2). GST-2 is present in the
      asynchronous indirect flight muscles but not in the synchronous tergal depressor
      of the trochanter (jump muscle). Genetic dissection of the sarcomere showed that
      GST-2 is stably associated with the thin filaments but the presence of myosin is
      required to achieve the correct stoichiometry, suggesting that there is also an
      interaction with the thick filament. The two Drosophila TnHs (isoforms 33 and 34)
      are naturally occurring fusion proteins in which a proline-rich extension of
      approximately 250 amino acids replaces the 27 C-terminal residues of the muscle
      specific tropomyosin II isoform. The proteolytic enzyme, Igase, cleaves the
      hydrophobic C-terminal sequence of TnH-34 at three sites and TnH-33 at one site.
      This results in the release of GST-2 from the myofibril. The amount of GST-2
      stably bound to the myofibril is directly proportional to the total amount of
      undigested TnH. It is concluded that GST-2 in the thin filament is stabilized
      there by interaction with TnH. We speculate that the hydrophobic N-terminal
      region of GST-2 interacts with the hydrophobic C-terminal extension of TnH, and
      that both are close to a myosin cross-bridge.

PMID- 9536440
TI  - Molecular characterization of myosin V from Drosophila melanogaster.
AB  - Recent studies have revealed unconventional myosin V to be an important actin
      based molecular motor involved in vesicular movement. In this paper we report the
      molecular characterization of the Drosophila myosin V, identified by reverse
      genetics. The gene encodes a 1792-residue, 207 kDa heavy chain polypeptide which
      possesses a typical head or motor domain of 771 residues, a region of six IQ
      motifs (139 residues) which serve as potential calmodulin/light chain binding
      sites at the head/tail junction, and a tail domain of 882 residues containing
      sequences of putative alpha-helical coiled-coils required for dimerization of the
      molecule and sequences of non-helical structure at the C-terminal end. Based on
      Southern blot analyses and chromosomal localization, evidence is presented for a
      single Drosophila myosin V gene. RNA analyses revealed a doublet of transcripts
      of about 6 kb, expressed throughout the lifetime of a fly but particularly
      abundant in the early stages of embryonic development (maternally contributed),
      in the ectodermic tissue of the hindgut starting at stage 16, and in the adult
      head. These results suggest that myosin V may be involved in processes required
      in a variety of cell types in Drosophila. We have also mapped the Drosophila
      myosin V locus to chromosome 2 at the position 43C-D, and we are currently
      searching for known mutations in this region. Finally, phylogenetic analysis of
      the head domain reveals that Drosophila myosin V is more closely related to
      mammalian myosin Va and Vb than to other invertebrate class-V myosins;
      nevertheless, it is not significantly more related to myosin Va than to myosin
      Vb. While vertebrates would need two different myosin V isoforms to accomplish
      specific functions, we speculate that Drosophila myosin V might provide the
      equivalent functions by itself.

PMID- 9536441
TI  - Effects of myofibrillar bundle diameter on the unloaded shortening velocity of
      skinned skeletal muscle fibres.
AB  - Using both slack tests and force clamp experiments, the velocity of unloaded
      shortening (Vu; Vu(st), slack test; Vu(fc), force clamp) was determined for
      maximally Ca(2+)-activated myofibrillar bundles. These were obtained by
      mechanically splitting single muscle fibres of rat, rabbit, crab and lobster
      skeletal muscles. A comparison was made between the Vu of thick (mammalian: 45-70
      microns mean diameter; crustacean: 90-175 microns) and thin (mammalian: 25-40
      microns; crustacean: 35-85 microns) preparations of the same muscle fibre. The
      bundle diameter had opposite effects on Vu in mammalian and crustacean muscle
      fibres. The Vu of thin mammalian bundles was about 0.6 times that of the thick
      ones, whereas in crustacean preparations this ratio was about 1.5. The kinetics
      of stretch-induced delayed force increase of maximally Ca(2+)-activated fibres
      (stretch activation) appeared not to differ between the thick and thin bundles
      from any animal preparation. Control experiments showed that the observed
      diameter effects on Vu are not due to differences in the chemical environment of
      the myofilaments. One possible explanation is that the intrinsic physical factors
      of the myofibrils modify Vu differently during progressive shortening in
      mammalian and crustacean preparations.

PMID- 9536442
TI  - Protein and mRNA analysis of myosin heavy chains in the developing avian
      pectoralis major muscle.
AB  - While the existence of post-hatch and adult myosin heavy chain isoforms in the
      large, avian type IIB pectoralis major muscle has been clearly established, the
      number and nature of fast myosin heavy chains during in ovo development and the
      perihatch period have not been resolved. In the present study, developmental fast
      heavy chain proteins purified by high resolution anion-exchange have been
      characterized by sequence analysis of a unique CNBr peptide and by complementary
      mRNA analysis. The four proteins present at 15/16 days in ovo are shown to differ
      uniquely in primary structure. They correlate with heavy chains II, IV, VI and
      VII, characterized recently as major or minor species in adult fast muscles using
      similar methods. These four heavy chains are expressed in a time-dependent
      fashion from 8 to 16 days in ovo. At the mRNA level, heavy chain VI predominates
      until 12 days in ovo. Heavy chain IV mRNA is upregulated dramatically at 16 days
      in ovo preparatory to its protein's predominance in the peri-hatch period. Heavy
      chains II, IV and V (the post-hatch isoform which replaces heavy chain IV) have
      major roles in adult fast muscles.

PMID- 9536443
TI  - Skeletal muscle regeneration induced by chorio-allantoic grafting.
AB  - To examine whether the expression pattern of fast-muscle type troponin-T (TnT)
      isoforms was fixed in cell lineage, breast muscle pieces (pectoralis major) from
      chick embryos and young and adult chickens were grafted on to chorio-allantoic
      membrane of 9-day-old chick embryos and cultured until the host embryos hatched
      out. Muscle fibre formation of the grafts was investigated by histological and
      immunohistochemical methods with anti-fast-muscle type and anti-slow-muscle type
      TnT sera, and the expression of fast-muscle type TnT in the grafts from chick
      embryos and young chickens was studied by SDS-polyacrylamide gel electrophoresis
      (SDS-PAGE), two-dimensional SDS-PAGE, and immunoblotting. In the chorio-allantoic
      grafting, the breast muscle initially degenerated forming pyknotic nuclei and
      hyaline cytoplasm. The surviving cells, which were supposed to be satellite
      cells, regenerated new muscle fibres of the same type as those of the grafted
      muscle in respect of TnT isoform expression. Therefore, we considered that the
      ability to express specific isoforms of TnT was fixed in the satellite cells, and
      that chorio-allantoic grafting was a useful technique for studying muscle
      differentiation.

PMID- 9536444
TI  - Rapid recovery following contraction-induced injury to in situ skeletal muscles
      in mdx mice.
AB  - The muscles of mdx mice lack the subsarcolemmal protein dystrophin, and as a
      consequence may be more susceptible to damage induced by contractions. The
      purpose of this study was to characterize the response of muscles in mdx mice to
      contraction-induced injury in situ. The hypothesis tested was that following a
      protocol of repeated stretches of maximally activated muscles, the magnitude of
      the injury is greater for muscles in mdx mice than for muscles in C57BL/10
      control mice, and consequently, the muscles in mdx mice recover more slowly. Each
      stretch was of 20% strain relative to muscle fibre length (Lf) at 0.5 Lf s-1 and
      was initiated from the force plateau of an isometric contraction. The protocol
      consisted of a total of ten contractions, with one contraction occurring every
      ten seconds. The time-course of injury and recovery was determined through
      measurements of in situ force production at 10, 30, 45 and 60 minutes, and either
      12, 24, 48 or 72 hours after the contraction protocol. The initial injury, as
      assessed by the decrease in force production both immediately and 60 minutes
      after the contraction protocol, was significantly greater for the muscles in mdx
      mice compared with those in control mice. Over the next three days, a value for
      maximum isometric force of approximately 80% of the pre-injury value was
      maintained for muscles in control mice, whereas within three days muscles in mdx
      mice showed complete recovery of force. For muscles in mdx mice, the greater
      decrease in force during the contraction protocol and the more rapid recovery
      indicates an increased susceptibility to contraction-induced injury but an
      enhanced rate of recovery.

PMID- 9536446
TI  - Effects of mu opioid agonists alone and in combination with cocaine and D
      amphetamine in rhesus monkeys trained to discriminate cocaine.
AB  - Psychomotor stimulants and mu opioid agonists are often used together by polydrug
      abusers, and it has been suggested that this form of polydrug abuse may result
      from the ability of stimulants and mu agonists to enhance each other's abuse
      related effects. To investigate this possibility, the present study examined
      stimulant-opioid interactions in rhesus monkeys trained to discriminate cocaine.
      Specifically, the effects of the mu opioid agonists heroin, alfentanil, fentanyl,
      and morphine administered alone or in combination with cocaine or d-amphetamine
      were examined in five monkeys trained to discriminate 0.4 mg/kg cocaine (IM) from
      saline in a two-lever, food-reinforced drug discrimination procedure. When
      administered alone, the rapid onset mu agonists heroin (0.032-0.32 mg/kg) and
      alfentanil (0.01-0.1 mg/kg) substituted completely for cocaine in three of five
      monkeys but produced primarily saline-appropriate responding in the other two
      monkeys. The slower onset mu agonists fentanyl (0.0056-0.056 mg/kg) and morphine
      (0.56-10 mg/kg) substituted for cocaine in only one of five monkeys. When
      administered as pretreatments to cocaine, morphine and fentanyl increased levels
      of cocaine-appropriate responding produced by low doses of cocaine in some
      monkeys. Morphine pretreatment also increased levels of cocaine-appropriate
      responding produced by low doses of amphetamine in some monkeys. However, in
      other monkeys, morphine and fentanyl pretreatment did not alter the
      discriminative stimulus effects of cocaine or amphetamine. These results indicate
      that there are substantial individual difference in the effects of mu agonists in
      cocaine-discriminating rhesus monkeys. In some monkeys, mu agonists mimic or
      enhance the discriminative stimulus of cocaine, whereas in other monkeys, mu
      agonists neither mimic nor enhance the effects of stimulants.

PMID- 9536445
TI  - A strain-dependent ratchet model for [phosphate]- and [ATP]-dependent muscle
      contraction.
AB  - A minimal strain-dependent ratchet model of muscle cross-bridge action is
      proposed which is broadly compatible with structural and kinetic constraints. Its
      essential features are: (1) dynamic binding of the S1-products complex to actin
      through a disorder-order transition coupled to the release of inorganic
      phosphate; (2) the absence of a force-generating rotation of the myosin head
      between the two force-holding states A.M.ADP and A.M; (3) strain-control of ADP
      release and ATP binding, giving net isometric tension and directed motility by
      the selective dissociation of negatively strained bound states. With a disordered
      pre-force state, the binding rate to state A.M.ADP need not be symmetric in x,
      the actin site displacement. With faster binding at positive x, the model
      predicts many steady-state and transient properties of striated muscle observed
      experimentally, including phases 2-4 of tension recovery from length changes and
      their dependence on excess phosphate (which enhances and accelerates phase 3) and
      reduced ATP (which gives a bimodal phase 2 and slows one mode). The response to
      large perturbations is often sensitive to the number of actin sites used, and to
      the inclusion of a 1 nm displacement of the neck region on release of ADP. The
      latter stabilizes the periodic tension behaviour produced by repeated releases.

PMID- 9536447
TI  - Effects of hallucinogens on locomotor and investigatory activity and patterns:
      influence of 5-HT2A and 5-HT2C receptors.
AB  - The 5-HT2A and 5-HT2C antagonists MDL 100,907 and SER-082 were tested with the 5
      HT2A/C agonist DOI and the 5-HT1A/2A/2C agonist LSD in the Behavioral Pattern
      Monitor, which provides multiple measures of locomotor and investigatory
      activity. Previous investigations have shown that these measures load onto three
      independent behavioral factors: amount of activity, exploratory behavior, and
      behavioral organization. Rats pretreated with saline, MDL 100,907 (0.25-2.0
      mg/kg), or SER-082 (0.5-1.0 mg/kg) were treated with saline, 0.25 mg/kg DOI, or
      60 micrograms/kg LSD. All effects of DOI were blocked by all doses of MDL
      100,907, but only by the highest dose of SER-082. While the effects of LSD on
      activity and exploratory behavior were largely unaffected, either pretreatment
      antagonized the effects of LSD on behavioral organization. Thus, all of these
      effects of DOI were attributable to 5-HT2A receptors, whereas the effect of LSD
      on behavioral organization was influenced by both 5-HT2A and 5-HT2C receptors.

PMID- 9536449
TI  - Effect of carbamazepine on the single oral dose pharmacokinetics of alprazolam.
AB  - The effect of carbamazepine, an inducer of cytochrome P450 (CYP) 3A4, on the
      single oral dose pharmacokinetics of alprazolam was examined in a double-blind,
      randomized crossover study with two phases. Seven healthy male subjects took
      carbamazepine 300 mg/day or matched placebo orally for 10 days, and on the 8th
      day they took a single oral 0.8 mg dose of alprazolam. Blood samples were taken
      and psychomotor function was assessed by the Digit Symbol Substitution Test,
      Visual Analog Scale, and UKU Side Effect Rating Scale up to 48 h after alprazolam
      dosing. Carbamazepine significantly (p < .01 to .001) decreased the plasma
      alprazolam concentrations during the elimination phase. Carbamazepine
      significantly (p < .001) increased the apparent oral clearance (0.90 +/- 0.21 vs.
      2.13 +/- 0.54 ml/min/kg) and shortened the elimination half-life (17.1 +/- 4.9
      vs. 7.7 +/- 1.7 h), with no significant effect on the peak plasma concentration
      (11.7 +/- 1.5 vs. 13.0 +/- 3.5 ng/ml). The majority of psychomotor function
      parameters during the carbamazepine treatment were not significantly different
      from those during the placebo treatment, probably because of the sedative effect
      of carbamazepine itself. The present study suggests that carbamazepine decreases
      plasma concentration of alprazolam by inducing its metabolism. It also supports
      the previous studies, suggesting that alprazolam is metabolized predominantly by
      CYP3A4.

PMID- 9536448
TI  - Response of the ventral pallidal/mediodorsal thalamic system to antipsychotic
      drug administration: involvement of the prefrontal cortex.
AB  - Intracellular recordings were obtained from rat ventral pallidal (VP) and
      mediodorsal thalamic (MD) cells in vivo and the effects of antipsychotic drugs on
      their basal and evoked electrophysiological characteristics were assessed.
      Administration of either haloperidol or clozapine caused a significant decrease
      in the average firing rate, accompanied by a hyperpolarization of the membrane
      potential in the VP cells recorded. However, neither drug induced a substantial
      change in the other basic membrane properties of the MD cells or VP cells tested.
      In addition, in 50% of the MD cells tested, both antipsychotic drugs caused a
      change in spike discharge from an oscillatory pattern to a tonic discharge mode.
      In rats that had received ibotenic acid lesions of the prefrontal cortex (PFCtx)
      4-8 weeks prior to recording, cells in the VP exhibited similar changes in firing
      frequency in response to haloperidol administration as those in the intact rats.
      However, in contrast to the intact rats, MD cells recorded from rats with PFCtx
      lesions exhibited a significant increase in firing rate after haloperidol
      administration. The results from this study suggest that the prefrontal cortex
      plays a role in modulating the response of the thalamus to antipsychotic drugs.

PMID- 9536450
TI  - Divalproex sodium attenuates growth hormone response to baclofen in healthy human
      males.
AB  - The effect of divalproex sodium (DVP) on gamma-aminobutyric acid-B (GABAB)
      receptor function in humans was assessed by measuring growth hormone (GH)
      responses to a challenge with a GABAB receptor agonist, baclofen, in 10 male
      healthy volunteers. Each subject received 20 mg of baclofen at 10:00 A.M., and
      blood samples were collected for measuring GH before and 30, 60, 90, 120, 150,
      180 min after baclofen administration. The baclofen challenge test was repeated
      after 1 week of treatment with DVP (1000 mg/day). The results showed that the
      plasma GH response to baclofen was significantly attenuated by the DVP treatment
      and that the degree of attenuation was positively correlated with the blood
      levels of valproic acid. Our findings suggest that DVP downregulates hypothalamic
      GABAB receptor function in humans.

PMID- 9536451
TI  - Demonstration of dose-dependent global and regional cocaine-induced reductions in
      brain blood flow using a novel approach to quantitative single photon emission
      computerized tomography.
AB  - Ischemic stroke is a common cause of morbidity and mortality in cocaine addicts.
      Because the previous semiquantitative single photon emission computerized
      tomography (SPECT) method for measuring brain blood flow does not quantify blood
      flow, the magnitude and specificity of cocaine's effects during drug taking has
      not been well established. Here, using a novel quantitative approach to SPECT, we
      established that intravenous cocaine administration to nine recently abstinent
      cocaine-dependent subjects was associated with significant decreases in global
      and regional brain blood flow to dopamine-rich areas such as the prefrontal,
      frontal temporal, and subcortical gray matter. Establishing the utility of this
      relatively new quantitative SPECT technique provides an important tool for the
      management of vascular disorders of the brain. Additionally, identifying the site
      specific effects of cocaine provides targets for the development of putative
      therapeutic medications to attenuate or minimize ischemic stroke in cocaine
      addicts.

PMID- 9536452
TI  - Repeated low-level formaldehyde exposure produces cross-sensitization to cocaine:
      possible relevance to chemical sensitivity in humans.
AB  - Sensitivity to chemicals in humans has been proposed to be an acquired disorder
      in which individuals become increasingly sensitive to chemicals in the
      environment. A possible link between the manifestation of psychiatric symptoms in
      individuals claiming sensitivity to chemicals was investigated based on a leading
      hypothesis put forth by Bell and co-workers (1992) to explain the amplification
      of symptoms after chemical exposure. The hypothesis is that chemical
      sensitivities may be akin to sensitization observed in rodents after repeated
      psychostimulants. Repeated exposure to psychostimulants enhances behavioral
      activity and the underlying neurochemical responses in specific limbic pathways;
      a similar sensitization of limbic pathways has been proposed to occur in
      individuals who become sensitive to chemicals. To test this hypothesis, female
      Sprague-Dawley rats were exposed to either air or formaldehyde (Form) for 1 h/day
      for 7 days or 20 days (5 days/week x 4 weeks). Two to 4 days after the last
      exposure, rats were given a cocaine challenge (= early withdrawal) followed by an
      additional cocaine challenge 4-6 weeks later (= late withdrawal). No differences
      in cocaine-induced locomotor activity were noted between groups after 7 days of
      exposure. However, after 20 days of exposure to Form, vertical activity was
      significantly elevated at both early and late withdrawal times. These studies
      demonstrate that behavioral sensitization occurs after long-term, but not short
      term, low-level exposure to Form, and lends support to the limbic system
      sensitization hypothesis of sensitivity to chemicals in humans.

PMID- 9536453
TI  - Agonist and antagonist actions of (-)pindolol at recombinant, human serotonin1A
      (5-HT1A) receptors.
AB  - It has been proposed that the arylalkylamine, (-)pindolol, potentiates the
      therapeutic action of antidepressant drugs in humans by blockade of 5-HT1A
      autoreceptors. Its interactions at human 5-HT1A receptors have not, however, been
      directly characterized. Herein, we demonstrate that (-)pindolol exhibits
      nanomolar affinity at human 5-HT1A receptors expressed in Chinese Hamster Ovary
      cells (CHO-h5-HT1A; Ki = 6.4 nmol/L). In a functional test of receptor-mediated G
      protein activation (stimulation of [35S]-GTP gamma S binding) (-)pindolol
      displays an efficacy of 20.3% relative to the endogenous agonist, 5-HT (= 100%).
      (-)Pindolol also antagonizes 5-HT (100 nmol/L)-stimulated [35S]-GTP gamma S
      binding, reducing it to 19.8% of control binding. These data indicate that (
      )pindolol acts as a (weak) partial agonist at CHO-h5-HT1A receptors and that it
      blocks the action of 5-HT at these sites.

PMID- 9536454
TI  - Reversal of haloperidol-induced extrapyramidal side effects in cebus monkeys by 8
      hydroxy-2-(di-n-propylamino)tetralin and its enantiomers.
AB  - (+/-)-8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), (+)-8-OH-DPAT, and (-)
      8-OH-DPAT produced dose-related reversals of haloperidol-induced extrapyramidal
      side effects (EPS) in cebus monkeys, with all compounds producing similar almost
      complete reversals at 0.1 mg/kg i.m. These compounds were more potent than
      apomorphine, which reversed haloperidol-induced EPS at 0.3, but not 0.1, mg/kg
      i.m. The data indicate that the reversal of haloperidol-induced EPS by (+/-)-8-OH
      DPAT and its enantiomers is mediated via effects at 5-HT1A receptors, not
      dopamine D2 receptors. Thus, inclusion of 5-HT1A agonist activity in novel
      antipsychotics may reduce EPS liability.

PMID- 9536455
TI  - Baclofen as a cocaine anti-craving medication: a preliminary clinical study.

PMID- 9536456
TI  - Drug free schizophrenics and stage IV sleep.

PMID- 9536457
TI  - Effects of chronic, low-level organophosphate exposure on delayed recall,
      discrimination, and spatial learning in monkeys and rats.
AB  - Chronic exposure to low levels of organophosphate (OP) compounds impairs
      acetylcholine (ACh) degradation by acetylcholinesterase (AChE) and, in humans,
      may produce lasting neurotoxicity affecting cognitive function. The present
      studies examined the ability of such exposure to impair performance of well
      learned cognitive tasks in two species, nonhuman primates and rats. During 25
      days of exposure to a 0.01 mg/kg dose of the OP diisopropylfluorophosphate (DFP),
      mature adult monkeys were not impaired in their performance of a well-learned
      delayed matching-to-sample task (DMTS). However, erythrocyte AChE activity was
      reduced from predrug levels by 76.26 +/- 3.33% by 14 days after the initiation of
      DFP administration. Following titration of DFP to a 0.015 mg/kg dose for 15 days,
      DMTS performance remained at or above baseline levels. DMTS accuracy was
      moderately, but not significantly, reduced after titration to a dose of 0.02
      mg/kg. However, decrements were associated with mild, overt symptoms of OP
      toxicity and performance returned to baseline levels after withdrawal from OP
      exposure. In rats, chronic exposure to a low-dose regimen of DFP (0.25 mg/kg/day
      for 14 days) impaired the ability to initially learn a spatial navigation task,
      but did not impair performance of previously learned stimulus discrimination and
      spatial navigation tasks. These data indicate that performance of memory tasks
      dependent upon reference concepts is not impaired by OP exposure regimens that
      impair acquisition of novel cognitive tasks prior to the onset of overt toxicity.

PMID- 9536458
TI  - Learning/memory impairments in rat offspring prenatally exposed to phenytoin.
AB  - Phenytoin (PHT) was orally administered in dosages of 50 and 100 mg/kg/day to
      pregnant rats on days 7-18 of gestation. Offspring were tested on the negative
      geotaxis test, a figure-eight maze (F8), the Biel water maze (BM), the Morris
      maze (MM), and the radial maze (RM). In addition, a delayed nonmatching-to-sample
      (DNMTS) test was employed. The levels of neuropeptides in brain and brain weights
      were determined. The maturation of negative geotaxis was delayed in both PHT
      groups. PHT groups showed no differences in F8, BM, and MM. In the RM, the total
      number of choices was high, whereas the number of correct choices was low. In the
      DNMTS, PHT groups showed low for correct choices with a long interval. The
      concentrations of neuropeptides were changed in the mesolimbic cortex,
      hippocampus, and amygdala. Brain weights were lower at 6 weeks of age in the 100
      mg/kg/day PHT group, but were comparable at 16 weeks of age. This study suggests
      that the RM is a detectable task for the learning/memory impairments induced by
      PHT. In addition, it is surmised that the learning deficit is due to a working
      memory impairment arising from abnormal changes in neuropeptides and an injury in
      the fetal hippocampus.

PMID- 9536459
TI  - Preweaning cocaine administration alters the adult response to quipazine:
      comparison with fluoxetine.
AB  - This study investigated whether exposure to cocaine during the preweaning period
      affects the behavioral response to administration of a challenge dose of
      quipazine, a relatively nonselective serotonin (5-HT) mixed agonist/antagonist,
      in adulthood. To determine whether selective inhibition of the 5-HT transporter
      during the preweaning period would produce a cocaine-like pattern of effects,
      another group of rats was given fluoxetine, a highly selective and potent
      inhibitor of the 5-HT transporter, and was tested along with the cocaine-treated
      rats. Male and female rats received 25 mg/kg cocaine HCl (82.5 mumol/kg), 25
      mg/kg fluoxetine HCl (72.3 mumol/kg), or vehicle subcutaneous (s.c.) during
      postnatal days 11-20. Both treatments reduced weight gain during the injection
      period only. At 60 days of age, subjects were administered a single dose of
      quipazine (0, 0.4, or 1.0 mg/kg, s.c.) and placed in the Accuscan activity
      monitor for 1 h of behavioral recording. Overall, distance traveled, vertical
      activity, and time in the center of the chamber decreased during the initial time
      blocks of the session and vertical activity decreased with increasing doses of
      quipazine. Females in general showed greater overall activity levels than males
      as well as greater responsivity to quipazine. Preweaning cocaine exposure
      produced different effects in males and females. In males, cocaine enhanced the
      response to quipazine for vertical activity whereas it had no effect on quipazine
      induced alterations on the other two behaviors. On the other hand, cocaine
      treated females showed dampened dose-related quipazine responses across all
      behavioral measures. Fluoxetine administration produced a dampening of the
      quipazine effect for vertical activity and distance traveled in males and
      females. Therefore, these data indicate that cocaine administration during the
      preweaning period of development produced an increase in the effect of a
      serotonergic drug to alter vertical activity in males and a global dampening of
      the behavioral responses to that same drug in females. Preweaning fluoxetine
      treatment produced effects that resembled those produced by cocaine in females, a
      dampening of serotonergic responsivity, along with an overall decrease in
      locomotor activity. Because the majority of effects are seen during the initial
      portion of the behavioral session, a time of heightened activity in response to a
      novel environment, the data suggest that inhibition of the 5-HT transporter
      during the preweaning period alters serotonergic influences over novelty-induced
      activity but that brief periods of inhibition or other actions of cocaine, such
      as those at the catecholamine transporters, prevent this from happening,
      particularly in males.

PMID- 9536460
TI  - Schedule-controlled operant behavior of rats during 1,1,1-trichloroethane
      inhalation: relationship to blood and brain solvent concentrations.
AB  - The central nervous system is the principal target of 1,1,1-trichloroethane
      (TRI), and several studies of this volatile solvent have demonstrated effects on
      learned animal behaviors. There have been few attempts, however, to
      quantitatively relate such effects to blood or target organ (brain) solvent
      concentrations. Therefore, Sprague-Dawley rats trained to lever-press for
      evaporated milk on a variable interval 30-s reinforcement schedule were placed in
      an operant test cage and exposed to clean air for 20 min, followed by a single
      concentration of TRI vapor (500-5000 ppm) for 100 min. Additional rats were
      exposed to equivalent TRI concentrations for 10, 20, 40, 60, 80, or 100 min to
      determine blood and brain concentration vs. time profiles. Inhalation of 1000 ppm
      slightly increased operant response rates, whereas 2000, 3500, and 5000 ppm
      decreased operant response rates in a concentration- and time-dependent manner.
      Accumulation of TRI in blood and brain was rapid and concentration dependent,
      with the brain concentration roughly twice that of blood. Plots of blood and
      brain TRI concentrations against operant performance showed responding in excess
      of control rates at low concentrations, and decreasing response rates as
      concentrations increased. Linear regression analyses indicated that blood and
      brain concentrations, as well as measures of time integrals of internal dose,
      were strongly correlated with operant performance. Neurobehavioral toxicity in
      laboratory animals, as measured by changes in operant performance, can therefore
      be quantitatively related to internal measures of TRI exposure to enhance its
      predictive value for human risk assessment.

PMID- 9536461
TI  - Modulation of monoamine oxidase activity in different brain regions and platelets
      following exposure of rats to methylmercury.
AB  - Monoamine oxidase (MAO; EC 1.4.3.4) is known to have an important role in the
      regulation of biogenic amines in the brain and peripheral tissues. It is also
      known that circulating platelets represent an excellent model for an easy
      assessment of the effect of MAO-B inhibitors in extracerebral tissue. The present
      study was carried out to determine the effects of methylmercury (MeHg) on the
      activity of MAO in synaptosomes of different brain regions of male Sprague-Dawley
      rats as well as in rat blood platelets both in vitro and in vivo. MeHg
      pretreatment inhibited the activity of MAO in the synaptosomes of the cortex,
      hypothalamus, hippocampus, striatum, cerebellum, and brain stem in a
      concentration-dependent (0-10 microM) manner. The threshold concentration of MeHg
      for such inhibition in different brain synaptosomes was found to be the same
      (i.e., 1 microM) except for in the rat striatum it was 2.5 microM, and the IC50
      value for MeHg was found to be around 2.1 microM. Significant inhibition of the
      MAO activity was also observed in synaptosomes of the cortex, cerebellum,
      hypothalamus, and hippocampus as well as in platelets of rats 24 h after
      treatment by gavage with a total cumulative dose of 35 mg/kg (5 mg/kg/day for 7
      days). The decrease of such activity was found to be at maximum in different
      brain synaptosomes and platelets 24 h following treatment with a cumulative total
      dose of 75 mg/kg (7.5 mg/kg/day for 10 days); the treated animals showed signs of
      ataxia under these conditions. The data have further shown that methylmercury is
      capable of inhibiting the MAO activity in different brain synaptosomes to
      different degrees but without showing any specificity towards any specific brain
      region. The present in vivo results suggest that the platelet MAO activity may be
      used as a potential biomarker of early neurotoxicity due to repeated exposure to
      MeHg in rats.

PMID- 9536462
TI  - A method for adjusting exposure levels of volatile solvents based on effects on
      schedule-controlled behavior.
AB  - A novel adjusting procedure was employed to assess the acute behavioral effects
      of inhaled 1,1,1-trichloroethane (TCE) and m-xylene. Mice were trained to lever
      press under a fixed ratio 20 schedule of milk reinforcement. During 30-min test
      sessions, TCE concentrations were altered every 5 min dependent upon rates of
      responding in the preceding 5-min segment of the session. When response rates
      during a 5-min interval were not decreased by greater than 30% from control
      rates, the TCE concentration for the next interval was increased. Reduction in
      response rates of more than 30% from the previous interval resulted in a lowering
      of the TCE concentration in the subsequent 5-min interval. TCE produced
      concentration-dependent decreases in response rates similar to what has been
      shown previously and many mice adjusted their exposure levels such that there
      were alternating intervals of increasing and decreasing concentration exposures.
      This provided a means of determining, in a single test session, no effect
      (subthreshold) and minimal effect concentrations of TCE for effects on schedule
      controlled behavior. Alteration of the starting TCE concentration from 1000 to
      6000 ppm increased the TCE threshold for effects. When the response rate
      contingency was removed and TCE concentrations were "played back" from an earlier
      adjustment session, concentration-effect curves were similar to what were
      obtained under adjusting conditions. Using the adjusting procedure, we were also
      able to rapidly obtain a concentration-effect curve and threshold concentrations
      for m-xylene that are consistent with published results. This procedure for
      response rate adjusting exposure concentrations should be useful for rapid
      assessment of inhalant effects on schedule-controlled behavior and for focusing
      attention on near threshold levels of exposure.

PMID- 9536463
TI  - Neurochemical and neurobehavioral effects of neonatal administration of beta-N
      methylamino-L-alanine and 3,3'-iminodipropionitrile.
AB  - Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease
      that is characterized by a loss of motor neurons in the spinal cord, brain stem,
      and cortex. The present study examined the neurochemical and neurobehavioral
      consequences of the neonatal administration of IDPN and BMAA, two neurotoxins
      previously considered as experimental models of ALS. Sprague-Dawley rat pups
      (male and female) were injected SC with IDPN or BMAA. The following treatment
      groups (n = 5-14 per group) were studied; IDPN [100 mg/kg on postnatal days
      (PNDs) 2, 4, and 6], BMAA-A (500 mg/kg PND 5 only), BMAA-B (500 mg/kg PND 2 and
      5), and BMAA-C (100 mg/kg PND 2 and 5). Neurobehavioral testing was performed and
      the rats were sacrificed at 101 days of age. Monoamine and amino acid content was
      measured by HPLC in brain regions and the spinal cord. IDPN treatment impaired
      the righting reflex and decreased forepaw suspension times. BMAA-A and BMAA-B
      males exhibited an increase in open field behavior. The hindlimb splay of BMAA-A
      females was increased. Other significant behavioral and endocrine effects were
      also seen with neonatal IDPN or BMAA treatment. IDPN females had increased spinal
      cord content of norepinephrine (NE), serotonin, and 5-hydroxyindoleacetic acid (5
      HIAA). IDPN males had no alterations in spinal cord content of NE or Glu, but
      serotonin and 5-HIAA content were increased. BMAA-A and BMAA-B males also had
      elevated spinal cord 5-HIAA content whereas females were unaffected. Glu and Asp
      content in the spinal cord was elevated in the female BMAA-C group. Monoamines
      were also altered in the cerebellum, mediobasal hypothalamus, and hippocampus by
      IDPN and BMAA treatment. alpha 2-Adrenergic binding sites were increased in the
      spinal cord by IDPN and in the cerebellum by BMAA treatment. The results of this
      study clearly demonstrated that both IDPN and BMAA given neonatally can produce
      changes in motor function and spinal cord neurochemistry, although the pattern of
      the effects is both treatment and sex dependent. Neonatal exposure to either IDPN
      or BMAA resulted in permanent changes in adult neurochemistry that may be related
      to reorganizational effects induced by toxin-mediated neuroplasticity in
      developing neurons.

PMID- 9536464
TI  - Heart rate orienting and respiratory sinus arrhythmia development in rats exposed
      to alcohol or hypoxia.
AB  - The effect of alcohol exposure and hypoxia on the heart rate orienting response
      and RSA development was studied in preweanling rats. Rats were artificially
      reared from postnatal days 4 through 12 and either exposed to alcohol (5
      g/kg/day) or hypoxia (two 15-min episodes/day) from postnatal days 4 to 10.
      Control groups consisted of artificially reared and normally reared rats not
      exposed to alcohol or hypoxia. The heart rate and respiration was recorded at
      baseline and during repeated exposures to auditory and visual stimuli every other
      day from postnatal day 13 through 21. The hypoxia group showed an enhanced heart
      rate orienting response to the auditory stimuli on postnatal days 17 and 19
      compared to the other three groups, which did not differ from each other. The
      baseline interbeat interval increased over this period of time and there was a
      large increase in respiratory sinus arrhythmia from postnatal day 15 to 21. The
      alcohol and hypoxia rats showed significantly less of an increase in respiratory
      sinus arrhythmia on postnatal days 19 and 21. All rats showed a greater response
      to the auditory stimuli than to the visual stimuli on postnatal days 17 and 19
      and all groups showed equivalent habituation to both stimuli within a session.
      The results suggest that respiratory sinus arrhythmia and the heart rate response
      to stimuli may not be strongly related during this developmental stage in the rat
      and that hypoxia but not alcohol exposure alters attentional processes for
      auditory stimuli as measured by the heart rate orienting response.

PMID- 9536465
TI  - Effects of the neurotoxin 3,3'-iminodipropionitrile on acoustic startle and
      locomotor activity in rats: a comparison of functional observational and
      automated startle assessment methods.
AB  - Iminodipropionitrile (IDPN) is a neurotoxin that has been used in the validation
      of the U.S. Environmental Protection Agency's Functional Observational Battery
      (FOB), including acoustic startle. We compared the FOB clicker startle method to
      an automated procedure. IDPN was administered IP to male Long-Evans rats in three
      daily doses of 0, 100, 200, or 400 mg/kg (N = 8 per group). There was a
      significant effect of IDPN on clicker startle that was attributable to reduced
      startle in the IDPN-400 group. There were multiple significant effects of IDPN on
      automated startle. The overall effect of IDPN on automated startle was to reduce
      startle amplitude in the IDPN-400 and -200 groups. In addition, the IDPN-400
      group showed startle reductions on all days, whereas the IDPN-200 group showed
      reduced startle primarily on day 1. IDPN also significantly altered locomotor
      activity, which was included as an internal check on IDPN's efficacy. The typical
      pattern of hypolocomotion was found on day 2 posttreatment in the IDPN-400 and 
      200 groups, followed by hyperlocomotion on all subsequent days in the IDPN-400
      group. The startle results demonstrated that automated startle is more sensitive
      (at least for IDPN treatment), eliminates observer judgments, and provides
      interval-scaled data compared to the clicker method. However, automated startle
      also requires additional initial cost and more testing time per animal when
      multiple trials are presented.

PMID- 9536466
TI  - The eradication treatments of Helicobacter pylori.
AB  - The eradication of Helicobacter pylori is at present widely recognized as the
      adequate therapeutic approach for gastric and duodenal ulcers in infected
      patients. In those with dyspepsia but no ulcer as well as in those with type B
      chronic gastritis, eradication remains controversial. It is difficult to have a
      clear opinion on the advantages and disadvantages of the numerous existing
      therapies. Therefore, a systematic review of published treatments has been made
      by the authors. Ideally, the eradication treatment of H. pylori should have the
      following advantages: 1. eradication superior to 90%, 2. simplicity, 3. short
      duration, 4. safety, 5. low cost, 6. reproducibility of results. Dual therapies
      (2 antibiotics or a proton pump inhibitor in combination with an antibiotic)
      rarely allow an eradication greater than 90% and the results have poor
      reproducibility. Consequently, they do not represent an ideal anti-H. pylori
      treatment. Triple therapies come closer to the requirements for an ideal
      treatment, with eradication rates generally close to 90%, varying little between
      studies and the countries in which they were performed. The triple therapy
      bismuth-imidazole-tetracycline (or amoxicillin) still represents for many authors
      the standard reference therapy. It has the advantage of low cost, high efficacy
      and widespread use. It is the therapy that has been the most studied. However,
      the increasing emergence of strains resistant to imidazoles, the complexity of
      the treatment (10 to 12 tablets per day), the numerous adverse effects and the
      lack of availability of bismuth salts in certain countries has led to the
      elaboration of therapeutic schemes combining an antisecretory drug with 2
      antibiotics. Among these, the combination PPI-clarithromycine-imidazole during 7
      days represents the most studied triple therapy of short duration for some
      authors, it already represents a new standard. However, the efficacy of this
      therapy seems dependent on the sensitivity of the bacteria to imidazoles.
      Consequently, this combination cannot be considered as the ideal anti-H. pylori
      treatment in the areas where the prevalence of strains resistant to imidazoles is
      high. The association PPI-clarithromycine-amoxicillin appears on the contrary to
      be very effective against strains resistant to metronidazole and therefore could
      constitute the treatment of choice in population with high prevalence of such
      strains. Great hope is currently surrounding the finalization of a vaccine
      directed against the urease of the bacteria. This approach would allow both the
      treatment and the prevention of Helicobacter pylori infection on a large scale.

PMID- 9536467
TI  - Melatonin and its physiological and therapeutic properties.
AB  - Melatonin is a hormone produced mainly by the pineal gland in most vertebrate
      species, including humans. Recent metabolic, receptor and functional studies
      created a picture of the melatoninergic system(s) in living organisms, its
      organization, physiology and a role in some pathologic conditions. The melatonin
      generating system is characterized by three basic features: (1) photosensitivity,
      (2) diurnal (or circadian) rhythmicity (with highest levels of melatonin
      production occurring at night in darkness), and (3) age-related decline in its
      activity. Cyclic nocturnal increases of melatonin levels are proportional to the
      length of nights (or dark periods of an imposed light-dark cycle); the hormone
      thus conveys a photoperiodic message, and functions in an organism as an internal
      biochemical clock and calendar. Biological actions of melatonin are mediated via
      specific melatonin receptors, whose distribution in the body is uneven, yet with
      decisively highest density in the suprachiasmatic nuclei of the hypothalamus,
      pars tuberalis of the pituitary, and the retina (particularly in birds and lower
      vertebrates). Such a distribution of melatonin receptors suggests that the
      principal physiological role of the hormone is related to both chronobiology and
      modulation of the body hormonal milieu. This review surveys recent developments
      in the melatonin field, and summarizes current knowledge on the melatoninergic
      mechanisms, including the therapeutic aspect related to the hormone.

PMID- 9536468
TI  - Monitoring of TPN consumption at the University Teaching Hospital in Hradec
      Kralove.
AB  - To standardize studies on the utilization and consumption of drugs, the World
      Health Organization recommends the use of the Anatomical Therapeutic Chemical
      (ATC) classification system, using the defined daily dose (DDD value) as a
      technical unit of measurement of drug consumption. DDD values of total parenteral
      nutrition have not been established yet. In our descriptive study the methodology
      by E. Frankfort et al. (1993) is used. This methodology allows the calculation of
      both the total number of DDD values for TPN and the number of DDD values for the
      individual substances. Suggested DDD values and consumption of total parenteral
      nutrition by E. Frankfort et al. (1994) were compared with the values at the
      Teaching Hospital in Hradec Kralove. During 3 months 142 patients administered
      only TPN were included in the study. The following data from every patient were
      collected: sex, age, the main diagnosis, composition of TPN each day and duration
      of this administration. The mean PDD value for carbohydrates was 200 +/- 41 g,
      for fat emulsion 77 +/- 27 g and for amino acids 93 +/- 16 g. The difference
      between our and Frankfort's results were found.

PMID- 9536469
TI  - Evaluation of a filling system for binary pediatric solutions.
AB  - The aim of this study was to assess the use of an automatic filling system
      (Siframix M31 and M32 system) to prepare pediatric parenteral nutrition.
      Volumetric accuracy was measured for each siframix system loads cells (< 5% for 5
      ml with the Siframix M32 and < 5% for 9 ml with the Siframix M31) with sterile
      water for injection. The minimal 20 ml of flushing sterile water of the common
      tubulure of the Siframix M32 (p = 0.211 for 20 ml and p = 0.75 for 500 ml), the
      use of viscous solutions (70% dextrose) on the Siframix M31 (p = 0.28 for 20 ml
      and p = 0.12 for 500 ml) and the use of a special tubulure for using E.V.A. Luer
      lock bags (p = 0.89 for 20 ml and p = 0.103 for 500 ml) do not modify the
      accuracy. Changing bags or bottles during the filling operation modify the
      accuracy (p = 0.004 for 20 ml and p = 0.009 for 500 ml). A flushing operation is
      necessary to lower the risk of electrolytic pollution for the filling of little
      bags. The filling speed for each module was also measured (the maximal filling
      speed was five liters per minute). The Siframix system allows one to prepare
      pediatric parenteral nutrition bags when volumes are above 4 ml and with adapted
      source solutions in terms of concentration and conditioning volumes.

PMID- 9536470
TI  - The ICPC coding system in pharmacy: developing a subset, ICPC-Ph.
AB  - The ICPC system is a coding system developed for general medical practice, to be
      able to code the GP-patient encounters and other actions. Some of the codes can
      be easily used by community pharmacists to code complaints and diseases in
      pharmaceutical care practice. We developed a subset of the ICPC codes for
      community pharmacists. This article describes the method used and the resulting
      ICPC-Ph list.

PMID- 9536471
TI  - Acute hepatitis in a patient using a Chinese herbal tea--a case report.
AB  - A case is presented of reversible acute hepatitis in a patient using a Chinese
      herbal tea. Upon identification of the tea mixture Aristolochia species,
      including A. debilis, which contains the highly toxic aristolochic acid, could be
      identified. We conclude that the acute hepatitis as described in this patient is
      most likely to be caused by (one of) the active ingredients of the Chinese herbal
      tea. Furthermore, this case illustrates that so-called natural products can cause
      unexpected severe adverse reactions.

PMID- 9536472
TI  - The relationship between insight, illness and treatment outcome in schizophrenia.
AB  - Lack of awareness of mental disorder in schizophrenia has been increasingly
      identified by researchers during recent years due to a resurgence of interest in
      the subject. In addition, better measurement methods have led to more valid and
      detailed investigations on insight in schizophrenia. Poor insight has been
      reported as a common phenomenon which may have both nosological and prognostic
      value. Specifically, due to recent studies indicating that lack of insight in
      schizophrenia may lead to poor treatment outcome, research focused on this
      phenomenon could lead to increasingly effective and efficient treatment
      strategies. However, many past and present studies reporting a correlation
      between insight and outcome in schizophrenia demonstrate significant theoretical
      or methodological limitations which may limit the implications and generalization
      of findings. This article lists and critically analyzes historical and
      contemporary research focusing on insight, illness, and outcome in schizophrenia.
      The role of insight is outlined, as are current methods for assessing awareness
      of mental disorder in schizophrenia. Cumulative research in this area is then
      reviewed, in terms of hypotheses, methods, conclusions, and limitations. Finally,
      suggestions for future research in this area are delineated.

PMID- 9536473
TI  - Cognitive-behavioral therapy for panic: effectiveness and limitations.
AB  - The cognitive model of panic and cognitive-behavioral therapy were evaluated. It
      was argued that the cognitive model is not clear about the definition of threat,
      and that panic is evoked by the fear of the dissolution of the self. Furthermore,
      panic attacks will not lead to panic disorder unless the individual is
      experiencing general anxiety and is concerned with his/her physical or mental
      state. Controlled studies have demonstrated that cognitive-behavioral therapy is
      superior to other treatments for panic--85% of patients are panic-free at
      posttreatment and improvements are maintained at follow-up. However, 26% of
      waiting-list controls are also panic-free making the net percentage of panic-free
      treated patients 59%. There is room for improvement in at least 50% of patients,
      and a substantial number of patients continue to take medication and seek
      additional treatment. There is a need to determine the essential components of
      cognitive-behavioral therapy. It was predicted that exposure will prove to be the
      most crucial component. Exposure to phobic situations and interoceptive cues
      should be extended to the underlying causes of panic disorder, such as concerns
      with identity and dependency needs.

PMID- 9536474
TI  - A comparison of staff and patient perceptions of the causes and cures of physical
      aggression on a psychiatric unit.
AB  - OBJECTIVE: The purpose of the study was to compare staff versus patient
      perceptions of the causes and emotional impact of verbal and physical aggression
      on a psychiatric inpatient unit, and the corrective measures each group would
      endorse. METHODS: Fifty-four patients and 32 nursing staff members responded to
      similar questions about physical and verbal aggression. They also reported their
      emotional responses to aggression and steps they would endorse to reduce
      aggression at the medical center. Data was analyzed by chi-square tests for
      proportion comparisons between groups. RESULTS: "Verbal Abuse" was viewed an
      important contributor to physical aggression. Staff stressed patient substance
      abuse and violent lifestyles. Patients focused on the use of involuntary
      procedures and cultural differences between patients and staff. CONCLUSIONS:
      Patients endorsed more restrictive safety measures as long as the measures such
      as metal detectors and searches were applied to staff and visitors, as well as
      patients. Patients requested more input into decision-making processes through
      patient-staff workgroups.

PMID- 9536475
TI  - Public-academic liaison research centers in an era of managed care.
AB  - Public-Academic Liaison research centers (PALs) have traditionally provided
      benefits to both state mental health authorities (SMHAs) and academic
      institutions. The advent of managed care, austere state fiscal budgets, and a
      restructured national research development capacity suggests the need for new
      administrative approaches to PAL research efforts to maintain these benefits in
      this era of rapidly changing health care. This brief report outlines one such
      approach by the Massachusetts SMHA in its efforts to establish two PAL research
      centers: one for clinical neuroscience, and one for behavioral and forensic
      science. Preliminary two-year outcomes are presented, and the implications of the
      model are discussed.

PMID- 9536476
TI  - Creatine kinase elevations and aggressive behavior in hospitalized forensic
      patients.
AB  - The relationship between creatine kinase (CK) and aggressive behavior was tested
      in 195 males consecutively admitted to a forensic hospital. Among patients
      receiving antipsychotic medication, the most violent patients had higher CK
      levels than less violent patients. This was not the case in patients who did not
      receive antipsychotic medication. CK levels were not influenced by age,
      ethnicity, or clinical diagnosis. CK levels were however influenced by prior
      assaultiveness and restraints. When these two factors were controlled for, CK
      levels remained strongly associated with subsequent violence. CK appears to be a
      potential predictor of violent behavior. It has the advantage of easy
      availability in comparison to other biological markers of aggression (e.g., 5
      HIAA). Prospective studies are needed to confirm the validity of this
      biobehavioral association.

PMID- 9536477
TI  - Ultrafast contrast-enhanced three-dimensional MR angiography: state of the art.
AB  - Ultrafast breath-hold contrast material-enhanced magnetic resonance (MR)
      angiography can be performed with a flexible imaging sequence. With the current
      generation of high-speed imaging gradients, it is possible to achieve sequence
      repetition times of 4 msec or less. These repetition times make it possible to
      obtain high-resolution (512 x 512 x 64) images in under 30 seconds. Applications
      of this versatile technique include imaging of aortic dissection, thoracic and
      abdominal aortic aneurysm, pulmonary embolus, carotid stenosis, and peripheral
      vascular disease. The administration of contrast material must be tailored to the
      vascular anatomy under examination to avoid venous enhancement. The rapid data
      acquisition times can be used to image multiple temporal phases or multiple
      locations. With this technique and administration of a T1-shortening contrast
      agent, high-quality MR angiography can be routinely performed in a variety of
      vascular regions (eg, thoracic and abdominal aorta, pulmonary arteries, carotid
      arteries, lower extremities).

PMID- 9536478
TI  - Thoracic MR aortography: imaging techniques and strategies.
AB  - Three-dimensional (3D) gadolinium-enhanced magnetic resonance (MR) angiography is
      a promising technique for thoracic aortography that complements
      electrocardiographically gated T1-weighted spin-echo imaging and cine MR imaging.
      Axial and left anterior oblique T1-weighted spin-echo images are well suited to
      measurement of aortic dimensions and evaluation of aortic aneurysms. Sagittal and
      coronal spin-echo images are helpful in evaluation of vascular rings and aortic
      dissection. Cine gradient-echo and cine phase-contrast imaging allow dynamic
      evaluation of aortic and valvular flow. Cine phase-contrast imaging also enables
      noninvasive quantification of blood flow. Capable of being performed during a
      single breath hold, 3D gadolinium-enhanced MR angiography provides high
      resolution 3D data that can be readily used for projection angiography and
      multiplanar reformation. This technique enables further demonstration of subtle
      pathologic conditions. Three-dimensional gadolinium-enhanced MR angiography
      allows more comprehensive and efficient evaluation of the thoracic aorta.

PMID- 9536479
TI  - How many cheeks must we turn?

PMID- 9536480
TI  - Percutaneous vertebroplasty: state of the art.
AB  - Vertebroplasty is an effective new radiologic procedure consisting of the
      percutaneous injection of a biomaterial, usually methyl methacrylate, into a
      lesion of a vertebral body. This technique allows marked or complete pain relief
      and bone strengthening in most cases. The principal indications for
      vertebroplasty are osteolytic metastasis and myeloma, painful or aggressive
      hemangioma, and osteoporotic vertebral collapse with debilitating pain that
      persists despite correct medical treatment. Radiography and computed tomography
      must be performed in the days preceding vertebroplasty to assess the extent of
      vertebral collapse, the location and extent of the lytic process, the visibility
      and degree of involvement of the pedicles, the presence of cortical destruction
      or fracture, and the presence of epidural or foraminal stenosis caused by tumor
      extension or bone fragment retropulsion. Leakage of methyl methacrylate during
      vertebroplasty may cause compression of adjacent structures and necessitate
      emergency decompressive surgery; thus, the procedure should be performed only in
      a surgical center. The decision to perform vertebroplasty should be made by a
      multidisciplinary team because the choice between vertebroplasty, surgery,
      radiation therapy, medical treatment, or a combination thereof depends on a
      number of factors. Radiologists need to be aware of the various indications for
      vertebroplasty and of potential future developments and applications of the
      procedure.

PMID- 9536481
TI  - US of the ankle: technique, anatomy, and diagnosis of pathologic conditions.
AB  - For specific indications, ultrasound (US) is an efficient and inexpensive
      alternative to magnetic resonance (MR) imaging for evaluation of the ankle. In
      addition to the tendons and tendon sheaths, other ankle structures demonstrated
      with US include the anterior joint space, retrocalcaneal bursa, ligaments, and
      plantar fascia. Ankle US allows detection of tenosynovitis and tendinitis, as
      well as partial and complete tendon tears. Joint effusions, intraarticular
      bodies, ganglion cysts, ligamentous tears, and plantar fasciitis can also be
      diagnosed. As pressure for cost containment continues, demand for US of the ankle
      may increase given its lower cost compared with that of MR imaging. In most
      cases, a focused ankle US examination can be performed more rapidly and
      efficiently than MR imaging. Familiarity with the technique of ankle US, normal
      US anatomy, and the US appearances of pathologic conditions will establish the
      role of US as an effective method of imaging the ankle.

PMID- 9536482
TI  - Pediatric skeletal scintigraphy: applications of pinhole magnification.
AB  - Pinhole magnification scintigraphy is an effective means of evaluating the
      pediatric skeleton because it provides optimal high-resolution images. This
      technique is indicated when diagnostic uncertainty persists after high-resolution
      imaging with parallel hole collimation. Pinhole magnification scintigraphy
      requires approximately 20 minutes of acquisition time per image and meticulous
      attention to details such as choice of pinhole insert, collimator positioning,
      and patient immobilization. However, the technique is superior to planar imaging
      in demonstrating acute osteomyelitis in bone adjacent to growth centers and
      epiphyseal involvement that is either primary or the result of local spread of
      infection. In addition, pinhole imaging has proved highly reliable in the early
      diagnosis of Legg-Calve-Perthes disease and is useful in depicting osteonecrosis
      related to specific causes such as corticosteroid treatment or trauma.
      Scintigraphic manifestations of femoral head ischemia or infarction and findings
      indicative of osteomyelitis associated with a hip effusion are well demonstrated
      with pinhole imaging. This technique also helps characterize osteoid osteomas and
      may be used intraoperatively to confirm the complete excision of this benign
      tumor. Finally, pinhole magnification scintigraphy clearly depicts fractures of
      the femoral neck and allows a high degree of confidence in diagnosing injuries to
      the small bones of the hands and feet.

PMID- 9536483
TI  - Reversible intracerebral pathologic entities mediated by vascular autoregulatory
      dysfunction.
AB  - Several cerebral pathologic processes thought to result from derangements in
      vascular autoregulatory mechanisms show reversible abnormalities on computed
      tomographic and magnetic resonance images. The hypertensive encephalopathies are
      characterized by intracranial abnormalities due to subacutely elevated blood
      pressure; these entities include hypertensive encephalopathy, preeclampsia and
      eclampsia, and cyclosporine toxicity. Imaging studies reveal symmetric confluent
      lesions with mild mass effect and patchy enhancement centered in the immediate
      subcortical white matter of the occipital lobes. The uremic encephalopathies are
      characterized by intracranial abnormalities due to an elevated level of blood
      urea nitrogen; these entities include uremia and glomerulonephritis, hemolytic
      uremic syndrome, and thrombotic thrombocytopenic purpura. Imaging studies reveal
      multiple areas of symmetric edema in the basal ganglia; in severe cases, focal
      infarcts with or without hemorrhage can be seen. As radiologists become more
      familiar with these entities, cases can be recognized earlier in the disease
      process, allowing more timely initiation of appropriate therapy.

PMID- 9536484
TI  - CT characteristics of metastatic disease of the pancreas.
AB  - Contrast material-enhanced computed tomographic (CT) scans obtained over a 10
      year period in 66 patients with metastases to the pancreas were retrospectively
      reviewed. The primary tumors most commonly responsible for these metastases were
      renal cell carcinoma (30.3%) and bronchogenic carcinoma (22.7%). Metastases
      showed no predilection for any particular part of the pancreas. The majority
      (75.8%) of metastases appeared as tumors with discrete margins, and most of these
      tumors were round or ovoid with smooth borders. Over three-fourths of the lesions
      demonstrated enhancement (usually heterogeneous). Vascular involvement was
      uncommon. In those patients in whom pancreatic metastases were discovered some
      time after the primary tumor was identified, the interval ranged from 2 to 295
      months, with the longest mean interval (120.2 months) being associated with
      metastatic tumors from renal cell carcinoma. The appearance of these tumors at CT
      -predominantly hyperattenuating masses, often with nonenhancing internal
      components--was similar to that of primary renal cell carcinoma. In most
      pancreatic metastases, however, clinical information in conjunction with CT
      characteristics such as multiplicity of tumors or hypervascularity permit
      differentiation of metastases from primary neoplasm. When diagnosis of a
      pancreatic neoplasm is uncertain, percutaneous biopsy often permits histologic
      confirmation of the tumor type.

PMID- 9536485
TI  - CT evaluation of small bowel neoplasms: spectrum of disease.
AB  - Neoplasms of the small bowel are rare lesions that account for less than 5% of
      all gastrointestinal tumors. Although the differential diagnosis for a small
      bowel tumor is extensive, various small bowel neoplasms have characteristic
      features at computed tomography (CT) that may aid in making a diagnosis. Small
      bowel adenocarcinoma may appear at CT as an annular lesion, a discrete nodular
      mass, or an ulcerative lesion. Non-Hodgkin lymphoma may appear as a segmental
      bulky mass that gradually merges into the normal bowel wall. Lymphoma is
      characteristically associated with marked luminal dilatation. Carcinoid tumor may
      appear as an ill-defined homogeneous mass that displaces bowel loops.
      Calcification and desmoplastic reaction in a mesenteric mass suggest the
      diagnosis of carcinoid tumor. Gastrointestinal stromal tumors (GISTs), both
      benign and malignant, may be submucosal, subserosal, or intraluminal. The CT
      appearance of a GIST may include a sharply defined mass with homogeneous
      attenuation, sometimes with calcification. Lipoma appears at CT as a well
      circumscribed, intraluminal homogeneous mass with fat attenuation. Most malignant
      small bowel tumors are actually metastases that have spread intraperitoneally,
      hematogenously, or by local extension. Intraperitoneal seeding usually manifests
      at CT as multiple small nodular metastases along the small bowel serosa,
      mesentery, and omentum. In patients with Peutz-Jeghers syndrome, nonneoplastic
      lesions may mimic small bowel neoplasms.

PMID- 9536486
TI  - Spectrum of CT findings in nonmalignant disease of the adrenal gland.
AB  - Computed tomography (CT) plays a leading role in the evaluation of nonmalignant
      disease of the adrenal gland. CT is highly accurate in the localization of
      adrenal masses in patients with diseases associated with hyperfunctioning adrenal
      glands such as Cushing syndrome and Cushing disease, Conn syndrome, adrenal
      tumors leading to virilization or feminization, and pheochromocytomas. CT permits
      a specific diagnosis of acute or subacute adrenal hematoma and myelolipoma.
      Hematomas are round to oval and have increased attenuation (50-90 HU) that
      decreases on follow-up CT scans. Myelolipomas typically manifest as a well
      defined suprarenal mass with an attenuation of-30 to -115 HU. Adrenal cysts are
      usually round to oval and manifest as a hypoattenuating mass with a smooth, thin
      wall. CT is useful in the evaluation of patients with Addison disease,
      particularly the subacute form secondary to tuberculosis or disseminated
      histoplasmosis. Findings typically include bilateral adrenal enlargement with a
      central necrotic area of hypoattenuation and peripheral enhancement. Thin-section
      unenhanced CT permits accurate measurement of attenuation and can be used to
      differentiate adrenal adenoma from metastasis in a cancer patient with an
      indeterminate mass: Attenuation of 10 HU or less usually indicates adenoma rather
      than cancer. If the mass is found incidentally at contrast material-enhanced CT,
      delayed scans obtained as early as 5-15 minutes after intravenous administration
      of contrast material appear to have comparable accuracy.

PMID- 9536487
TI  - Imaging of the umbilicus and periumbilical region.
AB  - Umbilical disorders can be classified according to embryonic remnants contained
      in the umbilicus, including the urachus, omphalomesenteric duct, and round
      ligament of the liver; the extraperitoneal paravesical spaces; the umbilical
      ring; and the umbilicus itself. Only one of the five types of congenital urachal
      abnormalities (urachal cyst) is common. All anomalies associated with the
      omphalomesenteric duct are rare except the Meckel diverticulum, which is the most
      common congenital abnormality of the gastrointestinal tract. The round ligament
      contains the remnant of the umbilical vein, which in the presence of portal
      hypertension, may open, recanalize, and form a portosystemic collateral vessel.
      Extraperitoneal paravesical spaces that run from the umbilicus to the bladder may
      contain fluid collections. The umbilical ring and the umbilicus may give rise to
      many masses, including omphalocele, gastroschisis, various hernias, inflammatory
      and suppurative processes, and neoplasms. Clinical manifestations of umbilical
      disorders are usually nonspecific; use of cross-sectional imaging can help
      identify most of these entities because of their typical locations and
      distributions in continuity with the urinary bladder and the umbilicus and guide
      therapy. Understanding the anatomy and the differential diagnosis of umbilical
      disorders is key to arriving at a correct diagnosis and proper patient treatment.

PMID- 9536488
TI  - From the Archives of the AFIP. Mucinous cystic neoplasms of the pancreas:
      radiologic-pathologic correlation.
AB  - Mucinous cystic neoplasms of the pancreas are rare primary tumors. They have
      pathologic and clinical similarities to biliary cystadenomas of the liver and
      mucinous cystic tumors of the ovary. Mucinous cystic neoplasms of the pancreas
      typically affect middle-aged women and arise in the tail of the pancreas. Gross
      pathologic and imaging features usually are those of a large, multilocular cystic
      mass. There is, however, a spectrum of radiologic findings that overlaps with
      those of other entities including pancreatic pseudocyst, other primary epithelial
      and nonepithelial tumors of the pancreas, and metastases. In most cases,
      ultrasound and computed tomography are the mainstays for radiologic evaluation,
      with magnetic resonance imaging having a complementary role. All mucinous cystic
      neoplasms should be considered as mucinous cystadenocarcinomas of low-grade
      malignant potential. Complete surgical excision alone results in an excellent
      clinical outcome and disease-free survival, irrespective of histologic or
      radiologic parameters in over 90% of cases studied.

PMID- 9536489
TI  - The AAPM/RSNA physics tutorial for residents. X-ray interactions.
AB  - The diagnostic information in a radiograph or fluoroscopic image is largely the
      result of the quantity of x rays that are not removed from the incident x-ray
      beam. The information content of the image is delivered by the percentage of
      noninteracting photons that are successfully recorded. There are four major x-ray
      interactions: Rayleigh (coherent) scattering. Compton scattering, photoelectric
      absorption, and pair production. The degree of attenuation and the predominant
      mechanisms involved in the interactions are influenced by the x-ray energy and
      tissue composition. In the diagnostic energy range, photoelectric absorption and
      Compton scattering are the predominant modes of attenuation. One of the
      challenges in diagnostic imaging is to optimize image acquisition by controlling
      x-ray attenuation to obtain the appropriate contrast between the tissues while
      minimizing patient dose and scattered radiation in the image. Imaging techniques
      such as use of contrast material and dedicated mammography equipment exploit the
      differences in these types of x-ray interactions to improve the quality and
      diagnostic utility of the examination. Rayleigh scattering and pair production
      are presented but do not occur to any significant degree in diagnostic
      radiography.

PMID- 9536490
TI  - Introduction to wavelet-based compression of medical images.
AB  - Medical image compression can significantly enhance the performance of picture
      archiving and communication systems and may be considered an enabling technology
      for telemedicine. The wavelet transform is a powerful mathematical tool with many
      unique qualities that are useful for image compression and processing
      applications. Although wavelet concepts can be traced back to 1910, the
      mathematics of wavelets have only recently been formalized. By exploiting spatial
      and spectral information redundancy in images, wavelet-based methods offer
      significantly better results for compressing medical images than do compression
      algorithms based on Fourier methods, such as the discrete cosine transform used
      by the Joint Photographic Experts Group. Furthermore, wavelet-based compression
      does not suffer from blocking artifacts, and the restored image quality is
      generally superior at higher compression rates.

PMID- 9536491
TI  - Three-dimensional shaded-surface rendering of MR images of the breast: technique,
      applications, and impact on surgical management of breast disease.
AB  - Contrast material-enhanced magnetic resonance (MR) imaging is reported to be the
      most accurate modality for determining the extent of breast cancer before
      surgery. Three-dimensionally rendered MR images can be used as an adjunct in
      planning breast surgery. Semiautomated methods are used to isolate the breast
      tissue within high-resolution MR images and to render the skin with a shaded
      surface method. Cut-away views reveal lesions in the interior of the breast. Cut
      plane shaded-surface display provides the surgeon with information on the size,
      extent, and spatial relationships of a breast lesion in a simple, intuitive
      format. This technique can help the surgeon plan a breast biopsy, lumpectomy, or
      mastectomy that will maximize local control of breast cancer while minimizing
      cosmetic damage to the unaffected portions of the breast. In a review of 15
      clinical cases, cut-plane shaded-surface rendering aided surgical planning in 10
      cases.

PMID- 9536492
TI  - MRIW: parametric analysis software for contrast-enhanced dynamic MR imaging in
      cancer.
AB  - A software package called the Magnetic Resonance Imaging Workbench has been
      developed to characterize contrast agent uptake in vivo following T1-weighted
      magnetic resonance (MR) imaging with qualitative analysis of changes in signal
      intensity or quantitative analysis of changes in contrast agent concentration
      over time. Various descriptors may be calculated from the analysis of dynamic
      contrast agent-enhanced MR studies and visualized as false-color overlays, which
      allow the immediate display and interpretation of information taken from a series
      of images acquired over time. Qualitative descriptors include onset of
      enhancement, initial gradient, mean gradient, maximum enhancement, and washout.
      These parameters can be particularly useful in the investigation of multifocal or
      widespread disease. Quantitative descriptors include capillary permeability
      surface area product, extracellular volume, and T1 and may be used to monitor
      changes in the disease state and to assess the efficacy of treatment. In
      addition, they allow comparison of data obtained from different patients, from
      independent MR studies, or from studies performed with different modalities.
      Analysis of contrast enhancement during MR imaging in terms of such qualitative
      or quantitative parameters is a promising new method of data analysis in
      radiology.

PMID- 9536493
TI  - Hyperad: augmenting and visualizing free text radiology reports.
AB  - Hyperad is an automated computer system designed to extract key concepts from
      thoracic radiology reports and give physicians access to a large database
      containing the reports and key concepts. The concepts are extracted from textual
      documents with natural language processing techniques, then stored with the
      original documents in the database, which can be queried in terms of findings or
      associated attributes from an intuitive and easily accessible interface. The
      extracted concepts are represented both textually in a coded hypertext format and
      graphically on a coronal cross-sectional anatomy atlas, an idealized graphical
      model of human anatomy. To facilitate implementation, the communication protocols
      and standards of the World Wide Web (Web) were adopted. The reports and
      associated forms are encoded in standard hypertext markup language, which makes
      it possible to use hypermedia links to navigate the Hyperad database with any
      graphical Web browser. In the future, Hyperad may prove useful for other
      applications.

PMID- 9536494
TI  - MR imaging diagnosis of a urethral diverticulum.

PMID- 9536495
TI  - US case of the day. Solitary fibrous tumor of the pleura (SFTP).

PMID- 9536496
TI  - Neuroradiology case of the day. Vertebral arteriovenous fistula (AVF).

PMID- 9536497
TI  - General case of the day. Squamous cell carcinoma arising in a chronic draining
      sinus tract as a complication of chronic osteomyelitis.

PMID- 9536498
TI  - Pediatric case of the day. Wolman disease (primary familial xanthomatosis with
      involvement and clacification of the adrenal glands).

PMID- 9536499
TI  - Breast imaging case of the day. Dermatopathic lymphadenopathy.

PMID- 9536500
TI  - Risk indicators for recurrence among patients with coronary artery disease.
      Problems associated with their modification.
AB  - Various risk indicators associated with recurrence of a new ischemic event among
      patients with coronary artery disease are described and the impact of the
      implementation of a secondary preventive program on such risk indicators is
      evaluated. At Sahlgrenska Hospital in Goteborg 293 consecutive patients under the
      age of 70 years were followed for one to two years after an acute myocardial
      infarction (AMI), coronary artery bypass grafting (CABG), or percutaneous
      transluminal coronary angioplasty (PTCA). Enrollment and follow-up began after
      institution of a secondary preventive program among physicians and nurses at the
      hospital. A secondary preventive nurse was appointed and guidelines for risk
      factor modification were provided. The lipid guidelines were rather modest, with
      hyperlipidemia defined as cholesterol > 6.5 mmol/l or triglycerides > 3.0 mmol/l.
      The mean value for low density lipoprotein (LDL) cholesterol was 3.96 mmol/l at
      first screening and 3.94 mmol/l at second screening. Smoking was modestly
      reduced, from 36% at first screening to 26% at second screening (p < 0.01) It was
      found that 70% of all the patients had one or more of the following risk
      indicators at the first screening: s-cholesterol > 6.5 mmol/l (30%), s
      triglycerides > 3.0 mmol/l (19%), fasting blood glucose > 6.7 mmol/l (29%),
      systolic blood pressure > 160 mmHg (9%), diastolic blood pressure > 90 mmHg (8%)
      or smoking, compared with 67% one to two years later (p > 0.2). This is a clear
      demonstration of the difficulty in modifying risk indicators in patients, even
      with the aid of health-care professionals, in order to achieve risk-factor
      reduction in coronary artery disease.

PMID- 9536501
TI  - Parasympathetic neuropathy associated with left ventricular diastolic dysfunction
      in patients with insulin-dependent diabetes mellitus.
AB  - Patients with insulin-dependent diabetes mellitus (IDDM) may develop autonomic
      neuropathy (AN) and cardiac complications. The association between AN and cardiac
      dysfunction was assessed in 34 IDDM patients (age 40 years, diabetes duration 21
      years, 15 women) by echocardiography/Doppler and autonomic nerve function tests.
      The expiration/inspiration ratio (E/I) was used to assess parasympathetic damage,
      and the acceleration and brake indices for assessment of sympathetic impairment.
      AN was present in 21 patients. Patients with abnormal E/I (n = 11) had lower E/A
      ratios than patients without AN; early to atrial peak filling ratio (E/Amax) was
      median 1.1 (inter-quartile range 0.2) vs 1.4 (0.7), p = 0.022; early to atrial
      integral filling ratio (E/Aintegral) was 1.7 (0.3) vs 2.3 (1.2), p = 0.006.
      Patients with AN and normal E/I (sympathetic neuropathy, n = 10) and patients
      without AN had similar E/A ratios. E/Aintegral was also lower in patients with
      abnormal E/I compared with patients with AN and normal E/I; 1.7 (0.3) vs 2.2
      (0.7), p = 0.008. Systolic function and cardiac dimensions were generally
      unaffected and similar in the three groups. In conclusion, diastolic dysfunction
      and parasympathetic neuropathy are related in IDDM patients.

PMID- 9536502
TI  - Lung transplantation at the University of Lund 1990-1995. Analysis of the first
      39 consecutive patients.
AB  - Between 1990 and 1995 39 patients were lung transplanted at the University
      Hospital in Lund. This is a retrospective review of survival and lung function in
      these patients. There were 17 single-lung transplants (SLT), 21 double-lung
      transplants (DLT) and 1 heart-lung transplant (HLT). Seven patients died during
      the period, giving an overall survival of 82%. One-year survival according to
      Kaplan-Meier survival analysis was 87%, and 2-year survival was 83%. Vital
      capacity and forced expiratory volume in 1 s (FEV1) 1 year after transplantation
      were 91% and 100% of predicted, respectively, in the DLT group and 60% and 50% in
      the SLT group. Bronchiolitis obliterans syndrome (BOS) developed in 11 of the 35
      patients (31%) surviving more than 6 months, 2/21 in the DLT group and 8/13 in
      the SLT group and in the patient with HLT. The median time until detection of BOS
      was 11 months after the operation (range 6-18 months). Working capacity 1 year
      after transplantation was 60% of predicted in the DLT group and 47% of predicted
      in the SLT group. Ventilatory capacity was no longer function limiting. Lung
      transplantation today is a therapeutic option with a good medium-term survival
      and good functional results in selected patients with severe lung disease.

PMID- 9536503
TI  - Options for the management of poststernotomy mediastinitis.
AB  - The management of 27 consecutive deep sternotomy wound infections is reviewed. In
      22 cases the initial treatment was debridement, sternal refixation and dilute
      antibiotic irrigation via multiple irrigation-suction catheters. In the nine
      cases (41%) in which these measures failed, more extensive sternal and costal
      cartilage debridement and closure with a muscle flap were performed. Five cases
      were initially managed with major reconstructive surgery. For reconstruction, a
      bilateral pectoralis major myocutaneous flap was used alone in eight cases, while
      in six the flap was insufficient to obliterate the whole poststernectomy space,
      and was supplemented with rectus abdominis muscle. Early mediastinitis can be
      effectively treated with thorough wound debridement and mediastinal irrigation,
      but if there is a two-week delay from the initial sternotomy to manifestation of
      infection, radical debridement with muscle flap closure should be seriously
      considered.

PMID- 9536504
TI  - Treatment of infected median sternotomy wounds with a myocutaneous latissimus
      dorsi muscle flap.
AB  - Infected sternotomy wounds, particularly if accompanied by osteomyelitis,
      mediastinitis or pericarditis, are associated with significant morbidity,
      prolonged hospitalization and a mortality of up to 50%. Until the introduction of
      muscle flaps, the therapy of choice was debridement and open granulation or
      catheter irrigation. From 1994 to 1996, 9 patients with infected median
      sternotomy wounds were treated with a single-stage radical debridement and wound
      closure with a pedicled myocutaneous latissimus dorsi muscle flap (LDM). One
      patient received, in addition, a rectus abdominis muscle turnover flap. Healing
      was uneventful in all cases, with no respiratory complications or chest-wall
      instability. Shoulder strength was also unaffected. Functional and aesthetic
      outcome was good. The LDM provides a safe flap with little donor site morbidity.
      Compared to the most local muscle flaps, an intact IMA is not required. At the
      same time, length and cost of hospital stay are decreased.

PMID- 9536505
TI  - Amlodipine in patients with stable angina pectoris treated with beta-blockers.
      Double-blind comparison with placebo.
AB  - In order to assess additional anti-ischaemic effects of amlodipine (AML) on
      coronary artery disease (CAD) treated with beta-blockers, 32 patients with CAD,
      verified on angiograms, and stable angina were randomized to receive 5 mg/day of
      AML or placebo, increasing to 10 mg/day after 2 weeks. Baseline recording of 24-h
      ambulatory ECG and blood pressure, echocardiography and bicycle exercise test was
      repeated after treatment for 2 weeks and for 6 weeks. Reduction of ambulatory
      ischaemia was not significantly greater with AML than with placebo. In exercise
      tests the time to 0.1 mV ST segment depression and the total exercise time
      remained unaltered. Blood pressure was reduced by 10 mg AML. The total
      variability and the very low frequency component of heart rate were reduced after
      both doses. The clinical significance of the possible unfavourable change in
      autonomic modulation of the heart in CAD patients is not known.

PMID- 9536506
TI  - Conservative treatment of a paracardial abscess following post-infarct patch
      grafting.
AB  - A patient with previous patch grafts at the site of a ventricular aneurysm and
      over an ischaemic septal defect presented with an oval hypodense mediastinal mass
      consistent with a mediastinal abscess with blood cultures positive for
      Staphylococcus aureus. Surgical re-operation in this region was considered to be
      too risky and conservative treatment was pursued. Antibiotics were continued for
      a total of nearly 5 months of treatment. A computed tomographic scan prior to
      discharge indicated that the abscess was completely resolved.

PMID- 9536507
TI  - Ectopic parathyroid adenoma. Two cases treated with video-assisted thoracoscopic
      surgery.
AB  - In recurrent or persistent hyperparathyroidism, accurate location of the abnormal
      gland is essential before further surgery, but the variety of available imaging
      techniques suggests that no one procedure is universally reliable. We report two
      cases in which clear preoperative visualization of adenoma with double-phase
      99mTc-MIBI scintigraphy and exact high-resolution CT location permitted
      successful minimally invasive surgery.

PMID- 9536508
TI  - [Recruitment and selection of test subjects for scientific research in
      geriatrics: literature review and experiences of the Nijmegen NESTOR study].
AB  - The conduct of research in geriatric medicine differs from that in other medical
      specialties in a number of ways. In geriatric research it is almost impossible to
      study a large, homogeneous group of subjects, suffering solely from the problem
      to be studied. Moreover, measurements and questionnaires should be short, simple
      and not very troublesome. These differences are due to the heterogeneity of
      geriatric patients and the high prevalence of multimorbidity, often resulting in
      impaired physical, psychological and social performance. In this article a number
      of issues which are important for successful recruitment and selection of
      subjects for geriatric research are discussed. First, a review of relevant
      literature is given, and subsequently, experiences concerning recruitment and
      selection appreciated in the Nijmegen geriatric research programme' are
      described. This programme was part of the governmental Netherlands Programme for
      Research on Ageing (NESTOR). According to the literature the efficacy of
      recruitment may be improved by: personal contact between researcher and subject
      in view, introduction of the selection criteria already at the time of subjects'
      recruitment, a balance between research burden and profit, sufficient rewards for
      participation, both financially and non-financially, maximal effort in the
      subjects' transport, and also piloting of the recruitment procedure. In the
      NESTOR-studies the average number of subjects who were recruited and who
      completed the studies was low (23%), because a lot of the recruited subjects did
      not meet the selection criteria or considered participation as too troublesome.
      Subjects who agreed to participate showed high research compliance.

PMID- 9536509
TI  - [Perceived quality of life of elderly somatic nursing-home patients. Construction
      of a measuring instrument].
AB  - An instrument to assess perceived quality of life of physically frail elderly
      persons is needed in nursing home research. Four existing instruments (Pain,
      Somatic Autonomy, Life Satisfaction, Social Isolation) and two new scales
      (Perceived Safety, Perceived Autonomy) were tested for internal consistency,
      validity of the dimensional structure, discriminatory power, and feasibility. The
      scales were administered to 243 physically frail elderly nursing home patients.
      Three of the existing scales were shown to have sufficient internal consistency
      (KR-20 > .70), and the two new scales were moderately consistent (KR-20 > .50).
      The expected dimensions were confirmed in general by principal component analysis
      of the items. Significant group differences were detected by means of scale
      means. The mean administration time was 20 minutes. It is concluded that feasible
      instrument has been developed that can be applied in future research in nursing
      homes.

PMID- 9536510
TI  - [Decreased erythropoiesis and biochemical deviations in psychogeriatric
      patients].
AB  - Laboratory investigations were performed in group of 60 psychogeriatric patients
      on their admission into hospital, in order to elucidate the interdependence of
      erythropoiesis and the concentrations of albumin and several vitamins in blood or
      serum. The results of albumin concentration and ETK activity show that 47 out of
      60 the patients (= 78%) are in a poor nutritional condition. In 13 of these 47
      subjects (= 28%) deficiency with respect to vitamin B12 or folic acid is presumed
      from decreased serum concentrations. In 6 of the 47 patients in poor nutritional
      condition (= 13%) decreased reticulocyte concentrations are shown. Further
      evaluation of differences between the respective subgroups revealed significantly
      reduced ETK activity and lower reticulocyte concentrations in the group of
      delirium patients compared to the other patients groups and to the reference
      group.

PMID- 9536511
TI  - [Gerotranscendence as a life cycle perspective: an initial empirical approach
      among the elderly in The Netherlands].
AB  - Gerotranscendence has been defined as a shift in meta-perspective, from a
      materialistic and rationalistic perspective to a more cosmic and transcendent one
      that accompanies the process of aging. The present study describes scale
      characteristics of the Dutch translation of Tornstam's gerotranscendence scale,
      using data from a sample among adults aged 56-76 years (N = 556). Two subscales
      evolve from scale analysis, similar to those found by Tornstam: cosmic
      transcendence and egotranscendence. Scores on both subscales are higher for the
      older old, as well as for the unmarried; divorced or widowed respondents who
      suffer from physical impairments. Scale scores are also higher for respondents
      with depressive complaints. On the subscale cosmic transcendence Roman Catholics
      have higher scores than Protestants and non-church members. On the subscale ego
      transcendence well educated respondents and those with few social contacts have
      higher scores than persons with less education and those with many contacts. The
      strength of the associations is modest and the variance explained is small. The
      findings warrant further research into the question whether gerotranscendence
      adds to competence in later life.

PMID- 9536512
TI  - Effects of edifenphos and glyphosate on the immune response and protein
      biosynthesis of bolti fish (Tilapia nilotica).
AB  - The effects of 1/1000 field recommended concentration of the organophosphorus
      compounds; edifenphos and glyphosate on the immune response and protein contents
      were investigated after different time intervals. The cell mediated immune
      response assessed by proliferative response of splenocytes to mitogens;
      phytohemagglutinin (PHA) and concanavalin A (Con A) for T cell and
      lipopolysaccharide (LPS) for B cell decreased significantly in tems of the level
      of stimulation index in the treated fish and reached maximal depression after 4
      weeks. Humoral immunity assessed as splenic antibody plaque forming cells (PFC)
      measured after 5 days in vitro immunization to sheep erythrocytes (SRBC's) were
      suppressed in a concentration dependent pattern by the two compounds. The
      estimated ED50 for the PFC/10(6) cells of edifenphos and glyphosate were 1.48 x
      10(-2) uM and 1.65 x 10(-2) uM respectively. The data also showed that serum
      antibody titres in the treated fish were decreased in a time dependent manner.
      The total protein content of serum treated with the two pesticides was decreased
      after different time periods compared with control. The blood serum of treated
      and untreated Tilapia nilotica were analyzed electrophoretically for protein
      components and the percentage of proteins in each fraction was determined.

PMID- 9536513
TI  - Psychophysical evidence for a functional hierarchy of motion processing
      mechanisms.
AB  - Current models of motion perception typically describe mechanisms that operate
      locally to extract direction and speed information. To deal with the movement of
      self or objects with respect to the environment, higher-level receptive fields
      are presumably assembled from the outputs of such local analyzers. We find that
      the apparent speed of gratings viewed through four spatial apertures depends on
      the interaction of motion directions among the apertures, even when the motion
      within each aperture is identical except for direction. Specifically, local
      motion consistent with a global pattern of radial motion appears 32% faster than
      that consistent with translational or rotational motion. The enhancement of speed
      is not reflected in detection thresholds and persists in spite of instructions to
      fixate a single local aperture and ignore the global configuration. We also find
      that a two-dimensional pattern of motion is necessary to elicit the effect and
      that motion contrast alone does not produce the enhancement. These results
      implicate at least two serial stages of motion-information processing: a
      mechanism to code the local direction and speed of motion, followed by a global
      mechanism that integrates such signals to represent meaningful patterns of
      movement, depending on the configuration of the local motions.

PMID- 9536514
TI  - Nonlinear effects of localized absorption perturbations on the light distribution
      in a turbid medium.
AB  - A theoretical model of photon propagation in a scattering medium is presented,
      from which algebraic formulas for the detector-reading perturbations (delta R)
      produced by one or two localized perturbations in the macroscopic absorption
      cross section (delta mu a) are derived. Examination of these shows that when
      delta mu a is titrated from very small to large magnitudes in one voxel, the
      curve traced by the corresponding delta R values is a rectangular hyperbola.
      Furthermore, while delta Rinfinity identical to lim delta mu a-->infinity delta R
      is dependent on the location of the detector with respect to the source and the
      voxel, the ratio delta R/ delta Rinfinity is independent of the detector
      location. We also find that when delta mu a is varied in two voxels
      simultaneously, the quantity delta R (delta mu a,1 [symbol: see text] delta mu
      a,2) is a bilinear rational function of the delta mu aS. These results apply not
      only in the case of steady-state illumination and detection but to time-harmonic
      measurements as well. The validity of the theoretical formulas is demonstrated by
      applying them to the results of selected numerical diffusion computations.
      Potential applications of the derived expressions to image-reconstruction
      problems are discussed.

PMID- 9536515
TI  - Rapid modeling of diffuse reflectance of light in turbid slabs.
AB  - An efficient and accurate hybrid model of the Monte Carlo technique and the
      diffusion theory was developed to simulate the diffuse reflectance of light in a
      turbid slab due to an infinitely narrow light beam. The narrow beam was normally
      incident on the top surface of the slab. The hybrid model was accurate in
      modeling the diffuse reflectance near the light source, where the diffusion
      theory was most inaccurate. The hybrid model was much faster than a pure Monte
      Carlo method by a factor as great as several hundred, depending on the optical
      properties, the thickness of the slab, and the settings of the hybrid and the
      Monte Carlo computations. The computation speed of the hybrid model was
      insensitive to the optical properties of the medium, in contrast to the pure
      Monte Carlo technique. The diffusion theory was accurate in modeling both the
      diffuse reflectance far from the source and the diffuse transmittance. The hybrid
      model and the diffusion theory should be used in conjunction for efficient and
      accurate computation of diffuse reflectance and diffuse transmittance.

PMID- 9536516
TI  - Menadione-induced cell degeneration is related to lipid peroxidation in human
      cancer cells.
AB  - The role of lipid peroxidation, intracellular glutathione and Ca2+ concentration
      in menadione-mediated toxicity was investigated in human hepatoma cell lines, Hep
      G2 and Hep 3B, and in human leukemia cell lines, CCRF-CEM and MOLT-3. Incubation
      of these cells with 80 microM menadione at 37 degrees C resulted in depletion of
      intracellular glutathione, increased intracellular Ca2+, and increased lipid
      peroxidation, events leading to cell degeneration. The sensitivity of these cells
      to menadione, in order, was: Hep G2 cells > Hep 3B cells > CCRF-CEM cells and
      MOLT-3 cells. The extent of menadione-induced lipid peroxidation in different
      cell types followed the same order as did their susceptibility to menadione
      induced cell degeneration. The menadione-induced depletion in glutathione level
      was in the following sequence: Hep G2 cells > MOLT-3 and CCRF-CEM cells > Hep 3B
      cells. The extent of the menadione-induced increase in the intracellular Ca2+
      concentration was: Hep G2 cells > Molt-3 cells > CCRF-CEM cells and Hep 3B cells.
      Pre-treatment of Hep G2 cells with 20 mM deferoxamine mesylate, an iron chelator,
      reduced both the menadione-induced cell degeneration and lipid peroxidation;
      however, it did not prevent the menadione-induced increase in intracellular Ca2+
      nor the depletion of glutathione. These data suggest that menadione-induced cell
      degeneration is directly linked to lipid peroxidation, and that it is less
      related to the rise in intracellular Ca2+ and the depletion in glutathione
      content. Dicumarol (an inhibitor of DT diaphorase) enhanced the capacity of
      menadione to induce Hep 3B cell degeneration from 71.3% to 86.2% after 120 min of
      menadione treatment at 37 degrees C, but did not have this effect in Hep G2, CCRF
      CEM or MOLT-3 cells. The activities of DT diaphorase were 52.4, 39.6, 1.5 and 1.8
      nmol cytochrome c reduced/min/mg protein in Hep G2, Hep 3B, CCRF-CEM and MOLT-3
      cells, respectively. The activity of DT diaphorase was much higher in Hep G2
      cells than in the other cells. It seems that DT diaphorase may not, as suggested
      by others, protect against cell degeneration by quinones, such as menadione.

PMID- 9536517
TI  - Effects of insulin on protein phosphorylation and protein kinase C activity in
      human malignant gliomas.
AB  - Modulation of protein phosphorylation activities by insulin was investigated in
      glioma and normal glial cells. Insulin suppressed the in vitro protein
      phosphorylation of glioma cells in a dose-dependent manner while it stimulated
      that of meningiomas, neurilemmomas and glial cells. Although gliomas and glial
      cells contained different species of tyrosyl phosphoproteins before treatment,
      they expressed similar kinds of tyrosyl phosphoproteins in response to insulin.
      Insulin increased the activities of casein kinase II and total protein kinase C
      (PKC) in glioma and normal glial cells. The membrane-bound PKC activity in U373
      MG cells was elevated by insulin. The PKC isozymes, including subtypes alpha,
      beta, delta, epsilon and gamma, were detected in gliomas, but few were found in
      glial cells. Insulin down regulated the cytosolic PKC-gamma and the membrane
      bound PKC-epsilon proteins in gliomas. These results indicate that an altered
      insulin signaling pathway exists in human gliomas, which might involve
      differential regulation of PKC isozymes.

PMID- 9536518
TI  - Human alpha-L-iduronidase (IDUA) gene: correlation of polymorphic DNA haplotype
      and IDUA activity in Chinese population.
AB  - The correlation of polymorphic DNA haplotype of the alpha-L-iduronidase (IDUA)
      gene and IDUA activity in Chinese subjects was investigated. Genomic DNA
      extracted from 85 randomly sampled normal individuals was used to amplify
      fragments containing the polymorphic change site A8, Q33H (exon 1), R105Q (exon
      3), A361T (exon 8), or V454I (exon 9). The PCR amplified products were analyzed
      by means of restriction fragment length polymorphism (RFLP) or allele specific
      oligonucleotide (ASO) hybridization. Leukocytes were isolated from the above 85
      samples, and their IDUA activities were determined. A wide range of IDUA activity
      (50-300 nmol/h/mg cell protein) with an average of 156 nmol/h/mg cell protein was
      observed. When the allele frequency was compared between individuals with IDUA
      activity below 90% or above 110% of the average, a bias toward the common allele
      "1" of Q33H (Gln33) was detected in individuals with higher IDUA activity.
      Conversely, the polymorphic allele "2" of R105Q (Gln105), A361T (Thr361), and
      V454I (Ile454) was found in the higher IDUA activity group. Linkage
      disequilibrium analysis of the haplotype data revealed strong nonrandom
      association among the polymorphic alleles of R105Q, A361T, and V454I. Of the
      haplotypes constructed by Q33H, R105Q, A361T, and V454I, a positive correlation
      between haplotype 1,2,2,2 (Gln33, Gln105, Thr361, Ile454) and IDUA activity was
      observed. The IDUA activity was found to increase with Gln105, Thr361, or Ile454
      polymorphic changes by mutagenesis and expression of IDUA cDNA in COS-7 cells. By
      combining the positive effect of Gln105, Thr361, and Ile454 in one cDNA
      construct, it may be possible to produce a high activity IDUA protein for MPS I
      enzyme replacement therapy.

PMID- 9536519
TI  - Combined effects of dexamethasone and aminoguanidine on rats with endotoxemia.
AB  - The effects of a combination of dexamethasone (DEX, an inhibitor of inducible
      nitric oxide synthase (iNOS) synthesis) and aminoguanidine (AG, an inhibitor of
      iNOS activity) on the anesthetized rat treated with endotoxin
      (lipopolysaccharide, LPS) were examined. In addition, we investigated whether a
      complete inhibition of nitric oxide (NO) formation caused by LPS prevents the
      hypotension, restores the vascular hyporeactivity to normal and improves the
      survival rate. The combination of DEX (3 mg/kg at 30 min prior to LPS) plus AG
      (15 mg/kg at 2 h after LPS) inhibited the overproduction of nitrate (an indicator
      of NO) and prevented the development of delayed hypotension, but further enhanced
      tachycardia in rats treated with LPS for 6 h. In addition, the vascular
      hyporeactivity to norepinephrine (NE) was, however, only partially restored in
      endotoxemic rats treated with DEX plus AG. During the experimental period, the
      survival rate of LPS-rats treated with DEX plus AG was also improved when
      compared to that of rats treated with LPS only. The beneficial effects of the
      combined therapy with DEX plus AG on rats with endotoxemia, suggesting that (i)
      combined treatment of animals with DEX plus AG may reduce some of the detrimental
      effects of LPS and (ii) NO only partially contributes to the vascular
      hyporeactivity in endotoxic shock.

PMID- 9536520
TI  - Beneficial effects of tetramethylpyrazine, an active constituent of Chinese
      herbs, on rats with endotoxemia.
AB  - Tetramethylpyrazine, an inhibitor of phosphodiesterase, has been widely used for
      treatment of cardiovascular diseases in China. Here, we investigate the effects
      of tetramethylpyrazine on hypotension, vascular hyporeactivity to norepinephrine
      (NE), release of tumor necrosis factor-alpha (TNF alpha) and nitric oxide (NO) in
      a rat model of circulatory shock induced by bacterial endotoxin (E. coli
      lipopolysaccharide, LPS). Male Wistar-Kyoto rats were anesthetized and
      instrumented for the measurement of mean arterial pressure (MAP) and heart rate
      (HR). Injection of LPS (10 mg/kg, i.v.) resulted in a fall in MAP and an increase
      of HR. In contrast, animals pretreated with tetramethylpyrazine (10
      micrograms/kg, i.p. at 30 min prior to LPS) maintained a significantly higher
      MAP, but tachycardia was further enhanced at 60 min and 120 min when compared to
      rats given only LPS (LPS-rats). The pressor effect of NE (1 microgram/kg, i.v.)
      was also significantly reduced after treatment of rats with LPS. Similarly, the
      thoracic aorta obtained from rats after in vivo studies showed a significant
      reduction in the contractile responses elicited by NE (1 microM). Pretreatment of
      LPS-rats with tetramethylpyrazine partially, but significantly, prevented this
      LPS-induced hyporeactivity to NE in vivo and ex vivo. The injection of LPS
      resulted in a significant increase in the plasma TNF alpha level at 60 min,
      whereas the effect of LPS on the plasma nitrate (an indicator of NO formation)
      level increased in a time-dependent manner. This increment of both TNF alpha and
      nitrate levels induced by LPS was significantly reduced in LPS-rats pretreated
      with tetramethylpyrazine. The early hypotension caused by LPS was slightly, but
      significantly, prevented by pretreatment with tetramethylpyrazine, suggesting
      that tetramethylpyrazine affects the endothelial constitutive NOS (eNOS). This
      was examined by the effect of tetramethylpyrazine on acetylcholine (ACh, 1
      microM)-induced relaxation in rats treated with tetramethylpyrazine for 4 h.
      However, tetramethylpyrazine had no significant effects on the ACh-induced
      relaxation, indicating that tetramethylpyrazine does not affect the activity of
      eNOS. Thus, tetramethylpyrazine attenuates the early hypotension and the delayed
      circulatory failure caused by endotoxin in the rat. These effects may be due to
      inhibition of the release of circulation factors and TNF alpha, which usually
      reveal synergism upon the induction of iNOS.

PMID- 9536521
TI  - The role of automated peritoneal dialysis (APD) in an integrated dialysis
      programme.
AB  - While there is no doubt that renal transplantation would be the preferred option
      for all patients suffering from end stage renal disease, this is sadly an
      unrealistic aim for many patients in the UK. There is a shortage of donor organs
      and, with the increasing percentage of elderly patients on dialysis, under 50% of
      all dialysis patients are on the national transplant waiting list. Of the 12,000
      or so patients on dialysis in the UK, approximately half receive haemodialysis
      and half peritoneal dialysis. In the last few years, there has been a resurgence
      of interest in automated peritoneal dialysis and just under 20% of the peritoneal
      dialysis population currently receive this mode of therapy. The advantages of
      automated peritoneal dialysis include the capacity for an increased dialysis
      prescription, increased freedom and quality of life and a decreased risk of
      peritonitis and intra peritoneal pressure related problems. These advantages may
      offset the increased cost of automated peritoneal dialysis and long-term patient
      morbidity and mortality may be diminished by its provision in an integrated
      dialysis programme.

PMID- 9536522
TI  - Artificial heart transplants.
AB  - The use of a mechanical device to support a failing heart is one of the greatest
      challenges in cardiothoracic practice. Many different approaches are being
      considered, but they share the use of many advanced engineering principles. Power
      supplies and the interface between artificial surfaces and the blood remain areas
      of difficulty. The accent is moving from console driven devices with drive lines
      which must cross the body wall to reach the pump, towards smaller control packs,
      with inductive coupling to fully contained pumps. More attention is focused on
      the use of axial pumps lying within the lumena of the great vessels and the
      ventricles. Despite the wideheld belief that mechanical pumps must confer
      survival advantage to the recipients, there has been no prospective study
      demonstrating any advantage over medical management of the failing heart.
      Economic considerations must be taken into account if the technology is to be
      available to everyone with heart failure.

PMID- 9536523
TI  - Novel strategies for liver support in acute liver failure.
AB  - At present, the treatment of a patient in acute liver failure is based upon
      scrupulous intensive care. In those patients whose condition deteriorates,
      emergency liver transplantation must be considered. There would be great benefit
      if it were possible to provide treatment which would stabilise the condition of a
      patient in acute liver failure. Thus, there is great incentive to develop a means
      of artificial liver support. Over many years, a considerable array of therapeutic
      strategies has been investigated. These can be considered in four main
      categories: plasma exchange, haemofiltration, extra-corporeal liver assist
      devices (ELAD), extra-corporeal liver perfusion (ECLP). Finally, the role of
      xenotransplantation is considered.

PMID- 9536524
TI  - Bioartificial liver support: developments in hepatocyte culture and bioreactor
      design.
AB  - Bioartificial liver devices aim to support patients with acute liver failure
      (ALF) until orthotopic liver transplantation (OLT) or spontaneous recovery due to
      hepatic regeneration can occur. However, initial clinical experiences with two
      devices have indicated that functional efficacy in this setting may be less than
      in the experimental situation. Several fundamental issues remain unresolved,
      including the cell mass required to provide meaningful support and which of those
      hepatocyte components and bioreactor designs so far proposed is best able to do
      this. In particular, further studies of the efficacy of devices incorporating
      human hepatocyte lines transformed by either cultural conditions or genetic
      engineering and those based on multi-channel or flat bed bioreactor designs in
      which hepatocytes are co-cultured with non-parenchymal cells are awaited.
      Controlled trials on a multicentre basis in well-defined patient groups and with
      standardised outcome measures will be required to properly evaluate the clinical
      value of these devices. A better understanding of factors promoting recovery and
      regeneration of the native liver and to what extent these can be provided by
      extracorporeal devices will be essential to the further development of effective
      bioartificial liver support systems.

PMID- 9536525
TI  - Extra-corporeal membrane oxygenation for paediatric respiratory failure.
AB  - Extracorporeal membrane oxygenation (ECMO) uses modified cardiopulmonary bypass
      technology to provide prolonged respiratory or cardiorespiratory support for
      patients of all ages who have failed conventional intensive care management. The
      use of ECMO for neonatal respiratory failure is now evidence-based following the
      publication of the randomised UK Collaborative Trial. ECMO use in children
      remains more controversial, but overall survival of 71% is possible in a group of
      moribund patients whose mean PaO2/FIO2 ratio of 61 mmHg accurately predicts death
      in studies of conventional ventilation. Common diagnoses for children requiring
      ECMO support are pneumonia and the acute respiratory distress syndrome (ARDS).

PMID- 9536526
TI  - Neuronal cell transplantation for Parkinson's and Huntington's diseases.
AB  - The brain constitutes a privileged transplantation site. Under appropriate
      conditions neuronal tissues can survive transplantation into the damaged brain,
      integrate with the host, and alleviate functional impairments associated with
      neurological disease. The experimental techniques have been developed to the
      point of clinical application with demonstrable benefit in Parkinson's disease,
      and similar applications in Huntington's disease appear to be imminent.
      Nevertheless, present techniques require use of embryonic/fetal tissues which
      will limit the availability of donors for the foreseeable future. There is an
      active search for alternative sources of tissue that are equally effective but
      more readily available, including engineered cells, expanded stem/precursor
      cells, and xenografts.

PMID- 9536527
TI  - Encapsulated islet cells: the role of direct and indirect presentation and the
      relevance to xenotransplantation and autoimmune recurrence.
AB  - Immuno-isolation of islet tissue for the purpose of curing diabetes without
      immunosuppression is an attractive concept that has been extensively investigated
      over the last 20 years. Rather than give a detailed review of the past and
      present history of the immuno-isolation or encapsulation approach for islet
      transplantation, this paper will examine the concepts behind encapsulation,
      concentrating on the immune mechanisms involved.

PMID- 9536528
TI  - Recent developments in transplantation of the small intestine.
AB  - The widespread application of intestinal transplantation depends upon achieving a
      success rate sufficiently high to warrant treating patients by transplantation
      rather than parenteral nutrition. This is analogous to the situation in renal
      transplantation (where the alternative is dialysis) and pancreatic
      transplantation (insulin treatment) and contrasts with the situation in liver and
      heart transplantation where there is no effective alternative therapy. The main
      barrier to success at this level is immunological; progress will depend on
      improved prevention, diagnosis and treatment of rejection. Although developments
      are expected of new and more potent immunosuppressive drugs, it is possible that
      acceptable long-term results will require a more fundamental manipulation of the
      immune response in order to achieve at least partial tolerance of the graft.

PMID- 9536529
TI  - Tissue banking programmes in Europe.
AB  - In Europe, organ centres such as Bio Implant Services (BIS) in cooperation with
      Eurotransplant, play an intermediary role from donation of tissue and organs to
      allocation and transplantation. They take responsibility for donor medical/safety
      screening and organize procurement. Tissue banks are autonomous and are
      responsible for tissue processing and preservation. Allocation of scarce tissues
      is performed according to rules set by committees of renowned experts in the
      field. Most frequently donated types of tissues are corneas, heart valves, bone
      and soft tissue and skin. In this article, optimal serological screening of the
      donor, and the banking of these tissues in Europe is reviewed in relation to
      clinical need and volume of transplantable tissues available, number of banks and
      their organisational level, methods of explantation, processing and preservation,
      quality standards and new developments.

PMID- 9536530
TI  - Organ shortages: maximising the donor potential.
AB  - Of all the problems foreseen in the pioneering days of organ transplantation, a
      shortage of donor organs, was not even remotely considered as a barrier to
      progress. Such has been the success of transplantation over the last two decades,
      organ shortage is now considered the major limitation. This chapter will
      concentrate on efforts to increase the donor potential. The development of Organ
      Exchange Organizations is briefly described with special emphasis on their role
      in organ allocation systems to avoid wastage of this precious resource,
      procurement transplant coordinators, the organization of organ procurement and
      the consent process. We look briefly at the influence of the media and end with
      some considerations on how to maximise the current supply of organs for
      transplantation.

PMID- 9536531
TI  - The retrieval of thoracic organs: donor assessment and management.
AB  - The optimal management of the multi-organ donor is critical to the successful
      outcome of transplantation. It is a complex challenge demanding careful attention
      to detail, and requiring a shift in emphasis, since the pathophysiological
      processes have far reaching effects which many clinicians do not see on a day-to
      day basis. The optimal management of haemodynamic and respiratory status is
      essential in order to maximise the yield of suitable thoracic donor organs, yet
      this process will also improve the condition of other organs at the time of
      procurement and thus enable prompt recovery of function following hepatic and
      renal transplantation. The process commences when a potential donor is
      identified, and is only complete after successful transplantation of all possible
      organs. In order to achieve this end, a dedicated, multi-disciplinary team is
      necessary, consisting not only of medical staff, but also support workers who
      organise logistics, and who play their own part in vital areas, such as transport
      of the donor team and organs. The co-ordinator's role is pivotal in bringing
      together, in harmony, teams from different centres. It is important to remember
      that the effort of every person involved in the management and procurement of
      donor organs is primarily directed towards maximisation of the donor pool, and
      that our main responsibility is to the recipients on our waiting lists.

PMID- 9536532
TI  - The non heart-beating donor.
AB  - Given the shortage of donor kidneys for transplantation, we have focused on the
      use of non heart-beating (NHB) donor kidneys since 1982. The major drawback for
      the use of NHB donor kidneys is the inherent possibility of severe ischaemic
      damage leading to primary non function. Thus viability assessment of
      ischaemically damaged kidneys is crucial, and, therefore, a machine perfusion
      programme was reinstituted in 1993. Machine perfusion (MP) enables viability
      assessment through analysis of perfusion characteristics and measurement of
      enzyme release into the perfusate. Of the last 100 consecutive MP NHB donor
      kidneys, 71 kidneys were transplanted and 29 kidneys were discarded. Nine kidneys
      started functioning immediately, 51 kidneys showed delayed function and 11
      kidneys never functioned. When analysing in retrospect different parameters for
      viability assessment, only alpha-GST, an enzyme specific for damage of proximal
      tubular cells within the kidney, could discriminate between functioning and non
      functioning kidneys. With this promising viability assessment, the large NHB
      donor potential and the good transplant results, we recommend the use of these
      donors.

PMID- 9536533
TI  - Unrelated living donor kidney transplants.
AB  - Due to the shortage of cadaver donor kidneys in the US, an increasing effort has
      been made to supplement the donor supply with transplants from unrelated living
      donors (URLD). In the present communication, we wish to update the URLD results
      from the United Network for Organ Sharing (UNOS) Kidney Transplant Registry.
      Since we last published the results, the number of such transplants has more than
      doubled.

PMID- 9536535
TI  - Intestinal transplantation: living related.
AB  - The use of live donors in intestinal transplantation could potentially both
      reduce the severity of rejection responses against this highly immunogenic organ
      by better tissue matching and also reduce cold ischaemia times. These two
      advantages over cadaveric grafts could preserve mucosal integrity and reduce the
      risk of systemic sepsis from bacterial translocation. The disadvantages of live
      donation are the inherent risk to the donor and the compromise of using a shorter
      graft. Although only a handful of such cases have been performed, the success
      rate has been high and this is a therapeutic modality which should be explored
      further.

PMID- 9536534
TI  - Liver splitting and living donor techniques.
AB  - Split liver transplantation (SLT) and living related transplantation (LRT) have
      been developed following advancements in liver surgery. In experienced hands they
      can yield results comparable to full organ liver transplantation. They are today
      a reality which has to be implemented and used more widely. LRT is the best
      procedure available and should be the method of choice despite the high success
      of SLT. Any method safely enlarging the pool of donors has to be utilized,
      especially in view of the possible future application for adults. The procedures
      should be initially performed and tested in centres specialized in liver
      transplantation and liver surgery, with the aim of making the techniques more
      widely available in the future. High ethical standards are required to perform
      LRT. In the short term, SLT and LRT are the methods more apt to increase the
      organ pool and thus decrease pre-transplant mortality both in children and
      adults.

PMID- 9536536
TI  - Living related donor pancreas and pancreas-kidney transplantation.
AB  - Our experience with living related donor (LRD) pancreas transplants shows that
      they can be performed with low morbidity and mortality for both donors and
      recipients. The recipient survival rate is 90% at both 1 and 5 years post
      transplant. Our overall pancreas graft survival rate is comparable to that for
      cadaver transplants; if only technically successful cases are included, the graft
      survival rate is significantly better for LRD (versus cadaver) transplants.
      Advantages for LRD recipients include fewer rejection episodes, less
      immunosuppression, lower incidence of graft loss from rejection, and elimination
      of waiting time. Donor mortality in our series was 0%, and the incidence of
      surgical complications about 10-15%. LRD pancreas transplants are an attractive
      option for endocrine replacement therapy in certain diabetic patients. Optimal
      candidates are: (i) patients who are highly sensitized and have a low probability
      of receiving a cadaver graft; (ii) patients who should avoid high-dose
      immunosuppression; (iii) patients with nondiabetic identical twins; and (iv)
      uremic patients who want one operation with no waiting in order to remain or
      become dialysis free as well as insulin-independent. These transplants can be
      performed safely in all recipient categories--pancreas transplant alone, pancreas
      after kidney or simultaneous pancreas-kidney transplant. In all groups, LRD
      transplants should be done only when the donor, the recipient, and the entire
      family understands the advantages and disadvantages of LRD versus cadaver
      transplants.

PMID- 9536537
TI  - Lung: living related transplantation.
AB  - As with other paired and lobed solid organs, surgical techniques have now evolved
      to permit safe live donation. Almost all the published experience comes from one
      centre, with cystic fibrosis recipients receiving right and left lower lobes,
      typically one from each parent. Donor morbidity has been acceptable, with no
      known deaths. Early survival, perhaps because patients are only transplanted in
      extremis, has been less good than can be achieved in cadaver transplantation.
      Early and late rejection remain at least as common as after conventional
      transplants, but is nearly always asynchronous, affecting one lung at a time.
      There remain significant ethical difficulties, and the approach has yet to prove
      itself.

PMID- 9536538
TI  - Xenogeneic transplantation.
AB  - Hyperacute rejection, the previously insurmountable obstacle to pig-to-human
      xenografts, has been overcome. There is reason to hope that concerted research
      will overcome the remaining obstacles. Pigs will be produced expressing other
      regulators of complement activation molecules in addition to decay accelerating
      factor. Modification of antigenic structure of cells could also be achieved.
      There is now some hope that large scale clinical xenotransplantation could become
      a reality.

PMID- 9536539
TI  - The ethics of organ donation.
AB  - As organ transplantation is physically possible within a tension between common
      biological properties and individual immunities, so it is ethically possible
      within a tension between individual personality in full integrity and the human
      community of which each member, social by nature, is an organic part. Ethical
      donation is by consent, explicit or presumed, spontaneously offered or procured
      by request. Altruism or commercial dealing is now a live issue in organ
      procurement, whether cadaveric or by live donation, related or unrelated.
      Attention is given to children in transplantation, and to new developments with
      fetal organs, neural tissue, bone marrow and xenografts. Given all that medical
      science and skill can now offer, patients are still free to decline.

PMID- 9536540
TI  - Investigation of the mechanism of action of 2% fusidic acid lotion in the
      treatment of acne vulgaris.
AB  - We describe the results of a single-centre, double-blind, vehicle-controlled,
      parallel group study on the quantitative effects of 2% fusidic acid lotion
      (Fucidin lotion) in facial acne vulgaris. The trial was completed by 52 patients
      aged 15-25 years with mild to moderate acne who had been randomized to either
      Fucidin Lotion (n = 25) or its base (n = 27). Primary outcome measures included
      colony counts of Propionibacterium acnes and micrococcaceae and measurements of
      skin surface lipid free fatty acids and sebum excretion rate. Clinical assessment
      was based on the acne grade, count of inflamed and non-inflamed lesions and
      evidence of a primary irritant dermatitis. There was a variable but gradual
      reduction in lesion counts with the maximum improvement at 12 weeks for inflamed
      lesions, where the reduction was 19.9% for fusidic acid and 24.7% for the
      placebo. The non-inflamed lesions decreased by 10.8% in the fusidic acid group
      and increased by 15.9% in the placebo group; this difference was not
      statistically significant. Although the fusidic acid reduced the micrococcaceae
      count by 1 log cycle, inferring adequate compliance, there was no reduction in
      the counts of P. acnes, surface free fatty acids or sebum excretion rate. This
      study has failed to explain the mechanism of action of topical fusidic acid.

PMID- 9536541
TI  - Topical lithium succinate ointment (Efalith) in the treatment of AIDS-related
      seborrhoeic dermatitis.
AB  - A randomised, double-blind, placebo-controlled trial with lithium succinate
      ointment was conducted in patients with AIDS-associated facial seborrhoeic
      dermatitis. Twice daily applications of the ointment brought about a rapid (2.5
      days) and highly significant (P = 0.007) improvement in the severity of the
      condition. Lithium succinate ointment is well tolerated and can be a useful
      treatment for seborrhoeic dermatitis in this group of patients.

PMID- 9536542
TI  - Epidermolysis bullosa acquisita in childhood--a case mimicking chronic bullous
      dermatosis of childhood.
AB  - Epidermolysis bullosa acquisita (EBA) is rarely reported in childhood, but we now
      describe a 6-year-old Korean girl with the condition. She presented with multiple
      tense bullae annularly distributed on the perioral, periorbital and genital
      areas, and was successfully treated with dapsone. The clinical and histological
      features were similar to those of chronic bullous dermatosis of childhood. We
      review seven previously reported childhood EBA cases and contrast their features
      with those of adult EBA. We suggest that some childhood EBA is different from the
      adult form and shares features with chronic bullous dermatosis of childhood.

PMID- 9536544
TI  - Lack of expression of the recombination activating genes RAG-1 and RAG-2 in
      cutaneous T-cell lymphoma: pathogenic implications.
AB  - Analyses of the karyotype and genome of cutaneous T-cell lymphoma (CTCL) cells
      have shown that they contain chromosome breaks and translocations. The sequence
      analyses of such DNA breakpoints found in various kinds of leukaemias have
      suggested that some of the observed translocations have been caused by
      illegitimate V(D)J (v = Variability; D = diversity; J = joining) recombination.
      To study whether illegitimate V(D)J recombination is responsible for the
      continuously increasing number of DNA breaks in CTCL, we used reverse
      transcriptase polymerase chain reaction (RT-PCR) to analyse three CTCL cell lines
      and biopsies from 14 CTCL patients for the expression of the RAG-1 and RAG-2
      genes which are essential for V(D)J recombination. We found no RAG gene
      expression in any of the 17 samples analysed, indicating that illegitimate V(D)J
      recombination may not be the reason for the increased number of chromosomal
      aberrations and translocations in CTCL cells.

PMID- 9536543
TI  - Characterization of circulating immune complexes in leprosy patients and their
      correlation with specific antibodies against Mycobacterium leprae.
AB  - Circulating immune complex (CIC) levels and their antibody and antigenic
      composition were evaluated in patients with leprosy as well as in any individuals
      living with them; they were precipitated with 3.5% polyethylene glycol (PEG) and,
      after affinity chromatography isolation and purification, analysed by sodium
      dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblot
      with monoclonal antibodies (Mabs). The presence of CICs was demonstrated
      throughout the clinical and immunopathological leprosy spectrum at levels related
      to bacterial load, and in leprosy patients they showed a positive correlation
      with specific anti-PGL and anti-65 kDa antibodies. The isolation and analysis,
      however, failed to identify any Mycobacterium leprae antigenic components;
      although two specific antibodies anti-PGL-1 and anti-65 kDa were identified as
      possible CIC constituents and may be potentially useful in the follow-up of
      leprosy patients, especially to check bacterial load evolution, PGL-1 being an
      authentic antigen of this mycobacterium. Also, the involvement of 65 kDa in CICs,
      being homologous with the human heat shock protein (HSP) 60 kDa family, suggests
      an autoimmune mechanism in leprosy pathogenesis. Furthermore, those results
      support the inclusion of CIC antibody reactivity studies to enhance the
      sensitivity of serology.

PMID- 9536545
TI  - Reticular erythematous mucinosis syndrome. Report of a case with positive
      immunofluorescence.
AB  - We report a case with the clinical and histological features of the reticular
      erythematous mucinosis syndrome (REM), in which there was moderate, continuous,
      fine, granular, IgM deposition along the basal layer. Similar direct
      immunofluorescence results have been reported in only two previous cases.

PMID- 9536546
TI  - Congenital superficial angiomyxoma.
AB  - Superficial angiomyxomas are rare, benign, dermal and subcutaneous tumours. We
      describe a 12-year-old girl who presented with a nodular swelling in the midline
      of her scalp that had been present since birth. Histological examination revealed
      an ill-defined myxoid lesion within the dermis, comprising spindle cells, blood
      vessels and occasional multi-nucleate giant cells. Immunohistochemical staining
      was negative for S-100, cytokeratin and smooth muscle actin, but focally positive
      for CD34. Our patient is unusual in that the angiomyxoma was present at birth,
      which has not previously been described. The importance of screening patients
      with cutaneous myxomas for cardiac lesions is discussed.

PMID- 9536547
TI  - Giant Becker's naevus with ipsilateral areolar hypoplasia and limb asymmetry.
AB  - We report a case of giant Becker's naevus, ipsilateral areolar hypoplasia and
      limb asymmetry in a 48-year-old male. This is the first case in which Becker's
      naevus with areolar hypoplasia has been reported to be associated with other
      defects.

PMID- 9536548
TI  - Petrified ears.

PMID- 9536549
TI  - Topical glyceryl trinitrate: a possible treatment for cutaneous leishmaniasis.
AB  - The treatment of cutaneous leishmaniasis (CL) is difficult in both the old and
      new worlds. However, nitric oxide (NO) is involved in host cell mediated immune
      responses against intracellular parasites such as Leishmania major, and both in
      vitro and in vivo immunological studies indicate that Leishmania parasite killing
      by macrophages is mediated by this substance. Glyceryl trinitrate (GTN) is an
      exogenous NO donor; we have successfully treated a young man with cutaneous
      leishmaniasis with topical GTN. We believe this to be the first reported use of
      GTN in the treatment of human CL.

PMID- 9536550
TI  - Localized unilateral hyperhidrosis secondary to an eccrine naevus.
AB  - We describe a patient with intermittent unilateral hyperhidrosis localized to the
      left hand only. Histology confirmed the presence of an eccrine naevus.

PMID- 9536551
TI  - Segmental neurofibromatosis: an uncommon variant of neurofibromatosis.

PMID- 9536552
TI  - Yellow nail syndrome following Guillain-Barre syndrome.

PMID- 9536554
TI  - Sarcoidosis presenting as nodules in both tattoos and scars.

PMID- 9536553
TI  - Toxic epidermal necrolysis and cyclosporin.

PMID- 9536555
TI  - Treatment of molluscum contagiosum with the pulsed tuneable dye laser.

PMID- 9536556
TI  - Eosinophil cationic protein in eosinophilic pustular folliculitis: an
      immunohistochemical investigation.

PMID- 9536557
TI  - HRT and SERMS--increasing benefit, reducing risk?

PMID- 9536558
TI  - Postmenopausal HRT--a role for a safe antioestrogen.

PMID- 9536559
TI  - Postmenopausal HRT--a role for a safe antioestrogen.

PMID- 9536560
TI  - Women's awareness of, and attitudes towards, hormone replacement therapy: ethnic
      differences and effects of age and education.
AB  - To investigate ethnic differences and the effect of age and education on
      awareness and attitudes of women towards hormone replacement therapy (HRT), we
      conducted a questionnaire survey of 180 women attending a gynaecology clinic, of
      whom 152 (84.4%) responded. Seventy-one of the women had heard of HRT. Awareness
      of HRT was higher in the 50-59 year age group and in women with higher education,
      but lower in Indo-Asian women than in white and black/Afro-Caribbean women.
      Friends, relatives and the media were important sources of information (apart
      from the doctor), especially among the younger age groups. The women themselves
      ranked their overall understanding of HRT as 'low'; 78% felt they did not know
      enough about the subject. A distorted perception of benefits/risks associated
      with HRT was also noted--cardiovascular protection was not appreciated, whereas
      there was an excessive fear of breast cancer. Twenty-eight per cent of the
      menopausal, postmenopausal and hysterectomised women surveyed were current HRT
      users. We conclude that factors such as ethnicity, age and educational level have
      an impact on women's awareness of and attitudes towards HRT. Some confusion about
      the real benefits/risks still exists, which probably accounts for low acceptance
      of this treatment, and suggests that clinicians prescribing HRT need to be aware
      of these problems.

PMID- 9536561
TI  - Osteopetrosis in children.
AB  - Over a 10-year period, 28 Arab children with autosomal recessive osteopetrosis
      were seen in two hospitals in Riyadh, Saudi Arabia. Eighteen (64%) had
      osteopetrosis associated with metabolic acidosis probably due to a renal tubular
      defect; nine (32%) had a malignant infantile form of osteopetrosis and one had a
      mild form with delayed onset. Parental consanguinity was 56% and 40% among
      patients with and without acidosis respectively. Somatic and psychomotor
      retardation and recurrent bone fractures were common in both groups. Dental
      caries, cerebral calcification and optic atrophy were more frequent in patients
      with acidosis, while anaemia, hepatosplenomegaly and deafness were more common in
      patients without acidosis. To guarantee optimal rehabilitation, children with
      this progressive disease require an early multiteam approach.

PMID- 9536562
TI  - Drug allergy: fact or fiction?
AB  - From our clinical practice, it was apparent that patients often reported drug
      allergies without a substantiating history. A prospective study over six months
      was undertaken to examine the reporting of drug allergies by hospital patients.
      Based on the history, allergic reactions were triaged into one of three
      categories: high probability of an allergic reaction, low probability of an
      allergic reaction, and uncertain, where the history was incomplete or unclear. Of
      1519 patients interviewed, 133 (9%) reported prior drug allergies. The most
      commonly implicated agents were penicillin (74%), septrin (6%), aspirin (6%),
      cefuroxime (2%) and trimethoprim (2%); 61% of reactions were deemed to be high
      probability, with the remainder either low (29%) or uncertain (10%) probability.
      It was apparent that patients often considered drug allergy to be synonymous with
      adverse reaction. Preventing patients from being labelled as drug allergic, thus
      being denied therapy with first-line agents, requires patient education and
      vigilance by doctors in their history-taking.

PMID- 9536563
TI  - A study of chest infections in HIV seropositive patients in Kuala Lumpur.
AB  - A retrospective study of 144 adults with HIV infection was conducted to
      investigate the prevalence of upper and lower respiratory tract infections (URTIs
      and LRTIs). The patients were divided into two groups: those with acquired HIV
      through intravenous drug abuse (IVDA), and those who had acquired HIV through
      'other' risk behaviours. LRTIs were more prevalent than URTIs overall, and LRTIs
      were significantly more common (p < 0.001) in IVDAs than in the other-risk group.
      Tuberculosis (40%) and bacterial pneumonias (33%) comprised the majority of LRTIs
      among IVDAs, while Pneumocystis carinii pneumonia (40%) was the commonest LRTI in
      the other-risk group. Analysis of CD4 T-lymphocyte counts indicated that HIV
      seropositive IVDAs are at greater risk of developing chest infections at higher
      CD4 counts than other-risk patients. The IVDAs were also found to have a much
      higher rate of co-infection with hepatitis C and B, which may be a factor
      accelerating the progression from HIV infection to AIDS. The mean time averaged
      for the two groups from known seroconversion to development of respiratory tract
      infection is only 1.37 years, which suggests HIV-infected patients are presenting
      late for treatment in Malaysia.

PMID- 9536564
TI  - Promoting effective communication in neonatal intensive care units by audiotaping
      doctor-parent conversations.
AB  - Parents of newborn babies receiving intensive care may find it difficult to
      understand, remember and accept information. We evaluated how practical and
      useful it is to give parents a tape recording of their initial conversation with
      the neonatologist. They seem to benefit from being able to listen repeatedly to
      such recordings. Parents and nurses have similar scores of usefulness of the
      method but their score is significantly higher than that of the neonatologists.
      This method could be useful in other clinical situations.

PMID- 9536565
TI  - Sumatriptan suppositories for the acute treatment of migraine. S2B351 Study
      Group.
AB  - A randomised, double-blind, parallel-group, placebo-controlled trial was
      undertaken to assess the efficacy and tolerability of the sumatriptan suppository
      in 184 patients with acute migraine. Patients used a sumatriptan suppository
      (12.5 mg or 25 mg) or placebo at home for the treatment of a moderate or severe
      migraine attack and those who experienced headache recurrence within 24 hours of
      dosing had the option to repeat the dose. By 2 hours post-dose, 68% of patients
      in the sumatriptan 25 mg group and 47% of patients in the sumatriptan 12.5 mg
      group compared with 25% of placebo patients achieved headache relief. Relief
      rates 2 hours post-dose for nausea, vomiting, photophobia and phonophobia were
      similar to those reported 2 hours post-dose for headache. Post hoc review of the
      recurrence data showed that administration of a second suppository was effective
      in alleviating recurrent headache in over 80% of the sumatriptan-treated patients
      experiencing recurrence. No serious or unusual adverse events were reported, and
      the pattern and incidence of adverse events did not vary as a function of dose.
      These data demonstrate that the sumatriptan suppository is a well-tolerated,
      effective treatment for the acute treatment of migraine pain and its associated
      symptoms.

PMID- 9536566
TI  - Management of thyrotoxicosis in pregnancy.
AB  - Between April 1985 and June 1995, 20 patients being treated for thyrotoxicosis
      became pregnant. These patients are reviewed. Control of thyrotoxicosis early in
      pregnancy using minimal doses of propylthiouracil or carbimazole, followed by
      subtotal thyroidectomy in the middle trimester, is safe for both mother and
      fetus.

PMID- 9536567
TI  - Clinical applications of photodynamic therapy.
AB  - Photodynamic therapy is a modality for the treatment of malignant disease in
      which a photosensitive drug is selectively absorbed or retained by malignant
      tissues, after intravenous injection and is then photoactivated by light of an
      appropriate wavelength, often produced by a laser. Over the past two decades, the
      combination of haematoporphyrin derivative (HPD) and then its active component
      dihaematoprophyrin ether (DHE), now marketed as Photofrin, plus red light at 630
      nm have been used in clinical practice for the treatment of a range of tumours;
      some very promising results have been obtained. Several countries have approved
      this drug/light combination for clinical use for a number of tumours. Some second
      generation photosensitising agents with appropriate light sources, and with
      perceived advantages over Photofrin, are under investigation, and it is to be
      hoped that major improvements in drug/light combinations will enable photodynamic
      therapy to achieve its full potential in the not-too-distant future.

PMID- 9536568
TI  - Paediatric xanthogranulomatous pyelonephritis.
AB  - Xanthogranulomatous pyelonephritis (XGP) is a well recognised but rare type of
      chronic pyelonephritis classically occurring in middle-aged women. It is
      increasingly being recognised in children in whom it can be mistaken for Wilms'
      tumour. Awareness of the possibility of this condition occurring in children may
      allow early recognition and possible treatment. Two cases of XGP in children are
      described and the literature reviewed.

PMID- 9536569
TI  - Intravenous conscious sedation with midazolam in paediatric patients.
AB  - Intravenous midazolam has been widely used in paediatric patients for conscious
      sedation in procedures such as endoscopy, oesophageal manometry, biopsy, bone
      marrow aspiration and lumbar puncture. Its advantages include quick onset and
      short duration of action, and haemodynamic stability which may be associated with
      improved patient acceptance. The pharmacokinetic profile of midazolam compares
      favourably with that of diazepam, permitting more controlled sedation with a
      quicker recovery time. Midazolam has been associated with shorter recovery room
      stays and less vomiting in children who undergo outpatient surgery. The safety
      and tolerability profile of midazolam in paediatric patients is comparable or
      superior to that observed in adults. Patients who are haemodynamically unstable,
      as well as pre-term and term infants are at greater risk of hypotension while
      receiving sedation. Thus, the availability of i.v. midazolam for use in children
      provides an important additional option for providing i.v. conscious sedation.

PMID- 9536570
TI  - Report from the 70th annual meeting of the American Heart Association, Orlando,
      Florida, 10-14 November 1997.

PMID- 9536571
TI  - 'Cardiac claudication': ischaemic heart disease presenting as intermittent
      claudication.

PMID- 9536572
TI  - Tuberculous tenosynovitis: a rare manifestation of a common disease.
AB  - Two cases of tuberculous tenosynovitis of the hand are presented. The clinical
      features were those of a gradually enlarging swelling and mild pain over several
      months. Diagnosis was not initially suspected in either patient, reflecting
      decreased awareness of this uncommon condition. Both patients had concomitant
      active pulmonary tuberculosis which was quiescent in the second patient. Combined
      surgical debridement and antituberculous drugs led to a successful outcome. The
      condition is discussed and pertinent literature is reviewed.

PMID- 9536573
TI  - Rectal administration of demeclocycline in a patient with the syndrome of
      inappropriate ADH secretion.

PMID- 9536574
TI  - Retroperitoneal perforation of duodenal ulcer presenting as scrotal sepsis.
AB  - Retroperitoneal extravasation is an extremely uncommon complication of duodenal
      ulcer perforation. The preoperative diagnosis is difficult and may even by missed
      at operation. There were 25 cases reported in the literature. Only one patient
      was correctly diagnosed preoperatively and only seven patients survived. We
      describe the first case of retroperitoneal extravasation from perforated duodenal
      ulcer presenting as scrotal sepsis.

PMID- 9536575
TI  - TSH secreting pituitary adenoma: a rare cause of thyrotoxicosis.
AB  - Thyroid-stimulating hormone (TSH) secreting pituitary adenoma is a rare but
      important cause of thyrotoxicosis. It poses a challenge for both diagnosis and
      management. We report the case of a young Chinese man presenting with
      thyrotoxicosis, complicated by congestive heart failure, secondary to a TSH
      secreting pituitary adenoma. The case illustrates the importance of prompt
      diagnosis and allows discussion of both medical and surgical management,
      including the use of a long-acting somatostatin analogue.

PMID- 9536576
TI  - Stable angina: two important trials--RITA-2 and ACIP( Asymptomatic Cardiac
      Ischaemia Pilot)

PMID- 9536577
TI  - Surgery for lung cancer in the elderly.

PMID- 9536579
TI  - Anticoagulant control in the first three months after mechanical heart valve
      replacement.
AB  - To establish the precision of anticoagulant control in the first three months
      after mechanical heart valve replacement, 53 patients from a consecutive series
      of 91 were telephoned and asked to read out their anticoagulation record. The
      levels of international normalised ratio (INR) were analysed by Rosendaal's
      method. Twenty-nine per cent of patient days were spent with an INR in the
      recommended range of 3.0-4.5. Warfarin dosage was increased at a median INR of
      2.1 (interquartile range 1.7-2.3), unchanged at 2.7 (interquartile range 2.3-3.1)
      and decreased at 4.3 (interquartile range 3.6-5.1). Anticoagulant control is poor
      in the first three months after mechanical heart valve replacement. Data on the
      INR at which warfarin dosage is changed suggest either that recommended
      guidelines are not being followed or a reluctance to increase the dosage in
      patients receiving inadequate anticoagulation.

PMID- 9536578
TI  - Surgery for lung cancer: age alone is not a contraindication.
AB  - A retrospective analysis of the clinical features, operative procedures,
      postoperative complications and subsequent survival of 70 (50 male) elderly
      patients undergoing surgery for lung cancer compared with 74 (53 male) younger
      patients treated at the same hospital during the same period was performed, to
      determine if elderly people with lung cancer are less likely to benefit from
      and/or tolerate surgery. The elderly group had to wait longer for operation (p =
      0.001) and were more likely to have pre-existing disease (p = 0.019). In
      contrast, they had fewer recognised postoperative complications (p = 0.032) and
      there was no difference between the two groups in perioperative mortality and
      subsequent survival. Surgical treatment of localised lung cancer represents the
      best chance for cure and this study suggests that age should not be a
      consideration in the decision to operate or not. The patient's general state of
      health should be assessed and management decisions based on individual status
      rather than on age.

PMID- 9536580
TI  - Comparison between reagent strips used for detection of urinary tract infection
      in the elderly.
AB  - A comparison was made between the accuracy of Ames and Boehringer reagent strips
      for detecting urinary tract infections in 100 elderly patients (50 acutely ill
      patients admitted to hospital and 50 attending the day hospital). The results for
      urinary nitrite, blood and protein for both strips were documented. Nitrite
      provided the highest sensitivities and specificities. In the acute hospital
      patients, the sensitivities were 83% for the Ames and Boehringer strips
      respectively, while for the day hospital patients the sensitivities were 90% for
      both strips. Specificities were 100% for both strips in each group of patients.
      There was thus little difference between the accuracy of the Ames and Boehringer
      reagent strips in detecting urinary tract infection.

PMID- 9536581
TI  - An audit of patients admitted for home intravenous therapy directly from the
      emergency department.
AB  - The Hospital in the Home Unit (HHU) provides home intravenous therapy to acute
      inpatients. The aim of this audit was to assess the practice of accepting
      patients for home intravenous therapy directly from the emergency department by
      describing the frequency and type of clinical conditions managed, and recording
      the outcome and adverse events of such admissions. Consecutive patient admissions
      to the HHU directly from the emergency department over a 15-month period were
      included. The policy of accepting patients for home intravenous therapy from the
      emergency department will continue. Care with diagnosis and HHU assessment is
      required. Complications should be expected, and a reliable on-call service is
      essential.

PMID- 9536582
TI  - A study of autonomic cardiovascular reflexes in elderly patients with pneumonia.
AB  - People recovering from pneumonia are often weak for no apparent reason. Clinical
      features such as postural hypotension, arrhythmia and syndrome of inappropriate
      ADH have, in other circumstances, been attributed to impaired autonomic function.
      The aim of this study was to see whether elderly patients with pneumonia had
      impaired autonomic cardiovascular reflexes and, if so, how long this persisted.
      We compared healthy elderly controls, elderly controls with trauma (fractured
      femoral neck) and elderly patients with pneumonia. Thirty-eight subjects were
      studied in a series of cardiovascular autonomic function tests. Results suggest
      that elderly people have a high prevalence of impaired cardiovascular autonomic
      reflexes in the immediate post-pneumonic phase, and that this improves
      significantly after six weeks, with a further improvement by six months. Elderly
      patients recovering from pneumonia are predisposed to the adverse effects of
      drugs and other factors which can further impair autonomic cardiovascular
      reflexes.

PMID- 9536583
TI  - Inhaler use in chronic obstructive pulmonary disease.
AB  - Inhaler technique is a common problem, particularly in the elderly. We have
      assessed the ability to use seven common inhaler devices in 20 patients with
      chronic obstructive pulmonary disease (COPD). Techniques were taught in a
      standard fashion in random order and assessed immediately and one hour later by
      two observers. Fourteen patients had a fault that would result in no drug
      delivery at some time during the study, and such a fault occurred at some point
      for each inhaler device. These faults were most common with the diskhaler.
      Accuhaler, autohaler and turbohaler scored highest and diskhaler lowest. Overall
      scores declined by one hour after instruction. Patients ranked the metered dose
      inhaler and accuhaler highest for ease of use and preference. These results show
      that it is useful to have a small range of devices for patients with COPD and
      that it is important to review inhaler technique regularly.

PMID- 9536584
TI  - Why do imminent victims of a cardiac event feel so tired?
AB  - A state of vital exhaustion, characterised by unusual tiredness and lack of
      energy, increased irritability and feelings of demoralisation, has been found to
      be one of the precursors of myocardial infarction and other cardiac events. These
      feelings probably reflect decreased activity of the hypothalamic-pituitary
      adrenal axis. Treatment of the conditions leading to this state of vital
      exhaustion might decrease the risk of a cardiac event.

PMID- 9536585
TI  - REM sleep behaviour disorder: an overview.
AB  - REM sleep behaviour disorder (RSBD) is a recently described parasomnia
      characterised by a history of excessive nocturnal motor activity and absence of
      muscle atonia during REM sleep. Only limited literature is available on this
      condition. The exact prevalence is unclear, but recent studies suggest it might
      not be an uncommon condition. The elderly are more often affected and there is a
      male preponderance. While transient RSBD can be seen after taking certain drugs
      or during drug withdrawal, the chronic type is usually idiopathic or associated
      with an underlying degenerative neurological condition. It can result in
      considerable distress and/or serious injury to the patients or their bed
      partners. Differential diagnoses include sleep-walking, night terrors,
      nightmares, nocturnal seizures, obstructive sleep apnoea, post-traumatic stress
      disorder, dissociative states and nocturnal confusional states. The dramatic
      response to clonazepam highlights the importance of recognition and appropriate
      treatment of this sleep disorder.

PMID- 9536586
TI  - Chronobiology and chronopathophysiology of nocturnal asthma.
AB  - Asthma is increasing in prevalence and severity worldwide despite effective
      treatment and innovative research developments. Chronobiology is the study of
      biological rhythms and their mechanisms. Asthma is one of many diseases that
      exemplifies a circadian pattern in intensity, frequency of attacks and mortality.
      As many as 90% of asthmatics experience nocturnal symptoms severe enough to
      awaken them from sleep. Increased airway narrowing at night is thought to occur
      as a result of circadian variation in neurohormones and intensification of airway
      inflammation. Furthermore, vagal tone, neurogenic inflammation and airway
      hyperresponsiveness are increased at night. Many cells contribute to the
      nocturnal inflammatory process in the asthmatic airways, including mast cells,
      eosinophils, neutrophils and lymphocytes. These cells are capable of secreting
      innumerable inflammatory mediators, such as histamine, cytokines, leukotrienes,
      prostaglandins, neutral endopeptidase and superoxides, which are potent
      bronchoconstrictors and secretogogues. They also cause increased vascular
      permeability and airway oedema. All these chronobiological events promote
      nocturnal worsening of asthma and increased nocturnal deaths. Understanding the
      mechanisms of nocturnal asthma will help us learn more about asthma, and how to
      implement appropriate chronotherapeutic interventions.

PMID- 9536588
TI  - Coarctation of the aorta: an unusual cause of hypertension in a 73-year-old
      woman.

PMID- 9536587
TI  - Report from the XVII Congress of the European Society of Cardiology, Stockholm,
      Sweden, August 1997.

PMID- 9536589
TI  - Emphysematous pyelonephritis responding to medical therapy.
AB  - We describe two type 2 diabetic patients with unilateral emphysematous
      pyelonephritis who responded to medical treatment alone. Escherichia coli was
      isolated in both patients. The presence of gas was confirmed early by ultrasound
      and CT scan of abdomen. Following treatment, good functional recovery was
      demonstrable in the affected kidneys by isotope renogram. We stress the need for
      early diagnosis of this condition and aggressive treatment with broad spectrum
      antibiotics.

PMID- 9536590
TI  - Primary thyroid carcinoma and thyrotoxicosis.
AB  - A 60-year-old man noticed rapid enlargement of a long-standing thyroid goitre,
      with dysphagia and difficulty in breathing. Thyrotoxicosis was diagnosed. Chest X
      ray revealed multiple pulmonary metastases. He underwent near-total
      thyroidectomy. The histopathology revealed an undifferentiated thyroid carcinoma
      with some areas of papillary carcinoma and its follicular variant. Postoperative
      131I total body scan showed residual thyroid tissue in the neck and one
      functioning metastasis in the right rib, posteriorly. The patient's condition
      deteriorated rapidly and he died from pneumonia. The autopsy showed widespread
      metastases of undifferentiated thyroid carcinoma. Only the right rib contained
      the follicular variant of papillary carcinoma.

PMID- 9536591
TI  - Medial orbital wall blowout fracture with medial rectus muscle entrapment.

PMID- 9536592
TI  - Acromegaly in a woman presenting with diabetic ketoacidosis and insulin
      resistance.
AB  - A 22-year-old Chinese woman presented with typical features of diabetic
      ketoacidosis. There was a family history of diabetes but she was not obese.
      Plasma glucose and bicarbonate levels were 27.0 mmol/l and 5 mmol/l,
      respectively. Significant insulin resistance was noticed: she needed up to 15
      units of insulin per hour. She required up to 120 units daily for her diabetic
      control even after her acidosis had subsided. She was then noticed to have the
      clinical features of acromegaly. The diagnosis was confirmed, and a cranial CT
      scan confirmed the presence of a pituitary macroadenoma. She underwent uneventful
      trans-sphenoidal resection of the tumour and her insulin requirement gradually
      lessened. Acromegaly should be considered in the differential diagnosis of
      unexplained insulin resistance.

PMID- 9536593
TI  - Spontaneous cervical epidural haematoma.
AB  - Spontaneous spinal epidural haematoma can occur in the elderly and is a
      reversible cause of neurological deficit if treated promptly. The diagnosis can
      be made from a careful history and a simple neurological examination, but it can
      be confused with myocardial infarct, musculoskeletal pain, vasculitis and acute
      dissection of an aortic aneurysm. For a favourable outcome, early decompressive
      laminectomy and evacuation of the haematoma are necessary. We report an unusual
      case of acute quadriplegia in which prompt diagnosis and early intervention led
      to almost complete functional recovery with minimal disability.

PMID- 9536594
TI  - Koch's or Crohn's--or something else?

PMID- 9536595
TI  - New principles of biometry 'not being observed'.

PMID- 9536596
TI  - Clinical audit--KISS it better.

PMID- 9536597
TI  - Tonsillitis: its causes, management and possible complications.

PMID- 9536598
TI  - Emergency tracheostomy in general practice.
AB  - We set out to review the need for general practitioners (GPs) to be skilled at
      forming an emergency alternative airway by assessing mortality figures for acute
      airways obstruction. We also solicited the views of 100 GPs on the theory and
      practice of emergency tracheostomy and assessed whether they considered they were
      equipped to carry out such a procedure in the community. The results suggest a
      significant number of deaths of otherwise young and healthy individuals could be
      avoided by training community practitioners in emergency alternative airway
      formation. The results showed a marked lack of confidence in the practice of
      emergency airway formation and few GPs felt able to carry out the procedure. They
      indicated an overwhelming interest in receiving further education on the subject.
      We recommend that formal training programmes in the techniques of emergency
      airway formation should be available for community GPs.

PMID- 9536599
TI  - The significance of urinary N-acetyl-beta-D-glucosaminidase for predicting early
      stage diabetic nephropathy.
AB  - We studied urinary N-acetyl-beta-D-glucosaminidase (NAG) in the early stage of
      diabetic nephropathy in 27 non-insulin-dependent diabetes mellitus (NIDDM)
      patients with a microalbumin level below 20 mg on 24-hour urine sample.
      Microalbumin and NAG excretion were measured in 24-hour urine samples collected
      on three separate occasions within seven days of admission. Creatinine clearance
      was determined simultaneously. There was a significant negative correlation
      between the creatinine clearance and 24-hour urinary NAG (r = -0.38, p < 0.05).
      Elevation of urinary NAG may indicate decreased renal function during early stage
      NIDDM nephropathy.

PMID- 9536601
TI  - Colorectal adenoma in patients with a history of breast cancer: a prospective
      study in Taiwan.
AB  - The increased incidence of colorectal cancer in women with a history of breast
      cancer is well established. However, the relationship between the prevalence of
      adenomatous polyps and breast cancer is still controversial. We conducted a
      prospective study of the incidence of colorectal polyps in patients with a
      history of breast cancer in Taiwan. Eighty-nine patients (86 women and 3 men)
      received colonoscopy to test for precancerous lesions. Mean age was 49.4 +/- 10.4
      years. Twelve polyps (9 adenomatous, 2 hyperplastic, 1 inflammatory) (13.5%) and
      one cancer (1.1%) were found. The mean age of patients with and without
      colorectal neoplasia was 56.3 +/- 9.4 and 48.2 +/- 10.2 years respectively, (p <
      0.005); 10 out of 13 patients (77%) with colorectal neoplasia were over 50 (p <
      0.1). Compared with a study of Chinese people in Hong Kong, our population had a
      lower incidence of colorectal adenomatous polyps, but breast cancer patients have
      a greater risk of developing colorectal cancer than the general population in
      Taiwan.

PMID- 9536602
TI  - The impact of direct access endoscopy, Helicobacter pylori near patient testing
      and acid suppressants on the management of dyspepsia in general practice.
AB  - Direct access endoscopy services, Helicobacter pylori infection and more
      effective acid suppression therapy have influenced the management of dyspepsia in
      the past decade. Three hundred and ten GPs in south London were surveyed via
      postal questionnaire to determine the impact of these factors on the management
      of dyspepsia in general practice. Ninety-one per cent of GPs prescribed simple
      antacids as initial treatment for simple dyspepsia and referred only if symptoms
      did not improve. When acid suppressants were used, 41% used H2 antagonists
      compared with 11% for proton pump inhibitors (p = 0.0001). Risk factors for
      underlying malignancy were the most frequent reason for hospital referral at
      first consultation. Long outpatient waiting times result in about 90% of GPs
      choosing direct access endoscopy as the route of referral for all patients with
      dyspepsia, while only 36% would refer patients with sinister symptoms to direct
      access endoscopy if waiting times were similar to that of outpatients. H. pylori
      near patient testing did not seem to influence the management of dyspepsia in
      general practice.

PMID- 9536600
TI  - Lithium follow-up in general practice.
AB  - Lithium salts have been used in medicine for over a century and are a widely
      accepted treatment. Clinical practice in the London borough of Barnet led us to
      suspect that agreed guidelines were not being followed. We checked them against
      published guidelines and followed up their implementation. A list of patients on
      lithium was obtained from the local biochemistry laboratory and a representative
      sample extracted. We looked at the frequency of laboratory testing and compared
      it with the guidelines. We found that the standards for lithium therapy follow-up
      were not being met and that while we awaited the outcome of our consultant
      psychiatrists' committee deliberations, the recommendations were not being
      implemented. A lithium register or clinic needs to be established in the area,
      and there is also a need for more reliable and effective implementation of
      clinical audit recommendations.

PMID- 9536603
TI  - Mechanisms of hypophosphataemia in alcoholic patients.
AB  - The aim of our study was to determine the possible pathophysiological mechanisms
      of hypophosphataemia in a group of 127 patients admitted to hospital for alcohol
      related causes. Blood and fresh urine specimens were taken to determine acid-base
      and electrolyte parameters. Thirty-seven patients (29.1%) had hypophosphataemia
      (serum phosphorus < 0.77 mmol/l) with a range of serum phosphorus of 0.32-0.74
      mmol/l. In 17 hypophosphataemic patients inappropriate phosphaturia (FEPO4 > 20%,
      TmPO4/GFR < 0.80 mmol/l) was evident, possibly due to hypomagnesaemia, metabolic
      acidosis, metabolic alkalosis, or a proximal tubular defect in phosphate
      transport. The causes of hypophosphataemia in the remaining 20 patients were
      alcohol withdrawal syndrome, respiratory alkalosis and diarrhoea. Patients with
      hypophosphataemia were more often found to have hypomagnesaemia and respiratory
      alkalosis than normophosphataemia patients. In conclusion, hypophosphataemia is
      frequently observed in alcoholic patients due to various pathophysiological
      mechanisms, such as inappropriate phosphaturia, increased phosphorus entry into
      cells and increased gastrointestinal loss of phosphate.

PMID- 9536604
TI  - The medical management of stroke.
AB  - The management of stroke, so long a 'Cinderella' condition, is changing rapidly
      as new developments appear for acute treatment, rehabilitation and secondary
      prevention. Most patients with acute stroke now need rapid assessment at hospital
      following the onset of symptoms. Those needing admission should be managed on an
      acute stroke unit for stabilisation, CT scanning and other investigation, and
      diagnosis, and then referred, as appropriate, to a specialist stroke
      rehabilitation unit. Aspirin is now the recognised treatment for acute ischaemic
      stroke (once primary intracerebral haemorrhage has been excluded), and can be
      continued for secondary prevention. Attention should be paid to risk factors to
      prevent recurrence, especially treatment of hypertension, atrial fibrillation,
      and severe ipsilateral carotid stenosis. Patients with mild cerebrovascular
      disease should be managed in a specialist stroke/TIA clinic. Stroke is no longer
      an untreatable or unpreventable condition, and it is vital that hospitals design
      appropriate systems to manage patients in an interdisciplinary environment.

PMID- 9536605
TI  - The management of thyroglossal duct cysts.
AB  - Thirty patients undergoing surgery for a preoperative diagnosis of thyroglossal
      duct cyst have been reviewed. All patients were seen in a hospital service for
      patients of 16 years and over. Sistrunk's procedure is the operation of choice
      but when histological examination of a thyroglossal duct cyst reveals a papillary
      carcinoma, total thyroidectomy should be considered.

PMID- 9536606
TI  - The use of mobile telephones in a district general hospital.
AB  - Advances in technology have led to the increased availability of mobile
      telephones, but their use in an NHS hospital has not previously been reported.
      Junior doctors require easy access to a telephone, but ward telephones are
      frequently busy and not readily accessible when urgently needed. A one-year
      retrospective study was carried out on the use of mobile telephones in a small
      district general hospital.

PMID- 9536607
TI  - Does smoking influence the eradication of Helicobacter pylori and duodenal ulcer
      healing with different regimens?
AB  - To determine the effect of smoking on Helicobacter pylori eradication and ulcer
      healing, we investigated 232 patients with H. pylori-positive duodenal ulcer.
      Patients were given one of seven different treatment protocols and divided into
      three groups according to smoking habits. Group 1 (n = 128) consisted of non
      smokers, group 2 (n = 65) of mild smokers (5-20 cigarettes/day) and group 3 (n =
      39) of heavy smokers (> 20/day). The eradication of H. pylori and ulcer healing
      rate was controlled eight weeks later after ceasing the therapy. The overall
      eradication rate was 66% in all patients and 68%, 66%, 59% in each group,
      respectively. The eradication rates showed no statistical difference between
      groups. Complete ulcer healing was achieved in 84% of all patients and ulcer
      healing rate between groups did not show any significance (85%, 83% and 82%
      respectively). These results suggest that smoking status does not influence the
      eradication of H. pylori and duodenal ulcer healing rates at eight weeks in
      patients on different treatment schedules.

PMID- 9536608
TI  - A case of schistosomal appendicitis.
AB  - Acute appendicitis is a great masquerader in surgical practice; its diverse
      clinical presentation can sometimes lead to delay in diagnosis. Nonetheless, the
      underlying aetiology of acute appendicitis may not be apparent if the appendix is
      not sent for histological examination.

PMID- 9536609
TI  - Gastrointestinal autonomic nerve tumour presenting as small bowel volvulus: a
      rare disease with a rare presentation.
AB  - A 78-year-old Chinese woman presented with recurrent postprandial abdominal pain.
      Computerised tomography revealed a small bowel tumour causing volvulus of a
      segment of the small bowel. Laparotomy confirmed an extraluminal ileal tumour
      with partial volvulus of the involved small bowel segment. Small bowel resection
      was done. Histological and ultrastructural studies confirmed a gastrointestinal
      autonomic nerve tumour. We review the medical literature on this rare tumour.

PMID- 9536610
TI  - Subacute cerebellitis in Lyme disease.
AB  - Cerebellitis is not a recognised manifestation of Lyme disease. We describe a
      patient with clinical features of subacute cerebellitis, cerebrospinal fluid
      (CSF) monocytic pleocytosis, positive CSF Borrelia burgdorferi antibodies,
      negative brain magnetic resonance imaging and a benign course after treatment
      with ceftriaxone. Possible earlier cases are discussed. Lyme disease should be
      considered in all cases of subacute cerebellitis.

PMID- 9536611
TI  - Diphallus with urethral duplication: a rare case.
AB  - We report on a case of glandular diphallus with incomplete urethral duplication
      associated with rotation anomaly in the right kidney, and a bifid pelvis and an
      ectopic ureteral orifice in the left kidney. The bladder was single with good
      sphincter control. At operation, the hipoplasic glans was resected and the
      urethra which opened into this glans anastomosed alongside the other urethra.
      Diphallus and incomplete urethral duplication are discussed.

PMID- 9536612
TI  - Blunt laryngeal trauma: an unusual case.
AB  - Local external evidence of neck trauma--bruising, subcutaneous emphysema, cuts,
      abrasions and so on--signs of upper airway obstruction, dysphonia and dysphagia
      are the hallmarks of laryngotracheal lesions. Such lesions tend to occur after
      motor vehicle accidents and usually require surgery. We describe a case of blunt
      laryngeal trauma, resulting from an unusual mechanism, which healed
      spontaneously.

PMID- 9536613
TI  - Gastrostomy-related pancreatitis in a child: a fatal case.
AB  - A case of acute pancreatitis following gastrostomy feeding tube insertion is
      presented. This is a rare and fatal complication, which has not been described
      before. The role of the gastrostomy catheter and total enteral nutrition in the
      causation of acute pancreatitis is discussed. Pathologists and clinicians should
      be aware of this disastrous and potentially avoidable condition.

PMID- 9536614
TI  - Scrotal suppuration following appendicitis.
AB  - Inguinoscrotal sepsis following intraperitoneal infection is a recognised but
      infrequent complication. Incidence of this condition seems to have decreased
      because of the routine use of broad spectrum antibiotics. It is believed that a
      persistent communication between the peritoneal cavity and scrotum, in the form
      of a patent tunic vaginalis, is needed for this complication. There may or may
      not be an associated hernia. Intrascrotal sepsis can lead to testicular loss from
      vascular thrombosis. The treatment of choice is early operative drainage.

PMID- 9536615
TI  - Koch's or Crohn's: the debate continues.

PMID- 9536616
TI  - "For a healthy London": the Socialist Medical Association and the London County
      Council in the 1930s.

PMID- 9536617
TI  - Sir William Wilde's medico-legal observations.

PMID- 9536618
TI  - Sunlight therapy and solar architecture.

PMID- 9536619
TI  - A database for John Locke's medical notebooks and medical reading.

PMID- 9536620
TI  - Medical gymnastics and the Cyriax collection.

PMID- 9536621
TI  - A danger to the public? Disposing of pauper lunatics in late-Victorian and
      Edwardian England: Plympton St Mary Union and the Devon County Asylum, 1867-1914.

PMID- 9536622
TI  - Unsuitable cases: the debate over outpatient admissions, the medical profession
      and late-Victorian London Hospitals.

PMID- 9536623
TI  - Goitre, cretinism and iodine in South Asia: historical perspectives on a
      continuing scourge.

PMID- 9536624
TI  - The great experiment: the admission of women students to St Mary's Hospital
      Medical School, 1916-1925.

PMID- 9536625
TI  - The papers of Walter Pagel in the Contemporary Medical Archives Centre.

PMID- 9536626
TI  - The English sweating sickness, 1485-1551: a viral pulmonary disease?

PMID- 9536627
TI  - "Take time by the forelock": the letters of Anthony Fothergill to James Woodforde
      1789-1813.

PMID- 9536628
TI  - [Danish physicians underestimate blood-borne transmission. A first case of HIV
      infection in a surgeon transmitted from a patient is documented].

PMID- 9536629
TI  - [The need of preoperative traction of hip-near fractures. A critical review].

PMID- 9536630
TI  - [DNA on a chip. The meeting between computer technology and biology].

PMID- 9536631
TI  - [Estrogen replacement to women treated for endometrial cancer].
AB  - Oestrogen replacement therapy in women treated for endometrial cancer has long
      been considered contra-indicated. Based on a review of the literature, which
      shows a low risk of recurrence during oestrogen replacement therapy in women
      treated for low-risk endometrial cancer, we advocate that this group of patients
      could be offered oestrogen replacement therapy and be provided with the benefits
      of prevention of cardiovascular disease and osteoporosis. Further studies are
      needed to investigate the survival and recurrence rates of high-risk patients
      treated with oestrogen replacement therapy.

PMID- 9536632
TI  - [Stab and cut lesions among general practitioners in the county of Funen].
AB  - In a questionnaire sent out to general practitioners (GP) in the County of Funen
      they reported a yearly incidence of lesions penetrating the skin of 1.2 per
      practitioner. Approximately half of these lesions were potentially infectious.
      Sixty percent of the lesions were due to accidents involving needles. Only 52% of
      the GPs with the risk of a potentially infectious lesion tried to prevent
      infection. We estimate that the risk of becoming infected with HIV or Hepatitis-B
      infection is very low. It is necessary to get GPs to change procedures in an
      attempt to minimize the risk.

PMID- 9536633
TI  - [Percutaneous blood exposure among Danish physicians. Mechanisms and prevention].
AB  - The study describes the mechanisms of percutaneous blood exposure (PCE) among
      Danish doctors and discusses rational strategies for prevention. Data were
      obtained as part of a nation-wide survey of occupational blood exposure. The most
      recent percutaneous or mucocutaneous exposure within the previous three months
      was described. Of 9375 doctors, 6005 (64%) participated. A total of 971 PCE were
      described. Inattentiveness contributed to 30.5%. Use of fingers rather than
      instruments was a contributing cause of 36.9% of 483 PCE on suture needles.
      Common concomitant causes in such cases (n = 199) were poor space in (30.2%) or
      view of (18.6%) the operation field. Of 689 PCE in surgical specialties, 17.4%
      were inflicted by colleagues. Up to 53.3% of PCE on hollow-bore needles could be
      attributed to unsafe routines only. In conclusion, education in safer working
      routines are needed in all specialties. Introduction of safer devices should have
      a high priority in surgical specialties, and should be considered in non-surgical
      specialties too.

PMID- 9536634
TI  - [Poor compliance with universal precautions among Danish physicians].
AB  - In a nation-wide survey among Danish doctors, the compliance and reasons for non
      compliance with universal precautions (UP) and the associated circumstances of
      mucocutaneous blood exposure (MCE) were studied. Of 9384 questionnaires, 6256
      (67%) were returned and 6005 were eligible for analysis. Only 35% complied with
      the basic principles of UP. Compliance with protective barrier use in surgical
      versus non-surgical specialties was: Gloves 63.0% and 23.4%, masks 55.2% and
      17.6% and protective eyewear 11.5% and 4.0% respectively. Common given reasons
      for non-compliance were: "Interferes with working skills", "forget", "wear
      spectacles", "not available", "too much trouble to get" or "gloves do not fit".
      Of 741 MCE described in detail, an estimated 84-98% were potentially preventable
      if appropriate barriers had been worn. More than half of MCE were preventable by
      two interventions only: Compulsory use of protective eyewear during operations
      and of gloves during insertion of peripheral i.v.-catheters. In conclusion
      compliance with UP is unacceptably low and the majority of MCE were potentially
      preventable if appropriate barriers had been worn.

PMID- 9536635
TI  - [Barotrauma in children and adults after flying. Prevalence and treatment with
      Otovent].
AB  - To prevent barotitis during descent in aviation, the ears have to be cleared
      several times by performing the Valsalva's manoeuvre. The manoeuvre is difficult
      for children to perform, and they are therefore at high risk of developing
      barotitis. The treatment of barotitis is either inflation by a Politzer balloon
      or myringotomy. An alternative treatment is autoinflation using the Otovent. This
      prophylaxis/treatment can be performed by the child with assistance from its
      parents as soon as or preferably before the descent has started. The prevalence
      of barotitis amongst 45 children and 49 adults in transit was found to be highest
      in children, 28%, compared with adults, 10%. Only 6% of the children with
      negative middle ear pressure after flight managed a successful Valsalva
      manoeuvre, whereas 33% could normalise the middle ear pressure by inflating the
      Otovent. In conclusion we recommend autoinflation using the Otovent set by
      children and adults who have problems clearing their ears during flight.

PMID- 9536636
TI  - [Occurrence of eardrum pathology in a cohort of adults born 1955].
AB  - The aim of this study was to estimate the prevalence of the different types of
      eardrum pathology in a cohort (cohort 1955) who were children before the era of
      ventilation tubes, and to compare these findings with the prevalence of eardrum
      pathology in a previous published cohort study on 222 children followed since the
      age of four years (cohort 1975) in the era of ventilation tubes. All inhabitants
      of Hillerod county born in 1955 were invited to a screening examination including
      otomicroscopy, tympanometry and audiometry. All eardrum pathology was recorded.
      In cohort 1955, 59% of 460 possible, attended the examination. In addition 9%
      returned a questionnaire enquiring their otologic history. In the cohort with no
      grommets, retraction of Shrapnell's membrane was found in 4% of the ears compared
      to 20% in the cohort with grommets. Tensa pathology was found in 6% of the ears
      in the old cohort and in 24% in the young cohort. Despite the increased attention
      to the diagnosis of secretory otitis, and the increased rate of surgical
      treatment, the prevalence of eardrum pathology seems to have increased. The
      reason for this increase is discussed.

PMID- 9536637
TI  - [A method for quality assurance in a community mental health center. Community
      psychiatry in Copenhagen].
AB  - The purpose was to describe a method for quality assurance in community mental
      health centres. Three psychiatrists and a multiprofessional treatment team
      conceived the method. The community mental health center--which was the basis for
      the work--was the Copenhagen centre for the sectors Vesterbro and Kongens
      Enghave. The target group for the centre is people with serious mental illness.
      The work is done according to the principles for clinical case managers. Data are
      registered in a national database in combination with the centre's own
      registration system. Eleven indicators for process quality and eight for outcome
      quality were selected. Measurement parameters for there indicators were defined.
      Criteria and standard were defined according to existing knowledge and the
      author's clinical experience. The necessary programs for calculating the value of
      the chosen standards are constructed. With the use of existing data and a limited
      extra registration it was possible to evolve a method for quality assurance in a
      community mental health centre.

PMID- 9536638
TI  - [Dysphagia as first symptom of myasthenia gravis].
AB  - We present a case story of a 70-year-old female, who went through several
      examinations, multiple paraclinical investigations and lost 15 kg in bodyweight
      over a six month period, before the diagnosis myasthenia gravis (MG) was made.
      Dysphagia was from the early phase her most prominent and persistent complaint.
      However, other symptoms, thought to be allergic reactions, made the diagnosis
      difficult. The patient's symptoms are discussed. Most of these are consistent
      with MG, but on the other hand rare at the beginning of the disease. This report
      is a reminder that MG may present as dysphagia, addressed in particular to
      otolaryngologists and gastrosurgeons.

PMID- 9536639
TI  - [Kawasaki syndrome in an adult].
AB  - Kawasaki syndrome (KS) is an acute, febrile, exanthemous illness characterized by
      vasculitis of unknown origin mostly seen in children younger than four years of
      age. We describe a 24-year-old white male who fulfilled the diagnostic criteria
      for KS. In addition to the diagnostic symptoms of KS this patient had symptoms
      from the liver and lungs.

PMID- 9536640
TI  - [DNA microchips: after a revolution in biotechnology with great clinical and
      scientific possibilities].

PMID- 9536641
TI  - [Virus simulates killer cells].

PMID- 9536642
TI  - [Trauma therapy in Denmark].

PMID- 9536643
TI  - [The alcoholic personality].

PMID- 9536644
TI  - [Quality of life, resignation and survival].

PMID- 9536646
TI  - Effect of Indian red scorpion (Mesobuthus tamulus concanesis, Pocock) venom on
      thyroxine and triiodothyronine in experimental acute myocarditis and its reversal
      by species specific antivenom.
AB  - Acute myocarditis was induced in dogs and rabbits by injection of scorpion (M.
      tamulus concanesis, earlier called Buthus tamulus) venom by s.c., i.m. or i.v.
      routes. A decrease in thyroxine (T4) levels was observed following i.v. injection
      of venom in dogs. In rabbits the venom (i.m.) did not elicit any change in T4
      levels. Envenomation (s.c.) resulted in a reduction in triiodothyronine (T3)
      levels in dogs. Venom injection (s.c.) along with i.v. administration of the
      species specific antivenom (AScVS) did not cause any change in T3 and T4 levels
      in general. However an increase in T3 levels following AScVS was observed in
      envenomated dogs. The results suggest that scorpion envenomation caused an
      autonomic storm releasing massive amounts of catecholamines, angiotensin II,
      suppressed insulin secretion and reduced circulating T4 and T3 levels. Decrease
      in thyroid hormones results in fall in body temperature. Changes in the body
      temperature may increase the sensitivity of the scorpion venom and influence the
      course of toxicity.

PMID- 9536645
TI  - Newer thrombolytic drugs for acute myocardial infarction.
AB  - Arterial thrombosis is the underlying cause of a wide variety of cardiovascular
      diseases such as myocardial infarction, stroke and pulmonary thromboembolism. All
      the currently used thrombolytic agents are plasminogen activators, which are very
      efficient in restoring the blood flow. The fibrinolytic system comprises an
      inactive proenzyme plasminogen, that is converted by plasminogen activators to
      the enzyme plasmin, that degrades fibrin. Despite the widespread use of
      established thrombolytic agents such as streptokinase, tissue-plasminogen
      activator and urokinase, all these agents suffer from a number of inadequacies
      including resistance to reperfusion, occurrence of acute coronary reocclusion and
      bleeding complications. The quest continues for thrombolytic agents with a higher
      potency, specific thrombolytic activity and fibrin selectivity. Several lines of
      research towards improvement of thrombolytic agents are being explored including
      the construction of mutants and variants of plasminogen activators, chimeric
      plasminogen activators and conjugates of plasminogen activators with monoclonal
      antibodies. Newer molecules such as pro-urokinase, saruplase, alteplase, K1K2Pu
      and staphylokinase have shown promise in animal models of arterial and venous
      thrombosis and also in pilot scale clinical studies in patients with myocardial
      infarction. However, more clinical trials are needed to determine whether these
      novel recombinant thrombolytic agents shows improved efficacy and fibrin
      specificity with minimal bleeding tendencies.

PMID- 9536647
TI  - Zinc, copper and hydrolytic enzymes in epididymis of hydrocortisone treated rat.
AB  - Administration of glucocorticoid (1, 2 and 4 mg) in excess leads to degeneration
      of epididymides as supported by cellular degeneration, sperm density and
      morphometric measurements. Zinc level increased statistically after 1, 2 and 4 mg
      hydrocortisone treatment while copper increased after 1 and 2 mg treatment.
      Cholesterol, protein and leucine aminopeptidase levels increased and decreased
      significantly in caput and cauda respectively. Activity of alkaline phosphatase
      reduced significantly while the treatment of hydrocortisone at different doses
      elevated acid phosphatase, aryl sulphatase and lactate dehydrogenase activities.
      Evidently, these changes are as a result of onset of cellular degeneration
      leading to impairment of metabolic/secretory activity of epididymal cells. The
      possible involvement of pituitary-testis axis in hydrocortisone induced
      epididymal degeneration and functional inhibition has been discussed.

PMID- 9536648
TI  - Male reproductive toxicity of phosphamidon: histopathological changes in
      epididymis.
AB  - Phosphamidon, a neurotoxic insecticide, was tested for male reproductive toxicity
      with special reference to the epididymis. The insecticide was fed to Wistar
      strain male albino rat at 35 ppm concentration in drinking water ad libitum for
      30 days. After vascular perfusion, thin slices of caput and cauda epididymidis
      were embedded in plastic, cut at 1 micron thickness and stained in toluidine blue
      for light microscopic observation. Principal cells of the caput epididymidis were
      vacuolarized and seen to pinch off fragments apically. In the proximal cauda the
      clear cells increased in height and in the size of the secondary lysosomal
      granules. In the distal cauda the clear cells appeared swollen out of proportion.
      Phosphamidon appears to affect the principal cells indirectly through its toxic
      effect on the Leydig cells; the clear cells of the cauda appear to be directly
      vulnerable to the toxic action of the pesticide.

PMID- 9536650
TI  - Effect of chloride and diamide on angiotensin converting enzyme from sheep testis
      and epididymis.
AB  - Effect of chloride and diamide on testicular and epididymal angiotensin
      converting enzyme (ACE) activity was investigated using Hip-His-Leu as substrate
      in sheep. The chloride ions functioned as ACE activators, however, there was no
      linear correlation between the two. The optimum chloride concentrations were 500
      mM for epididymal ACE and 900-1100 mM for testicular ACE. Further, optimum
      chloride concentration increased ACE activity of testis and epididymis 25.40-
      folds and 12.84- folds respectively of the activities at physiological chloride
      concentration. The differences found in the effect of chloride on testicular and
      epididymal ACE activity suggest dissimilar three dimensional structure of ACE in
      these tissues. Increased testicular and epididymal ACE activity on diamide
      pretreatment indicates that tissue oxidation may affect ACE activity.

PMID- 9536649
TI  - Effect of edifenphos on follicular dynamics in albino rats.
AB  - Exposure of rats to 0.1, 0.15 and 0.20 mg/100 g body weight edifenphos (i.p.) had
      no significant effect on the number of healthy follicles and atretic follicles in
      all the stages. However, treatment with 0.25 mg dose resulted in a significant
      decrease in stage I and total number of healthy follicles and increase in stage V
      atretic follicles. A significant decrease in stage I, II, III and total number of
      healthy follicles, and a significant increase in stage I, III, IV and total
      number of atretic follicles were observed in 0.3 mg edifenphos treated rats. The
      results indicate that the effect of edifenphos is dose dependent.

PMID- 9536651
TI  - Permeability characteristics of piperine on oral absorption--an active alkaloid
      from peppers and a bioavailability enhancer.
AB  - Piperine, [1-[5-[1,3-benzodioxol-5-yl]-1-oxo-2,4, pentadienyl] piperidine], is a
      pungent alkaloid present in Piper nigrum Linn, and P. longum Linn. It is shown to
      enhance the bioavailability of various structurally and therapeutically diverse
      drugs. A concise mechanism responsible for its bioavailability enhancing action
      is poorly understood. This study is an effort to understand the absorption
      dynamics of piperine in intestine on oral absorption. It encompasses intestinal
      everted sacs as an experimental model. Cycloheximide treatment and exclusion of
      Na+ salts from incubating medium were the variables used. Absorption half life,
      absorption rate, absorption clearance and apparent permeability co-efficient were
      computed from the data. Experiments to denote physico-chemical characteristics of
      this moiety exhibited that it is a weak base, highly lipophilic in nature with
      partial solubility in aqueous media. It exhibited passive diffusion constituting
      non-saturable absorption kinetics. Transport of piperine was not resisted by UWL
      and was proposed to be absorbed through transcellular pathway. It displayed short
      absorption clearance and high apparent permeability co-efficient. Data thus
      obtained suggested that piperine is absorbed very fast across the intestinal
      barrier. It may act as an apolar molecule and form apolar complex with drugs and
      solutes. It may modulate membrane dynamics due to its easy partitioning thus
      helping in efficient permeability across the barriers.

PMID- 9536652
TI  - Effect of nimodipine on the efficacy of commonly used antiepileptic drugs in
      rats.
AB  - Effect of nimodipine was studied alone and in combination with phenytoin and
      valproate in maximal electroshock seizures in rats. The test drug was injected
      i.p. and seizures elicited by a 60 Hz alternating current of 150 mA intensity for
      0.25 sec duration through corneal electrodes. The median effective dose (ED50) of
      phenytoin, valproate and nimodipine were found to be 13, 255 and 4 mg/kg
      respectively. Addition of ED50 of nimodipine to ED50 of phenytoin and valproate
      produced an additive effect. Addition of ED25 of nimodipine to ED25 of phenytoin
      and valproate produced asynergistic effect. Our results show that addition of
      nimodipine significantly potentiates the anticonvulsant efficacy of phenytoin and
      valproate.

PMID- 9536653
TI  - Biochemical and histopathological changes in respiratory system of rats following
      exposure to diesel exhaust.
AB  - Effect of exposure to diesel exhaust (DE) for different durations was evaluated
      using histopathological and biochemical parameters in respiratory system of the
      rats. Animals were exposed to 1 part DE diluted with 5 parts of clean air in a
      simulation chamber for 15 min/day for 1, 7, 14 and 21 days. After completion of
      various exposures, biochemical parameters including elastase inhibitory capacity
      (EIC) and protein content of the bronchial airway lavage (BAL) and
      histopathological changes along with lung/body weight ratio were assessed. The
      elastase inhibitory capacity (an index of the protection against destruction of
      elastin, a lung connective tissue) was maximum at 1 week indicating thereby that
      the body renders protection against injury by increasing EIC levels in the
      initial phase. However, protein content in the BALF increased after 1 week and
      reached maximum at 2 weeks. Histopathological changes followed similar time
      course of pattern with accumulation of macrophages and protein exudation.
      Prolonged exposure up to 3 weeks, however was accompanied by chronic inflammatory
      changes and thickening of alveolar septa and blood vessels. Changes in lung/body
      weight ratio and suspended particulate matter (SPM) deposited on filters
      (simulation chamber) correlated well with EIC, protein content in BALF and
      histopathological changes. The biochemical findings accompanied with chronic
      structural changes in the lungs of rats following exposure to DE could be
      relevant to the clinical observation of increased incidence of chronic lung
      diseases after continued DE exposure.

PMID- 9536654
TI  - Antiperoxide effect of garlic protein in alcohol fed rats.
AB  - Rats fed ethanol (3.76g/Kg body wt/day) for about 45 days exhibited high levels
      of tissue malondialdehyde, hydroperoxide and diene conjugates. Activity of tissue
      superoxide dismutase, catalase, and glutathione content decreased. Administration
      of water soluble proteins of garlic (500 mg/kg body wt/day) to alcohol fed rats
      showed significant increase in antiperoxide activity and decrease in the activity
      of glutathione peroxidase and glutathione s transferase as compared to a standard
      drug gugulipid (50 mg/kg body wt/day).

PMID- 9536655
TI  - Antigenic structure of foot and mouth disease virus type A22 (Indian isolates).
AB  - Variations in foot and mouth disease virus are due to amino acid substitutions in
      the VP1, which is a major immunogen. Analysis of this hypervariable region is
      essential to know the antigenic structure of the serotype and is necessary to
      select a suitable vaccine strain. FMDV type A22 is one of the four prevailing
      virus types for which the vaccine is used regularly. To understand the antigenic
      structure of this type, carboxy- terminal region of VP1 from two field isolates
      and vaccine virus were sequenced and analysed. The results indicate that, Indian
      A22 has distinct antigenic structure.

PMID- 9536656
TI  - Activity of bacterial phosphomonoesterases in batch culture.
AB  - The phosphomonoesterases catalyse the hydrolysis of primary esters of phosphoric
      acid which help the bacteria to survive in phosphate stressed environment. Ninety
      five bacterial isolates were obtained from domestic sewage and industrial
      effluents of gelatine and soap factories at Jabalpur on a medium enriched with
      phosphate and were screened for phosphatase production. The phosphatase producers
      were tentatively identified as Escherichia coli, Vibrio vulnificus, Aeromonas
      hydrophila, Staphylococcus aureus, Pseudomonas maltophilia and Micrococcus
      varians. The in vitro studies on the production of phosphomonoesterases by
      bacteria was conducted. The maximum alkaline phosphatase production was recorded
      on 8th day of incubation by E.coli and P.maltophilia, on 10th day of incubation
      by V.vulnificus while M.varians and P.maltophilia produced higher acid
      phosphatase on 4th and 10th day of incubation respectively. The detailed
      investigations were done to find out the effect of various physical and chemical
      factors on phosphomonoesterases activity and the optimum conditions required for
      enzyme activity.

PMID- 9536657
TI  - Antibacterial activity of the antiinflammatory agent diclofenac sodium.
AB  - Antimicrobial property of ten antiinflammatory drugs was tested with eleven
      sensitive bacteria belonging to both Gram positive and Gram negative types. Since
      most of the bacteria were moderate to highly sensitive to diclofenac (Dc), this
      compound was tested in vitro against 397 bacteria, most of which were inhibited
      by Dc at 50-100 micrograms/ml level. When tested in vivo, Dc at 1.5 and 3.0
      micrograms/g body weight of a Swiss strain of white mice, could significantly
      protect the animals challenged with 50 MLD of Salmonella typhimurium NCTC 74.
      According to chi 2 test the in vivo data were highly significant (P < 0.001).

PMID- 9536659
TI  - Azo reductase activity of microbial population from gastrointestinal tract
      segments of various animals species.
AB  - Azo reductase activity of microbial population of stomach, small intestine,
      caecum and large intestine of different animals was investigated. There was low
      activity in stomach flora of wistar rat and 3 strains of mice. Flora of proximal
      portion of small intestine in different species revealed that carnivorous animals
      exhibited maximum activity followed by grazing animals. Maximum activity in
      middle portion of small intestine was noted in dog (98.2%), while minimum was
      observed in guinea pig (23.3%). Majority of test animals revealed maximum floral
      azo reductase activity (58-98%) in caecum. Activity in proximal portion of large
      intestine was highest in dog while pigeon and guinea pig had least activity (23.3
      27.1%). Appreciable microbial activity in distal end of large intestine was noted
      in sheep and goat. In all the 15 animal species investigated caecum showed
      maximum activity followed by pre and post caecal segments while stomach possessed
      the least. The results suggest that inter-species differences exist in microbial
      reductive activity which may be due to variation in composition and distribution
      of GI tract microflora and thus can influence toxicological implication of
      various dyes.

PMID- 9536660
TI  - Influence of caffeine on pharmacokinetic profile of sodium valproate and
      carbamazepine in normal human volunteers.
AB  - The present study evaluates effect of pharmacokinetic interaction between
      caffeine (300 mg) in three divided doses with sodium valproate (400 mg) and
      carbamazepine (200 mg) given as single doses, in normal human volunteers, using a
      open cross over design. Both the serum concentration of sodium valproate and
      pharmacokinetic parameters remained unaltered, as against significant reduction
      in plasma concentration and area under the concentration curve of carbamazepine
      following the coadministration of caffeine. Also, the plasma t 1/2 (of
      carbamazepine was prolonged by two folds and bioavailability reduced by about 32%
      in presence of caffeine. The results are of clinical significance as xanthine
      consumption may have to be restricted in patients on carbamazepine therapy and
      this aspect may need further investigation.

PMID- 9536661
TI  - Dose-related proconvulsant and anticonvulsant activity of isatin, a putative
      biological factor, in rats.
AB  - Isatin (indole-2, 3-dione) is an endogenous compound with anxiogenic properties,
      which occur within a narrow dose range (15-20 mg/kg, i.p.). Dose increment beyond
      50 mg/kg, i.p. leads to the loss of anxiogenesis. Since a link has been
      postulated between anxiogenic and convulsant activity, the effect of a range of
      doses of isatin (20-80 mg/kg, i.p.) was investigated on subconvulsant and
      convulsant doses of two seizure-inducing agents, namely, pentylenetetrazole (PTZ)
      and 3-mercapto-propionic acid (3MPA) in rats. Isatin was found to induce a dose
      related effect on PTZ and 3MPA convulsions. The lower dose (20 mg/kg, i.p.)
      potentiated PTZ and 3MPA convulsions, a median dose (40 mg/kg, i.p.) had
      insignificant effect, whereas higher doses (60 and 80 mg/kg, i.p.) of isatin
      exhibited significant anticonvulsant effect against both PTZ and 3MPA induced
      clonic convulsions. The investigation, thus, supports the contention that
      anxiogenic agents increase the susceptibility to chemical seizures. The
      proconvulsant effect of isatin, may be due to its inhibitory effect on central
      atrial natriuretic peptide receptors and stimulation of 5-hydroxytryptamine3 (5
      HT3) rather than its monoamine oxidase (MAO) B inhibitory action. The
      anticonvulsant effect on higher doses of isatin, on the contrary, may be induced
      by its metabolites, including 5-hydroxyisatin.

PMID- 9536662
TI  - Medication safety. Avoiding drug interactions.

PMID- 9536663
TI  - Complementary medicine. Chinese acupuncture gets nod from the west.

PMID- 9536664
TI  - "I've heard there is a new pill to treat hair loss. Is it better than Rogaine"?

PMID- 9536665
TI  - Obsessive-compulsive disorder. Giving up the secret.

PMID- 9536666
TI  - New estrogen may hold greater appeal.

PMID- 9536667
TI  - Weight and longevity.

PMID- 9536668
TI  - Fish and the heart.

PMID- 9536669
TI  - Nurses' pay award to be staged yet again.

PMID- 9536670
TI  - Nurses need improved working conditions.

PMID- 9536671
TI  - Diabetic control in the patient with acute myocardial infarction.
AB  - Diabetes mellitus affects 2% of the population and up to 5% of people over 65
      years of age (Thomas, 1993). Diabetic patients have more coronary artery disease
      and a higher mortality from acute myocardial infarction (AMI) than the rest of
      the population (Patmore and Jennings, 1996). They have similar-size infarcts to
      those without diabetes, but the total mortality post-MI is higher (Karlson et al,
      1993). This article examines the literature on AMI in diabetic patients to
      ascertain the most effective management of these patients and hence improve their
      prognosis.

PMID- 9536672
TI  - An introduction to the reading of electrocardiograms.
AB  - This article introduces the basic principles of reading electrocardiograms (ECGs)
      for nurses who are unfamiliar with reading them. For more experienced
      practitioners there are a number of useful articles and books (e.g. Hampton,
      1992a, b) that will help further their knowledge. The ECG records cardiac
      electrical activity as a graph; interpretation is illustrated here by sinus
      rhythm. A single ECG lead (lead II) is used throughout this article. Atrial
      fibrillation is described to show a contrasting dysrhythmia. Specific nursing
      care is suggested for patients being monitored or having ECGs taken.

PMID- 9536673
TI  - Educating nursing home staff in the reduction of pressure sores.
AB  - Care-related work within continuing care settings is often perceived as being of
      low status and requiring little skill. In reality, however, creating a positive
      long-term care environment requires imagination and creativity. Education and
      training are a key element in any effort to improve the quality of care in
      nursing homes and similar settings, yet recent evidence suggests that
      opportunities for continuing education and training for staff in such
      environments are limited. This article considers the context of continuing
      education for nurses and care assistants employed in nursing homes, and uses a
      pilot evaluation of an educational package aimed at reducing the incidence of
      pressure sores as a case example to raise important issues. The difficulties in
      providing sufficient opportunities for education are highlighted and the need to
      embed any educational programme within a well-developed staff support structure
      is stressed.

PMID- 9536674
TI  - Cancer of the prostate. 1: Promoting men's healthcare needs.
AB  - This three-part series explores the nurse's role in promoting men's health with
      regard to cancer of the prostate. This article presents the incidence of
      prostatic cancer and its relationship to geographical environment. Diagnosis,
      early detection and screening are also discussed and the possible contribution of
      diet to the rising incidence of the disease is examined. In the next article
      health education models and the role of the nurse are described and
      recommendations for practice are offered.

PMID- 9536675
TI  - Critical thinking and analysis: a model for written assignments.
AB  - The purpose of this article is to propose a model for critical analysis which can
      be incorporated into nurse education to enhance nurses' understanding of the
      concepts and to assist students in undertaking academic assignments. It provides
      a definition and conceptualization of critical thinking and critical analysis,
      and highlights the differences, similarities and interrelationships between them.
      The model suggests that there are 10 components of critical analysis. This
      provides the first step for developing further research on the content of the
      model, i.e. certain components are accepted and those which are unsuitable are
      rejected. The model assists the development of educational strategies to promote
      critical analysis skills, which are an essential element of the autonomous,
      critical thinking nurse practitioner.

PMID- 9536676
TI  - The Improtec range of pressure-relieving mattresses and overlays.
AB  - Increasing knowledge of the pathophysiology of pressure sores influences our
      thoughts on the best methods of meeting the Department of Health (1993) target of
      a 5-10% reduction in the incidence of pressure sores. Elderly people are one of
      the most at-risk groups as they tend to suffer disproportionately from
      neurological and cardiovascular disease. Patients suffering with shock,
      dehydration and prolonged hypothermia due to some traumatic event feature high on
      the at-risk category, especially if the patient lies for any period of time on an
      unprotected accident and emergency (A&E) or theatre trolley. Spenco Healthcare
      International has developed Improtec, a specially designed range of high-quality,
      cost-effective products for use in (A&E) units, treatment rooms, operating
      theatres, hospital wards and the community.

PMID- 9536677
TI  - The standard of nursing records should be raised.

PMID- 9536678
TI  - [Meeting a missionary in Venezuela].

PMID- 9536679
TI  - [Topic: nursing process. Report on the teaching of nursing process during the
      course of 1997 at the School of Pediatric Nursing of the Johannes Gutenberg
      University in Mainz].

PMID- 9536680
TI  - [Gentle care of the premature].

PMID- 9536681
TI  - [Confidentiality in the health professions and protection of data].

PMID- 9536682
TI  - [Care of children during high-frequency oscillation ventilation].

PMID- 9536683
TI  - [Motivation and psychological suitability for work in a pediatric intensive care
      unit].
AB  - During interviews with physicians and nurses on the general pediatric intensive
      care unit (ICU) of the University of Heidelberg Children's Hospital personnel
      reported on various aspects of their work. One complex of questions dealt with
      the motivation to work in intensive medicine. Physicians and nurses showed
      different patterns of motivation. Physicians could be clearly divided into those
      who found intensive medicine fascinating and those who tended to fear it. Nurses'
      motivation is multifaceted and differentiated. The information gained from the
      interviews questions the sense of obligating physicians without interest or
      aptitude to rotate to an ICU during their specialty training in pediatrics. This
      policy is associated with corresponding risks for patients. The work of often
      superiorly qualified nurses becomes more difficult.

PMID- 9536684
TI  - [Still birth].

PMID- 9536686
TI  - [Hear the children cry. Emotional abuse of children].

PMID- 9536685
TI  - [A confinement, conducive to breastfeeding].

PMID- 9536687
TI  - [Ecstasy--adolescents and drugs].

PMID- 9536688
TI  - [Didactic guidelines and practical instructions in the treatment of a child with
      bronchial asthma].

PMID- 9536689
TI  - [The former prematures. 4. Deike].

PMID- 9536690
TI  - [Necessity is the mother of invention. Home care then and now].

PMID- 9536691
TI  - [Organization by coordination and cooperation].

PMID- 9536692
TI  - [Home care for Holderlin].

PMID- 9536693
TI  - [Urinary incontinence in women--clinical aspects and therapy].

PMID- 9536694
TI  - [The opinion of patients in a psychiatric hospital on their drug therapy].

PMID- 9536695
TI  - [Better understanding of the psychological situation of cancer patients. The best
      medicine for people is people (Paracelsus)].

PMID- 9536696
TI  - [How much skin care do patients need?].

PMID- 9536697
TI  - [A nurse is complaining: care or neglect?].

PMID- 9536698
TI  - [Differences in the activity of gestagens. The effects of gestagens in the pill
      on skin, hair and body weight].

PMID- 9536699
TI  - [Valuable tips for the quality of life. Help in the profession of living].

PMID- 9536700
TI  - [Psychologists who created a school (I). Sigmund Freud].

PMID- 9536701
TI  - [Ethics. What can we know? What should we do? What may we hope for?].

PMID- 9536702
TI  - Nursing management has been reviewing it's performance recently.

PMID- 9536703
TI  - Business planning.

PMID- 9536704
TI  - Local development.

PMID- 9536705
TI  - Finance and accounting applications in nursing and clinical services. Part 2.

PMID- 9536706
TI  - Karen Parsley. Interview by Tom Keighley.

PMID- 9536707
TI  - Integrated care management.

PMID- 9536708
TI  - Supervise to practise.

PMID- 9536709
TI  - Restoring independence.

PMID- 9536710
TI  - Coping with redundancy.

PMID- 9536711
TI  - NHS are still trying to decipher the new code.

PMID- 9536712
TI  - The leadership challenge in nursing.

PMID- 9536713
TI  - Change? no problem.

PMID- 9536714
TI  - Clinical supervision for forensic mental health nurses.

PMID- 9536715
TI  - The interview--Callista Roy. Interview by Tom Keighley.

PMID- 9536716
TI  - New ways for new staff.

PMID- 9536717
TI  - Transforming ourselves.

PMID- 9536719
TI  - Care in the community needs reforming?

PMID- 9536718
TI  - Bed blocking.

PMID- 9536720
TI  - Bart's has been reprieved. Interview by Mark Gould.

PMID- 9536721
TI  - Smoking out the policies.

PMID- 9536722
TI  - Bugged by the future.

PMID- 9536723
TI  - Every nurse's worst nightmare.

PMID- 9536725
TI  - Gro Harlem Brundtland could be the person to restore stability and credibility to
      the World Health Organization.

PMID- 9536724
TI  - Mental health crisis in the capital.

PMID- 9536726
TI  - Boys as young as 10 were accused of rape has disturbing implications for all
      professionals who work with children.

PMID- 9536727
TI  - Moonlighting: a student's lot?

PMID- 9536728
TI  - Mouth care-1.

PMID- 9536729
TI  - The cost of caring.

PMID- 9536730
TI  - Facts of life.

PMID- 9536731
TI  - In sickness and in health.

PMID- 9536732
TI  - A place to grieve.

PMID- 9536733
TI  - The review of the 1979 Nurses, Midwives and Health Visitors Act.

PMID- 9536734
TI  - Respiratory system: Part 1. Pneumonia.

PMID- 9536735
TI  - Genital warts: their etiology and treatment.
AB  - This article continues our series looking at the most common sexually transmitted
      infections. The risk factors, incidence and treatment of genital warts are
      explained and the care of the patient is described. A case study completes the
      overview.

PMID- 9536736
TI  - Preparations for skin conditions.
AB  - The major skin preparations listed in the Nurse Prescribing Formulary involve the
      treatments for dry and damaged skin, dermatitis, eczema, and nappy rash. These
      preparations are described and their actions discussed. In order to appreciate
      how each of the preparations work, the article begins with an examination of the
      anatomy and physiology of the skin. The effects of emollients and barrier creams
      on the skin are then discussed.

PMID- 9536737
TI  - Osteoporosis: learning together.
AB  - This article outlines the planning and setting up of an advice and discussion
      group for people with osteoporosis and their families to give a fuller
      understanding of the condition and how to manage it.

PMID- 9536738
TI  - The history and use of the Waterlow card.

PMID- 9536739
TI  - Wound care. Unity in practice.

PMID- 9536740
TI  - Wound care. Peak performance.

PMID- 9536741
TI  - Wound care. Ulcer update.

PMID- 9536742
TI  - Wound care. Under the skin.

PMID- 9536743
TI  - A way through the maze.

PMID- 9536744
TI  - There are not enough opportunities for nurses to develop their roles.

PMID- 9536745
TI  - Sterling work.

PMID- 9536746
TI  - Savvy makes cents.

PMID- 9536747
TI  - A world of opportunities.

PMID- 9536748
TI  - Small change.

PMID- 9536749
TI  - Nurse, there's a fly on my wall.

PMID- 9536751
TI  - Casualty watch.

PMID- 9536750
TI  - Should A&E nurses shop patients who may be criminals.

PMID- 9536752
TI  - Statements on how to tackle world poverty are laudable.

PMID- 9536753
TI  - Frank being frank. Interview by Rachel Sylvester.

PMID- 9536754
TI  - In the bleak midwinter.

PMID- 9536755
TI  - Fast-track slips.

PMID- 9536756
TI  - The 30-minute promise.

PMID- 9536757
TI  - Blockage in the system.

PMID- 9536758
TI  - Lured by the great outdoors.

PMID- 9536759
TI  - Kiss and hell.

PMID- 9536760
TI  - All in a day's work.

PMID- 9536761
TI  - Smoke signals.

PMID- 9536762
TI  - Flying colours. Interview by Sue Smith.

PMID- 9536763
TI  - Catch 'em young.

PMID- 9536765
TI  - Many people think self-injury is just a form of attention-seeking.

PMID- 9536766
TI  - Chlamydia: the most common sexually transmitted infection.
AB  - This article is the third in our series on sexually transmitted infections. The
      epidemiology and signs and symptoms of chlamydia are described and diagnostic
      tests, treatments, and health education and promotion are discussed.

PMID- 9536767
TI  - Oral analgesics: aspirin and paracetamol.
AB  - This article is the third in a series of six looking at the knowledge needed for
      nurses prescribing. The mode of action, use and side-effects of oral analgesics
      are considered and drug interactions are also described.

PMID- 9536768
TI  - Atypical neuroleptics: use for schizophrenia.

PMID- 9536769
TI  - Moving and handling in the community.

PMID- 9536770
TI  - Change from the bottom up.

PMID- 9536771
TI  - An assessment of need for district nursing.
AB  - The north London Borough of Barnet has a population of just over 300,000 people,
      a large proportion of whom are over the age of 75. In the summer of 1995, as a
      result of the shifting emphasis within the NHS from secondary to primary care, it
      was recognised that the district nursing service was under pressure to meet the
      needs of the population. Primary Care Development Fund money was identified for
      new investment in the service. A health visitor researcher was seconded to the
      Public Health Directorate to undertake a needs assessment of district nursing for
      the borough. A qualitative research method was used in the form of focus groups
      of district nurses to assess their perceived needs for the services. These needs
      were prioritized and recommendations made. An additional 13 nurses (whole-time
      equivalents) of various grades in specific areas of the borough were subsequently
      employed.

PMID- 9536772
TI  - The right stuff.

PMID- 9536773
TI  - Flying your colours.

PMID- 9536774
TI  - When knowledge is power.

PMID- 9536775
TI  - [Dying today].

PMID- 9536776
TI  - [When the farewell approaches. Social work with the dying and their families].

PMID- 9536777
TI  - [The computer as an instrument for nursing--does it exist?].

PMID- 9536778
TI  - [Dying and death in the hospital].

PMID- 9536779
TI  - [Caring in grief].

PMID- 9536781
TI  - [To die living--hospice. A contribution to the daily work at the Vienna Mobile
      Caritas Hospice].

PMID- 9536780
TI  - [Caring for severely ill patients until their death].

PMID- 9536782
TI  - [Explantation of a cadaver--experiences and feelings].

PMID- 9536783
TI  - [Dignified care to the end ... nursing students from the Klagenfurt Nursing
      School report on their experiences with dying patients and the hospice idea in
      nursing].

PMID- 9536784
TI  - [Factors influencing the utilization of social services in old age].
AB  - This study investigates factors influencing the utilization of social services in
      old age. Medical, social and psychological variables are analyzed among a group
      of 641 community-dwelling elderly people. Furthermore, this article examines
      whether utilization of social services differs in different socio-economic living
      conditions. Results show that the use of services is affected by indicators of
      independence, financial resources and the informal support system. There is only
      little difference of using social services in different socio-economic living
      conditions, and this finding is explained by an interaction of medical, social
      and psychological variables.

PMID- 9536785
TI  - [Requirements for the definition of nursing terms from the viewpoint of nursing
      science].
AB  - Firstly the article develops requirements for definitions of nursing terminology.
      Secondly the Alpha-Version of the ICNP (International Classification of Nursing
      Practice), published in 1996, is examined according to these requirements. The
      author comes to the conclusion that the definitions developed on the basis of the
      ICNP do not suffice for the complexity and various dimensions of nursing practice
      and science.

PMID- 9536786
TI  - [The concept of paradigm in nursing science].
AB  - This paper critically analyses the use of the term paradigm in nursing science.
      The essay consists of two main sections. The "prekuhnian" meaning of the paradigm
      term is described in the first section. The developments in the philosophy of
      science are presented in conjunction with the rise of the "antipositivist turning
      point" and Kuhn's historical approach with its central terms (paradigm,
      revolution, normal science). Some central points of criticism regarding Kuhn's
      approach close the first section. The second section gives attention to the
      application of the term paradigm in nursing science, at first describing the
      situation in the USA and subsequently referring to Germany. The insufficient
      extent of discussions on questions and problems regarding the philosophy of
      science is elucidated in the following criticism. The examination comes to the
      conclusion that the application of the paradigm term to nursing science is
      neither possible nor is it sensible. A brief review of the prospects for nursing
      science concludes the essay.

PMID- 9536787
TI  - ["All that time we were working hand in hand ..." a comparative study on the
      effects of professionalization on German and American intensive care nurses].
AB  - The discussion about improving and reevaluating nursing education and nursing
      practice in Germany is often oriented at the US-american nurses' training. Here
      one finds a higher degree of professionalisation and university nursing programs.
      A German-US-American comparative study of 13 ICU nurses each analyzes what
      effects a higher degree of professionalism has on every day nursing practice.
      Using the data of structured interviews, dimensions of job perception and aspects
      of coping capabilities with stress in regard to patient care and relation with
      physicians of both nursing groups are compared. Results show that US-American
      nurses often refer to cognitive aspects of being in control of a situation and
      emphasize their professional part. When assessing their experiences they mainly
      describe actions they took emphasizing cooperation and help they gave each other.
      German nurses accentuate the emotional side, describing fear, anger, rage and
      helplessness. In their relations with physicians the US-American nurses are more
      likely to insist on their nursing competence, while German nurses tend to be
      annoyed, resignated, and try to withdraw from the situation. These differences
      are discussed in relation to the different nursing programs. The US-American
      education, stressing supervision and the ability to reflect upon one's action
      seems to have a positive influence on coping capabilities and enhance job
      satisfaction.

PMID- 9536789
TI  - [Gender and social class as categories in the history of nursing: male nurses in
      the professionalization of nursing in Germany around the year 1900].
AB  - At the turn of the century, the professionalization of German nursing was
      considerably accelerated. As a long-term result, nursing became a socially
      accepted occupation for middle-class women. This caused a process of social and
      sexual differentiation of the nursing staff, which is described below from the
      viewpoint of male nurses. Against this background, the categories "gender" and
      "class" are both significant in contemporary debates. They were at work at two
      levels: first, in perception and argumentation patterns and, second, as
      distinguishing features in the new institutions of professional nursing, i.e. the
      general hospitals and the professional organizations.

PMID- 9536788
TI  - [Independently offered care and health promotion--a vision of the future?
      Presentation and discussion of Erickson, Tomlin and Swain's Nursing Theory,
      describing a "nurse-managed wellness clinic" in the U.S.A].
AB  - The article presents Erickson, Tomlin & Swain's theory and paradigm of nursing
      and describes an example of its application in a nurse-managed wellness clinic in
      the USA. Interviews with the staff before and after a visit as a participant
      observer, as well as analyses of the project documentation provided information.
      The application of the theory in this practical setting is discussed. Emphasis is
      given to organizational structures that allow autonomy for nursing and therefore
      provide ideal conditions for the application of the nursing theory.

PMID- 9536790
TI  - [Nursing is education and needs sensitivity. The relationship between teaching
      and nursing].
AB  - There is no doubt: Active nursing as a profession needs training in many
      respects, in higher education, and--last but not least--needs intensive
      sensitivity. The author goes even further: Practice of nursing must be a specific
      part of education. Nursing is--likewise education--part of corporative life under
      special conditions and needs dialogue as a basis to acquire knowledge about the
      world. Being isolated from social life, from dialogue and self-acting means
      isolation and nonparticipating in reality.

PMID- 9536791
TI  - [Quantitative and qualitative studies: creating spaces, making science].
AB  - The text refers about polemics and controversies emerging out of quantitative and
      qualitative fields of studies. In a reflexive approach, the author weighs up
      equivocations and visualizes some adoptions of such approaches, keeping away from
      conceiving the privilege of only one path. Instead, she converges to the
      construction of spaces in face of the uncountable possibilities of making
      science. For that, she keeps in mind the coherence with the proposition of a
      study in which the researcher is mobilized.

PMID- 9536792
TI  - [Realization, affiliation and power: which one of these three factors is
      responsible for nurses' motivation in an university hospital?].
AB  - The nursing develops it's activities through the staff work, therefore, the
      quality of its work depends on the performance of the work group. For this
      reason, the nursing knowledge about human motivation and the different
      motivational factors which interfere in people actions are very important. For
      some persons is important to do things (realization necessity), for others, is
      important to influence people (power necessity), and for others to valorize the
      fellowship with the work group (affiliation necessity) is the most important. The
      present study is based on "three motives" of the McClelland (1965) approach. The
      authors also used the Souza (1972) model with the aim to identify which factors
      are responsible for nurses motivation in adults clinical wards in an university
      hospital. The results shows that Realization (80%) is the predominant
      motivational factor, the Affiliation and Power are in the second place with the
      same rate (7%).

PMID- 9536793
TI  - [Womens' view of caregiving. Implications for revisions of the concept].
AB  - The goal of the workshop "Caregiving and Companionship" was to provide women
      living in Porto Alegre with an opportunity to participate in a caregiving
      activity in which they could exchange ideas, get to know and talk about the
      meaning of the word caregiving as perceived both in an artistic and/or a
      scientific realm. Testimonies collected from a group of 60, shed light on the
      concept of the word. New directions, news dimensions were added to the meaning of
      maternity--which for women represents caregiving in its fullest and most well
      know sense. The workshop gave them a chance to reshape concepts, discover new
      potentials and share growth on a me to you basis, as a part of their daily
      endeavors.

PMID- 9536794
TI  - [Nurses' perception of management].
AB  - The objective of this investigation is to identify nurses perception about wards
      management. The collecting of the data was mode through an organized interview
      with sixteen nurses which works in patients wards in three hospitals of Porto
      Alegre. The data were examined based on the conteud analysis proposed by Bardin
      (1977). The results showed five categories: management conception, management
      characteristics, nurses activities, feelings and nursing graduation and induce us
      to do some reflexion about the curriculum modification, nurse-teachers
      improvement and the adjustment between the learning necessity and the work
      market. In this way is vital that professionals to look for best proficiency.

PMID- 9536795
TI  - [Paradigmatic changes in care caused by the experiences of pediatric nurses].
AB  - The aim of this study is revealing the work process development of nurses which
      works in the child care area and to understand how paradigmatical transformations
      of model and care occur from the daily experience. The participants were ten (10)
      nurses, all of them, females of long experience in the area of child care. This
      investigation follows the four steps indicated by Giorgi (1985) and Comiotto
      (1992). The results showed four phenomenological essences: building one's self;
      the discovery of the child care significance; the nurse as educator; the
      perception of the constant series of transformations. Starting from the essences,
      the phenomenological dimensions appear in number of fourteen (14). This work
      provided profound reflections about the relationship of the process and the act
      of care.

PMID- 9536796
TI  - [Diabetes mellitus: training of health teams at the university].
AB  - The authors describe their experience as a multiprofessional team working at two
      Basic Health Units (BHU) in Londrina city in 1995. The work involved medical,
      nursing students and residents. The goals were: a) to train BHU teams in the
      assistance of diabetic patients; b) expose students to teaching experiences at
      the BHUs, emphasizing multiprofessionality; c) to establish an hierarchy and
      provide suitable treatment for the BHUs diabetic clientele. A total of 106
      diabetic patients were assisted. The project involved 22 students and 37
      professionals. A questionnaire assessment indicated that the goals were achieved.
      The experience is considered valid as a teaching and inservice training.

PMID- 9536797
TI  - [In Rwanda: courage is back].

PMID- 9536798
TI  - [Nursing care during radiotherapy].

PMID- 9536799
TI  - [Risk of accidental exposure to blood in a biology laboratory].

PMID- 9536800
TI  - [What is meant by "introduction to research" for nursing students].

PMID- 9536801
TI  - [For an active and sporty retirement].

PMID- 9536802
TI  - [A lesson in the art of living. Interview by Ghislaine Trabacchi].

PMID- 9536803
TI  - [Autonomy/dependence: an evaluation scale. A method for the observation and
      evaluation of the loss of autonomy].

PMID- 9536804
TI  - [As the equilibrium goes, everything goes].

PMID- 9536805
TI  - [Music and the elderly: snapshots of the sessions].

PMID- 9536806
TI  - [A space for tenderness in a world of old age].

PMID- 9536807
TI  - [When institution and fun go together].

PMID- 9536808
TI  - [From childhood to old age, only one heart beat.... Interview by Odile Burrus].

PMID- 9536809
TI  - [The pretty story of Dolly and Polly, the lambs of the transgenic revolution].

PMID- 9536810
TI  - [Hospital architecture and hygiene: management of the utility rooms].

PMID- 9536811
TI  - [And you ... how much do you drink?].

PMID- 9536812
TI  - Low back pain: an intermittent and remittent predicament of life.

PMID- 9536813
TI  - Cryoglobulins are not essential.

PMID- 9536814
TI  - Soft tissue mass around the shoulder.

PMID- 9536815
TI  - Neuropsychiatric lupus?

PMID- 9536817
TI  - Unusual and memorable. Nodular erosive rheumatoid arthritis.

PMID- 9536816
TI  - On the course of low back pain in general practice: a one year follow up study.
AB  - OBJECTIVES: Knowledge on the clinical course of low back pain presented in
      general practice is poor. Preceding studies offer a fragmentary view only,
      whereas further knowledge is important to enable the assessment of the prognosis.
      The object of this study is to investigate the course of low back pain presented
      in general practice to enable the assessment of the prognosis. METHODS: A one
      year follow up study on the clinical course of low back pain in consecutive cases
      receiving usual care in general practice. During a period of two years 15 general
      practitioners from Amsterdam and surrounding areas included consecutive patients
      with both chronic and recent onset low back pain. After the initial visit, each
      patient was monitored for a period of 12 months. The follow up consisted of
      monthly postal questionnaires on the course of the low back pain and the related
      disability. RESULTS: A total of 443 of 605 patients identified were included in
      the follow up, which was fully completed by 269 patients. In general, patients
      with less serious low back pain participated less often or did not complete the
      follow up. At 12 weeks 35% and at the end of the follow up 10% of the population,
      respectively, still suffered from low back pain. Both the pain and the disability
      seemed to diminish quickly after the initial visit, and both seemed to stabilise
      at a lower level if the low back pain did not disappear completely. About three
      of four patients, whose pain disappeared before the end of the follow up, endured
      one or more relapses within a year. The median time to a relapse was about seven
      weeks, and its median duration about six weeks. Both the pain and the disability
      turned out to be less severe during relapses. The median time to recovery for
      patients whose low back pain developed more than seven weeks before the initial
      visit, was four weeks longer than for patients with more recently developed low
      back pain at the initial visit. CONCLUSIONS: The clinical course of low back pain
      presented in general practice, for the most patients, clearly is less favourable
      than expected. It takes more than just a few weeks to recover, and relapses occur
      within a year in most cases. Fortunately, both the pain and the disability
      quickly diminish, even if the low back pain does not resolve within a few weeks.

PMID- 9536818
TI  - Weak association between subjective symptoms or and objective testing for dry
      eyes and dry mouth: results from a population based study.
AB  - OBJECTIVES: To determine associations between symptoms of dry eyes and dry mouth
      and objective evidence of lacrimal and salivary gland dysfunction in a population
      based sample. To determine associations between these elements and the presence
      of autoantibodies. METHODS: A cross sectional population based survey. Subjects
      were interviewed and examined (Schirmer-1 test and unstimulated salivary flow)
      for the presence of dry eyes and mouth. Antibodies (anti-Ro [SS-A], anti-La [SS
      B], rheumatoid factor, antinuclear antibody) were measured. RESULTS: 341 subjects
      were examined. Twenty four per cent had dry eye symptoms, 29% dry mouth symptoms,
      and 14% both. There was only a weak association between the presence of oral or
      ocular symptoms and their respective test results. Associations were strongest
      between dry mouth symptoms and positive test results, and in subjects under 55
      years of age. There was no association between the presence of autoantibodies and
      either symptoms or signs of dry eyes or dry mouth. CONCLUSION: Only weak
      associations were found between self reported symptoms of dry eyes and dry mouth
      and objective measures said to define Sjogrens syndrome in the general
      population. The clinical significance of these symptoms in the community needs
      reappraisal.

PMID- 9536819
TI  - Effects of induced mast cell activation on prostaglandin E and metalloproteinase
      production by rheumatoid synovial tissue in vitro.
AB  - OBJECTIVE: To determine whether induced mast cell activation/degranulation in
      rheumatoid synovial explants modulates the production of prostaglandin E (PGE2),
      and the matrix metalloproteinases (MMPs) collagenase 1, gelatinase A, and
      stromelysin 1. METHODS: Synovial explant cultures were treated either with rabbit
      IgG anti-human IgE as a mast cell (MC) secretagogue or with non-immune rabbit IgG
      as controls. After 20 hours conditioned medium was assayed for the release of MC
      tryptase, PGE2, collagenase 1, gelatinase A, and stromelysin 1 using
      radioimmunoassay, enzyme linked immunosorbent assay, western blot, and zymogram
      techniques; tissue explants were examined immunohistologically for the relative
      distributions of MC tryptase, collagenase 1, and stromelysin 1. RESULTS: Over a
      20 hour incubation period the MC secretagogue treated explants showed a
      significant increase in the quantities of released tryptase and PGE2 compared
      with controls. By contrast, the three MMPs showed variable values between
      experiments in response to MC activation; no reproducible trend of either an
      increased or decreased production of each MMP over control values was evident.
      Each MMP initially appeared as an inactive precursor form; collagenase 1 and
      stromelysin 1 were more effectively processed to active forms in the MC activated
      cultures. Immunolocalisation studies of MC activated explants showed that areas
      of extracellular tryptase were commonly associated with the local production of
      both collagenase 1 and stromelysin 1. CONCLUSION: MC degranulation induced
      artificially in rheumatoid synovial explant cultures consistently resulted in an
      increased production of PGE2 but had variable effects on the quantification of
      released collagenase 1, gelatinase A, and stromelysin 1. Such observations
      support the concept that activated synovial MCs within their native environment
      stimulate the production of non-MC derived PGE2 and may contribute to the
      regulation and processing of specific MMPs; both aspects represent important
      components of the inflammatory and degradative processes of the rheumatoid
      lesion.

PMID- 9536820
TI  - Analysis of LMP and TAP polymorphisms by polymerase chain reaction-restriction
      fragment length polymorphism in rheumatoid arthritis.
AB  - OBJECTIVE: The aim of this study was to investigate the relation between the
      polymorphism of large molecular weight proteasome (LMP) (LMP2-LMP7) and
      transporter associated with antigen processing (TAP) (TAP1-TAP2) genes and
      rheumatoid arthritis (RA). METHODS: Sixty RA patients and 102 ethnically matched
      unrelated healthy subjects were typed for LMP, TAP, and disease associated HLA
      DRB1 alleles by using a new strategy based on polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP) with amplification created
      restriction sites. RESULTS: The polymorphism of LMP (LMP2-LMP7) and TAP (TAP1
      TAP2) genes was examined in shared epitope positive and negative RA patients and
      controls. No significant differences in the LMP or TAP allele frequencies were
      observed between the total patient and control groups or the patients and
      controls groups or the patients and controls positive or negative for the shared
      epitope. CONCLUSION: The data suggest that the polymorphisms of LMP and TAP genes
      do not have an important influence in the pathogenesis of RA, although larger
      studies will be needed to provide more conclusive evidence on the role of these
      genes in RA. A new, highly reliable strategy for typing LMP alleles is also
      described.

PMID- 9536821
TI  - Performance of the preliminary definition of improvement in juvenile chronic
      arthritis patients treated with methotrexate. Italian Pediatric Rheumatology
      Study Group.
AB  - OBJECTIVE: To investigate the performance of the core set of outcome measures and
      the preliminary definition of improvement (PDI) in the assessment of response to
      methotrexate (MTX) treatment in children with juvenile chronic arthritis (JCA).
      METHODS: Data were obtained from an open label, non-controlled trial designed to
      investigate the efficacy of MTX in children with JCA. All patients had the core
      set of variables assessed at baseline and after six months of treatment.
      Variables in the core set are: (1) physician global assessment of disease
      activity; (2) parent or patient (if appropriate in age) global assessment of
      overall well being; (3) functional ability; (4) number of joints with active
      arthritis; (5) number of joints with limited range of motion; (6) erythrocyte
      sedimentation rate. The PDI specifies that to be classified as improved, a
      patient must show at least 30% improvement from baseline in three of any six
      variables in the core set, with no more than one of the remaining variables
      worsening by more than 30%. RESULTS: A total of 111 JCA patients were included in
      the study. According to the PDI, after six months of MTX treatment 73 patients
      (66%) were classified as improved and 38 (34%) as not improved. Among the core
      set variables, parent assessment detected the highest percentage of patients
      improved (72%) and functional assessment the lowest (37%). CONCLUSION: The PDI
      identifies about two thirds of patients with JCA treated with low dose MTX as
      improved. This proportion is similar to that expected to improve based upon a
      previous controlled study of low dose, oral MTX and provides preliminary evidence
      of the definition's validity.

PMID- 9536822
TI  - Hepatitis G virus infection in primary Sjogren's syndrome: analysis in a series
      of 100 patients.
AB  - OBJECTIVE: To determine the prevalence and clinical significance of hepatitis G
      virus (HGV) infection in a large cohort of patients with primary Sjogren's
      syndrome (SS). PATIENTS AND METHODS: The study included 100 consecutive patients
      (92 female and eight male), with a mean age of 62 years (range 31-80) that were
      prospectively visited in our unit. All patients fulfilled the European Community
      criteria for SS and underwent a complete history, physical examination, as well
      as biochemical and immunological evaluation for liver disease. Two hundred
      volunteer blood donors were also studied. The presence of HGV-RNA was
      investigated in the serum of all patients and donors. Additionally, HBsAg and
      antibodies to hepatitis C virus were determined. RESULTS: Four patients (4%) and
      six volunteer blood donors (3%) presented HGV-RNA sequences in serum. HGV
      infection was associated with biochemical signs of liver involvement in two (50%)
      patients. When compared with primary SS patients without HGV infection, no
      significant differences were found in terms of clinical or immunological
      features. HCV coinfection occurs in one (25%) of the four patients with HGV
      infection. CONCLUSION: The prevalence of HGV infection in patients with primary
      SS is low in the geographical area of the study and HCV coinfection is very
      uncommon. HGV infection alone does not seen to be an important cause of chronic
      liver injury in the patients with primary SS in this area.

PMID- 9536823
TI  - Genetic anticipation in Behcet's syndrome.
AB  - OBJECTIVE: To examine the presence of genetic anticipation in families with
      Behcet's syndrome (BS). METHODS: A total of 18 families with 40 affected members
      in two successive generations were evaluated by interviewing them for their ages
      at the onset of the first symptom of BS and for their ages at the time they
      fulfilled the diagnostic criteria. RESULTS: It was noted that the age of onset of
      the first symptom was lower in the second generation in 14 families (p = 0.01)
      with a mean (SD) age of 20.57 (7.47) years in the children compared with 33.29
      (9.92) years in the parents (t = 7.79, p < 0.0001), whereas the diagnostic
      criteria were fulfilled at an earlier age in the children in 15 families (p =
      0.01) with a mean age of 21.2 (6.74) years in the children compared with 36.4
      (9.55) years in the parents (t = 7.41, p < 0.0001). CONCLUSION: Genetic
      anticipation was present in 15 of 18 (84%) of the families with BS in the form of
      earlier disease onset in the children compared with their parents.

PMID- 9536824
TI  - Analysis of T cell receptor V alpha polymorphisms in rheumatoid arthritis.
AB  - OBJECTIVE: To test for association of T cell receptor (TCR) V alpha polymorphisms
      and rheumatoid arthritis (RA) in British and Swiss white populations. METHODS:
      TCRAV polymorphisms were analysed in RA patients and controls by single strand
      conformational polymorphism (SSCP) analysis. Associations were sought between
      defined genotypes and RA, and the effect of HLA-DR4 status analysed. Putative
      associations were then retested further in new groups of patients and controls.
      Overall, 360 RA patients and 197 controls were studied. RESULTS: No association
      between TCRAV5S1, V6S1, V8S1, V17S1 or V21S1 polymorphisms and RA were observed
      in the initial population screened. Stratification for DR4 status showed an
      increase of V5S1*01/*01 in DR4 positive versus DR4 negative patients (chi 2 =
      7.19, p = 0.028 (2df), p = 0.14 after correction for multiple comparisons). This
      putative association was tested in three further patient groups, none of which
      showed significant increase of V5S1*01/*01 in DR4 positive patients, although an
      overall trend towards an increase in V5S1*01/*01 was observed. CONCLUSION: No
      evidence was found for a strong association of TCRAV genes and RA in a white
      population. However, these results suggest a weak association of V5S1*01/*01 with
      DR4 positive RA, although this requires confirmation using larger groups of
      patients and controls.

PMID- 9536825
TI  - Microvascular involvement in systemic sclerosis: laser Doppler evaluation of
      reactivity to acetylcholine and sodium nitroprusside by iontophoresis.
AB  - OBJECTIVES: To investigate the skin vasodilatory response to iontophoretically
      applied acetylcholine (Ach), an endothelium dependent vasodilator, and to sodium
      nitroprusside (SNP), an endothelium independent vasodilator, in patients with
      systemic sclerosis (SSc). METHODS: Eleven SSc patients were preliminarily studied
      (10 females, mean age 40.5; mean disease duration 6.5 years), and 16 age and sex
      matched control subjects. By means of laser Doppler flowmetry skin blood flow was
      evaluated at third finger, at baseline, and after postischaemic hyperaemia test
      and during iontophoretically transcutaneous application of 1% solution of Ach and
      SNP. RESULTS: No significant differences in basal skin blood flow were detected
      between SSc patients and controls. Cutaneous vasodilatory response to ischaemia,
      Ach, and SNP was significantly less pronounced in SSc patients compared with
      controls (p < 0.001). Moreover, among SSc patients a lower (p < 0.05)
      vasodilatory response to Ach compared with ischaemia and SNP was recorded.
      CONCLUSIONS: These data confirm a reduction of skin digital vasodilatory reserve
      in SSc patients and suggest a defect of both endothelial dependent arteriolar
      relaxation and wall compliance in the pathogenesis of this dysfunction.

PMID- 9536827
TI  - Reactive arthritis and ruptured Achilles tendon.

PMID- 9536826
TI  - Basic calcium phosphate crystals induce synthesis and secretion of 92 kDa
      gelatinase (gelatinase B/matrix metalloprotease 9) in human fibroblasts.
AB  - OBJECTIVE: Synovial fluid basic calcium phosphate (BCP) crystals are associated
      with severe joint degeneration accompanied by synovial hypertrophy. The
      metalloprotease 92 kDa gelatinase (MMP-9) has been implicated in the degradation
      of extracellular matrix in osteoarthritis, but the ability of BCP crystals to
      induce gelatinase in human fibroblasts or in adult porcine chondrocytes has not
      previously been studied. The hypothesis that the mitogenic response to BCP
      crystals is accompanied by induction and secretion of MMP-9 was studied. METHODS:
      MMP-9 messenger RNA (mRNA) was detected by northern blot and reverse
      transcription-polymerase chain reaction (RT-PCR). Gelatinase secretion was
      identified by western blot and zymography of conditioned media. RESULTS: BCP
      crystals caused a concentration dependent induction of MMP-9 mRNA accumulation
      and protein secretion in human fibroblasts but not in adult porcine chondrocytes.
      CONCLUSION: BCP crystals induce MMP-9 production by HF but not adult porcine
      chondrocytes. Fibroblast MMP-9 may be an important mediator of the joint
      destruction associated with synovial fluid BCP crystals.

PMID- 9536828
TI  - Dactylitis also involving the synovial sheaths in the palm of the hand: two more
      cases studied by magnetic resonance imaging.

PMID- 9536829
TI  - Pain in the rheumatic diseases.

PMID- 9536830
TI  - What about IgA rheumatoid factor in rheumatoid arthritis?

PMID- 9536831
TI  - High frequency ventilation and respiratory distress syndrome: do we have an
      answer?

PMID- 9536832
TI  - Nebulisation of surfactants in an animal model of neonatal respiratory distress.
AB  - AIMS: To evaluate pulmonary deposition and gas exchange following nebulisation of
      two surfactants by either a jet or an ultrasonic nebuliser. METHOD: After
      bronchoalveolar lavage (BAL), 19 rabbits were ventilated in four groups. Group A1
      (n = 5) and A2 (n = 6) received Technetium-99m labelled Exosurf, and groups B1 (n
      = 4) and B2 (n = 4) received radiolabelled Survanta. Groups A1 and B1 received
      jet nebuliser therapy, whereas groups A2 and B2 received ultrasonic nebuliser.
      Pulmonary deposition, distribution, and blood gases were determined. RESULTS:
      Pulmonary deposition as per cent of initial dose and mg lipid) was 0.28(0.10)% or
      0.59(0.21) mg in group A1, 1.05(0.23)% or 2.21(0.48) mg in group A2, 0.08(0.02)%
      or 0.30(0.08) mg in group B1, and 0.09(0.02)% or 0.34(0.08) mg in group B2.
      Deposition in group A2 was greater than in other groups (p = 0.001). Group A2
      showed a small improvement in blood gases. CONCLUSIONS: Even the highest
      deposition--ultrasonic nebuliser with Exosurf--achieved limited clinical effect.
      The aerosol route is currently not effective for surfactant treatment.

PMID- 9536833
TI  - Randomised trial of erythromycin on the development of chronic lung disease in
      preterm infants.
AB  - AIMS: To determine if erythromycin given from birth reduces the inflammatory
      response and the incidence and severity of chronic lung disease. METHODS: Seventy
      five infants less than 30 weeks of gestation and ventilated from birth for lung
      disease were randomly assigned to receive erythromycin intravenously for 7 days
      or to no treatment. Ureaplasma urealyticum was detected in tracheal secretions by
      culture and polymerase chain reaction. Differential cell counts were obtained
      from bronchoalveolar lavage fluid collected daily for 5 days and concentrations
      of the cytokines interleukins IL-1 beta and IL-8, and tumour necrosis factor
      alpha (TNF-alpha) were measured. Chronic lung disease (CLD) was defined as oxygen
      dependency at 36 weeks of gestation. RESULTS: Nine infants (13%) were positive
      for U urealyticum. The inflammatory cytokines in the lungs increased over the
      first 5 days of life in all babies, but no association was found between their
      concentrations and the development of CLD. Those treated with erythromycin showed
      no significant differences from the non-treated group in the differential cell
      counts or concentrations of the cytokines. The two groups had a similar incidence
      of CLD. Babies infected with U urealyticum did not have a more pronounced
      cytokine response than those without infection. Chorioamnionitis was associated
      with significantly higher concentrations of IL-1 beta and IL-8 on admission:
      these babies had less severe acute lung disease and developed significantly less
      CLD. CONCLUSIONS: U urealyticum in the trachea was not associated with an
      increased inflammatory response in preterm infants. Erythromycin did not reduce
      the incidence or severity of CLD.

PMID- 9536834
TI  - Randomised controlled trial of respiratory system compliance measurements in
      mechanically ventilated neonates.
AB  - AIM: To determine whether outcomes of neonatal mechanical ventilation could be
      improved by regular pulmonary function testing. METHODS: Two hundred and forty
      five neonates, without immediately life threatening congenital malformations,
      were mechanically ventilated in the newborn period. Infants were randomly
      allocated to conventional clinical management (control group) or conventional
      management supplemented by regular measurements of static respiratory system
      compliance, using the single breath technique, with standardised management
      advice based on the results. RESULTS: Fifty five (45%) infants in each group
      experienced one or more adverse outcomes. The median (quartile) durations of
      ventilation and oxygen supplementation were 5 (2-12) and 6 (2-34) days for the
      control group, and 4 (2-9) and 6 (3-36) days for the experimental group (not
      significant). On post-hoc secondary analysis, control group survivors were
      ventilated for 1269 days with a median (quartile) of 5 (2-13) days, and
      experimental group survivors were ventilated for 775 days with a median
      (quartile) duration of 3 (2-8) days (p = 0.03). CONCLUSIONS: Although primary
      analysis did not show any substantial benefit associated with regular measurement
      of static respiratory system compliance, this may reflect a type II error, and a
      moderate benefit has not been excluded. Larger studies are required to establish
      the value of on-line monitoring techniques now available with neonatal
      ventilators.

PMID- 9536835
TI  - Pulmonary artery pressure: early predictor of chronic lung disease in preterm
      infants.
AB  - AIM: To determine if pulmonary artery pressure (PAP) in ventilated preterm
      infants is independently associated with the development of chronic lung disease
      (CLD) and whether early assessment has any prognostic value. METHODS: Two cohorts
      (development n = 55; and validation n = 28) of preterm infants were studied at 24
      hours of age. PAP was assessed non-invasively using its inverse correlation with
      the corrected acceleration time to right ventricular ejection time ratio
      (AT:RVET(c)), calculated from the pulmonary artery Doppler waveform. Clinical and
      respiratory variables were also collected. Using logistic regression analysis to
      identify factors independently associated with CLD, a prognostic score was
      developed to predict CLD. The ability of the score to predict CLD was described
      using receiver operating characteristic (ROC) curves. RESULTS: Birthweight,
      inspired oxygen concentration, and AT:RVET(c) were independently predictive of
      CLD. The area under the ROC curve was 0.96 for the development and 0.89 for the
      validation cohort. Exclusion of AT:RVET(c) resulted in a reduction to 0.88 and
      0.73, respectively. CONCLUSION: PAP is independently associated with CLD. An
      early assessment of PAP using AT:RVET(c) may permit the early prediction of CLD
      as part of a multifactorial scoring system.

PMID- 9536836
TI  - Influence of ethnic origin on respiratory distress syndrome in very premature
      infants.
AB  - AIM: To determine whether the incidence of respiratory distress syndrome (RDS) is
      related to ethnic origin in very premature infants (< or = 32 weeks of
      gestational age and birthweight < or = 2.0 kg). METHOD: A retrospective cohort
      study was performed to determine the incidence of respiratory disorders in
      African, Caribbean, and caucasian infants. An African infant was matched with two
      infants (one of Caribbean and one of caucasian descent) for gestational age and
      birth order and, if several eligible matching infants were found, for gender and
      approximate birth date. Fifty African infants (median gestational age 28 weeks,
      range 23-32) were matched with an infant of Caribbean and one of caucasian
      descent. RESULTS: Compared with the incidence of RDS in African infants (40%),
      that in caucasian infants (75%) was significantly higher (p < 0.05), while the
      incidence in the Caribbean infants (54%) did not differ significantly. Regression
      analysis showed that ethnic origin was related to the occurrence of RDS
      independent of gestational age, size for dates, antenatal steroids, hypertension
      during pregnancy, premature rupture of membranes, maternal smoking, mode of
      delivery and infant gender. CONCLUSION: The enhanced lung maturation found in
      certain ethnic groups, even when born prematurely, has implications for clinical
      management.

PMID- 9536837
TI  - Deformation of the palate in preterm infants.
AB  - AIM: To investigate the effect of gestation, postmenstrual age, and orotracheal
      intubation on palate morphology. METHODS: A prospective study was made of 76
      newborn infants of 25 to 41 weeks' gestation. Palate dimensions were measured on
      plaster models produced from serial palatal impressions. Palate size relative to
      that of the mouth was assessed using a ratio of palate depth to palate width
      (Palatal Index). RESULTS: Palate depth and width were related to postmenstrual
      age and gestation. Palatal Index ranged from 0.15 to 0.57, indicating a wide
      variation in palate shape, but gestation and postmenstrual age had no effect.
      Prolonged intubation had a small effect, equivalent to an increase in palatal
      depth of less than 2 mm at 32 weeks' postmenstrual age. The effect was transient.
      CONCLUSION: Prolonged orotracheal intubation (> 10 days) leads to a small and
      temporary increase in palatal depth. However, this is unlikely to account for
      palatal grooving, which is probably caused by an overgrowth of the lateral
      palatine ridges.

PMID- 9536838
TI  - Cerebral blood flow increases over the first three days of life in extremely
      preterm neonates.
AB  - AIM: To measure changes in cerebral haemodynamics over the first three days of
      life in very preterm infants with normal brains. METHODS: Eleven mechanically
      ventilated infants (median gestational age 26 weeks) without evidence of major
      abnormalities on cranial ultrasound examination were studied. Cerebral blood flow
      (CBF) and cerebral blood volume (CBV) were measured using near infrared
      spectroscopy at least twice over the first three days of life. RESULTS: Cerebral
      blood flow increased significantly with time (p = 0.02; stepwise linear
      regression) and this was independent of mean arterial blood pressure, PaCO2, and
      haematocrit. CONCLUSION: This change is likely to represent a normal adaptive
      response of the cerebral circulation to postnatal life.

PMID- 9536839
TI  - Does positive pressure ventilation increase arginine vasopressin in preterm
      neonates?
AB  - AIM: To examine the effect of intermittent positive pressure ventilation (IPPV)
      on plasma arginine vasopressin concentration (pAVP) in preterm neonates. METHODS:
      Thirty five neonates were classified, at the time of blood sampling, into three
      groups: unstable ventilated; stable ventilated; and stable non-ventilated. A
      modification of an extraction method for pAVP was developed for use in studies on
      very small babies, and sampling methods were compared. RESULTS: The pAVP (median,
      range) was similar in the ventilated (1.85 pmol/l, 0.5 to 3.4) and non-ventilated
      (2.0, 0.5 to 2.6) stable babies, but was significantly higher (5.7, 1.1 to 25) in
      the unstable group. There was an inverse correlation between systolic blood
      pressure and pAVP concentration. CONCLUSIONS: This study shows that in preterm
      neonates pAVP concentration is affected by the clinical condition and blood
      pressure, but not by treatment with IPPV.

PMID- 9536840
TI  - Central-peripheral temperature difference, blood pressure, and arginine
      vasopressin in preterm neonates undergoing volume expansion.
AB  - AIM: To examine the effect of intravascular volume expansion for the treatment of
      hypovolaemia in sick preterm neonates. METHODS: An intravenous infusion of 20 ml
      per kg of 4.5% albumin was given to 14 preterm neonates. The effects on systolic
      blood pressure, central peripheral temperature difference (c-pT), and plasma
      arginine vasopressin concentration (pAVP) were measured. RESULTS: Thirteen babies
      showed a rise in systolic blood pressure. The six babies with the highest initial
      values of pAVP and c-pT showed a fall in both of these after infusion. The babies
      with lower initial pAVP (below 4 pmol/l) showed either a rise (two) or no change
      (six) after albumin infusion. There was a significant correlation between c-pT
      and log pAVP before (r2 = 0.61; p < 0.05) and after infusion (r2 = 0.45; p <
      0.05). CONCLUSIONS: Plasma AVP concentration is related to c-pT in unwell preterm
      newborns. This study suggests that clinical assessment of hypovolaemia in preterm
      newborns is poor and could be improved by using c-pT.

PMID- 9536841
TI  - Impaired phagocytosis and opsonisation towards group B streptococci in preterm
      neonates.
AB  - AIMS: To study the chemiluminescence response in polymorphonuclear leucocytes
      (PMNL) at different stages of maturity and the opsonic capacity of sera with
      defined titres of anti-capsular type III antibodies, after exposure to serotype
      III group B streptococci (GBS). The influence of GBS type III capsule expression
      on PMNL chemiluminescence response was also investigated. METHODS: Two clinical
      isolates of serotype III GBS and two serotype III reference strains which form
      isogenic variants with high and low amounts of capsule substance, respectively,
      were used. PMNL and sera were obtained from adult healthy blood donors, full term
      neonates, and preterm neonates. RESULTS: PMNL from premature infants showed a
      significantly lower chemiluminescence response (p < 0.0001) than the PMNL from
      adults and neonates, while the chemiluminescence response with adult, neonatal,
      and preterm sera gradually diminished. In the presence of a serum pool with a
      standardised complement value, raised (> 10 mg/l), rather than low (< 1.0 mg/l)
      anti-III antibody titres induced a higher chemiluminescence response to the
      capsule expressing variant. When GBS were cultured at pH 5.0, the bacteria had a
      higher buoyant density, reflecting decreased expression of capsule substance
      compared with bacteria grown at pH 7.4. Concomitantly, there was a substantial
      increase in chemiluminescence response for all isolates cultured at the lower pH,
      except for the capsule deficient mutant. CONCLUSIONS: PMNL function and opsonic
      capacity are significantly impaired in neonates and correlate with maturation of
      the newborn child. The combined defect in cellular and humoral defences in
      preterm neonates may contribute to their increased susceptibility to GBS
      infection. Growth conditions for GBS, simulating different in vivo environments,
      greatly affect capsule expression and resistance to phagocytosis.

PMID- 9536842
TI  - Antenatal onset of haemorrhagic and/or ischaemic lesions in preterm infants:
      prevalence and associated obstetric variables.
AB  - AIM: To assess the prevalence of an antenatal onset of haemorrhagic and/or
      ischaemic lesions in preterm infants; to identify possibly related obstetric risk
      factors. METHODS: A prospective cohort study was made of 1332 infants born at
      less than 34 completed weeks, using cranial ultrasound, for the presence of
      antenatal brain lesions (group A) involving the periventricular white matter
      (PVWM) or central grey matter. Entry criteria were presence of (i) cysts in the
      PVWM < 7 days; (ii) increased PVWM echogenicity < 6 hours, confirmed to be white
      matter necrosis at post mortem examination; (iii) a unilateral porencephalic cyst
      < 3 days; (iv) an intraventricular haemorrhage with unilateral parenchymal
      involvement < 6 hours; and (v) symmetrical areas of increased echogenicity in the
      thalami, confirmed to be areas of calcification on post mortem examination. Group
      B consisted of infants with a normal early neonatal ultrasound scan with
      subsequent development of the lesions mentioned above. RESULTS: Twenty four cases
      met the entry criteria for group A: 17 died and five of the seven survivors
      developed cerebral palsy at follow up. Of the whole cohort, 156 (11.7%) infants
      died and in 63 (40.3%) of these a large ultrasound lesion was present. In 17
      (26.9%) cases this lesion was considered to be of antenatal onset. Sixty eight of
      the 1176 (5.8%) survivors developed cerebral palsy and this was attributed to
      antenatal onset in five (7.3%). A comparison of the obstetric risk factors
      between the infants in group A and B, who either died or developed cerebral
      palsy, showed a significant difference in gestational age between the two groups
      (30.9 vs 28.9 weeks; p < 0.001). Prolonged rupture of membranes was significantly
      more common in group B (p = 0.03), while an ominous cardiotachogram was
      significantly more common in group A (p = 0.01), and this remained significant
      following logistic regression analysis. CONCLUSIONS: Although these data suggest
      that most preterm infants did not develop their brain lesions in utero, an
      antenatal onset was not uncommon, especially in those with PVWM lesions, who did
      not survive the neonatal period.

PMID- 9536843
TI  - Antibodies to varicella zoster virus in the cerebrospinal fluid of neonates with
      seizures.
AB  - Four neonates with convulsions had IgG antibodies in their cerebrospinal fluid
      (CSF) to varicella zoster virus (VZV). These antibodies were found in the sera of
      two of these patients after the age of 6 months. Antibodies to 16 different
      microbes were studied from the serum and CSF of 201 neonates with neurological
      problems. The presence of DNA specific to HSV-1, HSV-2, and VZV in the CSF was
      also investigated using the polymerase chain reaction (PCR). Antibodies to VZV
      were detected in the CSF of four neonates. Antibody indices suggested production
      of VZV specific antibodies in the central nervous system. These findings suggest
      that intrathecal production of antibodies to VZV can appear in neonates with
      neurological problems, which suggests that intrauterine VZV infection can be
      acquired without cutaneous symptoms in the mother.

PMID- 9536844
TI  - Consequences for fetus and neonate of maternal red cell allo-immunisation.
AB  - AIMS: To study the distribution of clinically important red cell antibodies in
      pregnancy, and the associated fetal and neonatal morbidity and mortality.
      METHODS: The case notes of women with clinically important red cell antibodies
      identified in their serum during pregnancy were reviewed. RESULTS: During a 12
      month period 22,264 women were referred for antenatal screening. Clinically
      important red cell antibodies were detected in 244 (1%). Of these, 100 were anti
      D and 144 were non-RhD antibodies. There were three intrauterine deaths, three
      fetuses required intrauterine transfusion, 10 neonates were transfused, 27 others
      had phototherapy, and 27 with a positive direct antiglobulin test received no
      treatment. Early fetal losses occurred in the presence of both high and low
      levels of anti-D. CONCLUSIONS: Anti-D remains the most common clinically
      important antibody in pregnancy, and accounts for the greatest fetal and neonatal
      morbidity and mortality. Of the other antibodies detected, anti-c was associated
      with most neonatal morbidity. The production of many of the non-D antibodies
      detected could be avoided by the use of selected red cells when transfusing pre
      menopausal women.

PMID- 9536845
TI  - In vitro effect of dexamethasone phosphate on hematopoietic progenitor cells in
      preterm infants.
AB  - The in vitro effect of dexamethasone on the clonal growth of haematopoietic
      progenitors in preterm infants was investigated. Concentrations of 10(6)M to
      10(9)M were associated with a dose dependent inhibition of colony formation, with
      the most clinically important effects seen on the earliest erythroid and
      granulocyte-macrophage colonies. Because of the potential clinical implications
      of these observations, studies are needed to determine the effects of
      dexamethasone on haematopoiesis in preterm infants.

PMID- 9536846
TI  - Neonatal seizures.

PMID- 9536847
TI  - Thomas Malthus (1766-1834): population growth and birth control.

PMID- 9536848
TI  - Neonatal symptomatic thromboembolism in Germany.

PMID- 9536849
TI  - High serum immunoreactive trypsin not caused by cystic fibrosis.

PMID- 9536850
TI  - Effects of bolus tube feeding on cerebral blood flow velocity in neonates.

PMID- 9536851
TI  - Measures of visual function in minimum datasets.

PMID- 9536852
TI  - Lactate and anion gap in asphyxiated neonates.

PMID- 9536853
TI  - Is ibuprofen a useful treatment for patent ductus arteriosus?

PMID- 9536854
TI  - Gene-nutrient interactions: an important area for consideration.

PMID- 9536855
TI  - Utilization of lipids during exercise in human subjects: metabolic and dietary
      constraints.
AB  - During endurance exercise, skeletal muscle relies mainly on both carbohydrate
      (CHO) and fat oxidation to cover energy needs. Numerous scientific studies have
      shown that increasing the exercise intensity leads to a progressive utilization
      of CHO. The latter will induce a state of glycogen depletion which is generally
      recognized as being a limiting factor for the continuation of strenuous exercise.
      Different dietary interventions have been proposed to overcome this limitation. A
      high-CHO diet during periods of intense training and competition, as well as CHO
      intake during exercise, are known to maintain a high rate of CHO oxidation and to
      delay fatigue. However, it has been recognized also that enhancing fatty acid
      (FA) oxidation during exercise induces a reduced rate of glycogen degradation,
      resulting in an improved endurance capacity. This is most strikingly observed as
      a result of frequent endurance exercise which improves a number of factors known
      to govern the FA flux and the oxidative capacity of skeletal muscle. Such factors
      are: (1) blood flow and capillarization; (2) lipolysis of triacylglycerol (TAG)
      in adipose tissue and circulating TAG and transport of FA from blood plasma to
      the sarcoplasm; (3) availability and rate of hydrolysis of intramuscular TAG; (4)
      activation of the FA and transport across the mitochondrial membrane; (5) the
      activity of enzymes in the oxidative pathway; (6) hormonal adaptations, i.e.
      sensitivity to catecholamines and insulin. The observation that the plasma FA
      concentration is an important factor in determining the rate of FA oxidation, and
      that some dietary factors may influence the rate of FA supply to muscle as well
      as to the mitochondria, has led to a number of dietary interventions with the
      ultimate goal to enhance FA oxidation and endurance performance. It appears that
      experimental data are not equivocal that dietary interventions, such as a high
      fat diet, medium-chain TAG-fat emulsions and caffeine intake during exercise, as
      well as L-carnitine supplementation, do significantly enhance FA oxidation during
      exercise. So far, only regular endurance exercise can be classified as successful
      in achieving adaptations which enhance FA mobilization and oxidation.

PMID- 9536856
TI  - Free amino acids in milks of human subjects, other primates and non-primates.
AB  - Preterm and term transitional milks of human subjects and mature milks of human
      subjects, non-human primates and non-primates were analysed for free amino acids
      (AA) using precolumn phenylisothiocyanate derivatization and liquid
      chromatography. Differences in free AA between three types of human milk were
      small. Milks of pinnipeds (seals and sea lions) contained the highest levels of
      total free AA (8634-20,862 mumol/l), while the milks of cows and sheep had the
      lowest levels of total free AA (1061-1357 mumol/l). The milks of human subjects,
      chimpanzees (Pan troglodytes), gorillas (Gorilla gorilla), elephants (Elephas
      maximus), horses and pigs had intermediate levels of total free AA (3069-7381
      mumol/l). Glutamic acid was the most abundant free AA in milks of human subjects
      (1339-2157 mumol/l), non-human primates (423-2528 mumol/l), elephants (1332
      mumol/l), horses (1119 mumol/l), and cows (349 mumol/l). Taurine was the most
      abundant free AA in milks of pinnipeds (5776-13,643 mumol/l), pigs (1238
      mumol/l), goats (1150 mumol/l) and sheep (341 mumol/l). Taurine was the second
      most abundant free AA in milks of human subjects and non-human primates, while
      histidine was the second most abundant free AA in milks of pinnipeds. Milks of
      each species had a distinctive free AA pattern which may reflect the relative
      importance of the free AA during early postnatal development.

PMID- 9536857
TI  - Apolipoprotein E genotype modulates the effect of black tea drinking on blood
      lipids and blood coagulation factors: a pilot study.
AB  - Apolipoprotein E (ApoE) genotype was determined in sixty-five subjects who had
      taken part in a 4-week randomized crossover trial to compare the effect of six
      mugs of black tea per day v. placebo on blood lipids and blood coagulation
      factors. Four ApoE genotype variants (seven E2/E3, forty-five E3/E3, twelve E3/E4
      and one E4/E4) were found. ApoE allele frequency was within the range typical for
      Caucasian populations (ApoE-E2 5.4%; ApoE-E3 83.8%; ApoE-E4 10.8%). Individuals
      bearing at least one E4 allele had substantially higher levels of serum total
      cholesterol, LDL cholesterol and triacylglycerols. Mean plasminogen activator
      inhibitor (PAI-1) activity was higher in ApoE-E4 allele-bearing individuals
      (E3/E4 + E4/E4, 11.89 (SE 1.27) U/ml; E3/E3, 9.19 (SE 0.80) U/ml; E2/E3, 7.21 (SE
      1.04) U/ml, P values of E4-group v. E3 and E2 being respectively 0.093 and
      0.030). These unexpected findings imply that elevated PAI-1 activity may be a
      hitherto unrecognized additional factor involved in the increased cardiovascular
      disease risk associated with apoE-E4 allele. The interactions between tea
      drinking and genotype were also examined. In the E3/E3 homozygotes, HDL
      cholesterol was significantly reduced in the tea period (mean placebo 1.54 mmol/l
      v. mean tea 1.50 mmol/l, P = 0.027). In the E2/E3 group, triacylglycerol
      concentration was significantly reduced (mean placebo 1.18 mmol/l v. mean tea
      1.09 mmol/l, P = 0.039). Tea also caused a significant decrease of PAI-1 activity
      in the subjects with E2/E3 genotype (mean placebo 7.21 U/ml v. mean tea 5.88
      U/ml, P = 0.007). In the other two genotype groups, there was no significant
      effect of tea. The results indicate that tea drinking has a beneficial effect on
      some cardiovascular disease risk-associated factors, especially in E2 allele
      bearing individuals. Dietary intervention may be particularly effective in
      population groups with certain genetic characteristics.

PMID- 9536858
TI  - The effect of triacylglycerol-fatty acid positional distribution on postprandial
      metabolism in subcutaneous adipose tissue.
AB  - We hypothesized that fatty acids at the sn-2 position of chylomicron
      triacylglycerol are preferentially released into the venous plasma (rather than
      being taken up and stored in the adipocytes) after hydrolysis by lipoprotein
      lipase (EC 3.1.1.34) in adipose tissue. Arteriovenous differences across adipose
      tissue were studied in eight healthy subjects on two occasions for 6 h after
      ingestion of different structured triacylglycerols rich in palmitic acid either
      at the sn-2 or the sn-1,3 positions. In particular the specific fatty acids
      making up lipoprotein fractions and plasma non-esterified fatty acids were
      analysed. After the different meals there were no differences between either
      postprandial arterialized or venous plasma metabolite concentrations. Chylomicron
      triacylglycerol extraction in adipose tissue was the same following the two types
      of fat. There was no difference between the specific fatty acid composition of
      the postprandial non-esterified fatty acid release from adipose tissue after
      ingestion of the two triacylglycerols, indicating that there was no preferential
      release of a saturated fatty acid at the sn-2 position.

PMID- 9536859
TI  - Intestinal absorption of beta-carotene, lycopene and lutein in men and women
      following a standard meal: response curves in the triacylglycerol-rich
      lipoprotein fraction.
AB  - A high intake of fruit and vegetables is believed to be protective against heart
      disease and cancer. beta-Carotene has been closely examined for evidence of these
      protective properties but evidence is still conflicting and there are many other
      carotenoids in plant foods which deserve attention. This paper reports studies on
      the concentrations of lutein and lycopene in the triacylglycerol-rich lipoprotein
      (TRL) fraction of plasma in comparison with beta-carotene following a large dose
      of the respective carotenoids fed with a standard meal after an overnight fast.
      beta-Carotene (40 mg) was given to twelve volunteers (six men and six women) and
      six of the same volunteers (three men and three women) also received 31.2 mg
      lutein or 38 mg lycopene. Plasma was collected at hourly intervals for 8 h and
      the TRL fraction was separated and subsequently analysed for the respective
      carotenoids and retinyl palmitate in the case of beta-carotene. Intestinal uptake
      of the three carotenoids was estimated using the 'area under the curve' method
      and apparent absorption was calculated from these results. The response curves in
      the TRL fraction for beta-carotene and retinyl palmitate occurred maximally over
      the fourth to fifth hour postprandially. There was a correlation between the TRL
      concentrations of beta-carotene and retinyl palmitate (males r 0.62, P < 0.001;
      females r 0.52, P < 0.001) and there was no significant difference between men
      and women either in the total amount of beta-carotene appearing in the TRL
      fraction or in the amount converted to retinol. On estimation, approximately 1.4
      mg of the 40 mg beta-carotene dose was absorbed and this was not significantly
      different from the amount of lycopene (1.0 mg) but significantly different (P <
      0.05) from the amount of lutein (0.8 mg) absorbed, after correction for the
      smaller doses administered. There was approximately a twofold difference between
      subjects in the uptake of beta-carotene into the TRL fraction, a two- to
      threefold variation in lycopene and a two- to threefold variation in lutein.
      Despite these inter-subject differences, in three volunteers between whom there
      was a threefold difference in beta-carotene in the TRL fraction and a twofold
      difference in retinol formation, repeat experiments with beta-carotene 4 months
      later found differences of only 3-6% in the TRL beta-carotene content and 4-9%
      for the TRL retinol formed. In conclusion, large inter-subject variation in TRL
      carotene uptake precluded any differences between sexes but surprising intra
      subject consistency was observed in TRL beta-carotene uptake of three subjects.

PMID- 9536860
TI  - Enzyme activities of rumen particles and feed samples incubated in situ with
      differing types of cloth.
AB  - Three ruminally cannulated non-lactating dairy cows were used to investigate the
      effects of six different bag cloth types with pore size (microns): free surface
      area (%) ratios of 200:45, 41:33, 16:5, 10:2, 6:5 and 1:2 respectively on the
      disappearance of grass silage DM and neutral-detergent fibre (NDF), and on
      particle-associated carboxymethylcellulase (EC 3.2.1.4; CMCase) and xylanase (EC
      3.2.1.8) activities extracted from feed residues. Another objective was to
      compare microbial activity inside the bags and in rumen ingesta. Rumen incubation
      periods were 3, 6, 12, 24, 48 and 96 h. DM and NDF disappearance and particle
      associated enzyme activities were greatly reduced with the smaller pore size
      and/or open surface area. Re-analysing some of the data as a 2 x 2 factorial
      (pore size x free surface area) indicated that, generally, free surface area
      rather than pore size affected the disappearance of feed components and particle
      associated enzyme activities. Enzyme activities were highly correlated with NDF
      disappearance at 6-48 h of incubation. Cumulative area under CMCase and xylanase
      activity curves explained 0.79 and 0.88 of the variation in NDF disappearance
      when different cloth type and 6-48 h incubation data were combined. Weighted mean
      enzyme activities inside the bags were less than 0.35 those in rumen ingesta. The
      highest activity values inside the bags (24 or 48 h) were less than 0.50 those
      found in rumen ingesta. The lower microbial activity inside the bags explains the
      slower rates of NDF digestion reported with in situ techniques than with rumen
      evacuation techniques. The general assumption of similar microbial activity
      inside the bags and in rumen ingesta is not justified by the present results, and
      caution must be taken in interpreting in situ results quantitatively for feed
      evaluation systems.

PMID- 9536861
TI  - Prediction of the chemical composition of lamb carcasses from multi-frequency
      impedance data.
AB  - Multi-frequency bioimpedance analysis (MFBIA) was used to determine the
      impedance, reactance and resistance of 103 lamb carcasses (17.1-34.2 kg)
      immediately after slaughter and evisceration. Carcasses were halved, frozen and
      one half subsequently homogenized and analysed for water, crude protein and fat
      content. Three measures of carcass length were obtained. Diagonal length between
      the electrodes (right side biceps femoris to left side of neck) explained a
      greater proportion of the variance in water mass than did estimates of spinal
      length and was selected for use in the index L2/Z to predict the mass of chemical
      components in the carcass. Use of impedance (Z) measured at the characteristic
      frequency (Zc) instead of 50 kHz (Z50) did not improve the power of the model to
      predict the mass of water, protein or fat in the carcass. While L2/Z50 explained
      a significant proportion of variation in the masses of body water (r(2) 0.64),
      protein (r(2) 0.34) and fat (r(2) 0.35), its inclusion in multi-variate indices
      offered small or no increases in predictive capacity when hot carcass weight
      (HCW) and a measure of rib fat-depth (GR) were present in the model. Optimized
      equations were able to account for 65-90% of the variance observed in the weight
      of chemical components in the carcass. It is concluded that single frequency
      impedance data do not provide better prediction of carcass composition than can
      be obtained from measures of HCW and GR. Indices of intracellular water mass
      derived from impedance at zero frequency and the characteristic frequency
      explained a similar proportion of the variance in carcass protein mass as did the
      index L2/Z50.

PMID- 9536862
TI  - Compensatory nutrition-directed mammary cell proliferation and lactation in rats.
AB  - The proper use of a time-dependent and controlled nutrition regimen during the
      hormone-sensitive growth phase before first parturition can significantly affect
      mammary growth and subsequent lactation performance. The objective of the present
      study was to determine if a compensatory nutrition regimen improves lactation
      performance by affecting proliferation and apoptosis of mammary epithelial cells.
      Forty female rats (7 weeks of age, average weight 148 g) were assigned to either
      (1) control, free access to diet or (2) stair-step compensatory nutrition
      regimen, an alternating 3-4-week schedule beginning with an energy-restricted
      diet (31.2% restriction) for 3 weeks, followed by the control diet for 4 weeks.
      Estimated milk yield was greater (P < 0.05) on day 15 of lactation in the
      compensatory nutrition group than in the control group. Mammary cell
      proliferation values were 1.4- and 2.7-fold greater in mammary tissue from the
      compensatory group during pregnant and early lactating stages respectively,
      compared with those from the control group. Ornithine decarboxylase (EC 4.1.17)
      mRNA was 24% higher (P < 0.05) in mammary tissues of rats from the compensatory
      nutrition group during pregnancy than in those from the control group. These
      results indicate that the compensatory nutrition regimen imposed during the
      peripubertal growth phase stimulated mammary epithelial cell proliferation and
      improved lactation performance.

PMID- 9536863
TI  - Cholesterol lowering in pigs through enhanced bacterial bile salt hydrolase
      activity.
AB  - The effect of feeding live Lactobacillus reuteri cells containing active bile
      salt hydrolase (BSH) on plasma cholesterol levels was studied in pigs. During an
      experiment lasting 13 weeks, twenty pigs were fed on a high-fat, high
      cholesterol, low-fibre for the first 10 weeks, and a regular pig diet for the
      last 3 weeks. One group of animals received, twice daily, 11.25 (SD 0.16) log10
      colony forming units of the potential probiotic bacteria for 4 weeks (from week 3
      until week 7). From week 8 onwards, the treated group was again fed on the same
      diet as the control group without additions. The total faecal Lactobacillus
      counts were only significantly higher in the treated pigs during the first 2
      weeks of L reuteri feeding. Based on limited data, it was suggested that the
      administered Lactobacillus species had caused a temporary shift within the
      indigenous Lactobacillus population rather than permanently colonizing the
      intestinal tract. The probiotic feeding brought about significant lowering (P <
      or = 0.05) of total and LDL-cholesterol concentrations in the treated pigs
      compared with the control pigs, while no change in HDL-cholesterol concentration
      was observed. The data for faecal output of neutral sterols and bile salts were
      highly variable between the animals of each group, yet they indicated an
      increased output in the treated pigs. Although the blood cholesterol levels went
      up in both groups during the 3 weeks following the Lactobacillus administration
      period, significantly lower serum total and LDL-cholesterol levels were observed
      in the treated pigs. During the final 3 weeks of normalization to the regular
      diet, cholesterol concentrations significantly decreased in both animal groups
      and the differences in total and LDL-cholesterol concentrations between the
      groups largely disappeared.

PMID- 9536864
TI  - The effect of different dietary fatty acids on lipoprotein metabolism:
      concentration-dependent effects of diets enriched in oleic, myristic, palmitic
      and stearic acids.
AB  - While it is well established that the fatty acid composition of dietary fat is
      important in determining plasma lipoprotein cholesterol concentrations, the
      effects of changing the absolute quantities of the individual fatty acids are
      less clear. In the present study Golden Syrian hamsters were fed on isoenergetic,
      low cholesterol (0.05 g/kg) diets containing 100, 150 or 200 g added fat/kg. This
      consisted of triolein (TO) alone, or equal proportions of TO and either
      trimyristin (TM), tripalmitin (TP) or tristearin (TS). Each trial also included a
      control group fed on a diet containing 50 g TO/kg. As the mass of TO in the diet
      increased, plasma VLDL-cholesterol concentrations rose. The TM-rich diets
      produced a concentration-dependent increase in total plasma cholesterol which was
      a result of significant increases in both VLDL and HDL levels. The TP-rich diets
      increased plasma LDL- and HDL-cholesterol levels in a concentration-dependent
      manner. TS-containing diets did not increase the cholesterol content of any of
      the major lipoprotein fractions. Hepatic LDL-receptor mRNA concentrations were
      significantly decreased in animals fed on TP, while apolipoprotein B mRNA
      concentrations were significantly increased. Thus, on a low-cholesterol diet,
      increasing the absolute amount of dietary palmitic acid increases LDL-cholesterol
      more than either myristic or stearic acid. These effects on lipoprotein
      metabolism may be exerted through specific modulation of the expression of the
      LDL receptor and apolipoprotein B genes.

PMID- 9536865
TI  - Comparison of short- and long-term effects of different dietary fats on the
      hepatic uptake and metabolism of chylomicron remnants in rats.
AB  - The uptake and metabolism of [14C]oleate-labelled chylomicron remnants derived
      from olive oil, maize oil, palm oil, fish oil or butter fat was investigated
      using perfused livers from rats fed on the corresponding fat-supplemented diet
      (providing 40% of the dietary energy) or a low-fat diet for 21 d. The percentage
      of added [14C]oleate-labelled remnant removed from the perfusate was similar for
      livers from rats fed on the fat-supplemented diets irrespective of the type of
      fat fed, whereas livers from rats fed on the low-fat diet removed more labelled
      fish oil and butter fat remnants than olive, maize or palm oil remnants.
      Following hepatic uptake in the fat-supplemented groups, the oxidation of
      [14C]oleate-labelled remnant lipid from maize oil, fish oil, and butter fat
      remnants was greater than that of the lipids from olive and palm oil remnants,
      although only the oxidation of lipids from maize and palm oil remnants was
      increased by prior fat-supplementation of the diet. In addition, the livers from
      rats fed on the fish-oil-supplemented diet incorporated more [14C]oleate-labelled
      remnant lipid into phospholipid compared with the livers from rats fed on the
      other fat-supplemented diets or the low-fat diets. These investigations show that
      both prior fat feeding and the composition of the fat fed, as well as the fatty
      acid composition of the chylomicron remnant particles themselves, influence the
      uptake and metabolism of chylomicron remnants by the liver.

PMID- 9536866
TI  - Lipid accumulation in obese Zucker rats is reduced by inclusion of raw kidney
      bean (Phaseolus vulgaris) in the diet.
AB  - The effects of inclusion of different levels of raw kidney bean (Phaseolus
      vulgaris) of high lectin content (27 g/kg meal) in a high-quality (lactalbumin)
      control diet were tested in nutritional trials on the growth and metabolism of
      obese Zucker (fafa) rats and their lean littermates in comparison with pair-fed
      controls. All diets contained 100 g total protein/kg and either 50 g lipids/kg
      (low fat) or 150 g lipids/kg (moderate fat). The growth of both obese and lean
      rats on bean diets was retarded by the daily bean intake in a dose-dependent
      manner. However, most of this was because bean-fed rats contained less body fat
      than the controls after 10 d. Thus, after feeding low-fat diets containing up to
      130 g kidney bean/kg (lectin intake < or = 0.2 g/kg body weight (BW) per d) in
      both 10 d and 70 d trials, the bodies of obese rats contained less fat but not
      protein than their pair-fed controls. Moreover, by increasing the lipid content
      of the diet to 150 g/kg, the level of bean inclusion could be increased to 280
      g/kg (lectin intake > or = 0.4 g/kg BW per d) without loss of body protein and
      skeletal muscle. Although these rats contained more body fat than those which
      were fed on low-fat diets, their weight reduction could be accounted for
      exclusively by reduced lipid content. In contrast, significant body protein loss
      occurred when the same diet of high lectin content was fed to lean littermates.
      Plasma insulin levels were significantly depressed in the obese Zucker rats on
      bean diets but the pancreas was not significantly enlarged nor its insulin
      content changed in 10 d trials. However, significant pancreatic growth occurred
      on long-term (70 d) bean feeding compared with pair-fed controls. The results
      suggest that, in addition to animal nutrition, it may also be possible to use the
      bean lectin as a dietary adjunct or therapeutic agent to stimulate gut function
      and ameliorate obesity if a safe and effective dose-range can be established for
      human subjects.

PMID- 9536867
TI  - The impact of low birth weight on the visual pathway.

PMID- 9536868
TI  - Is there a role for computerised image analysis in glaucoma management?

PMID- 9536869
TI  - Striving for the perfect keratoprosthesis.

PMID- 9536870
TI  - Telemedicine and computers in diabetic retinopathy screening.

PMID- 9536871
TI  - How dangerous a world is it?

PMID- 9536872
TI  - The contribution of low birth weight to severe vision loss in a geographically
      defined population.
AB  - AIMS: To describe the birthweight specific rate of severe vision loss among
      babies born between 1 January 1984 and 31 December 1987 to mothers resident in a
      geographically defined area, to classify the causes of vision loss by time of
      origin, and to describe the associated sensory and motor impairments and
      disabilities. METHODS: Cases were identified from a population register of
      children with early childhood impairment, which uses multiple sources of
      ascertainment. Further clinical information was retrieved from hospital records
      and by asking ophthalmologists caring for the children. RESULTS: 166 (1.25/1000
      live births) children with severe vision loss diagnosed by the age of 5 years
      were identified. The rate among babies born weighing less than 1500 g at birth
      was 26 times higher than the rate for babies between 2500 g and 3499 g. These
      very low birthweight babies contribute 17.5% of all severely visually impaired
      children. Almost two thirds of children with severe vision loss have a lesion of
      prenatal origin. Other sensory or motor deficits are present in 69% of the
      children. Retinopathy of prematurity accounted for 5.4% of all visually impaired
      children and seven of the 166 children met the criteria for perinatal asphyxia.
      CONCLUSIONS: Although the contribution made by babies with a low birth weight to
      overall severe vision loss in the community is small, many of these children have
      additional impairments and probably place considerable demands on health and
      educational services and families. Reduction in the frequency of vision problems
      in the preschool population as a whole is unlikely to occur until there are major
      advances in the understanding of the aetiology and prevention of eye conditions
      of genetic, prenatal, and developmental origin.

PMID- 9536873
TI  - Reproducibility of topographic measures of the glaucomatous optic nerve head.
AB  - AIMS/BACKGROUND: Laser scanning tomography provides an assessment of three
      dimensional optic disc topography. For the clinical purpose of follow up of
      glaucoma patients, the repeatability of the various measured variables is
      essential. In the present study, the reproducibility of morphometric variables
      calculated by the topographic scanning system, TopSS (Laser Diagnostic
      Technology, San Diego, CA) was investigated. METHODS: Two independent
      measurements (30 minutes apart) each consisting of three complete images of the
      optic disc were performed on 16 eyes of 16 glaucoma patients using a TopSS. The
      instrument calculates 14 morphometric variables for the characterisation of the
      optic disc. RESULTS: From the two tailed paired tests, all variables were seen to
      have good reproducibility. However, correlation and regression analyses showed
      that only the three variables, volume below, half depth area, and average cup
      depth, are acceptably reproducible. CONCLUSION: The TopSS provides three
      variables which describe the physiological shape of the optic disc that have high
      reproducibility. These three variables might be useful for following the
      progression of optic disc changes in glaucoma patients.

PMID- 9536874
TI  - Clinical results of implantation of the Chirila keratoprosthesis in rabbits.
AB  - AIMS/BACKGROUND: An ideal keratoprosthesis (KPro) would closely resemble a donor
      corneal button in terms of its surgical handling, optics, and capacity to heal
      with host tissue in order to avoid many of the complications associated with the
      KPros which are currently in clinical use. This study was carried out to assess
      the long term clinical outcomes on implantation of the core and skirt poly(2
      hydroxyethyl methacrylate) KPro in animals. METHODS: 20 KPros were made and
      implanted as full thickness corneal replacements into rabbits and followed for up
      to 21 months to date. RESULTS: 80% of the prostheses have been retained, with a
      low incidence of complications such as cataract, glaucoma, and retroprosthetic
      membrane formation which are frequently associated with KPro surgery.
      CONCLUSIONS: KPros of this type may offer promise in the treatment of patients
      for whom penetrating keratoplasty with donor material carries a poor prognosis.
      Refinement of the KPro and further animal trials, including implantation into
      abnormal corneas, are however mandatory before human implantation could be
      planned.

PMID- 9536875
TI  - Natural history of recurrent erosion syndrome--a 4 year review of 117 patients.
AB  - AIMS/BACKGROUND: Recurrent erosion syndrome encompasses a group of mixed
      aetiologies for which there are a number of methods of management which may
      influence the course of the disease. METHODS: The outcomes of a cohort of
      patients initially treated with topical lubricants were studied. 117 consecutive
      patients presenting over 1 year with a history of recurrent erosions were
      enrolled, baseline characteristics were documented, and treatment with lubricants
      was initiated. Patients were surveyed 4 years later inquiring about symptoms and
      treatments required. RESULTS: A total of 94 (80%) of the initial cohort were
      contacted. The mean age was 44 years and the sex distribution was 44 males to 50
      females. The mean period of follow up was 48 months. 55 (59%) were still
      symptomatic with attacks occurring at a median frequency of 60 days. 13 patients
      (24%) complained of an episode at least every week and 28 patients (51%) suffered
      at least every month. The median pain score (analogue scale of 1-10) was 2.5.
      Seventy five per cent (n = 21) of patients with epithelial basement membrane
      dystrophy (EBMD) were symptomatic compared with those with a traumatic aetiology
      among whom 46% (n = 28) were symptomatic. This difference was significant (p =
      0.02). Those with EBMD were more likely to be continuing to use topical
      lubricants than the trauma group. CONCLUSION: Patients with a traumatic aetiology
      are less likely to suffer chronic recurrent erosion syndrome than those with
      EBMD.

PMID- 9536876
TI  - Intrascleral dissemination of infectious scleritis following pterygium excision.
AB  - AIMS: To assess the clinical pictures, possible pathogenesis, management, and
      therapy of patients with infectious scleritis associated with multifocal scleral
      abscesses following pterygium excision. METHODS: The records of patients with
      infectious scleritis after pterygium excision who developed multifocal scleral
      abscesses presenting from 1988 to the end of 1995 were reviewed. Early culture of
      abscesses was performed, and topical, systemic antimicrobials, or both were given
      to all patients. Fourteen eyes were operated on in addition to antimicrobial
      treatment. RESULTS: The initial culture reports of scleral ulcers identified
      Pseudomonas species in 12 of these 18 patients, Aspergillus in one, Mycobacterium
      fortuitum in one, and mixed organisms in four. Subsequent abscess cultures were
      taken from 15 of the infected eyes, and revealed the same organism as the initial
      culture in 12. Associated complications included four serous retinal detachments,
      three choroidal detachments, two double detachments, five complicated cataracts,
      and four recurrences of the initial infection. Four eyes required eventual
      enucleation and 11 eyes regained useful vision. CONCLUSIONS: With subsequent
      abscess cultures proving to be the same organism as found in the initial ulcer,
      the abscess formation appears to represent intrascleral dissemination. Early
      diagnosis and appropriate, prolonged topical plus systemic antimicrobial
      treatment are essential to halt the progression of such severe infections.

PMID- 9536877
TI  - Reliable keratometry with a new hand held surgical keratometer: calibration of
      the keratoscopic astigmatic ruler.
AB  - AIM: Some surgeons consider hand held surgical keratometers unreliable. This may
      be due to incorrect use through not realising that the distance that the
      keratometer is held from the cornea influences the shape of the image. When a
      keratometer is held closer to the astigmatic cornea, the elliptical image will
      appear more circular, particularly for larger degrees of astigmatism. However,
      the keratoscopic astigmatic ruler (KAR) has design features that correct the
      hitherto unrecognised problems with the use of a hand held keratometer. This
      study assesses the reliability and accuracy of measurement of astigmatism using
      the KAR. METHODS: The KAR and the Bausch & Lomb keratometer (B&L) were compared
      using six back surface toric cut contact lens blanks representing 1 to 6 dioptres
      of astigmatism. Two observers (one experienced in the use of the keratometers,
      the other a novice) took eight randomly repeated "masked" measurements of each
      lens blank with the KAR and four measurements with the B&L in a similar fashion.
      RESULTS: There was no difference between the measurements with either instrument
      by each of the observers (p = 0.95, ANOVA). The standard error of measurement for
      the KAR was 0.59 D, for the B&L, 0.31 D. The intraclass correlation coefficient
      of reliability for the KAR was 0.90 and for the B&L it was 0.97. The coefficient
      of repeatability for the KAR was plus or minus 0.83 D, and for the B&L plus or
      minus 0.77 D. The interobserver reliability for the KAR was 0.898, and for the
      B&L, 0.975. CONCLUSION: These results suggest that the KAR has good reliability
      and reproducibility and compares favourably with the B&L keratometer.
      Inexperience with use does not affect reliability.

PMID- 9536878
TI  - Short-term comparative study of topical 2% carteolol with and without
      benzalkonium chloride in healthy volunteers.
AB  - AIM: A crossover, randomised double blind study was undertaken in 30 healthy
      volunteers, in order to compare the tolerance of 2% carteolol with and without
      preservative in short term use. METHODS: Complete ophthalmic examinations were
      performed before and 30, 60, and 180 minutes after instillation of one drop of
      the solution, and after 3 days of preservative treatment. After a 5 day washout,
      the same examinations were done with the second drug. RESULTS: Results showed
      good general tolerance for both formulations. No significant difference in
      subjective tolerance, corneal aesthesiometry, punctuate keratitis, Schirmer's
      test, intraocular pressure (IOP) decrease (about 25% in the two groups at 3
      hours, 10% after 3 days of treatment), resting cardiac frequency, or blood
      pressure was observed. However, break up time was significantly reduced from
      baseline by preserved carteolol both at 3 hours (10.40 (5.9) seconds to 6.15
      (3.9) seconds, p = 0.001) and after 3 days (7.72 (5.5) seconds, p = 0.04).
      Preservative free carteolol did not significantly change the break up time
      (baseline 9.08 (5.7) seconds; 3 hours = 7.88 (5.5) seconds, not significant; day
      3 = 8.35 (5.8), non-significant). CONCLUSIONS: These results confirm that
      carteolol is well tolerated, either with or without preservative. The
      preservative free group showed better stability of the tear film, without loss of
      effect on IOP. This difference, although mild in the healthy young subjects in
      the present study could be much more relevant in those patients treated long
      term, older patients, and/or those suffering from ocular surface disorders. In
      such instances, preservative free drugs could be of potential benefit to protect
      the lacrimal fluid integrity and corneoconjunctival surface.

PMID- 9536879
TI  - Echographic measurements of the retrobulbar optic nerve in normal and
      glaucomatous eyes.
AB  - AIM: A study was designed to investigate whether measurements of the optic nerve
      diameter (OND) and cross sectional area (ONCSA), as measured by B-scan
      ultrasonography, are altered in glaucoma. The reproducibility and test-retest
      variability of echographic estimates of retrobulbar optic nerve dimensions was
      also tested. METHODS: One eye of 49 glaucoma patients and 90 control subjects
      underwent five repeated echographic measurements of the maximal interpial
      diameter and cross sectional area of the orbital optic nerve on two separate
      occasions. All measurements were taken by one experienced ultrasonographer.
      RESULTS: Mean optic nerve diameter (SD) for the control group was 2.86 (0.46) mm,
      and was independent of height (multiple regression analysis: p = 0.21), axial
      length (p = 0.74), spherical equivalent (p = 0.97), sex (ANOVA: p = 0.36), or
      race (p = 0.14), but was inversely related to age (p = 0.01). Reproducibility of
      OND readings in control subjects was 0.149 mm (coefficient of repeatability).
      Test-retest variability of interpial diameter was -0.02 (0.29) mm. Mean interpial
      diameter of the optic nerve was significantly smaller among glaucomatous eyes
      (2.58 (0.501) mm) than controls (Mann-Whitney U test: p < 0.0001). Glaucomatous
      optic nerves also had a significantly smaller cross sectional area (6.68 (2.58)
      mm2) than those of healthy volunteers (8.25 (1.67) mm2) (p = 0.004). CONCLUSION:
      Echographic measurements of the orbital optic nerve are highly reproducible and
      not subject to clinically meaningful test-retest variability. Optic nerve
      interpial diameter and cross sectional area are reduced in glaucomatous eyes,
      reflecting nerve fibre loss. This technique may be useful in distinguishing
      between normal and glaucomatous eyes where optic disc morphometry is inconclusive
      or impossible as a result of opaque media.

PMID- 9536880
TI  - Fluorescein angiographic correlation of focal narrowing of retinal arterioles in
      glaucoma.
AB  - BACKGROUND: Recent studies have shown that focal narrowing of retinal arterioles
      in the parapapillary region occurs in eyes with optic neuropathies such as
      glaucoma. This study evaluated whether these vessel constrictions detected
      ophthalmoscopically have an equivalent in angiographic imaging of the fundus.
      METHODS: Fluorescein angiograms and colour wide angle fundus photographs of 33
      patients with open angle glaucoma and 76 subjects with normal optic nerves were
      examined for focal narrowing of retinal arterioles. The angiograms had primarily
      been taken for other reasons such as age related macula degeneration. RESULTS:
      All focal narrowings of retinal arterioles detected on fundus photographs showed
      a localised constriction of vessel filling in the fluorescein angiograms. Degree
      of vessel narrowing on the fundus photographs and degree of constriction of the
      fluorescein vessel filling were significantly (p < 0.001) correlated with each
      other. CONCLUSIONS: Focal narrowing of retinal arterioles in the parapapillary
      region of eyes with optic neuropathies represents a real stenosis of the vessel
      lumen and is not due to an ophthalmoscopic artefact.

PMID- 9536881
TI  - Does Horner's syndrome in infancy require investigation?
AB  - AIMS: To evaluate whether isolated Horner's syndrome presenting in the first year
      of life warrants investigation. METHODS: Retrospective review of 23 children
      presenting with Horner's syndrome in the first year of life. RESULTS: In 16
      patients (70%) no cause was identified. Birth trauma was the most common
      identifiable cause (four patients). Twenty one children (91%) had urinary
      vanillylmandelic acid (VMA) measured and 13 patients (57%) underwent either
      computed tomography or magnetic resonance imaging of the chest and neck. These
      investigations revealed previously undisclosed pathology in only two--one
      ganglioneuroma of the left pulmonary apex and one cervical neuroblastoma. A
      further patient was known to have abdominal neuroblastoma before presenting with
      Horner's syndrome. There were no cases of Horner's syndrome occurring after
      cardiothoracic surgery. Long term follow up of the patients (mean 9.3 years) has
      not revealed further pathology. CONCLUSIONS: Routine diagnostic imaging of
      isolated Horner's syndrome in infancy is unnecessary. Infants should be examined
      for cervical or abdominal masses and involvement of other cranial nerves. If the
      Horner's syndrome is truly isolated then urinary VMA levels and follow up in
      conjunction with a paediatrician should detect any cases associated with
      neuroblastoma. Further investigation is warranted if the Horner's syndrome is
      acquired or associated with other signs such as increasing heterochromia, a
      cervical mass, or cranial nerve palsies.

PMID- 9536882
TI  - Long-term effect of hypermetropic anisometropia on the visual acuity of treated
      amblyopic eyes.
AB  - AIM: To evaluate the effect of the extent of hypermetropic anisometropia on the
      long term visual acuity results in amblyopic eyes following their treatment by
      occlusion. METHODS: The visual acuity of 86 patients, who had been treated for
      unilateral amblyopia by occlusion of the fellow eye and followed up at least to
      the age of 9 years, was examined 6.4 years, on average, after cessation of
      treatment. Patients were divided into two groups--those with a small amount of
      hypermetropic anisometropia, where the spherical equivalent difference between
      the eyes ranged between 0 and +1.50 dioptres, and those with a large amount of
      hypermetropic anisometropia, where the difference was +1.75 dioptres or greater.
      RESULTS: Deterioration of visual acuity after cessation of occlusion treatment
      occurred in 51% of the patients in the group with a small amount of anisometropia
      and in 75% of the patients in the group with a large amount. At cessation of
      treatment, the average visual acuity in both groups was 20/40+. At the long term
      follow up examination, however, the average visual acuity was 20/40- and 20/70,
      respectively. This difference was statistically significant. CONCLUSIONS:
      Hypermetropic anisometropia greater than 1.50 dioptres appears to be a risk
      factor for deterioration of visual acuity in the long term, following treatment
      of amblyopic eyes by occlusion of the fellow eye.

PMID- 9536883
TI  - Ocular changes associated with Giardia lamblia infection in children.
AB  - BACKGROUND: The protozoan disease giardiasis can cause ocular complications,
      including "salt and pepper" retinal changes. METHODS: Ophthalmic examinations
      were performed in 141 children (mean age 4.7 (SD 2.0) years) with active or past
      giardiasis diagnosed on the basis of microscopic examination of stool specimens
      or duodenal secretions--53 were newly diagnosed and untreated (group A), 50 had
      active infections in spite of metronidazole therapy (group B), and 38 had been
      successfully treated, with negative stool specimens for 1-3 years (group C). 300
      children with no evidence of giardiasis were used as controls. RESULTS: Salt and
      pepper retinal changes (with normal electroretinographic findings) were diagnosed
      in 28 (19.9%) of the patients with giardiasis (11 from group A, 10 from group B,
      and seven from group C), including five pairs of siblings. In all subgroups, the
      children with retinal changes were consistently younger than those with normal
      retinas. In eight cases, the lesions could be visualised only with direct
      ophthalmoscopy. CONCLUSION: Our findings indicate that asymptomatic, non
      progressive retinal lesions are particularly common in younger children with
      giardiasis. This risk does not seem to be related to the severity of the
      infection, its duration, or the use of metronidazole but may reflect a genetic
      predisposition.

PMID- 9536884
TI  - Adjunctive use of mitomycin C on endoscopic lacrimal surgery.
AB  - AIMS: Endoscopic endonasal dacryocystorhinostomy (DCR) has some advantages over
      external DCR as a less invasive method with no skin incisions. But the success
      rate of the operation has not reached the level of external method. In this
      study, a wound healing inhibitor mitomycin C was used intraoperatively to prevent
      the closure of the osteum after the operation. METHODS: Endoscopic endonasal DCR
      was performed on 40 eyes of 39 patients (26 female, 13 male). Mitomycin C was
      applied to the ostium in 14 of 23 patients who had undergone primary endoscopic
      DCR by means of a microdrill and in eight of 17 patients who had a revision
      endoscopic DCR secondary to a previously failed external DCR. RESULTS: The
      postoperative follow up period was 9-27 (mean 18.2) months. The success rate of
      endoscopic DCR with intraoperative mitomycin C was 77.3%, whereas the success
      rate of endoscopic DCR without mitomycin C was 77.8%. The statistical analysis
      did not show a difference between the two groups according to the ostium size and
      their success rates. CONCLUSIONS: Adjunctive use of a wound healing inhibitor is
      considered to increase the success rate of endoscopic endonasal DCR. Its
      intraoperative use seems to be easy and safe. But the study of this limited
      series shows no benefit in using it.

PMID- 9536885
TI  - Dissociated effects of botulinum toxin chemodenervation on ocular deviation and
      saccade dynamics in chronic lateral rectus palsy.
AB  - AIM: Changes in saccade velocity/amplitude characteristics (main sequence) and
      attenuation of distance esotropia in response to botulinum toxin (BTX-A)
      chemodenervation of the antagonist medial rectus were studied in a group of nine
      patients with chronic lateral rectus palsy. METHODS: Serial measurements of
      ocular deviation and infrared oculograms of saccadic eye movements to targets at
      5 degrees-20 degrees of lateral gaze were made before injection and at 2, 4, 8,
      16, and 20 weeks after injection. RESULTS: At 2 weeks after injection, the ocular
      deviation changed by a mean of 34.5 prism dioptres and the 5 degrees and 10
      degrees adduction saccades were significantly slowed (p < 0.02 Wilcoxon signed
      rank test). By the second examination, however, the adducting saccade peak
      velocity had returned to normal while the mean ocular deviation remained
      significantly changed (p = 0.01 Wilcoxon matched pairs). By 20 weeks the mean
      ocular deviation was not significantly different from that before injection (p =
      0.14 matched pairs). CONCLUSIONS: The ocular realignment caused by BTX-A may
      persist after saccadic function has been restored. This may be because toxin may
      have a more profound and long lasting effect on the orbital singly innervated
      fibres which are active tonically at rest to hold gaze whereas there is relative
      sparing of the additional motor units recruited during fast eye movements.

PMID- 9536886
TI  - BD8 certification of visually impaired people.
AB  - BACKGROUND: There is debate as to the completeness of the blind and partial sight
      registers in England and Wales. The purpose of this study was to estimate the
      proportion of eligible visually impaired people attending the hospital eye
      service who have a BD8 certificate and to identify factors associated with not
      being certified. METHODS: Cross sectional survey of patients attending
      outpatients by medical record review analysed by multiple logistic regression.
      RESULTS: 51% (43%, 58%) of patients identified as eligible for registration did
      not have a BD8 certificate. The severity of visual impairment and the main
      diagnosis in terms of requirements for treatment, permanence of visual loss, and
      visual field loss were independently associated with non-certification. A
      partially sighted patient is estimated to be three times more likely to not have
      a BD8 certificate as a blind patient of similar diagnosis (adj OR: 3.4 (95% CI:
      1.7, 6.8)). A patient whose impairment is due to abnormal visual fields is
      estimated to be greater than three times more likely to be non-certified than one
      with low visual acuity of similar severity and cause (adj OR: 3.6 (95% CI: 1.0,
      12.7)). People whose impairment is potentially reversible are estimated to be
      eight times (8.3 (2.2, 31.4)) more likely not to have a certificate compared with
      people who had permanent non-treatable visual loss; and in those with permanent
      visual loss, a requirement for ongoing treatment was found to be associated with
      a lower odds of certification. CONCLUSIONS: These data strongly suggest that
      epidemiological data collected during registration are biased towards permanent,
      non-treatable causes of visual loss and those which affect central rather than
      peripheral vision. Certain subgroups of the visually impaired are likely to be at
      greater risk of non-certification. BD8 guidelines need to be simplified.

PMID- 9536887
TI  - Capillaries in the epithelium of pterygium.
AB  - AIM: To present new morphological observations of intraepithelial capillaries in
      pterygium and to provide some explanations for this phenomenon. METHODS: The
      ultrastructural features of pterygia from 26 patients were examined. Surgically
      excised tissue was processed for conventional light and transmission electron
      microscopy. RESULTS: Individual capillaries within the epithelium of the anterior
      half towards the head of pterygia were identified in 11 specimens out of 26
      pterygia examined (42.3%). The perivascular connective tissue of the
      intraepithelial capillaries contained fibroblasts, collagen fibrils, and elastin
      like material. Epithelial cells surrounding these capillaries showed defects in
      the basal lamina in contrast with the continuous basal lamina of the endothelium.
      In the intercellular space of the epithelium an amorphous substance, occasional
      fibroblast processes, and collagen fibrils were frequently observed. CONCLUSION:
      Capillaries in the epithelium of pterygia are rare, but not exceptional. The
      ingrowth of these vessels from the stroma into the epithelium can be interpreted
      as a reaction to hypoxia or deficiency of any other substance transported via the
      bloodstream. Apparently, the perivascular connective tissue can be used by
      ingrowing fibroblasts as a migration pathway. The migrating fibroblasts appear to
      use the defects of the epithelial basal lamina (whether partially or complete) in
      order to reach the intercellular space. It is possible that collagen fibrils in
      the epithelial intercellular space have been laid down by fibroblasts which
      contribute to the pathological dedifferentiation of the conjunctival epithelium.

PMID- 9536888
TI  - Systemic and local immunological features of atopic dermatitis patients with
      ocular complications.
AB  - AIMS: Clinical factors and data from recent cases of atopic dermatitis (AD) (with
      or without ocular complications) and non-AD cases were examined to evaluate the
      mechanism of atopic ocular complications. METHODS: IgE-RAST for eight allergens
      including rice, egg, and mite and serum total IgE were measured in 216 patients
      with AD (70 ocular type, 146 non-ocular type) and 69 non-AD individuals. Tear
      histamine and leukotriene B4 (LTB4) levels were also measured. RESULTS: The serum
      levels of IgE were significantly increased in AD patients with ocular
      complications compared with those without ocular complications. The positive
      rates of IgE-RAST for rice and wheat were significantly higher in ocular type AD
      than in non-ocular type AD. In ocular type AD, serum IgE was significantly
      increased in patients with cataract compared with that in those without cataract.
      Tear histamine and LTB4 levels in AD patients with ocular complications showed
      significant elevations compared with those in patients with pure AD and controls.
      CONCLUSIONS: These results suggest that ocular type AD belongs to the most severe
      end of the spectrum of AD, and that some food antigens may contribute to the
      pathogenesis of severe AD resulting in ocular complications.

PMID- 9536889
TI  - CA 19-9 ELISA test: a new method for studying mucus changes in tears.
AB  - AIMS: This study investigated mucus changes in the tears in various eye
      conditions using impression cytology. The quantity of mucins was measured by
      enzyme linked immunosorbent assay (ELISA) using the tumour marker CA 19-9. This
      assay quantifies the sialylated Lewis(a) structure mainly associated with ocular
      mucins. METHODS: Impression cytology was performed using a cellulose nitrate
      membrane, on 53 healthy patients, 50 glaucoma patients treated with beta
      blockers, 24 patients suffering from dry eye syndrome, and 45 contact lens
      wearers. The tear film glycoproteins were eluted and CA 19-9 was measured.
      RESULTS: CA 19-9 content expressed as kilo units (kU) per microgram of tears was
      significantly decreased in dry eye syndrome (25.8 kU (SD 17.3)/microgram) (p <
      0.05), glaucoma patients over 60 years (28.9 (19.5) kU/microgram) (p < 0.05), and
      contact lens wearers (28.4 kU (18)/microgram) (p < 0.05), when compared with
      healthy individuals (39.4 kU (22.2)/microgram). CONCLUSION: Impression cytology
      can be regarded as a valuable method for obtaining samples of glycoconjugates of
      mucin. The decrease of sialylated chains observed with this method confirms the
      hypothesis that some quantitative changes in the tear film may be encountered in
      ocular surface disorders.

PMID- 9536891
TI  - Dermatitis artefacta presenting as a basal cell carcinoma--an important clinical
      sign missed.

PMID- 9536890
TI  - Immunopathology of uveitis.

PMID- 9536893
TI  - Indocyanine green angiography and idiopathic polypoidal choroidal vasculopathy.

PMID- 9536892
TI  - Application of mitomycin C 0.02% for 2 minutes at the end of pterygium surgery.

PMID- 9536894
TI  - Rhinogenic optic neuropathy caused bilateral loss of light perception.

PMID- 9536895
TI  - Bilateral subperiosteal haematoma after endoscopic sinus surgery.

PMID- 9536896
TI  - Reassessment of the PAS patterns in uveal melanoma.

PMID- 9536897
TI  - Radiology's Achilles' heel: error and variation in the interpretation of the
      Rontgen image.
AB  - The performance of the human eye and brain has failed to keep pace with the
      enormous technical progress in the first full century of radiology. Errors and
      variations in interpretation now represent the weakest aspect of clinical
      imaging. Those interpretations which differ from the consensus view of a panel of
      "experts" may be regarded as errors; where experts fail to achieve consensus,
      differing reports are regarded as "observer variation". Errors arise from poor
      technique, failures of perception, lack of knowledge and misjudgments. Observer
      variation is substantial and should be taken into account when different
      diagnostic methods are compared; in many cases the difference between observers
      outweighs the difference between techniques. Strategies for reducing error
      include attention to viewing conditions, training of the observers, availability
      of previous films and relevant clinical data, dual or multiple reporting,
      standardization of terminology and report format, and assistance from computers.
      Digital acquisition and display will probably not affect observer variation but
      the performance of radiologists, as measured by receiver operating characteristic
      (ROC) analysis, may be improved by computer-directed search for specific image
      features. Other current developments show that where image features can be
      comprehensively described, computer analysis can replace the perception function
      of the observer, whilst the function of interpretation can in some cases be
      performed better by artificial neural networks. However, computer-assisted
      diagnosis is still in its infancy and complete replacement of the human observer
      is as yet a remote possibility.

PMID- 9536898
TI  - A comparison of conventional mammographic magnification, ultra high magnification
      and industrial magnification radiography in the radiographic detection of
      microcalcifications within core biopsies of the breast.
AB  - The objective was to compare conventional magnification radiography (CMR), ultra
      high magnification radiography (UHMR) and industrial magnification radiography
      (IMR) in the detection of microcalcifications in breast core biopsies. 440 core
      biopsies were examined in 1.8-fold CMR and in 7-fold UHMR using a prototype unit.
      A subgroup of 59 core biopsies were also examined in 10-fold IMR. Number, size,
      and demarcation of microcalcifications, as well as tissue contrast, were
      evaluated. Only 67% of the microcalcifications seen with UHMR were detected by
      CMR and 78% of the core biopsies showing calcifications in UHMR were calcified in
      CMR. Only 38% and 58% of microcalcifications verified by IMR were identified by
      CMR and UHMR, respectively. 47% and 63% of the core biopsies showing
      calcifications in IMR were calcified in CMR and UHMR, respectively. Tissue
      contrast of IMR was superior to both other modalities. On the other hand,
      increased cost and time will probably prohibit the use of IMR for specimen
      radiography in routine clinical examinations. In conclusion, UHMR identifies
      substantially more core biopsies with microcalcifications than CMR, thus
      potentially reducing the number of core biopsies needed for histological
      analysis. IMR allowed the detection of approximately 50%/160% more
      microcalcifications than UHMR/CMR, thus rendering it the reference mode.

PMID- 9536899
TI  - Intravenous contrast media: are they being administered safely in radiology
      departments?
AB  - A recent Royal College of Radiologists (RCR) publication is entitled Advice on
      The Management of Reactions to Intravenous Contrast Media. This study aims to
      determine whether radiology departments are adhering to the essential points,
      covered in the guidelines, regarding prevention, early recognition and prompt
      treatment of adverse reactions, and whether they are adequately equipped for the
      proposed contrast media reaction management protocols. A questionnaire was
      formulated and sent to the superintendent radiographers of 295 radiology
      departments in the United Kingdom of whom 233 (79%) replied. This was
      specifically directed at the use of intravenous contrast media in intravenous
      urography. In almost all departments there was provision for basic life support
      training, regular checking of equipment and drugs, and prompt access to emergency
      medical help. Certain "first line" drugs and monitoring equipment were not
      instantly accessible in the majority of institutions. Most departments did not
      adequately supervise post-injection patients and did not conform to the
      guidelines referring to the administration of intravenous contrast to children.
      Certain areas of the guidelines are being neglected by many radiology departments
      and there is still much to be done to improve the safety of intravenous contrast
      medium injection.

PMID- 9536900
TI  - Clinicians' interpretation of the indeterminate ventilation-perfusion scan
      report.
AB  - Most patients with suspected pulmonary embolism are initially investigated by
      radio-nuclide ventilation-perfusion (VQ) scanning. Approximately 70% of VQ scans
      are "indeterminate". Further investigations should be considered in such patients
      in order to establish a definitive diagnosis. However, these investigations are
      rarely requested in patients with indeterminate scans in our institution. We
      therefore decided to review the casenotes of such patients to determine their
      subsequent management. Over a 9 month period, 131 (32%) out of a total of 413
      consecutive VQ scans were reported as indeterminate. The casenotes of 111 of
      these patients (65 female, 46 male, mean age 65 years, range 17-91 years) were
      reviewed. 52 of the 111 patients (46%) were treated on clinical grounds without
      further investigation; 12 patients (11%) had further investigation; and in 39 of
      the cases (35%) the VQ scan report was misinterpreted. 20 (38%) of the 52
      patients managed on clinical grounds were treated for pulmonary embolus with
      anticoagulation and 26 (50%) were not anticoagulated. Of the 12 patients who were
      investigated further, nine had lower limb Doppler ultrasound and three had
      contrast venography. No patients had pulmonary angiography. Of the 39 cases where
      the VQ report was misinterpreted, the result was misquoted in the casenotes of 37
      (95%) as negative for PE and none of these patients were anticoagulated, and in
      two cases (5%) it was misquoted as positive for PE and anticoagulant therapy was
      instituted. The misunderstanding was observed in all clinical firms. Such
      misinterpretation may have significant implications, since 30-40% of patients
      with indeterminate scans may have had PE. Our findings suggest that clinicians
      need to be better informed of the significance of an indeterminate VQ scan
      result.

PMID- 9536901
TI  - MRI of lumbar spondylosis: a comparison of sagittal T2 weighted and three
      sequence examinations.
AB  - The aim of this study was to determine whether a single T2 weighted sagittal
      sequence could replace the conventional three sequence examination of the lumbar
      spine. The T2 weighted sagittal image of 79 lumbar spine MRI examinations were
      retrospectively reported by three radiologists. Features relating to degenerative
      disease were recorded and an assessment made of whether further sequences were
      likely to add information. On a separate occasion the T1 weighted and T2 weighted
      sagittal and T2 weighted axial sequences were reported blind in relation to the
      initial assessment. Areas of disagreement were resolved by consensus opinion. The
      T2 weighted sequence was compared with the three sequences, taking the three
      sequence examination as the standard. Disc protrusions were diagnosed from the T2
      weighted sagittal images with a sensitivity of 38% and a specificity of 97%. 22
      discs reported as a disc bulge on the T2 weighted sequence were re-classified as
      a disc protrusion on axial images because of their focal nature. Central canal
      stenosis was diagnosed on the T2 weighted sagittal sequence with a sensitivity of
      60% and a specificity of 95%. After assessing the T2 weighted sequence, it was
      thought unlikely that further sequences would add extra information in 60% of
      cases (48/79). However, further information was obtained in 21% of these cases
      (10/48) when all the sequences were assessed. The extra information gained by
      using all three sequences was considered to be of greater benefit than the time
      saved by using a single T2 sagittal sequence. Other diagnoses where the
      additional sequences proved helpful are discussed.

PMID- 9536902
TI  - Ultrasound diagnosis of metastatic melanoma of the gallbladder.
AB  - The abdominal ultrasound examinations of 464 patients with malignant melanoma
      performed over a 3 year period were reviewed. 23 (5.2%) had soft tissue material
      attached to the gallbladder wall and projecting into the lumen. Four of these
      were polyps of less than 1 cm which were thought to be benign, while the
      remaining 19 had abnormalities likely to be metastatic melanoma. Upper abdominal
      ultrasound examinations are frequently requested for staging purposes in patients
      with thick high grade malignant melanoma or clinical suspicion of metastases.
      Ultrasound clearly identifies the gallbladder and biliary tree in the vast
      majority of patients and is generally regarded as the imaging modality of choice
      for suspected gallbladder pathology. As autopsy studies have confirmed the
      incidence of gallbladder metastases from malignant melanoma to be 15-20%, a
      careful review of the gallbladder is advocated when abdominal ultrasound
      examinations are performed on patients with malignant melanoma.

PMID- 9536903
TI  - Evaluation of tibial cortical bone by ultrasound velocity in oriental females.
AB  - In order to evaluate the feasibility of detecting bone status by measuring
      cortical ultrasound velocity, ultrasonic transmission velocity of the anterior
      cortex of shin was measured on 175 normal Chinese females aged 31-75 years (mean
      52.3 +/- SD 9.1 years). The data were compared with bone mineral density (BMD) of
      the lumbar spine and/or hip measured by dual energy X-ray absorptiometry (DXA),
      which was performed on the same day as speed of sound (SOS) examination.
      Comparison was made with SOS of Caucasian women previously reported in the
      literature. SOS of three volunteers measured by two different operators were also
      enrolled in our study for precision testing. The mean value of SOS of the 175
      females was 3850.7 +/- 119.3 m s-1 (range: 3411.7-4220.5 m s-1), the peak value
      being in the fourth decade. The rate of decrease of transmission velocity per
      decade from fourth decade to fifth decade was 1.7%, while that of fifth decade to
      sixth decade was 2.2% and that of sixth decade to seventh decade was 4.0%. The
      interoperative and intraoperative coefficient variance with and without
      reposition were under 0.32%. SOS moderately correlated with BMD at different
      sites, the best correlation being with the lumbar spine anteroposterior
      projection (r = 0.509; p < 0.0001, Pearson's test). There were significant
      differences in SOS between pre- and post-menopausal groups (p = 0.01, ANOVA
      test), and between peri- and post-menopausal groups (p = 0.02), but there was no
      correlation of body weight and height with SOS. SOS also inversely correlated
      with age and post-menopausal duration. The mean value of SOS in our study was
      similar to that of Caucasians, but the rate of decrease over 50 years of age was
      faster. The rate of decline of tibial cortical SOS was similar to that of
      trabecular bone as previously reported in the literature. As there is a
      significant decrease of SOS in older females, and older Oriental females suffer
      from an accelerated cortical bone loss, it is concluded that cortical bone SOS
      may be a useful method for detecting potential osteoporotic patients in this
      ethnic group.

PMID- 9536904
TI  - A comparison of image quality on 28 mammography X-ray sets in the UK.
AB  - Image quality has been assessed using three different phantoms on 28 mammographic
      X-ray units in the National Health Service Breast Screening Programme within the
      UK. The results show only relatively minor differences between different models
      of X-ray unit and between the 14 associated film processors, but more marked
      differences between different film-screen combinations. Medium screens give
      significantly lower image quality scores than fine screens from the same
      manufacturer. It is suggested that, to improve mammographic image quality, a
      change of screen type may bring greater benefit than a change of X-ray set model,
      as well as being much more cost effective.

PMID- 9536905
TI  - Patient doses from standard and spiral CT of the head using a fast twin-beam
      system.
AB  - Investigations were carried out on a novel type of CT scanner, the Elscint CT
      Twin, for comparison and optimization of the patient dose caused by standard and
      spiral CT of the head. For selected CT parameters, organ doses of the Alderson
      head phantom were measured with thermoluminescent dosemeters. Organ doses were
      also calculated using the normalized computed tomography dose index (CTDIn)
      combined with organ dose conversion factors. Then effective doses were deduced.
      For standard and spiral head CT examinations brain, red bone marrow and bone
      surface receive the main contributions to effective dose. This amounts to 0.9 and
      0.8 mSv for routine standard and spiral CT, respectively, if the combination
      "dual-slice" mode, 250 mAs per rotation, 5 mm nominal slice width and a packing
      factor of 1.0, is applied. In clinical practice, for spiral CT head examinations
      the effective dose has been reduced to 0.7 mSv while guaranteeing adequate image
      quality, as assessed by determination of low and high contrast resolution. The
      effective dose values obtained are in the lower part of the range of values
      published in the literature. The dose determinations showed that, from the aspect
      of radiation protection of the patient, CT examinations with nominal slice widths
      between 0.5 and 1 mm as well as packing factors greater than 1.0 should be
      restricted to really necessary cases.

PMID- 9536906
TI  - CT standard protocols are of limited value in assessing actual patient dose.
AB  - In the last 10 years the use of computed tomography in radiodiagnosis has
      increased markedly and CT scanners are now present in most district general
      hospitals. Modern CT scanners are versatile in their operation and offer the
      operator a wide choice in exposure parameters which affect the doses received by
      the patients. As CT is a major contributor to medical radiation doses, the
      National Radiological Protection Board (NRPB) recommends that an estimate of
      typical patient dose should be made for commonly used local scanning protocols. A
      survey has been undertaken in the Anglia and Oxford region covering 12 CT
      scanners. Common procedures were chosen, concentrating on those most frequently
      carried out and giving higher effective doses. These included routine heads,
      routine chests, high resolution chests and abdomen/pelvis examinations.
      Questionnaires were sent out to each CT centre to collect data on standard
      protocols and to record the procedure used for five actual patients for each
      examination type thus enabling a comparison of the two methodologies. This study
      has shown that many examinations are tailored to the individual patient size and
      clinical indications, particularly in the chest/abdomen/pelvis. Thus, assessing
      doses based on collecting standard protocols may not give a true indication of
      the effective doses being received by particular patients.

PMID- 9536907
TI  - A model to estimate the dose to tumour following intracavity administration of
      radioimmunoconjugates to patients with malignant gliomas.
AB  - Patients who have relapsed following primary treatment for malignant glioma and
      have undergone further surgical debulking have been treated with an anti-human
      neural cell adhesion molecule (NCAM) MoAb linked to either Iodine-131 or Yttrium
      90. These reagents are introduced into the tumour resection cavity via an Ommaya
      reservoir. Pharmacokinetic and imaging studies indicate that the
      radioimmunoconjugate remains within the cavity for a protracted period of time.
      In this manuscript we develop a dosimetric model to predict the dose delivered to
      the rim of tissue surrounding the resection cavity. The model takes into account
      variables such as the diameter of the cavity and the degree of antibody binding
      which is achieved. Whilst the calculated doses to the wall of the cavity are
      relatively inaccurate due to our inability to measure factors such as diffusion
      and heterogeneity in antibody uptake, the model illustrates the potential
      benefits and pitfalls that can result from targeting the two radionuclides. It is
      hoped that as increasing interest is shown in this type of "liquid brachytherapy"
      other groups will find it useful to apply the model to allow comparisons to be
      made between our targeting strategy and those developed by other individuals.

PMID- 9536908
TI  - A phase I trial of neutron brachytherapy for the treatment of malignant gliomas.
AB  - We performed a phase I trial to test the feasibility of neutron brachytherapy
      using californium-252 (252Cf) as the sole source of radiation, and to determine
      the maximum tolerable dose (MTD), for the treatment of malignant gliomas.
      Previous studies using external beam neutron radiation have shown that neutrons
      are capable of totally eradicating malignant gliomas. However, in most cases,
      fatal widespread radiation necrosis resulted. Radioactive implants are a logical
      method of increasing the dose to the tumour and decreasing the dose to normal
      brain. 252Cf is a relatively stable neutron-emitting isotope suitable for implant
      therapy. The study was an open ended dose-escalation study. All radiation was
      delivered by using only 252Cf implants, without external beam therapy of any
      type. The first dose step was 900 neutron cGy (ncGy); each subsequent step was
      increased by 100 ncGy. Three patients with newly diagnosed malignant gliomas were
      entered at each dose step, and the number was increased to six patients in dose
      steps at which necrosis of brain occurred. The study ended when two patients at
      any dose step developed radiation necrosis of brain outside the prescribed
      radiation field. 33 patients were entered into the study. 10 patients developed
      scalp necrosis associated with scalp doses above 900 ncGy. The study ended when
      two patients at the 1300 ncGy dose step developed radiation necrosis of brain. We
      conclude: (1) neutron brachytherapy using 252Cf as the sole source of radiation
      is a feasible treatment for malignant gliomas; (2) the scalp tolerates less
      neutron radiation than the brain; (3) the MTD (and the recommended dose for a
      phase II trial) of interstitial neutron brachytherapy is 1200 ncGy.

PMID- 9536909
TI  - Outcome of 259 patients with primary proliferative polycythaemia (PPP) and
      idiopathic thrombocythaemia (IT) treated in a regional nuclear medicine
      department with phosphorus-32--a 15 year review.
AB  - 259 patients with primary proliferative polycythaemia (PPP) and idiopathic
      thrombocythaemia (IT) have been treated with 32P over the last 15 years. Complete
      follow-up data were obtained in 238 patients. PPP was the diagnosis in 183
      patients and 76 patients had IT. The sex ratio in PPP was male/female 1.1:1 and
      in IT 1:1.4. Patients' ages ranged from 28 to 95 years (median 72 years). The
      number of 32P administrations per patient ranged from 1 to 13 (median 2) and the
      total administered activity per patient ranged from 81.4 to 4162 MBq (median 496
      MBq). The outcome showed a normalization of the full blood count in 50% of
      patients after a single administration of 32P and in 73% after two treatments. 13
      patients (5.5%) developed myelofibrosis; 18 (7.6%) developed leukaemia while
      other cancers arose in 19 patients (8%). 32P therapy proved to be of particular
      value in the elderly. 32P is easy to administer and is cost effective, compared
      with the alternative of chemotherapy where good compliance and frequent hospital
      visits are required.

PMID- 9536910
TI  - Effect of routine mammography practice on tumour size of a registry-based series
      of breast cancer cases compared with those observed in a screening cohort.
AB  - Routine mammography (MX) practice based on self-referral is considered not to be
      susceptible to monitoring at the population level. Invasive breast cancer cases
      notified to the Romagna Cancer Registry between 1989 and 1991 (total 654) were
      stratified by MX experience and were compared for the proportion of lesions
      greater than 2 cm in size (T2+) with cases observed in the study group of the
      Swedish Two Counties Screening Trial (TCST). Any MX more than 6 months prior to
      diagnosis was considered a previous routine examination. The proportion of cases
      registered in Romagna within 6-11 months of the most recent MX was quite similar
      to that shown by the interval cases of the TCST (50% vs 53%). T2+ cases
      registered in Romagna 12-23 months (27%) and 24-35 months (19%) after previous MX
      were similar in frequency to those detected at second and later screens in the
      TCST (22%). For longer intervals, the percentage of large tumours in the Romagna
      series increased, up to 45% among the cases registered more than 48 months since
      last MX (p < 0.0001). The whole group of cases with previous MX in Romagna and
      its counterpart in the TCST (i.e. interval cases + cases detected at second and
      later screens) had the same size distribution (35% vs 34%). The frequency of
      large tumours in the total series from Romagna was greater than in the total
      study group of the TCST (45% vs 36%, p < 0.0001). The difference was entirely
      accounted for by the cases with no previous MX.

PMID- 9536911
TI  - Cholesterol granuloma of the breast presenting as an intracystic papilloma.
AB  - Cholesterol granuloma of the breast is a rare benign condition. It is often
      clinically and radiologically indistinguishable from breast carcinoma. A case of
      cholesterol granuloma which manifested as an intracystic papilloma on ultrasound
      is described. This unusual ultrasonographic appearance has not previously been
      reported.

PMID- 9536912
TI  - Magnetic resonance imaging of subcutaneous diffuse neurofibroma.
AB  - A 31-year-old woman presented with increasing pain and tenderness of a long
      standing soft tissue mass on her back. MRI showed a network of interconnecting
      tubular areas, which were T1 isointense and T2 hyperintense relative to skeletal
      muscle, and displayed marked Gd-DTPA enhancement. The lesion was situated within
      the subcutaneous fat. Clinically and radiologically, this mass was considered to
      be a subcutaneous venous haemangioma. Histological examination of the excised
      mass showed a diffuse neurofibroma with ectatic vessels and entrapped adipose
      tissue. Similar MRI appearances of subcutaneous haemangioma and diffuse
      neurofibroma may result in failure to make the correct diagnosis and in
      inappropriate management.

PMID- 9536913
TI  - CT and MRI features of cavernous haemangioma of internal auditory canal.
AB  - A left internal auditory canal (IAC) cavernous haemangioma is reported in a 45
      year-old Saudi male. The lesion was associated with rapidly deteriorating hearing
      loss and facial nerve dysfunction. CT showed a calcified enhanced IAC lesion
      while T1 weighted MRI showed an isointense contrast enhancing lesion bulging into
      the porus acousticus. The imaging features of the three usual IAC lesions-
      meningioma, acoustic neuroma and cavernous haemangioma--were compared.
      Calcification/ossification appear more commonly in cavernous haemangioma than in
      the other two lesions while facial nerve dysfunction is a clinical hallmark of
      IAC cavernous haemangioma.

PMID- 9536914
TI  - Spontaneous renal pseudoaneurysm rupture presenting as acute intraabdominal
      haemorrhage.
AB  - A 39-year-old man with a known history of end-stage renal disease presented with
      hypovolaemic shock and acute abdominal pain. Blood-stained peritoneal fluid was
      present. Right perirenal and extensive mesenteric haematomas were seen at
      laparotomy and CT. Right renal arteriography demonstrated a small renal artery
      pseudoaneurysm, and embolization was performed. The patient later developed
      intractable sepsis and died despite nephrectomy and drainage of the infected
      haematomas. Although there is an increasing trend towards conservative management
      of spontaneously ruptured kidneys from benign causes, embolization followed by
      early surgery should be considered in cases of extensive intraabdominal
      haemorrhage.

PMID- 9536915
TI  - The ultrasound appearances of neonatal renal vein thrombosis.
AB  - Renal vein thrombosis (RVT) is the most frequently occurring vascular condition
      in the new-born kidney. The predisposing factors include dehydration, sepsis,
      birth asphyxia, maternal diabetes, polycythaemia and the presence of an
      indwelling umbilical venous catheter. (RVT) may present clinically with a flank
      mass, haematuria, hypertension or renal failure. Many imaging modalities have
      been employed, but ultrasound is the technique most commonly used in the
      evaluation of neonates with suspected RVT. Thrombosis commences in the small
      renal veins and subsequently propagates via larger interlobar veins to the main
      renal vein and inferior vena cava (IVC). The ultrasound appearances depend upon
      the stage at which the examination is performed and extent of the thrombus.
      Initially, the interlobular and interlobar thrombus appears as highly echogenic
      streaks. These streaks commence in a peripheral, focal segment of the involved
      kidney and only persist for a few days. In the first week the affected kidney
      swells and becomes echogenic with prominent echopoor medullary pyramids. Later,
      the swelling increases and the kidney becomes heterogenous with loss of
      corticomedullary differentiation. Grey scale ultrasound readily demonstrates
      thrombus within the renal vein and IVC. Adrenal haemorrhage is a recognized
      association and may be identified ultrasonically. Colour Doppler scanning
      provides additional information. In the early stages of RVT, colour Doppler may
      demonstrate absent intrarenal and renal venous flow. Ultimately, the kidney may
      recover, show focal scarring or become atrophic. Thus, ultrasound provides an
      accessible and reliable tool in the assessment of suspected neonatal RVT.

PMID- 9536916
TI  - Case of the month. Painless testicular nodularity in a young man.

PMID- 9536917
TI  - Matrix metalloproteinases: implication in vascular matrix remodelling during
      atherogenesis.
AB  - 1. The matrix metalloproteinases are a family of at least 16 zinc-dependent
      endopeptidases possessing catalytic activity against extracellular matrix
      components. Some members of this family have been implicated in vascular matrix
      remodelling in the pathogenesis of atherosclerosis. 2. A common, naturally
      occurring variant has been identified in the promoter of the stromelysin gene
      with one allele having a run of five adenosines (5A) and the other having six
      adenosines (6A). Functional analyses have shown that the 6A allele has a lower
      promoter activity than the 5A allele, which is probably attributable to
      preferential binding of a putative transcriptional repressor protein. 3. In
      patients with coronary artery disease, the 6A allele has been found to be
      associated with progression of atherosclerosis assessed by sequential
      quantitative angiography. 4. In conclusion, the matrix metalloproteinases may be
      over-expressed in certain locations in atherosclerotic plaques, which might
      contribute to local destruction of connective tissue and thus plaque rupture. In
      the majority of lesional areas, however, matrix synthesis is likely to outstrip
      matrix degradation, because matrix accumulation is a major feature of most
      atheromas. This imbalance favouring matrix deposition is likely to be exacerbated
      in individuals with the 6A6A genotype in whom stromelysin expression is lower due
      to the weaker stromelysin promoter.

PMID- 9536918
TI  - Peripheral vascular response to mild indirect cooling in patients with homozygous
      sickle cell (SS) disease and the frequency of painful crisis.
AB  - 1. In homozygous sickle cell (SS) disease, skin cooling is a common precipitating
      factor of the painful crisis which is associated with avascular necrosis of
      active bone marrow. Since skin cooling does not directly induce sickling, we have
      investigated the nature of the reflex vascular responses to mild cooling in SS
      patients in a steady state of the disease and compared them with their history of
      painful crises. 2. Experiments were performed in Jamaica on 60 male SS patients
      and 30 matched control subjects with normal haemoglobin (AA) genotype. Forearm
      blood flow (FBF) was measured by venous occlusion plethysmography and mean
      arterial pressure (MAP) by a Finapres device: forearm vascular resistance (FVR)
      was calculated as MAP/FBF. Cutaneous erythrocyte flux in forearm and hand was
      monitored by a laser Doppler meter. The contralateral hand was immersed in cool
      water at 16 degrees C for 2 min, 6 times, at random intervals of 0.5-3 min. 3.
      The first cool immersion evoked an increase in MAP, cutaneous vasoconstriction
      and a net increase in FVR in both AA and SS subjects. However, the direction of
      change in FVR varied between individuals such that 18 AA subjects showed an
      increase in FVR (constrictor group) while 12 showed a decrease in FVR, indicating
      vasodilatation in forearm muscle (dilator group). In contrast, 50 SS subjects
      showed an increase in FVR and only 10 showed a decrease in FVR. The proportion of
      subjects who showed net vasoconstriction was significantly greater in the SS than
      in the AA group (83% versus 60%, P = 0.03, chi 2 test). 4. By the sixth cool
      stimulus, the 'dilator' group of AA subjects showed no change in FVR while the
      'dilator' group of SS patients showed an increase in FVR. We suggest that forearm
      muscle vasodilatation was the characteristic component of the alerting/defence
      response to novel or noxious stimuli which habituates on repetition. 5. In the
      whole group of SS patients, baseline values of cutaneous vascular resistance and
      FVR increased between stimuli, indicating persistent vasoconstriction, and the
      sixth cool stimulus still evoked cutaneous vasoconstriction and a net increase in
      FVR. In contrast, AA subjects showed an increase in baseline FVR between stimuli,
      but the sixth cool stimulus had no significant effect on cutaneous vascular
      resistances, or FVR. 6. In SS patients there were no associations between the
      direction of change in FVR evoked by the first cool stimulus and forearm
      circumference or skinfold thickness, concentrations of haemoglobin or fetal
      haemoglobin. However, the frequency of painful crises was significantly greater
      in the 'constrictor' group than in the 'dilator' group (0.36 versus 0.12/year, P
      = 0.04, Mann-Whitney test). 7. These results indicate that the primary reflex
      vasoconstrictor response evoked by mild cooling is stronger and more persistent
      in SS patients than in AA subjects and is particularly strong in SS patients who
      are most prone to painful crises. The results are consistent with the hypothesis
      that skin cooling may precipitate the painful crisis by causing reflex
      vasoconstriction in muscle, and possibly in bone marrow, so diverting blood flow
      away from the active marrow.

PMID- 9536919
TI  - Influences on adrenaline-induced thermogenesis in obese women and relationship to
      cardiovascular responses.
AB  - 1. In order to evaluate factors influencing thermogenesis in obesity, energy
      expenditure was measured before and during an adrenaline infusion (25 ng min-1 kg
      1 ideal body weight for 30 min) in 22 obese females. 2. Thermogenic responses
      were related to body morphology, age and biochemistry. In addition, thermogenic
      responses were related to cardiovascular responses by simultaneously measuring
      blood pressure, pulse rate and cardiac output using Doppler sonography. 3.
      Resting energy expenditure was predicted by body weight, lean body mass and fat
      mass. 4. Adrenaline-induced thermogenesis was predicted by fasting insulin, low
      basal respiratory quotient and body fat. 5. There was a significant relationship
      between the cardiac output and thermogenic responses to adrenaline (r = 0.63 P <
      0.015) but there was no relationship to the heart rate or blood pressure
      responses. For every 1% increase in energy expenditure, there was a 5% increase
      in cardiac output. 6. In conclusion, the factors predicting resting energy
      expenditure and adrenaline-induced thermogenesis are different. Increased lipid
      oxidation and central fat distribution (with hyperinsulinaemia) are associated
      with a greater thermogenic response. The proportionately greater cardiac output
      responses may have implications for thermogenic agents designed to induce weight
      loss.

PMID- 9536920
TI  - Lack of effect of vitamin E on L-arginine-responsive endothelial dysfunction in
      patients with mild hypercholesterolaemia and coronary artery disease.
AB  - 1. Dietary supplementation with vitamin E reduces ischaemic events in patients
      with established coronary artery disease and improves endothelial function in
      cholesterol-fed rabbits. We examined whether such dietary supplementation with
      vitamin E improves endothelial function in patients with mild
      hypercholesterolaemia and coronary artery disease. 2. Twenty patients (total
      cholesterol 6.8 +/- 1.1 mmol/l, mean +/- SD) with angiographically documented
      coronary artery disease were randomly allocated to receive placebo (n = 10) or
      vitamin E, 400 i.u. daily, (n = 10) for 8 weeks. Endothelium-dependent and
      independent vasodilatation within forearm vasculature was assessed by brachial
      artery infusion of acetylcholine (co-infused with saline vehicle and L-arginine)
      and nitroprusside before and after supplementation. 3. Plasma concentrations of
      vitamin E increased from 32.9 +/- 3.8 to 69.1 +/- 11.8 mumol/l (means +/- SE) in
      the vitamin E-supplemented group (P < 0.01) but did not change significantly in
      the placebo group. Lipid profiles remained similar before and after
      supplementation in both groups. Forearm blood flow responses to acetylcholine
      (7.5 and 15 micrograms/min) and nitroprusside (3 and 10 micrograms/min) were
      similar before and after supplementation in both groups. Acute intra-arterial
      administration of L-arginine (10 mg/min) augmented the response to acetylcholine
      (15 micrograms/min) in both groups before and after supplementation to a similar
      degree (mean augmentation: 60 +/- 18%, P < 0.01). 4. Acute administration of L
      arginine reverses endothelial dysfunction in forearm vasculature of patients with
      mild hypercholesterolaemia and coronary artery disease but supplementation with
      vitamin E (400 i.u. daily) for 8 weeks does not reverse L-arginine-responsive
      endothelial dysfunction.

PMID- 9536921
TI  - Plasma levels of adrenomedullin in patients with acute myocardial infarction.
AB  - 1. Adrenomedullin, a newly identified vasorelaxant peptide, participates in the
      regulation of the cardiovascular system. To investigate the pathophysiological
      significance of adrenomedullin in patients with acute myocardial infarction, we
      measured plasma levels of adrenomedullin. 2. Cardiac catheterization was
      performed on admission, after 1 day, and after 4 weeks in 36 patients with acute
      myocardial infarction. We measured plasma levels of adrenomedullin, atrial
      natriuretic peptide and brain natriuretic peptide in the right atrium, pulmonary
      artery and aorta. 3. Plasma levels of adrenomedullin in the right atrium (mean +/
      SEM) were significantly increased on admission (4.2 +/- 2.6 h) in patients with
      acute myocardial infarction (10.6 +/- 1.0 pmol/l) compared with controls (5.2 +/-
      0.3 pmol/l, P < 0.01). In addition, plasma levels of adrenomedullin were further
      elevated in patients with congestive heart failure (12.3 +/- 1.4 pmol/l) compared
      with patients without congestive heart failure (7.8 +/- 0.6 pmol/l, P < 0.01). In
      patients with congestive heart failure, plasma adrenomedullin on admission
      significantly correlated with atrial natriuretic peptide and brain natriuretic
      peptide. 4. These results suggest that plasma adrenomedullin increases in the
      early phase of acute myocardial infarction and that volume expansion may be one
      of the additional stimuli for the release of adrenomedullin in patients with
      acute myocardial infarction complicated by congestive heart failure.

PMID- 9536922
TI  - Pharmacological characterization of coronary small arteries from pigs with
      chronic ischaemic myocardial remodelling.
AB  - 1. The effect of chronic ischaemic myocardial remodelling on small coronary
      artery reactivity in vitro was studied in a newly developed pig model. 2. Pigs
      were subjected to selective intracoronary embolizations with microspheres in the
      left anterior descending artery and circumflex artery causing scattered
      myocardial fibrosis. After an observation period of 130 days, heart dimensions
      and ejection fraction were determined with magnetic resonance imaging. Small
      arteries were isolated from the left ventricle and mounted as ring preparations
      in a myograph. Control arteries were taken from matched non-embolized pigs. 3.
      Compared with control pigs, end-systolic and diastolic volumes increased and left
      ventricular mass nearly doubled in embolized pigs. This indicates substantial
      myocardial hypertrophy, as the fraction area of fibrosis was only 12%. 4.
      Coronary small arteries preconstricted with 30 mmol/l KCI showed a normal
      contractile response to acetylcholine and 5-hydroxytryptamine. Sensitivity of the
      relaxation to bradykinin was nearly 3-fold increased and also slightly enhanced
      to isoprenaline in arteries from embolized pigs compared with controls, whereas
      relaxation to 5-hydroxytryptamine in the presence of ketanserin was similar.
      After inhibition of nitric oxide synthase with NG-nitro-L-arginine the
      sensitivity to acetylcholine increased to a similar extent in arteries from
      embolized pigs and controls. NG-Nitro-L-arginine abolished the relaxing effects
      of bradykinin and of 5-hydroxytryptamine in the presence of ketanserin. 5. We
      conclude that both the contractile function of the smooth muscle cells and the
      endothelial production or action of nitric oxide is preserved or slightly
      enhanced in coronary small arteries from pigs with chronic myocardial
      remodelling.

PMID- 9536923
TI  - An early prenatal exposure to excess glucocorticoid leads to hypertensive
      offspring in sheep.
AB  - 1. Recent studies in animals have linked fetal exposure to excess maternal
      glucocorticoids with the later occurrence of cardiovascular disorders,
      particularly hypertension. 2. To test the hypothesis that prenatal treatment
      could impact on adult blood pressure two groups of pregnant ewes were transported
      from the farm to the Institute at either 22-29 days of pregnancy (pretreatment
      group 1) or 59-66 days of pregnancy (pretreatment group 2), subjected to 48 h
      treatment with dexamethasone (0.28 mg day-1 kg-1 for 2 days) and then returned to
      the farm. The control group remained at the farm for the entire pregnancy. Lambs
      were then studied at approximately 4, 10 and 19 months after birth. 3. The basal
      mean arterial pressure in pretreatment group 1 (80 +/- 1 mmHg at 124 days; 83 +/-
      1 mmHg at 309 days and 89 +/- 1 mmHg at 558 days; n = 6) was significantly
      different (P < 0.05 in all groups) from that in the control group of lambs (74 +/
      2 mmHg at 110 days; 76 +/- 1 mmHg at 323 days and 81 +/- 1 mmHg at 568 days; n =
      7). However, prenatal glucocorticoid exposure did not alter vascular sensitivity
      to noradrenaline, angiotensin II and adrenocorticotropic hormone in these sheep
      at any of the ages studied, nor did it affect basal or adrenocorticotropic
      hormone-induced concentrations of cortisol or basal plasma renin concentrations
      in the lambs at any age. 4. These data support the hypothesis that excess
      glucocorticoid exposure in early pregnancy, during a critical developmental stage
      or 'window', programmes higher blood pressure that persists in later life.

PMID- 9536924
TI  - Intravenous lactate prevents cerebral dysfunction during hypoglycaemia in insulin
      dependent diabetes mellitus.
AB  - 1. Intravenous lactate prevents cerebral dysfunction during hypoglycaemia in
      healthy volunteers. This study examines whether this also occurs in insulin
      dependent diabetes. Changes in four-choice reaction time, auditory brain stem
      response, and P300 latency were used as measures of cerebral function. 2. Ten
      subjects were studied twice at least 4 weeks apart. Blood glucose was maintained
      between 5 and 8 mmol/l for 1 h before starting a 60 m-unit min-1 m-2 stepped
      hyperinsulinaemic clamp, achieving blood glucose concentrations of 4.5, 3.3 and
      2.5 mmol/l. At one visit, 40 mumol min-1 kg-1 sodium lactate was infused, and at
      the other, normal saline. Cerebral function was measured at each blood glucose
      concentration. 3. Blood lactate rose to 3.32 +/- 0.06 mmol/l during lactate
      infusion compared with 0.9 +/- 0.03 mmol/l during saline infusion. Compared with
      the results at 4.5 mmol/l there were no significant changes at 3.3 mmol/l in any
      measure of cerebral function at either visit. At 2.5 mmol/l a significant
      increase in reaction time and P300 latency occurred with saline [mean change 33.1
      +/- 8.6 ms (P < 0.01) and 30.1 +/- 9.2 ms (P < 0.01) respectively] but not
      lactate [mean change -5.9 +/- 3.7 ms (P > 0.05) and -6 +/- 7.6 ms (P > 0.05)
      respectively]. No significant changes occurred in auditory brain stem response.
      The catecholamine response to hypoglycaemia was attenuated by lactate (P < 0.05
      for adrenaline and noradrenaline). 4. Thus intravenous lactate prevents cerebral
      dysfunction during hypoglycaemia in insulin-dependent diabetes.

PMID- 9536925
TI  - Angiotensin-converting enzyme inhibition does not correct early defects in renal
      and vascular permeability in diabetes mellitus.
AB  - 1. In diabetes mellitus a selective increase in the excretion of albumin
      generally precedes the occurrence of demonstrable loss of glomerular size
      selectivity. However, even in this (microalbuminuric) phase of diabetic
      nephropathy a defect in glomerular barrier function can be demonstrated during
      infusion of atrial natriuretic peptide. 2. The aim of this study was to
      investigate whether angiotensin-converting enzyme inhibition could prevent the
      proteinuric response to atrial natriuretic peptide in these patients. We
      performed infusions of atrial natriuretic peptide (0.01 microgram min-1 kg-1) in
      10 patients with insulin-dependent diabetes mellitus and microalbuminuria
      (urinary albumin excretion 90 +/- 44 mg/day), both before and after 1 month of
      treatment with enalapril (20 mg once daily). 3. Despite a 40% reduction in
      proteinuria, angiotensin-converting enzyme inhibition did not prevent the atrial
      natriuretic peptide-induced increase in protein excretion. Both before and during
      angiotensin-converting enzyme inhibition, atrial natriuretic peptide infusion
      resulted in a significant increase in the fractional excretion of large dextran
      molecules, which is compatible with an increase in flow through large
      unrestrictive 'shunt' pores. Atrial natriuretic peptide infusion also induced an
      increase in the transcapillary escape rate of albumin and angiotensin-converting
      enzyme inhibition also failed to prevent this effect of atrial natriuretic
      peptide on peripheral capillary permeability. 4. We conclude that angiotensin
      converting enzyme inhibition during 1 month does not correct the capillary
      barrier function defect in patients with diabetes mellitus and microalbuminuria
      that is unmasked by atrial natriuretic peptide infusion.

PMID- 9536926
TI  - Systemic nitric oxide synthase inhibition increases insulin sensitivity in man.
AB  - 1. Recent evidence shows that skeletal muscle blood flow is an important
      determinant of insulin sensitivity and that insulin-mediated vasodilatation is
      nitric oxide dependent. These results have given rise to the hypothesis that
      endothelial nitric oxide inhibition may decrease insulin sensitivity in humans.
      2. We examined this hypothesis directly by evaluating the effects of systemic
      nitric oxide synthase inhibition with NG-monomethyl L-arginine (3 mg h-1 kg-1) on
      whole-body glucose uptake (euglycaemic hyperinsulinaemic clamp) and calf blood
      flow (bilateral calf venous occlusion plethysmography) in 16 healthy male
      subjects in a randomized, double-blind, placebo-controlled, crossover study. 3.
      NG-Monomethyl L-arginine infusion was associated with a pressor effect (119/61 +/
      2/2 compared with 114/58 +/- 2/2 mmHg for placebo; P < 0.001), and a negative
      chronotropic response (57 +/- 2 compared with 62 +/- 2 beats/min for placebo; P <
      0.001). The glucose infusion rate was significantly increased after infusion of
      NG-monomethyl L-arginine (8.9 +/- 0.9 compared with 7.9 +/- 0.8 mg min-1 kg-1 for
      placebo; P = 0.002). Whole-body glucose uptake increased during the clamp, with
      values of 9.4 +/- 0.7 and 10.9 +/- 0.8 mg min-1 kg-1 for placebo and NG
      monomethyl L-arginine respectively (P = 0.036; 95% confidence interval 0.2,2.8).
      NG-Monomethyl L-arginine was associated with increased calf blood flow by
      comparison with placebo (P < 0.05, area under curve). 4. These data show for the
      first time that systemic inhibition of nitric oxide synthesis increases rather
      than decreases whole-body glucose uptake. We suggest that the higher skeletal
      muscle blood flow seen after NG-monomethyl L-arginine may explain the observed
      increase in whole-body glucose uptake.

PMID- 9536927
TI  - Pancreatic bile-salt-dependent lipase activity in serum of diabetic patients: is
      there a relationship with glycation?
AB  - 1. Pancreatic bile-salt-dependent lipase has been detected in human plasma where
      it has the capability to modify normal low- and high-density lipoprotein
      composition and structure and to reduce the atherogenicity of oxidized low
      density lipoprotein (Shamir R, Johnson WJ, Morlock-Fitzpatrick K, Zolfaghari R,
      Li L, Mas E, Lombardo D, Morel DW, Fisher EA. Pancreatic carboxyl ester lipase: a
      circulating enzyme that modifies normal and oxidized lipoproteins in vitro. J
      Clin Invest 1996; 97: 1696-704). 2. In the present study, we investigated the
      effect of glycation and particularly that of human serum albumin on the activity
      of bile-salt-dependent lipase. In vitro, bile-salt-dependent lipase activity
      decreased in the presence of human serum albumin; however, this was less
      pronounced in the presence of glycated human serum albumin. In vivo, bile-salt
      dependent lipase specific activity was about 2-fold higher in the sera of
      diabetic patients than in the sera of normal subjects. 3. A significant increase
      in the specific activity of bile-salt-dependent lipase related to the serum level
      of glycation was observed. The increase in bile-salt-dependent lipase specific
      activity was not related to the glucose concentration in serum suggesting that
      glycation of bile-salt-dependent lipase could not be involved in the observed
      effects. Although the stability of serum bile-salt-dependent lipase was important
      enough to allow a systemic action of the enzyme on lipoproteins, it could not
      explain the higher activity of the enzyme in diabetic serum. 4. We concluded that
      bile-salt-dependent lipase could be helpful against the premature development of
      atherosclerosis in diabetes.

PMID- 9536928
TI  - Carotenoids, retinol and tocopherols in patients with insulin-dependent diabetes
      mellitus and their immediate relatives.
AB  - 1. Patients with insulin-dependent diabetes mellitus are classified among the
      groups at risk for low vitamin status, and recent studies suggest that some
      degree of supplementation with antioxidants may be beneficial in helping to
      prevent certain long-term complications of diabetes mellitus. Our objective was
      to compare the status of the fat-soluble vitamins and antioxidant-related
      compounds in patients with well-defined insulin-dependent diabetes mellitus with
      that of their first-degree relatives, controlling seasonal and analytical
      variability as factors influencing the interpretation of the data. 2. Fifty-four
      patients with insulin-dependent diabetes mellitus, 214 non-diabetic, first-degree
      relatives (controls) and 236 unrelated controls were analysed for retinol,
      tocopherols (alpha and gamma) and main carotenoids in serum (beta-carotene, alpha
      carotene, beta-cryptoxanthin, lutein, zeaxanthin and lycopene) by means of a
      validated HPLC method. 3. Insulin-dependent diabetes mellitus was associated with
      lower retinol levels and higher levels of beta-carotene, alpha-carotene and beta
      cryptoxanthin than sex-matched, first-degree relatives. alpha-Tocopherol, the
      alpha-tocopherol/cholesterol ratio, gamma-tocopherol, lutein, zeaxanthin and
      lycopene showed no differences. Retinol and beta-carotene were the variables most
      closely associated with diabetes. 4. Patients with insulin-dependent diabetes
      mellitus showed lower serum retinol status together with higher concentrations of
      provitamin-A carotenoids. Serum fat-soluble antioxidant levels were greater than
      or equal to those in controls. According to the serum status observed,
      individuals with diabetes do not require supplementation with alpha-tocopherol or
      carotenoids, although the need for retinol supplementation in patients with
      marginal serum levels should be evaluated.

PMID- 9536929
TI  - Does total antioxidant status relate to outcome in very preterm infants?
AB  - 1. In healthy humans, a balance exists between oxygen-derived free-radical
      production and their removal by antioxidants. In preterm infants inadequate
      antioxidant defences may contribute to the pathogenesis of some of the
      complications of prematurity. 2. Plasma total antioxidant status and
      malondialdehyde concentration were measured during the first 11 days of life in
      25 infants to determine whether increased lipid peroxidation is associated with
      low extracellular antioxidant status. In a second group of infants, total
      antioxidant status was quantified within 12 h of birth, and subsequently on days
      4 and 10 to investigate the hypothesis that adverse neonatal outcome is
      associated with low antioxidant status. 3. There may be a weak negative
      correlation between the total antioxidant status of infants and the lipid
      peroxidation marker malondialdehyde in plasma (r = -0.24, P = 0.056, n = 89)
      during the first 11 days of life. In the second group of infants, total
      antioxidant status was found to be significantly related to plasma urate and
      bilirubin levels, but not to adverse neonatal outcomes such as chronic lung
      disease, intraventricular haemorrhage, retinopathy of prematurity or death. 4. If
      adverse neonatal outcomes are due to inadequate antioxidant defences, these are
      likely to be intracellular or localized rather than general extracellular
      deficiencies.

PMID- 9536930
TI  - Relationship between serum alkaline phosphatase and pyridoxal-5'-phosphate levels
      in hypophosphatasia.
AB  - 1. Hypophosphatasia is a disorder characterized by low serum levels of alkaline
      phosphatase (ALP) and a range of skeletal deformities. The levels of a number of
      phosphorylated metabolites, namely phosphoethanolamine and pyrophosphate, are
      characteristically raised. Levels of pyridoxal-5'-phosphate (PLP) have also been
      reported to be raised. 2. Hypophosphatasia is a rare disease and experience of
      measuring PLP in patients is lacking. We have had the chance to look at PLP
      levels in four families with hypophosphatasia, specifically to examine the
      quantitative relationship between ALP and PLP which has not been described
      before. 3. We confirmed that PLP levels are raised in hypophosphatasia and
      related to the disease severity. A significant negative linear relationship was
      found between the log PLP and log ALP (log PLP = 5.99-2.76 log ALP; r = -0.85, P
      < 0.001). 4. Measurement of PLP is simpler than some of the phosphorylated
      compounds, e.g. pyrophosphate. PLP may be a useful measure in patients with a
      suspected diagnosis of hypophosphatasia or for screening family members to detect
      potential heterozygotes and to monitor any response to therapy. 5. There did not
      appear to be any adverse clinical effects in relation to disturbed vitamin B6
      metabolism in hypophosphatasia. 6. Vitamin B6 is used therapeutically in a number
      of conditions with monitoring of PLP levels. In these conditions PLP levels
      should be interpreted in conjunction with the prevailing serum ALP levels as the
      metabolism of these compounds is closely inter-related.

PMID- 9536932
TI  - NOS inhibitors in colitis: a suitable case for treatment?

PMID- 9536931
TI  - Colonic responses to enteral tube feeding.

PMID- 9536933
TI  - Ambulatory manometry in dyspepsia: walking a thin line.

PMID- 9536934
TI  - Depressing acid, deconjugating bile.

PMID- 9536935
TI  - Coming clean on reuse of endoscopic equipment.

PMID- 9536936
TI  - Interleukin 10 is a growth factor for a population of regulatory T cells.
AB  - Induction and maintenance of peripheral tolerance are important mechanisms to
      maintain the balance of the immune system. In addition to the deletion of T cells
      and their failure to respond in certain circumstances, active suppression
      mediated by T cells or T-cell factors has been proposed as a mechanism for
      maintaining peripheral tolerance. However, the inability to isolate and clone
      regulatory T cells involved in antigen-specific inhibition of immune responses
      has made it difficult to understand the mechanisms underlying such suppression.
      Here, we show that chronic activation of both human and murine CD4+ T cells in
      the presence of interleukin (IL)-10 gives rise to CD4+ T-cell clones with low
      proliferative capacity, producing high levels of IL-10, low levels of IL-2 and no
      IL-4. These antigen-specific T-cell clones suppress the proliferation of CD4+ T
      cells in response to antigen, and prevent colitis induced in SCID mice by
      pathogenic CD4+CD45RBhigh splenic T cells. Thus IL-10 drives the generation of a
      CD4+ T-cell subset, designated T regulatory cells 1 (Tr1), which suppresses
      antigen-specific immune responses and actively downregulates a pathological
      immune response in vivo.

PMID- 9536937
TI  - Eradicating Helicobacter pylori reduces hypergastrinaemia during long-term
      omeprazole treatment.
AB  - BACKGROUND: Both proton pump inhibitor drug treatment and Helicobacter pylori
      infection cause hypergastrinaemia in man. AIMS: To determine whether eradicating
      H pylori is a means of reducing hypergastrinaemia during subsequent proton pump
      inhibitor treatment. METHODS: Patients with H pylori were randomised to treatment
      with either anti-H pylori or symptomatic treatment. One month later, all received
      four weeks treatment with omeprazole 40 mg/day for one month followed by 20
      mg/day for six months. Serum gastrin concentrations were measured before and
      following each treatment. RESULTS: In the patients randomised to anti-H pylori
      treatment, eradication of the infection lowered median fasting gastrin by 48% and
      meal stimulated gastrin by 46%. When gastrin concentrations one month following
      anti-H pylori/symptomatic treatment were used as baseline, omeprazole treatment
      produced a similar percentage increase in serum gastrin in the H pylori infected
      and H pylori eradicated patients. Consequently, in the patients in which H pylori
      was not eradicated, median fasting gastrin concentration was 38 ng/l (range 26
      86) at initial presentation and increased to 64 ng/l (range 29-271) after seven
      months omeprazole, representing a median increase of 68% (p < 0.005). In
      contrast, in the patients randomised to H pylori eradication, median fasting
      gastrin at initial presentation was 54 ng/l (range 17-226) and was unchanged
      after seven months omeprazole at 38 ng/l (range 17-95). CONCLUSION: Eradicating H
      pylori is a means of reducing the rise in gastrin during subsequent long term
      omeprazole treatment. In view of the potential deleterious effects of
      hypergastrinaemia it may be appropriate to render patients H pylori negative
      prior to commencing long-term proton pump inhibitor treatment.

PMID- 9536938
TI  - Influence of metronidazole resistance on efficacy of quadruple therapy for
      Helicobacter pylori eradication.
AB  - BACKGROUND: Metronidazole-containing eradication therapies are less effective for
      metronidazole resistant Helicobacter pylori. Although early data suggested
      improvement of the efficacy of bismuth triple therapy after the addition of acid
      suppressives, these findings were based on studies with small numbers of
      patients, incomplete post-eradication follow up, or omission of pretreatment
      susceptibility testing. AIMS: To study the efficacy of quadruple therapy in the
      Amsterdam area, where the efficacy of bismuth triple therapy has been proved to
      be affected by metronidazole resistance. PATIENTS AND METHODS: Eighty two
      consecutive dyspeptic H pylori positive patients with either metronidazole
      susceptible (group I) or metronidazole resistant H pylori strains (group II)
      received quadruple therapy for one week: omeprazole 20 mg twice daily; colloidal
      bismuth subcitrate 120 mg four times a day; tetracycline 500 mg four times a day;
      metronidazole 500 mg three times a day. Susceptibility to metronidazole was
      determined by the E-test. RESULTS: Intention to treat analysis showed that H
      pylori infection had been cured in 42/43 patients (98%) in group I and 32/39
      patients (82%) in group II (p = 0.02). CONCLUSION: The efficacy of quadruple
      therapy is significantly impaired in patients infected with metronidazole
      resistant H pylori. Therefore a non-metronidazole-containing regimen should
      preferably be used in areas known to have a high prevalence of pretreatment
      metronidazole resistance.

PMID- 9536939
TI  - Anticipation in familial Crohn's disease.
AB  - BACKGROUND: Offspring with a family history of Crohn's disease have an earlier
      age of onset than their parents. This might be due to genetic anticipation,
      characterised by earlier and/or more severe disease in subsequent generations.
      AIMS: To investigate the possibility of genetic anticipation in affected parent
      child pairs with Crohn's disease from France and Belgium. PATIENTS AND METHODS:
      In a cohort of 160 multiply affected families with Crohn's disease, 57 parent
      first affected child pairs were detected. Clinical characteristics (age at
      diagnosis, disease extent, and type) of both parents and children were registered
      and compared. RESULTS: Children were younger than their parents at diagnosis in
      48/57 (84%) pairs. The median age at diagnosis was 16 years younger in children
      than in parents (p < 0.0001). However, the difference was related to the age at
      diagnosis in the parents and was not present in 12 parent-child pairs with an
      early age at diagnosis for the parents. In most cases, disease extent and type
      were not considered more severe in children than in parents. Parental sex
      affected neither age at diagnosis nor extent and type of disease in children.
      CONCLUSION: Patients in the second affected generation acquire their disease at
      an earlier time in life in some but not all familial cases of Crohn's disease.
      Several explanations including genetic anticipation and environmental factors
      might explain this phenomenon.

PMID- 9536940
TI  - General and cancer specific mortality of a population based cohort of patients
      with inflammatory bowel disease: the Florence Study.
AB  - BACKGROUND: A population based epidemiological study identified all the patients
      diagnosed with ulcerative colitis (UC) or Crohn's disease (CD) resident in the
      Florence area in the period 1978-1992. AIMS: To assess the mortality of
      unselected patients with inflammatory bowel disease (IBD) in a Mediterranean
      country. METHODS: Overall, 920 patients (689 UC and 231 CD) were followed until
      death or end of follow up (31 December 1996). Information on vital status was
      available for all except eight patients (0.9%); 70 deaths were identified (23 in
      patients with CD and 47 in patients with UC). Expected deaths were estimated on
      the basis of five year age group, gender, and calendar year national mortality
      rates. Standardised mortality ratios (SMR) and 95% confidence intervals were
      calculated. RESULTS: General mortality was significantly lower than expected in
      UC (SMR 0.6; 95% confidence interval 0.4 to 0.8), due to a reduced number of
      cardiovascular and, possibly, smoking related deaths. Cancers of the respiratory
      tract were significantly reduced in UC but tended to be increased in patients
      with CD. These latter patients had not only an increased cancer mortality but
      also a 40% increased risk of dying for all causes already evident in the first
      five year follow up period and persisting thereafter. In contrast, in patients
      with UC, SMRs were initially very low but tended to increase steadily over the
      follow up period. Gastrointestinal deaths were particularly increased in patients
      with CD, but only moderately in those with UC. Overall, there was some evidence
      of a twofold increased mortality for colorectal cancer, the risk being highest
      for rectal cancers in patients with UC. A non-significant excess of deaths due to
      haemolymphopoietic malignancies and suicides was also observed. CONCLUSIONS: This
      study, the first in a Mediterranean country, supports the existence of two
      divergent mortality patterns for patients with UC and CD, possibly explained by
      differences in smoking habits and by a greater severity of CD.

PMID- 9536941
TI  - Increased expression of an inducible isoform of nitric oxide synthase and the
      formation of peroxynitrite in colonic mucosa of patients with active ulcerative
      colitis.
AB  - BACKGROUND: Increased production of reactive metabolites of oxygen and nitrogen
      has been implicated in chronic inflammation of the gut. The object of this study
      was to examine the magnitude and location of nitric oxide synthase (NOS) activity
      and peroxynitrite formation in the colonic mucosa of patients with ulcerative
      colitis in relation to the degree of inflammation. SUBJECTS: Thirty three
      patients with active ulcerative colitis (17 with mild or moderate inflammation,
      16 with severe inflammation). METHODS: Inducible NOS activity was determined in
      the colonic mucosa by measuring the conversion of L-arginine to citrulline in the
      absence of calcium. The localisation of NOS and nitrotyrosine immunoreactivity
      was assessed immunohistochemically using the labelled streptavidin biotin method.
      RESULTS: Inducible NOS activity increased in parallel with the degree of
      inflammation of the mucosa. Expression of inducible NOS was found not only in the
      lamina propria, but also in the surface of the epithelium. Peroxynitrite
      formation as assessed by nitrotyrosine staining was frequently observed in the
      lamina propria of actively inflamed mucosa. CONCLUSIONS: Nitric oxide and
      peroxynitrite formation may play an important role in causing irreversible
      cellular injury to the colonic mucosa in patients with active ulcerative colitis.

PMID- 9536943
TI  - Use of mesalazine slow release suppositories 1 g three times per week to maintain
      remission of ulcerative proctitis: a randomised double blind placebo controlled
      multicentre study.
AB  - BACKGROUND: Daily administration of rectal formulations of mesalazine is
      effective in preventing relapse of ulcerative proctitis. Maintenance of remission
      with lower doses would be an advantage. AIM: The efficacy of mesalazine
      suppositories (Pentasa) 1 g three times a week v placebo to maintain remission in
      patients with cryptogenetic proctitis was studied. METHODS: Ninety five patients
      with cryptogenetic proctitis were randomised within two weeks of remission to
      receive for one year or until relapse three suppositories per week of either
      Pentasa (n = 48) or placebo (n = 47). In the case of a relapse, the patients
      received one suppository/day. RESULTS: It was found that 25 of 48 subjects v 18
      of 47 remained in remission in the mesalazine and placebo groups respectively.
      The relapse rate was lower in the mesalazine group for the following time
      intervals: 0-90 days (19% v 38%, p = 0.035), 0-180 days (29% v 54%, p = 0.017), 0
      270 days (38% v 60%, p = 0.031), and 0-365 days (48% v 62%, p = 0.18). Treatment
      of relapse with one suppository/day induced remission in 11 of 18 and 2 of 26
      patients in the mesalazine and placebo groups respectively (p = 0.001). Overall,
      61% v 28% patients remained in the protocol and were in remission at one year (p
      = 0.001). Tolerance was good. CONCLUSION: Mesalazine suppositories 1 g three
      times a week are effective for preventing relapses of cryptogenetic proctitis.
      Increasing the dose to 1 g/day is effective in a high proportion of subjects who
      relapsed.

PMID- 9536942
TI  - Bone mineral density and nutritional status in children with chronic inflammatory
      bowel disease.
AB  - BACKGROUND: Osteoporosis has been reported in adult patients with inflammatory
      bowel disease. AIMS: To evaluate bone mineral density (BMD), nutritional status,
      and determinants of BMD in children with inflammatory bowel disease. PATIENTS:
      Fifty five patients (34 boys and 21 girls, age range 4-18) were studied; 22 had
      Crohn's disease and 33 ulcerative colitis. METHODS: Lumbar spine and total body
      BMD, and body composition were assessed by dual energy x ray absorptiometry
      (DXA). Results were expressed as standard deviation scores (SDS). Lean body mass
      was also assessed by bioelectrical impedance analysis (BIA). Yearly measurements
      during two years were performed in 21 patients. RESULTS: The mean SDS of lumbar
      spine BMD and total body BMD were significantly lower than normal (-0.75 and 
      0.95, both p < 0.001). Height SDS and body mass index SDS were also decreased.
      The decrease in BMD SDS could not be explained by delay in bone maturation. The
      cumulative dose of prednisolone correlated negatively with lumbar spine BMD SDS
      (r = -0.32, p < 0.02). Body mass index SDS correlated positively with total body
      BMD SDS (r = 0.36, p < 0.02). Patients with Crohn's disease had significantly
      lower lumbar spine and total body BMD SDS than patients with ulcerative colitis,
      even after adjustment for cumulative dose of prednisolone. In the longitudinal
      data cumulative dose of prednisolone between the measurements correlated
      negatively with the change in lumbar spine and total body BMD SDS. Lean tissue
      mass measured by DXA had a strong correlation with lean body mass measured by BIA
      (r = 0.98). CONCLUSIONS: Children with inflammatory bowel disease have a
      decreased BMD. Children with Crohn's disease have a higher risk of developing
      osteopaenia than children with ulcerative colitis. Corticosteroid therapy and
      nutritional status are important determinants of BMD in these patients.

PMID- 9536944
TI  - Rapid modulation of electrolyte transport in Caco-2 cell monolayers by
      enteropathogenic Escherichia coli (EPEC) infection.
AB  - BACKGROUND AND AIMS: The pathophysiology of enteropathogenic Escherichia coli
      (EPEC) diarrhoea remains uncertain. EPEC adhere to enterocytes and transduce
      signals which produce a characteristic "attaching and effacing" (A/E) lesion in
      the brush border membrane. The present in vitro study was designed to determine
      whether signal transduction by EPEC also influences electrolyte transport.
      METHODS: Caco-2 cell monolayers were rapidly infected with wild type EPEC strain
      E2348/69, or the signal transduction-defective mutant 14.2.1(1), and mounted in
      Ussing chambers. RESULTS: Strain E2348/69 stimulated a rapid but transient
      increase in short circuit current (Isc) which coincided with A/E lesion
      formation; this Isc response was absent on infection with strain 14.2.1(1). While
      the initial rise in Isc induced by E2348/69 was partially (approximately 35%)
      dependent on chloride, the remainder possibly represents an influx of sodium and
      amino acid(s) across the apical membrane. CONCLUSIONS: The study directly shows
      that, after initial adhesion, EPEC induce major alterations in host cell
      electrolyte transport. The observed Isc responses indicate a rapid modulation of
      electrolyte transport in Caco-2 cells by EPEC, including stimulation of chloride
      secretion, for which signal transduction to host cells is a prerequisite.

PMID- 9536945
TI  - Interferon gamma induces differential upregulation of alpha and beta chemokine
      secretion in colonic epithelial cell lines.
AB  - BACKGROUND: Production of chemoattractant factors by the intestinal epithelium
      may contribute to mucosal infiltration by inflammatory cells in inflammatory
      bowel disease. Secretion of the alpha chemokine interleukin 8 (IL-8), a
      neutrophil chemoattractant, has been widely studied, but little is known about
      epithelial secretion of beta chemokines, which are preferentially involved in
      recruiting monocytes. AIMS: To investigate the profiles of alpha and beta
      chemokine secretion in colonic cell lines and their differential modulation by
      interferon gamma (IFN-gamma), a product of activated T lymphocytes and natural
      killer cells. METHODS AND RESULTS: HT29-19A, a model of the CT secretory crypt
      cell, exhibited a parallel secretion of the alpha chemokines IL-8 and GRO alpha,
      which could be markedly upregulated by tumour necrosis factor alpha (TNF-alpha)
      and IL-1 beta. These cells showed no significant expression of the beta
      chemokines RANTES (regulated upon activation T cell expressed and secreted), MIP
      1 alpha (macrophage inflammatory protein 1 alpha), and MCP-1 (monocyte
      chemotactic protein 1) under these conditions, but IFN-gamma in combination with
      TNF-alpha caused a dose dependent induction of RANTES and MCP-1 secretion. This
      was accompanied by a marked increase of RANTES mRNA. In contrast, IFN-gamma had
      no significant effect on TNF-alpha stimulated IL-8 secretion. Caco-2 cells, with
      features more typical of villus absorptive cells, were relatively poor secretors
      of alpha chemokines but secreted high levels of MCP-1 in response to IL-1 beta.
      IFN-gamma did not influence alpha or beta chemokine secretion in these cells.
      CONCLUSIONS: These studies suggest that intestinal epithelial cells may produce
      chemokines capable of attracting both neutrophils and monocytes. The ability of
      IFN-gamma to activate the expression of beta chemokines preferentially could
      facilitate the development of chronic inflammatory infiltrates.

PMID- 9536946
TI  - Expression of interleukin 1 beta and interleukin 1 beta converting enzyme by
      intestinal macrophages in health and inflammatory bowel disease.
AB  - BACKGROUND: In the lipopolysaccharide (LPS) stimulated peripheral blood monocyte,
      the precursor form of interleukin 1 beta (IL-1 beta, 31 kD) is processed by IL-1
      beta converting enzyme (ICE) to the mature, bioactive form (17 kD). IL-1 beta is
      a proinflammatory cytokine which is likely to have a role in the pathogenesis of
      inflammatory bowel disease (IBD). AIMS: To investigate the expression and
      processing of IL-1 beta and ICE by tissue macrophages from normal and IBD colonic
      mucosa. METHODS: Mucosal biopsy specimens and lamina propria cells from normal
      and IBD colons were studied by reverse transcription polymerase chain reaction
      (RT-PCR), western blot analysis, and ELISA (enzyme linked immunosorbent assay).
      RESULTS: Normal colonic macrophages synthesised only the precursor form of IL-1
      beta whereas in IBD the mature form was also produced. Similarly, cells from
      normal colonic mucosa synthesised ICE as the precursor (p45) only, whereas
      macrophages from IBD colons produced active (p20) ICE. Ac-Tyr-Val-Ala-Asp-CHO, a
      specific peptide aldehyde inhibitor of ICE, significantly reduced the amount of
      mature IL-1 beta released by isolated IBD macrophages (from a median of 1.2
      (range 0.78-4.42) ng/ml to 0.43 (0.21-1.6) ng/ml; p < 0.01). CONCLUSIONS:
      Exposure of normal colonic macrophages to LPS only induces the production of the
      precursor form of IL-1 beta, because the cells fail to activate ICE. In contrast,
      IBD colonic macrophages are able to activate ICE and hence release mature IL-1
      beta in a manner similar to circulating monocytes. This is consistent with IBD
      macrophages being recently recruited from the circulating monocyte population.
      Targeted inhibition of ICE may represent a novel form of therapy in IBD.

PMID- 9536947
TI  - Developmental expression of mucin genes in the human gastrointestinal system.
AB  - BACKGROUND AND AIMS: Mucin glycoproteins play a key role in the normal function
      of the epithelium lining the gastrointestinal tract. The expression of mucin
      genes, MUC 3, 4, 5AC, 5B, 6, 7, and 8 in human fetal tissues was examined to
      establish the localisation and age of onset of expression of each mucin gene
      during human development. METHODS: Mucin gene expression was assayed by mRNA in
      situ hybridisation. RESULTS: Expression of MUC3 was detected in the small
      intestine and colon from 13 weeks gestation onwards and at low levels in the main
      pancreatic duct at 13 weeks only. MUC4 expression was seen at a low level in the
      colonic epithelium from 13 weeks of gestation but not elsewhere in the
      gastrointestinal tract. MUC5AC mRNA was detected in the colon at 17 weeks and at
      high levels in the stomach at 23 weeks. MUC6 transcripts were evident in the
      pancreatic ducts from 13 weeks of gestation and at high levels in the stomach at
      23 weeks. MUC5B, MUC7, and MUC8 transcripts were not detected. CONCLUSIONS: Mucin
      genes are expressed from the early mid-trimester of gestation in the developing
      human fetal gastrointestinal tract.

PMID- 9536948
TI  - Interleukin 1 beta and tumour necrosis factor alpha inhibit acid secretion in
      cultured rabbit parietal cells by multiple pathways.
AB  - BACKGROUND: The cytokines interleukin 1 beta (IL-1 beta) and tumour necrosis
      factor alpha (TNF-alpha) are inhibitors of gastric acid secretion when
      administered systemically. AIMS: To investigate the inhibitory effect of IL-1
      beta and TNF-alpha on cultured, acid secreting parietal cells in order to
      determine the mechanism of this inhibition. METHODS: Rabbit parietal cells were
      prepared by collagenase-EDTA digestion and counter flow elutriation. Acid
      secretory activity was assessed by aminopyrine accumulation. RESULTS: IL-1 beta
      and TNF-alpha inhibited basal and stimulated acid secretion in a dose dependent
      manner; near maximal effects were seen with both at 10 ng/ml. Inhibition was
      maximal with 15 minutes pretreatment but seen with up to 18 hours of
      preincubation. Both cytokines inhibited histamine, carbachol, gastrin, forskolin,
      and A23187 stimulated acid secretion but had no effect on stimulation by
      dibutyryl-cAMP. Inhibition of acid secretion was not accompanied by a change in
      radioligand binding to histamine H2 or gastrin/CCKB receptors. Pertussis toxin
      abolished the inhibitory effects on histamine and forskolin stimulation. The
      tyrosine kinase inhibitor herbimycin reduced the inhibitory effects of TNF-alpha
      against all stimuli but only reduced the effects of IL-1 beta against histamine
      and forskolin stimulation. CONCLUSIONS: IL-1 beta and TNF-alpha seem to inhibit
      parietal cell acid secretion by multiple pathways; the inhibition occurs at
      postreceptor level and involves pertussis toxin and tyrosine kinase dependent and
      independent pathways. Mucosal production of cytokines may be important in the
      regulation of gastric acid secretion.

PMID- 9536949
TI  - Ambulatory gastrojejunal manometry in severe motility-like dyspepsia: lack of
      correlation between dysmotility, symptoms, and gastric emptying.
AB  - BACKGROUND: Previous studies have failed to identify manometric patterns of
      gastrointestinal motor activity that can distinguish dyspepsia from health. AIMS:
      To test the hypothesis that the combined use of prolonged, ambulatory,
      antrojejunal manometry and computer aided analysis in patients selected for the
      severity of their symptoms could reveal new insights into gastrointestinal motor
      activity in patients with severe motility-like dyspesia. METHODS: Twenty four
      hour antrojejunal ambulatory manometry was performed in 14 patients and 10
      healthy volunteers. Parameters characterising digestive and fasted motility were
      obtained by a validated computer program and visual analysis. Scoring systems
      quantified the degree of dysmotility as well as the severity of symptoms. Gastric
      emptying times were measured in each patient. RESULTS: There was a high
      prevalence of antral and jejunal dysmotility both during the interdigestive
      period (71% of patients) and in the postprandial period (78%). During the
      interdigestive period there was a reduced incidence of antral and jejunal phases,
      a larger contribution of phase 2 during migrating motor complex cycles, and
      aberrant configuration of jejunal phase 3 in 29% of patients. Postprandially, the
      most frequent finding was antral (29% of patients) or jejunal (29%) hypomotility
      or hypermotility. Minute rhythm was present both during the postprandial (29% of
      patients) and the interdigestive period (21%). There was no positive correlation
      between symptom scores, gastric half emptying times, or motility scores.
      CONCLUSION: Even with the use of prolonged recordings and advanced computer aided
      analysis, it is not possible to identify a specific motor pattern which can
      discriminate patients with severe motility-like dyspepsia from those with other
      diseases or even healthy individuals. Clinical symptoms or gastric half emptying
      times are poor predictors of gastrointestinal dysmotility in patients with
      functional dyspepsia.

PMID- 9536951
TI  - Motor function of the proximal stomach and visceral perception in gastro
      oesophageal reflux disease.
AB  - BACKGROUND: The abnormally high postprandial rate of transient lower oesophageal
      sphincter relaxations seen in patients with reflux disease may be related to
      altered proximal gastric motor function. Heightened visceral sensitivity may also
      contribute to reporting of symptoms in these patients. AIMS: To assess motor
      function of the proximal stomach and visceral perception in reflux disease with a
      barostat. METHODS: Fasting and postprandial proximal gastric motility, sensation,
      and symptoms were measured in nine patients with reflux disease and nine healthy
      subjects. Gastric emptying of solids and liquids was assessed in six of the
      patients on a different day (and compared to historical controls). RESULTS:
      Minimal distending pressure and gastric compliance were similar in the two
      groups, whereas the patients experienced fullness at lower pressures (p < 0.05)
      and discomfort at lower balloon volumes (p < 0.005) during isobaric and
      isovolumetric distensions respectively. Maximal gastric relaxation induced by the
      meal was similar in the two groups. Late after the meal, however, proximal
      gastric tone was lower (p < 0.01) and the score for fullness higher (p < 0.01) in
      the reflux patients, in whom the retention of both solids and liquids in the
      proximal stomach was greater (p < 0.05). CONCLUSIONS: Reflux disease is
      associated with delayed recovery of proximal gastric tone after a meal and
      increased visceral sensitivity. The former may contribute to the increased
      prevalence of reflux during transient lower oesophageal sphincter relaxations and
      the delay in emptying from the proximal stomach, whereas both may contribute to
      symptom reporting.

PMID- 9536952
TI  - The effect of flufenamic acid on gastrointestinal myoelectrical activity and
      transit time in dogs.
AB  - BACKGROUND: Flufenamic acid, a fenamate, has been shown to alter markedly the
      membrane potential of small intestinal smooth muscle and increase intracellular
      calcium in single cells. AIMS: To determine the effects of flufenamic acid on
      myoelectrical motor activity and gastrointestinal transit in the intact animal.
      METHODS: Myoelectrical motor activity was recorded via seromuscular platinum
      electrodes sutured at regular intervals in the stomach and throughout the small
      intestine. Fasted and fed gastrointestinal transit was assessed using technetium
      99m (99mTc) as the radioactive marker linked to 1 mm amberlite pellets or added
      to the meal. RESULTS: Flufenamic acid (600 mg, intravenously) induced intense
      spike activity in the small intestine. The mean duration of irregular spike
      activity was 250 (7) minutes. Spike activity was more pronounced in the lower
      small intestine. Flufenamic acid also accelerated initial gastric emptying and
      markedly shortened transit time in the small intestine. In the fasted state the
      50% transit time in the small intestine was 54 (8) minutes with infusion of
      flufenamic acid compared with 105 (10) minutes in the control group; in the fed
      state 99mTc first reached the colon at 220 (10) minutes compared with 270 (12)
      minutes in the control group. CONCLUSIONS: Flufenamic acid had marked effects on
      both myoelectrical motor complex activity and small intestinal transit in the
      dog. The observed effects suggest that flufenamic acid may be of potential use as
      a prokinetic agent.

PMID- 9536950
TI  - Effect of gastric acid suppressants on human gastric motility.
AB  - BACKGROUND: The effect of histamine H2 receptor antagonists on gastric emptying
      is controversial. AIMS: To determine the effects of ranitidine, famotidine, and
      omeprazole on gastric motility and emptying. PATIENTS AND METHODS: Fifteen normal
      subjects underwent simultaneous antroduodenal manometry, electrogastrography
      (EGG), and gastric emptying with dynamic antral scintigraphy (DAS). After 30
      minutes of fasting manometry and EGG recording, subjects received either
      intravenous saline, ranitidine, or famotidine, followed by another 30 minutes
      recording and then three hours of postprandial recording after ingestion of a
      radiolabelled meal. Images were obtained every 10-15 minutes for three hours to
      measure gastric emptying and assess antral contractility. Similar testing was
      performed after omeprazole 20 mg daily for one week. RESULTS: Fasting antral
      phase III migrating motor complexes (MMCs) were more common after ranitidine
      (9/15 subjects, 60%), famotidine (12/15, 80%), and omeprazole (8/12, 67%)
      compared with placebo (4/14, 29%; p < 0.05). Postprandially, ranitidine,
      famotidine, and omeprazole slowed gastric emptying, increased the amplitude of
      DAS contractions, increased the EGG power, and increased the antral manometric
      motility index. CONCLUSIONS: Suppression of gastric acid secretion with
      therapeutic doses of gastric acid suppressants is associated with delayed gastric
      emptying but increased antral motility.

PMID- 9536953
TI  - Omeprazole induces altered bile acid metabolism.
AB  - BACKGROUND: It has been reported that the acidity of gastric contents could be an
      important factor in regulating jejunal flora. AIMS: To investigate the effects of
      omeprazole induced changes in gastric pH on jejunal flora and bile acid
      metabolism. METHODS: Twenty one patients with gastric ulcer and 19 healthy
      volunteers were studied. Deconjugation of bile acids was detected using a bile
      acid breath test. Jejunal fluid was aspirated using a double lumen tube with a
      rubber cover on the tip and deconjugation was examined using thin layer
      chromatography. Fat malabsorption was detected by a triolein breath test.
      RESULTS: In the bile acid breath test, expired breath samples from all patients
      and healthy volunteers showed significantly greater 14CO2 specific activity after
      omeprazole treatment (20 mg/day) than before treatment. Bacterial overgrowth was
      found in the jejunal fluid and gastric juice of both ulcer patients and healthy
      volunteers after omeprazole treatment. The following species were identified:
      Escherichia coli, Candida albicans, enterococcus, Lactobacillus bifidus,
      Bacteroides vulgatus, B uniformis, Eubacterium lentum, Eu parvum, and
      Corynebacterium granulosum. All of these species, except E coli and C albicans,
      deconjugate bile acids. There was a significant correlation between 14CO2
      activity and gastric pH, both before and after omeprazole treatment in both
      groups. The triolein breath test revealed impaired fat absorption in both groups
      after omeprazole treatment. CONCLUSIONS: Both patients with gastric ulcer and
      healthy volunteers exhibited increased deconjugation of bile acids caused by
      bacterial overgrowth in the jejunum and fat malabsorption after omeprazole
      treatment. The bacterial over-growth consisted of both anaerobes and aerobes with
      deconjugation ability and was probably associated with an omeprazole induced
      shift to neutral pH in the gastric juice.

PMID- 9536954
TI  - Inhibition of phenolsulphotransferase by salicylic acid: a possible mechanism by
      which aspirin may reduce carcinogenesis.
AB  - BACKGROUND: Recent epidemiological evidence has shown that chronic use of aspirin
      decreases susceptibility to bowel cancer. Animal studies have shown that
      sulphotransferase inhibitors coadministered with sulphation activated carcinogens
      dramatically reduce the incidence of cancer. AIMS: To investigate the effect of
      the main aspirin breakdown product, salicylic acid, on the P and M isoforms of
      phenolsulphotransferase from human platelets and colonic mucosa. METHODS:
      Platelets were obtained from healthy blood donors and isolated within 24 hours
      after donation. Samples of colonic mucosa were obtained at resection for non
      malignant disease. Phenolsulphotransferase activity was measured in cellular
      homogenates using a standard radiolabelling assay. RESULTS: Salicylic acid
      consistently and selectively inhibited the P form of phenolsulphotransferase at
      subtherapeutic concentrations in both tissue samples. A 50% inhibition of
      sulphation by the P phenolsulphotransferase occurred at salicylic acid
      concentrations of about 40 and 130 microM in platelets and bowel mucosa
      respectively. M phenolsulphotransferase was virtually unaffected by salicylic
      acid up to a concentration of 1.5 mM (the therapeutic plasma concentration for
      salicylates when treating rheumatoid arthritis is about 1-2 mM). CONCLUSION: The
      action of salicylic acid on P phenolsulphotransferase, by preventing the
      excessive activation of carcinogens, is a possible additional pathway by which
      aspirin can reduce cancer risk.

PMID- 9536955
TI  - The relationship between intrahepatic portal systemic shunts and microsphere
      induced portal hypertension in the rat liver.
AB  - BACKGROUND: Portal hypertension is associated with gross haemodynamic
      disturbances characterised by high cardiac output, low peripheral vascular
      resistance, increased splanchnic blood flow, and portal systemic shunting. AIMS:
      To study the relationship between intrahepatic portal systemic shunts and
      microsphere induced portal hypertension in the rat liver. METHODS: Different
      sized microspheres were sequentially injected into the portal vein of male Wistar
      rats. RESULTS: Steady state portal venous pressure was increased by 102.2 (35.6)%
      (14.9 (3.6) mm Hg) and 272.3 (78.0)% (24.0 (2.2) mm Hg) above the basal pressure
      following sequential injections of 15 and 80 microns diameter microspheres,
      respectively. Sequential injection of 15, 40, and 80 microns diameter
      microspheres in either ascending or descending order of size did not generate
      further increases in portal venous pressure. A single injection of 1.8 x 10(5) 80
      microns microspheres consistently produced a steady state portal venous pressure
      of 19.0 (1.3) mm Hg but did not approach the much higher value of 36.6 (43.2) mm
      Hg measured during clamping of the portal vein. These data indicate that the
      opening of patent intrahepatic shunts was responsible for the reduced pressures
      observed during microsphere injections and further evidence for this was provided
      by the location of microspheres in the pulmonary vascular bed. The elevation in
      portal venous pressure achieved by microsphere injections was not significantly
      different to that produced in rats subjected to partial portal vein ligation
      (20.7 (0.5) mm Hg, p > 0.05). Wedged hepatic venous pressure decreased from 6.7
      (0.7) to 3.0 (0.6) mm Hg following injection of 80 microns microspheres,
      suggesting a decrease in total hepatic blood flow. Conversely, injection of 15
      microns microspheres induced an increase in wedged hepatic venous pressure from
      7.0 (1.0) mm Hg to 12.4 (1.8) mm Hg, indicating a localised redistribution of
      blood flow at the presinusoidal level of the portal venous vascular network and
      increased intrahepatic shunt flow. CONCLUSION: It is suggested that there may be
      a protective pathophysiological role for these shunts when the liver is subjected
      to changes which induce acute portal hypertension.

PMID- 9536956
TI  - Acute effect of propranolol and isosorbide-5-mononitrate administration on renal
      blood flow in cirrhotic patients.
AB  - BACKGROUND: Propranolol and isosorbide-5-mononitrate (ISMN) are increasingly used
      in the prophylaxis of variceal haemorrhage in cirrhosis. However, recent studies
      have suggested that these drugs may compromise renal function, possibly by
      reducing renal blood flow. AIMS: To assess the acute effects of propranolol and
      ISMN on renal blood flow and other haemodynamic parameters in cirrhosis. PATIENTS
      AND METHODS: Twenty six cirrhotic patients were given either 80 mg propranolol,
      20 mg ISMN, or a combination of the two drugs. Unilateral renal blood flow (RBF),
      azygos blood flow (AZBF), hepatic venous pressure gradient (HVPG), mean arterial
      pressure (MAP), and heart rate (HR) were recorded prior to and one hour after
      drug administration. RESULTS: Propranolol caused a reduction in HR (p < 0.005),
      AZBF (p < 0.01), and HVPG (p = 0.05), but no change in MAP or RBF (454.1 (77.3)
      versus 413.9 (60.3) ml/min). ISMN reduced MAP (p < 0.005) and HVPG (p < 0.01),
      but had no effect on HR, AZBF, or RBF (302.5 (49.4) versus 301.7 (58.8) ml/min).
      Combined treatment reduced MAP (p < 0.005), AZBF (p < 0.05), and HVPG (p =
      0.002), but HR and RBF (419.2 (62.6) versus 415.1 (61.1) ml/min) remained
      unchanged. CONCLUSIONS: Despite the anticipated changes in other haemodynamic
      parameters, acute propranolol and/or ISMN administration did not reduce RBF.
      These drugs do not seem to compromise RBF in cirrhosis.

PMID- 9536957
TI  - Effect of endoscopic sphincterotomy on gall bladder bile lithogenicity and
      motility.
AB  - BACKGROUND: Endoscopic sphincterotomy has been shown to inhibit stone formation
      in the gall bladder of experimental animals. AIMS: To investigate the alterations
      in bile composition and gall bladder motility after endoscopic sphincterotomy.
      PATIENTS: A study was performed of gall bladder bile composition and gall bladder
      motility in patients with gallstone disease ((n = 20; age 40-60 years, median age
      55 years: seven men), with gall bladder calculi (n = 12) and with diseased gall
      bladder (chronic inflammation) without gall bladder calculi (n = 8)), who had
      received endoscopic sphincterotomy for common bile duct stones. Age and sex
      matched disease controls comprised 20 patients with gallstone disease but without
      stones and an intact sphincter of Oddi (with gall bladder calculi (n = 10) and
      diseased gall bladder without gall bladder calculi (n = 10)). METHODS: Gall
      bladder motility was assessed by ultrasound. Duodenal bile collected by
      nasoduodenal tube after stimulation of gall bladder by intravenous ceruletid
      infusion was analysed for cholesterol, phospholipid, and bile acid
      concentrations, cholesterol saturation index, and nucleation time. RESULTS: There
      was a significant reduction in mean (SEM) fasting volume (12.5 (1.7) ml v 26.4
      (2.5) ml; p < 0.001) and mean (SEM) residual volume (4.34 (0.9) ml v 14.7 (0.98)
      ml; p < 0.001), and increase in mean (SEM) ejection fraction (65.7 (4.2)% v 43.6
      (5.52)%; p < 0.001) and mean (SEM) rate constant of gall bladder emptying (
      0.031/min v -0.020/min; p < 0.01) in patients who had been subjected to
      endoscopic sphincterotomy. Median nucleation time was significantly longer (17
      days v 6 days; p < 0.006) in treated patients. There was a reduction in total
      mean (SEM) lipid concentrations (6.73 (0.32) g/dl v 7.72 (0.84) g/dl; p < 0.05),
      cholesterol (5.6 (1.5) mmol/l v 10.3 (2.23) mmol/l; p < 0.001) and CSI (0.72
      (0.15) v 1.32 (0.31); p < 0.001). There was no significant change in mean (SEM)
      phospholipid (25.6 (3.5) mmol/l v 23.4 (6.28) mmol/l) and bile acid (93.7 (7.31)
      mmol/l v 105.07 (16.6) mmol/l) concentrations. CONCLUSIONS: After endoscopic
      sphincterotomy there was enhanced contractility of the gall bladder, accompanied
      by a prolongation of nucleation time and reduction in cholesterol saturation
      index.

PMID- 9536960
TI  - Report of the Working Party of the Endoscopy Committee of the British Society of
      Gastroenterology on the reuse of endoscopic accessories.

PMID- 9536958
TI  - Conclusive evidence of endotoxaemia in biliary obstruction.
AB  - BACKGROUND: Endotoxaemia is implicated in the pathophysiology of obstructive
      jaundice. The EndoCab enzyme linked immunosorbent assay (ELISA) is a novel assay
      which measures endogenous antibody (IgG) to the inner core region of circulating
      endotoxins (ACGA). AIMS: To investigate the significance of endotoxaemia in
      biliary obstruction using the EndoCab assay and assess the specificity of the
      humoral response to endotoxin compared with an exogenous antigenic challenge
      (tetanus toxoid, TT). METHODS: Three groups of adult male Wistar rats were
      studied: no operation, sham operation, and bile duct ligation for 21 days (BDL).
      In the second study, rats rats received prior immunisation with TT. RESULTS: In
      the preliminary experiment, plasma ACGA was significantly increased in the BDL
      group (306.6 (18.3)% versus 119.9 (6.7)% and 105.2 (4.6)% in the sham and no
      operation groups, respectively; p < 0.001). Although the mean endotoxin
      concentration in the BDL group was greater than that in the control groups this
      was not significant. There was a strong positive correlation between ACGA and
      endotoxin concentrations (p = 0.0021). In the second study mean ACGA after 21
      days of BDL was significantly elevated (267.1 (31.2)% versus 101.6 (21.2)% at
      baseline, p < 0.0001). ACGA was unaffected in the other two groups. TT antibody
      concentrations fell in all three groups; only in the BDL group was the fall
      significant (97.6 (5.3)% versus 78.8 (4.2)% at baseline, p < 0.05). CONCLUSIONS:
      The specific rise in ACGA supports the hypothesis that endotoxin has an integral
      role in the pathophysiology of obstructive jaundice. The production of anticore
      glycolipid antibodies specifically reflects systemic endotoxaemia in this model.
      The EndoCab assay provides a novel, sensitive, and specific method for endotoxin
      detection.

PMID- 9536959
TI  - The role of microsatellite instability in gastric carcinoma.

PMID- 9536961
TI  - Stress protein response in human oesophageal epithelium may be influenced by the
      ex vivo culture technique.

PMID- 9536962
TI  - pH-dependent gating in the Streptomyces lividans K+ channel.
AB  - Because of its size, high levels of expression, and unusual detergent stability,
      the small K+ channel from Streptomyces lividans (SKC1) is considered to be an
      ideal candidate for detailed structural analysis. In this paper, we have used
      planar lipid bilayers and radiotracer uptake experiments to study purified and
      reconstituted SKC1, in an attempt to develop a bulk assay for its functional
      characterization. In channels reconstituted into liposomes with external pH 3.5
      and intravesicular pH 7.5, a time-dependent SKC1-catalyzed 86Rb+ uptake was
      observed. This cationic influx was blocked by Ba2+ ions with a Ki (external) of
      0.4 mM and was shown to have the following selectivity sequence: K+ > Rb+ > NH4+
      >> Na+ > Li+. In experiments with external pH 7.5 or in liposomes containing no
      channels, no 86Rb+ uptake was detected. When SKC1 was incorporated into planar
      lipid bilayers, we failed to observe significant single-channel activity at
      neutral pH but detected frequent multiple-channel openings a pH < 5.0. These
      results indicate that under these experimental conditions SKC1 behaves as a pH
      gated K+ channel in which protonation of one or more residues promotes channel
      opening. At acidic pH and symmetrical 200 mM KCl solutions, SKC1 showed numerous
      brief openings with a main single-channel conductance of 135 pS and a
      subconductance state of 70 pS. Channel open probability showed a slight voltage
      dependence, with higher activities observed at negative potentials, a fact which
      may suggest that the protonation site lies within the transmembrane electrical
      field. Attempts to determine the pKa of channel activation were obscured by
      intrinsic limitations of the 86Rb+ flux assay. However, it appears to be lower
      than pH 4.0. Limited proteolysis experiments demonstrated that SKC1 reconstitutes
      vectorially, almost exclusively in the right-side-out configuration, indicating
      that the protonation site responsible for channel opening is located at the
      extracellular face of the channel. These results point toward a potentially novel
      gating mechanism for SKC1 and open the possibility of using transmembrane-driven
      radiotracer influx experiments as a reliable bulk functional assay for
      reconstituted SKC1.

PMID- 9536963
TI  - Menaquinone-7 in the reaction center complex of the green sulfur bacterium
      Chlorobium vibrioforme functions as the electron acceptor A1.
AB  - Photosynthetically active reaction center complexes were prepared from the green
      sulfur bacterium Chlorobium vibrioforme NCIMB 8327, and the content of quinones
      was determined by extraction and high-performance liquid chromatography. The
      analysis showed a stoichiometry of 1.7 molecules of menaquinone-7/reaction
      center. No other quinones were detected in the isolated reaction centers, whereas
      membrane preparations also contained chlorobiumquinone. The possible involvement
      of quinones in electron transport was investigated by electron paramagnetic
      resonance (EPR) spectroscopy. A highly anisotropic radical was detected by Q-band
      EPR spectroscopy in both membranes and isolated reaction centers following dark
      reduction with sodium dithionite and photoaccumulation at 205 K. At 34 GHz, the
      EPR spectrum is characterized by a g tensor with gxx = 2.0063, gyy = 2.0052, gzz
      = 2.0020 and delta B of 0.7 mT, consistent with its identification as a quinone.
      This spectrum is highly similar in terms of g values and line widths to
      photoaccumulated A1- in photosystem I of Synechococcus sp. PCC 7002. The results
      indicate that menaquinone-7 in the green sulfur bacterial reaction center is
      analogous to phylloquinone in photosystem I.

PMID- 9536964
TI  - TNF but not IL-1 decreases pancreatic acinar cell survival without affecting
      exocrine function: a study in the perfused human pancreas.
AB  - Substantial quantities of interleukin-1 beta (IL-1 beta) and tumor necrosis
      factor-alpha (TNF-alpha) are produced within the pancreatic parenchyma during
      acute pancreatitis. Recent evidence suggests that IL-1 beta and TNF-alpha
      propagate acute pancreatitis and intensify the resulting pancreatic acinar cell
      death. This study examines the direct effect of IL-1 beta and TNF-alpha on
      pancreatic acinar cells. Human pancreata (n = 6), harvested during organ
      procurement, were perfused ex vivo through the splenic artery using a sterile,
      oxygenated colloid solution. Each pancreas was perfused with either recombinant
      human IL-1 beta or TNF-alpha for 2 h and subsequently with the cholecystokinin
      analogue caerulein (positive control). Venous effluent was collected continuously
      and amylase and lipase were determined at 15-min intervals. Pancreatic histology
      was graded at baseline and following cytokine and caerulein perfusion. To examine
      the long-term effects of these cytokines on acinar cell viability, additional in
      vitro studies utilized the AR42J acinar cell line which was exposed to either IL
      1 beta or TNF-alpha with survival determined daily by MTT assay. Perfusion of the
      human pancreas with either IL-1 beta or TNF-alpha did not alter amylase, lipase,
      or histology. Caerulein did induce pancreatitis as measured by increased amylase,
      lipase, and pancreatic histology. Survival of pancreatic acinar cells decreased
      when they were incubated with TNF-alpha but not IL-1 beta. Although present in
      large amounts within the pancreas during acute pancreatitis, IL-1 beta and TNF
      alpha have no direct effect on acinar cell viability or exocrine function acutely
      nor do they induce pancreatitis. When present for more than 24 h, however, TNF
      alpha but not IL-1 beta has a dramatic effect on acinar cell survival.

PMID- 9536965
TI  - Incidence and characteristics of patients with hand ischemia after a hemodialysis
      access procedure.
AB  - The purpose of this study was to determine the clinical characteristics of
      chronic renal failure patients who developed hand ischemia in the limb carrying
      the dialysis angioaccess. A retrospective review of the charts of 352 patients
      who underwent 409 upper extremity arteriovenous access, and who were subsequently
      diagnosed as steal syndrome, was performed at the Emory University Hospital
      between February 1992 and January 1997. Hand ischemia occurred after 13 of 299
      arteriovenous grafts (4.3%) and after 2 of 110 direct forearm arteriovenous
      fistulas (1.8%). Six patients developed ischemic manifestations immediately
      postoperatively, 2 in the first week, 4 after 1 month, and 1 after 1 year.
      Thirteen occurred in association with the primary access procedure. Two cases
      occurred following graft thrombectomy and outflow dilatation. Seven patients were
      mildly symptomatic with dialysis-induced pain, coldness, or numbness; 8 patients
      developed severe ischemic manifestations in the form of sensory loss in 3, severe
      intolerable pain with impalpable pulse in 3, and digital gangrene and amputation
      in 2, one of whom developed an unhealed amputation stump and required a higher
      amputation level with satisfactory healing of the revised stump. Three patients
      were treated conservatively, 6 by banding, 4 by ligation, 1 by embolization, and
      1 by distal ligation and bypass operation. Clinical characteristics of patients
      with hand ischemia included long-standing insulin-dependent diabetes (10),
      chronic hypertension (12), peripheral arterial disease (14; 93.3%), coronary
      artery disease (8), and systemic lupus erythematosis (1). Severe peripheral
      arterial diseases are commonly found and may be markers for risk of hand ischemia
      after access surgery.

PMID- 9536966
TI  - Thrombospondin-1 is elevated with both intimal hyperplasia and
      hypercholesterolemia.
AB  - BACKGROUND: Thrombospondin-1 (TSP-1) is important in platelet adhesion and
      aggregation, inflammation, cell to cell interaction, angiogenesis, and smooth
      muscle cell (SMC) proliferation. TSP-1 expression increases rapidly with injury.
      Therefore, we hypothesize that TSP-1 may play a role in the development of
      intimal hyperplasia (IH). The purpose of this study is to examine the interaction
      between cholesterol and TSP-1 on SMC proliferation and to quantitatively assess
      TSP-1 expression in an established model of IH, with and without underlying
      cholesterol-induced atherosclerosis. MATERIALS AND METHODS: In vitro, rabbit
      aortic SMC culture studies were performed to see the effect of TSP-1 antibodies
      on PDGF and, separately, cholesterol-induced SMC proliferation. In vivo, 23
      rabbits were fed either a regular or a high-cholesterol diet.
      Hypercholesterolemia was confirmed by measurement of serum levels. Subsets
      underwent intraluminal aortic injury. Aortas were harvested 8-10 weeks later.
      Arterial wall TSP-1 was evaluated immunohistochemically and quantified by
      computer image analysis. RESULTS: In vitro, TSP-1 antibodies were able to inhibit
      PDGF and cholesterol-induced SMC proliferation (P < 0.05). In vivo, TSP-1 was
      found predominantly in the extracellular matrix in the rabbit aorta. IH was
      uniformly seen status-post angioplasty. Hyperplasia was more prominent in samples
      from hypercholesterolemic animals. ANOVA and Student's t test analyses
      demonstrated significantly more TSP-1 in the high-cholesterol/angioplasty group
      than in all other groups (P = 0.0006 vs regular diet/no angioplasty group).
      CONCLUSIONS: These data are consistent with the hypothesis that TSP-1 contributes
      to the development of IH. This study suggests that injured arteries in
      hypercholesterolemic atherosclerotic rabbits overexpress TSP-1.

PMID- 9536967
TI  - Bacterial products primarily mediate fibroblast inhibition in biomaterial
      infection.
AB  - PURPOSE: The stimulation of fibroblast growth is essential for the normal healing
      and tissue integration of biomaterials. The local elevation of proinflammatory
      mediators in infected perigraft fluid (PGF) may inhibit this growth. We sought to
      determine whether infected PGF inhibited fibroblast growth, and, if so, whether
      this was primarily dependent on the biomaterial, bacteria, or host. METHODS: In
      vivo Dacron or expandable polytetra-fluoroethylene (ePTFE) grafts, sterile or
      colonized with slime-producing (RP-62A, viable or formalin-killed) or nonslime
      producing (RP-62NA) Staphylococcus epidermidis (1 x 10(7) CFU/cm2), were
      implanted in Swiss Webster mice, and the PGF was harvested at 7 and 28 days.
      Antibodies to tumor necrosis factor alpha, interleukin 1 alpha, interferon gamma
      (7 micrograms/day), and indomethacin (50 micrograms/day) were administered by
      microinfusion pumps for 7 days and the PGF was harvested. Inhibition of the
      proinflammatory mediators was confirmed by enzyme-linked immunosorbant assay. The
      nontreated, heat-treated, or trypsin-digested in vivo PGF was incubated with an
      in vitro [3H]thymidine murine fibroblast (ATCC CCL-12) proliferation assay.
      RESULTS: Fibroblast inhibition was significant at 7 and 28 days with infected PGF
      incubation compared with sterile and was not dependent on bacterial slime
      production or viability. Dacron sterile PGF did not significantly inhibit
      fibroblasts compared with control, whereas sterile ePTFE stimulated (P < 0.05)
      fibroblasts. Treatment of the PGF with proinflammatory cytokines, heat, and
      trypsin failed to reverse fibroblast inhibition in the infected state.
      CONCLUSION: Biomaterial infection is associated with fibroblast inhibition that
      is dependent primarily on bacterial products and not the host or biomaterial.
      Conservative intervention strategies for graft infection need to address the
      problem of poor healing as well as bacterial clearance.

PMID- 9536968
TI  - Process improvements reduce utilization of resources for aortic aneurysm repair.
AB  - In conjunction with the VA reorganization to promote greater efficiency of health
      care provision, ambulatory surgery (AS) programs have been created. These
      programs institute outpatient preoperative assessment and operative management.
      This study examines the impact of these process changes on resources utilized by
      patients requiring repair of abdominal aortic aneurysms (AAAs). The medical
      records of 15 consecutively treated patients undergoing elective, infrarenal AAA
      repair before (1992-1993) and after (1995-1996) AS implementation were reviewed.
      Resource utilization was assessed by evaluating preoperative tests performed
      (inpatient or outpatient), ICU days, and inpatient length of stay (LOS).
      Postoperative morbidity and mortality were noted. Patient age, AAA size, and
      prevalence of diabetes mellitus, hypertension, cardiac disease, COPD, and tobacco
      use were similar between the two groups. Abdominal ultrasound, CT scanning, and
      angiography were significantly more frequently performed on an outpatient basis
      after implementation of the AS program. The median preoperative LOS was reduced
      in the AS group (1 vs 6 days, P = 0.001, Student t test), resulting in a lower
      inpatient LOS (11 vs 16, P < 0.01, Student t test). All patients survived and the
      incidence of complications was similar between the groups. Hospital resource
      utilization was significantly decreased, largely by shifting preoperative
      assessment to the outpatient setting. This study illustrates that benefits of an
      ambulatory surgery program can be extended beyond facilitating outpatient
      operations and should result in decreased length of hospitalization for other
      major surgical procedures, such as abdominal aortic aneurysm repair.

PMID- 9536970
TI  - Endotoxin temporarily impairs canine colonic absorption of water and sodium.
AB  - Diarrhea is a common manifestation of sepsis. We hypothesized that endotoxin may
      impair colonic absorption of water and electrolytes, an effect which may be
      related to altered liquid transit in the colon. Five dogs underwent construction
      of 50-cm colonic Thiry-Vella fistulas (TVF). Following recovery, absorption
      studies were performed by perfusing the TVF with an isotonic solution at 2.9
      ml/min containing polyethylene glycol (5 g/L). Fasting and postprandial colonic
      absorption of water, electrolytes, and glucose were determined. Liquid transit
      was assessed by bolus of a nonabsorbable marker (PSP) instilled into the proximal
      end of the TVF. Following completion of the baseline studies, each dog was given
      a single dose of Escherichia coli lipopolysaccharide 200 micrograms/kg i.v. and
      the studies were repeated daily for the next 3 days. Following endotoxin bolus,
      colonic absorption of water and sodium were decreased during fasting, while
      postprandial colonic absorption of water was also decreased. Colonic absorption
      of water and sodium returned to baseline values on postendotoxin day 2. Colonic
      secretion of potassium was decreased on postendotoxin days 1 and 3 in both the
      fasting and the fed periods. Fasting and postprandial liquid transit was also
      rapid on postendotoxin day 1, which correlated with the decreased absorption seen
      on that day. Liquid transit returned to baseline values on postendotoxin day 2.
      We conclude that endotoxin temporarily impairs postprandial colonic absorption,
      which may be due to the rapid liquid transit that occurs. These effects may
      contribute to the diarrhea seen during and after septic episodes.

PMID- 9536969
TI  - The histologic characteristics of primary and restenotic carotid plaque.
AB  - BACKGROUND: Although smooth muscle cell proliferation is a prominent feature of
      restenosis in experimental models, the role of cellular proliferation in the
      initiation and progression of carotid restenosis is not well documented. METHODS:
      Between 1985 and 1995, 35 carotid endarterectomies (CEA) in 34 patients were
      performed for restenosis. Patient risk factors, cerebrovascular symptoms, and
      operative findings were recorded. Tissue specimens from 29 of these cases and 14
      original specimens from the same patient were examined by light microscopy (H&E,
      trichrome, elastochrome, and Alcian blue) and immunohistochemistry (alpha actin,
      CD 68, vWF, and proliferating nuclear cell antigen (PCNA)) in order to determine
      the morphologic characteristics and cellular proliferative activity of the
      plaque. RESULTS: Hemodynamically significant recurrent stenosis occurred in the
      29 patients (69% symptomatic) between 2 months and 30 years after their initial
      CEAs. Eleven of 29 (38%) lesions were removed early (< 3 years). Recurrent
      lesions were characterized based on their components as neointimal thickening,
      24% (7/29), neointimal thickening and atherosclerosis, 55% (16/29), or
      atherosclerotic, 21% (6/29). Nineteen of 29 (66%) plaques were complicated by
      mural thrombus or intraplaque hemorrhage. An inflammatory cell infiltrate
      consisting of macrophages and T lymphocytes was observed adjacent to areas of
      recurrent atherosclerosis and macrophages in regions of intimal thickening.
      Although infrequently present (generally 1-3% of cells) PCNA-positive cells were
      detected in 41% (12 of 29) of recurrent and 14% (2 of 14) of primary plaques. No
      PCNA-positive cells were detected in the remaining 67% (29 of 43) of specimens.
      There was no statistical difference in the number of PCNA-positive cells in early
      recurrent lesions compared to those recurring after 3 years (36% vs 44%). PCNA
      immunoreactivity when present was most commonly noted in macrophages associated
      with thrombus or atheroma rather than smooth muscle cells. CONCLUSIONS: Although
      evidence of cellular proliferation was observed in 40% of recurrent carotid
      endarterectomy lesions, the proliferation rate was low (1-3%) and unrelated to
      the time interval of recurrence. Proliferative activity was most pronounced in
      macrophages associated with intraplaque hemorrhage or atheroma. The contribution
      of inflammatory cells to the biologic behavior of restenotic lesions requires
      further investigation.

PMID- 9536972
TI  - Acute effects of bile acids on the pancreatic duct epithelium in vitro.
AB  - BACKGROUND: Acute pancreatitis is associated with passage of gallstones, although
      the mechanism(s) linking the two processes remains undefined. Bile reflux into
      the pancreatic duct could play a role but the experimental conditions often
      employed to induce pancreatitis rarely develop clinically. Here we examined
      whether low concentrations of bile affect ductal electrophysiology as an indirect
      measure of ductal epithelial integrity and function in vitro. METHODS: The main
      duct was dissected out of freshly harvested bovine pancreata, cut into 1- x 2-cm
      sections, placed in tissue culture for 48-72 h, then placed in Ussing chambers.
      Changes in tissue resistance (Rt) and short-circuit current (Isc) were monitored.
      The responses to forskolin and bile (taurodeoxycholic acid, TDCA) were examined
      separately and together. RESULTS: Forskolin (10 microM) produced a decrease in
      the Isc without a significant change in Rt, suggesting a secretory response,
      followed by a return to baseline. TDCA caused a similarly reversible decrease in
      the Isc at low doses, but a persistent drop at higher concentrations. A
      concurrent drop in Rt was noted at all TDCA concentrations, the duration of which
      correlated with dosage and degree of histological damage. Prior exposure to low
      (0.5 mM) doses of TDCA significantly blunted the response to subsequent forskolin
      challenge. CONCLUSIONS: Acute exposure to TDCA in vitro causes epithelial damage
      at levels lower than those normally used to induce experimental pancreatitis. At
      the lower concentrations, Rt returns to baseline rapidly, suggesting recovery
      (restitution) from epithelial damage but with a persistent loss of the response
      to forskolin. Reflux of minute amounts of bile into the pancreatic duct could
      play a significant role in the pathogenesis of gallstone pancreatitis by
      uncoupling the normal stimulus-secretion apparatus of the ductal system and
      breaking down the epithelial barrier.

PMID- 9536971
TI  - The nitric oxide precursor L-arginine reduces expression of hyaluronan synthase
      in experimental vein bypass grafts.
AB  - BACKGROUND: The success of vascular bypass procedures is limited by the
      development of intimal hyperplasia (IH). The nitric oxide (NO) precursor, L
      arginine (L-ARG) significantly reduces IH in both arteries and experimental vein
      grafts; however, the precise mechanism has yet to be elucidated. Hyaluronan
      synthase-1 (HAS-1) is one of the two enzymes believed to be responsible for
      making hyaluronan, a key component extracellular matrix composition. PURPOSE: To
      determine how L-ARG supplementation affects the gene expression of HAS-1 in
      experimental vein grafts. METHODS: Thirty-four male New Zealand white rabbits
      were divided into three groups: control (no operation, regular chow and water, n
      = 4); L-ARG supplemented (n = 15); and no L-ARG (n = 15). The latter two groups
      underwent a right interposition carotid bypass using jugular vein. Vein grafts
      were harvested at 7, 14, and 21 days after surgery. Ribonuclease protection
      assays were performed using 32P-labeled riboprobes for HAS-1 and 18S rRNA as an
      internal control and expressed as a ratio (HAS-1/rRNA). RESULTS: There was a
      significant rise in HAS-1 expression in the vein grafts 7 (1.57 +/- 0.5), 14 (0.7
      +/- 0.2), and 21 days (2.82 +/- 0.7) after grafting compared to control (0.14 +/-
      0.08) (P < 0.05). L-ARG-supplemented animals had a significant decrease in HAS-1
      expression at 21 days (0.65 +/- 0.1) compared to nonsupplemented vein grafts
      (2.82 +/- 0.7) (P < 0.02). CONCLUSIONS: These results demonstrate for the first
      time a significant rise in HAS expression in the early experimental vein grafts.
      Furthermore, L-ARG supplementation significantly diminishes the expression of HAS
      at 21 days. These results may represent a potential mechanism by which
      augmentation of the L-ARG/NO pathway inhibits IH in experimental vein grafts and
      may ultimately provide for improved therapeutic interventions in alleviating IH.

PMID- 9536973
TI  - Hepatic uptake of amino acids immediately after liver transplantation is well
      preserved despite altered plasma profiles.
AB  - BACKGROUND: The liver is one of the principal organs responsible for the uptake
      and release of amino acids in the body. The ability of the transplanted liver to
      clear plasma amino acids is associated with a functioning allograft. However,
      clinical assessment is limited by the inability to access the portal vein
      postoperatively. Therefore, using a porcine liver transplant model, we examined
      (1) the plasma levels of amino acids presented to the new hepatic allograft and
      (2) the capacity of the new allograft to clear these amino acids from the
      circulation. MATERIALS AND METHODS: Two groups of commercially bred pigs were
      studied: a control group (n = 8) underwent laparotomy and a transplanted group (n
      = 6) underwent orthotopic liver transplantation (LT) using veno-venous bypass.
      All pigs had catheters placed in the carotid artery and portal and hepatic veins
      and ultrasonic transit time flow probes placed around the hepatic artery and
      portal vein. Plasma profiles of 23 amino acids were analyzed by high-pressure
      liquid chromatography. Hepatic balances of amino acids, using arteriovenous
      difference techniques coupled with hepatic blood flows, were also analyzed on
      postoperative day 1. RESULTS: Neither portal vein blood flow (703 +/- 74 ml/min
      vs 666 +/- 82 ml/min) nor hepatic artery blood flow (322 +/- 43 ml/min vs 209 +/-
      59 ml/min) was significantly different between the control and the transplanted
      groups, respectively. The transplanted group had significantly increased plasma
      levels of alanine (135 +/- 13 mumol/l vs 382 +/- 72 mumol/l), hydroxyproline (30
      +/- 5 mumol/l vs 60 +/- 9 mumol/l), methionine (25 +/- 2 mumol/l vs 55 +/- 10
      mumol/l), ornithine (36 +/- 5 mumol/l vs 141 +/- 33 mumol/l), phenylalanine (84
      +/- 5 mumol/l vs 120 +/- 12 mumol/l), threonine (75 +/- 9 mumol/l vs 159 +/- 27
      mumol/l), and tryptophan (17 +/- 2 mumol/l vs 31 +/- 4 mumol/l). The transplanted
      group also had significantly decreased plasma levels of isoleucine (122 +/- 12
      mumol/l vs 85 +/- 8 mumol/l) and taurine (71 +/- 7 mumol/l vs 35 +/- 7 mumol/l).
      These individual amino acid changes were not accompanied by impairment in the net
      hepatic amino acid balance or the hepatic fractional extraction of amino acids
      between the two groups. CONCLUSION: These results suggest that the circumstances
      associated with liver transplantation alter the fasting amino acid profile
      immediately postoperatively. However, liver transplantation does not impair the
      normal hepatic allograft uptake of most plasma amino acids. Thus, the changes
      observed in the circulating levels of amino acids may represent alterations in
      nonhepatic production and/or utilization. Furthermore, altered plasma amino acid
      profiles following liver transplantation are not necessarily indicative of
      impaired hepatic allograft amino acid metabolism.

PMID- 9536974
TI  - Local treatment of prosthetic vascular graft infection with multivesicular
      liposome-encapsulated amikacin.
AB  - BACKGROUND: Contaminated surgical fields limit the use of prosthetic vascular
      grafts. We studied the efficacy of sustained-release amikacin applied locally to
      contaminated grafts in the prevention of infectious complications. MATERIALS AND
      METHODS: Thirty-one New Zealand white rabbits underwent placement of a
      polytetrafluoroethylene (PTFE) interposition graft in a 1-cm segment of the
      descending aorta. The surgical field was infected with application of 10(5) to
      10(8) Staphylococcus aureus organisms suspended in normal saline solution.
      Nineteen rabbits underwent contaminated aortic graft placement without treatment.
      Twelve rabbits were treated with local application of 2.5 ml of amikacin
      encapsulated in lipid particle-based sustained-release dosage form. Rabbits were
      observed for 2 weeks and then evaluated for the presence of graft infection.
      RESULTS: Seventy-five percent of the treated rabbits survived without evidence of
      graft infection or systemic sepsis versus 37% in the untreated group (P < 0.04).
      Cultures verified the absence of organisms in all surviving rabbits without
      clinical infection. CONCLUSIONS: Sustained-release lipid particle-encapsulated
      amikacin applied to contaminated PTFE grafts increased survival and decreased
      postoperative graft infections. Adjunctive use of local, delayed-release
      antibiotics in contaminated vascular beds may allow wider clinical use of
      prosthetic grafts.

PMID- 9536975
TI  - Elevated cutaneous leukocyte concentration in a rodent model of acute venous
      hypertension.
AB  - BACKGROUND: The pathophysiologic mechanism of the skin pathology in chronic
      venous insufficiency is venous hypertension (VHTN). Microvascular dysfunction
      involving leukocytes has recently been proposed as the primary mediator of tissue
      damage from VHTN. We developed a rodent model allowing the investigation of the
      effects of acute VHTN on tissue leukocyte concentration. MATERIALS AND METHODS:
      Under general anesthesia, adult male rats underwent transperitoneal isolation of
      the inferior vena cava and the common iliac veins and arteries. Bilateral thigh
      incisions allowed isolation of the common femoral veins and superficial
      epigastric veins (SEV: distal branch of the femoral vein in the thigh). Pressure
      in the SEV and flow in the iliac artery were measured before (T-Pre), immediately
      after (T-0), and for 135 min (T-1) after ligation of the cava, iliac, and femoral
      veins. Sham rats were identical except no venous ligation was performed. After
      the T-1 pressures were obtained, the distal hindlimb and forelimb skin was
      harvested and processed to measure myeloperoxidase (MPO) activity, an index of
      the number of tissue leukocytes. To evaluate the effect of arterial flow
      reduction known to occur with acute venous ligation, the above measurements were
      made in an Aortic group of rats in which the aorta was manually stenosed.
      RESULTS: This venous ligation technique resulted in a significant (P < 0.05) and
      sustained rise in venous pressure (T-Pre, 9.91 +/- 0.94 and T-1, 26.22 +/- 2.15).
      Hypertensive rats had significantly elevated hindlimb MPO activity (4.77 +/-
      0.36) vs forelimb (0.60 +/- 0.39), Sham (hindlimb, 0.77 +/- 0.41; forelimb, 0.10
      +/- 0.05), and Aortic (hindlimb, 0.96 +/- 0.38; forelimb, 0.58 +/- 0.11)
      controls. CONCLUSIONS: Acute VHTN was successfully created by venous ligation in
      this newly developed rat model. VHTN, but not arterial flow reduction, was
      associated with significantly elevated hindlimb skin MPO activity, suggesting
      that leukocytes may indeed be mediators of skin pathology in VHTN. This model
      will allow further investigation into the mechanisms of microvascular dysfunction
      in VHTN.

PMID- 9536976
TI  - Lipopolysaccharide protects polymorphonuclear leukocytes from apoptosis via
      tyrosine phosphorylation-dependent signal transduction pathways.
AB  - BACKGROUND: The present study was undertaken to determine if tyrosine
      phosphorylation signal transduction pathways, which are known to be activated in
      polymorphonuclear leukocytes (PMN) by lipopolysaccharide (LPS), play a role in
      priming of PMN oxidative burst and protection of PMN from apoptosis by LPS, and
      to determine if an interface between these two signaling pathways exists.
      METHODS: PMN were combined with or without 10-fold serial dilutions (0.1 ng-1
      microgram/ml) of LPS and incubated at 37 degrees C/5% CO2. After 24 h PMN
      apoptosis was assessed using fluorescence microscopy and DNA agarose gel
      electrophoresis. Additional PMN were pretreated with the tyrosine kinase
      inhibitors genistein and herbamycin A before addition of LPS. Tyrosine
      phosphorylation was detected by immunoblotting. Oxidant production was
      quantitated by following the oxidation of a chromophore to its fluorescent
      product. RESULTS: LPS delayed the onset of apoptosis and prolonged the survival
      of PMN in a dose-dependent fashion. Both tyrosine kinase inhibitors blocked the
      protective effect of LPS on PMN apoptosis; however, only genistein blocked the
      priming effect of LPS on PMN oxidative burst. CONCLUSIONS: Tyrosine
      phosphorylation signal transduction pathways are central to protection of PMN
      from apoptosis by LPS. Although tyrosine phosphorylation pathways also play a
      role in priming of the oxidative burst in PMN, our data suggest that there is not
      an interface between these important signaling pathways.

PMID- 9536977
TI  - Immediate and long-term portal hemodynamic consequences of small-diameter H-graft
      portacaval shunt.
AB  - BACKGROUND: Effective hepatic blood flow is thought to play a critical role in
      outcome following portal decompressive procedures. We have shown previously that
      hepatic arterialization occurs soon after shunting, preserving nutrient flow, but
      the remote effects of shunting are unknown. The purpose of this study was to
      determine the effect of small-diameter prosthetic H-graft portacaval shunt
      (HGPCS) on effective hepatic blood flow (EHF) and portal pressures 1 year from
      shunt placement. METHODS: Patients undergoing 8-mm HGPCS had effective hepatic
      blood flow determined using low-dose galactose clearance preoperatively,
      postoperatively, and at 1 year postshunt. Portal blood flow, pressures, and
      portal vein/inferior vena cava pressure gradients were determined
      intraoperatively before and after shunt placement and at 1 year. RESULTS: Twenty
      patients undergoing shunting had flows measured. All patients had significant
      reductions in portal vein/inferior vena cava pressure gradients while effective
      hepatic flow was maintained immediately postoperatively. At 1 year following
      shunting, effective hepatic blood flow was significantly lower than both pre- and
      postoperative rates of flow while portal pressures and gradients were
      significantly increased. Albumin, cholesterol, and PT were improved at 1 year
      while total bilirubin was slightly worse. Nineteen of 20 patients are still alive
      with average follow-up of 26 +/- 10.3 months. Four patients were encephalopathic
      preop, 5 postop, and none chronically. CONCLUSIONS: Recollateralization of
      varices and progression of cirrhosis may account for the observed reductions in
      EHF at 1 year. Regardless of the cause, diminution of EHF at 1 year is well
      compensated as demonstrated by minimal encephalopathy and ascites, improved
      hepatic function reflected in blood chemistry profiles, and good survival.

PMID- 9536978
TI  - Proteoglycan gene expression is decreased in abdominal aortic aneurysms.
AB  - BACKGROUND: Abdominal aortic aneurysms (AAA) are characterized by both increases
      in proteolysis and changes in the biosynthesis of the extracellular matrix (ECM)
      proteins. Proteoglycans are important components of the ECM, particularly the
      small proteoglycans, biglycan and decorin. Biglycan and decorin regulate cell
      proliferation and collagen assembly. Therefore, the purpose of this study is to
      quantify the levels of mRNA for biglycan and decorin in normal aorta (Na) and
      AAA. MATERIALS AND METHODS: Northern blot hybridization and competitive
      polymerase chain reaction using gene-specific external standards were used to
      quantify mRNA levels of bigylcan and decorin in RNA derived from AAA and NA.
      Results are expressed as a percentage of glyceraldehyde-3-phosphate dehydrogenase
      or normalized to ribosomal RNA content and compared using the unpaired t test.
      RESULTS: A statistically significant 15-fold decrease in biglycan mRNA expression
      was observed in AAA compared to NA (176.9% vs 11.8%, P < 0.001). In contrast to
      biglycan, the decorin mRNA expression is unchanged in AAA compared to NA.
      CONCLUSIONS: The marked decrease in biglycan mRNA levels is unique to aneurysmal
      disease of the aorta. In atherosclerosis and restenosis, biglycan expression is
      increased in comparison with normal artery. This decrease in biglycan expression
      may reflect important regulatory changes specific for the AAA. Furthermore, a
      decrease in biglycan gene expression and biosynthesis could have a broad impact
      on the physiology and matrix architecture of the aorta.

PMID- 9536979
TI  - Inflammation and a thickened mucus layer in mice with cholesterol gallstones.
AB  - BACKGROUND: Based on previous work which suggested that biliary crystals may
      induce inflammation in the gallbladder wall and that inflammation is an early
      event during the formation of pigment gallstones in the dog, studies were
      performed examining mucus layer thickness, myeloperoxidase activity, and
      interleukin-1 (IL-1) activity in the wall of mouse gallbladder during formation
      and growth of cholesterol gallstones. METHODS AND MATERIALS: The inflammatory
      effects of cholesterol gallstones at 2 and 4 weeks were studied in BalB/C mice
      fed a crushed standard mouse chow with added cholesterol (1.0%) and cholic acid
      (0.5%). Results were compared to those of normal mice fed standard mouse chow.
      The presence or absence of crystals and stones was determined by gross and
      microscopic examination of bile. Myeloperoxidase and IL-1 activity in the
      gallbladder wall was measured using well-established bioassays. Mucus layer
      thickness was measured by darkfield microscopy. RESULTS: All mice fed a
      lithogenic, 1.0% cholesterol/0.5% cholic acid diet developed cholesterol crystals
      and gallstones at 2 and 6 weeks. No control mice developed either crystals or
      gallstones. Myeloperoxidase and IL-1 activities, markers of an inflammatory
      response, increased significantly in the gallbladder of mice with crystals at 2
      weeks. Myeloperoxidase activity increased two- to three-fold, and IL-1 activity
      sevenfold, by 6 weeks. Mucus layer thickness also progressively increased during
      the 6-week period. CONCLUSIONS: It is concluded that inflammation is an early
      event associated with the appearance of crystals and gallstones in bile.

PMID- 9536980
TI  - Effects of mesenteric ischemia and reperfusion on small bowel electrical
      activity.
AB  - Previous studies involving basic electrical rhythm (BER) have not been carried
      out far enough to fully characterize the relationship between mesenteric ischemia
      and BER. The phenomenon of reperfusion injury has also not been correlated with
      BER activity. The goal of this study was to characterize changes in BER during
      mesenteric ischemia and reperfusion and to correlate them with changes in
      pathology. METHODS: Serosal electrodes were used to record the electrical
      activity of rabbit jejunum (n = 20) at baseline, during ischemia (90-210 min),
      and during reperfusion (120-240 min). BER frequency and amplitude were monitored,
      and biopsies were taken at the end of ischemia and reperfusion. A pathologist
      blinded to the specimen identity graded the histology on a scale of 0 (no
      changes) to 6 (transmural necrosis). Paired t test, the Kruskal-Wallis test of
      non-parametric ranks, and Fisher's r to z test were used for statistical
      significance where appropriate. RESULTS: BER frequency and amplitude fell
      significantly after 15 min of ischemia and became undetectable by 90 min of
      ischemia in all animals. The likelihood that BER would return during reperfusion
      was highly correlated with length of ischemia (r = 0.99). Longer periods of
      reperfusion were associated with increasing pathologic grade. CONCLUSIONS: BER
      frequency and amplitude are very sensitive to ischemia and their changes occur
      well before histopathologic changes. The variation in electrical activity of the
      small bowel during ischemia and reperfusion is a dynamic process that reflects
      the metabolic state of the smooth muscle. If electrical activity of the bowel is
      to be used for assessment of viability, continuous recordings more accurately
      reflect the metabolic state of the smooth muscle.

PMID- 9536982
TI  - [Relationships between p53 induction, cell cycle arrest and survival of normal
      human fibroblasts following DNA damage].
AB  - It is now well established that in response to genotoxic stresses mammalian cells
      show an increased p53 protein levels and undergo cell cycle arrest at G1/S and
      G2/M checkpoints. But, the consequences of these cell cycle arrests on cell
      survival are not yet elucidated. In this study, we have analysed the
      relationships between p53 protein induction, cell cycle arrest and cell survival
      following exposure of normal human fibroblasts (NHFs) to various genotoxic agents
      such as cisplatin, UV radiation and gamma radiation. p53 protein accumulation and
      G2/M arrest arose at the same time following exposure to DNA damaging agents,
      suggesting that p53 is responsible for the G2/M block. However, following
      inhibition of p53 induction by an antisense oligonucleotide, this G2/M arrest is
      even more important and correlates with an enhanced sensitivity of NHFs to UV
      radiation. In addition, there appears to be a threshold in the response of NHFs
      to DNA damaging agents, p53 induction and cell cycle arrest being observed only
      with lethal UV doses. We show that: 1) there appears to be a threshold in the
      cellular response to genotoxic agents, below which neither p53 induction, nor
      cell cycle arrest, nor cell survival alteration occur and beyond which p53
      induction is accompanied by cell cycle arrest and decreased cell survival; 2)
      although there is a tight temporal relationship, the onset of which depends of
      the DNA damaging agent used, between the start of p53 induction and the
      occurrence of G2/M arrest, this latter is independent of p53; 3) p53 inhibition
      enhances NHFs' sensitivity to DNA damaging agents, the extent of the G2/M arrest
      correlating with decreased cell survival. Finally, the lack of obligatory
      correlation between p53 inactivation, apoptosis and radio- or chemoresistance is
      discussed.

PMID- 9536981
TI  - Prospective double-arm study of fibrinolysis in surgical patients.
AB  - BACKGROUND: During surgery, the balance between thrombosis and fibrinolysis is
      altered. Methods reported to increase fibrinolysis, such as compression devices,
      may reduce venous thrombosis. However, there are no prospective studies comparing
      methods and the effect on fibrinolysis. MATERIALS AND METHODS: In a prospective
      study, general surgical patients were randomized to either sequential compression
      devices (Group 1) or subcutaneous heparin (Group 2), and fibrinolysis factors
      were measured in order to determine the effect on the fibrinolysis system. Blood
      samples were drawn at a similar time of the day with the tourniquet off.
      Specifically, t-PA antigen, plasminogen activator inhibitor-1 (PAI-1), and D
      dimer were measured preoperatively (preop) and on Postoperative Days (POD) 1 and
      7 by the ELISA method. Fibrinolysis factors were reported as the mean +/- SD and
      as percentage change from preoperative values. Noninvasive vascular studies were
      performed preop, and on POD 1, 7, and 30, by an examination of the infrainguinal
      venous system and external iliac veins in bilateral lower extremities.
      Nonambulatory patients were excluded from the study and DVT prophylaxis methods
      were initiated at surgery and used through POD 2. RESULTS: For the 136 patients
      in the study, there were no differences in clinical characteristics such as age,
      surgical time (all > 60 min), anesthesia type (general or spinal), type of
      surgical procedure, or other risk factors for DVT. Two DVTs occurred at POD 1 and
      30 (both Group 2), and one pulmonary embolism in each group (POD 7 for Group 1;
      POD 1 for Group 2). For subjects without thrombosis, D-dimer changes were
      parallel for both groups, increasing through POD 7. Similarly, t-PA antigen
      levels rose from baseline on POD 1 in both groups, with a return toward baseline
      by POD 7. The PAI-1 levels increased on POD 1 in both groups, but severalfold
      more in Group 1 (compression devices). The elevation in PAI-1 decreased by 50% in
      Group 1 by POD 7, while values returned to normal in Group 2. These changes were
      not significant using the Mann-Whitney test. Only three patients had thrombotic
      episodes so that data on changes in fibrinolysis factors are difficult to compare
      with the larger group. CONCLUSIONS: This is the first report of a prospective,
      randomized comparison of fibrinolysis factors using sequential compression
      devices in comparison to low dose unfractionated heparin in general surgical
      patients, and comparing postoperative values to preop. Both groups showed an
      enhanced fibrinolysis by elevation in t-PA antigen and D-dimer on POD 1, as
      expected when fibrinolysis occurs. While PAI-1 and t-PA work in parallel, the
      marked elevation of PAI-1 on POD 1 (although only slightly above reference
      values) and continuing into POD 7 for subjects using compression devices requires
      further inquiry. The elevation of PAI-1 in the face of elevated t-PA and D-dimer
      has been reported, but the comparison between patients using sequential
      compression devices and mini-dose heparin has not been reported. The reason for
      the elevation requires additional study into other influences on the synthesis,
      secretion, and/or function of PAI-1 that do not affect t-PA.

PMID- 9536983
TI  - [Interactions between biospecific polymers and MCF7 cells: modulation of cellular
      proliferation and expression of estrogen receptors].
AB  - Numerous studies on interactions between insoluble polymers and cell membrane
      receptors indicated modulation of cellular proliferation and cell phenotype by
      these polymers considered as biospecific. We synthesized several biospecific
      polymers in order to investigate the interactions between polymers and
      intracellular receptors as estrogen receptors considered as tumoral indicator of
      breast cancer. Biospecific polymers were obtained by random substitutions of
      crosslinked polystyrene beads with suitable chemical groups (sulfonate and amino
      acid sulfamides). These polymers were used as microcarriers for culture of MCF7
      cells, a cellular model of human breast cancer. Quantification of MCF7 cell
      estrogen receptors was determined by radioligand binding assay for different days
      of cellular proliferation. The data obtained with MCF7 cells cultured on
      biospecific polymers show an inverse relationship between polymer induced
      inhibition of cell proliferation and polymer induced increase of estrogen
      receptors. Similar inverse relationship was obtained with MCF7 cell cultured on
      standard polystyrene tissue culture plates. The various interaction between
      insoluble polymers and MCF7 cells could be related to the proportion and the
      nature of the substitutive chemical groups. These biospecific polymers could
      presents sites of interaction with cell membrane receptors leading to modulation
      of cell biological activity. The different insoluble polymers were used as
      preliminary models: a practical application could be a methodology of cellular
      selection using soluble biospecific polymers (for example chemically modified
      dextrans).

PMID- 9536984
TI  - [Cancer incidence among active female workers at Electricite de France-Gaz de
      France].
AB  - Our aim was to draw up a first general view of cancer pathology among the EDF-GDF
      women thanks to the cancer register among active employees created by the social
      security department of the French national electric and gas company EDF-GDF.
      Between 1978 and 1992, 764 cases of cancer were diagnosed. Breast cancer was the
      most common (52.4%), followed by gynaecological cancers: uterus (8.6%) and ovary
      (6.2%), and colon and rectum cancers (5.4%). The age-standardized breast cancer
      incidence using the 1978-1982 period as a basis increased over time. A higher
      incidence for breast cancer and a lower incidence for uterus cancer were observed
      among the EDF-GDF women during the 1978-1982 and 1983-1987 periods, compared to
      French women of same age. The study of the relationship between breast cancer
      risk and socioeconomic status, by means of indirect standardization, showed that
      the breast cancer risk increased with increasing socioeconomic status. Thus
      manual workers had a lower breast cancer risk than the EDF-GDF woman cohort (SIR
      = 0.72), foremen had the same risk (SIR = 1.05) and managers had a significantly
      higher risk (SIR = 1.64). Moreover a case-control study showed that the change in
      socioeconomic status between the beginning (20 years old) and the middle of a
      career (35 years old) was important but it was essentially the socioeconomic
      status at the beginning which determined the breast cancer risk. The results
      support the hypothesis of a "social class" effect through risk factors during the
      first part of the life.

PMID- 9536985
TI  - [Evaluation of the diagnostic usefulness of CA125 immunoscintigraphy for ovarian
      carcinoma follow-up after treatment: contribution of this technique in Grenoble
      University Medical Center].
AB  - Immunoscintigraphy using indium-111-labeled OC125 monoclonal antibody F(ab')2
      fragments is a technic complementary of morphological imaging (i.e.
      ultrasonography and computed tomography). It allows early detection of
      recurrences of ovarian carcinomas. We performed immunoscintigraphy 30 times in 26
      patients who previously underwent radical treatment for ovarian carcinoma, and
      were suspected to have a recurrence. Our purposes were appreciation of diagnostic
      accuracy of the method, and above all its impact on clinical decisions and
      evolution of the patients. There were, after reevaluation of the results, 18 true
      positives, 7 true negatives, 3 false negatives and 2 false positive cases
      (sensitivity 85.7%, specificity 77.8%). Bayesian analysis showed positive and
      negative predictive values of 86% and 87% when probability of recurrence a priori
      was 50%, and 80% and 58% when probability of recurrence a priori was 70%. The
      result of immunoscintigraphy contributed to clinical decisions in 24 cases out of
      30, and led to a correct decision for the patient in 21 cases. Conversely, for
      the 6 cases in which the result has not been considered, to take this result into
      account would have been beneficial in 4 cases, but harmful in 2. Finally,
      survival tended to be longer when immunoscintigraphy was negative, which could be
      associated with a better prognosis. We conclude that OC125-immunoscintigraphy may
      be useful for ovarian carcinoma follow-up and may contribute to a better
      therapeutic strategy.

PMID- 9536986
TI  - [Gene therapy of a model of glioblastoma in rats using adenovirus vector encoding
      the HSVtk gene].
AB  - Our aim was to test the therapeutic effects of adenovirus-mediated gene therapy
      in an animal model of brain tumor which was obtained by injection of 9L
      gliosarcoma cells into the caudate nucleus of rat brains. Seven days after the
      implantation of tumor cells, adenovirus vectors bearing the Escherichia coli beta
      galactosidase gene (ADV beta-gal) or the herpes simplex virus thymidine kinase
      gene (ADVtk) were stereotactically injected in the tumor. Injection of the ADV
      beta gal resulted in the expression of the marker gene in 61% of the animals.
      Transfer of the ADVtk was followed, 3 days later, by intraperitoneal injection of
      ganciclovir (GCV) for 10 days. A control group was treated with saline instead of
      GCV. We observed a significant regression of the tumors in 50% of the rats
      treated with ADVtk and GCV as compared with control animals. In 4 cases out of 6,
      the tumor completely disappeared after treatment. These results demonstrate the
      potential efficacy of adenovirus-mediated transfer of the HSVtk gene following by
      GCV administration for the treatment of glioblastomas.

PMID- 9536987
TI  - [Current data on the role of APC protein in the origin of colorectal cancer].
AB  - The adenomatous polyposis coli (APC) gene has been found to be mutated during the
      development of sporadic colorectal cancers as well as in familial adenomatous
      polyposis (FAP). These conditions result from initially somatic and germ line
      mutations respectively. In both cases, the expressed protein is truncated at its
      carboxyterminal region. Investigations into the role of wild-type APC have led to
      a better understanding of the importance of mutations in the genesis and
      progression of adenomas. APC was shown to regulate cell growth and cell death, to
      bind beta-catenin, and to colocalize with microtubules. APC truncation was
      therefore hypothesized to alter cell multiplication and cells are no longer able
      to undergo apoptosis. Owing to its beta-catenin binding, APC can modify the pool
      of beta-catenin which is in part utilized in the assembly of adherens junctions
      and in nuclear signalling. Truncated APC is unable to regulate this pool thereby
      altering adhesion and cell signalling. Finally, APC involvement in microtubule
      dependent locomotion may explain some changes in cell movement which are observed
      in adenomas. The establishment of murine mutants and of normal and malignant
      intestinal cell cultures have allowed to assess biochemical and physiological
      properties of APC and its putative role in the genesis of colorectal
      carcinogenesis. Moreover, these experimental models have suggested a variety of
      possible therapeutic approaches.

PMID- 9536988
TI  - [What's new about microsatellite instability significance in human
      carcinogenesis?].
AB  - Microsatellite instabilities (MIN) represent a new type of mutation characterized
      by genomic instability (or replication error phenotype, RER+). First identified
      in sporadic and familial colorectal tumors, the RER+ phenotype has been sought in
      multiple types of cancers. Thus, two types of instability mechanisms have been
      shown: one due to inactivation of the mismatch repair system (phenotype RER+) and
      a second still unclear (instability of tri- and tetra-nucleotide repeats). In
      both cases, MIN seem to be the reflect of a new tumorigenesis pathway. In the
      context of mismatch repair defect, numerous observations show that, although
      instabilities seem to be random, they play a direct role in the tumoral process
      by altering genes that control cell growth and apoptosis. Today, MIN, as well as
      the detection of mutations in the DNA mismatch repair genes, can be used as
      diagnosis tools in oncology and provide usefull indications to adapt the
      chemotherapy to the disease.

PMID- 9536989
TI  - [Stereotaxic fine-needle aspirations of clinically latent breast cysts: an
      efficient and neat procedure].
AB  - The purpose was to evaluate the interest of stereotaxic fine-needle aspiration
      for round opacities when the ultrasound and echoguided punctures are inefficient;
      especially when women are under menopausal hormonal replacement therapy. Sixty
      stereotactic guided fine-needle aspirations detected by mammography have been
      performed between january 1990 and august 1996. The stereotaxic procedure is
      performed with a DMR unit (GE with Stereotix II). Stereotaxic views are done to
      verify needle position. After aspiration, cytologic examination is realised.
      Cystic fluid was always obtained and cytologic examination proved benign cysts in
      all cases. In 50 cases, cysts completely disappeared. There were 2 relapses that
      received after a second. This method is reliable for evaluation of non palpable
      mammographically detected opacities. The use of this technique spares the patient
      a surgical biopsy. This procedure enables women under menopausal hormone
      replacement therapy to continue the treatment.

PMID- 9536990
TI  - [Angiopoietin-2, a new molecular actor involved in vascular tree morphogenesis].
AB  - Angiopoietin-2 is a new member of the family of the ligands of Tek (Tie2), a
      transmembrane receptor with tyrosine kinase activity which is specifically
      expressed in endothelial cells during angiogenesis. Several lines of evidence
      indicate that angiopoietin-1 is involved in pericyte recruitment by endothelial
      cells and in the maintenance of cell-cell and cell matrix association in mature
      capillaries. Angiopoietin-2 behaves as an antagonist of angiopoietin-1. It is
      suggested that it looses capillary structure and renders endothelial cells to
      become responsive to angiogenic stimuli.

PMID- 9536991
TI  - [P73: a kin to the p52 tumor suppressor gene].
AB  - A gene with remarkable sequence homology with the tumour suppressor gene p53 is
      located at the tip of the short arm of human chromosome 1 which is often found to
      be deleted in neuroblastomas, melanomas and breast cancers. Despite their
      structural and functional similarities, p53 and p73 may have distinct roles in
      cell grow regulation.

PMID- 9536992
TI  - [Analysis of patients' perception of their stay in a medical intensive care unit.
      Les trois equipes d'infirmieres].
AB  - OBJECTIVES: Evaluate patients' appraisal of their stay in a medical intensive
      care unit and analyze their anxiety. PATIENTS AND METHODS: Two 5-month
      prospective studies with specific questionnaires were filled out by patients with
      the help of a psychologist. The first study (61 patients) evaluated global
      appraisal of the stay and the second study (53 patients) focused on anxiety using
      questionnaires also filled out by nurses. RESULTS: The study population was not
      different from the global population admitted to intensive care during the same
      period. The patients felt secure in 97% of the cases but suffered pain (53%),
      insomnia (62%), discomfort due to noise (49%) or light (37%), and expressed
      anxiety (55%). The second study confirmed the anxiety in 61% of the patients.
      Using surrogate markers of anxiety, the psychologist judged that anxiety was
      underestimated in 20% of the cases. In 17%, anxiety was expressed by patients but
      not felt to be present by nurses. DISCUSSION: In order to decrease the anxiety of
      patients admitted to a medical intensive care unit, every effort should be made
      to lessen pain and unnecessary discomfort. All personnel working in the unit
      should be able to recognize the patients' anxiety.

PMID- 9536993
TI  - [Can medical files be used to audit hospital health care? Results of a regional
      audit of hospital file quality].
AB  - OBJECTIVES: The clinical audit method based on a retrospective analysis of
      medical files can be used to assess hospital health care. The reliability of the
      results obtained depends on the validity of the data in the file and its
      completeness. The aim of this work was to assess the quality of this information
      source. METHODS: The simplified ANDEM/ANAES from was proposed to 47 medical
      information departments of public and private hospitals participating in the
      public health care service in the Provence-Alples-Cote d'Azur region. The audit
      was conducted on a sample of hospital stays during a regular 6-month quality
      control assessment of hospital health care activity. RESULTS: Analysis of the 467
      forms returned by 39 hospitals, showed that the quality of medical file
      recordings should be improved as a large amount of data or important documents
      were missing: reason for hospitalization (recorded on 74.1% of files), operation
      report (found in 83.2% of files) and discharge summary (found in 66.6% of files).
      CONCLUSION: Clinical audits would be compromised in certain hospitals by the use
      of medical files. Efforts to improve the quality of hospital medical files should
      be a priority.

PMID- 9536994
TI  - [Differentiated thyroid carcinomas manifesting as toxic adenoma].
AB  - BACKGROUND: Hot thyroid nodules are generally benign. We report two exceptional
      cases of thyroid carcinomas mimicking toxic adenomas. CASE REPORTS: A 35-year-old
      man and a 55-year-old woman had thyroid carcinoma behaving as an autonomously
      hyperfunctioning nodule. DISCUSSION: Only twenty similar cases have been reported
      in the literature. While a hot nodule on radio-iodine scan is unlikely to be
      malignant, the possibility of carcinoma should not be overlooked. Surgery should
      therefore be the preferred treatment of toxic adenoma.

PMID- 9536995
TI  - [Large cervical hematoma of parathyroid origin].

PMID- 9536996
TI  - [Gastric site of epidermoid carcinoma].

PMID- 9536997
TI  - [Effect of dexamethasone on Doppler velocimetries of the fetal cerebral
      arteries].

PMID- 9536998
TI  - [Vaccination against influenza in diabetics: survey at the end of winter 1996
      97].

PMID- 9536999
TI  - [Eulogy of wine?].
AB  - In the literature the beneficial effects on health of drinking alcoholic
      beverages, especially red wine, is becoming increasingly more evident. We report
      an objective analysis of the advantages and the dangers of such a tendency. It
      appears that the daily consumption of red wine at moderate doses (200-400 ml a
      day) has real prophylactic effects. These are particularly marked in the
      prevention of coronary heart disease (CHD), but also for a possible cancer
      chemopreventive activity, in the prevention of type II diabetes, of ischemic
      stroke, of osteoporosis in older women, and of Alzheimer's disease. But, inasmuch
      as the consumption of alcoholic beverages always involves a potential danger
      (organic diseases, risk of dependence, alcoholism), from a medical point of view
      eulogy to wine is ethically indefensible. Similar effects may be obtained from a
      diet rich in fruits and fresh vegetables.

PMID- 9537000
TI  - [Practical management of community-acquired pneumonia].

PMID- 9537001
TI  - [Genetic predispositions to breast cancer].
AB  - NEW DATA: Genetic epidemiology and position cloning techniques have made it
      possible to estimate the risk women with a family history of breast cancer have
      of developing a breast tumor. THREE PREDISPOSITION GENES: Three BReast CAncer
      genes (BRCA1, BRCA2 and BRCA3) have been localized on chromosomes 17 13 and 8. It
      is highly likely that other genes also have an influence. GENETIC TESTING: When
      an altered BRCA1 or BRCA2 gene is identified in a family, a gene test can be
      proposed to recognize predisposition in relatives. A negative test means the
      subject is not predisposed to breast cancer and that transmission to offspring is
      not possible. Inversely, the risk of breast cancer is high if the mutation is
      detected, raising the difficult problem of counselling, particularly in young
      subjects. PROBLEMS RELATED TO SCREENING TESTS: Screening tests can only be
      undertaken if the "candidate" is aware of the consequences of the screening
      results and has had enough time to make a fully informed decision.
      Confidentiality must be particularly strict, particularly in the field of
      employment and insurance.

PMID- 9537002
TI  - [Renal effects of AT1 angiotensin receptor antagonists (AT1ra)].
AB  - RENIN-ANGIOTENSIN ANTAGONISTS: The renal effects of angiotensin II receptor
      antagonists (AT1 blockers) can be compared with another class of drugs inhibiting
      the renin-angiotensin-aldosterone system, i.e. the angiotensin I converting
      enzyme inhibitors (ACE1). SIMILAR BUT SPECIFIC EFFECTS: The renal effects of
      these two classes of drugs are similar but each class has specific effects
      explained by several mechanisms. i) The system includes a large number of active
      peptides (angiotensin II, angiotensin III, angiotensin 1-7) which exert various
      effects according to their specific receptor(s): ii) several types of angiotensin
      II receptors have been identified (AT1, AT2, AT4 ...). Only AT1 blockers are
      available in clinical practice. iii) Receptor or enzyme blockade can produce
      varying effects; ACE inhibition is not specific since increased bradykinin
      activity is associated with the suppression of angiotensin peptide generation.
      EXPERIMENTAL AND CLINICAL TRIALS: Experimental and recent clinical studies have
      shown that AT1 blockers can induce, like ACE1, hypotension, renal vasodilation
      and natriuresis. The definite effects on discrete renal structures (vessels,
      glomeruli, tubules) differ however in magnitude which may suggest specific
      indications according to the pathophysiological background (renal disease,
      congestive heart failure, etc.).

PMID- 9537003
TI  - [Histiocytic cytophagic panniculitis].
AB  - A HISTOPATHOLOGICAL DIAGNOSIS: Histiocytic cytophagic panniculitis is the
      specific skin finding in the reactive hemophagocytic syndrome. It is a feverish
      nodular eruption which accompanies the other clinical and biological features of
      the reactive hemophagocytic syndrome. Histopathologic changes are diagnostic and
      consist in a lobular panniculitis characterized by the presence of a histiocytic
      infiltration of the fat. Histiocytes are benign in appearance and show variable
      degree of phagocytosis. INFECTION AND IMMUNE ANOMALIES: In more than 50% of the
      cases, the disease is triggered by an infection (mainly a viral infection from
      the herpes-virus family) in a patient with altered immune function
      (immunodeficiency, autoimmune disease, hematological disease). Search for
      subcutaneous T-cell lymphoma is mandatory, but is a diagnostic challenge. Such
      lymphomas are associated with histologic features of histiocytic cytophagic
      panniculitis. PATHOPHYSIOLOGY: Histiocytes in the histiocytic cytophagic
      panniculitis are activated by an abnormal cytokine secretion (interferon gamma,
      granulocyte/macrophage colony stimulating factor, phagocytosis inducing factor,
      ...) from neoplastic or reactive T cells. CLINICAL TRIALS: Untreated, the course
      of the disease is usually lethal. Etiologic treatment should be provided whenever
      possible. Symptomatic treatment consists in transfusion and corticosteroid
      therapy. Etoposide, and sometimes cyclosporin, have been reported to be
      efficient. Some authors recommend that histiocytic cytophagic panniculitis should
      always be treated with a CHOP-like polychemotherapy. More recently, good results
      were obtained with high dose intravenous immunoglobulin and this treatment
      therefore deserves further evaluation.

PMID- 9537004
TI  - [Xeroderma pigmentosum].
AB  - MAIN CLINICAL FEATURES: Xeroderma pigmentosum is a rare, recessive disorder
      clinically characterized by extreme photosensitivity, pigmented abnormalities of
      the skin-exposed areas, and frequent ocular and neurological abnormalities.
      Xeroderma pigmentosum syndrome is associated with an estimated 2000-fold increase
      in the risk to develop skin cancer (basal cell carcinoma, squamous cell carcinoma
      and melanoma). A HETEROGENEOUS DISEASE: Skin or blood cells from Xeroderma
      pigmentosum patients are hypersensitive to killing by ultraviolet and
      hypermutable after ultraviolet C treatment Cell fusion experiments based on
      complementation of repair synthesis have recognized the presence of seven
      Xeroderma pigmentosum groups which exhibit various defects in the initial steps
      of the DNA nucleotide excision repair pathway. A variant Xeroderma pigmentosum
      form has been found to be normal in nucleotide excision repair but abnormal in a
      poorly to be normal in nucleotide excision repair but abnormal in a poorly
      understood postreplication repair process. PATHOPHYSIOLOGY: The Xeroderma
      pigmentosum complementation groups differ in terms of severity of clinical,
      cellular and genetic features. Molecular and biochemical studies of the Xeroderma
      pigmentosum syndrome have led to a better understanding of the mechanisms of
      ultraviolet-induced sensitivity and the mechanism of cancer development after
      ultraviolet exposure.

PMID- 9537005
TI  - Complications of carbon dioxide laser resurfacing. An evaluation of 500 patients.
AB  - BACKGROUND: Cutaneous laser resurfacing with high-energy, pulsed and scanned
      carbon dioxide (CO2) lasers has become popularized for the treatment of a variety
      of cutaneous indications, but potential complications and side effects remain a
      large concern. Despite the recent boom in cutaneous laser resurfacing procedures,
      there remains a relative paucity of written information documenting laser
      complication rates. OBJECTIVE: The purpose of this study was to identify and
      report the complications that occurred after cutaneous CO2 laser resurfacing
      within a large patient population. METHODS: A retrospective analysis and chart
      review was performed in 500 consecutive patients who underwent cutaneous laser
      resurfacing of 1589 facial regions with the UltraPulse CO2 laser by a single
      operator. Side effects and complications relating to infection, postoperative
      healing, pigmentary changes, and scarring were tabulated. RESULTS: The most
      common complication observed was postoperative erythema, which occurred in all
      patients, lasting an average of 4.5 months. Hyperpigmentation was seen in 37% of
      patients with a higher rate in darker skin phototypes. Acne flares, milia
      formation, and dermatitis occurred in 10-15% of patients. Postoperative infection
      with herpes simplex virus (HSV) was observed in 7.4% regardless of prior HSV
      history. Hypopigmentation, scarring, and other local or disseminated infections
      occurred in < 1% of this study population. CONCLUSIONS: Cutaneous CO2 laser
      resurfacing is a relatively safe procedure with a low complication profile.
      Proper laser treatment protocol and postoperative management is important in
      reducing side effects and complications.

PMID- 9537006
TI  - Salicylic acid peels for the treatment of photoaging.
AB  - Several chemical agents are currently used to perform superficial chemical peels
      of the face. These include trichloracetic acid (15-30%), alpha-hydroxy acids
      (e.g., glycolic acid, 40-70%), and Jessner's solution (14% lactic acid, 14%
      resorcinol, and 14% salicylic acid). We have developed salicylic acid, a beta
      hydroxy acid, at a higher strength (30% in a hydro-ethanolic vehicle) as an
      alternative peel. This peel has distinct advantages for resurfacing moderately
      photodamaged facial skin. We have peeled patients singly and multiply at 4-week
      intervals. The benefits are fading of pigment spots, decreased surface roughness,
      and reduction of fine lines.

PMID- 9537007
TI  - Effect of topical vitamin C on postoperative carbon dioxide laser resurfacing
      erythema.
AB  - BACKGROUND: Postoperative erythema of several months duration is a universal and
      problematic side effect of cutaneous carbon dioxide (CO2) laser resurfacing.
      OBJECTIVE: This study was conducted in order to determine the effectiveness of
      two formulations of topical ascorbic acid in reducing the degree and duration of
      post-CO2 laser resurfacing erythema. RESULTS: The application of topical L
      ascorbic acid in an aqueous formulation resulted in a significant decrease in
      post-CO2 laser resurfacing erythema by the eighth postoperative week when
      compared with laser-irradiated skin that had not received topical vitamin C. The
      application of topical ascorbic acid in a cream formulation did not result in a
      significant reduction in post-CO2 laser resurfacing erythema. CONCLUSION: Topical
      L-ascorbic acid, when used in an appropriate vehicle and when initiated at an
      appropriate postoperative period, may decrease the degree and duration of
      erythema after cutaneous CO2 laser resurfacing. It is presumed that the anti
      inflammatory effect of vitamin C is responsible for the clinical changes observed
      in this study.

PMID- 9537008
TI  - The etiology of prolonged erythema after chemical peel.
AB  - BACKGROUND: As the number and methods of skin resurfacing procedures are
      increasing, there is a small number of patients that develop a prolonged
      inflammation during the postoperative period. OBJECTIVE: We attempted to
      correlate risk factors for the development of prolonged postpeel erythema (PPPE)
      and inflammation. A treatment regimen will be described to eliminate permanent
      skin changes. METHODS: A retrospective chart review is presented to define and
      correlate risk factors for the development of PPPE and a treatment protocol is
      described. The setting is a large multisurgeon aesthetic center. Two-hundred and
      thirty-six consecutive chemical phenol peels on 196 patients over a 2-year period
      were reviewed. RESULTS: Eleven percent of patients developed PPPE. Allergy to
      tape was the only factor significantly correlated with PPPE. All patients had
      complete resolution of skin changes with appropriate treatment. CONCLUSION: A
      small population of patients undergoing skin resurfacing procedures will develop
      prolonged erythema. No major risk factor could be correlated with its
      development. A treatment plan was devised and was successful in all cases.

PMID- 9537009
TI  - The Q-switched neodymium (Nd):YAG laser with quadruple frequency. Clinical
      histological evaluation of facial resurfacing using different wavelengths.
AB  - BACKGROUND: The Q-switched neodymium (Nd):YAG laser with quadruple frequency is
      very effective for the treatment of tattoos, pigmented lesions, and vascular,
      benign lesions. It is also an option for treating rhytides, scars, and facial
      pigmentations. OBJECTIVES: This paper is based on a series of patients with
      periocular and perioral rhytides, postacne scars, and melanic and vascular eyelid
      pigmentation who were treated with the Q-switched Nd:YAG laser with quadruple
      frequency. METHODS: The patients were divided in three separate groups: facial
      wrinkles, postacne scars, and eyelid pigmentation. All were biopsied before and
      after the laser treatment. Different wavelengths (1064, 650, 585, and 532 nm)
      were used in order to study the clinical improvement and the histological changes
      that occurred several weeks following the laser treatment. Additionally, these
      biopsies aided in observing specific histological characteristics related to
      applying the different wavelengths by evaluating them along with the clinical
      results. RESULTS: Very good results were achieved in the 22 facial wrinkle cases
      with two treatments. Excellent results were achieved in the 28 postacne patients,
      and the outcome of the 16 patients with pigmentation of the eyelids were
      considered good. CONCLUSION: The Q-switched Nd:YAG laser with quadruple frequency
      can be classified as a valid alternative for facial resurfacing. The results
      obtained are comparable to those with the pulsed carbon dioxide lasers, plus it
      has the advantage of being effective on vascular lesions.

PMID- 9537010
TI  - Previous diathermic therapy at the site of the development of basal cell
      carcinomas. A hypothesis of association.
AB  - BACKGROUND: Factors associated with the development of basal cell carcinomas
      (BCCs) are radiation exposure, sunlight, trauma, and burns. OBJECTIVE: We wish to
      further document the relationship between the development of BCCs and previous
      diathermic exposure for therapeutical purposes. Moreover, we compared the
      histological subtypes of BCCs developed in patients with or without previous
      therapy. METHODS: A retrospective study of 1053 patients with BCCs seen at our
      dermatologic clinic was performed. RESULTS: Twenty-three patients had histories
      of diathermic therapy for different osteoarticular problems. The interval of time
      between the treatments and the appearance of the tumor was 12-31 years. The
      histologic subtypes involved were the same of other BCCs on the same areas.
      CONCLUSIONS: Our study supports the association of BCCs and diathermic therapy in
      the development of the tumor of the previously treated areas. Histological
      subtypes do not seem to be affected by environmental factors but are a
      characteristic of the site location of the tumor.

PMID- 9537011
TI  - Dermatologists' attitudes toward independent nonphysician electrolysis practice.
AB  - BACKGROUND: Dermatologists' attitudes toward independent electrolysis practice by
      nonphysicians has historically ranged from the critical to the praiseworthy. It
      is hypothesized that dermatologists' attitudes toward independent electrolysis
      practice by nonphysicians is related to physicians' perception of licensing
      requirements for independent nonphysician electrologists (INE). METHODS: Nine
      hundred and thirty-seven fellows of the American Academy of Dermatology (AAD)
      residing in the Southern United States were anonymously surveyed about
      independent electrolysis practice by nonphysicians. The results of the survey
      were analyzed using the Pearson chi-square test. RESULTS: Dermatologists who
      perceived that licensing was required for INE were significantly more likely to
      refer patients to INE for hair removal (P = 0.001) and prescribe EMLA cream
      (lidocaine 2.5% and prilocaine 2.5%) to patients requesting it for electrolysis
      performed by INE (P = 0.001). However, those dermatologists who had electrolysis
      services available in their practice settings (15.1%) were significantly less
      likely to refer patients to INE (P = 0.001) and to prescribe EMLA cream to
      patients seeking electrolysis from INE (P = 0.034). Only 5.7% of responding
      dermatologists supported the use of hair removal lasers by INE. CONCLUSION:
      Dermatologists' attitudes toward INE generally appear to be positively related to
      perceived licensure requirements for INE, but these positive attitudes do not
      extend to independent laser use by nonphysician electrologists for hair removal.

PMID- 9537012
TI  - Repigmentation in vitiligo patients. Melanocyte transfer via ultra-thin grafts.
AB  - BACKGROUND: Several years ago, a successful surgical technique for treating
      depigmentation resulting from burn injuries was developed. OBJECTIVE: The purpose
      of this study was to investigate results of dermabrasion with melanocyte
      transplantation using new modifications of the technique in patients with
      vitiligo. METHODS: We performed 17 procedures on 12 patients with stable
      vitiligo. The epithelium of the vitiliginous areas was removed by dermabrasion.
      The dermabraded area was then reepithelialized with ultra-thin sheet grafts,
      which more recently were meshed and partially expanded. RESULTS: Good to
      excellent repigmentation was observed in 88% of the procedures. Scarring did not
      develop in the repigmented or donor site regions. The final color match has been
      good to excellent. CONCLUSIONS: This technique has proven beneficial in 88% of
      the procedures on our patients. Both our patients and we feel that this provides
      a valuable treatment option in patients who have failed medical management.

PMID- 9537013
TI  - Initial clinical evaluation of the NovaScan carbon dioxide laser handpiece.
AB  - BACKGROUND: This report summarizes an institutional review board-approved 6-month
      study with the NovaPulse carbon dioxide (CO2) laser utilizing the NovaScan
      handpiece in facial skin resurfacing applications. OBJECTIVE: This study
      comprised the initial clinical evaluation (pre-FDA approval) of this device.
      METHODS: A total of 54 patients underwent 56 laser procedures: 36 full face and
      20 regional procedures. RESULTS: Following healing, there was a 91% satisfaction
      rate. The mean laser-on times were: full face, 27 min; perioral, 7 min;
      periorbital, 3 min; glabellar, 2.5 min; scar, 5 min; and epidermal lesions, 6
      min. CONCLUSIONS: The NovaScan CO2 laser handpiece is a safe tool for skin
      resurfacing. In its initial use over a 6-month period there were no device
      related complications.

PMID- 9537015
TI  - Benign symmetric lipomatosis Launois-Bensaude successfully treated with extensive
      plastic surgery.
AB  - Benign symmetric lipomatosis is a rare condition predominantly seen in male
      patients. The etiology is unknown, and therapy is difficult, although liposuction
      has had effect. We describe a 38-year-old male patient who had suffered from
      severe adipositas since the age of 7. Due to an ulceration in the groin, he later
      needed intensive care, and in order to normalize his condition, extensive
      surgical treatment became necessary.

PMID- 9537014
TI  - Miniflap hair restoration.
AB  - BACKGROUND: Flap reconstruction of the scalp has traditionally required multiple,
      delayed procedures, an extensive principle operation, and several minor revision
      surgeries to produce the optimal end result. The entire protocol had to be
      repeated for each subsequent flap. Flap reconstructions only covered a moderate
      portion of the bald scalp of the later-staged patient. This hair restoration
      process required considerable surgical skill on the part of the operator and
      tenacity on the part of the patient. OBJECTIVE: A system of short, nondelayed
      flaps was developed to shorten this comparatively long, multi-staged process and
      reduce the risk of flap compromise. METHODS: Initially, the patient underwent a
      two-step, scalp-lifting procedure to reduce the width of bald scalp to be
      spanned. At later sessions, anteriorly based flaps were outlined from the margin
      of the lifted scalp and rotated into the desired configuration. RESULTS: In 29
      flaps rotated to date in 13 patients, flap viability was excellent and interflap
      scarring acceptable. Hair direction was readily adapted to the patients' desires.
      Case examples are presented. CONCLUSION: Staged scalp-lifting with miniflap
      reconstruction of the scalp is a preferred option for hair relocation in selected
      cases.

PMID- 9537016
TI  - Periductal mastitis. Masquerading as carcinoma.
AB  - Periductal mastitis (mammary duct ectasia) is a little appreciated, often
      unrecognized entity that may present to the dermatologist. We present our
      experience with this disease and hope to familiarize the reader with a condition
      not well known to most dermatologists. Periductal mastitis is a benign mammary
      duct disease that begins with periductal inflammation and progresses to ductal
      dilatation with minimal inflammation (ductal ectasia). The clinical and
      radiographic appearance of this disease can be indistinguishable from carcinoma
      of the breast.

PMID- 9537017
TI  - Nodular hidradenoma. A report of three cases and review of the literature.
AB  - BACKGROUND: Nodular hidradenoma is a rare adnexal tumor most likely arising from
      the eccrine gland. OBJECTIVE: We describe three cases of a nodular hidradenoma
      presenting as an expanding nodule on the forehead (case 1), left lower extremity
      (case 2), and left neck (case 3). We discuss the clinical and histologic features
      of this tumor and present a review of the literature. CONCLUSIONS: This report
      highlights the salient histologic findings that distinguish nodular hidradenomas
      from other adnexal tumors and emphasizes the benefit of complete local excision
      to prevent recurrence of these tumors.

PMID- 9537018
TI  - Hibernoma. Case report and literature review.
AB  - BACKGROUND: Hibernoma is a rare type of benign tumor that originates in brown
      fat. It has been rarely described in dermatologic literature. OBJECTIVE: To
      report and discuss the clinical and histologic features of a patient with
      hibernoma and review the relevant literature. PATIENT: A large palpable hibernoma
      located in the interscapular area of a 41-year-old female was identified by
      physical examination. The tumor was a brown soft mass measuring 7.0 x 6.0 x 3.0
      cm that involved subcutaneous tissue and was embedded in the trapzius muscle. It
      was a well encapsulated and highly vascular tumor. Histologic examination
      revealed characteristic multivacuolated oval and polygonal cells with
      eosinophilic, granular cytoplasm. CONCLUSION: A hibernoma can be diagnosed on the
      basis of gross physical characteristics and microscopic findings. This is a
      benign tumor with no malignant potential. Excisional biopsy is indicated to
      differentiate hibernoma from well-differentiated liposarcoma. Complete excision
      is the treatment of choice.

PMID- 9537019
TI  - Use of ultra-high frequency electrosurgery (radiosurgery) for cosmetic surgical
      procedures.
AB  - BACKGROUND: Electrosurgery has been used for many decades in medicine. Some
      machines generate ultra-high frequency current waveforms (radiosurgery), which
      minimize collateral tissue damage. OBJECTIVE: Personal experience using
      radiosurgery in the performance of cosmetic surgery is related in the narrative
      form to offer the reader a "how we do it" perspective. CONCLUSION: Radiosurgery
      facilitates the performance of blepharoplasty, face lifting, hair restoration
      surgery, abdominoplasty, nasal reduction sculpturing of rhinophyma, and minor
      cosmetic procedures. Collateral heat damage is minimal allowing rapid healing and
      aesthetically pleasing scars.

PMID- 9537020
TI  - Retinal detachment associated with use of epinephrine in local anesthetic for
      facial surgery.

PMID- 9537021
TI  - Does simultaneous contact cooling reduce intravascular temperature during laser
      irradiation and impinge on selective vascular destruction?

PMID- 9537022
TI  - Re: "At least a nurse anesthetist" may not be enough!

PMID- 9537024
TI  - Characteristics of suppressor cell activity appearing in cocultures of two
      individuals with immunodeficiency with thymoma.
AB  - Suppressor cell activity in two individuals (S1 and S2) with immunodeficiency
      with thymoma (ID-THY) was studied in peripheral blood mononuclear cells in
      pokeweed mitogen-stimulated single culture and cocultures. Secreted Ig was
      measured by radioincorporation and immunoprecipitation after 5-7 days. Control
      cocultures of normal/normal cells showed, in most cases, a percentage observed to
      expected ratio (% O/E) of cpm Ig near 100%. However, augmentation (% of O/E >
      150) was often encountered, whereas suppression (% O/E < 50) was found only once
      in forty-two cocultures. In ID-THY/normal cell cocultures the degree of
      suppression by ID-THY cells varied widely when the same or different cocultivants
      were retested. This finding could be explained in part by an inverse correlation
      between the amount of secreted Ig produced by normal cells in single culture and
      the degree of suppression of the same normal by ID-THY cells in cocultures. A
      panel of normal cells were all suppressed when a range of S1 or S2/normal cell
      ratios were tested, weighing against genetic differences in suppressibility in
      the above system. ID-THY cells failed to block Ig secretion of human
      lymphoblastoid line cells, suggesting that the mechanism of suppression was
      related to a block in differentiation rather than interference with Ig synthesis
      per se. An experiment using cocultivants separated by a Millipore membrane showed
      that suppression was mediated by a humoral factor.

PMID- 9537023
TI  - Mitogenic activation of human lymphocytes: a protein A plaque assay evaluation of
      polyclonal B-cell activators.
AB  - Using the protein A plaque assay, the capacity of various polyclonal B cell
      activators to induce differentiation in human B lymphocytes was investigated.
      Dextran sulphate and native dextran were both virtually devoid of mitogenic
      properties. Lipopolysaccharide, however, was found to be a potent mitogen in
      human cells that, although giving rise to low DNA synthetic response, induced
      high numbers of immunoglobulin-synthesizing cells. Mean plaque-forming cell (PFC)
      numbers in healthy blood donors assayed on the optimal day (days 5-7) were 23,493
      IgM/10(6) cells, 11,288 IgG/10(6) cells, and 2643 IgA/10(6) cells. Values
      obtained in spleen cells, peaking at days 4-6, were slightly higher. Purified
      protein derivative (PPD) was equally or even more effective than
      lipopolysaccharide (LPS) in generating PFC of different subclasses in peripheral
      blood with mean of 29,241 IgM/10(6), 21,269 IgG/10(6), and 3681 IgA/10(6). PPD
      furthermore induced a marked DNA synthetic response in human lymphocytes. These
      data suggest that LPS and PPD may both be used as functional markers in human
      cells when analysing patients with a suspected immunodeficiency state. It is
      suggested that cultures should be assayed using the protein A plaque assay,
      thereby being able not only to investigate the individual immunoglobulin classes
      but also to avoid the possible hazards involved in measuring antigen-specific
      responses in patients whose prior immunization to the antigen tested can never be
      totally excluded.

PMID- 9537025
TI  - D-penicillamine in vivo enhances lymphocyte DNA synthesis: role of macrophages.
AB  - Administration of D-penicillamine (50 mg/kg/day orally) for 4 days increased the
      uptake of 3H-thymidine (3H-TdR) in unstimulated and concanavalin-A-stimulated
      unseparated lymph node and spleen cells from Lewis rats. Increased 3H-TdR
      incorporation was also found in cultures depleted of adherent cells. D
      Penicillamine treatment did not increase the incorporation of 3H-TdR in lymph
      node and spleen cells from rats concomitantly treated with the selective
      macrophage toxin silica. In contrast, treatment with D-penicillamine during the
      last 4 days of silica treatment sometimes resulted in a marked decrease in 3H-TdR
      incorporation. It is suggested that D-penicillamine treatment in vivo is able to
      enhance the responsiveness of the lymphocytes, dependent on the presence of
      functionally intact macrophages. The increased response vanished after 2-3 weeks,
      even with continuous administration of D-penicillamine.

PMID- 9537026
TI  - Immunization with the light chain and the VL domain of the isologous myeloma
      protein 315 inhibits growth of mouse plasmacytoma MOPC315.
AB  - Prior immunization of BALB/c mice with free light chains from myeloma protein 315
      (L315) and its variable domain (VL315) inhibited the growth of subcutaneously
      injected MOPC315 tumour cells. The growth suppression observed after immunization
      with L315 was equivalent to that which resulted from immunization with the
      complete M315. VL315 and non-polymerized L315 did not elicit specific antibodies.
      Polymerized L315 induced both suppression of MOPC315 growth and antibodies
      specific for free L315; however, these antibodies did not react with the complete
      M315, nor were they absorbed by MOPC315 tumour cells. The data indicate that the
      suppression of tumour growth was mediated by specifically sensitized cells acting
      in the absence of antibodies against M315 or L315. Immunization with the variable
      domain of the heavy chain from M315 (VH315) had no effect on the growth of
      MOPC315. The M315 fragments and subunits that induced growth suppression were
      thus identical with those capable of inducing T helper cells in BALB/c mice.

PMID- 9537027
TI  - Binding of murine myeloma proteins of different Ig classes and subclasses to Fc
      reactive surface structures in gram-positive cocci.
AB  - Twelve different murine myeloma proteins were tested for binding to seventy Gram
      positive strains belonging to group A, C and G streptococci and to Staphylococcus
      aureus. Group A streptococci, known to bind human IgG, were incapable of binding
      any of eight murine IgG immunoglobulins tested except for one strain that bound
      an IgG2b myeloma protein. In contrast, group C and G streptococci interacted with
      murine immunoglobulins of subclasses IgG2a, IgG2b and IgG3, and G strains also to
      a lesser extent with IgG1. Bovine and equine-group C streptococci did not differ
      from human group C streptococci in their IgG reactivity. Staphylococcal strains
      showed a high reactivity with murine myeloma components of IgG subclasses 2a, 2b
      and 3 and a low but definite binding of an IgG1 myeloma protein. IgA myeloma
      protein S-122 interacted with nine of fifteen group A streptococci. This binding
      could not be inhibited by human IgG and the reactivity is thus different from Fc
      mediated binding of immunoglobulins. One of three IgA myeloma proteins tested,
      TEPC 15, bound to staphylococci. The Fc specificity of this interaction was
      confirmed by chromatography on protein A-Sepharose and by inhibition studies
      using polyclonal human IgG. The protein A reactivity of this monoclonal protein
      was detected in IgA aggregates and absent in the monomeric form of IgA.

PMID- 9537028
TI  - Conditions for induction of specific and polyclonal antibody production by Cowan
      1 bacteria and by pokeweed mitogen.
AB  - Cowan 1 bacteria and pokeweed mitogen (PWM) were used to induce the formation of
      direct plaque-forming cells (PFC) against sheep erythrocytes (SRBC) by human
      peripheral blood lymphocytes in vitro. It was necessary to absorb the serum
      supplement with SRBC before culture to obtain anti-SRBC PFC. Alternatively, sheep
      serum could be added to the cultures. The PFC response was specific, and the
      response was equally high in cultures with a mixture of absorbed and non-absorbed
      serum as in cultures with absorbed serum only. Cowan 1 and PWM could also induce
      synthesis and secretion of both IgM and IgG polyclonal antibodies. Absorption
      with SRBC or addition of sheep serum had no effect on this synthesis. Thus it
      seems likely that the induction of anti-SRBC PFC by Cowan 1 or PWM needs the
      presence of SRBC antigen and is the result of a synergism between mitogen and
      antigen. Consequently, the anti-SRBC PFC response obtained after stimulation with
      Cowan 1 or PWM in SRBC-absorbed serum does not reflect a true polyclonal antibody
      response.

PMID- 9537029
TI  - A primary immune response to dextran B512 is followed by a period of antigen
      specific immunosuppression caused by autoanti-idiotypic antibodies.
AB  - After a primary immune response to the alpha 1-6 epitope of dextran B512, dextran
      high responder strains exhibit a specific inability to produce IgM and IgG
      antibodies against this epitope, although they gave an expected secondary
      response to horse erythrocytes. Spleen cells from dextran-primed and-suppressed
      mice responded well to dextran after transfer to lethally irradiated previously
      untreated mice, indicating that tolerance or exhaustive proliferation of dextran
      reactive B cells is not responsible. Thymus-dependent dextran-protein conjugates
      also induced specific suppression. Suppression to both dextran and horse
      erythrocytes could be passively transferred into untreated recipients with immune
      serum. However, after absorption with horse erythrocytes and dextran, passive
      serum transfer only suppressed the response to dextran. It is suggested that the
      specific immunosuppression was caused by the appearance of autoanti-idiotypic
      antibodies directed against the immunoglobulin receptors of dextran-reactive B
      cells.

PMID- 9537030
TI  - Properties of purified papain-solubilized rat AgB antigens and reactivity of a
      xenoantiserum against the isolated antigens.
AB  - Rat AgB transplantation antigens were isolated after papain digestion of spleens
      from the inbred strain Hooded Lister. Both subunits of the AgB antigens were
      present in the purified material. Some physical characteristics of the antigens
      have been determined. An antiserum, raised in a rabbit, against the purified
      material reacted exclusively with AgB antigens on splenocytes but detected novel
      structures on both adult and embryonic fibroblasts. These structures,
      antigenically related to AgB antigens, were not detected on plasmacytoma or
      hepatoma cells, nor did they display any antigenic similarity with rat beta 2
      microglobulin. Radioimmunoassays specific for the AgB antigen heavy chain and for
      beta 2-microglobulin, respectively, were used to estimate the contents of these
      antigens in several tissues. Spleen and thymus exhibit the largest density, while
      brain is almost devoid of these antigens.

PMID- 9537031
TI  - Human lymphoblastoid cell line producing specific antibody against Rh-antigen D.
AB  - A lymphoblastoid cell line producing specific anti-Rh antibody against D
      determinant was established by Epstein-Barr virus (EBV) infection. The
      lymphocytes were from an immunized male donor with high titre of anti-D antibody.
      The cells were preselected by rosetting them with Rh-positive erythrocytes before
      EBV infection. The cell line produced specific antibody of IgG class, namely IgG1
      subclass, but it also produced nonspecific IgM and IgG. By rerosetting the cell
      line, the specific antibody-producing population could be enriched and the
      antibody titre increased in the culture supernatant to the level of immune sera.

PMID- 9537032
TI  - Detection of muramidase (lysozyme)-secreting leucocytes at the single-cell level
      by a protein A plaque assay.
AB  - Using a modification of the protein A plaque assay, muramidase (lysozyme)
      producing leucocytes were detected as plaque-forming cells. In the presence of
      anti-muramidase Ig and complement the secreted lysozyme resulted in lysis of
      protein-A-coated target erythrocytes. By the use of a monolayer technique
      individual plaque-forming cells could be identified by staining procedures.
      Granulocytes as well as monocytes were found to produce muramidase and thus to
      form plaques. This method could serve as a useful tool when studying lysozyme
      secretion. Furthermore, by the use of appropriate antisera, this method could be
      employed for the study of any cell type (any secretion), provided enough
      molecules are being secreted.

PMID- 9537033
TI  - Antibody-coated sheep erythrocytes suppress the ability of polyclonal B-cell
      activators to induce plaque-forming cells against sheep erythrocytes.
AB  - The primary immune response to untreated sheep erythrocytes (SRBC) in vitro was
      suppressed by the addition of antibody-coated SRBC. A mixture of SRBC and
      antibody-coated SRBC also suppressed the induction of anti-SRBC plaque-forming
      cells by the polyclonal B cell activators lipopolysaccharide, purified protein
      derivative of tuberculin, and native dextran. Injection of a mixture of SRBC and
      antibody-coated SRBC into mice led to an increased response to SRBC. It seems
      plausible from the in vitro findings that the Fc part of antibodies complexed to
      an antigen can exert a negative signal on antigen-specific B cells that cannot be
      overcome by positive signals delivered by polyclonal B cell activators.

PMID- 9537035
TI  - Genetic specificity of primary and secondary proliferative and cytotoxic
      responses of human lymphocytes grown in continued culture.
AB  - Human T peripheral blood lymphocytes were grown in continued culture using
      conditioned medium obtained from phytohaemagglutinin-stimulated, pooled human
      leucocytes. These cultured T cells (CTC) were tested in mixed lymphocyte culture
      (MLC) and cell-mediated lympholysis (CML) assays to determine the genetic
      specificity of their proliferative and cytotoxic responses. Primary responses
      were measured after initial in vitro stimulation by allogeneic cells, and
      secondary responses were measured after a second in vitro stimulation by
      allogeneic cells. Both primary and secondary proliferative responses were found
      to be stimulated by alloantigens controlled by the HLA region and, more
      specifically, by antigens of the HLA-D region, in accordance with the responses
      of normal peripheral blood T lymphocytes. When CTC were established from
      unsensitized PBL and then stimulated with allogeneic cells, they could respond by
      proliferation in MLC, but, in contrast to PBL, they did not show subsequent
      cytotoxic responses. On the other hand, CTC established from PBL that had been
      stimulated first with allogeneic cells in either primary or secondary MLC
      displayed high levels of cytotoxic reactivity in CML. The strongest cytotoxicity
      was directed against allospecificities controlled by the HLA region and specific
      for the MLC-stimulating cells, but lower levels of cross-reactive cytotoxicity
      were also observed.

PMID- 9537034
TI  - Synthesis of secretory component by rat hepatocytes in culture.
AB  - Normal rat hepatocytes were isolated and cultivated in vitro. Synthesis of
      secretory component was demonstrated by its accumulation in the culture medium,
      as measured by radioimmunoassay; by incorporation of 14C-leucine in the protein
      specifically precipitated with anti-secretory component antiserum; and by a
      positive precipitin reaction of concentrated culture medium with the same
      antiserum. The results explain the high levels of secretory component found in
      rat bile and render plausible a mechanism of hepatic IgA transfer involving
      secretory component as the hepatocyte membrane receptor for polymeric IgA.

PMID- 9537036
TI  - Cell interactions that regulate the T-cell dose-response profile to concanavalin
      A.
AB  - We have tested the ability of structures on macrophage (M phi) membranes (M phi
      MEM) and on several other types of cells with Fc receptors to affect the DNA
      synthetic response of concanavalin-A-stimulated T cells. Of the cells tested,
      only M phi-MEM have the capacity to relieve the suppression produced by supra
      optimal doses of the mitogen. The M phi-MEM do not increase Con A responses by
      altering the stimulatory capacity of the Con A. These observations, analysed
      together with previous results, which have indicated that live intact M phi are
      required for the transfer of information between lymphocyte sets and that M phi
      MEM preparations can act as competitive antagonists for this function, are
      interpreted as follows: some supraoptimal doses of Con A activate suppressor
      cells, which are responsible for limiting the DNA synthetic response to the
      mitogen; the M phi-MEM abrogate this suppression by absorbing the signal that
      activates the suppressor cell. Kinetic studies suggest that the M phi-MEM do not
      affect the activity of already activated suppressor cells. We also found that Con
      A usually activates two separately responding T-cell populations with different
      sensitivities to dose and to time of contact with mitogen and that the
      suppression of both populations can be relieved by M phi-MEM. These results
      support the notion that the overall immunological circuit is composed of multiple
      independently regulated mini-circuits, with M phi acting as transmission posts
      for intra- and perhaps also inter-circuit communication.

PMID- 9537037
TI  - Activation of human T and B cells by rabbit anti-human beta 2-microglobulin.
AB  - Rabbit anti-human beta 2-microglobulin (anti-beta 2m) increased the highest DNA
      synthesis in unseparated lymphocytes or artificially composed mixtures enriched
      in T and B cells. In enriched T and B cells no or low stimulation was seen. The
      maximal response by IgG anti-beta 2m was seen in proportions of enriched T/B
      cells, being 3:1 for blood lymphocytes and 1:1 for spleen cells, which are the
      same as the physiological proportions of T and B cells in these lymphoid organs.
      Whereas unseparated lymphocytes gave a peak response on day 3, enriched B cells
      had a peak response on day 6. Fab anti-beta 2m did not activate enriched T cells
      but increased DNA synthesis in enriched B cells to about the same extent as
      unseparated lymphocytes and mixtures of enriched T and B cells. The proportion of
      sheep erythrocyte rosette-forming cells (E-RFC) decreased after stimulation by
      anti-beta 2m and increased after stimulation by phytohaemagglutinin. However, as
      revealed by autoradiography, a proportion of lymphocytes activated by anti-beta
      2m were E-RFC and this proportion increased with increasing stimulation by anti
      beta 2m. DNA synthesis induced by anti-beta 2m was unchanged for spleen cells and
      slightly decreased for blood lymphocytes when phagocytic cells were removed by
      iron treatment. Supernatants from lymphocytes activated by anti-beta 2m only
      induced low DNA synthesis in enriched T or B cells. Experiments with mitomycin
      treated cells indicate that cooperation and close contact between T and B cells
      are needed for activation by IgG anti-beta 2m. T cells are needed for B cell
      activation by anti-beta 2m and B cells are required for T cell activation to
      occur.

PMID- 9537038
TI  - Long-term maintenance of HLA-D restricted T cells specific for soluble antigens.
AB  - Lymphocytes from donors sensitized to soluble protein antigens tuberculin (PPD)
      and tetanus toxoid were stimulated in vitro with these antigens. The blasts were
      isolated on density gradients and maintained in long-term proliferating culture
      by the addition of supernatants from phytohaemagglutinin-stimulated (PHA)
      cultures. Blasts can be shown to retain specificity for the original stimulating
      antigen as measured by stimulation of DNA synthesis, but only when the antigen is
      presented in the company of a cooperating cell population. Autologous irradiated
      peripheral blood lymphocytes provide the best cooperation, but donors who share
      HLA-D antigens will also allow for continued proliferation in the presence of the
      appropriate soluble antigen. Donors sharing at HLA-A, -B, or -C show minimal
      ability to cooperate. The soluble antigen-specific blast cells do not manifest
      alloreactivity. The data are discussed with regard to possible application to
      clinical histocompatibility typing and to the implications of selfrecognition in
      the immune response.

PMID- 9537040
TI  - A new quantitative fluorimetric assay for phagocytosis of bacteria.
AB  - We describe a new quantitative fluorimetric assay for phagocytosis of bacteria. A
      suspension of fluorescein-labelled bacteria (Micrococcus lysodeikticus) is mixed
      and incubated with phagocytes. After fixation with paraformaldehyde, the excess
      non-phagocytosed and adsorbed bacteria are lysed with a solution of lysozyme in
      phosphate-buffered saline. After washing of the phagocytes, the fluorescence of
      those that have ingested the labelled bacteria is measured with a
      spectrofluorimeter. We report results obtained with different types of phagocytes
      which show that this method allows sensitivity, saturation and kinetic studies
      and the calculation of a phagocytic index.

PMID- 9537039
TI  - Antibody secretion and DNA synthesis induced by lipopolysaccharide in enriched
      human lymphocyte subpopulations.
AB  - Lipopolysaccharide (LPS)-induced human lymphocyte activation was analysed with
      regard to DNA synthesis and antibody secretion. Antibody secretion was measured
      as plaque-forming cells (PFC) against fluorescein isothiocyanate (FITC)-coupled
      sheep erythrocytes (SRBC) or protein-A-coupled SRBC in the presence of developing
      antiserum against human IgG, IgA and IgM subclasses. By co-culturing lymphocytes
      with various concentrations of mitomycin, without impairing cell viability,
      inhibition of DNA synthesis and antibody secretion by LPS was correlated.
      Antibody secretion against FITC-SRBC or protein A-SRBC was not stimulated by LPS
      in B cells enriched by elimination of SRBC rosette-forming cells (E-RFC). In
      mixtures of enriched T and B cells the number of PFC was much lower than in
      unseparated lymphocytes, but the highest number of PFC was seen in the enriched E
      RFC. However, DNA synthesis by LPS was induced in enriched B cells and not in
      enriched T cells. The highest DNA synthesis was seen for unseparated lymphocytes.
      Furthermore, autoradiography studies and experiments in which activated
      lymphocytes were separated revealed that LPS predominantly stimulated DNA
      synthesis in non-E-RFC, presumably B cells and only activated a small proportion
      of E-RFC. Finally, antibody secretion induced by LPS was unchanged following iron
      treatment but was inhibited by cells adherent to plastic.

PMID- 9537041
TI  - Epstein-Barr virus-induced lymphoblastoid cell lines from patients with primary
      immunodeficiency diseases.
AB  - Peripheral lymphocytes from eight patients with congenital immunodeficiency
      diseases were infected with Epstein-Barr virus (EBV) in an attempt to establish B
      lymphoblastoid cell lines (LCL). These patients included three boys with
      congenital agammaglobulinaemia, two girls with hypogammaglobulinaemia, one boy
      with common variable immunodeficiency, one boy with severe combined
      immunodeficiency with adenosine deaminase deficiency, and one boy with DiGeorge
      syndrome. Five of the patients bore no surface immunoglobulins (sIg) on their
      peripheral lymphocytes. LCL were established from seven of the eight patients.
      All the LCL established formed rosettes with EAC3 and had the ability to produce
      cytoplasmic immunoglobulins (cIg) of various classes. Culture supernatants
      concentrated up to 100-fold developed precipitin bands by Ouchterlony's method
      with antisera to human Ig in all the established LCL. These results suggested
      that both sIg-, cIg- and C3+ cells and sIg+, cIg- and C3+ cells might be the
      target cells for EBV and that sIg-, cIg- and C3+ cells might be the precursor
      cells of B lymphocytes.

PMID- 9537042
TI  - Mouse/human T-cell hybrids rosetting with sheep erythrocytes.
AB  - Hybrid cells have been recovered from selective culture medium after fusion of
      concanavalin-A-activated human lymphocytes with an AKR mouse thymoma (BW 5147).
      After 6 months of culture twenty-seven out of forty-nine clones still contained
      human chromosomes. Human chromosome 6 was present in 89% of these clones, and
      human X in 70%. Clones from one hybrid line contained several human chromosomes.
      In twelve of the clones carrying human chromosomes, the rosetting with sheep
      erythrocytes (SRBC) was 3 times as high as in the BW 5147 cell line. All these
      clones carried the human chromosome 6, and eight clones contained the human X
      chromosome as well. In some of these clones (25%) chromosome 6 was the only human
      one present. In the two clones in which human chromosome 6 was completely
      missing, the rosetting with SRBC was at the level of the BW line. We therefore
      suggest that genes on human chromosome 6 are responsible for rosetting with SRBC.

PMID- 9537043
TI  - Specific and nonspecific immunoregulatory events in the clonal response of human
      lymphocytes in vitro.
AB  - Stimulation of sensitive leucocyte populations with near optimal concentrations
      of soluble microbial antigens results in vigorous lymphocyte proliferation when
      3H-thymidine incorporation is measured after 4-8 days. Lymphoblasts in these
      cultures revert to small lymphocytes after 10-14 days, at which time they are
      often refractory to any stimulant including the original incubating antigen. When
      these primed lymphocytes are irradiated with 500-1000 R to block their
      proliferation and added to fresh leucocyte culture from the same individual
      (autologous), they usually, but not invariably, reduce the proliferation of the
      unirradiated fresh leucocyte cultures. Exposure to 6000 R reduced the suppressor
      activity. Reduction was specific for the microbial antigen with which they were
      originally generated, but, more often, a combination of both specific and
      nonspecific suppression was observed. These data provide good evidence, with
      reciprocal specificity, for the generation of antigen specific suppression in
      vitro.

PMID- 9537044
TI  - Proliferation of C3H x CBA hybrid lymphocytes in the spleens of irradiated CBA
      mice: linkage to the Mls-gene.
AB  - Lymphocytes from C3H x CBA F1 mice, lacking detectable Mls-antigens, can
      specifically inactivate T-cell clones from the H-2-identical strain CBA, which
      are reactive against the C3H-determined Mls-antigen. Such F1 lymphocytes also
      proliferate in the spleens of irradiated CBA mice. The age dependence of the
      mixed lymphocyte culture stimulatory capacity and the capacity to proliferate in
      irradiated CBA recipients of lymphocytes from C3H x CBA F1 mice were compared. It
      was observed that appearance of Mls-bearing cells is preceded by the appearance
      of F1 cells with strong proliferative capacity in irradiated CBA recipients. The
      in vivo proliferative response is also dependent on the age of the recipient. The
      varying response is not reflected in the quantity of anti-C3H Mls-reactive cells
      in CBA mice. A strong linkage between the genes controlling the above
      proliferative and stimulatory capacities of C3H x CBA lymphocytes was found.

PMID- 9537045
TI  - Proliferation of C3H x CBA hybrid lymphocytes in the spleens of irradiated CBA
      mice: inhibition of this phenomenon by pretreatment of the hosts with C3H x CBA
      spleen cells.
AB  - Lymphocytes from C3H x CBA hybrid mice proliferate intensely in the spleens of
      irradiated CBA mice. Pretreatment of the CBA hosts with C3H x CBA spleen cells,
      known to specifically reduce the T-cell reactivity of the hosts against the
      strongly stimulatory Mls-antigen determined by the C3H-genome, abolished the
      capacity of the host to promote proliferation of C3H x CBA lymphocytes. In
      contrast, proliferation of C3H x CBA bone marrow cells, as measured by splenic
      59Fe incorporation, was unaffected by such pretreatment. By examining the
      capacity of spleen cell populations of (C3H x CBA) x CBA back-cross mice to
      inhibit lymphocyte proliferation, as described above, and to express the C3H
      determined Mls-antigen, it was concluded that these two traits are associated.

PMID- 9537046
TI  - Alteration of T-lymphocyte subpopulations in patients with primary renal diseases
      and systemic lupus erythematosus.
AB  - Forty-eight patients with a variety of primary renal diseases and systemic lupus
      erythematosus (SLE) were examined for the proportion of circulating T lymphocytes
      bearing receptors for IgM (T mu cells) or IgG (T gamma cells). Although the
      control group showed strikingly similar mean values for both T mu and T gamma
      cells, the whole group of patients with primary renal diseases and SLE showed a
      wide scatter of values. Sixteen patients with primary renal diseases and SLE had
      higher proportions of T gamma cells than the control group, whereas seven
      patients with chronic glomerulonephritis (CGN), membranoproliferative
      glomerulonephritis (MPGN), lipoid nephrosis (LN), and SLE showed very marked
      decrease in the proportions of T gamma cells in the peripheral blood. On the
      other hand, six out of the total group of patients had low proportions of T mu
      cells in the peripheral blood. However, no consistent relationship between the
      proportion of T mu and T gamma cells was found in our study. These findings
      indicate that there exists a heterogeneity of T-lymphocyte subpopulation
      distribution in some patients with primary renal diseases and SLE. The possible
      significance of these phenomena in the pathophysiology of renal diseases is
      discussed.

PMID- 9537047
TI  - Expression of human placental cell surface antigens on peripheral blood
      lymphocytes and lymphoblastoid cell lines.
AB  - The expression of human placental cell surface antigens was examined in cells of
      lymphoid origin, including peripheral blood lymphocytes and cultured
      lymphoblastoid cells of bone marrow or thymus derivation. A select group of this
      defined set of surface antigens was detected on all three cell preparations. The
      most remarkable observation was the conspicuous absence of three subunits
      previously demonstrated to be present on all human cell surfaces examined to
      date. Antiserum directed against several placental components prevents adhesion
      and spreading of cells which grow attached to surfaces. These results suggest a
      role for these three glycoproteins in mediating cellular adhesion.

PMID- 9537048
TI  - Spontaneous cell-mediated cytotoxicity (SCMC) in various mammalian species and
      chickens: selective reaction pattern and different mechanisms.
AB  - Cultured cell lines derived from donors of various species served as 75Se- or
      51Cr-labelled targets in microcytotoxicity assays. As in human donors,
      considerable spontaneous cell-mediated cytotoxicity (SCMC) was exhibited by
      peripheral blood lymphoid effector cells from healthy chickens, mink, swine,
      cattle, horses and tigers. Although all target lines tested could be lysed in
      SCMC, there was no 'general SCMC target' for all species or all individuals of
      one species. The selectivity, the kinetics, and the strength of SCMC reflected
      the capacity of the effector cells rather than a 'susceptibility' of the target
      to lysis. Classical major histocompatibility complex products, determinants
      specific for distinct cell types or subpopulations, or antigens associated with
      Epstein-Barr virus, herpes virus ateles, herpes virus papio, or Marek's disease
      virus were not appreciably involved in SCMC. No 'malignant phenotype' on targets
      was required for the cytotoxic effect. Yet undefined xenogeneic, allogeneic, and
      individual structures seem to be involved in SCMC. Depending on their expression,
      a target can be classified as 'species-related' or as 'individual-related'.
      Intermediate forms are conceivable. SCMC might comprise different cytotoxic
      mechanisms. Antibodies are not required for lysis to occur, but serum factors
      including immunoglobulins can have considerable influence on SCMC.

PMID- 9537049
TI  - Cytochemistry of human T-cell subpopulations.
AB  - Acid phosphatase and esterase cytochemistry performed on purified normal human T
      cell populations showed that both methods produced distinctive localized dot
      patterns of reactivity in 60-70% of cells. By examination of rosette preparations
      formed with ox erythrocytes coated with IgM (EAM), with IgG (EAG), or anti-human
      kappa and lambda light chains, it was shown that this pattern of reactivity was
      largely restricted to small T lymphocytes possessing receptors for the Fc of IgM
      (T mu cells). In addition, both B lymphocytes and T cells with receptors for the
      Fc of IgG (T gamma cells) were larger lymphocytes with more abundant cytoplasm
      and usually displayed scattered granular acid phosphatase activity; in esterase
      preparations both cell types were either negative or possessed similar scattered
      granular positivity. As compared with T mu cells, T gamma cells were seen to form
      loose spontaneous rosettes with sheep erythrocytes. Combined esterase and acid
      phosphatase staining showed that both enzyme activities in the T mu cells are
      localized in the same area, and ultrastructural acid phosphatase cytochemistry
      established that this was in distinctive lysosomal structures. T mu staining by
      both esterase and acid phosphatase cytochemistry was greatly reduced after
      rosetting with EAG, but not after rosette formation with EAM or sheep
      erythrocytes.

PMID- 9537050
TI  - T-lymphocyte recognition of the I-EC gene products (Ia) requires concomitant
      recognition of I-AB gene products.
AB  - The murine primed lymphocyte typing (mPLT) assay, based on the sequential
      reactivation of specific immunocompetent, alloantigen-reactive T blast cells in
      secondary mixed leucocyte culture (MLC), has been utilized to define the class II
      I-EC-subregion-associated lymphocyte-stimulating (LS) determinants of the major
      histocompatibility complex (MHC). The test panel of secondary stimulating cells
      has been expanded in this study to include the B10.W lines (mouse strains
      carrying MHC regions derived from wild mice). Data obtained using mPLT cells
      generated in primary MLC between I-EC-subregion-disparate strain combinations
      reveal that (1) an absolute correlation between expression of the serologically
      defined Ia specificities and the capacity to induce subsequent secondary MLC
      activation does not exist, and (2) whereas the serologically defined Ia
      specificities appear to cluster on the alpha-chain of the Ia molecule, T
      lymphocytes recognize either the beta-chain per se or an interaction product of
      the alpha-chain plus beta-chains. Based on these observations, we conclude that T
      and B lymphocytes recognize different antigenic moieties expressed on the MHC
      class II antigens. How these data explain and/or affect several genetic concepts
      is discussed.

PMID- 9537052
TI  - Immunopathologic role of proteoglycan antigens in rheumatoid joint disease.
AB  - Cell-mediated immunity to proteoglycan antigens was assessed by leucocyte
      migration inhibition and by lymphocyte stimulation tests in patients with
      rheumatoid arthritis or with ankylosing spondylarthritis, in patients with
      relapsing synovitis after a single trauma to their knee joints, and in healthy
      donors. Both tests revealed a sensitization in most of the patients examined with
      various proteoglycan antigens derived from human cartilaginous tissues,
      rheumatoid synovial fluid, and species-common antigen of bovine nasal cartilage.
      Antibodies against proteoglycan antigens of human articular cartilage were
      detected by solid-phase radioimmunoassay in eleven out of twenty-nine sera from
      patients with rheumatoid arthritis and in four out of six rheumatoid synovial
      fluids. The results suggest that the cartilage antigenic components released by
      an inflammatory process or trauma may trigger a vicious circle of chronic
      inflammation and joint destruction.

PMID- 9537051
TI  - Failure to demonstrate public idiotypes on cytolytic cells with specificity for
      NP-coupled syngeneic cells.
AB  - We have investigated whether cytolytic cells specific for hapten-coupled
      syngeneic cells have the same public idiotype as serum antibodies against the
      same hapten, NP-aminocaproyl (NP-cap). Anti-NP-cap antibodies of C57BL mice
      possess a public idiotype that can be detected by antisera against the whole V
      region of the antibody molecule or against the VH domain. Neither reagent had an
      effect on the cytolytic response either when they were used to sensitize the
      effector cells for complement killing or when used at high concentrations in the
      culture medium during the secondary stimulation in vitro.

PMID- 9537053
TI  - Determination of the immunoglobulin class of complement-dependent cytotoxic
      antibodies in serum of D23 hepatoma-bearing rats.
AB  - The immunoglobulin class of the complement-dependent cytotoxic antibodies in
      serum from D23 hepatoma-bearing rats (D23 TBS) for D23 hepatoma cells was
      analysed. When studied by affinity chromatography with concanavalin A, protamine,
      or staphylococcal protein A conjugated to Sepharose, the cytotoxic activity bound
      to the former two but not protein A. The binding fractions were further
      characterized by column chromatography on Sepharose CL-4B. The cytotoxic activity
      was recovered exclusively in the high molecular weight fractions corresponding to
      human IgM. Monitoring with IgG- or IgM-specific rabbit antibodies indicated that
      these high molecular weight cytotoxic fractions contained both IgG and IgM.
      However, fractionation of D23 TBS at low pH suggested that cytotoxicity was due
      to IgM antibodies rather than to immune-complexed IgG antibodies. This was
      supported by the findings that rabbit antirat IgM antibodies inhibited the
      cytotoxicity of TBS completely when added at high dilutions.

PMID- 9537054
TI  - The ultrastructure of the tubular complex in the cytoplasm of cytolytic T
      lymphocytes.
AB  - The DNA synthesis, the cytolytic activity, and the ultrastructure of cytolytic T
      lymphocytes (CTL) derived from mixed mouse thymocyte culture on day 5 were
      studied. CTL of thymic origin were absorbed by centrifugation on the surface of
      target cell (TC) monolayers. At different time intervals after absorption, single
      tubular structures (TS) and complex of tubular structures (CTS) linked with
      ergastoplasmic reticulum, secretory granules, Golgi apparatus, coated vesicles,
      and multivesicular bodies were detected in the CTL cytoplasm. The linkage of CTS
      with ergastoplasmic reticulum, ribosomes, and secretory lymphocyte mechanism
      suggests the possibility of a secretory-receptor mechanism of TC cytolysis. The
      release of numerous secretory vacuoles was accompanied by the enlargement of the
      cytoplasmatic lymphocyte membrane surface, which seemed to cause its shedding.
      'Membranosomas' were observed on CTL membrane; their role is still obscure and
      awaits further study.

PMID- 9537055
TI  - The influence of serum on random migration and chemotaxis of polymorphonuclear
      leucocytes: methodological evaluation using sera from infection-prone patients
      and normals.
AB  - The effects on normal polymorphonuclear leucocytes (PMN) of chemotactic and
      chemokinetic factors in sera from normal subjects and infection-prone patients
      were examined by means of the leading-front technique, using a modified Boyden
      chamber. The analysis scheme used made it possible to differentiate between
      chemotactic and chemokinetic factors and demonstrated that different factors
      account for the major chemotactic and chemokinetic activities of serum. The major
      chemotactic activity of unactivated serum was heat-labile, and the chemotactic
      activity of factor XII-deficient sera was normal, suggesting the major
      chemotactic activity to be distinct from C5a and factor XII-dependent pathways.
      The existence of both heat-stable and heat-labile chemokinetic factors was shown.
      The possibility that the reduced chemokinetic effect of several patient sera was
      caused by abnormal levels of the serum proteins alpha 1-antitrypsin, alpha 2
      macroglobulin and albumin was excluded.

PMID- 9537056
TI  - Spontaneous plaque-forming human lymphocytes detected with the protein-A plaque
      assay.
AB  - A sizable proportion of fresh human blood and adenoid lymphocytes were found to
      produce antibodies when tested in the protein-A plaque assay of Gronowicz et al.
      Plaque formation was not caused by release of passively adsorbed immunoglobulin
      but depended on active immunoglobulin secretion. We have investigated optimal
      conditions for plaque formation in this test system. Good reproducibility is
      obtained only if cells to be tested are kept in the cold before assay, since the
      antibody-forming capacity of these cells is rapidly exhausted at temperatures
      above 2 degrees C. In blood lymphocytes the number of IgA-producing cells exceeds
      those of IgG and IgM, whereas in the adenoid IgG plaque-forming cells dominate.
      Studies on the use of this method for the monitoring of immune responses are in
      progress.

PMID- 9537057
TI  - Suppressor cells and their precursors in A/J mice, tolerant to heterologous gamma
      globulin.
AB  - The role of suppressor cells and of their precursors was examined in A/J mice,
      immunized or tolerized-immunized with rabbit gamma globulin. Antibody response
      and tolerance were assessed by antigen elimination, followed by an indirect
      plaque-forming assay. Reconstitution experiments were performed to estimate loss
      of cooperative capacity in thymus and spleen cells. Infectious tolerance was
      examined by reconstitution with mixtures of spleen or thymus cells of normal and
      tolerant donors. Infectious tolerance could not be detected after neonatally
      induced tolerance. It could be detected when tolerance was induced 11-16 days
      after birth. Under these circumstances, loss of cooperative capacity and
      increased capacity for infectious tolerance occurred rapidly over the first 2
      days and reached completion by the 10th-20th day after administration of
      tolerogen. Thymectomy, after tolerance induction, resulted in relative recovery
      of responsiveness of spleen cells and loss of capacity for infectious tolerance.
      Pretreatment with cyclophosphamide resulted in a less profound state of
      unresponsiveness and in the disappearance of the capacity for infectious
      tolerance. Simultaneous treatment with tolerogen and colchicine also resulted in
      a less profound state of tolerance. This effect of colchicine was more profound
      when a low dose of tolerogen was used or when animals were thymectomized before
      administration of tolerogen and colchicine.

PMID- 9537058
TI  - Expression of HLA-ABC and -DR locus antigens on human kidney, endothelial,
      tubular and glomerular cells.
AB  - The distribution of the major histocompatibility complex antigens on the various
      cellular structures of the human kidney was analysed by using a modified
      Staphylococcus aureus Cowan 1 method. Conventional alloantisera and heterologous
      antisera raised against isolated molecules were used for the HLA-ABC antigens,
      whereas the HLA-DR (Ia) antigens were detected with heterologous antisera only.
      The HLA-ABC antigens were expressed on all types of kidney passenger leucocytes,
      on vascular endothelial cells, and on kidney tubular cells, but not substantially
      on the glomerular podocytes. The DR antigens were strongly expressed on (a
      fraction of) the passenger lymphocytes and on the kidney vascular endothelial
      cells, weakly on the passenger monocytes, but not measurably on the urine
      producing apparatus of the kidney--that is, on the glomerular and tubular cells.

PMID- 9537059
TI  - The fetus as an allograft: a longitudinal study of normal human pregnancies
      studied with mixed lymphocyte cultures between mother-father and mother-child.
AB  - A longitudinal investigation of the mixed lymphocyte culture (MLC) response
      during pregnancy between mother and father, between mother and child, and between
      the mother and an indifferent lymphocyte pool has been carried out, using
      starting values before pregnancy and a cryobiological freezing system that allows
      in vitro playback of the immunological course of pregnancy. Lymphocyte and serum
      samples from twenty-two pregnant women taken before and during pregnancy, at
      delivery, and after delivery were used. The study shows that the mother reacts
      during the course of pregnancy with an increasing MLC response to the father,
      which is replaced at delivery by a decrease in response and a subsequent increase
      after delivery. It is also shown that the mother reacts to the child in a similar
      manner at about half the level of reaction to the father. The mother also reacts
      similarly to a pool of indifferent lymphocytes. The MLC reactions mentioned are
      affected by both non-pregnant and pregnant serum, leading to a moderation of the
      MLC reaction in relation to that carried out in neutral AB serum. In addition,
      there seems to be cooperation between cellular and humoral factors, since the MLC
      reaction to the child carried out in relevant autologous serum seems to show a
      decreasing response during the course of pregnancy, in accordance with increasing
      tolerance of the fetal allograft.

PMID- 9537060
TI  - Lymphocyte transformation with mitogens and antigens during normal human
      pregnancy: a longitudinal study.
AB  - In a longitudinal analysis of immunological changes in normal human pregnancy,
      twenty-two pregnant women were studied, with blood samples taken before
      pregnancy, during its course, at delivery, and 3-5 months after delivery. The
      blood samples were frozen successively, using a cryobiological freezing system,
      and were stored until the whole longitudinal series was obtained. The collected
      material for a longitudinal series was then thawed and tested in one seance.
      Lymphocyte transformation tests were performed with stimulation with the mitogens
      phytohaemagglutinin (PHA), pokeweed mitogen (PWM), concanavalin A (Con A) and the
      specific antigens tuberculin purified protein derivative (PPD), Candida albicans
      (CA), Staphylococcus aureus (SA) and streptokinase/streptodornase (SK/SD). No
      changes were found in PHA or in PWM responses, whereas there were significant
      changes in the Con A response, with lowest values in the middle of pregnancy.
      PPD, CA, SA and SK/SD responses all reached lowest values towards the end of
      pregnancy, with increases subsequently, after delivery. These findings seem to
      show that T suppressor function is increased and B-lymphocyte function decreases
      during the course of pregnancy.

PMID- 9537061
TI  - Antigen-initiated B-lymphocyte differentiation. XVII. The inhibitory effects of
      recent antigen prepriming on the subsequent responsiveness of 'pre-progenitor' B
      cells.
AB  - We have analysed the transient unresponsiveness of B cells following specific
      antigen prepriming. The effect is restricted to adoptive-transfer antibody
      forming cell (AFC) progenitors (that is, 'pre-progenitors') and does not occur
      with the separate subset of cell culture AFC progenitors ('direct progenitors').
      The transient unresponsiveness is displayed by both primary and secondary 'pre
      progenitor' B cells. Mixing experiments and experiments with athymic mice
      indicate that the effect is not due to suppressor T cells or other inhibitory
      cells. Nor is the effect due to an impaired seeding ability of the activated or
      antigen-binding cells, since after adoptive transfer the preprimed cells can be
      activated by an appropriate non-specific stimulus. The most likely explanation
      involves direct interaction of specific antigen with the antigen receptors on
      'pre-progenitor' B cells, rendering these cells more prone to temporary or
      permanent 'tolerance' on further antigen contact or, alternatively, directing
      their differentiation away from IgM AFC production on day 8 after transfer.

PMID- 9537062
TI  - Effect of long-term corticosteroid therapy on monocyte chemotaxis in man.
AB  - The influence of prednisolone on monocyte chemotactic activity in vitro at
      prednisolone concentrations comparable with those achieved in man following oral
      dosage has been investigated. Chemotactic activity of monocytes from each of
      sixteen normal subjects was suppressed by concentrations of prednisolone as low
      as 25 ng/ml (suppression of chemotaxis, 20%). Maximal suppression occurred at 100
      ng/ml (suppression of chemotaxis, 48%) and no significant increase in suppression
      was produced by increasing the concentration to 200 ng/ml (suppression of
      chemotaxis, 53%). In contrast, monocytes isolated from ten patients receiving
      corticosteroid therapy showed no significant suppression of chemotactic activity
      when exposed to these concentrations of prednisolone, even though they exhibited
      a normal ability to respond to a chemotactic stimulus. The lack of suppression of
      monocyte chemotaxis in patients receiving corticosteroid therapy is unexplained,
      but may represent a change in the circulating monocyte or lymphocyte populations.

PMID- 9537063
TI  - Distribution of 'free' and HLA-associated human beta 2-microglobulin in some
      plasma membranes and biological fluids.
AB  - The distribution of free and HLA-associated human beta 2-microglobulin (beta 2m)
      in serum, urine, spinal fluid, parotid duct saliva, seminal fluid, amniotic fluid
      and whey and in membranes from thrombocytes, lymphocytes, neutrophils and fat
      globules from milk was studied by crossed radioimmunoelectrophoresis (CRIE). The
      hydrophobic domain of HLA was demonstrable in 'charge-shift CRIE' and by binding
      to phenyl-Sepharose in 'hydrophobic-interaction CRIE'. In 'lectin-affinity CRIE'
      with concanavalin A and Lens culinaris lectin Sepharose the carbohydrate moiety
      present on. HLA exhibited heterogeneity as judged by the appearance of two partly
      separated protein peaks. Except for isolated fat globule membranes, HLA
      associated beta 2m was present on all cells investigated. 'Free' beta 2m did not
      contain a hydrophobic domain as assessed by charge-shift and hydrophobic
      interaction CRIE. All body fluids contained beta 2m in its 'free' form only. In
      serum, besides the free beta 2m, 2% was present as HLA-associated beta 2m, which,
      however, did not contain a hydrophobic domain. A degradation product of 'free'
      beta 2m, with alpha-mobility, was observed in sera from patients with malignant
      disorders, rheumatoid arthritis or systemic lupus erythematosus.

PMID- 9537064
TI  - The Isopaque-Ficoll method re-evaluated: selective loss of autologous rosette
      forming lymphocytes during isolation of mononuclear cells from human peripheral
      blood.
AB  - A subpopulation of lymphocytes is defined, which--under conditions used for
      isolating mononuclear cells from peripheral blood by the Isopaque-Ficoll gradient
      -is lost to the erythrocyte pellet because of rosette formation with the
      autologous erythrocytes in the gradient. Reapplication of the resuspended
      erythrocyte pellet on a new gradient with higher density could, however, recover
      the subpopulation. Lymphocyte surface marker analysis on such cells showed that
      they were enriched in T cells (judged by rosette formation with sheep
      erythrocytes) and in autorosette-forming cells. The importance of these findings
      is discussed in relation to the wide use of the Isopaque-Ficoll method.

PMID- 9537065
TI  - Effect of Fc-receptor modulation on mumps-virus-dependent lymphocyte-mediated
      cytotoxicity in vitro.
AB  - The natural cytotoxicity of peripheral blood lymphocytes (PBL) from normal human
      donors to a variety of tissue culture target cells increases upon brief exposure
      of lymphocytes to mumps virus. The effector cells operative in this system have
      Fc receptors for IgG (FcR), since cytotoxicity was abolished when FcR+ cells were
      removed by passage of the lymphocyte over immune-complex columns. When PBL were
      treated with immune complexes for 16 h at 37 degrees C, their FcR activity was
      sharply decreased (modulation), as indicated by a significantly reduced capacity
      of the treated cells to display antibody-dependent cytotoxicity (ADCC).
      Modulation had variable effects on natural cytotoxicity. In contrast, the virus
      dependent cytotoxicity above the natural cytotoxicity remained essentially
      unchanged, indicating that a functionally intact FcR is not required in this
      system for carrying out cytolysis.

PMID- 9537066
TI  - [Hormonal disruptors and farm animals].
AB  - A number of man made environmental contaminants displays a weak hormonal, usually
      oestrogenic, activity. Currently such contaminants are termed hormone disruptors,
      a terminology that also includes natural compounds with hormonal activity, such
      as phyto and fungal oestrogens. Fertility and morphological defects in wildlife
      are related to high exposure to man made hormone disruptors. The potential threat
      of such exposure for human reproductive health is widely discussed. A possible
      decline in sperm counts in men is one of the subjects related to such
      environmental factors. There are no firm indications for this threat. Additional
      research is needed, however, for a more complete assessment. Farm animals so far
      played a minor role in the discussion. Therefore, in a study published elsewhere,
      long term trends in sperm counts of Dutch Dairy Bulls have been evaluated (27).
      No decline was found in 75,238 ejaculates collected between 1977 and 1996 from
      2,314 bulls of the centre for artificial insemination (AI) NOORDWEST. Results of
      this study, published elsewhere, formed the reason to broader go into the
      relation between hormone disruptors and farm animals, observed effects of phyto
      oestrogens in such animal and the role these animals could play in further
      research.

PMID- 9537067
TI  - [Gumboro vaccination].

PMID- 9537068
TI  - [Pioneers: veterinarians from earlier times (25). William Youatt (1776-1847)].

PMID- 9537069
TI  - [Veterinary Disciplinary Tribunal].

PMID- 9537071
TI  - [Report of a study day on xenotransplantation. The patient looks for his own
      health].

PMID- 9537070
TI  - [Annual report BBD (Bureau Adverse Effects Veterinary Drugs): a synopsis].

PMID- 9537072
TI  - [Surgical treatment of an obliterating thrombosis of the jugular vein in a horse.
      Use of synthetic vessel prosthesis].
AB  - A 6-year-old trotter gelding presented with exercise intolerance and swelling of
      the left side of the head during exercise and grazing. The complaints were caused
      by a complete thrombosis of the left jugular vein. In this case report a surgical
      approach is described in which a bypass was created with a synthetic vascular
      graft. After treatment the horse was capable of racing at his former level. The
      patency of the synthetic graft was 11 months.

PMID- 9537073
TI  - [Amyloidosis, a current problem].

PMID- 9537074
TI  - [Amyloidosis in cats: a genetic problem?].

PMID- 9537075
TI  - [Veterinary Disciplinary Tribunal].

PMID- 9537076
TI  - [Mutual recognition: experiences and problems in various countries].

PMID- 9537077
TI  - [Hog cholera crisis].

PMID- 9537079
TI  - [Hog cholera crisis center].

PMID- 9537081
TI  - [Dimethylsulfoxide (DMSO) in horses: a literature review].
AB  - The use of dimethyl sulphoxide in equine medicine is discussed with special
      reference to trauma of the central nervous system, chronic endometritis, trauma
      of the locomotor apparatus, and ischaemic bowel pathophysiology. The ability of
      dimethyl sulphoxide to reduce connective tissue formation might be of interest in
      abdominal surgery. The anti-inflammatory effect of dimethyl sulphoxide is used in
      the treatment of muscle trauma, tendinitis, laminitis, and arthritis. Dimethyl
      sulphoxide can potentiate the effects of other drugs. The most common dose is 1
      g/kg body weight intravenously up to a 40%-solution with a maximum duration of
      treatment of 5 days. Dimethyl sulphoxide has not been approved for use in horses
      in the Netherlands.

PMID- 9537082
TI  - [Apex resection in horses].

PMID- 9537083
TI  - [Pigs possibly are a source of Mycobacterium avium infections in man].

PMID- 9537084
TI  - [Uterine defense mechanisms in horses. Function of the cervix and the
      myometrium].

PMID- 9537085
TI  - [Electronic identification offers new perspectives. Road from veterinarian to
      passport cut off].

PMID- 9537086
TI  - [Spread of an intramuscularly administered live gE-negative BHV1 marker vaccine
      in 2 cattle farms].
AB  - Cattle are vaccinated with a live gE-negative BHV1-marker vaccine as a part of a
      programme to eradicate bovine herpes virus 1 in the Netherlands. To investigate
      whether this vaccine is transmitted to unvaccinated cattle in a herd after
      intramuscular administration, cattle from two herds were vaccinated: of a herd of
      114 BHV1-antibody negative cattle on one farm, 45 animals were vaccinated, and of
      a dairy herd of 55 cattle in another farm, all 10 BHV1-positive animals were
      vaccinated. Vaccination was repeated after about a month. Antibodies against BHV1
      were determined in all unvaccinated cattle to detect potential BHV1-antibody
      responses. Only one unvaccinated cow (from the dairy herd) showed BHV1
      seroconversion. However, this antibody response was detected by a gE-ELISA as
      well as by a gB-ELISA. This indicates that the animal was infected by a field
      virus and not by the gE-negative vaccine virus. Thus intramuscularly administered
      live gE-negative BHV1 marker vaccine did not spread to unvaccinated cattle (n
      =154) on two farms.

PMID- 9537087
TI  - [Mastitis following drying up associated with teat wipes contaminated with
      Pseudomonas aeruginosa].
AB  - On 6 Dutch dairy farms cows died of an acute, very serious mastitis caused by
      Pseudomonas aeruginosa. This happened shortly after drying off with antibiotics.
      Before drying off the teat ends were cleaned with teat wipes contaminated with
      Pseudomonas aeruginosa.

PMID- 9537088
TI  - [Pustular dermatitis in veterinarians following delivery in farm animals; an
      occupational disease].
AB  - OBJECTIVE: To assess the prevalence of contact dermatitis after deliveries in
      cattle or sheep among veterinarians. DESIGN: Retrospective. SETTING: Provinces of
      Groningen, Friesland, and Drenthe, The Netherlands. METHODS: By means of a short
      inquiry 310 veterinarians were asked whether and how often they had experienced
      pustular dermatitis after deliveries in cattle and sheep and what course the
      dermatitis had run. They were also asked about details of the deliveries (type of
      animal, condition of the foetus, course of the partus), about microbiological
      investigation, preventive measurements and therapy. RESULTS: The response to the
      questionnaires was 24.5%. One or more episodes of pustular dermatitis on an arm
      after a delivery in cattle or sheep was noticed by 62 (81.5%) of the 76
      respondents. Sometimes it was associated with secondary symptoms like headache,
      fever and lymphadenitis. Listeria monocytogenes (7 times out of 13) and
      Salmonella dublin (4/13) were the agents cultured most often. CONCLUSION: Contact
      dermatitis after deliveries in cattle or sheep occurs frequently as an
      occupational disease of veterinarians.

PMID- 9537089
TI  - [Integrated approach to animal health essential].

PMID- 9537090
TI  - [Veterinary Disciplinary Tribunal].

PMID- 9537091
TI  - [A method of evaluating stallion sperm].

PMID- 9537092
TI  - [Nutrition more important in the treatment of chronic kidney insufficiency in
      dogs].

PMID- 9537093
TI  - [Commotion concerning evaluation hog cholera control. Unjust portrayal of
      veterinarian in media].

PMID- 9537095
TI  - [Acute blindness due to trauma in a Welsh pony-colt].
AB  - A healthy, 10-day-old Welsh A pony colt was totally blind 1 day after arrival at
      a studfarm. Both eyes appeared normal on external inspection. The young animal
      had been very distressed during the 40-km journey to the studfarm. Intravenous
      corticosteroids were administered for 2 days, but did not result in any
      observable improvement. The animal was euthanized at the owner's request. Both
      eyes with the optic nerves were removed for histological examination. Both optic
      nerves showed Wallerian degeneration, a well-known response of peripheral nerves
      to trauma. The foal, which was not tethered during transportation, probably
      sustained a blunt trauma in the trailer. This case highlights the importance of
      taking adequate measures to prevent young animals from sustaining blunt trauma
      during transport.

PMID- 9537096
TI  - [A good snare for the pig sector].

PMID- 9537097
TI  - [Detection of hyperketonemia with the aid of monitoring milk production and two
      milk tests].
AB  - In addition, it is relevant to know to what extent milk production data can
      provide information about hyperketonaemia. In 12 selected herds, milk samples
      were collected from 114 cows that had been lactating for maximally 70 days.
      During regular milk testing, two additional milk samples were taken to assess the
      'Nitroprusside test' and the 'Ketolac BHB' test. After collection of milk
      samples, blood samples were taken to measure serum beta-hydroxybutyric acid. The
      prevalence of hyperketonaemia appeared to vary between herds from 1 to 9 per 10
      lactating cows. The sensitivity of the Nitroprusside test was higher than the
      sensitivity of the Ketolac BHB test at threshold values of beta-HBA > 1.5 mmol/l.
      The Ketolac BHB test in comparison to the Nitroprusside test appeared to provide
      a smaller chance of false-positive test results at a given level of sensitivity.
      The serum beta-hydroxybutyric acid concentration was correlated with milk
      yield/day and the milk fat concentration of an individual cow.

PMID- 9537098
TI  - [Pioneers: veterinarians from earlier times (26). Alexander Numan (1780-1852)].

PMID- 9537099
TI  - [Professor in animal rights is a many-sided person. Interview by Sophie Deleu].

PMID- 9537100
TI  - [Group housing in pig farming].

PMID- 9537102
TI  - [Team work relationship of companion animal practices and veterinarian's role in
      intracommunal trade].

PMID- 9537105
TI  - [Introduction of BHV1 on dairy farms. Risk assessment by cattle farmers and
      veterinarians].
AB  - A study is being carried out at Wageningen Agricultural University together with,
      among others, the Animal Health Service to determine the possibilities and
      economic consequences of a more closed farming system for (Dutch) dairy farms.
      Three identical workshops, held in the evening, were organized as part of the
      study. The opinion of farmers and their veterinarians on the importance of risk
      factors for the introduction of diseases on a farm was determined, using Bovine
      Herpes Virus type 1 (BHV1) as an example. In total, 27 farmers and 13
      veterinarians participated in the workshops and completed a computerized
      questionnaire that was based on Adapted Conjoint Analysis (ACA). The results of
      the farmers and veterinarians were compared. Both farmers and veterinarians
      seemed well aware of the risk of direct animal contacts for introduction of BHV1.
      Farmers thought visitors to be of more risk than veterinarians. By making use of
      information obtained from the ACA workshops, it will be possible to improve the
      advice given to different groups in the dairy sector.

PMID- 9537106
TI  - [Clinical aspects of fertility in stallions].
AB  - The studies described in this thesis investigated the factors that can affect the
      fertility of stallions. The introduction describes the male gamete and the
      processes that occur during maturation of sperm and fertilization. Methods to
      evaluate the quality of sperm and ova are then discussed. Fertility can be
      expressed in various ways and is also affected by many factors such as the
      stallion, the mare and management factors. The fertility of stallions is usually
      assessed a good year after they have served mares, because then the number of
      foals is known. However, it would be preferable to be able to predict a
      stallion's fertility before he is put to stud. To this end, it was investigated
      whether there is a relationship between a number of sperm parameters and the
      percentage of non-return after the first cycle. The endocrine control of
      reproduction is briefly described because hormonal factors can also influence the
      reproductive potential of stallions. The venereal diseases that are important for
      regulations concerning the international trade in sperm are also described. The
      relevance of this diseases to reproduction deserves further investigation. The
      minimum requirement for a stud stallion is that the stallion should produce sperm
      of adequate quality and should be able to fertilize mares.

PMID- 9537107
TI  - [Milk cell count and mastitis].

PMID- 9537108
TI  - [Change in welfare demands for calves according to EC guidelines. European
      Community].

PMID- 9537109
TI  - [Promotion of interests of practitioners].

PMID- 9537110
TI  - [Use of antibiotics in horses].

PMID- 9537111
TI  - Atrial fibrillation.

PMID- 9537113
TI  - Cognitive-behavioral therapy.

PMID- 9537112
TI  - What should a man weigh?

PMID- 9537114
TI  - Sex and survival: good news at last?

PMID- 9537115
TI  - I'm troubled by recurrent fever blisters. They seem to come on anytime, even if I
      don't have a cold. Is there anything I can do to prevent them?

PMID- 9537117
TI  - Health tips. Recognizing warning signs of a stroke.

PMID- 9537116
TI  - Insomnia. What to do when you can't get a good night's sleep.

PMID- 9537118
TI  - New diet drug is not without health risks.

PMID- 9537119
TI  - Another volley in the estrogen dose debate.

PMID- 9537120
TI  - Polymyalgia rheumatica. Relief can be dramatic.

PMID- 9537121
TI  - Outpatient surgery. Planning ahead helps.

PMID- 9537122
TI  - The DASH diet. It may benefit your blood pressure, and more.

PMID- 9537123
TI  - Is there something I can do to prevent bone loss if I'm taking steroids
      regularly?

PMID- 9537124
TI  - My cholesterol is normal, but my triglycerides are a little high. My doctor says
      not to worry about it, but aren't triglycerides as important as cholesterol?

PMID- 9537125
TI  - Are we getting better at treating retinal detachment? Technology, referral
      pattern or primary care?

PMID- 9537126
TI  - Antimetabolites for all?

PMID- 9537127
TI  - The British Ophthalmological Surveillance Unit: the study of uncommon ophthalmic
      disorders made easier.

PMID- 9537128
TI  - How should active toxoplasmic retinochoroiditis be treated?

PMID- 9537129
TI  - The Duke Elder Lecture. Flying blind.

PMID- 9537130
TI  - Do transplanted corneal limbal stem cells survive in vivo long-term? Possible
      techniques to detect donor cell survival by polymerase chain reaction with the
      amelogenin gene and Y-specific probes.
AB  - PURPOSE: To investigate donor cell survival following corneal limbal stem cell
      grafting, which is based on the corneal stem cell model. METHODS: We describe the
      use of the amelogenin gene probe with the polymerase chain reaction (PCR) to
      detect surviving donor cells and report preliminary studies using Y-specific DNA
      probes. RESULTS AND CONCLUSIONS: DNA polymorphisms have a detection limit of 10%.
      The SRY 'Y-specific' probe has a theoretical detection limit of 1 cell in 10,000.
      The techniques were applied to investigate survival of male donor cells in an
      aniridic female patient 2 1/2 years following limbal stem cell grafts. We
      speculate that low levels of donor-derived cells may still be present. We discuss
      the advantages and disadvantages of the two approaches, which may have future
      clinical and experimental application.

PMID- 9537131
TI  - Penetrating keratoplasty in the mentally retarded.
AB  - Penetrating keratoplasty is infrequently performed in the mentally retarded due
      to the high risk of serious post-operative complications, in particular wound
      rupture and severe inflammation of the graft. Graft survival is hindered by the
      patient's tendency for eye rubbing and possibly self-inflicted injury. Adequate
      nursing support is essential to ensure strict compliance with post-operative
      treatment. A retrospective study of corneal graft outcomes in mentally retarded
      patients was undertaken to assess graft survival, visual rehabilitation, post
      operative complications and the influence on social behaviour. Six cases of
      penetrating keratoplasty performed in mentally retarded patients by one surgeon
      are presented. A continuous 10-0 nylon suture was employed in all cases. In 2
      cases surgery was undertaken following perforation of the globe in patients with
      Down's syndrome. The grafts were retained in all cases and 2 patients achieved
      reasonably good acuity, although formal visual acuity assessment in these
      patients is limited. Penetrating keratoplasty in mentally retarded patients is a
      potentially hazardous procedure and patients require close supervision and good
      support care. This series demonstrates that relatively successful outcomes can be
      obtained in some mentally retarded patients.

PMID- 9537132
TI  - Conjunctival autograft versus topical mitomycin C in treatment of pterygium.
AB  - A prospective study was carried out to assess the recurrence rate of pterygium
      with conjunctival autograft versus the use of topical mitomycin C. In 27 eyes
      undergoing pterygium excision with conjunctival autograft, the recurrence rate
      was found to be 25.9% after 1 year mean follow-up. In the second group of 32
      eyes, pterygium was removed using the bare sclera method. All these patients
      received post-operatively 0.2 mg/ml (0.02%) topical mitomycin C twice a day for 5
      days. At 1 year mean follow-up, the recurrence rate in this group was 9.4%.
      Although the difference was not statistically significant, the number of
      recurrences was lower in the mitomycin-C-treated group than in patients
      undergoing conjunctival autograft.

PMID- 9537133
TI  - High-resolution magnetic resonance imaging of the normal extraocular musculature.
AB  - PURPOSE: Magnetic resonance imaging (MRI) of the extraocular muscles has
      attracted growing interest for the evaluation of complex motility disorders.
      However, little information is available on the high-resolution MRI anatomy of
      the normal extraocular muscles and their connective tissue system. The study
      describes the imaging anatomy of the recti and oblique muscles and the levator
      palpebrae superioris muscle. METHODS: MRI of the orbit at 1 tesla was performed
      in four normal volunteers using a surface coil. RESULTS: Many anatomical details
      such as Zinn's tendinous annulus, the trochlea, the superior oblique tendon, the
      intermuscular septa, the check ligaments, Lockwood's ligament and the common
      sheath between the superior rectus muscle and the levator muscle were visualised.
      A striking imaging feature was the curved path of both the recti muscles and the
      levator palpebrae muscle. The inferior oblique muscle also showed a marked
      curvature in the region of Lockwood's ligament. CONCLUSIONS: High-resolution MRI
      is capable of demonstrating the anatomy of the extraocular musculature and parts
      of its connective tissue system. The curved path of the extraocular muscles can
      be explained by the configuration of the orbital connective tissue system which
      couples each extraocular muscle with the adjacent orbital wall. We discuss the
      clinical implications of our findings and review previous radiological studies
      regarding the functional anatomy of the extraocular muscles.

PMID- 9537134
TI  - Cystic schwannoma of the orbit.
AB  - Cystic schwannoma of the orbit is unreported in the world literature. A 54-year
      old Caucasian man presented to our clinic with a 5 year history of progressive
      right-sided proptosis and diplopia. A large paramedian cystic mass displacing the
      right globe downwards and laterally was demonstrated. From the clinical and
      radiological features, the presumptive diagnosis of right frontal sinus mucocoele
      was made. However, the excisional biopsy of the lesion revealed the rare
      diagnosis of cystic schwannoma, arising from a branch of the first division of
      the trigeminal nerve. Post-operatively, the patient had a smooth recovery with
      visual acuity of 20/20 in each eye; full binocular single vision was also re
      established. The differential diagnoses of cystic orbital mass, and the
      radiological and histological findings of the lesion, are described and
      discussed.

PMID- 9537135
TI  - The use of autogenous auricular cartilage in the management of upper eyelid
      entropion.
AB  - Upper eyelid entropion can occur as a consequence of inflammation, infection,
      trauma or surgery. It may very rarely occur as a congenital eyelid malposition.
      Numerous surgical procedures have been described to correct it depending on the
      primary anatomical and pathophysiological defects. We describe the use of
      autogenous auricular cartilage for its correction where the tarsal plate is found
      to be deficient. Seven patients were studied prospectively after correction of
      their upper eyelid entropion with autogenous auricular cartilage with a minimum
      follow-up of 6 months. We report the surgical technique, and the results and
      complications of the procedure.

PMID- 9537136
TI  - Early correction of severe unilateral infant ptosis with the Mersilene mesh
      sling.
AB  - Ten consecutive cases of severe unilateral congenital ptosis were surgically
      corrected before 1 year of age (range 3-11 months) in an attempt to achieve early
      functional and cosmetic improvement. In all cases, a frontalis suspension using
      Mersilene mesh was performed. With a mean follow-up of 40.3 months (range 33-54
      months), all patients achieved normal or near normal eyelid position and all had
      their chin-up head posture resolved. One patient developed a mild exposure
      keratitis that was treated successfully with topical antibiotics and lubricants.
      Our findings suggest that the Mersilene mesh sling has good potential for ptosis
      management in infants who are too young for fascial harvesting. However, a larger
      series with a longer follow-up period is required before the eventual safety and
      efficacy of the Mersilene mesh sling can be properly ascertained.

PMID- 9537137
TI  - Reproducibility of optic nerve head topographic measurements with the glaucoma
      scope.
AB  - PURPOSE: Glaucoma is an optic neuropathy in which optic nerve changes are
      important in diagnosis and progression, because the visual field may remain
      normal even while the optic nerve is undergoing significant damage. Accurate
      methods to objectively document the appearance of the optic nerve are necessary.
      In order for an optic disc imaging system to be clinically useful for detecting
      change, its reproducibility must be established. METHODS: We measured the
      reproducibility of duplicate measurements in 59 eyes of 31 consecutive patients,
      grouped into glaucoma subjects (n = 29) and eyes with glaucoma (n = 30), with the
      3.10 OIS Glaucoma-Scope. In order to simulate two visits on one day, sets of
      three optic disc images were obtained first, followed by a repeat set, and the
      best disc images of each (chosen by the computer) were compared. RESULTS: The
      coefficients of variation of duplicate measurements for glaucoma suspects and
      patients with glaucoma were respectively: vertical cup/disc (c/d) ratio, 6.3% and
      3.47%; horizontal c/d ratio, 4.61% and 2.97%; c/d area, 3.29% and 1.37%; cup
      area, 1.82% and 1.72%; mean position (MP) disc, 13.3% and 10.42%; MP total, 10.1%
      and 13.2%. For three eyes the examination was not possible (opacification of
      posterior capsule, miosis). CONCLUSION: These results suggest that the 3.10
      version of the OIS Glaucoma-Scope allows reproducible measurements in living
      eyes.

PMID- 9537138
TI  - Retrobulbar haemodynamic changes studied by colour Doppler imaging in glaucoma.
AB  - PURPOSE: To determine the effect of spontaneously elevated intraocular pressure
      (IOP) on the ocular circulation, and evaluate the result of IOP-lowering
      procedures in terms of haemodynamics. METHODS: Colour Doppler imaging (CDI) was
      employed to determine the peak systolic velocity (PSV), end-diastolic velocity
      (EDV) and time average maximal velocity (TAMV), as well as the Pourcelot ratio
      (PR) and pulsatility index (PI), of the central retinal artery (CRA), posterior
      ciliary arteries (PCA) and ophthalmic artery. Various CDI parameters of the eyes
      with elevated IOP were compared with those of the clinically healthy fellow eyes
      and the control eyes, separately. Also, data from CDI of glaucoma eyes obtained
      during the period of elevated IOP and then following IOP-lowering procedures were
      compared, deliberately avoiding the influence of glaucoma medications. RESULTS:
      Eyes (n = 12) with elevated IOP showed significantly decreased flow velocities of
      the CRA and significantly increased PR and PI of the nasal and temporal PCA,
      compared with the fellow and control eyes, respectively. Following IOP-lowering
      procedures, the PR and PI of the nasal PCA decreased significantly. CONCLUSION:
      Spontaneously elevated IOP may induce haemodynamic changes in the CRA and PCA,
      but no significant change is identified in the ophthalmic artery. Flow velocities
      tend to decrease while the resistance indices tend to increase with elevated IOP.
      Such haemodynamic changes may reverse following normalisation of IOP.

PMID- 9537139
TI  - Electron microscopy findings on an intraocular lens in the uveitis, glaucoma,
      hyphaema syndrome.
AB  - PURPOSE: To report the electron microscopic findings on an explanted intraocular
      lens in a patient with the uveitis, glaucoma, hyphaema syndrome. METHODS:
      Scanning and transmission electron microscopy were undertaken on a coccoon of
      cellular material from the tip of the intraocular lens haptic. RESULTS: Scanning
      electron micrographs showed densely packed coccoid-like structures on the haptic
      surface. By transmission electron microscopy these structures proved to be
      melanosomes. CONCLUSIONS: The scanning electron micrographs described in this
      report are similar to those reported in patients with chronic post-operative
      uveitis, but to our knowledge have not been shown before in association with the
      uveitis, glaucoma, hyphaema syndrome. Transmission electron microscopy determined
      that the coccoid-like structures were melanosomes. The melanosomes are probably
      derived from damaged pigment epithelial cells or iris stromal melanocytes
      secondary to recurrent chafing of the haptic against the posterior surface of the
      iris.

PMID- 9537140
TI  - Gonioscopic laser sclerostomy versus filtration surgery in a rabbit model.
AB  - In a prospective and randomised study, we compared the course of pulsed dye laser
      ab interno sclerostomy with the course of posterior lip sclerectomy in 25
      rabbits. One eye of each rabbit was randomly selected to be treated with laser;
      the fellow eye underwent posterior lip sclerectomy. Intraocular pressure (IOP)
      determinations and slit lamp examinations were recorded pre-operatively, then
      every other day for 3 weeks on 21 of the rabbits. Histological examination was
      performed on the eyes of 3 randomly selected rabbits that were killed 72 hours
      post-operatively. Laser sclerostomy resulted in an average maximal drop in IOP of
      9.5 mmHg on post-operative day 1, and posterior lip sclerectomy resulted in a
      similar drop of 10.5 mmHg (p = 0.43, t-test). By life-table analysis, 88% of eyes
      returned to within 2 mmHg of pre-operative IOP values within 7 days following
      either laser internal sclerostomy or posterior lip sclerectomy. There was no
      significant difference between laser internal sclerostomy and posterior lip
      sclerectomy eyes with respect to the number of days needed to return to within 2
      mmHg of preoperative IOP values (p = 0.26, sign test of the life-table analysis).
      Pulsed dye laser internal sclerostomy appears to be as effective as posterior lip
      sclerectomy in lowering IOP in the rabbit model.

PMID- 9537141
TI  - The clinical presentation of children with tumours affecting the anterior visual
      pathways.
AB  - PURPOSE: To review the ways in which children with tumours affecting the anterior
      visual pathways present and to determine the extent of visual loss at
      presentation and the visual prognosis after treatment. METHODS: A retrospective
      review of the 17 children (age 1-13 years at presentation) referred to a
      specialist paediatric oncology unit. Ten children had extrinsic tumours affecting
      the chiasmal area whilst 7 had intrinsic gliomas affecting the optic nerve and/or
      chiasm. Patients were followed up for up to 13 years (median 2 years). RESULTS:
      The children studied presented with a variety of symptoms including headaches,
      lethargy and growth failure. Despite the clinical finding of marked visual loss
      in several cases, visual failure was not prominent amongst the presenting
      symptoms. After surgical intervention and other treatment vision stabilised or
      improved; eyes with no perception of light for short periods could regain
      substantial vision. CONCLUSION: Children with progressive visual deterioration
      due to tumours do not readily verbalise their difficulty and may have profound
      loss at presentation. Standard clinical tests of vision will identify the extent
      of damage. Visual prognosis depends on the underlying pathology and length of
      history but prompt treatment may lead to substantial improvement in vision.

PMID- 9537142
TI  - Paediatric cycloplegia: a new approach.
AB  - BACKGROUND: Cycloplegia is a traumatic experience for most children, as guttae
      cyclopentolate stings on instillation into the conjunctival sac. This may result
      in inadequate cycloplegia, difficulty in further examination and a child who is
      scared of both the doctor and the ophthalmology department. Guttae proxymetacaine
      hydrochloride 0.5% (Ophthaine, Proparacaine) is a topical local anaesthetic that
      does not sting on instillation. METHODS: Eighty-eight consecutive children in the
      paediatric clinic were assessed. The response of the patient to previous use of
      cyclopentolate alone was assessed by the parents of the child using a grading
      scheme. The use of proxymetacaine prior to instillation of cyclopentolate was
      then assessed using the same grading system. RESULTS: Seventy per cent of the
      children who received cyclopentolate alone were assessed to have cried and been
      unhappy. Ninety-one per cent of the children who received cyclopentolate after
      proxymetacaine were assessed to have shown no adverse reaction to the cycloplegia
      and remained happy. CONCLUSION: This study shows that use of proxymetacaine prior
      to cyclopentolate results in atraumatic cycloplegia in children. This can confer
      multiple benefits on the doctor-patient relationship.

PMID- 9537143
TI  - The value of pre-operative investigations in local anaesthetic ophthalmic
      surgery.
AB  - This study was performed to assess the value of routine investigations performed
      on ophthalmic patients undergoing local anaesthetic surgery. Patients attending
      the pre-operative assessment had investigations ordered as outlined in accordance
      with the guidelines of the Joint Working Party on Anaesthesia in Ophthalmic
      Surgery. The results of investigations were sealed in a clearly marked envelope
      and stapled to a prominent position on the notes. Any envelopes found unopened at
      the end of surgery were assumed to have been unseen by either the anaesthetist or
      surgeon. The effects on patient management were noted. Abnormal results were
      found in 102 of 314 investigations performed in 100 patients. Of the 100
      envelopes 95 were unopened at the end of surgery. No patients had their peri
      operative management changed because of the investigations performed. An adequate
      pre-operative assessment with a history and examination is sufficient in most
      patients undergoing local anaesthetic ophthalmic surgery, avoiding unnecessary
      investigations.

PMID- 9537144
TI  - Discharging routine phacoemulsification patients at one week.
AB  - The reduction of surgically induced astigmatism and rapid refractive
      stabilisation after phacoemulsification have been well studied and often lead to
      reduced follow-up. In this prospective study we reviewed a cohort of 100 patients
      discharged with a refractive prescription at their 1 week post-operative
      appointment following routine sutureless phacoemulsification through a corneal or
      scleral section. The aim was to assess the incidence of late pathology and need
      for review. Eighty-eight patients attended for review between 3 and 4 months post
      operatively, of whom 8 (9.1%) who had been symptomatic had already visited
      ophthalmic casualty. Nine (10.2%) benefited from the follow-up appointment: 4
      were given a new refractive prescription that increased their Snellen visual
      acuity by 1 line; the other 5 were all symptomatic or had incidental findings. We
      feel that provided there is easy access to the eye department, early discharge
      with or without refraction is justifiable as those with surgically related
      pathology at any stage are symptomatic.

PMID- 9537145
TI  - Clinical assessment of a hand-held automated keratometer in cataract surgery.
AB  - PURPOSE: Pre-operative keratometry was performed on 32 eyes of 32 patients
      undergoing extracapsular cataract extraction with intraocular lens implantation,
      for calculation of intraocular lens power. In an additional 20 eyes of 20
      patients post-operative keratometry was performed to guide selective suture
      removal. Readings from a manual keratometer and an automated hand-held
      keratometer were compared. METHODS: Pre-operative measurements were repeated
      three times on each subject to assess the repeatability of each machine. Mean
      difference plots were performed to define the limits of agreement of the two
      machines. RESULTS: Repeatability was higher using manual keratometry (MK) than
      automated keratometry (AK). There was broad agreement between the two machines in
      pre-operative and post-operative assessment, although clinically significant
      differences are likely to occur in some cases. CONCLUSIONS: MK should continue to
      be used for routine pre-operative keratometry, with the AK providing a useful
      alternative when MK is not possible. AK is sufficiently accurate to allow its use
      in post-operative assessment of suture-induced astigmatism.

PMID- 9537146
TI  - A comparison of topical anaesthesia and retrobulbar block for cataract surgery.
AB  - It is possible to remove a cataract and insert an intraocular lens under topical
      anaesthesia (lignocaine 4% preservative-free eye drops) with a van Lint block.
      This study was performed to evaluate this anaesthetic technique. Nineteen
      patients having cataract surgery with topical anaesthesia and a van Lint block
      were compared with 21 patients who received a retrobulbar block and a van Lint
      block. There were no significant differences between the two groups in patient
      characteristics, mean cardiovascular stress of the procedure, experience of pain
      during the operation or willingness to have the same anaesthetic technique again.
      Topical anaesthesia with a van Lint block is feasible for cataract surgery and is
      potentially safer than other regional anaesthetic techniques.

PMID- 9537147
TI  - Trauma-induced Acinetobacter lwoffi endophthalmitis with multi-organism
      recurrence: strategies with intravitreal treatment.
AB  - Endophthalmitis and its treatment are challenging, controversial subjects. We
      report here a patient whose recurrent endophthalmitis required several modes of
      treatment.

PMID- 9537148
TI  - Why are new patients coming to the eye clinic? An analysis of the relative
      frequencies of ophthalmic disease amongst new patients attending hospital eye
      clinics in two separate locations.
AB  - We have analysed 64,417 patient-attendances by 56,409 patients to a dedicated
      ophthalmic new patient service to assess the demographic and epidemiological
      parameters of this population. Forty-three point five per cent were male and
      56.5% female. Nine per cent of patients were under 16 years of age while 27.5%
      were over 70 years. Comparison of patients attending an outreach new patient
      clinic with that at the main hospital showed that a higher proportion of patients
      under 16 years were seen at the outreach clinic (p < 0.001), whereas the main
      clinic saw a higher proportion of patients in the 16-69 year age group (p <
      0.001).

PMID- 9537149
TI  - Results of primary retinal reattachment surgery: a prospective audit.
AB  - PURPOSE: To define the current success rate of primary retinal detachment repair
      at one centre. METHODS: One hundred and fifty-three consecutive patients
      undergoing surgery for primary retinal detachments over a 6 month period were
      studied prospectively. Data sheets were completed immediately after surgery and
      at final follow-up. One hundred and twenty-seven patients completed 6 months of
      follow-up. Follow-up data on the remainder were obtained from the referring unit
      or directly from the patients by telephone. The term primary success was used to
      describe persisting retinal reattachment after a single operation. Multiple
      logistic regression was carried out to establish factors associated with failure.
      RESULTS: One hundred and twenty-three patients (80%) had persisting retinal
      reattachment after a single procedure. Of the 30 patients who required further
      surgery, in 5 the retina remained detached at final follow-up. The final
      anatomical success rate was 97%. New or missed breaks were the major causes of
      failure of primary surgery. Failure of primary surgery was associated with the
      presence of highly elevated breaks (beta = 0.11, p = 0.03). No other pre
      operative factors appeared to predict failure to reattach the retina.
      CONCLUSIONS: Comparison of these results with those of a previous audit carried
      out at this hospital 23 years ago suggests little improvement in the success rate
      of primary surgery (75% vs 80%). The improvement in final retinal reattachment
      has been rather greater (from 88% to 97%). The major impact of recent technical
      advances in retinal reattachment surgery has been on the success rate of
      reoperations after failed primary surgery.

PMID- 9537150
TI  - Exudative age-related macular degeneration in patients with diabetic retinopathy
      and its relation to retinal laser photocoagulation.
AB  - PURPOSE: To study the relationship between exudative age-related macular
      degeneration and diabetic retinopathy and assess the influence of retinal laser
      photocoagulation for diabetic retinopathy on the occurrence of exudative age
      related macular degeneration. METHODS: Two groups, one of diabetic retinopathy
      patients treated with laser and the other of non-laser-treated diabetic
      retinopathy patients, were studied by means of fundoscopy and fluorescein
      angiography for the presence of exudative age-related macular degeneration.
      RESULTS: Exudative age-related macular degeneration was not observed in 431
      patients treated with laser photocoagulation, and was diagnosed in 3.3% of 151
      non-laser-treated patients. CONCLUSION: Patients treated by laser
      photocoagulation for diabetic retinopathy are less prone to develop the exudative
      form of age-related macular degeneration.

PMID- 9537151
TI  - Lipids and lipoproteins in diabetic adolescents and young adults with
      retinopathy.
AB  - PURPOSE: To compare serum concentrations of lipoproteins and apolipoproteins in
      insulin-dependent diabetic patients with and without retinopathy. METHODS: A
      cross-sectional study was performed on 42 diabetic adolescents and young adults
      with different degrees of retinopathy. The mean +/- SD age of the patient was
      21.1 years (range 12.8-27.9 years); their mean duration of diabetes was 12.3
      years (range 7.1-19.9 years). Their glycosylated haemoglobin (HbA1c) and
      fructosamine were respectively 10.2% (8.2-15.4%) and 280.8 mumol/l (202.1-458.5
      mumol/l). Forty-two diabetics without retinopathy similar to the study population
      as regards age, sex, duration of disease, HbA1c and microalbuminuria values, and
      42 healthy subjects, served as controls. RESULTS: Serum lipid and lipoprotein
      concentrations were not different from those of healthy controls in patients
      either with or without retinopathy. The diabetic patients were subdivided in two
      groups according to the degree of their retinopathy: background and
      preproliferative/proliferative retinopathy. Patients with
      preproliferative/proliferative retinopathy were found to have significantly
      higher lipoprotein (a) values than the other group (background, 73.3 IU/l;
      preproliferative/proliferative, 205.9 IU/l; p < 0.001). CONCLUSION: The increase
      in lipoprotein (a) levels might play a role in the development of severe
      retinopathy.

PMID- 9537152
TI  - Optic atrophy in Wolfram (DIDMOAD) syndrome.
AB  - Wolfram syndrome is the association of diabetes mellitus and optic atrophy, also
      called DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy and
      deafness). Incomplete characterisation has caused diagnostic confusion; we
      therefore undertook a nation-wide cross-sectional case finding study. We
      identified 45 patients with Wolfram syndrome, median age 29 years. All patients
      fulfilled the ascertainment criteria (juvenile onset diabetes mellitus and optic
      atrophy). Optic atrophy presented in 38 patients with reduced visual acuity and
      colour vision defect (median age 11 years), progressing to visual acuity of 6/60
      or less in 35 patients (median time 8 years, range 1-25 years). Visual field
      examinations recorded before acuity deteriorated showed central scotomas with
      peripheral constriction. Blind patients had absent pupillary reflexes. Horizontal
      nystagmus was seen in patients with other signs of cerebellar degeneration. There
      was no pigmentary retinal dystrophy; only 3 patients had background diabetic
      retinopathy, despite a median duration of diabetes of 24 years.
      Electroretinography was normal in 3 patients and showed reduced amplitude in 3
      patients; visual evoked responses were abnormal (10/10 patients: reduced
      amplitude to both flash and pattern stimulation). Magnetic resonance imaging
      showed generalised brain atrophy with reduced signal from the optic nerves and
      chiasm. A postmortem brain specimen from one patient revealed atrophy of the
      optic nerves, chiasm, cerebellum and brainstem. We found no evidence of
      mitochondrial genome defects or rearrangements. This primary neurogenerative
      disorder presents with diabetes mellitus and progressive optic atrophy, probably
      due to pathology in the optic nerve.

PMID- 9537153
TI  - Paraneoplastic retinopathy associated with metastatic cutaneous melanoma of
      unknown primary site.
AB  - PURPOSE: To describe further the clinical and immunological features of cutaneous
      melanoma-associated retinopathy, which is an infrequent form of paraneoplastic
      syndrome. METHODS: We studied the salient clinical and immunological aspects of a
      66-year-old man with metastatic cutaneous melanoma to lymph nodes of unknown
      primary site who developed melanoma-associated retinopathy. RESULTS: There was
      gradual loss of vision in the left eye. Colour vision and night vision were not
      affected. Visual fields showed arcuate defects. A full-field electroretinogram
      demonstrated attenuation of the b-wave amplitude in the left eye. The a-wave was
      intact. Indirect immunofluorescence techniques showed that the antibody reactions
      took place mainly in the outer plexiform layer of the retina. CONCLUSIONS:
      Bipolar cells seem to be the target in melanoma-associated retinopathy. Contrary
      to previous reports, night blindness may not be a universal finding.

PMID- 9537154
TI  - The validity of current clinical tests of contrast sensitivity and their ability
      to predict reading speed in low vision.
AB  - PURPOSE: Contrast sensitivity (CS) testing using chart tests of CS is becoming
      increasingly common in low vision assessment. Yet we know little about the
      validity of these charts, i.e. which region of the spatial frequency spectrum is
      being measured. In this study we aimed to determine the validity of currently
      available CS charts by comparison against oscilloscope-based CS. We also
      determined their relative ability to predict reading speed. METHODS: CS was
      measured with five commercially available charts and the contrast sensitivity
      function was determined with sinusoidal gratings presented on a Joyce screen
      using a two-alternative forced choice staircase technique in 36 observers with
      low vision and 3 with normal vision. Reading rate was also measured with the
      subject reading with his or her own optical low vision aid. RESULTS: The results
      show that the Pelli-Robson chart and the Cambridge gratings are good measures of
      medium to low spatial frequencies, as would be predicted from their design, while
      the Regan and UW charts correlated with medium to high frequencies. The Vistech
      chart was a good predictor of CS at each spatial frequency. CONCLUSIONS: The best
      chart test of CS depends on which region of the CS curve is of interest. All the
      charts were good predictors of reading rate.

PMID- 9537155
TI  - Glaucoma.

PMID- 9537156
TI  - Amacrine cells of the mammalian retina: neurocircuitry and functional roles.
AB  - Since amacrine cells are important interneurons of the inner retina and their
      activity may be detected in certain waveforms of the electroretinogram, this
      paper reviews their morphologies, classification, mosaics, neurotransmitter
      content, neural circuitry and physiological responses to light. Nine different
      amacrine cell types of cat, rabbit and human retinas are presently quite well
      studied in terms of the aforementioned aspects and are described in detail in
      this paper.

PMID- 9537157
TI  - The pattern electroretinogram in anterior visual pathway dysfunction and its
      relationship to the pattern visual evoked potential: a personal clinical review
      of 743 eyes.
AB  - The pattern electroretinogram (PERG) has now been in routine clinical use for
      sufficiently long to allow a personal clinical review of its relationship to the
      cortically generated pattern visual evoked potential (PVEP). The PERG and PVEP
      findings are presented from 520 eyes with optic nerve demyelination (382 eyes),
      optic nerve compression (90 eyes) or heredofamilial optic atrophy (48 eyes), and
      these are compared with the findings obtained in 223 eyes with dysfunction
      anterior to the retinal ganglion cells. Dysfunction anterior to the retinal
      ganglion cells gives a reduction in the P50 component of the PERG, but this
      component is usually spared in optic nerve disease where selective loss of the
      N95 component is by far the most frequently occurring abnormality. A diagnostic
      strategy is presented.

PMID- 9537158
TI  - Malignant melanoma of the lacrimal sac.

PMID- 9537159
TI  - Acanthamoeba as a 'transient' in the corneal scrape of a poorly compliant soft
      contact lens wearer with peripheral keratitis.

PMID- 9537160
TI  - Metastatic adenocarcinoma presenting as an isolated ciliary body tumour.

PMID- 9537161
TI  - Lipaemia retinalis in a premature infant with type I hyperlipoproteinaemia.

PMID- 9537162
TI  - An unusual case of acute idiopathic blind spot enlargement syndrome.

PMID- 9537163
TI  - Leakage of Mercury from a McIntyre Bag.

PMID- 9537164
TI  - Consecutive keratitis and Candida endophthalmitis in an immunocompromised patient
      with chronic lymphocytic leukaemia.

PMID- 9537165
TI  - A comparative study of the efficacy of 2.5% phenylephrine and 10% phenylephrine
      in pre-operative mydriasis for routine cataract surgery.

PMID- 9537166
TI  - Astigmatism decay immediately following suture removal.

PMID- 9537167
TI  - CS gas injury.

PMID- 9537168
TI  - Amblyopia.

PMID- 9537169
TI  - [Peripharyngeal space. Pathology].
AB  - Tumors are the most frequent pathological pattern found in the peripharyngeal
      space. Topographically, intrinsic and extrinsic tumors can be distinguished.
      Intrinsic tumors are mostly salivary, nervous and vascular. Extrinsic tumors
      extend from the oral cavity, pharynx and parotid gland. MRI globally gives more
      impressive results than CT. Diagnosis of the tumor type often remains dubious in
      intrinsic tumors. CT-guided biopsy is then required.

PMID- 9537170
TI  - [Helical x-ray computed tomography of renal arteries. Apropos of 300 patients].
AB  - PURPOSE: To evaluate the role of helical CT angiography (CTA) in the detection of
      renal artery stenosis in hypertensive patients. MATERIALS AND METHODS: We studied
      300 hypertensive patients (50 prospectively and 250 consecutively) with CTA and
      arteriography (n = 118). Helical acquisition (collimation 3 mm; pitch = 1, 20
      seconds acquisition time) was performed 20-45 seconds after contrast injection
      (300 mgl/ml; 120 ml, 4 ml/sec). Transverse axial views and 3D reconstructions
      were analyzed (360 degrees interpolation algorithm, 1 mm overlapped). RESULTS: In
      the prospective series, CTA sensitivity was 100% for main renal artery stenoses
      and specificity was 98.2%; however 7/32 renal accessory arteries were not
      visualized. In the 300 patients studied, seventy-four stenoses were detected.
      There were 5 false-positive and 5 false-negative studies. Secondary hypertension
      was detected in 26% of patients (including 14 cases of adrenal hyperplasia).
      CONCLUSION: CTA is a promising technique for the detection of renal artery
      stenosis in hypertensive patients.

PMID- 9537171
TI  - [Angioplasty of renal artery stenoses before surgical treatment of subrenal
      abdominal aortic lesions].
AB  - PURPOSE: To evaluate the results of the association of a percutaneous
      transluminal renal angioplasty before a surgical revascularization of the infra
      renal aorta. PATIENTS AND METHODS: Percutaneous transluminal angioplasty of one
      (n = 12) or two (n = 2) renal arteries have been performed in 14 patients (11
      hypertensive and one with azotemia), 2 to 240 days (mean 54) before infra-renal
      aortic surgery (aneurysms: 8, occlusive disease: 6). RESULTS: 15 of the 16
      dilatations were completely technically successful (residual stenosis less than
      20%), with one groin hematoma treated medically. Mean duration of the surgical
      intervention were 137 minutes (occlusive disease) and 147 minutes (aneurysm). In
      the post-operative course were noted resolutive infections in two patients, and
      one death because of myocardial infarction. At the end of the follow-up (3 to 60
      months, mean 32), all of the 13 patients alive had improved in terms of vascular
      disease. Hypertension was improved for 2 patients, stable for 10, worse for 1.
      Creatinine serum level was stable for 12 patients, and the renal insufficient was
      worsened. CONCLUSION: Combined percutaneous transluminal renal angioplasty and
      aortic revascularization seems to be reliable and safe; it can be an alternative
      to a simultaneous aortic and renal revascularization, notably for high-risk
      patients.

PMID- 9537172
TI  - [Diaphragm kinetics coupled with spirometry. M-mode ultrasonographic and
      fluoroscopic study; preliminary results].
AB  - Most techniques used so far for the evaluation of diaphragm kinetics are either
      invasive (electromyography, fluoroscopy), or indirect (respiratory pressures,
      impedance plethysmography). The aim of this study was to determine whether
      assessment with ultrasound or fluoroscopy differed, and which technique appeared
      more suitable in the investigation of quantitative hemidiaphragmatic
      displacement. Six patients (3 female, 3 male, aged 29 to 40) without respiratory
      disease were studied during systematic X-Ray chest examination, spirometry, and
      abdominal sonography. The amplitude of the right diaphragm motion could be
      measured in all patients with M-mode sonography as well as with fluoroscopy. The
      vertical ascending motion of the diaphragm measured by M-mode sonography, reached
      60% of its maximum amplitude at 50% of inspiratory capacity. There was a
      significant correlation between the maximum amplitude of diaphragm motion as
      measured by M-mode sonography (5.8 +/- 0.4 cm; r = 0.89; p = 0.019) or
      fluoroscopy (5.6 +/- 0.7 cm; r = 0.84; p = 0.036) and the inspiratory capacity
      (2.73 +/- 0.39 l). M-mode sonography has technical, quantitative and qualitative
      advantages over fluoroscopy and should be the method of choice in the
      investigation of suspected diaphragmatic movement disorder. When coupled with
      other techniques like spirometry, this technique could represent a useful adjunct
      to functional respiratory studies.

PMID- 9537173
TI  - [Ultrasonography of amebic liver abscesses. Proposal of a new classification].
AB  - The different classifications used for amebic liver abscesses seem to be usually
      without direct therapeutic benefit. Echographic assessment was used to propose a
      new classification of amebic liver abscesses. This report is a prospective study
      conducted over 3 years and concerning 118 patients involved by 119 amebic liver
      abscesses. They were 109 males and 9 females aged from 13 to 68 years (mean, 36
      years). All cases were correctly diagnosed by clinical and ultrasound findings,
      aspect of the pus, course under treatment and rarely by serologic examinations (3
      patients). Patients were followed up with clinical and sonographic examinations
      as requested. Our classification was based on the initial echographic examination
      findings, the therapeutic indications and the type of healing obtained. In total,
      93 abscesses (80, 67%) were treated by medical therapy alone and 26 cases (21,
      84%) by combined US-guided evacuation and medical therapy. In the 119 abscesses,
      112 (94, 11%) completely recovered with reconstitution of a normal liver
      parenchyma. In the remaining 7 cases (5, 88%) the abscesses persisted for several
      months (12 to 36 months). Our study suggests that ultrasonographic features of
      amebic liver abscesses can be segregated in three forms: noncollected form which
      needs to be treated by medical therapy alone, collected form which can be treated
      medically or by association with US-guided evacuation, and the healing forms.
      This classification appears to us to be simple but very precise, reliable and
      useful especially for therapeutic indications of amebic liver abscesses.

PMID- 9537174
TI  - [Primary intraosseous meningioma of the vault].
AB  - Primitive intra-osseous meningioma is a rare benign tumor. We report a case with
      a temporal localization and antro-attical extension into the petrous bone.

PMID- 9537175
TI  - [Metastatic epiduritis with invasiveness of the left renal vein].
AB  - We report a case of epidural metastasis with left renal vein invasion. This
      nonsymptomatic venous involvement was detected by ultrasonography and confirmed
      at CT and MR imaging. Such an unusual cause of renal vein tumor thrombus occurred
      through a lumbar vein which represents one of its usual collateral branches.

PMID- 9537176
TI  - [Uncommon etiology of multiple pulmonary nodules. Cryptogenic organizing
      pneumonia].

PMID- 9537177
TI  - [Imaging of a case of wirsungorrhagia].
AB  - We report a case of wirsungorrhagia related to rupture of a pseudoaneurysm into
      the duct of Wirsung in a patient with chronic pancreatitis. Upper
      gastrointestinal endoscopy showed blood coming from the papilla of Vater
      suggesting wirsungorrhagia. Non-contrast computed tomography showed a spontaneous
      hyperdensity and arteriography showed an extravasation of contrast within a very
      large duct of Wirsung confirming wirsungorrhagia. Arteriography and dynamic
      computed tomography revealed a pseudoaneurysm from the left gastric artery. The
      pseudoaneurysm was successfully embolized with four steel microcoils, after super
      selective catheterization of small branch of the left gastric artery, keeping
      gastric and liver vascularization.

PMID- 9537178
TI  - [Sinus pericranii].

PMID- 9537179
TI  - [MRI cholangiopancreatography in the pathology of the bile ducts and pancreas].
AB  - MR cholangiopancreatography (MRCP) is a recent and exciting imaging modality that
      allows visualization of bile and pancreatic ducts without morbidity. Although the
      technique of MRCP is in its early stages of development and MRCP technology is
      progressing MRCP will undoubtedly replace traditional techniques such as
      diagnostic ERCP. This article describes MRCP findings in bile or pancreatic duct
      diseases, analyzes the accuracy of MRCP in these diseases, and discusses the
      potential role of MRCP in evaluating the pathology of the biliary tract and
      pancreas.

PMID- 9537181
TI  - [Chronic external instability of the ankle. Contribution of dynamic
      radiographies, x-ray computed tomography and x-ray computed tomographic
      arthrography].
AB  - We retrospectively evaluated the anterior talo fibular ligament and the tarsal
      sinus of 17 patients who had complained of chronic ankle external instability.
      This study based on both surgery and CT-arthrography findings shows the
      pathologic or normal aspects of the talo-fibular anterior ligament (normal, lax,
      fibrosis residue, ruptured). It confirms the good anatomic analysis of the tarsal
      sinus, in particular the anterior talo-calcaneal interosseous ligament and the
      search for fibrosis. We underline that capsular distension due to subtalar laxity
      is not detected with medical imaging. Compared with surgery (all patients), CT
      arthrography demonstrated the different aspects of the anterior talo fibular
      ligament injuries (normal, lax, discontinuous).

PMID- 9537180
TI  - [Techniques of MRI cholangiopancreatography. History, current status and future
      prospects].
AB  - Magnetic resonance cholangiopancreatography (MRCP) is a recent, non invasive,
      diagnostic modality capable of producing high quality images of biliary and
      pancreatic ducts. On the basis of the literature and our experience, we report
      the history and the current status of this new technology, including 2D, 3D and
      single shot fast spin echo sequences. As perspectives echo-planar imaging and
      functional imaging are discussed.

PMID- 9537182
TI  - [MRI in the diagnosis of osteoid osteoma].
AB  - INTRODUCTION: Osteoid osteoma (OO) is a frequently encountered benign bone tumor,
      seen in young adults with male predominance. MATERIALS AND METHODS: Nine patients
      complaining of nonspecific extremity pain underwent MRI examination. The
      sequences obtained were T1 and T2 weighted spin-echo and T2 weighted gradient
      echo. A CT scan examination followed in all cases, exploring the region of the
      abnormal signal seen on MRI. The results of both examinations were compared.
      RESULTS: In six of the nine patients (66.6%) MRI showed evidence suggestive of
      osteoid osteoma, comparable that seen on CT scan. In three patients (33.3%), MRI
      showed a nonspecific and ill-defined bone marrow signal abnormality. CT cuts
      focused on those areas of signal abnormality showed the nidus. DISCUSSION: MRI is
      more sensitive than CT scan in detecting soft tissue and bone marrow
      abnormalities adjacent to an osteoid osteoma. This may produce a misleading
      aggressive appearance on MR images. CT scanning is more specific than MRI, by
      showing the nidus. In three patients studied, the nidus was only seen by CT, the
      other six osteoid osteomas were equally seen by CT and by MRI. In our study, MRI
      revealed abnormalities in all the cases. It was also highly specific for osteoid
      osteoma in 66.6%. CONCLUSION: MRI is very sensitive in detecting bone marrow and
      soft tissue abnormalities, and can suggest the diagnosis of OO in a good number
      of patients. In the remainder cases MRI guides the CT-scan. CT is more accurate
      and remains the definite examination for the diagnosis of OO, by showing the
      nidus.

PMID- 9537183
TI  - [Detection of renal artery stenoses by MRI with surface reconstruction. Value in
      patients with chronic renal failure].
AB  - Forty-three patients with renal artery stenoses were examined with time of flight
      MR angiography using maximum intensity projection and surface shaded rendering,
      and with digital substraction angiography. Sensitivity and specificity were 0.83
      and 0.78 for main and secondary arteries, 0.87 and 0.84 for main arteries. In
      azotemic patients, the positive predictive value was estimated at 40%-70% and the
      negative predictive value at 95%-98%, while the prevalence of renal artery
      stenoses varied from 10% to 30%. These results validate MRI for the detection of
      renal artery stenoses in this population. Surface shaded display was more
      accurate than maximum intensity projection to reconstruct time of flight
      sequences and to grade renal artery stenoses.

PMID- 9537184
TI  - [Influence of naso-sinusal anatomic variants on recurrent, persistent or chronic
      sinusitis. X-ray computed tomographic evaluation in 112 patients].
AB  - Using CT scan, we studied the influence of the most important sinonasal anatomic
      variants on 112 patients, aged more than 16 years, suffering from recurrent,
      persistent or chronic sinusitis. The series was characterized by the absence of:
      multifocal sinusitis, polyposis, dental or mycotic sinusitis, traumatic, tumour,
      actinic or prior surgery. We compared our results with those of the literature.
      Our findings confirmed the association between recurrent, persistent or chronic
      sinusitis, and ipsilateral septal ridges or spurs (33%), unusual ipsilateral
      deflexions of uncinate process (31%), and contralateral septal watch glass like
      deviation (42%). We found no correlation for the other studied variants (concha
      bullosa, paradoxical curve of middle turbinate, pneumatised uncinate process,
      hypertrophic ethmoid bulla, Haller cell and accessory maxillary ostium).

PMID- 9537185
TI  - [Disseminated tuberculosis of unusual locations].
AB  - We report a case of disseminated tuberculosis involving the middle ear, the
      central nervous system, the spine and the lung. The tuberculous epidural abscess
      and otomastoiditis don't have any specific imaging features. But their
      coexistence with an other tuberculous involvement might suggest their tuberculous
      nature. The epidural abscess may result from direct extension from
      otomastoiditis.

PMID- 9537186
TI  - [Cavo-mesenterico-portal shunt in inferior vena cava obstruction].
AB  - We report a case of cavo-mesenterico-portal shunt in vena cava obstruction. The
      main role and frequency of this preferential pathway are reviewed and analyzed.

PMID- 9537187
TI  - [Gorham disease with prominent pleuropulmonary manifestation].
AB  - Gorham's disease usually manifests as diffuse osteolysis but may be complicated
      with pleural effusion. We describe the case of a 12 year-old boy who had repeated
      pleural effusions. Radiographs show a mediastinal widening and an interstitial
      syndrome related to hemolymphangiomatous involvement.

PMID- 9537188
TI  - [Mediastinal neuroectodermal tumor. Apropos of a case].
AB  - Peripheral malignant neuroectodermal tumors are rare and aggressive small-cell
      tumors seen predominantly in children and young adults. Mediastinal location is
      very uncommon. A mediastinal primitive neuroectodermal tumor was diagnosed in a
      27-year-old man. Despite treatment combining surgery, radiotherapy and
      chemotherapy, disease recurred locally along with lungs, spinal and epidural
      metastases, leading to death. CT and MRI examinations show heterogeneous masses
      with necrosis, hemorrhage and intense enhancement after Gadolinium injection. The
      CT and MRI findings are not specific and the diagnosis is based on pathologic,
      immunohistochemical and electron microscopic features. Although uncommon,
      peripheral neuroectodermal tumor should be considered in the differential
      diagnosis of posterior mediastinal masses in children and young adults.

PMID- 9537189
TI  - [Neonatal cystic neuroblastoma].

PMID- 9537190
TI  - [Arteriography of the hand. Technical aspects].
AB  - Arteriography of the hand has specific indications. Digital subtraction
      angiography, use of pneumatic garrot to inject Buflomedyl and to create a post
      ischemic hyperhemia, can give an excellent arterial and venous opacification of
      the hand without general anesthesia. The different stages of the arteriography
      are examined and argued.

PMID- 9537191
TI  - Axillary node dissection in ductal carcinoma in situ.
AB  - Intraductal carcinoma of the breast has become a well-defined entity that has
      been more frequently diagnosed since the introduction of mammography. For many
      years, the usual treatment has been mastectomy, often with axillary lymph node
      dissection. Concurrent with documentation that breast conservation treatment has
      been effective for many invasive breast cancers, such treatment has been
      introduced for noninvasive breast cancers (ductal carcinoma in situ and lobular
      cancer in situ). However, there is no basis for axillary dissection because tumor
      cells are contained by the basement membrane and should not metastasize. In this
      study, 107 axillary dissections were carried out, with an average of 20 nodes
      identified, and a single metastasis was identified.

PMID- 9537192
TI  - Prognostic factors after conservative surgery and radiation therapy for early
      stage breast cancer.
AB  - A retrospective review was conducted of all early-stage breast cancer patients
      treated with breast-conservation surgery plus radiation therapy (BCS/RT) to
      determine mortality and recurrence rates and to evaluate prognostic factors for
      these outcomes. Between 1982 and 1988, 121 patients with stages I and II breast
      cancer were treated with BCS/RT at our institution. Most of the patients (83%)
      had re-excision of the initial biopsy site and at final surgical evaluation, only
      4 patients had positive margins (3.2%). Median follow-up was 89.7 months. Cox
      proportional hazards regression models were used to select prognostic factors
      significant for breast cancer-specific mortality, overall disease recurrence, and
      local recurrence. Breast cancer survival rates were 92% at 5 years and 83% at 10
      years. Prognostic factors predicting breast cancer mortality included positive
      lymph nodes (relative risk=.9; 95% confidence interval, 1.2,12.2) and a higher
      grade (relative risk=1.9; 95% confidence interval, 1.1,3.3). For disease
      recurrence, prognostic factors included positive nodes (relative risk=2.6; 95%
      confidence interval, 1.2, 5.5), and a negative progesterone-receptor status
      (relative risk=0.3; 95% confidence interval, 0.2, 0.8). Local recurrence rates
      were 2.5% at 5 years and 14% at 10 years. No prognostic factors were significant
      for local recurrence; however, most patients had negative margins after surgery.

PMID- 9537193
TI  - Primary chemotherapy in breast cancer: correlation between tumor response and
      patient outcome.
AB  - This study focused on the correlation between tumor response and patient outcome
      in 329 breast cancers treated with primary chemotherapy. There were 141 stage
      IIIB tumors, including 109 inflammatory carcinomas. Other malignancies (34 IIIA,
      99 IIB, 55 IIA) were operable but considered to be too large (> 3 cm) for
      conservative surgery and received primary chemotherapy to avoid mastectomy. All
      received the AVCF regimen, comprising 4-week cycles of doxorubicin (30 mg/m2) day
      1, vincristine (1 mg/m2) day 1, 5-fluorouracil (5-FU; 400 mg/m2) days 2 through
      5, cyclophosphamide (300 mg/m2) days 2 through 5. In 189 cases, methotrexate (15
      mg/m2) was added at day 2 and day 3. Patients received 6 cycles, then underwent
      locoregional treatment (surgery, radiotherapy, or both) according to tumor
      regression. The response rate was assessed by clinical, mammographic, and
      echographic examinations: a 50% rate of objective responses were noted, of which
      15% were complete responses (tumor shrinkage allowed breast conservation in 68%
      of patients who had stages II or IIIA). For the whole population studied, median
      follow-up was 111 months (range, 60- 196). One hundred fifty-seven patients had
      disease relapse (48 local, 14 contralateral, 95 distant). Kaplan-Meier estimates
      showed an increased 10-year overall survival for patients in complete response,
      as compared with noncomplete response: 70% versus 50% (p < 0.03). Complete
      response to neoadjuvant chemotherapy seems a good prognostic factor.

PMID- 9537194
TI  - The management of metastatic squamous cell carcinoma in cervical lymph nodes from
      an unknown primary.
AB  - A patient is diagnosed with an unknown primary of the head and neck when
      metastatic disease is present in the cervical lymph node or nodes and no primary
      lesion is detected by thorough physical examination, directed biopsies of
      suspicious or most likely primary sites, and imaging studies. The optimal
      management of patients who have this syndrome is still unclear and controversial.
      We report our results and analysis of the management of 24 patients with this
      syndrome. From 1976 through 1992, 24 patients who had metastatic squamous cell
      carcinoma in the cervical lymph nodes were seen in our medical center. A thorough
      search did not detect a primary lesion in any of them. Patients underwent radical
      neck dissection of the involved neck; 23 had unilateral and I had bilateral neck
      disease. Postoperative radiotherapy was delivered to both sides of the neck and
      to the potential primary mucosal and submucosal sites. The relation between
      clinical N stage, histologic findings of numerous involved lymph nodes, presence
      of extracapsular tumor extension, and survival were statistically analyzed. The
      Kaplan-Meier method was used for the survival analysis. The p values of log-rank
      test for the comparison of the two groups 1) N1 and N2 versus N3, and 2) presence
      of extracapsular tumor extension versus its absence are less than 0.005, with
      extracapsular tumor extension versus nonextracapsular tumor extension slightly
      smaller. The 5- and 10-year disease-free survival rate for the entire group was
      54.2% (70.5% for N1 and N2, and 14.2% for N3). Three patients had locoregional
      failure, two in the primary sites, one in the nasopharynx, and the other in the
      oropharynx (the latter also had recurrent disease in the undissected neck). In 8
      patients, distant metastases developed 7 to 38 months after radiotherapy. All 11
      patients (45.8%) who had recurrent disease had advanced clinical N stage,
      microscopic findings of numerous involved lymph nodes, and prominent
      extracapsular tumor extension to the surrounding soft tissue and blood vessels.
      The high incidence of distant metastases shortly after treatment suggests a
      hematogenous spread before treatment in patients who had extensive nodal and
      extranodal disease. Our long-term disease-free survival beyond ten years seems to
      indicate combined treatment modalities, including radical neck dissection with
      postoperative radiotherapy of the neck, and the potential primary site in
      patients with N2 and N3 disease (our N1 group is too small for analysis). Further
      improvement of cure rate can be expected in the future with early detection and
      treatment.

PMID- 9537195
TI  - Detection of unsuspected recurrent lymphoma with fluorodeoxyglucose-positron
      emission tomographic imaging after induction chemotherapy: a case study.
AB  - We performed a fluorodeoxyglucose-positron emission tomographic (FDG-PET) study
      on a patient who had high-grade lymphoma thought to be in complete remission. The
      patient underwent the PET study before being considered for high-dose
      consolidation therapy because he was thought to be at high risk for relapse. The
      whole-body FDG-PET study revealed an unsuspected hypermetabolic mass in the lower
      spine that was not visualized on computed tomographic (CT) scanning. The other
      laboratory values were normal, with the exception of mild lactate dehydrogenase
      elevation. Two weeks later, the patient developed low back pain, and magnetic
      resonance imaging showed a 2-cm paraspinal mass at the level of L4. Bone-marrow
      biopsy confirmed recurrent lymphoma. Remission was not achieved after another
      chemotherapy regimen. Fluorodeoxyglucose-positron emission tomography can be
      helpful in the restaging of lymphoma patients after induction chemotherapy and
      may help to detect early recurrence in selected situations.

PMID- 9537196
TI  - Phase I study of paclitaxel and etoposide for metastatic or recurrent
      malignancies.
AB  - The authors define the dose-limiting toxicities and the recommended phase II
      doses of paclitaxel combined with etoposide, without and with filgrastim support.
      Patients with advanced solid tumors were eligible if they had a performance
      status of 0 to 2 and normal renal, hepatic, and bone marrow function. Patients
      with cardiac arrhythmias or congestive heart failure requiring medical therapy
      were excluded. Prior radiation was allowed only if it involved less than 30% of
      the marrow-containing skeleton. The dose of etoposide was fixed at 100 mg/m2/d
      for 3 days beginning on day 1. Paclitaxel was administered over 3 hours on day 4.
      The dose of paclitaxel was escalated until the maximum tolerated dose (MTD),
      without and with filgrastim 5 microg/kg (or 300 microg total dose) subcutaneously
      beginning on day 5, was reached. Treatment cycles were repeated every 21 days. Of
      39 patients entered, 37 were evaluable for toxicity and 30 for response. The
      principal toxicity was neutropenia. Without filgrastim, the MTD of paclitaxel was
      150 mg/m2. With filgrastim, the dose of paclitaxel was escalated to 250 mg/m2 in
      combination with etoposide 100 mg/m2. One episode of pulmonary toxicity was
      observed. Five patients responded: two with previously treated non-small-cell
      lung cancer (NSCLC), two with refractory small-cell lung cancer (SCLC), and one
      with refractory germ-cell tumor (GCT). We conclude that paclitaxel and etoposide
      can be given in combination at clinically relevant doses with filgrastim support.
      In this phase I trial, a dose of paclitaxel of 200 mg/m2 on day 4 and etoposide
      at 100 mg/m2/d on days 1-3, with filgrastim 5 microg/kg beginning on day 5, was
      found to be well tolerated, and can be recommended for future studies. Without
      filgrastim, a paclitaxel dose of 150 mg/m2 with the same dose of etoposide can
      also be recommended.

PMID- 9537197
TI  - Octreotide does not prevent diarrhea in patients treated with weekly 5
      fluorouracil plus high-dose leucovorin.
AB  - The somatostatin analog, octreotide, is effective in treating diarrhea associated
      with cancer chemotherapy. This study was undertaken to determine whether
      octreotide could be used as prophylaxis against chemotherapy-induced diarrhea
      and, thereby, permit increased dose intensity. Adult cancer patients were treated
      with a standard regimen of intravenous 5-fluorouracil (5-FU) (600 mg/m2) plus
      leucovorin (LV) (500 mg/m2) weekly x 6 weeks. In addition, 150 microg of
      octreotide was administered subcutaneously twice daily, beginning on the first
      day of chemotherapy and continuing for 43 days. Escalation of 5-FU was planned
      for successive cohorts based upon toxicity. Eleven patients were treated at the
      initial 5-FU dose level. In 10 evaluable patients, dose-limiting toxicities were
      diarrhea (two patients), fatigue (one patient), and hyperbilirubinemia (one
      patient). Diarrhea was experienced by six of 10 patients, and only three patients
      were able to receive six weekly chemotherapy treatments without dose reduction or
      delay. At a dose of 150 microg twice daily, octreotide did not prevent diarrhea
      associated with 5-FU plus LV, and 5-FU dose escalation was not possible. While
      octreotide is successful in the treatment of 5-FU-induced diarrhea, we were
      unable to demonstrate a role in toxicity prophylaxis.

PMID- 9537198
TI  - Combined levamisole with recombinant interleukin-2 (IL-2) in patients with
      advanced renal cell carcinoma: a phase II study.
AB  - Adoptive immunotherapy (AI) with interleukin-2 (IL-2) and lymphokine-activated
      killer (LAK) cells is an antineoplastic modality in which immune-activated cells
      are administered to a host having cancer in an attempt to mediate tumor
      regression. Levamisole (LEV), an immune stimulant, has been suggested as having
      therapeutic effectiveness in a variety of cancers. After a phase I trial of
      recombinant IL-2 plus LEV, a phase II trial of this combination was conducted in
      patients who had advanced renal cell carcinoma. The regimen was IL-2 at 3 x 10(6)
      U/m2 daily x 5 plus LEV at 50 mg/m2 perorally three times a day x 5. Only one of
      the 22 eligible patients had a regression. It was a partial regression, 85 days
      in duration. The median time to treatment failure (refusal, progression, or off
      study because of toxicity) was 36 days. The only grade 4 toxicity reported was
      lethargy. This regimen is not recommended for further testing in patients who
      have advanced renal cell carcinoma.

PMID- 9537199
TI  - Treatment of acute myelogenous leukemia in the older patient with attenuated high
      dose ara-C.
AB  - We have evaluated the activity and toxicity of cytosine arabinoside (ara-C; 750
      mg/m2 intravenously given over 3 hours every 12 hours for 12 doses) to induce
      remission in older (median age, 73 years) newly diagnosed patients who had acute
      myelogenous leukemia (AML). A maximum of two cycles of induction were
      administered. Patients who achieved complete remission could receive three
      additional consolidation courses limited to 4 to 6 doses of ara-C every 12 hours,
      depending on marrow cellularity. Thirty patients were evaluable. Twenty-two
      patients had one or more unfavorable prognostic factors, including antecedent
      hematologic disorders (10), cytogenetic abnormalities (17), or hyperleucocytosis
      (5). Fourteen patients (47%) achieved complete remission. Four patients did not
      receive consolidation as planned because of medical contraindication or refusal,
      and three patients relapsed during consolidation. The median duration of complete
      remission was 326 days. Sixteen patients failed induction because of relative or
      absolute drug resistance in nine patients, or death in seven patients. Median
      survival for the entire group was 6 months. Toxicity was significant, with a
      median initial hospitalization of 29 days. These results are comparable to those
      reported in the literature and suggest that this regimen may be considered to be
      an alternative to an anthracycline-containing regimen.

PMID- 9537200
TI  - Amonafide in patients with leiomyosarcoma of the uterus: a phase II Gynecologic
      Oncology Group study.
AB  - Twenty-six evaluable patients who had leiomyosarcoma of the uterus were treated
      with amonafide, 300 mg/m2, for 5 consecutive days every 3 weeks. One partial
      response (4%) resulted. Hematologic toxicity was substantial, with grade 3 or 4
      events occurring as follows: leukopenia, 12 patients (46%); thrombocytopenia, 4
      patients (15%); and granulocytopenia, 7 patients (27%). One patient had transient
      grade 4 renal failure. Considering the poor activity and substantial toxicity
      that was observed, no further studies are planned by the Gynecologic Oncology
      Group using amonafide at this dose schedule in leiomyosarcomas.

PMID- 9537201
TI  - Continuous venous infusion 5-fluorouracil and interferon-alpha in pancreatic
      carcinoma.
AB  - Chemotherapy treatment for advanced pancreatic cancer is universally
      disappointing. Evidence suggested the possibility of improved activity of 5
      fluorouracil (5-FU) in this disease when administered by continuous infusion in
      combination with interferon-alpha. Thirteen patients who had histologically
      documented stage III and IV adenocarcinoma of the pancreas were treated with 5
      FU, 250 mg/m2/day by continuous infusion, in combination with interferon-alpha, 3
      million units subcutaneously 3 times per week. Treatment was adjusted for
      toxicity and was continued until disease progression, unacceptable toxicity, or 8
      weeks after a complete response. Responses were documented on two separate
      occasions that were separated by 4 weeks. Eleven men and two women were treated
      an average of 48 days. There was one responder, for a response rate of 7.7% (95%
      confidence interval, 0.1%-36%). The duration of response was 90 days. The median
      survival of the entire group was 8.3 months. Toxicity was significant, with more
      than 50% of patients requiring treatment breaks and dosage reductions. The most
      common toxicities were mucositis, hand-foot syndrome, diarrhea, and nausea. There
      were no treatment-related deaths. Treatment of advanced adenocarcinoma of the
      pancreas with continuous-infusion 5-FU and interferon-alpha is associated with
      significant toxicity without significant evidence of response.

PMID- 9537202
TI  - Seventy-two hour epirubicin infusion plus quinidine in unresectable and
      metastatic adenocarcinoma of the pancreas: a phase II trial.
AB  - Twenty-two previously untreated patients who had unresectable and metastatic
      pancreatic cancer were treated in a prospective phase II trial with high-dose
      continuous infusion epirubicin (45 mg/m2 once every 24 hours continuous infusion
      days 4 through 6) plus quinidine (495 mg once every 24 hours on days 1-6). There
      were no objective responses (0 of 18 evaluable patients). Subjective responses
      were achieved in 2 of 21 evaluable patients (9%), all of whom had good
      performance status (Eastern Cooperative Oncology Group: 0-1). Median survival was
      5.7 months for the overall population. Two patients who exhibited symptomatic
      improvement achieved responses lasting 7 and 13 months, respectively. Toxicity
      was generally mild and tolerable. Little benefit regarding survival and quality
      of life was observed with the use of this regimen. The role in chemoresistance of
      mdrl, p53, and the mismatch repair system was examined.

PMID- 9537203
TI  - Prognostic value of K-ras mutations, ras oncoprotein, and c-erb B-2 oncoprotein
      expression in adenocarcinoma of the lung.
AB  - This trial was undertaken to determine the prognostic role of K-ras (p21), c-erb
      B-2 (p185) protein expression, and the presence or nonpresence of a K-ras gene
      mutation in patients with adenocarcinoma of the lung. This was a retrospective
      study of 103 patients with adeno- or large-cell carcinoma of the lung who had
      available paraffin-stored tumor material. The relation of several clinical
      variables to survival was analyzed. Immunohistochemical techniques were used to
      determine expression of p21 and p185. Polymerase chain reaction (PCR) and
      sequencing were used to determine K-ras mutation status. Tumor stage was the only
      nonmolecular clinical variable predictive of survival (p=0.0001). A combination
      of K-ras mutation and p 185 expression (p=0.0144), ras mutation and strong p21
      expression (p=0.0137), and K-ras mutation and the combined expression of p21 and
      p185 were predictive of poor survival (p=0.0415) in univariate analysis of all
      patients. The sole presence of K-ras mutation was predictive of survival.
      Additionally, when combined with elevated p21 or p185 expression in a subset of
      patients with 4 or more years of follow-up, negative correlation with survival
      was observed.

PMID- 9537204
TI  - Anastrozole: a new addition to the armamentarium against advanced breast cancer.
AB  - Estrogen manipulation represents an effective treatment for advanced breast
      cancer in postmenopausal women with estrogen-receptor positive disease. The
      antiestrogen agent, tamoxifen, is the first choice for advanced breast cancer in
      postmenopausal women due to its efficacy and lack of significant side effects. As
      with all cancer treatments, however, cancer may recur after initial treatment
      with tamoxifen, and the limitations of currently available alternative hormonal
      therapies in terms of tolerability and convenience of administration underscore
      the need for new agents. Anastrozole is a new, highly selective, nonsteroidal
      aromatase inhibitor capable of maximal estrogen depletion with fewer side effects
      than other hormonal therapies. Anastrozole is administered in a convenient, once
      daily oral dosing regimen and does not require steroid replacement therapy. In
      two multicenter clinical trials, anastrozole was as effective as megestrol
      acetate for the treatment of advanced breast cancer in postmenopausal women who
      progressed after tamoxifen therapy, based on objective response rates and time to
      objective progression of disease. In addition, the drug did not produce the
      weight gain observed with megestrol acetate therapy. Anastrozole is an effective
      endocrine agent in the treatment of advanced breast cancer in postmenopausal
      women.

PMID- 9537205
TI  - Metastatic angiosarcoma of the spleen after accidental radiation exposure: a case
      report.
AB  - Angiosarcoma is a rare malignant tumor arising from endothelial cells of blood
      vessels or lymphatic channels. Therapeutic irradiation, thoriumdioxide
      administration, pyothorax, and polyvinyl chloride exposure have been shown to be
      predisposing factors for developing angiosarcoma. Accidental radiation exposure
      has not been associated with angiosarcoma. We present an unusual case of
      angiosarcoma of the spleen, with metastases to bone, liver, breast, and bone
      marrow, in a woman who lived near the Chernobyl nuclear facility in the former
      Soviet Union at the time of the reactor accident in 1986. To the best of our
      knowledge, this is the first report of metastatic angiosarcoma after accidental
      radiation exposure.

PMID- 9537206
TI  - 5-Fluorouracil and leucovorin therapy in patients with hormone refractory
      prostate cancer: an Eastern Cooperative Oncology Group phase II study (E1889).
AB  - This report is a multi-institutional phase II study designed to obtain the
      response rate, survival, and toxicity profile for patients having hormone
      refractory prostate cancer. Patients who had bidimensionally measurable prostate
      carcinoma in first or second remission after previous hormonal therapy but no
      history of chemotherapy were eligible. Patients were treated with leucovorin, 20
      mg/m2 intravenously, followed by 5-fluorouracil (5-FU), 425 mg/m2 intravenously
      daily for 5 days, with cycles repeated every 28 days. Of 38 eligible patients, 3
      (7.9%) had partial responses to therapy and 20 (52.6%) had stable disease. Median
      survival was 11.6 months for all 38 patients and median time to progression was
      4.4 months. Most of the serious side effects were gastrointestinal or hematologic
      and overall, 23 of 38 patients (60.5%) experienced at least one grade 3 or 4
      treatment-related toxicity of any type, as measured by the National Cancer
      Institute common toxicity criteria. Five patients (13.2%) withdrew from the study
      because of adverse reactions from chemotherapy. We conclude that treatment of
      hormone-refractory prostate cancer patients with 5-FU and leucovorin chemotherapy
      produced few responses at the cost of significant side effects. Further
      investigation of this combination is not warranted in this setting.

PMID- 9537207
TI  - Closure of tracheoesophageal fistulas with chemotherapy and radiotherapy.
AB  - In patients who have esophageal cancer with a tracheoesophageal fistula,
      chemotherapy and radiotherapy are usually contraindicated because it is thought
      to enlarge the fistula. The records of 50 patients who had esophageal cancer and
      received simultaneous chemotherapy and radiotherapy from January 1992 to January
      1997 were evaluated in the Medical Oncology Section of the Veterans
      Administration Medical Center, Washington, D.C. All patients were staged
      radiographically and endoscopically. Four patients developed a tracheoesophageal
      fistula while receiving treatment. One patient developed a fistula before
      treatment and another patient developed a fistula after treatment. Closure of the
      tracheoesophageal fistulas was achieved in 4 of 5 patients who responded to
      therapy and in those who developed fistulas before or during therapy. One of the
      patients whose fistula did not close died during therapy, whereas the other who
      developed a fistula after therapy underwent stenting. This finding indicates that
      development of a tracheoesophageal fistula is not a contraindication to
      chemotherapy and radiotherapy, and patients who are responsive to therapy may
      have closure of their fistulas.

PMID- 9537208
TI  - Paclitaxel plus gallium nitrate and filgrastim in patients with refractory
      malignancies: a phase I trial.
AB  - To determine the maximally tolerated dose of paclitaxel with and without
      filgrastim (G-CSF) when administered as a 24-hour intravenous infusion after a
      120-hour infusion of gallium nitrate at a fixed dose of 300 mg/m2/24 hours, 40
      patients were entered onto a trial lasting from September 1994 to September 1996.
      Eligibility included a diagnosis of an advanced malignancy not amenable to
      curative therapy and up to one previous chemotherapy regimen for metastatic
      disease. Gallium was administered at a fixed dose of 300 mg/m2/day as a
      continuous intravenous infusion for 120 hours. Paclitaxel starting at 90 mg/m2
      was given concurrently with the last 24 hours of the gallium as a 24-hour
      intravenous infusion. Cycles were repeated every 21 days. Once the maximum
      tolerated dose (MTD) of paclitaxel was reached, G-CSF (5 microg/kg/day days 7-16)
      was added and paclitaxel dose escalation continued. The MTD for paclitaxel
      without G-CSF was 110 mg/m2 and 225 mg/m2 with G-CSF, with neutropenia being the
      dose-limiting toxicity. A partial response was noted in a patient who had thymoma
      and a complete response was achieved in a patient who had colon cancer. The
      recommended phase II dosage is gallium nitrate at 300 mg/m2/day over 120 hours,
      with paclitaxel at 110 mg/m2 over 24 hours without G-CSF or 225 mg/m2 over 24
      hours with G-CSF and 0.5 mg calcitriol on days 1 through 7. Further trials of
      this modified regimen for outpatient administration are in progress.

PMID- 9537209
TI  - A comparison of two nonsteroidal antiinflammatory drugs (diflunisal versus
      dipyrone) in the treatment of moderate to severe cancer pain: a randomized
      crossover study.
AB  - The efficacy of diflunisal in cancer pain was evaluated and compared with
      dipyrone. Diflunisal was given at the dosage of 500 mg perorally twice a day, and
      dipyrone was given at the dosage of 500 mg perorally three times a day. Duration
      of each treatment was 7 days; after a 12-hour wash-out period, patients were
      given the other drug for another 7 days. A total of 50 patients were enrolled in
      the study. Pain intensity was assessed by 10-point visual analog scale (VAS).
      Patients who had a VAS score higher than 5 were included. A total of 47 patients
      were evaluable. Initial VAS score was a mean of 8.57+/-1.33. Diflunisal reduced
      the pain score by a mean of 4.65+/-3.10, whereas dipyrone reduced the pain score
      by a mean of 3.25 < or = 2.85 (p < 0.001). Patients were also analyzed in three
      subgroups according to the presence of nonmetastatic, metastatic, and bone
      metastatic diseases. In each of these subgroups, diflunisal reduced the pain
      score more than dipyrone; however, the difference was statistically significant
      only in patients who had bone metastasis. Adverse reactions were rare and
      acceptable with both drugs. Diflusinal is superior to dipyrone at this dosage and
      schedule in the treatment of moderate to severe cancer pain.

PMID- 9537211
TI  - Ifosfamide in the treatment of advanced or recurrent squamous cell carcinoma of
      the head and neck: a phase II Hoosier Oncology Group trial.
AB  - The Hoosier Oncology Group conducted a trial evaluating ifosfamide in patients
      who had recurrent or metastatic squamous cell carcinoma of the head and neck.
      Patients must have received no prior chemotherapy for metastatic disease. If
      prior adjuvant chemotherapy was given, the last cycle must have been at least six
      months from time of recurrence. All patients were required to have a Karnofsky
      performance status of > or = 50. Twenty-four patients received treatment
      consisting of ifosfamide, 1.5 g/m2/day for 5 days, with cycles repeated every 3
      weeks. Mesna, 300 mg/m2, was administered intravenously 15 minutes before
      ifosfamide and 4 and 8 hours after ifosfamide on days 1 through 5. Toxicity was
      predominantly hematologic, with grade 3--4 neutropenia seen in 13 patients
      resulting in 4 episodes of neutropenic fever. One partial response was seen in 23
      evaluable patients for an overall response rate of 4.3% (95% confidence interval,
      0, 12.7%). In conclusion, ifosfamide would appear to have limited single-agent
      activity in squamous cell carcinoma of the head and neck.

PMID- 9537210
TI  - SK&F107647: a synthetic hematoregulatory peptide in patients with solid tumor
      malignancies: a phase I trial.
AB  - SK&F107647 is a synthetic hematoregulatory peptide (HP) increases both the number
      and function of progenitor cells, enabling improved survival after lethal
      myelosuppression, lethal fungal infection, and lethal herpes simplex virus
      infection in murine models. This Phase I single-blind placebo-controlled dose
      rising crossover trial examined the efficacy of SK&F107647 in patients who had
      incurable solid tumor malignancies. Sixteen patients were treated. Six adverse
      events in 3 patients were considered to be possibly related to SK& F107647; all
      were mild to moderate in nature (mild nervousness and agitation at 0.01 ng/kg,
      moderate fever and mild nausea at 0.1 ng/kg, elevated hepatic enzymes at 0.1
      ng/kg, and mild vomiting at 1.0 ng/kg). Plasma half-life was 2.44 hours (+/-1.07
      standard deviation). The observed area volume of distribution was 16.7 L (+/-7.7
      standard deviation) and clearance was 5.04 L/hour (+/-1.83 standard deviation).
      When administered as a single 2-hour intravenous infusion at doses ranging from
      0.01 to 100 ng/kg, SK&F107647 is safe and well tolerated.

PMID- 9537212
TI  - Extragonadal germ-cell tumors: a ten-year experience.
AB  - Extragonadal germ-cell tumors (EGCT) are uncommon and biologically distinct from
      their gonadal counterparts. Thirty-seven patients who had EGCT were treated over
      a ten-year period at the Regional Cancer Centre, Trivandrum, India. There were 26
      men and boys and 11 women and girls. The sites of primary tumor were mediastinum
      (n=18), central nervous system (n=5), sacrococcygeal region (n=4),
      retroperitoneum (n=2), and other sites (n=8). After combined modality therapy, 13
      of 18 patients who had mediastinal EGCT--1 of 2 with retroperitoneal, 1 of 4 with
      sacrococcygeal, 0 of 5 with central nervous system, and 2 of 8 patients with
      tumor in other sites-were alive with no evidence of disease at a median follow-up
      of 16 months. The overall 5-year survival rate was 40%. Histologic subtype and
      elevated marker levels were the significant prognostic factors on univariate
      analysis.

PMID- 9537213
TI  - Preoperative radiotherapy for cancer of the extrahepatic bile duct.
AB  - From January 1988 through June 1996, 12 patients who had extrahepatic bile-duct
      cancer received preoperative radiotherapy at doses of 40.6 Gy to 58.4 Gy. At
      restaging, 1 patient was found to have liver metastases and the remaining 11
      patients were taken to surgery. Nine patients underwent resection, and 8 of the 9
      received intraoperative radiotherapy. Complications occurred in 4 patients, 3 of
      whom died postoperatively. The 2 patients who died of intraabdominal
      complications received both preoperative radiation doses of more than 55 Gy and
      intraoperative radiotherapy doses of 14 Gy or more. Histologic evidence of
      irradiation effects was present in all specimens. Irradiation effects on
      perineural invasion were observed in varying degrees. Two of the four patients
      who had marked irradiation effects on perineural invasion developed local
      recurrence, which was found at autopsy to have infiltrated the hepatic hilum
      without obstructing the hepatic ducts. One patient who had minimal irradiation
      effects on perineural invasion developed local recurrence with obstructing the
      hepatic ducts. Of the 2 patients who had positive margins, the patient with
      marked irradiation effects on perineural invasion survived 18 months, but the
      patient with slight irradiation effects on perineural invasion survived only 5
      months. The high complication rate requires modification of this strategy. The
      propriety of combining preoperative radiotherapy with intraoperative radiotherapy
      as well as the radiation dose should be reinvestigated.

PMID- 9537214
TI  - Interferon alpha-2b and megestrol acetate in the treatment of advanced renal cell
      carcinoma: a phase II study.
AB  - Interferon-alpha has been used to treat advanced renal cell carcinoma, and
      megestrol acetate has been shown to improve the quality of life of patients who
      have cancer. We combined interferon alpha-2b, 10 million IU/m2 subcutaneously 5
      consecutive days per week, with megestrol acetate, 80 mg orally twice a day, in
      15 patients who had advanced renal cell carcinoma. Only 6 (40%) had a prior
      nephrectomy, and most had disease in the lung and other sites. There were no
      complete or partial responders to this treatment, although stable disease was
      achieved in 5 (33%) patients. The treatment was excessively toxic, with 12 (86%)
      patients requiring dose modification or discontinuation of treatment due to
      fatigue. We conclude that interferon alpha-2b and megestrol acetate is an
      excessively toxic, inactive regimen, at least in a group of patients who have
      advanced disease with a poor prognosis.

PMID- 9537215
TI  - Malignant thyroid teratoma of an adult: a long-term survival after chemotherapy.
AB  - Adult primary malignant teratoma of the thyroid is a rare disease that has a poor
      outcome despite aggressive therapy. A 32-year-old woman underwent a simple
      lobectomy of the thyroid for a progressively enlarged nodule in August 1990.
      Pathologic assessment of the tumor revealed a malignant teratoma. The physical
      examinations and image studies failed to find tumor in other sites. She
      subsequently received 6 courses of chemotherapy with cisplatin, etoposide, and
      bleomycin. She experienced a complete response to chemotherapy and remained
      disease-free for 6.5 years. This tumor must be included in the differential
      diagnosis of a thyroid tumor and may be treated as a testicular germ-cell tumor
      for which chemotherapy may be recommended.

PMID- 9537216
TI  - Carboplatin and etoposide for recurrent malignant glioma: one department's
      experience.

PMID- 9537217
TI  - Antiarrhythmic drugs: a reorientation in light of recent developments in the
      control of disorders of rhythm.
AB  - Numerous developments in our knowledge of arrhythmias during the past decade or
      so have had a major influence on antiarrhythmic drug therapy. It has become
      increasingly evident that arrhythmias merit treatment not only for the relief of
      symptoms, with improvement in quality of life, but also for the prolongation of
      survival by decreasing arrhythmic deaths. No longer can mere suppression of
      arrhythmias, symptomatic or asymptomatic, be equated with prolonged survival. We
      now know that antiarrhythmic drugs that act by blocking sodium channels can
      increase mortality and that the most important determinants of arrhythmia
      mortality are the degree and nature of ventricular dysfunction. To these
      considerations must be added the advances in nonpharmacologic approaches to
      controlling cardiac arrhythmias. There has been a shift to the use of implantable
      devices and of drugs with alternative modes of action, such as beta blockers and
      class III drugs (e.g., sotalol, amiodarone). However, the side-effect profiles of
      these 2 classes of compounds have led to the synthesis and characterization of
      agents that act simply by blocking > or = 1 membrane ion channels. The isolated
      block of the rapid component of the delayed rectifier potassium current (IKr) has
      been associated with potent antifibrillatory activity in the atria, with a
      neutral (e.g., with dofetilide) or deleterious (with d-sotalol) effect on
      mortality in postinfarct survivors. Therefore, the focus now is on compounds that
      can block > 1 ion channel (e.g., tedisamil and azimilide). Azimilide is the first
      of the class III agents that blocks both components of the delayed rectifier
      potassium current. The drug's overall action is associated with a spectrum of
      electrophysiologic properties that hold promise in the control of atrial and
      ventricular arrhythmias, with potential for improving survival in patients at
      risk for cardiac arrest.

PMID- 9537218
TI  - Do animal models have clinical value?
AB  - This article examines the efficacy of studying antiarrhythmic and
      antifibrillatory interventions using animal models. The importance of identifying
      appropriate animal models and comparing results from these studies to human
      clinical trials is discussed. Specific studies will be cited, the
      advantages/disadvantages of each design (i.e., internal control analysis factors,
      reproducibility of results, anesthetized vs conscious models) will be presented,
      and their ability or inability to predict clinical outcomes will be discussed.

PMID- 9537219
TI  - Antiarrhythmic drugs: rethinking targets, development strategies, and evaluation
      tools.
AB  - Although antiarrhythmic drugs have the potential to save lives, current
      approaches to drug selection and development preclude exploitation of the full
      potential of such agents. It is therefore important that we reconsider the
      identity and nature of the target sites of such drugs and the strategies used in
      their development. The concept of a vulnerable parameter as a factor contributing
      to arrhythmogenesis, amenable to modulation by drugs or other interventions, has
      helped conceptualize the targeted approach to both drug discovery and drug
      selection. Moreover, broadening our perspectives to include both the triggers of
      and substrates for arrhythmias widens the scope of promising targets for drug
      development programs.

PMID- 9537220
TI  - Can antiarrhythmic drugs survive survival trials?
AB  - Sudden cardiac death due to arrhythmic events is the major cause of mortality
      among early post-myocardial infarction (MI) patients, accounting for > 250,000
      deaths annually in the United States alone. Antiarrhythmic drugs can be used in
      such patients as well as in those who have not had a recent MI but are at high
      risk for sudden cardiac death (e.g., those with ventricular
      tachycardia/fibrillation, or who have survived cardiac arrest). Most
      antiarrhythmic drugs available, however, have limitations arising from their
      toxic and proarrhythmic potential. Thus, research and development of new agents
      and treatment modalities are desirable. This article seeks to enumerate the
      lessons of past clinical trials with these agents and to provide guidelines for
      future trials. That a variety of antiarrhythmic drugs have been associated with
      an increased mortality has been a disturbing observation. It is therefore
      imperative that candidates for antiarrhythmic therapy be selected appropriately.
      We recommend that future clinical trials use stringent criteria for the
      identification of patients at "high risk" for arrhythmia or sudden cardiac death,
      and limit recruitment to such patients. Traditional markers, such as the
      increased frequency and complexity of ventricular premature beats, and low left
      ventricular ejection fraction, have not been successful in identifying these high
      risk patients. However, decreased heart rate variability and cardiac late
      potentials recorded on a signal-over-aged electrocardiogram appear to be more
      specific markers of post-MI arrhythmia or sudden cardiac death and may, in
      conjunction with the traditional markers, be used to improve selection of trial
      populations. Since the risk of sudden cardiac death diminishes with time after
      MI, it is also recommended that the temporal window of treatment with
      antiarrhythmic agents be limited to 1 year post-MI. It is also important to
      define clearly the endpoints of efficacy evaluations. A short-term reduction on
      markers like ventricular ectopic beats, for example, does not translate into a
      long-term decrease in arrhythmia-related mortality. Therefore, a reduction in
      overall mortality is the only meaningful endpoint to define the true risk-benefit
      ratio. To limit exposure to the potentially adverse effects of these agents,
      target populations for prophylactic antiarrhythmic drugs should be limited to
      recent post-MI patients at high risk for sudden cardiac death due to arrhythmia.
      Avoiding exposure of low-risk patients to antiarrhythmic drugs is equally
      imperative. "Low risk" of all-cause mortality includes the group of post-MI
      patients with a left ventricular ejection fraction >36%. Risk must be
      continuously evaluated in the setting of other pharmacologic (angiotensin
      converting enzyme [ACE] inhibitors, aspirin, 3-hydroxy-3-methylglutaryl coenzyme
      A reductase inhibitors ["statins"], and others) and/or nonpharmacologic
      interventions (coronary artery bypass graft, angioplasty, implantable
      cardioverter/defibrillator). There is also a need to improve noninvasive
      techniques for identifying patients in the high-risk category-at present, the
      presence of ventricular premature beats and a left ventricular ejection fraction
      <36% is considered somewhat predictive of sudden cardiac death. Thus, patients
      with a recent MI and moderately low left ventricular ejection fraction (< or =
      36% but not <20%) may be considered for antiarrhythmic therapy. A subset analysis
      of patients with low heart rate variability can provide valuable additional
      information. It is important to note that although all-cause mortality is a valid
      endpoint for such trials, stratification by specific cause of mortality is
      desirable.

PMID- 9537221
TI  - The azimilide post-infarct survival evaluation (ALIVE) trial.
AB  - The AzimiLide post-Infarct surVival Evaluation (ALIVE) trial is a new clinical
      trial using an innovative design to examine the potential of azimilide, a novel
      type of antiarrhythmic, for improving survival in post myocardial infarction (MI)
      patients at high risk of sudden cardiac death. Azimilide is the first of a unique
      class of antiarrhythmic drugs that blocks both slow and rapid components of the
      delayed rectifier potassium currents in human myocardium. Preclinical studies
      have shown the drug to be effective in reducing cardiac tachyarrhythmias, even
      under ischemic conditions. Currently, azimilide is in Phase III trials for the
      treatment of supraventricular arrhythmias. The ALIVE study design is based on
      lessons learned from the Cardiac Arrhythmia Suppression Trials (CAST), the
      Survival With Oral d-Sotalol (SWORD) trial, and the European Myocardial
      Infarction Amiodarone Trial (EMIAT) and identifies recent post-MI patients at
      high risk of sudden cardiac death. The hypothesis underlying this trial is that
      azimilide will improve survival in this patient population. The ALIVE trial is
      designed as a double-blind, placebo-controlled, multinational trial that will
      overcome the shortcomings of previous antiarrhythmic trials by using left
      ventricular ejection fraction and heart rate variability as predictors to target
      a post-MI patient population at high risk of sudden death. The major inclusion
      criteria for the study are adult patients of either gender with a left
      ventricular ejection fraction of 15-35% who have had a recent MI (within 6-21
      days). Additional stratification will be based on patients with heart rate
      variability < or = 20 U (heart rate variability index). Exclusion criteria
      include factors that may predispose a patient to nonarrhythmia-induced death or
      to low risk of sudden cardiac death caused by arrhythmia. Sample size is based on
      the assumption that the all-cause mortality rate (the primary endpoint) for 1
      year in placebo patients at high risk for sudden cardiac death (heart rate
      variability < or = 20 U) is 15% and that azimilide will decrease all-cause
      mortality by at least 45% in these patients. The trial consists of 3 groups
      patients receiving 75 mg azimilide orally each day, patients receiving 100 mg
      azimilide orally each day, and patients receiving placebo. No dose adjustments
      for age, gender, renal or hepatic failure, or concomitant use of warfarin or
      digoxin are thought necessary with azimilide. Enrollment for the trial is
      expected to continue for 24 months, and treatment is scheduled to be administered
      for a 1-year follow-up period.

PMID- 9537222
TI  - Azimilide dihydrochloride, a novel antiarrhythmic agent.
AB  - Azimilide, a novel class III antiarrhythmic agent, blocks both the slowly
      activating (IKs) and rapidly activating (IKr) components of the delayed rectifier
      potassium current, which distinguishes it from conventional potassium channel
      blockers such as sotalol and dofetilide, which block only IKr. Azimilide is being
      developed to prolong the time to recurrence of atrial fibrillation, atrial
      flutter, and paroxysmal supraventricular tachycardia in patients with and without
      structural heart disease. Azimilide is also being studied for its role in
      prevention of sudden cardiac death in high-risk patients after myocardial
      infarction (MI). Preclinical and clinical studies indicate that azimilide
      prolongs cardiac refractory period in a dose-dependent manner, as manifested by
      increases in action potential duration, QTc interval, and effective refractory
      period. Azimilide does not affect PR or QRS interval and minimally affects
      hemodynamic properties such as blood pressure and heart rate. Its in vivo effects
      appear to be rate-independent and are maintained under ischemic or hypoxic
      conditions, properties of potential clinical significance. Azimilide has shown
      excellent efficacy (>85%) in suppressing supraventricular arrhythmias in a
      variety of dog models. It also suppressed complex ventricular arrhythmias in
      infarcted dogs and, in a sudden death cardiac model, decreased mortality.
      Azimilide pharmacokinetics are very predictable. The drug is completely absorbed,
      and the extent of absorption is not affected by food. It can be administered once
      daily. Clinical data suggest that dose adjustments of azimilide are not required
      for age, gender, hepatic or renal function, or concomitant use of digoxin or
      warfarin. Azimilide has a good safety profile in open-label safety studies in
      >800 supraventricular arrhythmia patients, most with structural heart disease.
      The incidence of serious adverse events, including torsade de pointes, is low.
      The rate of patient withdrawal from long-term studies is also encouragingly low.
      Unlike amiodarone, azimilide has shown no evidence of pulmonary or ocular
      toxicity. Azimilide is expected to provide a unique new therapy for the
      prevention of supraventricular arrhythmias and sudden cardiac death when Phase
      III clinical trials are complete and safety and efficacy are confirmed.

PMID- 9537223
TI  - Regulation of E2F4 mitogenic activity during terminal differentiation by its
      heterodimerization partners for nuclear translocation.
AB  - E2F/DP heterodimers play a pivotal role in the regulation of cell growth and
      differentiation. A decrease in E2F/DP activity occurs during cell cycle arrest
      and differentiation. However, very little is known about the specific role of the
      various E2F/DP members along the transition from proliferation to terminal
      differentiation. We have previously shown that E2F4 accounts for the vast
      majority of the endogenous E2F in differentiating muscle cells. Here, we show
      that E2F4, which lacks a nuclear localization signal (nls), is distributed in
      both the nucleus and the cytoplasm, in either asynchronously growing myoblasts or
      differentiated myotubes. E2F4 nuclear accumulation is induced by the binding in
      the cytoplasm with specific partners p107, pRb2/p130, and DP3delta, an nls
      containing spliced form of DP3, which provide the nls. Although overexpression of
      E2F4/DP3delta reactivates the cell cycle in quiescent cells, the E2F4 nuclear
      accumulation induced by pRb2/p130 and p107 correlates with cell growth arrest
      Moreover, E2F4/DP3delta-induced cell cycle reactivation is efficiently
      counteracted by either p107 or pRb2/p130 overexpression. Reinduction in quiescent
      cells of DNA synthesis by E2F1/DP1 overexpression is abrogated by coexpression of
      pRb and is hampered by MyoD overexpression. Both pRb2/p130 and pRb, as well as
      MyoD, are up-regulated in myotubes. Accordingly, multinucleated myotubes, which
      are induced to reenter the S-phase by oncoviral proteins, are refractory to cell
      cycle reactivation by forced expression of E2F4/DP3delta or E2F1/DP1. Thus,
      E2F/DP repression represents only one of multiple redundant circuits that control
      the postmitotic state in terminally differentiated cells and that are targeted by
      adenovirus E1A and SV40 large T antigen.

PMID- 9537224
TI  - Amplification of the ATP-binding cassette 2 transporter gene is functionally
      linked with enhanced efflux of estramustine in ovarian carcinoma cells.
AB  - An estramustine-resistant human ovarian carcinoma cell line, SKEM, was generated
      to explore resistance mechanisms associated with this agent. Cytogenetic analysis
      revealed that SKEM cells have a homogeneously staining region (hsr) at chromosome
      9q34. Microdissection of the hsr, followed by fluorescence in situ hybridization
      to SKEM and normal metaphase spreads, confirmed that the amplified region was
      derived from sequences from 9q34. In situ hybridization with a probe specific for
      ABC2, a gene located at 9q34 that encodes an ATP-binding cassette 2 (ABC2)
      transporter, indicated that this gene is amplified approximately 6-fold in the
      estramustine-resistant cells. Southern analysis confirmed that ABC2 was amplified
      in SKEM, and Northern analysis indicated that the ABC2 transcript was
      overexpressed approximately 5-fold. The ABC1 gene located at 9q22-31 was not
      amplified in the resistant cells, and mRNA levels of several other ABC
      transporter genes were unaltered. Consistent with the concept that increased ABC2
      expression contributes to the resistant phenotype, we observed that the rate of
      efflux of dansylated estramustine was increased in SKEM compared with control
      cells. In addition, antisense treatment directed toward ABC2 mRNA sensitized the
      resistant cells to estramustine. Together, these results suggest that
      amplification and overexpression of ABC2 contributes to estramustine resistance
      and provides the first indication of a potential cellular function for this
      product.

PMID- 9537226
TI  - Mutations in the beta-catenin gene (CTNNB1) in endometrioid ovarian carcinomas.
AB  - Mutations of the beta-catenin gene (CTNNB1) have recently been implicated in the
      initiation of some colon carcinomas and melanomas. In these tumors, beta-catenin
      abnormally accumulates in the cell nuclei. In an ongoing immunohistochemical
      study of the cadherin-catenin complex protein expression in ovarian carcinomas,
      we observed beta-catenin in tumor cell nuclei in some cases; this prompted us to
      study whether or not this abnormal immunostaining pattern was due to mutation in
      the beta-catenin gene itself. This study examines beta-catenin
      immunohistochemical expression in 40 stage I and II ovarian borderline tumors and
      carcinomas of the most common histological types. Membrane expression was
      heterogeneous in all 40 cases. However, the cytoplasm and nucleus of five (one
      borderline tumor and four carcinomas) of the six endometrioid lesions contained
      beta-catenin expression. PCR and sequencing analyses of a 200-bp fragment of exon
      3 of the CTNNB1 gene, encompassing the sequence for glycogen synthetase kinase
      3beta phosphorylation, were performed in 11 tumors. Heterozygous substitution
      mutations at codon 37 in two cases (S37F and S37C) and at codon 41 in one case
      (T41A) were found in three endometrioid lesions (one borderline tumor and two
      carcinomas) with abnormal beta-catenin expression. Three endometrioid carcinomas
      and five tumors of other histological types analyzed showed normal DNA sequences.
      These results implicate beta-catenin gene mutations in ovarian malignant
      transformation with a characteristic phenotype: endometrioid ovarian carcinoma.

PMID- 9537225
TI  - Thymic lymphomas in mice with a truncating mutation in Brca2.
AB  - Inherited mutations in the BRCA2 gene predispose women to breast and ovarian
      cancer. We created a mutation in the mouse Brca2 gene that terminates translation
      in exon 11 at 45% of the normal transcript length. Ninety % of Brca2(tm1Cam)
      homozygous mutant mice die prenatally or perinatally. The location of the
      Brca2(tm1Cam) mutation differs from those reported previously, and this phenotype
      suggests a correlation with genotype analogous to that previously reported in
      humans. Although heterozygote mice have remained free of tumors for 10 months,
      Brca2(tm1Cam) homozygous mutants that survived to adulthood died with thymic
      lymphomas between 12 and 14 weeks of age.

PMID- 9537227
TI  - Expression of lumican in human breast carcinoma.
AB  - Lumican mRNA has been identified as being differentially expressed between
      different regions of the same human breast tumor. In situ hybridization study of
      26 independent breast tumors confirmed the presence of lumican mRNA in fibroblast
      like cells within stroma and showed a significant increase of its expression in
      tumor compared to adjacent normal stroma (P < 0.001). Higher lumican expression
      was associated with higher tumor grade, lower estrogen receptor levels in the
      tumor, and younger age of the patients (P < 0.05). Reverse transcription-PCR
      analysis of total RNA extracted from 19 independent breast tissues exhibiting
      lesions that are thought to parallel tumor progression also suggests that this
      proteoglycan is differentially expressed during tumor progression.

PMID- 9537228
TI  - Amplification, expression, and steroid regulation of the preprogalanin gene in
      human breast cancer.
AB  - The GALN gene encodes the preprogalanin protein that is cleaved to liberate the
      galanin peptide, a neuropeptide and tumor cell mitogen, and the galanin message
      associated peptide, which is of unknown function. GALN is located at chromosome
      11q13, a frequently amplified locus in diverse tumor types including breast
      cancer. To determine whether GALN may contribute to the tumor phenotype resulting
      from 11q13 amplification, we examined GALN amplification and preprogalanin mRNA
      levels in breast tumors and cell lines. GALN was amplified in a subset of breast
      tumors and cell lines that carried 11q13 amplifications. Preprogalanin mRNA was
      expressed in the majority of breast cancer cell lines, but Northern analysis
      failed to demonstrate a relationship between GALN amplification and preprogalanin
      mRNA levels. Eight of eight estrogen receptor-positive cell lines expressed
      detectable preprogalanin mRNA, and further investigation showed that
      preprogalanin mRNA was increased by treatment with estradiol and progestin and
      decreased by the removal of serum or treatment with antiestrogens. Thus, GALN
      amplification is unlikely to contribute to the phenotype conferred by 11q13
      amplification in breast cancer, but preprogalanin mRNA is expressed by breast
      cancer cells and is under steroid hormone control in estrogen receptor-positive
      cells, opening the wider question of the role of this steroid-regulated
      neuropeptide in the normal and cancerous breast.

PMID- 9537229
TI  - Adenoviral-mediated transfer of a heat-inducible double suicide gene into
      prostate carcinoma cells.
AB  - Tumor cells that express a fusion gene comprised of Escherichia coli cytosine
      deaminase (CD) and herpes simplex virus type 1 thymidine kinase (TK) sequences
      exhibit activation of and subsequent killing by the normally innocuous prodrugs 5
      fluorocytosine and ganciclovir (Rogulski et al., Hum. Gene Ther., 8: 73-85,
      1997). To target localized expression of this therapeutic gene, we have
      constructed a recombinant adenovirus containing the CD-TK fusion gene under the
      control of a human inducible heat shock protein 70 promotional sequence. Strong
      expression of the fusion gene product was induced by heating at 41 degrees C for
      1 h. Expression levels obtained were dependent on the multiplicity of infection
      used and the incubation time after heat shock. Heat-induced expression of the CD
      TK protein significantly reduced the survival of PC-3 cells in the presence of
      both 5-fluorocytosine and ganciclovir. These studies represent a novel form of
      gene therapy for the transduction and regulation of a double suicide gene in
      tumor cells and may provide a unique application for hyperthermia in cancer
      therapy.

PMID- 9537230
TI  - Human melanoma-specific, noncytolytic CD8+ T cells that can synthesize type I
      cytokine.
AB  - The existence of CD8+ CTLs that are capable of recognizing MHC class I-bound,
      human tumor-associated peptide antigens is now unequivocally documented in cancer
      patients. Thus far, the role of CD8+ T cells in tumor immunity has been
      predominantly viewed in terms of cytolytic ability as the prime mode of their
      function. Interestingly, it is increasingly evident that CD8+ T cells are capable
      of synthesizing both type I and type II cytokines. Thus, it is conceivable that
      tumor antigen-specific but noncytolytic CD8+ T cells might play an important role
      in antitumor immune response by synthesizing type I cytokine. Through such
      cytokines, they could provide "help" for the process of generating as well as in
      maintaining an effective CD8+ CTL response. In addition, they might recruit other
      types of effector cells (such as natural killer cells, macrophages, and others)
      locally at the tumor site. Either way, they could exert a profoundly positive
      role in cell-mediated antitumor immune response, particularly because the great
      majority of tumor cells express only MHC class I molecules that present peptide
      epitopes to CD8+ T cells. Unfortunately, tumor antigen-specific, noncytolytic but
      type I cytokine-secreting CD8+ T cells have not received much investigative
      attention. Here we show that CD8+ T cells, isolated from the tumor-infiltrating
      lymphocytes from human melanoma, synthesize type I cytokine (IFN-gamma and tumor
      necrosis factor alpha) in a MHC class I-restricted and tumor-specific
      noncytolytic interaction with the autologous melanoma cells.

PMID- 9537231
TI  - BRCA2 germ-line mutations are frequent in male breast cancer patients without a
      family history of the disease.
AB  - Breast cancer is a rare disease in men, affecting less than 0.1% of the male
      population. Two heritable gene defects have been associated with a predisposition
      to male breast cancer development, ie., germ-line mutations in the breast cancer
      susceptibility gene BRCA2 and the androgen receptor (AR) gene. In this study, the
      entire coding regions of BRCA2 and AR were screened for mutations in 34
      consecutive male breast cancer patients. Five different truncating BRCA2
      mutations were identified in 7 (21%) of the 34 cases, with all mutations being of
      germ-line origin. Three of the mutated cases carried the same mutation
      (4186delG), which has been found earlier in two Swedish families with multiple
      female breast cancer cases. Haplotype analysis supported a common ancestry of
      4186delG. One mutation, 6503delTT, was found in a male carrying also a previously
      identified COOH-terminal polymorphic stop codon (Lys3326ter). No differences were
      seen between mutation carriers and noncarriers with respect to clinical stage and
      estrogen or progesterone receptor status. Mutation carriers tended to be younger
      at diagnosis. No germ-line AR mutations were found in the present material, but
      the number of AR polyglutamine repeats tended to be lower among mutation
      carriers. Most surprisingly, only one of the seven BRCA2 mutation carriers had a
      positive family history of breast cancer, suggesting a lower penetrance of some
      BRCA2 mutations or an influence of modifying factors for disease development in
      males and females. The present study implies that approximately one-fifth of all
      male breast cancer cases in the Swedish population are due to germ-line BRCA2
      mutations.

PMID- 9537232
TI  - A large deletion disrupts the exon 3 transcription activation domain of the BRCA2
      gene in a breast/ovarian cancer family.
AB  - We describe the identification of a large deletion in the BRCA2 gene as the
      disease-causing mutation in a Swedish breast/ovarian cancer family. The 5068-bp
      deletion encompassed the 3' region of exon 3, including the 3' splice site and
      most of intron 3, and it resulted on the mRNA level in an inframe exon 3
      skipping. The junction site also included an insertion of 4 bp (CCAT). The
      mutation (nt504del5068insCCAT) resulted in a genotype absent of the two
      transcription activation regions localized to exon 3. The breast cancer phenotype
      associated with the described mutation resembled the phenotype of breast cancer
      found in both BRCA1 and BRCA2 mutation carriers. This is the first report of a
      large deletion as the disease-causing mutation in the BRCA2 gene.

PMID- 9537233
TI  - The role of ataxia-telangiectasia heterozygotes in familial breast cancer.
AB  - The role of ataxia-telangiectasia (AT) heterozygotes in breast cancer has been
      controversial. We have found previously an overrepresentation (3.4%) of ATM
      mutations in a subset of 88 selected breast cancer patients with a family history
      of breast cancer, leukemia, and lymphoma. This prevalence is comparable to the
      estimated value (3.8%) from epidemiological study. To further examine the
      possibility that ATM is correlated to breast cancer, we screened for ATM germ
      line mutations in another 100 breast cancer patients with a family history of
      breast cancer. We used the protein truncating test and found one new germ-line
      mutation. This figure (1%) is consistent with the observed 0.2-1% carrier
      frequency for AT. We also studied breast tumors from ATM mutants, and three
      showed retention of both alleles, whereas the fourth showed loss of the mutant
      allele. We conclude that the contribution of heterozygous ATM mutations to
      familial breast cancer is minimal. Even if the ATM gene were causative in these
      cases, it is not likely to act as a tumor suppressor.

PMID- 9537234
TI  - Search for mutations and examination of allelic expression imbalance of the p73
      gene at 1p36.33 in human lung cancers.
AB  - We examined 61 lung cancer cases to determine whether alterations of p73, a novel
      monoallelically expressed p53-like molecule, may be involved in the pathogenesis
      of lung cancer. Allelic loss at the p73 locus at 1p36.33 was observed in 42% (11
      of 26 informative cases), and squamous cell carcinoma tended to carry this lesion
      most frequently. Somatic mutations in the p73 gene itself, however, were not
      detected, despite our extensive search. We found interindividual difference in
      the allelic expression of p73 in normal lung, as well as intertissue variance,
      even within the same individual, but preferential loss of the expressed allele
      appeared to be an unlikely mechanism for p73 inactivation. This study,
      consequently, suggests the presence of an as yet unidentified tumor suppressor
      gene or genes within the subtelomeric region of 1p, warranting further studies
      aimed at its isolation.

PMID- 9537235
TI  - Low frequency of somatic mutations in the LKB1/Peutz-Jeghers syndrome gene in
      sporadic breast cancer.
AB  - Germ-line mutations in the LKB1 gene on chromosome 19p are responsible for most
      cases of the Peutz-Jeghers syndrome, in which intestinal hamartomas are
      associated with elevated risks of several cancer types, including breast cancer.
      We have evaluated the role of somatic mutations in LKB1 in breast cancer. Of 40
      informative primary breast cancers, 3 showed loss of heterozygosity on chromosome
      19p in the vicinity of LKB1, and no somatic mutations of LKB1 were observed in 62
      primary breast cancers and 17 established breast cancer cell lines. The results
      indicate that mutations in LKB1 do not play an important role in the development
      of sporadic breast cancer.

PMID- 9537236
TI  - Linkage of familial Wilms' tumor predisposition to chromosome 19 and a two-locus
      model for the etiology of familial tumors.
AB  - Familial predisposition to Wilms' tumor (WT), a childhood kidney tumor, is
      inherited as an autosomal dominant trait. For most WT families studied, the 11p13
      gene WT1 and genomic regions implicated in tumorigenesis in a subset of tumors
      can be ruled out as the site of the familial predisposition gene. Following a
      genome-wide genetic linkage scan, we have obtained strong evidence (log of the
      odds ratio = 4.0) in five families for an inherited WT predisposition gene (FWT2)
      at 19q13.3-q13.4. In addition, we observed loss of heterozygosity at 19q in
      tumors from individuals from two families in which 19q can be ruled out as the
      site of the inherited predisposing mutation. From these data, we hypothesize that
      alterations at two distinct loci are critical rate-limiting steps in the etiology
      of familial WTs.

PMID- 9537237
TI  - Down-regulation of homeobox gene GBX2 expression inhibits human prostate cancer
      clonogenic ability and tumorigenicity.
AB  - Previously, we have demonstrated that GBX genes, a homeobox-containing human
      family of DNA-binding transcription factors consisting of GBX1 and GBX2, are
      overexpressed in a panel of human prostatic cancer cell lines (ie., TSU-pr1, PC3,
      DU145, and LNCaP) compared to normal prostate. In the present studies, specific
      primer sets were designed for reverse transcription-PCR detection of the
      expression of GBX1 versus GBX2 in human prostate cancer. These studies
      demonstrated that the GBX2 gene, but not the GBX1 gene, is consistently
      overexpressed in this panel of human prostate cancer cell lines compared to
      normal human prostate. Using a quantitative-competitive PCR analysis, GBX2 mRNA
      was expressed as 3 x 10(3) copies/microg RNA in normal prostate tissue and 4 x
      10(4) copies/microg RNA in the immortalized normal neonatal prostate epithelial
      cell line 267B-1, as compared to 6 x 10(5), 5 x 10(5), 3 x 10(5), and 1 x 10(5)
      copies/microg RNA in TSU-pr1, DU145, LNCaP, and PC3 prostate cancer cell lines,
      respectively. To examine the importance of GBX2 expression for prostate cancer
      malignancy, GBX2-overexpressing TSU-pr1 and PC3 human prostatic cancer cells were
      transfected with a eukaryotic expression vector containing an antisense GBX2
      homeobox domain cDNA. Stable transfectant clones with 5-10-fold decreased levels
      of GBX2 mRNA expression were obtained. When tested in vitro, the clonogenic
      ability of the GBX2 antisense transfectants was reduced by approximately 50% in
      both cell lines. When implanted s.c. into nude mice, the tumorigenicity of the
      antisense GBX2 transfectants from both human prostatic cancer cell lines was
      inhibited by more than 70% compared to the parental cells. These results suggest
      that expression of GBX2 gene is required for malignant growth of human prostate
      cells.

PMID- 9537238
TI  - Increased incidence of matrix metalloproteinases in urine of cancer patients.
AB  - Matrix metalloproteinases (MMPs) have been implicated in mechanisms of metastasis
      in experimental cancer models and in human malignancies. In this study, we used
      substrate gel electrophoresis (zymography) to determine the frequency of
      detection of MMPs in urine of patients with a variety of cancers. Three molecular
      weight classes of urinary MMPs, Mr 72,000, Mr 92,000, and high molecular weight
      (Mr > or = 150,000) species, were detected reproducibly and correlated with
      disease status. The Mr 72,000 and Mr 92,000 species were identified as MMP-2 and
      MMP-9, respectively, by Western blot analysis. The presence of biologically
      active MMP-2 (P < 0.001) or MMP-9 (P = 0.002) was an independent predictor of
      organ-confined cancer, and the high molecular weight species (P < 0.001) was an
      independent predictor of metastatic cancer. This is the first study to
      demonstrate that analysis of urinary MMPs may be useful in determining disease
      status in a variety of human cancers, both within and outside of the urinary
      tract.

PMID- 9537239
TI  - DNA interstrand cross-links induced by psoralen are not repaired in mammalian
      mitochondria.
AB  - Although it is generally known that mitochondria are defective in DNA damage
      processing, little is known about the DNA repair pathways and mechanisms that
      exist in these vital organelles. Certain lesions that are removed by base
      excision repair are efficiently removed in mitochondria, whereas some bulky
      lesions that are removed by nucleotide excision repair are not repaired in these
      organelles. There has been much interest in whether mitochondria possess
      activities for recombination repair, and some previous studies have reported such
      activities, whereas others have not. We have taken the approach of studying the
      formation and removal of interstrand cross-links (ICLs) in DNA. These lesions are
      thought to be repaired by a repair mechanism that involves nucleotide excision
      and recombinational repair. The formation and repair of DNA ICLs by 4'
      hydroxymethyl-4,5',8-trimethylpsoralen was investigated in both the nuclear and
      mitochondrial genomes in hamster cells. Seven-fold-higher levels of ICLs were
      generated in mtDNA than in the dihydrofolate reductase gene, clearly indicating
      that the mitochondrial genome is a preferential target of 4'-hydroxymethyl-4,5',8
      trimethylpsoralen damage. ICLs were removed efficiently from the dihydrofolate
      reductase gene, but no repair was observed in mtDNA. Our observations support
      previous work showing efficient gene-specific repair of these lesions in the
      nucleus but suggest that repair of this type of ICL does not exist in the
      mitochondria. The preferential damage of mtDNA and the absence of cross-link
      repair further suggests that mtDNA may be a biologically important target for
      psoralen.

PMID- 9537240
TI  - Molecular detection of genetic alterations in the serum of colorectal cancer
      patients.
AB  - We have searched for the presence of genetic alterations in serum DNA obtained
      from 44 colorectal cancer patients. Microsatellite analysis using highly
      polymorphic markers revealed loss of heterozygosity and/or microsatellite
      instability in 35 of 44 (80%) primary tumors. No alterations were detected in the
      paired serum DNA. We next used an oligonucleotide-mediated mismatch ligation
      assay to detect tumor specific gene mutations in the serum. Among the 16 cases
      with a K-ras gene mutation in the tumor, the same mutation was detected in three
      paired serum samples. In the 10 cases with a p53 mutation in the tumor, the
      identical mutation was detected in seven corresponding serum samples. Comparison
      of the molecular analysis with clinical diagnosis of these patients revealed that
      none of the seven Dukes' stage B patients with a K-ras mutation in their tumors
      demonstrated a mutation in the serum. In contrast, five of seven stage B patients
      with a p53 mutation in the tumor demonstrated a mutation in the paired serum (P =
      0.01, Fisher's exact test). Taken together, either a K-ras or p53 mutation was
      detected in the serum in 40% of the 25 patients (95% confidence interval, 21
      61%), whose primary tumors contained a mutation and in 23% of the 44 patients
      (95% confidence interval, 12-38%) with colorectal cancer. The frequent detection
      of p53 mutation in the serum of patients with early stage tumors suggests a
      possible use of this approach for clinical prognosis and cancer monitoring of
      colorectal cancer patients.

PMID- 9537241
TI  - The unique physiology of solid tumors: opportunities (and problems) for cancer
      therapy.
AB  - The physiology of solid tumors differs from that of normal tissues in a number of
      important aspects, the majority of which stem from differences between the two
      vasculatures. Compared with the regular, ordered vasculature of normal tissues,
      blood vessels in tumors are often highly abnormal, distended capillaries with
      leaky walls and sluggish flow. Tumor growth also requires continuous new vessel
      growth, or angiogenesis. These physiological differences can be problems for
      cancer treatment; for example, hypoxia in solid tumors leads to resistance to
      radiotherapy and to some anticancer drugs. However, these differences can also be
      exploited for selective cancer treatment. Here we review four such areas that are
      under active investigation: (a) hypoxia-selective cytotoxins take advantage of
      the unique low oxygen tension in the majority of human solid tumors.
      Tirapazamine, a drug in the final stages of clinical trials, is one of the more
      promising of these agents; (b) leaky tumor blood vessels can be exploited using
      liposomes that have been sterically stabilized to have a long intravascular half
      life, allowing them to selectively accumulate in solid tumors; (c) the tumor
      microenvironment is a stimulus to angiogenenesis, and inhibition of angiogenesis
      can be a powerful anticancer therapy not susceptible to acquired drug resistance;
      and (d) we discuss attempts to use gene therapy activated either by the low
      oxygen environment or by necrotic regions of tumors.

PMID- 9537242
TI  - A relevant dose of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone is extensively
      metabolized and rapidly absorbed in the canine tracheal mucosa.
AB  - Lung cancer is largely a site-of-entry disease caused by inhaled carcinogenic
      agents, especially tobacco smoke. Two major groups of procarcinogens, tobacco
      specific nitrosamines and polycyclic aromatic hydrocarbons, are putative agents,
      but their relative contributions are disputed. An important indicator of relative
      potency for these compounds is the dose to the target epithelial cells. Although
      we have reported the dose of polycyclic aromatic hydrocarbons to the canine
      tracheal epithelium [Gerde et al., Carcinogenesis (Lond.), 18: 1825-1832, 1997;
      Gerde et al., Carcinogenesis (Lond.), in press, 1998], the purpose of the current
      study was to characterize the absorption and metabolism of low levels of one
      tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone
      (NNK), in the canine trachea. One hundred ng of tritiated NNK were instilled in
      the distal trachea of the dog. Blood was repeatedly sampled from the azygous vein
      and both sides of the systemic circulation from 15 s to 30 min after
      instillation. Tissues were then removed and analyzed for the tritiated NNK and
      its metabolites. Autoradiography was used to determine the depth distribution of
      tritium in the tracheal mucosa. Most NNK appeared rapidly in the blood draining
      the airway mucosa, but there was also a slow clearance phase. During absorption,
      NNK was distributed within the entire depth of the mucosa to the tracheal
      cartilage; however, a portion was conspicuously bound to the mucin component of
      the mucous lining layer. Reversible binding to mucin may be largely responsible
      for the slow clearance phase. Despite the rapid absorption of most of the
      tritium, NNK was nonetheless extensively metabolized in the tracheal mucosa.
      Systemic metabolism was also rapid: within 18 min of instillation, the NNK parent
      compound had disappeared from the systemic circulation, and 45 min after
      instillation, no NNK was found in the trachea or any distal tissue. Although the
      rapid absorption and distribution of NNK and its metabolites ensured widespread
      and extensive distal binding in all tissues, first-pass metabolism and activation
      of NNK in the airway mucosa were sufficiently rapid to cause levels of binding at
      the site of absorption to be approximately 20-fold those of distal tissues. NNK
      may thus act as a site-of-entry carcinogen. This observation may be important in
      estimating the contribution of NNK to lung cancer relative to other carcinogens
      and for explaining increased incidences of oral cancers in users of snuff and
      chewing tobacco in which NNK is present in high concentrations.

PMID- 9537243
TI  - Differential selectivity of ligands for the C1a and C1b phorbol ester binding
      domains of protein kinase Cdelta: possible correlation with tumor-promoting
      activity.
AB  - Protein kinase C (PKC) represents the major, high-affinity receptor for the
      phorbol esters as well as for a series of structurally diverse natural products.
      The phorbol esters function by binding to the tandem C1a and C1b domains in PKC,
      leading to enzyme activation. Although the typical phorbol esters represent the
      paradigm for tumor promoters in mouse skin, it is now clear that different high
      affinity ligands for PKC have distinct biological effects. Thus, the daphnane
      analogue mezerein is a second-stage promoter, the macrolide bryostatin 1 is a
      partial antagonist, and certain 12-deoxyphorbol 13-monoesters also function as
      partial antagonists but with a different pattern of activity. The biochemical
      basis for these differences is an area of active investigation. In this report,
      we have examined the relative interaction of ligands differing in structure and
      pattern of biological response with the C1a and C1b domains of PKCdelta. We
      mutated either or both of the C1 domains of PKCdelta, expressed the constructs in
      NIH 3T3 cells, and monitored the interaction of the ligands by their ability to
      induce translocation of the mutated PKCdelta from the cytosol to the particulate
      fraction. We found that different ligands showed different dependence on the C1a
      and C1b domains for translocation. Whereas phorbol 12-myristate 13-acetate and
      the indole alkaloids indolactam and octylindolactam were selectively dependent on
      the C1b domain, selectivity was not observed for mezerein, for the 12
      deoxyphorbol 13-monoesters prostratin or 12-deoxyphorbol 13-phenylacetate, or for
      the macrocyclic lactone bryostatin 1. Provocatively, the pattern of response
      corresponds with the activity of the compounds as complete tumor promoters.

PMID- 9537244
TI  - Overexpression of the myristoylated alanine-rich C kinase substrate in human
      choroidal melanoma cells affects cell proliferation.
AB  - Reduced expression of the myristoylated alanine-rich C kinase substrate (MARCKS)
      has been described in various cell lines after oncogenic or chemical
      transformation, leading to the question of whether this protein may be involved
      in cell proliferation. Here we compare the expression of MARCKS in human tumor
      derived choroidal melanoma cells (OCM-1) and in primary cultures of normal
      choroidal melanocytes. We found an important down-regulation of the protein in
      the melanoma cell line. Stable transfection of these cells with the cDNA coding
      for MARCKS led to the selection of several clones expressing variable levels of
      the protein. Proliferation experiments performed with four of these clones
      revealed that cell growth was reduced by 35-40% when compared with control cells.
      Upon serum starvation, cell proliferation was almost abolished when the
      expression level of MARCKS was high, whereas it was only partially reduced in the
      controls. MARCKS overexpression induced a higher percentage of cells in the G0-G1
      phase of the cell cycle upon serum starvation, as well as the inhibition of
      colony formation in soft agar. Finally, the expression of the CDK inhibitor p27
      was increased in the cells presenting a high level of MARCKS protein. Altogether,
      these data suggest that the expression of this protein kinase C substrate affects
      the proliferation and partially reverts the transformed phenotype of the OCM-1
      cells.

PMID- 9537245
TI  - Topical retinoic acid reduces skin papilloma formation but resistant papillomas
      are at high risk for malignant conversion.
AB  - Retinoic acid (RA) was topically applied to the skin of Sencar mice during the
      promotion phase of specific tumor induction protocols that produce papillomas at
      low (12-O-tetradecanoylphorbol-13-acetate promoted, TPA) or high (mezerein
      promoted) risk for premalignant progression and malignant conversion. RA
      consistently reduced the yield of papillomas and carcinomas in both protocols,
      but the frequency of malignant conversion in papillomas that emerged during RA
      treatment was not reduced. When TPA was reapplied after cessation of RA
      treatment, the number of papillomas increased 2-fold, suggesting that RA had not
      eliminated initiated cells. In vitro, RA prevented the emergence of transformed
      keratinocytes in an assay that mimics malignant conversion, suggesting that RA
      can suppress conversion if applied during the stage of premalignant progression.
      Examination of tumor markers at weeks 14 and 22 of the tumor-induction
      experiments in vivo indicated that papillomas evolving during RA treatment
      exhibited a phenotype of high progression risk, even in the TPA-promoted groups.
      In the majority of these tumors, the alpha6beta4 integrin and retinoid X receptor
      alpha transcripts were detected suprabasally, indicating an advanced state of
      premalignant progression. RA-treated tumors also expressed higher levels of
      transcripts for transforming growth factor (TGF)-beta1 and localized TGF-beta1
      peptide in the basal portions of the tumor fronds. Because up-regulated
      expression of TGF-beta1 suppresses papilloma formation, these studies suggest a
      mechanism whereby RA can prevent papilloma eruption via a TGF-beta intermediate,
      but papillomas resistant to RA may have altered TGF-beta signaling and progress
      to carcinomas at an increased frequency.

PMID- 9537246
TI  - Differential expression of methionine adenosyltransferase genes influences the
      rate of growth of human hepatocellular carcinoma cells.
AB  - Methionine adenosyltransferase (MAT) catalyzes the formation of S
      adenosylmethionine (SAM), the principal methyl donor, and is essential to normal
      cell function. The two forms of MAT, liver specific and non-liver specific, are
      products of two genes, MAT1A and MAT2A, respectively. We have reported a switch
      from MAT1A to MAT2A gene expression in human liver cancer cells. In the current
      work, we examined whether the type of MAT expressed by the cell influences cell
      growth. HuH-7 cells were stably transfected with MAT1A and were subsequently
      treated with antisense oligonucleotides directed against MAT2A. MAT2A antisense
      treatment reduced the amount of MAT2A mRNA by 99% but had no effect on MAT1A
      mRNA. Cell growth and DNA synthesis rates were reduced by approximately 20-25%
      after transfection with MAT1A and by an additional 30-40% after MAT2A antisense
      treatment. SAM level and SAM:S-adenosylhomocysteine (SAH) ratio increased by 50
      75% after MAT1A transfection and by an additional 60-80% after MAT2A antisense
      treatment. DNA methylation changed in parallel to changes in SAM level and
      SAM:SAH ratio. Supplementing untransfected HuH-7 cells with SAM in the culture
      medium increased SAM level, SAM:SAH ratio, and DNA methylation and decreased cell
      growth and DNA synthesis. In conclusion, cell growth is influenced by the type of
      MAT expressed. The mechanism likely involves changes in SAM:SAH ratio and DNA
      methylation.

PMID- 9537247
TI  - Prognostic value of P53 gene mutations in a large series of node-negative breast
      cancer patients.
AB  - The most important subgroup of breast cancer patients for which reliable
      prognostic factors are needed are women without axillary lymph node involvement.
      Although overall, these patients have a good prognosis, it is known that 20-30%
      will experience a recurrence of the disease. To determine the prognostic
      significance of P53 tumor suppressor gene mutation, specimens from 113 primary
      breast cancers were evaluated for the presence of P53 alterations, as detected by
      cDNA sequencing of the entire coding sequence of the gene. The median follow-up
      for patients was 105 months. P53 gene mutation was an independent prognostic
      marker of early relapse and death. Our results suggest that P53 gene mutations
      could be an important factor to identify node-negative patients who have a poor
      prognosis in the absence of adjuvant therapy. Prospective studies should be
      designed to determine which therapy should be performed in this subgroup of
      patients.

PMID- 9537248
TI  - Combined nested RT-PCR assay for prostate-specific antigen and prostate-specific
      membrane antigen in prostate cancer patients: correlation with pathological
      stage.
AB  - Nested reverse transcription (RT)-PCR for prostate-specific antigen (PSA) and
      prostate-specific membrane antigen (PSM) can detect circulating prostatic cells
      in patients with prostate cancer. We evaluated the role of a combined screening
      approach for PSA and PSM in prostate cancer staging. We examined the peripheral
      blood samples from 136 patients with adenocarcinoma of the prostate (PCA), 15
      patients with benign prostatic hyperplasia, 15 normal male subjects, and 5 female
      subjects. The controls (benign prostatic hyperplasias, normal males, and normal
      females) were negative for both PSA and PSM. In patients with metastatic PCA (n =
      11), 100% were positive by combined PSA/PSM (64% by PSA and 91% by PSM). In
      biochemical failure PCA patients (n = 18), 39% were positive by PSM, compared to
      only 6% by PSA. In patients with clinically localized PCA (n = 107), 48% were
      positive by combined PSA/PSM approach (43% by PSM and 14% by PSA). These results
      show that PSM is a more sensitive marker than PSA in detecting circulating
      prostatic cells (P < 0.0001). We correlated preoperative RT-PCR results with
      final pathological stages in 67 prostatectomy patients. RT-PCR positivity was
      81.5% in patients with non-organ-confined disease versus 37.5% in organ-confined
      disease (P = 0.001). PSA/PSM RT-PCR had an odds ratio of 7.3 (95% confidence
      interval, 2.3-23.4; P = 0.001) in predicting tumor extracapsular extension.
      PSA/PSM RT-PCR was a better predictor of tumor extracapsular extension than
      initial serum PSA, clinical stage, and biopsy Gleason score. Our data show that
      PSA/PSM nested RT-PCR may provide the staging information unavailable from the
      current modalities. The ultimate impact of this technique in the management of
      patients with prostate cancer will require continued investigation.

PMID- 9537249
TI  - Chinese hamster ovary cells resistant to the topoisomerase II catalytic inhibitor
      ICRF-159: a Tyr49Phe mutation confers high-level resistance to
      bisdioxopiperazines.
AB  - Anticancer drugs targeted to the nuclear enzyme DNA topoisomerase II are
      classified as poisons that lead to DNA breaks or catalytic inhibitors that appear
      to completely block enzyme activity. To examine the effects of the
      bisdioxopiperazine class of catalytic inhibitors to topoisomerase II, we
      investigated a Chinese hamster ovary (CHO) subline selected for resistance to
      ICRF-159 (CHO/159-1). Topoisomerase IIalpha content in CHO/159-1 cells was
      reduced by 40-50%, compared to wild-type CHO cells, whereas the beta isoform was
      increased by 10-20% in CHO/159-1 cells. However, the catalytic activity of
      topoisomerase II in nuclear extracts from CHO/159-1 cells was unchanged, as was
      its inhibition by the topoisomerase II poison etoposide (VP-16). No inhibition of
      topoisomerase II catalytic activity by ICRF-187 was seen in CHO/159-1 cells up to
      500 microM, whereas inhibition was evident at 50 microM in wild-type CHO cells.
      VP-16-mediated DNA single-strand breaks and cytotoxicity were similar in the two
      sublines. ICRF-187 could abrogate these VP-16 effects in the wild-type line but
      had no effect in CHO/159-1 cells. Western blots of topoisomerase IIalpha after
      incubation of CHO cells with ICRF-187 demonstrated a marked band depletion,
      whereas this effect was completely lacking in CHO/159-1 cells, and an equal
      effect of VP-16 was observed in both lines. These data imply that the CHO/159-1
      topoisomerase IIalpha lacks sensitivity to bisdioxopiperazines and that the
      mechanism of resistance in this cell line does not confer cross-resistance to
      topoisomerase II poisons, suggesting that mutations conferring resistance to
      bisdioxopiperazines can occur at sites distinct from those responsible for
      resistance to complex stabilizing agents. Accordingly, CHO/159-1 cDNA showed two
      heterozygous mutations in the proximal NH2-terminal part of topoisomerase IIalpha
      (Tyr49Phe and delta 309Gln-Gln-Ile-Ser-Phe313), which is in contrast to those
      induced by topoisomerase II poisons, which cluster further downstream. Site
      directed mutagenesis and transformation of the homologous Tyr50Phe coding
      mutation in human topoisomerase IIalpha in a temperature-conditional yeast system
      demonstrated a high-level resistance to ICRF-193, compared to cells expressing
      wild-type cDNA, but none toward the poisons VP-16 or amsacrine, thus confirming
      that the Tyr50Phe mutation confers specific resistance to bisdioxopiperazines.
      Thus, these results indicate that the region of the protein involved in ATP
      binding also plays a critical role in sensitivity to bisdioxopiperazines, a
      result consistent with the known requirement for the formation of an ATP-bound
      closed clamp for bisdioxopiperazine activity. These results may enable a more
      precise understanding of the interaction of topoisomerase II-directed drugs with
      their target enzyme.

PMID- 9537250
TI  - Mice transgenic for human carcinoembryonic antigen as a model for immunotherapy.
AB  - Mice transgenic for the human carcinoembryonic antigen (CEA) gene were prepared
      for use as a preclinical model for immunotherapy. A 32.6-kb fragment containing
      the complete human CEA gene and flanking sequences was isolated from a genomic
      cosmid clone and used to produce transgenic C57BL/6 mice. A homozygous line was
      established that was designated C57BL/6J-TgN(CEAGe)18FJP. Southern blot analysis
      showed that this line contained intact copies of the cosmid clone, with
      approximately 19 integrated copies at one chromosomal location. A mouse-human
      chimeric anti-CEA monoclonal antibody was used to examine CEA expression by
      immunohistochemical staining of frozen tissue sections. In the cecum and colon,
      approximately 20% of the luminal epithelial cells had strong cytoplasmic
      staining, whereas occasional glands showed intense staining. CEA was also
      expressed in gastric foveolar cells, whereas small intestine villi had only a few
      (<1%) positive cells. CEA was not found by immunohistochemistry in other tissues
      of the digestive tract, nor was it found in a wide range of other tissues or
      organs. Concordance in results was obtained between immunohistochemistry and
      analysis of tissue extracts by enzyme immunoassay. The lone exception was the
      testis, which was positive only by enzyme immunoassay. Expression of human CEA
      was not observed in tissues derived from nontransgenic mice. The fecal content of
      CEA in transgenic mice was approximately 100-fold less than that observed for
      humans. Circulating CEA was not detected. A CEA-transfected syngeneic murine
      colon carcinoma cell line, MC-38, was prepared that had stable expression of CEA
      in vitro and in vivo. The molecular size of CEA produced by CEA-transfected MC-38
      cells and by the colon of transgenic mice was similar to that obtained with CEA
      purified from human colon tumors. Anti-CEA antibody appeared in nontransgenic but
      not transgenic mice bearing transfected MC-38 tumors. These findings demonstrate
      that CEA distribution and its properties in tissues of mice transgenic for the
      human CEA gene are similar to that observed in human tissues. As in humans,
      immune responsiveness to CEA, as reflected by antibody formation, was not
      detectable in transgenic mice bearing CEA-positive tumors. Thus, CEA transgenic
      mice may serve as a useful model for studying the efficacy and safety of various
      immunotherapy strategies directed at this tumor self-antigen.

PMID- 9537251
TI  - Interleukin 2 expression by tumor cells alters both the immune response and the
      tumor microenvironment.
AB  - Microenvironmental conditions within solid tumors can have marked effects on the
      growth of the tumors and their response to therapies. The disorganized growth of
      tumors and their attendant vascular systems tends to result in areas of the
      tumors that are deficient in oxygen (hypoxic). Cells within these hypoxic areas
      are more resistant to conventional therapies such as radiation and chemotherapy.
      Here, we examine the hypoxic state of EMT6 mouse mammary tumors and the location
      of host cells within the different areas of the tumors to determine whether such
      microenvironmental conditions might also affect their ability to be recognized by
      the immune system. Hypoxia within tumors was quantified by flow cytometry and
      visualized by immunohistochemistry using a monoclonal antibody (ELK3-51) against
      cellular adducts of 2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3
      pentafluoropropyl)acetam ide (EF5), a nitroimidazole compound that binds
      selectively to hypoxic cells. Thy-1+ cells, quantified using a monoclonal
      antibody, were found only in the well-oxygenated areas. The location of these Thy
      1+ cells was also examined in EMT6 tumors that had been transfected with the gene
      for interleukin-2 (IL-2) because these tumors contain greatly increased numbers
      of host cells. Surprisingly, we found that IL-2-transfected tumors had
      significantly decreased hypoxia compared to parental tumors. Furthermore, using
      the fluorescent dye Hoechst 33342, an in vivo marker of perfused vessels,
      combined with immunochemical staining of PECAM-1 (CD31) as a marker of tumor
      vasculature, we found increased vascularization in the IL-2-transfected tumors.
      Thus, expression of IL-2 at the site of tumor growth may enhance tumor immunity
      not only by inducing the generation of tumor-reactive CTLs but also by allowing
      increased infiltration of activated T cells into the tumors.

PMID- 9537252
TI  - Reduction of established spontaneous mammary carcinoma metastases following
      immunotherapy with major histocompatibility complex class II and B7.1 cell-based
      tumor vaccines.
AB  - For many cancer patients, removal of primary tumor is curative; however, if
      metastatic lesions exist and are not responsive to treatment, survival is
      limited. Although immunotherapy is actively being tested in animal models against
      primary tumors and experimental metastases (i.v. induced), very few studies have
      examined immunotherapy of spontaneous, established metastatic disease. The
      shortage of such studies can be attributed to the paucity of adequate animal
      models and to the concern that multiple metastatic lesions may be more resistant
      to immunotherapy than a localized primary tumor. Here, we use the BALB/c-derived
      mouse mammary carcinoma, 4T1, and show that this tumor very closely models human
      breast cancer in its immunogenicity, metastatic properties, and growth
      characteristics. Therapy studies demonstrate that treatment of mice with
      established primary and metastatic disease with MHC class II and B7.1-transfected
      tumor cells reduces or eliminates established spontaneous metastases but has no
      impact on primary tumor growth. These studies indicate that cell-based vaccines
      targeting the activation of CD4+ and CD8+ T cells may be effective agents for the
      treatment of malignancies, such as breast cancer, where the primary tumor is
      curable by conventional methods, but metastatic lesions remain refractile to
      current treatment modalities.

PMID- 9537253
TI  - Clinicopathological significance of altered loci of replication error and
      microsatellite instability-associated mutations in gastric cancer.
AB  - Replication errors (RERs) judged by microsatellite instability and its associated
      mutations have been recognized as an important mechanism in tumorigenesis of
      gastric cancers (GCs). To gain a deeper insight into its significance, we
      examined the frequency of RERs using nine microsatellite markers and screened
      mutations in the polydeoxyadenine tract of the transforming growth factor beta
      type II receptor gene (TGF-betaRII) and polydeoxyguanine tracts of insulin-like
      growth factor II receptor and BAX genes. Twenty-four (30%) of 80 patients with GC
      had RERs, of which 3, 8, and 13 had one, two, and three or more loci,
      respectively. In 13 tumors with RERs in three or more loci, frameshift mutations
      of TGF-betaRII, insulin-like growth factor II receptor, and BAX were identified
      in 12, 3, and 2, respectively. Compared with GC with none, one or two RER
      positive loci as a group, GC with RERs in three or more loci showed a
      significantly higher frequency of antral location (12 of 13 versus 35 of 67; P =
      0.01), intestinal subtype (11 of 13 versus 30 of 67; P = 0.01), and previous
      Helicobacter pylori infection (12 of 13 versus 41 of 67; P = 0.05) and a lower
      incidence of lymph node metastasis (5 of 13 versus 49 of 67; P = 0.02) and tended
      to be in an advanced stage (12 of 13 versus 54 of 67; P = 0.28). These data
      indicate that GC with multiple RERs manifest distinct clinicopathological
      characteristics, and that a high frequency of frameshift mutations involving the
      TGF-betaRII gene may be causatively linked with tumorigenesis and progression.

PMID- 9537254
TI  - Direct modulation of tumor suppressor connexin 26 gene by human chorionic
      gonadotropin in rat mammary glands.
AB  - Human chorionic gonadotropin (hCG) has been shown to reduce the incidence of
      carcinogen-induced rat mammary tumors. Because connexin 26 (Cx26), a tumor
      suppressor gene candidate, can be up-regulated in mammary epithelial cells during
      lactation, we examined the in vivo and ex vivo effects of hCG on Cx26 expression
      in rat mammary tissues and used its effect on the expressions of beta-casein and
      Cx43 as controls. The Cx26 mRNA and protein expressions were up-regulated by
      daily administrations of 100 units of hCG, starting on day 5 and reaching a 14
      fold maximum increment on days 16 through 21. It remained elevated above the
      basal level even 20 days after hCG withdrawal. The changes in beta-casein
      expression ran parallel to that of Cx26, whereas the expression of Cx43 was down
      regulated. There was no correlation between steroidal hormone levels and Cx26
      expression, except for the first 5 days of hCG treatment. In the ex vivo organ
      culture system, exposure of mammary glands to 10 units/ml hCG for 5 days up
      regulated Cx26 but had no effect on beta-casein expression. These results imply a
      direct induction of the tumor suppressor Cx26 gene by hCG in mammary epithelial
      cells, a mechanism unrelated to lactation.

PMID- 9537255
TI  - Characteristic pattern of chromosomal gains and losses in Merkel cell carcinoma
      detected by comparative genomic hybridization.
AB  - Merkel cell carcinoma or small cell carcinoma of the skin is a rare skin cancer
      seen in increasing numbers in Queensland, Australia. In its clinical course and
      histopathology, it resembles small cell lung carcinoma (SCLC). Little is known of
      the genetic basis of this disease except for a number of cytogenetic studies and
      three loss of heterozygosity studies. Therefore, comparative genomic
      hybridization was performed to determine the characteristic DNA gains and losses
      that occur in this tumor. Comparative genomic hybridization analysis of 34
      specimens from 24 patients revealed a pattern of gains and losses that closely
      resembles that seen in SCLC. Overall frequent loss was seen for chromosomes 3p
      (46%), 5q (21%), 8p (21%), 10 (33%), 11q (17%), 13q (33%), and 17p (25%).
      Significant gains were seen for chromosomes 1 (63%), 3q (33%), 5p (38%), 8q
      (38%), 19 (63%), and X (41%), with smaller numbers having gains for chromosomes
      6, 7, 20, and 21. In contrast to SCLC, amplification in Merkel cell carcinoma is
      a rare event.

PMID- 9537256
TI  - Inhibition of growth of malignant rat prostate tumor cells by restoration of
      fibroblast growth factor receptor 2.
AB  - A loss of expression of fibroblast growth factor (FGF) receptor 2 IIIb
      (FGFR2IIIb), which responds to stroma-derived FGF, accompanies progression of
      premalignant androgen-responsive rat prostate tumor epithelial cells to the
      malignant phenotype. Concurrently, the level of FGFR2 gene expression is reduced
      and lost altogether in over 30% of cells, whereas all malignant cells abnormally
      express FGFR1, which is normally confined to stromal cells (S. Feng et al.,
      Cancer Res., 57:5369-5378, 1997). To determine the relative roles of the FGFR2
      and FGFR1 kinases in growth of malignant cells, we transfected malignant prostate
      epithelial cells with the wild-type FGFR2IIIb kinase and an artificial chimeric
      construct (FGFR2IIIb/R1) composed of the FGFR2IIIb ectodomain and the FGFR1
      kinase domain. Population growth kinetics, in both the absence and presence of
      FGF-7, which binds only the FGFR2IIIb ectodomain, were then examined in the
      transfected cell populations. In contrast to the untransfected malignant tumor
      cells and those expressing the FGFR2IIIb/R1 chimera, FGF-7 caused a dose
      dependent net inhibition of the population growth rates of cells expressing the
      full-length FGFR2IIIb kinase. The results suggest that although the FGFR2 kinase
      can mediate positive mitogenic effects, it mediates a net restriction on the
      growth of prostate tumor epithelial cells relative to FGFR1. Highly malignant
      prostate tumor cells, which have lost the FGFR2 tyrosine kinase, retain the
      cellular response mechanisms to it. Restoration of the FGFR2 kinase to malignant
      tumors that are refractory to treatment may present a new avenue for gene
      therapy.

PMID- 9537257
TI  - Down-regulation of the novel gene melastatin correlates with potential for
      melanoma metastasis.
AB  - We have used differential cDNA display to search for genes whose expression
      correlates with an aggressive phenotype in variants of the B16 murine melanoma
      line, B16-F1 and B16-F10. This analysis identified a novel gene, termed
      melastatin, that is expressed at high levels in poorly metastatic variants of B16
      melanoma and at much reduced levels in highly metastatic B16 variants. Melastatin
      was also found to be differentially expressed in tissue sections of human
      melanocytic neoplasms. Benign nevi express high levels of melastatin, whereas
      primary melanomas showed variable melastatin expression. Melastatin transcripts
      were not detected in melanoma metastases. Within the set of human primary
      cutaneous melanomas examined, melastatin expression appeared to correlate
      inversely with tumor thickness. The expression pattern observed suggests that
      loss of melastatin expression is an indicator of melanoma aggressiveness.

PMID- 9537258
TI  - Comparative decreases in tyrosinase, TRP-1, TRP-2, and Pmel 17/silver antigenic
      proteins from melanotic to amelanotic stages of syngeneic mouse cutaneous
      melanomas and metastases.
AB  - Malignant cutaneous melanomas and metastases were taken directly from in situ
      lesions of genetically identical (C57BL/6 strain) Tyr-SV40E transgenic mice, and
      samples were analyzed by Western immunoblotting with antisera specific for the
      COOH terminus of each of four melanocytic proteins. These were tyrosinase, TRP-1,
      TRP-2, and Pmel 17/silver. Of the 13 melanomas examined, there were 5 melanotic
      primary tumors, 5 amelanotic primary tumors, and 3 amelanotic metastases. The
      melanotic tumors expressed all of the markers to some extent. In contrast, the
      amelanotic tumors lacked detectable levels of one, two, or three of the proteins,
      except for an apparently amelanotic tumor sample in which all were expressed, but
      in which some melanotic cells were likely to have been present. Thus, despite
      some variability, there is clearly a downward trend in the presence of these
      proteins as the tumors become amelanotic, a pigmentary change associated with
      ongoing malignant progression. In the amelanotic tumors, tyrosinase was most
      often deficient, whereas TRP-2 was most often persistently expressed. These
      results, obtained from melanomas of syngeneic origin, indicate that tumors in the
      relatively early stages of malignancy might be more responsive than later-stage
      tumors to immunotherapy involving an ensemble of antigenic peptides of the tested
      gene products. Moreover, TRP-2 peptides may be especially useful for therapeutic
      intervention at the later stages.

PMID- 9537260
TI  - Regulation of interleukin 8 expression in human malignant melanoma cells.
AB  - Here, we report the molecular regulation of interleukin (IL)-8 expression in
      human melanoma cells. The inflammatory cytokines IL-1beta and tumor necrosis
      factor-alpha (TNF-alpha) up-regulated IL-8 expression, in a time- and
      concentration-dependent manner, in three metastatic melanoma variants, SBC-2
      (nonmetastatic), A375P (low metastatic), and A375SM (high metastatic), by
      increased transcription of the IL-8 gene, leading to increased levels of IL-8
      mRNA and protein production. Furthermore, we report that IFN-alpha and IFN-beta
      did not inhibit steady-state IL-8 production. However, IFN-alpha and IFN-beta
      inhibited IL-1beta or TNF-alpha-mediated up-regulation of IL-8 mRNA. In addition,
      IFN-beta demonstrated a more potent inhibitory effect at a lower concentration
      than did IFN-alpha. Both pretreatment and simultaneous treatment of melanoma
      cells with IFN-alpha or IFN-beta inhibited the IL-1beta and TNF-alpha up
      regulation of IL-8 mRNA levels. This inhibition was at the transcriptional levels
      and was unaffected by a protein synthesis inhibitor, suggesting that this did not
      require de novo protein synthesis. Further, modulation of IL-8 levels by IL
      1beta, alone or in combination with IFN-beta, affected the proliferation of
      melanoma cells. In summary, our data suggest that the up-regulation of IL-8
      expression in melanoma cells is regulated at the transcriptional level and is
      rapidly and specifically inhibited by IFN-alpha or IFN-beta, independent of de
      novo protein synthesis, perhaps due to a transient modification of a preexisting
      factor(s).

PMID- 9537259
TI  - Role of nitric oxide and superoxide anion in elimination of low metastatic human
      colorectal carcinomas by unstimulated hepatic sinusoidal endothelial cells.
AB  - Human colorectal carcinoma (CRC) cell survival for the first 24 h after
      implantation in the hepatic sinusoid determines its potential to colonize the
      liver. Nearly 10-fold more highly metastatic CX-1 cells survive within the livers
      of nude mice 24 h after intrasplenic injection than weakly metastatic clone A
      cells. Because CRCs contact sinusoidal endothelial cells (SECs) during
      implantation, we sought to determine whether SECs were more toxic to clone A than
      to CX-1 cells. When 2 x 10(4) vital dye-labeled CRC cells were added to murine
      SEC monolayers, more than 30% of clone A cells lost calcein AM fluorescence
      compared to fewer than 5% of CX-1 cells after 24 h of coculture with SECs.
      Kupffer cells did not mediate this effect, because neither enriched Kupffer cells
      nor SECs treated with a Kupffer cell inhibitor altered the SEC-mediated toxic
      effect to clone A cells. Pretreatment with a nitric oxide synthase inhibitor,
      N(G)-monomethyl-L-arginine, superoxide dismutase, or dexamethasone, blocked SEC
      mediated toxicity to clone A cells, whereas calcium chelation and catalase did
      not. In addition, clone A cells were more sensitive to a superoxide donor, 3
      morpholinosydnonimine N-ethylcarbamide, than were CX-1 cells, and neither cell
      line was sensitive to sodium nitroprusside, a nitric oxide donor. Thus,
      unstimulated murine SECs produce reactive oxygen species that are selectively
      toxic to weakly metastatic clone A cells. This may be a mechanism by which host
      liver cells eliminate weakly metastatic neoplastic cells.

PMID- 9537261
TI  - Overexpressed WAF1/Cip1 renders glioblastoma cells resistant to chemotherapy
      agents 1,3-bis(2-chloroethyl)-1-nitrosourea and cisplatin.
AB  - Previous studies have shown that the negative cell cycle regulator WAF1/Cip1 is
      often overexpressed in human gliomas and that WAF1/Cip1 overexpression may be a
      factor in cancer chemoresistance. We established a doxycycline-inducible
      WAF1/Cip1 expression system in two glioblastoma cell lines and examined the role
      of WAF1/Cip1 in their response to the chemotherapy agents 1,3-bis(2-chloroethyl)
      1-nitrosourea (BCNU) and cis-diamminedichloroplatinum (cisplatin), in an
      isogeneic background. Our results showed that the induction of WAF1/Cip1
      expression rendered glioma cells resistant to cell death induced by BCNU and
      cisplatin. Using an in vivo host-cell reactivation DNA repair assay, we
      demonstrated that WAF1/Cip1 enhances the repair of BCNU-induced DNA damage. We
      conclude that WAF1/Cip1 allows repair of BCNU- and cisplatin-damaged DNA and
      protects glioma cells from chemotherapy agent-induced apoptosis. Thus, blocking
      WAF1/Cip1 production or function may serve as a useful chemosensitization regimen
      for glioma.

PMID- 9537262
TI  - Enhanced expression of alpha(1,3)-fucosyltransferase genes correlates with E
      selectin-mediated adhesion and metastatic potential of human lung adenocarcinoma
      cells.
AB  - Alpha(1,3)- and alpha(1,4)-fucosylated oligosaccharides such as sialyl-Lewis(x)
      (sialyl-Le(x)) and sialyl-Lewis(a) (sialyl-Le(a)) have been reported to
      participate in tumor cell adhesion to activated endothelium. We examined by
      cytofluorometry the expression of Le(x), sialyl-Le(x), sialyl-Le(x) dimeric,
      Le(a), and sialyl-Le(a) on the surface of two human lung adenocarcinoma cell
      lines with different lung colonization potential. High expression levels of all
      of these antigens were detected in the metastatic HAL-8Luc cells, whereas the
      closely related nonmetastatic HAL-24Luc cells only expressed the sialyl-Le(a) and
      sialyl-Le(x) dimeric antigens, both at lower level than in HAL-8Luc cells. Five
      alpha(1,3)-fucosyltransferases (alpha(1,3)-Fuc-T) controlling the synthesis of
      these molecules have been identified to date (Fuc-TIII-Fuc-IVII). The expression
      of these five genes was also higher in the metastatic cells than in the
      nonmetastatic counterparts as was shown by Northern blot analysis. In vitro
      adhesion assays showed that only the metastatic cell line adheres significantly
      to E-selectin-expressing human endothelial cells. Moreover, monoclonal antibody
      (mAb) blockade of E-selectin completely abolished tumor cell binding. Adhesion
      inhibition experiments using mAbs against sialylated fucosylated oligosaccharides
      expressed on tumor cells indicated that these antigens are involved in the
      binding. Anti-sialyl-Lex(x) mAb (CSLEX-1) inhibited adhesion by 85%; it had the
      most pronounced inhibitory effect. These findings suggest that the overexpression
      of alpha(1,3)-Fuc-T genes in the metastatic HAL-8Luc cells, compared with HAL
      24Luc cells, results in an enhanced surface display of fucosylated
      oligosaccharides, which contributes to the adhesive capacity of these cells to
      the activated endothelium and correlates with their lung colonization potential.

PMID- 9537263
TI  - Regulation of expression of thymidine phosphorylase/platelet-derived endothelial
      cell growth factor in human colon carcinoma cells.
AB  - The enzyme/cytokine thymidine phosphorylase/platelet-derived endothelial cell
      growth factor (TP/PD-ECGF) has diverse functions within cells, including the
      regulation of steady-state thymidine levels, the conversion of cancer
      chemotherapeutic agent 5-fluorouracil to an active metabolite, and the mediation
      of angiogenesis in normal and malignant cells. Although the level of TP/PD-ECGF
      expression varies substantially among different individuals, is usually elevated
      in colorectal tumors compared to nonmalignant tissue, and has been shown to be
      directly associated with poor clinical prognosis, little is known about the
      mechanisms for control of TP/PD-ECGF expression. TP/PD-ECGF mRNA levels are
      extremely low in most cell lines in vitro, including HT29 human colon carcinoma
      cells. IFN-alpha and IFN-beta induced an increase in TP/PD-ECGF enzyme activity
      and mRNA levels. The induction of TP/PD-ECGF expression by IFN was not as strong
      as that of another IFN-inducible gene, 2'-5' oligoadenylate synthetase, but in
      contrast to 2'-5' oligoadenylate synthetase, TP/PD-ECGF mRNA levels remained
      elevated for up to 72 h. Experiments suggested that this was due to the
      combination of a rapid but transient increase in the rate of TP/PD-ECGF
      transcription that was accompanied by a more prolonged stabilization of TP/PD
      ECGF mRNA. Using an electrophoretic mobility shift assay, IFN was found to
      rapidly and transiently induce nuclear factors that bound to a putative IFN
      response element in the TP/PD-ECGF promoter. The complex observed was similar but
      not identical to that seen using the consensus IFN-stimulated response element
      sequence as a target. TP/PD-ECGF mRNA also has a pyrimidine-rich sequence at its
      3' end that was similar to a motif that has been reported to mediate increased
      mRNA stability in other genes. These studies indicate that TP/PD-ECGF gene
      expression was subject to regulation by both transcriptional and
      posttranscriptional mechanisms.

PMID- 9537264
TI  - Expression of human telomerase subunits and correlation with telomerase activity
      in cervical cancer.
AB  - Activation of telomerase and stabilization of telomeres are thought to be
      required for both cellular immortality and oncogenesis. Three major components of
      human telomerase, human telomerase RNA (hTR), telomerase-associated protein
      (TP1/TLP1), and human telomerase catalytic subunit (hTRT/hEST2), have been
      identified recently. However, it remains unclear what roles these subunits play
      in the regulation of telomerase activity. In the present study, a total of 25
      cervical cancers and 14 normal cervices as well as various cell lines derived
      from cervical cancer were examined for the expression of hTR, TP1 mRNA, and hTRT
      mRNA, and the correlations between expression of these and telomerase activity
      were evaluated in 23 cancers and 14 normal cervices. Reverse transcription-PCR
      analysis revealed that hTR and TP1 mRNA were commonly expressed in cancers and
      noncancerous tissues. However, hTRT mRNA was observed only in cervical cancers
      and cell lines, and more than 80% of cervical cancers expressed it, whereas
      neither normal cervical tissues nor normal primary fibroblast cells did. There
      was a strong correlation of telomerase activity with hTRT mRNA expression but not
      with TP1 or hTR expression. Cervical exfoliated cells were subjected to reverse
      transcription-PCR analysis for detection of hTRT mRNA, and approximately 70% of
      cervical cancers were positive for such expression. These findings provide strong
      evidence that expression of hTRT is a rate-limiting determinant of the enzymatic
      activity of human telomerase and that up-regulation of hTRT expression may play a
      critical role in human carcinogenesis. Our findings also indicate that detection
      of hTRT mRNA is useful for cytological screening for cervical cancer.

PMID- 9537265
TI  - In vivo electron paramagnetic resonance imaging of tumor heterogeneity and
      oxygenation in a murine model.
AB  - Nitroxides are redox-sensitive probes, which are useful in noninvasively
      delineating tissue heterogeneity especially with respect to metabolic activity
      and tissue oxygenation. Recent studies have shown that nitroxides are in vitro
      and in vivo radioprotectors and selectively protect normal tissue compared to
      tumor tissue. It has been postulated that the basis for selective radioprotection
      of normal tissues is greater bioreduction of nitroxides in tumor tissue compared
      to normal tissue. The aim of the present study was to investigate the
      distribution and lifetime of nitroxides in tumor and normal tissues. Mice were
      implanted with tumor cells (RIF-1) in the thigh, and the tumor was allowed to
      grow to about 10-15 mm in diameter. After i.v. infusion of nitroxides, in vivo
      electron paramagnetic resonance spectroscopy and imaging of the tumor were
      performed using a specially built bridged-loop surface resonator. The
      pharmacokinetic and spatial distribution of the nitroxides in tumor tissue were
      followed and compared with those in normal tissue. Three-dimensional spatial
      images showed significant heterogeneity in the nitroxide distribution as well as
      reduction rates. The nitroxide reduction rates were significantly higher in
      tumors than in the normal tissue. Measurements using spin label oximetry showed a
      substantial difference in the level of oxygenation between normal tissue (muscle)
      and tumor tissue. Average pO2 levels in tumor tissue were found to be 3-fold
      lower than in a corresponding volume of normal tissue. The lower pO2 levels in
      tumor compared to normal tissue may explain the more rapid reduction of
      nitroxides in these tissues. This study demonstrates that electron paramagnetic
      resonance imaging can perform noninvasive anatomical as well as functional
      imaging and provide in vivo physiological information regarding cellular
      metabolism in tumor and normal tissues.

PMID- 9537267
TI  - The next century of tropical health.

PMID- 9537266
TI  - Targeted disruption of the beta1 integrin gene in a lymphoma cell line greatly
      reduces metastatic capacity.
AB  - Integrins have been implicated in tumor metastasis. To investigate this, we
      generated beta1 integrin-negative double knockout (DKO) mutants of the highly
      metastatic ESb murine T-lymphoma cell line. The in vivo growth capacity of the
      mutants, which had lost alpha4beta1 and alpha6beta1 expression, was not altered,
      but their metastatic capacity was greatly reduced. Tail vein injection of 10(4)
      ESb and single-knockout cells led to death of all animals within 9-11 days. In
      contrast, only one-half of the animals injected with 10(4) DKO cells died, but
      much later, after 20-60 days. The other one-half remained disease-free for up to
      100 days. Whereas ESb and single-knockout cells disseminated predominantly to
      liver and spleen, metastasis of DKO cells to these organs was rare, even after
      this prolonged period. Instead, skeletal muscles were invaded extensively.
      Metastatic capacity was largely restored in a DKO clone, which had been
      transfected with beta1 cDNA and expressed beta1 at similar levels as ESb cells.
      We conclude that beta1 integrins are essential for efficient liver and spleen
      colonization by the ESb lymphoma.

PMID- 9537268
TI  - Neuropsychiatric manifestations after mefloquine therapy for Plasmodium
      falciparum malaria: comparing a retrospective and a prospective study.
AB  - Mefloquine has been increasingly used for treatment of chloroquine-resistant
      malaria since its introduction in the late 1970s. In 1987 the first case of toxic
      encephalopathy was published, and in 1989 the WHO initiated reporting and
      investigation of neuropsychiatric adverse reactions of mefloquine.
      Neuropsychiatric adverse drug reactions are now well documented. We compared an
      open prospective 3 year study including all patients with P. falciparum treated
      with mefloquine with an earlier published, retrospective study on a comparable
      population from our department covering the period up to 1989. In the
      retrospective study neuropsychiatric adverse effects were not specifically asked
      for, while in the prospective study possible adverse reactions were registered
      daily according to a specified questionnaire. No case of neuropsychiatric adverse
      reaction was registered in the retrospective study. In the prospective study, 28%
      had one or more neuropsychiatric adverse reactions, although severity was mostly
      mild to moderate. Other adverse reactions occurred in 96% in the retrospective
      study compared to 81% in the prospective study. IN CONCLUSION: one often finds
      only what one looks for, e.g adverse events may be overlooked for a decade, if
      relatively uncommon. This report also shows that retro- and prospective studies
      may give very different results.

PMID- 9537270
TI  - Immunogenicity of Haemophilus influenzae-diphtheria CRM197 protein conjugate
      vaccine (HbOC) in Libyan infants.
AB  - The immunogenicity of the HbOC, a Haemophilus influenzae type b conjugate
      vaccine, was evaluated in a randomized clinical trial of Arab children resident
      in Tripoli. The HbOC vaccine was given as part of a three-dose series at 2, 3 and
      4 months of age together with hepatitis B, OPV and DPT to 90 children. Anti-H.
      influenzae antibody levels were compared with 81 infants receiving hepatitis B,
      OPV and DPT but not the HbOC vaccine. The immunogenicity and safety of HbOC was
      as high as that observed in industrialised countries. There were no major
      complications, and fever and temporary local discomfort were observed in fewer
      than approximately 2% of the infants. Infants receiving the HbOC vaccine had an
      increase in Hib antibodies with only one dose. Geometric mean anti-Hib antibody
      levels were 0.41, 1.36 and 2.91 mg/ml after one, two and three doses. After two
      doses, all children had antibody levels above 0.20 mg/ml and the lowest antibody
      concentration was 0.80 mg/ml. Antibody levels in our children are similar to
      those observed in Europe and the USA and it is thus likely that HbOC will provide
      good clinical protection in this population. As most of the children develop
      antibody titres above or near 1 mg/ml, it is likely that they are protected even
      with two doses of the vaccine. The anti-Hib antibody levels observed are similar
      to those in studies from Europe where hepatitis B vaccine is not routinely given.

PMID- 9537269
TI  - Arabian Peninsula men tend to insulin resistance and cardiovascular risk seen in
      South Asians.
AB  - OBJECTIVE: To test the hypothesis that peninsular Arabs and South Asians share a
      tendency to insulin resistance, differing from other ethnic groups living in the
      United Arab Emirates (UAE). METHODS: A representative sample of 358 apparently
      healthy men aged 35-49 years drawn from a multiethnic office-based workforce in
      the UAE was tested. The sample included a reference group of expatriate South
      Asians, in whom insulin resistance has already been described as the cause of
      high coronary heart disease (CHD) mortality. All subjects were screened for CHD
      risk factors, including glucose tolerance and 2-h serum insulin determinations.
      RESULTS: There was a high prevalence of previously undiagnosed cases of diabetes
      (10.1%) and hypertension (14.2%). South Asian and peninsular Arab men shared the
      tendency to significantly higher 2-h glucose and insulin levels, lower HDL
      cholesterol concentrations and abdominal obesity especially compared to
      Europeans, who were five times less likely to be glucose-intolerant (OR 5.40, P =
      0.015). Three other Arab groups were intermediate in most trends. CONCLUSION:
      Susceptibility to insulin resistance in Arabian peninsula men is strongly
      supported, suggesting that control of obesity and promotion of exercise are the
      best approach to CHD prevention.

PMID- 9537271
TI  - Diagnostic quality in rural health centres in Burkina Faso.
AB  - OBJECTIVE: To study the quality of diagnostic practice in rural Burkina Faso.
      METHOD: In 9 health centres of 3 districts, 313 outpatient consultations were
      observed, and 417 diagnoses by 15 nurses were analysed. Criteria for evaluation
      of patient history and clinical examination were based on the diagnostic
      guidelines distributed by the Ministry of Health. RESULTS: In only 20% of the
      diagnoses the nurses took a sufficient history and in only 40% they conducted a
      sufficient clinical examination. In 21% patients underwent no clinical
      examination at all. Only 12% of all diagnoses were based on sufficient history
      taking and adequate clinical examinations. The individual elements of clinical
      examination were performed correctly in 82% of cases. The variation between
      nurses was immense, but no correlation could be found with regard to their basic
      training. However, nurses who had received the diagnostic guidelines examined
      patients more carefully than those who had not. Larger numbers of patients per
      day are not associated with shorter nurse-patient contact, and neither is
      sufficiency of patient history associated with duration of the consultation.
      CONCLUSION: The low diagnostic quality of the outpatient consultations in the
      studied area indicates that this issue has been neglected in national public
      health initiatives. But examination skills are good and diagnostic guidelines may
      have had a positive effect on the diagnostic quality.

PMID- 9537272
TI  - Direct and indirect costs of the acute form of lymphatic filariasis to households
      in rural areas of Tamil Nadu, south India.
AB  - This study examined the direct and indirect costs due to acute form of lymphatic
      filariasis caused by Wuchereria bancrofti to the households in rural communities
      in Tamil Nadu state in south India. For nearly one-third of the acute
      adenolymphangitis (ADL) episodes the affected did not seek treatment and for 27%
      of the episodes they consulted health personnel, underwent treatment and paid for
      it. On average, the ADL patients spent Rupees (Rs.) 2.35 (US $ 0.07) per episode
      on treatment, but expenditure was as high as Rs. 32.11 (US $ 0.92) among those
      who paid. Doctor's fees and medicines constituted 83% of the total treatment
      costs. Patients with multiple and longer duration episodes and with better living
      conditions spent relatively more on treatment. The proportion of patients who
      spent money on treatment was smaller in poorer households, but their treatment
      costs formed a relatively higher proportion of their income than those of middle
      and high-income households. The ADL episodes curtailed economic and domestic
      activities. In 87% of the episodes, the affected were not able to attend any
      economic activity compared to 37% of the episodes in the case of controls.
      Patients spent only 0.68 +/- 1.91 hours on economic activity compared to 4.40 +/-
      3.74 hours by the control individuals during the ADL episodes. The sign rank test
      showed that the mean difference of 3.73 +/- 3.81 and 2.14 +/- 1.83 hours in the
      time spent on economic and domestic activity respectively between cases and
      controls was highly significant (P < 0.01). Regression analysis demonstrated that
      the difference in the time spent on activities is only due to ADL and no socio
      economic variable had any effect on it. The cost of treatment and loss in
      economic activities combined with high incidence in the study communities
      indicate the extent of the economic burden imposed by the hitherto neglected
      acute form of lymphatic filariasis and the necessity to control it.

PMID- 9537273
TI  - Patterns of antimicrobial use and antimicrobial resistance among healthy children
      in Bolivia.
AB  - OBJECTIVE: To determine the incidence of antimicrobial-resistant, nonpathogenic
      Escherichia coli among healthy children aged 6-72 months in Camiri town and a
      rural village, Javillo, in south-eastern Bolivia. METHOD: A community-based
      survey: stool samples were obtained from 296 healthy children selected by
      modified cluster sampling in Camiri and all 25 eligible children in Javillo. E.
      coli isolates were tested for antimicrobial susceptibility according to the
      standard disc diffusion method. By a questionnaire survey of 12 pharmacies and by
      using simulated patients, we investigated the antimicrobial availability and the
      usage patterns in Camiri town. RESULTS: In Camiri, over 90%, and in Javillo over
      70% of children carried E. coli resistant to ampicillin, trimethoprim
      sulphamethoxazole (TMP/SMX) or tetracycline. Overall, 63% of children carried E.
      coli with multiple resistance to ampicillin, TMP/SMX, tetracycline and
      chloramphenicol. In the simulated patients study, antimicrobials were dispensed
      inappropriately for 92% of adults and 40% of children with watery diarrhoea, and
      were under-prescribed for males with urethral discharge (67%) or females with
      fever and dysuria (58%). The dose and/or duration of antimicrobials dispensed was
      almost always too low. CONCLUSION: Our study showed a disturbingly high
      prevalence of carriage of nonpathogenic E. coli resistant to antimicrobials. The
      prevalence of resistance to ampicillin and TMP/SMX was higher than that
      previously reported in developing countries. The existence of a large reservoir
      of resistance genes in healthy individuals in developing countries represents a
      threat to the success of antimicrobial therapy throughout the world. Programmes
      to improve rational and effective drug use in developing countries are urgently
      needed.

PMID- 9537274
TI  - Cellular immune response of Mastomys and gerbils in experimental filariasis.
AB  - OBJECTIVE: To determine mitogenic and antigen-specific cellular immune responses
      of two species of rodents, viz. Meriones unguiculatus and Mastomys coucha to
      assess the usefulness of the A. viteae/Mastomys model for cellular immune studies
      in experimental filariasis. METHODS: Lymphocyte blast transformation test (LTT)
      using spleen cells of normal and A. viteae infected animals. RESULTS: The
      proliferative response of gerbils was much higher than that of Mastomys to both
      ConA and filarial antigens. Cells of both species of rodents did not respond to
      microfilarial (mf) antigen, however, their mitogenic response differed during
      infection. Some degree of nonspecific suppression was observed in gerbils during
      prepatent and patent stages of infection, while Mastomys revealed highest
      proliferation during patent microfilaraemia. Mastomys cells did not respond to
      adult or mf antigen, while adult-specific proliferation was detected in the case
      of gerbils. CONCLUSION: The A. viteae/gerbil model shows more similarity to human
      filarial infection regarding cellular immune response. Markedly low
      responsiveness of a high percentage of Mastomys and wide variations in the
      cellular response to nonspecific mitogen limit the usefulness of Mastomys coucha
      in immunological studies, especially cellular immunity.

PMID- 9537275
TI  - Retrospective follow-up of maternal deaths and their associated risk factors in a
      rural district of Tanzania.
AB  - OBJECTIVE: To determine the maternal mortality rate in a rural district of
      Tanzania and to measure the incidence of causes of maternal mortality, the
      presence of risk factors and the relationship with social and demographic
      factors. METHOD: From January to December 1993 a retrospective recording of
      maternal deaths was completed using verbal autopsy and networking. RESULTS: A
      total of 76 deaths were found which is equivalent to a maternal mortality ratio
      of 961 per 100,000 live births for this 12-month period of time. The leading
      causes of death were postpartum haemorrhage with retained placenta, anaemia,
      postpartum haemorrhage without retained placenta, AIDS complex and obstructed
      labour (in descending order of frequency). Maternal deaths were seen irrespective
      of group factors such as access to a main road, presence of antenatal risk
      factors and contact with health care personnel or a nearby facility before death.
      Mortality was also present both in home and hospital deliveries (excluding
      hospital referrals). Antenatal care had been received by 97.2% of the mothers who
      died after the second trimester. The referral rate even in the presence of a
      known antenatal risk factor was 34.6%. Patient compliance to the referral was
      only 44.4%. Mothers and their families followed strong cultural beliefs even when
      they were detrimental to the mother's health. Maternal deaths were
      proportionately higher among women > 40 who were also gravid > or = 5, but there
      was no significant increase in deaths in women < 19 years of age. CONCLUSION:
      Effective antenatal care, appropriate emergency treatment of complications,
      access to transportation and competent referral level care with adequate
      equipment encompass the most effective answers to reduction of maternal deaths at
      a district level.

PMID- 9537276
TI  - Pulmonary tuberculosis and health-seeking behaviour: how to get a delayed
      diagnosis in Cali, Colombia.
AB  - Tuberculosis is a heavy burden in the developing countries. Early diagnosis and
      adherence to treatment are difficult to achieve by patients. Our qualitative
      research looked at the paths followed and the barriers experienced by patients at
      the health care services of Cali, Colombia, while seeking help for pulmonary
      tuberculosis symptoms. Results show that the cultural-based explanation patients
      give to the symptoms, the stigma attached to the disease, and the poor quality of
      health care services (communication skills, organizational structure, attitudes,
      and knowledge of the tuberculosis control strategy of health care workers) are
      strong barriers to early diagnosis.

PMID- 9537277
TI  - The cost of treating paediatric malaria admissions and the potential impact of
      insecticide-treated mosquito nets on hospital expenditure.
AB  - OBJECTIVE: To calculate the costs at Kilifi District Hospital (KDH) and Malindi
      Sub-district Hospital (MSH) of treating paediatric malaria admissions including
      three common presentations of severe paediatric malaria, i.e. cerebral malaria,
      severe malaria anaemia and malaria-associated seizures; and to estimate the
      implications for hospital expenditure of a reduction in paediatric malaria
      admissions. METHODS: Patient data were obtained from hospital records. All costs
      were allocated to departments that provided direct patient care by a four-stage
      step-down procedure. Laboratory and drug costs of treating paediatric malaria
      admissions were separately identified. RESULT: Unit recurrent costs per admission
      in KDH ranged from US $57 for 'other' paediatric malaria to US $105 for cerebral
      malaria, and in MSH from US $33 to US $44 for the same categories. The annual
      recurrent cost of treating all paediatric malaria admissions to KDH prior to the
      trial was estimated at US $78 900. Adjusting for preintervention differences in
      malaria admission rates and age between intervention and control areas, the ITBN
      trial found a 41% reduction in paediatric malaria admissions. The reduction in
      admissions resulted in an estimated saving of US $6240 in the cost of treating
      paediatric malaria admissions from the intervention area. CONCLUSION: There would
      be a substantial reduction in costs of treating paediatric malaria admissions if
      the intervention were introduced in the whole catchment area of the hospital.
      Actual savings would depend on the proportion of potential savings that can in
      practice be realised, and on the effectiveness of the intervention when routinely
      implemented.

PMID- 9537279
TI  - Exchange transfusion as an adjunct to the treatment of severe falciparum malaria.
AB  - OBJECTIVE: To compare the efficacy of exchange transfusion as the adjunct to
      quinine treatment (21 patients) with quinine therapy alone (29 patients). METHOD:
      A retrospective study of 50 patients with severe falciparum malaria was conducted
      at Chumphorn Hospital, Southern Thailand. RESULTS: Clinical characteristics in
      both treatment groups were not significantly different although in the exchange
      transfusion group, the admission geometric mean parasitaemia (18 (5%), and the
      proportion of patients with more than 10% parasitaemia was higher (76%, P = 0.03)
      than in the group who received quinine alone (10 +/- 4%; 38%, P = 0.1). The
      mortality rate of patients who received exchange transfusion was 48%; that of the
      remainder, 69%. (P = 0.3). ARDS (P = 0.01) and oliguric renal failure (P = 0.04)
      were significant risk factors for death in these patients. CONCLUSION: Exchange
      transfusion was safe and well tolerated. Results of our study revealed a 20%
      reduction in mortality when exchange transfusion was used as an adjunct to
      quinine treatment. It should therefore be considered in patients with severe
      falciparum malaria when possible.

PMID- 9537278
TI  - Utility of antibodies against a 22 kD molecule of Dirofilaria immitis in the
      diagnosis of human pulmonary dirofilariasis.
AB  - To assess the characteristics of an ELISA test for the diagnosis of human
      pulmonary dirofilariasis, we studied the sera of 24 subjects with other
      helmintoses and of 37 patients suffering from non-parasitic focal lung diseases,
      comparing them with negative and positive sera. ELISA and Western blot with
      complete somatic antigen and ELISA with protein Di22 (specifically recognized in
      cases of lung dirofilariasis) were performed. With ELISA SA the false positive
      rate was 25% in cases with other parasitoses and 30% in cases with focal lung
      diseases. ELISA Di22 decreases this positivity levels. Only 2 cases with visceral
      larva migrans (8.3%) and a case with lung nodules metastatic from renal
      adenocarcinoma (2.7%) were positive. ELISA Di22 therefore greatly decreases the
      false positive rate of ELISA SA.

PMID- 9537280
TI  - Differences in the extent of inflammation caused by intratracheal exposure to
      three ultrafine metals: role of free radicals.
AB  - Nickel and cobalt, which belong to the same elemental group, are known to cause
      interstitial lung disease and bronchial asthma. The ability of these metals to
      injure lung cells and cause inflammation is likely to be important in their
      pathogenicity but comparative studies are rare. Additionally, ultrafine (uf)
      forms of these metals are used increasingly and there is little available
      information on their toxicity. Thus the inflammatory response following
      intratracheal instillation of ultrafine particles of Co, Ni, and TiO2 was
      compared. Physiological saline (PS) was used as a vehicle control and DQ12 quartz
      as a positive control. Male Wistar rats were intratracheally instilled with the 3
      particle types at a dose of 1 mg suspended in physiological saline. At 1, 3, 7,
      15, and 30 d after the injection, lung weight and the cellular and biochemical
      changes in bronchoalveolar lavage fluid (BALF) were determined. By all of the
      indices, Uf-Ni appeared to be the most injurious to the lung, causing severe and
      sustained inflammation, cytotoxicity and increased epithelial permeability. The
      next most toxic material was DQ12 quartz, with Uf-Co being closely similar in
      ability to cause inflammation. Uf-TiO2 was more active than the saline control in
      all of the indices, but was the least toxic of the particles studied. The present
      study reveals that three ultrafine particles of the same diameter are
      dramatically different in their ability to cause inflammation. The three
      ultrafines were compared as to their ability to cause free-radical damage to
      supercoiled plasmid DNA, and the result of free-radical activity was found to be
      Uf-TiO2 << Uf-Co = Uf-Ni. Difference in free-radical-generation activity
      therefore could underlie the difference in inflammation of these three ultrafine
      particle types.

PMID- 9537281
TI  - Expression of Hras-p21 and keratin K13 in UVR-induced skin tumors in Sencar mice.
AB  - An ultraviolet radiation (UVR)-induced Sencar mouse skin carcinogenesis model was
      established to investigate the expression of Hras-p21 and keratin K13 in
      different stages of carcinogenesis, including UV-exposed nontumor skin,
      papillomas, squamous-cell carcinomas (SCCs), and malignant spindle-cell tumors
      (SCTs). Expression of Hras-p21 and K13 was examined in paraffin-embedded tumor
      sections by using immunohistochemical, immunofluorescent, and double staining
      techniques with specific antibodies. Positive Hras-p21 staining was detected in
      1/3 (33%) papillomas, 24/36 (67%) of SCCs, but not in UVR-exposed nontumor skin
      or SCTs. Positive staining of the malignant progression marker K13 was found in
      22/36 (61%) of SCCs only. Coexpression of Hras-p21 and K13 was found in
      17/36(47%) SCCs. H-ras exons 1 and 2 were amplified from skin/tumor sections by
      using nested polymerase chain reaction (PCR). PCR-based single-strand
      conformation polymorphism (SSCP) analysis and gene sequencing revealed three
      point mutations, one in UVR-exposed nontumor skin (codon 56), and two in SCCs
      (codons 13 and 21). There were no clear relationships between point mutations of
      H-ras and the positive staining of Hras-p21 and K13. These results indicate that
      overexpression of ras-p21 in conjunction with aberrant expression of K13 is a
      frequent event in UVR-induced SCCs in Sencar mouse skin. Point mutation of the H
      ras gene appeared to be a rare event in UVR skin carcinogenesis and not to be
      responsible for overexpression of Hras-p21.

PMID- 9537282
TI  - Comparative pharmacodynamics of CYP2B induction by DDT, DDE, and DDD in male rat
      liver and cultured rat hepatocytes.
AB  - In this study the pharmacodynamics were characterized of rat hepatic cytochrome P
      450 2B (CYP2B) induction by the pesticide DDT [1,1,1-trichloro-2,2-bis(p
      chlorophenyl)ethane] and its metabolites DDE [1,1-dichloro-2,2-bis(p
      chlorophenyl)ethylene], which is bioretained, and DDD [1,1-dichloro-2,2-bis(p
      chlorophenyl)ethane], which is metabolized further and therefore less prone to
      bioaccumulate. DDT, DDE, and DDD were each found to be pure phenobarbital-type
      cytochrome P-450 inducers in the male F344/NCr rat, causing induction of hepatic
      CYP2B and CYP3A, but not CYP1A. The ED50 values for CYP2B induction
      (benzyloxyresorufin O-dealkylation) by DDT, DDE, and DDD were, respectively, 103,
      88, and > or = 620 ppm in diet (14 d of exposure). The efficacies (Emax values)
      for induction of benzyloxyresorufin O-dealkylation by DDT, DDE, and DDD were 24-,
      22-, and > or = 1-fold, respectively, compared to control values. The potencies
      of the three congeners for CYP2B induction appeared also to be similar, with EC50
      values (based on total serum DDT equivalents) of 1.5, 1.8, and > or = 0.51
      microM, respectively. The EC50 values based on DDT equivalents in hepatic tissue
      were 15, 16, and > or = 5.9 micromol/kg liver tissue, respectively. In primary
      cultures of adult rat hepatocytes, DDT, DDE, and DDD each displayed ability to
      induce total cellular RNA coding for CYP2B (ED50 values of 0.98, 0.83, and > or =
      2.7 microM, respectively). These results suggest that DDT, DDE, and DDD each
      possess a high degree of intrinsic CYP2B-inducing ability for rat liver, despite
      marked differences in bioretention among the congeners.

PMID- 9537283
TI  - Vitamin E modulation of dieldrin-induced hepatic focal lesion growth in mice.
AB  - The effect of vitamin E on dieldrin-induced hepatic focal lesion growth in male
      B6C3F1 mice previously treated with diethylnitrosamine (DEN) was investigated.
      After hepatic focal lesions were formed, mice were placed into one of the
      following treatment groups: Group 1, 50 mg vitamin E/kg diet (control NIH-07
      diet); Group 2, 10 mg dieldrin/kg NIH-07 diet; Group 3, 10 mg dieldrin and 450 mg
      vitamin E/kg NIH-07 diet; and Group 4, 450 mg vitamin E/kg NIH-07 diet. Mice were
      killed and necropsied after 30 and 60 d of dietary treatment. The effect of
      treatment on lesion growth was examined by measuring the number of focal lesions
      per liver and the relative hepatic focal lesion volume. In addition, the possible
      cellular mechanism of focal hepatocyte growth was investigated by examining both
      focal DNA synthesis and apoptosis. Dieldrin treatment alone (Group 2) increased
      the focal lesion volume, focal lesion number, and focal lesion labeling index.
      Supplementation with vitamin E (Group 3) blocked this effect. Vitamin E
      supplementation to the diet alone (Group 4) also enhanced focal lesion growth and
      increased the number of lesions per liver, the relative focal volume, and the
      labeling index in hepatic focal lesions. Interestingly, vitamin E supplementation
      inhibited apoptosis in normal liver but did not produce an observable decrease in
      apoptosis in hepatic focal lesions. The present study showed that dieldrin (Group
      2) or vitamin E supplementation alone (Group 4) promoted the growth of hepatic
      focal lesions in mice. However, when vitamin E is supplemented to dieldrin-fed
      mice (Group 3), there is an inhibition of hepatic focal lesion growth.

PMID- 9537284
TI  - Effect of glucan on murine lungs.
AB  - Glucan, a folded high-molecular-weight polysaccharide, has multiple effects in
      animals when administered intravenously or intraperitoneally, but not when
      administered by inhalation. The hypotheses tested were whether intratracheal
      administration of glucan can cause lung damage and whether some of the resulting
      lung injury is immunologically mediated. There was a dose-response relationship
      between the amount of intratracheally injected glucan and the extent of pulmonary
      histologic abnormalities, which consisted of peribronchiolar and intraalveolar
      infiltration with chronic inflammatory cells. An attempt to adoptively transfer
      increased susceptibility to glucan induced lung injury was made. Cells cultured
      with glucan were transferred into naive recipients before intratracheal glucan
      exposure. The extent of pulmonary inflammation that occurred as a result of
      intratracheal injection of glucan was not affected by transfer of cultured cells
      from glucan-treated animals. However, high concentrations of glucan in culture
      did produce cells with the appearance of lymphoblasts. These data indicate that
      glucan induces lung injury, but that there is no evidence of cell mediation of
      pulmonary injury induced by intratracheal exposure to glucan.

PMID- 9537285
TI  - The autonomic innervation of the epididymis: its effects on epididymal function
      and fertility.

PMID- 9537286
TI  - Environmental hormones and the male reproductive system.

PMID- 9537287
TI  - Cytoplasmic extrusion and the switch from creatine kinase B to M isoform are
      completed by the commencement of epididymal transport in human and stallion
      spermatozoa.
AB  - Although in several species there is a relationship between epididymal sperm
      transport and fertility, in human in vitro fertilization (IVF), spermatozoa
      recovered from the caput epididymidis or even the rete testis are fertile. We
      studied two objective markers of sperm maturity in the sperm of men and
      stallions: creatine kinase (CK) concentrations, which are a measure of
      cytoplasmic retention in immature spermatozoa, and the ratio of CK-M and CK-B
      isoforms (% CK-M/[CK-M + CK-B]), which is proportional to the incidence of mature
      sperm. The CK markers and the fertilizing function are closely related: Immature
      sperm with cytoplasmic retention do not bind to the zona, because during
      cytoplasmic extrusion, the sperm plasma membrane is also remodeled. We examined
      whether changes in sperm CK values are still ongoing during epididymal transport,
      or if cellular maturation is completed prior to the arrival of sperm in the caput
      epididymidis. The incidences of mature sperm in human caput and corpus
      epididymidis (studied in six men with obstructive azoospermia of various
      pathogeneses) were (mean+/-SEM) 55.7+/-2.2 and 49.3+/-7.6%, respectively; and the
      sperm CK-M ratios in the caput epididymidis of three men were 72, 75, and 70%,
      values that are similar to those of ejaculated sperm. In four segments of the
      proximal and distal epididymis of three stallions (the origin of sperm was also
      verified by the position of the cytoplasmic droplet) and in ejaculate of five
      stallions, the incidences of mature sperm were 88.2+/-6.2, 89.0+/-6.7, 90.3+/
      7.8, 87.6+/-5.9, and 86.7+/-0.8%, and the respective CK-M ratios were 75.0+/-8.7,
      84.2+/-2.9, 87.9+/-1.2, 92.5+/-1.5, and 69.3+/-3.5%. There were no differences in
      the incidences of mature and immature spermatozoa or in CK-M ratios among sperm
      arising from the various epididymal regions or from the ejaculate in men or
      stallions. Thus, the cellular maturation events in sperm, as detected by the CK
      markers, are completed by the time the sperm commences epididymal transport.
      These findings are in agreement with the IVF fertility of sperm aspirated from
      the male reproductive tract. The data may also suggest that the primary role of
      sperm epididymal transport in men is to remodel the plasma membrane to enhance
      sperm functional integrity in the diverse environments of the male and female
      reproductive tracts prior to fertilization.

PMID- 9537289
TI  - Catalase and oviductal fluid reverse the decreased motility of bovine sperm in
      culture medium containing specific amino acids.
AB  - The motility and velocity of bovine spermatozoa incubated in TCM-199 are reduced
      in comparison with those incubated in a simpler media made for sperm, such as
      modified Tyrode (Sp-Talp). Moreover, a previous study showed that oviductal cells
      conditioned media prevented this decreased motility in TCM-199. Preliminary
      results lead us to suspect that amino acids in TCM-199 were involved in the
      reduced survival. Therefore, the current experiment aimed at determining which
      amino acids were involved and what their mechanism of action involved. Amino
      acids were added separately in Sp-Talp at the final concentration found in TCM
      199. Frozen-thawed bovine spermatozoa were washed twice by centrifugation in Sp
      Talp and diluted to 25 x 10(6)/ml in the amino acid media. After 6 hours of
      incubation at 37 degrees C, sperm motility and velocity were recorded. The
      percentage of motile sperm was significantly lower in the presence of
      phenylalanine (6%+/-2, P < 0.05) compared with the control (46%+/-2). Sperm
      velocity (VAP, microm/ second) was lower in the presence of phenylalanine (50+/
      4) and tyrosine (89+/-3) compared with the control (119+/-4, P < 0.05). Increased
      concentrations of the three aromatic amino acids (0, 0.2, 1, five times TCM-199
      concentrations) decreased both sperm motility and velocity in a dose-dependent
      manner. Cysteine and methionine, added at 250 microg/ml, showed a negative effect
      on sperm motility and/or velocity, as did the three aromatic amino acids.
      Presence of catalase (0.01 mg/ml) in the amino acid-supplemented Sp-Talp for 6
      hours kept sperm motility and velocity at control levels, suggesting that the
      toxic effect of amino acids acts on sperm by excess hydrogen peroxide production.
      Because the oviduct contains amino acids, and its role as a reservoir for sperm
      survival is well known, oviductal fluid was collected and tested. Oviductal fluid
      reversed the negative effect of amino acids, similar to the action of the
      catalase. Oviductal fluid also kept the peroxide concentrations of media
      containing phenylalanine at basal levels (<10 microM) compared with phenylalanine
      alone (approximately 40 microM). These results suggest the presence of catalase
      activity in oviductal fluid.

PMID- 9537288
TI  - Androgen regulation of the Pem homeodomain gene in mice and rat Sertoli and
      epididymal cells.
AB  - Although the role of homeodomain transcription factors during embryogenesis is
      well known, their developmental function in postnatal animals is only beginning
      to be understood. We examined the regulation and expression pattern of Pem, a
      homeodomain protein that may regulate androgen-dependent events in the testis and
      epididymis. Immunohistochemical analysis showed that Pem protein is expressed
      selectively in the nuclei of Sertoli cells during the androgen-dependent stage of
      the seminiferous epithelium cycle in vivo. RNase protection analysis revealed
      that a proximal promoter was responsible for androgen-dependent mouse Pem
      expression in testis and epididymis in vivo, whereas a distal promoter was used
      in placenta. The mouse Pem gene was expressed at approximately 10-fold higher
      levels in the testis than in the epididymis; conversely, the rat Pem gene was
      expressed at >10-fold higher levels in the epididymis than in the testis. Because
      androgen-binding protein has been proposed to transport androgens from the testis
      to the epididymis, we tested whether the > or = 20-fold higher levels of androgen
      binding protein expression in the rat, compared to that of mouse, are responsible
      for the differential expression of Pem in these two rodent species. Studies with
      androgen-binding protein transgenic mice demonstrated that the species-specific
      difference in androgen-binding protein expression is unlikely to be responsible
      for the species-specific difference in Pem expression. We found that androgen is
      necessary but not sufficient for Pem expression, since purified Sertoli cells
      rapidly down-regulated Pem transcripts in culture, regardless of the presence of
      testosterone. We conclude that Pem gene expression in Sertoli cells requires
      other cell types or cellular factors in addition to androgen.

PMID- 9537290
TI  - Characterization of cysteamine as a potential contraceptive anti-HIV agent.
AB  - Cysteamine (beta-mercaptoethylamine, or MEA) is a thiol-reducing agent and has
      anti-HIV activity. Because of these properties, cysteamine was evaluated as a
      vaginal contraceptive and tested for its effects on sperm function and on other
      sexually transmitted microbes. Cysteamine was contraceptive in the rabbit.
      Conception was inhibited completely when sperm were pretreated with 500 microg/ml
      cysteamine and was inhibited by more than 60% when 7.5 mg cysteamine was applied
      vaginally as a suspension in 50% K-Y Jelly. Cysteamine had multiple effects on
      spermatozoa. Both acrosin (EC 3.4.21.10) and hyaluronidase (EC 3.2.1.35) were
      reversibly inhibited by cysteamine. Calculated IC50 values were 370 microg/ml and
      150 microg/ml for acrosin and hyaluronidase, respectively. Cysteamine behaved as
      a poor spermicide when activity was measured by the 30-second Sander-Cramer test.
      However, sperm motility was inhibited completely when cysteamine was preincubated
      for 10 minutes prior to motility evaluation, at concentrations as low as 50
      microg/ml. The calcium ionophore A23187-induced human acrosome reaction was
      inhibited by cysteamine (IC50 = 0.5 microg/ml). Neither herpes simplex virus nor
      Neisseria gonorrhoeae was affected by cysteamine at concentrations as high as 500
      microg/ml and 100 microg/ml, respectively. Cysteamine appears to have no effect
      on normal vaginal flora (i.e., lactobacillus). These results, together with
      published data, strongly support the further development of cysteamine as a
      topical contraceptive anti-HIV agent.

PMID- 9537291
TI  - Transforming growth factor-beta1 (TGF-beta1) in penile and prostate growth in the
      rat during sexual maturation.
AB  - The goal of this study was to determine whether transforming growth factor-beta1
      (TGF-beta1) may contribute to the arrest of penile growth and the down-regulation
      of androgen receptors (AR) that occur during sexual maturation in the rat penis.
      For this purpose, body, penis, and prostate weights were obtained from male rats
      of increasing ages, and penis and prostate TGF-beta1 concentrations were
      determined by a sandwich enzyme-linked immunosorbent assay. The cytosol fraction
      was obtained from the shafts and glandes of immature (19-day-old) and adult (90
      day-old) rat penises, and ARs were measured by a western blot assay. The effect
      of exogenous TGF-beta1 on penile growth was examined in vivo in two groups of
      immature rats (21 and 27 days old) implanted with miniosmotic pumps delivering
      either human TGF-beta1 or vehicle only directly into the corpora cavernosa for 6
      days. The penises, prostates, and testes were weighed, and the AR content was
      estimated by western blot. The growth rate of the penis declined after 8 weeks of
      age, whereas the ventral prostate growth rate increased until 14 weeks of age and
      then slowed down. The content of penile AR protein decreased seven-fold in the
      adult rats compared to the immature animals. Penile TGF-beta1 concentration
      increased nearly three-fold from the 19-day-old rats to a peak at 60 days of age
      and then decreased over the next 4 months to the initial levels. In contrast, TGF
      beta1 concentration in the prostate was not significantly affected by age and
      remained below the lowest penile values in all age groups. Transforming growth
      factor-beta1 given locally to the penis reduced penile shaft weight by 38 and 22%
      in two groups of immature rats, while the weights of the penile glans, testis,
      and ventral prostate remained unaffected. Androgen receptor content was higher in
      the glans than in the shaft and was not changed by TGF-beta1 treatment. These
      results suggest that the increase of TGF-beta1 levels in the penis may reinforce
      growth arrest caused by the down-regulation of penile ARs, whereas the
      maintenance of a high content of ARs and a low TGF-beta1 concentration may allow
      prostate growth to continue.

PMID- 9537292
TI  - Evidence for nitric oxide regulation of hamster sperm hyperactivation.
AB  - Involvement of reactive oxygen species has been implicated in the process of
      hyperactivation and capacitation of sperm. Nitric oxide has recently been found
      to function both as an intracellular and extracellular messenger, with its
      synthetic enzyme found in several cell types, including male and female genital
      tract organs. The objective of the present study was to investigate the role of
      nitric oxide in hamster sperm hyperactivation. Caudal epididymal contents of
      mature golden hamster sperm were diluted with human tubal medium supplemented
      with a sperm motility preparation. Inhibitors of nitric oxide synthase (nitro-L
      arginine, methyl-L-arginine, and 1,3-phenylene-bis[1,2-ethenediyl]-bis
      isothiourea) were added to incubation media in various doses. Alternatively, a
      nitric oxide donor, sodium nitroprusside, was used. The percentage motile and
      grade of movement were recorded at intervals encompassing the normal period of
      capacitation and hyperactivation. Acrosomal status was evaluated by phase
      contrast microscopy. Inhibition of nitric oxide synthesis did not affect motility
      during early capacitation but dramatically inhibited later hyperactivation. An
      inactive stereo-enantomere of the inhibiting drug had no effect. Addition of
      nitric oxide to nonstimulated sperm induced hyperactivation in a similar time
      course. In conclusion, nitric oxide plays a significant role in hyperactivation
      of hamster epididymal sperm.

PMID- 9537293
TI  - Rat testicular germ cells and epididymal sperm contain active P450 aromatase.
AB  - Although testosterone is the principal sex steroid produced by the testis,
      estrogen is known to be produced by both Leydig and Sertoli cells during
      different developmental periods. Additionally, evidence is unfolding to suggest
      that germ cells might also participate in the synthesis of estrogen within the
      male reproductive tract. We have recently reported that the messenger ribonucleic
      acid (mRNA) for P450 aromatase (P450arom), the enzyme that converts androgen to
      estrogen, is synthesized by rat germ cells. Therefore, the present study was
      conducted to determine which germ cell types synthesize active P450arom and to
      measure the activity of this enzyme in germ cells throughout spermatogenesis and
      in maturing sperm during epididymal transit. First, P450arom activity was
      measured in pachytene spermatocytes, round spermatids, and a mixture of round
      spermatids, elongating spermatids, and residual bodies using the tritiated water
      (3H2O) assay. Second, sperm isolated from different regions of the epididymis
      were assayed for P450arom activity. Sperm isolated from the caput epididymis with
      attached efferent ductules had the higher P450arom activity, whereas sperm
      isolated from the corpus and cauda epididymides had lower P450arom activity. The
      decrease in P450arom activity in cauda sperm was further confirmed by
      immunocytochemistry. On the basis of these observations, we conclude that rat
      testicular germ cells from pachytene spermatocytes through elongating spermatids
      and epididymal sperm contain active P450arom and that sperm lose aromatase
      activity as they mature during epididymal transit. Therefore, both post-pachytene
      rat germ cells and epididymal sperm are capable of estrogen synthesis and are an
      additional, potentially significant, source of estrogen in the male reproductive
      tract.

PMID- 9537294
TI  - Suppression and recovery of spermatogenesis following spinal cord injury in the
      rat.
AB  - Recently, we reported that changes in spermatogenesis in adult rats during acute
      phase (within 2 weeks) of spinal cord injury (SCI) were associated with a
      suppression of pituitary-testis hormone axis, and these effects mimic those that
      occur after hormone deprivation. In this study, we examined the long-term (>4
      weeks) effects of SCI on spermatogenesis and its recovery. Results of this study
      reveal that while serum follicle stimulating hormone, luteinizing hormone, and
      testosterone levels in SCI rats recovered within 1 month after the injury, their
      spermatogenesis continued to regress. By 3 months, spermatogenesis in 70% of SCI
      rats has totally regressed, characterized by the absence of proliferating
      spermatogonia; these effects could not be prevented by an otherwise effective
      regimen of testosterone treatment. Sertoli cells in the regressed seminiferous
      tubules exhibited unusual behavior, characterized by the formation of multiple
      cell layers and/or aggregates that extended into the tubular lumen. Active
      spermatogenesis was observed in nine of the 19 SCI rats by 6 months, seven of
      which had complete spermatogenesis, but with persisting abnormalities. These
      results demonstrate that SCI results in total, but reversible, regression of
      spermatogenesis. Failure to prevent such effects by an otherwise effective
      exogenous testosterone regimen suggests that non-endocrine factors are involved
      in the SCI effects on spermatogenesis. The unusual Sertoli cell localization in
      the regressed testes may have been triggered by the loss of proliferating
      spermatogonia and may be involved in subsequent spermatogenic recovery.

PMID- 9537295
TI  - Analysis of promoter and androgen regulatory sequences required for optimal
      transcription of the rat androgen-binding protein gene.
AB  - The androgen-binding protein (ABP) gene P1 promoter directs cell-specific gene
      regulation of ABP secreted by Sertoli cells. A recent study using the mouse
      Sertoli cell line (MSC-1) with a luciferase reporter system demonstrated Sertoli
      cell-specific gene expression with 619 bp of P1 DNA. Furthermore, based on
      studies of the rat and human genes, several controversies developed over the
      promoter characteristics, including the promoter type, the transcription start
      site, and whether the gene is regulated directly by androgens. In this study, the
      answers to several of these controversies were deciphered using the MSC-1 cell
      model. The results of mutagenesis experiments were consistent with the presence
      of the major transcription start site at 36 bp upstream of the initiating Met
      residue. Modification of the initiator sequence at the start site reduced
      activity in MSC-1 and NIH3T3 fibroblast cells. Mutation of a putative modified
      TATA sequence or conversion to the consensus TATA sequence had no effect on
      activity. Modification of a consensus RNA splice sequence at the start site also
      had no effect on activity. Furthermore, a minor start site was localized 179 bp
      upstream of the major site using reverse transcriptase-polymerase chain reaction
      with various P1 primers (primer walking), primer extension, and cDNA cloning. RNA
      transcripts from the minor site contain an untranslated 5' exon but apparently
      encode the same protein as the major transcript. The effect of androgens on P1
      expression was also investigated. Cotransfection experiments with pCMVAR, which
      encodes the androgen receptor, demonstrated that dihydrotestosterone had no
      effect on the activity in MSC-1 cells. Taken together, these experiments and
      previous studies indicate that the rat ABP promoter P1 is regulated at the major
      start site by an initiator element without a TATA sequence, and the gene appears
      not to be directly regulated by follicle-stimulating hormone or androgens.

PMID- 9537296
TI  - Oxidative stress differentially regulates the expression of gamma-glutamyl
      transpeptidase mRNAs in the initial segment of the rat epididymis.
AB  - Reactive oxygen species (ROS) have a powerful cytotoxic effect on spermatozoa and
      have been implicated in spermatozoal dysfunction and male infertility. gamma
      Glutamyl transpeptidase (GGT) is essential to the metabolism of the antioxidant
      glutathione and, as such, is believed to be important in protecting spermatozoa
      against oxidative stress. The aims of this study were 1) to establish in vitro
      conditions in which ROS were generated and 2) to determine whether oxidative
      stress regulated the expression of GGT mRNAs I-IV in the initial segment of the
      epididymis. Initial segments were collected from adult male rats and incubated in
      culture media to which ROS-generating compounds, hypoxanthine and xanthine
      oxidase, were added. By 6.5 hours, incubation of tissue in high-oxidative stress
      conditions caused a 56% decrease in reduced glutathione concentration, a
      concomitant 240% increase in oxidized glutathione concentration, and a 25%
      decrease in adenosine triphosphate concentration. RNase protection analyses
      demonstrated an approximate 70% up-regulation of GGT mRNAs II-IV in a
      differential manner, depending on the concentration of oxidizing agents and the
      type of ROS generated. gamma-Glutamyl transpeptidase mRNA I was not expressed.
      These results support the hypothesis that expression of GGT mRNAs is regulated by
      oxidative stress in the initial segment of the rat epididymis.

PMID- 9537297
TI  - Gonadal and pituitary responsiveness of stallions is not down-regulated by
      prolonged pulsatile administration of GnRH.
AB  - The objective of this study was to determine if prolonged pulsatile
      administration of homologous gonadotropin-releasing hormone (GnRH) at therapeutic
      or 5x therapeutic doses would cause down-regulation of the stallion's
      hypothalamic-pituitary-testicular axis. Fifteen stallions were randomly assigned
      to three treatment groups (n=5/group) and received a 0.5 ml subcutaneous dose of
      saline (group 1), 50 microg GnRH (group 2), or 250 microg GnRH (group 3) every 2
      hours for 75 days. Weekly evaluations of follicle stimulating hormone,
      luteinizing hormone, and testosterone and monthly evaluations of daily sperm
      output and spermatozoal motility failed to demonstrate any decreased pituitary or
      gonadal responsiveness within or among treatment groups (P > 0.1) as a result of
      treatment with GnRH. Results of this study demonstrate that the hypothalamic
      pituitary-testicularaxis of the stallion, unlike that of other domestic species,
      is remarkably refractory to GnRH-induced down-regulation.

PMID- 9537298
TI  - Dogfish shark (Squalus acanthias) testes contain a relaxin.
AB  - Relaxin is a 6-kd polypeptide that exerts important hormonal effects in many
      female mammals. Relaxin is produced by the ovary, placenta, or uterus in many
      mammalian species. The functions of relaxin in the male mammal are not yet firmly
      established, but there is some evidence suggesting an exocrine effect on sperm
      motility and fertilizability. In the male mammals that have been studied, relaxin
      is produced by the prostate gland (human) or seminal vesicles (boar). However, in
      the bird, the testis is the likely source of relaxin. Among the elasmobranchs,
      ovaries obtained from dogfish sharks have been shown to contain a polypeptide
      hormone that is structurally, biologically, and immunologically similar to
      mammalian relaxins, but the male reproductive tract of this species has not
      previously been investigated as a potential source of relaxin. Extracts of testes
      obtained from mature dogfish sharks have now been tested by a specific relaxin
      bioassay and by a homologous porcine radioimmunoassay for the presence of
      relaxin. Both crude and partially purified testicular extracts contained
      unmistakable guinea pig pubic symphysis-"relaxing" activity and relaxin-like
      immunoactivity. Following immunoaffinity purification, the shark testis
      polypeptide had an apparent specific activity of 88 microg porcine relaxin
      equivalents per milligram in the radioimmunoassay, which is similar to the
      immunoactivity of pure shark ovarian hormones. These data, therefore, strongly
      support the view that in dogfish sharks, the male as well as the female gonad
      produces relaxin. Furthermore, as the dogfish shark has existed as a species for
      about 200 million years, the data suggest that testicular relaxin appeared early
      in vertebrate evolution.

PMID- 9537299
TI  - Micronutrients and HIV infection: a review.

PMID- 9537300
TI  - Lipid content and essential fatty acid (EFA) composition of mature Congolese
      breast milk are influenced by mothers' nutritional status: impact on infants' EFA
      supply.
AB  - OBJECTIVE: To measure the lipid content and the fatty acid (FA) composition of
      breast milk as part of a nutritional survey of the essential fatty acid (EFA)
      status of 5 months old Congolese infants. DESIGN: Cross sectional nutrition
      survey. SETTING: A suburban district of Brazzaville (capital of the Congo).
      SUBJECTS: A random sample of nursing mothers and their 5 months old infants (n =
      102). Data collection procedures: The mothers were questioned on their socio
      economic status, dietary habits, and their body mass index (BMI) was measured.
      Breast milk samples were collected from each mother. Milk lipid content and fatty
      acid composition were determined. RESULTS: Compared with milk from various
      countries, Congolese women's mature breast milk was low in lipid (28.70+/-11.33
      g/L) but rich in 8:0-14:0 FAs (25.97+/-8.17% of total FAs) and in polyunsaturated
      FAs (PUFAs), particularly n-3 PUFAs (2.39+/-0.68% of total FAs, mainly 18:3 and
      22:6). This was associated with the frequent consumption of high-carbohydrate
      foods (processed cassava roots, wheat bread, doughnuts) known to enhance 8:0-14:0
      FA biosynthesis, and with that of foods providing n-6 and n-3 EFAs such as
      freshwater and saltwater fish, vegetable oil, green leafy vegetables, and high
      fat fruit (peanuts, avocado, bushbutter). These foods were traditionally and
      locally produced. Milk lipid content was negatively related with mothers' BMI (P
      < 0.01) and varied with the frequency of consumption of certain foods
      corresponding to distinct dietary patterns. CONCLUSIONS: Lipid content and FA
      composition of Congolese breast milk were dependent on mother's nutritional
      status. However, despite an adequate EFA composition of breast milk, partially
      breast-fed 5 months old Congolese infants probably did not get enough n-6 and n-3
      EFAs from breast milk to meet their EFA requirements.

PMID- 9537301
TI  - Plasma total-homocysteine in anorexia nervosa.
AB  - OBJECTIVE: The measurement of plasma total-homocysteine (tHcy) as a marker of
      folate and cobalamin status in patients with anorexia nervosa. DESIGN: Plasma
      tHcy, folate, cobalamin and other determinants of tHcy of a random group of
      patients with anorexia nervosa were compared with our own reference values.
      SETTING: The study was performed at the tertiary children's Hospital Sant Joan de
      Deu. SUBJECTS: All the female adolescents (n=43) coming to the Hospital during a
      one-year period, who were diagnosed with anorexia nervosa. Reference values for
      tHcy were simultaneously performed with apparently healthy adolescents (by
      history and analytical data) who underwent presurgical analysis for minor
      interventions, and other magnitudes we used our own reference values.
      INTERVENTIONS: Plasma tHcy was measured by reverse phase HPLC with fluorescence
      detection of the SBDF derivatives. Folate and cobalamin concentrations were
      determined by radioimmunoassay. RESULTS: tHcy was significantly increased in
      anorexic patients compared to reference values (Mann-Whitney, P < 0.0001-0.001).
      Values were above reference range in 34% of patients, and high-normal range in
      53% of patients. tHcy concentrations lowered in 8 and 11 patients after
      nutritional rehabilitation. Cobalamin and folate were in the reference range
      except for one case. No significant correlation was found among tHcy, vitamins
      and other determinants of tHcy concentration. CONCLUSIONS: tHcy concentrations
      appear significantly increased in adolescents with anorexia nervosa, most
      probably owing to subclinical folate deficiency. This might be caused by both,
      intracellular folate deficiency and impaired availability. Abnormal plasma tHcy
      values were completely corrected after nutritional rehabilitation.

PMID- 9537302
TI  - Interpopulation and intrapopulation variability of nutrient intake in five
      regions of Japan.
AB  - OBJECTIVES: To determine the extent to which interpopulation (between-population)
      variance, relative to intrapopulation (within-population) variance, contribute to
      the total variability in nutrient intakes. DESIGN: Cross-sectional study.
      SETTING: Five Public Health Center districts in Japan. SUBJECTS: Two hundred and
      seven men and 183 spouses. INTERVENTIONS: A three-day weighed food record. MAIN
      OUTCOME MEASURES: The total variance in the consumption of 17 nutrient variables
      was partitioned by analysis of variance into its inter- and intrapopulation
      components separately for men and women. RESULTS: The percentage contribution of
      the interpopulation to total variance differed according to the nutrient; it was
      notable (8-17%) for total energy, carbohydrates, phosphorus, and sodium in both
      men and women, but was negligible (less than 4%) for micronutrients such as
      retinol, carotene, thiamin, riboflavin, niacin and ascorbic acid. The ratio of
      intra- to interpopulation variance was estimated for 31 nutrients (17 in men and
      14 in women). The point estimates of the ratio were larger than unity in all
      nutrients, and the lower limit of the 95% confidence intervals exceeded unity for
      all but 5 nutrients. Of the two sources of intrapopulation variation,
      intraindividual variance was larger than interindividual variance in most of the
      nutrient. CONCLUSIONS: The relative magnitude of interpopulation variation in
      dietary data can be used to quantify the range of exposure in ecological studies
      and to examine the heterogeneity of populations pooled for individual-based
      analysis.

PMID- 9537303
TI  - Comparison of in-vivo body composition using two Lunar dual-energy X-ray
      absorptiometers.
AB  - OBJECTIVE: To compare in-vivo composition analysis between two dual energy X-ray
      absorptiometers, a DPX and a DPX/L, from the same manufacturer (LUNAR), pre(Study
      A) and post(Study B) hardware changes on both absorptiometers. DESIGN: Comparison
      of (1) quality assurance (QA) data: air-counts low (38 keV), air-counts high (70
      keV), air-counts ratio, percent spillover, R-delrin; and (2) total body
      compartments: total body tissue (TBTISS), total body fat (TBF), percent total
      body fat (%TBF), total body lean (TBLEAN), total body bone mineral content
      (TBBMC) and total body bone mineral density (TBBMD), between the two
      absorptiometers. SETTING: Centre for Bone and Body Composition Research,
      University of Leeds. SUBJECTS: Study A, 14 normal subjects and Study B, a
      different cohort of 19 normal subjects, were scanned on both machines on the same
      day. RESULTS: In Study A, large significant differences were observed in the QA
      parameters between the two machines. The DPX, air-counts low and air-counts high,
      being 25% and 22% lower than the DPX/L. The Bland Altman method of analysis
      indicated that the DPX was significantly higher for TBTISS (0.3 kg), %TBF (2%)
      and TBF ( 1.4 kg) and correspondingly lower for TBLEAN (-1.0 kg). No significant
      difference was observed in TBBMC. After the hardware changes (Study B) a marked
      reduction in the differences in QA air-counts was observed. The DPX air-counts
      low was now 1% higher and air-counts high 8% lower than the DPX/L. The DPX had
      now only small significant negative differences for %TBF (-0.6%) and TBF (-0.4
      kg) and a small significant positive difference for TBLEAN (0.4 kg), compared to
      the DPX/L. TBBMC difference although slightly increased, was still non
      significant. CONCLUSIONS: The closer agreement observed in the QA parameters
      after the hardware changes was associated with a reduction in the mean
      differences, 95%CI of the mean differences and limits of agreement of the
      comparison of body composition analysis from the Lunar machines using the Bland
      Altman method. The study indicates that the QA limits set for bone mineral
      analysis may require more stringent limits for body composition.

PMID- 9537304
TI  - Effect of additional questions about fat on the validity of fat estimates from a
      food frequency questionnaire. Study Group of MRS SWEA.
AB  - OBJECTIVE: We studied whether the validity of fat estimates from food frequency
      questionnaires (FFQ) can be increased by using in nutrient calculation an
      additional qualitative information about the type of fat and reduced consumption
      of visible fat and skin. DESIGN: A random sample of women answered an 88-item
      self-administered FFQ and performed 4 x 1-week weighed dietary records (DR).
      SETTING: Uppsala County in central Sweden. SUBJECTS: One hundred and eighty-four
      women aged 30-77 y, with FFQ and complete DR; 73 women with subcutaneous adipose
      tissue (AT) samples. METHODS: Fat intake from the FFQ was calculated with/without
      use of qualitative information and compared to DR and fat composition of AT. MAIN
      OUTCOME MEASURES: Estimates of long-time intake of total fat, saturated,
      monounsaturated, polyunsaturated fat and ten specific fatty acids based on FFQ,
      DR and composition of AT. RESULTS: Mean absolute fat intake estimates based on
      FFQ (without vs with use of additional fat information) were 21.2 vs 20.2 g/d for
      saturated, 17.1 vs 16.0 g/d for monounsaturated and 7.3 vs 7.3 g/d for
      polyunsaturated fat. The Pearson correlation coefficient between the FFQ and AT
      for polyunsaturated fat was 0.65 vs 0.67. Corresponding correlation between the
      FFQ and DR was 0.40 vs 0.41; adjustment for energy intake increased this
      correlation from 0.40 to 0.52. CONCLUSIONS: The increase in the validity of fat
      estimates due to use of qualitative information about fat was negligible; energy
      adjustment had greater impact than asking additional questions.

PMID- 9537305
TI  - Are high-fat and low-fat consumers distinct phenotypes? Differences in the
      subjective and behavioural response to energy and nutrient challenges.
AB  - OBJECTIVE: To characterise the appetite control in habitual high fat (HF) and low
      fat (LF) phenotypes. DESIGN: Four treatment conditions for each subject group in
      a fully repeated 2 x 2 x 2 measures design. SETTING: The Human Appetite Research
      Unit at Leeds University, Psychology Department. SUBJECTS: Eight lean HF (mean %
      fat intake-46.7% daily energy) and eight lean LF (mean % fat intake - 29.9% daily
      energy) were recruited from the staff/student population of Leeds University.
      INTERVENTIONS: All subjects were provided with either a low (2129 kJ) or high
      (3801 kJ) energy meal at midday and the capacity for compensation was later
      measured by nutrient challenge (ad libitum consumption of either high fat or high
      CHO foods). Satiation and satiety were assessed by changes in energy and nutrient
      intakes, hunger, fullness and food preferences. RESULTS: The energy and nutrient
      manipulations gave rise to different levels in the rated intensity of hunger
      between HF and LF (P < 0.01). HF rated their baseline hunger at a higher level
      than LF, and the nutrient induced changes in hunger had a much greater amplitude.
      HF consumed significantly more energy from the high fat meals than from the high
      CHO meals (P < 0.05); this effect was not observed in LF. HF ate more energy and
      a greater weight of the high fat foods but less energy and smaller weight of the
      high CHO foods than did the LF. HF rated the high fat and high CHO foods equally
      satisfying, tasty and filling, whereas LF indicated a preference for high CHO
      foods (P < 0.05). CONCLUSIONS: The appetite control in habitual high and low fat
      consumers is different. HF 'passively overconsume' fat whereas this effect is
      weak in LF. The HF ate a constant weight of food whereas LF ate a more constant
      level of energy. HF could not distinguish between high and low fat foods
      suggesting that they were intrinsically insensitive or 'taste adapted' whereas LF
      were fat sensitive. The clear differences disclosed in response to signals
      generated by the characteristics of ingested food (weight, energy, nutrient
      composition, taste) suggest that habitual high and low fat consumers can be
      regarded as distinct behavioural phenotypes. The different styles of appetite
      control could arise from: (a) intrinsic physiological differences, or (b) a
      system which is adapted to deal with a particular type of diet.

PMID- 9537306
TI  - Black tea consumption does not protect low density lipoprotein from oxidative
      modification.
AB  - OBJECTIVE: To investigate the in vivo and in vitro effects of black tea on the
      oxidative modification of low density lipoprotein (LDL). DESIGN: The antioxidant
      activity of the tea was studied in vitro by measuring the resistance of the LDL
      to oxidative modification in the presence of copper. The effects of tea
      consumption in vivo were investigated in two settings. Firstly, to assess the
      acute effects of tea consumption, five fasting healthy subjects ingested 600 mls
      (50.7+/-5.4 mg flavonoids) of black tea and peripheral venous blood was collected
      at 0, 30, 60, 90, 120 and 180 min after consumption. Secondly, to assess the
      effects of chronic tea consumption, a randomised crossover trial of tea (126.8+/
      13.5 mg flavonoids) and coffee consumption was carried out in ten healthy
      subjects. RESULTS: Black tea extract increased the resistance of LDL in vitro in
      a concentration dependent manner. There was no significant change in total plasma
      antioxidant capacity or susceptibility of the LDL to oxidation over the 3 h
      period after consumption of black tea. The four-week crossover study in which
      coffee was used as a control against the black tea showed no significant
      difference in the total plasma antioxidant capacity or susceptibility of LDL to
      oxidation between the tea and coffee groups. Serum lipids, including total
      cholesterol, triglycerides, LDL cholesterol and HDL cholesterol did not change
      significantly throughout the study. CONCLUSIONS: The consumption of moderate
      quantities of black tea acutely or for one week does not increase plasma total
      antioxidant capacity or alter the susceptibility of LDL to oxidation.

PMID- 9537307
TI  - Obese women are less sensitive for the satiety effects of bombesin than lean
      women.
AB  - OBJECTIVE: The aim of this study was to investigate whether infusion of bombesin,
      when combined with a gastric preload, influence satiety and foot intake in obese
      and lean healthy women. DESIGN: Double blind, placebo controlled study. SETTING:
      Department of Gastroenterology, Leiden University Medical Center, The
      Netherlands. SUBJECTS: Obese (n = 7) and lean (n = 7) healthy women.
      INTERVENTIONS: Intravenous infusion of bombesin (0.09 nmol/kg ideal weight/h) or
      placebo for 165 min. Gastric preload of banana slices was administered at time 60
      min. Meal ingestion started at time 75 min (banana slices). Food intake was
      calculated and satiety was measured by visual analog scales. RESULTS: During
      infusion of bombesin the amount of food eaten by the lean individuals (193+/-37
      g) was significantly reduced compared to saline infusion (365+/-42 g, P < 0.05).
      However, bombesin induced no significant feeding suppression in obese women when
      compared to saline (241+/-46 vs 301+/-45 g, respectively). The decrease in food
      intake during bombesin infusion compared to saline was significantly greater in
      lean subjects (173+/-30 g) than in obese subjects (59+/-35 g; P < 0.05). Only in
      lean subjects subjective preprandial hunger feelings were significantly affected
      by bombesin infusion. CONCLUSIONS: Infusion of bombesin, when combined with a
      gastric preload, inhibits food intake and increases satiety in lean women. Obese
      women are less sensitive for these bombesin induced satiety effects.

PMID- 9537308
TI  - High fat versus high carbohydrate nutritional supplementation: a one year trial
      in stunted rural Gambian children.
AB  - OBJECTIVE: The study tests the hypothesis that a low daily fat intake may induce
      a negative fat balance and impair catch-up growth in stunted children between 3
      and 9y of age. DESIGN: Randomized case-control study. SETTING: Three rural
      villages of the West Kiang District, The Gambia. SUBJECTS: Three groups of 30
      stunted but not wasted children (height for age z-score < or = -2.0, weight for
      height z-score > or = -2.0) 3-9 y of age were selected by anthropometric survey.
      Groups were matched for age, sex, village, degree of stunting and season.
      INTERVENTION: Two groups were randomly assigned to be supplemented five days a
      week for one year with either a high fat (n = 29) or a high carbohydrate biscuit
      (n = 30) each containing approximately 1600 kJ. The third group was a non
      supplemented control group (n = 29). Growth, nutritional status, dietary intake,
      resting energy expenditure and morbidity were compared. RESULTS: Neither the high
      fat nor the high carbohydrate supplement had an effect on weight or height gain.
      The high fat supplement did slightly increase adipose tissue mass. There was no
      effect of supplementation on resting energy expenditure or morbidity. In
      addition, the annual growth rate was not associated with a morbidity score.
      CONCLUSIONS: Results show that neither a high fat nor a high carbohydrate
      supplement given during 12 months to stunted Gambian children induced catch-up
      growth. The authors suggest that an adverse effect of the environment on catch-up
      growth persists despite the nutritional interventions.

PMID- 9537309
TI  - Zinc supplementation, mental development and behaviour in low birth weight term
      infants in northeast Brazil.
AB  - OBJECTIVE: To test whether zinc supplementation reduces the deficits in mental
      development and behaviour that are found in term infants of low birth weight in
      the study population. DESIGN: A prospective double-blind, part-randomised
      efficacy trial. SETTING: A low-income population in Pernambuco, northeast Brazil,
      where the economy is largely dependent on sugar-cane production, and where over
      90% of deliveries occur in health facilities. SUBJECTS: During a 20-month period,
      all singleton, term infants weighing 1500-2499 g born to families of low income (
      < US $280/month) were enrolled at birth (n = 205). At 6 and 12-months, the
      numbers tested were 163 and 138 respectively. INTERVENTION: Infants born from
      January 1993-January 1994 were randomly assigned to receive daily, except
      Sundays, a placebo (n = 66) or 1 mg zinc (n = 68). Those born February-August
      1994 were given 5 mg zinc (n = 71). Supplementation was for eight weeks, starting
      at birth. Field workers visited each infant at home to administer the supplement.
      RESULTS: At 6 and 12-months, mental and psychomotor development was assessed with
      the Bayley Scales of Infant Development and no significant differences in the
      scores of the three groups were found. At 12-months, behaviour was also assessed
      on 5 ratings. Ratings were highest in infants given 5 mg zinc (P = 0.042).
      CONCLUSIONS: Zinc supplementation (5 mg/d) for eight weeks may reverse some of
      the poor behaviours, particularly responsiveness, exhibited by low birth weight
      infants. No amelioration of their mental and psychomotor deficits was found.

PMID- 9537310
TI  - Perils in free market genomics.

PMID- 9537311
TI  - Germline gene therapy 'must be spared excessive regulation'.

PMID- 9537312
TI  - Russian church and scientists lay revolutionary quarrels to rest.

PMID- 9537313
TI  - MAFF in a stew over food research plans.

PMID- 9537314
TI  - Novartis goes public with fraud dismissal.

PMID- 9537315
TI  - Patents, ownership and sovereignty.

PMID- 9537316
TI  - Life without leptin.

PMID- 9537317
TI  - Substance P equals pain substance?

PMID- 9537318
TI  - Microbial genomes opened up.

PMID- 9537319
TI  - A triploblast origin for Myxozoa?

PMID- 9537320
TI  - The complete genome of the hyperthermophilic bacterium Aquifex aeolicus.
AB  - Aquifex aeolicus was one of the earliest diverging, and is one of the most
      thermophilic, bacteria known. It can grow on hydrogen, oxygen, carbon dioxide,
      and mineral salts. The complex metabolic machinery needed for A. aeolicus to
      function as a chemolithoautotroph (an organism which uses an inorganic carbon
      source for biosynthesis and an inorganic chemical energy source) is encoded
      within a genome that is only one-third the size of the E. coli genome. Metabolic
      flexibility seems to be reduced as a result of the limited genome size. The use
      of oxygen (albeit at very low concentrations) as an electron acceptor is allowed
      by the presence of a complex respiratory apparatus. Although this organism grows
      at 95 degrees C, the extreme thermal limit of the Bacteria, only a few specific
      indications of thermophily are apparent from the genome. Here we describe the
      complete genome sequence of 1,551,335 base pairs of this evolutionarily and
      physiologically interesting organism.

PMID- 9537321
TI  - Somatosensory discrimination based on cortical microstimulation.
AB  - The sensation of flutter is produced when mechanical vibrations in the range of 5
      50Hz are applied to the skin. A flutter stimulus activates neurons in the primary
      somatosensory cortex (S1) that somatotopically map to the site of stimulation. A
      subset of these neurons-those with quickly adapting properties, associated with
      Meissner's corpuscles-are strongly entrained by periodic flutter vibrations,
      firing with a probability that oscillates at the input frequency. Hence, quickly
      adapting neurons provide a dynamic representation of such flutter stimuli.
      However, are these neurons directly involved in the perception of flutter? Here
      we investigate this in monkeys trained to discriminate the difference in
      frequency between two flutter stimuli delivered sequentially on the fingertips.
      Microelectrodes were inserted into area 3b of S1 and the second stimulus was
      substituted with a train of injected current pulses. Animals reliably indicated
      whether the frequency of the second (electrical) signal was higher or lower than
      that of the first (mechanical) signal, even though both frequencies changed from
      trial to trial. Almost identical results were obtained with periodic and
      aperiodic stimuli of equal average frequencies. Thus, the quickly adapting
      neurons in area 3b activate the circuit leading to the perception of flutter.
      Furthermore, as far as can be psychophysically quantified during discrimination,
      the neural code underlying the sensation of flutter can be finely manipulated, to
      the extent that the behavioural responses produced by natural and artificial
      stimuli are indistinguishable.

PMID- 9537322
TI  - Primary afferent tachykinins are required to experience moderate to intense pain.
AB  - The excitatory neurotransmitter glutamate coexists with the peptide known as
      substance P in primary afferents that respond to painful stimulation. Because
      blockers of glutamate receptors reliably reduce pain behaviour, it is assumed
      that 'pain' messages are mediated by glutamate action on dorsal horn neurons. The
      contribution of substance P, however, is still unclear. We have now disrupted the
      mouse preprotachykinin A gene (PPT-A), which encodes substance P and a related
      tachykinin, neurokinin A. We find that although the behavioural response to
      mildly painful stimuli is intact in these mice, the response to moderate to
      intense pain is significantly reduced. Neurogenic inflammation, which results
      from peripheral release of substance P and neurokinin A, is almost absent in the
      mutant mice. We conclude that the release of tachykinins from primary afferent
      pain-sensing receptors (nociceptors) is required to produce moderate to intense
      pain.

PMID- 9537323
TI  - Altered nociception, analgesia and aggression in mice lacking the receptor for
      substance P.
AB  - The peptide neurotransmitter substance P modulates sensitivity to pain by
      activating the neurokinin-1 (NK-1) receptor, which is expressed by discrete
      populations of neurons throughout the central nervous system. Substance P is
      synthesized by small-diameter sensory 'pain' fibres, and release of the peptide
      into the dorsal horn of the spinal cord following intense peripheral stimulation
      promotes central hyperexcitability and increased sensitivity to pain. However,
      despite the availability of specific NK-1 antagonists, the function of substance
      P in the perception of pain remains unclear. Here we investigate the effect of
      disrupting the gene encoding the NK-1 receptor in mice. We found that the mutant
      mice were healthy and fertile, but the characteristic amplification ('wind up')
      and intensity coding of nociceptive reflexes was absent. Although substance P did
      not mediate the signalling of acute pain or hyperalgesia, it was essential for
      the full development of stress-induced analgesia and for an aggressive response
      to territorial challenge, demonstrating that the peptide plays an unexpected role
      in the adaptive response to stress.

PMID- 9537324
TI  - A mutation in the human leptin receptor gene causes obesity and pituitary
      dysfunction.
AB  - The adipocyte-specific hormone leptin, the product of the obese (ob) gene,
      regulates adipose-tissue mass through hypothalamic effects on satiety and energy
      expenditure. Leptin acts through the leptin receptor, a single-transmembrane
      domain receptor of the cytokine-receptor family. In rodents, homozygous mutations
      in genes encoding leptin or the leptin receptor cause early-onset morbid obesity,
      hyperphagia and reduced energy expenditure. These rodents also show
      hypercortisolaemia, alterations in glucose homeostasis, dyslipidaemia, and
      infertility due to hypogonadotropic hypogonadisms. In humans, leptin deficiency
      due to a mutation in the leptin gene is associated with early-onset obesity. Here
      we describe a homozygous mutation in the human leptin receptor gene that results
      in a truncated leptin receptor lacking both the transmembrane and the
      intracellular domains. In addition to their early-onset morbid obesity, patients
      homozygous for this mutation have no pubertal development and their secretion of
      growth hormone and thyrotropin is reduced. These results indicate that leptin is
      an important physiological regulator of several endocrine functions in humans.

PMID- 9537325
TI  - E-cadherin germline mutations in familial gastric cancer.
AB  - The identification of genes predisposing to familial cancer is an essential step
      towards understanding the molecular events underlying tumorigenesis and is
      critical for the clinical management of affected families. Despite a declining
      incidence, gastric cancer remains a major cause of cancer death worldwide, and
      about 10% of cases show familial clustering. The relative contributions of
      inherited susceptibility and environmental effects to familial gastric cancer are
      poorly understood because little is known of the genetic events that predispose
      to gastric cancer. Here we describe the identification of the gene responsible
      for early-onset, histologically poorly differentiated, high grade, diffuse
      gastric cancer in a large kindred from New Zealand (Aotearoa). Genetic linkage
      analysis demonstrated significant linkage to markers flanking the gene for the
      calcium-dependent cell-adhesion protein E-cadherin. Sequencing of the E-cadherin
      gene revealed a G --> T nucleotide substitution in the donor splice consensus
      sequence of exon 7, leading to a truncated gene product. Diminished E-cadherin
      expression is associated with aggressive, poorly differentiated carcinomas.
      Underexpression of E-cadherin is a prognostic marker of poor clinical outcome in
      many tumour types, and restored expression of E-cadherin in tumour models can
      suppress the invasiveness of epithelial tumour cells. The role of E-cadherin in
      gastric cancer susceptibility was confirmed by identifying inactivating mutations
      in other gastric cancer families. In one family, a frameshift mutation was
      identified in exon 15, and in a second family a premature stop codon interrupted
      exon 13. These results describe, to our knowledge for the first time, a molecular
      basis for familial gastric cancer, and confirm the important role of E-cadherin
      mutations in cancer.

PMID- 9537326
TI  - Stabilization of wild-type p53 by hypoxia-inducible factor 1alpha.
AB  - Although hypoxia (lack of oxygen in body tissues) is perhaps the most
      physiological inducer of the wild-type p53 gene, the mechanism of this induction
      is unknown. Cells may detect low oxygen levels through a haem-containing sensor
      protein. The hypoxic state can be mimicked by using cobalt chloride and the iron
      chelator desferrioxamine: like hypoxia, cobalt chloride and desferrioxamine
      activate hypoxia-inducible factor 1alpha (HIF-1alpha), which stimulates the
      transcription of several genes that are associated with hypoxia. Here we show
      that these treatments induce accumulation of wild-type p53 through HIF-1alpha
      dependent stabilization of p53 protein. Induction of p53 does not occur in either
      a mutant hepatoma cell line that is unable to induce HIF-1alpha or embryonic stem
      cells derived from mice lacking HIF-1beta. HIF-1alpha is found in p53
      immunoprecipitates from MCF7 cells that express wild-type p53 and are either
      hypoxic or have been exposed to desferrioxamine. Similarly, anti-haemagglutinin
      immunoprecipitates from lysates of normoxic PC3M cells that had been co
      transfected with haemagglutinin-tagged HIF-1alpha and wild-type p53 also contain
      p53. Transfection of normoxic MCF7 cells with HIF-1alpha stimulates a co
      transfected p53-dependent reporter plasmid and increases the amount of endogenous
      p53. Our results suggest that hypoxic induction of transcriptionally active wild
      type p53 is achieved as a result of the stabilization of p53 by its association
      with HIF-1alpha.

PMID- 9537327
TI  - Enhanced responses to a DNA vaccine encoding a fusion antigen that is directed to
      sites of immune induction.
AB  - Viral infection and vaccination with DNA both induce similar immune responses to
      encoded antigens that are produced by the host. The availability of antigens in
      lymphoid organs is important in generating an immune response to viral challenge.
      Antigen availability may also be important in the response to DNA vaccines,
      because immune responses are stronger when antigen is secreted from DNA
      transfected cells. We directed antigen to lymphoid organs by vaccination with DNA
      encoding antigen-ligand fusion proteins. The two ligands examined bind to
      receptors that are present on high endothelial venule cells of lymph nodes or on
      antigen-presenting cells. Here we show that both the humoral and the cellular
      immune responses to a model DNA vaccine were enhanced using either antigen
      targeting strategy. Moreover, directing antigen to antigen-presenting cells
      speeded up, and altered the form of, the immune response. Directing antigen to
      sites of immune-response induction may represent a generic means of tailoring a
      potent and effective immune response to a DNA vaccine.

PMID- 9537329
TI  - Action at the edges in cancer research.

PMID- 9537328
TI  - Rhodopsin-family receptors associate with small G proteins to activate
      phospholipase D.
AB  - G-protein-coupled receptors of the rhodopsin family transduce many important
      neural and endocrine signals. These receptors activate heterotrimeric G proteins
      and in many cases also cause activation of phospholipase D, an enzyme that can be
      controlled by the small G proteins ARF and RhoA. Here we show that the activation
      of phospholipase D that is induced by many, but not all, Ca2+-mobilizing G
      protein-coupled receptors is sensitive to inhibitors of ARF and of RhoA.
      Receptors of this type were co-immunoprecipitated with ARF or RhoA on exposure to
      agonists, and the effects of GTP analogues on ligand binding to the receptor
      changed to a profile that is characteristic of small G proteins. These receptors
      contain the amino-acid sequence AsnProXXTyr in their seventh transmembrane
      domain, whereas receptors capable of activating phospholipase D without involving
      ARF contain the sequence AspProXXTyr. Mutation of this latter sequence to
      AsnProXXTyr in the gonadotropin-releasing hormone receptor conferred sensitivity
      to an inhibitor of ARF, and the reciprocal mutation in the 5-HT2A receptor for 5
      hydroxy-tryptamine reduced its sensitivity to the inhibitor. Receptors carrying
      the AsnProXXTyr motif thus seem to form functional complexes with ARF and RhoA.

PMID- 9537330
TI  - Seeking the bigger picture in the puzzle.

PMID- 9537331
TI  - Visionaries seek UK national strategy.

PMID- 9537332
TI  - Therapeutics: a glimpse of the future.

PMID- 9537333
TI  - Cardiovascular and Renal Advisory Panel of the FDA.

PMID- 9537334
TI  - Therapeutic angiogenesis in ischemic limbs.

PMID- 9537335
TI  - High-altitude pulmonary edema: an immunogenetically mediated disease?

PMID- 9537336
TI  - Constitutive expression of phVEGF165 after intramuscular gene transfer promotes
      collateral vessel development in patients with critical limb ischemia.
AB  - BACKGROUND: Preclinical studies have indicated that angiogenic growth factors can
      stimulate the development of collateral arteries, a concept called "therapeutic
      angiogenesis." The objectives of this phase 1 clinical trial were (1) to document
      the safety and feasibility of intramuscular gene transfer by use of naked plasmid
      DNA encoding an endothelial cell mitogen and (2) to analyze potential therapeutic
      benefits in patients with critical limb ischemia. METHODS AND RESULTS: Gene
      transfer was performed in 10 limbs of 9 patients with nonhealing ischemic ulcers
      (n=7/10) and/or rest pain (n=10/10) due to peripheral arterial disease. A total
      dose of 4000 microg of naked plasmid DNA encoding the 165-amino-acid isoform of
      human vascular endothelial growth factor (phVEGF165) was injected directly into
      the muscles of the ischemic limb. Gene expression was documented by a transient
      increase in serum levels of VEGF monitored by ELISA. The ankle-brachial index
      improved significantly (0.33+/-0.05 to 0.48+/-0.03, P=.02); newly visible
      collateral blood vessels were directly documented by contrast angiography in 7
      limbs; and magnetic resonance angiography showed qualitative evidence of improved
      distal flow in 8 limbs. Ischemic ulcers healed or markedly improved in 4 of 7
      limbs, including successful limb salvage in 3 patients recommended for below-knee
      amputation. Tissue specimens obtained from an amputee 10 weeks after gene therapy
      showed foci of proliferating endothelial cells by immunohistochemistry. PCR and
      Southern blot analyses indicated persistence of small amounts of plasmid DNA.
      Complications were limited to transient lower-extremity edema in 6 patients,
      consistent with VEGF enhancement of vascular permeability. CONCLUSIONS: These
      findings may be cautiously interpreted to indicate that intramuscular injection
      of naked plasmid DNA achieves constitutive overexpression of VEGF sufficient to
      induce therapeutic angiogenesis in selected patients with critical limb ischemia.

PMID- 9537337
TI  - Association of high-altitude pulmonary edema with the major histocompatibility
      complex.
AB  - BACKGROUND: A constitutional susceptibility has been suggested in the development
      of high-altitude pulmonary edema (HAPE) because HAPE generally affects healthy
      young people, some of whom suffer recurrent episodes. We examined whether
      immunogenetic susceptibility is present in HAPE-susceptible subjects. METHODS AND
      RESULTS: The frequencies of human leukocyte antigen (HLA) alleles in 28 male and
      2 female subjects with a history of HAPE were compared with those in 100 healthy
      volunteers. We assayed the HLA-A, -B, -C, -DR, and -DQ antigens serologically.
      The pulmonary hemodynamics on admission to the hospital and the ventilatory
      response to hypoxia and hypercapnia were retrospectively examined in 10 of the
      HAPE-susceptible subjects. HLA-DR6 was positive in 14 (46.7%) of the subjects
      with HAPE but only 16.0% of the control subjects (P=.0005), and HLA-DQ4 was
      positive in 12 (40.0%) of the subjects with HAPE but only 10.0% of the control
      subjects (P=.0001). HLA-DR6 or HLA-DQ4 was positive in 8 (100%) of the subjects
      with recurrent HAPE. The pulmonary arterial pressure on admission of the HLA-DR6
      positive subjects with HAPE was significantly higher than that of the HLA-DR6
      negative subjects with HAPE. CONCLUSIONS: There were significant associations of
      HAPE with HLA-DR6 and HLA-DQ4 and of pulmonary hypertension with HLA-DR6. An
      immunogenetic susceptibility, which is associated with HLA class II alleles
      located within the major histocompatibility complex, may underlie the development
      of HAPE, at least in some of its forms.

PMID- 9537338
TI  - Upregulation of endothelial nitric oxide synthase by HMG CoA reductase
      inhibitors.
AB  - BACKGROUND: Oxidized low-density lipoprotein (ox-LDL) causes endothelial
      dysfunction in part by decreasing the availability of endothelial nitric oxide
      (NO). Although HMG CoA reductase inhibitors restore endothelial function by
      reducing serum cholesterol levels, it is not known whether they can also directly
      upregulate endothelial NO synthase (ecNOS) activity. METHODS AND RESULTS: Human
      saphenous vein endothelial cells were treated with ox-LDL (50 microg/mL
      thiobarbituric acid reactive substances 12 to 16 nmol/mg) in the presence of HMG
      CoA reductase inhibitors simvastatin and lovastatin. In a time-dependent manner,
      ox-LDL decreased ecNOS mRNA and protein levels (91+/-4% and 67+/-8% reduction
      after 72 hours, respectively). Both simvastatin (1 micromol/L) and lovastatin (10
      micromol/L) upregulated ecNOS expression by 3.8-fold and 3.6-fold, respectively,
      and completely prevented its downregulation by ox-LDL. These effects of
      simvastatin on ecNOS expression correlated with changes in ecNOS activity.
      Although L-mevalonate alone did not affect ecNOS expression, cotreatment with L
      mevalonate completely reversed ecNOS upregulation by simvastatin. Actinomycin D
      studies revealed that simvastatin stabilized ecNOS mRNA (tau1/2, 43 versus 35
      hours). Nuclear run-on assays and transient transfection studies with a -1.6 kb
      ecNOS promoter construct showed that simvastatin did not affect ecNOS gene
      transcription. CONCLUSIONS: Inhibition of endothelial HMG CoA reductase
      upregulates ecNOS expression predominantly by posttranscriptional mechanisms.
      These findings suggest that HMG CoA reductase inhibitors may have beneficial
      effects in atherosclerosis beyond that attributed to the lowering of serum
      cholesterol by increasing ecNOS activity.

PMID- 9537339
TI  - Elevated circulating levels of C-C chemokines in patients with congestive heart
      failure.
AB  - BACKGROUND: Immunologic and inflammatory responses appear to play a pathogenic
      role in the development of congestive heart failure (CHF). Activation and
      migration of leukocytes to areas of inflammation are important factors in these
      immunologic responses. Because the C-C chemokines are potent chemoattractants of
      monocytes and lymphocytes and can modulate other functions of these cells (eg,
      generation of reactive oxygen species), we measured circulating levels of three C
      C chemokines in CHF. METHODS AND RESULTS: Levels of macrophage chemoattractant
      protein-1 (MCP-1), macrophage inflammatory protein- 1alpha (MIP-1alpha), and
      RANTES (regulated on activation normally T-cell expressed and secreted) were
      measured by enzyme immunoassays in 44 patients with CHF and 21 healthy control
      subjects. CHF patients had significantly elevated levels of all chemokines with
      the highest levels in New York Heart Association class IV, and MCP-1 and MIP
      1alpha levels were significantly inversely correlated with left ventricular
      ejection fraction. Elevated C-C chemokine levels were found independent of the
      cause of the heart failure, but MCP-1 levels were particularly raised in patients
      with coronary artery disease. Studies on cells isolated from peripheral blood
      suggested that platelets, CD3+ lymphocytes, and in particular, monocytes, might
      contribute to the elevated C-C chemokine levels in CHF. The increased MCP-1
      levels in CHF were correlated with increased monocyte activity reflected in an
      enhancing effect of serum from CHF patients on O2-generation in monocytes, which
      was inhibited by neutralizing antibodies against MCP-1. CONCLUSIONS: This first
      demonstration of increased circulating levels of C-C chemokines in CHF with
      particularly high levels in patients with severe disease may represent previously
      unrecognized pathogenic factors in CHF.

PMID- 9537340
TI  - Regional myocardial blood flow redistribution as a cause of postprandial angina
      pectoris.
AB  - BACKGROUND: Postprandial angina pectoris has been recognized for more than two
      centuries and can be identified in up to 10% of patients with chronic ischemic
      heart disease. Redistribution of myocardial blood flow, from a region supplied by
      a severely stenotic coronary artery to those supplied by less diseased or normal
      vessels, is a potential mechanism of postprandial angina. METHODS AND RESULTS: To
      test this hypothesis, we have determined the effects of a standard liquid meal on
      whole heart and regional myocardial blood flow, measured by means of dynamic
      positron emission tomography (PET) with 15O-labeled water in 14 patients with a
      reproducible history of postprandial angina and 7 matched control subjects. The
      standard liquid meal precipitated angina pectoris in all patients. Baseline whole
      heart blood flow was similar and increased normally after the meal in patients
      (0.97+/-0.14 to 1.14+/-0.25 mL.min(-1).g(-1), P<.04) as in control subjects
      (0.92+/-0.12 to 1.02+/-0.13 mL.min(-1).g(-1), P<.02). In contrast, the
      coefficient of variation of blood flow increased significantly after the standard
      liquid meal in patients (34+/-9%, P<.05 versus baseline) but not in control
      subjects (17+/-7%, P=NS versus baseline). In patients, analysis of regional
      myocardial blood flow demonstrated decreased myocardial blood flow in territories
      supplied by stenotic arteries (1.01+/-0.35 to 0.76+/-0.27 mL.min(-1).g(-1),
      P<.03), but there was an increase in blood flow in territories supplied by normal
      arteries (0.89+/-0.16 to 1.34+/-0.25 mL.min(-1).g(-1), P<.001) after the meal.
      CONCLUSIONS: The standard liquid meal induced angina pectoris in patients with
      coronary artery disease. Although whole heart blood flow increased appropriately
      for the greater cardiac work, there was a redistribution of regional blood flow
      from territories supplied by severely stenosed coronary arteries to those
      supplied by less diseased or normal arteries. This redistribution may be the
      cause of myocardial ischemia in postprandial angina.

PMID- 9537341
TI  - Use of reperfusion therapy for acute myocardial infarction in the United States:
      data from the National Registry of Myocardial Infarction 2.
AB  - BACKGROUND: There is clear evidence that reperfusion therapy improves survival in
      selected patients with an acute myocardial infarction. However, several studies
      have suggested that many patients with an acute myocardial infarction do not
      receive this therapy. Whether this underutilization occurs in patients
      appropriate for such therapy remains unclear. METHODS AND RESULTS: We examined
      the use of reperfusion therapy in patients with an acute myocardial infarction
      hospitalized at 1470 hospitals participating in the National Registry of
      Myocardial Infarction 2. We identified 84 663 patients who were eligible for
      reperfusion therapy as defined by diagnostic changes on the initial 12-lead ECG,
      presentation to the hospital within 6 hours from symptom onset, and no
      contraindications to thrombolytic therapy. Twenty-four percent of these eligible
      patients did not receive any form of reperfusion therapy (7.5% of all patients).
      When multivariate analyses were used, left bundle-branch block (odds ratio
      [OR]=0.22; 95% CI=0.20 to 0.24), lack of chest pain at presentation (OR=0.22; 95%
      CI=0.21 to 0.24), age >75 years (OR=0.40, 95% CI=0.36 to 0.43), female sex
      (OR=0.88, 95% CI=0.83 to 0.92), and various preexisting cardiovascular conditions
      were independent predictors that the patient would not receive reperfusion
      therapy. CONCLUSIONS: Reperfusion therapy may be underutilized in the United
      States. Increased use of reperfusion therapy could potentially reduce the
      unnecessarily high mortality rates observed in women, the elderly, and other
      patient groups with the highest risk of death from an acute myocardial
      infarction.

PMID- 9537342
TI  - Electrical stimulation versus coronary artery bypass surgery in severe angina
      pectoris: the ESBY study.
AB  - BACKGROUND: Spinal cord stimulation (SCS) has been shown to have antianginal and
      anti-ischemic effects in severe angina pectoris. The present study was performed
      to investigate whether SCS can be used as an alternative to coronary artery
      bypass grafting (CABG) in selected patient groups, ie, patients with no proven
      prognostic benefit from CABG and with an increased surgical risk. METHODS AND
      RESULTS: One hundred four patients were randomized (SCS, 53; CABG, 51). The
      patients were assessed with respect to symptoms, exercise capacity, ischemic ECG
      changes during exercise, rate-pressure product, mortality, and cardiovascular
      morbidity before and 6 months after the operation. Both groups had adequate
      symptom relief (P<.0001), and there was no difference between SCS and CABG. The
      CABG group had an increase in exercise capacity (P=.02), less ST-segment
      depression on maximum (P=.005) and comparable (P=.0009) workloads, and an
      increase in the rate-pressure product both at maximum (P=.0003) and comparable
      (P=.03) workloads compared with the SCS group. Eight deaths occurred during the
      follow-up period, 7 in the CABG group and 1 in the SCS group. On an intention-to
      treat basis, the mortality rate was lower in the SCS group (P=.02).
      Cerebrovascular morbidity was also lower in the SCS group (P=.03). CONCLUSIONS:
      CABG and SCS appear to be equivalent methods in terms of symptom relief in this
      group of patients. Effects on ischemia, morbidity, and mortality should be
      considered in the choice of treatment method. Taking all factors into account, it
      seems reasonable to conclude that SCS may be a therapeutic alternative for
      patients with an increased risk of surgical complications.

PMID- 9537343
TI  - Return cycle mapping after entrainment of ventricular tachycardia.
AB  - BACKGROUND: The central common pathway, which is the target for ablation in
      reentrant ventricular tachycardia, can be localized by entrainment mapping
      techniques. However, localization of the pathway is not always possible because
      of the elevated pacing threshold and the low voltage and fractionated potentials
      at the pathway. We examined whether return cycle mapping after entrainment
      localizes the pathway without pacing at the pathway or recording the potentials
      from the pathway and determined the required electrode resolution to localize the
      pathway. METHODS AND RESULTS: Epicardial mapping was performed with 253 unipolar
      electrodes during and after entrainment of 13 morphologies of ventricular
      tachycardia that were induced in dogs 4 days after infarction. The return cycle
      was calculated by subtracting the first activation time from the second
      activation time after the last stimulus and the return cycle distribution map was
      constructed for each stimulation site. The return cycle isochrones equal to the
      ventricular tachycardia cycle length converged on the lines of conduction block
      irrespective of the stimulation site, and the central common pathway was
      localized at the region between the intersections of the return cycle isochrones
      after entrainment from different stimulation sites. The potentials from the
      central common pathway were not required to localize the pathway, and the mapping
      accuracy did not change with or without analysis of the potentials from the
      pathway. According to the correlation between the electrode resolution and the
      mapping accuracy, an interelectrode distance of 8.5 mm was estimated as
      sufficient resolution for successful tachycardia termination during
      radiofrequency ablation guided by return cycle mapping. CONCLUSIONS: Return cycle
      mapping after entrainment localizes the central common pathway without pacing at
      the pathway or recording the potentials from the pathway. This new mapping
      technique could improve the success rate of the ablative procedures.

PMID- 9537344
TI  - Linear atrial ablations in a canine model of chronic atrial fibrillation:
      morphological and electrophysiological observations.
AB  - BACKGROUND: To test the hypothesis that susceptibility to sustained atrial
      fibrillation may be decreased by creation of linear atrial ablations, we
      established a canine model of chronic atrial fibrillation and used a novel
      catheter design to create atrial ablations. METHODS AND RESULTS: Chronic atrial
      fibrillation was induced in 16 dogs by creation of mitral regurgitation and rapid
      pacing of the atria. Temperature-controlled radiofrequency ablations were
      attempted along empirically derived, preselected atrial target sites in 11 dogs
      (ablation group), and a sham procedure was performed in 5 dogs (control group).
      Follow-up electrophysiology study and pathological examination were conducted
      13+/-5 days after the initial procedure. Immediately after ablation, sustained
      atrial fibrillation could be initiated in 1 of 9 surviving ablation dogs and 5 of
      5 controls (P=.004). Four dogs died within 24 hours of the procedure. Permanent
      pacing was required in 4 dogs. At follow-up, 0 of 7 ablation dogs and 5 of 5
      controls had atrial fibrillation (P=.001). Furthermore, 2 of 7 ablation dogs had
      sustained atrial tachycardias, one of which was successfully ablated.
      Pathological examination demonstrated frequent incomplete lesion sets and
      discontinuous lesions. CONCLUSIONS: In this model, a reduction in the
      susceptibility to sustained atrial fibrillation can be achieved by long linear
      atrial ablations created with specially designed coil electrode catheters.
      Complete lesion continuity was not required to achieve a therapeutic effect.

PMID- 9537345
TI  - Reversal of reflex-induced myocardial ischemia by median nerve stimulation: a
      feline model of electroacupuncture.
AB  - BACKGROUND: Acupuncture is reported to reduce myocardial ischemia, arrhythmias,
      and hypertension. To investigate the physiological mechanisms underlying these
      observations, a model of reflex-induced, reversible myocardial ischemia was
      developed to test the effects of median nerve stimulation as a surrogate for
      electroacupuncture. METHODS AND RESULTS: Chloralose-anesthetized cats were
      instrumented to measure arterial blood pressure, left ventricular pressure, left
      ventricular dP/dt, heart rate, left anterior descending (LAD) coronary blood
      velocity, and regional wall motion. The LAD artery either was partially occluded
      or a small diagonal branch was ligated. Subsequently, transient reflex activation
      of the cardiovascular system was evoked by application of bradykinin (typically 1
      microg/mL) to the gallbladder, which significantly increased myocardial oxygen
      demand (double product), left ventricular dP/dt, and coronary blood velocity and
      caused ischemia-induced regional dysfunction, evidenced by significant (P<.05)
      reduction in normalized wall thickening (10.7+/-4.2% versus -23.6+/-2.9%; control
      versus ischemia; n=7). However, when median nerves were stimulated with low
      frequency (5 Hz) to mimic electroacupuncture, bradykinin-induced change in
      normalized wall thickening was significantly improved (-23.6+/-2.9% versus 9.8+/
      4.9%; ischemia versus median nerve stimulation, P<.05) and remained augmented >
      or = 1 hour. Results were similar in partial and complete occlusion groups.
      Significant improvement in wall thickening was associated with unchanged
      increment of coronary blood velocity and significantly diminished increments of
      double product and diastolic blood pressure. CONCLUSIONS: These results suggest
      that stimulation of the median nerve to mimic electroacupuncture diminishes
      regional myocardial ischemia triggered by a sympathetically mediated increase in
      cardiac oxygen demand. The mechanism of this effect is related to reduction in
      cardiac oxygen demand, secondary to a diminished pressor response. These data
      provide the first documentation of the physiological mechanisms underlying the
      possible beneficial effect of electroacupuncture in the context of restricted
      coronary blood flow and augmented myocardial oxygen demand.

PMID- 9537346
TI  - Acute coronary syndromes: unstable angina and non-Q-wave myocardial infarction.

PMID- 9537347
TI  - Images in cardiovascular medicine. Anatomically corrected malposition of the
      great arteries [S,D,L].

PMID- 9537348
TI  - Images in cardiovascular medicine. Discordance between coronary angiography and
      intracoronary ultrasound.

PMID- 9537349
TI  - Is measurement of cyclic guanosine monophosphate in plasma or urine suitable for
      assessing in vivo nitric oxide production?

PMID- 9537350
TI  - Effects of ischemic preconditioning.

PMID- 9537351
TI  - Effects of exercise during long-term support with a left ventricular assist
      device.

PMID- 9537352
TI  - A fast and accurate method for genotyping the angiotensin-converting enzyme I/D
      polymorphism.

PMID- 9537353
TI  - Delayed profound thrombocytopenia after c7E3 Fab (abciximab) therapy.

PMID- 9537354
TI  - Xanthomonas campestris pv. campestris gum mutants: effects on xanthan
      biosynthesis and plant virulence.
AB  - Xanthan is an industrially important exopolysaccharide produced by the
      phytopathogenic, gram-negative bacterium Xanthomonas campestris pv. campestris.
      It is composed of polymerized pentasaccharide repeating units which are assembled
      by the sequential addition of glucose-1-phosphate, glucose, mannose, glucuronic
      acid, and mannose on a polyprenol phosphate carrier (L. Ielpi, R. O. Couso, and
      M. A. Dankert, J. Bacteriol. 175:2490-2500, 1993). A cluster of 12 genes in a
      region designated xpsI or gum has been suggested to encode proteins involved in
      the synthesis and polymerization of the lipid intermediate. However, no
      experimental evidence supporting this suggestion has been published. In this
      work, from the biochemical analysis of a defined set of X. campestris gum
      mutants, we report experimental data for assigning functions to the products of
      the gum genes. We also show that the first step in the assembly of the lipid
      linked intermediate is severely affected by the combination of certain gum and
      non-gum mutations. In addition, we provide evidence that the C-terminal domain of
      the gumD gene product is sufficient for its glucosyl-1-phosphate transferase
      activity. Finally, we found that alterations in the later stages of xanthan
      biosynthesis reduce the aggressiveness of X. campestris against the plant.

PMID- 9537355
TI  - A surface-exposed region of a novel outer membrane protein (P66) of Borrelia spp.
      is variable in size and sequence.
AB  - A model of the 66-kDa outer membrane protein (P66) of Lyme disease Borrelia spp.
      predicts a surface-exposed loop near the C terminus. This region contains an
      antigen commonly recognized by sera from Lyme disease patients. In the present
      study, this region of P66 and homologous proteins of other Borrelia spp. were
      further investigated by using monoclonal antibodies, epitope mapping of P66 of
      Borrelia burgdorferi, and DNA sequencing. A monoclonal antibody specific for B.
      burgdorferi bound to the portion of P66 that was accessible to proteolysis in
      situ. The linear epitope for the antibody was mapped within a variable segment of
      the surface-exposed region. To further study this protein, the complete gene of
      Borrelia hermsii for a protein homologous to P66 was cloned. The deduced protein
      was 589 amino acids in length and 58% identical to P66 of B. burgdorferi. The B.
      hermsii P66 protein was predicted to have a surface-exposed region in the same
      location as that of B. burgdorferi's P66 protein. With primers designed on the
      basis of conserved sequences and PCR, we identified and cloned the same regions
      of P66 proteins of Borrelia turicatae, Borrelia parkeri, Borrelia coriaceae, and
      Borrelia anserina. The deduced protein sequences from all species demonstrated
      two conserved hydrophobic regions flanking a surface-exposed loop. The loop
      sequences were highly variable between different Borrelia spp. in both sequence
      and size, varying between 35 and 45 amino acids. Although the actual function of
      P66 of Borrelia spp. is unknown, the results suggest that its surface-exposed
      region is subject to selective pressure.

PMID- 9537356
TI  - Characterization of dnaC2 and dnaC28 mutants by flow cytometry.
AB  - Escherichia coli strains containing thermosensitive dnaC alleles were studied by
      flow cytometry. Strains containing either the dnaC2 or dnaC28 allele were shifted
      between different temperatures, and DNA content distributions were gathered.
      Inhibition of initiation of chromosome replication at nonpermissive temperature,
      as well as reinitiation of replication at permissive temperature, were found to
      be affected by a number of parameters. These included the choice of permissive
      and nonpermissive temperatures, the length of the time of incubation at the
      nonpermissive temperature, the growth medium, the type of temperature shift used
      for reinitiation of replication (transient or nontransient), the genetic
      background of the host cell, and the cell concentration. Reinitiation of
      replication required neither transcription nor translation, whereas the
      elongation stage of replication was dependent upon ongoing protein synthesis in
      the mutants. Efficient use of dnaC mutants for cell cycle studies is discussed.

PMID- 9537357
TI  - The CIRCE element and its putative repressor control cell cycle expression of the
      Caulobacter crescentus groESL operon.
AB  - The groESL operon is under complex regulation in Caulobacter crescentus. In
      addition to strong induction after exposure to heat shock, under physiological
      growth conditions, its expression is subject to cell cycle control. Transcription
      and translation of the groE genes occur primarily in predivisional cells, with
      very low levels of expression in stalked cells. The regulatory region of groESL
      contains both a sigma32-like promoter and a CIRCE element. Overexpression of C.
      crescentus sigma32 gives rise to higher levels of GroEL and increased levels of
      the groESL transcript coming from the sigma32-like promoter. Site-directed
      mutagenesis in CIRCE has indicated a negative role for this cis-acting element in
      the expression of groESL only at normal growth temperatures, with a minor effect
      on heat shock induction. Furthermore, groESL-lacZ transcription fusions carrying
      mutations in CIRCE are no longer cell cycle regulated. Analysis of an hrcA null
      strain, carrying a disruption in the gene encoding the putative repressor that
      binds to the CIRCE element, shows constitutive synthesis of GroEL throughout the
      Caulobacter cell cycle. These results indicate a negative role for the hrcA gene
      product and the CIRCE element in the temporal control of the groESL operon.

PMID- 9537358
TI  - An archaeal aerotaxis transducer combines subunit I core structures of eukaryotic
      cytochrome c oxidase and eubacterial methyl-accepting chemotaxis proteins.
AB  - Signal transduction in the archaeon Halobacterium salinarum is mediated by three
      distinct subfamilies of transducer proteins. Here we report the complete htrVIII
      gene sequence and present analysis of the encoded primary structure and its
      functional features. HtrVIII is a 642-amino-acid protein and belongs to
      halobacterial transducer subfamily B. At the N terminus, the protein contains six
      transmembrane segments that exhibit homology to the heme-binding sites of the
      eukaryotic cytochrome c oxidase. The C-terminal domain has high homology with the
      eubacterial methyl-accepting chemotaxis protein. The HtrVIII protein mediates
      aerotaxis: a strain with a deletion of the htrVIII gene loses aerotaxis, while an
      overproducing strain exhibits stronger aerotaxis. We also demonstrate that
      HtrVIII is a methyl-accepting protein and demethylates during the aerotaxis
      response.

PMID- 9537359
TI  - The cell wall-anchored Streptomyces reticuli avicel-binding protein (AbpS) and
      its gene.
AB  - Streptomyces reticuli produces a 35-kDa cellulose-binding protein (AbpS) which
      interacts strongly with crystalline forms of cellulose (Avicel, bacterial
      microcrystalline cellulose, and tunicin cellulose); other polysaccharides are
      recognized on weakly (chitin and Valonia cellulose) or not at all (xylan, starch,
      and agar). The protein could be purified to homogeneity due to its affinity to
      Avicel. After we sequenced internal peptides, the corresponding gene was
      identified by reverse genetics. In vivo labelling experiments with fluorescein
      isothiocyanate (FITC), FITC-labelled secondary antibodies, or proteinase K
      treatment revealed that the anchored AbpS protrudes from the surfaces of the
      hyphae. When we investigated the hydrophobicity of the deduced AbpS, one putative
      transmembrane segment was predicted at the C terminus. By analysis of the
      secondary structure, a large centrally located alpha-helix which has weak
      homology to the tropomyosin protein family was found. Physiological studies
      showed that AbpS is synthesized during the late logarithmic phase, independently
      of the carbon source.

PMID- 9537360
TI  - The ars operon in the skin element of Bacillus subtilis confers resistance to
      arsenate and arsenite.
AB  - The Bacillus subtilis skin element confers resistance to arsenate and arsenite.
      The ars operon in the skin element contains four genes in the order arsR, ORF2,
      arsB, and arsC. Three of these genes are homologous to the arsR, arsB, and arsC
      genes from the staphylococcal plasmid pI258, while no homologs of ORF2 have been
      found. Inactivation of arsR, arsB, or arsC results in either constitutive
      expression of ars, an arsenite- and arsenate-sensitive phenotype, or an arsenate
      sensitive phenotype, respectively. These results suggest that ArsR, ArsB, and
      ArsC function as a negative regulator, a membrane-associated protein need for
      extrusion of arsenite, and arsenate reductase, respectively. Expression of the
      ars operon was induced by arsenate, arsenite, and antimonite. Northern
      hybridization and primer extension analysis showed that synthesis of a full
      length ars transcript of about 2.4 kb was induced by arsenate and that the ars
      promoter contains sequences that resemble the -10 and -35 regions of promoters
      that are recognized by E sigmaA.

PMID- 9537361
TI  - Characterization of the cvaA and cvi promoters of the colicin V export system:
      iron-dependent transcription of cvaA is modulated by downstream sequences.
AB  - Secretion of the Escherichia coli toxin colicin V was previously determined to be
      iron regulated via the Fur (ferric uptake regulator) protein, based on studies in
      fur mutants. The iron dependence of transcription and expression of cvaA, which
      encodes a transporter accessory protein, and cvi, encoding the colicin V immunity
      protein, was assessed under conditions of iron excess or depletion. Immunoblots
      showed that production of both Cvi and CvaA is iron dependent. The iron-dependent
      transcriptional start for cvaA identified by primer extension and S1 nuclease
      analysis, P1, lies 320 bp upstream of the translational start and is associated
      with a newly identified Fur binding site. Beta-galactosidase activity in
      transcriptional lacZ fusions with the P1 promoter alone is higher than with
      downstream sequences present and is induced 10-fold by iron depletion. Including
      immediate downstream regions with P1 enhances activity from P1 even more but
      reduces the induction by iron depletion fivefold. Including subsequent downstream
      sequences, however, down-modulates overall transcription from P1 almost fourfold.
      Deletion of a long stem-loop structure in this region alleviates the down
      modulation by increasing transcription, indicating that the sequences or
      structure of this element may contribute to this down-regulation.
      Characterization of the cvi promoter by primer extension showed that it resides
      where predicted, about 50 bp upstream of cvi associated with a previously
      identified Fur binding site. The cvi promoter is also inducible by iron
      depletion. The modulating sequences from cvaA were placed downstream of the cvi
      promoter to test their effects in transcriptional fusions of the cvi promoter to
      lacZ. The fusion results showed that these sequences also modulate transcription
      of the cvi promoter in a manner similar to that of the cvaA promoter. The
      potential for up- and down-regulation within the long untranslated region
      downstream of the cvaA promoter suggests a novel mechanism that fine-tunes
      expression of the colicin V secretion genes.

PMID- 9537362
TI  - Forespore expression and processing of the SigE transcription factor in wild-type
      and mutant Bacillus subtilis.
AB  - SigmaE is a mother cell-specific transcription factor of sporulating Bacillus
      subtilis that is derived from an inactive precursor protein (pro-sigmaE). To
      examine the process that prevents sigmaE activity from developing in the
      forespore, we fused the sigmaE structural gene (sigE) to forespore-specific
      promoters (PdacF and PspoIIIG), placed these fusions at sites on the B. subtilis
      chromosome which translocate into the forespore either early or late, and used
      Western blot analysis to monitor SigE accumulation and pro-sigmaE processing.
      sigE alleles, placed at sites which entered the forespore early, were found to
      generate more protein product than the same fusion placed at a late entering
      site. SigE accumulation and processing in the forespore were enhanced by null
      mutations in spoIIIE, a gene whose product is essential for translocation of the
      distal portion of the B. subtilis chromosome into the forespore. In other
      experiments, a chimera of pro-sigmaE and green fluorescence protein, previously
      shown to be unprocessed if it is synthesized within the forespore, was found to
      be processed in this compartment if coexpressed with the gene for the pro-sigmaE
      processing enzyme, SpoIIGA. The need for spoIIGA coexpression is obviated in the
      absence of SpoIIIE. We interpret these results as evidence that selective
      degradation of both SigE and SpoIIGA prevent mature sigmaE from accumulating in
      the forespore compartment of wild-type B. subtilis. Presumably, a gene(s) located
      at a site that is distal to the origin of chromosome transfer is responsible for
      this phenomenon when it is translocated and expressed in the forespore.

PMID- 9537363
TI  - Characterization of the bvgR locus of Bordetella pertussis.
AB  - Bordetella pertussis, the causative agent of whooping cough, produces a wide
      array of factors that are associated with its ability to cause disease. The
      expression and regulation of these virulence factors is dependent upon the bvg
      locus (originally designated the vir locus), which encodes two proteins: BvgA, a
      23-kDa cytoplasmic protein, and BvgS, a 135-kDa transmembrane protein. It is
      proposed that BvgS responds to environmental signals and interacts with BvgA, a
      transcriptional regulator which upon modification by BvgS binds to specific
      promoters and activates transcription. An additional class of genes is repressed
      by the bvg locus. Expression of this class, the bvg-repressed genes (vrgs [for
      vir-repressed genes]), is reduced under conditions in which expression of the
      aforementioned bvg-activated virulence factors is maximal; this repression is
      dependent upon the presence of an intact bvgAS locus. We have previously
      identified a locus required for regulation of all of the known bvg-repressed
      genes in B. pertussis. This locus, designated bvgR, maps to a location
      immediately downstream of bvgAS. We have undertaken deletion and complementation
      studies, as well as sequence analysis, in order to identify the bvgR open reading
      frame and identify the cis-acting sequences required for regulated expression of
      bvgR. Studies utilizing transcriptional fusions of bvgR to the gene encoding
      alkaline phosphatase have demonstrated that bvgR is activated at the level of
      transcription and that this activation is dependent upon an intact bvgAS locus.

PMID- 9537364
TI  - Characterization of Rhizobium leguminosarum exopolysaccharide glycanases that are
      secreted via a type I exporter and have a novel heptapeptide repeat motif.
AB  - The prsDE genes encode a type I protein secretion system required for the
      secretion of the nodulation protein NodO and at least three other proteins from
      Rhizobium leguminosarum bv. viciae. At least one of these proteins was predicted
      to be a glycanase involved in processing of bacterial exopolysaccharide (EPS).
      Two strongly homologous genes (plyA and plyB) were identified as encoding
      secreted proteins with polysaccharide degradation activity. Both PlyA and PlyB
      degrade EPS and carboxymethyl cellulose (CMC), and these extracellular activities
      are absent in a prsD (protein secretion) mutant. The plyA gene is upstream of
      prsD but appears to be expressed at a very low level (if at all) in cultured
      bacteria. A plyB::Tn5 mutant has a very large reduction in degradation of EPS and
      CMC. Cultures of plyB mutants contained an increased ratio of EPS repeat units to
      reducing ends, indicating that the EPS was present in a longer-chain form, and
      this correlated with a significant increase in culture viscosity. Thus, PlyB may
      play a role in processing of EPS. Analysis of the symbiotic properties of a plyA
      plyB double mutant revealed that these genes are not required for symbiotic
      nitrogen fixation and that nodulation was not significantly affected. PlyA and
      PlyB are similar to bacterial and fungal polysaccharide lyases; they contain 10
      copies of what we propose as a novel heptapeptide repeat motif that may
      constitute a fold similar to that found in the family of extracellular pectate
      lyases. PlyA and PlyB lack the Ca2+-binding RTX nonapeptide repeat motifs usually
      found in proteins secreted via type I systems. We propose that PlyA and PlyB are
      members of a new family of proteins secreted via type I secretion systems and
      that they are involved in processing of EPS.

PMID- 9537365
TI  - The Saccharomyces cerevisiae SCS2 gene product, a homolog of a synaptobrevin
      associated protein, is an integral membrane protein of the endoplasmic reticulum
      and is required for inositol metabolism.
AB  - The Saccharomyces cerevisiae SCS2 gene has been cloned as a suppressor of
      inositol auxotrophy of CSE1 and hac1/ire15 mutants (J. Nikawa, A. Murakami, E.
      Esumi, and K. Hosaka, J. Biochem. 118:39-45, 1995) and has homology with a
      synaptobrevin/VAMP-associated protein, VAP-33, cloned from Aplysia californica
      (P. A. Skehel, K. C. Martin, E. R. Kandel, and D. Bartsch, Science 269:1580-1583,
      1995). In this study we have characterized an SCS2 gene product (Scs2p). The
      product has a molecular mass of 35 kDa and is C-terminally anchored to the
      endoplasmic reticulum, with the bulk of the protein located in the cytosol. The
      disruption of the SCS2 gene causes yeast cells to exhibit inositol auxotrophy at
      temperatures of above 34 degrees C. Genetic studies reveal that the
      overexpression of the INO1 gene rescues the inositol auxotrophy of the SCS2
      disruption strain. The significant primary structural feature of Scs2p is that
      the protein contains the 16-amino-acid sequence conserved in yeast and mammalian
      cells. The sequence is required for normal Scs2p function, because a mutant Scs2p
      that lacks the sequence does not complement the inositol auxotrophy of the SCS2
      disruption strain. Therefore, the Scs2p function might be conserved among
      eukaryotic cells.

PMID- 9537366
TI  - Roles of the catalytic domain and two cellulose binding domains of
      Thermomonospora fusca E4 in cellulose hydrolysis.
AB  - Thermomonospora fusca E4 is an unusual 90.4-kDa endocellulase comprised of a
      catalytic domain (CD), an internal family IIIc cellulose binding domain (CBD), a
      fibronectinlike domain, and a family II CBD. Constructs containing the CD alone
      (E4-51), the CD plus the family IIIc CBD (E4-68), and the CD plus the
      fibronectinlike domain plus the family II CBD (E4-74) were made by using
      recombinant DNA techniques. The activities of each purified protein on bacterial
      microcrystalline cellulose (BMCC), filter paper, swollen cellulose, and
      carboxymethyl cellulose were measured. Only the whole enzyme, E4-90, could reach
      the target digestion of 4.5% on filter paper. Removal of the internal family IIIc
      CBD (E4-51 and E4-74) decreased activity markedly on every substrate. E4-74 did
      bind to BMCC but had almost no hydrolytic activity, while E4-68 retained 32% of
      the activity on BMCC even though it did not bind. A low-activity mutant of one of
      the catalytic bases, E4-68 (Asp55Cys), did bind to BMCC, although E4-51
      (Asp55Cys) did not. The ratios of soluble to insoluble reducing sugar produced
      after filter paper hydrolysis by E4-90, E4-68, E4-74, and E4-51 were 6.9, 3.5,
      1.3, and 0.6, respectively, indicating that the family IIIc CBD is important for
      E4 processivity.

PMID- 9537367
TI  - Mutation of a gene encoding a putative glycoprotease leads to reduced salt
      tolerance, altered pigmentation, and cyanophycin accumulation in the
      cyanobacterium Synechocystis sp. strain PCC 6803.
AB  - The salt-sensitive mutant 549 of the cyanobacterium Synechocystis sp. strain PCC
      6803 was genetically and physiologically characterized. The mutated site and
      corresponding wild-type site were cloned and partially sequenced. The genetic
      analysis revealed that during the mutation about 1.8 kb was deleted from the
      chromosome of mutant 549. This deletion affected four open reading frames: a gcp
      gene homolog, the psaFJ genes, and an unknown gene. After construction of mutants
      with single mutations, only the gcp mutant showed a reduction in salt tolerance
      comparable to that of the initial mutant, indicating that the deletion of this
      gene was responsible for the salt sensitivity and that the other genes were of
      minor importance. Besides the reduced salt tolerance, a remarkable change in
      pigmentation was observed that became more pronounced in salt-stressed cells. The
      phycobilipigment content decreased, and that of carotenoids increased.
      Investigations of changes in the ultrastructure revealed an increase in the
      amount of characteristic inclusion bodies containing the high-molecular-weight
      nitrogen storage polymer cyanophycin (polyaspartate and arginine). The salt
      induced accumulation of cyanophycin was confirmed by chemical estimations. The
      putative glycoprotease encoded by the gcp gene might be responsible for the
      degradation of cyanophycin in Synechocystis. Mutation of this gene leads to
      nitrogen starvation of the cells, accompanied by characteristic changes in
      pigmentation, ultrastructure, and salt tolerance level.

PMID- 9537368
TI  - The TolQRA proteins are required for membrane insertion of the major capsid
      protein of the filamentous phage f1 during infection.
AB  - Infection of Escherichia coli by the filamentous bacteriophage f1 is initiated by
      interaction of the end of the phage particle containing the gene III protein with
      the tip of the F conjugative pilus. This is followed by the translocation of the
      phage DNA into the cytoplasm and the insertion of the major phage capsid protein,
      pVIII, into the cytoplasmic membrane. DNA transfer requires the chromosomally
      encoded TolA, TolQ, and TolR cytoplasmic membrane proteins. By using radiolabeled
      phages, it can be shown that no pVIII is inserted into the cytoplasmic membrane
      when the bacteria contain null mutations in tolQ, -R and -A. The rate of
      infection can be varied by using bacteria expressing various mutant TolA
      proteins. Analysis of the infection process in these strains demonstrates a
      direct correlation between the rate of infection and the incorporation of
      infecting bacteriophage pVIII into the cytoplasmic membrane.

PMID- 9537369
TI  - The Rhizobium etli rpoN locus: DNA sequence analysis and phenotypical
      characterization of rpoN, ptsN, and ptsA mutants.
AB  - The rpoN region of Rhizobium etli was isolated by using the Bradyrhizobium
      japonicum rpoN1 gene as a probe. Nucleotide sequence analysis of a 5,600-bp DNA
      fragment of this region revealed the presence of four complete open reading
      frames (ORFs), ORF258, rpoN, ORF191, and ptsN, coding for proteins of 258, 520,
      191, and 154 amino acids, respectively. The gene product of ORF258 is homologous
      to members of the ATP-binding cassette-type permeases. ORF191 and ptsN are
      homologous to conserved ORFs found downstream from rpoN genes in other bacterial
      species. Unlike in most other microorganisms, rpoN and ORF191 are separated by
      approximately 1.6 kb. The R. etli rpoN gene was shown to control in free-living
      conditions the production of melanin, the activation of nifH, and the metabolism
      of C4-dicarboxylic acids and several nitrogen sources (ammonium, nitrate,
      alanine, and serine). Expression of the rpoN gene was negatively autoregulated
      and occurred independently of the nitrogen source. Inactivation of the ptsN gene
      resulted in a decrease of melanin synthesis and nifH expression. In a search for
      additional genes controlling the synthesis of melanin, an R. etli mutant carrying
      a Tn5 insertion in ptsA, a gene homologous to the Escherichia coli gene coding
      for enzyme I of the phosphoenolpyruvate:sugar phosphotransferase system, was
      obtained. The R. etli ptsA mutant also displayed reduced expression of nifH. The
      ptsN and ptsA mutants also displayed increased sensitivity to the toxic effects
      of malate and succinate. Growth of both mutants was inhibited by these C4
      dicarboxylates at 20 mM at pH 7.0, while wild-type cells grow normally under
      these conditions. The effect of malate occurred independently of the nitrogen
      source used. Growth inhibition was decreased by lowering the pH of the growth
      medium. These results suggest that ptsN and ptsA are part of the same regulatory
      cascade, the inactivation of which renders the cells sensitive to toxic effects
      of elevated concentrations of malate or succinate.

PMID- 9537370
TI  - Cloning and characterization of the Pseudomonas aeruginosa zwf gene encoding
      glucose-6-phosphate dehydrogenase, an enzyme important in resistance to methyl
      viologen (paraquat).
AB  - In this study, we cloned the Pseudomonas aeruginosa zwf gene, encoding glucose-6
      phosphate dehydrogenase (G6PDH), an enzyme that catalyzes the NAD+- or NADP+
      dependent conversion of glucose-6-phosphate to 6-phosphogluconate. The predicted
      zwf gene product is 490 residues, which could form a tetramer with a molecular
      mass of approximately 220 kDa. G6PDH activity and zwf transcription were maximal
      in early logarithmic phase when inducing substrates such as glycerol, glucose, or
      gluconate were abundant. In contrast, both G6PDH activity and zwf transcription
      plummeted dramatically when bacteria approached stationary phase, when inducing
      substrate was limiting, or when the organisms were grown in a citrate-, succinate
      , or acetate-containing basal salts medium. G6PDH was purified to homogeneity,
      and its molecular mass was estimated to be approximately 220 kDa by size
      exclusion chromatography. Estimated Km values of purified G6PDH acting on glucose
      6-phosphate, NADP+, and NAD+ were 530, 57, and 333 microM, respectively. The
      specific activities with NAD+ and NADP+ were calculated to be 176 and 69
      micromol/min/mg. An isogenic zwf mutant was unable to grow on minimal medium
      supplemented with mannitol. The mutant also demonstrated increased sensitivity to
      the redox-active superoxide-generating agent methyl viologen (paraquat). Since
      one by-product of G6PDH activity is NADPH, the latter data suggest that this
      cofactor is essential for the activity of enzymes critical in defense against
      paraquat toxicity.

PMID- 9537371
TI  - Characterization of the starvation-survival response of Staphylococcus aureus.
AB  - The starvation-survival response of Staphylococcus aureus as a result of glucose,
      amino acid, phosphate, or multiple-nutrient limitation was investigated. Glucose
      and multiple-nutrient limitation resulted in the loss of viability of about 99 to
      99.9% of the population within 2 days. The remaining surviving cells developed
      increased survival potential, remaining viable for months. Amino acid or
      phosphate limitation did not lead to the development of a stable starvation
      survival state, and cells became nonculturable within 7 days. For multiple
      nutrient limitation, the development of the starvation-survival state was cell
      density dependent. Starvation survival was associated with a decrease in cell
      size and increase in resistance to acid shock and oxidative stress. There was no
      evidence for the formation of a viable but nonculturable state during starvation
      as demonstrated by flow cytometry. Long-term survival of cells was dependent on
      cell wall and protein biosynthesis. Analysis of [35S]methionine incorporation and
      labelled proteins demonstrated that differential protein synthesis occurred deep
      into starvation.

PMID- 9537372
TI  - Genetic complementation and kinetic analyses of Rhodobacter capsulatus ORF1696
      mutants indicate that the ORF1696 protein enhances assembly of the light
      harvesting I complex.
AB  - Rhodobacter capsulatus ORF1696 mutant strains were created by insertion of
      antibiotic resistance cartridges at different sites within the ORF1696 gene in a
      strain that lacks the light-harvesting II (LHII) complex. Steady-state absorption
      spectroscopy profiles and the kinetics of the light-harvesting I (LHI) complex
      assembly and decay were used to evaluate the function of the ORF1696 protein in
      various strains. All of the mutant strains were found to be deficient in the LHI
      complex, including one (deltaNae) with a disruption located 13 codons before the
      3' end of the gene. A 5'-proximal disruption after the 31st codon of ORF1696
      resulted in a mutant strain (deltaMun) with a novel absorption spectrum. The two
      strains with more 3' disruptions (deltaStu and deltaNae) were restored nearly to
      the parental strain phenotype when trans complemented with a plasmid expressing
      the ORF1696 gene, but deltaMun was not. The absorption spectrum of deltaMun
      resembled that of a strain which had a polar mutation in ORF1696. We suggest that
      a rho-dependent transcription termination site exists between the MunI and
      proximal StuI sites of ORF1696. A comparison of LHI complex assembly kinetics
      showed that assembly occurred 2.6-fold faster in the parental strain than in
      strain deltaStu. In contrast, LHI complex decay occurred 1.7-fold faster in the
      ORF1696 parental strain than in deltaStu. These results indicate that the ORF1696
      protein has a major effect on LHI complex assembly, and models of ORF1696
      function are proposed.

PMID- 9537373
TI  - Involvement of recF, recO, and recR genes in UV-radiation mutagenesis of
      Escherichia coli.
AB  - The recF, recO, and recR genes were originally identified as those affecting the
      RecF pathway of recombination in Escherichia coli cells. Several lines of
      evidence suggest that the recF, recO, and recR genes function at the same step of
      recombination and postreplication repair. In this work, we report that null
      mutations in recF, recO, or recR greatly reduce UV-radiation mutagenesis (UVM) in
      an assay for reversion from a Trp- (trpE65) to a Trp+ phenotypes. Introduction of
      the defective lexA51 mutation [lexA51(Def)] and/or UmuD' into recF, recO, and
      recR mutants failed to restore normal UVM in the mutants. On the other hand, the
      presence of recA2020, a suppressor mutation for recF, recO, and recR mutations,
      restored normal UVM in recF, recO, and recR mutants. These results indicate an
      involvement of the recF, recO, and recR genes and their products in UVM, possibly
      by affecting the third role of RecA in UVM.

PMID- 9537374
TI  - The TATA-binding protein (TBP) from the human fungal pathogen Candida albicans
      can complement defects in human and yeast TBPs.
AB  - Candida albicans is the major fungal pathogen in humans, yet little is known
      about transcriptional regulation in this organism. Therefore, we have isolated,
      characterized, and expressed the C. albicans TATA-binding protein (TBP) gene
      (TBP1), because this general transcription initiation factor plays a key role in
      the activation and regulation of eukaryotic promoters. Southern and Northern blot
      analyses suggest that a single C. albicans TBP1 locus is expressed at similar
      levels in the yeast and hyphal forms of this fungus. The TBP1 open reading frame
      is 716 bp long and encodes a functional TBP of 27 kDa. C. albicans TBP is capable
      of binding specifically to a TATA box in vitro, substituting for the human TBP to
      activate basal transcription in vitro, and suppressing the lethal delta spt15
      mutation in Saccharomyces cerevisiae. The predicted amino acid sequences of TBPs
      from C. albicans and other organisms reveal a striking pattern of C-terminal
      conservation and N-terminal variability: the C-terminal DNA-binding domain
      displays at least 80% amino acid sequence identity to TBPs from fungi, flies,
      nematodes, slime molds, plants, and humans. Sequence differences between human
      and fungal TPBs in the DNA-binding domain may represent potential targets for
      antifungal therapy.

PMID- 9537375
TI  - Positive and negative transcriptional regulation of the Escherichia coli
      gluconate regulon gene gntT by GntR and the cyclic AMP (cAMP)-cAMP receptor
      protein complex.
AB  - The gntT gene of Escherichia coli is specifically induced by gluconate and
      repressed via catabolite repression. Thus, gluconate is both an inducer and a
      repressor of gntT expression since gluconate is a catabolite-repressing sugar. In
      a gntR deletion mutant, the expression of a chromosomal gntT::lacZ fusion is both
      high and constitutive, confirming that GntR is the negative regulator of gntT.
      Indeed, GntR binds to two consensus gnt operator sites; one overlaps the -10
      region of the gntT promoter, and the other is centered at +120 with respect to
      the transcriptional start site. The binding of GntR to these sites was proven in
      vitro by gel redardation assays and in vivo by site-directed mutagenesis of the
      binding sites. Binding of GntR to the operators is eliminated by gluconate and
      also by 6-phosphogluconate at a 10-fold-higher concentration. Interestingly, when
      gntR deletion strains are grown in the presence of gluconate, there is a twofold
      decrease in gntT expression which is independent of catabolite repression and
      binding of GntR to the operator sites. This novel response of gntR mutants to the
      inducer is termed ultrarepression. Transcription of gntT is activated by binding
      of the cyclic AMP (cAMP)-cAMP receptor protein (CRP) complex to a CRP binding
      site positioned at -71 upstream of the gntT transcription start site.

PMID- 9537376
TI  - Probing the yeast phase-specific expression of the CBP1 gene in Histoplasma
      capsulatum.
AB  - Histoplasma capsulatum is a pathogenic fungus that exists in two distinct forms.
      The saprophytic mycelial phase inhabits moist soil environments; once inhaled,
      hyphae and conidia convert to a unicellular yeast phase that is capable of
      parasitizing macrophage phagolysosomes. Yeasts cultures, but not mycelial
      cultures, release large quantities of a calcium-binding protein (CBP) which may
      be important in calcium acquisition during intracellular parasitism. In this
      study, we show that the gene encoding CBP (CBP1) is transcriptionally regulated.
      To identify promoter sequences that are important for yeast phase-specific
      activity, we created a series of fusions between successively truncated CBP1 5'
      untranslated regulatory sequences and the Escherichia coli lacZ gene. The fusions
      were constructed on a telomeric shuttle plasmid that can replicate autonomously
      in the fungus. By assaying for beta-galactosidase activity from H. capsulatum
      transformants, we identified a 102-bp region that mediates promoter activation
      and yeast phase promoter activity. Base pair substitution analysis suggests that
      the sequences between 839 and 877 bp upstream of the start codon are the most
      important for this positive regulation.

PMID- 9537377
TI  - Identification of a novel Salmonella invasion locus homologous to Shigella ipgDE.
AB  - Genes essential for Salmonella typhimurium invasion have been localized to
      Salmonella pathogenicity island 1 (SPI1) on the chromosome. However, it is clear
      that other genes are required for the invasion process. Mutations that abolish
      the SPI1 invasion type III secretion system do not significantly reduce invasion
      into Chinese hamster ovary tissue culture cells. Two invasion defective mutants
      were isolated by screening 2,500 Tn10dTc insertion mutants of S. typhimurium in
      the tissue culture invasion assay. One of the invasion mutants, SVM167, has an
      insertion between centisomes 24.5 and 25.5 in an operon homologous to the ipgDEF
      operon of the Shigella flexneri and Shigella sonnei virulence plasmid. A second
      mutant, SVM168, has an insertion in an IS3-type element with homology to the
      Salmonella enteritidis IS1351 element and Yersinia enterocolitica IS1400 element
      from a high-pathogenicity island. Further characterization of SVM167 showed that
      culture supernatants from this mutant lack a previously uncharacterized protein
      that is also missing from culture supernatants of a SPI1 mutant, suggesting it
      can be secreted by the SPI1 type III secretion system. In addition, transcription
      of this operon, sigDE (Salmonella invasion gene), is dependent on the presence of
      sirA, an activator of hilA expression. HilA activates transcription of several of
      the SPI1 genes but does not appear to have a major role in activation of
      transcription from the sigDE promoter.

PMID- 9537378
TI  - Promoter characterization and constitutive expression of the Escherichia coli
      gcvR gene.
AB  - The Escherichia coli glycine cleavage repressor protein (GcvR) negatively
      regulates expression of the glycine cleavage operon (gcv). In this study, the
      gcvR translational start site was determined by N-terminal amino acid sequence
      analysis of a GcvR-LacZ fusion protein. Primer extension analysis of the gcvR
      promoter region identified a primary transcription start site 27 bp upstream of
      the UUG translation start site and a minor transcription start site approximately
      100 bp upstream of the translation start codon. The -10 and -35 promoter regions
      upstream of the primary transcription start site were defined by mutational
      analysis. Expression of a gcvR-lacZ fusion was unaltered in the presence of
      glycine or inosine, molecules known to induce or repress expression of gcv,
      respectively. In addition, it was shown that gcvR-lacZ expression is neither
      regulated by the glycine cleavage activator protein (GcvA) nor autogenously
      regulated by GcvR. From DNA sequence analysis, it was predicted that the
      translation start codon of the downstream bcp gene overlaps the gcvR stop codon,
      suggesting that these genes may form an operon. However, a down mutation in the 
      10 promoter region of gcvR had no effect on the expression of a downstream bcp
      lacZ fusion, and primer extension analysis of the bcp promoter region
      demonstrated that bcp has its own promoter within the gcvR coding sequence. These
      results show that gcvR and bcp do not form an operon. Furthermore, the deletion
      of bcp from the chromosome had no effect on gcv-lacZ expression.

PMID- 9537380
TI  - Identification and function of the pdxY gene, which encodes a novel pyridoxal
      kinase involved in the salvage pathway of pyridoxal 5'-phosphate biosynthesis in
      Escherichia coli K-12.
AB  - pdrK encodes a pyridoxine (PN)/pyridoxal (PL)/pyridoxamine (PM) kinase thought to
      function in the salvage pathway of pyridoxal 5'-phosphate (PLP) coenzyme
      biosynthesis. The observation that pdxK null mutants still contain PL kinase
      activity led to the hypothesis that Escherichia coli K-12 contains at least one
      other B6-vitamer kinase. Here we support this hypothesis by identifying the pdxY
      gene (formally, open reading frame f287b) at 36.92 min, which encodes a novel PL
      kinase. PdxY was first identified by its homology to PdxK in searches of the
      complete E. coli genome. Minimal clones of pdxY+ overexpressed PL kinase specific
      activity about 10-fold. We inserted an omega cassette into pdxY and crossed the
      resulting pdxY::omegaKan(r) mutation into the bacterial chromosome of a pdrB
      mutant, in which de novo PLP biosynthesis is blocked. We then determined the
      growth characteristics and PL and PN kinase specific activities in extracts of
      pdxK and pdxY single and double mutants. Significantly, the requirement of the
      pdxB pdxK pdxY triple mutant for PLP was not satisfied by PL and PN, and the
      triple mutant had negligible PL and PN kinase specific activities. Our combined
      results suggest that the PL kinase PdxY and the PN/PL/PM kinase PdxK are the only
      physiologically important B6 vitamer kinases in E. coli and that their function
      is confined to the PLP salvage pathway. Last, we show that pdxY is located
      downstream from pdxH (encoding PNP/PMP oxidase) and essential tyrS (encoding
      aminoacyl-tRNA(Tyr) synthetase) in a multifunctional operon. pdxY is completely
      cotranscribed with tyrS, but about 92% of tyrS transcripts terminate at a
      putative Rho-factor-dependent attenuator located in the tyrS-pdxY intercistronic
      region.

PMID- 9537379
TI  - The methyl group of the N6-methyl-N6-threonylcarbamoyladenosine in tRNA of
      Escherichia coli modestly improves the efficiency of the tRNA.
AB  - tRNA species that read codons starting with adenosine (A) contain N6
      threonylcarbamoyladenosine (t6A) derivatives adjacent to and 3' of the anticodons
      from all organisms. In Escherichia coli there are 12 such tRNA species of which
      two (tRNA(Thr1)GGU and tRNA(Thr3)GGU) have the t6A derivative N6-methyl-N6
      threonylcarbamoyladenosine (m6t6A37). We have isolated a mutant of E. coli that
      lacks the m6t6A37 in these two tRNA(Thr)GGU species. These tRNA species in the
      mutant are likely to have t6A37 instead of m6t6A37. We show that the methyl group
      of m6t6A37 originates from S-adenosyl-L-methionine and that the gene (tsaA) which
      most likely encodes tRNA(m6t6A37)methyltransferase is located at min 4.6 on the
      E. coli chromosomal map. The growth rate of the cell, the polypeptide chain
      elongation rate, and the selection of Thr-tRNA(Thr)GGU to the ribosomal A site
      programmed with either of the cognate codons ACC and ACU were the same for the
      tsaA1 mutant as for the congenic wild-type strain. The expression of the
      threonine operon is regulated by an attenuator which contains in its leader mRNA
      seven ACC codons that are read by these two m6t6A37-containing tRNA(Thr)GGU
      species. We show that the tsaA1 mutation resulted in a twofold derepression of
      this operon, suggesting that the lack of the methyl group of m6t6A37 in
      tRNA(Thr)GGU slightly reduces the efficiency of this tRNA to read cognate codon
      ACC.

PMID- 9537381
TI  - Efficiency of T4 gene 60 translational bypassing.
AB  - Ribosomes translating bacteriophage T4 gene 60 mRNA bypass 50 noncoding
      nucleotides from a takeoff site at codon 46 to a landing site just upstream of
      codon 47. A key signal for efficient bypassing is contained within the nascent
      peptide synthesized prior to takeoff. Here we show that this signal is
      insensitive to the addition of coding information at its N terminus. In addition,
      analysis of amino-terminal fusions, which allow detection of all major products
      synthesized from the gene 60 mRNA, show that 50% of ribosomes bypass the coding
      gap while the rest either terminate at a UAG stop codon immediately following
      codon 46 or fail to resume coding. Bypassing efficiency estimates significantly
      lower than 50% were obtained with enzymatic reporter systems that relied on
      comparing test constructs to constructs with a precise excision of the gap (gap
      deletion). Further analysis showed that these estimates are distorted by
      differences between test and gap deletion functional mRNA levels. An internal
      translation initiation site at Met12 of gene 60 (which eliminates part of the
      essential nascent peptide) also distorts these estimates. Together, these results
      support an efficiency estimate of approximately 50%, less than previously
      reported. This estimate suggests that bypassing efficiency is determined by the
      competition between reading signals and release factors and gives new insight
      into the kinetics of bypassing signal action.

PMID- 9537382
TI  - Acquisition of five high-Mr penicillin-binding protein variants during transfer
      of high-level beta-lactam resistance from Streptococcus mitis to Streptococcus
      pneumoniae.
AB  - Penicillin-resistant isolates of Streptococcus pneumoniae generally contain
      mosaic genes encoding the low-affinity penicillin-binding proteins (PBPs) PBP2x,
      PBP2b, and PBP1a. We now present evidence that PBP2a and PBP1b also appear to be
      low-affinity variants and are encoded by distinct alleles in beta-lactam
      resistant transformants of S. pneumoniae obtained with chromosomal donor DNA from
      a Streptococcus mitis isolate. Different lineages of beta-lactam-resistant
      pneumococcal transformants were analyzed, and transformants with low-affinity
      variants of all high-molecular-mass PBPs, PBP2x, -2a, -2b, -1a, and -1b, were
      isolated. The MICs of benzyl-penicillin, oxacillin, and cefotaxime for these
      transformants were up to 40, 100, and 50 microg/ml, respectively, close to the
      MICs for the S. mitis donor strain. Recruitment of low-affinity PBPs was
      accompanied by a decrease in cross-linked muropeptides as revealed by high
      performance liquid chromatography of muramidase-digested cell walls, but no
      qualitative changes in muropeptide chemistry were detected. The growth rates of
      all transformants were identical to that of the parental S. pneumoniae strain.
      The results stress the potential for the acquisition by S. pneumoniae of high
      level beta-lactam resistance by interspecies gene transfer.

PMID- 9537383
TI  - Novel assay reveals multiple pathways regulating stress-induced accumulations of
      inorganic polyphosphate in Escherichia coli.
AB  - A major impediment to understanding the biological roles of inorganic
      polyphosphate (polyP) has been the lack of sensitive definitive methods to
      extract and quantitate cellular polyP. We show that polyP recovered in extracts
      from cells lysed with guanidinium isothiocynate can be bound to silicate glass
      and quantitatively measured by a two-enzyme assay: polyP is first converted to
      ATP by polyP kinase, and the ATP is hydrolyzed by luciferase to generate light.
      This nonradioactive method can detect picomolar amounts of phosphate residues in
      polyP per milligram of extracted protein. A simplified procedure for preparing
      polyP synthesized by polyP kinase is also described. Using the new assay, we
      found that bacteria subjected to nutritional or osmotic stress in a rich medium
      or to nitrogen exhaustion had large and dynamic accumulations of polyP. By
      contrast, carbon exhaustion, changes in pH, temperature upshifts, and oxidative
      stress had no effect on polyP levels. Analysis of Escherichia coli mutants
      revealed that polyP accumulation depends on several regulatory genes, glnD
      (NtrC), rpoS, relA, and phoB.

PMID- 9537384
TI  - An exported inducer peptide regulates bacteriocin production in Enterococcus
      faecium CTC492.
AB  - Production of the bacteriocins enterocin A and enterocin B in Enterococcus
      faecium CTC492 was dependent on the presence of an extracellular peptide produced
      by the strain itself. This induction factor (EntF) was purified, and amino acid
      sequencing combined with DNA sequencing of the corresponding gene identified it
      as a peptide of 25 amino acids. The gene encodes a prepeptide of 41 amino acids,
      including a 16-amino-acid leader peptide of the double-glycine type.
      Environmental factors influenced the level of bacteriocin production in E.
      faecium CTC492. The optimal pH for bacteriocin production was 6.2. At pH 5.5,
      growth was slow, and very little bacteriocin was formed. The presence of NaCl or
      ethanol (EtOH) was also inhibitory to bacteriocin production, and at high
      concentrations of these solutes, no bacteriocin production was observed. The
      induction factor induced its own synthesis, and by dilution of the culture 106
      times or more, nonproducing cultures were obtained. Bacteriocin production was
      induced in these cultures by addition of EntF. The response was linear, and low
      bacteriocin production could be induced by about 10(-17) M EntF. This response
      was attenuated by low pH or the presence of high concentrations of NaCl or EtOH,
      and 300 times more EntF was needed to induce detectable bacteriocin production in
      the presence of 6.5% NaCl. High levels of bacteriocin production in cultures
      grown at low pH or in the presence of high concentrations of NaCl or EtOH were
      obtained by addition of sufficient amounts of EntF.

PMID- 9537385
TI  - Characterization of a novel member of the DegS-DegU regulon affected by salt
      stress in Bacillus subtilis.
AB  - As a soil bacterium also found in estuarine and marine habitats, Bacillus
      subtilis has evolved various sensing and adaptation systems in order to face salt
      stress conditions. Among these regulatory mechanisms is the DegS-DegU signal
      transduction system, which was previously shown to be stimulated by high salt
      concentrations. A search for promoters regulated in response to salt stress led
      to the identification of wapA, encoding a wall-associated protein, which is
      strongly expressed at low salt concentrations and almost completely repressed in
      the presence of 0.7 M disodium succinate. Repression of wapA transcription by
      salt stress was shown to require the phosphorylated form of DegU. Moreover, DegU
      mediated repression of wapA occurred only in high-salt medium. Alignment between
      the control region of wapA and other DegU-regulated promoters allowed the
      identification of a putative DegU target sequence, AGAAN(11)TTCAG.
      Mutation/deletion analyses of the wapA promoter region confirmed the role of the
      putative DegU control site in repression of wapA transcription at high salt
      concentrations and revealed a second site of repression located downstream from
      the transcription start site. Since residual negative control was observed at
      this second site in the absence of DegU, it seems likely that an additional
      repressor acts on the wapA control region to further downregulate wapA
      transcription under salt stress conditions.

PMID- 9537386
TI  - Chemotactic adaptation is altered by changes in the carboxy-terminal sequence
      conserved among the major methyl-accepting chemoreceptors.
AB  - In Escherichia coli and Salmonella typhimurium, methylation and demethylation of
      receptors are responsible for chemotactic adaptation and are catalyzed by the
      methyltransferase CheR and the methylesterase CheB, respectively. Among the
      chemoreceptors of these species, Tsr, Tar, and Tcp have a well-conserved carboxy
      terminal motif (NWET/SF) that is absent in Trg and Tap. When they are expressed
      as sole chemoreceptors, Tsr, Tar, and Tcp support good adaptation, but Trg and
      Tap are poorly methylated and supported only weak adaptation. It was recently
      discovered that CheR binds to the NWETF sequence of Tsr in vitro. To examine the
      physiological significance of this binding, we characterized mutant receptors in
      which this pentapeptide sequence was altered. C-terminally-mutated Tar and Tcp
      expressed in a receptorless E. coli strain mediated responses to aspartate and
      citrate, respectively, but their adaptation abilities were severely impaired.
      Their expression levels and attractant-sensing abilities were similar to those of
      the wild-type receptors, but the methylation levels of the mutant receptors
      increased only slightly upon addition of attractants. When CheR was overproduced,
      both the adaptation and methylation profiles of the mutant Tar receptor became
      comparable to those of wild-type Tar. Furthermore, overproduction of CheR also
      enhanced adaptive methylation of wild-type Trg, which lacks the NWETF sequence,
      in the absence of any other chemoreceptor. These results suggest that the
      pentapeptide sequence facilitates effective adaptation and methylation by
      recruiting CheR.

PMID- 9537387
TI  - Thioredoxin is an essential protein induced by multiple stresses in Bacillus
      subtilis.
AB  - Thioredoxin, a small, ubiquitous protein which participates in redox reactions
      through the reversible oxidation of its active center dithiol to a disulfide, is
      an essential protein in Bacillus subtilis. A variety of stresses, including heat
      or salt stress or ethanol treatment, strongly enhanced the synthesis of
      thioredoxin in B. subtilis. The stress induction of the monocistronic trxA gene
      encoding thioredoxin occurs at two promoters. The general stress sigma factor,
      sigmaB, was required for the initiation of transcription at the upstream site,
      S(B), and the promoter preceding the downstream start site, S(A), was presumably
      recognized by the vegetative sigma factor, sigmaA. In contrast to the heat
      inducible, sigmaA-dependent promoters preceding the chaperone-encoding operons
      groESL and dnaK, no CIRCE (for controlling inverted repeat of chaperone
      expression) was present in the vicinity of the start site, S(A). The induction
      patterns of the promoters differed, with the upstream promoter displaying the
      typical stress induction of sigmaB-dependent promoters. Transcription initiating
      at S(A), but not at S(B), was also induced after treatment with hydrogen peroxide
      or puromycin. Such a double control of stress induction at two different
      promoters seems to be typical of a subgroup of class III heat shock genes of B.
      subtilis, like clpC, and it either allows the cells to raise the level of the
      antioxidant thioredoxin after oxidative stress or allows stressed cells to
      accumulate thioredoxin. These increased levels of thioredoxin might help stressed
      B. subtilis cells to maintain the native and reduced state of cellular proteins.

PMID- 9537388
TI  - Regulation of ntcA expression and nitrite uptake in the marine Synechococcus sp.
      strain WH 7803.
AB  - NtcA is a transcriptional activator involved in global nitrogen control in
      cyanobacteria. In the absence of ammonium it regulates the transcription of a
      series of genes encoding proteins required for the uptake and assimilation of
      alternative nitrogen sources (I. Luque, E. Flores, and A. Herrero, EMBO J.
      13:2862-2869, 1994). ntcA, present in a single copy in the marine Synechococcus
      sp. strain WH 7803, was cloned and sequenced. The putative amino acid sequence
      shows a high degree of identity to NtcA from freshwater cyanobacteria in two
      functional domains. The expression of ntcA was negatively regulated by ammonium
      from a putative transcription start point located downstream of an NtcA consensus
      recognition sequence. Addition of either rifampin or ammonium led to a rapid
      decline in ntcA transcript levels with half-lives of less than 2 min in both
      cases. Nitrate-grown cells showed high ntcA transcript levels, as well as the
      capacity for active nitrite uptake. However, ammonium-grown cells showed low
      levels of the ntcA transcript and did not utilize nitrite. The addition of
      ammonium to nitrite uptake-active cells resulted in a gradual decline in the rate
      of uptake over a 24-h period. Active nitrite uptake was not induced in cells
      transferred to medium lacking a nitrogen source despite evidence of elevated
      expression of ntcA, indicating that ntcA expression is not sufficient for uptake
      capacity to develop. Nitrate and nitrite addition led to the development of
      nitrite uptake, whereas the addition of leucine did not. Furthermore, nitrite
      addition triggered the de novo protein synthesis required for uptake capacity to
      develop. These data suggest that nitrite and nitrate act as specific inducers for
      the synthesis of proteins required for nitrite uptake.

PMID- 9537389
TI  - A small protein (Ags1p) and the Pho80p-Pho85p kinase complex contribute to
      aminoglycoside antibiotic resistance of the yeast Saccharomyces cerevisiae.
AB  - We identified the AGS1 and AGS3 genes by their ability to partially complement an
      ags mutant (RC1707) which is supersensitive to various aminoglycoside antibiotics
      (J. F. Ernst and R. K. Chan, J. Bacteriol. 163:8-14, 1985). AGS1 is located in
      proximity to the centromere of chromosome III and encodes a small protein of 88
      amino acids. The size of the AGS1 transcript, which in wild-type cells is 1 kb,
      is reduced to 0.75 kb in mutant RC1707. Disruption of AGS1 rendered strains
      supersensitive to hygromycin B and increased their resistance to vanadate. In
      addition, ags1delta strains underglycosylated invertase but had normal
      carboxypeptidase Y glycosylation, suggesting that Ags1p is required for the
      elaboration of outer N-glycosyl chains. AGS3 was found to be identical to PHO80
      (TUP7), which encodes a cyclin activating the Pho85p protein kinase. Deletion of
      either PHO80 or PHO85 led to aminoglycoside supersensitivity; pho80delta
      ags1delta strains showed an enhanced-sensitivity phenotype compared to single
      mutants. pho80 and pho85 mutants were rendered resistant by deletion of PHO4,
      indicating that activation of the Pho4p transcription factor is required for
      increased aminoglycoside sensitivity. Thus, both the Pho80p-Pho85p kinase complex
      (by Pho4p phosphorylation) and a novel component of the N glycosylation pathway
      contribute to basal levels of aminoglycoside resistance in Saccharomyces
      cerevisiae.

PMID- 9537390
TI  - A nine-residue synthetic propeptide enhances secretion efficiency of heterologous
      proteins in Lactococcus lactis.
AB  - Lactococcus lactis, a gram-positive organism widely used in the food industry, is
      a potential candidate for the secretion of biologically useful proteins. We
      examined the secretion efficiency and capacity of L. lactis by using the
      Staphylococcus aureus nuclease (Nuc) as a heterologous model protein. When
      expressed in L. lactis from an efficient lactococcal promoter and its native
      signal peptide, only approximately 60% of total Nuc was present in a secreted
      form at approximately 5 mg per liter. The remaining 40% was found in a cell
      associated precursor form. The secretion efficiency was reduced further to
      approximately 30% by the deletion of 17 residues of the Nuc native propeptide
      (resulting in NucT). We identified a modification which improved secretion
      efficiency of both native Nuc and NucT. A 9-residue synthetic propeptide,
      LEISSTCDA, which adds two negative charges at the +2 and +8 positions, was fused
      immediately after the signal peptide cleavage site. In the case of Nuc, secretion
      efficiency was increased to approximately 80% by LEISSTCDA insertion without
      altering the signal peptide cleavage site, and the yield was increased two- to
      fourfold (up to approximately 20 mg per liter). The improvement of NucT secretion
      efficiency was even more marked and rose from 30 to 90%. Similarly, the secretion
      efficiency of a third protein, the alpha-amylase of Bacillus stearothermophilus,
      was also improved by LEISSTCDA. These data indicate that the LEISSTCDA synthetic
      propeptide improves secretion of different heterologous proteins in L. lactis.

PMID- 9537392
TI  - Sterol uptake in Saccharomyces cerevisiae heme auxotrophic mutants is affected by
      ergosterol and oleate but not by palmitoleate or by sterol esterification.
AB  - The relationship between sterol uptake and heme competence in two yeast strains
      impaired in heme synthesis, namely, G204 and H12-6A, was analyzed. To evaluate
      heme availability, a heterologous 17alpha-hydroxylase cytochrome P-450 cDNA (P
      450c17) was expressed in these strains, and its activity was measured in vivo.
      Heme deficiency in G204 led to accumulation of squalene and lethality. The
      heterologous cytochrome P-450 was inactive in this strain. The leaky H12-6A
      strain presented a slightly modified sterol content compared to that for the wild
      type, and the P-450c17 recovered partial activity. By analyzing sterol transfer
      on nongrowing cells, it was shown that the cells were permeable toward exogenous
      cholesterol when they were depleted of endogenous sterols, which was the case for
      G204 but not for H12-6A. It was concluded that the fully blocked heme mutant
      (G204) replenishes its diminishing endogenous sterol levels during growth by
      replacement with sterol from the outside medium. Endogenous sterol biosynthesis
      appears to be the primary factor capable of excluding exogenous sterol. Oleate
      but not palmitoleate was identified as a component that reduced but did not
      prevent sterol transfer. Sterol transfer was only slightly affected by a lack of
      esterification. It is described herein how avoidance of the potential
      cytotoxicity of the early intermediates of the mevalonate pathway could be
      achieved by a secondary heme mutation in erg auxotrophs.

PMID- 9537391
TI  - An export-specific reporter designed for gram-positive bacteria: application to
      Lactococcus lactis.
AB  - The identification of exported proteins by fusion studies, while well developed
      for gram-negative bacteria, is limited for gram-positive bacteria, in part due to
      drawbacks of available export reporters. In this work, we demonstrate the export
      specificity and use of the Staphylococcus aureus secreted nuclease (Nuc) as a
      reporter for gram-positive bacteria. Nuc devoid of its export signal (called
      delta(SP)Nuc) was used to create two fusions whose locations could be
      differentiated. Nuclease activity was shown to require an extracellular location
      in Lactococcus lactis, thus demonstrating the suitability of delta(SP)Nuc to
      report protein export. The shuttle vector pFUN was designed to construct
      delta(SP)Nuc translational fusions whose expression signals are provided by
      inserted DNA. The capacity of delta(SP)Nuc to reveal and identify exported
      proteins was tested by generating an L. lactis genomic library in pFUN and by
      screening for Nuc activity directly in L. lactis. All delta(SP)Nuc fusions
      displaying a strong Nuc+ phenotype contained a classical or a lipoprotein-type
      signal peptide or single or multiple transmembrane stretches. The function of
      some of the predicted signals was confirmed by cell fractionation studies. The
      fusions analyzed included long (up to 455-amino-acid) segments of the exported
      proteins, all previously unknown in L. lactis. Homology searches indicate that
      several of them may be implicated in different cell surface functions, such as
      nutrient uptake, peptidoglycan assembly, environmental sensing, and protein
      folding. Our results with L. lactis show that delta(SP)Nuc is well suited to
      report both protein export and membrane protein topology.

PMID- 9537393
TI  - The Escherichia coli mrsC gene is required for cell growth and mRNA decay.
AB  - We have identified a gene in Escherichia coli that is required for both the
      normal decay of mRNA and RNA synthesis. Originally designated mrsC (mRNA
      stability), the mrsC505 mutation described here is, in fact, an allele of the
      hflB/ftsH locus (R.-F. Wang et al., J. Bacteriol. 180:1929-1938, 1998). Strains
      carrying the thermosensitive mrsC505 allele stopped growing soon after the
      temperature was shifted to 44 degrees C but remained viable for several hours.
      Net RNA synthesis stopped within 20 min after the shift, while DNA and protein
      synthesis continued for over 60 min. At 44 degrees C, the half-life of total
      pulse-labeled RNA rose from 2.9 min in a wild-type strain to 5.9 min in the
      mrsC505 single mutant. In an rne-1 mrsC505 double mutant, the average half-life
      was 19.8 min. Inactivating mrsC significantly increased the half-lives of the
      trxA, cat, secG, and kan mRNAs, particularly in an mrsC505 pnp-7 rnb-500 rne-1
      multiple mutant. In addition, Northern analysis showed dramatic stabilizations of
      full-length mRNAs in a variety of mrsC505 multiple mutants at 44 degrees C. These
      results suggest that MrsC, directly or indirectly, controls endonucleolytic
      processing of mRNAs that may be independent of the RNase E-PNPase-RhlB
      multiprotein complex.

PMID- 9537395
TI  - Functions encoded by pyrrolnitrin biosynthetic genes from Pseudomonas
      fluorescens.
AB  - Pyrrolnitrin is a secondary metabolite derived from tryptophan and has strong
      antifungal activity. Recently we described four genes, prnABCD, from Pseudomonas
      fluorescens that encode the biosynthesis of pyrrolnitrin. In the work presented
      here, we describe the function of each prn gene product. The four genes encode
      proteins identical in size and serology to proteins present in wild-type
      Pseudomonas fluorescens, but absent from a mutant from which the entire prn gene
      region had been deleted. The prnA gene product catalyzes the chlorination of L
      tryptophan to form 7-chloro-L-tryptophan. The prnB gene product catalyzes a ring
      rearrangement and decarboxylation to convert 7-chloro-L-tryptophan to
      monodechloroaminopyrrolnitrin. The prnC gene product chlorinates
      monodechloroaminopyrrolnitrin at the 3 position to form aminopyrrolnitrin. The
      prnD gene product catalyzes the oxidation of the amino group of aminopyrrolnitrin
      to a nitro group to form pyrrolnitrin. The organization of the prn genes in the
      operon is identical to the order of the reactions in the biosynthetic pathway.

PMID- 9537394
TI  - Escherichia coli mrsC is an allele of hflB, encoding a membrane-associated ATPase
      and protease that is required for mRNA decay.
AB  - The mrsC gene of Escherichia coli is required for mRNA turnover and cell growth,
      and strains containing the temperature-sensitive mrsC505 allele have longer half
      lives than wild-type controls for total pulse-labeled and individual mRNAs (L. L.
      Granger et al., J. Bacteriol. 180:1920-1928, 1998). The cloned mrsC gene contains
      a long open reading frame beginning at an initiator UUG codon, confirmed by N
      terminal amino acid sequencing, encoding a 70,996-Da protein with a consensus ATP
      binding domain. mrsC is identical to the independently identified ftsH gene
      except for three additional amino acids at the N terminus (T. Tomoyasu et al., J.
      Bacteriol. 175:1344-1351, 1993). The purified protein had a Km of 28 microM for
      ATP and a Vmax of 21.2 nmol/microg/min. An amino-terminal glutathione S
      transferase-MrsC fusion protein retained ATPase activity but was not biologically
      active. A glutamic acid replacement of the highly conserved lysine within the ATP
      binding motif (mrsC201) abolished the complementation of the mrsC505 mutation,
      confirming that the ATPase activity is required for MrsC function in vivo. In
      addition, the mrsC505 allele conferred a temperature-sensitive HflB phenotype,
      while the hflB29 mutation promoted mRNA stability at both 30 and 44 degrees C,
      suggesting that the inviability associated with the mrsC505 allele is not related
      to the defect in mRNA decay. The data presented provide the first direct evidence
      for the involvement of a membrane-bound protein in mRNA decay in E. coli.

PMID- 9537396
TI  - Levels of the Vsr endonuclease do not regulate stationary-phase reversion of a
      Lac- frameshift allele in Escherichia coli.
AB  - Vsr endonuclease, which initiates very short patch repair, has been hypothesized
      to regulate mutation in stationary-phase cells. Overexpression of Vsr does
      dramatically increase the stationary-phase reversion of a Lac- frameshift allele,
      but the absence of Vsr has no effect. Thus, at least in this case, Vsr has no
      regulatory role in stationary-phase mutation, and the effects of Vsr
      overproduction are likely to be artifactual.

PMID- 9537397
TI  - The active-site cysteines of the periplasmic thioredoxin-like protein CcmG of
      Escherichia coli are important but not essential for cytochrome c maturation in
      vivo.
AB  - A new member of the family of periplasmic protein thiol:disulfide
      oxidoreductases, CcmG (also called DsbE), was characterized with regard to its
      role in cytochrome c maturation in Escherichia coli. The CcmG protein was shown
      to be membrane bound, facing the periplasm with its C-terminal, hydrophilic
      domain. A chromosomal, nonpolar in-frame deletion in ccmG resulted in the
      complete absence of all c-type cytochromes. Replacement of either one or both of
      the two cysteine residues of the predicted active site in CcmG (WCPTC) led to low
      but detectable levels of Bradyrhizobium japonicum holocytochrome c550 expressed
      in E. coli. This defect, but not that of the ccmG null mutant, could be
      complemented by adding low-molecular-weight thiol compounds to growing cells,
      which is in agreement with a reducing function for CcmG.

PMID- 9537398
TI  - The atrazine catabolism genes atzABC are widespread and highly conserved.
AB  - Pseudomonas strain ADP metabolizes the herbicide atrazine via three enzymatic
      steps, encoded by the genes atzABC, to yield cyanuric acid, a nitrogen source for
      many bacteria. Here, we show that five geographically distinct atrazine-degrading
      bacteria contain genes homologous to atzA, -B, and -C. The sequence identities of
      the atz genes from different atrazine-degrading bacteria were greater than 99% in
      all pairwise comparisons. This differs from bacterial genes involved in the
      catabolism of other chlorinated compounds, for which the average sequence
      identity in pairwise comparisons of the known members of a class ranged from 25
      to 56%. Our results indicate that globally distributed atrazine-catabolic genes
      are highly conserved in diverse genera of bacteria.

PMID- 9537399
TI  - Frequency of pilin antigenic variation in Neisseria gonorrhoeae.
AB  - Variation of the pilus of Neisseria gonorrhoeae occurs by the recombination of
      silent pilin DNA sequences into the pilin expression locus. We have developed a
      quantitative, competitive reverse transcription-PCR assay which measures the
      frequency of pilin antigenic variation independently of changes in gonococcal
      colony morphology and have determined this frequency within a gonococcal
      population. We have also studied the frequency of antigenic variation during
      growth and have concluded that growth does not dramatically influence the
      frequency of pilin antigenic variation, although a reproducible, twofold increase
      is observed upon the transition into late log/stationary phase.

PMID- 9537400
TI  - Occurrence of homologs of the Escherichia coli lytB gene in gram-negative
      bacterial species.
AB  - The Escherichia coli LytB protein regulates the activity of guanosine 3',5'
      bispyrophosphate synthetase I (RelA). A Southern blot analysis of chromosomal DNA
      with the E. coli lytB gene as a probe revealed the presence of lytB homologs in
      all of the gram-negative bacterial species examined but not in gram-positive
      species. The lytB homologs from Enterobacter aerogenes and Pseudomonas
      fluorescens complemented the E. coli lytB44 mutant allele.

PMID- 9537401
TI  - Proton gradient-driven nickel uptake by vacuolar membrane vesicles of
      Saccharomyces cerevisiae.
AB  - A vacuolar H+-ATPase-negative mutant of Saccharomyces cerevisiae was highly
      sensitive to nickel ion. Accumulation of nickel ion in the cells of this mutant
      of less than 60% of the value for the parent strain arrested growth, suggesting a
      role for this ATPase in sequestering nickel ion into vacuoles. An artificially
      imposed pH gradient (interior acid) induced transient nickel ion uptake by
      vacuolar membrane vesicles, which was inhibited by collapse of the pH difference
      but not of the membrane potential. Nickel ion transport into vacuoles in a pH
      gradient-dependent manner is thus important for its detoxification in yeast.

PMID- 9537402
TI  - Evidence for a regulatory link of nitrogen fixation and photosynthesis in
      Rhodobacter capsulatus via HvrA.
AB  - A Rhodobacter capsulatus reporter strain, carrying a constitutively expressed
      nifA gene and a nifH-lacZ gene fusion, was used for random transposon Tn5
      mutagenesis to search for genes required for the NtrC-independent ammonium
      repression of NifA activity. A mutation in hvrA, which is known to be involved in
      low-light activation of the photosynthetic apparatus, released both ammonium and
      oxygen control of nifH expression in this reporter strain, demonstrating a
      regulatory link of nitrogen fixation and photosynthesis via HvrA. In addition, a
      significant increase in bacteriochlorophyll alpha (BChl alpha) content was found
      in cells under nitrogen-fixing conditions. HvrA was not involved in this up
      regulation of BChl alpha. Instead, the presence of active nitrogenase seemed to
      be sufficient for this process, since no increase in BChl alpha content was
      observed in different nif mutants.

PMID- 9537403
TI  - Growth rate-dependent accumulation of RNA from plasmid-borne rRNA operons in
      Escherichia coli.
AB  - Inadequate regulation of the expression of additional plasmid-borne rRNA operons
      in Escherichia coli was exaggerated at slow growth rates, resulting in increases
      of approximately 100% for RNA concentration and 33% for doubling time. These
      observations are consistent with the hypothesis that multiple rRNA operons
      constitute a metabolic burden at slow growth rates.

PMID- 9537405
TI  - Building a global mouse house.

PMID- 9537404
TI  - Characterization of the Aspergillus nidulans nmrA gene involved in nitrogen
      metabolite repression.
AB  - The gene nmrA of Aspergillus nidulans has been isolated and found to be a homolog
      of the Neurospora crassa gene nmr-1, involved in nitrogen metabolite repression.
      Deletion of nmrA results in partial derepression of activities subject to
      nitrogen repression similar to phenotypes observed for certain mutations in the
      positively acting areA gene.

PMID- 9537406
TI  - Exploding vertebrate genomes.

PMID- 9537407
TI  - Anti-phosphatases take the stage.

PMID- 9537409
TI  - Human genome diversity--a project?

PMID- 9537408
TI  - Have you used an adeno vector...lately?

PMID- 9537410
TI  - De novo mutations in the CRX homeobox gene associated with Leber congenital
      amaurosis.

PMID- 9537411
TI  - Predicting functions from protein sequences--where are the bottlenecks?
AB  - The exponential growth of sequence data does not necessarily lead to an increase
      in knowledge about the functions of genes and their products. Prediction of
      function using comparative sequence analysis is extremely powerful but, if not
      performed appropriately, may also lead to the creation and propagation of
      assignment errors. While current homology detection methods can cope with the
      data flow, the identification, verification and annotation of functional features
      need to be drastically improved.

PMID- 9537412
TI  - A novel gene encoding an integral membrane protein is mutated in nephropathic
      cystinosis.
AB  - Nephropathic cystinosis, an autosomal recessive disorder resulting from defective
      lysosomal transport of cystine, is the most common inherited cause of renal
      Fanconi syndrome. The cystinosis gene has been mapped to chromosome 17p13. We
      found that the locus D17S829 was homozygously deleted in 23 out of 70 patients,
      and identified a novel gene, CTNS, which mapped to the deletion interval. CTNS
      encodes an integral membrane protein, cystinosin, with features of a lysosomal
      membrane protein. Eleven different mutations, all predicted to cause loss of
      function of the protein, were found to segregate with the disorder.

PMID- 9537413
TI  - Human gene targeting by viral vectors.
AB  - Stable transduction of mammalian cells typically involves random integration of
      viral vectors by non-homologous recombination. Here we report that vectors based
      on adeno-associated virus (AAV) can efficiently modify homologous human
      chromosomal target sequences. Both integrated neomycin phosphotransferase genes
      and the hypoxanthine phosphoribosyltransferase gene were targeted by AAV vectors.
      Site-specific genetic modifications could be introduced into approximately 1% of
      cells, with the highest targeting rates occurring in normal human fibroblasts.
      These results suggest that AAV vectors could be used to introduce specific
      genetic changes into the genomic DNA of a wide variety of mammalian cells,
      including therapeutic gene targeting applications.

PMID- 9537414
TI  - Association of SET domain and myotubularin-related proteins modulates growth
      control.
AB  - Several proteins that contribute to epigenetic mechanisms of gene regulation
      contain a characteristic motif of unknown function called the SET (Suvar3-9,
      Enhancer-of-zeste, Trithorax) domain. We have demonstrated that SET domains
      mediate highly conserved interactions with a specific family of proteins that
      display similarity with dual-specificity phosphatases (dsPTPases). These include
      myotubularin, the gene of which is mutated in a subset of patients with X-linked
      myotubular myopathy, and Sbf1, a newly isolated homologue of myotubularin. In
      contrast with myotubularin, Sbf1 lacks a functional catalytic domain which
      dephosphorylates phospho-tyrosine and serine-containing peptides in vitro.
      Competitive interference of endogenous SET domain-dsPTPase interactions by forced
      expression of Sbf1 induced oncogenic transformation of NIH 3T3 fibroblasts and
      impaired the in vitro differentiation of C2 myoblast cells. We conclude that
      myotubularin-type phosphatases link SET-domain containing components of the
      epigenetic regulatory machinery with signalling pathways involved in growth and
      differentiation.

PMID- 9537415
TI  - A microsatellite genetic linkage map for zebrafish (Danio rerio).
AB  - We have constructed a zebrafish genetic linkage map consisting of 705 simple
      sequence-length polymorphism markers (SSLPs). The map covers 2350 centimorgans
      (cM) of the zebrafish genome with an average resolution of 3.3 cM. It is a
      complete map in genetic mapping terms (there is one linkage group for each of the
      25 chromosomes), and it has been confirmed by somatic-cell hybrids and centromere
      mapping using half-tetrad analysis. The markers are highly polymorphic in the
      zebrafish strains used for genetic crosses and provide a means to compare genetic
      segregation of developmental mutations between laboratories. These markers will
      provide an initial infrastructure for the positional cloning of the nearly 600
      zebrafish genes identified as crucial to vertebrate development,and will become
      the anchor for the physical map of the zebrafish genome.

PMID- 9537417
TI  - A tRNA suppressor mutation in human mitochondria.
AB  - Mitochondrial mutations are associated with a wide spectrum of human diseases. A
      common class of point mutations affects tRNA genes, and mutations in the tRNA
      leu(UUR) gene (MTTL1) are the most frequently detected. In earlier studies, we
      showed that lung carcinoma cybrid cells containing high levels (greater than 95%)
      of mutated mtDNA from a patient with the pathological nucleotide pair (np) 3243
      tRNA-leu(UUR) mutation can remain genotypically stable over time, and exhibit
      severe defects in mitochondrial respiratory metabolism. From such a cybrid
      containing 99% mutated mtDNA, we have isolated a spontaneous derivative that
      retains mutant mtDNA at this level but which has nevertheless reverted to the
      wild-type phenotype, based on studies of respiration, growth in selective media,
      mitochondrial protein synthesis and biogenesis of mitochondrial membrane
      complexes. The cells are heteroplasmic for a novel anticodon mutation in tRNA
      leu(CUN) at np 12300, predicted to generate a suppressor tRNA capable of decoding
      UUR leucine codons. The suppressor mutation represents approximately 10% of the
      total mtDNA, but was undetectable in a muscle biopsy sample taken from the
      original patient or in the parental cybrid. These results indicate that the
      primary biochemical defect in cells with high levels of np 3243 mutated mtDNA is
      the inability to translate UUR leucine codons.

PMID- 9537416
TI  - Vertebrate genome evolution and the zebrafish gene map.
AB  - In chordate phylogeny, changes in the nervous system, jaws, and appendages
      transformed meek filter feeders into fearsome predators. Gene duplication is
      thought to promote such innovation. Vertebrate ancestors probably had single
      copies of genes now found in multiple copies in vertebrates and gene maps suggest
      that this occurred by polyploidization. It has been suggested that one genome
      duplication event occurred before, and one after the divergence of ray-finned and
      lobe-finned fishes. Holland et al., however, have argued that because various
      vertebrates have several HOX clusters, two rounds of duplication occurred before
      the origin of jawed fishes. Such gene-number data, however, do not distinguish
      between tandem duplications and polyploidization events, nor whether independent
      duplications occurred in different lineages. To investigate these matters, we
      mapped 144 zebrafish genes and compared the resulting map with mammalian maps.
      Comparison revealed large conserved chromosome segments. Because duplicated
      chromosome segments in zebrafish often correspond with specific chromosome
      segments in mammals, it is likely that two polyploidization events occurred prior
      to the divergence of fish and mammal lineages. This zebrafish gene map will
      facilitate molecular identification of mutated zebrafish genes, which can suggest
      functions for human genes known only by sequence.

PMID- 9537418
TI  - Neurofibromatosis 2 tumour suppressor schwannomin interacts with betaII-spectrin.
AB  - NF2 is the most commonly mutated gene in benign tumours of the human nervous
      system. The NF2 protein, called schwannomin or merlin, is absent in virtually all
      schwannomas, and many meningiomas and ependymomas. Using the yeast two-hybrid
      system, we identified betaII-spectrin (also known as fodrin) as a schwannomin
      binding protein. Interaction occurred between the carboxy-terminal domain of
      schwannomin isoform 2 and the ankyrin-binding region of betaII-spectrin. Isoform
      1 of schwannomin, in contrast, interacted weakly with betaII-spectrin, presumably
      because of its strong self-interaction. Thus, alternative splicing of NF2 may
      regulate betaII-spectrin binding. Schwannomin co-immunoprecipitated with betaII
      spectrin at physiological concentrations. The two proteins interacted in vitro
      and co-localized in several target tissues and in STS26T cells. Three naturally
      occurring NF2 missense mutations showed reduced, but not absent, betaII-spectrin
      binding, suggesting an explanation for the milder phenotypes seen in patients
      with missense mutations. STS26T cells treated with NF2 antisense oligonucleotides
      showed alterations of the actin cytoskeleton. Schwannomin itself lacks the actin
      binding sites found in ezrin, radixin and moesin, suggesting that signalling to
      the actin cytoskeleton occurs via actin-binding sites on betaII-spectrin. Thus,
      schwannomin is a tumour suppressor directly involved in actin-cytoskeleton
      organization, which suggests that alterations in the cytoskeleton are an early
      event in the pathogenesis of some tumour types.

PMID- 9537419
TI  - Loss of E2F-1 reduces tumorigenesis and extends the lifespan of Rb1(+/-)mice.
AB  - Mutation of the retinoblastoma tumour-suppressor gene (RB) leads to the
      deregulation of many proteins and transcription factors that interact with the
      retinoblastoma gene product (pRB), including members of the E2F transcription
      factor family. As pRB is known to repress E2F transcriptional activity and
      overexpression of E2F is sufficient for cell cycle progression, it is thought
      that pRB suppresses growth in part by repressing E2F-mediated transcription.
      Previously, we reported that loss of E2f1 in mice results in tissue-specific
      tumour induction and tissue atrophy, demonstrating that E2F-1 normally controls
      growth both positively and negatively in a tissue-specific fashion. To determine
      whether E2F-1 deregulation--as a result of loss of pRB--promotes proliferation in
      vivo, we have tested whether loss of E2f1 interferes with the pituitary and
      thyroid tumorigenesis that occurs in Rb1(+/-) mice. We have found that loss of
      E2f1 reduces the frequency of pituitary and thyroid tumours, and greatly
      lengthens the lifespan of Rb1(+/-); E2f1(-/-) animals, demonstrating that E2F-1
      is an important downstream target of pRB during tumorigenesis. Furthermore, loss
      of E2f1 reduces a previously reported strain-dependent difference in Rb1(+/-)
      lifespan, suggesting that E2f1 or an E2F-1-regulated gene acts as a genetic
      modifier between the 129/Sv and C57BL/6 strains.

PMID- 9537420
TI  - Mutations in the caveolin-3 gene cause autosomal dominant limb-girdle muscular
      dystrophy.
AB  - Limb-girdle muscular dystrophy (LGMD) is a clinically and genetically
      heterogeneous group of myopathies, including autosomal dominant and recessive
      forms. To date, two autosomal dominant forms have been recognized: LGMD1A, linked
      to chromosome 5q, and LGMD1B, associated with cardiac defects and linked to
      chromosome 1q11-21. Here we describe eight patients from two different families
      with a new form of autosomal dominant LGMD, which we propose to call LGMD1C,
      associated with a severe deficiency of caveolin-3 in muscle fibres. Caveolin-3
      (or M-caveolin) is the muscle-specific form of the caveolin protein family, which
      also includes caveolin-1 and -2. Caveolins are the principal protein components
      of caveolae (50-100 nm invaginations found in most cell types) which represent
      appendages or sub-compartments of plasma membranes. We localized the human
      caveolin-3 gene (CAV3) to chromosome 3p25 and identified two mutations in the
      gene: a missense mutation in the membrane-spanning region and a micro-deletion in
      the scaffolding domain. These mutations may interfere with caveolin-3
      oligomerization and disrupt caveolae formation at the muscle cell plasma
      membrane.

PMID- 9537421
TI  - Linkage of familial combined hyperlipidaemia to chromosome 1q21-q23.
AB  - More than half of the patients with angiographically confirmed premature coronary
      heart disease (CHD) have a familial lipoprotein disorder. Familial combined
      hyperlipidaemia (FCHL) represents the most common genetic dyslipidemia with a
      prevalence of 1.0-2.0%. FCHL is estimated to cause 10-20% of premature CHD and is
      characterized by elevated levels of cholesterol, triglycerides, or both. Attempts
      to characterize genes predisposing to FCHL have been hampered by its equivocal
      phenotype definition, unknown mode of inheritance and genetic heterogeneity. In
      order to minimize genetic heterogeneity, we chose 31 extended FCHL families from
      the isolated Finnish population that fulfilled strictly defined criteria for the
      phenotype status. We performed linkage analyses with markers from ten chromosomal
      regions that contain lipid-metabolism candidate genes. One marker, D1S104,
      adjacent to the apolipoprotein A-II (APOA2) gene on chromosome 1, revealed a lod
      score of Z = 3.50 assuming a dominant mode of inheritance. Multipoint analysis
      combining information from D1S104 and the neighbouring marker D1S1677 resulted in
      a lod score of 5.93. Physical positioning of known genes in the area (APOA2 and
      three selectin genes) outside the linked region suggests a novel locus for FCHL
      on 1q21-q23. A second paper in this issue (Castellani et al.) reports the
      identification of a mouse combined hyperlipidaemia locus in the syntenic region
      of the mouse genome, thus further implicating a gene in this region in the
      aetiology of FCHL.

PMID- 9537422
TI  - Mapping a gene for combined hyperlipidaemia in a mutant mouse strain.
AB  - Familial combined hyperlipidaemia (FCHL) is a common, multifactorial disorder
      associated with elevated levels of plasma triglyceride, cholesterol, or both. A
      characteristic feature is increased secretion of very low density lipoproteins
      (VLDL) and apolipoprotein B (apoB). Although FCHL is the most common cause of
      premature coronary artery disease (CAD), accounting for over 10% of cases, its
      aetiology remains largely unknown. One powerful approach to the dissection of
      complex genetic traits involves the use of animal models. We have identified a
      mouse strain, HcB-19/Dem (HcB-19), which exhibits hypertriglyceridaemia,
      hypercholesterolaemia and elevated levels of plasma apoB. Like FCHL patients, HcB
      19 mice also exhibit increased secretion of triglyceride-rich lipoproteins, and
      their hyperlipidaemia becomes progressively more severe with age. It is likely
      that the hyperlipidaemia results from a mutation of a novel gene that arose
      during development of strain HcB-19. We mapped the hyperlipidaemia gene (Hyplip1)
      to the distal portion of mouse chromosome 3. This region is syntenic to human
      chromosome 1q21-q23, which has recently been shown to harbour a gene associated
      with FCHL in families from a Finnish isolate.

PMID- 9537423
TI  - Ribozyme-mediated trans-splicing of a trinucleotide repeat.
AB  - Trinucleotide repeat expansions (TREs) are a recently described class of
      mutations characterized by a change in the size of the genomic fragment due to
      amplification of the repeated unit. A number of diseases have been attributed to
      TRE, including Huntington disease and myotonic dystrophy (DM), but attempts at
      genetic therapy have yet to prove successful. A potential therapeutic approach
      would be to repair the expanded repeat using the trans-splicing ability of group
      I intron ribozymes. We have used DM as a model to test this hypothesis. A group I
      intron ribozyme (DMPK-RZ1) was designed to modify the TRE at the 3' end of the
      human myotonic dystrophy protein kinase (DMPK) transcripts. DMPK-RZ1 was shown to
      ligate a small DMPK mRNA fragment, contained within the ribozyme, to a simple
      DMPK-target RNA in vitro. It also modified a larger target transcript, leading to
      replacement of twelve repeats with five repeats, both in vitro and in mammalian
      cells. Finally, this ribozyme successfully replaced the 3' end of endogenous DMPK
      mRNA in fibroblasts with a different 3' region. Ribozyme-mediated RNA repair may
      thus form a novel therapeutic strategy for diseases associated with repeat
      expansions.

PMID- 9537424
TI  - Mutations in the early growth response 2 (EGR2) gene are associated with
      hereditary myelinopathies.
AB  - The early growth response 2 gene (EGR2) is part of a multigene family encoding
      Cys2His2 type zinc-finger proteins and may play a role in the regulation of
      cellular proliferation. Egr2, (also known as Krox20) is the mouse orthologue of
      human EGR2 and was first identified as an immediate-early response gene, encoding
      a protein that binds DNA in a sequence-specific manner and acts as a
      transcription factor. Stable expression of Egr2 is specifically associated with
      the onset of myelination in the peripheral nervous system (PNS). Egr2(-/-) mice
      display disrupted hindbrain segmentation and development, and a block of Schwann
      cell differentiation at an early stage. We hypothesized that Egr2 may be a
      transcription factor affecting late myelin genes and that human myelinopathies of
      the PNS may result from mutations in EGR2. In support of this hypothesis, we have
      identified one recessive and two dominant missense mutations in EGR2 (within
      regions encoding conserved functional domains) in patients with congenital
      hypomyelinating neuropathy (CHN) and a family with Charcot-Marie-Tooth type 1
      (CMT1).

PMID- 9537425
TI  - Chimaeric analysis reveals role of Pdgf receptors in all muscle lineages.
AB  - Blood vessels originate as simple endothelial cell tubes. It has been proposed
      that platelet-derived growth factor B polypeptide (Pdgfb) secreted by these
      endothelial cells drives the formation of the surrounding muscular wall by
      recruiting nearby mesenchymal cells. However, targetted inactivation of the Pdgfb
      gene or the Pdgf receptor beta (Pdgfrb) gene, by homologous recombination, does
      not prevent the development of apparently normal large arteries and connective
      tissue. We have used an in vivo competition assay in which we prepared chimaeric
      blastocysts, composed of a mixture of wild-type (Pdgfrb[+/+]) and Pdgfrb(+/-) or
      wild-type and Pdgfrb(-/-) cells, and quantified the relative success of cells of
      the two component genotypes in competing for representation in different cell
      lineages as the chimaeric embryos developed. This study revealed that the
      participation of Pdgfrb(-/-) cells in all muscle lineages (smooth, cardiac,
      skeletal and pericyte) was reduced by eightfold compared with Pdgfrb(+/+) cells,
      and that participation of Pdgfrb(+/-) cells was reduced by twofold (eightfold for
      pericytes). Pdgfrb inactivation did not affect cell contribution to non-muscle
      mesodermal lineages, including fibroblasts and endothelial cells. Chimaera
      competition is therefore a sensitive, quantitative method for determining
      developmental roles of specific genes, even when those roles are not apparent
      from analysis of purebred mutants; most likely because they are masked by
      homeostatic mechanisms.

PMID- 9537426
TI  - Anatomy of the human biliary system studied by quantitative computer-aided three
      dimensional imaging techniques.
AB  - The branching geometry of the normal, cholangiographically identifiable human
      biliary tree was studied with an innovative computer-aided three-dimensional (3D)
      imaging technique. In addition, a serially sectioned conventional paraffin block
      from a normal donor liver was used to create and quantitatively study a
      microscopic 3D image. Finally, a geometric model was developed to estimate the
      enlargement of biliary surfaces imparted by microvilli. The images created by
      these techniques could be viewed in stationary modes or rotating around any
      preselected axis. Approximately 7 (+/-3) intrahepatic duct orders were
      cholangiographically identified. Computerized measurements of the images from
      three normal livers suggested that the mean total volume of duct orders 1 to 7
      shown in the cholangiograms was 16.6 cm3. The volume of the entire macroscopic
      duct system was estimated to be between 14 and 24 cm3 (mean, 20.4 cm3), with an
      internal surface of 336 to 575 cm2 (mean, 398 cm2). A geometric model based on
      electron micrographs suggested that this surface is magnified approximately 5.5
      fold by the presence of microvilli. Volume and surface area (SA) measurements of
      all ducts in the same orders increased nearly exponentially from the first toward
      the seventh branching order (i.e., from the hilus toward the periphery of the
      liver), and probably beyond. The microscopic computerized reconstruction of a
      septal bile duct with its tributaries also allowed volume measurements; the
      imaged duct system represented 2.7% of the portal tract volume. The data
      presented herein may help to better evaluate branching patterns of the biliary
      tree and, eventually, the quantitative aspects of site-restricted cholangiocyte
      function and their role in the development of biliary diseases.

PMID- 9537427
TI  - Tumor necrosis factor alpha regulates nitric oxide synthase expression in portal
      hypertensive gastric mucosa of rats.
AB  - Anti-tumor necrosis factor alpha (TNF-alpha) treatment decreases nitric oxide
      (NO) synthesis and ameliorates the hyperdynamic circulation in portal
      hypertensive rats. We have recently demonstrated that nitric oxide synthase
      isoform 3 (NOS3) is overexpressed in portal hypertensive gastric mucosa and that
      resultant NO overproduction probably is responsible for the increased
      susceptibility of the mucosa to damage. In the present study, we examined whether
      TNF-alpha is overexpressed in portal hypertensive gastric mucosa and whether anti
      TNF-alpha treatment affects gastric NOS3 messenger RNA (mRNA) and protein
      expression. We examined plasma concentrations of TNF-alpha and its protein
      expression in gastric specimens from portal hypertensive and sham-operated rats
      using Western blotting and immunohistochemistry. We also measured gastric mucosal
      blood flow, gastric expression of NOS3 mRNA and protein, and NOS3 enzyme activity
      in rats with and without TNF-alpha-neutralizing antibody treatment. The TNF-alpha
      protein levels in portal hypertensive stomachs were significantly increased by
      57% compared with levels in sham-operated controls. TNF-alpha antibody treatment
      normalized gastric mucosal blood flow in portal hypertensive stomachs and
      significantly reversed overexpression of gastric NOS3 mRNA, protein, and its
      enzyme activity in portal hypertensive rats by 48%, 45%, and 33%, respectively.
      These results suggest that TNF-alpha may regulate NOS3 expression in the portal
      hypertensive stomach and that anti-TNF-alpha treatment may ameliorate the
      pathophysiological abnormalities of portal hypertensive gastric mucosa.

PMID- 9537428
TI  - Independent and combined action of hepatitis C virus infection and alcohol
      consumption on the risk of symptomatic liver cirrhosis.
AB  - Although alcohol intake and hepatitis C virus (HCV) infection are the major
      determinants of liver cirrhosis (LC) in Western countries, the joint effect of
      these two factors on LC risk has not yet been adequately studied. We used data
      from two hospital-based case-control studies performed in Italy. Cases were 285
      cirrhotic patients admitted for the first time to district hospitals for liver
      decompensation. Controls were 417 patients admitted during the same period, and
      in the same hospitals as the cases, for acute diseases unrelated to alcohol.
      Alcohol consumption was expressed as lifetime daily alcohol intake (LDAI). Serum
      HCV antibodies (anti-HCV) were detected using a second-generation test and
      recombinant immunoblotting assay. We found a dose-effect relationship between
      LDAI and the risk of LC in both anti-HCV-negative and -positive subjects.
      Considering the extreme LDAI categories (LDAI = 0 g, lifetime teetotalers, and
      LDAI = 175 g), the LC odds ratios increased from 1.0 (reference category) to 15.0
      (95% CI, 7.1-31.7) and from 9.2 (95% CI, 2.0-43.2) to 147.2 (95% CI, 42.1-514.3)
      in anti-HCV-negative and -positive patients respectively. The interaction between
      LDAI and HCV showed an additive structure for LDAI < 50 g/day and a
      multiplicative structure for consumption > 125 g/day. Alcohol intake and HCV
      infection are independent risk factors for symptomatic liver cirrhosis, each
      being sufficient to induce the disease. In subjects with high alcohol intake, the
      coexistence of HCV infection multiplies the alcohol-associated risk of cirrhosis.
      In subjects with low alcohol intake, other factors could be involved.

PMID- 9537429
TI  - Hemodynamic effects of the somatostatin analog lanreotide in humans: placebo
      controlled, cross-over dose-ranging Echo-Doppler study.
AB  - Because of their vasoactive effects, somatostatin and its analogs are
      increasingly used in the management of complications of chronic liver diseases
      such as variceal bleeding. Postprandial hyperemia augments splanchnic blood flow,
      subsequently increasing portal pressure. The aim of this study was to explore
      effects of the somatostatin analog, lanreotide, on food-stimulated hemodynamic
      parameters in healthy human subjects. A dose-response curve was constructed in
      eight healthy male subjects in a placebo-controlled cross-over study. On 4
      different days, either 0 (placebo), 50, 100, or 200 microg/h of lanreotide was
      infused intravenously in random order, starting at 45 minutes for 7 hours. On
      each day, a liquid test meal (Ensure plus, 1.5 kcal/mL) was perfused
      intraduodenally at a rate of 3 mL/min over 7 hours after a 45-minute basal
      period. Diastolic arterial pressure (dBP), heart rate (HR), superior mesenteric
      arterial (SMA) average flow velocity (SMA-V), SMA pulsatility index (SMA-PI),
      portal venous volume flow (PV-F), and renal artery (RA) resistance index (RA-RI)
      were measured on regular intervals (flows using Echo-Doppler technology).
      Lanreotide at all doses abolished food-stimulated splanchnic hyperemia both in
      the SMA and PV over 7 hours. The fall in dBP and increase in HR after food
      perfusion were blunted under lanreotide. Food as well as lanreotide did not
      modify RA-RI. In summary: 1) lanreotide inhibits food-induced splanchnic
      hyperemia in normal subjects; 2) in parallel, systemic hemodynamic alterations to
      food stimulation are abolished with lanreotide; and 3) renal vascular resistance
      is unchanged. Because of its persistent splanchnic vasoconstrictive effect,
      lanreotide should be tested in patients with portal hypertension.

PMID- 9537430
TI  - Defining the outcome of immunosuppression withdrawal after liver transplantation.
AB  - Successful immunosuppression withdrawal should benefit the natural history of
      organ transplantation patients. To identify the clinical hazards of removing drug
      treatment and possible characteristics that predict a favorable outcome in long
      term liver recipients, immunosuppression was withdrawn completely and the
      clinicopathological outcome documented in 18 liver recipients. Indication for
      transplantation, HLA matching, early rejection history, and presence of
      microchimerism were examined as predictors of outcome. Chimerism was determined
      by polymerase chain reaction-based examination for donor-specific HLA-DRB1
      alleles and Y-gene-specific nucleotide sequences. At 3 years, 5 patients (28%)
      remained completely off immunosuppression; 12 patients (67%) experienced
      histological graft changes: acute rejection in 4, portal tract
      inflammation/hepatitis in 7, and necrosis in 1. Hepatitis B or C viral infections
      did not account for the nonrejection patterns. Unmasking of systemic disorders
      occurred. Chimerism, demonstrated in 7 patients (39%), with skin the optimal
      tissue, was not associated with tolerance. Parameters associated with successful
      drug withdrawal were transplantation for non-immune-mediated liver disorders,
      fewer donor-recipient HLA A, B, and DR mismatches, and a low incidence of early
      rejection. Immunosuppression withdrawal is a feasible option in a proportion of
      selected liver recipients, but identification of tolerant patients remains
      imprecise.

PMID- 9537431
TI  - Occupancy of dipeptidyl peptidase IV activates an associated tyrosine kinase and
      triggers an apoptotic signal in human hepatocarcinoma cells.
AB  - Dipeptidyl peptidase IV (CD26/DPP-IV) is an ectoenzyme expressed on different
      cell types. Signaling properties and functional consequences of the CD26
      triggering have been elucidated mostly on T cells, where the molecule delivers a
      costimulatory signal that potentiates T-cell activation through the T-cell
      receptor. We conducted studies in the human hepatocarcinoma-derived PLC/PRF/5
      cell line to examine the signal transduction through CD26 and its functional
      properties in the absence of other T-cell-specific membrane molecules. Engagement
      of CD26 in PLC/PRF/5 cells through a specific antibody induces tyrosine
      phosphorylation of several proteins with maximal intensity 15 minutes after the
      stimulation. This effect was under the negative regulatory control of CD45
      tyrosine phosphatase, in that the addition of orthovanadate clearly enhanced the
      phosphorylation events. Using in vitro kinase assays with CD26
      immunoprecipitates, we observed that a protein or proteins with kinase activity
      are coprecipitated with the CD26 molecule. In addition, unlike Jurkat T cells, in
      which CD26 expression exerts a protective effect against apoptosis, in PLC/PRF/5
      cells CD26 occupancy delivers a potent apoptotic signal. This effect was also
      observed in HepG2 cells, thus indicating that it represents a more general
      phenomenon occurring in different liver neoplastic cell lines.

PMID- 9537432
TI  - New member of aldose reductase family proteins overexpressed in human
      hepatocellular carcinoma.
AB  - The multistep process of liver carcinogenesis involves various genetic and
      phenotypic alterations. To identify genes whose expression is increased during
      hepatocarcinogenesis, differential-display polymerase chain reaction (DD-PCR) was
      used to examine differences in the mRNA composition of hepatocellular carcinoma
      (HCC) versus normal liver (nontumor) tissues. This approach identified 67 cDNAs
      that were preferentially expressed in HCC tissue. When these cDNAs were analyzed
      by reverse-Northern analysis, five were reproducibly expressed at high levels in
      HCC. Interestingly, Northern blot analysis revealed that one of the genes showed
      significantly increased mRNA levels in all five tested tumor samples, while its
      mRNA level in the nontumor samples was minimal. BLAST analysis revealed that this
      gene has high sequence identity with the genes from aldo-keto reductase family of
      proteins including the mouse fibroblast growth factor-induced gene (FR-1) (80%
      identity), mouse vas deferens protein (MVDP) (76%), and human aldose reductase
      (AR) (62%). Expression of this novel AR-related protein in all five tested HCCs
      suggests that this protein may play an important role in liver carcinogenesis.

PMID- 9537433
TI  - Activation of mitogen-activated protein kinases/extracellular signal-regulated
      kinases in human hepatocellular carcinoma.
AB  - Mitogen-activated protein kinase/extracellular signal-regulated protein kinase
      (MAPK/ERK) is a key molecule in intracellular signal transducing pathways that
      transport extracellular stimuli from cell surface to nuclei. MAPK/ERK has been
      revealed to be involved in the physiological proliferation of mammalian cells and
      also to potentiate them to transform. However, its role in the outgrowth of human
      hepatocellular carcinoma (HCC) has yet to be clarified. Therefore, in this study,
      we investigated the activation of MAPK/ERK and its associated gene expression in
      HCC. MAPK/ERK was activated in 15 of 26 cases of HCC we examined (58%), and its
      activity level was significantly higher in HCC than in the adjacent non-cancerous
      lesions. Besides, MAPK/ERK activation in HCC was positively correlated with
      protein expression of transcription factor c-Fos. Furthermore, in 25 of 26 cases
      of HCC which genomic DNA was available, 22 cases without genomic DNA
      amplification exhibited positive correlation, not only between protein expression
      of c-Fos and cyclin D1, but also between MAPK/ERK activation and cyclin D1
      expression. Concerning the relationship between MAPK/ERK activation and the
      clinicohistopathological features of HCC, the tumor (HCC) versus non-tumor (non
      cancerous counterpart) ratio (T/N) of MAPK/ERK activity was positively correlated
      with tumor size, but neither with the stage of HCC nor the degree of
      differentiation of HCC. In conclusion, these findings suggest that MAPK/ERK
      activation in human HCC may play an important role in multistep
      hepatocarcinogenesis, especially in the progression of HCC; at least in part,
      through cyclin D1 up-regulation primarily induced by MAPK/ERK via c-Fos.

PMID- 9537434
TI  - Inhibition by dexamethasone of transforming growth factor beta1-induced apoptosis
      in rat hepatoma cells: a possible association with Bcl-xL induction.
AB  - The authors previously reported that transforming growth factor beta1 (TGF-beta1)
      induces apoptosis in McA-RH7777 (7777) and McA-RH8994 (8994) rat hepatoma cell
      lines. Although these cell lines exhibit different responses to glucocorticoid
      treatment in various cellular functions and gene expression, dexamethasone (DEX)
      inhibited spontaneous and TGF-beta1-induced apoptosis in both. Analysis of
      analogous hormones in TGF-beta1-induced apoptosis in 8994 cells suggested the
      inhibitory effect to be glucocorticoid-specific. By cell-cycle analysis and DNA
      fragmentation assay using sodium butyrate, a G1-arrest-inducing reagent,
      regulation of apoptosis by TGF-beta1 and DEX was shown independent of the cell
      cycle. For elucidation of the mechanisms of anti-apoptotic action of DEX, the
      effects of various chemical probes on this apoptosis model were examined, and
      various reagents known to exhibit anti-apoptotic activity in other experimental
      systems were found to be ineffective. The effect of TGF-beta1 and DEX on cellular
      amounts of several apoptosis-related proteins, members of the Bcl-2 family, Bcl
      2, Bcl-xL, Bcl-xS, Bad, and Bax was also examined. DEX drastically increased Bcl
      xL in both cell lines irrespective of the presence of TGF-beta1. Bcl-2 and Bcl-xS
      proteins were not detected, and Bax and Bad content did not change by treatment
      with TGF-beta1 or DEX. Progesterone (Prog), a partial antagonist for
      glucocorticoid receptor, inhibited the effects of DEX on apoptosis and Bcl-xL
      expression in 8994 cells. Thus, Bcl-xL induction by DEX would appear closely
      associated with its inhibitory effect on spontaneous and TGF-beta1-induced
      apoptosis in the hepatoma cell lines.

PMID- 9537435
TI  - The mouse equivalent of the human p53ser249 mutation p53ser246 enhances aflatoxin
      hepatocarcinogenesis in hepatitis B surface antigen transgenic and p53
      heterozygous null mice.
AB  - The relative contribution to development of hepatocellular carcinoma of the mouse
      equivalent to the human p53ser249 mutation, found in human hepatocellular
      carcinoma associated with aflatoxin (AFB1) exposure, is compared with other major
      risk factors in a transgenic mouse model. Transgenic p53ser246 mice, expressing
      the mutant protein gene under the control of a truncated albumin promoter, were
      bred to mice lacking p53 (p53-/-) and to transgenic mice expressing hepatitis B
      surface antigen (HBsAg). AFB1 hepatocarcinogenesis was then determined in
      offspring with single or multiple risk factors by determination of the numbers of
      high-grade hepatic tumors at 13 months of age. In AFB1-treated male mice,
      expression of the p53ser246 mutation increases the incidence of high-grade tumors
      from 0% to 14% in HBsAg-negative, p53+/+ (wild-type homozygous) control mice;
      from 14% to 71% in HBsAg-negative, p53+/- (wild-type heterozygous) mice; and from
      62% to 100% in HBsAg-positive, p53+/+ mice. Thus, whereas HBsAg expression and
      AFB1 together are strongly cocarcinogenic, the presence of the p53ser246 mutant
      not only significantly enhances this cocarcinogenic effect, it also increases
      tumorigenesis in AFB1-treated p53 heterozygous and homozygous mice not expressing
      HBsAg. The possibility that the p53ser246 mutant protein may act as a promoting
      agent for AFB1 hepatocarcinogenesis is discussed.

PMID- 9537436
TI  - Expression of E-cadherin, alpha-catenin, beta-catenin, and CD44 (standard and
      variant isoforms) in human cholangiocarcinoma: an immunohistochemical study.
AB  - Immunolocalization of E-cadherin (E-cad), alpha-catenin, beta-catenin, and CD44
      has rarely been investigated in human cholangiocarcinoma (CC). We, therefore,
      immunohistochemically examined the expression of E-cad, alpha-catenin, beta
      catenin, CD44 standard (CD44s), and CD44 variants (CD44v) including CD44v5,
      CD44v6, CD44v7-8, and CD44v10 in normal adult livers and in 47 cases of CC; and
      the results were then correlated with tumor grade, vascular invasion, metastasis,
      p53 expression, proliferative fraction (Ki-67 labeling), and c-erbB2 expression.
      In normal livers, E-cad, alpha-catenin and beta-catenin, but not CD44s, CD44v5,
      CD44v6, CD44v7-8, and CD44v10, were expressed at the cell membrane of normal
      intrahepatic bile ducts. In CC, membranous expression of E-cad, alpha-catenin,
      and beta-catenin was the same or reduced when compared with non-cancerous bile
      ducts in the majority of CC. We found that the down-regulation of E-cad, alpha
      catenin, and beta-catenin expression significantly correlated with tumor high
      grade, but not with vascular invasion, metastasis, p53 expression, Ki-67
      labeling, or c-erbB2 expression, except for beta-catenin, the down-regulation of
      which was associated with c-erbB2 down-regulation. CD44s, CD44v5, CD44v6, CD44v7
      8 and CD44v10 were frequently expressed at the membrane of CC cells. There were,
      however, no significant correlations between these aberrant CD44 expression and
      tumor grade, metastasis, vascular invasion, p53 expression, Ki-67 labeling, or c
      erbB2 expression, with a few exceptions of CD44s and CD44v5. We found that CD44s
      aberrant expression significantly correlated with absence of metastasis and
      vascular invasion, and that CD44v5 aberrant expression significantly correlated
      with p53 under-expression. These results suggest that membranous expression of E
      cad, alpha-catenin, and beta-catenin is reduced in a majority of CC and this down
      regulation correlates with CC high grade, and that beta-catenin down-regulation
      is associated with c-erbB2 down-regulation. The data also suggested that CD44s,
      CD44v5, CD44v6, CD44v7-8, and CD44v10 may be neoexpressed during carcinogenesis
      of CC but this neoexpression does not correlate with tumor progression in CC,
      with the exception of CD44s and CD44v5.

PMID- 9537437
TI  - Variant liver estrogen receptor transcripts already occur at an early stage of
      chronic liver disease.
AB  - Variant estrogen receptors may be found in hepatocellular carcinoma and may
      influence its natural history. Because it is not known whether their occurrence
      is an early or a late event during the course of chronic liver disease or whether
      they cluster in some subgroups of patients, we investigated a series of patients
      in different stages of chronic liver disease. One hundred eleven consecutive
      patients were studied for variant estrogen receptor transcripts by reverse
      transcription polymerase chain reaction of RNA extracted from liver biopsy
      specimens. In chronic active hepatitis, variant estrogen receptor transcripts
      were coexpressed with wild-type significantly more often in men than in women (P
      = .029) and in hepatitis B surface antigen (HBsAg)-positive subjects than in
      subjects positive for antibody to hepatitis C virus (P = .0006). In
      hepatocellular carcinoma, again in men (P = .004) and in HBsAg-positive patients
      (P = .0015), the variant estrogen receptor transcript was overexpressed or
      remained the only one expressed. Patients with liver cell dysplasia presented
      with the same estrogen receptor pattern than patients with hepatocellular
      carcinoma. This further reinforces the significance of liver cell dysplasia as a
      preneoplastic condition. The significantly higher occurrence of variant estrogen
      receptor in men (especially in HBsAg-positive men) already at an early stage of
      disease, like chronic active hepatitis, suggests that the alteration of estrogen
      receptors, favoring uncontrolled proliferation and development of hyperplasia,
      might constitute a prominent mechanism facilitating neoplastic transformation
      especially in men.

PMID- 9537439
TI  - Cytomegalovirus infection is associated with increased inflammation and severe
      bile duct damage in rat liver allografts.
AB  - It has been suggested that cytomegalovirus (CMV) infection is involved in
      allograft rejection. In liver transplantation, it has been suggested that CMV is
      associated with the development of vanishing bile duct syndrome (VBDS), and
      persistent CMV has been found in liver grafts that develop chronic rejection. In
      this experimental study, the effect of rat CMV (RCMV) infection on intragraft
      changes was investigated in a rat model of acute liver allograft rejection. Liver
      transplantations were performed in a rat strain combination of PVG (RT1c) --> BN
      (RT1n). No immunosuppression was given. One group of animals was infected with
      RCMV Maastricht Strain (10(5) plaque-forming units, intraperitoneally), and
      another group was left uninfected. The grafts were examined histologically after
      the rats were killed on postoperative days 7 through 9 at the early phase and
      days 20 through 30 at the late phase of rejection. Immunohistochemical studies
      were performed to demonstrate the immunological activation markers major
      histocompatibility complex class II and interleukin 2 receptors, intercellular
      adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1), and
      their ligands. RCMV infection was demonstrated from the grafts by culture and
      direct antigen detection. In liver allografts undergoing acute rejection, CMV
      significantly increased portal inflammation and caused more severe bile duct
      damage than in the uninfected grafts. CMV was also linked to the induction of
      VCAM-1 in the endothelial cells. The ongoing infection was found to vary over
      time in the different structures of the liver grafts, including the vascular
      endothelium and bile ducts. Our results support an association between CMV
      infection and the immunological mechanisms of rejection, as well as the role of
      CMV in the development of bile duct damage in liver allografts.

PMID- 9537438
TI  - Analysis of CDKN2A, CDKN2B, CDKN2C, and cyclin Ds gene status in hepatoblastoma.
AB  - The status and the expression of cyclin-dependent kinase inhibitor A (CDKN2A)
      family genes, named CDKN2A, CDKN2B, and CDKN2C and of cyclin Ds (D1, D2, and D3)
      genes were investigated in 14 cases of human hepatoblastomas. These genes were
      selected because: 1) CDKN2A and CDKN2B are very frequently inactivated in human
      cancers; 2) cyclin Ds are overexpressed in several tumors and 3) CDKN2A is
      posttranscriptionally silenced in hepatocellular carcinomas. Structural analysis
      of the CDKN2A, CDKN2B, and CDKN2C genes in hepatoblastoma cases showed the
      absence of deletions and/or point mutations. Moreover, a detailed investigation
      of loss of heterozygosity at 9p21 and 1p32 (the chromosomal regions where CDKN2A
      genes are located) rules out the possible loss of one allele. Messenger RNA
      (mRNA) analysis showed that CDKN2C is expressed in all hepatoblastoma samples
      studied, while both CDKN2A and CDKN2B genes are not transcribed in the cancer
      specimens as well as in the matched normal liver tissues. Interestingly, an
      alternative mRNA expressed by the CDKN2A gene (beta-transcript) is detectable in
      100% of the samples investigated. The analysis of cyclin D genes expression
      revealed that cyclin D1 is highly transcribed in normal hepatic tissue while
      cyclin D2 or D3 genes were extensively expressed in the matched transformed
      samples. Investigation at protein level confirmed the data obtained on RNA
      analysis. Indeed, p16INK4A and p15INK4B (products of expression of CDKN2A and
      CDKN2B respectively) were not observable while pl8INK4C (which is codified by
      CDKN2C) was clearly detectable in the samples analyzed. Moreover, a noticeable
      decrease of cyclin D1 content and increase of cyclin D3 level were observable in
      tumor tissues versus normal counterparts. Our findings demonstrated the
      following: 1) CDKN2A, CDKN2B, and CDKN2C genes are structurally unmodified in
      human hepatoblastoma, and 2) CDKN2A (alpha-transcript) and CDKN2B are
      transcriptionally silenced in normal liver whereas CDKN2A (beta-transcript) and
      CDKN2C were clearly expressed. Finally, a clear shift in cyclin D type expression
      was observable during malignant transformation. These results show that CDKN2A
      gene family alterations are not involved in hepatoblastoma development, whereas
      changes in cyclin D types might play a role in this type of tumor. Furthermore, a
      highly regulated expression of CDKN2A seems to occur in normal hepatic tissue.

PMID- 9537440
TI  - (Latent) transforming growth factor beta in liver parenchymal cells, its injury
      dependent release, and paracrine effects on rat hepatic stellate cells.
AB  - Cultured parenchymal liver cells (PC) were recently recognized to contain
      (latent) transforming growth factor beta (TGF-beta) while the expression of TGF
      beta mRNA remains controversial. This study was designed to analyze PC in
      different microenvironments (liver in situ, highly purified, isolated, and
      cultured PC) regarding the qualitative and quantitative content of mature and
      latent TGF-beta protein (immunostainings, enzyme-linked immunosorbent assay
      [ELISA], and enzyme-labeled fluorescence [ELF] technique). The results were
      compared with its gene expression (reverse-transcription polymerase chain
      reaction [RT-PCR]). In all microenvironments, PC contained latent TGF-beta, which
      was partially activated after cell isolation and culture. The amount of total TGF
      beta (mature plus latent) of latency-associated peptide (LAP) and of latent TGF
      beta binding protein (LTBP) were shown to decrease during culture. In contrast,
      TGF-beta2 and TGF-beta3 mRNA and LTBP-1 and -3 mRNA expression were first
      detectable after culture. Permeabilization of cell membranes in whole liver and
      of isolated PC with streptolysin O or carbon tetrachloride, respectively,
      released TGF-beta, a part of which was integrated in the large latent complex as
      estimated by analytical gel filtration chromatography. The TGF-beta released by
      damaged PC induces paracrine effects on hepatic stellate cell cultures. It
      stimulates hyaluronan synthesis and antagonizes the effect of mitogenic factor(s)
      of PC on [3H]thymidine incorporation. The results strongly suggest that the main
      part of hepatocellular TGF-beta is not generated by de novo synthesis but from
      uptake into the liver in vivo. The immunodetection of preexisting mature TGF-beta
      after isolation of the cells is probably caused by intracellular activation of
      latent TGF-beta. The injury-dependent discharge of TGF-beta from PC might be an
      important mechanism for initiation and perpetuation of various forms of chronic
      human liver diseases.

PMID- 9537441
TI  - Hypothyroidism minimizes liver damage and improves survival in rats with
      thioacetamide induced fulminant hepatic failure.
AB  - Recent data from animal studies suggest that induced hypothyroidism prevents the
      hyperdynamic circulation in portal vein ligated rats, liver cirrhosis in rats
      chronically treated with thioacetamide (TAA), and immune-mediated acute liver
      injury induced in mice by concanavalin A. Therefore, the aim of this present
      study is to determine whether hypothyroidism would likewise prevent fulminant
      hepatic failure (FHF) in rats. FHF was induced by 3 consecutive ip injections of
      TAA (400 mg/kg) at 24-hour intervals. Hypothyroidism was induced in rats by
      either methimazole (MMI) or propylthiouracil (PTU) and surgical thyroidectomy and
      was confirmed by elevated serum thyroid stimulating hormone levels. Serum levels
      of liver enzymes, blood ammonia, and prothrombin time were significantly lower in
      all 3 groups of hypothyroid rats. The stage of hepatic encephalopathy (HE) and
      the survival rates were significantly improved in the hypothyroid rats (P < .01);
      the histologic examination of their livers showed less necrosis and inflammation
      (P < .01). In the hypothyroid rats, the serum levels of malondialdehyde 48 hours
      after thioacetamide (TAA) administration were lower than in control rats (P <
      .01). Exogenous supplementation of hypothyroid rats with L-thyroxine started 48
      hours before TAA administration abrogated the protective effects of
      hypothyroidism. The serum levels of tumor necrosis factor alfa (TNF-alpha),
      interleukin (IL) 2 and IL-6 after 24 hours were slightly lower in the hypothyroid
      rats, but the administration of soluble receptor of TNF (10-1,000 microg/rat) did
      not prevent the induction of fulminant liver failure by TAA. Oxygen extraction,
      studied in isolated perfused liver preparation, was significantly lower in livers
      of hypothyroid rats (P < .01). These results suggest that induced hypothyroidism
      decreases the development of liver injury in a rat model of FHF. The mechanism
      may involve diminished oxidative cell injury caused by decreased oxygen
      utilization and hypometabolism associated with hypothyroidism.

PMID- 9537442
TI  - Acetaminophen hepatotoxicity in tumor necrosis factor/lymphotoxin-alpha gene
      knockout mice.
AB  - Recent evidence suggests that macrophages and/or other nonparenchymal cells may
      release important mediators contributing to the hepatic necrosis induced by high
      doses of acetaminophen (APAP). The nature and causative role of these mediators
      has remained elusive, however. To investigate the role of the proinflammatory
      cytokine, tumor necrosis factor (TNF) in the initiation and early propagation of
      APAP-induced liver injury, we have used mice deficient in both TNF and the
      closely related lymphotoxin-alpha (LT-alpha). Male TNF/LT-alpha knockout mice and
      C57BL/6 wild-type mice were treated with a hepatotoxic dose of APAP (400 mg/kg,
      intraperitoneally), and the development of liver injury was monitored over 8
      hours. Both genotypes exhibited similar basal activities of hepatic cytochrome
      P450 2E1 and 1A2. After APAP administration, both the rate of glutathione
      consumption and the extent of subsequent selective protein binding did not differ
      significantly in the knockout and wild-type mice. The TNF/LT-alpha-deficient mice
      developed severe centrilobular necrosis and exhibited highly increased levels of
      serum alanine aminotransferase and aspartate aminotransferase, the extent of
      which was not significantly different from that in wild-type mice. In C57BL/6
      mice exposed to APAP, no increases in hepatic transcripts of TNF or LT-alpha were
      found by reverse transcription-polymerase chain reaction, nor was immunoreactive
      serum TNF detected by enzyme-linked immunosorbent assay over 8 hours
      posttreatment. These data indicate that, in the absence of the genes encoding for
      TNF and LT-alpha, APAP bioactivation was not altered and mice still developed
      severe hepatic necrosis. Thus, TNF is unlikely to be a key mediator in the early
      pathogenesis of APAP-induced hepatotoxicity.

PMID- 9537443
TI  - Hepatic oval cell activation in response to injury following chemically induced
      periportal or pericentral damage in rats.
AB  - Administration of 2-acetylaminofluorene (2-AAF) given before partial hepatectomy
      (PHx) results in suppression of hepatocyte proliferation and stimulation of oval
      cell proliferation. Our objective in this study was to examine the oval cell
      response and associated alpha-fetoprotein (AFP) gene expression by combining 2
      AAF with selective damage of centrilobular regions (carbon tetrachloride [CCl4])
      or periportal regions (allyl alcohol [AA]). Centrilobular damage results in a
      more enhanced oval cell response and AFP gene expression than periportal damage.
      Conversely, more intense proliferation of intraportal bile duct epithelia was
      seen with 2-AAF/AA than with 2-AAF/CCl4. The oval cell response and AFP gene
      expression was ranked as 2-AAF/ CCl4 > or = 2-AAF/PHx > 2-AAF/AA. AFP mRNA
      expression was also examined in an acute AA and CCl4 injury. We found very little
      AFP gene expression compared with the 2-AAF/hepatic injury models. To see a true
      oval cell response, the hepatocytes must be inhibited from proliferating. In
      addition, the results presented with the 2-AA/AA model suggest that the
      periportal matrix may be as important as the cells that populate the area.

PMID- 9537444
TI  - Mitochondrial dysfunction and cytoskeletal disruption during chemical hypoxia to
      cultured rat hepatic sinusoidal endothelial cells: the pH paradox and
      cytoprotection by glucose, acidotic pH, and glycine.
AB  - We investigated mechanisms underlying death of cultured rat liver sinusoidal
      endothelial cells exposed to chemical hypoxia with KCN (2.5 mmol/L) to simulate
      the adenosine triphosphate (ATP) depletion and reductive stress of anoxia. During
      chemical hypoxia, acidotic pH prevented cell death. Glucose (0.3-10 mmol/L) also
      prevented cell killing. Cytoprotection by glucose but not acidosis was associated
      with prevention of ATP depletion. After 4 hours of chemical hypoxia at pH 6.2
      (simulated ischemia), rapid cell death occurred when pH was restored to pH 7.4
      with or without washout of KCN (simulated reperfusion). This pH-dependent
      reperfusion injury (pH paradox) was prevented after KCN washout at pH 6.2.
      Glycine (0.3-3 mmol/L) also prevented the pH paradox, but glucose did not. The
      initial protection by acidotic pH and glycine during simulated reperfusion was
      lost when pH was later restored to 7.4 or glycine was subsequently removed.
      Mitochondria depolarized during chemical hypoxia. After washout of cyanide,
      mitochondrial membrane potential (delta psi) did not recover in cells that
      subsequently lost viability. Conversely, those cells that repolarized after
      cyanide washout did not subsequently lose viability. The actin cytoskeleton and
      focal adhesions became severely disrupted during chemical hypoxia at both pH 6.2
      and 7.4 and did not recover after cyanide washout under any condition. Glucose
      during chemical hypoxia prevented cytoskeletal disruption. In conclusion,
      endothelial cell damage during simulated ischemia/reperfusion involves
      mitochondrial dysfunction, ATP depletion, and ATP-dependent cytoskeletal
      disruption. Glycine and acidotic pH prevented cell killing after reperfusion but
      did not reverse mitochondrial injury or the profound disruption to the
      cytoskeleton.

PMID- 9537445
TI  - Use and outcome of liver transplantation in acetaminophen-induced acute liver
      failure.
AB  - Once defined clinical criteria are fulfilled in acetaminophen-induced
      hepatotoxicity, prognosis without orthotopic liver transplantation (OLT) may be
      very poor. In the present study, we examined the application and outcome of OLT
      in 548 patients admitted to a single center between 1990 and 1996. Four hundred
      twenty-four (77%) of the patients studied did not fulfill transplantation
      criteria, and 396 of these (93%) survived. The majority of the 28 nonsurvivors
      (7%) in this group fulfilled two of three combined criteria, and the finding of a
      high APACHE III score could be used as an indicator for the need for OLT. Of the
      56 patients (45%) not listed, in only a small proportion was this caused by
      psychiatric reasons, and in the majority, it was a consequence of the rapid
      development of multiple organ failure and cerebral edema. This also applied to 24
      (35%) of the 68 listed patients in whom the rapidity of clinical deterioration,
      reflected in increasing APACHE III scores, was such that even with the prompt
      availability of donor organs, OLT was not possible. In the final event, only 44
      (35%) of those who fulfilled criteria underwent OLT, of whom 33 (75%) survived to
      leave the hospital. Survival was greatest in those receiving unreduced grafts,
      and markers of early graft function differed significantly between survivors and
      nonsurvivors. Liver transplantation is an effective treatment in a relatively
      small number of patients with acetaminophen-induced hepatotoxicity, and for a
      substantial proportion, transplantation was never an option because of the
      rapidity of clinical deterioration. APACHE III scoring may be of value in
      decision making and in better defining patients in clinical trials.

PMID- 9537446
TI  - Contribution of the murine mdr1a P-glycoprotein to hepatobiliary and intestinal
      elimination of cationic drugs as measured in mice with an mdr1a gene disruption.
AB  - In the mouse, both the mdr1a and the mdr1b gene encode drug-transporting P
      glycoproteins. The mdr1a P-glycoprotein is expressed in epithelial cells of,
      among others, the liver and the intestine. Furthermore, the mdr1b gene product is
      found in the liver but is not detectable in the intestine. To establish the
      potential involvement of P-glycoprotein in the elimination of cationic
      amphiphilic drugs from the body, we investigated biliary, intestinal, and urinary
      excretion in mice with a homozygous disruption of the mdr1a gene (mdr1a(-/-)
      mice). These mice are fully viable under laboratory conditions and have normal
      bile flow. Cumulative biliary excretion (expressed as percent of the
      intravenously administered dose excreted over a 1-hour period) of several
      cationic compounds was decreased as follows in mdr1a(-/-) mice compared with the
      wild-type animals: tri-n-butylmethylammonium (TBuMA), 0.7% versus 2.1%;
      azidoprocainamide methoiodide (APM), 3.8% versus 7.6%; and vecuronium, 22.7%
      versus 41.3%. The luminal secretion of both TBuMA and APM in the small intestine
      was profoundly decreased, respectively 4.6-fold (1.8% vs. 8.2% in the wild-type)
      and 7.9-fold (1.6% vs. 10.3% in the wild-type) in mdr1a(-/-) mice. Thus mdr1a P
      glycoprotein contributes substantially to the removal of a wide variety of
      cationic agents from the body through intestinal and hepatobiliary secretion, but
      it evidently acts in concert with other transport system(s). These processes
      probably provide a protective mechanism limiting the overall rate of absorption
      as well as the bioavailability of potentially toxic organic amines.

PMID- 9537447
TI  - Ethanol up-regulates fatty acid uptake and plasma membrane expression and export
      of mitochondrial aspartate aminotransferase in HepG2 cells.
AB  - To explain the increased plasma mitochondrial aspartate aminotransferase (mAspAT)
      observed in alcoholics, we cultured HepG2 hepatoma cells in ethanol. Acute (24
      hour) exposure to 0, 20, 40, or 80 mmol/L ethanol produced a dose-dependent (r =
      .98) increase in mAspAT messenger RNA (mRNA) of < or = thirteen-fold, with no
      significant change in the cellular content of mAspAT or of several other enzymes.
      The recovery of mAspAT in the medium over 24 hours of ethanol exposure correlated
      with both ethanol concentration and with mAspAT mRNA (r = .90), reaching 808% of
      cellular enzyme content/24 hours at 80 mmol/L. Recovery of all other enzymes
      studied was < or = 20% of cellular content and unaffected by ethanol. Plasma
      membrane mAspAT content also correlated with mAspAT mRNA (r = .96) and
      mitochondrial levels were unchanged. No mitochondrial morphologic abnormalities
      were observed at any ethanol concentration studied. In cells cultured chronically
      at 0 to 80 mmol/L ethanol, fatty acid uptake Vmax increased in parallel with
      plasma membrane expression of mAspAT (r = .98). Cellular triglyceride content was
      highly correlated with Vmax. Thus, the data suggest that: 1) the increased plasma
      mAspAT observed in alcoholics may reflect pharmacologic upregulation of mAspAT
      mRNA and of mAspAT synthesis by ethanol; and 2) increased mAspAT-mediated fatty
      acid uptake may contribute to alcoholic fatty liver.

PMID- 9537448
TI  - The surface of rat hepatocytes can transfer iron from stable chelates to external
      acceptors.
AB  - The chelator diethylenetriaminepentaacetate (DTPA) forms a stable complex with
      iron that does not donate iron to transferrin under physiological conditions,
      i.e., pH above 7 and isotonic milieu. It does, however, deliver iron to
      hepatocytes. This uptake is initiated by a mobilization of the metal from the
      complex by the cell surface. When an external chelator is added simultaneously,
      it can bind the iron and inhibit its accumulation by the cells. This is shown
      here with the impermeant siderophore conjugate hydroxyethyl-starch coupled
      desferrioxamine, as well as with apotransferrin. We also demonstrate exchange of
      iron between DTPA and holo-transferrin, or at least movement from the chelator to
      the protein, which may have lost its iron to the cell in advance, providing new
      binding sites for mobilized iron. The efficient hepatocyte iron donor lactoferrin
      greatly stimulates iron uptake from DTPA, apparently by binding iron and
      transferring it into the cells by endocytosis. Ferritin is unable to do this;
      therefore, the mobilization of iron is not caused by a reducing activity at the
      cell surface, because iron is readily transferred from DTPA to ferritin by the
      reductant ascorbic acid. The transfer process is dependent on the temperature,
      the time, and the amount of cells present, and is partly inhibited by sulfhydryl
      reagents. We conclude that this activity represents a hitherto unidentified first
      step in the movement of iron through the cell membrane and may be relevant for
      transferrin-bound, as well as for non-transferrin-bound, iron uptake by
      hepatocytes.

PMID- 9537449
TI  - p21Ras downstream effectors are increased in activity or expression in mouse
      liver tumors but do not differ between ras-mutated and ras-wild-type lesions.
AB  - Mouse liver tumors frequently harbor activating ras gene mutations. Downstream
      effector molecules of p21Ras include Raf-1 kinase which mediates external signals
      via kinase signaling pathways to nuclear transcription factors including c-Fos
      and c-Jun. Mouse liver tumors with differing ras-mutational status were analyzed
      for alterations in Ras/Raf-1 signal transduction. Tumors were characterized with
      respect to the presence of base substitutions in the 3 known hot-spot positions
      at codons 12, 13, and 61 of Ha-ras, Ki-ras, and N-ras. Ha-ras codon 61 or Ki-ras
      codon 13 mutations, but no N-ras mutations, were detected in 23 out of 33 tumors
      analyzed, while no ras-mutations were found in 10 of the tumors. There was no
      significant difference in the expression of p21RaS proteins between ras-mutated
      tumors and tumors without detectable ras mutations. To allow for determination of
      Raf-1 kinase activity in tumors, a sensitive and specific assay was developed for
      measurements with tissue homogenates. Raf-1 kinase activity was increased about
      four-fold in liver tumors as compared with normal liver tissue. No significant
      differences in kinase activity, however, were evident between ras-mutated and ras
      wild-type tumors. The same was true with respect to the levels of c-fos and c-jun
      mRNAs. Moreover, there were no significant differences in cell division (5-bromo
      2'-deoxyuridine-labeling indices) of hepatocytes from ras-mutated and ras-wild
      type tumors. The similar degree of constitutive activation of the Ras/Raf-1
      signaling pathway in liver tumors, with and without detectable ras mutations,
      suggests that other molecules within the signaling pathway may substitute for ras
      mutations during oncogenic conversion of ras-wild-type hepatocytes.

PMID- 9537450
TI  - Functional involvement of proteins, interacting with sphingolipids, in
      sphingolipid transport to the canalicular membrane in the human hepatocytic cell
      line, HepG2?
AB  - A photoreactive sphingolipid precursor was used to investigate the potential
      involvement of protein-lipid interactions that may convey specificity to
      sphingolipid transport in the human hepatoma cell line, HepG2. A 125I-labeled,
      photoreactive ceramide, 125I-N3-Cer, was incubated with the cells and became
      incorporated into two sphingolipid products. The major product was photoreactive
      sphingomyelin (125I-N3-SM) (25% of total radioactivity), while only minor amounts
      of photoreactive glucosylceramide (125I-N3-GlcCer) were formed (< 2%). After
      photoactivation, a restricted number of proteins was labeled. Given the absolute
      amounts of the newly synthesized, photoreactive lipids and their precursor
      present in the cells, labeling of the proteins can be assumed to be derived from
      interaction with either ceramide (Cer) or sphingomyelin (SM), or both. To
      discriminate between these possibilities, photoactivation and protein analysis
      was performed in cells treated with D-threo-1-phenyl-2-decanoyl amino-3
      morpholino-1-propanol (PDMP), an inhibitor of sphingolipid biosynthesis. In
      treated cells, the radioactive SM pool was reduced by approximately 80%.
      Concomitantly, labeling of a 60-kd protein, seen in control cells, decreased.
      Furthermore, the 60-kd protein is membrane-associated and insoluble in detergent
      at low temperature. Moreover, when cells containing photoreactive sphingolipids
      after a preincubation with the photoreactive Cer were photoactivated and
      subsequently incubated with fluorescent sphingolipid analogs, transport of the
      latter to the bile canalicular membrane, as observed in control cells, was
      inhibited. Taken together, the data suggest that distinct proteins, among them a
      60-kd protein, may play a specific and functional role in sphingolipid transport
      to the bile canalicular membrane.

PMID- 9537451
TI  - Zonal and regional differences identified from precision mapping of vitamin A
      storing lipid droplets of the hepatic stellate cells in pig liver: a novel
      concept of addressing the intralobular area of heterogeneity.
AB  - Knowledge of hepatic heterogeneity has been strikingly increased, while an
      accurate means for addressing intralobular positions is still lacking. We
      examined pig liver preparations of the gold impregnation method for vitamin A
      storing lipid droplets in hepatic stellate cells. Droplet morphometry was
      performed under oil immersion, and the calculated volumes plotted on computerized
      maps. The heterogeneous results were assessed with five concentric zones and five
      radial regions; the latter were determined based on midseptum visualized by
      portal injection. Zonation and regionation thus subdivided lobules into 5-zone/5
      region (5Z/5R) compartmentalization. Distribution of values exhibited a distinct
      zonal gradient, heightened at peripheral zones 1 and 2, decreased over
      intermediate zone 3 toward centrilobular zones 4 and 5; peak was always found at
      zone 2. Within a single zone, variations were obvious, forming a regional
      gradient. Values were significantly higher at periportal than midseptal regions.
      Digitized mapping showed that low values filled up centrilobular zones, whereas
      high values concentrated in periportal regions. Along the periphery, inlet
      venules were quantified, revealing an occurrence rate of 60% at periportal, and
      5% at midseptal regions, closely compatible with the regional gradient of vitamin
      A-storing capacity. The interweaving between zonal and regional gradients results
      in a vitamin A-low territory, a compound area composed of centrilobular zones
      plus extensions into midseptal regions. Because the results could account for
      physiological and pathological events, we regard the 5Z/5R compartmentalization a
      model worth routine adoption for a precise description of any morphofunctionally
      demonstrable heterogeneity of the liver lobules.

PMID- 9537452
TI  - Expression of hepatitis B virus X protein in HBV-infected human livers and
      hepatocellular carcinomas.
AB  - Transactivation of cellular genes and functional inactivation of p53 by the
      hepatitis B virus (HBV) X gene-encoded protein (HBx) are proposed as alternative
      mechanisms for induction of hepatocellular carcinomas (HCCs) in chronic HBV
      infection. Using an immunohistochemical approach, we studied the expression of
      HBx in 39 explanted livers with HBV-associated disease. Because the data reported
      previously have been inconsistent, possibly due to the application of different
      antibodies, we compared results with 5 polyclonal and 6 monoclonal anti-HBx
      antibodies from five laboratories. Ten of the 11 antibodies reacted with
      recombinant HBx by Western blotting, but only 1 polyclonal and 2 monoclonal
      antibodies reacted specifically with HBx in tissue, and were thus suitable for
      immunohistochemistry. Three other polyclonal antibodies reacted with tissue
      components in addition to HBx. One polyclonal and 4 monoclonal antibodies did not
      recognize the HBx in the tissue. HBx was demonstrated in 16 of 30 (53.3%)
      cirrhotic livers and 10 of 18 (58.8%) HCCs by all specific antibodies. The
      expression of HBx, among three HBV antigens examined, was found to be
      preferentially maintained in HCC and the surrounding liver parenchyma, including
      focal or nodular preneoplastic lesions. However, the immunoreactivity was always
      limited to the cytoplasm of a small number of parenchymal and neoplastic cells.
      The role of X gene expression in HBV-associated human hepatocarcinogenesis
      remains to be established.

PMID- 9537453
TI  - Lymphoblastoid interferon alfa-n1 improves the long-term response to a 6-month
      course of treatment in chronic hepatitis C compared with recombinant interferon
      alfa-2b: results of an international randomized controlled trial. Clinical
      Advisory Group for the Hepatitis C Comparative Study.
AB  - The aim of this study was to compare the short-term and long-term efficacy and
      safety of lymphoblastoid interferon with a recombinant interferon alfa (IFN
      alpha) in a 24-week treatment course for chronic hepatitis C. One thousand
      seventy-one patients with chronic hepatitis C were randomized to receive
      lymphoblastoid IFN-alpha n1 or recombinant IFN-alpha2b at the same dosing
      regimen, 3 million units administered subcutaneously three times a week for 24
      weeks. Hepatitis C viral (HCV) genotype (by line probe assay) was determined at
      baseline, and serum HCV RNA level (by quantitative reverse-transcriptase
      polymerase chain reaction) was measured at baseline and weeks 24, 48, and 72.
      Primary end points were normalization of serum alanine aminotransferase (ALT)
      levels at end of therapy (week 24) and sustained ALT normalization at weeks 48
      and 72. Secondary end points were nondetectability of serum HCV RNA at 24, 48,
      and 72 weeks, and histological improvement at weeks 24 and 72. The two treatment
      groups were similar with respect to demographic, clinical, and histological
      variables (10% had cirrhosis at entry), baseline serum HCV RNA levels, and
      distribution of HCV genotypes. Intent-to-treat analysis showed that ALT response
      at end of treatment was 35.3% for IFN-alpha n1 and 37.9% for IFN-alpha2b (P =
      .38). Histological improvement and nondetectability of HCV RNA were also similar
      between the two treatment groups at the end of treatment, as were the type and
      frequency of reported adverse experiences. Among treatment responders, post
      treatment relapse was significantly less frequent with IFN-alpha n1 than with IFN
      alpha2b. Thus, sustained ALT responses (SR) to IFN-alpha n1 were significantly
      more frequent than SR to IFN-alpha2b (12.0% vs. 7.6% at 48 weeks, P = .02; 10.3%
      vs. 6.7% at 72 weeks, P = .04). SR were associated with viral loss and
      histological improvement, and more patients treated with IFN-alpha n1 were HCV
      RNA negative at week 72 compared with patients treated with IFN-alpha2b (P =
      .03). SR at week 72 were two- to sixfold better with other HCV genotypes relative
      to type 1, but the improved long-term efficacy of IFN-alpha n1 compared with IFN
      alpha2b was evident for all major HCV genotypes. It is concluded that IFN-alpha
      n1 and IFN-alpha2b have similar end-of-treatment response rates and safety
      profiles but the sustained response rate is higher with IFN-alpha n1. SR to IFN
      alpha treatment are associated with clearance of HCV RNA, and histological
      improvement was maximal in patients who exhibited sustained ALT normalization and
      clearance of HCV RNA.

PMID- 9537454
TI  - Combination therapy with thymosin alpha1 and interferon for the treatment of
      chronic hepatitis C infection: a randomized, placebo-controlled double-blind
      trial.
AB  - Hepatitis C is a major cause of liver disease leading to cirrhosis. Although
      interferon (IFN) is the only approved therapy, treatment is characterized by low
      response rates and dose-limiting side effects. We evaluated the addition of
      thymosin alpha1 (TA1), an immunomodulatory peptide, to the standard treatment
      regimen for hepatitis C to determine if combination therapy shows biological
      activity using outcome measures including normalization of alanine
      aminotransferase levels, histological activity, and viral load during treatment.
      We performed a randomized, double-blind, placebo-controlled trial to compare the
      biological activity of a combination TA1 and IFN with that seen for IFN alone in
      patients with chronic hepatitis C infection. One hundred nine patients were
      randomized for intention to treat and received 1.6 mg of TA1 subcutaneously twice
      weekly and 3 MU of IFN three times weekly; 3 MU of IFN three times weekly and
      placebo TA1; or placebo for both agents. All patients had chronic HCV infection
      with confirmation of chronic hepatitis on liver biopsy. Biochemical responders
      were followed up until alanine aminotransferase (ALT) levels became abnormal or
      for 26 weeks, and relapsers were retreated for 26 weeks in the same treatment
      arm. One hundred three patients completed treatment for 26 weeks, and six
      patients dropped out. The groups were similar with regard to sex, gender
      distribution, baseline histological activity index (HAI) score, risk factors, and
      viral titers. End-of-treatment biochemical response was seen in 37.1% of patients
      treated with combination therapy, 16.2% of patients treated with IFN alone, and
      2.7% of untreated controls by intent-to-treat analysis (IFN/TA1 vs. IFN, chi2 =
      4.05, P = .04). HCV RNA clearance was seen in 37.1% of IFN/TA1-treated patients
      and 18.9% of IFN-treated subjects. Mean HCV RNA titers were significantly lower
      than baseline at weeks 8, 16, and 24 after drug initiation among patients treated
      with IFN/TA1 but not in the other treatment arms. Histological improvement, as
      evidenced by a decrease in HAI of more than two points, occurred in the
      combination therapy arm more frequently than in comparison groups. Cumulative
      sustained biochemical responses were 14.2% and 8.1% in the IFN/TA1 and IFN arms,
      respectively, based on an intention-to-treat model. The combination of TA1 and
      standard IFN treatment for chronic hepatitis C showed evidence of biological
      activity at the completion of treatment by biochemical, histological, and
      virological outcome measures. Further research involving longer duration and
      varied dosing is needed.

PMID- 9537455
TI  - Re-treatment of chronic hepatitis C with consensus interferon .
AB  - A multicenter, open-label, phase 3 study was conducted in 337 patients with
      chronic hepatitis C virus (HCV) infection who had either not responded to
      previous interferon therapy or had relapsed after discontinuation of therapy with
      either consensus interferon (9 microg) or interferon alpha-2b (3 million U) three
      times a week for 24 weeks. Patients were randomized to receive a higher dose of
      consensus interferon (15 microg) administered subcutaneously three times a week
      for 24 or 48 weeks and then were observed for an additional 24 weeks. Patients
      who had relapsed after prior interferon therapy were more likely to have a
      sustained alanine aminotransferase response and HCV RNA response (as measured by
      reverse transcription-polymerase chain reaction with a sensitivity of < 100
      copies/mL) than were patients who had not responded to prior interferon therapy.
      For relapsers, the sustained HCV RNA response rate was 58% (48 weeks) and 28% (24
      weeks). The sustained alanine aminotransferase response for relapsers was 52% (48
      weeks) and 39% (24 weeks). The sustained HCV RNA response rate among prior
      nonresponders was 13% (48 weeks) and 5% (24 weeks), and the sustained alanine
      aminotransferase response rate for nonresponders was 17% (48 weeks) and 12% (24
      weeks). The administration of 15 microg of consensus interferon was well
      tolerated and was not associated with an increase in the incidence of side
      effects. These data demonstrate that re-treatment with 15 microg of consensus
      interferon is safe and effective therapy for patients with chronic hepatitis C
      who have either not responded to previous interferon therapy or relapsed after
      discontinuation of interferon therapy.

PMID- 9537456
TI  - Re-treatment with interferon alfa of patients with chronic hepatitis C.
AB  - Treatment of patients with chronic hepatitis C has had limited success because of
      relapses and nonresponse to interferon alfa therapy (currently the only
      established therapeutic agent). A retrospective study was done to determine the
      efficacy of re-treatment with interferon and the predictors of response in
      patients who failed to achieve sustained response after one standard course of
      interferon therapy (3 million units three times a week for 24 weeks). One hundred
      and eleven patients (47 relapsers and 64 nonresponders), mean age 45 years, were
      included in the study. Eighteen relapsers and 13 nonresponders received a higher
      dose (5 MU), and 11 relapsers and 6 nonresponders received a longer duration (48
      weeks) of interferon therapy. The remaining patients received the same regimen as
      the first treatment. Eighty-one percent and 23% of relapsers and nonresponders,
      respectively, had an end-of-treatment response, and 19% and 3% of the
      corresponding patient groups had a sustained response to re-treatment. Two
      patients with breakthrough during their first treatment were the only
      nonresponders with sustained response after re-treatment. Sustained response was
      observed only in patients who received an increased dose or duration of
      interferon therapy. No predictor of sustained response was found. In conclusion,
      sustained response to re-treatment with interferon was only observed with
      augmentation of dose or duration of therapy in some relapsers and patients who
      had breakthrough. Established predictors of response to interferon in naive
      patients, in particular serum hepatitis C virus RNA and genotype, were not
      associated with sustained response to re-treatment.

PMID- 9537457
TI  - Quantification of the initial decline of serum hepatitis C virus RNA and response
      to interferon alfa.
AB  - Although several virus- and host-related predictive factors for the response to
      interferon alfa (IFN-alpha) have been defined in patients with chronic hepatitis
      C, no pretreatment parameter can definitely predict the response to antiviral
      treatment. Assessment of the initial response by quantification of serum
      hepatitis C virus RNA before and 4 weeks after initiation of therapy may be a
      clinically applicable and reliable parameter to predict long-term response.
      Therefore, the aims of the present study were to test the predictive value of a
      decline in HCV RNA of at least 3 log in the first 4 weeks of treatment (deltaHCV
      RNA) in patients treated with 3 x 10(6) units of recombinant IFN-alpha2a (rIFN
      alpha2a) three times per week subcutaneously and to compare deltaHCV RNA with
      other established predictive factors, such as HCV genotype and pretreatment
      viremia. Serum HCV RNA was measured by a validated quantitative reverse
      transcription-polymerase chain reaction (RT-PCR). Geno/subtyping of HCV was
      performed by direct sequencing of the nonstructural (NS) 5B region of PCR
      amplified isolates and subsequent phylogenetic analysis. Stable HCV RNA levels
      (deltaHCV RNA < or = 1 log) within the first 4 weeks of IFN-alpha treatment were
      present in 42 of 70 patients. A decline in HCV RNA levels between 1 to 3 log and
      more than 3 log was observed in 9 (13%) and 19 patients (27%), respectively. In
      21 of 70 patients (30%), HCV RNA was not detectable at the end of 12 months'
      treatment. Three of 26 patients (11%) with a pretreatment viremia of < or = 10(6)
      copies/mL (all HCV subtype 3a) and 6 of 44 patients (14%) with a pretreatment
      viremia of > 10(6) copies/mL (HCV subtypes 1b, 2a, 2c, 3a [two patients], and 4)
      achieved a virological sustained response to interferon-alpha2a treatment. All
      patients with a virological sustained response had an initial deltaHCV RNA of
      more than 3 log. In a stepwise discriminant-function analysis, the initial
      deltaHCV RNA was confirmed as the strongest predictor of virological sustained
      response (P < .0001). In conclusion, the data of the present study suggest that
      IFN-alpha treatment can be terminated after 4 weeks in patients with a decrease
      in HCV RNA levels of less than 3 log, when apparent HCV eradication is considered
      the therapeutic target. The predictive value of deltaHCV RNA clearly exceeds the
      significance of HCV genotype and pretreatment viremia as predictors of successful
      IFN-alpha treatment.

PMID- 9537458
TI  - Budd-Chiari syndrome in patients with hematological disease: a therapeutic
      challenge.

PMID- 9537459
TI  - Modulation of aspartate aminotransferase release and fatty acid uptake by
      ethanol.

PMID- 9537460
TI  - Thrust and parry of hepatocytes regains respect on the liver regeneration front.

PMID- 9537461
TI  - Cytochrome P450 products and renal function in cirrhosis: the HETE is on.

PMID- 9537462
TI  - Significance of repeatedly normal aminotransferase activities in hepatitis C
      virus-infected patients.

PMID- 9537463
TI  - Aprotinin in liver transplantation.

PMID- 9537465
TI  - Histology of the stomach and duodenum in Crohn's disease.
AB  - Crohn's disease (CD) not uncommonly affects the stomach and duodenum, but its
      histologic appearance is not well described beyond the identification of
      granulomas. We retrospectively identified 209 upper gastrointestinal biopsy
      samples from 80 sets of biopsies from 49 patients with CD. Age- and sex-matched
      control biopsies were selected from recent cases of Helicobacter pylori gastritis
      (73 biopsy samples from 34 patients), from patients with a known history of
      nonsteroidal antiinflammatory drug use (18 biopsy samples from 12 patients), and
      from three patients with ulcerative colitis. Architectural and inflammatory
      changes were evaluated and compared. Over three fourths of the patients with CD
      had abnormal biopsy results. Fifty-six percent of patients with CD had acute
      inflammation, but only 10% of the patients were infected with H pylori. Focal
      acute inflammation was a characteristic of H pylori-negative CD (stomach, 31%;
      duodenum, 40%), which was much less common in the non-CD group (stomach, 2%;
      duodenum, 8%). Surface intraepithelial neutrophils of the duodenum were more
      common in H pylori-negative patients with CD (25%) than in those who did not have
      CD (4%), and deep acute inflammation of the duodenum was more likely in H pylori
      negative patients with CD (19% vs. 0%). Granulomas were found in only 9% of the
      CD group. Focal acute inflammation of the gastroduodenum, especially in a
      background of noninflamed mucosa, is strong evidence for CD in the appropriate
      clinical context, but the stomach and duodenum must be properly sampled and
      carefully examined for any evidence of H pylori.

PMID- 9537464
TI  - Chemokine involvement in hepatic ischemia/reperfusion injury in mice: roles for
      macrophage inflammatory protein-2 and KC.
AB  - Hepatic injury induced by ischemia and reperfusion is an important clinical
      problem after liver resection or transplantation. Neutrophils are known to
      mediate the organ injury, but the precise mechanisms leading to hepatic
      neutrophil recruitment are undefined. Two CXC chemokines, macrophage inflammatory
      protein-2 (MIP-2) and KC, are potently chemotactic for neutrophils in vitro and
      have been reported to be involved in neutrophil-dependent inflammatory tissue
      injury. The objective of the present study was to determine the roles of MIP-2
      and KC in the induction of hepatic ischemia/reperfusion injury. C57BL/6 mice were
      subjected to 90 minutes of partial hepatic ischemia followed by reperfusion.
      Hepatic injury was associated with neutrophil sequestration, edema, and elevated
      serum levels of hepatic transaminases. The expression of MIP-2 messenger RNA
      (mRNA) was induced within 3 hours after reperfusion, before any detectable
      increase in neutrophil accumulation, and was also increased to a greater extent
      in the ischemic lobe after 9 hours of reperfusion. These data suggest that MIP-2
      may be involved in the initial recruitment of neutrophils to the ischemic lobe.
      In contrast, KC mRNA expression was not increased after 3 hours of reperfusion
      but after 9 hours increased equivalently in both ischemic and non-ischemic lobes,
      suggesting a more generalized role in neutrophil recruitment. Neutralization of
      MIP-2 or KC resulted in significant decreases in hepatic neutrophil accumulation,
      edema, and hepatocellular injury. These data suggest that the local expression of
      MIP-2 and KC are important mediators involved in neutrophil-dependent hepatic
      injury induced by ischemia and reperfusion in mice.

PMID- 9537466
TI  - Pulmonary adenocarcinomas of the fetal lung type: a clinicopathologic study
      indicating differences in histology, epidemiology, and natural history of low
      grade and high-grade forms.
AB  - Seven cases of high-grade adenocarcinoma of fetal lung type (H-FLAC) are compared
      with nine cases of pulmonary endodermal tumor resembling fetal lung or low-grade
      adenocarcinoma of fetal lung type (L-FLAC). Of the seven patients with of H-FLAC,
      four were men and three were women. All of the patients but one were in their 60s
      or 70s. Five patients were smokers. After resection of the tumor, three patients
      died of metastases, two patients are alive with no evidence of disease, and two
      patients died of a postoperative complication. Histologically, H-FLAC and L-FLAC
      have both complex glandular structures resembling fetal lung and neuroendocrine
      differentiation. Two cases of H-FLAC had stromal proliferation typical of
      biphasic pulmonary blastoma. The H-FLAC was distinguished from L-FLAC by the
      presence of disorganized glands, large vesicular nuclei, prominent nucleoli,
      pronounced anisonucleosis, absence of morules, transition to conventional
      adenocarcinoma, broad areas of necrosis, desmoplastic stroma, overexpression of
      p53 protein, and production of alpha-fetoprotein. High and low grades of FLAC
      explain discrepancies in previously reported clinicopathologic features of FLAC.
      The H-FLAC needs to be distinguished from L-FLAC. Both forms may have stromal
      components, so both have been referred to as blastomas. The H-FLAC represents the
      prototype of so-called pulmonary blastoma predominantly seen in the elderly,
      whereas L-FLAC and its biphasic form predominate in the middle-aged population.

PMID- 9537467
TI  - Inflammatory myofibroblastic tumor of the pancreaticobiliary region: morphologic
      and immunocytochemical study of three cases.
AB  - Inflammatory myofibroblastic tumor (IMT) is a rare tumor of the
      pancreaticobiliary region. The etiology and biologic behavior of IMTs at this
      site are unknown. We present three patients with IMT of the pancreaticobiliary
      region, each with long-term follow-up. In all three cases a second tumor
      developed. Grossly these tumors mimicked a malignant process. Microscopically,
      all were composed of an admixture of spindle cells and chronic inflammatory
      cells, including plasma cells, lymphocytes, eosinophils, and macrophages. The
      spindle cells stained positively for smooth muscle actin and vimentin but were
      negative for S-100, cytokeratin, CD35, and latent membrane protein. Results of in
      situ hybridization with EBER probes were negative in all cases. In addition to
      carcinoma, the differential diagnosis of these tumors includes follicular
      dendritic cell tumor and inflammatory fibrosarcoma. The importance of extensive
      pathologic examination to prevent misdiagnosis and the need for long-term follow
      up are emphasized. This subset of IMT does not appear to be related to Epstein
      Barr virus.

PMID- 9537468
TI  - Colloidal iron staining in renal epithelial neoplasms, including chromophobe
      renal cell carcinoma: emphasis on technique and patterns of staining.
AB  - Positive staining with Hale's colloidal iron stain, or modifications thereof, is
      considered a diagnostic feature for chromophobe renal cell carcinoma and has been
      used as a discriminatory feature to differentiate it from other renal tumors. We
      studied colloidal iron staining in 62 cases encompassing a wide histologic
      spectrum of renal neoplasms (14 chromophobe renal cell carcinomas, 19 renal
      oncocytomas, 11 each of granular variants and conventional clear cell renal cell
      carcinomas, and 7 eosinophilic variants of papillary renal cell carcinoma) to
      investigate the specificity of the stain for chromophobe renal cell carcinoma. In
      cases of chromophobe renal cell carcinoma, sections from two different areas were
      stained to ascertain whether there was any spatial variation in staining.
      Influence of staining techniques on the results also was investigated by staining
      each case of chromophobe renal cell carcinoma using two different methods: the
      traditional Hale's and a modified Mowry's technique, which treats sections with
      3% acetic acid before adding the colloidal iron. Our results show that positive
      staining with colloidal iron stain is not limited to chromophobe renal cell
      carcinoma, however, a diffuse and strong, reticular staining pattern was observed
      only in cases of chromophobe renal cell carcinoma (14 of 14). The staining
      patterns were less consistent in all other renal neoplasms and differed from the
      reaction observed in chromophobe renal cell carcinoma. Most renal oncocytomas (16
      of 19) had focal and weak, fine dustlike positivity, and all clear cell
      carcinomas showed focal, coarse, dropletlike positive staining (22 of 22), in
      addition to a focal, coarse, bubbly pattern in 5 of 11 clear cell subtypes.
      Although all seven cases of the eosinophilic variant of papillary renal cell
      carcinoma showed strong, coarse, dropletlike staining, most of the positivity was
      coincident with the Perl's (prussian blue) reaction, indicating that the staining
      was due to hemosiderin, which is frequently present in this histologic subtype of
      renal cell carcinoma. Staining intensity did not vary considerably among
      different areas of chromophobe renal cell carcinoma, but the modified Mowry's
      method yielded brighter and sharper reticular staining, as compared with the
      Hale's method. Our results show that in the appropriate morphologic context
      diffuse and strong reticular positivity using the modified Mowry's colloidal iron
      stain method is highly characteristic for chromophobe renal cell carcinoma.
      Treatment of sections with 3% acetic acid before adding the colloidal iron gives
      technically superior staining results.

PMID- 9537469
TI  - Nasal chondromesenchymal hamartoma: an upper respiratory tract analogue of the
      chest wall mesenchymal hamartoma.
AB  - Nasal chondromesenchymal hamartoma is the suggested appellation for a tumefactive
      process of the nasal passages and contiguous paranasal sinuses in seven children
      with a detectable mass in the nose. With the exception of one patient who was 7
      years of age at diagnosis, the others were 3 months of age or less upon
      recognition of the mass. Two children were diagnosed in the first 2 weeks of
      life. Imaging studies showed a complex solid and cystic mass or masses filling
      the nasal cavity and extending into the ethmoid sinuses in most cases. Erosion of
      the surrounding bone, including the cribriform plate, resulted in an intracranial
      component in the four cases. Surgical resection was the treatment of choice
      despite its technical difficulties that often necessitated a combined intranasal
      and intracranial approach. Residual disease with continued growth in one case was
      the clinical outcome in two children, and the remaining five patients have not
      experienced any further difficulties. The piecemeal fragments of tissue disclosed
      a collage of histologic features, but the basic morphologic elements were well
      demarcated nodules of cartilage with some variation in the cellular density and
      maturation of the chondrocytes, a myxoid to spindle cell stroma, focal
      osteoclastlike giant cells in the stroma, and erythrocyte-filled spaces
      resembling those of the aneurysmal bone cyst. Two of the tumors were less
      polymorphous or complex in their spectrum of histologic features. These nasal
      masses have similarities to the so-called chest wall hamartoma or mesenchymal
      hamartoma of the chest wall in terms of the clinical presentation in infancy and
      the basic cartilaginous character of both entities. There is a degree of
      presumption in the designation of these nasal and chest wall tumors as hamartomas
      because the pathogenesis has not been established for either entity.

PMID- 9537470
TI  - Apoptotic bodies: a consistent morphologic feature of endocervical adenocarcinoma
      in situ.
AB  - To evaluate the occurrence of apoptotic bodies in endocervical adenocarcinoma in
      situ (AIS) and investigate the relationship of apoptosis to mitotic activity, we
      performed counts of apoptotic bodies and mitotic figures in 43 patients with AIS
      and in a comparable control group with nonneoplastic endocervical glandular
      epithelium. The ages of the patients with AIS ranged from 27 to 74 years (mean =
      40). Mitotic figures were present in all AIS cases, and apoptotic bodies were
      seen in all but two extremely small lesions. In 28 AIS cases in which lesions
      were large enough to count 10 consecutive high-power fields (HPF), counts of
      apoptotic bodies ranged from 1 to 36/10 HPF (mean and median = 16), and counts of
      mitotic figures ranged from 1 to 53 mitotic figures/10 HPF (mean and median =
      18). Counts of apoptotic bodies correlated directly with counts of mitotic
      figures. The ages of the 28 control patients ranged from 32 to 56 years (mean =
      43). Counts of apoptotic bodies in the control cases ranged from 0 to 10 per case
      (mean = 1.1). Apoptotic bodies were present in only 13 (46%) control cases. The
      highest counts in these cases ranged from 1 to 6 apoptotic bodies/10 HPF (mean =
      2.3). Mitotic figures were present in only 4 (14%) control cases. The counts in
      these cases ranged from 1 to 3 mitotic figures/10 HPF (mean = 1.8). Counts per 10
      HPF were significantly (p < 0.001) more for AIS cases than for controls for
      apoptotic bodies and mitotic figures. Our results indicate that apoptotic bodies,
      as well as mitotic figures, occur almost universally in AIS. Both occur
      significantly more often and in greater numbers in AIS than in nonneoplastic
      endocervical glandular epithelium. Apoptotic bodies are a consistent morphologic
      feature of AIS, and their identification may be diagnostically useful.

PMID- 9537471
TI  - Partial atrophy in prostate needle cores: another diagnostic pitfall for the
      surgical pathologist.
AB  - We have seen in consultation a variant of atrophy, which is frequently confused
      with well-differentiated adenocarcinoma of the prostate. We have designated this
      entity as partial atrophy to distinguish it from its more common counterpart of
      fully developed atrophy. Partial atrophy is defined as benign prostate glands
      with relatively scant cytoplasm, yet the glands are not fully atrophic in that
      they do not appear basophilic at low magnification. Fifty-one cases of partial
      atrophy were identified (4 from Johns Hopkins Hospital, 47 from consultation).
      Within the partial atrophy focus, irregular (crinkled) nuclei were frequent in
      23.5% and occasionally present in 33.3% of cases. Visible nucleoli were frequent
      in 25.4% of cases. Basal cells were not identifiable in 27.4% of cases or were
      hard to identify in 35.3% of cases. No intraluminal crystalloids or blue-tinged
      mucinous secretion was identified in partial atrophy. Adenocarcinoma or glands
      suspicious for cancer were present in other cores in 15.6% of cases. More fully
      developed atrophy was present in simultaneously obtained needle cores in 35.3% of
      cases. In the cases in which regular atrophy was the only coexisting condition,
      it was present within one 10x field from the partial atrophy in 22.2%, farther
      than one 10x field from the partial atrophy in 11.1%, and present in the same
      gland as the partial atrophy in 66.7%. Partial atrophy may be confused with low
      grade adenocarcinoma because of the focus of crowded glands, irregular nuclei,
      and visible nucleoli. Clues for recognizing partial atrophy include relatively
      scant cytoplasm, distinct crinkled nuclei, pale cytoplasm similar to adjacent,
      more recognizably benign glands, and association with more fully developed benign
      atrophy.

PMID- 9537472
TI  - The significance of intraluminal prostatic crystalloids in benign needle
      biopsies.
AB  - Intraluminal prostatic crystalloids (IPC) are more common in prostate cancer
      acini than in benign acini. This study was undertaken to evaluate the hypothesis
      that crystalloids seen in a benign biopsy may indicate an increased risk of a
      concomitant prostatic carcinoma. A total of 600 patients underwent more than one
      prostate biopsy. For 394 patients the results of the biopsy were either negative
      or positive for prostate cancer. After exclusion of patients whose biopsy results
      were considered negative but coded as high-grade prostatic intraepithelial
      neoplasia or were suspicious for cancer or whose slides were unavailable for
      review, 331 patients remained. Biopsy results for these patients were evaluated
      for the presence of IPC. Also, 18 completely-embedded benign prostates from
      cystoprostatectomy specimens from patients with bladder cancer were evaluated for
      the presence of IPC. Seven hundred twenty-five biopsy specimens were reviewed; 51
      (7%) contained crystalloids. Thirty-two of 634 (5%) benign biopsy specimens and
      19 of 91 (21%) prostatic carcinoma biopsy specimens contained crystalloids.
      Sixteen of 331 patients (5%) had crystalloids in the initial benign biopsy
      specimen; 6 patients subsequently were determined to have carcinoma (38%), and 10
      continued to have negative results (62%). Three hundred fifteen initial benign
      biopsies did not show crystalloids; 83 (26%) patients were subsequently diagnosed
      as having prostatic carcinoma (p = 0.238, Fisher's Exact Test, chi-square test).
      The IPC were found in 5 of 18 cystoprostatectomy prostates (28%). In this study,
      the presence of IPC on the initial biopsy specimens was not a significant risk
      factor for a subsequent diagnosis of prostate cancer. The IPC were not uncommon
      in prostates without cancer.

PMID- 9537473
TI  - High proportion of granzyme B-positive (activated) intraepithelial and lamina
      propria lymphocytes in lymphocytic gastritis.
AB  - Intraepithelial lymphocytes (IELs) and lamina propria lymphocytes (LpLs) have not
      been well studied in gastric mucosa, particularly in lymphocytic gastritis.
      Therefore, they were immunohistologically characterized with antibodies
      recognizing CD3, CD8, CD57, T cell-restricted intracellular antigen (TIA-1), and
      granzyme B (GrB). The TIA-1 labels cytotoxic granules of resting and activated T
      cells, whereas GrB decorates activated cytotoxic T cells. Thirty patients with
      celiac disease, including 20 taking gluten and 10 on a gluten-free diet, 15
      patients with nonceliac disease-associated lymphocytic gastritis, and 20 controls
      were studied. Stained cells were counted and results were given as IELs/100
      epithelial cells or percentage of lamina propria cells. Sixty percent to 90% of
      CD3+ IELs and up to 12% of lamina propria cells contained TIA-1-positive
      cytotoxic granules. The number of GrB+ IELs and LpLs was increased in
      Helicobacter pylori-positive controls (p < 0.03 vs. H pylori-negative controls)
      and celiac disease patients taking gluten (p < 0.05 vs. controls). The highest
      number of GrB+ IELs and LpLs was found in nonceliac disease-associated
      lymphocytic gastritis (p < 0.009 vs. controls, p < 0.05 vs. celiac disease). This
      study shows that a high proportion of gastric IELs and LpLs is potentially
      cytotoxic in nature. Through stimuli not yet identified, a proportion of them
      becomes activated after H pylori infestation and in lymphocytic gastritis.

PMID- 9537474
TI  - Spindle cell rhabdomyosarcoma (so-called) in adults: report of two cases with
      emphasis on differential diagnosis.
AB  - Spindle cell rhabdomyosarcoma (RMS) is a recently described variant of embryonal
      RMS that carries a relatively favorable prognosis when compared with other forms
      of RMS. To date, spindle cell RMS has been described only in children. The
      authors have identified two unusual cases occurring in adults using the following
      criteria: tumors composed mainly of fascicular, relatively monomorphic spindle
      shaped cells that show unequivocal immunohistochemical and ultrastructural
      evidence of myogenic differentiation. The tumors were identified in a 38-year-old
      woman and a 56-year-old man, arising in the cheek and left hemidiaphragm,
      respectively. Both were treated with surgical resection and chemotherapy. The
      first patient died of uncontrolled local recurrence of her tumor at 27 months
      after diagnosis, and the second died of metastatic disease at 13 months follow
      up. The tumors were composed mainly of fascicles of spindle cells with palely
      eosinophilic cytoplasm admixed diffusely with sparse polygonal, rounded, or strap
      shaped rhabdomyoblasts with brightly eosinophilic cytoplasm and with cross
      striations in the first case only. Immunostaining for muscle-related antigens
      showed staining for smooth-muscle actin (focal), pan-actin HHF-35, desmin, fast
      myosin, myoglobin, and MyoD1. Both cases were negative for S-100 protein. On
      electron microscopy, both cases showed neoplastic rhabdomyoblasts with clear-cut
      sarcomeric differentiation in many of the tumor cells. Spindle cell RMS poses
      special problems in differential diagnosis when arising in adults and should be
      distinguished from leiomyosarcoma, malignant peripheral nerve sheath tumor with
      heterologous rhabdomyoblastic differentiation (malignant Triton tumor), and
      fibrosarcoma. In view of the good prognosis afforded children with spindle cell
      RMS and in light of the chemoresponsive behavior of RMS in general, we feel that
      it is important to identify tumors that meet the criteria for spindle cell RMS
      occurring in the adult population. However, based on these two cases, it is
      possible that spindle cell RMS occurring in adults may not be associated with
      such a favorable outcome.

PMID- 9537476
TI  - Light microscopic criteria for the diagnosis of early vulvar lichen sclerosus: a
      comparison with lichen planus.
AB  - Lichen sclerosus (LS) and lichen planus (LP) are two conditions frequently
      affecting genital skin whose clinical and histologic distinction can be
      difficult. Both diseases can feature solitary genital lesions with bandlike
      lymphocytic infiltrates. We reviewed 68 cases of vulvar LS to find sections that
      contained a transition from a lichenoid interface reaction to pathognomonic LS
      (i.e., marked papillary dermal sclerosis or edema), and in these nine cases we
      studied routinely and specially stained sections, as well as sections stained
      with a panel of antisera to lymphoid antigens, and compared the findings with
      those in six cases of genital LP. We assumed that changes at the periphery of a
      lesion of LS mirror findings seen in early lesions. The features that we found
      more commonly in the inflammatory phase of LS included a psoriasiform lichenoid
      pattern (100% LS, 0% LP), basilar epidermotropism (78% LS, 0% LP), loss of
      papillary dermal elastic fibers (100% LS, 33% LP), basement membrane thickening
      (44% LS, 0% LP), and epidermal atrophy (33% LS, 0% LP). Features found more
      commonly in LP included many cytoid bodies (0% LS, 100% LP), wedge-shaped
      hypergranulosis (11% LS, 100% LP), basal squamatization (22% LS, 100% LP), and
      pointed rete ridges (11% LS, 83% LP). We did not detect any significant
      differences in the immunohistochemical features of the infiltrates. Taken
      together, these histologic features comprise light microscopic criteria for the
      diagnosis of early vulvar LS and its differentiation from LP.

PMID- 9537475
TI  - Micronodular pneumocyte hyperplasia.
AB  - Tuberous sclerosis complex (TSC) is an autosomal-dominant disorder characterized
      by mental retardation, seizures, and central nervous system and visceral
      hamartomas. Pulmonary involvement manifesting as lymphangioleiomyomatosis (LAM)
      occurs in 1% of patients (all women) with TSC. Micronodular pneumocyte
      hyperplasia also has been described as a rare pulmonary manifestation of TSC. We
      report 14 patients with micronodular pneumocyte hyperplasia (MNPH). The patients
      ranged in age from 23 to 57 years (mean 37.5). There were 12 women and 2 men.
      Nine of the patients (one man and eight women) had documented clinical
      manifestations of TSC: seven with LAM, two without LAM (including one man). Of
      the five patients who did not have TSC, three had LAM and two did not (including
      one man). Histologically, all 14 cases demonstrated multiple well-demarcated
      nodules usually measuring up to 8 mm in size, but most were 1-3 mm. The nodules
      were produced by a proliferation of enlarged cytologically benign type II
      pneumocytes, with an associated increase in alveolar macrophages and interstitial
      reticulin. Immunoperoxidase studies showed the type II pneumocytes within lesions
      to be reactive with antibodies to cytokeratin (four of four), epithelial membrane
      antigen (EMA) (five of five), and surfactant apoprotein B (8 of 10). HMB-45 was
      negative in the MNPH lesions in all nine cases studied. Follow-up was available
      in 9 of 10 living patients and ranged from 1 to 14 years (mean 6 years). Nine
      patients are alive; six are clinically stable and three have repeated
      pneumothoraces related to LAM. Four patients have died. None of the deaths were
      attributable to MNPH. MNPH appears to be a hamartomatous proliferation occurring
      most frequently in patients with tuberous sclerosis, is separable from and not a
      manifestation of LAM, has been observed to occur in men, and, like other
      hamartomas of tuberous sclerosis, does not appear to possess malignant potential.

PMID- 9537477
TI  - Cutaneous verruciform xanthoma: a report of five cases investigating the etiology
      and nature of xanthomatous cells.
AB  - Verruciform xanthoma is a rare clinicopathologic entity of uncertain etiology
      that occurs primarily in the oral mucosa. Aggregates of foam cells in the
      submucosal stroma or papillary dermis in association with verrucous epithelial
      hyperplasia are the hallmark of this lesion. Extraoral (cutaneous) occurrence of
      verruciform xanthoma is much rarer and has been reported mostly in the genital
      skin. Five cases of extraoral cutaneous verruciform xanthoma (three from the
      scrotum, one from the penis, and one from the nose) and one histologic "simulant"
      (from skin of the nose) were studied. The lesions were solitary, raised, or
      polypoid with cup-shaped craters filled with parakeratotic cells that blended
      into keratinocytes of an acanthotic and papillomatous epidermis. There was a
      neutrophilic infiltrate of varying intensity between plump parakeratotic cells
      and keratinocytes, near the surface of the epidermis. Aggregates of foam cells
      were present in the papillary dermis, which was highly vascular. A plasma cell
      predominant infiltrate was seen at the base in a bandlike fashion. Despite the
      architectural resemblance of verruciform xanthoma to verrucous mucocutaneous
      lesions related to human papillomavirus infection, it was not detected by either
      immunohistochemistry, in situ hybridization, polymerase chain reaction, or
      Southern blot analysis in any case. The foam cells were weakly positive for
      cytokeratin and for Factor XIIIa but negative for S-100 protein. The KP1 and Mac
      387 immunostain showed focal weak staining in foam cells. We postulate that a
      cascade of events pursue after initial keratinocytic damage attracting
      neutrophils, with subsequent phagocytosis of necrotic keratinocytic debris by
      dermal dendrocytes, eventually leading to the ultimate manifestation of the
      lesion as verruciform xanthoma. The etiologic agent remains elusive, but based on
      our findings, we conclude that verruciform xanthoma is most likely not a human
      papillomavirus-associated squamoproliferative lesion and that the foam cells, a
      histologic hallmark of the lesion, are most likely derived from dermal dendritic
      cells.

PMID- 9537478
TI  - Taenia crassiceps invasive cysticercosis: a new human pathogen in acquired
      immunodeficiency syndrome?
AB  - A fluctuant, painful, subcutaneous, and intermuscular tumor developed in a 38
      year-old man with severe acquired immunodeficiency syndrome (AIDS) in which
      immunodeficiency was severe. Surgery revealed lesions that formed a multilocular
      pouch embedded in deep tissues in the forearm filled with tapiocalike material
      containing a viscous fluid, granules, and cysticercilike small vesicles.
      Pathologic and parasitologic evaluation showed cysticerci embedded in a
      fibrocollagen reaction with inflammatory granulomatous reaction. Each cysticercus
      contained an invaginated scolex with two rows of small (i.e., 80 microm) and
      large (i.e., 114 microm) rostellar hooks, identical to larva of Taenia
      crassiceps. All clinical, parasitologic, and pathologic features of these
      cysticerci were very different from those of all other larval cestode (i.e.,
      Taenia solium cysticercosis, coenurosis, sparganosis, cysticercosis due to Taenia
      saginata [Cysticercus bovis], primary and secondary hydatidosis [Echinococcus
      species]). T crassiceps cysticerci usually develop in subcutis and
      pleuroperitoneal cavities of rodents, whereas the adult tapeworm is commonly
      found in the digestive tract of foxes. Biologic properties of T crassiceps
      cysticerci and epidemiologic characteristics of pandemic human immunodeficiency
      virus (HIV) could eventually indicate new potential cases of T crassiceps
      cysticercosis in humans.

PMID- 9537479
TI  - Molecular and pathologic characterization of an AIDS-related body cavity-based
      lymphoma, including ultrastructural demonstration of human herpesvirus-8: a case
      report.
AB  - Body cavity-based lymphoma, also known as primary effusion lymphoma, is a newly
      recognized acquired immunodeficiency syndrome (AIDS)-related lymphoma that has
      been linked to the Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8). To date,
      direct visualization of the virus in a clinical sample has not been demonstrated.
      We have performed an extensive clinical, histologic, immunophenotypic,
      ultrastructural, and molecular genetic correlative study on multiple tissue
      samples obtained premortem and at autopsy from an patient with AIDS with Kaposi's
      sarcoma and body cavity-based lymphomas. We demonstrate the presence of human
      herpesvirus-8 in a primary clinical sample at the ultrastructural and molecular
      level, as well as document multiple lymphomatous tumor masses at autopsy.

PMID- 9537480
TI  - Abdominal T-cell non-Hodgkin's lymphoma of the gamma/delta type in a patient with
      selective immunoglobulin A deficiency.
AB  - A 28-year-old man presented with selective immunoglobulin A deficiency and severe
      diarrhea responding to a gliadin-free diet. Biopsy samples of the small intestine
      showed dense T-cell infiltrations in the lamina propria and a slight increase of
      intraepithelial T-lymphocytes. No clonal rearrangement of the T-cell receptor c
      beta chain genes was detectable by Southern blotting. Four years later, at the
      age of 32, the patient was hospitalized again with liver failure, abdominal
      lymphadenopathy, pancytopenia, and recurrent bacterial infections. Retrospective
      polymerase chain reaction analysis of formalin-fixed tissues of the intestinal
      biopsy samples obtained 4 years earlier showed monoclonal T-cell receptor gamma
      chain gene rearrangement. Lymphoid cells of the peripheral blood showed an
      immunophenotype of CD3-positive gamma/delta T cells with a negativity for CD4 and
      CD8. A clonally rearranged T-cell receptor delta chain gene and a germline
      configuration of the c-beta chain genes was found by Southern blotting.
      Cytogenetics showed an abnormal karyotype with unbalanced translocations t(1;5)
      and t(9;13). The patient died of extensive lung infiltrations by gamma/delta T
      cells; autopsy showed a peripheral T-cell lymphoma of the gamma/delta type in the
      enlarged abdominal lymph nodes. This is the first report of an abdominal T-cell
      lymphoma of the gamma/delta type in a patient with selective immunoglobulin A
      deficiency.

PMID- 9537481
TI  - Fibrosarcoma versus cellular fibroma of the ovary.

PMID- 9537482
TI  - Concurrent renal oncocytoma and renal cell carcinoma within the same kidney:
      diagnostic implications.

PMID- 9537483
TI  - Chiral compounds in metabolism: a look in the molecular mirror.
AB  - We know that many familiar objects such as gloves, shoes and screws are non
      identical with their mirror images. The same applies to certain chemical
      compounds. These compounds show a degree of asymmetry in their structure which
      means that when looked at in a mirror, their images are not superimposable--they
      are chiral compounds and have two forms (enantiomers). Until recently biochemists
      have only been concerned with perhaps one form, other forms having been ignored
      primarily due to analytical difficulties. We now know of inborn errors of
      metabolism where one form of a pathological metabolite predominates, thus
      requiring precise enantiomeric analysis. This article provides a background to
      the field of enantiomers and their analysis as demonstrated by examples of inborn
      errors of metabolism and hints at the possible discovery of as yet unidentified
      metabolic pathways. CONCLUSION: Recent advances in the field of enantiomeric
      metabolite analysis, in particular the use of enantioselective gas chromatography
      mass spectrometry, have an increasingly important role to play, not only in the
      diagnosis of inborn errors of metabolism, but also to increase our understanding
      of normal physiological processes.

PMID- 9537484
TI  - Charter on continuing medical education in paediatrics in the European Union.
      Confederation of European Specialists in Paediatrics Working Group on Continuing
      Medical Education.

PMID- 9537485
TI  - Effects of cardiopulmonary bypass and inhaled nitric oxide on platelets in
      children with congenital heart defects.
AB  - Nitric oxide (NO) reduces platelet aggregation in vitro. However, repeated
      measurements of platelet aggregation in infants and small children are impossible
      due to the large blood samples required. Instead, the expression of different
      platelet receptors mediating platelet adhesion (CD 36 and CD 42b), activation (CD
      42b and CD 61) and aggregation (CD 41a) was measured repeatedly by flow
      cytometry. First, the expression of platelet receptors was quantified in platelet
      suspensions of 20 healthy volunteers after incubation with different
      concentrations of NO (0, 25, 100 and 640 ppm) and compared to changes in platelet
      aggregation and intrathrombocytic cGMP levels. It was then studied in 21 infants
      and children before, during and up to 3 days after cardiopulmonary bypass
      surgery. Seven of these patients required NO inhalation postoperatively. The in
      vitro experiments showed a reduced expression of the CD 41a, CD 42b and CD 61
      receptors with increasing doses of NO, predominantly affecting the CD 41a
      receptor (-11% at 100 ppm and -20% at 640 ppm). This significant effect is in
      keeping with the observed NO-induced inhibition of platelet aggregation (-44% at
      100 ppm) and the rise in platelet cGMP levels (+69% at 100 ppm). In patients
      without inhaled NO, the expression of CD 41a was slightly attenuated during
      cardiopulmonary bypass surgery (-15%) but increased significantly afterwards (2
      h: +31%, 1st day: +129%, 2nd day: +120%, 3rd day: +111%). Comparable results were
      obtained regarding the other adhesion molecules CD 36, CD 42b and CD 61. In
      patients with inhaled NO the same pattern was observed and analysis of variance
      did not reveal any significant difference between both groups of patients.
      CONCLUSIONS: NO (> or = 100 ppm) decreases the expression of different platelet
      adhesion molecules and platelet aggregation, presumably via an increase in
      intracellular cGMP. However, due to the low dose range used in the clinical
      setting (1-40 ppm) this is clinically not relevant. Immediately after
      cardiopulmonary bypass surgery the expression of these adhesion molecules is
      reduced, but recovers on the 1st postoperative day.

PMID- 9537486
TI  - Does the long-term clinical course of type I diabetes mellitus differ in patients
      with prepubertal and pubertal onset? Results of the Berlin Retinopathy Study.
AB  - The objective of the present study was to investigate potential differences at
      presentation of type I diabetes and during its long-term clinical course in
      children and adolescents with prepubertal and pubertal manifestation. Clinical,
      immunological and biochemical characteristics at diabetes onset of 453 patients
      (320 prepubertal, 133 pubertal; median age at manifestation 7.1 years (0.7-13.9)
      and 13.1 years (9.2-17.6), respectively) were evaluated. Glycaemic control and
      exogenous insulin requirements were followed prospectively, with a median follow
      up of 9.4 years. At the onset of the disease no differences concerning the degree
      of metabolic decompensation, impairment of somatic health, and islet cell
      antibody status could be detected between the groups, except for a smaller body
      weight loss in pubertal patients (P=0.011). The duration of partial remission
      (insulin requirements <0.5 IU/kg body weight/day) was unrelated to age or
      pubertal status at onset. It was found to be longer in boys than in girls in the
      total cohort (median duration: 279 vs 215 days, P = 0.0071). Despite an absence
      of differences during the early course of the disease, glycaemic control was
      better, and daily insulin doses were significantly lower in patients with
      pubertal onset, after 6 years of diabetes. CONCLUSION: Adolescents with a
      pubertal onset of type I diabetes have a more benign long-term course of the
      disease demonstrating better glycaemic control and lower insulin requirements,
      although the presentation of the disease at onset and its course during the first
      6 years are not different from those of children with a prepubertal manifestation
      of diabetes.

PMID- 9537487
TI  - Immunogenicity and reactogenicity of a Haemophilus influenzae type b tetanus
      conjugate vaccine when administered separately or mixed with concomitant
      diphtheria-tetanus-toxoid and acellular pertussis vaccine for primary and for
      booster immunizations.
AB  - With an increasing number of new vaccines available for routine childhood
      immunization, combination vaccines are needed in order to maintain or achieve a
      high compliance with recommended immunization programmes. In a prospective,
      randomized, comparative, multi-centre study, 822 healthy infants were enrolled to
      receive three doses of either a candidate or a commercially available Haemophilus
      influenzae type b (Hib) vaccine concomitantly with diphtheria-, tetanus-
      acellular pertussis (DTaP) vaccine. Study subjects were randomly allocated to one
      of the following groups: (1) separate, or (2) mixed injection of DTaP and
      candidate Hib vaccine, or (3) separate injection of DTaP and commercial Hib
      vaccine. One year later the first 189 study subjects received either separate or
      mixed injections of the same Hib and DTaP vaccines as booster doses. Evaluation
      of reactogenicity was based on diary cards completed by parents. Immunogenicity
      was documented by measuring IgG antibody concentrations in serum samples taken
      before and 4 weeks after primary and booster vaccination. No serious adverse
      events occurred and most local and systemic reactions were mild to moderate.
      Booster doses were more reactogenic than primary doses with all groups. Antibody
      concentrations against pertussis antigens were similar to those seen with DTaP
      alone. All but one subject had protective antibody concentrations against
      diphtheria and tetanus. Primary immune response to the Hib vaccine was
      significantly lower in the group receiving the mixed Hib-DTaP vaccine, however, >
      or = 95% of vaccinees had anti-Hib antibody concentrations > or = 0.15 microg/ml
      and there was a marked booster response (> 100-fold) in all groups. CONCLUSIONS:
      Mixing DTaP and Hib vaccines for primary immunization caused a decrease in anti
      Hib antibody response, although after primary immunization as after booster
      doses, all subjects showed antibody concentrations considered to be protective
      for invasive Hib disease. Mixing of the vaccines did not result in increased
      reactogenicity.

PMID- 9537488
TI  - International variation in the management of infants hospitalized with
      respiratory syncytial virus. International RSV Study Group.
AB  - Respiratory syncytial virus (RSV) is a frequent cause of hospitalization among
      infants. To compare patient management in Europe, the United States, and
      Australia, we analyzed the charts of 1,563 pediatric patients hospitalized with
      laboratory-confirmed RSV lower respiratory infections during recent RSV seasons.
      Half of patients had been seen initially as outpatients. Median duration of
      hospitalization was 4 days in Australia, Finland, the United Kingdom, and the
      United States, and 8 or 9 days in Belgium, France, Germany, Italy, and the
      Netherlands. In a linear regression model that included clinical findings,
      underlying conditions, prematurity, and age, the leading variable associated with
      length of stay was "hospitalization in continental Europe". This geographic
      factor conferred a 1.8-fold longer stay (95% CI: 1.7-1.9) than hospitalization
      elsewhere. Utilization of nine supportive therapies for RSV varied widely among
      hospitals, even within the same country. The individual hospital was strongly
      associated with the use of every therapy studied, independent of patient
      characteristics and clinical status. CONCLUSION: Management of RSV patients
      varies markedly by country and hospital. Multicenter RSV trials that measure
      length of stay should standardize criteria for "readiness for discharge". It may
      be appropriate to limit international trials to countries with similar median
      stays for RSV. Variability within multicenter trials could be further controlled
      by standardizing the use of other therapies and the diagnosis of complications.

PMID- 9537489
TI  - Antibodies to group B streptococci in neonates and infants.
AB  - Invasive group B streptococcal (GBS) infections are common in neonates but are
      rare after the 1st month of life. It is not known why GBS infections have this
      age distribution which differs from that of invasive infections caused by other
      encapsulated bacteria. The aim of this study was to test the possibility that
      serum antibodies against the GBS capsular polysaccharides (CPS) are acquired
      during the first months of life thereby preventing infections after the neonatal
      period. Cord sera were collected from 321 healthy term newborns. A second blood
      sample was collected at 2, 4, 8, 13 or 26 weeks of age. IgG CPS antibodies
      (measured by ELISA) against serotypes Ia, II and III were present in 98%-100% of
      all cord sera and decreased continuously during the first 6 months of life. No
      IgM antibodies against serotype III CPS were present in cord sera. Only 16%-17%
      of the children acquired IgM antibodies against serotype III CPS at 3 and 6
      months of age. CONCLUSION: Early acquisition of IgG or IgM antibodies against CPS
      of the most common GBS serotypes was not demonstrated and cannot explain the rare
      occurrence of invasive GBS infections in children after the 1st month of life.

PMID- 9537490
TI  - Partial 3-methylcrotonyl-CoA carboxylase deficiency in an infant with fatal
      outcome due to progressive respiratory failure.
AB  - Isolated partial 3-methylcrotonyl-CoA carboxylase (MCC) deficiency has been
      described to be the cause for a distinct relatively mild clinical picture in a
      single patient. We describe another patient with isolated partial MCC deficiency
      who suffered from failure to thrive, muscular hypotonia and progressive
      respiratory insufficiency with fatal outcome at the age of 6.5 months. MCC
      deficiency was suspected at 3 months of age on the basis of mildly elevated
      urinary excretion of 3-hydroxyisovaleric acid and 3-methylcrotonylglycine and
      confirmed by enzyme analysis in lymphocyte and fibroblast homogenates. Residual
      MCC activity in lymphocytes was 25% of the mean normal value. Residual activity
      in fibroblasts was lower than in lymphocytes (3.8% of mean normal) and not
      significantly different from that in patients with complete MCC deficiency.
      However, the residual incorporation of 14C-isovalerate into macromolecules in
      intact fibroblasts, was clearly higher (28% of mean normal) than in fibroblasts
      with complete MCC deficiency (<4%). In both patients with partial deficiency the
      residual MCC activity was higher in lymphocytes than in fibroblasts. Clinical
      symptoms and signs in our patient attributable to MCC deficiency include muscular
      hypotonia, failure to thrive (already present at birth), progressive respiratory
      failure due to diaphragmatic paresis and a moderate brain atrophy. The clinical
      presentation was more severe than in many patients with complete MCC deficiency.
      Dietary therapy was biochemically effective as shown by normalization of organic
      acid excretion, however, had no effect on the CNS symptoms. CONCLUSION: We
      speculate that the severity of the disease could be related primarily to
      deficiency of MCC activity in the brain. Variable MCC activity among various
      organs may explain the peculiar clinical picture in this patient.

PMID- 9537491
TI  - Neonatal risk factors and risk scores including auditory evoked responses.
AB  - In a prospective study, 81 preterm infants and 25 healthy term infants were
      neurologically and neurophysiologically evaluated in the neonatal period. At 5-7
      years of age the neurodevelopmental outcome was assessed. The validity and
      predictive value of the Neonatal Neurological Inventory (NNI) and the
      Neurobiological Risk Score (NBRS), including an additional gestational age factor
      (GAF) and an auditory evoked response factor (AERF) were assessed. Three of the
      53 surviving preterm infants showed major neurological abnormalities at 5-7
      years. Five infants showed neuropsychological abnormalities and 12 infants showed
      both neurological and neuropsychological abnormalities. An important subgroup of
      preterm infants could be identified as high-risk using the NNI and NBRS. The low
      sensitivity and negative predictive value resulted in a number of false-negative
      results. Logistic regression showed that intraventricular haemorrhage (IVH) and
      bilirubin levels contributed highly to the prediction of neurological outcome.
      For neuropsychological outcome these factors were IVH and assisted ventilation.
      Addition of the GAF and AERF as separate items to the NBRS did not affect the
      predictive power. Combined addition of the GAF and AERF showed improvement of
      both validity and predictive value. CONCLUSION: This study shows that IVH,
      bilirubin and assisted ventilation contribute most to the validity and predictive
      value of the NBRS. Furthermore, regarding neurological outcome addition of a GAF
      in combination with an AERF resulted in a substantial improvement of the validity
      and predictive value. The shortcomings of the current neonatal risk scores
      require a careful interpretation of clinical perinatal data regarding the
      prediction of neurodevelopmental outcome in preterm infants.

PMID- 9537492
TI  - Thymic cyst haemorrhages and transient cholestasis in a 4-week-old infant.
AB  - We report a 4-week-old boy with acute respiratory distress, due to massive
      haemorrhages in multiple thymic cysts. A right hemithymectomy was performed
      because of mechanical obstruction of the trachea by the cysts. The origin of the
      multilocular thymic cysts remained unclear. Most likely, these haemorrhages were
      caused by vitamin K deficiency, although the infant received vitamin K
      prophylaxis. In addition, he developed transient cholestasis, but the aetiology
      remained unclear. It is postulated that massive haemorrhages in thymic cysts
      produce large amounts of bilirubin, causing sludging of bile excretions in the
      liver. Four weeks after the operation, all laboratory findings were normal and 6
      months after the operation the boy is still healthy. CONCLUSION: This case report
      shows that respiratory distress in an infant can be caused by multiple
      haemorrhages in multilocular thymic cysts.

PMID- 9537493
TI  - End-stage renal failure in children younger than 6 years: renal transplantation
      is the therapy of choice.
AB  - Between 1975 and 1994, 46 children under 6 years of age received a total of 52
      renal transplants. Obstructive uropathy and dysplasia accounted for most causes
      of terminal renal failure (17 and 12 cases respectively). Four patients required
      a second, 1 patient a third transplantation. Cadaveric organs were used on 33
      occasions; 19 patients received a living-related donor kidney. Immunosuppression
      was performed with azathioprine in 5, with cyclosporine A in 21 and combined
      azathioprine/cyclosporine therapy in 20 cases. After 1 year, graft survival was
      81%, and after 5 years 78%. Creatinine clearance declined slightly between 1 and
      5 years from 69 to 56 ml/min per 1.73 m2. Main causes of graft failure were
      thrombotic complications in 6 cases and death with functioning graft in 5 cases.
      Graft thrombosis occurred only in grafts from young donors under the age of 7
      years and after vascular anastomosis to the iliac vessels. Only two transplants
      were lost in rejection episodes. Patient survival was 94% after 1 and 90% after 5
      years. Two patients died due to septiacemia, 1 died of a ruptured aortic
      aneurysm, 1 of cerebral ischaemia and 1 suddenly of unknown cause. Patient and
      graft survival was not different compared with 204 patients aged 6-16 years who
      received a renal transplantation during the same time period at our institution.
      After transplantation the patients receiving cyclosporine A showed a marked catch
      up growth in the 1st year. The median standard deviation score (SDS) of body
      length improved from -2.63 to -1.39 standard deviations. CONCLUSION: Renal
      transplantation is the treatment of choice in end-stage renal failure in children
      under 6 years.

PMID- 9537494
TI  - Rapidly progressive glomerulonephritis in a boy with hypocomplementaemic
      urticarial vasculitis.
AB  - The present paper reports the fourth case of hypocomplementaemic urticarial
      vasculitis in a child. We describe a boy who, after many years of arthritis,
      urticaria, eye inflammation and hypocomplementaemia, developed rapidly
      progressive glomerulonephritis which was completely reversed by immunosuppressive
      therapy. CONCLUSION: Only three paediatric patients with hypocomplementaemic
      urticarial vasculitis have been described. Severe renal involvement was
      reversible with early appropriate treatment.

PMID- 9537495
TI  - Effects of heavy maternal smoking on intrauterine growth patterns in sudden
      infant death victims and surviving infants.
AB  - Sudden infant death (SID) is associated with both intrauterine growth retardation
      and maternal smoking during pregnancy. Here, we investigated if the statistical
      association between maternal smoking and SID is direct or mediated through the
      well-known growth retarding effects of heavy maternal smoking on the
      fetoplacental unit. We analysed data from a population-based prospective cohort
      study (181 cases, total newborn population 227,791 births) within the Westphalian
      Perinatal Inquiry in Germany between 1990 and 1994. SID victims whose mothers did
      not smoke had a normal mean birth weight (mean 3415.5 vs 3431.5 g), length (mean
      51.46 vs 51.66 cm), and body mass index (BMI) (mean 12.8 vs 12.8 kg/m2) when
      compared to surviving children. In contrast, SID victims of mothers who smoked
      heavily (> ten cigarettes per day) had a significantly lower birth weight
      (2911.21 g vs 3148.34 g), length (48.98 vs 50.39 cm), and BMI (11.8 vs 12.4
      kg/m2) when compared to surviving children whose mothers smoked heavily.
      Stratification for gestational age revealed that these differences are mainly
      caused by preterm SID infants. CONCLUSION: The statistical association between
      maternal smoking and SID mainly results from effects of tobacco smoke on the
      fetoplacental unit which, in later SID victims, appears to be more susceptible to
      the growth retarding effects of cigarette smoking.

PMID- 9537496
TI  - Airway obstruction by a child's pacifier--could flange design be safer?
AB  - The use of pacifiers (dummies or soothers) for infants is prevalent. Rare
      episodes of an adverse consequence must be taken seriously. We report a case of
      aspiration of a pacifier by a 6-month-old baby. Nine similar cases were found in
      the literature since 1966. The details of these cases are outlined and changes to
      flange design proposed ahead of a new European Union Standard document.
      CONCLUSION: Pacifier ventilation holes are essential, flanges should have a
      minimum horizontal and vertical diameter of 43 mm. Rings should be attached to
      the flange to facilitate removal if aspirated.

PMID- 9537497
TI  - An 8-year-old boy with renal failure, nephrolithiasis and bone pain.

PMID- 9537498
TI  - Whole body calcium content in term and preterm neonates.

PMID- 9537499
TI  - Pain relief by carbamazepine in mercury poisoning.

PMID- 9537500
TI  - Increased prevalence of factor V Leiden mutation in neonatal intracranial
      haemorrhage.

PMID- 9537501
TI  - Intravenous pamidronate treatment in osteogenesis imperfecta.

PMID- 9537502
TI  - Vitamin D metabolites in patients with coeliac disease.

PMID- 9537503
TI  - Rapid decline of serum leptin levels in healthy neonates after birth.

PMID- 9537504
TI  - Comparative molecular analysis of Na+/H+ exchangers: a unified model for Na+/H+
      antiport?
AB  - Despite 30 years of study on Na+/H+ exchange, the molecular mechanisms of
      antiport remain obscure. Most challenging, the identity of amino acids involved
      in binding transported cations is still unknown. We review data examining the
      identity of residues that are involved in cation binding and translocation of
      prokaryotic and eukaryotic Na+/H+ antiporters. Several polar residues
      specifically distributed within or immediately adjacent to membrane spanning
      regions are implicated as being important. These key amino acids are conserved in
      prokaryotes and in some lower eukaryotic forms of the Na+/ H+ antiporter, despite
      their being dispersed throughout the protein and despite an overall low
      similarity in the linear sequence of these Na+/H+ antiporters. We suggest that
      this conservation of isolated residues (together with distances between them)
      reflects a general physicochemical mechanism of cation binding by exchangers. The
      binding could be based on coordination of the substrate cation by a crown ether
      like cluster of polar atomic groups amino acids, as has been hypothesized by
      Boyer. Traditional screening for the extended, highly conserved linear protein
      sequences might not be applicable when searching for functional domains of ion
      transporters. Three-dimensional constellations of polar residues (3D-motifs) may
      be evolutionary conserved rather than linear primary sequence.

PMID- 9537505
TI  - Structure of the mouse klotho gene and its two transcripts encoding membrane and
      secreted protein.
AB  - We previously established a novel mouse model for human aging and identified the
      genetic foundation responsible for it. A defect in expression of a novel gene,
      termed klotho (kl), leads to a syndrome resembling human aging in mice. The kl
      gene encodes a single-pass membrane protein whose extracellular domain carries
      homology to beta-glucosidases. In this report, we present the entire mouse kl
      gene organization. The mouse kl gene spans about 50 kilobases and consists of
      five exons. The promoter region lacks a TATA-box and contains four potential
      binding sites for SP1. We further show that two kl gene transcripts encoding
      membrane or secreted protein are generated through alternative transcriptional
      termination. These findings provide fundamental information for further study of
      the kl gene which may regulate aging in vivo.

PMID- 9537506
TI  - Two genes, COL4A3 and COL4A4 coding for the human alpha3(IV) and alpha4(IV)
      collagen chains are arranged head-to-head on chromosome 2q36.
AB  - We first isolated and characterized genomic DNA fragments that cover the 5'
      flanking sequences of COL4A3 and COL4A4 encoding the human basement membrane
      alpha3(IV) and alpha4(IV) collagen chains, respectively. Nucleotide sequence
      analysis indicated that the two genes are arranged head-to-head. To determine
      transcription start site for COL4A4 gene, we performed RACE and RNase protection
      assays, indicating that there are two alternative transcripts presumably derived
      from two different promoters. Interestingly, one transcription start site (from
      exon 1') of COL4A4 is only 5 bp away from the reported transcription start site
      of COL4A3, whereas the other transcript (from exon 1) starts 373 nucleotides
      downstream from the first one, generating the two kinds of transcripts that
      differ in the 5' UTR regions. Expression of these two transcripts appears tissue
      specific; exon 1 transcript was expressed predominantly in epithelial cells,
      while exon 1' transcript showed rather ubiquitous and low expression. The
      nucleotide sequence of the promoter region is composed of dense CpG
      dinucleotides, GC boxes, CTC boxes and a CCAAT box but no TATA box. These results
      provide information to delineate the promoter activity for the tissue-specific
      expression of the six type IV collagen genes and basement membrane assembly in
      different tissues and organs.

PMID- 9537507
TI  - Activation of a plant plasma membrane Ca2+ channel by TGalpha1, a heterotrimeric
      G protein alpha-subunit homologue.
AB  - Wild-type and GTPase-deficient recombinant TGalpha1 were used along patch-clamp
      techniques to study the role of heterotrimeric G proteins in the regulation of
      the hyperpolarized active tomato plasma membrane Ca2+ channel. Recombinant alpha
      subunits induced an increase in channel activity as shown by the increase in
      channel events and the mean open probability of the channel. Our results suggest
      a membrane-delimited pathway involving heterotrimeric G proteins in Ca2+ channel
      activation.

PMID- 9537508
TI  - Identification of a lipoxygenase inhibitor in A431 cells as a phospholipid
      hydroperoxide glutathione peroxidase.
AB  - An endogenous lipoxygenase inhibitor, purified from the cytosol of human
      epidermoid carcinoma A431 cells, was analyzed by N-terminal microsequencing and
      mass spectrometric analysis. The inhibitor was purified by SDS-PAGE, then
      subjected to in-gel CNBr cleavage and trypsin digestion. The N-terminal sequence
      data obtained from a 6-8 kDa band of in-gel CNBr cleavage and the three isolated
      peptides of in-gel trypsin digestion, and the C-terminal peptide sequence from
      matrix-assisted laser desorption ionization mass spectrometry matched the
      sequence of human phospholipid hydroperoxide glutathione peroxidase. The purified
      inhibitor exhibited peroxidase activity using phosphatidylcholine hydroperoxides
      as the substrate. We therefore concluded that the lipoxygenase inhibitor present
      in A431 cells was a phospholipid hydroperoxide glutathione peroxidase.

PMID- 9537509
TI  - Interaction of Oct-1 and automodification domain of poly(ADP-ribose) synthetase.
AB  - We isolated several clones from a matchmaker two-hybrid system human lymphocyte
      cDNA library using an automodification domain of poly(ADP-ribose) synthetase
      (PARS) as a probe. A DNA sequence (approximately 1 kbp) of the clone was
      identical to part of the Oct-1 DNA sequence. We then constructed either a His
      tagged or GST fusion protein of the inserted cDNA from the clone and the fusion
      protein was shown to interact with PARS by far-Western blot analysis and co
      precipitation with affinity resin. Furthermore, the His-tagged Oct-1/POU-homeo
      fusion protein interacted weakly with the octamer motif of the DRa promoter and
      the addition of PARS fusion protein greatly increased the DNA binding activity.
      These results suggest that PARS interacts with Oct-1 and stabilizes the binding
      of Oct-1 to the octamer motif.

PMID- 9537510
TI  - Involvement of calmodulin in the activation of store-operated Ca2+ entry in rat
      hepatocytes.
AB  - The possible participation of calmodulin in the activation of store-operated Ca2+
      entry (SOC) in single rat hepatocytes was investigated
      microspectrofluorimetrically. SOC was triggered after discharging intracellular
      Ca2+ stores using the endoplasmic reticulum Ca2+-ATPase inhibitor thapsigargin in
      the absence of external Ca2+. Re-admission of bath Ca2+ caused a rapid and
      pronounced Ca2+ entry. The calmodulin antagonists calmidazolium or CGS 9343B
      applied before the thapsigargin treatment inhibited SOC, whereas they were
      ineffective when added after the thapsigargin-induced Ca2+ transient. This study
      suggests that activation of calmodulin after the elevation of cytosolic Ca2+
      associated with the emptying of Ca2+ stores is involved in the triggering of SOC
      in hepatocytes.

PMID- 9537511
TI  - Molecular cloning and tissue expression of porcine beta-defensin-1.
AB  - Beta-defensins constitute an emerging family of cysteine-rich antimicrobial
      peptides, which are particularly prominent at mucosal epithelial sites in
      mammals. Here we report the identification of a novel beta-defensin from porcine
      tissues, porcine beta-defensin-1 (pBD-1). The cDNA sequence of pBD-1 encoded a 64
      amino acid prepro-peptide, which contained the beta-defensin consensus sequence
      of six invariantly spaced cysteine residues. Northern blot analysis showed that
      pBD-1 was expressed abundantly in tongue epithelia and that the expression was
      regulated developmentally. Using RT-PCR, pBD-1 mRNA was detected throughout the
      respiratory and digestive tracts and also in thymus, spleen, lymph node, brain,
      liver, kidney, urinary bladder, testis, skin, heart, muscle, bone marrow,
      peripheral blood neutrophils, alveolar macrophages, and umbilical cord. The wide
      expression of pBD-1 suggests that this endogenous peptide antibiotic may
      contribute to both mucosal and systemic host defenses in pigs, which may have
      implications for the use of porcine tissues and organs in xenotransplantation.

PMID- 9537513
TI  - Asp477 is a determinant of the enantioselectivity in yeast transketolase.
AB  - The conserved residue Asp477 in yeast transketolase is located in the substrate
      channel of the enzyme and forms a hydrogen bond with the C2-hydroxyl group of the
      acceptor substrate. The significance of this interaction for the recognition of
      the preferred acceptor substrates, D-alpha-hydroxyaldehydes was investigated by
      site-directed mutagenesis. In the wild-type enzyme the kcat/KM values are by
      three to four orders of magnitude lower for 2-deoxyaldoses or substrates with L
      configuration at the C2-atom. In the Asp477 Ala mutant, the kcat/KM values for D
      alpha-hydroxyaldehydes are decreased by a thousandfold, while the kcat/KM values
      for substrates with L-configuration or 2-deoxyaldoses are similar to wild-type
      enzyme. These results indicate that Asp477 is involved in determining the
      enantioselectivity of transketolase.

PMID- 9537512
TI  - TRUNDD, a new member of the TRAIL receptor family that antagonizes TRAIL
      signalling.
AB  - TRAIL/Apo-2L induces rapid apoptosis of a variety of tumor cell lines. A family
      of tumor necrosis factor receptor-related molecules have been identified as
      receptors for TRAIL. Herein, we report the identification of another member of
      the TRAIL receptor family, TRUNDD (TRAIL receptor with a truncated death domain).
      The TRUNDD transcript was detected in multiple human tissues. TRUNDD is highly
      homologous to all known TRAIL receptors and has an extracellular TRAIL-binding
      domain but lacks a functional intracellular death domain and does not induce
      apoptosis. Consistent with an inhibitory role, ectopic expression of TRUNDD
      attenuated TRAIL-induced apoptosis in mammalian cells.

PMID- 9537514
TI  - Identification of rhodopsin in the pigeon deep brain.
AB  - We detected rhodopsin gene expression in the pigeon lateral septum, a
      photosensitive deep brain region that is responsible for the photoperiodic
      gonadal response. The nucleotide sequence of the deep brain rhodopsin cDNA clone
      exactly matched that of the retinal one, indicating that a single rhodopsin gene
      is transcribed in the two tissues. Immunohistochemical analysis localized
      rhodopsin in the cerebrospinal fluid-contacting neurons, which have been assumed
      to be photoreceptive cells in the deep brain. Pigeon rhodopsin seems to play dual
      important roles in the visual and non-visual systems, the latter of which
      contributes to the photoperiodic response.

PMID- 9537515
TI  - Folding and cell surface expression of the vasopressin V2 receptor: requirement
      of the intracellular C-terminus.
AB  - We characterized truncations of the human vasopressin V2 receptor to determine
      the role of the intracellular C-terminus (comprising about 44 amino acids) in
      receptor function and cell surface expression. In contrast to the wild-type
      receptor, the naturally occurring mutant R337X failed to confer specific [3H]AVP
      binding to transfected cells. In addition, no vasopressin-sensitive adenylyl
      cyclase was detectable in membrane preparations of these cells. Laser scanning
      microscopy revealed that c-myc epitope- or green fluorescent protein-tagged R337X
      mutant receptors were retained within the endoplasmic reticulum. Increasing the
      number of C-terminal residues (truncations after codons 348, 354 and 356)
      restored G protein coupling, but revealed a length-dependent reduction of cell
      surface expression. Replacement of positively charged residues within the C
      terminus by glutamine residues also decreased cell surface expression. A chimeric
      V2 receptor with the C-terminus replaced by that of the beta2-adrenergic receptor
      did not bind [3H]AVP and was retained within the cell. These data suggest that
      residues in the N-terminal part of the C-terminus are necessary for correct
      folding and that C-terminal residues are important for efficient cell surface
      expression.

PMID- 9537516
TI  - Cloning and characterization of MUPP1, a novel PDZ domain protein.
AB  - Using the yeast two-hybrid system we isolated a cDNA clone encoding a novel
      protein interacting with the C-terminal domain of the 5-HT2C receptor. The
      protein, named MUPP1 (multi-PDZ-domain protein), contains thirteen PDZ domains
      and no obvious catalytic domain; it is related to hINADL and a putative C.
      elegans polypeptide referred to as C52A11.4 containing six or ten PDZ domains,
      respectively. Domains highly similar to those of MUPP1 are arrayed in the same
      order in all three proteins. The MUPP1 gene is localized on human chromosome 9p24
      p22. Transcripts encoding MUPP1 are abundant in the brain as well as in several
      peripheral organs.

PMID- 9537517
TI  - A deep brain photoreceptive molecule in the toad hypothalamus.
AB  - We have isolated a cDNA clone encoding a deep brain photoreceptive molecule from
      the hypothalamic cDNA library of the toad, Bufo japonicus. The deduced amino acid
      sequence showed the highest similarity to that of pinopsin (75-76%) among
      vertebrate retinal opsins, indicating the expression of toad pinopsin in the deep
      brain. Antibodies raised against the C-terminal tail of toad pinopsin stained
      cell bodies and the knob-like structures of the cerebrospinal fluid-contacting
      neurons in the anterior preoptic nucleus. This region is known to play an
      important role in breeding behavior, suggesting that toad pinopsin acts as a
      photosensor for the photoperiodic gonadal response.

PMID- 9537518
TI  - Cloning, expression analysis and chromosomal localization of the human nuclear
      receptor gene GCNF.
AB  - Germ cell nuclear factor (GCNF) is an orphan member of the nuclear receptor gene
      superfamily. We report the cloning of a cDNA encoding a new variant of human GCNF
      from human testis and its expression analysis. Southern blot analysis of the
      human genomic DNA indicates that the GCNF gene is not closely related to other
      members within the nuclear receptor superfamily. Chromosomal localization of the
      GCNF gene shows that the gene is located on chromosome 9 at the locus q33-34.1.
      In situ hybridization analysis of GCNF expression in the testis shows that human
      GCNF is expressed exclusively in germ cells.

PMID- 9537519
TI  - Fuel oxidation in skeletal muscle is increased by nitric oxide/cGMP--evidence for
      involvement of cGMP-dependent protein kinase.
AB  - The cyclic guanosine-3',5'-monophosphate (cGMP) analogue, 8-bromo-cGMP (1 mM),
      increased glucose oxidation in isolated soleus muscle. The nitric oxide (NO)
      donor, sodium nitroprusside (SNP) (15 mM), increased glucose, pyruvate, palmitate
      and leucine oxidation. Removal of extracellular Ca2+ did not affect SNP
      stimulated glucose oxidation (or other glucose utilization parameters), thus
      eliminating the influx of Ca2+ as a mechanism for the increases. The guanylate
      cyclase inhibitor, LY-83583 (10 microM), inhibited SNP-stimulated palmitate
      oxidation and activation of cGMP-dependent protein kinase (PKG). Activation of
      PKG might supersede any inhibitory effects of NO on respiration to stimulate
      metabolic fuel oxidation in skeletal muscle.

PMID- 9537520
TI  - Vitronectin-dependent invasion of epithelial cells by Neisseria gonorrhoeae
      involves alpha(v) integrin receptors.
AB  - Binding of vitronectin (VN) to Neisseria gonorrhoeae expressing the heparan
      sulfate proteoglycan (HSPG) specific Opa50 protein was recently shown to trigger
      bacterial internalization into distinct epithelial cell lines. We have
      investigated the role of VN-binding integrin receptors and protein kinase C (PKC)
      in VN-triggered bacterial uptake. Blocking integrin function by RGDS peptides or
      by antibodies specific to alpha(v)beta5 or alpha(v)beta3 resulted in an
      abrogation of VN-triggered bacterial internalization. Moreover, inhibitors of PKC
      were found to block VN-triggered uptake. The essential role of alpha(v) integrins
      and the presumable involvement of PKC in VN-triggered gonococcal uptake are
      discussed.

PMID- 9537521
TI  - Structure of the pheromone peptide of the Staphylococcus epidermidis agr system.
AB  - The agr quorum-sensing system is responsible for the regulation of several
      virulence factors in staphylococci, with an extracellular pheromone peptide as
      signalling molecule. By monitoring the biological activity of synthetic peptides,
      it could be demonstrated that the pheromone of the agr system in Staphylococcus
      epidermidis is an octapeptide containing a thiolester linkage between the central
      cysteine and the C-terminal carboxyl group. The peptide was active at nanomolar
      concentrations. The N-terminus of the peptide pheromone, which is encoded as part
      of a protein precursor, proved to be crucial for biological activity.

PMID- 9537522
TI  - Specific association of photosystem II and light-harvesting complex II in
      partially solubilized photosystem II membranes.
AB  - In this study, we report the structural characterization of photosystem II
      complexes obtained from partially solubilized photosystem II membranes. Direct
      observation by electron microscopy, within a few minutes after a mild disruption
      of the membranes with the detergent n-dodecyl-alpha,D-maltoside, revealed the
      presence of several large supramolecular complexes. Images of these complexes
      were subjected to multivariate statistical analysis and classification
      procedures, resolving a new complex consisting of the previously characterized
      dimeric supercomplex of photosystem II and light-harvesting complex II [Boekema
      et al., Proc. Natl. Acad. Sci. USA 92 (1995) 175-179] and two additional,
      symmetrically organized protein masses each containing a second type of trimeric
      light-harvesting II complex. We conclude that large and labile integral membrane
      proteins, such as photosystem II, can be quickly structurally characterized
      without extensive purification.

PMID- 9537524
TI  - Sec/SRP-independent insertion of two thylakoid membrane proteins bearing
      cleavable signal peptides.
AB  - Two imported thylakoid membrane proteins, PSII-X and PSII-W, are synthesised with
      cleavable N-terminal signal peptides that closely resemble those of Sec-dependent
      lumenal proteins. In this report we have reconstituted the insertion of pre-PSII
      X and pre-PSII-W into isolated thylakoids. We show that insertion does not
      require either nucleoside triphosphates or stromal extracts, both of which are
      required for Sec- and signal recognition particle (SRP)-dependent targeting
      mechanisms. Insertion is furthermore unaffected by protease treatments that
      destroy the known protein translocation apparatus in the thylakoid membrane. We
      conclude that these membrane proteins are inserted by an unusual Sec/SRP
      independent mechanism that probably resembles that used by CFoII, and we discuss
      possible parallels with the biogenesis of phage M13 procoat.

PMID- 9537523
TI  - ABI1 of Arabidopsis is a protein serine/threonine phosphatase highly regulated by
      the proton and magnesium ion concentration.
AB  - The plant hormone abscisic acid (ABA) mediates various responses such as stomatal
      closure, maintenance of seed dormancy, and inhibition of plant growth. All three
      responses are regulated by the ABI1 gene product. The ABI1 protein (ABI1p) has
      been characterized as a protein serine/threonine phosphatase of type 2C that is
      highly affected in its activity by changes in the proton and magnesium ion
      concentrations. In the ABA-insensitive mutant abi1 of Arabidopsis thaliana a
      single amino acid exchange in the primary structure results in both a dominant
      insensitive phenotype and a strongly reduced protein phosphatase activity in
      vitro by possibly impairing metal ion coordination.

PMID- 9537525
TI  - Sulfitolysis and thioredoxin-dependent reduction reveal the presence of a
      structural disulfide bridge in spinach chloroplast fructose-1,6-bisphosphatase.
AB  - A significant difference between cytosolic and chloroplastic fructose-1,6
      bisphosphatase (FbPase) is an extra peptide in the middle of chloroplast FbPase
      which contains three additional cysteine residues. Sit-directed mutagenesis
      experiments have shown that at least two of these cysteine residues are involved
      in forming the regulatory disulfide bridge [Jacquot, J.-P. et al., FEBS Lett. 401
      (1997) 143-147] which is the presupposition for the thioredoxin-dependent control
      of chloroplast FbPase activity. Here we report that each subunit of the FbPase
      contains an additional structural disulfide bridge which has been observed by
      combined application of thioredoxins and sulfitolysis. Observation of the
      structural disulfide bridges by sulfitolysis was only possible when the FbPase
      was already specifically reduced by the homologous thioredoxin species TRm. and
      TRf from spinach chloroplasts. Interestingly, the accessibility of the structural
      disulfide bridge for sulfite ions depends on the thioredoxin species engaged in
      the thioredoxin/FbPase complex.

PMID- 9537526
TI  - Involvement of protein-tyrosine phosphorylation and dephosphorylation in sperm
      induced Xenopus egg activation.
AB  - We have analyzed tyrosine-phosphorylated proteins in Xenopus laevis eggs before
      and after fertilization by immunoblotting with anti-phosphotyrosine antibody. A
      number of egg proteins with different subcellular distribution became tyrosine
      phosphorylated or dephosphorylated within 30 min after insemination. Tyrosine
      kinase-specific inhibitors genistein and herbimycin A were found to inhibit sperm
      induced egg activation judged by the egg cortical contraction. Surprisingly,
      sodium orthovanadate, a tyrosine phosphatase inhibitor, also inhibited the egg
      activation. Moreover, we found that fertilization-dependent tyrosine
      dephosphorylation of 42-kDa mitogen-activated protein kinase was inhibited in
      genistein-treated eggs. These results suggest that both protein-tyrosine
      phosphorylation and dephosphorylation pathways play an important role in the
      sperm-induced Xenopus egg activation.

PMID- 9537528
TI  - Growth curve of ruptured aortic aneurysm.
AB  - OBJECTIVE: We hypothesized that the aortic aneurysm might grow biexponentially.
      The object of this study was to determine the biexponential growth curve of
      aortic aneurysm. DESIGN: A fifteen-year retrospective review of CT images of
      aortic aneurysm. SETTING: Major cardiovascular referral center. PATIENTS:
      Patients with true aortic aneurysm who were followed up with CT and performed CT
      at their aneurysmal ruptures. MEASURES: The largest short-axial diameters of the
      outer contour of the aneurysms were measured. Aortic aneurysmal diameters were
      normalized by those at ruptures, and the plots were fitted to the biexponential
      curve. RESULTS: Eight patients out of 1481 had been followed up with CT scans. In
      regression analysis, the values fit well to the biexponential equation: d(t) =
      0.8345 exp (0.0052 t) + 0.1653 exp (0.8275 t), r = 0.934 where d(t) is the
      normalized diameter, and t is months before rupture. The first part of the
      equation mainly expresses the slow growth, and the second expresses the rapid
      growth shortly before rupture. CONCLUSIONS: Aortic aneurysm began to grow faster
      at about three months before rupture. It is important to find out the point that
      the growth of aortic aneurysm changes its rate faster than before, and once the
      point is observed, elective repair should be considered.

PMID- 9537527
TI  - The activity of c-myb antisense oligonucleotide to prevent intimal hyperplasia is
      nonspecific.
AB  - BACKGROUND: We sought to determine the efficacy and specificity of a new c-myb
      antisense by inhibiting neointimal hyperplasia in a rat abdominal aorta injury
      model. Using c-myb antisense oligonucleotides, inhibition of vascular smooth
      muscle cell proliferation has been reported. METHODS: Sixty-six male Wistar rats
      had a de-endothelialization of the abdominal aorta. Following a double blind
      randomization protocol, F127 pluronic gel containing one of the five
      oligonucleotides or plain gel was applied around the aorta: 1) 18-mer c-myb
      antisense (AS18) with four contiguous guanosines (G-quartet); 2) 15-mer c-myb
      antisense (AS15) without G-quartet; 3) 1-bp mismatch AS15 without G-quartet
      (MM1); 4) an oligonucleotide with G-quartet (4G), whereas the other bases were
      chosen at random; 5) 1-bp mismatch 4G without G-quartet (MM2). After 21 days all
      rats were sacrificed and aortas harvested for histomorphometric evaluation. Four
      rats were given fluorescent-labeled oligonucleotides to study in vivo
      localization after local advential delivery. RESULTS: Morphometric analysis
      showed significant suppression of neointimal hyperplasia in AS18 and 4G and MM2
      groups compared with GEL, AS15 and MM1 groups (p<0.05). The oligonucleotide
      labeled aortas showed penetration of the oligonucleotides into the media which
      increased with time. CONCLUSIONS: Our findings pointed to the potential non
      specificity of the c-myb antisense oligonucleotide in vivo. Such results will
      minimize the importance of antisense strategy as a potential therapeutic for
      preventing neointimal hyperplasia. The two oligonucleotides with a G-quartet
      inhibited neointimal hyperplasia in our model. Exploring a non-antisense
      mechanism, G-quartet oligonucleotides as potential drugs to reduce neointimal
      hyperplasia is attractive.

PMID- 9537529
TI  - Long term results after rotation angioplasty and catheter atherectomy. A
      retrospective analysis.
AB  - Rotationangioplasty and catheter atherectomy using the TEC device was performed
      in 33 patients with peripheral arterial occlusive disease. Thirty-five femoral or
      popliteal artery occlusions could be recanalized with an initial patency of 100%.
      After 5 years the patients were re-evaluated by clinical examination, colour
      duplex scanning and in 5 cases by intra-arterial angiography. According to life
      table analysis there was no patent femoral or popliteal vessel after 5 years in
      those patients treated initially for rest pain or ischemic tissue loss. 82% of
      those treated for claudication had a re-occluded artery. In 5 cases a major
      amputation was necessary. 42% of those patients who were initially treated far
      disabling claudication had a severe deterioration of their functional status with
      development of critical ischemia. In 9 of these cases reconstructive arterial
      surgery was required which failed in one patient with subsequent limb loss. In
      the retrospective study presented patients with occlusions up to 30 cm and more
      were treated. Combining two interventional techniques there is a high initial
      success rate with poor long term results. Therefore these devices should be
      reserved for high risk patients who would not tolerate reconstructive vascular
      surgery. They should not be used in patients with claudication although even
      extensive occlusions can be recanalized there is an imminent danger of causing
      significant deterioration of the patients functional status.

PMID- 9537530
TI  - Tibioperoneal bypass for popliteal arterial occlusion.
AB  - OBJECTIVE: To clarify the clinical features of chronic arterial occlusive disease
      in which the main lesion occurs in the popliteal artery (OPA). EXPERIMENTAL
      DESIGN: This was a retrospective study with a follow-up of 1 to 163 months.
      SETTING: A department of surgery in a university hospital. PATIENTS: Fifty-six
      patient who underwent tibioperoneal bypasses: 31 patients with OPA, and 25 with
      an extensive occlusive lesion from the femoral to popliteal artery (OFPA).
      INTERVENTION: All bypasses were performed using reversed saphenous veins under
      tourniquet ischemia. MEASUREMENTS: The background of the patients and the
      surgical results, including long-term patency and postoperative arteriographic
      findings. RESULTS: Buerger's disease occurred most commonly in the OPA group
      (49%) and arteriosclerosis obliterans occurred most commonly in the OFPA group
      (64%). The 3-year primary and secondary cumulative patency rates of the grafts
      for OPA were 72% and 85% respectively, and were comparable with those of OFPA.
      Arteriographic analyses carried out in the follow-up period revealed no occlusive
      progression in the inflow artery. CONCLUSIONS: Popliteal-distal bypass is a
      reliable procedure in selected patients with OPA.

PMID- 9537531
TI  - Spontaneous retrograde dissection of the entire thoracic aorta originating in the
      abdominal aorta. Case report and review of the literature.
AB  - Spontaneous retrograde thoracic extension of the abdominal aortic dissection is
      extremely rare and difficult to manage. Only five cases have been previously
      reported in the English literature (dissection reaching the ascending aorta in
      four, dissection limited in the descending thoracic aorta in one), and all the
      cases of dissection which reached the ascending aorta were lethal. We herein
      report one case of a 37-year-old man who was operated on for spontaneous
      retrograde dissection of the entire thoracic aorta originating in the suprarenal
      abdominal aorta. Preoperative aortogram revealed the site of the intimal tear
      just above the celiac artery. He urgently underwent graft replacement of the
      descending thoracic aorta and the abdominal aorta with reimplantation of the
      thoracoabdominal visceral arteries. Although the patient had to undergo the
      second operation for the dissection of the remaining thoracic aorta four months
      postoperatively, he has been doing well 18 months after the second operation.

PMID- 9537532
TI  - Symptomatic abdominal aortic aneurysm and "situs viscerum inversus." Diagnostic
      and therapeutic approach.
AB  - BACKGROUND: We report one case of symptomatic aneurysm of infrarenal abdominal
      aorta in a patient symptomatic for acute abdomen. METHODS: The patient was
      accepted at the Emergency Care Unit and the routine admission tests were taken.
      US of the abdomen revealed a <<Situs Viscerum Inversus Totalis>> (SVI)
      disposition of the organs and an aneurysm of the abdominal aorta below the renal
      arteries. Patient underwent an aorto-aortic straight graft CONCLUSIONS: In this
      case-report we show SVI cannot be considered a problem in the surgical treatment
      of symptomatic abdominal aortic aneurysms.

PMID- 9537533
TI  - Embolization of a false aneurysm fistulized to the contralateral common iliac
      artery. A case report.
AB  - We describe a patient who developed a false aneurysm interposed between bilateral
      common iliac arterial stumps 6 years after replacement of a bifurcated graft for
      repair of abdominal aortic aneurysm. The false aneurysm formed a fistula to the
      contralateral common iliac artery stump. In the light of this patient's history
      of severe arterial disease, weakness of the arterial wall was thought to be
      responsible for this anastomotic false aneurysm. Due to significant risk factors,
      the patient was treated with transcatheter intervention and he recovered without
      complications.

PMID- 9537534
TI  - Intrathoracic atherosclerotic aneurysm of the right subclavian artery. A case
      report.
AB  - The intrathoracic subclavian artery is a rare location for a peripheral arterial
      atherosclerotic aneurysm when compared with the femoral and popliteal arteries.
      Resection of the aneurysm and replacement with a prosthetic graft has come to be
      the most commonly performed procedure for this problem. Because of the tight
      adherence of surrounding tissues such as the vagal nerve, phrenic nerve, jugular
      veins, and their branches, we preferred an exclusion method with
      revascularization to the aneurysmorrhaphy and achieved a good result. We report
      the clinical aspects of such a case.

PMID- 9537535
TI  - Elective or emergent interventional radiology through introducer sheath inserted
      during emergent vascular surgery for critical ischemia.
AB  - During performance of embolectomy or thrombectomy one often encounters arterial
      stenoses. These may be treated by adjunctive intraoperative angioplasty during
      the operation or delayed percutaneous angioplasty (PTA) may be performed in the
      interventional radiology department. Delayed PTA may have to wait until the wound
      has healed, and during this time there is a risk of re-occlusion. It may often be
      desirable to perform the radiologic intervention at a later time than the thrombo
      embolectomy for logistic reasons. The vascular surgeon and interventional
      radiologist may perform best when working in the environment that they are
      accustomed to. Also, measurement of vascular diameters, and selection of proper
      balloon and stent sizes can usually be performed most accurately with the
      equipment that is available in the X-ray department. We treated selected patients
      who underwent thromboembolectomy or thrombendarterectomy in the groin for
      critical ischemia, and who also had clinically important proximal or distal
      stenoses, in the following way: an arterial sheath was inserted through the wound
      and the patients were transferred to the interventional radiology laboratory
      where they underwent PTA. A continuous over and over suture with 3 bites of a 6-0
      polypropylene suture in the arteriotomy for the sheath appeared to be the best
      way to secure hemostasis. The wound was closed around this suture and the
      arterial sheath. After removal of the sheath slight traction was applied to the
      polypropylene suture and maintained for 1-2 days by application of a hemostat at
      skin level. The technique is illustrated with a case report.

PMID- 9537537
TI  - Long-term survival benefit of internal thoracic artery grafting is negligible in
      a patient with bad ventricle.
AB  - BACKGROUND: Although the internal thoracic artery (ITA) graft is well known for
      its benefit of enhancing patient longevity after coronary artery bypass grafting
      (CABG), whether its superior patency is associated with improved patient survival
      at all levels of left ventricular function is unknown. The purpose of this study
      was to determine whether the use of ITA grafting during CABG confers improved
      survival benefit to patients with impaired preoperative left ventricular
      function. METHODS: A retrospective chart review was performed in 966 patients who
      had undergone isolated primary CABG between 1984 and 1995. The study population
      included 320 patients with only venous conduits (no-ITA group) and 646 patients
      with at least one ITA conduit (ITA group). A Cox partial likelihood approach was
      used to model the instantaneous mortality risk ratios as functions of ITA use and
      preoperative ejection fraction (EF). The forward stepwise regression model
      specifically examined the following potential confounders in the risk analyses:
      year of operation, patient age, weight, body surface area, graft location, number
      of grafts, perfusion time, ischemia time and Veterans Administration preoperative
      cardiac surgical risk estimates. RESULTS: Early (30-day) mortality in the ITA
      group (0.5%) was lower than the no-ITA group (4.1%) (p=0.0004). While 91% of the
      ITA group patients were still alive, only 70% of the no-ITA group patients were
      long-term survivors (p=0.0001). The ITA risk ratios for the increasing
      proportions of EF were not the same. In patients with E<0.40, the ITA risk ratio,
      2.96, was significantly different (p=0.0001). It was only for EF >0.46, a
      significant survival benefit due to an ITA graft could be detected. The ITA-EF
      relationship was not confounded by the inclusion of those potential confounding
      variables in the model. CONCLUSIONS: Patient survival after CABG using an ITA
      graft may be affected by the level of preoperative EF. The internal thoracic
      artery-specific patient survival benefit appears to be less in a patient with
      poor left ventricular function.

PMID- 9537536
TI  - The effects of the hypothermic management of brain dead dogs on preserving graft
      viability in heart transplantation.
AB  - The effect of hypothermic management for brain dead dogs on preserving graft
      viability was evaluated through preservation and transplantation. After the
      occurrence of brain death, 43 dogs were divided into two groups; the normothermic
      group (37.2+/-0.3 degrees C) and the hypothermic group (31.8+/-0.3 degrees C)
      according to the esophageal temperature. After the 6-hour management of brain
      dead donors, the heart beat was arrested using a cardioplegic solution followed
      by coronary vascular bed washout. The donor heart was then harvested and
      preserved for 12 hours with simple immersion into the University of Wisconsin
      solution. Following preservation, orthotopic transplantation was performed in six
      grafts randomly selected from each group. During the 6-hour management of brain
      dead dogs; 1) heart rates, rate-pressure products, and the total amount of
      catecholamine were significantly (p<0.05) lower in the hypothermic group than in
      the normothermic group, and 2) lactate contents collected from the coronary sinus
      blood and O2-extraction rates of the heart tended to be lower in the hypothermic
      group than in the normothermic group. During 12 hours of preservation,
      intracellular pH and creatine phosphate contents were higher in the hypothermic
      group than in the normothermic group. Following orthotopic transplantation, the
      animals in the hypothermic group showed a significantly (p<0.05) higher recovery
      rate of left ventricular (LV) pressure and the maximum rate of the rise of LV
      pressure compared with normothermic group animals. We conclude that the
      hypothermic management of brain dead dogs may be effective in preserving graft
      viability and may provide a clinical application for heart transplantation with
      acceptable outcomes.

PMID- 9537538
TI  - Surgical treatment of Marfan patients with aneurysms and dissection of the
      proximal aorta.
AB  - BACKGROUND: The authors retrospectively analyzed early and late results of
      surgical treatment for 79 Marfan patients with aneurysms and dissection of the
      proximal aorta. METHODS: From September 1979 to February 1996, 79 patients with
      Marfan syndrome underwent aortic root replacement using composite grafts (n=68,
      Bentall-technique 63, button-technique 5), and ascending aortic replacement with
      a valve-sparing procedure (n=11). There were 12 patients (15.2%) who
      simultaneously received partial or total arch replacement. 55 patients (69.6%)
      were male, and 24 female (30.4%). The average age was 33.8 years. Forty-one
      patient (51.9%) had non-dissecting aneurysms while the remaining 38 patients
      suffered from either acute (24.0%) or chronic aortic dissection (24.0%). The
      aortic valve was involved in 97.5% of all cases. RESULTS: The total early
      mortality (< or =30 days) was 3.8%, 10.5% for acute aortic dissection and 2.4%
      for non-dissecting aneurysms. There were no early postoperative deaths in
      patients after valve-sparing operation and in those with chronic aortic
      dissection. The follow-up rate was 98.7%. During a mean follow-up of 68+/-25
      months 10 patients (13.3%) died and cardiac complications were a common cause of
      the late deaths. There was no late mortality in the valve-sparing operations
      during a mean follow-up period of 8+/-6 months, however, 1 required valve
      replacement. 19 (25.3%) of the 75 patients surviving late have undergone 25
      secondary operations on the cardiovascular system. Reoperations at aortic sites
      distant from the original were much more frequent after primary repair for acute
      and chronic dissection when compared to non-dissecting aneurysms (p<0.005).
      Actuarial survival rate of all patients with composite graft replacement
      including early deaths was 91.2% at 1 year, 84.4% at 5 years and 75.2% at 10
      years. CONCLUSIONS: Composite graft insertion has become the gold standard for
      treating Marfan-patients with non-dissecting and dissecting aneurysms of the
      aortic root. Our early experience in 11 patients with valve-sparing procedures
      indicated that this,variant may be the better choice in selected patients.

PMID- 9537539
TI  - The assessment of internal mammary artery grafts by colour Doppler in coronary
      artery surgery.
AB  - BACKGROUND: Various studies in progress on the flow and diameter parameters based
      assessment and suitability of internal mammary artery by preoperative colour
      Doppler examination in coronary artery surgery. Postoperative visualisation of
      these grafts is also in evolution. Due to its noninvasive approach, colour
      Doppler sonography is taking its place in the follow-up of coronary artery bypass
      procedure. The aim of this study was to show the effectiveness and feasibility of
      colour Doppler in the routine postoperative follow-up evaluation. METHODS: In
      GATA Haydarpasa Education Hospital, coronary artery bypass grafting was performed
      by anastomosing left internal mammary artery to left anterior descending artery
      and saphenous veins to remaining lesions of the coronary arteries in 36 male
      patients between the ages of 42 to 66 (mean 54.8) in 1995. Left internal mammary
      artery and unused right internal mammary artery were imaged by colour Doppler six
      to eight weeks after the operations in all cases. Coronary angiography was also
      performed in two cases 4 months postoperatively. RESULTS: Colour Doppler
      sonography findings showed that the diameter of left internal mammary artery was
      larger (p=0.03) and mean flow value was greater than intact right internal
      mammary artery (p=0.02). CONCLUSIONS: These results shows that colour Doppler
      sonography should be applied as a noninvasive method, in the follow-up of
      internal mammary artery grafts after coronary artery revascularisation.

PMID- 9537540
TI  - Inhaled nitric oxide in infants and children after open heart surgery.
AB  - OBJECTIVE: To assess the effects of inhaled nitric oxide (NO) on oxygenation and
      pulmonary circulation in infants and children with critical pulmonary perfusion
      and/or hypoxemia after open heart surgery. STUDY: A prospective case series
      report. SETTING: A multidisciplinary pediatric intensive care unit in a
      University hospital PATIENTS: From June 1993 to March 1996 37 pediatric patients
      after open heart surgery were treated with inhaled NO. Their mean age was 2.9+/
      0.6 years, their mean body weight 12.6+/-1.8 kg. METHODS: Inhaled NO was applied
      using a microprocessor controlled delivery system which continuously measured NO
      and NO2 by the chemilumniscence method. Monitoring included ECG, continuous pulse
      oximetry (SaO2), arterial (AP), central venous (CVP) and left atrial (LAP)
      pressures and in 8 patients a pulmonary artery (PAP) pressure. Inhaled NO was
      started at an SaO2 <90% with a fraction of inspired oxygen concentration (FiO2)
      >0.7, at a mean pulmonary artery pressure (MPAP) >50% of the mean arterial
      pressure (MAP), and in patients after Fontan-procedure at a CVP-LAP pressure
      gradient >10 mmHg. RESULTS: The mean dose of inhaled NO was 3.7+/-0.3 ppm and the
      mean duration was 112+/-14.7 hours. For the whole group SaO2 increased from
      79.6+/-2.3 to 90.1+/-1.5% (p<0.01) within 20 minutes of NO-inhalation. Inhaled NO
      significantly decreased the MPAP from 47.8+/-4 to 27.5+/-2.3 mmHg (p<0.01) in 8
      patients with postoperative pulmonary hypertension and significantly decreased
      the transpulmonary pressure (CVP-LAP) from 14.3+/-0.8 to 7.3+/-0.9 mmHg (p<0.01)
      in 16 patients after Glenn- or Fontan-procedure. CONCLUSIONS: Inhaled NO is very
      effective to decrease pulmonary artery pressure, to improve oxygenation, and to
      improve Fontan-circulation in infants and children after open heart surgery.

PMID- 9537541
TI  - The significance of oncometry for infusion therapy during pediatric heart
      surgery.
AB  - BACKGROUND: The colloid osmotic pressure (COP) is not routinely assessed during
      pediatric heart surgery. Two cases of unrecognized hyperoncotic states associated
      with renal failure have been observed after pediatric heart surgery. We studied
      the hypothesis that the COP cannot be estimated from the total plasma protein
      (TPP) or albumin level. METHODS: The course of COP and its correlation to the TPP
      and albumin level were investigated in 25 children undergoing elective heart
      surgery. Infusion therapy was performed solely on the basis of clinical
      parameters and TPP/albumin levels. COP values were determined in a blinded
      fashion at the end of the study. RESULTS: No correlation between TPP/albumin and
      the COP could be determined preoperatively. On arrival at the ICU correlation was
      strong. A weak correlation was observed at 24 hours and 48 hours after surgery.
      However, the observed wide range of the confidential bands indicates that the COP
      cannot be estimated correctly, neither from the TPP, nor from the albumin level.
      Due to colloidal oversubstitution COP was significantly increased compared to
      preoperative level at 48 hrs following surgery. CONCLUSIONS: As estimation of COP
      from TPP or albumin level is inaccurate, oncometry should be performed during
      pediatric heart surgery.

PMID- 9537542
TI  - Management of postoperative fever in cardiovascular surgery.
AB  - BACKGROUND: The causes and management of postoperative fever were studied.
      MATERIALS AND METHODS: During a four-year-period beginning in January of 1991,
      high fever over 38.5 degrees C max occurred in twenty-five (6%) out of 395
      patients who underwent cardiovascular surgery. RESULTS: Nine of the patients
      (28%) evidenced bacteriological infections as follows; 3 cases of mediastinitis,
      2 cases of respiratory tract infection, 1 case of MRSA colitis and a wound
      infection in one case. The three patients with mediastinitis died and the two
      cases of MRSA were detected from the culture of pacemaker leads. Bacteriological
      infection was not detected in other 18 (72%) patients with fever. However, we
      speculated that the clinical causes of fever in 9 out of 18 patients were as
      follows; catheter fever in 3 patients, acalculous cholecystitis in 2, fungus
      infection in 2, aseptic meningitis in one and viral myelitis in one patient. Two
      patients with acalculous cholecystitis recovered after percutaneous transhepatic
      gallbladder drainage. The causes of fever were not apparent in nine patients,
      however the source might be related to artificial prostheses used
      intraoperatively in five patients. C-reactive protein (CRP) was elevated beyond
      10 mg/dl in 13 (52%) of the 25 patients. CRP increased in all seven
      bacteriologically positive patients and in six (32%) of the bacteriologically
      negative patients. CONCLUSIONS: Precise and prompt bacterial examinations are
      necessary in patients with CRP elevation because the origins of fever were
      bacteriological in only 28% of the patients with a high fever. Good prognoses may
      be obtained by suitable management in bacteriologically negative patients.

PMID- 9537544
TI  - Open chest myocardial biopsy: a simple and safe method.
AB  - The authors describe a simple method to perform left ventricular biopsies during
      open heart surgery. An automatic gun shaped device is used by one hand of the
      surgeon: the sample is obtained in a few seconds, at any time of the surgical
      procedure. It consists of a transmural piece of tissue, averaging 18 mm3 in
      quantity. The device has been used in 20 patients who underwent coronary artery
      revascularization. All the biopsies were successful. No complications occurred.

PMID- 9537543
TI  - The Sorin Bicarbon valve: clinical evaluation in Israel.
AB  - BACKGROUND: Four collaborating centers pooled their results with the Sorin
      Bicarbon Bileaflet valve. MATERIAL AND METHODS: Between 6/91 and 11/95, 431
      patients, 235 males and 196 females, underwent valve replacement using the new
      Sorin prosthesis; age range: 16-88, mean 61.4 yrs. OPERATIONS: AVR - 206, MVR -
      177, TVR - 1, DVR - 47. Additional procedures - 139: CAB -117, valve repair - 22.
      AV sizes: 19-27, MV sizes: 21-33. RESULTS: Thirty day mortality was 4.3%. Early
      complications included: CVA - 1.4%, +ve blood culture - 2%, reop for bleeding -
      5%. Late complications: infective endocarditis - 2.3%, valve thrombosis - 0.2%,
      thromboemboli - 2.5%, major bleeding - 1.6%, reoperation - 3%, late deaths (all
      causes) - 4.3%. No structural deterioration has been reported with this valve and
      acceptable gradients have been observed. Hemolysis is negligible. CONCLUSIONS:
      Based on this intermediate experience the Sorin Bicarbon prosthesis is well
      designed with good hemodynamic properties, and an acceptably low incidence of
      complications.

PMID- 9537545
TI  - Spontaneous pneumothorax: determinants of surgical intervention.
AB  - OBJECTIVE: To assess the long term efficacy of intercostal tube drainage for
      spontaneous pneumothorax and determine the clinical parameters associated with
      surgery. EXPERIMENTAL DESIGN: Retrospective analysis with a mean follow-up of
      62.3+/-19.3 months (range 23 to 94 months). SETTING: Riyadh Medical Complex,
      Riyadh (Saudi Arabia), the biggest referral centres for Ministry of Health
      providing specialized hospital care. PATIENTS: Over a period of six year, 123
      patients had 182 episodes of spontaneous pneumothorax. Male to female ratio was
      29.75:1 (p=0.00001). Average age was 26.35+/-8.33 years for men and 37.25+/-14.6
      years for women (p=0.01). Seventy eight per cent of patients were aged 11 to 30
      years (p=0.00001). Majority were nonsmokers (100/123, p=0.00001). It was first
      episode of spontaneous pneumothorax for 86 patients. Other 37 patients had 57
      episodes previously (mean 1.54+/-0.73; range 1 to 4). INTERVENTIONS: Intercostal
      tube drainage for all patient with spontaneous pneumothorax. Limited axillary
      thoracotomy with bullectomy and pleuroabrasion for 32 patients not responding to
      intercostal tube drainage. RESULTS: Intercostal tube drainage alone had success
      rate of 90.7% in first, 52.4% in second, 15.4% in third and 0% for more than 3
      episodes of spontaneous pneumothorax. Among the 32 patients who underwent
      surgery, only one had early recurrence that did not require drainage. We found
      that patients with history of recurrence, respiratory distress and those
      requiring tube thoracostomy for more than 4 days and negative suction to expand
      the lung were more liable to undergo surgical intervention (p=0.00001 for all
      variables). CONCLUSIONS: We recommend early surgery to hasten recovery and
      shorten the hospital stay in patients with history of recurrent spontaneous
      pneumothorax, respiratory distress and those requiring tube thoracostomy for more
      than 4 days and negative suction to expand the lung.

PMID- 9537546
TI  - Empyema in children.
AB  - Empyemas develop following bacterial pneumonias, thoracic trauma and surgery
      which are still among the common diseases, causing illness and death throughout
      the developing world. With the advent of potent antibiotics the mortality of
      empyema has been drastically reduced. In this study 52 patients (29 boys and 23
      girls) with thoracic empyema were evaluated retrospectively. In this series the
      causes of empyema were postpneumonic in 50 patients, esophageal anastomotic leak
      in one patient, and thoracic trauma in one patient. The diagnosis was suspected
      clinically and by the finding of a pleural effusion on chest roentgenogram.
      Definitive diagnosis was confirmed by pleural aspiration which pus was obtained.
      Responsible organisms included; Staphylococcus aureus, Streptococcus pneumonia,
      Haemophilus influenza, pseudomonas, and Klebsiella. The most common is
      Staphylococcus aureus. The patients were treated in various ways; 14 patients
      were treated with antibiotics and thoracentesis, 38 patients were treated with a
      closed tube thoracostomy. Eight of 38 patients had the chest tube converted to an
      open empyema tubes for long term management. Fourteen of 38 patients developed
      abcess formation. Nine of 14 patients were treated with computed tomography
      guided catheter placement, five patients encountered thoracotomy and
      decortication. In this article, appropriate treatment and result of long-term
      follow-up of empyema were evaluated.

PMID- 9537547
TI  - Evaluation of complex mediastinal masses by magnetic resonance imaging.
AB  - MRI was used to diagnose a mediastinal mass in a elderly patient with previous
      repair of aortic coarctation. MRI excluded aneurysm by demonstrating a
      homogeneous mass encasing aorta and the bypass graft. A second thoracotomy was
      avoided. Moreover, outpatient testing was performed, without exposure to contrast
      agents, ionizing radiation, or an invasive procedure.

PMID- 9537548
TI  - Carcinosarcoma of the lung. Report of three cases.
AB  - This article presents three cases of carcinosarcoma of the lung which is
      considered to be a rare neoplasm. The authors describe supposed etiology,
      clinical symptoms, preoperative diagnostic difficulties, surgical interventions
      performed, postoperative course and follow-up. The role of modern
      histopathological techniques like use of monoclonal antibodies reaction against
      keratin, vimentin and neurofilaments in differential diagnosis is emphasized.
      Short review of other authors reports is presented.

PMID- 9537549
TI  - Ventriculo-peritoneal shunts in children reveal the natural history of closure of
      the processus vaginalis.
AB  - PURPOSE: Little information is known about the natural history of closure of the
      processus vaginalis. The authors studied children who had ventriculoperitoneal
      shunts to determine the natural history of closure of the processus vaginalis and
      to better understand the role of intraabdominal pressure in the etiology of
      congenital inguinal hernia. MATERIALS AND METHODS: A retrospective review of all
      children undergoing insertion of ventriculoperitoneal shunts between 1985 and
      1995 at the Royal Children's Hospital was undertaken. In each case, the sex, the
      cause of hydrocephalus, the age at insertion of the shunt, and the subsequent
      development of an inguinal hernia or hydrocele was recorded. RESULTS: There were
      430 children in the study. An inguinal hernia developed in 15% of children after
      insertion of a ventriculoperitoneal shunt, and a hydrocele developed in an
      additional 6% of boys. Inguinal hernias were bilateral in 47% of boys and 27% of
      girls. The incidence of subsequent development of an inguinal hernia or hydrocele
      was closely related to the age of insertion of the ventriculoperitoneal shunt,
      being 30% during the last 8 weeks of gestation and the first few months of life,
      then falling quite sharply to reach about 10% at 1 year. CONCLUSIONS: The high
      occurrence of inguinal hernias and hydroceles after ventriculoperitoneal shunt
      insertion supports the role of raised intraabdominal pressure in the etiology of
      these conditions. It appears that raised intraabdominal pressure is associated
      with an increased incidence of clinical hernias, but not with increased incidence
      of patency of the processus vaginalis. The development of an inguinal hernia or
      hydrocele after insertion of a ventriculoperitoneal shunt can be used as an
      indirect marker of patency of the processus vaginalis at the time of insertion of
      the shunt. From this, we propose that the processus vaginalis remains patent in
      at least 30% of children in the first few months of life, after which time the
      patency rate appears to fall off quite sharply.

PMID- 9537550
TI  - Pyogenic liver abscess in children--South Indian experiences.
AB  - PURPOSE: Eighteen cases of pyogenic liver abscess (PLA) admitted at JIPMER
      hospital, South India, over a 6-year period were analyzed to document the
      clinical profile and to evaluate the management of PLA among children. METHODS:
      Records of all these patients were reviewed for presenting signs and symptoms,
      any associated condition, investigative results, management, and follow-up
      findings. RESULTS: The overall incidence of PLA was 78.9 per 100,000 pediatric
      (under 12 years) admissions. One patient had aplastic anemia and was on long-term
      steroid therapy, whereas another had measles in recent past. Moderate to severe
      malnutrition was present in five (27.8%) and ascariasis in seven (38.9%)
      children. Common presentations were fever (100%), abdominal pain (76.9%), and
      tender hepatomegaly (83.3%). Ultrasonography results were positive in all cases.
      Fourteen patients (77.8%) had solitary liver abscess, and four had multiple
      abscesses. Organism was isolated in 11 cases (63.6%), and Staphylococcus aureus
      was the commonest isolate (66.7%). All patients received antibiotics. Twelve
      cases were managed conservatively with antibiotics alone, of these only two
      (16.7%) required drainage later on. Percutaneous aspiration was also undertaken
      in four additional (22.2%) cases and open drainage in two (11.1%), at
      presentation. The overall mortality rate was 11.1%. Time taken for complete
      resolution ranged from 10 days to 40 days. CONCLUSIONS: Any child presenting with
      fever, abdominal pain, and tender hepatomegaly should be subjected to ultrasound
      scan for early detection of PLA. S aureus is the commonest causative agent.
      Enterobacteriaceae contribute significantly during infancy. A combination of
      cloxacillin and gentamicin or a third generation cephalosporine and gentamicin,
      especially in infants, is a satisfactory initial coverage. Therapeutic drainage
      is not a must in all cases of PLA. When required, percutaneous needle aspiration
      is safe and effective. Resolution and significant reduction in mortality has been
      made possible by early detection and optimum antibiotics therapy.

PMID- 9537551
TI  - High oxygen delivery and extraction by perfluorocarbon-primed extracorporeal
      membrane oxygenation do not prevent anaerobic metabolism in rabbits.
AB  - PURPOSE: This study was designed to evaluate the advantage of perfluorocarbon
      (PFC) emulsion priming for venoarterial extracorporeal membrane oxygenation
      (ECMO) by comparison with hydroxyethyl starch (HES) solution in rabbits (2.8 to
      3.9 kg). RESULTS: ECMO initiation was accompanied by a profound decrease in
      hematocrit (from 40.1% to 14.9%) in both groups. The arterial and the right
      atrial oxygen contents in the PFC group (n = 4; 38.5 and 11.5 mL/dL) were greater
      than in the HES group (n = 5; 7.0 and 5.1 mL/dL). Right atrial oxygen tension in
      the PFC group increased at the beginning of ECMO (from 38.4 to 51.2 mm Hg; P =
      .031) and remained higher than in the HES group for 60 minutes. These results
      indicate that oxygen supply and extraction in the PFC group were much greater
      than in the HES group. However, plasma lactate increased progressively during the
      120-minute ECMO procedure in both groups (from 1.8 to 14.5 in the HES group, and
      from 2.3 to 12.2 in the PFC group). CONCLUSION: Perfluorocarbon priming for ECMO,
      although providing high oxygen delivery and extraction, does not prevent
      anaerobic metabolism.

PMID- 9537552
TI  - Successful surgical outcome in children with sickle hemoglobinopathies: the Duke
      University experience.
AB  - BACKGROUND/PURPOSE: Surgery in patients with sickle hemoglobinopathies can be
      problematic because of the potential for sickling events in the perioperative and
      postoperative period. The authors and others have previously reported successful
      surgical outcomes using an aggressive erythrocyte transfusion regimen, designed
      to alleviate anemia and to reduce the percentage of sickle hemoglobin to below
      30%. Recently, a randomized trial compared this aggressive regimen with a more
      conservative transfusion regimen and found no differences in perioperative
      complications. The incidence of complications, however, was very high in each
      group (31% to 35%). METHODS: The authors therefore analyzed retrospectively their
      surgical experience in children with sickle hemoglobinopathies over the past 10
      years to determine the efficacy of an aggressive transfusion regimen and skilled
      perioperative care in their patient population. RESULTS: A total of 130 surgical
      procedures were performed on 92 children including 54 cholecystectomies (42%), 23
      splenectomies (18%), 12 ENT procedures (9%), 11 central line placements and
      removals (8%), 7 herniorrhaphies (5%), 7 appendectomies (5%), and 16
      miscellaneous operations (13%). The mean age of the children was 10 years (range,
      1 to 22 years), and the mean weight was 32.1 kg (range, 9.9 to 76.8 kg). The
      average hemoglobin (mean +/- 1 SD) at the time of surgery was 11.2+/-1.3 g/dL,
      and the average percent hemoglobin S was 21+/-11%. CONCLUSIONS: Relatively few
      transfusions were required to achieve these endpoints, and the complications
      resulting from transfusions were minimal. Similarly, the number of perioperative
      and postoperative events was very low.

PMID- 9537553
TI  - Esophageal/pyloric ligation enhances development of the murine fetal stomach in
      organ culture.
AB  - PURPOSE: The authors hypothesized that increased intraluminal pressure in the
      fetal stomach would enhance development in a murine organ culture model. METHODS:
      Gestation day 14 (Gd14) fetal stomachs from time-dated pregnant CD-1 mice (term,
      20 days) were maintained in organ culture for 7 days. Some stomachs were ligated
      at the gastroesophageal (GE) and pyloroduodenal (PD) junctions. Others were left
      unligated. Gd14, Gd16, and Gd18 stomachs were taken as well to compare
      organogenesis in vivo. Tissues were processed for histological, morphometric, and
      immunohistochemical analysis, as well as total protein and DNA determination.
      RESULTS: The ligated stomachs were visibly distended compared with unligated
      stomachs in organ culture after 7 days. The length and width of the 7-day in
      vitro ligated stomachs were significantly increased compared with unligated
      (2.97+/-0.04 mm v 2.48+/-0.05 mm and 2.14+/-0.04 mm v 1.57+/-0.08 mm,
      respectively, P < .05). Mucosal epithelial cells showed nuclear polarization, and
      there was a distinct outer muscle layer in the ligated stomachs, but not in the
      unligated stomachs, which demonstrated pseudostratified epithelial cells in the
      mucosa. The ligated stomachs had increased in mucosal thickness compared with
      unligated (31.4+/-1.3 microm vs 24.9+/-0.9 microm, p < 0.05). The ligated
      stomachs also had significantly increased protein and DNA content when compared
      with unligated stomachs (65.8+/-3.1 microg and 23.3+/-1.2 microg v 55.0+/-2.7
      microg and 19.0+/-1.2 microg, respectively, P < .05). However, there were no
      significant differences noted between the protein to DNA ratios.
      Immunohistochemical staining for proliferating cell nuclear antigen (PCNA), a
      marker for cell proliferation, demonstrated increased proliferative activity of
      the mucosal epithelial cells in the ligated stomachs. CONCLUSIONS: Esophageal and
      pyloric ligation enhanced the development of the fetal stomach in vitro in
      comparison with unligated stomachs cultured under similar conditions.
      Developmental characteristics of the ligated stomachs paralleled that of Gd16
      stomachs in vivo.

PMID- 9537554
TI  - Arterio-venous extracorporeal membrane oxygenation of fetal goat incubated in
      artificial amniotic fluid (artificial placenta): influence on lung growth and
      maturation.
AB  - PURPOSE: The authors attempted to achieve extrauterine support of goat fetuses
      using arteriovenous extracorporeal membrane oxygenation (A-V ECMO) via umbilical
      vessels, incubated in a warm bath. They hypothesized that this extrauterine
      support system affected both the lung growth and maturation of goat fetuses.
      METHODS: Four goat fetuses at about 125 days' gestation (term, 150 days) were
      placed in this fetal ECMO system. Their four twin fetuses with similar body
      weights were harvested and examined for baseline data before ECMO (pre-ECMO
      data). The mean duration of A-V ECMO was 138.8+/-66.9 hours (range, 87 to 237
      hours). Tracheal ligation was performed on all four fetuses to prevent the efflux
      of fetal tracheal fluid and to collect a sample of tracheal fluid daily. The
      surfactant and electrolytes of the tracheal fluid were analyzed in pre-ECMO (twin
      fetuses) and during ECMO. The surfactant of lung tissue, and lung weight were
      analyzed in pre-ECMO (twin fetuses) and after ECMO. Plasma cortisol and T3 levels
      were also assayed as hormonal factors that affected lung maturation in pre-ECMO
      and during ECMO. RESULTS: The phospholipid, phosphatidylcholine, and lecithin
      sphingomyelin ratio of the tracheal fluid on day 5 during ECMO (15.0+/-7.1 mg/dL,
      53.4+/-26.5%, and 6.2+/-7.1) were elevated above pre-ECMO (10.0+/-4.6 mg/dL,
      43.0+/-0.6%, and 4.0+/-2.9), but there were no significant differences. The
      phosphatidylcholine and disaturated phosphatidylcholine of the lung tissue after
      ECMO were 72.3+/-15.4 mg/g and 19.2+/-8.2 mg/g, which were significantly higher
      than pre-ECMO (53.7+/-13.9 mg/g and 11.6+/-4.1 mg/g). The Cl- and K+ of the
      tracheal fluid were 123.5+/-6.2 mEq/L and 3.7+/-0.7 mEq/L on day 1 during ECMO,
      which were significantly lower than pre-ECMO (141.8+/-2.9 mEq/L and 6.8+/-1.1
      mEq/L), but they then recovered to pre-ECMO levels. The wet and dry lung weights
      after ECMO were 87.8+/-18.0 g and 6.3+/-1.9 g, which were significantly higher
      than pre-ECMO (49.3+/-5.9 g and 4.2+/-1.3 g). Plasma cortisol levels and T3
      levels during ECMO were significantly higher than pre-ECMO. Electron microscopy
      demonstrated a higher increase of mature type 11 cells in the lungs after ECMO
      than pre-ECMO. CONCLUSION: This fetal A-V ECMO system in the bath showed a
      production of surfactant, the maintenance of ion transport by the pulmonary
      epithelium, an increase in lung weight, and an increase in mature type II cells,
      resulting in lung growth and maturation.

PMID- 9537555
TI  - Partial dearterialization of the spleen in thalassemia major.
AB  - METHODS: Nine patients with thalassemia major (8 boys, 1 girl; age 3 to 8 years)
      who had signs of hypersplenism and required more than one blood transfusion per
      month (1 to 2 weeks) underwent partial dearterialization of the spleen (PDAS)
      from April through December 1992. All were on a low transfusion regimen (Hb < 10
      g%). Hematologic profile, IgM and splenic dimensions (SD) by sonography were
      determined preoperatively and postoperatively during follow-up periods. Isotopic
      scan was also performed a few months and 2 to 4 years after operation. The
      patients did not receive pneumovax or long-term prophylactic antibiotics. The
      procedure consists of division of the splenic arterial branches, except the one
      that supplies the superior pole, along with preservation of all the veins.
      RESULTS: Seven patients with SD less than 11 cm (6.9 to 10.8 cm; four with less
      than 9.5 cm) had uneventful recovery. Two others with SD greater than 13 cm (13.2
      to 13.5 cm) required total splenectomy a few days after PDAS because of splenic
      enlargement associated with high fever. One patient was lost to follow-up after
      18 months. The remaining six patients underwent follow-up for 4 to 4.5 years. The
      hematologic profile (Hb, RBC, platelet counts) showed significant improvement
      during follow-up period. The blood transfusion requirement in all patients was
      once every 25 to 32 days except one in which transfusion was increased to every 2
      to 3 weeks during the fourth postoperative year. The ultimate magnitude of the
      hematologic response compared with 15 matched splenectomized patients studied
      retrospectively in a 4-year period was almost the same in the majority after the
      first postsplenectomy year. There was no significant change in SD by sonography
      in four patients compared with preoperative state, but a 30% decrease was seen in
      the other two during the follow-up period. Isotope scan showed a functional
      residual spleen in all six, with no remarkable difference in size 4 years after
      operation, except in the one who relapsed. The IgM level did not fall
      significantly after operation, nor did signs of infection develop in any patient.
      CONCLUSION: PDAS is a safe and effective mode of therapy in thalassemia major,
      provided the disease is not advanced and SD does not exceed 11 cm in its greatest
      diameter.

PMID- 9537556
TI  - Etiology and retrieval of retained central venous catheter fragments within the
      heart and great vessels of infants and children.
AB  - BACKGROUND: The use of centrally positioned venous catheters plays an
      indispensable role in the care of infants and children. METHODS: Since 1992 the
      authors have seen nine patients who experienced fragmentation and migration of
      catheter fragments into the central circulation. The patients ranged in age from
      6 days to 15 years. RESULTS: Sites of migration included pulmonary artery (five
      patients), superior vena cava (two patients), hepatic vein and innominate vein
      (one patient). The elapsed time from recognition of retained catheter fragments
      until retrieval ranged from a few hours to 6 weeks. CONCLUSION: All retained
      fragments were successfully removed during cardiac catheterization without
      complications.

PMID- 9537557
TI  - Mechanism and prevention of port-site tumor recurrence after laparoscopy in a
      murine model.
AB  - BACKGROUND/PURPOSE: Although minimally invasive surgery (MIS) has been broadly
      applied in patients with cancer of the gastrointestinal tract, the etiology of
      port-site tumor recurrence (PSR) after laparoscopic cancer surgery remains
      unclear. The authors report here an analysis of PSR in a model of murine
      neuroblastoma after laparoscopic tumor biopsy and propose a mechanism for this
      complication as well as a potential treatment. METHODS: Immature 5- to 7-week old
      male A/J mice (18-23 g) were subcutaneously inoculated with the minimally
      immunogenic TBJ-neuroblastoma (TBJ-NB) in the left flank and divided into three
      treatment groups. The following operations were performed 14 days after tumor
      inoculation: group 1, additional intraperitoneal or intravenous injection of TBJ
      NB during CO2 pneumoperitoneum; group 2, simulated transperitoneal tumor biopsy
      using MIS techniques during either CO2 pneumoperitoneum or gasless suspension;
      Group 3, intraperitoneal (IP) or intravenous (IV) administration of
      cyclophosphamide on postoperative days 0 and 3 to prevent PSR after simulated
      tumor biopsy during CO2 pneumoperitoneum. RESULTS: In group 1, the incidence of
      PSR was 0% in the intravenously injected mice versus 63% in mice injected
      intraperitoneally with TBJ-NB. In group 2, no significant difference in the
      incidence of PSR was seen between simulated tumor biopsy (89%) animals with CO2
      pneumoperitoneum versus animals with gasless suspension (81%). In group 3, mice
      that did not receive any chemotherapy had an 89% incidence of PSR. Administration
      of cyclophosphamide via either the IP or IV route effectively prevented PSR,
      although there was no difference in the incidence of PSR between the two routes
      (IP 12% versus IV 13%). CONCLUSIONS: The data suggest that PSR in tumor-bearing
      hosts may be caused by direct seeding of exfoliated tumor cell, and not by
      hematogenous metastases. Contrary to the other reports, CO2 pneumoperitoneum was
      not found to be essential for the development of PSR. Furthermore, the authors
      conclude that postoperative chemotherapy may be useful in preventing PSR after
      MIS in patients bearing chemotherapy-sensitive tumors such as neuroblastoma.

PMID- 9537558
TI  - Operative treatment of truncal vascular injuries in children and adolescents.
AB  - BACKGROUND/PURPOSE: Pediatric truncal vascular injuries are rare, but the
      reported mortality rate is high (35% to 55%), and similar to that in adults (50%
      to 65%). This report examines the demographics, mechanisms of injury, associated
      trauma, and results of treatment of pediatric patients with noniatrogenic truncal
      vascular injuries. METHODS: A retrospective review (1986 to 1996) of a pediatric
      (< or = 17 years old) trauma registry database was undertaken. Truncal vascular
      injuries included thoracic, abdominal, and neck wounds. RESULTS: Fifty-four
      truncal vascular injuries (28 abdominal, 15 thoracic, and 11 neck injuries)
      occurred in 37 patients (mean age, 14+/-3 years; range, 5 to 17 years); injury
      mechanism was penetrating in 65%. Concomitant injuries occurred with 100% of
      abdominal vascular injuries and multiple vascular injuries occurred in 47%.
      Except for aortic and one SMA injury requiring interposition grafts, these wounds
      were repaired primarily or by lateral venorrhaphy. Nonvascular complications
      occurred more frequently in patients with abdominal injuries who were
      hemodynamically unstable (systolic blood pressure [BPS] <90) on presentation (19
      major complications in 11 patients versus one major complication in five
      patients). Thoracic injuries were primarily blunt rupture or penetrating injury
      to the thoracic aorta (nine patients). Thoracic aortic injuries were treated
      without bypass, using interposition grafts. In patients with thoracic aortic
      injuries, there were no instances of paraplegia related to spinal ischemia (clamp
      times, 24+/-4 min); paraplegia occurred in two patients with direct cord and
      aortic injuries. Concomitant injuries occurred with 83% of thoracic injuries and
      multiple vascular injuries occurred in 25%. All patients with thoracic vascular
      injuries presenting with BPS of less than 90 died (four patients), and all with
      BPS 90 or over survived (eight patients). There were 11 neck wounds in 9 patients
      requiring intervention, and 8 were penetrating. Overall survival was 81%;
      survival from abdominal vascular injuries was 94%, thoracic injuries 66%, and
      neck injuries 78%. CONCLUSIONS: Survival and subsequent complications are related
      primarily to hemodynamic status at the time of presentation, and not to body
      cavity or vessel injured. Primary anastomosis or repair is applicable to most
      nonaortic wounds. The mortality rate in pediatric abdominal vascular injuries may
      be lower than previously reported.

PMID- 9537559
TI  - Effects of anal invasive treatment and incontinence on mental health and
      psychosocial functioning of adolescents with Hirschsprung's disease and low
      anorectal anomalies.
AB  - BACKGROUND/PURPOSE: Recent studies of adolescents with Hirschsprung's disease
      (HD) and low anorectal anomalies (LARA) showed persistent impairment of fecal
      control in both groups, but very different mental and psychosocial outcome.
      METHODS: To explore possible reasons for these differences, 19 adolescents with
      HD (aged 10 to 20 years; median, 16) operated on by the Duhamel technique were
      compared with 17 adolescents with LARA (aged 12 to 20 years; median, 15). The 36
      adolescents were assessed for treatment procedures, bowel function, and mental
      and psychosocial outcome by data collected from medical records, physical
      examination, semistructured interview, and standardized questionnaires. The
      parents of 30 adolescents were also interviewed and completed questionnaires.
      RESULTS: Duration of anal invasive treatment procedure and current bowel function
      were associated with mental and psychosocial outcome. The treatment variable,
      duration of anal dilation, was the most significant predictor of the
      adolescents's mental health (R2 = .41, P < .01), whereas chronic family
      difficulties and parental warmth together with the current bowel function
      variables, fecal and flatus continence function, best explained the variance in
      psychosocial outcome (R2 = .77, P < .0001). Thus, the differences in treatment
      procedures and continence function between the HD and LARA groups may partially
      explain differences in mental and psychosocial outcome. CONCLUSIONS: These
      findings suggest that anal dilatation and continence dysfunction may have
      negative impact on mental health and psychosocial functioning. Indications for
      and ways of performing the procedure of dilation, and the treatment of persistent
      incontinence problems, are questioned.

PMID- 9537560
TI  - Impaired gastric emptying in children with repaired esophageal atresia: a
      controlled study.
AB  - BACKGROUND: Scintigraphy is considered the "gold standard" for investigating
      gastric emptying. The lack of standards regarding registration technique and meal
      composition has been a problem especially in pediatric patients. METHODS: In this
      study, gastric emptying of a solid meal was assessed by scintigraphy in 10
      patients with repaired esophageal atresia (5 to 10 years old), and the results
      were compared with those in 11 healthy control children (5 to 11 years old). The
      meal consisted of pancakes with a fixed energy composition labeled with Tc-99m.
      Fractional meal retention values were plotted as a function of time. RESULTS:
      Half-emptying time and lag phase values were longer in the patient group, whereas
      the emptying rate was slower and the retention values at 60 and 90 minutes were
      higher than in the control group. Extremely long lag phase and slow emptying
      rates were seen in two patients with reflux symptoms and abdominal complaints.
      Gastric emptying in healthy children has not previously been studied by
      scintigraphy. The results of this study show that values for gastric emptying of
      solids in healthy children correspond well to those reported in healthy adults.
      CONCLUSION: Scintigraphy is an easy and reliable method for gastric emptying
      studies in children. The radioactive dose can be kept very low, which makes it a
      safe method even for pediatric patients. Delayed gastric emptying can occur in
      patients who have repaired esophageal atresia, and may be associated with reflux
      symptoms and abdominal complaints.

PMID- 9537561
TI  - Multisystem organ failure and capillary leak syndrome in severe necrotizing
      enterocolitis of very low birth weight infants.
AB  - BACKGROUND: Classification systems for necrotizing enterocolitis (NEC) in preterm
      infants have been developed to define severity grades relevant for treatment and
      prognosis. Multisystem organ failure (MSOF) and capillary leak syndrome (CLS)
      also have prognostic value in these patients. The aim of this retrospective study
      was to investigate the incidence and predictive value of MSOF and CLS according
      to the classification criteria. METHODS: The records of 1,022 very low birth
      weight infants admitted from 1982 to 1996 were reviewed for diagnosis of NEC
      stage IIA or higher (classification of Walsh and Kliegman). Among those patients
      (n = 50) the incidence of MSOF and CLS was determined, separately for surgical or
      conservative treatment. RESULTS: Twelve patients were assigned to stage II, 22 to
      stage IIIa, and 16 to stage IIIb; 31 infants underwent operation. Mortality rate
      was not influenced by the grade. In eight patients only gastrointestinal symptoms
      were found, whereas in 23 patients, up to three organ systems and in 19 patients,
      four or more organ systems were affected. Mortality depended on the number of
      involved organ systems. CLS occurred postoperatively in 10 of the 31 infants;
      eight of them died. CONCLUSION: The prognostic values of MSOF and CLS are higher
      than that of classification criteria in NEC of VLBW infants.

PMID- 9537562
TI  - Staged silo repair of gastroschisis with preservation of the umbilical cord.
AB  - BACKGROUND: The optimal surgical approach for gastroschisis remains
      controversial, although primary closure after vigorous stretching of the
      abdominal wall and decompression of the intestinal contents is currently
      preferred. METHODS: Between 1984 and 1997, 24 newborns with gastroschisis were
      treated at Saitama Children's Medical Center. The average gestational age was
      37.3 weeks, and the average birth weight was 2,285 g. One patient had the
      associated anomaly of intestinal atresia and short bowel. Rupture of the
      intestines during delivery was noted in one patient. The authors applied their
      nonaggressive staged repair using a prosthetic silo with preservation of the
      umbilical cord in 20 of the 24 cases (83.3%). Primary closure with preservation
      of the umbilical cord was performed in the remaining four cases (16.7%). In these
      patients, the gastroschisis was mild. RESULTS: In the 20 cases treated by staged
      repair, the average interval between the first and second operation was 9.8 days.
      Mechanical ventilation was not required in 16 of 20 (80%) patients treated by
      staged repair, or in two of four (50%) patients treated by primary repair. The
      number of days to the first feeding averaged 14.6 days in 23 cases, excluding the
      patient with short bowel syndrome who required continuous total parenteral
      nutrition (TPN). TPN through a central venous catheter was required in 3 of 23
      patients (13.0%). The overall average hospital stay was 55.1 days. Survival was
      24 of 24 or 100%. Complications included perforation of the intestines, gastric
      bleeding, ventral hernia, and wound infection. No infections were associated with
      the prosthetic silo. All of the patients had a satisfactory cosmetic outcome.
      Recent advances in neonatal intensive care, including antibiotic therapy, reduced
      the possibility of infection. CONCLUSIONS: This staged repair of gastroschisis
      was simple and safe, neither requiring experienced surgical judgment nor
      complicated postoperative management, and achieved satisfactory results.
      Furthermore, preservation of the umbilical cord provided an improved cosmetic
      appearance.

PMID- 9537563
TI  - Exteriorization of the distal esophagus in the abdomen in esophageal atresia.
AB  - METHODS: The distal esophagus was exteriorized on to the left upper abdominal
      wall (abdominal esophagostomy) in 15 babies who had esophageal atresia with or
      without tracheo-esophageal fistula. The indications for this procedure were long
      gap atresia with or without tracheoesophageal fistula in which primary
      anastomosis was not possible and a major anastomotic dehiscence requiring
      cervical esophagostomy and gastrostomy. In all these patients a decision to
      replace the esophagus had been made, and a cervical esophagostomy was
      constructed. The distal esophagus was mobilized either from the thorax if
      thoracotomy had been done or by a transhiatal abdominal route. CONCLUSIONS:
      Advantages of the abdominal esophagostomy include absence of gastroesophageal
      reflux, no indwelling catheter, early institution of enteral feeds, intermittent
      catheterization for feeding, easy nursing care, and no stomal complications. In
      addition, this procedure allows the entire stomach to be available for esophageal
      replacement and retains the natural gastroesophageal junction and the lower
      esophagus for anastomosis to any bowel segment being used for the esophageal
      replacement.

PMID- 9537564
TI  - Pulmonary sequestrations: prenatal ultrasound diagnosis, treatment, and outcome.
AB  - BACKGROUND/PURPOSE: With the development of antenatal diagnosis of pulmonary
      sequestrations, the authors decided to define more accurate perinatal operative
      indications. METHODS/RESULTS: Antenatal ultrasound scanning (US) enabled the
      diagnosis of congenital pulmonary malformation in 10 cases between the twentieth
      and the thirty-third week of amenorrhea (WA; average, 26 WA). An absolute or
      relative regression of the thoracic mass size was observed in five patients. The
      systemic arterial blood supply was identified in four patients by Doppler US. Two
      fetuses required treatment. One of them suffered from a voluminous sequestration,
      larger than one hemithorax, with polyhydramnios. Three successive paracentesis of
      ascites and amniotic fluid allowed the pregnancy to continue until term. The
      second fetus had a sudden left hydrothorax at 30 WA and was treated by a
      pleuroamniotic shunt. Five spontaneous partial involutions of the mass during the
      antenatal period were observed. The 10 patients underwent surgery after birth.
      There was no mortality. Morbidity occurred in one case of antenatal treatment.
      Twenty-eight other cases of antenatal diagnosis of pulmonary sequestration have
      been described in the medical literature. Spontaneous involution of the mass has
      been reported in eight fetuses and its complete disappearance in two cases.
      Thirteen fetuses had polyhydramnios. Five of these progressed spontaneously
      without treatment; only two survived. Two other fetuses were drained or
      punctured, and one survived. Premature deliveries were undertaken for the six
      other fetus; there was one perinatal death. CONCLUSIONS: Sequestrations with
      polyhydramnios may be treated in an early prenatal period. Mortality and
      morbidity rates are still high. At birth, large-sized sequestrations (more than
      half a hemithorax) must be operated on, even in cases of no respiratory distress.
      Medium-sized sequestrations must be operated on to remove the mass. Small and
      asymptomatic sequestrations must be operated on in case of intralobar forms
      (often cystic), or with a big blood supply. The artery may be responsible for
      severe complications (hemoptysis, aneurysm).

PMID- 9537565
TI  - Serial lung volume measurements during the perinatal period in infants with
      abdominal wall defects.
AB  - METHODS: Daily measurements of lung volume (functional residual capacity, FRC)
      were made during the perinatal period in eight infants (median gestational age,
      37 weeks; range, 34 to 38 weeks) with abdominal wall defects. RESULTS: On the
      first day of life and before surgical intervention, four infants had FRCs below
      the reference range; the occurrence of low lung volumes was not significantly
      related to gestational age or diagnosis. Lung volume was further, but only
      temporarily, impaired by surgical closure of the abdominal wall defect, with a
      reduction in the median FRC from 25 mL/kg (range, 18 to 36) preoperatively to 12
      mL/kg (range, 5 to 19) on the first postoperative day (P < .02). CONCLUSION:
      These data are consistent with abnormal antenatal lung growth in certain infants
      with abdominal wall defects.

PMID- 9537566
TI  - Chylothorax after repair of congenital diaphragmatic hernia--risk factors and
      morbidity.
AB  - BACKGROUND/PURPOSE: Chylothoraces have been reported rarely after congenital
      diaphragmatic hernia (CDH) repair, but that is contrary to the authors'
      experience. The aim of this study was to audit the outcome of antenatally
      diagnosed CDH cases to determine the incidence, possible risk factors, and
      morbidity associated with chylothorax in CDH patents. METHODS: Twenty-four of 35
      consecutive infants with CDH (69%) underwent surgical repair and survived the
      immediate postoperative period. RESULTS: Effusions developed in all 22 for whom
      chest radiographs were available. Six of the eight infants whose effusions
      required drainage had a chylothorax. Those six infants required a mean of 8 days
      of thoracentesis, during which a mean total volume of 358 mL/kg of fluid was
      removed. The infants remained on a medium-chain triglyceride (MCT) formula for a
      mean of 81 days. The six infants with a chylothorax differed from the rest with
      respect to their duration of oxygen dependence (a median of 28.5 versus 15 days,
      P < .05) and hospital stay (a median of 5.5 versus 4 weeks, P < .05), but no
      significant risk factors for the development of a chylothorax were identified.
      CONCLUSION: Chylothorax is a relatively common cause of effusion after CDH repair
      and is associated with increased morbidity.

PMID- 9537567
TI  - All mechanical low rectal anastomosis in children.
AB  - PURPOSE: The aim of this study is to demonstrate the feasibility and usefulness
      of mechanical suturing in children for low rectal anastomosis. METHODS: The study
      group includes 31 children operated on from January 1993 to July 1996 by the same
      senior surgeon, performing the modified Duhamel procedure for Hirschsprung's
      disease in 17 children, intestinal neuronal dysplasia in seven, and the Knight
      Griffen procedure in seven pediatric patients with chronic ulcerative colitis.
      RESULTS: In all the cases the technique of "viscero-synthesis" was performed
      using the mechanical stapler. A circular stapler has been used for the end-to-end
      and the end-to-side anastomosis between the anal canal or the back wall of the
      rectum with the pulled viscus, while a linear endoscopic stapler (GIA) has been
      used for the consolidation of the rectocolic wall in the modified Duhamel
      technique. CONCLUSIONS: The results obtained demonstrate that the mechanical
      staplers in children are safe and effective in low rectal anastomosis, sparing
      operative time and reducing the risk of anastomotic dehiscence; however, the size
      of circular instruments limits its use in neonates and small infants.

PMID- 9537568
TI  - Congenital diaphragmatic hernia--does the side of the defect influence the
      incidence of associated malformations?
AB  - BACKGROUND/PURPOSE: Patients with congenital diaphragmatic hernia (CDH)
      frequently have associated anomalies. Experiments in the nitrofen CDH model have
      shown differential embryonic cell death patterns in rodents suggesting unique
      mechanisms in the formation of right-sided (RCDH) or left-sided (LCDH)
      diaphragmatic hernia. These findings provide insight into the pathogenesis of CDH
      and may aid our understanding on the spectrum of associated anomalies commonly
      observed in humans. This study therefore set out to test the hypothesis that the
      side of the diaphragmatic defect in humans is related to the incidence and
      severity of coexistent organ malformations. METHODS: The medical and autopsy
      records of 301 CDH patients presenting to two institutions over a 23-year period
      were examined to analyze these factors. RESULTS: One hundred patients (33%) were
      found to have one or more associated anomalies. The incidence of multiple-RCDH
      (10%) versus LCDH (7.3%) and cardiac anomalies-RCDH (10%) versus LCDH (8.5%) was
      similar in both groups of patients. However, the hypoplastic heart syndrome was a
      unique feature in 5 of 22 patients (23%) with LCDH who had cardiac abnormalities.
      This cardiac anomaly may be related developmentally to LCDH. CONCLUSION: The
      cellular mechanisms underlying the genesis of this spectrum of abnormalities in
      humans and the nitrofen CDH model warrant further study to elucidate factors
      governing embryonic cell fate and phenotype expression.

PMID- 9537569
TI  - Quality of life more than 20 years after repair of esophageal atresia.
AB  - PURPOSE: To examine the quality of life after repair of esophageal atresia,
      follow-up studies were performed in 58 of 71 surviving patients (81.7%). METHODS:
      Fifty patients with primary anastomosis and all eight surviving patients with
      colon interposition were seen. The mean age was 25.3 years (range, 20 to 31).
      Symptoms were evaluated by a standardized interview. Quality of life assessment
      was performed using a visual analogue scale (0 to 100 points), the Spitzer Index
      (5 dimensions, 10 points), and the Gastrointestinal Quality of Life Index (GIQLI,
      5 dimensions, 128 points). RESULTS: After primary anastomosis the estimated meal
      capacity was unrestricted in 46 patients (92%), but numerous symptoms such as
      recidivating cough (60%), hold up (48%), and short breath (30%) were reported.
      All symptoms except cough were seen more frequently in patients with colon
      interposition, and all of these patients suffered from periods of short breath.
      Quality of life scores were higher in patients with primary anastomosis compared
      with colon interposition. The difference in the visual analogue scale score did
      not reach statistical significance, but the mean Spitzer Index was 9.7 compared
      with 8.8 after colon interposition (P < .05). The GIQLI after primary anastomosis
      was similar to that in healthy controls and was significantly lower in patients
      with colon interposition. This was because of specific symptoms, which scored
      49.3 after colon interposition compared with 61.7 after primary anastomosis (P <
      .05) and to 54.8 (SD 5) in healthy controls (P < .05). Physical and social
      functions, emotions, and inconvenience of a medical treatment scored similar in
      patients with primary anastomosis, colon interposition, and healthy volunteers.
      CONCLUSIONS: The long-term quality of life after primary anastomosis was
      excellent. Patients with colon interposition suffer more frequently from various
      gastrointestinal and respiratory symptoms, but they lead an otherwise normal
      life.

PMID- 9537570
TI  - Segmental defect of the intestinal musculature associated with ileal atresia and
      biliary atresia.
AB  - A full-term baby boy with a segmental defect of the ileal musculature associated
      with terminal ileal and biliary atresia is presented. The newborn had a dilated
      loop of the ileum 30 cm proximal to the ileal atretic site. Pathological study
      results showed absence of the intestinal musculature with relatively intact
      mucosa. Foci of recent muscular necrosis were found in the lesion. One month
      later, relaparotomy was performed because of persistent jaundice and hepatic duct
      atresia was confirmed. Segmental defect of the intestinal musculature associated
      with ileal atresia and biliary atresia has not been reported in the literature.
      The authors emphasize that in the management of this unusual defect, one should
      pay attention to the multiple associated malformations.

PMID- 9537571
TI  - Urethral strictures after fulguration of posterior urethral valves.
AB  - This report discusses the incidence and predisposing factors for postfulguration
      urethral strictures in 82 boys with posterior urethral valves treated over 20
      years and followed up for a period ranging from 1 to 21 years. A urethral
      stricture developed in three of the 82 patients (3.6%). All newborns and infants
      with small urethral caliber at presentation were treated on a temporary tubeless
      diversion, and fulguration of the valves was deferred until 9 to 12 months of
      age. A 9F resectoscope with a loop electrode was used to fulgurate at 5, 7, and
      12 o'clock positions. A definite technical factor leading to a stricture could be
      identified in one of these three patients. Comparison of the "stricture" group
      with the "no stricture" group suggested that although dry fulguration did not
      have a definite correlation with stricture formation, it is best avoided.
      Refulguration and properly managed preoperative catheterization did not
      predispose to stricture formation. Meticulous surgical technique and avoiding
      oversized instrumentation were the most important factors for preventing this
      complication.

PMID- 9537572
TI  - Epignathus: report of a case with successful outcome.
AB  - Epignathus is an extremely rare form of teratoma that arises from the palate or
      pharynx in the region of the basisphenoid (Rathke's pouch). This condition is
      associated with a high mortality rate caused by severe airway obstruction in the
      neonatal period, thus requiring prenatal planning and prompt surgical treatment
      after birth. The authors describe a case of a giant epignathus that was
      successfully resected followed by an uneventful recovery.

PMID- 9537573
TI  - Intraabdominal leg: unique variant of split notochord syndrome.
AB  - An infant was born with a spectrum of anomalies representing a unique variant of
      the split notochord syndrome. The major anomalies included giant omphalocele and
      duplicated lower spine, between which developed a posterior lumbosacral mass that
      was contiguous with an intraabdominal, skin-covered "leg" within a saccular
      cecum. Features of this case overlap aspects of fetiform teratoma, fetus-in-fetu,
      conjoined twins, and caudal duplication, suggesting an etiologic relation between
      these entities and split notochord syndrome.

PMID- 9537574
TI  - Split notochord syndrome with prolapsed congenital colostomy.
AB  - A case of split notochord syndrome associated with a prolapsed colostomylike
      dorsal enteric opening, a foreshortened colon, imperforate anus, and meningocele
      is presented. The surgical management of this disorder is discussed and available
      literature is reviewed. The patient was successfully treated with a combined,
      single-stage surgical correction.

PMID- 9537575
TI  - Gastric diverticulum: an uncommon cause of abdominal pain in a 12 year old.
AB  - A 12-year-old girl presented with long-lasting intractable abdominal pain
      associated with a gastric diverticulum. The clinicopathologic features of this
      rare entity are discussed with emphasis on pathogenesis, diagnosis, and
      treatment. The authors emphasize that congenital diverticulum of the stomach
      should be considered in the differential diagnosis of abdominal pain in
      childhood. Surgical treatment consisting of simple excision of the diverticulum
      is warranted in cases presenting with long-lasting symptoms after failure of
      medical treatment.

PMID- 9537576
TI  - Sixth Japanese-German workshop on molecular and cellular aspects of
      carcinogenesis.

PMID- 9537577
TI  - Aberrant FHIT transcripts in squamous cell carcinoma of the uterine cervix.
AB  - The fragile histidine triad (FHIT) tumor suppressor gene at 3p14.2 has
      abnormalities in several types of human cancers. To investigate the potential
      role of FHIT in cervical cancer, which exhibits frequent loss of heterozygosity
      of 3p, we have examined primary cervical cancer samples from 28 patients for
      alterations of the FHIT gene. Abnormal FHIT transcripts were detected using
      reverse transcription-polymerase chain reaction (PCR) and subsequently by
      sequencing. Of 28 primary cervical carcinomas analyzed, 12 tumors (43%) showed
      abnormal FHIT transcripts, including deletion, insertion and point mutation. Loss
      of a FHIT transcript was observed in 2 cases (7%). Allelic loss of the FHIT gene
      was detected in 16 of 27 informative cases (59%). Oncogenic human papillomavirus
      (HPV) type 16, 18, 33, 35, 58 and 59 were not only present but were expressed in
      24 of 28 cases (85%) by consensus PCR-RFLP (polymerase chain reaction-restriction
      fragment length polymorphism) analysis for the HPV E6 and E7 genes. Our data
      indicate that alteration of the FHIT gene is an important genetic event
      associated with cervical cancer and oncogenic

PMID- 9537578
TI  - Reproductive factors and breast cancer in New Zealand.
AB  - A national population-based case-control study was used to assess the influence
      on breast cancer risk of reproductive factors and the possibility of an
      interaction with age at diagnosis. A total of 891 women aged 25 to 54 with a
      first diagnosis of breast cancer, and 1864 control subjects, randomly selected
      from the electoral rolls, were interviewed. There was a declining risk of breast
      cancer with increasing age at menarche (p = 0.06), the strongest effect being
      seen in women aged less than 40. Parous women had a 27% lower risk of breast
      cancer than nulliparous women, a reduced risk being evident in all but the
      youngest age group. A falling risk of breast cancer with rising parity was clear
      only in women diagnosed when aged at least 45 years. Breast cancer risk tended to
      fall amongst parous women with increasing duration of breastfeeding (p = 0.14);
      the association was most apparent in the youngest women, while those over 40
      years at diagnosis showed no clear negative trend. There was no association of
      breast cancer risk with age at first full-term pregnancy, time since last full
      term pregnancy, abortion (spontaneous or induced), abortion before first full
      term pregnancy, or ability to conceive, and there was no trend in risk with age
      at natural menopause. Women in the highest category of body mass index at age 20
      had the lowest risk of breast cancer in the age group studied. When each
      reproductive factor was formally tested for effect modification by age at
      diagnosis, the interaction term in logistic models approached statistical
      significance only for parity (p = 0.07).

PMID- 9537579
TI  - Expression of epidermal growth factor receptor in urinary bladder cancer
      metastases.
AB  - Bladder cancers frequently exhibit an increased number of epidermal growth factor
      receptors (EGFR) in comparison to normal urothelium. The EGFR could potentially
      be a target for toxic conjugates. The aim of our study was to compare the
      expression of EGFR in metastases with concurrent or primary tumour in the urinary
      bladder using immunohistochemical techniques and a monoclonal antibody. Tumour
      material from 20 patients was investigated. The majority (13/20) of the
      metastases were homogeneously stained and showed a moderate to strong membranous
      staining for EGFR. The expression of EGFR in primary bladder tumours and
      metastases was similar. There was no indication that tumour tissue exposed to
      chemotherapy or radiation had a decreased number of EGFR. Targeting of the EGFR
      thus seems potentially applicable to metastatic disease.

PMID- 9537580
TI  - Isolation and analysis of two strongly transforming isoforms of the Epstein-Barr
      Virus(EBV)-encoded latent membrane protein-1 (LMP1) from a single Hodgkin's
      lymphoma.
AB  - Two genes encoding the latent membrane protein 1 (LMP1) of the Epstein-Barr virus
      (EBV) were isolated from a single case of Hodgkin's disease (HD) and were tested
      for their biological activities. The LMP1 gene from the Reed-Sternberg cells
      contained point mutations relative to the prototype LMP1 gene, leading to amino
      acid exchanges. The LMP1 gene from passenger lymphocytes showed identical point
      mutations, but also had an in-frame insertion of 132 base pairs within the 33-bp
      repeat region. This insert encoding 44 amino acids contained the sequence PSQQS,
      corresponding to the potential TRAF-binding motif PXQXT/S. When compared to the
      B95.8 gene, both HD-derived LMP1 genes showed an increase in the transformation
      of Rat-1 rodent fibroblasts. The transforming ability of the LMP1 gene with the
      insertion was greater than that of the other HD-derived LMP1, and was comparable
      with the highly transforming LMP1-Cao gene derived from a nasopharyngeal
      carcinoma. The HD-derived genes stimulated expression of the cell-surface
      markers, CD40 and CD54, similarly to the LMP1-B95.8 gene, while the LMP1-Cao gene
      had a significantly reduced ability to induce these proteins. In contrast, the
      LMP1-Cao transactivated an NF-kappaB-response element more efficiently than did
      the HD-derived genes. Transfer of the 132-bp insert alone into the B95.8 gene did
      not increase its transforming activity to the LMP1-Cao level, indicating that
      additional mutations in the LMP1 gene are necessary for modulating this function.

PMID- 9537581
TI  - Sunlight and carcinogenesis: expression of p53 and pyrimidine dimers in human
      skin following UVA I, UVA I + II and solar simulating radiations.
AB  - DNA damage by UV radiation plays an essential role in skin cancer induction. We
      report that even sub-erythemal doses of solar simulating radiation, are capable
      of inducing substantial nuclear damage, namely pyrimidine dimers and p53
      induction in human skin in situ. The quantity and distribution of p53 induced in
      human skin by UV radiation depended highly on the waveband and dose of UV used.
      Solar simulating radiation induced very high levels of p53 throughout all layers
      in epidermal keratinocytes 24 hr following an erythemal dose (230+/-15.9/1000
      cells), and the induction followed a dose response. Following UVA I + II and UVA
      I radiations, p53 expression was approximately half of that seen with equivalent
      biological doses of solar simulating radiation (63.5+/-28.5 and 103+/-15.9,
      respectively). Expression of p53 was seen in basal cell keratinocytes at lower
      doses of UVA, but all layers of the epidermis were affected at higher doses.
      Pyrimidine dimer induction, however, was seen to be the same for equivalent
      biological doses of UVA I, UVA I + II and solar simulating radiations, which
      coincides with previous findings that pyrimidine dimers initiate the erythemal
      response and are implicated in skin carcinogenesis. When equivalent biological
      doses of pure UVA are used with no UVB contamination, significant nuclear
      alterations occur in human skin in situ, which can approach those seen with UVB
      radiation. Our results suggest that DNA damage assessed in vivo by
      immunohistochemistry could provide a very sensitive endpoint for determining the
      efficacy of protective measures, such as sunscreens or protective clothing,
      against both UVB- and UVA-induced damage in human skin.

PMID- 9537583
TI  - Analysis of FHIT transcripts in cervical and endometrial cancers.
AB  - Carcinoma of the uterine cervix is a common malignancy, and many affected women,
      have been found to exhibit loss of heterozygosity (LOH) in the chromosome 3p
      region. Recent studies have localized the FHIT (fragile histidine triad) gene in
      this region and also demonstrated a high frequency of abnormalities of this gene
      in various cancers. To determine the role of the FHIT gene in cervical and
      uterine carcinomas, 16 cases of cervical carcinoma and 7 cases of endometrial
      carcinoma, as well as nearby non-cancerous tissues in these patients, were
      analyzed by reverse transcription of the FHIT mRNA followed by polymerase chain
      reaction amplification and sequencing of the products. In this study, 13 of 16
      cervical cancers and 4 of 7 endometrial cancers displayed abnormal FHIT
      transcripts, including a lack of 2 or more exons of the FHIT gene, the insertion
      of several bases in the deletion junctions, and a 282 bp deletion from cDNA 171
      to 452, resulting in a frameshift. Moreover, 5 of 16 matched non-cancerous
      tissues from the cervical cancer patients and 4 of 7 non-cancerous tissues from
      endometrial cancer patients also showed the presence of abnormal transcripts
      lacking 3 or more exons of the FHIT gene. Only 1 of 23 paired samples exhibited
      LOH. Our results suggest that the abnormal transcript of the FHIT gene is common
      in both normal and tumor tissues of the uterus and cervix. We also checked for
      HPV infection in these samples and found no definite relationship between the
      abnormal transcript and human papillomavirus infection.

PMID- 9537582
TI  - Epstein-Barr virus strain variation in nasopharyngeal carcinoma from the endemic
      and non-endemic regions of China.
AB  - Nasopharyngeal carcinoma (NPC) occurs with a striking geographic incidence and is
      endemic in parts of southern China, where it is the major cause of cancer death.
      Epstein-Barr virus (EBV) is detected in all cells of the majority of NPC cases
      regardless of geographic origin. A small subset of EBV genes is expressed in NPC,
      including the latent membrane protein (LMP-1). LMP-1 is essential for
      transformation of B lymphocytes and is considered to be the EBV oncogene. This
      analysis of the DNA sequence variation within the LMP-1 gene reveals a consensus
      sequence for a strain, denoted China1, which predominates in East Asia where NPC
      is endemic. The China1 strain is characterized by nucleotide changes at 13 loci
      in the amino terminal portion of the LMP-1 gene when compared with the B95-8
      prototype, including a point mutation resulting in the loss of an Xho1
      restriction site. This strain was present in 9 of 15 NPC biopsy specimens from
      the endemic region and in 7 of 13 from northern China, where NPC is non-endemic.
      A second strain, China2, was detected in 4 of 15 endemic isolates and in 2 of 13
      non-endemic isolates; this strain was characterized by a cluster of 5 nucleotide
      changes in the amino terminal portion of LMP-1 in addition to those seen in
      China1. It was also marked by distinct changes in the carboxy terminal region of
      LMP-1 including the retention of amino acids 343-352. All China1 isolates were
      EBV type 1, whereas the China2 isolates did not correlate with EBV type.
      Phylogenetic relationships between these 2 strains were determined, as were
      signature amino acid alterations that discriminate between them.

PMID- 9537584
TI  - Expression of a kinase-deficient IGF-I-R suppresses tumorigenicity of
      rhabdomyosarcoma cells constitutively expressing a wild type IGF-I-R.
AB  - Previous results have shown that the insulin-like growth factor type I receptor
      (IGF-I-R) plays a critical role in the control of rhabdomyosarcoma (RMS) growth.
      The purpose of this study was to investigate whether a mutated IGF-I-R, when
      expressed in RMS cells, may interfere with the function of the endogenous wild
      type IGF-I-R. We also examined whether the expression of a mutated IGF-I-R may
      induce phenotypic changes in RMS cells. We used here the mutated IGF-I-R with a
      lysine to arginine residue 1003 substitution, called IGF-I-KR, which carries a
      mutation in the ATP-binding domain of the intracellular beta subunit, while the
      extracellular, ligand binding alpha subunit remains unchanged. We observed that
      the expression of this mutated IGF-I-KR markedly decreased the response of RMS
      cells to stimulation with IGF-I. While stimulation with IGF-I increases the
      autophosphorylation of IGF-I-R in the parent cells, stimulation with IGF-I failed
      to produce a comparable increase in autophosphorylation in the cells expressing
      the mutated IGF-I-KR. We also observed a decreased plating efficiency of cells
      expressing the mutated IGF-I-KR. Consistently, a decrease of RMS growth in vivo
      was observed in an animal model. Our data suggest that the IGF/IGF-I-R signaling
      pathway may be inhibited by expressing a mutated IGF-I-KR and that such a mutant
      gene could be utilized in developing novel therapeutic strategies to suppress RMS
      growth. 1998.

PMID- 9537585
TI  - Slow rate of free radical scavenging in the gastric antral mucosa of male Wistar
      rats: a possible mechanism of gastric carcinogenesis induced by N-methyl-N'-nitro
      N-nitrosoguanidine.
AB  - We previously suggested that hydroxyl free radical (-OH) production may play a
      role in carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG).
      MNNG-induced gastric cancer in rats and human gastric carcinoma occur most often
      in the antral mucosa and rarely in the normal fundic mucosa. We hypothesized that
      regional differences in anti-oxidant activity may be responsible. In the present
      study, we examined anti-oxidant activity by comparing the relative rates of
      reduction of a nitroxide free radical, 4-hydroxy-2,2,6,6-tetramethyl-1
      piperidinyloxy (Tempol), in the antral and fundic mucosa of male Wistar rats
      using ESR. The relative rate of Tempol reduction was significantly slower in the
      antral portion of the wall than in the fundic portion when Tempol [4 x 10(-6)
      mole/mg wet weight of gastric wall] in HEPES buffer (pH 7.4) was spread over the
      mucosal surface of a section of the gastric wall. Addition of a sulfhydryl group
      modulator, N-ethylmaleimide, to the mucosal surface before treatment with Tempol
      removed the significant difference observed in the rates of reduction in the
      antral and fundic portions of the gastric wall. No signals were detected in the
      muscle layer. Our results indicate that the relative rate of free radical
      reduction by sulfhydryl groups was significantly slower in the antral mucosa than
      in the fundic mucosa. We therefore conclude that a regional difference in the
      rates of reduction of free radicals by sulfhydryl groups may result in the site
      susceptible to development of MNNG-induced gastric cancer.

PMID- 9537586
TI  - Construction and characterization of a bispecific diabody for retargeting T cells
      to human carcinomas.
AB  - We describe the construction of a recombinant bispecific antibody fragment in the
      diabody format with specificity for both the well-established human pancarcinoma
      associated target antigen EGP2 (epithelial glycoprotein 2, also known as the CO17
      1A antigen or KSA) and the CD3epsilon chain of human TCR/CD3 complex. The murine
      anti-EGP2 (MOC31) single chain variable fragment (scFv) and the humanized anti
      CD3 (Ucht1v9) scFv were cast into a diabody format (designated Dia5v9) using a
      short 5 amino acid Gly-Ser linker between immunoglobulin heavy-chain and light
      chain variable domains. Purification of the poly-histidine tagged Dia5v9 was
      achieved from extracts of protease deficient Escherichia coli by IMAC
      chromatography. The Dia5v9 diabody showed strong binding to both EGP2 and CD3 in
      transfected cells. The in vitro efficacy of Dia5v9 in mediating tumor cell lysis
      by interleukin-2 activated human T cells appeared to be similar to that of the
      hybrid-hybridoma-derived BsF(ab')2 Bis1 (anti-EGP2/anti-CD3) in a standard 4-hr
      51Cr-release assay. This small and partially humanized recombinant bispecific
      antibody fragment may be valuable for T-cell-based immunotherapeutical treatment
      protocols, retargeting activated peripheral blood T lymphocytes to lyse various
      human carcinomas in vivo.

PMID- 9537587
TI  - Hepatocyte growth factor/scatter factor stimulates chemotaxis and growth of
      malignant mesothelioma cells through c-met receptor.
AB  - Hepatocyte growth factor (HGF) and its receptor c-met are present in several
      human tissues but their expression in mesothelial cells has not been examined. In
      this study, we have investigated the expression of HGF and c-met in normal human
      mesothelial cells and 11 human malignant mesothelioma cell lines. Using RT-PCR
      and Western blotting we found that HGF is produced by 3/11 mesothelioma cell
      lines whereas c-met is expressed in 11/11 mesothelioma cell lines. In addition, c
      met expression was also found in 6/6 cell samples obtained from pleural fluids of
      patients with mesothelioma. In contrast, neither normal cultured mesothelial
      cells nor mesothelial cells obtained directly from patients without mesothelioma
      expressed HGF nor c-met. We have also analysed the biological function of HGF and
      c-met in mesothelioma cell lines. Recombinant human (rh) HGF stimulated both
      directional (chemotactic) and random (chemokinetic) motility in all mesothelioma
      cell lines tested. Furthermore, mesothelioma serum free conditioned medium
      containing HGF stimulated mesothelioma cell migration. This effect could be
      blocked in the presence of neutralizing anti-HGF monoclonal antibodies (MAbs) in
      the assay. Addition of HGF to mesothelioma cells cultured on collagen type IV was
      associated with induction of bipolar shape and protrusion of prominent
      pseudopodia. We have also found that rhHGF was mitogenic for mesothelioma cells.
      Our findings suggest that expression of HGF/c-met is involved not only in
      mesothelioma progression but also in its growth and migration and that c-met
      expression found in mesothelioma cells taken directly from patients may be of
      diagnostic importance.

PMID- 9537588
TI  - Dendritic cells fused with mastocytoma cells elicit therapeutic antitumor
      immunity.
AB  - Characterization of the spontaneous immune response that frequently occurs in
      tumor-bearing animals, as well as immunization using dendritic cells pulsed with
      tumor antigens, suggests that a limiting factor of the tumor-specific immune
      response may be a defect in the co-stimulatory signal that is required for
      optimal activation of T cells. In this work, we describe a new approach to
      improve the antigen-presenting capacity of tumor cells, which does not require a
      source of purified tumor-associated antigen. We fused P815 mastocytoma cells with
      bone marrow-derived dendritic cells. We obtained one hybrid that displayed the
      phenotypic and functional properties of dendritic cells and expressed mRNA coding
      for the tumor-associated antigen P815 A/B. Injections of irradiated hybrid cells
      prevented the growth of preimplanted mastocytoma and induced long-lasting tumor
      resistance.

PMID- 9537589
TI  - Induction of wild-type p53, Bax, and acidic endonuclease during somatostatin
      signaled apoptosis in MCF-7 human breast cancer cells.
AB  - Somatostatin (SST) analogs inhibit tumor cell growth by exerting direct anti
      proliferative effects with cytostatic (growth arrest) or cytotoxic (apoptosis)
      consequences. The SST analog SMS 201-995 (octreotide, OCT) inhibits growth of MCF
      7 human breast adenocarcinoma cells, which express multiple SSTRs. Its action has
      been reported to result in either apoptosis or growth arrest, but the underlying
      mechanisms have not been elucidated in this tumor cell model. Here, we report
      that OCT elicits cytotoxic response in these cells, leading to apoptosis, which
      is associated with a rapid, time-dependent induction of wild-type p53 and an
      increase in Bax. There was no G1 cell-cycle arrest in these cells during OCT
      treatment as suggested by the decrease in G1/S ratio and the lack of induction of
      pRb and p21. Additionally, we demonstrate that OCT-induced DNA fragmentation in
      this cell line is due to selective activation of a cation-insensitive acidic
      endonuclease. Our data provide a rationale for utilizing SST analogs to treat
      SSTR-positive breast cancer cells expressing wild-type p53.

PMID- 9537590
TI  - Inhibition of stromal matrix metalloproteases: effects on breast-tumor promotion
      by fibroblasts.
AB  - Co-injection of fibroblasts with human epithelial breast-tumor MCF7 cells in the
      presence of Matrigel enhances tumor growth in nude mice. While most of the matrix
      metalloproteinases (MMPs) have been shown to be produced by stromal cells, tumor
      cells such as MCF7 cells are unable to produce MMPs. We therefore, hypothesized
      that the tumor-promoting effect of fibroblasts could be related to their
      production of MMPs. In order to inhibit stromal proteases, over-production of
      TIMP-2 was induced in MCF7 cells by in vitro retroviral-mediated gene transfer.
      TIMP-2-producing MCF7 cells were then co-injected with fibroblasts into nude
      mice. Alternatively, we evaluated the effect of Batimastat, a synthetic inhibitor
      of MMPs, on the tumorigenicity of MCF7 cells co-inoculated with fibroblasts into
      nude mice. Both physiological (TIMP-2) and synthetic (Batimastat) inhibitors of
      MMPs were able to abolish the tumor-promoting effect of fibroblasts. On the
      contrary, they failed to modulate the tumorigenicity of MCF7 cells injected
      alone. Interestingly, Matrigel from which low-molecular-weight proteins or growth
      factors had been removed failed to favor the tumorigenicity of MCF7 cells
      inoculated with fibroblasts. These findings emphasize the importance of
      fibroblasts in cancer progression, and suggest that their role could be related
      at least in part to production of proteases which can induce the release of
      factors from the extracellular matrix.

PMID- 9537591
TI  - Repeated treatment with antibody-targeted superantigens strongly inhibits tumor
      growth.
AB  - Superantigens (SAg) are microbial proteins with the capacity to activate a large
      proportion of T cells. We have developed a novel approach for cancer
      immunotherapy by genetically fusing the SAg staphylococcal enterotoxin A (SEA) to
      a Fab-fragment of a tumor-specific antibody. Repeated exposure to SEA induces a
      state of unresponsiveness including cell deletion and functional
      hyporesponsiveness, i.e., anergy. In this study we have developed improved
      therapeutic schedules to allow repeated injections of Fab-SEA, limit development
      of immunological unresponsiveness and promote maximal anti-tumor response. Four
      daily injections of Fab-SEA to mice carrying B 16-C215 lung metastases resulted
      in 90-95% reduction in the number of metastases. However, the animals did retain
      a minimal residual tumor disease. The immune system was in a hyporesponsive state
      after 4 daily Fab-SEA injections, and further injections did not improve therapy.
      Two repeated cycles, each comprising 4 daily injections of Fab-SEA, significantly
      prolonged the survival and resulted in complete cure of a fraction of the
      animals. A rest period of 10 days between the cycles was required to mount an
      efficient secondary anti-tumor response. This secondary immune response was
      characterized by partial recovery of cytokine production i.e., interleukin-2,
      interferon-gamma and tumor necrosis factor-alpha. Strong CTL activity was
      detected in animals that had rested for 8 weeks between the 2 cycles.
      Interestingly, irrespective of the resting period, the CD4+ SEA-reactive T cells
      expanded in response to all 4 additional Fab-SEA injections both locally and in
      spleen. In contrast, only marginal expansion of CD8+ T cells was seen if
      restimulation was given within 1 month. Our data show that potent anti-tumor
      effector functions can be induced after repeated stimulation cycles with a SAg
      monoclonal antibody fusion protein resulting in a CD4+ T cell-dependent cytokine
      release, prolonged survival and induction of complete cures.

PMID- 9537592
TI  - Histo-blood group A/B antigen deletion/reduction vs. continuous expression in
      human tumor cells as correlated with their malignancy.
AB  - Deletion or reduction of histo-blood group A or B antigen in tumors of A or B
      individuals is clearly correlated with the degree of malignancy and metastatic
      potential in many types of human cancer. Haptotactic motility of A+H- or B+H-
      colonic or gastric tumor cell lines produced by transfection of A or B gene was
      significantly lower than that of parental A-H+ or B-H+ cells. This is ascribable
      to reduced function of alpha3 or alpha6/beta1 integrin receptor as we have
      recently shown. However, phenotypic changes resulting from gene transfection may
      not reflect physiological states associated with deletion or reduction vs.
      continuous expression of A or B antigen in tumors. We now describe the separation
      and phenotype characterization of A- cells from A+ tumor cell lines derived
      originally from colonic tumors of patients with histo-blood group A. A+ and A-
      populations were detected in originally A+ tumor cell lines SW480 and HT29. A-
      separated from A+ populations isolated from SW480 and HT29 were characterized by
      greatly enhanced haptotactic motility associated with reduced or deleted A
      expression at alpha3, alpha6, and beta1 integrin receptors which control cell
      motility. Nevertheless, expression of integrin receptors at the surface of A
      populations is the same as that for A+ populations for both SW480 and HT29 cells.
      Thus, A vs. H glycosylation in integrin receptors may alter their haptotactic
      function. Cell proliferation as reflected by 3H-thymidine incorporation was also
      reduced significantly in A+ as compared to A- populations. Our findings indicate
      that the degree of haptotactic motility and proliferation of colonic tumor cells
      are physiologically associated with the deletion or reduction vs. continuous
      expression of the histo-blood group A antigen.

PMID- 9537593
TI  - Neutralizing anti-vascular endothelial growth factor antibody completely inhibits
      angiogenesis and growth of human prostate carcinoma micro tumors in vivo.
AB  - BACKGROUND: Neovascularization mediated by growth factors produced by tumors is
      critical for the growth of tumors. Vascular endothelial growth factor (VEGF) is
      one such growth factor. A neutralizing anti-VEGF antibody (A4.6.1) was recently
      shown in vivo to inhibit tumor angiogenesis and growth of the human
      rhabdomyosarcoma cell line A673. The antibody profoundly changed the growth
      characteristics of the tumor line from a rapidly growing malignancy to a dormant
      microcolony. METHODS: In the present study, we evaluated the effects of A4.6.1
      (100 microg twice weekly, i.p.) on growth and angiogenic activity of spheroids of
      the human prostatic cell line DU 145 (diameter 700 microm at implantation)
      implanted in dorsal skinfold chambers in nude mice (n = 11). An antibody of the
      same isotype (n = 5) or saline (n = 5) was used as control. Tumor cells were
      prelabeled with a fluorescent vital dye (CMTMR), which allowed measurement of
      size of the implanted tumor spheroids throughout a two week observation period.
      FITC-dextran was used for plasma enhancement to visualize angiogenic activity.
      RESULTS: Tumors of control animals induced a neo-vasculature with high vascular
      density (350+/-12 cm[-1]). In animals treated with the anti-VEGF antibody, there
      was complete inhibition of neovascularization of the micro tumors and complete
      inhibition of tumor growth after the initial prevascular angiogenesis independent
      growth phase. CONCLUSIONS: These results demonstrate that inhibition of the key
      regulatory paracrine growth factor for endothelial cells, VEGF, results in
      complete suppression of prostate cancer induced angiogenesis and prevents tumor
      growth beyond the initial prevascular growth phase.

PMID- 9537594
TI  - Identification of binding proteins for PSP94 in human prostate adenocarcinoma
      cell lines LNCaP and PC-3.
AB  - BACKGROUND: Prostatic secretory protein of 94 amino acids (PSP94) is one of the
      predominant proteins found in human seminal fluid. Limited information is
      available regarding a physiological function for PSP94. An important step in the
      elucidation of this function is the determination of the mechanism of interaction
      of PSP94 with potential cellular targets. METHODS: Equilibrium binding assay was
      employed to demonstrate specific binding of biotinylated-PSP94 to the LNCaP and
      PC-3 cell lines. Binding proteins were partially purified by PSP94 affinity
      chromatography from LNCaP, PC-3 cells, and prostate tissues. RESULTS: Binding of
      biotinylated-PSP94 to LNCaP and PC-3 cells was saturable and time and temperature
      dependent. The binding could be specifically competitively inhibited by
      unlabelled PSP94. Two types of PSP94 binding sites with distinct affinity (Kd)
      and density (Bmax) were determined by Scatchard analysis for each of the two cell
      lines. For the LNCaP cells, these values were Kd 1 = 0.75 nM and Bmax1 = 300
      fmol/mg protein and Kd 2 = 4.5 nM, Bmax2 = 780 fmol/mg protein, respectively.
      Similar affinity and density results were obtained for PC-3 cells: Kd 1 = 0.83
      nM, Bmax1 = 250 fmol/mg protein, and Kd 2 = 5.0 nM, Bmax2 = 700 fmol/mg. The
      binding of biotinylated-PSP94 to the LNCaP cells was competitively inhibited by
      the partially purified proteins. Analysis of these proteins SDS-PAGE showed three
      main bands and the molecular weights of these three bands were approximately 180,
      100 and 60 kD, respectively. CONCLUSIONS: The data showed the presence of
      specific binding proteins to the PSP94 in LNCaP, PC-3 cells, and prostate tissue.

PMID- 9537595
TI  - Relative activity and specificity of promoters from prostate-expressed genes.
AB  - BACKGROUND: To evaluate their relative activity and specificity for prostate
      cells promoter and regulatory regions from three prostate-expressed genes
      prostate-specific antigen (PSA), probasin, and relaxin H2-have been compared in
      prostate cell lines and in lines of breast, bladder, liver, kidney, lung, and
      ovarian origin. METHODS: After transfection into different cell types, the
      activity of promoters was assayed using linked reporter genes and normalized
      against that of the Rous sarcoma virus. Activity was measured both in the
      presence and in the absence of co-transfected androgen receptor (AR). RESULTS:
      PSA and probasin regulatory regions showed strong responsiveness to co
      transfection of the AR in most cell types. The core PSA promoter region showed
      low activity and specificity, but the specificity and level of expression were
      substantially increased by inclusion of upstream sequences, particularly the
      enhancer region. Probasin promoter fragments showed specificity of expression for
      prostate cell lines but required AR for significant levels of expression. Relaxin
      promoter fragments directed significant AR-inducible expression in prostate cells
      but showed little specificity and variable AR responsiveness in other cell types.
      CONCLUSIONS: Of regulatory regions tested, a 430-base pair probasin promoter and
      PSA enhancer/core promoter showed the best combination of AR-stimulated prostate
      cell expression with limited expression in other cell types.

PMID- 9537597
TI  - Epidermal growth factor in the rat prostate: production, tissue content and
      molecular forms in the different prostatic lobes.
AB  - BACKGROUND: Epidermal growth factor (EGF) induces proliferation in prostate
      epithelial and stromal cells in primary culture. This investigation was set up to
      characterize the time and spatial expression of EGF in the rat prostate. METHODS:
      The expression of EGF was characterized in the distinct lobes of the rat prostate
      by means of ELISA, gel filtration, immunohistochemistry, and in situ
      hybridization. RESULTS: Local synthesis of EGF by the luminal epithelium was
      demonstrated by in situ hybridization in the dorsal lobe only. This lobe
      contained the major part of the prostatic EGF with a sixfold higher concentration
      than measured in the lateral lobe, and 300-fold higher than in the ventral lobe.
      Rat prostatic EGF was found to consist of at least two high-molecular-weight
      forms, as well as a 6-kDa form. The high-molecular-weight forms made up
      approximately 40% of the EGF measured in the dorsal rat prostate. At 8-12 weeks
      of age, the concentration of EGF in the dorsal lobe was doubled, with no further
      increase up to 16 weeks. CONCLUSIONS: We report a 300-fold difference in the
      lobar content of EGF in the rat prostate, and a doubling of the concentration at
      8-12 weeks of age.

PMID- 9537596
TI  - Melatonin receptors in benign prostate epithelial cells: evidence for the
      involvement of cholera and pertussis toxins-sensitive G proteins in their signal
      transduction pathways.
AB  - BACKGROUND: Melatonin, the hormone secreted nocturnally by the pineal gland,
      binds to epithelial cells from the human benign prostate, and can reduce their
      growth and viability. The possible involvement of GTP binding proteins cyclic
      adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) in
      melatonin responses in these cells were investigated. METHODS: The effects of
      melatonin on cAMP and cGMP were assessed in prostate cells untreated or
      pretreated with pertussis toxin (PTX) or cholera toxin (CTX). RESULTS: Melatonin
      augmented cAMP but reduced cGMP in the epithelial cells (maximal responses at 10
      nM). The increase in cAMP was attenuated by PTX, but not by CTX, whereas the
      decrease in cGMP was attenuated by CTX, but not by PTX. CTX, but not PTX,
      abolished the melatonin-mediated suppression of 3H-thymidine incorporation. In
      addition, melatonin facilitated the CTX- and PTX-mediated ADP ribosylation of 44-
      and 41-kilodalton proteins, respectively. The cGMP analogue 8-bromo-cGMP, negated
      the melatonin-mediated decrease in 3H-thymidine incorporation, whereas H89, a
      protein kinase A inhibitor, did not inhibit melatonin's effect. CONCLUSIONS:
      Melatonin receptors in the human benign prostate epithelial cells enhance cAMP
      and inhibit cGMP through PTX- and CTX-sensitive G proteins, respectively. The
      decrease in DNA synthesis may be secondary to the melatonin-mediated decrease in
      cGMP.

PMID- 9537598
TI  - Effects of linomide on advanced prostate-seminal vesicle cancers in Lobund-Wistar
      rats.
AB  - BACKGROUND: Angiogenesis and antiangiogenesis, as applied to oncology, are
      phenomena in which (1) tumors acquire a new blood vascular system from the host
      that is needed for their growth progression and metastasis; and (2) factors are
      produced that interfere with neovascularization, thereby inhibiting growth and
      metastasis of the tumor. Linomide, a chemical antiangiogenesis agent, inhibited
      the growth of transplanted tumors in mice and rats and inhibited the early
      development of metastasizing tumors induced in the prostate-seminal vesicle (P
      SV) complex of genetically susceptible Lobund-Wistar (L-W) rats. METHODS: L-W
      rats with small induced P-SV tumors were treated with a recommended dosage of
      linomide (100 mg/kg BW/day) by the intraperitoneal and oral routes. The rats were
      monitored for the next 1-2 months, and the primary and metastatic tumors were
      compared with related data in drug-free tumor-bearing control rats. RESULTS: P-SV
      tumors in linomide-treated and untreated control rats continued to grow, except
      that in the former (1) the tumors were marginally smaller, (2) the centers of the
      primary P-SV tumors had failed to grow, (3) the peripheral areas of the tumors
      contained actively proliferating tumor cells, and (4) metastatic P-SV tumors in
      the lungs were disrupted with focal areas of necrosis, but areas of intact tumor
      cells survived. Spread of tumor cells into the peritoneal cavity was not
      inhibited. Rats on orally administered linomide lived significantly longer than
      rats inoculated by the intraperitoneal route and untreated control rats. The
      dosage of linomide used showed evidence of toxicity. CONCLUSIONS: Although
      primary and metastatic P-SV tumors were damaged in L-W rats treated with
      linomide, this antiangiogenic drug was of minimal therapeutic benefit to rats in
      which a palpable P-SV tumor had developed before onset of treatments.

PMID- 9537599
TI  - Diagnoses rendered on prostate needle biopsy in community hospitals.
AB  - BACKGROUND: Reported incidences of various diagnoses made on needle biopsy of the
      prostate vary significantly in the literature, most of which has originated from
      large, academic medical centers. METHODS: We recorded all the prostate needle
      biopsy results from three community hospitals for 1990-1993 to determine the
      rates of, and trends in, various diagnoses in these practices. RESULTS: Hospital
      H1 (1,192 cases) halved the rate of atypical, nondefinitive diagnoses from 11.8%
      in 1990 to 5.7% in 1993 (P < 0.001). The rate at H2 (2,792 cases) remained
      essentially unchanged at 5.95+/-0.55%, and H3 (1,306 cases) went from 2.3% to
      6.0% (0.1 < P < 0.2). In the setting of an atypical, nondefinitive diagnosis, H1
      and H2 recommended repeat biopsy less than 7% of the time. H3 made this
      recommendation in an average of 22.1% of atypical cases. Annual rates of high
      grade prostatic intraepithelial neoplasia (PIN) showed no trend over time, and
      averaged 2.0% (1.2-3.25%) at H1 and 1.2% (0.3-2.0%) at H2. The diagnosis was
      never made at H3. The fraction of cancers diagnosed as low-grade (Gleason sum <
      or = 4) showed a statistically significant decreasing trend over time at all
      three hospitals (P < 0.05). These data are compared with those from the Johns
      Hopkins Hospital (JHH), a large academic center in geographic proximity to
      hospitals H1-H3. CONCLUSIONS: At these three community hospitals, we discerned
      (1) convergence to a rate of approximately 6.0% of atypical, nondefinitive
      diagnoses; and (2) a progressively more appropriate fraction of carcinomas
      diagnosed as low-grade on needle biopsy. The rates of diagnosis of high-grade PIN
      and recommendation of repeat biopsy varied. These rates of PIN, atypical,
      nondefinitive diagnoses, and low-grade cancer represent an assessment of
      diagnostic habits.

PMID- 9537600
TI  - 5-fluorouracil and low-dose recombinant interferon-alpha-2a in patients with
      hormone-refractory adenocarcinoma of the prostate.
AB  - BACKGROUND: The effectiveness of a chemotherapy regimen including 5-fluorouracil
      (5-FU) and recombinant interferon-alpha-2a (rIFN-alpha-2a) was evaluated in
      hormone-refractory prostate cancer patients. METHODS: Patients received a
      continuous intravenous infusion of 5-FU at 600 mg/m2/day for 5 days (D1-D5),
      followed by a bolus injection of 5-FU on D15 and D22. Patients received
      intramuscular injection of rIFN-alpha-2a at 3 million IU on D1, D3, D5, D15, and
      D22. This schedule was repeated every 4 weeks. RESULTS: Between 1993 and 1995, 23
      patients with hormone refractory prostate cancer were enrolled in this study. Two
      of five patients with nodal disease exhibited partial responses according to the
      NPCP criteria. Fourteen of 17 patients with bone disease showed stable disease.
      Of 21 patients assessible for response, 9 patients had a decrease in the PSA
      level greater than 50% of baseline. Bone pain disappeared partially or completely
      in 8 of 14 patients with this symptom at entry. The median overall survival was
      18 months. The associate toxicity was well tolerable. CONCLUSIONS: Combination
      chemotherapy of 5-FU and low dose rIFN-alpha-2a in patients with hormone
      refractory prostate cancer proved feasible, and with acceptable toxicity.

PMID- 9537601
TI  - Expression, structure, and function of androgen receptor in advanced prostatic
      carcinoma.
AB  - BACKGROUND: Endocrine therapy for prostate cancer aims to reduce the levels of
      circulating androgen or to inhibit androgen action by blocking the androgen
      receptor in the prostate, or both. Studies in various animal and human prostate
      cancer models suggested that there may be a downregulation of androgen receptor
      during prostate cancer progression. Recent work, however, showed androgen
      receptor expression in all stages of prostate cancer. The presence of mutant
      androgen receptors in a portion of prostate cancers and receptor activation in
      the absence of androgen or in the presence of low androgen concentrations is
      discussed within this context. METHODS: This review attempts to summarize the
      literature on androgen receptor expression in vitro and in vivo, as well as
      structural and functional alterations and communication between androgen signal
      transduction cascade and other signaling pathways. CONCLUSIONS: Prostate tumors
      adapt to an environment with low androgen supply by using a hyperactive androgen
      receptor. The mechanisms involved are mutations of the androgen receptor
      generating receptors with broadened activation spectrum, increased receptor
      expression, and activation by interaction with other signaling pathways.

PMID- 9537602
TI  - Isolation and androgen regulation of the human homeobox cDNA, NKX3.1.
AB  - BACKGROUND: The prostate is dependent on androgens for development and
      maintenance of its differentiated phenotype. We have applied the technique of
      differential display PCR to the androgen-sensitive prostate cancer cell line
      LNCaP to isolate androgen-responsive genes. METHODS: The technique of DD-PCR was
      applied to androgen-stimulated LNCaP cell RNA to detect and isolate androgen
      responsive genes. RESULTS: The human homeobox gene NKX3.1, the homologue to mouse
      Nkx3.1, recently isolated by Beiberich et al. [J Biol Chem 1996;271:31779-31782],
      was detected and cloned. NKX3.1 is induced by androgens in a time- and
      concentration-dependent manner. NKX3.1 is induced 6- to 7-fold in 12 hr, with a
      significant induction seen in 2 hr. This regulation is at the level of
      transcription, as androgens increase the number of new NKX3.1 transcripts, and de
      novo protein synthesis is not required. In humans, NKX3.1 is expressed most
      highly in the prostate, with a much lower level of expression seen in the testis.
      No other tissue examined showed detectable levels of NKX3.1 expression.
      CONCLUSIONS: NKX3.1 is an androgen-regulated, prostate-specific homeobox gene. We
      hypothesize that it may play a role in the development and differentiation of the
      prostate.

PMID- 9537603
TI  - Women's dietary calcium requirements are not increased by pregnancy or lactation.

PMID- 9537604
TI  - Food iron availability: back to the basics.

PMID- 9537605
TI  - Influence of human obesity on the metabolic fate of dietary long- and medium
      chain triacylglycerols.
AB  - The metabolic fate of an oral long-chain-triacylglycerol (LCT) load and of a
      mixed oral LCT and medium-chain-triacylglycerol (MCT) load was followed for 6 h
      in eight control and eight obese subjects with normal postabsorptive
      triacylglycerol concentrations. Labeled triacylglycerol and indirect calorimetry
      were used. Results showed that LCTs were less oxidized in obese than in control
      subjects (3.2+/-0.5 compared with 6.0+/-0.4 g, P < 0.01). Moreover, the amount of
      LCT oxidized was negatively correlated with fat mass (r = -0.77, P < 0.01).
      Appearance in plasma of dietary triacyglycerol-derived long-chain fatty acids was
      blunted in obese subjects and it was negatively related to fat mass (r = -0.84, P
      < 0.01) and positively to LCT oxidation (r = 0.70, P < 0.01). On the contrary,
      MCT oxidation was not altered in obese subjects compared with control subjects.
      Furthermore, the proportion of MCTs oxidized was higher in both groups compared
      with LCTs (x+/-SEM: 57.5+/-2.6% compared with 15.2+/-1.6%, P < 0.01, n = 16). Our
      conclusion is that obesity is associated with a defect in the oxidation of
      dietary LCTs probably related to an excessive uptake by the adipose tissue of
      meal-derived long-chain fatty acids. MCTs, the oxidation of which is not altered
      in obesity, could therefore be of interest in the dietary treatment of obesity.

PMID- 9537606
TI  - Predictors of overweight and overfatness in a multiethnic pediatric population.
      Child and Adolescent Trial for Cardiovascular Health Collaborative Research
      Group.
AB  - The goal of the study was to determine whether overweight or overfatness were
      predicted from sex, race or ethnicity, school site, and intervention or control
      status for children who were 9 y old at the outset of the Child and Adolescent
      Trial for Cardiovascular Health (CATCH). In this ethnically and geographically
      diverse group of 5106 students, height, weight, and triceps skinfold thickness
      were measured at 9 (baseline) and 11 y (follow-up) of age. The strongest
      predictors of status at follow-up were baseline overweight (odds ratio: 69.0; 95%
      CI: 54.9, 96.3) and overfatness (odds ratio: 27.4; 95% CI: 22.4, 33.4); site,
      African American race or ethnicity, and male sex were also significant
      independent associations. Children in the overweight (> 85th percentile for body
      mass index) group had significantly higher adjusted means for total blood
      cholesterol, higher apolipoprotein B concentrations, lower mean HDL-cholesterol
      concentrations, and lower performance on the 9-min run than those in other groups
      (< 15th, 15-49th, or 50-85th body mass index percentiles). Similar results were
      found for these factors for those subjects with greater triceps skinfold
      thickness measurements. Groups of children who were overweight and overfat at
      baseline were more likely to be overweight and overfat at follow-up and to have
      more cardiovascular risk factors than their peers.

PMID- 9537607
TI  - Blood pressure and plasma norepinephrine responses to dexfenfluramine in obese
      postmenopausal women.
AB  - Dexfenfluramine has been shown to reduce body weight and lower blood pressure in
      obese individuals. However. it is not clear whether the blood pressure-lowering
      effect is due to dexfenfluramine or to the loss of weight. This project was
      designed to study the effect of a 5-d treatment of dexfenfluramine on blood
      pressure changes in obese postmenopausal women. Twenty women aged 51-60 y matched
      for body mass index [BMI (in kg/m2) of 34.5-50.1] were assigned to either the
      dexfenfluramine group (15 mg orally twice a day for 5 d) or the control group.
      All subjects were instructed about an isoenergetic diet. Twenty-four-hour
      ambulatory blood pressure, plasma catecholamines, glucose, insulin, and lipids
      were measured at the beginning and repeated at the conclusion of the study. On
      day 5 the mean systolic (SBP) and mean diastolic blood pressures (DBP) in the
      dexfenfluramine group were lower than those of the control group (SBP: 114+/-7 mm
      Hg in the dexfenfluramine group compared with 124+/-12 mm Hg in the control
      group, P < 0.05; DBP: 70+/-9 mm Hg in the dexfenfluramine group compared with
      76+/-10 mm Hg in the control group, P < 0.05). The mean plasma norepinephrine
      concentration was lower in the dexfenfluramine group than in the control group
      (1.60+/-0.5 compared with 2.41+/-0.5 nmol/L, respectively, P < 0.05). No
      differences were noted in epinephrine, glucose, insulin. and lipid concentrations
      between the two groups. We showed that a 5-d treatment of dexfenfluramine
      decreases blood pressure and reduces heart rate in obese postmenopausal women.
      Our data suggest that these effects are results of the direct action of
      dexfenfluramine.

PMID- 9537608
TI  - Energy, macronutrient, and food intakes in relation to energy compensation in
      consumers who drink different types of milk.
AB  - To examine whether total fat intake is actually lower in reduced-fat (low-fat and
      skim) milk drinkers and whether reduced-fat-milk drinkers compensate for energy
      intake we compared the intakes of foods, energy, and energy-yielding nutrients in
      reduced-fat-milk drinkers and whole milk drinkers by using the US Department of
      Agriculture's 1989-1991 nationwide food intake database, the Continuing Survey of
      Food Intakes by Individuals. This database represents a national stratified
      sample population of 15 128 individuals. Of the survey population, approximately
      one-third consumed whole milk, one-third consumed low-fat milk, one-tenth
      consumed skim milk, and one-tenth consumed mixed types of milk. The data provided
      the following information: 1) total fat intake of reduced-fat-milk drinkers is
      significantly (P < or = 0.05) lower than that of whole milk drinkers; 2) in
      general, males but not females compensate for energy by increasing their
      carbohydrate intake; 3) reduced-fat-milk drinkers consume more fruit and
      vegetables (P < or = 0.05) and less red meat and sweets (P < or = 0.05) than
      whole milk drinkers; 4) through their reduction in total fat intake, several age
      groups of skim milk drinkers have achieved the US dietary goal for fat intake,
      ie, < or = 30% of energy intake from fat; 5) teenagers compensate for energy
      intake the least of all age groups; and 6) with advancing age, fewer people drink
      milk and fewer drink whole milk. The data indicate significant sex differences in
      energy compensation, that reduced-fat-milk drinkers consume significantly (P < or
      = 0.05) less fat than whole milk drinkers, and that the US dietary goal for fat
      intake may be practically achieved by consuming reduced-fat foods such as skim
      milk and limiting intakes of high-fat foods such as red meat.

PMID- 9537609
TI  - Fruit consumption, fitness, and cardiovascular health in female adolescents: the
      Penn State Young Women's Health Study.
AB  - The objective of this study was to compare the relations among nutrient intake,
      fitness, serum antioxidants, and cardiolipoprotein profiles in female
      adolescents. The study design was a cross-sectional analysis of the Penn State
      Young Women's Health Study. The present study was performed with the entire
      cohort (n = 86) when they were 17.1+/-0.5 y (x+/-SD) of age. Primary measurements
      included cardiolipoprotein indexes, serum antioxidants, nutrient intakes, aerobic
      fitness, and percentage body fat. The cohort was stratified by estimated maximal
      oxygen uptake (VO2max) measurements and by percentage body fat. The fifth
      quintile by estimated VO2max had significantly lower percentage body fat, higher
      athletic scores, higher fruit intake, lower total serum cholesterol, and lower
      ratios of total serum cholesterol to HDL cholesterol than members of the first
      quintile. When the members of the first and fifth quintiles by percentage body
      fat were compared, the first quintile had significantly lower weight, lower body
      mass index, higher estimated VO2max, higher athletic scores, lower ratios of
      total serum cholesterol to HDL cholesterol, and higher fruit, carbohydrate, and
      fiber intakes. Correlation analyses performed with the data for the entire cohort
      showed fruit consumption to be positively correlated with estimated VO2max, and
      predicted VO2max to be positively correlated with circulating beta-carotene and
      alpha-tocopherol. This study provided evidence that the positive associations of
      exercise and fruit consumption with cardiovascular health apply to female
      adolescents as well as to adults.

PMID- 9537610
TI  - Human fatty acid synthesis is reduced after the substitution of dietary starch
      for sugar.
AB  - Using new nonisotopic and isotopic methods, we showed previously that fatty acid
      synthesis was markedly stimulated in weight-stable normal volunteers by a very
      low-fat formula diet with 10% of energy as fat and 75% as short glucose polymers.
      In this study, we determined whether fatty acid synthesis was equally stimulated
      by a very-low-fat solid diet made with foods consumed typically. Four normal
      volunteers consumed the same very-low-fat formula diet for 25 d and then an
      isoenergetic solid food diet with 10% of energy as fat and 75% as starch, simple
      sugars, and fiber for 25 d. To measure fatty acid synthesis, the fatty acid
      compositions of the diets were matched to the composition of each subject's
      adipose tissue and compared with the composition of VLDL-triacylglycerol. In all
      subjects, the large increases in newly formed palmitate and decreases in
      linoleate in VLDL-triacylglycerol were quickly reversed by the solid food diet,
      and the fraction of de novo synthesized fatty acids in fasting VLDL
      triacylglycerol decreased from 30-54% to 0-1%. In a second group of subjects, the
      stimulation of fatty acid synthesis by the formula diet with 75% glucose polymers
      was similarly reduced by a formula diet with amounts of fat, starch, and sugar
      chosen to mimic those of the solid food diet, but persisted after the addition of
      fiber or a diet with 75% sugar. In conclusion, an increase in fatty acid
      synthesis and palmitaterich, linoleate-poor VLDL-triacylglycerol induced by very
      low-fat, high-sugar diets may be reduced by the substitution of dietary starch
      for sugar with potentially beneficial effects on cardiovascular health.

PMID- 9537611
TI  - Twenty-four-hour L-[1-(13)C]tyrosine and L-[3,3-(2)H2]phenylalanine oral tracer
      studies at generous, intermediate, and low phenylalanine intakes to estimate
      aromatic amino acid requirements in adults.
AB  - Daily pattern and rates of whole-body tyrosine oxidation and phenylalanine
      hydroxylation were determined in young adults (15 men, 1 woman) receiving
      [13C]tyrosine and [(2)H2]phenylalanine via primed, constant oral infusion and
      [(2)H4]tyrosine by vein (five subjects also received [(2)H3]leucine
      simultaneously by vein) continuously for 24 h (12 h fast then 12 h fed). Subjects
      were given a diet supplying 96.6 (n = 5), 35.6 (the proposed requirement; n = 5),
      and 18.5 mg phenylalanine x kg(-1) x d(-1) (n = 6) based on an otherwise adequate
      L-amino acid mixture for 6 d before the 24-h tracer study began. [Each diet was
      low in tyrosine: 6.79 mg x kg(-1) x d(-1).] Our hypothesis was that subjects
      would be in tyrosine equilibrium, positive balance, or both, at the 96.6- and
      35.6-mg intakes and in distinctly negative balance at the 18.5-mg intake. The
      diurnal pattern in phenylalanine and tyrosine kinetics was dependent on the
      intake and, presumably, on the adequacy of dietary phenylalanine. Wholebody
      tyrosine balances, determined from rates of phenylalanine hydroxylation and
      tyrosine input and oxidation were negative (0.05 < P < 0.1 from zero balance)
      with the low (18.5 mg) phenylalanine intake [total aromatic amino acid (AAA)
      intake: 25.3 mg x kg(-1) x d(-1)] but at equilibrium (P > 0.05 from zero balance)
      with the two higher phenylalanine intakes. Whole-body AAA balance (AAA intake -
      tyrosine oxidation) was negative (P < 0.05 from zero balance) with the low
      intake, at equilibrium with the intermediate intake, and apparently distinctly
      positive (P < 0.05) with the generous intake. Despite model limitations, as
      discussed, these findings lend further support for a proposed, tentative value
      for a total mean requirement of 39 mg AAA x kg(-1) x d(-1).

PMID- 9537612
TI  - An oral glutamine load enhances renal acid secretion and function.
AB  - In a recent study, a small oral glutamine load acutely elevated plasma
      bicarbonate concentrations in healthy adults (Am J Nutr 1995;61:1058-61). The
      present study was designed to elucidate the renal mechanism underlying the base
      generating response to L-glutamine. Accordingly, vehicle (489 mL diet soda) or
      vehicle plus 2 g L-glutamine (28 mg/kg body wt) was ingested and the gain in
      extracellular fluid volume bicarbonate was compared with renal acid elimination
      as either ammonium excretion or tubular acid secretion (titratable acid plus
      bicarbonate reabsorption). Vehicle alone, which contained 27 mmol acid, did not
      increase extracellular fluid volume bicarbonate over the 90-min period. In
      contrast, L-glutamine increased plasma bicarbonate concentration (from 25.4+/-2
      to 27.9+/-1 mmol/L, P < 0.05) and extracellular fluid volume bicarbonate by an
      estimated 39+/-10 mmol. When added to that required to neutralize the ingested
      acid, the combined total for new bicarbonate generated gave an estimated 66+/-10
      mmol. Surprisingly, ammonium excretion accounted for < 2% of this newly generated
      bicarbonate. However, acid secreted and excreted as net acid (5.2+/-4.0 mmol/90
      min) as well as that coupled to enhanced bicarbonate reabsorption (76+/-20
      mmol/90 min) readily accounted for the estimated base gain (81+/-24 compared with
      66+/-10 mmol/90 min). Concomitant with enhanced renal acid secretion, the oral
      glutamine load elicited an increase in glomerular filtration rate. These results
      rule out a role for L-glutamine as a direct precursor of bicarbonate and instead
      point to an indirect role in accelerating acid secretion, apparently coupled to
      increased glomerular filtration rate.

PMID- 9537613
TI  - Bioavailability of iron glycine as a fortificant in infant foods.
AB  - The bioavailability of iron glycine added to a vegetable infant weaning food was
      compared with ferrous sulfate. Stable, isotopically labeled compounds (57Fe or
      58Fe) were mixed into the midday meal (1.4 mg added Fe/serving) and fed to 9-mo
      old infants on alternate days for 8 d. Bioavailability, expressed as a percentage
      of the dose consumed, was measured from isotopic enrichment of hemoglobin 14 d
      after the last test meal. There was no difference between iron glycine and
      ferrous sulfate (x+/-SEM): 9.0+/-0.7% and 9.9+/-0.8%, respectively. The effect of
      chelation was examined by measuring iron bioavailability of iron glycine and
      ferrous sulfate added to a high-phytate (310 mg/100 g) whole-grain cereal weaning
      food and comparing it with a lower-phytate (147 mg/100 g) vegetable food, as used
      in the first study. Both iron compounds had lower bioavailability from the high
      phytate food, 5.2+/-0.5% for iron glycine and 3.8+/-0.9% for ferrous sulfate,
      than the lower-phytate food, 9.8+/-1.5% for iron glycine and 9.1+/-1.3% for
      ferrous sulfate. The results showed no significant difference in bioavailability
      between the two forms of iron when added to infant weaning foods, suggesting that
      the glycine complex was fully or partially dissociated in the gastrointestinal
      tract. It is concluded that chelation does not improve the bioavailability of
      iron in the presence of dietary inhibitors.

PMID- 9537614
TI  - Human plasma and tissue alpha-tocopherol concentrations in response to
      supplementation with deuterated natural and synthetic vitamin E.
AB  - We report a comparison of natural and synthetic vitamin E in humans using
      deuterium labeling to permit the two forms of vitamin E to be measured
      independently in plasma and tissues of each subject. Differences in natural and
      synthetic vitamin E concentrations were measured directly under equal dosage
      conditions using an equimolar mixture of deuterated RRR-alpha-tocopheryl acetate
      and all-rac-alpha-tocopheryl acetate. Two groups of five adults took 30 mg of the
      mixture as a single dose and as eight consecutive daily doses, respectively.
      After a 1-mo interval the schedule was repeated but with a 10-fold higher dose
      (ie, 300 mg). In each case, the ratio of plasma d3-RRR-alpha-tocopherol to d6-all
      rac-alpha-tocopherol (RRR:rac) increased from approximately 1.5-1.8 to
      approximately 2 after dosing ended. In an elective surgery study in which 22
      patients were given 150 mg/d for up to 41 d before surgery, the RRR:rac in
      tissues was lower than in plasma and the percentage of deuterated alpha
      tocopherol was lower in all tissues except gallbladder and liver. In a terminally
      ill patient given 30 mg/d for 361 d, plasma and tissue (x+/-SD) RRR-rac ratios
      (and % deuterated alpha-tocopherol) at autopsy were 2.06 (6.3%) and 1.71+/-0.24
      (5.9+/-2.2%), respectively. In a second terminally ill patient given 300 mg/d for
      615 d, the corresponding values were 2.11 (68%) and 2.01+/-0.17 (65+/-10%),
      respectively. The results indicated that natural vitamin E has roughly twice the
      availability of synthetic vitamin E. This 2:1 ratio is significantly higher than
      the currently accepted RRR:rac of 1.36:1.00. Gamma-Tocopherol, expressed as a
      fraction of total unlabeled tocopherols in 15 elective surgery patients, was 1.4
      4.6 (mean: 2.6) times greater in adipose tissue, muscle, skin, and vein than in
      plasma, which is a substantially larger fraction than had been recognized
      previously.

PMID- 9537615
TI  - Bone changes after 3 mo of lactation: influence of calcium intake, breast-milk
      output, and vitamin D-receptor genotype.
AB  - Factors influencing the change in bone mineral after 3 mo of lactation were
      investigated in 47 breast-feeding mothers, 11 formula-feeding mothers, and 22
      nonpregnant, nonlactating control subjects. At 6-8 wk postpartum, the breast
      feeding group had a mean (+/-SD) calcium intake of 34.8+/-13.2 mmol/d and breast
      milk volume, calcium concentration, and calcium output of 0.865+/-0.230 L/d,
      7.41+/-1.25 mmol/L, and 6.41+/-2.00 mmol/d, respectively. There was no relation
      between calcium intake and any breast-milk variable. Dual-energy X-ray
      absorptiometry of the whole body, spine, hip, and forearm was performed at 0.5
      and 3 mo. There were significant decreases in bone mineral content at the spine
      (3.96%; 95% CI: 4.86%, 3.06%), femoral neck (2.39%; 95% CI: 3.61%, 1.17%), total
      hip (1.51%; 95% CI: 2.45%, 0.60%), and whole body (0.86%; 95% CI: 1.29%, 0.43%)
      in breast-feeding mothers but not in formula-feeding mothers or nonpregnant,
      nonlactating women. These changes were not related to calcium intake, breast-milk
      calcium concentration, vitamin D-receptor genotype, postpartum weight change, or
      use of the progesterone-only contraceptive pill. After adjustment for bone area,
      breast-milk volume and height were identified as significant predictors at the
      spine, such that greater decreases were associated with taller mothers (P =
      0.007) and those with greater breast-milk volume (P = 0.001). This finding
      suggests that the marked bone mineral changes observed in breast-feeding mothers
      represented a physiologic response to lactation that was independent of dietary
      calcium supply.

PMID- 9537616
TI  - A longitudinal study of calcium homeostasis during human pregnancy and lactation
      and after resumption of menses.
AB  - To clarify the role of the intestine, kidney, and bone in maintaining calcium
      homeostasis during pregnancy and lactation and after the resumption of menses, a
      longitudinal comparison was undertaken of 14 well-nourished women consuming
      approximately 1200 mg Ca/d. Measurements were made before conception
      (prepregnancy), once during each trimester of pregnancy (T1, T2, and T3), early
      in lactation at 2 mo postpartum (EL), and 5 mo after resumption of menses.
      Intestinal calcium absorption was determined from the enrichment of the first 24
      h urine sample collected after administration of stable calcium isotopes. Bone
      mineral of the total body and lumbar spine was measured by dual-energy X-ray
      absorptiometry and quantitative computerized tomography, respectively. Twenty
      four-hour urine and fasting serum samples were analyzed for calcium, calcitropic
      hormones, and biochemical markers of bone turnover. Despite an increase in
      calcium intake during pregnancy, true percentage absorption of calcium increased
      from 32.9+/-9.1% at prepregnancy to 49.9+/-10.2% at T2 and 53.8+/-11.3% at T3 (P
      < 0.001). Urinary calcium increased from 4.32+/-2.20 mmol/d at prepregnancy to
      6.21+/-3.72 mmol/d at T3 (P < 0.001), but only minor changes in maternal bone
      mineral were detected. At EL, dietary calcium and calcium absorption were not
      significantly different from that at prepregnancy, but urinary calcium decreased
      to 1.87+/-1.22 mmol/d (P < 0.001) and trabecular bone mineral density of the
      spine decreased to 147.7+/-21.2 mg/cm3 from 162.9+/-25.0 mg/cm3 at prepregnancy
      (P < 0.001). Calcium absorption postmenses increased nonsignificantly to 36.0+/
      8.1% whereas urinary calcium decreased to 2.72+/-1.52 mmol/d (P < 0.001). We
      concluded that fetal calcium demand was met by increased maternal intestinal
      absorption; early breast-milk calcium was provided by maternal renal calcium
      conservation and loss of spinal trabecular bone, a loss that was recovered
      postmenses.

PMID- 9537617
TI  - Suboptimal zinc status in pregnant Malawian women: its association with low
      intakes of poorly available zinc, frequent reproductive cycling, and malaria.
AB  - A study of 152 rural Malawian women aged 23.2+/-5.5 y (x+/-SD) at 24 wk gestation
      included measurements of biochemical indexes of zinc (plasma and hair), protein
      (serum albumin), and infection (serum C-reactive protein, white blood cell count,
      and malaria), and dietary intakes (via three interactive 24-h dietary recalls).
      Data on health, demographic and socioeconomic status, family characteristics,
      reproductive history, and anthropometry were also collected. The study revealed a
      high prevalence of suboptimal zinc status: 36% of the women had low plasma and
      46% had low hair zinc values. Median daily intake of zinc (9.0 mg) was low and
      poorly available: 61% was provided by cereals and 20% by flesh foods. Median
      intake of animal protein was only 5.6 g/d, and phytate intakes were high (1.4
      g/d). Women consuming diets with phytate-zinc ratios > 17 (the median) had lower
      hair zinc concentrations (1.6 compared with 1.8 micromol/g, P < 0.03), were older
      (24 compared with 20 y, P < 0.02), and had a higher number of pregnancies (3
      compared with 2, P < 0.02) than those consuming diets with a phytate-zinc ratio <
      17. Frequent reproductive cycling was related to zinc status; hair zinc was
      higher for a prima- than for a multigravida (2.0 compared with 1.6 micromol/g, P
      < 0.01). Malaria prevalence was also associated with hair zinc (P < 0.05) but not
      with plasma zinc, after the number of pregnancies was controlled for. We conclude
      that low intakes of poorly available dietary zinc, frequent reproductive cycling,
      and malaria prevalence are three major factors in the etiology of suboptimal zinc
      status in these rural, pregnant Malawian women.

PMID- 9537618
TI  - Role of irritable bowel syndrome in subjective lactose intolerance.
AB  - It has been suggested that the symptoms of irritable bowel syndrome (IBS) may be
      wrongly attributed to lactose intolerance. We examined the relations among IBS,
      demographic factors, living habits, and lactose intolerance. On the basis of a
      lactose tolerance test with ethanol, 101 of the 427 healthy subjects studied were
      lactose maldigesters and 326 were lactose digesters. IBS was diagnosed by means
      of the Bowel Disease Questionnaire, according to the Rome criteria. The use of
      dairy products and symptoms experienced after their consumption were recorded.
      IBS was found in 15% of both the lactose maldigesters and lactose digesters. One
      third of the subjects reported intolerance to dairy products containing < or = 20
      g lactose. About half of this third were lactose maldigesters and about half were
      lactose digesters. As explanations for this subjective lactose intolerance, the
      logistic regression model estimated lactose maldigestion (odds ratio: 10.3; 95%
      CI: 5.2, 20.4), IBS (4.6; 2.1, 10.1), experience of symptoms other than
      gastrointestinal ones (2.3; 1.2, 4.5), and female sex (2.1; 1.1, 4.0).
      Characteristics common to both subjective lactose intolerance and IBS were female
      sex and the experience of abdominal pain in childhood (P < 0.01). Age, regularity
      of meals, and the amount of physical activity were not associated with either
      subjective lactose intolerance or IBS. Of the subjects with IBS, the percentage
      of lactose maldigesters was the same as in the whole study group (24%) but the
      number who reported lactose intolerance was higher (60% compared with 27%, P <
      0.001). We showed a strong relation among subjective lactose intolerance, IBS,
      the experience of abdominal pain in childhood, and female sex.

PMID- 9537619
TI  - Bioavailability of phylloquinone from an intravenous lipid emulsion.
AB  - This randomized, controlled study evaluated the bioavailability of phylloquinone
      from an intravenous lipid emulsion. A mild vitamin K deficiency was induced in 12
      healthy adult men and women by dietary restriction of phylloquinone (40 microg/d,
      days 1-11) and by administration of warfarin (1.0 mg/d, days 5-11). On day 11,
      subjects received a 500-mL intravenous solution of either lipid or saline, both
      of which contained 154 microg phylloquinone. Bioavailability was assessed by
      serial measurements of plasma phylloquinone, vitamin K1-2,3-epoxide. PIVKA-II
      (proteins induced by vitamin K absence or antagonists-II), and percentage
      undercarboxylated osteocalcin. As a result of vitamin K deficiency and minidose
      warfarin, vitamin K1-2,3-epoxide, PIVKA-II, and percentage undercarboxylated
      osteocalcin increased significantly between days 1 and 11 (P = 0.05, 0.016, and
      0.001, respectively). With the infusions, plasma phylloquinone increased in both
      groups (P = 0.001). After the infusions vitamin K,-2,3-epoxide decreased in both
      groups (P = 0.002). Changes in plasma phylloquinone and vitamin K1-2,3-epoxide
      were no different in the two groups (mean areas under the curves +/- SEM: 116+/
      13 nmol x h/L for the saline group and 102+/-20 nmol x h/L for the lipid group
      for phylloquinone; 38.6+/-7.5 nmol x h/L for the saline group and 31.3+/-9.0 nmol
      x h/L for the lipid group for vitamin K1-2,3-epoxide). PIVKA-II decreased
      significantly from baseline values (P = 0.005) in both groups after the
      infusions. Intravenous lipid reversed the effects of minidose warfarin and of
      dietary restriction of phylloquinone on hemostasis and vitamin K nutritional
      status. This reversal was no different from that seen with the infusion of
      phylloquinone in a saline solution.

PMID- 9537620
TI  - Dietary determinants of iron stores in a free-living elderly population: The
      Framingham Heart Study.
AB  - Epidemiologic studies have found a relation between body iron stores and risk of
      chronic disease. Iron-absorption studies from single meals have shown that many
      dietary factors can influence nonheme-iron bioavailability. However, little is
      known about the association of these dietary factors with iron stores in free
      living elderly populations. To address this question, we investigated the
      consumption of various dietary components and iron stores in an elderly sample of
      The Framingham Heart Study participants. Serum ferritin was used as a measure of
      body iron stores in 634 free-living elderly (67-93 y of age), and dietary intake
      during the previous year was assessed by a food-frequency questionnaire. The
      relation between serum ferritin and various dietary factors was assessed by
      multiple regression analysis. Subjects whose ferritin concentrations might be
      pathologically elevated because of infection, inflammation, liver disease, or
      genetic hemochromatosis were excluded from the analysis. After we controlled for
      sex, age, body mass index, total energy intake, smoking, and use of aspirin and
      other medications known to affect blood loss, we found five significant dietary
      factors associated with iron stores. Heme iron, supplemental iron, dietary
      vitamin C, and alcohol were positively associated with serum ferritin, whereas
      coffee intake had a negative association. As expected, sex was a strong predictor
      of serum ferritin-women having significantly lower mean concentrations than men.
      However, age was not related to serum ferritin in our elderly population. Our
      results suggest that in typical Western-style diets, a small number of dietary
      factors probably modulate the bioavailability of dietary iron and influence the
      accumulation of iron stores.

PMID- 9537621
TI  - Effect of weight loss on bone mineral content and bone mineral density in obese
      women.
AB  - Studies of body-composition changes during weight loss have had conflicting
      results with regard to changes in bone mineral content (BMC) and bone mineral
      density (BMD). We examined BMC and BMD for changes during weight loss. Fourteen
      women enrolled in a 15-wk weight loss program. Dual-energy X-ray absorptiometry
      (DXA) measures of the total body were made at baseline (T1), the midpoint of
      weight loss (T2), and at the end of weight loss (T3). Body weight changed
      significantly throughout the 15 wk, declining from a high of 89.7+/-3.6 to 74.1+/
      3.2 kg. Fat-free mass declined initially (47.8+/-1.7 kg at T1, 45.7+/-1.4 kg at
      T2, and 46.0+/-1.5 kg at T3) and then stabilized. Fat mass changed significantly
      during the study (39.2 kg at T1, 32.4 kg at T2, and 29.3 kg at T3). No
      significant differences were observed in BMC or bone areal measurement during the
      study. However, BMD declined significantly from baseline (1.217 g/cm2 at T1,
      1.197 g/cm2 at T2, and 1.200 g/cm2 at T3). The changes in BMC and BA were in
      opposite directions, resulting in a significant decline in BMD without a loss of
      BMC. These data suggest that changes in BMD observed with weight loss may be the
      result of a lack of instrument sensitivity when body weight and composition
      change and are simply an artifact and not a physiologic change in BMD. Further
      research is needed to determine the full effect of weight loss on BMC, bone area,
      and BMD.

PMID- 9537622
TI  - The elderly need oral vitamin B-12.

PMID- 9537623
TI  - Differences in resting metabolic rate between obese black and white women.

PMID- 9537624
TI  - Trends in breakfast consumption for children in the United States from 1965-1991.
AB  - We examined breakfast consumption patterns and trends between 1965 and 1991 for
      children (1-10 y old) and adolescents (11-18 y old) in the United States. The
      analysis was undertaken by pooling nationally representative samples obtained
      from the Nationwide Food Consumption Surveys of 1965 and 1977-1978 and the 1989
      1991 Continuing Survey of Food Intakes by Individuals. Breakfast consumption,
      defined as the consumption of food, beverage, or both between 0500 and 1000, was
      the focus of the trends analysis. Descriptive results indicated a decline in
      breakfast consumption between 1965 and 1991, particularly for older adolescents
      aged 15-18 y; the rates for boys and girls declined from 89.7% and 84.4%,
      respectively, in 1965 to 74.9% and 64.7%, respectively, in 1991. Multivariate
      results indicated that breakfast consumption declined predominantly because of
      behavioral changes and not the population's changing sociodemographic patterns.
      The nutritional quality of foods consumed at breakfast has improved since 1965,
      with significant shifts toward consumption of lower-fat milk and smaller changes
      in other food groups. The improvement over time in the quality of food consumed
      at breakfast, however, is offset by the large percentage of persons aged > or =
      11 y who do not presently consume breakfast. Given the association of obesity
      with less frequent breakfast consumption and the rise in obesity among persons of
      this age group, a renewed emphasis on the importance of breakfast is warranted.

PMID- 9537625
TI  - Nutrient contribution of breakfast, secular trends, and the role of ready-to-eat
      cereals: a review of data from the Bogalusa Heart Study.
AB  - Breakfast consumption has been identified as an important factor in the
      nutritional well-being of children. Several studies have indicated that omission
      of breakfast or consumption of an inadequate breakfast is a factor contributing
      to poor school performance and to dietary inadequacies that are rarely
      compensated for in other meals of the day. Differences have also been observed in
      the nutrient density of the breakfast meal, depending on whether it was consumed
      at school or at home. Ready-to-eat cereals make a significant contribution to the
      nutritional quality of diets of children and young adults. The Bogalusa Heart
      Study, which began 25 y ago, is an epidemiologic investigation of cardiovascular
      risk factors and environmental determinants in a biracial pediatric population.
      The purpose of this review is to present data from the Bogalusa Heart Study and
      other studies supporting the statements above.

PMID- 9537626
TI  - Glucose, memory, and aging.
AB  - Circulating glucose concentrations regulate many brain functions, including
      learning and memory. Much of the evidence for this view comes from experiments
      assessing stress-related release of epinephrine with subsequent increases in
      blood glucose concentrations. One application of this work has been to
      investigate whether age-related memory impairments result from dysfunctions in
      the neuroendocrine regulation of the brain processes responsible for memory. Like
      humans, aged rodents exhibit some memory impairments that can be reversed by
      administration of epinephrine or glucose. In elderly humans, ingestion of glucose
      enhances some cognitive functions, with effects best documented thus far on tests
      of verbal contextual and noncontextual information. Glucose also effectively
      enhances cognition in persons with Alzheimer disease or Down syndrome. Although
      earlier evidence suggested that glucose does not enhance cognitive function in
      healthy young adults, more recent findings suggest that glucose is effective in
      this population, provided the tests are sufficiently difficult. In college
      students, glucose consumption significantly enhanced memory of material in a
      paragraph. Glucose also appeared to enhance attentional processes in these
      students. Neither face and word recognition nor working memory was influenced by
      treatment with glucose. The neurobiological mechanisms by which glucose acts are
      under current investigation. Initial evidence suggests that glucose or a
      metabolite may activate release of the neurotransmitter acetylcholine in rats
      when they are engaged in learning. Consequently, the issue of nutrition and
      cognition becomes increasingly important in light of evidence that circulating
      glucose concentrations have substantial effects on brain and cognitive functions.

PMID- 9537627
TI  - Breakfast, blood glucose, and cognition.
AB  - This article compares the findings of three studies that explored the role of
      increased blood glucose in improving memory function for subjects who ate
      breakfast. An initial improvement in memory function for these subjects was found
      to correlate with blood glucose concentrations. In subsequent studies, morning
      fasting was found to adversely affect the ability to recall a word list and a
      story read aloud, as well as recall items while counting backwards. Failure to
      eat breakfast did not affect performance on an intelligence test. It was
      concluded that breakfast consumption preferentially influences tasks requiring
      aspects of memory. In the case of both word list recall and memory while counting
      backwards, the decline in performance associated with not eating breakfast was
      reversed by the consumption of a glucose-supplemented drink. Although a morning
      fast also affected the ability to recall a story read aloud, the glucose drink
      did not reverse this decline. It appears that breakfast consumption influences
      cognition via several mechanisms, including an increase in blood glucose.

PMID- 9537628
TI  - Fasting and cognition in well- and undernourished schoolchildren: a review of
      three experimental studies.
AB  - This paper reviews three experiments on the effects of an overnight and morning
      fast on attention and memory processes among 9-11-y-old children. Two of the
      experiments focused on middle-class, well-nourished boys and girls in the United
      States: the third involved boys from low-income families with and without
      nutritional risk in Huaraz, Peru. All experiments used the same crossover design
      and followed similar experimental procedures to control the subjects' intakes and
      motor activity during the study period. The children were admitted to a research
      center on two different evenings, approximately 7 d apart. After arrival the
      children ate dinner, played table games or watched television, and went to bed.
      They were awakened at 0730 and, by design, were either served breakfast
      (approximately 2301 kJ) or not. At 1100 they took psychologic tests that assessed
      recall from working memory and competence in discriminating visual stimuli. At
      1200 the children were discharged. The consequences of the overnight and morning
      fast, particularly among the children who were nutritionally at risk, included
      slower stimulus discrimination, increased errors, and slower memory recall. We
      propose that these alterations result from a state of metabolic stress in which
      homeostatic mechanisms work to maintain circulating glucose concentrations.

PMID- 9537629
TI  - Evaluation of school feeding programs: some Jamaican examples.
AB  - It is hypothesized that giving children a daily breakfast at school may improve
      their scholastic achievement through several mechanisms: increasing the time
      spent in school, improving certain cognitive functions and attention to tasks,
      and, perhaps indirectly, improving nutritional status. Two Jamaican studies
      showed that providing breakfast to students at school improved some cognitive
      functions, particularly in undernourished children. However, changes in classroom
      behavior varied depending on the quality of the school. Children in better
      organized schools concentrated on tasks for longer periods and made fewer
      undesirable movements, whereas in poorly organized schools the children's
      behavior deteriorated. Studies to date have provided insufficient evidence to
      determine whether children's long-term scholastic achievement is improved by
      eating breakfast daily. Well-designed, randomized, controlled, long-term trials
      are essential for determining public policy on the implementation of school
      feeding programs.

PMID- 9537630
TI  - School feeding in Jamaica: a review of its evaluation.
AB  - This paper reviews two studies that evaluated the school feeding program in
      Jamaica. The first examined 115 children aged 12-13 y who were enrolled in three
      classes in a poor, rural school. One class was served the standard school meal at
      0900 whereas the other two classes served as controls. The outcome variables
      included school achievement, attendance, and weight gain. After one semester, the
      class receiving the meal showed improved arithmetic scores and school attendance
      compared with the control classes; however, they showed no weight gain. The
      academic improvement remained significant after school attendance was controlled
      for. It was therefore hypothesized that the gains in arithmetic resulted from the
      alleviation of hunger in the classroom. The other study, conducted in a metabolic
      ward, examined the effects of missing breakfast on cognitive function in 90
      children aged 9-10 y and of differing nutritional status. Using a crossover
      design, the investigators tested each child on two mornings 1 wk apart, once
      after serving them breakfast and second without. Breakfast, consisting of the
      school program meal, was served at 0800. When severely malnourished, stunted, or
      wasted children received no breakfast, their performance in various cognitive
      tests deteriorated. These results indicate that alleviation of hunger was one of
      the mechanisms by which school feeding improved academic achievement in the
      previous study. Undernourished children are more likely to benefit from school
      feeding programs than are adequately nourished children.

PMID- 9537631
TI  - When science and politics listen to each other: good prospects from a new school
      breakfast program in Peru.
AB  - This article provides an overview of a school breakfast program implemented in
      1993 in the Peruvian Andes. The program, designed by the Instituto de
      Investigacion Nutricional in Lima and supported by the government of Peru,
      constitutes a clear departure from previous school feeding programs, which were
      heavily politicized and poorly documented. From the program's inception,
      nutritionists, managers, and social scientists have collaborated to produce a
      sound nutritional design, efficient distribution mechanisms, and effective
      evaluation methods. During the program's first year, controlled evaluations
      conducted in several Andean regions documented improved dietary intake and a
      significant decline in the prevalence of anemia. An educational evaluation also
      found improved verbal skills, higher school attendance, and lower dropout rates
      among recipients of the school breakfast. The results have prompted the Peruvian
      government to continue supporting the program, thus setting a new standard for
      the effective management of social expenditure in the context of economic
      adjustment.

PMID- 9537632
TI  - US Department of Agriculture School Breakfast Program.
AB  - This article reviews the history of the US Department of Agriculture School
      Breakfast Program (SBP) and provides a synthesis of factors influencing
      participation rates. Certain children are more likely to participate than others,
      such as those in lower grades and those from low-income households, and African
      American, Hispanic, and male students. A few studies in the past 25 y have
      examined the effectiveness of the SBP in improving the diets and nutritional
      status of children. The overall pattern that emerges from these studies is that
      the SBP contributes to improved nutrient intake in program participants. Less
      attention has been devoted to assessing the effects of SBP on cognitive
      development. Some of the evidence reviewed here suggests that the SBP
      significantly improves school performance and reduces absenteeism and tardiness.
      Future directions for research and operation of the SBP are discussed in light of
      the changing dietary profile of American children.

PMID- 9537633
TI  - Breakfast and cognition: an integrative summary.
AB  - In this supplement, the papers presented at the International Symposium on
      Breakfast and Performance in Napa, CA in 1995 are summarized and integrated with
      data published since that time. In particular, the focus is on issues of research
      design, measurements, mechanisms, potential effect modifiers (eg, age), and
      relevance for public policy. No definitive conclusions can be drawn from the
      existing data on either the long- and short-term benefits of breakfast on
      cognition and school learning or the mechanisms that mediate this relation. The
      pooled data suggest that omitting breakfast interferes with cognition and
      learning, an effect that is more pronounced in nutritionally at-risk children
      than in well-nourished children. At the very least, breakfast consumption
      improves school attendance and enhances the quality of the students' diets.

PMID- 9537634
TI  - Does examination of urinary sediment identify individuals with Gulf War syndrome?
      A pilot study.
AB  - BACKGROUND: Many veterans who were involved in the Persian Gulf theater of
      operations have had a variety of unexplained physical complaints, collectively
      called the Gulf War syndrome or similar names. There has been much debate on the
      issue and numerous publications, both in the medical and the lay press. A method
      for examining urinary sediment that was developed in an effort to identify
      nonculturable bacteria has been used in Gulf War veterans and was the basis for
      intensive antimicrobial therapy in many of them. METHODS: We evaluated eight Gulf
      War veterans with complaints compatible with Gulf War syndrome. Subjects were
      from various parts of the United States. A detailed history and physical
      examination were performed. Urine was obtained before and after prostatic massage
      (men) or before and after pelvic examinations (women) and was tested by a
      previously described microscopic method as well as by culture and conventional
      Gram stain. Age- and sex-matched healthy control subjects were tested similarly
      and concurrently. RESULTS: Two female Gulf War veterans had findings of Candida
      albicans and Klebsiella pneumoniae by conventional culture. The same organism
      types were seen both by the special method and by conventional Gram stain. All
      other subjects and controls were completely indistinguishable. CONCLUSION:
      Examining the urinary sediment by this elaborate method does not differentiate
      persons with Gulf War syndrome from normal, healthy control subjects who were
      never in the Persian Gulf area.

PMID- 9537635
TI  - Vitamin E and coenzyme Q concentrations in the thyroid tissues of patients with
      various thyroid disorders.
AB  - To clarify the different roles of free radical scavenging systems in various
      thyroid disorders, we measured the levels of alpha-, beta-, and gamma-tocopherols
      and coenzyme Q in the thyroid tissues of patients with thyroid tumors and Graves'
      disease using high-performance liquid chromatography. The levels of alpha
      tocopherols and gamma-tocopherols in the thyroid tissue of patients with
      papillary carcinoma and the level of gamma-tocopherol in the thyroid tissue of
      patients with malignant lymphoma were elevated compared with those in normal
      thyroid tissues. The level of coenzyme Q was reduced in the thyroid tissue of
      patients with Graves' disease and follicular and papillary thyroid carcinomas.
      These findings imply that vitamin E and coenzyme Q as scavengers play some role
      in thyroid follicular cell hyperfunction or dysfunction.

PMID- 9537636
TI  - The prevalence and significance of leukocytosis in upper gastrointestinal
      bleeding.
AB  - Although leukocytosis has long been recognized to occur in patients with
      hemorrhage, there are no data regarding leukocytosis in patients with upper
      gastrointestinal bleeding. We evaluated the prevalence and significance of the
      admission white blood cell count in consecutive patients admitted to Grady
      Memorial Hospital with upper gastrointestinal bleeding seen prospectively over a
      50-month period. Any white count greater than 8.5 x 10(3)/mm3 was considered
      abnormal. Of the 731 patients eligible for the study, leukocytosis was seen in
      463 (63%). When compared to patients with a normal white count, patients with
      leukocytosis on admission were more likely to be tachycardic (31.4% versus 24.3%,
      P = 0.04) and hypotensive (10.9% versus 5.7%, P = 0.018), required more units of
      blood (4.6+/-5.9 versus 3.5+/-6.0, P = 0.01), had a longer hospital stay (7.3+/
      9.7 versus 5.9+/-6.2 days, P = 0.01), and required more frequent surgical
      intervention for bleeding (8.0% versus 4.2%, P = 0.04). No significant difference
      in mortality was seen between patients with leukocytosis and those with a normal
      white count (8.7% versus 6.4%, P = 0.27). Leukocytosis is common in patients with
      upper gastrointestinal bleeding, appears to reflect the severity of the bleeding
      episode, and is associated with a more complicated course.

PMID- 9537637
TI  - Role of human leukocyte interferon-alpha in the treatment of patients with
      polycythemia vera.
AB  - Eighteen patients with polycythemia vera who were less than 60 years old received
      human leukocyte interferon-alpha subcutaneously at a starting dose of 3 MU three
      times a week. The interferon dose was escalated to 6 MU three times a week if it
      was well tolerated and disease was not controlled after 3 months of treatment at
      the lower dose. Hematologic response was defined as complete if the hematocrit
      was maintained at less than 45% in the absence of phlebotomy and partial if the
      hematocrit was kept at 45% to 50%, associated with a 50% or greater reduction of
      phlebotomy requirements; no response was defined as a response less than a
      partial response. Complete disease control was achieved in 11 patients, with
      partial control in a further six cases. One patient failed to respond. Median
      duration of response was 16 months (range 5 to 43 months), with 15 patients still
      under treatment. Therapy with human leukocyte interferon-alpha significantly
      improved (p <.01) phlebotomy requirements, the degree of splenomegaly, pruritus
      scores, iron stores and mean red cell volume values, and platelet and leukocyte
      counts. Interferon treatment did not produce remarkable side effects and no
      patient withdrew from the study because of intolerance. We conclude that
      subcutaneous human leukocyte interferon-alpha is an effective and well-tolerated
      therapy in the management of polycythemia vera-associated myeloproliferation and
      pruritus in patients less than 60 years old.

PMID- 9537639
TI  - Temporary epicardial atrial pacing electrodes: duration of effectiveness based on
      position.
AB  - BACKGROUND: To investigate the duration of effectiveness in the postoperative
      period of temporary epicardial atrial pacing electrodes on the right atrium,
      based on position. METHODS: The function of temporary epicardial atrial pacing
      electrodes were examined in 55 patients undergoing coronary artery bypass
      grafting from March 20, 1996, to July 31, 1996, at Allegheny University
      Hospitals, Hahnemann Division, Philadelphia, PA. There were 41 male and 14 female
      patients. The mean age was 71 years (range 35 to 86 years). Two atrial and two
      ventricular temporary epicardial pacing electrodes were placed at the termination
      of cardiopulmonary bypass. One atrial electrode was placed on the body of the
      right atrium at the junction of the superior vena cava (body electrode); the
      other was passed through the pursestring of the atrial cannulation site
      (appendage electrode). RESULTS: The mean thresholds for the atrial body
      electrodes on the operative day and postoperative days 1 and 2 were 4.96, 6.67,
      and 6.80 mA, respectively. The mean thresholds for the atrial appendage
      electrodes were 5.98, 7.50, and 8.59 mA, respectively. CONCLUSIONS: Temporary
      epicardial atrial pacing electrodes are more effective when the wires are placed
      in the atrial body of the right atrium than if they are wrapped within the
      pursestring of the right atrial appendage. As a result of these findings, the
      common practice of placing the pacing wire through pursestring tissue should be
      abandoned.

PMID- 9537638
TI  - Probucol improves endothelial-dependent relaxation and decreases vascular
      superoxide production in cholesterol-fed rabbits.
AB  - Recent data indicate that hypercholesterolemia increases endothelial superoxide
      anion (.O2-) production, and that this diminishes the bioactivity of nitric oxide
      produced in the endothelium. Probucol, a drug commonly employed for treatment of
      hypercholesterolemia, has antioxidant properties and inhibits oxidation of low
      density lipoproteins in vitro. We tested the hypothesis that probucol would
      decrease vascular .O2- production and improve endothelium-dependent relaxations
      in cholesterol-fed rabbits. Rabbits were divided into four groups: 1) a control
      group fed a standard diet; 2) a probucol group fed a standard diet containing
      0.3% probucol; 3) a hypercholesterolemic group fed a diet containing 0.5%
      cholesterol; 4) a hypercholesterolemia-probucol group fed a diet containing 0.5%
      cholesterol and 0.3% probucol. The cholesterol-rich diet markedly increased
      plasma total cholesterol level and lipid peroxidation in the plasma, as reflected
      by thiobarbituric acid-reactive substances (TBARS). This concentration of
      probucol did not lower plasma cholesterol, but markedly reduced TBARS in the
      plasma of cholesterol-fed rabbits. Aortic segments from cholesterol-fed rabbits
      produced 1.8-fold more .O2- (assessed by lucigenin-enhanced chemiluminescence)
      and decreased endothelium-dependent vascular relaxations to acetylcholine
      compared to vessels from normal rabbits. In cholesterol-fed rabbits, probucol
      treatment normalized both .O2- production and endothelium-dependent relaxations
      to acetylcholine. In control rabbits, probucol had no effect on either of these
      parameters. We conclude that probucol treatment may prevent .O2(-)-induced
      inactivation of endothelium-derived nitric oxide and reduce vascular oxidant
      stress via reducing the level of .O2-.

PMID- 9537640
TI  - Blood macrophage colony-stimulating factor and thrombin-antithrombin III complex
      concentrations in pregnancy and preeclampsia.
AB  - Macrophage colony-stimulating factor (M-CSF) is a characteristic cytokine that
      plays an essential role in placenta maintenance, and thrombin-antithrombin III
      complex (TAT) is a hemostatic marker that is remarkably altered both in normal
      pregnancy and in preeclampsia. The present study was designed in order to show
      various levels of M-CSF and TAT in pregnancies. Peripheral blood was collected
      from 49 subjects, of whom 31 were normal pregnant women consisting of the four
      groups (namely 10th, 20th, 30th, and 38th weeks of gestation), 13 were
      preeclamptic pregnant women (37th week of gestation; mean blood pressure, 158/99
      mm Hg), and 5 were nonpregnant controls. We compared blood M-CSF and TAT levels
      among them. Results showed that blood M-CSF and TAT levels increased
      significantly with gestational age. Furthermore, the ratio of increase in M-CSF
      was significantly lower than that in TAT in normal pregnant women compared with
      controls. In contrast, the ratio of increase in M-CSF was significantly higher
      than that in TAT in preeclamptic women compared with normal pregnant women. These
      results concerning the ratio of increase in M-CSF and TAT have not been reported.
      These findings show that M-CSF level increases significantly in preeclampsia even
      in its earlier stage, exhibiting a systolic blood pressure of less than 160 mm
      Hg.

PMID- 9537641
TI  - Urinary levels of bombesin-related peptides in a population sample from northern
      Italy: potential role in the pathogenesis of chronic obstructive pulmonary
      disease.
AB  - Bombesin-related peptides (BRP) are present in the lung and have various
      biological functions, including modulation of lung maturation. Many recent
      studies have suggested that BRP have a pathogenic role in airway wall remodeling
      in chronic obstructive pulmonary disease. The aim of this cross-sectional survey
      was to evaluate the distribution of urinary BRP excretion as a indirect marker of
      pulmonary BRP production and to assess the prevalence of smoking, chronic
      respiratory symptoms, chronic obstructive pulmonary disease, and asthma in a
      population sample from northern Italy. Associations between urinary BRP excretion
      and several respiratory and nonrespiratory variables were also evaluated. The
      only variable tested that was significantly predictive of high urinary levels of
      BRP was the presence of respiratory symptoms. In contrast to previous studies,
      smoking per se was not significantly associated with urinary BRP levels.

PMID- 9537642
TI  - Molecular genetics of familial Alzheimer disease.
AB  - Alzheimer disease (AD) is a genetically heterogeneous and progressive
      degenerative disorder of the brain. It affects approximately 4 million Americans
      and causes more than 100,000 deaths each year, and there is no cure. It is
      estimated that by the year 2020, 14 million Americans will be affected by the
      disease. Although the major pathology is confined to regions of the brain, some
      patients show an impaired sense of smell and selective loss of retinal ganglion
      cells. The biochemical processes that lead to AD are largely unknown. Genetic
      studies on inherited AD have identified three genes that when mutated can cause
      an early-onset form of the disease. Mutation of these genes has been shown to
      increase the production of a unique protein called beta-amyloid, which is the
      predominant component of neuritic plaques found in the brain of AD patients.
      Also, one susceptibility gene has been shown to be associated with the risk of
      late-onset AD in both familial and sporadic forms. The available data support to
      a large extent the amyloid cascade hypothesis as a mechanism of the disease
      pathology. The newly identified "AMY plaques" and the future identification of
      other susceptibility genes may give further clues to the neurodegenerative
      mechanisms of AD.

PMID- 9537643
TI  - Sudden cardiac death in a teenager: a review of Kawasaki disease.

PMID- 9537644
TI  - Hyperhomocysteinemia and premature vascular occlusive disease.
AB  - Hyperhomocysteinemia has recently been identified as an independent risk factor
      for arterial and venous occlusive disease. In particular, hyperhomocysteinemia
      has been associated with premature vascular disease, and may act synergistically
      with other risk factors. Two young patients with severe premature vascular
      disease, one venous and one arterial, have significantly elevated homocysteine
      levels. In addition to appropriate anti-coagulant therapy, these patients receive
      B6 and folate vitamin therapy which normalizes the homocysteine levels. While
      this course of therapy is prudent, no prospective clinical trials have yet
      demonstrated that reduction of homocysteine levels correlates with a decreased
      cardiovascular risk.

PMID- 9537645
TI  - Melatonin: receptor-mediated events that may affect breast and other steroid
      hormone-dependent cancers.
AB  - Epidemiological studies have suggested a possible link between extremely low
      frequency electromagnetic fields (EMFs) and increased rates of certain cancers.
      One cancer that has been postulated to be associated with EMF exposure is breast
      cancer, for which increased rates have been reported among electricians. These
      cancer associations are weak, and the link to EMF exposures remains tenuous.
      Understanding the mechanisms by which EMFs could have biological effects will
      help in elucidating the risk, if any, from EMFs. One hypothesis that has received
      considerable attention involves reduction of melatonin levels by EMFs. This
      hypothesis suggests that loss of melatonin affects a variety of hormonal
      processes such as estrogen homeostasis and thereby may increase breast cancer
      rates. Since this theory was first presented, putative melatonin receptors have
      been cloned, providing new tools with which to examine melatonin's mechanism of
      action and the melatonin hypothesis. These receptors are found in nuclear and
      membrane fractions of cells. The nuclear receptors (retinoid Z receptors) are
      found both in the brain and in non-neural tissues, whereas the membrane-bound
      receptors are found primarily in neural tissue and have a higher affinity for
      melatonin. These receptors may control a variety of hormonal and immunological
      functions, including the release of gonadotropins from the hypothalamus and
      pituitary and 5-lipoxygenase activity in B lymphocytes. This Working Hypothesis
      briefly reviews our current knowledge of melatonin receptors and then provides
      theories on how the inactivation of melatonin receptors may cause cancer and
      suggests areas of research for addressing this question.

PMID- 9537647
TI  - Analysis of the p16 tumor suppressor gene in early-stage prostate cancer.
AB  - To identify whether alterations of the p16 tumor suppressor gene are a common
      event in localized prostate cancer, we examined the frequency of p16 gene
      mutations in 30 primary tumors. Only two tumors demonstrated altered single
      strand conformation polymorphism patterns for exon 2 of p16. In both cases,
      sequencing revealed a missense at codon 148, a G-->A transition that resulted in
      the replacement of the alanine by threonine. Polymerase chain reaction-single
      strand conformation polymorphism analysis of matched blood samples revealed the
      same abnormal band shifts as the tumor samples, suggesting that these base
      changes are polymorphic. In addition, transcriptional inactivation by means of
      CpG island methylation has also been reported as a possible means of p16 gene
      inactivation. To address this point, we determined the pattern of DNA methylation
      at the Smal site for 21 of 30 samples for which DNA was available. Only one
      sample had an altered methylation pattern at the Smal site downstream of exon 1
      of the p16 gene, which is outside the CpG island and is not normally associated
      with transcriptional inactivation. However, two samples did have deletions
      proximal to or within the p16 gene. These results indicate that mutations in p16
      may not be a dominant pathway for p16 loss of function or that inactivation of
      p16 by DNA methylation may not be necessary for the transformation and
      progression of prostate cancer.

PMID- 9537646
TI  - Secretion of neu differentiation factor-like polypeptides by cph-transformed
      fibroblasts: cloning and characterization of Syrian hamster neuregulin cDNAs.
AB  - We reported previously that expression of the cph oncogene in Syrian hamster and
      mouse cells leads to the secretion of a polypeptide factor or factors
      structurally and functionally related to neu differentiation factor (NDF) and the
      establishment of an autocrine loop mediated through the simultaneous
      overexpression of the erbB4 receptor. To identify the nature of this factor and
      to characterize its role in the neoplastic conversion of Syrian hamster embryo
      cells, we cloned cDNAs hybridizing to rat NDF-derived probes by screening a
      library prepared from neoplastic 81C39 cells, which harbor an activated cph
      oncogene and secrete active NDF-like polypeptides. Sequence analysis of the
      isolated clones revealed a high level of homology between the hamster neuregulin
      and its rat and human counterparts and the existence of various neuregulin cDNA
      variants in Syrian hamster cells, presumably originating from alternatively
      spliced RNA species. Interestingly, some of these neuregulin cDNAs were longer
      (up to 5.5 kb) than those isolated before from any other system, suggesting that
      the Syrian hamster neuregulin precursor mRNA accumulates at greater
      concentrations than in other species. We also detected different hamster
      neuregulin protein isoforms by using in vitro transcription-translation analyses.
      Peptide sequence analysis identified the major NDF-like polypeptide secreted by
      81C39 cells as an alpha2b-neuregulin. Northern blot analyses with the cloned cDNA
      inserts showed that neuregulin overexpression was commonly associated with the
      neoplastic conversion of chemically initiated hamster embryo fibroblasts. This,
      along with the detection of elevated erbB2- or erbB4-specific transcripts in most
      (six of eight) neoplastic cell lines tested, supports the notion that autocrine
      neuregulin signaling plays an important role in maintaining the transformed
      phenotype by providing a growth advantage to cph-transformed cells.

PMID- 9537648
TI  - p53-independent WAF1 induction by ACNU in human glioblastoma cells.
AB  - The induction of WAF1 gene expression after the treatment with the anticancer
      agent 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea
      hydrochloride (ACNU; nimustine hydrochloride) was studied in two human
      glioblastoma cell lines: U-87MG, which bears the wild-type p53 gene, and T98G,
      which bears the mutant p53 gene. A marked accumulation of WAF1 was observed 3 h
      after ACNU treatment in both cell lines. The induction of WAF1 mRNA by ACNU was
      detected by northern blot analysis in these cells. Binding activity of p53 to a
      p53 consensus sequence increased after treatment in U-87MG cells but not in T98G
      cells. The existence of a p53-independent WAF1 induction pathway was supported by
      the apparent accumulation of WAF1 after ACNU treatment in the p53-null human
      osteosarcoma cell line Saos-2. These findings suggest that there are two possible
      pathways for WAF1 induction: the p53-dependent pathway through the p53-responsive
      element and the p53-independent pathway through other elements.

PMID- 9537649
TI  - Role of tumor suppressor genes in transplacental lung carcinogenesis.
AB  - Most human cancers involve multiple genetic changes, including activation of
      oncogenes such as Ki-ras-2 (Kras2) and inactivation of any one of a number of
      tumor suppressor genes such as p53 and members of the retinoblastoma (Rb)
      regulatory axis. As part of an ongoing project to determine how in utero exposure
      to chemical carcinogens affects the molecular pathogenesis of murine lung tumors,
      the p53 and p16Cdkn2a genes were analyzed by using paraffin-embedded lung tissues
      from mice treated transplacentally with 3-methylcholanthrene. Single-strand
      conformation polymorphism analysis of exons 5-8 of the p53 gene, as well as their
      flanking introns, demonstrated an absence of mutations at this gene locus.
      However, a genetic polymorphism was identified at nt 708 in intron 4 of the DBA/2
      strain of mice 5 bp downstream of a 3' branching-point splice signal. Analysis of
      exons 1 and 2 of the Cdkn2a gene by single-strand conformation polymorphism and
      sequence analyses revealed mutations in exon 2 in 7% of the tumors examined.
      Tumor 23-1 exhibited a CAC-->TAC transition at nt 301 (His74-->Tyr74), and tumor
      36-1 exhibited a GGG-->GAG transition at nucleotide 350 (Gly90-->Glu90). Northern
      blot analysis of 14 of the larger tumors showed a marked decrease in the levels
      of Rb RNA expression. Immunohistochemical analysis revealed a spectrum of pRb
      expression, with the smaller adenomas showing moderate numbers of nuclei with
      heterogeneous staining for pRb in contrast with a highly reduced or near-complete
      absence of expression in the nuclei of larger tumors with features of
      adenocarcinomas. The low incidence of mutations at tumor suppressor loci
      suggested that inactivation of tumor suppressor genes was a late event in murine
      lung tumor pathogenesis. The identification of both mutations at the Cdkn2a gene
      locus and reduced levels of Rb expression combined with previous studies
      demonstrating a high incidence of mutated Kras2 alleles in these tumors implies
      that alterations of the Rb regulatory axis, in combination with mutation of
      Kras2, may be the preferred pathway for the pathogenesis of pulmonary tumors in
      transplacentally exposed mice.

PMID- 9537650
TI  - Alterations in the expression of alpha6beta4 integrin and p21/WAF1/Cip1 in N
      nitrosomethylbenzylamine-induced rat esophageal tumorigenesis.
AB  - Integrin alpha6beta4 is altered in many neoplastic cells, but no data exist to
      show this happens in esophageal neoplasms. To examine the expression of this
      integrin in rat esophageal tumorigenesis induced by N-nitrosomethylbenzylamine
      (NMBA), (alpha6 and beta4 expression was evaluated in normal esophageal
      epithelium, in NMBA-induced preneoplastic lesions, and in papillomas by
      quantitative reverse transcription (RT)-polymerase chain reaction (PCR) and
      immunohistochemical analysis. Because the 34 subunit of this integrin has been
      found to cause cell-cycle arrest by the induction of p21/WAF1/Cip1, the
      expression of p21/WAF1/Cip1 was also analyzed by RT-PCR. Compared with the levels
      in normal epithelium, the alpha6A, alpha6B, and beta4 integrin levels in
      esophageal papillomas were 1.9-, 2.2-, and 2.1-fold lower, respectively. RT-PCR
      analysis showed no significant differences in integrin levels between
      preneoplastic and normal samples, and northern blot analysis of the beta4
      integrin produced results in agreement with the RT-PCR results. The p21/WAF1/Cip1
      level was decreased 1.6-fold in preneoplastic tissues and 3.1-fold in papilloma
      samples when compared with the mRNA levels in normal epithelium. Immunostaining
      showed that alpha6beta4 integrin was localized at the basolateral surface of the
      basal cells in normal esophageal epithelium. In preneoplastic lesions, however,
      the expression of this integrin was not polarized and was expressed in basal
      cells as well as in suprabasal cells. Beta4 expression was significantly reduced
      and alpha6A expression was decreased and delocalized in papillomas. These
      findings suggest that alteration in alpha6beta4 integrin and p21/WAF1/Cip1
      expression may be an important biomarker for tumor progression in NMBA-induced
      rat esophageal tumorigenesis.

PMID- 9537651
TI  - v-src activation of the collagenase-1 (matrix metalloproteinase-1) promoter
      through PEA3 and STAT: requirement of extracellular signal-regulated kinases and
      inhibition by retinoic acid receptors.
AB  - Collagenase-1 (matrix metalloproteinase-1 (MMP-1)) degrades the extracellular
      matrix and enhances the invasive phenotype of tumor cells. v-src activated MMP-1
      transcription through a series of elements in the proximal promoter, including
      the E2BP (nt -172), polyoma virus enhancer A3 (PEA3) (nt -94), activator protein
      1 (AP-1) (nt -72), and signal transducer and activator of transcription (STAT)
      (nt -57) consensus sites. Of these sites, PEA3 and STAT contributed specifically
      to induction by v-src, whereas the remaining elements were also involved in
      induction by the phorbol ester phorbol myristate acetate (PMA). However, in
      contrast to MMP-1 induction by PMA, an AP-1 site located at nt -186 did not
      contribute to v-src induction. These results suggest divergence of the tyrosine
      kinase- and protein kinase C-dependent pathways with respect to MMP-1
      transcription. v-src induced MMP-1 through mitogen-activated protein kinases,
      with extracellular signal-regulated kinases playing a larger role than c-jun N
      terminal kinase. Retinoic acid, which inhibits the progression of certain
      cancers, repressed v-src-induced MMP-1 transcription. Constitutive expression of
      retinoic acid receptors (RARs) alpha or beta, but not gamma, or of retinoid X
      receptor alpha, repressed v-src-induced collagenase-1 transcription. We concluded
      that oncogenic induction of MMP-1 by v-src depends on signaling pathways and cis
      acting sequences that are distinct from those involved in phorbol ester
      activation. Furthermore, v-src induction of MMP-1 may, by acting in concert with
      other genes, enhance matrix degradation and tumor progression, and retinoic acid
      and RARs may antagonize this induction in an RAR type-specific manner.

PMID- 9537652
TI  - Modulation of p53 protein conformation and DNA-binding activity by intracellular
      chelation of zinc.
AB  - The transcription factor p53 controls the proliferation and survival of cells
      exposed to DNA damage. The specific DNA-binding domain of p53 (residues 102-292)
      has a complex tertiary structure that is stabilized by zinc. In this study, we
      showed that exposure of cultured cells to the membrane-permeable chelator N,N,N',
      N'-tetrakis(2-pyridylmethyl)ethylenediamine induced wild-type p53 to accumulate
      in an immunologically "mutant" form (PAb240+, PAb1620-) with decreased DNA
      binding activity. Removal of N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine
      from culture medium allowed p53 to refold into the immunologically wild-type
      form, followed by a transient increase in DNA binding, expression of the cyclin
      dependent kinase inhibitor p21WAF1, and cell-cycle delay in the G1 phase. Thus,
      modulation of intracellular zinc induced conformational changes in p53 that
      activated wild-type function, suggesting that metalloregulation may play a role
      in controlling p53.

PMID- 9537653
TI  - Dispensability of p53 degradation for tumorigenicity and decreased serum
      requirement of human papillomavirus type 16 E6.
AB  - Certain types of human papillomavirus (HPV), such as types 16 and 18, are
      etiological agents for carcinogenesis of the uterine cervix. These HPVs have two
      oncogenes, E6 and E7, that have transforming activities in established murine
      cells. Tumorigenicity and decreased serum requirement for cell growth are
      conferred by the E6 gene, whereas anchorage-independent growth is mainly governed
      by the E7 gene. To understand the mechanism of cellular transformation by the
      HPV16 E6 gene, we examined three mutant E6 proteins defective for p53 binding,
      p53 degradation, or transactivation of the adenovirus E2 promoter for the ability
      to induce tumorigenicity and decreased serum requirement. The results showed that
      tumorigenicity and decreased serum requirement were associated with the ability
      of E6 to bind to p53, although the subsequent degradation of p53 was not required
      for these functions.

PMID- 9537654
TI  - Vascular and visceral injuries associated with lumbar disc surgery: medicolegal
      implications.
AB  - Symptomatic perforation of the anterior annulus fibrosus/anterior longitudinal
      ligament during surgery for herniated lumbar disc disease is one of the more
      solemn and sobering complications experienced by neurosurgeons or orthopedic
      surgeons. This complication frequently results in the death of the patient. Its
      occurrence is probably more common than the medical community would expect. The
      authors report 21 cases since 1985 in which an injury to an intra-abdominal
      vessel or viscera occurred. In all cases litigation resulted and a settlement or
      verdict was rendered. A review of the literature is presented and the medicolegal
      implications of symptomatic ventral perforations of the annulus fibrosus/anterior
      longitudinal ligament are discussed.

PMID- 9537655
TI  - The effect of incomplete patient follow-up on the reported results of AVM
      radiosurgery.
AB  - BACKGROUND: The reported efficacy of AVM radiosurgery--80-85% 2-year obliteration
      rate--is based exclusively on the results of follow-up arteriography in a small
      percentage of treated patients; it is therefore inaccurate. We examined the
      effect of incomplete follow-up on the results of AVM radiosurgery. METHODS: We
      reviewed the results of AVM radiosurgery in 82 patients after a minimum of 24
      months of follow-up. Patients were not preselected to undergo arteriography on
      the basis of any other imaging study. Data were analyzed using the Kaplan-Meier
      method and stratified by size of AVM. Results were compared with those obtained
      from the same data using the reporting techniques described in the literature.
      RESULTS: When data analysis was limited to patients who had follow-up
      arteriography, the 2-, 3-, and 4-year obliteration rates were 37%, 73%, and 84%
      after a minimum 24-month follow-up. Using Kaplan-Meier analysis the 2-, 3-, and 4
      year obliteration rates were 32%, 55%, and 55% (95% CI = +/-18%), respectively.
      The 2-year obliteration rate was 43% for AVMs <30 mm in diameter and 16% for AVMs
      >30 mm in diameter, respectively. CONCLUSION: If data analysis is limited to the
      patients who undergo follow-up arteriography, the obliteration rate of AVM
      radiosurgery is overestimated. The actual 2-year obliteration rate if all data is
      considered is in the range of 40% rather than the commonly reported 80%.
      Therefore, treated patients are exposed to the risk of intracerebral hemorrhage
      for a longer period than previously appreciated. Compulsive long-term follow-up
      is required to document the true AVM obliteration rate after treatment by
      radiosurgery.

PMID- 9537656
TI  - Radiation-related adverse effects observed on neuro-imaging several years after
      radiosurgery for cerebral arteriovenous malformations.
AB  - BACKGROUND: To our knowledge, there are no reported arteriovenous malformation
      (AVM) series in which detailed long-term follow-up results after radiosurgery
      were described based on the whole patient group. METHOD: We performed a detailed
      long-term follow-up study of 53 patients with cerebral AVMs treated with gamma
      knife (GK) radiosurgery, with emphasis on radiation-related adverse effects
      detected on neuro-imaging after a long post-irradiation latency period (3-10
      years). The post-GK follow-up period was 40-232 months excluding two mortalities,
      the mean being 112 and the median being 111 months. RESULTS: Three patients
      (5.6%) have, as yet, refused all neuro-imaging follow-up studies. Complete nidus
      obliteration was confirmed angiographically in 32 patients (60.4%) between 1 and
      5 post-GK years. In the other 18 patients (34%), despite significant nidus
      shrinkage being angiographically demonstrated, complete obliteration was not
      achieved during a 2-7 year follow-up period. There were two mortalities, one AVM
      related (massive re-bleeding during the latency period) and the other angiography
      related. There were five radiation-related morbidities (9.4%), three of which
      hemi-Parkinson syndrome, hemiparesis, and visual field disturbances attributable
      to delayed cyst formation-manifested at 5.5, 7 and 7 post-GK years, respectively.
      We also experienced five patients (9.4%) in whom, despite remaining asymptomatic
      to date, radiation-related adverse effects were seen on neuro-imaging: middle
      cerebral artery stenosis at 3 post-GK years in one patient; dural arteriovenous
      fistula at 7 post GK-years in one; delayed cyst formation in two, at 5 and 10
      post-GK years; and a small cavitation at 9 post-GK years. CONCLUSION: Long-term
      follow-up, particularly with neuro-imaging modalities, is essential even after
      the "treatment goal" has been attained.

PMID- 9537657
TI  - The significance of retrograde thrombosis following removal of arteriovenous
      malformations in elderly patients.
AB  - BACKGROUND: Retrograde thrombosis of former feeding arteries should be considered
      as a distinct postoperative complication following surgery for arteriovenous
      malformation (AVM). Regardless of the presence of AVMs, the cerebral arteries
      undergo atherosclerotic changes with advancing age. In the present study, three
      cases in elderly patients who developed retrograde thrombosis are reported, and
      the effect of the patient's age on this complication is discussed. CLINICAL
      MATERIALS AND METHODS: The present study group consisted of 158 patients who
      underwent AVM resection and postoperative angiographic studies. Five patients
      were 65 years of age or older (elderly group) at the time of operation, 108 were
      between 20 and 64 years of age (adult group), and 45 were less than 20 years of
      age (young group). The incidence of retrograde thrombosis in the elderly group
      was compared with that of the other two groups. RESULTS: We found that surgery in
      the elderly group was accompanied by a significantly higher incidence of
      retrograde thrombosis (60%) than in the adult group (4%), or the young group
      (0%). CONCLUSIONS: The present study suggests that this complication should be
      considered as a serious possibility following removal of an AVM, especially in
      elderly patients.

PMID- 9537658
TI  - Postoperative hyperperfusion in dural arteriovenous fistula associated with
      venous ischemia: case report.
AB  - BACKGROUND: It is well known that carotid endarterectomy and extracranial
      intracranial arterial bypass sometimes cause postoperative hyperperfusion, and
      vasoparalysis attributable to long-standing ischemia has been suggested as the
      cause. It is also well known that dural arteriovenous fistula (AVF) sometimes
      causes cerebral ischemia attributable to venous hypertension. However, there are
      few reports regarding the postoperative changes of regional cerebral blood flow
      (rCBF). METHODS: We report a case of dural AVF of the left transverse/sigmoid
      sinuses, occurring in a 64-year-old man. Intraoperative transvenous embolization
      combined with transarterial embolization was performed, and the rCBF was measured
      pre- and postoperatively using 99mTc-hexamethyl-propylene amine oxime and single
      photon emission computed tomography (SPECT). RESULTS: Preoperative SPECT
      disclosed a marked rCBF reduction in the left temporal, parietal, and occipital
      lobes. Complete obliteration of the AVF was attained after the intraoperative
      transvenous embolization, without any neurological deterioration. However,
      postoperative SPECT demonstrated temporary hyperperfusion in these regions.
      CONCLUSIONS: Sudden resolution of venous ischemia can lead to postoperative
      hyperperfusion, and pre- and post-treatment rCBF studies are important to prevent
      complications related to hyperperfusion.

PMID- 9537659
TI  - Effect of hyperbaric oxygen therapy on survival after global cerebral ischemia in
      rats.
AB  - BACKGROUND: Hyperbaric oxygenation (HBO) has been considered for many years for
      the treatment of severe brain ischemia. However, its efficacy has not been
      proven. The aim of this study was to shed light on this question. METHODS: Acute
      global cerebral ischemia was induced in 18 rats using the four-vessel occlusion
      model. Regional cerebral blood flow (CBF) was determined by laser-Doppler
      flowmetry using a flexible 1 mm fiberoptic probe. Two stainless steel screws were
      used to measure the spontaneous electrical activity from the contralateral
      hemisphere. After ischemia monitored by laser-Doppler flowmetry and ECoG, the
      animals were divided into two groups: (1) control animals that breathed air at
      atmospheric pressure and (2) rats exposed to HBO at three atmospheres absolute
      pressure (ATA) for 1 hour. Survival time and rate were recorded for both groups
      of animals for 14 days. RESULTS: The survival rate in the study group was
      significantly higher (45%) than in the control group (0%). In the animals that
      did not survive the 14-day period, those exposed to HBO survived longer than the
      control animals (59.8+/-9.1 hour versus 17.9+/-2.7 hours, p < 0.05). CONCLUSION:
      This investigation demonstrates that HBO administered after global cerebral
      ischemia can increase survival in a rat stroke model.

PMID- 9537660
TI  - Internal thoracic-carotid bypass surgery for Takayasu's arteritis.
AB  - BACKGROUND: Various carotid reconstructions have been used in Takayasu's
      arteritis (TA) to relieve brain ischemic insult. The indications and guidelines
      for surgical management, however, have remained poorly defined. The authors
      present a new reconstructive procedure using the sequential internal thoracic
      artery (ITA) as the donor for bypass surgery to supplement the cerebral blood
      flow. CASE DESCRIPTION: A 38-year-old woman presented with three episodes of
      syncope. The patient was admitted to our hospital and was diagnosed with TA.
      Before the operation, the patient was designated to undergo aortocarotid bypass
      using saphenous veins. However, a dilated ascending aorta with an extremely thin
      wall made it impossible. Finally, we decided to use the ITA as the donor for
      bypass surgery. This patient is now free of cerebral ischemic insult 8 months
      after the operation. CONCLUSION: Although the procedure is still at a preliminary
      stage, a successful case is briefly described.

PMID- 9537661
TI  - Monitoring of cerebral hemodynamics using near-infrared spectroscopy during local
      intraarterial thrombolysis: case report.
AB  - BACKGROUND: The efficacy of continuous measuring of changes in regional
      cerebrovascular hemoglobin saturation during local intraarterial thrombolytic
      therapy for middle cerebral artery (MCA) occlusion is discussed. METHODS: To
      obtain real-time data on changing cerebral hemodynamics, near-infrared
      spectroscopy (NIRS) was used during recanalization of an occluded MCA branch.
      Changes in regional cerebrovascular hemoglobin saturation of the affected left
      frontal lobe were observed immediately after intraarterial injection of urokinase
      (UK). RESULTS: A steady increase in regional oxygen saturation (rSO2) was
      observed until recanalization was confirmed angiographically as a result of
      300,000 IU of UK. CONCLUSIONS: Monitoring of cerebrovascular hemoglobin
      saturation by NIRS is a simple, noninvasive technique suggesting its potential
      for intraoperative monitoring during interventional neuroradiologic procedures.

PMID- 9537662
TI  - Treatment of acute superior sagittal sinus thrombosis by t-PA infusion via
      venography--direct thrombolytic therapy in the acute phase.
AB  - BACKGROUND: Dural sinus thrombosis is a relatively rare syndrome, often with a
      very poor prognosis. Systemic anticoagulant therapy has produced poor results;
      therefore rapid recanalization of the affected vessels is essential. The recent
      advancements in angiographic technique and catheter technology enable us to
      perform direct selective venography. CASE REPORT: We observed a case of acute
      superior sagittal sinus thrombosis in a pregnant woman. The patient's
      consciousness level and motor function gradually deteriorated. Direct
      thrombolysis was performed via venography. RESULTS: The patient was treated
      successfully by thrombolysis with infusion of t-PA via selective venography
      within 2 days of rapid clinical deterioration and sustained a dramatic
      improvement of her neurological deficits. CONCLUSIONS: Direct thrombolysis via
      selective venography is considered a safe and useful treatment for dural sinus
      thrombosis in the acute phase.

PMID- 9537663
TI  - Sagittal sinus thrombosis following minor head injury treated with continuous
      urokinase infusion.
AB  - BACKGROUND: Cerebral dural sinus thrombosis is a rare clinical entity. Symptoms
      may be vague, and left untreated thrombus progression may be fatal because of
      venous congestion and infarction. METHODS: We report a case of post-traumatic
      dural sinus thrombosis treated with selective transfemoral, transvenous
      catheterization and infusion of urokinase. RESULTS: Urokinase infusion into the
      dural venous sinuses using a microcatheter introduced from the femoral vein was
      successfully carried out, and patency of the venous sinuses was reestablished.
      CONCLUSION: Venous sinus thrombosis can be an overlooked sequel to head injury.
      If the diagnosis is entertained, prompt performance of appropriate imaging
      studies should be instituted so that therapy can be initiated. The use of
      selective sinus catheterization using microcatheter techniques with instillation
      of urokinase is an excellent mode of therapy that should be considered in any
      patient with symptomatic occlusion.

PMID- 9537664
TI  - The significance of lack of MR contrast enhancement of supratentorial brain
      tumors in adults: histopathological evaluation of a series.
AB  - BACKGROUND: To correlate magnetic resonance imaging (MRI) findings of non
      enhancement of supratentorial brain neoplasms in adults with histopathologic
      findings. METHODS: Forty adult patients whose preoperative MRI studies
      demonstrated a non-enhancing supratentorial brain neoplasm were identified
      retrospectively. Biopsy material for all patients was then reviewed by a board
      certified neuropathologist. RESULTS: Histopathologic examination identified 24
      (60%) low-grade gliomas: 4 (10%) low-grade astrocytomas, 10 (25%) low-grade
      gliomas (not further classified), 8 (20%) low-grade oligodendrogliomas, and 2
      (5%) low-grade mixed oligoastrocytomas. However, 16 (40%) nonenhancing lesions
      were classified as anaplastic gliomas: 12 (30%) anaplastic astrocytomas, 1 (2.5%)
      anaplastic mixed oligoastrocytoma, 1 (2.5%) anaplastic oligodendroglioma, and 2
      (5%) anaplastic infiltrating gliomas of indeterminate subtype. CONCLUSION: Non
      enhancement of supratentorial brain neoplasms in adults does not equate with low
      grade malignancy. This fact should be taken into account when biopsy and
      treatment are being planned in patients with nonenhancing brain tumors. More
      aggressive and/or surgical therapy might be indicated for such lesions,
      particularly those in the nondominant hemisphere or nonmotor areas.

PMID- 9537665
TI  - Sarcoma metastatic to the brain: a series of 15 cases.
AB  - METHODS: We report on 15 patients surgically treated for intraparenchymal brain
      metastases from sarcoma, including six osteosarcomas, five leiomyosarcomas, two
      malignant fibrous histiocytomas, and two alveolar soft-part sarcomas (ASPS).
      RESULT: Median survival after craniotomy was 9.3 months. Patients with a
      preoperative Karnofsky performance score of > 70 survived for 12.8 versus 5.3
      months for those with a Karnofsky performance score < 70 (p=0.03). Patients with
      evidence of only lung metastases at the time of surgery (nine cases) survived 8.6
      months, which was similar to the 10.4-month survival for patients with disease
      limited to the brain (p=0.1). The two patients with alveolar soft-part sarcomas
      are alive at 15 and 20 months after surgery. CONCLUSION: We conclude that surgery
      is effective in treating selected patients with sarcoma metastatic to the brain
      and that patients with metastasis from ASPS may have a relatively good prognosis
      if they are surgically treated. The complete removal of all brain metastases and
      a Karnofsky performance score > 70 are associated with a favorable prognosis; the
      presence of concurrent lung metastases is not a contraindication to surgery.

PMID- 9537666
TI  - Anaplastic ganglioglioma with dissemination to the spinal cord: a case report.
AB  - BACKGROUND: Gangliogliomas are rare tumors that generally arise in the temporal
      lobe. Although most are benign, malignant gangliogliomas have been reported. The
      clinical course of anaplastic gangliogliomas has not been well understood. CASE
      REPORT: An anaplastic ganglioglioma of the right parieto-occipital lobe is
      reported in a 7-year-old girl who presented with left homonymous hemianopsia and
      papilledema. Neurologic examination revealed a choked disc and a left homonymous
      hemianopsia. A computed tomographic scan and magnetic resonance imaging showed a
      large enhancing mass with calcification. Radiation therapy was administered after
      subtotal resection of the tumor. Histologic and immunohistochemical studies
      showed a typical appearance of anaplastic ganglioglioma. Spinal dissemination
      developed 3 months after the operation. In spite of spinal axis radiation and
      chemotherapy, she expired 15 months after the diagnosis. CONCLUSION: Although the
      clinical course of anaplastic gangliogliomas is not always aggressive, our case
      indicates the importance of strict follow-up assessments of the whole
      craniospinal axis.

PMID- 9537667
TI  - Antiepileptic drug review: part 1.

PMID- 9537668
TI  - Making our specialty superior.

PMID- 9537669
TI  - Lessons from India.

PMID- 9537670
TI  - Neuropeptide families: evolutionary perspectives.
AB  - Examination of neuropeptide families can provide information about phyletic
      relationships and evolutionary processes. In this article the
      oxytocin/vasopressin family, growth hormone releasing factor (GRF) superfamily
      and the substance P/tachykinin family have been considered in detail because they
      have been isolated from an extraordinarily diverse array of species from several
      vertebrate classes and invertebrate phyla. More important is that the nucleotide
      sequence of mRNA or cDNA encoding many of these peptides has been determined,
      which has allowed evolutionary distances to be estimated based on the DNA
      mutation rate. The origin of a given family lies in a primordial gene that arose
      many millions of years ago, and through time, exon duplication and insertion,
      gene duplication, point mutation and exon loss, the family developed into the
      forms that are now recognised. For example, in birds, GRF and pituitary adenylate
      cyclase activating peptide (PACAP) are encoded by the same gene, which probably
      arose as a result of exon duplication and tandem insertion of the ancestral GRF
      gene. In mammals GRF is the sole product on one gene, and PACAP is the product of
      a gene that also produces PACAP-related peptide (PRP), which is homologous to
      GRF. Thus it appears that between birds and mammals the GRF/PACAP gene
      duplicated: exon loss gave rise to the mammalian GRF gene, while mutation led to
      the formation of the mammalian PRP/PACAP gene. The neuropeptide Y superfamily is
      considered briefly, as is cionin, which is an invertebrate peptide that is
      closely related to the mammalian gastrin/cholecystokinin family.

PMID- 9537671
TI  - The angiotensin II binding site on Mycoplasma hyorhynis is structurally distinct
      from mammalian AT1 and AT2 receptors.
AB  - Angiotensin II (AngII) binding sites were characterized on rat pheochromocytoma
      cells (PC-12) which are known to express exclusively the type-2 (AT2) AngII
      receptor. Interestingly, we found that, on confluent PC-12 cells, only partial
      inhibition of 125I-AngII binding was achieved when cells were incubated with a
      saturating concentration of PD-123 319 (an AT2 selective ligand) suggesting the
      presence of an atypical binding site. In binding experiments, AngII exhibited
      high affinity for this atypical binding site with a dissociation constant (Kd) of
      16 nM. Moreover, bacitracin potently inhibited PD-123 319-resistant 125I-AngII
      binding with an IC50 half-maximal inhibitory concentration of 44 microM. Enzyme
      immunoassay revealed that the cells were contaminated with Mycoplasma hyorhynis.
      Contaminated PC-12 cells were photolabeled with 125I-[p-benzoylPhe1]AngII and
      covalently labeled proteins were subjected to polyacrylamide gel electrophoresis
      followed by autoradiography. Under these conditions, two distinct labeled species
      of 140 kilodaltons (kDa) and 95 kDa were detected. Deglycosylation of the 140 kDa
      labeled AT2 receptor with glycopeptidase-F (PNGase-F) resulted in a 35 kDa
      protein whereas the 95 kDa band was not affected by digestion with the
      endoglycosidase. Thus, our results show that the AngII binding site on M.
      hyorhynis is structurally distinct from mammalian AT1 and AT2 receptors.

PMID- 9537672
TI  - Role of endogenous endothelin-1 in stress-induced gastric mucosal damage and acid
      secretion in rats.
AB  - In rats subjected to 8 h water-immersion stress, gastric and duodenal mucosal
      hemorrhage and erosions were detected by macroscopic and histopathological
      examination. Moreover, plasma and gastric mucosal endothelin-1 (ET-1) levels rose
      appreciably in a time-related manner during water immersion, with a higher
      concentration detected in gastric mucosa. Thus, the percentage increases in
      plasma (gastric mucosal) ET-1, relative to basal levels, after 1, 4 and 8 h of
      water immersion were 86(172), 169(322) and 210(391)%, respectively. Likewise, a
      marked increase of gastric acid output was demonstrated 30 min after water
      immersion and lasted for 3 h. Pretreatment with the endothelin ET(A)/ET(B)
      receptor blocker, bosentan (30 and 100 mg kg(-1)), orally, dose-dependently
      antagonized gastric and duodenal mucosal damage as indicated by reductions in
      lesion lengths of 67 and 80%, respectively. Similar protective effects on mucosa
      were observed when bosentan was given by the intramuscular route. On the other
      hand, bosentan suppressed the rate of acid output by 30.3+/-2.1% in the stressed
      rats, but had no such effect in non-stressed animals. Taken together, results
      from this study implicate the endogenous peptide, ET-1, as a powerful mediator of
      stress-evoked gastro-duodenal mucosal damage and, moreover, present bosentan as a
      potential protector against hyperacidity and mucosal erosion that occur as a
      consequence of stress.

PMID- 9537673
TI  - Role of Lys215 located in the fifth transmembrane domain of the AT2 receptor in
      ligand-receptor interaction.
AB  - Studies on ligand-receptor interaction of Angiotensin II (Ang II) receptor type 1
      have shown that for peptidic ligands to bind this receptor they must interact via
      their C-terminal carboxylate group to the positively charged side chain of the
      Lysine residue 199 located in the fifth transmembrane domain of this receptor. In
      the Ang II receptor type AT2, this Lysine residue is conserved at position 215 in
      the fifth transmembrane domain. To determine the specific mechanism of ligand
      binding to the Angiotensin II receptor type AT2, mutated AT2 receptors were
      generated in which the Lys215 was replaced with glutamic acid, glutamine, alanine
      and arginine. The ability of these mutated receptors to bind peptidic ligands
      125I-[Sar1-Ile8]Ang II (non-specific for AT2 receptor type), 125I-CGP42112A (AT2
      receptor specific) and the non-peptidic ligand PD123319 (AT2 receptor specific)
      was evaluated by expressing these receptors in Xenopus oocytes and performing
      binding assays. The Lys215Glu and Lys215Gln mutants of AT2 receptor lost their
      affinity to 125I-[Sar1-Ile8]Ang II, but retained their affinity to 125I-CGP42112A
      and PD123319. In contrast, Lys215Arg mutant retained its affinity to 125I-[Sar1
      Ile8]Ang II, but exhibited lower affinity to 125I-CGP42112A. The Lys215Ala mutant
      lost its affinity to both 125I-[Sar1-Ile8]Ang II and 125I-CGP42112A. These
      results suggest that the binding mechanism of 125I-[Sar1-Ile8]Ang II to AT2
      receptor is similar to that of AT1 receptor since an amino acid with positively
      charged side chain (Lys or Arg) located in the fifth transmembrane domain is
      required for this ligand to bind AT2 receptor. In contrast, although CGP42112A is
      a peptidic ligand, it does not require an interaction between its C-terminal
      carboxylate group and the positively charged side-chain of an amino acid in the
      fifth transmembrane domain for its binding to AT2 receptor.

PMID- 9537674
TI  - Effects of dexamethasone on the profile of cytokine secretion in human whole
      blood cell cultures.
AB  - EXPERIMENTAL OBJECTIVES: The interaction between the endocrine and immune systems
      is a very intriguing area. Endogenous glucocorticoids, as end-effectors of the
      hypothalamo-pituitary-adrenal axis, inhibit the immune and inflammatory responses
      and are used as immunosuppressive drugs in many inflammatory, autoimmune and
      allergic diseases. The aims of this study were to investigate the effects of
      dexamethasone on the profile of cytokine secretion in whole blood cell cultures
      from healthy subjects and to analyse the gender-related sensitivity to
      dexamethasone on each cytokine secretion. RESULTS: There was a significant
      inhibition by dexamethasone (from 1 to 100 nM) on the secretion of monokines (IL
      1beta, IL-6, IL-8 and TNF alpha) and lymphokines (IL-2, IL-4, IL-10 and IFN
      gamma), either after LPS or PHA stimulation (P < 0.01). Interleukin 4 and IL-10
      were less inhibited than IFN gamma (P < 0.05 at 1 nM, P < 0.01 at 10 nM and P <
      0.001 from 100 nM to 10 microM). No gender difference was observed in the rate of
      inhibition of the secretion of each cytokine. CONCLUSION: This study shows that
      the inhibition of cytokine secretion by dexamethasone is more marked on Th1-type
      cytokines than on Th2-type cytokines. These data support the idea that
      glucocorticoids may induce a shift from the Th1 to Th2 profile of cytokine
      secretion.

PMID- 9537675
TI  - Metabolism of beta-endorphin in plasma studied by liquid chromatography
      electrospray ionization mass spectrometry.
AB  - Degradation of synthetic human beta-endorphin by a human plasma proteinase was
      studied with high-performance liquid chromatography in combination with mass
      spectrometry. The peptide was metabolized at a rate of 25 pmol/min to the major
      fragments beta-endorphin (1-19) and (20-31), the latter reported as a potent
      inhibitor of morphine- and beta-endorphin-induced analgesia in mice. The
      proteinase responsible for this process was classified as a metal-dependent
      serine proteinase and was effectively inactivated by phenylmethylsulfonyl
      fluoride and ethylenediaminetetraacetic acid. Identification of the products
      formed during the enzymatic reaction was performed by liquid chromatography on
      line with electrospray mass spectrometry, using a reversed-phase or a novel size
      exclusion column capable of separating molecules between 0.1-7 kilodaltons.
      Peptide sequences were verified by tandem mass spectrometry experiments. The
      conversion of beta-endorphin may have physiological implications in the mechanism
      of pain. The obtained data suggest that several precautions should be considered
      during recovery and measurement of beta-endorphin in plasma by immunological
      techniques. The applied strategy may also be useful for studying metabolism of
      various peptidergic compounds with potential pharmacological significance.

PMID- 9537676
TI  - An amino acid mixture deficient in phenylalanine and tyrosine reduces
      cerebrospinal fluid catecholamine metabolites and alcohol consumption in vervet
      monkeys.
AB  - An amino acid mixture devoid of tryptophan, given orally, was previously shown to
      reduce cerebrospinal fluid levels of tryptophan and 5-hydroxyindoleacetic acid in
      vervet monkeys, as compared to a control mixture containing all essential amino
      acids. In the present study, we tested the possibility that a similar amino acid
      mixture containing tryptophan, but devoid of phenylalanine and tyrosine (the
      amino acid precursors of catecholamine neurotransmitters), would influence
      dopamine and noradrenaline metabolism. Five hours after the administration of
      this mixture to vervet monkeys, cerebrospinal fluid levels of homovanillic acid
      and 3-methoxy-4-hydroxyphenylethylene glycol were reduced by 27.4% and 26.9%,
      respectively. Both effects were statistically significant. Plasma tyrosine (-30%)
      and the ratio of tyrosine to the sum of other large neutral amino acids
      (sigmaLNAA) were also significantly reduced. The behavioral efficacy of
      phenylalanine/tyrosine depletion was compared with that of tryptophan depletion
      in a primate model of voluntary alcohol consumption. All three drinks lowered
      alcohol consumption, but the effects of the tryptophan-deficient amino acid
      mixture were not different from those of the balanced amino acid control. The
      phenylalanine/tyrosine-deficient drink differentially lowered alcohol
      consumption, consistent with other data in this species and elsewhere implicating
      dopamine in the rewarding effects of alcohol.

PMID- 9537677
TI  - The alpha-2a noradrenergic agonist, guanfacine, improves delayed response
      performance in young adult rhesus monkeys.
AB  - In aged monkeys with naturally occurring catecholamine depletion, alpha-2
      adrenergic agonists such as guanfacine have repeatedly been shown to improve
      dorsolateral prefrontal cortical function, as assessed by the spatial delayed
      response task. Both low (0.0001-0.001 mg/kg) and high (0.5 mg/kg) but not
      intermediate (0.01-0.05 mg/kg) doses of guanfacine improve spatial working memory
      performance in aged animals. However, it is not known whether guanfacine would
      similarly improve performance in young animals. In the present study, the effects
      of guanfacine on delayed response performance were characterized in seven young
      adult rhesus monkeys. Low doses of guanfacine (0.0001-0.01 mg/kg) had no effect
      on task performance, while high doses of guanfacine (0.1-0.7 mg/kg) significantly
      improved task performance. The highest doses produced mild sedation that was
      independent of drug effects on delayed response. The most effective dose of
      guanfacine was challenged with the alpha-2 antagonist idazoxan (0.1 mg/kg). This
      dose of idazoxan had no effect on task performance when given alone. Consistent
      with an alpha-2 mechanism, idazoxan significantly decreased delayed response
      performance in guanfacine-treated animals. These results support the hypothesis
      that delayed response performance in young intact animals can be improved through
      actions at alpha-2 adrenergic receptors.

PMID- 9537678
TI  - In vivo apparent affinity and efficacy estimates for mu opiates in a rat tail
      withdrawal assay.
AB  - Experiments in a rat tail-withdrawal assay tested the hypothesis that the
      magnitude and pattern of antagonism of mu opiate agonists by the insurmountable
      mu opioid antagonist clocinnamox are inversely related to agonist efficacy. In
      addition, these experiments examined whether this antagonism could be quantified
      to yield apparent affinity and efficacy estimates for the pharmacological
      characterization of five opiate agonists. Etonitazene, etorphine, morphine,
      buprenorphine, and GPA 1657 produced dose-dependent increases in tail-withdrawal
      latency until 100% maximum possible effect (%MPE) was obtained. Morphine required
      a higher dose of clocinnamox for a 50% reduction in maximal antinociceptive
      effect than did buprenorphine or GPA 1657. In contrast, no dose of clocinnamox
      tested decreased the %MPE for etonitazene or etorphine. These data suggest a rank
      order of relative efficacy of etonitazene > or = etorphine > morphine > or = GPA
      1657 > or = buprenorphine. Similarly, numerical analysis of these data yielded
      the following apparent affinity and efficacy estimates: etonitazene (0.38 mg/kg,
      128); etorphine (0.68 mg/kg, 125); morphine (50 mg/kg, 38), GPA 1657 (6.6, 39);
      and buprenorphine (0.042 mg/kg, 2.2). These data illustrate that in vivo affinity
      and efficacy estimates for a number of agonists are remarkably similar across
      different methods of analysis and are useful for drug classification.

PMID- 9537679
TI  - Stress-induced cross-sensitization to cocaine: effect of adrenalectomy and
      corticosterone after short- and long-term withdrawal.
AB  - We have recently shown that adrenalectomy (ADX) in rats blocks the appearance of
      cocaine-induced sensitization when this behavioral response is tested at early
      withdrawal times (1-2 days), but not after later withdrawal from cocaine (12
      days). To determine if a similar phenomenon occurred with stress-induced
      sensitization, male Sprague-Dawley rats were given a sham ADX, ADX surgery, or
      ADX plus s.c. implanted corticosterone (CORT) pellets (CORT 12.5% pellets or CORT
      50% pellets). A fifth group was given ADX surgery, but CORT 50% pellets were
      implanted after repeated stress treatment. One week after surgery, each group was
      divided into two additional groups, naive and stress. Naive animals remained
      unhandled, while stress rats were given a variety of daily stressors administered
      twice per day for 6 consecutive days. One day after the last stress, rats were
      given a saline injection followed by a cocaine injection (15 mg/kg, i.p.) the
      next day, and locomotor activity was monitored (early withdrawal). Two weeks
      after the last stress, the locomotor responses to an additional saline and
      cocaine injection were monitored (late withdrawal). At early withdrawal, no
      significant sensitization occurred for horizontal activity, but cross
      sensitization was demonstrated for vertical activity. At late withdrawal, sham
      controls showed a stress-induced elevation in horizontal activity, with only a
      trend toward increased vertical activity. Animals given ADX surgery or ADX and
      CORT 12.5% pellets did not demonstrate sensitization to repeated stress, while
      CORT 50% pellets in ADX rats restored the sensitized horizontal response to
      cocaine challenge at late withdrawal. In contrast, stress-pretreated rats which
      were given CORT 50% pellets during the 2-week withdrawal period after the stress
      showed a marked decrease in horizontal activity in response to cocaine challenge
      at late withdrawal. The results provide evidence for a necessary role for adrenal
      hormones in long term, but not short-term, stress-induced cross-sensitization.
      Together with our previous study on the role of CORT in cocaine-induced
      sensitization, the results indicate that CORT is not the common factor mediating
      the long-term sensitization to cocaine and stress.

PMID- 9537680
TI  - Repeated methylphenidate treatment induces behavioral sensitization and decreases
      protein kinase A and dopamine-stimulated adenylyl cyclase activity in the dorsal
      striatum.
AB  - The behavioral effects of repeated methylphenidate (MPH) treatment were assessed
      in the adult rat. Protein kinase A (PKA) and adenylyl cyclase (basal and DA
      stimulated) activity in the dorsal striatum (i.e., caudate-putamen) were measured
      to determine whether MPH-induced alterations in these enzymes correlate with the
      occurrence of behavioral sensitization. In two experiments, adult rats were
      injected (i.p.) on 5 consecutive pre-exposure days with saline or MPH (5, 10, 15,
      or 20 mg/kg). Sensitization was tested after a single abstinence day, with rats
      receiving a challenge injection of MPH prior to either a 40- or 150-min testing
      session (additional control groups received saline on the test day). Immediately
      after the 40-min testing session, rats were killed and tissue from the dorsal
      striatum was dissected for later analysis of PKA and adenylyl cyclase activity.
      Results showed that repeated MPH treatment sensitized the stereotyped sniffing,
      but not the locomotor activity, of adult rats. PKA activity was significantly
      depressed in rats treated with MPH (10 or 20 mg/kg) during both the pre-exposure
      and test day phases. DA-stimulated adenylyl cyclase activity was reduced after
      chronic MPH treatment, while basal adenylyl cyclase values were enhanced. Thus,
      the present study showed that MPH was able to sensitize the stereotyped behaviors
      of adult rats, an action that corresponded with drug-induced changes in dorsal
      striatal DA signal transduction mechanisms.

PMID- 9537681
TI  - Cocaine discrimination: relationship to local anesthetics and monoamine uptake
      inhibitors in C57BL/6 mice.
AB  - Although the discriminative properties of cocaine have been examined extensively
      in rats, and to a lesser extent in other species, there are currently no reports
      on cocaine discrimination by mice. In one of our experiments, C57BL/6 (C57) mice
      acquired cocaine discrimination (10 mg/kg training dose) and exhibited dose
      responsive generalization to lower doses of the drug, which was similar to
      previous reports using rats. In addition, mazindol, a general monoamine uptake
      inhibitor similar to cocaine, and nomifensine, which is relatively specific for
      the dopamine transporter, substituted completely for cocaine, as described for
      rats. In contrast, there was little substitution evidenced by monoamine uptake
      inhibitors relatively specific for the norepinephrine transporter (nisoxetine) or
      for the serotonin transporter (fluoxetine), or by the local anesthetics procaine
      or lidocaine. In our second experiment, neither cocaine nor mazindol substituted
      for procaine in animals trained to discriminate the local anesthetic (100 mg/kg)
      although lidocaine substituted completely for the procaine cue. These experiments
      emphasize the importance of the dopamine transporter in mediating the
      discriminative stimulus effects of cocaine in C57 mice. The lack of cross
      generalization between cocaine and procaine suggests that the anesthetic
      properties of cocaine contribute little toward its discrimination by this mouse
      strain.

PMID- 9537682
TI  - Central nicotinic receptor agonists ABT-418, ABT-089, and (-)-nicotine reduce
      distractibility in adult monkeys.
AB  - Increased distractibility is associated with both Alzheimer's disease and
      attention deficit disorder. The present study examined the effects of (-)
      nicotine and the novel central nicotinic receptor (nAChR) agonists ABT-418 [(S)-3
      methyl-2-pyrrolidinyl)isoxazole] and ABT-089 [2-methyl-3-(2-(S)
      pyrrolindinylmethoxy)pyridine dihydrochloride] on the delayed recall accuracy of
      adult monkeys exposed to distracting stimuli. Unpredictable exposure to a random
      visual array produced marked decrements in recall accuracy on trials with the
      shortest delay intervals, reducing the accuracy on these trials by 23.4%.
      Intramuscular (i.m.) administration of (-)-nicotine, in doses of 5.4-43.3
      nmol/kg, attenuated the effect of the distractor, but did not completely prevent
      it. Both ABT-418 (2.0-16.2 nmol/kg, i.m.) and ABT-089 (16.4-32.8 nmol/kg, i.m.)
      prevented distractibility, producing increases of 7.5-25.0% in accuracy on trials
      disrupted by distractor exposure. Further, both compounds also improved accuracy
      on trials during which distractors were not presented, an effect which was not
      observed after (-)-nicotine administration. Nicotinic-mediated side effects were
      not observed following administration of any compound. Thus, nAChR stimulation
      reduces distractibility in adult monkeys and may, therefore, represent a target
      for the pharmacologic treatment of disorders associated with susceptibility to
      distraction. ABT-418 and ABT-089 appear to be particularly useful in this regard,
      a likely result of their selective agonist activity at nAChRs expressed in the
      brain.

PMID- 9537683
TI  - Dopaminergic activity and the discriminative stimulus effects of mu opioids in
      pigeons: importance of training dose and attenuation by the D3 agonist (+/-)-7-OH
      DPAT.
AB  - The present investigation examined the effects of several dopaminergic compounds
      in pigeons trained to discriminate either a 0.1 (low) or 5.6 (high) mg/kg dose of
      the mu opioid butorphanol from saline. Various dopamine (DA) re-uptake
      inhibitors, releasers, a D1 agonist, a D2 agonist and a D3 agonist engendered
      partial substitution (50-79% butorphanol responding) for the butorphanol stimulus
      in the low-dose group. In the high-dose group, with a few exceptions, these
      compounds produced predominately saline responding. In the low-dose group, the
      opioid antagonist naloxone antagonized the stimulus effects produced by
      butorphanol, but failed to attenuate the butorphanol-like discriminative stimulus
      effects produced by the DA re-uptake inhibitors mazindol and cocaine. The D1
      antagonist (+)-SCH 23390 and the D2 antagonist raclopride failed to attenuate the
      stimulus effects produced by either the low or high training dose of butorphanol.
      Doses of mazindol and cocaine that engendered between 16% and 70% butorphanol
      responding failed to alter the butorphanol dose-effect curve in either the low-
      or high-dose group, indicating a less than additive interaction. In the high-dose
      group, the D3 agonist (+/-)-7-hydroxy-dipropylaminotetralin [(+/-)-7-OH-DPAT]
      attenuated butorphanol's stimulus effects in a dose-dependent manner along with
      the butorphanol-like stimulus effects produced by nalbuphine and morphine. The
      present findings indicate that direct and indirect DA agonists share similar
      stimulus effects with a low but not high training dose of butorphanol, and in the
      high-training dose group, activation of the D3 receptor by (+/-)-7-OHDPAT results
      in the attenuation of the discriminative stimulus effects of mu opioids.

PMID- 9537684
TI  - Motivational effects of compounding discriminative stimuli associated with food
      and cocaine.
AB  - In previous experiments, the compounding of two discriminative stimuli associated
      with the same reinforcer increased rats' responding approximately three-fold,
      regardless of whether the reinforcer was food, water, cocaine, or shock
      avoidance. Compounding a discriminative stimulus associated with food with one
      associated with water increased responding two-fold. In the present experiment,
      compounding a discriminative stimulus associated with food with one associated
      with cocaine increased responding two-fold. These results support the hypothesis
      that 1) the effects of stimuli associated with reinforcers from the same
      incentive class (appetitive or aversive) are mutually enhancing, and 2) the
      combined effects of stimuli associated with two different reinforcers from within
      the same class are not as strong as those of two stimuli associated with the same
      reinforcer. These results also suggest that discriminative stimuli associated
      with non-drug reinforcers may increase the motivation to self-administer cocaine
      when encountered in combination with drug-related stimuli.

PMID- 9537685
TI  - SKF 38393 enhances odor detection performance.
AB  - The purpose of this study was to determine the influence of the D1-selective
      partial agonist SKF 38393 on the odor detection performance of rats using high
      precision olfactometry and a go/no-go operant task. Previous studies have found
      that the D2 receptor partial agonist quinpirole decreases such performance, but
      the influences of D1 receptor activation are unknown. In experiment 1, such
      detection performance to the odorant ethyl acetate was enhanced by SKF 38393,
      relative to saline, in male rats at 7.5 and 10.0 mg/kg i.p. dose levels, but not
      at the lower doses of 1.0, 2.5, and 5.0 mg/kg. In experiment 2, this enhancement
      was replicated at the 7.5 and 10.0 mg/kg doses and was shown to occur at the 12.5
      mg/kg dose as well. In experiment 3, similar enhancement was shown for the
      odorant eugenol in female rats at the 7.5, 10.0 and 12.5 mg/kg doses, suggesting
      this effect is neither sex-specific nor confined to the odorant ethyl acetate. In
      experiment 4, a 0.025 mg/kg dose of the D1 receptor antagonist SCH 23390
      depressed the enhancement produced to ethyl acetate by 7.5 mg/kg SKF 38393 to
      control levels. Overall, these data demonstrate that, in contrast to quinpirole,
      SKF 38393 improves odor detection performance in the rat and that this phenomenon
      can be attenuated by the D1 receptor blocker SCH 23390.

PMID- 9537686
TI  - Acquisition of nicotine self-administration in rats: the effects of dose, feeding
      schedule, and drug contingency.
AB  - The studies presented here were designed to further clarify the nature of
      nicotine self-administration (SA) based on a limited access model in which rats
      are food restricted, receive operant training using food reinforcement, and are
      then tested in daily 1-h drug sessions. We examined the effects of dose, feeding
      schedule, and contingency of drug delivery on acquisition of nicotine SA. Two
      doses of nicotine bitartrate, 0.03 and 0.06 mg/kg per infusion (free base),
      supported the transition from food-reinforced to drug-reinforced responding,
      although the pattern of behavior differed between these doses. In contrast, 0.01
      mg/kg per infusion failed to maintain nicotine SA. In a second study, animals
      were divided into three groups according to feeding schedule. Rats that were both
      weight restricted and food deprived showed the highest level of SA behavior,
      although neither food deprivation nor weight restriction was necessary to
      establish SA. In the third experiment, rats that were switched from food to
      nicotine as the response-dependent reinforcer maintained higher response rates
      throughout a 9-day period than animals switched to response-independent (i.e.,
      yoked) nicotine which showed minimal responding after day 1. Furthermore, the
      differences between self-administering and yoked animals emerged during the first
      session, suggesting that nicotine may serve as a reinforcer during the first drug
      exposure in naive animals. These results indicate that acquisition of nicotine SA
      can be influenced by both dose of nicotine and feeding schedule and that, in
      animals previously trained on a food-reinforced operant, active lever pressing is
      maintained only when nicotine delivery is contingent upon responding.

PMID- 9537687
TI  - Acute tolerance to the ataxic effects of ethanol in short-sleep (SS) and long
      sleep (LS) mice.
AB  - The objective of this series of studies was to examine the relationship between
      alcohol sensitivity and the development of very rapid acute tolerance to alcohol
      in mice. In order to measure acute tolerance to alcohol, a behavioral test was
      developed using a rotorod. In the first study, mice selectively bred for
      resistance (short sleep, SS) or sensitivity (long sleep, LS) to the acute
      hypnotic effects of ethanol were used, as well as mice from the base population
      (heterogeneous stock, HS). Mice were trained to run on the rotorod at a speed of
      14 rpm to a criterion of 200 s, in four daily training sessions. On the test day,
      baseline measurements of rotorod performance were taken and mice were injected
      i.p. with alcohol in doses from 0 to 2.5 g/kg. Animals were tested at 1-min
      intervals for the first 5 min following injection, then at 5-min intervals for a
      total of 30 min. The results demonstrated that SS and HS mice developed tolerance
      within 10 min following the alcohol injections. LS mice did develop some acute
      tolerance, but at a much slower rate than the SS or HS mice. In the second study,
      the effects of intoxicated practice on the rates of acute tolerance development
      were examined in the SS, HS and LS mice at a dose of 2.0 g/kg alcohol. A total of
      ten groups of each strain were given a different number of practice trials
      (ranging from one to ten) on the rotorod prior to a final test session at 30 min
      post-injection. The results provide evidence that SS and HS mice are capable of
      developing acute tolerance independent of practice. That is, the group of animals
      injected at 0 time and tested ten times up to 30 min were no better at the 30-min
      time point than the group injected at 0 time and tested only once at 30 min. On
      the other hand, the LS mice showed a modest practice effect, developing
      additional tolerance to the ataxic effects of alcohol with increasing intoxicated
      practice. Overall, these studies demonstrated that mice can develop acute
      tolerance within minutes following alcohol exposure, and that this ability is
      correlated with the initial sensitivity to alcohol.

PMID- 9537688
TI  - Automated image analysis for bladder cancer.
AB  - The genetic and epigenetic changes that occur during cancer development result in
      apparent morphological changes. Light microscopic image analysis provides
      objective assessment of cellular and nuclear morphology. The complexity of
      changes reflects the basic nature of dedifferentitation: a multi-hit process.
      Image analysis methods proved valuable for the assessment of malignancy in
      bladder cancer. Clinically applicable systems have been developed to diagnose
      urothelial cell cancer and predict prognosis. What is the place of these systems
      in daily practice?

PMID- 9537689
TI  - Sexual functions in patients with benign prostatic hyperplasia before and after
      transurethral resection of the prostate.
AB  - The purpose of this prospective study was to evaluate the sexual function of
      patients with benign prostatic hyperplasia (BPH) before and after transurethral
      resection of the prostate (TURP). The sexual functions of 155 patients with BPH
      were evaluated before TURP and 6 and 12 months afterwards. The mean age of the
      patients was 69 years (range 49-86 years). The only significant change in sexual
      function after TURP was improvement in early morning erections (P < 0.01). Sixty
      eight per cent of the patients were satisfied with their sex life before TURP,
      69% after 6 months and 67% after 12 months. The corresponding percentages of
      patients satisfied with their libido were 60%, 59% and 54%. Only 26% of the
      patients had completely satisfactory erections before TURP, while 22% had them 6
      months later and 24% 12 months later. The proportion of fully impotent patients
      was 11% before the procedure, 13% after 6 months and 16% after 12 months. In 84%
      of the patients ejaculation was retrograde 6 months and 12 months after TURP. We
      conclude that TURP does not affect the sexual function of patients with BPH, with
      the exception of retrograde ejaculation.

PMID- 9537690
TI  - Is gamma-linolenic acid an effective intravesical agent for superficial bladder
      cancer? In vitro cytotoxicity and in vivo tolerance studies.
AB  - The essential fatty acid gamma-linolenic acid (GLA) is an effective cytotoxic
      agent when applied topically and for prolonged periods to tumour cells. Topical
      application, by intravesical therapy, is firmly established in the treatment of
      superficial bladder cancer. However, this form of therapy is limited to a maximum
      duration of 2 h. At such a short drug exposure time, does GLA retain its
      cytotoxicity? We have examined this question by exposing the superficial bladder
      cancer cell lines MGH-U1 and RT112 to meglumine-GLA (MeGLA) for time intervals
      ranging from 30 min to 2 h, at drug concentrations ranging from 1000 to 1.95
      microg/ml. The MTT viable biomass assay was used to assess cell kill. Greater
      than 90% inhibition was observed at a concentration of 125 microg/ml (IC > 90),
      at 2 h drug exposure. At shorter drug exposure times, higher drug concentrations
      were needed to induce the same effect. At 1 h drug exposure, the IC > 90 was
      recorded at 500 microg/ml. In vivo intravesical tolerance studies were conducted
      in rats. Rats exposed to 2.5 mg/ml MeGLA intravesically for 2 h or less remained
      well and bladder histology showed minimal changes. This study confirms that GLA
      retains its cytotoxicity at short drug exposure times and is well tolerated by
      normal bladder mucosa in vivo. Bladder mucosa tolerated > 10x the concentration
      required for the IC > 90 in vitro. MeGLA is therefore a feasible intravesical
      agent for superficial bladder cancer.

PMID- 9537691
TI  - Involvement of Fas in the apoptosis of mouse germ cells induced by experimental
      cryptorchidism.
AB  - The role of Fas in the apoptosis of testicular germ cells was investigated in
      BALB/c mice and Fas-deficient lpr/lpr mice. Spontaneous apoptosis of germ cells
      was observed in the testes of 40-day-old BALB/c mice, and experimentally induced
      cryptorchidism increased this apoptosis to such an extent that there was a
      decrease in the weight of the testis. Flow cytometry and immunohistochemistry
      using a Fas-specific monoclonal antibody demonstrated expression of Fas on germ
      cells including spermatogonia, spermatocytes, and spermatids. Furthermore,
      analysis by flow cytometry suggested that Fas expression on germ cells was
      increased following cryptorchidism. However, spontaneous and cryptorchidism
      induced apoptosis of germ cells were also observed in 40-day-old Fas-deficient
      lpr/lpr mice. Moreover, testis weight also decreased following cryptorchidism in
      the mutant mice. The present results may indicate that the expression of Fas on
      germ cells does not correlate with spontaneous apoptosis or apoptosis induced by
      cryptorchidism. However, on the contrary, this study shows that Fas are partly
      involved in cryptorchidism-induced apoptosis, because the decrease in testis
      weight of lpr/lpr mice was less than that in BALB/c mice.

PMID- 9537693
TI  - Telomerase activity in adrenal cortical tumors and pheochromocytomas with
      reference to clinicopathologic features.
AB  - Telomeres consist of short repeated sequences that are shortened on continuous
      cell proliferations and synthesized by telomerase, an RNA-dependent DNA
      polymerase. Recent molecular studies have reported that telomerase is activated
      in most human cancers, whereas it is not detected in most somatic cells. These
      findings indicate that the positive telomerase activity is closely related to the
      malignant potential of human tumors. In several types of human tumors, including
      adrenal cortical tumors and pheochromocytomas, it is very difficult to predict
      the malignant potential using conventional histopathologic examination. To
      determine whether telomerase activity is useful as a diagnostic marker, we
      examined telomerase activity in adrenal cortical tumors and pheochromocytomas
      with special reference to their clinicopathologic features. Using a highly
      sensitive polymerase chain reaction (PCR)-based detection method, telomerase
      activity was demonstrated in one of 13 adrenal cortical tumors and two of seven
      pheochromocytomas, whereas all seven normal portions of adrenal gland failed to
      showed any telomerase activity. Although none of the tumors examined in this
      study was associated with metastasis, these three telomerase-positive tumors were
      accompanied by clinicopathologic features suggesting malignant potential.
      Telomerase activity might be a potential marker for estimating the biologic
      characteristics of adrenal cortical tumors and pheochromocytomas.

PMID- 9537692
TI  - Immunolocalization of anti-placental alkaline phosphatase monoclonal antibody in
      mice with testicular tumors and lymph node metastasis.
AB  - To evaluate the ability of an anti-placental alkaline phosphatase (PLAP)
      monoclonal antibody (MAb) to localize to PLAP-expressing tumors, we established a
      model of testicular tumor with metastasis to lymph nodes and liver in severe
      combined immunodeficient (SCID) mice. 131I-labeled or 125I-labeled MAb was
      simultaneously administered via the intravenous or lymphatic route, respectively.
      Preferential accumulation of MAb in PLAP-expressing tumors at primary as well as
      metastatic sites was demonstrated. The percentage of the injected dose of MAb
      found in the tumor was generally higher when MAb was administered intravenously.
      Identical tumor/blood ratios were found with the two routes of administration.
      These data suggest that intravenous administration of a radiolabeled MAb is
      superior to lymphatic administration for tumor imaging and radioimmunotherapy.

PMID- 9537694
TI  - Influence of cytokines and growth factors on matrix metalloproteinase-2
      production and invasion of human renal cancer.
AB  - This study evaluated the influence of cytokines and growth factors on the
      production of matrix metalloproteinase-2 (MMP-2, 72-kDa type IV collagenase,
      gelatinase A) and invasion of the human renal cell carcinoma (HRCC) cell line KG
      2. The cells were treated with cytokines and growth factors, and the gelatiolytic
      activity and in vitro invasion were examined. Basic fibroblast growth factor
      (bFGF) stimulated MMP-2 production by KG-2 cells to 2.0-, 4.84- and 4.53-fold
      that of the untreated group at 0.1, 1.0 and 10 ng/ml, respectively. Transforming
      growth factor-beta1 (TGF-beta1) at very low concentrations of 10 pg/ml and 100
      pg/ml stimulated enzyme production in KG-2 cells by 1.74- and 2.83-fold,
      respectively. In contrast, interferon-gamma (IFN-gamma) decreased MMP-2
      production by KG-2 cells at 10 and 100 U/ml to 69% and 41% of the level in the
      untreated group, respectively. At those concentrations, IFN-gamma did not cause
      cytostasis in KG-2 cells. Moreover, bFGF and TGF-beta1 (low concentrations)
      stimulated in vitro invasion of KG-2 cells, but IFN-gamma decreased the invasive
      activity, which was well correlated with the levels of MMP-2. However, the
      expression of MMP-2 mRNA of KG-2 cells treated with 10 ng/ml bFGF, 100 pg/ml TGF
      beta1 and 100 U/ml IFN-gamma was shown to be 3.8-, 3.4- and 0.7-fold,
      respectively, those in untreated groups. Thus the production of MMP-2 in HRCC was
      influenced by cytokines and growth factors, and MMP-2 plays an important role in
      the invasion and metastasis of certain types of HRCC.

PMID- 9537695
TI  - Functional response of cavernosal tissue to distension.
AB  - We studied rabbit isolated erectile tissue responses to changes in preload and to
      active tension development with norepinephrine. The effects of antagonists of
      endothelin-1, prostaglandins E2 and F2alpha and of nitric oxide were also tested
      on normal and de-endothelialized preparations. Tissue distension was found to
      elicit spontaneous rhythmic contractions. Increase in preload diminished the
      latency of the spontaneous activity and augmented the developed force. Active
      tension development and the inhibitor of the Na+,K+ pump, ouabain, opposed the
      spontaneous activity. A marked reduction in the resting tension with abolition of
      the spontaneous activity was observed on normal, but not on de-endothelialized
      tissues, following the addition of the specific prostaglandin E2 and F2alpha
      receptor antagonist, SC-19220. At 3 x 10(-4) M, the highest concentration used,
      the endothelin-A receptor antagonist BQ-123 failed to change the pattern of the
      spontaneous activity and the resting tension of normal tissues. The nitric oxide
      synthesis inhibitor, L-NAME, did not produce reliable effects. These findings
      point to a causal relation between cavernosal tissue distension and phasic and
      tonic contractions. Phasic contractions appear to be elicited by smooth muscle
      cells through the enzyme Na+,K+-ATPase. Increase in the resting tone could be
      mediated, at least in part, by the endothelium, through the release of
      prostaglandins E2 and/or F2alpha but not of endothelins. We discuss the
      hypothesis that, in cavernosal tissue, mechanotransduction of distension to
      contractile responses is an important determinant of detumescence.

PMID- 9537696
TI  - Effects of smoking on testicular function and fertilizing potential in rats.
AB  - We evaluated the effects of smoking on testicular function and fertilizing
      potential in rats. Twenty rats (group A) were exposed to the smoke of 20
      cigarettes for 1 h per day. Ten rats (group B) were exposed to the smoke of 40
      incense sticks for 1 h per day, and an additional 10 rats served as a control
      group (group C). After 10 weeks of daily exposure, serum levels of nicotine and
      cotinine were assessed, and a mating test was conducted. Five days later, serum
      concentrations of testosterone before and after human chorionic gonadotropin
      (hCG) stimulation, gonadotropins, and epididymal sperm content and motility were
      evaluated. In addition, in vitro fertilization was carried out. Nicotine and
      cotinine were detected in group A, but not in groups B and C. Basal serum
      testosterone and gonadotropin concentrations did not differ significantly among
      the three groups, but the testosterone response to hCG stimulation was
      significantly lower in group A than in groups B and C. Group A showed significant
      reductions in epididymal sperm content and motility, and in fertility in vivo and
      in vitro. These findings suggest that smoking leads to a secretory dysfunction of
      the Leydig cells, and also a deficiency in sperm maturation and spermatogenesis.
      In addition, smoking has a detrimental effect on sperm fertilizing potentials in
      vivo and in vitro.

PMID- 9537697
TI  - N-acetylneuraminic acids (nana): a potential key in renal calculogenesis.
AB  - N-Acetylneuraminic acids (NANA) promote binding of calcium ions to macromolecules
      and cells, increase the intrinsic viscosity of glycoproteins and facilitate gel
      formation in water. Since these properties are crucial in urinary calculogenesis,
      we evaluated NANA levels in urine and serum as well as their expression in kidney
      tissues. Using a modified thiobarbituric acid assay, the evaluation of free and
      bound NANA in 24-h urine samples revealed a ratio of 1.87 in 33 non-stone-formers
      but a reversed ratio of 0.84 in 41 recurrent calcium oxalate stone-formers. Time
      kinetics revealed a gradual rise in NANA expression until 48 h of culture and a
      significantly higher release into supernatants of papillary renal epithelial
      cells (REC) when compared with cortical REC. To examine NANA distribution in
      kidney tissues, paraffin-embedded biopsies from five normal and six stone-forming
      kidneys were labeled with the biotinylated NANA-specific lectins Maackia
      amurensis (MAA) and Sambucus nigra (SNA). Immunohistochemistry revealed intense
      luminal MAA reactivity of distal tubular REC and collecting ducts in 96.7% and
      91.5% of normal and stone-forming kidneys respectively. By contrast, there was a
      marked difference between normal and stone-forming kidneys for SNA reactivity
      (17.7% vs 95%) at the same locations. Finally, the glycocalyx of recurrent stone
      formers showed altered sialylglycoside linkages [alpha(2,6) instead of
      alpha(2,3)] that may indicate an altered REC function. Given the calcium-binding
      potential of NANA, their increased local concentration within the glycocalyx
      layer in the distal nephron may either initiate stone formation or facilitate
      attachment of microcrystals to REC.

PMID- 9537698
TI  - A stable animal model of diet-induced calcium oxalate crystalluria.
AB  - Twenty male Wistar rats, weighing 150 g, were placed in metabolic cages on a 30%
      sucrose diet for 7 days, before allocation to two groups: a control group (n = 5)
      and a lactose group (n = 15). They received respectively a 30% sucrose diet or a
      30% lactose diet for 8 weeks, each containing 0.67% calcium and 0.38% phosphorus.
      After 4 (T1) and 8 (T2) weeks, the serum calcium (Ca) and citrate levels were
      significantly (P < 0.01) higher in rats fed the lactose diet. Serum alkaline
      phosphatase activity was increased in the lactose group (P < 0.01) at T1 and T2.
      The lactose-rich diet induced an increase in urinary Ca excretion at T1 and T2;
      citrate excretion was only enhanced at T2 (P < 0.001). No difference between the
      two groups was observed in urinary oxalate (Ox) excretion or creatinine
      clearance. Crystalluria analysis revealed a marked number (>300/mm3 at T1 and T2)
      of calcium oxalate dihydrate crystals (COD) in rats fed the lactose-rich diet,
      whereas no COD crystals were observed in sucrose-fed control rats at any time
      point. The formation of COD crystals in lactose-fed rats was related to an
      increase in calcium oxalate (CaOx) product (pCaOx), which was respectively 12.6
      vs 3.9 at T1 and 10.5 vs 1.8 at T2, and an increase in CaOx ratio (Ca/Ox), which
      was 99.1 vs 7.5 and 67.5 vs 18.5 at T1 and T2, respectively. The high pCaOx and
      Ca/Ox ratios in the lactose group were due to hypercalciuria, in agreement with
      the number and the type of crystals. The present experimental model confirms that
      the ingestion of a 30% lactose diet increases urinary Ca excretion without
      changing urinary Ox excretion and shows for the first time that it induces a
      stable and marked crystalluria composed of COD. Such a non-nephrotoxic and stable
      model is of interest for the study of CaOx crystal formation secondary to
      hypercalciuria, and thus afterwards eventually for CaOx nephrolithiasis.

PMID- 9537699
TI  - The effects of the calcium-restricted diet of urolithiasis patients with
      absorptive hypercalciuria type II on risk factors for kidney stones and
      osteopenia.
AB  - The calcium (Ca)-restricted diet of urolithiasis patients with absorptive
      hypercalciuria type II may decrease Ca excretion but increase biochemical markers
      of risk for osteopenia. We randomly allocated 25 patients from six hospitals into
      an experimental group (Ca restriction to 500 mg/day, oxalate-rich products
      discouraged and normalization of animal protein and sodium) and a control group
      (no restrictions) for one month. The urinary Ca excretion did not decrease
      significantly, but the oxalate excretion decreased, although not significantly.
      The hydroxyproline:creatinine ratio in fasting urine seemed to increase and the
      calcium:creatinine ratio to decrease. The deoxypyridinoline:creatinine ratio in
      fasting urine did not change. We conclude that our Ca-restricted diet, which is
      lower in Ca, animal protein and table salt due to the omission of dairy products,
      may be of benefit for absorptive hypercalciuria type II patients without
      enhancing the risk for osteopenia. However, a long-term clinical trial is
      required.

PMID- 9537701
TI  - Chemotherapy in cancer of the liver, pancreas and bile ducts. Consensus statement
      of a workshop at The Swedish Society for Upper Abdominal Surgery sponsored by the
      Swedish Cancer Society.

PMID- 9537700
TI  - Effect of castration and finasteride on urinary oxalate excretion in male rats.
AB  - We investigated the effects of castration and finasteride administration on
      urinary oxalate (Ox) excretion in a rat ethylene glycol (EG) model of
      urolithiasis. Male adult SD rats were divided into six groups. Group 1 were
      normal, untreated rats. The other five groups, all treated with 0.75% EG for 4
      weeks; were as follows: group 2, non-castrated (intact) rats; group 3, castrated
      rats; group 4, castrated rats with a 4-cm testosterone implant; group 5, intact
      rats treated with high-dose finasteride (7.5 mg%); and group 6, intact rats
      treated with low-dose finasteride (0.75 mg%). Urinary Ox excretion increased 12.8
      fold after 4 weeks of EG treatment (group 2 vs group 1). Both castration (group
      3) and finasteride administration (groups 5 and 6) significantly decreased
      urinary Ox excretion compared with intact rats (group 2). We conclude that
      dihydrotestosterone is partially responsible for the exaggerated hyperoxaluria
      observed in the rat EG model of urolithiasis.

PMID- 9537702
TI  - Use of desmopressin to prevent bleeding in surgery.

PMID- 9537703
TI  - Forced air warming and intraoperative hypothermia.
AB  - OBJECTIVES: To compare a forced air warming system with passive measures to avoid
      perioperative hypothermia. DESIGN: Prospective open study. SETTING: University
      hospital, Sweden. SUBJECTS: 28 Patients scheduled for extensive thoracoabdominal
      operations under standard combined general and regional anaesthesia. MAIN OUTCOME
      MEASURES: Temperature measured before, repeatedly under anaesthesia and during
      the operation for up to three hours, and then up to eight hours postoperatively.
      RESULTS: Three patients were excluded. In the 12 patients who had forced air
      warming, temperature was preserved, and ranged from a mean (SD) of 36.8 (0.7)
      degrees C, (95% confidence interval (CI) 36.4 to 37.2) at the start to 36.9 (0.8)
      degrees C, (95% CI 36.5 to 37.3) after 3 hours. In patients who had conservative
      passive heat preservation techniques the mean temperature fell significantly
      perioperatively, from 36.8 (0.6) degrees C (95% CI 36.5 to 37.1) at the start to
      35.1 (0.5) degrees C, (95% CI 34.9 to 35.3), after three hours of anaesthesia and
      surgery. This was a significant fall compared with the temperature in the study
      group (p < 0.001). CONCLUSION: Forced air warming intraoperatively can preserve
      normothermia during extensive thoracoabdominal operations.

PMID- 9537704
TI  - Abdominal stab wounds: the role of selective management.
AB  - OBJECTIVE: To investigate the role of a selective approach to the operative
      treatment of abdominal stab wounds. DESIGN: Retrospective study. SETTING:
      University hospital, Turkey. SUBJECTS: 387 patients with stab wounds of the
      abdomen, who presented between January 1992 and January 1995. INTERVENTIONS:
      After local exploration of the wound, 200 patients in whom the wound had
      penetrated the peritoneum, underwent diagnostic peritoneal lavage. The lavage
      fluid was examined for white cells, red cells, and amylase and alkaline
      phosphatase activity. The severity of the injury was evaluated with the
      penetrating abdominal trauma index (PATI). MAIN OUTCOME MEASURES: Morbidity and
      mortality. RESULTS: The main complications were wound infection (n=15), wound
      dehiscence (n=5), pneumonia (n=3) and renal failure (n=1). Five patients died.
      The median hospital stay was 6.1 days when patients were operated on, and 1.5
      days when they were not. CONCLUSIONS: We managed to minimise the number of
      negative and unnecessary laparotomies. We emphasise that the selective approach
      may easily be applied in teaching hospitals.

PMID- 9537705
TI  - Effectiveness and limits of preoperative imaging studies for the localisation of
      pheochromocytomas and paragangliomas: a review of 282 cases. French Association
      of Surgery (AFC), and The French Association of Endocrine Surgeons (AFCE).
AB  - OBJECTIVE: To find out the optimal strategy for the preoperative location of
      pheochromocytomas and paragangliomas. DESIGN: Retrospective study. PATIENTS: 282
      patients operated on for histologically confirmed pheochromocytoma in France
      between 1980 and 1991, the past decade. MAIN OUTCOME MEASURES: The results of
      imaging procedures, i.e. computed tomography (CT), (131)I meta
      iodobenzylguanidine scintigraphy (MIBG) and magnetic resonance imaging (MRI) were
      reviewed. RESULTS: Pheochromocytomas were sporadic in 206 (73%). They were
      unilateral in 189 (67%), bilateral in 54 (19%) and extra-adrenal in 39 (14%).
      Overall sensitivity of the studies was 89% for CT, 98% for MRI, and 81% for
      (131)I-MIBG. In unilateral adrenal lesions sensitivity were 100% for CT and MRI,
      and 88% for (131)I-MIBG; in bilateral lesions 66% for CT, 100% for MRI, and 62%
      for (131)I-MIBG; in extra-adrenal lesions 64% for CT, 88% for MRI, and 64% for
      (131)I-MIBG. CONCLUSION: The accuracy with which pheochromocytomas and
      paragangliomas can be visualized questions nowadays the routine use of abdominal
      approach. In selected cases of sporadic unilateral chromaffin tumours, a
      posterior, lateral, or even laparoscopic approach should be considered.

PMID- 9537706
TI  - Ruptured abdominal aortic aneurysm: initial misdiagnosis and the effect on
      treatment.
AB  - OBJECTIVE: To evaluate the incidence of misdiagnosis in ruptured abdominal aortic
      aneurysm and its effect on treatment and outcome. DESIGN: Retrospective study.
      SETTING: Teaching hospital, The Netherlands. SUBJECTS: 97 consecutive patients
      admitted with ruptured abdominal aortic aneurysm during the 5-year period, 1
      January 1989--31 December 1993. MAIN OUTCOME MEASURES: Initial diagnosis,
      interval between onset of symptoms and admission, and mortality. RESULTS: 38
      Patients (43%) presented with symptoms of their aneurysm exceeding nine hours
      prior to admission (range 10 hours to 14 days, median 2 days). Fifty patients
      (60%) were initially misdiagnosed by the referring practitioner. Ultrasonography
      was consistent with rupture in only 36/70 (51%). 52 Patients died (54%),
      (operative mortality 45 (46%)), and was not affected by delay in diagnosis or
      treatment. CONCLUSIONS: Although delay in diagnosis or treatment did not seem to
      affect mortality, improved awareness of non-specific presentations of (imminent)
      rupture will result in fewer misdiagnoses and earlier treatment. A group of
      patients will undoubtedly benefit from this as they can be operated on at a stage
      when expected mortality is lower.

PMID- 9537707
TI  - Surgical treatment of chronic critical leg ischaemia. A five-year follow-up of
      survival, mobility, and treatment level.
AB  - OBJECTIVE: To evaluate mobility and care level required after amputation and
      arterial reconstruction for chronic critical leg ischaemia. DESIGN: A 5 year
      follow up study in three hospitals serving a defined population. SETTING: One
      regional and two district hospitals, Finland. PATIENTS: 117 Consecutive patients.
      OUTCOME MEASURES: Survival, amputations, mobility, and care level required. MAIN
      RESULTS: 66 Primary reconstructions, 51 primary and 35 later major amputations
      were done. Preoperatively 27 (53%) of the patients who underwent a primary
      amputation were in permanent institutional care. Of 86 patients who were living
      outside an institution, 62 (72%) had a reconstruction. One and five year
      mortality were 43% and 84% after amputation, and 20% and 57% after
      reconstruction, respectively. Of the patients who had had an amputation 10% were
      able to walk and 25% could manage to live outside an institution. Mobility and
      treatment level after primary and secondary amputations were similar. Forty seven
      (71%) of the patients who had had a reconstruction did not have an amputation.
      All patients whose reconstructions were successful preserved their walking
      ability and independent living. CONCLUSION: To maintain mobility and an
      independent living in patients with chronic critical leg ischaemia it is
      necessary to do a reconstruction that can salvage the leg. In old,
      institutionalised patients chronic critical leg ischaemia is often the harbinger
      of approaching death and then amputation is the only possible solution.

PMID- 9537708
TI  - Reoperation as surrogate endpoint in hernia surgery. A three year follow-up of
      1565 herniorrhaphies.
AB  - OBJECTIVE: Analysis of reoperation and recurrence rates three years after repair
      of groin hernias. DESIGN: Prospective audit by questionnaire and selective follow
      up. SETTING: Eight Swedish hospitals. SUBJECTS: All groin hernia operations done
      during 1992 on patients between the ages of 15 and 80 years. MAIN OUTCOME
      MEASURES: Postoperative complications, reoperation for recurrence, and
      recurrence. RESULTS: During 1992, 1565 hernia operations were done. The
      postoperative complication rate was 8% (125/1565). At 36 months postoperatively
      108 recurrences had already been reoperated on, six patients with recurrences
      were on the waiting list for reoperation and a further 36 recurrences had been
      detected at follow-up. The interhospital variation in recurrence rate ranged from
      3% to 20%. Postoperative complications, recurrent hernia, direct hernia and
      hospital catchment area over 100000 inhabitants were all factors associated with
      an increased relative risk of recurrence. CONCLUSIONS: The recurrence rate
      exceeded the reoperation rate for recurrence by almost 40% which should be taken
      into account if the reoperation rate is used as the endpoint after repairs of
      groin hernia. An audit scheme, based on prospective recording, reoperation rate,
      and (periodic) calculation of the recurrence rate may be used to identify risk
      factors for recurrence and areas in need of improvement.

PMID- 9537709
TI  - Small bowel volvulus: a common cause of mechanical intestinal obstruction in our
      region.
AB  - OBJECTIVE: To find out the incidence and causes of small bowel volvulus in our
      region, and to analyse the results of our management. DESIGN: Retrospective
      study. SETTING: Teaching hospital, Turkey. SUBJECTS: 38 Patients who had had no
      previous abdominal operations who were operated on for mechanical intestinal
      obstruction caused by small bowel volvulus. MAIN OUTCOME MEASURES: Incidence of
      small bowel volvulus, details of patients, treatments, complications, and
      outcome. RESULTS: Small bowel volvulus constituted 8%(38/466) of all cases of
      mechanical intestinal obstruction and 13%(38/292) of small bowel obstruction.
      Volvulus was primary in 18 (47%), and secondary in 20 (53%) patients. 33 Patients
      (87%) were male. The mean age of the whole group was 30 years, 42 and 19 in
      patients with primary and secondary volvulus, respectively (p=0.0005). The
      incidence of small bowel volvulus was 19%(27/143) in patients under 40 years, and
      7%(11/149) in those over 40 years of age (p=0.005). Sixty percent of patients
      with secondary volvulus (12/20) were under 20 years of age compared with 17% of
      those with primary volvulus (3/18; p=0.009). The causes of secondary volvulus
      were Meckel's diverticulum in 14 patients (70%), and malrotation and ileosigmoid
      knotting in 3 patients each (15%). Segments of bowel were gangrenous in 12
      patients (32%). Treatment was by simple untwisting in patients with viable
      segments of gut, or with resection of gangrenous segments and primary small bowel
      anastomosis. One patient died postoperatively of septic shock. CONCLUSIONS: Small
      bowel volvulus is a common form of intestinal obstruction in our region. It
      carries a high risk of gangrene of twisted segments of bowel. Fortunately
      perforation of small bowel is uncommon, and resection and primary anastomosis is
      a safe procedure in cases of necrosis. Today the outcome of such patients is
      satisfactory. Early and proper management is essential for a good outcome.

PMID- 9537710
TI  - Comparative study of air coagulation, fibrin sealant, and suture in experimental
      liver injury.
AB  - OBJECTIVE: To test the effects of hot air coagulation, fibrin sealant, and
      horizontal mattress sutures on haemostasis and regeneration in experimental
      hepatectomy. DESIGN: Randomised laboratory experiment. SETTING: Teaching
      hospital, Spain. MATERIAL: 200 rats divided into four groups (three experimental
      [n=60 in each] and one control [n=20]). INTERVENTIONS: Hepatic injuries were
      repaired by suture, coagulation, or fibrin sealant in the three experimental
      groups. The control group was used only to supply baseline blood samples. 10
      animals in each experimental group were killed at 3, 5, 10, 25, 40, and 60 days.
      MAIN OUTCOME MEASURES: Time taken to achieve haemostasis, and histopathological
      scores of healing. RESULTS: Mattress sutures took mean (SEM) of 346 (7) seconds
      to control the haemorrhage and allow the liver to regain its shape and 4 rats
      developed abscesses (7%). Fibrin sealant achieved haemostasis immediately and the
      liver regained its shape in 58 (2) seconds; 2 rats (3%) developed abscesses. Hot
      air coagulation achieved haemostasis in 27 (1) seconds and there were no
      abscesses. CONCLUSION: Fibrin sealant was the best technique because it achieved
      immediate haemostasis and speedy regeneration. However, hot air coagulation is a
      useful and cheaper alternative.

PMID- 9537711
TI  - Concentrations of parathyroid hormone in functioning and non-functioning
      parathyroid cysts.

PMID- 9537712
TI  - Near-total aortic replacement for acute type A dissection in a patient with
      Marfan syndrome.

PMID- 9537713
TI  - Potential for recurrence of an inguinal hernia after open repair with a preshaped
      mesh.

PMID- 9537714
TI  - Chronic idiopathic anal pain.

PMID- 9537715
TI  - Screening of concentrations of C-reactive protein and various plasma protease
      inhibitors preoperatively for the prediction of postoperative complications.
AB  - OBJECTIVE: To find out whether concentrations of albumin (reflecting nutritional
      state), C-reactive protein (reflecting an acute phase reaction) or plasma
      protease inhibitors (reflecting ongoing proteolysis) are good predictors of
      postoperative complications, and whether other biochemical tests may improve
      diagnostic accuracy. DESIGN: Retrospective study. SETTING: University hospital,
      Sweden. SUBJECTS: 260 patients undergoing elective surgery for malignant (n =
      149) or benign (n = 111) disease. MAIN OUTCOME MEASURES: Preoperative biochemical
      plasma measurements and postoperative complications. RESULTS: 192 patients
      recovered uneventfully and 35 had minor and 33 major postoperative complications.
      An increased plasma C-reactive protein concentration preoperatively, as well as a
      reduced albumin concentration, predicted the risk of developing major
      postoperative complications. Measurement of plasma protease inhibitors (C1
      esterase inhibitor, alpha-2-macroglobulin and antithrombin III), specific
      biochemical studies of microheterogeneity, or comparison of quantitative and
      functional concentrations of the inhibitors gave no additional information.
      CONCLUSION: One measurement of the C-reactive protein and albumin concentrations
      preoperatively will identify patients at risk of developing severe postoperative
      complications.

PMID- 9537716
TI  - Complement activation and release of interleukin-6 and tumour necrosis factor
      alpha in drained and systemic blood after major orthopaedic surgery.
AB  - OBJECTIVE: To measure the concentration of complement activation products C3bc
      and terminal complement complex (TCC) and the cytokines interleukin 6 (IL-6) and
      tumour necrosis factor alpha (TNF-alpha) in systemic and drained wound blood for
      the first six hours after a major orthopaedic operation. DESIGN: Prospective
      study. SETTING: University hospital, Norway. PATIENTS: 8 patients operated on for
      thoracic scoliosis. MAIN OUTCOME MEASURE: Concentrations of complement activation
      products, IL-6 and TNF-alpha in arterial (systemic) and drained (local) blood
      were measured at wound closure and 1, 2, 4, and 6 hours postoperatively. RESULTS:
      C3bc and TCC were 10 times higher, and IL-6 showed extreme values, in drained
      compared with arterial blood. The concentration of TNF-alpha did not increase
      significantly, either in drained or in arterial blood. The white cell count (WCC)
      increased threefold in both drained and arterial blood compared with arterial
      control values before operation. CONCLUSION: Complement activation and IL-6
      release after surgical trauma differ significantly in local and systemic blood
      samples. Conclusions based only on systemic findings may be limited.

PMID- 9537717
TI  - Treatment of severe injuries caused by attempted suicide: pattern of injury and
      influence of the psychiatric disorder on the postoperative course.
AB  - OBJECTIVE: To assess the influence of psychiatric disorders on the treatment and
      postoperative course of patients severely injured as a result of attempted
      suicide. DESIGN: Retrospective case study. SETTING: University hospital, Germany.
      SUBJECTS: 36 patients who had multiple injuries after attempting suicide during
      the five year period 1991-95. INTERVENTIONS: Operative and psychiatric treatment.
      MAIN OUTCOME MEASURE: Functional results assessed with the Trauma Outcome Profile
      (TOP) score, psychiatric state, and risk of further suicide attempts. RESULTS: 30
      of the 36 patients attempted suicide by jumping from a height, and the most
      common injuries were fractures of the spine (n = 33) and lower limbs (n = 43).
      All patients had a psychiatric disorder, and 18 had previously attempted suicide
      at least once though had inflicted only minor injuries. 29 of the 36 were
      receiving psychiatric care at the time of the suicide attempt. Five patients
      died. 27 of the 31 survivors were available for follow up and 26 of them had good
      or excellent functional results. 30 of the 31 underwent psychiatric assessment
      (one refused) and none was judged to be at risk of a further attempt.
      CONCLUSIONS: The functional results were better than we expected. The
      psychological effect of severe injuries and a long hospital stay seems to reduce
      the risk of a further attempt, so all treatment (both surgical and psychiatric)
      is worthwhile.

PMID- 9537718
TI  - Pathophysiological response of cytokines and vasoactive agents in patients
      undergoing total gastrectomy.
AB  - OBJECTIVE: To investigate the involvement of vasoactive agents, endothelin (ET)
      1, and atrial natriuretic peptide (ANP), and the responses of cytokines in
      patients undergoing total gastrectomy. DESIGN: Prospective study. SETTING:
      University hospital, Japan. SUBJECTS: 20 patients with advanced gastric cancer
      who had undergone total gastrectomy with lymph node dissection. INTERVENTIONS:
      Serum or plasma samples collected on the day before the operation, at the time of
      skin closure, and on postoperative days 1, 3, 5, and 7. MAIN OUTCOME MEASURES:
      Concentrations of acute phase reactants, cytokines (interleukin (IL)-1, tumour
      necrosis factor (TNF) and interleukin (IL)-6), and vasoactive agents (ET-1 and
      ANP). RESULTS: There were significant increases in concentrations of IL-6 and
      acute phase reactants postoperatively. ET-1 and ANP concentrations did not change
      significantly. CONCLUSION: There was no correlation between concentrations of the
      vasoactive agents ET-1 and ANP, and those of acute phase reactants or cytokines
      in serum or plasma in patients undergoing total gastrectomy.

PMID- 9537719
TI  - Quality of life after surgical treatment of gastric carcinoma.
AB  - OBJECTIVE: To see if there was a correlation between self-assessment and external
      evaluation of quality of life (QL) after resection of gastric carcinoma, a
      correlation between overall QL and different components, and the impact of social
      and medical factors on QL. DESIGN: Prospective study. SETTING: University
      hospital, Germany. SUBJECTS: 71 patients assessed once 12 months after R0
      resection of gastric carcinoma and 35 patients assessed regularly, starting
      postoperatively. INTERVENTIONS: QL was assessed by the patients using the
      European Organisation for Research and Treatment of Cancer (EORTC) core QL
      questionnaire (QLQ-C36) and by a psychologist using the Spitzer Index. MAIN
      OUTCOME MEASURES: Correlations between self-assessment and external assessment,
      between overall scores and single items of QL, and between social and medical
      factors and QL, as well as changes in QL-scores during postoperative follow-up.
      RESULTS: Self-assessment and external evaluation of global QL showed a
      significant but not particularly close correlation (r = 0.40) and QL was
      evaluated as better by the external observer using the Spitzer Index. All
      physical, emotional, and social components of the QLQ-C36 correlated
      significantly with patients overall evaluation of QL. Postoperative QL was
      affected mainly by somatic complaints and physical limitations. Of several
      factors analysed, tumour recurrence was the decisive factor in deciding patients'
      QL. Compared with the preoperative assessment, QL had deteriorated on discharge
      from hospital but was restored during the following six months in patients who
      remained disease-free. CONCLUSION: Compared with the Spitzer Index the QLQ-C36
      differentiates the QL of patients with gastric cancer better and disease-specific
      complaints are included.

PMID- 9537720
TI  - Is pyloric function preserved in pylorus-preserving pancreaticoduodenectomy?
AB  - OBJECTIVE: To assess the function of the pylorus after pylorus-preserving
      pancreaticoduodenectomy (PPPD) done for periampullary or pancreatic cancer.
      DESIGN: Prospective, observational controlled clinical study. SETTING: Teaching
      hospital, Italy. SUBJECTS: 17 patients who had undergone PPPD, and 15 healthy
      control subjects. INVESTIGATIONS: Endoscopy to check for gastritis and marginal
      ulcers and 24 h-pH monitoring and 99mTc HIDA scintigraphy to detect jejunogastric
      reflux. Scintigraphy was also used to evaluate gastric and jejunal transit after
      a solid meal labelled with 99mTc colloid sulphur. MAIN OUTCOME MEASURES: Signs of
      delayed gastric emptying, jejunogastric reflux and gastric outlet obstruction in
      the short and long term. RESULTS: In the early postoperative period only 1
      patient had delayed gastric emptying. In the long term, two patients had symptoms
      of dyspepsia and 8/11 showed alkaline reflux with persistent gastric pH more than
      4 for more than 12 hours; 3 had histological signs of gastritis. There was no
      difference in gastric emptying compared with controls, but three patients had
      prolonged emptying time (T1/2 more than 85 minutes). Endoscopy findings
      correlated with pH monitoring results. CONCLUSIONS: After PPPD, most patients
      have abnormal pyloric function, but it is clinically evident in only a small
      proportion.

PMID- 9537721
TI  - In vivo measurement of human body composition by dual-energy X-ray absorptiometry
      (DXA).
AB  - OBJECTIVE: To evaluate measurements of human body composition using dual energy X
      ray absorptiometry and to assess its precision and variations within and between
      observers as well as the influence of food and fluid intake. DESIGN: Experimental
      study. SETTING: District hospital, Denmark. SUBJECTS: 17 volunteers, 12 male and
      5 female. INTERVENTIONS: Repeated scans under standard conditions. MAIN OUTCOME
      MEASURES: Precision, variations within and between observers, and influence of
      the degree of hydration. RESULTS: The repeatability coefficients and the
      coefficients of variation (CV) were obtained for the four body compartments:
      tissue mass 416 g (CV 0.2%); fat mass 1117 g (CV 2.6%); lean tissue mass 1425 g
      (CV 0.9%), and total bone mineral content, (BMC) 109 g (CV 1.2%). There was no
      significant intraobserver variation. There was little interobserver variation in
      assessing tissue mass and BMC, but there were significant differences when
      judging fat and lean tissue mass. Drinking resulted in significantly increased
      values for tissue and lean tissue mass, which corresponded to the intake.
      CONCLUSION: DXA is precise and reproducible with little variation within and
      between observers. It might be useful in clinical studies.

PMID- 9537723
TI  - Graft reconstruction using an intraluminal balloon catheter in ruptured abdominal
      aortic aneurysms.

PMID- 9537722
TI  - Efficacy of preconditioning with N-acetylcysteine against reperfusion injury
      after prolonged cold ischaemia in rats liver in which glutathione had been
      reduced by buthionine sulphoximine.
AB  - OBJECTIVE: To investigate the ability of N-acetylcysteine (NAC) to prevent cold
      ischaemic-reperfusion injury and improve hepatic integrity in a glutathione
      depleted condition. DESIGN: Open laboratory study. SETTING: University hospitals,
      Japan and France. MATERIALS: 40 male Wistar rats. INTERVENTIONS: To produce a
      glutathione-depleted liver, buthionine sulphoximine (BSO) was injected
      intraperitoneally 2 hours before either NAC or 5% dextrose was infused 15 minutes
      before the liver was harvested. We used an isolated perfused rat liver model that
      had undergone prolonged hypothermic ischaemia, cold-storage for 48 hours and
      reperfusion for 120 minutes. MAIN OUTCOME MEASURES: Concentrations of hepatic
      enzymes released into samples of perfusate, concentration of adenosine
      triphosphate in liver tissue, concentrations of reduced and oxidized glutathione
      in perfusate, and bile production. RESULTS: The concentrations of the
      hepatocellular enzymes and oxidised glutathione in the perfusate samples were
      significantly reduced in the NAC group compared with the 5% dextrose group. Bile
      production improved significantly in the NAC group compared with the 5% dextrose
      group. The concentration of reduced glutathione in liver tissue was not increased
      by NAC. CONCLUSION: In a glutathione-depleted liver NAC prevented hepatic injury
      and improved liver integrity after a cold ischaemic-reperfusion injury, by acting
      not as a substrate for glutathione synthesis but as a direct free radical
      scavenger.

PMID- 9537724
TI  - Subcutaneous splenosis: report of a case diagnosed 36 years after splenectomy.

PMID- 9537725
TI  - Acute strangulation of the appendix within a laparoscopic port-site hernia.

PMID- 9537726
TI  - An insidious case of streptococcal soft tissue infection.

PMID- 9537727
TI  - Delmopinol hydrochloride- and chlorhexidine digluconate-induced precipitation of
      salivary proteins of different molecular weights.
AB  - Gel electrophoresis was used to analyze precipitates formed of delmopinol
      hydrochloride or chlorhexidine digluconate mixed with unstimulated whole saliva
      samples from five test subjects. Final concentrations of delmopinol (6.4 mM) or
      chlorhexidine (6.4 mM, 2.2 mM) mixed with whole saliva were incubated for 10 min
      at 37 degrees C. The precipitates were pelleted by centrifugation and resuspended
      to a similar protein density. The protein patterns in the pellets were analyzed
      by sodium dodecyl sulfate polyacrylamide gel electrophoresis, using 12.3% gels.
      The amount of pellet protein was determined by densitometry in four molecular
      weight ranges (10-21.5, 21.5-26, 26-45, and 45-300). The results indicated that
      high molecular weight (45-300) proteins dominated in the precipitate and that 2.2
      mM chlorlhexidine precipitated more salivary protein than 6.4 mM. At equimolar
      concentration (6.4 mM) delmopinol precipitated more high molecular weight
      salivary proteins than chlorhexidine.

PMID- 9537728
TI  - Shear bond strength of a resin cement to densely sintered high-purity alumina
      with various surface conditions.
AB  - Procera Sandvik AB is now manufacturing a densely sintered high-purity alumina
      core for an all-ceramic crown designed for anterior and posterior restorations.
      Whereas the material holds promise on the basis of in vitro strength tests, the
      ability to alter the surface and use conventional bonded resin cements has not
      been reported previously in the literature. Samples of the core were treated by
      means of one of four methods routinely used for all ceramic restorations, and
      then a commercially available resin cement was bonded to the surface. A shear
      bond test of the adhesion showed that the highest shear bond strengths of 11.99
      +/- 3.12 MPa were obtained with air abrasion at 80 psi and 50-microm alumina
      particles.

PMID- 9537729
TI  - Aspects of teeth from archaelogic sites in Sweden and Denmark.
AB  - The purpose of this study was to examine ground sections of primary second molars
      and permanent first molars from the same jaws. Teeth from 11 individuals were
      collected from archaeologic sites in Sweden and Denmark. Longitudinal
      buccolingual sections were examined in a polarization light microscope and in a
      Philips scanning electron microscope (SEM). The seven teeth from Sweden appeared
      to have been subjected to environmental influences at their burial site, which
      had affected both the dentin and the enamel. The teeth from the Danish sites had
      a normal color, and no disintegration of the dentin was seen. The general
      morphologic appearance was normal in all primary and permanent teeth. The
      position of the neonatal line indicated a normal full-term gestational age. The
      observed accentuated incremental lines in both the primary and permanent enamel
      suggested periods of dietary changes, possibly related to periods of illness. SEM
      images of the surface area of the Swedish teeth showed an extremely porous enamel
      surface with severe changes in the prism structure as an effect of acid
      penetration. The Danish teeth did not show any marked changes in the enamel.

PMID- 9537730
TI  - Timing of first fillings in the primary dentition and permanent first molars of
      asthmatic children.
AB  - The aim of this study was to analyze the timing of first fillings posteruptively
      in a cohort comprising 51 asthmatic children receiving inhaled corticosteroids
      and living in three communities in Ostrobothnia, Finland. They had all been born
      in the 1980s and had had asthma check-ups in the local asthma policlinic. A group
      of 102 healthy age- and sex-matched children served as controls. A longitudinal
      survival analysis of the timing of the first filling in the primary teeth and
      first permanent molars was conducted retrospectively using data from the annual
      dental health records. The timing of the first fillings in permanent first molars
      showed no statistically significant differences between asthmatic and healthy
      children, but the filling increments in the primary molars were consistently
      higher in the asthmatic group; the difference for the upper first primary molars
      was, for instance, statistically significant (risk ratio = 2.565; 95% confidence
      interval = 1.333-4.935). More extractions because of caries were also performed
      on primary molars in the asthmatic children. The findings support the hypothesis
      that factors related to the asthmatic condition might increase the risk of
      caries. A longer surveillance time would be needed to evaluate the effect of
      asthma on the permanent dentition.

PMID- 9537731
TI  - The effect of locally applied gauze drain impregnated with chlortetracycline
      ointment in mandibular third-molar surgery.
AB  - A prospective randomized crossover, within-patient, controlled study was
      performed in 26 healthy patients to test the effect of the prophylactic local use
      of gauze drain impregnated with chlortetracycline (Aureomycin 3%, Lederle)
      ointment on postoperative alveolitis formation after surgical removal of 52
      bilaterally impacted mandibular third molars. The teeth were removed on two
      separate occasions; on one side drain was inserted in the socket, and on the
      other side no drain treatment was used for control. The influence on
      postoperative pain, swelling, and mouth opening ability was investigated. The
      results indicated a statistically significant reduction (P = 0.02) in the
      incidence of postoperative inflammatory complications, defined as postoperative
      alveolitis, from 35% in the no-drain group to 4% in the drain group. No
      statistically significant difference was found between the two treatment methods
      with regard to pain and mouth opening reduction. There was a significant
      difference between the drain and no-drain treatment with regard to swelling on
      the 1st postoperative day in favor of the no-drain method. It is concluded that
      insertion of a chlortetracycline-impregnated drain may be an effective method for
      reducing postoperative alveolitis formation but has no beneficial effect on pain,
      swelling, and mouth opening reduction after impacted mandibular third-molar
      surgery.

PMID- 9537732
TI  - Changes in control systems assessed by publicly employed dentists in comparison
      with other professionals.
AB  - In the public service sector in Sweden, including dentistry, changes in
      management control systems have occurred. The extent and content of such self
      assessed changes are described and analyzed for dentists in relation to other
      academicians. A questionnaire was answered by 306 dentists in the Public Dental
      Health Service and 3600 other academicians in Sweden. The response rate was 67%
      77%. Three areas of change were found in factor analysis: management by
      objectives, by dialogue, and by hierarchy. In logistic regression models,
      dentists reported fivefold increases in management by objectives as compared with
      other academicians. Reported increases in management by dialogue were less for
      dentists. Having a female supervisor was related to increase of management by
      hierarchy. It is concluded that clear changes in management style have occurred
      and that dentists are notable for increase of management by objectives.

PMID- 9537733
TI  - Bulimia and tooth erosion.
AB  - Eating disorders are often associated with regurgitation of gastric contents into
      the mouth and dental erosion. In this study the dental status was evaluated in
      bulimic patients. Thirty-five bulimics, diagnosed in the Outpatient Departments
      of Psychiatry and Adolescent Psychiatry of the University Central Hospital in
      Helsinki, and 105 controls matched for age, sex, and educational level were
      examined clinically, and the factors associated with dental erosion and caries
      were evaluated in an interview. Severe dental erosion and dental caries were
      significantly commoner among bulimics than controls. Bulimics commonly had a low
      salivary flow rate, but other apparent risk factors of dental erosion did not
      differ from those of controls. A feeling of dry mouth was commoner among bulimics
      than controls, and bulimics had an increased tooth sensitivity to cold and touch.
      More should be done to protect teeth from dental erosion among bulimics, because
      loss of tooth tissue remains even if the eating disorder disappears.

PMID- 9537734
TI  - Utilization of dental services in relation to socioeconomic and health factors in
      the middle-aged and elderly Swedish population.
AB  - The aims of this study were to describe the change in reported time since the
      latest visit to a dentist between the years 1980/81 and 1988/89 and the reported
      use of dental services in relation to age, dental state, and socioeconomic and
      health characteristics in a sample of the Swedish population in 1988/89. The
      studies are based on interviews by Statistics Sweden about the living conditions.
      In the investigations in 1980/81, 14,964 inhabitants between 16 and 84 years of
      age participated, and in 1988/89, 13,309 inhabitants. In all age groups there was
      a significantly higher frequency of reported visits to a dentist last year in
      1988/89 than in 1980/81. In the age group 50-64 years old this figure increased
      from 54% to 75%, and in the age group 65-84 years old it increased from 26% to
      39%. In the investigation in 1988/89 about 75% of the dentulous women in all age
      groups up to 75 years reported visiting a dentist last year. The relative risk
      for not visiting a dentist last year, adjusted for age, gender, and dental state,
      was higher in dentulous subjects with low income and education, not married, not
      native-born, living in rural areas, smoking, and low social and physical
      activity. The results of the logistic regression analysis showed that, among the
      elderly, functional ability and general health factors have lower significance
      for time since last visit to a dentist than socioeconomic, social support, and
      life-style factors.

PMID- 9537735
TI  - A method for communication analysis in prosthodontics.
AB  - Particularly in prosthodontics, in which the issues of esthetic preferences and
      possibilities are abundant, improved knowledge about dentist patient
      communication during clinical encounters is important. Because previous studies
      on communication used different methods and patient materials, the results are
      difficult to evaluate. There is, therefore, a need for methodologic development.
      One method that makes it possible to quantitatively describe different
      interaction behaviors during clinical encounters is the Roter Method of
      Interaction Process Analysis (RIAS). Since the method was developed in the USA
      for use in the medical context, a translation of the method into Swedish and a
      modification of the categories for use in prosthodontics were necessary. The
      revised manual was used to code 10 audio recordings of dentist patient encounters
      at a specialist clinic for prosthodontics. No major alterations of the RIAS
      manual were made during the translation and modification. The study shows that it
      is possible to distinguish patterns of communication in audio-recorded dentist
      patient encounters. The method also made the identification of different
      interaction profiles possible. These profiles distinguished well among the audio
      recorded encounters. The coding procedures were tested for intra-rater
      reliability and found to be 97% for utterance classification and lambda = 0.76
      for categorization definition. It was concluded that the revised RIAS method is
      applicable in communication studies in prosthodontics.

PMID- 9537736
TI  - Effect of inferior alveolar nerve axotomy on periodontal and pulpal blood flow
      subsequent to experimental tooth movement in rats.
AB  - The aims of this study were to evaluate the effect of inferior alveolar nerve
      (IAN) axotomy on periodontal (PDL) and pulpal blood flow incident to experimental
      tooth movement and to investigate whether nerve fiber regeneration coincides with
      blood flow changes. The first right mandibular molar was moved mesially for 3, 7,
      and 14 days after ipsilateral IAN axotomy in 29 rats. Four rats served as
      unoperated controls. At the end of each experimental period fluorescent
      microspheres (FM) were injected into the left ventricle and thereafter counted in
      serial sections in the PDL and pulp of the right and left first mandibular
      molars. The number of FM per tissue volume was taken as a measure of blood flow.
      Re-innervation of nerve fibers was mapped immunohistochemically 7, 14, and 21
      days after IAN axotomy in 9 rats that had no orthodontic appliance. The
      statistical analysis showed no significant differences in the number of FM/mm3
      PDL between the denervated and the contralateral side at 3 and 7 days. At 14 days
      the PDL on the denervated side showed a significant increase in the number of
      FM/mm3, coinciding with the initial periodontal nerve fiber re-innervation. In
      the pulp no significant differences were found between the denervated and the
      contralateral, innervated side in any experimental period. It can be concluded
      that IAN axotomy postpones an increase in periodontal blood flow until a sensory
      tissue re-innervation is established, thus indicating that neurogenic mechanisms
      play an important role in the development of the inflammatory reaction induced by
      experimental tooth movement.

PMID- 9537737
TI  - Improving health and reducing costs through information technology.

PMID- 9537738
TI  - "Biofilms on Oral Surfaces: Implications for Health and Disease." 14th
      International Conference on Oral Biology. Monterey, California, March 18-20,
      1996.

PMID- 9537739
TI  - Death and the general practitioner.

PMID- 9537740
TI  - Porphyrin binding to quadrupled T4G4.
AB  - We have recently reported the cation-induced self-assembly of DNA oligomers of
      the general sequence C4T4G4T1-4G4 into high-molecular weight multistranded
      structures [Marotta, S.P., Tamburri, P.A., and Sheardy, R.D. (1996) Biochemistry
      35, 10484-10492]. The architecture of the proposed structure consists of a series
      of four leafed G4 tetrads tethered together via one or two T1-4 strands and thus
      resembles a long four-sided hollow tube with periodic "pockets". These pockets
      possess electrostatic, hydrogen bonding, and hydrophobic contact points and
      should be ideal candidates for the binding of small molecules. To assess the
      potential of using porphyrins as probes for these structures, we have
      investigated the interaction of tetrakis(4-N-methylpyridyl)porphine (H2TMPyP)
      with the simple quadruplex formed by T4G4 and with the duplex formed by
      CGCGATATCGCG. Visible absorption, circular dichroism, and fluorescent energy
      transfer studies indicate that H2TMPyP binds to both the duplex and quadruplex
      via intercalation at low [porphyrin]/[DNA molecule] ratios, i.e., in the presence
      of excess potential DNA binding sites. Analyses of Scatchard plots show that
      H2TMpyP binds with high affinity to both DNA secondary structures but binds to
      the quadruplex with an affinity 2 times greater than that of the duplex.

PMID- 9537742
TI  - [Diseases of bivalve mollusks: risk and prevention].
AB  - The farming of shellfish, based on fishing and rearing in a natural environment,
      has developed considerably in recent years, particularly as a result of
      production of spat and juveniles in hatcheries and nurseries. The growing demand
      for trade in products, facilitated by modern means of transport, has increased
      the risks of disease spread. Using examples, the author analyses the risks
      incurred by shellfish farming methods and the risks linked to the present state
      of knowledge. Recommendations are made on prevention and the need for
      regulations, and difficulties encountered in this area are discussed. Finally,
      proposals are made to overcome the existing antagonism between marked demands and
      the need to protect shellfish farming.

PMID- 9537741
TI  - [Risk of transmission of foot and mouth disease by milk and its products:
      perspectives in South America].
AB  - The authors highlight the importance of trade in dairy products in South America
      and throughout the world, and discuss the problem of restrictions engendered by
      foot and mouth disease (FMD) on exports to countries free from the disease. The
      epidemiological features of the disease and properties of the causal agent are
      described in relation to the dairy industry, with special reference to survival
      of the virus. Discussion then focuses on the risk of foot and mouth disease in
      relation to the effects the disease has on animal production before and after
      milking and the industrial processing of dairy products. Finally, the authors
      review progress achieved in FMD control and eradication programmes in Latin
      America, particularly in the southern sector where countries such as Chile and
      Uruguay are free from the disease, while in other countries (such as Argentina,
      Paraguay and parts of southern Brazil) no case has been reported for more than
      two years. It is concluded that dairy products can be exported from the region
      without creating a risk to animal health, provided that there has been proper
      risk analysis, according to the clearly defined regionalization criteria.

PMID- 9537743
TI  - [Risk of disseminating apiary diseases by international movements of bees and
      their products].
AB  - The evaluation of the risks of spreading bee diseases is based on information
      obtained from a wide variety of sources: reports of the world distribution of
      pathogenic agents; trade flow in bees and bee products; and observations and
      experimental data on the diseases. At present, this information is severely
      lacking and only enables a brief outline of trends to be made. Current data are
      inadequate to prevent the spread of diseases from one country to another. To
      improve this situation, it is important that exporting countries establish
      epidemiological and health surveillance practices based on harmonised procedures
      and diagnostic tests. In addition, the products of apiculture should be given a
      permanent, specific nomenclature, drawn up by the World Trade Organisation.

PMID- 9537744
TI  - [Risk for the transmission of Newcastle disease by contaminated poultry
      products].
AB  - Poultry products contaminated with pathogenic strains of Newcastle disease virus
      are a source of virus transmission to susceptible poultry flocks. The probability
      of contamination varies according to the type of product. Research conducted by
      various laboratories in Europe has shown that pathogenic virus can be isolated
      from the carcasses of chickens, whether vaccinated or not, during a brief period
      after experimental infection. Eggs laid by hens infected with Newcastle disease
      virus present a very low risk. Furthermore, feathers, bones, blood and offal
      present potential risks if they are incorporated in poultry feed. Finally,
      poultry droppings used as a fertiliser can present a major risk of infection in
      certain circumstances.

PMID- 9537745
TI  - [The risk of transmission of salmonellae in poultry farming: detection and
      prevention in Europe].
AB  - While salmonellas can cause disease problems among poultry, they remain
      essentially a concern for public health, as a cause of outbreaks of food
      poisoning. The principal site of multiplication of these bacteria is the
      digestive tract, particularly the caecum, which may result in widespread
      contamination of the environment. The pathogenicity of salmonellas depends on the
      invasive properties and the ability of the bacteria to survive and multiply
      within cells, particularly macrophages. These properties are the source of
      vertical transmission which, in the case of survival of the embryo, can result in
      contamination of a flock or, in the case of embryonic mortality, can result in an
      explosion of contaminated eggs. Salmonella infection can be diagnosed by
      isolating the bacteria and/or serological testing of the flock. European Union
      Directive 92/117/EC, modified by Directive 97/22/EC, stipulates either the
      destruction of infected flocks of breeding birds, or decontamination of the flock
      in an effective way, before normal trade in products can be resumed. Noteworthy
      examples of effective measures suitable for prophylaxis of Salmonella infection
      in poultry flocks include the slaughter of infected breeding stock, the creation
      of sanitary barriers at building entrances, heat treatment of feed, the use of
      competitive exclusion, selection of breeds genetically resistant to Salmonella,
      and occasional vaccination and antibiotic treatment. However, the most effective
      means of reducing food poisoning remains adequate cooking of food and maintenance
      of the cold chain.

PMID- 9537746
TI  - [Model for evaluating the risk of introducing rabbit viral hemorrhagic disease
      based on experience in Mexico].
AB  - Viral haemorrhagic disease (VHD) of rabbits was introduced into Mexico from the
      United States of America in November 1988, following the importation of infected
      carcasses from China. In February 1989, the National System for Animal Health
      Emergencies was created, and an eradication programme was implemented at that
      time. The VHD virus was eradicated in 1992, by means of disease control
      procedures which included active epidemiological surveillance, publicity
      campaigns, slaughter, cleaning and disinfection of affected premises, the use of
      sentinel animals, serological monitoring and repopulation. The eradication
      programme involved the serological sampling of 39,727 rabbits (revealing an
      incidence of 1.4%) and the slaughter of 121,275 affected rabbits and rabbits at
      risk of exposure to infection. The final outbreak of the disease was recorded in
      April 1991. The country maintained strict epidemiological surveillance through
      serological testing, certification of premises free from the disease, and control
      of movement of animals and animal products. Mexico was declared free from the
      disease on 20 January 1993, becoming the first country to have eradicated VHD.
      The authors propose a model to evaluate the risk of introducing VHD through the
      importation of animals and animal products. A guide is provided to evaluate each
      branch of the relevant scenario tree and the principal criteria which indicate
      the event at each parameter.

PMID- 9537747
TI  - Advances in DNA diagnostics.
AB  - The key advances in DNA diagnostics during the past year are techniques which
      will lead to advanced throughput without sacrificing sensitivity: miniaturization
      of samples to reduce material cost and preparation time, and parallelization
      through use of measurement arrays. The most promising gains have come in the
      areas of DNA arrays and mass spectrometry, where differential sequencing
      measurements are now possible.

PMID- 9537748
TI  - Web alert. Analytical biotechnology.

PMID- 9537749
TI  - Serological reactivity of humans to a Vibrio cholerae common antigen.
AB  - Over the course of seven pandemics, Vibrio cholerae serotypes have varied. In
      1992 the appearance of a new serotype, O139 Bengal, began the eighth cholera
      pandemic. Several new O139 antigens have been identified, yet a common V.
      cholerae antigen has not been described. In this study, a monoclonal antibody
      specific against an 18.7-kDa outer membrane antigen reacted in dotblot analysis
      with 292 epidemiologically diverse V. cholerae isolates including O1, non-O1, and
      O139 serotypes. Serum collected from volunteers experimentally challenged with V.
      cholerae O139, and rabbit antisera to V. cholerae O1, were reactive with the 18.7
      kDa antigen by Western immunoblot. This is the first report that the 18.7-kDa
      antigen is present in V. cholerae O139.

PMID- 9537750
TI  - Influence of blood transfusion on bactericidal activity of human leukocytes and
      sera against Yersinia enterocolitica and Salmonella typhimurium.
AB  - Patients undergoing joint surgery and blood transfusion were studied. Serum and
      leukocyte bactericidal tests in vitro against Salmonella typhimurium and Yersinia
      enterocolitica were carried out preoperatively as well as on the 1st, 3rd and 7th
      days after the operation. The serum complement (C3 and C4) concentrations were
      determined at the same intervals. It was found that after blood transfusion the
      bactericidic activity of sera and the serum C3 complement concentrations were
      increased. In contrast the killing ability of leukocytes was suppressed.

PMID- 9537751
TI  - Quantitative analysis and isolation of Escherichia coli O157:H7 in a food matrix
      using flow cytometry and cell sorting.
AB  - Flow cytometry is a potentially valuable analytical method in microbiology
      providing the ability to analyze rapidly large numbers of individual
      microorganisms by several parameters. With a flow cytometer with enhanced light
      scatter sensitivity and a conventionally configured sorting cytometer, a series
      of comparative studies to determine the ability of the two flow systems and the
      antibody-direct epifluorescent filter technique (Ab-DEFT) to detect and enumerate
      Escherichia coli O157:H7 were made. Initial experiments used culture-derived
      mixtures of non-pathogenic E. coli and serial dilutions of E. coli O157:H7.
      Subsequent studies involved analysis of enrichment cultures from ground beef
      inoculated with E. coli O157:H7. Comparison of flow cytometry with microscopy and
      plate counts produced similar results at higher concentrations in both culture
      mixtures and beef enrichments. At the lowest concentrations Ab-DEFT was more
      sensitive, however, the time required for analysis was much less with flow
      cytometry. With a cytometer with enhanced light scatter sensitivity designed for
      bacterial analysis, O157:H7 could be distinguished from E. coli strain HB101 on
      the basis of light scatter. This instrument also provided direct count data for
      selected populations. In experiments using cell sorting to isolate target
      organisms, the purity of fluorescent-labeled E. coli O157:H7 sorted from beef
      enrichment cultures and plated was not affected by the level of background
      organisms, as is often the case in conventional plating procedures.

PMID- 9537752
TI  - Mycoplasma salivarium induces interleukin-6 and interleukin-8 in human gingival
      fibroblasts.
AB  - Analysis by an enzyme-linked immunosorbent assay for cytokines indicated that
      whole cells, intracellular materials and cell membranes of Mycoplasma salivarium
      induced interleukin-6 and interleukin-8 in a human gingival fibroblast cell line,
      Gin-1 cells. This was confirmed by reverse transcription-polymerase chain
      reaction analysis of mRNAs of these cytokines. Studies with inhibitors of second
      messenger pathway indicated that a protein kinase C-dependent pathway was
      involved in the expression of the activity of the cell membranes. In addition,
      whole cells of other mycoplasmas (M. hominis, M. arthritidis, M. arginini, M.
      fermentans, M. penetrans, M. pirum and M. pneumoniae) tested for comparative
      purposes were also shown to possess the activity. Thus, this study demonstrated
      that mycoplasmas possess the activity to induce interleukin-6 and interleukin-8
      in human fibroblasts.

PMID- 9537753
TI  - Culture supernatant of Shiga toxin-producing Escherichia coli strains provoke
      fluid accumulation in rabbit ileal loops.
AB  - Production of Shiga toxin (Stx) in Escherichia coli strains belonging to
      serogroups O26, O111, and O157 was evaluated in the rabbit ileal loop assay and
      results were compared to those using tissue culture assays and DNA hybridization
      with specific probes for Stx1 and Stx2. All 14 Shiga toxin-producing E. coli
      strains tested provoked fluid accumulation in the rabbit intestinal loop. Eleven
      strains hybridized with Stx1 probe, one strain with Stx2 and two strains with
      both probes. Filtered culture supernatants of all E. coli strains presented
      cytotoxic effects in both HeLa and Vero cells. In this study, we found a strong
      association between the production of Stx and its effect in an animal model. This
      is the first description of high-level Stx-producing E. coli O111ac isolated in
      Brazil.

PMID- 9537754
TI  - Construction and characterization of type 1 non-fimbriate and non-adhesive
      mutants of Salmonella typhimurium.
AB  - Mutations in the fimH gene of Salmonella typhimurium result in a non-fimbriate,
      non-adhesive phenotype. This phenotype was shown to be due to the lack of both
      fimH and fimF expression since disruption of the fimH gene by insertion of a DNA
      cassette into this determinant results in mutants that are complemented by
      plasmids carrying both fimH and fimF. Deletion mutations within the S.
      typhimurium fimH gene carried on a recombinant plasmid can be used to complement
      the mutant, and these transformants are non-adhesive but fully fimbriate,
      consistent with the role of FimH as being necessary for fimbrial adhesin
      expression. Adherence to erythrocytes, HeLa, and Hep-2 cells is associated with
      expression of the FimH polypeptide, and fimbriate strains that cannot synthesize
      FimH are non-adhesive. Discrete differences in the amino acid sequences of the
      adhesive type 1 and the non-hemagglutinating type 2 FimH polypeptides were
      detected, and are most likely responsible for the differences in hemagglutinating
      activity.

PMID- 9537755
TI  - Stazyme, a mycobacteriolytic preparation from a Staphylococcus strain, is able to
      break the permeability barrier in multiple drug resistant Mycobacterium avium.
AB  - As a strategy to augment the potential of existing drugs against Mycobacterium
      avium we investigated a mycobacteriolytic preparation (stazyme) from the
      Staphylococcus strain Clavelis, which results in significant mycobacterial growth
      inhibition. A total of 10 specific protein bands were characterized in the
      stazyme preparation: three bands within a major 40-60 kDa fraction, five bands
      within the range of 30-90 kDa, and two bands of about 12 and 14 kDa respectively.
      Tested at concentrations of 50 and 200 microg ml(-1) of total protein, stazyme
      was highly bactericidal against M. smegmatis, and bacteriostatic against M.
      tuberculosis and M. avium. Stazyme was able to break the permeability barrier of
      M. avium isolates, significantly enhancing the activity of other antituberculous
      drugs (ethambutol, rifampicin, and amikacin), used at sub-MIC level. Stazyme
      essentially possessed a lytic activity as evidenced by its ability to lyse
      purified M. smegmatis cell walls. This lytic activity was also confirmed on
      intact M. smegmatis and M. avium bacilli by transmission electron microscopy.
      Precise identification of this mycobacteriolytic determinant(s) in stazyme may be
      helpful to define novel drug targets in mycobacteria.

PMID- 9537756
TI  - The use of porphyrins for eradication of Staphylococcus aureus in burn wound
      infections.
AB  - The assessment of deuteroporphyrin-hemin complex as an agent for the treatment of
      burn wounds infected with a multiple-drug resistant strain of Staphylococcus
      aureus was performed. The effect of the porphyrin on the survival of the
      infectious bacteria was first assayed in culture, and later tested as well in a
      burned infected animal model. The addition of deuteroporphyrin and hemin,
      separately or together (as a complex) to a growing culture of S. aureus was
      monitored during 8 hours. It was found that deuteroporphyrin alone was strongly
      bactericidal only after photosensitization. On the other hand, hemin alone was
      moderately bactericidal but light independent. A combination of both
      deuteroporphyrin and hemin was extremely potent even in the dark and did not
      require illumination to eradicate the bacteria. The in vivo experiments by
      application of the above porphyrins in combination to infected burn wounds in
      guinea pigs was an effective way to reduce dramatically the contaminating S.
      aureus. Reduction of more than 99% of the viable bacteria was noted after the
      porphyrin mixture was dropped on the eschar or injected into the eschar, an
      effect that lasted for up to 24 hours. The deuteroporphyrin-hemin complex may be
      suggested as a new bactericidal treatment of S. aureus infected burns since it
      was found to be a potent and promising anti-Staphylococcal agent.

PMID- 9537757
TI  - Human infection by Brucella melitensis: an outbreak attributed to contact with
      infected goats.
AB  - Although several outbreaks of Brucella melitensis infection have been reported
      among laboratory workers or goat cheese consumers, outbreaks related to rural
      labour have been rarely studied. An outbreak of human brucellosis among farm
      workers of Argentina was studied and revealed a close relationship with an
      epidemic of caprine abortions which occurred shortly before on the same farm.
      High rates of B. melitensis infection were found among goats. Active brucellosis
      was diagnosed in 33 subjects (14 with positive blood culture for B. melitensis),
      while other 27 did not show evidence of illness. While 25 of the brucellosis
      active patients were rural workers, only 5 of the healthy subjects were engaged
      in rural labour. Active brucellosis was diagnosed in 91.3% of the subjects in
      continuous contact with goats and in 32% of those having an occasional contact
      with the animals. All the 60 subjects denied consumption of goat cheese or milk.
      As shown here, epidemic human infections by B. melitensis may develop among
      people frequently in contact with infected goat herds or goat manure.

PMID- 9537758
TI  - Evaluation of different subcellular fractions of Vibrio cholerae O139 in
      protection to challenge in experimental cholera.
AB  - Various cellular fractions of Vibrio cholerae O139 were prepared and evaluated in
      the rabbit ileal loop model of experimental cholera for identification of the
      protective antigen(s) relevant for vaccine development. Lipopolysaccharides (LPS)
      and capsular polysaccharides (CPS) of O139 strains and its cell surface, membrane
      and cytosolic fractions were assayed for antibacterial immunity, whereas the
      cholera toxin was examined for antitoxic immunity. The lipopolysaccharides,
      membrane fraction and cholera toxin induced moderate protection, however there
      was a significant synergistic effect when cholera toxin was combined with
      membrane proteins or lipopolysaccharides. The O139 strains strongly resembled O1
      strains in the profile of proteins and immunological cross reactivity, yet there
      was no cross protection. The results warrant further investigation of the
      pathogenesis of O139 strains and identify the critical somatic antigens relevant
      to protection.

PMID- 9537759
TI  - Study of the immunostimulating effect of IM-104 in mice.
AB  - The results of this study show that the product IM-104 has a marked
      immunostimulant effect, when administered intraperitoneally in mice, as seen by
      the increase in the number of haemolytic plaque-forming cells producing
      antibodies against sheep erythrocytes, as compared with saline-treated controls.

PMID- 9537760
TI  - The biosynthesis and processing of vitellogenin in the fat bodies of females and
      males of the cockroach Leucophaea maderae.
AB  - The juvenile hormone analog (JHA) methoprene was used to induce the synthesis of
      the yolk protein precursor vitellogenin (Vg) in adult females and males of the
      cockroach Leucophaea maderae. The female- and male-produced vitellogenin (VgF and
      VgM, respectively) contained polypeptides of 112, 95, 92, and 54 kDa. Also
      present in the secreted vitellogenins was a soffmall quantity of a short-lived
      transitional 155 kDa Vg polypeptide, and a variable amount of an 85 dDa species.
      Quantitatively, the VgF and VgM were significantly different in the Vg112 and
      Vg95 units (VgF > VgM), and in the Vg85 polypeptide (VgF < VgM). In the present
      study, the biosynthesis of Vg precursors in the fat bodies of females and males
      was examined using a short radiopulse with 35S-methionine/cysteine and 32P
      orthophosphate. The glycosylation of the Vg precursors was examined by digestion
      with endoglycosidase H and by the inhibition of N-linked glycosylation with
      tunicamycin. The data showed that in both females and males, the synthesis of the
      vitellogenin precursor occurred in a stepwise fashion: (1) the co-translational
      glycosylation of Vg203; (2) the post-translational phosphorylation of Vg203 to
      form Vg220; (3) the proteolytic processing of Vg220 to form the constituent Vg
      polypeptides. The 203 and 220 kDa Vg precursors of females and males appeared to
      be similarly glycosylated and phosphorylated. The additional processing of Vg112
      to Vg85 was more pronounced in the fat bodies of males than in females, and
      appears to account for the quantitative difference in the distribution of these
      polypeptides in VgF and VgM. Finally, the major oligosaccharides of VgF and VgM
      appear to be those of N-linked mannose residues. The treatment of females and
      males with tunicamycin indicated that the co-translational glycosylation of Vg
      precursors was required for the phosphorylation of the Vg precursor, as well as
      the secretion of Vg from the fat body.

PMID- 9537761
TI  - Isolation and characterization of the cDNA encoding the prophenoloxidase of fall
      webworm, hyphantria cunea.
AB  - Two kinds of cDNA clones encoding prophenoloxidases (ProPO; zymogen of
      phenoloxidase (monophenol, L-dopa: oxygen oxydoreductase, EC 1.14.18.1)) were
      isolated by polymerase chain reaction (PCR) followed by screening of cDNA library
      that was prepared from whole larvae of the fall webworm, Hyphantria cunea
      (Lepidoptera, Arctiidae). The cDNAs encode 681 and 697 amino acids with molecular
      masses of 78.2 and 80.2 kDa, respectively. Deduced amino acid sequence homology
      between the two H. cunea ProPOs are only 49% whereas the homology against other
      insect ProPOs ranged from about 40 to 72%. The phylogenic analysis showed that
      the insect ProPOs are grouped mainly into two families. A putative proteolytic
      cleavage site for enzyme activation was identical to other insect ProPOs. The
      conserved copper binding sites were 84-62% homologous to arthropod ProPOs. Two
      additional highly conserved regions were found in the carboxy terminal.
      Furthermore, like other insect prophenoloxidases, hydrophobic signal peptide
      sequences were absent in the deduced ProPOs from H. cunea. Southern blot analysis
      indicated that the H. cunea ProPO1 is present as a single copy in the genome.
      Northern blot analysis showed that the expression of the ProPO genes were
      concentrated in mid-instar larvae, but were much lower in other developmental
      stages.

PMID- 9537762
TI  - Physical identification of a chromosomal locus encoding biosynthetic genes for
      the lipopeptide calcium-dependent antibiotic (CDA) of Streptomyces coelicolor
      A3(2).
AB  - Putative peptide-synthetase-encoding DNA fragments were isolated from the
      Streptomyces coelicolor A3(2) chromosome using a PCR-based approach and mapped to
      a single approximately 35 kb segment. In integrative transformation experiments,
      DNA fragments from this region disrupted production of the calcium-dependent
      antibiotic (CDA) and had sequences characteristic of non-ribosomal peptide
      synthetases, thus proving that the cda locus had been cloned.

PMID- 9537763
TI  - Effect of cytochalasin A on apical growth, actin cytoskeleton organization and
      enzyme secretion in Aspergillus nidulans.
AB  - The role of actin in apical growth and enzyme secretion in the filamentous fungus
      Aspergillus nidulans was studied by treating the hyphae with cytochalasin A (CA),
      which inhibits actin polymerization. Indirect immunofluorescence microscopy
      revealed actin at the tips of main hyphae and branches, and at the site of
      developing septa. CA inhibited the growth of the fungus and changed the growth
      pattern of hyphal tips from cylindrical tubes to spherical beads. The regions
      with swellings showed no actin fluorescence, and neither was actin seen in
      association with septa. After 4 h exposure, hyphae were able to resume the normal
      tip growth pattern in the presence of CA for a short period of time and new
      cylindrical hyphae, with actin fluorescence at the apex, emerged from the swollen
      tips. Later, the tips of the hyphae swelled again, which led to a beaded
      appearance. We also studied the effect of CA on the secretion of alpha- and beta
      galactosidase. alpha-Galactosidase is secreted into the culture medium, whereas
      beta-galactosidase remains in the mycelium, with part of its activity bound to
      the cell wall. When A. nidulans mycelium was incubated in the presence of CA, a
      reduction in the secretion of alpha-galactosidase into the culture medium and a
      decrease in the alpha- and beta-galactosidase activities bound to the cell wall
      was detected. However, the CA dose used for the hyphae did not modify the
      secretion of the enzymes from protoplasts. Results described here provide
      evidence that a polymerized actin cytoskeleton is required for normal apical
      growth, hyphal tip shape and polarized enzyme secretion in A. nidulans.
      Cytochalasin-induced disruptions of the actin cytoskeleton could result in the
      alterations of apical growth and inhibition of enzyme secretion observed by
      blocking secretory vesicle transport to the apex.

PMID- 9537765
TI  - Oregon voters confirm support for physician-assisted suicide; pharmacists and
      physicians struggle over implementation.

PMID- 9537764
TI  - The role of autolysins during vegetative growth of Bacillus subtilis 168.
AB  - A set of isogenic mutants of Bacillus subtilis 168, insertionally inactivated in
      the genes encoding a number of lytic enzymes and a sigma factor (sigma D, which
      controls the expression of a number of autolysins) was constructed. Phenotypic
      analysis of the mutants determined the individual and combined roles of the
      autolysins in vegetative growth. The major vegetative autolysins of B. subtilis,
      LytC (50 kDa amidase) and LytD (90 kDa glucosaminidase), were shown to have roles
      in cell separation, cell wall turnover, antibiotic-induced lysis and motility.
      LytC was also shown to have a role in general cell lysis induced by sodium azide.
      Renaturing SDS-PAGE of cell-wall-binding protein extracts of the mutant strains
      revealed the presence of a novel autolysin that was previously masked by LytC.
      This 49 kDa enzyme was shown to be sigma D-controlled and was identified as a
      candidate cell separation and cell wall turnover enzyme. A multiple mutant
      strain, lacking LytC, LytD and the 49 kDa enzyme, retained at least ten bands of
      autolytic activity. These may correspond to individual or proteolytically
      processed novel autolysins, the functions of which are unknown. The multiple
      mutant strains facilitate the study of these, and other lytic enzymes, to
      determine their cellular functions.

PMID- 9537767
TI  - Drug-approval pace remains brisk in 1997.

PMID- 9537766
TI  - Improvement needed in nursing home medication review, say government reports.

PMID- 9537768
TI  - Transition to managed care, part 2.

PMID- 9537769
TI  - Toward optimal provision of antithrombotic therapy.

PMID- 9537770
TI  - Serum eosinophil cationic protein in asthma: what does it mean?

PMID- 9537771
TI  - How do lymphocytes get into the asthmatic airways? Lymphocyte traffic into and
      within the lung in asthma.

PMID- 9537772
TI  - Cetirizine and hydrocortisone differentially regulate ICAM-1 expression and
      chemokine release in cultured human keratinocytes.
AB  - BACKGROUND: Cetirizine is a H1 histamine antagonist which possesses anti
      inflammatory properties through inhibition of leucocyte recruitment and
      activation, and reduction of ICAM-1 expression on mucosal epithelial cells. No
      studies have addressed the potential anti-inflammatory activities of cetirizine
      on skin keratinocytes. OBJECTIVES: Cetirizine and hydrocortisone were compared in
      their capacity to counteract human keratinocytes activation by IFNgamma. In
      particular, expression of immuno-modulatory membrane molecules and chemokine
      release have been examined. METHODS: Keratinocyte cultures established from
      normal skin of healthy donors were activated by IFNgamma (100-500 U/mL) in the
      absence or presence of cetirizine (10(-3)-10(3) microM) or hydrocortisone (10(-3)
      10(2) microM), and tested for expression of ICAM-1, HLA-DR, MHC class I and CD40
      as well as for release of RANTES, IL-8, macrophage chemotactic protein-1 (MCP-1)
      and granulocyte macrophage-colony stimulating factor (GM-CSF). RESULTS:
      Cetirizine at high concentrations (10(2)-10(3) microM) markedly inhibited
      IFNgamma-induced expression of membrane ICAM-1, HLA-DR and up-regulation of MHC
      class I, but had no effect on CD40 expression. In contrast, hydrocortisone (10(2)
      microM) enhanced IFNgamma-induced membrane ICAM-1, reduced expression of HLA-DR
      and did not alter expression of MHC class I and CD40. Consistently, high doses of
      cetirizine decreased, whereas hydrocortisone increased, soluble ICAM-1 levels in
      the supernatants of IFNgamma-treated keratinocytes. The inhibiting and
      stimulating effects of cetirizine and hydrocortisone, respectively, on ICAM-1
      expression were confirmed at the mRNA level by Northern blot analysis. Finally,
      cetirizine, but not hydrocortisone, inhibited the release of MCP-1 and RANTES
      from IFNgamma-stimulated keratinocytes. In contrast, hydrocortisone, but not
      cetirizine, reduced GM-CSF and IL-8 release. CONCLUSIONS: The results indicate
      that cetirizine has the capacity to block the IFNgamma-induced activation of
      keratinocytes, and thus can exert important regulatory effects on TH1 cell
      mediated immune responses in the skin. The high doses required for evidencing
      these activities suggest the potential benefits of a topical use of cetirizine.

PMID- 9537773
TI  - Expression of aminopeptidase N and dipeptidyl peptidase IV in the healthy and
      asthmatic bronchus.
AB  - BACKGROUND: Asthma is characterized by reversible airway obstruction, airway
      hyperresponsiveness, and chronic inflammation of the airways. Since peptides are
      able to produce many of the pathophysiological features which are characteristic
      of asthma, peptide-mediated inflammation is thought to play a role in this
      disease. The effects of peptides are modulated by peptidases, which are able to
      degrade peptides, mostly resulting in their inactivation. OBJECTIVES: In this
      study, we investigated the distribution of two peptidases, aminopeptidase N and
      dipeptidyl peptidase IV, in the human bronchus and determined whether their
      expression was altered in allergic asthmatics. METHODS: We first determined the
      distribution of aminopeptidase N and dipeptidyl peptidase IV in the human
      bronchus using immuno- and enzymehistochemistry and compared this with the
      distribution of neutral endopeptidase. Secondly, the expression of aminopeptidase
      N and dipeptidyl peptidase IV was determined in bronchial biopsies of healthy
      subjects (n = 8) and allergic asthmatics (n = 12). RESULTS: Aminopeptidase N was
      localized in connective tissue, blood vessels, gland ducts, perichondrium, nerves
      and leucocytes (mainly mononuclear phagocytes, dendritic cells, and eosinophils).
      Dipeptidyl peptidase IV was localized in serosal glands, blood vessels, and T
      cells. Immunohistochemistry and enzymehistochemistry gave similar results.
      Comparison of the expression of aminopeptidase N and dipeptidyl peptidase IV in
      bronchial biopsies of healthy controls and atopic asthmatics revealed no
      significant differences in the lamina propria. In contrast, in the bronchial
      epithelium of atopic asthmatics an increased number of aminopeptidase N-positive
      cells could be found. Double-staining identified these cells as L25+ dendritic
      cells and eosinophils. CONCLUSIONS: We conclude that expression of aminopeptidase
      N and dipeptidyl peptidase IV is restricted to specific sites within the human
      bronchus. Furthermore, in the bronchial epithelium of allergic asthmatics an
      increased number of aminopeptidase N-expressing dendritic cells and eosinophils
      can be found.

PMID- 9537774
TI  - Anaphylaxis to hair dye: a case report.

PMID- 9537775
TI  - Clinical utility of serum levels of eosinophil cationic protein (ECP) for
      monitoring and predicting clinical course in childhood asthma.
AB  - BACKGROUND: The concentration of ECP in serum has been proposed as a marker of
      airway inflammation in asthma. However, its clinical significance is still to be
      determined. OBJECTIVES: This study was performed to determine whether
      concentration of ECP in serum reflects clinical status in asthma and can serve as
      a predictive parameter. METHODS: Cross-sectional analysis was performed in 28
      children with asthma. A total of 91 blood samples was obtained to determine
      levels of ECP in serum and eosinophil counts. Forced expiratory volume in 1 s was
      also determined at the time of the sampling. Data were analysed on the basis of
      asthma symptoms in the 4 weeks before and the 4 weeks after sampling. RESULTS:
      Serum levels of ECP were significantly lower in patients who had been
      asymptomatic for 3 or 4 weeks before sampling than in patients who had been
      symptomatic or asymptomatic for only 1 or 2 weeks. In the former group, serum
      levels of ECP were higher when patients became symptomatic after sampling than
      when they remained stable, a finding that suggests that serum levels of ECP may
      have a predictive value in certain situations. Although the concentration of ECP
      in serum was not proved to be predictive in the latter symptomatic group, the
      concentration of ECP was significantly lower when measured again 4 weeks later
      when the patients' symptoms had resolved. In contrast, levels of ECP were
      unchanged when patients remained symptomatic, a finding that suggests serum
      levels of ECP may reflect the clinical response to therapy. CONCLUSIONS: Serum
      ECP may be a useful marker for monitoring and predicting the clinical course in
      asthma.

PMID- 9537776
TI  - The frequency and clinical significance of specific IgE to both wasp (Vespula)
      and honey-bee (Apis) venoms in the same patient.
AB  - BACKGROUND: Changeover from Phadebas RAST to Pharmacia AutoCAP increased double
      positivity to both honey-bee and common wasp (vespula) venom in our patients.
      OBJECTIVE: We examined the frequency of IgE double-positivity, its clinical
      relevance and utility in investigating potentially allergic patients. METHODS:
      One hundred and eighty-two patients with hymenoptera allergy were tested using
      RAST (n = 51) and AutoCAP (n = 131) assays over 4 years. Patients had a history
      of reactions to vespulae (22), honey-bee (10) and unidentified hymenoptera
      (vespinae) (7). RESULTS: After changing from RAST to AutoCAP double-positivity
      increased from 10 (5/ 51) to 30% (39/131) (P < 0.01). RAST and CAP assays gave
      similar median class results (vespula = 3, honey-bee = 2). Thirty-six CAP
      patients had systemic reactions of Mueller grade II and above. In vespula
      allergic double-positive subjects, high CAP classes (> or = class 3) to honey-bee
      were common (30%). In 25% the CAP classes were equal. In honey-bee-allergic
      subjects, all vespula venom CAP IgE was low titre (class 1 or 2) and 20% were
      equal for both venoms. In 43% of vespinae-allergic patients the CAP class was
      equal to both (class 2 and 3). In contrast, intradermal skin test double
      positivity was uncommon. Double-negative skin test results were common in the CAP
      double-positive population (22% of honey-bee-allergic, 13% of vespula-allergic
      and 43% of vespinae-allergic patients). Vespula allergic patients have higher bee
      venom IgE than vice versa. Twenty-seven per cent of CAP double-positive patients
      (representing 8% of all venom allergic patients tested over this period) had
      equal class IgE to both venoms which was not helpful in diagnosis. Combination of
      skin testing and CAP is unhelpful in only 5/37 (14%) of patients with double
      positive serology. CONCLUSION: If used in isolation CAP may be misleading,
      especially if only one venom is tested. Identification of the causative venom
      must utilize both clinical history and skin testing in these double-positive
      patients, and challenge testing if indicated.

PMID- 9537777
TI  - CD4+ cells proliferate after peanut-extract-specific and CD8+ cells proliferate
      after polyclonal stimulation of PBMC of children with atopic dermatitis.
AB  - BACKGROUND: Few studies describe in vitro food-allergen induced proliferative
      responses and cytokine production of PBMC of children with atopic dermatitis.
      This is especially true for peanut-allergen. OBJECTIVES: To analyse the
      specificity of the T cell in proliferative responses, in children with atopic
      dermatitis with or without peanut allergy and healthy age-matched children.
      METHODS: Proliferative responses were measured by [3H]-thymidine incorporation
      and by expression of the intracellular Ki67-antigen using flow cytometry after
      antigen-specific stimulation of PBMC with peanut-extract (day 7) or polyclonal
      stimulation with Phorbol-12myristate-13acetate and Ca-ionophore (day 3). Cytokine
      mRNA (Interferon-gamma (IFNgamma), IL-4) was detected by semiquantitative RT-PCR.
      Cytokine production (IL-4, IFNgamma) was measured by ELISA. RESULTS: Peanut
      extract induced proliferative responses of PBMC from children with atopic
      dermatitis and peanut allergy (AD+PA+) were significantly higher as compared with
      the other groups studied. Ki67-antigen double staining revealed that 80-100% of
      the proliferating cells were CD4+. These proliferative responses correlated
      significantly with the increase in IL-4 mRNA expression after peanut-extract
      specific stimulation. After polyclonal stimulation, however, CD8+ cells
      preferentially proliferated. The degree of proliferation after polyclonal
      stimulation correlated inversely with the ratio of IL-4/IFNgamma production.
      CONCLUSIONS: The principal responding population of T cells in proliferative
      responses is different after peanut-extract specific and polyclonal stimulation
      of PBMC from AD+PA+ patients. Furthermore, we found indirect evidence that the
      PBMC fraction of AD+PA+ children contains increased frequencies of peanut
      specific T helper-2 cells.

PMID- 9537778
TI  - Hymenoptera venom hypersensitivity: an update.

PMID- 9537779
TI  - Expression of the house dust mite allergen Der p 2 in the baker's yeast
      Saccharomyces cerevisiae.
AB  - BACKGROUND AND RESULTS: The major house dust mite allergen Der p 2 was expressed
      as a recombinant mature protein in the baker's yeast Saccharomyces cerevisiae.
      The yeast produces the protein fused to the invertase signal peptide, leading to
      the secretion of Der p 2 as a soluble protein into the culture medium. The signal
      peptide is hereby cleaved off, resulting in a mature allergen. In this system Der
      p 2 was produced in 7.6 (+/-2.9) mg/L growth culture. Purification of the
      recombinant allergen was achieved by a single gel filtration step, resulting in a
      purity > or = 95%. The yeast-derived Der p 2 was almost indistinguishable from
      natural Der p 2 with respect to IgE-reactivity and binding to the majority of Der
      p 2 specific MoAbs -- as was shown in RAST analysis (n = 168) and a sandwich
      ELISA and RIA analysis, respectively. Recombinant and natural Der p 2 also showed
      similar biological activity in histamine release assays (n = 4). CONCLUSION: An
      expression system for Der p 2 was developed that enables the production of a
      soluble allergen in the culture supernatant with immunological characteristics
      similar to the natural allergen. In addition, yeast offers the advantage of the
      absence of endotoxin in comparison to E. coli. This might facilitate acceptance
      of recombinant allergens for in vivo applications as immunotherapy or skin-prick
      testing.

PMID- 9537781
TI  - Mite control with low temperature washing-II. Elimination of living mites on
      clothing.
AB  - BACKGROUND: Allergens produced by mites are one of the principal causes of
      allergic disease. House dust mites can be found in significant numbers living in
      textile garments, and therefore development of optimal washing conditions for
      delicate textiles represents an important aim for domestic mite control.
      OBJECTIVES: Investigation of methods to eliminate house dust mites from clothing
      under low temperature washing conditions. METHODS: Domestic house dust mites
      Dermatophagoides farinae were cultured on garments under favourable conditions.
      The breeding success was monitored in terms of population and distribution using
      the free-mite Mobility Test. The mite containing garments were washed at low
      temperature with different commercial detergents in the presence or absence of a
      mite control additive containing 0.03% benzyl benzoate, and the numbers of mites
      surviving the washing process were assessed using the Heat Escape Method.
      RESULTS: The successful culture of mites in textile garments led to mite numbers
      of a total of at least 9000 to 10000 mites in 10 garments (Mobility Test). After
      washing in a domestic washing machine with detergents alone approximately 6000
      remaining mites were detected in 10 garment halfs (Heat Escape Method). In
      contrast, mite control by the application of the same detergents together with an
      additive achieved a reduction to almost 50 mites. This is an additional reduction
      in mite numbers of 99.2%. CONCLUSIONS: It is possible to achieve mite control in
      delicate garments by washing at low temperature in the presence of a mite control
      additive providing a final concentration of 0.03% benzyl benzoate.

PMID- 9537782
TI  - Changes in IgE-mediated allergy to ubiquitous inhalants after removal from or
      diminution of exposure to the agent causing occupational asthma.
AB  - BACKGROUND: One possibility, among others, for explaining the persistence of
      asthma symptoms in occupational asthma (OA) after the cessation of exposure to
      the causal agents may be that subjects become sensitized to ubiquitous inhalants.
      OBJECTIVE: The aim of this study was to evaluate the development or increase of
      IgE-mediated sensitization to ubiquitous allergens, both to high- and low
      molecular-weight agents, in 100 subjects with OA after cessation of exposure.
      METHODS: Subjects were evaluated on a first visit, at the time of diagnosis of
      OA, coinciding with the cessation or diminution of exposure to the causal agent,
      and on a second visit, 5.8+/-3.3 years afterwards. At each visit, a history of
      ocular, nasal and asthmatic symptoms related to exposure to common allergens was
      obtained together with spirometry and assessment of bronchial responsiveness to
      methacholine. We analysed total IgE and specific IgE to Dermatophagoides farinae,
      D. pteronyssinus, birch, ragweed and timothy grass pollens, cat and dog danders,
      and Alternaria, using enzyme allergosorbent test (EAST) from blood samples taken
      on each visit. RESULTS: Total IgE levels showed a tendency to diminish. No
      changes were found in the number of positive EAST (presence of detectable levels
      of specific IgE) or in the levels of specific IgE. Although significantly more
      symptoms of rhinoconjunctivitis and asthma in contact with house dust (P < 0.05)
      and pets (P < 0.01) were reported on the second visit than on the first, no
      significant changes in the frequency of symptomatic sensitized subjects were
      found. CONCLUSION: Subjects with OA are unlikely to develop IgE-dependent
      sensitization to common inhalants after removal from exposure to occupational
      agents.

PMID- 9537783
TI  - Immunological responses in peanut allergy.

PMID- 9537780
TI  - Domestic allergens in public places III: house dust mite, cat, dog and cockroach
      allergens in British hospitals.
AB  - BACKGROUND: Exposure and sensitization to indoor allergens is a major cause of
      asthma. OBJECTIVES: This study investigated the levels of house dust mite, cat,
      dog and cockroach allergens in the dust and air in hospitals and the effects of
      regular vacuum cleaning on allergen levels in hospital chairs. METHODS: Der p 1,
      Fel d 1, Can f 1 and Bla g 2 were measured in the dust collected by vacuuming
      upholstered chairs and a 1 m2 area of carpet and mattress in 14 hospitals. Air
      samples were collected using an air sampler (flow rate 60 L/min) on 10 separate
      days for 4 h in the outpatient department in one of the hospitals during busy
      clinics when patients were waiting for their appointments. In addition, dust
      samples were collected on four occasions, at 4-weekly intervals, from 36 fabric
      covered chairs in the outpatient area of a busy chest clinic by vacuuming each
      chair for 2 min. During the intervening weeks, 18 of the chairs (active group)
      were each cleaned by vacuuming for 1 min, three times per week. Der p 1, Fel d 1,
      Can f 1 and Bla g 2 were assayed using monoclonal antibody-based ELISA. RESULTS:
      In total, 83 carpets, 69 mattresses and 42 upholstered chairs were sampled. The
      levels of dust mite allergen Der p 1 and cockroach allergen Bla g 2 found in the
      hospital setting were low. High levels of Fel d 1 (GM 22.9 microg/g, range 4.5
      58) and Can f 1 (GM 21.6 microg/g, range 4-63) were found in upholstered chairs.
      Airborne Can f 1 was detected on every occasion (range 0.12-0.56 ng/m3), whilst
      detectable airborne Fel d 1 was found on 7 out of the 10 sampling days (range
      0.09-0.22 ng/m3). Der p 1 and Bla g 2 were below the detection limit in all
      airborne samples. Following repeated vacuuming the mean cat and dog allergen
      levels decreased significantly (P<0.001) and were almost fivefold lower in the
      vacuumed chairs compared with the control group. CONCLUSIONS: Low levels of mite
      allergen are unlikely to be of any clinical significance to mite-sensitive
      asthmatic patients. However, upholstered chairs in hospitals constitute a
      significant reservoir of cat and dog allergen. Inhalation of airborne allergen in
      patients attending their hospital appointment may exacerbate asthma in those
      highly allergic to cats or dogs. These results question the wisdom of introducing
      soft furnishings and carpets into hospitals. Three-times weekly vacuuming
      significantly reduces allergen levels in upholstered chairs.

PMID- 9537784
TI  - Serum IgE level is negatively correlated with the ability of peripheral
      mononuclear cells to produce interferon gamma (IFNgamma): evidence of reduced
      expression of IFNgamma mRNA in atopic patients.
AB  - BACKGROUND: In patients with atopic diseases such as bronchial asthma and atopic
      dermatitis, an elevated serum IgE level is common. Several studies showed that
      interleukin-4(IL-4) and interferon-gamma (IFNgamma) are important for regulation
      of IgE production. OBJECTIVES: The study was designed to examine the pathogenesis
      of an elevated serum IgE level at the production levels of TH1-type and TH2-type
      cytokines. METHODS: The production of interleukin-2 (IL-2), IL-4, interleukin-5
      (IL-5) and IFNgamma by peripheral blood mononuclear cells (PBMCs) stimulated with
      phytohemagglutinin (PHA) was analysed in 20 individuals with various serum IgE
      levels. The amount of IFNgamma mRNA in the stimulated PBMCs was analysed using a
      quantitative polymerase chain reaction method. RESULTS: Cytokine production was
      analysed simply as a function of serum IgE level. The serum IgE level was
      negatively correlated with the amount of IFNgamma secreted by PBMCs (n = 20, R = 
      0.724, P<0.005) when logarithmically transformed data were analysed, but were not
      or were only weakly correlated with those of IL-4, IL-2, or IL-5 secreted by
      these cells (n = 20). For investigation of the cause of reduced IFNgamma
      production in individuals whose serum IgE level are high, the amount of IFNgamma
      mRNA was determined. The levels of IFNgamma mRNA expression in the stimulated
      PBMCs correlated well with the amount of IFNgamma secreted by the PBMCs (n = 8, R
      = 0.947, P < 0.001). CONCLUSIONS: Reduced IFNgamma production ability due to
      reduced IFNgamma mRNA expression in PBMCs is associated with an elevated serum
      IgE level in atopic patients.

PMID- 9537785
TI  - Histamine and tryptase in nasal lavage fluid following challenge with
      methacholine and allergen.
AB  - BACKGROUND: The level of histamine in nasal lavage fluid has been used as an
      index of mast cell/basophil activation in a number of studies. Obviously, such an
      index can only be valid if changes in the secretory activity of nasal glands do
      not affect the level of histamine in lavage fluid (i.e. hypersecretion, without a
      simultaneous activation of mast cells/basophils in the nasal mucosa, must not
      increase the level of histamine). OBJECTIVES: To asses the effect of nasal
      hypersecretion on histamine levels in lavage fluid. METHODS: Nasal challenges
      were performed with methacholine and allergen in grass pollen-allergic patients
      and non-allergic controls. Nasal lavage fluid was collected before and repeatedly
      for nine hours after nasal challenge, and the level of histamine was compared
      with that of a specific mast cell-derived enzyme, tryptase. In addition, the
      effect of methacholine on basophils was examined in vitro. RESULTS: Allergen
      challenge of allergic patients produced sneezing and a significant increase in
      histamine and tryptase levels, whereas challenge of non-allergic subjects
      produced no such response. Interestingly, challenge with methacholine also
      induced a significant increase in histamine levels. This increase was seen in
      both allergic and non-allergic subjects and it was not associated with any
      sneezing or increase in tryptase levels, indicating that mast cells were not
      activated. Furthermore, stimulation of basophils with methacholine did not induce
      any histamine release in vitro. CONCLUSIONS: Apparently, there exists a pool of
      histamine in the human nose that can be transferred to lavage fluid during
      glandular hypersecretion. The source of this histamine is yet to be identified.
      As the level of histamine seems to be affected by the secretory activity of nasal
      glands, we question the use of this single mediator as an index of mast
      cell/basophil activation in nasal lavage studies.

PMID- 9537787
TI  - The Department of Biochemistry at the University of Dundee.

PMID- 9537786
TI  - Comparison of nasal mucosal responsiveness to neuronal stimulation in non
      allergic and allergic rhinitis: effects of capsaicin nasal challenge.
AB  - BACKGROUND: Neuronal involvement has been implicated in the pathophysiology of
      non-allergic and allergic rhinitis, contributing to the typical exacerbation of
      these conditions upon exposure to non-specific environmental irritants.
      OBJECTIVES: To determine if non-allergic and allergic rhinitis are characterized
      by increased responsiveness of the nasal mucosa to sensorineural stimulation.
      METHODS: Nasal challenges with capsaicin and its vehicle were performed in three
      groups of subjects -- non-allergic rhinitics, perennial allergic rhinitics, and
      healthy controls -- and resultant symptom scores, glandular secretion reflected
      by lactoferrin levels, and plasma extravasation reflected by albumin levels in
      nasal lavage fluid were compared. RESULTS: Capsaicin-sensitive nerve stimulation
      produced increases in symptom scores and lactoferrin levels which were similar
      among the three groups of subjects. On the other hand, only the group of subjects
      with allergic rhinitis demonstrated a significant capsaicin-induced increase in
      albumin levels and a trend in total protein levels. CONCLUSIONS: We conclude that
      non-allergic rhinitis is not characterized by increased responsiveness of
      capsaicin-sensitive nerve fibres; while allergic rhinitis is marked by
      hyperresponsiveness manifested as increased albumin leakage in nasal fluids. This
      may reflect the activity of an axonal reflex to sensorineural stimulation.

PMID- 9537788
TI  - Comparison of the degradation patterns of polychlorinated biphenyl congeners in
      Aroclors by Pseudomonas strain LB400 after growth on various carbon sources.
AB  - Resting cells of Pseudomonas strain LB400, grown on biphenyl, transformed 80, 50
      and 17% of Aroclor 1242, 1254, and 1260, respectively. Resting cells grown on
      glucose or glycerol also transformed these polychlorinated biphenyl (PCB)
      mixtures to the extent of 60, 35, and 9% for Aroclors 1242, 1254, and 1260,
      respectively. Time courses of the transformation of the separated individual
      congeners in the Aroclors were plotted and used to determine the transformation
      rate constants (k). By analysis of the rate constants, it was concluded that the
      order of degradation of the different congeners in an Aroclor were similar
      regardless of the growth substrate. In general, k values for the conversion of a
      particular congener were lower for cells grown on glucose or glycerol compared
      with cells grown on biphenyl. Generally, k values for the transformation of the
      same congener in different Aroclors were not the same: rate constants had highest
      values for the congener in Aroclor 1242 and lowest values in Aroclor 1260. The
      data allowed congeners to be grouped according to their relative rates of
      degradation. The ratio of k values for transformation of individual congeners in
      Aroclors by cells grown on biphenyl and glucose were not constant.

PMID- 9537789
TI  - 7th International Workshop on Chronic Lymphocytic Leukemia. Crete, Greece, May 2
      4, 1997. Proceedings and abstracts.

PMID- 9537791
TI  - [The clinical spectrum of the antiphospholipid syndrome].

PMID- 9537790
TI  - Quiz case of the month. Cerebral deep vein thrombosis.

PMID- 9537792
TI  - [In memoriam Aleksandra Konstantinovna Fedorova-Grot].

PMID- 9537793
TI  - Vascular pathogenesis of normal-tension glaucoma: a possible pathogenetic factor,
      other than intraocular pressure, of glaucomatous optic neuropathy.
AB  - Elevated intraocular pressure is significant in the pathogenesis of glaucomatous
      optic neuropathy in glaucoma, however a number of studies suggest that pressure
      independent factor(s) are also associated with the pathogenesis. In this article,
      the significance of vascular pathogenesis in glaucoma is discussed. A brief
      overview of substances used to treat glaucoma, independent of an effect on
      intraocular pressure, such as calcium channel blockers, is also discussed.

PMID- 9537794
TI  - Ophthalmic drug delivery systems--recent advances.
AB  - Eye-drops are the conventional dosage forms that account for 90% of currently
      accessible ophthalmic formulations. Despite the excellent acceptance by patients,
      one of the major problems encountered is rapid precorneal drug loss. To improve
      ocular drug bioavailability, there is a significant effort directed towards new
      drug delivery systems for ophthalmic administration. This chapter will focus on
      three representative areas of ophthalmic drug delivery systems: polymeric gels,
      colloidal systems, cyclodextrins and collagen shields. Hydrogels generally offer
      a moderate improvement of ocular drug bioavailability with the disadvantage of
      blurring of vision. In situ activated gel-forming systems are preferred as they
      can be delivered in drop form with sustained release properties. Colloidal
      systems including liposomes and nanoparticles have the convenience of a drop,
      which is able to maintain drug activity at its site of action and is suitable for
      poorly water-soluble drugs. Among the new therapeutic approaches in
      ophthalmology, cyclodextrins represent an alternative approach to increase the
      solubility of the drug in solution and to increase corneal permeability. Finally,
      collagen shields have been developed as a new continuous-delivery system for
      drugs that provide high and sustained levels of drugs to the cornea, despite a
      problem of tolerance. It seems that new tendency of research in ophthalmic drug
      delivery systems is directed towards a combination of several drug delivery
      technologies. There is a tendency to develop systems which not only prolong the
      contact time of the vehicle at the ocular surface, but which at the same time
      slow down the elimination of the drug. Combination of drug delivery systems could
      open a new directive for improving results and the therapeutic response of non
      efficacious systems.

PMID- 9537795
TI  - Electrical responses from diabetic retina.
AB  - Diabetic retinopathy has long been considered to be a retinal manifestation of
      systemic diabetic angiopathy. Indeed, it is therapeutically true. However, the
      prolongation of OP peak latency in diabetic eyes without any angiographic
      evidence of angiopathy leads us to presume that certain neuronal disorders occur
      early in diabetic eyes. Even though we cannot neglect the possibility that the
      prolongation of the OP peak latency may derive from undetectable retinal
      hypoperfusion, it is still far from conventional diabetic angiopathy. Rather, the
      status should be properly termed "intraretinal diabetic neuropathy" in that the
      neurones are the disturbed cells to cause visual dysfunction. Thereafter, the OP
      amplitude diminishes as retinopathy advances, probably depending on the degree of
      retinal circulatory disturbance. Marked diminution of the OP amplitude predicts
      rapid progression and poor prognosis of retinopathy. Diabetic retinal pigment
      epitheliopathy as manifested by one of our non-photic EOG responses is another
      kind of early ocular involvement of diabetes. Because its mechanisms are not yet
      known, so far we have not succeeded in correlating it to any kind of subjective
      visual index. Routine fundus inspection or fluorescent fundus angiography is
      incapable of detecting the compromised neural retina and/or retinal pigment
      epithelial integrity and thus the electrophysiology of vision has the edge in
      ophthalmology.

PMID- 9537796
TI  - Risk factors for proliferative vitreoretinopathy.
AB  - Proliferative vitreoretinopathy (PVR) is one of the major causes of failure in
      retinal detachment surgery. To prevent PVR, it is necessary to determine factors
      predisposing its development. In primary PVR, large retinal tears, long duration
      of retinal detachment, vitreous hemorrhages, aphakia and choroidal detachment
      were demonstrated as clinical risk factors for PVR. In postoperative PVR, it was
      revealed that large breaks, pre- and postoperative choroidal detachment, minor
      intra- or postoperative hemorrhages, signs of uveitis, extensive retinal
      detachment, vitrectomy, cryopexy, air injection and preoperative PVR were risk
      factors for PVR by multivariate analysis. Almost all risk factors for PVR are
      associated with intravitreal dispersion of retinal pigment epithelial (RPE) cells
      or breakdown of the blood-ocular barrier which are prerequisite to development of
      PVR.

PMID- 9537797
TI  - Xerophthalmia and vitamin A status.
AB  - The existence of 'fat-soluble A' has been known for over 80 years. But until
      recently clinicians were almost wholly absorbed by the ocular changes
      accompanying deficiency (xerophthalmia), and scientists with the vitamin's
      metabolic role in the rhodopsin cycle. The past two decades have witnessed a
      revolution in clinical and scientific concerns. Xerophthalmia is now recognized
      as a late manifestation of severe deficiency rather than of early, mild
      deficiency; as the mechanism responsible for half or more of all measles
      associated blindness; and as the cause of half a million or more cases of
      pediatric blindness worldwide. Milder deficiency increases the severity of
      infectious morbidity, exacerbates iron deficiency anemia, retards growth, and is
      responsible for one to three million childhood deaths each year. Scientists are
      now busy unraveling vitamin A-dependent gene regulation to explain the myriad
      manifestations accompanying deficiency, while clinicians are designing and
      supervising programs to improve vitamin A status in over 60 countries, up from
      only three countries two decades ago. Control of vitamin A deficiency is now a
      major health challenge and goal of both UNICEF and the World Health Organization
      (WHO). Reaching that goal requires better parameters for assessing vitamin A
      status, increased understanding of metabolic pathways responsible for corneal
      dissolution (keratomalacia) and the molecular and cellular basis by which vitamin
      A status mediates resistance to infection. These issues are detailed elsewhere
      (Sommer and West, 1996).

PMID- 9537798
TI  - GABA-gated Cl- channels in the rat retina.
AB  - gamma-Aminobutyric acid (GABA) is a major inhibitory neurotransmitter in the
      mammalian retina, and its physiological action is well established. GABA
      receptors have been localized immunocytochemically in the retina of different
      mammalian species, and all major retinal cell types have been found to express
      GABAA receptor subunits. Recently, a new type of GABA receptor with
      pharmacological and electrophysiological properties different from the known
      GABAA and GABAB receptors, has been described. These GABAC receptors are found
      predominantly in the vertebrate retina. This review concentrates on the
      electrophysiological characterization of GABA receptors expressed by amacrine and
      bipolar cells of the rat retina. We recorded GABA-induced currents from cultured
      neonatal amacrine and bipolar cells as well as from isolated bipolar cells of
      adult animals. While amacrine cells contain a homogeneous population of GABAA
      receptors, bipolar cells exhibit both GABAA and GABAC responses. Although both
      receptors gate chloride-selective ion channels, their biophysical and
      pharmacological properties differ markedly. These functional differences and the
      cellular distribution of GABAA and GABAC receptors suggest that they have
      different inhibitory functions in the rat retina.

PMID- 9537799
TI  - [Laparoscopic colorectal surgery].

PMID- 9537800
TI  - Proceedings of the International Conference on Radiation and Health. Beer Sheva,
      Israel, 3-7 November 1996.

PMID- 9537801
TI  - Wash-out kinetics of 99mTc-MIBI and the scintigraphic determination of Pgp
      expression: reply.

PMID- 9537802
TI  - Ca2+ channel inhibition by endomorphins via the cloned mu-opioid receptor
      expressed in NG108-15 cells.
AB  - Endomorphin-1 and -2, recently isolated endogenous peptides specific for the mu
      opioid receptor, inhibited Ca2+ channel currents with EC50 of 6 and 9 nM,
      respectively, in NG108-15 cells transformed to express the cloned rat mu-opioid
      receptor. On the other hand, they elicited no response in nontransfected NG108-15
      cells. It is concluded that endomorphin-1 and -2 induce Ca2+ channel inhibition
      by selectively activating the mu-opioid receptor.

PMID- 9537803
TI  - A single dose of methamphetamine in neonatal gerbils affects adult prefrontal
      gamma-aminobutyric acid innervation.
AB  - A single non-invasive dose of methamphetamine (50 mg/kg i.p.) was administered to
      neonatal male gerbils (Meriones unguiculatus) aged 14 days. At the age of
      postnatal day 90, the gamma-aminobutyric acid (GABA) immunoreactive profiles were
      electron microscopically quantified in the prelimbic area of the prefrontal
      cortex and compared with those of saline-treated controls. This early solitary
      drug challenge resulted in adult GABAergic innervation densities which were
      approximately 40% above those of saline-treated controls.

PMID- 9537804
TI  - Inhibition of intestinal motility by anandamide, an endogenous cannabinoid.
AB  - The endogenous cannabinoid ligand anandamide (arachidonylethanolamide) inhibited
      the intestinal passage of a charcoal meal when administered s.c. in mice at doses
      ranging from 0.1 to 50 mg/kg. This effect was prevented by the cannabinoid CB1
      receptor antagonist SR141716A [N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4
      dichlorophenyl)-4-me thyl-1H-pyrazole-3-carboxamide x HCl] (1 mg/kg s.c.), but it
      was not affected by the anandamide transport inhibitor, N-(4-hydroxyphenyl)
      arachidonylethanolamide (AM404) (50 mg/kg, s.c.). The results indicate that
      anandamide modulates intestinal motility in mice by activating cannabinoid CB1
      receptors. They also suggest that anandamide transport, which was previously
      shown to participate in terminating neural and vascular responses to anandamide,
      does not contribute to anandamide inactivation in intestinal tissue.

PMID- 9537805
TI  - Effects of ondansetron administration on opioid withdrawal syndrome observed in
      rats.
AB  - This study tested whether a 5-HT3 receptor antagonist could reverse the signs of
      precipitated opioid withdrawal. Rats were treated with either saline or morphine
      for 4 days. After the four days, half of the rats in each group received naloxone
      and half received saline. Each animal also received one of four doses of
      ondansetron (0, 1, 2 and 4 mg/kg i.p.). Administration of ondansetron to rats
      receiving naloxone after chronic morphine decreased the intensity of withdrawal
      signs such as increased defecation, jumping and wet-dog shakes, elevated the
      nociceptive threshold values which were decreased by precipitated withdrawal, but
      produced no change in urination, rectal temperature or salivation. The effects
      exhibited by ondansetron administration may be explained through interference of
      its 5-HT3 receptor antagonist activity with serotoninergic mechanisms involved in
      the regulation of these withdrawal symptoms. The use of this drug is thus
      suggested as a possible treatment of opioid withdrawal signs in heroin addicts.

PMID- 9537806
TI  - Anti-anhedonic actions of the novel serotonergic agent flibanserin, a potential
      rapidly-acting antidepressant.
AB  - Chronic exposure to mild unpredictable stress has previously been found to
      depress the consumption of palatable sweet solutions and to block the formation
      of conditioned place preferences; these effects are reversed by chronic treatment
      with tricyclic or atypical antidepressant drugs. The present study was designed
      to evaluate the antidepressant-like activity in this model of flibaserin (BIMT
      17), a novel serotonergic agent with 5-HT1A receptor agonist and 5-HT2 receptor
      antagonist properties. Two experiments were conducted, using rats (experiment 1)
      and mice (experiment 2). In experiment 1, decreases in sucrose intake were seen
      in rats exposed to chronic mild stress, but the effect was unreliable in this
      study, and sucrose testing was terminated after 7 weeks of stress. Beginning
      after 5 weeks of stress, groups of control and stressed animals were treated
      daily with vehicle, fluoxetine (5 mg/kg) or flibanserin (5, 10 or 20 mg/kg).
      After 6 weeks of treatment, all animals were tested for acquisition of food
      reinforced place preference conditioning. Conditioning was seen in all groups
      other than the vehicle-treated stressed animals. We also tested the locomotor
      stimulant effect of a single injection of the dopamine D2/D3 receptor agonist
      quinpirole (0.2 mg/kg). The effect of quinpirole was potentiated by fluoxetine in
      control animals, and by both fluoxetine and flibanserin (all doses) in stressed
      animals. In experiment 2, long-lasting decreases in sucrose intake were seen in
      mice exposed to chronic mild stress. The effects were reversed by chronic (4
      weeks) treatment with fluoxetine (5 mg/kg) or flibanserin (2.5 or 5 mg/kg); the
      full effect of flibanserin was seen after the first injection. All animals
      received a single injection of raclopride (0.1 mg/kg) immediately prior to a
      sucrose intake test on day 27 of drug treatment. Raclopride decreased sucrose
      intake only in the three drug-treated stressed groups. The results support a
      rapid antidepressant-like action of flibanserin, and suggest that this effect
      involves sensitization of dopamine D2/D3 receptor-mediated transmission.

PMID- 9537807
TI  - Characteristics of the NMDA receptor modulating hypoxia/hypoglycaemia-induced rat
      striatal dopamine release in vitro.
AB  - We investigated the functional characteristics of the NMDA receptor that
      modulates hypoxia/hypoglycaemia-induced striatal dopamine release. Dopamine
      release was detected by fast cyclic voltammetry in rat neostriatal slices. Four
      variables were measured: T(on) -- time from initiation of hypoxia/hypoglycaemia
      to the onset of dopamine release, Tpk -- time from onset to maximum,
      deltaDA/delta(t) -- rate of dopamine release and DAmax -- maximum extracellular
      dopamine concentration. In controls, T(on) = 164.9 +/- 1.7 s, Tpk = 20.9 +/- 0.9
      s, deltaDA/delta(t) = 5.31 +/- 0.44 microM/s and DAmax = 79.1 +/- 2.5 microM
      (means +/- S.E.M., n = 203). Cis-4-(phosphonomethyl)piperidine-2-carboxylic acid
      (CGS 19755, 20 microM) lengthened, while N-methyl-D-aspartate (NMDA) (100 microM)
      shortened T(on). (5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten
      5,1 0-imine hydrogen maleate (MK 801, 1 and 10 microM) and dextromethorphan (10
      and 100 microM) increased Tpk and decreased DAmax. Neither glycine (100 microM),
      7-chlorokynurenic acid (50 microM) nor 5-nitro-6,7-dichloro-1,4
      dihydroquinoxaline-2,3-dione (ACEA 1021, 100 microM) had any effect although 7
      chlorokynurenic acid blocked the effect of NMDA. Increasing [Mg2+] from 1.3 to
      3.7 mM, increased Tpk and decreased deltaDA/delta(t). Dithiothreitol (1 mM)
      accelerated T(on) while 5.5-dithio-bis-(2-nitrobenzoic acid) (1 mM) delayed
      T(on). Neither drug affected Tpk, DAmax or deltaDA/delta(t). Neither spermidine
      (100 microM) nor arcaine (100 microM) affected T(on), Tpk or deltaDA/delta(t)
      although arcaine decreased DAmax. In conclusion, hypoxia/hypoglycaemia-induced
      dopamine release was influenced by an NMDA receptor although modulation of the
      glycine recognition site of the receptor was ineffective, as were agents acting
      at polyamine modulatory zones. These findings highlight differences between
      recombinant and native NMDA receptors and suggest caution in extrapolating
      molecular biology to functional studies.

PMID- 9537808
TI  - Effect of quinine on autoreceptor-regulated serotonin release in the rat
      hippocampus.
AB  - The involvement of K+ channels in the autoregulation of terminal serotonin (5
      hydroxytryptamine, 5-HT) release was investigated by microdialysis in the
      hippocampus of conscious rats. Extracellular 5-HT was increased concentration
      dependently by the K+ channel blocker quinine (10, 100 and 1000 microM in
      perfusate), and tetrodotoxin (10 microM) but not fluoxetine (5 microM) exerted a
      partially attenuating influence. The 5-HT1/2/6 receptor antagonist methiothepin
      (50 microM) increased dialysate 5-HT, most likely through 5-HT1B autoreceptors
      tonically activated in the hippocampus of awake rats as opposed to the previously
      reported lack of effect 5-HT1B autoreceptor blockade in anesthetized rats. The
      effect of methiothepin was greatly reduced by preperfusion with quinine (100
      microM), consonant with a role for quinine-sensitive K+ channels in the
      autoregulation of 5-HT release in the hippocampus by 5-HT receptor antagonism. In
      contrast, the reduction in dialysate 5-HT induced by the 5-HT1 receptor agonist
      RU 24969 (1 microM), in the presence of fluoxetine (5 microM), persisted in the
      co-presence of quinine, consonant with the involvement of (extrasynaptic?) 5-HT
      autoreceptors not coupled with quinine-sensitive K+ channels.

PMID- 9537809
TI  - Differential changes in induced seizures after hippocampal treatment of rats with
      an antisense oligodeoxynucleotide to the GABA(A) receptor gamma2 subunit.
AB  - Gamma-aminobutyric acid (GABA) is the principal inhibitory neurotransmitter in
      the brain. Impairment of GABAergic neurotransmission may be involved in the
      pathogenesis of epileptic phenomena. We have previously characterized biochemical
      and histological changes following unilateral intrahippocampal infusion of a
      phosphorothioate antisense oligodeoxynucleotide to the GABA(A) receptor gamma2
      subunit in rats in vivo. The aim of the present study was to investigate the
      behavioral changes of rats following unilateral hippocampal antisense 'knockdown'
      of the GABA(A) receptor gamma2 subunit. Antisense, but not mismatch control
      oligodeoxynucleotide treated rats had a significant weight loss (10%) during 6 d
      of treatment. Antisense treated rats exhibited no changes in spontaneous
      behavior, including anxiety-like behavior as measured in the social interaction
      test, compared to mismatch oligodeoxynucleotide treated rats. However, antisense
      treated rats developed pronounced changes in induced seizure activity. Seizures
      induced by subcutaneously injected pentylenetetrazol were markedly accentuated in
      antisense treated rats compared to treatment naive rats, whereas mismatch treated
      rats showed a lower seizure score than that of naive rats. Antisense treated rats
      had a significantly elevated threshold for seizures induced by electrical
      stimulation in the maximal electroshock seizure threshold test. The results
      suggest that intrahippocampal infusion of antisense oligodeoxynucleotide to the
      GABA(A) receptor gamma2 subunit leads to specific alterations in the sensitivity
      to induced seizures. The results are viewed as consequences of selective down
      regulation of GABA(A) receptors and diminished inhibitory neurotransmission in
      the hippocampus.

PMID- 9537810
TI  - Characterization of neonatal rat morphine tolerance and dependence.
AB  - The administration of morphine and fentanyl by continuous intravenous infusion
      has been shown to produce analgesic tolerance and physical dependence in human
      neonates. In animals, daily repeated morphine bolus injections is a common method
      of inducing neonatal rat tolerance and dependence. Yet this method differs from
      the intravenous route reported to affect human neonates. Alzet osmotic minipumps
      were implanted in postnatal day 14 rats to provide a continuous morphine infusion
      more closely mimicking the clinical picture. Rats remained naive or were infused
      with saline or morphine (0.7 mg/kg/h) for 72 h. Morphine's antinociceptive
      potency was similar between naive and saline-infused animals, while morphine
      infused animals were tolerant. Gender did not contribute to the degree of
      tolerance observed. Naloxone precipitated withdrawal in the morphine pump
      implanted rats was similar to that reported by others. Thus, minipumps provide a
      useful model for assessing the tolerance and dependence liability of different
      opioids.

PMID- 9537811
TI  - Glucose deprivation increases basal and electrically evoked transmitter release
      from rat striatal slices. Role of NMDA and adenosine A1 receptors.
AB  - We have investigated how glucose deprivation in vitro influences the basal and
      electrically evoked release of dopamine and acetylcholine from rat striatal
      slices and the role of endogenous activation of NMDA receptors and adenosine A1
      receptors in determining the magnitude of this response. Rat striatal slices,
      preincubated with [3H]dopamine and [14C]choline, were superfused continuously and
      stimulated electrically. Before and during the second stimulation, some slices
      were superfused with glucose-free Krebs' solution. Such glucose deprivation
      caused a 2 to 3-fold increase of the electrically evoked, calcium-dependent
      release of endogenous adenosine (but not hypoxanthine and inosine) and
      [3H]dopamine and a 30% increase in release of [14C]acetylcholine. Glucose
      deprivation also caused a delayed increase in the release of [3H]dopamine, but
      not of [14C]acetylcholine. The dopamine release was not calcium dependent. The
      addition of 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 1 microM), a selective
      adenosine A1 receptor antagonist, slightly enhanced the glucose deprivation
      induced stimulatory effect on the evoked release of these two transmitters,
      whereas the NMDA receptor antagonist dizocilpine((+)-5-methyl-10,11-dihydro-5H
      dibenzo[a,d] cyclohepten-5,10-imine; 3 microM) markedly attenuated the
      stimulatory effect of glucose deprivation. The change in basal dopamine release
      was not influenced by DPCPX, but was slightly attenuated by dizocilpine. In
      summary, the results suggest that lack of substrate induces release of both
      glutamate, which by actions on presynaptic NMDA receptors causes the release of
      dopamine, and of adenosine, which via adenosine A1 receptors reduces the
      electrically evoked release of both dopamine and acetylcholine.

PMID- 9537812
TI  - Evidence for the involvement of the nitric oxide-cGMP pathway in the
      antinociception of morphine in the formalin test.
AB  - The effect of inhibition of nitric oxide synthesis and guanylate cyclase on the
      peripheral antinociceptive effect of morphine was assessed by using the formalin
      test in the rat. Saline, N(G)-monomethyl-L-arginine, a nitric oxide synthesis
      inhibitor (50 microg) and methylene blue, a guanylate cyclase inhibitor (500
      microg), did not exhibit any antinociceptive activity. However, morphine (10
      microg) produced a significant antinociceptive effect in phases 2a and 2b, which
      was reduced by pretreatment with either N(G)-monomethyl-L-arginine or methylene
      blue. These results suggest that the local administration of morphine induces
      antinociception by the activation of the L-arginine-nitric oxide-cGMP pathway.

PMID- 9537813
TI  - Effect of hydroxocobalamin on vasodilatations to nitrergic transmitter, nitric
      oxide and endothelium-derived relaxing factor in guinea-pig basilar artery.
AB  - In endothelium-denuded guinea-pig isolated basilar artery preparations,
      hydroxocobalamin (30, 100 and 300 microM) concentration-dependently inhibited the
      vasodilator responses to exogenous nitric oxide (NO), whereas the vasodilator
      responses to nitrergic nerve stimulation were slightly reduced by high (100 and
      300 microM) but not by the low (30 microM) concentration of hydroxocobalamin.
      Vasodilatation in response to sodium nitroprusside (10-100 nM) was totally
      abolished by 300 microM hydroxocobalamin. In endothelium-intact preparations,
      vasodilator responses to acetylcholine (0.3-3 microM) were significantly reduced
      or abolished by hydroxocobalamin (30-300 microM). The mean reduction by
      hydroxocobalamin of relaxations to acetylcholine was significantly greater than
      that of the equivalent response evoked by nitrergic nerve stimulation. The
      findings suggest that the nitrergic transmitter in the guinea-pig basilar artery
      may be quantitatively less susceptible than the endothelium-derived relaxing
      factor to the NO scavenger hydroxocobalamin.

PMID- 9537814
TI  - Differential effects of glibenclamide on responses to thromboxane A2 mimic,
      U46619, in the pulmonary and hindquarters vascular beds of the cat.
AB  - The inhibitory effects of the oral sulfonylurea, glibenclamide, on
      vasoconstrictor responses to the thromboxane A2 mimic, U46619, were investigated
      in the pulmonary and hindquarters vascular beds of the cat under constant flow
      conditions. When lobar arterial tone was at resting conditions (14 +/- 2 mm Hg),
      intralobar injections of U46619, prostaglandin F2alpha, prostaglandin D2,
      angiotensin II, norepinephrine, and BAY K 8644 caused dose-related increases in
      lobar arterial pressure without altering left atrial pressure. Following an
      intralobar infusion of glibenclamide (5 mg/kg), vasoconstrictor responses to
      U46619, prostaglandin F2alpha and prostaglandin D2 were significantly reduced,
      whereas vasoconstrictor responses to norepinephrine and angiotensin II were not
      altered and responses to BAY K 8644 were significantly enhanced. When tone in the
      pulmonary vascular bed was raised to a high steady level (36 +/- 3 mm Hg),
      glibenclamide in a dose of 5 mg/kg i.a. markedly attenuated responses to
      injections of U46619 and reduced the vasodilator responses to the K+-ATP channel
      opener, levcromakalim, whereas responses to acetylcholine and S-nitroso-N
      acetylpenicillamine (SNAP), a nitric oxide donor, were not changed. In the
      hindquarters vascular bed of the cat, administration of glibenclamide in a dose
      of 5 mg/kg i.a. had no significant effect on vasoconstrictor responses to U46619,
      norepinephrine or angiotensin II. Hindquarters vasodilator responses to
      levcromakalim, but not to nitric oxide, were decreased significantly following
      administration of glibenclamide. These data suggest that glibenclamide, in
      addition to inhibiting K+-ATP channels, has thromboxane A2 receptor blocking
      activity in the pulmonary vascular bed of the cat. These data also suggest that
      vasoconstrictor responses to U46619 may be mediated by different thromboxane A2
      receptors with different binding affinities in the pulmonary and in the
      hindquarters vascular beds of the cat.

PMID- 9537815
TI  - Mechanism of prostaglandin E2-, F2alpha- and latanoprost acid-induced relaxation
      of submental veins.
AB  - The mechanism of prostaglandin E2-, prostaglandin F2alpha- and latanoprost acid
      (13,14-dihydro-17-phenyl-18,19,20-trinor-prostaglandin F2alpha)-induced
      relaxation of the rabbit submental vein was studied. Prostaglandin E2 caused
      maximum relaxation of endothelin-1 precontracted vessels (EC50: 1.8 x 10(-8) M).
      Much of the relaxation could be abolished by denuding the endothelium with the
      nitric oxide synthase inhibitor, L-NAME (N(G)-Nitro-L-arginine methylester). CGRP
      (8-37) (calcitonin gene-related peptide fragment (8-37)), a calcitonin gene
      related peptide receptor antagonist, exhibited a partial blocking effect, whereas
      the tachykinin NK1 receptor blocker, GR 82334 ([D-Pro9[Spiro-gamma
      Lactam]Leu10,Trp11]physalaemin (1-11)), markedly attenuated the response. Both
      prostaglandin F2alpha and the relatively selective FP receptor agonist,
      latanoprost acid, caused relaxation of the veins to about 50% of the
      precontracted state in the presence of GR 32191B ([1R
      [1alpha(Z),2beta,3beta,5alpha]]-(+)-7-[5-([1,1'-b iphenyl]-4-ylmethoxy)-3-hydroxy
      2-(1-piperidinyl)cyclopentyl]-4-he ptenoic acid), a thromboxane receptor
      antagonist (EC50: for prostaglandin F2alpha 7.9 x 10(-9) M, and for latanoprost
      acid 4.9 x 10(-9) M). L-NAME, as well as denuding the endothelium, completely
      abolished the effect. In addition, most or at least a large part of the
      relaxation was also blocked by CGRP-(8-37) as well as GR 82334. These results
      indicate that the FP receptor-mediated relaxation of veins is based on release of
      nitric oxide in addition to involvement of calcitonin gene-related peptide and
      substance P, or some other tachykinin, probably released from perivascular
      sensory nerves. The more pronounced relaxation induced by prostaglandin E2 could
      be due to vasodilator EP receptors in the smooth muscle layer of the veins.

PMID- 9537816
TI  - Intracellular Ca2+ elevation and contraction due to prostaglandin F2alpha in rat
      aorta.
AB  - Prostaglandin F2alpha was tested to determine (a) whether its effect on
      intracellular Ca2+ levels ([Ca2+]i) and force in vascular smooth muscle was
      mediated through activation of the thromboxane A2 and/or prostaglandin receptor,
      and (b) the relative roles of Ca2+ influx via L-type and non-L-type Ca2+ channels
      in prostaglandin receptor-mediated contraction. [Ca2+]i and force were measured
      simultaneously in fura-2-loaded rat aortic strips. The thromboxane A2 receptor
      antagonist, SQ29548 ([1S]-1a,2b(5Z),3b,4a-7-(3-[2-[(phenylamino)carbonyl]
      hydrazinomethyl)-7-oxobicyclo-[2.2.1]hept-2-yl-5-heptenoic acid), prevented the
      prostaglandin F2alpha-induced plateau [Ca2+]i elevation and force by 80-90%,
      while abolishing these responses due to the thromboxane A2 receptor agonist,
      U46619 (9,11-dideoxy-9alpha,11alpha-methanoepoxy prostaglandin F2alpha).
      Prostaglandin F2alpha (+ SQ29548)-induced plateau [Ca2+]i elevation and force
      were not inhibited by verapamil. Ni2+, a non-selective cation channel blocker, in
      the presence of verapamil, abolished the prostaglandin F2alpha (+ SQ29548)
      elevated [Ca2+]i, while the contraction was only partially inhibited. These
      results suggest that, in rat aorta, (1) elevated [Ca2+]i and force due to high
      prostaglandin F2alpha concentrations largely results from thromboxane A2 receptor
      activation, and (2) the prostaglandin component of the prostaglandin F2alpha
      induced contraction is dependent on Ca2+ influx via non-L-type channels.

PMID- 9537817
TI  - Platelets enhance contractility in perfused rat mesenteric arteries: involvement
      of endothelin-1.
AB  - We investigated the effects of platelet supernatant on pressor responses to
      norepinephrine in isolated perfused rat mesenteric arteries. Perfusion of the
      arteries with platelet supernatant for 2 h markedly enhanced the pressor
      responses to norepinephrine (10(-6) and 3 x 10(-6) M). This enhancement was
      significantly inhibited by phosphoramidon (10(-4) M), an endothelin converting
      enzyme inhibitor. Both BQ788 [N-cis-2,6-dimethylpiperidinocarbonyl-L-gamma
      methylleucyl-D -1-methoxycarbonyltryptophanyl-D-norleucine] (10(-6) M), an
      endothelin ET(B) receptor antagonist, and bosentan (Ro47-0203, 4-tert-butyl-N-[6
      (2-hydroxy-ethoxy)-5-(2-methoxy-phenoxy)-2,2-bipyri midin-4-yl]
      benzenesulfonamide) (10(-5) M), a nonselective endothelin receptor antagonist,
      also prevented the potentiation of responses to norepinephrine evoked by platelet
      supernatant, but FR 139317 ((R)2-[(R)-2-[(S)-2-[[1-(hexahydro-1H
      azepinyl)]carbonyl]amino-4-+ ++methylpentanoyl] amino-3-[3-(1-methyl-1H
      indoyl)]propionyl]amino-3-(2-pyridyl) propionic acid) (10-6 M), an endothelin
      ET(A) receptor antagonist, had little effect. Suppressor doses of endothelin-1 (3
      x 10(-10) M) or sarafotoxin S6c (S6c) (3 x 10(-10) M) potentiated significantly
      the norepinephrine-induced vasoconstriction, in the same preparation. Moreover,
      supernatant-induced enhancement of pressor responses to norepinephrine was
      markedly suppressed by TGF-beta1 neutralizing antibody. Transforming growth
      factor-beta1 (TGF-beta1) (40 pM) also significantly enhanced the pressor
      responses to norepinephrine (10(-6) M) and this enhancement was significantly
      inhibited by phosphoramidon. These results suggest that platelet-derived TGF
      beta1 stimulates the vascular production of endothelin-1 and thereby enhances
      vasoconstrictor responses to norepinephrine. Platelet-induced enhancement of
      vasoconstrictor responses to norepinephrine seems to be mainly mediated by
      endothelin ET(B) receptor, in rat mesenteric arteries.

PMID- 9537818
TI  - Effects of a 5-HT1A receptor agonist on acute and delayed cyclophosphamide
      induced vomiting.
AB  - LY228729 [(-)-4(dipropylamino)-1,3,4,5-tetrahydrobenz-[c,d]indole-6-carboxa
      mide]], an agonist at the 5-HT1A subtype of 5-HT receptor, was studied as an
      antiemetic in pigeons dosed with a highly emetic oncolytic agent,
      cyclophosphamide. An intramuscular injection of 0.32 mg/kg of LY228729
      administered 15 min prior to the intravenous injection of 200 mg/kg of
      cyclophosphamide totally prevented the acute emetic response induced by
      cyclophosphamide. When used as a rescue therapy in a separate group of pigeons,
      LY228729 (0.32 mg/kg, i.m.) prevented further emetic episodes when it was
      administered after vomiting had already been induced by cyclophosphamide.
      Injections of LY228729 given at intervals over the next 2 d also attenuated the
      delayed emetic response induced by cyclophosphamide. LY228729 appears to be a
      broad spectrum antiemetic agent that is effective against the anticipatory, the
      acute and the delayed stages of emesis induced by oncolytic agents.

PMID- 9537819
TI  - Increased hypothalamic neuropeptide Y concentration or hyperphagia in
      streptozotocin-diabetic rats are not mediated by glucocorticoids.
AB  - Hypothalamic neuropeptide Y containing neurones are overactive and may mediate
      hyperphagia in insulin-deficient diabetic rats, but the factors stimulating them
      remain uncertain. To determine the possible role of glucocorticoids, we
      investigated the effects of the glucocorticoid receptor blocker mifepristone
      (RU486) on food intake and regional hypothalamic neuropeptide Y concentrations in
      streptozotocin-diabetic rats. RU486 (30 mg/kg) or corn oil vehicle control was
      given orally for 3 weeks to diabetic rats. Food intake and neuropeptide Y levels
      in the hypothalamic arcuate and paraventricular nuclei were increased in
      untreated diabetic rat groups (P < 0.01), and though RU486 did increase plasma
      corticosterone levels (P < 0.01) it did not have any effect on either feeding or
      neuropeptide Y levels (P = NS). These negative findings suggest that
      glucocorticoids may not be responsible for increasing hypothalamic neuropeptide Y
      or for hyperphagia in insulin-deficient diabetes.

PMID- 9537820
TI  - Molecular cloning and characterization of the four rat prostaglandin E2
      prostanoid receptor subtypes.
AB  - We have characterized the rat prostanoid EP1, EP2, EP3alpha and EP4 receptor
      subtypes cloned from spleen, hepatocyte and/or kidney cDNA libraries. Comparison
      of the deduced amino acid sequences of the rat EP receptors with their respective
      homologues from mouse and human showed 91% to 98% and 82% to 89% identity,
      respectively. Radioreceptor binding assays and functional assays were performed
      on EP receptor expressing human embryonic kidney (HEK) 293 cells. The KD values
      obtained with prostaglandin E2 for the prostanoid receptor subtypes EP1, EP2,
      EP3alpha and EP4 were approximately 24, 5, 1 and 1 nM, respectively. The rank
      order of affinities for various prostanoids at the prostanoid receptor subtypes
      EP2, EP3alpha and EP4 receptor subtypes was prostaglandin E2 = prostaglandin E1 >
      iloprost > prostaglandin F2alpha > prostaglandin D2 > U46619. The rank order at
      the prostanoid EP1 receptor was essentially the same except that iloprost had the
      highest affinity of the prostanoids tested. Of the selective ligands, butaprost
      was selective for prostanoid EP2, M&B28767 and sulprostone were selective for
      EP3alpha and enprostil displayed dual selectivity, interacting with both
      prostanoid receptor subtypes EP1 and EP3alpha. All four receptors coupled to
      their predominant signal transduction pathways in HEK 293 cells. Notably, using a
      novel aequorin luminescence assay to monitor prostanoid EP1 mediated increases in
      intracellular calcium, both iloprost and sulprostone were identified as partial
      agonists. Finally, by Northern blot analysis EP3 transcripts were most abundant
      in liver and kidney whereas prostanoid EP2 receptor mRNA was expressed in spleen,
      lung and testis and prostanoid EP1 receptor mRNA transcripts were predominantly
      expressed in the kidney. The rat prostanoid EP1 probes also detected additional
      and abundant transcripts present in all the tissues examined. These were found to
      be related to the expression of a novel protein kinase gene and not the
      prostanoid EP1 gene [Batshake, B., Sundelin, J., 1996. The mouse genes for the
      EP1 prostanoid receptor and the novel protein kinase overlap. Biochem. Biophys.
      Res. Commun. 227. 1329-1333].

PMID- 9537821
TI  - Pharmacological profile of antidepressants and related compounds at human
      monoamine transporters.
AB  - Using radioligand binding assays, we determined the equilibrium dissociation
      constants (KD's) for 37 antidepressants, three of their metabolites
      (desmethylcitalopram, desmethylsertraline, and norfluoxetine), some mood
      stabilizers, and assorted other compounds (some antiepileptics, Ca2+ channel
      antagonists, benzodiazepines, psychostimulants, antihistamines, and monoamines)
      for the human serotonin, norepinephrine, and dopamine transporters. Among the
      compounds that we tested, mazindol was the most potent at the human
      norepinephrine and dopamine transporters with KD's of 0.45 +/- 0.03 nM and 8.1 +/
      0.4 nM, respectively. Sertraline (KD = 25 +/- 2 nM) and nomifensine (56 +/- 3
      nM) were the two most potent antidepressants at the human dopamine transporter.
      We showed significant correlations for antidepressant affinities at binding to
      serotonin (R = 0.93), norepinephrine (R = 0.97), and dopamine (R = 0.87)
      transporters in comparison to their respective values for inhibiting uptake of
      monoamines into rat brain synaptosomes. These data are useful in predicting some
      possible adverse effects and drug-drug interactions of antidepressants and
      related compounds.

PMID- 9537822
TI  - Adenovirus-mediated expression of 5-HT1B receptors in cardiac ventricle myocytes;
      coupling to inwardly rectifying K+ channels.
AB  - The 5-HT1B receptor is expressed on nerve terminals where it inhibits
      neurotransmitter release. When expressed ectopically in fibroblasts, the 5-HT1B
      receptor inhibits adenylyl cyclase. However, in the central nervous system, the
      effect of this receptor on neurotransmitter release appears to be cAMP
      independent. We therefore investigated alternative effector systems that might be
      activated by the 5-HT1B receptor. We constructed a recombinant adenovirus that
      allows expression of high levels of the 5-HT1B receptor in a variety of cells. We
      chose cardiac ventricle myocytes because they express a muscarinic-gated,
      inwardly rectifying K+ channel (i[KACh]). In infected ventricle cells, both 5-HT
      and the muscarinic receptor agonist, carbachol, elicited a similar inwardly
      rectifying K+ current. The currents elicited by these agonists were pertussis
      toxin sensitive and were not additive. These results suggest a common signal
      transduction pathway for 5-HT1B and muscarinic receptors in ventricle cells.

PMID- 9537823
TI  - Modulation of alpha1B-adrenoceptor expression by agonist and protein kinase
      inhibitors.
AB  - The agonist-induced up-regulation of alpha1B-adrenoceptors in clone H99 of
      transfected Chinese hamster ovary cells that we reported previously (Zhu et al.,
      1996) was further investigated. Studies with a larger number of clones revealed
      that the up-regulation observed in H99 cells is atypical and that most other
      clones exhibit down-regulation under the same conditions. The role of protein
      kinases in the up-regulation of alpha1B-adrenoceptors in clone H99 was further
      investigated. Surprisingly, the protein kinase inhibitor staurosporine induced a
      similar up-regulation. Neither the selective protein kinase C inhibitor GF109203X
      nor the activator phorbol 12-myristate, 13-acetate altered receptor expression.
      The tyrosine kinase inhibitors genistein and its weaker analog daidzein did not
      induce up-regulation but blocked the up-regulation induced by epinephrine and by
      staurosporine. Up-regulation was blocked by the protein synthesis inhibitor
      cycloheximide. These studies suggest multiple mechanisms by which different
      protein kinases can modulate the expression of transfected alpha1B-adrenoceptors.

PMID- 9537824
TI  - Homologous and heterologous desensitisation of somatostatin-induced increases in
      intracellular Ca2+ and inositol 1,4,5-trisphosphate in CHO-K1 cells expressing
      human recombinant somatostatin sst5 receptors.
AB  - The mechanisms responsible for somatostatin (SRIF)-induced increases in
      intracellular Ca2+ concentration ([Ca2+]i) and subsequent desensitisation were
      studied in CHO-K1 cells expressing human sst5 receptors (CHOsst5 cells). To study
      the nature of the desensitisation, interactions with uridine triphosphate (UTP)
      were examined. SRIF (pEC50 7.10) and UTP (pEC50) 5.14) caused concentration
      dependent increases in [Ca2+]i but the SRIF maximum was about 40% of that to UTP.
      SRIF-, but not UTP-, induced increases in [Ca2+]i were transient and abolished by
      pertussis toxin. SRIF and UTP caused sustained increases in Ins(1,4,5)P3 but the
      SRIF maximum was about 30% of that to UTP. Removal of [Ca2+]e attenuated the SRIF
      induced peak rise in [Ca2+]i but had no effect on the peak increases in
      Ins(1,4,5)P3. UTP-induced increases in [Ca2+]i and Ins(1,4,5)P3 were attenuated
      in the absence of [Ca2+]e. Following pre-exposure to SRIF (1 microM) or UTP (100
      microM) for 5 min, subsequent SRIF responses were desensitised. Similar results
      were obtained in the absence of [Ca2+]e. Pre-exposure to SRIF had no effect on
      subsequent responses to UTP but in the absence of [Ca2+]e, responses to UTP were
      attenuated. The results suggest that SRIF but not UTP-induced increases in
      [Ca2+]i in CHOsst5 cells are mediated by pertussis toxin sensitive G proteins and
      are caused by an entry of extracellular Ca2+ and release from an Ins(1,4,5)P3
      sensitive Ca2+ store. Homologous or heterologous desensitisation of agonist
      induced increases in [Ca2+]i could be demonstrated in the presence or absence of
      extracellular Ca2+ respectively, and the latter appeared to involve depletion of
      a common intracellular Ca2+ store.

PMID- 9537825
TI  - Entacapone, a novel catechol-O-methyltransferase inhibitor for Parkinson's
      disease, does not impair mitochondrial energy production.
AB  - Entacapone, a novel mainly peripherally acting catechol-O-methyltransferase
      inhibitor used in the treatment of Parkinson's disease, was evaluated for its
      possible uncoupling activity in cell culture, in rat liver mitochondria, and in
      isolated guinea-pig heart. Entacapone did not stimulate respiration in the L1210
      murine T cell lymphoma cell line at the concentrations studied (5-40 microM).
      Furthermore, entacapone neither increased mitochondrial respiration nor impaired
      cardiac function at pharmacologically relevant concentrations (< 10 microM). In
      fact, the threshold concentration for increased mitochondrial oxygen consumption
      was 20 microM and half-maximal stimulation of respiration was not detected until
      58 microM. Surprisingly, tolcapone, another catechol-O-methyltransferase
      inhibitor, which acts both peripherally and centrally, stimulated respiration in
      L1210 cells at the lowest concentration studied (5 microM). In addition, 1 microM
      tolcapone increased mitochondrial respiration, indicating that it caused
      uncoupling at a much lower concentration than that of 2,4-dinitrophenol, a well
      known uncoupler of oxidative phosphorylation. Tolcapone also impaired the
      mechanical function and oxygen consumption of the isolated guinea-pig heart at 1
      microM. These results show that peripherally acting entacapone, unlike the brain
      penetrating tolcapone, is a safe catechol-O-methyltransferase inhibitor for the
      treatment of Parkinson's disease, since it does not interfere with mitochondrial
      energy metabolism at pharmacologically effective concentrations.

PMID- 9537826
TI  - CGP37157 modulates mitochondrial Ca2+ homeostasis in cultured rat dorsal root
      ganglion neurons.
AB  - The effects of 7-chloro-3,5-dihydro-5-phenyl-1H-4,1-benzothiazepine-2-on
      (CGP37157), an inhibitor of mitochondrial Na+/Ca2+ exchange, on depolarization
      induced intracellular free Ca2+ concentration ([Ca2+]i) transients were studied
      in cultured rat dorsal root ganglion neurons with indo-1-based microfluorimetry.
      A characteristic plateau in the recovery phase of the [Ca2+]i transient resulted
      from mitochondrion-mediated [Ca2+]i buffering. It was blocked by metabolic
      poisons and was not dependent on extracellular Ca2+. CGP37157 produced a
      concentration-dependent decrease in the amplitude of the mitochondrion-mediated
      plateau phase (IC50 = 4 +/- 1 microM). This decrease in [Ca2+]i was followed by
      an increase in [Ca2+]i upon removal of the drug, suggesting that Ca2+ trapped in
      the matrix was released when the CGP37157 was removed from the bath. CGP37157
      also inhibited depolarization-induced Ca2+ influx at the concentrations required
      to see effects on [Ca2+]i buffering. Thus, CGP37157 inhibits mitochondrial
      Na+/Ca2+ exchange and directly inhibits voltage-gated Ca2+ channels, suggesting
      caution in its use to study [Ca2+]i regulation in intact cells.

PMID- 9537827
TI  - Inhibition of N-,P/Q- and other types of Ca2+ channels in rat hippocampal nerve
      terminals by the adenosine A1 receptor.
AB  - The effects of the adenosine A1 receptor agonist, N6-cyclopentyladenosine (CPA),
      on both the increase in intracellular free Ca2+ concentration ([Ca2+]i) and on
      the release of endogenous glutamate in rat hippocampal synaptosomes were studied.
      The inhibitory effect of CPA on the increase in [Ca2+]i stimulated with 4
      aminopyridine was neutralized by the adenosine A1 receptor antagonist, 8
      cyclopentyl-1,3-dipropylxanthine (DPCPX). The inhibitory effect of CPA was
      greater in synaptosomes from the CA1 subregion than in whole hippocampal
      synaptosomes. The inhibitory effects of both CPA and of the Ca2+ channel
      blockers, omega-conotoxin GVIA, omega-conotoxin MVIIC or omega-conotoxin GVIA
      plus omega-conotoxin MVIIC, were greater than those caused by the Ca2+ channel
      blockers. The release of endogenous glutamate was inhibited by 41% by CPA. The
      inhibition observed when CPA and omega-conotoxin GVIA or CPA and omega-conotoxin
      MVIIC were present was also greater than the inhibition by the Ca2+ channel
      blockers alone. The presence of both omega-conotoxin GVIA and omega-conotoxin
      MVIIC did not completely inhibit the release of glutamate, and CPA significantly
      enhanced this inhibition. The membrane potential and the accumulation of
      [3H]tetraphenylphosphonium of polarized or depolarized synaptosomes was not
      affected by CPA, suggesting that adenosine did not increase potassium
      conductances. The present results suggest that, in hippocampal glutamatergic
      nerve terminals, adenosine A1 receptor activation partly inhibits P/Q- and other
      non-identified types of Ca2+ channels.

PMID- 9537828
TI  - Anorectic action of bombesin requires receptor for corticotropin-releasing factor
      but not for oxytocin.
AB  - The marked functional similarities between pharmacological effects of bombesin
      and of corticotropin-releasing factor (CRF), prompted the formulation and testing
      of our working hypothesis that BN may elicit its biological effects through the
      release of CRF. Central pretreatment with CRF receptor antagonists, alpha-helical
      CRF-(9-41) (alpha-CRF-(9-41)) or [D-Phe12, C(alpha)MeLeu37]CRF-(12-41)
      (CalphaMeCRF), blocked the effects of centrally administered bombesin on food
      intake and related behaviors and partially attenuated the satiety effects of
      systemically administered bombesin. We also attempted to characterize the
      specificity of this interaction through the combined use of bombesin with the
      oxytocin antagonist, [d(CH2)5, Tyr(OMe)2, Orn8]vasotocin (vasotocin). Central
      pretreatment with vasotocin failed to alter bombesin-induced behaviors,
      suggesting the absence of a pharmacological interaction between these two
      peptidergic systems. Finally, the CRF antagonist failed to reverse the oxytocin
      induced suppression of food intake, indicating that CRF does not have a direct
      role in the mediation and/or modulation of the effects of oxytocin on food
      intake. Thus, the present experiments support the contention that bombesin partly
      mediates its feeding-suppressant effects through interactions with CRF. The
      specificity of this interaction is supported by the lack of interaction between
      bombesin and/or CRF with oxytocin.

PMID- 9537829
TI  - [Projection of molecular epidemiology in medicine. Proceedings of an
      international symposium. April 17, 1996].

PMID- 9537830
TI  - Cleavage of membrane-associated ICAM-1 from astrocytes: involvement of a
      metalloprotease.
AB  - Disease of the central nervous system (CNS) with immune-mediated pathogenesis is
      frequently associated with enhanced expression of intercellular adhesion molecule
      1 (ICAM-1) on resident glial cells, including astrocytes. Recently, a soluble
      form of ICAM-1 (sICAM-1) has been demonstrated within the CNS and cerebrospinal
      fluid (CSF), arising from an intrathecal source. In this study, we investigated
      the ability of TNF-alpha treated astrocytes to generate sICAM-1 from a population
      of membrane-associated ICAM-1. To determine the ability of ICAM-1 to be released
      from the cell surface, generating sICAM-1, cell cultures were treated with TNF
      alpha for 21 h prior to cell surface protein iodination or biotinylation. We show
      that the membrane-associated form of ICAM-1 (approximately 90 KD) is converted to
      a soluble form (approximately 83 KD) in cell culture supernatants. The half-life
      of TNF-alpha induced membrane-associated ICAM-1 on rat astrocytes is
      approximately 5 h. The proteolytic cleavage process for the conversion of
      membrane-associated ICAM-1 to sICAM-1 was sensitive to Batimastat (BB94) and
      phosphoramidon, two inhibitors of metalloproteases, whereas inhibitors of serine
      , cysteine-, aspartic-, and chymotrypsin-like proteases had no effect on this
      process. These results indicate that astrocytes can be induced to produce sICAM
      1, and this process involves a metalloprotease that is induced/activated in a TNF
      alpha-dependent fashion. It is proposed that astrocytes may be a source of
      intrathecal sICAM-1 under inflammatory conditions.

PMID- 9537831
TI  - Effect of specific ion channel blockers on cultured Schwann cell proliferation.
AB  - Mitogenesis in a variety of tissues is known to be inhibited by K+ channel
      blockers such as tetraethylammonium (TEA) and 4-aminopyridine (4-AP). Using
      radiolabeled thymidine as a proliferation index we have examined what role, if
      any, specific K+ channels have in cultured Schwann cells that have been induced
      to proliferate by pre-exposure to mitogens. TEA and 4-AP are "broad-spectrum" in
      that they block a variety of different types of K+ channel. In contrast, we found
      that alpha-dendrotoxin (alpha-DTX), a specific blocker of the type 1 fast delayed
      rectifier current (the largest component of Schwann cell K+ current) does not
      affect proliferation, suggesting that type 1 current may not be involved in
      mitogenesis. This suggestion is supported by our finding that the values of the
      KD for the mitogenic effect (722 nM, 4-AP; 13 mM, TEA) are much larger than the
      corresponding electrophysiological values for type 1 channels (0.1 mM, 4-AP; 0.2
      mM, TEA). Charybdotoxin (200 nM) and iberiotoxin (100 nM), inhibitors of Ca2+
      activated K+ channels, cesium (5 mM), an inhibitor of inward rectifier channels,
      and furosemide (100 pM), which blocks Na+/K+/Cl- cotransport, all had no effect
      on proliferation. Interestingly, 4,4'-diisothiocyanatostilbene 2,2'-disulphonate
      (DIDS), which blocks voltage-gated Cl- channels, reduced proliferation. In
      summary, broad-spectrum K+ channel blockers inhibit Schwann cell proliferation,
      but inhibitors specific for type 1, Ca2+-activated, and inward rectifier K+
      channels do not. Whether the inhibition is mediated by type 2 K- channels, by an
      as yet unidentified Schwann cell K+ channel, or by another mechanism remains
      unclear.

PMID- 9537832
TI  - Regulation of oligodendrocyte differentiation: protein kinase C activation
      prevents differentiation of O2A progenitor cells toward oligodendrocytes.
AB  - Oligodendrocytes differentiate on a specific schedule in vivo in order to
      myelinate axons at the precise time and at the appropriate position. The current
      study was undertaken to obtain further insight as to how this timed appearance is
      regulated intracellularly. We observed that exposure of O2A progenitor cells in
      culture to phorbol 12-myristate 13-acetate (PMA; an activator of protein kinase
      C, PKC) inhibited their differentiation to oligodendrocytes by suppressing the
      expression of specific myelin markers at the O4-stage. To positively identify a
      role of PKC per se in differentiation, the use of a minimal medium with low serum
      content turned out to be essential. This was demonstrated by showing that the
      inhibitory effect of PMA on oligodendrocyte differentiation could be completely
      abolished by a combined action of insulin, triiodothyronine (T3), hydrocortisone
      and other components of a chemically defined medium (CDM). Furthermore, the PMA
      mediated inhibition of oligodendrocyte differentiation could be partially
      restored by activation of the cAMP signal transduction pathway. The results
      indicate that PKC plays a crucial role in the differentiation of O2A progenitor
      cells toward oligodendrocytes: PKC activation prevents differentiation of O2A
      progenitor cells, whereas differentiation toward oligodendrocytes is dependent on
      other signaling compounds which may counteract the PKC signal transduction route.

PMID- 9537833
TI  - Role of astrocyte-derived tissue-type plasminogen activator in the regulation of
      endotoxin-stimulated nitric oxide production by microglial cells.
AB  - In mixed glial cell cultures from cerebral cortices of newborn rats, endotoxin
      induces nitric oxide (NO) production in microglial cells. Earlier we demonstrated
      that endotoxin induced NO production by microglial cells is inhibited in the
      presence of astroglial cells by transforming growth factor beta (TGFbeta). Both
      microglial and astroglial cells produce TGFbeta in a biologically inactive form,
      which can be activated by plasmin generated by plasminogen activators (PA). In
      the present paper we describe studies on the mechanism by which glial cells may
      activate inactive TGFbeta and its potential inhibitory effect on NO production by
      microglial cells. Inhibition of plasmin increased NO production in endotoxin
      treated mixed glial cell cultures. Subsequently, antibodies against tissue-type
      plasminogen activator (tPA) increased NO production in endotoxin-treated mixed
      glial cell cultures while amiloride, an inhibitor for urokinase (uPA), had no
      effect. We hereby concluded that tPA is the crucial PA involved in plasmin
      production resulting in inhibition of NO production in mixed glial cell cultures.
      Zymography and Northern blot analysis of purified astroglial, microglial, and
      mixed glial cell cultures demonstrated that astroglial cells produce tPA and a
      plasminogen activator inhibitor (PAI-1) and are thereby responsible for the
      production of plasmin which may activate the inactive TGF in these cultures. In
      conclusion, astroglial-derived tPA plays a major role in the inhibition of NO
      production by endotoxin-treated microglial cells through enhanced plasmin
      production and possible subsequent TGFbeta activation.

PMID- 9537834
TI  - In vitro and in vivo induction of heme oxygenase-1 in rat glial cells: possible
      involvement of nitric oxide production from inducible nitric oxide synthase.
AB  - To determine whether heme oxygenase-1 (HO-1) protein is induced by endogenous
      nitric oxide (NO) in rat glial cultures, we examined the effects of
      lipopolysaccharide (LPS), interferon-gamma (IFN-gamma), and NO donors such as S
      nitroso-N-acetylpenicillamine (SNAP), in mixed glial cells and in vivo rat
      hippocampus. In cultured glial cells, treatment with LPS induced the expression
      of 130-kd inducible NO synthase (iNOS) after 6 h, and NO2- accumulation and
      enhancement of the protein level of 33-kd HO-1 after 12 h. In addition, treatment
      with SNAP induced HO-1 expression after 6 h. Although NOS inhibitors such as NG
      nitro-L-arginine (NNA) and NG-methyl-L-arginine did not change LPS-induced iNOS
      expression, these inhibitors suppressed both NO2- accumulation and the
      enhancement of HO-1. Immunocytochemistry showed that treatment with LPS for 24 h
      induced iNOS immunoreactivity predominantly in ameboid microglia, while this
      treatment induced HO-1-immunoreactivity in both microglia and astrocytes. In in
      vivo rat hippocampus, microinjection of LPS plus IFN-gamma, or SNAP after 24 h
      also induced HO-1 immunoreactivity in reactive microglia and astrocytes. In
      addition, intraperitoneal administration of NNA inhibited HO-1 immunoreactivity
      induced by the microinjection of LPS plus IFN-gamma. These results suggest that
      endogenous NO production by iNOS in microglia causes autocrine and paracrine
      induction of HO-1 protein in microglia and astrocytes in vitro and in rat brain.

PMID- 9537835
TI  - 4-hydroxynonenal, a lipid peroxidation product, impairs glutamate transport in
      cortical astrocytes.
AB  - Astrocytes possess plasma membrane glutamate transporters that rapidly remove
      glutamate from the extracellular milieu and thereby prevent excitotoxic injury to
      neurons. Cellular oxidative stress is increased in neural tissues in a variety of
      acute and chronic neurodegenerative conditions. Recent findings suggest that
      oxidative stress increases neuronal vulnerability to excitotoxicity and that
      membrane lipid peroxidation plays a key role in this process. We now report that
      4-hydroxynonenal (HNE), an aldehydic product of membrane lipid peroxidation,
      impairs glutamate transport in cultured cortical astrocytes. Impairment of
      glutamate transport occurred within 1-3 h of exposure to HNE; FeSO4, an inducer
      of membrane lipid peroxidation, also impaired glutamate transport. Vitamin E
      prevented impairment of glutamate transport induced by FeSO4, but not that
      induced by HNE, consistent with HNE acting as an effector of lipid peroxidation
      induced impairment of glutamate transport. Glutathione, which binds and thereby
      detoxifies HNE, prevented HNE from impairing glutamate transport. Western blot,
      immunoprecipitation, and immunocytochemical analyses using an antibody against
      HNE-protein conjugates provided evidence that HNE covalently binds to many
      different astrocytic proteins including the glutamate transporter GLT-1. Data
      further suggest that HNE promotes intermolecular cross-linking of GLT-1 monomers
      to form dimers. HNE also induced mitochondrial dysfunction and accumulation of
      peroxides in astrocytes. Impairment of glutamate transport and mitochondrial
      function occurred with sublethal concentrations of HNE, concentrations known to
      be generated in cells exposed to various oxidative insults. Collectively, our
      data suggest that HNE may be an important mediator of oxidative stress-induced
      impairment of astrocytic glutamate transport and may thereby play a role in
      promoting neuronal excitotoxicity.

PMID- 9537836
TI  - Response of the oligodendrocyte progenitor cell population (defined by NG2
      labelling) to demyelination of the adult spinal cord.
AB  - Elucidation of the response of oligodendrocyte progenitor cell populations to
      demyelination in the adult central nervous system (CNS) is critical to
      understanding why remyelination fails in multiple sclerosis. Using the anti-NG2
      monoclonal antibody to identify oligodendrocyte progenitor cells, we have
      documented their response to antibody-induced demyelination in the dorsal column
      of the adult rat spinal cord. The number of NG2+ cells in the vicinity of
      demyelinated lesions increased by 72% over the course of 3 days following the
      onset of demyelination. This increase in NG2+ cell numbers did not reflect a
      nonspecific staining of reactive cells, as GFAP, OX-42, and Rip antibodies did
      not co-localise with NG2 + cells in double immunostained tissue sections. NG2 +
      cells incorporated BrdU 48-72 h following the onset of demyelination. After the
      onset of remyelination (10-14 days), the number of NG2+ cells decreased to 46% of
      control levels and remained consistently low for 2 months. When spinal cords were
      exposed to 40 Grays of x-irradiation prior to demyelination, the number of NG2+
      cells decreased to 48% of control levels by 3 days following the onset of
      demyelination and remained unchanged at 3 weeks. Since 40 Grays of x-irradiation
      kills dividing cells, these studies illustrate a responsive and nonresponsive
      NG2+ cell population following demyelination in the adult spinal cord and suggest
      that the responsive NG2+ cell population does not renew itself.

PMID- 9537837
TI  - Transforming growth factor-beta inhibition of cytokine-induced vascular cell
      adhesion molecule-1 expression in human astrocytes.
AB  - Leukocyte transmigration across the blood-brain barrier (BBB) is a cardinal
      feature of central nervous system (CNS) inflammation. Astrocytes form an integral
      part, both structurally and functionally, of the BBB. Vascular cell adhesion
      molecule-1 (VCAM-1), a member of the immunoglobulin gene superfamily, is involved
      in extravasation into inflamed tissues and activation of T-lymphocytes. In this
      study, we investigated the role of TGF-beta, an immunosuppressive cytokine, in
      regulating cytokine-induced VCAM-1 expression in astrocytes. Human astroglioma
      cell lines and primary human fetal astrocytes were examined for VCAM-1 gene
      expression after treatment with proinflammatory cytokines (TNF-alpha, IL-1beta,
      IFN-gamma) in the absence or presence of TGF-beta. Astroglioma cell lines as well
      as primary human fetal astrocytes expressed low levels of VCAM-1 constitutively,
      and the proinflammatory cytokines induced marked increases in VCAM-1 expression,
      particularly TNF-alpha and IL-1beta. The inclusion of TGF-beta1 or TGF-beta2 with
      the proinflammatory cytokines inhibited VCAM-1 gene expression to varying degrees
      (33-93%) in all the astroglioma cell lines and primary fetal cells. These results
      indicate that TGF-beta is an important regulator of cytokine induced VCAM-1
      expression on astrocytes and may prove useful clinically in controlling CNS
      inflammation.

PMID- 9537838
TI  - Vitamin E induces ramification and downregulation of adhesion molecules in
      cultured microglial cells.
AB  - Microglial cells in the healthy adult CNS possess a characteristic ramified
      morphology and show little or no expression of major histocompatibility complex
      (MHC) or adhesion molecules. In contrast, microglial cells isolated from newborn
      rat brains inevitably show a nonramified amoeboid morphology and express
      immunoeffector molecules, such as MHC class I and II, and various adhesion
      molecules thought to be markers of microglial activation. Furthermore, they
      produce large amounts of oxygen radicals. Treatment of cultured microglial cells
      with the antioxidants vitamin E (alpha-tocopherol) and vitamin C (ascorbic acid)
      induced a ramified microglial morphology after 48 h in vitro, otherwise only seen
      in healthy adult CNS tissue or in co-culture with astrocytes. Morphological
      transformation of microglial cells was quantified by morphometric analysis and
      was found to be statistically significant. Ramification of microglia induced by
      vitamin E was accompanied by downregulated expression of adhesion molecules
      leukocyte function antigen-1, very late antigen-4, and intercellular adhesion
      molecule-1, as assessed by FACS analysis and immunocytochemistry. Moreover, cell
      numbers of microglia treated with vitamin E remained stable within 7 days in
      vitro, whereas untreated controls showed a cell loss of 81.5%. These data show
      that vitamin E acts as a protective compound in dissociated microglial cell
      cultures. In conclusion, our results suggest that vitamin E and vitamin C shift
      microglial morphology toward ramification and induce an immunological
      deactivation. These changes seem to be mediated by oxidative mechanisms.

PMID- 9537839
TI  - Endogenous opioid system in developing normal and jimpy oligodendrocytes: mu and
      kappa opioid receptors mediate differential mitogenic and growth responses.
AB  - The early development of both neurons and neuroglia may be modulated by signaling
      through opioid mediated pathways. Neurons and astroglia not only express specific
      types of opiate receptors, but also respond functionally to opioids with altered
      rates of proliferation and growth. The present study was undertaken to determine
      if opioids also modulate development of the other major CNS macroglial cell, the
      oligodendrocyte (OL). Using well-characterized polyclonal antibodies specific for
      delta-, kappa-, and mu-opiate receptors, OLs grown in vitro were shown to express
      mu-receptors at a very immature stage prior to expression of kappa-receptors.
      This developmentally regulated sequence differs from the pattern of expression in
      neurons and astroglia. delta-receptors are apparently absent from cultured OLs.
      OLs also have physiologic responses to selective mu- and kappa-receptor agonists
      and antagonists. Exposure of relatively immature O4+ OLs to the mu-receptor
      agonist PL017 [H-Tyr-Pro-Phe(N-Me)-D-Pro-NH2] resulted in a significant
      enhancement in the rate of DNA synthesis. This effect, which was not observed in
      more mature MBP+ OLs, was entirely blocked by the antagonist naloxone. Although
      the kappa-receptor pathway appeared to be uninvolved in controlling
      proliferation, the kappa-receptor antagonist nor-binaltorphimine significantly
      increased the size of myelin-like membranes produced by the cultured OLs.
      Interestingly, OLs derived from the jimpy mouse, a mutant characterized by an
      almost complete lack of CNS myelin and premature death of OLs, were found to be
      deficient in kappa-opiate receptors. Our findings clearly show that OLs not only
      express specific opiate receptors, but also respond to changes in their level of
      stimulation in ways that could profoundly impact nervous system morphology and
      function. If opiate receptors are expressed by OLs in vivo, their pharmacological
      manipulation might provide a novel pathway for modulating OL and myelin
      production both during development and in demyelinated conditions.

PMID- 9537841
TI  - ICOP-X. 10th International Congress of Protozoology. Sydney, Australia, 21-25
      July 1997.

PMID- 9537840
TI  - Regulation of astrocyte GFAP expression by TGF-beta1 and FGF-2.
AB  - Astrocytes play a critical role in the development of the CNS and its response to
      injury and disease. A key indicator of astrocyte activation is the increased
      accumulation of intermediate filaments composed of glial fibrillary acidic
      protein (GFAP). Treatment of astrocytes in vitro with transforming growth factor
      beta1 (TGF-beta1) produced little morphological change, but resulted in a
      significant increase in GFAP mRNA and protein. Treatment with basic fibroblast
      growth factor (FGF-2) produced a dramatic change from a polygonal to a stellate
      morphology, and resulted in a significant decrease in GFAP mRNA and protein. FGF
      2 also inhibited the TGF-beta1-mediated increase in GFAP mRNA and protein.
      Cycloheximide did not block the effects of TGF-beta1 or FGF-2 on GFAP mRNA
      levels, but blocked the inhibitory effects of FGF-2 on the TGF-beta1-mediated
      increase in GFAP expression. All effects of FGF-2 were blocked by co-incubation
      with 5'-methylthioadenosine, a specific inhibitor of FGF-2-induced tyrosine
      kinase activity and FGF receptor (FGFR) autophosphorylation. We also examined
      astrocyte expression of FGFR, and demonstrate the presence of FGFR 1 and 2, and
      lower levels of FGFR 3. Our results demonstrate that TGF-beta1 and FGF-2 cause
      differential effects on the astrocyte cytoskeleton and morphology, suggesting an
      uncoupling of process outgrowth from GFAP synthesis.

PMID- 9537843
TI  - Regarding, Ting, IJROBP 38(5):1105-1111.

PMID- 9537842
TI  - Detecting linkage disequilibrium between a polymorphic marker locus and a trait
      locus in natural populations.
AB  - A novel statistical model was developed to test for linkage disequilibrium
      between a polymorphic genetic marker locus and a locus underlying a quantitative
      trait (QTL) in natural populations using principles of analysis of variance of
      unbalanced data and analysis of regression involving data of non-normal
      distribution. Powers of these statistical tests are formulated as functions of
      census population size, allelic frequencies at the marker locus and the trait
      locus, additive and dominance effects at the QTL as well as the coefficient of
      linkage disequilibrium. Theoretical predictions of the power are validated by
      extensive Monte Carlo simulations. Among all these factors examined, the amount
      of the disequilibrium and the size of effect of the QTL are of most importance in
      determining the power, and the dominance and the allele frequencies at the two
      loci have substantial effects on the power. Numerical analyses based upon the
      theoretical calculations and simulation studies favour use of regression of the
      number of marker alleles on the trait phenotypes as a measure of detection of
      linkage disequilibrium. Theoretical analysis is also performed to investigate
      robustness of the formula for predicting the variance of the regression
      coefficient, which requires normality of the regression variables, whereas
      normality may not be strictly warranted.

PMID- 9537844
TI  - Proceedings of the International Session at the 61st Annual Scientific Meeting of
      the Japanese Circulation Society "Circulation 97". Tokyo, Japan, March 31-April
      2, 1997.

PMID- 9537845
TI  - Response to November Letters to the Editor.

PMID- 9537846
TI  - Association between HLA class II alleles and protection from or susceptibility to
      chronic hepatitis C.
AB  - BACKGROUND/AIMS: Recent studies have suggested that the course of chronic
      hepatitis C may be influenced by the immunogenetic background of the host.
      Specifically, HLA-DR11 (5) has been associated with less advanced hepatitis C
      virus (HCV)-related liver disease. The aim of the present study was to
      investigate whether HLA-DRB1*11 subtypes or HLA-DQA1 and DQB1 genes might be
      associated with protection from or susceptibility to chronic HCV infection,
      histological severity of HCV-induced liver disease and infecting HCV genotype.
      METHODS: Ninety-nine unrelated outpatients with histologically documented chronic
      hepatitis C were studied and their allele frequencies were compared with those of
      179 ethnically matched controls and with those of 41 HCV RNA-positive patients
      with persistently normal aminotransferase levels (HCV carriers). HLA-DQ types and
      HLA-DRB1*11 subtypes were determined by polymerase chain reaction gene
      amplification with sequence specific primers. RESULTS: None of 10 DQA1 or 12 DQB1
      alleles was significantly associated with susceptibility to or protection from
      chronic HCV infection or with histological staging or with HCV genotype. However,
      analysis of DQA1-DQB1 combinations showed that DQA1*0201-DQB1*0201 combination
      was significantly more frequent in patients compared to controls, both in cis
      (26.3% vs 16.2%, p = 0.04, odds ratio = 1.8, 95% confidence interval, 0.96-3.5)
      and in trans (12.1% vs. 1.1%, p = 0.0001, OR = 12.2, 95% CI, 2.6-113.7). HCV
      carriers did not differ from controls or from patients in the frequency of DQA1
      DQB1 combinations. The extended haplotype DRB1*1104, DQA1*0501, DQB1*0301 was
      seen significantly less frequently in patients than in controls (8% vs 22.3%, p =
      0.0025, OR = 0.31, 95% CI, 0.12-0.7) or HCV-RNA carriers (8% vs 26.8%, p = 0.003,
      OR = 0.24, 95% CI, 0.08-0.73). CONCLUSIONS: Immunogenetic factors may play a role
      in determining both protection from and susceptibility to chronic hepatitis C,
      the trans-dimer DQA1*0201-DQB1*0201 predisposing to and the DRB1*1104, DQA1*0501,
      DQB1*0301 haplotype protecting from chronic hepatitis C.

PMID- 9537847
TI  - Analysis of the treatment effect on recurrent bleeding and death in patients with
      cirrhosis and esophageal varices: multistage competing-risks model compared to
      conventional methods. The Copenhagen Esophageal Varices Sclerotherapy Project.
AB  - BACKGROUND/AIMS: Multiple recurrences of bleeding with high mortality in
      cirrhosis with esophageal varices have been inadequately analyzed in previous
      trials. We propose analysis by the multistage competing-risks model, specifying
      the effect on overall mortality as an effect on mortality during bleeding, rate
      of cessation of bleeding, mortality rate without bleeding, and rate of
      rebleeding. METHODS: The Copenhagen Esophageal Varices Project enrolled patients
      after first bleeding and randomized 94 to usual treatment and 93 to sclerotherapy
      as supplement. During 9-52 months of follow-up, rebleeding occurred in 49 and 42,
      and death in 68 and 60 patients, respectively. The proportional hazards
      regression model (Cox model) was used for reanalysis both by the multistage
      competing-risks model and by conventional analysis for overall mortality and rate
      of first rebleeding. In the multistage model, time zero was at entry to any new
      disease stage, of which the first four were analyzed - two bleeding stages and
      two bleeding-free stages. RESULTS: The conventional analysis showed a reduction
      of overall mortality rate in the sclerotherapy group of borderline significance,
      but no effect on rate of rebleeding. The multistage model indicated that
      sclerotherapy reduced the rate of rebleeding late in the disease course, and
      particularly after the first rebleeding. Rate of cessation of bleeding and
      mortality rates during bleeding and without bleeding were not affected by
      sclerotherapy. CONCLUSIONS: Conventional analysis may give misleading
      conclusions, which might be avoided by applying the multistage model. The effect
      of sclerotherapy on overall mortality may be ascribed entirely to the reduced
      rate of rebleeding.

PMID- 9537848
TI  - Nutritional and prognostic significance of serum hypothyroxinemia in hospitalized
      patients with liver cirrhosis.
AB  - BACKGROUND/AIMS: A variety of severe illnesses can induce changes in thyroid
      hormone metabolism, leading to findings referred to as "sick euthyroid syndrome".
      In several groups of patients the reduction of serum thyroxine concentration
      (T4), characteristic of the low-T4 variant of sick euthyroid syndrome, has been
      found to be a good predictor of survival. Although the pathophysiology of
      hormonal alterations has not yet been defined, nutritional deficits have been
      suggested to play a role. The study aimed to define the prognostic and
      nutritional significance of serum thyroxine in liver cirrhosis. METHODS: Thyroid
      hormones and nutritional status were evaluated in a group of 75 consecutive
      hospitalized patients with cirrhosis, followed-up clinically for 12 months.
      RESULTS: A low-T4 variant of sick euthyroid syndrome was found in 23 of the 75
      enrolled patients with cirrhosis (30.6%). Serum T4, but not serum T3, correlated
      with mid-arm muscle circumference (p < 0.01), an indicator of muscle protein
      compartment. While both serum T3 and T4 correlated directly with serum proteins
      and inversely with Child-Pugh score, only T4 was predictive of outcome. Patients
      with the low-T4 variant of sick euthyroid syndrome showed significantly lower
      short- and long-term survival rates compared to those with normal serum T4
      concentrations (p < 0.008 at 3 months, p < 0.001 at 6 months and 1 year). A
      multivariate analysis using the proportional hazards Cox's regression procedure
      showed that serum T4, but not serum T3 or nutritional parameters, improves the
      prognostic capacity of Child-Pugh score (p < 0.01). CONCLUSIONS: These data
      indicate that the low T4-variant of sick euthyroid syndrome distinguishes a
      subgroup of patients with cirrhosis at risk for decreased survival. The inclusion
      of T4 in the Child-Pugh score, by improving its prognostic power, may optimize
      the selection of patients with advanced cirrhosis to receive specific therapy
      such as transplantation.

PMID- 9537849
TI  - Osteopenia in rats with liver cirrhosis: beneficial effects of IGF-I treatment.
AB  - BACKGROUND/AIMS: Liver cirrhosis is associated with osteopenia and also with low
      levels of IGF-I. This hormone has been reported to stimulate bone formation in
      states of undernutrition and low bone turnover. Our aims were to evaluate whether
      osteopenia develops in male Wistar rats with CCl4-induced cirrhosis and whether
      IGF-I is effective in the restoration of bone mass in these animals. METHODS:
      Cirrhotic rats were distributed into two groups: group CI (n = 12) which received
      placebo and group CI + IGF (n = 12) which was treated with human recombinant IGF
      I (2 microg/100 g bw/day, s.c., 21 days). Twelve normal animals which received
      placebo constituted the control group. On the 22nd day, the animals were
      sacrificed, and bone parameters were analyzed in femur and/or tibia. RESULTS:
      Posterior-anterior and latero-medial diameters were similar in all groups. Also,
      no significant differences were observed in bone contents of calcium, total
      proteins, collagen and hydroxyapatite in CI rats as compared with controls.
      However, CI rats showed significant reductions in bone weight (-13.5%, p <
      0.001), total bone density (-9.28%, p < 0.001), and increased perimedullar bone
      resorption and urinary levels of deoxypyridinoline (a marker of bone resorption).
      In CI + IGF rats these parameters improved significantly as compared with CI
      animals. CONCLUSIONS: Osteopenia characterized by loss of bone mass and preserved
      bone composition is found in rats with CCl4-induced cirrhosis. This bone disorder
      is partially corrected by treatment with low doses of IGF-I. Since osteoporosis
      seems to be the predominant form of osteopenia in patients with cirrhosis, IGF-I
      should be considered as a possible therapy for this disorder.

PMID- 9537850
TI  - Hepatitis B virus precore mutants in serum and liver of Southern African Blacks
      with hepatocellular carcinoma.
AB  - BACKGROUND/AIM: The aim of this study was to sequence the precore region of HBV
      isolated from serum and tumorous and non-tumorous liver tissue from patients with
      hepatocellular carcinoma to identify mutations that might play a role in
      malignant transformation. METHODS: HBV DNA was extracted from 62 sera, 14
      tumorous and 12 non-tumorous liver tissue samples of patients with hepatocellular
      carcinoma, amplified by the polymerase chain reaction and sequenced directly.
      RESULTS: Thirty-nine patients were HBeAg-negative and 23 HBeAg-positive. Missense
      mutations were present predominantly in HBeAg-negative sera. The most common
      missense mutation, a guanine to thymine transversion, occurred at nucleotide 1862
      in the bulge of the encapsidation signal; it was more prevalent in HBeAg-negative
      (10/39) than in HBeAg-positive patients (1/23) (p = 0.03). Mutations known to
      prevent HBeAg synthesis were detected in seven sera; five with an 1896 stop-codon
      mutation, one with an 1817 nonsense mutation, and one with a frameshift mutation
      caused by an insertion between 1838 and 1839. Missense mutations and deletions
      were present more often in tumorous tissue derived from HBsAg-negative patients.
      In the tumours missense mutations occurred at position 1862 and 1899, and the
      deletions affected direct repeat 1 and/or the encapsidation signal and included
      the x gene stop-codon. CONCLUSIONS: The 1862 mutation, and other missense
      mutations and deletions detected in the precore gene, may disrupt HBV DNA
      replication and/or signal peptide cleavage leading to HBeAg-negativity.
      Disruption of viral replication may promote integration of unencapsidated
      replicative intermediates and hence contribute to hepatocarcinogenesis.

PMID- 9537851
TI  - Progression of hepatocellular carcinoma as reflected by nuclear DNA ploidy and
      cellular differentiation.
AB  - BACKGROUND/AIMS: Intratumor heterogeneity of DNA ploidy within a single
      hepatocellular carcinoma is not well understood. The present study was designed
      to examine the histologic distribution of intratumor DNA ploidy in hepatocellular
      carcinomas of different growth types in relation to cell differentiation.
      METHODS: Twenty patients (16 men and four women; mean age, 60.2 years) with
      hepatocellular carcinoma (mean diameter, 4.3 cm) were studied. One hundred and
      twenty-seven samples from different sites of each tumor were analyzed by
      determination of the nuclear DNA content and histological examination. RESULTS:
      The DNA ploidy was heterogeneous in nine (45%) of the 20 tumors. Five tumors had
      a mixture of diploid and aneuploid regions, and the remaining four consisted of
      aneuploid regions with different DNA indices. There was no significant difference
      in patient characteristics between the heterogeneous and homogeneous groups. A
      significant correlation was found between tumor growth type and the incidence of
      heterogeneity. Only 16% of single nodular carcinomas without intratumor septal
      formation exhibited heterogeneity, while single nodular tumors with septal
      formation or confluent multinodular tumors were associated with high incidences
      of different DNA ploidy patterns or DNA indices. There was no aneuploidy in well
      differentiated foci, while aneuploidy was frequently found in moderately or
      poorly differentiated foci (incidences of 67% and 74%, respectively).
      CONCLUSIONS: Heterogeneity of DNA ploidy may develop along with changes in growth
      pattern and cell dedifferentiation or by confluence of nodules originating from
      different tumor cell clones.

PMID- 9537852
TI  - Steroid withdrawal is safe and beneficial in stable cyclosporine-treated liver
      transplant patients.
AB  - BACKGROUND: In the immunosuppression of orthotopic liver transplant recipients,
      steroids are used despite their unspecific action and long-term side effects. Few
      studies have been carried out on steroid withdrawal and many aspects remain to be
      elucidated. METHODS: A prospective study was performed to analyse the effect of
      steroid withdrawal on 86 patients with stable graft function, more than 1 year
      after orthotopic liver transplant. Thirty patients had chronic hepatitis in the
      graft. Seventy-two continued with cyclosporine (CsA) and 14 with CsA-azathioprine
      (AZA) therapy. The follow-up was 23.2 +/- 8.1 months (range 12-52 months). A
      paired t-test was used for statistical analysis. RESULTS: No acute or chronic
      rejection occurred, and steroids were not reinstituted. There were no changes in
      serum transaminase levels, but bilirubin levels decreased (p < 0.01). At the end
      of the follow-up, we found improvements in blood pressure in hypertensive
      patients (systolic 156.1 +/- 8.4 mmHg vs. 139.4 +/- 8.7 mmHg, p < 0.001); body
      weight (72 +/- 13.5 kg vs. 70.8 +/- 13 kg, p < 0.05); serum cholesterol (211.3 +/
      42 mg/dl vs. 191.6 +/- 43.5 mg/dl, p < 0.001) and bone mineral density in lumbar
      spine (0.823 +/- 0.13 g/cm2 vs. 0.893 +/- 0.135 g/cm2, p < 0.001). Four of ten
      diabetic patients were no longer insulin-dependent and insulin requirements
      decreased in the remaining six. No significant biochemical changes were found in
      patients with hepatitis in the graft, and we found an improvement in inflammatory
      activity in the nine biopsied patients. CONCLUSIONS: Steroid withdrawal with CsA
      monotherapy is feasible, safe and beneficial in patients who have stable liver
      graft function 1 year after orthotopic liver transplant. We consider that AZA
      therapy is not necessary unless drastic reduction of CsA levels is required
      because of renal dysfunction.

PMID- 9537853
TI  - Detection of endothelin-1 and its receptors in rat liver endothelial cells by in
      situ reverse transcriptase-polymerase chain reaction.
AB  - BACKGROUND/AIMS: Endothelin (ET)-1 is a potent vasoconstrictor, also in the
      liver; it increases intrahepatic resistance by targeting hepatic stellate cells
      acting via the ET-A receptor. The role of the expression and regulation of ET-1
      and its receptors in endothelial liver cells, an important site of ET production
      in normal liver, is not yet well documented. In the present study, we have
      developed an in situ reverse transcriptase (RT)-polymerase chain reaction method
      to elucidate the presence of prepro-ET-1, ET-A and ET-B receptors in isolated rat
      liver endothelial cells. METHODS: After in situ collagenase-pronase liver
      perfusion, endothelial cells were isolated using a Nycodenz gradient. RT
      polymerase chain reaction and in situ RT-polymerase chain reaction were performed
      using specific primers for prepro-endothelin, ET-A and ET-B. RESULTS: Trypan blue
      exclusion test showed a viability of more than 90% in the freshly isolated non
      parenchymal cells. RT-polymerase chain reaction showed expression of prepro
      endothelin, ET-A and ET-B in RNA isolated from the endothelial cells. After in
      situ RT-polymerase chain reaction, we detected cytoplasmatic staining
      representing the presence of mRNA in the endothelial cells, with all sets of
      primers. About 60-80% of cells were positive. Negative controls, in which the RT
      step was omitted, did not show any cytoplasmatic staining. CONCLUSIONS:
      Endothelin 1 and both ET-A and ET-B receptors are expressed in rat endothelial
      liver cells. The expression of ET and its receptors in liver endothelial cells
      could be important in the development of liver diseases and the regulation of
      microvascular exchange.

PMID- 9537854
TI  - Hyde's prurigo nodularis and chronic HCV hepatitis.
AB  - The authors describe a woman with chronic active hepatitis, Hyde's prurigo
      nodularis and hepatitis C virus infection. The association of these three
      pathologies and their parallel evolution during treatment suggest a possible
      pathogenic link between the chronic hepatitis C virus infection and the skin
      disease.

PMID- 9537855
TI  - Chronic hepatitis induced by Jin Bu Huan.
AB  - BACKGROUND/AIMS: Jin Bu Huan and other Chinese herbal products are widely taken
      remedies. They have been developed as a natural alternative to traditional drugs
      in the treatment of various ailments. Their ability to induce several side
      effects such as acute hepatitis has already been described. We report a case of
      chronic hepatic damage following administration of Jin Bu Huan Anodyne tablets.
      METHODS: The patient, a 49-year-old man, developed biochemical signs of liver
      damage 2 months after beginning Jin Bu Huan intake (3 tablets/daily) including
      biopsy-proven chronic hepatitis with moderate fibrosis. Virological, autoimmune,
      metabolic or other hepatotoxic causes were excluded. Liver function impairment
      was resolved by discontinuing Jin Bu Huan intake. CONCLUSIONS: This case
      reinforces the already known hepatotoxicity of this product and should make us
      think more about the uncontrolled use of alternative products.

PMID- 9537856
TI  - Images in hepatology. Extrahepatic portal vein aneurysm.

PMID- 9537857
TI  - Lamivudine resistance in chronic hepatitis B.

PMID- 9537858
TI  - Persistence of gp210 and multiple nuclear dots antibodies does not correlate with
      recurrence of primary biliary cirrhosis 6 years after liver transplantation.

PMID- 9537859
TI  - In vitro reactivity of cryoglobulin IgM and IgG in hepatitis C virus-associated
      mixed cryoglobulinemia.
AB  - BACKGROUND/AIMS: Mixed cryoglobulinemia is frequently associated with chronic
      hepatitis C virus infection. We aimed to clarify the mechanism, kinetics and
      participating proteins in cryoprecipitate formation, which are still being
      debated. METHODS: Eighteen patients with cryoglobulinemia were studied. Isolated
      serum cryoprecipitates and purified cryoglobulin IgM and IgG fractions were
      analyzed in vitro by turbidimetry for temperature-dependent complex formation.
      Immunoglobulin reactivity, i.e. in cryoprecipitates and in cryoglobulin-free
      sera, was studied using immunoblot and enzyme immunoassays. HCV RNA was detected
      by reverse transcriptase/polymerase chain reaction. RESULTS: By turbidimetry,
      purified cryo-IgM precipitated (in the absence of HCV RNA) with cryo-IgG as well
      as with non-cryoglobulin IgG and with IgG Fc or F(ab')2 fragments. In contrast,
      purified cryo-IgG did not precipitate with non-cryoglobulin IgM. Anti-HCV IgG
      reactivity was found in cryoglobulin-free sera, in cryoprecipitates and in
      purified cryoglobulin IgG fractions. The respective titers were similar. Purified
      cryo-IgM did not react to HCV-encoded proteins. Binding of cryo-IgM to
      heterologous IgG was inhibited by intact IgG (up to a mean of about 52%) as well
      as by IgG Fc (33%) and F(ab')2 fragments (17%). Binding of cryo-IgM to IgG was
      enhanced at low temperature (4 degrees C vs. 37 degrees C), particularly for type
      III cryoglobulin IgM. CONCLUSIONS: In hepatitis C virus-associated
      cryoglobulinemia the in vitro precipitate formation depended on cryo-IgM, while
      IgG appeared to act as an unspecific antigenic partner. Hepatitis C viral
      particles were probably not required. Cryo-IgM binding occurred primarily to
      intact IgG. Anti-HCV reactivity of either cryo-IgM or cryo-IgG was not necessary
      for precipitate formation. Regarding the pathogenesis, a direct hepatitis C virus
      protein-dependent stimulation of B-cells producing cryo-IgM seems to be unlikely.

PMID- 9537860
TI  - Characteristics of patients with dual infection by hepatitis B and C viruses.
AB  - BACKGROUND/AIMS: The purpose of this study was to compare the epidemiological,
      biochemical, virological and histological characteristics of patients with
      chronic hepatitis B and C with those of patients suffering from chronic hepatitis
      C alone. METHODS: Twenty-three patients with chronic hepatitis C, who were anti
      HCV positive and HBs antigen positive, were studied and subdivided into two
      groups according to the presence or absence of HBV DNA replication. They were
      compared to 69 age- and sex-matched patients with chronic hepatitis who were anti
      HCV positive and HBs antigen negative. All patients were HCV RNA positive by PCR,
      anti-HIV negative and anti-HDV negative. HBV DNA and HCV RNA were detected in
      serum by means of a branched DNA assay and PCR. The HCV serotypes were determined
      by the Chiron Riba HCV serotyping SIA technique. The histological characteristics
      included the Knodell score. RESULTS: Epidemiological, biochemical and virological
      parameters were not different between the two groups. Only the prevalence of
      cirrhosis was greater in chronic hepatitis B and C patients than in patients with
      chronic hepatitis C alone (p = 0.01). Among chronic hepatitis B and C patients,
      HCV RNA level was significantly lower in HBV DNA positive than in HBV DNA
      negative patients (p = 0.01). Indeed, histological lesions were more severe in
      HBV DNA positive than in HBV DNA negative patients, including prevalence of
      cirrhosis (p = 0.01), Knodell score (p = 0.05) and, among the latter, piecemeal
      necrosis (p = 0.01) and fibrosis (p = 0.05). The characteristics of patients with
      dual infection did not differ according to the mode of contamination and duration
      of HBV disease, except for a shorter duration in patients contaminated by drug
      abuse than in other patients. CONCLUSIONS: These results suggest that HBV DNA
      replication inhibits HCV RNA replication in patients with chronic active
      hepatitis B and C but increases the severity of histological lesions.

PMID- 9537861
TI  - HCV and HGV in B-cell non-Hodgkin's lymphoma.
AB  - BACKGROUND/AIMS: A causative role of hepatitis C virus infection (HCV) has been
      discussed in the pathogenesis of mixed cryoglobulinaemia and in B-cell non
      Hodgkin's lymphoma. No data are available concerning the newly discovered
      hepatitis G virus (HGV) and extrahepatic manifestations such as haematological
      malignancies. But, HCV and HGV most probably belong to the same family of
      Flavivirus. Consequently, we looked for the prevalence of HCV, HGV and
      cryoglobulins in patients with B-cell non-Hodgkin's lymphoma. METHODS: Serum
      samples from 69 patients with non-Hodgkin's lymphoma were studied. Diagnosis of
      non-Hodgkin's lymphoma was established according to the Kiel classification.
      Active HCV- and HGV infections were investigated using polymerase chain reaction
      for detection of viral RNA. Cryoglobulins were detected from serum and monoclonal
      immunoglobulin components were analysed with immunofixation electrophoresis. In
      addition, we assessed the clinical course of HCV- and HGV-infected patients under
      chemotherapy. RESULTS: Three of 69 (4.3%) patients with B-cell non-Hodgkin's
      lymphoma were HCV-infected and nine non-Hodgkin's lymphoma patients (13.0%) were
      positive for hepatitis G virus RNA. All HGV infected patients were suffering from
      low-grade non-Hodgkin's lymphoma. No HGV-infected patient was co-infected by HCV
      and neither HCV- nor HGV-infected patients showed clinical signs of chronic liver
      disease before, during or after chemotherapy. Serum samples from all patients
      were devoid of cryoglobulins. CONCLUSIONS: HCV seems to have no significance for
      the pathogenesis of non-Hodgkin's lymphoma in Germany. The increased prevalence
      of hepatitis G (16.3%) in patients with low-grade non-Hodgkin's lymphoma could
      suggest a pathological consequence of HGV infection outside of the liver.
      Evidence of clinically relevant hepatic disease in HGV infected patients was not
      obtained. Further, chemotherapy does not seem to affect the subsequent clinical
      course of HGV infection.

PMID- 9537862
TI  - Human hepatic stellate cells express class I alcohol dehydrogenase and aldehyde
      dehydrogenase but not cytochrome P4502E1.
AB  - BACKGROUND/AIMS: Alcohol dehydrogenase, cytochrome P4502E1 (CYP2E1), and aldehyde
      dehydrogenase are known to play an important role in alcohol metabolism in the
      liver. Although the ethanol oxidation pathways are mainly localized in
      hepatocytes, we examine whether human hepatic stellate cells might also
      metabolize ethanol and acetaldehyde. METHODS: Hepatic stellate cells were
      isolated from normal human livers and exposed in vitro to 50 mmol/l ethanol or 85
      micromol/l acetaldehyde for different periods of time. Alcohol
      dehydrogenase/aldehyde dehydrogenase activity and CYP2E1 protein expression were
      measured in hepatic stellate cells. Moreover, alcohol dehydrogenase and aldehyde
      dehydrogenase mRNA expression were evaluated in hepatic stellate cells. RESULTS:
      Exposure of hepatic stellate cells to ethanol for 24 h resulted in a 5-fold
      increase in cell alcohol dehydrogenase activity. The effect of ethanol on alcohol
      dehydrogenase activity was paralleled by a significant increase in the alcohol
      dehydrogenase mRNA expression in hepatic stellate cells. Acetaldehyde
      significantly increased the activity of high affinity aldehyde dehydrogenase in
      hepatic stellate cells, whereas ethanol was devoid of any effect. Acetaldehyde
      also induced high affinity aldehyde dehydrogenase mRNA expression in hepatic
      stellate cells. CYP2E1 was not expressed in hepatic stellate cells either in
      basal condition or after ethanol/acetaldehyde exposure. CONCLUSIONS: This study
      shows that human hepatic stellate cells have the capacity to metabolize both
      ethanol and acetaldehyde through a class I alcohol dehydrogenase- and an aldehyde
      dehydrogenase-oxidizing pathway. Conversely, no detectable levels of CYP2E1
      associated proteins are expressed in these cells.

PMID- 9537863
TI  - Ethanol-induced changes of intracellular thiol compartmentation and protein redox
      status in the rat liver: effect of tauroursodeoxycholate.
AB  - BACKGROUND/AIMS: Ethanol impairs cellular antioxidant defense and protein
      metabolism. Hydrophilic bile acids are protective against ethanol-induced
      cytotoxicity. This study investigated the compartmentation of intracellular thiol
      and protein redox status after acute ethanol intoxication in the liver and the
      effect of tauroursodeoxycholate pretreatment. METHODS: The concentrations of
      total glutathione, glutathione bound to proteins, sulfhydryl proteins, carbonyl
      proteins and malondialdehyde were measured in hepatic cytosol, mitochondria and
      nuclei after oral administration of 25% ethanol (4 g/kg) or isocaloric
      carbohydrate solution to rats. The metabolisms of ethanol and acetaldehyde were
      investigated by giving 4-methylpyrazole (1 mmol/kg i.p.) or cyanamide (15 mg/kg
      i.p.) 1 h prior to ethanol ingestion. One group of rats received
      tauroursodeoxycholate (12 mg/kg p.os) 1 h before ethanol ingestion. RESULTS:
      Ethanol significantly decreased the glutathione concentrations. Significant
      increases in glutathione bound to proteins, carbonyl protein and malondialdehyde
      concentrations were also noted, especially at the mitochondrial level. Enhanced
      carbonyl protein formation was also observed (p < 0.01). The inhibition of
      acetaldehyde metabolism, but not ethanol metabolism, exaggerated the alterations
      produced by ethanol. Pretreatment with tauroursodeoxycholate significantly
      reduced lipid and protein oxidation, particularly in mitochondria. By contrast,
      no changes were observed in glutathione content and compartmentation.
      CONCLUSIONS: Ethanol intoxication differentially impairs thiol and protein redox
      status in the subcellular fractions of rat liver. These alterations seem
      dependent on acetaldehyde rather than ethanol. Tauroursodeoxycholate
      administration protects proteins and lipids from ethanol-induced oxidative damage
      without influencing the glutathione content and compartmentation.

PMID- 9537865
TI  - Effects of the nitric oxide synthase inhibitors N(G)-nitro-L-arginine methyl
      ester and aminoethyl-isothiourea on the liver microcirculation in rat
      endotoxemia.
AB  - BACKGROUND/METHODS: The question whether nitric oxide protects or impairs organ
      perfusion during early endotoxemia has not been completely answered. To evaluate
      the regulative function of nitric oxide on organ microvascular perfusion and
      leukocyte accumulation during endotoxemia, we studied the influence of a non
      selective nitric oxide inhibitor and a preferential inducible nitric oxide
      synthase inhibitor (respectively, N(G)-nitro-L-arginine methyl ester and
      aminoethyl-isothiourea) on liver microcirculation (intravital fluorescence
      microscopy) in a rat model. RESULTS: Two hours after intraportal injection of
      lipopolysaccharide (5 mg/kg in 10 min) the rats were randomly treated and
      received a bolus dose of N(G)-nitro-L-arginine methyl ester (10 mg/kg, n = 7),
      aminoethyl-isothiourea (10 mg/kg, n = 6) or normal saline, (n = 7). After 1 h,
      N(G)-nitro-L-arginine methyl ester blockade yielded a higher rate of non-perfused
      sinusoids than normal saline (27 +/- 2% vs 19 +/- 5%, p < 0.05). LPS-induced
      leukocyte stagnation in sinusoids was further increased (p < 0.05) in all groups
      after 1 h treatment, but N(G)-nitro-L-arginine methyl ester clearly accentuated
      leukocyte accumulation in sinusoids as compared to normal saline (69 +/- 19% vs
      16 +/- 4%, p < 0.05). Both modalities of nitric oxide blockade elicited a
      significant enhancement in the number of leukocytes adherent to the
      postsinusoidal venules in contrast to normal saline (N(G)-nitro-L-arginine methyl
      ester 48 +/- 17%, aminoethyl-isothiourea 33 +/- 9% vs normal saline 1 +/- 5%, p <
      0.05). CONCLUSIONS: We conclude that complete nitric oxide blockade aggravates
      lipopolysaccharide-induced hepatic microvascular perfusion failure and enhances
      leukocyte accumulation, in both sinusoids and post-sinusoidal venules. The
      preferential inducible nitric oxide synthase inhibitor aminoethyl-isothiourea has
      a moderate negative effect, favoring leukocyte adhesion in postsinusoidal
      venules, and its usefulness demands further research, especially concerning its
      late effects.

PMID- 9537864
TI  - Metadoxine accelerates fatty liver recovery in alcoholic patients: results of a
      randomized double-blind, placebo-control trial. Spanish Group for the Study of
      Alcoholic Fatty Liver.
AB  - BACKGROUND/AIMS: Our aim was to investigate the effectiveness of metadoxine
      (pyridoxol L, 2 pyrrolidone-5-carboxylate) in the treatment of alcoholic fatty
      liver. METHODS: A double-blind randomized multicenter trial involving 136 chronic
      active alcoholic patients diagnosed with fatty liver by clinical, biochemical and
      ultrasonographic criteria was performed. Patients were treated with 1500 mg/day
      of metadoxine (n = 69) or placebo (n = 67) for 3 months. Patients were clinically
      and biochemically evaluated every month. Ultrasonography was performed before and
      after treatment. RESULTS: At the end of the study there was a significant
      improvement in the liver function tests in both groups. However, the changes were
      more rapid and greater in patients treated with metadoxine, in whom significant
      changes in serum levels of bilirubin, aminotransferases and gammaglutamyl
      transpeptidase were already observed after 1 month of treatment, and
      normalization of these parameters was observed at the end. After treatment, the
      percentage of patients with ultrasonographic signs of steatosis was significantly
      lower in the metadoxine group (28% vs 70%, p < 0.01) and the degree of steatosis
      was also lower in this group. Sixteen patients treated with metadoxine and 15
      with placebo continued drinking. Alcohol intake was lower than initially, and
      similar in both groups. In the metadoxine group, the biochemical changes were
      similar in both the abstinent and the nonabstinent patients. In contrast, in the
      placebo group the improvement in the liver function tests was significantly
      higher in abstinents. Among patients who continued drinking, the prevalence (45%
      vs 92%, p < 0.05) and the degree of steatosis were also significantly lower in
      patients treated with metadoxine. CONCLUSIONS: In patients with alcoholic fatty
      liver, metadoxine accelerates the normalization of liver function tests and the
      ultrasonographic changes, even in those who do not completely abstain from
      alcohol intake. Thus, metadoxine could be useful in the treatment of the early
      stages of alcoholic liver disease.

PMID- 9537866
TI  - Limited T cell receptor Vbeta-chain repertoire of liver-infiltrating T cells in
      autoimmune hepatitis.
AB  - BACKGROUND/AIMS: To characterize the cellular immune reactions in autoimmune
      hepatitis, the T cell receptor repertoire of liver-infiltrating and circulating T
      cells was studied. METHODS: Nucleic acids of liver-tissue and peripheral blood
      derived T cells from 12 patients with untreated autoimmune hepatitis, four
      patients with chronic hepatitis C and three patients with toxic liver injury were
      extracted and analysed using a semiquantitative RT-PCR with a panel of T cell
      receptor Vbeta family specific primers. After agarose gel electrophoresis, the
      distribution of T cell receptor (TCR) Vbeta molecules was assessed by
      densitometry. Furthermore, results were compared to the TCR Vbeta distribution of
      10 healthy blood donors. RESULTS: Four of 12 patients with untreated autoimmune
      hepatitis but no patients with chronic hepatitis C and toxic liver injury showed
      a significant overexpression of TCR Vbeta3 (17.8% +/- 2.6% vs. 9.3% +/- 4.6%; p =
      0.01) and three an overexpression of Vbeta13.1 (14.6% +/- 2.3% vs. 6.6% +/- 3.5%;
      p = 0.02) molecules compared to the TCR Vbeta-distribution in healthy blood
      donors. In addition, Vbeta3+ T cells were found enriched in the liver tissue
      compared to autologous peripheral blood in three autoimmune hepatitis patients
      (15.3% +/- 7.0% vs. 5.2% +/- 3.1%; L/B ratio: 2.9), while Vbeta13.1+ T cells were
      enriched in the liver tissue from one of three patients with overexpression.
      CONCLUSIONS: In autoimmune hepatitis a disease specific compartmentalisation of
      TCR Vbeta3+ T cells was observed in the liver tissues. Although their specificity
      was unknown, this might indicate that these infiltrating T cells could have
      relevance for abnormal immunoregulation.

PMID- 9537867
TI  - Is severe cryptogenic chronic hepatitis similar to autoimmune hepatitis?
AB  - BACKGROUND/AIMS: It has been reported that severe cryptogenic chronic hepatitis
      may be a subgroup of autoimmune hepatitis. The aims of this study were to
      investigate the clinical features, liver function tests, human leukocyte antigens
      and response to immunosuppressive therapy in severe cryptogenic chronic
      hepatitis, and to compare the findings in such patients with those in patients
      with autoimmune hepatitis. METHODS: History of alcohol and hepatotoxic drug
      intake, markers of metabolic liver disease, autoantibodies (antinuclear antibody,
      smooth muscle antibody, antibody to liver/kidney microsome type 1), and viral
      markers (HBsAg, HBV DNA, anti-HCV, HCV RNA) were negative in all severe
      cryptogenic chronic hepatitis patients (histological activity index > 9 and
      alanine aminotransferase level > 2 x normal). Fifteen cryptogenic patients (13
      women; mean age, 33 +/- 16 years) and seven autoimmune patients (seven women;
      mean age, 28 +/- 3.9 years; five type 1; two type 2a) received prednisolone and
      azathioprine for at least 2 years. RESULTS: Cryptogenic chronic hepatitis
      patients were similar to patients with autoimmune hepatitis with respect to age,
      sex, clinical presentation, liver function tests and Knodell scores at admission.
      HLA phenotype frequencies were comparable between cryptogenic and autoimmune
      groups: BW6 (77% vs. 100%), DR4 (62% vs. 57%), and HLA B8 (15% vs. 43%). The
      rates of complete and partial remissions achieved during therapy were 87% vs. 57%
      and 13% vs. 29%, respectively (p > 0.05). CONCLUSIONS: The clinical, biochemical
      and HLA phenotypic features, and the responsiveness to immunosuppressive therapy
      in severe cryptogenic chronic hepatitis support the idea that it may be an
      autoimmune liver disease similar to autoimmune hepatitis.

PMID- 9537868
TI  - HBV-specific lymphoproliferative and cytokine responses in patients with chronic
      hepatitis B.
AB  - BACKGROUND/AIMS: Hepatitis B virus specific T cell responses are crucial for
      viral elimination but their nature is not fully understood. METHODS: We studied
      the regulation of proliferation and cytokine production after antigenic
      stimulation in peripheral blood mononuclear cells from chronically HBV-infected
      patients and subjects with natural immunity after recovery from an acute
      infection. Proliferation and production of interferon-gamma, IL-10 and tumor
      necrosis factor-alpha were determined after stimulation with HBcAg, HBeAg or
      HBsAg in the absence or presence of IL-12 or neutralizing antibodies to IL-12,
      interferon-gamma, IL-4, IL-10 or tumor necrosis factor-alpha. RESULTS: Upon
      stimulation with HBcAg or HBeAg, peripheral blood mononuclear cells from chronic
      hepatitis B virus patients displayed a clear class-II restricted proliferative
      response (SI greater than 2.5). Both interferon-gamma (less than 50 IU/ml) and IL
      10 levels up to 600 pg/ml were detected. Proliferative or cytokine responses to
      HBsAg were very weak or absent. Addition of IL-12 to HBeAg-stimulated cultures
      increased the production of interferon-gamma to more than 200 IU/ml in all
      patients and slightly increased the production of IL-10. Neutralization of IL-10
      increased the HBeAg-induced interferon-gamma production but had no effect on
      tumor necrosis factor-alpha production. Addition of anti-IL-4 or anti-tumor
      necrosis factor-alpha had no significant influence on proliferation or cytokine
      release. Importantly, in both chronic hepatitis B virus patients and naturally
      immune subjects, IL-12 induced proliferative and interferon-gamma responses in
      peripheral blood mononuclear cells stimulated with HBsAg. CONCLUSIONS: Our data
      indicate that peripheral blood mononuclear cells from chronic hepatitis B virus
      patients proliferate and produce interferon-gamma and IL-10 upon HBeAg but not
      upon HBsAg stimulation. IL-12 augments the HBeAg-induced responses and,
      additionally, provokes proliferation and interferon-gamma production in HBsAg
      stimulated cultures.

PMID- 9537869
TI  - Resident human hepatic lymphocytes are phenotypically different from circulating
      lymphocytes.
AB  - BACKGROUND/AIMS: Murine and human studies have documented the existence of
      subpopulations of lymphocytes in particular tissues that differ phenotypically
      and functionally from those in peripheral blood and may mature locally. Since
      little is known about lymphocyte subpopulations in the normal human liver, we
      have analysed the surface phenotypes of lymphocytes isolated from liver specimens
      taken from 15 donors at the time of liver transplantation, and compared these
      with those of peripheral blood lymphocytes. METHODS: Hepatic lymphocytes were
      prepared by mechanical dissociation and enzymatic digestion of liver tissue. The
      cells were stained with a panel of monoclonal antibodies (CD3, CD4, CD8, CD19,
      CD56, gammadeltaTCR, alphabetaTCR, CD8alpha-chain, CD8alphabeta dimer), and
      analysed by flow cytometry. In situ characterisation of hepatic lymphocytes was
      by haematoxylin and eosin staining of fixed liver sections and by
      immunohistochemical staining for common leukocyte antigen and CD3. RESULTS:
      Significant numbers of hepatic T lymphocytes were localised to the portal tracts
      and parenchyma of normal liver specimens. Flow cytometry revealed that the
      CD4/CD8 ratio (1:3.5) was consistently reversed compared with that in peripheral
      blood (2:1). Other lymphocyte populations identified include double positive
      CD3+CD4+CD8+ cells which accounted for a mean of 5.5% (range 3-11.6%) of hepatic
      CD3+ cells compared with 1.3% in blood (range 0.7-3.6%; p < 0.007), and double
      negative CD3+ CD4-8- cells (14.5%; range 2.7-29% compared with 5.0%; range 2.1
      10.8%, p < 0.02). Over 15% (range 6.8-34%) of all hepatic CD3+ cells expressed a
      gammadeltaTCR compared to 2.7% (range 0.9-4.7%) of CD3+ peripheral blood
      lymphocytes (p < 0.004) and almost 50% of these coexpressed CD8. The CD8 alpha
      chain was expressed without the beta-chain (CD8alpha+beta-) by 15.4% (range 4
      29.1%) of hepatic T cells, but this phenotype was undetectable among peripheral
      blood lymphocytes (p < 0.009). Cells expressing both the T cell marker CD3 and
      the natural killer cell marker CD56 constituted 31.6% (range 14-54%) of all
      hepatic CD3+ lymphocytes but were rarely present amongst peripheral blood
      lymphocytes (0-6%; p < 0.0001). CONCLUSIONS: These data are the first to describe
      and quantify unconventional T lymphocyte subpopulations in the normal adult human
      liver which may have specialised functions in regional immune responses and which
      may differentiate locally. These findings have important implications for our
      understanding of hepatic immunoregulation and the pathogenic mechanisms involved
      in viral and immune-mediated liver disease and allograft rejection.

PMID- 9537870
TI  - Correction of maternal serum bile acid profile during ursodeoxycholic acid
      therapy in cholestasis of pregnancy.
AB  - BACKGROUND/AIMS: Intrahepatic cholestasis of pregnancy is characterized by
      pruritus and increased levels of serum bile acids, and is often associated with
      premature delivery, fetal distress, and perinatal mortality. The aims of the
      present study were: (i) to better define the serum bile acid profile in
      intrahepatic cholestasis of pregnancy and its potential usefulness for
      differential diagnosis; (ii) to investigate the effect of ursodeoxycholic acid
      treatment on the bile acid pool; and (iii) to investigate possible adverse
      effects of therapy. METHODS: Fifteen patients with intrahepatic cholestasis of
      pregnancy were enrolled in this study. Ursodeoxycholic acid (14 mg/kg body weight
      per day) was administered for 13 +/- 5 days. Twenty normal pregnant women served
      as controls. Serum bile acid profile was analyzed by high-performance liquid
      chromatography. RESULTS: Patients with cholestasis of pregnancy showed
      significant alterations in the proportion of primary bile acids, with an increase
      in cholic acid (64.0 +/- 3.0% vs. 32.2 +/- 1.8%, p < 0.01), and a decrease in
      chenodeoxycholic acid (20.8 +/- 1.4% vs. 31.9 +/- 1.3%, p < 0.01), as compared to
      controls, resulting in a marked elevation in the cholic/chenodeoxycholic acid
      ratio (3.4 +/- 0.5 vs. 1.1 +/- 0.1, p < 0.01). The glycine/taurine ratio was
      reduced in cholestasis of pregnancy (0.8 +/- 0.1 vs. 1.4 +/- 0.1, p < 0.01).
      During ursodeoxycholic acid administration its proportion in serum increased from
      1.4 +/- 0.6% (0.6 +/- 0.2 micromol/l) at baseline to 24.7 +/- 2.3% (5.9 +/- 1.9
      micromol/l) with therapy (p < 0.01). This increment was accompanied by a
      significant decrease in the percentage of cholic acid (28.2 +/- 2.6%, p < 0.01)
      and an elevation in chenodeoxycholic acid proportion (25.0 +/- 1.9%, N.S.).
      Although lithocholic acid concentration in serum was maintained with treatment
      (1.2 +/- 0.2 micromol/l vs. 1.7 +/- 0.5 micromol/l), there was a significant
      increase in lithocholic acid proportion (p < 0.01) from 3.3 +/- 0.5% at baseline
      to 7.4 +/- 1.3% during therapy. The glycine/taurine ratio of serum bile acid pool
      returned to normal after ursodeoxycholic acid administration (1.7 +/- 0.3).
      CONCLUSIONS: These results establish the importance of ursodeoxycholic acid
      treatment for the correction of maternal serum bile acid profile in cholestasis
      of pregnancy, indicating that ursodeoxycholic acid may improve fetal prognosis.

PMID- 9537872
TI  - 7th Biennial meeting of the Leeds Castle Polyposis Group (LCPG) and the 9th
      annual meeting of the International Collaborative Group on Hereditary Non
      Polyposis Colorectal Cancer (ICG-HNPCC). Noordwijk, the Netherlands, 4-7 June
      1997. Abstracts.

PMID- 9537871
TI  - Effect of tauroursodeoxycholic acid on bile-acid-induced apoptosis and cytolysis
      in rat hepatocytes.
AB  - BACKGROUND/AIMS: In cholestatic liver disease, bile acids may initiate or
      aggravate hepatocellular damage. Cellular necrosis and cell death may be due to
      detergent effects of bile acids, but apoptosis may also play a role. In
      cholestasis, the conditions determining either apoptotic or cytolytic cell death
      are still unclear. Primary rat hepatocytes in culture represent a suitable model
      to study bile-acid-induced liver damage. METHODS: Glycochenodeoxycholic acid, a
      hydrophobic bile acid, was used to induce cell damage. Tauroursodeoxycholic acid,
      a hydrophilic bile acid, served as substrate to study possible protective effects
      of such compounds. To study the time and concentration dependency of bile-acid
      induced cytolysis and apoptosis, morphologic alterations, hepatocellular enzyme
      release and nucleosomal DNA fragmentation were evaluated. RESULTS: Bile-acid
      induced cytolysis, as indicated by hepatocellular enzyme release and by
      morphologic signs of membrane destruction, increased with concentration and time.
      Addition of tauroursodeoxycholic acid to the incubation medium reduced cytolysis
      significantly, indicating a direct hepatoprotective effect of this bile acid
      against the detergent action of hydrophobic bile acids. In contrast to cytolysis,
      apoptosis with DNA fragmentation was induced by low concentrations of
      glycochenodeoxycholic acid a few hours after incubation. Coincubation with
      tauroursodeoxycholic acid in equimolar concentrations significantly reduced
      apoptosis, indicating another direct hepatoprotective effect of
      tauroursodeoxycholic acid. CONCLUSIONS: It seems likely that in severe
      cholestasis, bile-acid-induced injury of hepatocytes is due mainly to cytolysis,
      whereas in moderately severe cholestasis apoptosis represents the predominant
      mechanism of bile acid toxicity. Tauroursodeoxycholic acid may reduce both bile
      acid-induced apoptosis and cytolysis.

PMID- 9537873
TI  - Feeling someway.

PMID- 9537874
TI  - [Changes in the body fluid and fluid therapy in acute fulminant pancreatitis].

PMID- 9537875
TI  - Geographic choroiditis and retinal vasculitis in rheumatoid arthritis.
AB  - A 37-year-old man developed geographic choroiditis and retinal vasculitis in the
      left eye while taking 3.5 mg/day oral prednisolone for rheumatoid arthritis. The
      choroidal lesions stopped growing when the dose of prednisolone was increased to
      60 mg/day, while its tapering resulted in the recurrence and enlargement of the
      choroidal lesions to the macula. The patient experienced further recurrence twice
      in the following year. Indocyanine green angiography demonstrated the obstruction
      of choroidal arteries in addition to the complete obstruction of the
      choriocapillaris in a fresh lesion. This case was the first to have geographic
      choroiditis on the background of a systemic inflammatory disease.

PMID- 9537876
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 11-1998. A 35-year-old woman with obstructive pulmonary disease
      and cystic changes on CT scans of the chest.

PMID- 9537877
TI  - Building-related illnesses.

PMID- 9537878
TI  - Building-related illnesses.

PMID- 9537879
TI  - Effect of inhaled formoterol and budesonide on exacerbations of asthma.

PMID- 9537880
TI  - Effect of inhaled formoterol and budesonide on exacerbations of asthma.

PMID- 9537881
TI  - The interleukin-4 receptor variant Q576R in hyper-IgE syndrome.

PMID- 9537882
TI  - Improvement in CD4+ cell counts despite persistently detectable HIV load.

PMID- 9537883
TI  - Performance of two rapid tests for Plasmodium falciparum malaria in patients with
      rheumatoid factors.

PMID- 9537884
TI  - Privacy and medical-records research.

PMID- 9537885
TI  - Privacy and medical-records research.

PMID- 9537886
TI  - Privacy and medical-records research.

PMID- 9537887
TI  - Privacy and medical-records research.

PMID- 9537888
TI  - Organophosphorus poisoning in the Kashmir Valley, 1994 to 1997.

PMID- 9537889
TI  - [In memoriam Istvan Kadar (1926-1997)].

PMID- 9537890
TI  - Vestibular dysfunction : lessons and legacies from space. Proceedings of a
      symposium. Washington, D.C., USA. September 28, 1996.

PMID- 9537892
TI  - Papers from a National Academy of Sciences Colloquium on Protecting Our Food
      Supply: The Value of Plant Genome Initiatives. Irvine, California, USA. June 2-5,
      1997.

PMID- 9537891
TI  - [Proceedings of the 2nd Seminar on Pediatric Nephrology. Verona, 30 May 1997].

PMID- 9537893
TI  - The anonymous letter.

PMID- 9537894
TI  - Lyme disease and the passenger pigeon?

PMID- 9537895
TI  - Free calcium signals.

PMID- 9537896
TI  - Bacteriophage collagen.

PMID- 9537897
TI  - The oldest human.

PMID- 9537898
TI  - Ames tackles the riddle of life.

PMID- 9537899
TI  - Cancer warriors claim a victory.

PMID- 9537900
TI  - Toxicologists shed new light on old poisons.

PMID- 9537901
TI  - The bare bones of catalysis.

PMID- 9537903
TI  - Getting an inside look at cells' chemistry.

PMID- 9537902
TI  - Exploring how to get at--and eradicate--hidden HIV.

PMID- 9537904
TI  - Progress in progressive hearing loss.

PMID- 9537905
TI  - Promoter logic.

PMID- 9537906
TI  - Ultrafast magnetic resonance imaging. A new window on brain research.

PMID- 9537907
TI  - CPU by DNA?

PMID- 9537908
TI  - Pinpoint assays.

PMID- 9537910
TI  - A third technological revolution.

PMID- 9537909
TI  - Yeast sites on the net.

PMID- 9537911
TI  - Senate panel backs large NIH increase.

PMID- 9537912
TI  - First Alzheimer's diagnosis confirmed.

PMID- 9537913
TI  - No-new-neurons dogma loses ground.

PMID- 9537914
TI  - Receptor links blood vessels, axons.

PMID- 9537915
TI  - Double helix doubles as engineer.

PMID- 9537916
TI  - Weighing DNA for fast genetic diagnosis.

PMID- 9537917
TI  - Expansion of the allelic exclusion principle?

PMID- 9537918
TI  - [Epoetin alfa: recent strategies of use].

PMID- 9537919
TI  - [Perspectives of breast cancer from the ECCO-9 and from the 15th National
      Convention of Experimental and Clinical Oncology].

PMID- 9537920
TI  - [Directives from the commander of the Main Military Medical Administration of the
      Ministry of Defense of the Russian Federation].

PMID- 9537921
TI  - [Issue dedicated to the 70th anniversary of the birth of V.Z. Gorkin. Various
      biomedical aspects of amino oxidases and their inhibitors].

PMID- 9537922
TI  - [An analysis of the complications from the surgical treatment of hydrocephalus of
      different etiologies].
AB  - Complications after CSF shunting procedures in 83 (278 in all) patients with
      hydrocephalus of various origin were analyzed. Complications were more frequently
      observed in patients with tumor pathology.

PMID- 9537923
TI  - ASHG statement. Professional disclosure of familial genetic information. The
      American Society of Human Genetics Social Issues Subcommittee on Familial
      Disclosure.

PMID- 9537924
TI  - Mitochondrial DNA and ancient population growth.
AB  - In recent years, the study of mitochondrial DNA (mtDNA) variation has entered a
      new phase with an increasing emphasis on interpretations of demographic, rather
      than phylogenetic, history. Human mtDNA variation fits a "sudden expansion"
      model, where the human species expanded rapidly in size during the Late
      Pleistocene. This paper examines the sudden expansion model with the goal of
      partitioning total mtDNA diversity in contemporary populations into two
      components--diversity that existed prior to the population expansion and
      diversity that arose after the expansion. A method is developed for estimating
      these components. Analysis of mtDNA diversity within selected human populations
      shows that 64-80% of mtDNA diversity in contemporary populations arose after the
      expansion, a consequence of a high mutation rate relative to the number of
      generations since expansion. The basic model is extended to two components of
      excess diversity in sub-Saharan Africa--differences in population size before the
      expansion and differences in the timing of expansion. Results suggest that excess
      sub-Saharan African mtDNA diversity is due to the combined effects of the sub
      Saharan African population being larger in size prior to the expansion and
      expanding earlier.

PMID- 9537925
TI  - Superior exercise performance in lifelong Tibetan residents of 4,400 m compared
      with Tibetan residents of 3,658 m.
AB  - Few environments challenge human populations more than high altitude, since the
      accompanying low oxygen pressures (hypoxia) are pervasive and impervious to
      cultural modification. Work capacity is an important factor in a population's
      ability to thrive in such an environment. The performance of work or exercise is
      a measure of the integrated functioning of the O2 transport system, with maximal
      O2 uptake (.VO2max) a convenient index of that function. Hypoxia limits the
      ability to transport oxygen: maximal O2 uptake decreases with ascent to high
      altitude, and years of high altitude residence do not restore sea level .VO2max
      values. Since Tibetans live and work at some of the highest altitudes in the
      world, their ability to exercise at very high altitude (>4,000 m) may define the
      limits of human adaptation to hypoxia. We transported 20 Tibetan lifelong
      residents of > or =4,400 m down to 3,658 m in order to compare them with 16
      previously studied Tibetan residents of Lhasa (3,658 m). The two groups of
      Tibetans were matched for age, weight, and height. All studies were performed in
      Lhasa within 3 days of the 4,400 m Tibetans' arrival. Standard test protocol and
      criteria were used for attaining .VO2max on a Monark bicycle ergometer, while
      measuring oxygen uptake (.VO2, ml/kg - min STPD), heart rate (bpm), minute
      ventilation (VE, 1/min BTPS), and arterial oxygen saturation (SaO2, %). The 4,400
      m compared with 3,658 m residents had, at maximal effort, similar .VO2 (48.5 +/-
      1.2 vs. 51.2 +/- 1.4 ml/kg - min, P = NS), higher workload attained (211 +/- 6
      vs. 177 +/- 7 watts, P < 0.01), lower heart rate(176 +/- 2 vs. 191 +/- 2 bpm, P <
      0.01), lower ventilation (127 +/- 5 vs. 149 +/- 5 l/min BTPS, P < 0.01), and
      similar SaO2(81.9 +/- 1.0 vs. 83.7 +/- 1.2%, P = NS). Furthermore, over the range
      of submaximal workloads, 4,400 m compared with 3,658 m Tibetans had lower .VO2 (P
      < 0.01), lower heart rates (P < 0.01), and lower ventilation (P < 0.01) and SaO2
      (P < 0.05). We conclude that Tibetans living at 4,400 m compared with those
      residing at 3,658 m achieve greater work performance for a given .VO2 at
      submaximal and maximal workloads with less cardiorespiratory effort.

PMID- 9537926
TI  - On the quantification of suckling intensity in primates.
AB  - The inhibitory effect that suckling has on the reproductive function of primate
      mothers varies as a function of the intensity with which they are suckled. Here
      we present an easily computed index of one parameter of suckling intensity,
      namely the temporal patterning of suckling bouts. High intensity suckling is
      characterized by frequent nursing bouts demarcated by short interbout intervals.
      Therefore, our suckling index is based on the brevity of observed interbout
      intervals, more specifically the proportion of such intervals that fail to exceed
      a criterion length. The index is an appropriate means of making interspecific
      comparisons of the development of infant suckling and is well suited for
      application to field data that include interbout intervals that were not observed
      in their entirety. To demonstrate its utility, we apply the index to field data
      collected on the suckling behavior of free-ranging rhesus monkey (Macaca mulatta)
      infants in India. In this context, we demonstrate that, in rhesus, between-infant
      differences in suckling intensity manifest themselves early in the postpartum
      period and contribute to between-female differences in the timing of first mating
      postpartum.

PMID- 9537927
TI  - Fracture patterns at the Medieval Leper Hospital in Chichester.
AB  - Humans are constantly at risk of bone fractures, not only when threatened by
      personal violence, but also by the challenge of daily living. Because fractures
      are a cross-cultural phenomenon and are one of the more commonly observed
      skeletal lesions in archaeological collections, their presence provides a unique
      opportunity to compare living conditions, and thereby assess fracture risk in
      coexisting cultures. This study analyzed long bone fracture patterns of 212 sexed
      adults from the medieval leper hospital of St. James and St. Mary Magdalene in
      Chichester, England. The comparison of this hospital sample to other British
      medieval skeletal samples examined the level of health manifest in fracture
      etiology. The fracture frequency for this sample was 15.1%, with males accounting
      for 85.4% of the fractures. The fracture frequencies from the samples not
      affiliated with hospitals ranged from 3.3 to 5.6%. Because medieval urban
      lifestyle was notoriously difficult due to inadequate sanitation and living
      conditions, the overall health of the population at large was inferior, placing
      all at similar fracture risk. Therefore, more specific complications associated
      with the fractures were examined. Osseous modifications of the skeletons due to
      lepromatous leprosy were associated with 28% of individuals sustaining fractures.
      However, persons with the milder tuberculoid leprosy do not exhibit skeletal
      lesions, but are more prone to accident due to the earlier loss of sensory
      perception and visual impairment. It is argued that the presence of leprosy is
      underestimated in archaeological populations and may be a major contributing
      factor to the prevalence of fracture resulting from accidental falls.

PMID- 9537928
TI  - Growth patterns in the modern human skeleton.
AB  - This study investigates cross sectional growth patterns in the human skeleton
      using a recent skeletal sample of known age and sex. Measurements were selected
      to reflect different functional regions of the cranium, mandible and post cranial
      skeleton, and growth is evaluated using a single phase Gompertz curve. Different
      parts of the skeleton vary in the proportion of adult size attained at birth and
      in their subsequent rate of attainment of adult size. The paper introduces a
      method for the objective and quantitative comparison of the growth of different
      samples, and is used in this instance to analyze sexual differences in the growth
      of the post cranial skeleton. The development of sexual dimorphism is evaluated
      in terms of differences in the rate and duration of male and female growth. Adult
      sexual dimorphism is generally lower in early growing variables than in later
      growing variables. There is considerable diversity in the ontogenetic basis of
      sexual dimorphism in the human skeleton demonstrating that the development of
      sexual dimorphism within a species should not be regarded as a uniform
      phenomenon.

PMID- 9537929
TI  - Biomechanics of torsion in the human mandible.
AB  - Comparative investigations of mandibular function among primates have relied upon
      elementary structural models to estimate states of masticatory stress and strain.
      In these studies, mandibular corpus morphology is idealized as a homogeneous,
      isotropic symmetrical body of invariant geometry, and this morphological
      abstraction is used to infer relative levels of stress and strain in the jaw. In
      reality, none of the limiting conditions assumed by these models is satisfied;
      consequently, it is prudent to ask whether this "textbook" engineering approach
      is valid for the inference of biomechanical behavior. In this study, the
      predictions of various geometric representations of the mandibular corpus are
      evaluated against strains recorded in a sample of human jaws loaded in torsion.
      Symmetrical geometrical models (including various "robusticity" shape indices),
      although convenient, are probably not consistently reliable for predicting the
      distribution of strains in the corpus. The experimental data suggest that
      variations in cortical thickness within sections play a significant role in
      determining the profile of relative strains. For comparative applications,
      characterization of the corpus as an asymmetrical hollow ellipse (i.e., with
      differing thickness of medial and lateral cortical plates) may provide a
      reasonable portrayal of relative strains.

PMID- 9537930
TI  - Mandibular ramus flexure in an Indonesian population.

PMID- 9537931
TI  - Impact of the age at menarche on adult body composition in healthy pre- and
      postmenopausal women.
AB  - The present study focuses on the impact of age at menarche on body composition
      development during adulthood. With 459 healthy middle-class women between 18 and
      67 years (x = 41.5) the association between age at menarche and body composition
      was tested. Body composition, described by absolute and relative amount of fat
      mass, lean body mass, and bone mass, was estimated by means of dual energy x-ray
      absorptiometry. In order to exclude the influence of the menopausal transition on
      body composition, pre- and postmenopausal females were examined separately. The
      absolute amount of body fat was significantly lower within the group of women
      whose menarche occurred later. However, postmenopausal females exhibit less
      significant relations between the two trait systems than premenopausal women.
      This may be due to the impact of menopausal transition which affected the hormone
      levels and body composition development independently from the adolescent
      hormonal transition. While in both proband groups the quantitative amount of body
      fat was significantly related to menarcheal age, a significant relation between
      menarcheal age and adult body fat distribution could not be verified.

PMID- 9537932
TI  - Mandibular ramus flexure is a good indicator of sexual dimorphism.

PMID- 9537933
TI  - Type II tooth cusp occurrence asymmetry in a human monozygotic twin pair.
AB  - A Type II tooth cusp occurrence asymmetry proposed for human twins in 1974 but
      not observed until recently was described in a female monozygotic twin pair.

PMID- 9537934
TI  - Biological and virologic characteristics of primary HIV infection.
AB  - BACKGROUND: The clinical events surrounding acute HIV-1 infection have been well
      described, but little is known about whether the virologic course of acute HIV-1
      infection influences the subsequent progression of disease. OBJECTIVE: To define
      the virologic natural history of acute and very early HIV infection. DESIGN:
      Prospective, longitudinal cohort study. SETTING: University of Washington
      Research Clinic PARTICIPANTS: 74 adults enrolled soon after acquisition of HIV
      (mean, 69 days). MEASUREMENTS: Plasma HIV-1 RNA levels; quantitative cell
      cultures; CD4 cell counts; and detailed clinical assessments done at study entry,
      biweekly for 1 month, monthly for 2 months, and quarterly thereafter. RESULTS: In
      the first 30 days after acquisition of HIV, HIV-1 RNA levels varied greatly among
      participants (range, 27,200 to 1.6 x 10(6) copies per mL of plasma). Levels of
      HIV-1 RNA decreased by a mean of 6.5% per week for the first 120 days and then
      increased by a mean of 0.15% per week. CD4 cell counts decreased by a mean of 5.2
      cells/mm3 per week for the first 160 days and by a mean of 1.9 cells/mm3 per week
      thereafter (P < 0.01). Disease progressed faster in participants who sought
      medical care for their acute seroconversion syndrome (P = 0.01) and those who had
      high plasma HIV-1 RNA levels 120 to 365 days after acquisition (P < 0.01). Peak
      levels in the first 120 days were not predictive of disease progression.
      CONCLUSIONS: The variability in viral RNA levels associated with acute HIV-1
      infection is greater than previously appreciated. Within 120 days of acquisition,
      plasma HIV RNA levels rapidly decrease to an inflection point, after which they
      gradually increase. Virus-host interactions soon after acquisition seem to have a
      major influence on the long-term outcome of HIV-1 disease.

PMID- 9537935
TI  - The accuracy of substituted judgments in patients with terminal diagnoses.
AB  - BACKGROUND: Patients' loved ones often make end-of-life treatment decisions, but
      the accuracy of their substituted judgments and the factors associated with
      accuracy are poorly understood. OBJECTIVE: To assess the accuracy of judgments
      made by surrogate decision makers; ascertain the beliefs, practices, and clinical
      and sociodemographic factors associated with accuracy of surrogates' decisions;
      assess the preferences of patients for life-sustaining treatments; and compare
      differences in accuracy across diagnoses. DESIGN: Cross-sectional paired
      interviews. SETTING: Outpatient practices of three university hospitals.
      PATIENTS: 250 patients with terminal diagnoses of congestive heart failure, AIDS,
      amyotrophic lateral sclerosis, lung cancer, and chronic obstructive pulmonary
      disease (50 patient-surrogate pairs in each group) and 50 general medical
      patients and their surrogates. MEASUREMENTS: The accuracy of surrogate
      predictions was measured by using scales based on 10 potential treatments in each
      of three hypothetical clinical scenarios. RESULTS: Preferences varied according
      to mode of treatment and scenario. On average, surrogates made correct
      predictions in 66% of instances. Accuracy was better for the permanent coma
      scenario than for the scenarios of severe dementia or coma with a small chance of
      recovery (P < 0.001). In a binary logit model, the accuracy of substituted
      judgments was positively associated with the patient having spoken with the
      surrogate about end-of-life issues (odds ratio [OR], 1.9 [95% CI, 1.6 to 2.3]),
      the patient having private insurance (OR, 1.4 [CI, 1.1 to 1.7]), the surrogate's
      level of education (OR, 1.5 [CI, 1.2 to 1.9]), and the patient's level of
      education (OR, 1.7 [CI, 1.4 to 2.2]). Accuracy was negatively associated with the
      patient's belief that he or she would live longer than 10 years (OR, 0.6 [CI, 0.5
      to 0.7]), surrogate experience with life-sustaining treatment (OR, 0.4 [CI, 0.3
      to 0.5]), surrogate participation in religious services (OR, 0.67 [CI, 0.50 to
      0.91]), and a diagnosis of heart failure (OR, 0.6 [CI, 0.5 to 0.8]). Age,
      ethnicity, marital status, religion, and advance directives were not associated
      with accuracy. CONCLUSIONS: The accuracy of substituted judgments is associated
      with multiple clinically apparent patient and surrogate factors. This information
      can help clinicians identify conditions under which substituted judgments are
      likely to be accurate or inaccurate and can help target populations for education
      designed to improve the accuracy of surrogate decision making.

PMID- 9537936
TI  - Transesophageal echocardiography to assess embolic risk in patients with atrial
      fibrillation. ELAT Study Group. Embolism in Left Atrial Thrombi.
AB  - BACKGROUND: Transesophageal echocardiography visualizes the left atrium and its
      appendage, thrombi, and spontaneous echocardiographic contrast. OBJECTIVE: To
      assess the association of transesophageal echocardiographic characteristics with
      stroke or embolism in atrial fibrillation. DESIGN: Multicenter observational
      follow-up study. SETTING: Hospitals in Austria and Slovakia. PATIENTS: 409
      outpatients with nonrheumatic atrial fibrillation and without recent stroke.
      INTERVENTION: Patients with thrombi received anticoagulation, and patients
      without thrombi received aspirin. MEASUREMENTS: Primary events were stroke or
      embolism. Secondary events were death not caused by stroke or embolism and need
      for anticoagulation. RESULTS: In the left atrium or left atrial appendage, 10
      patients (2.5%) had thrombi and 47 (12%) had spontaneous echocardiographic
      contrast. The appendage had a mean (+/- SD) length of 44+/-10 mm, a mean width of
      23+/-6 mm, and a mean area of 5.8+/-2.5 cm2. Follow-up ranged from 1 to 74 months
      (mean, 58 months). Fifty patients had stroke or embolism, 53 died of a cause
      other than stroke or embolism, and 38 required anticoagulation. On univariate
      analysis, thrombi (risk ratio, 3.9 [95% CI, 1.4 to 10.1]; P = 0.009), length of
      the left atrial appendage (risk ratio, 1.6 [CI, 1.05 to 2.5]; P = 0.03), and
      width of the left atrial appendage (risk ratio, 2.4 [CI, 1.2 to 4.81; P = 0.01)
      were associated with stroke or embolism. Multivariate analysis identified
      hypertension (risk ratio, 3.6 [CI, 1.8 to 8.4]; P = 0.001), previous stroke (risk
      ratio, 3.7 [CI, 1.5 to 7.5]; P = 0.002), and age (risk ratio, 1.1 [CI, 1.0 to
      1.11; P < 0.001) as risk factors for stroke or embolism and provided evidence of
      an association between thrombi and stroke or embolism (risk ratio, 2.4 [CI, 0.9
      to 6.9]; P = 0.09). CONCLUSIONS: In outpatients with atrial fibrillation and
      without recent stroke, thrombi of the left atrium or left atrial appendage and
      length and width of the left atrial appendage were associated with stroke or
      embolism in univariate analysis. In a multivariate analysis, age, hypertension,
      and previous stroke were risk factors for stroke or embolism, and thrombi of the
      left atrium or left atrial appendage were possible risk factors. In these
      patients, history may be more useful than transesophageal echocardiography for
      the assessment of embolic risk.

PMID- 9537937
TI  - Transesophageal echocardiographic correlates of thromboembolism in high-risk
      patients with nonvalvular atrial fibrillation. The Stroke Prevention in Atrial
      Fibrillation Investigators Committee on Echocardiography.
AB  - BACKGROUND: Transesophageal echocardiography (TEE) visualizes potential sources
      of embolism in patients with atrial fibrillation, but the clinical significance
      of TEE findings has not been prospectively established. OBJECTIVE: To define TEE
      predictors of stroke in patients with atrial fibrillation and to examine response
      to antithrombotic therapy. DESIGN: Prospective correlation of TEE findings at
      study entry with subsequent ischemic stroke during 1.1-year mean follow-up of
      participants in a randomized trial. SETTING: 18 echocardiography laboratories.
      PATIENTS: 382 patients with atrial fibrillation at high risk for thromboembolism.
      INTERVENTION: Adjusted-dose warfarin (international normalized ratio, 2 to 3) or
      low-intensity warfarin (international normalized ratio, 1.2 to 1.5) plus aspirin
      (325 mg/d). MEASUREMENTS: Size of left atrium and left atrial appendage, flow
      velocity, spontaneous echocardiographic contrast, thrombus, and plaque on the
      aortic arch. RESULTS: 23 ischemic strokes occurred. In patients with dense
      spontaneous echocardiographic contrast (20%), the rate of stroke was 18.2% per
      year with combination therapy (2.9 times the rate in patients without this
      finding; P = 0.06) and 4.5% per year with adjusted-dose warfarin (P = 0.09 for
      rate reduction). Appendage thrombus, detected in 10% of patients, was associated
      with dense spontaneous echocardiographic contrast (P < 0.001), was seen more
      frequently after 2 weeks of combination therapy (15%) than after 2 weeks of
      adjusted-dose warfarin (4%) (P = 0.004), and tripled the overall rate of stroke
      (P = 0.04). Patients with complex aortic plaque (35%) had a fourfold increased
      rate of stroke compared with plaque-free patients (P = 0.005); adjusted-dose
      warfarin decreased risk by 75% (P = 0.02). Dense spontaneous echocardiographic
      contrast and complex aortic plaque were independent of each other as predictors
      of thromboembolism. CONCLUSIONS: In high-risk patients with atrial fibrillation,
      subsequent rates of thromboembolism are correlated with dense spontaneous
      echocardiographic contrast, thrombus of the atrial appendage, and aortic plaque.
      Adjusted-dose warfarin reduces the rate of stroke among patients with dense
      contrast and complex plaque. In patients with atrial fibrillation, the
      pathogenesis of stroke is multifactorial, and warfarin seems effective for the
      diverse mechanisms.

PMID- 9537938
TI  - Histologic and cytokine response to immunosuppression in giant-cell myocarditis.

PMID- 9537939
TI  - Developing and testing changes in delivery of care.

PMID- 9537940
TI  - The clinical behavior of localized and multicentric Castleman disease.
AB  - BACKGROUND: Castleman disease, an unusual condition of unknown cause consisting
      of a massive proliferation of lymphoid tissue, remains a clinicopathologic
      diagnosis. Three histologic variants (hyaline vascular, plasma-cell, and mixed)
      and two clinical types (localized and multicentric) of Castleman disease have
      been described. OBJECTIVE: To analyze the clinical features, management, and
      outcome of patients with Castleman disease. DESIGN: Case series. SETTING:
      University referral hospitals. PATIENTS: All patients with Castleman disease who
      were seen at Texas Medical Center, Houston, Texas, between 1977 and 1995.
      INTERVENTIONS: Surgical excision for localized disease; surgery, combination
      chemotherapy, or prednisone for multicentric disease. MEASUREMENTS: Patients were
      identified according to initial presentation as having localized or multicentric
      Castleman disease. Patients within each group were further subdivided according
      to whether they had hyaline vascular, plasma-cell, or mixed disease. RESULTS:
      Data from 15 patients were analyzed. All 7 patients with localized disease
      underwent surgical excision and remain free of disease. The 8 patients with
      multicentric disease were further subdivided according to initial treatment:
      Three patients who received combination chemotherapy are currently alive and free
      of disease; 2 patients treated with prednisone are alive but have needed
      intermittent maintenance therapy for disease reactivations; and 2 patients
      treated with surgery only have died, 1 of infectious complications and 1 of non
      Hodgkin lymphoma. CONCLUSIONS: Localized and multicentric Castleman disease are
      different clinical disorders with overlapping histologic features. Localized
      disease can be cured with surgery, but complete remissions in patients with
      multicentric disease have been achieved only with chemotherapy or prednisone
      given at the time of diagnosis.

PMID- 9537941
TI  - Noninvasive diagnosis of deep venous thrombosis. McMaster Diagnostic Imaging
      Practice Guidelines Initiative.
AB  - PURPOSE: To review noninvasive methods for diagnosis of first and recurrent deep
      venous thrombosis and provide evidence-based recommendations for the diagnosis of
      deep venous thrombosis in symptomatic, asymptomatic, and pregnant patients. DATA
      SOURCES: Accuracy (comparison with contrast venography) and management (safety of
      withholding anticoagulants when results were normal) studies that evaluated tests
      for diagnosis of deep venous thrombosis were identified from a MEDLINE search,
      personal files, and bibliographies of reviews and original studies. STUDY
      SELECTION: Prospective cohort studies (accuracy and management studies) and
      randomized comparisons (management studies) that satisfied predefined
      methodologic criteria were included. DATA EXTRACTION: Sensitivity, specificity,
      and positive and negative predictive values were determined for accuracy studies.
      Rates of venous thromboembolism during long-term follow-up of patients with
      normal results were determined for management studies. DATA SYNTHESIS: Data from
      individual studies were combined under a random-effects model. The accuracy of
      noninvasive tests was compared, with emphasis on within-study comparisons.
      Recommendations for diagnosis of deep venous thrombosis were developed by a
      multidisciplinary group and graded according to the strength of the supporting
      evidence. Venous ultrasonography is the most accurate noninvasive test for the
      diagnosis of a first symptomatic proximal deep venous thrombosis. However,
      neither ultrasonography nor impedance plethysmography is accurate in asymptomatic
      postoperative patients. Venous ultrasonography is less accurate for symptomatic
      isolated distal (calf) deep venous thrombosis than for proximal deep venous
      thrombosis, and the clinical utility of venous ultrasonography of the distal
      veins is uncertain. Withholding anticoagulant therapy in symptomatic patients
      with suspected deep venous thrombosis who have normal results on serial venous
      ultrasonography or impedance plethysmography is safe. Diagnosis of recurrent deep
      venous thrombosis requires evidence of new thrombus formation, such as a new
      noncompressible venous segment detected by venous ultrasonography, conversion of
      a normal result on impedance plethysmography to abnormal, or presence of an
      intraluminal filling defect on venography. Suspected deep venous thrombosis in
      pregnant patients can usually be managed with serial venous ultrasonography or
      impedance plethysmography. In symptomatic patients with a suspected first episode
      of deep venous thrombosis, clinical assessment and D-dimer testing are
      complementary to testing with venous ultrasonography and impedance
      plethysmography. CONCLUSIONS: Patients with suspected deep venous thrombosis can
      usually be managed with noninvasive testing. However, if the results of this
      testing are nondiagnostic or are discordant with the clinical assessment,
      venography should be considered.

PMID- 9537942
TI  - Understanding the fraud and abuse laws: guidance for internists. American College
      of Physicians.

PMID- 9537943
TI  - Transesophageal echocardiography and atrial fibrillation: added value or
      expensive toy?

PMID- 9537944
TI  - Cutting waste and keeping faith.

PMID- 9537945
TI  - Brignole.

PMID- 9537946
TI  - Perioperative cardiac risk assessment and management.

PMID- 9537947
TI  - Perioperative cardiac risk assessment and management.

PMID- 9537948
TI  - Angiotensin-converting enzyme inhibitors in nondiabetic renal disease.

PMID- 9537949
TI  - Hepatitis C and B-cell lymphoma.

PMID- 9537950
TI  - Social class and recovery from myocardial infarction.

PMID- 9537951
TI  - Botulinum toxin in long-term therapy for achalasia.

PMID- 9537952
TI  - Aspirin in the management of recurrent herpes simplex virus infection.

PMID- 9537953
TI  - Quantitative assessment of hepatitis B virus DNA during a 24-week course of
      lamivudine therapy.

PMID- 9537954
TI  - Medicine: a caring profession?

PMID- 9537955
TI  - Notice: overlapping publication.

PMID- 9537956
TI  - Time.

PMID- 9537957
TI  - Time.

PMID- 9537958
TI  - A registry for clinical trials.

PMID- 9537959
TI  - Epilepsy treatment enters a new era.

PMID- 9537961
TI  - Coma and confusional states: emergency diagnosis and management.
AB  - Coma and confusion signal a failure of brain function with many possible causes.
      Since many of the potential causes may quickly lead to death or severe
      disability, it is important to develop a focused and ordered approach to
      facilitate the rapid diagnosis and early institution of proper therapies. This
      requires an understanding of the localizing features of the neurologic
      examination and of the syndromes likely to cause coma and confusion, a
      predetermined plan for empiric therapies in certain cases of doubt when
      diagnostic confirmation will be delayed, and a careful consideration of cases
      when the diagnosis is not revealed by the initial neuroimaging, lumbar puncture,
      or EEG.

PMID- 9537960
TI  - Identification of the structural similarity in the functionally related
      amidohydrolases acting on the cyclic amide ring.
AB  - The functionally related amidohydrolases, including D-hydantoinases,
      dihydropyrimidinases, allantoinases and dihydro-orotases, share a similar
      catalytic function of acting on the cyclic amide ring. We aligned 16
      amidohydrolases by taking account of the conservative substitution and found a
      number of highly conserved regions and invariant amino acid residues. Analyses of
      the secondary structure and hydropathy profile of the enzymes revealed a
      significant degree of similarity in the conserved regions. Among the regions, the
      long stretched region I is of particular interest, because it is mainly composed
      of invariant amino acid residues, showing a similarity of 69% for the enzymes. A
      search of the protein data bank using the sequence of the conserved region I
      identified a number of proteins possessing a similar catalytic property,
      providing a clue that this region might be linked with the catalytic function. As
      a particular sequence, one aspartic acid and four histidine residues are found to
      be rigidly conserved in the functionally related amidohydrolases. In order to
      investigate the significance of the conserved residues, site-directed mutagenesis
      was carried out typically for the D-hydantoinase gene cloned from Bacillus
      stearothermophilus SD1. These residues were found to be essential for metal
      binding as well as catalysis, strongly implying that these invariant residues
      play a critical role in other enzymes as well as in D-hydantoinase. On the basis
      of the similar catalytic function and existence of the rigidly conserved
      sequence, we propose a close evolutionary relationship among the functionally
      related amido hydrolases, including D-hydantoinase, dihydropyrimidinase,
      allantoinase and dihydroorotase.

PMID- 9537962
TI  - Seizures.
AB  - Seizures are one of the most common neurologic emergencies. This article reviews
      the emergency evaluation and treatment of seizures, including status epilepticus.
      Pseudoseizures related to drugs, alcohol, and pregnancy are also discussed.

PMID- 9537963
TI  - Emergency department evaluation of headache.
AB  - Headache is an extremely common complaint in the Emergency Department, accounting
      for up to 16% of all visits. Although there are more than 300 medical conditions
      which can produce headache, the vast majority of headache disorders are benign.
      This article outlines an orderly approach for evaluating patients who present
      with headaches; in addition, the authors discuss the emergency treatment of the
      more common types of headache.

PMID- 9537964
TI  - Dizziness: neurological emergencies.
AB  - A patient's medical history provides the key information for deciding on the type
      of dizziness and its likely cause. First, one must separate vestibular from non
      vestibular causes of dizziness to determine the focus of the diagnostic work-up.
      Of the common causes of vertigo, benign positional vertigo can be reliably
      diagnosed and cured at the bedside. One of the few instances where neuroimaging
      is required on an emergent basis is for a patient presenting with acute vertigo
      and profound imbalance likely to be a cerebellar hemorrhage or infarct.
      Antivertiginous and anti-emetic drugs can provide relief of acute vertigo and
      nausea, but medications should be rapidly tapered to allow compensation to occur.

PMID- 9537965
TI  - Acute visual loss and other disorders of the eyes.
AB  - This article outlines neuro-ophthalmic findings and diseases which may present in
      an emergency setting. The abnormal optic disc, visual loss, double-vision and
      disorders of gaze, skew deviation, and the neuro-ophthalmology of vascular
      lesions, intracerebral hemorrhage, increased intracranial pressure, neuromuscular
      emergencies, metabolic disturbances, and trauma are all reviewed.

PMID- 9537966
TI  - Ischemic stroke.
AB  - Acute ischemic stroke is a neurological emergency that requires ultra-rapid
      intervention. Stroke teams and stroke protocols can be devised to expediate
      evaluation and treatment. In carefully selected patients, thrombolytic therapy
      offers a significant benefit but must be initialized within 3 hours of stroke
      onset. Emerging alternative strategies for reperfusion and neuroprotection must
      also be initiated during the hyperacute period. The role of more traditional
      therapies, such as antiplatelet agents and anticoagulants, have been better
      defined through several recent major clinical trials.

PMID- 9537967
TI  - Intracranial hemorrhage: diagnosis and emergency management.
AB  - Intracranial hemorrhages are an important cause of acute neurologic disease
      presenting in the emergency setting. To optimize outcome, it is important that
      the physician quickly recognize intracranial hemorrhages. To minimize mortality
      and neurologic morbidity, it is often necessary to initiate urgent therapy in the
      emergency rooms and to obtain neurosurgical consultation in order to pursue early
      surgical therapy. This article discusses the recognition and early treatment of
      the various types of intracranial hemorrhages.

PMID- 9537968
TI  - Neuromuscular disorders and acute respiratory failure.
AB  - This article discusses the assessment and management of rapidly progressive
      weakness due to neuromuscular disorders. The authors review elements helpful in
      determining the causes of weakness including pertinent history and laboratory
      studies. Disorders are classified according to the level of the motor unit
      involved and triage/management decisions are described. In addition, respiratory
      function assessment is reviewed. The latter part of this article is devoted to
      evaluation and management of two of the most common disorders, Guillain-Barre
      syndrome and myasthenia gravis.

PMID- 9537969
TI  - Infections of the nervous system.
AB  - Epidemiologic trends causing infections of the nervous system remain a
      significant source of morbidity and mortality one half-century after the
      introduction of penicillin. This article outlines common causes of bacterial
      meningitis, aseptic meningitis syndrome, encephalitis, abscess, spinal cord
      syndromes, and cranial and peripheral nerve problems. Recommendations for
      diagnostic evaluation and both empiric and definitive antimicrobial therapy are
      offered; controversial management issues are also discussed. The protean
      manifestations of varicella-zoster virus and Lyme diseases are outlined. In
      addition, special considerations in the immunocompromised host, including organ
      transplant recipients, cancer patients, and HIV-positive persons are explained,
      and antimicrobial therapy is discussed.

PMID- 9537970
TI  - Neurologic emergencies in cancer patients.
AB  - Neurologic emergencies are common among cancer patients and their incidence is
      increasing as patients live longer as a result of improved antineoplastic
      therapy. This article reviews acute neurologic complications in cancer patients.
      Among those complications reviewed are brain metastases, epidural spinal cord
      compression, leptomeningeal metastases, cerebrovascular disorders, complications
      of antineoplastic therapy, and paraneoplastic syndromes.

PMID- 9537972
TI  - Acute neurologic complications of drug and alcohol abuse.
AB  - Recreationally abused substances include both legal and illegal agents, broadly
      classified as opioids, psychostimulants, sedatives, cannabis (marijuana),
      hallucinogens, inhalants, dissociative anesthetics (phencyclidine),
      anticholinergics, ethanol, and tobacco. These substances are associated with an
      array of neurological emergencies resulting from overdose, withdrawal, and other
      medical and neurological complications.

PMID- 9537971
TI  - Head and spinal cord injury.
AB  - Traumatic brain and spinal cord injuries remain the leading cause of death and
      disability for individuals under 50 years of age. This article describes common
      causes of primary and secondary central nervous system injuries. Particular
      emphasis is placed on the initial evaluation of trauma patients, detection of
      head and spinal cord injuries, and critical care of these patients. Definitive
      management of central nervous system injuries and prognosis and long-term
      management issues are also discussed.

PMID- 9537973
TI  - Psychiatric and behavioral problems.
AB  - In an emergency setting, many neurologic conditions present with psychiatric and
      behavioral symptoms. These symptoms may either be the first manifestation of the
      neurologic illness or a later occurrence in the progression of the disease. It is
      important for clinicians evaluating patients with psychiatric symptoms to
      identify the signs indicating associated neurologic illness and to have
      strategies for managing the acute, potentially dangerous, neuropsychiatric
      manifestations of the disease. This article addresses emergency evaluation and
      management of depression, anxiety, psychosis, mania, suicide attempts,
      neuroleptic malignant syndrome and other hypermetabolic and amnestic syndromes,
      somatoform disorders, aggression, and legal issues, such as capacity to accept or
      refuse treatment.

PMID- 9537974
TI  - The gynecologic oncology model: research.
AB  - Research in gynecologic oncology has been increasingly emphasized over the last
      decade. The formal training within this subspecialty has expanded to include
      quality research, both clinical and laboratory science, as an integral part.
      There have also been recent major advances in the laboratory and clinical based
      understanding of the genetics, biology, and treatment of gynecologic cancers.
      Despite the fiscal constraints of the 1990s that have impacted the ability of the
      clinician scientist to balance the responsibilities of research, teaching, and
      patient care, there are ongoing attempts to improve the research environment for
      physician scientists in this field.

PMID- 9537975
TI  - Screening for gynecologic cancer.
AB  - Screening for cancer of the uterus, cervix, and ovary allows earlier detection of
      disease in some asymptomatic women. The screening tests commonly used have low
      false-negative rates and, with the exception of endometrial biopsy and
      endometrial washings in detection of uterine cancer, they have high false
      positive rates. Conclusions concerning effectiveness of screening tests in
      improving the likelihood of a favorable outcome are difficult because there are
      no randomized trials. Without randomized trials, cost-benefit analysis of
      screening for gynecologic malignancies is imprecise.

PMID- 9537976
TI  - Endometrial cancer: current concepts and management.
AB  - Endometrial cancer is the most common pelvic gynecologic cancer in women. Its
      occurrence is associated with endometrial hyperplasia, unapposed estrogen
      therapy, and more recently, tamoxifen. The staging uses information obtained at
      the time of surgery. Hysterectomy continues to be the primary treatment for most
      patients with endometrial cancer, whereas postoperative radiation therapy is used
      in the treatment of patients with other than low-risk prognostic factors.

PMID- 9537977
TI  - Controversies in benign breast disease.
AB  - Breast health means more than breast cancer. At least 50% of patients seen at a
      multidisciplinary breast center have benign conditions. Pain, nipple discharge,
      and a question of a mass are the usual chief complaints. This article provides
      contemporary information and management guidelines for the common breast
      conditions associated with these complaints.

PMID- 9537978
TI  - Cervical cancer.
AB  - Despite the development of cervical cytology, cancer of the cervix continues to
      be a major health problem for women. The cause, diagnostic, and therapeutic
      management of women with preinvasive and invasive disease is discussed.

PMID- 9537979
TI  - Ovarian cancer.
AB  - Ovarian cancer is the leading cause of death in women with pelvic malignancies.
      Because of the multiple histologic types of malignancy that can arise within the
      ovary, accurate diagnosis and staging is critical for optimal patient care. The
      current standard of proper surgical management followed by combination
      chemotherapy is outlined. In addition, risk factors, screening, prognostic
      factors, and the approach to the relapsed patient is discussed.

PMID- 9537980
TI  - Vulvar cancer.
AB  - Historically, nearly all vulvar cancer is managed by ultraradical surgery.
      Currently, individualized and more surgically conservative approaches achieve
      equivalent outcomes with far less morbidity and cosmetic disfiguration.
      Microinvasive disease can be cured with local excision only. Lateral lesions are
      usually managed with local excision and ipsilateral groin node dissection only.
      Advanced disease responds remarkably to chemoradiation.

PMID- 9537981
TI  - Primary vaginal cancer.
AB  - Vaginal cancer, 2% of all female genital malignancies, has a worse prognosis than
      cervical cancer. Squamos cell carcinoma, the most common histologic subtype, may
      be associated partly with human papillomavirus. Most patients present with
      vaginal bleeding and discharge. Radiation or surgery are the main treatment
      modalities, but the physical and psychosexual morbidity can be significant.

PMID- 9537982
TI  - Fallopian tube carcinoma.
AB  - Primary fallopian tube carcinoma represents less than 1% of all gynecologic
      malignancies and is therefore one of the less common malignancies of the female
      genital tract. Fallopian tube carcinoma is rarely diagnosed preoperatively and is
      often mistaken for benign pelvic disease or ovarian cancer. Compared with ovarian
      carcinoma, fallopian tube cancer more often presents in early stage but seems to
      have a worse prognosis, stage for stage. Treatment consists of surgical debulking
      followed by chemotherapy, adjuvant or otherwise. New studies are needed to better
      delineate the clinical course, prognostic factors, and appropriate chemotherapy
      recommendations.

PMID- 9537983
TI  - Cancer in pregnancy.
AB  - Cancer in pregnancy requires the careful consideration of multiple complex issues
      to achieve the most favorable outcome for mother and fetus. Presented are the
      principles of surgery, radiation, and chemotherapy as they pertain to pregnancy,
      and a discussion of site-specific cancers.

PMID- 9537984
TI  - Pelvic radical surgery.
AB  - The management of gynecological malignancies is dictated by the stage and nature
      of the disease. Often, the optimal treatment requires radical pelvic surgery.
      This is especially true in cervical, ovarian, and vulvar carcinoma. Radical
      hysterectomy, exenterative procedures and tumor debulking comprise the
      armamentarium of gynecological oncologists. This article attempts to review the
      different surgical strategies with attention to their respective indications,
      potential complications, and overall efficacy.

PMID- 9537985
TI  - Binding of 2-azaanthraquinone derivatives to DNA and their interference with the
      activity of DNA topoisomerases in vitro.
AB  - We have investigated the binding ability to DNA of compounds belonging to the 2
      azaanthraquinone-type structure and have examined the effect on the activity of
      DNA gyrase as well as on mammalian topoisomerases in vitro. Using different
      biophysical techniques it was found that one of these ligands, 9-((2
      dimethylamino)ethyl)amino)-6-hydroxy-7-methoxy-5, 10
      dihydroxybenzo[g]isoquinoline-5,10-dione (TPL-I), is an intercalating DNA binding
      agent, whereas the parent compound tolypocladin (TPL) and a derivative (TPL-II)
      showed almost no similar affinity to DNA. CD measurements demonstrated a
      significant and selective binding tendency of TPL-I to alternating
      purine/pyrimidine sequences with some preference for poly(dA-dT). poly(dA-dT). Tm
      values were increased of the ligand complex with the alternating AT-containing
      duplex polymer. The binding to various DNAs was characterized by CD and visible
      absorption spectral changes. From the latter, different binding constants of 6.2
      x 10(5) and 1.5 x 10(5) M-1 were obtained for poly(dA-dT).poly(dA-dT) and
      poly(dA). poly(dT), respectively. Sedimentation measurements with supercoiled
      pBR322 plasmid DNA clearly indicated an intercalative binding mechanism
      associated with an unwinding angle of about 18 degrees. These results suggest
      that the intercalative binding of TPL-I is promoted by the 2
      (dimethylamino)ethylamino group substituted on carbon 9 of the anthraquinone
      system. The cytotoxic compound TPL-I, but not TPL or TPL-II, effectively
      inhibited the DNA supercoiling reaction of DNA gyrase and the activity of
      mammalian topoisomerases I and II as measured by the relaxation assay. TPL-I
      affects the cleavage reaction of topoisomerases on a single site located in
      alternating purine-pyrimidine sequence regions. The inhibitory potency of TPL-I
      can be ascribed to a blocking of cleavage sites on the DNA substrate, which
      correlates with the sequence preference of the ligand.

PMID- 9537986
TI  - The solution structure of type II antifreeze protein reveals a new member of the
      lectin family.
AB  - A recombinant form of the sea raven type II antifreeze protein (SRAFP) has been
      produced using the Pichia pastoris expression system. The antifreeze activity of
      recombinant SRAFP is indistinguishable from that of the wild-type protein. The
      global fold of SRAFP has been determined by two-dimensional 1H homonuclear and
      three-dimensional 1H-?15N? heteronuclear NMR spectroscopy using 785 NOE distance
      restraints and 47 angular restraints. The molecule folds into one globular domain
      that consists of two helices and nine beta-strands in two beta-sheets. The
      structure confirms the proposed existence of five disulfide bonds. The global
      fold of SRAFP is homologous to C-type lectins and pancreatic stone proteins, even
      though the sequence identity is only approximately 20%.

PMID- 9537987
TI  - Crystal structure of Y34F mutant human mitochondrial manganese superoxide
      dismutase and the functional role of tyrosine 34.
AB  - Tyrosine 34 is a prominent and conserved residue in the active site of the
      manganese superoxide dismutases in organisms from bacteria to man. We have
      prepared the mutant containing the replacement Tyr 34 --> Phe (Y34F) in human
      manganese superoxide dismutase (hMnSOD) and crystallized it in two different
      crystal forms, orthorhombic and hexagonal. Crystal structures of hMnSOD Y34F have
      been solved to 1.9 A resolution in a hexagonal crystal form, denoted as Y34Fhex,
      and to 2.2 A resolution in an orthorhombic crystal form, denoted as Y34Fortho.
      Both crystal forms give structures that are closely superimposable with that of
      wild-type hMnSOD, with the phenyl rings of Tyr 34 in the wild type and Phe 34 in
      the mutant very similar in orientation. Therefore, in Y34F, a hydrogen-bonded
      relay that links the metal-bound hydroxyl to ordered solvent (Mn-OH to Gln 143 to
      Tyr 34 to H2O to His 30) is broken. Surprisingly, the loss of the Tyr 34 hydrogen
      bonds resulted in large increases in stability (measured by Tm), suggesting that
      the Tyr 34 hydroxyl does not play a role in stabilizing active-site architecture.
      The functional role of the side chain hydroxyl of Tyr 34 can be evaluated by
      comparison of the Y34F mutant with the wild-type hMnSOD. Both wild-type and Y34F
      had kcat/Km near 10(9) M-1 s-1, close to diffusion-controlled; however, Y34F
      showed kcat for maximal catalysis smaller by 10-fold than the wild type. In
      addition, the mutant Y34F was more susceptible to product inhibition by peroxide
      than the wild-type enzyme. This activity profile and the breaking of the hydrogen
      bonding chain at the active site caused by the replacement Tyr 34 --> Phe suggest
      that Tyr 34 is a proton donor for O2* - reduction to H2O2 or is involved
      indirectly by orienting solvent or other residues for proton transfer. Up to 100
      mM buffers in solution failed to enhance catalysis by either Y34F or the wild
      type hMnSOD, suggesting that protonation from solution cannot enhance the release
      of the inhibiting bound peroxide ion, likely reflecting the enclosure of the
      active site by conserved residues as shown by the X-ray structures. The increased
      thermostability of the mutant Y34F and equal diffusion-controlled activity of
      Y34F and wild-type enzymes with normal superoxide levels suggest that
      evolutionary conservation of active-site residues in metalloenzymes reflects
      constraints from extreme rather than average cellular conditions. This new
      hypothesis that extreme rather than normal substrate concentrations are a
      powerful constraint on residue conservation may apply most strongly to enzyme
      defenses where the ability to meet extreme conditions directly affects cell
      survival.

PMID- 9537988
TI  - Probing the active site of human manganese superoxide dismutase: the role of
      glutamine 143.
AB  - Structural and biochemical characterization of the nonliganding residue glutamine
      143 near the manganese of human Mn superoxide dismutase (hMnSOD), a homotetramer
      of 22 kDa, reveals a functional role for this residue. In the wild-type protein,
      the side-chain amide group of Gln 143 is about 5 A from the metal and is hydrogen
      bonded to Tyr 34, which is a second prominent side chain adjacent to the metal.
      We have prepared the site-specific mutant of hMnSOD with the conservative
      replacement of Gln 143 --> Asn (Q143N). The crystal structure of Q143N shows that
      the side-chain amide nitrogen of residue 143 is 1.7 A more distant from the
      manganese than in the wild-type enzyme. The Tyr 34 side-chain hydroxyl in Q143N
      is also moved to become 0.6 A more distant from the metal due to an additional
      water molecule. Differential scanning calorimetry showed that Q143N is slightly
      more stable than the wild-type enzyme with Tm for the main unfolding transition
      increased by 2 degrees C to 90.7 degrees C. Pulse radiolysis and stopped-flow
      spectrophotometry reveal that unlike wild-type hMnSOD, which is strongly
      inhibited by peroxide, Q143N MnSOD exhibits no product inhibition even at
      concentrations of O2. - in the millimolar range, and its catalysis follows
      Michaelis kinetics with no evidence of cooperativity. However, the overall
      catalytic activity of this mutant was decreased 2-3 orders of magnitude compared
      with the wild-type MnSOD, which can account for its lack of product inhibition.
      Q143N MnSOD lacked the visible absorption spectrum typical of wild-type
      Mn(III)SOD. Also, unlike the wild-type Mn(III)SOD, which is electron paramagnetic
      resonance (EPR) silent, Q143N MnSOD has a complex EPR spectrum with many
      resonances in the region below 2250 G. We conclude that the Gln 143 --> Asn
      mutation has increased the reduction potential of manganese to stabilize Mn(II),
      indicating that Gln 143 has a substantial role in maintaining a reduction
      potential favorable for the oxidation and reduction cycles in the catalytic
      disproportionation of superoxide. A solvent hydrogen isotope effect near 2 for
      kcat in catalysis by Q143N hMnSOD indicates rate-contributing proton transfers to
      form product hydroperoxide anion or hydrogen peroxide. The data demonstrate a
      prominent role for Gln 143 in maintaining the microenvironment of the manganese
      and in efficient catalysis of superoxide dismutation to oxygen and hydrogen
      peroxide.

PMID- 9537989
TI  - Structural studies of wild-type and mutant reaction centers from an antenna
      deficient strain of Rhodobacter sphaeroides: monitoring the optical properties of
      the complex from bacterial cell to crystal.
AB  - Reaction centers have been crystallized from the antenna-deficient RCO2 strain of
      Rhodobacter sphaeroides, and a structural model has been constructed at 2.6 A
      resolution. The antenna-deficient strain allows assessment of the structural
      integrity of the reaction center at each stage in the purification
      crystallization procedure. Spectroscopic evidence indicates that the properties
      of the reaction center bacteriopheophytins and the primary donor
      bacteriochlorophylls are modified somewhat on removal of the protein complex from
      the membrane and that these changes are carried through to the crystal form of
      the reaction center. The structure of a FM197R/YM177F mutant reaction center has
      also been determined to 2.55 A resolution. The mutant complex shows an unexpected
      change in structure, with a significant reorientation of the new arginine, the
      incorporation of a new water molecule into the structure, and rotation of the 2
      acetyl carbonyl group of one of the primary donor bacteriochlorophylls to a more
      out-of-plane geometry. Changes in the optical spectrum of the FM197R/YM177F
      reaction center are discussed with respect to the altered structure of the
      complex.

PMID- 9537990
TI  - Exploring the cellulose/xylan specificity of the beta-1,4-glycanase cex from
      Cellulomonas fimi through crystallography and mutation.
AB  - The retaining beta-1,4-glycanase Cex from Cellulomonas fimi, a family 10 glycosyl
      hydrolase, hydrolyzes xylan 40-fold more efficiently than cellulose. To gain
      insight into the nature of its preference for xylan, we determined the crystal
      structure of the Cex catalytic domain (Cex-cd) trapped as its covalent 2-deoxy-2
      fluoroxylobiosyl-enzyme intermediate to 1.9 A resolution. Together with the
      crystal structure of unliganded Cex-cd [White, A., et al. (1994) Biochemistry 33,
      12546-12552] and the previously determined crystal structure of the covalent 2
      deoxy-2-fluorocellobiosyl-Cex-cd intermediate [White, A., et al. (1996) Nat.
      Struct. Biol. 3, 149-154], this structure provides a convincing rationale for the
      observed substrate specificity in Cex. Two active site residues, Gln87 and
      Trp281, are found to sterically hinder the binding of glucosides and must
      rearrange to accommodate these substrates. Such rearrangements are not necessary
      for the binding of xylobiosides. The importance of this observation was tested by
      examining the catalytic behavior of the enzyme with Gln87 mutated to Met. This
      mutation had no measurable effect on substrate affinity or turnover number
      relative to the wild type enzyme, indicating that the Met side chain could
      accommodate the glucoside moiety as effectively as the wild type Gln residue.
      Subsequent mutagenesis studies will address the role of entropic versus enthalpic
      contributions to binding by introducing side chains that might be more rigid in
      the unliganded enzyme.

PMID- 9537991
TI  - Site-specific phosphorylation of Lys-Ser-Pro repeat peptides from neurofilament H
      by cyclin-dependent kinase 5: structural basis for substrate recognition.
AB  - Recent work has shown that high molecular weight neurofilament (NF) proteins are
      phosphorylated in their carboxy-terminal tail portion by the enzyme cyclin
      dependent kinase 5 (CDK-5). The tail domain of neurofilaments contains 52
      tripeptide repeats, viz. Lys-Ser-Pro, which mainly exist as KSPXK and KSPXXX
      motifs (X = amino acid). CDK-5 specifically phosphorylates the serine residues
      within the KSPXK sites. We probed the structural basis for this type of substrate
      selectivity by studying the conformation of synthetic peptides containing either
      KSPXK or KSPXXX repeats designed from native neurofilament sequences. Synthetic
      peptides with KSPXK repeats were phosphorylated on serine with a recombinant CDK
      5/p25 complex whereas those with KSPXXX repeats were unreactive in this system.
      Circular dichroism (CD) studies in 50% TFE/H2O revealed a predominantly helical
      conformation for the KSPXXX-containing peptides, whereas the CD spectra for KSPXK
      containing peptides indicated the presence of a high population of extended
      structures in water and 50% TFE solutions. However, detailed NMR analysis of one
      such peptide which included two such KSPXK repeats suggested a turn-like
      conformation encompassing the first KSPXK repeat. Restrained molecular dynamics
      calculations yielded an unusually stable, folded structure with a double "S"-like
      bend incorporating the central residues of the peptide. The data suggest that a
      transient reverse turn or loop-type structure may be a requirement for CDK-5
      promoted phosphate transfer to neurofilament-specific peptide segments.

PMID- 9537992
TI  - Structural evidence for the presence of a secondary calcium binding site in human
      alpha-lactalbumin.
AB  - The high-resolution X-ray crystal structure of human alpha-lactalbumin (at 1.8 A)
      in the presence of an elevated level of calcium reveals a new secondary calcium
      binding site, 7.9 A away from the primary calcium binding site known in all alpha
      lactalbumin structures so far. The new calcium binding site is different from the
      zinc and sulfate binding sites [Ren, J., et al. (1993) J. Biol. Chem. 268, 19292
      19298] but shares common features with the manganese binding site as described by
      Gerkin [Gerkin, T. A. (1984) Biochemistry 23, 4688-4697]. The proximity of the
      manganese and calcium binding region and the location of the functional site on
      one side of the charged surface of the alpha-lactalbumin molecule suggest that
      these binding sites might play a role in the formation of the lactose synthase
      complex.

PMID- 9537993
TI  - Kinetic and mass spectrometric analyses of the interactions between plant
      acetohydroxy acid isomeroreductase and thiadiazole derivatives.
AB  - Plant acetohydroxy acid isomeroreductase (EC 1.1.1.86), the second enzyme of the
      branched chain amino acid biosynthetic pathway, has been submitted to high
      throughput screening for herbicide discovery. We report here the discovery of a
      new class of compounds belonging to the thiadiazole family, which exhibit a
      strong inhibitory effect on this plant enzyme. Kinetic analyses revealed that
      these compounds act as either reversible or irreversible noncompetitive
      inhibitors of the plant enzyme. Reversibility or irreversibility of these
      compounds can be attributed to the nature of the additional groups of the
      thiadiazole ring favoring or not favoring the formation of a covalent adduct.
      Mass spectrometric experiments on the complex between an irreversible compound
      belonging to the thiadiazole family and the plant enzyme identified Cys498 as the
      binding site of the inhibitor.

PMID- 9537994
TI  - G protein-bound conformation of mastoparan-X: heteronuclear multidimensional
      transferred nuclear overhauser effect analysis of peptide uniformly enriched with
      13C and 15N.
AB  - Mastoparans, a family of tetradecapeptides from wasp venom, have been used as
      convenient low molecular weight models of receptors coupled to GTP-binding
      regulatory proteins (G proteins) for the understanding of the interaction between
      G proteins and receptors. Sukumar and Higashijima have analyzed the conformation
      of mastoparan-X (MP-X) bound to the G protein alpha-subunit using proton two
      dimensional transferred nuclear Overhauser effect (TRNOE) spectroscopy [Sukumar,
      M., and Higashijima, T. (1992) J. Biol. Chem., 267, 21421-21424]. The resultant
      structure, however, was not well-defined due to severe overlap of peptide proton
      resonances. To determine the G protein-bound conformation of MP-X in detail, we
      have analyzed this interaction by heteronuclear multidimensional TRNOE
      experiments of MP-X uniformly enriched with 15N and/or 13C. By solving the
      overlap problem, we were able to determine the precise conformation of MP-X bound
      to Gi1alpha: the peptide adopts an amphiphilic alpha-helix from Trp3 to C
      terminal Leu14, and the atomic root-mean-square deviation (rmsd) values in this
      portion about the averaged coordinates were 0.27 +/- 0.07 A for the backbone
      atoms (N, Calpha, C') and 0.84 +/- 0.16 A for all heavy atoms. These values are
      much smaller than the corresponding rmsd values of the structures obtained from
      the proton 2D TRNOE spectrum alone: 1.70 +/- 0.41 A for the backbone atoms (N,
      Calpha, C') and 2.84 +/- 0.51 A for all heavy atoms. Our results indicate that
      the heteronuclear multidimensional TRNOE experiments of peptides uniformly
      enriched with stable isotopes are a very powerful tool for analyzing the
      conformation of short peptides bound to large proteins. We will also discuss the
      structure-activity relationships of mastoparans in activating G proteins on the
      basis of the precise structure of MP-X bound to Gi1alpha.

PMID- 9537995
TI  - Characterization of dimethylargininase from bovine brain: evidence for a zinc
      binding site.
AB  - Dimethylargininase (EC 3.5.3.18) is involved in the regulation of the levels of
      the natural occurring free arginine derivatives L-Nomega,Nomega-dimethylarginine
      and L-Nomega-methylarginine, which are reversible inhibitors of nitric oxide
      synthase. A dimethylargininase has been isolated from bovine brain tissue and was
      characterized by using immunological, kinetic, and spectroscopic techniques.
      Western blot analysis using polyclonal antibodies revealed that the enzyme is
      widely distributed in bovine with the highest relative concentrations found in
      brain and kidney tissue. A similar tissue distribution has also been reported for
      the other so far isolated dimethylargininase from rat kidney [Ogawa, T., Kimoto,
      M., and Sasaoka, K. (1989) J. Biol. Chem. 264, 10205-10209]. The bovine enzyme is
      a monomeric, globular protein (molecular mass approximately 31.2 kDa) containing
      one tightly bound Zn2+ ion, which can be removed by dialysis against 1,10
      phenanthroline. The determination of kinetic constants for both the native (holo
      protein) and the zinc-depleted (apo-protein) enzyme at 37 degrees ?C established
      that the dimethylargininase is not a zinc hydrolase. The specific activity was
      0.66 unit/mg for the holo-protein and 0.19 unit/mg for the apo-protein. The
      secondary structure determination of the native enzyme by circular dichroism
      revealed 41% alpha-helix and 32% beta-sheet and beta-turn structure. In the apo
      enzyme, a small, but significant decrease in the alpha-helical content (5%) was
      observed, consistent with a marked decrease in enzymatic activity to 30%. Upon
      preincubation of both enzyme forms at 50 degrees C, only the holo-enzyme showed a
      residual enzymatic activity. In thermostability studies, a 7 degrees C lower
      apparent Tm value was observed for the apo-enzyme compared to the 66 degrees C
      for the holo-enzyme, suggesting that the zinc ion has a structure-stabilizing
      role. Besides the tightly bound zinc, additional Zn2+ ions inhibit the enzyme
      competitively with a Ki value of 2.0 microM. A possible interrelationship between
      dimethylargininase and nitric oxide synthase is discussed.

PMID- 9537996
TI  - Evidence for axial coordination of 5,6-dimethylbenzimidazole to the cobalt atom
      of adenosylcobalamin bound to diol dehydratase.
AB  - It was demonstrated by electron paramagnetic resonance (EPR) spectroscopy that
      organic radical intermediates disappeared and cob(II)alamin accumulated upon
      suicide inactivation of diol dehydratase by 2-methyl-1,2-propanediol. The
      resulting EPR spectra showed that the eight hyperfine lines due to the divalent
      cobalt atom of cob(II)alamin further split into triplets by the superhyperfine
      coupling to the 14N nucleus. Essentially the same superhyperfine splitting of the
      octet into triplets was observed with [14N]- and [15N]apoenzyme. When the
      adenosyl form of [14N2]- and [15N2]imidazolyl analogues of the coenzyme [Toraya,
      T., and Ishida, A. (1991) J. Biol. Chem. 266, 5430-5437] was used with unlabeled
      apoenzyme, the octet showed superhyperfine splitting into triplets and doublets,
      respectively. Therefore, it was concluded that cobalamin is bound to this enzyme
      with 5,6-dimethylbenzimidazole coordinating to the cobalt atom. This conclusion
      is consistent with the fact that the consensus sequence forming part of a
      cobalamin-binding motif, conserved in methionine synthase and some of the other
      cobalamin enzymes, was not found in the deduced amino acid sequences of the
      subunits of diol dehydratase. Adenosylcobinamide methyl phosphate, a coenzyme
      analogue lacking the nucleotide moiety, underwent cleavage of the cobalt-carbon
      bond upon binding to the enzyme in the presence of substrate, forming a
      cob(II)inamide derivative without nitrogenous base coordination, as judged by EPR
      and optical spectroscopy. Therefore, this analogue may be a useful probe for
      determining whether the replacement of the 5, 6-dimethylbenzimidazole ligand by a
      histidine residue takes place upon binding of cobalamin to proteins.

PMID- 9537997
TI  - Identification of a two EF-hand Ca2+ binding domain in lobster skeletal muscle
      ryanodine receptor/Ca2+ release channel.
AB  - The lobster skeletal muscle Ca2+ release channel, known also as the ryanodine
      receptor, is composed of four polypeptides of approximately 5000 amino acids
      each, like its mammalian counterparts. Clones encoding the carboxy-terminal
      region of the lobster ryanodine receptor were isolated from a lobster skeletal
      muscle cDNA library. Analysis of the deduced 1513 carboxy-terminal amino acid
      sequence suggests a cytoplasmic Ca2+ binding domain consisting of two EF-hand
      Ca2+ binding motifs (amino acid residues 594-656). The Ca2+ binding properties of
      this domain were assessed by preparing bacterial fusion proteins with sequences
      from the lobster Ca2+ binding domain and the corresponding sequences of the
      rabbit cardiac and skeletal muscle ryanodine receptors. The lobster skeletal
      muscle fusion protein bound 45Ca2+ in Ca2+ overlays, and bound two Ca2+ under
      equilibrium binding conditions with a Hill dissociation constant (KH) of 0.9 mM
      and coefficient (nH) of 1.4. Rabbit skeletal and cardiac fusion proteins bound
      two Ca2+ with KHs of 3.7 and 3.8 mM and nHs of 1.1 and 1.3, respectively. Similar
      to results previously reported for the mammalian RyRs, the lobster RyR was
      activated by micromolar Ca2+ and inhibited by millimolar Ca2+, as determined in
      single-channel and [3H]ryanodine binding measurements. These results suggest that
      the two EF-hand Ca2+ binding domain of the lobster Ca2+ release channel as well
      as the corresponding regions of the mammalian channels may play a role in Ca2+
      inactivation of sarcoplasmic reticulum Ca2+ release.

PMID- 9537998
TI  - Sst2 is a GTPase-activating protein for Gpa1: purification and characterization
      of a cognate RGS-Galpha protein pair in yeast.
AB  - Genetic studies in the yeast Saccharomyces cerevisiae have shown that SST2
      promotes pheromone desensitization in vivo. Sst2 is the founding member of the
      RGS (regulators of G protein signaling) family of proteins, which in mammals act
      as GAPs (GTPase activating proteins) for several subfamilies of Galpha proteins
      in vitro. A similar activity for Sst2 has not been demonstrated, and it is not
      self-evident from sequence homology arguments alone. Here we describe the
      purification of Sst2 and its cognate Galpha protein (Gpa1) in yeast, and
      demonstrate Sst2-stimulated Gpa1 GTPase activity. His-tagged versions of Sst2 and
      Gpa1 were expressed in E. coli, and purified using Ni2+-agarose and ion exchange
      chromatography. Time-course binding experiments reveal that Sst2 does not affect
      the binding or release of guanine nucleotides. Similarly, steady-state GTPase
      assays reveal that Sst2 does not alter the overall rate of hydrolysis, including
      the rate-limiting nucleotide exchange step. Single-turnover GTPase assays reveal,
      however, that Sst2 is a potent stimulator of GTP hydrolysis. Sst2 also exhibits
      GAP activity for mammalian Goalpha, and the mammalian RGS protein GAIP exhibits
      GAP activity for Gpa1. Finally, we show that Sst2 binds with highest affinity to
      the transition state of Gpa1 (GDP-AlF4--bound), and with much lower affinity to
      the inactive (GDP-bound) and active (GTPgammaS-bound) conformations. These
      experiments represent the first biochemical characterization of Gpa1 and Sst2,
      and provide a molecular basis for their well-established biological roles in
      signaling and desensitization.

PMID- 9537999
TI  - Characterization of the heparin-binding properties of human clusterin.
AB  - Clusterin is a highly conserved mammalian glycoprotein which has been predicted
      to contain heparin-binding sites. We tested this prediction by studying the
      interactions between heparin and clusterin using ELISA and heparin affinity
      chromatography methodologies. Two forms of biotinylated heparin were used in
      ELISA: heparin which had been directly biotinylated with a biotin-N
      hydroxysuccinimide ester and heparin which had been activated using
      epichlorohydrin and 1,6-diaminohexane prior to biotinylation. Both gave dose
      dependent increases in ELISA signal with increasing concentrations of
      biotinylated heparin, with the latter giving signals an order of magnitude
      greater than the former. There was a dose-dependent increase in the ELISA signal
      from bound biotinylated heparin with increasing concentrations of plate-bound
      clusterin. The apparent affinity constant for binding of biotinylated heparin to
      plate-bound clusterin at pH 6.0 was estimated as 0.06 +/- 0.02 microM. Unlabeled
      heparin blocked the binding of biotinylated heparin to clusterin over a
      concentration range similar to that of the binding of biotinylated heparin to
      plate-bound clusterin. The binding of biotinylated heparin to clusterin was
      independent of the presence or absence of Ca2+. The binding of biotinylated
      heparin to plate-bound clusterin increased with decreasing pH over the range 5.5
      8.0 and was characterized by an apparent pKa of 6.9. Clusterin in human serum
      bound to heparin-Sepharose at pH 6.0 but not at pH 7.4. Dot-blot experiments
      showed that one of the polypeptide chains of clusterin which had been reduced and
      alkylated under denaturing conditions bound to heparin-Sepharose. This chain was
      identified as the alpha chain from its N-terminal amino acid sequence.

PMID- 9538000
TI  - Solution structure of oxidized cytochrome c6 from the green alga Monoraphidium
      braunii.
AB  - Cytochrome c6 from Monoraphidium braunii, an 89-amino acid electron transfer
      protein, has been investigated by NMR in solution, in its oxidized form, at pH 7
      and 300 K. By using a combination of COSY, TOCSY, and NOESY experiments, 84% of
      the proton resonances have been assigned. A total of 1668 experimental NOE
      constraints, 1109 of which were meaningful, together with 288 pseudocontact
      shifts, have been used to determine the structure in solution. This is
      represented as a family of 40 structures which have been energy minimized. The
      rmsd values with respect to the mean structure are 0.57 +/- 0.08 and 0.94 +/-
      0.09 A for the backbone and heavy atoms, respectively. The structure has been
      found to be very similar to that of the reduced form, except for a rearrangement
      in propionate 7, a feature which has been observed in all c-type cytochromes
      investigated so far. Such a feature could be relevant for the efficiency of the
      electron transfer pathway with either the oxidizing or the reducing partners.
      Other differences in the oxidation states have been noted in the region proposed
      to be involved in the interaction with the physiological partners.

PMID- 9538001
TI  - Mechanism of inducible nitric oxide synthase inactivation by aminoguanidine and L
      N6-(1-iminoethyl)lysine.
AB  - The inducible nitric oxide synthase (iNOS) selective inhibitors aminoguanidine
      (AG) and N6-(1-iminoethyl)-L-lysine (NIL), under conditions that support
      catalytic turnover, inactivate the enzyme by altering in different ways the
      functionality of the active site. NIL inactivation of the iNOS primarily targets
      the heme residue at the active site, as evidenced by a time- and concentration
      dependent loss of heme fluorescence that accompanies the loss of NO-forming
      activity. The NIL-inactivated iNOS dimers that have lost their heme partially
      disassemble into monomers with no fluorometrically detectable heme. AG
      inactivation of the iNOS is not accompanied by heme destruction, as evidenced by
      retention of heme fluorescence and absorbance after complete loss of NO-forming
      activity. The AG-inactivated iNOS dimers do not disassemble into monomers as
      extensively as NIL-inactivated dimers. Incubation of the iNOS with 14C-labeled
      NIL results in no detectable protein-associated radioactivity in the NIL
      inactivated iNOS, suggesting that the primary mechanism of the iNOS inactivation
      by NIL is heme alteration and loss. In contrast, incubations of iNOS with 14C
      labeled AG result in the incorporation of radioactivity into both iNOS protein
      and low molecular weight structures that migrate by SDS-PAGE similarly to free
      heme. These observations suggest that AG inactivation proceeds through multiple
      pathways of covalent modification of the iNOS protein and the heme residue at the
      active site, but which sustain the integrity of the heme porphyrin ring.

PMID- 9538002
TI  - Two superhelix density-dependent DNA transitions detected by changes in DNA
      adsorption/desorption behavior.
AB  - The adsorption behavior of covalently closed circular plasmid DNA at the
      mercury/water interface was studied by means of AC impedance measurements. The
      dependence of the differential capacitance (C) of the electrode double layer on
      the potential (E) was measured in the presence of adsorbed DNA. It was found that
      the C-E curves of supercoiled DNA at native and highly negative superhelix
      densities (sigma), relaxed covalently closed circular DNA, and nicked DNA
      differed from each other. A detailed study of topoisomer distributions ranging
      from -sigma of 0 to 0.11 revealed two supercoiling-dependent transitions, at
      about -sigma = 0.04 (transition TI) and 0.07 (transition TII). Transition TI was
      detected by measuring the height of the adsorption/desorption peak 1 (at about 
      1.2 V against the saturated calomel electrode) and the decrease of capacitance
      (DeltaC) at -0.35 V. This transition may be due to a sudden change in the ability
      of the DNA to respond to the alternating voltage, probably caused by changes in
      the DNA tertiary and/or secondary structure. Transition TII was detected by
      measuring peak 3* (at about -1.3 V), which was absent in topoisomers with -sigma
      less than 0.05. This transition is due to changes in the DNA
      adsorption/desorption behavior related to increased accessibility of bases at
      elevated negative superhelix density. Opening of the duplex at highly negative
      superhelix density was also detected by the single-strand selective probe of DNA
      structure, osmium tetroxide, 2, 2'-bipyridine. Our results suggest that
      electrochemical techniques provide sensitive experimental analysis of changes in
      DNA structure.

PMID- 9538003
TI  - Deletion of amino acids Glu146-->Arg160 in human apolipoprotein A-I (ApoA
      ISeattle) alters lecithin:cholesterol acyltransferase activity and recruitment of
      cell phospholipid.
AB  - Human apolipoprotein A-I (apoA-I) has an important role in the efflux of
      cholesterol from peripheral cells, the first step in reverse cholesterol
      transport. Deletion of amino acids Glu146-->Arg160 in apoA-I (apoA-ISeattle)
      removes a large section of a lipid binding helix and is associated in vivo with
      an atherogenic lipoprotein profile characterized by a deficiency in high-density
      lipoproteins (HDL). In the present study, we asked whether apoA-ISeattle had
      normal ability to recruit lipids from cells and to form nascent high-density
      lipoprotein (HDL) particles and whether the altered secondary structure affected
      lecithin:cholesterol acyltransferase (LCAT) activity. Wild-type apoA-I and apoA
      ISeattle expressed in transfected Chinese hamster ovary cells formed nascent HDL
      particles with similar density distribution and protein-to-lipid ratio.
      Phospholipid subclass distribution of apoA-ISeattle nascent HDL demonstrated a
      significant increase in sphingomyelin and phosphatidylethanolamine compared to
      wild type. ApoA-ISeattle nascent HDL had a unique size distribution compared to
      wild-type nascent HDL; large (9-20 nm) particles predominated while there were
      virtually no small (7.5 nm) particles. LCAT reactivity was impaired by apoA
      ISeattle nascent HDL where cholesterol esterification was only half that of wild
      type complexes. The apoA-ISeattle conformation on nascent HDL was studied with a
      panel of monoclonal antibodies (Mabs) specific for apoA-I. Mabs that recognize
      the putative LCAT activation site, residues 95-122, had normal reactivity. As
      expected, the Mabs that recognized residues 141-164 were unreactive because of
      the 146-160 deletion; in addition, there was low reactivity with a Mab that
      recognizes residues 220-242. The data suggest that apoA-I residues 146-160 and/or
      220-242 partake in normal LCAT activation and that cooperative interactions
      between helices may be important for maximal cholesterol esterification.

PMID- 9538004
TI  - Rhodopsin arginine-135 mutants are phosphorylated by rhodopsin kinase and bind
      arrestin in the absence of 11-cis-retinal.
AB  - Arginine-135, located at the border between the third transmembrane domain and
      the second cytoplasmic loop of rhodopsin, is one of the most highly conserved
      amino acids in the family of G protein-coupled receptors. The effect of mutation
      at Arg-135 on the ability of rhodopsin to undergo desensitization was
      investigated. Four mutants, R135K, R135Q, R135A, and R135L, were examined for
      their ability to be phosphorylated by rhodopsin kinase, to bind arrestin, and to
      activate the rod cell G protein, transducin (Gt). All of the mutants were
      phosphorylated, bound arrestin, and were able to activate Gt when reconstituted
      with 11-cis-retinal. Surprisingly, several of the mutants could be phosphorylated
      by rhodopsin kinase and could bind arrestin in the absence of 11-cis-retinal but
      were not able to activate Gt. These observations represent the first
      demonstration of a mutant G protein-coupled receptor that assumes a conformation
      able to interact with its G protein-coupled receptor kinase and arrestin, but not
      with its G protein, in the absence of ligand.

PMID- 9538005
TI  - Cation-promoted association of Escherichia coli phosphocarrier protein IIAGlc
      with regulatory target protein glycerol kinase: substitutions of a Zinc(II)
      ligand and implications for inducer exclusion.
AB  - In Escherichia coli, inducer exclusion is one mechanism by which glucose prevents
      unnecessary expression of genes needed for metabolism of other sugars. The basis
      for this mechanism is binding of the unphosphorylated form of the glucose
      specific phosphocarrier protein of the phosphoenolpyruvate:glycose
      phosphotransferase system, IIAGlc (also known as IIIGlc), to a variety of target
      proteins to prevent uptake or synthesis of the inducer. One of these target
      proteins is glycerol kinase (EC 2.1.7.30, ATP:glycerol 3-phosphotransferase),
      which is inhibited by IIAGlc. Glycerol kinase is the only IIAGlc target protein
      for which the structure of the complex is known. Association of these two
      proteins forms an intermolecular binding site for Zn(II) with metal ligands
      contributed by each protein, and Zn(II) enhances IIAGlc inhibition [Feese, M.,
      Pettigrew, D. W., Meadow, N. D., Roseman, S., and Remington, S. J. (1994) Proc.
      Natl. Acad. Sci. U.S.A. 91, 3544-3548]. Here, we show that the Zn(II) enhancement
      can be described quantitatively by a model with binding of Zn(II) to the complex
      with an apparent dissociation constant of less than 1 microM at pH 7.0 and 25
      degreesC. Initial velocity studies show that IIAGlc is an uncompetitive inhibitor
      with respect to both substrates, and the mechanism of inhibition is not altered
      by Zn(II). The Zn(II)-liganding residue contributed by glycerol kinase (Glu478)
      is substituted by using site-directed mutagenesis to construct the enzymes E478C,
      E478D, E478H, and E478Q. The substitutions have only small effects on the
      inhibition by IIAGlc in the absence of Zn(II), the catalytic properties, or other
      allosteric regulation. However, all of the substitutions abolish the Zn(II)
      enhancement of IIAGlc inhibition, and the X-ray crystallographic structures of
      the complexes of IIAGlc with the E478C and E478H mutants show these substitutions
      abolish binding of Zn(II) to the intermolecular site. These results support the
      hypothesis that Zn(II) enhances the affinity for complex formation by binding at
      the intermolecular site, i.e., cation promoted association. The high affinity for
      Zn(II) binding to the complex and the ability of the other four amino acid
      residues to efficiently substitute for Glu478 in all functions except binding of
      Zn(II) suggest that cation promoted association of these two proteins may have a
      role in inducer exclusion in vivo.

PMID- 9538006
TI  - Structure-function studies of ligand-induced epidermal growth factor receptor
      dimerization.
AB  - We present a novel 96-well assay which we have applied to a structure-function
      study of epidermal growth factor receptor dimerization. The basis of the assay
      lies in the increased probability of EGFRs being captured as dimers by a bivalent
      antibody when they are immobilized in the presence of a cognate ligand. Once
      immobilized, the antibody acts as a tether, retaining the receptor in its dimeric
      state with a resultant 5-7-fold increase in binding of a radiolabeled ligand
      probe. When the assay was applied to members of the EGF ligand family, murine
      EGF, transforming growth factor alpha, and heparin-binding EGF-like growth factor
      were comparable with human EGF (EC50 = 2nM); betacellulin, which has a broader
      receptor specificity, was slightly less effective. In contrast, amphiregulin (AR1
      84), which has a truncated C-tail and lacks a conserved leucine residue, was
      ineffective unless used at >1 microM. We further probed the involvement of the C
      tail and the conserved leucine residue in receptor dimerization by comparing the
      activities of two genetically modified EGFs (the chimera mEGF/TGFalpha44-50 and
      the EGF point mutant L47A) and a C-terminally extended form of AR (AR1-90) with
      those of two other unrelated EGF mutants (I23T and L15A). The potency of these
      ligands was in the order EGF > I23T > mEGF/TGFalpha44-50 > L47A = L15A >> AR1-90
      > AR1-84. Although AR was much worse than predicted from its affinity, this
      defect could be partially rectified by co-localization of the immobilizing
      antibody with heparin. Thus, it seems likely that AR cannot dimerize the EGFR
      unless other accessory molecules are present to stabilize its functional
      association with the EGFR.

PMID- 9538007
TI  - Differential membrane-binding and activation mechanisms of protein kinase C-alpha
      and -epsilon.
AB  - To elucidate the mechanisms of membrane binding and activation of conventional
      and novel protein kinase C (PKC), we measured the interactions of rat PKC-alpha
      and -epsilon with phospholipid monolayers and vesicles of various compositions.
      Besides the established difference in calcium requirement, the two isoforms
      showed major differences in their membrane-binding and activation mechanisms. For
      PKC-alpha, diacylglycerol (DG) specifically enhanced the binding of PKC-alpha to
      phosphatidylserine (PS)-containing vesicles by 2 orders of magnitude, allowing
      PKC-alpha high specificity for PS. Also, PKC-alpha could penetrate into the
      phospholipid monolayer with a packing density comparable to that of the cell
      membrane only in the presence of Ca2+ and PS. When compared to PKC-alpha, PKC
      epsilon had lower binding affinity for PS-containing vesicles both in the
      presence and in the absence of DG. As a result, PKC-epsilon did not show
      pronounced specificity for PS. Also, PKC-epsilon showed reduced penetration into
      PS-containing monolayers, which was comparable to the Ca2+-independent
      penetration of PKC-alpha into the same monolayers. Taken together, these results
      suggest the following: (1) The role of Ca2+ in the membrane binding of PKC-alpha
      is to expose a specific PS-binding site. (2) Once bound to membrane surfaces, PS
      specifically induces the partial membrane penetration of PKC-alpha that allows
      its optimal interactions with DG, hence the enhanced membrane binding and
      activation. (3) PKC-epsilon, due to the lack of Ca2+ binding, cannot specifically
      interact with PS and DG, which implies the presence of other physiological
      activator(s) for this isoform.

PMID- 9538008
TI  - Regulation of phospholipase D2: selective inhibition of mammalian phospholipase D
      isoenzymes by alpha- and beta-synucleins.
AB  - Two widely expressed mammalian phosphatidylcholine (PC)-specific phospholipases D
      (PLD), PLD1 and PLD2, have been identified. Recombinantly expressed PLD2 has high
      basal activity and is insensitive to GTP-binding protein activators of PLD1
      [Colley, W. C., et al. (1997) Curr. Biol. 7, 191-201]. To investigate the
      regulation of PLD2 we isolated PLD2, from mouse brain by immunoaffinity
      chromatography. The native and recombinant proteins have indistinguishable
      properties: PLD2 is potently activated by phosphoinositides with a vicinal 4,5
      phosphate pair but is not stimulated by guanosine 5'-O-(3-thio triphosphate)
      activated ADP-ribosylation factor-1, Rho family GTP-binding proteins, or protein
      kinases C-alpha, or -beta1. We used recombinant PLD2 in a reconstitution assay to
      search for regulators in cell and tissue extracts. Bovine brain contains a heat
      stable protein factor that inhibits PLD2 activity in vitro. This factor was
      purified to homogeneity and identified as a mixture of alpha- and beta-synucleins
      by microsequencing and Western blotting. Recombinantly expressed alpha- and beta
      synucleins inhibit PLD2 activity in vitro (K0.5 10 nM). Inhibition is not
      overcome by the protein or lipid activators of PLD1. Synucleins have been
      implicated in Parkinson's and Alzheimer's diseases. Our findings suggest that
      inhibition of PLD2 may be a function of synucleins. Modulation of PLD2 activity
      by synucleins may play a role in some aspects of the pathophysiologies that
      characterize these neurodegenerative diseases.

PMID- 9538009
TI  - Proximity of helices VIII (Ala273) and IX (Met299) in the lactose permease of
      Escherichia coli.
AB  - Three double-Cys mutant pairs--Ala273-->Cys/Met299-->Cys, Thr266-->Cys/Ile303-
      >Cys, and Thr266-->Cys/Ser306-->Cys--were constructed in a functional lac
      permease construct devoid of Cys residues, and the excimer fluorescence or
      electron paramagnetic resonance (EPR) was studied with pyrene- or spin-labeled
      derivatives, respectively. After reconstitution into proteoliposomes, excimer
      fluorescence is observed with mutant Ala273-->Cys/Met299-->Cys, but not with the
      single-Cys mutants nor with mutants Thr266-->Cys/Ile303-->Cys or Thr266-
      >Cys/Ser306-->Cys. Furthermore, spin-spin interaction is also observed with
      mutant Ala273-->Cys/Met299-->Cys, but only after the permease is reconstituted
      into proteoliposomes. The results provide independent support for the conclusions
      that helix VIII is close to helix IX and that the transmembrane helices of the
      permease are more loosely packed in a detergent micelle as opposed to a
      phospholipid bilayer.

PMID- 9538010
TI  - Human low-molecular-weight salivary mucin expresses the sialyl lewisx determinant
      and has L-selectin ligand activity.
AB  - Previously we showed that the low-molecular-weight mucin (MG2, encoded by MUC7),
      a major component of human submandibular/sublingual saliva, is a bacterial
      receptor that coats the tooth surface. Here we tested the hypothesis that the
      structure of its carbohydrate residues contains important information about its
      function. Purified MG2 (Mr 120 000) was digested with trypsin, and the resulting
      Mr 90 000 fragment, which carried primarily O-linked oligosaccharides, was
      subjected to reductive beta-elimination. The released oligosaccharides were
      characterized by using nuclear magnetic resonance spectroscopy and mass
      spectrometry. Of the 41 different structures we detected, the most prominent
      included NeuAcalpha2-->3Galbeta1-->3GalNAc-ol (sialyl-T antigen), Galbeta1-
      >4(Fucalpha1-->3)GlcNAcbeta1-->6(Galbeta1 -->3)GalNAc-ol [type 2 core with Lewisx
      (Lex) determinant], and NeuAcalpha2-->3Galbeta1-->4(Fucalpha1-->3)GlcNAcbet a1-
      >6(Galbeta1--> 3) GalNAc-ol [type 2 core with sialyl Lex (sLex) determinant]. We
      also detected di-, tri-, and pentasaccharides with one sulfate group. Lex, sLex,
      and related sulfated structures are ligands for selectins, adhesion molecules
      that mediate leukocyte trafficking. Therefore, we investigated whether MG2 was a
      selectin ligand. In an enzyme-linked immunosorbent assay, L-selectin chimeras
      interacted with immobilized MG2 in a Ca2+-dependent manner. L-Selectin chimeras
      also bound to MG2 immobilized on nitrocellulose. Together, these results suggest
      that the saccharides that MG2 carries could specify some of its important
      functions, which may include mediating leukocyte interactions in the oral cavity.

PMID- 9538011
TI  - Spontaneous priming of a downstream module in 6-deoxyerythronolide B synthase
      leads to polyketide biosynthesis.
AB  - Modular polyketide synthases such as 6-deoxyerythronolide B synthase (DEBS)
      catalyze the biosynthesis of structurally complex natural products by repetitive
      condensation of simple carboxylic acid monomers. The synthase can be divided into
      groups of domains, called "modules", each of which is responsible for one cycle
      of chain extension and processing. The modular nature of these enzymes suggests
      that the biosynthetic pathway might be rationally reprogrammed by manipulation of
      synthases at the domain level. Although, several examples of successful
      engineering of DEBS have been reported, a critical issue which has not been well
      studied is the tolerance of "downstream" active sites to nonnatural substrates.
      Here, we report that the terminal modules of DEBS, which normally process highly
      functionalized intermediates, are competent to carry out their natural functions
      on smaller, more simple substrates. Expressed in the absence of other DEBS
      proteins, the DEBS3 protein, which normally carries out the final two extension
      cycles in the synthesis of 6-deoxyerythronolide B (6-dEB), is spontaneously
      primed with a C3 carboxylic acid. This substrate is then extended through two
      condensation cycles to form a triketide. Tolerance of the "shortened"
      intermediates in the biosynthesis of this triketide, in combination with results
      reported elsewhere [Jacobsen, J. R., Hutchinson, C. R., Cane, D. E., and Khosla,
      C. (1997) Science 277, 367-369], suggests that relaxed substrate specificity may
      be a common feature of modular polyketide synthases. Interestingly, priming of
      DEBS3 appears to proceed, not by acyltransfer from propionyl-CoA, but by
      decarboxylation of an enzyme-bound methylmalonyl extender unit. This is the
      second example of decarboxylative priming within DEBS [see also Pieper, R.,
      Gokhale, R. S., Luo, G., Cane, D. E., and Khosla, C. (1997) Biochemistry 36, 1846
      1851] and suggests that, in the absence of an acceptable primer (or transferred
      intermediate), decarboxylative priming of ketosynthase domains may be a general
      property of modular polyketide synthases.

PMID- 9538012
TI  - Mechanistic studies of the biosynthesis of paratose: purification and
      characterization of CDP-paratose synthase.
AB  - The 3,6-dideoxyhexoses can be found in the cell wall lipopolysaccharide of Gram
      negative bacteria, where they have been shown to be the dominant antigenic
      determinants. All naturally occurring 3,6-dideoxyhexoses, with colitose as the
      only exception, are biosynthesized via a complex pathway that begins with CDP-d
      glucose. Included in this pathway is CDP-paratose synthase, an essential enzyme
      in the formation of the 3,6-dideoxy sugars, CDP-paratose and CDP-tyvelose.
      Recently, the gene encoding CDP-paratose synthase in Salmonella typhi, rfbS, has
      been identified and sequenced [Verma, N., and Reeves, P. (1989) J. Bacteriol.
      171, 5694-5701]. On the basis of this information, we have amplified the rfbS
      gene by polymerase chain reaction (PCR) from S. typhi and cloned this gene into a
      pET-24(+) vector. Expression and purification of CDP-paratose synthase have
      allowed us to fully characterize the catalytic properties of this enzyme, which
      is a homodimeric protein with a preference for NADPH over NADH. It catalyzes the
      stereospecific hydride transfer of the pro-S hydrogen from the C-4' position of
      the reduced coenzyme to C-4 of the substrate, CDP-3,6-dideoxy-D-glycero-D-glycero
      4-hexulose. The overall equilibrium of this catalysis greatly favors the
      formation of the reduced sugar product and the oxidized coenzyme. Interestingly,
      this enzyme also exhibits a high affinity for NADPH with a much smaller
      dissociation constant (Kia) of 0.005 +/- 0.002 microM compared to the Km of 26 +/
      8 microM for NADPH. While this unusual property complicated the interpretation
      of the kinetic data, the kinetic mechanism of CDP-paratose synthase as explored
      by the combination of bisubstrate kinetic analysis, product inhibition studies,
      and dead-end competitive inhibition studies is most consistent with a Theorell
      Chance mechanism. The present study on CDP-paratose synthase, a likely new member
      of the short-chain dehydrogenase family, represents the first detailed
      characterization of this type of ketohexose reductase, many of which may share
      similar properties with CDP-paratose synthase.

PMID- 9538013
TI  - Identification of the quinone cofactor in mammalian semicarbazide-sensitive amine
      oxidase.
AB  - Mammalian semicarbazide-sensitive amine oxidase (SSAO) enzymes have been
      classified as EC 1.4.3.6 [amine:oxygen oxidoreductase (deaminating)(copper
      containing)]. However, both the identity of the quinone cofactor and the presence
      of copper remain unconfirmed, and SSAO has proved impossible to purify to
      homogeneity in sufficient yield to permit cofactor identification. To circumvent
      this problem, we have partially purified SSAO enzymes from bovine and porcine
      aortae and have established, with a redox-cycling assay, that no other
      quinoproteins were present in enzyme preparations. Enzymes were then derivatized
      with (p-nitrophenyl)hydrazine (p-NPH), which forms a covalent yellow complex with
      the quinone cofactor. Visible absorbance spectra of derivatized bovine and
      porcine enzymes (respective lambdamax values 456 and 476 nm at neutral pH,
      shifting to 580 and 584 nm in 2 M KOH) were consistent with the presence of
      (2,4,5-trihydroxyphenyl)alanine quinone (TPQ) as cofactor. Resonance Raman
      spectra were essentially identical to that for pea seedling amine oxidase, a
      known TPQ-containing enzyme. Extensive digestion of SSAO enzymes, and of porcine
      kidney diamine oxidase, with pronase E yielded species with identical
      chromophoric properties characteristic of the dipeptide, TPQ(p-NPH)-Asp.
      Thermolytic digestion of porcine SSAO gave two cofactor-containing peptides that
      contained a TPQ consensus sequence, Asn-X-Asp-Tyr-Tyr, where X is a blank cycle
      corresponding to TPQ. N-terminal sequencing of whole enzymes revealed a membrane
      spanning region typical of an extracellular type II glycoprotein. These results
      confirm the presence of TPQ in mammalian membrane-bound SSAO ectoenzymes.

PMID- 9538014
TI  - Crystallographic study of steps along the reaction pathway of D-amino acid
      aminotransferase.
AB  - The three-dimensional structures of two forms of the D-amino acid
      aminotransferase (D-aAT) from Bacillus sp. YM-1 have been determined
      crystallographically: the pyridoxal phosphate (PLP) form and a complex with the
      reduced analogue of the external aldimine, N-(5'-phosphopyridoxyl)-d-alanine
      (PPDA). Together with the previously reported pyridoxamine phosphate form of the
      enzyme [Sugio et al. (1995) Biochemistry 34, 9661], these structures allow us to
      describe the pathway of the enzymatic reaction in structural terms. A major
      determinant of the enzyme's stereospecificity for D-amino acids is a group of
      three residues (Tyr30, Arg98, and His100, with the latter two contributed by the
      neighboring subunit) forming four hydrogen bonds to the substrate alpha-carboxyl
      group. The replacement by hydrophobic groups of the homologous residues of the
      branched chain L-amino acid aminotransferase (which has a similar fold) could
      explain its opposite stereospecificity. As in L-aspartate aminotransferase (L
      AspAT), the cofactor in D-aAT tilts (around its phosphate group and N1 as pivots)
      away from the catalytic lysine 145 and the protein face in the course of the
      reaction. Unlike L-AspAT, D-aAT shows no other significant conformational changes
      during the reaction.

PMID- 9538015
TI  - Characterization of hydrogen bonding in the complex of adenosine deaminase with a
      transition state analogue: a Raman spectroscopic study.
AB  - The Raman spectra of purine ribonucleoside as well as a stable model compound (1
      methoxyl-1,6-dihydropurine ribonucleoside), free in solution and bound into its
      complex with adenosine deaminase (ADA), have been studied by Raman difference
      spectroscopy. Using purine riboside analogues labeled with 15N1 or 13C6 and the
      theoretical frequency normal-mode analyses of these molecules using ab initio
      quantum mechanic methods, we have positively identified many of the Raman bands
      in the enzyme-bound inhibitor. The spectrum of the enzyme-bound inhibitor is
      consistent with the enzyme-catalyzed hydration of the purine base to yield 1
      hydroxyl-1,6-dihydropurine ribonucleoside, as suggested earlier by X-ray
      crystallographic studies. In addition, the Raman data and subsequent vibrational
      analyses show that the binding-induced Raman spectral changes of the inhibitor
      can be modeled by the formation of a strong hydrogen bond to its N1-H bond. This
      hydrogen bond, apparently between the N1-H of the inhibitor and the Odelta1 of
      Glu217 in ADA, causes a substantial N1-H bending frequency increase of about 50
      100 cm-1 compared to its solution value, and this results in an estimated
      enthalpy of the hydrogen bond of 4-10 kcal/mol. The relationship of transition
      state stabilization in the catalytic strategy of this efficient enzyme to such a
      bonding pattern is discussed.

PMID- 9538016
TI  - The MotA transcriptional activator of bacteriophage T4 binds to its specific DNA
      site as a monomer.
AB  - During bacteriophage T4 middle mode gene expression, the MotA transcription
      factor binds to T4 middle promoters at a -30 mot box consensus sequence to allow
      activation. Previous binding studies showed that MotA forms multiple gel-shifted
      complexes with DNA, and structural evidence suggested that MotA dimerizes upon
      DNA binding. We have shown that a short (13 bp) mot box DNA substrate binds MotA
      protein but fails to form slower migrating complexes. Therefore, the slower
      migrating complexes in gel shift assays are caused by DNA-mediated binding
      events. Competition experiments indicate that the slower migrating complexes are
      formed by nonspecific binding events, while the first-shifted complex is caused
      by specific binding to the mot box. Saturation binding experiments revealed that
      the stoichiometry of MotA binding to DNA is 1:1 in the first-shifted complex,
      while the slower complexes apparently contain MotA multimers. Gel shift assays
      using mixtures of MotA and a GST-MotA fusion protein supported the conclusion
      that the first-shifted complex contains one protein molecule bound to DNA.
      Furthermore, MotA monomers were cross-linked by glutaraldehyde under conditions
      where slower complexes exist, but not under conditions that lead to only the
      first-shifted complex. We conclude that MotA binds specifically to the mot box as
      a monomer and that additional nonspecific binding events require flanking DNA.

PMID- 9538017
TI  - The binding site of a specific aminoglycoside binding RNA molecule.
AB  - A small (40 nucleotides) stem-loop derivative (J6f1) of a specific aminoglycoside
      binding RNA aptamer, containing a 3 nt and a 1 nt bulge, has previously been
      shown to stoichiometrically bind tobramycin with a dissociation constant of
      approximately 5 nM [Hamasaki, K., Killian, J., Cho, J. and Rando, R. R. (1997)
      Biochemistry 36, 1367-1371]. This construct can strongly discriminate among
      similar aminoglycosides with respect to binding. A combination of chemical
      interference studies, chemical modification studies, and mutational studies are
      performed to define the aminoglycoside binding site of J6f1. Recognition of the
      aminoglycoside by J6f1 involves contacts with nucleotide bases, rather than with
      the phosphate backbone. The binding site 1 comprised of part of the stem-loop
      region. The two bulges are also essential for high affinity and stoichiometric
      binding of tobramycin. These bulges are probably important for prying open the
      double helical region, thereby allowing the aminoglycoside access to the
      nucleotide bases.

PMID- 9538018
TI  - Sequence dependence and characteristics of bends induced by site-specific
      polynuclear aromatic carcinogen-deoxyguanosine lesions in oligonucleotides.
AB  - The tumorigenic metabolite of benzo[a]pyrene, the (+)-7R,8S,9S,10R enantiomer,
      and the nontumorigenic mirror-image isomer, (-)-7S,8R,9R, 10S, of r7,t8-dihydroxy
      t9,10-epoxy-7,8,9, 10-tetrahydrobenzo[a]pyrene (anti-BPDE) bind covalently to the
      exocyclic amino group of deoxyguanosine (N2-dG) in native DNA. These adducts can
      cause structural perturbations such as DNA bends, which in turn may influence the
      cellular processing of these lesions. The characteristics of bends in site
      specifically modified oligodeoxyribonucleotide duplexes induced by single (+)-
      and (-)-anti-[BP]-N2-dG lesions were examined by self-ligation and gel
      electrophoresis techniques. The modified residues (dG*) were centrally positioned
      in the 11-mer oligonucleotide d(CACAXG*XACAC) complexed with the natural
      complementary strands, with X = T or C, or in oligonucleotides 16 or 22 base
      pairs long with the same centrally positioned 11-mer. Among the four
      stereochemically distinct lesions, the 10S(+)-trans-anti-[BP]-N2-dG adducts were
      significantly more bent than any of the other three stereoisomeric adducts and
      were selected for detailed studies. In the TG*T sequence context (X = T), the
      retardation factor RL (apparent length of multimer/sequence length) is
      approximately independent of the phasing (distance, in base pairs, between the
      lesions) of the adducts with respect to the helical repeat (10.5 base pairs/helix
      turn). In contrast, in the CG*C sequence context (X = C), RL is markedly lower in
      the case of ligated 16-mers than in the case of ligated 11-mer duplexes. The
      dependence of RL on the phasing of the bends as a function of the helical repeat,
      indicate that the bends associated with (+)-trans-anti-[BP]-N2-dG lesions are
      relatively rigid in the d(...CG*C...).d(...GCG...) sequences, and flexible in the
      d(...TG*T...).d(...ACA...) sequence context. These differences are attributed to
      the orientations of the pyrenyl residues on the 5'-side of the modified
      deoxyguanosine residues in the minor groove and to the intrinsic roll and tilt
      characteristics of DNA dinucleotide steps CG, GC, TG, and GT. The influence of
      flanking bases on the extent and character of DNA bending suggest that base
      sequence effects may be important in the cellular processing of (+)-trans-anti
      [BP]-N2-dG lesions.

PMID- 9538019
TI  - Bacteriorhodopsin's intramolecular proton-release pathway consists of a hydrogen
      bonded network.
AB  - In its proton-pumping photocycle, bacteriorhodopsin releases a proton to the
      extracellular surface at pH 7 in the transition from intermediate L to
      intermediate M. The proton-release group, named XH, was assigned in low
      temperature FT-IR studies to a single residue, E204 [Brown, L. S., Sasaki, J.,
      Kandori, H., Maeda, A., Needleman, R. , and Lanyi, J. K. (1995) J. Biol. Chem.
      270, 27122-27126]. The time-resolved room-temperature step-scan FT-IR photocycle
      studies on wild-type and E204Q-, and E204D-mutated bacteriorhodopsin, which we
      present here, show in contrast that the FT-IR data give no evidence for
      deprotonation of E204 in the L-to-M transition. Therefore, it is unlikely that
      E204 represents XH. On the other hand, IR continuum absorbance changes indicate
      intramolecular proton transfer via an H-bonded network to the surface of the
      protein. It appears that this H-bonded network is spanned between the Schiff base
      and the protein surface. The network consists at least partly of internally bound
      water molecules and is stabilized by E204 and R82. Other not yet identified
      groups may also contribute. At pH 5, the intramolecular proton transfer to the
      surface of the protein seems not to be disturbed. The proton seems to be buffered
      at the surface and later in the photocycle released into the bulk during BR
      recovery. Intramolecular proton transfer via a complex H-bonded network is
      proposed to be a general feature of proton transfer in proteins.

PMID- 9538020
TI  - Human P-glycoprotein exhibits reduced affinity for substrates during a catalytic
      transition state.
AB  - Human P-glycoprotein (Pgp), a plasma membrane protein that confers multidrug
      resistance, functions as an ATP-dependent drug efflux pump. Pgp contains two ATP
      binding/utilization sites and exhibits ATPase activity that is stimulated in the
      presence of substrates and modulating agents. The mechanism of coupling of ATP
      hydrolysis to drug transport is not known. To understand the role of ATP
      hydrolysis in drug binding, it is necessary to develop methods for purifying and
      reconstituting Pgp that retains properties including stimulation of ATPase
      activity by known substrates to an extent similar to that in the native membrane.
      In this study, (His)6-tagged Pgp was expressed in Trichoplusia ni (High Five)
      cells using the recombinant baculovirus system and purified by metal affinity
      chromatography. Upon reconstitution into phospholipid vesicles, purified Pgp
      exhibited specific binding to analogues of substrates and ATP in affinity
      labeling experiments and displayed a high level of drug-stimulated ATPase
      activity (specific activity ranging from 4.5 to 6.5 micromol min-1 mg-1). The
      ATPase activity was inhibited by ADP in a competitive manner, and by vanadate and
      N-ethylmaleimide at low concentrations. Vanadate which is known to inhibit ATPase
      activity by trapping MgADP at the catalytic site inhibited photoaffinity labeling
      of Pgp with substrate analogues, [125I]iodoarylazidoprazosin and [3H]azidopine,
      only under ATP hydrolysis conditions. Because vanadate-trapped Pgp is known to
      resemble the ADP and phosphate-bound catalytic transition state, our findings
      indicate that ATP hydrolysis results in a conformation with reduced affinity for
      substrates. A catalytic transition conformation with reduced affinity would
      essentially result in substrate dissociation and supports a model for drug
      transport in which an ATP hydrolysis-induced conformational change leads to drug
      release toward the extracellular medium.

PMID- 9538021
TI  - Catalysis by phospholipase C delta1 requires that Ca2+ bind to the catalytic
      domain, but not the C2 domain.
AB  - The hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) by
      phosphoinositide-specific phospholipase C (PLC) is absolutely dependent on Ca2+.
      The PH domain truncated catalytic core of rat phospholipase C delta1 (PLC-delta1)
      has Ca2+ binding sites in its catalytic and C2 domains, and potential Ca2+
      binding sites in two EF-hands. A catalytically inactive PLC-delta1 catalytic core
      bound with low affinity to PIP2-containing vesicles in the presence of Ca2+. A
      mutant PLC-delta1 has been engineered which lacks the C2 domain Ca2+ binding site
      and the surrounding loops known as the jaws. Isothermal calorimetric titration
      showed four Ca2+ ions bind to the wild-type PLC-delta1 catalytic core in solution
      but only one binds to the C2 domain jaws deletion mutant. The activity and Ca2+
      dependence of wild-type and mutant phospholipase Cs were determined using
      substrate incorporated in detergent micelles and in large unilamellar vesicles.
      The activities of wild-type and mutant were identical to each other in both assay
      systems. Wild-type and the C2 jaws deletion mutant of PLC have Hill coefficients
      of 1.12-1.16 with respect to [Ca2+]. We conclude that a single Ca2+ bound to the
      catalytic domain is entirely responsible for the Ca2+ dependence of the basal
      activity of PLC-delta1.

PMID- 9538023
TI  - Parasitism by a protozoan in the hemolymph of the giant clam, Tridacna crocea.
AB  - A parasitism by a protozoan was found in the giant clam, Tridacna crocea. The
      parasites were spindle-shaped, 8.6 +/- 0.5 micro m in length and 2.5 +/- 0.3
      micro m in width. Structural features of the apical complex of the parasite and a
      molecular phylogenetic analysis of its 18S rRNA gene sequence indicate that the
      protozoan belongs to the Apicomplexa. No flagellum was observed in the parasitic
      protozoan. It infected the eosinophilic granular hemocyte, one of the three types
      of hemocytes in the clam hemolymph, but it is not known whether it influenced the
      growth of the clam.

PMID- 9538022
TI  - Structure/function analyses of recombinant variants of human factor Xa: factor Xa
      incorporation into prothrombinase on the thrombin-activated platelet surface is
      not mimicked by synthetic phospholipid vesicles.
AB  - This report describes the expression, purification, and characterization of a
      series of recombinant factor Xa variants bearing aspartate substitutions for each
      of the glutamate residues which normally undergo gamma-carboxylation. Factor X
      was expressed in human embryonic kidney cells and purified from conditioned media
      by immunoaffinity and hydroxylapatite chromatography. Factor X was activated with
      Russell's viper venom factor X activator, and single-chain unactivated factor X
      was removed from activated factor X by size-exclusion chromatography. Recombinant
      wild-type factor Xa had normal activity in a clotting assay, and mutants with
      aspartate substitutions for glas residues 16, 26, and 29 had no detectable
      clotting activity. In purified component assays, these gla variants had
      essentially no detectable activity in the prothrombinase complex assembled on
      synthetic phospholipid vesicles but had significant activity when the
      prothrombinase was assembled on thrombin-activated platelets. In addition, the
      gla 32 variant had normal activity in the platelet prothrombinase but diminished
      activity in prothrombinase assembled on synthetic PSPC vesicles. These
      differences were not accounted for by the total phospholipid composition of the
      thrombin-activated platelet membrane. We have produced fully active recombinant
      human factor Xa and demonstrated that gla residues 16, 26, and 29 are critical
      for normal activity of factor Xa. More importantly, this study provides an
      extensive characterization of macromolecular enzyme complex formation with gla
      variants of a vitamin K-dependent coagulation protein and provides evidence that
      prothrombinase complex assembly on thrombin-activated platelets is not equivalent
      to assembly on synthetic phospholipid vesicles. The data suggest that thrombin
      activated platelets possess some element(s) (other than 30% phosphatidyl serine
      or factor Va), presumably either protein or phospholipid, that serves as a
      component of the factor Xa binding site.

PMID- 9538024
TI  - Phylogeny of amblyospora (Microsporida: amblyosporidae) and related genera based
      on small subunit ribosomal DNA data: A possible example of host parasite
      cospeciation.
AB  - Small subunit ribosomal RNA (SSU rRNA) gene sequences were analyzed for six
      species and four genera of microsporidia from mosquito hosts; Amblyospora stimuli
      (Aedes stimulans), Amblyospora californica (Culex tarsalis), Amblyospora sp.
      (Culex salinarius), Edhazardia aedis (Aedes aegypti), Culicosporella lunata
      (Culex pilosus), and Parathelohania anophelis (Anopheles quadrimaculatus).
      Comparison of these sequences to those of other microsporidia show that these
      sequences are longer with the SSU rRNA gene of E. aedis being the longest
      microsporidia sequenced to date (1447 base pairs). Parsimony, maximum likelihood,
      and distance methods produced identical trees, suggesting that the above
      microsporidian taxa, contrary to current classification schemes, form a
      monophyletic group. Relationships within this group are further supported by high
      bootstrap and decay analysis values. Based on the molecular analysis, P.
      anophelis is the most divergent species in this group of mosquito parasites.
      Amblyospora is paraphyletic with A. californica and Amblyospora sp., forming a
      sister taxon to a clade composed of E. aedis and A. stimuli. Culicosporella
      lunata comprises a sister taxon to the Amblyospora/Edhazardia clade. The pattern
      of host relationships on the tree provides preliminary evidence that the
      branching pattern seen here may indicate that host-parasite cospeciation is an
      important mechanism of evolution in this group.

PMID- 9538025
TI  - Physiological host specificity of microsporidia as an indicator of ecological
      host specificity.
AB  - For most groups of biological control agents the relationship between laboratory
      (physiological) host range and the host range in the field (ecological host
      range) has not been explored empirically. The objective of our study was to
      investigate this relationship using the North America gypsy moth, Lymantria
      dispar, as a model nontarget host for microsporidia from native North American
      Lepidoptera. The gypsy moth, L. dispar, a native of Europe, has been established
      in North America for nearly 130 years and presumably exposed to many species of
      microsporidia from sympatric native Lepidoptera. Nevertheless, microsporidia have
      never been observed in North American populations of L. dispar. We conducted
      traditional laboratory feeding experiments using microsporidia from 20
      lepidopteran host species and 1 coleopteran host species against L. dispar.
      Microsporidia from 18 native hosts infected L. dispar larvae. Although some of
      the infections were not typical of infections in the indigenous natural hosts,
      mature spores were produced in most of these infections. Horizontal transmission
      experiments, based on exposure of uninfected L. dispar larvae to infected L.
      dispar larvae, demonstrated that the microsporidia were far more host specific
      than the direct feeding experiments suggested. Of the three microsporidian
      biotypes that were horizontally transmitted between the nontarget L. dispar
      larvae, all were transmitted at very low levels. The results of our experiments
      provide additional evidence that the ecological host specificity of terrestrial
      microsporidia is much narrower than the physiological host specificity. Our
      studies establish the validity of using nonindigenous insect species with long
      term data sets on natural enemies associated with them as a tool for testing
      hypotheses about host specificity.

PMID- 9538026
TI  - Pathogenicity of the entomopathogenic fungi paecilomyces spp. and Beauveria
      bassiana against the silverleaf whitefly, Bemisia argentifolii.
AB  - Pathogenicities of three species of entomopathogenic fungi against preimaginal
      Bemisia argentifolii were measured and compared. Third-instar nymphs on excised
      leaves of Hibiscus rosa-sinensis were exposed to spray applications of 14
      isolates of Beauveria bassiana, 22 isolates of Paecilomyces fumosoroseus, and
      five isolates of Paecilomyces farinosus. B. bassiana and P. fumosoroseus isolates
      of diverse origins were highly pathogenic to the whitefly nymphs; median lethal
      doses of 14 of the 22 P. fumosoroseus and four of the 13 B. bassiana isolates
      ranged between 50 and 150 conidia/mm2. Five isolates of P. farinosus were also
      pathogenic; however, LC50s were relatively high, ranging between 350 and 4000
      conidia/mm2. Nymphs infected with all but one isolate of B. bassiana displayed a
      pronounced red pigmentation. Postmortem hyphal growth and sporulation of B.
      bassiana was relatively slow and usually confined to the region immediately
      surrounding the dead host. Whitefly nymphs patently infected with P. fumosoroseus
      and P. farinosus were lightly pigmented yellow or orange. Postmortem hyphal
      growth and sporulation of P. fumosoroseus rapidly covered the dead host and
      extended several millimeters onto the surrounding leaf surface. The results
      indicate that highly virulent strains of P. fumosoroseus and B. bassiana with
      considerable whitefly control potential are widespread and numerous.

PMID- 9538028
TI  - Implications of predator foraging on aphid pathogen dynamics.
AB  - The foraging behavior of starved and nonstarved second and fourth instar
      Coccinella septempunctata larvae on dead Acyrthosiphon pisum aphids, either
      infected with the entomopathogenic fungus Erynia neoaphidis (sporulating) or
      uninfected, was examined. Larvae searched for longer and fed less when presented
      with infected rather than uninfected A. pisum. Although no sporulating infected
      aphids were completely consumed, both adult and larval ladybirds can still be
      considered as intraguild predators. In a further study, fourth instar larvae fed
      on dying infected, dead infected (not sporulating), and dead uninfected aphids
      for similar periods of time but again the infected aphids were seldom entirely
      consumed. Live uninfected aphids were fed upon for significantly longer than any
      other prey. Infected aphids which were damaged at an early stage of infection (0,
      1, or 2 days after inoculation) did not sporulate, whereas damaged moribund
      aphids (3 days after inoculation) did subsequently sporulate. Damaged sporulating
      cadavers continued to sporulate. However, damage to moribund and sporulating
      infected aphids, both mechanical or due to C. septempunctata feeding, reduced the
      number of conidia subsequently produced. Larval feeding caused the most
      significant reduction. Under laboratory conditions, C. septempunctata foraging on
      infected aphids did, therefore, reduce the pathogen density. However, conidia
      produced from a damaged cadaver resulted in levels of transmission to healthy
      aphids comparable to that resulting from an intact cadaver. Furthermore, the
      presence of a foraging adult ladybird resulted in a significant increase in
      transmission of the fungus to healthy aphids. Preliminary studies to assess the
      potential of other aphid natural enemies as intraguild predators illustrated that
      adults of the generalist carabid, Pterostichus madidus, entirely consumed
      sporulating cadavers. Third instar lacewing, Chrysoperla carnea, and hoverfly,
      Episyrphus balteatus, larvae never fed on sporulating cadavers. The ecological
      implications of these results are discussed.

PMID- 9538027
TI  - Characterization of a granulosis virus from the castor semilooper, Achaea janata
      L.
AB  - The granulosis virus isolated from Achaea janata is composed of capsules (463 +/-
      25 x 280 +/- 22 nm) which contain single virus particles. The virus particles
      (274 +/- 9 x 95 +/- 4 nm) contain nucleocapsids (297 +/- 7 x 52 +/- 2 nm) within
      an envelope. The empty capsids measured 265 +/- 9 x 63 +/- 3 nm. SDS-PAGE
      electrophoresis was carried out and the granulin polypeptide (28.9 +/- 0.5 kDa)
      was found to contain two other associated polypeptides of molecular weight 58.2
      +/- 2.3 and 55.2 +/- 1.3 kDa, respectively. Protein gel electrophoresis of
      granulin gave degradation products from 27.2 to 15.4 kDa, when protease
      associated with capsules was not inhibited. The virus particles were found to
      contain 16 polypeptides with molecular weights ranging from 106.4 +/- 2.1 to 15.
      5 +/- 0.8 kDa and 12 of these polypeptides were contained in the nucleocapsids.
      The major polypeptide of the capsids had molecular weight of 34.9 +/- 0.3 kDa.
      Restriction profiles of viral DNA with seven enzymes were obtained and the
      average molecular weight was found to be approximately 92 +/- 7 kb. Southern
      hybridization of the restriction profiles of the viral DNA with SalI fragment
      from pUCTnGV (containing granulin gene) was performed and hybridization was found
      on single discrete fragments with molecular weights ranging from 12.0 to 2.7 kb.
      The GC content of AjGV DNA was found to be 65 +/- 1% and the genome size as
      determined from reassociation kinetics was 92 kb.

PMID- 9538029
TI  - The laboratory preference of annual legumes by pea weevil sitona lineatus L.
      (Col., curculionidae) and their effect on susceptibility of weevils to
      entomogenous nematodes.
AB  - The activity and natural mortality of Sitona lineatus weevils during the egg
      laying period may be connected with host plant preference. Preference of S.
      lineatus adults for early field pea and other pea cultivars influences their low
      feeding activity and results in lopff average body weight and higher
      susceptibility to entomogenous nematodes, Steinernema carpocapsae, S. feltiae,
      and Heterorhabditis bacteriophora.

PMID- 9538030
TI  - Field and laboratory studies of zebra mussel (Dreissena polymorpha) infection by
      the ciliate Conchophthirus acuminatus in the Republic of Belarus.
AB  - This study quantifies the infection prevalence and intensity of the European,
      commensal, host-specific ciliate Conchophthirus acuminatus (Scuticociliatida:
      Conchophthiridae) in five zebra mussel populations within the Republic of
      Belarus. Laboratory and field experiments were also conducted to assess variables
      affecting infection. C. acuminatus was found in zebra mussels in all five
      waterbodies sampled: Naroch, Myastro, and Lukomskoe Lakes, Skema Stream, and in
      the Svisloch River. Prevalence was always 100%, with the exception of shallow
      areas (</=0.5 m depth) in the Svisloch River. This was possibly the result of the
      elimination of the majority of infected zebra mussels each winter by a
      combination of factors, including ice scour, mallard duck predation, and
      fluctuating water levels. As a result, zebra mussels are not permanently present
      at shallow depths, and the mussels that we randomly sampled there during the
      summer were thus smaller (i.e., younger) and less infected than those present in
      deeper sections of the river. This is the first study to quantify the intensity
      of Conchophthirus infection in zebra mussels. When infection prevalence was 100%,
      it was not uncommon for zebra mussels to have 500-2,000 C. acuminatus in their
      mantle cavities, particularly those mussels ca. 15-30 mm in length. Zebra
      mussels, while relatively small bivalves, have one of the highest intensities
      ever reported for ciliates in the order Scuticociliatida. Infection intensity
      correlated directly with mussel length (range in r2 = 0.83-0.92). Transinfection
      of zebra mussels with C. acuminatus was achieved both in the laboratory and
      field, and represented the first successful trials to initiate protozoan
      infection in Dreissena. Laboratory experiments demonstrated that C. acuminatus
      rapidly leave their dying zebra mussel hosts, and this suggested that these
      mussels are likely a major source for the spread of C. acuminatus infection.
      Field trials indicated that the presence of mussels with high intensity
      infections can cause an increase in the levels of infection (both prevalence and
      intensity) in other zebra mussels in their microhabitat.

PMID- 9538031
TI  - Amblyospora salinaria n. sp. (Microsporidia: amblyosporidae), parasite of Culex
      salinarius (Diptera: culicidae): its life cycle stages in an intermediate host.
AB  - Horizontal transmission testing with an Amblyospora species from the mosquito
      Culex salinarius has documented the involvement of a copepod intermediate host.
      Meiospores (one type of uninucleate spore) of the Amblyospora sp. were infectious
      per os to female Macrocyclops albidus adults. All developmental stages in the
      copepod had unpaired nuclei (were haplophasic), starting with the sporoplasms
      from the meiospore, continuing as a succession of schizonts undergoing binary
      division and ending with sporulation, producing a second type of uninucleate
      spore. These spores, formed in the ovaries of M. albidus, were lanceolate,
      slightly curved and measured 13.23 x 3.85 microm. They infected C. salinarius
      larvae, both male and female, when ingested. In addition, cross-infectivity
      testing was conducted and demonstrated that while A. californica from C. tarsalis
      will infect C. salinarius, it does not complete its life cycle in this host.
      Based on these findings, we conclude that Amblyospora sp. from Culex salinarius
      is a distinct species and assign it the name Amblyospora salinaria n. sp.

PMID- 9538033
TI  - Screening mollusks for Wolbachia infection.
AB  - We screened 38 species of mollusks for infection by Wolbachia, a bacterium that
      is a common endosymbiont in arthropods, where it induces alterations in
      reproduction. Using a PCR assay, we could not detect the symbiont in any of the
      samples, indicating that, in mollusks, it might be absent.

PMID- 9538032
TI  - Environmental persistence of Bacillus thuringiensis spores following aerial
      application.
AB  - Soil and leaf populations of Bacillus thuringiensis (Bt) were monitored following
      aerial application of commercial Bt formulations at the rate of 72 billion
      international units per acre per year during a 5-year period. Data from soil
      sample spore counts suggested that Bt spores persisted in Wasatch forest soils
      for up to 2 years but they did not proliferate. Bt isolates were recovered from
      leaf samples 12 months post application from sprayed, previously sprayed and from
      nonsprayed areas. The frequency and diversity of Bt isolates recovered from
      leaves was independent of sample area spray history. In accordance with U.S.
      Forest Service criteria, aerial application of Bt during a 5-year period resulted
      in the eradication of gypsy moth (Lymantria dispar, L) from the Wasatch Front
      region of the Wasatch Mountain Range, Utah.

PMID- 9538034
TI  - Production of early expressed parasitism-specific proteins in alternate sphingid
      hosts of the braconid wasp Cotesia congregata.
AB  - Parasitism of Manduca sexta larvae by the braconid wasp Cotesia congregata or
      injection of C. congregata polydnavirus (CcPDV) causes numerous alterations in
      host physiology, including developmental arrest, abrogation of host immunity, and
      the production of three abundant early expressed proteins (EP1, EP2, and EP3)
      that are secreted in large amounts into the host's hemolymph. Here we compare the
      levels of these proteins present in the hemolymph of three other sphingid species
      that vary in their compatibility for C. congregata. Hyles lineata was found to be
      permissive for C. congregata and EP1, EP2, and EP3 were present in larval
      hemolymph at levels comparable to those found in hemolymph from parasitized M.
      sexta larvae. By contrast, the lowest levels of EP proteins were found in
      hemolymph from parasitized Pachysphinx occidentalis larvae and this species was
      found to be completely refractory, since C. congregata eggs were invariably
      encapsulated. Parasitism of Sphinx vashti by C. congregata resulted in moderate
      levels of EP production. While the observed immune response was incomplete and
      some encapsulation of C. congregata eggs and/or larvae was observed, low numbers
      of S. vashti nevertheless were able to complete their development and emerge as
      adults. Thus, a correlation was established between host compatibility and
      induction of synthesis of the three parasitism-specific proteins, although the
      linkage between quantitative levels of EP production and the extent of
      encapsulation was variable.

PMID- 9538035
TI  - Characterization of a nuclear polyhedrosis virus of Spodoptera frugiperda from
      Argentina.

PMID- 9538036
TI  - New isolate of Macosoma neustria nuclear polyhedrosis virus in Latvia.

PMID- 9538037
TI  - A rapid and specific method for the identification of Bacillus thuringiensis
      strains by indirect immunofluorescence.

PMID- 9538039
TI  - Exercise: Keep It Up. A Message from Preventive Medicine and Your Physician
AB  - Copyright

PMID- 9538038
TI  - Sex differences in susceptibility of house crickets, acheta domesticus, to
      experimental infection with Serratia liquefaciens.

PMID- 9538040
TI  - ACKNOWLEDGMENT

PMID- 9538041
TI  - ANNOUNCEMENTS

PMID- 9538042
TI  - Toxicity and carcinogenicity studies of oxazepam in the Fischer 344 rat.
AB  - Oxazepam and related benzodiazepines are used in the treatment of anxiety.
      Carcinogenicity studies of oxazepam were performed with the F344 rat because of
      marked differences in tumor responses observed in NTP studies with B6C3F1 and
      Swiss-Webster mice compared to the results of Sprague-Dawley rat studies
      submitted to the FDA by a manufacturer to support registration of the drug.
      Groups of 50 male and 50 female F344/N rats were fed diets containing 0, 625,
      2500, or 5000 ppm oxazepam for up to 105 weeks. A stop-exposure group of 50 males
      and 50 females received 10,000 ppm oxazepam in diet for 26 weeks, after which
      animals received control diet. All 5000- and 10, 000-ppm stop-exposure males died
      before the end of the study. Survival of 2500-ppm males and females was lower
      than that of controls. Body weight gains of 2500- and 5000-ppm males and females
      were less than those of controls. Male rats exposed to 2500 ppm had an increased
      incidence of renal tubule adenoma and hyperplasia. In addition, the incidences of
      renal tubule adenoma and hyperplasia were increased in the 10,000-ppm stop
      exposure group. The incidences of nephropathy in exposed females were greater
      than those in controls, and the severity of nephropathy increased in exposed
      males. Epithelial hyperplasia and chronic inflammation of the nonglandular
      stomach were increased in males given 2500 and 5000 ppm and the incidence of
      ulcers of the nonglandular stomach in 2500-ppm males was also greater than that
      in controls. In males exposed to 5000 ppm, mineralization of the glandular
      stomach and erosion of the duodenum were observed. In females exposed to 2500
      ppm, the incidences of epithelial hyperplasia, chronic inflammation, and ulcers
      of the nonglandular stomach and the incidence of erosion in the glandular stomach
      were increased. The incidences of centrilobular hepatocyte hypertrophy in males
      and females given 2500 and 5000 ppm were greater than those in controls. In
      summary, there was equivocal evidence of carcinogenicity in males based on
      increased renal tubule adenomas in groups which also had significantly enhanced
      nephropathy. There was no evidence of carcinogenicity of oxazepam in females
      given a diet containing 625, 2500, or 5000 ppm for 2 years or 10,000 ppm for 6
      months.

PMID- 9538043
TI  - Role of altered arachidonic acid metabolism in 2,3,7, 8-tetrachlorodibenzo-p
      dioxin-induced immune suppression in C57Bl/6 mice.
AB  - One of the most sensitive targets of 2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD)
      is the immune system. Many arachidonic acid (AA) metabolites are potent
      immunoregulatory molecules, and in other systems, TCDD has been shown to alter AA
      metabolism. Furthermore, the genes for cyclooxygenase (cox) contain a dioxin
      response element, suggesting that exposure to TCDD may directly alter cox levels
      and prostaglandin (PG)E2 production. To test the hypothesis that TCDD induces
      immune suppression by altering the production of immunomodulatory AA metabolites,
      we examined the effects of TCDD on splenic AA release, LTB4 and PGE2 production,
      and cox-1 and cox-2 expression. Exposure of C57Bl/6 mice to TCDD (15 microg/kg)
      resulted in a 2-fold increase in the release of AA from spleen cell membranes, a
      1.4-fold enhancement of LTB4 and PGE2 production in the spleen, and 3-fold higher
      PGE2 levels in the peritoneal cavity during the immune response to allogeneic
      P815 tumor cells. We examined the direct induction of cox-1 and cox-2 by TCDD and
      the indirect induction of cox-2 via TCDD-induced IL-1. Interestingly, exposure to
      TCDD did not alter message or protein levels of cox-1, cox-2, or IL-1 over the
      course of the response to P815. Various metabolic inhibitors were then used to
      address the in vivo role of TCDD-induced changes in AA metabolism. While these
      inhibitors blocked AA metabolism, they failed to affect the TCDD-induced
      suppression of either the cytotoxic T lymphocyte response to P815 tumor cells or
      antibody formation in response to sheep red blood cells. The lack of effect of
      TCDD on cox expression, combined with the failure of metabolic inhibitors to
      reverse the suppression caused by TCDD, supports the conclusion that TCDD
      immunotoxicity is likely not mediated by a direct effect on the production of
      immunomodulatory AA metabolites.

PMID- 9538044
TI  - Induction of oxidative stress in brain tissues of mice after subchronic exposure
      to 2,3,7,8-tetrachlorodibenzo-p-dioxin.
AB  - The ability of single doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) to
      induce oxidative stress in hepatic and some extrahepatic tissues of animals is
      well documented. However, no previous study has examined the ability of TCDD to
      induce oxidative stress and tissue damage in brain in vivo. In this study the
      ability of TCDD to induce oxidative stress in brain tissues of mice was studied
      after subchronic exposures. Groups of female B6C3F1 mice were treated orally with
      TCDD (0, 0.45, 1.5, 15, and 150 ng/kg/day) for 13 weeks, 5 days/week. The animals
      were euthanized 3 days after the last treatment and brain tissues were collected.
      Biomarkers of oxidative stress including production of superoxide anion, lipid
      peroxidation, and DNA-single-strand breaks (SSB) were determined. TCDD treatment
      resulted in significant and dose-dependent increases in the production of
      superoxide anion as assessed by reduction of cytochrome c. Significant increases
      were also observed in lipid peroxidation and DNA-SSB in those tissues, as
      assessed by the presence of thiobarbituric acid-reactive substances and the
      alkaline elution technique, respectively. These results clearly indicate that
      subchronic exposure to low doses of TCDD can induce oxidative tissue damage in
      brain tissues which may at least in part play a role in the effects of TCDD on
      the central nervous system.

PMID- 9538045
TI  - Trichloroethylene ototoxicity: evidence for a cochlear origin.
AB  - Trichloroethylene (TCE) is known to produce an unusual pattern of hearing
      impairment in laboratory animals marked by a preferential loss of threshold
      sensitivity at midfrequencies. The purpose of this research was to determine
      whether the TCE-induced auditory deficit results from cochlear dysfunction. Adult
      Long Evans hooded rats were exposed via inhalation to either 0 (clean air) or
      4000 ppm TCE (6 h/day for 5 days). Auditory thresholds for 1-40 kHz tones were
      determined 3 weeks after exposure using reflex modification audiometry (RMA; n =
      12/group). Cochlear electropotentials were measured during subsequent testing (n
      = 3-10/group) 5 to 7 weeks after exposure, including thresholds for cochlear
      action potentials (CAP) and the 1-microV cochlear microphonic for 2-40 kHz tones,
      and the N1 amplitude intensity function (40-90 dB SPL). Cochlear histopathology
      was assessed in midmodiolar preparations of a separate set of animals, exposed as
      before (n = 4/group). RMA testing confirmed a TCE-induced loss in midfrequency
      threshold sensitivity (8 and 16 kHz). CAP thresholds were elevated at
      midfrequencies (8 and 16 kHz) among TCE-treated subjects, along with a
      suppression of the N1 amplitude from 50 to 90 dB SPL. The cochlear microphonic, a
      nonpropagated ac potential generated largely by the outer hair cells, was not
      affected by the TCE treatment. Cochlear histopathology revealed a loss of spiral
      ganglion cells that was significant in the middle turn, but not in the basal
      turn. There was an inconsistent loss of hair cells among treated subjects. The
      data suggest strongly that the behaviorally determined loss in auditory function
      can be accounted for by a cochlear impairment and that the spiral ganglion cell
      may be a prominent target of TCE.

PMID- 9538046
TI  - Dose-response relationships between inhaled beryllium metal and lung toxicity in
      C3H mice.
AB  - Inhaled beryllium (Be) can induce a range of adverse pulmonary responses in
      animals and humans including acute pneumonitis, chronic granulomatous lung
      disease, and cancer. To facilitate comparisons with our previous data describing
      Be toxicity in rats, we evaluated the toxic effects of inhaled Be metal in mice.
      Groups of 34 strain C3H/HeJ mice were acutely exposed by the nose-only route to
      aerosolized Be metal to achieve measured initial lung burdens of 0, 1.7, 2.6, 12,
      or 34 microg. All mice received aerosolized 85 Sr-labeled fused aluminosilicate
      particles (85 Sr-FAPs) immediately before their Be exposure so that the influence
      of Be on lung retention of these poorly soluble tracer particles could be
      externally quantitated. Groups of mice were euthanized at 8, 15, 40, 90, 210, and
      350 days after exposure for evaluation of histopathological changes and for
      cytologic and biochemical indicators of lung damage measured in bronchoalveolar
      lavage fluid. Clearance of 85 Sr-FAP tracer particles through 196 days after
      exposure was delayed in mice receiving the 12 and 34 microg Be lung burdens, but
      not the 1.7 or 2.6 microg lung burdens. Increased total cell numbers, increased
      percentage of neutrophils, and elevated levels of total protein and the
      activities of beta-glucuronidase and lactate dehydrogenase in bronchoalveolar
      lavage fluid were observed in the two highest Be lung burden groups compared with
      controls. Lung lesions included particle-containing macrophages, granulomatous
      pneumonia, lymphocytic interstitial aggregates, and mononuclear interstitial
      infiltrates. These lesions were occasionally seen in mice receiving the 2.6
      microg lung burden, were present in most of the mice receiving 12 or 34 microg
      lung burdens, and were generally increased in severity with time and lung burden.
      Thus, we have demonstrated that a single, acute inhalation exposure to Be metal
      can chronically retard particle clearance and induce lung damage in mice. The
      initial lung burdens used caused responses ranging from no apparent effects to
      significant Be-induced responses. A comparison of these data with our previous
      data from rats indicates that the mass of Be metal required to induce lung damage
      in mice is similar to that needed for rats. When expressed on a lung weight
      normalized basis, mice appeared to be more resistant to the toxic effects of
      inhaled Be than rats.

PMID- 9538047
TI  - Subchronic toxicity of Di(2-ethylhexyl)phthalate in common marmosets: lack of
      hepatic peroxisome proliferation, testicular atrophy, or pancreatic acinar cell
      hyperplasia.
AB  - To evaluate the toxicological effect, di(2-ethylhexyl)phthalate (DEHP) was
      administered orally at 100, 500, and 2500 mg/kg to four male and four female
      marmosets in each group for 13 weeks. Its potentials of hepatic peroxisome
      proliferation, testicular atrophy, and pancreatic acinar cell hyperplasia were
      evaluated more closely. Clofibrate, which potently causes peroxisome
      proliferation in rodents, was administered in like manner at 250 mg/kg as a
      reference drug. DEHP induced significant suppression of weight gain in males at
      2500 mg/kg. However, the increase in liver mass and hypertrophy of hepatocytes
      were not detected in organ weight measurements or histopathological examination.
      The number of peroxisomes, volume density, peroxisome morphology, and peroxisomal
      enzyme activities were not different from those in the control group, though the
      males treated with 500 and 2500 mg/kg DEHP showed 1.3- and 1.4-fold increases in
      mean peroxisome volume, respectively. In contrast, clofibrate induced 2.2 (in
      male)- and 1.9-fold (in female) increases in hepatic cyanide-insensitive acyl CoA
      oxidation system activity, 1. 2 (in male)- and 1.7-fold (in female) increases in
      hepatic carnitine-dependent acetyltransferase activity, and 1.8 (in male)- and
      3.0-fold (in female) increases of carnitine-dependent palmitoyltransferase
      activity. Cytochrome P-450 contents tended to increase in all males and females
      administered 500 and 2500 mg/kg of DEHP and clofibrate associated with the
      increase in hepatic microsomal protein content, suggesting a relationship with
      the treatment. The atrophic change in the testis or proliferative change in the
      pancreatic acinar cells seen in rodents were not seen histopathologically; also,
      no changes were observed in testes weight, testicular zinc level, blood levels of
      testosterone and estradiol, pancreas weight, and blood levels of cholecystokinin.
      Finally, no changes considered to be due to the administration of DEHP were noted
      in blood chemical examination or pathological examination of other organs.

PMID- 9538048
TI  - Toxicity of subcutaneously administered recombinant human interleukin-2 in rats.
AB  - Recombinant human interleukin-2 (rIL-2) was administered subcutaneously to rats
      at doses of 0.3-10 mg/kg/day in a range-finding study and 0.03-0.3 mg/kg/day in a
      4-week toxicity study. Treatment-related effects were assessed by hematology,
      clinical chemistry, anti-rIL-2 antibody production, and gross and histopathologic
      evaluations. Doses of 1 mg/kg/day or above were not tolerated, resulting in death
      or moribund termination by Day 7. Slight decreases in red blood cell counts
      (including hematocrit and hemoglobin) were observed at >/= 0.1 mg/kg/day. White
      blood cells counts increased in a dose-dependent manner; increases were primarily
      due to increases in lymphocytes and eosinophils. Hepatic abnormalities, including
      increases in aspartate aminotransferase and bilirubin, were noted at 0.3
      mg/kg/day. Histologic findings were evident primarily in the spleen, liver, lung,
      and injection sites, with dose-related increases in inflammatory cell
      foci/infiltrates noted in these sites. Findings in the liver also included
      biliary hyperplasia, hepatocellular degeneration, necrosis, vascular mural
      thickening in the portal triads, and fibrosis. Red and white pulp hyperplasia and
      capsular fibrosis occurred in the spleen. Most clinical and histopathologic
      findings were reversible within 4 weeks after termination of treatment. Anti-rIL
      2 antibodies were detected beginning on Day 19 and were still present on Day 56.
      The pharmacological and toxicological effects associated with subcutaneous
      administration of rIL-2 are comparable to those reported after intravenous
      administration, indicating that subcutaneous dosing may be an alternative to the
      current clinical iv regimens.

PMID- 9538049
TI  - Phenylhydroxylamine: role in aniline-associated splenic oxidative stress and
      induction of subendocardial necrosis.
AB  - To elucidate the role of N-phenylhydroxylamine (PHA, N-hydroxylated metabolite of
      aniline) in the selective toxicity of aniline to the spleen, dose-dependent
      studies were conducted with PHA in rats. Male Sprague-Dawley rats were given four
      doses each (1 dose/day) of 0.025, 0.05, 0.1, or 0.2 mmol/kg PHA in 0.5 ml of
      aqueous agar (0.25%) by gavage. The control animals received an equal volume of
      vehicle only. The animals were euthanized 24 h following the last dose. PHA
      toxicity in the blood was evident from a dose-dependent increase of
      methemoglobin. The most affected organ was spleen, which appeared dark and
      enlarged (splenomegaly) and showed increased spleen-to-body weight ratios, which
      were 28, 40, 66, and 87% at PHA doses of 0.025, 0.05, 0.1, and 0.2 mmol/kg,
      respectively. Splenic lipid peroxidation (malondialdehyde content) was higher in
      all PHA-treated groups, whereas splenic protein oxidation (carbonyl content)
      increased in only the 0.05, 0.1, and 0.2 mmol/kg groups. The total iron content
      in the spleen also showed increases of 88, 135, 168, and 209% at PHA doses of
      0.025, 0.05, 0.1, and 0.2 mmol/kg, respectively. These biochemical changes were
      accompanied by a dose-dependent vascular congestion in the spleen, a
      characteristic feature of aniline toxicity. Although the ratio of organ to body
      weight increased for both testes and heart at the highest dose, striking
      morphological changes were observed only in heart. The cardiac lesions consisted
      of a both acute and resolving multifocal subendocardial necrosis involving
      predominently the left ventricle. Our results suggest that PHA is a splenotoxin
      and thus contributes to the toxicity of aniline, while at a high dose, it is also
      cardiotoxic, perhaps due to anoxia associated with the marked methemoglobinemia.
      These results further support the involvement of oxidative stress in the
      splenotoxicity of aniline which may be caused by its reactive metabolite(s) such
      as PHA.

PMID- 9538116
TI  - Isolation and characterization of a skate retinal GABA transporter cDNA.
AB  - PURPOSE: The inhibitory neurotransmitter gamma-aminobutyric acid (GABA) is
      believed to play a crucial role in the processing of information within the
      vertebrate retina. Extracellular concentrations of GABA are thought to be tightly
      regulated by carrier-mediated transport proteins in neurons and glial cells. The
      purpose of this work was to isolate the gene that encodes one of these transport
      proteins in the skate retina. METHODS: cDNA clones were isolated from a skate
      retinal cDNA library using a mouse retinal GABA transporter (GAT1) cDNA as a
      probe. The PCR technique was used to fill sequence gaps, and 5' and 3' RACE were
      employed to amplify the 5' and 3' untranslated regions. The amplified fragments
      were subcloned into a T-vector. Blots containing RNA from 10 different tissues
      were probed to determine the size of the transcript and the tissue distribution.
      RESULTS: Sequence analysis revealed that the skate retinal GABA transporter cDNA
      shared 72% identity with the mouse GABA transporter-1 at the DNA level and 80%
      identity at the amino acid level. Multiple sequence alignments showed that our
      sequence is closest to the Torpedo GABA transporter-1. Two transcripts, 4.5 and 7
      kb, were detected in retina and possibly brain by RNA blot analysis. Fourteen
      introns were detected in the skate GABA transporter gene. CONCLUSIONS: We
      successfully isolated a full length GABA transporter cDNA from the retina of the
      skate. The size of the full length sequence of the skate retinal GABA transporter
      is in agreement with the size of the smaller transcript detected on RNA blots.
      The larger transcript observed on the RNA blot may be the result of either
      alternative splicing or utilization of a downstream poly A signal.

PMID- 9538117
TI  - Characterization of a point mutation in the hormone binding domain of the
      estrogen receptor from an breast tumor.
AB  - It is clear that growth of the MCF-7 breast cancer cell line is stimulated by
      estrogen and when estrogen is removed, growth slows. We have observed a tumor
      derived from MCF-7 cells that grows in athymic mice in the absence of estrogen
      stimulation. We hypothesized that a mutation in the estrogen receptor (ER) could
      be responsible for this constitutive growth. Using single stranded conformational
      polymorphism (SSCP) and DNA sequencing analysis, we have identified an ER
      containing a point mutation at position 415 (gly to val) within the hormone
      binding domain. The functional activity of this mutant was assessed in vitro and
      in vivo. Using transient transfection into an ER negative breast cancer cell with
      an ERE luciferase reporter gene, we found that both the wild-type and mutant
      receptors have similar efficacy. Additionally, the estrogenic responses were
      blocked by antiestrogens in a concentration related manner. We also found that
      tumors with the mutant receptor show similar growth response in athymic mice as
      wild-type: stimulation with estradiol and inhibition with antiestrogens. We
      conclude that the point mutation at position 415 (gly to val) is not responsible
      for constitutive growth.

PMID- 9538119
TI  - Characterization, cloning and expression of the Tage4 gene, a member of the
      immunoglobulin superfamily.
AB  - pE4 is a rat carcinoma-associated antigen identified by monoclonal antibody E4,
      which was raised against a rat colon carcinoma cell line. This glycoprotein is
      expressed at the surface of all the rat colon carcinoma cell lines tested, as
      determined by immunofluorescence analysis. In contrast, a barely detectable level
      was found on normal adult rat colon and lung and no expression could be detected
      on the other normal rat tissues tested. The corresponding Tage4 gene (tumor
      associated glycoprotein E4) is also expressed in rat colon tumors induced by 1,2
      dimethylhydrazine and in Min mouse intestinal adenomas. The Tage4 gene product is
      closely related to the hepatocellular carcinoma antigen TuAg.1. The Tage4 cDNA
      has been isolated and sequenced. Analysis of the deduced aminoacid sequence
      indicated that Tage4 is a member of the immunoglobulin supergene family. This
      family contains cell adhesion molecules which have wide-ranging functions and
      mediate a variety of homotypic and heterotypic cellular interactions playing a
      general role in cell surface recognition. The Tage4 gene has been mapped to rat
      chromosome 1q22 and mouse 7A2-B1, regions that are homologous to the long arm of
      human chromosome 19. Summary review of our work is presented.

PMID- 9538118
TI  - The phosphatase inhibitors, orthovanadate and levamisole, inhibit induction of
      erythroid differentiation and abrogate the associated inhibition of glycolysis.
AB  - Alterations in protein tyrosine phosphate (PTP), lactate, and fructose 2,6
      bisphosphate (F-2,6-P2) levels have been associated with induced MEL cell
      differentiation and commitment to terminal cell division (TCD). The possible
      relationships of perturbations in PTP metabolism and reduction in lactate
      formation during differentiation were investigated utilizing sodium
      orthovanadate, Na3VO4, primarily an inhibitor of PTP phosphatases, and
      levamisole, considered an alkaline phosphatase inhibitor. Both of these compounds
      were found to effectively inhibit the TCD-associated differentiation induced by
      DMSO, HMBA, and Na butyrate and to abrogate the differentiation-associated
      reduction in lactate accumulation due to these agents. However, they were found
      not to inhibit hemin-induced hemoglobin synthesis which is independent of TCD and
      does not alter lactate metabolism. Two brominated levamisole analogs, L-p
      bromotetramisole and D-p-bromotetramisole, were also found to be inhibitors of
      TCD-associated differentiation and to be effective at even lower concentrations
      than levamisole. The changes in TCD-associated differentiation and lactate
      production exhibited the same concentration-dependence with respect to the
      inhibitors. These findings strengthened the theory that TCD-associated
      differentiation, decreased lactate production, and sensitivity to phosphatase
      inhibitors are all associated. Since the induction of MEL cell differentiation
      has been shown to be associated with, and is thought to be due to, the induction
      of PTP phosphatase activity and Na3VO4 is thought to inhibit the differentiation
      by inhibiting PTP phosphatase activity, the effect of levamisole on PTP levels
      was determined. Levamisole, like Na3VO4, was found to increase the tyrosine
      phosphate levels of proteins of similar molecular weights in intact cells in both
      the presence and absence of a differentiation inducer. Several phosphotyrosine
      containing, similarly sized proteins were particularly affected by
      differentiation induction and by Na3VO4 and levamisole treatment. Changes in the
      levels of tyrosine phosphate-containing proteins of approximately 92-96, 60, and
      38 kd were particularly noticeable. The induction of differentiation reduced PTP
      levels and inhibition of differentiation due to treatment with either Na3VO4 or
      levamisole increased their levels. These data suggest relationships between
      signal transduction pathways involved in differentiation and TCD, the regulation
      of lactate and F-2,6-P2 metabolism, and PTP levels.

PMID- 9538120
TI  - Prognostic significance of cyclin expression in human osteosarcoma.
AB  - To evaluate the distribution of cyclin protein expression, in relation to cell
      proliferation rate and clinical behavior, an immunohistochemical study was
      performed on 92 tumor samples of patients with high grade osteosarcoma (OS). A
      large cyclin A- and cyclin E-positive fraction was found respectively in 59% and
      47% of the osteosarcomas, while immunostaining for cyclin D1 was weak or absent
      in most tumor samples. A positive, statistically significant correlation was
      found between A and E cyclins and Ki67 expression (p<0.001). Disease-free
      survival (DFS) analysis included 69 of the 92 patients. A significantly higher
      probability of metastasis was seen in patients lacking cyclin D1 compared to
      those in which cyclin D1 was positive (p<0.01). Conversely, patients with >40% of
      cyclin A-positive cells relapsed more frequently than those with <40% of cyclin A
      positive cells (p<0.05). The multivariate analysis demonstrated that cyclin A had
      a lower predective risk in terms of disease-free survival as opposed to the loss
      of cyclin D1 that is considered a powerful prognostic factor.

PMID- 9538121
TI  - Expression of vascular endothelial growth factor correlates with tumor
      progression in gallbladder cancer.
AB  - Angiogenesis must occur for malignant tumors to proliferate and vascular
      endothelial growth factor (VEGF) is now believed to be central to this process.
      Immunohistochemical staining for VEGF was performed on surgical resection
      specimens from 50 patients with gallbladder cancer. VEGF-positive rate was 38%.
      Comparison of clinicopathologic parameters between the groups with and without
      VEGF expression showed significant differences in tumor size, lymphatic invasion
      and disease stage. Survival rate was worse in the patients whose tumors
      demonstrated VEGF expression. It is suggested that VEGF is correlated with tumor
      progression and may be used as a prognostic indicator.

PMID- 9538122
TI  - Usefulness of K-ras gene mutation at codon 12 in bile for diagnosing biliary
      strictures.
AB  - Point mutations of the K-ras gene at codon 12 are often detected in the
      pancreatic juice of patients with pancreatic cancer. Detection of these mutations
      may, thus, have diagnostic implications. K-ras mutations may also have diagnostic
      potential for other biliary tumors. We sought to detect K-ras mutations in DNA
      obtained from bile in patients with biliary tract cancers, pancreatic cancer and
      benign biliary disease but who had obstructive jaundice. In 35 patients, bile was
      collected during percutaneous transhepatic choledocal drainage (PTCD) catheters.
      K-ras gene mutations at codon 12 in the samples were examined using mutant-allele
      specific-amplification (MASA). We compared these results with cytological
      analyses of bile. K-ras mutations at codon 12 in bile were detected in 11 of 14
      (79%) of the patients with biliary duct cancer, 3 of 9 (33%) with pancreatic
      cancer but not in patients with gallbladder cancer (n=3), papilla of Vater's
      cancer (n=3) or benign biliary diseases (n=6). In the patients, where cytological
      evaluation did not reveal malignant cells, K-ras mutations in bile were detected
      in 5 of 7 (71%) patients with biliary duct cancer and 2 of 5 (40%) with
      pancreatic cancer. This approach, when used in conjunction with bile cytology,
      may improve the yield in diagnosing suspected malignant tumors of the pancreatic
      biliary system.

PMID- 9538123
TI  - Comparison of variant expression of estrogen receptor mRNA in normal breast
      tissue and breast cancer.
AB  - To investigate whether estrogen receptor abnormalities are associated with
      resistance of breast cancer to endocrine therapy, we compared estrogen receptor
      mRNA between normal breast tissue and carcinoma. Using the RT-PCR, paired cancer
      and normal breast tissue specimens from 15 patients were analyzed. Exon-deleted
      variants were found in both tumor and normal tissue, with differences of variant
      expression between normal and tumor tissue being observed. One patient showed
      multiple deletions in the hormone-binding domain. Alterations in the amount
      and/or kind of variant ER expression may be important in determining the response
      of breast cancer to endocrine therapy.

PMID- 9538124
TI  - Hereditary and sporadic ovarian cancer: genetic testing and clinical implications
      (review).
AB  - The two most common forms of hereditary ovarian cancer are: the breast ovarian
      cancer syndrome, and ovarian cancer associated with HNPCC (hereditary
      nonpolyposis colorectal cancer) syndrome. Studies have shown that these diseases
      may be associated with mutations in a number of tumor suppressor genes, mainly
      BRCA1 and BRCA2. Malfunction of the protein products of these genes have also
      been found to be involved in sporadic ovarian cancer, which makes up the majority
      of ovarian cancer cases. HNPCC-ovarian cancer associated families reveal frequent
      mutations in at least four genes (hMSH2, hMLH1, hPMS1, and hPMS2) involved in the
      repair of mismatched DNA. With ovarian cancer being such an important health
      issue, the push is on to design reliable screening tests to detect defective
      inherited or somatic alleles in individual carriers. So far, most progress has
      been demonstrated in those patients with family histories of the disease who are
      at increased risk. The ramifications of such research may impact a variety of
      scientific, clinical, legal, ethical, and psychosocial issues. In addition to
      current treatment modalities, positive results of these tests may indicate the
      need for increased clinical surveillance, prophylactic treatment, and genetic
      counseling of patients on an individual basis. It remains to be seen whether the
      technology can be made reliable enough to not only benefit high-risk individuals
      but also the general population.

PMID- 9538125
TI  - Comparative in vivo studies with paclitaxel and liposome-encapsulated paclitaxel.
AB  - Our study was designed to evaluate the pharmacokinetics, tissue distribution,
      toxicity and therapeutic efficacy of liposome-encapsulated paclitaxel (LET) in
      comparison to conventional paclitaxel. In normal mice, LET was much less toxic
      than the conventional drug. A dose of 32.5 mg/kg of conventional paclitaxel
      administered i.v. on three consecutive days produced 100% mortality by day three,
      while liposomal paclitaxel exhibited no mortality. The control group which
      received Diluent 12 (Chremophor EL and ethanol; 1:1 v/v), a vehicle used in
      conventional paclitaxel, 30% mortality was observed at this dosage level. In
      murine ascitic L1210 leukemia model, liposomal paclitaxel and conventional
      paclitaxel showed comparable antitumor activity. The pharmacokinetics of
      conventional paclitaxel and LET was studied in mice at dose levels of 5 mg/kg and
      20 mg/kg. After intravenous administration of conventional paclitaxel at a dose
      of 5 mg/kg, the area under the plasma-concentration-time curve (AUC) was 2-fold
      lower and, the elimination half-life was 2-times shorter compared to LET. At a
      dose of 20 mg/kg, the terminal half-lives were comparable, however, conventional
      paclitaxel displayed non-linear pharmacokinetics with disproportionate increase
      in AUC. At the two dose levels studied, LET demonstrated linear kinetics. Tissue
      distribution of paclitaxel after administration of LET showed levels 10-fold
      higher in spleen and 3.5-fold higher in liver as compared to conventional
      paclitaxel. The significant decrease in toxicity shown by LET, coupled with an
      increase in plasma AUC and half-life indicates that LET may be a viable
      alternative to the therapeutic use of the conventional preparation of paclitaxel.

PMID- 9538126
TI  - ELAM selectin expression in breast carcinomas detected by automated and
      quantitative immunohistochemical assays.
AB  - ELAM is an E-Selectin adhesion molecule involved in the inflammatory process but
      it is also thought to potentially participate in the development of blood borne
      metastases, by facilitating tumour cell adhesion to vessels wall. ELAM expression
      in tumours was immunohistochemically investigated in 203 breast carcinomas.
      Frozen tissue sections were probed with monoclonal anti ELAM (Clone 1.2B6) using
      automated and quantitative immunoperoxidase systems. A positive anti-ELAM
      immunoreaction was observed in 113 tumours (57%). The mean surface of positive
      tumours varied from 3% to 50% (mean = 11.75%, SD = 8.7) and was correlated with
      histoprognostic indicators and tumour expression of various antigens detected
      according to the same method as ELAM. The results showed that ELAM
      immunoexpression was independent of the tumour size, grade and type and of the
      nodal status but significantly increased parallel to patients' age (p<0. 01).
      ELAM expression was independent of Ki-67/MIB1, anti-P53 and anti-Bcl2, anti
      CD44v, anti-c-erbB-2, anti-CD31, anti-RE/RP, anti-PS2, and anti-VLA3
      immunoreactions. But ELAM expression correlated with that of the VCAM vascular
      cell adhesion molecule (p=0.0004), VLA2 (p<0.0001), P-glycoprotein (p=0.025), and
      of Cathepsin D to a lower degree (p=0.06) and inversely correlated with E
      cadherin (p=0.03). The results suggest that endothelial cell activation is
      independent of tumour cell proliferative activity and of stromal angiogenesis and
      that the precise role and regulation of ELAM in tumours remains to be elucidated.
      Also the clinical relevance of ELAM immunohistochemical expression requires
      further investigation and correlation with patients' follow-up.

PMID- 9538127
TI  - Differential expression of cytochrome P4502E1 (CYP2E1) in Morris hepatomas and
      livers of tumor bearing rats.
AB  - The objective of this investigation was to determine if the decrease of
      cytochrome P4502E1 (CYP2E1) in hepatomas is related to the tumor growth rate.
      There was a significant correlation between N-nitrosodimethylamine (NDMA)
      demethylase activities and CYP2E1 protein levels in rat liver and hepatomas. The
      levels of NDMA demethylase activities and CYP2E1 protein content were lower in
      hepatomas than in the corresponding host livers. NDMA demethylase activities and
      CYP2E1 protein levels were greater in hepatomas of slow and intermediate growth
      rate than in fast growing hepatomas. A similar trend was also observed with
      CYP2E1 mRNA levels. The results demonstrated an inverse relationship between
      growth rate of rat hepatomas and the expression of CYP2E1.

PMID- 9538128
TI  - nm23 expression in human breast cancer: correlation with cell proliferation (S
      phase) as observed with a double-labeling immunocytochemical-autoradiographic
      technique.
AB  - In 51 unselected breast cancer samples, a double-labeling immunocytochemical
      technique was utilized to observe the phenotypic expression of the nm23 gene
      during S-phase. The feasibility of the method was confirmed by comparison with
      routine evaluations for both thymidine-labeling index and nm23 (p<0.001). No
      correlation was found between the two parameters in the overall series or when
      subgroups regarding menopausal status, nodal involvement, tumor size, hormone
      receptor content were considered. Tumors with a higher nuclear grade showed a
      significant correlation only with TLI (p=0. 02). A trend for an inverse
      relationship between the two parameters was noted but was not statistically
      significant. A significant association between TLI and nm23 expression was found
      by Chi-square test using median values as cut-off. Our data based on
      morphological and in situ observations do not confirm a correlation between nm23
      and cell proliferation, even if this correlation cannot be completely excluded.
      Multicentric trials of high power with these same techniques are still necessary
      to definitely establish the prognostic role of nm23 in breast cancer.

PMID- 9538129
TI  - Mutation of the transforming growth factor-beta type II receptor gene is a rare
      event in human sporadic gastric carcinomas.
AB  - Mutations of the transforming growth factor-beta type II receptor (TGF-beta RII)
      gene have been detected in several human cancers. However, mutation analysis of
      coding sequences of TGF-beta RII in gastric carcinomas has not yet been fully
      elucidated. We performed PCR-SSCP analysis and direct DNA sequencing of the
      entire coding region of TGF- RII in 38 human sporadic gastric cancers and 8
      gastric cancer cell lines. Mutations of the TGF-beta RII were detected in two
      tumors and three cell lines. Two tumors had one base deletion in the polyadenine
      tract in exon 3, the cystein-rich extracellular domain. Three cell lines had a
      silent mutation in the kinase domain located in exon 4. Polymorphisms were
      detected in introns 2 and 3. An a/g polymorphism was observed at the seventh base
      in intron 2 and an a/t polymorphism was observed at the fourth to last base in
      intron 3. There were no mutations in exons 1, 2, 5, 6 and 7. These results
      indicate that the polyadenine tract in the TGF-beta RII is a mutational hot spot
      in human gastric cancer. However, these results also suggest that mutations of
      the gene are rare events in human sporadic gastric cancer.

PMID- 9538130
TI  - Impaired tumorigenicity of IL-4-producing murine neuroblastoma cells in
      immunodeficient nude mice.
AB  - We have examined antitumor effect of murine neuroblastoma cells (C1300)
      retrovirally transduced with interleukin-4 (IL-4) gene in syngeneic A/J and nude
      mice. Although in vitro proliferation of IL-4-secreting C1300 cells (C1300/IL-4)
      was not different from that of wild-type cells, the in vivo tumor growth of
      C1300/IL-4 cells subcutaneously inoculated into immunocompetent A/J mice was
      retarded compared with that of wild-type cells and consequently, the survival of
      the A/J mice which received C1300/IL-4 cells was prolonged. In immunodeficient
      nude mice we observed accelerated growth rate of wild-type tumors in comparison
      with the tumors developed in A/J mice. In contrast, the tumor growth of C1300/IL
      4 cells in nude mice was significantly suppressed and the growth was much slower
      than that of C1300/IL-4 cells inoculated in A/J mice. Thus, the secretion of IL-4
      from tumor cells produced antitumor effect more efficiently in mature T cell
      defective hosts than in immunocompetent mice. Our results suggest a possible
      clinical application of IL-4 expression in tumor cells via genetic manipulations
      especially in immunocompromised cancer patients.

PMID- 9538132
TI  - Decrease in gamma-actin expression, disruption of actin microfilaments and
      alterations in cell adhesion systems associated with acquisition of metastatic
      capacity in human salivary gland adenocarcinoma cell clones.
AB  - In order to clarify how cytoskeletons and adhesion systems change through
      acquisition of metastatic capacity in a cancer cell, we examined the expressions
      of beta- and gamma-actin, the morphology of actin microfilaments and focal
      contacts, and also the expression of vinculin in a salivary gland adenocarcinoma
      cell clone cl-1, which acquired metastatic capacity, in comparison with its
      original clone HSGc lacking metastatic ability. Two-dimensional gel
      electrophoresis of Triton-insoluble fractions and combined Western blot analysis
      by immunostaining with anti actin-isoform antibodies showed that the expression
      of gamma-actin was somewhat lower than that of beta-actin in HSGc, and cl-1
      expressed a comparable amount of beta-actin to HSGc, whereas gamma-actin
      expression by cl-1 was far less than that by HSGc. Northern blot analysis
      demonstrated that there was little difference in the level of beta-actin mRNA
      between HSGc and cl-1, while the level of gamma-actin was markedly decreased in
      cl-1 as compared with HSGc. In terms of morphology, cl-1 cells showed disruption
      of actin microfilaments and a decrease in the size and number of focal contacts
      on the cell surface. Furthermore, cl-1 showed decreased expression of vinculin,
      which became obscured even at the end of actin microfilaments. These results
      demonstrated that a decrease in gamma-actin, disruption of actin microfilaments,
      and suppression of focal contacts as well as vinculin take place in the
      transformation from a non-metastatic condition to a metastatic one in the human
      salivary gland adenocarcinoma cell clones. Thus, it was strongly suggested that
      these changes contribute to a decrease in cell adhesiveness and an increase in
      cell motility, which is probably a major cause for acquisition of metastatic
      potential.

PMID- 9538131
TI  - Loss of merlin-p85 protein complex in NF2-related tumors.
AB  - The NF2 tumor suppressor gene product, designated merlin, belongs to the family
      of molecules that links membranous protein with the cytoskeleton. We have
      previously shown that merlin was co-immunoprecipitated with a cellular protein,
      p85, in cultured cell. To analyze the alteration of merlin and associated
      proteins in surgical specimens, we developed a new method for biotin-labeling of
      whole cellular proteins. Screening of tumor tissues using our method showed that
      none of malignant gliomas and half of the NF2-related tumors had altered p85 and
      merlin. Our detection method seems useful for the screening of merlin alterations
      in NF2-related tumors.

PMID- 9538133
TI  - Fibroblast growth factor-2 and -9 regulate proliferation and production of matrix
      metalloproteinases in human gliomas.
AB  - Fibroblast growth factor (FGF) signaling has been recognized in human gliomas. We
      tested the effect of FGF-2 and FGF-9 on the proliferation and the expression of
      matrix metalloproteinases (MMPs) and their inhibitor (TIMP-1) in vitro. Both FGFs
      showed mitogenic activity on U251MG and NMC-G1 cells. MMP-1 expression and
      collagenolytic activity of NMC-G1 but not of U251MG, and TIMP-1 expression of
      both cells were stimulated by FGFs. MMP-2 expression, gelatinolytic activity, and
      chemoinvasion on the matrigel were not altered. FGFs may regulate proliferation
      and microenvironmental factors independently in each glioma type.

PMID- 9538134
TI  - Hormone receptor measurements and survival in 1335 consecutive patients with
      primary invasive breast carcinoma.
AB  - The distribution of estrogen and progesterone receptors (ER, PR) was assessed in
      the primary tumour in 1335 of 2704 (49%) consecutive new breast carcinoma
      patients (HORMREC). In a subgroup of 757 radically treated patients without
      systemic adjuvant treatment (RADOP) the relation of the ER and PR content to
      relapse and survival was evaluated. Three levels were defined for ER: ER-: <10
      fmol/mg protein, ER+: moderate ER content >/= 10-99 fmol/mg protein, and high ER
      content >/= 100 fmol/mg protein. In 1288 patients of the HORMREC group who were
      evaluable for ER, 1061 (82%) had ER+ tumours, 685 (65%) of moderate content and
      376 (35%) of high content, respectively. Among 917 patients, evaluable for PR,
      723 (79%) tumours were PR+ (>/= 20 fmol/mg protein), of them 352 (49%) with a
      moderate content (>/= 20-99 fmol/mg protein) and 371 (51%) with a high content (
      >/= 100 fmol/mg protein). The median ER content was significantly increased among
      the post-menopausal women as compared to the premenopausal women, whereas the
      median PR content showed no such differences. For the RADOP patients, no
      correlation between ER status and the first site of relapse was seen, whereas PR+
      tumours tended to relapse more often locally than PR- tumours. In the univariate
      analysis the five-and 10-year tumour-related survival rates for all patients were
      not correlated with ER or PR positivity. One subgroup of patients with favourable
      outcome was identified on the basis of hormone receptors: Premenopausal women
      with tumours of moderately elevated ER content. In the multivariate analysis
      tumour size and axillary node status were the only independent predictors of
      survival. Measurements of hormone receptor status give weak prognostic
      information in radically treated patients with breast cancer as long as no
      adjuvant systemic treatment is applied. As todays' adjuvant treatment is based on
      the knowledge of hormone receptor status of the primary tumour, this information
      should be obtained routinely.

PMID- 9538136
TI  - Variable expression on lung cancer cell lines of HLA-A2-binding MAGE-3 peptide
      recognized by cytotoxic T lymphocytes.
AB  - Cytotoxic T lymphocytes (CTL) specific for HLA-A2-binding MAGE-3 peptide
      (FLWGPRALV) were generated by repetitive stimulation of PBMC with the peptide in
      the presence of EBV-transformed B blasts and IL-2. Using these CTL, we
      investigated the expression of the HLA-A2-binding MAGE-3 peptide on lung cancer
      cell lines. Of 14 cell lines investigated, 1-87, PC-9, OU-LC-KI, 11-18 and LK87
      were derived from HLA-A2 positive patients. But cytofluorometry analysis showed
      that 1-87, PC-9 and OU-LC-KI, but not 11-18 or LK87 expressed the HLA-A2 antigen.
      All five cell lines expressed MAGE-3 gene mRNA. Twelve of thirteen CTL lines from
      two HLA-A2 positive donors showed no cytotoxicity against any of the 14 lung
      cancer cell lines. CTL line TI-1 showed cytotoxicity against 1-87 but not against
      any of the other cell lines. Treatment of 1-87 with IFN-gamma greatly augmented
      the cytotoxicity of TI-1 and induced it in the other 12 CTL lines, confirming the
      expression of the peptide on 1-87. No cytotoxicity was induced by IFN-gamma
      treatment of PC-9 or OU-LC-KI. However, PC-9 and OU-LC-KI pulsed with the peptide
      were killed efficiently by all of the CTL lines, suggesting no expression of the
      peptide on those cells. A low level of cytotoxicity was induced on 11-18 but not
      LK87 by IFN-gamma treatment, although expression of the HLA-A2 antigen was not
      observed by cytofluorometry. These findings showed that expression of the HLA-A2
      binding MAGE-3 peptide recognized by CTL was variable on lung cancer cell lines.

PMID- 9538135
TI  - Suppression of cell growth by ectopic expression of N-cadherin.
AB  - We found that ectopic expression of N-cadherin in 3Y1 caused tight association of
      cells and, thereby, substantially suppressed cell growth. N-cadherin expression
      inhibited neither tyrosine phosphorylation of cellular proteins, GTP uptake onto
      Ras, nor activation of MAP kinase, suggesting that it does not directly interfere
      the Ras-MAP kinase pathway. However, co-expression of N-cadherin with dominant
      negative Ras, S17N Ras, showed synergestic growth inhibitory effect, suggesting
      that N-cadherin signaling antagonizes the Ras-MAP kinase signaling. In addition,
      we found that N-cadherin yielded cell-cycle arrest at G0/G1 phase. These results
      strongly suggest that N-cadherin cell adhesion machinery works as a negative
      controller of cell cycle in 3Y1 and this growth suppressive function of cadherin
      is distinct from the epithelial morphogenetic function.

PMID- 9538137
TI  - Aberrant p16INK4 expression related to clinical stage and prognosis in patients
      with pancreatic cancer.
AB  - The p16 tumor suppressor gene is thought to play an important role in cell cycle
      regulation by encoding for protein products that can inhibit the progression from
      G1 to S phase in the cell cycle. Recently, the p16 gene has been found to be
      mutated or deleted in a variety of different types of primary human malignant
      tumors and human-derived malignant tumor cell lines. In this study, primary
      ductal pancreatic adenocarcinomas from 32 human patients were analyzed
      immunohistochemically for expression of p16 protein, with emphasis on the role of
      abberant p16 protein expression as a prognostic indicator. In addition, the same
      tumors were also assessed for p53 protein expression, AgNOR counts, and DNA
      ploidy. Nineteen out of the 32 cases (59%) showed positive immunoreactivity for
      p16 protein in their tumors and a significant association was found between lack
      of p16 protein expression, and both advancing clinical stage classification of
      disease, and poorer survival (p<0.05). The rate of positive immunoreactivity for
      p53 protein expression was 59%, however, no clear association was found between
      p53 protein expression, and either clinical stage of disease, or survival. These
      findings suggest that alteration of the p53 gene may be a relatively early event
      in pancreatic tumorigenesis, whereas alteration of the p16 gene is more likely to
      be correlated with tumor progression in pancreatic malignancies. Further survival
      analysis revealed that all five of the 32 cases that survived for three years or
      longer had positive immunostaining for p16 protein, and a relatively low level of
      AgNOR counts. In four out of five of these patients, the tumors also exhibited
      negative immunostaining for p53 protein and DNA diploidy. These findings suggest
      that molecular analysis of patient tumor sections may yield potentially useful
      prognostic indicators for patients undergoing surgical resection for pancreatic
      cancer.

PMID- 9538138
TI  - Prognostic significance of p53, angiogenesis, and other conventional features in
      operable breast cancer: subanalysis in node-positive and node-negative patients.
AB  - To validate the prognostic value of the determination of p53 expression,
      intratumoral microvessel density (IMD) (a measure of angiogenesis), and the
      conventional features, we studied 531 patients operated of breast cancer (271
      node-positive and 260 node-negative), with a median follow-up exceeding 6 years.
      IMD was assessed by using the anti-CD31 antibody to identify the microvessels.
      p53, estrogen receptor (ER) and progesterone receptor (PgR) were determined by
      immunocytochemistry using the antibodies PAb1801, H-222 Sp2y and KD-68,
      respectively. The prognostic value of the markers was analyzed by univariate and
      multivariate statistical analyses. In the overall series p53 expression, IMD,
      nodal status, ER and PgR were statistically significant prognostic indicators for
      both relapse-free survival (RFS) and overall survival (OS) in the final
      multivariate model. Likewise, tumor size and menopausal status were significant
      prognostic indicators for RFS and OS, respectively. In the subgroup of node
      negative patients who did not receive adjuvant therapy only p53, IMD, and tumor
      size were statistically significant in multivariate analysis. In the subgroup of
      node-positive patients treated with adjuvant chemotherapy, IMD, the number of
      involved nodes and PgR were statistically significant in multivariate analysis.
      In the subgroup of node-positive patients treated with adjuvant tamoxifen, IMD
      and ER (and the number of involved nodes, only for OS) were statistically
      significant for both RFS and OS in the final multivariate model. Different
      markers played a diverse prognostic role in the diverse subgroups studied.
      Angiogenesis was the sole marker which retained prognostic value in all the sub
      groups analyzed. p53 retained significance only in the subgroup of node-negative
      patients, whilst ER and PgR were statistically significant in the subgroups of
      node-positive patients treated with adjuvant hormone therapy or chemotherapy,
      respectively.

PMID- 9538139
TI  - Type II [3H]estradiol binding site antagonists: inhibition of normal and
      malignant prostate cell growth and proliferation.
AB  - A number of studies from our laboratory and others have shown that synthetic and
      naturally occurring bioflavonoids and related compounds have significant
      antiproliferative activity in the rat uterus and mouse mammary tumor model
      systems. This cell regulatory activity is attributed to the fact these compounds
      mimic methyl p-hydroxyphenyllactate (MeHPLA) as ligands for nuclear type II
      [3H]estradiol binding sites. The rodent prostate is also an estrogen target
      tissue which contains type II sites (1,2). Therefore, we assessed the effects of
      2,6-bis((3-methoxy-4-hydroxyphenyl)-methylene)-cyclohexanone (BMHPC) on normal
      and malignant prostatic cell growth and proliferation in vitro and in vivo. This
      cyclovalone is designed to bind to type II sites with high affinity and mimic
      MeHPLA as a cell growth antagonist. Oral administration of BMHPC (9.5-38.0 mg/kg
      body weight per day) to intact adult male Balb/c mice for 14 days resulted in a
      dose dependent reduction (P<0.01) in prostatic weight relative to controls. No
      significant treatment effects of BMHPC on seminal vesicular, testicular or body
      weights were observed. BMHPC also competed for [3H]estradiol binding to type II
      sites in LNCaP and PC-3 human prostatic cancer cell lines and this ligand
      inhibited the proliferation of these cells in a dose and time dependent fashion.
      A direct correlation between type II site occupancy by BMHPC and the inhibition
      of LNCaP or PC-3 cell proliferation was observed which was reversible (not shown)
      following removal of BMHPC from the medium. Flow cytometry studies revealed that
      the type II site antagonist significantly reduced (p<0.01-p<0.001) the numbers of
      LNCaP and PC-3 cells in G0/G1 and caused an accumulation (p<0.001) of these cells
      in S-phase and G2/M (p<0.01). These data suggest that BMHPC blocks mitosis. This
      is consistent with the observed cytostatic activity of BMHPC in a variety of
      model systems. Oral administration of BMHPC to nude mice bearing subcutaneous PC
      3 cell xenografts impeded the growth of these solid tumors in vivo without
      significant signs of toxicity. These findings demonstrate that BMHPC possesses
      significant anti-proliferative activity in normal and malignant prostatic tissues
      and cells, and extend our hypothesis that MeHPLA regulation of cellular
      proliferation via type II binding site interactions is an important pathway
      involved in cell growth regulation.

PMID- 9538140
TI  - P-glycoprotein-mediated multidrug resistance is modulated by pretreatment with
      chemosensitizers in HCT-8 carcinoma cells in vitro.
AB  - The effects of pretreatment with the multidrug resistance (MDR) modulators
      verapamil (VPM), tamoxifen (TMX), cyclosporin A (CsA), and SDZ PSC833 (PSC) on
      drug sensitivity of the P-glycoprotein (Pgp) expressing human ileocecal carcinoma
      cell line HCT-8 is described. Following pretreatment of 2, 16 and 48 h with the
      individual modulators, rhodamine 123 efflux (RHO), transepithelial vinblastine
      transport (VIN) across treated HCT-8 monolayers, and chemosensitivity to
      doxorubicin (DOX) were determined and compared to Pgp protein expression and
      phosphorylation. After 2 h, VPM, TMX, CsA and PSC inhibited RHO efflux and VIN
      transport and increased the chemosensitivity of HCT-8 to DOX significantly.
      Prolonged exposure failed to further increase inhibition of Pgp-mediated
      transport, but in contrast maximized phosphorylation of Pgp (16 h) and Pgp
      protein expression (48 h), respectively.

PMID- 9538141
TI  - Multidrug resistance modulation in rhabdomyosarcoma and neuroblastoma cell lines.
AB  - Four rhabdomyosarcoma and three neuroblastoma cell lines were characterised for
      the presence of P-glycoprotein and MDR-1 expression using immunohistochemistry,
      northern analysis, RT-PCR and in situ mRNA hybridisation. None of the
      rhabdomyosarcoma lines were unequivocally positive in contrast to all three
      neuroblastoma lines. Chemosensitivity to cytotoxic agents was determined using
      the MTT assay and chemosensitisation by cyclosporin and verapamil was evaluated.
      In a single rhabdomyosarcoma line (HX 170) there was sensitisation to etoposide
      using verapamil but not to other drugs or using cyclosporin A. In contrast, in
      all three neuroblastoma lines both cyclosporin and verapamil sensitised to
      vincristine and doxorubicin. No evidence of sensitisation to etoposide was
      apparent. The sensitisation was most marked for vincristine, using either
      modulator and therefore the influence of modulator scheduling was evaluated with
      this drug in the neuroblastoma line SK N BE. Prolonged pre-exposure to modulator
      did not appear necessary and maximum sensitisation was apparent where either
      cyclosporin or verapamil was added 1-3 h prior to and post vincristine.
      Continuity of exposure was important and even a break of 30 min appeared to
      reduce sensitisation. These data confirm the potential for chemosensitisation in
      MDR-1 positive neuroblastoma cell lines and provide some basis for rational
      schedule design in clinical practice. Because of the probability that vincristine
      resistance is predominantly related to MDR-1 and less multifactorial than for
      other drugs such as doxorubicin or etoposide, this agent should be considered for
      inclusion in any clinical evaluation of MDR reversal strategies.

PMID- 9538142
TI  - Pattern of genomic imbalances in oral squamous cell carcinomas with and without
      an increased copy number of 11q13.
AB  - Among 23 squamous cell carcinomas (SCC) of the oral cavity which were screened
      for DNA copy number alterations (CNAs) using comparative genomic hybridization,
      14 showed a gain of, and 5 of these 14 even an amplification of band 11q13.
      Amplification of 11q13 was also detected in three of the four studied SCC cell
      lines and was confirmed by interphase FISH. The number of CNAs in addition to
      11q13 varied from 14 to 47 in these carcinomas. All these tumors had seven other
      specific CNAs in common, i.e. gain on 1p36.3-36.6, 5p15, 9q34, 12p12-13, 14q32,
      19 and 20q, all but one showed also an increase of copy number in 7p22, 8q24,
      10q26, 12q26, 15q24-25, 16p, 16q23-24, 17q and 22q12-qter. These imbalances were
      distinctly rarer in the tumors without CNA in 11q13. Loss of material apparently
      played a minor role in these tumors with gain of 11q13, the most frequent losses
      (3p12-14 and 5q21) being present in 10 of the 14 cases and loss of 9p13-21 in
      5/14 tumors. The three tumors with the highest number of CNAs in addition to
      11q13, were histologically classified as pT4, three of the five tumors with 11q13
      amplification were highly node-positive (pN 2b-2c). Two of the pT4 tumors shared
      as many as 23 specific chromosomal segments affected by CNA. Thus, gain of 11q13,
      though being found at different stages of karyotypic evolution, is apparently
      associated with a rather specific pattern of other CNAs and involved in
      progressed stages of malignancy in oral squamous cell carcinoma. In addition, the
      proportion of patients deceased within one year after diagnosis was clearly
      higher in the group whose tumors showed an increased 11q13 copy number as
      compared to the group without this increase. This could point to an association
      of gain in 11q13 and aggressiveness of the respective tumor.

PMID- 9538143
TI  - Gene expression of fucosyl- and sialyl-transferases which synthesize sialyl
      Lewisx, the carbohydrate ligands for E-selectin, in human breast cancer.
AB  - The adhesion of circulating cancer cells to vascular endothelium is an important
      step in the hematogenous metastasis of cancer. Until recently, it has been
      believed that carbohydrate antigens are expressed on cancer cells, and E-selectin
      is expressed on endothelial cells to effect this adhesion. We investigated the
      gene expression of fucosyl-transferase (Fuc-T) and sialyltransferase (ST), which
      are involved in the synthesis of sialyl Lewisx (s-Lex) in breast cancer by using
      Northern blot analysis. The concentration of s-Lex in the cancerous portion was
      increased, compared to that in the adjacent non-cancerous portion. A correlation
      was found between the concentration of s-Lex and the amount of Fuc-T VI message
      in 9 cases of breast cancer tissue. Expression of the Fuc-T III message was found
      in only one case who expressed s-Lea. No expression of the Fuc-T V or VII message
      was observed. There was no relationship between the concentration of s-Lex and
      the amount of ST3N and ST4 transcripts. Similar findings were obtained from an
      analysis using cell lines derived from human breast cancer. When Fuc-T VI gene
      was transfected to MCF-7 cells, the expression of s-Lex was markedly induced on
      MCF-7 cells, and the attachment of cancer cells to endothelial cells was
      enhanced. These findings suggest that Fuc-T VI is chiefly involved in the
      synthesis of s-Lex on breast cancer cells.

PMID- 9538145
TI  - Tamoxifen-mediated anti-cellular effect against a choriocarcinoma cell line.
AB  - The present study was undertaken to evaluate the efficacy of using steroid
      hormone antagonists tamoxifen and Ru486 for chemotherapy or chemoprevention of
      choriocarcinoma or other less malignant gestational trophoblastic diseases (GTDs)
      such as invasive mole. Using 4 trophoblast cell lines, we have shown that
      tamoxifen (>/= 2 microM) has anti-growth activity on the choriocarcinoma cell
      line BeWo but not on the other cell lines in a time and dose dependent manner
      while Ru486 invariably had no detectable effect. Based on a radioimmunoassay, we
      have been able to detect low levels of estrogen receptors on BeWo (6 +/- 0.4
      fm/mg; Kd=438+/- 73 pM) and JEG-3 (6.55 +/- 1.2 fm/mg; Kd=710 +/- 42 pM) cells
      and progesterone receptors on HT (48.62 fm/mg; Kd=1,690 +/- 182 pM) and TL (8.46
      fm/mg; Kd=1,540 +/- 115 pM) cells. However, there is no definite correlation
      between steroid responsiveness and the presence of the receptors. The mechanism
      of our observed tamoxifen-mediated anti-cellular effect is uncertain and
      characteristics commonly associated with apoptotic cell death were not observed.
      The level of neither wild-type nor mutant forms of the p53 protein correlated
      with sensitivity to tamoxifen. Our results suggest that estrogen may be a growth
      hormone for some trophoblasts and tamoxifen may be potentially useful for the
      treatment of selected cases of choriocarcinoma or other trophoblastic diseases.

PMID- 9538144
TI  - Differential regulation of human NK cell-associated gene expression following
      activation by IL-2, IFN-alpha and PMA/ionomycin.
AB  - Natural killer (NK) cells are important in host-defense mechanisms against
      infection and cancer and also participate in regulation of the immune response.
      The functions of NK cells as well as their maturation and differentiation are
      regulated by various stimuli such as interleukin-2 (IL-2) and interferon-alpha
      (IFN-alpha). The mechanisms by which these stimuli regulate distinct NK functions
      are not known. This study compared the patterns of gene expression for several NK
      associated genes namely perforin (PEF), granzymes A and B (GA or B), IL-1beta,
      IFN-gamma, tumor necrosis factor-alpha (TNF-alpha), CD16 and NK-specific genes,
      NKG2A, NKG5 and NKG7 in both unstimulated and in IL-2-, IFN-alpha and
      PMA/Ionomycin (PMA/I)-stimulated NK cells purified from human peripheral blood.
      IFN-alpha enhanced mRNA expression for PEF, IFN-gamma, TNF-alpha and NKG2A, but
      did not affect NKG7 mRNA expression. IL-2 augmented mRNA expression for PEF, IFN
      gamma, TNF-alpha, NKG2A and NKG7. PMA/I increased mRNA expression for IFN-gamma,
      TNF-alpha and NKG2A but did not affect mRNA expression for PEF and NKG7. Further,
      PMA/I inhibited the expression of CD16 mRNA. These findings demonstrate that the
      three NK-stimuli used share in common the regulation of several genes but each
      regulates specifically other genes. These findings suggest that stimuli-specific
      expression of NK-associated genes may underlie the molecular mechanisms
      responsible for distinct NK-mediated activities induced by different stimuli.

PMID- 9538146
TI  - Neoadjuvant chemotherapy with accelerated CNF plus G-CSF in patients with breast
      cancer tumors larger than three centimeters: a pilot study.
AB  - From February 1992 to November 1993, forty patients with operable breast cancer
      tumors larger than three centimeters were enrolled in this study of accelerated
      neo-adjuvant chemotherapy. Thirty-seven patients are evaluable: one patient was
      excluded from the protocol and two refused to continue treatment after the first
      cycle. Chemotherapy consisted of three presurgical cycles of CNF
      [cyclophosphamide at 600 mg/m2, mitoxantrone (Novantrone) at 10 mg/m2 and 5
      fluorouracil at 600 mg/m2] administered every 2 weeks, plus G-CSF (5 microg/kg
      s.c./day on days 7-12). Twenty-six of 37 patients (70%) achieved objective tumor
      response and were submitted to quadrantectomy. Toxicity was easily manageable.
      After a median 55-month follow-up (range 48-70), no locoregional recurrences were
      observed. Distant metastases occurred in 12/37 (32%) patients. The five-year
      disease-free (DFS) and overall (OS) survival were 58% and 80%, respectively.
      Accelerated CNF plus G-CSF proved to be a safe and tolerable regimen yielding a
      good clinical response thereby increasing the possibility of breast conservation
      surgery for patients otherwise candidates for mastectomy.

PMID- 9538148
TI  - Glycohistochemical properties of malignancies of lung and pleura.
AB  - Based upon the reasoning that protein-carbohydrate recognition is involved in
      diverse intercellular activities including growth control and cell motility 14
      probes have been employed to characterize epitope presence in sections of 80
      cases with operated lung carcinomas, 20 patients with mesothelioma, and 20 cases
      with non-malignant lung diseases. As parts of the innate immune system with
      supposed relevance for host defense the mannan-binding lectin (MBL) and serum
      amyloid P component (SAP) were employed. The naturally occurring immunoglobulin G
      fractions with selectivity for alphaa-galactosides (alpha+) and beta-galactosides
      (beta+) and their subfractions with enhanced target selectivity (alpha+beta
      ,alpha-beta+) allowed the monitoring of expression of reactive sites for these
      autoantibodies as a step to elucidate potential anti-tumor activity. Due to the
      diversity of cellular galactoside-containing glycoconjugates two galectins and a
      plant lectin were included. As a measure of receptor activities for
      carbohydrates, neoglycoconjugates with alpha-galactose, the B-disaccharide, the
      Forssman-disaccharide, and alpha-glucose as histochemically crucial ligand part
      were tested in addition to an antibody against heparin-binding lectin.
      Quantitative image analysis revealed significant differences between cases with
      small cell and non-small cell lung cancer for the plant lectin and one galectin,
      cases with non-tumorous lung disease and lung carcinoma for serum amyloid P
      component and the beta-galactoside-selective autoantibody fraction. Prognostic
      relevance was observed for the presence of glucose-specific sites in small cell
      lung cancer and meso-thelioma cases, and of galectin- and alpha-galactoside
      selective immunoglobulin G fraction-binding sites in non-small cell lung cancer
      patients.

PMID- 9538147
TI  - Advanced nasopharyngeal carcinoma treated with chemotherapy and radiotherapy:
      distant metastasis and local recurrence.
AB  - One hundred and twenty-nine patients with NPC treated at the Department of
      Radiology, Chiba University Hospital and Keio University Hospital from 1980
      through 1993 were selected for this study. Forty-four patients received cisplatin
      (CDDP)- or carboplatin-based chemotherapy, and 58 patients received adriamycin
      (ADM)- and/or 5-FU-based chemotherapy. The remaining 27 patients were treated
      with radiotherapy alone. The median radiation dose to the nasopharyngeal region
      was 64 Gy, and to the initially involved cervical node, 60 Gy. The 5 year
      survival rates for the CDDP, the ADM/5-FU and the radiation alone groups were
      61%, 47% and 42%, respectively. The cumulative incidences of local control in the
      CDDP, the ADM/5-FU and the radiation alone groups were 77%, 49% and 53%
      respectively. The CDDP group achieved the significantly better local control
      (CDDP vs ADM: p=0.001). The overall incidence of distant metastases was 54% in
      the CDDP group. On the other hand, it was 24% in the ADM/5-FU group and 22% in
      the radiation alone group (CDDP vs ADM: p=0.048). While the locoregional control
      rate was significantly better in the CDDP given group, more distant metastases
      were seen in this group.

PMID- 9538149
TI  - Irradiated IL-2 gene-modified plasmacytoma vaccines are more efficient than live
      vaccines.
AB  - The effect of irradiation on the therapeutic efficacy of IL-2 gene-modified
      plasmacytoma cells used as a vaccine in the immunotherapy of parental murine
      plasmacytoma X63-Ag8.653 was examined. Local administration of the IL-2-secreting
      plasmacytoma irradiated with a dose of 50 Gy inhibited i.p. plasmacytoma growth
      more effectively than the administration of non-irradiated, live cell vaccines.
      Whereas the vaccination with the live cell vaccine could substantially prolong
      the survival of the tumour-bearing mice but did not significantly induce tumour
      regressions, the irradiated vaccines could substantially increase the number of
      tumour-free animals. The irradiated vaccines produce higher amounts of IL-2 than
      the live cell vaccines both in vitro and in vivo. Depletion of CD4+ and CD8+
      effector cells with monoclonal antibodies has significantly decreased the effect
      of the vaccination. It can be concluded that both, CD4+ and CD8+ T lymphocytes
      are required for effective IL-2 gene therapy of the X63-Ag8.653 plasmacytoma and
      that the higher effect of the irradiated vaccines is probably due to their higher
      IL-2 production.

PMID- 9538150
TI  - Elevated level of cyclin D1 in mos-transformed cells.
AB  - Mos is a germ cell-specific serine/threonine protein kinase that plays an
      important role during meiotic divisions of oocytes. Upon expression in somatic
      cells, Mos causes cell cycle perturbations leading to neoplastic transformation.
      Mos activates the MAP kinase pathway in both oocytes and transformed somatic
      cells. To determine the mechanism of cell cycle perturbation in mos-transformed
      cells, we examined the status of some key regulators of G1 phase. We provide
      evidence that Mos causes an elevation in the level of cyclin D1 in NIH/3T3 cells.
      As expected from the increased cyclin D1 level, mos transformation of NIH/3T3
      cells caused an increase in the protein kinase activities of cyclin D1-Cdk4 and
      cyclin E-Cdk2 and induced hyperphosphorylation of the retinoblastoma protein. Of
      importance, the level of cyclin D1 was also elevated in eye lens of the c-mos
      transgenic mice compared to normal mice. Our results indicate that the mechanism
      of cellular transformation by Mos involves an elevation in the level of cyclin D1
      in somatic cells.

PMID- 9538152
TI  - Apoptosis regulating genes in prostate cancer (review).
AB  - Prostatic adenocarcinoma is emerging as a major cause of morbidity and mortality
      in the male population in the western world. Programmed cell death (apoptosis) in
      the prostate is activated by hormone ablation and is under the control of several
      regulating genes including the tumour suppressor gene p53 and the proto-oncogene
      bcl-2. Bcl-2 belongs to a rapidly expanding family of genes which form two
      functionally antagonistic groups controlling cell death and survival. Apoptosis
      regulating genes appear to play an important role in the development and
      progression of prostatic adenocarcinoma and offer a potential target for future
      therapeutic strategies.

PMID- 9538151
TI  - Adjuvant therapy for gastric adenocarcinoma with the apoptosis-inducing human
      monoclonal antibody SC-1: first clinical and histopathological results.
AB  - In a first clinical trial with the apoptosis-inducing human antibody SC-1 eight
      patients with poorly differentiated stomach adenocarcinoma of diffuse-type
      received 20 or 30 mg of purified SC-1 antibody intravenously, followed 24 or 48 h
      later by gastrectomy and lymphadenectomy. In seven cases a significant induction
      of apoptotic activity was measured in primary tumors as compared with earlier
      biopsy material and in five patients a significant regression of tumor mass could
      be determined histopathologically. No toxic crossreactivity was observed with
      normal tissue or organs of patients.

PMID- 9538153
TI  - The utility of monitoring carcinoembyronic antigen during systemic therapy for
      advanced colorectal cancer.
AB  - To determine if pre-treatment serum carcinoembryonic antigen (CEA) levels or
      changes in CEA values during treatment have prognostic value, we reviewed five
      prior fluorouracil/leucovorin-based trials and identified 125 colorectal cancer
      patients with no prior chemotherapy for metastatic disease in whom CEA values
      were available. Although pre-treatment serum CEA values did not predict for
      clinical response or time to progression, serial monitoring of CEA appeared to be
      useful in patients with an elevated pre-treatment CEA, particularly when a
      decrease in CEA occurred in concert with radiographic evidence of disease
      response. The CEA nadir was a strong prognostic variable with respect to time to
      disease progression. A consistent rise in CEA values over the minimum value
      signals the need for radiographic re-assessment of the patient's disease status
      to rule out disease progression.

PMID- 9538154
TI  - Identifying predictive factors in melanoma progression.
AB  - Identification of risk factors is a fundamental goal of melanoma studies. The
      current understanding of melanoma progression is based primarily on two-stage
      modeling. A multistate Markov chain process combined with Cox proportional hazard
      regression is used to model the melanoma progression. The model is applied to
      3,434 patients initially diagnosed as AJCC stage I or stage II. Parameter
      estimates are obtained using Cox regression and supplemented by plots of survival
      probabilities. Age is associated with increased risk of progression from stage I,
      II to stage III and from stage III to stage IV. Males experienced an increased
      risk of stage I, II to stage III progression. Primary tumor located on
      extremities decreased the risk of all transitions. Clark's level of invasion >III
      and Breslow's depth >1 mm increased the risk of progression from stage I, II to
      stage III and stage IV. The following interactions among the prognostic factors
      were identified for the first time in this research: interaction of age and
      gender in progression from stage I, II to stage III; interactions of level and
      depth and site by gender were found in the progression from stage I, II to stage
      III; interaction of site and gender in progression from stage III to stage IV and
      stage IV to death. Also we identified primary site as a new prognostic factor for
      the progression from stage IV to death. The study employed a multistate model in
      order to identify prognostic factors relevant for disease progression. The unique
      feature is the modeling of interactions among the prognostic factors and their
      identification.

PMID- 9538155
TI  - Estrogen-induced keratinocyte growth factor mRNA expression in normal and
      cancerous human breast cells.
AB  - The local recurrence rate of breast cancer has been reported to be unusually high
      at the surgical scar. Such breast cancer recurrence is believed to be triggered
      by the release of growth factors into the healing wound. Observations from an
      animal model have also demonstrated that KGF expression is dramatically induced
      by creation of full thickness wounds in mouse skin. Since KGF is an epithelial
      cell-specific mitogen in rat mammary epithelium, it is reasonable to speculate
      that KGF may be also involved in regulating human breast cancer cell growth. The
      purpose of the present study was to determine the effect of estradiol-17 on KGF
      gene expression in normal human breast stromal cells, as well as in human breast
      cancer stromal cells, and the mechanisms by which estradiol-17 regulates breast
      epithelial proliferation. Our results show that KGF expression was not effected
      by estradiol-17 treatment in normal human breast stromal cells. In contrast, KGF
      expression was stimulated by estradiol-17 in human breast cancer stromal cells.
      KGF mRNA levels have also been examined in normal human breast stromal cells and
      human breast cancer stromal cells. An interesting correlation was found between
      KGF expression and estradiol-17 regulation in these cell types. Normal human
      breast stromal cells which do not response to estradiol-17 have lower KGF mRNA
      level than the cancer cells which KGF expression is stimulated by estradiol-17.
      Our data also demonstrate that recombinant human KGF significantly stimulate
      normal human breast and human breast cancer epithelial cell proliferation in a
      dose-dependent manner. Since we have shown that estradiol-17 induces KGF mRNA
      expression in human breast cancer stromal cells, KGF may be involved at least in
      part in the stimulatory pathway that is initiated by estradiol-17 in human breast
      cancer epithelial cells.

PMID- 9538156
TI  - Differential transcriptional activation by the N-terminal region of BRCA1 splice
      variants BRCA1a and BRCA1b.
AB  - The breast and ovarian cancer susceptibility gene BRCA1, is a nuclear
      phosphoprotein which functions as a tumor suppressor in human breast cancer
      cells. BRCA1 protein contains an amino-terminal zinc finger motif and a carboxy
      terminal acidic region. Recently, the carboxy-terminal region of BRCA1 and the
      amino-terminal region of BRCA2 proteins were shown to function as transactivation
      domains when fused to GAL4 DNA binding domain. We have recently isolated and
      characterized two new naturally occurring variants of BRCA1 (BRCA1a/p110 and
      BRCA1b/p100) which are phosphoproteins containing phosphotyrosine that associate
      with E2F transcriptional factors, cyclins and cyclin dependent kinases indicating
      a role for BRCA1 proteins in cell-cycle regulation. Here we show for the first
      time that the amino-terminal region of BRCA1a (BNT) but not BRCA1b can also
      function as a transcriptional activator when fused to GAL4 DNA binding domain.
      Thus, BRCA1/1a proteins contain two autonomous transcriptional activation
      domains, one at the amino-terminal region (BNT) and the other at the carboxy
      terminal region (BCT). BRCA1b retains only the BCT domain since it has lost part
      of the potential BNT domain as a result of alternative splicing. Our results also
      suggest the presence of an inhibitory domain at the carboxy terminal region of
      BRCA1 and BRCA1a proteins (BID). Thus, BRCA1b protein may function as a dominant
      negative variant that could regulate the transcriptional activity of BRCA1/BRCA1a
      proteins and hence may serve as a marker for identifying individuals with greater
      potential for developing breast cancer. It may be possible that loss of
      transcriptional activation or protein-protein interactions in patients with
      mutations in the amino terminal zinc finger domain could deprive the cell of an
      important mechanism for regulating cell proliferation leading to the development
      of breast cancer.

PMID- 9538157
TI  - BRCA1 splice variants BRCA1a and BRCA1b associate with CBP co-activator.
AB  - The tumor suppressor gene BRCA1, is a nuclear phosphoprotein which associates
      with RNA polymerase II holoenzyme. CBP is a component of the holoenzyme.
      Previously, we have characterized two new BRCA1 splice variants BRCA1a/p110 and
      BRCA1b/p100. In the present study, the carboxy-terminal domain of transcription
      factor CBP interacts both in vivo and in vitro with full length BRCA1a and BRCA1b
      proteins as demonstrated by mammalian two- hybrid assays, co
      immunoprecipitation/western blot studies, GST binding assays and histone acetyl
      transferase (HAT) assays of BRCA1 immunoprecipitates from human breast cancer
      cells. Our results suggest that one of the mechanisms by which BRCA1 proteins
      function is through recruitment of CBP associated HAT/FAT (transcription factor
      acetyl-transferase) activity for acetylation of either themselves or general
      transcription factors or both to specific promoters resulting in transcriptional
      activation.

PMID- 9538158
TI  - Quick response of advanced cancer to chemoradiation therapy with antineoplastons.
AB  - Antineoplastons A10 and AS2-1 exhibit growth inhibition of cancer cells by
      diverse modes of action. We observed antitumor responses within 2-3 weeks of a
      combination treatment of chemoradiation therapy and antineoplastons A10 and AS2-1
      in phase I clinical study being conducted in Kurume University Hospital. We
      reviewed 3 clinical cases of advanced cancer (multiple metastatic lung cancer,
      thalamic glioma and primary lung cancer) in which we believed antineoplaston A10
      and AS2-1 may be contributing to the rapid antitumor response. The possible use
      of this combination for induction therapy in advanced cancer is discussed.

PMID- 9538159
TI  - S100 protein serum levels in cutaneous malignant melanoma.
AB  - We investigated the utility of serum S100 determined by means of
      immunoradiometric assay in a cohort of 438 patients affected by cutaneous
      melanoma (126 untreated and 312 previously treated). Using 0.2 microg/l cut-off
      value, determined in 134 healthy blood donors, the sensitivity was 4.2% in stage
      I patients (4/94), 5.3% in stage II patients (1/19), and 38.5% in stage III
      patients (5/13). Even though the sensitivity increased progressively from stage I
      to stage II and III, these differences were not statistically significant. The
      prognostic significance of S100 evaluation at diagnosis was investigated in terms
      of survival but no statistical correlation between S100 basal levels and survival
      was found. In the 312 previously treated patients serum S100 levels were
      correlated to disease extent, high levels of the marker were observed in 42.8%
      (9/21) of patients with local recurrence, in 32% (16/50) of patients with lymph
      node and/or in-transit metastases, in 77.3% (17/22) of patients with distant
      metastases, and in patients with NED, the specificity of the marker was 96.8%
      (212/219). The difference between these groups were statistically significant. In
      conclusion, S100 protein was abnormally high in patients with metastatic
      malignant melanoma. Serial S100 measurements in a follow-up study are necessary
      to test the importance of the protein in the management of patients with
      metastatic malignant melanoma.

PMID- 9538160
TI  - Primary extranodal lymphoma of skeletal muscles: a report of four cases.
AB  - Approximately one-fourth of non-Hodgkin's lymphomas originate in extranodal
      sites. True primary involvement of soft tissues is quite uncommon and only a few
      well-documented cases are reported in the literature. We report four cases of
      primary skeletal muscle lymphoma. Three of the four cases presented with a
      diffuse large B-cell lymphoma. The clinical history of two cases confirmed that
      soft tissue masses should be promptly biopsied, since the differential diagnosis
      comprises benign lesions, as well as sarcoma, primary or metastatic carcinoma,
      melanoma and lymphoma. As lymphomas have to be treated primarily according to the
      tumour histology and disease extent, treatment of primary skeletal muscle
      lymphomas must be planned with these factors in mind. For patients presenting
      with diffuse large cell histology, a CHOP-like regimen alone or a combined
      modality with radiotherapy seem to be proper approaches.

PMID- 9538162
TI  - Effective program designed for long-term surveillance following colonoscopic
      polypectomy of adenomas.
AB  - Eighty-six patients who had adenoma and underwent colonoscopic polypectomy were
      examined by colonoscopy over a long period (mean follow-up time: 5 years) to
      establish an effective long-term surveillance program. The incidence of
      neogenetic lesions in patients with a large monoadenoma (diameter 0.5 cm; LA
      69.7%) and polyadenoma (PA 74.2%) was higher than in those with a small
      monoadenoma (diameter <0.5 cm; SA 27.3%). We found 4 and 2 carcinomas in patients
      with LA and PA, respectively. The high incidence of neogenetic lesions in
      patients with LA (40.7%) and PA (50.0%) did not decrease with the passage of
      time. Long-term surveillance with total colonoscopy should be performed every two
      years in patients with large monoadenoma or polyadenoma for effective detection
      of neogenetic lesions.

PMID- 9538161
TI  - Maternal genistein exposure mimics the effects of estrogen on mammary gland
      development in female mouse offspring.
AB  - Human and animal data indicate that a high maternal estrogen exposure during
      pregnancy increases breast cancer risk among daughters. This may reflect an
      increase in the epithelial structures that are the sites for malignant
      transformation, i.e., terminal end buds (TEBs), and a reduction in epithelial
      differentiation in the mammary gland. Some phytoestrogens, such as genistein
      which is a major component in soy-based foods, and zearalenone, a mycotoxin found
      in agricultural products, have estrogenic effects on the reproductive system,
      breast and brain. The present study examined whether in utero exposure to
      genistein or zearalenone influences mammary gland development. Pregnant mice were
      injected daily with i) 20 ng estradiol (E2); ii) 20 microg genistein; iii) 2
      microg zearalenone; iv) 2 microg tamoxifen (TAM), a partial estrogen receptor
      agonist; or v) oil-vehicle between days 15 and 20 of gestation. E2, genistein,
      zearalenone, and tamoxifen all increased the density of TEBs in the mammary
      glands. Genistein reduced, and zearalenone increased, epithelial differentiation.
      Zearalenone also increased epithelial density, when compared with the vehicle
      controls. None of the treatments had permanent effects on circulating E2 levels.
      Maternal exposure to E2 accelerated body weight gain, physical maturation (eyelid
      opening), and puberty onset (vaginal opening) in the female offspring. Genistein
      and tamoxifen had similar effects on puberty onset than E2. Zearalenone caused
      persistent cornification of the estrus smears. These findings indicate that
      maternal exposure to physiological doses of genistein mimics the effects of E2 on
      the mammary gland and reproductive systems in the offspring. Thus, our results
      suggest that genistein acts as an estrogen in utero, and may increase the
      incidence of mammary tumors if given through a pregnant mother. The estrogenic
      effects of zearalenone on the mammary gland, in contrast, are probably
      counteracted by the permanent changes in estrus cycling.

PMID- 9538163
TI  - The early phase of colon tumorigenesis induced by dimethylhydrazine in ICR mice.
AB  - In order to study the influence of fiber supplements on dimethylhydrazine
      induction of colon tumorigenesis six-week-old CD1 (ICR): Crj mice were injected
      i.m. at a dimethylhydrazine (DMH) dose 10 mg/kg body weight once weekly for 10
      weeks with or without dietary supplementation with 3% polydextrose, lactosucrose
      or cellulose, or 3% polydextrose and 3% cellulose in combination. There were no
      significant differences in colon tumor induction among the groups. However,
      microadenomas were observed 10 weeks after the first treatment of DMH so that
      this protocol may be useful for studies of the early phase of colon
      carcinogenesis in mice.

PMID- 9538164
TI  - In vitro gene transfer in mammalian cells via a new cationic liposome
      formulation.
AB  - A new cationic liposome formulation of sphingosine (SP) and
      dioleoylphosphatidylethanolamine (DOPE) was developed as an efficient
      transfection reagent. This SP/DOPE liposome showed efficient transfection in a
      wide variety of mammalian cancer cells. No significant cytotoxicity of the
      SP/DOPE liposome to cells was observed. The tranfection activity was greater than
      that of a well-reported liposome which was made from a cholesterol derivative
      3beta-[N-(N',N'-dimethylaminoethane)-carbamoyl] cholesterol (DC-Chol) and the
      neutral lipid DOPE. In addition, the SP/DOPE liposome was found to be less toxic
      to cells than the DC-Chol/DOPE liposome. Stable transfections mediated by SP/
      DOPE liposome were also demonstrated. These results suggest that the SP/DOPE
      liposome may provide a good gene delivery system to be used in the human cancer
      gene therapy.

PMID- 9538165
TI  - The relationship between homovanillic/vanillylmandelic acid ratios and prognosis
      in neuroblastoma.
AB  - A total of 44 cases with neuroblastoma cases (excluding true positive cases
      detected in mass screenings) who were born from 1979 to 1991, and had data
      concerning the clinical stage and values of vanillylmandelic acid (VMA) and
      homovanillic acid (HVA) at diagnosis (microg/mg creatinine) were followed up
      until the end of 1994. Deaths were confirmed using the record of vital statistics
      of the Hokkaido Government. The 60-month survival rate of those who had an
      HVA/VMA ratio of 1-2 was 80.0%. Conversely, those with ratios <1 or >2 had
      respective survival rates of 24.1% and 5.3%. Most of those with a ratio >2 died
      within 24 months of diagnosis. Many of the cases with a ratio <1 lived over 12
      months but died within about 36 months. Many tumors of those cases with a ratio
      of 1-2 originated in extra-adrenal glands, and had negative n-myc amplification.
      Most of the patients with a ratio >2 were diagnosed at 1 year of age or older.
      The HVA/VMA ratio at diagnosis is useful in estimating both the survival period
      and the prognosis.

PMID- 9538166
TI  - Assessment of small intestinal damage in patients treated with pelvic
      radiotherapy.
AB  - Pelvic radiotherapy almost always induces intestinal symptoms. We investigated
      the radiation-induced damage to the small intestinal mucosa and evaluated its
      relationship with symptoms, using cellobiose/mannitol permeability test (CE/MA)
      and plasma postheparin diamine oxidase test (PHD) in 20 patients treated with
      pelvic radiotherapy. The symptoms developed during radiotherapy were noted.
      Intestinal permeability significantly (p=0.013) increased from 0.021 +/- 0.026 to
      0.047 +/- 0.055 (mean +/- SD) after 15 days of radiotherapy, while it returned to
      normal values (0.010 0.015) at the end of radiotherapy. PHD values did not
      change. All patients developed intestinal symptoms. These findings indicate that
      pelvic radiotherapy induces an early small bowel mucosa damage followed by
      mucosal adaptation. Acute intestinal symptoms during pelvic radiotherapy may not
      depend only on small intestinal mucosal damage.

PMID- 9538167
TI  - Long-term prognostic value of PCNA labeling index in primary operable breast
      cancer.
AB  - Cell proliferation was evaluated in 167 tissue specimens obtained from primary
      breast cancer patients who had undergone radical surgery between 1984 and 1988.
      Formalin-fixed and paraffin-embedded tissue specimens were used in the
      immunohistochemical study. The immunohistochemical method was carried out using
      the avidin-biotin immunoperoxidase technique, and anti-proliferating cell nuclear
      antigen (PCNA) monoclonal antibody was used for primary antibody. Based upon the
      PCNA labeling index (LI), the patients were divided into two groups: low PCNA,
      <25% and high PCNA, >/= 25%. The PCNA LI ranged from 1% to 76% (mean, 23.9%).
      Patients aged </= 50 showed significantly higher PCNA LI than those of > 50
      years. There was no relationship between the PCNA LI and tumor size, lymph node
      involvement and hormone receptors. The survival curves of 146 invasive breast
      cancer patients showed that the high PCNA group had poor overall survival
      compared with the low PCNA group. A significant difference in the overall
      survival between the high and low PCNA groups was observed in lymph node-positive
      patients, however, no significant difference was found between the two groups in
      lymph node-negative patients. PCNA LI was identified as an independent predictor
      in primary breast cancer patients.

PMID- 9538168
TI  - Analysis of recovery time indexes in 5-fluorouracil-treated cancer patients.
AB  - Based on our previous experience in doxorubicin-treated patients, in whom we
      observed a significant increase of ventricular recovery time indexes, we analyzed
      these non- invasive parameters of myocardium electrical instability in forty
      three 5-fluorouracil-treated patients, to test the hypothesis of a
      mechanoelectrical disarrangement occurring in 5-fluorouracil (5FU)
      cardiotoxicity. All patients enrolled were studied at the first presentation and
      following chemotherapy. The study showed the absence of any significant changes
      in recovery time indexes or in other electrocardiographic parameters. Our data
      suggest that 5FU does not interfere with electrical properties of myocardial
      fibers.

PMID- 9538170
TI  - Rapid DNA quantification method in microplates using daunorubicine fluorescence
      quenching.
AB  - We have developed a rapid, sensitive and inexpensive method to quantify DNA in
      crude extracts or PCR reaction products using daunorubicine fluorescence
      quenching. We obtained a linear standard curve from 4.7 ng to 600 ng DNA and no
      interaction was observed in the presence of proteins.

PMID- 9538169
TI  - Serum levels of interleukin-6 as a prognostic factor in advanced non-small cell
      lung cancer.
AB  - Serum levels of interleukin-6 (IL-6) were evaluated in a group of advanced non
      small cell lung cancer (NSCLC) patients using an enzyme-linked immunosorbent
      assay. The data were related to clinical status and to cisplatin-based
      chemotherapy response. The mean IL-6 concentrations were higher than the controls
      (p<0.0001); patients with metastatic tumor had higher levels than those with
      undisseminated disease (p<0.006). Tumor progression was associated with an
      increase of IL-6 levels. Patients who responded to chemotherapy had lower serum
      IL-6 levels compared with unresponsive patients (p<0.0001). These data suggest
      that NSCLC patients with high levels of IL-6 have a worse clinical outcome and
      may manifest resistance to cisplatin chemotherapy.

PMID- 9538171
TI  - Desmoid tumour of the breast.
AB  - We describe the clinical and pathological features of a case of desmoid tumour of
      the breast. The lesion was approximately 3.0 cm in greatest dimension.
      Histologically, it had infiltrating borders and extended to the pectoral muscle.
      The differential diagnosis is discussed.

PMID- 9538172
TI  - Carcinoembryonic antigen level in peritoneal washing is a prognostic factor in
      patients with gastric cancer.
AB  - This study was designed to evaluate the usefulness of carcinoembryonic antigen
      (CEA) and sialyl-Tn antigen (STN) levels in peritoneal washings in gastric cancer
      patients. At the time of laparotomy, peritoneal washings were collected from 96
      gastric cancer patients and CEA and STN levels were determined. Patients with
      elevated CEA (100 ng/g protein) had a high incidence for peritoneal metastasis,
      lymph node metastasis and serosal invasion. In addition, prognosis in patients
      with high CEA level was significantly poorer than in those without it. The
      peritoneal CEA is a prognostic factor in patients with gastric cancer.

PMID- 9538173
TI  - Survival of chemo-radiotherapy-treated and thermotherapy-treated patients with
      unresectable lung cancer.
AB  - Prognosis and survival of unresectable lung cancer patients is poor. The 5-year
      survival varies from 3 to 15% without relevant differences between treated and
      non-treated patients. The 2-year survival of comparable patients treated with
      chemo-radiotherapy (CH-RT) (n=63) and thermotherapy (RFT) (n=40) was studied. The
      2-year follow-up survival curves did not differ for the groups in general but the
      survival time was longer for stage IV and non-small cell lung cancer in the RFT
      group (13.2 mo and 13.4 mo, respectively) compared with CH-RT-group (8.4 mo and
      9.6 mo, respectively). The difference was highly statistically significant
      (p<0.005).

PMID- 9538175
TI  - TNF, IL-1 and IL-6 in circulating blood after total-body and localized
      irradiation in rats.
AB  - The levels of TNF, IL-1 and IL-6 in circulating blood of female WAG/Rij rats were
      assessed both after total-body irradiation (TBI) and localized irradiation of the
      right hind leg. The results show that enhanced levels of IL-1 in the circulation
      reflect a stress situation presumably resulting from handling and halothane
      anesthesia of the animal. Neither localized irradiation nor TBI resulted in
      further enhanced levels of IL-1. Both TBI and localized irradiation, lead to a
      small but significant increase in IL-6 levels in serum from circulating blood.
      After TBI this increase dissipated rapidly, 24 h after TBI increased levels are
      not found. After localized irradiation IL-6 levels remain elevated for a longer
      period. Still two weeks after irradiation, the longest time investigated,
      increased levels were observed. We did not observe increased TNF levels after
      localized irradiation or after TBI.

PMID- 9538174
TI  - Relationship between matrix metalloproteinase expression and tumor angiogenesis
      in human breast carcinoma.
AB  - Intratumoral proteases are known to be involved in not only tumor cell invasion
      but also a variety of stromal reactions including neovascularization. In this
      study, we have examined the expression of matrix metalloproteinases (MMPs) by
      gelatin gel zymography and compared its expression with angiogenesis activities
      including the expression of several endothelial growth regulators and
      intratumoral microvessel density (MVD) in human breast cancer tissues. There was
      a significant correlation between activated MMP-2 expression and vascular
      endothelial growth factor (VEGF) expression (p=0.045). In addition, the
      expression of activated MMP-9 expression was significantly correlated with
      thymidine phosphorylase (TP) expression (p=0.0044). Pro MMP-9 expression tended
      to correlated with the increment of MVD (p=0.063). MMP-2 and MMP-9 expressions
      were frequently co-upregulated with endothelial growth regulators in human breast
      cancer tissues, which underlines the cooperative function of MMPs in
      neovascularization.

PMID- 9538176
TI  - Recurrent cystic radiation necrosis of the brain.
AB  - Cystic radiation necrosis is a rare complication of radiotherapy for
      nasopharyngeal carcinoma. The magnetic resonance imaging (MRI) characteristics
      have not been described. Serial MRI images were done on a patient who developed
      multiple cysts in the brain as a result of irradiation for his nasopharyngeal
      carcinoma. The characteristic MRI features included a slightly higher T1-weighted
      signal than cerebrospinal fluid, surrounding white matter edema as indicated by
      the high T2-weighted signal, and absence of gadolinium enhancement on the cyst
      wall. The adjacent gray matter in the anterior temporal lobes and inferior
      frontal lobes, which were included in the radiation field, had gadolinium
      enhancement. Dosimetry data and isodose contour maps revealed that his frontal
      lobes and anterior temporal lobes received 7920 cGy and 5040-6480 cGy of
      radiation respectively. Despite placement of multiple cysto-peritoneal shunts for
      decompression, new cysts eventually developed and previously shunted cysts
      enlarged in size. The management of cystic radiation necrosis of the brain
      remains unsatisfactory.

PMID- 9538177
TI  - Prognosis for patients with pneumonectomy or lesser resections for non-small cell
      lung cancer based on histologic cell type.
AB  - Contrary results have been reported regarding prognosis by histologic cell type
      in surgical treatment for lung cancer. To evaluate whether histologic cell type
      has influence on prognosis, we separately analyzed the prognostic outcome of
      patients who had undergone pneumonectomy (n=119) and lesser resections (n=124)
      for non-small cell lung cancer (NSCLC) between January, 1985 and March, 1996. The
      pneumonectomy group included 87 (73%) squamous cell carcinoma (Sq), 25 (21%)
      adenocarcinoma (Ad) and 7 other types with 10 (8%) patients in postoperative
      stage I of the disease, 29 (24%) stage II, 74 (62%) stage III and 6 in stage IV.
      The lesser resection group included 45 (36%) Sq, 63 (51%) Ad and 16 other types
      with 71 (57%) patients in stage I, 9 (7%) stage II, 32 (26%) stage III and 12
      stage IV. In patients with stages I-III, the 5-year survival rate was 42.8% for
      the Sq group and 41.1% for the Ad group in the case of lesser resections and
      37.1% for the Sq group and 0% for the Ad group (p<0.05) in the case of
      pneumonectomy. The poorer prognosis for patients with Ad in the case of
      pneumonectomy was suspected to be due to the N factor; the percentage of patients
      with N0-1 was significantly lower in the Ad group than for the Sq group (28 vs
      62%, p<0.005). Histologic cell type can be a prognostic factor for patients
      undergoing surgical treatments for NSCLC. One possible reason for the contrary
      results on prognosis by histologic cell type among investigators may be due to
      the mixed results of pneumonectomy and lesser resections.

PMID- 9538178
TI  - Cytotoxic activity of normal mouse serum on mouse tumor cells in vitro.
AB  - Cytotoxic effects of normal mouse serum on mouse tumor cells were investigated in
      vitro. When FE melanoma cells of C57BL/6 mouse origin, were cultured in medium
      containing 1% fetal calf serum (FCS) and 10-30% C57BL/6 mouse serum, number of
      viable FE cells markedly decreased after a little increase in their number,
      indicating cell death of FE cells in culture with mouse serum. Phase-contrast
      microscopic examination showed appearance of fatty degeneration in FE cells after
      24 h, and an increase in cell death after 48 h. Electron microscopic examination,
      and agarose gel electrophoresis of DNA at 72 h of culture showed that their cell
      death occurred as necrosis. This cytotoxic effect of mouse serum was also found
      in culture of combinations of C57BL/6 mouse serum and C57BL/6 mouse melanoma
      cells (G6 cells), and BALB/c mouse serum and various BALB/c mouse tumor cells (G
      5 and G-1 liver tumor cells, and Colon 26 cells). Furthermore, sera of BALB/c and
      B10D2 mice also showed the cytotoxic effect on FE cells. The cytotoxic effect of
      mouse serum was not ascribed to complement activity because all mouse sera were
      treated at 56 degrees C for 30 min before use, and this heat treatment completely
      abolished complement activity, and because serum of C5-deficient mice also showed
      the cytotoxic effect. This cytotoxic activity was stable at heat treatment at 100
      degrees C for 10 min, and was in a serum fraction of molecular weights more than
      30,000 dalton. The present results show that normal mouse serum has a factor(s)
      inducing fatty degeneration and necrosis of mouse tumor cells.

PMID- 9538179
TI  - Studies on hyperthermia combined with arterial blockade for treatment of tumors:
      (Part I) effectiveness of hyperthermia combined with arterial ligation.
AB  - Arterial ligation was combined with hyperthermia in rabbits with VX2 tumors
      implanted in the leg. For seven days after arterial ligation, blood flow was
      decreased and the pH was low in both normal muscle and tumor tissue. The
      temperature of normal muscle and tumor tissue increased faster and reached a
      higher level on heating immediately after ligation than without ligation. The
      antitumor effect of hyperthermia was stronger immediately after ligation than two
      or seven days afterwards. However, damage to normal muscle was severe with this
      combination therapy, so a better method of therapeutic arterial blockade is
      needed.

PMID- 9538180
TI  - Studies on hyperthermia combined with arterial blockade for treatment of tumors:
      (Part II) effectiveness of hyperthermia combined with arterial embolization using
      degradable starch microspheres.
AB  - The efficacy of temporary arterial embolization using degradable starch
      microspheres combined with hyperthermia was investigated in rabbits bearing VX2
      tumors. Microsphere injection caused a marked decrease of tumor blood flow and
      pH. During heating, there was a marked increase of the maximum temperature in
      tumor tissue compared with normal muscle. Tumor growth was suppressed 330% times
      at 3 weeks after hyperthermia alone and 270% times following combined treatment
      with microspheres and hyperthermia. Damage to normal muscle tissue was mild. In
      conclusion, this combination therapy may be useful for causing selective tumor
      damage and reducing the effect on normal tissues.

PMID- 9538181
TI  - Studies on hyperthermia combined with arterial therapeutic blockade for treatment
      of tumors: (Part III) effectiveness of hyperthermia combined with arterial
      chemoembolization using degradable starch microspheres on advanced liver cancer.
AB  - Arterial chemoembolization using degradable starch microspheres and adriamycin
      was combined with hyperthermia to treat advanced liver cancer. The prolonged peak
      adriamycin level in hepatic venous blood suggested that the drug persisted for
      longer in the liver after injection containing microspheres. Heating efficiency
      was increased more in tumor tissue than in normal liver tissue after
      embolization. This combined therapy was performed in eight patients with advanced
      liver cancer and was effective in three (complete or partial remission). The mean
      survival time was 25 weeks and there were no severe side effects. This combined
      therapy may be useful for liver cancer.

PMID- 9538183
TI  - Screening of potential cancer-preventing chemicals for inhibition of induction of
      ornithine decarboxylase in epithelial cells from rat trachea.
AB  - Sixty-one selected chemicals were evaluated in rat tracheal epithelial (2C5)
      cells for their capacity to inhibit induction (or inhibit directly) the enzyme
      ornithine decarboxylase, the activity of which is associated with cell growth and
      division. a-Difluoromethylornithine (DFMO) was used as a positive control. At non
      toxic concentrations, six test compounds had substantial activity (values for
      IC50 DFMO/IC50 compound >1): N-(2-carboxyphenyl)-all-trans-retinamide, ZK 119010
      ?2-(4-hydroxyphenyl)-3-methyl-1-[6-(1-pyrrolidinyl)hexyl]-1H-indol-5- ol?,
      curcumin, 18-a-olean-12-ene-3 ,23,28-triol, genistein and phenethyl
      isothiocyanate. These should be considered for further development as cancer
      preventive agents.

PMID- 9538182
TI  - Value of peritoneal cytology after hysteroscopy in surgical stage I
      adenocarcinoma of the endometrium.
AB  - Nineteen clinical stage I adenocarcinoma of the uterus with favourable
      histological prognosis factors (low grade, no myometrial extension, and no pelvic
      node involvement) were diagnosed using a pre-operative hysteroscopy. During the
      laparotomy, peritoneal cytology was performed systematically. The frequency of
      positive peritoneal washings was abnormally high (7 cases) with cytologic
      findings showing grouped cells in large clusters. However, these patients have
      not experienced peritoneal recurrences. The endoscopic procedures may have
      facilitated the transtubal malignant cell dissemination and are questionable in
      endometrial carcinoma.

PMID- 9538184
TI  - Onset of hepatocellular carcinoma in a non-cirrhotic patient affected with
      haemochromatosis.
AB  - The increased incidence of hepatocellular carcinoma in patients affected with
      haemochromatosis has previously been attributed to cirrhosis. However, some cases
      of hepatocellular carcinoma without cirrhosis have recently been reported in
      patients with haemochromatosis, leading to reconsideration of the role of iron in
      the tumorigenesis of hepatocellular carcinoma. We describe a 79 year old male
      patient affected with haemochromatosis and with a multinodular hepatocellular
      carcinoma, but without any evidence of cirrhosis. The absence of any other cancer
      risk factor (alcohol abuse, liver viral infections, heredity) has lead us to
      reconsider the possible role of iron as a direct carcinogen in the onset of
      hepatocellular carcinoma in patients with haemochromatosis.

PMID- 9538185
TI  - Effect of oyster mushroom (Pleurotus ostreatus) on pathological changes in
      dimethylhydrazine-induced rat colon cancer.
AB  - The effect of 5% of dried oyster mushroom (Pleurotus ostreatus) in the diet on
      the dimethylhydrazine (DMH)-induced colon carcinogenesis was studied in male
      Wistar rats. DMH in a dose of 20 mg/kg of body weight was applied to animals once
      a week during a period of 12 weeks. Mushroom diet was applied either after
      treatment with DMH for another 21 weeks or during the whole experiment. Mushroom
      diet reduced significantly the incidence of lymphoid hyperplasia foci when
      mushroom was supplemented during the whole experiment. Tumour lesions could be
      characterized either as carcinoma in situ, or as infiltrating adenocarcinoma.
      Mushroom diet did not affect significantly the incidence of tumours.
      Nevertheless, a reduction in total number of tumours was observed in both groups
      of animals fed mushroom diet. A significant reduction of the number of tumour
      foci of the type carcinoma in situ was observed in animals fed the oyster
      mushroom during the whole experiment. Also these animals had the significantly
      lower number of aberrant crypt foci. Mushroom diet reduced the ornithine
      decarboxylase activity in the colon and in the liver when oyster mushroom diet
      was administered during the whole experiment.

PMID- 9538186
TI  - Myofibroblastoma associated with bilateral gynecomastia: a case report and
      literature review.
AB  - Myofibroblastoma of the breast is a recently recognized benign mesenchymal
      mammary tumor that typically occurs as a unilateral, solitary lesion.
      Myofibroblastomas are well-circumscribed, unencapsulated tumors characterized by
      spindle cells in fascicles which exhibit varying degrees of myogenic and
      fibroblastic differentiation. Our case reports a mammary myofibroblastoma
      occurring in an 82-year-old male with gynecomastia and reviews the reported
      incidence of this benign spindle cell tumor in the world literature.

PMID- 9538187
TI  - NM23 gene product expression does not predict lymph node metastases or survival
      in young patients with colorectal cancer.
AB  - NM23 gene product is a putative metastases suppressor gene which has structural
      homology to a nucleoside diphosphate kinase. Previous studies examining the
      relationship between NM23 gene product expression and survival in patients with
      colorectal cancer have revealed conflicting results. However, no study has
      focused on young patients with colorectal cancer. This study was carried out to
      determine if expression of the NM23 gene product was correlated with metastatic
      potential and survival in young patients (45 years and under) with colorectal
      cancer. Eighty- one patients with colorectal cancer were studied and the presence
      of the NM23 gene product (H1) was detected using standard immunohistochemical
      techniques. NM23 gene product expression did not correlate with tumour stage,
      lymph node involvement by tumour, presence of distant metastases, extramural
      vascular invasion or degree of tumour differentiation. Independent risk factors
      for overall survival were: Dukes' stage (p=0.00001) and extramural vascular
      invasion (p=0.003). NM23 expression was not an independent prognostic indicator
      (p=0.55). Therefore, NM23 expression does not correlate with existing indicators
      of tumour aggressiveness and behaviour nor is it an independent predictor of
      survival in young patients with colorectal cancer.

PMID- 9538189
TI  - Autoantibodies, autoimmunity and cancer (review).
AB  - There is a strong association between neoplasms and autoimmune diseases. Numerous
      autoimmune phenomena have been reported in malignancies and conversely: malignant
      tumors are diagnosed in increasing frequency in autoimmune conditions. We review
      the most common autoimmune diseases and autoantibodies found in malignancies,
      discuss the therapeutic role of these autoantibodies in cancer, and summarize the
      current knowledge on malignant transformation in autoimmunity.

PMID- 9538188
TI  - Relationship between the oncogene activation profiles and the tumor suppressor
      gene inactivation profiles in 19 human neoplasias - a regression analysis study
      of the intercancer linkage with the world cancer incidence data.
AB  - This study represents an extension of our statistical studies of age-adjusted
      incidence rates (AAIRs) of 19 neoplasias from 47 population units of the world.
      We have invented 2 data manipulation methods (topological data conversion and
      sequential regression analysis method) to estimate separately the intensities of
      each oncogene activation and tumor suppressor gene inactivation of a given tumor
      (marker tumor) relative to a counterpart tumor (reference tumor) in terms of r
      seq value. This study prepared the r seq table of all permutations of tumor pairs
      for each of the 2 cancer genes and for each sex first, and then investigated the
      relation between the r seq profile of oncogene activation and that of tumor
      suppressor gene inactivation for each tumor. A profile containing 16 (male) or 17
      (female) r seq data was prepared for each tumor pair, for each cancer gene, and
      for each sex. The extent of similarity between 2 r seq profiles was assessed by
      the 1st order regression analysis in terms of the correlation coefficient r
      value. Results obtained are given as follows: a) The proportions of both the
      tumor pairs with r seq values of less than -0.90 in the oncogene activation
      tables of two sexes and those with r seq values of more than +0.90 in the tumor
      suppressor gene inactivation tables of the two sexes were all more than 50%. A
      small number of tumor pairs in both the oncogene activation tables and the tumor
      suppressor gene inactivation tables have invaded deep into each the plus- and the
      minus-areas to constitute the very end of long tails of the r seq profiles. b) In
      spite of the above symmetry of data distribution between the 2 cancer-gene
      tables, individual cancer pairs very rarely gave 2 cancer-gene profiles that fit
      the definition of symmetry. Taken together, our data manipulation was a success
      in presenting an oncogene activation profile and a tumor suppressor gene
      inactivation profile separately. c) The similarity test was conducted with all
      combinations of tumor pair profiles for each cancer gene and for each sex. The
      frequency distributions of r values in the oncogene activation tables of both
      sexes looked normal with long tails to both the plus- and the minus-areas. In
      contrast, the corresponding frequency distributions of r in the tumor suppressor
      gene inactivation tables of both sexes were skewed towards the direction of +1.0.
      It was indicated that the morphological specificity of the oncogene activation
      profiles was much higher than that of the tumor suppressor gene inactivation
      profiles. d) Male versus female comparison in 2 neoplasias with sex
      discrimination of cancer risk revealed that the combination of the general
      depression of r seq values in the oncogene profile of dominant gender and the
      general elevation of r seq values in the oncogene profile of recessive gender was
      the common trait of female-dominant breast cancer and male-dominant laryngeal
      cancer. It is suggested that the predominance of oncogene activation impact over
      the tumor suppressor gene inactivation impact was implicated in the creation of
      sex discrimination of cancer risk. e) Application of a new test method
      (reciprocal regression analysis) to the r seq table data led to the conclusion
      that the 2 cancer genes are interfering with each other, and that the balance of
      power between the 2 cancer genes varies from one marker tumor to the other. f)
      The results obtained in this study together with the consistency of data
      interpretation is discussed in light of thermodynamics.

PMID- 9538190
TI  - Immunohistochemical detection of p53 protein in neoplastic, preneoplastic and
      normal bronchial mucosa specimens obtained during diagnostic bronchoscopy.
AB  - The expression of p53 protein was evaluated immunochemically in cancer tissue,
      preneoplastic lesions and normal bronchial mucosa obtained during diagnostic
      bronchoscopy from 53 patients with lung cancer and 12 patients with benign lung
      diseases. In lung cancer patients, positive p53 staining was detected in 26/53
      (49%) of the tumour specimens. In preneoplastic lesions p53 positive staining was
      found in 8 of 24 (33.3%) squamous metaplasia, 1 of 4 hyperplasia and 1 of 3
      dysplasia lesions. In the same group of patients, 12 cases were found with
      positive p53 cells in normal bronchial mucosa. In patients with benign diseases,
      positive p53 staining was found in 1 of 4 cases with squamous metaplasia and in
      one normal mucosa. Our results provide evidence that somatic genetic alterations
      may occur in early stages of lung tumorigenesis, raising the possibility that
      molecular analyses is useful in the early diagnosis of precancerous lesions of
      the bronchial mucosa, and results indicate that p53 expression can be studied in
      small tissue specimens obtained during bronchoscopy.

PMID- 9538191
TI  - Descriptive epidemiology of lymphatic malignancies in Greater Bombay.
AB  - Lymphoid malignancies as a group constitute one of the important cancers met in
      India as elsewhere in the world, but while information on incidence, mortality,
      survival and trends, are available from most of the developed countries, there
      are very few reports available from the rest of the world. The basic data
      utilized for this study was obtained from the Bombay Cancer Registry, the first
      population based registry to be established in India. Descriptive epidemiology of
      these malignancies was obtained by utilizing 5-year data of incidence and
      mortality of different cell types in males and females. For studying time trends
      in the incidence of these cancers, data of the past 30 years has been used. As a
      group, the lymphatic malignancies represent only 5% of the incidence and 3.9% of
      the mortality of the total number of cancers in Greater Bombay. Males in general,
      seem to be more affected by lymphomas than females. Non-Hodgkin's lymphomas are
      the commonest lymphatic malignancies to be detected in Bombay. The incidence
      curves show striking difference in lymphatic malignancies by cell type. In Bombay
      the incidence of these cancers was found to be the highest in the Parsis. Our
      data indicates that there is an increasing trend in incidence in all cell types
      of lymphomas, in both sexes. To obtain the details of the risk factors of these
      malignancies, more analytic epidemiological studies have to be undertaken of the
      Indian data and more importance given to lymphomas in the early detection and
      control of cancer.

PMID- 9538192
TI  - Proteasomes: structure and biology.
AB  - The proteasome is a multisubunit protease complex with an apparent sedimentation
      coefficient of 20S. Two types of regulatory complexes, named PA700 and PA28, bind
      to both ends of the cylindrical 20S proteasome to form the dumbbell-like and
      football-like proteasomes, respectively. The former complex, named the 26S
      proteasome, is a eukaryotic ATP-dependent protease and appears to be well
      organized as a large complex of 2 MDa, consisting of approximately 40
      polypeptides, to facilitate rapid proteolysis. It is assumed to be a protein
      "death machine", destroying a variety of cellular proteins that have acquired a
      specific degradation signal(s) such as a multiubiquitin chain. Recently data on
      in vivo substrates for the ubiquitin-proteasome pathway have been accumulating
      rapidly, implying its involvement in many biologically important processes, such
      as cell-cycle regulation, signal transduction, protein quality control, and the
      immune response. The newly-identified PA28 family proteins are inducible by
      interferons, and may cooperate with the 26S proteasome or play additional roles.
      Since the proteasome is capable of catalyzing breakdown of proteins not only
      irreversibly, but also rapidly and timely, it is thought to be a new regulatory
      system for biological reactions in eukaryotes.

PMID- 9538193
TI  - ATP-mediated activation of Ca2+-independent phospholipase A2 in secretory
      granular membranes from rat parotid gland.
AB  - We characterized the Ca2+-independent, membrane-associated phospholipase A2
      (PLA2) from rat parotid secretory granules. Among four phosphatidylcholine
      species with different fatty acyl (palmitoyl, oleoyl, linoleoyl, and
      arachidonoyl) groups at the sn-2 position, 2-arachidonoyl-phosphatidylcholine was
      the preferred substrate. Such specificity was also apparent even when 2
      arachidonoyl-phosphatidylcholine coexisted with another species. The various well
      documented inhibitors of PLA2s, bromoenol lactone, arachidonyl trifluoromethyl
      ketone, methyl arachidonyl fluorophosphate, and diisopropyl fluorophosphate, did
      not inhibit granular PLA2 activity. The granular PLA2 was activated markedly by
      ATP, and to a lesser extent by GTP and ATPgammaS. GTP also partially suppressed
      the ATP-mediated activation. UTP, CTP, GTPgammaS, and the hydrolyzed products of
      ATP and GTP showed little activation of the enzyme. Neither addition of K-252a
      nor depletion of Mg2+ affected ATP-mediated activation. Although this enzyme was
      located in the granular membranes, the granular soluble contents or BSA were
      required for the full activity and full ATP-mediated activation. These results
      suggested that the PLA2 located in granular membranes may participate in the
      liberation of arachidonic acid in parotid cells and be regulated through a
      mechanism mediated by ATP.

PMID- 9538194
TI  - Protective effect of linoleic acid on IFN gamma-induced cellular injury in
      primary culture hepatocytes.
AB  - We have previously demonstrated that treatment of hepatocytes with IFN gamma
      results a series of cellular injury processes, including DNA synthesis arrest,
      membrane breakage and apoptosis. In the present work, we show that IFN gamma
      suppresses cellular respiration and protein synthesis in hepatocytes, and that
      cellular respiration suppression is an early event in the IFN gamma-induced
      cellular injuries. Polyunsaturated fatty acids (PUFAs) increased cellular
      respiration of hepatocytes, but only linoleic acid showed some protective effect
      against IFN gamma-induced cellular respiration suppression. Linoleic acid also
      reduced other IFN gamma-mediated cellular injuries, including membrane breakage
      and protein synthesis inhibition. Like linoleic acid, fetal bovine serum also
      inhibited IFN gamma-induced cellular damage. Increased NAD levels were found in
      both IFN gamma-treated and non-treated hepatocytes following the addition of
      PUFAs, but clofibrate, a peroxisome proliferator, bromophenacyl bromide (BPB), an
      inhibitor of phospholipase, nordihydroguaiaretic acid (NDGA), an inhibitor of
      lipoxygenase, and arachidonic acid, a metabolite of linoleic acid, did not
      inhibit IFN gamma-induced cellular injury. In addition, the combination of
      linoleic acid and IFN gamma induced nitric oxide (NO) synthesis in hepatocytes.
      These results suggest that fatty acid may play an important role in liver
      homeostasis during chronic inflammatory states and sepsis.

PMID- 9538195
TI  - Purification and some characteristics of phosphatase of a psychrophile.
AB  - The phosphatase of a psychrophile was purified by ammonium sulfate fractionation,
      and a sequence of chromatographies on DEAE-Cellulofine, butyl-Cellulofine,
      Sephacryl S-100, and Mono-Q columns. The purified enzyme preparation was found to
      be electrophoretically homogeneous on native- and SDS-PAGE, and its molecular
      mass was determined to be 38.4 kDa by MALDI-TOF mass spectrometry. Maximal
      activity was observed at 30 degrees C and pH 6.0. Furthermore, the activity of
      this enzyme at 0 and 5 degrees C was 27 and 28%, respectively, of that at 30
      degrees C. The enzyme was stable in the pH range of 6.0 to 8.0 and up to 20
      degrees C. The enzyme was affected by metal ions; the activity was enhanced by
      Mg2+ and Ca2+ ions, but depressed by Zn2+ ions. Analysis of the amino acid
      composition indicated that this phosphatase contains no S-S bond, and only a few
      prolyl residues necessary to retain the rigid structure of a protein molecule.
      The phosphatase shows typical features of a cold enzyme; high catalytic activity
      at low temperature and rapid inactivation at an intermediate temperature.

PMID- 9538196
TI  - Suppression of thermotolerance development through cycloheximide-induced negative
      control of stress protein gene expression.
AB  - Expression of a luciferase reporter gene by Chinese hamster ovary cells under the
      control of the human heat shock protein (hsp) 70 gene promoter was suppressed by
      incubation at 37 degrees C after treatment with cycloheximide (CHX) during 42
      degrees C heat shock exposure. The CHX-induced suppression of hsp gene expression
      induced no development of thermotolerance. However, 42 degrees C heat shock
      treatment without CHX followed by CHX inhibition of protein synthesis during
      recovery incubation at 37 degrees C induced thermotolerance expression by
      inducing enhanced synthesis of hsps including hsp70 in subsequent heat challenge
      incubation at 43 degrees C. The results demonstrated a direct correlation between
      suppression (induction) of stress protein gene expression and non-expression
      (expression) of thermotolerance. Kinetic analysis showed that the CHX suppression
      of hsp gene induction was greater than the CHX inhibition of protein synthesis,
      and that it depended on the severity of heat stress: it decreased with increasing
      heat stress doses. Moreover, prior feeding of the proline analog L-azetidine 2
      carboxylic acid abrogated the CHX-induced suppression of hsp gene expression. In
      addition, CHX treatment during heat cell-killing at 43 degrees C induced
      protection of cells. These results were well explained by the proposed model of
      negative or positive control of stress protein gene expression depending on the
      level of free hsp70, which may be modulated by both the rate of protein synthesis
      and the severity of heat stress.

PMID- 9538197
TI  - Hypotonically loaded rat erythrocytes deliver encapsulated substances into
      peritoneal macrophages.
AB  - Previous work has shown increased uptake of hypotonically loaded rat RBCs by the
      spleen and liver "in vivo," suggesting that the cells of MPS are involved in
      their elimination from the circulation. In order to elucidate the mechanism of
      such elimination, we have undertaken studies on the interaction of such loaded
      RBCs, in comparison with native RBCs, with peritoneal macrophages.
      Erythrophagocytosis assays were performed in well plates to which thioglycollate
      induced peritoneal macrophages had adhered. Native or loaded 51Cr-RBCs were added
      under different opsonization conditions to monolayer adherent macrophages, and
      then the amount of RBCs that were recognized was determined, with separation into
      adhesion and phagocytosis fractions. Native RBCs are slightly recognized by
      peritoneal macrophages, about one RBC per macrophage (Mphi). Osmotic treatment of
      rat RBCs used for encapsulation (independently of the encapsulated substance,
      125I-CA or FITC-dextran) produces some modification in the erythrocyte membrane
      that induces higher recognition of these cells, about three loaded RBCs per
      macrophage. Consequently, both fluorescent (FITC-Dx) and radioactive (125I-CA)
      substances previously encapsulated in RBCs were transferred to M(phi)s. The
      fluorescence microscopic observations confirmed these results. Moreover, in the
      case of carrier 51Cr-cells loaded with 125I-CA, the amount of 125I-radioactivity
      delivered into M(phi)s was relatively higher than that of 51Cr. The highest
      ratio, 125I-CA (encapsulated substance)/51Cr-RBCs (carrier cells), present in
      M(phi)s means there was a stronger interaction with macrophages of RBCs that
      carry a higher amount of encapsulated CA, as a function of the heterogeneity of
      the loaded rat RBCs population previously reported. Finally, the adhesion and
      phagocytosis of loaded RBCs seem not to involve complement receptors or Fc
      receptors on the macrophages.

PMID- 9538198
TI  - Disaccharide analysis of heparin and heparan sulfate using deaminative cleavage
      with nitrous acid and subsequent labeling with paranitrophenyl hydrazine.
AB  - Compositional analyses of heparin (Hep) and heparan sulfate (HS) have been
      undertaken with disaccharide units obtained by either enzymatic digestion with
      heparitinases or hydrazinolysis/deamination reaction of polysaccharides.
      Unsaturated disaccharide units generated by the enzymatic method are detectable
      on HPLC with a uv detector recording absorbance at 230 nm. On the other hand,
      disaccharide units generated by the chemical method possess a component of 2,5
      anhydromannose (AnMan) bearing aldehyde groups in addition to intact iduronic
      acid (IdoA) or glucuronic acid (GlcA). The aldehyde groups of the disaccharide
      units are usually reduced with sodium borotritide, and detected by
      radiochromatography. Both of them, however, involve inevitable experimental
      problems, such as the use of costly enzymes and radioisotopes. In the present
      study, we have established a novel composition analysis system for Hep and HS
      essentially based on the chemical method. After hydrazinolysis/deamination
      treatment of Hep and HS, the aldehyde groups of AnMan in the disaccharide units
      generated were coupled with paranitrophenyl (PNP-) hydrazine instead of reduction
      with sodium borotritide, AnMan-CH=N-NH-PNP (AnMan-PNP) being formed. Then, the
      PNP-labeled disaccharides were pre-treated on a SepPak C-18 cartridge column, and
      subsequently separated and detected on ion-pairing reversed-phase HPLC with a
      detector recording absorbance at 390 nm. With the present system, the order of
      elution was GlcA-AnMan-PNP (GM), IdoA-AnMan-PNP (IM), IdoA(2S)-AnMan-PNP (ISM),
      IdoA-AnMan(6S)-PNP (IMS), and IdoA(2S)-AnMan(6S)-PNP (ISMS). As an application,
      the disaccharide compositions of heparin from bovine intestine and heparan
      sulfate from bovine kidney were analyzed by the present method, and the results
      were comparable to those obtained by a well-established enzymatic method. The
      present compositional analysis was demonstrated to be reliable and economical.

PMID- 9538199
TI  - Purification and characterization of a puromycin-hydrolyzing enzyme from
      blasticidin S-producing Streptomyces morookaensis.
AB  - Blasticidin S-producing Streptomyces morookaensis JCM4673 produces an enzyme
      which inactivates puromycin (PM) by hydrolyzing an amide linkage between its
      aminonucleoside and O-methyl-L-tyrosine moieties [Nishimura et al. (1995) FEMS
      Microbiol. Lett. 132, 95-100]. In this study, we purified to homogeneity the
      enzyme from the cell-free extracts of S. morookaensis. The molecular weight of PM
      hydrolyzing enzyme, estimated by SDS-PAGE and gel filtration, was 68 and 66 kDa,
      respectively, suggesting that this protein is monomeric. The PM-hydrolyzing
      activity was strongly inhibited by Zn2+, Fe2+, Cu2+, Hg2+, and N
      bromosuccinimide, but was stimulated by DTT. The optimum pH and temperature for
      PM-hydrolyzing activity were 8.0 and 45 degrees C, respectively. Several L
      aminoacyl-beta-naphthylamides were good substrates for the enzyme, suggesting
      that the PM-inactivating enzyme has an aminopeptidase activity. The N-terminal
      sequence of the first 14 amino acids (Val-Ser-Thr-Ala-Pro-Tyr-Gly-Ala-Trp-Gln-Ser
      Pro-Ile-Asp) of the enzyme showed no significant homology with any published
      hydrolase sequences.

PMID- 9538200
TI  - L-kynurenine 3-monooxygenase from mitochondrial outer membrane of pig liver:
      purification, some properties, and monoclonal antibodies directed to the enzyme.
AB  - We have purified L-kynurenine 3-monooxygenase from pig liver mitochondria using a
      procedure involving seven steps composed of (1) preparation of mitochondrial
      outer membrane, (2) preparation of the zwitterionic detergent, 3-[(3
      cholamidopropyl)dimethylammonio]-1-propane sulfonate (Chaps) insoluble outer
      membrane material, (3) extraction of the enzyme with beta-octylglucoside, (4)
      ammonium sulfate fractionation, (5) DEAE-Sepharose CL-6B chromatography, (6)
      Matrex gel orange A affinity chromatography, and (7) high-performance liquid
      chromatography (HPLC) gel filtration. The final preparation had an about 160-fold
      purified enzyme activity with a yield of 0.8%. The apparent molecular mass of the
      aggregated form of the native enzyme was determined to be close to 300 kDa by
      HPLC gel filtration in the presence of 0.005% Triton X-100. Sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) showed a main protein band
      with an apparent molecular mass of about 49 kDa. The enzyme was found to be about
      86% pure by the criterion of SDS-PAGE. The dissociated form of the enzyme
      contains 1 mol of non-covalently bound FAD/mol of protein monomer. The UV/visible
      spectrum had absorption peaks at 275, 384, and 450 nm, typical of a simple
      flavoprotein. Five inhibitory monoclonal antibodies against the enzyme were
      obtained. They could stain moderately a single protein band (49 kDa) in a Western
      blot.

PMID- 9538201
TI  - Quantification of sphingosine derivatives in human platelets: inducible formation
      of free sphingosine.
AB  - To elucidate the physiologic role of sphingolipid-derived products as signaling
      molecules, we analyzed the levels of endogenous sphingosine (Sph) derivatives in
      human platelets. When the platelets were stimulated with thrombin or 12-O
      tetradecanoylphorbol 13-acetate, neither ceramide formation nor sphingomyelin
      hydrolysis was observed, which suggests that the sphingomyelin cycle may not be
      an essential part of the signaling pathway under these conditions. In contrast,
      Sph was found to increase in platelets upon stimulation. The level of Sph 1
      phosphate, which is formed from Sph by the action of Sph kinase, was not affected
      under our conditions. Although it has been established that Sph inhibits protein
      kinase C, which regulates the functional responses of the platelets, Sph levels
      which exert an inhibitory effect on protein kinase C cannot be attained under
      physiological conditions (without exogenous Sph). Considering the stimulation of
      the synthesis of Sph by the physiological agonist thrombin, we speculate that Sph
      is a signaling molecule of physiological importance in platelets, but protein
      kinase C may not be its target.

PMID- 9538202
TI  - Temperature effects on the structural and functional properties of GPI-anchored
      and anchor-less bull seminal plasma ecto-5'-nucleotidase.
AB  - The effects of temperature on the three-dimensional organization and on the
      secondary structure of GPI-anchored 5'-nucleotidase from bull seminal plasma and
      of its anchor-less form (solubilized ecto-5'-nucleotidase), obtained after GPI
      anchor removal by phosphatidylinositol-specific phospholipase C were investigated
      in parallel by circular dichroism and fluorescence spectroscopy. The structural
      features of the two enzymes were correlated to their functional properties in the
      temperature range of 25-90 degrees C. The kinetic data indicated that the enzyme
      activities were temperature dependent, showing the maximal values at 60 degrees
      C. The relevant Arrhenius plots were linear in the temperature range of 20-60
      degrees C and the activation energies were 44.4 and 51.8 kJ/mol for the
      solubilized and GPI-anchored 5'-nucleotidase, respectively. The time-course
      measurements of enzyme activity, in the temperature range of 25-55 degrees C,
      revealed that the two enzymes were of different thermal stability, the
      solubilized ectoenzyme showing lower thermal deactivation constants and longer
      half lives. Fluorescence and near UV circular dichroism spectroscopy showed that
      temperature increases induced remarkable changes in the protein tertiary
      structure of the two enzymes, whereas far-UV circular dichroism analysis revealed
      only a small temperature effect on the protein secondary structure content.

PMID- 9538203
TI  - Conversion of neopullulanase-alpha-amylase from Thermoactinomyces vulgaris R-47
      into an amylopullulanse-type enzyme.
AB  - TVA I, an alpha-amylase from Thermoactinomyces vulgaris R-47, is a versatile
      enzyme which hydrolyzes the alpha-(1-->4)-glucosidic linkages of pullulan to
      produce panose, known as neopullulanase activity, and the alpha-(1-->6)
      glucosidic linkages of certain oligosaccharides. We modified the Ala-357, Gln
      359, and Tyr-360 residues located in region II, one of the four regions conserved
      in alpha-amylase family enzymes, and deleted 11 consecutive amino acid residues
      located after the C-terminus of region II of the TVA I sequence by means of site
      directed mutagenesis. The action pattern of the mutated enzyme for pullulan was
      greatly altered and it hydrolyzed mainly the alpha-(1-->6)-glucosidic linkages of
      pullulan to produce maltotriose, while the action patterns for starch and
      maltooligosaccharides were almost identical to those of the wild-type enzyme.
      This means that the mutated TVA I has lost the neopullulanase activity, and thus
      can be designated as an amylopullulanase-type enzyme. The kcat/Km value of the
      mutated enzyme for alpha-(1-->6)-glucosidic linkages was virtually unaltered,
      while that for alpha-(1-->4)-glucosidic linkages was about 100 times smaller than
      that of the wild-type enzyme.

PMID- 9538205
TI  - Differential scanning calorimetric studies on the thermal unfolding of
      Pseudomonas cepacia lipase in the absence and presence of alcohols.
AB  - Thermal unfolding of Pseudomonas cepacia lipase (PCL) was studied by differential
      scanning calorimetry (DSC) at pH 7. The peak temperature tp of the DSC trace
      increased with increasing concentration of the protein. The DSC traces could be
      successfully analyzed on the basis of the following mechanism, assuming the
      dissociation of a calcium ion upon denaturation; N Ca2+<-->D + Ca2+, where N and
      D represent native and denatured states of PCL, respectively. In the presence of
      1-5% alcohols (methanol, ethanol, n-propanol, and n-butanol), tp decreased with
      increasing alcohol concentration and longer alkyl chain. In contrast to the case
      of tp, the denaturation enthalpy deltah did not depend on the protein
      concentration or alcohol concentration used. The change in heat capacity on
      denaturation, deltacp(d), evaluated directly from the DSC traces, was close to
      zero both in the absence or presence of alcohol, which could be due to the open
      conformation of the enzyme exposing a large hydrophobic surface to the solvent.

PMID- 9538204
TI  - Characterization of heparinase from an oral bacterium Prevotella heparinolytica.
AB  - Heparinase was purified to homogeneity from the cell extract of an oral
      bacterium, Prevotella heparinolytica, by a combination of anion exchange
      chromatography, gel filtration chromatography, and hydroxyapatite chromatography.
      Properties of the purified P. heparinolytica heparinase (P. heparinase) were
      investigated. The enzyme exhibited a maximum activity in 50 mM Tris-HCl buffer,
      pH 7.5-8.0, containing 75 mM sodium acetate, 0.1 M NaCl, and 1 mM CaCl2. Optimum
      conditions for the maximum activity of P. heparinase were similar to those of the
      heparinase from Flavobacterium heparinum (F. heparinase). The two enzymes also
      yielded similar digestion profiles of various glycosaminoglycans and heparin
      tetrasaccharides, suggesting that they have a similar substrate specificity.
      Kinetic study of the P. heparinase reaction using porcine intestinal heparin as
      substrate gave a Km value of 3.8 x 10(-5) M and a Vmax value of 11.4 micromol/min
      x mg protein. The Michaelis constant of P. heparinase was slightly larger than
      but not significantly different from that of F. heparinase. The amino acid
      composition of P. heparinase was also similar to that of F. heparinase, but its N
      terminal sequence of 20 amino acid residues was different and hitherto
      unreported. These results together indicate that these heparinases are different
      proteins with closely similar enzymatic properties. Since F. heparinum produces
      not only heparinase but also heparitinase II, which has a broad substrate
      specificity, F. heparinase may be contaminated with this enzyme. In contrast, P.
      heparinolytica does not produce heparitinase II, and P. heparinase should prove a
      useful tool for degrading heparin without the risk of contamination with
      heparitinase II.

PMID- 9538206
TI  - ATPase associated with ribosomal 30S-5SRNP particles and 40S subunits of rat
      liver.
AB  - The ATPase activity of rat liver 30S-5SRNP particles prepared by EDTA treatment
      of 80S ribosomes, and that of 40S subunits were investigated in correlation with
      polypeptide elongation. The ATPase activity of 30S-5SRNP particles was higher
      than that of 40S subunits. Poly(U) and TMV RNA stimulated the ATPase activity of
      30S-5SRNP particles more markedly than that of 40S subunits. These two kinds of
      particles also showed intrinsic GTPase. Poly(U) enhanced the GTPase activity of
      30S-5SRNP particles but not that of 40S subunits. An elongation factor (EF
      1alpha, EF-2, or EF-1alphabetagamma) alone or in combination with poly(U) and/or
      other elongation factors stimulated the ATPase activities of both particles. The
      extent of stimulation of the ATPase activity by a combination of these components
      was usually somewhat higher than or similar to the sum of those with the
      individual components. The extents of stimulation by these components were higher
      in the case of 30S-5SRNP particles than that of 40S subunits, indicating the
      importance of the 5SRNP moiety in the former particles. The intactness of 18SrRNA
      was required for promotion of the ATPase activity of 30S-5SRNP particles by
      Phe(+), (-)tRNA(Phe). The ATPase activities of the two kinds of particles by
      themselves or those observed with the combinations of the components mentioned
      above were inhibited by several kinds of translation inhibitors. The degrees of
      inhibition were generally higher for 30S-5SRNP particles. The ATPase activity of
      40S subunits was enhanced by spermidine, suggesting the importance of the
      conformational change induced by it. These results imply the participation of the
      intrinsic ATPase of 30S-5SRNP particles and 40S subunits in polypeptide
      elongation, and the important role of the 5SRNP moiety of 30S-5SRNP particles in
      the ATPase activity.

PMID- 9538208
TI  - Detection of a local interaction of hen lysozyme under highly denaturing
      conditions using chemically 13C-enriched methionine resonance.
AB  - Using hen lysozyme in which the epsilon-carbons of two methionine residues are
      enriched with 13C nuclei, we found that there is a subtle difference in the
      chemical shift of the epsilon-carbon resonances between Met 12 and Met 105 in
      thermally denatured lysozyme without any reduction of disulfide bonds at pD 3.8,
      and also in reduced S-alkylated lysozyme at pD 3.8 and 35 degrees C. The
      difference in the chemical shift was abolished on digestion with TPCK-trypsin and
      the chemical shifts of both resonances converged to that of Met 12, whose
      chemical shift is identical to that in the randomly coiled state. Therefore, it
      is suggested that the chemical shift in the epsilon-carbon resonance of Met 105
      is different from that in the randomly coiled state due to an interaction
      involving Met 105. In order to locate the interaction involving Met 105,
      fragmentation of the reduced S-alkylated lysozyme into the peptides was carried
      out by means of chemical cleavage or specific endoprotease digestion. As a
      result, the local interaction of Met 105 or the residues around Met 105 with
      eleven residues at the C-terminus of lysozyme is suggested to occur.

PMID- 9538207
TI  - Biochemical and functional properties of lysine-specific cysteine proteinase (Lys
      gingipain) as a virulence factor of Porphyromonas gingivalis in periodontal
      disease.
AB  - The oral anaerobic bacterium Porphyromonas gingivalis has been implicated as a
      major etiologic agent of progressive periodontal disease. A novel lysine-specific
      cysteine proteinase, termed "Lys-gingipain," was purified from the culture
      supernatant of the Arg-gingipain-deficient mutant of P. gingivalis (KDP112) by a
      simple method including immunoaffinity chromatography. The purified enzyme was
      found to be composed of a single polypeptide of Mr=51,000. Analysis of the
      enzymatic properties revealed several distinctive features of this enzyme. The
      proteolytic activity was remarkably activated by thiol-reducing agents and
      inhibited by idoacetamide, idoacetic acid, and leupeptin. The enzyme was also
      inhibited by the chloromethyl ketones of tosyl-L-lysine and tosyl-L
      phenylalanine. However, internal protease inhibitors, such as cystatins and
      alpha1-antichymotrypsin, had no effect on the activity, suggesting its resistance
      to normal host defense systems in vivo. Despite its narrow specificity for
      synthetic substrates containing Lys in the P1 site, the enzyme extensively
      degraded human type I collagen and immunoglobulins G and A (both serum and
      secretory types). Most important, the enzyme was able to disrupt the functions of
      polymorphonuclear leukocytes, as shown by its inhibitory effect on the generation
      of active oxygen species from the activated cells. These results suggest that Lys
      gingipain, like Arg-gingipain, plays a crucial role as a virulence factor from P.
      gingivalis in the development of periodontal disease via the direct destruction
      of periodontal tissue components and the disruption of normal host defense
      mechanisms.

PMID- 9538209
TI  - Coexistence of both oleosin isoforms on the surface of seed oil bodies and their
      individual stabilization to the organelles.
AB  - The oil bodies of plant seeds contain a triacylglycerol matrix surrounded by a
      monolayer of phospholipids embedded with alkaline proteins termed oleosins. Two
      distinct oleosin isoforms with molecular masses of 18 and 16 kDa are present in
      rice oil bodies. Chicken antibodies raised against oleosin 18 kDa and rabbit
      antibodies raised against oleosin 16 kDa did not cross-recognize these two
      homologous isoforms. This peculiar non-cross recognition was used to locate the
      two oleosin isoforms on the surface of oil bodies via immunofluorescence
      detection using anti-chicken IgG conjugated with FITC (fluorescein
      isothiocyanate) and anti-rabbit IgG conjugated with Texas-Red. The results
      revealed that both oleosin isoforms resided on each oil body in vivo and in
      vitro. Artificial oil bodies were reconstituted via sonication using
      triacylglycerol, phospholipid, and oleosins. The results indicated that the two
      rice oleosin isoforms could stabilize artificial oil bodies individually whereas
      oleosin 16 kDa provided better stability to the organelles than oleosin 18 kDa.

PMID- 9538210
TI  - Ca2+-induced distance change between points on actin and troponin in skeletal
      muscle thin filaments estimated by fluorescence energy transfer spectroscopy.
AB  - Fluorescence resonance energy transfer spectroscopy has been used to study the
      spatial relationships between probes attached to actin and troponin in the
      reconstituted skeletal muscle thin filament in the presence and absence of Ca2+
      ions. Gln-41 and the nucleotide-binding site of actin were selectively labeled
      with the acceptor probe: fluorescein cadaverine and 2'(or 3')-O-(2,4,6
      trinitrophenyl)adenosine 5'-diphosphate (TNP-ADP), respectively. Troponin was
      selectively labeled at positions 9 or 133 of troponin-I and 98 of troponin-C with
      a donor probe; 5-(2-iodoacetylaminoethyl)aminonaphthalene 1-sulfonic acid
      (IAEDANS). The distances between probes attached to position 133 of TnI and Gln
      41 or the nucleotide site of actin were determined to be 51.6+/-1.2 and 42.7+/
      0.9 A respectively in the presence of Ca2+, and these distances decreased by 11.5
      and 9.3 A respectively in the absence of Ca2+ ions. The distances between the
      probes attached to position 9 of TnI and Gln-41 or the nucleotide site of actin
      were determined to be 59.1+/-2.0 or 49.3+/-1.5 A respectively in the presence of
      Ca2+, and the distances decreased by 5.3 or 3.7 A in the absence of Ca2+. The
      distances between probes attached to position 98 of TnC and Gln-41 or the
      nucleotide site of actin were determined to be 55.1+/-1.7 and 57+/-5 A in the
      presence of Ca2+ and the distances increased slightly by approximately 1 A in the
      absence of Ca2+. The results suggest that the C-terminal domain of troponin I
      moves to the outer domain of actin during inhibition, while the C-terminal domain
      of TnC does not move much.

PMID- 9538211
TI  - Identification and characterization of porcine NP-190, a novel protein that is
      specifically expressed in the axonal membrane during the embryonic period.
AB  - To identify and analyze the function of proteins expressed in the growth cones,
      we have screened monoclonal antibodies raised against the preparation of the
      growth cone particles derived from fetal porcine brains and found a novel
      neuronal antigen, termed NP-190. Biochemical characterization of NP-190
      demonstrated that it was an integral membrane protein with an apparent molecular
      weight of 190 kDa and that it was mainly expressed in fetal brains. Homologous
      antigens with molecular weights of 200 and 170 kDa were also identified in the
      fetal brain extracts of chickens and rats, respectively. Immunoblot experiments
      of brain extracts from chickens and rats in various stages of development
      indicated that the expression of NP-190 homologs was developmentally regulated;
      it began to appear and increased in the embryonic stage, then decreased to very
      low level in the adult brains. Immunostaining of cultured primary of neurons from
      the embryonic day 18 rat cerebral cortex demonstrated that rat NP-190 homolog
      localized in the cell bodies, axons and growth cones, but not in dendrites.
      Partial amino acid sequence analysis of affinity-purified NP-190 from fetal
      porcine brains demonstrated that it was a novel protein. These results suggest
      that NP-190 plays a distinct role in brain development.

PMID- 9538212
TI  - Midkine counteracts the activin signal in mesoderm induction and promotes neural
      formation.
AB  - Midkine (MK) is a heparin-binding growth factor that has been implicated in
      neural survival and differentiation, fibrinolysis, and carcinogenesis. It is
      expressed in the nervous system during early Xenopus development. In the present
      study, we demonstrated that injection of vegetal blastomeres with Xenopus MK at
      the 8-cell stage results in incomplete invagination. In the case of dorsal
      vegetal injection, hypertrophic neural tissue is produced. Animal caps isolated
      from embryos that have been injected with Xenopus MK and cultured with activin do
      not elongate, and all mesoderm markers examined, including both head and
      trunk/tail ones, are greatly diminished. In contrast, head-specific neural
      markers, XANF-1 and Xotx2, are induced, while trunk/tail neural markers, XlHbox6
      and F-spondin, are decreased. Moreover, MK showes the same effects in animal caps
      injected with Xenopus Smad2 mRNA.

PMID- 9538213
TI  - Thiolase involved in bile acid formation.
AB  - The formation of cholic acid and chenodeoxycholic acid through cleavage of the
      side chains of CoA esters of 3alpha,7alpha,12alpha-trihydroxy-5beta-choles tan-26
      oic acid and 3alpha,7alpha-dihydroxy-5beta-cholestan-26-oic acid is believed to
      occur in peroxisomes. Recently, we found a new peroxisomal enzyme, D-3
      hydroxyacyl-CoA dehydratase/D-3-hydroxyacyl-CoA dehydrogenase bifunctional
      protein, and suggested that this bifunctional protein is responsible for the
      conversion of 3alpha,7alpha,12alpha-trihydroxy-5beta-cholest-2 4-en-26-oyl-CoA
      and 3alpha,7alpha-dihydroxy-5beta-cholest-24-en-26-oyl-CoA to their 24-oxo-forms.
      In the present study, the products of this bifunctional protein reaction were
      analyzed by gas chromatography-mass spectrometry, and the formation of 24-oxo-27
      nor-cholestanes was confirmed. Previously, we found a new thiolase in
      Caenorhabditis elegans, P-44, and suggested that P-44 and sterol carrier protein
      x, a peroxisomal protein, constitute a second group of 3-oxoacyl-CoA thiolases.
      The production of cholic acid and chenodeoxycholic acid from the precursors on
      incubation with the bifunctional protein and sterol carrier protein x or P-44 was
      confirmed by gas chromatography.

PMID- 9538214
TI  - Overexpression of aldehyde reductase protects PC12 cells from the cytotoxicity of
      methylglyoxal or 3-deoxyglucosone.
AB  - The glycation reaction (Maillard reaction) plays a major role in diabetic
      complications, since some reaction intermediates are responsible for the
      modification and cross-linking of long-lived proteins, resulting, in turn, in a
      deterioration of normal cell function. The reaction intermediates include
      methylglyoxal (MG) and 3-deoxyglucosone (3-DG), both of which are cytotoxic
      dicarbonyl compounds and are elevated during hyperglycemia. Aldehyde reductase
      (ALR) catalyzes the reduction of both compounds. To examine the intracellular
      role of ALR in the diabetic complications of neural cells, its gene was
      overexpressed in rat pheochromocytoma PC12 cells, which normally express a low
      level of ALR. Western blot analysis showed that ALR protein in the ALR gene
      transfected cells was more than twice as much as in the control cells. In the
      parental cells, cytotoxicity, including apoptotic cell death, which was
      determined by fluorescent microscopy using the fluorescent DNA binding dye
      Hoechst 33258, was observed at 100 microM MG. In the ALR gene-transfected cells,
      the cytotoxicity of both MG and 3-DG and apoptotic cell death were decreased.
      This suggests that intracellular ALR protects neural cells from the cytotoxicity
      of 3-DG or MG, and that neural cells, which normally express a low level of ALR,
      might be susceptible to diabetic complications caused by intermediate products of
      the Maillard reaction, such as 3-DG and MG.

PMID- 9538215
TI  - Genomic structures and chromosomal location of p91, a novel murine regulatory
      receptor family.
AB  - Recently, we found a novel murine cell-surface glycoprotein, designated as p91,
      expressed mainly in myeloid cells such as macrophages and mast cells. The
      molecule has six immunoglobulin-like extracellular domains, a transmembrane
      segment, and a cytoplasmic tail containing four immunoreceptor tyrosine-based
      inhibition motif (ITIM) or ITIM-like sequences, resembling the structural
      features of human killer-cell inhibitory receptors (KIR). Here we show that p91
      comprises a polymorphic gene family, harboring one potent inhibitory-type p91 and
      at least two other p91 genes. Tyrosine-phosphorylated, but not nonphosphorylated,
      synthetic peptides matching the third ITIM and the fourth ITIM-like sequences,
      respectively, found in the cytoplasmic portion of p91A, the sole inhibitory-type
      p91, were associated with the tyrosine phosphatases, SHP-1 and SHP-2. In
      addition, the phosphotyrosyl peptide matching the third ITIM sequence also bound
      the inositol 5-phosphatase, SHIP. These results support the notion that p91A may
      function as an inhibitory cell-surface molecule against cell activation. The p91
      genes were shown to be clustered in the proximal region of mouse chromosome 7, a
      syntenic position of human chromosome 19 where the genes for the KIR family are
      found. A human cDNA clone cross-hybridizing to a murine p91 probe was isolated
      from a human spleen cDNA library, and was found to code for a molecule quite
      similar to members of the immunoglobulin-like transcript (or ILT) family. The
      gene was found to be located on human chromosome 19q13.3-13.4. These results
      establish the existence of a novel set of potent regulatory receptors in mouse
      and man, similar but different from the KIR family.

PMID- 9538216
TI  - Structure and function of bacterial cytochrome c oxidase.
AB  - The crystal structure of cytochrome c oxidase from the soil bacterium Paracoccus
      denitrificans has been reported. This structure has provided a basis for
      understanding the mechanism of the redox-coupled transmembrane proton pump which
      is the key component of the respiratory chain in most aerobic organism. Over the
      past ten years, there have been many site-directed mutagenesis studies performed
      on bacterial oxidases. Structural features of Paracoccus oxidase have been
      summarized in the light of these mutagenesis studies and other structural works.

PMID- 9538217
TI  - Ablation of Nrf2 function does not increase the erythroid or megakaryocytic cell
      lineage dysfunction caused by p45 NF-E2 gene disruption.
AB  - Maf recognition elements (MAREs or NF-E2 binding sites) have been shown to be
      vital for erythroid- and megakaryocyte-specific gene expression. Transcription
      factor NF-E2 is composed of p45, a large subunit belonging to the CNC family
      proteins, and a small Maf subunit, and is thought to activate transcription
      through its binding to MAREs in both the erythroid and megakaryocytic cell
      lineages. While p45 gene knockout mice exhibit thrombocytopenia due to abnormal
      terminal differentiation of megakaryocytes, and the mutant mice die of massive
      bleeding within a week after birth, anemia is not apparent in these animals.
      Disruption of the nrf2 gene, encoding another CNC family protein, results in no
      hematological abnormalities. We have therefore tested the hypothesis that Nrf2
      might compensate for the p45 deficiency in erythroid lineage cells of p45
      knockout mice, thereby masking the anticipated anemia. However, we failed to
      detect any greater failure in either erythroid or megakaryocytic cell development
      in Nrf2 plus p45 compound mutant mice as compared to with either individual
      homozygous mutation. These data suggest that p45 and Nrf2 may both be dispensable
      for hematopoietic cell development, and that other factors regulate erythroid-
      and megakaryocyte-specific gene expression through their required MAREs.

PMID- 9538218
TI  - Properties of the proteolytically generated catalytic domain (42 kDa kinase) of
      epidermal growth factor receptor: comparison with holoenzyme.
AB  - Treatment of A431 cell membranes with trypsin or Streptomyces griseus proteinase
      results in degradation of the EGF-R and the concomitant generation of an active
      kinase with a molecular mass of 42 kDa (42 kDa kinase). To investigate the
      biochemical properties of the 42 kDa kinase, the EGF-R was immunoaffinity
      purified from the A431 cell membranes and the kinase proteolytically generated.
      The proteolysis of EGF-R changes both the Vmax and the Michaelis constants of
      substrates. These substrates determine the extent of the changes of the
      parameters. The 42 kDa kinase is less responsive to polyions as regulators of
      kinase activity and is less efficiently inhibited by genistein and tyrphostin.
      The experiments described here point to a role of the extracatalytic domains in
      determining the substrate specificity and regulation of kinase activity.

PMID- 9538219
TI  - Genomic cloning of 18 kDa oleosin and detection of triacylglycerols and oleosin
      isoforms in maturing rice and postgerminative seedlings.
AB  - Oleosins are hydrophobic proteins localized abundantly in the oil bodies of plant
      seeds. Two distinct oleosin isoforms of molecular masses 18 and 16 kDa are
      present in rice oil bodies. These isoforms were found in similar ratio in rice
      embryos and aleurone layers. To survey potential DNA sequences involved in the
      activation of oleosin genes, a genomic clone of rice 18 kDa oleosin was
      sequenced, and its 5'-flanking region was compared with that of the known rice 16
      kDa oleosin gene. Corresponding mRNAs of the two rice oleosin isoforms appeared
      seven days after pollination and vanished in mature seeds. Triacylglycerols and
      oleosins were accumulated concomitantly in maturing rice reeds in accord with the
      active assembly of oil bodies, and partly mobilized in postgerminative seedlings.
      Approximately 60% of the stored triacylglycerols in rice were not utilized: while
      the majority of oil bodies in embryos were mobilized in five days after
      imbibition, those in aleurone layers remained intact in postgerminative
      seedlings.

PMID- 9538220
TI  - Detection, localization, and sequence analyses of mitochondrial regulatory region
      RNAs in several mammalian species.
AB  - The mitochondrial regulatory region (mrr) located between the tRNAPhe and tRNAPro
      genes of mitochondrial DNA (mtDNA) is essential for regulation of replication and
      transcription of the mitochondrial genome. Polyadenylated short RNAs
      complementary to the L-strand of the mrr in human cells and similar RNAs
      (polyadenylation status unknown) in rat and mouse cells have been reported. We
      now report detection of ca. 0.2 kb polyadenylated mrrRNAs in cultured cells of
      Chinese hamster, African green monkey, mouse, rat, and human. We isolated a cDNA
      clone to a rat polyadenylated mrrRNA of 158 bp in length excluding the polyadenyl
      tail, which spans the region from the light strand promoter (LSP) to the origin
      of heavy strand replication (OriH). This cDNA contains both an open reading frame
      encoding a 26 amino acid polypeptide and a 12 nucleotide sequence complementary
      to the 3'-terminus of rat mitochondrial 12S rRNA. A cDNA clone to a human HeLa
      cell polyadenylated mrrRNA also contains a 12 nucleotide region complementary to
      the human mitochondrial 12S rRNA. We used a mitochondrial genome-deficient HeLa
      cell line, rho0 HeLa, and a derived cybrid cell line, HeEB, with a reconstituted
      mitochondrial genome, to demonstrate that the occurrence of the mrrRNA is
      dependent on the presence of a mitochondrial genome, and these polyadenylated
      mrrRNAs are transcribed from the mitochondrial genome. Our results further
      substantiate the common existence of polyadenylated mrrRNAs among mammals and
      support previously proposed hypotheses for the multi-functional nature of
      polyadenylated mrrRNA.

PMID- 9538221
TI  - Developmental profiles of phosphorylated and unphosphorylated CREBs in murine
      calvarial MC3T3-E1 cells.
AB  - The cAMP-responsive element (CRE) binding protein/activating transcription factor
      (CREB/ATF) family plays a major role in the expression of skeletal-specific genes
      and skeletal tissue development. We analyzed the changes of the amount, degree of
      phosphorylation and binding activity of the CREB/ATF family in the course of
      development of the murine calvarial osteoblastic cell line MC3T3-E1 as an in
      vitro model system of bone formation. The amount of CREB in the whole-cell
      extract detectable by Western blot analysis was high through all stages of
      development and maximal in the proliferation stage. The degree of phosphorylation
      estimated with anti-phosphorylated CREB antibody changed greatly and reached high
      levels in the proliferation stage and early mineralization stage. The ratio of
      phosphorylated CREB to total CREB in the CREB-CRE complex was also examined by
      gel shift assay. Although the binding to the consensus/CRE probe reached almost
      equally high levels in the proliferation stage and early mineralization stage,
      the relative level of phosphorylated CREB in the CREB-CRE complex was different
      in these two stages. In the early mineralization stage, most CREB bound to
      consensus/CRE was phosphorylated, while both phosphorylated and unphosphorylated
      CREB were bound to consensus/CRE in the proliferation stage. ATF-1 was also
      detected as a minor component bound to the consensus/CRE probe. The alteration of
      the binding of CREB to consensus/CRE over the course of osteoblast development
      supports the hypothesis that CREB may regulate the expression of genes defining
      the developmental sequence of MC3T3-E1 cells.

PMID- 9538222
TI  - Evidence for a novel ATP-dependent protease from the rat liver mitochondrial
      intermembrane space: purification and characterisation.
AB  - An ATP-dependent protease in the intermembrane space of rat liver mitochondria,
      MISP I (mitochondrial intermembrane space protease), was partially purified and
      characterised. The protease complex has a molecular mass of 200 kDa and appears
      to be an oligomeric enzyme complex. The proteolytic activity of the enzyme can be
      stimulated up to 3-fold by Mg2+ATP. The Km for ATP is 200 microM. Nucleoside
      triphosphates, but not ADP, AMP, or nonhydrolysable ATP analogues, can substitute
      for ATP. The protease exhibits multicatalytic properties with chymotrypsin-like,
      peptidyl-glutamyl-hydrolysing, and trypsin-like activities. Of the latter the
      trypsin-like activity is not enhanced by ATP. In addition to the hydrolysis of
      fluorogenic peptide substrates the protease is able to degrade radiolabeled model
      proteins. The ATP-dependent mitochondrial protease was characterised as a
      cysteine protease sensitive to hemine. The cross reactivity of an anti-human-S4
      antibody raised against an ATPase subunit of the PA700 complex with a component
      of MISP I indicated a structural relationship. Furthermore, ATP-agarose-binding
      assays revealed the connection of the peptide hydrolysing activity with an ATP
      binding domain. The data presented here and a comparison with known ATP-dependent
      mitochondrial proteases demonstrated that MISP I represents a novel ATP-dependent
      protease in the mitochondrial intermembrane space of rat liver.

PMID- 9538223
TI  - New imidazoles as probes of the active site topology and potent inhibitors of
      beta-glucosidase.
AB  - Series of 4-arylimidazoles, omega-N-acylhistamines and 4-(omega
      phenylalkyl)imidazoles were synthesized in order to probe the active site
      topology of sweet almond beta-glucosidase. These imidazole derivatives were shown
      to be very powerful competitive inhibitors. Among the 20 tested compounds, omega
      N-benzoylhistamine and 4-(3'-phenylpropyl)imidazole are the most potent
      inhibitors of the enzyme, with pH-independent Ki values of 0.06 and 0.07 microM,
      respectively. The inhibition of 4-(omega-phenylalkyl)imidazoles exhibited an
      interesting trend as to Ki values: 4-phenylimidazole (6.6 microM)>4
      benzylimidazole (1.4 microM)>4-(2'-phenylethyl)imidazole (0.82 microM)>4-(3'
      phenylpropyl)imidazole (0.07 microM)<4-(4'-phenylbutyl)imidazole (0.13 microM)<4
      (5'-phenylpentyl)imidazole (0.3 microM). This revealed that the imidazole and
      aryl binding sites (which result from favorable interactions within the
      corresponding glycone and aglycone binding subsites) are separated by the optimal
      distance equivalent to the length of a -CH2-CH2-CH2- group. Substitutions of the
      phenyl moieties of 4-phenylimidazole and 4-benzoylhistamine result in weaker
      inhibition. These classes of imidazoles are particularly powerful inhibitors of
      sweet almond beta-glucosidase.

PMID- 9538226
TI  - Expression of human alpha-lactalbumin in transgenic tobacco.
AB  - alphaLA-Lactalbumin (alphaLA), a major milk protein, is the regulatory subunit of
      lactose synthase. To assess the production of recombinant alphaLA in plants, the
      cDNAs for human alphaLA with or without its own signal sequence were introduced
      into tobacco plants under the control of the cauliflower mosaic virus 35S
      promoter. The gene integration and expression at the mRNA level were confirmed in
      several regenerated plants, while the expression at the protein level could be
      confirmed only in a transgenic tobacco transformed with the gene containing the
      signal sequence. The tobacco-expressed alphaLA migrated in SDS-PAGE with
      identical mobility to alphaLA prepared from human milk, indicating that the
      signal peptide of human alphaLA was correctly processed to yield a mature protein
      in tobacco plants. The expressed alphaLA (ca. 5 microg/g of fresh leaves) was
      found in the soluble fraction and eluted from a DEAE-Sepharose column in the same
      salt concentration range as the milk alphaLA. The partially purified tobacco
      alphaLA was fully active in the synthesis of lactose when combined with
      galactosyltransferase. Thus, the transgenic tobacco produces a fully active
      mature alphaLA in a soluble form.

PMID- 9538224
TI  - MS-430, a synthetic pyrimidine derivative, influences the intracellular signal
      transduction pathway leading to neuronal differentiation of PC12h cells.
AB  - Although NGF (nerve growth factor) induces neuronal differentiation of PC12
      cells, EGF (epidermal growth factor) acts as a mitogen for these cells. We have
      studied the effects of a synthetic pyrimidine derivative, MS-430, on the NGF and
      EGF actions on PC12h cells. We found that MS-430 accelerated NGF-induced neurite
      extension of PC12h cells and that, in the presence of MS-430, PC12h cells
      extended neurites in response to EGF. Next, we investigated the tyrosine
      phosphorylation of NGF receptor TrkA and the EGF receptor (EGFR) as well as
      mitogen-activated protein kinase (MAPK), which is a key protein in the
      intracellular signal transduction pathway. It was found that MS-430 prolonged the
      EGF-induced phosphorylation of EGFR and MAPK compared to that without MS-430. MS
      430 also prolonged the NGF-induced phosphorylation of MAPK, but the
      phosphorylation of TrkA induced by NGF was not affected by MS-430. These results
      suggest that MS-430 influences the intracellular signal transduction pathway
      which causes the neuronal differentiation of PC12h cells.

PMID- 9538225
TI  - Nitric oxide mediates interleukin-1-induced gene expression of matrix
      metalloproteinases and basic fibroblast growth factor in cultured rabbit
      articular chondrocytes.
AB  - We recently reported that nitric oxide (NO), which is produced by chondrocytes
      treated with interleukin-1beta (IL-1), releases basic fibroblast growth factor
      (bFGF) stored in the matrix of articular chondrocytes. To clarify the mechanism
      of the IL-1-induced bFGF release, we investigated the production and gene
      expression of bFGF, matrix metalloproteinases (MMPs), syndecan 3, and inducible
      NO synthase (iNOS) by IL-1-treated rabbit articular chondrocytes. IL-1 stimulated
      not only the release of bFGF but also the production of it. Gelatin and casein
      zymography revealed that IL-1 stimulated the production of not only MMP-9 but
      also MMP-3. The increase in the production of these MMPs preceded the IL-1
      stimulated bFGF release. An MMP inhibitor partially suppressed the release of
      bFGF, indicating that matrix degradation is at least partially involved in the IL
      1-stimulated bFGF release even if increased production of bFGF is related to the
      release. IL-1 sequentially stimulated mRNA expression of iNOS, membrane type 1
      MMP, MMP-9 and -3, and bFGF, in that order. NG-Monomethyl-L-arginine, an
      inhibitor of NO production, inhibited gene expression of MMP-9 and bFGF. These
      findings suggest that elevation of the NO level via iNOS mRNA expression
      stimulated by IL-1 mediates gene expression and production of MMPs and bFGF,
      resulting in the release of bFGF, and also reveal molecular mechanisms
      implicating the degradation of articular cartilage followed by angiogenesis in
      the synovium in arthritic joints.

PMID- 9538227
TI  - The conformational change induced by FAD in covalently flavinylated 6-hydroxy-D
      nicotine oxidase does not require (8alpha)FAD-(N3)histidyl bond formation.
AB  - The contribution of (8alpha)-(N3)histidyl bond formation to the conformation of
      covalently flavinylated proteins was investigated by trypsin treatment of wild
      type and mutant versions of a model enzyme, 6-hydroxy-D-nicotine oxidase (6-HDNO)
      of Arthrobacter nicotinovorans. In the absence of FAD, apo-6-HDNO exhibited a
      conformation exposing a protease accessible site. Holoenzyme formation through
      FAD-attachment to His71 induced a conformational change in the protein that
      shielded the trypsin recognition site. This conformational change, however, did
      not require FAD-histidyl bond formation since trypsin resistance was also
      exhibited by a 6-HDNO.Cys71 mutant protein which was unable to bind FAD
      covalently. Replacement of Arg67, an amino acid residue supposed to be essential
      in flavinylation, by Ala rendered the protein protease sensitive as did
      replacement of Pro73 by Ala. These amino acids apparently play an essential role
      in stabilizing the native protein conformation. The inability to reach the native
      conformation also prevented FAD attachment, indicating that a specific
      conformation of the protein is a prerequisite for FAD-histidyl bond formation.
      Deletion of Phe448 and Arg449 from the 458 amino acid residues-containing enzyme
      resulted in complete protease sensitivity, demonstrating that flavinylation takes
      place posttranslationally.

PMID- 9538228
TI  - RecA protein has extremely high cooperativity for substrate in its ATPase
      activity.
AB  - The single-stranded DNA-dependent ATPase activity of Escherichia coli RecA
      protein, especially its cooperativity for ATP, was investigated. To measure the
      ATPase activity in detail, the methods and reaction conditions for the ATPase
      assay were reexamined. Under conditions where RecA protein always showed a
      maximal rate of ATP hydrolysis, its poly(dT)-dependent ATPase activity was
      measured. At 25 degrees C, increasing the concentration of RecA protein from 0.3
      to 1.0 microM increased the turnover number (kcat) from 0.16 to 0.19 s-1 and the
      Hill coefficient (nH) for ATP from 9.3 to 11.6. At 0.5 microM RecA protein,
      increasing the temperature from 25 to 37 degrees C increased kcat from 0.18 to
      0.35 s-1 but decreased nH from 9.8 to 6.6. Interestingly, the ATPase activity of
      RecA protein measured in this study showed much higher cooperativity for ATP than
      those reported to date. Furthermore, the nH value of 11.6 for ATP obtained here
      was the highest of any ATPase reported so far. These results suggest that the
      binding of an ATP molecule to a RecA molecule within a nucleoprotein helical
      filament causes structural change of many other neighboring RecA molecules. This
      implies that ATP binding induces structural change of the whole nucleoprotein
      helical filament. Finally, we demonstrated that analysis of cooperativity is
      useful for revealing how a protein composed of many subunits functions as a
      whole.

PMID- 9538229
TI  - Characterization and developmental regulation of proteoglycan-type protein
      tyrosine phosphatase zeta/RPTPbeta isoforms.
AB  - Protein tyrosine phosphatase zeta (PTPzeta/RPTPbeta) is a receptor-like protein
      tyrosine phosphatase specifically expressed in the brain. Alternative splicing
      produces three isoforms of this molecule: PTPzeta-A, the full-length form of
      PTPzeta; PTPzeta-B, the short form of PTPzeta; and PTPzeta-S, an extracellular
      variant. Here, we identified all these isoforms, including PTPzeta-B, as
      chondroitin sulfate proteoglycans, and characterized their carbohydrate
      modification and expression profiles in the rat brain. The level of PTPzeta-A
      expression was maintained during the prenatal period and decreased rapidly after
      birth. PTPzeta-S was expressed in a similar manner, although the postnatal
      decrease was gradual. In contrast, relatively constant amounts of PTPzeta-B were
      observed from embryonic day 13 (E13) through adulthood. PTPzeta-A and -S were
      constantly expressed only as proteoglycans during development, but a substantial
      amount of PTPzeta-B was detected in a non-proteoglycan form at E13-15. Moreover,
      PTPzeta-B did not contain LeX, HNK-1 carbohydrate, or keratan sulfate, although
      PTPzeta-A and -S were generally modified with these carbohydrates. L cells
      transfected with PTPzeta-A and -B cDNAs expressed these proteins as enzymatically
      active chondroitin sulfate proteoglycans. The PTPzeta-A and -B in L cells showed
      essentially similar localizations in cell cortical structures on
      immunofluorescence microscopy, although immature or processed forms of PTPzeta-A
      were accumulated additively in intracellular patchy structures. These results
      show that the three isoforms of PTPzeta are differentially regulated during
      development, and that the extracellular deleted region in PTPzeta-B is important
      for determination of carbohydrate modification.

PMID- 9538230
TI  - A streptavidin-based neoglycoprotein carrying more than 140 GT1b
      oligosaccharides: quantitative estimation of the binding specificity of murine
      sialoadhesin expressed on CHO cells.
AB  - We prepared a streptavidin-based neoglycoprotein which carries more than 140 GT1b
      oligosaccharides. GT1b oligosaccharides were covalently coupled to streptavidin
      by reductive amination, yielding a monomer form of streptavidin carrying 13
      oligosaccharides. The monomer form of glycosylated streptavidin was polymerized
      with biotinylated-bovine serum albumin, which yielded a polymer carrying more
      than 140 oligosaccharides. Both the monomer and the polymer bound to Chinese
      hamster ovary cells expressing murine sialoadhesin. The relative binding
      potencies determined with the polymer, monomer, and free GT1b oligosaccharides
      were 3,500, 83, and 1, respectively, indicating that an increase in the number of
      oligosaccharide ligands is critical for high avidity. The high avidity of the
      polymer enabled us to develop a sensitive and quantitative binding assay, and the
      assay was applied to characterization of the binding specificity of sialoadhesin.
      The polymer binding was inhibited by various gangliosides, the order of the
      inhibitory potencies being GM3 (IC50 = 40 microM) > GD1a (100 microM) >
      sialylparagloboside (120 microM) > GT1b (310 microM) > GM2 (640 microM) > GM4
      (2,100 microM) > GD1b>LacCer = GM1 = paragloboside (no inhibition). These results
      indicate that the binding specificity is comparable to that reported, i.e. the
      determinant structure is NeuAcalpha2-3Galbeta1-linked to either 3GalNAc,
      3(4)GlcNAc, or 4Glc, and that the oligosaccharide structure on the polymer is
      properly presented to sialoadhesin on the cell surface. To determine the precise
      requirement of the NeuAc structure for binding, NeuAc of GM3 was converted into
      various derivatives, the inhibitory potencies of which were examined; i.e. GM3
      containing NeuAc, IC50 = 40 microM; C7- or C8-aldehyde, 500 microM; C7- or C8
      alcohol, 700 microM; C1-alcohol, 2,000 microM; C1-amide, 2,200 microM; and
      NeuGc,>3,000 microM. These results confirmed the requirement of the hydroxyl
      group at C9 and/or C8, the carboxyl group at C1, and the methyl group of the N
      acetyl residue of NeuAc in a quantitative manner. Thus, this streptavidin-based
      neoglycoprotein is a useful multivalent glycoprobe, which exhibits high affinity
      and specificity to murine sialoadhesin on the cell surface.

PMID- 9538231
TI  - Molecular cloning and expression of an amine sulfotransferase cDNA: a new gene
      family of cytosolic sulfotransferases in mammals.
AB  - A cDNA of amine sulfotransferase-RB1 (AST-RB1), which efficiently catalyzes 4
      phenyl-1,2,3,6-tetrahydropyridine (PTHP) sulfation, has been isolated by
      immunoscreening of a rabbit liver cDNA library. The cDNA consisted of 1,117 base
      pairs and encoded a protein of 301 amino acids with a molecular weight of 35,876.
      The deduced amino acid sequence matched at six positions those of peptide
      fragments obtained from purified AST-RB1 protein. The sequence had less than 38%
      identity at the amino acid level with cytosolic sulfotransferases in mammals,
      although high degrees of similarity were observed with regions conserved
      throughout mammalian sulfotransferases. These results indicate that AST-RB1,
      arbitrarily named sulfotransferase 3A1 (ST3A1), constitutes a new and third gene
      family of cytosolic sulfotransferases in mammals. ST3A1 expressed in Escherichia
      coli as a fused protein catalyzed sulfation of amines such as PTHP, aniline, 4
      chloroaniline, 2-naphthylamine, and desipramine, but barely O-sulfation of
      typical aryl and hydroxysteroid sulfotransferase substrates. These data
      unequivocally demonstrate the existence of a cytosolic sulfotransferase showing a
      high selectivity for amine substrates, and indicate that multiple forms of
      sulfotransferase mediate sulfation of xenobiotics in mammalian livers.

PMID- 9538232
TI  - Further characterization of equine brain gangliosides: the presence of GM3 having
      N-glycolyl neuraminic acid in the central nervous system.
AB  - Equine brain gangliosides were isolated and their structures were characterized,
      to examine whether equine brain has N-glycolyl neuraminic acid in gangliosides,
      since other mammals predominantly possess N-acetyl neuraminic acid in brain
      gangliosides, and equine erythrocytes and organs except the brain have
      gangliosides exclusively containing N-glycolyl neuraminic acid. The gangliosides
      purified from the brain were identified by proton NMR spectroscopy and mass
      spectrometry, as well as GLC, resulting in their identification as GM4, GM3, GM2,
      GM1, GD1a, GD1b, and GT1b. Of these gangliosides, GM3 possessed N-glycolyl
      neuraminic acid as a minor component (18% of the total GM3), whereas other
      gangliosides exclusively contained N-acetyl neuraminic acid. The N-glycolyl
      neuraminic acid residue of the GM3 was confirmed by TLC immunostaining. The
      possibility of contamination of the GM3 by erythrocytes was eliminated based on
      the finding that the lipid compositions were characteristic of brain
      gangliosides. The presence, even as a minor component, of the N-glycolyl
      neuraminic acid in equine brain gangliosides is exceptional among the sialic acid
      species in mammalian central nervous system.

PMID- 9538233
TI  - Antibody against single-stranded DNA useful for detecting apoptotic cells
      recognizes hexadeoxynucleotides with various base sequences.
AB  - Our previous study demonstrated that an antibody against single-stranded DNA
      could detect apoptotic cells [Naruse et al. (1994) Histochemistry 101, 73-78]. In
      this paper we describe the development of an improved method for the production
      of the antibody and investigations into the antigenic determinants of the
      antibody so that it could be of practical use for detecting apoptotic cells.
      Rabbits, hyperimmunized with complexes of alkaline-denatured calf thymus DNA and
      methylated bovine serum albumin, produced an IgG antibody to single-stranded DNA.
      Analysis by sandwich ELISA using various naturally occurring nucleic acids
      revealed that the antibody was specific to single-stranded DNA. Furthermore,
      using synthetic polymers in the assay, it was found that the antibody could
      recognize single-stranded DNA with various base sequences. Gel electrophoresis
      retardation assays, with synthetic oligodeoxynucleotides with differing lengths
      of single-stranded DNA, indicated that a hexadeoxynucleotide constituted the
      minimum size of the antigenic determinants, and suggested that the antibody
      probably consists of several antibodies which recognize hexadeoxynucleotides with
      various base sequences. Western blot analysis demonstrated that the antibody can
      recognize both a DNA ladder and oligonucleosomes prepared from rat liver nuclei
      with endogenous endonuclease. The present findings demonstrate that this antibody
      is a useful tool for detecting apoptotic cells.

PMID- 9538234
TI  - Cloning and characterization of a cDNA encoding a novel heterogeneous nuclear
      ribonucleoprotein-like protein and its expression in myeloid leukemia cells.
AB  - We isolated a cDNA encoding a novel heterogeneous nuclear ribonucleoprotein
      (hnRNP)-like protein on DNA affinity screening of a K562 cDNA expression library
      with an oligodeoxynucleotide (JKT41) derived from intron 9 of the human
      myeloperoxidase gene. The cDNA has a 1,305 bp sequence that encodes a polypeptide
      of 301 amino acid residues. The protein, named JKTBP, contains two repeats of a
      putative RNA binding domain (RBD), each composed of canonical RNP-2 and RNP-1
      motifs, and a glycine- and tyrosine-rich carboxyl terminus. The sequences of
      these two repeats are highly homologous with those of the 2 x RBD-Gly rich group
      of hnRNPs. Northern blotting showed that two mRNAs of approximately 1.4 and 2.8
      kb were present in most cultured cells examined. The recombinant protein
      expressed in Escherichia coli interacted with the double-stranded form of JKT41
      as well as with its single-stranded form. This interaction was competitively
      inhibited by the same unlabeled JKT41 and to nearly the same extent by unrelated
      oligonucleotides. Moreover, the recombinant protein interacted with poly(G) and
      poly(A), but not with poly(U) or poly(C). Transient expression of the protein in
      SKM-1 cells repressed the expression of chloramphenicol acetyltransferase
      reporter genes located downstream of the intron 9 element of JKT41 or intron 7
      element of FERE27. The implications of the protein in the biogenesis of mRNA are
      discussed.

PMID- 9538235
TI  - Chemo-enzymatic synthesis of galactosylmaltooligosaccharidonolactone as a
      substrate analogue inhibitor for mammalian alpha-amylase.
AB  - We performed chemo-enzymatic transformation of maltooligosaccharides into both
      end-modified oligosaccharidonolactones of potential use as substrate analogue
      inhibitors for mammalian alpha-amylases. Enzymatic modification of the non
      reducing end glucosyl residue of the maltooligosaccharide was first performed by
      transglycosylation with beta-D-galactosidase from Bacillus circulans. When
      maltotriose and maltotetraose were the acceptors, the enzyme regioselectively
      synthesized 4(3)-O-beta-D-galactosyl maltotriose (LG3) and 4(4)-O-beta-D
      galactosyl maltotetraose (LG4) from lactose as a donor. LG4 was further
      selectively hydrolyzed with a specific alpha-amylase to afford 4(2)-O-beta-D
      galactosyl maltose (LG2). The anomer hydroxyl groups of LG2 and LG3 were
      chemically oxidized to give the corresponding lactones, 4(2)-O-beta-D-galactosyl
      maltobionolactone (LG2O) and 4(3)-O-beta-D-galactosyl maltotrionolactone (LG3O),
      respectively. LG2O and LG3O, which are competitive inhibitors for mammalian alpha
      amylases, exhibited Ki values of the order of 2.8-18.0 microM, with p-nitrophenyl
      alpha-maltopentaoside (G5P) as the substrate. On 1H-NMR analysis, these
      oligosaccharidonolactones were shown to be transformed into the corresponding
      aldonic acid forms with time in an aqueous solution. In this case, the lactone
      form was essential for the occurrence of the alpha-amylase inhibitor.

PMID- 9538236
TI  - Oxidative refolding of bovine pancreatic RNases A and B promoted by Asn-glycans.
AB  - It was previously revealed [Yamaguchi, H. and Uchida, M. (1996) J. Biochem. 120,
      474-477] that both intra- and extramolecular high-mannose type Asn-glycans
      promote the renaturation of reductively denatured bovine pancreatic RNases A and
      B under oxidation conditions. To characterize the conformational changes of the
      polypeptides during the renaturation promoted by the intramolecular Asn-glycans,
      RNase B was compared with its nonglycosylated form, RNase A, as to the features
      of the regeneration from their reductively denatured species under Cu2+-catalyzed
      oxidation conditions. The refolding intermediates of RNase B, as compared with
      those of RNase A, seemed to contain much less impaired disulfide linkages. In
      agreement with this finding, the proper refolding of RNase B was much faster than
      that of RNase A, as revealed by the intrinsic fluorescence and 1-anilino-8
      naphthalenesulfonate binding of the refolding intermediates. Such a promoting
      effect was also observed for extramolecular Asn-glycans of the complex as well as
      of the high-mannose type. In contrast, common mono-, oligo-, and polysaccharides,
      but not yeast mannan, exhibited much lower stimulatory effects on the oxidative
      refolding of RNase A.

PMID- 9538237
TI  - Purification and characterization of a [3Fe-4S][4Fe-4S] type ferredoxin from
      hyperthermophilic archaeon, Pyrobaculum islandicum.
AB  - A ferredoxin was purified from the hyperthermophilic archaeon, Pyrobaculum
      islandicum. EPR spectra and metal content analyses suggested that the ferredoxin
      molecule contained one [3Fe-4S] and one [4Fe-4S] cluster. The ferredoxin was
      rapidly reduced by 2-oxoglutarate: ferredoxin oxidoreductase purified from P.
      islandicum, indicating that it functions physiologically as an electron sink for
      the redox enzymes participating in glycolytic metabolism. Furthermore, the amino
      acid sequence of the P. islandicum ferredoxin was compared with those of several
      other bacterial ferredoxins.

PMID- 9538238
TI  - Trans-activation of the Tetrahymena ribozyme by its P2-2.1 domains.
AB  - The Tetrahymena group I self-splicing intron contains peripheral domains P2-2.1.
      Mutant introns lacking these domains are hardly active. We found that if an
      independently prepared P2-2.1 RNA is added in trans, it efficiently enhances the
      catalytic activity of an intron lacking the domains. P2-2.1 RNA together with the
      previously identified activator, P5abc RNA, of the Tetrahymena intron can
      activate the intron lacking both of them. The trans-activation depends on the
      long-range interaction between P2.1 and P9.1 domains.

PMID- 9538239
TI  - Metabolism of 4-hydroxynonenal, a cytotoxic lipid peroxidation product, in
      thymocytes as an effective secondary antioxidative defense mechanism.
AB  - The metabolism of the aldehydic lipid peroxidation product, 4-hydroxynonenal
      (HNE),was studied in suspensions of mouse thymocytes. Thymocytes are
      characterized by low lipid peroxidation in comparison with other cell types
      notwithstanding their high content of arachidonic acid. In our study a very high
      capacity of HNE metabolism in thymocytes was observed: 27.7 nmol/mg w.w./min.
      That is about the same HNE degradation rate as determined in liver cells or small
      intestinal enterocytes, which are the cells with the by far highest capacity for
      the degradation of HNE and other aldehydic lipid peroxidation products in
      comparison with other cell types. The primary and secondary HNE metabolites in
      thymocytes were identified and quantified after the addition of 100 microM HNE to
      thymocyte suspensions: the glutathione-HNE conjugate, the hydroxynonenoic acid,
      the 1,4-dihydroxynonene, water, and the glutathione-dihydroxynonene conjugate.
      Furthermore, the HNE binding to proteins was measured. The very rapid HNE
      degradation in thymocytes besides the high amounts of lipophilic chain-breaking
      antioxidants is postulated to be an important secondary antioxidative mechanism
      and the main factor for the low accumulation of lipid peroxidation products in
      these cells.1668

PMID- 9538240
TI  - cDNA cloning of mouse prolyl endopeptidase and its involvement in DNA synthesis
      by Swiss 3T3 cells.
AB  - A cDNA for mouse prolyl endopeptidase (PEP) was cloned and its nucleotide
      sequence determined. The overall amino acid sequence identity between mouse and
      other mammalian PEPs was about 96%. A specific inhibitor of PEP, N
      benzyloxycarbonyl-thioprolyl-thioprolinal- dimethylacetal (ZTTA), inhibited DNA
      synthesis by Swiss 3T3 cells. Mouse PEP was shown to be localized partly in
      restricted nuclear regions. These results suggest that PEP participates in
      mammalian DNA synthesis.

PMID- 9538241
TI  - Caldecrin is a novel-type serine protease expressed in pancreas, but its
      homologue, elastase IV, is an artifact during cloning derived from caldecrin
      gene.
AB  - As reported previously, caldecrin, a serum calcium-decreasing factor, from
      pancreas was found to be a serine protease, but the proteolytic activity was not
      necessary for its serum calcium decreasing activity. The caldecrin cDNA encoded a
      protease zymogen of the chymotrypsin/elastase superfamily consisting of a signal
      peptide, an activation peptide and a mature enzyme. On a homology search, we
      found that the sequence of rat caldecrin is almost identical to that of rat
      elastase IV (nucleotides: 99.3%175B amino acids: 90.3%) with the exception of the
      central region. However, it is not known whether or not elastase IV is
      transcribed and translated in vivo, and has proteolytic activity. In the present
      study, we constructed a rat elastase IV cDNA by means of combinatorial PCR, and
      compared the recombinant elastase IV with the recombinant caldecrin synthesized
      in a baculovirus expression system. The recombinant caldecrin protein was
      expressed in the cells and secreted mainly into the medium. In contrast, in the
      case of elastase IV, no recombinant protein was immunologically or enzymatically
      detected in the medium, while an immunoreactive protein with much lower protease
      activity was found in the cells in an amount comparable to that of the caldecrin
      protein. Using the RT-PCR method to discriminate caldecrin mRNA from elastase IV
      mRNA, we detected caldecrin mRNA expression in rat pancreas, but no elastase IV
      mRNA expression in any tissues examined. PCR analysis of rat genomic DNA revealed
      the presence of caldecrin and the absence of elastase IV sequences. These results
      indicate that caldecrin is expressed in the pancreas, but that elastase IV is an
      artifact produced during cloning. Furthermore, we investigated the protein
      chemical and enzymological properties of the rat and human caldecrins using their
      recombinant proteins. Both recombinant proteins were secreted into the medium as
      proforms and showed protease activity after trypsin treatment. Some differences
      were found in the activation process and stability between human and rat
      caldecrins; human caldecrin was more easily activated by trypsin, but was much
      more labile than rat caldecrin. Although both caldecrins were found to be
      chymotrypsin-type proteases, on the basis of their substrate and inhibitor
      specificities, they were not inhibited by TPCK, suggesting that caldecrin is a
      novel type of serine protease.

PMID- 9538242
TI  - His-Asp phosphotransfer signal transduction.
AB  - In general, protein phosphorylation is one of the most widely used mechanisms for
      regulating biological processes, including intracellular signal transduction. In
      eukaryotes, the cascades of protein phosphorylation and dephosphorylation events
      involving a number of protein tyrosine or serine/threonine kinases have been well
      studied. In contrast, recent intensive studies revealed that bacteria have
      devised a quite different phosphotransfer signaling mechanism for eliciting a
      variety of adaptive responses to their environment. Such a bacterial signal
      transduction mechanism was originally referred to as a "two-component regulatory
      system." The mode of molecular communication between a "sensor kinase" and its
      cognate phospho-accepting "response regulator" is principally based on histidine
      to-aspartate (His-Asp) phosphotransfer. In Escherichia coli, for example, at
      least 30 different sensor-regulator pairs operate in a wide variety of adaptive
      responses. This particular signal transduction mechanism was once thought to be
      restricted to prokaryotes. However, many instances have recently been uncovered
      in diverse eukaryotic species. Furthermore, recent studies suggested that the
      molecular mechanism underlying the bacterial signal transduction is not simple
      as, and, in fact, is more sophisticated than thought previously. The new concept
      should be referred to as the "multi-step His-Asp phosphotransfer signaling
      mechanism."

PMID- 9538243
TI  - Guanidine hydrochloride-induced changes of the E2 inner core of the Bacillus
      stearothermophilus pyruvate dehydrogenase complex.
AB  - The limited proteolysis of the Bacillus stearothermophilus pyruvate dehydrogenase
      complex by V8 protease yields its core structure solely composed of lipoate
      acetyltransferase (E2) fragments. The changes in the core with guanidine
      hydrochloride (GdnHCl) were biphasic: below 0.8 M (first) and above 1.0 M
      (second) GdnHCl. The changes in the first phase were slight but significant:
      decreases in ellipticity and light scattering, and an increase in E2 activity.
      Insignificant changes in the molecular shape and size of the core were detected
      on fluorescence spectroscopy, ultracentrifugation, gel filtration, and electron
      microscopy. On the other hand, the changes in the second phase were drastic; the
      core was disassembled and denatured.

PMID- 9538244
TI  - Crystallization and preliminary X-ray diffraction studies of a rice cysteine
      proteinase inhibitor, Oryzacystatin-I.
AB  - Oryzacystatin-I from rice seeds was overexpressed in Escherichia coli, purified,
      and crystallized by the sitting-drop vapor diffusion method. Crystals obtained
      with 2-methyl-2,4-pentanediol as a precipitant exhibited space group I4122, with
      unit cell parameters of a = b = 100.0 A, c = 54.2 A, and diffracted up to 2.8 A
      resolution at 100 K. The crystals have one molecule per asymmetric unit.

PMID- 9538245
TI  - Actin-depolymerizing effect of dimeric macrolides, bistheonellide A and
      swinholide A.
AB  - We compared the effects of dimeric marine toxins, bistheonellide A, and
      swinholide A, on actin polymerization. Bistheonellide A and swinholide A possess
      two identical side chains with similar structures to those of other marine
      toxins, mycalolide B, and aplyronine A. By monitoring changes in fluorescent
      intensity of pyrenyl-actin, bistheonellide A was found to inhibit polymerization
      of G-actin and to depolymerize F-actin in a concentration-dependent manner. The
      relationship between the concentration of bistheonellide A and its inhibitory
      activity on actin polymerization suggested that one molecule of bistheonellide A
      binds two molecules of G-actin. We demonstrated by SDS-PAGE that the complex of G
      actin with bistheonellide A, swinholide A, or mycalolide B could not interact
      with myosin. No evidence was found that bistheonellide A severs F-actin at the
      concentrations examined (molar ratio to actin; 0. 025-2.5), while swinholide A
      showed severing activity, although it was weaker than that of mycalolide B. We
      also demonstrated that the depolymerizing effect of bistheonellide A or
      mycalolide B is irreversible. Bistheonellide A increased, while swinholide A
      decreased, the rate of nucleotide exchange in G-actin, suggesting that binding of
      these toxins induces different conformational changes in the actin molecule.
      These results suggest that bistheonellide A intervenes between two actin
      molecules, forms a tertiary complex with each of its side chains bound to G
      actin, and inhibits polymerization by sequestering G-actin from incorporation
      into F-actin. A difference in structure at the end of the side chain between
      dimeric macrolides and mycalolide B may account for the weak severing activity of
      the former.

PMID- 9538246
TI  - Cellular distribution of a GPI-anchored complement regulatory protein CD59:
      homodimerization on the surface of HeLa and CD59-transfected CHO cells.
AB  - Human glycosyl phosphatidylinositol-anchored protein CD59 was solubilized in
      detergent-insoluble complexes (DICs) and in post-nuclear pellets by a two-step
      solubilization procedure using Triton X-100 and octylglucoside. CD59 molecules
      are recovered in both fractions, the amount being greater in the latter fraction
      in all cell types tested. Specific labeling of surface CD59 molecules revealed
      that the CD59 detected in DICs originated from intracellular compartments,
      whereas that in post-nuclear pellets was in part derived from the cell surface.
      Cross-linking of surface proteins with chemical cross-linker followed by Western
      blotting with anti-CD59 antibody revealed cross-linked products with molecular
      masses of 28-36 kDa on HeLa and human CD59 cDNA-transfected CHO cells; the CD59
      associating molecules were estimated to be 13-18 kDa in size. The cross-linked
      products were extracted in the post nuclear pellets, and CD59 existed mainly as a
      cross-linked form on the cell surface. Two-dimensional electrophoresis of the
      cross-linked products revealed no trace of molecules other than CD59. The cross
      linked products showed the same N-terminal sequences as CD59 and a strikingly
      similar amino acid composition to that of CD59. Thus, most likely, the cross
      linked products are CD59 dimers. The finding that CD59 localized on outer
      membranes is all in the form of dimers suggests the importance of dimerization
      for CD59 functioning.

PMID- 9538247
TI  - Analysis of matrix protein components of the dermis-like structure formed in a
      long-term culture of human fibroblasts: type VI collagen is a major component.
AB  - Formation of a dermis-like structure by a long-term culture of fibroblasts in the
      presence of ascorbic acid is a potential model for tissue organization or wound
      healing, and has its practical use as a skin graft. In the present study,
      solubilization of the dermis-like structure without pepsin treatment was
      attempted for analysis of pepsin-labile matrix components that might be involved
      in the formation of the dermis-like structure, as well as quantification of
      mutated type I collagen that could be susceptible to pepsin. The whole dermis
      like structure was dissolved in a Tris buffer containing SDS and urea at 80
      degreesC. Analysis of the extract by SDS-PAGE revealed several protein bands that
      were not found in the pepsin-treated extract. Among them, the polypeptide band
      migrating at 140k under reducing condition showed a similar intensity of protein
      staining to the alpha2(I) chain band. The N-terminal amino acid sequences of
      cyanogen bromide peptides derived from the 140k polypeptide band as well as the
      amino acid composition of the band suggested that the band essentially consisted
      of alpha1(VI) and alpha2(VI) chains. The results demonstrated that the type VI
      collagen was a major component, being a comparable in amount to type I collagen,
      in the dermis-like structure.

PMID- 9538248
TI  - Hypocholesterolemic effects of the LDL receptor gene transcriptional upregulator
      CP-230821.
AB  - CP-230821 is a novel, potent LDL receptor gene transcriptional upregulator which
      decreases total plasma cholesterol level. Interestingly, this plasma LDL decrease
      does not alter hepatic lipid contents. A series of experiments was undertaken to
      study the molecular biology of this phenomenon. Twelve hours after CP-230821
      treatment, the transcriptional activity and mRNA level of the LDL receptor gene
      in HepG2 cells were increased by 264% and 426%, respectively. Although treatment
      with the HMG-CoA reductase inhibitor compactin also increased LDL receptor gene
      transcription and mRNA, CP-230821 did not increase the level of HMG-CoA reductase
      gene transcription or mRNA. These results indicate that LDL receptor gene
      activity may play an important role in the decrease of plasma LDL level. These
      results further suggest that the LDL receptor gene and the HMG-CoA reductase gene
      are not strictly coordinately controlled.

PMID- 9538249
TI  - D-erythrulose reductase can also reduce diacetyl: further purification and
      characterization of D-erythrulose reductase from chicken liver.
AB  - We have discovered new characteristics of D-erythrulose reductase, namely, that
      it can catalyze reduction of not only D-erythrulose but also such diketones as
      diacetyl. These substrates have a common structure with two neighboring carbonyls
      possibly in s-cis plane structure, showing that the enzyme may rigorously
      distinguish between substrates and other compounds. D-Erythrulose reductase was
      predominantly located in the kidney and the liver of the chicken. The obtained
      results suggest that D-erythrulose reductase plays an important role in
      metabolizing alpha-dicarbonyls in animal organs, because these diketones widely
      occur in natural foods.

PMID- 9538250
TI  - A new Tetrahymena actin-binding protein is localized in the division furrow.
AB  - Using an F-actin affinity column, a 60 kDa fragment of a 71 kDa F-actin-binding
      protein was partially purified from Tetrahymena pyriformis. After digestion of
      the 60 kDa fragment with cyanogen bromide, the N-terminal 21-amino acid sequence
      of one of the resulting peptides was found to show sequence similarity to a
      region near the actin-binding site (amino acid residues 260-281) of yeast
      fimbrin. An antibody prepared against a synthesized 21-mer oligopeptide reacted
      with the 71 kDa proteins in T. pyriformis and T. thermophila cell extracts,
      suggesting that the 60 kDa fragment was produced from the 71 kDa protein through
      partial digestion occurring during isolation. The 60 kDa fragment bound to
      Tetrahymena F-actin as well as to rabbit skeletal muscle F-actin, and induced the
      bundling of Tetrahymena F-actin. Indirect immunofluorescence revealed
      colocalization of the 71 kDa protein and actin in the oral apparatus and the deep
      fiber bundles in T. pyriformis. On the other hand, in T. thermophila, the 71 kDa
      protein was localized in the oral apparatus and the contractile vacuole pores
      during the interphase. During cytokinesis, the 71 kDa protein was localized in
      the division furrow. Therefore, the 71 kDa protein seems to associate with the
      actin cytoskeleton, and to regulate the actin filament organization during
      phagocytosis and cytokinesis in Tetrahymena.

PMID- 9538251
TI  - Direct observation of a central bare zone in a native thick filament isolated
      from the anterior byssus retractor muscle of Mytilus edulis using fluorescent ATP
      analogue.
AB  - To investigate the existence of a central bare zone in native thick filaments
      isolated from the anterior byssus retractor muscle (ABRM) of blue mussels
      (Mytilus edulis), the filaments were observed by fluorescence and dark-field
      microscopy after being incubated in the presence of Ca2+ with the fluorescent ATP
      analogue, Cy3-EDA-ATP. Filaments appeared under dark-field illumination as thin
      rods with tapered ends of length 5-30 microm. Fluorescence microscopy revealed
      that Cy3-EDA-ATP was bound to these filaments, except near their center. Although
      the boundary between this central non-fluorescent zone and fluorescent regions
      was not clearly defined, there was a trend for the width of the central non
      fluorescent zone to increase with thick filament length (correlation coefficient
      = 0.45; n = 142). When Cy3-EDA-nucleotides bound to thick filaments were
      displaced by excess ATP, fluorescent images disappeared with a rate constant of
      0. 024 s-1, close to the turnover rate of Cy3-EDA-ATP by myosin on the native
      thick filaments. These results indicate that each native thick filament isolated
      from the ABRM has a central bare zone, but its boundary was not sharply resolved.

PMID- 9538252
TI  - Crystal structure of human secretory phospholipase A2-IIA complex with the potent
      indolizine inhibitor 120-1032.
AB  - Phospholipase A2 is a key enzyme in a number of physiologically important
      cellular processes including inflammation and transmembrane signaling. Human
      secretory phospholipase A2-IIA is present at high concentrations in synovial
      fluid of patients with rheumatoid arthritis and in the plasma of patients with
      septic shock. Inhibitors of this enzyme have been suggested to be therapeutically
      useful non-steroidal anti-inflammatory drugs. The crystal structure of human
      secretory phospholipase A2-IIA bound to a novel potent indolizine inhibitor (120
      1032) has been determined. The complex crystallizes in the space group P3121,
      with cell dimensions of a = b = 75.8 A and c = 51.3 A. The model was refined to
      an R-factor of 0. 183 for the intensity data collected to a resolution of 2.2 A.
      It was revealed that the inhibitor is located near the active site and bound to
      the calcium ion. Although the binding mode of the 120-1032 inhibitor to human
      secretory phospholipase A2-IIA is similar to that previously determined for an
      indole inhibitor LY311299, the specific interactions between the enzyme and the
      inhibitor in the present complex include the oxycarboxylate group which was
      introduced in this inhibitor. The oxycarboxylate group in 120-1032 is coordinated
      to the calcium ion and included in the water-mediated hydrogen bonding to the
      catalytic Asp49. In addition, the ethyl group in 120-1032 gains hydrophobic
      contacts with the cavity wall of the hydrophobic channel of the enzyme.

PMID- 9538253
TI  - Depolarization-induced tyrosine phosphorylation of p130(cas).
AB  - KCl-treatment of PC12 cells induces depolarization of the plasma membrane and
      Ca2+ influx into the cells. We have previously shown that KCl induced tyrosine
      phosphorylation of cellular proteins of 120, 110, 68, 44, and 42 k, and that the
      68 k protein was paxillin. In the present study, we found that the 120 k protein
      was a Crk-associated Src substrate, p130(cas). KCl-induced tyrosine
      phosphorylation of p130(cas) was not observed in EGTA-containing medium,
      suggesting that it was due to Ca2+ influx into the cells. Time course experiments
      showed that tyrosine phosphorylation of p130(cas) peaked at 5 min after
      stimulation and returned to the basal level at 60 min, while mobility shift of
      p130(cas) was observed within 2 min and lasted over 60 min, indicating that
      serine or threonine residues, in addition to tyrosine, were phosphorylated on KCl
      stimulation. In vitro kinase assay of immunoprecipitates with anti-p130(cas)
      antibody suggested that some protein-tyrosine kinases were associated with
      p130(cas). Using the substrate region of p130(cas) as the substrate, we found
      that Fyn and Src were activated on stimulation with KCl. These results indicate
      that tyrosine phosphorylation of p130(cas) may be involved in Ca2+-dependent
      events in neuronal and neuroendocrine cells.

PMID- 9538254
TI  - Disintegration of lysosomes mediated by GTPgammaS-treated cytosol: possible
      involvement of phospholipases.
AB  - We showed previously that cytosol treated with guanosine 5'-O-(3
      thiotriphosphate) (GTP-gammaS) disintegrated lysosomes in vitro [Sai, Y. et al.
      (1994) Biochem. Biophys. Res. Commun. 198, 869-877] in time-, temperature-, and
      dose-dependent manners. This also requires ATP, however, the latter can be
      substituted with deoxy-ATP, ADP, or ATPgammaS, suggesting no requirement of ATP
      hydrolysis. The lysis was inhibited by several chemical modifiers, including N
      ethylmaleimide, 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole, and 4,4'
      diisothiocyanatostilbene-2,2'-disulfonic acid, and by various phospholipase
      inhibitors (trifluoperazine, p-bromophenacyl bromide, nordihydroguaiaretic acid,
      W-7, primaquine, compound 48/80, neomycin, and gentamicin), but not by ONO-RS
      082, an inhibitor of phospholipase A2. The reaction was also inhibited by
      phospholipids (phosphatidylinositol, phosphatidylserine, phosphatidic acid, and
      phosphatidylcholine) and diacylglycerol. Among the phospholipase A2 hydrolysis
      products of phospholipids, unsaturated fatty acids (oleate, linoleate, and
      arachidonate) and lysophospholipid (lysophosphatidylcholine) by themselves broke
      lysosomes down directly, whereas saturated fatty acids (palmitate and stearate)
      had little effect. We found that GTPgammaS-stimulated cytosolic phospholipase A2
      activity was highly sensitive to ONO-RS-082. These results suggest the
      participation of phospholipase(s), though not cytosolic phospholipase A2, in the
      GTPgammaS-dependent lysis of lysosomes.

PMID- 9538255
TI  - ARF-induced lysosomal lysis in vitro.
AB  - Cytosol treated with guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS)
      disintegrated lysosomes in a dose-dependent manner, as detected as the release of
      preloaded fluorescein isothiocyanate-dextran. The effect of GTPgammaS was
      suppressed by GTP or GDP, indicating a role of a GTP binding protein (G-protein)
      in the lysis [Sai, Y. et al. (1994) Biochem. Biophys. Res. Commun. 198, 869-877].
      Gel filtration of cytosol and GTP-ligand blotting showed that a small GTP-binding
      protein participated in the lysosomal lysis. We partially purified the G-protein
      from rat liver cytosol and identified it as ARF1. GTPgammaS-stimulated lysis was
      reconstituted with ARF1 purified from bovine brain cytosol or recombinant ARF1.
      ARF bound to lysosomal membranes depending upon GTPgammaS in a dose-dependent
      manner. These results suggest that the transfer of ARF from the cytosol to the
      lysosomal membrane is necessary for GTPgammaS-stimulated lysis of lysosomes.

PMID- 9538256
TI  - Hydrogen evolution by direct electron transfer from photosystem I to
      hydrogenases.
AB  - H2 evolution by direct electron transfer from the dithionite-reduced photosystem
      I (PSI) complex to both hydrogenase I and hydrogenase II from Clostridium
      pasteurianum was observed. Evidence indicates that the electron carriers on PSI
      that transfer electrons to hydrogenase in this system are the FA/FB iron-sulfur
      clusters on the PsaC polypeptide, the terminal bound electron acceptors in PSI.
      Light-dependent H2 evolution was also observed, using high potential electron
      donors to PSI, from a combination of hydrogenase I and either solubilized
      purified PSI or thylakoids. Mediators capable of transferring electrons from the
      PSI complex to hydrogenase were not necessary for H2 evolution, indicating again
      that the mechanism of H2 evolution is direct electron transfer from PSI to
      hydrogenase, and that this can occur with light-reduced as well as chemically
      reduced PSI, and with PSI in thylakoids as well as the solubilized complex. Light
      dependent H2 evolution was also observed from a mixture of thylakoids and the
      oxygen-resistant hydrogenase of Rhodococcus sp. MR11. These results suggest that
      direct electron transfer from PSI to hydrogenase could be engineered to occur in
      vivo in a photosynthetic organism to create an organism that would efficiently
      produce H2 from H2O.

PMID- 9538257
TI  - Purification and characterization of myonase from X-chromosome linked muscular
      dystrophic mouse skeletal muscle.
AB  - A chymotrypsin-like proteinase, designated myonase, was successfully purified to
      homogeneity from X-chromosome linked muscular dystrophic mouse skeletal muscle by
      affinity chromatography on agarose conjugated with lima bean trypsin inhibitor as
      ligand. The molecular mass of the purified myonase was determined to be 26 kDa by
      SDS-PAGE and to be 25,187 Da by mass spectrometry. The native enzyme is a single
      chain molecule and a monomeric protein without sugar side-chains. The nucleotide
      sequence of myonase mRNA is similar to mouse mast cell proteinase 4 (MMCP-4)
      cDNA. This is the first report of a native enzyme whose amino acid sequence
      closely corresponds to MMCP-4 cDNA. Myonase has chymotrypsin-like activities and
      hydrolyzes the amide bonds of synthetic substrates having Tyr and Phe residues at
      the P1 position. Myonase is most active at pH 9 and at high concentration of
      salts. Myonase preferentially hydrolyzes the Tyr4-Ile5 bond of angiotensin I and
      the Phe20-Ala21 bond of amyloid beta-protein, and it is less active towards the
      Phe8-His9 bond of angiotensin I and the Phe4-Ala5 and Tyr10-Glu11 bonds of
      amyloid beta-protein. Myonase is completely inhibited by such serine proteinase
      inhibitors as chymostatin, diisopropylfluorophosphate and phenylmethylsulfonyl
      fluoride, but not by p-tosyl-L-phenylalanine chloromethyl ketone, p-tosyl-L
      lysine chloromethyl ketone, pepstatin, E-64, EDTA, and o-phenanthroline. It is
      also inhibited by lima bean trypsin inhibitor, soy bean trypsin inhibitor, and
      human plasma alpha1-antichymotrysin. These properties match those of chymase, but
      unlike chymase, myonase does not interact with heparin in the regulation of its
      activity. Myonase was immunohistochemically localized in myocytes, but not in
      mast cells.

PMID- 9538258
TI  - Functional involvement of mSos in interleukin-3 and thrombin stimulation of the
      Ras, mitogen-activated protein kinase pathway in BaF3 murine hematopoietic cells.
AB  - Stimulation of the interleukin (IL)-3 receptor provokes rapid activation of the
      Ras pathway in various hematopoietic cell lines. Also, a wide range of G-protein
      coupled receptors induce Ras activation following ligand stimulation. In this
      report, we investigate the mechanism underlying Ras activation upon stimulation
      of these two types of receptors in hematopoietic cells. Thrombin, a G-protein
      coupled receptor ligand, was found to stimulate extracellular signal-regulated
      kinase (ERK)/mitogen-activated protein kinase (MAPK) in IL-3-dependent BaF3
      cells, suggesting a significant function of thrombin receptor-mediated signaling.
      We show that the Ras-guanine nucleotide exchange factor mSos is indispensable for
      activation of the Ras pathway in IL-3- or thrombin-stimulated BaF3 cells. The
      activation of Ras in response to IL-3 as defined by accumulation of the GTP-bound
      form was impaired by conditional overexpression of a dominant-negative mutant of
      mSos (DeltamSos1). Furthermore, following induction of DeltamSos1, IL-3
      enhancement of the kinase activities of c-Raf-1, ERK2, and JNK1 downstream of Ras
      was almost completely blocked. Similarly, thrombin-induced Ras-dependent ERK2
      activation was diminished by DeltamSos1. However, the tyrosine phosphorylation
      pattern of cellular substrates upon thrombin stimulation was entirely different
      from the pattern of IL-3-induced tyrosine phosphorylation. Collectively, these
      results provide evidence that mSos plays a crucial role in both IL-3 and thrombin
      activation of the Ras pathway in hematopoietic cells, although molecules
      (including tyrosine kinases) mediating the signal to mSos are likely to be
      different between the two types of receptors.

PMID- 9538259
TI  - Crystal structure of eucaryotic E3, lipoamide dehydrogenase from yeast.
AB  - The crystal structure of eucaryotic lipoamide dehydrogenase from yeast has been
      determined by an X-ray analysis at 2.7 (partially at 2.4) A resolution. The
      enzyme has two identical subunits related by a pseudo twofold symmetry. The
      tertiary structure is similar to those of other procaryotic enzymes. The active
      site, consisting of FAD, Cys44, and Cys49 from one subunit and His457' from the
      other subunit, is highly conserved. This enzyme is directly bound to the core
      protein E2 of the 2-oxoglutarate dehydrogenase complex, whereas it is bound to
      the pyruvate dehydrogenase complex through a protein X. The calculated
      electrostatic potential suggests two characteristic regions for binding with
      these two proteins.

PMID- 9538260
TI  - Purification, primary structure, and antimicrobial activities of bovine
      apolipoprotein A-II.
AB  - We purified an antimicrobial protein of 76 residues, denoted bovine antimicrobial
      protein-1 (BAMP-1), from fetal calf serum using hydrophobic chromatography, gel
      filtration, and reverse-phase high-performance liquid chromatography. The amino
      acid sequence of BAMP-1 was similar to that of human apolipoprotein A-II (apo A
      II), a major component of high-density lipoprotein (HDL), and the amino acid
      composition was almost identical to that of a previously reported candidate for
      bovine apo A-II. BAMP-1 was recovered from the post-HDL fraction, but not from
      the HDL fraction of the serum and was associated with a small amount of
      triglycerides (5%, w/w). These results suggest that BAMP-1 is the bovine
      homologue of apo A-II and is present in almost free form in serum. BAMP-1 showed
      a weak growth-inhibitory activity against Escherichia coli and yeasts tested in
      phosphate-buffered saline (PBS).

PMID- 9538261
TI  - Effect of glycerol on the affinity of DnaA protein for ATP in the presence of
      cardiolipin.
AB  - Acidic phospholipids, such as cardiolipin, decrease the affinity of DnaA protein
      for adenine nucleotides and can activate the inactive form of DnaA protein in
      vitro. In this study, we examined the effect of glycerol on the affinity of DnaA
      protein for ATP in the presence of cardiolipin. High concentrations of glycerol
      (34%) restored the affinity of DnaA protein for ATP, which was decreased by
      cardiolipin. Glycerol inhibited the binding of cardiolipin with DnaA protein.
      Glycerol had little effect on membrane fluidity, which is essential for the
      interaction between cardiolipin and DnaA protein, whereas it increased the Kd
      value of DnaA protein for ATP in the absence of cardiolipin. These results
      suggest that glycerol causes DnaA protein to become insensitive as to the
      interaction with cardiolipin by changing the conformation of the protein without
      altering the physical nature of the phospholipid.

PMID- 9538262
TI  - Comparison of in vivo activities of 5'-connected and 3'-connected cis-acting
      ribozymes: selection of intracellularly active ribozymes using the gene for
      dihydrofolate reductase (DHFR) as a selective marker in Escherichia coli.
AB  - If ribozymes are to be exploited in vivo, it is necessary to select ribozymes
      that are functional in the intracellular environment. Ribozymes selected in the
      intracellular environment should retain their function in vivo as well as in
      vitro. We have devised a novel system for selection of active ribozymes from
      pools of active and inactive ribozymes using the gene for dihydrofolate reductase
      (DHFR) as a selective marker. In our first attempt, a sequence encoding either an
      active or an inactive ribozyme was connected upstream of the gene for DHFR. Each
      plasmid was designed such that, when the ribozyme was active, the ribozyme would
      cleave the target site and, as a result, the rate of production of DHFR would be
      high enough to endow resistance to trimethoprim (TMP). However, a critical defect
      may be associated with introduction of a ribozyme upstream of the DHFR gene
      because, during actual screening for active ribozymes on the 5' side from a pool
      of random sequences, there is the danger of selecting sequences that are not
      related to the activity of ribozymes. Indeed, some upstream linker sequences
      affected the level of expression of the DHFR protein and, as a result, the
      resistance of Escherichia coli to TMP. Therefore, we newly constructed a 3'
      connected ribozyme system, and activities in vivo of 5'-connected and 3'
      connected ribozymes were compared. We found that the cleavage efficiencies in
      vivo were nearly identical for the two types of ribozyme, 24% for the 5'-side
      ribozyme and 23% for the 3'-side ribozyme, indicating that polysomes did not seem
      to inhibit the action of the 3'-connected ribozyme. In both cases, when cells
      were transformed with a 1 : 1 mixture of active and inactive ribozyme-coding
      plasmids, it was mainly the cells that harbored the active ribozyme that survived
      in the presence of TMP.

PMID- 9538263
TI  - Functional expression and enzymatic properties of two Sitophilus zeamais cysteine
      proteinases showing different autolytic processing profiles in vitro.
AB  - To characterize in more detail the cathepsin L-like cysteine proteinases from
      Sitophilus zeamais (SCPs) cloned in our previous study [Matsumoto et al. (1997)
      J. Biochem. 121, 464-476], we established a system for their functional
      expression and purification using a glutathione S-transferase (GST) fusion gene
      vector from Escherichia coli. The proenzyme forms of two representative SCPs,
      proSCPc1 and proSCPg3, were expressed as GST-fusion proteins and purified on a
      glutathione Sepharose column. GST-proSCPc1 undergoes autoproteolytic cleavage
      into the mature form efficiently at acidic pH, and exhibits significant
      proteolytic activity toward various substrates including hemoglobin and Z-Phe-Arg
      MCA. The enzymatic characteristics of the activated form of SCPc1 are similar to
      those of mammalian cathepsin L, but its pH optimum for the hydrolysis of
      hemoglobin is significantly lower. The other proSCP, GST-proSCPg3, which has a
      shorter COOH-terminal domain than SCPc1, undergoes almost no autolytic processing
      and shows only very slight proteolytic activity, although the other enzymatic
      characteristics of GST-proSCPg3 are similar to those of GST-proSCPc1.

PMID- 9538264
TI  - Bovine spleen cathepsin A: characterization and comparison with the protective
      protein.
AB  - Cathepsin A was purified approximately 550-fold with an overall yield of 4% from
      bovine spleen crude extracts by successive chromatographies on DEAE-Sephadex A
      50, phenyl-Toyopearl 650C, and Con A-agarose. PAGE of the purified enzyme without
      2-mercaptoethanol revealed an apparent molecular size of 110 kDa, and SDS-PAGE
      with 2-mercaptoethanol gave two polypeptide bands corresponding to 32 and 25 kDa
      and without 2-mercaptoethanol a single polypeptide 52 kDa band. These results
      indicate that the enzyme has an (alpha beta)2 tetrameric structure in which the
      alpha (32 kDa) and beta (25 kDa) subunits are linked by disulfide bond(s). The
      enzyme exhibited peptidase activities, hydrolyzing various Z-dipeptides with
      optimum pHs between 5.0 and 5.8. The hydrolytic rate for Z-Phe-Ala was 15 times
      higher than that for Z-Glu-Tyr, the traditional cathepsin A substrate. The enzyme
      also catalyzed the hydrolysis of the C-terminal amino acids of RCM-RNase A and
      showed esterase activity toward BTEE at pH around 7.5. DFP and TPCK completely
      inhibited both peptidase and esterase activities, and [1,3-3H]DFP was bound to
      the alpha subunit. All these results support the fact that the enzyme is a serine
      carboxypeptidase. The N-terminal amino acid sequences of the alpha and beta
      subunits are highly homologous to those of the human protective protein in
      galactosialidosis, strongly supporting the identity between cathepsin A and the
      protective protein.

PMID- 9538265
TI  - Comparison of survival-promoting effects of brain-derived neurotrophic factor and
      neurotrophin-3 on PC12h cells stably expressing TrkB receptor.
AB  - We obtained two PC12h cell lines, PC-pAB1 and PC-pAB2, stably expressing TrkB
      receptor and investigated the effects of BDNF and NT-3 in these cell lines. The
      cells differentiated into neuron-like cells in response to BDNF as well as NGF,
      neurite extension being more rapid in the former case. These TrkB-expressing
      cells also extended neurites in response to NT-3, which is a nonpreferred ligand
      of TrkB. Next, we examined the survival-promoting effects of NGF, BDNF, and NT-3
      under apoptotic conditions of oxygen toxicity in naive cells and NGF deprivation
      in differentiated cells. In both cases, BDNF prevented cell death similarly to
      NGF. NT-3 prevented cell death induced by oxygen toxicity in naive cells, but not
      that induced by NGF deprivation in differentiated cells. NT-3 induced the
      tyrosine phosphorylation of TrkB in naive cells, but not in differentiated cells.
      These results indicate that NT-3 has survival-promoting effects on naive TrkB
      expressing PC12h cells, but not on differentiated cells because of its inability
      to induce the tyrosine phosphorylation of TrkB.

PMID- 9538266
TI  - Synthesis of artificial glycoconjugate polymers starting from enzymatically
      synthesized oligosaccharides and their interactions with lectins.
AB  - Styrene derivatives substituted with N-linked beta-anomeric oligosaccharides were
      synthesized via a simple two-step procedure starting from three enzymatically
      prepared oligosaccharides: N-acetyllactosamine (Galbeta1-4GlcNAc), N
      acetylisolactosamine (Galbeta1-6GlcNAc), and 4'-galactosyllactose (Galbeta1
      4Galbeta1-4Glc). Their homo- and copolymerization with acrylamide using 2,2'
      azobisisobutyronitrile as an initiator in dimethyl sulfoxide at 60 degreesC gave
      the corresponding glycopolymers. Binding between glycopolymers and lectins was
      investigated by means of hemagglutination inhibition experiments. The inhibition
      of RCA120 lectin-induced hemagglutination by N-acetyllactosamine-carrying
      homopolymer was about 10(3) times stronger than that of the oligosaccharide
      itself. The enhanced binding capacity with lectins can be explained in terms of a
      multivalent or cluster effect along the polymeric chain. In some combinations
      between lectins and polymers, the copolymers inhibited hemagglutination more
      strongly than the homopolymers did. N-Acetyllactosamine-carrying glycopolymer
      showed about 3 x 10(3) times weaker inhibition of DSA lectin-induced
      hemagglutination than the different type of N-acetyllactosamine-carrying
      glycopolymer which has an O-linked beta-anomeric phenyl aglycon of each repeating
      unit along a polyacrylamide backbone.

PMID- 9538267
TI  - Identification of the protein import components of the rat mitochondrial inner
      membrane, rTIM17, rTIM23, and rTIM44.
AB  - We cloned rat liver mitochondrial 18.1, 21.9, and 51.0 kDa proteins with a
      significant structural homology to the components of the translocase of the yeast
      mitochondrial inner membrane, Tim17, Tim23, and Tim44. The 18.1 and 21.9 kDa
      proteins were synthesized as mature forms having four potential transmembrane
      segments and localized to the mitochondrial inner membrane. The 51.0 kDa protein
      is a precursor having a presequence of approximately 6 kDa which is cleaved
      during import into the mitochondria. The mature 45 kDa protein is located in the
      matrix, both in a soluble form and in a membrane-bound, alkali-extractable form.
      Immunofluorescence microscopy confirmed the location of all three proteins in the
      mitochondria. Antibodies against the 21.9 kDa protein, but not those against the
      18.1 and 51.0 kDa proteins, inhibited the precursor import into the mitoplasts in
      vitro. Immunoprecipitation indicated that all three proteins interacted with the
      protein in transit to the matrix. Immunoprecipitation also revealed that the 18.1
      kDa protein formed a complex with the 21.9 kDa protein and the 45 kDa protein
      with mHsp70; the latter complex was dissociated in an ATP- or ADP-dependent
      manner and the reaction was impeded by AMP-PNP or inorganic phosphate. These
      assays thus demonstrated the 18.1, 21.9, and 45 kDa proteins to be the
      translocator components of the rat mitochondrial inner membrane and, therefore,
      the functional homologues of Tim17, Tim23, and Tim44, respectively.

PMID- 9538268
TI  - Tumor necrosis factor-alpha regulates the gene expression of macrophage migration
      inhibitory factor through tyrosine kinase-dependent pathway in 3T3-L1 adipocytes.
AB  - Macrophage migration inhibitory factor (MIF) has been rediscovered as a
      proinflammatory cytokine, pituitary hormone, and glucocorticoid-induced
      immunoregulator. We have recently identified the expression of MIF in adipocytes
      and found that tumor necrosis factor (TNF)-alpha stimulates its secretion from
      3T3-L1 adipocytes. Since adipocytes are regarded as a potential source of various
      biologically active substances, we examined in more detail the effect of TNF
      alpha on MIF expression in 3T3-L1 adipocytes in the present study. We found that
      TNF-alpha induced MIF mRNA in dose- and time-dependent manners. After stimulation
      with TNF-alpha, the amount of intracellular MIF protein was unchanged or slightly
      decreased, concomitant with increased release of this protein into the
      extracellular space. This observation indicates that TNF-alpha stimulates MIF
      secretion from the constitutively expressed intracellular pool of 3T3-L1
      adipocytes and promotes de novo synthesis of MIF. From evaluation of the
      mechanism of MIF gene expression, we found that tyrosine kinase inhibitors,
      either genistein or herbimycin A, suppressed the MIF mRNA induction by TNF-alpha.
      The results suggest the possibility that upregulation of MIF mRNA expression by
      TNF-alpha is mediated by a tyrosine kinase-dependent pathway. Taken together, the
      present observations shed light on the role of MIF in the metabolism of obesity
      and diabetes.

PMID- 9538269
TI  - Molecular cloning, expression, and enzymatic characterization of rabbit
      hydroxysteroid sulfotransferase AST-RB2.
AB  - Cytosolic sulfotransferases, which consist of at least three gene families, play
      a major role in activation and detoxification of both endogenous and exogenous
      chemicals. We recently purified a rabbit sulfotransferase, AST-RB2, showing high
      activities to both hydroxysteroids and amines. To characterize this enzyme, a
      rabbit cDNA library was screened using anti-AST-RB2 antibodies. The isolated cDNA
      was judged to encode AST-RB2 (ST2A8) based on the amino acid sequences of peptide
      fragments obtained from purified AST-RB2. The cDNA showed high similarity to
      other mammalian hydroxysteroid sulfotransferases (ST2) at the amino acid level
      (58-68%), but low similarity to aryl sulfotransferases (ST1) (less than 37%). The
      protein expressed in Escherichia coli catalyzed sulfation of typical ST2
      substrates. Therefore, ST2A8 was judged to belong to the ST2 family from both its
      primary structure and substrate specificity. The ST2A8 protein expressed in E.
      coli clearly differed from rat ST2A1 and ST2A2 on its localization
      (cytosol/insoluble fraction ratio). ST2A8 had no activity to lithocholate, but
      showed the highest catalysis on dehydroepiandrosterone and testosterone among the
      four forms (ST2A1, ST2A2, ST2A3, and ST2A8), indicating a clear difference
      between ST2A forms in substrate specificity to endogenous chemicals.

PMID- 9538270
TI  - Regio- and stereoselectivity in propranolol metabolism by dog liver microsomes
      and the expressed dog CYP2D15.
AB  - We have studied the regio- and stereoselectivity of ring-hydroxylation and N
      desisopropylation of S(-)- and R(+)-propranolol, using dog liver microsomes and
      the expressed dog CYP2D15 in insect cells. In dog liver microsomes, 4
      hydroxylation was the preferred pathway in S(-)-propranolol oxidation, while N
      desisopropylation was the preferred pathway in R(+)-propranolol oxidation. S(-)
      Propranolol was preferred over R(+)-propranolol as substrate for 4- and 5
      hydroxylations, while R(+)-propranolol was the preferred substrate for N
      desisopropylation at higher substrate concentrations. The expressed CYP2D15 had
      high catalytic activities toward 4-, 5-hydroxylation, as well as N
      desisopropylation of both enantiomers. At the substrate concentrations used, 4
      hydroxylation was the preferred pathway for the metabolism of both enantiomers,
      and S(-)-propranolol was the preferred substrate over R(+)-propranolol for all
      three monooxygenations catalyzed by CYP2D15. Anti-CYP2D15 peptide antibody
      strongly inhibited 4- and 5-hydroxylation of both enantiomers in dog liver
      microsomes, while it did not inhibit their N-desisopropylation. These findings
      suggest that CYP2D15 is highly responsible for the stereoselective 4- and 5
      hydroxylations of propranolol in dog liver microsomes.

PMID- 9538271
TI  - Fluorescence microscopic demonstration of cathepsin K activity as the major
      lysosomal cysteine proteinase in osteoclasts.
AB  - The enzyme activity of lysosomal cysteine proteinases in vital rabbit osteoclasts
      and mouse osteoclast-like cells was visualized with Z-Leu-Arg-4-methoxy-beta
      naphthylamide (Z-LR-MNA) as the enzyme substrate. The MNA liberated by
      proteolysis forms a fluorescent insoluble Schiff-base product in the presence of
      5-nitrosalicylaldehyde. Many small fluorescent particles, endproducts of the Z-LR
      MNA hydrolysis, were observed in proximity to the bone surface underneath the
      actively resorbing osteoclasts, as well as in the cytoplasm. The Z-LR-MNA
      hydrolase activity was markedly diminished by bafilomycin A1 and chloroquine
      treatment. Moreover, the activity was completely inhibited by cysteine proteinase
      inhibitors such as leupeptin and E-64d, but not by other classes of proteinase
      inhibitors. About 60% of the hydrolase activity in mouse osteoclast-like cells
      was immunoabsorbed by anti-cathepsin K antibody-coupled Sepharose CL-4B beads,
      and about 10% of the activity was absorbed with the anti-cathepsin L antibody
      coupled beads. Thus, the majority of the Z-LR-MNA hydrolase activity in
      osteoclasts was derived from cathepsin K. In contrast, using the same substrate
      in the assay, no detectable cathepsin K activity was observed in mouse peritoneal
      macrophages. The abundant cathepsin K activity in osteoclasts would therefore
      indicate a significant role of this enzyme in bone matrix degradation.

PMID- 9538272
TI  - Presence of conserved domains in the C-terminus of MARCKS, a major in vivo
      substrate of protein kinase C: application of ion trap mass spectrometry to the
      elucidation of protein structures.
AB  - MARCKS, the major protein kinase C substrate in various cells and tissues, binds
      to calmodulin, acidic membrane phospholipids, and actin filaments, and these
      interactions are regulated by protein phosphorylation. We have previously
      analyzed MARCKS purified from bovine brain using capillary liquid
      chromatography/electrospray mass spectrometry and found that the protein
      structure differed significantly from that deduced from cDNA sequences
      [Taniguchi, H., Manenti, S., Suzuki, M., and Titani, K. (1994) J. Biol. Chem.
      269, 18299-18302]. Moreover, the alignment of the protein from various species
      showed a lack of any conserved sequences in the C-terminal half of the molecule.
      This prompted us to reexamine the C-terminal amino-acid sequence of bovine
      MARCKS. The purified protein was digested with lysyl endoprotease, and the
      obtained C-terminal peptide was further digested with either Staphylococcus V8
      protease or NTCB. The small peptides thus obtained were analyzed by liquid
      chromatography/electrospray/tandem mass spectrometry. This combined with gas
      phase Edman sequencing allowed us to determine the C-terminal primary structure.
      The sequence obtained differed significantly from that reported previously, and
      the comparison with other species revealed the presence of a novel conserved
      domain in the C-terminal region of MARCKS.

PMID- 9538273
TI  - Motor control for bilateral muscular contractions in humans.
AB  - This article briefly reviews neural mechanisms responsible for bilateral
      simultaneous muscular contractions by analyzing force outputs and their
      underlying electromyogram (EMG) and electroencephalographic (EEG) activities. Two
      major issues were addressed from a series of studies concerning maximal and
      submaximal (20% of maximal voluntary contraction) bilateral contractions (i.e.,
      mechanisms for the bilateral strength deficit and common drive). It is suggested
      that: (1) during maximal bilateral contractions there exists a common drive from
      the central nervous system to the right and left muscles and the bilateral
      strength deficit is due to the decreased neural activations of the precentral
      motor cortex of both hemispheres; and (2) during bilateral contractions at
      submaximal level, a common drive also exists for simultaneous use of homologous
      muscles and the submaximal bilateral contraction is coordinated mainly under the
      control of the left hemisphere for right-handed people.

PMID- 9538274
TI  - Hormonal and osmotic regulation of NaCl transport in renal distal nephron
      epithelium.
AB  - One of the most important factors controlling blood pressure is the total body
      Na+ content, which depends upon Na+ intake and excretion. The kidney influences
      body Na+ content by regulating the tubular absorption of the Na+ filtered through
      the glomeruli. Thus, the regulation of Na+ absorption in the tubules of the
      kidney plays an important role in controlling blood pressure. More than 99% of
      the Na+ passing through the glomerulus is reabsorbed in the kidney. About 90% of
      the filtered Na+ through the glomerulus is reabsorbed in the proximal tubule and
      the ascending limb of the loop of Henle. The remainder of the Na+ absorption
      occurs in the distal nephron. This process is regulated by hormones such as
      aldosterone and antidiuretic hormone (ADH), and also by the osmolality of the
      plasma. These observations suggest that the regulation of Na+ transport in the
      distal nephron by hormones and osmolality plays an important role in the control
      of blood pressure. The distal nephron is composed of two different types of
      epithelial cells: the principal cell and the intercalated cell. The latter is
      also composed of two types of cells: alpha and beta intercalated cells. In
      addition to Na+ absorption, the distal-nephron epithelial cells also participate
      in K+ and H+ secretion. Na+ absorption is mediated through the principal cell,
      which also contributes to K+ secretion, whereas H+ is secreted through both types
      of intercalated cells, alpha and beta, in different ways. There are, in general,
      two steps in the transepithelial ion movement across the epithelium, including
      the distal-nephron epithelium. For example, in the case of Na+ absorption, one is
      the entry step of Na+ across the apical membrane and the other is the extrusion
      step of Na+ across the basolateral membrane. This means that there are two major
      regulatory sites of transepithelial Na+ absorption: namely, regulation of the
      entry and extrusion steps of Na+. It is generally thought that the entry step of
      Na+ across the apical membrane is the rate-limiting step in the transepithelial
      Na+ transport and that Na+ channels in the apical membrane play an important role
      as an entry step of Na+ and are regulated by hormones and plasma osmolality. In
      this review, we describe the regulatory mechanisms of Na+ absorption in renal
      distal-nephron epithelium by aldosterone, ADH and osmolality. Further, we will
      review the regulatory mechanisms of Cl- transport, which also plays an important
      role in Na+ transport as a major counter ion, and discuss other roles of Cl- in
      the active regulation of Na+ transport.

PMID- 9538275
TI  - Chronic cold exposure stimulates microvascular remodeling preferentially in
      oxidative muscles in rats.
AB  - The effects of 4-week cold exposure on capillary geometry, particularly in terms
      of the distribution of arteriolar and venular capillaries and their capillary
      domain areas, were studied for different types of skeletal muscles in male Wistar
      rats. Morphological data for capillaries and muscles were obtained from muscle
      cross-sections exposed to a double-staining method that distinguishes arteriolar
      portions from venular portions of capillaries. In soleus (SOL; type I fibers) and
      the deep portion of gastrocnemius (GASd; type I and IIa fibers) muscles, total
      capillary density and density of arteriolar capillary were significantly greater
      in cold-acclimated (CA) rats than in warm control (WC) rats (p < 0.05). In the
      superficial portion of the gastrocnemius (GASs; type IIb fibers), however, these
      changes in capillarity were not observed. After cold acclimation, fiber cross
      sectional area was significantly decreased by 21, 28 and 15% in SOL, GASd and
      GASs (p < 0.05), respectively. In SOL and GASd but not in GASs, capillary domain
      areas of arteriolar, intermediate and venular portions in CA were significantly
      smaller than those of the respective portions in WC (p < 0.05). Succinate
      dehydrogenase activity was significantly increased after cold acclimation, by 31%
      in SOL and 21% in GASd (p < 0.05). In GASs, however, the activity remained
      unchanged after cold acclimation. These results suggest that adaptive changes in
      the oxygen transport system were observed after cold acclimation in the skeletal
      muscles that are mainly composed of oxidative fibers. These adaptive changes may
      improve the effective oxygen supply to muscle tissues that contribute to
      thermogenesis in a cold atmosphere.

PMID- 9538276
TI  - Ryanodine decreases internal Ca2+ recirculation fraction of the canine heart as
      studied by postextrasystolic transient alternans.
AB  - We tested our hypothesis that the O2 wasting of Ca2+ handling in the excitation
      contraction (E-C) coupling in ryanodine-treated failing hearts could be reflected
      by a decrease in the internal Ca2+ recirculation fraction (RF). We have reported,
      using canine excised cross-circulated hearts, that intracoronary ryanodine (40
      nmol/l blood) halved left ventricular contractility without decreasing myocardial
      O2 consumption for the E-C coupling. We previously suspected this
      mechanoenergetic state to manifest energy wasting of Ca2+ handling due to
      ryanodine causing leakage of Ca2+ from the sarcoplasmic reticulum. To test this
      hypothesis, we analyzed all the sporadic spontaneous cases of postextrasystolic
      potentiation (PESP) obtained during the ryanodine experiments. We calculated RF
      from the beat constant of the exponential decay component of not only the
      monotonic type but also the transient alternans type of PESP. Results showed that
      ryanodine significantly decreased the beat constant in both types of PESP from
      about 2 to 1.5 beats and hence RF from 0.6 to 0.5 on the average, supporting the
      hypothesis. This organ-level systems approach to Ca2+ handling using transient
      alternans PESP as well as monotonic PESP may help obtain better insights into the
      mechanoenergetics of failing hearts.

PMID- 9538277
TI  - Metabolism and acid-base status during hypoxic ventilatory depression.
AB  - The ventilatory response to acute systemic hypoxia has been thought to be
      determined by the balance between hypoxic stimulation via peripheral
      chemoreceptors and hypoxic inhibition of the respiratory neurons. In moderate
      severe hypoxia, the latter predominates the former resulting in ventilatory
      "depression" (HVD). However, ventilation relative to metabolic rate (V.O2) during
      HVD is "not depressed" but remains increased because of associated reduction in
      O2 uptake (V.O2). The experiment presented here was conducted to elucidate the
      changes in CO2 output (V.CO2) and acid-base status during hypoxia and their role
      in ventilatory regulation. Ventilation, metabolic rate (V.O2, V.CO2), acid-base
      status and blood lactate concentration were measured during and after inhalation
      of hypoxic gases in halothane-anesthetized and spontaneously breathing rats. The
      HVD occurred at FIO2 0.08 with increased blood lactate concentration, increased
      venous PCO2 and a large drop in venous pH without significant changes in arterial
      pH and PCO2. Furthermore, the amount of reduction in V.CO2 during HVD was much
      smaller than that of V.O2 and the V.CO2/V.O2 ratio increased. These findings
      suggest that CO2 output becomes relatively higher than O2 consumption in moderate
      severe hypoxia. The possible origin of CO2 accumulation in the venous blood, such
      as the buffering of lactic acid by bicarbonate, and its role in ventilatory
      stimulation are discussed. Since there was no large increase in V.E and metabolic
      rate in the post-hypoxic period, "O2 debt" during HVD was small.

PMID- 9538279
TI  - Decremental oscillation curve fitting of heart rate response following face
      immersion into cold water.
AB  - Using 18 healthy volunteers, we attempted to fit the heart rate response to a
      decremental oscillation curve by the least-squares method following facial
      immersion into cold water. The decremental oscillation equation was as follows:
      HR = alpha.e(-betat) sin omegat + gamma, where HR is the instantaneous heart rate
      at t s, alpha the maximum amplitude of the decremental oscillation, beta the
      decremental rate, omega the angular velocity and gamma the basal heart rate. Each
      subject immersed his/her face fully in a basin filled with ice-cold water (4
      degrees C) for 30 s. The heart rate response to facial immersion was
      significantly fitted to the decremental oscillation curve with a correlation
      coefficient > 0.75 in all the trials. Double trials with a 15-min intertrial
      interval did not show any significant change in the coefficients. Atropine
      sulfate decreased the value of coefficient omega and increased that of gamma but
      did not change alpha or beta, indicating that omega is determined mainly by
      parasympathetic tone. There were no differences for any coefficient between men
      and women. The coefficients beta and gamma increased in association with age.
      Given the significant fitting to the decremental oscillation curve of the heart
      rate response, we propose that the corresponding electrical circuit consists of a
      resistance and an inductor connected in series, with a condenser in a parallel
      circuit with a direct current impulse. This method of fitting with the
      corresponding electric circuit may be useful for analysis of the heart rate
      response to physiological stimulus.

PMID- 9538278
TI  - Effects of transient coronary occlusion on the capillary network in the left
      ventricle of rat.
AB  - The objective was to examine the changes in the capillary network in the left
      ventricle of rats subjected to transient occlusion of the left coronary artery
      followed by reperfusion (I-R). Eighteen Wistar rats were divided into three
      groups and all rats were anaesthetized with ethyl ether and artificially
      ventilated. The I-R 1 rats were subjected to a 3 min occlusion followed by
      reperfusion; the I-R 3 rats had three 3 min occlusions separated by 3 min of
      reperfusion; the Sham-operated rats underwent surgery but the coronary artery was
      not occluded. The thorax was closed at the end of the procedures and the rats
      were sacrificed for isolation of the hearts 30 d after treatment. Frozen sections
      of the left ventricles were cut and differential staining was used to classify
      the capillary portions. Five additional rats treated as the I-R 1 group were
      sacrificed at 120 min after reperfusion. Their left ventricles were used for
      immunohistochemical investigation of the early expression of bFGF and VEGF. By
      comparison with the Sham-operated rats, both I-R groups showed increases in the
      capillary density of total and venular capillary portions, an increased capillary
      : myocyte (C : M) ratio and a decrease in the capillary domain area in the three
      capillary portions. The changes in the I-R 1 group were significantly greater
      than those in the I-R 3 group, suggesting that the frequent experience of
      ischemic attack reduces the capacity of angiogenesis. In the rats sacrificed 120
      min after the start of reperfusion, bFGF and VEGF were expressed on capillaries
      and in some myocytes. Punctate bFGF or VEGF staining was observed even 30 d after
      the transient ischemia. One 3 min occlusion of the left coronary artery followed
      by reperfusion produced changes in capillarity that would increase the oxygen
      supply to ventricular tissues. These effects may be attributed to the bFGF and
      VEGF expressed around capillaries. Repeated occlusions interspersed with a short
      period of reperfusion reduced the advantageous effects on capillarity.

PMID- 9538280
TI  - Hypotonically induced whole-cell currents in A6 cells: relationship with cell
      volume and cytoplasmic Ca2+.
AB  - We investigated changes in whole-cell currents, cell volume, and intracellular
      calcium concentration ([Ca2+]i) during hypotonic stimulation in whole-cell
      clamped cultured amphibian renal cells (A6 cells). Upon being exposed to
      hypotonic solution (80% osmolality), the A6 cells swelled and peaked in the first
      5 min, which was followed by a progressive decrease in cell volume termed
      regulatory volume decrease (RVD). Following the cell swelling, there were large
      increases in both outward- and inward-currents, which seemed to be carried by K+
      efflux and Cl- efflux, respectively. A K+ channel blocker (TEA or quinine) or a
      Cl- channel blocker (NPPB or SITS) significantly inhibited both currents and RVD,
      suggesting that the inward- and outward-currents are highly correlated with each
      other and essential to RVD. Hypotonic stimulation also induced a transient
      [Ca2+]i increase, of which the time course was essentially similar to that of the
      currents. When internal and external Ca2+ were deprived to eliminate the Ca2+
      transient increase, whole-cell currents and RVD were strongly inhibited. On the
      other hand, channel blockers TEA and NPPB, which inhibited whole-cell currents
      and RVD, did not inhibit the [Ca2+]i increase. It is concluded that hypotonic
      stimulation to A6 cells first induces cell swelling, which is followed by [Ca2+]i
      increase that leads to the coactivation of K+ and Cl- channels. This coactivation
      may accelerate K+ and Cl- effluxes, resulting in RVD.

PMID- 9538281
TI  - Effect of lipophilic ions on the intramembrane charge movement and intracellular
      Ca2+ release in fetal mouse skeletal muscle cells.
AB  - The effects of lipophilic ions on the intramembrane charge movement and
      intracellular calcium transient were studied using freshly dissociated skeletal
      muscle cells from mice fetuses. The lipophilic cations Rhodamine 6G and
      tetraphenylphosphonium (TPP) immobilized part of the intramembrane charge
      movement in a dose-dependent manner, and inhibited both calcium transient and
      contraction evoked by membrane depolarization. In contrast, the lipophilic anion
      1-anilinonaphthalene-8-sulfonic acid (ANS) had no effect on intramembrane charge
      movement. We suggest that the lipophilic cations block the voltage-sensing
      mechanism for the excitation-contraction (E-C) coupling mechanism.

PMID- 9538282
TI  - High-pressure-induced hemolysis of hereditary spherocytic erythrocytes is not
      suppressed by DIDS labeling.
AB  - Hemolytic properties of human erythrocytes in hereditary spherocytosis (HS) were
      examined under hydrostatic pressure or hypotonic conditions. In the hypotonic
      buffer, HS erythrocytes were more fragile than normal erythrocytes, and the
      osmotic fragility was similarly enhanced if both erythrocytes were treated with
      4,4'-diisothiocyanostilbene-2,2'-disulfonate (DIDS), an anion transport
      inhibitor. On the other hand, the hemolysis of HS erythrocytes at 200 MPa was
      almost the same degree as that of normal cells. Upon DIDS treatment, the
      hemolysis of normal erythrocytes at 200 MPa was suppressed by about 35%, whereas
      that of HS erythrocytes was not affected. The absence of a suppressive effect of
      DIDS on high-pressure-induced hemolysis is likely to be HS-specific and may be a
      reflection of the underlying defects of band 3-cytoskeleton interactions in HS
      erythrocytes.

PMID- 9538283
TI  - Basolateral pH-sensitive K+ channels mediate membrane potential of proximal
      tubule cells in bullfrog kidney.
AB  - The present study investigated basolateral K+ channels and their pH-sensitivity
      in isolated bullfrog proximal tubule cells by using the patch-clamp technique,
      and compared channel activity with the basolateral membrane potential (EM) and
      intracellular pH (pHi) monitored by using double-barreled H+-selective
      microelectrodes in perfused bullfrog proximal tubules. In the patch-clamp
      experiments, K+ channels with inward slope conductance of about 50 pS were
      observed in the basolateral membrane of isolated proximal tubule cells in cell
      attached patches. Raising pH of the bath with HCO3(-)-free HEPES Ringer solutions
      from 7.7 (control) to 8.2 in the presence of an H+ ionophore, FCCP (2 micro M),
      enhanced channel activity to 126.4% of controls; lowering bath pH to 7.2 and to
      6.7 reduced channel activity to 26.4 and to 1.7% of controls. Microelectrode
      experiments in bullfrog proximal tubules perfused with HCO3(-) -free HEPES Ringer
      solutions showed that EM and pHi in control conditions of peritubular pH 7.7
      without FCCP were -52.6 mV and 7.45. Raising peritubular pH to 8.2 in the
      presence of FCCP (2 micro M) increased EM and pHi to -61.8 mV and 7.73; lowering
      it to 7. 2 and to 6.7 decreased EM and pHi to -28.6 mV and 7.25 and to -10.6 mV
      and 6.95. These results suggest that changes in EM in response to cellular
      alkalinization or acidification made by HCO3(-)-free HEPES solutions are produced
      primarily by changes in activity of the pH-sensitive K+ channels.

PMID- 9538284
TI  - Effects of hypothermia and aging on postischemic reperfusion in rat eyes.
AB  - The acute changes in choroidal blood flow during postischemic reperfusion were
      investigated by using laser Doppler flowmetry in young (4 months) and aged (more
      than 18 months) Wistar rats under normothermic and hypothermic conditions.
      Choroidal blood flow was measured by using a laser Doppler probe attached to the
      scleral surface before, during, and after temporary ischemia produced by an
      elevation of intraocular pressure up to 80 mmHg. Body temperature was maintained
      either from 38 to 39 degrees C (normothermia) or from 30 to 33 degrees C
      (hypothermia). Under the normothermic condition, postischemic reperfusion showed
      hyperperfusion dominantly in all groups (117.1 +/- 4.9% of the baseline value
      after 10 min of ischemia, 208.6 +/- 16.1% after 30 min, and 176.6 +/- 17.1% after
      50 min). Exposure to hypothermia attenuated the postischemic hyperperfusion
      (101.9 +/- 11.7% after 10 min of ischemia, 152.9 +/- 11.2% after 30 min, and
      107.8 +/- 19.9% after 50 min). In aged rats, the response of choroidal blood flow
      during reperfusion was variable. The no-reflow phenomenon was observed in 1 of 5
      rats, marked hyperperfusion (238 and 177%) in 2 rats, and a small magnitude (127
      and 115%) of hyperperfusion in the other 2 rats, whereas marked hyperperfusion
      was observed in all rats of the young group after 30 min of ischemia. These
      results suggest that hyperperfusion is dominant during the acute phase of
      postischemic reperfusion in young rats under normothermia. Hypothermia attenuates
      the postischemic hyperperfusion of the choroidal blood flow. The circulatory
      response during postischemic reperfusion becomes variable with age.

PMID- 9538285
TI  - Relationship between maximal pulmonary ventilation and arterialized venous blood
      potassium and dopamine concentrations obtained at exhaustion in man.
AB  - This study was performed to test the hypothesis that potassium concentration in
      arterialized blood may be closely related to maximal pulmonary ventilation
      (V.Emax) obtained at exhaustion during maximal exercise in man. Eleven healthy
      men performed bicycle exercise with incremental loading at 60 rpm until
      exhaustion. Pulmonary ventilation (V.E), oxygen uptake (V.O2), and heart rate
      (HR) were determined continuously throughout the experiment. Arterialized venous
      blood samples were collected to measure potassium ([K+]), lactate ([La]),
      hydrogen ion (pH), catecholamine ([CA]), and dopamine ([DA]) concentrations. A
      significant correlation (r = 0.98-0.88) between V.E and [K+], [La], and pH during
      exercise was observed in all subjects. Furthermore, a close relationship was
      found in this study between dopamine concentration measured at exhaustion ([DA]0)
      and maximal pulmonary ventilation per kilogram of body weight (V.Emax/W) (r = 
      0.668, p < 0.05) or maximum oxygen uptake per kilogram of body weight (VO2MAX/W)
      (r = 0.720, p < 0.05). However, no significant correlation was found between V.
      Emax/W and [K+]0 (r = 0.202, NS), [La]0 (r = -0.096, NS), and pH0 (r = 0.344,
      NS). These results suggest that dopamine may play a more important role in the
      determination of maximal pulmonary ventilation during exercise in man than K+ or
      pH.

PMID- 9538286
TI  - Measurement of intraocular pressure by both invasive and noninvasive techniques
      in rabbits exposed to head-down tilt.
AB  - This study investigates changes in intraocular pressure (IOP) in rabbits during
      head-down tilt (HDT), which is commonly used as an experimental model to simulate
      microgravity. IOP was measured by the needle insertion technique (IOPNEEDLE) and
      Tono-pen tonometry (IOPTONO-PEN). Although the absolute value of the IOPTONO-PEN
      was significantly smaller than that of the IOPNEEDLE, a significant correlation
      (r = 0.99) was observed between them. A linear regression analysis yielded an
      equation as follows: IOPTONO-PEN = 0. 67 IOPNEEDLE - 0.67. Both the IOPNEEDLE and
      the IOPTONO-PEN changed depending on the tilt angle. Tilting from horizontal (0
      degrees) to 75 degrees head-down increased the IOPNEEDLE and the IOPTONO-PEN by
      7.3 +/- 0.8 (mean +/- SEM) mmHg and 4.4 +/- 1.3 mmHg. The IOPNEEDLE elevated from
      13.1 +/- 1.3 to 16.9 +/- 1.0 mmHg immediately after the onset of 45 degrees HDT
      and then gradually declined. The value of the IOPNEEDLE during 8 h of HDT was
      significantly higher than the value in the control animals, which were kept at
      the horizontal prone position throughout the experiment. Similar findings were
      observed in the IOPTONO-PEN. These results suggest that the needle insertion
      technique and the Tono-pen tonometry are both useful for measuring IOP in
      rabbits.

PMID- 9538287
TI  - Does electrical stimulation of the sciatic nerve prevent suspension-induced
      changes in rat hindlimb bones?
AB  - Osteoporosis due to mineral loss is a major health problem resulting from long
      term spaceflight. The development of a suitable countermeasure is essential
      because an advanced decrease in bone density could be irreversible. Therefore the
      current study was performed to test our hypothesis that the loading of bones by
      electrical stimulation-induced muscle contraction may prevent the mineral loss
      caused by gravitational unloading and bone growth will be maintained. During 10 d
      of hindlimb suspension, electrical stimulation at 1, 50, or 100 Hz was
      administered through the left sciatic nerve at the gluteal region of rats with
      approximately 300 g body weight. The dry weight, mineral content, and mineral
      density in hindlimb bones were analyzed. The dry weight and mineral content of
      femur and tibia-fibula in hindlimb-suspended rats tended to be less than in the
      age-matched cage controls. However, these detrimental effects were prevented by
      stimulation at 50 and 100 Hz. A positive effect of stimulation was seen even in
      the nonstimulated limb, although greater effect was induced in the stimulated
      limb. It is suggested that loading by stimulation-induced muscle contraction at
      higher frequencies is beneficial for the maintenance of bone growth or the
      prevention of mineral loss, or both, during hindlimb suspension in rats.

PMID- 9538288
TI  - Posthyperventilation hypoxemia after methacholine inhalation.
AB  - The hypothesis of this study was that hypoxemia after methacholine (MTH)
      inhalation is related not only to ventilation/perfusion inhomogeneity, but also
      to posthyperventilation hypoxemia. To test the hypothesis, we paid special
      attention to changes in gas exchange and ventilation parameters after MTH
      inhalation. Six stable asthma patients were investigated, and SaO2, minute
      ventilation (V.E), oxygen uptake rate in the lung (V.O2), carbon dioxide output
      rate in the lung (V.CO2), and respiratory exchange ratio (R) were measured. The
      SaO2 level decreased from a baseline level (before MTH inhalation) of 96.8 +/-
      1.0% (mean +/- SD) to the lowest level (the nadir SaO2) of 89.8 +/- 2.1% (p <
      0.01) in 200 +/- 50 s after MTH inhalation and gradually increased toward the
      baseline level. V.CO2 increased just after MTH inhalation (post-MTH) with
      increased V.E, and decreased at the nadir SaO2 with baseline V.E and PaCO2,
      indicating a decrease in breath-by-breath V.A and an increase in dead space
      minute ventilation at the nadir SaO2, but V.O2 remained close to constant. R
      increased post-MTH, decreased at the nadir SaO2, and thereafter increased
      gradually toward the baseline level with a time constant of 5.6 min. The addition
      of CO2 to inspired air partially suppressed hypoxemia. The consensus is that
      hypoxemia after MTH is solely attributable to the ventilation/perfusion
      inhomogeneity, but posthyperventilation hypoxemia is another reasonable
      interpretation of the hypoxemia after MTH with decreased V.A, V.CO2, and R. It is
      speculated that posthyperventilation normoventilation in respect to V.CO2 with
      baseline PaCO2 after MTH inhalation resulted in posthyperventilation hypoxemia as
      a result of relative hypoventilation in respect to V.O2.

PMID- 9538289
TI  - Cold stress facilitates calcium mobilization from bone in an ovariectomized rat
      model of osteoporosis.
AB  - In an ovariectomized rat model of osteoporosis, the effects of cold stress on
      intestinal Ca2+ transference and rate of bone turnover were evaluated. In the
      ovariectomized rats, a significant reduction in intestinal transference of Ca2+
      was associated with decreased activities of intestinal mucosal enzymes, alkaline
      phosphatase (AP), and calcium ATPase (Ca2+-ATPase) in all the different segments
      of small intestine in a descending gradient. The development of a high rate of
      bone turnover and osteoporosis in these animals was confirmed by significant
      alteration in plasma AP activity and calcium (Ca) level, urinary excretion of Ca
      and phosphate, and Ca : creatinine ratio. Cold stress in this model, apart from
      its unique influence in elevating plasma corticosterone and thyroid hormone
      level, enhanced all the above referred parameters studied in connection with
      intestinal transference of Ca2+, bone turnover rate, and osteoporosis. The
      results of this study emphasize that cold stress may have a positive influence on
      bone loss for an early development of hypogonadal osteoporosis in rats.

PMID- 9538290
TI  - Effect of hydration states on thermoregulatory responses during exercise in rats.
AB  - Thermoregulatory response during exercise was studied in rats with three
      hydration states: euhydration, hypohydration (-18% plasma volume by thermal
      dehydration), and hyperhydration (+24% plasma volume by 5% bovine serum albumin
      solution infusion). Rats exercised (12.5 m.min-1) for 30 min at an ambient
      temperature of 25 degrees C. Abdominal temperature (Tab) and heart rate were
      continuously recorded by using a surgically implanted transmitter and telemetry
      system, and the tail skin temperature (Tts) was measured as an index of
      peripheral vasomotor tone. In the euhydration group, Tts showed an increase when
      Tab reached 37.6 degrees C; an increase of Tts was observed at 37.9 degrees C of
      Tab in the hypohydration group and at 37.4 degrees C in the hyperhydration group.
      The slope of the Tts-Tab relationship was steeper in the hyperhydration group and
      less steep in the hypohydration group than in the euhydration group. These
      results indicate that hypohydration leads to an upward shift in the body
      temperature threshold for tail vasodilation and an increase in Tab during
      exercise. Hyperhydration, however, leads to a downward shift of the threshold and
      the maintenance of a lower Tab. An elevation of the threshold Tab for
      vasodilation was observed when plasma volume was reduced by more than 20%, and a
      decrease was observed when plasma volume increased more than 15%.

PMID- 9538291
TI  - Mechanisms of increased intracranial pressure in rabbits exposed to head-down
      tilt.
AB  - Changes in intracranial pressure (ICP) resulting from head-down tilt (HDT) were
      studied in rabbits, and a possible role of edema formation in the change of ICP
      was examined. Animals were anesthetized with pentobarbital sodium and
      artificially ventilated. ICP was continuously monitored through a catheter
      inserted into the subarachnoid space. It increased depending on the tilt angle
      and decreased when the tilt angle was reduced. ICP elevated from 4.6 +/- 0.7 mmHg
      (mean +/- standard error of the mean) at horizontal prone position to 13.7 +/-
      1.0 mmHg immediately after the onset of 45 degrees HDT and gradually reduced
      toward the pre-HDT baseline in the next 8 h. ICP decreased below the pre-HDT
      baseline value immediately after returning to the horizontal prone position, and
      gradually increased toward the baseline during the 2 h of recovery period.
      Histological examination (HE stain) demonstrated that exposure to 8 h of HDT did
      not cause remarkable edema in either the gray matter or the white matter in
      rabbits. Water content and specific gravity of brain tissues both were increased
      in the HDT group in comparison with the control group. These results suggest that
      edema formation plays little role in the elevation of ICP during the acute phase
      of HDT in rabbits.

PMID- 9538292
TI  - Inwardly rectifying K+ channel in retinal Muller cells: comparison with the KAB
      2/Kir4.1 channel expressed in HEK293T cells.
AB  - Inwardly rectifying K+ (Kir) channels are considered to play the major role in
      the spatial buffering of glial cells. We have examined the electrophysiological
      properties of Kir channels in isolated rabbit Muller cells (retinal glial cells).
      Although a previous study reported that three kinds of Kir channels with
      different conductance and rectification properties were expressed in distinct
      regions of rabbit Muller cell membrane, we could record only a single population
      of Kir channels from the distal end to the endfoot in 205 successful cell
      attached patches. The identified Muller cell Kir channel had a unitary
      conductance of 25 pS in the inward direction with symmetrical 153 mM K+
      condition. The conductance and gating properties of the Muller cell Kir channels
      were identical to those of the KAB-2/Kir4.1 heterologously expressed in a
      mammalian cultured cell line, HEK293T cells. Thus KAB-2/Kir4.1 was the
      predominant glial Kir channel not only in the brain, but also in the retina.
      Because its rectification is intermediate, this Kir channel may contribute to
      both the intrusion and the extrusion of K+ ions across glial cell membrane and
      may be the major pathway for redistribution of extracellular K+ ions in the
      central nervous system.

PMID- 9538293
TI  - Intracellular Mg2+ depletion depresses the delayed rectifier K+ current in guinea
      pig ventricular myocytes.
AB  - The effects of various [Mg2+]i, particularly low [Mg2+]i, on the delayed
      rectifier K+ current (IK) were studied in guinea pig ventricular myocytes with
      the patch clamp technique. The magnitude of IK was evaluated from the amplitude
      of its tail current elicited on repolarization following the depolarizing steps.
      The pipette-perfusion technique was also used. The initial variations of IK
      magnitude were dependent on [Mg2+]i in the internal solutions with which the
      whole-cell recording was begun. With 0.03 to 1 mM [Mg2+]i, IK was relatively
      stable after patch rupture, showing a minimal decay with time; with 3 mM [Mg2+]i,
      IK rapidly declined; with [Mg2+]i, less than 0.01 mM IK transiently increased
      after patch break, but declined progressively thereafter as the magnitude of IK
      decreased to about 30% of the initial magnitude in 10 min. The decline of IK at
      low [Mg2+]i showed the following features. The decline was accompanied little by
      changes in the voltage-activation relation or by changes in the kinetics of
      current deactivation. The decline was not related to changes in [Ca2+]i and was
      also observed in ATP gamma S-loaded, isoprenaline-stimulated cells, in which IK
      channels were presumed to be persistently phosphorylated. An application of
      okadaic acid did not prevent the decline of IK during Mg2+ depletion. It is
      suggested that a presence of [Mg2+]i higher than 0.01 mM is required to maintain
      IK in guinea pig ventricular cells. The depression of IK at low [Mg2+]i appears
      to involve a phosphorylation-dephosphorylation-independent mechanism.

PMID- 9538294
TI  - A comment on the analysis of bell-shaped dose-response curves.
AB  - A problem of the analysis of bell-shaped dose-response curves was theoretically
      discussed by using the response of ryanodine receptors for Ca2+ concentration as
      a model case. Usually the response curves were analyzed under the assumption that
      the receptor has a high affinity activation site and a low affinity inhibition
      site. However, a solution having a low affinity activation site and a high
      affinity inhibition site can be deduced theoretically from the same data. A
      method to avoid an erroneous result was proposed.

PMID- 9538295
TI  - Control of circadian variation in skin blood flow response to heat stress.
AB  - Six male subjects had their lower legs immersed in water at 42 degrees C for 60
      min at 4 different times of the day to study whether the skin blood flow response
      to passive heat stress shows circadian variation in the relationship between skin
      blood flow and local sweating rate. When skin blood flow was plotted against
      local sweating rate, three distinct phases were observed. Phase A, an increase in
      skin blood flow without sweating was maximal at night. But the slope of the
      regression line did not change over the day in Phase C. These findings suggest
      that there is circadian variation in the skin blood flow response before onset of
      sweating during passive heat stress. This variation might be related, in part, to
      the circadian rhythm in vasoconstrictor activity.

PMID- 9538296
TI  - Coronary artery remodelling.

PMID- 9538297
TI  - Ultrasonic imaging of aortic atheroma.

PMID- 9538298
TI  - Cholesterol embolisation.

PMID- 9538299
TI  - The electrocardiogram on stamps (Part 2).

PMID- 9538300
TI  - The clinical value of ambulatory blood pressure monitoring.

PMID- 9538301
TI  - Pulmonary thromboendarterectomy.
AB  - Although PTE is potentially curative for thromboembolic pulmonary hypertension,
      probably fewer than 1500 of these operations have been performed worldwide.
      Unquestionably, the disease is under-recognized, and even among cardiac surgeons
      PTE is considered very hazardous and perhaps of questionable long-term benefit.
      Our experience does not support this view. There is neither disagreement
      regarding the poor prognosis of patients with pulmonary hypertension nor the
      unsatisfactory results of medical treatment for this disease. The only surgical
      alternative to PTE is lung transplantation. Compared to lung transplantation, PTE
      offers a lower surgical mortality rate, better long-term survival, and fewer
      chronic complications. The mortality rate for PTE at our centre is now in the
      range of 5-7%, with documented sustained functional improvement in survivors.
      These results clearly favour PTE as the primary treatment for thromboembolic
      pulmonary hypertension, and physicians should be encouraged to identify patients
      with this now curable disease.

PMID- 9538302
TI  - Amiodarone and the thyroid: a practical guide to the management of thyroid
      dysfunction induced by amiodarone therapy.
AB  - Amiodarone induces predictable changes in thyroid function tests that are largely
      explicable in terms of the physiological effects of iodide excess and inhibition
      of deiodinase activity. Clinically relevant thyroid dysfunction is not uncommon
      during amiodarone therapy, and requires careful diagnosis and treatment. The
      diagnosis and management of thyrotoxicosis is probably best supervised by a
      specialist endocrinologist. Control of hypothyroidism can generally be achieved
      simply by the addition of T4 to the therapeutic regimen, ideally after an initial
      assessment by an endocrinologist. The frequency with which amiodarone causes
      thyroid and other complications serves to emphasize the need for rational
      prescribing and long-term cardiological follow up.

PMID- 9538303
TI  - Efficacy of a new balloon catheter for internal cardioversion of chronic atrial
      fibrillation without anaesthesia.
AB  - OBJECTIVE: To compare a new internal cardioversion system incorporated into a
      balloon guided catheter with a conventional two electrode system in patients with
      atrial fibrillation (AF). DESIGN: Prospective study. PATIENTS: 74 patients with
      chronic AF treated by internal cardioversion. MATERIALS: A 7.5 F balloon catheter
      with high energy electrode arrays each consisting of six 0.5 cm platinum rings.
      Brachial vein access enables one electrode array to be placed in the left
      pulmonary artery (distal pole) and the other at the lateral right atrial wall
      (proximal pole). The conventional two electrode system consists of 6 F electrodes
      placed in the proximal left pulmonary artery (anode) and the lower right atrium.
      INTERVENTIONS: Internal cardioversion was performed by shocks delivered in 40 V
      incremental steps from an external defibrillator. Shocks were applied by the new
      device to 32 patients (group A) and by the conventional system to 42 patients
      (group B). RESULTS: The groups differed with respect to system positioning (9.2
      (7.3) upsilon 12.3 (8.1) minutes, p < 0.05) and fluoroscopy times (1.7 (1.0) v
      3.3 (2.1) minutes, p < 0.01). Sinus rhythm was restored in 30 patients of group A
      and in 39 of group B (NS) with mean (SD) energy requirements of 8.4 (3.1) J and
      7.2 (3.1) J, respectively (NS). CONCLUSIONS: This new method of internal
      cardioversion has comparably high primary success rates and low sedation
      requirements with single and two lead systems.

PMID- 9538304
TI  - Investigation of the thoracic aorta in cholesterol embolism by transoesophageal
      echocardiography.
AB  - OBJECTIVES: To examine the thoracic aorta of patients with severe cholesterol
      embolism (CE) by transoesophageal echocardiography (TOE). METHODS: The thoracic
      aorta of 20 consecutive patients with CE was compared with that in a control
      population matched for age and risk factors by TOE. Patients were prescribed
      steroids after CE was diagnosed. Follow up is reported and compared with results
      in the literature. RESULTS: Aortic plaques and debris were more common in
      patients with CE than in the control population (p < 0.001 and p < 0.0001,
      respectively). The mean (SD) number of aortic plaques in the CE patients was 2.6
      (0.7). This aortic atheroma was found predominantly in the descending aorta. One
      patient died during a mean (SD) follow up of 24 (10) months. CONCLUSIONS: Aortic
      atheroma, as detected by TOE, should be considered as the main source of CE. In
      addition, the prognosis in our series, in which steroids were systemically
      prescribed, is much better than in others reported in the literature.

PMID- 9538305
TI  - Atherosclerotic coronary lesions with inadequate compensatory enlargement have
      smaller plaque and vessel volumes: observations with three dimensional
      intravascular ultrasound in vivo.
AB  - OBJECTIVE: To compare vessel, lumen, and plaque volumes in atherosclerotic
      coronary lesions with inadequate compensatory enlargement versus lesions with
      adequate compensatory enlargement. DESIGN: 35 angiographically significant
      coronary lesions were examined by intravascular ultrasound (IVUS) during
      motorised transducer pullback. Segments 20 mm in length were analysed using a
      validated automated three dimensional analysis system. IVUS was used to classify
      lesions as having inadequate (group I) or adequate (group II) compensatory
      enlargement. RESULTS: There was no significant difference in quantitative
      angiographic measurements and the IVUS minimum lumen cross sectional area between
      groups I (n = 15) and II (n = 20). In group I, the vessel cross sectional area
      was 13.3 (3.0) mm2 at the lesion site and 14.4 (3.6) mm2 at the distal reference
      (p < 0.01), whereas in group II it was 17.5 (5.6) mm2 at the lesion site and 14.0
      (6.0) mm2 at the distal reference (p < 0.001). Vessel and plaque cross sectional
      areas were significantly smaller in group I than in group II (13.3 (3.0) v 17.5
      (5.6) mm2, p < 0.01; and 10.9 (2.8) v 15.2 (4.9) mm2; p < 0.005). Similarly,
      vessel and plaque volume were smaller in group I (291.0 (61.0) v 353.7 (110.0)
      mm3, and 177.5 (48.4) v 228.0 (92.8) mm3, p < 0.05 for both). Lumen areas and
      volumes were similar. CONCLUSIONS: In lesions with inadequate compensatory
      enlargement, both vessel and plaque volume appear to be smaller than in lesions
      with adequate compensatory enlargement.

PMID- 9538306
TI  - Shrinkage of human coronary arteries is an important determinant of de novo
      atherosclerotic luminal stenosis: an in vivo intravascular ultrasound study.
AB  - OBJECTIVE: To assess the occurrence of arterial remodelling types and its
      relation with the severity of luminal stenosis in atherosclerotic coronary
      arteries. PATIENTS AND METHODS: Twenty one de novo coronary lesions of 20
      patients, who were scheduled for percutaneous transluminal coronary angioplasty
      (PTCA), were investigated with intravascular ultrasound before PTCA. Local
      arterial remodelling at the lesion site was studied by measuring the cross
      sectional area circumscribed by the external elastic lamina (EEL) relative to the
      reference site: (EEL area lesion/reference EEL area) x 100%. Three groups were
      defined. Group A: relative EEL area of less than 95% (shrinkage), group B:
      relative EEL area between 95% and 105% (no remodelling), group C: relative
      increase in EEL area of more than 105% (compensatory enlargement). RESULTS: All
      three types of remodelling were observed at the lesion site: group A (shrinkage)
      n = 8, group B (no remodelling) n = 5, group C (compensatory enlargement) n = 8.
      The mean (SD) relative EEL area at the lesion site in group A and C was 83(9)%
      and 132(30)%, respectively. In group A, 33% of the luminal area stenosis at the
      lesion site was caused by shrinkage of the artery. In contrast, group C showed
      that 87% of the plaque area did not contribute to luminal area stenosis because
      of compensatory arterial enlargement. CONCLUSIONS: These results show that both
      compensatory enlargement and paradoxical shrinkage occurs in the atherosclerotic
      coronary artery. Next to plaque accumulation, the type of atherosclerotic
      remodelling is an important determinant of luminal narrowing.

PMID- 9538307
TI  - Stenting of "unprotected" left main coronary artery stenoses: early and late
      results.
AB  - OBJECTIVE: To assess short and long term efficacy of coronary stent implantation
      for unprotected left main coronary artery stenosis. DESIGN: Retrospective follow
      up study. SETTING: Tertiary referral centre for interventional cardiology and
      cardiac surgery. PATIENTS: Eighteen consecutive patients (12 men; age 70.8 years)
      between May 1993 and July 1996. Ten patients presented with stable angina and
      underwent the procedure electively, eight patients presented either with unstable
      angina or myocardial infarction and underwent the procedure in emergency.
      INTERVENTION: Johnson and Johnson Palmaz-Schatz stents were used in 16 patients,
      and a Microstent and a Gianturco-Roubin in one patient each. An intra-aortic
      balloon pump was prophylactively used for two patients in the elective group. In
      the acute group, six required an intra-aortic balloon pump. MAIN OUTCOME
      MEASURES: Procedural success rate and major adverse cardiac events. RESULTS:
      Successful stent implantation was achieved in all patients. In the elective
      group, no major adverse cardiac event occurred during the procedure, but one
      patient had to undergo repeated angioplasty before discharge. All patients of the
      elective group were discharged alive and there has been one non-cardiac death
      during a follow up of (mean (SD)) 10 (4) months. In the emergency group, one
      patient died during the procedure, one patient developed a non Q-wave myocardial
      infarction, one patient underwent emergency coronary bypass surgery, while
      another patient died suddenly before hospital discharge. Six patients of the
      emergency group were discharged alive and there has been one non-cardiac death
      during a follow up of 7 (4) months. CONCLUSIONS: Elective stent implantation for
      unprotected left main coronary artery stenosis is safe and effective in selected
      stable patients. Urgent stent implantation, however, cannot be considered as a
      definitive procedure in emergency situation.

PMID- 9538309
TI  - High prevalence of arrhythmias in elderly male athletes with a lifelong history
      of regular strenuous exercise.
AB  - OBJECTIVE: To characterise cardiac arrhythmias and cardiac autonomic function in
      11 elderly men (mean (SD) age 73.2 (2.8) years) with a lifelong history of
      regular very strenuous, exercise. A control group of 12 healthy sedentary or
      moderately physically active men (74.5 (2.7) years) was also studied. DESIGN: 48
      hour ambulatory electrocardiograms were recorded. Cardiac autonomic function was
      estimated from power spectral analysis of heart rate variability. Maximal oxygen
      uptake during treadmill exercise testing was 2.91 (0.52) l (41 (7) ml/kg).
      RESULTS: Nine of 11 athletes had complex ventricular arrhythmias compared with
      five of 12 controls. Seven athletes but none of the controls had episodes of
      heart rate below 40 beats/min and two athletes had RR intervals longer than two
      seconds. Heart rate variability in the athletes was higher than in the controls.
      CONCLUSIONS: Elderly athletes with a lifelong training history seem to have more
      complex arrhythmias and profound bradyarrhythmias than do healthy elderly
      controls, which may increase the risk of sudden cardiac death. In contrast, the
      age related decrease in heart rate variability seems to be retarded, which has a
      positive prognostic value and may decrease the risk of life threatening
      ventricular arrhythmias.

PMID- 9538308
TI  - Lipophilic versus hydrophilic beta(1) blockers and the cardiac sympatho-vagal
      balance during stress and daily activity in patients after acute myocardial
      infarction.
AB  - OBJECTIVE: To compare the effects of a lipophilic and a hydrophilic beta(1)
      blocker on cardiac sympatho-vagal balance during daytime activity and stress in
      patients four to six weeks after myocardial infarction. DESIGN: Randomised,
      double blind, crossover study comparing the effect of atenolol (50 mg once daily)
      with metoprolol CR (100 mg once daily) with treatment periods of four weeks.
      SETTING: Large teaching hospital. PATIENTS: 50 patients (45 male, 5 female, age
      range 40 to 75 years), four to six weeks after an acute myocardial infarction.
      METHODS: At the end of each treatment period the 24 hour heart rate variability,
      heart rate variability power spectra during head up tilt and mental stress,
      baroreflex sensitivity, and exercise performance were evaluated. RESULTS: During
      daytime activity and during orthostatic and mental stress, both heart rate and
      the ratio between the low and high frequency spectral components of the heart
      rate variability were significantly lower with atenolol. Conversely, there was no
      difference between treatments in baroreflex sensitivity and resting plasma
      catecholamines. Exercise duration and peak oxygen consumption did not differ
      between treatments, but the heart rate during submaximal and peak exercise was
      significantly lower with atenolol. CONCLUSIONS: At the doses used in this study,
      atenolol achieved greater beta(1) adrenergic blockade than metoprolol CR and this
      was associated with significant inhibition of vagal withdrawal during stress.
      This suggests that peripheral blockade of beta(1) adrenergic receptors may be
      more important than central blockade in preventing stress induced vagal
      withdrawal in patients after myocardial infarction.

PMID- 9538310
TI  - Isoprenaline and inducibility of atrioventricular nodal re-entrant tachycardia.
AB  - OBJECTIVES: To examine the effect of isoprenaline on slow and fast pathway
      properties and tachycardia initiation. DESIGN: Consecutive patients, prospective
      study. SETTING: Referral centre for cardiology, academic hospital. PATIENTS: 24
      patients suffering from common type atrioventricular nodal reentrant tachycardia
      (AVNRT). INTERVENTIONS: Programmed electrical stimulation and radiofrequency
      catheter ablation of the slow pathway. MEASUREMENTS AND MAIN RESULTS: AVNRT was
      induced before and after the administration of isoprenaline in nine patients
      (group 1), before isoprenaline only in five (group 2), and after isoprenaline
      only in 10 (group 3). The anterograde effective refractory period of the fast
      pathway was prolonged significantly during isoprenaline administration in group 1
      (405 (31) v 335 (34) ms, p < 0.001) and shortened in group 2 (308 (57) v 324 (52)
      ms, p = 0.005). There was also significant shortening in group 3 (346 (85) v 395
      (76) ms, p < 0.001). Isoprenaline administration did not result in a significant
      change of the anterograde effective refractory period of the slow pathway in
      groups 1 and 3, but eliminated slow pathway conduction in group 2. Isoprenaline
      significantly shortened the minimal and maximal atrial to His bundle conduction
      interval recording in response to each extrastimulus of the slow pathway (210
      (24) v 267 (25) ms, p < 0.001 and 275 (25) v 328 (25) ms, p < 0.001,
      respectively) in group 1 and significantly prolonged these intervals (331 (34) v
      274 (34) ms and 407 (33) v 351 (33) ms, respectively) in group 3. In all groups
      only minimal changes in the refractory period of the atrium occurred after
      isoprenaline administration. The effect of isoprenaline was also measured on the
      ventricular effective refractory period and on the minimal and maximal length of
      the ventriculoatrial (V2-A2) interval during ventricular pacing. Isoprenaline did
      not result in a significant change of the ventricular effective refractory period
      in groups 1 and 2 nor of the shortest and longest V2-A2 interval. In group 3,
      however, the ventricular effective refractory period and the shortest and longest
      V2-A2 interval shortened significantly after isoprenaline administration.
      CONCLUSIONS: In group 1 isoprenaline did not affect inducibility of AVNRT because
      it prolonged the fast pathway refractory period without affecting slow pathway
      conduction. In group 2 isoprenaline shortened the fast pathway refractory period
      and appeared to abolish slow pathway conduction. Consequently, isoprenaline
      prevented induction of AVNRT. In group 3 isoprenaline facilitated induction of
      AVNRT. This effect seemed primarily to be the result of shortening of retrograde
      refractoriness of the fast pathway with prolongation of slow pathway anterograde
      conduction and refractory period.

PMID- 9538311
TI  - Nitric oxide, oxygen, and prostacyclin in children with pulmonary hypertension.
AB  - OBJECTIVE: To test the vasodilatory response of the pulmonary vascular bed in
      children with pulmonary hypertension. DESIGN: Prospective dose response study in
      which the effects of inhaled nitric oxide (NO) are compared with those of oxygen
      and intravenous prostacyclin. PATIENTS AND INTERVENTIONS: The vasodilator test
      was performed in 20 patients in whom mean pulmonary artery pressure (PAPm) was >
      or = 40 mm Hg and /or pulmonary vascular resistance index was > or = 4 Um2.
      Haemodynamic effects of inhaled NO (20, 40, and 80 ppm) at a fractional inspired
      oxygen (FiO2) value of 0.3, pure oxygen, oxygen at FiO2 0.9-1.0 combined with NO
      as above or with intravenous prostacyclin at 10 and 20 ng/kg/min were measured.
      RESULT: NO decreased PAPm with a dose response from 20 to 40 ppm (mean change at
      40 ppm-5.50, 95% confidence interval (CI) -7.98 to -3.02 mm Hg. Maximal decrease
      in the ratio of pulmonary to systemic vascular resistance was achieved with a
      combination of NO 80 ppm and oxygen (-0.18, 95% CI -0.26 to -0.10). Increase in
      the pulmonary flow index was greatest with pure oxygen in those with an
      intracardiac shunt (8.52, 95% CI -0.15 to 17.20 l/min/m2). Neither NO nor oxygen
      altered systemic arterial pressure but intravenous prostacyclin lowered systemic
      arterial pressure and resistance. CONCLUSIONS: NO selectively reduces pulmonary
      vascular resistance and pressure maximally at 40 ppm. Oxygen reduces pulmonary
      vascular resistance and NO potentiates this reduction without affecting the
      systemic circulation. Prostacyclin vasodilates the pulmonary and the systemic
      circulations.

PMID- 9538312
TI  - Treatment of pulmonary hypertension with the continuous infusion of a
      prostacyclin analogue, iloprost.
AB  - OBJECTIVE: To compare prostacyclin with an analogue, iloprost, in treatment of
      severe pulmonary hypertension. PATIENTS: Eight patients with severe pulmonary
      hypertension: primary in five, thromboembolic pulmonary hypertension in three.
      METHODS: All patients underwent right heart catheterisation. Mean (SEM) right
      atrial pressure was 9.9 (2.2) mm Hg, mean pulmonary artery pressure 67.4 (3.0) mm
      Hg, cardiac index 1.75 (0.13) l/min/m2 and mixed venous oxygen saturation
      59.1(3.1)%. Continuous intravenous epoprostenol (prostacyclin, PGI2) or iloprost
      was given for phase I (three to six weeks); the patients were then crossed over
      to receive the alternate drug in an equivalent phase II. MAIN OUTCOME MEASURES:
      Exercise tolerance was measured at baseline and at the end of phase I and II with
      a 12 minute walk; distance covered, rest period, percentage drop in arterial
      oxygen saturation (delta Sao2%) and percentage rise in heart rate (delta HR%).
      RESULTS: Walking distance covered rose from (mean (SEM)) 407.5 (73) to 591 (46) m
      with PGI2 (p = 0.004) and to 602.5 (60) m while on iloprost (p = 0.008). Rest
      period decreased from 192 (73) seconds at baseline to 16 (16) seconds with PGI2
      (p = 0.01) and to 58 (34) seconds with iloprost (p = 0.008). Delta HR% was
      37.5(6)% at baseline, 35(3)% on PGI2, and 24(6)% on iloprost (p = 0.04).
      CONCLUSIONS: Both intravenous PGI2 and iloprost caused significant improvement in
      exercise tolerance. Iloprost offers an alternative to PGI2 treatment of severe
      pulmonary hypertension.

PMID- 9538313
TI  - Monosomy 22q11 in patients with pulmonary atresia, ventricular septal defect, and
      major aortopulmonary collateral arteries.
AB  - OBJECTIVE: To describe the morphology of the pulmonary arteries in patients with
      pulmonary atresia, ventricular septal defect, and major aortopulmonary collateral
      arteries with and without monosomy 22q11. DESIGN: A retrospective analysis of all
      patients with this congenital heart defect who are being followed at the
      University Children's Hospital Erlangen. SETTING: A tertiary referral centre for
      paediatric cardiology and paediatric cardiac surgery. PATIENTS: 21 patients with
      pulmonary atresia, ventricular septal defect, and major aortopulmonary collateral
      arteries. Monosomy 22q11 was diagnosed by fluorescent in situ hybridisation using
      the D22S75 probe (Oncor). The morphology of the pulmonary arteries was assessed
      on the basis of selective angiograms. RESULTS: 10 patients (48%) were shown to
      have a microdeletion in 22q11 (group I). There was no difference with respect to
      the presence of confluent central pulmonary arteries between these patients (80%)
      and the remaining 11 patients (group II) without monosomy 22q11 (91%). Patients
      of group I, however, more often had arborisation anomalies of the pulmonary
      vascular bed (90% in group I v 27% in group II). Because of the more severe
      abnormalities of the pulmonary arteries, a biventricular repair had not been
      possible in any of the children with monosomy 22q11, though repair had been
      carried out in 64% of the children in group II. CONCLUSION: The developmental
      disturbance caused by the monosomy 22q11 seems to impair the connection of the
      peripheral pulmonary artery segments to the central pulmonary arteries in
      patients with pulmonary atresia, ventricular septal defect, and major
      aortopulmonary collateral arteries, resulting in a lower probability of
      biventricular repair.

PMID- 9538315
TI  - Myocardial infarction in young people with normal coronary arteries.
AB  - Myocardial infarction occurring in young people with angiographically normal
      coronary arteries is well described but the pathophysiology of this condition
      remains unknown. Coronary artery spasm in association with thrombus formation and
      minimal atheromatous disease or spontaneous coronary artery dissection are
      possible causes. Two young men presented with severe chest pain after acute
      alcohol intoxication and each sustained an extensive anterior myocardial
      infarction. Investigations including intravascular ultrasound showed no evidence
      of atherosclerotic coronary artery disease. Coronary artery spasm associated with
      acute alcohol intoxication as well as prothrombotic state and endothelial damage
      related to cigarette smoking may be mechanisms leading to acute myocardial
      infarction in these cases. Acute myocardial infarction occurs in young persons
      with normal coronary arteries and the diagnosis should be considered in young
      patients presenting with severe chest pain, particularly those abusing cocaine or
      alcohol, so that reperfusion therapy can be initiated promptly.

PMID- 9538314
TI  - Relation of genotype 22q11 deletion to phenotype of pulmonary vessels in
      tetralogy of Fallot and pulmonary atresia-ventricular septal defect.
AB  - OBJECTIVE: To compare the morphology of the pulmonary vessels in tetralogy of
      Fallot or pulmonary atresia-ventricular septal defect (PA-VSD) with (del22q) and
      without 22Q11 deletion (non-del22q). PATIENTS: 94 consecutive infants (54 with
      tetralogy of Fallot, 40 with PA-VSD) were studied using ultrasound and
      catheterisation. MOLECULAR INVESTIGATIONS: Identification of the 22q deletion was
      performed either by fluorescent in situ hybridisation or polymerisation chain
      reaction genotyping. RESULTS: 25 patients were del22q (16/40 (40%) PA-VSD v 9/54
      (17%) tetralogy of Fallot; p < 0.02). Major aortopulmonary collateral arteries
      was more common in patients with PA-VSD-del22q (p < 0.03). Such collaterals were
      identified in 13 patients: 10 del22q and three non-del22q (p < 0.001). The size
      of the right and left pulmonary arteries expressed as a standard deviation (SD)
      difference of the normal range was -4.2 (quartiles -5.3 and -2.9) for PA-VSD
      del22q, and -2.6 (-3.1 and -1.8) for PA-VSD non-del22q (p = 0.02). The mean (SD)
      difference between the measured and theoretical Nakata index was -373 (94) for PA
      VSD del22q v -245 (93) in PA-VSD non-del22q (p = 0.0002). In tetralogy of Fallot
      patients with and without del22q, the size of the pulmonary arteries was similar
      (p = 0.6). CONCLUSIONS: A "specific" phenotype could be defined in patients with
      deletion: PA-VSD, major aortopulmonary collateral arteries with complex loop
      morphology, and small central pulmonary arteries. Differences in the morphology
      of the pulmonary vessels may indicate a different timing of the faulty
      developmental pathway in patients with and without 22q11 deletion.

PMID- 9538316
TI  - Familial atrial fibrillation with fetal onset.
AB  - A woman presented during two pregnancies (at 25 and 23 weeks' gestation,
      respectively) because the fetuses had rapid, irregular tachycardia and hydrops.
      After maternal drug treatment and achievement of slower fetal heart rates, the
      hydrops gradually resolved. Both babies were born full term with continuing
      atrial fibrillation. In the first, an ectopic atrial rhythm was temporarily
      achieved during high dose flecainide treatment but, in the younger sibling, all
      medications and repeated cardioversions failed even temporarily to convert the
      atrial fibrillation with an almost isoelectric baseline in ECG to sinus rhythm.
      Good rate control has been achieved with digoxin in both patients. No infective,
      immunological, or structural cause was found in either case, and thus an
      inherited aetiology is probable.

PMID- 9538317
TI  - Left atrial thrombus as an early consequence of blunt chest trauma.
AB  - Thromboembolism is rarely considered in discussions of the complications of blunt
      chest trauma. The few cases of thromboembolism that have been reported in this
      setting have occurred in association with significant myocardial damage. A
      previously fit 23 year old woman was admitted to the intensive care unit
      following a road traffic accident. A day later, left atrial thrombus was
      demonstrated by transoesophageal echocardiography in the absence of any other
      evidence of important myocardial injury. Anticoagulation with heparin was
      cautiously introduced in spite of her extensive injuries, and there were no
      consequent bleeding complications. At hospital discharge on day 18 she was
      entirely well. Full anticoagulation with warfarin was continued for a further
      eight weeks at which time follow up transoesophageal echocardiography showed
      complete resolution of the thrombus.

PMID- 9538319
TI  - Rotational ablation assisted angioplasty of an obstructed aortopulmonary
      collateral artery.
AB  - A 15 month old baby girl with pulmonary atresia, ventricular septal defect, and
      multiple aortopulmonary collateral arteries underwent rotational ablation
      assisted balloon angioplasty of a severely stenosed collateral artery that had
      previously proved undilatable using a high pressure non-compliant balloon
      angioplasty catheter. It is postulated that the rotablation debulked a fibrotic
      stricture within the artery to facilitate effective balloon dilatation.
      Rotational ablation assisted angioplasty may have a role to play in congenital
      stenotic lesions that are "undilatable".

PMID- 9538318
TI  - Traumatic damage to the mitral valve during percutaneous balloon valvotomy for
      critical aortic stenosis.
AB  - Percutaneous balloon valvuloplasty is now a widely accepted alternative to
      surgical valvotomy for patients with congenital aortic valve stenosis. Mitral
      valve anomalies are well known to coexist and influence the prognosis from all
      palliative procedures. Two cases of mitral valve injury occurring during balloon
      aortic valvuloplasty are reported, one an 11 month old boy, the other a 2 day old
      baby boy. Both cases were characterised by an unusually posterior position of the
      guidewire, over which the balloon was deployed. The wire, and hence the balloon,
      may have been placed through the tension apparatus of the mitral valve with
      subsequent damage to its free edge on inflation. This is at least conceptually
      more likely to occur if the orifice of the valve is posterior, if there is a
      small left ventricular cavity, or if the mitral valve itself is abnormal-features
      present in both cases. Possible strategies for decreasing the incidence of such
      damage are considered.

PMID- 9538320
TI  - A young mother with severe chest pain.

PMID- 9538321
TI  - Dietary precautions and listeria endocarditis?

PMID- 9538322
TI  - Histological findings in non-hypertrophic cardiomyopathy associated with Noonan's
      syndrome.

PMID- 9538323
TI  - Antibiotic treatment of streptococcal, enterococcal, and staphylococcal
      endocarditis. Working Party of the British Society for Antimicrobial
      Chemotherapy.

PMID- 9538324
TI  - Expression of parathyroid hormone-related protein (PTHrP) and the PTH/PTHrP
      receptor in the rat uterus during early pregnancy and following artificial
      deciduoma induction.
AB  - The interaction between parathyroid hormone-related protein (PTHrP) and the
      parathyroid hormone (PTH)/PTHrP receptor is thought to play a role in the growth
      and differentiation of various tissues throughout fetal development in the
      rodent. The aim of the present study was to define the patterns of expression of
      PTHrP and of the PTH/PTHrP receptor in the rat uterus during the early stages of
      normal pregnancy, and following artificial induction of a decidual reaction.
      Using hybridization histochemistry, we have shown that the receptor gene is
      switched on early in pregnancy (by 1.5 days post coitum) in the endometrial
      stromal cells that surround the lumen. These cells include the anti-mesometrial
      subepithelial stromal cells that are destined to become decidualized. This
      pattern continues until 5.0 days post coitum, when PTHrP is switched on in
      antimesometrial luminal epithelial cells that line the implantation chamber.
      Stromal cells underlying the implantation chamber then downregulate transcription
      of the receptor gene, and within 12 h differentiate into decidual cells. A
      similar pattern was seen in uteri in which a decidual reaction had been induced
      artificially. Therefore, it may be postulated that in early pregnancy the
      endometrial stroma initiates transcription of the gene for the PTH/PTHrP receptor
      and is thus 'primed' for the PTHrP signal from the luminal epithelial cells. Some
      time after receiving the signal, the endometrial stromal cells downregulate the
      receptor gene, and this appears to be a trigger for the terminal differentiation
      of the stromal cells into decidual cells. These results suggest that PTHrP,
      acting through the PTH/PTHrP receptor, plays a role in the initiation of a
      decidual reaction during early pregnancy by regulating the differentiation of
      endometrial stromal cells into decidual cells.

PMID- 9538325
TI  - Production of normal offspring from mouse oocytes injected with spermatozoa
      cryopreserved with or without cryoprotection.
AB  - Epididymal mouse spermatozoa were suspended in various physiological solutions
      (CZB, PBS or isotonic saline) with or without 18% (w/v) raffinose before cooling
      to -20 degrees, -50 degrees or -196 degrees C and storage for 1-28 days. After
      thawing, a few spermatozoa frozen with raffinose were partially motile (about 2%)
      but in all other treatments they were immotile and diagnosed as 'dead' by
      staining that differentiates between live and dead spermatozoa. Almost all
      oocytes injected with sperm heads (nuclei) from spermatozoa frozen with and
      without raffinose were fertilized normally (95-100%) and developed to the two
      cell stage (89-100%). No differences were found between the physiological media.
      The majority of oocytes fertilized with spermatozoa frozen in CZB medium
      developed to blastocysts (80-94%) but development was significantly reduced after
      fertilization with spermatozoa frozen in PBS and isotonic saline especially in
      the absence of raffinose (69 and 70% versus 51 and 50%). Normal fertile offspring
      were obtained in all treatments but there were significantly fewer offspring with
      spermatozoa stored at -196 degrees C in isotonic saline with or without raffinose
      and CZB with raffinose. Testicular spermatozoa were extremely sensitive to
      cryodamage: about 50% frozen to -196 degrees C in CZB with or without raffinose
      disintegrated after thawing. Almost 100% of oocytes injected with sperm heads
      from intact (at light microscope level) testicular spermatozoa developed to the
      two-cell stage but development to blastocysts was reduced significantly compared
      with that of controls especially those without raffinose. The data indicate that
      cryopreservation of sperm nuclei requires less stringent conditions than those
      for the retention of normal physiological function of intact spermatozoa.
      Motility and plasma membrane integrity are not essential for fertilization and
      the production of live offspring when nuclei of nonviable spermatozoa are
      injected into oocytes.

PMID- 9538326
TI  - Ultrasound image attributes of bovine ovarian follicles and endocrine and
      functional correlates.
AB  - Heifers were studied to determine whether computer-assisted quantitative
      echotexture analysis of ultrasound images reflect functional and endocrine
      characteristics of dominant and subordinate follicles at specific stages of
      development. Heifers were examined using transrectal ultrasonography each day
      until ovariectomy on day 3 (n = 8) and day 6 (n = 9) of wave 1, day 1 of wave 2
      (n = 7), or after onset of pro-oestrus > or = days after ovulation (n = 8) to
      obtain growing, early-static, late-static and regressing dominant follicles of
      wave 1, subordinate follicles, preselection follicles and preovulatory dominant
      follicles. Ultrasound images of the follicles were obtained in vitro and analysed
      using custom-developed computer algorithms. Mean pixel (picture element) values
      (grey-scale: black = 0, white = 255) for the follicle wall and stroma increased
      (P < 0.05) progressively from the growing to the regressing phases of the
      dominant follicle of wave 1. The antrum and wall of subordinate follicles had
      higher (P < 0.05) mean pixel values than that of the corresponding dominant
      follicles. Pixel heterogeneity (a measure of variation of grey-scale values of
      pixels) of images of the follicle antrum and wall increased (P < 0.05)
      progressively during the early-static to regressing phases. A progressive
      increase (P < 0.05) in the slope of the regression line of pixel values for the
      follicle wall was detected from the growing to the regressing phases of the
      dominant follicle of wave 1. The regression line of the wall of the preovulatory
      dominant follicle had the lowest (P < 0.05) slope. Oestradiol concentration in
      the follicular fluid decreased (P < 0.05) from the growing to the late-static
      phase, while a marked decrease (P < 0.05) in the androstenedione concentration
      was recorded between the growing and the early-static phases of the dominant
      follicle. Progesterone content did not increase until follicles were in the final
      stages of regression. Pixel heterogeneity of the antrum and wall, and the slope
      of the follicle wall regression line were negatively correlated (P < 0.001) with
      oestradiol and the oestradiol:progesterone ratio in follicular fluid. The results
      of this study support the hypothesis that echotexture characteristics of
      ultrasound images of the follicle antrum and wall are correlated with the
      functional and endocrine status of a follicle.

PMID- 9538327
TI  - Effect of restricted nutrition on timing of puberty in female Soay sheep.
AB  - Ovariectomized, oestradiol-implanted Soay ewe lambs from 21 September (aged 21
      weeks) had restricted (liveweight maintenance) (n = 4) or unrestricted food (n =
      4); ovary-intact lambs had unrestricted food (n = 8). LH activation in
      ovariectomized lambs on restricted and unrestricted food and onset of ovulatory
      cycles in ovary-intact lambs all occurred on 7 December (SED 8.8 days) (32
      weeks), but at different liveweights (24.2, 17.9 and 18.3 kg, respectively, SED
      1.22). LH pulse frequency was similar in ovariectomized lambs on restricted and
      unrestricted food. From 29 August (aged 18 weeks), Soay ewe lambs in seasonally
      advanced decreased artificial daylength were given restricted food, unrestricted
      food, or food was restricted for 8 weeks and then unrestricted (n = 8 per group).
      Ovarian cycles started 3 weeks earlier than in lambs in natural photoperiod on
      similar dates for all three groups (14, 18 and 19 November, respectively, SED 5.5
      days) (29 weeks), but at different liveweights (16.2, 20.7, and 18.4 kg,
      respectively, SED 0.87). From 1 August, Suffolk x Greyface ewe lambs (aged 16
      weeks) had restricted food, unrestricted food, or food restricted for 8 weeks and
      then unrestricted (n = 8 per group). By 1 November (29 weeks), 0/8 lambs on
      restricted food (29.3 +/- 0.92 kg) but 8/8 lambs on unrestricted food an 5/8
      lambs on 8 weeks of restricted food had ovulated (mean dates: 16 October +/- 2.5
      days (27 weeks, 40.1 +/- 1.02 kg), and 1 November +/- 3.0 days (29 weeks, 35.5 +/
      1.23 kg), respectively. Thus, nutritional growth restriction during the 11 weeks
      preceding normal puberty delayed pubertal data in the improved breed but did not
      influence the timing of puberty in the unimproved Soay breed within the weight
      range studied.

PMID- 9538328
TI  - Viability of small preantral ovarian follicles from domestic cats after
      cryoprotectant exposure and cryopreservation.
AB  - About 1500 preantral follicles can be recovered from a single cat ovary by
      mechanical dissection. This is a potentially rich source of genetic material if
      ova could be preserved and grown in vitro, especially from rare or endangered
      species that die abruptly or are ovariectomized for medical reasons. The aims of
      this study were to examine cryoprotectant toxicity and then the potential of
      successfully cryopreserving preantral cat follicles. In the initial toxicity
      trial, isolated cat follicles (40-90 micron) were exposed to dimethylsulfoxide,
      glycerol, 1,2-propandiol or ethylene glycol at 0 degrees C for 15 min. Follicle
      viability was assessed by supravital staining using a combination of Trypan blue
      and Hoechst 33258 at O h, and after 18 h and 1 week of culture. Percentages of
      follicles with intact oocytes and granulosa cells were similar (P > 0.05) among
      control (no cryoprotectant), dimethylsulfoxide, 1,2-propandiol and ethylene
      glycol treatments at all time points, but were reduced (P < 0.05) after glycerol
      exposure. On the basis of this finding, dimethylsulfoxide and 1,2-propandiol were
      used to cryopreserve intact follicles, and post-thaw viability was assessed by
      supravital staining and 5-bromo-2'-deoxyuridine uptake into oocytes and granulosa
      cells during culture. Of control (noncryopreserved) follicles, 31.4% +/- 2.9%,
      18.8% +/- 1.9% and 16.2% +/- 1.6% were intact after O h, 18 h and 1 week of
      culture, respectively. Uptake of 5-bromo-2'-deoxyuridine occurred in
      approximately 20% of follicles at all time points. On the basis of the presence
      of both a healthy oocyte and granulosa cells, cryopreservation in
      dimethylsulfoxide or 1,2-propandiol allowed approximately 19% of follicles to
      survive. Approximately 10% demonstrated clear evidence of cell activity that was
      sustainable for 1 week. In conclusion, the cat ovary contains a population of
      preantral follicles that are not adversely affected by short-term exposure to
      most conventional cryoprotectants. Furthermore, there is a subpopulation of these
      follicles capable of surviving cryopreservation, remaining structurally intact
      and physiologically active after thawing.

PMID- 9538329
TI  - Expression of epidermal growth factor and its receptor in equine placental
      tissues.
AB  - Northern blot and in situ hybridization techniques have demonstrated a marked
      increase in mRNA encoding epidermal growth factor (EGF) in the endometrium of
      mares, coincident with the start of interdigitation between the allantochorion
      and endometrium during placentation. In the present study, the unusually high EGF
      expression in the epithelium of the endometrial glands was shown to be maintained
      until at least day 250 of gestation (term = 320-340 days) in mares carrying
      normal horse conceptuses. However, in mares carrying failing donkey-in-horse
      pregnancies created by embryo transfer, EGF expression was severely retarded in
      those areas of the endometrium that were heavily infiltrated with lymphocytes and
      which showed a failure of placental development. Specific receptors for EGF were
      also detected in tissue homogenates from pregnant mares using 125I-labelled human
      EGF. Binding was high in the fetal membranes (allantochorion), both before
      implantation (days 30-34) and in the fully developed placenta (days 150-250), and
      was equivalent to the level of binding to homogenates of adult liver and kidney.
      Binding was much reduced in endometrial homogenates before implantation and from
      non-pregnant mares but increased after implantation to reach values equivalent to
      those exhibited by the fetal membranes. Scatchard analysis of displacement curves
      indicated a single class of high-affinity binding sites in the fetal membranes
      and pregnant endometrium sampled at day 150 of pregnancy and chemical cross
      linking of the receptor-125I-labelled EGF complexes in fetal membranes revealed
      two radiolabelled bands of 170 kDa and 150 kDa. A large excess of insulin-like
      growth factor I (IGF-I) failed to displace any labelled EGF from the tissue
      homogenates. The marked and sustained upregulation of endometrial EGF expression
      during pregnancy in mares, and the presence of EGF receptors in the fetal
      allantochorion and maternal endometrium, suggest a possible role for EGF in the
      marked growth of these two tissues during placentation in equids.

PMID- 9538330
TI  - Effect of antagonism of the parathyroid hormone (PTH)/PTH-related protein
      receptor on decidualization in rat uterus.
AB  - Parathyroid hormone-related protein (PTHrP) was detected at 32.8 +/- 3.9 pmol 1-1
      in uterine luminal fluid from immature rats treated with oestradiol. As mRNA
      encoding PTHrP has previously been localized to implantation sites in pregnant
      rats, the role of luminal PTHrP during pregnancy was explored. Infusion of a
      parathyroid hormone (PTH)/PTHrP receptor antagonist, [Asn10,Leu11]PTHrP(7-34)
      amide, into the uterine lumen during pregnancy in rats resulted in excessive
      decidualization. This effect was also observed after intrauterine infusion of a
      monoclonal antibody raised against PTHrP. The effect of infusion of PTH/PTHrP
      receptor antagonist was dependent upon successful implantation, was dose
      dependent and confined to the treated horn. A decrease in the number of apoptotic
      decidual cells in antagonist-infused uterine horns compared with vehicle or non
      infused horns was detected immunohistochemically at day 13 of pregnancy, and this
      decrease is likely to contribute to the 'over-decidualization' observed. In
      pseudopregnant rats, infusion of PTH/PTHrP receptor antagonist into the uterine
      lumen resulted in an increase in uterine wet weight of the infused horn compared
      with the non-infused horn, indicating a direct effect on deciduoma formation.
      Thus, activation of the PTH/PTHrP receptor by locally produced PTHrP appears to
      be crucial for normal decidualization during pregnancy in rats.

PMID- 9538331
TI  - Effects of dose of LH on androgen production and luteinization of ovine theca
      cells cultured in a serum-free system.
AB  - The study reports the development of a serum-free culture system for sheep thecal
      cells that overcomes the problem of spontaneous luteinization and the use of this
      system to study the control of proliferation and differentiation. Theca cells
      were isolated by enzymatic dispersion from small follicles (< 3.5 mm) and the
      effect of plating densities (25-100 x 10(3) cells per well), LH (0.001-100
      micrograms l-1), insulin (1-5000 micrograms l-1), insulin-like growth factor I
      (IGF-I) analogue (1-100 micrograms LR3-IGF-I l-1) and epidermal growth factor
      (EGF) (0.005-50 micrograms l-1) on the number of cells and androstenedione and
      progesterone production were determined. Plating density had a marked effect on
      the pattern of hormone secretion with densities between 50 and 75 x 10(3) cells
      per well resulting in a high androstenedione: progesterone ratio at optimum doses
      of LH (0.1 micrograms l-1: P < 0.001). In the first 48 h, the production of both
      androstenedione and progesterone was stimulated in a dose-dependent manner by LH
      (P < 0.001). However, the production of androstenedione was ten times higher than
      that of progesterone and was more sensitive to LH (ED50 value 0.08 micrograms l-1
      for androstenedione and 1 microgram l-1 for progesterone). From 48-144 h of
      culture higher doses of LH (> 1 ng ml-1) inhibited androstenedione (P < 0.001)
      and stimulated progesterone (P < 0.001) and resulted in a marked change in cell
      morphology, thus reflecting both functional and morphological luteinization. At
      optimum doses of LH, both insulin and IGF stimulated cell proliferation (P <
      0.001) and androstenedione production (P < 0.001) in a dose responsive manner and
      there was a significant (P < 0.001) interaction between them. In contrast, both
      insulin and IGF-I inhibited (P < 0.001) progesterone production in a dose
      responsive manner. EGF stimulated cell proliferation (P < 0.001) and progesterone
      production (P < 0.001), but inhibited androstenedione production (P < 0.001), in
      a dose responsive manner. In conclusion, this culture system exhibits
      physiologically relevant responses to known in vivo modulators of follicle
      development. The biphasic nature of the theca cell response to LH emphasises the
      exquisite sensitivity of theca cells to LH stimulation and highlights the
      importance of dose-response relationships in the gonadotrophic control of ovarian
      function.

PMID- 9538332
TI  - Ontogeny of the opioidergic regulation of LH and prolactin secretion in lactating
      sow. I: failure of naloxone to antagonize suckling-induced changes in LH and
      prolactin secretion in early lactation, irrespective of pattern of
      administration.
AB  - The principal aim of this study was to investigate the ontogeny of an opioidergic
      mechanism mediating the suckling-induced inhibition of LH secretion during
      lactation in sows. In contrast to an increase in LH secretion in response to
      naloxone treatment on days 10 and 11 of lactation (P < 0.05), a single injection
      of 2 mg naloxone kg-1 at 39, 51, 63, or 75 h post partum had no effect. However,
      the last of four injections of 2 mg naloxone kg-1 given at 12 h intervals to
      group IV sows did elicit a positive LH response (P < 0.05). Multiple injections
      of 1 mg naloxone kg-1 at 3 h intervals over 30 h on day 10-11 consistently
      increased (P < 0.05) mean plasma LH with no evidence of induced refractoriness to
      repeated use of the antagonist. Similarly, naloxone did not affect mean plasma
      prolactin in the immediate postpartum period, but either repeated naloxone
      treatments on day 10-11 or single naloxone injections on day 10 or 11 of
      lactation decreased plasma prolactin (P < 0.05). Therefore, the regulation of LH
      and prolactin secretion in lactating sows changes with time post partum. An
      opioid-dependent mechanism is an important component of the suckling-dependent
      regulation of LH and prolactin secretion in established lactation, but not during
      the first 72 h postpartum period.

PMID- 9538334
TI  - Deterioration of goat spermatozoa in skimmed milk-based extenders as a result of
      oleic acid released by the bulbourethral lipase BUSgp60.
AB  - The aim of the present study was to elucidate the mode of action of goat
      bulbourethral lipase (BUSgp60 lipase) previously identified as responsible for
      the deterioration of goat sperm viability in skimmed milk-based extenders. Milk
      fractions were purified by micro- and ultrafiltration and characterized by SDS
      PAGE, thin layer chromatography, triglyceride quantitative analysis and by their
      ability to potentiate the lipase and the sperm-deteriorating activity of the
      bulbourethral lipase. Components in both the phosphocaseinate and soluble whey
      protein fractions enhanced the lipase activity of BUSgp60 but only the
      phosphocaseinate fraction, which contains triglycerides, promoted deterioration
      of spermatozoa in the presence of bulbourethral gland secretion. These data
      suggest that the sperm-deteriorating effect of bulbourethral gland secretion is
      due to the catalysis of triglyceride hydrolysis, and that proteins increase this
      activity. BUSgp60 hydrolysed milk triglycerides and triolein very effectively,
      and its lipase activity was enhanced by several highly purified milk proteins.
      The major cis-unsaturated fatty acid from milk (oleic acid) but not the major
      saturated fatty acid (palmitic acid) exhibited dose-dependent detrimental effects
      on goat spermatozoa. Therefore, the catalysis of oleic acid formation from
      residual milk triglycerides by BUSgp60 appears responsible for the deterioration
      of goat spermatozoa when unwashed semen is diluted in skimmed milk-based
      extenders. The precise mechanism of action of oleic acid remains to be elucidated
      but the drawbacks of washing buck semen might be avoided by inhibiting BUSgp60 or
      by depriving it of substrate.

PMID- 9538333
TI  - Reduction in fluid secretion by rat testis by drugs that block potassium
      channels.
AB  - The effect of two class III antiarrhythmic drugs (Almokalant, Astra-Hassle and
      Dofetilide, Pfizer) on fluid secretion by rat testes has been examined. Both
      drugs reduced fluid secretion, whether this was measured by the amount of rete
      testis fluid that could be collected 22 h after unilateral efferent duct
      ligation, or by the difference in mass between the ligated and unligated testes,
      or by the difference in amount of supernatant fluid after the parenchyma of the
      ligated and unligated testes had been dispersed and centrifuged. The secretion of
      potassium, calculated from the amount of potassium in the supernatant fluids from
      the ligated and unligated testes was also reduced by the drugs, whereas the
      secretion of androgen-binding protein and inositol was unaffected. The
      concentration of potassium in the secreted fluid, calculated from the amount and
      composition of the supernatant fluids, was not affected by treatment of the rats
      with Almokalant, but was increased in rats treated with Dofetilide and, in these,
      the concentration of sodium was reduced and that of magnesium and inositol was
      increased and the concentration of total protein was unaffected. The
      concentration of androgen-binding protein in secreted fluid was increased in rats
      treated with Almokalant, while the concentration of testosterone was unaffected.
      Histological examination of testes from treated rats revealed phagocytosis of
      stage 19 spermatids in tubules at stages VIII-IX after 2 days, at stages IX-XI
      after 4 days and at stages VIII-XIV after 7 days, apparently owing to an effect
      on spermiation. It appears that these drugs interfere with potassium-mediated
      fluid secretion by the testis, leading to the other changes seen.

PMID- 9538335
TI  - Effect of pituitary adenylate cyclase-activating polypeptide (PACAP) on progestin
      biosynthesis in cultured granulosa cells from rat ovary and expression of mRNA
      encoding PACAP type IA receptor.
AB  - The purpose of this study was to detect the presence of mRNA encoding pituitary
      adenylate cyclase-activating polypeptide (PACAP) type I receptor in granulosa
      cells from rat ovary and to examine the effect of PACAP on progestin
      biosynthesis. mRNA was isolated from granulosa cells from the ovaries of immature
      rats treated with pregnant mares' serum gonadotrophin. The technique of reverse
      transcription and polymerase chain reaction with primers specific to PACAP type I
      receptor were used to demonstrate the expression of mRNA encoding PACAP type IA
      receptor in these cells. Granulosa cells were also cultured in the absence or
      presence of 100 ng LH ml-1 with various doses of PACAP-38 (10, 100 and 1000 ng ml
      1). At the end of the incubation period, the incubation media were collected and
      concentrations of progesterone, 20 alpha-hydroxypregn-4-en-3-one (20 alpha-OH-P)
      and cAMP were measured. Increasing concentrations of PACAP-38 significantly
      stimulated the production of progestins (progesterone and 20 alpha-OH-P) and cAMP
      accumulation in a dose-dependent manner (P < 0.01; ANOVA). This effect was
      observed in media cultured for 24 and 48 h in both basal and LH-stimulated
      states. PACAP-38 did not significantly affect the ratio of progesterone: 20 alpha
      OH-P produced by granulosa cells cultured for 24 h in the LH-stimulated state.
      However, at 1000 ng ml-1, PACAP-38 significantly decreased the ratio of
      progesterone to 20 alpha-OH-P production in granulosa cells cultured for 48 h (P
      < 0.01). These results suggest that granulosa cells from rat ovary express mRNA
      encoding PACAP type IA receptor and that PACAP may regulate granulosa cell
      differentiation and play an important role in the reproductive process.

PMID- 9538336
TI  - hCG-stimulated ovarian carbonyl reductase in relation to preovulatory ovarian
      follicular growth.
AB  - The relationship between carbonyl reductase, which is localized in the theca and
      interstitial cells, and ovarian follicular development was evaluated by measuring
      the enzyme activity and concentration of carbonyl reductase, and examining its
      immunohistochemical localization in immature rats treated with equine chorionic
      gonadotrophin (eCG), ovine(o) FSH and hCG. eCG and oFSH were administered s.c. to
      26-day-old rats, and the ovaries were isolated 48 and 72 h after treatment. hCG
      was administered s.c. 48 h (at 28 days of age) after eCG or oFSH, and the ovaries
      were isolated 6 or 9 h after treatment. Both eCG and oFSH significantly increased
      the ovarian carbonyl reductase concentration 48 h after treatment compared with
      the saline-treated group, but the increase with eCG was approximately twice that
      with oFSH. Seventy-two hours after treatment, eCG further increased both carbonyl
      reductase activity and its concentration. Ovulation was also induced. oFSH
      stimulated only ovarian follicular growth without further increase in either
      activity or concentration. In addition, eCG increased the immunoreactivity to
      anti-carbonyl reductase antibody in the theca and interstitial cells, but oFSH
      did not. Treatment with hCG in saline-pretreated rats increased carbonyl
      reductase activity by 2.8-fold and carbonyl reductase concentration by 4.1-fold
      after 9 h compared with the 0 h concentration, without producing the large
      follicles observed with eCG and oFSH. However, the stimulatory effect of hCG on
      ovarian carbonyl reductase in eCG- or oFSH-pretreated rats was weaker than that
      in saline-pretreated rats. These results suggest that ovarian carbonyl reductase
      is induced by LH/hCG but not by FSH and that the enzyme induced by hCG is
      unrelated to preovulatory ovarian follicular growth.

PMID- 9538337
TI  - The effects of epidermal growth factor and insulin-like growth factor I on the
      metabolic activity, nuclear maturation and subsequent development of cattle
      oocytes in vitro.
AB  - The effects of epidermal growth factor (EGF) and insulin-like growth factor I
      (IGF-I) on the maturation and subsequent development of cattle oocytes in vitro
      were evaluated in three experiments. Cumulus-oocyte complexes (COC) were
      collected from cattle ovaries and matured for 20-24 in control medium or in
      medium containing 50 ng EGF ml-1, 100 ng IGF-I ml-1, EGF + IGF-I, or 10% (v/V)
      fetal calf serum plus 0.1 i.u. human menopausal gonadotrophin ml-1 (hMG). In Expt
      1, treatment with EGF + IGF-I stimulated cumulus expansion, the metabolism of
      pyruvate and glutamine, and nuclear maturation. In Expt 2, only the metabolic
      measurements from oocytes that reached metaphase II were considered, and EGF +
      IGF-I stimulated pyruvate metabolism to the same extent as serum + hMG. In Expt
      3, the oocytes were fertilized after maturation culture, and the resultant
      embryos cultured for up to 8 days. The cleavage was greater in the EGF and EGF +
      IGF-I groups than in the controls but less than in the serum + hMG group.
      Moreover, the number of blastocyst cells at 7 days after insemination and the
      proportion of cleaved embryos that developed to the blastocyst stage by day 8 was
      greater in the serum + hMG group than in the control group indicating that
      maturation treatment can affect early embryonic development. In conclusion, EGF +
      IGF-I can stimulate cumulus expansion, oxidative metabolism, nuclear maturation
      and cleavage after fertilization of bovine oocytes in vitro. The relative effects
      of the treatments on oocyte pyruvate metabolism in Expts 1 and 2 generally
      paralleled their effects on cleavage and subsequent development in Expt 3,
      suggesting that mitochondrial function is related to developmental potential.
      Further investigation is required to determine which component(s) of serum or
      gonadotrophin treatment is responsible for the effects on subsequent embryonic
      development.

PMID- 9538338
TI  - In vitro association of six oviductal fluid proteins with the bovine zona
      pellucida.
AB  - Oviductal fluid proteins have been shown to associate with gametes in several
      species. The objective of the present study was to identify bovine oviductal
      fluid proteins that associate with the bovine zona pellucida. Oviductal fluid was
      obtained daily from two dairy cows with normal oestrous cycles via indwelling
      oviductal cannulae. Fluid was collected from the ampullary and isthmic regions of
      the same oviduct. Oviductal fluid samples were pooled by oviduct region and
      according to stage of the oestrous cycle as determined by the concentration of
      serum progesterone. Samples collected when serum progesterone concentrations were
      > 1.5 ng ml-1 were combined into luteal pools. Non-luteal pools consisted of
      oviductal fluid samples collected on days when serum progesterone concentrations
      were < or = 1.5 ng ml-1. Each oviductal fluid sample was assayed fpr protein
      concentration, and an aliquot equivalent to 10 mg ml-1 was biotinylated using
      biotinamidocaproate N-hydroxysuccinimide ester at a concentration of 1 mg ml-1.
      Cumulus-free, non-viable bovine oocytes were incubated in the biotinylated
      oviductal fluid samples for 3.5 h. Oocytes were washed, the zonae mechanically
      ruptured, solubilized, and subjected to one-dimensional SDS-PAGE. Separated
      proteins were transferred to nitrocellulose and probed with avidin-horseradish
      peroxidase. Five biotinylated oviductal fluid proteins were found to associate
      with the zona pellucida in all treatments. These proteins had apparent molecular
      masses of 80, 74, 60, 45, and 30 kDa. An additional protein, of molecular mass 95
      kDa, was found associated with zonae from oocytes incubated in non-luteal fluid
      of both regions, but not from oocytes incubated in luteal fluid. This protein was
      shown to be bovine oestrus-associated protein by using a monospecific polyclonal
      antibody.

PMID- 9538339
TI  - Acute and specific impairment of spermatogonial development by GnRH antagonist
      induced gonadotrophin withdrawal in the adult macaque (Macaca fascicularis).
AB  - This study examined the effect of GnRH-antagonist (GnRH-A)-induced gonadotrophin
      withdrawal on numbers of germ cells in adult cynomolgus monkeys and aimed to
      identify the site of the earliest spermatogenic lesion(s) produced. Animals
      received either GnRH-A (Cetrorelix; 450 micrograms kg-1 day-1 s.c.; n = 5) or
      vehicle (control, n = 4) for 25 days. One testis was removed on day 16 and the
      other testis on day 25. The optical disector stereological method was used to
      estimate germ and Sertoli cell numbers per testis. After GnRH-A treatment for 16
      days, the number of type A spermatogonia was unchanged; however, type B
      spermatogonia (15% of control), preleptotene + leptotene + zygotene (15% control)
      and pachytene (55% control) spermatocytes were all reduced (P < 0.05). By day 25,
      these cells were further reduced together with step 1-6 spermatids (38% control;
      P < 0.05). More mature germ cells were unaffected. The proportion of type A pale
      spermatogonia at stages VII-XII was reduced (P < 0.05) in GnRH-A-treated groups
      (52% on day 16, 43% on day 25) compared with control (67%). After 25 days of GnRH
      A treatment, the number of Sertoli cells was unaltered but nuclear volume was
      reduced (66% control, P < 0.05). Tubule length was unchanged but volume (50%
      control), diameter (62% control) and epithelial thickness (59% control) were
      reduced (P < 0.05). GnRH-A treatment suppressed serum testosterone concentrations
      into the castrate range, and testicular testosterone concentrations to 21-36% of
      control values. Serum inhibin (as an index of FSH action) was suppressed in GnRH
      A-treated animals by day 16, declining to 38% of control concentrations at day
      25. Therefore, the primary lesion produced by GnRH-A induced gonadotrophin
      withdrawal is the rapid and profound reduction in the number of type B
      spermatogonia. The time course of germ cell loss suggests the inhibition of type
      A pale spermatogonial mitosis as the primary mechanism. Later germ cell
      maturation, specifically meiosis and spermiogenesis, appears to proceed
      unaffected. The decline in late spermatocytes and spermatids by 25 days of GnRH-A
      treatment is attributed to a 'depletional wave' from the spermatogonial lesion.
      The fact that such marked spermatogenic disruption occurs in the face of
      substantial testicular testosterone concentrations implies a significant role for
      FSH in spermatogonial development.

PMID- 9538340
TI  - Characterization of conceptus-produced goat interferon tau and analysis of its
      temporal and cellular distribution during early pregnancy.
AB  - Two proteins (17 and 22-24 kDa) produced by day 17 goat conceptuses were purified
      from in vitro culture media. Analysis of their N-terminal amino acid sequences
      and of their antiviral activity confirmed that both proteins belonged to the
      interferon tau family characteristic of ruminant conceptuses. The two molecules
      were glycosylated (22-24 kDa) or nonglycosylated (17 kDa) isoforms of the same
      protein. The time course of secretion was plotted and immunoblotting of the
      protein contents of uterine flushings from day 13 to day 21 of pregnancy was
      performed. The nonglycosylated isoform (17 kDa) was first detected on day 16;
      both isoforms were present at day 17 and, thereafter during pregnancy, the two
      proteins were not present in uterine flushings. Immunohistochemistry was used to
      show that the goat interferon tau was present in the trophoblastic cells as early
      as day 14 and until day 17. However, immunostaining was not uniform along the
      conceptus; labelling was greater at the abembryonic pole than at the embryonic
      pole. By day 18, as implantation proceeded, goat interferon tau was no longer
      detected. These results confirmed that the goat conceptus secretes interferon tau
      during the period of maternal recognition of pregnancy but its rapid decrease
      suggests that other factors need to be present by day 18 to take over its role in
      the maintenance of luteal function.

PMID- 9538341
TI  - Primary modulation by oestradiol of the production of an oviduct-specific
      glycoprotein by the epithelial cells in the oviduct of newborn golden hamsters.
AB  - The effects of steroid hormones (oestradiol and progesterone) on the appearance
      of a golden hamster oviduct-specific glycoprotein (GHOGP) in the epithelium of
      the oviduct of the newborn golden hamster were investigated by immunoblotting and
      immunohistochemical staining with a GHOGP-specific monoclonal antibody. Newborn
      golden hamsters (1.5 days old) were injected daily with oestradiol (1 microgram)
      or progesterone (10 microgram). An oviductal extract of oestradiol-treated golden
      hamsters for 4 days apparently immunoreacted with the monoclonal antibody on a
      broad band with a molecular mass of more than 200 kDa by immunoblotting under
      reducing conditions. This broad band was consistent with the migration of GHOGP
      in an extract of adult oviducts. Consecutive daily injections of oestradiol
      induced the appearance of GHOGP in undifferentiated epithelial cells of the
      oviduct of neonates. In oviducts of oestradiol-injected animals, GHOGP was first
      detected in the Golgi region and then increased in amount to fill the
      supranuclear cytoplasm of the epithelial cells. The inductive effect of
      oestradiol was dose-dependent. In contrast, consecutive daily injections of
      progesterone had no effect on the appearance of GHOGP in the oviductal
      epithelium. The effects of oestradiol and progesterone in organ culture of
      oviducts were examined in vitro, by culturing oviductal organs from 1.5-day-old
      newborn golden hamsters in chemically defined medium supplemented with oestradiol
      or progesterone for 2 days and then subjected to immunohistochemical staining.
      The immunoreaction was detected only in the epithelial cells of oestradiol
      treated oviducts at concentrations of > 0.01 ng ml-1, but not in the cells of
      untreated and progesterone-treated oviducts. These results indicate that the
      production of GHOGP in the epithelial cells of the oviduct of newborn golden
      hamsters is induced by oestradiol both in vivo and in vitro. It is suggested that
      oestradiol may be involved in the synthesis of GHOGP in the oviduct during
      postnatal development of golden hamsters.

PMID- 9538342
TI  - The 'hybrid' character of the gametes and reproductive tracts of the African
      shrew, Myosorex varius, supports its classification in the Crocidosoricinae.
AB  - The Soricidae are generally considered to comprise two subfamilies--Crocidurinae
      and Soricinae--each of which has distinctive reproductive characteristics.
      Although Myosorex varius is classified as a crocidurine, the features of its
      reproductive system call that classification into question. Compared with three
      other shrew genera, Myosorex exhibited a number of specific features including a
      relatively prolonged time (about 22 h) for ovulation to be induced by hCG
      injection and the smallest diameter (75 microns) recorded for any mammal egg.
      Moreover, the relative testis mass and the number of epididymal spermatozoa were
      somewhat greater than in some other shrews studied recently. However, many
      reproductive features in Myosorex have a 'hybrid' character. The glans penis has
      spines similar to those evident in crocidurines but absent in soricines, yet the
      accessory sperm storage site, midway along the vas deferens, is similar to that
      in soricine shrews. The ultrastructure of Myosorex spermatozoa was primarily
      soricine, despite an unduly large acrosome, which reaches its apogee in the
      Crocidurinae. Whereas the Fallopian tube displays a crocidurine-type isthmus
      characterized by deep crypts throughout, the ampulla is richly endowed with
      ciliated crypts, which in soricines contain spermatozoa. The first polar body
      persists in the Myosorex ovum, as it does in the soricines Cryptotis and Blarina,
      but not in the crocidurine Suncus and Crocidura. However, the cumulus oophorus of
      Myosorex appears largely crocidurine by virtue of its persistent intercellular
      junctions, long term stability, and the absence of a matrix, lacking only the
      unique perizonal space that finally characterizes the cumulus of the
      crocidurines, Suncus and Crocidura. The 'hybrid' character of the reproductive
      system of Myosorex is more consistent with the proposal that the genus is a
      survivor of a primitive subfamily--the Crocidosoricinae--from which present day
      Soricinae and Crocidurinae have arisen.

PMID- 9538343
TI  - Influence of insulin on follicular development and the intrafollicular insulin
      like growth factor I (IGF-I) system in sows after weaning.
AB  - Twenty-four crossbred primiparous sows were used to investigate the influence of
      insulin administration after weaning on the intrafollicular insulin-like growth
      factor i (IGF-I) system. Sows received 0.4 i.u. insulin kg-1 bodyweight or an
      equivalent volume of saline for 3 days (n = 5 insulin; n = 4 saline) or 5 days (n
      = 5 insulin; n = 6 saline) after weaning or served as untreated controls on day 1
      (n = 4). The number and diameters of ovarian follicles were recorded, and fluid
      was aspirated from the 20 largest follicles for determination of oestradiol and
      IGF-I by radioimmunoassay and of insulin-like growth factor-binding proteins
      (IGFBPs) by western ligand blotting. The walls of the follicles were collected
      for mRNA analysis by RNase protection assay or granulosa cells were collected for
      estimation of apoptosis by flow cytometry. Insulin treatment resulted in smaller
      diameters of all follicles (P < 0.05) and tended (P < 0.07) to increase the
      number of follicles available on day 5 compared with saline-treated animals (19.8
      versus 17.8). The concentration of oestradiol in follicular fluid from large (7
      10 mm) follicles on days 3 and 5 was reduced (treatment by size class
      interaction; P < 0.05) by insulin treatment. Insulin also reduced intrafollicular
      concentrations of IGF-I at days 3 and 5 after weaning (treatment by day
      interaction; P < 0.02) while the amounts of IGFBP-3 and IGFBPs of molecular mass
      30 and 22 kDa decreased from day 3 to day 5 in saline-treated animals only
      (treatment by day interaction; P < 0.05). Gene expression for IGF-I increased in
      saline-treated animals but decreased fourfold in insulin-treated sows from day 3
      to day 5 (treatment by day interaction; P < 0.002). Gene expression for IGFBP-d
      decreased (P < 0.04) from day 3 to day 5, while expression of IGFBP-2 was
      unaffected by treatment or day. Overall, insulin influenced the IGF-I system in a
      manner consistent with slowing follicular growth and possibly allowed more
      follicles to become available for ovulation.

PMID- 9538344
TI  - The cytoskeleton of human myometrial cells.
AB  - Eukaryotic cells have an internal cytoskeletal scaffolding, giving them their
      distinctive shapes. The cytoskeleton enables cells to transport vesicles, undergo
      changes in shape, migrate and contract. This dynamic structure is formed by three
      classes of filamentous assembly: actin microfilaments, intermediate filaments and
      microtubules. In this investigation the cytoskeleton of cultured human myometrial
      cells was studied by immunohistochemistry using specific antibodies against
      vinculin, cytokeratin, vimentin, tubulin and RhoA, covalently labelled with a
      fluorescent tag. Polymerized actin was visualized with fluorescein-conjugated
      phalloidin. Myometrial cells were very rich in actin fibres, which generally
      appeared as parallel bundles along the longest axis of the cells. There was a
      strong expression of vinculin which concentrated at actin--vinculin focal
      adhesion sites. By contrast, intermediate filaments (vimentin and cytokeratin)
      were organized in a dense cytoplasmic meshwork which excluded the nuclear space.
      A similar pattern was observed for tubulin. RhoA had a diffuse distribution and
      was associated with actin fibres. Exposure of the cells to oxytocin provoked a
      10% shortening of actin stress fibres. These results demonstrate that myometrial
      smooth muscle cells have a rich cytoskeletal structure and that agonists that
      stimulate myometrial activation provoke measurable changes in actin fibres which
      may be important for efficient contractility.

PMID- 9538345
TI  - Aging and occupational and environmental medicine.

PMID- 9538346
TI  - Aging healthcare professionals.

PMID- 9538347
TI  - Why and how to control for age in occupational epidemiology.
AB  - In occupational epidemiology, the need to consider the age factor properly
      influences the choice of study design and analytical techniques. In most studies,
      age is viewed as a potential confounder. Age is strongly associated with end
      points of interest in occupational epidemiology (diseases, physiological
      characteristics, doses of xenobiotics, etc), but to measure age as a confounder
      it must be associated with the exposure under study. When the exposure of
      interest is time related-for example, duration of employment, time since first
      exposure, cumulative exposure-a strong intrinsic association with age can be
      anticipated, and age will behave as a (usually strong) confounder. When
      occupational exposures without a direct relation with age-for example, job,
      department, type of exposure-are evaluated, the degree and direction of
      confounding bias cannot be anticipated. Control of the confounding effect of age
      can be accomplished in the design phase of a study by way of randomisation,
      restriction, and matching. Randomisation is seldom viable in occupational
      settings. Restriction is rarely used in the case of age. Matching is often used
      in a case-control study as a method to increase the study efficiency, but it must
      be followed by proper matched or stratified analysis. Options for age adjustment
      in the analysis phase involve stratification and regression methods. In
      longitudinal studies the modified life table analysis is used to take into
      account the fact that subjects cross categories of age as the study proceeds.
      Stability of relative measures of effect over age strata favoured the greater use
      of relative risks than risk differences. In the presence of effect modification
      the influence of age should not be eliminated; its interaction with exposure
      should be explicitly considered.

PMID- 9538348
TI  - Aging and work: the occupational health services' perspective.

PMID- 9538349
TI  - Air pollution and life expectancy: is there a relation?

PMID- 9538350
TI  - Injuries after falls at work in the United Kingdom and Sweden with special
      reference to fractures in women over 45.
AB  - OBJECTIVES: To describe the relation with age of risk of reported injury after a
      fall among women at work in two countries, the United Kingdom and Sweden, with
      particular emphasis on fractures, and to interpret these data. METHODS: Rates of
      accidents compiled under the national reporting regulations of each country
      during a two year period were described by age, sex, cause (fall on the level,
      fall from a height, other), and occurrence of fracture, with emphasis on the
      relative risk (RR) in workers aged 45 years and over compared with those aged
      under 45. For fractures (major fractures only in the United Kingdom) among women,
      RRs were calculated for all occupations, with the three digit occupational
      classification schemes of each country. Summary RRs for older versus younger
      women, directly standardised for occupation, were derived. RESULTS: Among women,
      RRs for injury after a fall on the level and fall from a height were 2.77 and
      1.77 respectively in Sweden and 2.28 and 1.54 in the United Kingdom. When
      restricted to fractures, the RRs became 4.75 and 3.66 respectively in Sweden and
      3.35 and 1.97 in the United Kingdom. Standardisation for occupation gave RRs for
      fractures of 4.87 and 3.75 in Sweden and 3.43 and 2.16 in the United Kingdom.
      Almost all occupational groups with enough fractures for analysis showed an
      excess of fractures related to falls among older women. A different age pattern
      was seen for all injuries or fracture after other types of accidents and for all
      types of accident in men. CONCLUSION: It is argued that, for fractures at least,
      the results for women are unlikely to be due to reporting bias and unlikely to be
      explained by a greater exposure to workplace hazards among older women. Whether
      there is an increased risk of falling, as distinct from sustaining a fracture, is
      not clear. The generality of the increased risk suggest that efforts should be
      made to minimise hazards in all occupational sectors, particularly those using
      many women.

PMID- 9538351
TI  - Repeated survey on changes in musculoskeletal complaints relative to age and work
      demands.
AB  - OBJECTIVES: To examine changes in musculoskeletal complaints over four years in
      groups of employees relative to age and work demands. METHODS: Repeated
      questionnaire data of male employees in heavy physical work (exposed group, n =
      7324) and mental work (control group, n = 4686), stratified for age (20-9, 30-9,
      40-9, 50-9), were analysed. For each employee, data on the occurrence of
      musculoskeletal complaints from two surveys with a mean interval of around four
      years were available. Changes in prevalences over the follow up interval were
      analysed. Proportions of new, recovered, and chronic cases as well as those free
      of complaints at both surveys were studied. RESULTS: For most complaints, there
      were significantly greater increases in prevalences in the exposed group compared
      with the control group over the follow up interval particularly within the group
      aged 40-9 for back, neck, and several sites of the upper and lower limbs. The 20
      9 year age group also had significantly greater changes for several
      musculoskeletal complaints. Within the oldest age group (50-9) exposure to heavy
      physical work demands only affected changes in prevalences of neck and upper arm
      complaints. After four years in the cohort free of complaints at the start of the
      follow up the group aged 40-9 had the highest prevalence of complaints of the
      back, neck, and the upper and lower limbs. CONCLUSIONS: Middle aged and younger
      employees develop musculoskeletal complaints as a result of exposure to heavy
      physical work. In the oldest age group health related selection seems to mask the
      occupational health risks under study. To prevent the expected increase in
      musculoskeletal disorders and related work disability in our aging workforce,
      preventive measures should be taken at all stages of a working life.

PMID- 9538352
TI  - Selection related to musculoskeletal complaints among employees.
AB  - OBJECTIVES: To (a) describe differences in the outcome of cross sectional and
      longitudinal analysis on musculoskeletal complaints relative to age and work
      demands, and (b) to assess the entrance and drop out selection on musculoskeletal
      complaints among groups of employees relative to age and work demands. METHODS: A
      study population was selected on the basis of questionnaire data from periodical
      occupational health surveys of almost 45,000 employees collected between 1982 and
      1993. From all companies within this data base that participated twice in company
      wide surveys four years apart, male employees were selected, and stratified for
      age and work demands. There were several populations: follow up (participation in
      both surveys); drop out (participation only in the first survey); entrance
      (participation only at the second survey); and two cross sectional populations
      (all participants at each survey). Prevalences of back complaints and turnover
      rates were analysed. RESULTS: Reported back complaints in the cross sectional
      analysis declined over the oldest age groups in heavy physical work versus a
      small increase in the longitudinal analysis. The age group 50-9 and back
      complaints were identified as predictors at the first survey for not
      participating at the second survey. Neither age nor work demands at the first
      survey indicated drop out among those employees with back complaints at the first
      survey. The effects of entrance selection on estimated prevalences were small.
      CONCLUSIONS: The results indicate that musculoskeletal disorders lead to
      selection out of work, affecting the validity of both cross sectional and
      longitudinal epidemiological studies. In future studies analyses of turnover
      figures on musculoskeletal complaints relative to work demands and age are
      recommended.

PMID- 9538353
TI  - Reanalysis of the occurrence of back pain among construction workers: modelling
      for the interdependent effects of heavy physical work, earlier back accidents,
      and aging.
AB  - OBJECTIVES: To re-examine the relation between heavy physical work and the
      occurrence of sciatic pain among construction workers reported previously to be
      absent in an epidemiological study. METHODS-Poisson log linear regression was
      used to model for the frequency of sciatic pain among concrete reinforcement
      workers and maintenance house painters with adjustment for the interactive
      effects of earlier back accidents and aging that modified the relation. RESULTS:
      Concrete reinforcement work not only had a direct effect on the frequency of
      sciatic pain, but it also contributed significantly to the risk indirectly
      through earlier back accidents. The risk of sciatic pain increased from age 25 to
      54 in a different manner for a worker depending on his occupational group and
      record of back accidents. CONCLUSIONS: Epidemiological studies on low back pain
      need to be analysed with sound methodology. This is important in view of future
      meta-analyses that will be performed for the purpose of providing guidelines on
      the prevention of back disorders in heavy physical work.

PMID- 9538354
TI  - Aging, rhythms of physical performance, and adjustment to changes in the sleep
      activity cycle.
AB  - OBJECTIVES: Shiftwork causes disturbances of the normal sleep-wake cycle and
      circadian rhythm. There is concern that aging workers have more problems than
      younger counterparts when the human body clock is disrupted. This review
      considers issues relating to aging, the circadian body clock, and adjustment to
      altered sleep-wake schedules. METHODS: Reports on effects of aging on the human
      body clock were reviewed. Research concerned with adjustment to circadian phase
      shifts (as occurs in night work) was considered. RESULTS: With aging there is an
      increased tendency towards morningness which is linked with difficulties in
      sleeping. The peak time and amplitude of normal circadian rhythms are altered.
      Tolerance of shiftwork can be linked with social factors as well as adaptation of
      the body clock. CONCLUSIONS: People habituated to night work seem to have
      developed mechanisms which allow them to cope with disruptions to lifestyle and
      the endogenous body clock. Elderly people are more suited to phase advances, as
      occur in morning workshifts, than to phase delays such as nocturnal work.

PMID- 9538355
TI  - Occupational exposure to carcinogens and risk of lung cancer: results from The
      Netherlands cohort study.
AB  - OBJECTIVES: To investigate risk of lung cancers associated with common
      established carcinogenic occupational exposures (asbestos, paint dust, polycyclic
      aromatic hydrocarbons, and welding fumes) in a prospective cohort study among the
      general population, and to estimate the proportion of lung cancer cases
      attributable to these occupational exposures. METHODS: A prospective cohort study
      on diet, other lifestyle factors, job history, and cancer risk that started in
      1986 in The Netherlands on 58,279 men, aged 55-69 years. Based on information
      about job history obtained from a self-administered questionnaire, case by case
      expert assessment was carried out to assign to each study subject a cumulative
      probability of occupational exposure for each carcinogenic exposure. For
      analysis, a case-cohort approach was used, in which the person-years at risk were
      estimated from a randomly selected subcohort (n = 1688). After 4.3 years of
      follow up, 524 lung cancer cases with complete job history were available.
      RESULTS: After adjustment for age, each of the other occupational exposures, and
      for smoking habits and intake of vitamin C, beta-carotene, and retinol,
      significant associations were found between risk of lung cancer and cumulative
      probability of occupational exposure to asbestos (relative risk (RR) highest/no
      exposure = 3.49, 95% confidence interval (95% CI) 1.69 to 7.18, trend P < 0.01 or
      paint dust (RR highest/no exposure = 2.48, 95% CI 0.88 to 6.97, trend P < 0.01).
      The population attributable risks (PARs) for the four exposures based on the
      multivariately adjusted RRs for ever exposed versus never exposed workers were
      calculated. The PAR of lifetime occupational exposure to asbestos was calculated
      to be 11.6%. CONCLUSIONS: This prospective cohort study among the general
      population showed that occupational exposure to asbestos or paint dust is
      associated with higher RRs for lung cancer. This study shows that after
      adjustment for smoking and diet about 11.6% of the cases of lung cancer in men is
      attributable to lifetime occupational exposure to asbestos.

PMID- 9538356
TI  - Deaths and tumours among workers grinding stainless steel: a follow up.
AB  - OBJECTIVE: To study cause specific mortality and cancer morbidity in workers
      exposed to the dust of grinding materials, grinding agents, and stainless steel,
      especially with regard to a possibly increased risk of respiratory, stomach, and
      colorectal cancer. METHODS: Retrospective cohort study, using reference cohorts
      of blue collar workers and population rates for comparison. The exposed cohort
      comprises workers with at least 12 months employment time at two plants,
      producing stainless steel sinks and saucepans (n = 727). Also, reference cohorts
      of other industrial workers (n = 3965) and fishermen (n = 8092) were analysed.
      The observation period began 15 years after the start of employment. Standardised
      mortality or incidence ratios (SMRs, SIRs; county reference rates) were
      calculated for cause-specific mortality between 1952 and 1993, and for cancer
      morbidity between 1958 and 1992. RESULTS: In the exposed cohort, overall
      mortality, cardiovascular mortality, and all malignant mortality and morbidity
      were slightly lower than expected. Also, the risk estimates for cancer in the
      upper and lower respiratory tracts and for stomach cancer were lower than
      expected. There was an increase in morbidity from colon cancer, which was
      explained by an excess of tumours in the sigmoid part only. Here, the risk
      estimates were higher in workers with long employment time (1-14 years: four
      observed cases, SIR 1.7, 95% confidence interval (95% CI) 0.4 to 4.5; > or = 15
      years: three observed cases, SIR 4.3, 95% CI 0.9 to 13) and the increased risk
      was especially pronounced among those first employed before 1942. A slight
      nominal excess of rectal cancers (nine observed cases, SIR 1.4, 95% CI 0.6 to
      2.6), and a significant excess of prostate cancer morbidity (36 observed cases,
      SIR 1.7, 95% CI 1.2 to 2.4) were found. These risk estimates did not, however,
      increase with employment time. CONCLUSIONS: The finding of an increased risk of
      cancer in the sigmoid part of the colon, which was not found in the reference
      cohorts, and with indication of a relation between duration of employment and
      response, is consistent with a causal relation. The limited size of the exposed
      cohort makes a detailed exposure-response analysis unstable, and the confidence
      limits are wide. Albeit slightly raised, the risk estimate for rectal cancer in
      the exposed cohort was not different from the estimate among the other industrial
      workers.

PMID- 9538357
TI  - Respiratory allergy in laboratory animal workers: a retrospective cohort study
      using pre-employment screening data.
AB  - OBJECTIVES: To study the role of exposure, atopy, and smoking in the development
      of laboratory animal allergy (LAA) in a retrospective cohort study. METHODS:
      Between 1977 and 1993, 225 people received a pre-employment screening when they
      started a job at a Dutch research institute where they were going to work with
      laboratory animals. After active follow up 136 of them (60.4%) could be traced
      and were sent a questionnaire with extensive questions on allergic symptoms,
      smoking habits, and job history. 122 people (89.7%) sent back a completed
      questionnaire. Those who were accepted for a job at the institute and did not
      have allergic symptoms at the start of the job were selected as cohort members.
      After selecting people with complete data on start and end date of jobs, exposure
      intensity, atopy, and smoking, the cohort consisted of 99 people with an average
      time of follow up of 9.7 years. LAA was defined as a positive response to a set
      of questions in the questionnaire. The mean number of hours a week a person was
      exposed to laboratory animals at entry of the cohort was used as a surrogate for
      exposure, and was divided into four categories. RESULTS: 19 cohort members
      (19.2%) reported LAA. More people with asthmatic symptoms were found in the high
      exposure categories. More atopic than non-atopic people reported asthmatic
      symptoms (13% v 6%). The mean time until development of symptoms of LAA was about
      109 months in non-atopic people (n = 9), and 45 months in atopic people (n = 10)
      (t test; P < 0.05). Time until development of symptoms of LAA was shorter at a
      higher intensity of exposure, except for those exposed for less than two hours a
      week. A proportional hazard regression analysis showed that exposure and atopy
      were significant determinants of LAA. An increased relative risk (RR) was found
      for non-atopic people exposed to laboratory animal allergens for more than two
      hours a week. Atopic people had an even higher risk when exposed to laboratory
      animals for more than two hours a week (RR above 7.3). Sex, smoking, and age were
      not risk factors. More atopic than non-atopic people were absent from work or
      transferred because of allergies. CONCLUSIONS: This study showed that exposure
      and atopy are significant predictors of LAA and that the risk of developing LAA
      remained present for a much longer period (> 3 y) than considered before.

PMID- 9538358
TI  - Bronchial reactions to exposure to welding fumes.
AB  - OBJECTIVES: To study the airway response and its mechanism to welding fumes in
      six welders with respiratory symptoms. METHODS: Methacholine and welding
      challenge tests were carried out. The concentration of welding fumes during the
      exposure test was measured. On two subjects who developed bronchoconstricition to
      welding challenge, additional tests were carried out including prick, patch, and
      inhalation challenges with metal salt solutions. RESULTS: Three subjects
      developed immediate bronchial reaction to exposure to welding fume; one to mild
      steel and stainless steel welding, another to mild steel and galvanised welding,
      and one only to galvanised welding. They all had a moderate to pronounced degree
      of non-specific bronchial hyperresponsiveness. The concentration of fumes during
      welding tests, particularly to galvanised welding, was high. An inhalation
      challenge test with zinc chloride salt solution in two subjects who reacted to
      galvanised welding was negative. Prick and patch tests with zinc chloride were
      also negative. CONCLUSION: The airway response to welding in these subjects is
      non-specific and is due to irritation rather than to sensitisation.

PMID- 9538359
TI  - Urinary arsenic concentration in a high arsenic area of south west England.

PMID- 9538360
TI  - [Coronary angiography: 1st or 2nd-line test?].
AB  - Coronary angiography, although now performed extremely frequently, remains an
      invasive and expensive examination, whose place, as first-line diagnostic method,
      must be discussed; Its main advantage is to provide a definitive diagnosis of
      coronary atherosclerosis as well as simple prognostic indicators (single vessel,
      two-vessel or three-vessel disease; concomitant evaluation of left ventricular
      function by associated radiological ventriculography). However, it is unable to
      precisely assess the degree of coronary wall disease and, more importantly,
      cannot evaluate the functional repercussions of stenosis. Under these conditions,
      only cases in which myocardial revascularization is expected to provide a
      definite clinical benefit (presence of frank angina symptoms) probably justify
      first-line coronary angiography. In all other cases, coronary angiography is a
      useful examination to provide reference "mapping" of the coronary lesions, but an
      obvious clinical benefit for the patient cannot be expected from systematic use
      of this technique. In particular, in such situations, coronary angiography should
      not be the only element on which the decision to perform myocardial
      revascularization should be based: the "oculostenotic reflex" must always be
      avoided.

PMID- 9538361
TI  - [Effect of stimulation on ventricular kinetics: contribution to the treatment of
      cardiomyopathies].
AB  - Cardiac pacing using the apex of the right ventricle as site of excitation
      induces asynchronous contraction between the right ventricle and the left
      ventricle as well as inversion of the normal left ventricular activation
      sequence. These two phenomena are responsible for alteration of septal kinetics
      and overall contractility. It has recently been demonstrated that these
      alterations can be used to advantage to reduce the degree of subaortic
      obstruction of patients suffering from hypertrophic and obstructive
      cardiomyopathy, and to improve their exercise tolerance. Using an opposite
      approach, consisting of reducing the degree of asynchronous contraction related
      to the presence of intraventricular conduction disorders, while optimizing
      atrioventricular synchronism, new pacing methods have recently been able to
      improve cardiac output and functional tolerance of some patients suffering from
      dilated cardiomyopathy. Although cardiac pacing can now be considered to be an
      alternative a surgery for the treatment of refractory forms of hypertrophic and
      obstructive cardiomyopathy, it still constitutes a research technique in the
      field of dilated cardiomyopathy.

PMID- 9538362
TI  - [Aspirin in secondary cardiovascular prevention: from clinical studies to daily
      practice].
AB  - The clinical benefit of aspirin in coronary insufficiency has been validated in
      the acute phase of myocardial infarction and in secondary prevention with a
      reduction of the risk of recurrent infarction of the order of 30%. By interfering
      with the process of thrombolysis, aspirin modifies the natural history of
      coronary artery disease by decreasing the frequency and severity of pathological
      events. Although a relative consensus has been reached concerning the dosages
      (160 to 325 mg/day), the use of aspirin nevertheless remains very insufficient,
      sometimes because of the risk of gastrointestinal intolerance related to the
      gastrotoxicity of aspirin, hence the importance of pharmaceutical forms designed
      to improve the gastrointestinal tolerance, such as calcium carbasalate (soluble
      aspirin complex), which appears to be particularly well tolerated.

PMID- 9538363
TI  - [Death by apoptosis of cardiomyocytes: from the cells to clinics].
AB  - Cell hypertrophy, modulations of gene expression or changes of the activity of
      proteins are known to play a role in remodelling of diseased myocardium. However,
      few data are available concerning regulation of the cell mass in heart disease.
      While cardiomyocyte hyperplasia remains controversial and probably constitutes a
      negligible phenomenon, the decreased number of cells could arguably contribute to
      alterations of the pathological myocardium. This loss of myocytes was mainly
      attributed to process of cell necrosis until it was demonstrated that cardiac
      myocytes can also die via apoptosis. This has been observed in ischaemic [1],
      hypertrophic [2], and dilated [3, 4] cardiomyopathy and in arrhythmogenic right
      ventricular dysplasia [5], to mention only the main diseases, and this list
      continues to grow [6]. Apoptosis therefore constitutes a major biological
      phenomenon in cardiology, at least at congresses and in scientific publications,
      but its place and significance in the pathophysiology of heart disease has yet to
      be established.

PMID- 9538364
TI  - [What role to assign for calcium channel blockers in the treatment of arterial
      hypertension in 1997?].
AB  - What is the place of calcium channel blockers in the treatment of hypertension
      (HT)? And, more importantly, what is the place of any molecule recognised as
      being effective to reduce blood pressure figures in the treatment of HT? Beyond
      the hypotheses which have dominated the rational approach up until now,
      suggesting a possible answer to these two questions, medical practice is
      developing towards evidence-based medicine. This opposes two lines of logic:-
      that which argues that the benefit of treatment of HT is exclusively related to a
      reduction of blood pressure figure obtained with the use of the most effective
      molecule or class which is best tolerated in a given clinical context; that which
      argues that it is impossible to prescribe widely and indefinitely molecules whose
      real effect on the clinical prognosis of HT and long-term safety are unknown.
      This new logic no longer recognizes the reduction of blood pressure figures
      independently of the means used to achieve this reduction as the exclusive
      guarantee of the benefit of treatment and proposes that treatments which are
      widely prescribed must have a more detailed clinical evaluation file than that
      authorized by current practice. Calcium channel blockers were recently adopted as
      the main subject of this opposition between two logics, probably because several
      molecules of this class, evaluated in therapeutic trials conducted outside of the
      context of HT, demonstrated harmful cardiovascular effects and that case-control
      studies in the context of HT have indicated the possibility of extracardiac
      adverse effects. It therefore seems useful to try to redefine their place in the
      treatment of HT in the light of this recent debate and, more importantly, to
      extend the discussion to several principles of the pharmacological treatment of
      HT. Leaving current controversies to one side, this review is designed to present
      several elements of these opposing logics.

PMID- 9538365
TI  - [Beta-blockers in cardiac insufficiency].
AB  - This article reviews the information derived from various large-scale multicentre
      studies, summarizes current concepts concerning the mechanisms of action of beta
      blockers in heart failure and recalls their modalities of use in this indication.
      A beneficial effect of beta-blockers on survival has not yet been formally
      demonstrated. However, the promising results of preliminary trials and progress
      in the concepts concerning the mechanism of action of beta-blockers suggest that
      ongoing studies will eliminate any doubts concerning this favourable effect. The
      action of beta-blockers in heart failure has not yet been entirely elucidated.
      The multiple mechanisms proposed are situated at various levels, from the organ
      itself to the subcellular and molecular level. Recent ideas concerning reverse
      remodelling of the ventricle, correction of altered genetic expression and
      protection against apoptosis are interdependent and particularly fascinating. The
      practical use of beta-blockers in this indication is specific and implementation
      of this treatment requires compliance with several rules, the most important of
      which are to start treatment at very low doses and to increase the dosage only
      very gradually.

PMID- 9538366
TI  - [Arrhythmogenic right ventricular dysplasia, torsades de pointes and sudden
      death. New concepts].
AB  - M cells as well as vortex like reentrant tachycardia could explain the torsade de
      pointes pattern leading to sudden death at night in a patient with arrhythmogenic
      right ventricular dysplasia and saddle-back ST segment elevation in lead V2. The
      mechanism of the torsade is explained by the two-dimensional structure of the
      right ventricular free wall reconstructed from paraffin blocks. This case may
      represent a particular form of Brugada's syndrome and cases of sudden death in
      young males in South East Asia.

PMID- 9538367
TI  - [Myocardial infarction in the elderly. Comparison between 2 groups of patients
      over 75 and under 65 years of age].
AB  - To define the clinical characteristics, prognosis and treatment of myocardial
      infarction (MI) in the elderly, we retrospectively compared the files of 101
      patients aged > or = 75 years (mean: 82 +/- 4 years) and of 120 others aged < or
      = 65 years (mean: 55 +/- 4.7 years). The figures corresponding to younger
      patients are presented in brackets. The elderly group included 60.4% women (5%: p
      < 0.001), 58.9% hypertensive subjects (38.3%: p = 0.005); 30.4% diabetics (11.7%:
      p = 0.0013) and 12.6% smokers (66.1%: p < 0.001); 20.8% of the elderly had a
      history of MI (10%: p = 0.002), 15.8% of arteriopathy of the lower limbs (8.3%: p
      = 0.001) and 6.9% of cerebrovascular accident (1.7%: p = 0.02). Elderly patients
      were admitted after an average of 26.6 hours (10.4 hours: p < 0.001). Only 56.4%
      (79.2%) reported typical MI pain, 22.8% (7.5%) had a painless form, 31.8% (4.2%)
      an initial left ventricular failure, 21.8% (7.5%) a global cardiac dysfunction
      and 20.8% (4.2%) a cardiogenic shock (p < 0.001 for all comparisons). 63.4% had
      an anterior MI (40.8%: p < 0.001), 40.6% a Q-form (29.6%: p = NS) and 22.2% an
      atrial fibrillation (0.8%: p < 0.001). Serum myoglobin and total CK
      concentrations were significantly lower in elderly subjects. 20.8% of them
      received beta-blockers (86.7%), 43.6% aspirin (80%), 14.6% oral anticoagulant
      (56.7%), but 63.4% were given diuretics (25.2%) and 31.7% digitalis alkaloids and
      positive inotropic drugs (6.7%) (p < 0.001 for all these comparisons). Heparin,
      nitrates, calcium channel blockers, ACE inhibitors and antiarrhythmics were
      prescribed as often regardless of age. Only 10 elderly patients (9.9%) were
      treated with thrombolytics (77: 65%: p < 0.001); 6 (5.9%) underwent coronary
      angiography (43: 35.8%: p < 0.001), 2 (2%) angioplasty (11: 9.2%) and one (1%)
      coronary bypass surgery (12: 10%). 35 elderly patients (34.7%) died while in
      hospital (5: 4.2%), 22 suddenly, 10 in cardiogenic shock and 3 due to
      arrhythmias. 38 cases (37.8%) of heart failure (21: 17.5%), 21 (20.8%)
      recurrences of coronary insufficiency (8: 6.7%) and 11 (10.9%) mechanical
      complications of MI (4: 3.3%) were also observed (p < 0.001 for all these
      comparisons). Due to lack of sufficient data, we could not define the status of
      the surviving patients discharged from hospital. The wider use of thrombolytics,
      angiography and angioplasty (coronary bypass surgery still having a heavy
      mortality and morbidity) is probably the best way to improve the prognosis of MI
      in the elderly.

PMID- 9538368
TI  - [Evaluation of the cost of a systematic early reperfusion of the infarction
      artery by primary or salvage angioplasty].
AB  - In order to evaluate the cost of a strategy designed to ensure a maximal early
      patency rate of the coronary artery responsible for acute myocardial infarction,
      we retrospectively studied 112 unselected, consecutive patients, treated during
      the 6 hours following onset of symptoms, either by intravenous thrombolysis
      (group 1, n = 57) followed by coronary angiography at the 90 th minute, and if
      necessary rescue angioplasty, or by primary angioplasty (group 2, n = 49), or
      finally by simple conventional medical treatment (group 3, contraindications to
      thrombolysis and catheterization, n = 6). The costs of medical treatment were
      expressed as standard mean costs, and were compared with total hospital
      expenditure. The overall hospital mortality was 8.0%: 3.5% in group 1, 8.2% in
      group 2, and 50% in group 3. The total cost of medical procedures during the
      initial hospital stay was 16,684 F, identical in groups 1 and 2 (17,985 F and
      16,780 F, respectively). Total hospital expenditure was 36,254 F, with no
      significant difference between groups 1 and 2 (34,086 F and 41,670 F,
      respectively), despite a tendency towards a higher cost in group 2. This tendency
      reflected that of a longer hospital stay for patients in group 2, due to their
      more severe condition, but the proportion of medical cost within the total
      hospital expenditure was lower than in group 1 (40% and 53%, respectively). After
      one year of follow-up, only one other death from a cardiac cause was reported:
      the supplementary expenditure amounted to 14,617 F. This maximal reperfusion
      strategy during the acute phase of myocardial infarction achieved a low hospital
      mortality and one-year mortality, without a marked excess medical cost compared
      to previously published estimations. Primary angioplasty appears to have allowed
      a certain reduction of this cost compared to thrombolysis, but the heterogeneity
      of the study population does not allow direct comparison of the costs of the 2
      reperfusion methods. One half of the total expenditure remains directly dependent
      on the duration of the hospital stay.

PMID- 9538369
TI  - [Evaluation of the cost of a systematic early reperfusion of the infarction
      artery by primary or salvage angioplasty].

PMID- 9538370
TI  - [Factors determining the improvement of effort capacity in aged patients with
      coronary disease during the 1st month following coronary surgery].
AB  - In order to determine the predictive factors of improvement of the physical
      capacity of elderly coronary patients following coronary surgery, we
      retrospectively analysed the data of 204 consecutive patients over the age of 65
      years (181 men, 23 women, mean age: 70 +/- 4.4 years), admitted for a phase II
      active training programme. METHODS: The patients were divided into two groups as
      a function of the rate of improvement of the duration of the stress test: group A
      (improvement greater than or equal to 25%; n = 108) and group B (less than 25%; n
      = 96). Comparison of these 2 groups by multivariate analysis identified
      predictive factors of improvement among seven variables: age, sex, excess weight,
      haemoglobin, number of training sessions, duration of baseline stress test,
      interval between bypass graft and start of training. RESULTS: After training, the
      duration of the stress test and the maximal power were improved by 26.5% and 24%,
      respectively: 7.1 +/- 1.7 vs 8.9 +/- 2.3 minutes (p = 0.0001); 79 +/- 18.4 vs
      97.8 +/- 23.7 watts (p = 0.0001). 34 (1.4%) of the 2,396 training sessions were
      temporarily interrupted, because of muscle fatigue in 47% of cases. Patients who
      had readapted before the 15th postoperative day presented fewer incidents: 4.3%
      vs 13.1%; NS. Only three variables appeared to be predictive of improvement of
      physical capacity: a duration less than 6 minutes on the baseline stress test (p
      = 0.0003), more than 12 training sessions (p = 0.0029) and age less than or equal
      to 70 years (p = 0.014). CONCLUSION: In elderly subjects undergoing coronary
      surgery, the improvement of physical capacity is greater the lower the baseline
      effort, the lower the age-group and the greater the number of training sessions.
      In the absence of contraindication, it appears justified to include elderly
      coronary patients in training programmes, even when their baseline effort level
      appears to be low. This training can be started by the 15th postoperative day.

PMID- 9538371
TI  - [Cardiovascular readaptation after aortocoronary bypass, in patients over 65
      years of age?].

PMID- 9538372
TI  - [VDD mode single electrode cardiac stimulation: indications, results and
      limitations of the method].
AB  - Several authors have reported the single atrioventricular (AV) electrode,
      comprising an atrial dipole floating in the right atrium, to be a system capable
      of providing results which are just as satisfactory as those of conventional
      systems (DDD). Between August 1992 and March 1995, a VDD single electrode
      pacemaker was implanted in 65 patients (mean age: 73 years +/- 17.2). The
      indication for implantation was isolated high degree AVB with no apparent sinus
      dysfunction. Four pacemakers were used: Vitatron (n = 24), Intermedics (n = 23),
      Medico (n = 13), Biotronik (n = 5). Intraoperative atrial endocavitary recording
      was 1.8 mV +/- 0.74. 17 patients died from a cause unrelated to pacemaker
      dysfunction. 4 patients were lost to follow-up. The remaining 44 patients were
      reviewed in our centre with a mean follow-up of 14.5 months +/- 7 months. Seven
      pacemakers (16%) were reprogrammed in VVI or VVI (R) mode, because of permanent
      atrial fibrillation in 3 cases, complete loss of atrial reception in 2 cases and
      late onset sinus dysfunction in 1 case. In the 41 patients in sinus atrial
      rhythm, the atrioventricular synchronization rate was greater than 90% in 88% of
      patients, equal to 76.3% in 2.4% of patients and atrioventricular synchronization
      was impossible in 9.6% of cases. CONCLUSION: The overall results of our
      preliminary experience of VDD mode single electrode pacemaker are moderate. The
      poor results essentially concerned patients with paroxysmal atrial arrhythmias
      prior to pacing.

PMID- 9538373
TI  - [Adams-Stokes syncope disclosing a crisis of rheumatic fever. Apropos of a case].
AB  - A high degree atrioventricular block (AVB) is an exceptional finding during an
      acute episode of rheumatic fever (RF). The authors report a case of complete
      syncopal AVB requiring a temporary pacemaker, representing the first episode of
      RF.

PMID- 9538374
TI  - [Primary hyperaldosteronism. Apropos of 2 cases].
AB  - Primary hyperaldosteronism (PHA) represents less than 1 to 2% of all causes of
      hypertension (HT). We report 2 cases of primary hyperaldosteronism which
      emphasize the difficulty of distinguishing neoplastic PHA from idiopathic PHA,
      observed in a 60-year-old woman and a 42-year old woman, respectively. In both
      cases, the diagnosis of PHA was suggested by marked hypokalaemia with
      inappropriate potassium excretion and was confirmed by hyperaldosteronaemia and
      low and poorly stimulated renin activity. In the first case, computed tomography
      showed nodular hyperplasia of the 2 adrenal glands. The patient was treated with
      spironolactone and calcium channel blockers which controlled blood pressure and
      serum potassium. In the second case, computed tomography and magnetic resonance
      imaging revealed an adrenocortical adenoma confirmed by pathological examination
      after the operation. The diagnosis of primary hyperaldosteronism is based on
      three steps: detection, positive diagnosis and aetiological diagnosis. Detection
      is essentially based on demonstration of hypokalaemia. Positive diagnosis is
      based on demonstration of elevated aldosterone secretion with inhibited renin
      secretion. The aetiological diagnosis is dominated by the differentiation between
      Conn's adenoma and bilateral adrenal hyperplasia, which has therapeutic
      implications.

PMID- 9538375
TI  - [Comparison of anti-ischemic effect of bepridil and diltiazem evaluated by
      exercise test in patients with coronary disease. A multicenter study. Groupe
      d'Investigateurs].
AB  - Bepridil (Cordium) is a calcium channel blocker which has been demonstrated to be
      effective in the preventive treatment of angina. Few controlled trials have
      compared bepridil to diltiazem (Tildiem), the reference calcium channel blocker.
      The objective of this study was to evaluate the efficacy and safety of bepridil
      in stable coronary patients. 148 patients (139 M, 9 F, mean age: 58 +/- 8.6
      years), with documented coronary artery disease and positive stress test after 5
      days of placebo were included. After double-blind randomization, they received
      bepridil (300 mg/day ion 3 doses), or diltiazem (180 mg+/day in 3 doses) for 15
      days. A stress test was then performed under the same conditions as on inclusion.
      The anti-ischaemic efficacy of the two drugs was comparable. Total work increased
      from 4,552.4 +/- 2,179.4 Kpm a 6,103.2 +/- 2,849.2 Kpm with bepridil (p < or =
      0.0001) and from 4,524.8 +/- 2,160.5 Kpm a 5,848.3 +/- 2,800.3 Kpm (p < or =
      0.0001) with diltiazem, with no intergroup difference. Duration of effort was
      significantly prolonged: from 10.5 +/- 3.0 min to 12.5 +/- 3.3 min with bepridil
      (p < or = 0.0001) and from 10.5 +/- 2.9 min to 12.1 +/- 3.4 min with diltiazem (p
      < or = 0.0001), with no intergroup difference. The time to onset of 1 min of ST
      depression increased significantly between the two stress tests, from 8.36 +/-
      2.7 min to 10.82 +/- 3.4 min with bepridil (p < or = 0.001) and from 8.02 +/- 3.0
      min to 10.53 +/- 3.6 min with diltiazem (p < or = 0.001), with no significant
      difference between the two groups. The clinical safety of the two products was
      comparable. On the electrocardiogram, the QT interval was significantly prolonged
      with bepridil, from 368.6 +/- 37.5 msec to 393.6 +/- 38.7 msec (p < or = 0.0001),
      reflecting cellular impregnation of the drug.

PMID- 9538376
TI  - Aspirin for prevention of myocardial infarction. A double-edged sword.
AB  - BACKGROUND: The use of low dose aspirin is associated with upper gastrointestinal
      bleeding, especially in the elderly. Anemia is one of the risk factors of acute
      myocardial infarction especially in patients with ischemic heart disease. METHODS
      AND RESULTS: We present a series of fifteen patients treated with low dose
      aspirin for secondary prevention of ischemic heart disease who had upper GI
      bleeding and were admitted to our hospital because of unstable angina or
      myocardial infarction. Nine patients had acute myocardial infarction and six
      patients had unstable angina. The mean age of the patient was 72 +/- 9 years.
      Only two patients had a previous history of duodenal ulcer before their
      admission. The duration of aspirin therapy ranged from a few days to more than a
      year. Weakness, abdominal pain and melena were present in most of the patients
      between 2-7 days before the appearance of chest pain, and syncope was the chief
      complaint in 5 patients. CONCLUSIONS: We conclude that aspirin which is given to
      patients in order to prevent myocardial infarction might cause myocardial
      infarction as a sequella of upper gastrointestinal bleeding. Lack of patient
      education was the primary cause of the delayed diagnosis of this complication.
      Instruction of patients treated by aspirin to seek medical advise because of
      symptoms of gastrointestinal bleeding could prevent acute myocardial infarction
      in patients treated by aspirin who have upper gastrointestinal bleeding.

PMID- 9538377
TI  - Hurthle cell tumors.
AB  - OBJECTIVES: a) To provide a clinicopathological profile of Hurthle cell neoplasms
      (HCT) in our experience. b) To evaluate if there are any differences in the
      clinical or morphological features between three HCT categories: benign,
      malignant and indeterminate. c) To examine the role of the clinical and
      morphological features in predicting the behavior of these neoplasms. METHODS: We
      reviewed the clinical reports of all patients with a histological diagnosis of
      HCT at our Hospital between 1981 and 1996. The final study group consisted of 25
      cases. The neoplasms were divided into three categories on the basis of presence
      and degree of capsular and vascular invasion, marked nuclear atypia, tumour
      necrosis and pattern of growth. A series of clinical parameters were evaluated.
      RESULTS: Of the 25 tumors, 52% were morphologically classified as benign, 8% as
      indeterminate and 40% as malignant. Follow-up ranged from 10 months to 14.8 years
      or until death (average 3.8 years). There were four local recurrences (20%),
      three in the malignant group (30%) and one in the benign group (7.6%) (p = 0.15).
      One patient presented metastases and died because of tumor during the follow-up.
      Apart from capsular and vascular invasion and some aspects of therapy, no
      significant differences were found in the clinical and histological parameters
      analyzed between the three histological groups or between the groups with or
      without recurrence. CONCLUSION: We did not find any clinical or morphological
      parameter which can predict recurrence among these tumors. Our study further
      establishes the controversial issues surrounding the biological behavior of
      Hurthle cell neoplasms.

PMID- 9538378
TI  - Magnesium fortification of water. A possible step forward in preventive medicine?
AB  - Magnesium is an essential cation for more than 300 enzymes in our body. Among
      them, it is a cofactor for ATP metabolism. Diverse clinical manifestations have
      been reported in conjunction with Mg++ deficiencies, including sudden death,
      accelerated atherosclerosis, asthma, neurologic and even psychiatric clinical
      entities. Limited previous studies with Mg++ supplementation have shown to be of
      a large preventive advantages. We summarize the current literature concerning
      Mg++ supplementation and recommend to do so on national basis adding magnesium to
      the water supplies of large areas.

PMID- 9538379
TI  - [Anatomo-clinical conference. Pitie-Salpetriere Hospital. Case No 2--1997.
      Recurrent febrile pancytopenia].

PMID- 9538380
TI  - [C5-C6 peripheral neuropathy disclosing Horton disease].

PMID- 9538381
TI  - [Aplastic anemia and pregnancy: a new case].

PMID- 9538382
TI  - [Lymphatic dysplasia and agenesis of the inferior vena cava].

PMID- 9538383
TI  - [Primary sclerosing colangitis and sarcoidosis].

PMID- 9538384
TI  - [Tracheal actinomycosis: a case].

PMID- 9538385
TI  - [For an evidence-based complementary medicine].

PMID- 9538387
TI  - [Week-long hospitalization in a Department of Internal Medicine: patients and
      care patterns. Description and comparison with standard hospitalization].
AB  - OBJECTIVES: The objective of this study was to determine the inpatient and care
      pathway predictive factors of week hospitalization (week-end excluded = HDS)
      compared to classical short term hospitalization (HC). METHODS: We compared 340
      HDS stays to 65 HC stays. We analyzed the major in-patient sociodemographic and
      medical characteristics, and their care pathways. RESULTS: HDS inpatients were
      younger, more living in couples, had a higher educational level, better social
      insurance, more cancer, less associated diagnosis, less general health impairment
      than HC in-patients. More chemotherapies and endoscopies were performed in HDS.
      Hospital physicians were more often involved in HDS admissions than in HC
      admissions and general practitioners were more often involved in outpatient
      hospital visits for advice before HDS hospitalization than before HC
      hospitalization. HDS hospitalizations per in-patient were more numerous than HC
      hospitalizations. HDS inpatients were discharged directly to their home more
      often. After logistic regression modeling, most of these factors remained
      independently associated with HDS hospitalization, except for sociodemographic
      characteristics, age excluded, admission rates and home discharge. CONCLUSIONS:
      Type of hospitalization (HDS vs. HC) was mainly determined by medical
      characteristics of patients and by care pathways. Limiting factors were mainly
      due to organization of care.

PMID- 9538386
TI  - [Acquired hemophilia caused by autoantibodies against factor VIII coagulation
      activity. Clinical, biological study and therapeutic indications. Experience
      based on a study of 9 cases].
AB  - STUDY DESIGNS: To describe retrospectively the experience of the Internal
      Medicine and Clinical Hematology Departments of a University Hospital on adult
      acquired hemophilia (AH) caused by autoantibody against factor VIII coagulant
      (f.VIII:C) activity. Diagnosis, clinical datas, associated diseases, treatment
      and final outcome are described and compared to the published literature.
      MATERIAL AND METHODS: All cases admitted in both departments since 1989 were
      enrolled in the study. Clotting analyses comprised clotting times (activated
      partial thromboplastin time, prothrombin and thrombine times), measurements of
      f.VIII:C level, antifactor VIII detection and measurement by the Bethesda method
      assay, Search for an etiologic factor could not be standardized. All patients
      were followed until cure, sustained improvement, or death. RESULTS: From 1989 to
      1996, AH was diagnosed in nine adult patients. Mean age was 76 +/- 24.6 years
      (range : 65-89) and sex ratio male to female was 2. Eight bleeding episodes
      occurred in seven patients, resulting consistently in severe hemorrhagic anemia
      and leading to hemodynamic failure in two, while two others remained asymptomatic
      for prolonged periods. The initial levels of f.VIII:C ranged from less than 1% to
      20%, and the titers of inhibitors ranged from 0.5 to 100 Bethesda units. An
      underlying disease, to which the appearance of their inhibitor could be related,
      either concomitantly or up to 1 year later, was found in four cases including
      (one case each): rheumatoid arthritis, lupus erythematosus with antiphospholipid
      syndrome, followed by non-Hodgkin malignant lymphoma, relapsing carcinoma and,
      biliary tract surgery. Six acute bleeding episodes necessitated symptomatic
      measures, based on activated prothrombin complex concentrates in four instances,
      with a good response in all cases. Preparation to minor surgical operations was
      achieved in two asymptomatic subjects by either highly purified factor VIII
      concentrations infusion or intravenous 1-desamino-8-D-arginine vasopressin, with
      a good control of local hemostasis in each case. Three received intravenous
      immunoglobulins, which resulted in success in one, failure in one and,
      questionable response in the latter. Immunosuppression, mainly with
      corticosteroids, cyclophosphamid, or both, was given to seven, resulting in
      disappearance of inhibitor in five (delay to cure ranged from 2 weeks to 10
      months), improvement in one, and failure in one (in this latter case, cure was
      eventually achieved with the anti-Hodgkin disease MOPP chemotherapy). After a 27
      month mean follow-up, six patients experienced a sustained complete response and
      one a sustained partial response to immuno-suppression, two untreated patients
      remained asymptomatic, two died later from malignancy (carcinoma and
      myelodysplastic syndrome). CONCLUSION: AH usually presents as a severe or even a
      life-threatening disease, necessitating prompt and thorough symptomatic measures
      directed at the cessation of bleedings and prevention of their relapse. In our
      experience, no death was attributable to AH or its treatment. Immunosuppression
      is useful in selected cases, but must be carefully discussed, since it can be
      highly toxic, especially in the elderly. Given the possibility of a delayed onset
      of some etiologic factors, a prolonged surveillance of each case of idiopathic AH
      is mandatory.

PMID- 9538388
TI  - Retinoids and metastatic renal cell carcinoma.
AB  - The treatment of metastatic renal cell carcinoma remains unsatisfactory. Several
      therapeutic trials with retinoids and r interferon alpha (r IFN alpha) suggest a
      synergic antiproliferative effect between retinoid acid and r IFN alpha.
      Pharmacokinetic data and the mechanism of antiproliferative effects of retinoids
      are discussed. The induction of growth arrest is related to the expression of
      specific retinoid receptors. Further investigations are required in order to
      target the patient population which requires this therapy.

PMID- 9538390
TI  - [CD4 lymphocytopenia, Gougerot-Sjogren and systemic lupus erythematosus].

PMID- 9538389
TI  - Efficacy of teicoplanin in Staphylococcus aureus catheter-related tricuspid
      endocarditis during severe neutropenia.

PMID- 9538391
TI  - Are long-term plasma exchanges and ciclosporin useful in the management of severe
      chronic respiratory failure due to myasthenia gravis?

PMID- 9538392
TI  - [Interstitial pneumopathy caused by atenolol: a new case].

PMID- 9538393
TI  - [Hemiballism with manic access caused by toxoplasmic abscess in AIDS].

PMID- 9538394
TI  - [Neurologic complications of atrophic polychondritis].

PMID- 9538395
TI  - [Black widow bites. 3 cases].

PMID- 9538396
TI  - [Valvulopathy of patients in chronic hemodialysis].

PMID- 9538397
TI  - Severe valvular heart disease in patients on chronic dialysis. A five-year
      multicenter French survey.
AB  - A retrospective multicenter survey of the 230 chronic dialysis centers in
      metropolitan France, conducted between January 1 1998 and December 31 1992, to
      assess the incidence, causes and features of severe valvular heart disease among
      chronic dialysis patients, identified 98 patients. The annual incidence was
      estimated to be 15 to 19 cases per 10,000 dialysed patients. The most common
      etiologies were calcific valvular disease (69%) and endocarditis (19%). Calcific
      valvular disease led mostly to aortic stenosis, whereas endocarditis primarily
      caused mitral insufficiency. Two valves were damaged in 32% of the endocarditis
      patients versus 9% of those with calcific valvular disease. Sixty-one patients
      underwent surgery. Median overall survival after surgery was 25 +/- 3.0 months.
      Patients who underwent surgery for calcific valvulopathy, aortic stenosis or only
      aortic valve replacement had a median survival of 36 months. Patients who
      underwent surgery for endocarditis or replacement of 2 valves had a median
      survival of < 12 months. Actuarial survival of surgical patients differed
      significantly between: i) the patients for whom presurgical evaluation showed a
      single valvular lesion and those with multiple valvular lesions (p = 0.002), ii)
      the patients who had surgery to replace a single heart valve and those who had
      another type of surgery (p = 0.001), and iii) the patients who had surgery to
      insert a single aortic prosthetic heart valve and those who had another type of
      surgery (p = 0.004). Multivariate analysis (including etiologies, number of
      valvular lesions and type of surgery) showed that survival was significantly
      dependent only on the number of severe valvular lesions (p = 0.002). Five
      patients with severe calcific aortic stenosis died before scheduled surgery could
      be performed. These data suggest that, for patients on chronic dialysis, calcific
      aortic stenosis is the most frequent form of severe valvular disease. Because
      aortic stenosis progresses rapidly in these patients and thus quickly leads to
      irreversible cardiac failure, the operative risk, although high in this
      population, seems acceptable when only one valve is affected.

PMID- 9538399
TI  - Genital herpes: epidemiology and pathophysiology. Update and new perspectives.
AB  - Genital Herpes simplex virus (HSV) is a sexually transmitted disease (STD) which
      affects millions of people worldwide and is mainly due to HSV type 2.
      Seroprevalence rates as high as 60-90% have been reported in developing
      countries. In developed countries, 20% of the general population is HSV2
      seropositive. Recent epidemiological surveys employing type-specific antibody
      assays show that the prevalence of HSV-2 infections is rising at an alarming
      rate. Also, the epidemiology is changing with an increasing incidence of first
      episodes caused by HSV-1. The natural history of HSV infection includes acute or
      subclinical first episode mucocutaneous infection, establishment of neuronal
      latency, and intermittent virus reactivation with or without associated symptoms.
      Although this sequence of events has been recognized for more than five decades,
      little is known about the exact mechanism of latency and reactivation. Almost all
      persons with HSV2 infection will have recurrences. Recent data show that many of
      these infections are subclinical: subclinical shedding can be documented in over
      80% of HSV2 seropositive individuals who deny subclinical lesions. This suggests
      that patients shed virus and transmit it even in the absence of clinical signs
      and that genital herpes should be redefined as a chronic rather than an
      intermittent disease.

PMID- 9538398
TI  - [Treatment with cyclosporine of severe colitis in hemorrhagic rectocolitis.
      Apropos of 7 cases].
AB  - Cyclosporin has been suggested as an alternative treatment in severe acute
      ulcerative colitis. In a retrospective study, the outcome of seven ulcerative
      colitis patients treated by intravenous cyclosporin (mean dose 3.6 mg/kg/day) has
      been evaluated. Short-term results indicated full remission in 3/7 (43%)
      patients. At long term follow-up (one year), only 2/7 patients could avoid ileal
      pouch-anal anastomosis. Two complications (one colonic perforation and one
      septicemia) were observed. Our results suggest that intravenous cyclosporin
      should not be recommended as a standard therapy in severe acute ulcerative
      colitis. Its use has to be limited in patients presenting a major
      contraindication for surgery and has to be performed by those experienced in both
      immunosuppressive treatment and inflammatory bowel disease.

PMID- 9538400
TI  - [Prognostic factors of multiple myeloma].
AB  - Multiple myeloma is a heterogeneous disease with survival ranging from a few
      months to many years. Several clinical parameters (S beta 2-M) are a direct
      expression of the tumor burden and have been shown by univariate analysis to be
      related to patient survival. Durie and Salmon developed a myeloma staging system
      that analyzed the presenting clinical features, response to treatment and
      survival duration. But this classification is not related to the intrinsic
      malignancy (labeling index). Many new parameters (genetic alterations, plasma
      cell evaluation; serum marqueurs, immune dysregulation) related to patient
      response to chemotherapy and survival duration have been identified. However,
      they have not yet been included in standard staging and compared with the
      recognized prognostic parameters in multivariate analysis. There is a need to
      create a new international myeloma staging system based on biological features of
      the disease.

PMID- 9538401
TI  - [ANCA (antineutrophil cytoplasmic antibodies). Contribution of ANCA to the
      understanding of pathogenic mechanisms of systemic vasculitis].
AB  - ANCA (antineutrophil cytoplasmic antibodies) are a growing class of interest;
      these antibodies target lysosomial enzymes from polymorphonuclear cells. They
      represent diagnosis tools and prognosis markers in systemic vasculitis (Wegener's
      granulomatosis and microscopic polyangiitis). They are also detected in other
      chronic inflammatory diseases as lupus and rheumatoid arthritis. Their
      description, ten years ago, led to a huge amount of clinical and experimental
      work. The role of ANCA as pathogenic auto-antibodies in the disease is supported
      in numerous studies giving new insights into the pathogenesis of systemic
      vasculitis.

PMID- 9538402
TI  - [Images suggestive of hepatic metastases: value of MRI with fat saturation].

PMID- 9538403
TI  - [Anatomo-clinical conference. Pitie-Salpetriere Hospital. Case No 3--1997.
      Febrile pancytopenia].

PMID- 9538404
TI  - [Specific bronchial sites of Mycobacterium kansasii in 2 patients with human
      immunodeficiency virus infection].

PMID- 9538405
TI  - [Edema of the face as the initial sign of Horton disease. Apropos of 2 cases].

PMID- 9538406
TI  - [Systemic vasculitis and alpha-1 antitrypsin deficiency of type PiZZ: report of a
      case].

PMID- 9538407
TI  - The varying faces of thrombotic thrombocytopenic purpura.

PMID- 9538408
TI  - [Thrombotic thrombocytopenic purpura and hemolytic-uremic syndrome in adults.
      Apropos of 27 cases].
AB  - We report a series of 27 patients included on the basis of either thrombotic
      microangiopathy (TMA) at renal histology (13 cases) or, in the absence of
      histology, non-immunological hemolytic anemia with schizocytes and thrombopenia
      (14 cas). The etiopathogenic treatment consisted in the administration of
      antiagregating agents (in all patients except 3 of group I because of the
      severity of thrombopenic), corticosteroids (1 case), intravenous immunoglobulins
      (2 cases) fresh frozen plasma (FFP) without plasma exchange (PE) in 7 cases and
      PE with FFP in 13 patients. According to the 6 months outcome, 4 groups were
      considered I: death due to neurological damage; II: chronic hemodialysis; III:
      partial renal recovery; IV: complete renal recovery. COMMENTS AND CONCLUSIONS:
      a/Patients with neurological complications have poor prognosis in spite of minor
      renal involvement and use of PE whose indication is validated in these cases.
      b/When renal involvement predominates, accelerated hypertension is linked to
      arteriolar or mixte type of TMA, exposes to an increased risk of hemorrhagic
      complications of the renal biopsy (4 out fo 5) which questions the usefulness of
      such biopsy (group II). c/TMA may precede cancer. It has per se a favorable
      outcome even when metastases are already present, warranting aggressive
      treatment.

PMID- 9538409
TI  - [Epstein-Barr virus and associated diseases. Course of Medical Virology, Institut
      Pasteur, 1995/1996].
AB  - The Epstein-Barr virus (EBV) is an ubiquitous virus infecting nearly the entire
      adult human population. The EBV is closely associated with rhinopharyngeal cancer
      in Southern China and Northern Africa. Three geographic subtypes of EBV have been
      identified to date. They differ by their nuclear antigene EBNA2. The EBNA2 AC
      strains predominate in Asia; EBNA2 AD strains predominate in the United States;
      EBNA2 B strains have all been identified in black Africa. Burkitt's lymphoma is
      the most frequent tumor in children aged 5 to 9 years in equatorial Africa. A
      prospective study in 42,000 children in Ouganda demonstrated that children who
      develop Burkitt's lymphoma have severe EBV infection during the first months of
      life. Very early EBV infection observed in North or equatorial Africa increases
      the risk of Burkitt's lymphoma by 20-times that in Europe. Hyperendemic malaria
      observed in the equatorial zone increases the incidence of tumors by a factor of
      20. An association between EBV and rhinopharyngeal cancer is a constant feature
      only in South China, in North and East Africa, as well as in arctic regions as
      cases of carcinoma not associated with EBV infection have been reported in
      Greece. Surveys in the Democratic Republic of China concerning several hundred
      thousand persons have shown that serum IgA/VCA allows early diagnosis of cancer.
      It is estimated that the risk of rhinopharyngeal cancer is 20% in Chinese with
      high levels of IgA/VCA.

PMID- 9538411
TI  - [Epstein-Barr virus].
AB  - The Epstein-Barr virus (EBV), which predominantly infects B-cells, has certain
      novel features, particularly its ability to remain latent for long periods and
      its capacity for transformation. Host immune response is complex, varying in
      intensity and quality. Disease expression results from this conflict between the
      host and the virus. Clinical manifestations are thus quite variable, ranging from
      asymptomatic infection, or various aspects of infectious mononucleosis, to
      malignant lymphoproliferation. This is a perfect illustration of the transition
      between benign and malignant reactive lymphoproliferation and of the organism's
      capacity to produce a more or less rapid and effective response to a potentially
      malignant disorder.

PMID- 9538410
TI  - [Epstein-Barr virus and cellular immortalization].
AB  - Epstein-Barr virus has been associated to several forms of neoplasia including
      Burkitt's lymphoma, B lymphomas in immuno-compromised patients and
      undifferentiated nasopharyngeal carcinoma. Immunodepression, genetic and/or
      environmental factors and the expression of several viral genes (latent genes
      mainly) may contribute to these pathologies. In vitro, several latent proteins
      (EBNA 1, 2, 3A, 3C, 5 et LMP-1) directly or indirectly contribute to the
      initiation and maintenance of the transformation process. The role of these
      proteins is discussed in the present article.

PMID- 9538412
TI  - [Epstein-Barr virus and post-transplantation lymphoproliferations].
AB  - Host immunity to Epstein-Barr Virus Patterns of Epstein-Barr Virus latent gene
      expression in EBV posttransplantation lymphoproliferative disorders Cytokines
      network in posttransplantation lymphoproliferative disorders associated with EBV
      Lymphomagenesis and EBV Morphology and clonality of posttransplantation
      lymphoproliferative disorders associated with EBV Treatment of
      posttransplantation lymphoproliferative disorders associated with EBV.

PMID- 9538413
TI  - [Therapeutic prospects and lymphoproliferative syndromes related to EBV].
AB  - The B lymphoproliferative disorders are a major (10%) and severe (70% mortality)
      complication of immunosuppression required for HLA-mismatched bone marrow or
      organ transplantation. An experimental model was developed in which patients
      infected EBV-B cells are inoculated into scid mice and develop into tumors,
      allowing evaluation of treatment efficacy: monoclonal antibodies directed to
      membrane antigens of tumoral cells (monoclonal antibodies anti-B), monoclonal
      antibodies neutralizing interleukins (and especially IL6), cytotoxic T cells.
      Results obtained with these three different approaches are herein reported.

PMID- 9538415
TI  - [Anatomo-clinical conference. Hopital de la Pitie-Salpetriere. Case No 1--1997.
      Peripheral neuropathy and cervical adenopathy in a 58-year-old diabetic patient].

PMID- 9538414
TI  - [Human herpesvirus 8].
AB  - Human herpesvirus 8 (HHV-8, KSHV) is a novel virus for which fragments of genomic
      sequence were identified in 1994. This was done by means of a differential
      amplification technique applied to the DNA of Kaposi's sarcoma lesions and normal
      tissues obtained from the same individual. The analysis of nucleotide sequence
      has shown that HHV-8 is closely related to herpesvirus saimiri and Epstein-Barr
      virus, two members of Gammaherpesvirinae sub-family. The virus has been observed
      by means of electron microscopy in chronically infected cell lines. Serological
      studies are still preliminary but seem to demonstrate a low prevalence of HHV-8
      infection among the general population at least in Western countries, HHV-8 is
      mainly detected by means of polymerase chain reaction (PCR) and molecular
      hybridization. HHV-8 detection in human tissues is strongly associated with three
      diseases: Kaposi's sarcoma, body-cavity-based lymphomas and Castleman's disease.
      The demonstration of the causative role of HHV-8 in the occurrence of these three
      diseases, particularly Kaposi's sarcoma, would have major consequences for their
      diagnosis and treatment.

PMID- 9538416
TI  - [Drug-induced xerostomia].
AB  - Hyposalivation is related to decreased salivary flow, with xerostomia as an
      ultimate degree. Prolonged severe hyposalivation or xerostomia may induce oral
      pain, poor tolerance to dentures, loss in taste acuity and increased incidence of
      oral infections: gingivitis, periodontitis, oral candidosis, infectious
      sialadenitis and multiple dental caries. Most of the time hyposalivation is a
      reversible drug-induced side-effect. Hyposalivation is frequent, particularly in
      elderly people with numerous drugs prescribed on a long-term continuous basis,
      and in psychiatric patients. It remains a neglected clinical problem. Besides the
      well-known antimuscarinics, antihistaminics, imipraminic antidepressants and
      phenothiazic neuroleptics, many drugs may induce hyposalivation. This work aims
      to review drug-induced xerostomia in 1997 (French pharmacopeae), and high-risk
      associations.

PMID- 9538417
TI  - [HTLV I virus infection disclosed by recurrent scabies associated with genital
      condylomatosis].

PMID- 9538418
TI  - [Evaluating the prevalence of patients at risk of Creutzfeldt-Jakob disease in
      Internal Medicine (criteria of the DGS)].

PMID- 9538419
TI  - [Salmonella meningitis in children in Libreville. Retrospective study of 9
      cases].
AB  - BACKGROUND: Salmonella meningitis is a rare entity, even in tropical area where
      salmonellosis is common. Its prognosis is poor and the choice of adequate
      antibiotic therapy is difficult. PATIENTS AND METHODS: The files of nine children
      (three boys, six girls) admitted to the pediatric unit of the Owendo Pediatric
      Hospital in Libreville for salmonella meningitis between January 1, 1989, and
      December 31, 1993 were retrospectively studied. Diagnosis was established by a
      positive culture of cerebrospinal fluid. RESULTS: Salmonella was the third cause
      (8.65%) of purulent meningitis observed during this period. Eight children were
      less than 1-year old, seven were from low socioeconomic standard families. The
      main clinical manifestations were fever (seven cases), pallor (six cases),
      diarrhea (four cases), nuchal rigidity (four cases), convulsions (three cases)
      and bulging fontanel (three cases). Five children (55.5%) were severely anemic
      (hemoglobin < 5 g/dL) but none had abnormal hemoglobin. Serotyping could not be
      performed in any case. Salmonella isolates were resistant to chloramphenicol in
      six cases and to ampicillin in five. Cefotaxime (200 mg/kg/24 h intravenously in
      three divided doses) was given to seven patients. The duration of therapy was at
      least 3 weeks in four patients. There were five deaths at ages ranging from 1 to
      12 months, ie, a case fatality rate of 55.5%. Three patients (33.3%) recovered
      with neurological sequels. CONCLUSION: The prognosis of salmonella meningitis is
      poor, even in the case of prompt diagnosis and adequate therapy. Preventive
      measures only can decrease the risk of illness in children.

PMID- 9538420
TI  - [Morphological anomalies of breasts in adolescent girls and their surgical
      correction].
AB  - BACKGROUND: Morphological anomalies of the breast in adolescent girls cause
      considerable psychological distress. Plastic and reconstructive surgery offer the
      possibility of improving such conditions. The aims of this work were to define
      and illustrate the various types of anomalies, clarify their distribution and
      present the repair methods that can be used and the results obtained. POPULATION
      AND METHODS: A consecutive series of 33 girls under the age of legal majority,
      admitted over a 1-year period for surgical modifications of breast shape, was
      studied. The basic anomalies were classified as mammary hypertrophy, hypotrophy,
      asymmetry, and abnormal shape, among which were Poland's syndrome, tuberous
      breasts, thelorism and pute ptosis. The basic techniques used were reduction,
      augmentation with placement of an implant and breast remodeling. Distribution of
      anomalies was as follows: symmetrical bilateral hypertrophy, 33%; asymmetric
      bilateral hypertrophy, 30%; unilateral hypertrophy, 6%; combined hyper- and
      hypotrophy, 3%; unilateral hypotrophy with abnormal shape, 9%; abnormal shape
      with normal size, 15% and bilateral hypotrophy, 0.3%. Mean hospital stay was 3
      days and there were no serious postoperative complications. DISCUSSION: Bilateral
      hypertrophy was the most frequent disorder and the main drawback was residual
      scaring. Bilateral hypotrophy was rarely seen since only congenital absence of
      mammary glands is surgically treated before legal coming of age. The main problem
      of implants was formation and contraction of fibrous capsules around the implants
      in 5% of cases. Asymmetry and anomalies of shape were more difficult to treat
      because each breast requires a different procedure. At the present time, because
      of the cost/benefit ratio of such procedures, they are reimbursed by health
      services. CONCLUSION: Although the results are not perfect, the psychological
      impact of such treatment is highly positive, suggesting that the requests of
      adolescent girls for this type of surgery may be encouraged.

PMID- 9538421
TI  - [Bacteriological study of purulent nasopharyngitis in children in Senegal].
AB  - BACKGROUND: S pneumoniae, H influenzae and M catarrhalis are the main bacteria
      isolated from rhinopharynx in Europe. The purpose of this work was to study the
      frequency of potential pathogenic bacteria isolated from acute purulent
      rhinopharyngitis among children in Senegal. POPULATION AND METHODS: Ninety-three
      children from one month to 7-years old suffering from purulent rhinopharyngitis
      were recruited from April 1 to July 1996. The withdrawal samples were taken from
      the cavum with a swab which was immediately immersed in an agar shipping medium.
      Bacteria's grouping and serotyping were made by immunoagglutination. A standard
      antibiogram was made for all isolates and furthermore the minimal inhibitory
      concentration (MIC) were determined for S pneumoniae. RESULTS: Two hundred
      bacterial strains were isolated: S pneumoniae 28% (60% of the children), C group
      streptococci: 19% (41% of the children), H influenzae: 15.5% (33% of the
      children), S pyogenes: 9.5% (20% of the children), S aureus: 8% (17% of the
      children) and M catarrhalis: 6% (13% of the children). The other isolates were: B
      and D groups streptococci, P aeruginosa and Klebsiella spp. S pnuemoniae strains
      belonged to serogroups 6, 19 and 23. Only three strains of H influenzae were
      capsulated (serotype b). Infants aged from 6 to 18 months were the most affected.
      No resistance to penicillin was observed for S pneumoniae and S pyogenes.
      Ampicillin (81%) and chloramphenicol (96%) both inhibited the majority of H
      influenzae strains. CONCLUSIONS: This descriptive bacterial epidemiology study of
      children's rhinopharynx's flora in Senegal allowed us to identify three major
      pathogenic germs: S pneumoniae, H influenzae and S pyogenes contributing to a
      better knowledge of these microorganisms' serotypes, biotypes and antibiotypes.

PMID- 9538422
TI  - [An unknown etiology of fetal ascites: acute intestinal intussusception].
AB  - BACKGROUND: Intussusception is a frequent diagnosis during the first year of
      life. However, it is an uncommon and very rare pathology in neonates and
      premature infants. CASE REPORTS: Two full term neonates presented an antenatal
      intussusception associated with fetal ascites; another premature infant developed
      an intussusception at the age of 15 days. In the three cases the diagnosis of
      intussusception had only been established during the laparotomy. A recent review
      of the literature revealed 13 cases of antenatal intussusception, one of these
      being associated with fetal ascites. CONCLUSION: The differential diagnosis of
      fetal ascites should always include intussusception. Early recognition of this
      pathology and prompt surgical action would avoid fatalities.

PMID- 9538423
TI  - [Juvenile hyaline fibromatosis].
AB  - BACKGROUND: Juvenile hyaline fibromatosis (JHF) is rare disease of autosomal
      recessive inheritance. CASE REPORT: A 14-year old boy, born to consanguineous
      parents was admitted because he suffered from multiple tumors since the age of 5
      years. These tumors were mobile, painful varying in size, located mainly on the
      head, the back, and extremities; they were associated with gingival overgrowth.
      Bone X-rays showed osteolytic lesions. The cognitive development was normal.
      Biopsy of tumors showed cords of spindle-shaped cells embedded in homogeneous
      eosinophilic matrix. The child was progressively disabled due to articular
      changes. Two of his brothers presented the same features. CONCLUSION: This new
      case of JHF confirms the severity of prognosis of such a fibromatosis presently
      considered as a hereditary disorder of collagen metabolism.

PMID- 9538424
TI  - [Postoperative mediastinitis due to methicillin resistant Staphylococcus
      epidermidis with low sensitivity to vancomycin].
AB  - BACKGROUND: Vancomycin is the drug of choice for methicillin-resistant
      Staphylococcus. Antibiotherapy failure is rarely clinically related to
      Staphylococcus with vancomycin low susceptibility. CASE REPORT: A surgical cure
      of an aortic stenosis in a neonate was complicated by a Staphylococcus
      mediastinitis. After initiation of antibiotherapy with vancomycin and rifampin
      and surgical debridement, there was a rapid improvement. Few days later, failure
      of therapy was obvious. Despite continuous infusion of vancomycin, with a serum
      level of 29 mg/L, blood cultures were positive again to Staphylococcus. There was
      no endocarditis or inadequate surgical drainage. Susceptibility of the
      Staphylococcus was tested, looking for a tolerant strain. The vancomycin minimum
      bactericidal concentration was 30 mg/L (above usual value 2 to 8 mg/L), while the
      minimum inhibitory concentration was 3.75 mg/L. A higher dosage of vancomycin
      associated with fusidic acid was rapidly efficient, and total recovery was
      achieved. CONCLUSION: In case of failure of vancomycin therapy, despite correct
      serum levels, the susceptibility of the Staphylococcus strain has to be
      determined. A low susceptibility strain prescribes more prolonged combination of
      two antibiotics.

PMID- 9538425
TI  - [Tuberculous pneumopathy in the course of cystic fibrosis].
AB  - BACKGROUND: Tuberculosis is rarely seen in patients with cystic fibrosis. CASE
      REPORT: A 14-year old female adolescent, regularly followed for a well-tolerated
      form of cystic fibrosis, developed an acute respiratory infection with
      consolidation of the left inferior lobe, and no response to the usual antibiotic
      treatment of cystic fibrosis. Mycobacterium tuberculosis was found in aspirate by
      fibroscopy, on Loewenstein medium. No familial or social infection contact were
      identified. Antituberculous chemotherapy with three drugs brought about a prompt
      improvement of sytemic signs, weight gain, resolution of pulmonary foci and
      sedation of biological findings referable to inflammation. CONCLUSION: This case
      report reminds us that tuberculosis may occur in cystic fibrosis patients.
      Loewenstein cultures should routinely be made when faced with an unexplainable
      worsening of the condition.

PMID- 9538426
TI  - [Transitory hyperinsulinism with hypoglycemia in asphyxia neonatorum].
AB  - BACKGROUND: Hypoglycemia is a well-known complication in neonates small for
      gestational age and in those with diabetic mothers. Birth asphyxiated infants can
      develop severe hypoglycemia due to reduced glycogen stores. CASE REPORTS: The
      first patient was born at 41 weeks, weighing 3,780 g by emergency cesarean
      section because of fetal distress. He developed a pneumothorax and hypoglycemia.
      He was given glucose infusion (at day 4: 20 mg/kg/d). Hyperinsulinism was
      confirmed: blood levels at 18.3 mU/L on day 1 and 11.7 mU/L on day 2. The
      infusion rate was gradually decreased. The second patient was born at 39 weeks,
      weighing 2,780 g by emergency cesarean section because of fetal distress. She
      needed glucose infusion (24 g/kg/d) because of hypoglycemia with hyperinsulinism
      (12.8 mU/L on day 2 and 11.7 mU/L on day 3). After 5 days, the infusion of
      glucose was replaced by oral feeding only. CONCLUSION: Transient hypoglycemia in
      asphyxiated newborn infants with hyperinsulinism must be considered even when
      hypoglycemia may be difficult to prove.

PMID- 9538427
TI  - [Pheochromocytoma: pediatric features].
AB  - Pheochromocytoma is a rare tumor in children which explains, together with its
      miscellaneous symptomatology, why the diagnosis may be delayed. The localization
      of the tumor(s) rests mainly on MIBG scintigraphy, and CT scan and/or magnetic
      resonance imaging. Thanks to a systematic preoperative treatment of hypertension
      and major progress in anesthesia, the operative mortality of pheochromocytomas in
      children is nowadays very low. Nevertheless two major problems remain: 1) the
      difficulty of diagnosing and treating the malignant forms, 2) the high frequency
      of recurrences, sometimes many years after the removal of the primary tumor. A
      regular long term supervision is therefore necessary after the surgical
      treatment.

PMID- 9538428
TI  - [The absence of style is the best style in medical writing].
AB  - The author describes his conception of medical writing. Based upon a critical
      analysis of articles recently published in the Archives de Pediatrie, he
      underlines the main principles which have to be respected for the writing of a
      medical article. This paper will be completed in an article entitled "The
      different redactional forms in medicine" to be published in the next issue
      (January 1988) of the journal.

PMID- 9538429
TI  - [Smith-Magenis syndrome].
AB  - Smith-Magenis syndrome is caused by a 17p11.2 deletion. It associates mental
      retardation, facial dysmorphism and brachydactyly; aberrant behavior and major
      sleep problems are present in 70% of the cases. It is probably under-diagnosed
      because the facial abnormalities are mild and the behavioral problems with
      hyperactivity and self-injuries are dominant, leading to the diagnosis of
      psychiatric pathology. However these behavioral problems are sufficiently
      characterized to allow the diagnosis of the syndrome and look for a 17p11.2
      microdeletion. Otorhinolaryngologic, ophthalmologic, cardiac and renal
      abnormalities can be associated and their evaluation is necessary. Smith-Magenis
      syndrome is considered as a contiguous gene syndrome. Genes have been mapped and
      isolated to the critical region, but their participation in the pathogenesis of
      the syndrome remains unclear.

PMID- 9538430
TI  - [Evaluation of the quality of life in pediatrics: how to collect the point of
      view of children].
AB  - There are very few available child quality of life questionnaires. We describe
      here a French questionnaire (AUQUEI) which consists of a structured format scale
      (26 items). The first part of the questionnaire studies child satisfaction.
      Response levels are measured by checking faces expressing different emotional
      states. The validation is satisfactory, and the questionnaire is able to
      differentiate healthy children from sick children (HIV positive). A second part
      of the questionnaire focuses on the child's own quality of life, and is based
      upon open-ended questions. This second approach allows to broaden the structured
      format scale and improves the understanding of the child's quality of life. It
      constitutes a necessary complement to the first part as it avoids using
      mechanically adult-specific concepts for children. We also found it to be
      sensitive enough to distinguish sick children from healthy ones. The AUQUEI
      questionnaire with its two complementary parts appears to be a potentially
      valuable tool to better understand the experience of sick children, in the
      various aspects of their life, and to follow their evolution.

PMID- 9538431
TI  - [Is it possible to improve sleep in children? A research on health education in
      nursery schools].
AB  - An educational project in nursery schools was carried out with the aim to improve
      children's sleep. Its effectiveness was tested in terms of awareness of families
      and length of sleep of children. The method was a prevention trial based on the
      random division of classes of 3-year old into two groups (intervention group and
      control group) comprising children enrolled in nursery schools in the Rhone
      region (France) in 1992. The project, lasting 2 years, relied on physicians from
      the community (Maternal, Child Health Service and School Health Service), their
      role being to mobilise the teaching teams, distribute specific teaching tools and
      raise awareness of families to respect the sleep patterns of children, during
      routine medical examinations. The study was carried out in 140 nursery schools
      with 1,500 children in each group. The evaluation was based on the application of
      a logistical regression model taking potentially confounding factors into
      account, and an analysis in sub-groups in order to demonstrate the effectiveness
      of intervention on particularly exposed groups. The results show: 1) the
      feasibility of such an intervention among nursery school children on a large
      scale, 2) the effectiveness of the action, with a reduction of the risk of "poor
      knowledge" among parents (OR = 0.76), particularly in urban areas, and a
      reduction in the risk "short nights" in the sub-group of children who had "
      little sleep at 3 years" in low social class families (OR = 0.50).

PMID- 9538432
TI  - [Contribution of vascular ultrasonic studies for the study of kidney diseases in
      children. Societe francophone de recherche en pediatrie].
AB  - The proximity of child's kidneys from the cutaneous surface allows a particularly
      sensitive exploration by doppler sonography, which in addition has the major
      advantage of being a non-invasive, non-irradiating and painless technique.
      However there are two limitations to this technique: the lack of cooperation of
      some children and the still limited availability of high quality equipment in
      intensive care units. Indeed most of the applications described in this paper
      (i.e., pyelonephritis, renovascular hypertension, tumors, acute renal
      insufficiency and renal vein thrombosis) require, besides an experienced
      operator, expensive power doppler equipment including high frequency and high
      resolution probes.

PMID- 9538433
TI  - [Radiological case of the month. Scoliosis revealing acute unilateral L5
      spondylolysis].

PMID- 9538434
TI  - [Hemolytic and uremic syndrome after measles, mumps and rubella vaccination.
      Fortuitous association?].

PMID- 9538435
TI  - [Splenic infarction revealing heterozygote sickle cell trait with spherocytosis].

PMID- 9538436
TI  - [Recurrent osteochondritis, desensitization therapy: a cause-effect
      relationship].

PMID- 9538437
TI  - [Atheism is spreading: the Olympian Gods rise in protest!].

PMID- 9538438
TI  - [Jejunal atresia and persistent mullerian duct syndrome].

PMID- 9538439
TI  - Molecular biology and the ENT surgeon in the millennium.

PMID- 9538440
TI  - Olfaction: a review.

PMID- 9538441
TI  - Otolaryngological treatments in hagiographical Byzantine texts (324-1453 A.D.):
      miracles or reality?
AB  - Hagiographical texts of the Byzantine period contain a significant number of
      miraculous treatments of several diseases of the ear, nose and throat. The
      comparison of the conservative treatments referred to as well as the often
      concealed surgical interventions of these texts with those known from the medical
      texts of the eminent Byzantine physicians, lead the writers to conclude that a
      series of real treatments were carried out in the churches or in the Xenones
      (hospitals) of Byzantium.

PMID- 9538442
TI  - Long-term observation after soft posterior meatal wall reconstruction in ears
      with cholesteatoma.
AB  - We performed tympanoplasty with reconstruction of the soft posterior meatal wall
      for the prevention of post-operative retraction pocket formation. Our method is
      characterized by the reconstruction of the soft posterior meatal wall, non
      obliteration with permanent or temporary materials, including Gelfoam, no use of
      a Palva flap and the use of fibrin glue for attaching the fascia to the posterior
      meatal skin. None of the patients experienced post-operative narrow-neck
      retraction pocket formation, and whenever aeration of the middle ear was
      disturbed, a balloon-like retraction was observed. Not all the posterior meatal
      walls retracted. The final position of the posterior meatal wall varied among the
      subjects. No serious cavity or hearing problems have occurred since surgery. Due
      to the strong possibility of post-operative retraction pocket formation in cases
      with a large balloon-like retraction, we rejected adopting the canal wall up
      technique or hard posterior meatal wall reconstruction.

PMID- 9538443
TI  - Endoscopic management of paranasal sinus mucocoeles.
AB  - Mucocoeles of the paranasal sinuses are relatively uncommon and in the past have
      been generally treated by an external surgical approach. Forty-eight mucocoeles
      in the frontal, fronto-ethmoidal and sphenoidal sinuses have been treated during
      the last five years, 20 by an entirely endonasal endoscopic approach and 28 by a
      combination of an external procedure and an endoscopic approach. There were no
      recurrences in the endoscopic group, with a mean follow-up of 34 months whilst
      three recurrences occurred in the combined external and endoscopic group which
      had a mean follow-up of 44 months. This may reflect the complexity and severity
      of concomitant disease. If a wide marsupialization can be achieved by an entirely
      endoscopic approach there are a number of advantages, notably a lack of facial
      scarring in children and young adults.

PMID- 9538444
TI  - Dissection tonsillectomy: pattern of post-operative pain, medication and
      resumption of normal activity.
AB  - A prospective study of 99 adults undergoing tonsillectomy was carried out to
      determine the pattern of post-operative pain, intake of medication and timing of
      return to work and normal swallowing. The differences in the pain scores, as
      measured by a visual analogue scale, between every third consecutive day
      following post-operative day four were found to be highly significant (p <
      0.001). Sixty-six patients (66.6 per cent) required medication in the form of
      analgesics and/or antibiotics after the first post-operative day. Sixty-four out
      of a total of 82 patients (78.2 per cent) returned to work within 14 days of
      surgery. Ninety-six patients (97 per cent) reported normal swallowing within 14
      days of surgery. These results suggest that the majority of adult patients
      undergoing tonsillectomy can be appropriately advised pre-operatively regarding
      the probable pattern and duration of post-operative pain and the timescales they
      can expect to return to work and normal swallowing.

PMID- 9538445
TI  - A clinical and videostroboscopic evaluation of laryngeal tuberculosis.
AB  - A series of 31 cases of tuberculous laryngitis is reviewed to assess the
      diagnostic features of the disease. The condition generally presents in males of
      late middle age who have pulmonary tuberculosis. It presents in a manner similar
      to laryngeal carcinoma except that painful dysphagia is a prominent symptom.
      Histological examination of biopsy material is usually the diagnostic procedure.
      Stroboscopy was able to document a number of abnormalities which included
      abnormalities of laryngeal configuration, vibratory asymmetry, reduction of
      amplitude and mucosal wave. Symptoms responded well to antituberculous
      chemotherapy.

PMID- 9538446
TI  - Hoarseness and gastroesophageal reflux in children.
AB  - The importance of a hoarse voice or voice change in children has not been
      stressed in the literature in the same way as it has been in adults. We present
      21 children who had been suffering from chronic hoarseness for more than three
      months and had on fibre-optic laryngoscopy findings suggestive of
      gastroesophageal reflux. None of them had complained of gastroesophageal
      symptoms. Twenty-four hour pH monitoring revealed that 13 (62 per cent) of these
      children had gastroesophageal reflux, seven (33 per cent) having gastroesophageal
      reflux more than three times the upper limit of normal. The pH graphs highlighted
      frequent refluxes, ranging from 0.4 to 37.4 refluxes per hour (median of 7.3
      refluxes/hour). The majority of these refluxes occurred when the child was awake
      as opposed to asleep, with a median of 14.8 refluxes/hour and 0.9 refluxes/hour
      respectively (p = 0.0009). The refluxes were classically of short duration. This
      study suggests that gastroesophageal reflux plays a direct role in the
      pathogenesis of chronic laryngitis and hoarseness in children.

PMID- 9538447
TI  - J incision in neck dissections.
AB  - Metastasis in the neck lymph system of primary tumours of the head and neck is
      frequently seen. In order to prevent this metastasis, neck dissection is carried
      out by various types of skin incisions. In this study, types of skin incision
      used in neck dissections were defined, and the advantages, disadvantages and
      results of J incisions, which have been performed on 320 radical neck dissection
      patients in our clinic between 1985-1996, were compared with those of other
      incision types.

PMID- 9538448
TI  - Melanotic neuroectodermal tumour of infancy arising in the maxilla.
AB  - Melanotic neuroectodermal tumour of infancy is an uncommon neoplasm that usually
      occurs in children aged one year or less. Difficulty in deciding the cellular
      origin of this tumour has led to numerous names, including congenital
      melanocarcinoma, melanotic epithelial odontoma, melanotic ameloblastoma, and
      retinal anlage tumour. Electron microscopy and histochemical studies, however,
      have now established the neural crest origin. The most frequent site of
      occurrence is the maxilla followed by the skull, the brain and the mandible. The
      genital organs are the most frequent extracranial site. We present two cases of
      melanotic neuroectodermal tumour of infancy arising in the maxilla.

PMID- 9538449
TI  - Cholesterol granuloma of the maxillary sinus: six cases from the same region.
AB  - It is common to find cholesterol granuloma in the mastoid antrum and air cells of
      the temporal bone, but it is very rare in paranasal sinuses. In the development
      of this pathology, the key factor is the presence of a closed cavity containing
      exudate and blood. Six cases of cholesterol granuloma of the maxillary sinus are
      presented from six years' study in our hospital. According to the main symptoms,
      clinical findings, and radiological appearance (except the destruction of the
      antrum wall in some patients), the pathology was similar to chronic maxillary
      sinusitis. All the patients were treated with radical operative techniques. In
      this study, we reviewed the literature and our cases, and could not detect any
      findings to explain why this pathology had occurred frequently in our district.
      We strongly recommend that investigations should be carried out on all specimens
      obtained from paranasal sinus surgery, because the cholesterol granuloma in the
      maxillary antrum could be mistaken for chronic sinusitis.

PMID- 9538450
TI  - Metastatic follicular thyroid carcinoma to the maxilla.
AB  - We present a unique case of metastatic follicular thyroid carcinoma to the hard
      palate and the maxillary sinus, a case that to our knowledge has not been
      reported before. Various malignant tumours that metastize to the maxilla are
      reviewed, and the therapeutic approach to follicular thyroid carcinoma metastasis
      to that area is also discussed. Follicular thyroid carcinoma should be included
      in the list of tumours that metastasize to the maxilla.

PMID- 9538451
TI  - Claudication on mastication following bilateral external carotid artery ligation
      for posterior epistaxis.
AB  - This case highlights a potentially disabling complication of intermittent
      claudication in the region of the masseter muscles on mastication, following
      bilateral external carotid artery ligation for epistaxis. Although there have
      been few reports of this complication this may be a reflection of the fact that
      the operation is rarely performed, and not because the complication is rare. Its
      potentially disabling nature, and its possible common occurrence after this
      procedure make awareness of it by surgeons who may carry out this procedure
      important.

PMID- 9538452
TI  - Chondrolipoma of the nasopharynx.
AB  - Lipoma is the commonest soft-tissue tumour arising anywhere in the body, but its
      occurrence in the nasopharynx is extremely rare. Only four cases in adults have
      been previously reported in the English literature. We describe a 63-year-old
      woman with a nasopharyngeal mass that was removed transorally and verified
      histopathologically as chondrolipoma, that is a lipoma with chondroid metaplasia.

PMID- 9538454
TI  - Laryngeal paralysis in organophosphorous poisoning.
AB  - Organophosphorous poisoning causing isolated laryngeal paralysis has only been
      rarely reported before. We describe a case of difficult extubation in a patient
      with organophosphorous poisoning, the cause of which was found to be bilateral
      vocal fold palsy. This is a type of intermediate paralysis that recovers with
      time. Such a condition should be thought of as a cause of dyspnoea or difficult
      extubation in patients with organophosphorous poisoning.

PMID- 9538455
TI  - Granular cell tumour of the larynx.
AB  - Granular cell tumour (GCT) of the larynx is an uncommon laryngeal tumour. It is
      always benign and commonly located in the posterior part of the larynx. Care must
      be taken to differentiate this lesion from others due to the presence of pseudo
      epitheliomatous hyperplasia which overlies the GCT and may occasionally mimic
      squamous cell carcinoma. Therefore, histological differentiation is important
      because these tumours are normally managed conservatively. The origin of this
      tumour is a matter of debate, but most authors believe it to be neural in origin.
      The rarity of this tumour in the male population prompted reporting this case in
      the literature.

PMID- 9538453
TI  - Primary non-Hodgkin's lymphoma of the larynx in an AIDS patient.
AB  - A case of primary non-Hodgkin's lymphoma of the larynx in an AIDS patient is
      presented with a review of the literature. Non-Hodgkin's lymphomas in AIDS
      patients are common but the primary laryngeal presentation is very rare. The
      symptoms usually include dysphonia and progressive airway obstruction requiring
      tracheostomy. As with laryngeal non-Hodgkin's laryngeal lymphomas in non-HIV
      positive patients the majority are of B cell lineage and respond well to
      radiotherapy. Our patient had a high grade lymphoma of B cell lineage which
      showed a good response to radiotherapy. The role of chemotherapy and surgery is
      not yet established. We suggest that the diagnosis of AIDS should not influence
      the management of these patients unless the individual is in the terminal disease
      stage.

PMID- 9538456
TI  - Primary lingual tuberculosis: a case report.
AB  - Tuberculosis is very common in India and Southeast Asia, where the prevalence
      rate is about four per 1000 population and the incidence rate of the disease is
      two per cent. Fifteen per cent of the tuberculous population of the world reside
      in India. Both secondary and primary tuberculous lesions of the tongue and oral
      cavity are rare. We report a 60-year-old male with the seventh case of primary
      lingual tuberculosis.

PMID- 9538457
TI  - Transverse sinus thrombosis and venous infarction of the brain following
      unilateral radical neck dissection.
AB  - Radical neck dissection is one of the commonest procedures performed in any unit
      dealing with head and neck surgery. Intracranial complications following this
      procedure are uncommon. Transverse sinus thrombosis and venous infarction of the
      brain following unilateral radical neck dissection have not been reported in the
      literature. We present a case in which this complication occurred following an
      uneventful radical neck dissection.

PMID- 9538458
TI  - Skull base osteitis following fungal sinusitis.
AB  - Aspergillus sp. sinusitis is not uncommon in immunocompromised patients but is
      unusual in patients who are not immunocompromised. The disease may occur as a
      saprophytic condition, as an allergic sinusitis or as a potentially lethal
      invasive disease. The differentiation between non-invasive and invasive
      Aspergillus sp. sinusitis is crucial and this distinction is fully discussed. The
      treatment options are also considered. Invasive disease requires aggressive
      treatment with long-term antifungal agents in sufficient doses combined with wide
      surgical excision. We present a patient who presented with invasive Aspergillus
      fumigatus sinusitis and subsequently developed cranial neuropathies and skull
      base osteitis. She was initially treated with oral itraconazole (400 mg daily)
      for 18 months but due to lack of response this was changed to a new experimental
      oral azole (voriconazole) which was continued for a further 14 months. She has
      since remained well for the last five years.

PMID- 9538459
TI  - Hodgkin's lymphoma of the nasopharynx.
AB  - The lymphoid tissues of Waldeyer's ring, including the nasopharynx, are very rare
      sites for Hodgkin's disease and are considered to be relatively resistant to it.
      This report of a case of Hodgkin's disease of the post-nasal space demonstrates
      the difficulty of making the diagnosis histologically and the characteristic
      immunohistochemical features of this disease. Before immunohistochemistry became
      so widely available, some authors speculated it might be underdiagnosed (Eavey
      and Goodman, 1982; O'Reilly and Kershaw, 1987). Judging by its continued rarity,
      this appears not to be the case.

PMID- 9538460
TI  - Metastasizing malignant oncocytoma of the submandibular gland.
AB  - Malignant oncocytomas are extremely rare tumours of the salivary glands. Fewer
      than 50 cases have been reported in the world literature so far, 34 of which were
      located in the parotid gland. Only three of these tumours have been located in
      the submandibular gland. We report one further case of a malignant oncocytoma of
      the submandibular gland in a 47-year-old man. Since a definite histological
      diagnosis of malignant oncocytoma can rarely be made both clinical and
      histopathological findings are essential in establishing the diagnosis. Treatment
      consists of wide surgical excision, neck dissection and post-operative
      radiotherapy. The prognosis with regard to five-year survival is poor because of
      metastatic disease.

PMID- 9538461
TI  - Antisense peptides: a critical mini-review.
AB  - Antisense peptides are defined as those generated from the non-coding strand of
      DNA, and represent a peptide analog to antisense RNA technologies. Peptides
      generated from both parallel and anti-parallel readings of the non-coding strand
      of DNA have displayed biological activity, although considerable controversy
      exists concerning the mechanism(s) by which these "anti-peptides" exert their
      effects. This paper provides a critical review of some of the key data and issues
      defining this emerging field and focuses on contradictions and discrepancies in
      the current studies. We also suggest some directions for future research such as
      more physico-chemical studies and the use of combinatorial chemistry techniques
      combined with solid phase binding studies to test, once and for all, the
      generality and specificity of antisense peptide interactions.

PMID- 9538462
TI  - Hematopoietic model with moving boundary condition and state dependent delay:
      applications in erythropoiesis.
AB  - An age-structured model for erythropoiesis is extended to include the active
      destruction of the oldest mature cells and possible control by apoptosis. The
      former condition, which is applicable to other population models where the
      predator satiates, becomes a constant flux boundary condition and results in a
      moving boundary condition. The method of characteristics reduces the age
      structured model to a system of threshold type differential delay equations.
      Under certain assumptions, this model can be reduced to a system of delay
      differential equations with a state dependent delay in an uncoupled differential
      equation for the moving boundary condition. Analysis of the characteristic
      equation for the linearized model demonstrates the existence of a Hopf
      bifurcation when the destruction rate of erythrocytes is modified. The parameters
      in the system are estimated from experimental data, and the model is simulated
      for a normal human subject following a loss of blood typical of a blood donation.
      Numerical studies for a rabbit with an induced auto-immune hemolytic anemia are
      performed and compared with experimental data.

PMID- 9538463
TI  - Evolution of transmission bias in cultural inheritance.
AB  - Evolution of transmission bias in cultural inheritance is investigated using
      simple models of cultural selection. Conventional models of cultural transmission
      describe cultural changes by incorporating transmission bias and non-vertical
      pathways into the ordinary population genetic framework. The methodology has been
      successful in understanding cultural changes in terms of natural selection, but
      it is difficult to see from the theoretical framework how biased transmission in
      favor of maladaptive traits might have evolved. To show that ordinary cultural
      processes lead at times to the evolution of a preference that favors a
      deleterious cultural variant, this study presents an alternative model of
      cultural transmission, where cultural elements are transmitted in a manner more
      like infections in epidemiological transmission. An ordinary equilibrium analysis
      indicates that, under certain conditions, runaway dynamics emerges and the
      coevolution of a maladaptive cultural variant and an associated preference in
      favor of the maladaptive variant is observed. If the preference of an individual
      does not change during its ontogeny (e.g., if it is transmitted genetically),
      however, then cultural selection alone does not produce such runaway dynamics,
      and only those preferences that favor adaptive variants should eventually evolve.
      Since cultural processes may at times result in a reduction in the fitness of
      individuals, simplistic adaptive interpretations of culture are unconvincing
      without detailed specification of the cultural processes involved. Moreover,
      cultural runaway of this kind may help to explain the existence of traits that
      are apparently maladaptive at the individual level but may be advantageous for
      the group. Inferences are also made regarding the observed differences between
      human and non-human social information transfer.

PMID- 9538464
TI  - On the role of a possible dialogue between cytokine and TCR-presentation
      mechanisms in the regulation of autoimmune disease.
AB  - Autoimmune diseases are thought to occur through some weakness in an active
      process of autoregulation. Two different regulatory mechanisms have been proposed
      separately during the years: a "non-specific" mechanism, via Th1-Th2 non-specific
      cytokines, and a "specific" one-on-one mechanism, via presentation of peptides,
      i.e., T cell receptor (TCR) peptides, by the T cells themselves. Several anti
      idiotypic models rely on the latter to explain the effects of "T-cell
      vaccination" therapy. We present and analyse a model for the interaction between
      both regulatory mechanisms within an ensemble composed of Th1 and Th2 cells. Our
      model shows how both TCR presentation and non-specific Th1/2 signals can
      cooperate in the choice of the prevailing Th1 or Th2 response. We show how TCR
      presentation can foster regulation, without necessitating a particular
      "suppressor" agent, of the type that some have assumed to play a central role in
      the regulation of autoimmunity. Our results suggest an important role for the
      cells' sensitivities to Th1 and Th2 derived cytokines; only for certain
      sensitivity ranges, is it possible to switch dominance between subtypes. It is
      argued that memory is sustained via modulation of sensitivities to cytokines, not
      only to antigens. The results and hypotheses also suggest one possible reason for
      the known correlation between standard and autoimmune diseases. Several therapies
      and informative experiments are suggested. We argue, for example, that
      administering a non-relevant peptide while increasing the ratio between the
      clones reactive to it and other clones in the pancreas, might cure autoimmune
      diabetes. Moreover, we predict that disease could be prevented by administering
      an autoimmune peptide at an early age while forcing the system to react in a Th2
      fashion.

PMID- 9538465
TI  - [Paris-Trousseau thrombocytopenia: a new entity and a model for understanding
      megakaryocytopoiesis].

PMID- 9538466
TI  - Human platelet antigen frequencies of platelet donors in the French population
      determined by polymerase chain reaction with sequence-specific primers.
AB  - To prevent human platelet alloimmunization, Blood Transfusion Centres have to
      develop a strategy close to the erythrocytes' one. The first step of this
      strategy is to perform the HPA typing of donors with an accurate method. We
      applied the PCR-SSP to type 800 platelet donors in the HPA-1 and HPA-5 systems
      and 350 in the HPA-2 and HPA-3 ones. This study reports the human platelet
      antigen frequencies of four platelet-specific alloantigen systems in the French
      population. The results are quite similar to those currently published for
      Caucasian population frequencies. Low prevalences are observed for the HPA-1b,
      (2%), HPA-2b (0.6%) and HPA-5b (2%) groups. Furthermore, this study confirms the
      need to type donors and recipients in the HPA-1 system at least, in case of post
      transfusion pupura and platelet refractoriness to platelet transfusion therapy.

PMID- 9538467
TI  - [Seroprevalence of HBV, HCV and HDV hepatitis markers in 500 patients infected
      with the human immunodeficiency virus].
AB  - The serological status for both hepatitis B, C and D viruses was analyzed for 500
      HIV seropositive patients and for 1037 of a control group. The prevalence was
      31.4% for anti HCV, 13.8% for HBs Ag and 69.0% for one or more HBV markers in HIV
      positive patients and respectively 2.5%, 2.7% and 13.1% in control group. The
      markers for hepatitis D were founded among 21% of the HBs Ag carriers (patients
      and control group), correlated with drug i.v. use. The prevalence of anti-HCV was
      71.6% in subjects who had blood-borne HIV infection and 1.5% in those with
      sexually acquired infection. The prevalence in control group was 10.2% and 1.7%
      respectively according to the same risk factors. The prevalence of HBs Ag was
      higher among HIV positive patients with sexual risk (17.5%) than with blood
      exposition (9.9%) and a variation in the same direction is observed in control
      group (3% v.s. 1%). The relation between markers for hepatitis B and hepatitis C
      was negative.

PMID- 9538468
TI  - [Value of proctosigmoidoscopy with bacteriological culture of colonic biopsies in
      the etiological diagnosis of post-antibiotic acute diarrhea in adults.
      Prospective study in 24 patients].
AB  - The aim of this study was to analyse the interest of proctosigmoidoscopy and
      biopsies microbiology in antibiotic-associated acute diarrhea in adults. Between
      February 1993 and October 1995, we have studied prospectively 24 patients with
      antibiotic-associated acute diarrhea. Ages ranged from 17 to 83 years. They had
      taken antibiotics: amoxicillin (n = 8) amoxicillin-clavulanic acid (n = 11),
      cephalosporinia (n = 3), cotrimoxazole (n = 1), macrolide (n = 1). For each
      patient, 2 stool cultures with Cytotoxin assay for Clostridium difficile and 3
      fecal samples for parasitic enteropathogens were collected. Proctosigmoidoscopy
      with biopsies microbiology was carried out in all patients. Stool culture was
      always negative but colonic biopsies cultures were positive with Klebsiella
      oxytoca in 7 patients. Cytotoxin assay of C. difficile was positive in 11
      patients. Proctosigmoidoscopy permitted also diagnosis of 2 pseudomembranous
      colitis without cytotoxin assay of C. difficile. Proctosigmoidoscopy permitted
      diagnosis of 83% of antibiotic-associated acute diarrhea. Complementary to
      Cytotoxin assay of C. difficile, it should be necessary in antibiotic-associated
      acute diarrhea in adults.

PMID- 9538469
TI  - Prevalence and sensitivity to antibiotics of Enterobacteriaceae isolated from
      urinary cultures in some microbiology laboratories of a city in west Greece.
AB  - The prevalence of Enterobacteriaceae from midstream urine samples from patients
      with community acquired urinary tract infections (UTI) of a town in SW Greece
      during one year period and their susceptibility to antibiotics were studied. The
      most frequently recovered pathogens were E. coli (77%), Proteus mirabilis (10%),
      Klebsiella spp (8.7%), Enterobacter spp (2.5%) and Citrobacter freundii (1.8%).
      E. coli were found more resistant to carbenicillin, the combination of
      amoxicillin/clavulanic acid and cotrimoxazole. Half of the strains were found
      resistant to more than one antibiotics. All strains were found sensitive to
      aminoglucosides, 2nd generation cephalosporines (except cefoxitin), 3rd
      generation cephalosporines, aztreonam and imipeneme. According to our results a
      statistically significant increase of the resistance to antibiotics at
      individuals over 45 years of age was noticed. The positivity of the samples was
      not correlated to prior antibiotic consumption and to the occupation of the
      participants or their residence.

PMID- 9538470
TI  - [Application from chemiluminescence to serological diagnosis of human
      toxoplasmosis].
AB  - Diagnostic Products Corporation has chosen chemiluminescent for the new kit of
      quantitative measurement of IgG and qualitative detection of IgM antibodies to
      Toxoplasma gondii, 878 human sera of principal diagnosis situations were tested,
      and the results obtained with the IMMULITE Toxoplasmosis kit were compared with
      those of the Parasitology and Mycology Laboratory of the University of Lille.
      Chemiluminescent allows a sensitive and specific determination of immunity. In
      the same ways, this method is able to detect earlier specific IgM and IgG during
      seroconversion. The kit of quantitative measurement of IgG and qualitative
      detection of IgM is reproducible and sensitive; this confirms the interest for
      the pediatric diagnosis of congenital toxoplasmosis.

PMID- 9538471
TI  - Epidemiological survey of Neisseria meningitidis susceptibility to penicillin G
      in France.
AB  - The susceptibility of 82 strains of Neisseria meningitidis to penicillin G and
      amoxicillin was evaluated with two media "gonococci-meningococci" medium (G
      medium) derived from Mueller Hinton and chocolate agar. Among these 82 strains 52
      were isolated from CSF and/or blood and 30 from miscellaneous isolates. G medium
      was compared with chocolate agar using the correlation between diameters and MIC
      and the E-test. Routinely standardised antibiogram is still used but the authors
      added the following techniques 1) MIC of penicillin G is tested (0.06; 0.125;
      0.250; 0.50 mg/l); 2) use of oxacillin disc charged with 5 micrograms.
      Penicillinase producing meningococci were not found. Standardised antibiogram on
      4192 strains resulted in a modal distribution of diameters between 18 to 40 mm.
      Moderate meningococci susceptible strains to penicillin G are increasing in
      France: 1994: 4%; 1995: 11%; 1996: 18%.

PMID- 9538472
TI  - Kinetics of chlorhexidine on intact skin following a single application.
AB  - Residual chlorhexidine concentrations were measured after application of a single
      dose on the skin of 22 healthy volunteers. Dosage by high-pressure liquid
      chromatography in the skin cleansers revealed that the residual concentrations
      were higher than chlorhexidine MICs for most organisms of the resident skin flora
      and some responsible for hand-borne infections, even 24 h after application.

PMID- 9538473
TI  - [Traceability of drugs derived from blood: regulation and pharmaco-economic
      implications after 24 months of application in Paris CHU].
AB  - Since January 1, 1995, the supply, stockage, dispensing and traceability of Blood
      Derivative Medicinal Products (BDMP) are subject to pharmaceutical regulations. A
      review of 24 months' application at Necker-Enfants Malades Hospital is presented
      and analysed. A distinction is drawn between two categories of BDMP: 1) anti
      hemophilia BDMP, factors of plasma or recombinant origin; 2) non-anti-hemophilia
      BDMP, covering albumin, immunoglobulins (Ig), biological glues and other clotting
      factors. BDMP are subject to a hospital traceability procedure. In this respect,
      we have constructed a tryptic nominative model prescription, though dotations are
      granted for only certain prescription sectors (operating room, ICU) and certain
      products (biological glues, albumins). A dispensing-administration form is
      invariably attached to each bottle. Between January 1, 1995 and December 31,
      1996, 8225 dispensing procedures for BDMP were recorded, with a total cost of
      52,931,586 francs (i.e. 69% anti-hemophilia products v.s. 31% non-antihemophilia
      products). The Factor VIII market is divided more or less equally between factors
      of human and recombinant origin. The risk of viral transmission is considered to
      be virtually nil with recombinant products, despite their being stabilized by
      human albumin. The traceability rate of anti-hemophilia factors was 100%. Albumin
      consumption was 182,106 g at a cost of 3,358,250 francs. The following
      indications were adopted at a Local Medicines Committee: 1) in adults:
      hypoalbuminemia associated with edema or ascites; 2) in children: digestive
      disorders leading secondarily to exsudative enteropathy and/or hypoalbuminemia.
      Consumption of polyvalent Ig was 69,213 g, i.e. 10,856,722 francs. These products
      were prescribed in accordance with the directives of the Committee for Evaluation
      and Distribution of Technological Innovations. Consumption of specific Ig and
      biological glues may seem modest in relation to that of other products. BDMP
      expenditure appears particularly heavy here (about 26.5 MF/year) but consensual
      adoption of therapeutic guidelines has enabled rationalization of prescribing
      conditions with the best possible consideration of benefit/risk vs costs ratios.
      Traceability and drug safety monitoring procedures are linked to and integrated
      in the more global concept of Quality Assurance. Since January 1995, several
      withdrawals of batches have been recorded because of suspicion (or death due to)
      Creutzfeld-Jakob, or post-donation HIV seroconversion. In this area, the Hospital
      Pharmacist acts by the establishment in real time of a permanent safety link
      between the patient, a prescriber, an indication, a product prescribed and the
      product actually administered.

PMID- 9538474
TI  - [Non-antibiotic effects of antibiotics: from side effects to therapeutic uses].
AB  - Sometimes therapeutic needs to tap drugs side effects of a treatment to show new
      indications for those drugs. Antibiotics, which are somewhat some often-used
      drugs, are frequently prescribed in non-infectious pathologies. Some indications
      are reported in the literature: immunosuppressive or antiinflammatory (disulone,
      salazopyrine, cotrimoxazole, clofazimine, fusidique acid), small bowel prokinetic
      action (macrolides), endocrine effects (demeclocycline, ketoconazole), enzymatic
      effects (rifampicine, cyclines), sclerotherapy (cyclines), pro- or anti-tumoral
      effects. This incomplete list is growing up every days.

PMID- 9538475
TI  - [Current data on metalloproteinases, obligatory partners of tumor progression].
AB  - Metastasis is a complex process that requires sequential interactions between the
      invasive cell and the extracellular matrix. These interactions are characterized
      by cell adhesion and migration. Cell adhesion involves specific receptors.
      Migration requires the induction and secretion of proteolytic enzymes belonging
      to the matrix metalloproteinases (MMP) family. In most cancers, stromal cells
      secrete collagenases or gelatinases under the influence of cancer cells. The MMPs
      are secreted as inactive forms. In order to cross basement membrane and then to
      reach the extracellular matrix, the MMPs undergo an activation step which
      involves plasmin, growth factors or membrane-type matrix metalloproteinases (MT
      MMPs). The molecular mechanisms involves protein-kinase C activation. MMPs are
      associated with tissue inhibitors of metalloproteinases (TIMPs) with which they
      form high affinity non covalent 1:1 complexes. Upregulation of MMPs or down
      regulation of TIMPs lead to an imbalance of this ratio which favours invasive
      process. Consequently, the development of matrix metalloproteinase inhibitors
      such as Batimastat may provide interesting tools for cancer therapy.

PMID- 9538476
TI  - [Contribution of dual CD13/CD14 markers in combination with CD34 for the
      collection of peripheral hematopoietic stem cells].
AB  - We evaluated the reliability of a flow cytometry technique for counting
      mononuclear cells (MNCs) in cytapheresis products. Eighty freshly-prepared
      samples of peripheral stem cells were studied using a dual immunolabeling
      technique with antibodies to CD13/CD14, and were also labeled with anti-CD34.
      Results of this immunophenotype determination were compared to those of the
      conventional method for counting MNCs under the microscope. Dual CD13/CD14
      labeling was found to be a simple and reliable method for counting MNCs in the
      presence of immature and stimulated cells. When used in combination with CD34
      labeling, the dual immunolabeling method helped improve the evaluation of the
      quality of peripheral stem cell grafts.

PMID- 9538477
TI  - [Sensitivity of Pseudomonas aeruginosa to amikacin and to isepamicin in surgery
      and in intensive care].
AB  - To evaluate the respective interest of amikacin and isepamicin in P. aeruginosa
      infection, the resistance level was ascertained using the disk method.
      Susceptibility was also tested for gentamicin, tobramycin and netilmicin.
      Isolates came from three surgical units and from two intensive care units.
      Serotyping was proceeded, and isolates coming from the same patient, with the
      same susceptibility pattern and the same serotype was included once only: 197
      strains were thus obtained. Resistance level was 22.3% for amikacin, and 28.4%
      for isepamicin. Discrepancies were found in 14.7% of cases (major: 8.1%; minor:
      6.6%). Discordant strains were more susceptible to amikacin than to isepamicin in
      30/37 cases, and more susceptible to isepamicin in 7/37 cases. This difference
      was highly significant (paired Chi-2 test: p < 10(-4). The best susceptibility to
      amikacin was found in all serotypes and units.

PMID- 9538478
TI  - Assessment of disease activity in systemic vasculitis.
AB  - The systemic vasculitides are a group of inflammatory disorders characterised by
      relapses and remission. Before the introduction of immunosuppressive drugs,
      mortality was unacceptably high. Immunosuppressive therapy has had a therapeutic
      impact, but at the cost of increased risk of infection and other adverse effects.
      Differentiating infection from active disease can be difficult, and the
      inappropriate prescription of immunosuppressive drugs can be fatal. Hence disease
      indices which can aid physicians to identify the active phase of disease and
      enable early treatment, will be valuable in the management of this group of
      disorders.

PMID- 9538479
TI  - Angioplasty and stenting in the carotid and vertebral arteries.
AB  - Carotid and vertebral artery percutaneous transluminal angioplasty and stenting
      are new, experimental techniques. Their potential uses are discussed and the
      results and complications reported to date are reviewed.

PMID- 9538480
TI  - Malignant hyperthermia.
AB  - Malignant hyperthermia is a rare autosomal dominant trait that predisposes
      affected individuals to great danger when exposed to certain anaesthetic
      triggering agents (such as potent volatile anaesthetics and succinylcholine). A
      sudden hypermetabolic reaction in skeletal muscle leading to hyperthermia and
      massive rhabdomyolysis can occur. The ultimate treatment is dantrolene sodium a
      nonspecific muscle relaxant. Certain precautions should be taken before
      anaesthesia of patients known to be susceptible to malignant hyperthermia. These
      include the prohibition of the use of triggering agents, monitoring of central
      body temperature and expired CO2, and immediate availability of dantrolene. In
      addition, careful cleansing of the anaesthesia machine of vapours of halogenated
      agents is recommended. If these measures are taken, the chances of an MH episode
      are greatly reduced. When malignant hyperthermia-does occur in the operating
      room, prompt recognition and treatment usually prevent a potentially fatal
      outcome. The most reliable test to establish susceptibility to malignant
      hyperthermia is currently the in vitro caffeine-halothane contracture test. It is
      hoped that in the future a genetic test will be available.

PMID- 9538481
TI  - Recent developments in assessing medical students.
AB  - Most medical schools in the UK are revising their undergraduate courses in
      response to the recommendations published by the General Medical Council
      Education Committee in Tomorrow's doctors. However, achievement of the objectives
      of curricular change is attendant on revision of the assessment process. This
      paper reviews traditional and more recently developed methods for assessment of
      medical education in the light of the General Medical Council's recommendations
      which relate specifically to summative assessment of the core curriculum. The
      importance of reliability and validity is highlighted, and the case for criterion
      referenced assessment is examined.

PMID- 9538482
TI  - An obstetrics and gynaecology graduate residency programme in Venezuela.
AB  - We present our experience on the design and development of a gynaecology and
      obstetrics graduate residency programme, developed in the Department of
      Obstetrics and Gynecology at the Dr Adolfo Prince Lara Hospital, Puerto Cabello,
      Venezuela, in which medical specialists and residents participate
      synergistically. From January to September 1993, curricular activities were
      planned and students selected. The programme started in October 1993, with six
      residents for a three-year programme. Courses were given by medical specialists
      from the Department. In addition to a Programme Coordinator, there is also a
      Residents' Coordinator, appointed for a two-month term of office; specific
      functions were assigned for residents occupying this position. All the programmed
      activities for three years were accomplished, including lectures and rotations,
      with an important record of surgical interventions. In our grade system,
      residents got an average of 18 over a maximum of 20 points. Residents also
      participated as speakers in workshops, special courses and national medicinal
      meetings, in which they presented a total of nine papers. Activities were
      evaluated bimonthly in meetings with students and each semester by the Graduate
      Committee. The first class graduated in September 1996. Results suggest that
      resident participation in graduate programmes is an important part of their
      education.

PMID- 9538483
TI  - An audit of prostate-specific antigen and clinical symptoms in general practice.
AB  - The objective was to devise local guidelines for the referral of patients with
      suspected prostatic carcinoma following evaluation by a retrospective audit of
      the value of the prostate-specific antigen concentration, together with age,
      urological symptoms, and digital rectal examination in the diagnosis of carcinoma
      of the prostate. Relevant details were collected from the notes of 582 patients
      from general practice and hospital. The significant diagnostic factors were
      ascertained by stepwise logistic regression. Prostate-specific antigen
      concentration, digital rectal examination and significant terminal dribbling were
      the most powerful factors in the diagnosis of carcinoma of the prostate. When
      prostate-specific antigen concentration was considered in isolation, a value of
      6.5 ng/ml appeared appropriate for referral. Age was not significant, perhaps due
      to the narrow patient age range. The significant diagnostic factors were built
      into an algorithm calculating the probability of carcinoma of the prostate. This
      algorithm, together with prostate-specific antigen concentration results and
      digital rectal examination findings, forms the basis of the referral guidelines
      and a subsequent prospective study.

PMID- 9538484
TI  - How to pass the MRCP (UK) examination--ask a successful candidate!
AB  - Recently successful MRCP (UK) candidates were asked to rate the value of clinical
      experience, reading, practice with past or simulated examination papers and
      commercially organised courses as preparation for parts 1 and 2 of the
      examination. With respect to part 1, practice with past and simulated papers was
      unanimously felt to be of crucial importance with examination-focused reading
      helpful. Clinical experience was deemed irrelevant and commercially organised
      courses a matter of individual choice. For part 2, clinical experience was felt
      to be of fundamental importance but needed to be practised in an 'examination
      atmosphere'. Both general reading and practice with past and simulated papers
      were judged helpful and commercially organised courses were perceived to be of
      more value than for part 1. Trainees should be advised to seek advice on
      examination preparation from both 'authoritative sources' and their recently
      successful colleagues.

PMID- 9538485
TI  - Imported infections in east Birmingham children.
AB  - This 15-month prospective study of admissions to a children's ward found imported
      infections in 58 children (1.3% of admissions), aged between two months and 15
      years. Most had visited the Indian subcontinent 14 (1-341) days earlier. Few had
      taken preventative measures. The commonest infection was malaria (n = 23).

PMID- 9538486
TI  - Images in clinical medicine. Stab wounds to the heart: a useful radiological
      sign.

PMID- 9538487
TI  - Hyperosmolar nonketotic coma precipitated by lithium-induced nephrogenic diabetes
      insipidus.
AB  - A 45-year-old man, with a 10-year history of manic depression treated with
      lithium, was admitted with hyperosmolar, nonketotic coma. He gave a five-year
      history of polyuria and polydipsia, during which time urinalysis had been
      negative for glucose. After recovery from hyperglycaemia, he remained polyuric
      despite normal blood glucose concentrations; water deprivation testing indicated
      nephrogenic diabetes insipidus, likely to be lithium-induced. We hypothesize that
      when this man developed type 2 diabetes, chronic polyuria due to nephrogenic
      diabetes insipidus was sufficient to precipitate hyperosmolar dehydration.

PMID- 9538488
TI  - Coexistence of hereditary angioedema and Turner's syndrome.
AB  - A 34-year-old woman presented to the out-patient clinic with angioedema and type
      II hereditary angioedema was confirmed immunologically. She also volunteered she
      had never had a menstrual period and physical examination identified several
      features of Turner's syndrome. A mosaic karyotype with XY and XO was found on
      chromosomal analysis and gonadectomy was performed in view of the high risk of
      gonadoblastoma. After commencing oestrogen at physiological replacement doses,
      the patient experienced a marked deterioration in both the severity and frequency
      of angioedema attacks. Coexistence of hereditary angioedema and Turner's syndrome
      has not previously been reported and this case highlights the detrimental C1
      inhibitor level lowering effect of oestrogen in hereditary angioedema.

PMID- 9538489
TI  - Isolated angiitis of central nervous system with pleocytosis in the cerebrospinal
      fluid.
AB  - We report the case of a 32-year-old woman with isolated angiitis of the central
      nervous system. This case shows that high levels of pleocytosis may not rule out
      isolated angiitis of the central nervous system if this diagnosis can be
      considered on clinical grounds.

PMID- 9538490
TI  - Anabolic steroid induced hypogonadism treated with human chorionic gonadotropin.
AB  - A case is presented of a young competitive body-builder who abused anabolic
      steroid drugs and developed profound symptomatic hypogonadotrophic hypogonadism.
      With the help of prescribed testosterone (Sustanon) he stopped taking anabolic
      drugs, and later stopped Sustanon also. Hypogonadism returned, but was
      successfully treated with weekly injections of human chorionic gonadotropin for
      three months. Testicular function remained normal thereafter on no treatment. The
      use of human chorionic gonadotropin should be considered in prolonged
      hypogonadotrophic hypogonadism due to anabolic steroid abuse.

PMID- 9538491
TI  - Visual problems following dural puncture.

PMID- 9538492
TI  - Seizure, mental retardation and abnormal cranial CT in a child.

PMID- 9538493
TI  - A man with purple toes.

PMID- 9538494
TI  - Blunt abdominal trauma.

PMID- 9538495
TI  - A case of a yellow patient.

PMID- 9538496
TI  - A rare cause of crepitus.

PMID- 9538497
TI  - Severe cholestatic hepatitis following cloxacillin treatment.

PMID- 9538498
TI  - Highlights from the Fifth International Conference on Travel Medicine held in
      Geneva, Switzerland, on 24-27 March 1997.

PMID- 9538499
TI  - False-positive serum LDH level due to interference from immunoglobulin.

PMID- 9538500
TI  - Delays to thrombolysis.

PMID- 9538501
TI  - Arterial re-bleed following tPA administration.

PMID- 9538502
TI  - Cell volume and gene expression.

PMID- 9538503
TI  - Relationships between Na+/glucose cotransporter (SGLT1) currents and fluxes.
AB  - The relationships between currents generated by the rabbit Na+/glucose
      cotransporter (SGLT1) and the fluxes of Na+ and sugar were investigated using
      Xenopus laevis oocytes expressing SGLT1. In individual voltage-clamped oocytes we
      measured: (i) the current evoked by 10 mM alpha MG and the 22Na+ uptake at 10 mM
      Na+; (ii) the currents evoked by 50 to 500 microM [14C]alpha MG and the
      [14C]alpha MG uptakes at 100 mM Na+; and (iii) phlorizin-sensitive leak currents
      in the absence of sugar and 22Na+ uptakes at 10 mM Na+. We demonstrate that the
      SGLT1 leak currents are Na+ currents, and that the sugar-evoked currents are
      directly proportional to both alpha MG and Na+ uptakes. The Na+/alpha MG coupling
      coefficients were estimated to be 1.6 at -70 mV and 1.9 at -110 mV. This suggests
      that the rabbit SGLT1 Na+/alpha MG stoichiometry for sugar uptake is 2 under
      fully saturating, zero-trans conditions. Coupling coefficients of less than 2 are
      expected under nonsaturating conditions due to uncoupled Na+ fluxes (slippage).
      The similarity between the Na+ Hill coefficients and the coupling coefficients
      suggests strong cooperativity between the two Na+ binding sites.

PMID- 9538504
TI  - Environmental KCl causes an upregulation of apical membrane maxi K and ENaC
      channels in everted Ambystoma collecting tubule.
AB  - Patch clamp methods were used to characterize the channels on the apical membrane
      of initial collecting ducts from Ambystoma tigrinum. Apical membranes were
      exposed by everting and perfusing fragments of the renal tubule in vitro. Tubules
      were dissected from two groups of animals; one maintained in tap water, and the
      other kept in a solution of 50 mM KCl from seven to nineteen days. Patches of
      apical membranes on tubules taken from animals exposed to tap water expressed low
      conductance amiloride sensitive sodium channels (ENaC) in 22 of 49 patches. Only
      three maxi K channels were observed in this group. In animals exposed to KCl, low
      conductance amiloride sensitive sodium channels, 3.7 +/- 0.2 pS (36 of 45
      patches) and high-conductance 98.3 +/- 5.0 pS (19 of 45 patches) potassium
      channels were observed. The estimated density of apical maxi K channels increased
      dramatically from 0.08 to 0.76 channels/mu 2 in tubules taken from animals
      exposed to KCl. All but four of nineteen patches which contained maxi K channels
      also expressed the low conductance sodium channels. Therefore, at least 85% of
      the maxi K channels studied were in principal cells. We speculate that the
      increase in maxi K channel activity may represent a mechanism for enhancing the
      potassium secretory capacity of the initial collecting duct. As expected,
      exposure of the animals to 50 mM KCl prior to dissection of the initial
      collecting ducts also increased the estimated density of ENaC from 0.99 to 3.89
      channels/mu 2. This upregulation of sodium channel activity is presumably related
      to the widely recognized effect of potassium loading to increase the plasma
      aldosterone level.

PMID- 9538505
TI  - Conformational analysis of amphotericin B--cholesterol channel complex.
AB  - A molecular model of ionic channel formed by flexible molecules of amphotericin B
      and cholesterol is proposed. Complexes with axial symmetry from 5 to 11 were
      simulated. In contrast to the model of the channel formed from rigid molecules,
      flexible molecules form a tightly packed structure consolidated by both
      dispersive forces and intermolecular hydrogen bonds. Contributions of a lactone
      ring, polar heads, cholesterol and lipid environments to the global energy of the
      complex formation are discussed. Among the complexes capable of ionic transport,
      that of axial symmetry eight is preferable. Two types of complexes, differing by
      the number of intramolecular hydrogen bonds, are shown to be possible.

PMID- 9538506
TI  - Molecular mechanisms of polymyxin B-membrane interactions: direct correlation
      between surface charge density and self-promoted transport.
AB  - We have studied the interaction of the polycationic peptide antibiotic polymyxin
      B (PMB) with asymmetric planar bilayer membranes via electrical measurements. The
      bilayers were of different compositions, including those of the lipid matrices of
      the outer membranes of various species of Gram-negative bacteria. One leaflet,
      representing the bacterial inner leaflet, consisted of a phospholipid mixture
      (PL; phosphatidylethanolamine, -glycerol, and diphosphatidylglycerol in a molar
      ratio of 81:17:2). The other (outer) leaflet consisted either of
      lipopolysaccharide (LPS) from deep rough mutants of PMB-sensitive (Escherichia
      coli F515) or -resistant strains (Proteus mirabilis R45), glycosphingolipid (GSL
      1) from Sphingomonas paucimobilis IAM 12576, or phospholipids
      (phosphatidylglycerol, diphytanoyl-phosphatidylcholine). In all membrane systems,
      the addition of PMB to the outer leaflet led to the induction of current
      fluctuations due to transient membrane lesions. The minimal PMB concentration
      required for the induction of the lesions and their size correlated with the
      charge of the lipid molecules. In the membrane system resembling the lipid matrix
      of a PMB-sensitive strain (F515 LPS/PL), the diameters of the lesions were large
      enough (d = 2.4 nm +/- 8%) to allow PMB molecules to permeate (self-promoted
      transport), but in all other systems they were too small. A comparison of these
      phenomena with membrane effects induced by detergents
      (dodecyltriphenylphosphonium bromide, dodecyltrimethylammonium bromide,
      sodiumdodecylsulfate) revealed a detergent-like mechanism of the PMB-membrane
      interaction.

PMID- 9538507
TI  - Characteristics of a low affinity passive Ca2+ influx component in rat parotid
      gland basolateral plasma membrane vesicles.
AB  - We have previously reported the presence of two Ca2+ influx components with
      relatively high (KCa = 152 +/- 79 microM) and low (KCa = 2.4 +/- 0.9 mM)
      affinities for Ca2+ in internal Ca2+ pool-depleted rat parotid acinar cells
      [Chauthaiwale et al. (1996) Pfluegers Arch. 432: 105-111]. We have also reported
      the presence of a high affinity Ca2+ influx component with KCa = 279 +/- 43
      microM in rat parotid gland basolateral plasma membrane vesicles (BLMV).
      [Lockwich, Kim & Ambudkar (1994) J. Membrane Biol. 141:289-296]. The present
      studies show that a low affinity Ca2+ influx component is also present in BLMV
      with KCa = 2.3 +/- 0.41 mM (Vmax = 16.36 +/- 4.11 nmoles of Ca2+/mg protein/min).
      Our data demonstrate that this low affinity component is similar to the low
      affinity Ca2+ influx component that is activated by internal Ca2+ store depletion
      in dispersed parotid gland acini by the following criteria: (i) similar KCa for
      calcium flux, (ii) similar IC50 for inhibition by Ni2+ and Zn2+; (iii) increase
      in KCa at high external K+, (iv) similar effects of external pH. The high
      affinity Ca2+ influx in cells is different from the low affinity Ca2+ influx
      component cells in its sensitivity to pH, KCl, Zn2+ and Ni2+. The low and high
      affinity Ca2+ influx components in BLMV can also be distinguished from each other
      based on the effects of Zn2+, Ni2+, KCl, and dicyclohexylcarbodiimide. In
      aggregate, these data demonstrate the presence of a low affinity passive Ca2+
      influx pathway in BLMV which displays characteristics similar to the low affinity
      Ca2+ influx component detected in parotid acinar cells following internal Ca2+
      store depletion.

PMID- 9538508
TI  - Sodium-dependent and -independent choline uptake by type II epithelial cells from
      rat lung.
AB  - The uptake of 3H-labeled choline by a suspension of isolated type II epithelial
      cells from rat lung has been studied in a Ringer medium. Uptake was linear for 4
      min at both 0.1 microM and 5.0 microM medium choline; at 5 microM, only 10% of
      the label was recovered in a lipid fraction. Further experiments were conducted
      at the low concentration (0.1 microM), permitting characterization of the
      properties of high-affinity systems. Three fractions of choline uptake were
      detected: (i) a sodium-dependent system that was totally inhibited by
      hemicholinium-3 (HC-3); (ii) a sodium-independent uptake, when Na+ was replaced
      by Li+, K+ or Mg2+, inhibited by HC-3; (iii) a residual portion persisting in the
      absence of Na+ and unaffected by HC-3. Choline uptake was sigmoidally related to
      the medium Na+ concentration. Kinetic properties of the uptake of 0.1 microM 3H
      choline in the presence and absence of medium Na+ were examined in two ways. (a)
      Inhibition by increasing concentrations of unlabeled choline (0.5-100 microM) was
      consistent with the presence of two Michaelis-Menten-type systems in the presence
      of Na+; a Na(+)-dependent portion (a mean of 0.52 of the total) had a K(m) for
      choline of 1.5 microM while K(m) in the absence of Na+ (Li+ substituting) was
      18.6 microM. (b) Inhibition by HC-3 (0.3-300 microM) gave Ki values of 1.7 microM
      and 5.0 microM HC-3 for the Na(+)-dependent and -independent fractions. The
      apparent K(m) of the Na(+)-dependent uptake is lower than that reported
      previously for lung-derived cells and is in the range of the K(m) values reported
      for high-affinity, Na(+)-dependent choline uptake by neuronal cells.

PMID- 9538509
TI  - Membrane potential mediates H(+)-ATPase dependence of "degradative pathway"
      endosomal fusion.
AB  - In some epithelial cell lines, the uptake and degradation of proteins is so
      pronounced as to be regarded as a specialized function known as "degradative
      endocytosis." The endosomal pathways of the renal proximal tubule and the
      visceral yolk sac share highly specialized structures for "degradative
      endocytosis." These endosomal pathways also have a unique distribution of their
      H(+)-ATPase, predominantly in the subapical endosomal pathway. Previous studies
      provide only indirect evidence that H(+)-ATPases participate in endosomal fusion
      events: formation of vesicular intermediates between early and late endosomes is
      H(+)-ATPase dependent in baby hamster kidney cells, and H(+)-ATPase subunits bind
      fusion complex proteins in detergent extracts of fresh rat brain. To determine
      directly whether homotypic endosomal fusion is H(+)-ATPase dependent, we
      inhibited v-type H(+)-ATPase during flow cytometry and cuvette-based fusion
      assays reconstituting endosomal fusion in vitro. We report that homotypic fusion
      in subapical endosomes derived from rat renal cortex, and immortalized visceral
      yolk sac cells in culture, is inhibited by the v-type H(+)-ATPase specific
      inhibitor bafilomycin A1. Inhibition of fusion by H(+)-ATPase is mediated by the
      membrane potential as collapsing the pH gradient with nigericin had no effect on
      homotypic endosomal fusion, while collapsing the membrane potential with
      valinomycin inhibited endosomal fusion. Utilizing an in vitro reconstitution
      assay this data provides the first direct evidence for a role of v-type H(+)
      ATPase in mammalian homotypic endosomal fusion.

PMID- 9538510
TI  - Chemical gating of heteromeric and heterotypic gap junction channels.
AB  - Gap junction channels contain two hemichannels (connexons), each being a connexin
      (Cx) hexamer. In cells expressing multiple connexins, heteromeric connexons are
      believed to form, whereas cell pairs expressing different connexins generate
      heterotypic channels. To define gating behavior of heteromeric and heterotypic
      channels, CO2-induced gating was tested in Xenopus oocyte pairs expressing Cx32,
      or 5R/N (Cx32 mutant), as well as in pairs in which one oocyte (mx) expressed a
      50/50 mixture of Cx32 and 5R/N and the other either the mixture (mx), Cx32 (32)
      or 5R/n (R/N). In 5R/N, replacement of 5 C-terminus arginines with asparagines
      greatly increased CO2 sensitivity. In response to 3 and 15 min CO2 exposures,
      junctional conductance (Gj) decreased to 85% and 47%, in 32-32 pairs, and to 7%
      and 0.9%, in R/N-R/N pairs, respectively. In mx-mx and mix-32 pairs, Gj decreased
      to similar values (33% and 35%, respectively) with 15 min CO2. The sensitivity of
      mx-R/N pairs was similar to that of heterotypic 32-R/N pairs, as Gj dropped to
      36% and 38%, respectively, with 3 min CO2. Monoheteromeric (mx-32 and mx-R/N) and
      biheteromeric (mx-mx) channels behaved as if Cx32 were dominant, suggesting that
      hemichannel sensitivity is not an average of the sensitivities of its connexin
      monomers. In contrast, heterotypic channels behaved as if the two hemichannels of
      a cell-cell channel had no influence on each other.

PMID- 9538511
TI  - MAGE Xp-2: a member of the MAGE gene family isolated from an expression library
      using systemic lupus erythematosus sera.
AB  - Two regions of the genome contain members of the MAGE gene family; Xq27-qter and
      Xp21.3. We isolated a transcript, MAGE Xp-2, by screening a cDNA library from the
      human epithelial carcinoma cell line, HEp-2, using autoantibodies from patients
      with systemic lupus erythematosus (SLE). The open reading frame (ORF) of MAGE Xp
      2 is entirely contained in exon 4, a signature feature of the MAGE gene family.
      While MAGE Xp-2 shares genomic homology with MAGE Xp-1, the predicted proteins
      are quite divergent. Specific primers were designed to reliably distinguish
      between MAGE Xp-1 and MAGE Xp-2 expression. MAGE Xp-2 is expressed in testis, but
      not in other normal tissues. It is also expressed strongly in two of seven
      melanoma cell lines and one of four breast carcinomas. MAGE gene expression may
      be important not only for tumor recognition and cancer therapy, but, because it
      is the apparent target of autoantibodies in SLE sera, it may also play a role in
      autoimmune diseases.

PMID- 9538512
TI  - Porcine cerebroside sulfate activator (saposin B) secondary structure: CD, FTIR,
      and NMR studies.
AB  - Cerebroside sulfate activator protein (CSAct or saposin B) is one of a group of
      heat stable, low-molecular-weight proteins that appear to share a common
      structural motif. These have been referred to as saposin-like proteins and are
      thought to share a multiple amphipathic helical barrel structure with a conserved
      pattern of disulfide linkages. Porcine kidney CSAct was prepared in high purity
      and consisted of three major glycosylated subforms. The protein was studied by
      physical-chemical methods and evaluated by various methods for structural
      prediction. All suggest that CSAct has high amounts of alpha-helical conformation
      and little if any beta-sheet. Circular dichroism (CD) studies indicate 45-50%
      helical conformation depending on buffer and temperature. There was only a
      moderate loss in helical content with increasing temperature and no indication of
      thermal denaturation. Fourier transform infrared spectroscopy (FTIR) measurements
      on deuterium hydrated self-films also indicated a predominantly helical
      structure. Helical axis orientation was investigated by both oriented CD and FTIR
      dichroism, which suggested that the helical axes were roughly parallel and
      oriented along the axis of the surface on which the self-films had been
      deposited. One-dimensional nuclear magnetic resonance spectra showed large
      chemical shift dispersion, indicating a defined tertiary structure with little
      variation between 6 and 85 degrees C. NOESY spectra failed to show the strong NOE
      cross peaks expected for a highly helical conformation. This may indicate short
      term conformational flexibility within the helices or molecular aggregation at
      the high protein concentrations employed. These observations are consistent with
      the 3-4-helix bundle motif suggested for saposin-like proteins by various
      predictive algorithms.

PMID- 9538513
TI  - Human UDP-galactose 4' epimerase (GALE) gene and identification of five missense
      mutations in patients with epimerase-deficiency galactosemia.
AB  - The galactosemias are a series of three inborn errors of metabolism caused by
      deficiency of any one of the three human galactose-metabolic enzymes:
      galactokinase (GALK), galactose-1-phosphate uridyl transferase (GALT), and UDP
      galactose 4' epimerase (GALE). We report here the characterization of the entire
      coding sequence of the GALE gene and screening for mutations in epimerase
      deficient individuals. The human GALE gene is about 4 kb in size and is divided
      into 11 exons on chromosome band 1p36. We have identified five mutations in the
      GALE gene of epimerase-deficient galactosemia patients. The patients were either
      homozygotes or compound heterozygotes for mutations. These results confirm that
      epimerase-deficiency galactosemia is the result of missense mutations in the GALE
      gene and indicate that the disease is characterized by extensive allelic
      heterogeneity.

PMID- 9538514
TI  - Two novel slavic point mutations in the low-density lipoprotein receptor gene in
      patients with familial hypercholesterolemia from St. Petersburg, Russia.
AB  - Using PCR-single-strand conformation polymorphism analysis, followed by
      sequencing of the abnormal samples, two novel point mutations in the 5' end of
      the fourth exon of the low-density lipoprotein receptor gene were found in two
      Russian families with familial hypercholesterolemia. These missense mutations
      consist of C127W and C139G transitions and result in a loss of one of three
      disulfide bonds in the fourth cysteine-rich repeat of the ligand-binding domain
      of the low-density lipoprotein receptor. Hypercholesterolemia segregated with the
      identified mutations.

PMID- 9538515
TI  - Prevalence of the methylenetetrahydrofolate reductase (MTHFR) C677T mutation in
      patients with varicose veins of lower limbs.

PMID- 9538516
TI  - DIVSEL and COMPLIB--strategies for the design and comparison of combinatorial
      libraries using pharmacophoric descriptors.
AB  - Screening synthetic combinatorial libraries may facilitate rapid drug lead
      discovery by substantially increasing the number of molecules tested. Drug
      discovery efficiency and productivity can be further improved by designing
      libraries to maximize their molecular diversity or by comparing them to existing
      collections of compounds and/or libraries to select those that complement the
      properties already well represented. In this paper we describe two strategies to
      aid in the design and comparison of combinatorial libraries. The methods employ
      multi-pharmacophore three-dimensional (3D) descriptors in combination with two
      recent proposals for dissimilarity-based compound selection and library
      comparison. This method allows the design to be performed in product space and
      library comparison to consider all pair-wise intermolecular contributions to the
      diversity.

PMID- 9538517
TI  - Identification of biological activity profiles using substructural analysis and
      genetic algorithms.
AB  - A substructural analysis approach is used to calculate biological activity
      profiles, which contain weights that describe the differential occurrences of
      generic features (specifically, the numbers of hydrogen-bond donors and
      acceptors, the numbers of rotatable bonds and aromatic rings, the molecular
      weights, and the 2 kappa alpha descriptors) in active molecules taken from the
      World Drug Index and in (presumed) inactive molecules taken from the SPRESI
      database. Even with such simple structural descriptors, the profiles discriminate
      effectively between active and inactive compounds. The effectiveness of the
      approach is further increased by using a genetic algorithm for the calculation of
      the weights comprising a profile. The methods have been successfully applied to a
      number of different data sets.

PMID- 9538518
TI  - Mining the NCI anticancer drug discovery databases: genetic function
      approximation for the QSAR study of anticancer ellipticine analogues.
AB  - The U.S. National Cancer Institute (NCI) conducts a drug discovery program in
      which approximately 10,000 compounds are screened every year in vitro against a
      panel of 60 human cancer cell lines from different organs of origin. Since 1990,
      approximately 63,000 compounds have been tested, and their patterns of activity
      profiled. Recently, we analyzed the antitumor activity patterns of 112
      ellipticine analogues using a hierarchical clustering algorithm. Dramatic
      coherence between molecular structures and activity patterns was observed
      qualitatively from the cluster tree. In the present study, we further investigate
      the quantitative structure-activity relationships (QSAR) of these compounds, in
      particular with respect to the influence of p53-status and the CNS cell
      selectivity of the activity patterns. Independent variables (i.e., chemical
      structural descriptors of the ellipticine analogues) were calculated from the
      Cerius2 molecular modeling package. Important structural descriptors, including
      partial atomic charges on the ellipticine ring-forming atoms, were identified by
      the recently developed genetic function approximation (GFA) method. For our data
      set, the GFA method gave better correlation and cross-validation results (R2 and
      CVR2 were usually approximately 0.3 higher) than did classical stepwise linear
      regression. A procedure for improving the performance of GFA is proposed, and the
      relative advantages and disadvantages of using GFA for QSAR studies are
      discussed.

PMID- 9538519
TI  - Superposition of three-dimensional chemical structures allowing for
      conformational flexibility by a hybrid method.
AB  - The superposition of three-dimensional structures is the first task in the
      evaluation of the largest common three-dimensional substructure of a set of
      molecules. This is an important step in the identification of a pharmacophoric
      pattern for molecules that bind to the same receptor. The superposition method
      described here combines a genetic algorithm with a numerical optimization method.
      A major goal is to adequately address the conformational flexibility of ligand
      molecules. The genetic algorithm optimizes in a nondeterministic process the size
      and the geometric fit of the substructures. The geometric fit is further improved
      by changing torsional angles combining the genetic algorithm and the directed
      tweak method. This directed tweak method is based on a numerical quasi-Newton
      optimization method. Only one starting conformation per molecule is necessary.
      Molecules having several rotatable bonds and quite different initial
      conformations are modified to find large structural similarities. A set of
      angiotensin II antagonists is investigated to illustrate the performance of the
      method.

PMID- 9538520
TI  - Rational combinatorial library design. 1. Focus-2D: a new approach to the design
      of targeted combinatorial chemical libraries.
AB  - We describe a new computational approach, called Focus-2D, to the rational design
      of targeted combinatorial chemical libraries. This approach is based on the
      hypothesis that structurally similar compounds display similar biological
      activity profiles. Building blocks that are used in a combinatorial chemical
      synthesis are randomly assembled to produce virtual library compounds. Individual
      library compounds are represented by Kier-Hall topological descriptors. Molecular
      similarities between compounds are evaluated quantitatively by modified pairwise
      Euclidean distances in multidimensional descriptor space. Simulated annealing is
      used to search the potentially large structural space of virtual chemical
      libraries to identify compounds similar to lead molecules. Frequency analysis of
      building block composition of selected virtual compounds identifies building
      blocks that can be used in combinatorial synthesis of chemical libraries with
      high similarity to the lead molecules. We show that this method correctly
      identifies building found in active peptoids with adrenergic or opioid
      activities.

PMID- 9538521
TI  - Rational combinatorial library design. 2. Rational design of targeted
      combinatorial peptide libraries using chemical similarity probe and the inverse
      QSAR approaches.
AB  - We have developed a novel strategy for rational design of targeted peptide
      libraries. The goal of this method is to select a subset of natural amino acids
      that are most likely to be present in active peptides for the synthesis of
      library. Two different protocols are employed where chemical structures of
      peptides are described either by topological indices or by a combination of
      physicochemical descriptors for individual amino acids. The selection of a
      peptide as a candidate for the targeted library is based either on its chemical
      similarity to a biologically active probe or on its biological activity predicted
      from a preconstructed quantitative structure-activity (QSAR) equation. The
      optimization of the library is achieved by means of genetic algorithms (GA). This
      method was tested by rational design of the library with bradykinin-potentiating
      activity. Twenty-eight bradykinin-potentiating pentapeptides were used as a
      training set for the development of a QSAR equation, and, alternatively, two
      active pentapeptides, VEWAK and VKWAP, were used as probe molecules. In each
      case, the frequency distribution of amino acids in the top 100 peptides suggested
      by the method resembles the frequency distribution of amino acids found in the
      active peptides. The results obtained after GA optimization also compared
      favorably with those obtained by the exhaustive analysis of all possible 3.2
      million pentapeptides.

PMID- 9538522
TI  - Probing viruses with mass spectrometry.
AB  - Mass spectrometry offers a new perspective on the solution and gas-phase
      properties of viruses. Its broad application to local and global viral structure
      provides unique insights into many biological processes, including viral-antibody
      binding, protein-protein interactions and protein dynamics. Mass measuring viral
      proteins is now routine and since viruses are typically well characterized, in
      that the capsid proteins and DNA (or RNA) sequences are known, identifying a
      virus based on the mass of the protein and enzymatic digestion fragments is
      relatively straightforward. Using mass spectrometry, this paper describes the
      identification of viral protein post-translational modifications such as
      myristoylation, phosphorylation and disulfide bridging. Furthermore,
      complementary data obtained with mass spectrometry and x-ray crystallography
      demonstrate that viruses are highly dynamic particles whose viral capsid's
      mobility could, until recently, be inferred only from inherently static
      spectroscopic methods. Lastly, mass spectrometry has been applied on a global
      scale via the mass measurement of entire intact viruses. Given the general
      utility of mass spectrometry, its continuing development should further its
      application to viral dynamics, structure, function and identification.

PMID- 9538523
TI  - Electrospray ionization mass spectrometry of metalloporphyrins.
AB  - The magnesium, nickel, copper, zinc and vanadium metalloporphyrins from
      octaethylporphyrin, etioporphyrin I and tetraphenylporphyrin were characterized
      using electrospray ionization mass spectrometry (ESI-MS). The ion abundance of
      each of the porphyrins present in binary mixtures was monitored as a function of
      the porphyrin concentration and is dependent on the metalloporphyrin oxidation
      potential. It was found that, for binary mixtures of metalloporphyrins whose
      oxidation potentials differ by less than 0.1 V, the resulting ion abundance of
      each species is directly proportional to the concentration of each analyte in the
      mixture. For binary mixtures whose oxidation potentials differ by more than 0.1
      V, relative abundances of the radical cations of each metalloporphyrin are
      determined by the oxidation potential and concentration of each metalloporphyrin
      with the analyte of lowest oxidation potential being ionized preferentially. The
      ability to ionize selectively one porphyrin over another in a binary mixture
      offers the potential to use ESI-MS for the qualitative analysis of porphyrins
      present in complex mixtures.

PMID- 9538524
TI  - Dimethyl ether chemical ionization mass spectrometry of alpha-amino acids.
AB  - Dimethyl ether (DME) is a useful reagent gas for the characterization of a
      variety of diverse biologically important or environmentally significant classes
      of compounds. In this work the gas-phase ion-molecule reactions of DME with 23
      alpha-amino acids were investigated and the collision-induced dissociation (CID)
      fragmentations of the protonated molecules and their most prominent adduct ions
      were studied. The identities and relative abundances of the adduct ions varied
      widely and, not unexpectedly, were dependent on the nature of the R substituent
      in H2NCH(R)CO2H. With a few exceptions, notably serine and threonine, protonated
      molecules and [M + 13]+ adduct ions were highly abundant, and in most cases
      methoxymethylene cations [M + 45]+ were also prominent. The solvated
      methoxymethylene cation [M + 91]+ was seen in very modest abundance or not at
      all, except for serine and threonine, when it was the most abundant. CID
      fragmentations of the protonated molecules generated in the DME plasma showed
      similar characteristics to those generated by fast atom bombardment in that
      sequential elimination of H2O and CO to the iminium ion was the predominant
      process in the majority of cases, and was also accompanied by the loss of NH3 in
      the cases of cysteine, glutamine, ornithine and lysine. Loss of NH3 alone was the
      predominant process for tryptophan, and for arginine and methionine the
      fragmentations were dominated by the guanidino and methylthio substituents,
      respectively.

PMID- 9538525
TI  - Rapid methods for screening low molecular mass compounds non-covalently bound to
      proteins using size exclusion and mass spectrometry applied to inhibitors of
      human cytomegalovirus protease.
AB  - General and rapid methods were developed for determining the extent of non
      covalent binding between small molecules and proteins, using the model system of
      human cytomegalovirus protease and several drug candidates which inhibit the
      protease by non-covalently binding to it. The assay was performed by off-line
      coupling of size-exclusion methods with mass spectrometry in the following
      manner. The protease and inhibitor were incubated together under native
      conditions and then subjected to separation based on size, by use of a spin
      column (gel permeation chromatography) and/or a microconcentrator
      (ultrafiltration). The spin column selectively passed the high molecular mass
      (M(r)) protease and trapped low M(r) molecules. Alternatively, the
      microconcentrator passed low M(r) molecules and retained the protease. If the
      inhibitor bound non-covalently to the protease, both the inhibitor and protease
      passed through the spin column (or were retained by the microconcentrator).
      Electrospray ionization mass spectrometry was used to assay the spin column
      eluate (or the microconcentrator retentate) and to characterize the amounts of
      protease and inhibitor based on known standards. An advantage of these techniques
      is that a mixture containing inhibitors can be analyzed in the presence of the
      protease, and inhibitors with the greatest binding affinity can be identified.
      Non-covalent binding specificity was demonstrated using spin columns by comparing
      the binding affinity of inhibitors using several mutants of cytomegalovirus
      protease. The techniques described are applicable to the rapid screening of
      compound libraries for selecting substances which bind non-covalently to a known
      protein.

PMID- 9538526
TI  - Rapid screening of destruxins by liquid chromatography/mass spectrometry.
AB  - A liquid chromatographic/mass spectrometric (LC/MS) method utilizing an
      atmospheric pressure chemical ionization (APCI) interface and in-source
      collisionally induced dissociation (CID) was developed for the rapid screening of
      the cyclic hexadepsipeptides destruxins, produced by the fungi Metarhizium
      anisopliae and Trichothecium roseum. The APCI mass spectra are fully consistent
      with the high-energy CID data but the sequence ions are abundant over the whole
      mass range. In addition to 22 known destruxins, two new representatives of this
      family were detected by LC/MS analysis: destruxin Ed1 and roseotoxin A were
      isolated and their structures were inferred from MS/MS and NMR data.

PMID- 9538527
TI  - Blood-brain barrier penetration of 3-aminopropyl-n-butylphosphinic acid (CGP
      36742) in rat brain by microdialysis/mass spectrometry.
AB  - The detection and quantitation of the novel drug 3-aminopropyl-n-butylphosphinic
      acid (APBP), also known as CGP 36742, was performed in vivo using microdialysis
      and tandem mass spectrometry. This drug is a GABA-B antagonist with high
      specificity for GABA-B receptors. Animals received doses of 100, 200, 500 and
      1000 mg kg-1 of the drug either intravenously or per os (p.o.). Microdialysis
      probes, placed by stereotaxis in either the frontal cortex or third ventricle of
      the rat, were used to collect dialyzate samples over several hours. Samples were
      then analyzed by micro-electrospray tandem mass spectrometry to achieve a
      molecular mass and structure specific analysis. For example, animals receiving a
      dose of 100 mg kg-1 p.o. showed a peak concentration of approximately 10 microM
      in the dialyzate. For comparison, tissue and plasma samples of the drug were
      measured under the same conditions using gas chromatography/mass spectrometry.
      This work demonstrates that the microdialysis technique in combination with the
      molecular specificity and high sensitivity of micro-electrospray tandem mass
      spectrometry can be used to study the time course of the appearance of unmodified
      drug in the brain of a single animal.

PMID- 9538528
TI  - High-precision continuous-flow isotope ratio mass spectrometry.
AB  - Although high-precision isotope determinations are routine in many areas of
      natural science, the instrument principles for their measurements have remained
      remarkably unchanged for four decades. The introduction of continuous-flow
      techniques to isotope ratio mass spectrometry (IRMS) instrumentation has
      precipitated a rapid expansion in capabilities for high-precision measurement of
      C, N, O, S, and H isotopes in the 1990s. Elemental analyzers, based on the flash
      combustion of solid organic samples, are interfaced to IRMS to facilitate routine
      C and N isotopic analysis of unprocessed samples. Gas/liquid equilibrators have
      automated O and H isotopic analysis of water in untreated aqueous fluids as
      complex as urine. Automated cryogenic concentrators permit analysis at part-per
      million concentrations in environmental samples. Capillary gas chromatography
      interfaced to IRMS via on-line microchemistry facilitates compound-specific
      isotope analysis (CSIA) for purified organic analytes of 1 nmol of C, N, or O. GC
      based CSIA for hydrogen and liquid chromatography-based interfaces to IRMS have
      both been demonstrated, and continuing progress promises to bring these advances
      to routine use. Automated position-specific isotope analysis (PSIA) using
      noncatalytic pyrolysis has been shown to produce fragments without appreciable
      carbon scrambling or major isotopic fractionation, and shows great promise for
      intramolecular isotope ratio analysis. Finally, IRMS notation and useful
      elementary isotopic relationships derived from the fundamental mass balance
      equation are presented.

PMID- 9538529
TI  - Developments in cardiovascular ultrasound: Part 1: Signal processing and
      instrumentation.
AB  - One of the major contributions to the improvement of spectral Doppler and colour
      flow imaging instruments has been the development of advanced signal-processing
      techniques made possible by increasing computing power. Model-based or parametric
      spectral estimators, time-frequency transforms, station-arising algorithms and
      spectral width correction techniques have been investigated as possible
      improvements on the FFT-based estimators currently used for real-time spectral
      estimation of Doppler signals. In colour flow imaging some improvement on
      velocity estimation accuracy has been achieved by the use of new algorithms but
      at the expense of increased computational complexity compared with the
      conventional autocorrelation method. Polynomial filters have been demonstrated to
      have some advantages over IIR filters for stationary echo cancellation. Several
      methods of velocity vector estimation to overcome the problem of angle dependence
      have been studied, including 2D feature tracking, two and three beam approaches
      and the use of spectral width in addition to mean frequency. 3D data acquisition
      and display and Doppler power imaging have also been investigated. The use of
      harmonic imaging, using the second harmonic generated by encapsulated bubble
      contrast media, seems promising particularly for imaging slow flow. Parallel
      image data acquisition using non-sequential scanning or broad beam transmission,
      followed by simultaneous reception along a number of beams, has been studied to
      speed up 'real-time' imaging.

PMID- 9538530
TI  - Motorised resection device for transurethral resection of the prostate: a
      laboratory evaluation.
AB  - Transurethral resection of the prostate is the most common method of relieving
      urinary outflow obstruction secondary to prostatic enlargement. However, this
      procedure can be responsible for various complications, including irrigant-fluid
      absorption and blood loss, both of which are strongly dependent on operation
      duration time. To reduce the latter, a new resection device has been designed for
      transurethral prostatectomy. The device basically consists of a rotating cutting
      loop controlled externally, with three degrees of freedom, to fit the adenoma
      shape. Its performance is assessed in vitro by drilling conical and semi
      ellipsoidal cavities in agar gel models. The mean difference between the
      calculated and obtained cavity volumes is 3% (SD = 0.9%). The volume cutting
      rate, found to be independent of the type of cavity drilled, is equal to 2.9 +/-
      0.3 cm3 min-1. The advantages of this motorised resection device prototype are
      reduction in operation duration and accuracy of the resected volume. In vivo
      resection of a 20 cm3 adenoma in less than 15 min can be expected.

PMID- 9538531
TI  - Can blood flow in separate small tubes be quantitatively assessed by high
      resolution laser Doppler imaging?
AB  - A method is suggested for quantitative flow assessment of whole-blood perfusing
      tubes with diameters in the range from 500 microns to 1.5 mm, for velocities
      below 9 mm s-1. The algorithm is based both on the Doppler broadening of
      backscattered laser light and the magnitude of the diameter of the perfused tube.
      A bandwidth-modified high-resolution laser Doppler perfusion imaging system is
      used to record the Doppler broadening. A flow model, consisting of a linearly
      narrowing tube (inner diameter 620-1330 microns), is connected to a precision
      infusion pump and perfused by human whole blood of volume flows ranging from 0 to
      6.6 mm3 s-1. Empirical data are fitted into a regression model, and the
      parameters of the algorithm can be determined, resulting in a correlation
      coefficient of 0.975 between the predicted and true volume flows. Using this
      algorithm, volume flows in tubes of inner diameters of 500 microns, 750 microns
      and 1.4 mm are predicted, with accuracies corresponding to correlation
      coefficients of 0.994, 0.993 and 0.996.

PMID- 9538532
TI  - In vivo comparison of scanning technique and wavelength in laser Doppler
      perfusion imaging: measurement in knee ligaments of adult rabbits.
AB  - At present, there are only two laser Doppler perfusion imaging systems (LDIs)
      manufactured for medical applications: a 'stepwise' and a 'continuous' scanning
      LDI. The stepwise scanning LDI has previously been investigated and compared with
      coloured microsphere determined standardised flow. The continuous scanning LDI is
      investigated and compared with the stepwise scanning LDI for its ability to
      measure in vivo, hypoaemic, ligament tissue blood flow changes. The continuous
      scanning system was supplied with two lasers, red and near infrared (NIR),
      allowing for additional assessment of the effect of wavelength on imaging
      ligament perfusion. Perfusion images were obtained from surgically exposed rabbit
      medial collateral ligaments (MCL). Continuous and stepwise LDI scans were
      compared using correlation and linear regression analysis of image. averages and
      standard deviations. Using the same method of analysis, LDI measurements using
      red and NIR lasers indicated a high degree of correlation, at least over the
      ranges of perfusion assessed, indicating that red and NIR lasers measure similar
      regions of flow in the rabbit MCL. These experiments confirm that both LDI
      techniques provide a valid in vivo measure of dynamic changes in connective
      tissue perfusion and could have significant impact on the understanding and
      treatment of joint injury and arthritis.

PMID- 9538533
TI  - Computerised infrared imaging system for studying thermal activation on the skull
      following somatic stimulation in small animals.
AB  - A computerised infrared imaging system has been developed to measure infrared
      radiation as a means of functionally mapping the cerebral cortex. In two species
      of small mammal, rat and gerbil, the authors localised the thermal changes at the
      skull overlying the somatic sensory cortex following somatic stimulation of the
      mystacial vibrissae. Though typically small in magnitude, a thermal response
      could be detected through the skull. To enhance detection sensitivity, a number
      of measures were taken to improve various aspects of data acquisition, stimulus
      delivery and control of experimental conditions. Regarding data analysis, a
      coordinate system based on skull landmarks was adopted to localise thermally
      active regions for comparison across animals of the same species. To extract the
      region of weak temperature changes, a coarse-to-fine detection strategy was
      developed, which searched automatically for clusters of temporally- and spatially
      correlated pixels above a data-driven threshold. Thus, the dynamic aspect of the
      thermal changes at any region of interest on the skull could be studied
      efficiently. The detection algorithm was tested against simulated responses in
      addition to empirical data obtained from animals. All of the above software was
      integrated in a user-friendly package.

PMID- 9538534
TI  - Distribution mapping of ciliary beat frequencies of respiratory epithelium cells
      using image processing.
AB  - Through their rapid periodic actions, the cilia of the human respiratory tract
      play an important role in clearing inhaled noxious particles. An automated method
      is developed, based on an image-processing technique, to measure and analyse
      objectively and quantitatively, ciliary beat frequency (CBF). Microscopic ciliary
      images are transformed into digitised grey images through an image grabber inside
      a PC, and signals are extracted from these, based on an image-subtraction
      algorithm, and are processed through power spectrum analysis using a fast Fourier
      transform (FFT). By means of the FFT power spectrum, maximum peak frequencies are
      detected as CBFs in each partitioned block for the entire digitised field. Using
      these CBFs, distribution maps are composed in various resolutions, showing
      visually the spatial distribution of CBFs through cells and in a single cell. To
      measure CBF variations quantitatively, phenylephrine hydrochloride is used, and
      the changes in CBF influenced by its concentration and duration are observed.

PMID- 9538535
TI  - Minimally invasive 3D data registration in computer and robot assisted total knee
      arthroplasty.
AB  - Computer and robot assisted surgery is concerned with the improvements achievable
      by using computer methods and robotic devices to plan and execute surgical
      interventions. The registration of different coordinate frames, often achieved
      through the matching of 3D data sets, represents a crucial step connecting
      planning and execution. Orthopaedic surgery already features a number of
      functioning applications which include registration routines relying on
      presurgically implanted fiducial markers. Replacing such invasive routine with
      non-fiducial registration procedures is regarded as a necessary step towards a
      minimisation of surgical invasiveness. A minimally invasive registration
      technique based on the iterative closest point algorithm is presented and
      conceived for a specific computer and robot assisted orthopaedic reconstructive
      intervention, namely total knee arthroplasty. The whole surgical protocol is
      examined in detail and the experimental results, relative to tests performed on
      synthetic and animal specimens, are thoroughly reported and discussed. The
      authors indicate that the proposed registration approach is well-suited for the
      relevant application and appropriate for in vivo testing.

PMID- 9538536
TI  - Morphometric evaluations of personalised 3D reconstructions and geometric models
      of the human spine.
AB  - In the past, several techniques have been developed to study and analyse the 3D
      characteristics of the human spine: multi-view radiographic or biplanar 3D
      reconstructions, CT-scan 3D reconstructions and geometric models. Extensive
      evaluations of three of these techniques that are routinely used at Sainte
      Justine Hospital (Montreal, Canada) are presented. The accuracy of these methods
      is assessed by comparing them with precise measurements made with a coordinate
      measuring machine on 17 thoracic and lumbar vertebrae (T1-L5) extracted from a
      normal cadaveric spine specimen. Multi-view radiographic 3D reconstructions are
      evaluated for different combinations of X-ray views: lateral (LAT), postero
      anterior with normal incidence (PA0 degree) and postero-anterior with 20 degrees
      angled down incidence (PA20 degrees). The following accuracies are found for
      these reconstructions obtained from different radiographic setups: 2.1 +/- 1.5 mm
      for the combination with PA0 degree-LAT views, and 5.6 +/- 4.5 mm for the PA0
      degree-PA20 degrees stereopair. Higher errors are found in the postero-anterior
      direction, especially for the PA0 degree-PA20 degrees view combination. Pedicles
      are found to be the most precise landmarks. Accuracy for CT-scan 3D
      reconstructions is about 1.1 +/- 0.8 mm. As for a geometric model built using a
      multiview radiographic reconstruction based on six landmarks per vertebra,
      accuracies of about 2.6 +/- 2.4 mm for landmarks and 2.3 +/- 2.0 mm for
      morphometric parameters are found. The geometric model and 3D reconstruction
      techniques give accurate information, at low X-ray dose. The accuracy assessment
      of the techniques used to study the 3D characteristics of the human spine is
      important, because it allows better and more efficient quantitative evaluations
      of spinal dysfunctions and their treatments, as well as biomechanical modeling of
      the spine.

PMID- 9538537
TI  - Spectral analysis of heart rate fluctuations and optimum thermal management for
      low birth weight infants.
AB  - Spectral analysis of heart rate variability is studied in 10 healthy growing
      premature infants to investigate the changes in autonomic balance achieved as a
      function of changes in skin temperature. Heart rate is obtained from ECG
      recordings and the power spectrum of beat-to-beat heart rate fluctuations is
      computed. The infants maintain mean rectal temperature within 36.3-37.2 degrees
      C, while skin temperature changes. The respiratory rate does not change at the
      different servocontrol set points. Heart rate is found to increase slightly, but
      consistently. The low-frequency band (0.02-0.2 Hz), reflecting the interplay of
      the sympathetic and parasympathetic tone and known to be maximum at the
      thermoneutral zone, is maximum at 35.5 and 36 degrees C and decreases gradually
      to a lower level at a servocontrol temperature of 36.5-37 degrees C. The high
      frequency band (0.2-2.0 Hz), coinciding with the respiratory peak and reflecting
      parasympathetic activity, is significantly elevated at 36 degrees C (p < 0.01).
      The minimum low: high ratio, indicating the minimum sympathetic-parasympathetic
      balance and possibly reflecting the most comfortable conditions, occurs at 36
      degrees C, although the differences are not statistically significant.
      Servocontrol skin temperature may thus be adapted, and possibly selected at 36
      degrees C for growing premature infants in an attempt to achieve thermal comfort
      and more balanced autonomic activity.

PMID- 9538538
TI  - Detection of life-threatening cardiac arrhythmias using the wavelet
      transformation.
AB  - Time-frequency wavelet theory is used for the detection of life threatening
      electrocardiography (ECG) arrhythmias. This is achieved through the use of the
      raised cosine wavelet transform (RCWT). The RCWT is found to be useful in
      differentiating between ventricular fibrillation, ventricular tachycardia and
      atrial fibrillation. Ventricular fibrillation is characterised by continuous
      bands in the range of 2-10 Hz; ventricular tachycardia is characterised by two
      distinct bands: the first band in the range of 2-5 Hz and the second in the range
      of 6-8 Hz; and atrial fibrillation is determined by a low frequency band in the
      range of 0-5 Hz. A classification algorithm is developed to classify ECG records
      on the basis of the computation of three parameters defined in the time-frequency
      plane of the wavelet transform. Furthermore, the advantage of localising and
      separating ECG signals from high as well as intermediate frequencies is
      demonstrated. The above capabilities of the wavelet technique are supported by
      results obtained from ECG signals obtained from normal and abnormal subjects.

PMID- 9538539
TI  - Vibration plethysmography: a method for studying the visco-elastic properties of
      finger arteries.
AB  - Vibration plethysmography records changes in vascular volume produced by fast
      vibrations of cuff pressure. From these, waveforms of dynamic vascular compliance
      (DVC) are obtained. A total of 46 recordings of DVC, photo-electric plethysmogram
      (PG), cuff pressure (CP), and indirect blood pressure (BP) are performed on two
      adjacent fingers (third and fourth) in 23 healthy subjects. The shape and
      polarity of the DVC waveform markedly depends upon CP or transmural pressure (TP)
      (TP = BP - CP). The correlation coefficient between DVC and PG waveforms is
      nearly -1 at negative mean TP, near zero at zero TP, and approaches +1 at
      positive TP. For CP moving between systolic and diastolic BP, the DVC waveform
      shows a diastolic peak, with its maximum close to the zero value of instantaneous
      TP. xy-diagrams of PG against TP and of DVC against TP plotted for the diastolic
      phase of single pulses reveal a close coincidence of the DVC peak with the
      maximum slope of the PG/TP curve. A similar relationship appears when slow
      changes in PG and the amplitude of PG pulse waves are plotted against mean TP.

PMID- 9538540
TI  - Interaction between steady flow and individualised compliant segments:
      application to upper airways.
AB  - To describe upper airway obstruction in patients with sleep apnea syndrome, the
      steady state solutions of a simple model of local pharyngeal obstruction were
      studied. Importantly, the present model embodies a series of two individualised
      elements, each having its own compliance, which enables the consideration, from a
      conceptual point of view, of local differences in anatomical and physiological
      properties between pharyngeal regions. The evolution of inspiratory flow and area
      variations were predicted using the transmural pressure at the downstream element
      as the controlled variable. Derivation and normalisation of fundamental governing
      equations, written for non-viscous and viscous fluids, reveal very different
      kinds of behaviour, depending on values of the speed index defined from the local
      distensibility, or its modulation by a friction factor for viscous fluid. The two
      element model is able to describe a considerably rich mechanical behaviour,
      including the occurrence of critical conditions when area becomes very high or
      small, i.e. when the distensibility-dependent speed index at the upstream element
      tends toward unity. In spite of its simplicity, not only does the present model
      describe steady state behaviours that resemble the well-known phenomenon of
      choking in an elastic tube, but the viscous fluid conditions also reveal (i) an
      area evolution following a typical doubly folded shape, (ii) the occurrence of a
      close succession maximum and minimum flows which can be seen as a physiological
      'flow plateau'. It is concluded that the concept of interaction behind the two
      element model must be considered as soon as flow interacts in a compliant
      structure characterised by anatomical and/or functional singularities.

PMID- 9538541
TI  - Time-frequency analysis of the muscle sound of the human diaphragm.
AB  - The time-frequency characteristics of muscular sounds (phonomyogram) produced by
      the contraction of the human diaphragm under various contractile states is
      evaluated with the cone-kernel distribution. The results show that the
      instantaneous frequency of the phonomyogram of the diaphragm has a high cross
      correlation (an average of 0.91 +/- 0.06) with the transdiaphragmatic pressure,
      with a delay varying between 25 and 35 ms. The instantaneous frequency response
      of the phonomyogram of the diaphragm shows a behaviour similar to that of the
      frog muscle; it rapidly rises and then fades out. However, the maximum of the
      instantaneous frequency of the phonomyogram of the diaphragm is not proportional
      to the maximum of the transdiaphragmatic pressure. This analysis also
      demonstrates the usefulness of the cone-kernel distribution for studying
      frequency-modulated signals like the muscular sound signals.

PMID- 9538542
TI  - Development and evaluation of a fully automated monophasic action potential
      analysis program.
AB  - A fully automated program has been developed for analysing digitised cardiac
      monophasic action potentials (MAPs) of several animal species. Under diverse
      conditions, the program's performance is evaluated by comparison with high
      resolution manual analysis of action potential duration, MAP detection, baseline
      and plateau determination. For each variable, the differences between both forms
      of analysis are categorised according to species (rabbit, dog or baboon),
      intervention (control, sematilide or LY-190147), rhythm source (sinus or paced),
      and rates. They are then examined using ANOVA (null hypothesis: no difference
      between methods for any category). Intra-group differences are significant for
      baseline selection (p < 0.05), and treatment effects are significant (p < 0.05)
      for one species (baboon). However, the differences found are negligible when
      compared with expected measurement errors. Thus the program reliably detects and
      accurately analyses MAPs, independent of species, drug or pacing. The program's
      strength is its use of simple heuristic algorithms to identify and profile MAP
      signals while rejecting spurious transients. These algorithms focus on the
      procedural aspects of automatic MAP detection and validation, with minimum use of
      complex mathematics. The program's estimated throughput exceeds 8200 MAPs min-1
      on a 50 MHz 1486 DX machine. With available data format conversion packages,
      signals from almost any data-acquisition source can be analysed.

PMID- 9538543
TI  - Supervised mutual-information based feature selection for motor unit action
      potential classification.
AB  - A new supervised mutual information-based feature selection method is presented.
      Using real motor unit action potential (MUAP) data from 10 EMG signals, the
      performances of 32 time-sample feature sets, feature subsets selected using first
      and second-order mutual information and features obtained using linear
      discriminant analysis (LDA) and principal component analysis (PCA) were evaluated
      using a minimum Euclidean distance (MED) classifier. The evaluation showed that
      by using only 20 first-order features or only 15 second-order features mean error
      rates and error rate variations equivalent to using all 32 samples or LDA or PCA
      could be obtained. The computational cost of first-order feature selection was
      considerably less than LDA, PCA and second-order feature selection. The
      performance of first-order features was further evaluated using a more robust
      classifier. Unlike the MED classifier, the robust classifier only assigned a
      candidate MUAP if the assignment was sufficiently certain. For the robust
      classifier the average error rates using 20 features were similar to using the
      full feature set, yet higher assignment rates were obtained. Results from both
      evaluations suggest that the sets of first-order features were an efficient
      representation of lower dimension, which provided high accuracy classification
      with reduced computational requirements.

PMID- 9538544
TI  - Simultaneous identification of eye fixation related potentials and reaction
      related potentials from single-trial signals.
AB  - To obtain the effective components from event related potentials (ERPs), it has
      been necessary to average the waveforms of several trials. ERP data reflect the
      psychophysiological state of a subject. Time variation is an important feature in
      ERP analysis, and so the single-trial method is required. A method is proposed to
      identify simultaneously both eye fixation related potentials (EFRPs) and reaction
      related potentials (RRPs) using wavelength transforms. The EFRP is an ERP
      associated with saccadic eye movement. The RRP is defined as a component similar
      to P300 gained from the reaction signal. Six subjects participate in the oddball
      task. The task takes 30 min for each subject. Electroencephalograms (EEGs),
      electro-oculograms (EOGs) and electromyograms (EMGs) are simultaneously recorded.
      The EFRP is extracted for the offset of saccade from EOG, and the RRP is
      extracted for the onset of reaction from EMG. The results show that the estimated
      waveforms described well each of the components in the EFRP and RRP. Moreover,
      the simulation results show that the amplitudes of the lambda wave are estimated
      to within an error of 4%, and those of the latencies are within 0.4%, with an SNR
      of 4.5dB. Those of P300 were 11 and 4%, respectively. The reliability of the
      method is proved to be sufficient for estimating ERPs.

PMID- 9538545
TI  - Adaptive filtering, modelling and classification of knee joint vibroarthrographic
      signals for non-invasive diagnosis of articular cartilage pathology.
AB  - Interpretation of vibrations or sound signals emitted from the patellofemoral
      joint during movement of the knee, also known as vibroarthrography (VAG), could
      lead to a safe, objective, and non-invasive clinical tool for early detection,
      localisation, and quantification of articular cartilage disorders. In this study
      with a reasonably large database of VAG signals of 90 human knee joints (51
      normal and 39 abnormal), a new technique for adaptive segmentation based on the
      recursive least squares lattice (RLSL) algorithm was developed to segment the non
      stationary VAG signals into locally-stationary components; the stationary
      components were then modelled autoregressively, using the Burg-Lattice method.
      Logistic classification of the primary VAG signals into normal and abnormal
      signals (with no restriction on the type of cartilage pathology) using only the
      AR coefficients as discriminant features provided an accuracy of 68.9% with the
      leave-one-out method. When the abnormal signals were restricted to chondromalacia
      patella only, the classification accuracy rate increased to 84.5%. The effects of
      muscle contraction interference (MCI) on VAG signals were analysed using signals
      from 53 subjects (32 normal and 21 abnormal), and it was found that adaptive
      filtering of the MCI from the primary VAG signals did not improve the
      classification accuracy rate. The results indicate that VAG is a potential
      diagnostic tool for screening for chondromalacia patella.

PMID- 9538546
TI  - Cardiopulmonary monitoring by textile electrodes without subject-awareness of
      being monitored.
AB  - An automated system is developed to monitor cardiopulmonary functions during
      sleep using electrically conductive textiles. The system obviates the need to
      attach transducers or electrodes to the body surface, and the subject can follow
      his or her normal daily routine, wearing regular pajamas to bed. Part of the bed
      sheet consists of electrically conductive textiles under the positions of the
      head, torso and legs. Respiratory activity and electrocardiograms of diagnostic
      quality are observed by means of the electrodes while the subject is sleeping.
      Respiration is sensed by means of electrical capacitance in/around the thorax.
      Data acquisition and storage are fully automated; thus, the subject's awareness
      of being monitored is greatly reduced. This system could detect disorders of
      cardiopulmonary functions at an early stage, if used daily in the home with the
      concept of chronodiagnosis.

PMID- 9538547
TI  - Proposed new bladder volume monitoring device based on impedance measurement.
AB  - A new implantable bladder volume-monitoring device based on the impedance
      measurement of the detrusor muscle is described. The system is completely
      autonomous and forms a mixed-signal (analogue/digital) feedback loop with a neuro
      stimulator to rectify bladder dysfunctions (incontinence and retention) through
      neuromuscular stimulation techniques. A programmable instrumentation amplifier
      and a signal processing block, to eliminate the artefacts caused by the patient's
      movements, have been designed and tested. The layout for the signal processing
      block has been realised in 0.8 micron BiCMOS technology.

PMID- 9538548
TI  - Model for the dielectric properties of human lung tissue against frequency and
      air content.
AB  - Electrical impedance tomographic spectroscopy measurements of the lungs are taken
      from nine normal subjects, in the frequency range 9.6 kHz-1.2 MHz. The results
      show that resistivity rho'FRC relative to functional residual capacity increases
      almost linearly with inspiration volume V, with the slope of the curve increasing
      with frequency f. Resistivity rho'9.6 kHz relative to 9.6 kHz decreases with f.
      rho'9.6 kHz increases with V, at any given frequency. Curves for rho'9.6 kHz show
      a roughly linear trend with log10(f). Based on a discussion of the measurement
      results, a mathematical lung tissue model is designed that involves extra
      capillary blood vessels and alveoli, the walls of which consist of blood-filled
      capillaries, epithelial cells and intercellular liquid. Using this model, the
      increase in rho'FRC with V is explained by the thinning of alveolar walls with
      increasing air content. The almost linear shape of curves for rho'9.6 kHz is
      attributed to four partly overlapping main dispersions caused by extra-capillary
      blood vessels, epithelial cells, blood and the capillary network.

PMID- 9538549
TI  - Transcephalic electrical impedance in the study of cerebral circulation in a
      juvenile pig model.
AB  - Transcephalic electrical impedance offers a technique for non-invasive, cot-side
      monitoring of neonatal cerebral circulation but the exact nature of the signal is
      somewhat ambiguous. The impedance signal is examined in an animal project where
      the ventilator settings are adjusted (20 min-1-10 min-1-40 min-1 for 10 min
      periods each) to produce circulatory changes. Six juvenile pigs are intubated,
      and ECG, arterial blood pressure, carotid flow (CF) by electromagnetic flowmeter
      and impedance are continuously monitored and stored on analogue tape. Cardiac
      output by thermodilution, blood oxygen (pO2) and carbon dioxide (pCO2) tensions
      are measured. ECG is converted to heart rate, mean blood pressure is integrated,
      and the high-frequency (1.50-4.00 Hz) component of the impedance signal delta Z
      is computed using autoregressive spectral estimation. Stroke volume, peripheral
      vascular resistance (PVR) and cerebral vascular resistance (CVR) are calculated.
      pCO2 and CF increase and pO2 decreases during hypoventilation. CF correlates
      positively with cardiac output, stroke volume, delta Z and pCO2, and negatively
      with pO2 and CVR. delta Z correlates positively with heart rate and cardiac
      output, and negatively with PVR and CVR. It is concluded that the impedance
      signal is related to the amount of blood transmitted to the brain by every beat
      of the heart, depending on the changes in both the systemic circulation and the
      cerebral vascular compliance.

PMID- 9538550
TI  - Exactness of source analysis of biomagnetic signals of epileptiform spikes by the
      method of spatial filtering: a computer simulation.
AB  - On the basis of spatial covariance it is found that, by spatial filtering the
      localisation of a single dipole source, both parallel and perpendicular to the
      measurement plane (assuming a signal-noise ratio of 5:1), can be performed with
      an accuracy of < 0.5 mm. When the signal-noise ratio is increased to 30:1, the
      resolution of temporally independent current sources separated by 2 mm becomes
      practicable. This resolution study is carried out by means of a pair of unity
      current dipoles with the dipole distance as a varying source model parameter. The
      conclusions, drawn from the results of computer simulation and supported by
      statistical calculations, refer to the spherical model of the volume conductor of
      the brain.

PMID- 9538551
TI  - Fetal heart modelling based on a pressure-volume relationship.
AB  - Study of the cardiovascular system of the human fetus is based on non-invasive
      measurement methods such as Doppler echography systems. The circulation
      conditions in fetal vessels are usually evaluated by resistance indices, giving
      limited physiological information on distal territories such as the placenta or
      the brain. To enhance the understanding of human fetal haemodynamics, a numerical
      model of the fetal heart has been developed, using the hydraulic-electric
      analogy. The model is based on a mechanical hypothesis of parallel functioning of
      the right and left ventricles, considered to have analogue elastance properties.
      Their behaviour is equivalent to that of a single ventricle ejecting an
      equivalent blood volume of 7 ml in the aorta. The characterisation of the
      equivalent ventricle is based on the determination of a set of four parameters
      (Emax, Vo, kv and Po) representing the maximum ventricle contractility, a
      reference volume, and volume and pressure constants, respectively. The model
      proposed is validated by studying the effects of preload and afterload variations
      on the fetal heart work, and by comparing the numerical results with literature
      and measured data. The model constitutes the first step towards a global model of
      the cardiovascular system of the human fetus.

PMID- 9538552
TI  - Computer simulation of circulation in patient with total cavo-pulmonary
      connection: inter-relationship of cardiac and vascular pressure, flow, resistance
      and capacitance.
AB  - The aim is to develop a computer model representative of the circulation in a
      patient with a uni-ventricular heart surgically palliated by a total cavo
      pulmonary connection (TCPC). The effects of known hazardous exposures on this
      type of circulation are investigated. A model of the cardiovascular system is
      built using standard components such as transmission lines, restrictors and
      capacitances. The chamber of the heart consists of a volume connected to
      checkvalves, and an oscillating source flow connected to the volume represents
      the pumping of the heart. The following are simulated: exposure to cold, heat,
      high altitude, accelerating forces, blood loss, reduction in ventricular
      function, atrioventricular-valve regurgitation and treatment with afterload
      reducing agents. During simulations, all the parameters can be changed,
      independently of each other, and the resulting changes in flow, resistance and
      pressure are recorded. Exposure to cold, reduced ventricular function and
      atriventricular-valve regurgitation result in a decrease in cardiac output (14,
      58 and 45%, respectively). At high altitude, an increase of 18% is noted in the
      central venous pressure. Afterload-reducing agents increase the cardiac output by
      8% and reduce central aortic pressure by 23%. Blood loss results in a marked
      reduction in perfusion pressure. It is concluded that the computer model is a
      useful instrument for simulation of a TCPC or Fontan circulation. The original
      criteria for this surgical procedure are those showing the most marked
      haemodynamic responses to different stimulus.

PMID- 9538553
TI  - Assessment of distributed arterial network models.
AB  - The aim of this study is to evaluate the relative importance of elastic non
      linearities, viscoelasticity and resistance vessel modelling on arterial pressure
      and flow wave contours computed with distributed arterial network models. The
      computational results of a non-linear (time-domain) and a linear (frequency
      domain) mode were compared using the same geometrical configuration and identical
      upstream and downstream boundary conditions and mechanical properties. pressures
      were computed at the ascending aorta, brachial and femoral artery. In spite of
      the identical problem definition, computational differences were found in input
      impedance modulus (max. 15-20%), systolic pressure (max. 5%) and pulse pressure
      (max. 10%). For the brachial artery, the ratio of pulse pressure to aortic pulse
      pressure was practically identical for both models (3%), whereas for the femoral
      artery higher values are found for the linear model (+10%). The aortic/brachial
      pressure transfer function indicates that pressure harmonic amplification is
      somewhat higher in the linear model for frequencies lower than 6 Hz while the
      opposite is true for higher frequencies. These computational disparities were
      attributed to conceptual model differences, such as the treatment of geometric
      tapering, rather than to elastic or convective non-linearities. Compared to the
      effect of viscoelasticity, the discrepancy between the linear and non-linear
      model is of the same importance. At peripheral locations, the correct
      representation of terminal impedance outweight the computational differences
      between the linear and non-linear models.

PMID- 9538554
TI  - Measurement of flow in infusion systems.
AB  - The development of three flow sensors for application in infusion systems is
      presented. One sensor measures the time of flight of an air bubble. A special
      design allows the bubble to be reused after every measuring cycle. The second
      flow sensor determines the pressure drop over a hydraulic bridge that is designed
      in analogy to an electrical Wheatstone bridge. The third sensor works using the
      phenomenon of heat transmission into the measuring liquid. Owing to their design,
      the sensors show different characteristics.

PMID- 9538556
TI  - Quantitative analysis of errors due to power-line interference and base-line
      drift in detection of onsets and offsets in ECG using wavelets.
AB  - Timing characterisation of the ECG using wavelet transforms is a new technique in
      which multiscale analysis reduces the influence of noise. This technique issued
      to investigate the effect of noise and to estimate the errors involved in the
      detection of onsets and offsets of ECG waves. With appropriate choice of scales
      of analysis, the study shows that the errors involved in the measurement of QRS
      width in the presence of base-line wander are negligible. The 50 Hz power-line
      interference introduces a maximum error of 6.25% if it is greater than 50% of the
      signal amplitude. The P and T complexes are not affected by power-line
      interference, but the base-line wander introduces a maximum error of 9.6%. In
      situations with the simultaneous presence of both types of noise, the use of an
      optimised scale restricts the errors to within clinically acceptable limits.

PMID- 9538555
TI  - Interstitial fluid flow in tendons or ligaments: a porous medium finite element
      simulation.
AB  - The purpose of this study is to describe interstitial fluid flow in axisymmetric
      soft connective tissue (ligaments or tendons) when they are loaded in tension.
      Soft hydrated tissue was modelled as a porous medium (using Darcy's Law), and the
      finite element method was used to solve the resulting equations governing fluid
      flow. A commercially available computer program (FiDAP) was used to create an
      axisymmetric model of a biomechanically tested rat ligament. The unknown
      variables at element nodes were pressure and velocity of the interstitial fluid
      (Newtonian and incompressible). The effect of variations in fluid viscosity and
      permeability of the solid matrix was parametrically explored. A transient loading
      state mimicking a rat ligament mechanical experiment was used in all simulations.
      The magnitude and distribution of pressure, stream lines, shear (stress) rate,
      vorticity and velocity showed regular patterns consistent with extension flow.
      Parametric changes of permeability and viscosity strongly affected fluid flow
      behaviour. When the radial permeability was 1000 times less than the axial
      permeability, shear rate and vorticity increased (approximately 5-fold). These
      effects (especially shear stress and pressure) suggested a strong interaction
      with the solid matrix. Computed levels of fluid flow suggested a possible load
      transduction mechanism for cells in the tissue.

PMID- 9538557
TI  - Two-point calibration procedure of the forced oscillation technique.
AB  - The forced oscillation technique is usually calibrated by loading the measuring
      device with a known impedance. A correction function is calculated, relating the
      measured and reference impedances at each frequency. However, this one point
      calibration procedure does not account for transducer asymmetry. A procedure has
      previously been presented to circumvent this problem: in addition to one known
      reference impedance, the calibration was repeated with the system occluded
      (infinite impedance). The aim of the present study was to evaluate a variant of
      this procedure, in which instead of resorting to an extreme condition imposing
      high requirements on the flow measuring system, two reference loads of 4 and 50
      hPal-1 s were measured, thus covering the range of impedances observed in
      children and infants (a two-point procedure). The calibration procedure was
      performed with these two impedances and evaluated with a third impedance of
      approximately 17 hPal-1 s. The results of three calibration procedures were
      compared: one-point, two-point and a previously reported calibration procedure.
      Impedances consisted of sintered glass and mesh wire screens mounted in glass or
      polyvinyl tubes. For low impedance values, in the range of 4 to 17 hPal-1 s,
      measured and predicted values were similar for the three calibration procedures
      at frequencies from 4-52 Hz, although with the one point calibration procedure
      there was some underestimation above 44 Hz. With the highest load, especially
      above 32 Hz, marked discrepancies between measured and predicted values were
      observed with the one-point calibration procedure and the previously reported
      calibration procedure. Under these circumstances the two-point procedure is
      preferred.

PMID- 9538558
TI  - Development of a portable multipurpose recorder using a 24-hour ambulatory
      recorder: application to polysomnography.
AB  - With the advance of chronobiology, demands for simultaneous long-term monitoring
      and recording of various biosignals are increasing. To meet these demands we have
      developed a portable multipurpose recording system using a 24-hour ambulatory
      recorder. This technical achievement of less restrictive round-the-clock
      simultaneous recording of biosignals from not only the circulatory system, but
      also from the neurological and digestive systems of a subject in his/her daily
      life will contribute to clinical research on circadian variations of biosignals
      and EEG analysis during sleep.

PMID- 9538559
TI  - Optimising assay sequence on automated coagulation instrumentation.
AB  - An embedded knowledge-based system has been developed to determine the optimum
      sequence for assays performed on a random access coagulation analyser. This
      knowledge base is in the form of a set of rules describing penalties associated
      with certain sequences of assays. The optimisation of assay sequences increases
      throughput and reduces consumption of cleaning solutions and generation of waste.
      A flexible design also facilitates updates to the knowledge base as assays are
      modified and added in the future.

PMID- 9538560
TI  - Vitamin A uptake cells in the endocrine organs of Japanese quails, Coturnix
      coturnix japonica.
AB  - The vitamin A uptake cells in the anterior pituitary, thyroid gland, and pancreas
      of Japanese quails, coturnix coturnix japonica, were examined by the use of Sudan
      III staining, toluidine blue staining, fluorescence microscopy and electron
      microscopy. After excess vitamin A administration, most of interstitial cells,
      corresponding to fibroblasts, increased markedly the size and number of lipid
      droplets in the cytoplasm which emitted vitamin A fluorescence intensively. The
      reactions to vitamin A administration were in parallel with the vitamin A dosage.
      In particular, the cells of the thyroid gland and pancreas were comparable to the
      Ito cells of the liver in their vitamin A uptake capacity. The present study
      demonstrates that interstitial cells either identical with or closely related to
      the Ito cells of the liver are widely distributed in the connective tissue of
      these endocrine organs. The possible physiological roles of the vitamin A uptake
      cells and also the species difference in the vitamin A uptake capacity of these
      cells are discussed.

PMID- 9538561
TI  - Beneficial effects of perfluorotributylamine/pluronic F-68 stem-emulsion (FC43se)
      on discordant lung xenografts.
AB  - The aim of this study was to assess the effectiveness of
      Perfluorotributylamine/Pluronic F-68 Stem-Emulsion (FC43se) against hyperacute
      rejection in rabbit-pig xenodiscordant transplantation in an ex-vivo lung model.
      Rabbits were divided into two groups. In Group 1 (control), after extraction, the
      lungs were connected directly to the experimental circuit as soon as possible.
      The lungs were then perfused with 100 ml of pig blood only. In Group 2 (FC(+)
      Group), after extraction, the lungs were connected to the same circuit as soon as
      possible. The lungs were then perfused with 10 ml of FC43se plus 90 ml of pig
      blood. The duration of perfusion was defined from when the perfusion started
      until the PAP reached 50 mmHg. Significant differences in survival were seen
      between Group 1 and Group 2: in Group 1, the survival time was 51.9 +/- 16.8 min,
      whereas in Group 2 the survival time was 76.9 +/- 12.4 min (p < 0.01). The wet-to
      dry weight ratio after 30 min of perfusion in Group 2 was significantly lower
      than that of Group 1 and the mean pulmonary artery pressure of Group 2 at 35, 40
      and 45 min after perfusion was significantly lower than that of Group 1.
      Histological examination revealed that FC43se suppressed the adhesion of
      leukocytes to the surfaces of endothelial cells, and also attenuated the intimal
      edematous changes accompanying leukocyte infiltration. Therefore, FC43se has a
      beneficial effect on suppressing hyperacute rejection in xenogeneic discordant
      lung transplantation.

PMID- 9538562
TI  - Treatment of tumors of the spine.
AB  - Thirty-one patients with spinal tumors underwent reconstructive surgery with our
      spinal instrumentation system (MPDS and MADS), with or without our new vertebral
      tumor prosthesis. The characteristics of the spinal tumors were analysed
      statistically and the treatment outcome was evaluated. There were 4 benign
      tumors, 6 malignant tumors, and 21 metastatic tumors. The malignant tumors
      involved the sacrum more frequently than the benign tumors (p = 0.0098).
      Metastatic tumors involved the thoracic spine more frequently than benign or
      malignant tumors (p = 0.0161). The average number of affected vertebrae was 1.2
      in the benign tumors, 1.8 in the malignant tumors, and 2.4 in the metastatic
      tumors. The metastatic tumors had a tendency to involve the anterior or middle
      part of the spine more frequently than the benign or malignant tumors
      (statistically not significant). After surgery, neurological improvement was
      noted in 8 patients, nochange in 19 patients, and impairment due to resection of
      the nerve roots in sacral tumors in 4 patients.

PMID- 9538563
TI  - A polysomnographic study on periodic limb movements in patients with restless
      legs syndrome and neuroleptic-induced akathisia.
AB  - Eighteen patients with restless legs syndrome (RLS) and 4 patients with
      neuroleptic-induced akathisia (NIA) underwent all-night polysomnographic
      recordings before and during clonazepam treatment. Ten normal control subjects
      and 4 non-akathitic psychiatric patients treated with neuroleptics underwent
      polysomnographic recordings, which were compared with those of the RLS and NIA
      patients, respectively. Daily treatment with 0.5 to 3 mg clonazepam improved
      subjective complaints of 17 out of 18 patients with RLS and all the 4 patients
      with NIA. All the 18 patients with RLS exhibited periodic limb movements (PLM) on
      the polysomnograms before treatment, but only 2 of 10 control subjects exhibited
      PLM. Three of the 4 patients with NIA exhibited PLM, but none of the 4 controls
      on neuroleptics showed PLM. Clonazepam decreased the total number of PLM per hour
      in patients of both RLS and NIA.

PMID- 9538564
TI  - Effect of 17 beta-estradiol, retinoic acid and tamoxifen upon primary and
      transplanted thyroid tumor in B6C3F1 mice fed an iodine deficient diet.
AB  - This study was aimed to establish TSH dependent, transplantable thyroid tumor
      (TT) in B6C3F1 (BCF1) mice. In addition, transplanted TT was examined for its
      growth in mice given 17 beta-estradiol (E2), retinoic acid (RA), tamoxifen (TAM),
      T3 and T4. Both sexes of BCF1 mice were observed for 12 months under IDD and
      distilled water (DW), starting at 4 weeks of age. Groups of mice received an i.p.
      injection of radioactive iodine (131I) once at a dose of 60 mu Ci/head and/or
      given 0.25 mg E2 pellet s.c. One piece of induced pituitary or thyroid tumor was
      individually dissected aseptically and s.c. grafted under the fat pad of one site
      of the neck in the same strain of mice at 5 weeks of age. All mice were
      sacrificed between 7.5 to 13.5 months after grafting the tumors depending on the
      experiments. The transplantability of both pituitary and thyroid tumor was 100%
      in IDD mice, but TT was about 50% with a combined treatment of IDD plus E2. A
      supplement of thyroid hormones of T3 or T4 in mice with IDD completely inhibited
      the growth of in situ or grafted thyroid tumors. The growth of in situ thyroid
      gland was significantly promoted by the oral administration of RA in both sexes,
      whereas the growth of transplanted TT was significantly increased by RA in the
      female, but not in the male. Oral administration of TAM proved inhibitory upon in
      in situ and transplanted TT in the male, but not in the female. Thyroid tumor
      induced by IDD could grow only in mice with IDD and was partially regulated of
      its growth by RA and TAM.

PMID- 9538565
TI  - Abdominal aorta and visceral arteries visualized by transgastric
      echocardiography: technical considerations.
AB  - Despite the necessity of information regarding the abdominal aorta and visceral
      arteries during cardiovascular surgery, there has been no intraoperative modality
      available. We examined the feasibility and limitations of transesophageal
      echocardiography (TEE) for this purpose. In 21 consecutive patients, the celiac
      artery (CEA), superior mesenteric artery (SMA), and left and right renal arteries
      (LRA, RRA) were examined with TEE, and could be visualized in 21 cases (100%), 20
      cases (95.2%), 14 cases (66.7%) and 14 cases (66.7%), respectively. Several
      attempts were needed for successfully visualizing the LRA and the RRA in 2 and 1
      case(s), respectively. Three specific manipulations of the probe were helpful for
      visualizing these vessels: 1) an appropriate counterclockwise rotation and an
      upward flexion of the probe when the transducer entered the stomach; 2) a
      stiffening of the flexible portion of the probe at the position of upward flexion
      by fixing the handle of the TEE probe when the transducer was advanced; and 3) a
      lateral flexion of the probe to provide a rotation of the image in either the
      clockwise or counterclockwise direction and to optimize the assessment of the
      blood flow velocity in the branch artery. Inferior visualization of the renal
      arteries was a limitation of this method. Two solutions for this problem were 1)
      repeated attempts at visualization and 2) an examination of the blood flow in the
      renal parenchyma with color Doppler imaging. Because of possible damage to the
      gastric wall, it is recommended that this maneuver be conducted by an experienced
      sonographer.

PMID- 9538566
TI  - Ammonia determination as an early indicator in experimental superior mesenteric
      artery occlusion.
AB  - Superior mesenteric artery occlusion (SMAO) is often fatal. An indicator which
      enables the early diagnosis of SMAO is needed. As we think putrefaction products
      must appear and increase in the blood and ascites in SMAO, changes in the
      concentrations of ammonia, one of the putrefaction products, were measured in
      this study. Thirteen adult mongrel dogs were used for the in vitro experiment.
      The jejunum, ileum, and ascending colon were resected and incubated in saline.
      Changes in ammonia concentrations in the saline were examined at various
      incubation times. In the in vivo experiment, 11 mongrel dogs comprised the SMAO
      group and another 10 mongrel dogs comprised the control group. Changes in ammonia
      concentrations in the blood and ascites were examined in both groups. In the in
      vitro experiment, ammonia concentrations in the saline bath increased in all
      samples. It was highest in the sample from around the ascending colon, and lowest
      from around the jejunum. However, at the end of experiment, this difference
      became insignificant. In the in vivo experiment, ammonia concentrations in
      samples of the blood increased early and significantly in the SMAO group,
      compared with the control group. Ammonia concentrations in samples of the ascites
      also increased significantly. The in vitro experiment showed that ammonia leaked
      from the ischemic intestines, and secondarily, a large amount of ammonia was
      produced from intestinal putrefaction. The in vivo experiment revealed that the
      ammonia level in the blood could be used as a good early indicator of acute
      mesenteric ischemia.

PMID- 9538567
TI  - Detection of Borrelia burgdorferi from ticks (Acari) in Hebei Province, China.
AB  - From May 1992 to August 1993, 1,196 ticks were collected by flagging vegetation
      and from domestic animals in Chengde, Zhangjiakou, Shijiazhuang, and Handan
      districts of Hebei Province. Of those ticks collected, 954 were Haemaphysalis
      japonicum Warburton and H. longicornis Neumann, 205 were Ixodes persulcatus
      Schulze, and 37 were Dermacentor silvarum Olenev. Four strains of Borrelia
      burgdorferi were isolated from 135 I. persulcatus collected in Weichang and
      Zhuolu counties. Three of 574 Haemaphysalis spp. (collected in Laishui, Pingshan,
      and Xinglong counties) were positive for B. burgdorferi by direct
      immunofluorescent assay. One of 24 H. japonicum and 1 of 1 I. persulcatus
      (collected in Zhuolu) were positive for B. burgdorferi by polymerase chain
      reaction. This is the 1st report of a B. burgdorferi isolation from H. japonicum.

PMID- 9538568
TI  - Chagas disease in the Amazon Basin: association of Panstrongylus geniculatus
      (Hemiptera: Reduviidae) with domestic pigs.
AB  - Just over 100 autochthonous cases of Chagas disease are reported from the
      Brazilian Amazon Basin. Panstrongylus geniculatus (Latreille) occurs throughout
      the region and is the known vector of Trypanosoma cruzi, principal zymodeme 3
      (Z3) to the armadillo Dasypus novemcinctus. In the small riverine community of
      Furo do Rio Pau Grande, pigsties adjoining houses were heavily infested with P.
      geniculatus, which repeatedly attacked local inhabitants. Palm trees in the
      immediate vicinity were also infested. T. cruzi principal zymodeme 1 (Z1) was
      isolated from P. geniculatus, domestic pigs, and opossums, but no human
      infections were detected. The threat of endemic Chagas disease to the Amazon
      Basin from either domiciliation of local silvatic triatomine species, or from
      migration of domestic vectors, demands a program of vigilance and plans of action
      to eliminate household triatomine colonies.

PMID- 9538569
TI  - Vector competence of Aedes notoscriptus (Diptera: Culicidae) for Ross River virus
      in Queensland, Australia.
AB  - Aedes notoscriptus (Skuse) mosquitoes colonized from Brisbane, Queensland,
      Australia, were fed on blood containing Ross River (RR) virus isolated from
      Brisbane, Queensland, Australia. This colony was highly susceptible to infection,
      ID50 = 10(3.2) CCID50 per mosquito, with titers in infected mosquitoes peaking 9
      d after infection. Transmission occurred between days 9 and 14, with a maximum
      rate of 13% between days 12 and 14 after infection. Considering the peridomestic
      abundance and human blood feeding habit of Ae. notoscriptus, positive
      transmission of RR virus indicates the need to consider this species more
      seriously in the context of urban RR transmission.

PMID- 9538570
TI  - Relationships between temperature and life-history parameters of Stomoxys
      calcitrans (Diptera: Muscidae).
AB  - Relationships between temperature and life history parameters were determined for
      the stable fly, Stomoxys calcitrans (L.). Median immature developmental times
      ranged from > 60 d at 15 degrees C to < 12 d at 30 degrees C, with minimum time
      at 30.6 degrees C. Egg survival decreased from 0.98 at 15 degrees C to 0.91 at 20
      degrees C, then increased to 0.98 at 35 degrees C. Larval survival ranged from
      0.83 at 20 degrees C to 0.65 at 35 degrees C, and pupal survival ranged from 0.93
      at 20 degrees C to 0.42 at 35 degrees C with maxima at 22.1 degrees C and 19.9
      degrees C for larvae and pupae, respectively. Median longevity of females and
      males were greatest at 17.3 degrees C. Time to 50% survival ranged from > 30 d at
      15 degrees C to < 6 d at 35 degrees C. Daily fecundity averaged 1.07, 8.89,
      14.88, 26.22, and 7.90 eggs per female per day at 15, 20, 25, 30, and 35 degrees
      C, respectively. Lifetime fecundity ranged from < 30 eggs per female at 15 and 35
      degrees C to > 700 eggs per female at 25 degrees C and was greatest at 25.3
      degrees C. Net reproductive rate, and the intrinsic rate of increase had maxima
      at 25.3 and 27.8 degrees C, and mean generation time was minimum at 33.4 degrees
      C. Proportional variation in the time of immature development and adult longevity
      were independent of temperature, but proportional variation in the time of
      oviposition was related inversely to temperature. Extreme temperatures appeared
      to lengthen the preoviposition period and reduce the duration of egg production.
      Relationships were compared with previous studies. Equations developed and
      presented in this article will be used to develop a temperature-dependent stable
      fly population model.

PMID- 9538571
TI  - Comparison of black fly species (Diptera: Simuliidae) on an Amerindian
      reservation with a high prevalence of fogo selvagem to neighboring disease-free
      sites in the State of Mato Grosso do Sul, Brazil. The Cooperative Group on Fogo
      Selvagem Research.
AB  - Fogo selvagem is an autoimmune blistering skin disease that principally occurs
      among rural Brazilians living in geographically clumped disease foci. Exposure to
      hematophagous black flies possibly is related to the cause of the disease. We
      compared the occurrence, proportions, and richness of simuliid species immatures
      and the biting activity of adult females within a recently discovered, high
      prevalence focus of fogo selvagem, the Limao Verde Terena Reservation, to that of
      neighboring regions with no reported cases of fogo selvagem. Nine black fly
      species were collected from 12 stream sites during 5 trips to the fogo selvagem
      focus. The species showed longitudinal (upstream-downstream) trends in
      occurrence, proportions, and richness, and the abundance of simuliid immatures
      was greater at downstream sites. The most prevalent species at the focus,
      Simulium nigrimanum (Macquart), dominated the stream sites with highly abundant
      simuliid assemblages, and was the most common black fly in human bait
      collections. This species was absent or in very low numbers in neighboring
      valleys and villages that did not have cases of fogo selvagem.

PMID- 9538572
TI  - Susceptibility of selected strains of Australian mosquitoes (Diptera: Culicidae)
      to Rift Valley fever virus.
AB  - We evaluated the ability of selected strains of the Australian mosquitoes, Aedes
      notoscriptus (Skuse), Ae. vigilax (Skuse), Culex annulirostris Skuse, and Cx.
      quinquefasciatus Say, to function as potential vectors of Rift Valley fever (RVF)
      virus, should that virus be introduced accidentally into Australia. After feeding
      on a hamster with a viremia of 10(7) plaque-forming units/ml of blood, Ae.
      notoscriptus and Cx. annulirostris were the most susceptible, with infection
      rates of 86 and 55%, respectively. Female Ae. vigilax and Cx. quinquefasciatus
      also were susceptible, with infection rates of 38 and 30%, respectively. All of
      these species transmitted RVF virus by bite 7-10 d after intrathoracic
      inoculation, and all, except Cx. quinquefastiatus (not tested), transmitted RVF
      virus 10-16 d after oral exposure. The presence of competent mosquito vectors for
      RVF virus in Australia indicates the potential for RVF virus epizootics to occur
      should this virus be introduced into Australia.

PMID- 9538573
TI  - Tick-borne borrelioses pathogen identification in Ixodes ticks (Acarina,
      Ixodidae) collected in St. Petersburg and Kaliningrad Baltic regions of Russia.
AB  - Two isolated Baltic seashore populations of Ixodes ticks were studied as vectors
      of different Borrelia genospecies in Russia by using darkfield microscopy and
      modified polymerase chain reaction (PCR). In the Kalinigrad region (Kurish Spit,
      forests near the settlements of Lesnoye and Rybachy), 788 Ixodes ricinus (L.)
      adults and nymphs were collected by flagging and studied by darkfield microscopy
      during 1995-1996. There were 88 darkfield microscopy positive specimens (11.2%)
      of which 69 were also analyzed by PCR. Borrelia afzelii and B. garinii were found
      individually and together in ticks. In this region, on the Kurish Spit, 7
      patients with tick borrelioses were observed: 2 in the Russian part of Spit and 5
      in the Lithuanian part. A significant difference was found between Borrelia
      prevalence during the spring and fall peaks of tick abundance. Specimens that
      were darkfield microscopy positive prevailed in the fall (25.15%) in comparison
      with the spring peak (7.3%). The number of specimens with identified genospecies
      prevailed in the spring: 22 out of 35 versus 4 out of 31 in the fall. Among 29
      PCR positive I. ricinus, 21 contained B. afzelii, 3 had B. garinii, and 2 had
      dual infection. In 1995, only B. afzelii infected specimens were observed. In the
      vicinity of St. Petersburg (the seashore of the northern Gulf of Finland, in
      forests near Lisy Nos, Morskaja) during 1992-1996, 31 patients with a tick-borne
      borrelioses were registered. We collected 487 Ixodes persulcatus Schulze by
      flagging and studied them by darkfield microscopy in 1995-1996 of which 144 ticks
      (29.6%) were darkfield microscopy positive. Sixty darkfield-positive specimens
      were analyzed by PCR, and in 88.3% of cases genospecies were identified. B.
      afzelii and B. garinii were identified individually and together in ticks. In
      1995, I. persulcatus with dual infection prevailed with 11 out of 21 (52.4%
      positive), whereas in 1996, most I. persulcatus ticks contained B. garinii
      (81.2%). Dual infection was observed in 4 of 32 (12.5%) ticks. Dual infections in
      I. persulcatus females increased within the seasonal peak of tick activity as was
      observed in 1995 and in 1996. Many patients not only had erythema migrans, but
      also exhibited early neurological symptoms that coincided with the number of tick
      vectors that had dual infections in June, indicating that these patients were
      bitten by female ticks that had dual infections. A significant difference existed
      between levels of infection in I. ricinus and I. persulcatus, with all 3 types of
      Borrelia infection observed 2 times more often in I. persulcatus than in I.
      ricinus and dual infection occurred in I. persulcatus 3.7 times more often. It
      appeared that I. persulcatus is a much more dangerous vector of tick-borne
      borrelioses than I. ricinus.

PMID- 9538575
TI  - Effects of fly abundance on catch index of traps for Glossina fuscipes fuscipes
      (Diptera: Glossinidae).
AB  - The effect of fly abundance on the catch index of traps and that of rain as a
      source of variation in fly abundance were investigated for Glossina fuscipes
      fuscipes Newstead around Lake Victoria, western Kenya, using odor-baited and
      color-improved traps. There was a significant inverse relationship between the
      catch index of experimental traps and abundance of flies; the catch index being
      the ratio of catch in the experimental trap per catch in a reference trap. At low
      tsetse abundance (< 10 flies per trap per day) there was a 3-fold increase of the
      catch of females in the experimental trap compared with the control. Rainfall
      alone explained 22-87% of the total variation of fly abundance. It is suggested
      that fly abundance should be considered in evaluating baits for G. f. fuscipes or
      when using traps for monitoring. The relative depression of the catch index at
      high abundance may be related to avoidance of conspecifics. Flies entered
      standard traps in an inverse proportion to the number observed at the trap.
      Females approached traps in greater numbers when fewer decoys (dead flies) were
      placed on traps.

PMID- 9538574
TI  - Dot immunobinding assay for detection of mite antigens in house-dust samples.
AB  - A new test was developed specifically to detect mite antigens in house-dust. It
      uses a nitrocellulose dipstick spotted with specific antimite antibodies that act
      as a capture matrix; the same antibodies act as a detecting reagent when
      conjugated with colloidal dye particles. Aclotest is a 1-step assay, where a
      spotted dipstick is placed in a tube containing the detecting reagent and the
      house-dust sample. No instrumentation or previous extraction procedure of the
      sample is required, and the test response is visible as a colored spot, after 1 h
      incubation. The sensitivity and specificity of the new test were compared with
      those of Acarex and Der p1/Der f1 ELISA tests.

PMID- 9538576
TI  - Comparative rearing of Wohlfahrtia magnifica (Diptera: Sarcophagidae) in dead and
      living tissues and the impact of cold storage on pupal survival.
AB  - Larvae from adults of Wohlfahrtia magnifica (Schiner) emerging from pupal cold
      storage (4 degrees C for 80-100 d) were reared in wound and dead tissues. Of
      2,150 first instars placed on a mixture of muscle + liver in a climate-controlled
      room, 47.1% molted to 2nd instar, 6.1% to 3rd instar, and 4.6% pupated. Two
      females emerged from these pupae after 14 d. To synchronize adult emergence, 191
      pupae that were reared in living or dead tissues and were 2, 8, and 11 d old were
      cold-stored in lots according to age. Adult emergence was greatest in pupae of 2
      d-old (57.1%) and, pupae developing in living and dead tissues, 22.5 and 8.7%,
      respectively. When the experiment was repeated with cold-stored pupae from 0 to
      11 d old, developing in living tissues, the highest emergence was again in 2-d
      old pupae (55.0%). These data have important implications for the control of
      adult emergence which may be used in further biological studies.

PMID- 9538577
TI  - Effects of larval nutrition, adult body size, and adult temperature on the
      ability of Anopheles gambiae (Diptera: Culicidae) to melanize sephadex beads.
AB  - A Plasmodium-refractory strain (L35) of the mosquito Anopheles gambiae Giles
      melanizes late ookinetes on the basal surface of the midgut, resulting in the
      death of the parasites. This strain also melanizes CM C-25 Sephadex beads, which
      serve as a model system for investigating the melanization response. The effects
      of larval nutrition, adult body size, and temperature of the adult environment on
      the ability of refractory females to melanize CM C-25 beads were studied.
      Nutritional deprivation during the larval stages significantly decreased the
      ability of adults to melanize beads. In addition, bead melanization decreased
      progressively as the environmental temperature of the adults increased from 24 to
      30 degrees C. We conclude that environmental stress may affect the immune
      responses of An. gambiae.

PMID- 9538578
TI  - Serum composition of Aedes aegypti (Diptera: Culicidae) larvae and the production
      of an oviposition repellent are influenced by infection with the entomopathogenic
      digenean Plagiorchis elegans (Trematoda: Plagiorchiidae), starvation, and
      crowding.
AB  - Subjecting Aedes aegypti (L.) larvae to conditions that induced the production of
      oviposition repellency also reduced their wet and dry weights and the
      concentration of total serum carbohydrates, amino acids, and proteins. Thus,
      infection with metacercariae of the entomopathogenic digenean Plagiorchis elegans
      (Rudolphi), starvation for 7 d, or crowding for 2 d reduced larval dry weights by
      as much as 32, 20, and 23%, respectively, and wet weights by 20, 14, and 11%,
      respectively. Total serum carbohydrates declined by as much as 36, 21, and 29%
      for infected, starved, and crowded larvae, respectively, amino acids by 39, 48,
      and 44%, and protein concentrations by 72, 63, and 62%, respectively. Repellency
      dilution titers were correlated inversely with movement of the mouth parts and
      gut. Incubation of infected, starved, and crowded larvae in 0.01 g/liter glucose
      greatly reduced the level of repellency of their waters, whereas adding glucose
      to repellent waters had only minor effects. Results indicate that the induction
      of repellency is associated strongly with nutritional depletion effects.

PMID- 9538579
TI  - Genetic variability among populations of the sand fly Lutzomyia (Lutzomyia)
      longipalpis (Diptera: Psychodidae) from Central America.
AB  - Eleven Central American populations of Lutzomyia longipalpis (Lutz & Neiva) were
      analyzed for genetic variation at 16 enzyme loci. The aim was to study the
      genetic structure among populations within this region and to identify demes that
      may represent different sibling species. Genotypic frequencies within populations
      agreed with Hardy-Weinberg expectations, indicating that there were no sympatric
      sibling species among these 11 populations. Levels of genetic distance between
      pairs of populations were very low (< 0.02). Some substructing was evident,
      because after genotypes of all populations mere pooled, 7 of the 16 enzyme loci
      deviated from Hardy-Weinberg expectations. Estimates of effective migration rates
      among populations (Nm) were low (3.7), indicating that gene flow was restricted.
      These data explained observed genetic substructuring when all genotypes were
      pooled.

PMID- 9538580
TI  - Onset of resistance to fenvalerate, a pyrethroid insecticide in Argentine horn
      flies (Diptera: Muscidae).
AB  - Haematobia irritans (L.) horn flies recently have immigrated into Argentina from
      Brazil or Paraguay. Bioassays were conducted with fenvalerate to develop baseline
      information on pyrethroid susceptibility. Four populations tested in 1994 and
      1995 were more susceptible than a laboratory strain of horn fly not exposed to
      insecticides since 1970, but 3 populations from Corrientes Province tested in
      1996 were moderately resistant to fenvalerate, with resistance ratios ranging
      from 3 to 26. Argentine horn fly populations were exposed to pyrethroid
      treatments of pour-on, spray, and dip formulations for 4 yr before developing
      resistance. Horn flies in the United States developed pyrethroid resistance after
      2 yr of treatment with pyrethroid ear tags.

PMID- 9538581
TI  - Laboratory life cycle of Ixodes woodi (Acari: Ixodidae).
AB  - A 24-mo study of the laboratory life cycle of the tick Ixodes woodi Bishopp was
      conducted. No other such study of any species in the subgenus Ixodiopsis
      Filippova has been reported. Three generations of I. woodi were examined. Larvae
      and nymphs fed for an average of 4 d; approximately 8-9 d were required for
      females to engorge. Females laid approximately 900 eggs that required an average
      of 37.33 d to hatch.

PMID- 9538582
TI  - Ehrlichial DNA amplified from Ixodes ricinus (Acari: Ixodidae) in France.
AB  - Granulocytic ehrlichia 16S rDNA was amplified for the 1st time from an Ixodes
      ricinus (Linne) tick collected in Europe. Sequence analysis of polymerase chain
      reaction products from the 16S rRNA gene demonstrated the organism from which it
      originated to be closely related to the agent of human granulocytic ehrlichiosis,
      an emerging disease that was recently described in the United States; Ehrlichia
      phagocytophila, the agent of tick-borne fever of ruminants in Europe; and
      Ehrlichia equi. the agent of the worldwide equine granulocytic ehrlichiosis.
      These granulocytic ehrlichiae have been associated with Ixodes spp. ticks that
      may act as vectors. It remains to be determined if each of these granulocytic
      ehrlichiae, that may constitute variants of the same species, is responsible for
      a specific disease in animals and in humans.

PMID- 9538584
TI  - Measurement concerns when using existing data bases.

PMID- 9538583
TI  - Sex specific proteins and proteases present in the midguts of Anopheles albimanus
      (Diptera: Culicidae).
AB  - Proteins and proteases present in midgut tissues of sugar-fed Anopheles albimanus
      (Wiedemann) males and females were studied by 2-dimensional electrophoresis and
      zymograms using gelatin and hemoglobin as substrates. Protein patterns differed
      between sexes. Some proteins were similar in both sexes, but differed in
      intensity. Sex specific proteins and midgut proteases also were detected. These
      findings indicate the possibility of sex dependent regulation of midgut proteins
      and protease production.

PMID- 9538586
TI  - A reliability and validity study of the Women's Role Strain Inventory.
AB  - The purpose of this study was to theoretically conceptualize, develop and test
      the Women's Role Strain Inventory (WRSI) which assesses role strain in women who
      have multiple roles. There is limited research published related to role strain
      of women, although role strain, role conflict and role stress have been
      documented to have negative and positive effects (Hall 1975, Hall 1992). The
      theoretical basis for this study is based upon Goode's Theory of Role Strain
      (1960) and Sieber's Theory of Role Accumulation (1974). The pilot consisted of 62
      female nurses, and the sample used for construct validity consisted of 445 female
      nurses. Content validity resulted in a content validity index of (.91).
      Exploratory factor analysis with varimax rotation resulted in a three-factor
      solution supporting Goode's (1960) theory of role strain, and Sieber's (1974)
      theory of role accumulation. Alpha coefficients for the three subscales were .89
      (role distress), .86 (role enhancement), and .81 (role support). Internal
      consistency of .93 was achieved for the overall WRSI. Test-retest coefficients
      ranged from .61 to .91. The high reliability and validity of the WRSI make it a
      reliable and valid instrument to measure role strain of women.

PMID- 9538585
TI  - An expanded neonatal morbidity scale for premature infants.
AB  - We revised a neonatal morbidity scale (the NMS) that has served as a means for
      comparison of neonatal illness in studies of high-risk neonates after initial
      hospital discharge. With an inception cohort approach, 89 premature infants at an
      urban university hospital were studied with the expanded scale (the ENMS). The
      original scale, published in 1983, was reworked and expanded based on advances in
      the diagnosis and management of neonates. A social risk scale was added. Linear
      and logistic regression analyses were used to judge validity of the newly revised
      scale and to examine its predictive ability for outcomes at six months of age.
      Concurrent validity was supported by the relationship between the ENMS-SRS and:
      birthweight (R2 = .54), gestational age (R2 = .50), length of stay (R2 = .47).
      Inter-rater reliability was .95. The ENMS, embodying a contemporary patient
      profile, is valid for a population of premature infants in a U.S. urban setting
      and has predictive validity for a few outcomes within six months of discharge
      from a special care unit.

PMID- 9538587
TI  - Psychometric evaluation of the Russian Language version of the Resilience Scale.
AB  - The Resilience Scale (RS) was developed by Wagnild and Young (1993) to measure a
      personality characteristic or coping resource that facilitates adaptation. The
      RS, however, has not been evaluated with foreign-born populations. Therefore, the
      purpose of this study was to report the factor structure, internal consistency,
      and concurrent validity of a Russian language version of the RS in a sample of
      450 recent former Soviet immigrants. The 25-item 2-factor solution obtained by
      Wagnild and Young (1993) was not supported by the Russian data. However, a
      modified 12-item Russian language version of the RS was, for the most part,
      reliable and valid: The standardized factor loadings and goodness of fit indices
      obtained from confirmatory factor analysis were acceptable, the internal
      consistency of one of the two subscales was very good, and the correlations
      between scores from the RS subscales and various measures of constructs that are
      theoretically linked with adaptation were in the expected direction and
      statistically significant.

PMID- 9538588
TI  - Organizational culture in hospitals: issues in measurement.
AB  - It is still not clear that organizational culture in hospitals is linked to
      patient or provider outcomes. However, measurement of organizational culture in
      nursing units within hospitals and for entire hospitals is common. Two
      instruments frequently used to measure hospital culture or work group culture
      within hospitals are the Organizational Culture Inventory (OCI) (Cooke &
      Lafferty, 1987) and the Nursing Unit Cultural Assessment Tool (NUCAT-2) (Coeling
      & Simms, 1993a). The purpose of this paper is to review selected empirical
      studies of organizational and work group culture in hospitals and critique these
      two measurement instruments. The paper discusses the issues of unit of
      analysis/aggregation bias and sample size when using these two instruments. It
      was concluded that OCI has been widely used in many types of organizations and
      has substantial data supporting the reliability and validity. However, the
      instrument does not always capture variation in nursing units. The NUCAT-2 has
      less reliability and validity data but researchers have reported wide variation
      among units. Individual items can be selected for use from the NUCAT-2 and it is
      less expensive to use than the OCI.

PMID- 9538589
TI  - Control over nursing practice: a construct coming of age.
AB  - The purpose of this study was to assess the psychometric properties of the
      Control Over Nursing Practice Scales using data from registered nurses (N = 1117)
      employed in four acute care hospitals in the Midwest. Psychometric evaluation
      included dimensional analysis, reliability estimation, and validity assessment of
      six dimensions of a 33-item instrument: responsibility and influence of head
      nurses, staff nurses, and committees; access to ideas; use of personal resources;
      and research utilization. Factor analysis reproduced six dimensions that
      explained 61% of the variance. Coefficient alphas ranged from .75-.89.
      Correlations between Control Over Nursing Practice with autonomy, group cohesion,
      job stress, and job satisfaction supported construct validity. Empirical testing
      of known group differences to obtain new information about the construct revealed
      that critical care nurses scored higher on research utilization than medical
      surgical or obstetrical nurses; baccalaureate-prepared nurses scored higher than
      associate or diploma nurses on responsibility and influence: committees. Contrary
      to our hypothesis, there were no differences between part-time and full-time
      nurses on any of the six dimensions.

PMID- 9538590
TI  - The Depressive Cognition Scale: further psychometric evaluation.
AB  - Depressive cognitions often precede the development of affective and behavioral
      symptoms of depression. Cognitive factors have been shown to influence the
      development of depression in older adults and thus identification of depressive
      cognitions is important for prevention of clinical depression and early
      intervention. The Depressive Cognition Scale (DCS) assesses cognitions that may
      precipitate clinical depression, and it has been found to be internally
      consistent and to demonstrate construct validity with measures of psychosocial
      development. This psychometric investigation was designed to further examine the
      construct validity of the DCS through comparison with measures of hypothetically
      related constructs. An alpha of .78 indicated acceptable internal consistency.
      Construct validity was demonstrated by significant correlations with measures of
      depression, resourcefulness, adaptive functioning, and life satisfaction. The
      study, conducted with 160 healthy elders, provides additional support for the
      reliability and validity of the DCS and yields promising evidence of its
      usefulness with elderly persons.

PMID- 9538591
TI  - Catheter-directed thrombolysis for deep venous thrombosis.

PMID- 9538592
TI  - Renal cell carcinoma in native kidneys of patients with end stage renal disease.
AB  - OBJECTIVE: To determine prevalence of renal cell carcinoma in a cohort of
      patients with end stage renal disease who underwent nephrectomies for suspicious
      cysts or masses. METHODS: A retrospective review of patients with end stage renal
      disease who were receiving hemodialysis and underwent nephrectomies were
      identified and those charts were reviewed. RESULTS: Twenty patients, from a total
      of 400 patients with end stage renal disease, had nephrectomies preformed for
      various reasons. Of these twenty patients, four were found to have renal cell
      carcinoma with an occurrence rate of 5% in these patients. At followup from 1-9
      years, all patients are alive without evidence of disease. CONCLUSIONS: Patients
      with end stage renal disease have an increased prevalence of renal cell
      carcinoma. While the patients in this series have a 100% survival at 1-9 year
      follow-up, the overall survival rate in published reports is 35%. The need is to
      identify patients at high risk for the development of this disease and perform
      annual screening.

PMID- 9538593
TI  - Nationalizing health insurance.

PMID- 9538594
TI  - Timely filing of death certificates.

PMID- 9538596
TI  - Birth and death certification: MSDH explains terms.

PMID- 9538595
TI  - Dystonia in Mississippi--educating our physicians.

PMID- 9538597
TI  - The long term effects of breastfeeding: a role for the cells in breast milk?

PMID- 9538598
TI  - Adding alpha-amylase to weaning food to increase dietary intake in children. A
      randomized controlled trial.
AB  - The addition of alpha-amylase to a food supplement for weaning-age children was
      proposed as an alternative to traditionally prepared Amylase-Rich Foods (ARF) for
      reducing the dietary bulk of weaning diets. In a self-controlled clinical trial
      including 30 healthy children, aged 10-24 months, the effect of the addition of
      alpha-amylase and extra cereal to a diet including three meals, was determined in
      terms of dietary intake. A mean increased intake of 23.8 per cent in energy and
      10.4 per cent in protein was found. The addition of commercial alpha-amylase to
      maize-based weaning foods is a useful method of increasing the nutritional value
      of weaning diets.

PMID- 9538599
TI  - Susceptibility pattern of Streptococcus pneumoniae among pre-school children in
      Kota Bharu, Malaysia.
AB  - Streptococcus pneumoniae (S. pneumoniae) is the most common bacterial cause of
      pneumonia, meningitis, and otitis media, with the highest incidence among young
      children and the elderly. S. pneumoniae was once routinely susceptible to
      penicillin, but since the mid-1980s the incidence of resistance to penicillin and
      other antimicrobial agents has been increasing all over the world. To optimize
      empirical regimens and initial therapy for S. pneumoniae infections, clinical
      healthcare providers must be informed about the prevalence and pattern of drug
      resistance among the isolates in their communities. No such data are available
      for the Malaysian population. Therefore, this study was designed to determine the
      antibiotic susceptibility pattern of S. pneumoniae among colonized pre-school
      children in Kota Bharu, Malaysia. Pharyngeal swabs were collected from children 1
      month to 6 years of age. S. pneumoniae isolates were identified according to the
      standard and tested for penicillin resistance with a 1-microgram oxacillin disk
      by the Kirby-Bauer disk diffusion methods. Of 355 nasopharyngeal specimens
      obtained from kindergarten students, in-patients and pediatric clinics over a
      period of 1 year, S. pneumoniae was isolated from 36 (10 per cent). All isolates,
      except one, were susceptible to penicillin. The resistant isolates was
      susceptible to erythromycin, chloramphenicol and cephalosporins.

PMID- 9538600
TI  - Liquid crystal thermometry for the detection of neonatal hypothermia in Nepal.
AB  - We assessed the sensitivity, specificity and likelihood ratio of a low cost
      liquid crystal strip thermometer (LCT) compared with axillary mercury thermometry
      for the detection of neonatal hypothermia in Nepal. The subjects were 76 healthy
      newborns in the government maternity hospital of Kathmandu, Nepal in winter. The
      validity of LCT for the detection of neonatal hypothermia (less than 36 degrees
      C) showed a sensitivity of 83 per cent, specificity 96 per cent, positive
      predictive value 98 per cent and a likelihood ratio of 23. Use of LCT on newborns
      in this setting raises a measured pretest probability of first day hypothermia of
      63 per cent to a post-test probability of 97 per cent. Liquid crystal thermometry
      is a simple, low-cost, and valid method for identifying core hypothermia in
      newborns. It is ideal for isolated rural communities where LCT strips could be
      added to delivery kits.

PMID- 9538601
TI  - The importance of clinical symptoms and signs in the diagnosis of community
      acquired pneumonia.
AB  - A sample of 153 children was drawn from a teaching hospital in Sao Paulo, Brazil.
      It comprised 51 pneumonia cases and equal number of non-respiratory and healthy
      controls matched by age and sex. Age ranged from 1 month to 7 years. They were
      all submitted to a standard protocol to investigate clinical symptoms and signs,
      and diagnosis of pneumonia was supported by X-ray images. Univariate data
      analysis contrasting pneumonia and non-pneumonia subjects suggested that the best
      pneumonia indicators would be chest auscultation, history of breathlessness,
      history of cough, chest in-drawing and fast respiratory rate, in descending
      order. A multivariate approach including also data from X-ray investigation was
      then tried with the application of multiple discriminant analysis to study the
      separation of pneumonia cases, non-respiratory patients and healthy children. It
      revealed that when many items of information are considered the performance of
      individual symptoms and signs change. The best predictors of pneumonia were then
      identified as chest in-drawing, chest auscultation, X-ray, history of
      breathlessness and toxaemia. Clinical symptoms taken all together contribute more
      than signs and equal X-ray in importance. Accordingly, it is concluded that any
      attention to X-ray should be secondary to clinical investigation, and it is
      suggested that the WHO's guidelines could profit with the inclusion of at least
      one clinical symptom, namely history of breathlessness which was found more
      useful than the WHO recommended breath count.

PMID- 9538602
TI  - Neonatal nutritional assessment by a method independent of precise maturity
      determination.
AB  - Data from a previous study were analysed to develop a new model for neonatal
      nutritional evaluation which is independent of precise maturity determination.
      Birth weights and arm/head ratios were recorded for each infant recruited for the
      study. Both indices were correlated by simple regression analysis with
      gestational age as the independent variable. Birth weight showed highly
      significant correlation with gestational age (r = 0.77; P < 0.001). Arm/head
      ratio was also correlated with birth weight with highly significant correlation
      coefficient (r = 0.81; P < 0.001). The regression line of arm/head ratio on birth
      weight, with the demarcated 95 per cent confidence spread, formed the new model
      for neonatal nutritional assessment. The model had a sensitivity of 80.54 per
      cent and specificity of 90.22 per cent using nutritional status determined by
      clinical features as reference. Since the model is independent of precise
      maturity determination, which limits the potential usefulness of several methods
      of neonatal nutritional assessment, it is recommended as a rapid, simple, and
      reliable appropriate health technology for developing communities.

PMID- 9538603
TI  - Decreased polyunsaturated fatty acids in sickle cell anaemia.
AB  - The purpose of this study was to determine if the growth retardation often
      associated with sickle cell anaemia could be related in part to a deficiency of
      essential fatty acids. We reported recently that children with sickle cell
      disease in Jos, Nigeria have lower levels of serum amino acids and higher levels
      of urinary amino acids than their healthy counterparts. In the current study, we
      determined that the serum phospholipids of children with sickle cell anaemia did
      not deviate in the proportions of the essential fatty acids, linoleic and alpha
      linolenic they contain compared to controls. However, their serum phospholipid
      profiles were significantly different in the proportions of four other fatty
      acids. Specifically, the phospholipids of children with sickle cell anaemia
      contained 19 per cent more palmitic acid (P = 0.006), 22 per cent more oleic acid
      (P = 0.014), 18 per cent less arachidonic acid (P = 0.008), 51 per cent less
      eicosapentaenoic acid (P = 0.0008), and 43 per cent less decosahexaenoic acid (P
      = 0.001). These data show that children with sickle cell anaemia are not
      deficient in essential fatty acids, but that the fatty acid elongation and
      desaturation pathway is somehow disturbed in this disease.

PMID- 9538604
TI  - Cystic fibrosis in bahrain incidence, phenotype, and outcome.
AB  - To identify the incidence and evaluate the causes of high mortality among
      Bahraini children with cystic fibrosis, we studied, retrospectively, 25 patients
      diagnosed as proven cases of cystic fibrosis at Sulmaniya Medical Center, the
      main referral center on the island, from January 1978 to December 1995. With
      extrapolation of the study data to the general population, the incidence of
      cystic fibrosis in Bahrain is at least one in 5800 and the prevalence is at least
      3 in 100,000 population. Consanguineous marriage is documented in 80 per cent of
      the cases. Cystic fibrosis in Bahraini children is phenotypically severe, this is
      inferred from early age of presentation (mean of 2 months +/- 1 month) and early
      age of diagnosis (mean 4 +/- 1 month), development of pancreatic insufficiency by
      1 year of age in all of the study patients, failure to thrive in 96 per cent of
      the patients, hypoalbuminemia in 48 per cent, meconium ileus in 20 per cent,
      progressive lung disease in 84 per cent at an early age, and early colonization
      with Pseudomonas aeruginosa. Age-specific mortality in the first year of life
      showed dramatic decline from 80 per cent between 1981 and 1985 to 50 per cent
      from 1986 to 1990, and to 9 per cent from 1991 to 1995. This improvement in
      survival is believed to be due to increased awareness among medical professionals
      and improved treatment.

PMID- 9538605
TI  - Diagnosis of tuberculosis: PPD or BCG test.
AB  - In recent years, several articles have been published about BCG tests in the
      diagnosis of tuberculosis, particularly in children. The test is reportedly more
      sensitive and more specific than tuberculin test (PPD). We evaluated the results
      of simultaneous application of PPD and BCG test in order to assess its efficacy
      in adults and adolescents with tuberculosis (tbc). We applied BCG test and PPD
      concurrently in 35 healthy controls and 41 tuberculosis cases presented to
      Research Hospital, Inonu University and Malatya Tuberculosis Dispensary with
      clinical and radiological findings. The subjects also had sputum examined for
      presence of acid-fast bacilli (AFB) by direct microscopy, culture on Lowenstein
      Jensen medium and by polymerase chain reaction (PCR). We conclude that BCG test
      is more sensitive and more specific than PPD in diagnosis of tuberculosis in
      adults and adolescents.

PMID- 9538606
TI  - External hydrocephalus: a report of 16 cases from Oman.
AB  - Sixteen cases of external hydrocephalus (EH) were seen from January 1993 to June
      1995. There were 13 (81 per cent) male and three female children. Fourteen (88
      per cent) were under 12 months of age. Three siblings with EH were seen in one
      family. All, but three recovered over time without medical or surgical
      intervention. These three needed cerebral decongestants in the acute phase. This
      is the first report of EH from Oman.

PMID- 9538607
TI  - Endothelin-1 levels in mothers with eclampsia--pre-eclampsia and their newborns.
AB  - We examined concentrations of endothelin-1 in fetal and maternal plasma samples
      during hypertensive and normotensive pregnancies. There were significant
      differences between endothelin-1 levels of eclamptic-preeclamptic mothers'
      newborns and healthy preterm infants (P < 0.001), but there was no significant
      difference between endothelin-1 levels of healthy term and preterm infants (P >
      0.05).

PMID- 9538608
TI  - Plasma fibronectin levels and age-corrected birth weight in hypertensive
      normotensive mothers and their newborns.
AB  - Serum fibronectin levels were measured in 63 mothers including 16 healthy
      normotensive pregnant women, 17 eclamptic women, 16 pre-eclamptic women, and 14
      chronic hypertensive patients; as well as their term newborns. There was negative
      correlation between age-corrected birth weight and mothers' fibronectin levels in
      the eclamptic and preeclamptic groups, but no significant correlation in the
      chronic hypertensive group and healthy pregnant women.

PMID- 9538609
TI  - Breastfeeding and bloody diarrhoea in young children.

PMID- 9538610
TI  - Haemostatic status of children with protein-energy malnutrition.

PMID- 9538611
TI  - Effect of storage temperature on microbial quality of infant milk.

PMID- 9538613
TI  - Meningitis in home delivered neonates in Pondicherry, South India.

PMID- 9538612
TI  - The seroprevalence of anti-HAV among 0-16-year-olds referred to pediatric
      outpatients clinics of a hospital.

PMID- 9538614
TI  - Gestational age assessment in preterm neonates weighing less than 2500 grams.

PMID- 9538615
TI  - Parents' management of ARI in the Region of Marrakech.

PMID- 9538616
TI  - Ultrastructural localization of enzymes in biomembranes as revealed by new enzyme
      cytochemical techniques.
AB  - In this mini-review, we describe new enzyme cytochemical methodology combined
      with cryotechniques, which we have developed in order to reveal the
      ultrastructural localization of enzymes in biological membranes. This combined
      approach has been shown to be a valuable tool to study topology, dynamics, and
      function of enzymes in a more lifelike state.

PMID- 9538617
TI  - Case report: a rare congenital esophageal malformation on double esophagus in the
      rat.
AB  - A double esophagus was coincidently observed in one male rat among a group of
      Wistar adult rats used for histological studies. This is apparently the first
      case reported in the rat and other animals.

PMID- 9538618
TI  - Variations of abductor pollicis longus and extensor pollicis brevis muscles:
      surgical significance.
AB  - To investigate variations of the abductor pollicis longus and the extensor
      pollicis brevis muscles, an anatomic study was performed on 15 cadaver forearms.
      Some variations were observed as reported in previous studies. An unusual
      insertion of the abductor pollicis longus muscle and the extensor pollicis brevis
      muscle also was encountered during the dissection. Both tendons of these muscles
      were found to have inserted into the inferior side of the base of the first
      metcarpal bone together, instead of dorsal side. Our study suggested that the
      extensor pollicis brevis muscle and the abductor pollicis longus muscle
      differentiate from a common muscle.

PMID- 9538619
TI  - Determination of accuracy of quantitative immunohistochemical results with an
      antigen-immobilized filter model system.
AB  - To determine accuracy of quantitative immunohistochemical results, serially
      diluted liver cell lysates from methylcholanthrene (MC)-treated rats containing
      cytochrome P-450 (P-450) 1A were immobilized on nitrocellulose (NC) filters and
      stained by the indirect immunoperoxidase method under saturation conditions. The
      stained filters were processed for image analysis and the relationship between
      the resulting immunostaining intensity due to P-450 1A and the antigen amount
      immobilized on the filters was examined. The relationship examined in the filters
      fitted with an exponential curve. Thus, the intensity due to P-450 1A is not
      simply proportional to the antigen amount. Subsequently, immunostaining intensity
      due to P-450 1A was measured in sections from control and methylcholanthrene (MC)
      treated rats by image analysis with an image processor, and the antigen content
      in cell lysates from control and MC-treated animals was measured immunochemically
      by quantitative single radial immunodiffusion. Although immunochemically measured
      P-450 1A content in the lysates increased markedly (26 times), average staining
      intensity in sections increased slightly (2-3 times) after MC injection. However,
      when the exponential curve obtained from the filter binding assay was used as a
      standard curve to convert staining intensity in sections to molar content of P
      450 1A, the resulting content was compatible with the immunochemical content. The
      divergence between the increase in immunochemically measured P-450 1A content and
      that in immunostaining intensity in sections after MC injection is therefore
      attributed primarily to the curvilinear relationship between the intensity and
      the content.

PMID- 9538620
TI  - Estimation of age from the femur of Japanese cadavers.
AB  - This study was designed to estimate the age at the death of cadavers by
      histomorphometry of the femur. Samples from 72 Japanese males from 43 days to 92
      years old and 26 females from 2 to 88 years old were used. The thickness of
      sections was adjusted to 50-70 microns by grinding with sandpaper. The sections
      were not any decalcified. They were stained with Villanueva's bone staining
      powder and thionin dye. The microradiographs of the sections were obtained by a
      soft x-ray apparatus. The area, length, width, and perimeter of the perfect
      osteon and haversian canal were measured. The type II osteon number, osteon
      fragment number, and area of triangle were also determined. These parameters were
      examined by an image analyzer. The parameters of the osteon showed a high
      correlation coefficient with age (magnitude of r > or = 0.77), whereas those of
      the haversian canal were low (magnitude of r < or = 0.11). All parameters were
      subjected to multiple regression analysis for producing a multiple regression
      equation of age estimation. For the stepwise selection method, the perimeter of
      osteon, length of the haversian canal, and osteon fragment number were selected
      for the equation. Their multiple r2 and standard error of estimation were 0.8874
      and 6.39, respectively. For the forward selection method, in addition to the
      above items, three parameters, the length of osteon, area of triangle, and width
      of osteon, were selected. Their multiple r2 and standard error of estimation were
      0.9484 and 4.884, respectively. Bone staining was useful to clarify the
      demarcation between osteon and fragment, leading to increased accuracy of age
      estimation. However, precisely estimating age for the entire range from birth to
      90 years was difficult.

PMID- 9538621
TI  - [A case of the double mitral valve orifices].
AB  - In 1996 student course of gross anatomy dissection at Iwate Medical University
      School of Medicine, a case of the double mitral valve orifices was found in a
      heart of a 73-year-old male cadaver who died of acute pneumonia. No other
      congenital anomalies were detected in this heart. There was no prior history of
      heart disease. The left atrioventricular ostium was an oval with a long axis of 4
      cm and a short axis of 2.5 cm. There were double mitral valve orifices, main and
      accessory (Fig. 1). The main orifice situated left ventrally with a long axis of
      2.5 cm and a short axis of 1.7 cm, had a larger cleft. The accessory orifice
      situated right dorsally with a long axis of 2.5 cm and a short axis of 1.2 cm,
      had a smaller cleft. There was a bridge-like valvular leaflet between the two
      clefts (Fig. 1). Disregarding small incisions, both the main and the accessory
      mitral valves had two cusps, anterior and posterior. The anterior and posterior
      cusps of the main and accessory valves were continuous and considered to be
      homologous with the anterior and posterior cusps of the normal mitral valve. In
      other wards, this double mitral valve orifices was appeared to be formed by
      bridging the cleft between the anterior and posterior cusps of the normal mitral
      valve. The valvular cusps of the main or the accessory mitral valve had proper
      chordae tendineae and papillary muscles. The papillary muscles were classified
      into four groups, anterior (A), anterolateral (AL), posterior (P) and
      posterolateral (PL) according to Taniya (1974). The anterior papillary muscles
      group had a base at the anterior wall of the left ventricle, the anterolateral
      papillary muscles group had at the whole lateral wall, the posterior papillary
      muscles group had at the boundary between the interventricular septum and the
      posterior wall, and the posterolateral papillary muscles group had at the
      posterior part of the lateral wall (Fig. 3). The anterior and anterolateral
      papillary muscles groups, and the posterior and posterolateral papillary muscles
      groups of Taniya (1974) constituted the anterior and the posterior papillary
      muscles respectively in the general use of the anatomical term. The chordae
      tendineae attached to the cusps of the main orifice arose from the anterior,
      anterolateral and posterior papillary muscles groups (Fig. 2a). And those
      attached to the cusps of the accessory orifice arose from the posterolateral
      papillary muscles group (Fig. 2b). The chordae tendineae were also classified
      into three types after Taniya (1974). The A type chordae tendineae were thick and
      attached to the base of the cusps, the type B were moderately thick and attached
      to the midway between the base and the margin of the cusps, and the C type were
      thin and attached to the margin of the cusps. The main mitral valve had 6 type A,
      8 type B and 40 type C chordae. The accessory mitral valve had 0, 6 and 30
      chordae respectively (Fig. 2). This case of the double mitral valve orifices is
      considered to be included in the central type of Cascos et al. (1967) and the
      bridge type of Elfenbein et al. (1967). A morphogenetic mechanism of this type of
      the double mitral valve orifices is explained by an abnormal adhesion between the
      dorsal endocardial cushion and the left lateral endocardial cushion like mass in
      early developmental stage according to Wimsatt and Lewis (1948). But a
      possibility of an abnormal orifice in the posterior cusp which is produced in the
      process of formation of cusps, chordae tendineae and papillary muscles in later
      stage, still remains to be discussed.

PMID- 9538622
TI  - An anatomical study of the first extensor compartment of the wrist.
AB  - Anatomical variations of the first extensor compartment of the wrist are
      important during surgical operations of the wrist with de Quervain's disease. We
      studied 41 wrists from cadavers (16 whole cadavers and nine forearms) and the
      wrists of twenty-eight patients with de Quervain's disease to determine the
      variations of tendons and septa in the first extensor compartment. In 85.4
      percent of the wrists from cadavers, the number of the tendons differed from the
      standard. There was septation in 9.75 percent of the dissected wrists. These
      anatomic variations are discussed for de Quervain's disease. In twenty-eight
      patients with de Quervain's disease, septation was found in thirteen patients
      (46.43%). In 82.14 percent of the wrists from the patients, the number of tendons
      in the first extensor compartment was more than two.

PMID- 9538623
TI  - Gonadotropin-releasing hormone (GnRH) innervation of the pituitary in a cichlid
      fish, Oreochromis niloticus: a brain lesion study.
AB  - In most vertebrates, multiple gonadotropin-releasing hormone (GnRH) neuronal
      groups have been reported. In tilapia three GnRH neuronal groups (terminal nerve,
      preoptic, midbrain) have been reported. Which of the three GnRH cell groups
      regulate the pituitary is not well known. We performed brain lesions of each
      neuronal group and studied immunocytochemically the changes of GnRH fiber
      distribution in the pituitary. Lesions of the preoptic cell group resulted in
      almost complete absence of GnRH fibers in the neurohypophysis of the proximal
      pars distalis. After lesions of the terminal nerve GnRH cell group, no changes
      were observed in the distribution of GnRH fibers in the pituitary. Lesions of the
      midbrain cell group were unsuccessful because of high mortality. The present
      study indicates that the preoptic GnRH cell group is the main contributor of the
      pituitary innervation.

PMID- 9538624
TI  - Effects of prostaglandins on ethanol damage in primary cultured rat hepatocytes.
AB  - OBJECTIVES: Several reports demonstrated that ethanol administration impairs the
      DNA synthesis in rat hepatocytes. Also, it has been demonstrated that
      prostaglandin (PG) helps prevent membrane damage by hepatotoxic chemicals. In
      this study, the authors examined PG's effects on the toxicity of ethanol in the
      primary culture of rat regenerations. METHODS: We examined two kinds of
      parameters, i.e., DNA synthesis and lipid peroxidation in the primary culture of
      rat hepatocytes. Hepatocytes were isolated by the collagenase perfusion method.
      The rate of DNA synthesis was determined by pulse-labelling cultured cells with
      [3H]-thymidine. Incorporation of (3H)-thymidine was determined by liquid
      scintillation spectrophotometer. DNA content was measured by the fluorescence
      spectrophotometer. The lipid peroxidation was assayed with spectrophotometer.
      RESULTS: The results were as follows: 1) PG family (PGA1, PGD2, PGE1, PGE2,
      PGG2a, PGI2 & Thromboxane B2) stimulated the DNA synthesis of hepatocytes
      (especially PGD2 and PGE1), 2) ethanol decreased DNA synthesis by clear dose
      dependent manner, 3) the combined treatment of PGD2 or PGE1, prevents the
      decreasing of DNA synthesis, which was induced by ethanol, 4) in ethanol
      treatment, lipid peroxidation was decreased significantly, but PGD2, PGE1 and
      PGA1 were not affected, and 5) PGD2, PGE1 and PGA1 decreased lipid peroxidation
      with ethanol, significantly. CONCLUSIONS: From these results, we concluded that
      PG could be useful for the treatment of degenerative liver disease and alcohol
      induced liver disease in the assumption that further studies on the action
      mechanisms of PG will continue.

PMID- 9538625
TI  - Role of hyperinsulinemia and glucose intolerance in the pathogenesis of
      nonalcoholic fatty liver in patients with normal body weight.
AB  - OBJECTIVES: The pathogenesis of nonalcoholic fatty liver in non-obese persons is
      poorly understood. We aimed to elucidate whether hyperinsulinemia and glucose
      intolerance are associated with development of fatty liver in patients with
      normal body weight. METHODS: Forty-seven patients with fatty liver were divided
      into non-obese (n = 25) and obese groups (n = 22) according to age adjusted body
      mass index. Inclusion criteria were as follows: (1) elevated transaminase levels
      during more than 3 months of follow up period, (2) no detectable HBsAg or anti
      HCV in the serum, (3) alcohol consumption less than 40 gm/week, (4) no use of
      potential hepatotoxic drugs within 3 months and (4) sonographic evidence of fatty
      liver(moderate to severe degree). Baseline insulin levels and oral glucose
      tolerance test using 75gm of glucose were performed and the results were compared
      in each group of patients. RESULTS: Mean baseline insulin levels were elevated in
      both groups above the reference value, 9.3 +/- 3.5 microU/L in non-obese group
      and 9.9 +/- 3.5 microU/L in obese group (p = 0.26). Seventeen of non-obese
      patients (68%) had elevated basal insulin level and 16 of obese patients (73%)
      had elevated basal insulin level (p = 0.39). In oral glucose tolerance test,
      there was no difference in glucose level between non-obese and obese groups from
      O minute to 180 minutes (p > 0.05). Eleven patients from the non-obese group
      (44%) and 8 patients from the obese group (36%) had either impaired glucose
      tolerance or diabetes (p = 0.29). CONCLUSION: Our data suggest that
      hyperinsulinemia and glucose intolerance may play a role in the pathogenesis of
      fatty liver in patients with normal body weight as well as in patients with
      obesity.

PMID- 9538626
TI  - Effects of levosulpiride in patients with functional dyspepsia accompanied by
      delayed gastric emptying.
AB  - OBJECTIVES: Levosulpiride is the levo-enantiomer of sulpiride, a well-known
      antiemetic, antidyspeptic and antipsychotic drug. This study was undertaken to
      investigate the effects of levosulpiride on dyspeptic symptoms and gastric motor
      function in a group of patients with functional dyspepsia showing delayed gastric
      emptying. METHOD: Forty two eligible patients were entered into a 3 week, double
      blind randomized comparison of 25mg of levosulpiride or placebo t.i.d.. Symptom
      assessment and gastric scintigraphy following the intake of scrambled egg
      sandwich, were performed in each patient before and after treatment. RESULTS: The
      improvement of symptom score in levosulpiride group was higher than the placebo
      group (p < 0.05). We assessed global efficacy, which was excellent in 1 (6%),
      good 11 (65%), fair 4 (24%), nil 1 (6%) of those receiving levosulpiride, and
      fair 9 (60%), nil 5 (33%), poor 1 (6%) of those receiving placebo. Levosulpiride
      tended to be more effective than placebo in relieving the dyspeptic symptoms
      especially in the subgroups of dysmotility-like (p < 0.05) and nonspecific (p <
      0.05) as compared to other subgroups (p = 0.16). The reduction of gastric
      emptying time after levosulpiride treatment was more marked than Placebo group (p
      < 0.05). We found a significant correlation between changes of symptom score and
      gastric emptying time (r = 0.47, p = 0.01). No serious adverse effects were
      reported after administration of either levosulpiride or placebo. Only two
      patients reported mild somnolence during levosulpiride administration.
      CONCLUSIONS: Levosulpiride is effective and well tolerated in patients with
      functional dyspepsia accompanied by delayed gastric emptying. Its efficacy may be
      related to its action on the gastric motor function by improving the delayed
      gastric emptying.

PMID- 9538627
TI  - Changes of the carotid artery Doppler flow velocity pattern after sublingual
      nitroglycerin in patients with hypertension.
AB  - OBJECTIVE: To evaluate the applicability of carotid Doppler echography for the
      assessment of changes of peripheral hemodynamics in the hypertensives. SUBJECTS:
      28 hypertensives (17 males, 11 females), mean age of 64 yrs and 40 normal
      controls (24 males, 16 females) mean age of 49 yrs. METHODS: We recorded the
      right common carotid arterial Doppler flow velocity (BFV) pattern and measured
      the peak velocities of the percussion wave (P) and late rising tidal wave (T),
      the ratio of the two (P/T), the time interval between the two peaks corrected by
      heart rate (P-Tc), systolic flow velocity integral (FVI) and carotid artery
      diameter (CAD) before and after 0.4 mg dose of subligual nitroglycerin (NTG).
      RESULTS: 1) In hypertensives, the P wave velocity showed lower and P-Tc interval
      shorter than those of the normal controls at baseline. 2) After NTG, the P-Tc and
      P/T increased, but the T and FVI decreased significantly in both groups of
      subjects. 3) The P/T ratio was less significantly increased after NTG in the
      hypertensives than in the controls. These results suggest that NTG might have
      been involved in concomitant reduction and delay of the wave reflection from the
      peripheral vessels, preferentially in the normal subjects than in hypertensives.
      CONCLUSIONS: The carotid Doppler echography can be useful for the evaluation of
      the changes of hemodynamics in the peripheral vessel such as carotid artery in
      hypertensive subjects.

PMID- 9538628
TI  - Role of mononuclear cells of IgA nephropathy on ICAM-1 expression in mesangial
      cells.
AB  - OBJECTIVES: To investigate the possible role of mononuclear cells and their
      products in the pathogenesis of IgA nephropathy, in vitro expression of ICAM-1 on
      cultured mouse mesangial cell (MC) was examined after stimulation with
      mononuclear cell culture supernatant from patients with IgA nephropathy. METHODS:
      Peripheral blood mononuclear cells (PBMC) were isolated and cultured from 18
      patients with primary IgA nephropathy, 8 normal controls and 5 patients with non
      IgA nephropathy (FSGS 1, MGN 3, MPGN 1). ICAM-1 expression on cultured mouse MC
      by TNF-alpha, IL-1 beta and culture supernants of PBMC were analyzed using a cell
      ELISA method. The concentration of IL-1 beta and TNF-alpha in culture
      supernatants was measured by using a commercially available radioimmunoassay kit.
      RESULTS: Addition of human recombinant TNF-alpha induced an increased ICAM-1
      expression in a dose-dependent manner. The expression of ICAM-1 was further
      increased after co-stimulation with TNF-alpha and IL-1 beta. Addition of PBMC
      culture supernatants into mouse MC induced significantly higher expression of
      ICAM-1 by supernatants from the patients with IgA nephropathy compared with that
      from normal controls. The concentration of TNF-alpha and IL-1 beta in
      supernatants from the patients with IgA nephropathy was significantly higher than
      that from those with non-IgA nephropathy. CONCLUSION: TNF-alpha and IL-1 released
      from mononuclear cells induced the up-regulation of ICAM-1 expression and this
      may be related to the immune pathogenesis of IgA nephropathy.

PMID- 9538629
TI  - Comparison of plasma amino acid concentrations in end-stage renal disease
      patients on hemodialysis and peritoneal dialysis.
AB  - OBJECTIVES: Recent reports have suggested that patients treated by CAPD have a
      relatively increased risk of death compared to patients undergoing HD, although
      the cause of this discrepancy is poorly understood. Protein malnutrition is an
      important risk factor in ESRD. Also, amino acid concentrations, for which the
      physiological function differs from that of protein, may be an independent risk
      factor in ESRD. There is no doubt concerning the prevalence of low amino acid
      levels in both HD and CAPD patients. But the difference in plasma amino acid
      levels between these two groups has not been well defined. The purpose of this
      study is to compare plasma amino acid levels between patients with ESRD on HD and
      CAPD. METHODS: A cross sectional study of overnight fasting plasma amino acid
      concentrations was performed on 12 CAPD and 45 HD patients with ESRD, matched by
      age, sex and body mass index. The levels of individual plasma amino acid and TAA,
      EAA, NEAA and BCAA were compared for the HD and CAPD groups. In order to measure
      losses during HD and CAPD, amino acid and protein concentrations were measured
      from 10 dialysates obtained from 10 HD patients and 12 peritoneal dialysis
      solutions from 12 CAPD patients. RESULTS: All of the measured amino acid
      concentrations were found to be lower in the CAPD group compared to the HD group.
      Furthermore, the levels of TAA (2017.3 +/- 781.1 vs. 903.3 +/- 316.1 mumole/L),
      EAA(1201.8 +/- 492.6 vs. 567.6 +/- 223.2 mumole/L), NEAA(815.5 +/- 308.6 vs.
      335.7 +/- 100.2 mumole/L); and BCAA (315.0 +/- 146.0 vs. 145.2 +/- 65.0
      mumole/L), were all lower in the CAPD group than in the HD group. The protein
      loss was 2.0 +/- 0.2 g/L in the peritoneal dialysate but was not detectable in
      the hemodialysates. TAA loss over a one week period was about 61.8 +/- 13.0mmole
      for the HD group and 38.0 +/- 13.0 mmole for the CAPD group. CONCLUSIONS: Our
      results show that amino acid concentrations are lower in ESRD patients on CAPD
      than on HD. It seems likely that protein loss in the peritoneal dialysate is a
      contributing factor to lowered plasma amino acid concentrations in ESRD patients
      on CAPD than on HD. We believe that the lowered amino acid concentrations
      observed in CAPD patients may worsen the clinical outcome compared to HD
      patients.

PMID- 9538630
TI  - Delayed activation-induced T lymphocytes death in aplastic anemia: related with
      abnormal Fas system.
AB  - OBJECTIVES: To quantitate apoptosis and Fas antigen expression of T lymphocytes
      by activation in aplastic anemia (AA) and compare with that of normal controls
      and completely-recovered AA, and to investigate the apoptotic sensitivity to anti
      fas antibody of activated T lymphocytes in AA. METHODS: We studied the expression
      of Fas antigen on fresh T lymphocytes of twenty patients with AA [13 newly
      diagnosed, 7 recorvered AA after immunosuppressive therapy (IST)], and
      investigated the activation-induced cell death (AICD) and Fas expression by
      activation [interleukin-2 (200 U/ml) and phytohemagglutinin (50 micrograms/ml)]
      in 5 newly-diagnosed AA, 5 normal controls and 5 AA in complete response (CR).
      Apoptotic sensitivity to anti-Fas antibody was assessed by the time-course
      kinetics of induction of cell death by anti-Fas antibody (500 ng/ml). RESULTS:
      There was no significant difference of Fas antigen expression on freshly-isolated
      T lymphocytes among newly-diagnosed severe AA, normal controls and patients with
      AA in CR after IST. In normal controls, T lymphocytes death was greatly increased
      at 3 days of activation, and Fas antigen expression on T lymphocytes was
      increased above baseline at day 1 of activation. In contrast, in newly-diagnosed
      AA, T lymphocytes showed delayed cell death, which correlated with a slowed
      increase of Fas antigen expression by activation. Also, anti-Fas antibody
      sensitivity of activated T lymphocytes was decreased in newly-diagnosed AA. In
      completely recovered AA, these abnormal AICD and Fas antigen expressions by
      activation were recovered to normal range. CONCLUSIONS: Abnormal AICD plays a
      role in the immune pathophysiology of AA, and defective Fas system is involved in
      this process.

PMID- 9538631
TI  - Ultrastructure of neuromuscular junction in vacor-induced diabetic rats.
AB  - OBJECTIVES: Rodenticide Vacor causes a severe peripheral neuropathy in humans.
      Electrophysiologic studies on a peripheral motor nerve-skeletal system of Vacor
      treated rat showed decreased amplitude of muscle action potential without
      conduction velocity abnormalities. The ultrastructural studies of the
      neuromuscular junction were performed to clarify the anatomic site of the Vacor
      induced peripheral neuropathy in male Wistar rats. METHODS: After oral
      administration of a single dose of Vacor, 80 mg/kg of body weight, to the
      experimental animals, neuromuscular junctions within the interosseous muscles of
      the hind foot were observed in time. RESULTS: No axon terminal change was noted
      until 24 hours after the administration of Vacor. Remarkable loss of presynaptic
      vesicles and swollen endoplasmic reticulum in the axon terminal were developed at
      3 days after Vacor treatment. Progressive degenerative changes consisting of
      marked loss of presynaptic vesicles, focal disruption of membrane in the axon
      terminal with disappearance of the number of the damaged axon terminal appeared,
      and flattening of postsynaptic folds was also seen. CONCLUSIONS: These results
      suggest that degenerative changes in axon terminal at neuromuscular junction may
      contribute to the peripheral neuropathy developed in the early phase of Vacor
      poisoning.

PMID- 9538632
TI  - Role of circulating immune complex in aspirin-sensitive asthma.
AB  - BACKGROUND & OBJECTIVES: The pathogenic mechanism of aspirin-sensitive asthma
      (ASA-BA) remains to be further defined. To evaluate the role of circulating
      immune complex (CIC) in ASA-BA. SUBJECTS & METHODS: We measured IgG- and IgA-IC
      level by ELISA using anti-C3 antibody in 33 ASA-BA patients whose sensitivity was
      confirmed by lysine-aspirin bronchoprovocation test, and compared with those of
      14 allergic, 14 intrinsic asthma patients and 7 healthy controls. RESULTS: There
      was no significant difference in IgG-IC level among the four groups (p > 0.05),
      while IgA-IC levels of aspirin-sensitive asthma were higher than those of other
      groups (p = 0.0035). Patients with nasal polyp had significantly higher IgG-IC
      than those without it (p = 0.02). No differences were found according to
      medication and symptom scores, and presence of atopy, rhino-sinusitis, urticaria
      or concurrent sensitivity to sulfite (p > 0.05). Insignificant correlation was
      found between IgG-IC level and asthma duration, total IgE level, or circulating
      eosinophil count. CONCLUSION: These findings suggest a possible contribution of
      IgG-IC to the development of nasal polyp in ASA-BA. Further study will be needed
      to clarify the role of IgA-IC in the pathogenesis of ASA-BA.

PMID- 9538633
TI  - Massive bleeding from left colonic arteriovenous malformation in a young patient
      with ventricular septal defect.
AB  - Arteriovenous malformation of the gut is well known to have been an important
      bleeding focus in past ages. We report a young Korean male patient, who had been
      known to have ventricular septal defect, presenting massive lower
      gastrointestinal bleeding from an arteriovenous malformation involving a long
      segment of the left colon. Angiographic, gross and histologic findings are
      presented and the literature is reviewed.

PMID- 9538634
TI  - A case of chronic graft-versus-host-disease following allogeneic peripheral blood
      stem cell rescue for poor graft function after bone marrow transplantation.
AB  - To overcome poor graft function after allogeneic bone marrow transplantation
      (BMT), the use of peripheral blood stem cells (PBSC) instead of bone marrow is
      gaining more popularity because of its advantages. There may, however, be an
      increased risk of graft-versus-host-disease (GVHD) because of the large number of
      lymphocytes present in a leukapheresis product. An 18-year-old man with severe
      aplastic anemia underwent an allogeneic BMT using his HLA-identical sister. After
      initial excellent graft take for 8 months, his blood counts gradually decreased
      to 2.8 x 10(9)/L of white cells and 28 x 10(9)/L of platelets with marrow
      cellularity of < 10%. After allogeneic granulocyte-colony stimulating factor
      mobilized PBSC rescue, the patient's blood counts recovered satisfactorily.
      Around 1 year after the boost, he developed chronic GVHD that responded to
      prednisolone and cyclosporin A. He is now well on low-dose steroids at day +1055
      after PBSC rescue. The present case is the first experience of a long-term follow
      up who underwent allogeneic PBSC rescue in Korea.

PMID- 9538636
TI  - A case of Wegener's granulomatosis complicated by diffuse pulmonary hemorrhage
      and thrombotic thrombocytopenic purpura.
AB  - Wegener's granulomatosis is a distinct form of necrotizing granulomatous
      vasculitis which usually affects the kidneys and the upper and lower respiratory
      tracts. Unusual manifestations have also been reported, and these include
      colitis, urethritis and diabetes insipidus. We describe a case of Wegener's
      granulomatosis which presented with rapidly progressive renal insufficiency,
      sudden deafness, red eye, facial palsy, and complicated by uncommon
      manifestations that were diffuse pulmonary hemorrhage and thrombotic
      thrombocytopenic purpura.

PMID- 9538635
TI  - Pancytopenic prodrome (pre-ALL) of acute lymphoblastic leukemia in adults:
      possible pathogenesis.
AB  - We report two cases of adult acute lymphoblastic leukemia presenting with
      preleukemic phase of pancytopenia with a few abnormal lymphoid cells in bone
      marrow aspirates. The initial diagnosis of each case was suspicious aplastic
      anemia and hypoplastic anemia. Both cases progressed to overt acute lymphoblastic
      leukemia within 1 year. We suggest that initial pancytopenic phase (pre-ALL) may
      precede the diagnosis of acute lymphoblastic leukemia in adults and differential
      diagnosis from myelodysplastic syndrome and primary aplastic anemia will be
      needed. We also suggest that primary bone marrow lymphoma and "primary unknown
      metastatic lymphoma of bone marrow" may be possible as the pathogenesis in a case
      like ours.

PMID- 9538637
TI  - A case of Behcet's syndrome with supeior vena cava syndrome.
AB  - Behcet's syndrome is a multi-systemic and chronic disorder that affects many
      organs. It has been suggested that the diagnosis was based on the presence of the
      'major' and 'minor' clinical criteria. When thromobophlebitis, arthritis, central
      nervous system or gastrointestinal lesions are also present. Behcet's syndrome
      will be thought to be present in the appropriate geographic area. We report a
      case of superior vena cava syndrome caused by Behcet's disease in a 40-year-old
      man with recurrent oral aphthous ulcers and skin rashes on the anterior chest
      wall. There were multiple thrombosis of the superior vena cava, innominate and
      subclavian veins. This patient also had a solitary cecal ulcer with an ileocecal
      fistula and downhill varix. The chest CT, veno-cavography, pulmonary angiography
      and colon study were taken and follow-up was performed.

PMID- 9538638
TI  - [Results of radiotherapy in the year of the Rontgen centenary].
AB  - In 1996, the three leading radiation oncology periodicals (Int. J. Radiat. Oncol.
      Biol. Phys.--USA, Radiother. Oncol.--Europe, and Strahlenther. Onkol.--Germany)
      published 681 papers. Among the different topics, the clinical subjects accounted
      for almost half (46%) of the total number of publications, followed by radiation
      physics/techniques (18%) and radiation biology (17%). The 13% of
      editorials/review articles reflects a considerable endeavor towards integration;
      the contribution of papers relating to professional organization amounted to 2%.
      The fact that 1996 was the centennial year of the discovery of the Rontgen rays
      explains the reasonable proportion (4%) of historical reviews. Within the special
      topics, prostatic cancer and breast cancer were the two most frequent issues.
      Dose escalation was the most important tool applied to improve the results of the
      radiation therapy of tumors with unfavorable prognostic signs or radioresistance.
      The increase in the applied dose was made possible by a decrease in the planning
      target volume (PTV), 3D forward and inverse radiation treatment planning, a
      combination of tomographic (CT/MRI/US) diagnostic methods (image
      registration/fusion), optimizing algorithms, computer-controlled delivery of
      radiation dose and electronic portal imaging with in vivo dosimetry. In contrast,
      the trends in the radiotherapy of tumors with favorable long-term survival (e.g.
      Hodgkin's disease and seminoma) include a decreased dose and PTV reduction to
      diminish the late, radiation-related morbidity. Fractionation has remained the
      only tool of radiobiology routinely used in the everyday clinical practice. A
      comparison of the results and achievements in the special fields reveals that
      radiation physics/techniques clearly outstrip clinical subjects and especially
      radiation biology, as they allow direct and instant exploitation of the
      advantages offered by computers. It is highly probable, however, that, subsequent
      to a wider use of computers in clinical subjects and radiation biology, this
      situation will change.

PMID- 9538639
TI  - [Notching of the bilateral uterine artery flow velocity wave-forms in the third
      trimester and perinatal complications].
AB  - Pulsatile color duplex Doppler ultrasonography system was used to study blood
      flow velocity waveforms in the uterine arteries of 492 pregnant women in the
      third trimester. In 38 (7.7%) patients unilateral and in 42 (8.5%) bilateral
      postsystolic notches were observed. Those with bilateral early diastolic notches
      experienced poor perinatal outcome in 40 (95.2%) instances. The same occurred in
      16 (42.1%) others with unilateral notches and in 13 (3.2%) without notches but
      with evidence of increased impedance (pulsatility index > 1.20, resistance index
      > 0.58 and systolic/diastolic ratio > 2.6). The presence of bilateral
      postsystolic notches in the uterine artery flow velocity waveforms appears to be
      a reliable predictor of poor pregnancy outcome.

PMID- 9538640
TI  - [Nephrogenic diabetes insipidus].
AB  - The syndrome of polyuria and polydipsia is practically identical in three very
      different disorders (central diabetes insipidus, nephrogenic diabetes insipidus,
      primary polydipsia). In congenital nephrogenic diabetes insipidus both the thirst
      mechanism and the production of the antidiuretic hormone are intact, but the
      hormone is ineffective in the kidney. The acquired form of the disease is caused
      most frequently by tubulointerstitial and urinary tract obstructive disorders as
      well as among the several drugs, lithium. In the differential-diagnosis the
      results of determinations related to the nomograms of normal interrelationships
      between osmolality and vasopressin in urine and plasma are used, besides the
      classical Carter-Robbins and indirect dehydration (Miller) tests. It has been
      postulated recently that in many cases the resistancy toward vasopressin is not
      absolute and these partially vasopressin sensitive patients can be treated
      successfully by thiazide, and potassium sparing compounds, antiprostaglandin pain
      killers (non-steroid antiinflammatory drugs) and first of all dDAVP as well as
      combinations of these preparations.

PMID- 9538641
TI  - [Pseudoaneurysm of the thoracic aorta diagnosed by transesophageal
      echocardiography].
AB  - Transesophageal echocardiography is a sensitive and specific procedure that gives
      one of the best opportunities to examine thoracic aortic anatomy and blood flow.
      The non-traumatic disruption of the aorta is a life threatening injury that
      requires rapid diagnosis and treatment. Two cases are presented which were shown
      to have pseudoaneurysm of the thoracic aorta by noninvasive methods. The
      etiologic factor was atherosclerotic vascular disease in both cases. We performed
      transesophageal echocardiography first and confirmed the diagnosis by gated
      magnetic resonance imaging and by autopsy. These cases highlight the value of
      techniques such as these to reliably asses the heart and great vessels without
      the need of more invasive procedures.

PMID- 9538642
TI  - [Observation in two cases of Whipple disease].
AB  - The authors survey the literature of Whipple's disease and present two of their
      patients. They assure that Whipple's disease in either associated with or is a
      result of an immunopathological clinical picture, but it is else possible that
      assumed pathogen, the Tropheryma whippleii itself alters the immune system. In
      the case of their female patient with active disease they showed the
      rearrangement of the bcl-2 gene [t(14; 18)] in her peripheral blood lymphocytes,
      while in their male patient in remission this could not be proved. During the
      observation, in their female patient insulin dependent diabetes mellitus (IDDM)
      developed. In connection with these cases, the authors draw the attention to the
      varied symptoms which are characteristic of autoimmune disease, and to the
      immunoserological laboratory differences in particular the rearrangement of the
      bcl-2 gene.

PMID- 9538643
TI  - [Bela Korpassy, professor of pathology].

PMID- 9538644
TI  - [Kalman Mikszath, his health, his diseases and his "white table"].

PMID- 9538645
TI  - [Medical-historical monuments in the city of Villach (Paracelsus)]].

PMID- 9538646
TI  - [The role of echocardiographic tests with dipyridamole for diagnosis and
      evaluation of ischemic heart disease].

PMID- 9538647
TI  - [Plasma serine protease inhibitors in dialyzed patients with chronic renal
      insufficiency].
AB  - In the plasma of fourty dialyzed patients with chronic renal insufficiency in
      comparison to controls a mild decrease of AT III activity, low activity of PAI-1
      and alfa-2 AP with normal activity alfa-2 M. and alfa-1 PI were observed.
      Hemodialysis with the presence of heparin except of mild shortness of ELT did not
      influenced the activities of the inhibitors in the plasma of the patients. The
      decrease of PAI-1 and alfa-2 AP activity with increased FDP concentration in the
      dialyzed patients can suggests the occurrence of secondary fibrinolysis
      activation with consumption of these inhibitors.

PMID- 9538648
TI  - [Results of two year use of dipyridamole and metindol in patients with primary
      focal and (or) segmental glomerulosclerosis].
AB  - Primary focal or segmental glomerulosclerosis is neuropathy diagnosed in 10% of
      children and 20% of adult patients with nephrotic syndrome. Immunosuppressive
      therapy was applied during two years period. The very good clinical results were
      obtained in 20% and good results in 40% of patients after indomethacin and
      dipyridamole therapy.

PMID- 9538649
TI  - [Use of "rinoflow" inhalation in treatment of paranasal sinusitis].
AB  - The inflammatory pathologies of the ENT tract are often characterized by presence
      of catarral, mucous-purulent and crusty secretions. In such cases, an efficient
      therapy has to change the dense secretions as first and then remove them.
      "Rinoflow" is a compressor-micronizer chamber system specially designed for
      treatment of affections of upper respiratory tract. We used Rinflow in treatment
      of 62 patients (23 female and 39 male, mean age 42.7 years) with chronic
      paranasal sinusitis. The results of treatment were estimated by patients,
      physicians and X-ray examinations. We observed in 37 patients (59.7%) good
      results after treatment. The use of "rinoflow" was practically effected when the
      secretions were blocking the natural ostium of paranasal sinuses.

PMID- 9538650
TI  - [Clinical significance of atrial signal-averaged electrocardiogram in patients
      with electrically-induced paroxysmal atrial fibrillation].
AB  - The aim of this study was to assess the diagnostic possibilities of recording of
      time-domain parameters of atrial signal-averaged electrocardiogram (ASAECG) in
      patients with electrically-induced paroxysmal atrial fibrillation (PAF). The
      investigation was done in 53 patients (34 male and 19 female) mean age 47.6 +/-
      13.1 with electrically induced sustained PAF- > 30 sec (group I). As a controls
      were forty patients (28 male and 12 female) mean age 46.2 +/- 15.3 (group II).
      The following time-domain parameters of ASAECG were calculated: the root mean
      square voltage of the terminal 10,20,30 ms of the filtered P-wave (RMS10,20,30)
      and total duration of filtered P-wave (PWD) and also time duration of P-wave from
      Frank's leads X,Y,Z (XP,YP,ZP). The values of RMS10,20,30 were statistically
      significant lower in patients with PAF than in controls, respectively RMS10: 3.9
      +/- 1.4 microV vs 5.4 +/- 2.3 microV, p < 0.005, RMS20: 5.3 +/- 2 microV vs 6.8
      +/- 2.2 microV, p < 0.001 and RMS30: 6.8 +/- 2.1 microV vs 7.4 +/- 3.6 microV, p
      < 0.05. Also the values of PWD were significantly longer in group I: 121 +/- 14.6
      ms than in group II: 113.9 +/- 13.5 ms, 1 p < 0.02. Analysing the values of
      XP,YP,ZP it's occurred that only YP in PAF patients was statistically longer than
      in control, respectively 111 +/- 14.8 ms vs 96.7 +/- 13.8 ms, p < 0.001. The best
      differential criteria for identification of patients with electrically-induced
      PAF were RMS20 < 6 microV and PWD > 118 ms and gave sensitivity of 52%,
      specificity of 79%, positive predictive value of 68%, negative of 66% and
      diagnostic accuracy of 67%. CONCLUSIONS: 1. In patients with electrically-induced
      PAF the lower values of RMS10,20,30 and longer PWD were detected. 2. The criteria
      for identification of patients with electrically-induced paroxysmal atrial
      fibrillation were the values of RMS20 < 6 microV and PWD > 118 ms.

PMID- 9538651
TI  - [Twenty-four hour heart rate variability in patients with acute myocardial
      infarction depending on treatment].
AB  - Heart rate variability is a useful prognostic parameter in patients with coronary
      artery disease. SDNN (standard deviation of all normal RR intervals in the entire
      ECG 24 hour recording) was evaluated in patients with acute myocardial infarction
      (AMI), who were divided in two groups: The first group consisted of 22 patients
      who had not received streptokinase; in the second group there were 10 patients,
      who were treated with streptokinase and in whom indirect reperfusion criteria
      were observed. Two control groups were drawn into the study: the third included
      30 patients with stable ischaemic heart disease with no history of myocardial
      infarction and the fourth group of 18 healthy subjects. SDNN was calculated by
      the ECG Mediarc Premier II Holter System (DRG International Inc., NJ, USA) in the
      time domain from 24 hour ECG recordings. Mean SDNN divided by standard deviation
      values were: I: 88.1 divided by 25.1 ms; II: 96.7 divided by 24.3 ms; III: 107.5
      divided by 22.6 ms; IV: 136.0 divided by 20.4 ms. No significant difference in
      SDNN was found between heart infarct patients, who were and were not thrombolyzed
      (96.7 divided by 24.3 ms vs. 88.1 divided by 25.6 ms; p > 0.05) as well as
      between thrombolyzed infarct patients and patients with stable ischaemic heart
      disease with no history of myocardial infarction (96.7 divided by 24.3 ms vs.
      107.5 divided by 22.6 ms; p > 0.05). However, a significant difference in SDNN
      was observed between patients who had not been thrombolyzed and patients with
      stable ischaemic heart disease (88.1 divided by 25.6 ms vs. 107.5 divided by 22.6
      ms; p < 0.01).

PMID- 9538652
TI  - [The influence of verapamil on platelet function in patients with multiple
      myeloma].
AB  - Influence of verapamil on platelet function was evaluated in 7 female and 8 male
      patients with myeloma. The inhibitory effect on platelet aggregation and other
      parameters was documented in clinical observation.

PMID- 9538653
TI  - ["Back pain" in teenagers and young adults].
AB  - The studies aimed to estimate an incidence of the low back pain (LBP) in the
      youngsters and teenagers and correlating it with risk factors. A groups of 2,346
      secondary school pupils (1,704 girls and 642 boys) of a mean age 17 +/- 1 yrs,
      and 970 high-school students (532 women and 438 men) of a mean age 24 +/- 2 yrs
      have been examined. Low back pain has been seen in 1,416 out of 2,346 secondary
      school pupils (60%), and in 32% of the examined students. Statistical analysis
      with chi 2 test has confirmed a correlation between LBP and such risk factors as
      the incorrect sedentary position (p < .001 for pupils, and p < .02 for students),
      and smoking (p < .001 for students and p < .02 for pupils).

PMID- 9538654
TI  - [Treatment results for rhabdomyosarcoma in children].
AB  - The results of treatment in 45 children with rhabdomyosarcoma was presented. Two
      years survival was achieved in 63% and five-year in 45%. The importance of
      location and group of clinical progression discussed was importance prognostic
      factors in rhabdomyosarcoma.

PMID- 9538655
TI  - [Possibility of using saliva for therapeutic monitoring of digoxin].
AB  - Digoxin in salvia and blood serum of 24 patients obtained Bemecor was determined
      by the method of FPIA (IMx-ABBOT). Mixed saliva was collected by three different
      types of Salivette (Sarstedt) given in order: normal Salivette with cotton wool
      swab, Slivette with polyester wool and Salivette with citric acid as a
      stimulator. It was found, that the correletio between the digoxin concentrations
      in saliva and serum and saliva/serum rations depended on the type of Salivette.
      The highest correlation was obtained with the Salivette with polyester wool (r =
      0.892), but low concentrations of this drug in serum were good reflected in all
      samples of saliva, independent on kind of Salivette.

PMID- 9538656
TI  - [Problems with diagnosis and treatment of an odontogenic fistula of facial skin].
AB  - Out of 16 patients with odontogenic fistulae of the facial skin, treated with in
      the last two years in the Department of Maxillofacial Surgery, Province Hospital
      No 1 in Rzeszow, the authors subjected to detailed analysis seven patients in
      whom, during the period preceding specialist stomatological treatment,
      difficulties occurred in the diagnosis and treatment. In all cases of development
      of facial skin fistulae, odontogenic origin should be considered in the first
      place.

PMID- 9538657
TI  - [Evaluation of antiarrhythmic efficacy of sotalol in various doses in patients
      with ventricular tachyarrhythmias].
AB  - Antiarrhythmic efficacy of sotalol--noncardioselective beta-adrenergic blocking
      agent with class III antiarrhythmic action was evaluated in 34 patients [pts]
      (mean age 55 +/- 11) with chronic ventricular arrhythmias and coronary artery
      disease, 38% with previous myocardial infarction. Two schedules of dosing were
      tested: 3 x 80 mg and 2 x 160 mg during 28 days of therapy. Pts with Lown class
      II and IV arrhythmia derived from 24-hours Holter recording were assigned.
      Ventricular premature complexes [VPCs] and couplets reduction by 80% and total
      elimination of runs defined antiarrhythmic efficacy. Proarrhythmia was defined by
      four times increase in VPCs, ten times increase in couplets and runs or sustained
      VT episodes. RESULTS: Antiarrhythmic efficacy of two doses of sotalol according
      to study criterion was: 31% for lower dose (3 x 80 mg) and 24% for higher dose (2
      x 160 mg). Overall efficacy for both doses was 55%. According to Morganroth
      criterion, lower dose was effective in 29% pts and both doses, lower and higher,
      in 41% pts. According to other commonly used criterion: 70% VPCs reduction, 90%
      couplets reduction and total elimination of runs, lower dose of sotalol was
      effective in 32% pts and both doses in 47% pts. Significant reduction of heart
      rate and prolongation of QT and QTc were observed. In 3 pts QT was prolonged over
      500 ms. Proarrhythmia according to Velebit criterion was suspected in one patient
      after one week of 3 x 80 mg teratment which caused premature cessation of
      therapy. No significant abnormalities in laboratory values were observed.
      CONCLUSIONS: Antiarrhythmic efficacy of sotalol was comparable to other studies.
      Its value in pts with malignant ventricular tachyarrhythmias: sustained
      ventricular tachycardia and ventricular fibrillation requires further studies
      with higher number of patients.

PMID- 9538658
TI  - [Inhaled glucocorticosteroids in treatment of bronchial asthma].
AB  - Studies of bronchial asthma pathogenesis, conducted over many years, have shown
      that inflammatory process plays a major role in the development of this disease.
      Glucocorticosteroids are agents with strongest antiinflammatory activity and
      together with beta 2-agonists are thought of as firstline therapy in the
      treatment of bronchial asthma. New inhaled glucocorticosteroids are preparations
      with small systemic activity, despite the fact, that some of them are more
      lipophyllic than the others, despite the differences in solubility, affinity to
      lung tissue, different serum concentrations and affinity to receptors. Even with
      the tremendous progress in increasing efficacy and lowering side effects of
      inhaled glucocorticosteroids, no ideal preparation was found so far, however the
      antiinflammatory activity was increased and the dose lowered, which means
      increasing clinical efficacy and lowering the systemic effects. Only in the
      future we can hope for developing an ideal preparation of inhaled
      glucocorticosteroid with common specificity towards lung tissue and direct
      influence on the target cell, and maybe even on a specific gene.

PMID- 9538659
TI  - [Familial hypertrophic cardiomyopathy].
AB  - Investigating the family consisted of 8 members authors confirmed the diagnosis
      of hypertrophic cardiomyopathy in 5 cases. Secondly clinical features and
      echocardiographic data were compared. The clinical symptoms were not proportional
      to the pattern of hypertrophy revealed by echocardiography. The most significant
      pattern of hypertrophy was registered in youngest patients most likely due to
      increased expression and penetration of responsible genes. Considering
      cardiomyopathy as an inherited disease authors find family screening as a key in
      understanding and management of the disease.

PMID- 9538660
TI  - [Two cases of Lambert-Eaton syndrome with an increase of serum cholinesterase
      activity].
AB  - Paraneoplastic Lambert-Eaton myasthenia syndrome is presented in two cases with
      small cell lung cancer. An increase of serum cholinesterase activity was
      explained by induced release of biologically active proteins by neoplastic
      tissue.

PMID- 9538661
TI  - [Autologous peripheral blood stem cell transplantation as an effective treatment
      for recurrent Hodgkin's disease].
AB  - Autologous peripheral blood stem cell transplantation (APBSCT) is a method used
      analogically to autologous bone marrow transplantation (ABMT) to obtain
      hematological reconstitution following myeloablative therapy in patients with
      hematological malignancies. We have now applied this procedure in two patients
      with recurrent high risk Hodgkin's disease. Collection of circulating stem cells
      mobilised with cyclophosphamide/G-CSF was performed by several leukaphereses on
      Fenwal 3000, with access through inferior vena cava. Nucleated cells were
      separated by dextran sedimentation, cryopreserved, and stored at (-) 196 degrees
      C. Additional marrow collection was performed in one patient. Conditioning
      regimen consisted of BCNU, etoposide and cyclophosphamide delivered at days -3
      and -2. Collected material containing on average 3.6 x 10(8)/kg nucleated cells
      and 8.0 x 10(6)/kg CD34(+) cells was transfused at day 0. G-CSF was administered
      following transplantation to one patient to hasten the recovery. Hematological
      recovery was relatively quick. Neither serious adverse events nor signs of
      relapse were observed following transplantation. Our results supported by other's
      reports indicate, that APBSCT enables hematological recovery similarly to ABMT in
      Hodgkin's disease. The advantage of APBSCT is a possibility to collect material
      in patients with marrow involvement, hypoplasia or fibrosis. Outcomes obtained
      following APBSCT are at least as good as following ABMT. High-dose chemotherapy
      followed by APBSCT or ABMT should be considered in all patients with recurrent
      Hodgkin's disease sensitive to chemotherapy.

PMID- 9538662
TI  - [Effect of antihypertensive therapy on levels of lipids, lipoproteins and glucose
      in serum of patients with primary hypertension].

PMID- 9538663
TI  - [Theories of intracranial aneurysm etiology].
AB  - The main theories of the origin of intracranial aneurysms as the most common
      vascular malformations are presented. Three main theories maintain that they are
      either the congenital, acquire or both of those defects. The presence of
      aneurysms in the bifurcations of the arteries with the loss of the muscle layer
      and the coexistence with other vascular malformations of the arteries and their
      rareness in children give the evidence of the acquire origin. The present
      theories join this two positions and take into consideration also the hemodynamic
      and inflammation as well as degeneration, atheromatosis, toxic and traumatic
      factors.

PMID- 9538664
TI  - [Views on the etiopathology of chronic subdural hematoma and methods of
      treatment].

PMID- 9538665
TI  - [Intra-uterine fetal death syndrome--not only a gynecologic problem].
AB  - Intra-uterine fetal death may seriously affect maternal health and implies
      considerable risk of maternal death, especially when clotting and septic
      disorders arise. Management od IUFD should include removal of the triggering
      mechanism for DIC, antiinfectious prophylaxis and consider prompt evacuation of
      uterus. Low-dose heparin therapy is safe and offers sufficient protection against
      coagulopathy associated with IUFD. Treatment with low-dose aspirin, steroids or
      substitutive ACTH therapy is useful for patients with a poor obstetrical outcome.
      Etiopathology of IUFD, complications, methods terminating of the pregnancies has
      also been presented.

PMID- 9538667
TI  - [Evaluation of the cytotoxic food test and the ALCAT (antigen leukocyte cellular
      antibody test)].

PMID- 9538666
TI  - [About the Heimlich maneuver once again].

PMID- 9538668
TI  - Childhood memories of sexual and physical abuse. Dr. Milton Rosenbaum's
      perspective.

PMID- 9538669
TI  - Use of herbal medicines among consultation-liaison populations. A review of
      current information regarding risks, interactions, and efficacy.
AB  - Consultation-liaison psychiatrists evaluate a wide variety of patients who are
      often disillusioned with conventional medical care and are seeking to gain some
      measure of control over their illness. With the growing popularity of alternative
      health care practices, consultation-liaison psychiatrists must learn more about
      the implications of herbal medicine usage. This review provides an overview of
      herbal medicines, a vital component of the alternative medicine movement.

PMID- 9538670
TI  - An open clinical trial of venlafaxine treatment of fibromyalgia.
AB  - Of 15 patients with fibromyalgia who were first evaluated for the presence of
      Axis I psychiatric diagnoses by use of the Structured Clinical Interview for DSM
      IV, 11 completed an open 8-week trial with the novel antidepressant venlafaxine.
      Six (55%) of 11 completers experienced a > or = 50% reduction of fibromyalgia
      symptoms. The presence of lifetime psychiatric disorders, particularly depressive
      and anxiety disorders, predicted a positive response to venlafaxine. These
      findings suggest that it is important to assess for comorbid psychiatric
      disorders in patients with fibromyalgia and that venlafaxine may be helpful to
      some of these patients.

PMID- 9538671
TI  - Assisted suicide and AIDS patients. A survey of physicians' attitudes.
AB  - Physicians' attitudes about assisted suicide were assessed by using a vignette of
      an acquired immune deficiency syndrome (AIDS) patients who requests a lethal
      injection. Of the 389 respondents, 34% received at least 1 request for assisted
      suicide; 9% had requests from an AIDS patient; and 41% had at least indirectly
      assisted a terminal patient to die in actual practice. Thirty-three percent of
      the respondents agreed to the authors' hypothetical patient's request for a
      lethal injection. Medical and personal experiences did not determine attitudes
      that were somewhat influenced by ethical beliefs and religious commitment. The
      study confirms previous findings that many physicians underestimate the effect of
      depressive illness on rational decision making concerning assisted suicide the
      effect of depressive illness on rational decision making concerning assisted
      suicide requests.

PMID- 9538672
TI  - Sertraline effects on dyspnea in patients with obstructive airways disease.
AB  - Dyspnea can have a debilitating effect on psychosocial and physical functioning
      in patients with chronic obstructive airways disease. Previous research has
      suggested that treatment of concomitant mood or anxiety symptoms can improve
      dyspnea and exercise intolerance among patients with respiratory disease. The
      authors report here on a case series of 7 patients with obstructive airways
      disease who reported improvements in dyspnea after sertraline 25-100 mg/day was
      added to their medication regimens. Four of the seven patients did not appear to
      meet syndromal criteria for a mood or anxiety disorder. Subjective improvements
      in dyspnea may have been related to relief of mood or anxiety symptoms or to
      direct effects on central respiratory systems. Controlled studies are needed to
      clarify the potential antidyspneic effects of sertraline.

PMID- 9538673
TI  - Perioperative anxiety and depression in open-heart surgery.
AB  - Eighty patients completed state-anxiety and depression inventories on the day
      before, 7 days after, and 6 months after open-heart surgery. The patients with
      high, moderate, or low anticipatory anxiety still had relatively high, moderate,
      and low anxiety, respectively, in the postoperative period, supporting the linear
      relationship between preoperative and postoperative arousal. Omitting the items
      on somatic-vegetative complaints from the global depression score reveals that
      cardiac surgical patients do not experience significant postoperative changes in
      depression related to cognitive-affective symptoms. The preoperative assessment
      of emotional arousal significantly predicts the level of emotional distress after
      surgery.

PMID- 9538674
TI  - Stiff-man syndrome. Results of interviews and psychologic testing.
AB  - Thirteen patients with stiff-man syndrome (SMS) were studied with the Minnesota
      Multiphasic Personality Inventory (MMPI), the Self-Administered Alcoholism
      Screening Test (SAAST), the State-Trait Anxiety Inventory (STAI) profiles, and by
      telephone interviews. The mean MMPI, SAAST, and STAI were within normal limits;
      however, several patients had abnormal profiles. The results of telephone
      interviews revealed that 8 patients (62%) had been given at least 1 psychiatric
      diagnosis and 4 (31%) abused alcohol or were dependent on it. Two patients had a
      psychiatric diagnosis that preceded the onset of symptoms of SMS. The authors
      hypothesize that SMS patients have a gamma-aminobutyric acid deficiency or
      GABAergic neuron dysfunction that leads to psychiatric symptoms, including
      depression and chemical abuse. Clinicians treating patients with SMS must be
      alert to the possible presence of comorbid psychiatric illnesses in this patient
      population.

PMID- 9538675
TI  - The relationship between irritable bowel syndrome and psychiatric illness. A
      family study.
AB  - Although irritable bowel syndrome (IBS) is a common disorder among
      gastrointestinal clinic outpatients, it continues to be a diagnosis of exclusion.
      In treatment-seeking populations, IBS has been frequently associated with
      psychiatric illness, and this co-occurrence has added to controversy about the
      validity of the IBS diagnosis. This study is a preliminary effort to examine the
      nature of this relationship by using the family study design. The probands
      consisted of 20 patients with IBS and 20 patients who had undergone laproscopic
      cholecystectomy. Their first-degree relatives were interviewed to obtain lifetime
      diagnoses of functional gastrointestinal and psychiatric syndromes. Significantly
      more IBS probands had lifetime psychiatric illness than the cholecystectomy
      probands. The lifetime prevalence of IBS as well as other functional
      gastrointestinal syndromes was not significantly different between the groups of
      relatives. However, significantly more relatives of the IBS probands had lifetime
      psychiatric illness than the relatives of the cholecystectomy probands. Among the
      relatives with functional gastrointestinal disorders, significantly more had
      psychiatric illness. This preliminary study provides support for a relationship
      between IBS and psychiatric illness by the finding of an increased prevalence of
      psychiatric disorders among the relatives of patients who have IBS.

PMID- 9538676
TI  - A prospective multicenter study of competency evaluations by psychiatric
      consultation services.
AB  - Psychiatric consultation for assessment of competency is common but infrequently
      studied. Past studies have used chart reviews. The authors prospectively studied
      88 consecutive psychiatric consultations at 3 centers. Competency evaluation was
      performed to determine whether the patient could 1) sign out of the hospital
      against medical advice (AMA) (N = 16); 2) give informed consent (N = 16); 3) take
      care of him-/herself (N = 33); 4) refuse medical care (N = 24); or 5) deal with
      other matters (N = 12). Patients with a favorable risk-benefit ratio were more
      likely to be seen in consultation compared with those with an unfavorable ratio.
      Patients in whom there was concordance in the assessment of the psychiatric
      consultant and the referring physician (N = 61) were more likely to be male,
      single, to have psychotropics recommended, to sign out AMA, and to be discharged
      from the hospital. Patients in whom there was disagreement between the consultee
      and the consultant merits further study.

PMID- 9538677
TI  - The evaluation of eating and weight symptoms in the general hospital consultation
      setting.
AB  - Eating disorders (ED) in the medically ill population have seldom been studied.
      The objective of this study is to review a series of medical and surgical
      patients referred for psychiatric evaluation for a presumed ED. Between 1982 and
      1990, a series of 65 patients were referred for psychiatric consultation to
      evaluate for an ED. All patients records were reviewed for demographic, medical,
      and psychiatric information, including medical course following the consultation.
      Sixty-three percent of the study population were referred by internal medicine
      services. The most common presenting symptoms were self-induced vomiting (39.1%),
      binge eating (34.4%) and weight loss (31.3%). Bulimia nervosa (n = 21), anorexia
      nervosa (n = 19), and no psychiatric diagnosis (n = 18) were the most frequent
      diagnoses. Record review suggested significant challenges to accurate eating
      disorder diagnoses in patients presenting with primary medical complaints.

PMID- 9538678
TI  - Childhood "screen memories." Are they forgotten?
AB  - In the past few years, much has been written on childhood sexual abuse. However,
      there is an absence of any mention of screen memories. Freud introduced the term
      "screen memory" in 1899. He repeatedly returned to the subject of childhood
      memories and concluded all childhood memories are "screen memories" and as such,
      "show us our earliest years not as they were but as they appeared in later years
      when the memories were recovered." Childhood memories are important in what they
      reveal and what they hide, and most important is the affect, not the event.

PMID- 9538679
TI  - Psychotic depression. An atypical initial presentation of multiple sclerosis.

PMID- 9538680
TI  - A case of chronic factitious disorder presenting as repeated, self-inflicted
      burns.

PMID- 9538681
TI  - Psychiatric comorbidity in HIV and AIDS.

PMID- 9538682
TI  - Depression in HIV-infected persons.

PMID- 9538683
TI  - Erythropoietin and visual hallucinations in patients on dialysis.

PMID- 9538684
TI  - Further psychiatric considerations of glossodynia.

PMID- 9538685
TI  - Steric chaperones.

PMID- 9538686
TI  - A good antisense molecule is hard to find.
AB  - Antisense molecules and ribozymes capture the imagination with their promise of
      rational drug design and exquisite specificity. However, they are far more
      difficult to produce than was originally anticipated, and their ability to
      eliminate the function of a single gene has never been proven. Furthermore, a
      wide variety of unexpected non-antisense effects have come to light. Although
      some of these side effects will almost certainly have clinical value, they make
      it hard to produce drugs that act primarily through true antisense mechanisms and
      complicate the use of antisense compounds as research reagents. To minimize
      unwanted non-antisense effects, investigators are searching for antisense
      compounds and ribozymes whose target sites are particularly vulnerable to attack.
      This is a challenging quest.

PMID- 9538687
TI  - The role of the ribosome-translocon complex in translation and assembly of
      polytopic membrane proteins.
AB  - Newly synthesized polytopic membrane proteins and secretory proteins often share
      the same target membrane as their primary destination, and in some cases, the
      cellular machinery that targets and transfers them into or across the membrane.
      Unlike secretory proteins, which are localized to the external compartment, each
      polytopic membrane protein molecule must be partitioned among the cytoplasm, the
      membrane and the external milieu. How does the ribosome-translocon complex cope
      with the different domains of polytopic membrane proteins?

PMID- 9538688
TI  - A hydrophobic sequence motif common to N-hydroxylating enzymes.

PMID- 9538689
TI  - Tubulin tyrosine ligase: a shared fold with the glutathione synthetase ADP
      forming family.

PMID- 9538690
TI  - Fibroblast growth factor receptors: lessons from the genes.
AB  - The fibroblast growth factor receptors (FGFRs) are a family of transmembrane
      tyrosine kinases involved in signalling via interactions with the family of
      fibroblast growth factors (FGFs). Genetic findings have provided a way of
      dissecting these interactions. Mutations in three members of the FGFR family have
      been found in patients with birth defects involving craniosynostosis (premature
      fusion of the cranial sutures) or skeletal abnormalities. Analyses of the
      spectrum of mutations found predict that many of them will result in ligand
      independent activation of the receptors. Amino acids have also been identified
      that are likely to be important in determining the specificity of FGFR-FGF
      interactions.

PMID- 9538691
TI  - An atlas of serpin conformations.
AB  - The serpins are a family of proteins that inhibit chymotrypsin-like serine
      proteinases, with an unusual mechanism involving a large conformational change
      known as the stressed-->relaxed (S-->R) transition. This article is a guide to
      the known serpin conformations and their biological significance.

PMID- 9538692
TI  - Protein folding in the cytosol: chaperonin-dependent and -independent mechanisms.
AB  - Recent findings suggest that a combination of chaperonin-assisted and unassisted
      mechanisms operate in protein folding in the cytosol. While nascent chain-binding
      chaperones, such as Hsp70, could have a general role in maintaining the folding
      competence of translating polypeptide chains, the contribution of the cylindrical
      chaperonin complexes to overall folding is limited to a subset of aggregation
      sensitive polypeptides. The majority of bacterial proteins are relatively small
      and they are synthesized rapidly and folded independently of the chaperonin GroEL
      in a posttranslational manner. Eukaryotes have a proportionally larger number of
      multi-domain proteins than bacteria. The individual domains of these proteins can
      be folded cotranslationally and sequentially. The use of this mechanism explains
      how large proteins fold independently of a chaperonin and could have been crucial
      in the evolution of a wide array of modular polypeptides in eukaryotes.

PMID- 9538693
TI  - Modularity in the TNF-receptor family.
AB  - Tumour necrosis factor (TNF) receptor family members regulate processes that
      range from cell proliferation to programmed cell death. The extracellular, ligand
      binding domains of these proteins consist of small, cysteine-rich subdomains,
      first observed in the three-dimensional structures of the type I TNF receptor. A
      structure-based alignment of TNFR family members indicates that the extracellular
      domains are constructed primarily of two small polypeptide modules. These modules
      play distinctive structural roles in the architecture of the domains. Analogues
      of at least one of these modules can be found in the domains of other receptors
      and extracellular proteins. Variations in their sequence and order of assembly
      are expected to account for differences in shape, flexibility and ligand
      specificity.

PMID- 9538694
TI  - Mechanistic parallels between DNA replication, recombination and transcription.
AB  - The multiprotein complexes that mediate replication, transcription and homologous
      recombination in eukaryotic cells face many of the same molecular challenges.
      These include the recognition of DNA sites embedded in large chromatinized
      genomes, the denaturation of duplex DNA, and partial dissociation and
      reassociation at different stages of the catalytic cycle. Therefore, it is not
      surprising that several steps in the respective catalytic cycles are strikingly
      similar at the DNA level and may proceed by similar mechanisms. Some of these
      relationships are reviewed here. It is argued that speculation based on such
      'crosspathway' comparisons may be a valuable paradigm for the design of new
      experiments.

PMID- 9538695
TI  - Getting to grips with contraction: the interplay of structure and biochemistry.

PMID- 9538696
TI  - Unusual behavior exhibited by multistranded guanine-rich DNA complexes.
AB  - The structural properties of oligonucleotides containing two different types of G
      rich sequences at the 3'-ends were compared. It is shown that oligonucleotides
      with uninterrupted runs of guanine residues at the 3'-end, e.g., d(T15G12), form
      multistranded structures stabilized by guanine-guanine interactions. The chemical
      and physical properties of these complexes differ from those of the complexes
      formed by oligonucleotides with telomere-like sequences, e.g., d(T15G4T2G4). In
      methylation protection and methylation interference experiments, we found all the
      guanines in complexes formed by d(T15G15) and d(T15G12) to be accessible to
      methylation. Furthermore, the methylated monomers retain the ability to
      polymerize. This contrasts with the inaccessibility of the guanines in
      d(T15G4T2G4) to methylation and the inability of the methylated monomer to form
      supramolecular structures. The stoichiometry of the complexes arising from the
      two types of oligonucleotides also differs. The complexes formed by d(T15G15)
      consist of consecutive integer numbers of DNA strands, whereas complexes formed
      by telomere-like oligonucleotides contain 1, 2, 4, or multiples of four strands.
      Magnesium ions favor formation of high molecular weight complexes by d(T15G15)
      and d(T15G12), but not by d(T15G4T2G4). The d(T15G15) and d(T15G12) complexes
      have very high thermal stability compared with telomeric complexes. However, at
      low temperatures, the thymine bases within the telomeric motif, TTGGGGTTGGGG,
      appear to allow for the formation of stable high-molecular weight species with a
      longer nonguanine portion.

PMID- 9538697
TI  - Derivation of class II force fields. VI. Carbohydrate compounds and anomeric
      effects.
AB  - The methodology for deriving class II force fields has been applied to acetal,
      hemiacetal, and carbohydrate compounds. A set of eighteen model compounds
      containing one or more anomeric centers was selected for generating the quantum
      mechanical energy surface, from which the force field was derived and the
      functional form assessed. The quality of the fit was tested by comparing the
      energy surface predicted by the force field with ab initio results. Structural,
      energetic, and dynamic properties (vibrational frequencies) were analyzed. In
      addition, alpha and beta anomeric equilibrium structures and energies of 2
      methoxytetrahydropyran, 2-deoxyribose, and glucose were computed at the HF/6-31G*
      and higher ab initio levels. These calculations provide test data from molecules
      outside the training set used to derive the force field. The quantum calculations
      were used to assess the ability of the class II force field and two quadratic
      diagonal (class I) force fields, CVFF, and Homans' extension of the AMBER force
      field, to account for the anomeric effects on the structural and energetic
      properties of carbohydrate systems. These class I force fields are unable to
      account for observed structural and energetic trends, exhibiting deviations as
      large as 5 kcal/mol in relative energies. The class II force field, on the other
      hand, is shown to reproduce anomeric structural as well as energetic differences.
      An energy component analysis of this force field shows that the anomeric
      differences are dominated by torsional energies, although coupling terms,
      especially angle/torsion, also make significant contributions (roughly 1 kcal/mol
      in glucose). In addition, the force field accurately accounts for both anomeric
      and exo-anomeric energy differences in 2-methoxytetrahydropyran, and anomeric
      energy differences in 2-deoxyribose and glucose.

PMID- 9538698
TI  - [Guidelines for professional responsibilities of the head nurse in South African
      state hospitals].
AB  - This is a follow-up article on a functional analysis of the post responsibilities
      of the Chief Professional Nurse in South African State hospitals. The purpose of
      this study is to formulate guidelines for the Chief Professional Nurse's post
      responsibilities in State hospitals. The final statements, on which the
      conceptual framework is based, are inferred from the previous justified
      objectives: the exploration and description of the existing job/post descriptions
      of the Chief Professional Nurse, an exploration and description of the different
      role-players' expectations regarding the post/job responsibilities of the Chief
      Professional Nurse, followed by a literature control. The guidelines are
      formulated and it is recommended that they be implemented, followed by the
      testing of various hypotheses to confirm the value of these guidelines.

PMID- 9538699
TI  - Factors associated with pre-eclampsia and quality care of affected teenagers
      during labour within health region H. in Kwa-Zulu Natal.
AB  - This is a descriptive, exploratory study which aimed at identifying the factors
      that are associated with pre-eclampsia in teenagers. The study also aimed at
      assessing the quality of midwifery care during labour in teenagers with pre
      eclampsia so that recommendations can be made based on empirical findings. The
      study was done within Health Region H of KwaZulu-Natal Province in South Africa.
      A structured interview schedule was designed to tap information from pre
      eclamptic teenagers in an attempt to identify factors associated with pre
      eclampsia. A checklist was also designed and administered to assess the care of a
      pre-eclamptic teenager during labour. The study revealed that factors like age,
      nulliparity and socio-economic status were associated with pre-eclampsia. In as
      far as the rest of the factors, there was no relationship as indicated in
      previous studies. The study also revealed that teenagers affected by pre
      eclampsia delayed in attending the antenatal clinic resulting in the control of
      the disease being difficult. In as far as midwifery care, the study revealed that
      psychological and social care, as well as the hygienic state of patients was not
      satisfactory. Based on the findings of the study, it is recommended that health
      education on prevention of pre-eclampsia should be done on an ongoing process,
      while carers for teenage mothers should be given inservice education programmes
      on psychosocial care. The physical environment for maternity units must be
      improved.

PMID- 9538700
TI  - [Study of the learning climate in a nursing college].
AB  - A descriptive survey was undertaken to determine the learning climate with the
      focus on the psychological climate. Questionnaires were distributed amongst
      second, third and fourth year students that follow the Diploma in Nursing Leading
      to Registration as a Nurse (General, Psychiatric, Community) and Midwife. The
      results indicated that a positive learning climate is maintained to a great
      extent in the college and during structured clinical accompaniment. However there
      are some problems which impede maintenance of an optimal learning climate. The
      learning climate in health care units is inadequate. Accompaniment of students by
      tutors realize to a greater extent in the third and fourth years, but second year
      students identified problems in this regard. Second year students are of the
      opinion that their clinical tutors are not adequately available for accompaniment
      while they work in the health care services. Accompaniment by registered nurses
      is inadequate.

PMID- 9538701
TI  - Change management in health services: the South African experience.
AB  - The purpose with this article is to describe the principles of change management
      in health services, as experienced in South Africa to date. The driving forces
      are highlighted, followed by a brief explanation of the three phases in change
      management. The principles and process of change management, as applied to the
      South African health system, are described as perceived by the author. The paper
      was read as an invited presentation at the Commonwealth Nurses Federation's
      General Meeting and workshop on 13 June 1997 in Vancouver, Canada.

PMID- 9538702
TI  - [Ethics in nursing].
AB  - The conclusion reached at the end of this article is that there is a crisis in
      the ethics of nursing and that the focus of the ethics of nursing should be on
      virtues. The reconstruction of a virtue-based ethics in nursing is proposed as a
      solution for the current crisis in the ethics of nursing. With an analysis
      conducted on the ethics of nursing the story is told of an individual nurse
      within nursing in the South African society. Certain concepts to ethics as well
      as the dimensions of ethics in nursing are explained within the narrative of
      nursing. The institutionalisation of ethics of nursing is described based on the
      three ethical traditions that moved from virtues, to responsibility to human
      rights. An analysis of the moral practice in nursing indicates that a crisis in
      the ethics of nursing exist within the last tradition of human rights because of
      the conflict between the rights of the nurse and the patient. Through the
      analysis it becomes clear that no rules, codes or law can ensure moral behaviour.
      The control over moral behaviour should rather be internal than external. If a
      person does not have the virtues he or she does not understands the rules and
      human rights and responsibilities have a different meaning for them.

PMID- 9538703
TI  - An orientation program for nurses in a cardio thoracic intensive care unit.
AB  - The objective of this qualitative, explorative and descriptive study was to
      explore and describe the contents and management of an orientation program for a
      specific cardio thoracic intensive care unit of a specific private hospital. The
      goals of the study were: Conducting a literature review to explore and describe
      the concepts identified in the conceptual framework and thereby lending
      theoretical support to the contents and management of the orientation program. To
      explore and describe the expectations of the learner with regard to the contents
      and management of the orientation program. To explore and describe the
      expectations of the senior professional nursing team with regard to the contents
      and management of the orientation program.

PMID- 9538704
TI  - [Nurses' knowledge of aspects of the trade union system].
AB  - The democratisation of the work place has implications for the nursing profession
      where conflict exists between the registered nurse as employee and professional
      practitioner with related professional-ethical responsibilities, and membership
      of a trade union with access to industrial action. It appears as if trade unions
      have recruited a significant number of nurses as members over the last few years.
      The aim with this research is to determine the knowledge of registered nurses
      with regard to aspects related to trade unions. An exploratory and descriptive
      research design was followed, utilising a structured questionnaire in a survey to
      determine the knowledge of registered nurses on certain aspects related to trade
      unions, within the context of hospitals in Gauteng and in the Free State. The
      study reveals inadequate knowledge of registered nurses regarding aspects related
      to trade unions (average percentage of knowledge is 33.8%) and empowerment
      through education in this regard seems necessary.

PMID- 9538705
TI  - Prediction of nurses' job satisfaction level.
AB  - Indications are that job satisfaction of nurses in South Africa is at a low
      level. The need to determine factors related to this situation prompted a study
      in which an attempt was made to determine whether self-concept (measured by
      Vrey's self-concept Scale) and career orientation scores (determined by means of
      the Career Orientation Inventory (COI) developed by Schein) could predict the
      level of job satisfaction of nurses (measured by means of the Minnesota Job
      Satisfaction Questionnaire (MSQ)). The instruments were applied to 86
      professional nurses employed in an academic (teaching) hospital. The sample was
      divided into a high satisfaction group (N = 46) and a low satisfaction (N = 40)
      group. Hotelling's T2, MANOVA, Stepwise Multiple Regression and discriminant
      analyses were used to analyze the data. Results indicated that the two groups
      differed on several self-concept scales and on one career orientation scale.
      Eighteen per cent of the variance in job satisfaction could be explained by means
      of career orientation and self-concept scores. Sixty seven per cent of the
      respondents were placed in the correct group (in terms of their job satisfaction
      level) using self-concept and career orientation scores.

PMID- 9538706
TI  - [The psychiatric community nurse's experience about her interaction with the
      psychiatric patient].
AB  - The experiences of psychiatric community nurses with regard to their interaction
      with psychiatric patients were explored and described. A qualitative,
      exploratory, descriptive and contextual design was used. Phenomenological semi
      structured interviews were conducted with a purposefully selected sample
      population. Trustworthiness was ensured by using Lincoln & Guba's (1985) model. A
      literature control was conducted as well. Results indicated that healthier
      support is needed for the psychiatric nurse to facilitate therapeutic interaction
      between the psychiatric patient and the community psychiatric nurse.

PMID- 9538707
TI  - The perception of the image of nursing.
AB  - A quantitative research study in the form of a descriptive survey was undertaken
      with the aim of determining the public's perception of the image of nursing at
      the Umtata District of the Eastern Cape Province. Twenty participants were
      selected systematically from queues of patients in the Out Patient department of
      Umtata General Hospital. A semi-structured interview schedule was used the prime
      method of data collection. Data analysis was done by means of a computer software
      package called SAS. The findings revealed that 95% (N = 19) of the respondents
      viewed the nursing profession as a calling whilst only 5% (N = 1) viewed nursing
      as a job. Thirteen factors were identified as contributory to the changing image
      of nursing. Recommendations proposed included the dissemination of nursing
      information in the form of pamphlets, and implementation of health development
      programmes at public gatherings with the aim of increasing public awareness
      regarding new developments in the nursing profession. Training in assertiveness
      was also suggested with the aim of helping nurses express themselves as opposed
      to their tendency to withdraw into subservient roles.

PMID- 9538708
TI  - [The life world of adolescents with mental health problems].
AB  - Adolescents are currently being exposed more and more to the expectations of
      parents, educators, healthworker/helpers and policy makers to meet the demands of
      society and conform with it. The perception arises that adults are not able to
      let the adolescent take responsibility for the HOW of his own life story, despite
      of all the expectations and demands. Under the influence of the postmodern
      approach to science and the narrative therapy it appears that each person is an
      expert of his own life and that each person is responsible for the how and the
      writing and rewriting of his own life story. This means that even the adolescent
      with mental health problems is busy with the writing and rewriting of his life
      story till even unpleasant incidents and experiences can get new meaning. This
      demands from the adolescent with mental health problems to be actively involved
      with his treatment programme while the therapist is a participative observer of
      the therapeutic events. A one sided approach where the therapist's objectives and
      ideals for the adolescent with mental health problems make the difference to the
      treatment is outdated. A alternative approach is suggested where the adolescent
      with mental health problems becomes co-author of his own life story and his
      treatment programme. In this research the researcher aimed to explore and
      describe the HOW of the lifeworld of the adolescent with mental health problems.
      The utilization of the case-study format as research method enabled a in depth,
      holistic description of the lifeworld of the adolescent with mental health
      problems. The implementation of the strategies to ensure trustworthiness, as
      described by Guba were applied to ensure the validity and reliability of this
      study. Focus were especially placed on the application of the strategy of cross
      validation. This implies that multiple data-collection sources, different
      experts, theories and respondents were utilized in the exploration of the
      lifeworld of the adolescent with mental health problems before this lifeworld was
      describe in depth. The researcher makes a few conclusions and based on this made
      recommendations for application in practice, education and research.

PMID- 9538709
TI  - Professional progress and potential pitfalls.

PMID- 9538711
TI  - Sensoristrain: an exploration of nursing interventions in the context of the
      Neuman systems theory.
AB  - Defining what nurses do and why has been the endeavour of many researchers, both
      academic and clinical. Nursing interventions are a fundamental component of
      nursing practice and a focus on accountability means that nurses must be able to
      justify their actions. The sensoristrain experience of intensive care patients is
      widely acknowledged in nursing literature, though without the use of the word
      'sensoristrain'. The aim in this paper is to place patients, their experience and
      the role of nurses within the practical framework of a suitable nursing theory
      which will elucidate and guide everyday practice in preventing and alleviating
      the causes (stressors), symptoms (reactions) and emotional aftermatch. Nursing
      interventions appropriate for the three modalities of intervention elucidated by
      the Neuman systems theory have been outlined, paralleled by a discussion of how
      these could relate to the three dimensions of nursing care: comfort care; knowing
      the patient; and the therapeutic presence of the nurse. Nurses must use each
      opportunity to advance practice through emphasizing the value of nursing in
      today's cost-conscious health care climate. In order to do this, and to ensure
      nurses' continued presence at the bedside, clear articulation of the contribution
      of nursing interventions to improved patient outcomes is essential.

PMID- 9538710
TI  - Follow-up services and the development of a clinical nurse specialist in
      intensive care.
AB  - There is little information available regarding quality of life following
      critical illness. The consequences of a stay in an intensive care unit (ICU) can
      result in considerable psychological and physical morbidity. At the Homerton
      Hospital, London, UK an intensive care follow-up outpatient clinic was
      established to ascertain patients' experiences after discharge from the ICU. This
      exploratory study examines narrative data collected from 26 patients by means of
      unstructured client-led interviews. Themes are derived that have implications for
      staff, patients and relatives. The findings suggest that patients experience a
      variety of psychological and physical symptoms. Patients experienced vivid
      dreams, flashbacks, relocation and convalescent stress as well as profound
      tiredness and weakness. These are consistent with previous research findings. New
      themes were identified which suggest that mood changes, inability to cope, the
      need to talk about their ICU experience and indistinct memories of the ICU made
      recovery at home difficult for both the patients and their families. As a result
      of these findings, the role of a clinical nurse specialist has developed in order
      to improve liaison between and within departments, the hospital and the
      community. Future research will aim to focus on the role of the critical
      care/community liaison clinical nurse specialist and in improving outcomes
      through the use of action research.

PMID- 9538712
TI  - The significance of statistical significance.
AB  - Currently, much nursing practice is based on limited evidence, for example, small
      scale research, case studies and clinical experience. In a mature science this
      would be undesirable, but nursing is in the early stages of development as a
      science, and many of its practices depend on relatively informal knowledge. To
      encourage the spread of potentially valuable ideas, nurses must be willing to
      share their clinical experience and journal editors should consider publishing
      this information. High-quality research is essential to the long-term development
      of 'evidence-based practice', but it is crucial at the present stage of nursing
      science that we do not become too concerned with perfect research methodology at
      the expense of good ideas. This particularly applies to tests of statistical
      significance. If we accept only information that has demonstrated statistical
      significance, we risk the dismissal of qualitative research and other information
      which may be extremely valuable but which have not yet been fully investigated.
      The aim of this paper is to convince practitioners and journal editors that
      statistical significance is not the only way to judge clinical importance and to
      suggest that decisions on what should be submitted and accepted for publication
      should be based on potential clinical relevance as well as statistical analysis.

PMID- 9538713
TI  - Core body temperature measurement: a comparison of axilla, tympanic membrane and
      pulmonary artery blood temperature.
AB  - This research study was undertaken to examine the relationship between pulmonary
      artery blood temperature (regarded as the 'gold standard' measurement for core
      body temperature), axilla temperature using the Tempa.DOT Ax chemical thermometer
      and tympanic membrane temperature using the Diatek 9000 InstaTemp thermometer.
      Sixty adult intensive care patients had their temperatures monitored. A single
      set of five simultaneous temperatures, i.e. left and right axilla, left and right
      tympanic membrane (TM), and pulmonary artery (PA) blood were recorded. The mean
      difference between left and right TM temperatures was 0.58 degree C, and although
      both were moderately well correlated with PA temperature (r = 0.63 and 0.78,
      respectively) the mean differences between the two sites were clinically
      significant (0.85 degree C and 0.94 degree C, respectively). The range of
      differences between the sites was significant. Plotting limits of agreement
      showed that both left and right TM temperatures may be up to 1.2 degrees C above
      or 1.3 degrees C below PA blood temperature: a clinically unacceptable range. In
      particular, large temperature differences were recorded when patients were lying
      with one side of their head to a pillow. Fan therapy directed to the head was not
      found to affect these differences significantly. The mean difference between left
      and right axilla temperatures was 0.36 degree C, and although both were modestly
      correlated with PA temperature (r = 0.48 and 0.53, respectively) the mean
      differences between the two sites were clinically significant (0.47 degree C and
      0.50 degree C, respectively). The range of differences between the sites was
      particularly significant. Plotting limits of agreement showed that both left and
      right axilla temperatures may be up to 1.2 degrees C above or 1.6 degrees C below
      PA blood temperature: a clinically unacceptable range. Because the range of
      temperature differences found between PA blood and the other sites was so great,
      it is concluded that neither the chemical axilla thermometer nor the tympanic
      membrane thermometer used in this study are clinically reliable tools for adult
      intensive care patients.

PMID- 9538714
TI  - Using research to find the effects of process-oriented educational assessment in
      critical care nursing practice.
AB  - This 1-year study was undertaken in the southeast of England to investigate
      whether a process-oriented educational assessment procedure was sustainable,
      following research in a sample of five critical care environments. Data were
      derived from clinical practice supervisors and students in each of two
      consecutive post-registration cohorts, selected from the following areas:
      intensive and coronary care units; neonatal nursing; medical-surgical units;
      operating theatres; and accident and emergency departments. The existing measure
      and then a modified assessment measure for resuscitation ability, were used to
      evaluate the effect of educational assessment in clinical settings. Data were
      collected using questionnaires with cohort 1 before and cohort 2 after
      introduction of an assessment grid developed by the course team based on data
      from focus group discussions during the clinical supervisors' workshops. The
      findings indicated that the descriptors of levels of attainment generated by the
      students and supervisors were in accord with Benner's descriptors (this had
      increased by phase 2 of the research). Students and supervisors considered that
      the assessment process increased their critical thinking abilities, but that
      finding time for supervision and assessment was difficult. Future work will focus
      on the development of a generic grid with criteria that can be used to guide
      assessment of any practice experience.

PMID- 9538715
TI  - Dependency scoring in a critical care area: a direct nursing assessment method.
AB  - The evaluation of dependency in a critical care area can be a difficult process.
      Often, dependency scoring systems involve time-consuming data completion and
      collection. The innovative method of dependency scoring described here uses
      bedside nurses' own assessment of patient needs to provide an accurate and usable
      scoring system based upon nursing process documentation. It may also provide a
      method by which dependency may be calculated using computerized systems.

PMID- 9538716
TI  - Benefits of an electronic clinical information system: an intensive care nursing
      perspective.
AB  - Due to advancements in surgery, medicine and equipment, the modern intensive care
      unit (ICU) patient necessitates the recording of vast amounts of data. The
      management of these data is increasingly impinging on nursing time. A review of
      the literature describes the potential benefits of using a clinical information
      system (CIS) to record and save data electronically rather than transcribing it
      onto conventional charts. Commercial systems that can perform these tasks are
      available but have severe financial implications in terms of initial costs,
      maintenance and upgrading. Work is continuing at Killingbeck Hospital on a
      project developing and introducing a CIS into intensive care using standard
      hardware, software and programming tools thus minimizing these costs.

PMID- 9538717
TI  - Physiological changes occurring with positive pressure ventilation: Part one.
AB  - Critically ill patients requiring mechanical ventilation are subject to a variety
      of complications and adverse effects associated with positive pressure
      ventilation. An awareness of the major physiological effects is important, as
      recognition, prevention and appropriate treatment of complications is critical to
      optimizing patient outcome. Pierson (1990) suggests that complications due to
      ventilation occur with greater frequency than is generally appreciated, and can
      be a response to suboptimal ventilatory management as a result of poor
      communication and lack of understanding. This may also adversely affect patient
      comfort, morbidity and outcome. This can be avoided by improved knowledge of both
      the function of ventilators and the adverse effects associated with mechanical
      ventilation. Intensive care nurses face the challenge of caring not only for
      critically ill patients but also for complex machinery. To improve the delivery
      of care to the patients, an understanding of the machines and their adverse
      effects is essential. This increases the nurses' confidence and allows them to
      focus on the patients and associated problems while maintaining safe and informed
      care. With the introduction of mechanical ventilation, major physiological
      changes occur, for example airway resistance and intrathoracic pressures are
      increased and lung mechanics are altered. The following article provides
      explanation as to how and why mechanical ventilation produces these changes, and
      highlights areas where they occur.

PMID- 9538718
TI  - Teicoplanin (Targocid, Hoechst Marion Roussel): a new glycopeptide antibiotic.
AB  - The glycopeptides are important antibiotics in the management of Staphylococcal
      infections. Teicoplanin, the latest member of the group, may offer some
      advantages over vancomycin, the workhorse drug, which has retained its importance
      in the presence of increasing major resistance to other antistaphylococcal
      agents.

PMID- 9538720
TI  - [Post-traumatic stress syndrome: the invisible wound].

PMID- 9538721
TI  - [Client-oriented care: from authority to service].

PMID- 9538722
TI  - [Education for practice: Robinson and the learning workshop].

PMID- 9538723
TI  - [A hospital for Gambia. Involvement in the service of the people].

PMID- 9538724
TI  - [Gender-specific upbringing: typical boy, typical girl].

PMID- 9538725
TI  - [Competent care for our small patients].

PMID- 9538726
TI  - [The sun--also in old age homes].

PMID- 9538727
TI  - [Does one learn to love?].

PMID- 9538728
TI  - [Long-term care of psychiatric patients. An interdisciplinary experience].

PMID- 9538729
TI  - [Diagnosis: leukemia. The worst of all is the uncertainty].

PMID- 9538730
TI  - [Reflections on the development of the nursing profession. The practice of care
      at the dawn of the year 2000].

PMID- 9538731
TI  - [Reflections on grief. Personal development in the service of others].

PMID- 9538732
TI  - [Care of the aged. Talking openly about death].

PMID- 9538734
TI  - [The rediscovery of writing. Starting a relationship with one's self].

PMID- 9538735
TI  - One more thing....

PMID- 9538736
TI  - Florida advanced practice at a glance.

PMID- 9538737
TI  - Truth in labeling.

PMID- 9538738
TI  - Nursing today's college student.

PMID- 9538739
TI  - Unannounced JCAHO survey.

PMID- 9538740
TI  - Nurses step in to reduce black infant mortality in New Jersey.

PMID- 9538741
TI  - Nurses serving humanity- and each other. Interview by Rita Miller.

PMID- 9538742
TI  - Mom knows best.

PMID- 9538743
TI  - Manage resources, lead people.

PMID- 9538744
TI  - The battle against ignorance.

PMID- 9538745
TI  - Acute care NPs: who are they?

PMID- 9538746
TI  - Erectile dysfunction.

PMID- 9538747
TI  - Rattlesnake bite--treatment or mistreatment?

PMID- 9538748
TI  - Caring made a difference.

PMID- 9538749
TI  - Where confidence comes from.

PMID- 9538750
TI  - Nurses in collaborative practice: a local perspective.

PMID- 9538751
TI  - Earaches and antibiotics.

PMID- 9538752
TI  - Each one, reach one!

PMID- 9538753
TI  - Women and heart disease.

PMID- 9538754
TI  - Community health nursing in a university setting.

PMID- 9538755
TI  - Everlasting tribute.

PMID- 9538756
TI  - Complementary care: old therapy with a new twist.

PMID- 9538757
TI  - The arrival of the Internet.

PMID- 9538758
TI  - Screening the screeners.

PMID- 9538759
TI  - High hopes for new deal.

PMID- 9538760
TI  - Time for celebration.

PMID- 9538761
TI  - A return to a caring service.

PMID- 9538763
TI  - Regulation review. Looking at the nuts and bolts.

PMID- 9538762
TI  - Merger mania.

PMID- 9538764
TI  - Standards for patients with renal failure.
AB  - A recent report aims to improve the quality of care for adults with serious
      kidney failure. An expert committee sets out the recommended standards of care
      for patients who may need dialysis, transplantation or other treatment for renal
      disease. This report summarises their work.

PMID- 9538765
TI  - Assessing primary nursing in mental health.
AB  - One of the most important advantages of primary nursing is the consistency and
      continuity of care which it is said to promote. In the study described here, the
      authors examine the extent to which this continuity of care is achieved when
      primary nursing is used and recommend that this should be audited in all clinical
      areas.

PMID- 9538766
TI  - Occupational standards and professional development.
AB  - Last week, Edwards (1998) examined the use of occupational standards in
      developing the surgical assistant's role. In this article the author describes
      the preliminary findings from a separate study to assess competency in
      professional development programmes.

PMID- 9538767
TI  - Psoriasis: a review of present and future management.
AB  - Psoriasis is a chronic skin condition prevalent in a significant minority of the
      population. Its cause is unknown and effective treatments are elusive. In this
      article, the authors examine the impact of the disease on patients' lives and
      describe how unproven treatments make skilled nursing essential for people with
      such a challenging and disabling disease.

PMID- 9538768
TI  - Cancer: altered body image.

PMID- 9538769
TI  - Getting enthusiastic about policy.

PMID- 9538770
TI  - When life-saving treatment is futile.

PMID- 9538771
TI  - Career pathways for children's nurses.

PMID- 9538772
TI  - Nursing children in a range of hospital settings.

PMID- 9538773
TI  - Clean-catch versus urine collection pads: a prospective trial.
AB  - Two methods for collecting urine samples from very young children were compared
      in a paediatric ward of a busy district general hospital. Samples collected using
      urine collection pads were compared to the standard clean-catch method using
      sterile foil bowls. No significant differences were observed in the outcome of
      tests from samples collected by the two methods over the course of a short nurse
      led trial, and the hospital has adopted the urine collection pad for routine
      paediatric UTI sampling.

PMID- 9538774
TI  - Neonatal nursing in the community.

PMID- 9538775
TI  - SIDS: challenging present nursing practice.

PMID- 9538776
TI  - Empowerment: family-centred care.
AB  - The major findings from interviews with qualified children's nurses, analysed
      using a grounded theory approach, were that children's nurses have the necessary
      theoretical knowledge to empower families, but they require educational and
      training opportunities in family empowerment. It was also established that a
      working environment that promotes its translation into everyday practice and
      supports them in an empowering model of care for children and families is
      necessary.

PMID- 9538777
TI  - Breastfeeding guidelines for paediatric units. Society of Paediatric Nursing of
      the Royal College of Nursing.

PMID- 9538778
TI  - [Patients' legal position].

PMID- 9538779
TI  - [Relatives ensure influence].

PMID- 9538781
TI  - [On a social odyssey in Brixton].

PMID- 9538780
TI  - [Legislation ignored for aged in elderly care].

PMID- 9538782
TI  - [Completion of new wage system in communities and districts].

PMID- 9538783
TI  - [Report from RISL '98 (Delegates Meeting in Nursing Students' National League)].

PMID- 9538784
TI  - [Study environment in clinical practice].

PMID- 9538785
TI  - [Social service].

PMID- 9538786
TI  - [Children with migraine--can one die from a headache?].

PMID- 9538787
TI  - [Children with migraine--co-responsibility for treatment].

PMID- 9538788
TI  - [Nursing--resources: quality depends on us ourselves].

PMID- 9538790
TI  - [We wonder about it too].

PMID- 9538789
TI  - [Oresund accident examined again].

PMID- 9538791
TI  - [Psychological work environment--problem solving without answers. Interview by
      Soren Palsbo].

PMID- 9538792
TI  - [Psychological work environment--we do not always need to agree. Interview by
      Claus Leick].

PMID- 9538793
TI  - [Psychological work environment--personnel gets stuck. Interview by Claus Leick].

PMID- 9538794
TI  - [Psychological work environment--good workplaces can ensure quality. Interview by
      Claus Leick].

PMID- 9538795
TI  - [Discount-drop].

PMID- 9538796
TI  - [Programmed death].

PMID- 9538797
TI  - [A blot on the health care system].

PMID- 9538798
TI  - [Nursing story: Axel is bleeding].

PMID- 9538799
TI  - [Guidelines on drug administration and patient self administration of drugs.
      Sundhedsstyrelsen (Health Administration)].

PMID- 9538800
TI  - [Professional practice: school students in the hospital].

PMID- 9538801
TI  - [Belated attempt to solve nursing shortage].

PMID- 9538802
TI  - [Discrimination against 18-year-olds in the school health service].

PMID- 9538803
TI  - [Not serious about cash support].

PMID- 9538805
TI  - [Team work and work distribution in the hospital].

PMID- 9538804
TI  - [Nurses do not have obligatory service].

PMID- 9538806
TI  - [Personnel shortage--engineered health crisis?].

PMID- 9538807
TI  - [Personnel shortage--the big trip down. Interview by Erik Dale].

PMID- 9538808
TI  - [Personnel shortage--a long half year and new roots. Interview by Tordis Lovise
      Bersas].

PMID- 9538809
TI  - [Quality of life].

PMID- 9538811
TI  - [Basic education--rotation service and clinical examination!].

PMID- 9538810
TI  - [Closeup: Laila Davoy, president of Norwegian Nursing Association. First wage
      scale settlement, just a re-election problem. Interview by Bjorn Arild Ostby].

PMID- 9538812
TI  - [My workplace: Aker Hospital, Psychiatric Division, Section Gaustad. At home
      behind locked doors. Interview by Kari Ann Aase].

PMID- 9538813
TI  - [From bygone days--Norwegian women--an overview of their position and living
      conditions in the age 1814-1914].

PMID- 9538814
TI  - [Manual dexterity--touch me and I will tell you who you are. Interview by Marit
      Fonn].

PMID- 9538815
TI  - [Psychiatry--from scapegoat to main therapy. Interview by Anne Vik Pettersson].

PMID- 9538816
TI  - [Psychiatry--distance saved me. Interview by Anne Vik Pettersson].

PMID- 9538818
TI  - [Monks against AIDS].

PMID- 9538817
TI  - [Nutrition--free access to fat and cream].

PMID- 9538819
TI  - [Nursing in London].

PMID- 9538820
TI  - [Education--alternative student practice].

PMID- 9538821
TI  - [Health station--on my or your terms?].

PMID- 9538822
TI  - [Pain treatment--women with hysterectomy suffer more than necessary].

PMID- 9538823
TI  - [Can a nurse have ring in the nose?].

PMID- 9538824
TI  - [School girls' vulnerability].

PMID- 9538825
TI  - [Health care employees see worsening working conditions].

PMID- 9538826
TI  - [At the second round in midwives' goals].

PMID- 9538827
TI  - [A blow for children's violation].

PMID- 9538828
TI  - [Doubt in one's own knowledge frequently awakens interest in nursing theories].

PMID- 9538829
TI  - [We didn't get educated to work unethically and undignified].

PMID- 9538830
TI  - [DN article (Dagens Nyheter) does not correspond to visions].

PMID- 9538831
TI  - [Let quasi-markets take over health and nursing care].

PMID- 9538832
TI  - [Our association in modern dress].

PMID- 9538833
TI  - [Fistula hospital gives new life to young women].

PMID- 9538834
TI  - [Environment in the center when new hospital is built. Interview by Jan
      Thomasson].

PMID- 9538835
TI  - [Many nurses can give prescription advice].

PMID- 9538836
TI  - [Women's violation offense introduced in Criminal Code].

PMID- 9538837
TI  - [Health-giving factors are central here].

PMID- 9538838
TI  - [Continued boycott against Nestle].

PMID- 9538839
TI  - [When does a fetus begin to feel pain?].

PMID- 9538841
TI  - 98th Annual meeting of the American Roentgen Ray Society, San Francisco,
      California, USA. April 26-May 1, 1998. Abstracts.

PMID- 9538840
TI  - [Syringe exchange continues].

PMID- 9538842
TI  - Experimental Biology 98. San Francisco, California, USA. April 18-22, 1998. Part
      I, Abstracts.

PMID- 9538843
TI  - Experimental Biology 98. San Francisco, California, USA. April 18-22, 1998. Part
      II, Abstracts.

PMID- 9538844
TI  - The Association for Research in Vision and Ophthalmology (ARVO) annual meeting.
      Fort Lauderdale, Florida, USA. May 10-15, 1998. Abstracts.

PMID- 9538845
TI  - 17th Joint meeting of the British Endocrine Societies. Edinburg, 23-25 March
      1998. Abstracts.

PMID- 9538846
TI  - A GOFM and damn proud of it!

PMID- 9538847
TI  - Can CJD be transmitted through the blood supply?

PMID- 9538848
TI  - Can CJD be transmitted through the blood supply.

PMID- 9538849
TI  - Jehovah's Witnesses and blood transfusions.

PMID- 9538850
TI  - The Class of 1989 and physician supply in Canada.
AB  - BACKGROUND: "The Class of 1989" is a study of 1722 people who were awarded an MD
      degree by a Canadian university in 1989. This paper reports on migration,
      specialty choices and patterns of post-MD training in order to assess the
      contribution of the graduating cohort to the physician workforce of Canada.
      METHODS: A longitudinal study was conducted over 7 years after graduation to
      trace the current location, the post-MD training history and the professional
      activity of the graduating cohort. Several medical professional and educational
      associations in Canada and the United States provided year-by-year information on
      field and location of post-MD training, certification achieved, whether in
      practice and location of practice through to spring 1996. Information from all
      sources was linked to a list of 1989 medical school graduates. RESULTS: From
      entry to medical school through to 7 years after graduation the cohort was
      diminished by about 16%. The main reason for loss was migration to other
      countries: 193 graduates (11.2%) were outside Canada in 1995-96. Internal
      migration was extensive also; for example, by 1995-96 relatively few of the
      graduates were located in Newfoundland or Saskatchewan. Of the 1516 graduates
      active in Canada in 1995-96, 878 (57.9%) were in general practice/family
      medicine, and only 638 (42.1%) were practising or training in a specialty.
      INTERPRETATION: The "yield" of the Class of 1989 for Canada's physician workforce
      is insufficient to meet annual physician inflows from Canadian sources to serve
      population growth and to replace retiring or emigrating physicians. As output
      from Canada's medical schools drops even further, the gap between requirements
      and supply will grow even wider.

PMID- 9538851
TI  - The Class of 1989 and post-MD training.
AB  - BACKGROUND: "The Class of 1989" is a longitudinal study of 1722 people who were
      awarded an MD degree by a Canadian university in 1989. This paper reports on the
      details of their post-MD training up to spring 1996. METHODS: Several medical
      professional and educational associations in Canada and the United States
      provided year-by-year information on field and location of post-MD training,
      certification achieved, whether in practice and location of practice through to
      spring 1996. Information from all sources was linked to a list of 1989 medical
      school graduates. RESULTS: Of the 1722 graduates 57 (3.3%) never entered post-MD
      training in Canada; 147 (8.5%) did 1 or more years of training in the United
      States. A total of 222 graduates (12.9%) took a break of at least 1 year from
      training, and 301 (17.5%) changed their choice of field or specialty after
      starting training. Substantial numbers took 1 or more years longer to complete
      training than would be expected based on the prescribed length of the training
      program chosen. The field or specialty choices of the cohort produced a
      generalist:specialist ratio of 58:42. The final numbers in several fields
      depended heavily on trainees changing their initial career choice.
      INTERPRETATION: The data point out widely differing and often very long lead
      times from start to completion of training. Since 1993, changes to licensure
      requirements have reduced opportunities for recent graduating cohorts to delay
      final career choices, take a break in training, prolong training or change
      initial career choices. Rigidities in the post-1993 training environment point to
      the emergence of a number of serious problems, such as dissatisfaction and high
      anxiety levels among residents, licensing authorities being faced with people who
      have not completed a training program to certification, and insufficient
      provision of positions for post-MD training because of underestimates of the time
      needed to complete training programs. The insights gained from this study lead to
      the recognition that planning the specialty distribution of the physician
      workforce is highly complex and difficult.

PMID- 9538852
TI  - High-billing general practitioners and family physicians in Ontario: how do they
      do it? An analysis of practice patterns of GP/FPs with annual billings over
      $400,000.
AB  - BACKGROUND: To better understand the reasons why some fee-for-service physicians
      have high billing levels, the authors compared the practice and demographic
      characteristics of general practitioners and family physicians (GP/FPs) who
      submitted over $400,000 in annual Ontario Health Insurance Plan (OHIP) fee-for
      service claims in 1994-95 with those of GP/FPs who billed between $35,000 and
      $400,000. METHODS: The authors describe the OHIP billing and physician
      characteristic data for fiscal year 1994-95. They used multivariate logistic
      regression to determine factors independently associated with high billing
      status. RESULTS: A total of 219 GP/FPs (2.5% of the GP/FPs in Ontario) billed
      over $400,000 in 1994-95. Of these, 14 had billing patterns similar to those of
      specialists, and 27 billed predominantly for diagnostic and therapeutic
      procedures (particularly physiotherapy). The remaining 178 (81.3%) billed for a
      mix of services similar to that of other GP/FPs but on average had 2.6 times the
      volume of patient assessments and a greater share of their total billings derived
      from diagnostic and therapeutic procedures (9.1% v. 5.6%). Multivariate analysis
      indicated that these high-volume GP/FPs were less likely than GP/FPs who billed
      between $35,000 and $400,000 to be 60 years of age or older (odds ratio [OR]
      0.09, p < 0.05) and female (OR 0.21) and were more likely to be foreign graduates
      (OR 1.85) and practising in a region with low physician supply (OR 0.45 for each
      increase of 1 physician per 1000 population). Metropolitan Toronto was an outlier
      to the latter relation and was more likely to have high-volume GP/FPs (OR 16.89).
      INTERPRETATION: High-billing GP/FPs attained their high billing levels by
      maintaining large numbers of patient visits and by performing procedures. Further
      research is needed to determine the time spent per patient and the quality of
      care delivered by these physicians as well as the appropriateness of the
      procedures that they perform.

PMID- 9538853
TI  - Fee code creep among general practitioners and family physicians in Ontario: why
      does the ratio of intermediate to minor assessments keep climbing?
AB  - BACKGROUND: "Fee code creep" is the increasing tendency of primary care
      physicians in Ontario to bill for more intermediate than minor assessments over
      time. The authors examine the extent and nature of fee code creep and describe
      physician characteristics associated with the changes. METHODS: A cross-sectional
      and longitudinal analysis of Ontario Health Insurance Plan billing and physician
      characteristic data was conducted for fee-for-service general practitioners and
      family physicians (GP/FPs) in Ontario. The ratio of intermediate to minor
      assessments (I-M ratio) was determined for the period 1978-79 to 1994-95, and the
      relation of various physician characteristics to high ratios was tested with
      bivariate and multivariate analysis. RESULTS: The I-M ratio rose 10-fold, from
      0.3 in 1978-79 to 2.9 in 1994-95. Although the I-M ratio was higher for older
      patients and young children, changes in population age profile over time did not
      account for any of the increase. The median ratio varied widely among groups of
      physicians: urban physicians had higher ratios than rural ones (3.9 v. 3.0, p <
      0.05), and recent graduates had higher ratios than physicians 60 years of age or
      older (5.1 v. 2.9, p < 0.05). The I-M ratio was inversely related to number of
      visits; physicians billing for fewer than 5000 visits had a median ratio of 4.2,
      whereas those billing for 20,000 visits or more had a median ratio of 1.6.
      INTERPRETATION: Fee code creep has contributed to expenditure growth in Ontario.
      This phenomenon was related to both an increase in I-M ratio over time among
      physicians practising throughout the study period and an influx of new physicians
      billing at a higher ratio. Creep was not the result of aging of the population.

PMID- 9538854
TI  - New bottles, same old wine: right and wrong on physician supply.

PMID- 9538855
TI  - Practice patterns and billing patterns: let's be frank.

PMID- 9538856
TI  - Hypodermic needles in the neuropathic foot of a patient with diabetes.
AB  - A 54-year-old woman with insulin-dependent diabetes mellitus, diabetic
      neuropathy, neuropathic arthropathy of the feet and a plantar ulcer underwent
      plain radiography, which showed 2 clipped-off hypodermic needles, of which she
      had been unaware, in the soft tissue of one foot. This previously unreported
      complication is clinically instructive in that it demonstrates the importance of
      counselling patients about the protection of insensitive extremities. This case
      also has public health implications, suggesting as it does that the still-common
      practice of breaking hypodermic needles before disposal should be strongly
      discouraged.

PMID- 9538857
TI  - Folic acid fortification: what does it mean for patients and physicians?

PMID- 9538858
TI  - On the trail of Leonardo.
AB  - A night course taken almost 25 years ago sparked an interest in Leonardo da Vinci
      that has become a passion for a London, Ont., neurosurgeon. Dr. Rolando Del
      Maestro now boasts one of the largest collections of da Vinci artifacts in North
      America.

PMID- 9538859
TI  - Why did 12 infants die? Winnipeg's endless inquest seeks answers.
AB  - Canada's longest running inquest will wrap up in Winnipeg in September. Although
      the judge conducting it will be answering many questions, one of the key ones is
      the most simple: Should a province the size of Manitoba operate a program as
      sophisticated as pediatric cardiac surgery?

PMID- 9538860
TI  - For the Class of'98, the real-world education is about to begin.
AB  - In their 4 short years in medical school, members of the Class of '98 have
      witnessed massive changes within the health care system. These are going to have
      a direct, and often negative, impact on the way they practise. Despite this,
      members of this group can't wait to become full-fledged members of the medical
      profession.

PMID- 9538861
TI  - Plasmodium gallinaceum: fluorescent staining of zygotes and ookinetes to study
      malaria parasites in mosquito.
AB  - We have developed a fluorescent labeling procedure for staining the mosquito
      stages of Plasmodium gallinaceum. PKH26, a lipophilic dye, is efficiently and
      permanently incorporated into the membranes of zygotes and ookinetes. Stained
      zygotes undergo normal development into ookinetes; the stain does not interfere
      with ookinete mobility or ability to adhere to the mosquito midgut lumen. Stained
      zygotes and ookinetes are comparable to untreated parasites in their ability to
      give rise to oocysts when fed to mosquitoes. This technique can be used to study
      the development of Plasmodium parasites in the complex cellular environment of
      the mosquito midgut after a blood meal. It may also be adapted to study other
      parasite-vector interactions.

PMID- 9538862
TI  - Fasciola hepatica: characterization and cloning of the major cathepsin B protease
      secreted by newly excysted juvenile liver fluke.
AB  - Proteolytic activity present in the excreted/secreted (ES) material of newly
      excysted juvenile (NEJ) Fasciola hepatica was biochemically analyzed. By gelatin
      substrate SDS-PAGE, only one region of activity was observed in the NEJ ES
      material at a molecular mass of 29 kDa. Both the secreted cathepsin L from adult
      fluke and the 29-kDa proteolytic activity of NEJ ES show a common pH optimum of
      7.5, a cysteine protease inhibition profile, and preference for the N
      benzyloxycarbonyl (Z)-Phe-Arg-NHMec fluorogenic substrate over Z-Arg-Arg-NHMec
      and Z-Arg-NHMec. In vitro analysis revealed that the NEJ protease activity
      digested sheep immunoglobulin heavy chain and bovine serum albumin but not bovine
      hemoglobin. Amino-terminal protein sequence analysis of the 29-kDa NEJ protease
      band revealed two sequences with homology to the cathepsin B family of proteases.
      Using degenerate oligonucleotides designed from the N-terminal sequence, reverse
      transcriptase polymerase chain reaction with NEJ RNA amplified a cDNA sequence
      encoding the first 236 amino acids of mature cathepsin B. Using this cDNA
      fragment an overlapping cDNA was isolated from a LambadaZAP cDNA library
      constructed with poly(A)+ RNA from immature 5-week-old liver fluke. Together with
      the N-terminal sequence, these cDNAs predict a mature cathepsin B sequence of 254
      amino acids which shows 48-51% sequence identity to mammalian and Schistosoma
      mansoni cathepsin B. We conclude that, in contrast to the major proteases
      released by adult fluke, the major secreted protease of NEJ of F. hepatica is of
      the cathepsin B class.

PMID- 9538863
TI  - Plasmodium falciparum: asexual erythrocytic stages synthesize two structurally
      distinct free and protein-bound glycosylphosphatidylinositols in a maturation
      dependent manner.
AB  - Glycosylphosphatidylinositols represent the predominant class of glycolipids
      synthesized by the asexual, intraerythrocytic stages of Plasmodium falciparum.
      These glycolipids have been implicated as malarial toxins involved in parasite
      induced release of cytokines, such as tumor necrosis factor-alpha and interleukin
      1. Two potential glycosylphosphatidylinositol membrane-anchor precursors with the
      structures ethanolamine phosphate (mannose-alpha 1,2)mannose-alpha 1,2-mannose
      alpha 1,6-mannose-alpha 1,4-glucosamine-inositol(acyl)phosphate diacylglycerol
      (P.f.alpha) and ethanolamine-phosphate-mannose-alpha 1,2-mannose-alpha 1,6
      mannose-alpha 1,4-glucosamine-inositol(acyl)phosphate diacylglycerol (P.f.beta)
      have been described in P. falciparum. Only one (P.f.alpha) has been demonstrated
      to serve as an anchor for merozoite surface protein-1 and merozoite surface
      protein-2. In this report we present data showing that asexual, intraerythrocytic
      stages of P. falciparum use both glycosylphosphatidylinositols to anchor
      proteins. The synthesis of the two glycosylphosphatidylinositol membrane anchor
      precursors and the protein-bound glycosylphosphatidylinositol anchors is tightly
      regulated and varies throughout the intraerythrocytic development of the asexual
      stages of P. falciparum. The glycosylphosphatidylinositol membrane-anchor
      precursor P.f.beta is synthesized and transferred to protein predominantly in
      trophozoite stages (about 30 h).

PMID- 9538864
TI  - Brugia malayi: resistance of cuticular lipids to oxidant-induced damage and
      detection of alpha-tocopherol in the neutral lipid fraction.
AB  - We have examined the susceptibility of cuticular membrane lipids of Brugia malayi
      to oxidants generated in vitro. Live parasites as well as extracted cuticular
      lipids were treated with hydrogen peroxide and hypochlorous acid and the extent
      of lipid peroxidation was quantified. The cuticular membranes of B. malayi were
      found to be resistant to lipid peroxidation at hydrogen peroxide concentrations
      which were lethal to the organism. This resistance was partly due to the
      inherently low unsaturation indices of the fatty acyl residues, but complete
      protection was afforded by lipid-soluble antioxidants present in the neutral
      lipid fraction of the parasites. We have identified alpha-tocopherol as a major
      antioxidant present in both adult and microfilarial B. malayi. In addition, we
      report that although hypochlorous acid chemically modifies isolated parasite
      lipids, the latter do not appear to be the primary substrate for the oxidant in
      live worms. The data are discussed in terms of the susceptibility of B. malayi to
      products of the respiratory burst from activated myeloid cells.

PMID- 9538865
TI  - Entamoeba histolytica: solubilization and biochemical characterization of
      dolichol phosphate mannose synthase, an essential enzyme in glycoprotein
      biosynthesis.
AB  - Sequential treatment of trophozoite membranes with the nonionic detergents Brij
      35 and Igepal CA-630 released a soluble fraction that efficiently catalyzed the
      transfer of mannose from GDP-Man into a mannolipid that was identified as
      dolichol phosphate mannose (Dol-P-Man) by several criteria. The transfer reaction
      occurred only in the presence of exogenously added dolichol monophosphate (Dol
      P). Plots of enzyme velocity versus Dol-P and GDP-Man concentrations revealed
      sigmoidal and hyperbolic kinetics, respectively. Values of S0.5 for Dol-P and
      K(m) for GDP-Man were 15 micrograms/ml and 4.1 microM, respectively. The
      solubilized fraction failed to transfer the label into other products such as
      lipid-linked oligosaccharides and glycoproteins. The optimum pH was 7.5-8.0 in
      potassium phosphate or Tris/HCl buffers and the enzyme required either Mg2+ or
      Mn2+. The latter was more effective but in a narrower range of concentrations.
      The transferase was inhibited by a number of nucleotides the strongest being GMP,
      GDP, and GTP. When assayed in the reverse direction, however, the enzyme
      catalyzed the transfer of mannose from Dol-P-Man back into GDP-Man as a function
      of increasing concentrations of GDP. Mg2+ was a better activator of the reverse
      reaction than Mn2+, which reached up to 60% at 2 mM GDP. These results suggest
      that some of the enzyme catalytic properties may change depending on the
      direction of the transfer reaction.

PMID- 9538866
TI  - Anticoagulant activity in salivary glands of the insect vector Culicoides
      variipennis sonorensis by an inhibitor of factor Xa.
AB  - Blood feeding by the insect vector Culicoides variipennis sonorensis involves
      laceration of superficial host tissues, an injury that would be expected to
      trigger the coagulation cascade. Accordingly, the salivary glands of C.v.
      sonorensis were examined for the presence of an antihemostatic that prevents
      blood coagulation. Assays using salivary gland extracts showed a delay in the
      recalcification time of plasma devoid of platelets, indicating the presence of
      anticoagulant activity. Retardation in the formation of a fibrin clot was also
      observed after the addition of tissue factor to plasma that was preincubated with
      salivary gland extracts. Similarly, an inhibitory effect by salivary gland
      extracts was detected in assays that included factors of the intrinsic pathway.
      Inhibition of the catalytic activity of purified factor Xa toward its chromogenic
      substrate suggested that it was the target of the salivary anticoagulant of C.v.
      sonorensis. This was corroborated by the coincidence of anticoagulant and anti
      FXa activities obtained by reverse-phase HPLC. The depletion of anti-FXa activity
      from salivary glands during blood feeding suggests that the FXa inhibitor
      functions as anticoagulant. Molecular sieving HPLC yielded an apparent molecular
      mass of 28 kDa for the salivary FXa inhibitor of C.v. sonorensis. Preventing the
      formation of thrombin through the inhibition of FXa likely facilitates blood
      feeding by maintaining the pool of blood fluid at the feeding site. The salivary
      FXa inhibitor of C.v. sonorensis could impair the network of host-defense
      mechanisms in the skin microenvironment by avoiding blood coagulation at the site
      of feeding.

PMID- 9538867
TI  - Giardia intestinalis: characterization of a NADP-dependent glutamate
      dehydrogenase.
AB  - Glutamate dehydrogenase from Giardia intestinalis was purified 680-fold to
      electrophoretic homogeneity with a 42% recovery through a two-step procedure. The
      most effective step in the purification was the use of CM-Trisacryl that
      eliminated nearly 99% of the total proteins with 100% recovery. Matrix-assisted
      laser desorption ionization time-of-flight mass spectrometer was used to analyze
      the giardial glutamate dehydrogenase after deposition of the purified enzyme on a
      crystalline layer of 3,5-dimethoxy-4-hydroxy-trans-cinnamic acid. Use of this
      sample preparation technique allowed the first successful determination of the
      molecular mass of the enzyme (50,120 +/- 75). Since the molecular weight of the
      native enzyme was determined to be 270,000 by gel filtration, the enzyme appears
      to be a hexamer. The enzyme was specific for NADP(H) and functioned more
      favorably in the direction of glutamate formation than catabolism. The pH optimum
      was 7.5 for reductive amination of 2-oxoglutarate and 9.3 for oxidative
      deamination of glutamate. The apparent K(m) values were 0.28 mM for 2
      oxoglutarate and 17 microM for NADPH. An unusual biphasic saturation curve
      characterized the effect of ammonium ion on the activity with a plateau between
      40 and 55 mM.

PMID- 9538868
TI  - Ascaris suum: protein phosphotyrosine phosphatases in oocytes and developing
      stages.
AB  - Protein tyrosine phosphatases were analyzed in oocytes of Ascaris suum.
      Phosphatases dephosphorylating modified acidic lysozyme were present in high
      molecular-weight form (M(r) > 600,000) and as a 50- to 55-kDa protein in the
      soluble fraction. The low-molecular-weight form of the phosphatase cross-reacted
      with an antiserum raised against human T-cell protein tyrosine phosphatase and
      was not distinguishable from the 50- to 55-kDa protein tyrosine phosphatase
      previously described in the muscular layer of the adult worms (B. Schmid et al.
      1996, Molecular and Biochemical Parasitology 77, 183-192). The low-molecular
      weight form was also present on immunoblots of high-molecular-weight protein
      tyrosine phosphatase preparations after denaturing electrophoresis. The same or a
      similar form of the tyrosine phosphatase was also found in detergent extracts
      from the pelletal fraction. In addition, another tyrosine phosphatase of 180 kDa
      molecular mass that dephosphorylated myelin basic protein was also found in
      extracts from the soluble compartment as well as in detergent extracts from the
      pelletal fraction. It showed no cross-reactivity with antisera raised against
      soluble mammalian phosphatases and was resistant to inhibition by vanadate. While
      the activities of the myelin basic protein-dephosphorylating protein phosphatase
      remained fairly constant during early development of the oocytes, the activity of
      the enzyme dephosphorylating modified lysozyme in the pelletal fraction decreased
      to less than 10% of the initial activity between days 3 and 28 of incubation.
      Immunocytochemical studies of unfertilized and developing Ascaris eggs revealed
      association of protein tyrosine kinase and protein tyrosine phosphatase with the
      egg shell, in addition to their presence in the neighborhood of mitochondria. The
      amount of enzyme changed with the stage of development. In the larval stage (21
      days) protein tyrosine kinase had increased in the chitin layer of the shell and
      in the nuclei while the relative amount of tyrosine phosphatase decreased in
      accordance with the biochemical data.

PMID- 9538869
TI  - Dirofilaria immitis: heartworm infection converts histamine-induced constriction
      to endothelium-dependent relaxation in canine pulmonary artery.
AB  - Heartworm (Dirofilaria immitis) infection alters the behavior of vascular
      endothelial cells in vivo and in vitro, with the potential, therefore, to
      influence vascular function. Histamine, an autocoid implicated in the
      pathogenesis of parasitic and inflammatory diseases, is vasoactive, and causes
      endothelium-dependent relaxation in some vascular beds. Experiments were designed
      to determine if histamine is an endothelium-dependent vasodilator in in vitro
      rings of canine pulmonary artery from heartworm and control dogs; to elucidate
      the mechanisms involved in histamine vasoactivity; and to measure circulating
      levels of histamine. Dose-response relationships to histamine were done in rings
      of canine pulmonary artery from heartworm and control dogs, in the presence and
      absence of endothelial cells, the H1 receptor blocker tripelennamine, or the H2
      receptor blocker cimetidine. Histamine caused a dose-dependent constriction in
      control, that was not influenced by endothelial cell removal. However, histamine
      caused an endothelium-dependent relaxation in heartworm pulmonary artery that was
      converted to constriction by endothelial cell removal. In heartworm, histamine
      relaxation was mediated by H2 receptors, but did not appear to involve nitric
      oxide or cyclooxygenase products. While diseases cause depression of endothelium
      dependent relaxation, this is the first report of a disease that changes a
      constriction response to an endothelium-dependent relaxation.

PMID- 9538871
TI  - Trypanosoma brucei: identification and purification of a poly(A)-binding protein.

PMID- 9538870
TI  - Plasmodium berghei: in vivo efficacy of albendazole in different rodent models.

PMID- 9538872
TI  - CD44H localization in primary open-angle glaucoma.
AB  - PURPOSE: Primary open-angle glaucoma (POAG) is associated with a decreased
      content of hyaluronan in the trabecular meshwork and in the juxtacanalicular
      connective tissue. In this study, the authors examined selected regions of the
      anterior segment to localize and determine the content of CD44H, a transmembrane
      multifunctional glycoprotein and the principal receptor of hyaluronan. METHODS:
      Sections of ethanol-fixed anterior segments of six POAG and six normal postmortem
      eyes were analyzed by immunostaining with and without the nonionic detergent
      Triton X-100, using the CD44H monoclonal antibody, and the avidin/biotin complex.
      They were visualized by Vector VIP substrate and were quantitated by computer
      aided color image analysis. RESULTS: CD44H was expressed in all regions.
      Statistically significant decreased content of CD44H was observed in the POAG
      regions compared with normal regions--ciliary muscle (P < 0.001), ciliary stroma
      (P < 0.001), anterior iris (P < 0.05), iris root (P < 0.05), and trabecular
      meshwork (P < 0.05)--and in a subgroup of nonlaser POAG juxtacanalicular
      connective tissue (P < 0.05) and trabecular meshwork (P < 0.01). In sections
      treated with Triton X-100 a further increase in immunostaining was observed in
      normal eyes. As evidenced by scattergram plots of the ciliary body stroma region
      of the change in the optical density of CD44H between pretreatment with Triton X
      100 and without Triton X-100 (y axis) versus the optical density of CD44H without
      Triton X-100 (x axis), individual cases of POAG were separated from normals.
      CONCLUSIONS: These results indicate that CD44H may represent a marker of POAG and
      an etiologic factor in the POAG disease process.

PMID- 9538873
TI  - Ribozyme-targeted destruction of RNA associated with autosomal-dominant retinitis
      pigmentosa.
AB  - PURPOSE: To design ribozymes--catalytic RNA molecules--to cleave the P23H and
      S334Ter mutant mRNA selectively and to test them in vitro to determine their
      potential as therapeutic agents in the prevention of autosomal dominant retinitis
      pigmentosa. METHODS: Synthetic RNA targets were used in cleavage assays to
      determine the catalytic efficiencies of the ribozymes in vitro. Cleavage products
      were analyzed by denaturing polyacrylamide gel electrophoresis. Total retinal RNA
      was also used as a substrate, and opsin mRNA cleavage was assayed by reverse
      transcription-polymerase chain reaction. RESULTS: All three ribozymes cleaved the
      mutant target specifically. Substrate cleavage was seen in less than 5 mM
      magnesium and was detectable after 15 minutes of incubation. The most active
      ribozyme against the P23H target was the hammerhead (kcat:K(m) [Michaelis-Menton
      constant] ratio = 5 x 10(7) M/min), then the P23H hairpin ribozyme (kcat:K(m)
      ratio = 9 x 10(5) M/min) and the S334Ter hammerhead (kcat:K(m) ratio = 8 x 10(5)
      M/min). No cleavage activity was observed, when wild-type target sequences or
      inactive control ribozymes were used. The ribozymes bound and specifically
      digested the intact mutant opsin mRNA in the presence of all normal retinal RNA.
      CONCLUSIONS: Ribozymes can discriminate between the mutant and wild-type
      sequences of mRNA associated with autosomal dominant retinitis pigmentosa. The
      kinetics and specificity of ribozyme cleavage indicate that they should reduce
      the amount of aberrant rhodopsin in the rod cells and may have potential as
      therapeutic agents against genetic disease.

PMID- 9538874
TI  - Localization of HRG4, a photoreceptor protein homologous to Unc-119, in ribbon
      synapse.
AB  - PURPOSE: To characterize further HRG4, a novel photoreceptor protein recently
      identified by subtractive cDNA cloning, by sequence analysis and
      immunolocalization. METHODS: The rat homolog of HRG4, RRG4 was expressed and used
      to prepare an antibody. The antibody was used in Western blot analysis, and
      immunofluorescent localization at the light and electron microscopic levels of
      HRG4-RRG4 protein. The HRG4-RRG4 sequence was also analyzed for homologies.
      RESULTS: HRG4-RRG4 showed 57% homology with unc-119, a Caenorhabditis elegans
      neuroprotein causing defects in locomotion, feeding, and chemosensation when
      mutated. By Western blot analysis, the HRG4-RRG4 protein was demonstrable only in
      retina and was soluble in nature. Immunofluorescence microscopic study of human
      and rat retinas, using the HRG4-RRG4 antibody, and other rod and cone
      photoreceptor-specific antibodies showed that the HRG4-RRG4 protein is localized
      in the outer plexiform layer of the retina in the synaptic termini of rod and
      cone photoreceptors. Electron microscopic immunolocalization showed the protein
      in the cytoplasm and on the presynaptic membranes of the photoreceptor synapses.
      CONCLUSIONS: The homology to unc-119 and localization to the photoreceptor
      synapse are suggestive of a function for HRG4-RRG4 in photoreceptor
      neurotransmission. HRG4 is the first photoreceptor-enriched synaptic protein to
      be reported, suggesting that its function may be unique to the specialized ribbon
      synapses formed between photoreceptors and the horizontal and bipolar cells of
      the retina.

PMID- 9538875
TI  - Transforming growth factor-beta 1 promotes contraction of collagen gel by bovine
      corneal fibroblasts through differentiation of myofibroblasts.
AB  - PURPOSE: To determine whether the ability of transforming growth factor-beta (TGF
      beta) to influence the contractile activity of corneal fibroblasts depends on
      their differentiation into myofibroblasts. METHODS: Bovine corneal fibroblasts
      were cultured on collagen gel in MED 5 medium (F-12 nutrient mixture supplemented
      with 5% fetal bovine serum) with or without TGF-beta 1 (0.01-10 ng/ml). To
      evaluate the corneal fibroblast-derived contraction of collagen gel, the
      thickness of the gel was measured daily for 6 days. The total number of cells on
      the gel was counted with a Coulter counter. The detection of alpha-smooth muscle
      actin (alpha-SMA); a marker for myofibroblasts, on these cells was performed
      immunocytochemically by using a mouse monoclonal antibody against alpha-SMA. The
      number of myofibroblasts (alpha-SMA-positive cells) was determined. RESULTS: The
      control gels containing bovine corneal fibroblasts that were cultured with the
      MED 5 medium alone significantly contracted to 72.3 +/- 1.2% of their original
      thickness after 6 days. TGF-beta 1 increased the contraction of collagen gel
      mediated by bovine corneal fibroblasts in a dose-dependent manner. Approximately
      0.2% of the cells on the control gels cultured with MED 5 medium alone were alpha
      SMA positive. TGF-beta 1 significantly increased the expression of alpha-SMA in a
      dose-dependent manner. There was no significant correlation between the thickness
      of the collagen gel and the total number of cells. However, there was a
      significant negative correlation between the thickness of collagen gel and the
      number of myofibroblasts. CONCLUSIONS: TGF-beta 1 increased the contractile
      activity of bovine corneal fibroblasts and their ability to differentiate into
      myofibroblasts. Because contractile activity was correlated with differentiation,
      the influence of TGF-beta 1 on corneal fibroblast-induced collagen gel
      contraction may depend on the promotion of myofibroblast differentiation.

PMID- 9538876
TI  - Quantitative evaluation of irregular astigmatism by fourier series harmonic
      analysis of videokeratography data.
AB  - PURPOSE: To assess quantitatively corneal irregular astigmatism in association
      with best spectacle-corrected visual acuity. METHODS: Refractive powers on a mire
      ring measured with computerized videokeratography were decomposed, using the
      Fourier series harmonic analysis. Extracting spherical and regular astigmatic
      components, the remaining irregular astigmatic component was quantified on rings
      2 through 9. A weighted average was calculated by using the Stiles-Crawford
      effect on the basis of the radius of each ring of each eye and was used as an
      index of the irregular astigmatic component. Data analyses were carried out in
      108 eyes, including 53 normal eyes, 34 eyes with keratoconus, and 21 eyes that
      had undergone penetrating keratoplasty for keratoconus. Keratoconic eyes and eyes
      after keratoplasty were included in the study only if visual acuity, corrected
      with a hard contact lens, was 20/20 or better. Logarithm of best spectacle
      corrected visual acuity, age, type of disease, refractive astigmatism, irregular
      astigmatic component, surface regularity index, and surface asymmetry index were
      analyzed. RESULTS: In results of multiple regression analysis, the irregular
      astigmatic component was significantly correlated with best spectacle-corrected
      visual acuity (r = -0.744; adjusted R2 = 0.549; P < 0.001), whereas other
      explanatory variables showed no correlation with best spectacle-corrected visual
      acuity. CONCLUSIONS: This model of the irregular astigmatic component seems to be
      an efficient, quantitative means of describing corneal irregular astigmatism.

PMID- 9538877
TI  - Expression and distribution of adhesion molecule CD44 in healing corneal
      epithelia.
AB  - PURPOSE: To study isoform expression and cellular distribution of CD44, a cell
      surface glycoprotein thought to be an adhesion molecule in cell-cell and cell
      substratum interactions, during corneal epithelial wound healing. METHODS:
      Reverse transcription-polymerase chain reaction was performed to determine
      alternatively spliced rat CD44 isoforms. In situ hybridization was carried out on
      frozen sections of the rat corneas obtained at different time points after
      epithelial debridement. 35S-Labeled sense and antisense cRNA that recognizes rat
      CD44 standard form was used as a probe. Immunofluorescence was used to assess
      expression and localization of CD44 in the rat corneas during
      reepithelialization. RESULTS: Corneal epithelia contained several alternatively
      spliced CD44 variants. Four large CD44 variants with inserts V1 through V10, V2
      through V10, V3 through V10, and V4 through V10 were differentially expressed in
      migratory epithelia. The silver grains, indicating CD44 transcripts, started to
      increase in the epithelial cells surrounding the wound margin 3 hours after
      wounding and peaked at 18 hours in the basal epithelial cell layers, at which
      time the epithelia were actively migrating. As the cells began proliferation
      after wounding, the density of CD44 mRNA label declined but was still
      significantly higher than that in control specimens. The label returned to basal
      level as epithelial cells reverted to their normal phenotype. The location of
      CD44 on cell surfaces during corneal reepithelialization was consistent with the
      pattern of mRNA production. In the corneas at 18 hours after wounding, CD44
      immunoreactivity was elevated in the entire epithelium, from the leading edge to
      the limbal-corneal border. As happened for the mRNA, the cell surface CD44
      declined as cells differentiated to reestablish the multilayered epithelium.
      CONCLUSIONS: The expression of CD44 correlates with corneal reepithelialization,
      suggesting that CD44 may be involved in cell-cell interactions that provide
      adhesive strength for the much-stressed epithelial sheet and in the cell
      substratum interactions that mediate cell migration during reepithelialization.

PMID- 9538878
TI  - Implicit time topography of multifocal electroretinograms.
AB  - PURPOSE: To describe the implicit time topography of multifocal
      electroretinograms in normal subjects and to examine the change in this
      topography in patients affected by retinitis pigmentosa. METHODS: Thirty normal
      subjects and 38 patients with retinitis pigmentosa were examined with the Visual
      Evoked Response Imaging System using 61 hexagonal elements within a visual field
      of 30 degrees radius. The peak implicit times of the 61 first-order kernels
      (which are analogues of the photopic electroretinogram [ERG]) were measured to
      determine their distribution across the retina. RESULTS: Implicit times had a low
      interindividual variability in the normal group. High implicit times were found
      at the blind spot, the upper and lower borders of the stimulated field, and the
      macula. Low values were present in the area encircling the macula and were most
      prominent in the temporal retina. In the group with retinitis pigmentosa,
      implicit times were unchanged in the central region but were prolonged in the
      peripheral regions. CONCLUSIONS: The spatial distribution of multifocal ERG
      implicit times in a normal population follows a specific topographical pattern
      across the retina. This pattern has to be taken into account when interpreting
      results in patients. Deviations in retinitis pigmentosa were found, and they show
      the potential for diagnostic use.

PMID- 9538879
TI  - Anomalies of motion perception in infantile esotropia.
AB  - PURPOSE: To quantify motion sensitivity in patients with infantile esotropia who,
      as a subgroup, have been previously reported to have abnormal oculomotor control.
      In addition, to probe abnormal binocular development as a factor underlying
      abnormal motion perception in infantile esotropia (IE), motion sensitivity was
      compared among participants with and without stereopsis. METHODS: Monocular
      sensitivity to leftward and rightward motion was assessed across the horizontal
      meridian, using partially coherent random dot kinematograms. Participants
      included 11 observers with IE, 5 observers with acquired esotropia, and 11
      observers with normal eye alignment. RESULTS: Participants with IE showed no
      deficits in motion sensitivity to any visual field locations when motion
      thresholds were collapsed across direction. However, they showed an abnormal
      variation in directional anisotropy. Although sensitivity to centripetal motion
      was superior in both hemifields of control participants and in the temporal
      hemifields of participants with IE, a centrifugal bias was revealed in the nasal
      hemifields of IE. Stereoblind observers with acquired esotropia showed a normal
      centripetal directional anisotropy, whereas binocular observers with acquired
      esotropia showed directional anisotropy similar to that in the IE group.
      CONCLUSIONS: Motion perception, like oculomotor function in IE, is characterized
      by a variation of directional anisotropy for stimuli presented to the nasal
      hemifields. This finding supports the hypothesis that abnormal oculomotor control
      and motion perception in IE reflect a common disruption of the visual system. A
      similar variation of directional sensitivity in patients with acquired esotropia
      with normal stereopsis suggests that the interruption of binocularity is not the
      underlying cause of abnormal motion perception in IE.

PMID- 9538880
TI  - Effects of topical nipradilol, a beta-blocking agent with alpha-blocking and
      nitroglycerin-like activities, on aqueous humor dynamics and fundus circulation.
AB  - PURPOSE: To study the effects of nipradilol, a nonselective beta-blocker with
      alpha 1-blocking activity and nitroglycerin-like activity, on aqueous humor
      dynamics and optic nerve head (ONH) circulation in albino rabbits. METHODS:
      Experiments were carried out during the dark phase, in conscious rabbits
      conditioned to a schedule of alternating 12-hour periods of light and dark. The
      blood-aqueous barrier permeability and the aqueous flow rate were determined
      fluorophotometrically. The effect on outflow to general blood circulation and
      uveoscleral outflow were determined by using the fluorophotometric Diamox
      technique, and the effect on the uveoscleral outflow was further assessed by
      using the anterior chamber perfusion method. The ONH circulation was estimated by
      using the laser speckle method. RESULTS: Unilateral topical administration of
      0.25% nipradilol solution lowered intraocular pressure (IOP) with relatively weak
      contralateral effects in a dose-dependent manner with a maximum reduction of 6 mm
      Hg and an effect duration of 6 hours. Twice-daily instillation for 14 days showed
      no attenuation of the effects. Single instillation of 0.25% nipradilol showed no
      significant effect on blood-aqueous barrier permeability and decreased aqueous
      flow rate in the treated eye (17%; P < 0.01) and in the contralateral eye (9%, P
      < 0.05). Nipradilol produced no significant effect on outflow facility to general
      blood circulation, whereas it substantially increased uveoscleral outflow. Twice
      daily 0.25% nipradilol instillation increased ONH tissue blood velocity by 13% (P
      < 0.01), which was probably attributable to locally penetrating drug.
      CONCLUSIONS: Because of its ability to lower IOP and to increase uveoscleral
      outflow and optic nerve head circulation in rabbits, further studies are
      warranted to determine whether nipradilol has potential as an antiglaucoma agent
      in humans.

PMID- 9538881
TI  - Immunologic phenotype of hosts orally immunized with corneal alloantigens.
AB  - PURPOSE: To evaluate the immunologic phenotype of hosts tolerized by oral
      administration of corneal alloantigens. METHODS: CB6F1 mice were tolerized by
      oral administration of allogeneic C3H/Hej corneal epithelial and endothelial
      cells before receiving heterotopic C3H/Hej corneal allografts. C3H-specific
      cytotoxic T-lymphocyte (CTL), delayed-type hypersensitivity (DTH), and mixed
      lymphocyte responses were evaluated in orally tolerized and control mice.
      Cytokine profiles of Peyer's patch cells from orally tolerized mice were
      determined by enzyme-linked immunosorbent assay and mink lung cell culture
      bioassay. RESULTS: Oral administration of corneal cells produced a profound
      inhibition of allospecific CTL, DTH, and mixed-lymphocyte responses. Conjugation
      with the B subunit of cholera toxin markedly increased the tolerizing activity of
      corneal endothelial cells, so that a single dose of cholera toxin-conjugated
      corneal cells inhibited alloimmune responses to the same degree as 10 doses of
      corneal cells unconjugated with cholera toxin. Peyer's patch cells from orally
      tolerized mice produced reduced quantities of interferon-gamma and interleukin-2
      but produced increased amounts of transforming growth factor-beta and interleukin
      10 compared with concentrations in normal control animals. CONCLUSIONS: Oral
      administration of cholera toxin-conjugated corneal cells produces a dose
      dependent inhibition of allospecific CTL, DTH, and mixed-lymphocyte responses.
      Orally induced inhibition of cell-mediated immune responses to corneal
      alloantigens is correlated with a sharp increase in the secretion of transforming
      growth factor-beta and interleukin-10 and a concomitant suppression of
      interleukin-2 and interferon-gamma. The well-recognized immunosuppressive
      characteristics of transforming growth factor-beta and interleukin-10 are
      suggestive that orally induced tolerance to corneal alloantigens is mediated by
      these cytokines.

PMID- 9538882
TI  - T cell traffic and the inflammatory response in experimental autoimmune
      uveoretinitis.
AB  - PURPOSE: To quantify S-antigen-specific (S-Ag) T cells in the retina after
      adoptive transfer, and to evaluate their role in the initiation and progress of
      destructive ocular inflammation in experimental autoimmune uveoretinitis (EAU).
      METHODS: Lewis rats were administered 10 x 10(6) S-Ag-specific T cells from the
      SP35 cell line or 10 x 10(6) concanavalin A-stimulated syngeneic spleen cell
      lymphoblasts labeled with lipophilic PKH26 fluorescent dye immediately before
      intravenous inoculation. Labeled cells in each retina were counted at various
      times from 4 to 120 hours after cell transfer by fluorescence microscopic
      analysis of each dissociated retina. Recipient eyes were examined within the same
      period by light and confocal microscope. RESULTS: SP35 T cells showed a biphasic
      distribution in the retina. The first peak of 160 cells/retina was noted at 24
      hours. A steady decline of labeled cells at 48 and 72 hours was followed by a
      rapid increase at 96 and 120 hours. Concanavalin A-stimulated, control-labeled
      cell populations showed an identical peak at 24 hours but a persistent decline
      thereafter; only two or three T cells were present in each retina at 120 hours.
      Concurrent inoculation of SP35 cells and nonspecific T cell blasts did not
      produce more SP35 cells than control cells in the retina at any time. Microscopic
      analysis showed mononuclear cell infiltration of the iris, ciliary body, and
      aqueous humor at 48 hours, which intensified rapidly and persisted through 120
      hours. Retinal inflammation did not begin until 80 hours. Mononuclear cell
      adherence to vascular endothelium and perivascular macrophage infiltration of the
      innermost layers progressed to edema, and profound destructive inflammation and
      loss of retinal stratification were observed at 120 hours. CONCLUSIONS: There is
      no evidence of a blood-ocular or blood-retinal barrier to activated T cell
      blasts. Autologous S-Ag does not provoke a more rapid entry of specific T cells
      at that site. The data confirm that anterior segment inflammation precedes
      retinal inflammation, even though S-Ag-specific T cells were present in the
      retina within a few hours after cell transfer. Because S-Ag is clearly present in
      the retina, delay in antigen presentation at that site may account for the
      temporal difference between retinal and anterior segment inflammation.

PMID- 9538883
TI  - Na,K-ATPase polypeptide upregulation responses in lens epithelium.
AB  - PURPOSE: In a previous study, an increase in Na,K-ATPase alpha 2 expression was
      detected in the epithelium of porcine lenses exposed to amphotericin B, an
      ionophore that also increases lens sodium and stimulates active sodium transport.
      The purpose of the present study was to determine whether an increase of Na,K
      ATPase alpha 2 synthesis is a response to an episode of rapid Na-K transport or
      whether the increase in lens sodium alone can initiate the response. METHODS:
      Western blot analyses were conducted to probe for Na,K-ATPase alpha polypeptides
      in membrane material isolated from porcine lens epithelium. Ouabain-sensitive
      adenosine triphosphate hydrolysis was used as an index of Na,K-ATPase activity,
      and lens ion content was determined by atomic absorption spectrophotometry. 86
      Rubidium (86Rb) uptake was measured as an indicator for active potassium
      transport. RESULTS: 86Rb uptake was markedly diminished in lenses exposed to
      dihydro-ouabain (DHO), signifying inhibition of active sodium-potassium
      transport. Consistent with this, the sodium content of DHO-treated lenses
      increased. By western blot analysis, a marked increase of Na,K-ATPase alpha 2
      polypeptide could be detected in the epithelium of DHO-treated lenses. To rule
      out the possibility that apparent stimulation of Na,K-ATPase alpha 2 synthesis
      stemmed from binding of DHO to Na,K-ATPase sites, experiments were conducted to
      confirm an increase of Na,K-ATPase alpha 2 polypeptide in the epithelium of
      lenses exposed to low-potassium medium to inhibit active sodium-potassium
      transport. Consistent with the apparent increase of Na,K-ATPase polypeptide, Na,K
      ATPase activity was detectably increased in epithelial material isolated from
      lenses pretreated with DHO or low-potassium medium. CONCLUSIONS: An increase in
      Na,K-ATPase alpha 2 polypeptide can occur in the epithelium of lenses subjected
      to an episode of sodium pump inhibition. This suggests the response could be
      triggered by an increase in cell sodium and does not necessarily require a period
      of stimulated active sodium-potassium transport.

PMID- 9538884
TI  - Alterations of retinal microcirculation in response to scatter photocoagulation.
AB  - PURPOSE: To perform acridine orange digital fluorography on rats after scatter
      photocoagulation to investigate alterations of retinal microcirculation at the
      capillary level, the authors used leukocyte dynamics as a parameter. METHODS:
      Twenty-five pigmented rats (Long-Evans) were studied. Argon laser
      photocoagulation, extending 6 disc diameters from the optic disc, was delivered
      to one half of the retina, and the other half was untreated. The total number of
      burns was 200 +/- 10. Leukocyte hemodynamics in retinal microcirculation were
      evaluated 4, 7, 14, and 28 days after photocoagulation by acridine orange digital
      fluorography. The fundus image was obtained by using an argon laser in a scanning
      laser ophthalmoscope and was recorded on magnetic tapes at a video rate. The
      images were analyzed by a personal computer-based image analysis system. RESULTS:
      Leukocyte velocities in the retinal capillaries were significantly decreased
      immediately after photocoagulation. In the laser-treated area, mean capillary
      leukocyte velocities were 0.73, 0.92, 1, and 1.3 mm/second on days 4, 7, 14, and
      28, respectively (velocity in normal control animals 1.4 mm/second). In addition,
      leukocyte hemodynamics were compromised in the untreated retina: Mean capillary
      leukocyte velocities were 0.88, 1.1, 1.2, and 1.3 mm/second on days 4, 7, 14, and
      28, respectively. Twenty-eight days after photocoagulation, the velocities
      recovered to normal values in the treated and the untreated areas of the retina.
      CONCLUSIONS: Retinal capillary hemodynamics were impaired after scatter
      photocoagulation, and the hemodynamics in the untreated retina were also
      affected. Photocoagulation to the retina may influence capillary hemodynamics by
      diffusible chemical substances and by direct tissue injury.

PMID- 9538886
TI  - Immunocytochemical localization of glutamate in normal and detached cat retina.
AB  - PURPOSE: Glutamate immunoreactivity in the mammalian retina has generally been
      observed using immersion fixation. The authors investigated glutamate
      immunoreactivity in the detached cat retina and reevaluated this activity in the
      normal retina using rapid fixation by perfusion. METHODS: Unilateral retinal
      detachment was produced in cats by injecting 0.25% sodium hyaluronate into the
      subretinal space using a glass micropipet. The eyes were fixed by perfusion with
      a mixture of 1% glutaraldehyde and 4% formaldehyde 10 minutes and 60 minutes
      after detachment, and then they were examined by conventional light and electron
      microscopic immunocytochemistry. RESULTS: In contrast to previous reports based
      on immersion fixation, the inner segment was not glutamate immunopositive in the
      normal retina. The inner segment showed intense glutamate immunoreactivity 10
      minutes and 60 minutes after retinal detachment. CONCLUSIONS: Glutamate
      immunoreactivity in photoreceptor inner segments may be a postmortem change
      induced by strong ischemia. Perfusion fixation is of critical importance when
      studying the immunocytochemical distribution of glutamate in the retina.

PMID- 9538885
TI  - Preconditioning provides complete protection against retinal ischemic injury in
      rats.
AB  - PURPOSE: The objectives of this study were to examine whether preconditioning can
      decrease ischemic damage to the retina, by electroretinographic assessment of
      visual function and by histologic examination of retinal structure; to
      investigate the time course of the effectiveness of preconditioning; and to
      determine whether protein synthesis is involved. METHODS: Retinal ischemia was
      produced for 60 minutes in anesthetized Sprague-Dawley rats. Recovery after
      ischemia was measured by electroretinography for a maximum period of 7 days.
      Retinal sections that were sliced 1 micron thick were examined 7 days after
      ischemia. Retinal ischemia for 5 minutes constituted the preconditioning
      stimulus. To assess the time course of preconditioning, animals first underwent
      preconditioning and then 60 minutes of ischemia 1, 24, 72, or 168 hours later; or
      they underwent a 5-minute sham experiment and 60 minutes of ischemia 24 hours
      later. An additional group of rats received 0.4 mg/kg cycloheximide, the protein
      synthesis inhibitor, intraperitoneally before preconditioning and underwent 60
      minutes of ischemia 24 hours later. RESULTS: In contrast to the nonpreconditioned
      rats, preconditioned rats had complete recovery of the a- and b-waves compared
      with preischemic baseline amplitudes, and ischemia-induced histologic damage was
      completely prevented when preconditioning was performed 24 or 72 hours (but not
      168 hours) before ischemia. Separation of preconditioning and 60 minutes of
      ischemia by 1 hour caused an even greater impairment of functional retinal
      recovery compared with that seen in sham-preconditioned rats. Severe histologic
      damage was also noted. Block of protein synthesis by cycloheximide completely
      attenuated the protective effect of preconditioning. CONCLUSIONS: Preconditioning
      induces profound retinal tolerance to ischemia in vivo. The absence of a
      protective effect of preconditioning when there was a 1-hour or a 168-hour
      separation between the preconditioning stimulus and ischemia and the inhibition
      of preconditioning by cycloheximide support the hypothesis that a transient
      change in protein expression is necessary to provide this protection.

PMID- 9538887
TI  - In vivo evaluation of leukocyte dynamics in retinal ischemia reperfusion injury.
AB  - PURPOSE: To evaluate quantitatively leukocyte dynamics in vivo in the rat retinal
      microcirculation during ischemia reperfusion injury with the use of acridine
      orange digital fluorography. METHODS: Retinal ischemia was induced in
      anesthetized pigmented rats by a temporary ligation of the optic nerve. After 60
      minutes of ischemia, leukocyte behavior in the retinal microcirculation was
      evaluated, with acridine orange digital fluorography--consisting of a scanning
      laser ophthalmoscope and the fluorescent nuclear dye, acridine orange--during
      reperfusion at 1, 2, 4, 6, 12, 24, 48, 96, and 168 hours. The obtained images
      were recorded on videotape and analyzed with a computer-assisted image analysis
      system. RESULTS: Rolling leukocytes along the major retinal veins were observed
      in treated rats during the reperfusion period; no rolling leukocytes were
      observed in the control rats. The number of rolling leukocytes gradually
      increased and peaked at 102 +/- 40 cells/minute 12 hours after reperfusion; few
      rolling leukocytes were observed at 96 hours. The velocity of rolling leukocytes
      at 12 hours (19.1 +/- 3.5 microns/second; P < 0.05) was significantly lower than
      that at the other three times. No rolling leukocytes were observed along the
      arterial walls throughout the experiments. The number of accumulated leukocytes
      increased as time elapsed, peaked at 931 +/- 187 cells/mm2 24 hours after
      reperfusion, and decreased thereafter. CONCLUSIONS: Leukocyte dynamics in the
      retinal microcirculation can be quantitatively evaluated during ischemia
      reperfusion injury.

PMID- 9538888
TI  - Upregulation of transforming growth factor-beta after panretinal
      photocoagulation.
AB  - PURPOSE: To determine whether upregulation of transforming growth factor-beta
      (TGF-beta) gene expression occurs after panretinal photocoagulation (PRP). To
      quantitate two TGF-beta isoforms in the aqueous and vitreous humors and to
      localize TGF-beta 2-like immunoreactivities (TGF-beta 2-LI) and TGF-beta 2 mRNA
      in the retina after PRP. METHODS: PRP was performed on Brown Norway rats by using
      an argon-green laser. Sensory retina, aqueous and vitreous humors were collected
      from the rats on days 1, 3, and 7 after PRP, and semiquantitative polymerase
      chain reaction analyses were carried out. TGF-beta 2 in the aqueous and vitreous
      humors was quantitated by enzyme-linked immunosorbent assay. Localization of TGF
      beta 2-LI was demonstrated by immunohistochemistry, and that of TGF-beta 2 mRNA
      by in situ reverse transcription-polymerase chain reaction (RT-PCR). RESULTS:
      Gene expression of both TGF-beta 1 and -beta 2 was upregulated by PRP. Expression
      of TGF-beta 2 was greater than that of beta 1 (12.8-fold increase versus 3.24
      fold increase, respectively, compared with control level on day 3). TGF-beta 2
      concentration was increased in the vitreous humor (4.37-fold increase, P < 0.01)
      but not in the aqueous humor (the same level compared with control) on day 1. TGF
      beta 2-LI and TGF-beta 2 mRNA were detected in cells of the outer retinal layer
      and in retinal pigment epithelial cells adjacent to the laser burns. CONCLUSIONS:
      PRP upregulates expression of TGF-beta 2 in the retina, and increased TGF-beta 2
      concentrations are found in the retina and the vitreous humor. Retinal pigment
      epithelial cells and sensory retina around the laser burn appear to play a major
      role in the upregulation.

PMID- 9538889
TI  - Rhodopsin transgenic pigs as a model for human retinitis pigmentosa.
AB  - PURPOSE: To further characterize the retinas of Pro3471Leu rhodopsin transgenic
      pigs, a model for human retinitis pigmentosa. METHODS: Retinas from normal and
      transgenic pigs, newborn to 20 months old, were processed for light and electron
      microscopic immunocytochemical examination. RESULTS: At birth, rod numbers were
      normal in the transgenic retinas, but their outer segments were short and
      disorganized and their inner segments contained stacks of rhodopsin-positive
      membranes. The newborn rod synapses lacked synaptic vesicles and ribbons and had
      numerous rhodopsin-positive, filopodia-like processes that extended past the cone
      synapses into the outer plexiform layer. Rod cell death was apparent by 2 weeks
      and was pronounced in the mid periphery and central regions by 6 weeks. Far
      peripheral rods were initially better preserved, but by 9 months virtually all
      rods had degenerated. Cones degenerated more slowly than rods, but by 4 weeks the
      cone synapses were shrunken and some mid peripheral cones had lost their
      immunoreactivity for phosphodiesterase-gamma, arrestin, and recoverin. From 9
      months to 20 months, the cone outer segments shortened progressively, and more
      cones lost immunoreactivity for these proteins. CONCLUSIONS: The rhodopsin
      transgenic pig retina shares many cytologic features with human retinas with
      retinitis pigmentosa and provides an opportunity to examine the earliest stages
      in photoreceptor degeneration, about which little is known in humans. The finding
      of abnormal rhodopsin localization in newborn rods is consistent with misrouting
      of mutant rhodopsin as an early process leading to rod cell death. Novel changes
      in the photoreceptor synapses may correlate with early electrophysiological
      abnormalities in these retinas.

PMID- 9538890
TI  - Prevention of ornithine cytotoxicity by proline in human retinal pigment
      epithelial cells.
AB  - PURPOSE: To investigate the relationship between ornithine-delta-aminotransferase
      (OAT) deficiency and ornithine accumulation and the specific degeneration of
      retinal pigment epithelial (RPE) cells in gyrate atrophy. METHODS: Human RPE
      cells, human hepatoma cells, and human fibroblast cells were treated with 5
      fluoromethylornithine (5-FMOrn), a specific irreversible inhibitor of OAT.
      Ornithine cytotoxicity was determined by using a [3H]thymidine incorporation
      assay and immunohistochemical staining for cytokeratin. The effects of various
      metabolites of ornithine and arginine, such as creatine, creatine phosphate, I
      delta 1-pyrroline-5-carboxylic acid (L-P5C), and proline, which may be deficient
      in gyrate atrophy on RPE cell damage by ornithine, were determined by the same
      procedures. RESULTS: When the human RPE cells, HepG2 hepatoma cells, and WI-38
      fibroblast cells were treated with 0.5 mM 5-FMOrn for 30 minutes, which
      inactivated OAT, ornithine exhibited severe time- and dose-dependent inhibition
      of DNA synthesis in the human RPE cells but not in the HepG2 hepatoma cells or WI
      38 fibroblast cells. The inhibition of DNA synthesis was accompanied by drastic
      changes in morphologic appearance, disorganization of the cytoskeleton, and cell
      death. Ornithine or 5-FMOrn alone did not exhibit such cytotoxicity to the RPE
      cells. Proline prevented the cytotoxicity of ornithine. CONCLUSIONS: These
      findings suggest that an elevated level of ornithine combined with an increased
      sensitivity to ornithine as a result of OAT deficiency may be crucial to the
      specific RPE degeneration in gyrate atrophy. They suggest also that abnormalities
      of proline metabolism may be involved in the progress of gyrate atrophy.

PMID- 9538891
TI  - Missense mutation at the C terminus of the PAX6 gene in ocular anterior segment
      anomalies.
AB  - PURPOSE: To report a rare case of ocular anterior segment anomalies including
      uveal ectropion of the iris, invasion of the conjunctival epithelia into the
      cornea, and posterior embryotoxon with a missense mutation of the PAX6 gene.
      METHODS: The authors performed polymerase chain reaction-single-strand
      conformation polymorphism analysis and sequencing of the PAX6 gene using genomic
      DNA of family members and more than 100 control subjects. RESULTS: The A to G
      transition at nucleotide 1682 in exon 13 in the patient was identified in an
      allele that resulted in a Gln to Arg substitution (Q422R) at the C terminus of
      the protein. The mutation was not found in the parents, a sibling, or control
      subjects. CONCLUSIONS: The mutation indicates that the proline-serine-threonine
      rich domain at the C terminus of the PAX6 protein plays a role in ocular anterior
      segment morphogenesis.

PMID- 9538892
TI  - Noninvasive assessment of the hydration gradient across the cornea using confocal
      Raman spectroscopy.
AB  - PURPOSE: The feasibility of Raman spectroscopy for the noninvasive assessment of
      axial corneal hydration was investigated. METHODS: A scanning confocal Raman
      spectroscopy system, with an axial resolution of 50 microns, was used to assess
      noninvasively the water (OH-bond) to protein (CH-bond) ratio as a measure of the
      hydration in collagen-based phantom media and rabbit corneas. RESULTS: Raman
      spectra with high signal-to-noise ratios were obtained under in vitro and in vivo
      conditions within a range of corneal hydration (H = 0.0-8.3 mg water/mg dry wt).
      The Raman intensity ratio OH/CH showed a strong correlation with the hydration of
      the phantom medium (R2 > 0.99) and the rabbit corneas (R2 > 0.95). A degree of
      reproducibility was seen in measurements performed at a specific depth within the
      cornea (SD = 1.2%-2.7%). Quantitatively, the spatially resolved corneal water
      content, as assessed with our method, showed an increasing gradient from the
      anterior to the posterior region, with a difference of approximately 0.9.
      Significant qualitative differences in the axial hydration gradient were observed
      between the in vitro and in vivo situation, caused by the presence of an intact
      tear-film in vivo. Characterization of the axial corneal hydration using Raman
      spectroscopy provided a reliable estimation of total corneal hydration compared
      with conventional measurements using pachymetry and lyophilization. CONCLUSIONS:
      The proposed noninvasive confocal Raman spectroscopic technique has the potential
      to assess the axial corneal water gradient with a degree of sensitivity and
      reproducibility.

PMID- 9538893
TI  - Effects of mycophenolate mofetil on nasal mucosal tolerance induction.
AB  - PURPOSE: The authors investigated mucosal tolerance therapy as a treatment for
      autoimmune conditions, including uveitis. Although nasal antigen administration
      was unable to suppress the disease when given to primed animals, previous studies
      of experimental autoimmune uveoretinitis (EAU) have shown that nasal antigen
      administration can maintain disease suppression when combined with oral
      cyclosporin A. This study aimed to determine whether mucosal tolerance can be
      induced when EAU is suppressed with mycophenolate Mofetil (MM) and whether
      tolerance can be maintained when immunosuppression with MM is stopped. METHODS:
      Lewis rats were immunized with retinal extract, and then they received either
      oral MM 7 to 20 days after immunization or retinal extract intranasally in
      combination with oral MM on days 7 to 20. Thereafter, weekly nasal administration
      of the antigen was given until the termination of the experiment at day 38. One
      group of control animals received the drug vehicle orally and phosphate-buffered
      saline intranasally. Clinical and histologic changes were assessed along with
      changes in immune status including delayed-type hypersensitivity, antibody
      responses to retinal antigens, and flow cytometric phenotyping of infiltrating
      ocular leukocytes. RESULTS: EAU was delayed, but not prevented, by a short-term
      course of MM (7-20 days after immunization). Tolerance to the retinal extract
      could not be induced during MM treatment by nasal retinal extract administration.
      Despite the delay in onset of EAU in MM and in MM- and nasal antigen-treated
      animals, profound target organ damage occurred as seen in untreated controls with
      EAU. However, fluoroscein-activated cell sorter analysis of retinal leukocytic
      infiltrate indicated that there was a reduced macrophage recruitment at all time
      points, whereas lymphocyte infiltration was reduced in proportion to the overall
      reduction in leukocyte infiltration during therapy. CONCLUSIONS: Nasal retinal
      antigen administration does not induce tolerance or maintain disease suppression
      when combined with MM therapy during the effector stage of the (auto)immune
      response. MM therapy delays disease onset, but target organ damage occurs when
      therapy is stopped, despite a marked inhibition of macrophagemonocyte
      infiltration into the chorioretina.

PMID- 9538894
TI  - Abnormal panretinal response pattern to carbogen inhalation in experimental
      retinopathy of prematurity.
AB  - PURPOSE: Present technologies are not able to determine which retinas are at risk
      for the development of neovascularization in retinopathy of prematurity (ROP). In
      this study, the authors evaluated whether a novel magnetic resonance imaging
      (MRI) method could be used to identify differences between control retinas and
      those that will develop neovascularization in the newborn rat model of
      retinopathy of prematurity (ROP). METHODS: MRI and a 2-minute carbogen (95% O2/5%
      CO2) inhalation challenge (see ref. 11) were used to measure noninvasively the
      change in the posterior vitreous oxygen tension in specific locations across the
      full extent of the retina in day-12 rats raised in either room air (control, n =
      7) or variable oxygen conditions (experimental ROP, n = 7). The experimental ROP
      animals were examined 2 days before the onset of neovascularization. RESULTS: In
      the ROP group, the response to carbogen was lower (P < 0.05) at every distance
      from the optic nerve than in the control group. Within the ROP group, the
      vascular midperipheral retinal reaction to carbogen, 1 to 2 mm from the optic
      nerve, was as low as that from the avascular periphery, 2 to 3 mm from the optic
      nerve. Although the vascular central retinal response to carbogen, 0 to 1 mm from
      the optic nerve, was greater than either the vascular midperipheral retina or the
      avascular periphery in the ROP group, theoretically this difference could be
      caused by oxygen diffusing from the hyaloidal circulation. CONCLUSIONS: Carbogen
      challenge MRI seems to be a useful tool for assessing the risk of retinal
      neovascularization in the newborn rat ROP model. This MRI method has potential
      clinical applicability, for example, because effective laser therapy with retinal
      sparing may be possible if focal photocoagulation, guided by an MRI map, is
      performed.

PMID- 9538895
TI  - Light-induced cell death of retinal photoreceptors in the absence of p53.
AB  - PURPOSE: Cell death by apoptosis is essential for normal development and tissue
      homeostasis, and it is involved also in a variety of pathologic processes.
      Apoptosis is the final common pathway of photoreceptor cell death in retinal
      dystrophies and degeneration. So far, little is known about genes regulating
      apoptosis in the retina. The tumor-suppressor gene product p53 is a potent
      regulator of apoptosis in numerous systems. However, p53-independent apoptotic
      pathways also have been described. In this study the authors investigated the
      role of p53 in the light-induced apoptosis of retinal photoreceptors using mice
      lacking p53. METHODS: Free-moving p53-/- and p53+/+ mice were dark adapted and
      were exposed to 8,500 or 15,000 lux of diffuse, cool, white fluorescent light for
      2 hours. Animals were killed before and immediately after light exposure or at 12
      hours in darkness after light exposure. Eyes were enucleated and processed for
      light and electron microscopy and histochemistry (TdT-dUTP terminal nick-end
      labeling method). Isolated retinas were subjected to the extraction of total
      retinal DNA. Electroretinogram (ERG) recordings were performed at all time
      points. RESULTS: Morphologic, biochemical, histochemical, and ERG analysis showed
      that the retinas of untreated p53-/- mice and wild-type control mice were
      structurally and functionally indistinguishable. After exposure to diffuse white
      fluorescent light, light-induced photoreceptor cell death was analyzed and was
      found to be the same in both groups of mice. CONCLUSIONS: These data suggest that
      light-induced apoptosis of photoreceptors is independent of functional p53.

PMID- 9538896
TI  - Selective release of nitric oxide from retinal amacrine and bipolar cells.
AB  - PURPOSE: To investigate the cellular origin of nitric oxide released from the
      rabbit retina in response to physiological stimulation with light. METHODS: The
      release of nitric oxide from the retina was measured in rabbits anesthetized with
      urethane. An eye-cup was prepared and was filled with Krebs-Ringer bicarbonate.
      After washing for 45 minutes, 0.5 ml medium was placed in the eyecup. The medium
      was replaced every 10 minutes, and nitric oxide in the resultant samples was
      measured using nitrate reductase and a nitric oxide meter. RESULTS: In the
      unstimulated dark-adapted retina there was a spontaneous resting release of
      nitric oxide (1.20 nmol/min). When the retina was stimulated for 10 minutes with
      flickering light there was an increase in nitric oxide release to almost double
      the resting release. Stimulation of the retina for 10 minutes with continuous
      light produced a similar increase in nitric oxide release. The exposure of the
      retina to L-amino-4-phosphonobutyrate (APB), which specifically blocks
      transmission between the photoreceptors and the depolarizing bipolar cells,
      abolished the evoked release of nitric oxide caused by flickering light and
      continuous light. In contrast, the nonselective excitatory amino acid antagonist
      cis-2,3-piperidinedicarboxylic acid (PDA) had no effect on the flicker-evoked
      release of nitric oxide, but it more than halved the release caused by continuous
      light. A similar differential effect on release was found with glycine, which
      abolished the nitric oxide release evoked with continuous light but did not
      affect the flicker-evoked release. The inhibitory effect of glycine was blocked
      by strychnine. CONCLUSIONS: Nitric oxide was released in the retina by flickering
      light and by continuous light, but the two types of stimulation cause nitric
      oxide release from different cells. Because in the rabbit retina nitric oxide
      synthase occurs mainly in a subpopulation of amacrine cells and a few bipolar
      cells, our pharmacologic results suggest that continuous light causes nitric
      oxide release from amacrine cells, whereas flickering light evokes nitric oxide
      release from bipolar cells.

PMID- 9538897
TI  - Fine structure of lymphatics in the avian choroid.

PMID- 9538898
TI  - Protection of hippocampal neurons from ischemia-induced delayed neuronal death by
      hepatocyte growth factor: a novel neurotrophic factor.
AB  - Hepatocyte growth factor (HGF), a natural ligand for the c-met protooncogene
      product, exhibits mitogenic, motogenic, and morphogenic activities for
      regeneration of the liver, kidney, and lung. Recently, HGF was clearly shown to
      enhance neurite outgrowth in vitro. To determine whether HGF has a
      neuroprotective action against the death of neurons in vivo, we studied the
      effect of HGF on delayed neuronal death in the hippocampus after 5-minute
      transient forebrain ischemia in Mongolian gerbils. Continuous postischemic
      intrastriatal administration of human recombinant HGF (10 or 30 micrograms) for 7
      days potently prevented the delayed death of hippocampal neurons under both
      anesthetized and awake conditions. Even when HGF infusion started 6 hours after
      ischemia (i.e., in a delayed manner), HGF exhibited a neuroprotective action. We
      conclude that HGF, a novel neurotrophic factor, has a profound neuroprotective
      effect against postischemic delayed neuronal death in the hippocampus, which may
      have implications for the development of new therapeutic strategies for ischemic
      neuronal damage in humans.

PMID- 9538899
TI  - Epidermal growth factor protects neuronal cells in vivo and in vitro against
      transient forebrain ischemia- and free radical-induced injuries.
AB  - Epidermal growth factor (EGF) has been considered to be a candidate for
      neurotrophic factors on the basis of the results of several in vitro studies.
      However, the in vivo effect of EGF on ischemic neurons as well as its mechanism
      of action have not been fully understood. In the present in vivo study using a
      gerbil ischemia-model, we examined the effects of EGF on ischemia-induced
      learning disability and hippocampal CA1 neuron damage. Cerebroventricular
      infusion of EGF (24 or 120 ng/d) for 7 days to gerbils starting 2 hours before or
      immediately after transient forebrain ischemia caused a significant prolongation
      of response latency time in a passive avoidance task in comparison with the
      response latency of vehicle-treated ischemic animals. Subsequent histologic
      examinations showed that EGF effectively prevented delayed neuronal death of CA1
      neurons in the stratum pyramidale and preserved synapses intact within the strata
      moleculare, radiatum, and oriens of the hippocampal CA1 region. In situ detection
      of DNA fragmentation (TUNEL staining) revealed that ischemic animals infused with
      EGF contained fewer TUNEL-positive neurons in the hippocampal CA1 field than
      those infused with vehicle alone at the seventh day after ischemia. In primary
      hippocampal cultures, EGF (0.048 to 6.0 ng/mL) extended the survival of cultured
      neurons, facilitated neurite outgrowth, and prevented neuronal damage caused by
      the hydroxyl radical-producing agent FeSO4 and by the peroxynitrite-producing
      agent 3-morpholinosydnonimine in a dose-dependent manner. Moreover, EGF
      significantly attenuated FeSO4-induced lipid peroxidation of cultured neurons.
      These findings suggest that EGF has a neuroprotective effect on ischemic
      hippocampal neurons in vivo possibly through inhibition of free radical
      neurotoxicity and lipid peroxidation.

PMID- 9538900
TI  - Apolipoprotein E isoform-specific differences in outcome from focal ischemia in
      transgenic mice.
AB  - Apolipoprotein E (apoE), a 34-KD glycosylated lipid-binding protein, is expressed
      as three common isoforms in humans (E2, E3, or E4). Clinical evidence suggests
      that the apoE genotype (APOE) may be a risk factor for poor outcome after acute
      central nervous system injury. This was examined further in transgenic mice
      constructed with the human APOE3 or APOE4 gene under the control of human
      promoter and tissue expression elements. Presence of human apoE3 and apoE4
      proteins in brains of human APOE homozygous transgenic mice was confirmed by
      Western blotting. APOE3 (n = 12) and APOE4 (n = 10) mice underwent 60 minutes of
      middle cerebral artery occlusion. After 24-hour recovery, infarct size was
      measured. Infarct volumes (mean +/- standard deviation) were smaller in the APOE3
      group (cortex: APOE3 = 18 +/- 4 mm3; APOE4 = 30 +/- 11 mm3, P = 0.04; subcortex:
      APOE3 = 12 +/- 4 mm3; APOE4 = 18 +/- 4 mm3, P = 0.003). Hemiparesis was less
      severe in APOE3 mice (P = 0.02). These data indicate that human isoform-specific
      effects of apoE are relevant to acute pathomechanisms of focal ischemic brain
      damage when examined in the mouse. APOE transgenic mice may provide an
      appropriate model to examine the mechanistic basis for the differential effects
      of human apoE isoforms in acute central nervous system injury.

PMID- 9538901
TI  - A reproducible model of middle cerebral artery occlusion in mice: hemodynamic,
      biochemical, and magnetic resonance imaging.
AB  - A reproducible model of thread occlusion of the middle cerebral artery (MCA) was
      established in C57 Black/6J mice by matching the diameter of the thread to the
      weight of the animals. For this purpose, threads of different diameter (80 to 260
      microns) were inserted into the MCA of animals of different weights (18 to 33 g),
      and the success of vascular occlusion was evaluated by imaging the ischemic
      territory on serial brain sections with carbon black. Successful occlusion of the
      MCA resulted in a linear relationship between body weight and thread diameter (r
      = 0.46, P < 0.01), allowing precise selection of the appropriate thread size.
      Laser-Doppler measurements of CBF, neurological scoring, and 2,3,5
      triphenyltetrazolium chloride staining confirmed that matching of animal weight
      and suture diameter produced consistent cerebral infarction. Three hours after
      MCA occlusion, imaging of ATP, tissue pH, and cerebral protein synthesis allowed
      differentiation between the central infarct core, in which ATP was depleted, and
      a peripheral penumbra with reduced protein synthesis and tissue acidosis but
      preserved ATP content. Perfusion deficits and ischemic tissue alterations could
      also be detected by perfusion- and diffusion-weighted magnetic resonance imaging,
      demonstrating the feasibility of dynamic evaluations of infarct evolution. The
      use of multiparametric imaging techniques in this improved MCA occlusion model
      opens the way for advanced pathophysiological studies of stroke in gene
      manipulated animals.

PMID- 9538902
TI  - Hypoxia-ischemia induces a rapid elevation of ubiquitin conjugate levels and
      ubiquitin immunoreactivity in the immature rat brain.
AB  - Postnatal rats at 7 and 21 days of age were subjected to unilateral hypoxia
      ischemia (H/I) by right carotid artery ligation followed by 1.5 to 2 hours of
      hypoxia (8% oxygen). Brains were frozen at specific intervals of recovery from 0
      to 24 hours. Western blots of samples of right and left forebrain were
      immunodeveloped with a monoclonal antibody specific for ubiquitin, RHUb1. An
      elevation of ubiquitin conjugate levels in the right compared with the left
      forebrain of 7-day-old animals was detectable immediately following H/I and
      increased by close to 60% of control level within 1 hour of recovery. The
      conjugate immunoreactivity remained at this level for 6 hours but had declined to
      control levels by 24 hours of recovery. No such increase was observed in response
      to hypoxia alone. Similar changes were observed in samples from the 21-day-old
      rat brain. However, the elevation of ubiquitin conjugate levels was of slower
      onset and persisted longer than observed for the 7-day-old animals.
      Immunocytochemical studies of brain fixed by immersion in
      formaldehyde/acetone/methanol showed that ubiquitin-like immunoreactivity was
      increased in the right, but not left, cerebral cortex and hippocampus of animals
      subjected to H/I. The data suggest that elevated ubiquitination may represent a
      neuroprotective response to H/I.

PMID- 9538903
TI  - Metyrapone reduces rat brain damage and seizures after hypoxia-ischemia: an
      effect independent of modulation of plasma corticosterone levels?
AB  - Hypoxia-ischemia is accompanied by abundant corticosterone secretion that could
      exacerbate brain damage after the insult. The authors demonstrate that the
      steroid synthesis inhibitor metyrapone (150 mg/kg subcutaneously) suppresses the
      hypoxia-ischemia-induced rise of plasma corticosterone levels (17.3 +/- 3.6
      micrograms/dL) when compared with corticosterone-treated animals (72.2 +/- 4.8
      micrograms/dL) immediately after hypoxia-ischemia. In parallel, metyrapone
      reduced brain damage (P < 0.05). Moreover, none of the metyrapone-treated animals
      displayed seizures, whereas seven of eight corticosterone-treated animals had
      seizures after hypoxia-ischemia. Although corticosterone administration in
      metyrapone-treated animals elevated plasma corticosterone levels (39.0 +/- 5.3
      micrograms/dL), this did not result in a subsequent increase in brain damage and
      seizures when compared with metyrapone-treated animals. The authors conclude that
      metyrapone reduces brain damage and the incidence of seizures after hypoxia
      ischemia but that this effect might partially be independent from its effect on
      modulating plasma corticosterone levels.

PMID- 9538904
TI  - Effect of decreased glucose concentration on cerebrovascular tone in vitro.
AB  - We studied the effect of decreased glucose concentration on cerebrovascular tone
      in vitro. Segments of rat middle cerebral arteries (MCA) were isolated,
      cannulated at both ends with glass micropipettes, and pressurized to 85 mm Hg.
      Decreasing the glucose in the extraluminal bath and luminal perfusate from 5.5
      mmol/L to 1.0 or 0.5 mmol/L for 1.5 hours each had no significant effect on the
      diameter of the arteries. When all the glucose was removed from the extraluminal
      bath and luminal perfusate for 1.5 hours, the MCA dilated by 23% [252 +/- 24 (SD)
      microns to 311 +/- 7 microns (P < .5, n = 7)]. This dilation was 80% of the
      maximum dilation produced by removal of Ca+2 from the bathing solutions. Neither
      removal of the endothelium nor inhibition of the ATP-sensitive K channels with
      10(-5) mol/L glibenclamide altered the response of the isolated MCA to the
      removal of glucose. We conclude that rat MCA are relatively more resistant to
      substrate limitation compared to the brain as a whole.

PMID- 9538905
TI  - Evidence that functional glutamate receptors are not expressed on rat or human
      cerebromicrovascular endothelial cells.
AB  - Excitatory amino acids can modify the tone of cerebral vessels and permeability
      of the blood-brain barrier (BBB) by acting directly on endothelial cells of
      cerebral vessels or indirectly by activating receptors expressed on other brain
      cells. In this study we examined whether rat or human cerebromicrovascular
      endothelial cells (CEC) express ionotropic and metabotropic glutamate receptors.
      Glutamate and the glutamate receptor agonists N-methyl-d-aspartate (NMDA), alpha
      amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA), and kainate failed to
      increase [Ca2+]i in either rat or human microvascular and capillary CEC but
      elicited robust responses in primary rat cortical neurons, as measured by fura-2
      fluorescence. The absence of NMDA and AMPA receptors in rat and human CEC was
      further confirmed by the lack of immunocytochemical staining of cells by
      antibodies specific for the AMPA receptor subunits GluR1, GluR2/3, and GluR4 and
      the NMDA receptor subunits NR1, NR2A, and NR2B. We failed to detect mRNA
      expression of the AMPA receptor subunits GluR1 to GluR4 or the NMDA receptor
      subunits NR1(1XX); NR1(0XX), and NR2A to NR2C in both freshly isolated rat and
      human microvessels and cultured CEC using reverse transcriptase polymerase chain
      reaction (RT-PCR). Cultured rat CEC expressed mRNA for KA1 or KA2 and GluR5
      subunits. Primary rat cortical neurons were found to express GluR1 to GluR3 and
      NR1, NR2A, and NR2B by both immunocytochemistry and RT-PCR and KA1, KA2, GluR5,
      GluR6, and GluR7 by RT-PCR. Moreover, the metabotropic glutamate receptor agonist
      1-amino-cyclopentyl-1S, 3R-dicorboxylate (1S,3R-trans-ACPD), while eliciting both
      inositol trisphosphate and [Ca2+]i increases and inhibiting forskolin-stimulated
      cyclic AMP in cortical neurons, was unable to induce either of these responses in
      rat or human CEC. These results strongly suggest that both rat and human CEC do
      not express functional glutamate receptors. Therefore, excitatory amino acid
      induced changes in the cerebral microvascular tone and BBB permeability must be
      affected indirectly, most likely by mediators released from the adjacent
      glutamate-responsive cells.

PMID- 9538906
TI  - Reperfusion after thrombolytic therapy of embolic stroke in the rat: magnetic
      resonance and biochemical imaging.
AB  - The effect of thrombolytic therapy was studied in rats submitted to
      thromboembolic stroke by intracarotid injection of autologous blood clots.
      Thrombolysis was initiated after 15 minutes with an intracarotid infusion of
      recombinant tissue-type activator (10 mg/kg body weight). Reperfusion was
      monitored for 3 hours using serial perfusion- and diffusion magnetic resonance
      imaging, and the outcome of treatment was quantified by pictorial measurements of
      ATP, tissue pH, and blood flow. In untreated animals, clot embolism resulted in
      an immediate decrease in blood flow and a sharp decrease in the apparent
      diffusion coefficient (ADC) that persisted throughout the observation period.
      Thrombolysis successfully recanalized the embolized middle cerebral artery origin
      and led to gradual improvement of blood flow and a slowly progressing reversal of
      ADC changes in the periphery of the ischemic territory, but only to transient and
      partial improvement in the center. Three hours after initiation of thrombolysis,
      the tissue volume with ADC values less than 80% of control was 39 +/- 22% as
      compared to 61 +/- 20% of ipsilateral hemisphere in untreated animals (means +/-
      SD, P = .03) and the volume of ATP-depleted brain tissue was 25 +/- 31% as
      compared to 46 +/- 29% in untreated animals. Recovery of ischemic brain injury
      after thromboembolism is incomplete even when therapy is started as early as 15
      minutes after clot embolism. Possible explanations for our findings include
      downstream displacement of clot material, microembolism of the vascular
      periphery, and events associated with reperfusion injury.

PMID- 9538907
TI  - Autoregulatory vasodilation of parenchymal vessels is impaired during cerebral
      vasospasm.
AB  - Impaired CBF autoregulation during vasospasm after aneurysmal subarachnoid
      hemorrhage (SAH) could reflect impaired capacity of distal vessels to dilate in
      response to reduced local perfusion pressure or simply indicate that the
      perfusion pressure distal to large arteries in spasm is so low that vessels are
      already maximally dilated. Autoregulatory vasodilation can be detected in vivo as
      an increase in the parenchymal cerebral blood volume (CBV). Regional CBV, CBF,
      and oxygen extraction fraction in regions with and without angiographic vasospasm
      obtained from 29 positron emission tomography studies performed after
      intracranial aneurysm rupture were compared with data from 19 normal volunteers
      and five patients with carotid artery occlusion. Regional CBF was reduced
      compared to normal in regions from SAH patients with and without vasospasm as
      well as with ipsilateral carotid occlusion (P < .0001). Regional oxygen
      extraction fraction was higher during vasospasm and distal to carotid occlusion
      than both normal and SAH without vasospasm (P < .0001). Regional CBV was reduced
      compared to normal in regions with and without spasm, whereas it was increased
      ipsilateral to carotid occlusion (P < .0001). These findings of reduced
      parenchymal CBV during vasospasm under similar conditions of tissue hypoxia that
      produce increased CBV in patients with carotid occlusion provide evidence that
      parenchymal vessels distal to arteries with angiographic spasm after SAH do not
      show normal autoregulatory vasodilation.

PMID- 9538908
TI  - Absolute cerebral blood flow and blood volume measured by magnetic resonance
      imaging bolus tracking: comparison with positron emission tomography values.
AB  - The authors determined cerebral blood flow (CBF) with magnetic resonance imaging
      (MRI) of contrast agent bolus passage and compared the results with those
      obtained by O-15 labeled water (H215O) and positron emission tomography (PET).
      Six pigs were examined by MRI and PET under normo- and hypercapnic conditions.
      After dose normalization and introduction of an empirical constant phi Gd,
      absolute regional CBF was calculated from MRI. The spatial resolution and the
      signal-to-noise ratio of CBF measurements by MRI were better than by the H215O
      PET protocol. Magnetic resonance imaging cerebral blood volume (CBV) estimates
      obtained using this normalization constant correlated well with values obtained
      by O-15 labeled carbonmonooxide (C15O) PET. However, PET CBV values were
      approximately 2.5 times larger than absolute MRI CBV values, supporting the
      hypothesized sensitivity of MRI to small vessels.

PMID- 9538909
TI  - Positron emission tomography [15O]water studies with short interscan interval for
      single-subject and group analysis: influence of background subtraction.
AB  - Use of short interscan interval [15O]water positron emission tomography (PET)
      studies reduces the overall study duration and may allow an increased number of
      scans for single-subject analysis of unique cases (e.g., stroke). The purpose of
      this study was to examine how subtraction of residual radioactivity from the
      previous injection (corrected scan) compared to nonsubtraction (uncorrected scan)
      in a PET short interscan interval (6 minutes) study affects single-subject and
      group data analysis using a motor activation task. Two currently widely used
      analytic strategies, Worsley's method and the SPM technique, were applied.
      Excellent agreement between activation maps obtained from corrected and
      uncorrected data sets was obtained both in single-subject analyses performed on
      data sets from the six normal subjects and three stroke (subcortical infarct)
      patients, and in group analysis (six normal subjects) within a particular
      statistical method. The corrected and uncorrected data were very similar in the
      (1) number of activated brain regions; (2) size of clusters of activated brain
      voxels; (3) Talairach coordinates of the activated region; and (4) t or Z value
      of the peak intensity for every significantly activated motor brain structure
      (both for large activations such as in motor cortex and small activations such as
      in putamen and thalamus). [15O]Water PET data obtained with a short interscan
      interval (6 minutes) produce similar results whether or not the background is
      subtracted. Thus, if injection dose and timing are constant, one can achieve the
      advantage of a short interscan interval without the added complexity of
      correcting for background radioactivity.

PMID- 9538910
TI  - Noninvasive measurement of regional cerebral blood flow by near-infrared
      spectroscopy and indocyanine green.
AB  - Clinicians lack a practical method for measuring CBF rapidly, repeatedly, and
      noninvasively at the bedside. A new noninvasive technique for estimation of
      cerebral hemodynamics by use of near-infrared spectroscopy (NIRS) and an
      intravenously infused tracer dye is proposed. Kinetics of the infrared tracer
      indocyanine green were monitored on the intact skull in pigs. According to an
      algorithm derived from fluorescein flowmetry, a relative blood flow index (BFI)
      was calculated. Data obtained were compared with cerebral and galeal blood flow
      values assessed by radioactive microspheres under baseline conditions and during
      hemorrhagic shock and resuscitation. Blood flow index correlated significantly
      (rs = 0.814, P < 0.001) with cortical blood flow but not with galeal blood flow
      (rs = 0.258). However, limits of agreement between BFI and CBF are rather wide
      (+/- 38.2 +/- 6.4 mL 100 g-1 min-1) and require further studies. Data presented
      demonstrate that detection of tracer kinetics in the cerebrovasculature by NIRS
      may serve as valuable tool for the noninvasive estimation of regional CBF.
      Indocyanine green dilution curves monitored noninvasively on the intact skull by
      NIRS reflect dye passage through the cerebral, not extracerebral, circulation.

PMID- 9538911
TI  - Brain correlates of memory processes in patients with dementia of Alzheimer's
      type: a SPECT Activation Study.
AB  - Task-induced changes in regional cerebral blood flow (rCBF) during verbal
      episodic memory activation were compared in 17 right-handed patients with
      dementia of the Alzheimer's type (DAT) and 20 healthy volunteers. Regional
      cerebral blood flow was assessed using single photon emission computed tomography
      (SPECT) and an injection of 133Xe (xenon, isotope of mass 133) in 21 regions of
      interest (ROI) during rest, passive listening to 36 words, and memorizing of a 12
      word list repeated three times. In healthy subjects, memory-listening comparison
      showed activation of a distributed system involving several left-sided ROI,
      especially the posterior inferior frontal region. In patients with DAT, the same
      pattern of activation was found for listening-rest comparison, and no significant
      changes were found in memory-listening comparison. During listening compared with
      rest, significant activation was observed in left-sided hypoperfused regions. A
      significant correlation between memory performance and rCBF recorded in patients
      with DAT during the memory task was found only in the right lateral frontal
      region, a region that was not hypoperfused significantly in patients. The
      involvement of this region might relate to either retrieval effort or actual
      performance of patients with DAT on the memory task.

PMID- 9538912
TI  - Laparoscopic Toupet fundoplication: prospective study of 100 cases. Results at
      one year and literature review.
AB  - We report a prospective evaluation of 100 patients who underwent laparoscopic
      fundoplication according to Toupet. All these cases where suffering from gastro
      oesophageal reflux resistant to medical treatment or recurring after stopping it.
      Only one conversion into laparotomy was required. Perioperative morbidity (4%),
      mortality (0%), median hospital stay (4 days) and return to work (3 weeks) were
      lower than in case of open surgery in the literature. One year after the
      operation, clinical results were similar to those of laparotomy with 93% of
      patients free of symptoms. Excellent results of this technique lead us to assert
      that laparoscopic Toupet procedure is an interesting way of treating the gastro
      oesophageal reflux that does not respond to medical treatment.

PMID- 9538913
TI  - Reconstruction of neck burns. A long-term comparative study between skin grafts,
      skin expansion and free flaps.
AB  - Cervical reconstruction after postburn scarring remains a challenge for the
      plastic surgeon. Several well-known procedures are possible: split or full
      thickness skin grafts, local flaps, free skin flaps, expanded skin,... In order
      to evaluate each technique, three procedures are compared with a long-term follow
      up (> or = 1 year): skin expansion, free flap surgery and full-thickness skin
      grafting. Fifteen patients are reviewed, with five patients operated according to
      each method. In this study, each burn patient was suffering from a severe neck
      burn contracture, restricting the neck motility to a few degrees. These patients
      were operated on by different surgeons, according to their personal indications.
      The full-thickness skin graft is usually harvested from the abdomen (by means of
      a miniabdominoplasty) and is applied under a tie-over dressing. This simple
      procedure has few complications and gives satisfactory results. Skin expansion
      provides a good texture and color matching but has a higher morbidity and
      necessitates several procedures. Free flap surgery is time-consuming, gives a
      good functional result but poor cosmetic aspect (different colour, excessive
      bulk). Comparing the functional and aesthetic result of the three types of
      reconstruction in terms of morbidity, neck mobility, skin elasticity, skin
      sensitivity, matching and scar recurrence, full-thickness skin grafting seems to
      be the most adequate technique.

PMID- 9538914
TI  - Ectopic prolactinoma in the clivus.
AB  - BACKGROUND: Ectopic pituitary adenomas are rare. Only 29 cases are reported in
      the literature. The clivus was involved in some cases but sella turcica was
      occasionally involved. CLINICAL PRESENTATION: Headache was the first symptom of a
      47-year-old woman. Radiological examination diagnosed a clivus tumour. No
      connection with the pituitary gland was observed. Pre-operative diagnosis was
      metastasis of an unknown cancer. INTERVENTION: By a transphenoidal approach, we
      removed a haemorrhagic tumour. No connection between the normal pituitary gland
      and the tumour was observed. Neuropathological analysis showed a prolactinoma.
      CONCLUSION: We report a rare case of an ectopic prolactinoma in the clivus
      unrelated to the pituitary gland. Only one other case has been reported in the
      literature.

PMID- 9538915
TI  - The venous thrombectomy: obsolete or forgotten?
AB  - This report describes the surgical management of three patients with an extended
      ilio-femoral deep venous thrombosis. In the first patient a residual occlusion of
      the common iliac vein was treated conservatively and this patient developed
      severe chronic venous insufficiency. In the second patient a residual
      (sub)occlusion of the common iliac vein was treated with a stent and this patient
      remained asymptomatic with two years follow-up. In the third patient no residual
      or underlying anatomical abnormality was found with a good result at one year.
      Venous thrombectomy still has a place in the treatment of deep venous thrombosis
      and the long term results may be improved by application of endovascular
      techniques.

PMID- 9538916
TI  - Does the intrapelvic compartment syndrome exist?
AB  - Pelvic compartment syndrome is a rare condition. As in other musculoskeletal
      localizations, the intra-compartmental pressure raises above a critical level. In
      the pelvic compartment syndromes, the gluteal compartments are mainly concerned.
      We report on three patients with bilateral ureteral obstruction, due to
      compression by a massive retroperitoneal haematoma as a complication of an
      unstable pelvic ring or acetabular fracture. Anuria with renal organ failure, due
      to compression of the ureters in the small true pelvis represents an intrapelvic
      compartment syndrome. Anuria, due to ureteral compression, mostly developing 24
      to 48 hours after injury, has to be differentiated from anuria due to
      hypovolaemic shock or lesions of the lower urine tract. Bilateral tube
      nephrostomy represents a temporary and suboptimal therapy. Treatment of the
      intrapelvic compartment syndrome consists in fracture stabilization and surgical
      revision of the retroperitoneal space, including evacuation of the haematoma and
      decompression of the ureters, as it was performed in our patients. Persistent
      isolated bleeding points can be ligated. If the patient is haemodynamically
      stable, internal fracture fixation can be performed during the same operative
      session. A second look procedure may be required for prevention of septic
      complications.

PMID- 9538917
TI  - Declaration of the promotion of patient's rights in Europe (partim). World Health
      Organization--Europe, 1994.

PMID- 9538918
TI  - [The surgeon and the law. Legal responsibility. Significance of a contract which
      has performance of medical acts as object].

PMID- 9538919
TI  - [Liability of the hospital for intramural surgical activities].

PMID- 9538920
TI  - [Ethical aspects of informed consent].

PMID- 9538921
TI  - [Code of conduct in the event of a significant error or incident].

PMID- 9538922
TI  - [Minimal requirements for MR diagnosis of the brain for clarification of
      nonspecific neurological symptoms].
AB  - The main tasks of MRI diagnosis of the brain for unspecific neurological symptoms
      such as, for example, headache, psychiatric diseases, subjective cognitive
      deficits, and retarded development in children generally involve the reliable
      exclusion of morphologically detectable lesions. Since there can be no
      universally accepted protocol for all possible situations, a basis protocol is
      given under consideration of modern fast spin echo, turbo FLAIR, and T2*-weighted
      gradient echo sequences to obtain important information in a short time. In
      addition, useful supplements are suggested that can proved further relevant data
      in dependence on the respective condition.

PMID- 9538923
TI  - [Recent developments and applications of MRI sequence technique. I: turbo spin
      echo, HASTE, turbo inversion recovery, turbo gradient echo, turbo gradient spin
      sequences].
AB  - Goal of this two-part report is to provide clinical MRI radiologists with a guide
      to the world of new and clinically available MRI pulse sequences. Discussed are
      the principles of rapid scan techniques like multiple spin-echo imaging, multiple
      gradient echo imaging, echo planar imaging, diffusion and perfusion imaging, and
      future perspectives (review article).

PMID- 9538924
TI  - [Principles in the assessment of radiation exposure in interventional measures].
AB  - Interventional procedures undoubtedly involve a high radiation exposure, for the
      patient. For some interventional procedures the frequencies of procedures,
      radiation exposures and considerations to the radiation risk are shown and
      discussed. Radiation risk is calculated with the currently common assumptions but
      always in consideration of the age and expectation of life of the patient. The
      risk coefficient used for the age-distribution of the common population is 5% per
      Sv, but for the risk coefficient for, e.g., the group of PTA patients 1.0% per Sv
      can be derived. That's why the risk of cancer increases in this patient group by
      5/100,000. This risk must be balanced with the immediate benefit and the risk of
      alternative procedures.

PMID- 9538925
TI  - [Single shot MRI cholangiopancreatography (MRCP) with a "fast acquisition spin
      echo" sequence (FASE). Replacement of ERCP?].
AB  - PURPOSE: 118 Patients with suspected obstruction of the biliary tract of
      pancreatic duct were examined to evaluate the accuracy of MR
      cholangiopancreatography (MRCP) in comparison with diagnostic findings in
      endoscopic retrograde cholangiopancreatography (ERCP). METHODS: Using a 0.5-Tesla
      MR imaging system (FLEXART, Toshiba) and a QD body-coil, a recently developed
      heavily T2-weighted fast acquisition spin echo sequence (FASE) was applied. In
      this FASE sequence two significant features are implemented. A fast spin-echo
      (SE) sequence allows a large number of echos and conjugate K-space filling speeds
      up data acquisition. Thus, the acquisition time of single-shot breath-hold images
      takes only 3 seconds, which makes MRCP a feasible technique even in elderly or
      suffering patients. There is no need for time-consuming postprocessing
      procedures. RESULTS: In all MRCP examinations images of satisfactory quality were
      obtained. In cases of obstruction of the biliary or pancreatic duct, locations
      and lengths of stenoses were correctly demonstrated. Gallstones within the
      gallbladder or in the extrahepatic bile ducts were also properly visualised in
      MRCP. Stenoses caused by non-depicted pancreatic carcinoma, gallbladder
      carcinoma, or segmental pancreatitis were reliably shown. CONCLUSION: Even if
      MRCP will not replace ERCP, a number of clinical applications for non-invasive
      MRCP examination arise: primary diagnosis in patients with obstructive jaundice,
      obstruction of the biliary or pancreatic duct, if ERCP is not possible due to
      anatomic reason and in patients scheduled for laparoscopic cholecystectomy.

PMID- 9538926
TI  - [Diagnosis of pneumonia in long-term ventilated patients. Value of digital
      luminescence radiography in comparison with clinical and microbiological
      monitoring].
AB  - PURPOSE: Pulmonary infection is one of the most feared complications in patients
      receiving long-term ventilation. We evaluated prospectively the diagnostic value
      of daily bedside chest radiography performed as digital luminescence radiography
      (DLR) in comparison to clinical findings and quantitative microbial culture.
      MATERIAL AND METHODS: Prospective evaluation of daily bedside chest radiography
      (DLR) and clinical parameters such as blood count, body temperature, and
      microbiological monitoring (quantitative culturing, microscopy) of 20 patients
      receiving long-term ventilation was undertaken. Altogether 325 chest radiographs
      were evaluated. RESULTS: 96% of the routine radiographs showed abnormal findings.
      Nosocomial pneumonia was suspected in 31% of all 330 days of observation by means
      of clinical and microbiological findings. DLR showed correct findings in 80% of
      this days (right-positive interpretation); a false-positive interpretation was
      resulted in 16 radiographs. Most common finding in nosocomial pneumonia was an
      alveolar pattern with air bronchogram. Fever and leucocytosis often precede
      radiological evidence of pneumonia. CONCLUSION: Daily bedside chest radiography
      performed as DLR shows abnormal finding in a high percentage. Bedside chest
      radiograph is in accordance to clinical and microbiological finding of nosocomial
      pneumonia in 80%.

PMID- 9538927
TI  - [Optical mammography in preoperative patients].
AB  - AIM: Research concerning alternative methods of breast imaging that may
      supplement or even replace mammography appears interesting for further
      improvement of diagnostic accuracy, for possible cost reduction and increased
      patient acceptance and compliance. METHOD/PATIENTS: 119 pre-operative patients
      (59 carcinomas, 60 benign lesions) were examined on a prototype breast scanner in
      this fundamental research project. Images of the compressed breast that display
      light transmission and phase shift at wavelengths of 690, 750, 790 and 860 nm
      were obtained with scanning steps every 2 mm. Based on these images we could
      calculate further images. RESULTS: Images displaying the division of two original
      transmission images appeared most useful, whereas phase images generally did not
      yield relevant additional information. A total of 51 out of 59 carcinomas (mean
      diameter: 21 mm) were visualised and diagnosed. Specificity in respect of lesion
      diagnosis was 28%. If surrounding tissue was included in the evaluation, the
      specificity dropped to 9%. DISCUSSION: The method is not sufficiently developed
      and well-tried for clinical use. Future research might consider the development
      of tumour-specific contrast media.

PMID- 9538928
TI  - [Possibilities for dose reduction in coronal spiral CT of the mid-face area].
AB  - The radiation dose at the eye lens and the thyroid gland in spiral-CT
      examinations is comparable to those known from conventional computed tomography.
      In view of an increasing artificial radiation exposure, it remains an important
      aim to achieve dose reduction with persistent adequate imaging quality. We
      determined the doses of the named organs in four different CT-examination
      protocols by use of phantom studies and in 45 patients. By reduction of tube
      current and tube voltage, organ doses can be reduced by half. This is achieved
      without a relevant loss in diagnostic precision as far as high-contrast
      structures are concerned. Compared to conventional CT-scanning, the dose
      reduction reached 75%. Taking into consideration the increasing insensitivity in
      the z-plane and the worsening of the section-sensitivity profile, a properly
      chosen increase in pitch may result in a significant dose reduction. CT-scanning
      of high-contrast structures in the head and neck can and should be performed with
      the least radiation exposure possible.

PMID- 9538929
TI  - [Case report of a large lipomatous soft tissue tumor].
AB  - A case of diffuse infiltrating lipomatosis is reported. This entity represents a
      particular type of lipoma. It can be distinguished from other fatty tumors by its
      localisation, extent, therapeutic procedure, and prognosis. Magnetic resonance
      imaging (MRI) enables the differentiation from lipomatosis pelvis and malignant
      tumors as well. Histopathological examination, however, is necessary to exclude
      liposarcoma. Further growth or recurrence of diffuse infiltrating lipomatosis can
      be detected by MRI follow-up examinations.

PMID- 9538930
TI  - [Intrafascial hematoma of the rectus abdominis muscle as a complication after
      laparoscopic operations].
AB  - We report on two patients with intrafascial hematoma of the musculus rectus
      abdominis following laparoscopic operations. One patient was operated on a
      stenosis of the common iliac artery for an aortofemoral bypass. The other patient
      was operated on an inguinal hernia. Only a CT scan of the abdomen led to the
      correct diagnosis, because the use of ultrasound was limited by pneumoperitoneum
      and bandages, and retroperitoneal bleeding could not be recognized. Computed
      tomography is a valid method for detecting this complication of laparoscopic
      surgery.

PMID- 9538931
TI  - Heart failure: is there an energy deficit contributing to contractile
      dysfunction?
AB  - Alterations in myocardial energy metabolism have been demonstrated in both animal
      experiments and clinical observations. Whether these changes contribute to heart
      failure has been a longstanding and controversial issue. I. The creatine kinase
      (CK) system and the high energy phosphates under physiological conditions and in
      acute heart failure: 1. According to in vivo and in vitro experiments the
      myocardial creatine/creatine phosphate (Cr/CP) system is directly linked to
      mitochondrial oxidative phosphorylation via the mitochondrial CK. 2. The shift in
      the mass action ratio of the CK reaction with increasing myocardial oxygen
      consumption enables marked stimulation of mitochondrial respiratory function via
      the Cr/CP system with almost maintained free energy of the adenosine
      triphosphate/adenosine diphosphate (ATP/ADP) system. 3. In acute heart failure
      the depressed myocardial content mainly of CP can be considered as an adaptive
      mechanism related to increased oxygen demands. II. The CK system and the high
      energy phosphates in chronic heart failure: 1. The alterations observed in the CK
      system in chronic heart failure cannot be interpreted in terms of an "energy
      deficit" (i.e., the excess of what is spent over what is received on energy). 2.
      "Energy reserve" (i.e., energy kept back for future use, to fill an emergency) is
      markedly reduced in heart failure. 3. Under steady state conditions decreased
      "energy reserve" cannot be expected to contribute to heart failure. Under stress
      conditions, however, this mechanism is manifest by reducing contractile reserve.
      4. The mechanisms by which decreased "energy reserve" induces depression of
      contractile reserve is not elucidated. III. Heart failure related to alterations
      in energy metabolism (mitochondrial diseases, stunned, and hibernating
      myocardium): 1. The phenotype of mitochondrial diseases is predominantly
      determined by neurological disorders and myopathies. Therefore, the patients are
      rarely referred to a cardiologist, although the cardiac involvement may
      ultimately determine the patients' prognosis. 2. Stunned and hibernating
      myocardium are characterized by prolonged contractile dysfunction in the presence
      of reversibly damaged myocardium. The underlying mechanisms and its triggers are
      unknown. INTERPRETATIONS: 1. The reduced energy reserve in heart failure may be
      considered to contribute to the progression of the disease. 2. As an alternative,
      however, it can likewise represent a mechanism to protect the endangered
      myocardium from overload.

PMID- 9538932
TI  - Glucocorticoids and protein kinase C regulate neutral endopeptidase 24.11 in
      human vascular smooth muscle cells.
AB  - Neutral endopeptidase 24.11 (NEP) degrades vasoactive peptides, including
      natriuretic peptides, kinins, angiotensins, and endothelins. It contributes to
      the regulation of vascular tone and body fluid homeostasis. In the present study
      the expression of NEP was investigated in cultured human smooth muscle cells
      derived from umbilical veins (HSMC) and human coronary arteries (HCSMC). A
      constitutive NEP expression was found in growing and starved smooth muscle cells
      and was about 4 fold higher than in endothelial cells derived from umbilical
      veins. Treatment of smooth muscle cells with dexamethasone (0.01-0.1 microM Dex)
      and with the protein kinase C activator, phorbol myristate acetate (0.1 microM
      PMA), increased NEP mRNA by 3-4 fold and two fold, respectively. Dexamethasone
      (0.1 microM) and prednisolone (0.1 microM) increased protein concentrations of
      NEP and NEP-activity after 3 days and continued to increase at 5 days, whereas
      PMA induced maximal increase of NEP concentrations after 48 hours. The effect of
      dexamethasone was concentration-dependent and was completely abolished by
      cycloheximide (10 microM), a protein synthesis inhibitor. The effect of PMA on
      NEP protein was completely blocked by protein kinase C inhibitors, calphostin C
      and H7 (both 10 microM). NEP 24.11 is constitutively expressed in human smooth
      muscle cells from umbilical veins and coronary arteries and is upregulated by
      glucocorticoids and by protein kinase C activation in these cells.

PMID- 9538933
TI  - The arterial length-densities under preventive angiotensin-converting-enzyme
      inhibiting treatment in the myocardium of spontaneously hypertensive rats.
AB  - The length density (Lv) of capillaries is known to be increased in the hearts of
      spontaneously hypertensive rats (SHR) after high-dosed but also after low-dosed
      subantihypertensive treatment with the ACE-inhibitor Ramipril administered in
      utero and post partum. Under the same conditions in the present study only high
      dose Zabicipril caused an increase of capillary Lv. Under preventive ACE
      inhibition in both high-dose groups Lv of myocardial arteries was significantly
      higher. In the low-dose groups Lv was not significantly increased. The increased
      arterial Lv in the high-dose-group may result from the avoidance of angiotensin
      II-induced overabundant growth of myocardial muscle-mass. Changes in collagen
      could not be found in any of the experimental groups.

PMID- 9538934
TI  - Extracellulary administered lysophosphatidylcholine causes Ca2+ efflux from
      freshly isolated adult rat cardiomyocytes.
AB  - It has previously been reported that ischemia and reperfusion of the heart cause
      accumulation of lysophosphatidylcholine (LPC) within the myocardium. While it is
      known that LPC causes the transient increase of intracellular free Ca2+
      concentration ([Ca2+]i) during contraction of cardiac cells, little is known
      about the mechanism for decreasing [Ca2+]i in cardiomyocytes during LPC
      accumulation. Since cumulative elevation in [Ca2+]i leads to irreversible injury
      to cardiomyocytes, elevated [Ca2+]i must be restored to an unstimulated level to
      maintain cell functions. In the present study, we therefore examined the effect
      of LPC on Ca2+ efflux from freshly isolated adult rat cardiomyocytes. LPC
      stimulated the efflux of 45Ca2+ from the cells in a concentration-dependent
      manner (10(-7)M-10(-5)M). Other lysophospholipids, which are generated from
      phospholipids of the cell membrane, failed to induce 45Ca2+ efflux from the
      cells. Dilazep and K-7259, which are known to inhibit the increase in [Ca2+]i
      caused by LPC, likewise reduced 45Ca2+ efflux caused by LPC addition.
      Furthermore, the LPC-stimulated 45Ca2+ efflux was not affected by removal of
      extracellular Ca2+, but was dependent on the presence of extracellular Na+. On
      the other hand, inhibitors of Na+/Ca2+ exchange, amiloride and 5-(N,N-dimethyl)
      amiloride, inhibited LPC induced 45Ca2+ efflux. These results suggest that LPC
      stimulates extracellular Na(+)-dependent 45Ca2+ efflux from freshly isolated
      adult rat cardiomyocytes, probably through Na+/Ca2+ exchange on the plasma
      membrane of the cells.

PMID- 9538935
TI  - Effect of basic fibroblast growth factor on angiogenesis in the infarcted porcine
      heart.
AB  - Administration of growth factors is emerging as a new therapeutic approach for
      the enhancement of collateral vessel formation in the ischemic heart. We have
      investigated the effects of intramyocardial delivery of FGF-2 in the presence and
      absence of heparin on angiogenesis in a porcine model of myocardial infarction.
      Yorkshire pigs were subjected to myocardial infarction by the placement of an
      embolization coil in the left anterior descending artery (n = 5). Four to five
      weeks after creation of an infarct, FGF-2 (10 micrograms) alone or in complex
      with heparin, heparan sulfate, or heparin agarose beads was injected either into
      the normal myocardium or along the infarct border area. Histologic evaluation of
      each injection site was performed 4 to 5 weeks post-injection. The effect of FGF
      2 on angiogenesis was evaluated by determining the number of capillaries
      (diameter < 20 microns (and arterioles (> 20 microns with tunica media) in each
      area observed. The number of capillaries were not affected by the treatment of
      FGF-2 both in normal myocardium and infarct border area. However, in the normal
      myocardium, the number of arterioles were increased with the treatment of FGF-2
      alone (85 +/- 59%, P < 0.04), FGF-2 plus heparin (281 +/- 193%, P < 0.004) and
      FGF-2-coated heparin beads (241 +/- 141%, P < 0.01), as compared to control.
      Delivery of FGF-2 into the infarct border area, also increased the number of
      arterioles when FGF-2 was given with heparin (736 +/- 154%, P < 0.001) or heparin
      beads (700 +/- 109%, P < 0.001), as compared to control. FGF-2 administered with
      heparin was the most effective method of enhancing angiogenesis as compared to
      FGF-2 alone, FGF-2 plus heparan sulfate, or FGF-2 coated heparin agarose beads.

PMID- 9538936
TI  - Characterization of metabolic responses to low-flow ischemia in intact pig hearts
      and isolated blood-perfused neonatal pig hearts.
AB  - There are different well established experimental models of low-flow ischemia. We
      examined metabolic variables during reduced coronary blood flow (CBF) in intact
      pig hearts and isolated neonatal pig hearts, producing similar degrees of
      postischemic dysfunction without infarction. The isolated hearts were perfused
      with red blood cell enriched buffer. In eight open-chest pigs mid-LAD flow was
      reduced to 70% for 60 min, followed by 120 min reperfusion. Myocardial segment
      lengths were recorded and regional coronary venous blood was sampled. In isolated
      piglet hearts CBF was reduced to 50% (n = 4), 25% (n = 4), and 10% (n = 17). Only
      when flow was reduced to 10% did hearts show signs of anaerobic metabolism.
      Mechanical function was recorded by a balloon in the left ventricle and coronary
      venous blood was sampled. Intact pig hearts showed release of protons, CO2, and
      lactate which peaked after 5-10 min of ischemia and thereafter stabilized at
      reduced levels. In contrast, in isolated neonatal hearts exposed to 10% CBF
      releases of protons, CO2, and lactate were stable during ischemia with no
      adaptational changes over time. In a separate group (n = 4), repetitive biopsies
      revealed no adaptational changes over time for adenosine triphosphate and
      creatine phosphate during 10% CBF. Contractile function was stably reduced during
      ischemia in both models. CONCLUSION: During reduced CBF "metabolic adaptation"
      occurs in intact pig hearts. In contrast, this feature is not present in isolated
      blood-perfused piglet hearts. The mechanisms responsible for these differences
      are uncertain. However, differences in metabolism between adult and neonatal
      hearts and different loading conditions during ischemia might contribute.

PMID- 9538937
TI  - Myosin heavy chain synthesis during the progression of chronic tachycardia
      induced heart failure in rabbits.
AB  - Chronic tachycardia causes LV dilatation and dysfunction, with no hypertrophy.
      However, the contributing mechanisms responsible for the left ventricular (LV)
      remodeling in the absence of myocardial growth in this model of heart failure
      remain unclear. Therefore, the goal of the present study was to serially examine
      changes in LV function, steady state myosin heavy chain (MHC) mRNA levels, in
      vivo synthesis rates, and abundance with the progression of chronic tachycardia
      induced heart failure. Adult rabbits (3.5-4.5 kg) were studied after one, two, or
      three weeks of pacing ventricular tachycardia (VT; 400 bpm) and in controls (n =
      6 for all groups). LV fractional shortening was reduced by 30% at week one and by
      over 50% at week three of chronic VT. End-diastolic dimension (EDD) increased at
      week two compared to controls (1.66 +/- 0.10 vs 1.35 +/- 0.11 cm, p < 0.05) and
      increased further at week three of VT (1.70 +/- 0.06 cm, p < 0.05). The
      progressive changes in LV geometry and function with chronic VT were not
      associated with concomitant time dependent changes in LV mass or MHC mRNA levels.
      In contrast, MHC fractional synthesis rates increased and reached statistical
      significance at week three of VT compared to controls (8.3 +/- 0.8 vs 5.5 +/-
      0.5%/day, p < 0.05). Despite the stable or increased MHC protein synthesis rates,
      there was no change in MHC protein abundance at any point during the progression
      of VT induced heart failure, implicating enhanced MHC protein degradation. Thus,
      this study demonstrated that a contributory mechanism for the LV remodeling and
      lack of myocardial growth, which occurs with VT induced heart failure, is
      enhanced contractile protein degradative processes.

PMID- 9538938
TI  - Measurement of left ventricular maximal isovolumetric pressure in rats: effects
      of antihypertensive drugs and diabetes mellitus.
AB  - We developed a method for measuring left ventricular maximal isovolumetric
      pressure (LVMIP) in intact rats and applied it in the presence of acutely
      administered antihypertensive drugs and in experimental diabetes mellitus. The
      combination of a 2 French Fogarty arterial embolectomy balloon catheter with a
      new ultra-thin shaft (0.25 mm diameter) Millar ultra-miniature pressure tip
      catheter was used. Closed-chest, thiopental anaesthetized female Sprague-Dawley
      rats received the beta-adrenoceptor blocker metoprolol (1 mg/kg/h), the alpha
      adrenoceptor blocker prazosin (0.1 mg/kg/h), and the calcium antagonist
      nifedipine (0.5 mg/kg/h). They were applied as continuous i.v. infusion for 30
      minutes. The angiotensin II type 1 (AT1) receptor antagonist losartan (3 mg/kg)
      was applied as bolus i.v. injection. Diabetes mellitus was induced by a single
      tail vein injection of streptozotocin (60 mg/kg) five weeks prior to hemodynamic
      measurements. Under control conditions, left ventricular systolic pressure (LVSP)
      was 136.5 +/- 3.7 mmHg and increased to 263 +/- 5.4 mmHg when the balloon was
      inflated (LVMIP). LVSP was significantly lower in the presence of prazosin,
      metoprolol, nifedipine, and in diabetic rats. However, LVMIP was significantly
      reduced only in the metoprolol-treated and diabetic rats. Both LVSP and LVMIP did
      not change significantly in losartan-treated rats. The degree of the increase in
      left ventricular maximal isovolumetric pressure during balloon inflation (LVMIP
      LVSP) was not significantly different in any experimental condition. These
      results suggest that the mechanism for evoking LVMIP is not dependent on the
      acute stimulation of cardiac alpha- and beta-adrenergic receptors, on calcium
      channels, nor on the AT1 receptors. In addition, the intrinsic mechanism for the
      generation of LVMIP seems not to be influenced in the diabetic state.

PMID- 9538939
TI  - Myocardial blood flow in awake dogs with chronic tricuspid regurgitation.
AB  - The primary purpose of this study was to define regional blood flow in dogs with
      chronic tricuspid regurgitation (TR) in order to determine if the marked
      hypertrophy of the right atria resulted in compromised myocardial perfusion.
      Myocardial blood flow (ml/min/gm) was measured with radiolabeled microspheres in
      eight dogs with TR during rest, moderate exercise (5 dogs), and infusion of
      adenosine (1 mg/kg/min), an index of minimal vascular resistance. Similar
      measurements were obtained in eight normal dogs. In TR, the ratio of right atrium
      (RA) and right ventricle (RV) to body weight was greater than in normal dogs, 77%
      and 30%, respectively. During rest, flow in the RA appendage was less than in
      nonappendage region in the normal dogs; no differences were noted in TR dogs,
      indicating an augmented hemodynamic role of the appendage in TR. Both RA and RV
      blood flow was greater in TR during rest but no other differences in flow were
      found between the two groups. Minimum vascular resistance in RV but not RA was
      slightly increased in TR versus normal. During marked myocyte hypertrophy, the
      vasculature of RA develops sufficiently to provide the same flow capacity as in
      the normal heart.

PMID- 9538940
TI  - In vitro dermal intoxication by bis(chloroethyl)sulfide. Effect on secondary
      epidermization.
AB  - Skin intoxication by bis(beta-chloroethyl)sulfide (BCES; sulfur mustard) induces
      cutaneous lesions similar to thermal burns, characterized by slowness of skin
      healing. We have developed an in vitro model of skin equivalent to investigate
      mechanisms involved in this delay. Direct intoxication of dermal equivalent
      produced dose- and time-dependent cytotoxicity. A decrease of macroscopic
      retraction of collagen gels was observed, parallel to the toxic concentration
      with, at histological level, absence of collagen fiber reorganization. Fibroblast
      synthesis of fibronectin was also inhibited by intoxication, as demonstrated at
      an immunobiochemical and immunohistochemical level. These dermal alterations were
      correlated with secondary modifications of epithelial maturation of
      nonintoxicated normal human keratinocytes. Cellular adhesion was perturbed, as
      visualized by a delay in expression and reorganization of basement membrane
      components, laminen, collagen IV, and fibronectin. Epidermal terminal
      differentiation was also affected, as shown by the absence of
      profilaggrin/filaggrin biosynthesis. We demonstrated in vitro, that direct dermal
      alterations secondarily induce disturbance of epithelial maturation. Taken
      together, these data show the fundamental role of dermal-epidermal interactions
      in a normal skin reconstruction. Clinical slowness of wound healing observed
      after cutaneous intoxication by BCES may thus be explained by direct alkylation
      of some structures and further disturbances of their biosynthesis.

PMID- 9538941
TI  - Antioxidant activity in alveolar epithelial type 2 cells of rats during the
      development of bleomycin injury.
AB  - Bleomycin (BLM) induces lung inflammation and subsequent fibrosis in human and in
      animal models. Alveolar epithelial type 2 cells (T2 cells) are known to play a
      crucial role in the repair process after BLM injury. We hypothesized that
      resistance of T2 cells to BLM-damage was associated with an increase in their
      antioxidant system activity. We developed an animal model of lung lesions
      preceding fibrosis, using daily intraperitoneal administration of BLM (1.5 mg/day
      over 7 and 14 days). We observed a body weight stabilization in BLM-treated rats
      from the third day. After 14 days of BLM treatment, the number of cells recovered
      by bronchoalveolar lavage was significantly increased (p < 0.05), with a dramatic
      increase (p < 0.01) in the percentage of neutrophils associated with a decrease
      in macrophage percentage (p < 0.01) No evidence of fibrosis was seen by
      microscopic studies at this time. However, T2 cells in 14-day-treated rats were
      swollen with enlarged lamellar inclusion bodies. Biochemical study of freshly
      isolated T2 cells displayed a significant decrease of lactate dehydrogenase (LDH)
      released by these cells when isolated from 14-day-treated rats as compared with 7
      day. By contrast, BLM induced an increase in superoxide dismutase (SOD) and
      glutathione peroxidase activities. Cell content of glutathione was decreased and
      gamma-glutamyl transpeptidase activity was markedly increased. These results show
      that BLM induces changes in the antioxidant system of T2 cells, particularly in
      the glutathione system.

PMID- 9538942
TI  - Cell-specific differences in the susceptibility of potential cellular targets of
      human origin derived from blood and lung following treatment with 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD).
AB  - The induction of cytochrome P4501A (CYP1A1) enzyme activity is one of the best
      studied direct effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related
      compounds and has been shown to be a sensitive biomarker of exposure to
      polycyclic aromatic hydrocarbons (PAH) in different experimental animal species
      as well as in humans. TCDD has also been shown to modulate cytokine gene
      expression in human keratinocytes, including IL-1 beta, TGF-alpha and TFG-beta 2.
      In the present studies, the aim was to determine whether different cellular
      targets of human origin differed in susceptibility to TCDD as measured by CYP1A1
      activity and mRNA expression, and whether cytokine gene induction/suppression
      correlated with TCDD susceptibility. Human airway epithelial cells, alveolar
      macrophages (AM), peripheral blood monocytes and lymphocytes (PBL) were exposed
      to 10(-10)-10(-7) mol/L TCDD. CYP1A1 enzyme activity was determined by
      ethoxyresorufin-O-deethylase (EROD) activity, mRNA expression of CYP1A1 was
      measured by semiquantitative PCR assay. The secretion and/or gene expression of
      specific cytokines, including IL-6, IL-8, and IL-1 beta were also examined.
      Overall, there was a clear correlation between TCDD-induced enzyme activity and
      CYP1A1 mRNA levels, which were dose-dependently increased in the
      bronchoepithelial cells and PBL. The human airway epithelial cells (BEAS-S6 cell
      line and primary cells) appeared to be the most inducible cellular target, with
      up to 50-fold increases at 10(-8) mol/L TCDD with an EC50 of 3 x 10(-11) mol/L
      TCDD. The pokeweed mitogen-activated peripheral blood lymphocytes revealed
      approximately 5-fold less capacity in CYP1A1 activity, with high interindividual
      variabilities (EC50 3 x 10(-9) mol/L TCDD). In contrast, CYP1A1 enzyme activity
      in both AM and purified peripheral blood monocytes, which were costimulated with
      LPS and/or GM-CSF, could not be detected. CYP1A1 mRNA levels, however, were
      detectable and only marginally enhanced in response to TCDD. The ability of all
      these cells to express and produce the proinflammatory cytokines IL-6 and IL-8
      was neither enhanced nor impaired by TCDD. These results indicate that cell types
      found in human lung and peripheral blood vary in susceptibility to TCDD, with the
      lung epithelium being highly susceptible and the alveolar macrophage being
      nonsusceptible. However, expression and production of specific cytokines such as
      IL-6 and IL-8, which may potentiate inflammatory processes and/or work as
      mitogens, does not appear to be influenced by TCDD.

PMID- 9538943
TI  - Hsp72 mRNA production in cultured human cells submitted to nonlethal aggression
      by heat, ethanol, or propanol. Application to the detection of low concentrations
      of chromium(VI) (potassium dichromate).
AB  - The HT29 and HepG2 human cell lines have been shown to express stress proteins
      (heat shock proteins, HSP) when submitted to a variety of sublethal environmental
      aggressions. In the present study, these cells were submitted to standardized
      mild aggression by heat, ethanol, or propan-1-ol in vitro. Subsequent formation
      of the hsp72 mRNA was measured by a very specific RNase protection method using a
      radiolabeled antisense RNA probe. The accumulation of the mRNA coding for the
      HSP72 stress proteins was found to be maximum within 3 h after the aggression.
      Results were obtained faster and were much more interpretable than those from the
      classical method involving the autoradiography of electrophoretically separated
      35S-labeled proteins, especially in the case of very weak, threshold-level,
      aggressions. When this model was used as a biological system for the detection of
      low concentrations of chromium(VI) (Cr2O7(2-)), it was possible to detect
      concentrations as low as 0.5 mumol/L. This indicates that measuring indices of
      stress induction in human cultured cells can be several orders of magnitude more
      sensitive than the commercial Microtox assay used for detecting low levels of
      pollution.

PMID- 9538944
TI  - Carbon monoxide induces murine thymocyte apoptosis by a free radical-mediated
      mechanism.
AB  - Carbon monoxide (CO) induces acute or chronic toxicity, according to the level
      and duration of the exposure. Since chronic CO exposure was shown to have
      immunosuppressive effects (as it decreases the frequency of rat splenic
      immunocompetent cells and immunoglobulin production), we investigated the effect
      of CO on thymocytes, since these are the most sensitive cells to oxidative damage
      from the lymphoid lineage. We exposed thymocytes to CO, then determined their
      apoptotic index after 6 h of incubation at 37 degrees C using the fluorochrome
      Hoechst 33342 and electron microscopy and found an increase of apoptosis in CO
      exposed thymocytes. Trolox (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic
      acid), an antioxidant vitamin E analog, decreased CO-induced thymocyte apoptosis
      unlike methylene blue, L-nitroarginine methyl ester or pyrrolidine
      dithiocarbamate. We also observed that lipid peroxidation was increased in the CO
      exposed thymocytes and that it was inhibited by Trolox. Our results suggest that
      CO induces thymocyte apoptosis by a free radical-mediated mechanism which can be
      inhibited by Trolox but which does not involve the activation of the guanylyl
      cyclase-cGMP pathway.

PMID- 9538945
TI  - Cellular characteristics of epithelial cell lines from juvenile rat liver:
      selective induction of glutamine synthetase by dexamethasone.
AB  - Four epithelial cell lines established from juvenile rat liver and selected on
      the basis of their capacity to prolong the lifespan of cocultured hepatocytes
      were compared with respect to several immunocytochemical markers (vimentin,
      cytokeratin 19, MAB 19C6), enzyme activities, and amino acid uptake systems.
      Their phenotypes were found to be quite different from that of hepatocytes and
      bile duct epithelial cells (BEC), but very similar among each other. In
      particular, a variety of functions affected by dexamethasone (DEX) or changing
      spontaneously in cultured hepatocytes and/or BEC, showed neither inducibility nor
      spontaneous changes in the four cell lines. Instead, the lines were inducible for
      glutamine synthetase (GS) by DEX, in contrast to hepatocytes and BEC but also to
      other juvenile or adult epithelial lines that did not support cocultured
      hepatocytes. In addition, they showed relatively high basal levels of GS
      activity, exceeding those found in adult epithelial cell lines and approaching
      the average values found for liver tissue. Basal as well as DEX-induced GS
      activity was reduced in the presence of newborn calf serum, while only DEX
      induced but not basal activity was suppressed by glutamine. These results suggest
      an origin of these four juvenile epithelial cell lines different from that of
      hepatocytes as well as of BEC. Furthermore, they suggest the coherent acquisition
      of new functional properties during early phases of cultivation of these cell
      lines; the selective inducibility of GS by DEX and its suppression by glutamine
      are the most intriguing of these, because neither is found in any normal cell
      type present in rat liver.

PMID- 9538946
TI  - Conditioned medium from cultured rat hepatocytes completely blocks induction of
      glutamine synthetase by dexamethasone in several rat liver epithelial cell lines.
AB  - A variant RL-ET-1G of a rat liver epithelial cell line (RL-ET-1) characterized by
      a very high inducibility for glutamine synthetase (GS) in response to
      dexamethasone was established by cultivation in glutamine-free, glutamate
      supplemented culture medium. Using this cell line, conditioned medium produced by
      periportal hepatocytes in primary culture was found to suppress this induction,
      acting with a lag-phase of about 8 h irrespective whether the GS activity was
      basal or preinduced. Analysis of the response of several epithelial cell lines to
      the conditioned medium showed a reciprocal relationship between the dexamethasone
      dependent induction and the residual activity after exposure to the conditioned
      medium, indicating that a hypothetical factor in the conditioned medium was
      interfering with the induction process but not with the basal GS level of these
      cells. Careful analysis revealed that the effect of the conditioned medium was
      neither due to deficiency of a component used up by the hepatocytes, nor due to
      glutamine or ammonia, both of which affected GS activity at concentrations above
      0.5 mmol/L. The hypothetical factor was found to be quite small (molecular mass
      range 100-500 Da), heat and acid stable, as well as highly water soluble. Most
      interestingly, the conditioned medium did not suppress GS induction in astroglial
      cells and in the two hepatoma cell lines C2 and FAO, but strongly diminished the
      spontaneous induction of GS in cocultured pig hepatocytes, suggesting that the
      hypothetical factor acts primarily on normal nontransformed liver-derived cell
      populations.

PMID- 9538947
TI  - Cement injuries: Part II. Cement burns resulting in necrotic ulcers due to
      kneeling on wet cement.

PMID- 9538948
TI  - Pfiesteria piscicida.

PMID- 9538949
TI  - The artful use of topical steroids.

PMID- 9538951
TI  - Red scrotum syndrome.

PMID- 9538950
TI  - Congenital lower lip pits--a very rare syndrome? Report of two cases and review
      of the literature.
AB  - A 43-year-old white man and his 12-year-old daughter both displayed congenital
      lower lip pits. Since Van der Woude's description of this syndrome more than
      forty years ago, little attention has been given to this uncommon anomaly,
      probably due to variable expressivity, incomplete penetrance, and recognition of
      its clinical stigmata. We describe two family members with Van der Woude's
      syndrome and review its clinical aspects, differential diagnosis, and treatment.

PMID- 9538952
TI  - Basal cell carcinoma of the penis.

PMID- 9538953
TI  - Intradermal testing and sublingual desensitization for nickel.
AB  - Thirty-nine patients with nickel allergy as diagnosed by results of clinical
      history and intradermal testing with nickel sulfate were treated by sublingual
      hyposensitization. Intradermal testing was accurate and titration showed the
      degree of sensitivity. The immunologic principle of oral tolerance was used in
      treatment. Eighty-five percent of the thirty-nine patients showed subjective
      improvement in their dermatitis and all showed objective evidence of decreased
      intradermal sensitivity. None of the patients' conditions worsened. The use of
      oral treatment with nickel sulfate deserves broader clinical trial.

PMID- 9538955
TI  - Subcutaneous pheohyphomycotic cyst from a traumatic injury: reactivation after
      thirty-five years.
AB  - Pheohyphomycoses are an uncommon diverse group of dematiaceous fungi present in
      soil and plant material and are potential pathogens. We report the case of a 45
      year-old white Hispanic woman who presented with a hard round cyst on the dorsum
      of her right foot caused by a traumatic implantation of a piece of wood thirty
      five years earlier. The cyst was surgically excised and the patient empirically
      treated with a two-month course of oral itraconazole. To our knowledge, this
      represents a case of the longest-lived asymptomatic pheohyphomycotic cyst in an
      immunocompetent person ever reported. The clinical manifestations, treatment
      options, and disease course are reviewed.

PMID- 9538954
TI  - Kaposi's sarcoma following long-term immunosuppressive therapy: clinical,
      histologic, and ultrastructural study.
AB  - Multifocal Kaposi's sarcoma in a patient with chronic myeloid leukemia treated
      with busulfan, a cytostatic and suppressive drug, is reviewed. After five years
      of treatment, during which temporary remissions occurred, the patient experienced
      a relapse of leukemia and a considerable immune deficiency. This was expressed by
      a decrease in the ratio of CD4/CD8 lymphocytes in the peripheral blood. The
      relation of Kaposi's sarcoma with leukemia, as well as with the state of immunity
      in this case, does not evoke any doubts. Verification of oncologic treatment
      brought about a remission of leukemia, an improvement in the patient's immune
      state, as well as an inhibition of new foci of the Kaposi's sarcoma in the skin
      in the course of a few months of follow-up evaluation.

PMID- 9538956
TI  - Testicular cancer presenting as urticaria.

PMID- 9538957
TI  - Long-term remission of two feet-one hand syndrome.
AB  - Two feet-one hand syndrome is also defined as bilateral plantar tinea pedis with
      coexistent unilateral tinea manuum. Toenails and fingernails may also be affected
      and the dermatophyte Trichophyton rubrum is the usual cause. When there is nail
      involvement, especially of the toenails, treatment with an oral antifungal agent
      should be considered because topical therapy alone is usually not effective.
      However, relapses are common. With the advent of new, more effective antifungal
      drugs such as itraconazole, terbinafine, and fluconazole, it is hoped that this
      troublesome and recalcitrant disorder may be better controlled.

PMID- 9538958
TI  - Molluscum contagiosum in a soft fibroma: a particular combined lesion.
AB  - A case of a single molluscum contagiosum occurring on the surface of a
      preexisting soft fibroma in an adult patient is reported. The most common
      clinical form of this viral lesion is multiple grouping papules with a central
      umbilication and its histologic feature is characteristic. Previous cases of
      mollusca combining with other lesions have been rarely described. Our lesion was
      probably due to its localization on the soft fibroma, whose exophytic growing
      represented a favoring factor for trauma and the consequent occurrence of the
      viral disease.

PMID- 9538959
TI  - Cellulitis caused by Citrobacter diversus in a patient with multiple myeloma.
AB  - The most common cause of cellulitis is streptococci. Coagulase-negative
      staphylococci and gram-negative bacteria, such as Serratia spp., Proteus spp.,
      and other Enterobacteriaceae may produce cellulitis in the immunocompromised
      patient. We report a case of Citrobacter diversus-induced cellulitis, resembling
      streptococcal infection, in a patient with multiple myeloma.

PMID- 9538960
TI  - Localized cutaneous Nocardia brasiliensis mimicking foreign body granuloma.
AB  - Nocardia brasiliensis is recognized in the United States as an infectious agent
      of the skin that may present as an abscess, ulcer, or granuloma with or without
      "sporotrichoid" spread, and rarely causes systemic disease. Treatment with
      trimethoprim/sulfamethoxazole is usually curative. We present a patient with
      multiple erythematous, painful, draining nodules that developed thirty-six months
      after trauma and subsequent contamination with soil in Bermuda. A foreign body
      granuloma was suspected clinically, and excision was performed followed by
      recurrence of the lesions. Histologic examination and culture were consistent
      with nocardiosis. Differential diagnosis of foreign body granulomas also should
      include infection with N. brasiliensis even after a long incubation period.
      Culture and drug susceptibility testing of affected tissue should be performed
      for diagnosis and management.

PMID- 9538961
TI  - Diabetes and peripheral neuropathy.

PMID- 9538962
TI  - The effect of short periods of caloric restriction on weight loss and glycemic
      control in type 2 diabetes.
AB  - OBJECTIVE: To determine whether an intermittent very-low-calorie diet (VLCD)
      improves weight loss and glycemic control more than moderate caloric restriction
      alone. RESEARCH DESIGN AND METHODS: Individuals with type 2 diabetes (n = 54) who
      were > or = 20% over ideal body weight participated in a 20-week behavioral
      weight control program. Subjects were randomized to either a standard behavioral
      therapy (SBT) group or to one of two VLCD groups. SBT subjects received a 1,500
      1,800 kcal/day diet throughout. Both VLCD groups followed a VLCD for 5
      consecutive days during week 2, followed by either intermittent VLCD therapy for
      1 day/week for 15 weeks (1-day) or for 5 consecutive days every 5 weeks (5-day),
      with a 1,500-1,800 kcal/day diet at other times. RESULTS: Both VLCD groups lost
      more weight than the SBT group over the 20 weeks (P = 0.04). Although the groups
      did not differ in fasting plasma glucose (FPG) changes at 20 weeks, more subjects
      in the 5-day group attained a normal HbA1c when compared with the SBT group (P =
      0.04). This benefit was independent of the effects of weight loss. The best
      predictor of overall change in FPG and HbA1c was the FPG response during the
      first 3 weeks of the program. CONCLUSIONS: Periodic VLCDs improved weight loss in
      diabetic subjects. A regimen with intermittent 5-day VLCD therapy seemed
      particularly promising, because more subjects in this group attained a normal
      HbA1c. Moreover, the glucose response to a 3-week period of diet therapy
      predicted glycemic response at 20 weeks, and it was a better predictor of the 20
      week response than initial or overall weight loss.

PMID- 9538963
TI  - Effects of a monounsaturated fatty acid-enriched hypocaloric diet on
      cardiovascular risk factors in obese patients with type 2 diabetes.
AB  - OBJECTIVE: To determine whether the lipoprotein response to weight loss in obese
      patients with type 2 diabetes can be improved by modifying the macronutrient
      composition of the commonly prescribed low-fat, high-carbohydrate (CHO)
      hypocaloric diet. RESEARCH DESIGN AND METHODS: Nine obese patients with type 2
      diabetes were treated with a monounsaturated fatty acid (MUFA)-enriched weight
      reducing formula diet and compared with eight obese patients with type 2 diabetes
      treated with a low-fat, high-CHO weight-reducing formula diet. Weight loss ensued
      for 6 weeks, followed by 4 weeks of refeeding using isocaloric formulas enriched
      with MUFA or CHO, respectively. Fasting blood samples were obtained to measure
      plasma lipoproteins and LDL susceptibility to oxidation (measured as lag time:
      time required to induce in vitro formation of conjugated dienes). RESULTS: At
      baseline, there were no differences between the groups in plasma lipids,
      lipoproteins, or LDL susceptibility to oxidation. Weight loss was similar between
      the groups. Dieting resulted in decreases in total plasma cholesterol, LDL, HDL,
      triglycerides, and apolipoproteins A and B (P < 0.05), but the MUFA group
      manifested a greater decrease in total cholesterol, triglycerides, and
      apolipoprotein B and a smaller decrease in HDL and apolipoprotein A than the CHO
      group (P < 0.05). Improvements in these parameters were sustained during
      refeeding. After dieting, lag time was prolonged in the MUFA group (208 +/- 10
      min) compared with the CHO group (146 +/- 11 min; P < 0.05). Lag time was
      prolonged further during refeeding in the MUFA group (221 +/- 13 min, P = 0.10),
      while the CHO group remained unchanged (152 +/- 9 min, P < 0.05). Lag time
      correlated strongly with the oleic acid content of LDL after dieting and
      refeeding (r = 0.74 and r = 0.93, respectively; both P < 0.001). CONCLUSIONS:
      Macronutrient content is an important determinant of the lipoprotein response to
      weight loss in obese patients with type 2 diabetes. MUFA-enriched hypocaloric
      diets potentiate the beneficial effects of weight loss to ameliorate
      cardiovascular risk factors in obese patients with type 2 diabetes.

PMID- 9538964
TI  - Stimulation of insulin secretion by fructose ingested with protein in people with
      untreated type 2 diabetes.
AB  - OBJECTIVE: Ingested protein provides substrate for gluconeogenesis and strongly
      stimulates insulin and glucagon secretion, but it has little effect on the
      glucose concentration in people with type 2 diabetes. Ingested fructose also is a
      substrate for gluconeogenesis, modestly stimulates insulin and glucagon
      secretion, and has little effect on the plasma glucose. Therefore we were
      interested in determining if ingestion of fructose along with protein would
      result in an additive, greater than additive, or less than additive effect on
      circulating insulin, glucagon, and glucose concentrations. RESEARCH DESIGN AND
      METHODS: Seven male subjects with untreated type 2 diabetes were fasted overnight
      and then were given either 25 g fructose, 25 g protein, 25 g fructose plus 25 g
      protein, or water only at 0800. Subjects also ingested 50 g glucose on two
      separate occasions. Plasma glucose, insulin, C-peptide, glucagon, alpha-amino
      nitrogen, urea nitrogen, nonesterified fatty acids, and triglyceride
      concentrations were determined over the subsequent 5 h. RESULTS: The glucose
      concentration was only modestly increased and the area responses were similar
      when protein, fructose, or the combination was ingested. Thus, the glucose
      response to the combination was less than additive. The insulin area response to
      protein was 2.5-fold greater than to fructose, and the response to the two
      nutrients was additive and quantitatively similar to the response to 50 g
      glucose. The glucagon area response was less than additive, i.e., there was an
      interaction between the protein and fructose that resulted in a smaller than
      expected response. CONCLUSIONS: When protein and fructose were ingested together,
      the insulin response was similar to that following ingestion of 50 g glucose. It
      also was as expected based on the response to the individual nutrients. In
      contrast, the glucose and glucagon responses were significantly less than
      expected. These data may be useful in dietary planning for subjects with type 2
      diabetes.

PMID- 9538965
TI  - Evaluation of a self-administered sensory testing tool to identify patients at
      risk of diabetes-related foot problems.
AB  - OBJECTIVE: To study the use of a self-administered sensory testing tool designed
      to identify individuals at risk for diabetes-related foot problems and determine
      the inter-rater reliability between patient and provider sensory evaluations.
      RESEARCH DESIGN AND METHODS: Nine centers in eight states with established foot
      prevention centers mailed 196 self-screening testing materials to randomly
      selected patients with diabetes scheduled for follow-up appointments. Patients
      were instructed to perform a sensory test using a 10-g nylon filament at
      specified sites on the foot and to complete a brief survey form before their
      appointment. During the follow-up appointment, providers retested patients using
      an identical sensory filament at the same sites and completed a provider survey.
      RESULTS: Of the patients, 145 kept their appointments and completed the self
      screening materials. There were 141 patient and 137 provider surveys that
      indicated the instructions were clear and easy to use. Sixty-eight percent of the
      patients reported self-testing without the assistance of another person. Patient
      and provider sensory test findings disagreed (P = 0.0014) in 18 of 145 cases and
      fair inter-rater reliability was found (kappa = 0.73). Disagreement in sensory
      tests was related to patient age (P = 0.012). Sensory loss, previously undetected
      by providers, was found in 23 case subjects. CONCLUSIONS: Self-administered
      sensory tests provide patients an opportunity to share in the responsibility for
      preventing diabetes-related foot problems but should not replace routine foot
      evaluation by a provider.

PMID- 9538966
TI  - Optimal time of administration of insulin lispro. Importance of meal composition.
AB  - OBJECTIVE: To compare the glucodynamics of pre- and postprandial administration
      of insulin lispro using test meals of differing composition. RESEARCH DESIGN AND
      METHODS: Twenty subjects with IDDM were studied on four separate occasions. Ten
      subjects ingested high-carbohydrate and high-fat breakfasts with a large liquid
      component, and 10 subjects ingested high-carbohydrate and high-fat breakfasts in
      a more solid form. With each meal, insulin lispro was injected 10 min preprandial
      on one occasion and 20 min postprandial on another. The magnitude and temporal
      pattern of postprandial glucose excursions were observed. RESULTS: With all meal
      types studied, postprandial blood glucose excursions were significantly smaller
      when insulin lispro was administered preprandially (P < 0.05). With both high
      carbohydrate meals and the liquid high-fat meal, preprandial administration of
      lispro was associated with modest postprandial increments of blood glucose. With
      the solid high-fat meal, preprandial lispro produced a cumulative decline in
      postprandial blood glucose, whereas blood glucose rose when lispro was
      administered postprandially. CONCLUSIONS: For meals with a high carbohydrate
      content, the optimal time of administration of lispro is preprandial. However,
      for meals with a high solid fat content, postprandial administration of lispro
      may be preferable.

PMID- 9538967
TI  - The effect of the insulin analog lispro on nighttime blood glucose control in
      type 1 diabetic patients.
AB  - OBJECTIVE: Unmodified regular insulin has a long absorption tail, unlike the fast
      acting insulin analog lispro, and may contribute to hypoglycemia in the early
      part of the night. A randomized crossover double-blind study was performed to
      compare blood glucose concentrations in the early part of the night in type 1
      diabetic patients receiving lispro or unmodified regular human insulin, in random
      order, on 2 separate study days. RESEARCH DESIGN AND METHODS: We studied 23 C
      peptide-negative patients; 12 were using a premeal plus basal insulin regimen,
      and 11 were using twice-daily insulin injections. Patients were admitted to the
      investigation unit at 5:00 P.M. and received a single dose of lispro or
      unmodified regular human insulin before the evening meal. In both groups, the NPH
      insulin dose remained unchanged. Identical meals and snacks were eaten at the
      same time during both study days. RESULTS: Average postprandial (6:00-10:00 P.M.)
      blood glucose concentrations were significantly lower after lispro therapy
      compared with human insulin (7.1 +/- 0.4 [SE] vs. 8.5 +/- 0.4 mmol/l, P =
      0.0002). Nighttime (midnight to 4:00 A.M.) blood glucose concentrations were
      significantly higher after lispro compared with human insulin (10.3 +/- 0.4 vs.
      9.1 +/- 0.4 mmol/l, P = 0.02). This difference was greatest in patients on the
      premeal plus basal insulin regimen (11.6 +/- 0.5 vs. 8.7 +/- 0.4 mmol/l, P <
      0.001). The incidence of nocturnal hypoglycemia (midnight to 4:00 A.M., blood
      glucose < 3.5 mmol/l) was less with lispro compared with unmodified insulin (1
      vs. 6 patients, P = 0.04). Nighttime (midnight to 4:00 A.M.) 3-hydroxybutyrate
      (102 +/- 13 vs. 51 +/- 7 mumol/l, P = 0.000) and glycerol (52 +/- 3 vs. 42 +/- 2
      mumol/l, P < 0.01) were significantly higher after lispro therapy compared with
      human insulin in patients on the premeal plus bolus insulin regimen. CONCLUSIONS:
      Lispro can improve postprandial blood glucose control and reduce the incidence of
      nocturnal hypoglycemia at the expense of nocturnal hyperglycemia and
      hyperketonemia in patients using a premeal plus basal insulin regimen.

PMID- 9538968
TI  - Long-term follow-up of diabetes in two patients with thiamine-responsive
      megaloblastic anemia syndrome.
AB  - OBJECTIVE: To describe a 15-year follow-up of diabetes and to present data
      regarding pancreatic beta-cell function in two adolescents affected by the
      thiamine-responsive megaloblastic anemia (TRMA) syndrome. CASE REPORTS: The first
      patient (PMR) is a 17.5-year-old Italian girl who presented megaloblastic anemia
      at 7.5 months of age. At age 2.5 years, because of the presence of diabetes and
      sensorineural deafness, she was diagnosed with TRMA syndrome and started
      treatment with thiamine-HCl, followed very early by benzoyloxymethyl-thiamine
      (BOM-T). The second patient (PF) is a 16.8-year-old Italian boy born to
      consanguineous parents. Sensorineural deafness was diagnosed at age 1.5 years,
      while diabetes with ketoacidosis and megaloblastic anemia were diagnosed at age 3
      years. Treatment with thiamine HCl was started immediately after diagnosis and
      changed to BOM-T 2 months later. Subsequent to the initiation of the vitamin, the
      two patients did not require insulin for approximately 7 and 10 years,
      respectively. Puberty was determinant in deteriorating the metabolic control in
      these patients, leading to treatment with an oral hypoglycemic agent and finally
      to a reinstitution of insulin therapy. CONCLUSIONS: The hormonal assessment in
      our patients (normal insulin response to oral glucose in childhood, preserved C
      peptide secretion in case 2) and the good response to an oral hypoglycemic agent
      would indicate that the pancreatic disease may initiate as type 2 diabetes and
      may progress after several years to an insulin-requiring diabetes, as indicated
      by the exhaustion of the insulin secretory capacity.

PMID- 9538969
TI  - The epidemiology and cost of inpatient care for peripheral vascular disease,
      infection, neuropathy, and ulceration in diabetes.
AB  - OBJECTIVE: To describe the epidemiology and costs of the acute care of peripheral
      vascular disease, infection, neuropathy, and ulceration in a U.K. population with
      special consideration of those patients with diabetes. RESEARCH DESIGN AND
      METHODS: Routine data describing inpatient care for a 4-year period were analyzed
      (financial years 1991/1992 to 1994/1995). These data had undergone record-linkage
      to draw together records from the same patients, and records of patients with
      diabetes were flagged. Cost estimates were determined by attributing a diagnosis
      related group cost-weight to each record. RESULTS: A total of 4,245 admissions
      (1.2% of all admissions) had a primary diagnosis of peripheral vascular disease,
      infection, neuropathy, or ulceration, and 7,379 (2.1%) admissions had these
      categories recorded in any one of six diagnostic fields. These figures were
      generated by 3,159 and 4,751 patients, respectively. This represented a range of
      crude annual incidence of admission of between 1.9 and 2.9 per 1,000 people.
      Patients with diabetes accounted for 625 (15.4%) of primary admissions, a crude
      annual incidence of admission of 18.8 per 1,000. The age-standardized relative
      risk of admission for patients with diabetes to the nondiabetic population was
      7.61 for men and 6.85 for women. The length of stay for patients with diabetes
      was almost twice that of the nondiabetic population (15.5 vs. 8.7 days). The
      relative risk of hospital mortality (diabetes vs. non-diabetes) was 2.83.
      Surgical procedures were carried out on 857 patients, 272 (31.2%) with diabetes.
      This represented an age-standardized relative risk of 31.19. The estimated cost
      of admissions for primary diagnoses in these categories over 4 years was
      6,128,211 pounds ($9,743,855). Patients with diabetes accounted for 1,236,623
      pounds ($1,966,230), an excess of 87% attributable to the diabetic state.
      CONCLUSIONS: Diabetes is confirmed as a significant risk factor for peripheral
      vascular disease, infection, neuropathy, and ulceration. The severity of these
      disorders in terms of increased risk of hospital mortality, length of stay, and
      risk of surgical procedure is also demonstrated for those patients with diabetes.

PMID- 9538970
TI  - Comparison of GAD and ICA512/IA-2 antibodies at and after the onset of IDDM.
AB  - OBJECTIVE: Longitudinal changes in GAD antibody (Ab) and ICA512/IA-2 (ICA512) Ab
      were examined in relation to age at the onset of diabetes and autoimmunity
      against the thyroid gland. RESEARCH DESIGN AND METHODS: GADAb, ICA512Ab, and
      antithyroid autoantibody were examined at onset in 40 juvenile-onset IDDM
      patients (17 males, 23 females, age at onset 9.4 +/- 4.1 years, range 1.7-20). To
      assess the changes in antibody levels, 29 patients were followed up with
      sequential serum samples for up to 5 years. RESULTS: At onset, GADAb, ICA512Ab,
      and antithyroid autoantibody (thyroglobulinAb or thyroid peroxidaseAb) were found
      in 70, 58, and 25% of the 40 patients, respectively. Prepubertal patients (n =
      21) had a significantly higher prevalence and index of ICA512Ab compared with
      pubertal patients (n = 19) (76 vs. 37%, P = 0.012, and 2.43 +/- 2.36 vs. 0.66 +/-
      1.23, P = 0.011), while GADAb was more prevalent in pubertal patients (57 vs.
      84%, P = 0.09). A longitudinal analysis of GADAb and ICA512Ab showed that GADAb
      levels declined more slowly than those of ICA512Ab (P = 0.008). Patients with
      continuous extremely high levels of GADAb also had high levels of antithyroid
      autoantibody. CONCLUSIONS: The measurement of ICA512Ab is useful in prepubertal
      patients, who often show rapid progression of the disease. The presence of
      autoimmunity against thyroid gland seems to influence the GADAb level but not the
      ICA512Ab level.

PMID- 9538971
TI  - Incidence and progression of diabetic retinopathy in Hispanics and non-Hispanic
      whites with type 2 diabetes. San Luis Valley Diabetes Study, Colorado.
AB  - OBJECTIVE: To learn if Hispanic people with type 2 diabetes have excess incidence
      and/or progression of diabetic retinopathy and to explore the association of risk
      factors with diabetic retinopathy. RESEARCH DESIGN AND METHODS: There were 244
      subjects with type 2 diabetes (65.3% Hispanic) with at least one follow-up visit
      between 1984 and 1992 examined for the development of retinopathy over a median
      of 4.8 years (range 2.0-6.6 years). Stereo fundus photos were graded by the
      University of Wisconsin Reading Center. RESULTS: Of the 169 subjects without
      retinopathy at baseline, 47 developed some retinopathy, an incidence rate of 63.7
      per 1,000 person-years (PY), or a 4-year cumulative incidence of 22.5%. The
      Hispanic incidence rate was 58.3/1,000 PY (95% CI: 39.4-83.3), which was lower
      than among non-Hispanic whites, 76.1/1,000 PY (44.3-121.9). Progression occurred
      in 24 of the 75 subjects with retinopathy at baseline, a 4-year cumulative rate
      of 24.1%. Logistic regression showed that insulin treatment was associated with
      higher risk of any retinopathy (odds ratio [OR] = 8.45, 2.65-26.97), and both
      systolic blood pressure (odds ratio [OR] = 1.58, 0.99-2.52) and total GHb (OR =
      1.46, 0.99-2.17) nearly attained statistical significance. After adjustment for
      multiple potential risk factors, the Hispanic/non-Hispanic white OR was 0.66
      (0.28-1.57). CONCLUSIONS: No excess risk for incident retinopathy was found among
      Hispanic compared with non-Hispanic white subjects in this population. These
      results are consistent with our previously reported prevalence data from the same
      population but differ from reports of excess prevalence among Texas Hispanics. No
      other Hispanic incidence data are available to assist in reconciling this
      difference.

PMID- 9538972
TI  - Impact of diabetes on mortality after the first myocardial infarction. The
      FINMONICA Myocardial Infarction Register Study Group.
AB  - OBJECTIVE: To study diabetic and nondiabetic patients with their first myocardial
      infarction to determine overall 1-year mortality, out-of-hospital mortality, 28
      day mortality of hospitalized patients, and 1-year mortality of 28-day survivors.
      RESEARCH DESIGN AND METHODS: This study--based on the FINMONICA Myocardial
      Infarction Register, a part of the Finnish contribution to the WHO MONICA Project
      (World Health Organization Multinational Monitoring of Trends and Determinants of
      Cardiovascular Disease)--covered coronary heart disease (CHD) deaths and acute
      CHD events occurring during hospitalization among residents of Finland aged 25-64
      years in three geographically defined areas. The study population comprised 620
      diabetic and 3,445 nondiabetic patients who had their first myocardial infarction
      during the years 1988-1992. RESULTS: The age- and area-adjusted mortality rates
      and hazard ratios (HRs) for diabetic versus nondiabetic patients (95% CI) were as
      follows: The 1-year mortality rate was 44.2% in diabetic men and 32.6% in
      nondiabetic men (HR, 1.38; 1.18-1.61) and 36.9% in diabetic women and 20.2% in
      nondiabetic women (HR, 1.86; 1.40-2.46); the out-of-hospital mortality rate was
      28.3% in diabetic men and 22.4% in nondiabetic men (HR, 1.25; 1.03-1.52) and
      10.4% in diabetic women and 11.0% in nondiabetic women (HR, 0.95; 0.58-1.54); the
      28-day mortality rate of hospitalized patients was 14.4% in diabetic men and 8.8%
      in nondiabetic men (HR, 1.58; 1.15-2.18) and 21.7% in diabetic women and 7.8% in
      nondiabetic women (HR, 2.60; 1.71-3.95); and the 1-year mortality rate of 28-day
      survivors was 9.6% in diabetic men and 5.0% in nondiabetic men (HR, 1.97; 1.25
      3.12) and 10.7% in diabetic women and 2.5% in nondiabetic women (HR, 4.17; 2.05
      8.51). CONCLUSIONS: The high mortality rate of diabetic patients after their
      first myocardial infarction and the high proportion of out-of-hospital deaths in
      this group imply that vigorous primary and secondary preventive measures should
      become an integral part of their medical care.

PMID- 9538973
TI  - Study of genetic prediabetic south Indian subjects. Importance of
      hyperinsulinemia and beta-cell dysfunction.
AB  - OBJECTIVE: To study 1) whether abdominal adiposity was present in adult offspring
      of two NIDDM parents, 2) whether abdominal adiposity was associated with the
      development of glucose intolerance, and 3) the association of pancreatic beta
      cell function with impaired glucose tolerance (IGT) and NIDDM in these groups.
      RESEARCH DESIGN AND METHODS: One hundred offspring whose parents both had NIDDM
      were studied (60 men, 40 women, mean age 34 +/- 6.9 years, BMI 27.4 +/- 4.1
      kg/m2). None had a history of glucose intolerance. Nondiabetic control subjects
      with no family history of diabetes were also studied for comparison (21 men, 19
      women, age 36 +/- 10.3 years, BMI 26 +/- 3.7 kg/m2). A standard oral glucose
      tolerance test was done for all, and plasma glucose, C-peptide, and insulin
      responses were measured. Abdominal fat measurements at L4-L5 were made using a
      computed axial tomography scan. Subcutaneous fat (SF), visceral fat (VF), and
      total fat (TF) areas were measured and VF/SF ratio was calculated. An index of
      insulin secretion (delta I/G) was derived as the ratio of incremental insulin at
      30 min divided by 30-min plasma glucose. RESULTS: IGT was detected in 32
      offspring and diabetes in 21 offspring. Diabetic men had a higher TF area than
      the other groups. SF, VF, and VF/SF ratios were similar in control men and in
      offspring with normal glucose tolerance (NGT), IGT, or diabetes. Among control
      subjects, women had significantly lower VF than men. Female offspring had higher
      VF than the control subjects, but intragroup variations were absent. Fasting
      insulin and all C-peptide responses were higher in NGT compared with control
      subjects (P < 0.02). The 2-h insulin and C-peptide responses were higher in IGT
      subjects (P < 0.005). In diabetic subjects, the insulin-to-glucose ratio, C
      peptide-to-glucose ratio, and delta I/G were significantly low compared with all
      other groups (P < 0.005). Multiple logistic regression analysis showed that the
      area of insulin response had a positive association and delta I/G had a negative
      association with diabetes, while age, sex, BMI, waist-to-hip ratio, abdominal fat
      areas, fasting and 2-h insulin, area of insulin, and the C-peptide measurements
      did not show independent associations. Two-hour insulin showed a positive
      association with IGT, while increasing area of insulin showed a negative
      association. CONCLUSIONS: Visceral adiposity seemed to precede glucose
      intolerance only in women, but it had no independent association with IGT or
      NIDDM. Insulin resistance, indicated by higher plasma insulin response, and
      insulin secretory defect, indicated by low delta I/G at 30 min, were associated
      with diabetes. beta-cell defect was not independently associated with IGT.
      Increased abdominal visceral adiposity does not appear to be a prerequisite for
      development of IGT or diabetes in Asian Indians with a strong genetic
      predisposition for diabetes.

PMID- 9538974
TI  - Early presentation of type 2 diabetes in Mexican-American youth.
AB  - OBJECTIVE: To describe features of pediatric-onset type 2 diabetes in the
      Hispanic population. RESEARCH DESIGN AND METHODS: The medical records of 55
      Hispanic subjects with diabetes who were treated from 1990 to 1994 in a pediatric
      clinic serving lower income Mexican-Americans were reviewed to assess the
      frequency and clinical features of type 2 diabetes. Additionally, nondiabetic
      siblings of several patients underwent oral glucose tolerance testing, and a
      survey of six high schools in the same county was performed. RESULTS: Seventeen
      of 55 (31%) of the diabetic children and adolescents had type 2 diabetes. An
      additional 4 Hispanic children with type 2 diabetes treated in other clinics were
      also identified, yielding a total of 21 subjects who were used to describe the
      characteristics of childhood type 2 diabetes. At presentation, all were obese
      (mean BMI 32.9 +/- 6.2 kg/m2), 62% had no ketonuria, and fasting C-peptide levels
      were elevated (4.28 +/- 3.43 ng/ml). Diabetes was easily controlled with diet,
      sulfonylureas, or low-dose insulin. No autoantibodies were present in those
      tested, and family histories were positive for type 2 diabetes. Compliance was
      poor, and 3 subjects developed diabetic complications. Of the tested siblings, 2
      of 8 had impaired glucose tolerance and 5 of 8 had stimulated hyperinsulinemia,
      correlated with BMI (r = 0.80, P < 0.05). The school survey identified 28
      diabetic adolescents, 75% more than expected (P < 0.01). The Hispanic enrollment
      at each school was highly correlated with the number of diabetic students (r =
      0.87, P = 0.011). CONCLUSIONS: Genetic susceptibility to type 2 diabetes, when
      coupled with obesity, can produce type 2 diabetes in Mexican-American children.
      This diagnosis should be considered in young Hispanic patients, who might
      otherwise be assumed to have type 1 diabetes, and also when caring for overweight
      Hispanic youth with a family history of type 2 diabetes, in whom intervention may
      prevent or delay diabetes onset.

PMID- 9538975
TI  - UKPDS 28: a randomized trial of efficacy of early addition of metformin in
      sulfonylurea-treated type 2 diabetes. U.K. Prospective Diabetes Study Group.
AB  - OBJECTIVE: To assess the efficacy over 3 years of the addition of metformin to
      maximum sulfonylurea therapy in type 2 diabetes. RESEARCH DESIGN AND METHODS:
      This multicenter randomized open-controlled trial was conducted in outpatient
      diabetes clinics in 15 U.K. hospitals. A total of 591 subjects who had already
      been randomly allocated to sulfonylurea therapy were taking maximum doses with
      suboptimal glycemic control, i.e., raised fasting plasma glucose (FPG)
      concentrations of 6-15 mmol/l but no significant hyperglycemic symptoms. The main
      outcome measures included FPG, glycated hemoglobin, protocol-defined marked
      hyperglycemia, body weight, blood pressure, fasting plasma lipids, compliance,
      and hypoglycemia and other side effects. RESULTS: After the addition of
      metformin, FPG concentrations decreased by mean (95% CI) -0.47 (-0.82 to -0.13)
      mmol/l over 3 years compared with an increase of 0.44 (0.07-0.81) mmol/l in
      subjects on sulfonylurea alone (P < 0.00001). Median FPG concentrations at 3
      years were 8.6 vs. 9.9 mmol/l, respectively (P < 0.00001), and HbA1c values were
      7.5 and 8.1%, respectively (P = 0.006). Adjustment for baseline BMI or FPG
      concentration did not affect response to therapy. Only 7% of those allocated to
      sulfonylurea plus metformin developed protocol-defined marked hyperglycemia
      compared with 36% of those allocated to sulfonylurea alone (P < 0.0001). Fasting
      plasma lipids, body weight, and blood pressure did not change significantly. The
      incidence of hypoglycemic episodes did not differ between groups: 4% on
      sulfonylurea plus metformin and 2% on sulfonylurea alone (NS). CONCLUSIONS: Early
      addition of metformin improved glycemic control in patients with suboptimal
      glycemic control while taking maximum sulfonylurea therapy, irrespective of
      obesity or baseline FPG concentrations.

PMID- 9538977
TI  - Clinical evaluation of a test for immediate and quantitative determination of
      urinary albumin-to-creatinine ratio. A brief report.

PMID- 9538976
TI  - Counterregulatory hormone responses after long-term continuous subcutaneous
      insulin infusion with lispro insulin.
AB  - OBJECTIVE: To determine whether the long-term use of insulin lispro (LP) affects
      the counterregulatory hormone response to hypoglycemia. RESEARCH DESIGN AND
      METHODS: Ten patients (age range 26-51 years; ratio of men to women 9:1; BMI 24.9
      +/- 0.48; mean HbA1c 7.84 +/- 0.25%) with IDDM, treated with continuous
      subcutaneous insulin infusion (CSII; Disetronic H-TRON V100) were studied using a
      double-blind, crossover design. Patients were randomized to LP or human regular
      insulin (HR) for 3 months and then crossed over to the other insulin for an
      additional 3 months. All meal boluses were given 0-5 min before breakfast, lunch,
      and dinner. Counterregulatory hormone responses to a stepped hypoglycemic clamp
      (consecutive glucose levels in mmol/l: 4.2; 3.5; 2.8, each for 1 h) were
      evaluated at the end of each treatment period. RESULTS: HbA1c was significantly
      lower with LP versus HR (7.47 +/- 0.28% vs. 7.9 +/- 0.26%, P = 0.04). The
      incidence of hypoglycemia per 30 days (capillary blood glucose < 3.0 mmol/l
      and/or symptoms) during the last month of the study was significantly lower with
      LP versus HR (8.7 +/- 2.9 vs. 11.8 +/- 2.9, P = 0.03). The total daily insulin
      dosage was not different in the two treatment periods. There was no episode of
      severe hypoglycemia or diabetic ketoacidosis. The peak growth hormone, cortisol,
      glucagon, and epinephrine responses during the same period of hypoglycemia were
      not different for each treatment period. CONCLUSIONS: The use of LP in CSII
      results in improved glycemic control and a decrease in the frequency of
      hypoglycemia without adversely affecting counterregulatory hormone response to
      hypoglycemia.

PMID- 9538978
TI  - Carotid artery stiffness is increased in microalbuminuric IDDM patients.
AB  - OBJECTIVE: In IDDM, the development of microalbuminuria, which is associated with
      an elevation in blood pressure within the normal range, is a risk factor for
      future cardiovascular disease. Vascular stiffness might be one of the factors
      involved because it increases systolic blood pressure and the workload of the
      heart. RESEARCH DESIGN AND METHODS: We investigated carotid artery stiffness with
      a noninvasive ultrasound method in 24 microalbuminuric and 53 normoalbuminuric
      IDDM patients and in 54 healthy control subjects. RESULTS: The distensibility
      coefficient, a measure of intrinsic vascular wall elasticity, was decreased in
      microalbuminuric IDDM (21.6 x 10(-3)/kPa) as compared with normoalbuminuric IDDM
      (24.8 x 10(-3)/kPa) and control subjects (25.9 x 10(-3)/kPa; P = 0.02). This
      result was based on a higher blood pressure in microalbuminuric patients. After
      correction for the difference in blood pressure, the distensibility coefficients
      were similar in the three groups. In the two diabetic patient groups taken
      together, age, blood pressure, female sex, diabetes duration, and cigarette
      smoking were determinants of a decreased distensibility. CONCLUSIONS: Blood
      pressure is a major determinant of increased arterial stiffness in
      microalbuminuric IDDM patients. Increased arterial stiffness may contribute to
      the accelerated progression of complications if concomitant hypertension exists.

PMID- 9538980
TI  - Association of symptoms of type 2 diabetic patients with severity of disease,
      obesity, and blood pressure.
AB  - OBJECTIVE: The symptoms of 430 type 2 diabetic patients were determined by a self
      administered questionnaire before entry into the U.K. Prospective Diabetes Study.
      RESEARCH DESIGN AND METHODS: Entry into the trial followed 2 months of dietary
      treatment for newly diagnosed patients with type 2 diabetes. Forty symptoms with
      five levels of severity were included in the questionnaire. A complaint rate was
      computed as the sum of symptom scores divided by the number of symptom questions
      answered. RESULTS: The complaint rate was independently and positively related to
      BMI, fasting plasma glucose (FPG), and being a woman. Three symptoms--presence of
      dry mouth (P < 0.001), thirst (P < 0.01), and stomach pain (P = 0.02)--were
      related to FPG independent of sex, age, BMI, or blood pressure. Only dry mouth
      was related to HbA1c (P = 0.05). Complaints of shortness of breath, swollen
      ankles, headaches, heartburn, sweating, wheezing, nocturia, thirst, and diarrhea
      increased with BMI independently of other variables. A complaint of cold
      extremities decreased with BMI. Heartburn, weakness of limbs, and hot flushes
      were positively related to blood pressure, and unsteadiness was negatively
      related. CONCLUSIONS: The symptoms reported by patients with type 2 diabetes
      increased with FPG and markedly with BMI. The symptoms associated with obesity
      have been underestimated in the past.

PMID- 9538979
TI  - Effects of lisinopril and nifedipine on the progression to overt albuminuria in
      IDDM patients with incipient nephropathy and normal blood pressure. The Italian
      Microalbuminuria Study Group in IDDM.
AB  - OBJECTIVE: Intervention trials on renal function in IDDM patients with
      microalbuminuria (MA) should adopt the rate of decline of glomerular filtration
      rate (GFR) as an outcome measure. However, normotensive IDDM patients with MA
      show no change in GFR over a follow-up period of 10 years. Thus, in the present
      study, we used the cumulative incidence of progression to albuminuria (albumin
      excretion rate [AER] > 200 micrograms/min) from MA as the primary endpoint and
      the yearly increase in AER at a rate of 50% above baseline as the secondary end
      point of renal function. RESEARCH DESIGN AND METHODS: Ninety-two normotensive
      IDDM patients underwent double-blind, double-dummy treatment with either
      lisinopril or slow-release nifedipine in comparison with placebo. Ten patients
      discontinued the study during the 3-year follow-up period. RESULTS: During the 3
      year follow-up period, 7 of 34 placebo-treated (20.6%), 2 of 32 lisinopril
      treated (6.3%), and 2 of 26 nifedipine-treated (7.7%) patients progressed to
      clinical albuminuria (Fisher's exact test, P < 0.03). Time-to-event analysis
      indicated a reduction in the risk of progression to macroalbuminuria of 58.1%
      (95% CI 27.8-68.4%) in the 32 patients on lisinopril (P < 0.02) and of 62.5% (95%
      CI 32.5-73.4%) in the 26 patients on nifedipine (P < 0.02) after adjustment for
      mean blood pressure, glycated hemoglobin, and baseline AER in comparison with the
      34 patients on placebo. Baseline AER was 71 micrograms/min (range: 20.7-187.3) in
      progressors and 73 micrograms/min (range: 20.2-174.1) in nonprogressors (NS). The
      percentage of patients who showed a > 50% yearly increase of AER above baseline
      values was significantly lower in the lisinopril group (13 of 32, 40.6%, P <
      0.02), but not in the nifedipine group (15 of 26, 57.7%), than in the placebo
      group (23 of 34, 67.6%). The lisinopril group had significantly lower blood
      pressure values during follow-up than either the nifedipine (P < 0.05) or the
      placebo (P < 0.01) group. CONCLUSIONS: Our data show that both lisinopril and
      nifedipine are effective in delaying the occurrence of macroalbuminuria in
      normotensive IDDM patients with MA. As overt proteinuria strongly predicts end
      stage renal failure, both treatments appear capable of preventing such a
      complication in normotensive IDDM patients with MA. However, lisinopril appears
      more powerful in slowing the course of nephropathy.

PMID- 9538981
TI  - Role of glycemic control and blood pressure in the development and progression of
      nephropathy in elderly Japanese NIDDM patients.
AB  - OBJECTIVE: To investigate the role of glycemic control and blood pressure in the
      development and progression of nephropathy and to suggest goals for glycemic
      control and blood pressure for the prevention of nephropathy in elderly Japanese
      NIDDM patients. RESEARCH DESIGN AND METHODS: A total of 123 age- and diabetes
      duration-matched elderly Japanese NIDDM patients (aged 60-75 years; 74
      normoalbuminuric and 49 microalbuminuric) were retrospectively studied for 6
      years. RESULTS: The group that developed microalbuminuria from normoalbuminuria
      (group NM: n = 24) showed a higher 6-year mean HbA1c than the group that remained
      normoalbuminuric (group NN: n = 50; 9.0 +/- 0.8 vs. 8.1 +/- 0.8%, P < 0.01) in
      spite of no significant difference in 6-year mean blood pressure (MBP). On the
      other hand, the group that progressed from microalbuminuria to overt proteinuria
      (group MP: n = 26) showed a higher 6-year MBP than the group that remained
      microalbuminuric (group MM: n = 23; 106 +/- 5 vs. 95 +/- 6 mmHg, P < 0.01) in
      spite of no significant difference in 6-year mean HbA1c. The cutoff level of
      HbA1c separating group NN from group NM was 8.5% (normal range < or = 6.5%), and
      that of MBP separating group MM from group MP was 100 mmHg. CONCLUSIONS: Glycemic
      control is a more potent factor than blood pressure level on the development of
      microalbuminuria. However, as far as the progression of microalbuminuria to overt
      proteinuria is concerned, hypertension is the most crucial factor in elderly
      NIDDM patients. Suggested goals for glycemic control and blood pressure level for
      the prevention of nephropathy in elderly Japanese patients are an HbA1c of < or =
      8.5% (equivalent to 7.8% in the current measurement of stable HbA1c; normal range
      < or = 5.8%) and an MBP of < or = 100 mmHg.

PMID- 9538982
TI  - Platelet resistance to nitrates in obesity and obese NIDDM, and normal platelet
      sensitivity to both insulin and nitrates in lean NIDDM.
AB  - OBJECTIVE: Previous studies in our laboratory showed that the platelet anti
      aggregating effect exerted by insulin, mediated by a nitric oxide (NO)-induced
      increase of guanosine-3',5'-cyclic monophosphate (cGMP), is lost in the insulin
      resistant of obesity and obese NIDDM. It is not clear 1) whether the alterations
      observed in obese NIDDM patients are attributable to the obesity-related insulin
      resistance or to diabetes per se and 2) whether insulin-resistant states present
      a normal or a blunted response to NO. This study has been conducted to
      investigate 1) the platelet sensitivity to insulin in lean NIDDM and 2) the
      platelet sensitivity to an NO donor, glyceryl trinitrate (GTN), in obesity and in
      both lean and obese NIDDM. RESEARCH DESIGN AND METHODS: We determined 1) ADP
      induced platelet aggregation and platelet cGMP content in platelet-rich plasma
      (PRP) obtained from 11 lean NIDDM patients, after a 3-min incubation with insulin
      (0, 240, 480, 960, 1,920 pmol/l) and 2) ADP-induced platelet aggregation and
      platelet cGMP content in PRP obtained from 9 obese subjects, 11 lean and 8 obese
      NIDDM patients, and 18 control subjects, after a 3-min incubation with 0, 20, 40,
      and 100 mumol/l GTN. RESULTS: Insulin dose-dependently decreased platelet
      aggregation in lean NIDDM patients (P = 0.0001): with 1,920 pmol/l of insulin,
      ADP ED50 was 141.5 +/- 6.4% of basal values (P = 0.0001). Furthermore, insulin
      increased platelet cGMP (P = 0.0001) from 7.5 +/- 0.2 to 21.1 +/- 3.7 pmol/10(9)
      platelets. These results were similar to those previously described in healthy
      subjects. GTN reduced platelet aggregation in all the groups (P = 0.0001) at all
      the concentrations tested (P = 0.0001), but GTN IC50 values were much higher in
      insulin-resistant patients: 36.3 +/- 5.0 mumol/l in healthy control subjects,
      26.0 +/- 6.0 mumol/l in lean NIDDM patients (NS vs. control subjects), 123.6 +/-
      24.0 mumol/l in obese subjects (P = 0.0001 vs. control subjects), and 110.1 +/-
      19.2 mumol/l in obese NIDDM patients (P = 0.0001 vs. control subjects). GTN dose
      dependently increased platelet cGMP in all the groups (P = 0.0001 in control
      subjects, lean NIDDM patients, and obese subjects; P = 0.04 in obese NIDDM
      patients). Values reached by obese subjects and obese NIDDM patients, however,
      were lower than those reached by control subjects (with 100 mumol/l of GTN, P =
      0.001 and P = 0.0001, respectively). In healthy control subjects and in obese
      subjects, the insulin:glucose ratio, used as an indirect measure of insulin
      sensitivity, was positively correlated to GTN IC50 (r = 0.530, P = 0.008),
      further suggesting that the sensitivity to NO is reduced in the presence of
      insulin resistance. CONCLUSIONS: The insulin anti-aggregating effect is preserved
      in lean NIDDM; platelet sensitivity to GTN in preserved in lean NIDDM but is
      reduced in the insulin-resistant states of obesity and obese NIDDM. Resistance to
      nitrates, therefore, could be considered another feature of the insulin
      resistance syndrome.

PMID- 9538983
TI  - Intact proinsulin, des 31,32 proinsulin, and specific insulin concentrations
      among nondiabetic and diabetic subjects in populations at varying risk of type 2
      diabetes.
AB  - OBJECTIVE: To examine hyperinsulinemia, insulin secretion, and beta-cell function
      in Pima Indians, South Asians, and whites, populations at varying risk of
      diabetes. RESEARCH DESIGN AND METHODS: We investigated 136 Pima Indian, 98 Asian,
      and 80 white nondiabetic and 172 Pima Indian, 40 Asian, and 49 white diabetic
      subjects. Highly specific assays for insulin, intact proinsulin, and des 31,32
      proinsulin were used. Insulin secretion was assessed using ratio of increment (0
      to 30 min) in insulin to glucose concentrations during an oral glucose tolerance
      test (OGTT). RESULTS: Nondiabetic Pima Indians were significantly more obese than
      Asians and whites. Pima Indian subjects had significantly higher (P < 0.01)
      fasting insulin concentrations (median 109 pmol/l, range 40-250) than Asian (37
      pmol/l, range 17-91) and white (30 pmol/l, range 10-82) subjects. These
      differences remained significant when controlled for obesity. Nondiabetic Pima
      Indians also had higher fasting C-peptide concentrations and higher early insulin
      secretion during an OGTT. Fasting concentrations of intact proinsulin and des
      31,32 proinsulin were also significantly higher in Pima Indians (P < 0.01).
      However, the proportion of proinsulin-like molecules was significantly lower (P <
      0.01) in Pima Indians (median 7.9% vs. 12.7% for South Asians and 12.2% for
      whites). Subjects with diabetes from the three ethnic groups showed significantly
      higher fasting insulin concentrations but lower 30-min insulin and lower ratios
      of increment (0-30 min) in insulin to glucose concentrations than did nondiabetic
      subjects. The proportion of proinsulin-like molecules was not significantly
      different in diabetic subjects from the three ethnic groups. CONCLUSIONS: These
      specific assays for insulin indicate that after adjusting for obesity nondiabetic
      Pima Indians are truly hyperinsulinemic, which is consistent with their insulin
      resistance as measured by other methods. Hyperinsulinemia in this population with
      a high risk of diabetes is likely to be due to enhanced insulin secretion.
      Furthermore, in Pima Indians, the predominant beta-cell secretory product is
      insulin and not its precursors. We conclude that the differences in the risk of
      diabetes among these three groups are not due to differences in insulin secretion
      or insulin processing. Subjects with type 2 diabetes have defective early insulin
      secretion during OGTTs but show fasting hyperinsulinemia even when specific
      assays for insulin are used.

PMID- 9538984
TI  - Development and progression of diabetic retinopathy in Koreans with NIDDM.
AB  - OBJECTIVE: To determine the incidence and risk factors for the development and
      progression of diabetic retinopathy in Korean patients with NIDDM. RESEARCH
      DESIGN AND METHODS: A total of 186 patients with NIDDM who did not have
      proliferative diabetic retinopathy (PDR) at baseline were prospectively studied
      for 5.3 +/- 1.0 years in an outpatient clinic of a university hospital. The
      incidence and progression of diabetic retinopathy was determined by annual
      funduscopic examination by an ophthalmologist. RESULTS: Of the 130 patients who
      were free of diabetic retinopathy at baseline, 30 developed it, giving an
      incidence of 44.4/1,000 person-years. Age and known duration of diabetes, mean
      fasting plasma glucose, and HbA1 levels during the follow-up period were higher
      in the patients who developed diabetic retinopathy. Of the 56 patients who had
      nonproliferative diabetic retinopathy at baseline, 11 developed PDR, giving an
      incidence of 37.5/1,000 person-years. The patients who progressed to PDR during
      follow-up (progressors) had a higher change of BMI and urinary albumin excretion
      rate at baseline and a higher mean HbA1 during the follow-up period than the
      nonprogressors. Cox proportional hazards analysis revealed that mean HbA1 was the
      only independent risk factor for both the development and progression of diabetic
      retinopathy. CONCLUSIONS: The incidence of PDR in Korean NIDDM patients is
      comparable to that reported in other populations. Poor glycemic control is the
      most important risk factor for both the development and progression of diabetic
      retinopathy in NIDDM patients.

PMID- 9538985
TI  - Fractional esterification rate of HDL particles in patients with type 2 diabetes.
      Relation to coronary heart disease risk factors.
AB  - OBJECTIVE: To study the fractional esterification rate of cholesterol on HDL
      particles (FERHDL) in adults with type 2 diabetes and assess its correlation with
      serum lipids and other coronary heart disease (CHD) risk factors. RESEARCH DESIGN
      AND METHODS: FERHDL was measured in 90 adult (57 men, 33 women) patients by an
      isotopic assay method involving several steps, including preparation of VLDL- and
      LDL-depleted plasma, labeling of the sample with a trace amount of tritiated
      cholesterol, separation of free and esterified cholesterol fractions by
      chromatography post incubation, and subsequent counting of radioactivity in the
      individual fractions. RESULTS: Male patients have higher FERHDL values than their
      female counterparts. When HDL cholesterol was controlled for in a multivariate
      regression analysis, the sex factor was not significant. There was a significant
      positive correlation between FERHDL and plasma total cholesterol (r = 0.32),
      triglycerides (r = 0.82), apolipoprotein B (apo B; r = 0.48), insulin (r = 0.46),
      BMI (r = 0.31), and waist-to-hip ratio (WHR; r = 0.50). There was a negative
      correlation between FERHDL and HDL cholesterol (r = -0.76) and apolipoprotein AI
      (r = -0.60). When both HDL cholesterol and triglycerides were controlled for, the
      only significant correlation was between FERHDL and BMI. CONCLUSIONS: Non-insulin
      requiring type 2 diabetic patients have FERHDL, which correlated positively with
      triglycerides and negatively with HDL cholesterol. The positive correlation of
      FERHDL with serum insulin, WHR, total cholesterol, and apo B, but not that with
      BMI, loses its significance when HDL cholesterol and triglycerides are
      controlled. The sex difference between men and women in FERHDL also loses its
      significance when HDL cholesterol is controlled.

PMID- 9538986
TI  - Diabetic retinopathy.

PMID- 9538987
TI  - Diabetic retinopathy. American Diabetes Association.

PMID- 9538989
TI  - Management of dyslipidemia in adults with diabetes. American Diabetes
      Association.

PMID- 9538988
TI  - Management of dyslipidemia in adults with diabetes.
AB  - Subjects with diabetes have a greatly increased risk of CHD, which is only
      partially related to their elevated glucose. Other factors such as insulin
      resistance and dyslipidemia are likely to be important. The type of dyslipidemia
      that is most characteristic of type 2 diabetic subjects is elevated triglycerides
      and decreased HDL cholesterol levels, although all lipoproteins have
      compositional abnormalities. Surprisingly few good prospective studies of
      lipoprotein levels in relation to CHD have been done in diabetic subjects.
      Available studies suggest that low HDL cholesterol may be the most important risk
      factor for CHD in observational studies. In studies in which total cholesterol
      and triglyceride were done, cholesterol and triglycerides were risk factors for
      CHD, although triglycerides were often a stronger predictor. However, the
      strength of triglyceride as a risk factor for CHD may depend partially on its
      association with other variables (e.g., hypertension, plasminogen activator
      inhibitor 1 [PAI-1], etc.). In clinical trials in diabetic subjects, LDL
      reduction with statins has led to significant reductions in CHD incidence. In
      addition, overall mortality was reduced with statin therapy, although the results
      were not statistically significant. Gemfibrozil has led to reductions in CHD
      incidence in diabetic subjects, although the results were not statistically
      significant perhaps because of low sample size. Regarding lipoproteins and CHD
      risk in diabetic patients, the very positive results of statin trials point to
      LDL cholesterol being more important than previous realized. Apparently, having a
      borderline high LDL cholesterol (between 130 and 160 mg/dl) in a diabetic patient
      is equivalent to a much higher LDL cholesterol in terms of CHD risk for a
      nondiabetic subject. Therefore, the primary target of therapy in diabetic
      patients is lowering LDL cholesterol (or possibly, non-HDL cholesterol). Statins
      are the preferred pharmacological agent in this situation. Once LDL cholesterol
      levels have been lowered, attention can be given to treatment of residual
      hypertriglyceridemia and low HDL. The goal here is weight reduction and increased
      exercise. However, for selected patients, combining a fibric acid (or low-dose
      nicotinic acid) with a statin also can be considered. Reduction of LDL levels
      should take priority over reduction of triglycerides in combined hyperlipidemia
      because of the proven safety of the statin class of drugs as well as greater
      reduction in CHD incidence.

PMID- 9538990
TI  - American Diabetes Association Annual Meeting, 1997. Endothelial dysfunction,
      neuropathy and the diabetic foot, diabetic mastopathy, and erectile dysfunction.

PMID- 9538991
TI  - Seasonality of birth in patients with childhood diabetes in The Netherlands.

PMID- 9538992
TI  - Response to Akhter.

PMID- 9538993
TI  - Infection of continuous subcutaneous insulin infusion site with Mycobacterium
      peregrinum.

PMID- 9538994
TI  - Improved glycemic control in a diabetic patient after discontinuation of
      allopurinol administration.

PMID- 9538995
TI  - Diabetes and risk of adverse events with calcium antagonists.

PMID- 9538996
TI  - Trends in incidence of childhood type 1 diabetes in Malta.

PMID- 9538997
TI  - Can the effectiveness of physical activity programs be improved? Response to
      Clark.

PMID- 9538999
TI  - Transferring aged type 1 diabetic patients from animal to human insulin. A
      randomized study. Investigators of the TRANSFERT Study.

PMID- 9539000
TI  - Failure to find GAD antibodies at birth in children with diabetes.

PMID- 9539001
TI  - Lack of association of factor V Leiden and coronary heart disease in individuals
      with and without diabetes.

PMID- 9539002
TI  - Response to Rosenn et al.

PMID- 9539003
TI  - Environmental signaling: a biological context for endocrine disruption.
AB  - Endogenous and exogenous chemical signals have evolved as a means for organisms
      to respond to physical or biological stimuli in the environment. Sensitivity to
      these signals can make organisms vulnerable to inadvertent signals from
      xenobiotics. In this review we discuss how various chemicals can interact with
      steroid-like signaling pathways, especially estrogen. Numerous compounds have
      estrogenic activity, including steroids, phytoestrogens, and synthetic chemicals.
      We compare bioavailability, metabolism, interaction with receptors, and
      interaction with cell-signaling pathways among these three structurally diverse
      groups in order to understand how these chemicals influence physiological
      responses. Based on their mechanisms of action, chemical steroid mimics could
      plausibly be associated with recent adverse health trends in humans and animals.

PMID- 9539005
TI  - Validation of transgenic mice carrying the human prototype c-Ha-ras gene as a
      bioassay model for rapid carcinogenicity testing.
AB  - Carcinogenicity testing is indispensable for identifying environmental
      carcinogens and for evaluating the safety of drugs in the process of development.
      Conventional 2-year rodent bioassays are one of the most resource-consuming tests
      in terms of animals, time, and costs. Development of rapid carcinogenicity
      testing systems that can assess carcinogenicity within a short period has become
      a social demand and is essential to improve efficacy in the identification of
      environmental carcinogens as well as in the development of new drugs. In this
      review we introduce the rapid carcinogenicity testing system using transgenic
      (Tg) mice carrying the human prototype c-Ha-ras gene, namely rasH2 mouse (CB6F1
      TgHras2 mouse is the same mouse). The studies have been conducted to validate the
      rasH2 mouse as a model for the rapid carcinogenicity testing system. Our current
      validation studies revealed that rasH2 mice are able to detect various types of
      mutagenic carcinogens within 6 months. The rasH2 mice may also be able to detect
      various nonmutagenic carcinogens. The validation studies also revealed that rasH2
      mice are generally much more susceptible to both mutagenic and nonmutagenic
      carcinogens than control non-Tg mice. No significant tumor induction has been
      observed in rasH2 mice with either mutagenic or nonmutagenic noncarcinogens. More
      rapid onset and higher incidence of more malignant tumors can be expected with a
      high probability after treatment with various carcinogens in the rasH2 mice than
      in control non-Tg mice. The rasH2 mouse appears to be a promising candidate as an
      animal model for development of a rapid carcinogenicity testing system.

PMID- 9539006
TI  - In vivo transgenic bioassays and assessment of the carcinogenic potential of
      pharmaceuticals.
AB  - There is general agreement in the scientific community on the need to improve
      carcinogenicity testing and the assessment of human carcinogenic risk and to
      incorporate more information on mechanisms and modes of action into the risk
      assessment process. Advances in molecular biology have identified a growing
      number of genes such as protooncogenes and tumor-suppressor genes that are highly
      conserved across species and are associated with a wide variety of human and
      animal cancers. In vivo transgenic rodent models incorporating such mechanisms
      are used to identify mechanisms involved in tumor formation and as selective
      tests for carcinogens. Transgenic methods can be considered an extension of
      genetic manipulation by selective breeding, which long has been employed in
      science and agriculture. The use of two rodent species in carcinogenicity testing
      is especially important for identifying transspecies carcinogens. The capacity of
      a substance to induce neoplasia across species suggests that the mechanism(s)
      involved in the induction of the neoplasia are conserved and therefore may have
      significance for humans. Based on available information there is sufficient
      experience with some in vivo transgenic rodent carcinogenicity models to support
      their application as complementary second species studies in conjunction with a
      single 2-year rodent carcinogenicity study. The optional substitution of a second
      2-year rodent carcinogenicity study with an alternative study such as an in vivo
      transgenic carcinogenicity study is part of the International Conference on
      Harmonization guidance S1B: Testing for Carcinogenicity of Pharmaceuticals. This
      guidance is intended to be flexible enough to accommodate a wide range of
      possible carcinogenicity assessment models currently under consideration or
      models that may be developed in the future. The use of an in vivo transgenic
      mouse model in place of a second 2-year mouse study will improve the assessment
      of carcinogenic risk by contributing insights into the mechanisms of
      tumorigenesis and potential human relevance not available from a standard 2-year
      bioassay. It is envisioned that this will stimulate the further development of
      more efficient and relevant methods for identifying and assessing potential human
      carcinogenic risk, which will benefit public health.

PMID- 9539007
TI  - The U.S. National Toxicology Program evaluation of transgenic mice as predictive
      models for identifying carcinogens.
AB  - National Institute of Environmental Health Sciences researchers have invested
      considerable effort in exploring the utility of transgenic mice to detect
      carcinogens and study mechanisms of carcinogenesis. Work has assessed several
      mouse models genetically altered to enhance their expression of chemically
      induced tumors. Results with the p53def (hemizygous for the tumor-suppressor
      gene) and the Tg.AC (carrier of an activated H-ras oncogene) mice have been used
      as a basis for a proposed new strategy for identifying chemical carcinogens and
      assessing risk. The U.S. National Toxicology Program is conducting a series of
      studies with these two transgenic strains to further examine their strengths and
      weaknesses for identification of documented rodent and human carcinogens and to
      explore their ability to provide information concerning the effective dosimetry
      for target organ mutation.

PMID- 9539004
TI  - Environmental endocrine disruption: an effects assessment and analysis.
AB  - This report is an overview of the current state of the science relative to
      environmental endocrine disruption in humans, laboratory testing, and wildlife
      species. Background information is presented on the field of endocrinology, the
      nature of hormones, and potential sites for endocrine disruption, with specific
      examples of chemicals affecting these sites. An attempt is made to present
      objectively the issue of endocrine disruption, consider working hypotheses, offer
      opposing viewpoints, analyze the available information, and provide a reasonable
      assessment of the problem. Emphasis is placed on disruption of central nervous
      system--pituitary integration of hormonal and sexual behavioral activity, female
      and male reproductive system development and function, and thyroid function. In
      addition, the potential role of environmental endocrine disruption in the
      induction of breast, testicular, and prostate cancers, as well as endometriosis,
      is evaluated. The interrelationship of the endocrine and immune system is
      documented. With respect to endocrine-related ecological effects, specific case
      examples from the peer-reviewed literature of marine invertebrates and
      representatives of the five classes of vertebrates are presented and discussed.
      The report identifies some data gaps in our understanding of the environmental
      endocrine disruption issue and recommends a few research needs. Finally, the
      report states the U.S. Environmental Protection Agency Science Policy Council's
      interim position on endocrine disruption and lists some of the ongoing activities
      to deal with this matter.

PMID- 9539011
TI  - Selected new developments in asbestos immunotoxicity.
AB  - Research over the past three decades has shown that the mammalian immune system
      can be altered by the occupational exposure of asbestos. Early clinical studies
      generally focused on systemic observations of immune alteration such as the
      number and function of peripheral lymphocytes and monocytes. More recently as the
      regulatory influence of local immunity in health and disease becomes more
      defined, immunologic changes occurring in the lung, the primary target organ of
      asbestos, have been significant areas of investigation. This review will focus on
      recent studies that examine the influence of asbestos on pulmonary immunity as
      well as the role of host immune competence in asbestos-related disease.

PMID- 9539008
TI  - Integrated defense system overlaps as a disease model: with examples for multiple
      chemical sensitivity.
AB  - The central nervous, immune, and endocrine systems communicate through multiple
      common messengers. Over evolutionary time, what may be termed integrated defense
      system(s) (IDS) have developed to coordinate these communications for specific
      contexts; these include the stress response, acute-phase response, nonspecific
      immune response, immune response to antigen, kindling, tolerance, time-dependent
      sensitization, neurogenic switching, and traumatic dissociation (TD). These IDSs
      are described and their overlap is examined. Three models of disease production
      are generated: damage, in which IDSs function incorrectly;
      inadequate/inappropriate, in which IDS response is outstripped by a changing
      context; and evolving/learning, in which the IDS learned response to a context is
      deemed pathologic. Mechanisms of multiple chemical sensitivity (MCS) are
      developed from several IDS disease models. Model 1A is pesticide damage to the
      central nervous system, overlapping with body chemical burdens, TD, and chronic
      zinc deficiency; model 1B is benzene disruption of interleukin-1, overlapping
      with childhood developmental windows and hapten-antigenic spreading; and model 1C
      is autoimmunity to immunoglobulin-G (IgG), overlapping with spreading to other
      IgG-inducers, sudden spreading of inciters, and food-contaminating chemicals.
      Model 2A is chemical and stress overload, including comparison with the
      susceptibility/sensitization/triggering/spreading model; model 2B is genetic
      mercury allergy, overlapping with: heavy metals/zinc displacement and
      childhood/gestational mercury exposures; and model 3 is MCS as evolution and
      learning. Remarks are offered on current MCS research. Problems with clinical
      measurement are suggested on the basis of IDS models. Large-sample patient self
      report epidemiology is described as an alternative or addition to clinical
      biomarker and animal testing.

PMID- 9539012
TI  - Stepping backward to improve assessment of PCB congener toxicities.
AB  - Polychlorinated biphenyls (PCBs) are ubiquitous global contaminants that have
      been intensively investigated for three decades. They are broad-acting toxicants
      occurring in complex mixtures and accurate risk assessment has proven to be
      elusive. Focusing on a limited set of end points and emphasizing a fixed set of
      congeners have led to more streamlined data sets that are meant to expedite
      hazard characterization and risk assessment for the most potent congeners--aryl
      hydrocarbon receptor (AhR) agonists. Unfortunately, this has made it impossible
      to confirm or deny significant contributions from the more prevalent components
      of the mixtures. PCBs may be only coincidentally present, rather than causal, in
      some diseases. Still, attempts to determine associations with incomplete residue
      data may lead to erroneous conclusions and make accurate risk assessment even
      more elusive. Responses not mediated through the AhR are presented and emphasize
      large data gaps. Dissimilar analytical reports emphasize that selection of
      analytes is not consistent. Collectively, these data confirm that AhR-focused
      objectives unintentionally created the impression that nonplanar PCBs have little
      if any potential for hazards to humans and wildlife. Near steady-state exposure
      of healthy adults are probably of minor consequence except for emerging
      correlations with non-Hodgkin's lymphoma; however, pulses of exposure to more
      labile mixtures may contribute to developmental effects without leaving a residue
      record. More broadly based criteria are suggested and harmonization of data
      collection and presentation are desirable. A more comprehensive list of PCB
      congeners is proposed that would provide more adequate data upon which to base
      associations with adverse outcomes.

PMID- 9539009
TI  - Rodent models of cardiopulmonary disease: their potential applicability in
      studies of air pollutant susceptibility.
AB  - The mechanisms by which increased mortality and morbidity occur in individuals
      with preexistent cardiopulmonary disease following acute episodes of air
      pollution are unknown. Studies involving air pollution effects on animal models
      of human cardiopulmonary diseases are both infrequent and difficult to interpret.
      Such models are, however, extensively used in studies of disease pathogenesis.
      Primarily they comprise those developed by genetic, pharmacologic, or surgical
      manipulations of the cardiopulmonary system. This review attempts a comprehensive
      description of rodent cardiopulmonary disease models in the context of their
      potential application to susceptibility studies of air pollutants regardless of
      whether the models have been previously used for such studies. The pulmonary
      disease models include bronchitis, emphysema, asthma/allergy, chronic obstructive
      pulmonary disease, interstitial fibrosis, and infection. The models of systemic
      hypertension and congestive heart failure include: those derived by genetics
      (spontaneously hypertensive, Dahl S. renin transgenic, and other rodent models);
      congestive heart failure models derived by surgical manipulations; viral
      myocarditis; and cardiomyopathy induced by adriamycin. The characteristic
      pathogenic features critical to understanding the susceptibility to inhaled
      toxicants are described. It is anticipated that this review will provide a ready
      reference for the selection of appropriate rodent models of cardiopulmonary
      diseases and identify not only their pathobiologic similarities and/or
      differences to humans but also their potential usefulness in susceptibility
      studies.

PMID- 9539010
TI  - In vitro techniques for the assessment of neurotoxicity.
AB  - Risk assessment is a process often divided into the following steps: a) hazard
      identification, b) dose-response assessment, c) exposure assessment, and d) risk
      characterization. Regulatory toxicity studies usually are aimed at providing data
      for the first two steps. Human case reports, environmental research, and in vitro
      studies may also be used to identify or to further characterize a toxic hazard.
      In this report the strengths and limitations of in vitro techniques are discussed
      in light of their usefulness to identify neurotoxic hazards, as well as for the
      subsequent dose-response assessment. Because of the complexity of the nervous
      system, multiple functions of individual cells, and our limited knowledge of
      biochemical processes involved in neurotoxicity, it is not known how well any in
      vitro system would recapitulate the in vivo system. Thus, it would be difficult
      to design an in vitro test battery to replace in vivo test systems. In vitro
      systems are well suited to the study of biological processes in a more isolated
      context and have been most successfully used to elucidate mechanisms of toxicity,
      identify target cells of neurotoxicity, and delineate the development and
      intricate cellular changes induced by neurotoxicants. Both biochemical and
      morphological end points can be used, but many of the end points used can be
      altered by pharmacological actions as well as toxicity. Therefore, for many of
      these end points it is difficult or impossible to set a criterion that allows one
      to differentiate between a pharmacological and a neurotoxic effect. For the
      process of risk assessment such a discrimination is central. Therefore, end
      points used to determine potential neurotoxicity of a compound have to be
      carefully selected and evaluated with respect to their potential to discriminate
      between an adverse neurotoxic effect and a pharmacologic effect. It is obvious
      that for in vitro neurotoxicity studies the primary end points that can be used
      are those affected through specific mechanisms of neurotoxicity. For example, in
      vitro systems may be useful for certain structurally defined compounds and
      mechanisms of toxicity, such as organophosphorus compounds and delayed
      neuropathy, for which target cells and the biochemical processes involved in the
      neurotoxicity are well known. For other compounds and the different types of
      neurotoxicity, a mechanism of toxicity needs to be identified first. Once
      identified, by either in vivo or in vitro methods, a system can be developed to
      detect and to evaluate predictive ability for the type of in vivo neurotoxicity
      produced. Therefore, in vitro tests have their greatest potential in providing
      information on basic mechanistic processes in order to refine specific
      experimental questions to be addressed in the whole animal.

PMID- 9539013
TI  - Methylcyclopentadienyl manganese tricarbonyl: health risk uncertainties and
      research directions.
AB  - With the way cleared for increased use of the fuel additive
      methylcyclopentadienyl manganese tricarbonyl (MMT) in the United States, the
      issue of possible public health impacts associated with this additive has gained
      greater attention. In assessing potential health risks of particulate Mn emitted
      from the combustion of MMT in gasoline, the U.S. Environmental Protection Agency
      not only considered the qualitative types of toxic effects associated with
      inhaled Mn, but conducted extensive exposure-response analyses using various
      statistical approaches and also estimated population exposure distributions of
      particulate Mn based on data from an exposure study conducted in California when
      MMT was used in leaded gasoline. Because of limitations in available data and the
      need to make several assumptions and extrapolations, the resulting risk
      characterization had inherent uncertainties that made it impossible to estimate
      health risks in a definitive or quantitative manner. To support an improved
      health risk characterization, further investigation is needed in the areas of
      health effects, emission characterization, and exposure analysis.

PMID- 9539017
TI  - Health impacts of climate change and ozone depletion: an ecoepidemiologic
      modeling approach.
AB  - Anthropogenic climate changes and stratospheric ozone depletion affect human
      health in various ways. Current mainstream epidemiologic research methods do not
      appear well adapted to analyze these health impacts, which involve complex
      systems influenced by human interventions or simpler processes that will take
      place in the future. This paper discusses a different paradigm for studying the
      health impacts of global environmental changes and focuses on the development of
      integrated ecoepidemiologic models using three examples--the effect of climate
      change on vector-borne diseases, the effect of climate change on thermal-related
      mortality, and the effects of increasing ultraviolet levels because of ozone
      depletion on the rates of skin cancer.

PMID- 9539015
TI  - Soil is an important pathway of human lead exposure.
AB  - This review shows the equal or greater importance of leaded gasoline-contaminated
      dust compared to lead-based paint to the child lead problem, and that soil lead,
      resulting from leaded gasoline and pulverized lead-based paint, is at least or
      more important than lead-based paint (intact and not pulverized) as a pathway of
      human lead exposure. Because lead-based paint is a high-dose source, the
      biologically relevant dosage is similar to lead in soil. Both lead-based paint
      and soil lead are associated with severe lead poisoning. Leaded gasoline and lead
      in food, but not lead-based paint, are strongly associated with population blood
      lead levels in both young children and adults. Soil lead and house dust, but not
      lead-based paint, are associated with population blood lead levels in children.
      Most soil lead and house dust are associated with leaded gasoline. Lead-based
      paint dust is associated with cases of renovation of either exterior or interior
      environments in which the paint was pulverized. Based upon the limited data to
      date, abatement of soil lead is more effective than abatement of lead-based paint
      in reducing blood lead levels of young children. About equal numbers of children
      under 7 years of age are exposed to soil lead and lead-based paint. Seasonality
      studies point to soil lead as the main source of population blood lead levels.
      Soil lead is a greater risk factor than lead-based paint to children engaged in
      hand-to-mouth and pica behavior. In summary, soil lead is important for
      addressing the population of children at risk of lead poisoning. When soil lead
      is acknowledged by regulators and the public health community as an important
      pathway of human lead exposure, then more effective opportunities for improving
      primary lead prevention can become a reality.

PMID- 9539018
TI  - Solvent replacement for green processing.
AB  - The implementation of the Montreal Protocol, the Clean Air Act, and the Pollution
      Prevention Act of 1990 has resulted in increased awareness of organic solvent use
      in chemical processing. The advances made in the search to find "green"
      replacements for traditional solvents are reviewed, with reference to solvent
      alternatives for cleaning, coatings, and chemical reaction and separation
      processes. The development of solvent databases and computational methods that
      aid in the selection and/or design of feasible or optimal environmentally benign
      solvent alternatives for specific applications is also discussed.

PMID- 9539019
TI  - The adaptive response in radiobiology: evolving insights and implications.
AB  - The first of the regularly reproducible experiments to show that very low doses
      of ionizing radiation, like very low doses of chemical agents, could induce
      mechanisms whereby cells become better fit to cope with subsequent exposures to
      high doses were carried out on the induction of chromosome aberrations in
      cultures of human lymphocytes. If cells that had been exposed to a very low dose
      (1 cGy) of X rays were subsequently exposed to a relatively high dose (1 Gy),
      approximately half as many chromosome breaks were induced. Subsequent experiments
      showed that this adaptive response to low doses requires a certain minimal dose
      before it becomes active; occurs only within a relatively small window of dose;
      is dose-rate dependent; and depends on the genetic constitution of the people or
      animals exposed, with some being unresponsive. It was further shown that the
      response to the low-dose preexposure was not instantaneous but took approximately
      4 to 6 hr to become fully active, and could be prevented if during this period
      protein synthesis was inhibited, i.e., a necessary protein (enzyme) was being
      induced. In fact, subsequent experiments with two-dimensional gel electrophoresis
      showed new proteins in cells irradiated with 1 to 2 cGy. The adaptation induced
      by low doses of radiation was therefore attributed to the induction of a novel
      efficient chromosome break repair mechanism that if active at the time of
      challenge with high doses would lead to less residual damage. This hypothesis was
      strengthened by a series of experiments in which it was found that inhibitors of
      poly(ADP-ribose)polymerase, an enzyme implicated in DNA strand break rejoining,
      could prevent the adaptive response. Although the phenomenon is well established
      in cellular systems, it is still problematical as to whether or not it will have
      any utility in establishing risks of ionizing radiation to humans. Newer
      experiments have now been carried out on the mechanisms underlying the effect and
      whether or not the effect can manifest itself as a decrease in the number of
      induced cancers and radiation-induced mortality. Experiments with restriction
      enzymes now indicate that double-strand breaks in DNA can be triggering events in
      adaptation. In addition, preliminary experiments on the survival of whole-body
      irradiated mice have shown that multiple exposures to low adapting doses can have
      profound effects on survival, and other experiments have shown that adaptation
      can affect the induction of thymic lymphoma in irradiated mice. It therefore
      appears that the initial experiments behind the adaptive response have led to a
      vigorous worldwide effort to understand the basic mechanisms behind it. This
      effort is stimulated both by a desire to understand the basic cell biology behind
      the response and a desire to see if indeed this phenomenon affects the estimation
      of risks of low-level radiation exposure.

PMID- 9539016
TI  - Effect of glutathione S-transferase M1 polymorphisms on biomarkers of exposure
      and effects.
AB  - Genotypes responsible for interindividual differences in ability to activate or
      detoxify genotoxic agents are recognized as biomarkers of susceptibility. Among
      the most studied genotypes are human glutathione transferases. The relationship
      of genetic susceptibility to biomarkers of exposure and effects was studied
      especially in relation to the genetic polymorphism of glutathione S-transferase
      M1 (GSTM1). For this review papers reporting the effect of GSTM1 genotype on DNA
      adducts, protein adducts, urine mutagenicity, Comet assay parameters, chromosomal
      aberrations, sister chromatid exchanges (SCE), micronuclei, and hypoxanthine
      guanine phosphoribosyl transferase mutations were assessed. Subjects in groups
      occupationally exposed to polycyclic aromatic hydrocarbons, benzidine,
      pesticides, and 1,3-butadiene were included. As environmentally exposed
      populations, autopsy donors, coal tar-treated patients, smokers, nonsmokers,
      mothers, postal workers, and firefighters were followed. From all biomarkers the
      effect of GSTM1 and N-acetyl transferase 2 was seen in coke oven workers on
      mutagenicity of urine and of glutathione S-transferase T1 on the chromosomal
      aberrations in subjects from 1,3-butadiene monomer production units. Effects of
      genotypes on DNA adducts were found from lung tissue of autopsy donors and from
      placentas of mothers living in an air-polluted region. The GSTM1 genotype
      affected mutagenicity of urine in smokers and subjects from polluted regions,
      protein adducts in smokers, SCE in smokers and nonsmokers, and Comet assay
      parameters in postal workers. A review of all studies on GSTM1 polymorphisms
      suggests that research probably has not reached the stage where results can be
      interpreted to formulate preventive measures. The relationship between genotypes
      and biomarkers of exposure and effects may provide an important guide to the risk
      assessment of human exposure to mutagens and carcinogens.

PMID- 9539014
TI  - Effects of micronutrients on metal toxicity.
AB  - There is growing evidence that micronutrient intake has a significant effect on
      the toxicity and carcinogenesis caused by various chemicals. This paper examines
      the effect of micronutrient status on the toxicity of four nonessential metals:
      cadmium, lead, mercury, and arsenic. Unfortunately, few studies have directly
      examined the effect of dietary deficiency or supplementation on metal toxicity.
      More commonly, the effect of dietary alteration must be deduced from the results
      of mechanistic studies. We have chosen to separate the effect of micronutrients
      on toxic metals into three classes: interaction between essential micronutrients
      and toxic metals during uptake, binding, and excretion; influence of
      micronutrients on the metabolism of toxic metals; and effect of micronutrients on
      secondary toxic effects of metals. Based on data from mechanistic studies, the
      ability of micronutrients to modulate the toxicity of metals is indisputable.
      Micronutrients interact with toxic metals at several points in the body:
      absorption and excretion of toxic metals; transport of metals in the body;
      binding to target proteins; metabolism and sequestration of toxic metals; and
      finally, in secondary mechanisms of toxicity such as oxidative stress. Therefore,
      people eating a diet deficient in micronutrients will be predisposed to toxicity
      from nonessential metals.

PMID- 9539020
TI  - The traditional toxicologic paradigm is correct: dose influences mechanism.
AB  - Dose influences mechanism; and over a wide range of doses, one can envision that
      mechanism will change with changing dose. This basic concept in toxicology is
      juxtaposed with the biologic importance of maintaining normal DNA methylation
      status to provide the focus of this paper. The idea that altered DNA methylation
      plays a variety of roles in carcinogenesis is compatible with three key features
      of this multistage process: clonal selection of abnormal cells in a progressive
      fashion, the reversibility of tumor promotion, and the multiplicity of tumor
      phenotypes. A relatively low capacity to maintain normal methylation status
      appears to explain, in part, the high propensity of the B6C3F1 mouse to develop
      liver tumors. This observation supports the view that a mouse liver tumor
      response is not an appropriate end point for human risk assessment. Additionally,
      it is suggested that altered DNA methylation can be viewed as a secondary
      mechanism underlying carcinogenesis. The knowledge that a chemical is acting by a
      mode of action involving a secondary mechanism can be used to support a safety
      factor or multiplicity of exposure approach to risk assessment.

PMID- 9539021
TI  - The role of oxidative stress in chemical carcinogenesis.
AB  - Oxidative stress results when the balance between the production of reactive
      oxygen species (ROS) overrides the antioxidant capability of the target cell;
      oxidative damage from the interaction of reactive oxygen with critical cellular
      macromolecules may occur. ROS may interact with and modify cellular protein,
      lipid, and DNA, which results in altered target cell function. The accumulation
      of oxidative damage has been implicated in both acute and chronic cell injury
      including possible participation in the formation of cancer. Acute oxidative
      injury may produce selective cell death and a compensatory increase in cell
      proliferation. This stimulus may result in the formation of newly initiated
      preneoplastic cells and/or enhance the selective clonal expansion of latent
      initiated preneoplastic cells. Similarly, sublethal acute oxidative injury may
      produce unrepaired DNA damage and result in the formation of new mutations and,
      potentially, new initiated cells. In contrast, sustained chronic oxidative injury
      may lead to a nonlethal modification of normal cellular growth control
      mechanisms. Cellular oxidative stress can modify intercellular communication,
      protein kinase activity, membrane structure and function, and gene expression,
      and result in modulation of cell growth. We examined the role of oxidative stress
      as a possible mechanism by which nongenotoxic carcinogens may function. In
      studies with the selective mouse liver carcinogen dieldrin, a species-specific
      and dose-dependent decrease in liver antioxidant concentrations with a
      concomitant increase in ROS formation and oxidative damage was seen. This
      increase in oxidative stress correlated with an increase in hepatocyte DNA
      synthesis. Antioxidant supplementation prevented the dieldrin-induced cellular
      changes. Our findings suggest that the effect of nongenotoxic carcinogens (if
      they function through oxidative mechanisms) may be amplified in rodents but not
      in primates because of rodents' greater sensitivity to ROS. These results and
      findings reported by others support a potential role for oxidative-induced injury
      in the cancer process specifically during the promotion stage.

PMID- 9539022
TI  - Induction of metallothionein as an adaptive mechanism affecting the magnitude and
      progression of toxicological injury.
AB  - Pretreatment of rats with low doses of Cd produces adaptive tolerance to a
      subsequent high dose of Cd-induced lethality, thus shifting the dose-response
      curve to the right. Cd pretreatment of animals also protects against the
      hepatotoxicity produced by high doses of Cd. This protection is attributable to
      the 10- to 50-fold induction of hepatic metallothionein (MT) by Cd pretreatment.
      As a result hepatic subcellular distribution of Cd is significantly altered, with
      more Cd bound to MT in the cytosol and a concomitant reduction of Cd in other
      critical organelles. In addition MT-transgenic animals are more resistant,
      whereas MT-null mice are more sensitive than controls to Cd-induced lethality and
      hepatotoxicity. This further demonstrates that MT is important in Cd
      detoxication. Induction of hepatic MT by zinc also protects mice from carbon
      tetrachloride (CCl4)-induced liver injury, with more 14C-CCl4 bound to MT in the
      cytosol. MT-null mice are more sensitive to CCl4-induced hepatotoxicity, which
      supports the hypothesis that induction of MT also plays a protective role for
      nonmetallic chemicals. These results indicate that MT is a part of cellular
      adaptive mechanisms affecting the magnitude and progression of toxic insults from
      metals such as Cd as well as from organic chemicals such as CCl4.

PMID- 9539023
TI  - DNA-dependent protein kinase does not play a role in adaptive survival responses
      to ionizing radiation.
AB  - We previously demonstrated that exposure of certain human tumor cells to very low
      chronic doses of ionizing radiation led to their enhanced survival following
      exposure to subsequent high doses of radiation. Survival enhancement due to these
      adaptive survival responses (ASRs) ranged from 1.5-fold to 2.2-fold in many human
      tumor cells. Furthermore, we showed that ASRs result from altered G1 checkpoint
      regulation, possibly mediated by overexpression of cyclin D1, proliferating cell
      nuclear antigen (PCNA), and the X-ray induction of cyclin A. Because cyclin D1
      and PCNA proteins are components of many DNA synthetic and repair processes in
      the cell, we tested the hypothesis that preexposure of cells to low doses of
      ionizing radiation enabled activation of the DNA repair machinery needed for
      survival recovery after high-dose radiation. We examined the role of DNA break
      repair in ASRs using murine cells deficient (i.e., severe combined
      immunodeficiency [SCID] cells) or proficient (i.e., parental mouse strain [CB-17]
      cells) in DNA-dependent protein kinase catalytic subunit (DNA-PKcs) expression
      and DNA double-strand break repair, DNA-PKcs is a nuclear serine/threonine
      protein kinase that is activated by DNA breaks and plays a key role in double
      strand break repair. DNA-PKcs also phosphorylates several nuclear DNA-binding
      regulatory transcription factor proteins (e.g., Sp1 and p53), which suggests that
      DNA-PKcs may play a role in regulating transcription, replication, and
      recombination as well as DNA repair, after radiation. Therefore, we exposed
      confluent SCID or CB-17 cells to low priming doses of ionizing radiation (i.e., 5
      cGy) and compared the survival responses of primed cells to those of unprimed
      cells after an equitoxic high-dose challenge. Low-dose-primed SCID or CB-17 cells
      demonstrated 2-fold enhanced survival after a high-dose challenge compared to
      that of unprimed control cells. These data suggest that expression of the
      catalytic subunit of DNA-PKcs (expressed in CB-17 not SCID cells) and the
      presence of active double-strand break repair processes (active in CB-17,
      deficient in SCID cells) do not play a major role in ASRs in mammalian cells.
      Furthermore, we present data that suggest that DNA-PKcs plays a role in the
      regulation of the G2/M cell cycle checkpoint following extremely high doses of
      ionizing radiation.

PMID- 9539024
TI  - Upregulation of apoptosis with dietary restriction: implications for
      carcinogenesis and aging.
AB  - The maintenance of cell number homeostasis in normal tissues reflects a highly
      regulated balance between the rates of cell proliferation and cell death. Under
      pathologic conditions such as exposure to cytotoxic, genotoxic, or nongenotoxic
      agents, an imbalance in these rates may indicate subsequent risk of
      carcinogenesis. Apoptotic cell death, as opposed to necrotic cell death, provides
      a protective mechanism by selective elimination of senescent, preneoplastic, or
      superfluous cells that could negatively affect normal function and/or promote
      cell transformation. The relative efficiency or dysfunction of the cell death
      program could therefore have a direct impact on the risk of degenerative or
      neoplastic disease. Dietary restriction of rodents is a noninvasive intervention
      that has been reproducibly shown to retard tumor development and most physiologic
      indices of aging relative to ad libitum-fed animals. As such, it provides a
      powerful model in which to study common mechanistic processes associated with
      both aging and cancer. In a recent study we established that chronic dietary
      restriction (DR) induces an increase in spontaneous apoptotic rate and a decrease
      in cell proliferation rate in hepatocytes of 12-month-old B6C3F1 DR mice relative
      to ad libitum (AL)-fed mice. This diet-induced shift in cell death/proliferation
      rates was associated with a marked reduction in subsequent development of
      spontaneous hepatoma and a marked increase in disease-free life span in DR
      relative to AL-fed mice. These results suggest that total caloric intake may
      modulate the rates of cell death and proliferation in a direction consistent with
      a cancer-protective effect in DR mice and a cancer-promoting effect in AL mice.
      To determine whether the increase in spontaneous apoptotic rate was maintained
      over the life span of DR mice, apoptotic rates were quantified in 12-, 18-, 24-
      and 30-month-old DR and AL mice. The rate of apoptosis was elevated with age in
      both diet groups; however, the rate of apoptosis was significantly and
      consistently higher in DR mice regardless of age. In double-labeling experiments,
      an age-associated increase in the glutathione S-transferase-II expression in
      putative preneoplastic hepatocytes in AL mice was rapidly reduced by apoptosis
      upon initiation of DR. Thus, intervention that promote a low-level increase in
      apoptotic cell death may be expected to protect genotypic and phenotypic
      stability with age. If during tumor promotion an adaptive increase in apoptosis
      effectively balances the dysregulated increase proliferation, the risk of
      permanent genetic error and carcinogenesis would be minimized.

PMID- 9539026
TI  - Exercise-induced stress response as an adaptive tolerance strategy.
AB  - Interaction between the quality of the environment and the health of the exposed
      population determines the survival response of living organisms. The phenomenon
      of induced tolerance by exposure to threshold levels of stressors to stimulate
      natural defense mechanisms has potential therapeutic value. The paucity of
      information on predictability of individual response and information on the
      operative fundamental mechanisms limit applicability of the adaptive tolerance
      strategy. A potential biomarker of the stress response includes members of the
      stress-inducible ubiquitin gene family. Transcript sizes detected with Northern
      blot analysis identify different classes of ubiquitin gene family members and the
      intensity of the radioactive signal allows abundance determinations. Using
      moderate exercise as the stressor, significant increase (p < 0.028) in abundance
      of inducible polyubiquitin genes was found in human blood. Both the potential of
      exercise as a model system of a natural stress inducer and polyubiquitin as a
      biomarker of stress were established in these studies.

PMID- 9539028
TI  - Modeling to incorporate defense mechanisms into the estimation of dose responses.
AB  - Several adverse health effects (including cancer and noncancer effects) may be
      the result of an imbalance between exogenous and endogenous invading substances
      and defense mechanisms. In these cases the probability of an adverse effect
      depends on how much the exposure to a substance increases or decreases the number
      of defenders or their efficiency as well as increasing or decreasing the number
      of invaders. Rather than using a dose scale such as parts per million or
      milligram/kilogram/day in these cases, dose-response models can directly
      incorporate the impact of defense mechanisms by using a dose scale that
      corresponds to the number of invaders that break through the defenders and become
      free to do their damage. The number of breakthroughs at a specific age, the
      cumulative number of breakthroughs by a specific age, or the cumulative number of
      breakthroughs in a window of time would usually be the appropriate age-dependent
      dose. Although a lifetime average daily dose level can be used as a surrogate for
      an age-dependent dose in simplistic dose-response models, the age-dependent dose
      itself can be used in more biologically based models that include time, reflect
      the key role of feedback mechanisms, and treat the human body as an age-dependent
      dynamic system responding to internal and external stimuli and not as a system at
      equilibrium. Some illustrative biologic examples of defense mechanisms and
      invader-defender interactions are presented. Several numerical examples are given
      in which the dose incorporates the age-dependent effects of a substance on the
      number of invaders, the number of defenders, and/or the defenders' efficiencies.

PMID- 9539027
TI  - Hierarchical and cybernetic nature of biologic systems and their relevance to
      homeostatic adaptation to low-level exposures to oxidative stress-inducing
      agents.
AB  - During evolution in an aerobic environment, multicellular organisms survived by
      adaptive responses to both the endogenous oxidative metabolism in the cells of
      the organism and the chemicals and low-level radiation to which they had been
      exposed. The defense repertoire exists at all levels of the biological hierarchy-
      from the molecular and biochemical level to the cellular and tissue level to the
      organ and organ system level. Cells contain preventive antioxidants to suppress
      oxidative damage to membranes. Cells also contain proteins and DNA; built-in
      redundancies for damaged molecules and organelles; tightly coupled redox systems;
      pools of reductants; antioxidants; DNA repair mechanisms and sensitive sensor
      molecules such as nuclear factor kappa beta; and signal transduction mechanisms
      affecting both transcription and post-translational modification of proteins
      needed to cope with oxidative stress. The biologic consequences of the low-level
      radiation that exceeds the background level of oxidative damage could be necrosis
      or apoptosis, cell proliferation, or cell differentiation. These effects are
      triggered by oxidative stress-induced signal transduction mechanisms--an
      epigenetic, not genotoxic, process. If the end points of cell proliferation,
      differentiation, or cell death are not seen at frequencies above background
      levels in an organism, it is unlikely that low-level radiation would play a role
      in the multistep processes of chronic diseases such as cancer. The mechanism
      linked to homeostatic regulation of proliferation and adaptive functions in a
      multicellular organism could provide protection of any one cell receiving
      deposited energy by the radiation tract through the sharing of reductants and by
      triggering apoptosis of target stem cells. Examples of the role of gap junctional
      intercellular communication in the adaptive response of cells and the bystander
      effect illustrate how the interaction of cells can modulate the effect of
      radiation on the single cell.

PMID- 9539025
TI  - Caloric restriction as a mechanism mediating resistance to environmental disease.
AB  - It has been observed that susceptibility to many degenerative diseases increases
      concurrently with industrialization and rising living standards. Although
      epidemiologic studies suggest that specific environmental and dietary factors may
      be important, caloric intake alone (as reflected in body size) may account for
      much of the differential risk observed among diverse human populations. It has
      been suggested from animal studies that caloric intake may be the primary
      effector for many hormonal, metabolic, physiologic, and behavioral responses that
      coordinate reproductive strategy to apparent availability of food. When caloric
      intake is excessive, particularly at critical developmental stages, physiologic
      priorities are set for body growth and fecundity rather than for endurance and
      longevity. The converse occurs during periods of famine, thus increasing the
      probability that sufficient individuals survive to restore the population when
      conditions improve. Calorically restricted rodents have significantly longer
      reproductive and total life spans than their ad libitum-fed controls and exhibit
      a spectrum of biochemical and physiologic alterations that characterize their
      adaptation to reduced intake. These include reduced stature, hypercorticism in
      the absence of elevated adrenocorticotropic hormone levels, increased metabolic
      efficiency, decreased mitogenic response coupled with increased rates of
      apoptosis, reduced inflammatory response, induction of stress proteins and DNA
      repair enzymes, altered drug-metabolizing enzyme expression, and modified cell
      mediated immune function. The overall profile of these changes is one of improved
      defense against environmental stress. This has been suggested as the mechanistic
      basis for the protective effects of low body weight on radiation and chemically
      induced cancers in experimental animals. It may also explain the significantly
      higher thresholds of acute toxicity observed when calorically restricted rodents
      are exposed to certain test compounds.

PMID- 9539029
TI  - The use of biochemical and molecular parameters to estimate dose-response
      relationships at low levels of exposure.
AB  - Biomarkers based on alterations in molecular and biochemical parameters may be
      useful in chemical risk assessment for establishing the presence of an exposure,
      ranking relative risks among exposed individuals, and estimating risks at low
      levels of exposure. Because it is unlikely that the relation between toxic
      responses and the degree of alteration in the biomarker is equivalent at all
      doses, quantification of risks at low levels is not necessarily more accurate
      using these biomarkers for extrapolation. The application of response biomarkers
      for risk evaluation at low levels of exposure is discussed in relation to 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD), a compound that causes induction of
      cytochromes CYP1A1 and CYP1A2 in liver and other tissues. CYP1A1 induction in
      liver increases monotonically with TCDD dosage; however, several of the dose
      response curves for hepatic effects of TCDD are U-shaped. The U-shaped dose
      response curve for hepatic tumor promotion appears to result because the
      integrated toxicologic response depends on multiple underlying processes-
      mitosuppression, toxicity, and cell proliferation--each of which has a different
      dose-response relationship with respect to TCDD. Although dose-response
      relationships for the biomarkers are not expected to duplicate the complex shapes
      seen with the integrated responses, measurements and pharmacodynamic modeling of
      the changes in these molecular and biochemical parameters can still be useful for
      obtaining an upperbound risk estimate at low levels of exposure.

PMID- 9539030
TI  - Hormesis as a biological hypothesis.
AB  - A comprehensive effort was undertaken to identify articles demonstrating chemical
      hormesis. Nearly 4000 potentially relevant articles were retrieved from
      preliminary computer database searches by using various key word descriptors and
      extensive cross-referencing. A priori evaluation criteria were established
      including study design features (e.g., number of doses, dose range), statistical
      analysis, and reproducibility of results. Evidence of chemical hormesis was
      judged to have occurred in approximately 350 of the 4000 studies evaluated.
      Chemical hormesis was observed in a wide range of taxonomic groups and involved
      agents representing highly diverse chemical classes, many of potential
      environmental relevance. Numerous biological end points were assessed; growth
      responses were the most prevalent, followed by metabolic effects, longevity,
      reproductive responses, and survival. Hormetic responses were generally observed
      to be of limited magnitude. The average low-dose maximum stimulation was
      approximately 50% greater than controls. The hormetic dose-response range was
      generally limited to about one order of magnitude, with the upper end of the
      hormetic curve approaching the estimated no observable effect level for the
      particular end point. Based on the evaluation criteria, high to moderate evidence
      of hormesis was observed in studies comprised of > 6 doses; with > 3 doses in the
      hormetic zone. The present analysis suggests that chemical hormesis is a
      reproducible and relatively common biological phenomenon. A quantitative scheme
      is presented for future application to the database.

PMID- 9539031
TI  - Nonlinearity of radiation health effects.
AB  - The prime concern of radiation protection policy since 1959 has been to protect
      DNA from damage. In 1994 the United Nations Scientific Community on the Effects
      of Atomic Radiation focused on biosystem response to radiation with its report
      Adaptive Responses to Radiation of Cells and Organisms. The 1995 National Council
      on Radiation Protection and Measurements report Principles and Application of
      Collective Dose in Radiation Protection states that because no human data
      provides direct support for the linear nonthreshold hypothesis (LNT), confidence
      in LNT is based on the biophysical concept that the passage of a single charged
      particle could cause damage to DNA that would result in cancer. Several
      statistically significant epidemiologic studies contradict the validity of this
      concept by showing risk decrements, i.e., hormesis, of cancer mortality and
      mortality from all causes in populations exposed to low-dose radiation.
      Unrepaired low-dose radiation damage to DNA is negligible compared to metabolic
      damage. The DNA damage-control biosystem is physiologically operative on both
      metabolic and radiation damage and effected predominantly by free radicals. The
      DNA damage-control biosystem is suppressed by high dose and stimulated by low
      dose radiation. The hormetic effect of low-dose radiation may be explained by its
      increase of biosystem efficiency. Improved DNA damage control reduces persistent
      mis- or unrepaired DNA damage i.e., the number of mutations that accumulate
      during a lifetime. This progressive accumulation of gene mutations in stem cells
      is associated with decreasing DNA damage control, aging, and malignancy.
      Recognition of the positive health effects produced by adaptive responses to low
      dose radiation would result in a realistic assessment of the environmental risk
      of radiation.

PMID- 9539033
TI  - Biological effects of low-level exposures: a perspective from U.S. EPA
      scientists.
AB  - Biological effects of low-level exposures (BELLE) may be very important in
      characterizing the potential health risks of environmental pollutants. Before
      some features of BELLE, such as effects that may be modulated by adaptive or
      defense mechanisms, can be taken into greater consideration in U.S. Environmental
      Protection Agency risk assessments, however adequate information on a toxicant's
      mode of action and answers to other questions are needed.

PMID- 9539032
TI  - Public health implications of environmental exposures.
AB  - The Agency for Toxic Substances and Disease Registry (ATSDR) is a public health
      agency with responsibility for assessing the public health implications
      associated with uncontrolled releases of hazardous substances into the
      environment. The biological effects of low-level exposures are a primary concern
      in these assessments. One of the tools used by the agency for this purpose is the
      risk assessment paradigm originally outlined and described by the National
      Academy of Science in 1983. Because of its design and inherent concepts, risk
      assessment has been variously employed by a number of environmental and public
      health agencies and programs as a means to organize information, as a decision
      support tool, and as a working hypothesis for biologically based inference and
      extrapolation. Risk assessment has also been the subject of significant critical
      review. The ATSDR recognizes the utility of both the qualitative and quantitative
      conclusions provided by traditional risk assessment, but the agency uses such
      estimates only in the broader context of professional judgment, internal and
      external peer review, and extensive public review and comment. This multifaceted
      approach is consistent with the Council on Environmental Quality's description
      and use of risk analysis as an organizing construct based on sound biomedical and
      other scientific judgment in concert with risk assessment to define plausible
      exposure ranges of concern rather than a single numerical estimate that may
      convey an artificial sense of precision. In this approach biomedical opinion,
      host factors, mechanistic interpretation, molecular epidemiology, and actual
      exposure conditions are all critically important in evaluating the significance
      of environmental exposure to hazardous substances. As such, the ATSDR risk
      analysis approach is a multidimensional endeavor encompassing not only the
      components of risk assessment but also the principles of biomedical judgment,
      risk management, and risk communication. Within this framework of risk analysis,
      the ATSDR may rely on one or more of a number of interrelated principles and
      approaches to screen, organize information, set priorities, make decisions, and
      define future research needs and directions.

PMID- 9539034
TI  - Low-level exposures: some implications for the U.S. Department of Energy.
AB  - The U.S. Department of Energy (U.S. DOE) maintains several programs to study and
      understand the health and environmental effects of exposure to low levels of
      energy-related agents. These programs include research to understand the
      mechanisms of action of agents of concern and to assess the risks associated with
      exposures of people and ecological systems to these agents. They also include
      implementing appropriate occupational safety and health standards and remediating
      waste sites to environmental standards. These programs require that the U.S. DOE
      pursue a realistic understanding of the effects of exposures to small amounts of
      energy-related agents. The largest of these programs involves hazardous waste
      remediation and includes potentially harmful exposures to low levels of numerous
      agents. The U.S. DOE conducts research to establish the scientific bases for the
      realistic assessment of risks of exposure to such wastes. As part of the U.S. DOE
      efforts to understand the risks of low-level exposures to hazardous waste, the
      Office of Health and Environmental Research and the Office of Environmental
      Management recently launched a broad cooperative program. It is comprised of
      research projects in nine general scientific areas and includes research on the
      health impacts and risk estimation of exposure to low levels of hazardous wastes.
      Projects for this new cooperative research program were selected from 610
      applications and totaled approximately $47 million in fiscal year 1996. This
      program marks a new approach by using basic research to reduce cleanup costs and
      to develop scientific foundations for advances in environmental technologies. The
      research will also examine the effects of exposure to low levels of chemical and
      radiological wastes.

PMID- 9539035
TI  - Risk assessment of low-level chemical exposures from consumer products under the
      U.S. Consumer Product Safety Commission chronic hazard guidelines.
AB  - The U.S. Consumer Product Safety Commission (CPSC) is an independent regulatory
      agency that was created in 1973. The CPSC has jurisdiction over more the 15,000
      types of consumer products used in and around the home or by children, except
      items such as food, drugs, cosmetics, medical devices, pesticides, certain
      radioactive materials, products that emit radiation (e.g., microwave ovens), and
      automobiles. The CPSC has investigated many low-level exposures from consumer
      products, including formaldehyde emissions from urea-formaldehyde foam insulation
      and pressed wood products, CO and NO2 emmissions from combustion appliances, and
      dioxin in paper products. Many chemical hazards are addressed under the Federal
      Hazardous Substances Act (FHSA), which applies to acute and chronic health
      effects resulting from high- or low-level exposures. In 1992 the Commission
      issued guidelines for assessing chronic hazards under the FHSA, including
      carcinogenicity, neurotoxicity, reproductive/developmental toxicity, exposure,
      bioavailability, risk assessment, and acceptable risk. The chronic hazard
      guidelines describe a series of default assumptions, which are used in the
      absence of evidence to the contrary. However, the guidelines are intended to be
      sufficiently flexible to incorporate the latest scientific information. The use
      of alternative procedures is permissible, on a case-by-case basis, provided that
      the procedures used are scientifically defensible and supported by appropriate
      data. The application of the chronic hazard guidelines in assessing the risks
      from low-level exposures is discussed.

PMID- 9539036
TI  - U.S. Food and Drug Administration perspective of the inclusion of effects of low
      level exposures in safety and risk assessment.
AB  - A brief overview is provided of some of the general safety and risk assessment
      procedures used by the different centers of the U.S. Food and Drug Administration
      (U.S. FDA) to evaluate low-level exposures. The U.S. FDA protects public health
      by regulating a wide variety of consumer products including foods, human and
      animal drugs, biologics, and medical devices under the federal Food, Drug, and
      Cosmetic Act. The diverse legal and regulatory standards in the act allow for the
      consideration of benefits for some products (e.g., drugs) but preclude them from
      others (e.g., food additives). When not precluded by statutory mandates (e.g.,
      Delaney prohibition), the U.S. FDA considers both physiologic adaptive responses
      and beneficial effects. For the basic safety assessment paradigm as presently
      used, for example in the premarket approval of food additives, the emphasis is on
      the identification of adverse effects and no observed adverse effect level(s)
      (NOAEL). Generally, the NOAEL is divided by safety factors to establish an
      acceptable exposure level. This safety assessment paradigm does not preclude the
      consideration of effects whether they are biologically adaptive or beneficial at
      lower dose levels. The flexibility to consider issues such as mechanisms of
      action and adaptive and beneficial responses depends on the product under
      consideration. For carcinogenic contaminants and radiation from medical devices,
      the U.S. FDA considers the potential cancer risk at low exposure levels. This
      generally involves downward extrapolation from the observed dose-response range.
      The consideration of adverse effects of other toxicologic end points (e.g.,
      reproductive, immunologic, neurologic, developmental) associated with low
      exposure levels is also becoming more of a reality (e.g., endocrine disrupters).
      The evaluation of the biologic effects of low-level exposures to toxic substances
      must include whether the effect is adverse or a normal physiologic adaptive
      response and also determine the resiliency of a physiologic system. The public
      health mandate of the U.S. FDA includes an active research program at the
      National Center for Toxicological Research and the other U.S. FDA centers to
      support the regulatory mission of the U.S. FDA. This includes the development of
      knowledge bases, predictive strategies, and toxicologic studies to investigate
      effects at the lower end of the dose-response range. Because of the wide
      diversity of legal and regulatory standards for various products regulated by the
      U.S. FDA agency-wide safety and risk assessment procedures and policies generally
      do not exist.

PMID- 9539037
TI  - Race and the delivery of care.

PMID- 9539038
TI  - Race and the delivery of care.

PMID- 9539039
TI  - Race and the delivery of care.

PMID- 9539040
TI  - Human rights, not enough.

PMID- 9539042
TI  - Medicine & the pursuit of wealth.

PMID- 9539041
TI  - Seeking harmony in discord.

PMID- 9539043
TI  - Confronting death. Who chooses, who controls? A dialogue between Dax Cowart and
      Robert Burt.

PMID- 9539044
TI  - Is better always good? The Enhancement Project.

PMID- 9539045
TI  - When comes "the end of the day?" A comment on the dialogue between Dax Cowart and
      Robert Burt.

PMID- 9539047
TI  - Punishing mothers.

PMID- 9539046
TI  - An alert and incompetent self. The irrelevance of advance directives.

PMID- 9539048
TI  - Health: a comprehensive concept.

PMID- 9539049
TI  - [Are there critical periods in child language development?].

PMID- 9539050
TI  - [Cochlear implants: a success story and some questions].

PMID- 9539051
TI  - [Guidelines/algorithms. The German Society of Otorhinolaryngology, Head and Neck
      Surgery].

PMID- 9539052
TI  - [Cochlear implants. Prosthetic management of deafness at the turn of the
      century].
AB  - In recent years the cochlear implant has become an established method for
      rehabilitation of bilateral sensory deafness in adults and children.
      Intracochlear multichannel stimulation with sophisticated speech coding
      strategies has proved to be reliable and safe enough for use in adults as well as
      young children; thus, a few cochlear implant systems with different
      specifications are currently available. The differences in their hardware and
      software are discussed. Furthermore, the current indications for cochlear
      implants in patients whose hearing is severely impaired and important aspects of
      the preoperative evaluation are presented with special emphasis on difficult
      cases such as deformities, multihandicapped subjects and very young children. Our
      results after 12 years of experience and more than 700 implantations suggest that
      the most important prognostic factor is the duration of deafness.

PMID- 9539053
TI  - [Cold deformation elements for attaching an implantable hearing aid transducer to
      ear ossicles or perilymph].
AB  - Development and short-term implantation results of the Tubingen implantable
      hearing aid (TI = Tubingen implant) have been presented. The TI is designed for
      patients with sensorineural hearing loss due to a malfunction of the cochlear
      amplifier. This can be identified by the presence of positive recruitment and the
      absence of TEOAE (transitory evoked otoacoustic emissions). The Tubingen implant
      functions in two ways: it allows electronic amplification of the auditory signal
      and electromechanical signal transduction into a micromechanical vibratory
      stimulus. There are two paths by which vibratory stimulus reaches the cochlea:
      (1) directly through a perforation in the stapes foot plate into the perilymph or
      (2) via the ossicular chain. Made of pure titanium, the casing of the helium
      tight welded transducer includes the piezoelectric actuator. An implantable
      manipulator device is designed for transducer positioning and anchoring in the
      mastoid cavity. Usually, the transducer probe tip is directly coupled to the body
      of the incus. This functions without a special coupling device by utilization of
      an Erbium-YAG laser. Special anatomical situations or the loss of incus and/or
      stapes suprastructure, however, requires coupling of the vibratory signal to
      other points of the ossicular chain or to the perilymph. A major problem,
      however, was an intraoperative, irreversible link between the titanium probe tip
      and coupling elements. To overcome this problem, the coupling elements were made
      of gold. A crimp technique was developed, allowing the surgeon to induce cold
      deformation of the gold. The cold deformation technique (crimp) results in an
      irreversible coupling between the titanium probe tip and the golden coupling
      element.

PMID- 9539054
TI  - [Magnetic resonance sialography. A new diagnostic method for imaging salivary
      duct patency].
AB  - The new technique of non-invasive magnetic resonance (MR) sialography was
      evaluated for normal and various pathologic conditions of the parotid gland. Ten
      volunteers and 15 patients with various symptomatic diseases of the parotid gland
      were tested in the present study. Diseases included pleomorphic adenoma,
      cystadenolymphoma, carcinoma ex pleomorphic adenoma, ductal carcinoma, adenoid
      cystic carcinoma, lymphoepithelial carcinoma, non-Hodgkin's lymphoma,
      sialolithiasis, sialadenitis, Heerfordt's syndrome and congenital duct ectasies.
      In addition to the usually performed T1 and T2 cross-sectional sequences a
      heavily weighted T2 sequence (TR 3600, TE 800) was performed and allowed
      depiction of a fluid-filled parotid duct. Results showed that the main parotid
      and primary branching ducts were depicted reliably in all normal cases and all
      patients, except one with sicca syndrome. Pathological conditions such as duct
      dilatations, duct strictures, obstructing duct calculus and irregular shapes and
      courses of the ductal system were demonstrable. While X-ray sialography obtained
      a higher resolution, only MR sialography was able to depict dilated ducts
      proximal from a complete obstruction, as well as all ductal cysts. Our findings
      show that MR sialography can be applied successfully to investigations of the
      parotid gland system. There have been no contraindications or complications to
      date because MR sialography is non-invasive. The technique will also allow the
      salivary ducts and lesions to be differentiated from the course of the facial
      nerve.

PMID- 9539055
TI  - [Comparative accuracy assessment between a mechanical (viewing wand) and a laser
      controlled microscopic positioning system using a geometric test model].
AB  - The precision of a new laser-guided navigation system (the "MKM") was compared
      with the "Viewing Wand" mechanical navigation system. We describe the inherent
      deviations in each positioning system as well as errors caused by data
      acquisition and referencing between the CT data set used for navigation and the
      original object. Two thousand individual measurements were performed on geometric
      test models scanned by CT. The technical accuracy of the mechanical navigation
      system varied between 0.48 mm in the most favorable area of the working field and
      1.8 mm in the more inaccurate areas. For the laser-guided system a precision of
      0.27 mm was found for all areas of the working field. After referencing between
      the CT data set and the original object, the error of measurement increased in
      both navigation systems: i.e., 0.83 mm for the Viewing Wand and 0.49 mm for the
      MKM system.

PMID- 9539056
TI  - [Pain therapy after tonsillectomy in adults].
AB  - The postoperative pain and stress experienced by tonsillectomy patients are often
      underestimated. For this reason traditional methods of analgesia are frequently
      used but with an ineffective result. Our study involved an analysis of pain
      sensation with regard to postoperative analgesia after adult tonsillectomies. In
      all, 150 patients following tonsillectomy were treated with different methods of
      analgesia, which included Diclofenac monotherapy and combined treatment with
      Tramadol-retard and Naproxen. Postoperative sensations of pain were realized in a
      visual analogous pain score, with consideration given to individual experiences
      of subjective pain. In addition, circulatory and hemopoiesis parameters were
      controlled. Results showed that the postoperative analgesic effect of Diclofenac
      was significantly less than that of Tramadol-retard and Naproxen. Diclofenac
      monotherapy after tonsillectomy was only sufficient in cases involving an
      individual's low pain sensation. In cases with moderate or stronger pain the
      tonsillectomy patient requires an effective postoperative analgesia, as achieved
      with combined therapy using Tramadol retard and Naproxen. Aggravating side
      effects were not found in both schemes of analgesia.

PMID- 9539057
TI  - [ACE-inhibitor-induced angioedema. The most frequent cause of oropharyngeal
      edema].
AB  - Angiotensin-converting enzyme (ACE) inhibitor-induced angioedema is supposed to
      be an uncommon cause for oropharyngeal edema. Between January 1, 1993 and
      February 1, 1997 we treated 20 patients with edema of the oropharyngeal region
      that was not caused by infection or irradiation. The most common reason was an
      ACE-inhibitor-induced angioedema and occurred in 9 cases, all of whom required
      inpatient treatment. The medical management consisted of the administration of
      intravenous (i.v.) glucocorticosteroids in all cases, H1-blockers in 6 cases,
      epinephrine by inhalation in one case and i.v. epinephrine in another case.
      Tracheostomy had to be performed in one patient. In our experience it is
      necessary to reconsider ACE inhibitor-induced angioedema in any case of an
      oropharyngeal edema. However, there is no reason for the routine application of
      epinephrine in these cases.

PMID- 9539058
TI  - [Anterior pseudodiverticulum after laryngectomy].
AB  - An anterior neopharyngeal pseudodiverticulum is a mucosal pouch located between
      the tongue and hypopharynx due to an epiglottis-like posterior tissue band that
      forms after total laryngectomy. This condition has rarely been mentioned in
      literature. Incidence, symptoms, treatment, and possible etiologic factors were
      examined. Twenty post-laryngectomy patients were questioned about swallowing
      disorders and were examined clinically and by barium swallow. Eleven patients
      were found to have a pseudodiverticulum, of which 9 patients suffered from
      dysphagia. We found no correlation between the formation of a pseudodiverticulum
      and radiotherapy or post-laryngectomy complications. All symptomatic patients
      were treated by dissecting the posterior tissue band endoscopically with a CO2
      laser, bringing complete relief of symptoms in 8 of 9 patients. Our study showed
      that the anterior pseudodiverticulum can be a frequent cause of dysphagia after
      laryngectomy. It can easily be diagnosed clinically and radiologically.
      Endoscopic treatment with a CO2-laser is simple and effective.

PMID- 9539059
TI  - [Air collection in the parotid region and the soft tissues of the neck
      bilaterally caused by self-insufflation].

PMID- 9539060
TI  - [Myoepithelial carcinoma (malignant myoepithelioma) of the salivary glands. A
      case report].
AB  - We report the rare development of a myoepithelial carcinoma in a pleomorphic
      adenoma involving the minor salivary glands in the buccal mucosa of a 78-year-old
      female. Tumor presented as a small asymptomatic left buccal mass. The initial
      dominant component of the neoplasm was a pleomorphic adenoma, while the minor
      component was a myoepithelial carcinoma. Recurrences of tumor after 2 and then 5
      years were excised. Histopathological examination of the last tissue removed
      showed a pure myoepithelial carcinoma of the minor salivary glands without
      evidence for a pleomorphic adenoma. The clinical features, therapy, diagnosis,
      histopathology and literature are reviewed.

PMID- 9539061
TI  - [Coincidence of isolated laryngeal sarcoidosis and laryngeal carcinoma].
AB  - Isolated sarcoidosis is quite rare, causing non-specific symptoms and possibly
      not diagnosed because of the large number of other entities with similar
      presentations. We report the problems of diagnosis of isolated laryngeal
      sarcoidosis following a localized carcinoma. A 66-year-old patient was seen in
      the Westpfalz ENT Department after a Le Roux-Robert fronto-latera laryngeal
      resection for a pT1a N0 M0 vocal cord carcinoma following progressue dyspnea.
      Laryngoscopy showed laryngeal stenosis due to a neoplastic lesion. However, an
      epitheloid granulomatosis was found on histopathology with no evidence for
      recurrent carcinoma. After exclusion of other processes and systemic disease, the
      diagnosis of isolated laryngeal sarcoidosis was made and long-term corticoid
      medication was administered, resulting in a rapid regression of the laryngeal
      stenosis.

PMID- 9539062
TI  - [Significance of the analysis of genetic alterations in head-neck carcinomas].

PMID- 9539063
TI  - Oxygen supply dependency in critical illness: an evolving understanding.

PMID- 9539064
TI  - Adrenal function and ruptured abdominal aortic aneurysm: keeping the hormones in
      check.

PMID- 9539065
TI  - From ventilator-induced lung injury to multiple organ dysfunction?

PMID- 9539066
TI  - Medical and ventilatory management of status asthmaticus.
AB  - Despite improved understanding of the basic mechanisms underlying asthma,
      morbidity and mortality remain high, especially in the "inner cities." The
      treatment of choice in status asthmaticus includes high doses of inhaled beta 2
      agonists, systemic corticosteroids, and supplemental oxygen. The roles of
      theophylline and anticholinergics remain controversial, although in general these
      agents appear to add little to the bronchodilator effect of inhaled beta-agonists
      in most patients. Anti-leukotriene medications have not yet been evaluated in
      acute asthma. Other therapies, such as magnesium sulfate and heliox, have their
      advocates but are not recommended as part of routine care. If pharmacological
      therapy does not reverse severe airflow obstruction in the asthmatic attack,
      mechanical ventilation may be temporarily required. Based on our current
      understanding of ventilator-induced lung injury, optimal ventilation of asthmatic
      patients avoids excessive lung inflation by limiting minute ventilation and
      prolonging expiratory time, despite consequent hypercapnia. Unless respiratory
      function is extremely unstable, the use of paralytic agents is discouraged
      because of the increased risk of intensive care myopathy. Patients who have
      suffered respiratory failure due to asthma are at increased risk for subsequent
      death due to asthma (14% mortality at 3 years) and should receive very close
      medical follow-up. In general, severe asthmatic attacks can best be prevented by
      early intervention in the outpatient setting. In the words of Dr. Thomas Petty,
      "... the best treatment of status asthmaticus is to treat it three days before it
      occurs".

PMID- 9539068
TI  - Adrenocortical function in patients with ruptured aneurysm of the abdominal
      aorta.
AB  - OBJECTIVE: To investigate adrenocortical function in patients with ruptured
      aneurysm of the abdominal aorta. DESIGN: Prospective clinical investigation.
      SETTING: Surgical intensive care unit in a university teaching hospital and
      intensive care unit in a general hospital. PATIENTS AND PARTICIPANTS: 54 patients
      with a documented rupture of the abdominal aorta. INTERVENTIONS: A short
      adrenocorticotrophic hormone (ACTH) stimulation test was performed. MEASUREMENTS
      AND RESULTS: Patients were studied within 24 h of admission to the hospital.
      Blood samples for the measurement of cortisol and ACTH were collected at 0800 h.
      Subsequently 0.25 mg tetracosactrin (Synacthen) was injected i.v. and after 60
      min cortisol measurement was repeated. The criterion for a normal short ACTH test
      was: stimulated or unstimulated cortisol levels > or = 0.55 mumol/l. For the
      group as a whole, an unstimulated plasma cortisol level of 0.76 mumol/l was
      comparable to that in other groups of critically ill patients with similar
      severity of illness. Between survivors and non survivors, significant differences
      were found between unstimulated plasma cortisol levels (0.70 vs 1.03 mumol/l),
      stimulated plasma cortisol levels (1.00 vs 1.30 mumol/l), and plasma ACTH levels
      (72 vs 133 ng/l). One patient did not meet the criteria for normal adrenocortical
      function: unstimulated plasma cortisol 0.26 mumol/l, stimulated plasma cortisol
      0.47 mumol/l. CONCLUSIONS: In the patients studied with ruptured aneurysm of the
      abdominal aorta, adrenocortical response was comparable to that in other groups
      of critically ill patients with similar severity of illness. High cortisol levels
      were associated with mortality. One patient did not meet the criteria for normal
      adrenocortical function but survival without steroid treatment.

PMID- 9539067
TI  - Oxygen supply dependency can characterize septic shock.
AB  - OBJECTIVE: To demonstrate that oxygen consumption (VO2) can be dependent on
      oxygen delivery (DO2) during hemodynamic instability and independent of DO2
      following stabilization. DESIGN: We retrospectively reviewed hemodynamic and
      blood gas data collected from ten patients in whom DO2 was acutely altered during
      an episode of septic shock (phase A) and after recovery from this episode (phase
      B). SETTING: General intensive care unit of a university hospital. PATIENTS: 10
      critically ill adult patients (aged 55 +/- 19 years). INTERVENTIONS: DO2 was
      altered by fluid challenge, administration of vasoactive agents, or application
      of positive end-expiratory pressure. RESULTS: In phase A, changes in VO2 (121 +/-
      32 vs 165 +/- 36 ml/min.m2; p < 0.001) paralleled changes in DO2 (415 +/- 153 vs
      607 +/- 217 ml/min.m2; p < 0.001), but oxygen extraction (O2ER) remained stable
      (31.9 +/- 11.2 vs. 30.2 +/- 8.9%; NS). In phase B, changes in DO2 (412 +/- 118 vs
      526 +/- 152 ml/min.m2; p < 0.001) were associated with opposite changes in O2ER
      (36.1 +/- 4.2 vs 28.9 +/- 4.9%; p < 0.001), and VO2 was unchanged (147 +/- 35 vs
      149 +/- 33 ml/min.m2; NS). The mean VO2/DO2 slope was greater in phase A than in
      phase B (0.26 +/- 0.09 vs. 0.08 +/- 0.08; p < 0.004). Blood lactate levels were
      higher in phase A than in phase B (3.3 +/- 1.8 vs 1.6 +/- 0.6 mEq/l; p < 0.05).
      CONCLUSIONS: Oxygen supply independency and dependency can be found at different
      times in the same critically ill patient. Our findings are consistent with the
      concept that VO2/DO2 dependency is a marker of septic shock. Interventions to
      increase DO2 are probably justified when this phenomenon is present.

PMID- 9539070
TI  - Acute effects of continuous rotational therapy on ventilation-perfusion
      inequality in lung injury.
AB  - OBJECTIVE: To investigate ventilation-perfusion (VA/Q) relationships, during
      continuous axial rotation and in the supine position, in patients with acute lung
      injury (ALI) using the multiple inert gas elimination technique. DESIGN:
      Prospective investigation. SETTING: Eighteen-bed intensive care unit in a
      university hospital. PATIENTS AND INTERVENTIONS: Ten patients with ALI (PaO2/FIO2
      ratio < 300 mm Hg) were mechanically ventilated in a pressure controlled mode and
      placed on a kinetic treatment table. MEASUREMENTS AND RESULTS: Distributions of
      VA/Q were determined 1) during rotation (after a period of 20 min) and 2) after a
      resting period of 20 min in the supine position. During axial rotation,
      intrapulmonary shunt (19.1 +/- 15% of cardiac output) was significantly reduced
      in comparison with when in the supine position (23 +/- 14%, p < 0.05), areas with
      "low" VA/Q were not affected by the positioning maneuver. General VA/Q mismatch
      (logarithmic distribution of pulmonary blood flow) was decreased during rotation
      (0.87 +/- 0.37) in comparison with when the patient was in the supine position
      (0.93 +/- 0.37, p < 0.05). Arterial oxygenation was significantly improved during
      continuous rotation (PaO2/FIO2 = 217 +/- 137 mm Hg) as compared with in the
      supine position (PaO2/FIO2 = 174 +/- 82 mm Hg, p < 0.05). The positive response
      of the continuous rotation on arterial oxygenation was only demonstrated in
      patients with a Murray Score of 2.5 or less, indicating a "mild to moderate" lung
      injury, while in patients presenting with progressive ARDS (Murray Score > 2.5),
      the acute positive response was limited. CONCLUSIONS: Continuous axial rotation
      might be a method for an acute reduction of VA/Q mismatch in patients with mild
      to moderate ALI, but this technique is not effective in late or progressive ARDS.
      Further studies including a large data collection are needed.

PMID- 9539069
TI  - Effects of human recombinant growth hormone (rhGH) on inflammatory responses in
      patients undergoing abdominal aortic aneurysm repair.
AB  - BACKGROUND: Human recombinant growth hormone (rhGH) has been shown to increase
      skeletal muscle protein synthesis and improve nitrogen balance in critically ill
      patients and those undergoing surgery. rhGH effects on hepatic protein turnover
      in critically ill patients are less clearly understood. OBJECTIVE: To examine
      rhGH effects on hepatic acute phase protein responses and inflammatory cytokine
      release in patients undergoing major surgery. DESIGN: Prospective double blind
      randomised trial. SETTING: Tertiary referral university teaching hospital.
      PATIENTS: Patients undergoing elective abdominal aortic aneurysm repair.
      INTERVENTION: Patients received rhGH (Genotropin, 0.3 IU/kg per day, n = 8) or
      placebo (n = 10) for 6 days prior to surgery. RESULTS: Blood levels of growth
      hormone (GH) and insulin-like growth factor (IGF-1) were measured following rhGH
      treatment and C-reactive protein (CRP), serum amyloid A (SAA) and the cytokines
      interleukin-6 (IL-6) and the IL-1 receptor antagonist (IL-1ra) were measured for
      up to 24 h following surgery. Significant increases in plasma rhGH (0.84 +/- 0.3,
      mean (sem) versus 52 +/- 20 mU/l, p < 0.0008) and IGF-1 levels (119 +/- 13 versus
      644 +/- 110 ng/ml, p < 0.0001) were seen prior to surgery following rhGH
      administration. No differences in acute phase protein or cytokine levels were
      seen following surgery in patients receiving rhGH. CONCLUSIONS: These results
      indicate that pre-operative administration of rhGH does not alter acute phase
      protein or inflammatory cytokine release in response to major surgery.

PMID- 9539071
TI  - A novel method of evaluation of three heat-moisture exchangers in six different
      ventilator settings.
AB  - OBJECTIVE: The purpose of this study was to assess and compare the
      humidification, heating, and resistance properties of three commercially
      available heat-moisture exchangers (HMEs). To mimic clinical conditions, a
      previously validated, new, realistic experimental set-up and measurement protocol
      was used. DESIGN: Prospective, comparative experimental study. SETTING: Surgical
      Intensive Care Unit, University Hospital of Rotterdam. MATERIALS: An experimental
      set-up consisting of a patient model, measurement systems, and ventilator and
      three different HME types. INTERVENTIONS: The air flow, pressure in the
      ventilation circuit, pressure difference over the HME, and partial water vapour
      pressure and temperature at each side of the HMEs were measured. Measurements
      were repeated every 30 min during the first 2 h and every hour up to 24 h for
      each HME at six different ventilator settings. The mean inspiratory and maximum
      expiratory resistance, flow-weighted mean absolute humidity and temperature
      outputs, and humidification and heating efficiencies of HMEs were calculated.
      MEASUREMENTS AND RESULTS: The Dar Hygroster had the highest humidity output,
      temperature output, humidification efficiency, and heating efficiency values
      throughout the study (32.8 +/- 21. mg/l, 32.2 +/- 0.8 degrees C, 86.3 +/- 2.3%,
      and 0.9 +/- 0.01%, respectively) in comparison to the Humid-Vent Filter (25.3 +/-
      3.2 mg/l, 31.9 +/- 0.8 degrees C, 72.2 +/- 5.3%, 0.9 +/- 0.02%, respectively) and
      the Pall Ultipor BB100 breathing circuit filter (23.4 +/- 3 mg/l, 28.3 +/- 0.7
      degrees C, 68.8 +/- 5.9%, 0.8 +/- 0.02%, respectively). The inspiratory and
      expiratory resistance of the HMEs remained below clinically acceptable maximum
      values (2.60 +/- 0.04 and 2.45 +/- 0.05 cmH2O/l per s, respectively). CONCLUSION:
      The Dar Hygroster filter was found to have the highest humidity and temperature
      output of all three HMEs, the Humid-Vent filter had a satisfactory humidity
      output only at low tidal volume flow rate and minute volume settings, whereas the
      Pall Ultipore BB 100 never achieved a sufficient humidity and temperature output.

PMID- 9539072
TI  - Volume replacement strategies on intensive care units: results from a postal
      survey.
AB  - OBJECTIVE: To assess volume replacement strategies on intensive care units (ICUs)
      in Germany. DESIGN: A postal survey questionnaire of 18 questions was sent to 451
      ICUs in Germany. The questionnaire was sent to general, surgical, anesthesiology,
      neurosurgery, cardiac surgery, and medical ICUs of hospital with more than 200
      beds. RESULTS: 286 questionnaires (64%) were returned and analysed.
      Hydroxyethylstarch (HES) solution is the solution most often used for volume
      replacement (total: 193 ICUs, exclusively HES: 93 ICUs), crystalloids are next
      (crystalloids exclusively: 61 ICUs), and human albumin is used rarely as a first
      choice. Clinical experience is a very important argument for administering
      volume. Diagnostic tools, e.g. measurement of central venous pressure or
      pulmonary capillary wedge pressure, also play an important role. Albumin/total
      protein and colloid osmotic pressure (COP) are measured often on ICUs (albumin
      measured routinely: 173 ICUs; COP measured routinely: 33 ICUs). Critical values
      for albumin/total protein are defined in most ICUs. Reduced plasma levels of
      albumin/total protein was the indication most often cited for administering human
      albumin. Only 149 ICUs (52%) have a financial budget for their unit. Costs still
      do not play a major role in the choice of volume replacement on 30 ICUs (10%).
      CONCLUSIONS: The kind of volume therapy differs widely among the different ICUs.
      This questionnaire supported the supposition that no standards exist for volume
      therapy in intensive care patients. New results concerning the abuse of albumin
      in the critically ill have not yet influenced strategies of volume replacement.

PMID- 9539073
TI  - Alternations of surface antigens on leukocytes after severe injury: correlation
      with infectious complications.
AB  - OBJECTIVE: To investigate the alternations of surface antigens of leukocytes
      after severe injury and the correlation with clinical outcome. SETTING: Emergency
      Department and Intensive Care Unit of a university hospital. PATIENTS: Patients
      with severe trauma (injury severity score > 16) were enrolled. Those who were
      transferred or had critical injuries were excluded. MEASUREMENTS AND RESULTS:
      Polymorphonuclear cells (PMN) and mononuclear cells (MN) were isolated from
      patients on the 1st, 3rd and 7th day following injury. The mean fluorescent
      expressions of CD11b and CD16 of PMN, and CD25 of MN were measured and compared
      with those obtained from paralleled controls. Sixteen injured patients were
      included. The CD11b expressions of PMN increased on the 1st day and were still
      high on the 7th day. The CD16 expressions decreased on the 1st day and CD25
      decreased on the 3rd day; both were still low on the 7th day. Six patients
      developed infectious complications. CD11b expression remained high and CD16
      expression remained low on three measurements of the infectious patients, whereas
      both expressions recovered on the last measurement of non-infectious patients.
      CD25 expression remained low in both groups. Three infectious patients with
      pneumonia died from multiple organ failure. CONCLUSIONS: Phenotypic alternations
      of leukocytes develop early after severe injury. The alternations may represent a
      state of activation of PMN and subsequent suppression of IL-2 related immunity.
      Persistent activation of PMN with enhanced CD11b and attenuated CD16 expression
      indicates the development of infectious complications and a poor prognosis can be
      anticipated if the infectious sites can not be controlled early.

PMID- 9539074
TI  - A normal platelet count at admission in acute meningococcal disease does not
      exclude a fulminant course.
AB  - OBJECTIVE: To determine the value of the platelet count at admission for the
      assessment of the severity of disease in acute meningococcal infections. DESIGN:
      Retrospective and prospective, descriptive patient study. SETTING: University
      Hospital Intensive Care Unit (ICU). PATIENTS: All patients (n = 92) with acute
      meningococcal disease from 1985 to 1997, who arrived at the ICU within 12 h after
      hospital admission and had more than one platelet count during the first 12 h.
      MEASUREMENTS AND RESULTS: After admission, platelets dropped in 95% of the
      patients. At admission, 2/41 (5%) of the non-hypotensive patients and 13/51 (25%)
      of the hypotensive patients had platelets fewer than 100 x 10(9)/l. During the
      following 12 h, these percentages increased to 15% and 71%, respectively.
      Fatalities had, at admission, a median platelet count of 111 x 10(9)/l (range, 19
      302 x 10(9)/l), whereas the nadir, occurring at median 7.0 h (range, 1.3-12 h),
      was 31 x 10(9)/l (range, 12-67 x 10(9)/l). Plasma TNF, measured shortly after
      admission, correlated better with the platelet nadir (r = -0.65, p < 0.0001) than
      with the platelet count at admission. Similarly, serum lactate correlated better
      with the platelet nadir. CONCLUSIONS: As platelets drop after admission, the use
      of the platelet count at admission for the assessment of the prognosis in acute
      meningococcal disease may be misleading. Frequently repeated platelet counts are
      a better tool for evaluating the severity of disease.

PMID- 9539075
TI  - Foregoing life-sustaining treatment in an Israeli ICU.
AB  - OBJECTIVE: To determine whether physicians in Israel withhold and/or withdraw
      life-sustaining treatments. DESIGN: A prospective, descriptive study of
      consecutively admitted patients. Patients were prospectively evaluated for
      diagnoses, types and reasons for foregoing life-sustaining treatment, mortality
      and times from foregoing therapy until mortality. SETTING: A general intensive
      care unit of a university hospital in Israel. RESULTS: Foregoing life-sustaining
      treatment occurred in 52 (13.5%) of 385 patients admitted and 5 (1%) had
      cardiopulmonary resuscitation. Withholding therapy occurred in 48 patients. Four
      patients with brain death had all treatments withdrawn. No patient had
      antibiotics, nutrition or fluids withheld or withdrawn. Time from foregoing
      therapy until death was 2.9 +/- 0.6 days. Thirty-one of 48 (65%) patients who had
      therapy withheld died within 48 h. CONCLUSIONS: Withholding life-prolonging
      treatments is common in an Israeli intensive care unit whereas withdrawing
      therapy is limited to brain dead patients. Terminal patients die soon after
      withholding, even if the therapy is not withdrawn. Withholding treatments should
      be an option for patients and professionals who object to withdrawing therapies.

PMID- 9539076
TI  - An evaluation of Patient Data Management Systems in Dutch intensive care.
AB  - OBJECTIVE: To assess the agreement between the functions of seven configurations
      of Patient Data Management Systems (PDMS) and the Dutch specifications prepared
      by the users prior to use. DESIGN: An observational descriptive study with
      hospital visits of seven configurations of five different PDMS systems including
      three commercial systems and two locally developed systems. SETTING: Seven Dutch
      level I intensive care units in university and teaching hospitals. MEASUREMENTS
      AND RESULTS: A substantial disagreement was found between the Dutch
      specifications and the actual functions of the PDMS configurations tested.
      Between the PDMS configurations, major differences in key features, including
      "automated charting", "information and care planning", and "management
      information", were observed. Automated charting is adequately supported by the
      three commercial systems. All configurations tested had limited functions
      supporting care planning. In none of the configurations tested was the required
      function present to support unit management with reports on resource utilisation
      and outcome performance. The automatic calculation of prognostic scores was
      either absent or incorrect. The implementation, the (continuous) configuration
      and the training required a substantial investment in costs and human resources.
      CONCLUSION: Today, none of the PDMSs tested satisfy the Dutch specifications.
      This can be explained by technical impossibilities of the systems and
      shortcomings in the actual configuration or in the unit organisation. The PDMS
      might become a valuable tool in improving the quality of ICU practice, but full
      implementation of these systems according to the specifications still has a long
      way to go.

PMID- 9539077
TI  - Lung overinflation without positive end-expiratory pressure promotes bacteremia
      after experimental Klebsiella pneumoniae inoculation.
AB  - OBJECTIVE: To determine the effect of peak inspiratory pressure (PIP) and
      positive end-expiratory pressure (PEEP) on the development of bacteremia with
      Klebsiella pneumoniae after mechanical ventilation of intratracheally inoculated
      rats. DESIGN: Prospective, randomized, animal study. SETTING: Experimental
      intensive care unit of a University. SUBJECTS: Eighty male Sprague Dawley rats.
      INTERVENTIONS: Intratracheal inoculation with 100 microliters of saline
      containing 3.5-5.0 x 10(5) colony forming units (CFUs) K. pneumoniae/ml. Pressure
      controlled ventilation (frequency 30 bpm; I/E ratio = 1:2; FIO2 = 1.0) for 180
      min at the following settings (PIP/PEEP in cmH2O): 13/3 (n = 16); 13/0 (n = 16);
      30/10 (n = 16) and 30/0 (n = 16), starting 22 h after inoculation. Arterial blood
      samples were obtained and cultured before and 180 min after mechanical
      ventilation and immediately before sacrifice in two groups of non-ventilated
      control animals (n = 8 per group). After sacrifice, the lungs were homogenized to
      determine the number of CFUs K. pneumoniae. MEASUREMENTS AND RESULTS: The number
      of CFUs recovered from the lungs was comparable in all experimental groups. After
      180 min, 11 animals had positive blood cultures for K. pneumoniae in group 30/0,
      whereas only 2, 0 and 2 animals were positive in 13/3, 13/0 and 30/10,
      respectively (p < 0.05 group 30/0 versus all other groups). CONCLUSIONS: These
      data show that 3 h of mechanical ventilation with a PIP of 30 cmH2O without PEEP
      in rats promotes bacteremia with K. pneumoniae. The use of 10 cmH2O PEEP at such
      PIP reduces ventilation-induced K. pneumoniae bacteremia.

PMID- 9539078
TI  - The effect of dobutamine on distal colon ischaemia in the pig.
AB  - OBJECTIVE: To test the hypotheses that dobutamine increases intestinal blood
      flow, it reduces mucosal acidosis and it prevents mucosal injury in an
      experimental porcine model of distal colonic ischaemia. And the hypothesis that
      mannitol prevents reperfusion injury. DESIGN: Randomised animal experiment.
      SETTING: University Hospital, Department of Experimental Research. MATERIALS:
      Twenty-four pigs. INTERVENTIONS: Twenty-one pigs were subjected to 7 h of
      controlled non-occlusive intestinal ischaemia of the distal colon, consisting of
      an occlusion of the inferior mesenteric artery (IMA) and a constriction of the
      superior mesenteric artery (SMA). At 3.5 h six pigs were treated with dobutamine,
      six with mannitol (0.18 g/kgBW), six with dobutamine and mannitol and three
      served as controls. Three non-ischaemic pigs were treated with dobutamine.
      MEASUREMENTS AND RESULTS: All animals were haemodynamically stable throughout the
      experiment. There was no difference in any variable between the animals treated
      with mannitol and those not treated. The ischaemic dobutamine-treated animals
      increased their cardiac output (CO) by 14% compared to baseline and by 59%
      compared to controls. The median final dosage of dobutamine was 13.2
      micrograms/kg per min (range 8.6-25.8). The blood flow in the restricted SMA, the
      intramucosal pH of the colonic mucosa (pHi) and the degree of histological
      mucosal injury were identical in animals treated with dobutamine and controls.
      The pH gap (pHa-pHi) correlated well (r = 0.97) with the PCO2 gap (aPCO2
      intestinal PCO2). The non-ischaemic animals treated with dobutamine increased CO
      by 37% and blood flow of the SMA by 16%. CONCLUSIONS: Dobutamine increased CO but
      did not ameliorate or deteriorate colonic ischaemia in this experimental model.
      The PCO2 gap correlated well with the pH gap.

PMID- 9539080
TI  - Severe community acquired pneumonia due to Staphylococcus aureus.

PMID- 9539079
TI  - Procalcitonin and C-reactive protein during the early posttraumatic systemic
      inflammatory response syndrome.
AB  - OBJECTIVES: To describe the initial evolution of serum procalcitonin (PCT) and C
      reactive protein (CRP) in previously healthy adult trauma patients and to compare
      the relationship of the expression of these two proteins with indicators of
      trauma severity. DESIGN: Prospective, descriptive, longitudinal study. SETTING:
      Surgical ICU in an university hospital. PATIENTS: Twenty-one patients admitted
      during the first posttraumatic 3 h exhibiting an Injury Severity Score (ISS)
      between 16 and 50 were enrolled. MEASUREMENTS: Blood sampling was performed on
      admission and on posttraumatic days 0.5, 1, 2 and 3 to assess serum levels of PCT
      and CRP. Total creatine kinase (CKtot) and lactate dehydrogenase (LDHtot)
      activities in the serum were used as tissue damage indicators. RESULTS: PCT
      exhibited an early and transient increase in serum levels similar to a more
      delayed change of CRP levels. Peak PCT and peak CRP were related to the ISS, the
      extent of tissue damage and the amount of fluid replacement during the first day.
      During the first 3 posttraumatic days, 90% of the patients exhibited a
      generalized inflammatory syndrome without infection. CONCLUSIONS: An early and
      transient release of PCT into the circulation was observed after severe trauma
      and the amount of circulating PCT seemed proportional to the severity of tissue
      injury and hypovolemia, yet unrelated to infection. The predictive value of both
      PCT and CRP for a forthcoming multiple organ failure still remains to be
      clarified.

PMID- 9539082
TI  - Horner's syndrome following internal jugular vein cannulation.
AB  - We present two cases of Horner's syndrome occurring following uncomplicated
      internal jugular venous cannulation. An awareness of this potential complication
      will reduce confusion over the aetiology of anisocoria in critically ill
      patients. This consideration is important, since lesions in the central nervous
      system or carotid dissection following trauma might otherwise be suspected.

PMID- 9539081
TI  - Group A streptococcal toxic shock syndrome with severe necrotizing fasciitis
      following hysterectomy--a case report.
AB  - In the last 10 years an increasing number of cases of group A streptococcal toxic
      shock syndrome have appeared in various clinical settings. The manifestation of
      this syndrome includes rapidly progressive multiorgan failure and soft-tissue
      necrosis. This report presents a case of streptococcal toxic shock syndrome
      caused by Streptococcus pyogenes with severe necrotizing fasciitis of the
      abdominal wall following hysterectomy. Aggressive surgical intervention with
      debridement of all necrotic tissue necessitated resection of the complete
      abdominal wall (skin, subcutaneous tissue, muscle and peritoneum). The abdominal
      wall defect was covered with free myocutaneous flaps and split-skin grafts.
      Optimal treatment, including adequate antibiotic therapy and radical surgical
      intervention, is an indispensable prerequisite of successful outcome.

PMID- 9539083
TI  - Accidental single brachial artery puncture leading to reversible ischaemia of the
      upper limb.

PMID- 9539084
TI  - Survival with extreme hypernatremia at 209 mmol/l.

PMID- 9539085
TI  - On acute poisoning with amphetamines.

PMID- 9539086
TI  - Cell adhesion molecules in clinical renal transplantation.
AB  - Leukocyte adhesion molecules are critically involved at a number of stages in
      immune and inflammatory responses, and their importance in the response to a
      renal allograft has been recognized for some years. They are involved in antigen
      presentation, in the cascade of events leading to extravasation of leukocytes
      into the allograft, in the subsequent migration of leukocytes through the
      extracellular matrix, and in the interactions between effector and target cells.
      Thus the adhesion molecules are highly attractive targets for therapeutic
      intervention in organ transplantation. Strategies have been explored to exploit
      the involvement of adhesion molecules in ischemia/reperfusion injury, allograft
      rejection, and the induction of immunological tolerance. Furthermore, the
      expression of a number of adhesion molecules is regulated by cytokines, and
      elevated levels may be detected both in transplant biopsies and as soluble forms
      measured in serum and urine. It has been proposed that these changes in levels
      might provide useful information in the diagnosis of allograft rejection and
      differentiation from other causes of graft dysfunction.

PMID- 9539087
TI  - The extracellular matrix: an early target of preservation/reperfusion injury and
      acute rejection after small bowel transplantation.
AB  - BACKGROUND: Endothelial cells are known to be an early target of
      preservation/reperfusion injury and acute rejection, whereas the extracellular
      matrix (ECM) may also play an equally important role in the sequelae of both
      events. METHODS: Syngeneic and allogeneic rat small bowel transplantations (SBTX)
      were performed after 6 hr of preservation. Animals were subsequently killed at
      defined time points for determination of ECM parameters within the graft and in
      plasma. RESULTS: Laminin levels were significantly increased 20 min after
      reperfusion (syngeneic SBTX: 357+/-65.9 ng/ml; allogeneic SBTX: 361+/-79.6 ng/ml;
      P< or =0.01). After syngeneic transplantation, laminin levels normalized by
      postoperative day (POD) 7, whereas there was a rejection-induced increase after
      allogeneic SBTX (POD 7: 179+/-60.1 ng/ml; POD 9: 333+/-13.6 ng/ml; P< or =0.01
      vs. syngeneic SBTX). This increase was accompanied by an increase in tumor
      necrosis factor-alpha levels at POD 9. Hyaluronic acid levels were significantly
      elevated after 24 hr (syngeneic SBTX: 1086+/-176 microg/L; allogeneic SBTX: 918+/
      108 microg/L; P< or =0.01). After syngeneic SBTX, hyaluronic acid levels
      normalized by POD 7, whereas persistently higher levels were observed after
      allogeneic SBTX. Immunohistochemistry confirmed early changes (20 min after
      reperfusion) at the ECM. Anti-laminin and anti-CD44 staining normalized at POD 5
      after syngeneic SBTX. After allogeneic SBTX, rejection-specific changes were
      evident with anti-laminin staining commencing on POD 5 and progressing until POD
      9. At similar time points, increased expression of fibronectin- and interferon
      gamma-positive material was evident. CONCLUSIONS: The ECM can be considered to be
      an early target of preservation/reperfusion injury and acute rejection. Plasma
      parameters reliably reflected the changes observed within the graft. Laminin and
      hyaluronic acid levels may be used as indicators of initial graft function.
      Furthermore, the increase in laminin levels was an early indicator of acute
      rejection. Determination of these parameters may significantly improve monitoring
      after SBTX.

PMID- 9539088
TI  - A significant reduction of macrophages expressing inducible nitric oxide synthase
      in rat hepatic allografts pretreated with donor-specific blood.
AB  - BACKGROUND: A single intravenous injection of donor-specific blood (DST) 7 days
      before transplantation significantly prolongs survival of hepatic allografts from
      fully allogeneic ACI(RT1a)-->LEW(RT1(1)) rats. The aim of this study was to
      investigate the kinetics of nitric oxide synthesis by macrophages in rat hepatic
      allografts treated with DST. METHODS: We investigated macrophages expressing
      inducible nitric oxide synthase in animal group I (receiving isografts), group II
      (hepatic allografts), and group III (hepatic allografts after donor-specific
      blood). RESULTS: Serum nitrite/nitrate, interferon-gamma, and tumor necrosis
      factor-alpha concentrations increased significantly in group II for 7 days after
      transplantation but were significantly much lower in groups I and III. Numbers of
      macrophages immunostained with an anti-macrophage nitric oxide synthase
      monoclonal antibody and inducible nitric oxide synthase mRNA levels in liver
      specimens also were much lower in groups I and III than in group II. In addition,
      Northern blot analysis demonstrated abundant interleukin-10 mRNA transcripts in
      the DST-treated hepatic allografts compared to untreated allografts. Double
      immunostaining revealed anti-macrophage synthase-containing cells, including both
      ED1+ and ED2+ cells, in liver and spleen as more numerous in group II.
      CONCLUSIONS: Inducible nitric oxide synthase is suppressed in immunologic
      unresponsiveness to grafts after donor-specific blood transfusion.

PMID- 9539090
TI  - Anti-inflammatory effect of transforming growth factor-beta1 in myoblast
      transplantation.
AB  - BACKGROUND: The inflammatory reaction that occurs during the 5 days after
      transplantation led at 3 days to the death of 70% of injected myoblasts. Use of
      anti-inflammatory agents appeared to be a possible way to increase myoblast
      survival. The application of gene transfer techniques to cell transplantation
      offers the potential for the prevention of inflammatory reaction. METHODS: In
      this study, transforming growth factor-beta1 (TGF-beta1) gene was introduced in
      myoblasts with a retroviral vector to permit the secretion of this anti
      inflammatory cytokine. Survival of (1) infected myoblasts expressing TGF-beta1 or
      (2) normal myoblasts transplanted with genetically modified cloned myoblasts was
      compared with survival of normal myoblasts. RESULTS: Expression of TGF-beta1 by
      myoblasts or by cotransplanted cells decreased myoblast mortality after 3 days by
      roughly 20% (66.0+/-3.0% in control vs. 46.3+/-4.2% and 46.2+/-5.9%). The
      increase of myoblast survival by TGF-beta1 expression was correlated with a lower
      polymorphonuclear cell and macrophage infiltration in muscles compared with
      control. In addition, cytotoxicity of neutrophils against myoblasts was assayed
      in vitro. The oxidation of myoblasts by activated neutrophils was decreased after
      infection of the myoblasts with the TGF-beta1 retroviral vector. CONCLUSIONS:
      These data demonstrate that the insertion of TGF-beta1 decreases inflammatory
      reaction observed after myoblast transplantation and thus prolongs their
      survival.

PMID- 9539089
TI  - Promiscuous recognition of major histocompatibility complex class II determinants
      in cyclosporine-induced syngeneic graft-versus-host disease: specificity of
      cytolytic effector T cells.
AB  - BACKGROUND: Administration of the immunosuppressive drug cyclosporine after
      syngeneic/autologous bone marrow transplantation paradoxically elicits a systemic
      autoimmune syndrome resembling graft-versus-host disease (GVHD). This syndrome,
      termed autologous or syngeneic GVHD, is associated with the development of a
      highly restricted repertoire of cytolytic T lymphocytes that promiscuously
      recognizes major histocompatibility complex class II determinants, including
      self. METHODS: Vbeta8.5+CD8+ effector lymphocytes and T-cell clones were isolated
      from Lewis rats with cylosporine-induced syngeneic GVHD. The specificity of the
      effector T cells and T-cell clones was examined in vitro. The pathogenicity of
      the T-cell clones was confirmed in vivo using a local graft-versus-host reaction
      assay. RESULTS: Clonal analysis reveals that the pathogenic effector T cells
      recognize a peptide from the invariant chain termed CLIP in association with
      major histocompatibility complex class II determinants. Moreover, there appears
      to be an additional interaction between the N-terminal flanking region of CLIP
      and the Vbeta segment of the T cell receptor. CONCLUSION: The results suggest
      that recognition of this highly conserved peptide along with the additional
      interaction between the flanking region and the T cell receptor may account for
      the promiscuous activity of the autologous/syngeneic GVHD autoreactive T cells.

PMID- 9539091
TI  - Possible relationship between heat shock protein 70, cardiac hemodynamics, and
      survival in the early period after heart transplantation.
AB  - BACKGROUND: Heat shock proteins (HSPs) are produced by cells in response to a
      wide variety of stresses. To determine a possible relationship between
      hemodynamic parameters and HSP 70 in the early postoperative period after heart
      transplantation, we examined immunohistochemically the inducible HSP 70 (anti-HSP
      72) response in human heart biopsies, as well as the effect of myocardial
      rejection on HSP. METHODS: A total of 105 routinely processed endomyocardial
      biopsies from 15 consecutive patients who underwent heart transplantation were
      examined. Analysis of hemodynamic and echocardiographic parameters were performed
      within 30 min and 12 hr after the biopsies. RESULTS: Immunohistochemically
      detected inducible HSP 70 was mainly located in the cytoplasm and
      nucleus/nucleolus of cardiomyocytes. Two specimens additionally showed HSP 70
      positive interstitial cells and smooth muscle cells of arteries, whereas
      lymphocytes were consistently negative. There was a significant relation between
      the echocardiographically determined increased relaxation time and positive HSP
      70 staining (P < 0.011). Patients with elevated right atrial pressure (P <
      0.098), as well as those with increased left ventricular end systolic diameter (P
      < 0.06), showed a trend to higher HSP expression. Three patients who died of
      sepsis or multiorgan failure showed significantly higher cytoplasmic HSP 70
      expression compared with 12 patients with stable clinical course. In case of
      rejection, significantly more patients showed no HSP expression. CONCLUSION:
      Although only five patients showed organ rejection, our results suggest an
      inverse relationship between HSP expression and rejection with the possibility of
      a role for HSP 70 as a graft marker to assess graft function.

PMID- 9539092
TI  - Apoptosis and increased expression of inducible nitric oxide synthase in human
      allograft rejection.
AB  - BACKGROUND: The mechanisms of myocyte death during cardiac allograft rejection
      are incompletely understood. In a previous study using a rat heterotopic cardiac
      allograft model, we showed that cardiac myocyte apoptosis, inducible nitric oxide
      synthase (iNOS) mRNA, protein and enzyme activity, and nitrotyrosine increased
      simultaneously during cardiac allograft rejection. This study was designed to
      investigate whether apoptosis and expression of iNOS occur in human cardiac
      allograft rejection. METHODS: Right ventricular endomyocardial biopsies from 30
      cases of allograft rejection (International Society of Heart and Lung
      Transplantation grade 3A/B) were compared with 12 biopsies with no rejection
      (International Society of Heart and Lung Transplantation grade 0). Samples were
      co-labeled for apoptosis and muscle actin. Serial sections were stained for iNOS,
      nitrotyrosine, and the leukocyte markers CD3, CD4, CD8, and CD68 to identify T
      cell subpopulations and macrophages. RESULTS: Biopsies with cardiac allograft
      rejection showed a 30-fold increase of apoptotic cells when compared with
      controls. Most apoptotic cardiac myocytes were found in proximity to macrophage
      (CD68+)-rich inflammatory infiltrates. iNOS immunoreactivity was strongest in
      macrophages and adjacent myocytes, which also showed high levels of
      nitrotyrosine, representing damage by peroxynitrite. CONCLUSIONS: Apoptosis is a
      major form of myocyte death during human cardiac allograft rejection. Cardiac
      myocyte apoptosis is closely associated with expression of iNOS in macrophages
      and myocytes and with nitration of myocyte proteins by peroxynitrite.

PMID- 9539093
TI  - Tacrolimus impairs wound healing: a possible role of decreased nitric oxide
      synthesis.
AB  - BACKGROUND: The effect of the immunosuppressant tacrolimus on wound healing is
      not known. Tacrolimus has been shown to decrease nitric oxide synthesis. The
      systemic inhibition of wound nitric oxide synthesis leads to impaired healing.
      METHODS: We studied the effect of systemic tacrolimus treatment on wound-breaking
      strength and collagen deposition 10 days after wounding in rats and to correlate
      the outcome of healing with wound nitric oxide synthesis. Beginning at the day of
      wounding, rats were treated once daily by intraperitoneal injections with 0.5,
      1.0, or 2.0 mg tacrolimus/kg body weight. Nitrite and nitrate were measured in
      wound fluid as an index of wound nitric oxide synthesis. Expression of inducible
      nitric oxide synthase in the wound was investigated by immunohistochemistry.
      Splenic lymphocytes were tested for proliferative activity. Tacrolimus levels in
      blood and wound fluid were measured by enzyme-linked immunosorbent assay.
      RESULTS: Systemic tacrolimus treatment was well tolerated by all rats. Tacrolimus
      accumulated in wound fluid. Tacrolimus levels in wound fluid were found to be
      approximately 10-fold higher than blood levels (P < 0.001). Tacrolimus (2.0
      mg/kg/day) reduced wound-breaking strength (P < 0.01) and collagen deposition (P
      < 0.05). This was paralleled by decreased wound nitrite + nitrate levels (P <
      0.001) and wound-inducible nitric oxide synthase expression. Splenic lymphocyte
      proliferative activity was significantly decreased by 1.0 and 2.0 mg
      tacrolimus/kg body weight/day (P < 0.05), indicating that the tacrolimus doses
      used were immunosuppressive. CONCLUSION: Our data show for the first time that
      tacrolimus impairs wound healing, and this is reflected by diminished wound
      nitric oxide synthesis.

PMID- 9539094
TI  - Cellular basis of skin allograft rejection in mice: specific lysis of allogeneic
      skin components by non-T cells.
AB  - BACKGROUND: It has been generally assumed that CD8+ T cells mediate direct lysis
      of allografts and that their growth, differentiation, and activation are
      dependent upon cytokine production by CD4+ T cells. However, both the generation
      of CD4- or CD8-deficient mice and adoptive transfer experiments with CD4+ T cells
      from CD8-deficient mice demonstrate that noncytotoxic CD4+ T cells alone are
      sufficient to induce skin or organ allograft rejection. Furthermore, we have
      reported that the major effector cells responsible for allografted-tumor (e.g.,
      Meth A) rejection are allograft-induced macrophages (AIM) with MHC haplotype
      specificity. METHODS: We characterized the macrophages migrating into the
      rejection site of allografted skin by immunohistochemical and in situ
      hybridization analyses using an antibody (K16.5) specific for AIM and a cDNA
      (pK30) encoding the antigen. To determine the in situ effector cells responsible
      for the rejection, we prepared both effector cells and target cells from the
      graft-graft bed border. RESULTS: The macrophages seemed to be morphologically
      (monocytic), phenotypically (K16.5+/pK30+), and functionally (cytotoxic against
      Meth A cells) AIM. The AIM population in bulk infiltrates taken from the
      rejection site was cytotoxic against allografted, but not self, skin components
      (e.g., fibroblasts, myocytes, endothelial cells, and epithelial cells). In
      contrast, other types of infiltrating cells including lymphocytes and
      granulocytes were virtually inactive toward these targets, and NK-1.1+ cells
      hardly infiltrated into the rejection site. CONCLUSIONS: These data suggest that
      the major effector cells mediating allografted skin rejection are AIM and not T
      cells.

PMID- 9539095
TI  - High-level endothelial expression of human CD59 prolongs heart function in an ex
      vivo model of xenograft rejection.
AB  - BACKGROUND: Hyperacute rejection of discordant xenografts is dependent on
      activation of the complement system of the recipient. Transgenic expression of
      recipient complement regulatory factors in donor tissue has proved to be a
      promising approach to dealing with hyperacute rejection, although the
      relationship between the level of complement regulatory factor expression and the
      degree of protection is not well established. Here, we examine this relationship
      using CD59 transgenic mouse hearts in an ex vivo model of xenograft rejection.
      METHODS: The level of expression of CD59 in two lines of transgenic mice, in
      which CD59 is expressed under the control of either the murine H2Kb (MHC class I)
      promoter (line CA-17) or the endothelium-specific human intercellular adhesion
      molecule-2 promoter (line 237-7), was compared by immunohistochemistry and flow
      cytometry. Hearts from both groups and wild-type controls were perfused ex vivo
      with human plasma, and mean heart work for each group was compared over a 60-min
      period. RESULTS: CD59 expression on cardiac endothelial cells isolated from
      homozygous CA-17 mice was 25- to 30-fold lower than that on cardiac endothelial
      cells from heterozygous 237-7 mice. CA-17 hearts perfused with 6% human plasma
      exhibited a reduction in deposition of the membrane attack complex, but not a
      prolongation of function, compared with nontransgenic mouse hearts. In contrast,
      237-7 hearts showed significantly prolonged function during perfusion with 20%
      plasma. CONCLUSIONS: High-level endothelial-specific expression of CD59 was
      effective in prolonging the function of mouse hearts perfused with 20% human
      plasma, whereas low-level, broader expression did not provide protection from 6%
      plasma.

PMID- 9539097
TI  - A crucial role of host CD80 and CD86 in rat cardiac xenograft rejection in mice.
AB  - BACKGROUND: Graft rejection can be initiated by two primary pathways of antigen
      presentation: (a) direct activation of host T cells by donor-derived antigen
      presenting cells (APC) and (b) indirect presentation of processed graft antigens
      by host APC. METHODS: We investigated the differential roles for direct and
      indirect antigen presentation by preventing the CD28 costimulatory pathway with
      monoclonal antibodies to rat or mouse CD80 and CD86 in a rat-to-mouse cardiac
      transplantation model. RESULTS: Although the mouse anti-rat monoclonal antibodies
      to CD80 and CD86 did not significantly prolong the survival of rat cardiac
      xenografts in mice, the rat anti-mouse monoclonal antibodies to CD80 and CD86 did
      prolong the survival. Development of the anti-donor antibodies was inhibited, and
      the deposition of C3, IgM, and IgG on endothelium in the xenografts was mild in
      the anti-mouse CD80/CD86-treated mice. Infiltration of macrophages, neutrophils,
      and lymphocytes expressing perforin and interferon-gamma was decreased by the
      anti-mouse CD80/CD86 treatment. CONCLUSIONS: These findings suggest that the
      indirect antigen presentation, which is mediated by CD80 and CD86 pathway on host
      APC, plays a crucial role in concordant cardiac xenograft rejection.

PMID- 9539096
TI  - Transgenic expression of human alpha1,2-fucosyltransferase (H-transferase)
      prolongs mouse heart survival in an ex vivo model of xenograft rejection.
AB  - BACKGROUND: The expression of human alpha1,2-fucosyltransferase (H-transferase,
      HT) has been proposed as an alternative strategy to alpha1,3
      galactosyltransferase (GT) gene knockout, which is not currently feasible in
      pigs, to reduce the galactose-alpha1,3-galactose (Gal) epitope expression. HT
      expression has recently been shown in transgenic mice and pigs to significantly
      reduce Gal expression on a variety of cells; however, its ability to do so on
      endothelial cells and its effectiveness at prolonging xenograft survival are yet
      to be determined. METHODS: HT-transgenic, Gal knockout (Gal KO) mice, and mice
      containing both genetic modifications (HT-transgenic/Gal KO) were tested for H
      substance and Gal expression on splenocytes and endothelial cells by flow
      cytometric analysis. In addition, the hearts of these mice were perfused ex vivo
      with 6% human plasma, and the effect on cardiac function was determined. RESULTS
      AND CONCLUSION: H-substance expression was detected on both splenocytes and
      endothelial cells of HT-transgenic mice. The level of H-substance expression was
      not affected by the presence or absence of GT in the cells, consistent with HT
      being dominant over GT. The ability of HT expression to reduce Gal expression was
      highly variable depending on the cell type. Gal expression on splenocytes was
      almost completely eliminated, whereas on endothelial cells, substantial Gal
      remained despite a 70% reduction. When perfused ex vivo with human plasma, hearts
      from HT-transgenic, Gal KO, and HT-transgenic/Gal KO mice demonstrated a similar
      prolongation in survival, compared with wild-type controls. Therefore, as far as
      hyperacute rejection is concerned, HT expression may be as effective as Gal KO in
      protecting against xenoantibody and complement mediated injury. However, the
      effect of residual Gal on non-hyperacute rejection responses remains to be
      determined.

PMID- 9539098
TI  - Alpha-galactosyl epitope-mediated activation of porcine aortic endothelial cells:
      type I activation.
AB  - BACKGROUND: The galactose alpha(1-3)galactose (alpha-gal) epitope associated with
      membrane glycoproteins and glycolipids represents a major determinant recognized
      on porcine cells by human xenoreactive natural antibodies (XNA). Together, bound
      XNA and complement rapidly induce porcine aortic endothelial cell (PAEC)
      activation; this process is associated with cellular shape changes, transient
      development of intercellular gaps, and loss of ATDPase and thrombomodulin, with
      release of heparan sulfate. The aim of this study was to evaluate patterns of
      type I endothelial cell activation (i.e., activation that does not require
      protein synthesis) following ligation of alpha-gal epitopes with anti-Gal
      antibodies and alpha-gal-specific lectins. METHODS AND RESULTS: PAEC incubated in
      the presence of the alpha-gal binding, Bandeiraea simplicifolia lectin (BS-I)
      underwent cellular shape changes associated with the formation of intercellular
      gaps. PAEC exposure to BS-I was also associated with the tyrosine phosphorylation
      of a protein (apparent molecular mass of approximately 130 kDa), not observed
      following lipopolysaccharide, tumor necrosis factor, or XNA stimulation. This
      lectin-induced tyrosine phosphorylation was not affected by cytochalasin D
      (inhibitor of actin filament polymerization), by genistein (inhibitor of tyrosine
      kinases), or by staurosporine (inhibitor of tyrosine phosphorylation and protein
      kinase C). In addition, incubation of PAEC with BS-I and monoclonal anti-Gal IgM
      induced p42/44 map kinase and activated the transcription factor NF-kappaB.
      CONCLUSIONS: Agonist binding of alpha-gal can evoke endothelial cell activation
      independently of complement activation. These observations have implications for
      the survival of xenografts.

PMID- 9539100
TI  - Tacrolimus and breastfeeding.

PMID- 9539099
TI  - Blockade of very late antigen-4 integrin binding to fibronectin in allograft
      recipients. II. Treatment with connecting segment-1 peptides prevents chronic
      rejection by attenuating arteriosclerotic development and suppressing intragraft
      T cell and macrophage activation.
AB  - BACKGROUND: Chronic rejection remains the leading obstacle to long-term allograft
      survival. We have shown that treatment of sensitized rats with rapamycin (RPM)
      does not prevent progressive chronic-type cardiac allograft failure. Having
      documented the role of fibronectin (FN) in the allograft rejection cascade, we
      hypothesized that treatment with synthetic peptides that specifically block
      adhesive interactions between the connecting segment-1 (CS1)-binding domain of FN
      and alpha4beta1 integrin on circulating cells may prevent the development of
      chronic rejection in transplant recipients. METHODS AND RESULTS: Lewis rats were
      sensitized with Brown Norway skin grafts (day -7), followed by transplantation of
      LBNF1 hearts (day 0). Experimental animals were treated with RPM (day -7 to -1;
      0.25 mg/kg/day i.p.), or RPM + CS1 peptides (day +7 to +13; 4 mg/kg/day i.v.),
      and euthanized at day 60. Unlike cardiac allografts in rats undergoing RPM
      monotherapy, those after adjunctive CS1 peptides had well preserved myocardial
      architecture and were free of arteriosclerotic lesions. Moreover, reverse
      transcription-polymerase chain reaction-based intragraft expression of
      transcripts for CD3, interferon-gamma, interleukin-12, monocyte chemoattractant
      protein-1, and transforming growth factor-beta were diminished in the CS1 group
      when compared with levels in the RPM group. The corresponding expression of
      cytokine proteins, as determined by immunoperoxidase labeling, was also depressed
      and correlated with decreased infiltration by T cells and macrophages.
      CONCLUSION: CS1 peptide-facilitated blockage of alpha4beta1-FN interactions
      prevents the development of chronic rejection and depresses the expression of key
      T cell- and macrophage-associated cytokines/chemoattractants. Hence, local
      synthesis of FN is an ongoing feature of, and adhesive FN-alpha4beta1
      associations are critical for, the development of chronic transplant rejection.

PMID- 9539101
TI  - Enhanced detection of human telomerase activity.
AB  - The detectability of telomerase activity in human cells almost always correlates
      with indefinite proliferation capability (immortalization). To make quantitative
      statements about telomerase activity levels, complete extraction of the
      telomerase activity is needed. A series of detergents was tested for this
      purpose, and a combination of NP-40 and sodium deoxycholate (NaDOC) was found to
      be the most efficient for extracting telomerase activity. Tumor-derived cell
      lines originally thought to contain differing amounts of telomerase on the basis
      of the original CHAPS bases extraction procedures have nearly equivalent amounts
      of activity when extracted with the NP-40/NaDOC lysis buffer. These results
      indicate that these lysis conditions can be used to extract telomerase activity
      more efficiently from tumor-derived cell lines.

PMID- 9539102
TI  - Human leukotriene B4 omega-hydroxylase (CYP4F3) gene: molecular cloning and
      chromosomal localization.
AB  - Leukotriene B4 (LTB4) omega-hydroxylase catalyzes the conversion of LTB4 into a
      biologically less active product, 20-hydroxy-LTB4. In a preceding paper (Kikuta
      et al., 1993), we showed human polymorphonuclear leukocyte (PMN) LTB4 omega
      hydroxylase to be a novel form of cytochrome P450, designated CYP4F3, on the
      basis of its cDNA cloning and expression in yeast cells. Here, we have isolated
      the gene encoding CYP4F3 and determined its genomic organization and chromosomal
      localization. The CYP4F3 gene contained 13 exons and spanned approximately 22.2
      kb. The cDNA of CYP4F3 contained 5050 nucleotides excluding the poly(A) tail. The
      translation initiation codon (ATG) was present in exon II. Primer extension and
      S1 mapping analyses indicated that the transcription initiation site is 49
      nucleotides upstream from the 3' end of exon I, and no other initiation sites
      were detected. A TATA-box-like sequence (TACAT) and 120-b GC-rich sequence were
      observed just before transcription initiation site. Several putative regulating
      elements recognized by the GATA family, MZF-1, CACCC binding protein, and C/EBP,
      were identified in its 5' flanking region. Genomic DNA screening for CYP4F3 and
      Southern blot analysis suggested the existence of other CYP4F genes in addition
      to CYP4F3 and CYP4F2 in the human genome. Fluorescence in situ hybridization
      demonstrated that the CYP4F3 gene is located at 19p13.2.

PMID- 9539103
TI  - Quantification of multiple human cytochrome P450 mRNA molecules using competitive
      reverse transcriptase-PCR.
AB  - We developed a quantitative competitive reverse transcriptase-polymerase chain
      reaction (QC RT-PCR) assay to measure mRNA levels of seven human cytochrome P450
      (P450, CYP) genes and microsomal epoxide hydrolase (EH) simultaneously. This
      assay employs an exogenous recombinant RNA (rcRNA) molecule as an internal
      standard that shares PCR primer and hybridization probe sequences with CYP1A1,
      CYP1A2, CYP2A6/7, CYP2D6, CYP2E1, CYP2F1, CYP3A4/5/7, and EH mRNA. Because each
      rcRNA molecule contains several primer sequences, an entire battery of genes that
      exhibit differential responsiveness to various classes of xenobiotics may be
      measured simultaneously from one population of cDNA molecules. In this study, we
      demonstrated the precision and power of the assay using small amounts of human
      liver total RNA. We also report for the first time quantitative profiles of P450
      and EH mRNA abundance in eight human livers. Cytochrome P450 2E1 mRNA maintained
      the highest abundance (average 6.67 x 10(7) molecules/microg of total RNA) and
      least variation (13 fold) in all livers examined. Cytochrome P450 1A2, CYP2A6/7,
      CYP2D6, CYP3A4/5, and EH mRNAs were approximately one order of magnitude less
      abundant than CYP2E1 transcripts, with CYP2D6 levels exhibiting the greatest
      variation (220 fold) between individuals. This QC RT-PCR assay should prove
      valuable for measuring basal and induced mRNAs in different cell types in vitro,
      as well as in biomonitoring applications where individuals are exposed or
      hypersusceptible to certain xenobiotic-initiated toxicities.

PMID- 9539104
TI  - A cell cycle regulating receptor is localized on cell surface and in nuclei of
      mitotically and meiotically dividing cells.
AB  - We previously showed that a heterodimeric surface receptor of molecular weight
      65,000 (p65) and 95,000 (p95) is expressed on the surface of proliferating cells
      such as activated T lymphocytes and neural precursors. This p65/p95 receptor is
      recognized by a monoclonal antibody and by type 3 reovirus hemagglutinin. Binding
      of the surface p65/p95 receptor leads to a growth arrest of mitotic cells and a
      consequent inhibition of proliferation. The p65/p95 receptor was demonstrated to
      be associated with kinase activity. Because p65/p95 is involved in the regulation
      of mitotic cell division, we sought to study the cellular distribution of the
      receptor and its possible role in meiotic cell division. Immunohistochemical
      labeling and flow cytometry studies were done using adult rat testes and cell
      lines. All cells undergoing mitotic or meiotic division in the rat testis
      expressed the p65/p95 receptor; cells that do not divide did not express
      receptors. Dividing cells had two receptor pools. As previously reported for
      several mitotically active tissues, a pool of receptors was localized on the cell
      surface. Interestingly, a pool of receptors was also seen intracellularly over
      the nucleus of labeled cells. The nuclear label seemed to be associated with
      chromosomes during specific stages of the mitotic and the two meiotic divisions,
      suggesting a role in the regulation of nuclear events. Further studies on this
      receptor and the function of the nuclear pool should provide a better
      understanding of the control of cell division.

PMID- 9539105
TI  - Expression and processing of G0/G1 switch gene 24 (G0S24/TIS11/TTP/NUP475) RNA in
      cultured human blood mononuclear cells.
AB  - The human G0/G1 switch (G0S) gene, G0S24, and its rodent immediate-early homolog
      (TIS11, TTP, NUP475) are part of a mammalian gene family whose members encode
      CCCH zinc finger domains and domains similar to part of the large subunit of RNA
      polymerase II and to the Mei2 regulator of G1 arrest in fission yeast. We
      compared the RNA expression of G0S24 with that of other G0S genes in cultured
      blood mononuclear cells and examined the levels of various RNA processing
      intermediates. Freshly isolated cells contained high levels of several G0S RNAs,
      which declined by 24 h, suggesting transient spontaneous stimulation during cell
      purification (Heximer et al., 1996). However, in cells preincubated for 24 h,
      G0S24 RNA levels remained much higher than those of other G0S genes (107+/-42 x
      10(6) molecules/microg of RNA); stimulation with lectin (Con-A) further increased
      G0S24 RNA, much of which remained nuclear. Like those of FOS/G0S7, EGR1/G0S30 and
      of the gene encoding the regulator of G protein signalling 1 (RGS1), G0S24 RNA
      levels increased more in response to a protein kinase C activator than to a
      calcium ionophore, whereas the opposite held for FOSB/G0S3 and RGS2/G0S8. With
      appropriate PCR primer pairs, we showed a G0S24 RNA processing intermediate,
      which crossed the exon-1/intron boundary, and nonpolyadenylated nuclear RNA
      extending into the 3' flank, where there is a second CpG island. The
      concentration of the latter intermediate (1.2+/-0.2 x 10(6) molecules/microg of
      RNA), which increased transiently on cell stimulation, did not account for all
      G0S24 nuclear RNA. The levels of G0S24 RNA and both intermediates were increased
      by the protein synthesis inhibitor cycloheximide, consistent with regulation by a
      labile repressor.

PMID- 9539106
TI  - Inhibition of epidermal growth factor-mediated ERK1/2 activation by in situ
      electroporation of nonpermeant [(alkylamino)methyl]acrylophenone derivatives.
AB  - The interruption of signaling cascades in intact cells through the introduction
      of nonpermeant compounds inferred by in vitro studies to specifically inhibit
      epidermal growth factor (EGF) receptor (EGF-R) function is described. Two
      nonpermeant [(alkylamino)methyl]acrylophenone derivatives,
      [(dimethylamino)methyl] acrylo-para-[(benzoylsulfonyl)-oxy]phenone and
      [(dimethylamino)-methyl]acrylo-para-[(hydroxy-benzoylsulfonyl++ +)-oxy]phenone,
      were introduced by in situ electroporation into mouse or rat fibroblasts growing
      on indium-tin oxide-coated glass. Cells were subsequently stimulated with growth
      factors and assessed for activation of a downstream target, the extracellular
      signal-regulated kinase (ERK1/2), by probing with specific antibodies. Electrodes
      and slides were configured to provide non-electroporated control cells side by
      side with the electroporated ones, both growing on the same type of indium-tin
      oxide-coated glass surface. Using this set-up, these compounds could inhibit EGF-
      but not platelet-derived growth factor (PDGF)-mediated ERK1/2 activation in vivo.
      These results demonstrate the potential of the in situ electroporation approach
      for the study of tyrosine kinase action using selective but nonpermeant
      inhibitors that would otherwise be ineffective in intact cells.

PMID- 9539107
TI  - Structure of 5' region of human tenascin-R gene and characterization of its
      promoter.
AB  - The tenascin-R (TN-R) gene encodes a multidomain extracellular matrix protein
      belonging to the tenascin family, previously detected only in the central nervous
      system. In this report, we describe the structure of the 5' region of the human
      TN-R gene and characterize the activity of its promoter. We cloned two previously
      unreported nontranslated exons (exons 1 and 2, 539 and 101 bp in length,
      respectively) separated by a large (> or = 40-kb) intron. The intron between
      exons 2 and 3 (containing the ATG codon) is 122 kb in length. Tenascin-R
      transcripts in fetal, adult, and neoplastic human brain contain both exons 1 and
      2, as demonstrated by S1 nuclease analysis and reverse transcriptase-polymerase
      chain reaction. The human TN-R promoter displays relatively unusual features in
      terms of sequence in that it lacks any TATA box, CAAT box, GC-rich regions, or
      initiator element. The promoter displays its activity only in cultured cells of
      neural and glial origin, not in transformed epithelial cells and melanoma cells.
      All the elements required for the full and cell-specific activity of the promoter
      are contained in the 57-bp sequence closest to the transcription startpoint.

PMID- 9539108
TI  - Structural characterization and tissue-specific expression of the mouse glucose-6
      phosphate dehydrogenase gene.
AB  - Glucose-6-phosphate dehydrogenase (G6PD) activity differs among tissues and, in
      liver, with the dietary state of the mouse. Tissue-specific differences in G6PD
      activity in adipose tissue, liver, kidney, and heart were associated with similar
      differences in the amount of G6PD mRNA. Regulation of mRNA amount by dietary fat
      was only observed in liver. In mice fed a low-fat diet, the relative amounts of
      G6PD mRNA were 3:1:1:0.38, respectively, in the four tissues. Further, the amount
      of precursor mRNA for G6PD in liver, kidney, and heart reflected the amount of
      mature mRNA in these tissues, suggesting differing transcriptional activity. Our
      S1 nuclease and primer-extension analyses indicated that the same transcriptional
      start site is used in liver, kidney, and adipose tissue, resulting in a common 5'
      end of the mRNA in these tissues. Thus, differential regulation is not
      attributable to alternate promoter usage. A DNase hypersensitivity analysis of
      the 5' end of the G6PD gene identified three hypersensitive sites (HS): HS 1 and
      HS 2 were present in all tissues, whereas HS 3 was liver specific. Thus,
      regulation of G6PD expression involves both dietary and tissue-specific signals
      that appear to act via different mechanisms.

PMID- 9539109
TI  - 307-bp fragment in HOXA7 upstream sequence is sufficient for anterior boundary
      formation.
AB  - The HOX genes are expressed in a positionally and temporally restricted manner
      involving anteroposterior axial pattern formation during early embryogenesis.
      Previously, we studied the sequence and function of an upstream regulatory region
      of the human HOXA7 gene. To identify a critical cis-acting element, a deletion
      analysis was performed along the human control region (HCR) (about 1.1 kb), which
      was sufficient for setting the anterior boundary of expression in transgenic
      mice. We demonstrated that a 307-bp control region contains a cis-acting
      element(s) specifying an anterior boundary as well as a dorsal-ventral
      restriction in the neural tube at day 12.5 postconception (p.c.). The distinct
      anterior limit of expression was noted at the level of C7/T1 in the neural tube
      and spinal ganglia. In addition, our deletion experiments revealed that the HCR
      consisted of several cis-acting elements which were individually capable of
      driving regionally restricted expression patterns in the neural tube and limb
      buds.

PMID- 9539110
TI  - Rat mitochondrial glycerol-3-phosphate dehydrogenase gene: multiple promoters,
      high levels in brown adipose tissue, and tissue-specific regulation by thyroid
      hormone.
AB  - Mitochondrial FAD-linked glycerol-3-phosphate dehydrogenase (mtGPDH) is one of
      the two enzymes of the glycerol phosphate shuttle. This shuttle transfers
      reducing equivalents from the cytoplasm to the mitochondria in a unidirectional,
      exothermic manner. Here, the isolation and characterization of the rat nuclear
      gene (Gpd2) encoding mtGPDH is reported. The mtGPDH gene spans 100 kb and
      consists of 17 exons. The use of alternate promoters was suggested by the
      presence of three different first exons and confirmed by transient expression for
      two of them. The first exons are expressed in a tissue-restricted manner. Exon 1a
      was found primarily in brain, exon 1b was used in all tissues examined, and exon
      1c was detected predominantly in testis. Depending on the tissue, different
      transcript lengths were also observed: 5.9 kb (all tissues), 3.6 kb (skeletal
      muscle), and 2.5 kb (testis). The length isoforms are attributable to alternate
      splicing and polyadenylation site use. Very high mtGPDH mRNA levels were found in
      brown adipose tissue, 75 fold greater than in white adipose tissue. Thyroid
      hormone increased mtGPDH mRNA levels in liver and heart but not in brown adipose
      tissue, brain, or testis. This pattern corresponds to that of thyroid hormone
      induced oxygen consumption and is consistent with a role for mtGPDH in thyroid
      hormone-induced thermogenesis. Both thyroid-responsive and nonresponsive tissues
      used promoter 1b, suggesting that tissue-specific factor(s) contribute to the
      tissue-restricted responsiveness to thyroid hormone.

PMID- 9539111
TI  - New perspectives on classical conditioning: a synthesis of Hebbian and non
      Hebbian mechanisms.

PMID- 9539113
TI  - Aberrant RNA splicing in sporadic amyotrophic lateral sclerosis.

PMID- 9539112
TI  - Does cerebellar LTD mediate motor learning? Toward a resolution without a smoking
      gun.

PMID- 9539114
TI  - Introduction: one decade of Neuron, six decades of neuroscience.

PMID- 9539115
TI  - Voltage-gated ion channels and electrical excitability.

PMID- 9539116
TI  - From muscle endplate to brain synapses: a short history of synapses and agonist
      activated ion channels.

PMID- 9539117
TI  - Vesicle pools and Ca2+ microdomains: new tools for understanding their roles in
      neurotransmitter release.

PMID- 9539118
TI  - Early exploration of the visual cortex.

PMID- 9539119
TI  - The emergence of modern neuroanatomy and developmental neurobiology.

PMID- 9539120
TI  - Molecular neurobiology and genetics: investigation of neural function and
      dysfunction.

PMID- 9539121
TI  - Cognitive neuroscience and the study of memory.

PMID- 9539122
TI  - neurogenin1 is essential for the determination of neuronal precursors for
      proximal cranial sensory ganglia.
AB  - The NEUROGENINS (NGNs) are neural-specific basic helix-loop-helix (bHLH)
      transcription factors. Mouse embryos lacking ngn1 fail to generate the proximal
      subset of cranial sensory neurons. ngn1 is required for the activation of a
      cascade of downstream bHLH factors, including NeuroD, MATH3, and NSCL1. ngn1 is
      expressed by placodal ectodermal cells and acts prior to neuroblast delamination.
      Moreover, NGN1 positively regulates the Delta homolog DLL1 and can be negatively
      regulated by Notch signaling. Thus, ngn1 functions similarly to the proneural
      genes in Drosophila. However, the initial pattern of ngn1 expression appears to
      be Notch independent. Taken together with the fact that ectopic ngn1 expression
      can convert ectodermal cells to neurons in Xenopus (Ma et al., 1996), these data
      and those of Fode et al. (1998 [this issue of Neuron]) identify ngns as
      vertebrate neuronal determination genes, analogous to myoD and myf5 in
      myogenesis.

PMID- 9539123
TI  - The bHLH protein NEUROGENIN 2 is a determination factor for epibranchial placode
      derived sensory neurons.
AB  - neurogenin2 encodes a neural-specific basic helix-loop-helix (bHLH) transcription
      factor related to the Drosophila proneural factor atonal. We show here that the
      murine ngn2 gene is essential for development of the epibranchial placode-derived
      cranial sensory ganglia. An ngn2 null mutation blocks the delamination of
      neuronal precursors from the placodes, the first morphological sign of
      differentiation in these lineages. Mutant placodal cells fail to express
      downstream bHLH differentiation factors and the Notch ligand Delta-like 1. These
      data suggest that ngn2 functions like the Drosophila proneural genes in the
      determination of neuronal fate in distal cranial ganglia. Interestingly, the
      homeobox gene Phox2a is activated independently of ngn2 in epibranchial placodes,
      suggesting that neuronal fate and neuronal subtype identity may be specified
      independently in cranial sensory ganglia.

PMID- 9539124
TI  - Expression of a protein kinase C inhibitor in Purkinje cells blocks cerebellar
      LTD and adaptation of the vestibulo-ocular reflex.
AB  - Cerebellar long-term depression (LTD) is a model system for neuronal information
      storage that has an absolute requirement for activation of protein kinase C
      (PKC). It has been claimed to underlie several forms of cerebellar motor
      learning. Previous studies using various knockout mice (mGluR1, GluRdelta2, glial
      fibrillary acidic protein) have supported this claim; however, this work has
      suffered from the limitations that the knockout technique lacks anatomical
      specificity and that functional compensation can occur via similar gene family
      members. To overcome these limitations, a transgenic mouse (called L7-PKCI) has
      been produced in which the pseudosubstrate PKC inhibitor, PKC[19-31], was
      selectively expressed in Purkinje cells under the control of the pcp-2(L7) gene
      promoter. Cultured Purkinje cells prepared from heterozygous or homozygous L7
      PKCI embryos showed a complete blockade of LTD induction. In addition, the
      compensatory eye movements of L7-PKCI mice were recorded during vestibular and
      visual stimulation. Whereas the absolute gain, phase, and latency values of the
      vestibulo-ocular reflex and optokinetic reflex of the L7-PKCI mice were normal,
      their ability to adapt their vestibulo-ocular reflex gain during visuo-vestibular
      training was absent. These data strongly support the hypothesis that activation
      of PKC in the Purkinje cell is necessary for cerebellar LTD induction, and that
      cerebellar LTD is required for a particular form of motor learning, adaptation of
      the vestibulo-ocular reflex.

PMID- 9539125
TI  - Mechanisms of direction selectivity in macaque V1.
AB  - Mechanisms underlying direction selectivity were studied in V1 of alert fixating
      macaque monkeys. Some direction-selective cells showed delayed asymmetric
      inhibition, some showed a shifting excitatory time course across the receptive
      field, and some showed both. Both the direction of the spatial offset of the
      inhibition and the direction of the shift in excitatory response time course
      correlated with the cells' preferred directionality. The delayed asymmetric
      inhibition may contribute to the shifting response time course. The data suggest
      that asymmetric inhibition is the major determinant for directionality in these
      cells, though both mechanisms could contribute. Based on this physiology, a
      simple, single-cell model is proposed, consistent with the known anatomy of some
      direction-selective cells.

PMID- 9539126
TI  - Mechanisms of concerted firing among retinal ganglion cells.
AB  - Nearby retinal ganglion cells often fire action potentials in near synchrony. We
      have investigated the circuit mechanisms that underlie these correlations by
      recording simultaneously from many ganglion cells in the salamander retina.
      During spontaneous activity in darkness, three types of correlations were
      distinguished: broad (firing synchrony within 40-100 ms), medium (10-50 ms), and
      narrow (<1 ms). When chemical synaptic transmission was blocked, the broad
      correlations disappeared, but the medium and narrow correlations persisted.
      Further analysis of the strength and time course of synchronous firing suggests
      that nearby ganglion cells share inputs from photoreceptors conveyed through
      interneurons via chemical synapses (broad correlations), share excitation from
      amacrine cells via electrical junctions (medium), and excite each other via
      electrical junctions (narrow). It appears that the firing patterns in the optic
      nerve are strongly shaped by electrical coupling in the inner retina.

PMID- 9539127
TI  - Networks of coactive neurons in developing layer 1.
AB  - Spontaneous neuronal activity plays an important role in the development of
      cortical circuitry, yet its spatio-temporal dynamics are poorly understood. Cajal
      Retzius (CR) neurons in developing layer 1 are necessary for correct cortical
      lamination and are strategically located to coordinate early circuit activity. To
      characterize the spontaneous activity of CR and other layer 1 neurons during
      cortical development, we imaged calcium transients in populations of layer 1
      neurons in hemispheres and slices from postnatal rat somato-sensory neocortex.
      The spontaneous activity in layer 1 had complex spatio-temporal patterns. Groups
      of non-CR cells showed synchronous activations and formed networks of correlated
      neurons superimposed in the same territory. Correlated activity among non-CR
      cells was mediated by a depolarizing effect of GABA and was modulated by
      glutamate, probably released by CR cells. Our findings demonstrate that
      developing layer 1 can sustain complex patterns of correlated activity and reveal
      a circuit mechanism that can mediate this patterned activity.

PMID- 9539128
TI  - Periodicity of thalamic synchronized oscillations: the role of Ca2+-mediated
      upregulation of Ih.
AB  - Thalamocortical networks can generate both normal and abnormal patterns of
      synchronized network activity, such as spindle waves and spike-and-wave seizures.
      These periods of synchronized discharge are often separated by a silent,
      refractory phase of between 5 and 20 s. In vitro investigations have demonstrated
      that this refractory period is due in large part to the persistent activation of
      the hyperpolarization-activated cation current Ih in thalamocortical cells. Here,
      we show that increases in [Ca2+]i due to rebound Ca2+ bursts result in persistent
      activation of Ih resulting from a positive shift in the activation curve of this
      current. The dynamical upregulation and persistent activation of Ih is the
      critical determinant of the time course of the refractory period. These findings
      demonstrate that periodicity in neural network oscillations may be generated
      through an interaction between the electrophysiological properties and
      intracellular signaling pathways of the constituent neurons.

PMID- 9539129
TI  - Slob, a novel protein that interacts with the Slowpoke calcium-dependent
      potassium channel.
AB  - Slob, a novel protein that binds to the carboxy-terminal domain of the Drosophila
      Slowpoke (dSlo) calcium-dependent potassium channel, was identified with a yeast
      two-hybrid screen. Slob and dSlo coimmunoprecipitate from Drosophila heads and
      heterologous host cells, suggesting that they interact in vivo. Slob also
      coimmunoprecipitates with the Drosophila EAG potassium channel but not with
      Drosophila Shaker, mouse Slowpoke, or rat Kv1.3. Confocal fluorescence microscopy
      demonstrates that Slob and dSlo redistribute in cotransfected cells and are
      colocalized in large intracellular structures. Direct application of Slob to the
      cytoplasmic face of detached membrane patches containing dSlo channels leads to
      an increase in channel activity. Slob may represent a new class of multi
      functional channel-binding proteins.

PMID- 9539130
TI  - Mode switching kinetics produced by a naturally occurring mutation in the
      cytoplasmic loop of the human acetylcholine receptor epsilon subunit.
AB  - We describe the genetic and kinetic defects in a congenital myasthenic syndrome
      caused by heteroallelic mutations of the acetylcholine receptor (AChR) epsilon
      subunit gene. The mutations are an in-frame duplication of six residues in the
      long cytoplasmic loop (epsilon1254ins18) and a cysteine-loop null mutation
      (epsilonC128S). The epsilon1254 ins18 mutation causes mode switching in the
      kinetics of receptor activation in which three modes activate slowly and
      inactivate rapidly. The epsilon1245ins18-AChR at the endplate shows abnormally
      brief activation episodes during steady state agonist application and appears
      electrically silent during the synaptic response to acetylcholine. The phenotypic
      consequences are endplate AChR deficiency, simplification of the postsynaptic
      region, and compensatory expression of fetal AChR that restores electrical
      activity at the endplate and rescues the phenotype.

PMID- 9539131
TI  - Aberrant RNA processing in a neurodegenerative disease: the cause for absent
      EAAT2, a glutamate transporter, in amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that is
      characterized by selective upper and lower motor neuron degeneration, the
      pathogenesis of which is unknown. About 60%-70% of sporadic ALS patients have a
      30%-95% loss of the astroglial glutamate transporter EAAT2 (excitatory amino acid
      transporter 2) protein in motor cortex and spinal cord. Loss of EAAT2 leads to
      increased extracellular glutamate and excitotoxic neuronal degeneration. Multiple
      abnormal EAAT2 mRNAs, including intron-retention and exon-skipping, have now been
      identified from the affected areas of ALS patients. The aberrant mRNAs were
      highly abundant and were found only in neuropathologically affected areas of ALS
      patients but not in other brain regions. They were found in 65% of sporadic ALS
      patients but were not found in nonneurologic disease or other disease controls.
      They were also detectable in the cerebrospinal fluid (CSF) of living ALS
      patients, early in the disease. In vitro expression studies suggest that proteins
      translated from these aberrant mRNAs may undergo rapid degradation and/ or
      produce a dominant negative effect on normal EAAT2 resulting in loss of protein
      and activity. These findings suggest that the loss of EAAT2 in ALS is due to
      aberrant mRNA and that these aberrant mRNAs could result from RNA processing
      errors. Aberrant RNA processing could be important in the pathophysiology of
      neurodegenerative disease and in excitotoxicity. The presence of these mRNA
      species in ALS CSF may have diagnostic utility.

PMID- 9539132
TI  - An Alzheimer's disease-linked PS1 variant rescues the developmental abnormalities
      of PS1-deficient embryos.
AB  - Mutations in presenilin 1 (PS1) cosegregate with approximately 25% of early onset
      familial Alzheimer's disease (FAD) pedigrees. A variety of in vitro and in vivo
      paradigms have established that one mechanism by which PS1 variants cause AD is
      by elevating the production of highly amyloidogenic Abeta1-42/43 peptides. PS1 is
      homologous to sel-12, a C. elegans protein that facilitates signaling mediated by
      the Notch/lin-12 family of receptors. Wild-type human PS1 complements an egg
      laying defect in C. elegans lacking sel-12, while FAD-linked PS1 variants exhibit
      reduced rescue activity. These data suggested that mutant PS1 may cause disease
      as a result of reduction in PS1 function. To test the function of FAD-linked PS1
      in mammals, we examined the ability of the A246E PS1 variant to complement the
      embryonic lethality and axial skeletal defects in mice lacking PS1. Finally, to
      examine the influence of reduced PS1 levels on Abeta production, we quantified
      Abeta1-42/43 peptide levels in PS1 heterozygous null mice (PS1[+/-] mice). We now
      report that both human wild-type and A246E PS1 efficiently rescue the phenotypes
      observed in PS1(-/-) embryos, findings consistent with the view that FAD-linked
      PS1 mutants retain sufficient normal function during mammalian embryonic
      development. Moreover, the levels of Abeta1-42/43 and Abeta1-40 peptides between
      PS1(+/-) and control mice are indistinguishable. Collectively, these data lead us
      to conclude that mutant PS1 causes AD not by loss of normal PS1 function but by
      influencing amyloid precursor protein (APP) processing in a manner that elevates
      Abeta1-42/43 production.

PMID- 9539133
TI  - Mutant human presenilin 1 protects presenilin 1 null mouse against embryonic
      lethality and elevates Abeta1-42/43 expression.
AB  - Mutations in presenilin 1 (PS1) are linked to early onset of familial Alzheimer's
      disease (FAD) and are shown to foster production of Abeta1-42/43 in FAD patients
      and transgenic mice. PS1 null mice are embryonic lethal and exhibit axial
      skeleton malformation and CNS defects. We show that transgenic mouse lines
      expressing either the wild-type human PS1 protein or human PS1 with the A246E FAD
      mutation can rescue the PS1 knockout mouse from embryonic lethality to similar
      degrees, indicating that the mutation does not lead to loss of PS1 function
      during development. Furthermore, a 50% reduction of PS1 activity in PS1(+/-) mice
      does not lead to Abeta1-42/43 increase, whereas expression of human mutant PS1 on
      murine PS1 null background is sufficient to elevate Abeta1-42/43, supporting a
      gain-of-function activity as the result of the PS1 mutation.

PMID- 9539134
TI  - Analysis of three human interleukin 5 structures suggests a possible receptor
      binding mechanism.
AB  - We compared three crystal structures of human interleukin 5 (hIL5) expressed in
      either E. coli (hIL5E.coli), Sf9 cells (hIL5sf9) or Drosophila cells
      (hIL5Drosophila). The dimeric hIL5 structures show subtle but significant
      conformational differences which are probably a consequence of the different
      crystallization conditions trapping this protein into one of two states. We refer
      to these two distinct conformations as the 'open' and 'tight' state, according to
      the packing around the cleft between the two subunits. We hypothesize that these
      two stable conformational states reflect the structure of the free or receptor
      bound hIL5.

PMID- 9539135
TI  - The yeast gene YJR025c encodes a 3-hydroxyanthranilic acid dioxygenase and is
      involved in nicotinic acid biosynthesis.
AB  - We have deleted the yeast gene YJR025c and shown that this leads to an auxotrophy
      for nicotinic acid. The deduced protein sequence of the gene product is
      homologous to the human 3-hydroxyanthranilic acid dioxygenase (EC 1.13.11.6)
      which is part of the kynurenine pathway for the degradation of tryptophan and the
      biosynthesis of nicotinic acid. In cell-free extracts the 3-hydroxyanthranilic
      acid dioxygenase activity is proportional to the copy number of the YJR025c gene.
      As YJR025c encodes the yeast 3-hydroxyanthranilic acid dioxygenase, we have named
      this gene BNA1 for biosynthesis of nicotinic acid.

PMID- 9539136
TI  - Carboxy-terminal truncation of long-tailed amyloid beta-peptide is inhibited by
      serine protease inhibitor and peptide aldehyde.
AB  - The 42/43-residue amyloid beta-peptide (Abeta) is widely believed to play a major
      role in Alzheimer's disease. The present study shows that the rat brain contains
      a carboxypeptidase that efficiently deletes three amino acids from Abeta1-43. The
      carboxypeptidase activity in the brain was completely inhibited by 1 mM
      phenylmethylsulfonyl fluoride, suggesting the protease is a serine
      carboxypeptidase. The carboxy-terminal truncation of Abeta1-43 was moderately
      inhibited by carbobenzoxy-Leu-leucinal, carbobenzoxy-Leu-Leu-leucinal, and
      carbobenzoxy-Leu-Leu-norvalinal, and weakly by antipain. The present data suggest
      that the serine carboxypeptidase contributes to the generation of short-tailed
      Abeta peptides and is important in the intracellular clearance of Abeta1-42/43 in
      brains.

PMID- 9539137
TI  - Differences in F9 and 5.51 cell elasticity determined by cell poking and atomic
      force microscopy.
AB  - We studied the elasticity of both a wild type (F9) mouse embryonic carcinoma and
      a vinculin-deficient (5.51) cell line, which was produced by chemical
      mutagenesis. Using cell poking, we measured the effects of loss of vinculin on
      the elastic properties of these cells. F9 cells were about 20% more resistant to
      indentation by the cell poker (a glass stylus) than were 5.51 cells. Using the
      atomic force microscope to map the elasticity of wild type and vinculin-deficient
      cells by 128 X 128 force scans, we observed a correlation of elasticity with cell
      poking elastometric measurements. These findings, as well as previous atomic
      force, rheologic, and magnetometric measurements [Goldmann and Ezzell, Exp. Cell
      Res. 226 (1996) 234-237; Ezzell et al., Exp. Cell Res. 231 (1997) 14-26],
      indicate that vinculin is an integral part of the cytoskeletal network.

PMID- 9539139
TI  - Effect of bicarbonate on the S2 multiline EPR signal of the oxygen-evolving
      complex in photosystem II membrane fragments.
AB  - Removal of bicarbonate from spinach photosystem II BBY particles by means of
      washing in a CO2-free medium results in the loss of their capability to
      accumulate the S2 multiline EPR signal upon continuous illumination at 190 K.
      Addition of 1 mM NaHCO3 before illumination leads to a 50-60% restoration of the
      multiline signal. Similarly, in BBY particles depleted of Mn by treatment with 1
      M Tris-HCl (pH 8.0) and 0.5 M MgCl2, re-addition of MnCl2 in the presence of 1 mM
      NaHCO3 results in a partial restoration (approximately 30%) of the S2 multiline
      EPR signal of the Mn cluster, while in the absence of NaHCO3 no restoration is
      observed. The results provide further evidence that bicarbonate is essential for
      maintaining the Mn-containing oxygen-evolving complex of PS II in a functionally
      active form.

PMID- 9539140
TI  - N-linked glycosylation of Drosophila rhodopsin occurs exclusively in the amino
      terminal domain and functions in rhodopsin maturation.
AB  - Immature Drosophila rhodopsin is N-glycosylated, but undergoes complete
      deglycosylation during the process of protein maturation. In order to elucidate
      the site of glycosylation and its role in rhodopsin synthesis, we investigated
      the in vitro and in vivo synthesis of rhodopsin whose putative N-glycosylation
      sites (Asn-20 and Asn-196) were replaced by isoleucine. The results demonstrated
      that immature rhodopsin binds a single oligosaccharide chain exclusively at Asn
      20 in the N-terminal extracellular domain. Furthermore, the results gave the
      first evidence directly indicating that deletion of the oligosaccharide chain
      markedly impedes rhodopsin maturation.

PMID- 9539138
TI  - Molecular cloning and functional characterization of the cDNA encoding the murine
      thiopurine S-methyltransferase (TPMT).
AB  - Thiopurine S-methyltransferase (TPMT) is a cytosolic enzyme that catalyzes S
      methylation of aromatic and heterocyclic sulfhydryl compounds, including
      anticancer and immunosuppressive thiopurines. Here we report the isolation and
      functional characterization of the murine TPMT cDNA. The screening of expressed
      sequence tags database led to isolation of a murine cDNA clone containing an
      uninterrupted ORF encoding the protein with an amino acid sequence that is 82%
      similar and 78% identical to the human TPMT. The expression product of the murine
      cDNA in rabbit reticulocyte and wheat germ lysate coupled transcription
      translation systems showed TPMT enzymatic activity. We conclude that the isolated
      cDNA clone represents the murine TPMT cDNA.

PMID- 9539141
TI  - Peroxidative damage to cardiac mitochondria: cytochrome oxidase and cardiolipin
      alterations.
AB  - Rat heart mitochondrial membranes exposed to the free radicals generating system
      tert-butylhydroperoxide/Cu2+ undergo lipid peroxidation as evidenced by the
      accumulation of thyobarbituric acid reactive substances. Mitochondrial lipid
      peroxidation resulted in a marked loss of both cytochrome c oxidase activity and
      cardiolipin content. The alterations in the properties of cytochrome c oxidase
      were confined to a decrease in the maximal activity (Vmax) with no change in the
      affinity (Km) with respect to the substrate cytochrome c. Various lipid soluble
      antioxidants could prevent the lipid peroxidation reaction and the associated
      loss of cytochrome c oxidase activity. External added cardiolipin but no other
      phospholipids, nor peroxidized cardiolipin was able to prevent the loss of
      cytochrome oxidase activity induced by lipid peroxidation. These results
      establish a close correlation between oxidative damage to cardiolipin and
      alterations in the cytochrome oxidase activity and may prove useful in probing
      molecular mechanism of free radicals induced peroxidative damage of mitochondria
      which has been proposed to contribute to aging and to chronic degenerative
      diseases.

PMID- 9539142
TI  - A novel subtype of G-protein-coupled receptor kinase, GRK7, in teleost cone
      photoreceptors.
AB  - Two kinds of retinal cDNA fragments (OIGRK-R and -C) encoding the putative G
      protein-coupled receptor kinases (GRKs) were isolated from medaka, Oryzias
      latipes. OIGRK-R appears to be closely related to the rhodopsin kinase (RK) found
      in the outer segments of mammalian photoreceptors, but the deduced amino acid
      sequence of OIGRK-C shows less than 50% identity to those of GRKs known to date,
      suggesting that OIGRK-C is a novel GRK subtype (GRK7). The mRNA of OIGRK-R is
      detectable in rods, and that of OIGRK-C is found in all four types of cone
      photoreceptor. The C-terminal of OIGRK-R has a consensus sequence for
      farnesylation, whereas, surprisingly, OIGRK-C has a consensus sequence for
      geranylgeranylation. Our result are consistent with the concept that lower
      vertebrates have rod- and cone-specific opsin kinases.

PMID- 9539143
TI  - Regulation of a plant plasma membrane sucrose transporter by phosphorylation.
AB  - The protein phosphatase inhibitor okadaic acid (OA) either provided directly to
      sugar beet (Beta vulgaris L.) leaf discs or infiltrated in the leaf blade rapidly
      inhibited sucrose uptake. Methyl okadaic acid, a biologically inactive analogue
      of OA, had only a marginal effect on uptake. OA inhibited proton-motive force
      driven uptake of sucrose into plasma membrane vesicles, without affecting their
      proton permeability. OA did not significantly affect the amount of sucrose
      transporters present in the vesicles, as estimated by ELISA with specific
      antibodies. It is concluded that OA directly inhibits the activity of a H+
      sucrose cotransporter of the plant plasma membrane, likely by maintaining it in a
      phosphorylated form.

PMID- 9539144
TI  - A 1H NMR comparative study of human adult and fetal hemoglobins.
AB  - The affinities of the individual subunits in human adult and fetal hemoglobins to
      azide ion have been determined from the combined analysis of NMR and optical
      titration data. Structural and functional non-equivalence of the constituent
      subunits, i.e. alpha and beta subunits in human adult hemoglobin and alpha and
      gamma subunits in human fetal hemoglobin, has been confirmed. The function of the
      alpha subunits, which are common to both hemoglobins, is essentially identical in
      these hemoglobins and, in spite of the substitutions of 39 amino acid residues
      between beta and gamma subunits, they exhibit similar azide ion affinities. The
      present study also demonstrates that the NMR spectral comparison between the two
      proteins provides signal assignments to the individual subunits in intact
      tetramer.

PMID- 9539145
TI  - Dehydroepiandrosterone sulfate (DHEAS): identification of a carrier protein in
      human liver and brain.
AB  - Dehydroepiandrosterone sulfate (DHEAS) is the major circulating steroid in man.
      Pharmacologically, it exerts marked neuropsychiatric effects. Since no target
      receptor has been identified, we investigated whether the organic anion
      transporting polypeptide (OATP), a multispecific steroid carrier, transports
      DHEAS. Expression of the human liver OATP in Xenopus laevis oocytes resulted in
      high-affinity, partially Na+-dependent uptake of [3H]DHEAS (Km: 6.6 micromol/l).
      DHEAS transport was inhibited by bromosulfophthalein, bile acids, sulfated
      estrogens and dexamethasone. Northern blot analysis showed widespread expression
      of OATP in human brain. These data identify OATP as the first known target
      protein of DHEAS in human liver and brain.

PMID- 9539146
TI  - Determination of the human c-Abl consensus DNA binding site.
AB  - c-Abl tyrosine kinase, an essential protein of the cell cycle signalling
      pathways, is implicated in the regulation of RNA polymerase II activity,
      apoptosis and DNA repair. Its DNA binding activity is important for its
      biological functions. However, the molecular basis of c-Abl interaction with DNA
      remains largely unclear. We delimited the human c-Abl DNA binding domain and
      identified its preferred binding site, 5'-A(A/C)AACAA(A/C). The central AAC motif
      is highly conserved and constitutes the major core element in the binding sites.
      EMSAs and footprinting experiments were performed to explore how the c-Abl fusion
      protein recognizes specific sequences in DNA.

PMID- 9539147
TI  - Anti-peptide antibodies specific to rat endothelin-converting enzyme-1 isoforms
      reveal isoform localisation and expression.
AB  - Endothelin-converting enzyme-1 (ECE-1) is a critical enzyme in the biosynthesis
      of the potent vasoconstrictor peptide endothelin and exists in several isoforms.
      Anti-peptide antibodies raised against epitopes in the distinct N-terminal
      cytoplasmic tails of the rat ECE-1 isoforms have been obtained. By using these
      antibodies in Western blot analysis and immunofluorescence studies, we have shown
      that cultures of transformed rat lung vascular endothelial cells treated with the
      metalloprotease inhibitor phosphoramidon and untreated cells express ECE-1alpha
      only, whereas human umbilical vein endothelial cells express ECE-1alpha and ECE
      1beta. The ECE-1 isoforms expressed in CHO-K1 cells transfected with rat cDNA to
      ECE-1alpha and ECE-1beta could be immunoprecipitated by using the appropriate
      isospecific antibody.

PMID- 9539148
TI  - Papain proteolysis releases a soluble NADPH dependent diaphorase activity from
      bovine neutrophil membranes.
AB  - An NADPH dependent cytochrome c reductase has been purified from resting bovine
      neutrophil membranes. A high degree of purification, approaching homogeneity, is
      indicated by the presence of a single 75 kDa protein band on silver stained SDS
      PAGE (10%). The purified protein catalyzes as well an NADPH dependent reduction
      of iodonitrotetrazolium violet (INT). Limited papain digestion of the purified
      preparation produces a 65 kDa product which retains both enzymatic activities. In
      a similar fashion papain digestion of the plasma membrane bound protein generates
      a fully active soluble NADPH dependent INT and cytochrome c reductase preparation
      (65 kDa). Proteolytic cleavage would appear to occur at a protein-membrane anchor
      remote from the proteins catalytic site. The cytochrome c reductase acts
      independently of the O2-generating cytochrome b558, a leukocyte plasma membrane
      protein which also catalyzes an NADPH dependent INT reduction.

PMID- 9539149
TI  - A new family of orphan G protein-coupled receptors predominantly expressed in the
      brain.
AB  - The cloning of a cDNA encoding a G protein-coupled receptor homologous to the
      endothelin type B receptor, but unable to bind endothelin, was recently reported
      and termed ET(B)R-LP. We report here the isolation of a human cDNA encoding a
      receptor that is highly related to ET(B)R-LP and which was therefore termed
      ET(B)R-LP-2. Comparison of the two amino acid sequences revealed 68% overall
      homology and 48% identity. As is the case for ET(B)R-LP, the new receptor is
      strongly expressed in the human central nervous system (e.g. in cerebellar
      Bergmann glia, cerebral cortex, internal capsule fibers). Membranes of HEK-293
      cells stably expressing ET(B)R-LP-2 did not bind endothelin-1, endothelin-2,
      endothelin-3, bombesin, cholecystokinin-8 or gastrin-releasing peptide.

PMID- 9539150
TI  - Nitric oxide protects blood-brain barrier in vitro from hypoxia/reoxygenation
      mediated injury.
AB  - A cell culture model of blood-brain barrier (BBB, coculture of rat brain
      endothelial cells with rat astrocytes) was used to investigate the effect of
      nitric oxide (.NO) on the damage of the BBB induced by hypoxia/reoxygenation
      (H/R). Permeability coefficient of fluorescein across the endothelium was used as
      a marker of BBB tightness. The permeability coefficient increased 5.2 times after
      H/R indicating strong disruption of the BBB. The presence of the .NO donor S
      nitroso-N-acetylpenicillamine (SNAP, 30 microM), authentic .NO (6 microM) or
      superoxide dismutase (50 units/ml) during H/R attenuated H/R-induced increase in
      permeability. 30 microM SNAP or 6 microM .NO did not influence the function of
      BBB during normoxia, however, severe disruption was observed using 150 microM of
      SNAP and more than 24 microM of .NO. After H/R of endothelial cells, the content
      of malondialdehyde (MDA) increased 2.3 times indicating radical-induced
      peroxidation of membrane lipids. 30 microM SNAP or 6 microM authentic .NO
      completely prevented MDA formation. The results show that .NO may effectively
      scavenge reactive oxygen species formed during H/R of brain capillary endothelial
      cells, affording protection of BBB at the molecular and functional level.

PMID- 9539151
TI  - G-protein betagamma-binding domains regulate insulin exocytosis in clonal
      pancreatic beta-cells.
AB  - We have tested the putative role of G-protein beta-subunits in insulin exocytosis
      by transient expression of betagamma-binding proteins targeted to the plasma
      membrane. The PH domain of the G-protein-linked receptor kinase 2 fused to the
      transmembrane domain of a cell surface receptor and the alpha-subunit of the
      retinal G-protein transducin inhibited stimulated insulin release from intact and
      permeabilised HIT-T15 cells. This effect cannot be imputed to an increase in free
      Galpha, as the RGS protein RGS3 did not reverse this effect. Among the isoforms
      of Gbeta examined, Gbeta2 was detected on the plasma membrane by confocal
      immunomicroscopy. These observations suggest a role for G-protein betagamma
      subunits in insulin exocytosis.

PMID- 9539152
TI  - Contribution of the second transmembrane helix of the secretin receptor to the
      positioning of secretin.
AB  - The secretin amino-terminal residues are essential for high affinity binding to
      its cognate receptor and for its biological activity. Mutation of the [Asp3]
      residue of secretin to [Asn3] decreased the ligand's affinity for the rat wild
      type receptor 100-300-fold. Receptor mutations in the transmembrane 2 domain and
      the beginning of the first extracellular loop allowed the identification of three
      residues involved in recognition of the [Asp3] residue: D174, K173 and R166.
      Mutation of K173 and D174 not only reduced the secretin and [Asn3]secretin
      affinities, but also changed the receptor's selectivity as judged by a decreased
      secretin and [Asn3]secretin potency ratio. The most striking effect was observed
      when R166 was mutated to Q, D or L. This led to receptors with a very low
      affinity for secretin but an up to 10-fold higher affinity than the wild-type
      receptor for [Asn3]secretin. This suggested that R166, highly conserved in that
      subgroup of receptor, is a major determinant for the recognition of the [Asp3] of
      the ligand.

PMID- 9539153
TI  - Autocrine regulation of endothelial exocytosis: von Willebrand factor release is
      induced by prostacyclin in cultured endothelial cells.
AB  - Vascular endothelial cells respond to external stimuli by altering the secretion
      of several bioactive molecules, including von Willebrand factor (vWf),
      prostacyclin (PGI2) and nitric oxide (NO). The release of all three molecules is
      regulated by a rise in cytosolic calcium ([Ca2+]i). In the present study we
      investigated whether cAMP-dependent signaling provides differential regulation of
      these effector systems by modulating the effect of [Ca2+]i in cultured human
      endothelial cells. The stable PGI2 analog iloprost, like other cAMP-raising
      agents (forskolin and adenosine), caused an acute dose-dependent increase in vWf
      release and potentiated the secretory response to thrombin. In contrast,
      iloprost, forskolin and adenosine failed to induce PGI2 release and inhibit
      thrombin-induced release. Our findings indicate cAMP-raising agents have opposite
      effects on [Ca2+]i-mediated vWf secretion and PGI2 release. PGI2 may potentiate
      vWf release and inhibit its own release in an autocrine manner.

PMID- 9539154
TI  - The olfactory adenylyl cyclase type 3 is expressed in male germ cells.
AB  - Elements of the olfactory pathway, such as receptors, receptor-desensitization
      machinery, and cyclic nucleotide-gated channels, are expressed in male germ
      cells. Here we report the expression, in rat testis, of both adenylyl cyclase
      type 3 (AC3) and the olfactory G protein subunit, G(alpha)olf. Both are expressed
      in the same sub-population of germ cells, pachytene spermatocytes to spermatids,
      and in residual bodies. Neither AC3 nor G(alpha)olf was found in Sertoli or in
      peritubular cells, as shown by Western blotting and immunocytochemical analyses.
      It thus appears that male germ cells contain all the elements of the signaling
      cascade present in olfactory cells.

PMID- 9539155
TI  - Pro- and anti-apoptotic effects of K+ in HeLa cells.
AB  - The present study determined the effects of osmotic stress induced by sorbitol
      and KCl on apoptosis. Sorbitol induced apoptosis, activated the mitogen-activated
      protein kinase (MAPK) family and stimulated accumulation of cytosolic cytochrome
      c and procaspase-3 cleavage. KCl (0.2 M) also activated the MAPKs and induced
      cytosolic cytochrome c accumulation but did not induce procaspase-3 cleavage or
      apoptosis and was protective against sorbitol-induced apoptosis. However, when
      cells were exposed to KCl for 1 h, washed and returned to isotonic medium,
      caspase-3 was rapidly cleaved and apoptosis induced. We conclude that
      hyperosmotic KCl initiates early events in apoptosis but blocks caspase-3
      activation by preventing the loss of intracellular K+.

PMID- 9539156
TI  - A phosphatase activity in Xenopus oocyte extracts preferentially dephosphorylates
      the MPM-2 epitope.
AB  - MPM-2 antigens are a large family of mitotic phosphoproteins that contain similar
      phosphoepitopes recognized by the anti-phosphoepitope antibody MPM-2 (MPM-2
      epitopes). These proteins are phosphorylated during M phase induction and
      dephosphorylated from the onset of anaphase through interphase. Since biochemical
      characterization of the MPM-2 epitope phosphatase requires a specific assay for
      its activity, we tested different methods for measurement of the MPM-2 epitope
      phosphatase activity in crude cell lysates. First, an ELISA-based assay was
      designed that measured the phosphatase-induced reduction of the MPM-2 reactivity
      in crude M phase cell lysates. Using this assay to follow the phosphatase
      activity during sequential chromatography of Xenopus oocyte extracts, one
      predominant peak of phosphatase activity was detected which was separated from
      the majority of PP1 and PP2A activities. This phosphatase activity
      dephosphorylated the MPM-2 epitope on multiple MPM-2 antigens. The second method
      measured dephosphorylation of cdc25, a known MPM-2 antigen. Two major peaks of
      cdc25 dephosphorylating activities were detected during the sequential
      chromatography, one that copurified with the major peak of MPM-2 epitope
      phosphatase activity, and the other with the major peak of PP2A activity.
      Finally, we examined whether GST-MPM2, a fusion protein between glutathione S
      transferase and a 19-residue peptide that contained two representative MPM-2
      epitope sequences, could be dephosphorylated efficiently and specifically by the
      major MPM-2 epitope phosphatase activity in Xenopus oocyte extracts. Neither the
      crude extract nor the partially purified MPM-2 epitope phosphatase activity
      efficiently dephosphorylated the MPM-2 epitope on GST-MPM2. These results
      demonstrate that the ELISA-based assay preferentially detects the MPM-2 epitope
      phosphatase activity in crude cell lysates which may represent a physiological
      MPM-2 epitope phosphatase.

PMID- 9539157
TI  - Molecular cloning of a cDNA encoding a pollen extracellular protein as a
      potential source of a pollen allergen in Brassica rapa.
AB  - A polyclonal antiserum was raised against the extracellular pollen proteins of
      Brassica rapa and used for screening the expression cDNA libraries made from
      immature anthers. We obtained five groups of cDNA clones, including cDNAs similar
      to PCP1, thioredoxin, and lipid transfer protein (LTP). Recombinant protein of
      the cDNA clone showing sequence similarity to LTP was demonstrated to bind IgE of
      a patient allergic to Brassica pollen. The cDNA clone reported here, therefore,
      represents a novel pollen allergen of Brassica rapa.

PMID- 9539158
TI  - NO catastrophes in vivo as a result of micellar catalysis.
AB  - Micellar catalysis plays a crucial role in NO metabolism because media in vivo
      are heterogeneous and the concentration of NO in different phases at different
      levels of solubility differs by degrees of magnitude. The relative volumes of the
      hydrophobic phases are usually small. At small volumes (which are calculated) of
      these phases the reaction rates of NO metabolism change. The dependence on the
      relative volumes is resonance-like. Not only regulation, but bifurcations and
      catastrophes are possible in vivo as a result of this changing due to the small
      change of effectiveness of micellar catalysis.

PMID- 9539160
TI  - Chemotactic and osmotic signals share a cGMP transduction pathway in
      Dictyostelium discoideum.
AB  - In the ameboid eukaryote Dictyostelium discoideum, chemotactic stimulation by
      cAMP induces an increase of intracellular cGMP and subsequently the
      phosphorylation of myosin heavy chain II. Resistance to high osmotic stress also
      requires transient increases of intracellular cGMP and phosphorylation of myosin
      heavy chain II, although the kinetics is much slower than for chemotaxis. To
      examine if chemotaxis and osmotic stress share common signaling components we
      systematically analyzed the osmotic cGMP response and survival in chemotactic
      mutants with altered cGMP signaling. Null mutants with deletions of cell surface
      cAMP receptors or the associated GTP-binding proteins Galpha2 and Gbeta show no
      cAMP-induced cGMP response and chemotaxis; in contrast, osmotic stress induces
      the normal cGMP accumulation and survival. The same result was obtained with the
      non-chemotactic mutant KI-10, which lacks the activation of guanylyl cyclase by
      cAMP. This indicates that these components are required for chemotaxis but not
      osmotic cGMP signaling and survival. The potential guanylyl cyclase null mutant
      KI-8 shows no chemotaxis, no osmotic cGMP increase and reduced survival in high
      osmolarity. Two types of cGMP-binding protein mutants, KI-4 and KI-7, also show
      reduced tolerance during high osmotic stress. Taken together, these observations
      clarify that chemotactic and osmotic signals are detected by different
      mechanisms, but share a cGMP signaling pathway.

PMID- 9539159
TI  - Involvement of the YIGSR sequence of laminin in protein tyrosine phosphorylation.
AB  - We have examined the mechanism of signaling by the 67 kDa YIGSR binding protein
      of laminin and its properties in neuroblastoma cells. Ligand displacement
      analysis showed that the interaction with the C(YIGSR)3-NH2 peptide amide is of
      intermediate affinity (1.5 x 10[-7] M). Cross-linking experiments with sulfo-MBS
      detected an additional protein with a molecular mass of 116 kDa that binds the
      YIGSR sequence. Incubation of neuroblastoma cells with C(YIGSR)3-NH2 peptide
      amide or antibody directed against the 67 kDa laminin binding protein induces
      tyrosine phosphorylation of proteins with a molecular mass ranging from 115 to
      130 kDa and another heterogeneous protein group of 32 kDa.

PMID- 9539161
TI  - Iron attenuates nitric oxide level and iNOS expression in endotoxin-treated mice.
AB  - The effect of exogenous Fe-citrate complex (Fe doses of 120 and 240 micromol/kg)
      on nitric oxide (NO) production in vivo has been studied in blood and liver
      tissue of endotoxin-treated mice. Fe-citrate complex was administered to mice
      subcutaneously at the same time with intravenous injection of Escherichia coli
      lipopolysaccharide (LPS). Iron-dependent decrease in NO2-/NO3- and nitrosyl
      hemoglobin levels in blood of animals was detected at 6 h after LPS
      administration, suggesting systemic attenuation of NO generation. NO production
      in the liver tissue of LPS-treated mice was decreased after Fe administration
      judging from the amount of mononitrosyl-iron complexes formed in the tissue by
      diethyldithiocarbamate. The iNOS protein determination in the liver tissue of LPS
      treated mice demonstrated iron-dependent inhibition of iNOS expression. We have
      found previously that exogenous iron does not affect systemic NO level when it is
      given at 6 h after LPS injection, i.e. after iNOS expression. This is a first
      report demonstrating iron-dependent iNOS down-regulation in endotoxin-treated
      mice.

PMID- 9539162
TI  - Plasmodium falciparum glutathione metabolism and growth are independent of
      glutathione system of host erythrocyte.
AB  - Plasmodium falciparum parasites grew normally in glutathione (GSH)-depleted
      normal and G6PD-deficient (Mediterranean variant) erythrocytes (RBC). Growth
      inhibition was observed only at less than approximately 6-12% residual GSH.
      Parasites studied separately with the Sendai virus technique synthesized GSH de
      novo and regenerated reduced GSH 10-20 times faster than non-parasitized RBC.
      Electron spin resonance measurement of Tempol reduction indicated that the
      ability to reduce free radicals was restricted to the parasite. The marked efflux
      of oxidized GSH was mainly derived from the parasite. In conclusion, parasites
      are endowed with powerful and host-independent mechanisms which de novo
      synthesize or regenerate GSH and allow undisturbed parasite development in GSH
      depleted RBC.

PMID- 9539163
TI  - Inhibition of matrix metalloproteinase 2 maturation and HT1080 invasiveness by a
      synthetic furin inhibitor.
AB  - The close correlation observed between matrix metalloproteinase 2 (MMP-2)
      activation and metastatic progression in various tumors suggests that MMP-2 is a
      'master switch' triggering tumor spread. Recently, membrane type 1 MMP (MT1-MMP)
      was identified as a potential physiological activator of MMP-2. Like all other
      MMPs, MT1-MMP possesses a pro-domain which must be removed for the enzyme to
      acquire its catalytic potential. The presence of a typical recognition motif
      (RXKR) for the furin-like convertases at the end of its pro-domain suggests a
      potential role for these proteinases in MT1-MMP processing. In order to evaluate
      the implication of furin in pro-MT1-MMP processing, we treated HT1080 cells with
      a synthetic furin inhibitor and monitored their ability to activate pro-MMP-2 as
      well as their invasive potential. Our results demonstrated that the furin
      inhibitor decreased pro-MT1-MMP processing as well as pro-MMP-2 activation and
      cell invasiveness. Therefore, our data bring further evidence that furin is a key
      factor in the maturation of MMPs associated with the invasive and metastatic
      potential of tumor cells.

PMID- 9539164
TI  - Beta-carotene to zeaxanthin conversion in the rapid turnover of the D1 protein of
      photosystem II.
AB  - The carotenoid composition was investigated during enhanced D1 protein turnover
      in Chlamydomonas reinhardtii exposed to high light. After 2 h of high light there
      was no loss of the D1 protein yet. However, the beta-carotene content was
      significantly reduced. In parallel, an increase of the zeaxanthin content was
      found, which was higher than can be accounted for by the light-induced de
      epoxidation of violaxanthin in the xanthophyll cycle reactions. We therefore
      assume that beta-carotene of photosystem II (PS II) is hydroxylated to zeaxanthin
      under high light stress. Inhibitors of carotene biosynthesis led to the loss of
      both PS II activity and D1 protein, indicating the requirement of beta-carotene
      synthesis for the reassembly of PS II in high light. Diuron blocked D1 protein as
      well as beta-carotene turnover. In the presence of chloramphenicol -- which
      allows just one turnover of the D1 protein -- 15% of the total beta-carotene was
      lost, calculated to be two beta-carotene.

PMID- 9539165
TI  - The oxidation of naphthalene and pyrene by cytochrome P450cam.
AB  - Mutants of the heme monooxygenase cytochrome P450cam in which Y96 had been
      replaced with hydrophobic residues, have been shown to oxidise naphthalene and
      pyrene with rates one to two orders of magnitude faster than the wild-type.
      Naphthalene was oxidised to 1- and 2-naphthol, probably via the 1,2-oxide
      intermediate. In the case of the Y96F mutant, naphthalene was oxidised at a rate
      comparable to camphor. Pyrene oxidation gave 1,6- and 1,8-pyrenequinone with no
      evidence for attack at the K-region, in contrast to mammalian enzymes. The
      results show that the Y96 residue plays a key role in controlling the substrate
      range of P450cam.

PMID- 9539166
TI  - Immobilized apo-myoglobin, a new stable reagent for measuring rates of heme
      dissociation from hemoglobin.
AB  - Apo-myoglobin covalently linked on CNBr-activated Sepharose 4B is proposed as a
      new heme acceptor for investigating the heme transfer reaction from hemoproteins.
      Immobilized apo-myoglobin has the desirable properties of an ideal heme acceptor
      in that it is characterized by a high affinity for ferric heme, a high stability
      towards denaturation even at physiological temperatures and can be lyophilized
      for long-term storage. The study of heme release from myoglobin at pH 5.0 and 37
      degrees C indicates that heme affinity is increased at least 10-fold relative to
      the soluble protein. Experiments with human hemoglobin allowed the estimation of
      the heme release rates from both alpha and beta chains and brought out the
      greater temperature sensitivity of the alpha chain heme-globin linkage.

PMID- 9539167
TI  - Existence of four acetylcholinesterase genes in the nematodes Caenorhabditis
      elegans and Caenorhabditis briggsae.
AB  - Three genes, ace-1, ace-2 and ace-3, respectively located on chromosomes X, I and
      II, were reported to encode acetylcholinesterases (AChEs) of classes A, B and C
      in the nematode Caenorhabditis elegans. We have previously cloned and sequenced
      ace-1 in the two related species C. elegans and C. briggsae. We report here
      partial sequences of ace-2 (encoding class B) and of two other ace sequences
      located in close proximity on chromosome II in C. elegans and C. briggsae. These
      two sequences are provisionally named ace-x and ace-y, because it is not possible
      at the moment to establish which of these two genes corresponds to ace-3. Ace-x
      and ace-y are transcribed in vivo as shown by RT-PCR and they are likely to be
      included in a single operon.

PMID- 9539168
TI  - The Farmington Consensus.

PMID- 9539169
TI  - The Farmington Consensus.

PMID- 9539170
TI  - Alcohol and criminal behaviour.
AB  - Substance abuse is a factor in some but not all incidents of crime: more than
      half of murders are committed when the killer is intoxicated. Males are more
      likely than females to be violent when consuming alcohol, and a past history of
      violence is predictive of future crime. The risk of violent behaviour is greater
      in subjects with dual diagnosis (e.g. alcohol dependence and psychiatric
      disorders). Offenders with an intellectual disability are overrepresented in
      prison and court populations, and more than 50% of them have a problem with
      alcohol. Since these subjects, in addition to intellectual disability and alcohol
      use, have psychiatric and behavioural problems, early recognition, in an effort
      to prevent future crimes, is an appropriate goal. Specific programmes have to
      address their particular needs.

PMID- 9539171
TI  - Aggressiveness, onset of dependence, and treatment outcome in socially well
      adapted alcoholics.
AB  - Current typologies of alcoholism derive from the whole spectrum of afflicted
      persons. One type is characterized by variables such as early onset of
      dependence, violence, and aggressiveness. In previous research, this has been
      shown to be correlated with poorer prognosis. We tested this association in a
      fairly homogeneous subgroup of 258 socially rather well-adjusted male inpatients.
      Aggressiveness was assessed psychometrically. As a group, patients did not differ
      from general population norms. However, age was negatively correlated with
      aggressiveness. Even after taking patients' age and duration of dependence into
      account, aggressiveness was associated with an early onset of dependence and
      further aspects of drinking history, thus confirming results from previous
      typology research. Overall treatment outcome after 6 and 12 months was quite
      good, but was not influenced by aggression.

PMID- 9539172
TI  - Treatment of alcoholic violent offenders: ethics and efficacy.
AB  - The published literature tends to find that the outcome of mandatory treatment
      for alcohol dependence is no worse than that for 'voluntary' treatment.
      Supervised disulfiram has been shown to improve outcome in Court-referred
      patients. When offenders take treatment offered as part of probation or a
      deferred sentence, they choose to do so, rather than face a penalty. It is not a
      'free' choice in the usual sense, but the outcome can be beneficial to the
      offender as well as to society and this helps to justify its use. Coping and
      social skills therapy have value, as probably have antipsychotic and
      antidepressant drugs in some cases. Supervised disulfiram has a role supported by
      controlled studies.

PMID- 9539173
TI  - Medico-legal aspects of alcohol, drugs, and criminality in Germany.

PMID- 9539174
TI  - What happens if a criminal can choose between detention and treatment: results of
      a 4-year experiment in The Netherlands.
AB  - In the Amsterdam region of The Netherlands, with 7000 drug addicts, 42% are
      estimated to commit criminal offences regularly. About 1500 drug users can be
      characterized as highly criminal drug addicts. The traditional reactions of the
      judicial system hardly contributed to a decrease in the number of these addicted
      delinquents. The Street Junk Project was therefore initiated in the late 1980s.
      In this contribution, the last 4 years of this project are evaluated. The Street
      Junk Project uses a forced-choice procedure in which arrested drug users can
      choose either a treatment or a detention option. The project has been moderately
      successful. A number of organizational and logistic problems meant that the
      project made a smaller impact than has been aimed for originally.

PMID- 9539175
TI  - The importance of family context in alcoholism.
AB  - In the present study, 56 chronic alcoholics were compared with 56 controls with
      no excessive drinking habits, all of them male. The drinking habits of their
      parents were studied, as were parental rearing, dyadic relations with the
      spouses, attachment to significant people, and the education they gave to their
      own children. It was noted that the alcoholics' parents had heavier drinking
      habits and could have acted as learning models. As regards the other
      characteristics, the dyadic cohesion, the global score of the education received
      from the father and the personal style of criticism/rejection in the education of
      their own children were underlined.

PMID- 9539176
TI  - Violence and alcoholism in the family: how are the children affected?
AB  - We made an evaluation of how children and adolescents are affected if they live
      in a family environment where violence associated with alcoholism is a feature.
      Interviews with 20 families and the use of psychological tests on their children
      were performed in this study. The study has demonstrated the existence of
      psychopathological disturbances in those families' children, whose immaturity and
      insecurity were expressed by aggressive behaviour or by depressive
      manifestations. It also became evident that there was a transgenerational
      alcoholism-violence frequency.

PMID- 9539177
TI  - Executive cognitive functions as mediators of alcohol-related aggression.
AB  - A large body of literature has documented a relation between executive cognitive
      functioning (ECF) and aggression. ECF encompasses 'higher-order' mental abilities
      such as attention, planning, organization, abstract reasoning, and self
      monitoring. ECF has been defined as the ability to utilize these functions to
      self-regulate goal-directed behaviour. The prefrontal cortex represents the
      primary neurological substrate that subserves ECF. Acute alcohol consumption has
      been shown to disrupt ECF/prefrontal cortical functioning. Literature is reviewed
      linking ECF/prefrontal cortical functioning, alcohol consumption, and aggressive
      behaviour. A hypothetical model, based on empirical data, is presented,
      suggesting that ECF/prefrontal cortical functioning is an underlying aetiological
      mechanism for the relation between acute alcohol consumption and aggressive
      behaviour.

PMID- 9539178
TI  - Serotonin and aggression and the alcohol-aggression relationship.
AB  - The consumption of an intoxicating dose of alcohol increases the likelihood of
      violent behaviour. Three possible mechanisms involving potentiation, inhibition,
      and disorganization of behaviour are presented. The manner in which these three
      effects may be mediated by serotonergic activity is briefly discussed. A more
      extensive review of the serotonin-aggression relationship is then presented.

PMID- 9539179
TI  - Alcohol, aggression and serotonin: metabolic aspects.
AB  - The role of serotonin (5-hydroxytryptamine) in alcohol-induced aggressive
      behaviour is discussed. Considerable evidence exists in support of an association
      between aggression and serotonin deficiency and between aggression and alcohol
      consumption, and it is also known that alcohol consumption exerts major effects
      on serotonin metabolism. These links are synthesized into the serotonin
      deficiency hypothesis of alcohol-induced aggressive behaviour, which postulates
      that individuals susceptible to aggression after alcohol consumption exhibit a
      marked depletion of their brain serotonin rendering them prone to aggression in
      response to environmental or psychological stimuli or situations. This hypothesis
      has already received support from experimental studies in non-aggressive
      subjects, but remains to be examined in those known to be aggressive after
      alcohol consumption.

PMID- 9539180
TI  - The good practice of the police: an alternative approach in dealing with
      offenders who abuse/misuse alcohol.
AB  - The office of constable is taken by declaration and specifically says '...
      prevent all offences against the persons and properties ...'. The police service,
      like many hospitals and particularly casualty units, comes into initial contact
      with a high proportion of society's problems, including those related to people
      who cannot handle alcohol. This results directly or indirectly in a significant
      number of issues affecting social life detrimentally and at a tremendous cost to
      the public purse. These points at some time or another have been adequately
      illustrated by articles or television documentaries. The police service has a
      duty to prevent crime. The author maintains that, through the collaboration of
      the criminal justice agencies and health services, and using a simple approach,
      behaviour could be altered significantly enough to contribute towards a reduction
      in repeat offending and a consequent decline in the use of public funds. The
      author believes that a great number of people, too large to even contemplate
      quantifying, would have a better quality of life, a goal sought by many, and that
      the police service is well placed to participate constructively in the
      rehabilitation of offenders who have a 'drink' problem.

PMID- 9539181
TI  - Alcohol-related crime: the good practice of the Magistrates' courts.
AB  - Alcohol-related crime is an ongoing problem in the court system of England and
      Wales. The Magistrates' Association believes that the system could be improved
      by: (1) the introduction of a new Licensing Act; (2) better control over licensed
      premises; (3) increased training for licensees; (4) more informative training for
      magistrates on the availability and role of alcohol programmes; (5) improved
      enforcement of licensing laws by the police.

PMID- 9539182
TI  - The development of good practice and treatment in the rehabilitation of alcoholic
      and drug-addicted inmates in Her Majesty's prisons.
AB  - This paper describes the philosophy and development of the Substance Abuse
      Treatment Programme (SATP), which is now operated by the Rehabilitation of
      Addicted Prisoners Trust (RAPt) (formerly the Addicted Diseases Trust, ADT) in
      Her Majesty's Prisons Downview, Coldingley, Pentonville, Wandsworth, and Norwich.
      The SATP treats inmates whose chronic alcohol, drug, and gambling addictions have
      been a major contributor to their offending history. Reference to 'addicts' in
      this paper will be deemed to include all of these groups. Inmates participating
      in the programme are referred to as Members. The essential elements of the
      programme are briefly described, as is its outcome.

PMID- 9539183
TI  - A British All-Party Committee view on alcohol and violence.
AB  - The link between alcohol and crime is well-documented and yet alcohol, as a cause
      of crime, is largely ignored when initiatives are developed to tackle crime. In
      recognition of this, the All-Party Group on Alcohol Misuse. a cross-party forum
      for Members of Parliament and House of Lords peers, undertook an Enquiry into the
      link between alcohol and crime. Evidence was received from a wide range of
      organizations, including criminal justice agencies. The Group drew up a report
      summarizing evidence received and putting forward a range of recommendations
      aimed at tackling alcohol-related crime. The report has acted as a stimulus for
      debate around the issues and contributed to a growing acceptance that alcohol
      related crime is an issue that needs addressing.

PMID- 9539184
TI  - Can the gamma-glutamyl transpeptidase isoforms really be utilized in the
      diagnosis of alcoholic liver disease?

PMID- 9539185
TI  - Leptin in overweight postmenopausal women: no relationship with metabolic
      syndrome X or effect of exercise in addition to diet.
AB  - OBJECTIVE: To examine the effect of diet with exercise on serum leptin and
      whether leptin is associated with the metabolic syndrome X in a high risk
      population such as overweight postmenopausal women. STUDY DESIGN AND SUBJECTS:
      121 healthy overweight, postmenopausal women (aged 49-58y, body mass index (BMI)
      25-42 kg/m2) were randomized to: A low-energy-diet, 4.2 MJ/d (n = 51), low-energy
      diet + standardized physical exercise (n=49) or no intervention (control: n=21)
      for 12 weeks, followed by 6 months follow-up without intervention. MEASUREMENTS:
      S-leptin was measured by Radio Immuno Assay (RIA), body composition and fat
      distribution by dual energy X-ray absorptiometry (DEXA) and anthropometry.
      Factors associated with the metabolic syndrome X and sex hormones were measured.
      RESULTS: S-leptin was two-fold higher than in normal-weight postmenopausal women
      and S-leptin was normalized after weight loss induced by the 12-week low-energy
      diet, without any additive effect of the exercise. Of the factors associated with
      the metabolic syndrome X, serum-leptin correlated significantly only with sex
      hormone-binding-globulin and plasminogen-activator-inhibitor-1, whereas factors
      associated with obesity per se correlated significantly with leptin. Changes in S
      leptin correlated with changes in fat tissue mass during the follow-up, but not
      during the intervention. S-leptin at baseline did not correlate with either short
      term or long term weight loss. CONCLUSION: There is no effect of exercise added
      to diet on S-leptin in overweight postmenopausal women. Leptin does not seem to
      be associated with the metabolic syndrome X, but rather with fatness. S-leptin is
      probably associated with both dynamic and static effects of adipose tissue. S
      leptin did not predict weight loss.

PMID- 9539187
TI  - Food advertising on British children's television: a content analysis and
      experimental study with nine-year olds.
AB  - OBJECTIVES: The nature and significance of food advertising during children's
      television was examined in two studies: a content analysis of advertising (Study
      1) and an investigation of the impact of food adverts on the self-perception of
      overweight children (Study 2). PARTICIPANTS: Study 1 monitored 91 h of children's
      broadcasting on four terrestrial and satellite stations in the UK. In Study 2,
      103 children aged 9.75 y viewed two videotaped cartoons containing either food or
      non-food product advertisements. MEASURES: Study 1 used a detailed record of
      advertisement style and content. Study 2 included a self-report measure of
      current state, and measures of self-esteem, dietary restraint, body weight and
      height. RESULTS: Half of the 828 adverts were for food products, 60% of which
      were for breakfast cereals and confectionery/ snacks. Food advertisements used
      significantly more animation, stories, humour and the promotion of
      fun/happiness/mood alteration. In Study 2, significant interactions between
      advertisement type and overweight were observed on ratings of perceived health
      and appetite for sweets. CONCLUSION: While small changes are apparent,
      advertisements during children's television are still dominated by those for
      foods of questionable nutritional value, in a manner designed to engage attention
      and emotional response. That overweight children appeared more influenced by
      their personal enhancement message, suggests the value of further work
      identifying who is most influenced and by what features of advertising.

PMID- 9539186
TI  - A polymorphism in the 5' untranslated region of the human ob gene is associated
      with low leptin levels.
AB  - OBJECTIVE: To search the human ob gene for mutations and evaluate their role in
      massive obesity. DESIGN: Direct mutation screening of the gene and case-control
      association study. Multivariate analyses for evaluation of differences in
      clinical parameters. SUBJECTS: Primary mutation screening: 24 morbidly obese
      subjects (body mass index (BMI) > 40 kg/m2). Association study: 395 unrelated
      morbidly obese subjects (BMI > 40 kg/m2), 121 lean, non-diabetic control
      individuals, 72 women of a random sample with an average BMI 32.5 kg/m2. RESULTS:
      We report the finding of a DNA variant in exon 1 of the human ob gene (A --> G
      substitution, base + 19). This variant showed a prevalence of 62% in our study
      population. Association analyses under different genetic models (dominant, co
      dominant, recessive) showed no significant evidence for an association of this
      variant with BMI. However, obese individuals homozygous for the G-allele showed
      significantly lower leptin concentrations compared to obese patients either
      heterozygous or homozygous for the A-allele after correction for BMI. CONCLUSION:
      Recent linkage studies have shown evidence for linkage of the hsob locus with
      obesity. Our study provides further evidence that a defect in the ob gene in
      linkage disequilibrium with the G-allele of exon 1 might be involved in obesity
      by affecting leptin concentrations.

PMID- 9539188
TI  - Differences in resting metabolic rates of inactive obese African-American and
      Caucasian women.
AB  - OBJECTIVE: To compare resting metabolic rates (RMR) of African-American (n = 25)
      and Caucasian (n = 22) premenopausal (35+/-1 y, Mean +/- s.e.m.) women who are
      obese (95.2+/-2.9 kg, body mass index (BMI) = 34.7+/-0.9, % body fat = 45.2+/
      0.9), inactive and free from metabolic disorders or medications that would affect
      heart rate or RMR. MEASUREMENTS: RMR and respiratory exchange ratio (RER) by
      indirect calorimetry, body composition by plethysmography, maximal aerobic
      capacity (VO2max) and girth measurements. RESULTS: Group mean comparisons were
      made with a Student's t-test or an ANCOVA, which controlled for individual
      differences in body weight and lean body mass (LBM). Significance was set at P <
      0.05. Groups were not significantly different in age, height, weight, BMI, % body
      fat, fat mass, RER, VO2max, resting heart rate, maximal heart rate; or chest,
      waist, hip, arm, thigh or calf circumferences. After adjusting for body weight,
      RMR (I O2/min) for African-Americans (0.254+/-0.007) was significantly lower (9%)
      than for Caucasians (0.277+/-0.008). After RMR (I O2/min) was adjusted for LBM,
      an even larger difference (-12%) persisted for African-Americans (0.250+/-0.008)
      compared to Caucasians (0.281+/-0.008). Predicted RMR (kJ/d) for the African
      Americans was the same as measured RMR, whereas Caucasian women expended about
      13% more energy than predicted. When controlling for LBM, the partial correlation
      between VO2max and RMR was r=0.51 when VO2max was expressed as I/min, and r=0.56
      when VO2max was expressed as ml O2/kg/min, both highly significant (P < 0.000).
      CONCLUSION: The lower prevalence of obesity in Caucasian women may be due in part
      to a higher RMR as well as an under estimation of RMR in weight control therapy.
      Fitness level (VO2max) as well as LBM are significant predictors of RMR for both
      races.

PMID- 9539189
TI  - Liver abnormalities in severely obese subjects: effect of drastic weight loss
      after gastroplasty.
AB  - OBJECTIVE: To examine the factors associated with liver steatosis in severely
      obese subjects and to test the potential reversibility of fatty liver after
      weight loss. DESIGN: Retrospective clinical study. SUBJECT: 528 obese patients
      before bariatric surgery and 69 obese subjects of the initial cohort evaluated
      before and 27+/-15 months after gastroplasty. MEASUREMENTS: Fatty deposition
      (scored as mild, moderate or severe) and inflammatory changes were evaluated in
      liver biopsies; clinical (body mass index (BMI), age, gender, duration of
      obesity) and biological (glucose, triglycerides, liver enzymes) parameters were
      related to histological findings. RESULTS: 74% of the 528 biopsies showed fatty
      change, estimated as mild in 41% of cases, moderate in 32% and severe in 27%. The
      prevalence of steatosis was significantly higher in men than in women (91% vs
      70%, P = 0.001) and in patients with impaired glucose tolerance or type 2
      diabetes compared with nondiabetics (89% vs 69% P = 0.001). The severity of the
      steatosis was associated with BMI (P = 0.002) but not with the duration of
      obesity or the age of the patient. When compared with patients without fatty
      change, those with liver steatosis had significantly higher fasting plasma
      glucose (5.5 mmol/l vs 5.1 mmol/l, P = 0.007) and triglycerides (1.8 mmol/l vs
      1.3 mmol/l, P = 0.002). Mean serum liver enzyme activities (alkaline phosphatase,
      aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma
      glutamyl-transpeptidase (gammaGT) were significantly (P < 0.001) increased in
      patients with fatty change but remained within laboratory reference values. In
      the 69 patients who have been evaluated after a marked weight reduction (-32+/
      19kg), 45% of the biopsies were considered as normal (vs 13% before, P < 0.001)
      while pure fatty change was still observed in 38% of the patients (vs 83% before,
      P = 0.001). However, the severity of the steatosis was significantly (P < 0.001)
      reduced (mild: 62% vs 21%; moderate: 23% vs 37%; severe: 15% vs 42%). In
      addition, a significant increase of hepatitis was observed in 26% of the biopsies
      (vs 14% before, P < 0.05). CONCLUSIONS: Liver steatosis in obese subjects is
      associated with men, diabetic status, BMI, higher fasting glucose and
      hypertriglyceridaemia. Postgastroplasty weight loss reduces liver steatosis, but
      seems to increase the incidence of inflammatory lobular hepatitis.

PMID- 9539190
TI  - Increased estrogen 2-hydroxylation in obese women using oral indole-3-carbinol.
AB  - OBJECTIVE: To investigate whether the dietary phytochemical, indole-3-carbinol
      (13C), influences the level of estradiol 2-hydroxylation in obese women. DESIGN:
      A clinical intervention study involving the ingestion of purified 13C, 400 mg,
      for two months. SUBJECTS: Five healthy, overweight, premenopausal women (age: 35
      47 y, body mass index (BMI): 27-53 kg/m2). MEASUREMENTS: Two estrogen
      metabolites, 2-hydroxyestrone (2OHE1) and estriol (E3), were measured by
      radioimmunoassay in untimed overnight urine samples, before and after ingestion
      of 13C. RESULTS: The ratio of urinary estrogens, 2OHE1/E3, was significantly
      increased in obese women following 13C, reflecting induction of 2-hydroxylation
      in these women. CONCLUSIONS: Obese premenopausal women experience increased
      estrogen 2-hydroxylation in response to the dietary agent, 13C, similar to non
      obese women. This response to 13C may result in a hormonal milieu that helps
      reduce estrogen-dependent cancer risk.

PMID- 9539191
TI  - Effects of surgically induced weight loss on urinary bladder pressure, sagittal
      abdominal diameter and obesity co-morbidity.
AB  - OBJECTIVE: Evaluate the effects of surgically induced weight loss on intra
      abdominal pressure at one year, reflected in urinary bladder pressure, central
      obesity, measured by sagittal abdominal diameter and obesity co-morbidity.
      DESIGN: Prospective, non-randomized trial. SETTING: University Hospital,
      Operating Room, In-patient, Outpatient Clinics. SUBJECTS: Gastric bypass in 15
      severely obese patients. MEASUREMENTS: Patients underwent pre-operative
      assessment of weight, body mass index (BMI), co-morbid history, urinary bladder
      pressure and sagittal abdominal diameter. Patients were reassessed one year after
      gastric bypass with repeat measurement of weight, bladder pressure, and sagittal
      abdominal diameter and assessment of co-morbidity. RESULTS: There were
      significant (P < 0.001) decreases in weight (140+/-8 - 87+/-6 kg), BMI (52+/-3 -
      33+/-2 kg/m2), sagittal abdominal diameter (32+/-1 - 20+/-2 cm), urinary bladder
      pressure (17+/-2 - 10+/-1 cm H2O) and obesity related problems per patient (2.9+/
      0.4 - 1+/-0.2) one year after gastric bypass, with 69+/-4% loss of excess weight.
      CONCLUSIONS: Increased sagittal abdominal diameter is associated with increased
      intra-abdominal pressure which contributes to obesity related co-morbidity.
      Weight loss following gastric bypass decreases abdominal pressure, sagittal
      abdominal diameter and obesity co-morbidity.

PMID- 9539192
TI  - Differences in resting energy expenditure in African-American vs Caucasian
      overweight females.
AB  - OBJECTIVE: The purpose of this study was to examine differences in both resting
      energy expenditure (REE) and respiratory quotient (RQ) between overweight African
      American and Caucasian women of comparable age and body mass index (BMI). DESIGN:
      Cross-sectional. SUBJECTS: REE was assessed in 41 women (22 African-American and
      19 Caucasian) who were recruited to participate in this study. The African
      American women were aged 36.4+/-5.7 y with a BMI of 32.6+/-5.4 kg/m2, and the
      Caucasian women were aged 35.4+/-5.7 y with a BMI of 31.3+/-3.4 kg/m2.
      MEASUREMENTS: Body composition was assessed using dual energy x-ray
      absorptiometry (DEXA). REE was assessed via the dilution technique following an
      overnight fast. RESULTS: REE was lower in African-Americans (7279+/-825 kJ/d)
      compared to Caucasians (7807+/-854 kJ/d) (P = 0.051). Analysis of covariance
      showed that REE remained significantly lower in African-American women after
      correcting for body weight and lean body mass. There was no effect of ethnicity
      on RQ. CONCLUSION: These results indicate that there is a significant difference
      in REE between Caucasian and African-American overweight women. This difference
      in REE may contribute to the higher rates of obesity found in the African
      American population. This difference may also partially explain the smaller
      weight losses typically seen in African-American women when compared to Caucasian
      women enrolled in a weight loss program.

PMID- 9539193
TI  - Bioelectrical impedance analysis to assess body composition in obese adult women:
      the effect of ethnicity.
AB  - OBJECTIVE: To examine whether the accuracy of bioelectrical impedance analysis
      (BIA) to estimate body composition in overweight women is affected by the
      ethnicity of the individuals. DESIGN: Cross-sectional design to compare body
      composition estimated by BIA to body composition measured by dual energy x-ray
      absorptiometry (DEXA), which was the reference method. SUBJECTS: One hundred
      twenty three overweight women participated in this study, of which 43 women were
      African-American (aged 37.2+/-5.6 y; BMI, 32.3+/-4.9 kg/m2) and 80 were Caucasian
      (aged 36.1+/-5.7 y; BMI, 31.9+/-3.5 kg/m2). MEASUREMENTS: Body composition was
      estimated from BIA using both a generalized and an obesity-specific equation.
      These estimations were compared to body composition measured by DEXA, which was
      the reference method. RESULTS: The generalized BIA equation underestimated lean
      body mass (LBM) by 2.6+/-3.1 kg in Caucasian women and 0.4+/-3.2 kg in African
      American women, with the difference between the ethnic groups being significant
      (P < 0.001). The obesity-specific equation underestimated LBM in Caucasians by
      0.9+/-3.1 kg and overestimated LBM in African-Americans by 1.2+/-2.8 kg (P <
      0.001). An ethnic-specific equation is proposed, and cross-validation of this
      equation indicates that it provides a reasonable estimate of body composition in
      overweight women. CONCLUSIONS: The accuracy of BIA to estimate body composition
      appears to be affected by the ethnicity of the individual. Therefore, an ethnic
      specific equation for overweight women is proposed. However, further validation
      of this prediction model in an ethnically diverse population is necessary.

PMID- 9539195
TI  - Influence of duration of obesity on the insulin resistance of obese non-diabetic
      patients.
AB  - OBJECTIVE: To investigate whether duration of obesity has an independent impact
      on insulin resistance. DESIGN: Case-control study. SUBJECTS: 30 non-diabetic
      obese subjects (age, 34+/-12 y, body mass index (BMI), 33.5+/-0.8 kg x m[-2])
      with a range (1-35 y) of self-reported duration of obesity, and 12 age- and
      gender-matched non-obese controls (BMI, 22.1+/-0.6 kg x m[-2]). MEASUREMENTS:
      Oral glucose tolerance (40 g x m[-2]), insulin sensitivity (by the euglycaemic
      insulin clamp technique), and insulin secretion (as the product of post-hepatic
      insulin clearance and plasma insulin concentration). RESULTS: The obese group
      presented hyperinsulinaemia in the basal state and after glucose loading (insulin
      area = 58+/-5 vs 33+/-3 nmol x I[-1] x 2 h, P = 0.005), insulin resistance (M
      value = 37.4+/-4.8 vs 50.6+/-2.6 micromol x min[-1] x kg FFM[-1], P = 0.002), and
      insulin hypersecretion (61.9+/-6.0 vs 33.9 +/- 4.0 nmol x 2 h, P = 0.007);
      endogenous glucose production was similar in the two groups. In the whole
      dataset, insulin resistance was directly related to BMI, the waist-to-hip ratio
      (WHR), endogenous glucose production, insulin secretion, and fasting serum
      triglycerides and uric acid concentrations. When the obese subjects were
      stratified by duration of obesity, insulin resistance was progressively lower
      with longer obesity duration (P = 0.04). When simultaneously adjusting by age,
      gender and BMI, obesity duration was independently associated with greater
      insulin sensitivity (P = 0.003), lower plasma insulin response to oral glucose (P
      = 0.001), and lower fasting and glucose-stimulated insulin release (P = 0.01 for
      both). CONCLUSIONS: In obese subjects with preserved glucose tolerance, duration
      of obesity is associated with better insulin sensitivity irrespective of the
      degree of overweight.

PMID- 9539194
TI  - Effect of exogenous insulin on protein metabolism with differing nonprotein
      energy intakes in Type 2 diabetes mellitus.
AB  - OBJECTIVE: To determine if insulin treatment combined with a generous protein
      intake would normalize whole-body protein kinetics and nitrogen balance in obese
      subjects with Type 2 diabetes mellitus when compared to obese nondiabetic
      subjects: 1) during weight-maintenance and 2) after a very low energy diet
      (VLED). DESIGN: Clinical intervention study of iso- followed by hypoenergetic
      feedings with or without exogenous insulin. SUBJECTS: Sixteen obese subjects with
      a body mass index (BMI) of 39+/-4 kg/m2, with Type 2 diabetes mellitus (three
      men, six women) or without (one man, six women). MEASUREMENTS: Nitrogen flux rate
      calculated from the urine 15N-urea enrichment by using the 60 h oral 15N-glycine
      method, rates of protein synthesis and breakdown calculated from nitrogen flux on
      days 6-8 (and 13-15 in the diabetic subjects) of isoenergetic feeding and days 24
      26 of a 1.9 MJ diet. RESULTS: With insulin therapy: 1) during isoenergetic
      feeding, in the hyperglycaemic diabetic subjects, nitrogen balance was
      significantly less than in the obese controls (-0.6+/-0.6 compared with +1.8+/
      0.9 g N/d, P = 0.037) but became positive (+2.6+/-0.6 g N/d, P < 0.05); nitrogen
      flux decreased and net protein synthesis increased from values different from
      those of the obese controls to values no longer different; 2) during the VLED,
      plasma glucose concentrations < 7 mmol/L were achieved and maintained in all
      diabetic subjects. Nitrogen equilibrium observed in five out of seven obese
      nondiabetic and four out of nine diabetic subjects was associated with no change
      in nitrogen flux from the euglycaemic isoenergetic studies, but with 17% and 23%
      lower rates of synthesis (P < 0.05) and 7% and 15% lower rates of breakdown (NS)
      in nondiabetic and diabetic subjects, respectively. CONCLUSION: Sufficient
      exogenous insulin to near-normalize glycaemia improves the altered protein
      metabolism in hyperglycaemic diabetic subjects during isoenergetic feeding, and
      restores nitrogen equilibrium better than with VLED alone. Protein metabolism is
      more sensitive to the state of diabetes control than is generally appreciated
      'clinically'.

PMID- 9539196
TI  - The influence of socioeconomic status on the incidence and evolution of obesity
      during early adolescence.
AB  - OBJECT: To analyze the influence of socioeconomic status on the prevalence,
      evolution and incidence of obesity between the ages of 12 y and 15 y in Belgium.
      DESIGN: Retrospective cohort study. SUBJECTS: 2607 children from five social
      groups. MEASUREMENTS: The body mass index (BMI) measured during two school
      medical examinations carried out at an interval of two years between the ages of
      12 y and 15 y. RESULTS: Between the ages of 12 y and 15 y the inverse relation
      between social status and the prevalence of obesity is accentuated in girls. The
      increasing divergence between social groups was a result both of the greater
      incidence of new cases of obesity and the reduced improvement rate in obesity
      already present in adolescents of lower social classes. CONCLUSIONS: Social
      inequalities in obesity increase during early adolescence. Preventive measures,
      targeting children of low socioeconomic status, should be put in place at this
      stage of life.

PMID- 9539197
TI  - Behavioral engineering of activity choice in obese children.
AB  - This laboratory study examined whether making sedentary activities contingent
      upon being physically active would increase obese children's physical activity.
      Fourteen obese children aged 8-12 y participated in a baseline session in which
      they had free choice among a variety of sedentary activities and riding a
      stationary bicycle. Children were then randomized to either a contingent group in
      which watching video cassette recorder (VCR) movies and playing video games were
      contingent upon riding the bicycle or a control group in which all physical and
      sedentary activities remained freely available. Contingent group children
      increased physical activity and decreased television activities in comparison to
      the control, even though other sedentary activities remained freely available.
      Findings suggest that highly valued sedentary activities can reinforce physical
      activities and that sedentary activities do not completely substitute amongst
      themselves. The automated system used to make television activities contingent
      upon physical activity has potential for modifying activity in the treatment of
      obesity.

PMID- 9539198
TI  - Controlled trial of hypnotherapy for weight loss in patients with obstructive
      sleep apnoea.
AB  - OBJECTIVE: To assess if hypnotherapy assists attempts at weight loss. DESIGN:
      Randomised, controlled, parallel study of two forms of hypnotherapy (directed at
      stress reduction or energy intake reduction), vs dietary advice alone in 60 obese
      patients with obstructive sleep apnoea on nasal continuous positive airway
      pressure treatment. SETTING: National Health Service hospital in the UK.
      MEASURES: Weight lost at 1, 3, 6, 9, 12, 15 and 18 months after dietary advice
      and hypnotherapy, as a percentage of original body weight. RESULTS: All three
      groups lost 2-3% of their body weight at three months. At 18 months only the
      hypnotherapy group (with stress reduction) still showed a significant (P < 0.02),
      but small (3.8 kg), mean weight loss compared to baseline. Analysed over the
      whole time period the hypnotherapy group with stress reduction achieved
      significantly more weight loss than the other two treatment arms (P < 0.003),
      which were not significantly different from each other. CONCLUSIONS: This
      controlled trial on the use of hypnotherapy, as an adjunct to dietary advice in
      producing weight loss, has produced a statistically significant result in favour
      of hypnotherapy. However, the benefits were small and clinically insignificant.
      More intensive hypnotherapy might of course have been more successful, and
      perhaps the results of the trial are sufficiently encouraging to pursue this
      approach further.

PMID- 9539199
TI  - Ref: Gallstone formation in obese subjects undergoing a weight reduction diet.

PMID- 9539200
TI  - Neoplastic odontogenic epithelial cells express bone sialoprotein.
AB  - Bone sialoprotein (BSP) is synthesized and secreted by bone-, dentine- and
      cementum-forming cells and has been implicated in de novo bone formation and
      mineralization. In this study, we used histological sections of odontogenic
      neoplasms and performed immunohistochemical and in situ hybridization analyses.
      In ameloblastoma, BSP mRNA signals were seen in the neoplastic epithelial cells
      forming nests, strips and islands. BSP deposition was also seen in the stellate
      reticulum of the tumour masses revealed by immunohistochemistry using human BSP
      antibodies. In calcifying epithelial odontogenic tumour, the calcified masses
      demonstrated positive immunoreactivity to the human BSP antibodies, and the
      hybridization signals for BSP were located in the cells near the calcified
      particles. In the calcifying odontogenic cyst, strong BSP signals were seen in
      cells surrounding the characteristic nests of ghost cells, which often calcify
      subsequently. BSP protein was also found in these cells by immunohistochemistry.
      The active expression of BSP in the epithelial elements of the odontogenic
      tumours of adult patients suggests the activation of this matrix protein gene in
      the neoplastic process, and that BSP may play an important role in tumour
      formation and differentiation with respect to pathological calcification.

PMID- 9539201
TI  - An improved method for the simultaneous demonstration of mRNA and esterase
      activity at the human neuromuscular junction.
AB  - The aim of this study was to develop a simple means of studying the distribution
      of mRNA coding for post-synaptic proteins at the human neuromuscular junction. A
      reliable method by which to identify the junctions in tissue sections after in
      situ hybridization was essential. A method is described for combining the
      histochemical demonstration of esterase activity at the neuromuscular junction
      with autoradiographic localization of mRNA by in situ hybridization in the same
      cryostat section of skeletal muscle. The indigogenic esterase method of Strum and
      Hall-Craggs (1982) was modified in such a way that it is able to survive the
      multiple steps involved in in situ hybridization and autoradiography. The
      protocol is simple and reproducible and has been used successfully on sections of
      both rat and human skeletal muscle. To demonstrate the method, sections were
      reacted to reveal esterase activity and were then processed for in situ
      hybridization using a 35S-labelled probe specific for the epsilon-subunit of the
      acetylcholine receptor. The reaction product was retained after the lengthy in
      situ hybridization and autoradiographic procedures. To our knowledge, this is the
      first demonstration of acetylcholine receptor mRNA by in situ hybridization at
      human neuromuscular junctions.

PMID- 9539202
TI  - Type VI collagen in glomeruli of short- and long-term experimental diabetic rats.
AB  - Type VI collagen was revealed by high-resolution immunocytochemistry in renal
      glomeruli from short- and long-term streptozotocin-injected hyperglycaemic rats
      and from their age-matched normoglycaemic controls. The labellings obtained over
      the glomerular basement membrane and the mesangial matrix were assessed by
      quantitative evaluations. The labellings over the glomerular basement membrane
      were low and sparse in the young normoglycaemic animals but became consistent and
      increased in intensity with age and in both the short- and long-term diabetic
      animals. For the mesangial matrix, this was labelled more systematically, and its
      intensity increased with age and in the short-term hyperglycaemic animals. For
      the long-term hyperglycaemic animals, the intensities of labelling resembled
      those of their age-matched controls. These results indicate that type VI collagen
      appears to be a minor constituent of the extracellular matrix of the rat
      glomeruli, rather concentrated in the mesangial area in the young control animal.
      Concomitant with the general modifications of the extracellular matrix occurring
      with age and diabetes, this component increases, but apparently not with the
      length of the hyperglycaemic state.

PMID- 9539203
TI  - Immunohistochemical localization of angiotensin II in the mouse pancreas.
AB  - Previous studies have suggested the presence of a tissue renin-angiotensin II
      system in the pancreas. These studies were based on the observation of several
      key components of the renin-angiotensin II system using molecular biological,
      biochemical and pharmacological approaches. In the present study, angiotensin II
      was localized immunohistochemically in the mouse pancreas using an indirect
      immunoperoxidase-staining technique. The results showed that angiotensin II-like
      immunoreactivity was localized predominantly in the endothelial cells of
      pancreatic blood vessels and the epithelial cells of pancreatic ducts from a
      subgroup of the vessels and ducts. Compared with those found in the pancreatic
      blood vessels and ductal system, a less pronounced immunoreactivity for
      angiotensin II was also observed in the acinar cells and in the smooth muscle
      layers overlying the pancreatic ducts as well as the blood vessels. However, no
      angiotensin II-like immunoreactivity was detected in the islet cells. Taken
      together with previous findings, the present results suggest a local angiotensin
      II-forming system in the mouse pancreas, which may be a significant autocrine or
      paracrine modulator of diverse pancreatic functions, including regulation of
      pancreatic blood flow and pancreatic anion secretion.

PMID- 9539204
TI  - Co-expression of hepatocyte growth factor and its receptor in human prostate
      cancer.
AB  - Hepatocyte growth factor acts differently depending on the organs or tumours
      involved. It may be produced simultaneously with its receptor, c-Met, in several
      types of malignant tumour cells and may exercise an autocrine regulation. To
      analyse the effect of hepatocyte growth factor in human prostate cancer, we
      conducted immunohistochemistry, in situ hybridization and the reverse
      transcriptase polymerase chain reaction. The first two techniques revealed the
      growth factor in prostate cancer cells, and the polymerase chain reaction
      confirmed this expression. c-Met is expressed in prostate cancer cells, but not
      in interstitial cells. Hepatocyte growth factor is expressed in interstitial
      cells, especially in hormone-treated cancer tissue, indicating that the growth
      factor pathway changes with the hormonal status. Low-grade tumours expressed c
      Met at the plasma membrane. Higher grade tumours tended to express it in the
      cytoplasm, suggesting that the role of c-Met as the hepatocyte growth factor
      receptor was blocked in higher grade tumours. The relationship between the growth
      factor and its receptor is thus influenced by hormonal status and differentiation
      in prostate cancer and is not explained simply in terms of autocrine or paracrine
      action.

PMID- 9539205
TI  - DNA strand breaks in ejaculated human spermatozoa: comparison of susceptibility
      to the nick translation and terminal transferase assays.
AB  - The nick translation and terminal transferase assays have been compared to test
      their relative efficiency in detecting DNA breakage in ejaculated human
      spermatozoa. The results have been correlated with the percentage of chromomycin
      A3 positive sperm, a fluorochrome that is indicative of the protamination state
      of sperm. Examination of the ejaculated sperm of 30 subjects revealed that the
      percentage of positivity to the nick translation and terminal transferase assays
      did not differ, even when using different fixatives. It is concluded that the
      inability of the two assays to distinguish the type of DNA damage, as is possible
      in somatic nuclei, is most probably linked to the unique nature of sperm
      chromatin. It is proposed that the presence of the damaged DNA may be the
      remnants of an imperfect spermiogenesis, probably related to an inadequate
      protamine deposition. This is supported by the strong correlation between the
      presence of DNA damage and underprotamination as evidenced by chromomycin A3.

PMID- 9539206
TI  - Histochemical differentiation between nitric oxide synthase-related and 
      unrelated diaphorase activity in the rat olfactory bulb.
AB  - The widely used NADPH-diaphorase reaction for demonstrating neuronal nitric oxide
      synthase is not as specific as previously thought, as it visualizes both a nitric
      oxide synthase-related activity and a nitric oxide synthase-unrelated diaphorase.
      In the present study, we used the rat olfactory bulb as a model to characterize
      the NADPH-diaphorase activity of neuronal nitric oxide synthase histochemically
      in comparison with neuronal nitric oxide-unrelated diaphorase activity. The NADPH
      diaphorase activity of nitric oxide synthase peaked at pH 8 and at Triton X-100
      concentrations of 1-2.5%. It was stable in an acidic environment but was reduced
      in the presence of Triton X-100 and was inactivated by the flavoprotein
      inhibitor, diphenyleneiodonium. It preferred beta-NADPH as the co-substrate to
      alpha-NADPH and alpha-NADH. In contrast, nitric oxide synthase-unrelated
      diaphorase peaked at pH 10, displayed a Triton X-100 optimum at a concentration
      of 1%, was unstable in an acidic environment and used beta-NADPH, alpha-NADPH and
      alpha-NADH to similar extents. Differences in the characteristics between
      neuronal nitric oxide synthase-related and nitric oxide synthase-unrelated NADPH
      diaphorase can be used to increase the specificity of the histochemical nitric
      oxide synthase marker reaction.

PMID- 9539207
TI  - Corneal glycoconjugates: an ultrastructural lectin-gold study.
AB  - The oligosaccharide chains of cell surface and extracellular matrix
      glycoconjugates are essential for the biological properties of these molecules.
      We have, therefore, investigated carbohydrate residues in the rat cornea using
      biotinylated lectin-gold probes. Fixed corneas were removed and embedded in
      Lowicryl HM20 or LR White. Ultrathin sections were incubated in one of the
      lectins: Triticum vulgare (WGA), Canavalia ensiformis (Con A), Griffonia
      simplicifolia (GS-1), Limax flavus (LFA) and Allomyrina dichotoma (Allo A),
      followed by streptavidin-gold, or the sections were incubated in cationic
      colloidal gold. Semi-quantification of gold labelling was determined for corneal
      endothelium, Descemet's membrane, stroma and epithelium from electron
      micrographs. WGA and Con A binding sites were expressed either moderately or
      strongly throughout the cornea, suggesting a preponderance of alpha-mannose and N
      acetylglucosamine residues. A particular concentration of these sugars was found
      in Descemet's membrane. In contrast, GS-1 (specific for alpha-galactose) and Allo
      A (specific for beta-galactose) labelled all regions weakly. Sialic acid
      residues, as defined by LFA labelling and the expression of neuraminidase
      sensitive cationic colloidal gold binding sites, were sparsely distributed
      throughout the stroma, Descemet's membrane and endothelium. In contrast,
      sialoglycoconjugates were found in significant concentrations in the epithelium.
      Electron microscopy proved useful in providing new information on the cellular
      and subcellular localization of these lectin binding sites.

PMID- 9539208
TI  - Dopamine is released spontaneously from developing midbrain neurons in
      organotypic culture.
AB  - While neuronal activity is important in CNS development, little is known of the
      behaviour of the actual neurotransmitters released during this period. None the
      less, indirect evidence has suggested that the neurotransmitter dopamine actually
      has a morphogenic role. This study is the first attempt to monitor directly and
      in real-time, the release of dopamine from midbrain neurons developing as an
      isolated organotypic slice culture. The observed release of dopamine was both
      spontaneous and synchronized and occurred with an average periodicity that is two
      orders of magnitude longer than the characteristic neuronal discharge activity of
      midbrain dopamine cells. Moreover, elevations in the extracellular concentrations
      of dopamine were markedly more prolonged in these and other developing systems
      than in axon terminal regions in mature striatum in which dopaminergic
      innervation is fully established. Thus, dopamine may have an action in developing
      circuits over spatial and temporal scales that vastly exceed those in mature,
      synaptic-like transmission.

PMID- 9539209
TI  - Cholinergic neurons and terminal fields revealed by immunohistochemistry for the
      vesicular acetylcholine transporter. I. Central nervous system.
AB  - Antibodies directed against the C-terminus of the rat vesicular acetylcholine
      transporter mark expression of this specifically cholinergic protein in
      perinuclear regions of the soma and on secretory vesicles concentrated within
      cholinergic nerve terminals. In the central nervous system, the vesicular
      acetylcholine transporter terminal fields of the major putative cholinergic
      pathways in cortex, hippocampus, thalamus, amygdala, olfactory cortex and
      interpeduncular nucleus were examined and characterized. The existence of an
      intrinsic cholinergic innervation of cerebral cortex was confirmed by both in
      situ hybridization histochemistry and immunohistochemistry for the rat vesicular
      acetylcholine transporter and choline acetyltransferase. Cholinergic interneurons
      of the olfactory tubercle and Islands of Calleja, and the major intrinsic
      cholinergic innervation of striatum were fully characterized at the light
      microscopic level with vesicular acetylcholine transporter immunohistochemistry.
      Cholinergic staining was much more extensive for the vesicular acetylcholine
      transporter than for choline acetyltransferase in all these regions, due to
      visualization of cholinergic nerve terminals not easily seen with
      immunohistochemistry for choline acetyltransferase in paraffin-embedded sections.
      Cholinergic innervation of the median eminence of the hypothalamus, previously
      observed with vesicular acetylcholine transporter immunohistochemistry, was
      confirmed by the presence of vesicular acetylcholine transporter immunoreactivity
      in extracts of median eminence by western blotting. Cholinergic projections to
      cerebellum, pineal gland, and to the substantia nigra were documented by
      vesicular acetylcholine transporter-positive punctate staining in these
      structures. Additional novel localizations of putative cholinergic terminals to
      the subependymal zone surrounding the lateral ventricles, and putative
      cholinergic cell bodies in the sensory mesencephalic trigeminal nucleus, a
      primary sensory afferent ganglion located in the brainstem, are documented here.
      The cholinergic phenotype of neurons of the sensory mesencephalic trigeminal
      nucleus was confirmed by choline acetyltransferase immunohistochemistry. A
      feature of cholinergic neurons of the central nervous system revealed clearly
      with vesicular acetylcholine transporter immunohistochemistry in paraffin
      embedded sections is the termination of cholinergic neurons on cholinergic cell
      bodies. These are most prominent on motor neurons of the spinal cord, less
      prominent but present in some brainstem motor nuclei, and apparently absent from
      projection neurons of the telencephalon and brainstem, as well as from the
      preganglionic vesicular acetylcholine transporter-positive sympathetic and
      parasympathetic neurons visualized in the intermediolateral and intermediomedial
      columns of the spinal cord. In addition to the large puncta decorating motor
      neuronal perikarya and dendrites in the ventral horn, vesicular acetylcholine
      transporter-positive terminal fields are distributed in lamina X surrounding the
      central canal, where additional small vesicular acetylcholine transporter
      positive cell bodies are located, and in the superficial layers of the dorsal
      horn. Components of the central cholinergic nervous system whose existence has
      been controversial have been confirmed, and the existence of new components
      documented, with immunohistochemistry for the vesicular acetylcholine
      transporter. Quantitative visualization of terminal fields of known cholinergic
      systems by staining for vesicular acetylcholine transporter will expand the
      possibilities for documenting changes in synaptic patency accompanying
      physiological and pathophysiological changes in these systems.

PMID- 9539210
TI  - Cholinergic neurons and terminal fields revealed by immunohistochemistry for the
      vesicular acetylcholine transporter. II. The peripheral nervous system.
AB  - The peripheral sympathetic and parasympathetic cholinergic innervation was
      investigated with antibodies directed against the C-terminus of the rat vesicular
      acetylcholine transporter. Immunohistochemistry for the vesicular acetylcholine
      transporter resulted in considerably more detailed visualization of cholinergic
      terminal fields in the peripheral nervous system than reported previously and was
      well suited to also identify cholinergic perikarya. Vesicular acetylcholine
      transporter immunoreactivity completely delineated the preganglionic sympathetic
      terminals in pre- and paravertebral sympathetic ganglia, and in the adrenal
      medulla as well as postganglionic cholinergic neurons in the paravertebral chain.
      Cholinergic terminals of sudomotor and vasomotor nerves of skeletal muscle were
      optimally visualized. Mixed peripheral ganglia, including periprostatic and
      uterovaginal ganglia, exhibited extensive preganglionic cholinergic innervation
      of both noradrenergic and cholinergic postganglionic principal neurons which were
      intermingled in these ganglia. Varicose vesicular acetylcholine transporter
      positive fibres and terminals, representing the cranial parasympathetic
      innervation of the cerebral vasculature, of salivary and lacrimal glands, of the
      eye, of the respiratory tract and of the upper digestive tract innervated various
      target structures including seromucous gland epithelium and myoepithelium,
      respiratory epithelium, and smooth muscle of the tracheobronchial tree. The only
      macrovascular elements receiving vesicular acetylcholine transporter-positive
      innervation were the cerebral arteries. The microvasculature throughout the
      viscera, with the exception of lymphoid tissues, the liver and kidney, received
      vesicular acetylcholine transporter-positive innervation while the
      microvasculature of limb and trunk skeletal muscle appeared to be the only
      relevant somatic target of vesicular acetylcholine transporter innervation.
      Vesicular acetylcholine transporter immunoreactivity was particularly useful for
      identification of parasympathetic intrinsic ganglia, and their terminal fields,
      in heart, uterus, and other peripheral organs receiving parasympathetic
      innervation. Extensive vesicular acetylcholine transporter-positive terminal
      fields were apparent in both atrial and ventricular tissues of the heart
      targeting cardiomyocytes as well as cardiac microvessels. Pericardiac brown
      adipose tissue was also supplied by vesicular acetylcholine transporter-positive
      varicose fibres. The enteric ganglia of the myenteric and submucous plexus, their
      synaptic junctions with circular and longitudinal smooth muscle, and terminal
      fields of the lamina propria of the stomach and intestine and of the local
      microvasculature were intensely vesicular acetylcholine transporter positive.
      Vesicular acetylcholine transporter-positive innervation was delivered to the
      exocrine and endocrine pancreas originating from vesicular acetylcholine
      transporter-positive intrapancreatic ganglia. Vesicular acetylcholine transporter
      immunoreactivity in urogenital organs revealed the patterns of terminal
      cholinergic fields arising from the sacral parasympathetic innervation of these
      structures. Components of the cholinergic nervous system in the periphery whose
      existence has been controversial have been confirmed, and the existence of new
      components of the cholinergic nervous system has been documented, with vesicular
      acetylcholine transporter immunohistochemistry. Visualization of vesicular
      acetylcholine transporter will allow documentation of changes in synaptic patency
      during development, in disease, and during changes in neurotransmission
      accompanying injury and dystrophy, in the peripheral nervous system.

PMID- 9539211
TI  - Inhibitory control of somatodendritic interactions underlying action potentials
      in neocortical pyramidal neurons in vivo: an intracellular and computational
      study.
AB  - The effect of synaptic inputs on somatodendritic interactions during action
      potentials was investigated, in the cat, using in vivo intracellular recording
      and computational models of neocortical pyramidal cells. An array of 10
      microelectrodes, each ending at a different cortical depth, was used to
      preferentially evoke synaptic inputs to different somatodendritic regions.
      Relative to action potentials evoked by current injection, spikes elicited by
      cortical microstimuli were reduced in amplitude and duration, with stimuli
      delivered at proximal (somatic) and distal (dendritic) levels evoking the largest
      and smallest decrements, respectively. When the inhibitory postsynaptic potential
      reversal was shifted to around -50 mV by recording with KCl pipettes,
      synaptically-evoked spikes were significantly less reduced than with potassium
      acetate or cesium acetate pipettes, suggesting that spike decrements are not only
      due to a shunt, but also to voltage-dependent effects. Computational models of
      neocortical pyramidal cells were built based on available data on the
      distribution of active currents and synaptic inputs in the soma and dendrites.
      The distribution of synapses activated by extracellular stimulation was estimated
      by matching the model to experimental recordings of postsynaptic potentials
      evoked at different depths. The model successfully reproduced the progressive
      spike amplitude reduction as a function of stimulation depth, as well as the
      effects of chloride and cesium. The model revealed that somatic spikes contain an
      important contribution from proximal dendritic sodium currents up to
      approximately 100 microm and approximately 300 microm from the soma under control
      and cesium conditions, respectively. Proximal inhibitory postsynaptic potentials
      can present this dendritic participation thus reducing the spike amplitude at the
      soma. The model suggests that the somatic spike amplitude and shape can be used
      as a "window" to infer the electrical participation of proximal dendrites. Thus,
      our results suggest that inhibitory postsynaptic potentials can control the
      participation of proximal dendrites in somatic sodium spikes.

PMID- 9539212
TI  - Synaptic numbers across cortical laminae and cognitive performance of the rat
      during ageing.
AB  - In this study, we have investigated the changes in the number of individual
      presynaptic boutons in the neocortex of rats and correlated them with cognitive
      performance. Brown Norway x Fischer 344 F1 hybrid rats, aged from one to 24
      months, were used. Using synaptophysin as a marker for presynaptic boutons, we
      found that in the parietal II region of the neocortex an age-related decrease in
      the density of immunostained punctae representing presynaptic boutons occurred.
      Regression analysis showed that this decline in the number of presynaptic boutons
      correlates with ageing (r=0.495, P<0.05). Interestingly, we found that this age
      related depletion of presynaptic boutons was more intense in the deeper cortical
      lamina, such as laminae V and VI (mean decrease of 18%), than in the superficial
      laminae (mean decrease of 8% in laminae I-IV). Using the Morris water maze test,
      we observed that young rats acquired the task at twice the speed of aged animals
      (48.9 +/- 9.0 s and 91.0 +/- 4.9 s for young and aged animals, respectively).
      Furthermore, at the end of the training period, the aged cohort still showed
      significantly higher escape latencies in the Morris water maze. The present
      findings support the concept that the decline in cognitive performances in ageing
      is related to the loss of synapses in the cerebral cortex.

PMID- 9539213
TI  - Simultaneous quantification of serotonin, dopamine and noradrenaline levels in
      single frontal cortex dialysates of freely-moving rats reveals a complex pattern
      of reciprocal auto- and heteroreceptor-mediated control of release.
AB  - In the present study, a novel and exceptionally sensitive method of high
      performance liquid chromatography coupled to coulometric detection, together with
      concentric dialysis probes, was exploited for an examination of the role of
      autoreceptors and heteroceptors in the modulation of dopamine, noradrenaline and
      serotonin levels in single samples of the frontal cortex of freely-moving rats.
      The selective D3/D2 receptor agonist, CGS 15855A [(+/-)-trans-1,3,4,4a,5,10b
      hexahydro-4-propyl-2H-[1]benzopyrano[3 ,4-b]-pyridin-9-ol], and antagonist,
      raclopride, respectively decreased (-50%) and increased (+60%) levels of dopamine
      without significantly modifying those of serotonin and noradrenaline. The
      selective alpha2-adrenergic receptor agonist, dexmedetomidine, markedly decreased
      noradrenaline levels (-100%) and likewise suppressed those of serotonin and
      dopamine by -55 and -45%, respectively. This effect was mimicked by the
      preferential alpha2-adrenergic receptor agonist, guanabenz (-100%, -60% and 
      50%). Furthermore, the alpha2-adrenergic receptor antagonist, RX 821,002 [2(2
      methoxy-1,4-benzodioxan-2-yl)-2-imidazoline], and the preferential alpha2A
      adrenergic receptor antagonist, BRL 44408 [2-(2H-(1-methyl-1,3
      dihydroisoindole)methyl)-4,5-dihydroimidaz ole], both evoked a pronounced
      elevation in levels of noradrenaline (+212%, +109%) and dopamine (+73%, +85%). In
      contrast, the preferential alpha(2B/2C)-adrenergic receptor antagonist, prazosin,
      did not modify noradrenaline and dopamine levels. RX 821,002 and BRL 44408 did
      not significantly modify levels of serotonin, whereas prazosin decreased these
      levels markedly (-55%), likely due to its alpha1-adrenergic receptor antagonist
      properties. The selective serotonin-1A receptor agonist, 8-hydroxy-2-(di-n
      propylamino)-tetralin (8-OH-DPAT), reduced serotonin levels (-65%) and increased
      those of dopamine and noradrenaline by +100%), and +175%, respectively. The
      selective serotonin-1A antagonist, WAY 100,635 [N-[2-[4-(2-methoxyphenyl)-1
      piperazinyl]ethyl]-N-(2-pyridinyl)cyclo- hexanecarboxamide], which had little
      affect on monoamine levels alone, abolished the influence of 8-OH-DPAT upon
      serotonin and dopamine levels and significantly attenuated its influence upon
      noradrenaline levels. Finally, the selective serotonin-1B agonist, GR 46611 [3-[3
      (2-dimethylaminoethyl)-1H-indol-5-yl]-N-(4-methoxybenzyl)acrylamid e], decreased
      serotonin levels (-49%) and the serotonin-1B antagonist, GR 127,935 [N-[4-methoxy
      3-(4-methylpiperazin-1-yl)phenyl]-2'-methyl-4'-(5-me thyl-1,2,4-oxadiazol-3-yl)
      biphenyl-4-carboxamide], which did not significantly modify serotonin levels
      alone, abolished this action of GR 46611. Levels of dopamine and noradrenaline
      were not affected by GR 46611 or GR 127,935. In conclusion, there is a complex
      pattern of reciprocal autoreceptor and heteroceptor control of monoamine release
      in the frontal cortex. Most notably, activation of alpha2-adrenergic receptors
      inhibits the release of noradrenaline, dopamine and serotonin in each case, while
      stimulation of serotonin-1A receptors suppresses serotonin, yet facilitates
      noradrenaline and dopamine release. In addition, dopamine D2/D3 autoreceptors
      restrain dopamine release while (terminal-localized) serotonin-1B receptors
      reduce serotonin release. Control of serotonin release is expressed phasically
      and that of noradrenaline and dopamine release tonically.

PMID- 9539214
TI  - The effects of excitotoxic lesion of the medial prefrontal cortex on latent
      inhibition, prepulse inhibition, food hoarding, elevated plus maze, active
      avoidance and locomotor activity in the rat.
AB  - Latent inhibition is a measure of retarded conditioning to a previously presented
      nonreinforced stimulus that is impaired in schizophrenic patients and in rats
      treated with amphetamine. In terms of neural substrates, latent inhibition
      depends on the integrity of the nucleus accumbens and the inputs to this
      structure from the hippocampal formation and adjacent cortical areas. Since
      another major source of input to the nucleus accumbens is the medial prefrontal
      cortex, and there are numerous demonstrations that manipulations of this region
      can modify ventral striatal dopamine, we investigated the effects of N-methyl-D
      aspartate lesion to the medial prefrontal cortex on latent inhibition, assessed
      in an off-baseline conditioned emotional response procedure in rats licking for
      water. In addition, the effects of the medial prefrontal cortex lesion were
      assessed on a battery of tasks potentially sensitive to medial prefrontal cortex
      damage, including spontaneous and amphetamine-induced activity, elevated plus
      maze exploration, food hoarding, prepulse inhibition, and active avoidance. The
      lesion decreased hoarding behaviour and increased spontaneous exploratory
      activity in the open field, while exerting only mild effects on amphetamine
      induced activity. Prepulse inhibition, exploration of the elevated plus maze, and
      the acquisition of two-way active avoidance were unaffected by the lesion.
      Likewise, latent inhibition was left intact following the lesion, suggesting that
      neither the destruction of the intrinsic cells of the medial prefrontal cortex
      nor any potential lesion-induced changes in subcortical dopamine, affect latent
      inhibition.

PMID- 9539215
TI  - Induction of Fos-protein in the forebrain and disruption of sensorimotor gating
      following N-methyl-D-aspartate infusion into the ventral hippocampus of the rat.
AB  - Several neuropsychiatric disorders, including schizophrenia, are characterized by
      sensorimotor gating deficits. Prepulse inhibition of the acoustic startle
      response is an operational measure assessing sensorimotor gating and has been
      found to be reduced in schizophrenic patients. Much attention has therefore been
      paid to the neuronal mechanisms underlying the disruption of prepulse inhibition.
      The activity of limbic forebrain structures such as the septohippocampal system,
      the prefrontal cortex, and the nucleus accumbens has been the main focus of
      recent research into the regulation of prepulse inhibition in rats. We here
      provide a functional anatomical picture of forebrain structures probably involved
      in the regulation of prepulse inhibition. Stimulation of the ventral hippocampus
      with a subconvulsive dose of N-methyl-D-aspartate caused a significant and long
      lasting disruption of prepulse inhibition. Immunostaining of the c-Fos protein
      revealed a characteristic pattern of neuronal activity in various forebrain
      areas, including the nucleus accumbens and different frontal cortical areas after
      hippocampal stimulation. Based on the present findings, we conclude that the
      overactivity within a network of cortico-limbic forebrain structures compromises
      the normal processing of sensory stimuli by disrupting a neuronal filter
      mechanism. Interestingly, there is a considerable overlap between the pattern of
      neuronal activity observed in our study and the brain pathology in schizophrenics
      reported in the literature.

PMID- 9539216
TI  - Basolateral amygdala lesions block the disruptive effects of long-term
      adrenalectomy on spatial memory.
AB  - The present study examined, in rats with N-methyl-D-aspartate-induced lesions of
      the basolateral amygdala, the effects of long-term adrenalectomy (i.e. 12-13
      weeks) on memory for spatial and cued learning in a water maze. In sham amygdala
      lesioned rats, adrenalectomy induced impairments in acquisition and retention
      performance for the spatial, but not the cued water-maze task. The
      adrenalectomized rats sustained selective degeneration and death of granule cells
      in the dentate gyrus dorsal blade. Continuous supplementation of the animals'
      drinking water with an extremely low dose of corticosterone (20 microg/ml) did
      not block the retention deficit, but blocked the acquisition deficit and the
      dentate gyrus neurodegenerative changes. The finding that the memory impairments
      and dentate gyrus neurodegeneration are dissociable supports the view that the
      adrenalectomy-induced memory effects are due to the loss of activational effects
      of circulating adrenal hormones at the time of learning. In adrenalectomized rats
      which received corticosterone as well as those which did not, lesions of the
      basolateral amygdala blocked the impairing effects of adrenalectomy on spatial
      learning and memory. However, the basolateral amygdala lesions did not affect the
      neurodegenerative changes in the dentate gyrus. In conclusion, the present
      findings provide further evidence that the basolateral amygdala is involved in
      regulating stress hormone effects on learning and memory.

PMID- 9539217
TI  - Kainate-evoked changes in dystrophin messenger RNA levels in the rat hippocampus.
AB  - Dystrophin and dystroglycan messenger RNAs are expressed in specific brain areas,
      including regions of the cortex and the hippocampus, and in such neurons
      dystrophin has been localized to postsynaptic densities. In the present study we
      examined by in situ hybridization the effect of neuronal activation and
      neurotoxicity induced by kainate and pentylenetetrazole administered in vivo on
      dystrophin and dystroglycan expression in the rat brain. Kainate injection
      resulted in a transient but dramatic decrease in dystrophin transcript levels in
      the dentate gyrus granule cells, neurons not affected by kainate neurotoxicity, 6
      h after injection. There was also a strong, concomitant increase in dystrophin
      messenger RNA levels in the CA3 subfield. At 24-72 h after kainate injection, the
      dystrophin transcript in the dentate granule cells returned to control levels,
      while it decreased gradually in the CA subfields, coinciding with the
      neurodegeneration observed in these areas. Comparable results were obtained with
      pan-dystrophin probes and probes specific to the short, G-dystrophin (Dp71)
      isoform that predominates in the dentate gyrus. This indicates that any
      dystrophin transcript that might be expressed in these areas responds to kainate
      in the same manner. In contrast, kainate insult had no significant effect on the
      dystroglycan messenger RNA levels in these hippocampal areas at 6 h post
      injection. At later times. however, there was a gradual decrease in the
      dystroglycan messenger RNA in those areas which respond to the kainate insult
      with extensive neuronal death. For comparison, seizures which are not associated
      with progressive neurodegeneration were induced by pentylenetetrazole: in this
      situation the dystrophin and dystroglycan messenger RNA levels remained unchanged
      in all areas of the hippocampal formation. Since activation of glutamate
      receptors is thought to be involved in some forms of synaptic plasticity in the
      adult hippocampus, our data indicate that the dystrophin gene behaves as a
      candidate plasticity-related gene responding to glutamate.

PMID- 9539218
TI  - Co-injection of beta-amyloid with ibotenic acid induces synergistic loss of rat
      hippocampal neurons.
AB  - Senile plaques are a pathological hallmark of Alzheimer's disease. The major
      component of senile plaques is beta-amyloid which consists of approximately 4000
      mol. wt of peptide. Accumulating evidence suggests that beta-amyloid may
      represent the underlying cause of Alzheimer's disease. In vitro, beta-amyloid has
      been shown either to be directly neurotoxic or to potentiate neurotoxic effects
      of excitatory amino acids. However, beta-amyloid toxicity in vivo has not always
      been reproducible. In this study, we injected beta-amyloid fragment 1-40 or 25-35
      alone or in combination with a small amount of ibotenic acid, an excitatory amino
      acid, into rat hippocampus, and examined the histological and immunohistochemical
      changes two weeks after injection. Although beta-amyloid alone or ibotenic acid
      alone exerted only minimal degenerating effects on neurons just around the
      injection site, the co-injection of beta-amyloid 1-40 or beta-amyloid 25-35 with
      ibotenic acid produced drastic neuronal loss; the haematoxylin-eosin staining
      revealed that most neurons not only around the injection site but also in distant
      areas including CA1, CA4 and dentate gyrus were depleted. The neuronal loss
      occurred in a dose-dependent manner with respect to ibotenic acid.
      Immunohistochemical analysis showed that beta-amyloid with ibotenic acid induced
      great depletion of microtubule-associated protein-2 immunoreactivity and
      infiltration of astrocytes and microglia on neuronal loss. In addition, some
      apoptotic neuronal death indicated by DNA fragmentation and nucleic condensation
      was observed. Beta-amyloid depositions detected by two different types of anti
      human beta-amyloid antibodies were limited to the injection site. Dizocilpine
      maleate (MK-801), an antagonist for an excitatory amino acid receptor, completely
      inhibited the neuronal death in rat hippocampus. These results suggest that the
      co-injection of beta-amyloid with a small amount of ibotenic acid provides a
      useful model for investigation of the pathogenetic mechanisms leading to
      Alzheimer's disease.

PMID- 9539219
TI  - Phencyclidine and corticosteroids induce apoptosis of a subpopulation of striatal
      neurons: a neural substrate for psychosis?
AB  - Phencyclidine, a non-competitive N-methyl-D-aspartate receptor antagonist and
      indirect dopamine agonist, has neuroprotective properties. Phencyclidine,
      however, can also exert toxic effects and causes degeneration of neurons in the
      retrosplenial cortex. In this paper we demonstrate that acute administration of a
      high dose of phencyclidine to rats, (80 mg/kg), also causes death of a
      subpopulation of striatal neurons. The dying cells exhibited many of the
      morphological and biochemical features of cells undergoing apoptosis as revealed
      by a silver methenamine stain, propidium iodide fluorescence histochemistry and a
      TUNEL procedure. The majority of the dying cells tended to be clustered within
      the dorsomedial aspect of the striatum. The type of striatal cell undergoing
      apoptosis was determined by stereotaxically injecting a colloidal gold retrograde
      anatomical tracer into the major areas of striatal termination prior to the
      administration of phencyclidine. This procedure demonstrated that phencyclidine
      induced striatal apoptosis is almost exclusively limited to striatopallidal
      neurons. A similar series of experiments was conducted to determine whether the
      synthetic corticosteroid, dexamethasone, also induces apoptosis of striatal
      neurons. Corticosteroids are known to be toxic to hippocampal neurons and
      interact with striatal dopamine transmission. Acute administration of
      dexamethasone, (20 mg/kg), induced apoptosis of a subpopulation of striatal
      cells. As was the case with phencyclidine, most of the dexamethasone-induced
      apoptotic striatal cells were striatopallidal neurons located within the
      dorsomedial striatum. The pathology during the early stages of Huntington's
      disease is restricted to an equivalent subpopulation of striatal neurons. Many
      Huntington's patients are extremely psychotic during this stage in the
      progression of the disease. Psychosis is also associated with the acute
      administration of both phencyclidine and dexamethasone to humans. We accordingly
      speculate that the selective loss of striatopallidal neurons in the dorsomedial
      striatum may represent the neural substrate of many forms of psychosis.

PMID- 9539221
TI  - Facilitation of striatal acetylcholine release by dopamine D1 receptor
      stimulation: involvement of enhanced nitric oxide production via neurokinin-2
      receptor activation.
AB  - The regulation of striatal cholinergic function by dopamine D1 receptor
      activation was examined in vivo in urethane-anaesthetized rats with microdialysis
      probes. Extracellular acetylcholine levels were enhanced by activation of D1
      receptors either directly by a striatal application of the D1 receptor agonist
      (+)-SKF-38393 (3 microM) or indirectly by the release of dopamine evoked by
      striatal application of neurotensin (0.1 microM) under D2 receptor blockade. SR
      144190, a new potent and selective non-peptide neurokinin-2 receptor antagonist
      (0.03-1 mg/kg, i.p.), dose-dependently reduced the acetylcholine release induced
      by (+)-SKF-38393 or neurotensin. Furthermore, intrastriatal application of SR
      144190 (1 nM) blocked the increase in acetylcholine release induced by the local
      application of (+)-SKF-38393 (3 microM), neurokinin A (1 microM) or substance P
      (1 microM). Finally, a role for nitric oxide in mediating the effects of D1
      neurokinin-2 receptor activation on acetylcholine release is proposed since local
      infusion of the competitive inhibitor of nitric oxide synthase, N(G)-monomethyl-L
      arginine (0.01-10 microM), blocked the increase in acetylcholine release induced
      by (+)-SKF-38393 (3 microM), neurotensin (0.1 microM) or neurokinin A (1 microM)
      without affecting the enhancing effect of the neurokinin-1 agonist septide (0.1
      microM).

PMID- 9539220
TI  - 3-Nitropropionic acid exacerbates N-methyl-D-aspartate toxicity in striatal
      culture by multiple mechanisms.
AB  - We examined the effects of 3-nitropropionic acid-induced succinate dehydrogenase
      inhibition on neuronal ATP content, N-methyl-D-aspartate-induced neuronal death,
      resting membrane potential, and N-methyl-D-aspartate-induced changes in cytosolic
      calcium concentration ([Ca2+]c) in cultured rat striatal neurons. Exposure of
      cultures to 3 mM 3-nitropropionic acid for 3 h did not cause overt toxicity, but
      reduced ATP content by 35%. Treatment with 3-nitropropionic, or removal of Mg2+
      from the medium, enhanced subsequent N-methyl-D-aspartate toxicity, reducing the
      LC50 from 250 microM to 12 microM or 30 microM, respectively. Even after Mg2+
      removal, enhancement of N-methyl-D-aspartate toxicity by 3-nitropropionic acid
      remained pronounced, with the LC50 further decreasing to 3 microM. The mean
      resting membrane potential of neurons treated with 3-nitropropionic acid was -37
      mV, while that in control neurons was -61 mV. Treatment with 3-nitropropionic did
      not affect baseline [Ca2+]c as determined by fura-2 microfluorimetry. N-methyl-D
      aspartate (30 microM) caused a rapid rise in [Ca2+]c, the initial magnitude of
      which was not affected by 3-nitropropionic acid. However, after a 1-h treatment,
      [Ca2+]c was dramatically higher in 3-nitropropionic acid-treated neurons. This
      increased calcium load was washed out slowly and only partially, although calcium
      in control neurons washed out rapidly and almost completely. These results
      suggest that in striatal neurons, the enhancement of N-methyl-D-aspartate
      toxicity caused by succinate dehydrogenase inhibition may be due to synergism
      between partial relief of the Mg2+ blockade of the N-methyl-D-aspartate receptor
      and other mechanisms, including disruption of neuronal calcium regulation. This
      synergism may be relevant to the neuronal death observed in neurodegenerative
      disorders.

PMID- 9539222
TI  - Functional properties of glycine receptors expressed in primary cultures of mouse
      cerebellar granule cells.
AB  - Expression of the glycine receptor was investigated in membranes prepared from
      primary cultures of mouse cerebellar granule cells and postnatal mouse cerebellum
      using the antagonist [3H]strychnine for ligand binding. Scatchard analysis of the
      binding data obtained from P17 cerebellum showed a single population of binding
      sites (K(D) approximately 6 nM) and [3H]strychnine binding to membranes prepared
      from cultured neurons and P17 cerebellum was found to have the same sensitivity
      to the glycinergic agonists glycine, beta-alanine and taurine. The development of
      [3H]strychnine binding sites in cultured cerebellar granule cells and cerebellum
      showed opposing profiles. [3H]strychnine binding to primary cultures increased
      significantly during the culture period whereas during development in vivo the
      number of binding sites decreased over time and was hardly detectable in the
      adult cerebellum. Release of preloaded D-[3H]aspartate evoked by 40 mM K+ from
      granule cells cultured for seven days was inhibited by glycine by about 50%.
      Beginning after seven days in culture the ability of glycine to inhibit
      transmitter release declined to no inhibition after 17 days in culture.
      Experiments with the non-competitive antagonist, picrotoxinin, showed no blocking
      effect of 150 microM picrotoxinin on the glycine-induced inhibition of
      transmitter release. This contrasted with the inhibitory effect of 100 microM
      picrotoxinin in whole-cell patch-clamp recordings on responses to 500 microM
      glycine (56% block). Furthermore, it was demonstrated that the amplitude of the
      glycine activated peak current had the same size after six to seven days and
      after 16-17 days in culture. Northern blot analysis, and co-injection of
      messenger RNA plus antisense oligonucleotides into Xenopus oocytes revealed
      glycine receptor alpha2 and beta messenger RNAs in the cultured granule cells.
      These findings suggest that granule cells in culture express glycine receptor
      isoforms containing alpha2 picrotoxinin-sensitive and alpha2/beta picrotoxinin
      insensitive receptors.

PMID- 9539223
TI  - Involvement of phosphatase activities in the run-down of GABA(A) receptor
      function in rat cerebellar granule cells in culture.
AB  - Run-down of GABA activated Cl- currents was found when rat cerebellar granule
      cells in culture were studied by the whole-cell patch-clamp technique in the
      absence of ATP in the pipette medium. This event could be prevented, even in the
      absence of ATP, by using the perforated-patch technique or by adding to the
      pipette medium either a blocker of protein tyrosine phosphatase, sodium vanadate,
      or deltamethrin, a blocker of the protein serine/threonine phosphatase
      calcineurin. Conversely, run-down could be partially induced, even in the
      presence of ATP, by blockers of tyrosine kinases. A reduction of GABA(A) receptor
      activity was also found in outside-out membrane patches when ATP was not on the
      membrane inside. The run-down phenomenon involved all three conductance levels
      found in these patches: 11, 20 and 30 pS. In all three cases it was due to a
      reduction of channels' open probability. The single-channel experiments showed
      that also in this case run-down was prevented by either sodium vanadate or
      deltamethrin on the membrane cytoplasmic side. Overall, through relatively
      unphysiological conditions (cells in culture and patch-clamp techniques), the
      study of the run-down phenomenon shows that the tyrosine phosphorylation state of
      GABA(A) receptors is of importance in maintaining it in a proper functional
      state. The data also show that tyrosine phosphorylation state is controlled by a
      protein tyrosine phosphatase, whose activity in turn is blocked via
      serine/threonine phosphorylation.

PMID- 9539224
TI  - Calretinin-immunoreactive neurons in the human thalamus.
AB  - The distribution of the calcium-binding protein calretinin in the thalamus of
      normal human individuals was studied with immunohistochemistry. Calretinin
      immunoreactivity was weak in the geniculate bodies and in nuclei of the ventral
      and posterior groups, moderate in the reticular nucleus and in nuclei of the
      anterior, medial, and lateral groups, and strong in nuclei of the midline group
      and anterior intralaminar nuclei. The mediodorsal nucleus was unique among
      thalamic nuclei because it contained a wide variety of intensely immunostained
      perikarya embedded in a moderately-labelled neuropil. The reticular nucleus
      displayed several small and uniformly distributed neuronal clusters composed of
      immunostained perikarya lying in a moderately-labelled neuropil. Intense and
      uniform immunostaining was observed in all midline nuclei and in the anterior
      intralaminar nuclei, including the paracentral and central lateral nuclei. These
      nuclei, which harboured numerous intensely-stained perikarya lying in a dense
      immunoreactive neuropil, were the most strongly-immunoreactive structures of the
      entire human thalamus. At the level of the posterior intralaminar nuclei, the
      central median nucleus was virtually free of immunostaining whereas the
      parafascicular nucleus was moderately labelled. The nucleus submedius located
      just beneath the central median/parafascicular complex displayed a very intense
      calretinin immunostaining. This study has provided evidence for the presence of
      the protein calretinin in the human thalamus. The pattern of distribution of
      calretinin, as delineated in the present study, suggests that this calcium
      binding protein may participate in various subcortical and cortical thalamic
      systems involved in the modulation of emotional and motivational states.

PMID- 9539225
TI  - Direct evidence for nitric oxide synthase in vagal afferents to the nucleus
      tractus solitarii.
AB  - The anatomical relationship between vagal afferents and brain nitric oxide
      synthase containing terminals in the nucleus tractus solitarii was studied by
      means of anterograde tracing combined with immunocytochemistry and immuno
      electron microscopy. Biotinylated dextran amine was injected into the nodose
      ganglion with a glass micropipette. Four to eight days following the injection,
      regions of the nucleus tractus solitarii containing biotinylated dextran amine
      labelled vagal afferents and those containing nitric oxide synthase
      immunopositive terminals were congruent. Many neurons exhibiting nitric oxide
      synthase immunoreactivity were found within the biotinylated dextran amine
      containing terminal field. However dense labeling of terminals with biotinylated
      dextran amine precluded determination if the terminals were nitric oxide synthase
      immunoreactive. Therefore, we combined degeneration of vagal afferents after
      removal of one nodose ganglion with nitric oxide synthase immuno-electron
      microscopy. Axon terminals that possessed characteristic vesicle clusters and
      were partially or completely engulfed by glial processes were identified as
      degenerating vagal afferents. Degenerating axon terminals comprised 38% of the
      total axon terminals in the nucleus tractus solitarii in a sample of sections;
      and of the degenerating axon terminals, 67% were nitric oxide synthase
      immunoreactive. Nitric oxide synthase immunoreactivity was present in 41% of the
      non-degenerating axon terminals. Prominent staining of dendrites for nitric oxide
      synthase immunoreactivity indicated that much of the nitric oxide synthase in the
      nucleus tractus solitarii is not derived from peripheral afferents. Of the total
      number of dendritic profiles sampled, half were nitric oxide synthase
      immunoreactive. Our data support the hypothesis that nitric oxide or nitric oxide
      donors may be present in primary vagal afferents that terminate in the nucleus
      tractus solitarii. While this study confirms that vagal afferents contain brain
      nitric oxide synthase, it demonstrates for the first time that the majority of
      nitric oxide synthase immunoreactivity in the nucleus tractus solitarii is found
      in intrinsic structures in the nucleus. In addition, our data show that second or
      higher order neurons in the nucleus tractus solitarii may be nitroxidergic and
      receive both nitroxidergic and non-nitroxidergic vagal input.

PMID- 9539226
TI  - Direct evidence of trigeminal innervation of the cochlear blood vessels.
AB  - This paper provides the first detailed description of the trigeminal innervation
      of the inner ear vasculature. This system provides a newly discovered neural
      substrate for rapid vasodilatatory responses of the inner ear to high levels of
      activity and sensory input. Moreover, this discovery may provide an alternative
      mechanism for a set of clinical disturbances (imbalance, hearing loss, tinnitus
      and headache) for which a central neural basis has been speculated. Iontophoretic
      injections of biocytin were made via a glass microelectrode into the trigeminal
      ganglion in guinea-pigs. Tissue for histological sections was obtained 24 h
      later. Labeled fibers from the injection site were observed as bundles around the
      ipsilateral spiral modiolar blood vessels, as individual labeled fibers in the
      interscala septae, and in the ipsilateral stria vascularis. The dark cell region
      of the cristae ampullaris in the vestibular labyrinth was also intensively
      labeled. No labeled fibers were observed in the neuroepithelium of the cristae
      ampullaris or the semicircular canals. These results confirm and localize an
      earlier indirect observation of the trigeminal ganglion projection to the
      cochlea. This innervation may play a role in normal vascular tone and in some
      inner ear disturbances, e.g., sudden hearing loss may reflect an abnormal
      activity of trigeminal ganglion projections to the cochlear blood vessels.

PMID- 9539228
TI  - Acute tolerance associated with a single opiate administration: involvement of N
      methyl-D-aspartate-dependent pain facilitatory systems.
AB  - Mechanisms underlying the development of acute tolerance to the analgesic effect
      of opiates were investigated. In the rat tail-flick test, administration of
      naloxone (1 mg/kg, s.c.) 40 min after heroin (1 mg/kg, s.c.) was shown to induce
      hyperalgesia, indicative of a short-onset, opiate-activated pain facilitatory
      systems masking the opiate analgesia. Pretreatment with the N-methyl-D-aspartate
      receptor antagonist dizocilpine maleate blocked, in a dose-dependent manner, the
      naloxone-induced hyperalgesia and potentiated the heroin-induced analgesia. Using
      a schedule of two successive injections of 1 mg/kg heroin, acute tolerance was
      indicated by a marked reduction (-52%) in analgesia induced by the second dose.
      After pretreatment with dizocilpine maleate, the acute tolerance was abolished
      and the analgesic effects of both injections of heroin were strongly potentiated.
      These observations indicate that acute tolerance appears after the first exposure
      to opiates and stems from opiate activation of N-methyl-D-aspartate-dependent
      pain facilitatory systems.

PMID- 9539227
TI  - A non-pungent resiniferatoxin analogue, phorbol 12-phenylacetate 13 acetate 20
      homovanillate, reveals vanilloid receptor subtypes on rat trigeminal ganglion
      neurons.
AB  - Capsaicin, the vanilloid responsible for the pungent taste of hot peppers, binds
      to receptors found primarily in polymodal nociceptors. Capsaicin initially
      stimulates polymodal nociceptors and subsequently inhibits them from responding
      to a variety of stimuli. This property makes it useful clinically as an analgesic
      and anti-inflammatory compound. There is mounting, albeit indirect, evidence for
      the existence of several subtypes of vanilloid receptors. One such piece of
      evidence comes from studying analogues of capsaicin, such as phorbol 12
      phenylacetate 13 acetate 20-homovanillate. This compound binds to (capsaicin)
      vanilloid receptors on sensory neurons, but unlike capsaicin it is non-pungent
      and does not produce hypothermia. To determine how sensory neurons respond to
      phorbol 12-phenylacetate 13 acetate 20-homovanillate, and to compare these
      responses with those evoked by capsaicin, whole-cell patch-clamp measurements
      were performed on cultured rat trigeminal ganglion neurons. It was found that 63%
      of the neurons held at -60 mV were activated by 3 microM, phorbol 12
      phenylacetate 13 acetate 20-homovanillate, and 87% of these were also activated
      by 1 microM capsaicin. In a given neuron, phorbol 12-phenylacetate 13 acetate 20
      homovanillate, like capsaicin, could activate kinetically distinct inward
      currents. The current-voltage curves characterizing phorbol 12-phenylacetate 13
      acetate 20-homovanillate responses were asymmetric and had reversal potentials at
      -5.8 +/- 6.0 mV and 10.4 +/- 4 mV. The averaged dose-response curves for phorbol
      12-phenylacetate 13 acetate 20-homovanillate were fit to the Hill equation and
      had binding constants (K(1/2)s) of 2.73 microM and 0.96 microM and Hill
      coefficients (ns) of approximately 1 for a rapidly- and slowly-activating
      current, respectively. These parameters are consistent with those obtained from
      binding experiments and calcium-influx experiments on sensory nerves. Repeated
      applications of phorbol 12-phenylacetate 13 acetate 20-homovanillate every 3 min
      caused a complete reduction in the rapidly-activating currents leaving only a
      reduced slowly-activating current. This provides strong evidence for the
      independence of these currents and the existence of subtypes of vanilloid
      receptors. Additional evidence for the existence of receptor subtypes is that 10
      microM capsazepine, a specific and competitive inhibitor of capsaicin-evoked
      responses, did not inhibit the phorbol 12-phenylacetate 13 acetate 20
      homovanillate-induced currents in some neurons and partially inhibited them in
      other neurons. Thus, there are capsazepine-sensitive and capsazepine-insensitive
      subtypes of vanilloid receptors. In summary, we have obtained
      electrophysiological and pharmacological evidence for distinct subtypes of
      vanilloid receptors.

PMID- 9539230
TI  - Periaqueductal gray neurons exhibit increased responsiveness associated with
      audiogenic seizures in the genetically epilepsy-prone rat.
AB  - The ventrolateral periaqueductal gray is implicated as a component of the
      neuronal network for audiogenic seizure. This implication is based on
      immunocytochemical labeling of the proto-oncogene, c-fos, and microinjection
      studies in the severe substrain of genetically epilepsy-prone rats that exhibits
      tonic seizures. The present study examines changes in acoustically evoked
      neuronal responses within the periaqueductal gray in the awake and behaving
      genetically epilepsy-prone rat as compared to normal Sprague Dawley rats. Two
      populations of neuronal response were observed in the periaqueductal gray of both
      genetically epilepsy-prone and normal rats. Most of the neurons exhibited long
      latencies (>10 ms) and lower thresholds, and were more responsive to the acoustic
      stimulus. The remainder of the periaqueductal gray neurons exhibited short
      latencies (<10 ms) and higher thresholds, and exhibited minimal responsiveness to
      the acoustic stimulus. The mean threshold of periaqueductal gray acoustically
      evoked neuronal firing of short-latency neurons was significantly higher than
      normal in the genetically epilepsy-prone rat. The number of acoustically evoked
      action potentials was significantly elevated in the genetically epilepsy-prone
      rat, particularly at the highest acoustic intensity and at a repetition rate of
      1/2 s. In the genetically epilepsy-prone rat, the number of action potentials
      exhibited adaptation (habituation) at 1/s as compared to 1/2 s across stimulus
      intensities. Habituation in normal rats was observed primarily at high
      intensities (95 dB sound pressure level or above). During wild running and tonic
      seizures in the genetically epilepsy-prone rat, periaqueductal gray neurons.
      which had diminished firing rates due to habituation, exhibited a tonic firing
      pattern. Just (1-5 s) prior to the onset of tonic convulsive behaviors, an
      increase in the rate of periaqueductal gray tonic firing was observed. These
      patterns of abnormal neuronal firing suggest that periaqueductal gray neurons may
      be involved in generation of the tonic seizure behavioral component of audiogenic
      seizure in the genetically epilepsy-prone rat, which will need confirmation in
      other audiogenic seizure models.

PMID- 9539229
TI  - Acute neural damage in the rat neocortex in vitro induced by a combination of
      anoxia and mechanical stress.
AB  - To elucidate the mechanisms of neural damage after brain ischemia, rat
      neocortical slices were exposed to anoxia at room temperature for 1 h, and other
      slices were prepared from the neocortical blocks exposed to anoxia at room
      temperature for 1 h. Field potentials elicited by the stimulation of layer IV
      were recorded in supragranular layers in these slices. No clear damage was
      observed electrophysiologically or morphologically in these slices. In contrast,
      a complete loss of the trans-synaptic field potentials and a decrease in the
      density of the cells stained with Neutral Red were elicited by injecting an
      anoxic medium into the neocortical blocks at room temperature for 1 h. In the
      slice preparations, the injection of the anoxic medium failed to reproduce clear
      neural damage, while a combination of mechanical stress and anoxia elicited a
      complete loss of trans-synaptic potentials; this was alleviated by Gd3+ (50
      microM) and D(-)-2-amino-5-phosphonovaleric acid (100 microM). These results
      indicate that a combination of mechanical stress and anoxia produces acute and
      severe neural damage even at room temperature in vitro. The mechanism of the
      damage and the relationship between the neural damage in vitro and in vivo are
      discussed.

PMID- 9539231
TI  - Fas expression on human fetal astrocytes without susceptibility to fas-mediated
      cytotoxicity.
AB  - Fas (APO-1/CD95) is a cell surface receptor, initially identified in lymphoid
      cells, but more recently detected in the central nervous system under pathologic
      conditions. Ligation of the fas receptor by fas ligand or by agonist antibodies
      induces apoptotic cell death in most fas-expressing cells. In the current study,
      using dissociated cultures of human fetal central nervous system-derived cells,
      we detected fas expression on astrocytes but not on neurons. Such expression
      differs from our previous results using cultures of human adult central nervous
      system-derived cells, which demonstrated fas expression on oligodendrocytes but
      not on astrocytes; the oligodendrocytes were susceptible to cell death via this
      pathway. Using multiple assays of cell death, including nuclear propidium iodide
      and TUNEL staining to detect nuclear-directed injury, cytofluorometric propidium
      iodide inclusion, and lactate dehydrogenase release to detect membrane-directed
      injury, we found that fas ligation, however, did not induce cell death in the
      cultured fetal astrocytes. Cytokines that augmented (gamma-interferon) or
      inhibited (interleukin-4) fetal astrocyte proliferation did not alter fas
      expression or resistance to fas ligation. Cells obtained immediately ex vivo from
      human fetal but not from adult central nervous system tissue expressed fas; such
      expression was restricted to astrocytes as assessed by dual-stain
      immunohistochemistry. The fetal central nervous system cells did not express fas
      ligand. Our findings indicate that fas expression on central nervous system cells
      may reflect their state of maturity; expression may not, however, always be
      coupled to susceptibility to cell death via this pathway.

PMID- 9539232
TI  - Unilateral medial temporal lobe memory impairment: type deficit, function
      deficit, or both?
AB  - Previous research has characterized memory deficits resulting from unilateral
      hippocampal system damage as 'material specific', suggesting that left damage
      results in verbal memory impairment with preservation of visuospatial function
      and the converse with right damage. Implicit within this hypothesis are the
      assumptions that the systems are independent and memory is lateralized for each
      type of material. To test the verbal component of this hypothesis, unilateral
      hippocampal lesion and commissurotomy patients were compared with controls on a
      multiple-list free-recall task. The material specific hypothesis predicts severe
      impairment only with left lesions; right lesions and commissurotomy patients
      should be only minimally impaired. However, secondary memory was compromised at
      immediate recall for all patient groups, with both unilateral groups showing
      comparable and severe verbal episodic memory deficits. Final testing across all
      lists also revealed severe impairment in commissurotomy patients. Finding both
      unilateral groups to be similarly impaired for verbal material is taken as
      evidence against a material specific deficit during this verbal episodic memory
      task. Although previous data suggest that left patients are considerably more
      impaired during some verbal tasks, this may not be specific to the material, but
      rather the combination of material and task demands. Implications for the
      material specific hypothesis are discussed.

PMID- 9539233
TI  - Networks of domain-specific and general regions involved in episodic memory for
      spatial location and object identity.
AB  - Positron emission tomography (PET) was used to investigate human episodic memory
      for spatial location and object identity. We measured regional cerebral bloodflow
      (rCBF) while subjects engaged in perceptual matching of the location or the
      identity of line drawings of objects. Perceptual matching also involved
      incidental encoding of the presented information. Subsequently, rCBF was measured
      when subjects retrieved the location or the identity of these objects from
      memory. Using the multivariate partial least squares image analysis, we
      identified three patterns of activity across the brain that allowed us to
      distinguish structures that are differentially involved in processing spatial
      location and object identity from structures that are differentially involved in
      encoding and retrieval but operate across both domains. Domain-specificity was
      evident by increased rCBF during the processing of spatial location in the right
      middle occipital gyrus, supramarginal gyrus, and superior temporal sulcus, and by
      increased rCBF during the processing of object identity in portions of bilateral
      lingual and fusiform gyri. There was a nearly complete overlap between domain
      specific dorsal and ventral extrastriate cortex activations during perceptual
      matching and memory retrieval. Evidence of domain-specificity was also found in
      the prefrontal cortex and the left hippocampus, but the effect interacted with
      encoding and retrieval. Domain-general structures included bilateral superior
      temporal cortex regions, which were preferentially activated during encoding, and
      portions of bilateral middle and inferior frontal gyri, which were preferentially
      activated during retrieval. Together, our data suggest that encoding and
      retrieval in episodic memory depend on the interplay between domain-specific
      structures, most of which are involved in memory as well as perception, and
      domain-general structures, some of which operate more at encoding and others more
      at retrieval.

PMID- 9539234
TI  - Auditory attentional shifts in reading-disabled students: quantification of
      attentional effectiveness by the Attentional Shift Index.
AB  - A controversy has existed for some years regarding auditory attentional skills in
      reading-disabled children. Data have suggested highly developed attentional
      skills in groups of reading-disabled students, but reduced attentional shifts
      have also been documented in equivalent groups. Attentional shifts in dichotic
      listening with forced or directed attention are usually inferred from a
      significant interaction between attentional task and ear. However, this procedure
      cannot be used to evaluate individual test performance, and the interaction does
      not give a useful measure of attentional shifts in dichotic listening meaningful
      for comparison with other tests of attention. In this paper attentional shifts in
      dichotic listening are quantified with the Attentional Shift Index (ASI), a
      measure for evaluating the degree of attentional shift in individual subjects.
      The ASI is based on the log-odds ratio of hits and intrusion errors when the
      subject has been tested under conditions of directed or forced attention. When
      58.3% of the normative sample showed significant attentional shifts, none of the
      reading-disabled sample did so. This finding is discussed in relation to
      different types of deficits that can account for for the lack of auditory
      attentional shifts.

PMID- 9539235
TI  - The effect of complexity upon hemispheric specialization for reading Chinese
      characters.
AB  - A number of reports in the literature have suggested that there is a right
      hemisphere advantage for the processing of single Chinese or Japanese characters.
      There are, nonetheless, many studies which have produced contradictory findings,
      suggesting that the factor or factors underlying the lateral asymmetry have not
      been clearly identified. The present study investigated the proposal that visual
      complexity of single Chinese characters, as measured by stroke number, was
      related to a right hemisphere advantage for processing this material. However,
      increasing the level of complexity of the characters was found to be related to
      the development of a left hemisphere advantage, thus clearly disconfirming the
      proposal. It is argued that the results are more satisfactorily interpreted in
      terms of the relationship between hemisphere specialization and the spatial
      frequency of the stimuli.

PMID- 9539236
TI  - Word reading in Alzheimer's disease: cross-sectional and longitudinal analyses of
      response time and accuracy data.
AB  - Using a list of high- and low-frequency regular and exception words, we measured
      the reading performance of three groups of subjects: patients with mild dementia
      of the Alzheimer's type (DAT) at presentation (Stage 1) and 2-3 years later
      (Stage 2); moderately severe DAT patients; and control subjects. In the
      longitudinally studied patients, there was a dramatic increase in response times
      (RTs) from Stage 1 to Stage 2, but little change in either error rate or pattern.
      By contrast, a comparison of the Stage 2 with the Moderate patients revealed
      similar RTs but a significant increase in error rate for the Moderate group,
      particularly on low-frequency exception words. These two results for word naming
      were almost exactly mirrored by effects in picture naming. We conclude that
      correct word reading, especially for less common words with atypical spelling
      sound correspondences, is compromised in DAT only when the disease produces a
      significant deterioration of semantic memory. These results are relevant to
      current theories about normal and impaired reading processes.

PMID- 9539237
TI  - Selective speech motor, syntax and cognitive deficits associated with bilateral
      damage to the putamen and the head of the caudate nucleus: a case study.
AB  - Deficits in speech production, sentence comprehension and abstract reasoning
      occurred in a subject having profound bilateral damage to the putamen and the
      caudate nucleus. Acoustic analyses indicated that the subject's speech was
      degraded due to inappropriate sequencing of articulatory gestures that involve
      different articulatory structures. Transitions between sounds were slow and often
      did not achieve target configurations. The subject had a 14% error rate
      comprehending distinctions in meaning conveyed by syntax in English sentences;
      normal controls make virtually no errors in this test. Cognitive deficits
      involving impaired sequencing occurred: the subject had a 70% error rate on the
      Odd Man Out test when making decisions within a single category. Cognitive
      perseveration occurred when the subject was asked to shift categories. In
      contrast, performance was within normal ranges in tests of lexical access and
      memory. The pattern of deficits provides evidence for basal ganglia involvement
      in the regulation of sequencing across modalities.

PMID- 9539238
TI  - Growing pains for the environmental genetics of breast cancer: observations on a
      study of the glutathione S-transferases.

PMID- 9539239
TI  - High-grade prostatic intraepithelial neoplasia: additional links to a potentially
      more aggressive prostate cancer?

PMID- 9539240
TI  - NCCN outcomes database makes debut.

PMID- 9539242
TI  - Why tumors travel to certain sites still puzzles researchers.

PMID- 9539243
TI  - Ready, set, go...stop: lessons learned from cancer prevention trials.

PMID- 9539241
TI  - An Icelandic saga: fishing for genes in the North Atlantic.

PMID- 9539244
TI  - Case-control studies of cancer screening: theory and practice.
AB  - This review summarizes methodologic theories for the design of cancer screening
      case-control studies and examines the methods applied in studies published in
      English from 1980 through 1996. In addition to summarizing state-of-the-art
      methodologic approaches, we identify areas where obvious gaps exist between
      theory and practice, and we recommend potential areas where theory and
      methodology may need further development. In particular, we focus on three major
      areas: 1) the selection of case and control subjects, 2) the definition of
      exposure (i.e., exposure to the screening test), and 3) bias. Each area is
      considered carefully by summarizing current theory, reviewing cancer screening
      applications, and linking recommended methodologic approaches to those used in
      practice to identify areas where inconsistencies exist. In general, we found
      methodologic theory and practice in this field of research to be consistent.
      However, discrepancies were identified in the area of exposure definition,
      including the use of screening frequency and the use of a detectable, curable
      preclinical phase for case subjects as the exposure measures. Even when
      recommended methods were followed, a number of difficulties arose in practice.
      Specific concerns included the ability to carry out the following: identifying
      all case subjects within a source population, defining eligibility criteria to
      ensure that case and control subjects had equal access to screening during the
      exposure period, distinguishing between symptomatic and diagnostic tests, and
      controlling for self-selection bias. Careful scrutiny is warranted in all aspects
      of the design of cancer screening case-control studies, and caution is advised in
      the interpretation of study results.

PMID- 9539245
TI  - Relationship between topotecan systemic exposure and tumor response in human
      neuroblastoma xenografts.
AB  - BACKGROUND: Topotecan is a topoisomerase I inhibitor with activity against
      xenografts of childhood solid tumors and established clinical activity against
      neuroblastoma and rhabdomyosarcoma. We have studied the relationship between
      systemic exposure to and the antitumor activity of topotecan lactone (the active
      form of the drug) in the xenograft models. Furthermore, we determined whether the
      responses seen in these models occur at systemic exposure levels that are
      tolerable in children. METHODS: Neuroblastoma xenografts derived from the tumors
      of six different patients were established subcutaneously in immune-deprived
      mice. Topotecan was administered by intravenous bolus injection 5 days a week for
      2 consecutive weeks, repeated every 21 days for three cycles. The minimum daily
      doses that induced complete responses (CRs) and partial responses (PRs) were
      determined. Topotecan lactone pharmacokinetic studies were performed in both
      tumor-bearing and nontumor-bearing mice. RESULTS: The minimum doses associated
      with CRs and PRs in four of the six neuroblastoma xenografts were 0.61 and 0.36
      mg/kg body weight, respectively. The topotecan lactone single-day systemic
      exposures associated with these doses were 88 and 52 ng x hr/mL, respectively.
      There was an approximately sixfold difference in topotecan lactone systemic
      exposure (290 ng x hr/mL versus 52 ng x hr/mL) associated with achieving CRs in
      the least-sensitive and most-sensitive tumors, respectively. CONCLUSIONS:
      Neuroblastoma xenografts are highly sensitive to topotecan therapy, and responses
      in mice are achieved at systemic exposures similar to those that are clinically
      effective and tolerable in children. These results support the concept of
      deriving preclinical data relating systemic exposure to antitumor activity in
      xenograft models. Such data may be valuable in making informed decisions
      regarding the clinical development of new agents.

PMID- 9539246
TI  - Association between glutathione S-transferase M1, P1, and T1 genetic
      polymorphisms and development of breast cancer.
AB  - BACKGROUND: Glutathione S-transferases (GSTs) are encoded by a superfamily of
      genes and play a role in the detoxification of potential carcinogens. In a nested
      case-control study, we investigated associations between genetic variability in
      specific GST genes (GSTM1, GSTT1, and GSTP1) and susceptibility to breast cancer.
      METHODS: In 1989, a total of 32 898 individuals donated blood samples to a
      research specimen bank established in Washington County, MD. Genotypes of blood
      specimen DNA were determined for 110 of 115 women with incident cases of breast
      cancer diagnosed during the period from 1990 through 1995 and up to 113 of 115
      control subjects. Associations between specific genotypes and the development of
      breast cancer were examined by use of logistic regression to calculate odds
      ratios (ORs) and 95% confidence intervals (CIs). RESULTS: The GSTM1 homozygous
      null genotype was associated with an increased risk of developing breast cancer
      (OR = 2.10; 95% CI = 1.22-3.64), principally due to an association with
      postmenopausal breast cancer (OR = 2.50; 95% CI = 1.34-4.65). For GSTP1, the data
      were suggestive of a trend of increasing risk with higher numbers of codon 105
      valine alleles (compared with isoleucine alleles); a 1.97-fold increased risk of
      breast cancer (95% CI = 0.77-5.02) was associated with valine/valine
      homozygosity. The risk of breast cancer associated with the GSTT1 homozygous null
      genotype was 1.50 (95 % CI = 0.76-2.95). The risk of breast cancer increased as
      the number of putative high-risk genotypes increased (P for trend <.001) (OR =
      3.77; 95% CI = 1.10-12.88 for a combined genotype of GSTM1 null, GSTT1 null, and
      either GSTP1 valine heterozygosity or GSTP1 valine homozygosity). CONCLUSIONS:
      Our findings suggest that genetic variability in members of the GST gene family
      may be associated with an increased susceptibility to breast cancer.

PMID- 9539247
TI  - Altered expression of RET proto-oncogene product in prostatic intraepithelial
      neoplasia and prostate cancer.
AB  - BACKGROUND: The RET proto-oncogene encodes a protein that belongs to the tyrosine
      kinase growth factor receptor family. Germline point mutations in RET are found
      in individuals with multiple endocrine neoplasia (MEN) syndromes, and gene
      rearrangements have been reported in papillary thyroid cancers. We recently
      identified transcripts of the RET proto-oncogene in human prostate cancer
      xenografts and prostate cancer cell lines by means of reverse transcription
      polymerase chain reaction analyses. The purpose of this study was to investigate
      Ret protein expression in human prostate tissue. METHODS: Ret protein expression
      was evaluated immunohistochemically in formalin-fixed, paraffin-embedded whole
      prostate sections. The prostate specimens were obtained from 30 patients with
      prostate cancer after radical prostatectomies. Ret protein expression was
      compared in tumor foci and benign prostatic tissue. Medullary thyroid carcinoma
      tissue associated with an MEN syndrome and papillary thyroid cancer tissue served
      as positive controls. RESULTS: Ret appeared to be overexpressed in high-grade
      (histopathologically advanced) prostatic intraepithelial neoplasia (PIN) and
      prostate cancer when compared with its expression level in benign prostatic
      secretory epithelium. In addition, there was an apparent increase in Ret protein
      expression with decreased cellular differentiation, i.e., increasing Gleason
      pattern. CONCLUSION: Expression of the RET proto-oncogene in benign prostatic
      epithelium, high-grade PIN, and histopathologically advanced prostate cancer
      suggests that RET may play a role in the growth of both benign and neoplastic
      prostate epithelial cells.

PMID- 9539248
TI  - UV-radiation-specific p53 mutation frequency in normal skin as a predictor of
      risk of basal cell carcinoma.
AB  - BACKGROUND: A strong association has been found between skin cancer and exposure
      to UV radiation. The p53 tumor suppressor gene (also known as TP53), which is
      frequently mutated in human cancers, is believed to be an early target in UV
      radiation-associated skin carcinogenesis. We have previously developed a
      sensitive, polymerase chain reaction-based method capable of detecting and
      quantifying a UV radiation-specific mutation in the p53 gene (codons 247 and 248:
      AAC CGG --> AAT TGG) in normal skin. We have used this method to examine whether
      UV radiation-specific mutation frequency is associated with risk of basal cell
      carcinoma (BCC) and with sun exposure. METHODS: This case-control study in
      Australia involved 53 case subjects with BCC and 75 control subjects. DNA was
      isolated from normal skin (mirror-image anatomic site to the cancer site for case
      subjects and a randomly selected site for control subjects) and assayed for p53
      mutation. Relationships between p53 mutation frequency and risk of BCC, sun
      sensitivity, or sun exposure were estimated by use of odds ratios (ORs) and 95%
      confidence intervals (95% CIs). RESULTS: Case subjects were more likely to have a
      p53 mutation than control subjects (OR = 3.1; 95% CI = 1.3-7.1). In addition, the
      odds of BCC increased monotonically with increasing frequency of p53 mutation. No
      statistically significant associations could be demonstrated between p53 mutation
      frequency and age, sex, sensitivity to the sun, pigmentary characteristics, total
      lifetime sun exposure, or sun exposure to the biopsy site. CONCLUSIONS: Our
      results indicate that tandem CC --> TT mutations involving codons 247 and 248 of
      the p53 gene are associated with an increased risk of BCC but cannot be used as
      an accurate measure of total UV-radiation exposure.

PMID- 9539249
TI  - Estrogen receptor polymorphism at codon 325 and risk of breast cancer in women
      before age forty.
AB  - BACKGROUND: The estrogen receptor (ER) protein is believed to play a role in the
      development and progression of breast cancer. In a previously published U.S.
      clinic-based study, a polymorphism in the ER gene (codon 325, CCC --> CCG) was
      found to be more common in 34 case subjects with a family history of breast
      cancer than in 154 case subjects without such a history (mean allele frequencies
      +/- standard error = 0.28+/-0.05 versus 0.11+/-0.02; P<.001). To determine
      whether this polymorphism is a risk factor for early-onset breast cancer, we
      conducted a population-based, case-control-family study in Australia. METHODS:
      Case subjects under the age of 40 years with a first primary breast cancer and
      control subjects, frequency-matched to the case subjects on the basis of age, and
      their relatives were interviewed to assess the family history of breast cancer.
      Polymorphism status of the ER gene was determined for 388 case subjects and 294
      control subjects. All statistical tests were two-tailed. RESULTS: There was no
      association between ER gene polymorphism status and breast cancer, before or
      after adjustment for risk factors. There was no difference in allele frequencies
      between case subjects and control subjects (0.232+/-0.015 versus 0.209+/-0.017; P
      = .4) or between women with and without a family history of breast cancer (P =
      .3), irrespective of case-control status. The findings were not altered when
      different definitions of family history of breast cancer were used and when
      allele frequencies were adjusted for residence and country of birth. CONCLUSION:
      We found no evidence that the ER codon 325 polymorphism is associated with breast
      cancer before the age of 40 years or with a family history of breast cancer,
      despite ample power to detect effects half the magnitude of those previously
      reported.

PMID- 9539250
TI  - Telomerase activity in benign and malignant breast lesions: a pilot prospective
      study on fine-needle aspirates.

PMID- 9539251
TI  - Model for the molecular genetic diagnosis of endometrial cancer using K-ras
      mutation analysis.

PMID- 9539252
TI  - Family history of cancer in patients with glioma: a validation study of accuracy.

PMID- 9539253
TI  - Re: Preferential adhesion of prostate cancer cells to a human bone marrow
      endothelial cell line.

PMID- 9539254
TI  - Vitamin D3 enhances mood in healthy subjects during winter.
AB  - Mood changes synchronised to the seasons exist on a continuum between
      individuals, with anxiety and depression increasing during the winter months. An
      extreme form of seasonality is manifested as the clinical syndrome of seasonal
      affective disorder (SAD) with carbohydrate craving, hypersomnia, lethargy, and
      changes in circadian rhythms also evident. It has been suggested that seasonality
      and the symptoms of SAD may be due to changing levels of vitamin D3, the hormone
      of sunlight, leading to changes in brain serotonin. Forty-four healthy subjects
      were given 400 IU, 800 IU, or no vitamin D3 for 5 days during late winter in a
      random double-blind study. Results on a self-report measure showed that vitamin
      D3 significantly enhanced positive affect and there was some evidence of a
      reduction in negative affect. Results are discussed in terms of their
      implications for seasonality, SAD, serotonin, food preference, sleep, and
      circadian rhythms.

PMID- 9539255
TI  - Involvement of central cannabinoid (CB1) receptors in the establishment of place
      conditioning in rats.
AB  - The involvement of cannabinoid processes in positive reinforcement was studied
      using an unbiased, one-compartment, conditioned place preference (CPP) procedure
      in rats. This was achieved by examining the ability of the selective antagonist
      of the CB1 cannabinoid receptor subtype, SR 141716, to counteract the CPP
      supported by classical reinforcers. The acquisition of CPP induced by cocaine (2
      mg/kg), morphine (4 mg/kg) and food (standard chow and sucrose pellets) was dose
      dependently blocked by pre-pairing administration of SR 141716 (0.03-3 mg/kg).
      However, SR 141716 (up to 10 mg/kg) did not significantly counteract the
      expression of cocaine-induced CPP. On the other hand, the synthetic CB receptor
      agonist, WIN 55212-2 (0.3-1 mg/kg), established a robust place aversion (CPA), as
      already described with other agonists, and CPP was never observed, even at 100
      fold lower doses. The aversive effect of WIN 55212-2 was reversed by SR 141716
      (0.3-1 mg/kg), suggesting that it was accounted for by the stimulation of CB1
      receptors. These findings indicate that, on their own, CB receptor agonists are
      unable to generate the processes necessary to induce a pleasurable state in
      animals, as assessed in place conditioning procedures. Nevertheless, a
      cannabinoid link may be involved in the neurobiological events, allowing the
      perception of the rewarding value of various kinds of reinforcers. However, a
      permanent endogenous cannabinoid tone seems unlikely to be necessary to ensure
      the organism a basal hedonic level since, given alone, SR 141716 supported
      neither CPP nor CPA.

PMID- 9539257
TI  - Correlation between plasma clozapine concentration and heart rate variability in
      schizophrenic patients.
AB  - Forty schizophrenic patients treated with 50-600 mg/day of clozapine as
      monotherapy and 40 normal control subjects were tested for heart rate variability
      (HRV) which is mediated by the vagus nerve using acetylcholine as
      neurotransmitter. As compared to the control subjects, the patients showed
      essentially reduced HRV parameters which were negatively correlated with the
      plasma clozapine levels. Therefore, clozapine's anticholinergic effect is
      correlated to the plasma clozapine level when measured by the decrease of HRV. We
      suggest that HRV data might be useful as a predictor for plasma clozapine levels.

PMID- 9539256
TI  - Effects of various factors including the CYP2D6 genotype and coadministration of
      flunitrazepam on the steady-state plasma concentrations of bromperidol and its
      reduced metabolite.
AB  - The effects of various factors, including the cytochrome P450 (CYP) 2D6 genotype
      and the coadministration of flunitrazepam, on the steady-state plasma
      concentrations (Css) of bromperidol and its reduced metabolite were studied in 62
      schizophrenic inpatients receiving bromperidol 12 mg/day. By use of allele
      specific PCR analysis, the wild type allele (CYP2D6*1A) and four mutated alleles
      causing either absent (CYP2D6*3, CYP2D6*4 and CYP2D6*5) or decreased (CYP2D6*10)
      CYP2D6 activity were identified. The means (ranges) of the Css of bromperidol and
      reduced bromperidol corrected to the median body weight were 7.2 (1.3-17.4) and
      2.2 (0.4-8.9) ng/ml, respectively. Neither the Css of bromperidol nor that of
      reduced bromperidol significantly differed among the patients with no (n = 28),
      one (n = 30) and two mutated alleles (n = 4). The patients coadministered with
      flunitrazepam (n = 52) had significantly (P < 0.05) higher Css of bromperidol,
      but not reduced bromperidol, than those not (n = 10). Age, sex and smoking had no
      significant effects on the Css of these compounds. The present study thus
      suggests that the polymorphic CYP2D6 is not involved in the metabolism of
      bromperidol and reduced bromperidol to a major extent. The coadministration of
      flunitrazepam inhibits the metabolism of bromperidol, but age, sex and smoking do
      not affect it.

PMID- 9539258
TI  - Sensitisation of withdrawal signs following repeated withdrawal from a
      benzodiazepine: differences between measures of anxiety and seizure sensitivity.
AB  - Three experiments examined the effect of either withdrawal from diazepam, or
      repeated treatment with the convulsant, pentylenetetrazol (PTZ), on behaviour and
      seizure threshold. The behaviours measured were on the elevated plus maze and in
      the four-plate test; seizure threshold was measured as dose of PTZ infused via
      the tail vein to the first clonic twitch. In experiment 1, we examined the effect
      of either single or repeated withdrawal from diazepam using a procedure in which
      the drug was administered SC in a slow release depot. Three cycles of withdrawal
      from diazepam were compared to a single withdrawal experience. A single
      withdrawal from diazepam following chronic treatment gave rise, 72 h following
      the last dosing, to behavioural changes, suggestive of anxiety, in both tests,
      but did not result in a reduced convulsant threshold. In contrast, repeated
      withdrawal resulted in a reduction in sensitivity in several measures of anxiety,
      but sensitised the mice to the convulsive effects of the PTZ. The unexpected
      failure to find an increased sensitivity to a convulsive agent following a single
      withdrawal from SC diazepam was examined in experiment 2. The seizure threshold
      following a single withdrawal of mice which had received diazepam chronically IP
      in aqueous vehicle was significantly reduced relative to vehicle-treated
      controls, whereas that of animals receiving the same dose SC in oil, was not. It
      is argued that the difference may arise from the animals treated repeatedly with
      IP diazepam unintentionally experiencing repeated withdrawal, since the half-life
      of the drug by this route is short. In experiment 3, repeated sub-convulsant PTZ
      treatment reduced the convulsant threshold (the dose of PTZ required to give rise
      to the first clonic twitch), but had no significant effect on the behavioural
      measures of anxiety compared to a single dose of PTZ or vehicle controls. The
      results suggest that repeated withdrawal from chronic treatments with diazepam
      sensitises mice to convulsant stimuli in a manner resembling the effects of
      repeated administration of sub-convulsant doses of PTZ, but that neither repeated
      PTZ nor repeated diazepam withdrawal results in increased sensitivity to
      anxiogenic stimuli; rather, repeated withdrawal from diazepam may reduce the
      susceptibility of mice to behavioural measures of anxiety.

PMID- 9539259
TI  - Caffeine and visuo-spatial attention.
AB  - The effects of two doses of caffeine (1.5 and 3 mg/kg) on various aspects of
      visual selective attention were investigated in 24 healthy human subjects.
      Specific task conditions were compared to provide measures of selectivity for a
      location in the visual field, of distractibility, of selectivity among response
      alternatives, and of strategic influences. In two out of three tasks, caffeine
      speeded responses significantly. However, these effects did not differ across
      conditions within-task, so there was no indication that they were to due to (a)
      specific effect(s) on one or more of the attentional sub-functions. The results
      suggest that the beneficial effects of caffeine in low-load conditions cannot be
      attributed to reduced distractibility or increased suppression of task-irrelevant
      response tendencies.

PMID- 9539260
TI  - Differential effects of diazepam on anxiety in streptozotocin induced diabetic
      and non-diabetic rats.
AB  - The anxiolytic activity of diazepam (DZP) (0.25-1 mg/kg) was investigated in
      streptozotocin (STZ)-induced diabetic adult Charles Foster albino rats of either
      sex. Diabetes was induced by injecting STZ IP (50 mg/kg; in citrate buffer, pH
      4.5). Experiments were performed 72 h later. The rats were subjected to various
      anxiety paradigms, including the open-field exploratory behaviour, elevated plus
      maze and elevated zero maze behaviours and the social interaction tests. In
      addition, rat brain tribulin activity was also assessed as a biochemical marker
      of anxiety. The results indicate that diabetic rats showed significantly more
      anxiogenic activity in comparison to non-diabetic rats on open-field, elevated
      plus maze, zero maze and social interaction tests. In diabetic rats, brain
      tribulin activity (MAO-A inhibitory component) was significantly increased. DZP
      dose dependently produced anxiolytic activity on the various behavioural
      parameters in non-diabetic rats. DZP (0.5 and 1 mg/kg) partially reversed the
      anxiogenic behaviour of STZ diabetic rats in elevated plus maze and zero maze
      tests. However, in open field behaviour and social interaction tests significant
      anxiolytic activity was observed only at a higher dose of DZP (1 mg/kg). The
      findings indicate that STZ-induced diabetic rats exhibited augmented anxiety on
      various experimental paradigms and that the anxiolytic effect of diazepam was
      less marked in diabetic rats as compared to their euglycaemic counterparts.

PMID- 9539261
TI  - An active metabolite of carbamazepine, carbamazepine-10,11-epoxide, inhibits ion
      channel-mediated catecholamine secretion in cultured bovine adrenal medullary
      cells.
AB  - We have recently reported inhibitory effects of carbamazepine (CBZ) on ion
      channel-mediated secretion of catecholamines in bovine adrenal medullary cells.
      Here, we report the effects of carbamazepine-10,11-epoxide (CBZ-E), an active
      metabolite of CBZ, and carbamazepine-10,11-diol (CBZ-D), a non-active metabolite,
      on 22Na+ influx, 45Ca2+ influx and catecholamine secretion in cultured adrenal
      medullary cells. CBZ-E, but not CBZ-D inhibited 22Na+ influx, 45Ca2+ influx and
      catecholamine secretion induced by carbachol or veratridine with a half-maximal
      inhibitory concentration (IC50) of 0.26 or 0.68 microg/ml, respectively. CBZ-E
      also inhibited high K+-evoked 45Ca2+ influx and catecholamine secretion (IC50 =
      0.3 microg/ml), but CBZ-D did not. These findings suggest that CBZ-E, but not CBZ
      D, attenuates catecholamine secretion by inhibiting nicotinic acetylcholine
      receptor-associated ion channels, voltage-dependent Na+ channels and voltage
      dependent Ca2+ channels in the cells. This inhibition of CBZ-E as well as CBZ may
      be related to the clinical effects in neuropsychiatric disorders.

PMID- 9539262
TI  - Duration of sensitization to the locomotor stimulant effects of ethanol in mice.
AB  - Behavioral sensitization to the psychomotor stimulant effects of some drugs can
      be quite persistent, lasting for weeks to months after cessation of drug
      exposure. We investigated the duration of sensitization to the locomotor
      stimulant effects of 2.0 g/kg ethanol (EtOH) and determined whether repeated EtOH
      administration would lead to alterations in blood EtOH clearance rates. Female
      mice were injected (IP) daily for up to 10 consecutive days with saline or EtOH.
      Baseline activity and acute EtOH locomotor responses were evaluated in Omnitech
      automated activity monitors (10-min test), with horizontal distance traveled as
      the measure of locomotion. Locomotor activity response to EtOH was reevaluated
      immediately after the final daily EtOH injection, and at 5-day intervals during
      which no EtOH was administered. Tail blood samples for determination of blood
      ethanol concentrations (BECs) were collected from EtOH-treated mice at the end of
      activity sessions. Sensitization lasted for up to 29 days, and in two of three of
      the behavioral sensitization studies, repeated EtOH treatment resulted in
      elevated BECs. There was no significant effect of repeated EtOH exposure on EtOH
      clearance rate in a study involving no behavioral testing. The demonstration of
      persistent behavioral sensitization may imply a lasting hypersensitivity of
      certain neural pathways to EtOH, thus increasing the reinforcing value of EtOH
      and the probability of relapse to EtOH drinking after abstinence.

PMID- 9539263
TI  - The role of 5-HT receptor subtypes in the anxiolytic effects of selective
      serotonin reuptake inhibitors in the rat ultrasonic vocalization test.
AB  - We evaluated whether the anxiolytic effects of selective serotonin reuptake
      inhibitors (SSRIs) in the rat ultrasonic vocalization (USV) test are
      preferentially mediated by (indirect) activation of 5-HT1A, 5-HT1B/1D, 5-HT2A, 5
      HT3 or 5-HT4 receptors. The SSRIs, paroxetine (ED50 in mg/kg, IP: 6.9),
      citalopram (6.5), fluvoxamine (11.7) and fluoxetine (> 30), dose dependently
      reduced shock-induced USV. The effects of paroxetine (3.0 mg/kg, IP) were not
      blocked by the selective 5-HT1A receptor antagonist, WAY-100635 (3.0 mg/kg, IP),
      the 5-HT1B/1D receptor antagonist, GR 127935 (30 mg/kg, IP), the nonselective 5
      HT2A receptor antagonists, ritanserin (3.0 mg/kg, IP) and ketanserin (1.0 mg/kg,
      IP), the 5-HT3 receptor antagonist, ondansetron (0.1 mg/kg, IP), or the 5-HT4
      receptor antagonist, GR 125487D (3.0 mg/kg, SC). In contrast, the selective 5
      HT2A receptor antagonist, MDL 100,907 (0.1 mg/kg, IP), completely prevented the
      paroxetine-induced reduction of USV. Under similar conditions, WAY-100635 blocked
      the anxiolytic-like effects of the selective 5-HT1A receptor agonist, 8-OH-DPAT
      [(+/-)-8-hydroxy-2-(di-n-propylamino)tetralin, 1.0 mg/kg, IP], and ritanserin,
      ketanserin, and MDL 100,907 blocked the anxiolytic-like effects of the mixed 5
      HT2A/2C receptor agonist, DOI [1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane, 3.0
      mg/kg, IP]. WAY-100635 (1.0 mg/kg, IP) in combination with ritanserin (3.0 mg/kg,
      IP), but not ondansetron (0.1 mg/kg, IP), GR 125487D (3.0 mg/kg, SC), or GR
      127935 (30 mg/kg, IP), attenuated the USV reducing effects of paroxetine.
      Although the results suggest that selective stimulation of 5-HT1A and 5-HT2A
      receptors produces a decrease of USV, we postulate that only 5-HT2A receptors
      play a pivotal role in the effects of SSRIs in this model of anxiety.

PMID- 9539264
TI  - Comparative characterisation of the discriminative stimulus properties of
      clozapine and other antipsychotics in rats.
AB  - The discriminative stimulus properties of the prototypical atypical neuroleptic
      clozapine (5 mg/kg, IP) were characterised in rats using a fixed ratio assay.
      Clozapine induced full dose-related generalization in the absence of response
      suppression. Amphetamine and pentylenetetrazol failed to generalise at doses
      known to be discriminable, showing a degree of specificity for the clozapine cue.
      The typical neuroleptics haloperidol and loxapine induced minimal (20%)
      generalization at doses with marked behavioural effects; thus clozapine
      discrimination dissociates clozapine from typical neuroleptics. Atypical
      neuroleptics which are not clozapine congeners produced weak partial
      generalization when tested up to the highest doses that could be studied. The
      maximal levels of generalization induced by these agents were: amisulpiride 28%,
      risperidone 40% and sertindole 50%. Clozapine congeners typically caused more
      generalization, the novel pyridobenzoxapine JL13 inducing 70% maximal
      generalization. Most generalization (83%) was seen with the clozapine congener
      seroquel, although in contrast to clozapine, it only generalised at doses with
      marked effects on responding, so that no drug mimicked clozapine fully.
      Surprisingly, the clozapine congener olanzapine only induced a maximal level of
      38% generalization. This apparently anomalous finding is attributed to an
      inability to test high doses of the drug due to its rate-suppressant actions. The
      clozapine cue can be used to rank atypical neuroleptics in terms of their
      similarity to clozapine in vivo. The clozapine cue is probably a compound cue,
      since only agents showing "polyvalent" receptor pharmacology induced substantial
      generalization.

PMID- 9539265
TI  - Repeated administration of amphetamine induces sensitisation to its disruptive
      effect on prepulse inhibition in the rat.
AB  - Male Sprague-Dawley rats were repeatedly treated with amphetamine (AMP, 1 mg/kg,
      SC) at 3- day intervals for 15 days and tested for prepulse inhibition of
      acoustic startle after each treatment. This treatment regimen induced
      sensitisation in the animals as evidenced by a progressive increase in the
      disruptive effect of AMP on prepulse inhibition. Persistent changes in brain
      function was indicated, since an increase in disruptive effect was observed in
      sensitised animals also after a 22-day-long drug- and test-free period. The
      development of sensitisation was blocked by pretreatment with haloperidol (HPD,
      0.1 mg/kg, SC), which suggests that sensitisation to the disruptive effect of AMP
      was dependent on dopamine (DA) D2 receptor activation. Furthermore, the
      development of sensitisation was blocked by adrenalectomy, which suggests that
      sensitisation was dependent also on circulating adrenal hormones. Increased DA
      ergic activity has been implicated in the pathophysiology of schizophrenia and
      AMP-induced sensitisation to the neuronal functions that modulate prepulse
      inhibition may be an experimental model to investigate this hypothesis.

PMID- 9539266
TI  - Enhanced delayed matching performance in younger and older macaques administered
      the 5-HT4 receptor agonist, RS 17017.
AB  - Recent evidence indicates that the 5-HT4 subtype of serotonin receptor may
      modulate central cholinergic activity in regions of the mammalian CNS important
      to memory such as the frontal cortex, hippocampus and amygdala. These receptors
      could represent targets for drugs designed for the symptomatic therapy of
      Alzheimer's disease (AD) and other disorders of memory. In the present study, the
      binding activity of RS 17017 (previously described as a selective 5-HT4 agonist)
      was assessed across a number of neurotransmitter receptors and binding sites,
      pharmacokinetic data were obtained, and the compound was evaluated in macaques
      for mnemonic effects via a computer-assisted delayed matching-to-sample task
      (DMTS). Binding data confirmed the 5-HT4 selectivity of the compound, while
      pharmacokinetic results revealed low oral bioavailability, but a large volume of
      distribution of the compound. Significant and reproducible improvements in DMTS
      accuracy were observed after oral administration of the compound across a dose
      effect series in both younger and older monkeys. The results suggest that RS
      17017 offers a potential for memory enhancement in disorders involving cognitive
      decline, and are consistent with a role for central 5-HT4 receptors in memory.
      Improvements in DMTS performance in aged monkeys may have particular implications
      for neurodegenerative conditions such as AD, whereas positive results in the
      younger monkeys indicate that RS 17017 (or similar compounds) may have additional
      potential in the therapeutics of memory disorders not necessarily associated with
      advanced age.

PMID- 9539267
TI  - Pre-exposure of rats to amphetamine sensitizes self-administration of this drug
      under a progressive ratio schedule.
AB  - Two groups of male rats were tested to determine whether pre-exposure to d
      amphetamine would enhance the motivation to self-administer the drug under a
      progressive ratio schedule of reinforcement. In the first phase of the
      experiment, one group of rats received d-amphetamine (2 mg/kg IP), while a second
      group received saline on alternate days for a total of ten injections. Following
      a 21-day drug withdrawal period, behavioral sensitization was confirmed by a
      significant increase in amphetamine-induced stereotypy in the d-amphetamine
      pretreated group, relative to the saline-pretreated group. In the second phase of
      the study, all rats were implanted with chronic jugular catheters and trained to
      self-administer d-amphetamine (0.2 mg/kg per infusion) under a fixed-ratio
      schedule of reinforcement. The progressive ratio paradigm was then imposed for 7
      consecutive days; d-amphetamine-pretreated rats attained significantly higher
      break points than saline-pretreated animals. These data suggest that pre-exposure
      to d-amphetamine may enhance the motivation to self-administer this drug.

PMID- 9539268
TI  - Generalization of a restraint-induced discriminative stimulus to cocaine in rats.
AB  - The ability of the interoceptive cues produced following exposure to restraint
      stress to generalize to the discriminative stimulus effects of cocaine was
      investigated. Rats were trained to discriminate cocaine (10 mg/kg, IP, n=10; or
      20 mg/kg, IP, n=6) from saline using a two-choice, food-reinforced, drug
      discrimination design. Substitution for the 10 mg/kg training dose of cocaine was
      observed subsequent to exposure to 15 min of restraint when administered
      immediately following an injection of saline. Restraint-induced generalization in
      the 20 mg/kg training group was substantial, but not statistically significant.
      These data suggest that a component of the subjective effects of cocaine may be
      associated with "anxiety".

PMID- 9539269
TI  - Hyperprolactinemia; etiology, diagnosis and treatment alternatives.

PMID- 9539270
TI  - Strenuous working conditions and birthweight, Norway 1989.
AB  - OBJECTIVE: To examine whether strenuous working conditions in pregnancy are
      associated with reduced birthweight. METHOD: Cross-sectional, population based
      study. Retrospective data collection by questionnaire to parturients in all
      maternity wards in Norway 16.10-26.11.89, completed before discharge from
      hospital, with response rate 87.2%. The study population consists of the 5388
      women with singleton births, of whom 3321 were in paid work beyond the third
      month of pregnancy. Main outcome measures are prevalence of birthweight <2500
      grams (LBW) and mean birthweight. RESULTS: Strenuous working conditions increased
      risk of LBW, but only for nullipara, particularly non-smoking nullipara. Odds
      ratios with 95% confidence intervals for non-smoking nullipara, adjusted for age,
      education and income, were 0.3 (0.1,0.9) for influence on work pace, 2.8
      (1.2,6.5) for exposure to heavy lifting and 2.2 (0.8,5.8) for twisting/bending.
      Four groups of occupations were defined according to exposure, solely based on
      reports from mothers with non-LBW children in order to avoid recall bias.
      Prevalence of LBW increased from 0.8% in the least exposed to 8.3% in the most
      exposed group. (Test for trend: p<0.05, after adjustment for age, education and
      income.) Strenuous working conditions had no independent effect on mean
      birthweight after adjustment for age, education, income and smoking. CONCLUSION:
      Strenuous work increased the risk of LBW in nulliparae, particularly in non
      smokers. Lack of influence on work pace was the strongest risk factor. The
      preventive effect of job modification in pregnancy may parallel smoking
      cessation.

PMID- 9539271
TI  - Idiopathic thrombocytopenic purpura in pregnancy.
AB  - OBJECTIVE: The aim of this study was to evaluate retrospectively our strategies
      in monitoring and treating pregnant women with idiopathic thrombocytopenic
      purpura (ITP). METHODS: Medical records were reviewed for diagnosis, clinical
      course, treatment, and neonatal outcome in 35 Finnish women with ITP giving birth
      to 55 neonates during 53 pregnancies. The outcome of the first (i.e. index)
      pregnancy was used in the statistical analyses. The platelet immunofluorescence
      test (PIFT) was used for detection of platelet autoantibodies. The correlation
      between neonatal platelet counts and results of PIFT was calculated with the
      Pearson's correlation coefficient and the Fisher's exact test. RESULTS: There
      were no serious bleeding complications although five of 35 women had platelet
      counts of less than 50 x 10(9)/l in the third trimester of the index pregnancy.
      Prophylactic platelet transfusions were given to six of 15 women delivered by
      cesarean section. Five of 35 (14.3%; 95% confidence interval, 2.6 to 25.8%)
      neonates had platelet counts of less than 50 x 10(9)/l median 3 days after
      delivery versus only one of 28 (3.6%; 95% confidence interval, 0.1 to 10.5%) at
      birth. No infant showed any clinical signs of intracranial hemorrhage. No
      significant correlation was encountered between neonatal thrombocytopenia and
      maternal platelet autoantibodies. The history of a previous infant with
      thrombocytopenia was the only important information in estimating the risk of
      fetal thrombocytopenia. CONCLUSIONS: To avoid unnecessary and possibly harmful
      monitoring and treatment, we need further tests for predicting the perinatal
      risks in pregnant women with ITP.

PMID- 9539272
TI  - Leptin levels in pregnancy: marker for fat accumulation and mobilization?
AB  - BACKGROUND: Leptin, an adipose tissue-derived signalling factor encoded by the
      obese gene has been shown to be present as a 16-kDa protein in the blood of mice
      and humans. Resistance to leptin occurs in human obesity. Leptin has also been
      shown to associate with plasma insulin concentrations and there is currently
      considerable debate about the potential link between insulin resistance and
      resistance to leptin. In non-pregnant individuals, circulating leptin
      concentrations associate strongly with both total body fat mass and body mass
      index (BMI). In normal human pregnancy, the maternal fat stores increase to a
      peak in the late second trimester, before declining towards term as fat stores
      are mobilized to support the rapidly growing fetus. Insulin resistance increases
      during late pregnancy and is believed to be further enhanced in pregnancies
      complicated by pre-eclampsia. The aim of this study was to examine if leptin
      levels were altered in pregnancy and, if so, whether the pattern of change in
      circulating leptin related to previously established changes in fasting insulin
      concentrations or fat mass. METHODS: We measured third trimester plasma leptin
      concentrations in 12 uncomplicated pregnant women, nine women with pre-eclampsia
      matched for age and booking BMI, and 18 non-pregnant women similarly matched. We
      also examined the longitudinal course of leptin concentrations occurring
      throughout gestation (from 10 weeks gestation and at five week intervals
      thereafter), in five normal pregnancies and two women with gestational-onset
      diabetes. RESULTS: Leptin concentrations were significantly higher in the normal
      pregnant women (37.1 microg/L, [15.4-117.0], geometric mean, [range]; p=0.049),
      and women with pre-eclampsia (45.3 microg/L, [21.3-98.4]; p=0.001), than in non
      pregnant controls (17.85 microg/L, [1.3-36.5]), however, there was no significant
      difference between uncomplicated and pre-eclamptic pregnancies (p=0.22). On
      examination of the longitudinal course of leptin concentrations occurring
      throughout gestation, in all seven women plasma leptin concentrations initially
      increased relative to booking (10 weeks) concentrations, but did so by varying
      amounts (ranging between 30-233%). Significantly, however, in all seven women
      plasma leptin concentrations peaked at around 20-30 weeks of gestation before
      declining towards term. CONCLUSION: On the basis of these observations, we
      postulate that plasma leptin levels increase significantly in human pregnancies
      and that the pattern of change in circulating leptin parallels the process of fat
      accumulation and mobilization.

PMID- 9539273
TI  - Metabolic control and pregnancy outcome among women with insulin-dependent
      diabetes mellitus. A twelve-year follow-up in the country of Jamtland, Sweden.
AB  - OBJECTIVE: To assess metabolic control and pregnancy outcome in women with
      insulin-dependent diabetes mellitus (IDDM) in a defined rural area of Sweden and
      to compare results for three four-year periods (1982-85, 1986-89, 1990-93).
      MATERIAL AND METHOD: All pregnancies in women with IDDM during the 12-year
      period, 1982-93, received their antenatal care from a 'diabetic team' at the
      County Hospital, Ostersund. There were 50 women in the series, accounting for a
      total of 91 pregnancies. Spontaneous or induced abortions occurred in 19 cases.
      Case notes from maternity, neonatal and pediatric care were retrospectively
      scrutinized. RESULTS: In period one 31% of the pregnancies occurred in gravidae
      with diabetes classified as White D, F or R, as compared with 46% and 71% during
      periods two and three (p=0.001). Maternal hypertension was also more frequent in
      period three (12%, 26% and 54%, respectively; p=0.001). Fewer antenatal
      admissions (p=0.02) but more frequent ultrasound scannings (p=0.014) were
      recorded for period three. HbA1c levels decreased continuously from prepregnancy
      through first and third trimesters (9.7%, 8.4%, and 7.4%, respectively;
      p<0.0001). Perinatal mortality and frequencies of congenital malformations were
      both 4.2% (95% CI 0.5-8.8%), whereas the miscarriage rate was 14.3% (95% CI 6.8
      21.8%). CONCLUSIONS: As compared with the first 4-year period, 1982-85, the third
      period, 1990-93, was characterized by a greater proportion of gravidae with more
      serious diabetes and a higher rate of pregnancy complications, though the outcome
      was nonetheless good, suggesting the diabetic pregnancy care program to have been
      efficacious.

PMID- 9539274
TI  - Four-quadrant assessment of gestational age-specific values of amniotic fluid
      volume in uncomplicated pregnancies.
AB  - BACKGROUND: The purpose of this study was to establish a normative scale of
      amniotic fluid index (AFI) throughout gestation in uncomplicated singleton
      pregnancies, and to identify the lower and upper limits for each gestational
      week. METHODS: Four-quadrant assessment of amniotic fluid volume (AFV) was
      performed prospectively in 750 uncomplicated pregnancies between 16 and 43 weeks.
      The logarithmic transformations were used to get the data in Gaussian
      distribution. The means, and the 90%, 95% and 98% confidence intervals at each
      week of gestation were calculated from polynomial regression equation.
      Statistical differences in AFIs among gestational age groups were tested.
      RESULTS: The amniotic fluid index observations from regression equation curve
      were stratified in week-specific normative curve. The variations between mean AFI
      of the total population and the means of the preterm, term and postdate
      pregnancies were statistically significant (p<0.0001). The 90%, 95% and 98%
      confidence limits about the mean (12.5 cm) were 5.4 to 20.6, 4.2 to 22.3, 1.8 to
      25.8 cm, respectively in term gestation. The 5th and 95th percentile serves as
      lower and upper limits of normal, respectively. CONCLUSIONS: Gestational age
      specific values of AFI were established, determining the significant trends of
      changes in the AFV with gestation. The normogram may have a clinical benefit to
      accurate, reliable and semiquantitative diagnosis of oligohydramnios and
      polyhydramnios.

PMID- 9539275
TI  - Insulin-like growth factor binding protein-1, a quick way to detect amniotic
      fluid.
AB  - BACKGROUND: The detection of premature rupture of membranes (PROM) is essential
      to the management of pregnancy. Various tests, all with different limitations,
      have been used to diagnose PROM. Insulin-like growth factor binding protein-1
      (IGFBP-1) is present in an essentially higher concentration in amniotic fluid,
      than in serum, cervical mucous, urine and seminal plasma. A commercial kit, with
      monoclonal antibodies to IGFBP-1 attached to a stick, is available. The aim of
      this study was to investigate whether a rapid dipstick test could confirm or
      exclude the presence of amniotic fluid. METHODS: A multicenter study, involving
      six departments of obstetrics and gynecology in Sweden, was designed to evaluate
      the new dipstick technique of diagnosing the presence of amniotic fluid in the
      vagina. One hundred and seventy-four women were examined. Forty-six women with
      obvious PROM, 29 women without PROM and 99 women with suspected PROM. RESULTS:
      Forty-four out of forty-six women with obvious PROM had a positive PROM-TEST.
      Twenty-seven out of twenty-nine women without PROM had a negative PROM-TEST,
      giving a sensitivity of 95.7% and a specificity of 93.1%. Among the women with
      suspected rupture of membranes, the sensitivity was 70.8%, the specificity 88.2%
      and the positive predictive value (PPV) 92%. CONCLUSION: IGFBP is present in high
      concentration in amniotic fluid. The dipstick test with monoclonal antibodies to
      IGFBP-1 is rapid and has a high PPV, sensitivity and specificity. It is a useful
      complement to the existing arsenal of tests to detect PROM.

PMID- 9539277
TI  - Correlation of fetal oxygen saturation to fetal heart rate patterns. Evaluation
      of fetal pulse oximetry with two different oxisensors.
AB  - BACKGROUND: The purpose of this study was the correlation of fetal oxygen
      saturation values to various fetal heart rate patterns, as well as to oxygen
      saturation values obtained by fetal blood analysis. These objectives need to be
      evaluated from the perspective that two generations of fetal oxisensors have been
      used. METHODS: Two different oxisensor systems (FS10: 660+890 nm and FS14:
      735+890 nm) and a blinded pulse oximeter (type N400, Nellcor Puritan Bennett)
      were utilized to monitor 112 fetuses. All data, including oxygen saturation,
      fetal heart rate patterns, signal and contact quality were stored on a personal
      computer and evaluated after delivery. RESULTS: The following median fetal oxygen
      saturation values were obtained: during reassuring fetal heart rate sequences 54%
      with the oxisensor FS10 and 48% with the newer FS14 oxisensor, during intervals
      of variable decelerations 43% with the FS10 oxisensor and 40% with the FS14
      oxisensor. These differences between values obtained during normal and abnormal
      fetal heart rate patterns are significant. Due to non-reassuring fetal heart rate
      patterns 81 fetal blood analyses were performed. The values of pulse oximetry
      were 9% higher (6% for the FS14) than those of spectrophotometry. Correlation of
      both methods was r=0.66 (0.74 for the FS14). CONCLUSIONS: In combination with
      fetal heart rate monitoring, fetal pulse oximetry promises a better
      differentiation between low and high risk heart rate patterns. Oxygen saturation
      values from intermittent fetal blood sampling reassure the clinician concerning
      the accuracy of this new method of intrapartum fetal surveillance and underline
      the increased quality of the new generation of oxisensor using light of a
      wavelength of 735 and 890 nm.

PMID- 9539276
TI  - Vitamin D deficiency in pregnancy is not associated with obstructed labor. A
      study among Pakistani women in Karachi.
AB  - BACKGROUND: Vitamin D deficiency is widespread among pregnant Pakistanis in
      Norway. It may cause osteomalacia with destruction of maternal pelvis, and thus
      be a risk factor for cephalopelvic disproportion. This study was performed to
      determine whether vitamin D deficiency is common among pregnant Pakistanis in
      Pakistan, and to test the hypothesis that vitamin D deficiency in nulliparous
      pregnant women is associated with mechanical dystocia. METHODS: The study was
      carried out at the Civil Hospital, in a poor area of Karachi, and had a case
      referent design. Thirty-seven nulliparous parturients with Cesarean section due
      to mechanical dystocia served as cases, and 80 nulliparous parturients with
      uncomplicated vaginal delivery were their referents. All blood samples were drawn
      before parturition. RESULTS: The mothers with obstructed labor were shorter (on
      average 150 vs. 155 cm, p= 0.0001) and lighter (on average 58 vs. 60.5 kg,
      p=0.005) than their referents. Seventy-one percent (83/117) of all the
      participants had marginal or low vitamin D status defined as serum level of
      calcidiol (25-OH vitamin D3) below 30 nmol/l. Vitamin D deficiency was, however,
      not more widespread among the mothers with obstructed labor (20/37 vs. 63/80).
      Furthermore, there were no significant differences in the serum levels of the
      carboxyterminal telopeptide of type I collagen, a sensitive biochemical marker of
      bone resorption, (7.2 vs. 6.6 microg/l), and bone specific alkaline phosphate
      (18.1 vs. 22.0 U/l) a sensitive marker of bone formation. CONCLUSIONS: Vitamin D
      deficiency in pregnancy is common in Karachi, but is not associated with
      mechanical dystocia.

PMID- 9539278
TI  - Umbilical cord encirclements and Apgar scores.
AB  - OBJECTIVE: To establish the relative influence of umbilical cord encirclements
      versus fetal growth restriction in determining fetal outcome. METHODS: Twelve
      thousand and thirty-nine singleton births were studied. The number of cord
      encirclements were noted. Fetal growth restriction was measured as standard
      deviations from gestational weight. Fetal outcome was determined by using Apgar
      scores after 5 minutes. RESULTS: For growth restricted babies, Apgar 5 was not
      affected by the presence of encirclements when corrected for the level of FGR.
      Only for infants larger-for-date did the encirclements affect their Apgar score.
      CONCLUSION: The poorer outcome for babies with cord encirclements and fetal
      growth restriction is due to the accompanying level of growth restriction.

PMID- 9539280
TI  - Focusing on the pregnancy test.
AB  - BACKGROUND: Due to high abortion rates in a low status area in Goteborg, Sweden,
      a study was performed focused on the pregnancy test. METHOD AND MATERIAL: The aim
      of the study was to facilitate the accessibility of contraceptive counseling
      offering immediate and extended family planning advice to women with negative
      pregnancy tests not wishing to become pregnant. There was also an ambition to
      better understand the lack or inconsistent use of contraceptives and decrease the
      rate of unwanted pregnancies, which could have an impact on the abortion rates.
      RESULTS: In an area with 5,200 women of fertile age immediate and extended family
      planning advice was offered by midwives to all women with no desire for pregnancy
      and negative pregnancy test results. During the six month data collection period
      in 1988-1989, 463 women received such a consultation, of whom 310 did not use any
      contraceptives at the time of the study. Several reasons, on different
      explanatory levels, for not using contraception were recognized. CONCLUSION: The
      abortion rate declined in the area, and this decline was observed two years
      earlier than for the rest of Goteborg. This decline, together with the
      information on contraception behavior received, may indicate that this kind of
      approach could be successful.

PMID- 9539279
TI  - Attitudes of different groups of women in Sweden to oocyte donation and oocyte
      research.
AB  - OBJECTIVES: To evaluate attitudes of Swedish women towards oocyte donation and
      oocyte research. METHODS: Five different groups of women, with approximately 50
      patients in each, were asked anonymously about their attitudes to legislation,
      tentative roles as donors or recipients, anonymity, suitable donors or
      recipients, research on fetuses and cadavers as a source of oocytes, age limits
      and economic aspects. The groups were: 1. Women undergoing IVF treatment (IVF).
      2. Infertile women during work-up (INF). 3. Recently delivered women attending a
      maternity unit (MAT). 4. Women attending a family planning center applying for
      therapeutic abortion (FPC). 5. Women with Turner's syndrome (TUR). RESULTS: More
      than 90% of women in all groups investigated advocated amendment of the law in
      order to permit oocyte donation. The women of infertile groups were more in favor
      of donating oocytes compared to women of fertile groups (p<0.05). A great
      majority would prefer anonymity both if they were donors and if they were
      recipients. If no anonymity was guaranteed, the acceptance of both the donor and
      recipient groups decreased but more than half of the women in all groups would
      still donate/accept oocytes. There was a significant difference in attitude
      towards non-anonymous oocyte donation, with the highest acceptance among Turner
      patients and the lowest among IVF patients (p<0.01). A majority in all groups
      were more motivated to donate/accept oocytes from a close relative, with the
      exception of Turner patients (p<0.01). All groups had a negative attitude to the
      use of donated fetuses and cadavers as sources of oocytes. IVF patients, close
      relatives and volunteers were all regarded as suitable donors by a majority of
      women in all groups. Women of fertile age, with ovarian failure or a genetic
      disorder, were accepted as recipients by all groups. Postmenopausal women were
      not accepted as recipients by a great majority in all groups. All groups
      preferred an age limit for recipients. More than 70% set the limit to the
      interval 40 to 45 years of age. A majority in all groups believed that donors
      should be paid to cover medication and loss of income. The recipients were
      expected, by a majority of women, to pay for some of the costs of the oocyte
      donation program. CONCLUSIONS: A great majority wanted a change in the Swedish
      legislation to permit oocyte donation. All groups had a generous attitude to
      donation of oocytes although anonymity would be preferred. Ovarian dysfunction
      and genetic disorders among women of fertile age were regarded as major
      indications for oocyte donation. IVF patients, close relatives and volunteers
      were all regarded as acceptable donors.

PMID- 9539281
TI  - Prolonged vaginal bleeding during central precocious puberty therapy with a long
      acting gonadotropin-releasing hormone agonist.
AB  - OBJECTIVE: To describe our experiment with the treatment of GnRH-a in
      premenarchal girls with idiopathic central precocious puberty (CPP). PATIENTS AND
      METHODS: Twenty-eight girls, aged 6.5-11 years, with idiopathic central
      precocious puberty were treated every 28 days with an intramuscular depot
      gonadotropin releasing hormone agonist (GnRH-a) in an attempt to delay sexual
      maturation. RESULTS: Eight of the 28 (28.5%) developed vaginal bleeding after
      GnRH-a administration. Of these, prolonged vaginal bleeding of 11-13 days
      occurred in four girls, three recurrent episodes occurred in one during the
      second injection, and in one other girl the 4th episode occurred after 6 months
      of treatment. CONCLUSION: Uterine bleeding following GnRH-a treatment in
      premenarchal girls with CPP is common, and may be massive and recurrent, since
      most episodes resolved spontaneously and necessitated no further treatment,
      careful advice should be given to the girls and their families prior to treatment
      initiation, in an attempt to avoid unnecessary anxiety and achieve better
      compliance.

PMID- 9539282
TI  - Effect of estrogen-progestin hormonal replacement therapy on plasma antithrombin
      III of postmenopausal women.
AB  - BACKGROUND: This study was performed to evaluate antithrombin III levels in
      postmenopausal women receiving hormonal replacement treatment. METHODS: It is a
      prospective randomized study concerning 19 postmenopausal patients, aged 40 to 65
      years, who received either continuous daily oral equine conjugated estrogen 0.625
      mg (group A, N=10) or daily transdermal 17beta-estradiol 50 microg (group B,
      N=9). Medroxyprogesterone acetate (5 mg/day, 14 days monthly) was given to all
      patients. Blood samples were obtained before and after 3, 6, 9 and 12 months of
      treatment. Coagulation tests included Antithrombin III (functional method),
      prothrombin time, partial activated prothrombin time, thrombin time, factor V,
      fibrinogen, platelet count and euglobulin lysis time. Friedman analysis of
      variance and Mann-Whitney test were used for statistical analysis. RESULTS:
      Antithrombin III level was reduced (p<0.05) in group A but not in group B,
      although it remained within normal range. No changes were detected in the other
      coagulation tests. CONCLUSIONS: These data suggest that oral conjugated estrogen
      replacement reduces functional ATIII, whereas transdermal estradiol replacement
      therapy does not modify it.

PMID- 9539283
TI  - Transarterial embolization of the uterine arteries: patient reactions and effects
      on uterine vasculature.
AB  - BACKGROUND: Therapeutic embolization of the uterine arteries has been
      successfully used to manage profuse gynecological hemorrhage. In the present
      study we aimed to investigate whether embolization of uterine arteries may serve
      as a safe and effective alternative treatment in cases of menorrhagia in fertile
      and perimenopausal women. As a first step, we have evaluated the methodology,
      patient reactions and effects on the uterine vasculature. METHODS: The distal
      part of the uterine artery was embolized with polyvinyl alcohol particles via
      catheterization of the right femoral artery. Total abdominal hysterectomy was
      performed the next day. RESULTS: Bilateral embolization in two patients resulted
      in considerable pain that required morphine analgesic medication and epidural
      analgesia. One patient was embolized unilaterally and experienced only slight
      discomfort with no need for analgesic medication at all, indicating that
      unilateral embolization is a well-tolerated method. After embolization,
      angiography showed stagnant flow in embolized vessels without contrast filling of
      distal branches. Angiography of the specimen showed normal vascular architecture
      in non-treated vessels. In treated vessels the main arterial trunks were patent
      but all smaller branches were occluded. Histology showed that most of the
      particles lodged in small arteries and that arterioles never showed injected
      material. CONCLUSION: The study indicates that the procedure involves an
      efficient occlusion of uterine vessels and that unilateral embolization of
      uterine arteries is well tolerated.

PMID- 9539284
TI  - Results of the anti-incontinence operations and Kegel exercises in patients with
      type II anatomic stress incontinence.
AB  - BACKGROUND: To evaluate the results of anti-incontinence operations and Kegel
      exercises in patients with pure type II anatomic stress incontinence. METHODS:
      After evaluation by physical, genitourinary and urologically oriented
      neurological examinations, urogynecologic tests, perineal ultrasonography and
      cystometry, pure type II anatomic stress incontinence was diagnosed in 98
      patients. Modified Pereyra and Burch operations were performed in 27 and 24 of
      the 51 (52.0%) patients, who had surgical treatments, respectively, while the
      remaining 47 (48.0%) patients were advised to perform Kegel exercise. The results
      of the treatment methods were evaluated subjectively by patient questionnaire and
      24-hour urinary diary and objectively by one-hour pad test and stress test.
      RESULTS: Fifty-one patients treated by anti-incontinence operations had 90.2%
      objective and 94.1% subjective complete successes (cure) with a mean follow-up of
      13.7 months. These data were 8.5% and 14.9% respectively, for 47 patients treated
      by Kegel exercises with a mean follow-up of 12.8 months. Both the subjective and
      objective cure rates of surgical treatments were found to be significantly higher
      than those of Kegel exercises in patients with type II anatomic stress
      incontinence (p<0.01). Patients with good compliance to Kegel exercises had 20.7%
      subjective and 13.8% objective cures, however those with low compliance had only
      5.6% subjective and no objective cures. CONCLUSIONS: These data suggested that
      anti-incontinence operations were more effective than Kegel exercises for the
      treatment of patients with type II anatomic stress incontinence.

PMID- 9539285
TI  - The role of routine pelvic lymph node sampling in patients with stage I
      endometrial carcinoma: second thoughts.
AB  - BACKGROUND AND METHODS: The cases of 245 patients diagnosed during 1980-1989 with
      stage I endometrial carcinoma were retrospectively reviewed in order to assess
      the contribution of lymph node sampling (LNS) to both course of treatment and
      outcome. The 183 women treated by gyneco-oncologic surgeons had undergone the
      standard surgical procedure of total abdominal hysterectomy (TAH), bilateral
      salpingo-oophorectomy (BSO) and pelvic lymph node sampling (LNS). Sixty-two other
      women, treated by gynecologists, received only TAH and BSO. Of women who had
      received TAH+BSO+LNS, 105 (57.4%) were referred for adjuvant radiotherapy on the
      basis of one or any combination of high grade histology (G2 or G3), myometrial
      invasion to a depth of 50% or more and LNS positivity. Of the group who had not
      had LNS, 37 (59.7%) likewise received adjuvant radiotherapy but on the bases of
      histology and/or depth of invasion. RESULTS AND CONCLUSIONS: Recurrence and
      survival over a mean follow-up period of 7.5 years (range 5-15 years) showed no
      significant differences between the patients who underwent LNS and those who did
      not. Of 43 recurrences, six were among 'low risk' women (those with both minimal
      invasion and low grade histology), suggesting a special need among this group for
      the additional staging information which LNS may provide.

PMID- 9539286
TI  - Predisposing psychological factors for posttraumatic stress reactions after
      emergency cesarean section.

PMID- 9539287
TI  - Flecainide against fetal supraventricular tachycardia complicated by hydrops
      fetalis.

PMID- 9539289
TI  - A rare case of vulval and perineal leiomyoma.

PMID- 9539288
TI  - Postpartum thrombosis after a successful pregnancy in a recurrent aborter
      strongly positive for antiphospholipid antibodies.

PMID- 9539290
TI  - Primary retroperitoneal mucinous cystadenoma.

PMID- 9539291
TI  - Aggressive radiotherapy for stage IIIB cancer of the cervix: helpful or harmful?

PMID- 9539292
TI  - Genetic, metabolic and clinical characteristics of maturity onset diabetes of the
      young.
AB  - Maturity onset diabetes of the young (MODY) is a genetically and clinically
      heterogeneous subtype of non-insulin-dependent diabetes mellitus (NIDDM)
      characterised by early onset, autosomal dominant inheritance and a primary defect
      in insulin secretion. To date, three MODY genes have been identified on
      chromosomes 20q (MODY1/hepatic nuclear factor (HNF)-4alpha), 7p
      (MODY2/glucokinase) and 12q (MODY3/HNF-1alpha). Mutations in MODY2/glucokinase
      result in mild chronic hyperglycaemia as a result of reduced pancreatic beta-cell
      responsiveness to glucose, and decreased net accumulation of hepatic glycogen and
      increased hepatic gluconeogenesis after meals. In contrast, MODY1 and MODY3 are
      characterised by severe insulin secretory defects, and by major hyperglycaemia
      associated with microvascular complications. The role of the three known MODY
      genes in susceptibility to the more common late-onset NIDDM remain uncertain.
      Genetic studies seem to exclude a role as major susceptibility genes, but leave
      unresolved whether they may have a minor role in a polygenic context or an
      important role in particular populations.

PMID- 9539293
TI  - Autoregulation of hepatic glucose production.
AB  - In vitro evidence indicates that the liver responds directly to changes in
      circulating glucose concentrations with reciprocal changes in glucose production
      and that this autoregulation plays a role in maintenance of normoglycemia. Under
      in vivo conditions it is difficult to separate the effects of glucose on neural
      regulation mediated by the central nervous system from its direct effect on the
      liver. Nevertheless, it is clear that nonhormonal mechanisms can cause
      significant changes in net hepatic glucose balance. In response to hyperglycemia,
      net hepatic glucose output can be decreased by as much as 60-90% by nonhormonal
      mechanisms. Under conditions in which hepatic glycogen stores are high (i.e. the
      overnight-fasted state), a decrease in the glycogenolytic rate and an increase in
      the rate of glucose cycling within the liver appear to be the explanation for the
      decrease in hepatic glucose output seen in response to hyperglycemia. During more
      prolonged fasting, when glycogen levels are reduced, a decrease in
      gluconeogenesis may occur as a part of the nonhormonal response to hyperglycemia.
      A substantial role for hepatic autoregulation in the response to insulin-induced
      hypoglycemia is most clearly evident in severe hypoglycemia (< or = 2.8 mmol/l).
      The nonhormonal response to hypoglycemia apparently involves enhancement of both
      gluconeogenesis and glycogenolysis and is capable of supplying enough glucose to
      meet at least half of the requirement of the brain. The nonhormonal response can
      include neural signaling, as well as autoregulation. However, even in the absence
      of the ability to secrete counterregulatory hormones (glucocorticoids,
      catecholamines, and glucagon), dogs with denervated livers (to interrupt neural
      pathways between the liver and brain) were able to respond to hypoglycemia with
      increases in net hepatic glucose output. Thus, even though the endocrine system
      provides the primary response to changes in glycemia, autoregulation plays an
      important adjunctive role.

PMID- 9539294
TI  - Serum thyroglobulin determination in the follow-up of patients with
      differentiated thyroid carcinoma.

PMID- 9539295
TI  - Insulin sensitizing agents and polycystic ovary syndrome.

PMID- 9539296
TI  - Growth factors and human pituitary adenomas.

PMID- 9539297
TI  - Growth hormone and idiopathic short stature--it is too soon to call it a mis
      trial.

PMID- 9539298
TI  - Insulin resistance and the regulation of vascular tone: is insulin a vasodilator?

PMID- 9539299
TI  - Stronger bonds between 25-hydroxyvitamin D 1alpha-hydroxylase and pseudovitamin D
      deficiency rickets.

PMID- 9539300
TI  - Therapeutic effects of metformin on insulin resistance and hyperandrogenism in
      polycystic ovary syndrome.
AB  - Evidence suggests that insulin resistance and hyperinsulinaemia are associated
      with ovarian hyperandrogenism and menstrual irregularities in polycystic ovary
      syndrome (PCOS). Sixteen obese women with PCOS on a weight-maintaining diet were
      studied before and after 6 months of therapy with the insulin-sensitizing
      antidiabetic agent metformin at a dose of 1700 mg per day. Compared with baseline
      values, glucose utilization was markedly enhanced at 6 months using the two-step
      euglycaemic-hyperinsulinaemic clamp to measure changes in insulin sensitivity
      (2.56 +/- 0.32 vs 4.68 +/- 0.49 mg/kg per min, P = 0.0001, when 40 mU insulin/m2
      per min was infused, and 6.48 +/- 0.58 vs 9.84 +/- 0.72 mg/kg per min, P =
      0.0002, when 400 mU insulin insulin/m2 per min was infused). The improvement in
      insulin action was accompanied by significant increases in the levels of sex
      hormone-binding globulin (24.5 +/- 7.2 vs 39.8 +/- 16.2 nmol/l, P = 0.003) and
      decreases in free testosterone (12.8 +/- 5.8 vs 9.0 +/- 3.0 pmol/l, P = 0.03) and
      androstenedione (12.9 +/- 5.6 vs 7.3 +/- 1.7 nmol/l, P = 0.003). No significant
      changes were recorded in body weight. Seven subjects resumed normal menstruation
      and two cases of spontaneous pregnancy occurred during treatment. Metformin was
      well tolerated except for one case of flatulence. These results confirm that
      metformin treatment can lead to improvements in insulin resistance and ovarian
      hyperandrogenism.

PMID- 9539301
TI  - Effect of growth hormone therapy in children with achondroplasia: growth pattern,
      hypothalamic-pituitary function, and genotype.
AB  - OBJECTIVE: Although there are a few reports on GH therapy in achondroplasia,
      these were based on a small sample and/or short-term observation. To clarify the
      effectiveness of GH treatment on short stature in achondroplasia and
      hypochondroplasia, a long-term treatment study in a larger number of patients was
      performed. METHOD: Forty-two children (16 males and 26 females, age 3-14 years)
      with achondroplasia were examined in this study. Initially, we evaluated
      hypothalamic-pituitary function and point mutation analysis as previously
      reported. After the evaluation, the children were treated with GH for more than 2
      years; then post-treatment growth velocity and body proportion parameters were
      determined. RESULTS: The 35 typical variants of our achondroplasia patients
      showed previously reported point mutation in the fibroblast growth factor
      receptor 3 gene. The annual height gain during GH therapy was significantly
      greater than that before therapy (3.9 +/- 1.0 cm/year before treatment vs 6.5 +/-
      1.8 cm/year for the first year and 4.6 +/- 1.6 cm/year for the second year of
      treatment). The body disproportion had not been aggravated during the treatment
      period. CONCLUSION: We conclude that GH might be beneficial in the treatment of
      short stature in children with achondroplasia in the first 2 years of treatment.

PMID- 9539302
TI  - Preserved activation of thyrotropin receptor antibody to stimulate thyroid
      function despite long-term treatment in euthyroid patients with Graves' disease.
AB  - Clinical evaluation was conducted to ascertain whether thyrotropin receptor
      antibody (TRAb) in the normal range may still be involved in the regulation of
      thyroid function after prolonged treatment for Graves' disease. All patients (n =
      33) were treated with antithyroid drugs for an average of 10.6 years and were
      under euthyroid conditions in which normal blood levels of tri-iodothyronine (T3)
      were significantly correlated with blood thyrotropin (TSH) levels, but not with
      titers of TRAb. A significant correlation was observed between TRAb titer and
      thyroid-stimulating antibody (TSAb) activity. In contrast, this correlation was
      not found in normal subjects. After administration of T3 (75 microg daily for 8
      days), the patients showed increased levels of T3 with concomitant suppression of
      TSH levels. Under these conditions, linear regression analysis showed significant
      correlations of TRAb titer and TSAb activity with 24-h thyroid radioiodine uptake
      (r = 0.641 and 0.621 respectively, P < 0.01), in contrast to declining blood
      thyroxine levels. Moreover, the immunoglobulin G (IgG) of the patients
      precipitated to a greater extent than IgG from normal subjects a peptide
      consisting of the amino acid sequence near the terminus of the human TSH
      receptor. These findings indicated that TRAb at normal levels possessed
      significant unremitting activities on thyroid function despite long-term
      treatment in euthyroid patients with Graves' disease.

PMID- 9539303
TI  - Cabergoline treatment rapidly improves gonadal function in hyperprolactinemic
      males: a comparison with bromocriptine.
AB  - This study evaluated the effects of chronic treatment with cabergoline (CAB), a
      new, potent and long-lasting ergoline-derived dopamine agonist, on seminal fluid
      parameters and sexual and gonadal function in hyperprolactinemic males in
      comparison with the effect of bromocriptine (BRC) treatment. Seventeen males with
      macroprolactinoma were treated with CAB at a dose of 0.5-1.5 mg/week (n = 7), or
      BRC at a dose of 5-15 mg/day (n = 10) for 6 months. Baseline prolactin (PRL) was
      925.7 +/- 522.6 microg/l in the CAB-treated group and 1059.4 +/- 297.6 microg/l
      in the BRC-treated group. All the patients suffered from libido impairment, ten
      from reduced sexual potency, and six had infertility. In five patients
      provocative bilateral galactorrhea was found. Seminal fluid analysis, functional
      seminal tests and penis rigidity and tumescence, measured by nocturnal penile
      tumescence (NPT) using Rigiscan equipment, were assessed before and after 1, 3
      and 6 months of CAB or BRC treatment. Hormone profiles were assessed before and
      after 15, 30, 60, 90 and 180 days of both treatments. Before treatment, all
      patients had a low sperm count with oligoasthenospermia, reduced motility and
      rapid progression with an abnormal morphology and decreased viability, and a low
      number of erections. After 1 month, serum PRL levels were significantly reduced
      in both groups of patients (20.6 +/- 6.6 microg/l during CAB and 256.3 +/- 115.1
      microg/l during BRC treatment) and were normalized after 6 months in all patients
      (CAB: 7.9 +/- 2.2 microg/l; BRC: 16.7 +/- 1.8 microg/l). After 6 months, a
      significant increase of number, total motility, rapid progression and normal
      morphology was recorded in patients treated with both CAB and BRC. An increase in
      the number of erections during the first 3 months of both treatments was noted by
      NPT. However, the improvements in seminal fluid parameters and sexual function
      were more evident and rapid in patients treated with CAB. The number of erections
      was normalized after 6 months of treatment in all patients submitted to CAB
      treatment, and in all patients but one treated by BRC. In addition, a significant
      increase of serum testosterone (from 3.7 +/- 0.3 to 5.3 +/- 0.2 microg/l) and
      dihydrotestosterone (from 0.4 +/- 0.1 to 1.1 +/- 0.1 nmol/l) was recorded. At the
      beginning of treatment, mild side-effects were recorded in two patients after CAB
      and mild-to-moderate side-effects in five patients after BRC administration. The
      treatment with CAB normalized PRL levels, improving gonadal and sexual function
      and fertility in males with prolactinoma, earlier than did BRC treatment,
      providing good tolerability and excellent patient compliance to medical
      treatment.

PMID- 9539304
TI  - Desmopressin and low-dose ACTH test in rheumatoid arthritis.
AB  - OBJECTIVE: To ascertain whether a different regulation and sensitivity of the
      hypothalamic-pituitary-adrenal axis exists and whether a type of cortisol
      resistance is present in rheumatoid arthritis (RA) patients, a chronic disease in
      whose pathogenesis modifications of the steroid milieu are involved. DESIGN: We
      studied the basal and dynamic response of ACTH and adrenal steroids to various
      stimuli acting on the hypophysis or directly on the adrenal gland. METHODS: We
      studied ten RA patients (39.8 +/- 7.4 (S.D.) years), defined according to the
      American Rheumatism Association, and seven healthy control patients (34.1 +/- 9.6
      (S.D.) years). All subjects underwent testing, in random order, with placebo,
      desmopressin (DDAVP) (10 microg i.v.), ovine corticotropin-releasing hormone
      (oCRH) (1 microg/kg body weight) and low-dose ACTH (5 microg i.v.), during the
      follicular phase of two different menstrual cycles. Blood samples were collected
      at different times for ACTH and adrenal steroids assay. Baseline estradiol (E2),
      testosterone and IGF-I levels were also evaluated. All subjects collected urine
      specimens for 24 h urine free cortisol (UFC). RESULTS: No difference in E2,
      testosterone or UFC was found between RA patients and controls. IGF-I levels were
      significantly (P < 0.01) lower in RA patients (110.6 +/- 6.4 microg/l) than in
      controls (207.0 +/- 37.9 microg/l). Mean baseline dehydroepiandrosterone (DHEA)
      and delta4-androstenedione levels of the four tests were significantly (P < 0.05)
      lower in RA patients than in controls. In RA, a negative correlation was found
      between mean DHEA levels, class of disease (r = -0.67, P < 0.05) and erythrocyte
      sedimentation rate (r = -0.63, P < 0.05). After placebo no difference in ACTH and
      cortisol area under curves (AUCs) was found between RA patients and controls.
      After DDAVP no cortisol or ACTH response was found in RA patients, while a
      significant (P < 0.05) ACTH release was found in controls. Only in RA patients
      was DDAVP able to induce a significant (P < 0.01) DHEA increase. After oCRH a
      similar significant response in ACTH (P < 0.05), cortisol (P < 0.01), and DHEA (P
      < 0.01) was found in both groups. After low-dose ACTH, a similar significant (P <
      0.01) cortisol response was found in both RA patients and controls; indeed in RA
      patients DHEA AUC (2196.0 +/- 321.8 nmol/l per 90 min) was significantly lower (P
      < 0.01) than DHEA AUC (4280.8 +/- 749.0 nmol/l per 90 min) in controls. A similar
      significant (P < 0.01), though not abnormal, 17-hydroxyprogesterone response to
      ACTH was found in both groups. CONCLUSIONS: Our study underlines reduced adrenal
      steroid and IGF-I levels, but not the previously described cortisol resistance in
      RA patients; it shows that baseline and dynamic cortisol levels are 'normal' but
      inadequate in the setting of a sustained inflammatory disease like RA. The
      reduced basal and low-dose ACTH-induced DHEA levels could reflect both a reduced
      sensitivity of the adrenal gland to exogenous corticotropin and a decreased
      steroid synthesis due to a partial adrenal enzymatic defect (P450 17,20 lyase).

PMID- 9539305
TI  - Stimulation of erythropoietin secretion by continuous subcutaneous infusion of
      recombinant human GH in anemic patients with chronic renal failure.
AB  - We have investigated the effect of human GH on erythropoietin (EPO) secretion in
      eight anemic patients with chronic renal failure (CRF) (three males and five
      females, aged from 46 to 83 years). Recombinant human GH was infused
      subcutaneously at a flow rate of 2 microg/kg body weight per 0.1 ml/h for 72 h
      using a portable infusion pump. Blood samples were obtained immediately before
      and 2, 4, 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120 and 168 h after the start
      of GH infusion. Storage urine samples were obtained before and 24, 48 and 72 h
      after the start of the infusion. The mean (+/- S.E.M.) basal plasma GH levels
      increased from 1.9 +/- 0.3 to 18.8 +/- 0.7 microg/l during the GH infusion.
      Plasma IGF-I levels increased 12 h after the start of GH treatment and the mean
      peak values of 403.6 +/- 38.5 microg/l were obtained at 72 h. Plasma EPO levels
      increased 6 h after the start of GH infusion, and the peak values of 38.4 +/-
      11.6 IU/l were obtained at 96 h (P < 0.05 vs basal values 24.5 +/- 7.2 IU/l).
      Reticulocyte counts increased from 28.7 +/- 5.2 x 10(3)/microl to 40.3 +/- 8.0 x
      10(3)/l at 108 h, 43.6 +/- 9.2 x 10(3)/microl at 120 h and 41.7 +/- 7.7 x
      10(3)/microl at 160 h (P < 0.05). Serum urea nitrogen decreased at 72 h (P <
      0.05), whereas there was no significant change in urinary excretion of nitrogen.
      Hemoglobin levels were not significantly changed throughout the experimental
      period. These findings indicate that human GH has a stimulating effect on EPO
      secretion in anemic patients with CRF.

PMID- 9539306
TI  - Effects of corticotrophin-releasing hormone, vasopressin and insulin-like growth
      factor-I on proliferation of and adrenocorticotrophic hormone secretion by canine
      corticotrophic adenoma cells in vitro.
AB  - Extrinsic factors such as hypothalamic hormones or intrapituitary growth factors
      may stimulate clonal expansion of a genomically altered cell and therefore play a
      role in pituitary tumorigenesis. Here we report on the effects of the
      hypophysiotrophic hormones corticotrophin-releasing hormone (CRH) and vasopressin
      (AVP) and the intrapituitary growth factor insulin-like growth factor-I (IGF-I)
      on the proliferation of, as measured by the bromodeoxyuridine labelling index,
      and ACTH secretion by normal canine pituitary cells and corticotrophic adenoma
      cells of dogs with pituitary-dependent hyperadrenocorticism. The sensitivity to
      inhibition by cortisol was analysed under various conditions. Under basal
      conditions, no significant differences were found in the bromodeoxyuridine
      labelling indices between control cells and tumour cells. CRH, AVP, IGF-I and
      cortisol had no effect on the proliferation of canine pituitary cells or canine
      corticotrophic adenoma cells. In contrast with normal pituitary cells, the
      proliferation of corticotrophic adenoma cells was stimulated by fetal calf serum
      (FCS). This FCS-induced proliferation was not inhibited by cortisol. The CRH
      induced ACTH secretion by corticotrophic adenoma cells was significantly (P <
      0.05) lower than that by normal pituitary cells after 4 h incubation with CRH.
      Incubation with cortisol for 24 h resulted in reduced ACTH secretion under basal
      and AVP- or IGF-I-stimulated conditions. The relative inhibition was, however,
      significantly (P < 0.05) lower in ACTH-producing tumour cells than in normal
      pituitary cells. Cortisol did not inhibit the CRH-induced ACTH secretion in
      normal pituitary cells after 24 h. In conclusion, canine corticotrophic adenomas
      are less sensitive to stimulation by CRH and less sensitive to inhibition by
      glucocorticoids. These tumours have an aberrant sensitivity to a growth-promoting
      factor present in FCS. This factor may have an important role in the growth
      promotion of canine corticotrophic tumours.

PMID- 9539308
TI  - Changes in carbohydrate metabolism of testicular germ cells during meiosis in the
      rat.
AB  - A study was undertaken to estimate the activities of the key enzymes of
      glycolysis, the pentose phosphate pathway and the tricarboxylic acid (TCA) cycle
      in purified rat spermatocytes and spermatids, which have been shown to die in
      glucose-containing medium and require lactate/pyruvate for maintaining normal ATP
      concentrations. The aim was to elucidate the changes in the glycolytic and
      oxidative potential of germ cells undergoing meiosis. Pachytene spermatocytes and
      round spermatids from adult rat testis were purified to approximately 90% purity
      by trypsin digestion followed by a combination of centrifugal elutriation and
      Percoll density gradient centrifugation. After the purity and viability of these
      cells had been established, their contents of hexokinase, phosphofructokinase,
      lactate dehydrogenase (LDH) and LDH-X of glycolysis, glucose 6-phosphate
      dehydrogenase of the pentose phosphate pathway and citrate synthase, aconitase,
      malate dehydrogenase and 2-oxoglutarate dehydrogenase of the TCA cycle were
      estimated. These enzymes were also estimated in epididymal spermatozoa for
      comparison with the testicular germ cells. The results indicate greater activity
      of glycolytic and pentose phosphate pathway enzymes in spermatocytes than in
      spermatids, which exhibited greater activity of TCA cycle enzymes than the
      former. The difference in activity was statistically significant for most of the
      enzymes studied. In contrast, spermatozoa exhibited markedly greater activity of
      glycolytic enzymes and significantly lower activity of pentose phosphate pathway
      and TCA cycle enzymes than did the testicular germ cells. We conclude that the
      unusual dependence of spermatids exclusively on lactate may be due to their lower
      glycolytic potential, whereas spermatocytes with comparatively greater glycolytic
      activity have an intermediate dependence on lactate and are therefore able to
      utilise lactate, pyruvate, or both, while retaining a better ability to utilise
      glucose. Spermatozoa with the greatest glycolytic potential and the lowest TCA
      cycle activity appear to be 'programmed' to utilise exclusively glucose/fructose
      for energy.

PMID- 9539307
TI  - Aging is associated with changes in allopregnanolone concentrations in brain,
      endocrine glands and serum in male rats.
AB  - OBJECTIVE: Allopregnanolone is a potent neuroactive steroid hormone produced in
      the brain and in peripheral endocrine glands. The present study investigated
      possible age-related variations in allopregnanolone content in brain areas,
      endocrine glands and serum of male rats. DESIGN: Wistar male rats were
      categorized into 5 groups (6 rats in each) according to age: 6, 12, 16, 18 and 20
      months respectively. METHODS: Allopregnanolone content in acidic homogenates of
      brain cortex, hypothalamus, pituitary, adrenals and gonads was measured by a
      specific radioimmunoassay. Serum allopregnanolone, corticosterone and
      testosterone were also assayed by radioimmunoassay. RESULTS: Brain cortex
      allopregnanolone content decreased significantly with age, while hypothalamic
      allopregnanolone content remained constant until 18 months and increased
      significantly at 20 months. Pituitary content showed a significant age-related
      reduction. Adrenal allopregnanolone content remained constant until 18 months,
      and was significantly higher at 20 months. Testis and serum allopregnanolone
      contents showed significant age-related increases. Serum testosterone levels
      showed an age-related decrease, while no age-related variation in serum
      corticosterone was found. CONCLUSIONS: The present study showed a significant
      impact of aging on allopregnanolone contents in brain, endocrine glands and
      serum, showing an age-related decrease in brain cortex and pituitary, and an age
      related increase in testes, adrenals and serum.

PMID- 9539309
TI  - Inhibition by gonadotropins of interleukin-1 production by rabbit granulosa and
      theca cells: effects on gonadotropin-induced progesterone production.
AB  - Increasing evidence suggests that cytokines may play a role in ovarian processes.
      The purpose of this study was to determine if interleukin-1 (IL-1) could modulate
      rabbit pre-ovulatory follicular function and to explore cellular sites of IL-1
      biosynthesis in rabbit follicles. Development of rabbit pre-ovulatory follicles
      was induced by 200 mIU equine chorionic gonadotropin daily for 2 days. Seventy
      two hours after the last injection, ovaries were excised and granulosa and theca
      cells isolated. The two types of cell were pre-incubated for 24 h in Minimum
      Essential Medium (MEM) with 5% fetal calf serum (FCS), and then incubated for 24
      h in MEM with 2.5% FCS with appropriate stimulants. Results showed that rabbit
      granulosa and theca cell culture supernatants contain IL-1 bioactivity and that
      this bioactivity was diminished by gonadotropins, FSH and human chorionic
      gonadotropin, in a dose-dependent manner. Low doses of IL-1 (1 ng/ml) inhibited
      gonadotropin-induced progesterone production in both cell types and at the same
      time increased cell numbers. A study of the mechanism of IL-1 action demonstrated
      that it affects cAMP generation, and also steps distal to cAMP formation. We
      conclude that in our model gonadotropins, by inhibiting IL-1 production, could
      control IL-1 modulation of gonadotropin action on steroidogenesis.

PMID- 9539310
TI  - Elevated insulin-like growth factor (IGF) binding protein (IGFBP)-2 and IGFBP-4
      expression of leukemic T-cells is affected by autocrine/paracrine IGF-II action
      but not by IGF type I receptor expression.
AB  - We recently found evidence indicating that the source of elevated serum insulin
      like growth factor binding protein (IGFBP)-2 in leukemia was the leukemic T
      cells. Here we report that locally produced IGF-II affects IGFBP-2 expression and
      growth of leukemic cells through the IGF type I receptor. We measured IGFBP-2, -4
      and IGF type I receptor (IGF-I-R) mRNA by RT-PCR, cell growth and IGFBP-2
      secretion (per 10(6) cells). IGF-I-R binding sites were assessed by 125I-IGF
      replacement studies. Inhibition using an IGF-II antibody showed that tumor cell
      derived IGF-II accounts for a significant 25% (P < 0.001) increase in IGFBP-2
      secretion and enhanced growth (P < 0.01) of leukemic T-cells after 7 days in
      culture. IGFBP-2 secretion, but not IGFBP-2 mRNA was specifically increased by
      IGFs, while no specific effect of insulin was detectable. The addition of 100
      ng/ml IGF-II enhanced the IGFBP-2 secretion 2.8-fold, while the use of IGF-I only
      enhanced IGFBP-2 secretion 1.7-fold, although IGF-I enhanced IGF-II action.
      Through inhibition using JB1, a peptide inhibiting the IGF signal transduction by
      blocking the IGF-I-R, we demonstrated the involvement of the IGF-I-R in IGFBP-2
      and -4 expression and leukemic cell growth. However, only slight differences in
      the IGF-I-R mRNA expression were seen for T- and B-cells compared with the
      differences found for the IGFBP-2 and -4 mRNA or IGFBP-2 secretion. Thus,
      although IGF-I-R mediates the autocrine/paracrine effects of the IGFs, IGF-I-R
      mRNA expression is most probably not involved in the differential IGFBP-2/IGFBP-4
      expression in leukemic cells.

PMID- 9539311
TI  - Bradykinin potentiates insulin-stimulated glucose uptake and enhances insulin
      signal through the bradykinin B2 receptor in dog skeletal muscle and rat L6
      myoblasts.
AB  - Previously we demonstrated that bradykinin infusion could increase glucose uptake
      into dog peripheral tissues, and that bradykinin could potentiate insulin-induced
      glucose uptake through glucose transporter 4 (GLUT4) translocation in dog
      adipocytes. However, skeletal muscle is the predominant tissue for insulin
      mediated glucose disposal. The aim of this study was to determine how bradykinin
      affected insulin-stimulated glucose uptake in dog skeletal muscle and myotubes
      transformed from rat L6 myoblasts. The bradykinin receptor binding studies
      revealed that dog skeletal muscle and rat L6 myoblasts possessed significant
      numbers of bradykinin receptors (Kd = 88 and 76 pmol/l, Bmax = 82.5 and 20
      fmol/mg protein respectively). An RT-PCR (reverse transcriptase-polymerase chain
      reaction) amplification showed mRNA specific for bradykinin B2 receptor in both
      cells. Bradykinin significantly increased 2-deoxyglucose uptake in isolated
      muscle and L6 myoblasts in the presence of insulin (10(-7) mol/l) in a dose
      dependent manner, but not in the absence of insulin. Bradykinin also enhanced
      insulin-stimulated GLUT4 translocation, and insulin-induced phosphorylation of
      insulin receptor beta subunit and insulin receptor substrate-1 (IRS-1) without
      affecting the binding affinities or numbers of cell surface insulin receptors in
      both cells. It is concluded that bradykinin could potentiate the insulin-induced
      glucose uptake through GLUT4 translocation in dog skeletal muscle and rat L6
      myoblasts. This effect could be explained by the potency of bradykinin to
      upregulate the insulin receptor tyrosine kinase activity which stimulates
      phosphorylation of IRS-1, followed by an increase in GLUT4 translocation.

PMID- 9539312
TI  - Molecular bases of coronary heart disease in Koreans.
AB  - Coronary heart disease (CHD) has been considered as a multifactorial disorder
      with the involvement of both environmental and genetic factors. The advent of
      tools to investigate individual variability of DNA has allowed us to perform the
      association studies of candidate genes. However, an association between genetic
      trait and phenotypic variations is not easy to demonstrate and several reported
      association between genetic markers and risk factors or overt CHD have gone
      unconfirmed. It should not be assumed that for a given genetic trait, the impact
      on risk will be similar in all populations. In particular, most studies of the
      molecular bases of CHD have involved Caucasian subjects, so much more work with
      the Korean population is needed before genetic testing for susceptibility to CHD
      can be offered to Koreans as a clinical service. In this review, we discuss two
      aspects of the molecular bases of CHD: i) Molecular bases of the candidate gene
      related to lipoprotein metabolism including apolipoprotein AI-CIII-AIV gene
      duster, apolipoprotein B, apolipoprotein E-CI-CII gene cluster,
      apolipoprotein(a), LDL receptors, lipoprotein lipase, cholesteryl ester transfer
      protein, and apo B editing protein; ii) Molecular bases of the candidate gene
      related to thrombotic and other factors including fibrinogen, factor VII,
      plasminogen activator inhibitor 1, homocysteine, stromelysin, paraoxonase, and
      angiotensin converting enzyme. Studies involving the Korean population,
      especially those performed by our teams, are also summarized.

PMID- 9539313
TI  - Identification of insulin-like growth factor (IGF)-I and IGF-binding protein in
      chylous ascites.
AB  - Insulin-like growth factors (IGFs) are bound by several IGF-binding proteins
      (IGFBPs) that appear to regulate IGF transportation, receptor binding and action.
      In adult human serum, most of IGFs are bound in a 150 kDa complex which could not
      cross the capillary wall. We measured IGF-I and IGFBPs in chyle by
      radioimmunoassay and western ligand blot. The concentration of IGF-I in chyle was
      only 15% of the corresponding serum level and most of IGF-I was found in 50 kDa
      complex. The IGFBPs profile in chyle, especially IGFBP-3, was different from that
      of serum. The concentration of IGFBP-3 in chyle was much less than in serum and
      the size of glycosylated IGFBP-3 was different from that of serum. However, the
      size and relative amount of IGFBP-1 and -2 in chyle were similar to serum. This
      finding indicates that IGF-I and IGFBPs in chyle to a large extent originate in
      the vascular system and only the 50 kDa complex can cross the capillary barrier.

PMID- 9539314
TI  - Immunohistochemical characterization of the cellular infiltrate in airway mucosa
      of toluene diisocyanate (TDI)-induced asthma: comparison with allergic asthma.
AB  - Toluene diisocyanate (TDI) is the most prevalent agent in occupational asthma
      (OA) in Korea. The immuno-pathologic mechanism for TDI-induced
      bronchoconstriction remains to be clarified. We studied the immunohistochemical
      finding of inflammatory cells in bronchial mucosa in subjects with TDI-induced
      asthma. Fiberoptic bronchial biopsy specimens were obtained from nine subjects
      with TDI-induced asthma. Six allergic asthma sensitive to house dust mite were
      enrolled as controls. Bronchial biopsy specimens were examined by immunohistology
      with a panel of monoclonal antibodies to mast cell tryptase (AA1), secretary form
      of eosinophil cationic protein (EG2), pan T-lymphocyte (CD3) and neutrophil
      elastase (NE). There was a significant increase in the number of AA1+, EG2+ and
      NE+ cells in TDI-induced asthma compared to those of allergic asthma (p=0.02,
      p=0.04, p=0.03, respectively). No significant differences were observed in the
      number of CD3+ cells (p=0.27). These findings support the view that neutrophil
      recruitment together with eosinophil and mast cell, may contribute to the
      bronchoconstriction induced by TDI.

PMID- 9539315
TI  - A study of the viral etiology of histiocytic necrotizing lymphadenitis (Kikuchi
      Fujimoto disease).
AB  - Histiocytic necrotizing lymphadenitis (HNL) or Kikuchi's disease is a
      distinctive, self-limited disorder characterized by necrotizing cervical
      lymphadenopathy in young individuals. HNL is more prevalent among Asians and is a
      relatively common disorder among Koreans. A preceding fever, lymphopenia, and
      occasional skin rashes suggest a viral etiology and there have been sporadic
      reports of viral association. However, so far, no infectious agent has been
      proven to be etiologically related. In the present study, the authors examined
      HNL tissue samples for the presence of the genome of herpesviridae. A polymerase
      chain reaction was performed on 12 freshly frozen lymph nodes with HNL with a
      single pair of consensus primers selected within a highly conserved region of the
      DNA polymerase gene of the Epstein-Barr virus (EBV), designed to detect herpes
      simplex type 1 (HSV1), herpes simplex virus type 2 (HSV2), and cytomegalovirus
      (CMV) in addition to EBV. The amplified products of known sizes were then
      analyzed by a single restriction enzyme treatment for confirmation. No viral DNA
      was amplified in any of the 12 cases of histiocytic necrotizing lymphadenitis.
      The authors conclude that there is no evidence that HSV1, HSV2, CMV, or EBV plays
      any role in the pathogenesis of histiocytic necrotizing lymphadenitis.

PMID- 9539316
TI  - Pathologic characteristics of primary cutaneous T-cell lymphoma in Korea.
AB  - Cutaneous T-cell lymphomas (CTCL) represent a heterogeneous group of peripheral T
      cell lymphomas arising in the skin and show considerable variations in
      clinicopathological features. This study was designed to examine viral genomes
      and cellular proliferation markers in CTCLs arising in Korea. On the basis of
      their morphologic characteristics and immunophenotypes, 43 cases of primary CTCL
      were classified, and evaluated for association with either HTLV-I or EBV, p53
      protein immunoreactivity and Ki-67 labeling index (LI). EBV was demonstrated in
      15 cases (35%) either by EBER in-situ hybridization or PCR; particularly high
      rates were exhibited by angiocentric T-cell lymphomas. PCR was used to detect
      HTLV-I proviral DNA, but none was found. The p53 expression rate was higher in
      large cell lesions, but the Ki-67 LI failed to show any significant differences
      among the different types. We therefore concluded that in Korea, HTLV-I is less
      frequently associated with CTCL than in other endemic countries. EBV was found
      particularly in angiocentric lesions, regardless of cell size or degree of
      pleomorphism. Because of its high positive rates in high grade lesions, the p53
      expression showed positive correlation with histologic grade; however, the Ki-67
      labeling index did not correlate with the histologic grade in CTCL.

PMID- 9539317
TI  - Arthritic manifestations of inflammatory bowel disease.
AB  - Inflammatory bowel disease (IBD) is commonly associated with arthritic
      manifestations. They are divided into three clinical categories; peripheral
      arthritis, spondylitis, and sacroiliitis. To evaluate the incidence of arthritis
      associated with IBD in Korea, we retrospectively reviewed one hundred and twenty
      nine patients with IBD, 77 with ulcerative colitis (UC) and 52 with Crohn's
      disease (CD). Arthritis occurred in twenty-two patients (17.1%); 15 with
      UC(19.6%), 7 with CD (13.5%). Patients with arthritis had more active
      inflammations and all were seronegative except one patient. Peripheral arthritis
      was found in twenty patients (15.5%) and more common in UC (19.6%) than in CD
      (9.6%). Joint involvements tended to be monoarticular or pauciarticular, and most
      frequently developed in the knee and ankle. Spondylitis was diagnosed in one
      patient (1.6%) who showed HLA B27 positivity. Radiographic sacroiliitis was
      observed in eight patients (6.2%) who revealed HLA B27 negativity. Both
      peripheral arthritis and sacroiliitis were found in six patients (4.6%). In CD,
      arthritis occurred in 20% of the patients with colonic involvement but in none of
      the patients without colonic involvement. In conclusion, arthritis was frequent
      in patients with IBD. Peripheral arthritis was more common in patients with UC
      than CD. All the patients with CD and arthritis had colonic involvement.

PMID- 9539318
TI  - Increased serum levels of mutant p53 proteins in patients with colorectal cancer.
AB  - We have examined the serum levels of the mutant p53 protein in patients with
      colorectal cancer preoperatively (n=50), and in patients with adenomatous polyp
      (n=13). Mutant p53 protein in patients after curative surgical resection of
      colorectal cancer (n=26, part of the fifty preoperative patients) was also
      measured. Serum samples were stored frozen at -70 degrees C until the time of
      analysis. We used the p53 mutant ELISA (QIA03, CALBIOCHEM) system. Serum levels
      of the mutant p53 protein in patients with colorectal cancer (mean=0.97+/-0.14
      ng/ml, ranged from 0.7 ng/ml to 1.37 ng/ml, n=50) were significantly greater than
      those in patients with adenomatous polyp (mean=0.73+/-0.06 ng/ml, ranged from
      0.69 ng/ml to 0.83 ng/ml) (p<0.001). There was a significant correlation between
      serum p53 levels and CA19-9 levels (p<0.01). Serum levels of the mutant p53
      protein prior to surgery (mean=0.97+/-0.13 ng/ml, n=26) significantly decreased
      after surgical resection of tumor (mean=0.82+/-0.07 ng/ml) (p<0.001, paired t
      test). These results suggest that mutant p53 protein might be used as a potential
      biomarker in the management of patients with colorectal cancer. Further study is
      warranted to establish its clinical significance.

PMID- 9539319
TI  - Localized in vivo proton spectroscopy of renal cell carcinoma in human kidney.
AB  - In order to obtain proton magnetic resonance spectra from the renal tumor in
      human kidney we performed localized magnetic resonance spectroscopy using a
      saddle-type flexible surface coil. Five patients biopsy-proven as renal cell
      carcinoma at different stages were put in supine/lateral position to minimize
      motion artifacts while acquiring the spectrum. Water-suppressed 1H spectra were
      obtained with localized stimulated echo acquisition mode (STEAM) (20/13.7/2200;
      TE/TM/TR) and point resolved spectroscopy (PRESS) (288/2200; TE/TR) sequences.
      The principal resonances in the tumor STEAM spectrum were sorbitol (3.85 ppm),
      trimethylamines (TMA) (3.25 ppm), two unidentified signals (2.8 and 2.2 ppm), and
      lipid (0.9-1.8 ppm). In the PRESS spectrum using a long echo time (288 ms), two
      well localized signals, TMA at 3.25 ppm and lactate at 1.35 ppm were observed
      from a patient with a tumor at advanced stage. Interestingly only TMA at 3.25 ppm
      was observed from the patient with a low grade tumor. The spectral patterns of
      the tumor patients were different from those of normal kidney.

PMID- 9539320
TI  - Human herpesvirus 8 in Kaposi's sarcoma and Kaposi's sarcoma-mimicking vascular
      tumors.
AB  - Kaposi's sarcoma (KS) had been a rare and unusual vascular tumor until a recent
      epidemic of a disseminated and fulminant form of KS in AIDS patients. Infectious
      agents have been suspected of causing KS, and recently partial genomic DNA
      sequences of human herpesvirus 8 (HHV8) have been identified in AIDS-associated
      KS lesions. Since then, genomic DNA sequences of HHV8 have been isolated in other
      forms of KS. Although the partial genomic DNA sequence of HHV8 was reported to
      be, if rare, identified in vascular tumors other than Kaposi's sarcoma (KS), the
      presence of HHV8 in a very large fraction of KS indicates that detection of HHV8
      by PCR is a useful auxiliary tool in differentiating KS from other KS-mimicking
      vascular tumors. We examined whether the 233-bp segment of the viral DNA was
      detected in Korean patients with KS and other KS-mimicking vascular tumors. HHV8
      sequences were identified in all of nine classic type of KS but not in three
      epithelioid hemangioendotheliomas and seven angiosarcomas. Our results confirm
      the relatively restricted distribution of HHV8 and also argue against the
      likelihood of secondary colonization of KS cells by HHV8.

PMID- 9539321
TI  - The causative organisms of bacterial meningitis in Korean children, 1986-1995.
AB  - Bacterial meningitis remains a serious cause of morbidity and mortality in
      childhood. Epidemiologic investigations have shown variability in disease risks
      among different populations and races. In Korea, however, basic epidemiologic
      information on bacterial meningitis in children is limited. The main purpose of
      this study was to analyze bacteriologically proven meningitis cases in terms of
      the relative frequency of causative organisms, mortality rate, and age
      distribution beyond the neonatal period. Data was obtained from the hospital
      records who had been diagnosed with bacterial meningitis at 13 general or
      university hospitals from 1986 through 1995. The patients had at least one
      positive CSF culture for bacteria. Of 140 cases of CSF culture-proven bacterial
      meningitis, 46.4% was < or =1 year, 62.1% was < or =2 years, 81.4% was < or =5
      years cumulatively. Streptococcus pneumoniae was the most common bacteria
      responsible for 48 (35.0%) of all cases regardless of age, followed by
      Haemophilus influenzae for 48 (34.3%) and Neisseria meningitidis for 8 (6.4%)
      patients. The case fatality rate was 20.0%, 17.1%, and 16.7% for N. meningitidis,
      S. pneumoniae, and H. influenzae, respectively. In conclusion, the most common
      organisms of culture-proven bacterial meningitis in the last 10 years have been
      S. pneumoniae, H. influenzae, and N. meningitidis in order of frequency. Further
      study should be extended to nation-wide epidemiologic evaluation to show the
      incidence of bacterial meningitis caused by these three important organisms.

PMID- 9539322
TI  - Brain tumor in the first year of life: a single institute study.
AB  - Brain tumors in infants present special diagnostic and therapeutic challenges. To
      figure out the clinical features, pathological classification of the tumors and
      the treatment outcome of infantile brain tumors, 458 children (age<16) with brain
      tumors were reviewed retrospectively. Among them 21 cases (4.6%) were diagnosed
      during the first 12 months of life. Two tumors were definitely of congenital
      origin. The majority of infants with brain tumors presented with increased
      intracranial pressure. Fourteen tumors were located at the supratentorial area.
      Sixteen cases had neuroepithelial tumors; astrocytoma (optic pathway),
      supratentorial primitive neuroectodermal tumor (PNET) and medulloblastoma were
      found in three cases each. There were two treatment-related mortalities. Compared
      with the outcomes in older children, the treatment outcome was poorer in
      medulloblastoma and the optic pathway glioma which showed a higher growth
      potential. Because of the limited application of postoperative adjuvant therapy,
      radical surgical removal played a more important role in this age group. The
      prognosis of patients in whom the tumors could not be totally removed, largely
      depended on the pathological malignancy of the tumors. Though the treatment
      outcome was not always dismal, immaturity of the brain, higher growth potential,
      perioperative risks, limitations in adjuvant therapy, and pessimistic attitude on
      the part of parents made management more challenging.

PMID- 9539323
TI  - Primary pulmonary sarcoma with morphologic features of biphasic synovial sarcoma:
      a case report.
AB  - We report an unusual primary case of pulmonary sarcoma that developed in the lung
      of a 36-year-old woman. The tumor had histologic, immunologic and ultrastructural
      features identical to those of biphasic synovial sarcoma of the soft tissue. It
      consisted of an intimate admixture of cytokeratin and epithelial membrane
      antigen(EMA)-positive neoplastic epithelial cells and vimentin-positive
      fibroblast-like spindle cells with areas of hyalinization. The patient had a
      lobectomy and showed no evidence of recurrence or tumor at other sites 15 months
      after surgery. This case is an useful addition to the small number of published
      reports on pulmonary synovial sarcoma. The distinctive features of this neoplasm
      allow it to be different from other types of primary and metastatic malignancies
      in the lung.

PMID- 9539324
TI  - Hemophagocytic syndrome associated with occult B-cell lymphoma: an autopsy case.
AB  - Hemophagocytic syndrome has been observed in various disorders, including
      malignant histiocytosis, peripheral T-cell lymphoma, and viral or bacterial
      infections. However, B-cell lymphoma has seldom been associated with
      hemophagocytic syndrome. We report a case of B-cell lymphoma that was associated
      with hemophagocytic syndrome. The diagnosis was not made until the time of
      autopsy.

PMID- 9539325
TI  - A case of type IIa early gastric cancer developed in pernicious anemia.
AB  - Pernicious anemia is an autoimmune disease characterized by a gastric mucosal
      defect which results in an insufficiency of intrinsic factor to facilitate the
      absorption of the physiologic amount of cobalamin. Increased risk of cancers of
      the stomach has been reported for patients with pernicious anemia. We report here
      a case of a 65 year old woman who had been diagnosed as having pernicious anemia
      16 months previously, was receiving monthly vitamin B12 injections, and developed
      early gastric cancer type IIa by routine follow-up gastroscopic examination. This
      patient underwent endoscopic mucosal resection for an early gastric cancer lesion
      with a free resection margin.

PMID- 9539326
TI  - A case of autoimmune cholangitis associated with Sjogren's syndrome and
      arthropathy.
AB  - Autoimmune cholangitis (AC) is a recently proposed entity that describes a
      specific group of patients presenting overlapping features of primary biliary
      cirrhosis (PBC) and autoimmune hepatitis. The disease is characterized by dinical
      cholestasis, high titer antinuclear antibody, negative antimitochondrial
      antibody, and histologically, findings of PBC coexisting with varying degrees of
      parenchymal inflammation. In this report, we describe a patient with Sjogren's
      syndrome who fulfilled the diagnostic criteria of AC associated with unique
      arthropathy compatible with arthritis of PBC. This case illustrates the unusual
      coexistence of two diseases that may share similar pathogenic processes.

PMID- 9539327
TI  - Ovarian sex cord tumor with annular tubules in a patient with Turner syndrome.
AB  - A case of ovarian sex cord tumor with annular tubules (SCTAT) in a 24-year old
      woman with Turner syndrome is presented. Close association of dysgenetic gonads
      and gonadoblastoma has been clearly documented, and there have been sporadic
      reports of patients with other gonadal tumors. To our knowledge, a case of SCTAT
      in a patient with 45,X/46,XX Turner syndrome has not been reported. On the basis
      of histopathologic, immunohistochemical, and ultrastructural findings, we suggest
      that the SCTAT originated from pluripotential stem cells of the gonads and
      differentiated into either granulosa cells or Sertoli cells. We postulate a
      possible relationship between the SCTAT and gonadoblastoma based on the
      morphologic resemblance and occurrence in dysgenetic gonads.

PMID- 9539328
TI  - A case of Farber lipogranulomatosis.
AB  - A 35 month old girl had suffered from painful joint contractures of the whole
      body since a few months after birth, and she gradually developed numerous
      periarticular and subcutaneous nodules, hoarseness, swallowing difficulty with
      recurrent respiratory infections, nystagmus, and mental and developmental
      retardation. She was misdiagnosed as having juvenile rheumatoid arthritis at
      several university hospitals. Serologic studies for rheumatoid arthritis were all
      negative. Radiologic findings of the whole body showed osteoporosis and bony
      erosions; on brain CT the brain was diffusely atrophied. On cine-esophagography
      barium refluxed into the nasopharynx. Light microscopically, the reticular dermis
      and subcutis were markedly thickened with hyalinized sclerotic collagen bundles.
      There were interstitial and perivascular aggregates of foamy histiocytes which
      were positive for CD-68 immunostaining. On electron microscopy, foamy histiocytes
      were packed with numerous membrane-bound inclusions having C-shaped or worm-like
      profiles in addition to many myelin figures, occasional lipid droplets and rare
      banana-like bodies.

PMID- 9539329
TI  - A case of central pontine and extrapontine myelinolysis with early
      hypermetabolism on 18FDG-PET scan.
AB  - We report a 63 year-old woman who developed central pontine and extrapontine
      myelinolysis after rapid correction of hyponatremia. Lesions on brain MRI showed
      hypermetabolism on 18FDG-PET scan in the early stage of the disease and became
      hypometabolic on the follow-up scan. We suggest that active microglia and
      astrocytes are the main cause of the increased glucose metabolism.

PMID- 9539330
TI  - The current model of basal ganglia organization under scrutiny.

PMID- 9539331
TI  - Genetic aspects of Parkinson's disease.

PMID- 9539332
TI  - P450 enzymes and Parkinson's disease: the story so far.
AB  - Environmental or endogenous toxins may cause nigral cell death in Parkinson's
      disease (PD) as a result of genetic susceptibility conferred by altered
      expression of P450 enzymes. Attention over the last 10 years has focused on
      CYP2D6 polymorphisms and susceptibility to PD. This review summarizes reports
      arising from both phenotypic and genotypic studies involving CYP2D6 and PD.
      Phenotypic studies have failed to support a link between CYP2D6 and PD. The more
      powerful genetic studies initially indicated a link between CYP2D6B mutations and
      PD, but critical analysis of the literature and recent studies emerging from
      independent laboratories fail to confirm this. Mutations in CYP2D6B are also not
      implicated in familial PD. As yet, there is no conclusive evidence to suggest
      that CYP2D6 polymorphisms confer susceptibility to PD. Whether polymorphisms in
      other P450s (for example, CYP1A1 and CYP2E1) are implicated in PD remains to be
      established.

PMID- 9539333
TI  - Glial pathology but absence of apoptotic nigral neurons in long-standing
      Parkinson's disease.
AB  - The cause and mechanism of neuronal cell death in the substantia nigra of
      patients with Parkinson's disease (PD) are unknown. There is also controversy
      about whether the cell death results from a single event followed by cell loss
      consistent with aging or whether there is an ongoing pathologic process. Using
      postmortem tissue obtained from the Parkinson's Disease Society Brain Tissue Bank
      in London, we have sought to establish whether apoptosis, or more specifically
      DNA fragmentation of neurons, is a prominent feature of nigral pathology. In
      addition, we have studied microglial activation in the substantia nigra as an
      indicator of ongoing pathology using the highly sensitive markers CR3/43 and
      EBM11. Reactive astrocytes have been assessed using immunostaining for glial
      fibrillary acidic protein (GFAP). Ten patients with pathologically proven PD were
      studied. In all cases, regardless of disease duration, severity, drug treatment,
      or age of the patient, there was no evidence of apoptosis in the substantia nigra
      as assessed by in situ end-labeling of DNA fragments using biotinylated dUTP and
      terminal deoxynucleotidyl transferase (TdT). In contrast, a case of multiple
      system atrophy (MSA) served as a positive control for the technique. In this
      case, positive DNA end-labeling could be found in neurons and non-neuronal cells
      in the brain stem. In the PD cases, there was, however, localized pathology in
      the substantia nigra as revealed by the CR3/ 43 and EBM11 markers for activated
      microglia. This process seemed independent of disease duration and was florid
      even in patients with severe neuronal loss. It remains to be determined to what
      extent the activation of glial cells reflects progressive nigral pathology, and
      whether those factors which are classically associated with prominent apoptotic
      neuronal cell death in vivo, such as neurotrophic factor deprivation, are prime
      causes of nigral neuronal loss in PD. Future studies should focus on recent-onset
      PD or incidental Lewy body disease to further address these questions.

PMID- 9539334
TI  - Kappa-opioid receptor agonists increase locomotor activity in the monoamine
      depleted rat model of parkinsonism.
AB  - Excessive glutamate transmission in the basal ganglia is a major factor in the
      neural mechanisms underlying parkinsonian akinesia. Activation of kappa opioid
      receptors causes a presynaptic reduction in glutamate release. Kappa opioid
      receptors are concentrated in those regions of the basal ganglia associated with
      increased glutamate transmission in parkinsonism. In this study, we use the alpha
      methyl-p-tyrosine and reserpine-treated rat model of parkinsonism to investigate
      whether systemic administration of the kappa opioid agonists enadoline (CI-977)
      and U69,593 can alleviate the symptoms of parkinsonism either alone or in
      conjunction with dopamine replacement therapy. We report that, when administered
      alone, both enadoline and U69,593 can increase locomotion in monoamine-depleted
      rats. No increase in locomotor activity was seen after kappa opioid agonist
      administration in non-parkinsonian rats. The responses to kappa opioid agonists
      were blocked by co-administration of either the nonspecific opioid receptor
      antagonist naloxone or the selective kappa opioid receptor antagonist nor
      binaltorphimine (nor-BNI). An important finding is that when enadoline and L-dopa
      are administered together, their anti-akinetic properties are synergistic. Thus,
      the doses of enadoline and L-dopa required to alleviate akinesia when
      administered together are lower than either administered alone. These data
      illustrate the importance of kappa opioid receptors in the neural mechanisms
      controlling voluntary movement and suggest that kappa opioid agonists may have a
      role as adjuncts to dopamine replacement in the management of Parkinson's
      disease.

PMID- 9539335
TI  - De novo administration of ropinirole and bromocriptine induces less dyskinesia
      than L-dopa in the MPTP-treated marmoset.
AB  - In contrast to levodopa (L-dopa), de novo administration of the D2-like receptor
      agonist bromocriptine to patients with Parkinson's disease (PD) or to 1-methyl-4
      phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated subhuman primates is not
      associated with the onset of significant dyskinesia. We now compare the ability
      of the novel D2-like selective dopamine agonist ropinirole with that of
      bromocriptine and L-dopa to induce dyskinesia in MPTP-treated common marmosets.
      MPTP-treated common marmosets were treated with placebo, L-dopa plus carbidopa,
      ropinirole, or bromocriptine daily for 30 days (n = 4 per group) in doses that
      were titrated to similarly increase locomotion and improve motor disability. L
      dopa rapidly induced dyskinesia of moderate to severe intensity, whereas
      ropinirole and bromocriptine produced mild dyskinesia over the course of the
      study that was significantly less severe than in the L-dopa-treated group (p <
      0.05). However, in a separate group of marmosets previously primed with L-dopa to
      exhibit dyskinesia, ropinirole administration elicited severe dyskinesias
      comparable with that of L-dopa in a dose-dependent fashion. Ropinirole, in common
      with bromocriptine, has a lesser tendency than L-dopa to produce dyskinesia while
      similarly improving motor performance in drug-naive MPTP-treated marmosets.
      However, in common with other dopamine agonists, ropinirole will elicit
      comparable dyskinesia once L-dopa priming has occurred. These results predict a
      similar response to ropinirole and other long-acting dopamine agonists in L-dopa
      naive patients with PD and emphasize the importance of avoiding initial
      dyskinesia induction through early use of dopamine agonist drugs.

PMID- 9539336
TI  - Apomorphine enantiomers protect cultured pheochromocytoma (PC12) cells from
      oxidative stress induced by H2O2 and 6-hydroxydopamine.
AB  - A significant body of evidence has been provided to support the hypothesis that
      oxidant stress may be responsible for the degeneration of dopaminergic neurons in
      the substantia nigra pars compacta in Parkinson's disease. Apomorphine, a
      dopamine D1/D2-receptor agonist in the clinical therapy of Parkinson's disease,
      has been found to be a potent antioxidant and to prevent free radical reaction in
      rat brain mitochondrial fraction. In this article we show that 1-10 microM of
      apomorphine protects rat pheochromocytoma (PC12) cells from the toxic effects of
      H2O2 (0.6 mM) and the neurotoxin 6-hydroxydopamine (150 microM). These effects
      were not exhibited by ascorbic acid, desferal, lisuride, or bromocriptine.
      Although pergolide exhibited some protection of PC12 cells against H2O2 toxicity,
      it was not as potent as apomorphine. In light of the present findings and the
      clinical reports that parkinsonian patients on long-term apomorphine stabilize
      clinically and can be weaned off L-dopa, one may assume that apomorphine can
      exert a neuroprotective activity via its potent antioxidant properties.

PMID- 9539337
TI  - Costs of drug treatment in Parkinson's disease.
AB  - Parkinson's disease (PD) has a major socioeconomic impact on society. The
      chronic, progressive course of the disease, which often leads to severe
      disability, results in high expenses for the medical resources used for
      treatment, care, and rehabilitation of patients as well as reduced or lost
      productivity as a result of illness or premature death. In Great Britain, it has
      been estimated that the National Health Service spends up to 383 million pound
      sterling (1992) annually for the care of PD. This emphasizes the importance of
      assessing the costs related to this disease. A detailed knowledge of the cost
      allocation would provide a solid basis on which health care priorities can be
      rationally set. Next to hospitalization, drug treatment accounts for the highest
      expense for direct medical costs of PD. Therefore, this analysis focuses on the
      costs of drug treatment for PD. The cost analysis was based on a retrospective
      study of 409 patients with PD who were seen over a 1-year period in our movement
      disorders clinic. The cost of therapy varied considerably depending on the
      severity of the condition (assessed in the "off" phase), the incidence of motor
      fluctuations, and the type of PD. In the early stage of the disease (Hoehn and
      Yahr stage I [HY I]), mean daily costs for therapy were DM (German marks) 6.60,
      which increased in later stages of the disease (HY V) to DM 22.00. If rare cases
      requiring continuous subcutaneous apomorphine infusion were included, mean daily
      costs of patients in HY V rose to DM 32.50 (the mean daily costs of subcutaneous
      apomorphine-treated patients in HY V: DM 74.30). Patients with motor fluctuations
      accounted for higher costs (DM 16.50) compared with those without motor
      fluctuations (DM 7.80). With respect to the three subtypes of PD, the mean daily
      expenditure was DM 7.00 for the tremor-dominant type, DM 12.40 for the akinetic
      rigid type, and DM 10.80 for the mixed type. In the group of 409 PD patients
      included in this analysis, the average daily expenditure for drug treatment
      totaled DM 10.70 per patient (including patients on subcutaneous apomorphine).

PMID- 9539338
TI  - Influence of body load on the gait pattern in Parkinson's disease.
AB  - The influence of body unloading (to 75, 50, and 25% body weight) on lower leg
      muscle activation during treadmill walking was investigated in patients with
      Parkinson's disease, age-matched and young healthy subjects. The aim of the study
      was to test the hypothesis that patients suffer from impaired extensor load
      receptor function. Although lower leg flexor muscle electromyographic (EMG)
      activity was relatively independent of body load, lower leg extensor EMG activity
      was markedly load sensitive. The EMG amplitude of the latter decreased with body
      unloading during stepping in all three groups of subjects. The load sensitivity
      progressively increased from patients to age-matched to young healthy subjects.
      In addition, the absolute level of leg extensor EMG amplitude during the stance
      phase of stepping became progressively larger from patients to age-matched
      subjects to young healthy subjects. It is suggested that decreased sensitivity of
      extensor load reflex mechanisms contributes to impaired gait in elderly subjects
      and is more pronounced in parkinsonian patients.

PMID- 9539339
TI  - Late components of the event-related potentials and their topography in
      Parkinson's disease.
AB  - Late components of the event-related potential (ERP; N100, P200, N200, and P300)
      were elicited using an auditory oddball paradigm (with a button-press response to
      target stimuli) in 15 Parkinson's disease (PD) patients and 50 normal control
      subjects. Compared with control subjects, PD subjects showed a significant
      decrease in N200 amplitude. Between-group topographical differences in N200
      amplitude were evident at central (C3, Cz, C4) and temporal (T5, T3, T4, T6)
      regions. The results may reflect a deficit in response selection in PD possibly
      resulting from a dysfunction associated with the abnormalities in the central and
      temporal regions found to have a decreased N200 amplitude compared with normal
      control subjects in this study.

PMID- 9539340
TI  - Differential diagnosis of parkinsonism with [18F]fluorodeoxyglucose and PET.
AB  - The clinical differentiation between typical idiopathic Parkinson's disease (IPD)
      and atypical parkinsonian disorders (APD) is complicated by the presence of signs
      and symptoms common to both forms of parkinsonism. Metabolic brain imaging with
      [18F]fluorodeoxyglucose (FDG) and positron emission tomography (PET) may be a
      useful adjunct in differentiating APD from IPD. To explore this possibility, we
      studied 48 parkinsonian patients suspected as having possible APD because of a
      deteriorating response to dopaminergic treatment, the development of autonomic
      dysfunction, or both. A group of 56 patients with likely IPD served as control
      subjects. We used quantitative FDG/PET to measure regional rates of cerebral
      glucose use in IPD and APD patients. We used discriminant analysis to categorize
      IPD and APD patients based on their regional metabolic data. We found that a
      linear combination of caudate, lentiform, and thalamic values accurately
      discriminated APD from IPD patients (p < 0.0001). Significant metabolic
      abnormalities were present in the striatum and the thalamus of 36 of 48 (75%) APD
      patients. Our findings show that measurements of regional glucose metabolism can
      be used to discriminate patients with suspected APD from their counterparts with
      classic IPD. FDG/PET may be a useful adjunct to the clinical examination in the
      differential diagnosis of parkinsonism.

PMID- 9539341
TI  - Asymmetry of basal ganglia glucose metabolism and dopa responsiveness in
      parkinsonism.
AB  - We investigated, by positron emission tomography (PET) with [18F]fluoro-2-deoxy-d
      glucose (FDG) (FDG-PET), brain glucose metabolism in 19 patients with
      parkinsonian features. We compared local pattern of FDG uptake and asymmetry
      indexes in patients with therapeutic response to levodopa (L-dopa) (group 1,
      presumed Parkinson's disease, n = 9) and patients without L-dopa therapeutic
      response (group 2, presumed striatonigral degeneration, n = 10). Limb dystonia
      was present in 11% of patients in group 1 and in 40% of patients in group 2.
      Asymmetry in basal ganglia metabolism was distributed differently in the two
      groups (analysis of variance, p < 0.04). In superior and inferior putamen,
      superior and middle caudate, ventral striatum, and inferior thalamus, relative
      reduction in metabolism on the side contralateral to predominant parkinsonian
      signs was associated with L-dopa unresponsiveness. On the contrary, in middle
      caudate, ventral striatum, and inferior thalamus, a relative increase in
      metabolism on the side contralateral to the predominant side, parkinsonian signs
      were found in L-dopa-responsive patients. Our FDG-PET study using simple
      statistical procedures demonstrates inverse asymmetry of basal ganglia glucose
      metabolism in parkinsonian patients grouped on the sole basis of L-dopa
      responsiveness.

PMID- 9539342
TI  - Increasing striatal iron content associated with normal aging.
AB  - Free-radical-mediated mechanisms may contribute to neuronal damage in Parkinson's
      disease (PD), other neurodegenerative conditions also associated with aging, and
      the aging process itself. Cytotoxic free radicals are generated in the brain by
      oxidation/reduction reactions that are catalyzed by transition metals such as
      iron. Any regional increase in brain iron concentration may increase the
      potential for local free-radical formation. The purpose of this study was to
      determine the relationship between age and basal ganglia iron content in 20
      normal individuals ranging from 24 to 79 years of age. We used an in vivo
      magnetic resonance method to quantify the effects of paramagnetic centers
      sequestered inside cellular membranes, thereby enabling the determination of a
      quantitative index of local brain iron content. We observed a strong direct
      relationship between age and regional iron content in the putamen (r = 0.76, p <
      0.0001) and caudate (r = 0.69, p < 0.001), but not in the globus pallidus (r =
      0.32, p = 0.17) or thalamus (r = 0.13, p = 0.58). In conclusion, striatal iron
      content increases with advancing age. This increase may increase the probability
      of free-radical formation in the striatum, therefore representing a risk factor
      for the development of neurodegenerative disorders such as PD in which
      nigrostriatal neurons may be affected by increased oxidant stress.

PMID- 9539343
TI  - Reliability between two observers using a protocol for diagnosing essential
      tremor.
AB  - Protocols with demonstrated reliability have been established for the diagnosis
      of numerous movement disorders. whereas in the essential tremor (ET) literature,
      there is no discussion about the reliability of diagnostic protocols. Lack of
      knowledge of the reliability of diagnostic protocols in ET limits the use of
      these protocols because reliability is an essential requirement for scientific
      quality in data management. The objective of this study was to determine the
      reliability of a protocol for diagnosing ET. The protocol consists of a Tremor
      Interview, a videotaped Tremor Examination, and a diagnostic algorithm. Eighty
      three subjects with ET, identified in a community-based health study in
      Washington Heights-Inwood, New York, were matched with 83 control subjects from
      the same community. These subjects and their relatives are being recruited to
      participate in the Washington Heights-Inwood Genetic Study of ET. Two hundred
      twenty-six subjects have been evaluated to date (35 ET cases, 40 controls, 151
      relatives). All 226 underwent an 84-item Tremor Interview and 26-item videotaped
      Tremor Examination. Diagnoses (normal, possible ET, probable ET, definite ET)
      were independently assigned by two blinded neurologists specializing in movement
      disorders. The kappa statistic, k, was used to determine diagnostic agreement
      between these two neurologists. The concordance rate between two raters using
      diagnostic categories definite ET, probable ET. possible ET, and normal was 80%;
      kw = 0.84 (near perfect to perfect agreement). The concordance rate between two
      raters using two diagnostic categories (definite ET and normal) was 100%; k =
      1.00 (perfect agreement). There was high correlation between the two raters'
      total tremor scores (r = 0.89, p < 0.00001). This diagnostic protocol is highly
      reliable. Research in ET would greatly benefit from diagnostic protocols with
      demonstrated reliability.

PMID- 9539344
TI  - Diagnostic and pathophysiological aspects of psychogenic tremors.
AB  - Psychogenic tremor has become a rare movement disorder. Twenty-five patients from
      our movement disorder unit presented either with obviously nonorganic body
      shaking during stance or with extremity tremors. A sudden onset and a variable
      but rarely remitting course of the condition was common. The "coactivation sign
      of psychogenic tremor" and absent finger tremor were the most consistent criteria
      to separate them from organic tremors. Quantitative analysis of tremor shows
      decreasing amplitudes in most organic tremors when the extremity is loaded with
      additional weights. In contrast, we found an increase of tremor amplitude for
      most of the cases with psychogenic tremor. This might be caused by increased
      coactivation to maintain the oscillation. These clinical and electrophysiological
      features suggest a clonus mechanism induced by coactivation as the
      pathophysiological basis of psychogenic extremity tremor. Psychiatric evaluation
      did not show overt signs of hysteria for the majority of the patients. However,
      we found depression and functional somatic or psychosomatic conditions to be
      frequent among the patients. A reduced ability to cope with stressful situations
      may play a significant role. The clinical course of the condition is usually far
      from benign. We conclude that psychogenic tremor can be positively diagnosed by
      means of neurologic signs in the majority of patients and is not only a diagnosis
      of exclusion. The poor outcome makes early and serious neuropsychiatric attempts
      at therapy necessary.

PMID- 9539345
TI  - X-linked Dystonia-Deafness syndrome.
AB  - We report a family with early-onset deafness and progressive dystonia exclusively
      involving males over two successive generations. There is also evidence of
      cognitive impairment and corticospinal tract involvement. The pedigree suggests
      an X-linked inheritance. A similar family was originally described by Scribanu
      and Kennedy. Tranebjaerg et al. have recently reported two other families with
      linkage to Xq22 and also proposed a novel X-linked candidate gene. These findings
      support the existence of a distinct neurodegenerative syndrome principally
      characterized by early-onset deafness and progressive dystonia. Neuropathology of
      one case showed a mosaic pattern of neuronal loss and gliosis in the caudate and
      putamen suggesting that this pattern is not restricted to XDP or Lubag.

PMID- 9539346
TI  - Increased activation of frontal areas during arm movement in idiopathic torsion
      dystonia.
AB  - Most positron emission tomography (PET) studies of regional cerebral function in
      idiopathic torsion dystonia (ITD) have failed to show abnormalities, but there
      have been few studies of the changes in regional cerebral blood flow (rCBF) that
      occur during movement in dystonia. Using PET, we have studied six patients with
      familial generalized ITD both at rest and while moving a joystick with the right
      hand. The patterns of CBF change obtained were compared with those in six age
      matched control subjects. In the dystonia group, free selection of movement was
      associated with relative increases in rCBF above that observed in control
      subjects in the left premotor area, the supplementary motor area (SMA), the
      anterior cingulate cortex, and the left dorsolateral prefrontal area. Subcortical
      increases were observed within the cerebellum and the putamen. There was a
      relative decrease in flow through the contralateral primary sensorimotor cortex.
      These findings contrast with those reported in patients with Parkinson's disease
      undertaking the same task in which the activity in the SMA and putamen was
      decreased. We suggest that arm dystonia in ITD is associated with overactivity of
      the premotor areas, including the SMA, and that this results from release of the
      thalamus from the normal inhibitory influence of the globus pallidus internal
      segment. Other abnormalities of basal ganglia control of brain stem centers may
      be involved in axial dystonia.

PMID- 9539348
TI  - Immobilization tests and periodic leg movements in sleep for the diagnosis of
      restless leg syndrome.
AB  - Patients with restless leg syndrome (RLS) complain of motor restlessness, usually
      occurring while they rest in the evening. Two immobilization tests have been
      described to assess leg restlessness in these patients. In the first test, the
      patient sits in bed with his or her legs outstretched while electromyograms are
      recorded from right and left anterior tibialis muscles for an hour (Suggested
      Immobilization Test [SIT]); in the second test, the legs are immobilized in a
      stretcher (Forced Immobilization Test [FIT]). In the current study, the SIT and
      the FIT were compared in patients with RLS and normal control subjects matched
      for age and sex. More leg movements were seen in patients than in controls during
      immobilization tests, especially the SIT. These movements were periodic,
      occurring at a frequency of approximately one every 12 seconds. The SIT (index >
      40) was found to discriminate between RLS and control subjects better than the
      FIT (index > 25). Patients were also recorded during two consecutive nights to
      measure periodic leg movements in sleep (PLMS). A SIT index greater than 40 and a
      PLMS index greater than 11 (highest PLMS index of 2 consecutive nights) were
      found to discriminate patients with RLS from control subjects with similar power.
      With each of these two measures, the clinical diagnosis was correctly predicted
      in 81% of patients and 81% of the control subjects. The SIT has several
      advantages over the measure of the PLMS index; it does not require an all-night
      polygraphic recording and can be administered several times a day to measure
      circadian fluctuation of motor restlessness.

PMID- 9539347
TI  - Imaging the pre- and postsynaptic side of striatal dopaminergic synapses in
      idiopathic cervical dystonia: a SPECT study using [123I] epidepride and [123I]
      beta-CIT.
AB  - There is increasing evidence that a dysfunction of the dopaminergic system may be
      involved in the pathogenesis of idiopathic dystonia. To visualize possible
      alterations of the pre- and postsynaptic side of striatal dopaminergic synapses,
      SPECT studies using the radiotracers [123I] epidepride and [123I] beta-CIT were
      performed in 10 patients with idiopathic cervical dystonia. Eleven age- and sex
      matched subjects served as controls. [123I] Epidepride is a new highly affine
      marker of D2 receptors, and [123I] beta-CIT binds to dopamine transporters on
      dopaminergic nerve endings. [123I] Epidepride binding was significantly reduced
      in both striata of dystonia patients compared with controls (p < 0.05). In
      contrast, striatal [123I beta-CIT uptake did not differ from controls. We
      conclude that dopaminergic dysfunction in idiopathic focal dystonia mainly
      involves postsynaptic mechanisms and suggest a disturbance of the indirect
      pathway of the motor circuit resulting in a disinhibited thalamocortical
      stimulation.

PMID- 9539349
TI  - The offset cortical potential: an electrical correlate of movement inhibition in
      man.
AB  - Nine normal subjects were asked to make either a brisk isometric pinch of a force
      transducer held between the forefinger and thumb, or to hold a pinch for
      approximately 15 s and then release the force suddenly without any overt
      antagonist contraction. EEG activity was averaged about the onset or offset of
      EMG activity, and movements were made in the subjects' own time. All subjects
      found the task simple. The EEG activity preceding offset of contraction (offset
      cortical potential) was significantly smaller in lateral leads than that seen
      before onset of contraction. Midline activation was similar in both tasks. We
      suggest that in the onset task, motor cortex activity related to the act to be
      performed contributes substantially to the EEG potentials in lateral leads. This
      activity is absent in the offset task which requires only withdrawal of tonic
      input to motor cortex. Midline activity, common to both onset and offset tasks,
      could reflect timing, attentional, or other processes. The results are discussed
      in relation to previous data from an isotonic relaxation task.

PMID- 9539351
TI  - Generalized chorea in two patients harboring the Friedreich's ataxia gene
      trinucleotide repeat expansion.
AB  - Recently, a trinucleotide repeat expansion in intron 1 of the frataxin gene on
      chromosome 9p13 has been identified as the genetic defect in Friedreich's ataxia
      (FA). We have identified two patients exhibiting generalized chorea in the
      absence of cerebellar signs who were homozygous for this intron 1 expansion.
      Chorea as a rare manifestation of FA has previously been controversial. This is
      the first report of chorea in patients confirmed to have the FA genetic
      abnormality and broadens further the clinical phenotype associated with the FA
      genotype.

PMID- 9539350
TI  - Ten years' experience with enteral levodopa infusions for motor fluctuations in
      Parkinson's disease.
AB  - We report our long-term experience using enteral levodopa infusions in 22
      patients with Parkinson's disease and severe motor fluctuations. Amelioration of
      intractable dyskinesias was the most important factor that determined whether
      patients chose to continue using the infusion pump system. Mechanical and
      physical problems associated with enteral access were the most common reasons for
      which patients discontinued pump use. Nearly all patients continued to have
      dramatically increased on time for the duration of follow up, suggesting that
      technically less-cumbersome systems that provide continuous dopaminergic
      stimulation are worthwhile and should be developed.

PMID- 9539352
TI  - Verapamil for severe hyperkinetic movement disorders.
AB  - The use of verapamil in three cases of severe hyperkinetic movement disorders
      resulted in dramatic improvement in patients who had been refractory to many
      other treatments over a prolonged period. A videotape illustration of one of the
      patients is provided. The mechanism of action and evidence of efficacy of calcium
      channel blockers for abnormal movements are discussed.

PMID- 9539353
TI  - Functional improvement in a patient with cerebral calcinosis using a
      bisphosphonate.
AB  - Idiopathic cerebral calcification can be associated with a progressive neurologic
      disorder for which there is no known treatment. This report describes a patient
      with a familial form of this disorder presenting in middle age with progressive
      Parkinson-like features along with spasticity, dystonia, and ataxia. Disodium
      etidronate, a bisphosphonate, produced a two-fold improvement in the rate of his
      speech and gait, but did not affect his spasticity, dystonia, or ataxia.
      Quantitative analysis of cerebral calcification did not reveal any reduction in
      the amount of calcification, suggesting other possible mechanisms for this
      clinical improvement.

PMID- 9539354
TI  - Arm tremor secondary to Wilson's disease.

PMID- 9539356
TI  - Cortical action tremor and focal motor seizures after parietal infarction.

PMID- 9539355
TI  - Square-wave action dystonia in Parkinson's disease.

PMID- 9539357
TI  - Posthypoxic midbrain tremor.

PMID- 9539358
TI  - Hyperthyroidism presenting as recurrent short paroxysmal kinesigenic dyskinesia.

PMID- 9539359
TI  - Repetitive belching, aerophagia, and torticollis in Huntington's disease: a case
      report.

PMID- 9539360
TI  - Is levodopa toxic to human substantia nigra?

PMID- 9539361
TI  - P-selectin expression in canine cutaneous inflammatory diseases and mast cell
      tumors.
AB  - P-selectin, a member of the selectin family of adhesion molecules, mediates the
      initial adhesion of leukocytes to the blood vessel wall during their emigration
      from the circulation. Adhesion molecules play an important role in the
      pathogenesis of several diseases, including various skin conditions. The
      objectives of the present study were to characterize the expression of vascular P
      selectin in the skin of dogs suffering from inflammatory diseases or from common
      cutaneous neoplasms, and to determine if a correlation exists between P-selectin
      expression and inflammatory cell infiltration in these conditions.
      Immunohistochemistry was performed on formalin-fixed canine skin using a specific
      anti-canine P-selectin monoclonal antibody (MD3). Results showed that P-selectin
      was minimally expressed in normal canine skin. However, the number of P-selectin
      expressing blood vessels was significantly increased (P < 0.05) in cases of
      allergic dermatitis, autoimmune dermatitis, pyogranulomatous dermatitis,
      dermatophytosis, and panniculitis. Highest P-selectin expression (percentage of
      MD3-positive vessels and intensity of the reaction) was observed in cases of
      autoimmune and pyogranulomatous dermatitis (55.3+/-7.4 and 44.0+/-9.9% P-selectin
      positive vessels, respectively). In all conditions studied, a positive
      correlation existed between the number of P-selectin-positive blood vessels and
      the number of infiltrating leukocytes (r=0.556, P < 0.01). A significant number
      of blood vessels in mast cell tumors also expressed P-selectin, whereas no
      staining was observed in any of the histiocytomas examined. These results reveal
      that P-selectin expression is increased in different types of canine inflammatory
      skin diseases and suggest that P-selectin could participate in the local
      recruitment of leukocytes in canine cutaneous diseases.

PMID- 9539362
TI  - Functional loss of p21/Waf-1 in a case of benign canine multicentric melanoma.
AB  - Mutations of tumor suppressor genes remove mechanisms that normally arrest
      proliferation of transformed cells, resulting in tumor formation. The p53 gene
      product functions as a tumor suppressor that induces p21/Waf-1, the 21-kDa
      product of the waf-1/cip-1/mda-6 gene. p21/Waf-1 is a pan-cyclin-dependent kinase
      inhibitor that arrests cell cycle progression under a variety of circumstances.
      We examined tissues from a dog with multiple primary pigmented proliferative
      lesions (benign, multicentric melanoma consisting of three distinct dermal
      lesions and a matrical cyst) for p21/Waf-1 and p53 expression by
      immunohistochemistry and immunoblotting. p21/Waf-1 and p-53 proteins were
      undetectable in the tumor cells and in the cyst but were present in adjacent
      normal tissues. Abundant cyclin-dependent kinase 4 (Cdk4), a protein related
      functionally to p21/Waf-1, also was present in the cyst. A somatic mutation of
      the waf-1 gene or of the p53 gene may have resulted in the loss of p21/Waf-1
      expression in a common precursor of pigment-producing cells from the affected
      dog. Furthermore, this functional loss of p21/Waf-1 may play an important role in
      the genesis of canine benign melanoma.

PMID- 9539363
TI  - Acute stress causes skin ulceration in striped bass and hybrid bass (Morone).
AB  - Exposure of striped bass (Morone saxatilis) and hybrid bass (M. saxatilis female
      x Morone chrysops male) to an acute (2-hour) confinement stress caused skin
      ulceration on the fins but not on the body of all confined fish. Striped bass
      displayed more severe lesions than did hybrid bass. Histologically, lesions had
      varying degrees of epithelial erosion and ulceration, which was most severe at
      the distal portion of the fins. Ulceration was associated with dermal and
      hypodermal edema and necrosis of the remaining stromal tissue and tips of bone in
      the fin rays. No hemorrhage or thrombosis was present to suggest any obvious
      vascular derangement. No evidence was found for either trauma or an infectious
      agent initiating the lesions. Injecting fish with epinephrine caused a similar
      response, although the degree of ulceration was less severe. These findings may
      explain why many opportunistic skin pathogens can rapidly develop into serious
      infections in fish.

PMID- 9539364
TI  - Cutaneous and systemic necrotizing vasculitis in swine.
AB  - A systemic vasculitis involving particularly the skin and kidneys has been
      recently described in swine under the name dermatitis/nephropathy syndrome.
      Twelve pigs with gross cutaneous lesions typical of this condition were
      necropsied, and morphologic, immunohistochemical, microbiologic, and
      epidemiologic characteristics were studied. The pigs were divided into three
      groups comprising eight pigs with acute lesions, two with chronic lesions, and
      two with acute lesions kept for sequential skin biopsies. Acute skin lesions
      consisted of round to irregular, red to purple macules and papules that often
      coalesced to form large, irregular patches and plaques. With time, the lesions
      became covered by crusts and faded gradually, sometimes leaving scars.
      Characteristic distribution included the perineal area of the hindquarters,
      limbs, dependent parts of the abdomen and thorax, and margins of the ears. In the
      acute phase of the disease, necrotizing and leucocytoclastic vasculitis of small
      caliber blood vessels were observed within the dermis and panniculus and in
      various extracutaneous locations such as the renal pelvis and synovial membranes.
      All pigs had macroscopic evidence of pneumonia and generalized lymphadenopathy.
      Microscopically, they had interstitial pneumonia and perivascular cuffing of
      mononuclear cells in various tissues including skin. The presence of
      immunoglobulins and complement was demonstrated by immunofluorescence in and
      around necrotic vessels of the skin in the early stages. Porcine reproductive and
      respiratory syndrome (PRRS) virus (PRRSV) antigens were detected by
      immunohistochemistry in macrophages located around vessels of the tissues
      examined (skin and kidneys) in acute and chronic cases. PRRSV RNA was
      demonstrated by reverse transcription-polymerase chain reaction in lung and
      spleen homogenates from all pigs. The PRRSV was isolated in cell culture from 11
      of the pigs. These findings suggest that PRRSV infection may play a role in the
      pathogenesis of this systemic vascular disease of swine.

PMID- 9539366
TI  - Expression of the neutrophil chemoattractant interleukin-8 in the lesions of
      bovine pneumonic pasteurellosis.
AB  - We investigated the expression of interleukin-8 (IL-8) in pneumonic
      pasteurellosis of cattle because neutrophils are important mediators of tissue
      injury in this disease and because IL-8 is a major neutrophil chemoattractant in
      other species. We also compared IL-8 expression in bacterial and viral pneumonia,
      since the latter lacks the severe neutrophil exudation typical of pneumonic
      pasteurellosis. IL-8 expression was assessed by northern analysis, in situ
      hybridization, enzyme-linked immunosorbent assay, and in vivo bioassay. IL-8 mRNA
      expression was elevated dramatically in lesions of pneumonic pasteurellosis
      compared to unaffected lung from the same calves. In situ hybridization revealed
      intense expression of IL-8 mRNA in alveolar macrophages and neutrophils and
      milder expression in bronchiolar and alveolar epithelium, interstitial cells, and
      pleural mesothelium. Bronchoalveolar lavage fluid from lesional lung contained
      16.06+/-4.00 ng/ml IL-8, whereas those from nonlesional and normal lung contained
      0.34+/-0.11 and 0.01+/-0.002 ng/ml, respectively. We detected IL-8 expression at
      only minimal levels in bovine respiratory syncytial viral pneumonia. Lung
      extracts from lesions of pneumonic pasteurellosis induced vigorous neutrophil
      infiltration following injection into bovine skin, and 89% depletion of IL-8 from
      the extract reduced this neutrophil influx by 60%. These results demonstrate
      consistent upregulation of IL-8 expression in lesions of pneumonic
      pasteurellosis, implying a role for IL-8 in the ongoing recruitment of
      neutrophils to established lesions of pneumonic pasteurellosis. Because
      neutrophil-mediated tissue injury is critical to the pathogenesis of pneumonic
      pasteurellosis, these data suggest that neutralization of IL-8 activity could
      ameliorate the severe clinical signs and lesions of this disease.

PMID- 9539365
TI  - Lethal peracute rhabdomyolysis associated with stress and general anesthesia in
      three dystrophin-deficient cats.
AB  - Three cats affected with dystrophin deficiency and hypertrophic muscular
      dystrophy developed peracute rhabdomyolysis with a fatal outcome. Two cats were
      anesthetized with isoflurane for routine procedures and did not recover properly
      from the anesthetic procedure. One cat was manually restrained for an echographic
      examination and started staggering after a short struggle; its condition
      worsened, and it died. Blood chemistry findings included severe hyperkalemia,
      hyperphosphatemia, hypocalcemia, massive increases in creatine kinase, aspartate
      aminotransferase, and alanine aminotransferase concentrations, and high ion gap
      metabolic acidosis. Light microscopic evaluation of skeletal muscle revealed
      severe acute rhabdomyolysis with marked extensive necrosis of large groups of
      fibers and endomysial edema. These lesions were observed in many skeletal muscles
      but particularly in the masseter and supraspinatus muscles and in the diaphragm.
      Typical changes associated with dystrophin deficiency in cats were also noted.
      Histochemical analysis revealed that the dystrophin deficiency was associated
      with a decrease in the percentage of type 1 myofibers in all three cats. This
      change was marked in the 20-month-old cat and milder in the younger cats (6.5 and
      8.5 months of age). Percentages of type 2A fibers were markedly decreased and
      percentages of type 2X fibers were markedly increased in the younger cats.
      Rhabdomyolysis has been reported in dystrophinopathic humans but not in other
      animal models of dystrophin deficiency. An increased sensitivity of the
      dystrophin-deficient sarcolemmal membrane to volatile anesthetic agents, stress,
      or intense muscular activity is suspected.

PMID- 9539367
TI  - Experimental Clostridium perfringens type D enterotoxemia in goats.
AB  - The effects of intraduodenal administration of Clostridium perfringens cultures
      and culture products in goats were evaluated to develop a reliable experimental
      model of enterotoxemia in this species. Five conventionally reared, 11-16-week
      old Angora goat kids were dosed intraduodenally with whole cultures of C.
      perfringens type D; five similar animals were dosed with C. perfringens type D
      filtered culture supernatant; and a third group of five kids was dosed with C.
      perfringens type D washed cells. Two kids were used as controls and received
      sterile, nontoxic culture medium intraduodenally. All animals received starch
      solution into the abomasum. All five kids inoculated with whole culture and three
      of five dosed with culture supernatant and with washed cells developed central
      nervous system signs. Diarrhea was observed in two of five kids inoculated with
      whole culture, in all five of those dosed with culture supernatant, and in three
      of five of those that received washed cells. The most striking postmortem
      findings consisted of lung edema, necrotizing pseudomembranous colitis, and
      cerebral vasogenic edema. The protocol thus provided a reasonable model of
      naturally occurring enterotoxemia in goats, producing a range of clinical signs
      and postmortem changes similar to those observed in the natural disease.

PMID- 9539368
TI  - An ovarian teratoma in a cat.
AB  - A 5-month-old, intact female, domestic shorthaired cat was presented for
      evaluation of abdominal distension. Abdominal radiographs revealed a midabdominal
      mass that contained multiple, irregular, mineralized opacities. The mass was
      surgically removed, and an ovariohysterectomy performed. The mass was located at
      the tip of the left uterine horn and was covered partially by haired skin.
      Histologically, the mass was diagnosed as a mature ovarian teratoma based on the
      presence of well-differentiated somatic structures derived from three primary
      embryonal germ-cell layers. Germ-cell tumor classification and feline ovarian
      teratomas are reviewed.

PMID- 9539370
TI  - T-cell-rich B-cell lymphoma in a pig.
AB  - A case of multicentric lymphoma with a mixed cell population of large to small
      round cells with the same nuclear features in a pig was studied
      immunohistochemically. Neoplastic tissues were composed of 20-50% B-cell lymphoma
      cells with lambda-type light chain restriction, and 50-80% cluster of
      differentiation (CD)3+ T-cells. These findings were similar to those of human T
      cell-rich B-cell lymphoma (TCRBCL). In addition, both immunoglobulin IgM and IgG
      were detected in the cytoplasm of the identical lymphoma cell. This pattern of
      heavy chain expression appeared to be due to maturational arrest in cellular
      development at the point of heavy chain class switching, as occurs in biclonal
      gammopathy in human lymphoid malignancy. This case as TCRBCL containing two types
      of heavy chains with light chain restriction (IgM-lambda and IgG-lambda) appears
      to be the first of its kind reported in the English literature for either pigs or
      domestic animals.

PMID- 9539369
TI  - Multisystemic, eosinophilic, epitheliotropic disease with intestinal
      lymphosarcoma in a horse.
AB  - Multisystemic, eosinophilic, epitheliotropic disease and intestinal lymphosarcoma
      were diagnosed in a Paso Fino mare that presented with anorexia and weight loss.
      The stomach, ileum, cecum, colon, pancreas, and lungs were infiltrated by large
      numbers of eosinophils forming prominent eosinophilic granulomas, as well as
      lymphocytes and plasma cells. Two jejunal masses composed of solid sheets of
      neoplastic lymphocytes were present. In contrast to the regions of inflammation,
      the infiltrates in these masses did not contain plasma cells, eosinophils, and
      eosinophilic granulomas. Immunohistochemically, the neoplastic lymphocytes
      expressed CD3 but not CD20 or kappa and lambda light chains, supporting a
      diagnosis of T-cell lymphosarcoma. Concurrent diagnoses of hypereosinophilic
      syndrome and lymphosarcoma in this horse and several humans suggest that the
      multisystemic eosinophilic and lymphoplasmacytic infiltrates were caused by the
      clonal proliferation of T-lymphocytes that secreted interleukin-5 triggering
      differentiation and activation of eosinophils.

PMID- 9539371
TI  - Axonal spheroids in the cochlear nucleus of normal beagle dogs.
AB  - In the course of drug evaluation studies, sporadic axonal spheroids were
      identified in the cochlear nucleus of 8-15-month-old Beagle dogs. These
      structures were identified by Bielschowski histochemical and anti-neurofilament
      immunohistochemical stains and by ultrastructural examination. No cellular
      reaction or significant neuropil alterations were associated with the presence of
      the spheroids. Their presence was unrelated to treatment and were considered to
      be an incidental background finding.

PMID- 9539373
TI  - Magnesium deficiency exacerbates brain injury and stroke mortality induced by
      alcohol: a 31P-NMR in vivo study.
AB  - Mimicking in rats the reduced level of dietary magnesium (Mg) intake, seen in
      present-day Western World populations, short-term (4 weeks) restriction of Mg
      intake (30-35% normal) resulted in a 40% loss in brain intracellular free Mg2+
      ions ([Mg2+]i) and significant rises in brain intracellular pH (pHi) and
      phosphocreatine ([PCr]) but no change in [ATP] or [Pi] as measured by 31P-NMR
      spectroscopy. Such Mg-deficient animals (serum Mg fell 65%), when given ED40
      stroke doses of ethanol, demonstrated a 100% stroke mortality. These findings
      indicate that: 1) moderate, short-term Mg deficiency makes the brain vulnerable
      to hypoxic-lethal stroke insults induced by alcohol administration, and 2) brain
      [Mg2+]i appears to play an important role in finely regulating brain pHi and
      [PCr].

PMID- 9539372
TI  - Specific detection of Lawsonia intracellularis in porcine proliferative
      enteropathy inferred from fluorescent rRNA in situ hybridization.
AB  - Fluorescent in situ hybridization targeting 16S ribosomal RNA was used for
      specific detection of the obligate intracellular bacterium Lawsonia
      intracellularis in enterocytes from pigs affected by proliferative enteropathy. A
      specific oligonucleotide probe was designed and the specificity of the probe was
      determined by simultaneous comparison with indirect immunofluorescence assay for
      detection of L. intracellularis in formalin-fixed tissue samples from 15 pigs
      affected by porcine proliferative enteropathy. We used 10 tissue samples from
      pigs without proliferative mucosal changes as negative controls. The results
      showed that the oligonucleotide probe is specific for L. intracellularis and that
      fluorescent in situ hybridization targeting ribosomal RNA is a suitable and fast
      method for specific detection and histological recognition of L. intracellularis
      in formalin-fixed tissue.

PMID- 9539374
TI  - A specific hydroxysteroid UGT is responsible for the conjugation of aliphatic
      alcohols in rats: an estimation of the importance of glucuronidation versus
      oxidation.
AB  - UDP-glucuronosyltransferase (UGT) activity for aliphatic alcohols was determined
      in microsomal liver fractions of Wistar rats. The rats were pretreated with
      inducers of cytochrome P450 and UGTs [phenobarbital (PB), beta-naphtoflavone
      (betaNF), and ethanol (10%)], and inhibition experiments with aliphatic alcohols
      and specific substrates for UGTs were performed to characterize the UGT form(s)
      responsible for the glucuronidation of aliphatic alcohols. Several UGT isoforms
      were purified from liver microsomes of low-androsterone-conjugating activity
      (LA), controls, and ethanol-pretreated rats by chromatofocusing and affinity
      chromatography. The results show aliphatic alcohols to be specific substrates for
      17beta-hydroxysteroid UGT with considerable glucuronidation rates. This
      elimination pathway for aliphatic alcohols is not inducible by the tested
      inducers. Compared with kinetic data of oxidation, glucuronidation is probably
      the main elimination pathway for alcohols with a longer chain length than C3,
      especially when oxidation pathways are inhibited by the presence of
      proportionately high ethanol concentrations.

PMID- 9539375
TI  - Role of taste and calories in the selection of ethanol by C57BL/6NHsd and Hsd:ICR
      mice.
AB  - The C57BL/6 mouse (C57) is used as a model for the human consumption of ethanol.
      Previous studies on the taste preferences of the C57 mouse indicate that ethanol
      drinking by this animal is for calories and not for a pharmacological effect. The
      purpose of this study, therefore, was to further determine the role of calories
      and taste in the selection of ethanol by the C57 mouse. C57 and outbred Hsd:ICR
      (ICR or CD-1) mice were housed two per cage with three drinking tubes. A standard
      10-day preference test of 3-30% ethanol (v/v) vs. water was performed: the mean
      maximally preferred concentrations of ethanol were 17.9% for C57 and 6.8% for ICR
      mice. Once drinking of the preferred concentration for each cage had stabilized
      at 13.2 and 0.9 g/kg/day, respectively, the third tube was filled with water,
      0.5% aspartame, isocaloric dextrose, or diluted chocolate Ultra Slim-Fast plus
      dextrose. Five days of dextrose or chocolate drink reduced the amount of ethanol
      consumed by 41% and 44% by C57 mice, but aspartame did not affect their drinking.
      Additional groups of C57 and ICR mice were habituated to a 2-h limited access to
      water. When offered a 0.5 mM quinine solution as the only fluid, both strains
      consumed the same volumes as water. Presentation of a saccharin solution was
      followed by an i.p. injection of either 0.5 M LiCl or NaCl. When given the
      saccharin solution 48 h later, the LiCl-treated mice of both strains drank less
      saccharin. The C57 mouse did not exhibit a LiCl-induced taste aversion when
      ethanol was the novel solution. As a test of response to novelty, a cork stopper
      was placed in each cage. The ICR mice gnawed much more of the cork than did the
      C57 mice. Thus, both C57 and ICR mice learned a taste aversion, but the C57 mouse
      altered its large consumption of ethanol based on more palatable sources of
      calories. These data support the earlier concept that the consumption of ethanol
      represents a preferred source of calories for the C57 mouse. Extrapolation of
      genetic or biochemical differences between these mice to differences between the
      human alcoholic and the nonalcoholic should thus be made with caution.

PMID- 9539376
TI  - Genetic selection of alcohol preference can be countered by conditioning
      processes.
AB  - Twenty-four P rats and 24 NP rats were conditioned to consume 10% w/v alcohol in
      daily 0.5-h limited access periods using a modified version of Samson's sucrose
      fading procedure. Both P and NP rats demonstrated a strikingly similar day-to-day
      pattern of alcohol intakes. For the most part, P rats drank more than NP rats,
      but by the middle of the fourth month of drinking, P and NP rats were drinking
      equivalent amounts of alcohol. Both P and NP rats consumed alcohol in amounts
      similar to two outbred strains of rats (Wistar and Sprague-Dawley) previously
      conditioned to drink alcohol in this laboratory.

PMID- 9539377
TI  - Ethanol-induced changes in hepatic chromatin and nonhistone nuclear protein
      composition in the rat.
AB  - Excessive ethanol consumption has been shown to affect hepatic nucleic acid and
      protein synthesis. This study was undertaken to identify the changes in hepatic
      chromatin and nonhistone nuclear proteins as a consequence of chronic ethanol
      treatment, because these changes could be contributory to alcoholic cirrhosis.
      Chromatin conformation was monitored by circular dichroism spectrophotometry. The
      chromatin from alcoholic rat liver showed decreased molar ellipticity (theta).
      This change in chromatin conformation influences chromatin functions such as
      replication and transcription through the regulatory pool of nonhistone nuclear
      (NHN) proteins. The NHN proteins were analysed by ultrasensitive two-dimensional
      gel electrophoresis. Specific changes in nuclear proteins were documented in the
      liver of chronic alcohol-fed rats. This study shows chronic ethanol-induced
      changes in chromatin conformation and nuclear proteins, which might be critical
      in the mechanism of alcoholic cirrhosis.

PMID- 9539378
TI  - Effects of preweanling ethanol odor exposure on ethanol preference.
AB  - Preweaning exposure to a foreign odor has been shown to alter later responding to
      that odor. Early experience with ethanol odor may alter not only responding to
      ethanol odor, but also intake of ethanol solutions. The present study tested the
      effects of exposure to ethanol odor prior to weaning on ethanol odor preference
      and ethanol consumption. Sprague-Dawley-derived rats were exposed to the odor of
      100% ethanol from postnatal day 1 to 22 in the home cage. An odor preference test
      was conducted on postnatal day 14 and a two-bottle ethanol intake test was
      conducted after weaning. In both odor preference and intake tests, animals
      previously exposed to ethanol odor exhibited a greater preference for ethanol
      than controls. The results demonstrate that early experience with the odor of
      ethanol can increase ingestion of ethanol later in life.

PMID- 9539379
TI  - Effects of neonatal ethanol exposure on cholinergic neurons of the rat medial
      septum.
AB  - The objective of this study was to determine the long-term effects of neonatal
      ethanol exposure on the cholinergic neurons in the medial septum (MS) of the rat.
      On postnatal day 4 (P4) pups were assigned to one of three groups: an ethanol
      receiving, gastrostomized group (EtOH); a pair-fed, gastrostomized control group
      (GC); and a dam-reared suckle control group (SC). Gastrostomized pups were
      infused with ethanol-containing or control diet as a 9.1% v/v solution for two
      feedings on each day from P4 to P10. Choline acetyltransferase (ChAT)
      immunocytochemistry was analyzed at P60. Ethanol treatment resulted in long
      lasting microencephaly in P60 EtOH animals. Ethanol exposure did not directly
      reduce ChAT-expressing (ChAT+) neuronal number, nor were changes noted in MS
      volume, mean area/section, or cell density as a result of ethanol treatment.
      Ethanol exposure reduced ChAT+ neuronal size in EtOH males compared with GC males
      but not SC males. No differences in ChAT+ neuronal size were noted in females.
      Thus, neonatal ethanol exposure, whereas producing long-lived microencephaly, has
      little effect on the cholinergic neurons of the adult rat MS.

PMID- 9539380
TI  - Brain opioid receptor binding of [3H]CTOP and [3H]naltrindole in alcohol
      preferring AA and alcohol-avoiding ANA rats.
AB  - We compared mu- and delta-opioid receptor distributions between the brains of
      alcohol-preferring Alko, Alcohol (AA) and alcohol-avoiding Alko, Non-Alcohol
      (ANA) rat lines, using autoradiography on brain sections with mu- and delta
      opioid receptor antagonist ligands [3H]CTOP and [3H]naltrindole, respectively.
      The labeling patterns of the ligands were consistent with the known opioid
      receptor distributions in both rat lines and no major genetic differences were
      found between the lines. However, the binding density of mu- and delta-opioid
      receptors differed slightly in several brain areas: in the AA brain sections,
      limbic areas, such as hippocampus and amygdala, showed decreased mu- and delta
      opioid receptor binding, whereas the striatal patches were larger and the
      substantia nigra showed higher binding density of the mu-receptors compared to
      the ANA sections. The small differences observed between the rat lines could be
      due to adaptations to altered endogenous opioid peptide levels or neural
      circuits, and associated with the differences in alcohol drinking or other
      behaviors.

PMID- 9539381
TI  - Chronic ethanol ingestion impairs TGF-alpha-stimulated receptor
      autophosphorylation.
AB  - The effects of chronic ethanol feeding on the binding of transforming growth
      factor-alpha (TGF-alpha) and TGF-alpha-stimulated receptor autophosphorylation
      were investigated in isolated rat hepatocytes. When hepatocytes were isolated
      from rats that were fed an ethanol liquid diet for 6-8 weeks, these cells
      exhibited a marked impairment of TGF-alpha-stimulated autophosphorylation of the
      receptor that binds this growth factor compared with hepatocytes from the pair
      fed controls. This impaired autophosphorylation of receptor tyrosine residues was
      accompanied by significant decreases in the amount of surface-bound TGF-alpha.
      Immunoanalysis indicated no changes in receptor number, indicating that decreased
      receptor content was not responsible for decreased TGF-alpha binding in the
      hepatocytes from the ethanol-fed rats. In conclusion, chronic ethanol feeding
      reduced TGF-alpha binding to hepatocytes with a concomitant decrease in the
      ability of the receptor tyrosine kinase to autophosphorylate its tyrosine
      residues. These changes were not accompanied by decreased receptor protein
      content. These defects could lead to altered signal transduction and to impaired
      reparative and regenerative processes in the liver.

PMID- 9539382
TI  - Drinking patterns in genetic low-alcohol-drinking (LAD) rats after systemic
      cyanamide and cerebral injections of THP or 6-OHDA.
AB  - A key question related to the role of acetaldehyde and aldehyde adducts in
      alcoholism concerns their relationship to the genetic mechanisms underlying
      drinking. Experimentally, the low-alcohol-drinking (LAD) rat represents a
      standard rodent model having a strong aversion to alcohol. In these experiments,
      preferences for water vs. alcohol, offered in concentrations from 3% to 30%, were
      determined over 10 days in adult LAD rats (N = 6 per group). Then a saline
      vehicle or either 10 or 20 mg/kg of the aldehyde dehydrogenase (AIDH) inhibitor,
      cyanamide, was injected s.c. twice daily for 3 days. Secondly, either 0.5 or 1.0
      microg of tetrahydropapaveroline (THP) was infused i.c.v. twice daily for 3 days
      in LAD rats (N = 8) and, as a genetic control, THP also was infused identically
      in Sprague-Dawley (SD) rats (N = 8). The results showed that the lower and higher
      doses of cyanamide augmented alcohol intakes in 33% and 50% of the LAD rats,
      respectively, with the patterns of drinking resembling that of genetic high
      alcohol-drinking HAD or P rats. Although i.c.v. infusions of THP had little
      effect on alcohol preference of LAD rats, alcohol drinking was enhanced
      significantly in the SD rats. In a supplementary study, 200 microg of 6
      hydroxydopamine (6-OHDA) also was infused i.c.v. in LAD rats (N = 7) on two
      consecutive days; no change occurred in the characteristic aversion to alcohol.
      These findings suggest that in certain individuals, a perturbation in the
      synthesis of AIDH can modify the genetically based aversion to alcohol, thus
      precipitating the liability for alcoholism. In that neither THP nor 6-OHDA
      lesioning exerted any effect on the genetic nondrinking LAD animal suggests that
      an unknown endogenous factor in the brain must underlie the cyanamide-induced
      shift to alcohol preference. We conclude that the genetic elements that normally
      prevent the progression to addictive drinking in most individuals appear to be
      invariant and irreversible.

PMID- 9539383
TI  - Biological water and its role in the effects of alcohol.
AB  - Alcohol and water compete with each other on target membrane molecules,
      specifically, lipids and proteins near the membrane surface. The basis for this
      competition is the hydrogen bonding capability of both compounds. But alcohol's
      amphiphilic properties give it the capability to be attracted simultaneously to
      both hydrophobic and hydrophilic targets. Thus, alcohol could bind certain
      targets preferentially and displace water, leading to conformational
      consequences. This article reviews the clustering and organized character of
      biological water, which modulates the conformation of membrane surface molecules,
      particularly receptor protein. Any alcohol-induced displacement of biological
      water on or inside of membrane proteins creates the opportunity for allosteric
      change in membrane receptors. This interaction may also prevail in organelles,
      such as the Golgi apparatus, which have relatively low concentrations of bulk
      water. Target molecules of particular interest in neuronal membrane are
      zwitteronic phospholipids, gangliosides, and membrane proteins, including
      glycoproteins. FTIR and NMR spectroscopic evidence from model membrane systems
      shows that alcohol has a nonstereospecific binding capability for membrane
      surface molecules and that such binding occurs at sites that are otherwise
      occupied by hydrogen-bonded water. The significance of these effects seems to lie
      in the need to learn more about biological water as an active participant in
      biochemical actions. Proposed herein is a new working hypothesis that the
      molecular targets of ethanol action most deserving of study are those where water
      is trapped and there is little bulk water. Proteins (enzymes and receptors)
      certainly differ in this regard, as do organelles.

PMID- 9539384
TI  - Timing of early changes in brain trauma.
AB  - One hundred and fourteen fatal cases of brain trauma were examined prospectively;
      in 100 of these cases, death occurred within 48 hours of injury. The methods of
      injury included motor vehicle accidents (MVA), gunshot wounds, blunt instrument
      injuries, and falls. All cases showed subarachnoid and parenchymal hemorrhages.
      Paraffin sections were studied with hematoxylin and eosin (H&E) stain and also
      with special stains in selected slides. The cases were examined histologically
      before having exact clinical knowledge of the time of death. Eosinophilic neurons
      were noted in many cases surviving <1 hour after injury and increased in
      frequency and severity with time. These were most commonly seen in areas of
      contusion, the hippocampus, and the arterial boundary zones of the cerebral
      cortex. Neuronal incrustation was seen from 3 to 48 hours postinjury in areas of
      contusion. Axonal swelling and spheroids were seen in the white matter in areas
      of laceration and hemorrhage at 1 hour postinjury in many cases and continuing
      through all time periods. Glial swelling was seen in the subpial and subependymal
      regions and around hemorrhages from very early to 48 hours postinjury.
      Polymorphonuclear leukocytes (granulocytes) were present in the tissues at all
      time periods with increasing frequency over time. They were also found
      surrounding corpora amylacea in cases with <1 hour survival. Axonal swelling,
      eosinophilia of neurons, and incrustation of neurons were noted at earlier time
      periods than previously reported in the literature. Determining the time of
      injury based on histologic evidence is difficult. We believe that the data
      reported here will allow more accurate appreciation of timing of the early
      interval between brain trauma and death.

PMID- 9539385
TI  - Forensic applications of DNA typing: part 2: collection and preservation of DNA
      evidence.
AB  - The initial stages of physical evidence examination are pivotal to the successful
      resolution of criminal investigations. Recent cases clearly reinforce the notion
      that methods of evidence collection and preservation will continue to be
      rigorously scrutinized and challenged in court. This article reviews forensic
      applications of DNA typing, focusing on the collection and preservation of
      biological evidence. Topics addressed include physical evidence collection at the
      crime scene, the forensic laboratory, and the autopsy room. Specific concerns
      pertaining to different sources of DNA evidence are discussed, as are special
      collection methods associated with various substrates on which the evidence is
      deposited.

PMID- 9539386
TI  - Fatal hypernatremic dehydration in exclusively breast-fed newborn infants due to
      maternal lactation failure.
AB  - Infants who die of hypernatremic dehydration usually demonstrate at autopsy an
      underlying condition or disease process that predisposes to increased water loss.
      In the absence of such findings, forensic concerns may focus sharply on parental
      or caretaker neglect as an underlying cause of death. In this case report, we
      describe unrecognized fatal hypernatremic dehydration in two exclusively breast
      fed neonates due solely to failure of maternal lactation. We further describe
      epidemiologic and etiologic features of such deaths and discuss forensic
      difficulties encountered in their certification.

PMID- 9539387
TI  - Three unusual cases of multiple suicidal gunshot wounds to the head.
AB  - We describe three unusual cases of suicide involving multiple gunshot wounds, in
      which all of the victims suffered gunshot wounds to the head, yet none was
      rendered immediately incapacitated. Injuries were confined to the same area in
      two of the cases and were located in different areas in the other case. Two of
      the cases initially appeared to be homicides rather than suicides.

PMID- 9539388
TI  - Multiple entrance wounds from one bullet due to the use of a silencer.
AB  - When a bullet strikes an interposed object before entering a body, the bullet may
      fragment, or particles from the interposed object may be accelerated. Such
      secondary missiles may cause multiple entrance wounds if a body is located in
      line with their flight path. In the unusual case reported here, a silencer acted
      as an interposed object. The bullet disintegrated completely after impact with
      the central part of the silencer baffles, which were misaligned. Some bullet
      fragments were retained inside the silencer, and some exited as a collection of
      missiles, comparable to shotgun pellets. From a distance of several meters, the
      fragments wounded the victim at seven different anatomic sites. Use of a silencer
      should be considered when bullet fragments are recovered from a scene or victim
      but no other appropriate interposed object is found.

PMID- 9539389
TI  - Violent mass shootings in Sweden from 1960 to 1995: profiles, patterns, and
      motives.
AB  - During the past few decades, violent mass shooting in Sweden has increased
      rapidly. In the 36 years between 1960 and 1995, fourteen such occasions were
      recorded, during which 32 people were killed and 57 were wounded. The 14
      offenders were men between the ages of 17 and 61 years. In the 20 years from 1960
      to 1979, five shootings were committed by five offenders, leaving 10 dead and 13
      wounded; in the 16 years between 1980 and 1995, there were nine different
      shootings committed by nine offenders, with 22 dead and 44 wounded. Seven of the
      shootings were classified as mass shootings, six as spree shootings, and one as a
      serial shooting. In all but four of these cases, the firearms used were illegal
      weapons. The four legal firearms belonged to an unemployed young laborer, an
      officer, a former United Nations (U.N.) soldier, and a member of the Swedish
      military volunteer corps. Of those killed, 68.8% were strangers to the offender;
      among the wounded, the corresponding figure was 89.5%. Profiles of the offenders
      and of the victims were studied. The psychiatric diagnoses among the offenders
      and the measures taken to prevent the increase in mass shooting in Sweden are
      presented.

PMID- 9539390
TI  - Postmortem extravasation of blood potentially simulating antemortem bruising.
AB  - A case of florid postmortem extravasation of blood, potentially simulating
      antemortem bruising, is presented. A 98-year-old woman died in hospital, the
      cause of death being certified as congestive cardiac failure. After burial, it
      was apparent that the grave had been disturbed by crowbars and shovels.
      Exhumation was performed and autopsy revealed considerable apparent facial
      bruising as well as lacerations and fractures. There was no documentation by the
      medical or nursing staff of any injuries to the deceased preceding death. There
      was also no documentation of injury by the funeral directors. Subsequently, two
      men admitted to removing the body from the grave and mutilating it. Thus, what
      was apparently facial bruising was, in fact, postmortem extravasation of blood
      simulating antemortem bruising. The degree of extravasation was considered to be
      related to the severity of the injuries, loose subcutaneous tissues of the head
      and neck, and dependent position of the body upon return to the grave. This case
      demonstrates the degree of postmortem extravasation of blood that may occur in
      particular circumstances and may simulate antemortem bruising. In other
      circumstances, the postmortem extravasation of blood may well have led
      investigators to pursue inquiries regarding homicide.

PMID- 9539391
TI  - Is flow cytometric evaluation of DNA degradation a reliable method to investigate
      the early postmortem period?
AB  - The time of death can be established by determining the length of the postmortem
      interval. Many methods have been proposed to achieve this goal. Flow cytometric
      evaluation of DNA degradation seems to be reliable for the first 72 hours after
      death. Our study evaluated the correspondence of the corruption process between
      in vitro and corpse tissues. We chose spleen tissue to perform our investigation
      because it is rich in nucleated cells. Results showed a precise correspondence
      between the two kinds of samples in the time period between 24 and 36 hours. The
      period from 36 to 72 hours is characterized by a much looser correspondence than
      that found in the first period. After the first 72 hours, DNA denaturation is
      massive and does not allow useful cytofluorimetric readings. The spleen does not
      seem to be the most suitable organ for this type of investigation because it
      tends to colliquate very rapidly. We therefore are evaluating other organs to
      identify a more suitable tissue source for the investigation of longer postmortem
      period using flow cytometry.

PMID- 9539392
TI  - Suggested guidelines for platform presentations.
AB  - A platform presentation at an academic meeting requires preparation, practice,
      and self-discipline. Our observations and discussions of presentations made at
      national meetings of forensic scientists over the past several years compelled us
      to review the essentials of public speaking in the academic arena. We translated
      this review into a compilation of recommendations for the prospective presenter.
      Application of these recommendations will result in more informative, efficient,
      and enjoyable platform presentations.

PMID- 9539393
TI  - Child abuse reports in families with sudden infant death syndrome.
AB  - This study investigates the relation between sudden infant death syndrome (SIDS)
      cases and reports to public child protection service (CPS) agencies of suspected
      child abuse or neglect prior to the sudden deaths. SIDS data were collected from
      the Ventura County Medical Examiner's death investigation records of 1981 through
      1995. Names of deceased infants, their parents, and any other caretakers who
      might have been with the infant near the time of death were submitted to the
      county CPS, where they were referenced for reports of abuse or neglect. A control
      population of non-SIDS infants and their caretakers were checked in a similar
      manner. The 150 infants from the control group were compared with 157 SIDS
      infants; no significant statistical difference was found between groups in the
      incidence or type of CPS referrals. These findings suggest that screening CPS
      records for previous referrals is an ineffective method by which to detect
      infanticides misdiagnosed as SIDS and may cast unwarranted suspicion on otherwise
      typical SIDS cases.

PMID- 9539395
TI  - Follow-up on the Berg acid phosphatase test.
AB  - Approximately 42 years ago, the Berg acid phosphatase (AP) test (1) was accepted
      in most rape treatment centers nationally as the standard to determine whether
      sexual intercourse or related actions in any form had occurred. More
      specifically, the test was designed to determine the presence of a certain
      enzyme. In October 1969, I published an article making the test simpler (2) and
      reviewing the history of various tests for the detection of AP, an enzyme found
      in great abundance in seminal fluid. Both AP-impregnated material and
      refrigerated reagents had been saved along with a quantity of seminal fluid used
      in the original tests. The objectives of this study were to determine whether 25
      year-old seminal fluid in any form can still be identified by the AP test and
      whether 25-year-old chemicals have remained stable and are still usable.

PMID- 9539394
TI  - Suicide bombers in Israel.
AB  - Between 1993 and 1995, 14 suicidal terrorist bombings took place in Israel; 86
      victims perished in these attacks, which were carried out by militant Palestinian
      organizations that oppose peace treaties between the state of Israel and the
      Palestinian people. The modus operandi of the perpetrators was detonating, in a
      public area, an explosive device carried on or in close proximity to the
      terrorist's body. We reviewed the postmortem examinations and identification
      procedures performed by the medical and law enforcement personnel involved in
      mass disaster management. The types of injuries sustained by the victims and
      perpetrators include body disruption, explosive injuries, flying missile
      injuries, and blast injuries. Blunt trauma directly produced by the explosion and
      flying missile injuries account for 80.1% of the wounds. The number of fatalities
      was more closely related to the type of the attack rather than to the amount and
      type of explosives used. Swift identification of all victims and perpetrators was
      obtained through collaboration between the different professional teams involved:
      forensic scientists, law enforcement agencies, and secret service investigators.
      Based on the analysis of the data obtained from the necroscopic examinations, we
      observed that most of the wounds sustained fall within the realm of blunt force
      injuries; emergency medical facilities that might be faced with similar
      situations should prepare accordingly. Collaboration between the various forensic
      and law enforcement teams results in swift resolution of disaster management.
      Prompt identification of the perpetrators allows the authorities to apprehend any
      accomplices and to prevent similar attacks.

PMID- 9539396
TI  - Sudden death due to undetected mediastinal germ cell tumor.
AB  - A 32-year old man, apparently asymptomatic, was found dead in his apartment.
      Autopsy revealed a large necrotic mediastinal mass with liver and occipital brain
      metastases, the latter having produced acute intraparenchymal and
      intraventricular hemorrhage with cerebellar tonsillar herniation. Histologically,
      the mediastinal mass and metastases were consistent with immature extragonadal
      teratoma, with malignant transformation of the intestinal-type epithelium.
      Undiagnosed neoplasms as causes of sudden death are quite rare and usually
      reported in older age groups; however, in one study of autopsies in a 25-to 46
      year-old age group, a significant 3.2% was reported. Germ cell tumors of the
      mediastinum are the most common extragonadal primary site, accounting for
      approximately 50%-70% of extragonadal germ cell tumors (EGCTs) and primarily
      affecting 20- to 35-year-old men. EGCTs are usually symptomatic at the time of
      diagnosis, although a large proportion may be asymptomatic. This case represents
      one the few reported cases of sudden death as a result of mediastinal EGCT; it
      also demonstrates the natural course of this disease and underscores the
      importance of medicolegal autopsies in cases of sudden death.

PMID- 9539397
TI  - Weight of adrenal glands may be increased in persons who commit suicide.
AB  - In a previous study, increased weight of the adrenal glands was found in a small
      group of persons who committed violent suicides. This finding was confirmed in
      our study, which comprised a group of 42 suicide cases and 37 control cases.
      Further analysis with special consideration toward a "relative adrenal weight"
      (weight/body surface) revealed that a relative combined adrenal weight >6 g/m2
      may be a morphologic sign of a depressive disorder prior to death if no other
      disease with a known effect on the adrenals is present. These results are
      consistent with clinical computed tomographic findings of enlarged adrenals in
      depressed patients. In all suicide cases the police records were reviewed and a
      postmortem psychiatric diagnosis conducted to investigate whether a correlation
      between adrenal weight and the "severity" of depression or type of psychiatric
      disorder exists. In thirteen cases, psychiatric treatment prior to death was
      known, and a postmortem severity score of depressive disease was formed. No
      influence of this score or the postmortem diagnosis on the adrenal weight,
      however, could be detected. Also, the increase in weight of adrenal glands could
      not be explained by a suspected or proven preceding drug therapy or use. The
      effect on the pituitary-adrenal-axis by depressive disorders and changes in
      serotonin metabolism have been investigated repeatedly; mainly reported are
      increased levels of corticotropin-releasing hormone (CRH) and adrenocorticotropic
      hormone (ACTH) in the depressive interval, which may lead to a growth of the
      adrenal glands.

PMID- 9539398
TI  - Improvement of age estimation using amino acid racemization in a case of pink
      teeth.
AB  - Age was estimated from pink teeth using racemization of dentinal aspartic acid.
      Materials for identification were two lower second premolars. The body was
      determined to be that of a 40-year-old man; however, the age of the decedent had
      been estimated to be 29 and 30 years by the conventional method and 30 years from
      findings in the oral cavity. To clarify the cause of this difference, the
      powdered teeth were further washed in 0.01 mol/L hydrochloric acid. The
      racemization ratio (D/L ratio) of ordinary white teeth from persons of known age
      was slightly lower than that before washing, whereas that of the teeth used for
      identification was higher than before washing. The calculated age of the decedent
      using the racemization ratio of his teeth was between 36 and 37 years. These
      results suggest that age estimated from pink teeth is probably underestimated,
      but a more accurate age estimate can be obtained after adequate washing.

PMID- 9539399
TI  - Interpretation of accelerants in blood of cadavers found in the wreckage after
      fire.
AB  - Accelerants in the blood of 73 cadavers found in wreckage after fire were
      analyzed by gas chromatography (GC) and a combination of gas chromatography-mass
      spectrometry (GC-MS) to decide whether accelerants containing petroleum
      components had been used and whether the cadavers had been exposed to fire before
      or after death. In 16 of 26 cases in which accelerants were used to start a fire
      before death, accelerants were detected in the blood. In 7 cases in which
      accelerants were used to start a fire, the victims were determined to have been
      exposed to the vapor of accelerants after death because no accelerants were
      detected in the blood, no soot was found in the airways, and carboxyhemoglobin
      (COHb) concentrations were not higher than those found in smokers. In 9 of 34
      cases in which accelerants were suspected to have been used to start a fire
      before death, accelerants were detected in the blood. When soot is not detectable
      by the unaided eye in the airways of a victim found in debris of a fire in which
      the use of accelerants is suspected, or the COHb concentration in the blood is no
      higher than in a smoker, analysis of accelerants in the blood seems to be helpful
      in determining the cause of death and whether inflammable were used.

PMID- 9539400
TI  - Typical homicide ritual of the Italian Mafia (incaprettamento)
AB  - Certain methods of homicide used by the Italian Mafia are intended to have an
      admonitory significance. One such method is the so-called "incaprettamento." This
      study analyzes 18 cases of homicidal ligature strangulation in which the body was
      found in this typical position. The circumstances of the crime and the
      macroscopic and microscopic evidence were evaluated to determine whether or not
      the ligatures on the wrists and ankles were placed antemortem or postmortem.

PMID- 9539401
TI  - Streptococcal toxic shock syndrome presenting as suspected child abuse.
AB  - Natural disease processes can predispose individuals to develop external body
      lesions that mimic traumatic injury. This can be particularly problematic in
      pediatric cases in which clinicians are alerted to the problems of child abuse.
      Streptococcal toxic shock syndrome is a systemic infectious illness that can
      manifest itself with erythematous and necrotizing skin lesions. We report a fatal
      case of streptococcal toxic shock syndrome in a 4-year-old girl who presented
      with skin lesions that were initially thought to be traumatic in origin. A report
      of possible child abuse was filed with the state. Based on the morphologic
      findings and bacteriologic culture results at autopsy, these lesions and the
      cause of death in this case were instead determined to result from streptococcal
      toxic shock syndrome.

PMID- 9539402
TI  - Diabetes and decomposition: a case of diabetic ketoacidosis with advanced
      postmortem change.
AB  - The case is presented of a 34-year-old man, an insulin-dependent diabetic, who
      was found decomposed in his apartment. The victim had been recently discharged
      from a mental hospital and was to be monitored by the community's mental health
      personnel. While the autopsy revealed little in the way of disease, toxicological
      studies yielded a blood acetone level of 0.070 g/dl and a urine acetone level of
      0.086 g/dl. The medical examiner ruled the cause of death diabetic ketoacidosis.
      To support this conclusion in the absence of a vitreous humor glucose
      concentration, 18 well-documented cases of diabetic ketoacidosis were reviewed,
      and acetone concentrations were compared with the acetone concentrations found in
      the presented case.

PMID- 9539403
TI  - Suicide using a compound bow and arrow.
AB  - Accidental, suicidal, and homicidal injuries have been caused by arrows fired
      from crossbows. To our knowledge, a case of suicide using a full-size compound
      bow to fire a projectile has not been reported in the English literature.
      Described is a case of a 17-year-old man who shot himself in the chest with a
      broadhead hunting arrow fired from a compound bow. Examination of the footwear
      suggests that the decedent drew the bowstring with his left foot while holding
      the bow in his hands. The mechanism of injury is discussed. When dealing with a
      longbow-related fatality, examination of the weaponry used and reenactment of the
      fatal methodology are critical in determining whether self-inflicted injury is a
      probability.

PMID- 9539404
TI  - Screening for cognitive impairment in general practice: toward a consensus.
AB  - We considered whether general practitioners should examine all older patients
      over a certain age for cognitive impairment in screening for early dementia. We
      invited presentations from key experts, selectively reviewed the literature, and
      developed a consensus statement. The efficacy of and benefits from unselective
      use of cognitive testing and informant questionnaires for detecting early
      dementia in older patients attending general practice are limited. Positive
      predictive values of cognitive screening for dementia are less than 50%, even for
      older patient populations. Higher values may be obtained by testing patients who
      have a relevant history of cognitive or functional decline. Whatever procedures
      are adopted for screening older general practice attenders for cognitive
      impairment or early dementia, investigation is still required into the relative
      merits of different health professionals performing the screening, the positive
      and negative effects on patients and their families, and the cost-benefit ratio.
      The majority view of workshop participants was that cognitive testing should
      occur for older patients when there is a reason to suspect dementia. Testing may
      occur in an individual considered to be at risk because of an informant history
      of cognitive or functional decline, clinical observation, or, sometimes, very old
      age. No single instrument for cognitive screening is suitable for global use.
      Screening programs must be supported by training and supplemented by education
      for professionals and families in management of dementia.

PMID- 9539405
TI  - Benzodiazepines may have protective effects against Alzheimer disease.
AB  - In this study, we examined the association between benzodiazepine use and the
      occurrence of Alzheimer disease and vascular dementia. The study was based on
      longitudinal data from a case-control study of 668 individuals aged 75 and older.
      The elderly were examined extensively by physicians, and family interviews were
      assessed. Dementia diagnosis was made by using DSM-III-R criteria. Individuals
      with a history of continuous use of benzodiazepines (BDZ+) were compared with
      nonusers (BDZ-), with respect to the incidence of Alzheimer disease or vascular
      dementia at follow-up 3 years later. It was found that there was a significantly
      lower incidence of Alzheimer disease in the BDZ+ group than in the BDZ- group.
      This negative association remained significant when controlling for age, gender,
      level of education, use of nonsteriodal antiinflammatory drugs, and estrogens.
      These results suggest that benzodiazepines may have protective effects against
      the disease.

PMID- 9539406
TI  - Effects of familiarity and temporal organization on memory for event schemas in
      aged and Alzheimer subjects: implications for clinical management.
AB  - Individuals with Alzheimer disease (AD) often forget how to perform everyday
      activities. To understand better this type of memory loss, the effects of
      familiarity and temporal organization on memory for event schemas was
      investigated in college students, elderly controls, and individuals with AD.
      Participants were asked to read short stories describing common activities. Both
      recall and recognition memory were assessed immediately after reading the story.
      The number of items correctly remembered and the error types were recorded and
      analyzed. Both familiarity and temporal organization were found to play a role in
      memory for event schemas. All groups remembered the most information when the
      stories were familiar and sequentially organized. Elderly participants were more
      likely to remember items associated with, but included in, the stories than were
      the other groups. The AD group was the only group to recall or recognize items
      not associated with the story. It was concluded that event schema memory in AD
      participants is moderated by the same factors that influence memory in healthy
      young and elderly participants. These results suggest that individuals with AD
      will be best able to perform common everyday activities when they are familiar
      and when daily activities follow a predictable sequential pattern.

PMID- 9539407
TI  - Superoxide dismutase activity in cerebrospinal fluid of patients with dementia
      and some other neurological disorders.
AB  - Data on superoxide dismutase (SOD) activity in the cerebrospinal fluid (CSF) of
      patients suffering from dementia (n=32) as compared with a control group (n=58),
      a Parkinson disease (PD) patient group (n=12), and a group of individuals
      suffering from epilepsy (n=13) are presented. SOD activity was determined by
      electron spin resonance spectrometry using the spin trap method. No significant
      correlation was found between CSF SOD activity and age in the control group. In
      addition, CSF SOD activity was not gender dependent. One-way analysis of variance
      showed a highly significant between-groups effect for the CSF SOD activity and
      specific CSF SOD activity of the four major groups (p=0.0008). Post hoc
      comparison (Fisher PLSD test) revealed significant differences between the
      control group and the total dementia group (p < 0.001), between the dementia
      group and the epilepsy group (p < 0.01), and between the dementia group and the
      PD group (p < 0.05). The CSF of patients with PD or epilepsy showed a similar SOD
      activity as the CSF of control patients. In addition, CSF SOD activity levels
      were significantly lower in the total dementia group (p=0.002) and in the group
      with dementia of the Alzheimer type (DAT) (p=0.001) than in the dementia age
      matched control group. No significant difference was found for CSF SOD activity
      levels between the control group and the non-DAT dementia group. This result
      corresponded with a reduction of CSF SOD activity in the total dementia group,
      DAT subgroup, and non-DAT subgroup of 37, 43, and 22%, respectively. No
      significant correlation between the Mini-Mental State Examination score and CSF
      SOD activity was found in DAT. The lowered CSF SOD activity in Alzheimer disease,
      as demonstrated here, may reflect impaired radical defense mechanisms and may
      have possible pathophysiological significance.

PMID- 9539408
TI  - Apolipoprotein E4 promotes incipient Alzheimer pathology in the elderly.
AB  - To evaluate the influence of the apolipoprotein E (ApoE) epsilon4 allele on the
      age at which Alzheimer-like lesions appear in the brain, we analyzed the degree
      of cerebral beta-amyloidosis and neurofibrillary tangle formation in the
      hippocampal formation and adjacent cortical areas 28, 27, and 36 of persons who
      had died between the ages of 50 and 93 years and who had shown no signs of
      clinical dementia. The occurrence of the three common polymorphisms of the ApoE
      gene in this sample of 147 routine autopsy cases from eastern Germany was
      comparable to previously reported values in European and North American
      populations: ApoEepsilon2/2, 0.7%; ApoEepsilon2/3, 14.3%; ApoEepsilon2/4, 4.1%;
      ApoEepsilon3/3, 56.5%; ApoEepsilon3/4, 22.4%; and ApoEepsilon4/4, 2.0%.
      Nondemented persons carrying the ApoEepsilon4 allele were significantly more
      likely to have senile plaques, diffuse amyloid deposits, cerebrovascular amyloid,
      and neurofibrillary tangles than were those lacking E4. Comparing the two largest
      ApoE subgroups, ApoEepsilon3/3 and ApoEepsilon3/4, the relative increase in the
      occurrence of beta-amyloid in the epsilon3/4 group was evident by the mid-60s,
      with the relative increase in neurofibrillary tangles in this group emerging
      slightly earlier. The ApoEepsilon2 allele appears to delay the appearance of the
      lesions somewhat. We conclude that ApoEepsilon4 promotes the early appearance of
      beta-amyloid and neurofibrillary tangles in the elderly and that the increased
      frequency of these lesions is related to the higher risk of Alzheimer disease in
      persons bearing the ApoEepsilon4 allele.

PMID- 9539409
TI  - Risk of Alzheimer disease with the epsilon4 allele for apolipoprotein E in a
      population-based study of men aged 62-73 years.
AB  - The epsilon4 allele at APOE, the polymorphic locus for apolipoprotein E,
      increases the risk of Alzheimer disease (AD), especially among those with the
      homozygous epsilon4/epsilon4 genotype. In family studies, epsilon4 homozygotes
      typically develop AD at 55-75 years, an age range when AD is otherwise relatively
      infrequent. Population-based studies of the AD risk associated with allele
      epsilon4 (and especially with genotype epsilon4/epsilon4) are limited in number,
      and most such studies have included few AD cases between the ages of 55 and 75
      years. In a large population-based twin registry, the screening of 12,709 men who
      were 62-73 years old yielded 38 prevalent cases of AD whose onset age ranged from
      54 to 73. Genotype at APOE was determined for 37 of these cases and
      independently, for a similarly aged probability sample of 344 men from the same
      registry. The epsilon4 allele frequencies among the AD cases and the population
      samples were 0.39 and 0.15, respectively. The odds ratios (ORs) for AD were 17.7
      for genotype epsilon4/epsilon4 versus epsilon3/epsilon3 and 13.8 for
      epsilon4/epsilon4 versus all remaining genotypes. By contrast, the ORs with
      heterozygous epsilon4/epsilon3 were only 2.76 versus epsilon3/epsilon3 and 2.01
      versus all genotypes other than epsilon4/epsilon3 (p for homozygote vs.
      heterozygote ORs=0.002). The estimated etiologic fraction for AD with homozygous
      epsilon4 among men in their mid-50s to mid 70s is therefore 0.20; for the much
      more common heterozygous genotype epsilon4/epsilon3, the fraction is 0.18. In
      combination with other studies that have adjusted statistically for age, these
      results suggest that the effect of the epsilon4 allele dose is neither linear nor
      homogeneous for age. Homozygous epsilon4/epsilon4 appears to confer an extreme
      risk of AD at the age when onset with this genotype is most likely. These results
      are consistent with the view that individual genotypes modify risk by
      predisposing to substantially different distributions of AD onsets.

PMID- 9539410
TI  - Apolipoprotein E4 in Parkinson disease and dementia: new data and meta-analysis
      of published studies.
AB  - The authors examined whether the epsilon4 allele might be associated with
      dementia in Parkinson disease (PD), given that the dementia of PD shares
      neuroanatomic and neurochemical features with Alzheimer disease (AD) and that
      many recent studies have found a high prevalence of the epsilon4 allele of
      apolipoprotein E (ApoE) in AD. The authors examined patients with PD (n=125, 47
      demented) and unrelated controls (n=93) using a short mental test. DNA was
      obtained from blood leukocytes. The relevant portion of the apolipoprotein E
      (ApoE) gene was amplified by polymerase chain reaction, and the epsilon4 allele
      was identified using a restriction enzyme. The frequency of the ApoE epsilon4
      allele in demented patients with PD (14%) was not greater than that in
      nondemented patients (17%), whereas patients with PD as a whole showed a trend
      toward a higher epsilon4 allele frequency (16%) than age-matched controls (10%,
      p=0.07). The epsilon4 allele frequency in nondemented patients with PD was
      significantly higher than in controls (p=0.055). These results and the meta
      analysis of four published reports fail to support the hypothesis that the
      epsilon4 allele is associated with dementia in PD.

PMID- 9539411
TI  - Brain volumes and regional cerebral blood flow in carriers of the Swedish
      Alzheimer amyloid protein mutation.
AB  - As a preliminary part of a longitudinal clinical study of carriers of the Swedish
      amyloid precursor protein (APP) 670/671 mutation, 13 members of a family were
      investigated with magnetic resonance imaging (MRI) brain volumetry and single
      photon emission computed tomography (SPECT) cerebral blood flow (CBF)
      measurements. Five of the family members were mutation carriers; eight were not
      carriers. Two carriers were younger than 40 years of age and had no evidence of
      cognitive dysfunction or structural or functional brain changes. One carrier with
      4 years to expected disease onset showed poor performance in episodic memory
      tests and also slightly low temporal lobe CBF, although there were no clearly
      abnormal findings. One carrier with mild Alzheimer disease (AD) had no clear
      structural brain changes, although CBF measurements showed clear reduction of
      temporal lobe CBF. One carrier with severe AD had both temporal lobe atrophy and
      CBF reduction. This indicates that in carriers of the APP 670/671 mutation,
      reduction of regional CBF is more severe than regional atrophy. The clearest
      change related to development of clinical AD was a reduction of CBF in the basal
      and lateral temporal lobes. Further longitudinal studies of these subjects are
      needed to confirm these preliminary findings, which might provide important data
      regarding early brain changes in AD.

PMID- 9539412
TI  - Effects of metrifonate on cognitive decline in Alzheimer disease: a double-blind,
      placebo-controlled, 6-month study.
AB  - Forty-seven patients with probable Alzheimer disease (AD) completed a 6-month
      double-blind study to compare metrifonate with placebo. The Alzheimer Disease
      Assessment Scale cognitive subscale score of the metrifonate group treated to a
      50-70% inhibition of red blood cell acetylcholinesterase activity differed
      significantly from the placebo group score by 1.8 points (p < 0.03) due to a
      deterioration in cognitive performance in the placebo group (p < 0.01).
      Statistically significant deterioration also occurred in the Mini-Mental State
      Examination scores (p < 0.01) in the placebo-treated group. Adverse effects were
      uncommon and did not require adjustment of the dose of metrifonate or
      discontinuation of treatment. These findings extend our previous report of a
      favorable effect of metrifonate on cognitive symptoms in AD by showing clinical,
      not only statistical, significance.

PMID- 9539413
TI  - 90 years ago: the beginning of hybrid maize.

PMID- 9539414
TI  - Likelihood models for detecting positively selected amino acid sites and
      applications to the HIV-1 envelope gene.
AB  - Several codon-based models for the evolution of protein-coding DNA sequences are
      developed that account for varying selection intensity among amino acid sites.
      The "neutral model" assumes two categories of sites at which amino acid
      replacements are either neutral or deleterious. The "positive-selection model"
      assumes an additional category of positively selected sites at which
      nonsynonymous substitutions occur at a higher rate than synonymous ones. This
      model is also used to identify target sites for positive selection. The models
      are applied to a data set of the V3 region of the HIV-1 envelope gene, sequenced
      at different years after the infection of one patient. The results provide strong
      support for variable selection intensity among amino acid sites The neutral model
      is rejected in favor of the positive-selection model, indicating the operation of
      positive selection in the region. Positively selected sites are found in both the
      V3 region and the flanking regions.

PMID- 9539415
TI  - The involvement of cellular recombination and repair genes in RNA-mediated
      recombination in Saccharomyces cerevisiae.
AB  - We previously demonstrated that a reverse transcript of a cellular reporter gene
      (his3-AI) can serve as the donor for gene conversion of a chromosomal his3
      deltaMscI target sequence, and that this process requires the yeast recombination
      gene RAD52. In this study, we examine the involvement of other recombination and
      repair genes in RNA-mediated recombination, and gain insight into the nature of
      the recombination intermediate. We find that mutation of the mitotic RecA
      homologs RAD51, RAD55, and RAD57 increases the rate of RNA-mediated recombination
      relative to the wild type, and that these gene functions are not required for RNA
      mediated gene conversion. Interestingly, RAD1 is required for RNA-mediated gene
      conversion of chromosomal his3-deltaMscI sequences, suggesting that the cDNA
      intermediate has a region of nonhomology that must be removed during
      recombination with target sequences. The observation that both RAD1 and RAD52 are
      required for RNA-mediated gene conversion of chromosomal but not plasmid
      sequences indicates a clear difference between these two pathways of homologous
      RNA-mediated recombination.

PMID- 9539416
TI  - Substitutions in the pheromone-responsive Gbeta protein of Saccharomyces
      cerevisiae confer a defect in recovery from pheromone treatment.
AB  - The pheromone-responsive Galpha protein of Saccharomyces cerevisiae, Gpa1p,
      stimulates an adaptive mechanism that downregulates the mating signal. In a
      genetic screen designed to identify signaling elements required for Gpa1p
      mediated adaptation, a large collection of adaptive-defective (Adp-) mutants were
      recovered. Of the 49 mutants characterized thus far, approximately three-quarters
      exhibit a dominant defect in the negative regulation of the pheromone response.
      Eight of the dominant Adp- mutations showed tight linkage to the gene encoding
      the pheromone-responsive Gbeta, STE4. Sequence analysis of the STE4 locus in the
      relevant mutant strains revealed seven novel STE4 alleles, each of which was
      shown to disrupt proper regulation of the pheromone response. Although the STE4
      mutations had only minor effects on basal mating pathway activity, the mutant
      forms of Gbeta dramatically affected the ability of the cell to turn off the
      mating response after exposure to pheromone. Moreover, the signaling activity of
      the aberrant Gbetagamma subunits was suppressed by G322E, a mutant form of Gpa1p
      that blocks the pheromone response by sequestering Gbetagamma, but not by E364K,
      a hyperadaptive form of Gpa1p. On the basis of these observations, we propose
      that Gpa1p-mediated adaptation involves the binding of an unknown negative
      regulator to Gbetagamma.

PMID- 9539417
TI  - The yeast HSM3 gene acts in one of the mismatch repair pathways.
AB  - Mutants with enhanced spontaneous mutability (hsm) to canavanine resistance were
      induced by N-methyl-N-nitrosourea in Saccharomyces cerevisiae. One bearing the
      hsm3-1 mutation was used for this study. This mutation does not increase
      sensitivity to the lethal action of different mutagens. The hsm3-1 mutation
      produces a mutator phenotype, enhancing the rates of spontaneous mutation to
      canavanine resistance and reversions of lys1-1 and his1-7. This mutation
      increases the rate of intragenic mitotic recombination at the ADE2 gene. The
      ability of the hsm3 mutant to correct DNA heteroduplex is reduced in comparison
      with the wild-type strain. All these phenotypes are similar to ones caused by
      pms1, mlhl and msh2 mutations. In contrast to these mutations, hsm3-1 increases
      the frequency of ade mutations induced by 6-HAP and UV light. Epistasis analysis
      of double mutants shows that the PMS1 and HSM3 genes control different mismatch
      repair systems. The HSM3 gene maps to the right arm of chromosome II, 25 cM
      distal to the HIS7 gene. Strains that bear a deleted open reading frame YBR272c
      have the genetic properties of the hsm3 mutant. The HSM3 product shows weak
      similarity to predicted products of the yeast MSH genes (homologs of the
      Escherichia coli mutS gene). The HSM3 gene may be a member of the yeast MutS
      homolog family, but its function in DNA metabolism differs from the functions of
      other yeast MutS homologs.

PMID- 9539418
TI  - Radiation-induced chromosome aberrations in Saccharomyces cerevisiae: influence
      of DNA repair pathways.
AB  - Radiation-induced chromosome aberrations, particularly exchange-type aberrations,
      are thought to result from misrepair of DNA double-strand breaks. The
      relationship between individual pathways of break repair and aberration formation
      is not clear. By electrophoretic karyotyping of single-cell clones derived from
      irradiated cells, we have analyzed the induction of stable aberrations in haploid
      yeast cells mutated for the RAD52 gene, the RAD54 gene, the HDF1(= YKU70) gene,
      or combinations thereof. We found low and comparable frequencies of aberrational
      events in wildtype and hdf1 mutants, and assume that in these strains most of the
      survivors descended from cells that were in G2 phase during irradiation and
      therefore able to repair breaks by homologous recombination between sister
      chromatids. In the rad52 and the rad54 strains, enhanced formation of
      aberrations, mostly exchange-type aberrations, was detected, demonstrating the
      misrepair activity of a rejoining mechanism other than homologous recombination.
      No aberration was found in the rad52 hdf1 double mutant, and the frequency in the
      rad54 hdf1 mutant was very low. Hence, misrepair resulting in exchange-type
      aberrations depends largely on the presence of Hdf1, a component of the
      nonhomologous end-joining pathway in yeast.

PMID- 9539419
TI  - Genetic analysis of yeast RPA1 reveals its multiple functions in DNA metabolism.
AB  - Replication protein A (RPA) is a single-stranded DNA-binding protein identified
      as an essential factor for SV40 DNA replication in vitro. To understand the in
      vivo functions of RPA, we mutagenized the Saccharomyces cerevisiae RFA1 gene and
      identified 19 ultraviolet light (UV) irradiation- and methyl methane sulfonate
      (MMS)-sensitive mutants and 5 temperature-sensitive mutants. The UV- and MMS
      sensitive mutants showed up to 10(4) to 10(5) times increased sensitivity to
      these agents. Some of the UV- and MMS-sensitive mutants were killed by an HO
      induced double-strand break at MAT. Physical analysis of recombination in one UV-
      and MMS-sensitive rfa1 mutant demonstrated that it was defective for mating type
      switching and single-strand annealing recombination. Two temperature-sensitive
      mutants were characterized in detail, and at the restrictive temperature were
      found to have an arrest phenotype and DNA content indicative of incomplete DNA
      replication. DNA sequence analysis indicated that most of the mutations altered
      amino acids that were conserved between yeast, human, and Xenopus RPA1. Taken
      together, we conclude that RPA1 has multiple roles in vivo and functions in DNA
      replication, repair, and recombination, like the single-stranded DNA-binding
      proteins of bacteria and phages.

PMID- 9539420
TI  - Identification of GCD14 and GCD15, novel genes required for translational
      repression of GCN4 mRNA in Saccharomyces cerevisiae.
AB  - In Saccharomyces cerevisiae, expression of the transcriptional activator GCN4
      increases at the translational level in response to starvation for an amino acid.
      The products of multiple GCD genes are required for efficient repression of GCN4
      mRNA translation under nonstarvation conditions. The majority of the known GCD
      genes encode subunits of the general translation initiation factor eIF-2 or eIF
      2B. To identify additional initiation factors in yeast, we characterized 65
      spontaneously arising Gcd- mutants. In addition to the mutations that were
      complemented by known GCD genes or by GCN3, we isolated mutant alleles of two new
      genes named GCD14 and GCD15. Recessive mutations in these two genes led to highly
      unregulated GCN4 expression and to derepressed transcription of genes in the
      histidine biosynthetic pathway under GCN4 control. The derepression of GCN4
      expression in gcd14 and gcd15 mutants occurred with little or no increase in GCN4
      mRNA levels, and it was dependent on upstream open reading frames (uORFs) in GCN4
      mRNA that regulate its translation. We conclude that GCD14 and GCD15 are required
      for repression of GCN4 mRNA translation by the uORFs under conditions of amino
      acid sufficiency. The gcd14 and gcd15 mutations confer a slow-growth phenotype on
      nutrient-rich medium, and gcd15 mutations are lethal when combined with a
      mutation in gcd13. Like other known GCD genes, GCD14 and GCD15 are therefore
      probably required for general translation initiation in addition to their roles
      in GCN4-specific translational control.

PMID- 9539421
TI  - Theme and variation among silencing proteins in Saccharomyces cerevisiae and
      Kluyveromyces lactis.
AB  - The cryptic mating type loci in Saccharomyces cerevisiae act as reservoirs of
      mating type information used in mating type switching in homothallic yeast
      strains. The transcriptional silencing of these loci depends on the formation of
      a repressive chromatin structure that is reminiscent of heterochromatin. Silent
      information regulator (Sir) proteins 2-4 are absolutely required for silencing.
      To learn more about silencing, we investigated mating type and Sir proteins in
      the yeast Kluyveromyces lactis, which contains cryptic copies of the mating type
      genes. A functional homolog of SIR4 from K. lactis complements the silencing
      defect of sir4 null mutations in S. cerevisiae. K. lactis sir2 and sir4 mutant
      strains showed partial derepression of the silent alpha1 gene, establishing that
      the silencing role of these proteins is conserved. K. lactis sir2 mutants are
      more sensitive than the wild type to ethidium bromide, and K. lactis sir4 mutants
      are more resistant phenotypes that are not observed for the corresponding mutants
      of S. cerevisiae. Finally, the deletion of sir4 in the two yeasts leads to
      opposite effects on telomere length. Thus, Sir proteins from K. lactis have roles
      in both silencing and telomere length maintenance, reflecting conserved
      functional themes. The various phenotypes of sir mutants in K. lactis and S.
      cerevisiae, however, revealed unanticipated variation between their precise
      roles.

PMID- 9539422
TI  - The Neurospora rca-1 gene complements an Aspergillus flbD sporulation mutant but
      has no identifiable role in Neurospora sporulation.
AB  - The Aspergillus nidulans flbD gene encodes a protein with a Myb-like DNA-binding
      domain that is proposed to act in concert with other developmental regulators to
      control initiation of conidiophore development. We have identified a Neurospora
      crassa gene called rca-1 (regulator of conidiation in Aspergillus) based on its
      sequence similarity to flbD. We found that N. crassa rca-1 can complement the
      conidiation defect of an A. nidulans flbD mutant and that induced expression of
      rca-1 caused conidiation in submerged A. nidulans cultures just as was previously
      observed for overexpression of flbD. Thus, the N. crassa gene appears to be a
      functional homologue of A. nidulans flbD and this is the first demonstration of
      functional complementation of an A. nidulans sporulation defect using a gene from
      an evolutionarily distant fungus. However, deletion of the rca-1 gene in N.
      crassa had no major effect on growth rate, macroconidiation, microconidiation, or
      ascospore formation. The only phenotype displayed by the rca-1 mutant was
      straight or counterclockwise hyphal growth rather than the clockwise spiral
      growth observed for wild type. Thus, if rca-1 is involved in N. crassa
      development, its role is subtle or redundant.

PMID- 9539423
TI  - Organization of chromosome ends in Ustilago maydis. RecQ-like helicase motifs at
      telomeric regions.
AB  - In this study we have established the structure of chromosome ends in the
      basidiomycete fungus Ustilago maydis. We isolated and characterized several
      clones containing telomeric regions and found that as in other organisms, they
      consist of middle repeated DNA sequences. Two principal types of sequence were
      found: UTASa was highly conserved in nucleotide sequence and located almost
      exclusively at the chromosome ends, and UTASb was less conserved in nucleotide
      sequence than UTASa and found not just at the ends but highly interspersed
      throughout the genome. Sequence analysis revealed that UTASa encodes an open
      reading frame containing helicase motifs with the strongest homology to RecQ
      helicases; these are DNA helicases whose function involves the maintenance of
      genome stability in Saccharomyces cerevisiae and in humans, and the suppression
      of illegitimate recombination in Escherichia coli. Both UTASa and UTASb contain a
      common region of about 300 bp located immediately adjacent to the telomere
      repeats that are also found interspersed in the genome. The analysis of the
      chromosome ends of U. maydis provides information on the general structure of
      chromosome ends in eukaryotes, and the putative RecQ helicase at UTASa may reveal
      a novel mechanism for the maintenance of chromosome stability.

PMID- 9539424
TI  - Regulation of septum formation in Aspergillus nidulans by a DNA damage checkpoint
      pathway.
AB  - In Aspergillus nidulans, germinating conidia undergo multiple rounds of nuclear
      division before the formation of the first septum. Previous characterization of
      temperature-sensitive sepB and sepJ mutations showed that although they block
      septation, they also cause moderate defects in chromosomal DNA metabolism.
      Results presented here demonstrate that a variety of other perturbations of
      chromosomal DNA metabolism also delay septum formation, suggesting that this is a
      general cellular response to the presence of sublethal DNA damage. Genetic
      evidence is provided that suggests that high levels of cyclin-dependent kinase
      (cdk) activity are required for septation in A. nidulans. Consistent with this
      notion, the inhibition of septum formation triggered by defects in chromosomal
      DNA metabolism depends upon Tyr-15 phosphorylation of the mitotic cdk p34nimX.
      Moreover, this response also requires elements of the DNA damage checkpoint
      pathway. A model is proposed that suggests that the DNA damage checkpoint
      response represents one of multiple sensory inputs that modulates p34nimX
      activity to control the timing of septum formation.

PMID- 9539425
TI  - Characterization of mat A-2, mat A-3 and deltamatA mating-type mutants of
      Neurospora crassa.
AB  - The mating-type locus of Neurospora crassa regulates mating identity and entry
      into the sexual cycle. The mat A idiomorph encodes three genes, mat A-1, mat A-2,
      and mat A-3. Mutations in mat A-1 result in strains that have lost mating
      identity and vegetative incompatibility with mat a strains. A strain containing
      mutations in both mat A-2 and mat A-3 is able to mate, but forms few ascospores.
      In this study, we describe the isolation and characterization of a mutant deleted
      for mat (deltamatA), as well as mutants in either mat A-2 or mat A-3. The
      deltamatA strain is morphologically wild type during vegetative growth, but it is
      sterile and heterokaryon compatible with both mat A and mat a strains. The mat A
      2 and mat A-3 mutants are also normal during vegetative growth, mate as a mat A
      strain, and produce abundant biparental asci in crosses with mat a, and are thus
      indistinguishable from a wild-type mat A strain. These data and the fact that the
      mat A-2 mat A-3 double mutant makes few asci with ascospores indicate that MAT A
      2 and MAT A-3 are redundant and may function in the same pathway. Analysis of the
      expression of two genes (sdv-1 and sdv-4) in the various mat mutants suggests
      that the mat A polypeptides function in concert to regulate the expression of
      some sexual development genes.

PMID- 9539426
TI  - A large pheromone and receptor gene complex determines multiple B mating type
      specificities in Coprinus cinereus.
AB  - Pheromone signaling plays an essential role in the mating and sexual development
      of mushroom fungi. Multiallelic genes encoding the peptide pheromones and their
      cognate 7-transmembrane helix (7-TM) receptors are sequestered in the B mating
      type locus. Here we describe the isolation of the B6 mating type locus of
      Coprinus cinereus. DNA sequencing and transformation analysis identified nine
      genes encoding three 7-TM receptors and six peptide pheromone precursors embedded
      within 17 kb of mating type-specific sequence. The arrangement of the nine genes
      suggests that there may be three functionally independent subfamilies of genes
      each comprising two pheromone genes and one receptor gene. None of the nine B6
      genes showed detectable homology to corresponding B gene sequences in the genomic
      DNA from a B3 strain, and each of the B6 genes independently alter B mating
      specificity when introduced into a B3 host strain. However, only genes in two of
      the B6 groups were able to activate B-regulated development in a B42 host.
      Southern blot analysis showed that these genes failed to cross-hybridize to
      corresponding genes in the B42 host, whereas the three genes of the third
      subfamily, which could not activate development in the B42 host, did cross
      hybridize. We conclude that cross-hybridization identifies the same alleles of a
      particular subfamily of genes in different B loci and that B6 and B42 share
      alleles of one subfamily. There are an estimated 79 B mating specificities: we
      suggest that it is the different allele combinations of gene subfamilies that
      generate these large numbers.

PMID- 9539428
TI  - High frequency intragenic recombination during macronuclear development in
      Tetrahymena thermophila restores the wild-type SerH1 gene.
AB  - Macronuclear development in ciliates is characterized by extensive rearrangement
      of genetic material, including sequence elimination, chromosome fragmentation and
      telomere addition. Intragenic recombination is a relatively rare, but
      evolutionarily important phenomenon occurring in mitosis and meiosis in a wide
      variety of organisms. Here, we show that high frequency intragenic recombination,
      on the order of 30%, occurs in the developing amitotic macronucleus of the
      ciliate Tetrahymena thermophila. Such recombination, occurring between two
      nonsense transition mutations separated by 726 nucleotides, reproducibly restores
      wild-type expression of the SerH1 surface protein gene, thus mimicking
      complementation in trans heterozygotes. Recombination must be considered a
      potentially important aspect of macronuclear development, producing gene
      combinations not present in the germinal micronucleus.

PMID- 9539427
TI  - The mitochondrial genome of the sea anemone Metridium senile (Cnidaria): introns,
      a paucity of tRNA genes, and a near-standard genetic code.
AB  - The circular, 17,443 nucleotide-pair mitochondrial (mt) DNA molecule of the sea
      anemone, Metridium senile (class Anthozoa, phylum Cnidaria) is presented. This
      molecule contains genes for 13 energy pathway proteins and two ribosomal (r) RNAs
      but, relative to other metazoan mtDNAs, has two unique features: only two
      transfer RNAs (tRNA(f-Met) and tRNA(Trp)) are encoded, and the cytochrome c
      oxidase subunit I (COI) and NADH dehydrogenase subunit 5 (ND5) genes each include
      a group I intron. The COI intron encodes a putative homing endonuclease, and the
      ND5 intron contains the molecule's ND1 and ND3 genes. Most of the unusual
      characteristics of other metazoan mtDNAs are not found in M. senile mtDNA:
      unorthodox translation initiation codons and partial translation termination
      codons are absent, the use of TGA to specify tryptophan is the only genetic code
      modification, and both encoded tRNAs have primary and secondary structures
      closely resembling those of standard tRNAs. Also, with regard to size and
      secondary structure potential, the mt-s-rRNA and mt-1-rRNA have the least
      deviation from Escherichia coli 16S and 23S rRNAs of all known metazoan mt-rRNAs.
      These observations indicate that most of the genetic variations previously
      reported in metazoan mtDNAs developed after Cnidaria diverged from the common
      ancestral line of all other Metazoa.

PMID- 9539429
TI  - Dictyostelium discoideum nuclear plasmid Ddp5 is a chimera related to the Ddp1
      and Ddp2 plasmid families.
AB  - The 14,955-bp Dictyostelium discoideum nuclear plasmid Ddp5 contains six
      transcribed open reading frames. One of these is related to the rep gene of the
      Ddp2 plasmid, and the other five are related to genes present on the Ddp1
      plasmid. The absence of a homolog of the Ddp1 G1 gene, coupled with the presence
      of the Ddp2 rep gene homolog and of a 1.6-kb inverted repeat analogous to the
      inverted repeats on members of the Ddp2 plasmid family, suggests that Ddp5 uses
      Ddp2-like replication and copy number control mechanisms and that it should be
      assigned to the Ddp2 plasmid family. Ddp5 carries genes homologous to the D1/D3
      and D2 genes of the Ddp1 plasmid as well as the Ddp1 G2/G3/D4, G5/D6, and
      G6/G4/D5 genes. The products of the Ddp5 G2-like, G5-like, and G6-like genes are
      likely to be transcription factors regulating the expression of themselves and of
      the other Ddp5 genes. The D1-like and D2-like genes may confer a selective
      advantage to plasmid-bearing cells, because they can be deleted from plasmid
      based shuttle vectors with no apparent effect on vector maintenance. Updated
      sequence information for the Ddp1 G5/D6, D1/D3, and D2 genes as well as the Dmp1
      and Dmp2 G5-like genes is presented. The locations of introns in the G5-like and
      D1-like genes of Ddp5 and in the homologous genes of the Ddp1, Dmp1, and Dmp2
      plasmids were identified. These introns all have GU at the 5' intron border and
      AG at the 3' intron border, are short (59 to 71 nucleotides), and are AT-rich. A
      conserved HHCC domain was identified in the G5 proteins; this is a putative zinc
      binding domain and may be involved in protein-DNA interaction.

PMID- 9539431
TI  - Mutant alleles of small effect are primarily responsible for the loss of fitness
      with slow inbreeding in Drosophila melanogaster.
AB  - Multilocus simulation is used to identify genetic models that can account for the
      observed rates of inbreeding and fitness decline in laboratory populations of
      Drosophila melanogaster. The experimental populations were maintained under
      crowded conditions for approximately 200 generations at a harmonic mean
      population size of Nh approximately 65-70. With a simulated population size of N
      = 50, and a mean selective disadvantage of homozygotes at individual loci
      approximately 1-2% or less, it is demonstrated that the mean effective population
      size over a 200-generation period may be considerably greater than N, with a
      ratio matching the experimental estimate of Ne/Nh approximately 1.4. The buildup
      of associative overdominance at electrophoretic marker loci is largely
      responsible for the stability of gene frequencies and the observed reduction in
      the rate of inbreeding, with apparent selection coefficients in favor of the
      heterozygote at neutral marker loci increasing rapidly over the first N
      generations of inbreeding to values approximately 5-10%. The observed decline in
      fitness under competitive conditions in populations of size approximately 50 in
      D. melanogaster therefore primarily results from mutant alleles with mean effects
      on fitness as homozygotes of sm < or = 0.02. Models with deleterious recessive
      mutants at the background loci require that the mean selection coefficient
      against heterozygotes is at most hsm approximately 0.002, with a minimum mutation
      rate for a single Drosophila autosome 100 cM in length estimated to be in the
      range 0.05-0.25, assuming an exponential distribution of s. A typical chromosome
      would be expected to carry at least 100-200 such mutant alleles contributing to
      the decline in competitive fitness with slow inbreeding.

PMID- 9539430
TI  - Genetic analysis of the Drosophila alphaPS2 integrin subunit reveals discrete
      adhesive, morphogenetic and sarcomeric functions.
AB  - The integrin family of cell surface receptors mediates cell-substrate and cell-to
      cell adhesion and transmits intracellular signals. In Drosophila there is good
      evidence for an adhesive role of integrins, but evidence for integrin signalling
      has remained elusive. Each integrin is an alphabeta heterodimer, and the
      Drosophila betaPS subunit forms at least two integrins by association with
      different alpha subunits: alphaPS1betaPS (PS1) and alphaPS2betaPS (PS2). The
      complex pattern of PS2 integrin expression includes, but is more extensive than,
      the sites where PS2 has a known requirement. In order to investigate whether PS2
      integrin is required at these additional sites and/or has functions besides
      mediating adhesion, a comprehensive genetic analysis of inflated, the gene that
      encodes alphaPS2, was performed. We isolated 35 new inflated alleles, and
      obtained 10 alleles from our colleagues. The majority of alleles are amorphs
      (36/45) or hypomorphs (4/45), but five alleles that affect specific developmental
      processes were identified. Interallelic complementation between these alleles
      suggests that some may affect distinct functional domains of the alphaPS2
      protein, which specify particular interactions that promote adhesion or
      signalling. One new allele reveals that the PS2 integrin is required for the
      development of the adult halteres and legs as well as the wing.

PMID- 9539432
TI  - Genetic and developmental characterization of Dmca1D, a calcium channel alpha1
      subunit gene in Drosophila melanogaster.
AB  - To begin unraveling the functional significance of calcium channel diversity, we
      identified mutations in Dmca1D, a Drosophila calcium channel alpha1 subunit cDNA
      that we recently cloned. These mutations constitute the l(2)35Fa lethal locus,
      which we rename Dmca1D. A severe allele, Dmca1D(X10), truncates the channel after
      the IV-S4 transmembrane domain. These mutants die as late embryos because they
      lack vigorous hatching movements. In the weaker allele, Dmca1D(AR66), a cysteine
      in transmembrane domain I-S1 is changed to tyrosine. Dmca1D(AR66) embryos hatch
      but pharate adults have difficulty eclosing. Those that do eclose have difficulty
      in fluid-filling of the wings. These studies show that this member of the calcium
      channel alpha1 subunit gene family plays a nonredundant, vital role in larvae and
      adults.

PMID- 9539433
TI  - Heterosis for viability, fecundity, and male fertility in Drosophila
      melanogaster: comparison of mutational and standing variation.
AB  - If genetic variation for fitness traits in natural populations ("standing"
      variation) is maintained by recurrent mutation, then quantitative-genetic
      properties of standing variation should resemble those of newly arisen mutations.
      One well-known property of standing variation for fitness traits is inbreeding
      depression, with its converse of heterosis or hybrid vigor. We measured heterosis
      for three fitness traits, pre-adult viability, female fecundity, and male
      fertility, among a set of inbred Drosophilia melanogaster lines recently derived
      from the wild, and also among a set of lines that had been allowed to accumulate
      spontaneous mutations for over 200 generations. The inbred lines but not the
      mutation-accumulation (MA) lines showed heterosis for pre-adult viability. Both
      sets of lines showed heterosis for female fecundity, but heterosis for male
      fertility was weak or absent. Crosses among a subset of the MA lines showed that
      they were strongly differentiated for male fertility, with the differences
      inherited in autosomal fashion; the absence of heterosis for male fertility among
      the MA lines was therefore not caused by an absence of mutations affecting this
      trait. Crosses among the inbred lines also gave some, albeit equivocal, evidence
      for male fertility variation. The contrast between the results for female
      fecundity and those for male fertility suggests that mutations affecting
      different fitness traits may differ in their average dominance properties, and
      that such differences may be reflected in properties of standing variation. The
      strong differentiation among the MA lines in male fertility further suggests that
      mutations affecting this trait occur at a high rate.

PMID- 9539434
TI  - Genetic analysis of Drosophila larval optic nerve development.
AB  - To identify genes necessary for establishing connections in the Drosophila
      sensory nervous system, we designed a screen for mutations affecting development
      of the larval visual system. The larval visual system has a simple and
      stereotypic morphology, can be recognized histologically by a variety of
      techniques, and is unnecessary for viability. Therefore, it provides an
      opportunity to identify genes involved in all stages of development of a simple,
      specific neuronal connection. By direct observation of the larval visual system
      in mutant embryos, we identified 24 mutations affecting its development; 13 of
      these are larval visual system-specific. These 13 mutations can be grouped
      phenotypically into five classes based on their effects on location, path or
      morphology of the larval visual system nerves and organs. These mutants and
      phenotypic classifications provide a context for further analysis of neuronal
      development, pathfinding and target recognition.

PMID- 9539435
TI  - Quantitative trait loci for honey bee stinging behavior and body size.
AB  - A study was conducted to identify quantitative trait loci (QTLs) that affect
      colony-level stinging behavior and individual body size of honey bees. An F1
      queen was produced from a cross between a queen of European origin and a drone
      descended from an African subspecies. Haploid drones from the hybrid queen were
      individually backcrossed to sister European queens to produce 172 colonies with
      backcross workers that were evaluated for tendency to sting. Random amplified
      polymorphic DNA markers were scored from the haploid drone fathers of these
      colonies. Wings of workers and drones were used as a measure of body size because
      Africanized bees in the Americas are smaller than European bees. Standard
      interval mapping and multiple QTL models were used to analyze data. One possible
      QTL was identified with a significant effect on tendency to sting (LOD 3.57).
      Four other suggestive QTLs were also observed (about LOD 1.5). Possible QTLs also
      were identified that affect body size and were unlinked to defensive-behavior
      QTLs. Two of these were significant (LOD 3.54 and 5.15).

PMID- 9539437
TI  - A genetic linkage map of a cichlid fish, the tilapia (Oreochromis niloticus).
AB  - We have constructed a genetic map for a tilapia, Oreochromis niloticus, using DNA
      markers. The segregation of 62 microsatellite and 112 anonymous fragment length
      polymorphisms (AFLPs) was studied in 41 haploid embryos derived from a single
      female. We have identified linkages among 162 (93.1%) of these markers. 95% of
      the microsatellites and 92% of the AFLPs were linked in the final map. The map
      spans 704 Kosambi cM in 30 linkage groups covering the 22 chromosomes of this
      species. Twenty-four of these linkage groups contain at least one microsatellite
      polymorphism. From the number of markers 15 or fewer cM apart, we estimate a
      total map length of approximately 1000-1200 cM. High levels of interference are
      observed, consistent with measurements in other fish species. This map is a
      starting point for the mapping of single loci and quantitative traits in cichlid
      fishes.

PMID- 9539436
TI  - Ribosomal protein insufficiency and the minute syndrome in Drosophila: a dose
      response relationship.
AB  - Minutes comprise > 50 phenotypically similar mutations scattered throughout the
      genome of Drosophila, many of which are identified as mutations in ribosomal
      protein (rp) genes. Common traits of the Minute phenotype are short and thin
      bristles, slow development, and recessive lethality. By mobilizing a P element
      inserted in the 5' UTR of M(3)95A, the gene encoding ribosomal protein S3 (RPS3),
      we have generated two homozygous viable heteroalleles that are partial revertants
      with respect to the Minute phenotype. Molecular characterization revealed both
      alleles to be imprecise excisions, leaving 40 and 110 bp, respectively, at the P
      element insertion site. The weaker allele (40 bp insert) is associated with a
      approximately 15% decrease in RPS3 mRNA abundance and displays a moderate Minute
      phenotype. In the stronger allele (110 bp insert) RPS3 mRNA levels are reduced by
      approximately 60%, resulting in an extreme Minute phenotype that includes many
      morphological abnormalities as well as sterility in both males and females due to
      disruption of early gametogenesis. The results show that there is a correlation
      between reduced RPS3 mRNA levels and the severity of the Minute phenotype, in
      which faulty differentiation of somatic tissues and arrest of gametogenesis
      represent the extreme case. That heteroalleles in M(3)95A can mimic the
      phenotypic variations that exist between different Minute/rp-gene mutations
      strongly suggests that all phenotypes primarily are caused by reductions in
      maximum protein synthesis rates, but that the sensitivity for reduced levels of
      the individual rp-gene products is different.

PMID- 9539438
TI  - Genetic variation and causes of genotype-environment interaction in the body size
      of blue tit (Parus caeruleus).
AB  - In several studies of natural populations of birds, the heritability of body size
      estimated by parent-offspring regression has been lower when offspring have
      developed in poor feeding regimens than when they developed in good feeding
      regimens. This has led to the suggestion that adaptation under poor regimens may
      be constrained by lack of genetic variation. We examined the influence of
      environmental conditions on expression of genetic variation in body size of
      nestling blue tits (Parus caeruleus) by raising full sibs in artificially reduced
      and enlarged broods, corresponding to good and poor feeding regimens,
      respectively. Individuals grown in the poor regimen attained smaller body size
      than their sibs grown in the good regimen. However, there was among-family
      variation in response to the treatments--i.e., genotype-environment interactions
      (GEIs). Partitioning the GEI variance into contributions attributable to (1)
      differences in the among-family genetic variance between the treatments and (2)
      imperfect correlation of genotypic values across treatments identified the latter
      as the main cause of the GEI. Parent-offspring regressions were not significantly
      different when offspring were reared in the good environment (h2 = 0.75) vs. when
      they were reared in the poor environment (h2 = 0.63). Thus, there was little
      evidence that genetic variance in body size was lower under the poor conditions
      than under the good conditions. These results do not support the view that the
      genetic potential for adaptation to poor feeding conditions is less than that for
      adaptation to good conditions, but they do suggest that different genotypes may
      be favored under the different conditions.

PMID- 9539439
TI  - Patterns of Y and X chromosome DNA sequence divergence during the Felidae
      radiation.
AB  - The 37 species of modern cats have evolved from approximately eight phylogenetic
      lineages within the past 10 to 15 million years. The Felidae family has been
      described with multiple measures of morphologic and molecular evolutionary
      methods that serve as a framework for tracking gene divergence during brief
      evolutionary periods. In this report, we compare the mode and tempo of evolution
      of noncoding sequences of a large intron within Zfy (783 bp) and Zfx (854 bp),
      homologous genes located on the felid Y and X chromosomes, respectively. Zfy
      sequence variation evolves at about twice the rate of Zfx, and both gene intron
      sequences track feline hierarchical topologies accurately. As homoplasies are
      infrequent in patterns of nucleotide substitution, the Y chromosome sequence
      displays a remarkable degree of phylogenetic consistency among cat species and
      provides a highly informative glimpse of divergence of sex chromosome sequences
      in Felidae.

PMID- 9539440
TI  - Biased short tract repair of palindromic loop mismatches in mammalian cells.
AB  - Mismatch repair of palindromic loops in the presence or absence of single-base
      mismatches was investigated in wild-type and mismatch-binding defective mutant
      Chinese hamster ovary cells. Recombination intermediates with a maximum
      heteroduplex DNA (hDNA) region of 697 bp contained a centrally located,
      phenotypically silent 12-base palindromic loop mismatch, and/or five single-base
      mismatches. In wild-type cells, both loops and single-base mismatches were
      efficiently repaired (80-100%). When no other mismatches were present in hDNA,
      loops were retained with a 1.6-1.9:1 bias. However, this bias was eliminated when
      single-base mismatches were present, perhaps because single-base mismatches
      signal nick-directed repair. In the multiple marker crosses, most repair tracts
      were long and continuous, with preferential loss of markers in cis to proximal
      nicks, consistent with nicks directing most repair in this situation. However,
      approximately 25% of repair tracts were discontinuous as a result of loop
      specific repair, or from segregation or short tract repair of single-base
      mismatches. In mutant cells, single-base mismatches were repaired less
      frequently, but the loop was still repaired efficiently and with bias toward loop
      retention, indicating that the defect in these cells does not affect loop
      specific repair. Repair tracts in products from mutant cells showed a wide
      variety of mosaic patterns reflecting short regions of repair and segregation
      consistent with reduced nick-directed repair. In mutant cells, single-base
      mismatches were repaired more efficiently in the presence of the loop than in its
      absence, a likely consequence of corepair initiated at the loop.

PMID- 9539441
TI  - Heterogeneity of microsatellite mutations within and between loci, and
      implications for human demographic histories.
AB  - Microsatellites have been widely used to reconstruct human evolution. However,
      the efficient use of these markers relies on information regarding the process
      producing the observed variation. Here, we present a novel approach to the locus
      by-locus characterization of this process. By analyzing somatic mutations in
      cancer patients, we estimated the distributions of mutation size for each of 20
      loci. The same loci were then typed in three ethnically diverse population
      samples. The generalized stepwise mutation model was used to test the predicted
      relationship between population and mutation parameters under two demographic
      scenarios: constant population size and rapid expansion. The agreement between
      the observed and expected relationship between population and mutation
      parameters, even when the latter are estimated in cancer patients, confirms that
      somatic mutations may be useful for investigating the process underlying
      population variation. Estimated distributions of mutation size differ
      substantially amongst loci, and mutations of more than one repeat unit are
      common. A new statistic, the normalized population variance, is introduced for
      multilocus estimation of demographic parameters, and for testing demographic
      scenarios. The observed population variation is not consistent with a constant
      population size. Time estimates of the putative population expansion are in
      agreement with those obtained by other methods.

PMID- 9539442
TI  - Effect of the pairing gene Ph1 on centromere misdivision in common wheat.
AB  - The cytologically diploid-like meiotic behavior of hexaploid wheat (i.e.,
      exclusive bivalent pairing of homologues) is largely controlled by the pairing
      homoeologous gene Ph1. This gene suppresses pairing between homoeologous
      (partially homologous) chromosomes of the three closely related genomes that
      compose the hexaploid wheat complement. It has been previously proposed that Ph1
      regulates meiotic pairing by determining the pattern of premeiotic arrangement of
      homologous and homoeologous chromosomes. We therefore assume that Ph1 action may
      be targeted at the interaction of centromeres with spindle microtubules--an
      interaction that is critical for movement of chromosomes to their specific
      interphase positions. Using monosomic lines of common wheat, we studied the
      effect of this gene on types and rates of centromere division of univalents at
      meiosis. In the presence of the normal two doses of Ph1, the frequency of
      transverse breakage (misdivision) of the centromere of univalent chromosomes was
      high in both first and second meiotic divisions; whereas with zero dose of the
      gene, this frequency was drastically reduced. The results suggest that Ph1 is a
      trans-acting gene affecting centromere-microtubules interaction. The findings are
      discussed in the context of the effect of Ph1 on interphase chromosome
      arrangement.

PMID- 9539445
TI  - Fixation indices in subdivided populations.
AB  - Without restricting the evolutionary forces that may be present, the theory of
      fixation indices, or F-statistics, in an arbitrarily subdivided population is
      developed systematically in terms of allelic and genotypic frequencies. The
      fixation indices for each homozygous genotype are expressed in terms of the
      fixation indices for the heterozygous genotypes. Therefore, together with the
      allelic frequencies, the latter suffice to describe population structure.
      Possible random fluctuations in the allelic frequencies (which may be caused,
      e.g., by finiteness of the subpopulations) are incorporated so that the fixation
      indices are parameters, rather than random variables, and these parameters are
      expressed in terms of ratios of evolutionary expectations of heterozygosities.
      The interpretation of some measures of population differentiation is also
      discussed. In particular, F(ST) is an appropriate index of gene-frequency
      differentiation if and only if the genetic diversity is low.

PMID- 9539444
TI  - Genetic variation within and among populations of Arabidopsis thaliana.
AB  - We investigated levels of nucleotide polymorphism within and among populations of
      the highly self-fertilizing Brassicaceous species, Arabidopsis thaliana. Four
      cutter RFLP data were collected at one mitochondrial and three nuclear loci from
      115 isolines representing 11 worldwide population collections, as well as from
      seven commonly used ecotypes. The collections include multiple populations from
      North America and Eurasia, as well as two pairs of collections from locally
      proximate sites, and thus allow a hierarchical geographic analysis of
      polymorphism. We found no variation at the mitochondrial locus Nad5 and very low
      levels of intrapopulation nucleotide diversity at Adh, Dhs1, and Gpa1.
      Interpopulation nucleotide diversity was also consistently low among the loci,
      averaging 0.0014. gst, a measure of population differentiation, was estimated to
      be 0.643. Interestingly, we found no association between geographical distance
      between populations and genetic distance. Most haplotypes have a worldwide
      distribution, suggesting a recent expansion of the species or long-distance gene
      flow. The low level of polymorphism found in this study is consistent with
      theoretical models of neutral mutations and background selection in highly self
      fertilizing species.

PMID- 9539443
TI  - Suppressors of an Arabidopsis thaliana phyB mutation identify genes that control
      light signaling and hypocotyl elongation.
AB  - Ambient light controls the development and physiology of plants. The Arabidopsis
      thaliana photoreceptor phytochrome B (PHYB) regulates developmental light
      responses at both seedling and adult stages. To identify genes that mediate
      control of development by light, we screened for suppressors of the long
      hypocotyl phenotype caused by a phyB mutation. Genetic analyses show that the shy
      (short hypocotyl) mutations we have isolated fall in several loci. Phenotypes of
      the mutants suggest that some of the genes identified have functions in control
      of light responses. Other loci specifically affect cell elongation or expansion.

PMID- 9539446
TI  - Conditions for positive and negative correlations between fitness and
      heterozygosity in equilibrium populations.
AB  - The past decades have witnessed extensive efforts to correlate fitness traits
      with genomic heterozygosity. While positive correlations are revealed in most of
      the organisms studied, results of no/negative correlations are not uncommon.
      There has been little effort to reveal the genetic causes of these negative
      correlations. The positive correlations are regarded either as evidence for
      functional overdominance in large, randomly mating populations at equilibrium, or
      the results of populations at disequilibrium under dominance. More often, the
      positive correlations are viewed as a phenomenon of heterosis, so that it cannot
      possibly occur under within-locus additive allelic effects. Here we give exact
      genetic conditions that give rise to positive and negative correlations in
      populations at Hardy-Weinberg and linkage equilibria, thus offering a genetic
      explanation for the observed negative correlations. Our results demonstrate that
      the above interpretations concerning the positive correlations are not complete
      or even necessary. Such a positive correlation can result under dominance and
      potentially under additivity, even in populations where associated overdominance
      due to linked alleles at different loci is not significant. Additionally,
      negative correlations and heterosis can co-occur in a single population. Although
      our emphasis is on equilibrium populations and for biallelic genetic systems, the
      basic conclusions are generalized to non-equilibrium populations and for multi
      allelic situations.

PMID- 9539447
TI  - Selection with recurrent backcrossing to develop congenic lines for quantitative
      trait loci analysis.
AB  - SEWALL WRIGHT suggested that genes of large effect on a quantitative trait could
      be isolated by recurrent backcrossing with selection on the trait. Loci
      [quantitative trait loci (QTL)] at which the recurrent and nonrecurrent lines
      have genes of different large effect on the trait would remain segregating, while
      other loci would become fixed for the gene carried by the recurrent parent. If
      the recurrent line is inbred and the backcrossing and selection is conducted in a
      series of replicate lines, in each of which only one backcross parent is selected
      for each generation, the lines will become congenic to the recurrent parent
      except for the QTL of large effect and closely linked regions of the genome, and
      these regions can be identified using a dense set of markers that differ between
      the parental lines. Such lines would be particularly valuable for subsequent fine
      scale mapping and gene cloning; but by chance, even QTL of large effect will be
      lost from some lines. The probability that QTL of specified effect remain
      segregating is computed as a function of its effect on the trait, the intensity
      of selection, and the number of generations of backcrossing. Analytical formulas
      are given for one or two loci, and simulation is used for more. It is shown that
      the method could have substantial discriminating ability and thus potential
      practical value.

PMID- 9539448
TI  - Marker-assisted selection efficiency in populations of finite size.
AB  - The efficiency of marker-assisted selection (MAS) based on an index incorporating
      both phenotypic and molecular information is evaluated with an analytical
      approach that takes into account the size of the experiment. We consider the case
      of a population derived from a cross between two homozygous lines, which is
      commonly used in plant breeding, and we study the relative efficiency of MAS
      compared with selection based only on phenotype in the first cycle of selection.
      It is shown that the selection of the markers included in the index leads to an
      overestimation of the effects associated with these markers. Taking this bias
      into account, we study the influence of several parameters, including experiment
      size and heritability, on MAS efficiency. Even if MAS appears to be most
      interesting for low heritabilities, we point out the existence of an optimal
      heritability (approximately 0.2) below which the low power of quantitative trait
      loci detection and the bias caused by the selection of markers reduce the
      efficiency. In this situation, increasing the power of detection by using a
      higher probability of type I error can improve MAS efficiency. This approach,
      validated by simulations, gives results that are generally consistent with those
      previously obtained by simulations using a more sophisticated biological model
      than ours. Thus, though developed from a simple genetic model, our approach may
      be a useful tool to optimize the experimental means for more complex genetic
      situations.

PMID- 9539449
TI  - The accuracy of marker-assisted selection for quantitative traits within
      populations in linkage equilibrium.
AB  - Using the concept of conditional coancestry, given observed markers, an explicit
      expression of the accuracy of marker-based selection is derived in situations of
      linkage equilibrium between markers and quantitative trait loci (QTL), for the
      general case of full-sib families nested within half-sib families. Such a
      selection scheme is rather inaccurate for moderate values of family sizes and QTL
      variance, and the accuracies predicted for linkage disequilibrium can never be
      reached. The result is used to predict the accuracy of marker-assisted combined
      selection (MACS) and is shown to agree with previous MACS results obtained by
      simulation of a best linear unbiased prediction animal model. Low gains in
      accuracy are generally to be expected compared to standard combined selection.
      The maximum gain, assuming infinite family size and all QTLs marked, is about
      50%.

PMID- 9539450
TI  - Bayesian mapping of multiple quantitative trait loci from incomplete inbred line
      cross data.
AB  - A novel fine structure mapping method for quantitative traits is presented. It is
      based on Bayesian modeling and inference, treating the number of quantitative
      trait loci (QTLs) as an unobserved random variable and using ideas similar to
      composite interval mapping to account for the effects of QTLs in other
      chromosomes. The method is introduced for inbred lines and it can be applied also
      in situations involving frequent missing genotypes. We propose that two new
      probabilistic measures be used to summarize the results from the statistical
      analysis: (1) the (posterior) QTL intensity, for estimating the number of QTLs in
      a chromosome and for localizing them into some particular chromosomal regions,
      and (2) the locationwise (posterior) distributions of the phenotypic effects of
      the QTLs. Both these measures will be viewed as functions of the putative QTL
      locus, over the marker range in the linkage group. The method is tested and
      compared with standard interval and composite interval mapping techniques by
      using simulated backcross progeny data. It is implemented as a software package.
      Its initial version is freely available for research purposes under the name
      Multimapper at URL http://www.rni.helsinki.fi/mjs.

PMID- 9539451
TI  - Genetic response from marker assisted selection in an outbred population for
      differing marker bracket sizes and with two identified quantitative trait loci.
AB  - Effect of flanking quantitative trait loci (QTL)-marker bracket size on genetic
      response to marker assisted selection in an outbred population was studied by
      simulation of a nucleus breeding scheme. In addition, genetic response with
      marker assisted selection (MAS) from two quantitative trait loci on the same and
      different chromosome(s) was investigated. QTL that explained either 5% or 10% of
      phenotypic variance were simulated. A polygenic component was simulated in
      addition to the quantitative trait loci. In total, 35% of the phenotypic variance
      was due to genetic factors. The trait was measured on females only. Having
      smaller marker brackets flanking the QTL increased the genetic response from MAS
      selection. This was due to the greater ability to trace the QTL transmission from
      one generation to the next with the smaller flanking QTL-marker bracket, which
      increased the accuracy of estimation of the QTL allelic effects. Greater negative
      covariance between effects at both QTL was observed when two QTL were located on
      the same chromosome compared to different chromosomes. Genetic response with MAS
      was greater when the QTL were on the same chromosome in the early generations and
      greater when they were on different chromosomes in the later generations of MAS.

PMID- 9539452
TI  - The effect of gene conversion on intralocus associations.

PMID- 9539453
TI  - Connections between polarization curves and log(a[i]/a[ref])-pe diagram.

PMID- 9539454
TI  - Dental extractions performed in HIV-positive patients.

PMID- 9539455
TI  - Carl Koller: mankind's greatest benefactor? The story of local anesthesia.

PMID- 9539456
TI  - Gustducin and its role in taste.
AB  - The mechanisms responsible for taste signal transductions are very complex. A key
      molecule, alpha-gustducin, a primarily taste-specific G protein alpha-subunit,
      was discovered in 1992 and was later found to be involved in both bitter and
      sweet taste transduction. A proposed mechanism for alpha-gustducin involves
      coupling specific cell-surface receptors with a cyclic nucleotide
      phosphodiesterase which would open a cyclic nucleotide-suppressible cation
      channel leading to influx of calcium, and ultimately leading to release of
      neurotransmitter. Although "knock-out" animals deficient in the alpha-gustducin
      gene clearly demonstrate that gustducin is an essential molecule for tasting
      certain bitter and sweet compounds, the precise role of alpha-gustducin in bitter
      and sweet taste is presently unclear. Indeed, there are several other signaling
      mechanisms in sweet and bitter taste, apparently unrelated to alpha-gustducin,
      that increase cyclic AMP or inositol 1,4,5 trisphosphate. Thus, proposed models
      for alpha-gustducin and those found by other laboratories may be parallel and
      interdependent.

PMID- 9539457
TI  - Bone morphogenetic protein-7 (osteogenic protein-1, OP-1) and tooth development.
AB  - Bone morphogenetic proteins (BMPs) form a family of growth factors originally
      isolated from extracellular bone matrix that are capable of inducing bone
      formation ectopically. We studied the expression, tissue localization, and
      function of BMP-7 (OP-1) during tooth development in rodents. Patterns of BMP-7
      gene expression and peptide distribution indicated that BMP-7 was present in
      dental epithelium during the dental lamina, bud, and cap stages. During the bell
      stage, BMP-7 mRNA expression and protein distribution shifted from dental
      epithelium toward the dental mesenchyme. With advancing differentiation of
      odontoblasts, BMP-7 protein staining in the dental papilla became restricted to
      the layer of fully functional odontoblasts in the process of depositing
      (pre)dentin. Secretory-stage ameloblasts exhibited weak immunostaining for BMP-7.
      A restricted pattern of staining in ameloblasts became apparent in post-secretory
      stages of amelogenesis. Also, cells of the forming periodontal ligament were
      immunopositive. Histological analysis of tooth development in neonatal BMP-7
      deficient mice did not reveal obvious changes compared with wild-type mice. We
      conclude that, in developing dental tissues, BMP-7 has distribution and
      expression patterns similar to those of other BMP members but is not an essential
      growth factor for tooth development, possibly because of functional redundancy
      with other BMP members or related growth factors.

PMID- 9539458
TI  - Flow cytometry analysis of gingival and periodontal ligament cells.
AB  - Gingival and periodontal ligament (PDL) fibroblasts are the major cellular
      components of periodontal soft connective tissues, but the precise differences
      between these cells are not yet known. In the present study, we have therefore
      examined the phenotypic and functional features of the cells obtained from
      gingival and PDL biopsy samples. Spindle-shaped cells characteristic of
      fibroblasts were the main cell type observed in vitro, although epithelial cells
      were also present in primary gingival cell cultures. Flow cytometry was used to
      measure the size and granularity of the cultured cells, and showed that the
      gingival fibroblasts were smaller and less granular compared with the PDL cells.
      The expression of certain key extracellular matrix (ECM) proteins, fibronectin,
      collagen type I, and tenascin was measured by flow cytometry. Analysis of the
      fluorescence profiles of these cultures showed that the majority of cells
      expressed fibronectin and that the average fluorescence intensity of this antigen
      in the PDL cells was higher than that in the gingival fibroblasts. Moreover, the
      fibronectin-positive PDL cells apparently comprised two subpopulations which
      expressed fibronectin at different levels, suggesting that the cells in the PDL
      cultures were functionally heterogeneous. The level of collagen type I was also
      found to be up-regulated in the PDL compared with the gingival cells and, as with
      fibronectin, was expressed at two different levels by subsets of the PDL cells.
      In contrast, tenascin was expressed at very similar levels by both the gingival
      fibroblasts and PDL cells. In addition, measurement of alkaline phosphatase, a
      marker enzyme for mineralized tissue-forming cells, showed that the PDL cells had
      higher activity than the gingival fibroblasts and that the alkaline phosphatase
      activity in the PDL cells was far more markedly up-regulated by dexamethasone.
      Our findings demonstrate that, despite their similar spindle-shaped appearance,
      fibroblasts derived from gingival and PDL tissues appear to display distinct
      functional activities which are likely to play a vital part in the maintenance of
      tissue integrity and regenerative processes.

PMID- 9539459
TI  - Sleep bruxism is a disorder related to periodic arousals during sleep.
AB  - There is evidence that sleep bruxism is an arousal-related phenomenon. In non-REM
      sleep, transient arousals recur at 20- to 40-second intervals and are organized
      according to a cyclic alternating pattern. Polysomnographic recordings from six
      subjects (two females and four males) affected by sleep bruxism (patients) and
      six healthy age-and gender-matched volunteers without complaints about sleep
      (controls) were analyzed to: (1) compare the sleep structure of bruxers with that
      of non-complaining subjects; and (2) investigate the relations between bruxism
      episodes and transient arousals. Patients and controls showed no significant
      differences in conventional sleep variables, but bruxers showed a significantly
      higher number of the transient arousals characterized by EEG desynchronization.
      Bruxism episodes were equally distributed between non-REM and REM sleep, but were
      more frequent in stages 1 and 2 (p < 0.0001) than in slow-wave sleep. The great
      majority of bruxism episodes detected in non-REM sleep (88%) were associated with
      the cyclic alternating pattern and always occurred during a transient arousal.
      Heart rate during the bruxism episodes (69.3+/-18.2) was significantly higher (p
      < 0.0001) than that during the pre-bruxing period (58.1+/-15.9). Almost 80% of
      all bruxism episodes were associated with jerks at the anterior tibial muscles.
      The framework of the cyclic alternating pattern offers a unified interpretation
      for sleep bruxism and arousal-related phenomena.

PMID- 9539460
TI  - Food-holding and -biting behavior in human subjects lacking periodontal
      receptors.
AB  - Previous studies have suggested that information provided by periodontal
      mechanoreceptors is particularly important for the fine motor control of the
      mandible, i.e., when humans hold and carefully manipulate food particles between
      the teeth with low biting forces. In the present study, we further evaluated this
      hypothesis by comparing the performance of three age- and gender-matched groups
      of subjects for which the integrity of the periodontal sensory apparatus
      differed. Specifically, the subjects had either natural teeth (natural group),
      dental prostheses supported by oral mucosa (denture group), or dental prostheses
      supported by osseointegrated implants (implant group). Each subject was
      instructed to hold half a peanut between the upper and lower central incisors for
      ca. 3 sec, and then to split it. The force applied by the anterior teeth was
      continuously monitored by a transducer-equipped bar on which the morsel rested.
      While the peanut was held, the force generated by subjects in the denture and
      implant groups was more variable and averaged four times that generated by
      subjects in the natural group. The peanut was split by a distinct, rapid ramp
      increase in force that was similar for all three groups. In subjects lacking
      periodontal receptors, the morsel frequently escaped from the incisal edges
      during both phases of the task. The results demonstrate a marked disturbance in
      the control of precisely directed, low biting forces in subjects lacking
      periodontal receptors and suggest that the receptors play a significant role in
      the specification of the level, direction, and point of attack of forces used to
      hold and manipulate food between the anterior teeth. Moreover, other types of
      mechanoreceptors can not fully compensate for the loss of periodontal receptors.

PMID- 9539461
TI  - Effect of ion exchange on the microstructure, strength, and thermal expansion
      behavior of a leucite-reinforced porcelain.
AB  - Leucite (KAlSi2O6) is used as a reinforcing agent in some porcelains for all
      ceramic restorations; however, it increases their coefficients of thermal
      expansion, imposing constraints on the processing of the material. The potassium
      ions in leucite are exchangeable for rubidium or cesium ions, leading to rubidium
      leucite or cesium leucite (pollucite). Both rubidium leucite and pollucite
      exhibit a lower coefficient of thermal expansion and inversion temperature than
      leucite. The purpose of this study was to evaluate the effects of rubidium and
      cesium leucites on thermal expansion, microstructure, crack deflection patterns,
      and flexural strength of a leucite-reinforced porcelain. A dental porcelain
      powder was mixed with rubidium or cesium nitrate and heat-treated. Porcelain bars
      (n = 3) and discs (n = 15) were made with the exchanged powders. X-ray
      diffraction analyses were performed before and after bars were fired. Controls
      were made of untreated Optec HSP porcelain powder, formed into bars and disks,
      and baked following manufacturer's recommendations. The density of all specimens
      was determined by Archimedes' method. The thermal expansion behavior of the
      materials was measured by dilatometry. The microstructure and Vickers indentation
      crack patterns were investigated by scanning electron microscopy. X-ray
      diffraction showed that after ion-exchange and firing, leucite transformed into
      either tetragonal rubidium leucite or cubic cesium leucite. The mean coefficient
      of thermal contraction (550 to 50 degrees C) was significantly (p < 0.003)
      greater for the control material, followed by the rubidium-exchanged material,
      and lowest for the cesium-exchanged material. Crack pattern analyses revealed
      that the cesium-exchanged material exhibited a significantly lower number of
      crack deflections compared with those in the two other materials (p < 0.001). The
      microstructure of the two exchanged porcelain materials was dense, with well
      dispersed small crystals as well as larger rubidium or cesium leucite crystals.
      The mean flexural strength of the rubidium-exchanged material was significantly
      higher than those of the other materials, which were not significantly different.
      It was concluded that the thermal expansion of leucite-reinforced porcelain can
      be lowered by ion-exchange, which also modifies the microstructure, crack
      deflection patterns, and flexural strength of the material.

PMID- 9539462
TI  - Mechanical characterization of dental ceramics by hertzian contacts.
AB  - Hertzian indentation testing is proposed as a protocol for evaluating the role of
      microstructure in the mechanical response of dental ceramics. A major advantage
      of Hertzian indentation over more traditional fracture-testing methodologies is
      that it emulates the loading conditions experienced by dental restorations:
      Clinical variables (masticatory force and cuspal curvature) identify closely with
      Hertzian variables (contact load and sphere radius). In this paper, Hertzian
      responses on four generic dental ceramics systems-micaceous glass-ceramics, glass
      infiltrated alumina, feldspathic porcelain, and transformable zirconiaare
      presented as case studies. Ceramographic sectioning by means of a "bonded
      interface" technique provides new information on the contact damage modes. Two
      distinct modes are observed: "brittle" mode, classic macroscopic fracture outside
      the contact (ring, or cone cracks), driven by tensile stresses; and "quasi
      plastic" mode, a relatively new kind of deformation below the contact (diffuse
      microdamage), driven by shear stresses. A progressive transition from the first
      to the second mode with increasing microstructural heterogeneity is observed. The
      degree of quasi-plasticity is readily apparent as deviations from ideal linear
      elastic responses on indentation stress-strain curves. Plots of threshold loads
      for the initiation of both fracture and deformation modes as a function of
      indenter radius constitute "damage maps" for the evaluation of prospective
      restoration damage under typical masticatory conditions. The degree of damage in
      both modes evolves progressively with load above the thresholds. Strength tests
      on indented specimens quantify sustainable stress levels on restoration materials
      after damage. The most brittle responses are observed in the fine glass-ceramics
      and porcelain; conversely, the most quasi-plastic responses are observed in the
      coarse glass-ceramics and zirconia; the medium glass-ceramics and alumina exhibit
      intermediate responses. Implications of the results in relation to future
      materials characterization, selection, and design are considered in the clinical
      context.

PMID- 9539463
TI  - Elements of light-cured epoxy-based dental polymer systems.
AB  - The greatest problem with current dental composite systems is their
      polymerization shrinkage. Extensive work is being done by many investigators to
      alleviate this problem. Our approach has been to examine epoxy- and spiro
      orthocarbonate (SOC)-based resins. The hypothesis to be tested in this study was
      that the cure characteristics of experimental visible-light-cured epoxy resin
      systems are governed by the types and concentrations of co-reactants and
      activators. Resin samples containing onium salt initiators and a thiozanthone
      sensitizer were successfully cured by means of either an experimental visible
      light irradiation system or a commercially available dental lamp. Test resins
      consisted of di-epoxies alone or in combination, epoxy mixtures in combination
      with an SOC, or an epoxy in combination with a caprolactone-derived polyol.
      Significant findings were as follows: (a) Resins containing the SOC had longer
      cure times than their counterparts; (b) the optimum ratios of epoxy to polyol for
      most rapid cure were 50:50 or 60:40 under conditions tested; (c) resins
      containing TONE 305 polyol generally were faster to cure than those containing no
      polyol, or TONES 201 or 310; and (d) a resin mixture was found that had a cure
      time of 1 to 3 min when irradiated with a commercial dental lamp. Based on this
      exploratory study, it should be possible for clinically relevant cure times to be
      achieved for visible-light-cured epoxy-based resins by careful manipulation and
      optimization of key elements.

PMID- 9539464
TI  - A five-year multi-practice clinical study on posterior resin-bonded bridges.
AB  - Previous clinical observations have revealed that resin-bonded bridges for
      posterior tooth replacements are less retentive than anterior resin-bonded
      bridges. Improved bonding procedures and preparation designs, however, may have a
      positive effect on the functional durability of these restorations. The present
      study reports the final analysis of a randomized controlled clinical trial in
      which different designs of posterior resin-bonded bridges were evaluated for a
      period of at least 5 years. The operational hypothesis was that the bonding
      system and the preparation design used in posterior resin-bonded bridges have an
      influence on the survival and clinical functioning of these restorations.
      Survival in this study was defined at two levels: (1) 'complete' survival
      (survival without any debonding), and (2) 'functional' survival (survival
      including loss of retention on one occasion and successful rebonding of the
      original RBB without further debonding). With regard to 'complete' survival, no
      significant differences were found between the bonding systems used for adherence
      of the restorations to abutment teeth (etching/Clearfil F2, sandblasting/Panavia
      EX, and silica-coating/Microfill Pontic C). The variable 'preparation form'
      (conventional preparation form vs. modified preparation form) for complete
      survival was statistically in favor of the modified preparation form (62% vs.
      46%), but did not influence the functional survival. With regard to 'functional'
      survival, the combination of silica coating and Microfill Pontic C was more
      retentive than the other bonding systems (90% survival vs. 72% and 75%, p <
      0.01). Factor location was found to be highly significant for both survival
      levels [Cox's PH model, p = 0.0002 (Cox, 1972)]: The five-year 'complete'
      survival rates were 65% for maxillary restorations and 40% for mandibular
      restorations, while the five-year 'functional' survival rates were 89% and 68%,
      respectively. It is concluded that preparation of grooves in abutment teeth for
      posterior resin-bonded bridges is beneficial to their chance of survival. Resin
      bonded bridges placed in the maxilla have a better prognosis than those made in
      the mandible. The bonding systems used in this study appear to have no influence
      on the chance of failure. In rebonded posterior resin-bonded bridges, the bonding
      system silica-coating/Microfill Pontic C was more retentive than the other
      systems tested.

PMID- 9539466
TI  - Impact of structural heart disease on the selection of class III antiarrhythmics
      for the prevention of atrial fibrillation and flutter.
AB  - Antiarrhythmic agents may be beneficial or harmful. Among the harmful effects, or
      risks, is proarrhythmia. One of several factors that underlie proarrhythmic risk
      is the presence and nature of any underlying structural heart disease at the time
      of antiarrhythmic drug administration. The structural disease-antiarrhythmic drug
      interaction has been best studied and clearly delineated for class I
      antiarrhythmics. This review provides information to suggest that structural
      disease can enhance proarrhythmic risk with class III drugs as well, although
      this is least evident with amiodarone. Particularly pertinent are disorders that
      prolong action potential duration (such as ventricular hypertrophy or chronic
      dilatation), inhomogeneous dispersion of refractoriness (including conditions
      with cellular uncoupling), and reduced ventricular fibrillation threshold. These
      issues must be considered when choosing an antiarrhythmic drug for atrial and for
      ventricular arrhythmias and when selecting the dosing and monitoring protocol to
      be used.

PMID- 9539465
TI  - Mercury in biological fluids after amalgam removal.
AB  - Dental amalgam is the major source of inorganic mercury (Hg) exposure in the
      general population. The objective of the present study was to obtain data on
      changes in Hg levels in blood, plasma, and urine following removal of all amalgam
      fillings during one dental session in 12 healthy subjects. The mean number of
      amalgam surfaces was 18 (range, 13 to 34). Frequent blood sampling and 24-hour
      urine collections were performed up to 115 days after amalgam removal, and in
      eight subjects additional samples of plasma and urine were collected up to three
      years after amalgam removal. A transient increase of Hg concentrations in blood
      and plasma was observed within 48 hours after amalgam removal. In plasma, the
      peak concentrations significantly exceeded the pre-removal plasma Hg levels by,
      on average, 32% (1.3 nmol/L; range, 0.1 to 4.2). No increase in the urinary Hg
      excretion rate was apparent after amalgam removal. An exponential decline of Hg
      was seen in all media. Sixty days after the amalgam removal, the Hg levels in
      blood, plasma, and urine had declined to approximately 60% of the pre-removal
      levels. In seven subjects, who were followed for up to three years, the half
      lives of Hg in plasma and urine were calculated. In plasma, a bi-exponential
      model was applied, and the half-life was estimated at median 88 days (range, 21
      to 121). The kinetics of Hg in urine (nmol/24 hrs) fit a mono-exponential model
      with a median half-life of 46 days (range, 35 to 67). It is concluded that the
      process of removing amalgam fillings can have a considerable impact on Hg levels
      in biological fluids. After removal, there was a considerable decline in the Hg
      levels of blood, plasma, and urine, which slowly approached those of subjects
      without any history of amalgam fillings.

PMID- 9539467
TI  - Early discharge of patients with new-onset atrial fibrillation after
      cardiovascular surgery.
AB  - BACKGROUND: Atrial fibrillation is one of the most frequent complications after
      cardiovascular surgery. It may result in thromboembolic events, hemodynamic
      deterioration, and an increased length and cost of hospitalization. METHODS: We
      retrospectively studied 504 consecutive adult patients undergoing cardiovascular
      surgery to determine whether patients with new-onset postoperative atrial
      fibrillation could be safely discharged in atrial fibrillation after ventricular
      rate had been controlled and anticoagulation initiated. RESULTS: Postoperative
      atrial fibrillation occurred in 79 (16.2%) of the 487 survivors. Of these
      patients, 67 were discharged in sinus rhythm, whereas the remaining 12 were
      discharged in atrial fibrillation. Patients discharged in atrial fibrillation
      tended to be older, have higher Parsonnet risk scores, and have an increased
      incidence of valvular heart surgery. Despite this result, this cohort had a
      shorter length of hospital stay (7.3+/-2.0 days vs 10.9+/-9.3 days, p = 0.006),
      decreased hospital costs ($14,188+/-$2635 vs $23,016+/-$21,963, p = 0.002), and
      decreased hospital charges ($37,878+/-$7420 vs $58,289+/-$50,980, p = 0.003)
      compared with patients with atrial fibrillation discharged in sinus rhythm. In
      the 12 persons discharged home in atrial fibrillation, no repeat
      hospitalizations, bleeding complications, or thromboembolic events occurred.
      CONCLUSION: A strategy of early discharge of patients with persistent
      postoperative atrial fibrillation appears promising and deserves prospective
      testing on a larger scale.

PMID- 9539468
TI  - Shortened head-up tilt testing potentiated with sublingual nitroglycerin in
      patients with unexplained syncope.
AB  - BACKGROUND: Head-up tilt testing is extensively used to determine the vasovagal
      origin of syncope in patients with otherwise unexplained loss of consciousness,
      although issues remain regarding the method of the test. The diagnostic value of
      a shortened head-up tilt test potentiated with sublingual nitroglycerin was
      assessed in patients with unexplained syncope. METHODS: Two hundred two patients
      (mean age 49+/-19 years) with syncope of unknown origin and 34 subjects in a
      control group (mean age 45+/-17 years) were studied. The patients and the
      subjects in the control group were tilted upright to 60 degrees for 20 minutes.
      If syncope did not occur, sublingual nitroglycerin (400 microg) was administered,
      and observation was continued for 25 more minutes. RESULTS: During the
      unmedicated phase syncope occurred in 22 (11%) patients and in one member of the
      control group. After nitroglycerin was administered, syncope occurred in 119
      (59%) patients and in 1 (3%) member of the control group. False-positive response
      (exaggerated response) was observed in eight (4%) patients and in four (12%)
      subjects in the control group. The total positivity rate of the test was 70% with
      a specificity rate of 94%. CONCLUSIONS: Short-duration head-up tilt test
      potentiated with sublingual nitroglycerin provides an adequate specificity and
      positivity rate in patients with unexplained syncope.

PMID- 9539469
TI  - Depressed heart rate variability is associated with events in patients with
      stable coronary artery disease and preserved left ventricular function. REGRESS
      Study Group.
AB  - BACKGROUND: Little is known about the value of heart rate variability in patients
      with symptomatic coronary artery disease with a preserved left ventricular
      function. We hypothesized that in these patients heart rate variability might be
      a helpful adjunct to conventional parameters to predict clinical events. METHODS:
      In a prospective 2-year follow-up study ambulatory electrocardiographic
      recordings were performed in 263 consecutive male patients (mean age 56+/-8
      years) with stable angina pectoris and a mean left ventricular ejection fraction
      of 71%+/-12%. Clinical events consisted mainly of coronary events such as
      percutaneous transluminal angioplasty or coronary artery bypass graft operation.
      RESULTS: Low measures of standard deviation of normal R-R intervals, standard
      deviation of the mean R-R intervals of 5 minutes, and two spectral components of
      heart rate variability were found in patients who had had an event compared with
      patients with no event. Adjusted for severity of angina, the presence of a
      previous myocardial infarction, and the use of beta-blockers in a logistic
      regression model this relation remained statistically significant for SDNN.
      Healthy volunteers appeared to have the highest measures of heart rate
      variability. CONCLUSION: In patients with ischemic heart disease and normal or
      near normal ventricular function decreased heart rate variability is associated
      with adverse clinical events.

PMID- 9539470
TI  - Prospective evaluation of shoulder-related problems in patients with pectoral
      cardioverter-defibrillator implantation.
AB  - BACKGROUND: The pectoral approach to implantation of cardioverter defibrillators
      (ICDs) has become a standard in defibrillator therapy because of reduced
      generator size, weight, and volume. But the size of these devices is still
      comparable to the size of the early conventional antibradycardia pacemakers that
      were associated with a number of significant pocket- and shoulder-related
      problems after implantation in the pectoral region. In a prospective, single
      center study of 50 patients with subpectoral implantation of a fourth-generation
      ICD, the ipsilateral shoulder joint was evaluated regarding active shoulder
      motility, shoulder-related pain, shoulder function, shoulder elevation, insertion
      tendinitis, and morphologic alterations of the shoulder. METHODS AND RESULTS: The
      shoulder was evaluated before implantation and at 3, 6, and 12 months after
      implantation. Shoulder motility was documented by evaluating active abduction,
      forward flexion, and external rotation. Shoulder-related pain and function were
      documented by the "Basic Shoulder Evaluation Form," insertion tendinitis was
      diagnosed by standardized palpation and the impingement test, and morphologic
      alterations were documented by ultrasound and radiograph of the shoulder. Three
      months after implantation, 20 (40%) patients had a reduced active abduction, 30
      (60%) patients had an impaired active forward flexion, and eight (16%) patients
      had a reduced external rotation. Thirty-one (62%) patients reported shoulder
      related pain or impaired shoulder function according to the "Basic Shoulder
      Evaluation Form." Twenty-four (48%) patients showed a shoulder elevation and 21
      (42%) patients demonstrated clinical signs of insertion tendinitis. After 12
      months the number of patients with reduced active abduction, forward flexion, and
      external rotation dropped to four (8%). Shoulder-related pain and reduced
      function were documented in seven (13%) patients, four (8%) patients still had
      shoulder elevation, and five (10%) patients still had signs of insertion
      tendinitis. None of the postoperatively performed ultrasounds or radiographs
      showed any pathologic shoulder alterations. No predictors for the occurrence of
      shoulder-associated problems could be found. CONCLUSIONS: (1) Decreased active
      shoulder motility, shoulder-related pain, reduced function, shoulder elevation,
      and insertion tendinitis of the ipsilateral shoulder joint are diagnosed in many
      patients 3 months after subpectoral ICD implantation. (2) After 12 months the
      number of patients with impaired shoulder motility, function, shoulder-related
      pain, shoulder elevation, and insertion tendinitis decreased significantly. (3)
      Ultrasound and radiographs of the ipsilateral shoulder showed no evidence of
      pathologic morphologic alterations after subpectoral ICD implantation. (4) No
      shoulder-associated problems required an operative revision of the subpectoral
      generator pocket.

PMID- 9539471
TI  - Left ventricular inotropic and lusitropic responses to pacing-induced tachycardia
      in patients with varying degrees of ventricular dysfunction.
AB  - BACKGROUND: In the failing human heart contractile reserve during tachycardia is
      attenuated or absent. However, it is not known whether during tachycardia
      diminished inotropic reserve depends on the degree of ventricular dysfunction or
      lusitropic reserve is also diminished in patients with left ventricular (LV)
      dysfunction. METHODS: We studied 18 patients with dilated cardiomyopathy or
      mildly depressed LV function and 13 subjects in a control group (ejection
      fraction 0.67+/-0.09). The patients were classified into two groups based on
      whether their ejection fraction was less than or more than 0.40 (group 1,
      ejection fraction 0.27+/-0.05; group 2, ejection fraction 0.49+/-0.07). LV
      pressures were measured with a catheter-tip manometer during incremental right
      atrial pacing up to a heart rate of 150 beats/min. RESULTS: With incremental
      pacing LV peak positive dP/dt rose progressively in both the normal group and in
      group 2, but the increase was less for group 2 than for the normal group; in
      group 1 the increase was slight or absent. In contrast, a significant and
      progressive decrease occurred in the time constant of LV relaxation in all three
      groups. Although their values remained significantly different at each heart
      rate, no intergroup differences in absolute or percent changes were present.
      CONCLUSIONS: These findings suggest that during tachycardia LV inotropic reserve
      may be diminished depending on the degree of ventricular dysfunction, and
      lusitropic reserve may be preserved in patients with depressed function despite
      an attenuated inotropic response.

PMID- 9539472
TI  - Atrial natriuretic peptide release is more dependent on atrial filling volume
      than on filling pressure in chronic congestive heart failure.
AB  - BACKGROUND: The mechanism of atrial natriuretic peptide (ANP) release has been
      difficult to demonstrate in patient studies because of inaccuracies in measuring
      atrial volumes using conventional techniques. METHODS: Magnetic resonance imaging
      was performed in 28 clinically stable patients (New York Heart Association class
      3) with chronic heart failure to determine right atrial (RA), left atrial (LA),
      and ventricular volumes. In addition, right heart catheterization was serially
      performed and plasma ANP levels (in picograms per milliliter) were drawn from the
      right atrium. RESULTS: Five patients had to be excluded from data analysis for
      technical reasons. The remaining 23 patients had the following hemodynamic
      measurements (mean +/- SD): RA mean pressure 7+/-5 mm Hg, pulmonary artery mean
      pressure 28+/-10, pulmonary capillary wedge pressure 21+/-8 mm Hg, and cardiac
      index 2.9+/-1.4 (L/min/m2), respectively. Plasma ANP levels were significantly
      elevated at 162+/-117 (normal range 20 to 65 pg/ml, p < 0.05), as were LA and RA
      volumes compared with healthy controls (RA volume 128+/-64 ml vs 82+/-25 ml, p <
      0.05; LA volume 157+/-54 ml vs 71+/-24 ml, p < 0.01, respectively). ANP showed a
      stronger relation with atrial volumes (RA volume, r = 0.91, p = 0.0001; LA
      volume, r = 0.80, p = 0.001) than with atrial pressures (RA mean pressure, r =
      0.45, p = 0.03; pulmonary capillary wedge pressure, r = 0.67, p = 0.001). A
      subgroup analysis of patients with increased RA or LA volumes (>1 SD of mean of
      controls) revealed a stronger relation between ANP and RA volumes than between
      ANP and LA volumes. CONCLUSIONS: These data suggest that increased right heart
      volume with subsequent increased atrial stretch is the major determinant for ANP
      release in patients with stable CHF.

PMID- 9539473
TI  - Beneficial effects of 1-year captopril therapy in children with chronic aortic
      regurgitation who have no symptoms.
AB  - OBJECTIVE: This prospective study was performed to assess the effects of 1 year
      of angiotensin-converting enzyme inhibition with captopril in 20 children (mean
      age 14.3+/-2.3 years) with asymptomatic chronic aortic regurgitation. METHODS AND
      RESULTS: At 12 months patients receiving captopril had a significant reduction in
      left ventricular end-diastolic and end-systolic dimensions (57+/-9.3 vs 51+/-9.5
      mm, p < 0.001; 35.4+/-6.1 vs 32+/-6.8 mm, p < 0.001), end-diastolic and end
      systolic volume indexes (111+/-36 vs 94+/-29 ml/m2, p < 0.001; 35+/-13 vs 30+/-12
      ml/m2, p < 0.001, respectively), and mass index (138+/-37 vs 109+/-32 gm/m2, p <
      0.0001) determined by two-dimensional echocardiography. Meridian (p < 0.01) and
      circumferential (p < 0.0001) wall stresses also decreased significantly with
      therapy. Significant reduction (27.8%, p < 0.0001) was achieved in regurgitant
      fraction with captopril. CONCLUSIONS: These data show that the long-term therapy
      with angiotensin-converting enzyme inhibitors is able to reverse left ventricular
      dilation and hypertrophy and suggest that such therapy has the potential to
      favorably influence the natural history of the disease in children.

PMID- 9539475
TI  - Rapid onset and dissipation of left atrial spontaneous echo contrast during
      percutaneous balloon mitral valvotomy.
AB  - BACKGROUND: Thromboembolism after percutaneous balloon mitral valvotomy (PBMV)
      has been attributed to dislodement of preexisting thrombus during transseptal
      puncture and instrumentation of the left atrium. The occurrence of thromboembolic
      events after PBMV in the absence of demonstrable left atrial thrombus before PBMV
      suggests that thrombus might form during the procedure. Spontaneous echo contrast
      (SEC) is a swirling pattern of blood echogenicity that is a marker of blood
      stasis in the left atrium. Exacerbation of left atrial SEC during PBMV may be
      indicative of an increased thromboembolic risk. METHODS: Transesophageal
      echocardiography was performed during PBMV in 20 patients with mitral stenosis.
      Grades of severity of left atrial SEC [0 (nil) to 4+ (severe)] were allocated
      before and after each balloon inflation. RESULTS: Before PBMV, SEC was present in
      17 patients. New SEC or increased severity of SEC was observed during 49 of 56
      balloon inflations. SEC was unchanged after six deflations, decreased after 14
      deflations, and disappeared after 36 deflations. The mean times to onset and
      dissipation of SEC after balloon inflation and deflation were 3.1+/-1.5 and 3.9+/
      1.6 seconds, respectively. After successful PBMV, SEC was unchanged in three
      patients, decreased in one, and resolved in 13. CONCLUSIONS: SEC is a dynamic and
      acutely reversible phenomenon that is highly sensitive to changes in left atrial
      hemodynamic conditions. Left atrial blood stasis induced by balloon inflation may
      promote thrombogenesis during PBMV.

PMID- 9539474
TI  - Aortic stiffness in young patients with heterozygous familial
      hypercholesterolemia.
AB  - BACKGROUND: Dyslipidemia is a primary risk factor for the development of
      atherosclerosis. Aortic distensibility is an important determinant of left
      ventricular function and coronary blood flow whose possible alterations in
      patients with dyslipidemia have not been fully investigated. METHODS: To assess
      the effect of dyslipidemia on the elastic properties of the aorta, we studied 60
      patients (mean age 37+/-11 years) with heterozygous familial hypercholesterolemia
      and no manifest arterial disease and compared them with 20 of their
      normolipidemic siblings (mean age 34+/-10 years). Two indexes of the aortic
      elastic properties were measured: aortic distensibility was calculated by use of
      the formula: 2 x (AoS-AoD)/PP x AoD, and aortic stiffness index was calculated by
      use of the formula: In (SBP/DBP)/(AoS-AoD)/AoD, where AoS and AoD are aortic root
      end-systolic and end-diastolic diameters, respectively, SBP and DBP are systolic
      and diastolic arterial pressure, respectively, and PP is pulse pressure. Internal
      aortic root diameters were measured at 3 cm above the aortic valve by use of two
      dimensional guided M-mode transthoracic echocardiography, and arterial pressure
      was measured simultaneously at the brachial artery by sphygmomanometry. RESULTS:
      The mean aortic systolic and diastolic diameter index did not differ
      significantly between the two groups. In contrast, aortic distensibility was
      found to be significantly reduced in subjects with isolated familial
      hypercholesterolemia compared with that in the control group (2.15+/-1.72
      cm2.dynes(-1).10(-6) vs 3.18+/-1.58 cm2.dynes(-1).10(-6), p < 0.02). In addition,
      the mean aortic stiffness index was double in patients with familial
      hypercholesterolemia compared with that in normolipidemic subjects. CONCLUSIONS:
      Severe dyslipidemia does not overtly influence aortic dimensions but leads to
      impairment of aortic elastic properties before the occurrence of clinical
      manifestations of atherosclerotic disease.

PMID- 9539476
TI  - Reduced pulmonary clearance of endothelin-1 in pulmonary hypertension.
AB  - OBJECTIVE: Pulmonary hypertension (PHT) is associated with increased endothelin-1
      (ET-1) levels that correlate with the severity of the disease. The pulmonary
      circulation is an important site for ET-1 metabolism and may modulate plasma ET-1
      through an increase in production, a reduction in removal, or a combination of
      both. We measured and compared pulmonary metabolism of circulating ET-1 in
      controls and in patients with PHT. METHODS AND RESULTS: The indicator-dilution
      technique was combined with measurements of ET-1 levels to quantify pulmonary
      metabolism of ET-1 in controls (n = 13) and in patients with PHT (n = 17). ET-1
      levels doubled in PHT (p < 0.05) and, although there was no difference between
      aortic and pulmonary artery levels in controls (0.68+/-0.09 and 0.61+/-0.08
      pg/ml, respectively, p = 0.22), they tended to be higher in PHT (1.23+/-0.26 vs
      1.07+/-0.19 pg/ml, p = 0.08). Pulmonary extraction of tracer iodine-125-ET-1 was
      reduced from 47%+/-2.0% in the controls to 34%+/-3.6% in PHT (p = 0.005) and
      inversely correlated with the severity of pulmonary hypertension (r = -0.524, p =
      0.03). Consequently, circulating ET-1 clearance was reduced by PHT from 1424+/-77
      ml/min to 892+/-119 ml/min (p < 0.001). Pulmonary production of circulating ET-1
      (in picograms per minute) was not different but the quantity of ET-1 that
      survives passage through the lungs was increased by PHT (1860+/-359 pg/min vs
      992+/-152 pg/min, p = 0.037). CONCLUSION: PHT is associated with a reduced
      pulmonary clearance of ET-1 that contributes to the increase in circulating
      levels.

PMID- 9539478
TI  - Mechanism of luminal narrowing in cardiac allograft vasculopathy: inadequate
      vascular remodeling rather than intimal hyperplasia is the major predictor of
      coronary artery stenosis. Working Group on Cardiac Allograft Vasculopathy.
AB  - BACKGROUND: Despite increasing knowledge about degree and distribution pattern of
      intimal hyperplasia in cardiac allograft vasculopathy, coronary artery remodeling
      is only poorly understood in this disease. METHODS: To evaluate vascular
      geometry, intravascular ultrasound was used to characterize 57 advanced lesions
      in 35 consecutive transplant recipients. Lumen, plaque, and vessel area in these
      target lesions were compared with proximal and distal reference sites. RESULTS
      AND CONCLUSIONS: Vascular remodeling by compensatory local vessel enlargement
      (positive remodeling) and circumscript vascular constriction (negative
      remodeling) could be demonstrated. Plaque area in stenotic lesions was
      significantly increased compared with the mean reference site (5.6+/-3.0 mm2
      versus 2.8+/-1.5 mm2, p < 0.001); however, inadequate compensatory enlargement
      rather than intimal hyperplasia was shown to be the most important predictor of
      luminal obstruction (r = 0.77, p < 0.001).

PMID- 9539477
TI  - Safety and optimal dose of intracoronary adenosine 5'-triphosphate for the
      measurement of coronary flow reserve.
AB  - BACKGROUND: Adenosine 5'-triphosphate (ATP) has been demonstrated to have similar
      vasodilator potency and fewer hemodynamic or electrocardiographic derangements
      compared with papaverine in the measurement of coronary flow reserve. However,
      there is little data about its optimal dose and the effect on myocardial lactate
      metabolism. METHODS: Under continuous monitoring of the left anterior descending
      coronary flow velocity with a Doppler guide wire, we investigated the changes of
      hemodynamics, electrocardiogram, and myocardial lactate metabolism before and
      after the administration of 50 microg ATP and 10 mg papaverine into the left
      coronary artery in 18 patients with normal coronary arteries. To determine the
      optimal dose of ATP for the coronary flow reserve in the left coronary artery, we
      measured coronary flow velocity with five incremental doses of intracoronary ATP
      (0.5, 5, 15, 30, and 50 microg) and 10 mg of papaverine in another seven
      patients. RESULTS: In contrast to papaverine, ATP did not produce any significant
      changes in hemodynamics or the electrocardiogram. The increase in the coronary
      flow velocity of the two agents was similar. Although all patients showed lactate
      production after the administration of papaverine, only three patients showed
      lactate production after ATP (p < 0.001). The coronary flow reserve derived from
      > or = 215 microg of ATP was similar to that derived from papaverine. There was a
      significant correlation between the coronary flow reserve obtained with > or = 5
      microg of ATP and that obtained with papaverine. CONCLUSIONS: These results
      suggest that maximal coronary vasodilation in the left coronary artery can be
      safely obtained with doses > or = 15 microg of intracoronary ATP in patients with
      normal coronary arteries.

PMID- 9539479
TI  - Role of transesophageal echocardiography in the evaluation of patients with
      clinical pacemaker syndrome.
AB  - OBJECTIVES: The goal of this study was to investigate the possible role of
      transesophageal echocardiography in the evaluation of patients with clinical
      pacemaker syndrome. BACKGROUND: Several reports on transthoracic
      echocardiographic features of ventricular pacing were described; however, no
      previous study of transesophageal echocardiography has been undertaken in
      patients at the severe end of pacemaker syndrome who need reprogramming of dual
      chamber pacing for symptom relief. METHODS: Twelve patients with ventricular
      inhibited pacemakers (VVI) with clinical symptomatic pacemaker syndrome (group I)
      and 10 patients with VVI without pacemaker syndrome (group II) were prospectively
      studied. The two groups were pacemaker dependent and had persistent
      ventriculoatrial conduction. Transesophageal echocardiographic parameters were
      assessed in group II and within 6 hours before reprogramming to the DDD mode in
      group I. Follow-up transesophageal echocardiographic study was performed 28+/-5
      days after reprogramming in group I. RESULTS: All patients in group I had
      subjective improvements of symptoms after DDD reprogramming. The atrial reverse
      flow velocities of pulmonary veins in group I before reprogramming were
      significantly higher in group II (39.3+/-11.4 versus 15.7+/-13.5 cm/sec, p <
      0.0001). Spontaneous echo contrast in the descending aorta was detected in all
      patients from group I before reprogramming. The prevalence of significant mitral
      regurgitation (> or = moderate) was significantly higher in group I before
      reprogramming than in group II (67% versus 8%, p = 0.01). Significant mitral
      regurgitation and spontaneous echo contrast in the descending aorta in group I
      disappeared after reprogramming to the DDD mode. CONCLUSIONS: Transesophageal
      echocardiography provides physiologic, pacemaker-related hemodynamic changes in
      paced patients. Significantly higher atrial reverse flow velocities of pulmonary
      veins, increased frequency of spontaneous echo contrast in the descending aorta,
      and significant mitral regurgitation are peculiar echocardiographic findings in
      patients with VVI with clinical pacemaker syndrome.

PMID- 9539480
TI  - Mitral inflow and pulmonary venous Doppler measurements do not predict pulmonary
      capillary wedge pressure in heart transplant recipients.
AB  - BACKGROUND: Noninvasive estimation of pulmonary capillary wedge pressure (PCWP)
      with Doppler-derived mitral inflow pattern has been shown to correlate well with
      invasively measured PCWP; however, it has not yet been determined whether Doppler
      derived mitral inflow pattern can be used to estimate PCWP accurately in heart
      transplant recipients. METHODS: To determine if mitral and pulmonary venous
      inflow data can be applied to calculate PCWP in heart transplant recipients, some
      day echocardiograms and right heart catheterizations were reviewed and 83
      echocardiograms with adequate mitral inflow patterns in 53 patients were studied.
      Twenty-eight studies that also had adequate pulmonary venous inflow patterns were
      selected for offline analysis. RESULTS: Using a previously published formula
      [PCWP = 17 + (5.3 x E/A) - (0.11 x IVRT)], where E/A is the ratio of early to
      late mitral inflow velocities and IVRT is the isovolumic relaxation time, we
      derived a calculated PCWP, the results of which compared poorly with the measured
      PCWP (r = 0.33; p = 0.002). Linear regression analysis of measured PCWP versus
      mitral inflow Doppler flow velocity parameters also revealed poor to modest
      correlation. Adding parameters derived from the pulmonary venous inflow patterns
      failed to improve this correlation. CONCLUSION: Doppler-derived estimation of
      PCWP with mitral and pulmonary venous inflow patterns cannot be used to reliably
      predict PCWP in heart transplant recipients.

PMID- 9539481
TI  - Effects of adenosine on left ventricular filling dynamics in patients with and
      without coronary artery disease: a Doppler echocardiographic study.
AB  - OBJECTIVES: Adenosine, a potent coronary vasodilator is used as a pharmacologic
      stress agent for the assessment of coronary artery disease. A paucity of data
      exists on its effects on filling dynamics. Accordingly, this study was undertaken
      to evaluate the effects of adenosine on left ventricular filling as assessed by
      Doppler echocardiography. METHODS AND RESULTS: We studied 69 patients (45 men, 24
      women, aged 61+/-11 years) referred for evaluation of coronary artery disease.
      Two-dimensional echocardiography and pulsed-Doppler recordings at the mitral
      valve tips and annulus were performed at baseline and at maximal adenosine
      infusion of 140 microg/kg/min. During adenosine infusion, an increase in heart
      rate occurred (70+/-14 beats/min to 85+/-16 beats/min), with a mild decrease in
      blood pressure (130/75+/-26/13 mm Hg vs 119/66+/-25/13 mm Hg); both p < 0.02.
      Changes in filling dynamics included an increase in peak early inflow velocity,
      E/A ratio, and normalized peak filling rate. Of the patients investigated, 23 had
      one-vessel coronary artery disease, 29 had coronary disease in two vessels or
      more by angiography, and 17 had no significant disease. Patients without coronary
      artery disease (controls) had mild changes in E/A ratio (mean 7%). Patients with
      coronary artery disease had a more heterogeneous change in filling dynamics
      (range 43% to 369%, mean 26%), with a significant overlap with controls. However,
      changes in E/A ratio during adenosine infusion that exceeded the confidence
      limits of normal (-20% to +30%) were specific for coronary artery disease, with a
      positive predictive value of 84%. CONCLUSIONS: Normally, adenosine induces
      significant increases in early filling as assessed by Doppler. The changes in
      patients with coronary stenosis are more variable. When these changes fall
      outside the confidence limits of normal, they are predictive of coronary artery
      disease.

PMID- 9539483
TI  - Prognostic value of exercise thallium-201 imaging in a community population.
AB  - BACKGROUND: The prognostic value of exercise thallium-201 imaging has been well
      established in referral patient populations at tertiary care centers, but these
      results may be influenced by referral bias. METHODS: This study was performed to
      evaluate the prognostic value of thallium imaging in a community-based population
      of 446 residents of Olmsted County, Minn. Eleven variables were prospectively
      selected and tested for their associations with outcome end points. RESULTS: Four
      variables (age, history of myocardial infarction, number of abnormal thallium
      segments on the postexercise images, and increased thallium lung uptake)
      contained the most independent prognostic information. For the end point overall
      mortality rate, the multivariate chi-square values were 17.2 (p < 0.0001) for age
      and 20.9 (p < 0.0001) for the number of abnormal thallium segments on the
      postexercise images. Five-year survival rate for patients older than the median
      age of 59 years with an abnormal scan was 84% versus 97% for patients < or = 59
      years of age with a normal scan. CONCLUSION: Exercise thallium imaging was useful
      for prognostic purposes in this relatively low-risk community population,
      confirming the findings of referral population studies.

PMID- 9539482
TI  - Assessment of coronary artery disease in women by dobutamine stress
      echocardiography: comparison with stress thallium-201 single-photon emission
      computed tomography and exercise electrocardiography.
AB  - BACKGROUND: Dobutamine stress echocardiography (DSE) is sensitive and specific in
      detecting myocardial ischemia of male patients. However, there have been few
      reports about the use of DSE for the detection of coronary artery disease (CAD)
      in women. METHODS: DSE was evaluated in 51 consecutive women who underwent
      concomitant quantitative coronary angiography. Forty-four of the 51 patients
      received stress thallium-201 single-photon emission computed tomography (SPECT),
      and 30 of the 51 patients had interpretable results (exercise level > or = 85% of
      age-predicted maximal heart rate) of treadmill exercise. Twenty-nine patients had
      angiographically documented CAD defined as > or = 50% diameter stenosis. RESULTS:
      The overall sensitivity of DSE and stress 201Tl SPECT in detecting CAD was 93%
      and 79% (p = nonsignificant), and the specificity was 82% and 75% (p =
      nonsignificant), respectively. A combination of both tests increased the
      sensitivity (96%) at the expense of some decrease in specificity (60%). The
      agreement of DSE and 201Tl SPECT was 68% (30 of 44; kappa statistic = 0.35; p <
      0.0001). The overall sensitivity, specificity, and accuracy in detecting CAD by
      treadmill exercise test and DSE were 71% vs 93% (p = nonsignificant), 44% vs 82%
      (p = 0.036), and 57% vs 88% (p = 0.003). In patients with abnormal results of
      treadmill exercise testing, the false-positive rate in detecting CAD was 2 (18%)
      of 11 in patients with abnormal results of DSE and 7 (88%) of 8 in those with
      normal results of DSE (p = 0.005). In patients with normal results of treadmill
      exercise testing, the false-negative rate in detecting CAD was 4 (100%) of 4 in
      patients with abnormal results of DSE and 0 (0%) of 7 in those with normal
      results of DSE (p = 0.003). CONCLUSION: The diagnostic accuracy of DSE was
      similar to that of stress 201Tl SPECT in women. DSE was able to stratify female
      patients with either abnormal or normal results of treadmill exercise testing and
      to avoid unnecessary cardiac catheterization.

PMID- 9539484
TI  - Head-up tilt testing potentiated with low-dose sublingual isosorbide dinitrate: a
      simplified time-saving approach for the evaluation of unexplained syncope.
AB  - BACKGROUND: Head-up tilt testing is widely used in the clinical assessment of
      patients with unexplained syncope. However, the lack of a standard methodology
      and the conflicting results concerning sensitivity and specificity of the
      procedure have prompted further studies to define a more cost-effective approach
      for tilt testing. OBJECTIVES: Our clinical investigation was undertaken to assess
      the diagnostic value in unexplained syncope of a simple and time-saving protocol
      for head-up tilt testing, including low-dose sublingual isosorbide dinitrate
      administration. PATIENTS AND METHODS: A group of 73 consecutive patients (43
      women and 30 men, mean age 39.6+/-21.8 years) with unexplained syncope despite
      conventional clinical cardiovascular and neurologic assessment and 10
      asymptomatic control subjects underwent head-up tilt testing with isosorbide
      dinitrate challenge. Participants were tilted at 60 degrees for 30 minutes
      without medication; if no symptoms occurred, 1.25 mg of isosorbide dinitrate was
      administered sublingually and tilting was continued for an additional 15 minutes.
      RESULTS: During the drug-free phase of the test 14 (19.2%) patients had syncope.
      After isosorbide dinitrate administration syncope occurred in another 28 patients
      (38.3%); minor symptoms in association with hypotension developed in 10 (13.7%)
      patients. The test result was negative in all control subjects. The positive rate
      and specificity of head-up tilt testing with isosorbide dinitrate provocation
      were 57.5% and 100%, respectively. CONCLUSIONS: This new practical diagnostic
      procedure was found to be fairly sensitive and clearly specific in inducing a
      vasovagal reflex in patients with syncope of uncertain origin. Consequently, such
      approach could give a significant contribution in the diagnostic workup of these
      patients.

PMID- 9539485
TI  - Excellent reliability of nurse-based bedside diagnosis of acute myocardial
      infarction by rapid dry-strip creatine kinase MB, myoglobin, and troponin T.
AB  - With the aim to compare the diagnostic efficacy as regards acute myocardial
      infarction of two rapid dry-strip tests, one with both creatine kinase MB (CK-MB)
      and myoglobin (C + M) and the other with troponin T, and to test the reliability
      of bedside diagnosis by the coronary care unit (CCU) nurse, 151 patients with
      acute chest pain admitted to the CCU were investigated. There was no difference
      in diagnostic performance between rapid tests and quantitative determinations.
      With <6-hour duration of symptoms, the sensitivity was better for C + M than for
      troponin T (72% vs 33%, p < 0.05). With symptoms lasting >12 hours on arrival,
      troponin T performed better, with 100% sensitivity and a negative predictive
      value of 100% in the 6-hour retest. For exclusion of damage, the two tests have
      similar and reliable diagnostic capacities 12 hours after the onset of symptoms.
      The bedside diagnosis or exclusion of acute myocardial infarction was carried out
      rapidly (within 20 minutes) and reliably by the CCU nurses.

PMID- 9539486
TI  - Plasma endothelin-1 levels in patients with angina pectoris and normal coronary
      angiograms.
AB  - BACKGROUND: Some patients with typical angina and electrocardiographic evidence
      of ischemia have normal coronary angiograms. These patients have a reduced
      coronary flow reserve and abnormal endothelium-dependent vasodilator responses;
      this syndrome is known as microvascular angina. Among endothelium-derived
      peptides, endothelin-1 (ET-1) is a potent vasoconstrictor and an important
      modulator of microvascular function. METHODS: Plasma ET-1 was measured in 13
      patients with typical angina, instrumental evidence of ischemia, and normal
      arteriograms and in 20 normal control subjects. RESULTS: Mean concentration of ET
      1 was 2.89+/-1.24 pmol/L in patients with angina and normal angiograms and 1.99+/
      0.81 pmol/L in normal control subjects (p < 0.02). Plasma levels of ET-1 values
      were significantly higher in patients with angina, positive exercise test results
      for ischemia, and normal coronary arteriograms compared with the group of
      patients with no clinical or instrumental evidence of ischemia. CONCLUSIONS: This
      is consistent with the hypothesis that in patients with microvascular angina, an
      endothelial dysfunction in the coronary vascular area caused by impaired
      endothelium-derived ET-1 could play an active role in the disease process.

PMID- 9539487
TI  - ST-segment elevation in right precordial leads implies depressed right
      ventricular function after acute inferior myocardial infarction.
AB  - BACKGROUND: The prognosis of acute inferior myocardial infarction is worse when
      it is complicated by right ventricular infarction. ST elevation in the right
      precordial leads is one of the reliable methods for detecting acute right
      ventricular infarction. The purpose of the study was to examine the relation
      between ST elevation in the right precordial electrocardiographic leads during
      acute inferior infarction and the severity of right ventricular systolic
      dysfunction. METHODS: This study analyzed the relation between ST elevation > or
      = 0.1 mV in V4R and the severity of right ventricular systolic dysfunction in 43
      consecutive patients (men/women: 35/8; average age 62+/-9 years) with acute
      inferior myocardial infarction with a rapid-response Swan-Ganz catheter to
      measure the right ventricular ejection fraction (RVEF). RESULTS: RVEF was
      significantly lower in patients with ST elevation (n = 18) than in those without
      (n = 25) (33%+/-6% vs 40%+/-9%, p = 0.010). If the infarct-related lesion was
      located in the proximal right coronary artery, RVEF tended to be lower than if
      the lesion was located in the distal right coronary artery or the left circumflex
      coronary artery (33%+/-10% vs 37%+/-9% vs 42%+/-9%, p = 0.101). Logistic
      regression analysis demonstrated that ST elevation in V4R was the only
      independent predictor of depressed RVEF (odds ratio = 5.31, 95% confidence
      interval = 1.28 to 22.1, p = 0.022). CONCLUSION: ST elevation in lead V4R during
      acute inferior myocardial infarction predicts right ventricular systolic
      dysfunction.

PMID- 9539488
TI  - Coronary calcium and standard risk factors in symptomatic patients referred for
      coronary angiography.
AB  - OBJECTIVES: The purpose of this study was to compare quantitative estimates of
      coronary calcification with traditional coronary risk factors to determine their
      independent predictive power for the diagnosis of obstructive angiographic
      coronary artery disease in symptomatic patients. METHODS: Three hundred sixty
      eight symptomatic patients underwent coronary angiography and electron beam
      computed tomography at four different centers between April 1989 and December
      1993. A blinded cardiologist interpreted the electron beam computed tomograms.
      Coronary risk factors were obtained in all 368 patients. Both bivariate and
      multivariate analyses were used to investigate the relation between risk factors
      and angiographic disease. RESULTS: One hundred fifty-eight patients (43%) had
      angiographically obstructive coronary artery disease (>50% luminal stenosis) and
      297 (81%) had coronary calcification. At the bivariate level, only male sex and
      log-transformed coronary calcification were predictive of angiographic disease (p
      = 0.008, p = 0.001). By multivariate analysis, only male sex and coronary
      calcification were predictive (p = 0.001, p = 0.001). Sixty-four of the 71
      patients without coronary calcification did not have disease, yielding a negative
      predictive value of 90%. Receiver operating characteristic curve analysis showed
      that the amount of coronary calcium was a significantly better discriminator of
      disease than were the other risk factors. CONCLUSIONS: Coronary calcification is
      a stronger predictor of angiographic coronary artery disease in symptomatic
      patients undergoing angiography than are standard risk factors.

PMID- 9539489
TI  - Differential restenosis rate of individual coronary artery sites after
      multivessel angioplasty: implications for revascularization strategy. CABRI
      Investigators. Coronary Angioplasty versus Bypass Revascularisation
      Investigation.
AB  - BACKGROUND: Restenosis is a major limitation of angioplasty. In this analysis we
      assessed the effects of lesion site and quality of dilatation on restenosis rate
      in the Coronary Angioplasty versus Bypass Revascularization Investigation
      population who underwent angioplasty. METHODS: The angiographic quality of the
      successful angioplasty revascularization at each site was assessed, and the
      subsequent restenosis rate was determined. Restenosis was defined by the need for
      a second angioplasty at the initial site or by surgical coronary bypass grafting
      at or distal to the initial site. RESULTS: The restenosis rate was unaffected by
      quality of dilatation but was significantly more common in the proximal left
      anterior descending artery compared with other sites, whether or not optimal
      dilatation had been achieved (relative risk 2.0 and 1.9, respectively).
      CONCLUSION: Revascularization strategies in multivessel disease should consider
      the presence or absence of a proximal left anterior descending artery target.
      Furthermore in studies in which restenosis is an outcome of interest, an
      allowance should be made for the distribution of target disease.

PMID- 9539490
TI  - Influence of gradually increased slow balloon inflation on restenosis after
      coronary angioplasty.
AB  - BACKGROUND: Balloon inflation during coronary angioplasty results in shear stress
      induced vessel wall injury with development of restenosis. This randomized trial
      compared the impact of two different balloon inflation strategies (slow versus
      fast) on restenosis after coronary angioplasty. METHODS: Two hundred seven
      patients were randomized to undergo either fast or gradually increased slow
      inflation after successful placement of the balloon catheter inside the target
      lesion. One hundred six underwent fast, and 101 underwent gradually increased
      slow balloon inflation. Coronary angiograms were quantitatively analyzed before
      angioplasty, after angioplasty, and at follow-up 5.9+/-1.6 months after the
      initial procedure. RESULTS: Both groups had an identical primary success rate
      (98.1% vs 98%; p = 0.96) and a similar minimal luminal diameter before (0.49+/
      0.26 mm vs 0.48+/-0.22 mm; p = 0.8) and after (2.22+/-0.97 mm vs 2.26+/-0.66 mm;
      p = 0.7) angioplasty. Slow balloon inflation did not reduce late luminal loss
      (0.58+/-0.77 mm vs 0.74+/-0.87 mm; p = 0.2), net gain (1.33+/-0.84 mm vs 1.19+/
      0.81 mm; p = 0.3), or minimal luminal diameter at follow-up (1.80+/-0.97 mm vs
      1.72+/-1.0 mm; p = 0.6) significantly. Restenosis, defined as >50% diameter
      stenosis at follow-up, occurred in 24% in the slow inflation group versus 36% in
      the fast inflation group (p = 0.09). Clinical events during 6-month follow-up
      were similar in both groups (repeat angioplasty, fast 5.6%, slow 4.8%, p = 0.8;
      nonfatal myocardial infarction, fast 2.2%, slow 1.2%, p = 0.6; death, fast 1.1%,
      slow 0%, p = 0.3). CONCLUSION: The present randomized trial of two different
      balloon inflation strategies shows no statistically significant difference in net
      gain, minimal luminal diameter, or restenosis after coronary angioplasty. The
      difference in net gain, minimal luminal diameter, and restenosis rate were not
      statistically significant, but may represent a trend toward a reduction of smooth
      muscle cell proliferation and intimal hyperplasia induced by careful dilation of
      the stenotic lesion with gradually increased slow balloon inflation and reduction
      of shear stress-related vessel wall injury.

PMID- 9539492
TI  - Advantage of stents in the most proximal left anterior descending coronary
      artery.
AB  - OBJECTIVES: Balloon angioplasty of the proximal left anterior descending artery
      is associated with a high rate of restenosis. We hypothesized that the
      significant reduction in restenosis rates demonstrated by stent implantation in
      the coronary arteries in general would be especially prominent in the most
      proximal left anterior descending coronary artery. METHODS: We reviewed 65
      consecutive patients in whom stents were placed in the most proximal left
      anterior descending artery between March 1990 and July 1995 and compared them
      with 56 consecutive patients with angioplasty. Minimum luminal diameter was
      measured angiographically before, after, and 6 months after the intervention. We
      compared the change in minimum luminal diameter and restenosis rate between the
      patients with stents and the patients with angioplasty to clarify the response of
      this important artery to these different procedures. RESULTS: There was 6-month
      angiographic follow-up of the treated lesion in 99% of the patients. The
      postprocedure minimum luminal diameter, acute gain, and minimum luminal diameter
      at follow-up were greater in arteries treated with stents than in those treated
      with balloons. Of importance, late loss was not significantly different between
      the two groups after treatment at this site. Thus the restenosis rate after
      angioplasty was 52% compared with 20% after stent implantation (p < 0.001).
      CONCLUSIONS: Stent implantation in the most proximal left anterior descending
      artery is associated with an even greater reduction in restenosis rate than
      implantations elsewhere in the coronary arteries. This enhanced reduction in
      restenosis appears to be due to an unusually large amount of late loss after
      angioplasty at this site.

PMID- 9539491
TI  - Late clinical and angiographic follow-up after stenting in evolving and recent
      myocardial infarction.
AB  - OBJECTIVES: This study sought to assess the late clinical and angiographic
      outcomes of patients who received stents within the first week of acute
      myocardial infarction (AMI). BACKGROUND: Recent studies have demonstrated that
      stenting of the infarct-related artery is a useful adjunct to balloon angioplasty
      in patients with AMI. However, there are limited data on the late clinical and
      angiographic outcomes of these patients. METHODS: Between January 1994 and
      September 1995, 32 patients at our institution underwent stenting of the infarct
      related artery within 1 week of AMI: 13 within 14 hours (evolving group) and 19
      between days 2 and 7 (recent AMI group). Late clinical follow-up was obtained on
      all survivors. Quantitative angiographic measurements were recorded on the
      stented segments before stenting, immediately after stenting, and on the follow
      up angiograms. RESULTS: At 13.1+/-6.4 months from the time of stenting, three
      patients died and three required repeat angioplasty, but no patient had
      reinfarction or required bypass surgery. At follow-up 26 (81%) of 32 patients
      remained free of major cardiac events; of these, 24 (92%) were free of angina.
      Repeat angiography performed at 10.8+/-7.5 months in 26 (87%) of 30 discharged
      patients showed that all infarct-related arteries were patent and the restenosis
      rate was low: 22% in the 13 patients with evolving AMI (<14 hours) and 12% in the
      19 patients with recent AMI (days 2 through 7). CONCLUSION: In this study
      stenting of the infarct-related artery in patients with evolving and recent AMI
      was associated with a favorable late clinical outcome. Patency of the infarct
      related artery was well maintained, and the restenosis rate was low.

PMID- 9539493
TI  - Mechanical recanalization of total coronary occlusions with the use of a new
      guide wire.
AB  - The mechanical approach in the recanalization of total coronary occlusions
      consisted of the use of a new 0.014-inch standard coronary guide wire with
      jointless spring coil design that improves steering characteristics and tip
      stiffness. In addition, a 0.014-inch soft tip wire with hydrophilic coating and
      low-profile 1.5 mm over-the-wire balloons were used. The first wire was used
      selectively in 86 patients to treat 95 total occlusions, of which 51 (54%) were
      older than 3 months. Unfavorable angiographic characteristics were present in 79
      (83%) of 95 lesions. Overall crossing success was 71% (67 of 95 lesions).
      Complications were one coronary perforation with cardiac tamponade necessitating
      emergency bypass surgery. In conclusion, the mechanical approach with the use of
      the standard coronary guide wire with jointless spring coil design provides a
      high success rate in the recanalization of unfavorable total occlusions.

PMID- 9539494
TI  - Fundamentals of coagulation and glycoprotein IIb/IIIa receptor inhibition.
AB  - An understanding of the coagulation process and the role of platelets is
      essential to recognizing the shortcomings of older anticoagulant therapies and
      appreciating the clinical potential of newer forms of antiplatelet and
      anticoagulant therapy for acute coronary syndromes. The anticoagulant actions of
      heparin are severely limited by dependence on antithrombin III, neutralization by
      platelet factor 4, and the resistance of clot-bound thrombin and platelet
      membrane-bound factor Xa to the heparin-antithrombin III complex. Unlike heparin,
      the direct thrombin inhibitors (such as hirudin) are active against both
      circulating and clot-bound thrombin. However, in recent clinical trials they have
      not resulted in major improvements in patient outcome. Another new class of
      drugs, the glycoprotein IIb/IIIa receptor antagonists, blocks the final common
      pathway of platelet aggregation and is capable of preventing platelet
      accumulation at sites of injury. The net effect is a dramatic reduction in the
      amount of platelet membrane available to support the process of coagulation.
      Clinical trials with the glycoprotein IIb/IIIa inhibitors have suggested that
      this class of agents may be particularly effective in reducing the thrombotic
      complications associated with coronary interventional procedures and may be
      useful in the treatment of acute coronary syndromes.

PMID- 9539496
TI  - Rationale and clinical evidence for the use of GP IIb/IIIa inhibitors in acute
      coronary syndromes.
AB  - Platelet glycoprotein (GP) IIb/IIIa blockade has the potential to advance
      treatment of acute coronary syndromes, both as a primary pharmacologic approach
      and an adjunct to interventional treatment strategies. The benefits of GP
      IIb/IIIa inhibition with the chimeric monoclonal antibody abciximab in preventing
      ischemic complications of interventional treatment have been well defined in
      patients with unstable angina. In the future, major therapeutic applications for
      this class of agents may include the stabilization of patients with unstable
      angina and potentially as single medical therapy, as several recently completed
      trials have suggested. Evidence also is accumulating on the use of GP IIb/IIIa
      blockade as adjunctive therapy in fibrinolytic approaches to treatment of acute
      myocardial infarction. Several ongoing trials are evaluating the safety and
      efficacy of this novel strategy. This article reflects a distillation of the
      views and consensus regarding the prospective use of GP IIb/IIIa inhibitors in
      patients with acute coronary syndromes expressed by a group of international
      experts convened in Davos, Switzerland, February 16, 1997. This report attempts
      to review clinical progress to date, formulate recommendations, and map out
      potentially fruitful lines of inquiry for future investigation.

PMID- 9539495
TI  - An overview of the results of clinical trials with glycoprotein IIb/IIIa
      inhibitors.
AB  - The era of platelet glycoprotein (GP) IIb/IIIa receptor inhibition in cardiology
      was inaugurated in 1994 with the publication of the Evaluation of 7E3 for the
      Prevention of Ischemic Complications (EPIC) trial results. EPIC demonstrated that
      the GP IIb/IIIa blocker abciximab, administered as a bolus and 12-hour infusion,
      afforded protection against ischemic complications in high-risk patients
      undergoing angioplasty and atherectomy, including those with unstable angina or
      evolving myocardial infarction (MI). A significant reduction in the incidence of
      death, acute MI, or revascularization was apparent at 30 days and also sustained
      at 6-month and 3-year follow-up. The subsequent Evaluation in PTCA to Improve
      Long-Term Outcome with Abciximab GP IIb/IIIa Blockade (EPILOG) study extended
      these findings to the full spectrum of coronary intervention patients, confirming
      that abciximab provided similar benefits in low-risk patients as well. The EPILOG
      trial also proved that any excess bleeding risk associated with potent
      antiplatelet therapy could be brought down to placebo levels through the use of a
      low-dose, weight-adjusted heparin regimen, early vascular sheath removal, and
      elimination of routine postprocedural heparinization. The potential for an
      advantage of GP IIb/IIIa blockade in patients with refractory unstable angina/non
      Q-wave MI was demonstrated in the c7E3 Fab Antiplatelet Therapy in Unstable
      Refractory Angina (CAPTURE) trial, which showed that a 24-hour preprocedural
      abciximab infusion effectively stabilized these patients, thereby enhancing the
      safety of intervention and reducing the 30-day incidence of ischemic events. A
      similar pattern of benefit has emerged from clinical trials of such other GP
      IIb/IIIa inhibitors as eptifibatide, lamifiban, and tirofiban. Trials are
      currently underway to clarify the benefits of GP IIb/IIIa blockers in patients
      undergoing stenting and as an adjunct to thrombolytic therapy or primary
      angioplasty in patients with acute MI (ST-segment elevation).

PMID- 9539497
TI  - Use of abciximab in interventional cardiology.
AB  - The advent of platelet membrane glycoprotein (GP) IIb/IIIa inhibitors has changed
      the landscape of interventional cardiology. Given the commercial availability of
      abciximab and expected regulatory approvals for other receptor blockers, defining
      appropriate use of these agents in the interventional setting is mandated. One
      key issue is selection of patients who may benefit from GP IIb/IIIa receptor
      blockade. Focusing specifically on abciximab, data from three large-scale,
      randomized trials demonstrate that abciximab is appropriate for all patients
      undergoing percutaneous transluminal coronary angioplasty, regardless of risk
      stratum. Other important issues to consider when prescribing this therapy include
      benefits in conjunction with stents and new devices, dosing and timing of
      administration, and the role of prophylactic versus "bailout" administration.
      This article reflects a distillation of the views and consensus regarding the use
      of GP IIb/IIIa inhibitors in patients undergoing coronary intervention expressed
      by a group of international experts convened in Davos, Switzerland, February 16,
      1997. This report attempts to review clinical progress to date, formulate
      recommendations, and map out potentially fruitful lines of inquiry for future
      investigation.

PMID- 9539498
TI  - Safe use of platelet GP IIb/IIIa inhibitors.
AB  - The platelet membrane glycoprotein IIb/IIIa receptor inhibitor abciximab is used
      for the treatment of patients undergoing high-risk percutaneous coronary
      interventions and is used in approximately one third of coronary interventions in
      the United States and a growing number of procedures in Europe. Recent clinical
      trials have shown that this potent antiplatelet agent significantly reduces the
      incidence of death and nonfatal myocardial infarction and the need for
      revascularization. With expanding experience since the commercial release of
      abciximab in February 1995, several strategies to enhance the safety of abciximab
      have emerged. In particular, new data confirm that the risk of bleeding
      identified as a concern in the original EPIC trial-can be substantially reduced
      through the use of low-dose adjunctive heparin, early sheath removal, and
      fastidious postprocedure vascular access site care. Other recommendations for
      enhancing the safety of potent antiplatelet agents in a variety of clinical
      situations are provided. The following article reflects insights regarding the
      safety of glycoprotein IIb/IIIa inhibitors expressed by a group of international
      experts convened in Davos, Switzerland, February 16, 1997 This report attempts to
      review clinical progress to date, formulate recommendations, and map out
      potentially fruitful lines of inquiry for future investigation.

PMID- 9539499
TI  - Abciximab therapy in percutaneous intervention: economic issues in the United
      States.
AB  - Whether abciximab therapy should be the standard of care during percutaneous
      intervention in the United States depends on its efficacy, safety, and economics.
      In view of the EPIC, CAPTURE, and EPILOG data, few question the superior efficacy
      and relative safety of abciximab compared with conventional high-dose heparin
      therapy during percutaneous intervention. Economic considerations have been the
      major issue limiting its use. Review of the economic data demonstrates that the
      incremental direct medical care cost of abciximab therapy is $290 to $600 per
      patient treated in the EPIC and EPILOG populations. In the patients with acute
      myocardial infarction and unstable angina, abciximab appears to reduce direct
      medical costs (produce cost savings) at 6 months. Given abciximab's significant
      incremental effectiveness, its relatively small incremental cost yielded a highly
      cost-effective therapy in the EPIC and EPILOG patient populations. Additional
      economic issues relate to minimizing bleeding complications, indirect costs,
      reduced frequency of emergency procedures, and rationalizing provider/payor
      policies and incentives to produce the optimal individual patient and societal
      outcomes. The currently available data concerning the efficacy, safety, and cost
      provide a compelling argument for embracing abciximab therapy in the treatment of
      patient subsets where it will be a cost-saving or cost-neutral adjunct to
      percutaneous coronary intervention. In other subsets, the direct medical cost
      will likely not be fully recouped, but the incremental cost-effectiveness will
      compare favorably to other widely accepted therapies.

PMID- 9539500
TI  - Costs and effects in therapy for acute coronary syndromes: the case of abciximab
      in high-risk patients undergoing percutaneous transluminal coronary angioplasty
      in the EPIC study. Evaluation of 7E3 for the Prevention of Ischemic
      Complications.
AB  - Cost-effectiveness analyses are routinely performed to determine whether the
      additional cost of a novel therapy is balanced by additional effectiveness. The
      definitions of costs and effects involve a variety of assumptions, both in
      general economic terms and with regard to the specific medical setting under
      consideration. Similarly, differing criteria for acceptability of cost
      effectiveness estimates can be used to generate different conclusions regarding
      cost-effectiveness. The issues and problems inherent in economic evaluation are
      discussed by an analysis of findings with the platelet glycoprotein IIb/IIIa
      inhibitor abciximab in the EPIC (Evaluation of 7E3 for the Prevention of Ischemic
      Complications) study in high-risk patients undergoing percutaneous transluminal
      coronary angioplasty.

PMID- 9539501
TI  - Spontaneous vaginal delivery: a risk factor for Erb's palsy?
AB  - OBJECTIVE: Our purpose was to determine whether Erb's palsies occurring in the
      absence of shoulder dystocia differ from those occurring after shoulder dystocia.
      STUDY DESIGN: We compared the time course of resolution and incidence of
      persistent injury at 1 year of age in 17 cases of Erb's palsy without shoulder
      dystocia and 23 cases associated with shoulder dystocia. RESULTS: The rate of
      persistence at 1 year was significantly higher in those Erb's cases without
      identified shoulder dystocia, 7 of 17 (41.2%) versus 2 of 23 (8.7%), p = 0.04.
      These cases of Erb's palsies also took longer to resolve (6.4 +/- 0.9 vs 2.6 +/-
      0.7 months, p = 0.002), had a higher rate of associated clavicular fracture (12
      of 17 vs 5 of 23, p = 0.006), and were more likely to occur in the posterior arm
      (10 of 15 vs 4 of 21, p = 0.009). CONCLUSIONS: Erb's palsy occurring without
      shoulder dystocia may be a qualitatively different injury than that occurring
      with shoulder dystocia.

PMID- 9539502
TI  - The role of amniotic fluid L-selectin, GRO-alpha, and interleukin-8 in the
      pathogenesis of intraamniotic infection.
AB  - OBJECTIVE: Our purpose was to compare and correlate amniotic fluid GRO-alpha,
      interleukin-8, and L-selectin in patients with and without intraamniotic
      infection. STUDY DESIGN: Amniocentesis was performed on 45 pregnant women with
      preterm contractions, labor, or rupture of membranes. Fourteen patients had
      intraamniotic infection, and 31 did not. Intraamniotic infection was defined as
      the presence of a positive amniotic fluid culture. Amniotic fluid tests for Gram
      stain, glucose, neutrophil counts, creatinine, pH, and specific gravity were
      performed. Amniotic fluid levels of soluble L-selectin, interleukin-8, and GRO
      alpha were measured by an enzyme-linked immunoassay and normalized by amniotic
      fluid creatinine levels. The Mann-Whitney Utest and Spearman's rank correlation
      test were used for statistical analyses. RESULTS: Amniotic fluid median levels of
      soluble L-selectin, interleukin-8, and GRO-alpha were significantly higher in
      pregnant women with intraamniotic infection than in those without intraamniotic
      infection (soluble L-selectin: median 3334.6 ng/mg creatinine, range 408.4 to
      15,956.8 vs 717.2 ng/mg creatinine, range 129.4 to 4601.9, p = 0.009; GRO-alpha:
      median 841.6 ng/mg creatinine, range 28.1 to 8591.7 vs 56.8 ng/mg creatinine,
      range 0.0 to 440.2, p < 0.0001; interleukin-8: median 4932.7 ng/mg creatinine,
      range 0.0 to 55,058.7 vs 28.3 ng/mg creatinine, range 0.0 to 1161.6, p = 0.0004).
      Patients with intraamniotic infection had significantly higher amniotic fluid
      leukocyte counts and leukocyte esterase activities and significantly lower
      amniotic fluid glucose concentrations compared with those without intraamniotic
      infection. Amniotic fluid GRO-alpha, interleukin-8, and soluble L-selectin were
      positively correlated, and each was positively correlated with amniotic fluid
      leukocytes and negatively correlated with amniotic fluid levels of glucose.
      CONCLUSIONS: Our data indicate amniotic fluid GRO-alpha and interleukin-8 may be
      two potent leukocyte chemoattractants and activators, and L-selectin is rapidly
      shed from leukocytes in the amniotic fluid in patients with intraamniotic
      infection.

PMID- 9539503
TI  - Umbilical cord plasma erythropoietin levels in pregnancies complicated by
      maternal smoking.
AB  - OBJECTIVE: Our goal was to determine whether maternal smoking was associated with
      elevated umbilical cord erythropoietin, a marker for chronic hypoxia. STUDY
      DESIGN: Plasma erythropoietin levels were measured in umbilical cord plasma of
      222 newborns. There were 48 mothers who smoked and 174 nonsmokers. RESULTS: When
      all pregnancies were included, mean cord plasma erythropoietin levels were
      significantly higher in the smokers (78.0 +/- 15.3 mIU/ml) compared with the
      nonsmoking group (35.2 +/- 4.0 mIU/ml; p < 0.005). Regression analysis showed a
      significant positive correlation between the number of cigarettes smoked per day
      and cord plasma erythropoietin levels (r = 0.26, p < 0.0001). Smoking was
      associated with a significantly elevated risk (relative risk = 2.6, 95%
      confidence interval 1.7 to 10.9, p < 0.005) of fetal growth restriction. When
      pregnancies with fetal growth restriction were excluded from the analysis, the
      difference between the two groups remained significant (smokers 81.3 +/- 18.6, n
      = 38; nonsmokers 24.3 +/- 1.4, n = 164; p < 0.03). CONCLUSIONS: These results
      illustrate that smoking during pregnancy is associated with fetal growth
      restriction and significantly elevated umbilical cord erythropoietin levels.

PMID- 9539504
TI  - The effect of uterine contractions on intrapartum fetal heart rate analyzed by a
      computerized system.
AB  - OBJECTIVE: Our goal was to assess the effect of uterine activity on fetal heart
      rate indexes during the active phase of labor with a computerized fetal heart
      rate monitoring system. STUDY DESIGN: Twenty-six healthy women were studied in
      active labor without analgesia. Fetal heart rate was analyzed by a computerized
      system (Sonicaid, System 8000), providing a numeric analysis of the fetal heart
      rate indexes. Montevideo and Alexandria units were used for quantitative
      assessment of contractions. RESULTS: A significant correlation was found between
      Montevideo units and short-term variation (r = -0.62, p < 0.001), episodes of
      high (r = -0.48, p < 0.01) and low (r = 0.58, p < 0.01) fetal heart rate
      variation, and frequency of large accelerations (r = -0.49, p < 0.01). A
      significant correlation was also found between Alexandria units and short-term
      variation (r = -0.645, p < 0.001), episodes of high fetal heart rate variation (r
      = -0.58, p < 0.01), and frequency of large accelerations (r = -0.49, p < 0.01).
      CONCLUSIONS: In active labor fetal heart rate variability is significantly
      affected by the intensity and duration of contractions.

PMID- 9539505
TI  - Subtle ultrasonographic anomalies: do they improve the Down syndrome detection
      rate?
AB  - OBJECTIVE: Our purpose was to determine whether the identification of subtle
      anomalies further improves Down syndrome detection over standard ultrasonographic
      biometry and the detection of gross morphologic defects. STUDY DESIGN: The
      screening efficiency of clinodactyly, dilated renal pelvis (> or =4 mm),
      echogenic bowel, mild ventriculomegaly (> or =10 to 15 mm), and two-vessel cord
      was determined prospectively in midtrimester fetuses at amniocentesis. The
      screening efficiency of increased nuchal thickness and shortened long-bone length
      (standard biometry) and gross morphologic defects was determined for comparison.
      Multiple backward stepwise regression analysis was used to determine which subtle
      anomalies significantly correlated with Down syndrome detection rate and whether
      they increased Down syndrome detection over that with standard biometry and
      morphologic defects. RESULTS: Although all subtle anomalies except two-vessel
      cord correlated with the presence of Down syndrome on univariate analysis, only
      echogenic bowel (Wald chi2 = 15.0211, p = 0.0001) and clinodactyly (Wald chi2 =
      9.4273, p = 0.002) persisted in regression analysis of the subtle anomaly group.
      When either of the above-described anomalies was present, the detection rate for
      Down syndrome was 28.6%, p < 0.00001. For the combination of standard biometry
      (either increased nuchal thickness or short humerus) or gross anatomic defect,
      Down syndrome detection rate was 53.3% (p < 0.00000001). This increased to 63.2%
      (p < 0.00000001) when subtle anatomic defects (either echogenic bowel or
      clinodactyly) were included in the definition of an abnormal sonogram.
      CONCLUSION: Subtle anomalies, of which echogenic bowel and clinodactyly are the
      most significant, further increase Down syndrome screening efficiency over
      standard biometry or the finding of gross anatomic defect. Our data appear to
      support the addition of subtle anomaly findings to ultrasonographic screening for
      Down syndrome.

PMID- 9539506
TI  - Prospective evaluation of prenatal maternal serum screening for trisomy 18.
AB  - OBJECTIVE: Our goal was to evaluate the performance of prenatal serum screening
      for trisomy 18. STUDY DESIGN: All 40,762 samples for maternal serum testing
      (August 1991 to June 1994) with a trisomy 18-positive screen (n = 175, alpha
      fetoprotein < or =0.75 multiples of the median, unconjugated estriol < or =0.60
      multiples of the median, human chorionic gonadotropin < or =0.55 multiples of the
      median) were analyzed. Results of all amniocenteses, ultrasonographic studies,
      and birth or death certificate information were obtained from the Iowa Expanded
      Serum Screening Program, the Iowa Department of Public Health, and the Iowa Birth
      Defects Registry. RESULTS: We obtained the expected screen-positive rate for
      trisomy 18 (0.43%, 175/40,762). Fourteen samples from outside the state were
      excluded, which left 161 cases with outcome data obtained through amniocentesis
      (n = 121), birth certificates (n = 34), telephone contact (n = 2), or a sonogram
      indicating a nonviable gestation (n = 4). Of 121 screen-positive women undergoing
      amniocentesis, 119 had a normal karyotype and 2 had an abnormal karyotype: 69,XXY
      and 47,XY,+18. Of 36 who declined amniocentesis, none had findings consistent
      with aneuploidy on clinical neonatal examination. Of the 103 patients who had a
      detailed ultrasonographic study at the University of Iowa, 27 had a subtle fetal
      abnormality or growth alteration. Both cases with aneuploidy were in this group.
      An additional 7 cases of trisomy 18 without the typical trisomy 18 maternal serum
      screening pattern were diagnosed during this period either at amniocentesis
      performed because of increased Down syndrome risk indicated by serum screening (n
      = 1), by elevated alpha-fetoprotein level (n = 1), or by advanced maternal age (n
      = 2) with serum for screening drawn coincidentally, or they were diagnosed
      postnatally (n = 3). Three of the 7 cases had early second-trimester
      ultrasonographic examinations, and all showed abnormalities. CONCLUSIONS: The
      detection rate of trisomy 18 among patients offered amniocentesis was
      significantly lower (p < 0.05) than the expected rate (10/161 on the basis of
      published data). Combining serum screening with detailed ultrasonographic
      evaluations may improve predictive value by more precisely targeting
      amniocentesis toward those at highest risk.

PMID- 9539507
TI  - Doppler velocimetry of growth-restricted fetuses in an ovine model of placental
      insufficiency.
AB  - OBJECTIVE: With an ovine model in which growth restriction was induced by
      exposure to heat stress, our aims were as follows: (1) to describe the normal
      gestational age-related changes in Doppler velocimetry in the ovine fetal aorta
      and umbilical artery and (2) to compare Doppler velocimetry between heat-stressed
      and non-heat-stressed fetuses. STUDY DESIGN: Five ewes were exposed to heat
      stress for 55 days beginning at 35 days' gestation. Five ewes were not exposed
      and served as controls. Aortic and umbilical artery pulsed Doppler velocimetry
      was obtained, including the systolic/diastolic ratio, pulsatility index, and
      resistance index. Data were obtained between 50 and 120 days' gestation. Linear
      regression analysis was used to analyze gestational age-related changes in
      velocimetry. Comparison of mean index values between heat-stressed and non-heat
      stressed fetuses were made with analysis of variance. RESULTS: Heat-stressed
      fetuses demonstrated significantly higher systolic/diastolic ratios and
      pulsatility index values for both umbilical artery (p < 0.025; p < 0.033) and
      aorta (p < 0.017; p < 0.022) compared with controls. The umbilical artery and
      aortic resistance index values were not different between groups (p < 0.079; p <
      0.28). The slopes for each of the Doppler index values were negative in both
      normal and heat-stressed fetuses. Umbilical artery and aortic end-diastolic flows
      remained absent through the first 70 days of gestation in both groups.
      CONCLUSION: Doppler velocimetry index values decrease with increasing gestational
      age, reflecting decreased placental bed vascular resistance. The higher Doppler
      index values seen in the heat-stressed group are consistent with increased
      placental vascular resistance. The normal absence of diastolic flow until 70
      days' gestation is similar to the pattern described in humans.

PMID- 9539509
TI  - Prenatal prediction of neonatal outcome in the extremely low-birth-weight infant.
AB  - OBJECTIVE: Our goal was to identify prenatally available parameters that
      correlate with neonatal outcome and could be used for predicting such outcome in
      the extremely low-birth-weight pregnancy. STUDY DESIGN: From 1990 through 1995,
      obstetric and neonatal data of live-born nonanomalous singleton infants with
      birth weights between 400 and 1000 gm were reviewed. Only cases in which
      ultrasonographic biometry, including biparietal diameter, abdominal
      circumference, and femur length, was performed < or =3 days before delivery were
      included. Overall survival (defined as alive at discharge) and survival without
      specific severe neonatal morbidities (namely, retinopathy of prematurity [stage 3
      or 4], intraventricular hemorrhage [grade 3 or 4], periventricular leukomalacia,
      chronic lung disease, and deafness) were ascertained. The best combination of
      prenatal parameters for the prediction of overall survival and survival without
      severe morbidity was determined by backward stepwise logistic regression
      analyses. RESULTS: The most significant prenatal predictors of overall survival
      were the obstetric estimate of gestational age and the abdominal circumference
      (chi2 = 11.8036, p = 0.0006 and chi2 = 8.1862, p < 0.005, respectively). Survival
      without severe morbidity was also predicted by the same combination of parameters
      (chi2 = 21.9079, p = 0.0001 and chi2 = 6.538, p = 0.01, respectively). The
      estimated fetal weight was not a significant independent predictor of either
      category of outcome (chi2 = 0.1249, p = 0.72 and chi2 = 0.0361, p = 0.85,
      respectively). On the basis of the regression formulas, curves displaying the
      probabilities of overall survival and survival without severe morbidity with any
      combination of gestational age and abdominal circumference were developed.
      CONCLUSION: The combination of gestational age and the abdominal circumference
      measurements appears to be superior to any combination that included estimated
      fetal weight data for predicting neonatal outcome in the neonates weighing < or
      =1000 gm. We developed a mechanism for predicting neonatal outcome in this weight
      category on the basis of prenatally available parameters. This information could
      prove useful for both parental counseling and obstetric decision making.

PMID- 9539508
TI  - Expression of gelatinase B by trophoblast cells: down-regulation by progesterone.
AB  - OBJECTIVE: It is now accepted that gelatinase B (92 kd type IV collagenase) is
      involved in blastocyst implantation and trophoblast invasion. However, little is
      known about the regulation of this enzyme at the fetomaternal interface.
      Progesterone has been demonstrated to inhibit gelatinase B secretion from
      endometrial cells, myometrium, and cervical fibroblasts. Interestingly, the
      promotor of gelatinase B contains a progesterone-responsive element that may
      explain transcriptional activation of this metalloproteinase by progesterone. It
      may be hypothesized that progesterone secreted from trophoblast cells,
      representing the fetal part of the fetomaternal interface, may have a role in the
      regulation of gelatinase secretion and blastocyst implantation. STUDY DESIGN: To
      this end, use was made of first-trimester trophoblast cells obtained from first
      trimester pregnancy terminations. The trophoblast cells were separated by trypsin
      degradation and fractionation on Percoll gradients. Metalloproteinase activity
      was measured by zymography, and the expression of the gelatinase B messenger
      ribonucleic acid was determined by the solution hybridization/ribonuclease
      protection assay. RESULTS: Primary cell cultures of trophoblasts from first
      trimesters of pregnancy constitutively elaborated two species of type IV
      collagenases (gelatinase A and B) as assessed on a gelatin matrix. Treatment with
      progesterone decreased the accumulation of a gelatinase B species in a dose
      dependent fashion. Administration of a progesterone receptor antagonist
      onapristone (ZK-98.299) neutralized the progesterone inhibitory effect on the
      gelatinase B in a dose-dependent fashion, thus supporting the presumption that
      the progesterone effect is receptor mediated. Progesterone significantly
      attenuated the expression of gelatinase B by trophoblast cells, an effect that
      was neutralized by ZK-98.299. CONCLUSION: These observations provide strong
      indirect support for the participation of progesterone in the regulation of
      gelatinase B in trophoblast cells. It may be an important regulator of gelatinase
      production at the fetomaternal interface.

PMID- 9539510
TI  - Lipopolysaccharide enhances the transcription of prostaglandin H synthase-2 gene
      in primary human trophoblasts.
AB  - OBJECTIVE: Our purpose was to test the hypothesis that lipopolysaccharide
      potentiates the transcription of human placental prostaglandin H synthase-2 gene,
      a rate-limiting enzyme in prostaglandin synthesis. STUDY DESIGN: We transfected
      normal term cytotrophoblasts with a reporter vector containing either
      prostaglandin H synthase-1 or prostaglandin H synthase-2 promoters, cloned
      upstream of a luciferase. We correlated lipopolysaccharide effect on luciferase
      activity with enzyme expression and prostaglandin E2 production. RESULTS:
      Lipopolysaccharide (10 microg/ml) enhanced prostaglandin H synthase-2 but not
      prostaglandin H synthase-1 promoter activity. This effect was abolished by
      dexamethasone (10(-6) mol/L). Platelet-derived growth factor, a known stimulant
      of prostaglandin H synthase-2 in nonplacental tissue, had no effect on the
      activity of prostaglandin H synthase-2 promoter. Lipopolysaccharide induced the
      expression of prostaglandin H synthase-2 messenger ribonucleic acid fivefold to
      sixfold and caused a 3.5-fold increase in prostaglandin E2 production.
      CONCLUSION: Lipopolysaccharide enhances the transcription of prostaglandin H
      synthase-2 gene in human trophoblasts. Enhanced expression of prostaglandin H
      synthase-2 results in a higher production of prostaglandins, which may alter
      villous blood flow.

PMID- 9539511
TI  - Brain lipid peroxidation and antioxidant levels in fetal lambs 72 hours after
      asphyxia by partial umbilical cord occlusion.
AB  - OBJECTIVES: The purpose of this study was to explain the role of oxidative stress
      in the pathogenesis of brain damage caused by intrauterine fetal asphyxia. STUDY
      DESIGN: Six chronically instrumented near-term fetal lambs were subjected to
      asphyxia by partial umbilical cord occlusion for approximately 60 minutes until
      fetal arterial pH diminished to less than 6.9 and base excess to less than -20
      mEq. Another six fetuses surgically prepared but not occluded were used as
      control. Fetuses were killed after 72 hours and eight different brain regions
      (frontal and parietal gray matter, frontal and parietal white matter, basal
      ganglia, thalamus, hippocampus, and cerebellum) were dissected and assayed for
      thiobarbituric acid reactive substances, glutathione, and superoxide dismutase.
      RESULTS: Thiobarbituric acid reactive substance levels in asphyxiated animals
      were elevated in frontal and parietal white matter, basal ganglia, and thalamus
      compared with those in controls. The concentrations of superoxide dismutase in
      the asphyxiated group were also higher in frontal and parietal white matter,
      basal ganglia, and cerebellum compared with those in the control group. Between
      the two groups, however, glutathione concentrations did not differ significantly.
      CONCLUSION: These results suggest that oxidative stress may be a major
      contributing factor to the development of brain damage in intrauterine fetal
      asphyxia.

PMID- 9539512
TI  - Neonatal cranial ultrasonographic findings in preterm twins complicated by severe
      fetofetal transfusion syndrome.
AB  - OBJECTIVE: To investigate cranial ultrasonographic findings in survivors of
      monochorionic pregnancies complicated by fetofetal transfusion syndrome. STUDY
      DESIGN: Case details of all monochorionic twin pregnancies complicated by
      fetofetal transfusion syndrome were obtained from the Centre for Fetal Care
      database for a 3-year period. Fetofetal transfusion syndrome was diagnosed
      according to ultrasonographic criteria. Eligible for entry were twin pregnancies
      resulting in live-born preterm infants and complicated by fetofetal transfusion
      syndrome severe enough to require amnioreduction. Cranial ultrasonographic scans
      performed within 48 hours of birth were reviewed for evidence of abnormality.
      RESULTS: Seventeen pregnancies were eligible for inclusion in the study. Median
      gestational age was 25 weeks (between 17 and 29 weeks) at diagnosis and 30 weeks
      (between 25 and 35 weeks) at delivery. Three infants died before ultrasonography
      could be performed. The remaining 31 twin infants received an early cranial
      ultrasonographic scan. One of the 31 had a major cerebral infarct; 10 others had
      evidence of other, more minor, antenatally acquired lesions. CONCLUSIONS: Both
      donor and recipient survivors from pregnancies complicated by fetofetal
      transfusion syndrome are at significant risk for antenatally acquired cerebral
      lesions. Long-term neurologic follow-up studies are indicated to determine the
      clinical significance of these lesions.

PMID- 9539513
TI  - Human amniotic fluid mathematical model: determination and effect of
      intramembranous sodium flux.
AB  - OBJECTIVE: A recently described mathematical model of human amniotic fluid
      dynamics used known and estimated rates of fetal fluid production (lung liquid
      and urine) and composition (osmolality) to enable calculation of previously
      unmeasured routes of amniotic fluid resorption, including fetal swallowing and
      intramembranous (across the amnion) water flow. This "osmolar" model assumed that
      only free water resorption occurred across the intramembranous route. We
      hypothesized that intramembranous flow also may include solutes and electrolytes
      because significant concentration gradients exist between amniotic fluid and
      fetal plasma. We used mass balance analysis to determine the direction and
      magnitude of intramembranous sodium flux and to assess the ability of a newly
      described "sodium" model to predict changes in amniotic fluid volume in response
      to changes in intramembranous electrolyte flow. Mathematical modeling was used to
      predict changes in amniotic fluid volume in response to changes in
      intramembranous electrolyte flow. STUDY DESIGN: Model predictions were calculated
      using published values for human amniotic fluid and fetal urine composition and
      volume. Ovine studies were used to derive lung fluid volumes and composition.
      Fetal swallowing and intramembranous flow were independently determined using net
      amniotic fluid osmolar (osmolality model) and sodium (sodium model) balance.
      Differences between osmolality and sodium model predictions were normalized to
      calculate the net intramembranous sodium flux, assuming a net balance of
      intramembranous osmotic solute flow. RESULTS: Both sodium and osmolality models
      predicted swallowed volume to be greater than intramembranous flow until 28 to 32
      weeks' gestation, after which the relationship reversed. However, the sodium
      model predicted greater intramembranous flow and lower swallowing rates compared
      with the osmolality model at all gestational ages. Osmolar mass balance required
      daily intramembranous sodium flux into the amniotic fluid, which increased with
      gestational age. Furthermore, assuming stable swallowing and intramembranous
      water flow, the model predicts that 5% increases or decreases in amniotic fluid
      solute concentrations caused by intramembranous flux result in polyhydramnios or
      oligohydramnios, respectively. CONCLUSION: Sodium and osmolality models
      demonstrate similarities in determinations of amniotic fluid dynamics. However,
      mass balance equations demonstrate a net intramembranous flow of sodium into the
      amniotic fluid under normal conditions. Mathematical modeling suggests that small
      alterations in daily intramembranous sodium flux may evoke large changes in
      amniotic fluid volume.

PMID- 9539514
TI  - Higher endothelin concentrations in the fetoplacental unit of pregnant women of
      African ancestry.
AB  - Immunoreactive endothelin was assayed in maternal and fetal biologic fluids of
      women of African and European ancestry with normal singleton pregnancies
      undergoing cesarean section at term for obstetric reasons. Endothelin
      concentration was found to be higher in the umbilical vein and artery blood of
      women of African origin. Higher production of endothelins in the fetoplacental
      unit may place these women at a greater risk of preeclampsia.

PMID- 9539515
TI  - Cigarette smoking as a risk factor for ectopic pregnancy.
AB  - OBJECTIVE: Our purpose was to assess the risk of ectopic pregnancy among women
      who smoke cigarettes. STUDY DESIGN: We used data from a case-control study of
      ectopic pregnancy conducted from October 1988 to August 1990 at an inner-city
      hospital in Georgia. Cases were 196 non-Hispanic black women with a surgically
      confirmed ectopic pregnancy. Controls were non-Hispanic black women who had
      delivered either a live or a stillborn infant weighing at least 500 gm (n = 882)
      or who were pregnant and seeking an induced abortion (n = 237). RESULTS: After we
      adjusted for parity, douching history, history of infertility, and age, the odds
      ratio for ectopic pregnancy was 1.9 (95% confidence interval 1.4 to 2.7) for
      women who smoked during the periconception period compared with women who did not
      smoke at that time. After stratification by the amount of daily smoking during
      the periconception period, the odds ratio rose from 1.6 (95% confidence interval
      0.9 to 2.9) for women who smoked 1 to 5 cigarettes to 1.7 (95% confidence
      interval 1.1 to 2.8) for women who smoked 6 to 10 cigarettes to 2.3 (95%
      confidence interval 1.3 to 4.0) for women who smoked 11 to 20 cigarettes, and to
      3.5 (95% confidence interval 1.4 to 8.6) for women who smoked >20 cigarettes per
      day. CONCLUSION: In this inner-city population, cigarette smoking was an
      independent, dose-related risk factor for ectopic pregnancy among black women.
      The public health and medical care communities should inform the public of this
      additional risk associated with cigarette smoking and intensify intervention
      strategies to reduce cigarette smoking among women of reproductive age.

PMID- 9539516
TI  - Laparoscopy versus laparotomy: an evaluation of adhesion formation after pelvic
      and paraaortic lymphadenectomy in a porcine model.
AB  - OBJECTIVE: Our purpose was to determine whether there is a difference in adhesion
      formation after pelvic and paraaortic lymphadenectomy with transperitoneal
      laparoscopy compared with both extraperitoneal laparotomy and transperitoneal
      laparotomy in a porcine model. STUDY DESIGN: Ninety female hogs underwent pelvic
      and paraaortic lymphadenectomy: 40 with transperitoneal laparoscopy, 40 with
      extraperitoneal laparotomy, and 10 with transperitoneal laparotomy. Three weeks
      after the initial surgery, a laparotomy was performed to assess adhesion
      formation. RESULTS: The transperitoneal laparotomy group had significantly higher
      adhesion formation, with a 100% (10 of 10) adhesion rate. In the transperitoneal
      laparoscopy group, 12 of 40 hogs (30%) had adhesions develop versus 8 of 38 (21%)
      in the extraperitoneal laparotomy group (p = not significant). Also no
      differences were found in the transperitoneal laparoscopy and extraperitoneal
      laparotomy groups when comparing adhesion thickness or the total surface area of
      adhesions. More anterior abdominal wall adhesions were noted in the
      extraperitoneal laparotomy group (5 of 38) than in the transperitoneal
      laparoscopy group (0 of 40, p = 0.02). CONCLUSIONS: Pelvic and paraaortic
      lymphadenectomy performed with transperitoneal laparoscopy does not increase
      adhesion formation when compared with extraperitoneal laparotomy in a porcine
      model. The transperitoneal laparoscopy (and extraperitoneal laparotomy) approach
      also induces significantly fewer adhesions than transperitoneal laparotomy.

PMID- 9539517
TI  - Characteristics of luteinizing hormone secretion in younger versus older
      premenopausal women.
AB  - OBJECTIVES: The objectives of this study were to document specific attributes of
      pulsatile luteinizing hormone secretion in middle-aged women before discernible
      alterations in their menstrual cycles and to compare the results to corresponding
      data obtained in younger women. STUDY DESIGN: After documenting normal cycle
      length, biphasic basal body temperatures, and normal midluteal progesterone in
      younger and middle-aged women during an initial cycle, daily blood samples and
      samples withdrawn at 10-minute intervals for 8 hours during the midfollicular
      phase were obtained during a subsequent cycle. RESULTS: Assessment of luteinizing
      hormone pulses with the pulse detection algorithm Cluster demonstrated a
      prolonged interpulse interval and increased pulse width in the older women.
      Assessment of luteinizing hormone secretory bursts and half-life with the
      deconvolution analysis procedure demonstrated a prolonged interburst interval and
      half-life in the older women. Appraisal of approximate entropy revealed greater
      orderliness of luteinizing hormone release in the older women. CONCLUSIONS:
      Middle-aged women exhibit alterations in hypothalamic-pituitary function that may
      account in part for age-related changes in reproductive potential.

PMID- 9539518
TI  - Immunoglobulin A response against Gardnerella vaginalis hemolysin and sialidase
      activity in bacterial vaginosis.
AB  - OBJECTIVE: The aim of this study was to investigate the correlation between the
      immunoglobulin A immune response to Gardnerella vaginalis hemolysin and sialidase
      activity in vaginal fluids from patients with bacterial vaginosis. STUDY DESIGN:
      Nonpregnant women who were examined at a gynecologic clinic, in an age range of
      18 to 62 years, were enrolled. The study population comprised 131 healthy
      volunteers, 32 women with bacterial vaginosis that was positive for
      immunoglobulin A to Gardnerella vaginalis hemolysin, 40 women with bacterial
      vaginosis that was negative for immunoglobulin A to Gardnerella vaginalis
      hemolysin, and 19 women with Candida vaginitis. Bacterial vaginosis was diagnosed
      by clinical criteria and Gram stain. RESULTS: Sialidase activity was present in
      75% (54/72) of patients with bacterial vaginosis. Women having bacterial
      vaginosis and lacking a specific immunoglobulin A response had a significantly
      higher level of sialidase activity than patients who had an immune response
      against Gardnerella vaginalis hemolysin. Sialidase activity was detected in 87%
      (35/40) of the former subgroup of patients with bacterial vaginosis and in 59%
      (19/32) of women of the latter subgroup. No sialidase activity was measured in
      patients with candidiasis. Specificity of the assay for healthy controls was 95%
      (124/131 women without sialidase activity). CONCLUSIONS: Sialidases produced by
      Prevotella bivia and other microorganisms present in the microflora of patients
      with bacterial vaginosis are very likely a virulence factor not only by
      destroying the mucins and enhancing adherence of bacteria but also by impairing a
      specific immunoglobulin A immune response against other virulence factors such as
      cytotoxin from Gardnerella vaginalis.

PMID- 9539519
TI  - The course of labor with and without epidural analgesia.
AB  - OBJECTIVE: Our purpose was to measure effects of epidural analgesia on labor
      compared with boluses of meperidine in a cohort of women with similar clinical
      circumstances. STUDY DESIGN: One hundred ninety-nine nulliparous women who were
      delivered spontaneously at term and who received oxytocin for labor augmentation
      before the initiation of analgesia were identified for analysis. All these women
      were managed in a low-risk labor unit according to a standardized protocol. This
      management protocol encouraged early amniotomy and the use of oxytocin when
      ineffective labor was diagnosed. RESULTS: The demographic characteristics of the
      two study groups were similar with respect to age, height, weight, and maternal
      age. The two groups had the same cervical dilatation on admission (3.3 cm) and at
      the time of analgesia administration (4.1 vs 4.2 cm), indicating similar progress
      of labor before oxytocin administration. The length of the active phase of labor
      was longer in the epidural group (7.9 vs 6.3 hours, p = 0.005), as was the second
      stage (60 vs 48 minutes, p = 0.03). The mean and maximal rates of oxytocin
      infusion were similar between the two study groups; however, the amount of
      oxytocin required for each centimeter of cervical change was more in the epidural
      group (22 vs 16 mU per cm of cervical change, p = 0.009). Neonatal outcomes were
      unaffected by the type of labor analgesia. CONCLUSION: Epidural analgesia
      decreases uterine performance during oxytocin-stimulated labor, resulting in an
      increase in the length of the first and second stages of labor.

PMID- 9539520
TI  - Automated, ambulatory, or conventional blood pressure measurement in pregnancy:
      which is the better predictor of severe hypertension?
AB  - OBJECTIVES: Our purpose was to investigate the benefit, if any, of automated
      blood pressure monitoring over obstetric day unit conventional blood pressure
      measurement in the assessment of hypertensive pregnancies. STUDY DESIGN: A
      prospective, observational study was carried out in two large teaching hospitals.
      Three hundred and forty-eight women with a confirmed clinic blood pressure of at
      least 140/90 mm Hg were recruited. Conventional blood pressure measurements (< or
      =5) were obtained on the day unit and simultaneously an ambulatory blood pressure
      monitor was applied for 24 hours. The predictive ability of day unit assessment
      (blood pressure > 140/90 mm Hg) and automated blood pressure monitoring (blood
      pressure > 130/85 mm Hg) was compared. Principal outcome measures included the
      occurrence of severe hypertension (> 160/110 mm Hg) and proteinuria (> 500 mg or
      2+) within (a) 2 weeks and (b) the remainder of the pregnancy. Thompson's method
      was used to compare sensitivity and specificity of the day unit blood pressure
      and automated blood pressure monitoring. RESULTS: Three hundred and forty-eight
      women were recruited to the study. The comparison between automated blood
      pressure monitoring and conventional blood pressure measurement for both
      sensitivity and specificity for systolic and diastolic blood pressure revealed
      increased sensitivity and decreased specificity with automated blood pressure
      monitoring for all principal outcomes except development of proteinuria for
      systolic blood pressure. Sensitivity for the outcomes was increased with
      automated blood pressure monitoring by between 14% and 27% for systolic blood
      pressure and between 7% and 39% for diastolic blood pressure, with the greatest
      improvement seen for the development of severe hypertension within 2 weeks of
      assessment. CONCLUSIONS: In the assessment of hypertensive pregnancies, automated
      blood pressure measurement was a significantly better predictor (compared with
      conventional day unit assessment) for the development of severe hypertension
      within 2 weeks of assessment for both systolic and diastolic blood pressure.

PMID- 9539521
TI  - Cardiac hypertrophy in chronically anemic fetal sheep: Increased vascularization
      is associated with increased myocardial expression of vascular endothelial growth
      factor and hypoxia-inducible factor 1.
AB  - OBJECTIVE: Our purpose was to determine whether the increase in fetal cardiac
      mass and cardiac output in chronic anemia is accompanied by changes in capillary
      density or size or changes in levels of vascular endothelial growth factor and
      hypoxia-inducible factor 1, a basic helix-loop-helix transcription factor that
      has previously been shown to activate vascular endothelial growth factor gene
      transcription when cultured cells are subjected to hypoxia. STUDY DESIGN: Anemia
      was induced in near-term ovine fetuses by daily isovolemic hemorrhage. In five
      fetuses the heart was arrested in diastole, isolated, and fixed at physiologic
      pressures with adenosine-paraformaldehyde, and morphometric measurements of
      capillaries were made. In six fetuses cardiac expression of vascular endothelial
      growth factor and hypoxia-inducible factor 1 protein was detected by Western
      analysis and vascular endothelial growth factor messenger ribonucleic acid by
      Northern blot analysis. Eleven age-matched fetuses served as controls. RESULTS:
      The anemic fetuses compared with controls had a lower hematocrit (14.8% +/- 0.7%
      vs 35.3% +/- 1.5%) and a greater heart-to-body weight ratio (10.5 +/- 1.1 vs 7.7
      +/- 0.5 gm/kg). The minimal capillary diameter was increased and the
      intercapillary distance was decreased in both right and left ventricles of anemic
      fetuses compared with controls. Vascular endothelial growth factor protein was
      increased 4.5-fold, vascular endothelial growth factor messenger ribonucleic acid
      3.2-fold, and hypoxia-inducible factor 1alpha protein 3.8-fold in ventricular
      tissue from anemic fetuses. CONCLUSIONS: In chronic fetal anemia cardiac
      hypertrophy is accompanied by anatomic changes in myocardial capillary
      morphometry along with induction of hypoxia-inducible factor 1 and vascular
      endothelial growth factor. These results provide evidence for a pathway by which
      anemia-hypoxia may stimulate myocardial vascularization.

PMID- 9539522
TI  - Secretory component of immunoglobulin A in maternal serum and the prediction of
      preterm delivery.
AB  - OBJECTIVE: Our purpose was to determine whether the secretory component of
      immunoglobulin A in maternal serum predicts delivery before 34 weeks' gestation.
      STUDY DESIGN: Primigravid women of an urban population in New Zealand were
      recruited at booking into a prospective longitudinal nested case control study (n
      = 1651; after exclusions and withdrawals, n = 1511). Serum was collected at 8 to
      12 weeks, 15 to 18 weeks, 21 to 24 weeks, 28 to 30 weeks, and 36 to 38 weeks of
      gestation and 6 weeks post partum. Concentrations of the secretory component of
      immunoglobulin A were determined by enzyme-linked immunosorbent assay in all
      women who were delivered preterm (n = 53) and in controls randomly selected from
      women delivered at > or =37 weeks' gestation (n = 178). RESULTS: Serum
      concentrations of the secretory component of immunoglobulin A were similar in
      women delivered at term or preterm throughout pregnancy (n = 21 delivered at <34
      weeks and n = 32 at 34 to 36.9 weeks, incidence 3.5%). Receiver-operator
      characteristic curves showed no discriminating ability of the secretory component
      of immunoglobulin A. Smokers had 50% higher concentrations than nonsmokers did (p
      < 0.0001 by analysis of variance). CONCLUSION: The secretory component of
      immunoglobulin A in maternal serum does not predict preterm delivery in a low
      risk population.

PMID- 9539523
TI  - Cervical fetal fibronectin correlates to prostaglandin E2-induced cervical
      ripening and can be identified in cervical tissue.
AB  - OBJECTIVE: Our purpose was to investigate whether prostaglandin E2-induced
      cervical ripening can be related to changes in fetal fibronectin levels and
      whether fetal fibronectin can be detected by immunohistochemistry in amniotic and
      cervical tissue. STUDY DESIGN: Fetal fibronectin levels in cervical mucus were
      quantitated in 28 nulliparous term pregnant women with unfavorable cervical
      states before and after intracervical application of prostaglandin E2 gel. The
      concentration of fetal fibronectin was determined with use of an enzyme
      immunoassay. Cervical biopsy specimens and amniotic tissue for
      immunohistochemical analysis were obtained from three term pregnant women and
      after parturition in three women. Cervical biopsy specimens from two nonpregnant
      women served as controls. Immunohistochemical analysis was performed with
      antibodies directed toward fetal fibronectin. RESULTS: The fetal fibronectin
      level in cervical mucus was low in all women before prostaglandin E2 application.
      In women with a successful prostaglandin E2-induced ripening (i.e., an increase
      of cervical score with > or =3 points), a tenfold increase in the fetal
      fibronectin level was registered. In women with an insufficient cervical ripening
      after prostaglandin E2 treatment no significant increase in the fetal fibronectin
      level was registered. The immunohistochemical analyses have identified fetal
      fibronectin in the epithelial cells of the cervix uteri. CONCLUSION: Successful
      prostaglandin E2-induced cervical ripening seems to be related to a significant
      increase in cervical fetal fibronectin levels. Fetal fibronectin can be detected
      immunohistochemically in the pregnant human cervix.

PMID- 9539524
TI  - Elevated second-trimester amniotic fluid interleukin-6 levels predict preterm
      delivery.
AB  - OBJECTIVE: Our purpose was to determine whether early second-trimester amniotic
      fluid interleukin-6 levels predict delivery before 34 weeks' gestation. STUDY
      DESIGN: We used stored second-trimester amniotic fluid samples obtained from
      women undergoing genetic amniocentesis from 1988 to 1996. Interleukin-6 levels
      were measured by enzyme-linked immunosorbent assay in samples from every case
      known to result in delivery from 20 to 34 weeks' gestation (n = 290), and 290
      matched controls delivering at > or =37 weeks. Fetal aneuploidies, anomalies, and
      all cases delivering within 30 days of the amniocentesis (which were thought to
      be possibly procedure related) were excluded. RESULTS: Interleukin-6 levels were
      higher in cases than controls (1.9 +/- 5.2 vs 1.0 +/- 2.4 ng/ml, p = 0.004).
      Cases were grouped according to whether the preterm delivery was indicated or
      spontaneous: The mean interleukin-6 levels were significantly higher than
      controls in the spontaneous group (1.6 +/- 3.2 vs 0.8 +/- 1.2 ng/ml, p = 0.01)
      but not in the indicated group (1.4 +/- 4.0 vs 0.8 +/- 1.2 ng/ml, p = 0.12). In
      all samples the interleukin-6 level was negatively correlated with the
      gestational age at delivery (R = -0.11633, p = 0.007). CONCLUSION: Elevated early
      second-trimester amniotic fluid interleukin-6 levels are associated with preterm
      delivery, confirming that in some women this indicator of very early intrauterine
      inflammation predicts birth before 34 weeks' gestation.

PMID- 9539525
TI  - Plasma concentrations of asymmetric dimethylarginine, a natural inhibitor of
      nitric oxide synthase, in normal pregnancy and preeclampsia.
AB  - OBJECTIVE: We investigated the change in the plasma concentration of asymmetric
      dimethylarginine, an endogenous inhibitor of nitric oxide synthase, in early-,
      mid-, and late-gestation normotensive pregnancies and in gestational age-matched
      preeclamptic pregnancies and compared the observed changes with changes in blood
      pressure. STUDY DESIGN: Blood pressure and peripheral plasma asymmetric
      dimethylarginine concentrations were measured in 20 nonpregnant and 145 pregnant
      women (33 first-trimester, 50 second-trimester, and 44 third-trimester
      normotensive pregnancies and 18 third-trimester pregnancies complicated by
      preeclampsia). In 23 normotensive pregnancies serial plasma asymmetric
      dimethylarginine concentrations were measured. Statistical analysis was by
      analysis of variance and linear regression. RESULTS: The blood pressures recorded
      throughout normal pregnancy were significantly lower than in nonpregnant subjects
      (p < 0.0001). The mean systolic, diastolic, and average blood pressures were
      significantly higher in the second-trimester groups than in the first-trimester
      groups, whereas in the third trimester average and diastolic blood pressures were
      significantly higher than in the second trimester. The mean (+/-SD) systolic and
      diastolic blood pressures in third-trimester preeclamptic patients was 157.7 +/-
      11.2 and 110.9 +/- 8.5 mm Hg. The mean plasma asymmetric dimethylarginine
      concentration in nonpregnant women was 0.82 +/- 0.31 micromol/L (significantly
      higher than in normotensive pregnancy, p < 0.0001). The plasma asymmetric
      dimethylarginine concentration was also significantly higher in second-trimester
      than in first-trimester normotensive groups (respectively, 0.52 +/- 0.20
      micromol/L and 0.40 +/- 0.15 micromol/L, p = 0.001) and was higher in third
      trimester normotensive pregnancy 0.56 +/- 0.23 micromol/L than it was in the
      second trimester. The asymmetric dimethylarginine concentration in third
      trimester preeclamptic patients was 1.17 +/- 0.42 micromol/L (p < 0.0001 vs
      normotensive third-trimester subjects). CONCLUSIONS: It is well recognized that
      blood pressure falls in early normal pregnancy and rises again toward term. These
      studies show that the early fall in blood pressure is accompanied by a
      significant fall in the plasma asymmetric dimethylarginine concentration. Later
      in pregnancy circulating concentrations increase and, when pregnancy is
      complicated by preeclampsia, concentrations are higher than in the nonpregnant
      state. Our data support a role for both asymmetric dimethylarginine and nitric
      oxide in the changes in blood pressure seen in both normal and preeclamptic
      pregnancy.

PMID- 9539526
TI  - Expression of cell adhesion molecules by endothelium in the human lower uterine
      segment during parturition at term.
AB  - OBJECTIVE: Our purpose was to determine whether the expression of certain
      adhesion molecules by endothelium in the human lower uterine segment at term
      varies with the degree of cervical dilatation. STUDY DESIGN: Biopsy specimens of
      the lower uterine segment of 34 women undergoing cesarean section at term at
      various stages of cervical dilatation were immunostained for endothelial
      leukocyte adhesion molecule-1, intercellular adhesion molecule-1, vascular cell
      adhesion molecule-1, and platelet-endothelial cell adhesion molecule. RESULTS:
      The expression of endothelial leukocyte adhesion molecule-1 was significantly
      greater at more than 6 cm dilatation than at less than 2 cm (p = 0.00031) as was
      that of vascular cell adhesion molecule-1 (p = 0.033). Expression of
      intercellular adhesion molecule-1 and platelet-endothelial cell adhesion molecule
      did not vary with the degree of cervical dilatation. CONCLUSION: Cervical
      dilatation is associated with up-regulation of certain endothelial cell adhesion
      molecules. The findings support the hypothesis that certain processes associated
      with cervical dilatation at term resemble those involved in the acute
      inflammatory reaction.

PMID- 9539527
TI  - The preterm prediction study: risk factors for indicated preterm births. Maternal
      Fetal Medicine Units Network of the National Institute of Child Health and Human
      Development.
AB  - OBJECTIVE: Preterm births occur for many different reasons. Most efforts to
      identify risk factors for preterm births either ignore cause and consider preterm
      births as a single entity or examine risk factors for spontaneous preterm births.
      We performed this study to examine risk factors for indicated preterm births,
      which constitute more than one quarter of all preterm births. STUDY DESIGN: The
      study included 2929 women evaluated at 24 weeks' gestation at 10 centers.
      Information was gathered about demographic factors, socioeconomic status, home
      and work environments, drug and alcohol use, and medical history. In addition
      vaginal samples were evaluated for fetal fibronectin and bacterial vaginosis and
      cervical length was measured by transvaginal ultrasonography. Associations with
      indicated preterm birth were evaluated by univariate tests and by multivariable
      analysis with logistic regression. RESULTS: Of the women studied at 24 weeks'
      gestation 15.3% were delivered of their infants at <37 weeks' gestation. Of these
      deliveries, 27.7% were indicated preterm births. Risk factors in the final
      multivariable model were, in order of decreasing odds ratios, mullerian duct
      abnormality (odds ratio 7.02), proteinuria at <24 weeks' gestation (odds ratio
      5.85), history of chronic hypertension (odds ratio 4.06), history of previous
      indicated preterm birth (odds ratio 2.79), history of lung disease (odds ratio
      2.52), previous spontaneous preterm birth (odds ratio 2.45), age >30 years (odds
      ratio 2.42), black ethnicity (odds ratio 1.56), and working during pregnancy
      (odds ratio 1.49). Alcohol use in pregnancy was actually associated with a lower
      risk of indicated preterm birth (odds ratio 0.35). CONCLUSION: The risk factors
      found in this analysis tend to be different from those associated with
      spontaneous preterm birth.

PMID- 9539528
TI  - Fetal oxygen saturation and fractional extraction at birth and the relationship
      to measures of acidosis.
AB  - OBJECTIVE: We sought to determine umbilical cord oxygen saturation and fractional
      oxygen extraction values as measured at birth for a large tertiary hospital
      population and their predictive value for measures of acidosis. STUDY DESIGN: The
      computerized perinatal database of St. Joseph's Health Centre, London, Ontario,
      was used to obtain the umbilical cord gases, pH, mode of delivery, gestational
      age at delivery, and nuchal cord status for all live-born infants >500 gm between
      January 1991 and December 1995 (n = 22,134). Oxygen saturation values were
      calculated from the umbilical cord PO2 and pH data with a previously derived
      empirical equation, the accuracy of which was rechecked with 100 consecutive cord
      blood samples where oxygen saturation values were both calculated and measured
      with a hemoximeter (r = 0.99, p = 0.001). Fractional oxygen extraction values
      were calculated from the umbilical cord oxygen saturation data. RESULTS: There
      were 18,250 "validated" paired umbilical vein and artery blood gas and pH results
      available for analysis after patient case exclusions for missing, unreliable, or
      "unphysiologic" data. For all validated patient cases, mean umbilical vein oxygen
      saturation was 63% +/- 16% (SD), mean umbilical artery oxygen saturation was 24%
      +/- 15%, and mean fractional oxygen extraction was 0.62 +/- 0.20, with all three
      of these parameters significantly affected by mode of delivery, gestational age
      at delivery, and nuchal cord status. Umbilical vein and artery oxygen saturation
      and fractional oxygen extraction values showed significant relationships with
      umbilical artery base excess, albeit weak (r = 0.18 to 0.22), and pH (r = 0.46),
      which were best described using cubic regression models. Receiver-operator
      characteristic curve statistics for the prediction of acidosis at birth were also
      significant for all three of these parameters but lower when predicting metabolic
      versus mixed acidosis. However, all showed a poor positive predictive value for
      significant acidosis at birth, whether metabolic or mixed and regardless of the
      cutoff values used. CONCLUSION: Umbilical cord oxygen saturation and fractional
      oxygen extraction values as measured at birth for a large tertiary hospital
      population indicate a decreased oxygen margin of safety for infants born
      postterm, by cesarean section after labor, and with a nuchal cord. However, these
      values have a limited relationship to measures of acidosis, which may have
      clinical implications for the usefulness of intrapartum pulse oximetry.

PMID- 9539529
TI  - Few microorganisms associated with bacterial vaginosis may constitute the
      pathologic core: a population-based microbiologic study among 3596 pregnant
      women.
AB  - OBJECTIVE: To evaluate the association between various microorganisms isolated
      from the genital tract in pregnant women with bacterial vaginosis. STUDY DESIGN:
      A cross-sectional population-based study among pregnant women addressed at their
      first antenatal visit before 24 full gestational weeks from the referring area of
      the Department of Obstetrics and Gynecology at Odense University Hospital,
      Denmark, from November 1992 to February 1994. The main outcome measures were
      prevalence of various microorganisms and statistical estimates of interactions
      (crude, adjusted, and relative odds ratios) between the microorganisms isolated
      from the lower genital tract in pregnant women with and without clinical
      diagnosis of bacterial vaginosis. RESULTS: Three thousand five hundred ninety-six
      (3596) pregnant women were asked to participate. Of the 3596 pregnant women 3174
      (88.4%) agreed to participate before 24 full gestational weeks. After controlling
      for the presence of other microorganisms, strong associations between Gardnerella
      vaginalis, anaerobic bacteria, Mycoplasma hominis, and present bacterial
      vaginosis were found. Similarly Lactobacillus spp. were found to be associated
      with the absence of bacterial vaginosis. The combination of G. vaginalis and
      anaerobic bacteria and/or M. hominis was found in 59.6% of the cases with
      bacterial vaginosis and in 3.9% of the cases without bacterial vaginosis (odds
      ratio 36.4, 95% confidence interval 27.8 to 47.8). The crude odds ratio was found
      to be as high as 74.8 (95% confidence interval 32.3 to 174.1) when the
      combination of G. vaginalis, M. hominis, anaerobic bacteria, and no Lactobacillus
      spp. was associated with bacterial vaginosis. CONCLUSION: There is a microbial
      foundation for bacterial vaginosis, and it is possibly due to an intermicrobial
      interaction in which the microorganisms G. vaginalis, anaerobic bacteria, and M.
      hominis are dominating, indicating that these constitute the pathologic core of
      bacterial vaginosis.

PMID- 9539530
TI  - Gap junction currents in cultured muscle cells from human myometrium.
AB  - OBJECTIVE: The electrophysiologic properties of gap junctions between human
      myometrial smooth muscle cells were studied. STUDY DESIGN: Double whole-cell
      patch clamp recordings were made on pairs of cells from primary cultures of
      myometrial cells from women undergoing cesarean section. Macroscopic gap junction
      currents were measured as the change in current in a cell held at a constant
      voltage while the other member of a pair was subjected to a test pulse of
      voltage. The blockade by halothane was examined. RESULTS: Mean junctional
      conductance between pairs of cells was 23 +/- 14 nanosiemens (n = 57).
      Instantaneous gap junction conductance was constant as a function of
      transjunctional voltage. For transjunctional voltages of < or = 50 mV, currents
      were constant during a 5-second test pulse. For larger voltages, however, the
      currents showed a time-dependent decay. The currents were blocked completely and
      reversibly with 3.5 mmol/L halothane. Single-channel conductances of 60
      picosiemens and 15 picosiemens were observed. CONCLUSION: This first study of gap
      junction currents in human myometrial cells confirms that connexin43 is the major
      functional constituent. Functional studies of myometrial gap junction channels
      may suggest new strategies for controlling uterine contractility.

PMID- 9539531
TI  - The one-year morphometric and neurodevelopmental outcome of the offspring of
      women who continued to exercise regularly throughout pregnancy.
AB  - OBJECTIVE: Our purpose was to test the hypothesis that continuing regular
      exercise throughout pregnancy alters morphometric and neurodevelopmental outcome
      at 1 year. STUDY DESIGN: The offspring of 52 women who exercised were compared
      with those of 52 control subjects who were similar in terms of multiple prenatal
      and postnatal variables known to influence outcome. All women were enrolled
      before pregnancy and had clinically normal antenatal and postnatal courses.
      Neurodevelopment was assessed by blinded examiners at 1 year of age, and
      morphometrics were obtained at birth and at 1 year of age. RESULTS: At birth, the
      offspring of the exercising women weighed less (3.38 +/- 0.06 kg vs 3.58 +/- 0.07
      kg) and had less body fat (9.5% +/- 0.8% vs 12.6% +/- 0.6%). However, at 1 year,
      all morphometric parameters were similar, and no clinically significant between
      group differences were observed in performance on either the Bayley psychomotor
      (108 +/- 1 vs 101 +/- 2) or mental (120 +/- 1 vs 118 +/- 1) scales. CONCLUSIONS:
      These data indicate that the offspring of exercising mothers have normal growth
      and development during the first year of life.

PMID- 9539532
TI  - The significance of prenatally identified isolated clubfoot: is amniocentesis
      indicated?
AB  - OBJECTIVE: Our purpose was to determine the significance of finding an isolated
      clubfoot on a prenatal sonogram. STUDY DESIGN: All fetuses found to have an
      isolated congenital clubfoot over a 9-year period were retrospectively
      identified. Fetuses with associated anomalies were excluded. Review of medical
      records for obstetric and neonatal outcome and pathologic and cytogenic results
      were tabulated. RESULTS: Eighty-seven fetuses were identified from our database
      as having isolated clubfoot on prenatal ultrasonography, with complete follow-up
      available for 68 fetuses. Sixty of the 68 fetuses were confirmed as having
      clubfoot after delivery (false-positive rate = 11.8%). The male/female ratio was
      2:1. Four fetuses (5.9%) had abnormal karyotypes: 47,XXY, 47,XXX, trisomy 18, and
      trisomy 21. Nine fetuses had hip or other limb abnormalities noted after birth.
      Other anomalies not detected until delivery included a unilateral undescended
      testis, ventriculoseptal defects (n = 2), hypospadias (n = 2), early renal
      dysplasia, mild posterior urethral valves, and a two-vessel cord. Five of the 68
      patients (including those with aneuploidy) had pregnancy terminations. Eleven
      patients were delivered preterm. CONCLUSION: Karyotypic evaluation is recommended
      when isolated clubfoot is identified on prenatal sonogram because other subtle
      associated malformations may not be detected ultrasonographically in the early
      second trimester.

PMID- 9539533
TI  - Pregnancy complications are frequent in long-chain 3-hydroxyacyl-coenzyme A
      dehydrogenase deficiency.
AB  - OBJECTIVE: Preeclampsia-related complications of pregnancy have been detected in
      carriers of long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency, a
      recently discovered disorder of mitochondrial fatty acid oxidation. Because no
      comprehensive study is available, we studied the frequency of pregnancy
      complications in mothers who had given birth to children with this disorder.
      STUDY DESIGN: Data of all pregnancies of 18 mothers to 28 diagnosed patients with
      long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency were reviewed
      retrospectively. From a total 79 pregnancies 16 early abortions were excluded; 63
      pregnancies were included, and the fetus was affected in 29. RESULTS: One child
      born prematurely died neonatally but none of the mothers died. Preeclampsia, the
      syndrome of hemolysis, elevated liver enzymes, and low platelets, and acute fatty
      liver of pregnancy occurred in 31% and intrahepatic cholestasis in 10% of
      pregnancies with a long chain 3-hydroxyacyl-coenzyme A-deficient fetus but in
      none of the pregnancies with a healthy fetus. A total of 40% of affected neonates
      were born prematurely and 47% had growth restriction, whereas none of the healthy
      neonates were premature and growth restriction occurred in only 17% (p < 0.01).
      Prematurity and growth restriction could not be explained solely by the
      preeclampsia-related conditions. CONCLUSIONS: In pregnancies with a long-chain 3
      hydroxyacyl-coenzyme A-deficient fetus the frequency of preeclampsia-related
      conditions is high. The results support the role of fatty acid accumulation in
      the pathogenesis of preeclampsia. Analysis for the prevalent mutation of this
      deficiency may be warranted in pregnancies with severe preeclampsia.

PMID- 9539534
TI  - Symphyseal separation and transient femoral neuropathy associated with the
      McRoberts' maneuver.
AB  - Many authors have recommended the McRoberts' maneuver as the initial technique in
      the management of shoulder dystocia. There have been, however, no reported
      adverse maternal outcomes associated with this technique. We report a case of
      symphyseal separation and transient femoral neuropathy associated with the
      McRoberts' maneuver. An overly exaggerated lithotomy position and thigh abduction
      stretches the articular surfaces of the symphysis pubis and places increased
      pressure on the femoral nerve by the overlying inguinal ligament.

PMID- 9539535
TI  - Natural pregnancy in hypothyroid woman complicated by spontaneous ovarian
      hyperstimulation syndrome.
AB  - A unique case of life-threatening spontaneous ovarian hyperstimulation syndrome,
      resulting from severe untreated hypothyroidism, was observed in a woman who
      conceived spontaneously and gave birth to a normal viable infant.

PMID- 9539536
TI  - Intracranial cavernous angioma initially presenting in pregnancy with new-onset
      seizures.
AB  - A case of an intracranial cavernous angioma, which presented with headaches and
      seizures in a pregnant patient, is described. Diagnosis was established with
      magnetic resonance imaging. A computer-assisted literature search uncovered no
      previously reported case of intracranial cavernous angioma initially presenting
      during pregnancy.

PMID- 9539537
TI  - Urethral prolapse after collagen injection.
AB  - A woman who was treated for intrinsic urethral sphincteric deficiency with
      periurethral injection of glutaraldehyde cross-linked collagen had prolapse of
      the urethral mucosa and recurrence of incontinence. She subsequently required
      surgical resection and a fascia lata sling. This is the first known occurrence of
      this postinjection complication.

PMID- 9539538
TI  - First-trimester diagnosis of placenta previa percreta by magnetic resonance
      imaging.
AB  - Placenta previa percreta with bladder involvement is a rare but devastating
      complication of pregnancy. Antepartum diagnosis of this serious condition allows
      the obstetrician to alter his or her management of abdominal delivery and
      minimize the magnitude of bleeding. We report a case in which magnetic resonance
      imaging was able to detect placenta percreta in the first trimester. If further
      research demonstrates usefulness of this diagnostic modality, magnetic resonance
      imaging may prove to be useful in caring for patients with this condition.

PMID- 9539540
TI  - Intravenous leiomyomatosis with cardiac involvement in a pregnant woman.
AB  - Intravenous leiomyomatosis is a rare benign neoplasm that commonly grows into the
      pelvic veins and the inferior vena cava and, rarely, the right side of the heart.
      We report the first case of intravenous leiomyomatosis with cardiac involvement
      in a pregnant woman. The treatment of choice is surgical resection in two steps.

PMID- 9539539
TI  - Percutaneous transluminal endovascular graft placement for massive hemorrhage
      caused by recurrent cervical carcinoma-associated erosion of the external iliac
      artery.
AB  - Massive hemorrhage and shock resulting from inoperable recurrent cervical
      carcinoma-associated erosion of the left external iliac artery was treated with
      percutaneous transluminal placement of an endovascular graft with immediate
      hemostasis and maintenance of lower-extremity perfusion.

PMID- 9539541
TI  - Adjunctive color Doppler ultrasonography in second-trimester transabdominal
      amnioinfusion.
AB  - Transabdominal amnioinfusion improves the diagnostic accuracy of ultrasonography
      in pregnancies complicated by second-trimester oligohydramnios. Needle
      localization may be difficult because of patient obesity or the absence of an
      acoustic window. The two cases presented demonstrate that color Doppler imaging
      facilitates amnioinfusion by visualizing the injection jet of free-flowing
      infusate, confirming intraamniotic needle placement.

PMID- 9539542
TI  - Change in male proportion of newborn infants in Japan.

PMID- 9539543
TI  - Use of antibiotics to prevent preterm birth.

PMID- 9539544
TI  - Fetal ductus arteriosus constriction, indomethacin, and gestational age.

PMID- 9539545
TI  - Radical hysterectomy: current management guidelines.

PMID- 9539546
TI  - Never cite sight unseen.

PMID- 9539547
TI  - Estrogen-androgen hepatotoxicity?

PMID- 9539548
TI  - Endometrial cancer represents a contraindication for classic intrafascial
      supracervical hysterectomy by laparoscopy.

PMID- 9539549
TI  - Factor V Leiden and its relevance in patients with recurrent abortions.

PMID- 9539550
TI  - Antenatal factors in relation to neonatal outcome in preterm delivery.

PMID- 9539551
TI  - Symphysiotomy.

PMID- 9539552
TI  - Inferences from symphysiotomy experience.

PMID- 9539553
TI  - Emergency symphysiotomy--too little, too late.

PMID- 9539554
TI  - Should interstitial thermometry be used for deep hyperthermia?

PMID- 9539555
TI  - Impaired DNA repair as assessed by the "comet" assay in patients with thyroid
      tumors after a history of radiation therapy: a preliminary study.
AB  - PURPOSE: Patients with a history of head and neck irradiation in childhood are at
      risk to develop thyroid tumors. The aim of this study was to determine if an
      impairement of DNA strand breaks repair could account for this observation.
      METHODS AND MATERIALS: Circulating unstimulated lymphocytes of a group of 13
      patients who developed thyroid tumors after radiotherapy were submitted to the
      alkaline single-cell gel electrophoresis assay (SCGE or "comet" assay) after in
      vitro exposure to 2 and 5 Gy of gamma-rays. A control group of 8 healthy donors
      and 2 cases with a history of neck irradiation who did not develop a thyroid
      tumor were also analysed. The immediate response was compared to that observed
      after 15, 30, and 60 min of postexposure incubation periods. RESULTS: Induction
      of DNA strand breaks is a dose-dependent process. The SCGE assay parameters did
      not differ significantly between patients and controls immediately (t=0) after
      irradiation at the two doses used. As compared to healthy donors, a slower
      kinetics of repair was found in the patients. The proportion of residual damage
      at 60 min postirradiation was significantly (p < 0.01) higher in patients than in
      controls, at both doses analysed. Flow cytometric analysis of apoptosis and p53
      protein status studied before and after irradiation showed no apparent
      relationship with the repair capacity. CONCLUSION: This preliminary study
      suggests that a subgroup of patients who develop thyroid tumors after a history
      of irradiation are partially defective in the late restitution of in vitro
      radiation-induced DNA strand breaks. This deficiency could be a predisposing
      factor to radiation-associated thyroid tumorigenesis. Detection of susceptible
      individuals using the simple and rapid comet assay, especially children receiving
      radiotherapeutic treatment, may allow a preventive surveillance for radiation
      associated epithelial thyroid tumor development.

PMID- 9539556
TI  - The value of ultrasound with ultrasound-guided fine-needle aspiration biopsy
      compared to computed tomography in the detection of regional metastases in the
      clinically negative neck.
AB  - PURPOSE: Head and neck oncologists have not reached consensus regarding the role
      of contemporary imaging techniques in the evaluation of the clinically negative
      neck in patients with head and neck squamous cell carcinoma (HNSCC). The purpose
      of the present study was to compare the accuracy of ultrasound with guided fine
      needle aspiration biopsy (UGFNAB) and computed tomography (CT) in detecting lymph
      node metastasis in the clinically negative neck. METHODS AND MATERIALS: Sixty
      four neck sides of patients with HNSCC were examined preoperatively by
      ultrasound/UGFNAB and CT at one of five participating tertiary care medical
      centers. The findings were correlated with the results of histopathologic
      examination of the neck specimen. RESULTS: Ultrasound with guided fine-needle
      aspiration biopsy was characterized by a sensitivity of 48%, specificity of 100%,
      and overall accuracy of 79%. Three cases had nondiagnostic aspirations using
      UGFNAB and were excluded. CT demonstrated a sensitivity of 54%, specificity of
      92%, and overall accuracy of 77%. UGFNAB detected two additional metastases not
      visualized on CT, whereas CT detected no metastases not seen on UGFNAB. The
      results of UGFNAB were similar between the participating centers. CONCLUSIONS:
      Approximately one half of the clinically occult nodal metastases in our patient
      group were identified by both CT and UGFNAB. Overall, UGFNAB and CT demonstrated
      comparable accuracy. The sensitivity of CT was slightly better than UGFNAB, but
      the latter remained characterized by a superior specificity. The results of CT
      and UGFNAB did not appear to be supplementary. The choice of imaging modality for
      staging of the clinically negative neck depends on tumor site, T-stage, and
      experience and preference of the head and neck oncologist. If CT is required for
      staging of the primary tumor, additional staging of the neck by UGFNAB does not
      provide significant additional value.

PMID- 9539557
TI  - Mucosa-adhesive water-soluble polymer film for treatment of acute radiation
      induced oral mucositis.
AB  - PURPOSE: To examine the usefulness and safety of a mucosa-adhesive water-soluble
      polymer film (AD film) containing anesthetics and antibiotics for the treatment
      of acute radiation-induced oral mucositis. MATERIALS AND METHODS: To prepare AD
      films, 600 mg of hydroxy-propyl-cellulose was dissolved in ethyl alcohol, and
      mixed with a solution containing tetracaine, ofloxacine, miconazole, guaiazulene,
      and triacetin. The gel obtained was dried to form 30 translucent round sheets (20
      mg per sheet) of 7.5 cm in diameter and 0.2 mm in thickness. The AD film showed
      excellent adhesive and coating properties when placed on wet oral mucosa. From
      1993 to 1994, we used the AD film in 25 patients with acute radiation-induced
      oral mucositis, in an attempt to alleviate their pain and prevent secondary oral
      infection. All patients had received definitive radiotherapy for oral carcinoma.
      Intensity and duration of oral pain from mucositis, relief rates at rest and
      while eating, and presence of bacterial and/or fungal infection were compared
      with those of 27 patients treated with topical anesthetics (viscous lidocaine,
      Xylocaine and/or general systemic analgesics from 1990 to 1992 (NonAD Group).
      RESULTS: The intensity of oral pain was the same in the two groups. The mean
      duration of pain of the AD film Group (10 days) was significantly shortened
      compared with the NonAD Group (15 days). The rates of complete pain relief at
      rest and while eating of the AD film Group were statistically higher than those
      of the NonAD Group: 82% vs. 44%, and 68% vs. 22%, respectively. No secondary
      bacterial or fungal infections were observed in the AD film Group, whereas 4
      cases of documented infections were found in the NonAD Group. No acute or chronic
      adverse effects of AD film were observed during the 3-year follow-up period. The
      rates for local control of oral carcinoma and overall survival, at the end of the
      follow-up period, were 96% and 87% for the AD film Group vs. 92% and 85% for the
      NonAD Group, respectively. CONCLUSION: The AD film, containing topical
      anesthetics and antibiotics, proved useful to alleviate pain due to acute
      radiation-induced oral mucositis, maintain good peroral feeding, and prevent
      secondary oral infections, without inducing adverse reactions.

PMID- 9539558
TI  - Concurrent cisplatin, prolonged oral etoposide, and vincristine plus chest and
      brain irradiation for limited small cell lung cancer: a phase II study of the
      Southwest Oncology Group (SWOG-9229).
AB  - PURPOSE: The primary objectives of the study were to evaluate the efficacy and
      safety of prolonged oral (PO) etoposide as part of cisplatin-based chemotherapy
      plus concurrent chest/brain irradiation induction, followed by CAV consolidation,
      in the treatment of patients with limited-stage small cell lung cancer (SCLC-LD)
      within a cooperative group setting. METHODS AND MATERIALS: Fifty-six eligible
      patients with SCLC-LD received three 28-day cycles of cisplatin 50 mg/m2 i.v.
      (days 1, 8; 29, 36; and 57, 64), PO etoposide 50 mg/m2 (days 1-14, 29-42, and 57
      70), and vincristine 2 mg i.v. (days 1, 29, and 57). Thoracic irradiation (TRT)
      was administered at 1.8 Gy in 25 daily fractions to a total dose of 45 Gy via an
      AP:PA arrangement, to begin concomitantly with induction chemotherapy.
      Prophylactic cranial irradiation (PCI) was started on day 15 of induction
      therapy. Fifteen daily fractions of 2.0 Gy were administered to the entire brain
      to a total dose of 30 Gy to finish at approximately the same time as TRT. Two 21
      day cycles of consolidation cyclophosphamide 750 mg/m2 i.v., doxorubicin 50 mg/m2
      i.v., and vincristine 2 mg i.v. (all on days 1 and 22), were given beginning on
      day 106 or week 16, from the start of induction therapy. RESULTS: Among 56
      eligible patients, 93% had SWOG performance status 0-1. All had adequate organ
      function and had not received prior therapy. The overall confirmed response rate
      was 46%, including 16% complete responders and 30% partial responders. After a
      minimum follow-up duration of 17 months, the Kaplan-Meier median progression-free
      (PFS) and overall survival (OS) were 10 and 15 months, respectively. Two-year
      survival is 28%. Only 28 of 56 patients (50%) completed chemotherapy per
      protocol, while 52 of 56 patients (93%) completed radiation per protocol. Eleven
      patients (20%) discontinued secondary to toxicity and two patients died from
      treatment. The major toxicity was hematologic. The two deaths were secondary to
      infection. Of the nonhematologic toxicities, there were 10 cases of pulmonary
      fibrosis (including one Grade 3) and six cases of pneumonitis (including one
      Grade 3). CONCLUSION: Concomitant chemoradiation with oral etoposide as part of a
      platinum-based chemotherapy and TRT induction regimen is toxic. The CR rate is
      not better than our prior best group-wide experience. The progression-free and
      overall survival are similar to published trials utilizing short-course i.v.
      etoposide. As in chemotherapy for extensive-stage SCLC, there is no apparent
      advantage to prolonged exposure to etoposide, and toxicity resulted in an
      inferior therapeutic index compared to programs with shortened exposure.

PMID- 9539559
TI  - Neoadjuvant concurrent chemoradiotherapy followed by definitive high-dose
      radiotherapy or surgery for operable thoracic esophageal carcinoma.
AB  - PURPOSE: A prospective clinical trial was undertaken to investigate the
      feasibility of concurrent chemoradiotherapy for esophageal carcinomas. MATERIALS
      AND METHODS: Between June 1989 and May 1996, forty patients with operable
      squamous cell carcinoma of the thoracic esophagus (Stage 0 to III: UICC 1987),
      ages 45 to 78 years (mean: 64), were enrolled in a study of neoadjuvant
      concurrent chemoradiotherapy followed by definitive high-dose radiotherapy (CRT
      group) or surgery (CRT-S group). Neoadjuvant chemoradiotherapy consisted of 44 Gy
      in 40 fractions for 4 weeks (2.2 Gy/2 Fr/day) through 10-MVX rays, with 2 courses
      of cisplatin (80-100 mg/body, mean: 60 mg/m2, Day 1, bolus injection) and 5
      fluorouracil (500-1000 mg/body/day, mean: 400 mg/m2, Days 1-4, continuous
      infusion). After completion of neoadjuvant chemoradiotherapy, an intermediate
      clinical response was assessed by barium swallow, esophagoscopy with/without
      biopsy, EUS in most cases, thoracic and upper abdominal CT scan, and cervical US.
      Definitive chemoradiotherapy was performed in patients when regression of more
      than 75% was evident (CRT Group), and esophageal resection was indicated in those
      who remained at less than 75% (CRT-S Group). In CRT Group, a cumulative dose of
      60-70 Gy for Tis, T1 and 65-75 Gy for T2-T4 tumor with high-dose-rate
      intraluminal brachytherapy and a total of 3 courses of chemotherapy were planned.
      In CRT-S Group, intraoperative radiotherapy for abdominal lymphatic system and
      postoperative supraclavicular irradiation were added. RESULTS: At the time of
      intermediate assessment, complete response (CR) was observed in 16 patients, a
      partial response (PR) in 22, and no change (NC) in 2. Thirty responding patients
      (CR, 16; PR, 14) entered the CRT Group, and 10 nonresponding patients (PR, 8; NC,
      2) were followed by surgery (CRT-S Group). Radiotherapy was completed
      satisfactorily, but chemotherapy was suspended in 26 patients (65%) because of
      acute toxicity. Clinical CR rate at the completion of treatment showed 90% in CRT
      Group, and pathologic CR rate 10% in CRT-S Group. The overall median survival was
      45 months, survival at 1, 2, and 3 years being 100%, 72%, and 56%, respectively.
      Local-regional failure was observed in 7 patients (all in CRT Group), distant
      failure in 6 (3 in CRT Group, 3 in CRT-S Group) and local-regional with distant
      failure in 1 (CRT Group). Four patients with local-regional recurrence in the CRT
      Group were salvaged by surgery. Overall survival at 2 and 3 years for CRT vs. CRT
      S Group was 72%, 64% vs. 75%, 38%, respectively. No treatment-related mortality
      was observed. The rate of the 'esophagus conservation' was 65% (Stage 0: 1 of 1,
      100%; Stage I: 11 of 12, 92%; Stage II: 8 of 17, 47%; Stage III: 6 of 10, 60%).
      CONCLUSION: Our results demonstrated that almost all early disease (Stage 0-I)
      and about half of advanced disease (Stage II-III) could be conserved, their
      esophagus treated by the multidisciplinary approach centering on high-dose
      radiotherapy and concurrent chemotherapy.

PMID- 9539560
TI  - Accelerated hyperfractionated radiation therapy and concurrent 5
      fluorouracil/cisplatin chemotherapy for locoregional squamous cell carcinoma of
      the thoracic esophagus: a phase II study.
AB  - PURPOSE: To improve the poor prognosis of patients with locoregional esophageal
      squamous cell cancer, we used concurrent accelerated hyperfractionated radiation
      therapy (ACC HFX RT) and chemotherapy (CHT). MATERIAL AND METHODS: Between
      January 1988 and June 1993, 28 patients were treated with ACC HFX RT with 1.5 Gy
      twice daily, to a total dose of 54 Gy concurrently with 5-fluorouracil (5-FU)
      (300 mg/m2, days 1-5) and cisplatin (CDDP) (10 mg/m2, days 1-5), both given
      during weeks 1 and 4 of the ACC HFX RT course. Following the ACC HFX RT/CHT, two
      additional courses of 5-FU (500 mg/m2, days 1-5) and CDDP (20 mg/m2, days 1-5)
      were both given during weeks 7 and 10. The median age and Eastern Cooperative
      Oncology Group performance status were 62 and 1, respectively. The American Joint
      Committee on Cancer (AJCC) stage was I in 12 patients, II in 10, and III in 6.
      RESULTS: The median survival time was 26 months, and the 5-year survival rate was
      29%. The rates at 5 years for freedom from relapse, locoregional recurrence, and
      distant metastasis were 29%, 61%, and 45%, respectively. Univariate analysis
      revealed that performance status, stage, weight loss, tumor length, and tumor
      location influenced survival, while age and sex did not. The most frequent acute
      high-grade (3 or 4) toxicities were esophagitis and leukopenia, seen in 50% and
      39% of patients, respectively. Late high-grade toxicity was infrequent. There
      were no treatment-related deaths. CONCLUSION: The results of this study compare
      favorably with those of previous studies, albeit of relatively high incidence of
      acute high-grade toxicity. Further studies are warranted to compare its efficacy
      with other approaches.

PMID- 9539561
TI  - Preoperative chemoradiation for extraperitoneal T3 rectal cancer: acute toxicity,
      tumor response, and sphincter preservation.
AB  - PURPOSE: To evaluate whether or not an intermediate dose of preoperative external
      radiation therapy intensified by systemic chemotherapy could improve the tumor
      response, sphincter preservation, and tumor control. METHODS AND MATERIALS:
      Between March 1990 and December 1995, 83 consecutive patients with resectable
      extraperitoneal adenocarcinoma of the rectum were treated with preoperative
      chemoradiation: bolus i.v. mitomycin C (MMC), 10 mg/m2, Day 1 plus 24-h
      continuous infusion i.v. 5-fluorouracil (5FU) 1000 mg/m2, Days 1-4, and
      concurrent external beam radiotherapy (37.8 Gy). All but 2 patients had T3
      disease. Surgery was performed 4-6 weeks after the end of chemoradiation.
      RESULTS: Total Grade 3-4 acute toxicity during chemoradiation was observed in 11
      (13%) patients: hematological Grade 3 toxicity was recorded in 8 (10%) patients,
      and Grade 4 toxicity was recorded in 2 (2%) patients. Grade 3 diarrhea was seen
      in 2 (2%) patients. No patient had major skin or urological acute toxicity. Two
      patients had no surgery: 1 died before surgery from septic complications after
      Grade 4 hematological toxicity; 1 refused surgery and is still alive after 6
      years. There was no postoperative mortality and the overall perioperative
      morbidity rate was 25%. The analysis of tumor response involved 81 patients.
      Overall, 9% (7) of 81 patients had a complete pathologic response. Comparing the
      stage at the diagnostic workup with the pathologic stage, tumor downstaging was
      observed in 46 (57%) patients. We had 7 (9%) pT0, 5 (6%) pT1, 33 (41%) pT2, and
      36 (44%) pT3. Nodal status downstaging was detected in 46 patients (57%). No
      evidence of nodal involvement was observed in 59 patients (73%). The incidence of
      tumor response was affected significantly by the number of quarters of rectal
      circumference involved (p = 0.03) and, marginally, by the length of the tumor (p
      = 0.09). The distance between the lower pole of the tumor and the anorectal ring
      had no influence. Of the patients, 63 (78%) had a sphincter-saving surgical
      procedure. In 12 (44%) of 27 patients candidate for an APR, the sphincter was
      preserved, as it was in 19 (95%) of 20 probable candidates. Lengthening of the
      distance between the anorectal ring and the lower pole of the tumor > 20 mm was
      observed in 21 patients (26%). Of 63 patients, 4 (6%) had moderate soilage after
      the sphincter-saving procedure. CONCLUSION: Preoperative combined modality
      therapy seems to afford some potential advantages in nonrandomized trials:
      patients are able to tolerate higher chemotherapy doses and they experience a
      lower acute toxicity. Tumor downstaging and resectability rates are high;
      sphincter preservation is feasible. Larger T3 tumors remained less influenced by
      this treatment; thus, taking into account the low toxicity rate recorded, a more
      aggressive schedule should be applied in these resectable tumors.

PMID- 9539562
TI  - Conservative management of rectal adenocarcinoma by radiotherapy.
AB  - PURPOSE: The aim of this study was to analyze the experience of Centre GF Leclerc
      for conservative and curative treatment by radiotherapy of low rectal cancer.
      PATIENTS AND METHODS: A total of 151 patients received radiotherapy alone for
      rectal adenocarcinoma with curative intent. They were clinically staged according
      to size (T1 < 3 cm, and T2 > 3 cm) and depth of infiltration (A=superficial, and
      B=impaired mobility and T3 fixed). Over the past 6 years, rectal ultrasound (US)
      has been used systematically, compared with computed tomographic scan and
      magnetic resonance imaging when needed. Intracavitary contact X ray was given to
      129 patients (69%), and brachytherapy in 45 of 151. External radiotherapy was
      used in 34 cases (22.5%). RESULTS: Complete response was obtained in 93%. Local
      failures were observed in 50 cases (28%); two occurred in pelvic nodes after
      intracavitary X rays. Size (tumors > 3 cm) and alteration of mobility
      significantly influenced the rate of local failure (p=0.009 and 0.007). The
      addition of external radiotherapy in patients with poor prognostic factors
      improved the local control rate. A total of 39 patients with recurrence were
      amenable to salvage surgery. After salvage treatment, the local control rate was
      82% with unlimited follow-up. The 5-year actuarial survival rate was 57%, with a
      specific survival of 66%. There was no difference in local control or survival
      according to differentiation of the tumors and distance between anal margin and
      the inferior level of the lesion. Severe late effect (grade 3) was 3.8%. The
      sphincter preservation was obtained in 104 of 124 cases (84%). The sphincter
      function was judged to normal in 102 of 104 patients (98%). CONCLUSION:
      Intracavitary contact X ray is the treatment of choice for clinical Stage T1A
      rectal tumors. External radiotherapy significantly improved the results of
      treatment of tumors > 3 cm. Clinical staging and transrectal ultrasound allows a
      safe selection of indications. Radiotherapy alone may be proposed for selected
      cases as an alternative to mutilating surgery for small rectal adenocarcinoma.

PMID- 9539563
TI  - Customized gynecologic interstitial implants: CT-based planning, dose evaluation,
      and optimization aided by laparotomy.
AB  - PURPOSE: Interstitial perineal implants may be utilized to deliver a high local
      radiation dose in the treatment of advanced gynecologic malignancies. Lack of
      knowledge of the precise anatomic relationships between the implant and the
      target and critical organs may limit efficacy and increase complication risks.
      Computed tomography (CT)-based planning, dose evaluation, and optimization of
      customized interstitial implants, aided by laparotomy, have been developed to
      overcome these limitations. METHODS AND MATERIALS: Twenty patients with locally
      advanced gynecologic malignancies treated between May 1990 to October 1996 with
      external irradiation and one or two implants. Interstitial implants were
      performed when intracavitary brachytherapy was judged to be inadequate or when
      the response to external radiation and an intracavitary implant was not
      satisfactory. Customized interstitial implants were planned using preimplantation
      CT to determine catheter angles and paths that best implanted the target while
      avoiding pelvic bones and organs. Laparotomy aimed at lysing bowel adhesions,
      placement of omental carpet, and refining needle placement. Postimplantation CT
      was used for loading optimization and dose evaluation. RESULTS: Catheter angles
      15-25 degrees were found to adequately implant anteriorly laying targets while
      avoiding pubic bones and bladder. Adhesiolysis of bowel loops from the vaginal
      apex was required in patients with prior hysterectomy. Small modifications in
      catheter placements were made during laparotomy in all implants. Postimplantation
      CTs showed deviations of the catheter positions compared with the planning CTs
      and were essential in determining target and organ doses and loading
      optimization. At a median follow-up of 42 months (range: 9-80 months), local
      control rate is 55% and disease-free survival 40%. Late complications occurred in
      2 of 11 of patients without local recurrence. CONCLUSIONS: CT-based planning,
      loading optimization, and dose evaluation of customized implants improve
      radiation dose delivery. Laparotomy enhances implant accuracy and safety. Local
      tumor control rate is still unsatisfactory. It reflects the shortcomings of
      technical advances alone in poor prognosis tumors like those selected for this
      series.

PMID- 9539564
TI  - The clinical implications of hydronephrosis and the level of ureteral obstruction
      in stage IIIB cervical cancer.
AB  - PURPOSE: There are two criteria for the diagnosis of Stage IIIB cervical cancer
      in the FIGO staging system: tumor fixation to the pelvic side wall and/or the
      presence of hydronephrosis due to tumor. However, we often encounter
      hydronephrosis without tumor fixed to the pelvic side wall or the level of
      ureteral obstruction not corresponding to the main tumor mass in the pelvis. The
      clinical implication of these phenomena remains unclear. We investigated the
      Stage IIIB population treated at the Mallinckrodt Institute of Radiology and
      hypothesized that, if hydronephrosis presents without tumor fixation to the
      pelvic side wall or if the level of ureteral obstruction is above the main pelvic
      tumor mass, it most likely resulted from external compression of ureter(s) by
      enlarged lymph nodes and, consequently, a worse outcome is expected. METHODS AND
      MATERIALS: From 1959 to 1989, there were 297 patients with Stage IIIB cervical
      cancer who received definitive radiation therapy at the Mallinckrodt Institute of
      Radiology and were assessable for the presence of hydronephrosis and the level of
      ureteral obstruction. There were 281 patients who presented with tumor fixed to
      the pelvic side wall, and 62 of them were associated with concurrent
      hydronephrosis. An additional 16 patients presented with hydronephrosis without
      tumor fixation to the pelvic side wall. Among these 78 documented cases of
      hydronephrosis, the level of ureteral obstruction was above the true pelvis in 39
      patients, and below the true pelvis in the other 39. Radiation therapy was
      individualized according to tumor extension and configuration; para-aortic lymph
      nodes were not routinely treated except in patients with clinical evidence of
      nodal metastasis. RESULTS: The progression-free survival (PFS) at 5 years was 35%
      in 62 patients with hydronephrosis and tumor fixed to the pelvic side wall vs.
      43% in 213 patients with tumor fixed to the pelvic side wall only (p=0.12).
      However, PFS at 5 years decreased to 23% in 16 patients who presented with
      hydronephrosis without tumor fixation to the pelvic side wall (p < 0.001). When
      the level of ureteral obstruction was investigated, 5-year PFS was 39% vs. 22%,
      respectively, for the obstruction below vs. above the true pelvis (p=0.02). The
      majority of patients with ureteral obstruction above the true pelvis died of
      distant metastasis. CONCLUSIONS: The additional presence of hydronephrosis did
      not significantly worsen the PFS among Stage IIIB patients with tumor fixation to
      the pelvic side wall. However, hydronephrosis without tumor extending to the
      pelvic side wall or the level of ureteral obstruction above the true pelvis was
      associated with poor outcome due to a significant increase in distant failure. We
      propose that this population be separated from current Stage IIIB classification.

PMID- 9539565
TI  - Radiotherapy options for localized prostate cancer based upon pretreatment serum
      prostate-specific antigen levels and biochemical control: a comprehensive review
      of the literature.
AB  - PURPOSE: To review all the available radiotherapy (RT) literature on localized
      prostate cancer treatment where serum prostate-specific antigen (PSA) levels were
      used to both stratify patients and evaluate outcome and determine if any
      conclusions can be reached regarding an optimal radiotherapeutic management for
      this disease. METHODS AND MATERIALS: A MEDLINE search was conducted to obtain all
      articles in English on prostate cancer treatment employing RT from 1986-1997.
      Studies were considered eligible for review only if they met all the following
      criteria: 1) pretreatment PSA values were recorded and grouped for subsequent
      evaluation, 2) posttreatment PSA values were continuously monitored, 3)
      definitions of biochemical control were stated, and 4) the median follow-up was
      given. RESULTS: Of the 246 articles identified, only 20 met the inclusion
      criteria; 4 using conformal external beam RT, 8 using conventional external beam
      RT, and 8 using interstitial brachytherapy (4 using a permanent implant alone, 3
      combining external beam RT with a permanent implant, and 1 combining a conformal
      temporary interstitial implant boost with external beam RT). No studies using
      neutrons (with or without external beam RT) or androgen deprivation (combined
      with external beam RT) were identified where patients were stratified by
      pretreatment PSA levels. Results for all therapies were extremely variable with
      the 3-5-year rates of biochemical control for patients with pretreatment PSA
      levels < or = 4 ng/ml ranging from 48 to 100%, for PSA levels >4 and < or = 10
      ng/ml ranging from 44 to 90%, for PSA levels >10 and < or = 20 ng/ml ranging from
      27 to 89%, and for PSA levels >20 ranging from 14 to 89%. The median Gleason
      score, T-stage, definition of biochemical control, and follow-up were
      substantially different from series to series. No RT option consistently produced
      superior results. CONCLUSIONS: When data are reviewed from studies using serum
      PSA levels to stratify patients and to evaluate treatment outcome, no
      consistently superior RT technique was identified. These data suggest that
      standard definitions of disease stage (combining clinical, pathologic, and
      biochemical criteria) and a common definition of biochemical cure (as developed
      by the American Society for Therapeutic Radiology and Oncology Consensus Panel)
      need to be adopted to evaluate treatment efficacy and advise patients on the most
      appropriate radiotherapeutic option for their disease.

PMID- 9539566
TI  - Timing of computed tomography-based postimplant assessment following permanent
      transperineal prostate brachytherapy.
AB  - PURPOSE: To establish the rate of resolution of prostatic edema following
      transperineal interstitial permanent prostate brachytherapy, and to determine the
      results and impact of timing of the postimplant assessment on the dose-volume
      relationship. METHODS AND MATERIALS: A series of 19 consecutive patients with
      early-stage adenocarcinoma of the prostate receiving transperineal interstitial
      permanent prostate brachytherapy, were enrolled in this study. Twelve received
      125I and seven received 103Pd. Postoperative assessment included a computed
      tomographic (CT) scan on postoperative days 1, 8, 30, 90, and 180. On each
      occasion, CT scans were performed on a GE helical unit at 3-mm abutting slices,
      15-cm field of view. Prostate volumes were outlined on CT scans by a single
      clinician. Following digitization of the volumes and radioactive sources, volumes
      and dose-volume histograms were calculated. The prostate volume encompassed by
      the 80% and 100% reference isodose volumes was calculated. RESULTS: Preimplant
      transrectal ultrasound determined volumes varied from 17.5 to 38.6 cc (median
      27.9 cc). Prostate volumes previously defined on 40 randomly selected postimplant
      CT scans were compared in a blinded fashion to a second CT-derived volume and
      ranged from -32% to +24%. The Pearson correlation coefficient for prostate CT
      volume reproducibility was 0.77 (p < 0.03). CT scan-determined volume performed
      on postoperative day 1 was an average of 41.4% greater than the volume determined
      by preimplant ultrasound. Significant decreases in average volume were seen
      during the first month postoperatively. Average volume decreased 14% from day 1
      to day 8, 10% from day 8 to day 30, 3% from day 30 to day 90, and 2% thereafter.
      Coverage of the prostate volume by the 80% isodose volume increased from 85.6% on
      postoperative day 1 to 92.2% on postoperative day 180. The corresponding increase
      in the 100% reference dose coverage of the prostate volume ranged from 73.1% to
      83.3% between postoperative days 1, and 180, respectively. CONCLUSIONS: Most of
      the prostatic edema induced by brachytherapy appears to resolve by postoperative
      day 30. Scans performed on postimplant day 30 appear to adequately describe the
      time-averaged dose coverage of the prostate. This suggests that waiting
      approximately 1 month to perform postimplant analysis gives the most accurate
      prostatic volume and, consequently, dosimetric description of the implant.

PMID- 9539567
TI  - The final report of the expert panel for the radiation oncology bone metastasis
      work group of the American College of Radiology.
AB  - BACKGROUND: In the United States, at least half of the patients who are
      irradiated are done so with palliative intent. The most common presentation is
      the patient with bone metastasis. However, because current scientific outcome and
      technology techniques are insufficient for the creation of guidelines, the
      American College of Radiology created a work group of experts to formulate
      appropriateness criteria for the irradiation of bone metastasis. METHOD: A
      MEDLINE search to help review the community practices was initiated. Twenty-five
      clinical vignettes were reviewed by a panel of experts. Recommendations for each
      vignette were prioritized and selected based on choices proposed by panel
      members. RESULT: Doses in the range of 20 Gy in 5 fractions, 30 Gy in 10
      fractions, or 35 Gy in 14 fractions are acceptable in most circumstances. Daily
      doses > 4.0 Gy were not commonly suggested. CIRCUMSTANCES: To determine optimal
      dose fractionation schemes, more emphasis needs to be put on the life expectancy
      of the patients. Rapid schedules are acceptable in patients with short life
      expectancy (i.e., < 3 months), but this hypothesis needs to be tested. Further
      research to better define the clinical indications of hemibody irradiation and
      strontium-89 is recommended.

PMID- 9539568
TI  - What is the role of radiation in the treatment of subfoveal membranes: review of
      radiobiologic, pathologic, and other considerations to initiate a multimodality
      discussion.
AB  - BACKGROUND: Single-dose-fraction conformal proton beam and multiple-fraction X
      ray dose schedules have been used to treat subfoveal neovascular membranes. All
      schedules successfully controlled membrane progression, stabilized vision in most
      patients, and increased visual acuity in some. Conformal protons also decreased
      the radiation dose to healthy tissues outside the designated volume (16 mm in
      diameter). It appears that radiation therapy could be useful and cost-effective,
      but neither the optimal time-dose schedule single or multiple dose fractions nor
      the type of radiation proton conformal beam or x-ray therapy are defined.
      METHODS: By means of an extensive literature survey, we reviewed the rationale
      for using radiation to treat subfoveal neovascularization, examined a paradigm of
      radiation interaction with tissue, reviewed the histopathology of neovascular
      membranes, and documented the role of growth factors in the pathophysiology of
      the disease. Accepting that the eye is an extracranial brain extension, and that
      its microvasculature has properties similar to brain microvessels, we reviewed
      the radiobiologic response of brain microvessels. We also revisited the
      controversy concerning the efficacy of single-dose-fraction vs. multifraction
      schedules. RESULTS: This paper outlines parameters within which radiation
      therapy's role might be defined, and proposes a clinical radiation-biology
      scoring program to evaluate radiation effects, based on the SOMA concept.
      CONCLUSION: A prospective, controlled clinical trial is feasible and is indicated
      to determine radiation therapy's role in managing the proliferative component of
      age-related macular degeneration.

PMID- 9539569
TI  - Use of the prone position in radiation treatment for women with early stage
      breast cancer.
AB  - PURPOSE: The prone position has been advocated for women with large pendulous
      breasts undergoing breast-conserving treatment with radiation therapy. However,
      there is no information in the literature regarding the coverage of the target
      volume with this technique. The purpose of this study was to evaluate the
      effectiveness of the prone treatment position in including at least the biopsy
      cavity with a 2-cm margin. METHODS AND MATERIALS: Eleven consecutive patients who
      underwent CT simulation in the prone position were included in this study.
      Patients underwent CT simulation in the prone position using a flat platform
      containing an aperture for the breast to hang through in a dependent fashion. CT
      slices were 5-mm thick taken at 3-mm intervals. The biopsy cavity was localized
      and outlined on sequential CT images using the surgical clips (when present) as
      well as the residual seroma. A 2-cm margin was included around the biopsy cavity
      to define the minimal target volume (mTV). Lateral fields were used for treatment
      planning. The beam arrangements were considered adequate if the mTV was totally
      included in the lateral fields. RESULTS: Median age of the patient population was
      55 years. Bra sizes ranged from 36A-44DD. The majority of patients had
      mammographically detected T1 lesions. Median volume of the biopsy cavity was 48
      cm3. Five of 11 (45%) patients underwent reexcision of the biopsy cavity, and 6
      of 11 (55%) had surgical clips placed in the biopsy cavity. Overall, 8 of 11
      (73%) patients did not have the entire mTV included in the lateral opposed
      tangential fields in the prone position. This was especially true in patients
      whose biopsy cavity extended down to the chest wall. There were no other clinical
      factors that could predict for the adequacy of coverage in the prone position.
      CONCLUSION: Special attention must be paid to the location of the surgical clips
      to determine the proximity of the biopsy cavity to the chest wall, or CT
      simulation should be performed to determine the exact location of the biopsy
      cavity prior to selecting patients with large pendulous breasts for treatment in
      the prone position.

PMID- 9539570
TI  - High-dose conformal radiotherapy influenced the pattern of failure but did not
      improve survival in glioblastoma multiforme.
AB  - BACKGROUND AND PURPOSE: Although glioblastoma multiforme is clearly radiation
      resistant, there is evidence of a dose-dependent response relationship. The
      purpose of the study was to evaluate the impact of higher dose by rotational
      multileaf collimator (MLC) conformal radiation therapy. MATERIALS AND METHODS:
      From 1984 to 1995, 38 consecutive cases with intracranial glioblastoma multiforme
      were treated using the rotational MLC conformal therapy. There were 25 men and 13
      women with a median age of 47 years (12-73 years, mean 46.5 years). Median
      Karnofsky performance score was 80 (30-100, mean 78.2). Median tumor volume was
      64 cc (8-800 cc, mean 110.3 cc). All underwent surgical intervention (only biopsy
      in 1, partial resection in 13, subtotal resection in 21, and gross total
      resection in 3). Radiation dose to was 60 to 80 Gy (median 68.5 Gy, mean 68.3 Gy)
      in 21 patients treated before 1990 and 90 Gy in the 17 patients thereafter.
      Biweekly i.v. chemotherapy was also administered for both arms. RESULTS: The 1
      year, 2-year, 5-year, and 10-year overall survival rates were 75%, 42%, 20%, and
      15%, respectively. Univariate analysis showed the initial tumor volume, residual
      tumor volume, and Karnofsky performance score were statistically significant
      factors for survival. Only the residual tumor volume was statistically
      significant by multivariate analysis. The 5-year survival rate of patients with
      residual tumors of 5 cc or less in volume was as good as 37%. Survival of the 90
      Gy Group appeared inferior to that of the Low-Dose Group, though no statistical
      difference was seen (the 3-year survival was 40% vs. 22%). Local failure was
      observed in 16 of the 19 recurrences in the Low-Dose Group, whereas it was
      observed in only 4 of the 13 recurrences in the 90-Gy Group. The difference in
      pattern of failure was statistically significant. Two patients of the High-Dose
      Group developed radiation necrosis and one died of it. CONCLUSIONS: The high-dose
      conformal radiotherapy did not improve survival in the disease, but did change
      the pattern of failure.

PMID- 9539571
TI  - Reirradiation of brain and skull base tumors with fractionated stereotactic
      radiotherapy.
AB  - PURPOSE: We evaluated the feasibility of fractionated stereotactic radiotherapy
      for small intracranial recurrences after conventional radiotherapy. METHODS AND
      MATERIALS: Nineteen patients who had initially undergone conventional
      radiotherapy to intracranial lesions, receiving a median total dose of 50 Gy in 5
      weeks, were retreated with stereotactic radiotherapy for their recurrences and
      received a median total dose of 42 Gy in seven fractions over 2.3 weeks. RESULTS:
      Of the 19 patients, 15 achieved local control 3-51 months after reirradiation. No
      patient suffered from acute reaction, but one patient with a history of extensive
      radiotherapy developed progressive radionecrosis 9 months after reirradiation.
      CONCLUSIONS: Fractionated stereotactic radiotherapy of intracranial recurrences
      appears to be effective in achieving in local control with negligible morbidity.
      We believe it merits further investigation in a prospective study.

PMID- 9539573
TI  - Enhancement of radiation response by paclitaxel in mice according to different
      treatment schedules.
AB  - PURPOSE: The aim of our study was to determine if paclitaxel could be used as a
      radiosensitizer in vivo. MATERIALS AND METHODS: Paclitaxel was tested as a single
      agent and combined with an X-ray treatment. Paclitaxel was administered i.p. in
      doses from 30 to 120 mg/kg b.w. to (C3D2F1) mice bearing spontaneous mammary
      carcinoma. Tumor growth delay (TGD) or tumor control dose (TCD50, radiation dose
      needed to induce local tumor control in 50% of irradiated animals) and moist
      desquamation dose (MDD50, radiation dose needed to induce serious moist
      desquamation in 50% of the non-tumor-bearing feet) were the endpoints. DNA flow
      cytometric analysis was performed. RESULTS: DNA analysis demonstrated a G2/M
      block of tumor cells and a depletion of cells in S phase, with a maximum at 24 h
      from paclitaxel administration. Administering paclitaxel, in graded doses, 15 min
      before a 10-Gy X-ray treatment resulted in a linear regression line, almost
      parallel to that with paclitaxel alone, with a growth delay of about 6 days. In
      contrast, varying the X-ray dose with a constant paclitaxel injection (45 mg/kg
      b.w.) treatment showed some degree of synergism as the linear regression curves
      diverged. Interval time and sequence between paclitaxel administration and a 10
      Gy X-ray treatment did not influence TGD. Protocols with paclitaxel at 30, 45, or
      60 mg/kg were combined with radiation treatments at various doses (from 10 to 65
      Gy). Values of TCD50 varied from 50.8 Gy for X-ray alone to 31.8 Gy for
      paclitaxel 60 mg/kg + X-ray. No differences were observed among MDD of different
      protocols. CONCLUSIONS: These results suggest that, under some conditions,
      paclitaxel combined with radiation can show superadditive effects and this result
      combined with the lack of severe normal tissue damage indicate that a favorable
      therapeutic gain can be obtained.

PMID- 9539572
TI  - Short intensive primary chemotherapy and radiotherapy in sporadic primary CNS
      lymphoma (PCL).
AB  - PURPOSE: To assess the efficacy and toxicity of combined modality therapy with
      short intensive primary chemotherapy in the treatment of primary CNS lymphoma
      (PCL). METHODS AND MATERIALS: Prospective study of 31 nonimmunodeficient patients
      with PCL treated with initial chemotherapy (13 shortened MACOP-B; and 18 modified
      MACOP with high dose methotrexate) followed by radiotherapy (whole brain and a
      boost). Patients were aged 18-72 years (median 51 years). Eight patients had
      positive CSF cytology of which one had spinal meningeal disease; one patient had
      vitreous involvement. RESULTS: The overall complete response (CR) rate after
      chemotherapy and radiotherapy was 69% (95% Confidence Interval: 49-84%). At a
      median follow-up of 24 months (4 months to 10 years) median survival was 23
      months and 5-year survival 34%. Age, sex, performance status, number of lesions,
      CSF cytology, and extent of surgery were not of prognostic significance for
      survival on univariate analysis. Eleven patients developed mucositis (Grade 3+)
      and 21 hematological toxicity (Grade 3+) with 22 septicemic episodes in 15
      patients. Three patients developed dementia, one assumed to be treatment related,
      and two due to recurrent disease. CONCLUSION: The survival results of short
      intensive primary chemotherapy followed by radiotherapy are similar to the
      results of chemotherapy in Stage IV aggressive systemic non-Hodgkin's lymphoma,
      although the treatment was associated with high morbidity. The apparently
      favorable results when compared to radiotherapy alone may at least in part be due
      to selection of patients with good prognostic factors. To confirm the benefit of
      combined chemotherapy and radiotherapy over either of the two modalities alone
      requires evaluation in large prospective and ideally randomized studies.

PMID- 9539574
TI  - Radiobiological hypoxia in the KHT sarcoma: predictions using the Eppendorf
      histograph.
AB  - PURPOSE: To investigate whether electrode measurements of tumor oxygenation
      obtained under a range of different treatment conditions designed to alter the
      degree of tumor hypoxia could be correlated with estimates of radiobiological
      hypoxia measured under the same conditions. METHODS AND MATERIALS: Experiments
      were performed in restrained, nonanesthetized, female C3H/He mice, which had
      approximately 0.5 g KHT sarcomas growing intramuscularly in the hind limbs. The
      treatments used to modify tumor oxygenation status included breathing gas
      mixtures of varying oxygen content, altering tumor blood flow, and shifting the
      hemoglobin oxygen dissociation curve. Radiobiological hypoxic fraction was
      estimated using the paired survival curve assay, while electrode measurements of
      tumor oxygenation were obtained with an Eppendorf histograph. RESULTS: With the
      selected manipulations it was possible to vary the radiobiological hypoxic
      fraction in the tumors from approximately 1 to approximately 100% of the total
      viable cell population. Furthermore, these changes in radiation response were
      directly reflected in the changes in tumor oxygenation measurements made with the
      Eppendorf histograph. CONCLUSION: These findings suggest that in the KHT tumor
      model the Eppendorf electrode measurements could predict the response of the
      tumors to radiation as determined by the proportion of hypoxic cells.

PMID- 9539575
TI  - The development of a [211AT]-astatinated endoradiotherapeutic drug: part IV--late
      radiation effects.
AB  - PURPOSE: 6-[211At]-astato-MNDP is a high-LET endoradiotherapeutic drug that
      selectively targets to an oncogenically associated alkaline phosphatase isoenzyme
      expressed by certain tumors. A detailed histopathological study of the late
      tissue effects of its endogenous alpha-particle emissions has been carried out in
      a murine tumor model. MATERIALS AND METHODS: Thyroid-blocked male C57BI/10 mice
      bearing a s.c. transplanted rectal adenocarcinoma were treated with a single i.p.
      injection of 10-750 kBq 6-[211At]-astato-MNDP. Cured mice (131) were studied.
      Detailed autopsies and histological examinations were performed on all mice. The
      study was concluded after 756 days. RESULTS: Lymphoma, plasmacytoma, and
      intercurrent infections secondary to chronic pulmonary fibrosis were the most
      commonly found late manifestations of alpha-radiation exposure. Low grade B-cell
      non-Hodgkin's lymphoma occurred in 19 (24.7%) of 77 mice, 13-17 months after
      receiving 3.5-185 kBq 6-[211At]-astato-MNDP. The incidence of lymphoma alone and
      its latency was similar to that of the control population (23.3%). Treatment
      doses exceeding 200 kBq 6-[211At]-astato-MNDP, were associated with the
      development of soft tissue plasmacytoma in 7 (13%) of 54 mice, after 17-22
      months. Generalized debilitation and nonspecific infections supervening pulmonary
      fibrosis significantly contributed to the late morbidity and mortality observed
      in mice treated with 300-750 kBq 6-[211At]-astato-MNDP. Dosimetry has afforded
      LD50/360 and LD50/420 estimates of 12-14 and 10-12 Cobalt-Gray equivalent (CGyE),
      respectively, for chronic lung damage. There was no histological evidence of
      chronic radiation damage to other critical healthy tissues. Normal thyroid
      morphology was preserved. CONCLUSIONS: Dose activities of 6-[211At]-astato-MNDP
      exceeding 300 kBq, were associated an increased risk of tumor induction and
      development of varying degrees of chronic pulmonary fibrosis implicated in the
      onset of terminal intercurrent infections. Within the therapeutic dose range 55
      300 kBq 6-[211At]-astato-MNDP, mortality associated with the incidence of
      significant late radiation damage in critical normal tissues and latent
      carcinogenesis was less than 15%. Data from this murine model suggest that
      clinically relevant activities of 6-[211At]-astato-MNDP may be given without
      unacceptable toxicity.

PMID- 9539576
TI  - Hyperthermia enhances thermal-neutron-induced cell death of human glioblastoma
      cell lines at low concentrations of 10B.
AB  - PURPOSE: To examine the ability of pre- vs. post-irradiation hyperthermia to
      enhance the effectiveness of thermal neutrons to kill human glioblastoma cells.
      METHODS AND MATERIALS: Human glioblastoma cell lines, T98G, A7, A172, and U 87MG,
      were exposed to thermal neutrons from the Kyoto University Research (KUR) reactor
      or to 60Co gamma-rays. Hyperthermia was tested before and after irradiation of
      T98G (44 degrees C, 15 min) and A7 cells (44 degrees C, 40 min), and with
      different concentrations (0-30 ppm) of 10B-boric acid. The biological end point
      of all experiments was cell survival measured by a colony formation assay.
      RESULTS: The relative biological effectiveness (RBE) values of thermal neutrons
      for these cell lines compared with 60Co gamma-rays were 1.8-2.0 at their D(0)
      values. When T98G and A7 cells were heated after thermal neutron irradiation,
      there was a synergistic effect at low 10B concentrations (up to 5 ppm for T98G
      and up to 10 ppm for A7 cells). With high concentrations of boron (10-30 ppm for
      T98G and 20-30 ppm for A7 cells), hyperthermia and neutron irradiation interact
      additively rather than synergistically. There was no enhancement when cells were
      heated before thermal neutron irradiation. These results suggest that the
      radiosensitizing effect of hyperthermia may be attributed to partial inhibition
      of the repair of the potentially lethal damage caused by neutron irradiation.

PMID- 9539578
TI  - Practical limitations of interstitial thermometry during deep hyperthermia.
AB  - PURPOSE: Intratumor thermometry during hyperthermia treatment is considered
      important for several reasons. The morbidity that we experienced from
      interstitially placed catheters in deep-seated tumors gave reason to weigh the
      advantages and disadvantages against each other. METHODS AND MATERIALS: The
      available thermometry in 215 patients treated with hyperthermia for deep-seated
      tumors was analyzed with the aim to evaluate practically feasible intratumor
      measurements. The influence of intratumor measurements on the treatment procedure
      was assessed. RESULTS: Total 120 catheters were placed interstitially in 78
      patients. Over the years, the percentage of patients with interstitial
      thermometry decreased considerably. Forty-nine catheters could remain in place
      during the whole hyperthermia treatment series. The remaining catheters had to be
      removed for more or less severe complications, including one fatal event. In
      fact, the interstitial catheters caused the most severe treatment-related
      morbidity. During 188 of the total 859 treatments, at least one interstitial
      catheter was available for thermometry. Per treatment with catheter(s) in situ,
      the average number of intratumor measurement sites was 6.9. The value of
      interstitial thermometry for power steering during treatment, to both optimize
      intratumor temperature distribution and prevent toxicity, appeared limited. The
      mean volume of the tumors with interstitial thermometry was 314 cm3, SD 325. In
      relation to the large tumor volumes, the thermal dose parameters calculated from
      the available data is considered to be of limited value. CONCLUSION: In view of
      the possible severe complications and the limited clinical value of the
      information achieved by interstitially placed thermometry catheters, interstitial
      thermometry was not found to routinely benefit the individual patient.

PMID- 9539577
TI  - Short-term effects of early-acting and multilineage hematopoietic growth factors
      on the repair and proliferation of irradiated pure cord blood (CB) CD34+
      hematopoietic progenitor cells.
AB  - PURPOSE: Hematopoietic growth factor(s) (GF) may exert positive effects in vitro
      or in vivo on the survival of hematopoietic stem and progenitor cells after
      accidental or therapeutic total body irradiation. METHODS AND MATERIALS: We
      studied the clonogenic survival and DNA repair of irradiated (0.36, 0.73, and
      1.46 Gy) CD34+ cord blood (CB) cells after short-term incubation (24 h) with GFs.
      CD34+ cells were stimulated with basic fibroblast growth factor (bFGF), stem cell
      factor/c-kit ligand (SCF), interleukin-3 (IL-3), IL-6, leukemia inhibitory factor
      (LIF), and granulocyte-monocyte colony stimulating factor (GM-CSF) alone or in
      combination in short-term serum-free liquid suspension cultures (LSC) immediately
      after irradiation and then assayed for clonogenic progenitors. DNA repair was
      evaluated by analysis of DNA strand breaks using the comet assay. Survival of CFU
      GM, BFU-E, and CFU-Mix was determined and dose-response curves were fitted to the
      data. RESULTS: The radiobiological parameters (D[0] and n) showed significant
      GF(s) effects. Combination of IL-3 with IL-6, SCF or GM-CSF resulted in best
      survival for CFU-GM BFU-E and CFU-Mix, respectively. Combinations of three or
      more GFs did not increase the survival of clonogenic CD34+ cells compared to
      optimal two-factor combinations. The D[0] values for CFU-GM, BFU-E, and CFU-Mix
      ranged between 0.56-1.15, 0.41-2.24, and 0.56-1.29 Gy, respectively. As for
      controls, the curves remained strictly exponential, i.e., all survival curves
      were strictly exponential without any shoulder (extrapolation numbers n=1 for all
      tested GF(s). DNA repair capacity of CD34+ cells determined by comet assay, was
      measured before, immediately after irradiation, as well as 30 and 120 min after
      irradiation at 1 Gy. Notably, after irradiation the 2-h repair of cytokine
      stimulated and unstimulated CD34+ cells was similar. CONCLUSION: Our data
      indicate that increased survival of irradiated CB CD34+ cells after short-term GF
      treatment is mediated through proliferative GF effects on the surviving fraction
      but not through improved DNA repair capacity.

PMID- 9539579
TI  - Dosimetric verification of the dynamic intensity-modulated radiation therapy of
      92 patients.
AB  - PURPOSE: To verify that optimized dose distributions provided by an intensity
      modulated radiation therapy (IMRT) system are delivered accurately to human
      patients. METHODS AND MATERIALS: Anthropomorphic phantoms are used to measure
      IMRT doses. Four types of verification are developed for: I) system commissioning
      with beams optimized to irradiate simulated targets in phantoms, II) plans with
      patient-optimized beams directed to phantoms simulating the patient, III) patient
      phantom hybrid plans with patient-optimized beams calculated in phantom without
      further optimization, and IV) in vivo measurements. Phantoms containing
      dosimeters are irradiated with patient-optimized beams. Films are scanned and
      data were analyzed with software. Percent difference between verified and planned
      maximum target doses is defined as "dose discrepancy" (deltavp). The frequency
      distribution of type II deltavp from 204 verification films of 92 IMRT patients
      is fit to a Gaussian. Measurements made in vivo yield discrepancies specified as
      deltaivp, also fit to a Gaussian. RESULTS AND DISCUSSION: Verification methods
      revealed three systematic errors in plans that were corrected prior to treatment.
      Values of [deltavp] for verification type I are <2%. Type II verification
      discrepancies are characterized by a Gaussian fit with a peak 0.2% from the
      centroid, and 158 [deltavp] <5%. The 46 values of [deltavp] >5% arise from
      differences between phantom and patient geometry, and from simulation,
      calculation, and other errors. Values of [deltavp] for verification III are less
      than half of the values of [deltavp] for verification II. A Gaussian fit of
      deltaivp from verification IV shows more discrepancy than the fit of deltavp,
      attributed to dose gradients in detectors, and exacerbated by immobilization
      uncertainty. CONCLUSIONS: Dosimetric verification is a critical step in the
      quality assurance (QA) of IMRT. Hybrid Verification III is suggested as a
      preliminary quality standard for IMRT.

PMID- 9539580
TI  - Phantoms for IMRT dose distribution measurement and treatment verification.
AB  - BACKGROUND: The verification of intensity-modulated radiation therapy (IMRT)
      patient treatment dose distributions is currently based on custom-built or
      modified dose measurement phantoms. The only commercially available IMRT
      treatment planning and delivery system (Peacock, NOMOS Corp.) is supplied with a
      film phantom that allows accurate spatial localization of the dose distribution
      using radiographic film. However, measurements using other dosimeters are
      necessary for the thorough verification of IMRT. METHODS: We have developed a
      phantom to enable dose measurements using a cylindrical ionization chamber and
      the localization of prescription isodose curves using a matrix of
      thermoluminescent dosimetry (TLD) chips. The external phantom cross-section is
      identical to that of the commercial phantom, to allow direct comparisons of
      measurements. A supplementary phantom has been fabricated to verify the IMRT dose
      distributions for pelvis treatments. RESULTS: To date, this phantom has been used
      for the verification of IMRT dose distributions for head and neck and prostate
      cancer treatments. Designs are also presented for a phantom insert to be used
      with polymerizing gels (e.g., BANG-2) to obtain volumetric dose distribution
      measurements. CONCLUSION: The phantoms have proven useful in the quantitative
      evaluation of IMRT treatments.

PMID- 9539581
TI  - Clinical impact of implementing the recommendations of AAPM Task Group 43 on
      permanent prostate brachytherapy using 125I. American Association of Physicists
      in Medicine.
AB  - PURPOSE: To determine the clinical impact upon permanent interstitial prostate
      125I brachytherapy after conversion to AAPM Task Group 43 (TG 43) guidelines.
      METHODS: The value of quantities used in the calculation of dose from two
      institutions, Northwest Tumor Institute (NWTI) and Memorial Sloan-Kettering
      Cancer Center (MSKCC), which pioneered interstitial techniques for prostate
      brachytherapy were compared to those recently determined and published by TG 43
      of the American Association of Physicists in Medicine (AAPM). Using two different
      weighting schemes, the change in the commonly prescribed reference dose of 160 Gy
      was determined and found to be in agreement with that recently suggested. Volumes
      encompassed by the reference isodose surface were determined from a single source
      implant and a regularly distributed implant to show the effect of change in
      reference dose. A comparative analysis on 10 patients was performed to show how
      this change affected common implant quality descriptors and the effect of
      changing the calculation formalism without changing the reference dose. RESULTS:
      Both weighting schemes suggested a change in reference dose from 160 to 144 Gy.
      Single-source and distributed-source volumetric analysis confirmed this value.
      The effect on commonly used conformity and uniformity quantifiers for 10 implant
      patients was tabulated. CONCLUSION: Upon adopting the recommendations suggested
      by TG 43, institutions that perform permanent 125I prostate implants using
      calculation methods adapted from the NWTI or MSKCC should revise their treatment
      prescriptions from 160 to 144 Gy so that the doses delivered to patients remain
      unaffected. Institutions using other techniques to calculate dose should conduct
      an analysis similar to the one detailed here.

PMID- 9539582
TI  - Simple look-up table of optimized dwell time intervals using a high-dose-rate
      remote afterloader for endovascular irradiation.
AB  - PURPOSE: This article's objective is to develop a simple methodology deliver a
      uniform radiation dose to the wall of a narrow peripheral artery for preventing
      restenosis using a high-dose-rate (HDR) 192Ir remote afterloader. METHODS AND
      MATERIALS: Based upon published two-dimensional data such as anisotropy factors
      of an HDR 192Ir source calculated from the Monte-Carlo method, arterial wall
      doses at a close range from an HDR source may be easily calculated using the
      special formula suggested in Task Group Report No. 43 published by the American
      Association of Physicists in Medicine. An optimization procedure was used to
      calculate the optimized dwell times for delivering a uniform dose along arterial
      walls for various arterial diameters and lengths of lesions. RESULTS: Based on
      lengths of the stenosis and diameters of arteries or angioplasty balloons, a set
      of simple look-up tables for optimal dwell time intervals of endovascular
      radiation treatment have been developed for the MicroSelectron HDR remote
      afterloader. CONCLUSION: Doses for endovascular irradiation have been accurately
      calculated with anisotropy factors. For delivering uniform doses along the
      arterial wall, a set of look-up tables listed for optimal dwell times is
      available for the HDR remote afterloader.

PMID- 9539584
TI  - Endogenous heparin-like substances significantly impair coagulation in patients
      undergoing orthotopic liver transplantation.
AB  - Orthotopic liver transplantation (OLT) is associated with severe bleeding,
      especially after reperfusion of the grafted liver. Heparin released from the
      liver graft contributes to postreperfusion coagulopathy. Although patients with
      liver cirrhosis have increased levels of endogenous heparinoids, the role of
      these substances during liver transplantation is unclear. Therefore, we performed
      native and heparinase-modified thrombelastography (TEG) in 72 patients undergoing
      OLT. TEG was performed at skin incision, 10 min before and 10 min after clamping
      of the vena cava, 10 min before and 10 min after graft perfusion, and at the end
      of surgery. Heparinase-modified TEG compared with native TEG demonstrated heparin
      activity. In contrast to other investigations, we found significant heparin
      effects before reperfusion, although patients received no exogenous heparin.
      These heparin effects were greater in patients with cirrhosis compared with
      patients with cancer as the underlying disease leading to OLT. Administration of
      coagulation factors is the usual treatment of coagulopathies during OLT. The
      comparison of native versus heparinase-modified TEG can distinguish between
      heparin activity or coagulation factor deficiency as a cause of bleeding
      complications and provides a rational approach to the treatment of bleeding
      during OLT. IMPLICATIONS: Impaired coagulation function, contributed to by
      heparin or heparin-like substances, is frequently observed after reperfusion of a
      transplanted liver. This study demonstrates that a heparinase-modified
      thrombelastography can identify significant heparin effects in the absence of
      exogenous heparin administration in patients undergoing liver transplantation.

PMID- 9539583
TI  - A multicenter, randomized, blind comparison of amrinone with milrinone after
      elective cardiac surgery.
AB  - Amrinone and milrinone are phosphodiesterase inhibitors with positive inotropic
      effects useful for the treatment of ventricular dysfunction after cardiac
      surgery. Forty-four patients undergoing elective cardiac surgery at four centers
      received either amrinone (n = 22) or milrinone (n = 22) in a randomized, blind
      fashion. Immediately after separation from cardiopulmonary bypass (CPB), two
      bolus doses of either amrinone 0.75 mg/kg or milrinone 25 microg/kg were
      administered over 30 s, separated by 5 min. Hemodynamic measurements were
      recorded before each dose and at the end of the 10-min study. Both amrinone and
      milrinone increased the cardiac index (48% vs 52%, P = not significant [NS] for
      amrinone and milrinone, respectively). There was a small increase in mean
      arterial pressure (MAP) after amrinone administration (from 68 +/- 3 to 72 +/- 3
      mm Hg at 10 min, P < 0.05) with no significant change in MAP after milrinone
      administration. Central venous pressure was significantly higher in the amrinone
      group at baseline and 5 min (12 vs 10 mm Hg and 11 vs 10 mm Hg, respectively; P <
      0.05). Systemic and pulmonary vascular resistances decreased significantly and to
      a similar extent after either amrinone or milrinone administration. Phenylephrine
      was required in 11 of 22 patients receiving amrinone and in 11 of 22 patients
      receiving milrinone to maintain arterial blood pressure. The proportion of
      patients requiring an intravascular volume infusion (15 of 22 vs 17 of 22, P =
      NS) and the total fluid volume infused were similar (402 +/- 57 vs 350 +/- 49 mL,
      P = NS for amrinone and milrinone, respectively). Amrinone and milrinone seem to
      have similar hemodynamic effects after CPB, with the exception of blood pressure,
      although the need for vasopressor support of blood pressure did not differ.
      Selection between these two drugs may include nonhemodynamic considerations such
      as cost. IMPLICATIONS: Amrinone and milrinone are drugs that improve cardiac
      contraction. Their effects have never been directly compared in patients. We
      found that amrinone and milrinone produced similar hemodynamic effects in adult
      patients undergoing cardiac surgery. Choice between the two drugs can be based on
      nonhemodynamic considerations such as cost.

PMID- 9539585
TI  - Is there a better right-sided tube for one-lung ventilation? A comparison of the
      right-sided double-lumen tube with the single-lumen tube with right-sided
      enclosed bronchial blocker.
AB  - Anatomic variation between tracheal carina and the take-off of the right upper
      bronchus often makes the use of a right-sided double-lumen tube (R-DLT) or a
      single-lumen tube with right-sided enclosed bronchial blocker tube (R-UBB)
      (Univent) undesirable. This study compared the R-DLT with the R-UBB to determine
      whether there was any advantage of one over the other during anesthesia with one
      lung ventilation (OLV) for right-sided thoracic surgeries. Forty patients
      requiring right lung deflation were randomly assigned to one of two groups.
      Twenty patients received a right-sided BronchoCath double-lumen tube, and 20
      received a Univent tube with a bronchial blocker placed in the right mainstem
      bronchus. The following were studied: 1) time required to position each tube
      until satisfactory placement was achieved; 2) number of times that fiberoptic
      bronchoscopy was required (including one with the patient supine and one in
      lateral decubitus position); 3) number of malpositions after initial confirmation
      of tube placement; 4) time required until lung collapse; 5) surgical exposure;
      and 6) cost of tubes per case. No differences were found with any of these
      variables except that the cost of acquisition overall was greater for the R-UBB
      than for the R-DLT. No right upper lobe collapse was observed in the
      postoperative period in the chest radiograph in any of the patients studied. We
      conclude that either tube can be used safely and effectively for right-sided
      thoracic surgeries that require anesthesia for OLV. IMPLICATIONS: In this study,
      right-sided double-lumen tubes were compared with the Univent with right-sided
      bronchial blockers. The results indicate that either tube can be used for right
      sided thoracic surgery.

PMID- 9539586
TI  - Intraoperative torsade de pointes ventricular tachycardia and ventricular
      fibrillation during sevoflurane anesthesia.

PMID- 9539587
TI  - Preoperative prostaglandin E1 therapy in a patient with atrial septal defect and
      predominant right-to-left shunting.

PMID- 9539588
TI  - Use of the laryngeal mask airway in children with upper respiratory tract
      infections: a comparison with endotracheal intubation.
AB  - Several studies suggest that placement of an endotracheal tube (ETT) in a child
      with an upper respiratory infection (URI) increases the risk of complications.
      However, the development of the laryngeal mask airway (LMA) has provided
      anesthesiologists with an alternative means of airway management. This study was
      therefore designed to evaluate the use of the LMA in children with URIs and to
      compare it with the ETT. The study sample consisted of 82 pediatric patients (3
      mo to 16 yr of age) who presented for elective surgery with an URI. Patients with
      URIs were randomly allocated to receive either an ETT (n = 41) or a LMA (n = 41)
      and were followed for the appearance and severity of any perioperative
      complications. The two groups were similar with respect to age, gender,
      anesthesia and surgery times, number of attempts at tube placement, and
      presenting URI symptoms. There were no differences between groups in the
      incidence of cough, breath-holding, excessive secretions, or arrhythmias.
      Although one patient in the ETT group required a muscle relaxant for
      laryngospasm, the overall incidence of laryngospasm was similar between the two
      groups. There was, however, a significantly greater incidence of mild
      bronchospasm in the ETT group compared with the LMA group (12.2% vs 0%, P <
      0.05). The incidence of major arterial oxygen desaturation events (SpO2 <90%)
      during placement of the airway device was also significantly increased in the ETT
      group (12.5% vs 0%, P < 0.05). Furthermore, the total number of all episodes of
      respiratory complications, i.e., breath-holding, laryngospasm, bronchospasm, and
      major oxygen desaturation, was significantly greater in the ETT group (35 vs 19,
      P < 0.05). Despite this, all respiratory complications were easily managed, and
      there were no adverse sequelae. Although the risks associated with anesthetizing
      a child with an URI remain controversial, results from this study suggest that
      the LMA offers a suitable alternative to the ETT for use in children with URIs.
      IMPLICATIONS: This study compares the use of the laryngeal mask airway with the
      endotracheal tube for airway management in children with upper respiratory
      infections. Results suggest that if the decision is made to proceed with
      anesthesia for the child with an upper respiratory infection, then the laryngeal
      mask airway provides a suitable alternative to the endotracheal tube.

PMID- 9539589
TI  - Bacterial colonization and infection rate of continuous epidural catheters in
      children.
AB  - Continuous epidural infusions are widely used for postoperative analgesia in
      children. We prospectively studied the incidence of bacterial colonization of
      caudal and lumbar epidural catheters, as well as the incidence of serious
      systemic and local infection, in 210 children after short-term epidural
      analgesia. Using aseptic technique, epidural catheters were inserted into either
      the lumbar or the caudal epidural space based on the preferences of the
      anesthesia team and/or clinical indication. The integrity of the catheter and
      overlying transparent dressing site was evaluated by a member of the pediatric
      pain service at least once a day. The catheters were aseptically removed if the
      patient had a fever greater than 39 degrees C, if the dressing was compromised,
      or when epidural analgesia was no longer required. The subcutaneous portion of
      the catheter was semiquantitatively cultured. Cellulitis (erythema, swelling,
      purulent discharge, pustule formation, or tenderness) was diagnosed by
      examination of the epidural insertion site. The mean (+/- SD) age of patients in
      the caudal catheter group (n = 170) was 3 +/- 3 yr; their mean weight was 13 +/-
      11 kg. The mean (+/- SD) age of patients in the epidural catheter group (n = 40)
      was 11 +/- 4 yr; their mean weight was 36 +/- 23 kg. All catheters remained in
      place for 3 +/- 1 days (range 1-5 days). There was no serious systemic infection
      (meningitis, epidural abscess, or systemic sepsis). Of all epidural catheters,
      35% (73 of 210) were colonized. Gram-positive colonization was similar in caudal
      (25%; 43 of 170) and lumbar (23%; 9 of 40) catheters. Gram-negative organisms
      were cultured from 16% of the caudal catheters (27 of 170) and 3% of the lumbar
      catheters (1 of 40). In patients treated with caudal epidural catheters, children
      aged >3 yr were less likely to have colonized epidural catheters than younger
      children. Age did not affect the probability of developing cellulitis at the
      insertion site. Although patients aged <3 yr with caudal catheters had a slightly
      greater risk of cellulitis than children aged >3 yr (14% vs 9%), this association
      was very weak (P = 0.33). We observed that, despite bacterial colonization of
      caudal and lumbar epidural catheters, serious systemic and local infection after
      short-term epidural analgesia did not occur in our study. IMPLICATIONS:
      Continuous epidural infusions are widely used for postoperative analgesia in
      children. We found no serious systemic infections after short-term (3 days)
      continuous epidural analgesia in children.

PMID- 9539590
TI  - Left ventricular systolic and diastolic function is unaltered during propofol
      infusion in newborn swine.
AB  - Propofol is a cardiac depressant with minimal diastolic effects in the adult
      myocardium. Cardiac effects of propofol in the newborn are unknown. We examined
      hemodynamic variables and systolic and diastolic left ventricular function in 12
      newborn pigs exposed to propofol at three different infusion rates (7.5, 15, and
      30 mg x kg(-1) x h(-1)) in random order with a background of fentanyl (100 microg
      x kg(-1) x h(-1)). Left ventricular (LV) pressure (Plv) and LV anterior-posterior
      dimension, determined by sonomicrometry, were continuously monitored. Mean
      arterial pressure (MAP), heart rate (HR), and LV end-diastolic pressure (LVEDP)
      were determined at every infusion. Systolic function was assessed by the maximal
      pressure-time derivative (dP/dt(max)), the slope of the end-systolic pressure
      dimension relationship (ESP-D), and by the preload recruitable stroke work index
      (PRSWI). Diastolic function was assessed by relaxation indices, the minimal
      pressure-time derivative (dP/dt(min)) and the relaxation time constant (tau), and
      by a stiffness index, the slope of the EDP-D relationship. MAP decreased
      approximately 25%, from 75.9 +/- 15.6 to 56.3 +/- 14.8 mm Hg (P < 0.05) with
      propofol, with no dose effect. HR and LVEDP were unchanged from control. Both
      dP/dt(max) and dP/dt(min) decreased with propofol infusion, but load-independent
      indices of systolic function (ESP-D slope and PRSWI) and tau were unchanged.
      Diastolic stiffness was not affected with either 7.5- or 30-mg x kg(-1) x h(-1)
      infusions but decreased significantly from 0.27 +/- 0.18 mm Hg/mm at control to
      0.18 +/- 0.18 mm Hg/mm (P < 0.05) with propofol 15 mg x kg(-1) x h(-1). With this
      profile, propofol may be useful for the newborn requiring anesthesia.
      IMPLICATIONS: Most anesthetics depress heart function in the newborn. We examined
      both heart contraction and relaxation during anesthesia with propofol in newborn
      pigs. Propofol had minimal influence on heart function in this model at the doses
      studied. This may therefore be a useful anesthetic to test in the newborn human.

PMID- 9539591
TI  - Chloral hydrate sedation: the additive sedative and respiratory depressant
      effects of nitrous oxide.
AB  - The combination of chloral hydrate and nitrous oxide (N2O) is often used for
      sedation in pediatric dentistry. The purpose of this study was to determine the
      extent to which N2O increases the level of sedation and respiratory depression in
      children sedated with chloral hydrate. Thirty-two children, 1-9 yr, received
      chloral hydrate, 70 mg/kg (maximum 1.5 g), and then received N2O (30% and 50%).
      Hypoventilation (maximal PETCO2 > 45 mm Hg) occurred in 23 (77%) children during
      administration of chloral hydrate alone, in 29 (94%) breathing 30% N2O (P = 0.08
      versus control), and in 29 (97%) breathing 50% N2O (P = 0.05 versus control).
      Mean PETCO2 was increased during 30% (P = 0.007) and 50% (P = 0.02) N2O
      administration. Using chloral hydrate alone, 8 (25%) children were not sedated,
      10 (31%) were consciously sedated, and 14 (44%) were deeply sedated. Using 30%
      N2O, 2 children (6%) were not sedated, 0 were consciously sedated, and 29 (94%)
      were deeply sedated (P < 0.0001). Using 50% N2O, 1 child (3%) was not sedated, 0
      were consciously sedated, 27 (94%) were deeply sedated, and 1 (3%) had no
      response to a painful stimulus (P < 0.0001). We conclude that the addition of 30%
      or 50% N2O to chloral hydrate often causes decreases in ventilation and usually
      results in deep, not conscious, sedation in children. IMPLICATIONS: Pediatric
      sedation in the dental office often consists of nitrous oxide (N2O) after chloral
      hydrate premedication. We found that the addition of 30% or 50% N2O to chloral
      hydrate often causes decreases in ventilation and usually results in deep, not
      conscious, sedation in children.

PMID- 9539592
TI  - Mucormycosis supraglottitis on induction of anesthesia in an immunocompromised
      host.

PMID- 9539593
TI  - A comparison of the efficacy, safety, and patient satisfaction of ondansetron
      versus droperidol as antiemetics for elective outpatient surgical procedures. S3A
      409 and S3A-410 Study Groups.
AB  - Two identical, randomized, double-blind, placebo-controlled studies enrolled 2061
      adult surgical outpatients at high risk of postoperative nausea and vomiting
      (PONV) to compare i.v. ondansetron 4 mg with droperidol 0.625 mg and droperidol
      1.25 mg for the prevention of PONV. The antiemetic drugs or placebo were
      administered i.v. 20 min before the induction of anesthesia with a barbiturate
      compound, followed by maintenance with N2O/isoflurane/enflurane. Nausea, emetic
      episodes, adverse events, and patient satisfaction were analyzed for the 0 to 2 h
      and 0 to 24 h postoperative periods. In the 0 to 2 h postoperative period, there
      was a complete response (no emesis or rescue antiemetic) in 46% of subjects given
      placebo (P < 0.05 versus antiemetic groups), in 62% given ondansetron, in 63%
      given droperidol 0.625 mg, and in 69% given droperidol 1.25 mg (P < 0.05 versus
      ondansetron). In the 0 to 24-h postoperative period, there were no significant
      differences in complete response between the ondansetron and droperidol 0.625 or
      1.25 mg groups; all groups remained superior to placebo. The proportion of
      patients without nausea during the 0 to 24 h postoperative period was greater in
      the antiemetic groups compared with the placebo group; however, droperidol 1.25
      mg was more effective than ondansetron 4 mg or droperidol 0.625 mg (43% vs 29% or
      29%, respectively). Headache incidence was higher in the ondansetron group
      compared with either droperidol group. Patient satisfaction scores did not differ
      significantly among antiemetic treatment groups, although all were superior to
      placebo. In conclusion, all antiemetic treatment regimens were superior to
      placebo for the prevention of PONV in the immediate postoperative period;
      however, droperidol 1.25 mg was more efficacious than ondansetron during the
      early recovery period (0-2 h). There were no significant differences between
      ondansetron and either droperidol dose for emesis prevention during the 0 to 24 h
      postoperative period. IMPLICATIONS: More than 2000 patients at high risk of
      postoperative nausea and vomiting were given either placebo, ondansetron 4 mg, or
      droperidol 0.625 mg or 1.25 mg i.v. before the administration of general
      anesthesia. After surgery, the incidence of nausea, vomiting, medication side
      effects, and patient satisfaction were evaluated for 24 h. Droperidol 0.625 or
      1.25 mg i.v. compared favorably with ondansetron 4 mg i.v. for the prevention of
      postoperative nausea and vomiting after ambulatory surgery.

PMID- 9539594
TI  - Symptom distress and functional status changes during the first seven days after
      ambulatory surgery.
AB  - In this study, we describe changes in symptom distress and functional status 24
      h, 4 days, and 7 days after ambulatory surgery. Adult patients aged 18-64 yr, ASA
      physical status I-III, were studied. The General Symptom Distress Scale was used
      to score 11 general symptoms; scores range from 0 (no symptoms present) to 4
      (symptoms present, constant, cannot be ignored, and, in a 24-h period, remained
      distressing for more than half the time). The Functional Status Questionnaire was
      used to evaluate basic and intermediate activities of daily living. Procedure
      specific analyses of covariance were performed using multiple linear regression
      analyses. These models were used to obtain estimates of change while adjusting
      for preoperative index values of age, ASA physical status, type of anesthesia,
      and study site. Models for hernia (n = 41) and laparoscopy (n = 59) procedures
      used F statistics to test the overall significance of the model. Symptom distress
      persisted until the 7th postoperative day after ambulatory surgery. Patients
      experienced decreased functional status during the first 7 postoperative days,
      especially after hernia repair. Older laparoscopy patients tended to have more
      symptom distress and decreased functional status than younger patients. Only 22%
      of patients had returned to full- or part-time work by the 7th postoperative day.
      We conclude that although major morbidity is uncommon after ambulatory surgery,
      symptom distress and reduced functional status are common 7 days postoperatively.
      IMPLICATIONS: Previous studies of patient status after ambulatory surgery have
      focused on mortality, major morbidity, and unanticipated hospitalization. In this
      study, we examined clinically significant but less life-threatening patient
      outcomes. Important problems in ambulatory surgery are posed by complications
      that occur at home. Careful assessment of discharge criteria is important to
      avoid these problems in this growing patient population.

PMID- 9539595
TI  - The use of a selective axillary nerve block for outpatient hand surgery.
AB  - Although no guidelines concerning discharge criteria after axillary plexus block
      are available, many institutions consider recovery of motor function as a
      critical factor. With the midhumeral approach, the four main nerves of the upper
      extremity can be blocked separately using a peripheral nerve stimulator. The aim
      of this double-blind study was to block the radial (R) and musculocutaneous (MC)
      nerves with lidocaine, and the median (M) and ulnar (U) nerves with bupivacaine
      to recover motor function of the elbow and wrist more rapidly while maintaining
      long-lasting postoperative analgesia at the operative site. Patients undergoing
      surgery for Dupuytren's contracture were randomized into two groups in a double
      blind fashion: in the control group (n = 17), each of the four nerves was
      infiltrated with 10 mL of a mixture of 2% lidocaine and 0.5% bupivacaine, whereas
      in the selective group (n = 17), the R and MC nerves were blocked with 10 mL of
      2% lidocaine each and the M and U nerves were blocked with 10 mL of 0.5%
      bupivacaine each. Recovery of motor block was significantly faster in the
      selective group (231 +/- 91 vs 466 +/- 154 min). However, time to first sensation
      of pain was not different between groups (707 +/- 274 vs 706 +/- 291 min). In
      conclusion, this new approach at the midhumeral level enables the
      anesthesiologist to selectively administer local anesthetics on different nerves.
      IMPLICATIONS: In outpatients undergoing surgery for Dupuytren's contracture, a
      midhumeral block was used with the musculocutaneous and radial nerves blocked by
      lidocaine and the median and ulnar nerves blocked with bupivacaine. Recovery of
      motor function and time to discharge were shorter compared with patients who
      received the mixture on all four nerves.

PMID- 9539596
TI  - The effects of adding isoproterenol to 0.125% bupivacaine on the quality and
      duration of epidural analgesia in laboring parturients.
AB  - This study was conducted to determine the effects of adding isoproterenol to
      epidural bupivacaine and sufentanil on the quality and duration of analgesia
      during labor. In a double blind, randomized study, 80 women were divided into two
      groups, receiving three doses of 0.125% bupivacaine with 7.5 microg of sufentanil
      and either 12.5 microg of epinephrine (EPI group) or 5 microg of isoproterenol
      (ISO group). Contraction pain was measured using a 100-mm visual analog scale
      (VAS) before epidural analgesia, at 5-min intervals for 15 min after each
      epidural injection, and hourly thereafter. Overall, no significant differences
      were observed in VAS scores between the groups. However, in the ISO group, VAS
      scores at 10 and 15 min after the first and second administration were
      significantly lower than those in the EPI group. Analgesia after each
      administration lasted significantly longer in patients who received epinephrine.
      Because of the limited duration of analgesia in the ISO group, more patients in
      this group received a fourth epidural administration of 0.125% bupivacaine with
      epinephrine 1:800,000. In conclusion, the addition of isoproterenol to
      bupivacaine and sufentanil induces a faster onset of analgesia and reduces the
      duration of analgesia compared with bupivacaine with sufentanil and epinephrine.
      Therefore, it is preferable to use isoproterenol only once, as a test dose, after
      the placement of the epidural catheter. IMPLICATIONS: We analyzed the quality and
      duration of analgesia in laboring women after they received bupivacaine and
      sufentanil combined with isoproterenol or epinephrine epidurally. We found that
      the addition of isoproterenol to bupivacaine and sufentanil induces a faster
      onset of analgesia and reduces the duration of analgesia.

PMID- 9539597
TI  - Inhaled prostaglandin E1 for treatment of acute lung injury in severe multiple
      organ failure.
AB  - Acute lung injury is characterized by hypoxemia due to pulmonary
      ventilation/perfusion-mismatching. I.v. administered prostaglandin E1 (PGE1), a
      vasodilator with a high pulmonary clearance, has been studied in acute lung
      injury. Inhalation of the vasodilators nitric oxide and prostacyclin improved
      oxygenation by selective dilation of the pulmonary vasculature in ventilated lung
      areas. In the present study, PGE1 inhalation was used for treatment of acute lung
      injury. Fifteen patients with acute lung injury defined as PaO2/fraction of
      inspired oxygen (FIO2) <160 mm Hg were treated with PGE1 inhalation in addition
      to standard intensive care. The drug was continuously delivered via a pneumatic
      nebulizer. Acute physiology and chronic health evaluation system II and multiple
      organ failure scores were (mean +/- SEM) 33 +/- 2 and 10 +/- 0.3, respectively.
      Inhaled PGE1 was administered for 103 +/- 17 h at a dose of 41 +/- 2 microg/h.
      The PaO2/FIO2 ratio increased from 105 +/- 9 to 160 +/- 17 mm Hg (P < 0.05) and
      to 189 +/- 25 mm Hg (P < 0.05) after 4 h and 24 h, respectively. PGE1 inhalation
      decreases in mean pulmonary artery pressure and central venous pressure were not
      statistically significant. Mean arterial pressure, pulmonary capillary wedge
      pressure, cardiac output, and heart rate remained unchanged. Intensive care unit
      mortality was 40%. The present data suggest that inhaled PGE1 is an effective
      therapeutic option for improving oxygenation in patients with acute lung injury.
      Whether inhaled PGE1 will increase survival in acute lung injury should be
      investigated in a controlled prospective trial. IMPLICATIONS: In patients with
      severe acute lung injury and multiple organ failure, inhaled prostaglandin E1
      improved oxygenation and decreased venous admixture without affecting systemic
      hemodynamic variables. Controlled clinical trials are warranted.

PMID- 9539598
TI  - The relationship of soluble adhesion molecule concentrations in systemic and
      jugular venous serum to injury severity and outcome after traumatic brain injury.
AB  - Adhesion molecules control the migration of leukocytes into tissue after injury.
      This may result in further cellular damage. We hypothesized that altered serum
      concentrations of soluble intercellular adhesion molecule (sICAM)-1 and soluble L
      selectin (sL-selectin) after traumatic brain injury would correlate with injury
      severity and neurological outcome. We investigated serum concentrations of sICAM
      1 and sL-selectin in 22 patients with traumatic brain injury admitted to the
      intensive care unit. The Glasgow Coma Scale (GCS) score and Injury Severity Score
      were recorded. Paired arterial and jugular venous blood samples were taken on
      admission and 24, 48, and 96 h after injury. Mean systemic and jugular venous
      concentrations of sICAM-1 were normal on admission but became significantly
      increased by 96 h (P = 0.018). sL-selectin concentrations of injured patients
      were markedly below those of controls at all time points (P < 0.001). There were
      no significant differences between jugular venous and arterial concentrations of
      either sICAM-1 or sL-selectin. Serum sICAM-1 was significantly related to
      neurological outcome (P < 0.001) and to the GCS score (P < 0.001). These changes
      in adhesion molecule expression after acute brain injury may be important in the
      pathophysiology of secondary injury. The highly significant relationship between
      serum sICAM-1 and neurological outcome suggests that the inflammatory response to
      injury may be detrimental. Drugs that antagonize the actions of the adhesion
      molecules may have a role in therapy after traumatic brain injury. IMPLICATIONS:
      This observational study shows that there is a strong association between soluble
      intercellular adhesion molecule-1 in serum and poor neurological outcome after
      traumatic brain injury. This suggests that inflammation after brain injury may
      worsen the prognosis and that therapies directed against this inflammation may
      prove useful.

PMID- 9539599
TI  - The vascular effects of topical and intravenous alpha2-adrenoceptor agonist
      clonidine on canine pial microcirculation.
AB  - To assess the direct cerebrovascular effects of clonidine, we investigated the
      pharmacological responses of pial vessels to its topical and i.v. administration
      using a cranial window. Forty-six dogs anesthetized with pentobarbital had the
      cranial window implanted. We administered six different concentrations of
      clonidine (10(-8), 10(-7), 10(-6), 10(-5), 10(-4), 10(-3) mol/L) dissolved in
      artificial cerebrospinal fluid under the window and measured the pial arterial
      and venous diameters. After pretreating pial vessels with either yohimbine, an
      alpha2-adrenoceptor antagonist, or glibenclamide, an adenosine triphosphate
      sensitive K+-channel blocker, their action was examined after applying clonidine.
      We also evaluated the effects of i.v. clonidine (5 microg/kg) on pial vascular
      tone. Topical clonidine produced significant constriction of the pial large and
      small arteries and veins in a concentration-dependent manner (P < 0.05).
      Yohimbine abolished the clonidine-induced pial arterial (large P < 0.005; small P
      < 0.0005) and venous constriction (large and small P < 0.0001). Glibenclamide
      potentiated the clonidine-induced pial arterial constriction (P < 0.05). I.v.
      clonidine did not cause significant changes in pial arteries, but it caused
      significant constriction of small veins. These were associated with a significant
      decrease in heart rate and an increase in serum potassium level and glucose
      concentration. In the present study, we demonstrate that the topical application
      of clonidine constricts both pial arterial and venous vessels in a concentration
      dependent manner and suggest that mechanisms of such action are caused by the
      activation of alpha2-adrenoceptors and adenosine triphosphate-sensitive K+
      channels, whereas i.v. clonidine constricts only pial small veins. IMPLICATIONS:
      In this study, we describe the direct and i.v. effects of clonidine on pial
      vessels using a cranial window in anesthetized dogs. The topical application of
      clonidine constricts pial vessels. This is mediated by the activation of alpha2
      adrenoceptors and adenosine triphosphate-sensitive K+-channels. I.v. clonidine
      constricts only pial small veins.

PMID- 9539600
TI  - Isoflurane and pentobarbital reduce the frequency of transient ischemic
      depolarizations during focal ischemia in rats.
AB  - Repetitive transient ischemic depolarizations (IDs) during focal cerebral
      ischemia are thought to contribute to ischemic damage. Isoflurane and
      pentobarbital reduce injury (versus the nonanesthetized state) after focal
      cerebral ischemia. The mechanism by which these drugs reduce injury is not known.
      This protective effect might be mediated by a reduction in the number of IDs. We
      measured the frequency of IDs during focal cerebral ischemia in animals
      anesthetized with isoflurane or pentobarbital and compared it with that in
      N2O/fentanyl anesthetized animals and in animals in which the N-methyl-D
      aspartate receptor antagonist MK801 (dizocilpine) was given. Focal cerebral
      ischemia was induced by the occlusion of the middle cerebral artery for a period
      of 2 h. Cortical infarct volumes were determined after 3 h of reperfusion by
      image analysis of 2,3,5-triphenyl tetrazolium-stained coronal brain sections. The
      infarct volume was significantly greater in the N2O/fentanyl group than in the
      other three groups. Infarct volumes in the isoflurane, pentobarbital, and MK801
      groups were similar. The frequency of IDs was significantly greater in the
      N2O/fentanyl group than in the other three groups, and was the least in the MK801
      group. There was a direct correlation between the number of IDs and the volume of
      tissue injury. The data indicate that the protective effect of isoflurane and
      pentobarbital might, in part, be determined by their ability to reduce IDs during
      focal ischemia. However, the observation that the infarct volume was similar in
      the MK801, isoflurane, and pentobarbital groups, despite a greater frequency of
      IDs in the latter two groups, suggests that mechanisms other than a simple
      reduction in the number of IDs probably also play a role in anesthetic-mediated
      cerebral protection. IMPLICATIONS: Transient ischemic depolarizations during
      focal ischemia contribute to brain injury. Both isoflurane and pentobarbital
      reduced the frequency of these depolarizations. Isoflurane- and pentobarbital
      mediated reduction in the frequency of depolarizations might, in part, mediate
      the previously documented neuroprotective effect of these drugs.

PMID- 9539601
TI  - The impact of postoperative pain on the development of postoperative delirium.
AB  - We performed a prospective observational study to examine the role of
      postoperative pain and its treatment on the development of postoperative
      delirium. Pain was measured in direct patient interviews using a visual analog
      scale (VAS) and was assessed for pain at rest, pain with movement, and maximal
      pain over the previous 24 h. Postoperative delirium was diagnosed during these
      interviews by using the confusion assessment method (CAM) and/or by using data
      from the medical record and the hospital's nursing intensity index. The method of
      postoperative analgesia, type of opioid, and cumulative opioid dose were also
      recorded. After controlling for known preoperative risk factors for delirium
      (age, alcohol abuse, cognitive function, physical function, serum chemistries,
      and type of surgery), higher pain scores at rest was associated with an increased
      risk of delirium over the first 3 postoperative days (adjusted risk ratio 1.20, P
      = 0.04). Pain with movement and maximal pain were not associated with delirium.
      Method of postoperative analgesia, type of opioid, and cumulative opioid dose
      were not associated with an increased risk of delirium. We conclude that more
      effective control of postoperative pain reduces the incidence of postoperative
      delirium. IMPLICATIONS: We performed daily interviews in a large population of
      patients undergoing noncardiac surgery to measure their level of pain and
      development of delirium. We found an association between higher pain levels at
      rest and the development of delirium. Our results suggest that better control of
      postoperative pain may reduce this serious complication.

PMID- 9539602
TI  - Epidural verapamil reduces analgesic consumption after lower abdominal surgery.
AB  - In this double-blind study, we administered lumbar epidural bupivacaine or
      bupivacaine plus verapamil to investigate the possible role of the calcium
      channel blocker, verapamil, in postoperative pain. One hundred patients (ASA
      physical class I or II) scheduled for lower abdominal surgery were randomly
      assigned to one of four groups. Group 1 received 10 mL of 0.5% epidural
      bupivacaine injected 15 min before incision, followed by 10 mL of epidural normal
      saline 30 min after incision. Group 2 received 10 mL of epidural normal saline
      injected before incision, followed by 10 mL of 0.5% epidural bupivacaine 30 min
      after incision. Group 3 received 10 mL of 0.5% epidural bupivacaine plus 5 mg of
      verapamil injected before incision, followed by 10 mL of epidural normal saline
      30 min after incision. Group 4 received the same drugs as Group 3, in the reverse
      order. Pain and mood numeric rating scores, sedation scores, Prince Henry scores,
      patient-controlled cumulative postoperative analgesic consumption, and the
      incidence of side effects were assessed 2, 6, 12, 24, and 48 h after the
      operation in each group. Cumulative postoperative analgesic consumption in Groups
      3 and 4 was significantly lower (P < 0.05) than that in Groups 1 and 2 24 and 48
      h after surgery. There were no differences in the pain, mood, and sedation scores
      and the incidence of side effects among the four groups. We conclude that
      epidural verapamil decreases postoperative pain, possibly by interfering with
      normal sensory processing and by preventing the establishment of central
      sensitization. IMPLICATIONS: Calcium plays an important role in pain physiology
      at the spinal cord level. We examined the effect of bupivacaine plus verapamil
      (calcium channel blocker) and of bupivacaine alone. We demonstrated that the
      combination, administered epidurally, resulted in less postoperative analgesic
      consumption than bupivacaine alone.

PMID- 9539603
TI  - The dose-response relationship of ketorolac as a component of intravenous
      regional anesthesia with lidocaine.
AB  - Ketorolac (K) is a useful addition to lidocaine for i.v. regional anesthesia
      (IVRA). However, the minimal dose of K that is effective for this purpose has not
      been established. We added 0, 5, 10, 15, 20, 30, and 60 mg of K to 0.5% lidocaine
      IVRA for either carpal tunnel release or tenolysis. Pain was assessed in the
      postanesthesia care unit by using a visual analog scale. The duration of
      analgesia (time to first request for pain relief) and the use of Tylenol No. 3
      tablets (T3) were measured. A linear dose-response relationship was observed
      between the dose of K and the duration of analgesia (r = 0.988) up to 20 mg of K.
      Similarly, the number of T3 tablets used was inversely related to the dose of K
      (r = 0.960) over the same range. There were no significant differences among the
      groups who received 20, 30, or 60 mg of K. We conclude that 20 mg of K is the
      optimal dose for inclusion with 0.5% lidocaine for IVRA under the conditions of
      our study. IMPLICATIONS: The antiinflammatory drug ketorolac is a useful addition
      to lidocaine for i.v. regional anesthesia. This study showed that 20 mg of
      ketorolac is equally effective as 60 mg in this context. However, smaller doses
      provided less effective pain relief, and a linear dose-response relationship was
      demonstrated.

PMID- 9539604
TI  - The effect of prior dural puncture on cerebrospinal fluid sufentanil
      concentrations in sheep after the administration of epidural sufentanil.
AB  - Sufentanil is a highly lipid soluble opioid that provides potent analgesia when
      administered in the subarachnoid space. Unfortunately, the penetration of
      sufentanil into the cerebrospinal fluid (CSF) after epidural administration is
      poor, and limits its effectiveness for epidural analgesia. Dural puncture may
      enhance the movement of epidural sufentanil into the subarachnoid space and
      increase its effectiveness. To determine whether the administration of epidural
      sufentanil adjacent to a dural puncture results in significantly greater CSF
      concentrations, 18 adult ewes were studied. Animals in the control group had an
      epidural catheter placed at the superior border of the pelvis without dural
      puncture. Animals in the study group had an epidural catheter placed, followed by
      a dural puncture performed using an 18-gauge Touhy needle. The dural puncture was
      performed one interspace cephalad to the epidural catheter. One hour after dural
      puncture, each animal received a loading dose of 0.35 microg/kg of sufentanil (5
      microg/mL) through the epidural catheter, followed by an infusion of epidural
      sufentanil 0.15 microg x kg(-1) x h(-1) for a period of 4 h. After 4 h, CSF was
      sampled from a site one interspace caudad to the epidural catheter as well as at
      the cisterna magna. The mean CSF concentration of sufentanil at the level of the
      pelvis for animals with a dural puncture was 12.1 +/- 3.0 ng/mL compared with 1.8
      ng/mL in controls with intact dura. Sufentanil concentrations at the cisterna
      magna were below the level of detection (0.08 ng/mL) for all animals in both
      groups. We conclude that an 18-gauge dural puncture significantly increases
      movement of sufentanil from the epidural to the intrathecal space. This increase
      in sufentanil concentration at the level of the pelvis was not associated with
      detectable levels of sufentanil at the brainstem. IMPLICATIONS: This study
      addresses the effect of dural puncture on spinal fluid concentrations of
      sufentanil after epidural administration. A sheep model was used to measure drug
      concentrations in the spinal fluid at the levels of the pelvis and brainstem
      after epidural administration. Dural puncture significantly enhanced movement of
      sufentanil into the spinal fluid at the level of the pelvis, but brainstem
      concentrations were below the level of detection. Analgesic concentrations of
      spinal sufentanil in the clinical setting, as well as brainstem concentrations
      associated with respiratory depression, have yet to be defined.

PMID- 9539605
TI  - Cardiovascular and central nervous system effects of intravenous levobupivacaine
      and bupivacaine in sheep.
AB  - Commercially available bupivacaine is an equimolar mixture of R(+)- and S(-)
      bupivacaine. S(-)-bupivacaine (i.e., levobupivacaine) is currently undergoing
      preclinical evaluation. Cross-over studies with i.v. levobupivacaine and
      bupivacaine were conducted in two groups of seven conscious sheep. Doses were
      chosen to avoid convulsions (smaller dose 6.25-37.5 mg/min) or to be potentially
      toxic (larger dose 75-200 mg/3 min). In subconvulsive doses, both drugs produced
      similar time- and dose-dependent depression of left ventricular systolic
      contractility (dP/dt(max)). Convulsions occurred consistently with > or = 75 mg
      of bupivacaine and > or = 100 mg of levobupivacaine, producing an abrupt reversal
      of dP/dt(max) depression. Subconvulsive doses produced minor cardiovascular
      effects on heart rate and blood pressure, whereas both were increased by
      convulsions. Cardiac output and myocardial blood flow were decreased with larger
      doses of both drugs. Doses > 75 mg of bupivacaine or > 100 mg of levobupivacaine
      induced QRS widening and ventricular arrhythmias, but significantly fewer and
      less deleterious arrhythmias were induced by levobupivacaine. Three animals died
      after 150, 150, and 200 mg of bupivacaine from the sudden onset of ventricular
      fibrillation. These doses of levobupivacaine produced nonfatal arrhythmias that
      automatically returned to sinus rhythm. We conclude that levobupivacaine could
      offer a greater margin of clinical safety than bupivacaine. IMPLICATIONS:
      Levobupivacaine comprises 50% of commercially available bupivacaine and is being
      considered for use in its own right. Local anesthetics can cause toxicity to the
      cardiovascular and central nervous systems. As a part of a preclinical evaluation
      of levobupivacaine, this study compared the toxic effects of levobupivacaine and
      bupivacaine in sheep.

PMID- 9539606
TI  - Systemic and regional pharmacokinetics of levobupivacaine and bupivacaine
      enantiomers in sheep.
AB  - Commercially available bupivacaine is an equimolar mixture of R(+)- and S(-)
      bupivacaine. S(-)-bupivacaine (levobupivacaine) is the subject of current
      clinical evaluation. We conducted partial cross-over systemic and regional
      pharmacokinetic studies of i.v. bupivacaine (12.5-200 mg) and levobupivacaine
      (6.25-200 mg) in ewes. Enantiospecific analysis of blood drug concentration-time
      data and of regional myocardial and brain drug mass balance data indicated that
      (a) there was a higher mean total body clearance of R(+)-bupivacaine than of S(-)
      bupivacaine (as previously reported); (b) there were no differences in the
      systemic pharmacokinetics of S(-)-bupivacaine whether administered alone or as a
      component of bupivacaine; (c) there was no evidence of dose-dependent
      pharmacokinetics with either enantiomer; (d) for both enantiomers, mean
      calculated myocardial tissue concentrations of 1%-4% dose occurred between 3 and
      5 min. Mean brain concentrations of 0.2%-1% dose occurred between 2 and 4 min
      after the administration of bupivacaine but between 4 and 5 min after the
      administration of levobupivacaine. There was no evidence that systemic toxicity
      induced by these local anesthetics significantly modified their pharmacokinetics,
      and there was no evidence of an enantiomer-enantiomer pharmacokinetic interaction
      for bupivacaine. IMPLICATIONS: Levobupivacaine comprises 50% of commercially
      available bupivacaine and is being considered for use in its own right. As a part
      of its preclinical evaluation, this study considered whether levobupivacaine
      behaved kinetically in the body in the same way as when administered as a
      component of bupivacaine.

PMID- 9539607
TI  - Arterial and pulmonary arterial concentrations of the enantiomers of bupivacaine
      after epidural injection in elderly patients.
AB  - Bupivacaine HCl is a 50:50 racemic mixture of the levo [S(-)] and dex [R(+)]
      enantiomers. The R(+) enantiomer exhibits greater cardiac tissue binding and
      toxicity. To determine whether the lung exhibits selective uptake of one of the
      enantiomers of bupivacaine, we measured pulmonary artery and radial artery blood
      concentrations of the two enantiomers after a lumbar epidural injection of 20 mL
      of 0.75% bupivacaine in 10 elderly patients undergoing one-stage bilateral total
      knee arthroplasty. Significantly lower concentrations of R(+) than S(-) were
      noted in both pulmonary artery and arterial blood. Both enantiomers were absorbed
      by the lung to a similar extent within the first 5 min after epidural injection
      (extraction ratio approximately equal to 0.1 or 10%). Mean time of maximal
      concentration (Tmax) was 6 min. In 3 of the 10 patients, Tmax occurred in 1-3
      min. We conclude that the lung absorbs both the R(+) and S(-) enantiomers of
      bupivacaine to a similar extent after epidural injection and that this is of
      doubtful clinical significance. This study also suggests that peak concentrations
      of bupivacaine may occur earlier after epidural injection in certain elderly
      patients than previously believed. IMPLICATIONS: In the first 5 min after
      epidural injection, approximately 10% of the local anesthetic bupivacaine was
      absorbed by the lung. Absorption of the two enantiomers (mirror images) of
      bupivacaine were similar. Lung absorption of bupivacaine is unlikely to influence
      local anesthetic toxicity.

PMID- 9539608
TI  - The effects of verapamil and nimodipine on bupivacaine-induced cardiotoxicity in
      rats: an in vivo and in vitro study.
AB  - The purpose of this in vivo and in vitro study was to compare the effects of
      verapamil or nimodipine pretreatment on bupivacaine-induced cardiotoxicity. In
      the in vivo study, the dose-response curve for the 50% lethal dose (LD50) of
      bupivacaine was determined for rats. Two separate groups of rats were pretreated
      with i.v. verapamil 150 microg/kg (n = 35) or i.v. nimodipine 200 microg/kg (n =
      35). Each pretreatment group was then subdivided into four groups of at least
      four rats each. Three minutes after pretreatment, bupivacaine was administered to
      each of four groups in doses of 2.5, 3.0, 3.25, and 3.5 mg/kg, respectively. Both
      verapamil and nimodipine pretreatment increased the LD50 and 95% confidence
      intervals for bupivacaine and increased survival. In the in vitro study, the
      effects of verapamil or nimodipine perfusion on bupivacaine cardiotoxicity
      (negative chronotropic, negative inotropic, and arrhythmogenic effects) and
      coronary perfusion pressure (CPP) were investigated in isolated, perfused rat
      heart preparations. Depression of heart rate, contractile force, and CPP, and the
      incidence of arrhythmias caused by bupivacaine alone were similar to those caused
      by bupivacaine after verapamil pretreatment. In contrast, bupivacaine induced
      less negative chronotropic effects (P < 0.05, paired t-test) and arrhythmias (P <
      0.05, chi2 analysis) after nimodipine pretreatment. The results of this study
      demonstrate that both verapamil and nimodipine pretreatment decrease bupivacaine
      induced cardiotoxicity in vivo, whereas only nimodipine pretreatment decreased
      bupivacaine-induced cardiotoxicity and arrhythmias in vitro. IMPLICATIONS: In
      this experimental study consisting of two stages (in vivo and in vitro), we
      compared the effects of two calcium channel-blocking drugs (verapamil and
      nimodipine) on bupivacaine toxicity. Bupivacaine is a local anesthetic frequently
      used in clinical practice, and cardiotoxicity is one of its severe side effects.
      Verapamil and nimodipine were both effective in decreasing bupivacaine
      cardiotoxicity in this rat model.

PMID- 9539609
TI  - Comparison of ketamine and dextromethorphan in potentiating the antinociceptive
      effect of morphine in rats.
AB  - We compared the efficacy of two clinically available drugs with N-methyl-D
      aspartate receptor antagonist properties, dextromethorphan and ketamine, in
      potentiating morphine-induced antinociception. Ketamine alone at 0.3-3 mg/kg had
      no effect on the hot plate test and at 10 mg/kg caused sedation/motor deficits.
      The antinociceptive effect of 5 mg/kg morphine was slightly enhanced by 1 mg/kg,
      but not 0.3 or 3 mg/kg, ketamine. Dextromethorphan alone at 45 mg/kg had no
      effect, but at 60 mg/kg caused sedation/motor deficit. At 15-45 mg/kg,
      dextromethorphan significantly and dose-dependently increased the magnitude and
      duration of morphine-induced antinociception. Dextromethorphan also potentiated
      morphine at doses that, by themselves, did not cause antinociception (1-2 mg/kg).
      IMPLICATIONS: Dextromethorphan was more effective than ketamine in potentiating
      morphine-induced antinociception. Dextromethorphan may thus be the drug of choice
      for testing the interactions between N-methyl-D-aspartate antagonists and
      morphine clinically.

PMID- 9539611
TI  - Epidural anesthesia and gastrointestinal motility.

PMID- 9539610
TI  - Antinociceptive potentiation and attenuation of tolerance by intrathecal co
      infusion of magnesium sulfate and morphine in rats.
AB  - N-methyl-D-aspartate (NMDA) antagonists, such as MK801, delay the development of
      morphine tolerance. Magnesium, a noncompetitive NMDA antagonist, reduces
      postoperative morphine requirements. The present study was designed to evaluate
      the effects of intrathecal co-administration of magnesium sulfate with morphine
      on antinociceptive potentiation, tolerance, and naloxone-induced withdrawal
      signs. Magnesium sulfate (40-60 microg/h) co-administration for 7 days, similar
      to MK801 (10 nmol/h), prevented the decline in antinociceptive response compared
      with morphine (20 nmol/h). Magnesium sulfate (60 microg/h) produced no
      antinociception, but co-infused with morphine (1 nmol/h), it resulted in
      potentiated antinociception compared with morphine throughout the 7-day period.
      Probe morphine doses after 7-day infusions demonstrated a significantly greater
      50% effective dose value for morphine 1 nmol/h (109.7 nmol) compared with saline
      (10.9 nmol), magnesium sulfate 60 microg/h (10.9 nmol), and magnesium sulfate 60
      microg/h plus morphine 1 nmol/h (11.2 nmol), which indicates that magnesium had
      delayed morphine tolerance. Morphine withdrawal signs after naloxone
      administration were not altered by the co-infusion of magnesium sulfate.
      Cerebrospinal fluid magnesium levels after intrathecal magnesium sulfate (60
      microg/h) for 2 days increased from 17.0 +/- 1.0 microg/mL to 41.4 +/- 23.6
      microg/mL, although serum levels were unchanged. This study demonstrates
      antinociceptive potentiation and delay in the development of morphine tolerance
      by the intrathecal coinfusion of magnesium sulfate and morphine in the rat.
      IMPLICATIONS: The addition of magnesium sulfate, an N-methyl-D-aspartate
      antagonist, to morphine in an intrathecal infusion provided better analgesia than
      morphine alone in normal rats. These results suggest that intrathecal
      administration of magnesium sulfate may be a useful adjunct to spinal morphine
      analgesia.

PMID- 9539612
TI  - Diaphragmatic paralysis complicating alcohol splanchnic nerve block.

PMID- 9539613
TI  - Unsuccessful resuscitation under hypotensive epidural anesthesia during elective
      hip arthroplasty.

PMID- 9539614
TI  - Assessment of the safety and tolerance of 6% hydroxyethyl starch (200/0.5)
      solution: a randomized, controlled epidemiology study.
AB  - None of the natural and synthetic colloids currently available is free from the
      risk of side effects. This study was performed to contribute to the epidemiology
      of adverse reactions of the widely used 200/0.5 hydroxyethyl starch 6% solution
      (HES). Study end points were anaphylactoid reactions during preanesthesia
      infusion and perioperative course, and pruritus 5 days postoperatively (clinical
      examination and inquiry) and 8 wk after application (mailed patient
      questionnaire). We consecutively randomized 750 patients undergoing minor
      elective surgery into two parallel groups treated with HES (from two different
      manufacturers) and one control group treated with lactated Ringer's solution. The
      study population was well matched among the groups and consisted of patients of
      both sexes, aged 18-95 yr, ASA physical status I-III. No drug-related
      anaphylactoid reactions were detected during either of the observation intervals.
      There was no episode of pruritus after the fifth postoperative day. Incidence of
      pruritus after 8 wk was quite frequent but not significantly different (chi2
      test, P = 0.77): 9.1% and 12.0% in the two HES groups and 11.5% in the lactated
      Ringer's solution control group. Except for pruritus, we conclude that HES was
      associated with no more complications than lactated Ringer's solution.
      IMPLICATIONS: Anaphylactoid reactions and pruritus (itching) after the
      administration of a 6% hydroxyethyl starch (200/0.5) versus lactated Ringer's
      solution were assessed in a prospective, randomized, controlled study. There were
      no differences, although there was a more than 10% incidence of pruritus in both
      groups.

PMID- 9539615
TI  - The pharmacokinetics of acetyl starch as a plasma volume expander in patients
      undergoing elective surgery.
AB  - Acetyl starch (ACS) is a new synthetic colloid solution for plasma volume
      expansion and is now undergoing phase 2 clinical trials. We compared the
      pharmacokinetics of ACS with those of hydroxyethyl starch (HES) in 32 patients
      (ASA physical status I and II) undergoing elective surgery. In this randomized,
      double-blind trial, patients received either 15 mL/kg ACS 6% (average molecular
      weight [Mw] 200,000/molar substitution [MS] 0.5) or HES 6% (Mw 200,000/MS 0.5)
      i.v. up to a maximal dose of 1000 mL. Plasma colloid concentrations were measured
      by repetitive arterial blood sampling over 24.5 h. Plasma colloid concentrations
      were detected using a high-pressure liquid chromatography controlled enzymatic
      test. Standard pharmacokinetics were calculated, including initial half-life
      (t(1/2init)), i.e., the time required for a 50% decline of the maximal plasma
      colloid concentration at the end of drug infusion. Whereas HES was eliminated by
      second-order kinetics, ACS followed first-order characteristics. In the first
      hours after i.v. administration, t(1/2init) and clearances were similar in both
      groups. However, the terminal half-life of HES was significantly longer than that
      of ACS (9.29 +/- 1.43 h vs 4.37 +/- 1.06 h). After 16.5 and 24.5 h, ACS showed
      significantly lower plasma concentrations than HES, which indicates that the
      final degradation of ACS by esterases and amylase was significantly more rapid.
      ACS might be an alternative plasma volume expander, which avoids the accumulation
      of persisting macromolecules. IMPLICATIONS: We studied the pharmacokinetics of
      acetyl starch, a newly developed colloid solution for plasma volume substitution,
      compared with hydroxyethyl starch in 32 surgical patients undergoing elective
      major general surgical procedures. In contrast to hydroxyethyl starch, this new
      agent undergoes rapid and nearly complete enzymatic degradation.

PMID- 9539616
TI  - The influence of acute normovolemic hemodilution on the dose-response and time
      course of action of vecuronium.
AB  - To evaluate the influence of acute isovolemic hemodilution on the dose-response
      and time course of action of vecuronium, we studied 60 adult patients with and
      without hemodilution during surgery. The patients with hemodilution underwent
      major elective plastic surgery with an anticipated surgical loss of more than 600
      mL. Anesthesia was induced with thiopental 4-6 mg/kg and fentanyl 2-4 microg/kg
      i.v. and was maintained with 60% nitrous oxide in oxygen. Further increments of
      thiopental 2 mg/kg or fentanyl 2 microg/kg were given as required. Acute
      isovolemic hemodilution in the hemodilution group was induced by drainage of
      venous blood and an i.v. infusion of lactated Ringer's solution and 6% dextran,
      during which hematocrit and hemoglobin decreased from 45.7% to 26.2% and from
      148.5 g/L to 90.2 g/L, respectively. Neuromuscular function was assessed
      mechanomyographically with train-of-four stimulation at the wrist every 12 s, and
      the percent depression of T1 response was used as the study parameter. The dose
      response relationships of vecuronium in the two groups were determined by using
      the cumulative dose-response technique. The results showed that during
      hemodilution, the dose-response curve of vecuronium was shifted to the left in a
      parallel fashion, and the potency of vecuronium was increased. There were
      significant differences in the 50%, 90%, and 95% effective doses between the two
      groups. After the i.v. administration of vecuronium 80 microg/kg, vecuronium
      induced neuromuscular block was significantly longer in the patients with
      hemodilution than in the control patients. The duration of peak effect, clinical
      duration, recovery index, and total duration in the hemodilution patients were
      significantly different from those in the control patients. We conclude that
      hemodilution induces significant changes in the pharmacodynamics of vecuronium.
      IMPLICATIONS: We found that patients with hemodilution were 20% more sensitive to
      vecuronium and had a longer duration of action after the administration of the
      same dose than the controls. This should be taken into account when vecuronium is
      used as a muscle relaxant during acute hemodilution.

PMID- 9539617
TI  - Laryngeal mask airway position and the risk of gastric insufflation.
AB  - A potential risk of the laryngeal mask airway (LMA) is an incomplete mask seal
      causing gastric insufflation or oropharyngeal air leakage. The objective of the
      present study was to assess the incidence of LMA malpositions by fiberoptic
      laryngoscopy, and to determine their influence on gastric insufflation and
      oropharyngeal air leakage. One hundred eight patients were studied after the
      induction of anesthesia, before any surgical manipulations. After clinically
      satisfactory LMA placement, tidal volumes were increased stepwise until air
      entered the stomach, airway pressure exceeded 40 cm H2O, or air leakage from the
      mask seal prevented further increases in tidal volume. LMA position in relation
      to the laryngeal entrance was verified using a flexible bronchoscope. The overall
      incidence of LMA malpositions was 40% (43 of 108). Gastric air insufflation
      occurred in 19% (21 of 108), and in 90% (19 of 21) of these patients, the LMA was
      malpositioned. Oropharyngeal air leakage occurred in 42%, and was independent of
      LMA position. We conclude that clinically unrecognized LMA malposition is a
      significant risk factor for gastric air insufflation. IMPLICATIONS: Routine
      placement of laryngeal mask airways does not require laryngoscopy. In our study,
      fiberoptic verification of mask position revealed suboptimal placement in 40% of
      cases. Such malpositioning considerably increased the risk of gastric air
      insufflation.

PMID- 9539618
TI  - Propofol concentration required for endotracheal intubation with a laryngoscope
      or fiberscope and its interaction with fentanyl.
AB  - The administration of fentanyl with propofol reduces the blood concentration of
      propofol required to achieve adequate anesthesia for tracheal intubation.
      However, different intubation procedures have variable intensities of noxious
      stimulation and may require different levels of anesthesia. The goal of this
      study was to determine the propofol blood concentration at which 50% of patients
      did not respond to stimulation (Cp50) for laryngoscopy, intubation with a
      laryngoscope, insertion of a slotted oral-pharyngeal airway (Ovassapian airway),
      and intubation with a fiberscope when administered in conjunction with fentanyl.
      Patients undergoing elective surgery were given varying amounts of propofol or
      propofol with fentanyl, and their responses to the four procedures listed above
      were assessed. These experiments demonstrated that the propofol concentration
      required for intubation with a laryngoscope was similar to that for intubation
      with a fiberscope, and that the required level was reduced by fentanyl.
      Hemodynamic responses to intubation were lower with a fiberscope than with a
      laryngoscope. We conclude that almost the same concentrations of propofol or
      fentanyl are necessary for suppressing both of the somatic responses to tracheal
      intubation with a fiberscope or a laryngoscope. Hemodynamic responses were
      attenuated more during intubation with a fiberscope. IMPLICATIONS: The propofol
      blood concentrations at which 50% of patients did not respond to stimulation for
      laryngoscopy, tracheal intubation with a laryngoscope, and tracheal intubation
      with a fiberscope were 10.9, 19.6, and 19.9 microg/mL, respectively. These were
      reduced by fentanyl. Hemodynamic responses to intubation were less with a
      fiberscope than with a laryngoscope.

PMID- 9539619
TI  - Interrupted expiratory flow on automatically constructed flow-volume curves may
      determine the presence of intrinsic positive end-expiratory pressure during one
      lung ventilation.
AB  - We studied patients undergoing elective pulmonary surgery to establish whether
      observing interrupted expiratory flow (IEF) on the flow-volume curves constructed
      by the Ultima SV respiratory monitor is a reliable way to identify patients with
      dynamic pulmonary hyperinflation and intrinsic positive end-expiratory pressure
      (PEEPi). Patients' tracheas were intubated with a double-lumen endotracheal tube
      and ventilated with a Siemens 900C constant flow ventilator. In 30 patients,
      PEEPi was determined by the end-expiratory occlusion (EEO) method during the
      periods of two-lung and one-lung ventilation in the lateral position.
      Sensitivity, specificity, positive and negative predictive values, and diagnostic
      accuracy of the IEF method were calculated. From the 122 measurement pairs, PEEPi
      was identified with the EEO method in 65 occasions. The mean level of PEEPi was
      4.4 cm H2O. During one-lung ventilation, the level of PEEPi and the number of
      true-positive findings was significantly higher (PEEPi = 4.7 cm H2O and 32
      episodes) than during two-lung ventilation (2.9 cm H2O and 19 episodes). When the
      level of PEEPi was higher than 5 cm H2O, the predictive value of IEF was 100%.
      The overall sensitivity of the IEF method was 0.78, its specificity was 0.91, and
      its predictive value was 0.92. In conclusion, examination of the flow-volume
      curves displayed on the respiratory monitor may identify patients with dynamic
      hyperinflation and PEEPi during anesthesia for thoracic surgery. IMPLICATIONS: To
      identify patients with intrinsic positive end-expiratory pressure during
      anesthesia without the need to interrupt mechanical ventilation, the flow-volume
      curves of an online respiratory monitor may be examined. The presence of an
      interrupted expiratory flow may suggest the presence of intrinsic positive end
      expiratory pressure with a reasonable accuracy.

PMID- 9539620
TI  - The effects of halothane on single human neuronal L-type calcium channels.
AB  - We investigated halothane's effects on the function of L-type Ca2+ channels in a
      human neuronal cell line, SH-SY5Y, by using the cell-attached patch voltage clamp
      configuration and Ba2+ as the charge carrier. In multiple-channel patches,
      halothane decreased the peak and persistent Ba2+ currents, accelerated the rate
      of inactivation, and slowed the rate of activation. Single-channel analysis
      showed that halothane (0.14-1.26 mM) increased the latency time for the first
      channel opening, increased the lifetime of nonconducting events, increased the
      proportion of short-lived open events, decreased the lifetime of the two open
      populations, and increased the percentage of current traces without channel
      activity. All of the observed halothane effects contribute to the halothane
      induced decrease in macroscopic Ba2+ currents. The halothane concentration
      producing 50% reduction (IC50) of the peak Ba2+ current was 0.80 mM
      (approximately 1.9 hypothetical minimum alveolar anesthetic concentration [H-MAC]
      at 28 degrees C) and of the persistent Ba2+ current was 0.69 mM (approximately
      1.7 H-MAC). The halothane effects did not always occur together, and the Hill
      slope of 1.6 suggested the presence of more than one interaction site or of more
      than one population of L-type Ca2+ channels. Halothane reduces L-type Ca2+
      channel currents in human neuronal cells primarily through the stabilization of
      nonconducting states such as closed (before and after channel opening) and
      inactivated states. IMPLICATIONS: Calcium is a signaling molecule in neurons. We
      measured the effect of halothane on Ba2+ (a Ca2+ surrogate) movement into a human
      neuron-like cell electronically. Ba2+ entry through the L-type channel was
      depressed. Halothane decreased the likelihood of the channel opening and enhanced
      the rate at which the channel closed and inactivated. These actions of halothane
      are probably related to its anesthetic action.

PMID- 9539621
TI  - Successful strategies for improving operating room efficiency at academic
      institutions.
AB  - In this prospective study, we evaluated the etiology of operating room (OR)
      delays in an academic institution, examined the impact of multidisciplinary
      strategies to improve OR efficiency, and established OR timing benchmarks for use
      in future OR efficiency studies. OR times and delay etiologies were collected for
      94 cases during the initial phase of the study. Timing data and delay etiologies
      were analyzed, and 2 wk of multidisciplinary OR efficiency awareness education
      was conducted for the nursing, surgical, and anesthesia staff. After the
      education period, timing data were collected from 1787 cases, and monthly reports
      listing individual case delays and timing data were sent to the Chiefs of
      Service. For the first case of the day, patient in room, anesthesia ready,
      surgical preparation start, and procedure start time were significantly earlier
      (P < 0.01) in the posteducation period compared with the preeducation period, and
      the procedure start time for the first case of the day occurred, on average, 22
      min earlier than all other procedures. For all cases combined, turnover time
      decreased, on average, by 16 min. Unavailability of surgeons, anesthesiologists,
      and residents decreased significantly (P < 0.05) as causes of OR delays.
      Anesthesia induction times were consistently longer for the vascular and
      cardiothoracic services, whereas surgical preparation time was increased for the
      neurosurgical and orthopedic services (P < 0.05). Identification of the etiology
      of OR inefficiency, combined with multidisciplinary awareness training and
      personal accountability, can improve OR efficiency. The time savings realized are
      probably most cost-effective when combined with more flexible OR staffing and
      improved OR scheduling. IMPLICATIONS: We achieved significant improvements in
      operating room efficiency by analyzing operating room data on causes of delays,
      devising strategies for minimizing the most common delays, and subsequently
      measuring delay data. Personal accountability, streamlining of procedures,
      interdisciplinary team work, and accurate data collection were all important
      contributors to improved efficiency.

PMID- 9539622
TI  - The laryngeal mask and high-frequency jet ventilation for resection of high
      tracheal stenosis.

PMID- 9539623
TI  - Eleventh annual meeting of the Society for Pediatric Anesthesia, San Diego,
      California, October 17, 1997.

PMID- 9539624
TI  - Propofol and the supraventricular tachydysrhythmias in children.

PMID- 9539625
TI  - Gastric insufflation and the laryngeal mask.

PMID- 9539626
TI  - Improvement of pulse oximetry signal by EMLA cream.

PMID- 9539627
TI  - Prophylactic use of dantrolene in a patient with central core disease.

PMID- 9539628
TI  - A case of suspected malignant hyperthermia during desflurane administration.

PMID- 9539629
TI  - Comparative doses and cost: esmolol versus labetalol during electroconvulsive
      therapy.

PMID- 9539630
TI  - Prostaglandins in patients with pulmonary hypertension: the route of
      administration.

PMID- 9539631
TI  - Intrathecal fentanyl with small-dose dilute bupivacaine: better anesthesia
      without prolonging recovery.

PMID- 9539632
TI  - Is there a place for meperidine in intravenous regional anesthesia?

PMID- 9539633
TI  - Dose-response function of epidural fentanyl versus sufentanil.

PMID- 9539634
TI  - Latex allergy and anesthesia.

PMID- 9539635
TI  - Collapsed anterior chamber during hypothermic cardiopulmonary bypass.

PMID- 9539637
TI  - Effect of one-month treatment with nonsteroidal antiinflammatory drugs (NSAIDs)
      on gastric pH of rheumatoid arthritis patients.
AB  - The use of NSAIDs is strongly associated with peptic ulceration. The inhibition
      of prostaglandin synthesis with the consequent increase of gastric acidity is
      considered a possible mechanism. Therefore we decided to assess the effect of one
      month treatment with NSAIDs on the circadian gastric pH of rheumatoid arthritis
      (RA) patients. We studied 11 consecutive patients (one man and 10 women, median
      age 55, range 26-72 years) with confirmed RA. None was H. pylori positive. A 24
      hr gastric pH recording was performed both in basal conditions and after one
      month treatment with either indomethacin 150 mg/day (eight cases) or ketoprofen
      300 mg/day (three cases). Only the 10 female patients were eligible for final
      analysis, and six matched healthy subjects not taking NSAIDs were used as control
      group. The number of 24-hr pH readings for various pH thresholds was calculated
      for both populations. The highest acid levels (pH < 3.0) did not differ between
      the two pH profiles of the control group (7440 vs 7391, P = NS), while they
      predominated after the one-month NSAID treatment (10,339 vs 11,440, P < 0.001) in
      RA patients. These findings show that there is an increased gastric acidity after
      one-month of treatment with NSAIDs in female patients with RA of recent onset.
      This may sustain the rationale of using antisecretory agents to prevent
      gastroduodenal ulcerations in these patients.

PMID- 9539638
TI  - One-week triple therapy with lansoprazole, clarithromycin, and metronidazole to
      cure Helicobacter pylori infection in peptic ulcer disease in Korea.
AB  - The efficacy and acceptability of classical bismuth triple therapy may be limited
      by poor patient compliance and adverse effects. It is widely agreed that
      improved, simpler, and reliable therapies are needed to cure Helicobacter pylori
      infection and foster patient compliance. We evaluated the efficacy and side
      effects of a Bazzoli triple therapy substituting lansoprazole for omeprazole for
      H. pylori infection in active peptic ulcer in Korea (30 mg of lansoprazole, 250
      mg of clarithromycin, and 400 mg of metronidazole, all twice daily). H. pylori
      status was evaluated by rapid urease test, histology, and culture at entry and
      four or more weeks after ending antimicrobial therapy. Fifty-eight patients (mean
      age: 43 years) with gastric (N = 30) or duodenal ulcer (N = 28) and H. pylori
      infection were studied. H. pylori was cured in 47 (81%, 95% CI = 69-90%). Mild
      side effects, including vomiting, diarrhea, and itching, were observed in four
      patients (7%). Compliance averaged 95%. Fifty-five ulcers (95%) were healed.
      Pretreatment pylorobulbar deformity was observed in 49 patients (85%), and in 43
      (88%) the deformity disappeared after treatment. Pretreatment metronidazole and
      clarithromycin resistance was observed in 87% and 2% of patients, respectively.
      The cure rate of H. pylori infection was significantly higher in patients >50
      years of age than those <50. Treatment with low-dose one-week lansoprazole,
      clarithromycin, and metronidazole resulted in a relatively low cure rate, but was
      well tolerated. Studies to define the optimal duration, dose, and dosing interval
      of this combination therapy in Korea are needed.

PMID- 9539636
TI  - Improving the gastrointestinal safety of NSAIDs: the development of misoprostol-
      from hypothesis to clinical practice.
AB  - Arthritis is a major source of disability for the American population. It results
      in significant morbidity for the millions of patients affected and costs billions
      of dollars yearly for diagnosis and management. Nonsteroidal antiinflammatory
      drugs (NSAIDs) are the principal therapy for the majority of arthritis patients.
      It has been estimated that more than 15 million people with arthritis take these
      drugs daily. This use is predicted to increase greatly not only as a result of an
      aging population, with the consequent increase in the prevalence of arthritis,
      but also because NSAIDs may prove to have a role in decreasing colonic neoplasia
      and in reducing the likelihood of conditions such as Alzheimer's disease. It is
      therefore increasingly important to understand the nature of the side effects
      associated with these agents as well as ways of decreasing or preventing their
      occurrence. NSAIDs inhibit the enzymes cyclooxygenase-1 and cyclooxygenase-2.
      This reduces the synthesis of prostaglandins and therefore decreases joint
      inflammation, but it may also lead to the development of gastric and duodenal
      ulcers. For this reason, exogenous prostaglandins have been studied for their
      potential role in preventing NSAID-associated ulcers and ulcer complications.
      This paper reviews the development of the prostaglandin E1 analog misoprostol,
      the theory behind its use as a mucosal protective agent, and the results of
      studies in animals as well as in normal volunteers and patients with arthritis.
      Ultimately, a study was performed to evaluate whether misoprostol reduces the
      incidence of serious ulcer complications in patients taking NSAIDs. It is an
      interesting story, which promises to be of increasing importance as NSAID use
      expands to new indications while concern remains about their associated
      complications, especially those related to the gastrointestinal tract.

PMID- 9539639
TI  - Cyclooxygenase inhibition attenuates cholecystokinin-induced gastroprotection.
AB  - Cholecystokinin prevents gastric injury by an unknown mechanism. This study was
      conducted in conscious, fasted female rats in order to assess the role of
      endogenous prostaglandins as a potential protective mechanism for cholecystokinin
      induced gastroprotection. Intravenous administration of cholecystokinin (0.05-5
      nmol/kg) dose-dependently reduced macroscopic injury to the glandular portion of
      the stomach caused by 1 ml of orally administered acidified ethanol (150 mM
      hydrochloric acid-50% ethanol), an effect corroborated by histologic analysis. In
      time course studies, this protective action occurred as early as 10 min following
      cholecystokinin injection (5 nmol/kg intravenously), but was absent at 1 hr.
      Cyclooxygenase inhibition with either indomethacin (5 mg/kg intraperitoneally) or
      aspirin (100 mg/kg intraperitoneally) resulted in a partial reversal in
      cholecystokinin-induced gastroprotection, effects that were similar in magnitude.
      However, while indomethacin reduced gastric mucosal prostaglandin synthesis
      (enzyme-linked immunoassay) by 60%, aspirin almost totally abolished
      prostaglandin synthesis (95% reduction). Cholecystokinin (5 nmol/kg
      intravenously) did not significantly enhance gastric mucosal prostaglandin
      synthesis in the absence of cyclooxygenase inhibition. These data indicate that
      cholecystokinin requires the presence of endogenous prostaglandins in order to
      fully exert its gastroprotective actions. However, release of endogenous
      prostaglandins does not entirely explain the protective response, and additional
      factors likely participate in this action.

PMID- 9539640
TI  - Interleukin-1beta inhibits growth factor-stimulated restoration of wounded rat
      gastric epithelial cell monolayers.
AB  - We examined the effect of interleukin-1beta (IL-1beta) on spontaneous and
      enhanced restoration (cell migration and proliferation) using an in vitro wound
      model comprising a confluent monolayer of rat gastric epithelial RGM1 cells.
      Repair of an artificial wound in a cell monolayer was found to be time- and
      concentration-dependent when the cells were incubated with epidermal growth
      factor (EGF) or transforming growth factor (TGF) -alpha alone for up to 24 hr.
      The growth factors also stimulated DNA synthesis significantly for 24 hr in a
      concentration-related manner. IL-1beta had no effect on wound restoration in the
      absence of the growth factors. However, it markedly inhibited the restoration
      enhanced by EGF and TGF-alpha, the inhibition being about 60% and 70%,
      respectively. In addition, IL-1beta significantly reduced the DNA synthesis
      stimulated by the growth factors. The EGF- and TGF-alpha-enhanced restoration was
      reduced by about 30% by mitomycin C, which potently inhibited the stimulated DNA
      synthesis. Mitomycin C had no effect on the spontaneous restoration. Even when
      treated with mitomycin C, the inhibitory effect of IL-1beta on the enhanced wound
      repair was still observed; however, the extent of the inhibition was decreased.
      These results indicate that IL-1beta inhibits the migration as well as the
      proliferation of gastric epithelial cells enhanced by EGF and TGF-alpha,
      resulting in a failure of wound healing.

PMID- 9539641
TI  - Meal type affects heartburn severity.
AB  - This study compared heartburn severity, number of episodes, and changes in
      esophageal pH induced by three meals. Symptomatic volunteers consumed the
      following on different occasions: McDonald's Quarter Pounder, french fries, and
      chocolate shake; McDonald's Sausage Biscuit with Egg, cheese, raw onion, and
      chocolate milk; and Wendy's Chili and red wine. Increases in reflux episodes over
      baseline for the hamburger, sausage biscuit, and chili meals were 28.8 +/- 5.7,
      36 +/- 5.5 and 43.7 +/- 8.8, respectively. The sausage biscuit and chili
      increased reflux compared to the hamburger (P < 0.05), but the chili did not
      differ statistically from the sausage biscuit meal. Onset and peak heartburn for
      the hamburger, sausage biscuit, and chili meals were 45 and 90, 30 and 120, and
      15 and 150 min, respectively. Despite lower fat content, chili and red wine
      promoted more reflux and heartburn pain than the other meals, demonstrating the
      importance of meal selection in provocative meal studies.

PMID- 9539642
TI  - Proximal gastric motor activity in response to a liquid meal in type I diabetes
      mellitus with autonomic neuropathy.
AB  - Disordered gastric emptying occurs in 30-50% of patients with diabetes mellitus.
      Although the rate of gastric emptying is dependent on the integration of motor
      activity in different regions of the stomach, there is limited information about
      the function of the proximal stomach in diabetes mellitus. In the present study
      the response of the proximal stomach to a liquid meal was examined in eight
      diabetic patients with autonomic neuropathy and gastrointestinal symptoms and in
      10 healthy volunteers, using an intragastric bag connected to an electronic
      barostat. Postprandial relaxation of the proximal stomach was measured as an
      increase of intragastric bag volume at a constant pressure level of 1 mm Hg above
      the intraabdominal pressure. During the experiment the blood glucose levels were
      maintained within the euglycemic range. Before ingestion of the meal the
      intragastric bag volume was larger in the diabetic patients than in the healthy
      volunteers, 234.4 +/- 29.1 ml vs 155.3 +/- 15.3 ml (P = 0.06). The maximum volume
      was not different in diabetics compared to the healthy controls (386.3 +/- 45.2
      ml versus 399.0 +/- 35.2 ml). However, the maximum volume increase was
      significantly less in diabetics (143.7 +/- 38.6 ml) compared to the controls
      (231.4 +/- 30.5 ml, P < 0.04). Bloating was inversely correlated with the volume
      changes, which suggests that impaired relaxation of the proximal stomach may play
      a role in the genesis of this sensation. In conclusion, this study shows a lower
      fasting fundal tone and a decrease in volume change of the gastric fundus after a
      nutrient drink in patients with autonomic neuropathy due to type I diabetes
      mellitus. These abnormalities may play a role in the abnormal distribution of
      food, disordered liquid gastric emptying, and in the genesis of the sensation of
      bloating observed in these patients.

PMID- 9539644
TI  - Role of nitric oxide mechanisms in control of pyloric motility and transpyloric
      flow of liquids in conscious dogs.
AB  - The role of nitric oxide (NO) mechanisms in control of pyloric function and
      transpyloric flow were investigated in six conscious dogs. Antropyloroduodenal
      motility, transpyloric flow, and gastric emptying were measured 15 min after
      intravenous injection of 100 ml of either saline, L-arginine (50 mg/kg), L-NNA (5
      mg/kg), or L-arginine (50 mg/kg) followed by L-NNA (5 mg/kg). Infusion of L-NNA
      was associated with retardation of gastric emptying (65 +/- 6%) in the first 30
      min, in comparison to the saline (90 +/- 3%) or L-arginine (90 +/- 2%). This
      effect was prevented by infusion of L-arginine prior to L-NNA, after which 89 +/-
      3% of the liquid emptied in 30 min. There was a significant reduction (P < 0.05)
      in the number and volume of flow pulses, and an increase in pyloric tone (P <
      0.05) after L-NNA in comparison to the other three test conditions. There were no
      differences, however, in the number of antropyloric or isolated pyloric pressure
      waves under the four conditions. Our findings suggest that NO mechanisms
      influence gastric emptying and transpyloric flow of nonnutrient liquids by
      altering the pyloric tone, thus increasing resistance to flow.

PMID- 9539643
TI  - Ranitidine and nizatidine stimulate antral smooth muscle contractility via
      excitatory cholinergic mechanisms.
AB  - Histamine type 2 receptor antagonists (H2RAs) have been found to alter gastric
      motility. The aims of this study were to determine if H2RAs affect antral
      contractility in vitro and the mechanism of this effect. Guinea pig antral muscle
      strips were pinned in an organ bath after removing the mucosa, and circular
      muscle tension was measured using an isometric force transducer. Gastric myocytes
      were isolated from guinea pig stomach using collagenase digestion, and cell
      lengths were measured using an image analysis system. In muscle strips,
      ranitidine and nizatidine increased the amplitude of spontaneous phasic antral
      contractions in a concentration-dependent fashion with threshold concentrations
      of 5 microM. The order of potency for the H2RAs was ranitidine = nizatidine >>
      cimetidine > famotidine. The contractile effects of ranitidine and nizatidine
      were reduced, but not abolished, by tetrodotoxin and omega-conotoxin GVIA and
      nearly abolished by atropine. In isolated cells, ranitidine and nizatidine, but
      not famotidine or cimetidine, induced concentration-dependent cell shortening,
      with maximal shortening at 10 microM. These contractile effects of ranitidine and
      nizatidine in isolated cells were inhibited by atropine. Ranitidine and
      nizatidine increase antral contractility; this effect appears to be mediated by
      an interaction between ranitidine and nizatidine on cholinergic pathways with
      both direct effects on smooth muscle cholinergic receptors and indirect effects
      by increasing cholinergic neurotransmission.

PMID- 9539645
TI  - Flow cytometric method to detect lymphocyte transformation in drug-allergic
      hepatic injury.
AB  - Flow cytometric methods for the analysis of incorporated bromodeoxyuridine are
      extremely rapid and simple. We investigated whether these methods were useful for
      detecting drug-allergic hepatic injury in 18 patients with drug-allergic hepatic
      injury, 18 healthy controls, and 9 nonallergic patients receiving drugs.
      Peripheral blood mononuclear cells were stimulated with drug solutions.
      Incorporation of bromodeoxyuridine was detected after labeling with FITC, and S
      phase cells were counted by flow cytometry. Percentages of S-phase cells in drug
      stimulated culture minus those in spontaneous cultures were less than 1% in both
      healthy controls and nonallergic patients receiving drugs. Taking 1% as the upper
      limit, 13 patients (72%) were judged as positive. After the in vitro addition of
      interleukin-2, two patients among five who had been judged as negative were
      judged as positive. Lymphocyte transformation test by flow cytometry may be
      useful in the diagnosis of drug-allergic hepatic injury.

PMID- 9539646
TI  - Endoscopic sclerotherapy in porcine esophagus changes luminal cross-sectional
      area and wall distensibility dose- and time-dependently.
AB  - The dose- and time-dependent effects of endoscopic sclerotherapy on luminal cross
      sectional area and wall distensibility were studied in pigs at 5 and 12 cm
      proximal to the gastroesophageal junction by means of impedance planimetry.
      Sixteen healthy animals underwent two sessions of endoscopic sclerotherapy two
      weeks apart with injections of either 5 or 10 ml of 1% Polidocanol in the distal
      7 cm of the esophagus each time. The animals were investigated before
      sclerotherapy, two weeks after each session, and finally six weeks after the last
      session. Six healthy animals were studied as controls. Endoscopic sclerotherapy
      caused luminal narrowing in the sclerosed zone followed by normalization six
      weeks after the last treatment (P < 0.05 in both groups). Wall distensibility
      decreased in the sclerosed zone after treatment with 10 ml sclerosant (P < 0.05)
      followed by partial normalization, while no effect was found after 5 ml
      sclerosant (P > 0.2). Progressive dilations were observed in the proximal
      esophagus in both groups and were most pronounced in the 10 ml group (P < 0.05).
      Wall distensibility did not change proximal to the site of sclerotherapy in
      either group (P > 0.1).

PMID- 9539647
TI  - Dramatic resolution of skin lesions associated with porphyria cutanea tarda after
      interferon-alpha therapy in a case of chronic hepatitis C.

PMID- 9539648
TI  - Suspected biliary complications after laparoscopic and open cholecystectomy
      leading to endoscopic cholangiography: a retrospective comparison.
AB  - To study how suspected postoperative biliary complications are influenced by
      surgical technique, we compared clinical profiles of 63 patients referred for
      ERCP after open (OC) and laparoscopic cholecystectomy (LC) over a four-year
      period. ERCP was not performed for postoperative pain alone and only six (9.5%)
      studies were normal. Referrals after LC were younger (mean 39.1 vs 53.6 years, P
      < 0.001) and ERCP was requested earlier (mean 71.6 vs 2360 days, P < 0.001) in
      the postoperative course. Choledocholithiasis (CDL) alone, the most common
      finding, was successfully managed with a single ERCP in 97.2% of cases. CDL after
      LC occurred in younger patients (35.5 vs 58.9 years, P < 0.01) who presented
      earlier (mean 98.6 days vs 5.1 years, P < 0.01), without biliary ductal
      dilatation (P < 0.01). Although CDL after LC was associated with higher ALT and
      bilirubin levels than after OC, the difference was not statistically significant.
      Cystic duct leaks (LC: six patients, OC: four patients) were typically associated
      with CDL after OC and 90% resolved with endoscopic therapy. Biliary ligation
      (four cases) was managed successfully with choledochojejunostomy. We conclude
      that findings at ERCP for suspected biliary obstruction or injury after OC or LC
      are similar and usually can be endoscopically managed. After LC, referrals
      currently are younger, present much earlier, and retained stones are less likely
      to be associated with ductal dilatation than after OC.

PMID- 9539649
TI  - Biliary, pancreatic, and sphincter of Oddi electrical and mechanical signals
      recorded during ERCP.
AB  - Measurements of biliary tract motility have focused on radiologic and pressure
      measurements to quantify biliary motility rather than measurements of electrical
      activity of the biliary tract. We previously reported the recording of biliary
      electrical signals during ERCP and now report on the continued development and
      validation of a system to measure biliary tract electrical activity as well as
      biliary mechanical activity. In 26 patients presenting with a variety of clinical
      indications, we recorded measurements of electrical activity from the common bile
      duct sphincter (16 patients), pancreatic duct sphincter (eight patients), and/or
      sphincter of Oddi (eight patients). Electrical recordings were performed with a
      specially modified ERCP catheter, using two circular electrodes as well as a
      custom catheter that measured both electrical and mechanical activity. Electrical
      activity of the biliary tract was successfully recorded in 25 of 26 patients
      (96%), including the common bile duct sphincter (16 patients, 62%), pancreatic
      duct sphincter (eight patients, 31%) and sphincter of Oddi (eight patients, 31%).
      Along with the electrical recordings, common bile duct sphincter mechanical
      activity was recorded in 12 patients (67%), pancreatic duct sphincter mechanical
      activity in six patients (33%), and sphincter of Oddi mechanical activity in six
      patients (33%). Frequency analysis of electrical signals revealed a mean
      frequency (cycles/min) of 4.7 +/- 0.5 in the common bile duct sphincter, 4.1 +/-
      0.6 in the pancreatic duct sphincter, and 4.9 +/- 0.7 in the sphincter of Oddi.
      Phasic mechanical frequency in cycles per minute was recorded at a frequency of
      4.8 +/- 0.5 in common bile duct sphincter, 4.0 +/- 0.6 in pancreatic duct
      sphincter, and 5.3 +/- 0.9 in sphincter of Oddi. Tonic pressure (averaged 12.1 +/
      1.5 mm Hg) in common bile duct sphincter, 12.4 +/- 1.4 mm Hg in pancreatic duct
      sphincter, and 15.0 +/- 5.1 mm Hg in sphincter of Oddi. Analysis of wave form
      propagations (noted as percentage antegrade, retrograde, or indeterminant)
      revealed 50% antegrade, 23% retrograde, and 27% indeterminant). One patient was
      recorded on two occasions via ERCP; the same patient had an intraoperative
      recording. All three recordings showed similarities. We conclude that
      measurements of biliary, pancreatic, and sphincter of Oddi electrical and
      mechanical activity are feasible and can be done as part of ERCP. There was good
      correlation between biliary tract electrical and mechanical events and different
      wave form characteristics were noted for different parts of the biliary tree.
      Further studies are warranted to evaluate the potential usefulness of measurement
      of biliary tract electrical activity, and to confirm its correlation with
      mechanical events in the pancreato-biliary tree.

PMID- 9539650
TI  - Nitric oxide mediates cerulein-induced relaxation of canine sphincter of Oddi.
AB  - This study evaluates the hypothesis that cerulein relaxes the sphincter of Oddi
      (SO) via nitric oxide (NO). The spontaneous motility and the response to cerulein
      on the canine SO were recorded using a constant-perfusion technique. N(G)-L
      arginine-methyl-ester (L-NAME) increased the spontaneous motility and dose
      dependently reduced the cerulein-induced inhibitory response of the SO. After
      treatment with L-NAME at higher doses, cerulein induced an excitatory response.
      This effect was reversed by treatment with excess L-arginine. Similar results
      were obtained using cholecystokinin octapeptide in place of cerulein. In separate
      studies, cerulein generated increases in intracellular cAMP and cGMP levels in
      the SO. This indicates that the intracellular mechanism mediating cerulein
      induced relaxation involves the production of cAMP and cGMP. On the other hand,
      treatment with L-NAME absorbed the increase in cAMP and cGMP levels by cerulein.
      These studies demonstrate that cerulein relaxes the canine SO mainly via NO,
      increasing intracellular cAMP and cGMP levels.

PMID- 9539652
TI  - Postprandial cholecystokinin response in patients with chronic pancreatitis in
      treatment with oral substitutive pancreatic enzymes.
AB  - Cholecystokinin (CCK) response to a test meal should be increased in patients
      with pancreatic insufficiency, as trypsin is absent from the duodenum. If
      pancreatic enzymes are added, a restoration of the inhibitory feedback should
      result in lower levels of CCK. Ten patients with chronic pancreatitis and
      steatorrhea were studied. CCK basal and postprandial levels were evaluated the
      day before and 45 and 90 days after treatment with oral pancreatin. Twelve
      healthy volunteers were included as reference group. CCK basal levels did not
      vary. CCK response to a test meal was increased in patients before treatment and
      diminished when oral enzymes were maintained for months even after three days of
      therapy withdrawal. We conclude that long-term therapy with oral enzymes induces
      changes in CCK response that do not regress after three days of treatment
      suspension.

PMID- 9539651
TI  - Similarity in gallstone formation from 900 kcal/day diets containing 16 g vs 30 g
      of daily fat: evidence that fat restriction is not the main culprit of
      cholelithiasis during rapid weight reduction.
AB  - Diets containing essentially no fat, 1-2 g fat per day, have resulted in
      cholesterol gallstones. Greater fat may result in less gallbladder stasis. Do
      gallstones form with greater fat content? We studied 272 moderately obese
      subjects who had normal gallbladder ultrasonograms. The 900 kcal/day liquid diets
      contained either 16 g fat (N = 94) or 30 g fat (N = 178) each day for 13 weeks. A
      second gallbladder ultrasound was performed. Sixteen of 94 (17.0%) of the 16-g
      fat group developed stones with a weight loss of 18 (+/- 7) kg and a body mass
      index (BMI) decrease of 6 (+/- 2) kg/m2. Twenty of 178 (11.2%) of the 30-g fat
      group developed stones (P = 0.18, no difference in stone formation) with similar
      weight loss of 20 (+/- 7) kg (P = 0.08) and BMI decrease of 7 (+/- 2) kg/m2 (P =
      0.04). Substantial fat for rapid weight-reducing diets resulted in gallstone
      formation. Since experiments have shown that our higher fat diet, containing 10 g
      fat per meal, results in maximal gallbladder emptying, cholelithiasis from rapid
      weight loss may not be solely attributable to gallbladder stasis.

PMID- 9539653
TI  - Overexpression of platelet-derived growth factor (PDGF) B chain and type beta
      PDGF receptor in human chronic pancreatitis.
AB  - Platelet-derived growth factors (PDGF) are mitogenic polypeptides that are
      involved in cellular proliferation and tissue repair. The expression of PDGFs and
      type beta PDGF receptor was examined in the normal human pancreas and in chronic
      pancreatitis, a fibrotic disease associated with fibroblastic proliferation,
      atrophy, and acinar cell dedifferentiation. In the normal human pancreas, PDGF A
      chain mRNA levels were relatively abundant, whereas PDGF B chain mRNA levels were
      not detected, and type beta PDGF receptor mRNA transcripts were present at low
      levels. In the normal pancreas, PDGF immunoreactivity was present in islet cells,
      whereas type beta PDGF receptor immunoreactivity was present in acinar cells. In
      chronic pancreatitis, PDGF A chain mRNA transcripts were also abundant, and 11 of
      19 samples exhibited the PDGF B chain mRNA transcript. In addition, there was a
      significant increase in the mRNA levels of type beta PDGF receptor in the
      pancreatitis samples by comparison with the normal pancreas (P < 0.001). In
      chronic pancreatitis tissues, PDGF and type beta PDGF receptor immunoreactivity
      were present in acinar, ductal, islet, and endothelial cells, fibroblasts, and
      leukocytes. The concomitant overexpression of PDGFs and of the type beta PDGF
      receptor points to the existence of autocrine and paracrine PDGF-dependent loops
      in human chronic pancreatitis.

PMID- 9539654
TI  - Somatostatin attenuates microcirculatory impairment in acute sodium taurocholate
      induced pancreatitis.
AB  - Using in vivo microscopy, red blood cell (RBC) velocities, functional capillary
      density (FCD), and overall changes in capillary blood flow (PI) were estimated
      following intraductal infusion of sodium taurocholate (0.8 ml; 4%) alone or in
      combination with systemic administration of somstostatin (single bolus SMS 100
      microg/100 g body wt). Sodium taurocholate mediated a significant transient
      decrease in RBC velocities and a sustained decrease in FCD, which were paralleled
      by dramatic flow heterogeneity. Therefore, a significant reduction in overall
      capillary blood flow was calculated. Additional SMS treatment reduced
      microcirculatory impairment as expressed by reduction of blood flow
      heterogeneity, a less rarified functional capillary density, and a recovery of
      RBC velocities and acinar capillary overall perfusion to control values. As a
      result of this microcirculatory improvement, pancreas histology revealed slightly
      less severe tissue damage compared to the non-SMS-treated pancreatitis group.
      These findings demonstrate that exogenous SMS infusion can improve
      microcirculatory failure in acute biliary pancreatitis, which should have a
      beneficial effect on the course of the disease.

PMID- 9539655
TI  - Acute mesenteric ischemia following intranasal cocaine use.

PMID- 9539656
TI  - Fecal lysozyme in assessment of disease activity in inflammatory bowel disease.
AB  - This study was undertaken to determine whether measurement of fecal lysozyme is
      helpful in determining disease activity in inflammatory bowel disease. In 112
      patients with Crohn's disease, 46 patients with ulcerative colitis, and 40
      controls, fecal lysozyme concentration was measured. Results were correlated with
      CDAI and AI in Crohn's disease and with Truelove and Witts' grading in ulcerative
      colitis. Fecal lysozyme concentration (mean +/- SEM) was significantly (P <
      0.001) higher in Crohn's disease (75 +/- 14 microg/g) and ulcerative colitis (238
      +/- 33 microg/g) than in controls (6 +/- 1 microg/g). There was only a weak
      correlation between fecal lysozyme concentration and CDAI (r = 0.32; P = 0.001)
      and AI (r = 0.38; P < 0.0005) in patients with Crohn's disease and with Truelove
      and Witts' grading (r = 0.47; P = 0.001) in ulcerative colitis. When CDAI > or =
      150 or AI > or = 100 were used as the standard for active disease, fecal lysozyme
      concentration was elevated in 78% of patients with active colonic Crohn's
      disease. In ulcerative colitis fecal lysozyme concentration was increased in
      active disease (95% in grade II and 94% in grade III) as compared 33% in grade I.
      Measurement of fecal lysozyme is of little help in diagnosing and determining
      disease activity of inflammatory bowel disease as whole, but it may be of help
      for diagnosis and assessment of activity of colonic IBD.

PMID- 9539657
TI  - Expression of E-selectin, sialyl Lewis X, and macrophage inflammatory protein
      1alpha by colonic epithelial cells in ulcerative colitis.
AB  - The pathogenic significance of cell adhesion molecules (CAMs) in ulcerative
      colitis (UC) is largely unknown. Colonic expression of E-selectin, sialyl Lewis X
      (sLe(x)), and macrophage inflammatory protein-1x (MIP-1alpha) as well as serum
      concentrations of E-selectin and MIP-1alpha in UC were studied. Thirty patients
      with UC, 10 patients with irritable bowel syndrome, and 10 healthy subjects were
      included. Colonic biopsies were stained immunohistochemically, and blood
      concentrations were measured with an ELISA technique. Soluble E-selectin did not
      correlate with diagnosis or disease activity. MIP-1alpha was below the detection
      limit. Epithelial cells expressed all three molecules, both on surface membranes
      and intracellularly. sLe(x) staining was weaker (P = 0.0002) and MIP-1alpha
      staining stronger (P = 0.014) in UC patients than in controls. Leukocyte MIP
      alpha staining correlated with diagnosis (P = 0.021), sLe(x) staining (P =
      0.023), and colonoscopy (P = 0.018). It is shown that E-selectin, sLe(x), and MIP
      1alpha are synthesized and expressed by epithelial cells, indicating that CAMs
      are not only involved in leukocyte extravasation and migration, but also in the
      interaction between leukocytes and colonic epithelium. This knowledge might
      contribute to the development of improved treatments in UC.

PMID- 9539658
TI  - Ketotifen therapy for acute ulcerative colitis in children: a pilot study.
AB  - Eosinophils contribute to the inflammatory process in a variety of chronic
      inflammatory bowel diseases. Ketotifen is beneficial in experimental models of
      colitis and in patients with eosinophilic gastroenteritis. Therefore, we
      investigated the efficacy of ketotifen therapy for the treatment of active
      ulcerative colitis. Children with newly or previously diagnosed ulcerative
      colitis with mild-moderate disease activity were treated with ketotifen at a
      dosage of 4 mg daily for eight weeks. Efficacy was determined by a physician
      disease severity index and by endoscopic and histologic examinations. Ten
      patients were enrolled. Symptoms improved in four patients and resolved
      completely in one patient. There was endoscopic improvement in three patients and
      histologic improvement in one. Increased eosinophils on rectal biopsy at entry
      were present in two of the responders. Five patients withdrew due to a lack of
      symptomatic improvement. No adverse events were identified. Low-dose ketotifen
      offers a limited therapeutic advantage in active ulcerative colitis that may be
      enhanced in the subgroup of patients with a high eosinophil count in the colonic
      mucosa. Further study of therapeutic efficacy with increased dosages of the mast
      cell stabilizer for acute and maintenance therapy is warranted.

PMID- 9539659
TI  - Human defunctionalized colon: a histopathological and pharmacological study of
      muscularis propria in resection specimens.
AB  - Despite the regression of "diversion colitis," temporary functional disorders
      after bowel continuity restoration could be caused by changes in the smooth
      muscle of excluded segments; however, studies on the muscularis propria have
      yielded contradictory results. This study was aimed at evaluating possible
      histopathological changes in muscular layers and motility of the defunctionalized
      human colon. Ten patients with defunctionalized colorectum (group A) and 10
      controls (group B) underwent restorative or primary resection surgery. Strips
      were taken proximal to the colostomy (specimens A1) and the defunctionalized
      segment (specimens A2), and from the proximal (specimens B1) and distal extremity
      (specimens B2) of resected colons. Measurements of the thickness of the
      muscularis propria and of the volume density of the myenteric plexus, as well as
      of spontaneous motility and responses to electrical and pharmacological
      stimulation were taken. The muscularis propria was thicker in A2 than in A1
      specimens (P = 0.004) and in B2 than in B1 specimens (P = 0.007). No differences
      were recorded either in the myenteric plexus volume density or in colonic
      motility. No differences were recorded in intergroup comparisons. As no
      structural or functional changes related to defunctionalization were found,
      clinical disorders after colorectal restoration could rather result from
      underlying colonic pathology and/or incomplete distal colon resection.

PMID- 9539660
TI  - Qualitative changes in enteric flora and short-chain fatty acids after intestinal
      resection.
AB  - Our aim was to determine the effect of intestinal transection and resection on
      the prevalence of enteric flora and evaluate whether any such changes alter
      luminal SCFA and lactic acid content. Dogs underwent either 50% proximal (PR, N =
      6) or distal (DR, N = 7) resection, distal resection with bypass of the ileocecal
      junction (DRBP, N = 9) or midpoint transection alone performed to serve as the
      appropriate control for luminal sampling for either proximal (PTC, N = 6) or
      distal (DTC, N = 7) resection. Studies were performed every four weeks for 12
      weeks. Both jejunum and ileum had >10(5)/ml aerobic bacteria, most commonly E.
      coli. Streptococcal species were more common in the normal jejunum than ileum but
      were found in the ileal remnant after PR. Significant (>10(5)) anaerobic growth
      occurred infrequently in the jejunum, and DR did not increase anaerobic growth in
      jejunum unless DRBP was performed (93% vs 62% DR, 45% DTC, 20% normal jejunum, P
      < 0.05). Clostridium species increased significantly in the jejunal remnant after
      DRBP. Significant anaerobic growth occurred infrequently in normal ileum but
      increased after PR (89% vs 50% PTC, P < 0.05). Flora normally found in the
      jejunum tended to increase in the ileum after PR. Jejunal SCFA increased after
      DRBP (3126 +/- 577 microg/ml vs 1600 +/- 301 DTC, P < 0.05) but not DR (1791 +/-
      321 microg/ml). Significant (>10(5)) anaerobic bacterial growth was associated
      with increased SCFA content (2717 +/- 381 vs 1029 +/- 170 microg/ml, P < 0.05)
      and the presence of lactic acid (30% vs 5%, P < 0.05), but there was no
      correlation between the presence of specific bacteria and SCFA and lactic acid.
      Following resection of the proximal small intestine, the intestinal remnant tends
      to assume the bacteriologic characteristics of the resected segment. Following a
      distal resection, the presence of an intact ICJ protects against the
      proliferation of a flora characteristic of the distal intestine; resection with
      bypass of the ICJ results in the appearance of coliforms in the jejunal remnant.
      These changes in enteric flora do not correlate with content of specific SCFA and
      lactic acid in the small intestine.

PMID- 9539662
TI  - Absorption-enhancing effects of sodium caprate and palmitoyl carnitine in rat and
      human colons.
AB  - We examined the enhancing action of sodium caprate and palmitoylcarnitine on the
      permeability of fluorescein isothiocyanate dextran 4000 as a paracellular
      permeant compound in isolated rat and human colon samples using the Ussing-type
      chamber method. In the absence of an enhancer, the permeation clearance of
      fluorescein isothiocyanate dextran 4000 was not significantly different in the
      rat and human colons, but the electric membrane resistance was smaller in the rat
      colon than in the human colon. Sodium caprate and palmitoylcarnitine increased
      permeation clearance and decreased electric membrane resistance in both types of
      colonic membrane, showing that the rat colon can be used as a model of the human
      colon for studies of enhancer effects. A calmodulin antagonist significantly
      inhibited the action of sodium caprate in both colonic membranes. However, it
      tended to promote the effects of palmitoylcarnitine on permeation clearance and
      electric membrane resistance. These results suggest that sodium caprate induces
      the contraction of the perijunctional actomyosin ring to widen the tight junction
      and that the mechanism of palmitoylcarnitine is different from that of sodium
      caprate in the human colon, as reported previously for Caco-2 cell monolayers.

PMID- 9539661
TI  - Pentobarbital affects transepithelial electrophysiological parameters regulated
      by protein kinase C in rat distal colon.
AB  - For rat distal colon, the transepithelial electrical parameters, short circuit
      current (Iscc) and transepithelial electrical resistance (TER), respectively,
      measure net transepithelial electrolyte transport activity and the barrier
      function of the epithelium. Studies with a variety of epithelial cell cultures
      have shown greater than 90% decreases of TER within minutes of exposure of in
      vitro cell sheets to phorbol esters. The phorbol ester and protein kinase C (PKC)
      activator, phorbol dibutyrate (PDBU), was observed to produce an over 100%
      elevation of Iscc but only a small yet significant 20-30% decrease of TER across
      rat distal colon. Inhibition of the above effects of PDBU by the PKC inhibitor
      bisindolylmaleimide (GFX) is further evidence that in rat distal colon, Iscc and
      TER are under regulatory control by PKC. When animals received anesthesia with
      intraperitoneal pentobarbital prior to removal of the colon, the effect of PDBU
      on Iscc was significantly reduced, and the effect of PDBU on TER was almost
      completely inhibited. This effect of pentobarbital on PKC-mediated
      transepithelial permeability parameters is consistent with the known ability of
      anesthetics to alter protein kinase C activity. Exposure of rat colon to
      pentobarbital produced as much as a 90% inhibition of calcium-dependent PKC
      activity, whereas calcium-independent activity was stimulated by as much as 35%.
      Prior anesthetic use may be therefore a complicating factor in observing PKC
      mediated effects on epithelial barrier function using epithelial tissue models.

PMID- 9539663
TI  - Impairment of intestinal mucosal antioxidant defense system during Salmonella
      typhimurium infection.
AB  - The mucosal pathology of Salmonella typhimurium infection may in part be due to
      the excessive production of reactive oxygen species (ROS). The influence of S.
      typhimurium infection on the intestinal mucosal antioxidant defense system was
      investigated. We injected ligated rat ileal loops with Salmonella live culture or
      toxin. After 18 hr of infection, the animals were killed and enterocytes isolated
      from the ileal loops. The enterocyte-reduced glutathione (GSH) content and
      activities of the enzymes superoxide dismutase (SOD), glutathione peroxidase (GSH
      Px), catalase, glutathione-S-transferase (GST), glutathione reductase (GR), and
      glucose-6-phosphate dehydrogenase (G6PDH) were spectrophotometrically estimated.
      The vitamin E and A contents were determined by high-performance liquid
      chromatography (HPLC). In both the Salmonella live culture and toxin-treated
      groups, the enterocyte GSH and vitamin E contents and activities of the enzymes
      SOD, GSH-Px, catalase, GR, and G6PDH were significantly decreased as compared to
      the control group. However there was a significant increase in the enterocyte
      activity of GST. There was no change in the vitamin A content of the enterocytes.
      These findings might indicate a decreased endogenous intestinal protection
      against ROS in S. typhimurium-mediated infection, which could contribute to the
      pathogenesis of the disease.

PMID- 9539664
TI  - In vivo alterations of fluid and electrolyte fluxes in rat colon by gamma
      irradiation.
AB  - Colonic function in rats was investigated up to 14 days following exposure to
      whole-body gamma irradiation (8 Gy) using a combination of in vivo and in vitro
      approaches. Water and electrolyte fluxes were measured in vivo under anesthesia
      by insertion of an agarose cylinder into the descending colon. Short-circuit
      current responses (Isc; basal, agonist-stimulated) of distal colon were measured
      in vitro as were mannitol and sodium fluxes. Water and electrolyte absorption
      (Na, Cl) was markedly reduced at four days after irradiation but returned to
      normal at seven days. Potassium secretion was increased from one to seven days
      after exposure. There were no differences in basal Isc, Na, or mannitol fluxes at
      four days but responses to secretagogues (5-hydroxytryptamine, forskolin,
      carbachol) were attenuated. No morphological alterations were associated with
      these functional modifications.

PMID- 9539665
TI  - Intra- and extracellular water dynamics on rehydration in cholera and noncholera
      patients.
AB  - To estimate the intra- and extracellular body water compartments during
      rehydration of patients with cholera and noncholera diarrhea by bioimpedance
      analyzer, we studied 30 patients with acute watery diarrhea. Total body water
      (TBW), intracellular water (ICW), and extracellular water (ECW) of severely
      dehydrated adult patients were measured with a dual frequency bioimpedance
      analyzer at different phases of rehydration. Fluid compartments between cholera
      and noncholera patients were compared. Cholera patients gained more TBW than
      noncholera patients during recovery. Unlike patients with noncholera diarrhea,
      the gain in cholera patients was mainly contributed by the ICW (1.5 +/- 1.6 vs
      3.0 +/- 1.2 liters, respectively, P < 0.01). It was also observed that the
      recovery of the ICW compartment in cholera patients occurred rapidly within the
      first 2 hr after infusion. Differential dynamics of body water compartments in
      cholera compared to noncholera patients as observed in this study may contribute
      further to understanding the mechanism of dehydration in diarrheal disease, which
      might help in improving case management.

PMID- 9539666
TI  - Plasma cholecystokinin and gallbladder responses to increasing doses of bombesin
      in celiac disease.
AB  - Impaired postprandial gallbladder emptying in celiac disease has been attributed
      to an absence of appropriate cholecystokinin release. To determine if a flat
      jejunal mucosa in celiac patients is related to a reduced cholecystokinin
      secreting capacity, increasing doses of bombesin were infused into six patients
      with celiac disease and a flat jejunal mucosa (group A), in seven celiac patients
      with a normal jejunal mucosa while on a gluten-free diet (group B), and in seven
      healthy controls (group C). Bombesin induced significant (P < 0.05) increments of
      plasma CCK to a maximum value of 1.0 +/- 0.3 pM in group A, to 1.5 +/- 0.3 pM in
      group B, and to 1.2 +/- 0.3 pM in group C (NS between groups), that were
      accompanied by significant (P < 0.05) gallbladder emptying responses of 70 +/- 4%
      in group A, 47 +/- 10% in group B and 65 +/- 5% in group C. Dose-response
      relationships were not different between groups. We conclude that there is no
      major impairment of gallbladder responsiveness to bombesin or of cholecystokinin
      secreting capacity in patients with a flat jejunal mucosa due to celiac disease.

PMID- 9539667
TI  - Sideropenic anemia and celiac disease: one study, two points of view.
AB  - Recent studies have pointed to the relationship between iron deficiency anemia
      and celiac disease, although data on the prevalence of celiac disease in anemic
      patients have been conflicting, and there is no agreement on the best screening
      procedure for CD in these patients. Our aims were to evaluate the relationship
      between anemia and celiac disease (CD) from two different points of view--the
      hematology clinic and the pediatric gastroenterology department--and to evaluate
      the utility of anti-endomysial antibody determination in screening anemic
      patients for CD using human umbilical cord as substrate. We studied 130 patients
      with CD (58 males, 72 females; median age 18 months) diagnosed at a department of
      Pediatric Gastroenterology, and 85 patients with iron deficiency anemia (38
      males, 47 females; median age 48 years) observed at a hematology outpatient
      clinic. From the 85 adult patients with iron deficiency anemia, we selected a
      subgroup of 25 subjects with no improvement in Hb after two months of iron
      therapy (80 mg/day orally). Routine hematochemical tests were performed in all
      215 patients. All pediatric and adult subjects underwent immunological screening
      for celiac disease (AGA and EmA assay); intestinal biopsy was also performed on
      patients testing positive. In the adult anemic patients a serum sample was stored
      at -20 degrees C on first observation, and after 6-18 months EmA on human
      umbilical cord were assayed. In the pediatric patients with CD, anemia was
      observed in 91/130 patients (70% of cases, the most frequent symptom after poor
      growth); however, this was the only presenting symptom of CD in 2/130 patients
      (1.5% of cases). Anemia was sideropenic in 41/91 patients (iron <45 microg/dl,
      ferritin <15 microg/liter). In the adult patients with iron deficiency anemia,
      immunological screening (AGA and EmA) showed suspected CD in 5/85 cases (5.8%),
      with diagnosis confirmed on intestinal biopsy. These five patients were in the
      subgroup of iron supplementation therapy nonresponders. CD prevalence in the
      refractory anemia subgroup was, therefore, 5/25 (20%). On diagnosis the
      hematological indices of the anemia + CD patients were not different than those
      of the refractory anemia patients without CD. The median age of the CD + anemia
      patients was significantly lower than that of the whole group of anemic subjects,
      and there was also a prevalence of females (4/5 cases). The results of the EmA
      determination on human umbilical cord in the adult anemic patients showed a
      perfect concordance with those using a traditional kit that uses monkey esophagus
      as substrate. In the pediatric age group many cases of CD with anemia as the only
      sign of the disease are probably not diagnosed. In our adult patients with
      sideropenic anemia, CD prevalence was 5-6%; however, the observation of anemic
      patients not responding to oral iron therapy makes a diagnosis of CD much more
      probable. EmA determination on human umbilical cord is the most logical approach
      to screen anemic patients for suspected CD.

PMID- 9539668
TI  - Small intestine bacterial overgrowth presenting as protein-losing enteropathy.

PMID- 9539669
TI  - Understanding and measurement of muscle tone as related to clinical muscle pain.
AB  - Measurable sources of muscle tension include viscoelastic tone, physiological
      contracture (neither of which involve motor unit action potentials), voluntary
      contraction, and muscle spasm (which we define as involuntary muscle
      contraction). The latter two depend on motor unit action potentials to generate
      the tension. Total muscle tension is most accurately measured as stiffness.
      Thixotropy of muscle is an ubiquitous and functionally important phenomenon that
      is not commonly recognized. A clinical pain condition associated with increased
      muscle tension is tension-type headache, which is largely muscular in origin; it
      is often caused by myofascial trigger points, but not by a pain-spasm-pain cycle,
      which is a physiologically and clinically untenable concept. Clinical conditions
      associated with painful muscle spasm include spasmodic torticollis, trismus,
      unnecessary muscle tension, nocturnal leg cramps, and stiff-man syndrome.

PMID- 9539670
TI  - Sympathetic nerve activity after acupuncture in humans.
AB  - The aim of the present study was to determine if acupuncture stimulation inhibits
      sympathetic nerve activity in humans. Multiunit efferent postganglionic
      sympathetic activity was recorded with a tungsten microelectrode inserted in a
      muscle fascicle of the peroneal nerve. Mean arterial pressure, heart rate and
      skin blood flow were also monitored. Pain thresholds were measured by electrical
      tooth pain stimulation. After a 30 min rest, acupuncture needles were inserted
      bilaterally into the Li 11 and the Li 4 acupuncture points, and manipulated until
      'chi' cramp-like sensation was reported. Electrical stimulation (2 Hz, 0.6-0.8 ms
      duration, maximal tolerated stimulation without discomfort) was delivered for 30
      min and the physiological recordings were continued for 90 min after the end of
      acupuncture. In a placebo control experiment, the same procedure was followed,
      except that acupuncture needles were inserted subcutaneously and no manipulation
      or stimulation was given. The stimulator delivered pulses to an unconnected
      channel, hence, the same audiovisual stimuli were experienced as with
      acupuncture, and care was taken to ask the same questions about sensations in the
      placebo and the acupuncture groups. Electroacupuncture produced an increase in
      pain threshold which was paralleled by a transient increase in muscle sympathetic
      nerve activity. During acupuncture, there was a small increase in heart rate and
      mean arterial pressure, but there was no post-acupuncture hypotension. The
      placebo control procedure did not change pain threshold or sympathetic nerve
      traffic. The findings suggest that electroacupuncture produces moderate
      hypoalgesia in humans paralleled by a significant increase in muscle sympathetic
      nerve activity.

PMID- 9539671
TI  - Fos protein induction in the medullary dorsal horn and first segment of the
      spinal cord by tooth-pulp stimulation in cats.
AB  - Electrophysiological studies using the single neuron recording technique have led
      to the hypothesis that nociceptive neurons in the medullary dorsal horn (MDH) and
      the first segment of the spinal cord (C1) encode the stimulus intensity of
      noxious stimuli applied to the tooth pulp. The present study utilized the Fos
      protein technique in combination with electrical and chemical stimulation of the
      tooth pulp to test this hypothesis. Upper canine tooth-pulp stimulation with
      intensities just above the threshold stimulus intensity for evoking the jaw
      opening reflex (JOR) did not produce a clear expression of Fos protein-like
      immunoreactive (LI) cells in the MDH and C1 of cats. Fos protein-LI cells were
      mainly found in the superficial laminae (laminae I-II) of the MDH and C1 after
      tooth-pulp stimulation of 200% of the JOR threshold intensity. When higher
      intensities (400-600% of the JOR threshold intensity) or mustard oil were
      applied, Fos protein-LI cells were also found in laminae III-IV as well as in
      laminae I-II. The number of Fos protein-LI cells significantly increased when
      600% of the JOR threshold intensity or mustard oil was applied. Furthermore, the
      rostro-caudal distribution of Fos protein-LI cells was greater following
      increases in stimulus intensities and the greatest after mustard oil application.
      These data suggest that the change in number and spatial arrangement of
      nociceptive neurons in the MDH and C1 reflect changes in the encoding of the
      stimulus intensity applied to the tooth pulp.

PMID- 9539672
TI  - Pain progression, intensity and outcomes following tonsillectomy.
AB  - The objective of this study was to assess outcomes of pediatric day surgery
      tonsillectomy. A total of 129 children, aged 5-16 years, and their parents were
      recruited from three urban hospitals which provided pediatric day surgery.
      Children reported pain on a visual analogue scale (VAS) in day surgery and then
      daily at home for 7 days. Parents reported outcomes of surgery, including fluid
      intake, nausea, vomiting and sleep disturbances. They also recorded analgesic
      administration. Three main results related to extent and duration of pain,
      quality of management of pain, and effect of pain on utilization of health
      services. Tonsillectomy caused considerable pain which lasted more than 7 days.
      Pain followed a trajectory of intense or moderately intense pain for the first 3
      days followed by a gradual decline over the next 4 days. In general, post
      tonsillectomy pain was poorly managed by health professionals and parents. An
      unexpected observation was that children who had a bupivacaine infiltration of
      the tonsil fossa during surgery had significantly more pain in the evening of
      surgery than children who did not have an infiltration. The increase in
      postoperative pain experienced by those who had the infiltration was attributed
      to quality of pain management. Children with persistent pain (those who did not
      follow the typical trajectory) were likely to be taken to a medical practitioner.
      One-third of the sample made unscheduled visits to practitioners with most
      occurring from Day 4 to Day 7 of the follow-up.

PMID- 9539673
TI  - Cold-induced pain and prickle in the glabrous and hairy skin.
AB  - Little is known concerning the mechanisms underlying the perception of cold pain
      in humans. An appreciation of these mechanisms is important to understand and
      possibly treat those disorders in which cold stimuli evoke unpleasant sensations.
      To study cold pain, I have conducted psychophysical experiments on 16 healthy
      subjects. A peltier-type stimulator (20 x 25 mm) was used to deliver stimuli to
      sites on the thenar eminence (glabrous skin) and volar forearm (hairy skin) of
      each arm. Each trial consisted of a 90 s, 2 degrees C stimulus that was preceded
      and followed by a 35 degrees C stimulus. A computer-based visual analog scale was
      used to collect continuous pain ratings throughout each trial. In experiment 1,
      nine subjects rated the overall evoked pain intensity (four trials/skin type) and
      the prickle component (four trials/skin type). Typically, subjects perceived the
      cold-evoked pain as prickly, cold/freezing and achy. The pain intensity and
      quality was similar for glabrous and hairy skin sites within individual subjects.
      Pain intensity gradually rose to a plateau by approximately 60 s into each trial.
      The prickle component differed amongst subjects due to its variable time course.
      Subjects consistently reported an intense, brief jab of prickle at both hairy and
      glabrous sites during the rewarming phase. In experiment 2, nine subjects rated
      the pain intensity during the cold stimulus before and during a compression
      ischemic block of Abeta/Adelta fiber conduction. The dominant sensation evoked by
      the cold stimulus in the hairy and glabrous skin during the block was a sharp,
      hot/burning pain. The block did not consistently affect the total pain at the
      hairy sites. However, most subjects reported more pain during the block at the
      glabrous sites. These data suggest that noxious cold stimuli affect a mosaic of
      primary afferent input and central processing resulting in a complex pain
      experience which may differ in glabrous and hairy skin.

PMID- 9539674
TI  - Vibrotactile amplitude and frequency discrimination in temporomandibular
      disorders.
AB  - The purpose of this study was to determine whether the elevation in vibrotactile
      detection threshold, found in many individuals with temporomandibular disorders
      (TMD), is paralleled by suprathreshold impairments. Participants with TMD were
      compared with pain-free control subjects in their ability to discriminate on the
      basis of differences in amplitude and frequency between vibratory stimuli
      delivered to the face. The TMD group was significantly impaired with respect to
      frequency discrimination, but not amplitude discrimination. This dissociation
      suggests that the cortical processing of vibrotactile signals may be affected in
      TMD patients. TMD participants' estimates of the intensity of their spontaneous
      and palpation-evoked pain did not significantly correlate with performance on
      either discrimination task; this finding makes it unlikely that impaired
      vibrotaction in TMD is primarily the result of a pain-dependent gating of tactile
      signals.

PMID- 9539675
TI  - Attenuation of IGF-1 antinociceptive action and a reduction in spinal cord gene
      expression of its receptor in experimental diabetes.
AB  - Insulin-like growth factor I (IGF-1) is trophic to sensory, motor and sympathetic
      neurons. Intrathecal (i.t.) administration of IGF-1 produced analgesic effects
      when tail flick/withdrawal latency was used as an indicator. This action was
      blocked by genistein (an inhibitor of tyrosine kinase) but not by atipamezol (an
      alpha2 adrenoreceptor antagonist), naloxone (an opioid antagonist) or
      glibenclamide (a blocker of ATP sensitive K+ channels). Induction of diabetes
      with streptozotocin (STZ, 55 mg/kg, i.v.) impaired the ability of IGF-1 to
      elevate nociceptive threshold. This phenomenon was not seen in normal animals
      rendered hyperglycemic with D-glucose (20 mmol in 2.5 ml of saline, i.p.). PCR
      based assay revealed that the lumbar region of the spinal cord expresses mRNA
      transcripts for IGF-1 and its receptor. The rates of expression of both of these
      transcripts were reduced during diabetes. The above behavioral and biochemical
      abnormalities induced by the diabetic state were partially restored following
      replacement therapy with insulin. Overall, our data suggest that a receptor
      linked tyrosine kinase mediates the antinociceptive effect of IGF-1.
      Additionally, the attenuation in the ability of IGF-1 to elevate nociceptive
      threshold may be a consequence of reduced gene expression of IGF-1 receptor
      within the spinal cord.

PMID- 9539676
TI  - Daily diary and ambulatory activity monitoring of sleep in patients with insomnia
      associated with chronic musculoskeletal pain.
AB  - Insomnia is a significant problem for many people with chronic pain. In this
      study, we used a combination of daily sleep diaries and ambulatory activity
      monitoring (actigraphy) to: (i) examine the nature and severity of the sleep
      disturbance in this patient group; (ii) determine the concordance between sleep
      diary and actigraph measures of different sleep parameters; (iii) assess the
      reliability of sleep parameters across nights; and (iv) identify the clinical
      correlates of insomnia severity. Forty subjects with insomnia associated with
      chronic musculoskeletal pain completed questionnaires addressing clinical issues
      of pain severity, medication use, sleep quality, and affective distress. For 2
      consecutive nights, each subject then completed a sleep diary and wore an
      actigraph unit on the non-dominant wrist. The results showed that the sleep
      diaries and the actigraphs provided similar estimates of total sleep time, time
      awake after sleep onset, and sleep efficiency, but differed in the measurement of
      sleep onset latency and nocturnal awakenings. Both methods of assessment
      exhibited low to moderate reliability across nights. Measures of the same sleep
      parameters across the two methods of assessment showed low concordance. Of the
      clinical variables, pain severity had the strongest association with disturbed
      sleep, but only using the diary method of assessment. Subjects who reported high
      pain severity also reported greater sleep impairment than subjects with low pain
      severity, but this was not confirmed by actigraphy. In general, both methods of
      assessment point to the significance of insomnia associated with chronic
      musculoskeletal pain as a distinct clinical problem, but the activity monitoring
      and self-report procedures provide different information. These findings suggest
      that multi-method assessment is an important consideration for studies of
      insomnia in patients with chronic pain.

PMID- 9539677
TI  - Different strategies of modulation can be operative during hypnotic analgesia: a
      neurophysiological study.
AB  - Nociceptive electrical stimuli were applied to the sural nerve during
      hypnotically-suggested analgesia in the left lower limb of 18 highly susceptible
      subjects. During this procedure, the verbally reported pain threshold, the
      nociceptive flexion (RIII) reflex and late somatosensory evoked potentials were
      investigated in parallel with autonomic responses and the spontaneous
      electroencephalogram (EEG). The hypnotic suggestion of analgesia induced a
      significant increase in pain threshold in all the selected subjects. All the
      subjects showed large changes (i.e., by 20% or more) in the amplitudes of their
      RIII reflexes during hypnotic analgesia by comparison with control conditions.
      Although the extent of the increase in pain threshold was similar in all the
      subjects, two distinct patterns of modulation of the RIII reflex were observed
      during the hypnotic analgesia: in 11 subjects (subgroup 1), a strong inhibition
      of the reflex was observed whereas in the other seven subjects (subgroup 2) there
      was a strong facilitation of the reflex. All the subjects in both subgroups
      displayed similar decreases in the amplitude of late somatosensory evoked
      cerebral potentials during the hypnotic analgesia. No modification in the
      autonomic parameters or the EEG was observed. These data suggest that different
      strategies of modulation can be operative during effective hypnotic analgesia and
      that these are subject-dependent. Although all subjects may shift their attention
      away from the painful stimulus (which could explain the decrease of the late
      somatosensory evoked potentials), some of them inhibit their motor reaction to
      the stimulus at the spinal level, while in others, in contrast, this reaction is
      facilitated.

PMID- 9539678
TI  - Sympathetic vasoconstrictor reflex pattern in patients with complex regional pain
      syndrome.
AB  - Twenty patients suffering from complex regional pain syndrome (CRPS) and 21
      healthy control subjects were examined to evaluate sympathetic reflex
      vasoconstriction. The mean age of the 12 female and eight male patients was 48.9
      (21-72) years. At the time of investigation the median duration of the disease
      was 8.5 weeks (2-70). Twenty-one healthy subjects were investigated for control.
      Different maneuvers, such as the veno-arteriolar reflex (VAR), inspiratory gasp
      (IG), cold pressor test (CP) and mental arithmetic (MA), were employed to induce
      vasoconstriction while the cutaneous blood flow of the affected and the
      contralateral limb was recorded. In addition, the skin temperature of both limbs
      was measured by infrared thermography. In 14 of 20 patients and in 14 of 21
      control subjects vasoconstriction due to the provocation tests could be measured,
      while the remaining six patients and seven controls showed vasodilatation in at
      least one test, and by that they were excluded from analysis of vasoconstrictor
      reflex pattern. After thermoregulatory adaptation skin temperature was not
      different between the affected and the unaffected limb. Sympathetic reflex
      vasoconstriction triggered by MA which represents cortical generated, moderate
      vasoconstrictor stimulus, was significantly reduced on the affected limb (102.9%
      of prestimulus period) when compared to the control limb (85.0%, P < 0.002) or to
      controls (84.8%, P < 0.001). VAR (pure postganglionic), IG and CP (both spinal
      and supraspinal), representing stronger vasoconstrictor stimuli, revealed no
      significant side to side difference of sympathetic vasoconstriction and no
      significant difference as compared to controls. In conclusion our findings prove
      impairment of sympathetic vasoconstrictor activity after central vasoconstrictor
      stimulation in CRPS, and possible mechanisms are discussed.

PMID- 9539679
TI  - Reliability and factor structure of the Multidimensional Pain Inventory--Swedish
      Language Version (MPI-S).
AB  - The psychological assessment of chronic pain is often accomplished using
      questionnaires such as the (West Haven-Yale) Multidimensional Pain Inventory
      ((WHY)MPI) which is constructed to capture the multidimensionality of chronic
      pain. The (WHY)MPI theoretically originates from behavioural and cognitive
      behavioural theories of pain. It is divided into three parts and measures
      psychosocial and behavioural consequences of pain. This questionnaire has
      displayed satisfactory psychometric properties and translations of the original
      English version into German and Dutch have been demonstrated to be reliable and
      valid. The aim of this study was to test the reliability and factor structure of
      a Swedish translation of the (WHY)MPI, the MPI-S, and also to test the
      generalisability of the factor structure found for the (WHY)MPI. We performed
      analyses of internal consistency using Cronbach's alpha, and carried out a
      confirmatory factor analysis (CFA) employing LISREL-8 on a population of 682
      patients suffering from chronic musculoskeletal pain. Test-retest analysis was
      accomplished on a sub-sample of 54 individuals taken from the aforementioned
      population. For sections 1 and 2 of the MPI-S the overall reliability and
      stability were good, and after the exclusion of four items, the factor structure
      was similar to other versions of the MPI. For section 3, despite removal of five
      questions, the proposed factor structure could not be replicated. This part of
      the inventory is designed to measure the extent of different types of activities,
      and our results suggest that this section may only be used for assessing general
      activity level. We conclude that, with a few adjustments, the analyses yielded
      satisfactory results for sections 1 and 2 of the MPI-S regarding its factor
      structure, reliability and generalisability. For section 3 the hypothesised
      factor structure could not be confirmed.

PMID- 9539680
TI  - Cannabinoids reduce hyperalgesia and inflammation via interaction with peripheral
      CB1 receptors.
AB  - Central antinociceptive effects of cannabinoids have been well documented.
      However, relatively little is known about the peripheral effects of the
      cannabinoids on inflammation. In the present study, we evaluated the effects of
      peripherally administered cannabinoids on three indices of inflammation:
      carrageenan-induced thermal hyperalgesia, carrageenan-induced edema, and
      capsaicin-induced plasma extravasation. In addition, we determined the effect of
      cannabinoids on capsaicin-evoked neuropeptide release from isolated rat hindpaw
      skin. Our results indicate that cannabinoids produce antihyperalgesia via
      interaction with a peripheral CB1 receptor. Peripheral, but not systemic,
      administration of 0.01 ng anandamide inhibited the induction of hyperalgesia.
      Peripheral administration of anandamide also attenuated hyperalgesia after its
      development via interaction with the CB1 cannabinoid receptor subtype as
      indicated by its reversal with the CB1 receptor antagonist SR 141716A.
      Additionally, peripheral, but not systemic, administration of 0.01 ng anandamide
      inhibited edema. Peripherally administered cannabinoids also interacted with CB1
      receptors to inhibit capsaicin-evoked plasma extravasation into the hindpaw. One
      potential mechanism for the anti-inflammatory actions of the cannabinoids is the
      inhibition of neurosecretion from the peripheral terminals of nociceptive primary
      afferent fibers. This hypothesis is supported by the finding that anandamide
      inhibited capsaicin-evoked release of calcitonin gene-related peptide from
      isolated hindpaw skin. Collectively, these results indicate that cannabinoids
      reduce inflammation via interaction with a peripheral CB1 receptor. A potential
      mechanism for this effect is the inhibition of neurosecretion from capsaicin
      sensitive primary afferent fibers.

PMID- 9539681
TI  - Sex differences in temporal summation but not sensory-discriminative processing
      of thermal pain.
AB  - Gender differences in experimental pain sensitivity have been widely
      investigated, and the results generally indicate that females exhibit greater
      sensitivity to noxious stimuli than males. However, results using thermal pain
      procedures have been inconsistent, with some studies reporting greater responses
      among females and other studies reporting no gender differences. The present
      study investigated gender differences in thermal pain perception using several
      different psychophysical procedures. Twenty-seven females and 22 males underwent
      thermal testing, including: determination of thermal pain threshold and
      tolerance, a thermal discrimination procedure, real-time magnitude estimates of
      heat pulses, and temporal summation of thermal pain. The results indicated lower
      thermal pain threshold and tolerance and greater temporal summation of thermal
      pain among females, but no gender differences in thermal discrimination or real
      time magnitude estimates of discrete heat pulses. These findings suggest that
      gender differences in thermal pain perception may be more robust for sustained,
      temporally dynamic thermal stimuli with a strong C-fiber component.

PMID- 9539682
TI  - Genetic variance in nociception and its relationship to the potency of morphine
      induced analgesia in thermal and chemical tests.
AB  - The perceived intensity of a painful stimulus is determined in part by the
      stimulus intensity and environmental conditions. The purpose of this study was to
      determine the influence of genetic factors in nociception and its contribution to
      the potency of morphine to produce antinociception. Eight inbred strains of mice
      were tested across a range of stimulus intensities in thermal (hot plate) and
      chemical irritant (acetic acid) nociceptive tests. Stimulus intensities in the
      thermal test included hot plate temperatures of 51, 53, 55, 57 and 59 degrees C.
      Stimulus intensities in the chemical irritant test included acetic acid
      concentrations of 0.1, 0.3 and 0.6%. Linear interpolation of stimulus-effect
      curves revealed large genotype-dependent differences in the effective temperature
      resulting in a 10 s latency on the hot-plate (ET10") and the acetic acid
      concentration resulting in the same number of writhes as determined by the area
      under the curve (AUC50). There was no genetic correlation between sensitivity to
      thermal versus chemical stimuli. Morphine dose response curves were then
      determined at a fixed stimulus intensity in each test (55 degrees C and 0.6%
      acetic acid) to determine analgesic ED50 doses for each inbred strain. A
      significant effect of genotype on relative sensitivity to morphine-induced
      analgesia in both the thermal and chemical irritant tests was found, however
      there was no genetic correlation between the potency of morphine in each test.
      There was an inverse genetic correlation between sensitivity to thermal and
      chemical stimuli and morphine ED50 values in each respective test. In both tests,
      strains less sensitive to the nociceptive stimuli were more sensitive to the
      antinociceptive effects of morphine. Confirmation studies in a separate genetic
      population confirmed the inverse relationship between hot-plate sensitivity and
      antinociceptive potency. In summary, this study demonstrated (i) a large degree
      of genetically-determined variability in sensitivity to painful stimuli, (ii)
      sensitivity to thermal stimuli (hot-plate) is genetically unrelated to
      sensitivity to chemical (acetic acid) stimuli, (iii) the mechanism by which
      morphine produces its antinociceptive effects against thermal stimuli is largely
      genetically independent of the mechanism by which morphine produces its
      antinociceptive effects against chemical stimuli, and (iv) inherent differences
      in sensitivity to painful stimuli may be responsible, in part, for individual
      differences in the potency of morphine's antinociceptive effects.

PMID- 9539683
TI  - Excitotoxic spinal cord injury: behavioral and morphological characteristics of a
      central pain model.
AB  - Intraspinal injections of the AMPA-metabotropic receptor agonist quisqualic acid
      (QUIS) were made in an effort to simulate injury induced elevations of excitatory
      amino acids (EAAs), a well documented neurochemical change following spinal cord
      injury (SCI). The progressive pathological sequela associated with QUIS
      injections closely resembles the cascade of events described following ischemic
      and traumatic SCI and the pathogenesis of cavities in the clinical condition of
      post-traumatic syringomyelia. Using different injection parameters, i.e. depth
      and volume, to deliver QUIS into the cord the results have shown that the
      technique of intraspinal injection can be used to produce graded patterns of
      neuronal loss in specific regions of the spinal gray matter. Furthermore,
      neuronal loss in the dorsal horn, sparing the superficial laminae, results in the
      onset of spontaneous (excessive grooming behavior) and evoked (mechanical
      allodynia and thermal hyperalgesia) behaviors commonly associated with
      experimental models of chronic neuropathic pain. Thus, the present results
      provide a morphological correlate of spontaneous and evoked pain related
      behaviors following excitotoxic SCI. The behavioral characteristics combined with
      the similarities between QUIS induced injury and the clinical pathology of SCI
      support the use of the excitotoxic model in studies related to the central
      mechanism(s) of altered sensation, including pain, following spinal injury.

PMID- 9539684
TI  - Comment on Wall, PAIN, 71 (1997) 1-3.

PMID- 9539686
TI  - Comment on Weintraub, PAIN, 72 (1997) 284-285.

PMID- 9539685
TI  - Comment on Stein and Yassouridis, PAIN, 71 (1997) 119-121.

PMID- 9539687
TI  - Reply to Roberts and Kramis, PAIN, 72 (1997) 288-289.

PMID- 9539688
TI  - Comment on McQuay et al., PAIN, 68 (1996) 217-227.

PMID- 9539689
TI  - The "best" of cholesterols, the "worst" of cholesterols: a tale of two receptors.

PMID- 9539690
TI  - Swimming through the hydrophobic sea: new insights in protein translocation.

PMID- 9539691
TI  - Stability without a centromere.

PMID- 9539692
TI  - Long-term potentiation and the computational synapse.

PMID- 9539694
TI  - Exploiting circular DNA.

PMID- 9539695
TI  - Optimal prediction of underresolved dynamics.
AB  - A method is presented for computing the average solution of problems that are too
      complicated for adequate resolution, but where information about the statistics
      of the solution is available. The method involves computing average derivatives
      by interpolation based on linear regression, and an updating of a measure
      constrained by the available crude information. Examples are given.

PMID- 9539693
TI  - Dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) as
      neuroactive neurosteroids.

PMID- 9539696
TI  - Attempted hydrogen-deuterium exchange of the protio-trimethyloxonium dication
      (CH3)3OH2+, study of methylating ability of (CH3)3O+ in superacids and
      theoretical investigations.
AB  - Attempted hydrogen-deuterium exchange of trimethyloxonium ion, (CH3)3O+ with
      excess of 1:1 (2)HF/SbF5 superacid at -30 degreesC over a period of 30 days
      showed no exchange. Theoretical calculations at the MP2/6-31G** level are in
      accord with the lack of hydrogen-deuterium exchange in the methyl group of the
      (CH3)3O+ cation as protonation (protosolvation) prefers the oxygen lone pair of
      electrons, instead of a C---H bond. Methylation of aromatics with the
      (CH3)3O+CF3SO3- in CF3SO3H and 2CF3SO3H:B(O3SCF3)3 was also studied. Whereas in
      triflic acid no alkylation was observed, in triflatoboric acid, a powerful
      superacid, alkylation takes place, indicating protolytic activation of the
      trimethyloxonium ion.

PMID- 9539697
TI  - Structural requirements for 5-HT2A and 5-HT1A serotonin receptor potentiation by
      the biologically active lipid oleamide.
AB  - Oleamide is an endogenous fatty acid primary amide that possesses sleep-inducing
      properties in animals and that has been shown to effect serotonergic receptor
      responses and block gap junction communication. Herein, the potentiation of the 5
      HT1A receptor response is disclosed, and a study of the structural features of
      oleamide required for potentiation of the 5-HT2A and 5-HT1A response to serotonin
      (5-HT) is described. Of the naturally occurring fatty acids, the primary amide of
      oleic acid (oleamide) is the most effective at potentiating the 5-HT2A receptor
      response. The structural features required for activity were found to be highly
      selective. The presence, position, and stereochemistry of the delta9-cis double
      bond is required, and even subtle structural variations reduce or eliminate
      activity. Secondary or tertiary amides may replace the primary amide but follow a
      well defined relationship requiring small amide substituents, suggesting that the
      carboxamide serves as a hydrogen bond acceptor but not donor. Alternative
      modifications at the carboxamide as well as modifications of the methyl terminus
      or the hydrocarbon region spanning the carboxamide and double bond typically
      eliminate activity. A less extensive study of the 5-HT1A potentiation revealed
      that it is more tolerant and accommodates a wider range of structural
      modifications. An interesting set of analogs was identified that inhibit rather
      than potentiate the 5-HT2A, but not the 5-HT1A, receptor response, further
      suggesting that such analogs may permit the selective modulation of serotonin
      receptor subtypes and even have opposing effects on the different subtypes.

PMID- 9539698
TI  - Mapping strain exerted on blood vessel walls using deuterium double-quantum
      filtered MRI.
AB  - A technique is described for displaying distinct tissue layers of large blood
      vessel walls as well as measuring their mechanical strain. The technique is based
      on deuterium double-quantum-filtered (DQF) spectroscopic imaging. The
      effectiveness of the double-quantum filtration in suppressing the signal of bulk
      water is demonstrated on a phantom consisting of rat tail tendon fibers. Only
      intrafibrillar water is displayed, excluding all other signals of water molecules
      that reorient isotropically. One- and two-dimensional spectroscopic imaging of
      bovine aorta and coronary arteries show the characteristic DQF spectrum of each
      of the tissue layers. This property is used to obtain separate images of the
      outer layer, the tunica adventitia, or the intermediate layer, the tunica media,
      or both. To visualize the effect of elongation, the average residual quadrupole
      splitting <delta nu q> is calculated for each pixel. Two-dimensional deuterium
      quadrupolar splitting images are obtained for a fully relaxed and a 55% elongated
      sample of bovine coronary artery. These images indicate that the strong effect of
      strain is associated with water molecules in the tunica adventitia whereas the
      DQF NMR signal of water in the tunica media is apparently strain-insensitive.
      After appropriate calibration, these average quadrupolar splitting images can be
      interpreted as strain maps.

PMID- 9539699
TI  - A common-sense climate index: is climate changing noticeably?
AB  - We propose an index of climate change based on practical climate indicators such
      as heating degree days and the frequency of intense precipitation. We find that
      in most regions the index is positive, the sense predicted to accompany global
      warming. In a few regions, especially in Asia and western North America, the
      index indicates that climate change should be apparent already, but in most
      places climate trends are too small to stand out above year-to-year variability.
      The climate index is strongly correlated with global surface temperature, which
      has increased as rapidly as projected by climate models in the 1980s. We argue
      that the global area with obvious climate change will increase notably in the
      next few years. But we show that the growth rate of greenhouse gas climate
      forcing has declined in recent years, and thus there is an opportunity to keep
      climate change in the 21st century less than "business-as-usual" scenarios.

PMID- 9539700
TI  - Statistical analysis of shape through triangulation of landmarks: A study of
      sexual dimorphism in hominids.
AB  - Two objects with homologous landmarks are said to be of the same shape if the
      configuration of landmarks of one object can be exactly matched with that of the
      other by translation, rotation/reflection, and scaling. In an earlier paper, the
      authors proposed statistical analysis of shape by considering logarithmic
      differences of all possible Euclidean distances between landmarks. Tests of
      significance for differences in the shape of objects and methods of
      discrimination between populations were developed with such data. In the present
      paper, the corresponding statistical methodology is developed by triangulation of
      the landmarks and by considering the angles as natural measurements of shape.
      This method is applied to the study of sexual dimorphism in hominids.

PMID- 9539701
TI  - Plant terpenoid synthases: molecular biology and phylogenetic analysis.
AB  - This review focuses on the monoterpene, sesquiterpene, and diterpene synthases of
      plant origin that use the corresponding C10, C15, and C20 prenyl diphosphates as
      substrates to generate the enormous diversity of carbon skeletons characteristic
      of the terpenoid family of natural products. A description of the enzymology and
      mechanism of terpenoid cyclization is followed by a discussion of molecular
      cloning and heterologous expression of terpenoid synthases. Sequence relatedness
      and phylogenetic reconstruction, based on 33 members of the Tps gene family, are
      delineated, and comparison of important structural features of these enzymes is
      provided. The review concludes with an overview of the organization and
      regulation of terpenoid metabolism, and of the biotechnological applications of
      terpenoid synthase genes.

PMID- 9539702
TI  - A dimeric crystal structure for the N-terminal two domains of intercellular
      adhesion molecule-1.
AB  - The 3.0-A structure of a 190-residue fragment of intercellular adhesion molecule
      1 (ICAM-1, CD54) reveals two tandem Ig-superfamily (IgSF) domains. Each of two
      independent molecules dimerizes identically with a symmetry-related molecule over
      a hydrophobic interface on the BED sheet of domain 1, in agreement with
      dimerization of ICAM-1 on the cell surface. The residues that bind to the
      integrin LFA-1 are well oriented for bivalent binding in the dimer, with the
      critical Glu-34 residues pointing away from each other on the periphery. Residues
      that bind to rhinovirus are in the flexible BC and FG loops at the tip of domain
      1, and these and the upper half of domain 1 are well exposed in the dimer for
      docking to virus. By contrast, a residue important for binding to Plasmodium
      falciparum-infected erythrocytes is in the dimer interface. The presence of A'
      strands in both domains 1 and 2, conserved hydrogen bonds at domain junctions,
      and elaborate hydrogen bond networks around the key integrin binding residues in
      domain 1 make these domains suited to resist tensile forces during adhesive
      interactions. A subdivision of the intermediate (I) set of IgSF domains is
      proposed in which domain 1 of ICAM-1 and previously described I set domains
      belong to the I1 set and domain 2 of ICAM-1, ICAM-2, and vascular cell adhesion
      molecule-1 belong to the I2 set.

PMID- 9539703
TI  - The structure of the two amino-terminal domains of human ICAM-1 suggests how it
      functions as a rhinovirus receptor and as an LFA-1 integrin ligand.
AB  - The normal function of human intercellular adhesion molecule-1 (ICAM-1) is to
      provide adhesion between endothelial cells and leukocytes after injury or stress.
      ICAM-1 binds to leukocyte function-associated antigen (LFA-1) or macrophage-1
      antigen (Mac-1). However, ICAM-1 is also used as a receptor by the major group of
      human rhinoviruses and is a catalyst for the subsequent viral uncoating during
      cell entry. The three-dimensional atomic structure of the two amino-terminal
      domains (D1 and D2) of ICAM-1 has been determined to 2.2-A resolution and fitted
      into a cryoelectron microscopy reconstruction of a rhinovirus-ICAM-1 complex.
      Rhinovirus attachment is confined to the BC, CD, DE, and FG loops of the amino
      terminal Ig-like domain (D1) at the end distal to the cellular membrane. The
      loops are considerably different in structure to those of human ICAM-2 or murine
      ICAM-1, which do not bind rhinoviruses. There are extensive charge interactions
      between ICAM-1 and human rhinoviruses, which are mostly conserved in both major
      and minor receptor groups of rhinoviruses. The interaction of ICAMs with LFA-1 is
      known to be mediated by a divalent cation bound to the insertion (I)-domain on
      the alpha chain of LFA-1 and the carboxyl group of a conserved glutamic acid
      residue on ICAMs. Domain D1 has been docked with the known structure of the I
      domain. The resultant model is consistent with mutational data and provides a
      structural framework for the adhesion between these molecules.

PMID- 9539704
TI  - Effect of mutating the regulatory phosphoserine and conserved threonine on the
      activity of the expressed catalytic domain of Acanthamoeba myosin I heavy chain
      kinase.
AB  - Phosphorylation of Ser-627 is both necessary and sufficient for full activity of
      the expressed 35-kDa catalytic domain of myosin I heavy chain kinase (MIHCK). Ser
      627 lies in the variable loop between highly conserved residues DFG and APE at a
      position at which a phosphorylated Ser/Thr also occurs in many other Ser/Thr
      protein kinases. The variable loop of MIHCK contains two other hydroxyamino
      acids: Thr-631, which is conserved in almost all Ser/Thr kinases, and Thr-632,
      which is not conserved. We determined the effects on the kinase activity of the
      expressed catalytic domain of mutating Ser-627, Thr-631, and Thr-632 individually
      to Ala, Asp, and Glu. The S627A mutant was substantially less active than wild
      type (wt), with a lower kcat and higher Km for both peptide substrate and ATP,
      but was more active than unphosphorylated wt. The S627D and S627E mutants were
      also less active than phosphorylated wt, i.e., acidic amino acids cannot
      substitute for phospho-Ser-627. The activity of the T631A mutant was as low as
      that of the S627A mutant, whereas the T632A mutant was as active as
      phosphorylated wt, indicating that highly conserved Thr-631, although not
      phosphorylated, is essential for catalytic activity. Asp and Glu substitutions
      for Thr-631 and Thr-632 were inhibitory to various degrees. Molecular modeling
      indicated that Thr-631 can hydrogen bond with conserved residue Asp-591 in the
      catalytic loop and that similar interactions are possible for other kinases whose
      activities also are regulated by phosphorylation in the variable loop. Thus, this
      conserved Thr residue may be essential for the activities of other Ser/Thr
      protein kinases as well as for the activity of MIHCK.

PMID- 9539705
TI  - The C-terminal SET domains of ALL-1 and TRITHORAX interact with the INI1 and SNR1
      proteins, components of the SWI/SNF complex.
AB  - The ALL-1 gene was discovered by virtue of its involvement in human acute
      leukemia. Its Drosophila homolog trithorax (trx) is a member of the trx-Polycomb
      gene family, which maintains correct spatial expression of the Antennapedia and
      bithorax complexes during embryogenesis. The C-terminal SET domain of ALL-1 and
      TRITHORAX (TRX) is a 150-aa motif, highly conserved during evolution. We
      performed yeast two hybrid screening of Drosophila cDNA library and detected
      interaction between a TRX polypeptide spanning SET and the SNR1 protein. SNR1 is
      a product of snr1, which is classified as a trx group gene. We found parallel
      interaction in yeast between the SET domain of ALL-1 and the human homolog of
      SNR1, INI1 (hSNF5). These results were confirmed by in vitro binding studies and
      by demonstrating coimmunoprecipitation of the proteins from cultured cells and/or
      transgenic flies. Epitope-tagged SNR1 was detected at discrete sites on larval
      salivary gland polytene chromosomes, and these sites colocalized with around one
      half of TRX binding sites. Because SNR1 and INI1 are constituents of the SWI/SNF
      complex, which acts to remodel chromatin and consequently to activate
      transcription, the interactions we observed suggest a mechanism by which the
      SWI/SNF complex is recruited to ALL-1/trx targets through physical interactions
      between the C-terminal domains of ALL-1 and TRX and INI1/SNR1.

PMID- 9539706
TI  - Role of a critical water in scytalone dehydratase-catalyzed reaction.
AB  - Scytalone dehydratase (EC 4.2.1.94) catalyzes the dehydration of two important
      intermediates in the biosynthesis of melanin, and it functions without metal ions
      or any cofactors. Using molecular orbital theory, we have examined the role of a
      critical water molecule in the mechanism of scytalone dehydratase. The water,
      together with an internal hydrogen bonding, contributes significantly to the
      stabilization of the transition state (or the enolate intermediate). The role of
      two active site tyrosines (Tyr-50 and Tyr-30) is (i) to hold the critical water
      in place so that it may stabilize the transition state without much structural
      rearrangement during the catalytic reaction, and (ii) to polarize the water,
      making it a better general acid. The stereochemistry of the scytalone dehydratase
      catalyzed dehydration is also discussed.

PMID- 9539707
TI  - Disruption of cellular translational control by a viral truncated eukaryotic
      translation initiation factor 2alpha kinase homolog.
AB  - Phosphorylation of eukaryotic translation initiation factor 2alpha (eIF2alpha) is
      a common cellular mechanism to limit protein synthesis in stress conditions.
      Baculovirus PK2, which resembles the C-terminal half of a protein kinase domain,
      was found to inhibit both human and yeast eIF2alpha kinases. Insect cells
      infected with wild-type, but not pk2-deleted, baculovirus exhibited reduced
      eIF2alpha phosphorylation and increased translational activity. The negative
      regulatory effect of human protein kinase RNA-regulated (PKR), an eIF2alpha
      kinase, on virus production was counteracted by PK2, indicating that
      baculoviruses have evolved a unique strategy for disrupting a host stress
      response. PK2 was found in complex with PKR and blocked kinase
      autophosphorylation in vivo, suggesting a mechanism of kinase inhibition mediated
      by interaction between truncated and intact kinase domains.

PMID- 9539709
TI  - Mass spectrometric and capillary electrophoretic investigation of the enzymatic
      degradation of heparin-like glycosaminoglycans.
AB  - Difficulties in determining composition and sequence of glycosaminoglycans, such
      as those related to heparin, have limited the investigation of these biologically
      important molecules. Here, we report methodology, based on matrix-assisted laser
      desorption ionization MS and capillary electrophoresis, to follow the time course
      of the enzymatic degradation of heparin-like glycosaminoglycans through the
      intermediate stages to the end products. MS allows the determination of the
      molecular weights of the sulfated carbohydrate intermediates and their
      approximate relative abundances at different time points of the experiment.
      Capillary electrophoresis subsequently is used to follow more accurately the
      abundance of the components and also to measure sulfated disaccharides for which
      MS is not well applicable. For those substrates that produce identical or
      isomeric intermediates, the reducing end of the carbohydrate chain was converted
      to the semicarbazone. This conversion increases the molecular weight of all
      products retaining the reducing terminus by the "mass tag" (in this case 56 Da)
      and thus distinguishes them from other products. A few picomoles of heparin
      derived, sulfated hexa- to decasaccharides of known structure were subjected to
      heparinase I digestion and analyzed. The results indicate that the enzyme acts
      primarily exolytically and in a processive mode. The methodology described should
      be equally useful for other enzymes, including those modified by site-directed
      mutagenesis, and may lead to the development of an approach to the sequencing of
      complex glycosaminoglycans.

PMID- 9539708
TI  - Identification of a nucleotide binding site in HIV-1 integrase.
AB  - HIV-1 integrase is essential for viral replication and can be inhibited by
      antiviral nucleotides. Photoaffinity labeling with the 3'-azido-3'-deoxythymidine
      (AZT) analog 3',5-diazido-2', 3'-dideoxyuridine 5'-monophosphate (5N3-AZTMP) and
      proteolytic mapping identified the amino acid 153-167 region of integrase as the
      site of photocrosslinking. Docking of 5N3-AZTMP revealed the possibility for
      strong hydrogen bonds between the inhibitor and lysines 156, 159, and 160 of the
      enzyme. Mutation of these residues reduced photocrosslinking selectively. This
      report elucidates the binding site of a nucleotide inhibitor of HIV-1 integrase,
      and possibly a component of the enzyme polynucleotide binding site.

PMID- 9539710
TI  - Direct evidence for a predominantly exolytic processive mechanism for
      depolymerization of heparin-like glycosaminoglycans by heparinase I.
AB  - Heparinase I from Flavobacterium heparinum has important uses for elucidating the
      complex sequence heterogeneity of heparin-like glycosaminoglycans (HLGAGs).
      Understanding the biological function of HLGAGs has been impaired by the limited
      methods for analysis of pure or mixed oligosaccharide fragments. Here, we use
      methodologies involving MS and capillary electrophoresis to investigate the
      sequence of events during heparinase I depolymerization of HLGAGs. In an initial
      step, heparinase I preferentially cleaves exolytically at the nonreducing
      terminal linkage of the HLGAG chain, although it also cleaves internal linkages
      at a detectable rate. In a second step, heparinase I has a strong preference for
      cleaving the same substrate molecule processively, i.e., to cleave the next site
      toward the reducing end of the HLGAG chain. Computer simulation showed that the
      experimental results presented here from analysis of oligosaccharide degradation
      were consistent with literature data for degradation of polymeric HLGAG by
      heparinase I. This study presents direct evidence for a predominantly exolytic
      and processive mechanism of depolymerization of HLGAG by heparinase I.

PMID- 9539711
TI  - The human U5-200kD DEXH-box protein unwinds U4/U6 RNA duplices in vitro.
AB  - Splicing of nuclear precursors of mRNA (pre-mRNA) involves dynamic interactions
      between the RNA constituents of the spliceosome. The rearrangement of RNA-RNA
      interactions, such as the unwinding of the U4/U6 duplex, is believed to be driven
      by ATP-dependent RNA helicases. We recently have shown that spliceosomal U5 small
      nuclear ribonucleoproteins (snRNPs) from HeLa cells contain two proteins, U5
      200kD and U5-100kD, which share homology with the DEAD/DEXH-box families of RNA
      helicases. Here we demonstrate that purified U5 snRNPs exhibit ATP-dependent
      unwinding of U4/U6 RNA duplices in vitro. To identify the protein responsible for
      this activity, U5 snRNPs were depleted of a subset of proteins under high salt
      concentrations and assayed for RNA unwinding. The activity was retained in U5
      snRNPs that contain the U5-200kD protein but lack U5-100kD, suggesting that the
      U5-200kD protein could mediate U4/U6 duplex unwinding. Finally, U5-200kD was
      purified to homogeneity by glycerol gradient centrifugation of U5 snRNP proteins
      in the presence of sodium thiocyanate, followed by ion exchange chromatography.
      The RNA unwinding activity was found to reside exclusively with the U5-200kD DEXH
      box protein. Our data raise the interesting possibility that this RNA helicase
      catalyzes unwinding of the U4/U6 RNA duplex in the spliceosome.

PMID- 9539712
TI  - The underlying pathway structure of biochemical reaction networks.
AB  - Bioinformatics is yielding extensive, and in some cases complete, genetic and
      biochemical information about individual cell types and cellular processes,
      providing the composition of living cells and the molecular structure of its
      components. These components together perform integrated cellular functions that
      now need to be analyzed. In particular, the functional definition of biochemical
      pathways and their role in the context of the whole cell is lacking. In this
      study, we show how the mass balance constraints that govern the function of
      biochemical reaction networks lead to the translation of this problem into the
      realm of linear algebra. The functional capabilities of biochemical reaction
      networks, and thus the choices that cells can make, are reflected in the null
      space of their stoichiometric matrix. The null space is spanned by a finite
      number of basis vectors. We present an algorithm for the synthesis of a set of
      basis vectors for spanning the null space of the stoichiometric matrix, in which
      these basis vectors represent the underlying biochemical pathways that are
      fundamental to the corresponding biochemical reaction network. In other words,
      all possible flux distributions achievable by a defined set of biochemical
      reactions are represented by a linear combination of these basis pathways. These
      basis pathways thus represent the underlying pathway structure of the defined
      biochemical reaction network. This development is significant from a fundamental
      and conceptual standpoint because it yields a holistic definition of biochemical
      pathways in contrast to definitions that have arisen from the historical
      development of our knowledge about biochemical processes. Additionally, this new
      conceptual framework will be important in defining, characterizing, and studying
      biochemical pathways from the rapidly growing information on cellular function.

PMID- 9539713
TI  - Control of phosphatidylserine biosynthesis through phosphatidylserine-mediated
      inhibition of phosphatidylserine synthase I in Chinese hamster ovary cells.
AB  - Phosphatidylserine (PtdSer) synthesis in Chinese hamster ovary (CHO) cells occurs
      through the exchange of L-serine with the base moiety of phosphatidylcholine or
      phosphatidylethanolamine. The synthesis is depressed on the addition of PtdSer to
      the culture medium. A CHO cell mutant named mutant 29, whose PtdSer biosynthesis
      is highly resistant to this depression by exogenous PtdSer, has been isolated
      from CHO-K1 cells. In the present study, the PtdSer-resistant PtdSer biosynthesis
      in the mutant was traced to a point mutation in the PtdSer synthase I gene, pssA,
      resulting in the replacement of Arg-95 of the synthase by lysine. Introduction of
      the mutant pssA cDNA, but not the wild-type pssA cDNA, into CHO-K1 cells induced
      the PtdSer-resistant PtdSer biosynthesis. In a cell-free system, the serine base
      exchange activity of the wild-type pssA-transfected cells was inhibited by
      PtdSer, but that of the mutant pssA-transfected cells was resistant to the
      inhibition. Like the mutant 29 cells, the mutant pssA-transfected cells grown
      without exogenous PtdSer exhibited an approximately 2-fold increase in the
      cellular PtdSer level compared with that in CHO-K1 cells, although the wild-type
      pssA-transfected cells did not exhibit such a significant increase. These results
      indicated that the inhibition of PtdSer synthase I by PtdSer is essential for the
      maintenance of a normal PtdSer level in CHO-K1 cells and that Arg-95 of the
      synthase is a crucial residue for the inhibition.

PMID- 9539714
TI  - Brefeldin A-inhibited guanine nucleotide-exchange activity of Sec7 domain from
      yeast Sec7 with yeast and mammalian ADP ribosylation factors.
AB  - The Saccharomyces cerevisiae Sec7 protein (ySec7p), which is an important
      component of the yeast secretory pathway, contains a sequence of approximately
      200 amino acids referred to as a Sec7 domain. Similar Sec7 domain sequences have
      been recognized in several guanine nucleotide-exchange proteins (GEPs) for ADP
      ribosylation factors (ARFs). ARFs are approximately 20-kDa GTPases that regulate
      intracellular vesicular membrane trafficking and activate phospholipase D. GEPs
      activate ARFs by catalyzing the replacement of bound GDP with GTP. We, therefore,
      undertook to determine whether a Sec7 domain itself could catalyze nucleotide
      exchange on ARF and found that it exhibited brefeldin A (BFA)-inhibitable ARF GEP
      activity. BFA is known to inhibit ARF GEP activity in Golgi membranes, thereby
      causing reversible apparent dissolution of the Golgi complex in many cells. The
      His6-tagged Sec7 domain from ySec7p (rySec7d) synthesized in Escherichia coli
      enhanced binding of guanosine 5'-[gamma-[35S]thio]triphosphate by recombinant
      yeast ARF1 (ryARF1) and ryARF2 but not by ryARF3. The effects of rySec7d on
      ryARF2 were inhibited by BFA in a concentration-dependent manner but not by
      inactive analogues of BFA (B-17, B-27, and B-36). rySec7d also promoted BFA
      sensitive guanosine 5'-[gamma-thio]triphosphate binding by nonmyristoylated
      recombinant human ARF1 (rhARF1), rhARF5, and rhARF6, although the effect on
      rhARF6 was very small. These results are consistent with the conclusion that the
      yeast Sec7 domain itself contains the elements necessary for ARF GEP activity and
      its inhibition by BFA.

PMID- 9539715
TI  - Light-induced expression of fatty acid desaturase genes.
AB  - In cyanobacterial cells, fatty acid desaturation is one of the crucial steps in
      the acclimation processes to low-temperature conditions. The expression of all
      the four acyl lipid desaturase genes of Synechocystis PCC 6803 was studied as a
      function of temperature and separately as a function of light. We used cells
      grown at 25 degreesC in light-activated heterotrophic growth conditions. In these
      cells, the production of alpha-linolenic acid and 18:4 fatty acids was negligible
      and the synthesis of gamma-linolenic acid was remarkably suppressed compared with
      those of the cells grown photoautotrophically. The cells grown in the light in
      the presence of glucose showed no difference in fatty acid composition compared
      with cells grown photoautotrophically. The level of desC mRNA for delta9
      desaturase was not affected by either the temperature or the light. It was
      constitutively expressed at 25 degreesC with and without illumination. The level
      of desB transcripts was negligible in the dark-grown cells and was enhanced about
      10-fold by exposure of the cells to light. The maximum level of expression
      occurred within 15 min. The level of desA and desD mRNAs was higher in dark-grown
      cells than that of desB mRNA for omega3 desaturase. However, the induction of
      both desA and desD mRNAs for delta12 and delta6 desaturases, respectively, was
      enhanced by light about 10-fold. Rifampicin, chloramphenicol, and 3-(3, 4
      dichlorophenyl)-1,1-dimethylurea completely blocked the induction of the
      expression of desA, desB, and desD. Consequently, we suggest the regulatory role
      of light via photosynthetic processes in the induction of the expression of acyl
      lipid desaturases.

PMID- 9539716
TI  - A single-headed dimer of Escherichia coli ribosomal protein L7/L12 supports
      protein synthesis.
AB  - During protein synthesis, the two elongation factors Tu and G alternately bind to
      the 50S ribosomal subunit at a site of which the protein L7/L12 is an essential
      component. L7/L12 is present in each 50S subunit in four copies organized as two
      dimers. Each dimer consists of distinct domains: a single N-terminal ("tail")
      domain that is responsible for both dimerization and binding to the ribosome via
      interaction with the protein L10 and two independent globular C-terminal domains
      ("heads") that are required for binding of elongation factors to ribosomes. The
      two heads are connected by flexible hinge sequences to the N-terminal domain.
      Important questions concerning the mechanism by which L7/L12 interacts with
      elongation factors are posed by us in response to the presence of two dimers, two
      heads per dimer, and their dynamic, mobile properties. In an attempt to answer
      these questions, we constructed a single-headed dimer of L7/L12 by using
      recombinant DNA techniques and chemical cross-linking. This chimeric molecule was
      added to inactive core particles lacking wild-type L7/L12 and shown to restore
      activity to a level approaching that of wild-type two-headed L7/L12.

PMID- 9539717
TI  - Telomere loss in cells treated with cisplatin.
AB  - Telomeres play an important role in the immortalization of proliferating cells.
      The long tandem repeats of 5'-TTAGGG-3' sequences in human telomeres are
      potential targets for the anticancer drug cisplatin, which forms mainly
      intrastrand d(GpG) and d(ApG) cross-links on DNA. The present study reveals that
      telomeres in cisplatin-treated HeLa cells are markedly shortened and degraded. A
      dose that killed 61% of the cells but allowed one round of cell division resulted
      in shortened telomeres before the induction of apoptosis. Higher doses of
      cisplatin halted cell cycle progression during the first S phase and triggered
      apoptosis followed by degradation of telomere repeats. A model in which both cell
      division with incomplete replication and induction of apoptosis by cisplatin
      could occur was devised to explain the drug-induced telomere loss.

PMID- 9539718
TI  - Amyloid fibril formation by an SH3 domain.
AB  - The SH3 domain is a well characterized small protein module with a simple fold
      found in many proteins. At acid pH, the SH3 domain (PI3-SH3) of the p85alpha
      subunit of bovine phosphatidylinositol 3-kinase slowly forms a gel that consists
      of typical amyloid fibrils as assessed by electron microscopy, a Congo red
      binding assay, and x-ray fiber diffraction. The soluble form of PI3-SH3 at acid
      pH (the A state by a variety of techniques) from which fibrils are generated has
      been characterized. Circular dichroism in the far- and near-UV regions and 1H NMR
      indicate that the A state is substantially unfolded relative to the native
      protein at neutral pH. NMR diffusion measurements indicate, however, that the
      effective hydrodynamic radius of the A state is only 23% higher than that of the
      native protein and is 20% lower than that of the protein denatured in 3.5 M
      guanidinium chloride. In addition, the A state binds the hydrophobic dye 1
      anilinonaphthalene-8-sulfonic acid, which suggests that SH3 in this state has a
      partially formed hydrophobic core. These results indicate that the A state is
      partially folded and support the hypothesis that partially folded states formed
      in solution are precursors of amyloid deposition. Moreover, that this domain
      aggregates into amyloid fibrils suggests that the potential for amyloid
      deposition may be a common property of proteins, and not only of a few proteins
      associated with disease.

PMID- 9539719
TI  - Manipulation of the membrane binding site of vitamin K-dependent proteins:
      enhanced biological function of human factor VII.
AB  - Recent studies suggested that modification of the membrane contact site of
      vitamin K-dependent proteins may enhance the membrane affinity and function of
      members of this protein family. The properties of a factor VII mutant, factor VII
      Q10E32, relative to wild-type factor VII (VII, containing P10K32), have been
      compared. Membrane affinity of VII-Q10E32 was about 20-fold higher than that of
      wild-type factor VII. The rate of autoactivation VII-Q10E32 with soluble tissue
      factor was 100-fold faster than wild-type VII and its rate of activation by
      factor Xa was 30 times greater than that of wild-type factor VII. When combined
      with soluble tissue factor and phospholipid, activated factor VII-Q10E32
      displayed increased activation of factor X. Its coagulant activity was enhanced
      in all types of plasma and with all sources of tissue factor tested. This
      difference in activity (maximum 50-fold) was greatest when coagulation conditions
      were minimal, such as limiting levels of tissue factor and/or phospholipid.
      Because of its enhanced activity, factor VII-Q10E32 and its derivatives may
      provide important reagents for research and may be more effective in treatment of
      bleeding and/or clotting disorders.

PMID- 9539720
TI  - In vivo function of mutated spliced leader RNAs in Caenorhabditis elegans.
AB  - The role of spliced leader RNA (SL RNA) in trans-splicing in Caenorhabditis
      elegans has been studied through a combination of in vitro mutagenesis and in
      vivo complementation of rrs-1 mutant nematodes, which lack endogenous SL1 RNA.
      Three classes of mutant SL1 RNAs have been found-those that rescue the lethal
      phenotype at low concentration of transforming DNA, those that rescue at high but
      not low concentration, and those that do not rescue at all. These studies showed
      that some mutations in the otherwise highly conserved 22-nt spliced leader are
      tolerated for splicing and post-splicing events. A longer spliced leader also can
      be tolerated but only when present in high copy number. Changes in the first 16
      nucleotides result in the appearance of no SL RNA, consistent with the in vitro
      studies by others showing that the SL1 RNA promoter partly resides within the
      spliced leader sequence.

PMID- 9539721
TI  - DnaA-stimulated transcriptional activation of orilambda: Escherichia coli RNA
      polymerase beta subunit as a transcriptional activator contact site.
AB  - We present evidence that Escherichia coli RNA polymerase beta subunit may be a
      transcriptional activator contact site. Stimulation of the activity of the pR
      promoter by DnaA protein is necessary for replication of plasmids derived from
      bacteriophage lambda. We found that DnaA activates the pR promoter in vitro.
      Particular mutations in the rpoB gene were able to suppress negative effects that
      certain dnaA mutations had on the replication of lambda plasmids; this
      suppression was allele-specific. When a potential DnaA-binding sequence located
      several base pairs downstream of the pR promoter was scrambled by in vitro
      mutagenesis, the pR promoter was no longer activated by DnaA both in vivo and in
      vitro. Therefore, we conclude that DnaA may contact the beta subunit of RNA
      polymerase during activation of the pR promoter. A new classification of
      prokaryotic transcriptional activators is proposed.

PMID- 9539722
TI  - A novel glutamine-RNA interaction identified by screening libraries in mammalian
      cells.
AB  - The arginine-rich motif provides a versatile framework for RNA recognition in
      which few amino acids other than arginine are needed to mediate specific binding.
      Using a mammalian screening system based on transcriptional activation by HIV
      Tat, we identified novel arginine-rich peptides from combinatorial libraries that
      bind tightly to the Rev response element of HIV. Remarkably, a single glutamine,
      but not asparagine, within a stretch of polyarginine can mediate high-affinity
      binding. These results, together with the structure of a Rev peptide-Rev response
      element complex, suggest that the carboxamide groups of glutamine or asparagine
      are well-suited to hydrogen bond to G-A base pairs and begin to establish an RNA
      recognition code for the arginine-rich motif. The screening approach may provide
      a relatively general method for screening expression libraries in mammalian
      cells.

PMID- 9539723
TI  - The C terminus of beta-tubulin regulates vinblastine-induced tubulin
      polymerization.
AB  - Oligoanions such as sodium triphosphate or GTP prevent and/or reverse vinblastine
      induced polymerization of tubulin. We now show that the anions of glutamate-rich
      extreme C termini of tubulin are similarly involved in the regulation of the
      vinblastine effect. Cleavage of the C termini by limited proteolysis with
      subtilisin enhances vinblastine-induced tubulin polymerization and abolishes the
      anion effect. Only the beta-tubulin C terminus needs to be removed to achieve
      these changes and the later cleavage of the alpha-tubulin C terminus has little
      additional effect. In fact, vinblastine concentrations >20 microM block cleavage
      of the alpha-tubulin C terminus in the polymer, whereas cleavage of the beta
      tubulin C terminus proceeds unimpeded over the time used. The vinblastine effect
      on tubulin polymerization is also highly pH-dependent between pH 6.5 and 7.5;
      this is less marked, but not absent, after subtilisin treatment. A working model
      is proposed wherein an anionic domain proximal to the extreme C terminus must
      interact with a cationic domain to permit vinblastine to promote polymerization.
      Both exogenous and extreme C-terminal anions compete for the cationic domain with
      the proximal anionic domain to prevent vinblastine-induced polymerization. We
      conclude that the electrostatic regulation of tubulin polymerization induced by
      vinblastine resides primarily in the beta-tubulin C terminus but that additional
      regulation proximal in the tubulin molecule also plays a role.

PMID- 9539724
TI  - Polymerase recognition of synthetic oligodeoxyribonucleotides incorporating
      degenerate pyrimidine and purine bases.
AB  - A universal base that is capable of substituting for any of the four natural
      bases in DNA would be of great utility in both mutagenesis and recombinant DNA
      experiments. This paper describes the properties of oligonucleotides
      incorporating two degenerate bases, the pyrimidine base 6H,8H-3,4
      dihydropyrimido[4,5-c][1,2]oxazin-7-one and the purine base N6-methoxy-2,6
      diaminopurine, designated P and K, respectively. An equimolar mixture of the
      analogues P and K (called M) acts, in primers, as a universal base. The thermal
      stability of oligonucleotide duplexes were only slightly reduced when natural
      bases were replaced by P or K. Templates containing the modified bases were
      copied by Taq polymerase; P behaved as thymine in 60% of copying events and as
      cytosine in 40%, whereas K behaved as if it were guanine (13%) or adenine (87%).
      The dUTPase gene of Caenorhabditis elegans, which we have found to contain three
      nonidentical homologous repeats, was used as a model system to test the use of
      these bases in primers for DNA synthesis. A pair of oligodeoxyribonucleotides,
      each 20 residues long and containing an equimolar mixture of P and K at six
      positions, primed with high specificity both T7 DNA polymerase in sequencing
      reactions and Taq polymerase in PCRs; no nonspecific amplification was obtained
      on genomic DNA of C. elegans. Use of P and K can significantly reduce the
      complexity of degenerate oligonucleotide mixtures, and when used together, P and
      K can act as a universal base.

PMID- 9539725
TI  - The TOR (target of rapamycin) signal transduction pathway regulates the stability
      of translation initiation factor eIF4G in the yeast Saccharomyces cerevisiae.
AB  - Initiation factor eIF4G is an essential protein required for initiation of mRNA
      translation via the 5' cap-dependent pathway. It interacts with eIF4E (the mRNA
      5' cap-binding protein) and serves as an anchor for the assembly of further
      initiation factors. With treatment of Saccharomyces cerevisiae with rapamycin or
      with entry of cells into the diauxic phase, eIF4G is rapidly degraded, whereas
      initiation factors eIF4E and eIF4A remain stable. We propose that nutritional
      deprivation or interruption of the TOR signal transduction pathway induces eIF4G
      degradation.

PMID- 9539726
TI  - Light-activated rhodopsin induces structural binding motif in G protein alpha
      subunit.
AB  - A large superfamily of transmembrane receptors control cellular responses to
      diverse extracellular signals by catalyzing activation of specific types of
      heterotrimeric GTP-binding proteins. How these receptors recognize and promote
      nucleotide exchange on G protein alpha subunits to initiate signal amplification
      is unknown. The three-dimensional structure of the transducin (Gt) alpha subunit
      C-terminal undecapeptide Gtalpha(340-350) IKENLKDCGLF was determined by
      transferred nuclear Overhauser effect spectroscopy while it was bound to
      photoexcited rhodopsin. Light activation of rhodopsin causes a dramatic shift
      from a disordered conformation of Gtalpha(340-350) to a binding motif with a
      helical turn followed by an open reverse turn centered at Gly-348, a helix
      terminating C capping motif of an alphaL type. Docking of the NMR structure to
      the GDP-bound x-ray structure of Gt reveals that photoexcited rhodopsin promotes
      the formation of a continuous helix over residues 325-346 terminated by the C
      terminal helical cap with a unique cluster of crucial hydrophobic side chains. A
      molecular mechanism by which activated receptors can control G proteins through
      reversible conformational changes at the receptor-G protein interface is
      demonstrated.

PMID- 9539727
TI  - The role of enzyme distortion in the single displacement mechanism of family 19
      chitinases.
AB  - By using molecular dynamics simulations, we have examined the binding of a
      hexaNAG substrate and two potential hydrolysis intermediates (an oxazoline ion
      and an oxocarbenium ion) to a family 19 barley chitinase. We find the hexaNAG
      substrate binds with all sugars in a chair conformation, unlike the family 18
      chitinase which causes substrate distortion. Glu 67 is in a position to protonate
      the anomeric oxygen linking sugar residues D and E whereas Asn 199 serves to
      hydrogen bond with the C2' N-acetyl group of sugar D, thus preventing the
      formation of an oxazoline ion intermediate. In addition, Glu 89 is part of a
      flexible loop region allowing a conformational change to occur within the active
      site to bring the oxocarbenium ion intermediate and Glu 89 closer by 4-5 A. A
      hydrolysis product with inversion of the anomeric configuration occurs because of
      nucleophilic attack by a water molecule that is coordinated by Glu 89 and Ser
      120. Issues important for the design of inhibitors specific to family 19
      chitinases over family 18 chitinases also are discussed.

PMID- 9539728
TI  - Membrane-bound state of the colicin E1 channel domain as an extended two
      dimensional helical array.
AB  - Atomic level structures have been determined for the soluble forms of several
      colicins and toxins, but the structural changes that occur after membrane binding
      have not been well characterized. Changes occurring in the transition from the
      soluble to membrane-bound state of the C-terminal 190-residue channel polypeptide
      of colicin E1 (P190) bound to anionic membranes are described. In the membrane
      bound state, the alpha-helical content increases from 60-64% to 80-90%, with a
      concomitant increase in the average length of the helical segments from 12 to 16
      or 17 residues, close to the length required to span the membrane bilayer in the
      open channel state. The average distance between helical segments is increased
      and interhelix interactions are weakened, as shown by a major loss of tertiary
      structure interactions, decreased efficiency of fluorescence resonance energy
      transfer from an energy donor on helix V of P190 to an acceptor on helix IX, and
      decreased resonance energy transfer at higher temperatures, not observed in
      soluble P190, implying freedom of motion of helical segments. Weaker interactions
      are also shown by a calorimetric thermal transition of low cooperativity, and the
      extended nature of the helical array is shown by a 3- to 4-fold increase in the
      average area subtended per molecule to 4,200 A2 on the membrane surface. The
      latter, with analysis of the heat capacity changes, implies the absence of a
      developed hydrophobic core in the membrane-bound P190. The membrane interfacial
      layer thus serves to promote formation of a highly helical extended two
      dimensional flexible net. The properties of the membrane-bound state of the
      colicin channel domain (i.e., hydrophobic anchor, lengthened and loosely coupled
      alpha-helices, and close association with the membrane interfacial layer) are
      plausible structural features for the state that is a prerequisite for voltage
      gating, formation of transmembrane helices, and channel opening.

PMID- 9539729
TI  - Brownian dynamics simulations of protein folding: access to milliseconds time
      scale and beyond.
AB  - Protein folding occurs on a time scale ranging from milliseconds to minutes for a
      majority of proteins. Computer simulation of protein folding, from a random
      configuration to the native structure, is nontrivial owing to the large disparity
      between the simulation and folding time scales. As an effort to overcome this
      limitation, simple models with idealized protein subdomains, e.g., the diffusion
      collision model of Karplus and Weaver, have gained some popularity. We present
      here new results for the folding of a four-helix bundle within the framework of
      the diffusion-collision model. Even with such simplifying assumptions, a direct
      application of standard Brownian dynamics methods would consume 10,000 processor
      years on current supercomputers. We circumvent this difficulty by invoking a
      special Brownian dynamics simulation. The method features the calculation of the
      mean passage time of an event from the flux overpopulation method and the
      sampling of events that lead to productive collisions even if their probability
      is extremely small (because of large free-energy barriers that separate them from
      the higher probability events). Using these developments, we demonstrate that a
      coarse-grained model of the four-helix bundle can be simulated in several days on
      current supercomputers. Furthermore, such simulations yield folding times that
      are in the range of time scales observed in experiments.

PMID- 9539730
TI  - Chromophore-assisted light inactivation and self-organization of microtubules and
      motors.
AB  - Chromophore-assisted light inactivation (CALI) offers the only method capable of
      modulating specific protein activities in localized regions and at particular
      times. Here, we generalize CALI so that it can be applied to a wider range of
      tasks. Specifically, we show that CALI can work with a genetically inserted
      epitope tag; we investigate the effectiveness of alternative dyes, especially
      fluorescein, comparing them with the standard CALI dye, malachite green; and we
      study the relative efficiencies of pulsed and continuous-wave illumination. We
      then use fluorescein-labeled hemagglutinin antibody fragments, together with
      relatively low-power continuous-wave illumination to examine the effectiveness of
      CALI targeted to kinesin. We show that CALI can destroy kinesin activity in at
      least two ways: it can either result in the apparent loss of motor activity, or
      it can cause irreversible attachment of the kinesin enzyme to its microtubule
      substrate. Finally, we apply this implementation of CALI to an in vitro system of
      motor proteins and microtubules that is capable of self-organized aster
      formation. In this system, CALI can effectively perturb local structure formation
      by blocking or reducing the degree of aster formation in chosen regions of the
      sample, without influencing structure formation elsewhere.

PMID- 9539731
TI  - Definition of amide protection factors for early kinetic intermediates in protein
      folding.
AB  - Hydrogen-deuterium exchange experiments have been used previously to investigate
      the structures of well defined states of a given protein. These include the
      native state, the unfolded state, and any intermediates that can be stably
      populated at equilibrium. More recently, the hydrogen-deuterium exchange
      technique has been applied in kinetic labeling experiments to probe the
      structures of transiently formed intermediates on the kinetic folding pathway of
      a given protein. From these equilibrium and nonequilibrium studies, protection
      factors are usually obtained. These protection factors are defined as the ratio
      of the rate of exchange of a given backbone amide when it is in a fully solvent
      exposed state (usually obtained from model peptides) to the rate of exchange of
      that amide in some state of the protein or in some intermediate on the folding
      pathway of the protein. This definition is straightforward for the case of
      equilibrium studies; however, it is less clear-cut for the case of transient
      kinetic intermediates. To clarify the concept for the case of burst-phase
      intermediates, we have introduced and mathematically defined two different types
      of protection factors: one is P struc, which is more related to the structure of
      the intermediate, and the other is P app, which is more related to the stability
      of the intermediate. Kinetic hydrogen-deuterium exchange data from disulfide
      intact ribonuclease A and from cytochrome c are discussed to explain the use and
      implications of these two definitions.

PMID- 9539732
TI  - Sequence-specific polypeptoids: a diverse family of heteropolymers with stable
      secondary structure.
AB  - We have synthesized and characterized a family of structured oligo-N-substituted
      glycines (peptoids) up to 36 residues in length by using an efficient solid-phase
      protocol to incorporate chemically diverse side chains in a sequence-specific
      fashion. We investigated polypeptoids containing side chains with a chiral center
      adjacent to the main chain nitrogen. Some of these sequences have stable
      secondary structure, despite the achirality of the polymer backbone and its lack
      of hydrogen bond donors. In both aqueous and organic solvents, peptoid oligomers
      as short as five residues give rise to CD spectra that strongly resemble those of
      peptide alpha-helices. Differential scanning calorimetry and CD measurements show
      that polypeptoid secondary structure is highly stable and that unfolding is
      reversible and cooperative. Thermodynamic parameters obtained for unfolding are
      similar to those obtained for the alpha-helix to coil transitions of peptides.
      This class of biomimetic polymers may enable the design of self-assembling
      macromolecules with novel structures and functions.

PMID- 9539733
TI  - NMR determination of the major solution conformation of a peptoid pentamer with
      chiral side chains.
AB  - Polymers of N-substituted glycines ("peptoids") containing chiral centers at the
      alpha position of their side chains can form stable structures in solution. We
      studied a prototypical peptoid, consisting of five para-substituted (S)-N-(1
      phenylethyl)glycine residues, by NMR spectroscopy. Multiple configurational
      isomers were observed, but because of extensive signal overlap, only the major
      isomer containing all cis-amide bonds was examined in detail. The NMR data for
      this molecule, in conjunction with previous CD spectroscopic results, indicate
      that the major species in methanol is a right-handed helix with cis-amide bonds.
      The periodicity of the helix is three residues per turn, with a pitch of
      approximately 6 A. This conformation is similar to that anticipated by
      computational studies of a chiral peptoid octamer. The helical repeat orients the
      amide bond chromophores in a manner consistent with the intensity of the CD
      signal exhibited by this molecule. Many other chiral polypeptoids have similar CD
      spectra, suggesting that a whole family of peptoids containing chiral side chains
      is capable of adopting this secondary structure motif. Taken together, our
      experimental and theoretical studies of the structural properties of chiral
      peptoids lay the groundwork for the rational design of more complex polypeptoid
      molecules, with a variety of applications, ranging from nanostructures to
      nonviral gene delivery systems.

PMID- 9539734
TI  - The theoretical limits of DNA sequence discrimination by linked polyamides.
AB  - Linked polyamides bind in the minor groove of double-stranded DNA in a partially
      sequence-specific manner. This report analyzes the theoretical limits of DNA
      sequence discrimination by linked polyamides composed of two to four different
      types of heterocyclic rings, determining (i) the optimal choice of base-binding
      specificity for each ring and (ii) the optimal design for a polyamide composed of
      these rings to target a given DNA sequence and designed to maximize the fraction
      of the total polyamide binding to the specified target sequence relative to all
      other sequences. The results show that, fortuitously, polyamides composed of
      pyrrole, a naturally occurring G-excluding element, and imidazole, a rationally
      designed G-favoring element, have features similar to the theoretical optimum
      design for polyamides composed of two different rings. The results also show
      that, in polyamides composed of two or three types of heterocyclic rings,
      choosing a nonspecific "placeholder" ring, which binds equally strongly to each
      of the four bases, along with one or two base-specific rings will often enhance
      sequence specificity over a polyamide composed entirely of base-specific rings.

PMID- 9539735
TI  - Translocation of inserted foreign epitopes by a channel-forming protein.
AB  - Certain bacterial protein toxins are able to insert themselves into, and at least
      partially across, lipid bilayer membranes in the absence of any auxiliary
      proteins, by using unknown mechanisms to overcome the high energy barrier
      presented by the hydrophobic bilayer core. We have previously shown that one such
      toxin, colicin Ia, translocates a large, hydrophilic part of itself completely
      across a lipid bilayer in conjunction with the formation of an ion-conducting
      channel. To address the question of whether the colicin can translocate any
      arbitrary amino acid sequence, we have altered the translocated segment by
      inserting, singly, two different foreign epitopes. Colicins containing either
      epitope retain significant bactericidal activity and form channels of normal
      conductance in planar bilayers. Furthermore, antibodies added on the side of the
      bilayer opposite that to which the colicin was added interact specifically with
      the corresponding epitopes, producing an inhibition of channel closing. Thus, the
      inserted epitopes are translocated along with the rest of the segment, suggesting
      that a surprisingly small part of colicin Ia, located elsewhere in the molecule,
      acts as a nonspecific protein translocator.

PMID- 9539736
TI  - Simultaneous determination of helical unwinding angles and intrinsic association
      constants in ligand-DNA complexes: the interaction between DNA and
      calichearubicin B.
AB  - We present a helical unwinding assay for reversibly binding DNA ligands that uses
      closed circular DNA, topoisomerase I (Topo I), and two-dimensional agarose gel
      electrophoresis. Serially diluted Topo I relaxation reactions at constant
      DNA/ligand ratio are performed, and the resulting apparent unwinding of the
      closed circular DNA is used to calculate both ligand unwinding angle (phi) and
      intrinsic association constant (Ka). Mathematical treatment of apparent unwinding
      is formally analogous to that of apparent extinction coefficient data for optical
      binding titrations. Extrapolation to infinite DNA concentration yields the true
      unwinding angle of a given ligand and its association constant under Topo I
      relaxation conditions. Thus this assay delivers simultaneous structural and
      thermodynamic information describing the ligand-DNA complex. The utility of this
      assay has been demonstrated by using calichearubicin B (CRB), a synthetic hybrid
      molecule containing the anthraquinone chromophore of (DA) and the carbohydrate
      domain of calicheamicin gamma1I. The unwinding angle for CRB calculated by this
      method is -5. 3 +/- 0.5 degrees. Its Ka value is 0.20 x 10(6) M-1. For
      comparison, the unwinding angles of ethidium bromide and DA have been
      independently calculated, and the results are in agreement with canonical values
      for these compounds. Although a stronger binder to selected sites, CRB is a less
      potent unwinder than its parent compound DA. The assay requires only small
      amounts of ligand and offers an attractive option for analysis of DNA binding by
      synthetic and natural compounds.

PMID- 9539737
TI  - ADD1/SREBP1 activates PPARgamma through the production of endogenous ligand.
AB  - Adipose differentiation is an important part of the energy homeostasis system of
      higher organisms. Recent data have suggested that this process is controlled by
      an interplay of transcription factors including PPARgamma, the C/EBPs, and
      ADD1/SREBP1. Although these factors interact functionally to initiate the program
      of differentiation, there are no data concerning specific mechanisms of
      interaction. We show here that the expression of ADD1/SREBP1 specifically
      increases the activity of PPARgamma but not other isoforms, PPARalpha, or
      PPARdelta. This activation occurs through the ligand-binding domain of PPARgamma
      when it is fused to the DNA-binding domain of Gal4. The stimulation of PPARgamma
      by ADD1/SREBP1 does not require coexpression in the same cells; supernatants from
      cultures that express ADD1/SREBP1 augment the transcriptional activity of
      PPARgamma. Finally, we demonstrate directly that cells expressing ADD1/SREBP1
      produce and secrete lipid molecule(s) that bind directly to PPARgamma, displacing
      the binding of radioactive thiazolidinedione ligands. These data establish that
      ADD1/SREBP1 can control the production of endogenous ligand(s) for PPARgamma and
      suggest a mechanism for coordinating the actions of these adipogenic factors.

PMID- 9539738
TI  - Segregation of viral plasmids depends on tethering to chromosomes and is
      regulated by phosphorylation.
AB  - Eukaryotic viruses can maintain latency in dividing cells as extrachromosomal
      nuclear plasmids. Segregation and nuclear retention of DNA is, therefore, a key
      issue in retaining copy number. The E2 enhancer protein of the papillomaviruses
      is required for viral DNA replication and transcription. Viral mutants that
      prevent phosphorylation of the bovine papillomavirus type 1 (BPV) E2 protein are
      transformation-defective, despite normal viral gene expression and replication
      function. Cell colonies harboring such mutants show sectoring of viral DNA and
      are unable to maintain the episome. We find that transforming viral DNA attaches
      to mitotic chromosomes, in contrast to the mutant genome encoding the E2
      phosphorylation mutant. Second-site suppressor mutations were uncovered in both
      E1 and E2 genes that allow for transformation, maintenance, and chromosomal
      attachment. E2 protein was also found to colocalize to mitotic chromosomes,
      whereas the mutant did not, suggesting a direct role for E2 in viral attachment
      to chromosomes. Such viral hitch-hiking onto cellular chromosomes is likely to
      provide a general mechanism for maintaining nuclear plasmids.

PMID- 9539739
TI  - Cyclin B2-null mice develop normally and are fertile whereas cyclin B1-null mice
      die in utero.
AB  - Two B-type cyclins, B1 and B2, have been identified in mammals. Proliferating
      cells express both cyclins, which bind to and activate p34(cdc2). To test whether
      the two B-type cyclins have distinct roles, we generated lines of transgenic
      mice, one lacking cyclin B1 and the other lacking cyclin B2. Cyclin B1 proved to
      be an essential gene; no homozygous B1-null pups were born. In contrast,
      nullizygous B2 mice developed normally and did not display any obvious
      abnormalities. Both male and female cyclin B2-null mice were fertile, which was
      unexpected in view of the high levels and distinct patterns of expression of
      cyclin B2 during spermatogenesis. We show that the expression of cyclin B1
      overlaps the expression of cyclin B2 in the mature testis, but not vice versa.
      Cyclin B1 can be found both on intracellular membranes and free in the cytoplasm,
      in contrast to cyclin B2, which is membrane-associated. These observations
      suggest that cyclin B1 may compensate for the loss of cyclin B2 in the mutant
      mice, and implies that cyclin B1 is capable of targeting the p34(cdc2) kinase to
      the essential substrates of cyclin B2.

PMID- 9539740
TI  - Human PEX1 cloned by functional complementation on a CHO cell mutant is
      responsible for peroxisome-deficient Zellweger syndrome of complementation group
      I.
AB  - The peroxisome biogenesis disorders (PBDs), including Zellweger syndrome (ZS) and
      neonatal adrenoleukodystrophy (NALD), are autosomal recessive diseases caused by
      defects in peroxisome assembly, for which at least 10 complementation groups have
      been reported. We have isolated a human PEX1 cDNA (HsPEX1) by functional
      complementation of peroxisome deficiency of a mutant Chinese hamster ovary (CHO)
      cell line, ZP107, transformed with peroxisome targeting signal type 1-tagged
      "enhanced" green fluorescent protein. This cDNA encodes a hydrophilic protein
      (Pex1p) comprising 1,283 amino acids, with high homology to the AAA-type ATPase
      family. A stable transformant of ZP107 with HsPEX1 was morphologically and
      biochemically restored for peroxisome biogenesis. HsPEX1 expression restored
      peroxisomal protein import in fibroblasts from three patients with ZS and NALD of
      complementation group I (CG-I), which is the highest-incidence PBD. A CG-I ZS
      patient (PBDE-04) possessed compound heterozygous, inactivating mutations: a
      missense point mutation resulting in Leu-664 --> Pro and a deletion of the
      sequence from Gly-634 to His-690 presumably caused by missplicing (splice site
      mutation). Both PBDE-04 PEX1 cDNAs were defective in peroxisome-restoring
      activity when expressed in the patient fibroblasts as well as in ZP107 cells.
      These results demonstrate that PEX1 is the causative gene for CG-I peroxisomal
      disorders.

PMID- 9539741
TI  - Evidence for keratinocyte stem cells in vitro: long term engraftment and
      persistence of transgene expression from retrovirus-transduced keratinocytes.
AB  - Epidermis is renewed by a population of stem cells that have been defined in vivo
      by slow turnover, label retention, position in the epidermis, and enrichment in
      beta1 integrin, and in vitro by clonogenic growth, prolonged serial passage, and
      rapid adherence to extracellular matrix. The goal of this study is to determine
      whether clonogenic cells with long-term growth potential in vitro persist in vivo
      and give rise to a fully differentiated epidermis. Human keratinocytes were
      genetically labeled in culture by transduction with a retrovirus encoding the
      lacZ gene and grafted to athymic mice. Analysis of the cultures before grafting
      showed that 21.1-27.8% of clonogenic cells with the capacity for >30 generations
      were successfully transduced. In vivo, beta-galactosidase (beta-gal) positive
      cells participated in the formation of a fully differentiated epithelium and were
      detected throughout the 40-week postgraft period, initially as loosely scattered
      clusters and later as distinct vertical columns. Viable cells recovered from
      excised grafts were seeded at clonal densities and 23.3-33.3% of the colonies
      thus formed were beta-gal positive. In addition, no evidence of transgene
      inactivation was obtained: all keratinocyte colonies recovered from grafted
      tissue that were beta-gal negative also lacked the lacZ transgene. These results
      show that cells with long-term growth properties in vitro do indeed persist in
      vivo and form a fully differentiated epidermis, thereby exhibiting the properties
      of stem cells.

PMID- 9539742
TI  - Dynamics of contacts between lamellae of fibroblasts: essential role of the actin
      cytoskeleton.
AB  - We investigated actin cytoskeletal and adhesion molecule dynamics during
      collisions of leading lamellae of nontransformed and oncogene-transformed
      fibroblasts. By using real-time video microscopy, it was found that during
      lamellar collision there was considerable overlapping of leading lamellae
      followed by subsequent retraction. Overlapping of nontransformed fibroblasts was
      accompanied by formation of beta-catenin-positive contact structures organized
      into strands oriented parallel to the long axis of the cell that were associated
      with bundles of actin filaments. Maintenance of such cell-cell contact structures
      critically depended on the contractility of actin cytoskeleton, as inhibition of
      contractility with serum-free medium or 2,3-butanedione 2-monoxime (BDM) resulted
      in loss of strand formation. Strand formation was recovered when cells in serum
      free medium were incubated with the microtubule inhibitor nocodazole, which is
      known to increase contractility. Oncogene-transformed fibroblasts reacted to
      collisions with responses similar to nontransformed fibroblasts but did not
      develop well-organized cell-cell contacts. A model is presented to describe how
      differences in the organization of the actin cytoskeleton could account for the
      structurally distinct responses to cell-cell contact by polarized fibroblastic
      cells versus nonpolarized epithelial cells.

PMID- 9539743
TI  - Plant nuclear gene knockout reveals a role in plastid division for the homolog of
      the bacterial cell division protein FtsZ, an ancestral tubulin.
AB  - Little is known about the division of eukaryotic cell organelles and up to now
      neither in animals nor in plants has a gene product been shown to mediate this
      process. A cDNA encoding a homolog of the bacterial cell division protein FtsZ,
      an ancestral tubulin, was isolated from the eukaryote Physcomitrella patens and
      used to disrupt efficiently the genomic locus in this terrestrial seedless plant.
      Seven out of 51 transgenics obtained were knockout plants generated by homologous
      recombination; they were specifically impeded in plastid division with no
      detectable effect on mitochondrial division or plant morphology. Implications on
      the theory of endosymbiosis and on the use of reverse genetics in plants are
      discussed.

PMID- 9539744
TI  - Cell adhesion and the integrin-linked kinase regulate the LEF-1 and beta-catenin
      signaling pathways.
AB  - The integrin-linked kinase (ILK) is an ankyrin repeat containing serine-threonine
      protein kinase that can interact directly with the cytoplasmic domains of the
      beta1 and beta3 integrin subunits and whose kinase activity is modulated by cell
      extracellular matrix interactions. Overexpression of constitutively active ILK
      results in loss of cell-cell adhesion, anchorage-independent growth, and
      tumorigenicity in nude mice. We now show that modest overexpression of ILK in
      intestinal epithelial cells as well as in mammary epithelial cells results in an
      invasive phenotype concomitant with a down-regulation of E-cadherin expression,
      translocation of beta-catenin to the nucleus, formation of a complex between beta
      catenin and the high mobility group transcription factor, LEF-1, and
      transcriptional activation by this LEF-1/beta-catenin complex. We also find that
      LEF-1 protein expression is rapidly modulated by cell detachment from the
      extracellular matrix, and that LEF-1 protein levels are constitutively up
      regulated at ILK overexpression. These effects are specific for ILK, because
      transformation by activated H-ras or v-src oncogenes do not result in the
      activation of LEF-1/beta-catenin. The results demonstrate that the oncogenic
      properties of ILK involve activation of the LEF-1/beta-catenin signaling pathway,
      and also suggest ILK-mediated cross-talk between cell-matrix interactions and
      cell-cell adhesion as well as components of the Wnt signaling pathway.

PMID- 9539745
TI  - Translation of cytochrome f is autoregulated through the 5' untranslated region
      of petA mRNA in Chlamydomonas chloroplasts.
AB  - A process that we refer to as control by epistasy of synthesis (CES process)
      occurs during chloroplast protein biogenesis in Chlamydomonas reinhardtii: the
      synthesis of some chloroplast-encoded subunits, the CES subunits, is strongly
      attenuated when some other subunits from the same complex, the dominant subunits,
      are missing. Herein we investigate the molecular basis of the CES process for the
      biogenesis of the cytochrome b6f complex and show that negative autoregulation of
      cytochrome f translation occurs in the absence of other complex subunits. This
      autoregulation is mediated by an interaction, either direct or indirect, between
      the 5' untranslated region of petA mRNA, which encodes cytochrome f, and the C
      terminal domain of the unassembled protein. This model for the regulation of
      cytochrome f translation explains both the decreased rate of cytochrome f
      synthesis in vivo in the absence of its assembly partners and its increase in
      synthesis when significant accumulation of the C-terminal domain of the protein
      is prevented. When expressed from a chimeric mRNA containing the atpA 5'
      untranslated region, cytochrome f no longer showed an assembly-dependent
      regulation of translation. Conversely, the level of antibiotic resistance
      conferred by a chimeric petA-aadA-rbcL gene was shown to depend on the state of
      assembly of cytochrome b6f complexes and on the accumulation of the C-terminal
      domain of cytochrome f. We discuss the possible ubiquity of the CES process in
      organellar protein biogenesis.

PMID- 9539746
TI  - Bcl-XL interacts with Apaf-1 and inhibits Apaf-1-dependent caspase-9 activation.
AB  - Recent studies indicate that Caenorhabditis elegans CED-4 interacts with and
      promotes the activation of the death protease CED-3, and that this activation is
      inhibited by CED-9. Here we show that a mammalian homolog of CED-4, Apaf-1, can
      associate with several death proteases, including caspase-4, caspase-8, caspase
      9, and nematode CED-3 in mammalian cells. The interaction with caspase-9 was
      mediated by the N-terminal CED-4-like domain of Apaf-1. Expression of Apaf-1
      enhanced the killing activity of caspase-9 that required the CED-4-like domain of
      Apaf-1. Furthermore, Apaf-1 promoted the processing and activation of caspase-9
      in vivo. Bcl-XL, an antiapoptotic member of the Bcl-2 family, was shown to
      physically interact with Apaf-1 and caspase-9 in mammalian cells. The association
      of Apaf-1 with Bcl-XL was mediated through both its CED-4-like domain and the C
      terminal domain containing WD-40 repeats. Expression of Bcl-XL inhibited the
      association of Apaf-1 with caspase-9 in mammalian cells. Significantly,
      recombinant Bcl-XL purified from Escherichia coli or insect cells inhibited Apaf
      1-dependent processing of caspase-9. Furthermore, Bcl-XL failed to inhibit
      caspase-9 processing mediated by a constitutively active Apaf-1 mutant,
      suggesting that Bcl-XL regulates caspase-9 through Apaf-1. These experiments
      demonstrate that Bcl-XL associates with caspase-9 and Apaf-1, and show that Bcl
      XL inhibits the maturation of caspase-9 mediated by Apaf-1, a process that is
      evolutionarily conserved from nematodes to humans.

PMID- 9539747
TI  - Essential role of germinal vesicle material in the meiotic cell cycle of Xenopus
      oocytes.
AB  - In almost all animal species, immature oocytes are arrested naturally in the
      first meiotic prophase, with a large nucleus called the germinal vesicle. A
      number of previous studies showed that both activation of maturation/M phase
      promoting factor (MPF) (assayed by semiquantitative cytological methods) and some
      other maturational events occur essentially normally in enucleated oocytes from
      many amphibian species and mice. Hence, for nearly three decades, it has
      generally been believed that nuclear material is dispensable for MPF activation
      and the meiotic cell cycle in vertebrate oocytes. Here, we have challenged this
      view by examining the histone H1 kinase activities and the molecular forms of MPF
      in experimentally manipulated Xenopus oocytes. We show that oocytes injected with
      nuclear material undergo much more rapid MPF activation and maturation than
      uninjected control oocytes. Conversely, enucleated oocytes, unlike nucleated
      counterparts, undergo only weak MPF activation in meiosis I and no detectable MPF
      reactivation in meiosis II, the latter accompanying inhibitory tyrosine
      phosphorylation of cdc2 kinase, the catalytic subunit of MPF. These results argue
      strongly that nuclear material is indispensable for the meiotic cell cycle,
      particularly MPF reactivation (or cdc2 tyrosine dephosphorylation) on entry into
      meiosis II, in Xenopus oocytes. The classical and general view may thus need
      reconsideration.

PMID- 9539748
TI  - Cooperation between the activin and Wnt pathways in the spatial control of
      organizer gene expression.
AB  - The normal expression pattern of the Wnt responsive homeobox gene Siamois is
      restricted to the dorso-vegetal region of the Xenopus embryo. Because the Wnt
      signaling pathway (via beta-catenin) is active on the entire dorsal side of the
      early embryo, we have asked why Siamois expression is not seen in the dorsal
      ectoderm. Only Wnt signaling, via activation of beta-catenin, can induce directly
      Siamois, and signaling via the SMAD1 (BMP2/4) or SMAD2 (activin/Vg-1) pathways
      cannot. We now directly show that the SMAD2 pathway can cooperate with the Wnt
      pathway to induce expression of Siamois much more strongly than the Wnt pathway
      alone, in normal embryos. We demonstrate the significance of this cooperation in
      normal embryos by blocking the SMAD2 signaling pathway with a dominant negative
      activin receptor. The activin dominant negative receptor blocks this cooperative
      effect and reduces the expression of Siamois by threefold in early embryos.
      Furthermore, we find that this cooperative relationship between the SMAD2 and Wnt
      pathways is reciprocal. Thus, in normal embryos, the Wnt pathway can enhance
      induction, by the SMAD 2 pathway, of the organizer genes Gsc and Chd but not the
      pan-mesodermal marker genes Xbra and Eomes. We conclude that the Wnt and SMAD2
      signaling pathways cooperate to induce the expression of Spemann-organizer
      specific genes and so help to localize their spatial expression.

PMID- 9539749
TI  - The identification of a 9-cis retinol dehydrogenase in the mouse embryo reveals a
      pathway for synthesis of 9-cis retinoic acid.
AB  - The ligand-controlled retinoic acid (RA) receptors and retinoid X receptors are
      important for several physiological processes, including normal embryonic
      development, but little is known about how their ligands, all-trans and 9-cis RA,
      are generated. Here we report the identification of a stereo-specific 9-cis
      retinol dehydrogenase, which is abundantly expressed in embryonic tissues known
      to be targets in the retinoid signaling pathway. The membrane-bound enzyme is a
      member of the short-chain alcohol dehydrogenase/reductase superfamily, able to
      oxidize 9-cis retinol into 9-cis retinaldehyde, an intermediate in 9-cis RA
      biosynthesis. Analysis by nonradioactive in situ hybridization in mouse embryos
      shows that expression of the enzyme is temporally and spatially well controlled
      during embryogenesis with prominent expression in parts of the developing central
      nervous system, sensory organs, somites and myotomes, and several tissues of
      endodermal origin. The identification of this enzyme reveals a pathway in RA
      biosynthesis, where 9-cis retinol is generated for subsequent oxidation to 9-cis
      RA.

PMID- 9539750
TI  - When defense backfires: detrimental effect of a plant's protective trichomes on
      an insect beneficial to the plant.
AB  - The plant Mentzelia pumila (family Loasaceae) has leaves and stems densely
      covered with tiny hooked trichomes. The structures entrap and kill insects and
      therefore are most probably protective. But they are also maladaptive in that
      they incapacitate a coccinellid beetle (Hippodamia convergens) that preys upon an
      aphid enemy (Macrosiphum mentzeliae) of the plant. The adaptive benefit provided
      by the trichomes is evidently offset by a cost.

PMID- 9539751
TI  - The location of Z- and W-linked marker genes and sequence on the homomorphic sex
      chromosomes of the ostrich and the emu.
AB  - Perhaps the most striking fact about early Cenozoic avian history some 70 million
      years ago was the rapid radiation of large, flightless, ground-living birds. It
      has been suggested that, for a time, there was active competition between these
      large terrestrial birds and the early mammals. Probably reflecting the above
      noted early start of Ratitae of the infraclass Eoaves, the presumptive sex
      chromosomes of their present day survivors, such as the emu and the ostrich,
      largely remained homomorphic. The signs of genetic differentiation between their
      still-homomorphic Z and W chromosomes were tested by using two marker genes (Z
      linked ZOV3 and the gene for the iron-responsive element-binding protein) and one
      marker sequence of a part of a presumptive pseudogene (W-linked EE0.6 of the
      chicken). Their homologues, maintaining 71-92% identities to the chicken
      counterparts, were found in both the emu (Dromaius novaehollandiae) and the
      ostrich (Struthio camelus). Their locations were visualized on chromosome
      preparations by fluorescence in situ hybridization. In the case of the emu, these
      three marker sequences were localized on both members of the fifth pair of a
      female, thus revealing no sign yet of genetic differentiation between the Z and
      the W. The finding was the same with regard to both members of the fourth pair of
      male ostriches. In the female ostrich, however, the sequence of the gene for the
      iron-responsive element-binding protein was missing from one of the pairs, thus
      revealing the differentiation by a small deletion of the W from the Z.

PMID- 9539752
TI  - Polyploid formation created unique avenues for response to selection in Gossypium
      (cotton).
AB  - A detailed restriction fragment length polymorphism map was used to determine the
      chromosomal locations and subgenomic distributions of quantitative trait loci
      (QTLs) segregating in a cross between cultivars of allotetraploid (AADD)
      Gossypium hirsutum ("Upland" cotton) and Gossypium barbadense ("Sea Island,"
      "Pima," or "Egyptian" cotton) that differ markedly in the quality and quantity of
      seed epidermal fibers. Most QTLs influencing fiber quality and yield are located
      on the "D" subgenome, derived from an ancestor that does not produce spinnable
      fibers. D subgenome QTLs may partly account for the fact that domestication and
      breeding of tetraploid cottons has resulted in fiber yield and quality levels
      superior to those achieved by parallel improvement of "A" genome diploid cottons.
      The merger of two genomes with different evolutionary histories in a common
      nucleus appears to offer unique avenues for phenotypic response to selection.
      This may partly compensate for reduction in quantitative variation associated
      with polyploid formation and be one basis for the prominence of polyploids among
      extant angiosperms. These findings impel molecular dissection of the roles of
      divergent subgenomes in quantitative inheritance in many other polyploids and
      further exploration of both "synthetic" polyploids and exotic diploid genotypes
      for agriculturally useful variation.

PMID- 9539753
TI  - Malaria's Eve: evidence of a recent population bottleneck throughout the world
      populations of Plasmodium falciparum.
AB  - We have analyzed DNA sequences from world-wide geographic strains of Plasmodium
      falciparum and found a complete absence of synonymous DNA polymorphism at 10 gene
      loci. We hypothesize that all extant world populations of the parasite have
      recently derived (within several thousand years) from a single ancestral strain.
      The upper limit of the 95% confidence interval for the time when this most recent
      common ancestor lived is between 24,500 and 57,500 years ago (depending on
      different estimates of the nucleotide substitution rate); the actual time is
      likely to be much more recent. The recent origin of the P. falciparum populations
      could have resulted from either a demographic sweep (P. falciparum has only
      recently spread throughout the world from a small geographically confined
      population) or a selective sweep (one strain favored by natural selection has
      recently replaced all others). The selective sweep hypothesis requires that
      populations of P. falciparum be effectively clonal, despite the obligate sexual
      stage of the parasite life cycle. A demographic sweep that started several
      thousand years ago is consistent with worldwide climatic changes ensuing the last
      glaciation, increased anthropophilia of the mosquito vectors, and the spread of
      agriculture. P. falciparum may have rapidly spread from its African tropical
      origins to the tropical and subtropical regions of the world only within the last
      6,000 years. The recent origin of the world-wide P. falciparum populations may
      account for its virulence, as the most malignant of human malarial parasites.

PMID- 9539754
TI  - Female preference for swords in Xiphophorus helleri reflects a bias for large
      apparent size.
AB  - Swordtail fish (Poeciliidae: genus Xiphophorus) are a paradigmatic case of sexual
      selection by sensory exploitation. Female preference for males with a conspicuous
      "sword" ornament is ancestral, suggesting that male morphology has evolved in
      response to a preexisting bias. The perceptual mechanisms underlying female mate
      choice have not been identified, complicating efforts to understand the selection
      pressures acting on ornament design. We consider two alternative models of
      receiver behavior, each consistent with previous results. Females could respond
      either to specific characteristics of the sword or to more general cues, such as
      the apparent size of potential mates. We showed female swordtails a series of
      computer-altered video sequences depicting a courting male. Footage of an intact
      male was preferred strongly to otherwise identical sequences in which portions of
      the sword had been deleted selectively, but a disembodied courting sword was less
      attractive than an intact male. There was no difference between responses to an
      isolated sword and to a swordless male of comparable length, or between an
      isolated sword and a homogenous background. Female preference for a sworded male
      was abolished by enlarging the image of a swordless male to compensate for the
      reduction in length caused by removing the ornament. This pattern of results is
      consistent with mate choice being mediated by a general preference for large
      males rather than by specific characters. Similar processes may account for the
      evolution of exaggerated traits in other systems.

PMID- 9539755
TI  - Gene number in an invertebrate chordate, Ciona intestinalis.
AB  - Gene number can be considered a pragmatic measure of biological complexity, but
      reliable data is scarce. Estimates for vertebrates are 50-100,000 genes per
      haploid genome, whereas invertebrate estimates fall below 25,000. We wished to
      test the hypothesis that the origin of vertebrates coincided with extensive gene
      creation. A prediction is that gene number will differ sharply between
      invertebrate and vertebrate members of the chordate phylum. A gene number
      estimation method requiring limited sequence sampling of genomic DNA was
      developed and validated by using data for Caenorhabditis elegans. Using the
      method, we estimated that the invertebrate chordate Ciona intestinalis has 15,500
      protein-coding genes (+/-3,700). This number is significantly lower than gene
      numbers of vertebrate chordates, but similar to those of invertebrates in
      distantly related phyla. The data indicate that evolution of vertebrates was
      accompanied by a dramatic increase in protein-coding capacity of the genome.

PMID- 9539756
TI  - Investigation of the bottleneck leading to the domestication of maize.
AB  - Maize (Zea mays ssp. mays) is genetically diverse, yet it is also morphologically
      distinct from its wild relatives. These two observations are somewhat
      contradictory: the first observation is consistent with a large historical
      population size for maize, but the latter observation is consistent with strong,
      diversity-limiting selection during maize domestication. In this study, we
      sampled sequence diversity, coupled with simulations of the coalescent process,
      to study the dynamics of a population bottleneck during the domestication of
      maize. To do this, we determined the DNA sequence of a 1,400-bp region of the
      Adh1 locus from 19 individuals representing maize, its presumed progenitor (Z.
      mays ssp. parviglumis), and a more distant relative (Zea luxurians). The sequence
      data were used to guide coalescent simulations of population bottlenecks
      associated with domestication. Our study confirms high genetic diversity in maize
      maize contains 75% of the variation found in its progenitor and is more diverse
      than its wild relative, Z. luxurians-but it also suggests that sequence diversity
      in maize can be explained by a bottleneck of short duration and very small size.
      For example, the breadth of genetic diversity in maize is consistent with a
      founding population of only 20 individuals when the domestication event is 10
      generations in length.

PMID- 9539757
TI  - Extent of genomic rearrangement after genome duplication in yeast.
AB  - Whole-genome duplication approximately 10(8) years ago was proposed as an
      explanation for the many duplicated chromosomal regions in Saccharomyces
      cerevisiae. Here we have used computer simulations and analytic methods to
      estimate some parameters describing the evolution of the yeast genome after this
      duplication event. Computer simulation of a model in which 8% of the original
      genes were retained in duplicate after genome duplication, and 70-100 reciprocal
      translocations occurred between chromosomes, produced arrangements of duplicated
      chromosomal regions very similar to the map of real duplications in yeast. An
      analytical method produced an independent estimate of 84 map disruptions. These
      results imply that many smaller duplicated chromosomal regions exist in the yeast
      genome in addition to the 55 originally reported. We also examined the
      possibility of determining the original order of chromosomal blocks in the
      ancestral unduplicated genome, but this cannot be done without information from
      one or more additional species. If the genome sequence of one other species (such
      as Kluyveromyces lactis) were known it should be possible to identify 150-200
      paired regions covering the whole yeast genome and to reconstruct approximately
      two-thirds of the original order of blocks of genes in yeast. Rates of
      interchromosome translocation in yeast and mammals appear similar despite their
      very different rates of homologous recombination per kilobase.

PMID- 9539758
TI  - Instability of signaling resolution models of parent-offspring conflict.
AB  - Recent signaling resolution models of parent-offspring conflict have provided an
      important framework for theoretical and empirical studies of communication and
      parental care. According to these models, signaling of need is stabilized by its
      cost. However, our computer simulations of the evolutionary dynamics of chick
      begging and parental investment show that in Godfray's model the signaling
      equilibrium is evolutionarily unstable: populations that start at the signaling
      equilibrium quickly depart from it. Furthermore, the signaling and nonsignaling
      equilibria are linked by a continuum of equilibria where chicks above a certain
      condition do not signal and we show that, contrary to intuition, fitness
      increases monotonically as the proportion of young that signal decreases. This
      result forces us to reconsider much of the current literature on signaling of
      need and highlights the need to investigate the evolutionary stability of
      signaling equilibria based on the handicap principle.

PMID- 9539759
TI  - Deleterious mutations destabilize ribosomal RNA in endosymbiotic bacteria.
AB  - In populations that are small and asexual, mutations with slight negative effects
      on fitness will drift to fixation more often than in large or sexual populations
      in which they will be eliminated by selection. If such mutations occur in
      substantial numbers, the combined effects of long-term asexuality and small
      population size may result in substantial accumulation of mildly deleterious
      substitutions. Prokaryotic endosymbionts of animals that are transmitted
      maternally for very long periods are effectively asexual and experience smaller
      effective population size than their free-living relatives. The contrast between
      such endosymbionts and related free-living bacteria allows us to test whether a
      population structure imposing frequent bottlenecks and asexuality does lead to an
      accumulation of slightly deleterious substitutions. Here we show that several
      independently derived insect endosymbionts, each with a long history of maternal
      transmission, have accumulated destabilizing base substitutions in the highly
      conserved 16S rRNA. Stabilities of Domain I of this subunit are 15-25% lower in
      endosymbionts than in closely related free-living bacteria. By mapping
      destabilizing substitutions onto a reconstructed phylogeny, we show that
      decreased ribosomal stability has evolved separately in each endosymbiont
      lineage. Our phylogenetic approach allows us to demonstrate statistical
      significance for this pattern: becoming endosymbiotic predictably results in
      decreased stability of rRNA secondary structure.

PMID- 9539760
TI  - The lethal mutation of the mouse wasted (wst) is a deletion that abolishes
      expression of a tissue-specific isoform of translation elongation factor 1alpha,
      encoded by the Eef1a2 gene.
AB  - We have identified the mutation responsible for the autosomal recessive wasted
      (wst) mutation of the mouse. Wasted mice are characterized by wasting and
      neurological and immunological abnormalities starting at 21 days after birth;
      they die by 28 days. A deletion of 15.8 kb in wasted mice abolishes expression of
      a gene called Eef1a2, encoding a protein that is 92% identical at the amino acid
      level to the translation elongation factor EF1alpha (locus Eef1a). We have found
      no evidence for the involvement of another gene in this deletion. Expression of
      Eef1a2 is reciprocal with that of Eef1a. Expression of Eef1a2 takes over from
      Eef1a in heart and muscle at precisely the time at which the wasted phenotype
      becomes manifest. These data suggest that there are tissue-specific forms of the
      translation elongation apparatus essential for postnatal survival in the mouse.

PMID- 9539761
TI  - Functional copies of a human gene can be directly isolated by transformation
      associated recombination cloning with a small 3' end target sequence.
AB  - Unique, small sequences (sequence tag sites) have been identified at the 3' ends
      of most human genes that serve as landmarks in genome mapping. We investigated
      whether a single copy gene could be isolated directly from total human DNA by
      transformation-associated recombination (TAR) cloning in yeast using a short, 3'
      unique target. A TAR cloning vector was constructed that, when linearized,
      contained a small amount (381 bp) of 3' hypoxanthine phosphoribosyltransferase
      (HPRT) sequence at one end and an 189-bp Alu repeat at the other end.
      Transformation with this vector along with human DNA led to selective isolations
      of the entire HPRT gene as yeast artificial chromosomes (YACs) that extended from
      the 3' end sequence to various Alu positions as much as 600 kb upstream. These
      YACs were retrofitted with a NeoR and a bacterial artificial chromosome (BAC)
      sequence to transfer the YACs to bacteria and subsequently the BACs to mouse
      cells by using a Neo selection. Most of the HPRT isolates were functional,
      demonstrating that TAR cloning retains the functional integrity of the isolated
      material. Thus, this modified version of TAR cloning, which we refer to as radial
      TAR cloning, can be used to isolate large segments of the human genome accurately
      and directly with only a small amount of sequence information.

PMID- 9539762
TI  - Molecular coevolution within a Drosophila clock gene.
AB  - The period (per) gene in Drosophila melanogaster provides an integral component
      of biological rhythmicity and encodes a protein that includes a repetitive
      threonine-glycine (Thr-Gly) tract. Similar repeats are found in the frq and wc2
      clock genes of Neurospora crassa and in the mammalian per homologues, but their
      circadian functions are unknown. In Drosophilids, the length of the Thr-Gly
      repeat varies widely between species, and sequence comparisons have suggested
      that the repeat length coevolves with the immediately flanking amino acids. A
      functional test of the coevolution hypothesis was performed by generating several
      hybrid per transgenes between Drosophila pseudoobscura and D. melanogaster, whose
      repetitive regions differ in length by about 150 amino acids. The positions of
      the chimeric junctions were slightly altered in each transgene. Transformants
      carrying per constructs in which the repeat of one species was juxtaposed next to
      the flanking region of the other were almost arrhythmic or showed a striking
      temperature sensitivity of the circadian period. In contrast, transgenes in which
      the repeat and flanking regions were conspecific gave wild-type levels of
      circadian rescue. These results support the coevolutionary interpretation of the
      interspecific sequence changes in this region of the PER molecule and reveal a
      functional dimension to this process related to the clock's temperature
      compensation.

PMID- 9539763
TI  - Impaired fetal T cell development and perinatal lethality in mice lacking the
      cAMP response element binding protein.
AB  - CREB, the cAMP response element binding protein, is a key transcriptional
      regulator of a large number of genes containing a CRE consensus sequence in their
      upstream regulatory regions. Mice with a hypomorphic allele of CREB that leads to
      a loss of the CREBalpha and delta isoforms and to an overexpression of the
      CREBbeta isoform are viable. Herein we report the generation of CREB null mice,
      which have all functional isoforms (CREBalpha, beta, and delta) inactivated. In
      contrast to the CREBalpha delta mice, CREB null mice are smaller than their
      littermates and die immediately after birth from respiratory distress. In brain,
      a strong reduction in the corpus callosum and the anterior commissures is
      observed. Furthermore, CREB null mice have an impaired fetal T cell development
      of the alpha beta lineage, which is not affected in CREBalpha delta mice on
      embryonic day 18.5. Overall thymic cellularity in CREB null mice is severely
      reduced affecting all developmental stages of the alpha beta T cell lineage. In
      contrast gamma delta T cell differentiation is normal in CREB mutant mice.

PMID- 9539764
TI  - Genetic analysis using genomic representations.
AB  - Analysis of the genetic changes in human tumors is often problematical because of
      the presence of normal stroma and the limited availability of pure tumor DNA.
      However, large amounts of highly reproducible "representations" of tumor and
      normal genomes can be made by PCR from nanogram amounts of restriction
      endonuclease cleaved DNA that has been ligated to oligonucleotide adaptors. We
      show here that representations are useful for many types of genetic analyses,
      including measuring relative gene copy number, loss of heterozygosity, and
      comparative genomic hybridization. Representations may be prepared even from
      sorted nuclei from fixed and archived tumor biopsies.

PMID- 9539765
TI  - Disruption of the CD4-major histocompatibility complex class II interaction
      blocks the development of CD4(+) T cells in vivo.
AB  - The experiments presented in this report were designed to specifically examine
      the role of CD4-major histocompatibility complex (MHC) class II interactions
      during T cell development in vivo. We have generated transgenic mice expressing
      class II molecules that cannot interact with CD4 but that are otherwise competent
      to present peptides to the T cell receptor. MHC class II expression was
      reconstituted in Abeta gene knock-out mice by injection of a transgenic construct
      encoding either the wild-type I-Abetab protein or a construct encoding a mutation
      designed to specifically disrupt binding to the CD4 molecule. We demonstrate that
      the mutation, EA137 and VA142 in the beta2 domain of I-Ab, is sufficient to
      disrupt CD4-MHC class II interactions in vivo. Furthermore, we show that this
      interaction is critical for the efficient selection of a complete repertoire of
      mature CD4(+) T helper cells as evidenced by drastically reduced numbers of
      conventional CD4(+) T cells in animals expressing the EA137/VA142 mutant I-Ab and
      by the failure to positively select the transgenic AND T cell receptor on the
      mutated I-Ab. These results underscore the importance of the CD4-class II
      interaction in the development of mature peripheral CD4(+) T cells.

PMID- 9539766
TI  - Unique molecular surface features of in vivo tolerized T cells.
AB  - Differential expression of surface markers can frequently be used to distinguish
      functional subsets of T cells, yet a surface phenotype unique to T cells induced
      into an anergic state has not been described. Here, we report that CD4 T cells
      rendered anergic in vivo by superantigen can be identified by loss of the 6C10 T
      cell marker. Inoculation of Vbeta8.1 T cell antigen receptor (TCR) transgenic
      mice with a Vbeta8.1-reactive minor lymphocyte-stimulating superantigen (Mls
      1(a)) induces tolerance to Mls-1(a) by clonal anergy. CD4 lymph node T cells from
      Mls-1(a) inoculated transgenic mice enriched for the 6C10(-) phenotype neither
      proliferate nor produce interleukin-2 upon TCR engagement, whereas 6C10(+) CD4 T
      cells retain responsiveness. Analysis of T cell memory markers demonstrate that
      6C10(-) T cells remain 3G11(hi) but express heterogeneous levels of CD45RB,
      CD62L, CD44, and the CD69 early activation marker, suggesting that T cells at
      various degrees of activation can be functionally anergic. These studies
      demonstrate that anergic T cells can be purified based on 6C10 expression
      permitting examination of issues concerning biochemical and biological features
      specific to T cell anergy.

PMID- 9539767
TI  - Immune regulation by the ST6Gal sialyltransferase.
AB  - The ST6Gal sialyltransferase controls production of the Siaalpha2-6Galbeta1
      4GlcNAc (Sia6LacNAc) trisaccharide, which is the ligand for the lectin CD22.
      Binding of CD22 to Sia6LacNAc is implicated in regulating lymphocyte adhesion and
      activation. We have investigated mice that lack ST6Gal and report that they are
      viable, yet exhibit hallmarks of severe immunosuppression unlike CD22-deficient
      mice. Notably, Sia6LacNAc-deficient mice display reduced serum IgM levels,
      impaired B cell proliferation in response to IgM and CD40 crosslinking, and
      attenuated antibody production to T-independent and T-dependent antigens.
      Deficiency of ST6Gal was further found to alter phosphotyrosine accumulation
      during signal transduction from the B lymphocyte antigen receptor. These studies
      reveal that the ST6Gal sialyltransferase and corresponding production of the
      Sia6LacNAc oligosaccharide are essential in promoting B lymphocyte activation and
      immune function.

PMID- 9539768
TI  - HLA-G expression in melanoma: a way for tumor cells to escape from
      immunosurveillance.
AB  - Considering the well established role of nonclassical HLA-G class I molecules in
      inhibiting natural killer (NK) cell function, the consequence of abnormal HLA-G
      expression in malignant cells should be the escape of tumors from
      immunosurveillance. To examine this hypothesis, we analyzed HLA-G expression and
      NK sensitivity in human malignant melanoma cells. Our analysis of three melanoma
      cell lines and ex vivo biopsy demonstrated that (i) IGR and M74 human melanoma
      cell lines exhibit a high level of HLA-G transcription with differential HLA-G
      isoform transcription and protein expression patterns, (ii) a higher level of HLA
      G transcription ex vivo is detected in a skin melanoma metastasis biopsy compared
      with a healthy skin fragment from the same individual, and (iii) HLA-G protein
      isoforms other than membrane-bound HLA-G1 protect IGR from NK lysis. It thus
      appears of critical importance to consider the specific role of HLA-G expression
      in tumors in the design of future cancer immunotherapies.

PMID- 9539769
TI  - Cathepsins B and D are dispensable for major histocompatibility complex class II
      mediated antigen presentation.
AB  - Antigen presentation by major histocompatibility complex (MHC) class II molecules
      requires the participation of different proteases in the endocytic route to
      degrade endocytosed antigens as well as the MHC class II-associated invariant
      chain (Ii). Thus far, only the cysteine protease cathepsin (Cat) S appears
      essential for complete destruction of Ii. The enzymes involved in degradation of
      the antigens themselves remain to be identified. Degradation of antigens in vitro
      and experiments using protease inhibitors have suggested that Cat B and Cat D,
      two major aspartyl and cysteine proteases, respectively, are involved in antigen
      degradation. We have analyzed the antigen-presenting properties of cells derived
      from mice deficient in either Cat B or Cat D. Although the absence of these
      proteases provoked a modest shift in the efficiency of presentation of some
      antigenic determinants, the overall capacity of Cat B-/- or Cat D-/- antigen
      presenting cells was unaffected. Degradation of Ii proceeded normally in Cat B-/-
      splenocytes, as it did in Cat D-/- cells. We conclude that neither Cat B nor Cat
      D are essential for MHC class II-mediated antigen presentation.

PMID- 9539770
TI  - T cell positive selection by a high density, low affinity ligand.
AB  - Interaction of the alpha beta T cell receptor (TCR) with major histocompatibility
      (MHC) molecules occupied with any of a large collection of peptides derived from
      self proteins is a critical step in driving T cell "positive" selection in the
      thymus. Interaction with this same pool of self-peptide/MHC ligands deletes T
      cells with potential self-reactivity. To examine how T cells survive both of
      these processes to form a self-tolerant mature repertoire, mice were constructed
      whose entire class II MHC IEk specific repertoire was positively selected on a
      single peptide covalently attached to the IEk molecule. In these mice T cells
      were identified that could respond to a variant of the positively selecting
      peptide bound to IEk. The affinities of the TCRs from these T cells for the
      positively selecting ligand were extremely low and at least 10-fold less than
      those for the activating ligand. These results support the theory that positive
      selection is driven by TCR affinities lower than those involved in T cell
      deletion or activation and that, if present at high concentration, even very low
      affinity ligands can positively select.

PMID- 9539771
TI  - Copresentation of natural HIV-1 agonist and antagonist ligands fails to induce
      the T cell receptor signaling cascade.
AB  - It is not known how human immunodeficiency virus type 1 (HIV-1)-derived
      antagonist peptides interfere with intracellular activation of cytotoxic T
      lymphocytes (CTL). We identified Gag epitope variants in HIV-1-infected patients
      that act as antagonists of CTL responses to unmutated epitopes. We then
      investigated the effect that presentation of each variant has on the early events
      of T cell receptor (TCR) signal transduction. We found that altered peptide
      ligands (APL) failed to induce phosphorylation of pp36, a crucial adaptor protein
      involved in TCR signal transduction. We further investigated the effect that
      simultaneous presentation of APL and native antigen at low, physiological,
      peptide concentrations (1 nM) has on TCR signal transduction, and we found that
      the presence of APL can completely inhibit induction of the protein tyrosine
      phosphorylation events of the TCR signal transduction cascade.

PMID- 9539772
TI  - T cell vaccination induces T cell receptor Vbeta-specific Qa-1-restricted
      regulatory CD8(+) T cells.
AB  - Vaccination of mice with activated autoantigen-reactive CD4(+) T cells (T cell
      vaccination, TCV) has been shown to induce protection from the subsequent
      induction of a variety of experimental autoimmune diseases, including
      experimental allergic encephalomyelitis (EAE). Although the mechanisms involved
      in TCV-mediated protection are not completely known, there is some evidence that
      TCV induces CD8(+) regulatory T cells that are specific for pathogenic CD4(+) T
      cells. Previously, we demonstrated that, after superantigen administration in
      vivo, CD8(+) T cells emerge that preferentially lyse and regulate activated
      autologous CD4(+) T cells in a T cell receptor (TCR) Vbeta-specific manner. This
      TCR Vbeta-specific regulation is not observed in beta2-microglobulin-deficient
      mice and is inhibited, in vitro, by antibody to Qa-1. We now show that similar
      Vbeta8-specific Qa-1-restricted CD8(+) T cells are also induced by TCV with
      activated CD4(+) Vbeta8(+) T cells. These CD8(+) T cells specifically lyse murine
      or human transfectants coexpressing Qa-1 and murine TCR Vbeta8. Further, CD8(+) T
      cell hybridoma clones generated from B10.PL mice vaccinated with a myelin basic
      protein-specific CD4(+)Vbeta8(+) T cell clone specifically recognize other CD4(+)
      T cells and T cell tumors that express Vbeta8 and the syngeneic Qa-1(a) but not
      the allogeneic Qa-1(b) molecule. Thus, Vbeta-specific Qa-1-restricted CD8(+) T
      cells are induced by activated CD4(+) T cells. We suggest that these CD8(+) T
      cells may function to specifically regulate activated CD4(+) T cells during
      immune responses.

PMID- 9539773
TI  - Alloantigen-induced unresponsiveness in cord blood T lymphocytes is associated
      with defective activation of Ras.
AB  - Human umbilical cord blood T lymphocytes (CBTL) respond to primary
      allostimulation but they do not proliferate upon rechallenge with alloantigen.
      Using PKH-26-labeled cells created a proliferative block that was observed only
      in CBTL that have divided during primary stimulation (PKH-26(dim)) but not in
      unstimulated (PKH-26(bright)) CBTL. CBTL's secondary unresponsiveness resembles
      anergy and can be overcome by treatment with phorbol myristate acetate (PMA) and
      ionomycin or by high doses (50-100 units/ml) of interleukin 2. Addition of
      interleukin 2 to the primary cultures does not prevent the induction of secondary
      unresponsiveness. Defective Ras activation is detected in PKH-26(dim) CBTL during
      secondary response to alloantigen or after antibody-mediated T cell receptor
      stimulation whereas Ras is activated and proliferation is induced in CBTL during
      primary alloantigenic stimulation. Upon stimulation with PMA plus ionomycin, PMA
      plus alloantigen, but not alloantigen plus ionomycin, Ras is activated in PKH
      26(dim) CBTL, and the block in proliferation is overcome. Correction of PKH
      26(dim) CBTL's proliferative defect correlates with PMA-induced Ras activation,
      suggesting a defect in the signaling pathway leading to Ras. Ras-independent
      signals, necessary but not sufficient to induce PKH-26(dim) CBTL proliferation,
      are provided by alloantigen exposure, as evident by the ability of PMA plus
      alloantigen but not PMA alone to overcome the proliferative block. Functional
      signal transduction through CD28 in PKH-26(dim) CBTL is supported by detectable
      CD28-mediated PI-3 kinase activation after PKH-26(dim) CBTL's exposure to
      alloantigen or CD28 cross-linking. These results suggest that defective
      activation of Ras plays a key role in PKH-26(dim) CBTL's secondary
      unresponsiveness and point to a defect along the T cell receptor rather than the
      CD28 signaling pathway.

PMID- 9539774
TI  - Low density lipoprotein receptor-negative mice expressing human apolipoprotein B
      100 develop complex atherosclerotic lesions on a chow diet: no accentuation by
      apolipoprotein(a).
AB  - We have generated mice with markedly elevated plasma levels of human low density
      lipoprotein (LDL) and reduced plasma levels of high density lipoprotein. These
      mice have no functional LDL receptors [LDLR-/-] and express a human
      apolipoprotein B-100 (apoB) transgene [Tg(apoB+/+)] with or without an apo(a)
      transgene [Tg(apoa+/-)]. Twenty animals (10 males and 10 females) of each of the
      following four genotypes were maintained on a chow diet: (i) LDLR-/-, (ii) LDLR-/
      ;Tg(apoa+/-), (iii) LDLR-/-;Tg(apoB+/+), and (iv)LDLR-/-;Tg(apoB+/+);Tg(apo+/-).
      The mice were killed at 6 mo, and the percent area of the aortic intimal surface
      that stained positive for neutral lipid was quantified. Mean percent areas of
      lipid staining were not significantly different between the LDLR-/- and LDLR-/
      ;Tg(apoa+/-) mice (1.0 +/- 0.2% vs. 1.4 +/- 0.3%). However, the LDLR-/
      ;Tg(apoB+/+) mice had approximately 15-fold greater mean lesion area than the
      LDLR-/- mice. No significant difference was found in percent lesion area in the
      LDLR-/-;Tg(apoB+/+) mice whether or not they expressed apo(a) [18.5 +/- 2.5%,
      without lipoprotein(a), Lp(a), vs. 16.0 +/- 1.7%, with Lp(a)]. Histochemical
      analyses of the sections from the proximal aorta of LDLR-/-;Tg(apoB+/+) mice
      revealed large, complex, lipid-laden atherosclerotic lesions that stained
      intensely with human apoB-100 antibodies. In mice expressing Lp(a), large amounts
      of apo(a) protein colocalized with apoB-100 in the lesions. We conclude that LDLR
      /-; Tg(apoB+/+) mice exhibit accelerated atherosclerosis on a chow diet and thus
      provide an excellent animal model in which to study atherosclerosis. We found no
      evidence that apo(a) increased atherosclerosis in this animal model.

PMID- 9539775
TI  - Selective killing of preneoplastic and neoplastic cells by methotrexate with
      leucovorin.
AB  - Three sublines of NIH 3T3 cells had the properties of non-neoplastic,
      preneoplastic, and neoplastic cells, respectively. The closer the cells were to
      neoplastic behavior, characterized by continuing growth at high density, the
      slower they multiplied at lower density. Under the conditions of high population
      density and low calf serum concentration used in the assay for transformed focus
      formation, the transformed or neoplastic cells were much more sensitive to
      killing by methotrexate (MTX) than were non-neoplastic cells in the same culture.
      This differential sensitivity of neoplastic cells was far more pronounced in
      molecular, cellular, and developmental biology medium 402 (MCDB 402) than in
      DMEM. It is associated with the presence in MCDB 402 of folinic acid, known
      clinically as leucovorin, which is a reduced form of the folic acid present in
      DMEM. Although leucovorin had been shown to selectively spare normal bone marrow
      and intestine in animals from the killing effect of MTX on tumor cells, we
      demonstrate the preferential killing of neoplastic over non-neoplastic cells of
      the same derivation. Neither neoplastic nor non-neoplastic cells were killed once
      they had stopped multiplying at their respective saturation densities. The
      development of the light foci characteristic of the preneoplastic cells was less
      sensitive to MTX than the formation of the dense foci produced by the fully
      neoplastic cells. The system should serve as a valuable model to establish basic
      principles and optimal conditions for selective killing of neoplastic cells by
      chemotherapeutic drugs.

PMID- 9539776
TI  - Overexpression of human copper, zinc-superoxide dismutase (SOD1) prevents
      postischemic injury.
AB  - Superoxide and superoxide-derived oxidants have been hypothesized to be important
      mediators of postischemic injury. Whereas copper, zinc-superoxide dismutase,
      SOD1, efficiently dismutates superoxide, there has been controversy regarding
      whether increasing intracellular SOD1 expression would protect against or
      potentiate cellular injury. To determine whether increased SOD1 protects the
      heart from ischemia and reperfusion, studies were performed in a newly developed
      transgenic mouse model in which direct measurement of superoxide, contractile
      function, bioenergetics, and cell death could be performed. Transgenic mice with
      overexpression of human SOD1 were studied along with matched nontransgenic
      controls. Immunoblotting and immunohistology demonstrated that total SOD1
      expression was increased 10-fold in hearts from transgenic mice compared with
      nontransgenic controls, with increased expression in both myocytes and
      endothelial cells. In nontransgenic hearts following 30 min of global ischemia a
      reperfusion-associated burst of superoxide generation was demonstrated by
      electron paramagnetic resonance spin trapping. However, in the transgenic hearts
      with overexpression of SOD1 the burst of superoxide generation was almost totally
      quenched, and this was accompanied by a 2-fold increase in the recovery of
      contractile function, a 2.2-fold decrease in infarct size, and a greatly improved
      recovery of high energy phosphates compared with that in nontransgenic controls.
      These results demonstrate that superoxide is an important mediator of
      postischemic injury and that increasing intracellular SOD1 dramatically protects
      the heart from this injury. Thus, increasing intracellular SOD1 expression may be
      a highly effective approach to decrease the cellular injury that occurs following
      reperfusion of ischemic tissues.

PMID- 9539777
TI  - The tetravalent guanylhydrazone CNI-1493 blocks the toxic effects of interleukin
      2 without diminishing antitumor efficacy.
AB  - The use of interleukin 2 (IL-2) as an antineoplastic agent has been limited by
      the serious toxicities that accompany the doses necessary for a tumor response.
      Elevation of nitric oxide (NO) and tumor necrosis factor (TNF) both have been
      implicated in IL-2 toxicities. CNI-1493, a tetravalent guanylhydrazone, is an
      inhibitor of macrophage activation including the synthesis of TNF and other
      cytokines. Doses of CNI-1493 as low as 1 mg/kg/day conferred complete protection
      against fatal toxicity of IL-2 with IL-2 doses tenfold higher than the safely
      tolerated level in Sprague-Dawley rats. Moreover, typical pathologic changes in
      the lungs, kidneys, and the liver caused by IL-2 infusion were blocked by
      cotreatment with CNI-1493. When animals bearing established hepatomas were given
      IL-2 and CNI-1493 combination therapy, 10 of 10 hepatomas regressed from 1 cm3 to
      <1 mm3. Intracytoplasmic TNF levels were increased in normal tissues from IL-2
      treated animals, and treatment with CNI-1493 maintained TNF at control levels.
      The degree of apoptosis measured by terminal deoxynucleotidyltransferase-mediated
      dUTP-biotin nick end labeling staining of tumors following IL-2 therapy was not
      reduced compared with IL-2 cotreated with CNI-1493. In contrast, apoptosis in the
      liver and lung parenchyma following IL-2 therapy was blocked completely by
      cotreatment with CNI-1493. Taken together, these data showed that low and
      infrequent doses of CNI-1493 markedly protected animals from IL-2 systemic
      toxicities whereas not affecting tumor response to IL-2 therapy. With the
      protection afforded by CNI-1493 treatment, IL-2 therapy dose levels could be
      increased to provide significant antitumor effects in animals with established
      hepatomas.

PMID- 9539778
TI  - Activating mutations in the extracellular domain of the fibroblast growth factor
      receptor 2 function by disruption of the disulfide bond in the third
      immunoglobulin-like domain.
AB  - Multiple human skeletal and craniosynostosis disorders, including Crouzon,
      Pfeiffer, Jackson-Weiss, and Apert syndromes, result from numerous point
      mutations in the extracellular region of fibroblast growth factor receptor 2
      (FGFR2). Many of these mutations create a free cysteine residue that potentially
      leads to abnormal disulfide bond formation and receptor activation; however, for
      noncysteine mutations, the mechanism of receptor activation remains unclear. We
      examined the effect of two of these mutations, W290G and T341P, on receptor
      dimerization and activation. These mutations resulted in cellular transformation
      when expressed as FGFR2/Neu chimeric receptors. Additionally, in full-length
      FGFR2, the mutations induced receptor dimerization and elevated levels of
      tyrosine kinase activity. Interestingly, transformation by the chimeric
      receptors, dimerization, and enhanced kinase activity were all abolished if
      either the W290G or the T341P mutation was expressed in conjunction with
      mutations that eliminate the disulfide bond in the third immunoglobulin-like
      domain (Ig-3). These results demonstrate a requirement for the Ig-3 cysteine
      residues in the activation of FGFR2 by noncysteine mutations. Molecular modeling
      also reveals that noncysteine mutations may activate FGFR2 by altering the
      conformation of the Ig-3 domain near the disulfide bond, preventing the formation
      of an intramolecular bond. This allows the unbonded cysteine residues to
      participate in intermolecular disulfide bonding, resulting in constitutive
      activation of the receptor.

PMID- 9539779
TI  - Identification and characterization of the ARP1 gene, a target for the human
      acute leukemia ALL1 gene.
AB  - ALL1, the human homologue of Drosophila trithorax, is directly involved in human
      acute leukemias associated with abnormalities at 11q23. Using the differential
      display method, we isolated a gene that is down-regulated in All1 double-knockout
      mouse embryonic stem (ES) cells. The gene, designated ARP1 (also termed RIEG,
      Ptx2, or Otlx2), is a member of a family of homeotic genes containing a short
      motif shared with several homeobox genes. Using a bacterially synthesized All1
      polypeptide encompassing the AT-hook motifs, we identified a 0.5-kb ARP1 DNA
      fragment that preferentially bound to the polypeptide. Within this DNA, a region
      of approximately 100 bp was protected by the polypeptide from digestion with
      ExoIII and DNase I. Whole-mount in situ hybridization to early mouse embryos of
      9.5-10.5 days indicated a complex pattern of Arp1 expression spatially
      overlapping with the expression of All1. Although the ARP1 gene is expressed
      strongly in bone marrow cells, no transcripts were detected in six leukemia cell
      lines with 11q23 translocations. These results suggest that ARP1 is up-regulated
      by the All1 protein, possibly through direct interaction with an upstream DNA
      sequence of the former. The results are also consistent with the suggestion that
      ALL1 chimeric proteins resulting from 11q23 abnormalities act in a dominant
      negative fashion.

PMID- 9539780
TI  - Chimeric anti-angiogenin antibody cAb 26-2F inhibits the formation of human
      breast cancer xenografts in athymic mice.
AB  - Angiogenin (Ang), an inducer of neovascularization, is secreted by several types
      of human tumor cells and appears critical for their growth. The murine anti-Ang
      monoclonal antibody (mAb) 26-2F neutralizes the activities of Ang and
      dramatically prevents the establishment and metastatic dissemination of human
      tumor cell xenografts in athymic mice. However, for use clinically, the well
      documented problem of the human anti-globulin antibody response known to occur
      with murine antibodies requires resolution. As a result, chimeric as well as
      totally humanized antibodies are currently being evaluated as therapeutic agents
      for the treatment of several pathological conditions, including malignancy.
      Therefore, we have constructed a chimeric mouse/human antibody based on the
      structure of mAb 26-2F. Complementary DNAs from the light and heavy chain
      variable regions of mAb 26-2F were cloned, sequenced, and genetically engineered
      by PCR for subcloning into expression vectors that contain human constant region
      sequences. Transfection of these vectors into nonproducing mouse myeloma cells
      resulted in the secretion of fully assembled tetrameric molecules. The chimeric
      antibody (cAb 26-2F) binds to Ang and inhibits its ribonucleolytic and angiogenic
      activities as potently as mAb 26-2F. Furthermore, the capacities of cAb 26-2F and
      its murine counterpart to suppress the formation of human breast cancer tumors in
      athymic mice are indistinguishable. Thus cAb 26-2F, with its retained
      neutralization capability and likely decreased immunogenicity, may be of use
      clinically for the treatment of human cancer and related disorders where
      pathological angiogenesis is a component.

PMID- 9539781
TI  - Fetal origins of the TEL-AML1 fusion gene in identical twins with leukemia.
AB  - The TEL (ETV6)-AML1 (CBFA2) gene fusion is the most common reciprocal chromosomal
      rearrangement in childhood cancer occurring in approximately 25% of the most
      predominant subtype of leukemia- common acute lymphoblastic leukemia. The TEL
      AML1 genomic sequence has been characterized in a pair of monozygotic twins
      diagnosed at ages 3 years, 6 months and 4 years, 10 months with common acute
      lymphoblastic leukemia. The twin leukemic DNA shared the same unique (or
      clonotypic) but nonconstitutive TEL-AML1 fusion sequence. The most plausible
      explanation for this finding is a single cell origin of the TEL-AML fusion in one
      fetus in utero, probably as a leukemia-initiating mutation, followed by
      intraplacental metastasis of clonal progeny to the other twin. Clonal identity is
      further supported by the finding that the leukemic cells in the two twins shared
      an identical rearranged IGH allele. These data have implications for the etiology
      and natural history of childhood leukemia.

PMID- 9539782
TI  - Detection and characterization of carcinoma cells in the blood.
AB  - A highly sensitive assay combining immunomagnetic enrichment with multiparameter
      flow cytometric and immunocytochemical analysis has been developed to detect,
      enumerate, and characterize carcinoma cells in the blood. The assay can detect
      one epithelial cell or less in 1 ml of blood. Peripheral blood (10-20 ml) from 30
      patients with carcinoma of the breast, from 3 patients with prostate cancer, and
      from 13 controls was examined by flow cytometry for the presence of circulating
      epithelial cells defined as nucleic acid+, CD45(-), and cytokeratin+. Highly
      significant differences in the number of circulating epithelial cells were found
      between normal controls and patients with cancer including 17 with organ-confined
      disease. To determine whether the circulating epithelial cells in the cancer
      patients were neoplastic cells, cytospin preparations were made after
      immunomagnetic enrichment and were analyzed. Epithelial cells from patients with
      breast cancer generally stained with mAbs against cytokeratin and 3 of 5 for
      mucin-1. In contrast, no cells that stained for these antigens were observed in
      the blood from normal controls. The morphology of the stained cells was
      consistent with that of neoplastic cells. Of 8 patients with breast cancer
      followed for 1-10 months, there was a good correlation between changes in the
      level of tumor cells in the blood with both treatment with chemotherapy and
      clinical status. The present assay may be helpful in early detection, in
      monitoring disease, and in prognostication.

PMID- 9539783
TI  - Extracellular HIV-1 virus protein R causes a large inward current and cell death
      in cultured hippocampal neurons: implications for AIDS pathology.
AB  - The small HIV-1 accessory protein Vpr (virus protein R) is a multifunctional
      protein that is present in the serum and cerebrospinal fluid of AIDS patients. We
      previously showed that Vpr can form cation-selective ion channels across planar
      lipid bilayers, introducing the possibility that, if incorporated into the
      membranes of living cells, Vpr might form ion channels and consequently perturb
      the maintained ionic gradient. In this study, we demonstrate, by a variety of
      approaches, that Vpr added extracellularly to intact cells does indeed form ion
      channels. We use confocal laser scanning microscopy to examine the subcellular
      localization of fluorescently labeled Vpr. Plasmalemma depolarization and damage
      are examined using the anionic potential-sensitive dye bis(1,3-dibutylbarbituric
      acid) trimethine oxonol and propidium iodide (PI), respectively, and the effect
      of Vpr on whole-cell current is demonstrated directly by using the patch-clamp
      technique. We show that recombinant purified extracellular Vpr associates with
      the plasmalemma of hippocampal neurons to cause a large inward cation current and
      depolarization of the plasmalemma, eventually resulting in cell death. Thus, we
      demonstrate a physiological action of extracellular Vpr and present its
      mechanistic basis. These findings may have important implications for
      neuropathologies in AIDS patients who possess significant amounts of Vpr in the
      cerebrospinal fluid.

PMID- 9539784
TI  - Different mechanisms for suppression of apoptosis by cytokines and calcium
      mobilizing compounds.
AB  - Overexpression of wild-type p53 in M1 myeloid leukemia cells induces apoptotic
      cell death that was suppressed by the calcium ionophore A23187 and the calcium
      ATPase inhibitor thapsigargin (TG). This suppression of apoptosis by A23187 or TG
      was associated with suppression of caspase activation but not with suppression of
      wild-type-p53-induced expression of WAF-1, mdm-2, or FAS. In contrast to
      suppression of apoptosis by the cytokines interleukin 6 (IL-6) and interferon
      gamma, a protease inhibitor, or an antioxidant, suppression of apoptosis by
      A23187 or TG required extracellular Ca2+ and was specifically abolished by the
      calcineurin inhibitor cyclosporin A. IL-6 induced immediate early activation of
      junB and zif/268 (Egr-1) but A23187 and TG did not. A23187 and TG also suppressed
      induction of apoptosis by doxorubicin or vincristine in M1 cells that did not
      express p53 by a cyclosporin A-sensitive mechanism. Suppression of apoptosis by
      A23187 or TG was not associated with autocrine production of IL-6. Apoptosis
      induced in IL-6-primed M1 cells after IL-6 withdrawal was not suppressed by
      A23187 or TG but was suppressed by the cytokines IL-6, IL-3, or interferon gamma.
      The results indicate that these Ca2+-mobilizing compounds can suppress some
      pathways of apoptosis suppressed by cytokines but do so by a different mechanism.

PMID- 9539785
TI  - Regulation of transport pathways in tumor vessels: role of tumor type and
      microenvironment.
AB  - Novel anti-neoplastic agents such as gene targeting vectors and encapsulated
      carriers are quite large (approximately 100-300 nm in diameter). An understanding
      of the functional size and physiological regulation of transvascular pathways is
      necessary to optimize delivery of these agents. Here we analyze the functional
      limits of transvascular transport and its modulation by the microenvironment. One
      human and five murine tumors including mammary and colorectal carcinomas,
      hepatoma, glioma, and sarcoma were implanted in the dorsal skin-fold chamber or
      cranial window, and the pore cutoff size, a functional measure of transvascular
      gap size, was determined. The microenvironment was modulated: (i) spatially, by
      growing tumors in subcutaneous or cranial locations and (ii) temporally, by
      inducing vascular regression in hormone-dependent tumors. Tumors grown
      subcutaneously exhibited a characteristic pore cutoff size ranging from 200 nm to
      1.2 microm. This pore cutoff size was reduced in tumors grown in the cranium or
      in regressing tumors after hormone withdrawal. Vessels induced in basic
      fibroblast growth factor-containing gels had a pore cutoff size of 200 nm.
      Albumin permeability was independent of pore cutoff size. These results have
      three major implications for the delivery of therapeutic agents: (i) delivery may
      be less efficient in cranial tumors than in subcutaneous tumors, (ii) delivery
      may be reduced during tumor regression induced by hormonal ablation, and (iii)
      permeability to a molecule is independent of pore cutoff size as long as the
      diameter of the molecule is much less than the pore diameter.

PMID- 9539786
TI  - Direct adenovirus-mediated gene transfer of interleukin 1 and tumor necrosis
      factor alpha soluble receptors to rabbit knees with experimental arthritis has
      local and distal anti-arthritic effects.
AB  - Adenoviral vectors were used to deliver genes encoding a soluble interleukin 1
      (IL-1)-type I receptor-IgG fusion protein and/or a soluble type I tumor necrosis
      factor alpha (TNFalpha) receptor-IgG fusion protein directly to the knees of
      rabbits with antigen-induced arthritis. When tested individually, knees receiving
      the soluble IL-1 receptor had significantly reduced cartilage matrix degradation
      and white blood cell infiltration into the joint space. Delivery of the soluble
      TNFalpha receptor was less effective, having only a moderate effect on white
      blood cell infiltration and no effect on cartilage breakdown. When both soluble
      receptors were used together, there was a greater inhibition of white blood cell
      infiltration and cartilage breakdown with a considerable reduction of synovitis.
      Interestingly, anti-arthritic effects were also seen in contralateral control
      knees receiving only a marker gene, suggesting that sustained local inhibition of
      disease activity in one joint may confer an anti-arthritic effect on other
      joints. These results suggest that local intra-articular gene transfer could be
      used to treat systemic polyarticular arthritides.

PMID- 9539787
TI  - Targeted mutation reveals a central role for SR-BI in hepatic selective uptake of
      high density lipoprotein cholesterol.
AB  - Scavenger receptor BI (SR-BI) is a cell surface receptor that binds high density
      lipoproteins (HDL) and mediates selective uptake of HDL cholesteryl esters (CE)
      in transfected cells. To address the physiological role of SR-BI in HDL
      cholesterol homeostasis, mice were generated bearing an SR-BI promoter mutation
      that resulted in decreased expression of the receptor in homozygous mutant
      (designated SR-BI att) mice. Hepatic expression of the receptor was reduced by
      53% with a corresponding increase in total plasma cholesterol levels of 50-70% in
      SR-BI att mice, attributable almost exclusively to elevated plasma HDL. In
      addition to increased HDL-CE, HDL phospholipids and apo A-1 levels were elevated,
      and there was an increase in HDL particle size in mutant mice. Metabolic studies
      using HDL bearing nondegradable radiolabels in both the protein and lipid
      components demonstrated that reducing hepatic SR-BI expression by half was
      associated with a decrease of 47% in selective uptake of CE by the liver, and a
      corresponding reduction of 53% in selective removal of HDL-CE from plasma. Taken
      together, these findings strongly support a pivotal role for hepatic SR-BI
      expression in regulating plasma HDL levels and indicate that SR-BI is the major
      molecule mediating selective CE uptake by the liver. The inverse correlation
      between plasma HDL levels and atherosclerosis further suggests that SR-BI may
      influence the development of coronary artery disease.

PMID- 9539788
TI  - An antagonistic vascular endothelial growth factor (VEGF) variant inhibits VEGF
      stimulated receptor autophosphorylation and proliferation of human endothelial
      cells.
AB  - Vascular endothelial growth factor (VEGF) is a potent mitogen with a unique
      specificity for endothelial cells and a key mediator of aberrant endothelial cell
      proliferation and vascular permeability in a variety of human pathological
      situations, such as tumor angiogenesis, diabetic retinopathy, rheumatoid
      arthritis, or psoriasis. VEGF is a symmetric homodimeric molecule with two
      receptor binding interfaces lying on each pole of the molecule. Herein we report
      on the construction and recombinant expression of an asymmetric heterodimeric
      VEGF variant with an intact receptor binding interface at one pole and a mutant
      receptor binding interface at the second pole of the dimer. This VEGF variant
      binds to VEGF receptors but fails to induce receptor activation. In competition
      experiments, the heterodimeric VEGF variant antagonizes VEGF-stimulated receptor
      autophosphorylation and proliferation of endothelial cells. A 15-fold excess of
      the heterodimer was sufficient to inhibit VEGF-stimulated endothelial cell
      proliferation by 50%, and a 100-fold excess resulted in an almost complete
      inhibition. By using a rational approach that is based on the structure of VEGF,
      we have shown the feasibility to construct a VEGF variant that acts as an VEGF
      antagonist.

PMID- 9539789
TI  - Breakers of advanced glycation end products restore large artery properties in
      experimental diabetes.
AB  - Glucose and other reducing sugars react with proteins by a nonenzymatic,
      posttranslational modification process called nonenzymatic glycation. The
      formation of advanced glycation end products (AGEs) on connective tissue and
      matrix components accounts largely for the increase in collagen crosslinking that
      accompanies normal aging and which occurs at an accelerated rate in diabetes,
      leading to an increase in arterial stiffness. A new class of AGE crosslink
      "breakers" reacts with and cleaves these covalent, AGE-derived protein
      crosslinks. Treatment of rats with streptozotocin-induced diabetes with the AGE
      breaker ALT-711 for 1-3 weeks reversed the diabetes-induced increase of large
      artery stiffness as measured by systemic arterial compliance, aortic impedance,
      and carotid artery compliance and distensibility. These findings will have
      considerable implications for the treatment of patients with diabetes-related
      complications and aging.

PMID- 9539790
TI  - In vivo evidence that erythropoietin protects neurons from ischemic damage.
AB  - Erythropoietin (EPO) produced by the kidney and the liver (in fetuses) stimulates
      erythropoiesis. In the central nervous system, neurons express EPO receptor
      (EPOR) and astrocytes produce EPO. EPO has been shown to protect primary cultured
      neurons from N-methyl-D-aspartate (NMDA) receptor-mediated glutamate toxicity.
      Here we report in vivo evidence that EPO protects neurons against ischemia
      induced cell death. Infusion of EPO into the lateral ventricles of gerbils
      prevented ischemia-induced learning disability and rescued hippocampal CA1
      neurons from lethal ischemic damage. The neuroprotective action of exogenous EPO
      was also confirmed by counting synapses in the hippocampal CA1 region. Infusion
      of soluble EPOR (an extracellular domain capable of binding with the ligand) into
      animals given a mild ischemic treatment that did not produce neuronal damage,
      caused neuronal degeneration and impaired learning ability, whereas infusion of
      the heat-denatured soluble EPOR was not detrimental, demonstrating that the
      endogenous brain EPO is crucial for neuronal survival. The presence of EPO in
      neuron cultures did not repress a NMDA receptor-mediated increase in
      intracellular Ca2+, but rescued the neurons from NO-induced death. Taken together
      EPO may exert its neuroprotective effect by reducing the NO-mediated formation of
      free radicals or antagonizing their toxicity.

PMID- 9539791
TI  - Differential patterns of acquired virulence genes distinguish Salmonella strains.
AB  - Analysis of several Salmonella typhimurium in vivo-induced genes located in
      regions of atypical base composition has uncovered acquired genetic elements that
      cumulatively engender pathogenicity. Many of these regions are associated with
      mobile elements, encode predicted adhesin and invasin-like functions, and are
      required for full virulence. Some of these regions distinguish broad host range
      from host-adapted Salmonella serovars and may contribute to inherent differences
      in host specificity, tissue tropism, and disease manifestation. Maintenance of
      this archipelago of acquired sequence by selection in specific hosts reveals a
      fossil record of the evolution of pathogenic species.

PMID- 9539792
TI  - NF-kappa B-dependent inhibition of apoptosis is essential for host cellsurvival
      during Rickettsia rickettsii infection.
AB  - The possibility that bacteria may have evolved strategies to overcome host cell
      apoptosis was explored by using Rickettsia rickettsii, an obligate intracellular
      Gram-negative bacteria that is the etiologic agent of Rocky Mountain spotted
      fever. The vascular endothelial cell, the primary target cell during in vivo
      infection, exhibits no evidence of apoptosis during natural infection and is
      maintained for a sufficient time to allow replication and cell-to-cell spread
      prior to eventual death due to necrotic damage. Prior work in our laboratory
      demonstrated that R. rickettsii infection activates the transcription factor NF
      kappa B and alters expression of several genes under its control. However, when
      R. rickettsii-induced activation of NF-kappa B was inhibited, apoptosis of
      infected but not uninfected endothelial cells rapidly ensued. In addition, human
      embryonic fibroblasts stably transfected with a superrepressor mutant inhibitory
      subunit Ikappa B that rendered NF-kappa B inactivatable also underwent apoptosis
      when infected, whereas infected wild-type human embryonic fibroblasts survived.
      R. rickettsii, therefore, appeared to inhibit host cell apoptosis via a mechanism
      dependent on NF-kappa B activation. Apoptotic nuclear changes correlated with
      presence of intracellular organisms and thus this previously unrecognized
      proapoptotic signal, masked by concomitant NF-kappa B activation, likely required
      intracellular infection. Our studies demonstrate that a bacterial organism can
      exert an antiapoptotic effect, thus modulating the host cell's apoptotic response
      to its own advantage by potentially allowing the host cell to remain as a site of
      infection.

PMID- 9539793
TI  - Bipolar localization of Bacillus subtilis topoisomerase IV, an enzyme required
      for chromosome segregation.
AB  - In Bacillus subtilis, parE and parC were shown to be essential genes for the
      segregation of replicated chromosomes. Disruption of either one of these genes
      resulted in failure of the nucleoid to segregate. Purified ParE and ParC proteins
      reconstituted to form topoisomerase IV (topo IV), which was highly proficient for
      ATP-dependent superhelical DNA relaxation and decatenation of interlocked DNA
      networks. By immunofluorescence microscopy and by directly visualizing
      fluorescence by using green fluorescence protein fusions, we determined that ParC
      is localized at the poles of the bacteria in rapidly growing cultures. The
      bipolar localization of ParC required functional ParE, suggesting that topo IV
      activity is required for the localization. ParE was found to be distributed
      uniformly throughout the cell. On the other hand, fluorescence microscopy showed
      that the GyrA and GyrB subunits of gyrase were associated with the nucleoid. Our
      results provide a physiologic distinction between DNA gyrase and topo IV. The
      subcellular localization of topo IV provides physical evidence that it may be
      part of the bacterial segregation machinery.

PMID- 9539794
TI  - Latent varicella-zoster virus is located predominantly in neurons in human
      trigeminal ganglia.
AB  - Varicella-zoster virus (VZV) is a human herpesvirus that causes varicella
      (chicken pox) as a primary infection and, after a variable period of latency in
      trigeminal and dorsal root ganglia, reactivates to cause herpes zoster
      (shingles). Both of these conditions may be followed by a variety of neurological
      complications, especially in immunocompromised individuals such as those with
      human immunodeficiency virus (HIV) infection. There have been a number of
      conflicting reports regarding the cellular location of latent VZV within human
      ganglia. To address this controversy we examined fixed wax-embedded trigeminal
      ganglia from 30 individuals obtained at autopsy, including 11 with HIV infection,
      2 neonates, and 17 immunocompetent individuals, for the presence of latent VZV.
      Polymerase chain reaction (PCR), in situ hybridization, and PCR in situ
      amplification techniques with oligonucleotide probes and primer sequences to VZV
      genes 18, 21, 29, and 63 were used. VZV DNA in ganglia was detected in 15
      individuals by using PCR alone, and in 12 individuals (6 normal non-HIV and 6
      positive HIV individuals, but not neonatal ganglia) by using PCR in situ
      amplification. When in situ hybridization alone was used, 5 HIV-positive
      individuals and only 1 non-HIV individual showed VZV nucleic acid signals in
      ganglia. In all of the VZV-positive ganglia examined, VZV nucleic acid was
      detected in neuronal nuclei. Only occasional nonneuronal cells contained VZV DNA.
      We conclude from these studies that the neuron is the predominant site of latent
      VZV in human trigeminal ganglia.

PMID- 9539795
TI  - Functions of the two glutamate transporters GLAST and GLT-1 in the retina.
AB  - In the retina, the glutamate transporter GLAST is expressed in Muller cells,
      whereas the glutamate transporter GLT-1 is found only in cones and various types
      of bipolar cells. To investigate the functional role of this differential
      distribution of glutamate transporters, we have analyzed GLAST and GLT-1 mutant
      mice. In GLAST-deficient mice, the electroretinogram b-wave and oscillatory
      potentials are reduced and retinal damage after ischemia is exacerbated, whereas
      GLT-1-deficient mice show almost normal electroretinograms and mild increased
      retinal damage after ischemia. These results demonstrate that GLAST is required
      for normal signal transmission between photoreceptors and bipolar cells and that
      both GLAST and GLT-1 play a neuroprotective role during ischemia in the retina.

PMID- 9539797
TI  - Src interacts with dynamin and synapsin in neuronal cells.
AB  - The nonreceptor tyrosine kinase Src is expressed at a high level in cells that
      are specialized for regulated secretion, such as the neuron, and is concentrated
      on secretory vesicles or at the site of exocytosis. To investigate the
      possibility that Src may play a role in regulating membrane traffic, we searched
      for neuronal proteins that will interact with Src. The SH3 domain of Src, but not
      that of the splice variant N-Src, bound to three proteins from mouse synaptosomes
      or PC12 cells: dynamin, synapsin Ia, and synapsin Ib. Dynamin and the synapsins
      coprecipitated with Src from PC12 cell extracts, and they colocalized with a
      subset of Src in the PC12 cell by immunofluorescence. Neither dynamin nor the
      synapsins were phosphorylated by Src, suggesting that the interaction of these
      proteins serves to direct the kinase activity of Src toward other proteins in the
      vesicle population. In immunoprecipitates containing Src and dynamin, the
      clathrin adaptor protein alpha-adaptin was also found. The association of Src and
      synapsin suggests a role for Src in the life cycle of the synaptic vesicle. The
      identification of a complex containing Src, dynamin, and alpha-adaptin indicates
      that Src may play a more general role in membrane traffic as well.

PMID- 9539796
TI  - A third member of the synapsin gene family.
AB  - Synapsins are a family of neuron-specific synaptic vesicle-associated
      phosphoproteins that have been implicated in synaptogenesis and in the modulation
      of neurotransmitter release. In mammals, distinct genes for synapsins I and II
      have been identified, each of which gives rise to two alternatively spliced
      isoforms. We have now cloned and characterized a third member of the synapsin
      gene family, synapsin III, from human DNA. Synapsin III gives rise to at least
      one protein isoform, designated synapsin IIIa, in several mammalian species.
      Synapsin IIIa is associated with synaptic vesicles, and its expression appears to
      be neuron-specific. The primary structure of synapsin IIIa conforms to the domain
      model previously described for the synapsin family, with domains A, C, and E
      exhibiting the highest degree of conservation. Synapsin IIIa contains a novel
      domain, termed domain J, located between domains C and E. The similarities among
      synapsins I, II, and III in domain organization, neuron-specific expression, and
      subcellular localization suggest a possible role for synapsin III in the
      regulation of neurotransmitter release and synaptogenesis. The human synapsin III
      gene is located on chromosome 22q12-13, which has been identified as a possible
      schizophrenia susceptibility locus. On the basis of this localization and the
      well established neurobiological roles of the synapsins, synapsin III represents
      a candidate gene for schizophrenia.

PMID- 9539798
TI  - Dehydroepiandrosterone: a potential signalling molecule for neocortical
      organization during development.
AB  - Dehydroepiandrosterone (DHEA) and its sulfate derivative (DHEAS) are the most
      abundant steroids produced by the human adrenal, but no receptors have been
      identified for these steroids, and no function for them has been established,
      other than as precursors for sex steroid synthesis. DHEA and DHEAS are found in
      brains from many species, and we have shown that enzymes crucial for their
      synthesis, especially P450c17 (17alpha-hydroxylase/c17,20 lyase), are expressed
      in a developmentally regulated, region-specific fashion in the developing rodent
      brain. One region of embryonic expression of P450c17, the neocortical subplate,
      has been postulated to play a role in guiding cortical projections to their
      appropriate targets. We therefore determined if products of P450c17 activity,
      DHEA and DHEAS, regulated the motility and/or growth of neocortical neurons. In
      primary cultures of mouse embryonic neocortical neurons, DHEA increased the
      length of neurites containing the axonal marker Tau-1, and the incidence of
      varicosities and basket-like process formations in a dose-dependent fashion.
      These effects could be seen at concentrations normally found in the brain. By
      contrast, DHEAS had no effect on Tau-1 axonal neurites but increased the length
      of neurites containing the dendritic marker microtubule-associated protein-2.
      DHEA rapidly increased free intracellular calcium via activation of N-methyl-D
      aspartate (NMDA) receptors. These studies provide evidence of mechanisms by which
      DHEA and DHEAS exert biological actions, show that they have specific functions
      other than as sex steroid precursors, mediate their effects via non-classic
      steroid hormone receptors, and suggest that their developmentally regulated
      synthesis in vivo may play crucial and different roles in organizing the
      neocortex.

PMID- 9539799
TI  - Submicrosecond pacemaker precision is behaviorally modulated: the gymnotiform
      electromotor pathway.
AB  - What are the limits and modulators of neural precision? We address this question
      in the most regular biological oscillator known, the electric organ command
      nucleus in the brainstem of wave-type gymnotiform fish. These fish produce an
      oscillating electric field, the electric organ discharge (EOD), used in
      electrolocation and communication. We show here that the EOD precision, measured
      by the coefficient of variation (CV = SD/mean period) is as low as 2 x 10(-4) in
      five species representing three families that range widely in species and
      individual mean EOD frequencies (70-1,250 Hz). Intracellular recording in the
      pacemaker nucleus (Pn), which commands the EOD cycle by cycle, revealed that
      individual Pn neurons of the same species also display an extremely low CV (CV =
      6 x 10(-4), 0.8 micro sec SD). Although the EOD CV can remain at its minimum for
      hours, it varies with novel environmental conditions, during communication, and
      spontaneously. Spontaneous changes occur as abrupt steps (250 ms), oscillations
      (3-5 Hz), or slow ramps (10-30 s). Several findings suggest that these changes
      are under active control and depend on behavioral state: mean EOD frequency and
      CV can change independently; CV often decreases in response to behavioral
      stimuli; and lesions of one of the two inputs to the Pn had more influence on CV
      than lesions of the other input.

PMID- 9539800
TI  - Unique regulatory properties of the type 2a Ca2+ channel beta subunit caused by
      palmitoylation.
AB  - Beta subunits of voltage-gated Ca2+ channels are encoded in four genes and
      display additional molecular diversity because of alternative splicing. At the
      functional level, all forms are very similar except for beta2a, which differs in
      that it does not support prepulse facilitation of alpha1C Ca2+ channels, inhibits
      voltage-induced inactivation of neuronal alpha1E Ca2+ channels, and is more
      effective in blocking inhibition of alpha1E channels by G protein-coupled
      receptors. We show that the distinguishing properties of beta2a, rather than
      interaction with a distinct site of alpha1, are because of the recently described
      palmitoylation of cysteines in positions three and four, which also occurs in the
      Xenopus oocyte. Essentially, all of the distinguishing features of beta2a were
      lost in a mutant that could not be palmitoylated [beta2a(Cys3,4Ser)]. Because
      protein palmitoylation is a dynamic process, these findings point to the
      possibility that regulation of palmitoylation may contribute to activity
      dependent neuronal and synaptic plasticity. Evidence is presented that there may
      exist as many as three beta2 splice variants differing only in their N-termini.

PMID- 9539802
TI  - Long-term potentiation and dual-component quantal signaling in the dentate gyrus.
AB  - Long-term potentiation (LTP) of excitatory transmission is an important candidate
      cellular mechanism for the storage of memories in the mammalian brain. The
      subcellular phenomena that underlie the persistent increase in synaptic strength,
      however, are incompletely understood. A potentially powerful method to detect a
      presynaptic increase in glutamate release is to examine the effect of LTP
      induction on the rate at which the use-dependent blocker MK-801 attenuates
      successive N-methyl-D-aspartic acid (NMDA) receptor-mediated synaptic signals.
      This method, however, has given apparently contradictory results when applied in
      hippocampal CA1. The inconsistency could be explained if NMDA receptors were
      opened by glutamate not only released from local presynaptic terminals, but also
      diffusing from synapses on neighboring cells where LTP was not induced. Here we
      examine the effect of pairing-induced LTP on the MK-801 blocking rate in two
      afferent inputs to dentate granule cells. LTP in the medial perforant path is
      associated with a significant increase in the MK-801 blocking rate, implying a
      presynaptic increase in glutamate release probability. An enhanced MK-801
      blocking rate is not seen, however, in the lateral perforant path. This result
      still could be compatible with a presynaptic contribution to LTP in the lateral
      perforant path if intersynaptic cross-talk occurred. In support of this
      hypothesis, we show that NMDA receptors consistently sense more quanta of
      glutamate than do alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid
      receptors. In the medial perforant path, in contrast, there is no significant
      difference in the number of quanta mediated by the two receptors. These results
      support a presynaptic contribution to LTP and imply that differences in
      intersynaptic cross-talk can complicate the interpretation of experiments
      designed to detect changes in transmitter release.

PMID- 9539801
TI  - An isoform of the rod photoreceptor cyclic nucleotide-gated channel beta subunit
      expressed in olfactory neurons.
AB  - Sensory transduction in olfactory neurons involves the activation of a cyclic
      nucleotide-gated (CNG) channel by cAMP. Previous studies identified a CNG channel
      alpha subunit (CNG2) and a beta subunit (CNG5), which when heterologously
      expressed form a channel with properties similar but not identical to those of
      native olfactory neurons. We have cloned a new type of CNG channel beta subunit
      (CNG4. 3) from rat olfactory epithelium. CNG4.3 derives from the same gene as the
      rod photoreceptor beta subunit (CNG4.1) but lacks the long, glutamic acid-rich
      domain found in the N terminus of CNG4.1. Northern blot and in situ hybridization
      revealed that CNG4.3 is expressed specifically in olfactory neurons. Expression
      of CNG4.3 in human embryonic kidney 293 cells did not lead to detectable
      currents. Coexpression of CNG4.3 with CNG2 induced a current with significantly
      increased sensitivity for cAMP whereas cGMP affinity was not altered.
      Additionally, CNG4.3 weakened the outward rectification of the current in the
      presence of extracellular Ca2+, decreased the relative permeability for Ca2+, and
      enhanced the sensitivity for L-cis diltiazem. Upon coexpression of CNG2, CNG4.3,
      and CNG5, a conductance with a cAMP sensitivity greater than that of either the
      CNG2/CNG4.3 or the CNG2/CNG5 channel and near that of native olfactory channel
      was observed. Our data suggest that CNG4.3 forms a subunit of the native
      olfactory CNG channel. The expression of various CNG4 isoforms in retina and
      olfactory epithelium indicates that the CNG4 subunit may be necessary for normal
      function of both photoreceptor and olfactory CNG channels.

PMID- 9539803
TI  - Region-dependent dynamics of cAMP response element-binding protein
      phosphorylation in the basal ganglia.
AB  - The cAMP response element-binding protein (CREB) is an activity-dependent
      transcription factor that is involved in neural plasticity. The kinetics of CREB
      phosphorylation have been suggested to be important for gene activation, with
      sustained phosphorylation being associated with downstream gene expression. If
      so, the duration of CREB phosphorylation might serve as an indicator for time
      sensitive plastic changes in neurons. To screen for regions potentially involved
      in dopamine-mediated plasticity in the basal ganglia, we used organotypic slice
      cultures to study the patterns of dopamine- and calcium-mediated CREB
      phosphorylation in the major subdivisions of the striatum. Different durations of
      CREB phosphorylation were evoked in the dorsal and ventral striatum by activation
      of dopamine D1-class receptors. The same D1 stimulus elicited (i) transient
      phosphorylation (</=15 min) in the matrix of the dorsal striatum; (ii) sustained
      phosphorylation (</=2 hr) in limbic-related structures including striosomes, the
      nucleus accumbens, the fundus striati, and the bed nucleus of the stria
      terminalis; and (iii) prolonged phosphorylation (up to 4 hr or more) in cellular
      islands in the olfactory tubercle. Elevation of Ca2+ influx by stimulation of L
      type Ca2+ channels, NMDA, or KCl induced strong CREB phosphorylation in the
      dorsal striatum but not in the olfactory tubercle. These findings differentiate
      the response of CREB to dopamine and calcium signals in different striatal
      regions and suggest that dopamine-mediated CREB phosphorylation is persistent in
      limbic-related regions of the neonatal basal ganglia. The downstream effects
      activated by persistent CREB phosphorylation may include time-sensitive
      neuroplasticity modulated by dopamine.

PMID- 9539804
TI  - Social stress results in altered glucocorticoid regulation and shorter survival
      in simian acquired immune deficiency syndrome.
AB  - From early in the AIDS epidemic, psychosocial stressors have been proposed as
      contributors to the variation in disease course. To test this hypothesis, rhesus
      macaques were assigned to stable or unstable social conditions and were
      inoculated with the simian immunodeficiency virus. Animals in the unstable
      condition displayed more agonism and less affiliation, shorter survival, and
      lower basal concentrations of plasma cortisol compared with stable animals. Early
      after inoculation, but before the emergence of group differences in cortisol
      levels, animals receiving social threats had higher concentrations of simian
      immunodeficiency virus RNA in plasma, and those engaging in affiliation had lower
      concentrations. The results indicate that social factors can have a significant
      impact on the course of immunodeficiency disease. Socially induced changes in
      pituitary-adrenal hormones may be one mechanism mediating this relationship.

PMID- 9539805
TI  - R-type Ca2+ currents evoke transmitter release at a rat central synapse.
AB  - Voltage-dependent Ca2+ currents evoke synaptic transmitter release. Of six types
      of Ca2+ channels, L-, N-, P-, Q-, R-, and T-type, only N- and P/Q-type channels
      have been pharmacologically identified to mediate action-potential-evoked
      transmitter release in the mammalian central nervous system. We tested whether
      Ca2+ channels other than N- and P/Q-type control transmitter release in a calyx
      type synapse of the rat medial nucleus of the trapezoid body. Simultaneous
      recordings of presynaptic Ca2+ influx and the excitatory postsynaptic current
      evoked by a single action potential were made at single synapses. The R-type
      channel, a high-voltage-activated Ca2+ channel resistant to L-, N-, and P/Q-type
      channel blockers, contributed 26% of the total Ca2+ influx during a presynaptic
      action potential. This Ca2+ current evoked transmitter release sufficiently large
      to initiate an action potential in the postsynaptic neuron. The R-type current
      controlled release with a lower efficacy than other types of Ca2+ currents.
      Activation of metabotropic glutamate receptors and gamma-aminobutyric acid type B
      receptors inhibited the R-type current. Because a significant fraction of
      presynaptic Ca2+ channels remains unidentified in many other central synapses,
      the R-type current also could contribute to evoked transmitter release in these
      synapses.

PMID- 9539807
TI  - All-or-none potentiation at CA3-CA1 synapses.
AB  - The molecular mechanisms underlying long-term potentiation in the hippocampus
      have received much attention because of the likely functional importance of
      synaptic plasticity for information storage and the development of neuronal
      connectivity. Surprisingly, it remains unclear whether activity modifies the
      strength of individual synapses in a digital (all-or-none) or analog (graded)
      manner. Here we characterize step-like all-or-none transitions from baseline
      synaptic transmission to potentiated states following protocols for inducing
      potentiation at putative single CA3-CA1 synaptic connections. Individual synapses
      appear to have all-or-none potentiation indicative of highly cooperative
      processes but different thresholds for undergoing potentiation. These results
      raise the possibility that some forms of synaptic memory may be stored in a
      digital manner in the brain.

PMID- 9539806
TI  - Developmental emergence of different forms of neuromodulation in Aplysia sensory
      neurons.
AB  - The capacity for neuromodulation and biophysical plasticity is a defining feature
      of most mature neuronal cell types. In several cases, modulation at the level of
      the individual neuron has been causally linked to changes in the functional
      output of a neuronal circuit and subsequent adaptive changes in the organism's
      behavioral responses. Understanding how such capacity for neuromodulation
      develops therefore may provide insights into the mechanisms both of neuronal
      development and learning and memory. We have examined the development of multiple
      forms of neuromodulation triggered by a common neurotransmitter, serotonin, in
      the pleural sensory neurons of Aplysia californica. We have found that multiple
      signaling cascades within a single neuron develop sequentially, with some being
      expressed only very late in development. In addition, our data suggest a model in
      which, within a single neuromodulatory pathway, the elements of the signaling
      cascade are developmentally expressed in a "retrograde" manner with the ionic
      channel that is modulated appearing early in development, functional elements in
      the second messenger cascade appearing later, and finally, coupling of the second
      messenger cascade to the serotonin receptor appearing quite late. These studies
      provide the characterization of the development of neuromodulation at the level
      of an identified cell type and offer insights into the potential roles of
      neuromodulatory processes in development and adult plasticity.

PMID- 9539808
TI  - Hypotension and inflammatory cytokine gene expression triggered by factor Xa
      nitric oxide signaling.
AB  - The signaling pathway initiated by factor Xa on vascular endothelial cells was
      investigated. Factor Xa stimulated a 5- to 10-fold increased release of nitric
      oxide (NO) in a dose-dependent reaction (0.1-2.5 microG/ml) unaffected by the
      thrombin inhibitor hirudin but abolished by active site inhibitors, tick
      anticoagulant peptide, or Glu-Gly-Arg-chloromethyl ketone. In contrast, the
      homologous clotting protease factor IXa or another endothelial cell ligand,
      fibrinogen, was ineffective. A factor Xa inter-epidermal growth factor synthetic
      peptide L (83)FTRKL(88) (G) blocking ligand binding to effector cell protease
      receptor-1 inhibited NO release by factor Xa in a dose-dependent manner, whereas
      a control scrambled peptide KFTGRLL was ineffective. Catalytically active factor
      Xa induced hypotension in rats and vasorelaxation in the isolated rat mesentery,
      which was blocked by the NO synthase inhibitor L-N(G)-nitroarginine methyl ester
      (L-NAME) but not by D-NAME. Factor Xa/NO signaling also produced a dose-dependent
      endothelial cell release of interleukin 6 (range 0.55-3.1 ng/ml) in a reaction
      inhibited by L-NAME and by the inter-epidermal growth factor peptide Leu(83)
      Leu(88) but unaffected by hirudin. Maximal induction of interleukin 6 mRNA
      required a brief, 30-min stimulation with factor Xa, unaffected by subsequent
      addition of tissue factor pathway inhibitor. These data suggest that factor Xa
      induced NO release modulates endothelial cell-dependent vasorelaxation and
      cytokine gene expression. This pathway requiring factor Xa binding to effector
      cell protease receptor-1 and a secondary step of ligand-dependent proteolysis may
      preserve an anti-thrombotic phenotype of endothelium but also trigger acute phase
      responses during activation of coagulation in vivo.

PMID- 9539809
TI  - Stimulation of renin secretion by nitric oxide is mediated by phosphodiesterase
      3.
AB  - This study aimed to characterize the cellular pathways along which nitric oxide
      (NO) stimulates renin secretion from the kidney. Using the isolated perfused rat
      kidney model we found that renin secretion stimulated 4- to 8-fold by low
      perfusion pressure (40 mmHg), by macula densa inhibition (100 micromol/liter of
      bumetanide), and by adenylate cyclase activation (3 nmol/liter of isoproterenol)
      was markedly attenuated by the NO synthase inhibitor nitro-L-arginine methyl
      ester (L-Name) (1 mM) and that the inhibition by L-Name was compensated by the NO
      donor sodium nitroprusside (SNP) (10 micromol/liter). Similarly, inhibition of
      cAMP degradation by blockade of phosphodiesterase 1 (PDE-1) (20 micromol/liter of
      8-methoxymethyl-1-methyl-3-(2-methylpropyl)xanthine) or of PDE-4 (20
      micromol/liter of rolipram) caused a 3- to 4-fold stimulation of renin secretion
      that was attenuated by L-Name and that was even overcompensated by sodium
      nitroprusside. Inhibition of PDE-3 by 20 micromol/liter of milrinone or by 200
      nmol/liter of trequinsin caused a 5- to 6-fold stimulation of renin secretion
      that was slightly enhanced by NO synthase inhibition and moderately attenuated by
      NO donation. Because PDE-3 is a cGMP-inhibited cAMP-PDE the role of endogenous
      cGMP for the effects of NO was examined by the use of the specific guanylate
      cyclase inhibitor 1-H-(1,2,4)oxodiazolo(4,3a)quinoxalin-1-one (20 micromol). In
      the presence of 1H-[1,2,4]oxodiazolo[4,3-a]quinoxalin-1-one the effect of NO on
      renin secretion was abolished, whereas PDE-3 inhibitors exerted their normal
      effects. These findings suggest that PDE-3 plays a major role for the cAMP
      control of renin secretion. Our findings are compatible with the idea that the
      stimulatory effects of endogenous and exogenous NO on renin secretion are
      mediated by a cGMP-induced inhibition of cAMP degradation.

PMID- 9539810
TI  - Cardiac arrest in rodents: maximal duration compatible with a recovery of
      neuronal activity.
AB  - We report here that during a permanent cardiac arrest, rodent brain tissue is
      "physiologically" preserved in situ in a particular quiescent state. This state
      is characterized by the absence of electrical activity and by a critical period
      of 5-6 hr during which brain tissue can be reactivated upon restoration of a
      simple energy (glucose/oxygen) supply. In rat brain slices prepared 1-6 hr after
      cardiac arrest and maintained in vitro for several hours, cells with normal
      morphological features, intrinsic membrane properties, and spontaneous synaptic
      activity were recorded from various brain regions. In addition to functional
      membrane channels, these neurons expressed mRNA, as revealed by single-cell
      reverse transcription-PCR, and could synthesize proteins de novo. Slices prepared
      after longer delays did not recover. In a guinea pig isolated whole-brain
      preparation that was cannulated and perfused with oxygenated saline 1-2 hr after
      cardiac arrest, cell activity and functional long-range synaptic connections
      could be restored although the electroencephalogram remained isoelectric.
      Perfusion of the isolated brain with the gamma-aminobutyric acid A receptor
      antagonist picrotoxin, however, could induce self-sustained temporal lobe
      epilepsy. Thus, in rodents, the duration of cardiac arrest compatible with a
      short-term recovery of neuronal activity is much longer than previously expected.
      The analysis of the parameters that regulate this duration may bring new insights
      into the prevention of postischemic damages.

PMID- 9539811
TI  - Xanthine oxidase activity associated with arterial blood pressure in
      spontaneously hypertensive rats.
AB  - Recent evidence in vivo indicates that spontaneously hypertensive rats (SHR)
      exhibit an increase in oxyradical production in and around microvascular
      endothelium. This study is aimed to examine whether xanthine oxidase plays a role
      in overproduction of oxidants and thereby may contribute to hypertensive states
      as a consequence of the increasing microvascular tone. The xanthine oxidase
      activity in SHR was inhibited by dietary supplement of tungsten (0.7 g/kg) that
      depletes molybdenum as a cofactor for the enzyme activity as well as by
      administration of (-)BOF4272 [(-)-8-(3-methoxy-4
      phenylsulfinylphenyl)pyrazolo(1,5-alpha)-1,3, 5-triazine-4-monohydrate], a
      synthetic inhibitor of the enzyme. The characteristic elevation of mean arterial
      pressure in SHR was normalized by the tungsten diet, whereas Wistar Koto (WKY)
      rats displayed no significant alteration in the pressure. Multifunctional
      intravital videomicroscopy in mesentery microvessels with hydroethidine, an
      oxidant-sensitive fluoroprobe, showed that SHR endothelium exhibited
      overproduction of oxyradicals that coincided with the elevated arteriolar tone as
      compared with WKY rats. The tungsten diet significantly repressed these changes
      toward the levels observed in WKY rats. The activity of oxyradical-producing form
      of xanthine oxidase in the mesenteric tissue of SHR was approximately 3-fold
      greater than that of WKY rats, and pretreatment with the tungsten diet eliminated
      detectable levels of the enzyme activity. The inhibitory effects of the tungsten
      diet on the increasing blood pressure and arteriolar tone in SHR were also
      reproducible by administration of (-)BOF4272. These results suggest that xanthine
      oxidase accounts for a putative source of oxyradical generation that is
      associated with an increasing arteriolar tone in this form of hypertension.

PMID- 9539812
TI  - Role of substance P and the neurokinin 1 receptor in acute pancreatitis and
      pancreatitis-associated lung injury.
AB  - Substance P, acting via the neurokinin 1 receptor (NK1R), plays an important role
      in mediating a variety of inflammatory processes. However, its role in acute
      pancreatitis has not been previously described. We have found that, in normal
      mice, substance P levels in the pancreas and pancreatic acinar cell expression of
      NK1R are both increased during secretagogue-induced experimental pancreatitis. To
      evaluate the role of substance P, pancreatitis was induced in mice that
      genetically lack NK1R by administration of 12 hourly injections of a
      supramaximally stimulating dose of the secretagogue caerulein. During
      pancreatitis, the magnitude of hyperamylasemia, hyperlipasemia, neutrophil
      sequestration in the pancreas, and pancreatic acinar cell necrosis were
      significantly reduced in NK1R-/- mice when compared with wild-type NK1R+/+
      animals. Similarly, pancreatitis-associated lung injury, as characterized by
      intrapulmonary sequestration of neutrophils and increased pulmonary microvascular
      permeability, was reduced in NK1R-/- animals. These effects of NK1R deletion
      indicate that substance P, acting via NK1R, plays an important proinflammatory
      role in regulating the severity of acute pancreatitis and pancreatitis-associated
      lung injury.

PMID- 9539813
TI  - Recessive and dominant mutations in the ethylene biosynthetic gene ACS5 of
      Arabidopsis confer cytokinin insensitivity and ethylene overproduction,
      respectively.
AB  - We identified a set of cytokinin-insensitive mutants by using a screen based on
      the ethylene-mediated triple response observed after treatment with low levels of
      cytokinins. One group of these mutants disrupts ACS5, a member of the Arabidopsis
      gene family that encodes 1-aminocyclopropane-1-carboxylate synthase, the first
      enzyme in ethylene biosynthesis. The ACS5 isoform is mainly responsible for the
      sustained rise in ethylene biosynthesis observed in response to low levels of
      cytokinin and appears to be regulated primarily by a posttranscriptional
      mechanism. Furthermore, the dominant ethylene-overproducing mutant eto2 was found
      to be the result of an alteration of the carboxy terminus of ACS5, suggesting
      that this domain acts as a negative regulator of ACS5 function.

PMID- 9539814
TI  - Architectural specificity in chromatin structure at the TATA box in vivo:
      nucleosome displacement upon beta-phaseolin gene activation.
AB  - Extensive studies of the beta-phaseolin (phas) gene in transgenic tobacco have
      shown that it is highly active during seed embryogenesis but is completely silent
      in leaf and other vegetative tissues. In vivo footprinting revealed that the lack
      of even basal transcriptional activity in vegetative tissues is associated with
      the presence of a nucleosome that is rotationally positioned with base pair
      precision over three phased TATA boxes present in the phas promoter. Positioning
      is sequence-dependent because an identical rotational setting is obtained upon
      nucleosome reconstitution in vitro. A comparison of DNase I and dimethyl sulfate
      footprints in vivo and in vitro strongly suggests that this repressive chromatin
      architecture is remodeled concomitant with gene activation in the developing
      seed. This leads to the disruption of histone-mediated DNA wrapping and the
      assembly of the TATA boxes into a transcriptionally competent nucleoprotein
      complex.

PMID- 9539815
TI  - Membrane voltage initiates Ca2+ waves and potentiates Ca2+ increases with
      abscisic acid in stomatal guard cells.
AB  - In higher plants changes and oscillations in cytosolic free Ca2+ concentration
      ([Ca2+]i) are central to hormonal physiology, including that of abscisic acid
      (ABA), which signals conditions of water stress and alters ion channel activities
      in guard cells of higher-plant leaves. Such changes in [Ca2+]i are thought to
      encode for cellular responses to different stimuli, but their origins and
      functions are poorly understood. Because transients and oscillations in membrane
      voltage also occur in guard cells and are elicited by hormones, including ABA, we
      suspected a coupling of [Ca2+]i to voltage and its interaction with ABA. We
      recorded [Ca2+]i by Fura2 fluorescence ratio imaging and photometry while
      bringing membrane voltage under experimental control with a two-electrode voltage
      clamp in intact Vicia guard cells. Free-running oscillations between voltages
      near -50 mV and -200 mV were associated with oscillations in [Ca2+]i, and, under
      voltage clamp, equivalent membrane hyperpolarizations caused [Ca2+]i to increase,
      often in excess of 1 microM, from resting values near 100 nM. Image analysis
      showed that the voltage stimulus evoked a wave of high [Ca2+]i that spread
      centripetally from the peripheral cytoplasm within 5-10 s and relaxed over 40-60
      s thereafter. The [Ca2+]i increases showed a voltage threshold near -120 mV and
      were sensitive to external Ca2+ concentration. Substituting Mn2+ for Ca2+ to
      quench Fura2 fluorescence showed that membrane hyperpolarization triggered a
      divalent influx. ABA affected the voltage threshold for the [Ca2+]i rise, its
      amplitude, and its duration. In turn, membrane voltage determined the ability of
      ABA to raise [Ca2+]i. These results demonstrate a capacity for voltage to evoke
      [Ca2+]i increases, they point to a dual interaction with ABA in triggering and
      propagating [Ca2+]i increases, and they implicate a role for voltage in
      "conditioning" [Ca2+]i signals that regulate ion channels for stomatal function.

PMID- 9539816
TI  - Sucrose is a signal molecule in assimilate partitioning.
AB  - The proton-sucrose symporter mediates the key transport step in the resource
      distribution system that allows many plants to function as multicellular
      organisms. In the results reported here, we identify sucrose as a signaling
      molecule in a previously undescribed signal-transduction pathway that regulates
      the symporter. Sucrose symporter activity declined in plasma membrane vesicles
      isolated from leaves fed exogenous sucrose via the xylem transpiration stream.
      Symporter activity dropped to 35-50% of water controls when the leaves were fed
      100 mM sucrose and to 20-25% of controls with 250 mM sucrose. In contrast,
      alanine symporter and glucose transporter activities did not change in response
      to sucrose treatments. Decreased sucrose symporter activity was detectable after
      8 h and reached a maximum by 24 h. Kinetic analysis of transport activity showed
      a decrease in Vmax. RNA gel blot analysis revealed a decrease in symporter
      message levels, suggesting a drop in transcriptional activity or a decrease in
      mRNA stability. Control experiments showed that these responses were not the
      result of changing osmotic conditions. Equal molar concentrations of hexoses did
      not elicit the response, and mannoheptulose, a hexokinase inhibitor, did not
      block the sucrose effect. These data are consistent with a sucrose-specific
      response pathway that is not mediated by hexokinase as the sugar sensor. Sucrose
      dependent changes in the sucrose symporter were reversible, suggesting this
      sucrose-sensing pathway can modulate transport activity as a function of changing
      sucrose concentrations in the leaf. These results demonstrate the existence of a
      signaling pathway that can control assimilate partitioning at the level of phloem
      translocation.

PMID- 9539817
TI  - [Dobutamine stress echocardiography; a tool in maturity].

PMID- 9539818
TI  - [Dobutamine stress echocardiography; a monocentric experience on 600 consecutive
      patients. Effect of age].
AB  - The increasing indications of dobutamine stress echo in the investigation of
      myocardial ischaemia, viability and evaluation of the prognosis of coronary
      artery disease has made this technique a tool of everyday clinical practice. The
      authors reviewed the results of 600 investigations in consecutive unselected
      including patients aged over 75. No significant difference was observed with
      respect to the causes of interruption of the test between patients aged less than
      75 (521 patients) and those older than 75 (79 patients). Attaining the target
      theoretical maximal heart rate was the commonest reason for stopping the test (47
      and 48% respectively). Ventricular arrhythmias were not more common (12 and 10%
      respectively). Twelve cases of ventricular tachycardia were observed, 8 of which
      were non-sustained; 9 led to interruption of the test. No cases of ventricular
      fibrillation were observed. A previous history of cardiac arrhythmias was not
      associated with a higher frequency of arrhythmia during the test (8% in those
      with a previous history, 4% in those patients without). Supraventricular
      arrhythmias were significantly more common in patients over 75 years of age (15
      versus 8%, p = 0.046). Dobutamine stress echocardiography' is feasible in a
      population of unselected patients, including those over 75. Therefore, age does
      not represent a limitation to the extension of this investigation.

PMID- 9539819
TI  - [Quantification of mitral regurgitation by cine-MRI. Comparison with
      transesophageal echocardiography in 45 patients].
AB  - Cine-MRI demonstrates the presence of mitral regurgitation by a signal void. This
      study was undertaken to assess the value of this method for quantification of
      mitral regurgitation in a population not excluding either patients with mitral
      valve prostheses or those with atrial fibrillation. The subjects included had a
      mean age of 59 years and were referred for transoesophageal echocardiography,
      either for assessment of valvular heart disease (38 patients), or for detection
      of atrial thrombosis before external electrical cardioversion (7 patients). Eight
      patients had mitral valve prostheses and 19 were in atrial fibrillation. Cine-MRI
      was performed within 12 days of the transoesophageal echocardiography study with
      a 1.5 tesla magnet, using a sequence of gradient echo in 3 parallel planes in the
      4 chamber view. The regurgitation was quantified by MRI from the extension of the
      signal void in the left atrium. The transoesophageal Doppler echocardiographic
      criteria were the width of the regurgitant jet at its origin, the intensity of
      the regurgitation signal recorded by continuous wave Doppler and the extension of
      the jet within the left atrium. The quantification by degrees 1 to 4 did not
      differ by more than 1 degree between the 2 techniques in 43 of the 45 patients.
      Out of 4 left atrial thrombus detected by transoesophageal echocardiography, only
      1 was visible by MRI. The authors concluded that quantification of mitral
      regurgitation by cine-MRI provides similar results to those obtained by
      transoesophageal echocardiography and that the correlation remains valid in cases
      of atrial fibrillation. However, Doppler echocardiography provides further
      valuable information for the clinician.

PMID- 9539820
TI  - [Mobile thrombi of the right heart in pulmonary embolism].
AB  - Systematic transthoracic echocardiography in all cases of pulmonary embolism may
      demonstrate right heart thrombi. The results of this monocentric series of 28
      consecutive cases observed between 1987 and 1996 were analysed. Twenty-four
      patients were in NYHA Class IV: thirteen were in cardiogenic shock.
      Echocardiographic signs of acute cor pulmonale were usually observed: 96.3% of
      patients had right ventricular dilatation, 85.2% paradoxical interventricular
      septal motion, 88.9% pulmonary hypertension. The thrombus was typical serpentine
      (27/28 cases) arising from the lower limb veins. Passage into the left heart
      chambers through a patent foramen ovale was observed in 3 cases. Pulmonary
      embolism was confirmed in all cases. This is an extreme therapeutic emergency and
      13 patients (46.4%) died despite treatment: surgery (7/16), thrombolysis (2/5),
      heparin (3/4) or interventional radiology (1/3). After the acute phase, the
      prognosis was generally good, as demonstrated by the 100% survival rate at 28.6
      +/- 25 months. This study confirms the gravity of mobile right heart thrombi in
      pulmonary embolism. The diagnosis is echocardiographic. No significant difference
      in mortality was observed between the different therapeutic approaches used in
      this series. The echocardiographic finding of these thrombi is a traditional
      indication for emergency surgical embolectomy. Thrombolysis is rapid and readily
      available and seems to provide promising results alone or before surgery. In
      patients with contraindications to thrombolysis, interventional radiology or
      simple heparin therapy may be proposed.

PMID- 9539821
TI  - [Analysis of heart rate variability before and at the moment of cardiac death].
AB  - The study of heart rate variability is a new means of assessing autonomic nervous
      system function and the risks of cardiac and sudden death in patients with
      advandec cardiac disease. The aim of this study was to analyse changes in heart
      rate variability in the hours preceding cardiac death and just before its
      occurrence. Seventeen subjects aged 78.5 +/- 10 years, with advanced cardiac
      disease responsible for a reduction of left ventricular ejection fraction below
      40%, died during Holter ECG recording. Ten died of ventricular fibrillation, 5 of
      bradycardia and 2 of non-rhythmic causes. General analysis of heart rate
      variability showed a decrease in all but 1 patient, the average standard
      deviation of normal RR intervals in subjects in sinus rhythm being 53 +/- 14 msec
      and the fractioned spectral power (low frequency/high frequency power) being 1 +/
      .07. The change in heart rate variability did not allow prediction of the
      mechanism of death: the mean heart rate only increased before death in 3 of the
      patients with an ischaemic component in the hours before death, the indices of
      vagal tone were very low in the majority of patients and, just before death, a
      disequilibrium between the spectral powers with a sudden increase in LF/HF ratio
      of 10 of the 17 patients, irrespective of the cause of death, appeared. In
      conclusion, a decrease in heart rate variability was observed in all cases but
      did not predict the mechanism of death. Just before death occurred, some
      patients, especially those with acute ischaemia, showed a sudden change in the
      indices of heart rate variability indicating a terminal vaso-sympathetic
      disequilibrium.

PMID- 9539822
TI  - [Characteristics of patients hospitalized for myocardial infarction in France
      with respect to left ventricular dysfunction. Results of the USIK study].
AB  - Patients admitted in coronary care units, in november 1995, for confirmed acute
      myocardial infarction within 48 hours of symptoms onset were included in this
      study. The choice of measurement of left ventricular ejection fraction (LVEF) was
      left to the physician in charge. Only investigations performed within the first 8
      days were taken into consideration. In cases with multiple investigations, the
      following order of preference was applied: a) angiographic LVEF, b) isotopic
      LVEF, c) echocardiographic ejection fraction by Simpson's method, d)
      echocardiographic ejection fraction by Berning's method, e) semi-quantitative
      visual echocardiographic evaluation. 2563 patients were included (1827 males and
      736 females, mean age 67 years). A quantitative evaluation of LVEF was obtained
      in 1477 patients (57%) whereas 2 053 patients (80%) underwent at least a semi
      quantitative evaluation. The average LVEF was 50% and 17% of patients had an
      ejection fraction < or = 35%. Patients with LVEF < or = 35% were older, less
      likely males, non smokers and diabetics. Prior heart failure, previous myocardial
      infarction and anterior location in infarction were more frequent. Heart failure
      was more frequent in patients with LVEF < or = 35% (75 vs 23%, p < 0.001). One
      hundred and ninety-seven patients (7.7%) died in the five first days following
      the onset of symptoms. A left ventricular ejection fraction < or = 35% multiplied
      the risk of death by 8.1 (Confidence interval: 5.7-11.4, p < 0.001). The presence
      of clinical heart failure increased the risk even more.

PMID- 9539823
TI  - [Local progression of atherosclerosis after optimal directional atherectomy.
      Endocoronary ultrasonography of 17 patients].
AB  - In vivo endovascular ultrasonography has confirmed the extension of atheroma to
      angiographically normal segments. The authors set out to determine by
      endocoronary ultrasonography if the introduction of the atherotome changed the
      intimal thickness 20 mm proximal and distal to the site treated. The area
      circumscribed by the external elastic layer (EEL) and the surface area of the
      lumen was measured in 17 patients: 1) before atherectomy; 2) after atherectomy;
      3) at control 6 months later. Atherectomy immediately increased the luminal area
      at the site dilated from 1.9 + 0.9 to 8.1 +/- 2mm (p < 0.001). At the proximal
      segment, the surface area of the lumen was unchanged (mean + 0.6 +/- 1.5 mm2; p =
      0.13). Similarly the procedure did not change the surface circumscribed by the
      EEL (mean + 0.8 +/- 3.2 mm2; p = 0.32) in this zone. The same results were
      observed at the distal site. At 6 months, the areas under the EEL and those of
      the lumen were unchanged at the unoperated sites. The mean of the differences (+/
      1 SD) for the area under the EEL was respectively -0.2 +/- 1.5 mm2 proximally
      and +0.7 +/- 2.5 mm2 distally. The means for the luminal area were 0.2 +/- 1 mm2
      proximally and -0.01 +/- 1.1 mm2; distally. At the site of atherectomy, the
      luminal surface increased (+2.0 +/- 2.6 mm2; p < 0.01) as did the area under the
      EEL (+2.0 +/- 3.5 mm2; p < 0.05). This preliminary series shows no significant
      progression of atherosclerosis at the sites not affected by atherectomy.

PMID- 9539824
TI  - [Contribution of MRI in the evaluation of ischemic heart diseases].
AB  - The high spatial and temporal resolution of MRI provides accurate identification
      of left ventricular endocardial and epicardial contours. Cine-MRI allows reliable
      and reproducible measurements of end-systolic and end-diastolic volumes, ejection
      fraction and left ventricular mass. These measurements are not based on any
      geometrical hypothesis and so remain valid in presence of ventricular deformation
      as observed after myocardial infarctions. The value of cine-MRI has been
      demonstrated in ischaemic heart disease for the study of regional left
      ventricular function, by analysis of left ventricular segmental function and
      systolic thickening of the myocardial walls. Cine-MRI may also be performed
      during pharmacological stress. In coronary patients without ventricular
      dysfunction at rest, stress cine-MRI enables detection of segmental wall motion
      abnormalities or reduction of systolic thickening in potentially ischaemic
      territories. Cine-MRI may contribute to be study of myocardial viability.
      Regional myocardial perfusion may also be assessed using the rapid sequences of
      imaging and contrast agents opacifying the intravascular compartment. In coronary
      patient, underperfused regions may there by be detected. The most rapid imaging
      techniques enable visualisation of the proximal segments of the coronary arteries
      and the measurement of blood velocity in the coronary arteries and the
      calculation of coronary reserve. Simultaneous analysis under basal conditions and
      after pharmacological stress of global and segmental left ventricular function
      and of myocardial perfusion, associated with the possibility of imaging the
      proximal coronary arteries and of measuring the velocity of coronary flow, makes
      MRI a complete non-invasive method of evaluating patients with ischaemic heart
      disease.

PMID- 9539825
TI  - [Epidemiology of myocardial infarction in France. Regional specificities].
AB  - A national epidemiological study undertaken in November 1995 recensed the data of
      2563 patients admitted to 373 Intensive Care Units for acute myocardial
      infarction. There were 1827 men and 736 women with an average age of 67 years.
      Seventeen per cent of patients had left ventricular ejection fration (LVEF) < or
      = 35%. The mortality rate at 5 days was 7.7%. Clinical heart failure (Killip > 1)
      was observed in 34.4% of patients. 63% of patients were admitted before the 6th
      hour. Forty-six per cent of patients underwent early revascularisation by
      thrombolysis and/or angioplasty. The most widely used drugs in the first 5 days
      were heparin (96%), aspirin (89%), betablockers (65%), and angiotension
      converting enzyme inhibitors (46%). The influence of region on the demographical
      features, morbidity, mortality and therapeutic practice was studied. France was
      divided into 6 regions. In the Centre, the patients were older, with increased
      morbidity and mortality compared with the national average. Patients in the North
      East were similar and had a higher incidence of obesity. In the Ile de France,
      patients were generally younger with a higher incidence of tobacco consumption
      and their infarcts were generally less severe. Finally, in the South East, the
      mortality was particularly low. In multivariate analysis living in this region
      was good prognostic factor whereas low LVEF (< or = 35%) and age > or = 65 years
      were poor prognostic factors. This study, for the first time in France, describes
      the clinical features of myocardial infarction admitted to the Intensive Care
      Unit with respect to criteria of severity (LVEF, Killip) and region of origin of
      the patients. Its confirms large regional variations in the severity of acute
      myocardial infarction.

PMID- 9539826
TI  - [Left ventricular reduction (Batista's technique). A new surgical option in
      dilated cardiomyopathy].
AB  - Cardiac transplantation remains the standard treatment for severe cardiomyopathy
      resistant to medical therapy. However, new techniques may help to put this off.
      Two patients with dilated cardiomyopathy were treated surgically since October
      1996, one aged 48 and the other 52. They were in NYHA Class IV and one was
      dependent on inotropic drugs. Both had relative or absolute contra-indications to
      transplantation. The left ventricular end diastolic dimensions were over 70 mm
      with mild mitral regurgitation and fractional shortening of less than 12%.
      Coronary angiography was normal. They were operated in October 1996 and January
      1997. The procedure consisted of correction of mitral regurgitation
      (annuloplasty) and of reduction of left ventricular volume by a triangular
      resection from the apese to the base of the heart. At histological examination,
      the resected myocardium measured 11 to 13 cm long and 5 to 7 cm at its base. The
      two patients were discharged from hospital after 45 and 30 days. There were no
      clinical signs of cardiac failure. Follow-up investigations showed a marked
      decrease in ventricular volumes, the end diastolic dimensions changing from 70 to
      52 mm in the first, and from 76 to 54 mm in the second patient. The corresponding
      values of fractional shortening increased from 11 to 20% and from 6 to 17%. Left
      ventricular volumes decreased from 328 mL (end diastole) and 259 mL (end systole)
      to 140 mL and 74 mL in the first case, and from 300 mL (end diastole) and 280 mL
      (end systole) to 122 mL and 83 mL respectively in the second case. The ejection
      fraction increased from 20 to 40% and from 10 to 32%. These preliminary results
      show that the theoretical advantages of this surgical technique correspond to a
      practical reality. Larger series of patients are required to determine the
      optimal indications.

PMID- 9539827
TI  - [Myocardial localization of malignant non-Hodgkin lymphoma responsive to
      chemotherapy].
AB  - Cardiac malignant non-hodgkinian lymphoma, which is usually asymptomatic, is
      observed in 15 to 25% of autopsy cases of this condition. The authors report an
      unusual case of myocardial lymphoma diagnosed during pulmonary oedema.
      Echocardiography showed left ventricular hypertrophy with increased echogenicity
      of the myocardial walls and marked decrease in left ventricular ejection
      fraction. Myocardial biopsy confirmed the diagnosis of a high grade malignant
      lymphoma. The disease responded to chemotherapy. Early diagnosis of myocardial
      involvement of a lymphoma, presenting with non-specific electrocardiographic
      changes, requires investigation by histological study of a myocardial biopsy.
      This invasive technique is justified because of its therapeutic implications.

PMID- 9539828
TI  - [Paradoxical embolism and thrombosis trapped in the foramen ovale. Role of
      transesophageal echocardiography].
AB  - The authors report a case of paradoxical embolism presenting with syncope and a
      transient cerebrovascular accident. A large thrombus was observed entrapped in
      the foramen ovale during transthoracic echocardiography and confirmed at
      transoesophageal echocardiography. Despite the recent cerebrovascular event
      surgery was successfully performed. This clinical situation, and a review of the
      literature illustrate the diagnostic value of transoesophageal echocardiography,
      the finding of an intra-atrial thrombus being a possible surgical indication when
      the clinical context is favourable.

PMID- 9539829
TI  - [Primary cardiac sarcoma treated by orthoptic cardiac transplantation. Apropos of
      a case].
AB  - The authors report a new case of cardiac sarcoma treated by cardiac
      transplantation. This treatment has been proposed for these malignant tumours of
      poor prognosis when simple excision is impossible, with variable results. This
      patient is in good general condition 20 months after transplantation.
      Transplantation is a therapeutic procedure which should be considered in
      malignant tumours limited to the heart.

PMID- 9539830
TI  - [Intrinsic sinus node dysfunction in adolescence during anorexia nervosa].
AB  - A seventeen year old girl with anorexia nervosa (32 kg; 165 cm) was admitted as
      an emergency after syncope with severe bradycardia resistant to atropine
      monitored over a one week period. Autonomic blockade confirmed the intrinsic
      character of the sinus node dysfunction with chronotropic incompetence on
      exercise. Secondarily, a Mobitz I second degree AVB was observed. A DDDR
      pacemaker was implanted with an excellent functional result. With a one year
      follow-up, the bradycardia persists but body weight has increased. The authors
      discuss the physiopathology of this case: in the literature, the classical
      bradycardia of anorexia nervosa is sensitive to vagolytic drugs and only
      exceptionally as intense as in this patient. Sinus node dysfunction is very rare
      in the young in the absence of congenital heart disease. It is possible that the
      bradycardia had become chronic in this case.

PMID- 9539832
TI  - [Total coronary occlusions: a new challenge for stents].

PMID- 9539831
TI  - [Apropos of the role of rehabilitation medicine].

PMID- 9539833
TI  - [Recanalization of complete coronary occlusions followed by STENT implantation.
      An angiographic study after 6 months].
AB  - The restenosis and reocclusion rate after coronary recanalization by conventional
      angioplasty are high. The role of stent implantation in this context is unknown.
      The authors assessed a group of 49 patients who underwent implantation of one or
      more stent after a recanalization procedure by angiography at 6 months. The
      restenosis rate assessed by quantitative angiography was 24%; no cases of
      reocclusion were observed. These angiographic results were accompanied with a
      significant improvement of the anginal symptoms (p < 0.01). These results suggest
      that stent implantation following recanalization of a coronary occlusion may be
      beneficial on the restenosis and reocclusion rates and anginal symptoms. However,
      they should be confirmed by randomised study. It would also be important to
      analyse the impact of this procedure on the outcome of left ventricular function.

PMID- 9539834
TI  - [Coronary angiography by left radial approach. A bi-center prospective pilot
      study].
AB  - The aim of this study was to assess prospectively the feasibility, safety and
      quality of coronary angiography performed by a left radial arterial approach. The
      investigation was performed under local anesthesia with a Lidocaine gel using
      Judkins 5f catheter. A bolus of heparin was injected intravenously at the start
      of the procedure (no heparin in phase 0.2 to 3.000 IU during phase 1 and 5.000 IU
      in phase 2). Between March 1994 and January 1996, after exclusion of 108 patients
      (15.1%) mainly because of an abnormal Allen test, coronary angiography was
      carried out in 540 patients aged 58.4 +/- 11.7 years, 85% of whom were men. The
      failure rate was 8%. The quality of opacification of the left coronary artery
      (scale 1 to 3) was 2.91 +/- 0.27 and of the right coronary artery was 2.96 +/-
      0.18. There were no complications during the procedure. Analysis of the learning
      curve showed a failure rate decreasing to less than 5% after 60
      procedures/operator. In the last 100 procedures, the failure rate fell to 3%, the
      canulation time was 2.2 +/- 2.5 min, the duration of fluoroscopy was 6.5 +/- 3.9
      min and the duration of the procedure was 17.5 +/- 4.7 min (14.7 +/- 3.8 min, p <
      0.01, by the femoral approach). Clinical and Doppler ultrasonographic follow-up
      revealed one in-hospital complication (a spontaneously regressive compressive
      haematoma). No clinical complications were observed at 3 months. Doppler
      ultrasonography showed the radial artery occlusion rate to be 71% in phase 0.32%
      in phase 1 and 3.2% in phase 2 (p < 0.0001). These results show that the left
      radial arterial approach for coronary angiography is safe and effective but
      requires a period of training. A 5.000 IU dose of heparin limits the risk of
      radial artery occlusion to 3%. The absence of complications in this large series
      which included the training period and the patient comfort suggest that this
      technique may be an excellent alternative to the femoral approach and especially
      the brachial approach when the Allen test is normal.

PMID- 9539835
TI  - [Surgical treatment of fixed subvalvular aortic stenosis. Immediate and long-term
      hemodynamic results].
AB  - Forty patients operated on for fixed subvalvular aortic stenosis underwent
      cardiac catheterization preoperatively, immediately after coming off
      cardiopulmonary bypass and at long-term (1 to 14 years later, average 7 +/- 3.9
      years). The age range was 3 to 50 years (average 15 +/- 12 years) with 27 (68%)
      aged under 18 years. Twenty-seven patients were male. The stenosis was the thin
      membranous type in 29, the fibromuscular collar type in 5, the tunnel type in 5
      others and related to supernumerary mitral tissue in the remaining patient.
      Significant other pathology was associated in 13 cases. In addition to excision
      of the membrane or the fibromuscular ring, the surgeons performed myotomy in 6
      cases, myomectomy in 12 cases, large resection of muscular and fibrous tissue in
      tunnels, and aortic valve replacement in 3 cases. There was no operative
      fatality. Permanent cardiac pacing was required in 1 patient for complete
      atrioventricular block. The peak systolic pressure gradient fell from 87 +/- 32
      to 31 +/- 10 mmHg (p < 0.0001) at the immediate control: it remained > 30 and
      even 50 mmHg in 3 patients (7.5%), 2 of whom had tunnel types and the other the
      supernumerary mitral tissue. The gradient increased in the long-term to 42 +/- 11
      mmHg, 1 patient with a membrane developed a gradient of 40 mmHg and 4 others
      (10%) developed a gradient > 50 mmHg (3 tunnels and 1 membrane). The 5 patients
      with tunnel types either had a residual stenosis or restenosis and underwent
      aorto-ventriculoplasty by Konno's procedure 1 to 8 years later. This operation
      should be the procedure of first intention, even in small children: the large
      resection is only acceptable when it cannot be performed or when aortic ring
      hypoplasia is mild. There is no residual stenosis and restenosis is rare (2.5%)
      in the membranous and fibromuscular types, probably because of the widespread use
      of myotomy and myomectomy. In the absence of severe associated malformations,
      surgery in only justified when peak systolic pressure gradients are > or = 50
      mmHg.

PMID- 9539836
TI  - [Long-term reproducibility of programmed atrial stimulation].
AB  - Programmed atrial stimulation is a technique increasingly used to assess
      different pathologies but the reproducibility of the results is totally unknown.
      The aim of this study was to determine its reproducibility. Two
      electrophysiological studies were undertaken without antiarrhythmic therapy in an
      interval of one to three months (average 18 months) in 48 patients. The
      programmed atrial stimulation used 1 and 2 extrastimuli delivered in sinus rhythm
      and then three paced rhythms (sinus cycle -10%, 600 ms, 400 ms). Twenty-one
      patients had documented atrial arrhythmias (atrial fibrillation n = 13, flutter n
      = 3 or tachycardia n = 5) (group 1) and the 27 other patients had no spontaneous
      arrhythmias (group II). In group I, clinical tachycardial was reproduced in 18
      patients during the initial stimulation procedure. During the second
      investigation, 17 remained inducible and in the 3 in whom stimulation was
      negative, it remained so in 2 of the cases. The reproducibility was therefore
      90%. In group II, 12 patients had inducible sustained (for over 1 minute)
      tachycardia during the first procedure (44%) but this only remained inducible in
      6 patients. In the other 15 subjects, stimulation was negative during the first
      procedure but 7 of them had inducible tachycardial during the second procedure.
      The reproducibility of the technique was therefore only of 52%. The authors
      conclude that the reproducibility of programmed atrial stimulation in patients
      with documented spontaneous paroxysmal arrhythmias is excellent. However, the
      reproducibility is mediocre in subjects without spontaneous arrhythmias and the
      induction of tachycardial in this group of patients should be interpreted with
      caution given the variability of the response to programmed atrial stimulation.

PMID- 9539837
TI  - [An experience of lipoprotein (a) dosage in a Moroccan population of 184
      subjects].
AB  - One hundred and eighty-four patients underwent complete lipid analysis (total
      cholesterol, HDL and LDL cholesterol, triglycerides, apolipoproteins A1 and B,
      lipoprotein (a)) and coronary angiography, in order to evaluate the discriminant
      value of the lipoprotein (a). Subjects with non-significant coronary stenoses (<
      50% of the lumen) were used as a control group (n = 84). The others were
      considered to be pathological. The total cholesterol, HDL cholesterol and
      triglycerides were measured by an enzymatic colorimetric method. The LDL
      cholesterol was calculated by Friedewald's formula. The apolipoprotein A1 and B
      were measured by immunoturbidimetry and the lipoprotein (a) by an Elisa. The
      results showed a relationship between the different lipid levels, especially
      between high lipoprotein (a), and the severity of the coronary disease. A
      quantitative and qualitative study showed no significant influence of the other
      risk factors on the mean lipoprotein (a) level. Gender and age had no influence.
      Therefore, the higher the lipoprotein (a) level, the greater was the coronary
      risk, independently of the other associated risk factors.

PMID- 9539838
TI  - [HIV infection and pericardial disease invasion in Africa].
AB  - The number of cases with pericardial disease has been increasing in Africa and
      particularly in Zaire, after AIDS was defined. To investigate a possible link
      between HIV infection and risen incidence of pericardial effusions, 64 patients
      randomly selected (32 HIV carriers and 32 HIV-seronegative as controls), with
      suspected pericardial disease were studied in a longitudinal trial from January
      1991 to December 1994. Central and accessory cells of immune system were measured
      in conjunction with blood screening, electrocardiogram (ECG), chest X-ray and
      cardiac ultrasound. Haematological examination included also microscopical
      examination of blood films after May-Grunwald-Giemsa staining. There were
      significant decreases of hemoglobin, CD4 cells, and basophils in HIV-seropositive
      patients. Pericardial disease was estimated 8.8% of in-hospital prevalence, in
      which 70% of cases were related to HIV infection. The HIV related pericardial
      disease had an incidence of 1.8% per year. Etiology of pericardial disease
      depends on evolution and immunodepression level; 90.5% of pericardial effusions
      related to HIV are caused by tuberculosis as shown at the second
      pericardiocenthesis.

PMID- 9539839
TI  - [Sudden death and myocardial infarction caused by thrombosis of normal coronary
      arteries: an anatomic study of 3 cases].
AB  - The anatomic lesions of two cases of sudden death (one man and one 24 years old
      woman) and of one case of rapidly fatal myocardial infarction (51 years old
      woman) are described. The coronary lesions were exclusively thrombotic with no
      associated atherosclerosis or pre-existing arterial wall change. The thrombi were
      occlusive from the outset or were constituted in successive mural stages, the
      last being occlusive and giving rise to the clinical symptoms (sudden death
      and/or myocardial infarction). Several points are discussed. The concept of
      normal coronary artery must be confirmed by anatomic examination: coronary
      angiography is not sufficient for the diagnosis of dangerous atherosclerotic
      plaques which are not particularly stenotic, eccentric, lipidic and fragile.
      Thrombogenic factors are better understood and some may play a role in these
      cases of "primary thrombosis", by they of plasma or platelet origin. The trigger
      role of spasm cannot be ignored as some of the spastic and thrombotic factors are
      similar. The preferential coronary site of these thromboses may be explained by
      constitutional changes (arterial hypolasia with narrow lumen) or acquired lesions
      (repeated arterial trauma due to shearing by the movements of the underlying left
      ventricle transmitted to the epicardial coronary arteries).

PMID- 9539840
TI  - [Myocardial Doppler tissue imaging: past, present and future].
AB  - The first Doppler spectral and pulsed tissue recordings in 1992 have given way to
      a new generation of machines which enable cardiologists to study mechanical
      events of the myocardium during the cardiac cycle by Doppler tissue imaging. This
      technique provides valuable information about regional function with quantitative
      analysis of the velocities within the myocardial wall as opposed to the global
      qualitative or semi-quantitative character of usual echocardiographic data. The
      velocity mode is the most commonly used in its three different presentations: two
      dimensional, M mode and, more traditionally, pulsed spectral modes. Two
      dimensional imaging gives a global view of the different myocardial segments and
      allows a rapid approximation of the differences of velocities between these
      segments and of myocardial wall thickness; however, it lacks the temporal
      resolution of pulsed Doppler and M mode. In addition, M mode with automatic
      programmes of velocity analysis has the advantage of providing a continuous
      spatio-temporal recording of the velocities within the myocardial wall, layer by
      layer. There is a physiological gradient of velocities highest at the endocardium
      and lowest at the epicardium. Despite the present limitations related to the
      Doppler principle itself, the technology, and the complexity of myocardial
      architecture, Doppler tissue imaging is a useful complement to information
      already available concerning pressures, flow and cardiac structures. The future
      is promising and should exceed this simple complementarity to existing ultrasound
      methods. Progress in the fields of ultrasound physics, technology,
      computerisation for acquisition of two- and three-dimensional imaging should
      provide a new physiopathological approach to the understanding of wall motion
      changes during cardiac disease.

PMID- 9539841
TI  - [Cardiovascular manifestations of Horton disease: an underestimated disease in
      cardiology].
AB  - Horton's disease is a giant cell arteritis well known for its presentation as
      temporal arteritis. It is, in fact, a systemic disease which affects over 1% of
      the general populations after 50 years of age. With the exception of the risk of
      blindness by occlusion of the ophthalmic artery, the cardiovascular
      manifestations of Horton's disease are not well known and probably underestimated
      by clinicians. The main complications are involvement of the large arteries,
      especially the thoracic aorta and subclavian and axillary arteries, the femoro
      popliteal axis and supra-aortic arterial vessels. During the initial phase of the
      disease, extension of arteritis to the carotid and vertebral arteries is of
      particular concern because of the risk of cerebral infarction. The coronary
      arteries, myocardium, pericardium of pulmonary arteries may also be affected by
      the inflammatory process. In the long-term, Horton's disease may be complicated
      by aneurysms, dissection of parietal rupture of the thoracic aorta. Treatment is
      based on steroid therapy, sometimes associated with antiplatelet agents or
      anticoagulants during the initial phase of treatment. Long-term follow-up is
      justified because of the risk of late aortic complications.

PMID- 9539842
TI  - [Paradoxes and constraints of medical progress].

PMID- 9539843
TI  - [Systemic embolism in a renal transplant patient. Echocardiographic demonstration
      of bronchial carcinoma with intracardiac invasion].
AB  - A 45 year old female renal transplant patient was admitted for subacute ischaemia
      of a lower limb. Echocardiography was performed and showed the presence of
      bronchial carcinoma with intracardiac invasion. The tumour was confirmed by
      thoracic computerised tomography and by bronchoscopy. Histological investigation
      of bronchial biopsies and of the arterial embolism extracted at surgery showed
      large cell malignant disease. The tumour partially responded to chemotherapy and
      the patient survived for 5 months. Extension of a bronchial carcinoma to the left
      atrium is a classical complication in autopsy reports but rarely a source of
      systemic embolism. Echocardiographic diagnosis of this condition is very rare.
      The incidence of malignant diseases is higher in renal transplant patients than
      in the general population but this has not been verified for bronchial carcinoma.
      Echocardiography played an essential role in this case, detecting the tumour and
      its extension, indicating a poor prognosis and guiding treatment.

PMID- 9539844
TI  - [Tricuspid endocarditis caused by Chlamydia pneumoniae. Apropos of a case].
AB  - The authors report a case of tricuspid blood culture-negative endocarditis where
      serologic investigations showed high titers of antibodies against. Chlamydia
      pneumoniae, thus suggesting its possible role as the causal agent. The treatment
      consisted of polymicrobial therapy using ciprofloxacine and doxycycline with
      favorable response thus avoiding surgical intervention. In all cases of culture
      negative endocarditis not responding to classic empiric antibiotics, Chlamydia
      infection should be suspected. Although rare cases of endocarditis due to
      Chlamydia pneumoniae have been reported in the literature, to our knowledge, this
      is the first case of isolated tricuspid valve endocarditis due to this agent to
      be reported.

PMID- 9539845
TI  - [Cardiac failure caused by renal arteriovenous fistula fifty years after
      nephrectomy. A new case and review of the literature].
AB  - Arterio-venous fistulae are rare after nephrectomy. They are the cause of
      congestive cardiac failure. This case report has two particularities: an
      exceptionally long interval, 50 years after nephrectomy, and a severe
      hypertension due to stenosis of the contra-lateral renal artery. Surgical
      treatment of these fistulae is essential and gives excellent results with rapid
      regression of the signs of cardiac failure. Percutaneous embolization is an
      alternative in patients with a high surgical risk. All previously reported cases
      are reviewed (n = 72) with their aetiological, clinical and therapeutic features.

PMID- 9539846
TI  - [Isolated left ventricular muscular diverticulum in an adult. Value of non
      invasive examinations].
AB  - The authors report a case of ventriculum in a 45 year old women investigated for
      chest pain. This was a congenital muscular left ventricular diverticulum
      confirmed by a complete imaging series including echocardiography, magnetic
      resonance imaging, angio-scintigraphy and conventional angiography. This
      diverticulum was unusual due to the fact that there was no associated congenital
      disease and that it was discovered in an adult. The authors review the literature
      and discuss the value of non-invasive imaging procedures.

PMID- 9539847
TI  - [Guidelines from the French Society of Cardiology for including non-emergency
      adult patients in a waiting list for cardiac transplantation].

PMID- 9539848
TI  - [Continuing education of general practitioners: practices, evaluations, wishes
      (1983-1996)].
AB  - Eight opinion surveys were conducted among French GPs, from 1983 through 1996.
      They showed that GPs utilize a great deal of means for updating their skills and
      knowledge. However, some means are only used for information purpose whereas
      others are high-ranked as tools for continuing training. About 3 GPs out of 10
      quote the sessions organized by a medical association aimed at continuing
      education as the most important tool for them. Medical journals are quoted by 3
      others (out of 10). One tenth quote the sessions for continuing education
      organized by hospital departments. We have to note that attendance of the
      sessions organized by continuing education associations is now subsidized by the
      Sickness Insurance National Fund. Nearly 48 percent declare they have attended
      subsidized sessions for continuing education during 1995 and 1996, and 65% among
      them find these sessions "very interesting" and appropriate to their needs. About
      22 French GPs out of 100 need additional training as concerns AIDS, drug abuse
      and the like. One tenth need additional training in the section of pains and
      cancer treatment. The third sector where training need is felt covers office
      management, administration, health economics and related topics. Continuing
      education is now compulsory to French medical doctors. In late 1996, about 43
      percent GPs deemed it "a good thing" whereas 45 found it either useless or heavy.

PMID- 9539849
TI  - [Medical education in Algeria: opinion of the students at the end of their
      curriculum].
AB  - A cohort of 120 medical stents who have nearly completed their medical training
      have been surveyed in Oran, Algeria. Most of them are not satisfied concerning
      their medical training (82%). However, they accept the conventional pattern of
      medical learning which allows little room to active participation from the
      trainees. The most appreciated scientific disciplines are cardiology for men and
      gynecology for women. In most cases, priority is given to clinical disciplines.
      Community medicine and public health are rather neglected. Similarly, at the end
      of their training, medical students' knowledge is rather tiny regarding teamwork
      or health promotion. Clearly, most of them consider themselves as care providers,
      not health builders.

PMID- 9539850
TI  - Twenty five years of cancer registration in Austria: success or failure?

PMID- 9539851
TI  - Let's clear the air of that nocturnal miasma. Cigar anyone?

PMID- 9539852
TI  - Primary aldosteronism and its variants.

PMID- 9539853
TI  - Toward the heart of ischemic preconditioning.

PMID- 9539854
TI  - Ischaemic preconditioning: present position and future directions.
AB  - Preconditioning the myocardium using short episodes of sublethal ischaemia will
      delay the onset of necrosis during a subsequent lethal ischaemic insult. This
      powerful protective adaptation of the myocyte has also been observed in other
      cell types. The potential for clinical application to benefit patients with a
      variety of pathological conditions has led to an expansion in our knowledge
      concerning the pathophysiology of ischemia-reperfusion injury and the regulatory
      mechanisms underlying cellular metabolism. We feel it is timely to assess the
      current position in this field and provide a critical appraisal to facilitate
      future research.

PMID- 9539855
TI  - Cardiovascular actions of parathyroid hormone and parathyroid hormone-related
      peptide.
AB  - Cardiovascular cells (cardiomyocytes and smooth muscle cells) are target cells
      for parathyroid hormone (PTH) and the structurally related peptide parathyroid
      hormone-related peptide (PTH-rP). PTH activates protein kinase C (PKC) of
      cardiomyocytes via a PKC activating domain previously identified on chondrocytes.
      Activation of PKC leads to hypertrophic growth and re-expression of fetal type
      proteins in cardiomyocytes. This hypertrophic effect of PTH might contribute to
      left ventricular hypertrophy in hemodialysis patients with secondary
      hyperparathyroidism. PTH-rP is expressed in cardiovascular cells (endothelial
      cells and smooth muscle cells). It does not mimic the above described actions of
      PTH but exerts effects of its own on cardiomyocytes. These effects involve
      activation of protein kinase A, via a N-terminal domain distinct from that
      identified on PTH, and activation of PKC, via a C-terminally located domain
      distinct from that found on PTH. On smooth muscle cells PTH and PTH-rP reduce the
      influence of extracellular calcium, through cAMP-dependent mechanisms. These
      inhibitory effects on voltage-dependent L-type calcium channels of smooth muscle
      cells cause vasorelaxation. Present studies concerning cardiovascular actions of
      either PTH and PTH-rP suggest that increased plasma levels of PTH and PTH-rP
      influence cardiomyocyte and smooth muscle cell physiology. It can be assumed that
      PTH-rP acts as a paracrine or autocrine modulator in heart and vessels.

PMID- 9539856
TI  - Prevalence of the prothrombin gene variant 20210 G --> A among patients with
      myocardial infarction.
AB  - OBJECTIVE: The aim of this study was to determine the prevalence of the
      prothrombin variant allele 20210A among survivors of myocardial infarction.
      BACKGROUND: The prothrombin gene variant has been identified as a novel genetic
      risk factor for venous thrombosis. However, the risk of developing arterial
      thrombosis as a result of the presence of this mutated allele is unknown.
      METHODS: The G-->A transition at position 20210 of the 3'-untranslated region was
      determined in 220 survivors of myocardial infarction and in 295 individuals from
      the general population. RESULTS: The prevalence of heterozygotes for the
      prothrombin mutated allele was 3% among patients with myocardial infarction and
      0.7% in the general population (P = 0.03). No age-related difference in the
      prevalence of the mutated allele was observed. However, for individuals over 45
      years old the prevalence among females was higher than among males (5% vs. 0%).
      CONCLUSION: These data suggest that being heterozygote for the allele variant
      20210A of the prothrombin gene could be a genetic risk factor for developing
      myocardial infarction.

PMID- 9539857
TI  - Shortening versus isometric contractions in isolated human failing and non
      failing left ventricular myocardium: dependency of external work and force on
      muscle length, heart rate and inotropic stimulation.
AB  - BACKGROUND: For reasons of simplicity, studies on isolated human myocardium have
      been conducted using exclusively isometric contractions, although positive
      inotropic interventions may differently influence force development, extent of
      shortening and myocardial work performance. We investigated human left
      ventricular failing and non-failing preparations comparing isometric versus
      isotonic, i.e., shortening contractions. RESULTS: (1) When muscle length is
      increased from 90% to 100% lMAX, peak developed force increases by 36% and 43% (p
      < 0.05) in non-failing and failing human left ventricular myocardium,
      respectively. Maximum performed work increases similarly in non-failing but
      decreases in failing myocardium. It can be shown that this discrepancy is due to
      significantly higher resting tension and does not present an insufficient
      intrinsic shortening capacity in failing myocardium. (2) When stimulation rate is
      increased from 0.5 to 2.0 Hz, isometric force increases significantly by 59% in
      non-failing and decreases by 27% in failing myocardium, whereas maximum performed
      work increases by 98% and decreases by 46%, respectively. (3) Pharmacological
      positive inotropic interventions by 7.2 mM calcium (n = 9), 3 x 10(-8) M
      isoproterenol (n = 7), 3 x 10(-8) M ouabain (n = 5), and 10(-5) M EMD 57033 (n =
      3) equally increased force development and extent of shortening: When the
      fractional effect on shortening (y) was correlated to the fractional effect on
      force (x), the following linear regression equation was obtained: y = 0.91x +
      0.26 (r = 0.86; p < 0.001). CONCLUSIONS: The data presented are of clinical and
      pharmacological importance: (1) The Frank-Starling mechanism is demonstrated to
      be existent in the failing human myocardium regarding both isometric force
      developed and maximum work performed. (2) Both force-frequency relations and--to
      a greater extent--work-frequency relations are reversed in failing human
      myocardium. (3) Independent of the pharmacological mode of action, positive
      inotropic compounds increase developed isometric force to the same extent as
      isotonic shortening and therefore potentiate maximum performed work.

PMID- 9539858
TI  - Dependence of temporal variability of ventricular recovery on myocardial
      fibrosis. Role of mechanoelectric feedback?
AB  - OBJECTIVE: The study was aimed at establishing the effect of factors involved in
      the expression of mechanoelectric feedback in the heart, such as R-R interval and
      connective tissue, on time dependent changes in ventricular recovery, as
      determined at the body surface by beat to beat variability of QRST integral maps
      (BBV-IM). METHODS: We used 15 normal 6-month-old Wistar rats. In each
      anesthetized animal, we performed a 3-minute continuous recording of 44. The
      simultaneous chest ECGs. The signals were interactively processed, 1) to
      determine mean R-R interval and R-R variability throughout the recording period
      and 2) to compute QRST integral maps from approximately 50 beats belonging to the
      end of expiration. Then BBV-IM was calculated and expressed as percentage of
      beats significantly differing from a template. At sacrifice, the amount of
      myocardial fibrosis was morphometrically evaluated. RESULTS: R-R interval was 149
      ms +/- 4, R-R interval variability 0.008 +/- 0.001 and BBV-IM 30.7% +/- 4.4.
      Myocardial fibrosis expressed as % volume of left ventricular myocardium,
      numerical density of fibrotic foci and average cross-sectional area of the foci
      was 3.0% +/- 0.4, 3.8 +/- 0.6 and 4.4 microns(2)/1000 +/- 0.1 respectively, BB-IM
      was positively correlated to the % volume of fibrosis (r = 0.83, P < 0.0003).
      Both measurements were positively correlated to R-R interval (BBV-IM: r = 0.83, P
      < 0.0001; % volume of fibrosis: r = 0.87, P < 0.001) and negatively correlated to
      cardiac weights (BBV-IM: r = -0.79, P < 0.0005; % volume of fibrosis: r = -0.75,
      P < 0.001). CONCLUSION: Beat to beat changes in ventricular repolarization
      attributable to mechanoelectric transduction can be detected at the body surface
      by means of BBV-IM.

PMID- 9539859
TI  - Lipid peroxidation, arachidonic acid and products of the lipoxygenase pathway in
      ischaemic preconditioning of rat heart.
AB  - OBJECTIVE: Preconditioning with brief intermittent periods of ischaemia is known
      to provide protection against ischaemic injury. It has been suggested that
      myocardial ischaemia also activates phospholipase A2, which releases arachidonic
      acid from phospholipids. In the present study the possible role of phospholipid
      peroxidation, arachidonic acid and products of the lipoxygenase pathway in
      cellular mechanisms of ischaemic preconditioning was examined. METHODS: Isolated,
      buffer-perfused rat hearts were freeze-clamped at the end of preconditioning (a
      cycle of 5 min global ischaemia +5 min reperfusion) and at the end of 30 min
      global ischaemia and analysed for non-esterified fatty acids and fatty acids in
      the 2-position of phospholipid. In a separate set of experiments, hearts
      pretreated with a lipoxygenase inhibitor, nordihydroguaiaretic acid (NDGA), were
      subjected to 30 min regional ischaemia and 120 min reperfusion. Infarct size was
      determined by tetrazolium staining and the ischaemic risk zone with fluorescent
      particles. RESULTS: Myocardial levels of arachidonic as well as of linoleic and
      docosahexaenoic acid were significantly elevated by preconditioning. Also, the
      level of peroxidized polyunsaturated fatty acids (measured as hydroxy conjugated
      dienes) in myocardial phospholipid was significantly increased: 101.4 +/- 16.8
      nmol/g versus 51.2 +/- 7.3 nmol/g tissue dw in the control group, p < 0.05. Pre
      treatment of hearts with 5 microM NDGA blocked the infarct limiting effects of
      preconditioning: infarct size was 37.4 +/- 6.4% of risk zone in control, 9.0 +/-
      0.9% in the preconditioning group and 27.7 +/- 3.8% in the preconditioning + NDGA
      group (p < 0.05 vs. i.p., n.s. vs. control). CONCLUSION: Our findings provide
      evidence for the involvement of phospholipase A2 and lipoxygenase derived lipid
      second messengers in ischaemic preconditioning of the isolated rat heart.

PMID- 9539860
TI  - Hypothermia extends the cardioprotection by ischaemic preconditioning to coronary
      artery occlusions of longer duration.
AB  - OBJECTIVE: To test the hypothesis that mild hypothermia potentiates the
      cardioprotection afforded by ischaemic preconditioning so that infarct size
      limitation can be obtained after coronary artery occlusion (CAO) durations which
      exceed the cardioprotective range (> 90 min) of either hypothermia or ischaemic
      preconditioning alone. METHODS: Four groups of anaesthetized rats were subjected
      to different durations of CAO: (i) normothermia (N, 36.5-37.5 degrees C, n = 29),
      (ii) normothermia + ischaemic preconditioning (N + IP, 15 min CAO followed by 10
      min of reperfusion, n = 35), (iii) hypothermia (H, 30-31 degrees C, n = 31) and
      (iv) hypothermia + ischaemic preconditioning (H + IP, n = 24). Infarct size
      (IA/AR) was determined after 3 hours of reperfusion using trypan blue to
      delineate the area at risk (AR) from non-risk region and nitroblue tetrazolium to
      delineate infarcted area (IA) from viable myocardium. RESULTS: In N the CAO
      duration versus infarct size relation had a sigmoid shape with virtually no
      infarction occurring at 15 min CAO and 56 +/- 5% of the area at risk being
      infarcted at 30 min CAO reaching a plateau of 71 +/- 2% at 60 min CAO.
      Hypothermia produced a rightward shift of the relation resulting in an
      approximately 15 min delay in onset of infarction. Ischaemic preconditioning
      produced a similar reduction in infarct size (23 +/- 4%) at 30 min CAO compared
      to hypothermia (13 +/- 3%) but also limited infarct size at 45 min to 36 +/- 3%
      and at 60 min CAO to 50 +/- 3% suggesting a slowing of infarct progression.
      Neither intervention limited IA/AR produced by 120 min CAO. In H + IP, combined
      hypothermia and ischaemic preconditioning resulted in synergistic infarct size
      reduction so that at 45 min and 60 min CAO IA/AR was reduced to 17 +/- 3% and 23
      +/- 3%, respectively, and even at 120 min CAO to 58 +/- 5%, which was
      significantly smaller than during normothermic control conditions (p < 0.05 vs.
      N). CONCLUSION: Mild hypothermia limited IA/AR modestly but markedly enhanced the
      cardioprotection afforded by ischaemic preconditioning in the in situ rat heart
      so that irreversible damage produced by even prolonged coronary artery occlusions
      was limited.

PMID- 9539861
TI  - Protection afforded by preconditioning to the diabetic heart against ischaemic
      injury.
AB  - OBJECTIVE: The aim of this study was to assess whether the cardioprotective
      effect of ischaemic preconditioning (IPC) on endothelial function in coronary
      arteries and myocardial function is affected in the streptozotocin-induced
      diabetic rat heart. METHODS: Isolated hearts, perfused under constant flow
      conditions, were exposed to 30 min of partial ischaemia (flow rate 1 ml min-1)
      followed by 20 min of reperfusion. RESULTS: In the diabetic group (without
      ischaemia or IPC), infusion of 10 microM serotonin (5-HT), an endothelium
      dependent, and 3 microM sodium nitroprusside (SNP), an endothelium-independent
      vasodilator, in the coronary bed preconstricted with 0.1 microM U-46619 induced a
      marked vasodilation. Ischaemia, either without or with preconditioning with a
      single 5 min ischaemia and 10 min reperfusion (IPC1) before ischaemia, was
      accompanied by a reduced 5-HT-induced vasodilation in diabetic hearts. In
      contrast, IPC1 preserved the response to 5-HT in non-diabetic hearts. A more
      extensive IPC with 3 periods of 5 min ischaemia followed by 5 min reperfusion
      (IPC3) preserved the vasodilation produced by 5-HT in both diabetic and non
      diabetic hearts. IPC3 increased the recovery of d P/dtmax and d P/dtmin during
      the 30 min ischaemic period and during reperfusion in all hearts. In contrast,
      IPC1 had no effect on myocardial recovery in either groups. Adenosine pre
      treatment started 30 min before ischaemia mimicked IPC3, preserving the
      vasodilation to 5-HT and improving myocardium recovery in both groups. When
      adenosine was started 15 min before ischaemia, vasodilation to 5-HT was preserved
      in non-diabetic hearts only. CONCLUSIONS: These results suggest that IPC affords
      protection to endothelial function in resistance coronary arteries of diabetic
      hearts. To achieve this protection, a more extensive IPC is needed, which may be
      related to a longer exposure to adenosine.

PMID- 9539862
TI  - Development of heart failure following isoproterenol administration in the rat:
      role of the renin-angiotensin system.
AB  - OBJECTIVE: High dosages of catecholamines induce cardiomyocyte necrosis and
      interstitial fibrosis in rats. We investigated whether this initial damage is
      followed by the development of heart failure and assessed the particular role of
      the renin-angiotensin system using ramipril. METHODS AND RESULTS: Following the
      administration of 0 mg or 150 mg isoproterenol/kg 6 groups of Wistar rats were
      followed for 2 or 16 weeks: Sham, isoproterenol, isoproterenol + ramipril.
      Isoproterenol induced significant increases of echocardiographically measured
      left ventricular end-diastolic posterior wall thickness and dimension, whereas
      ramipril treatment significantly attenuated these changes. Left ventricular end
      diastolic pressure was markedly increased in isoproterenol-treated rats and
      normalized following ramipril. Isoproterenol rats were further characterized by
      hormonal activations including transient elevations of plasma renin activity,
      aldosterone and cardiac angiotensin converting enzyme activity.
      Histomorphological characterization of isoproterenol-treated hearts demonstrated
      cardiomyocyte necrosis and reparative fibrosis. Ramipril treatment only slightly
      reduced the amount of necrosis as well as the expression of extracellular matrix
      proteins. CONCLUSIONS: In rats, a toxic dosage of isoproterenol caused
      characteristic myocardial damage that subsequently resulted in mild heart
      failure. Ramipril administration following isoproterenol was highly effective to
      attenuate hemodynamic and hormonal alterations as well as the development of left
      ventricular hypertrophy, but had only little influence on the expression of
      extracellular matrix proteins. Since angiotensin converting enzyme inhibition had
      no impact on the initial myocardial injury, the development of heart failure in
      this model seems to require functional integrity of the renin-angiotensin system.

PMID- 9539863
TI  - Improvement of left ventricular function and cardiovascular neural control after
      endoventriculoplasty and myocardial revascularization.
AB  - OBJECTIVE: To investigate the effects of endoventriculoplasty (EVP) and
      myocardial revascularization on left ventricular function and on sympathovagal
      balance modulating sinus node and vasomotor activity, we studied patients with
      left anterior, septal or anteroseptal ventricular aneurysm, before and after
      surgery. It has been demonstrated that, compared to the standard aneurismectomy,
      EVP associated with coronary grafting has a lower operative mortality and
      improves ventricular function, clinical status and prognosis. METHODS: We
      collected pre- and post-operative echocardiographic and angiographic data to
      determine morphological and hemodynamic changes. The pre- and post-operative
      neural cardiovascular control was assessed by power spectrum analysis of heart
      rate and systolic arterial pressure (SAP) variabilities during rest and tilt.
      RESULTS: As expected, post-operative ventricular function improved significantly:
      ejection fraction increased from 33 +/- 2 to 46 +/- 3% (p < 0.01) when assessed
      by echocardiography and from 40 +/- 4 to 55 +/- 5% (p < 0.01) when assessed by
      angiography; left ventricular end-diastolic pressure fell from 22 +/- 3 to 13 +/-
      2 mmHg (p < 0.05). Pre-operatively sympathovagal balance responsiveness was
      blunted: tilt test did not induce, in respect to resting values, any significant
      change in low frequency (LFRR) and high frequency (HFRR) components of RR
      variability (in normalized units, n.u.) and in LFSAP. Post-operatively, tilt
      induced significant changes in LFRR and HFRR (in n.u.), in LF/HF ratio and LFSAP
      in respect to resting values. The pre- and post-operative percent differences-
      delta%--, from rest to tilt, of LFRR, HFRR, LF/HF and LFSAP were also
      significantly different (p < 0.01, p < 0.05, p < 0.05, p < 0.05). In addition, we
      compared data obtained from survivors and non-survivors (6 out of 19 patients
      died within 4 months because of heart failure). Non-survivors were characterized
      by significantly lower RR variance (184 +/- 80 vs. 1193 +/- 309 ms2 at rest, 196
      +/- 87 vs. 546 +/- 104 ms2 during tilt, p < 0.05) and lower LFRR (15 +/- 7 vs. 61
      +/- 6 at rest, 23 +/- 10 vs. 58 +/- 6 during tilt, in n.u., p < 0.01).
      CONCLUSIONS: (1) The improvement of ventricular function induced by EVP and
      myocardial revascularization is accompanied by a restored capability to oscillate
      of cardiovascular neural regulatory mechanisms; (2) the drastic reduction of
      variance and LF component from RR variability seems to be associated with an
      ominous outcome.

PMID- 9539864
TI  - Low-dose aspirin improves in vivo hemodynamics in conscious, chronically
      infarcted rats.
AB  - OBJECTIVE: The equivalent of the clinically used low (= antiplatelet)-dose
      aspirin, inhibited collagen deposition in the non-infarcted myocardium in rats
      with myocardial infarction. In the present study, the in vivo hemodynamic
      consequences of this daily low-dose aspirin were investigated in conscious,
      chronically instrumented, infarcted rats. METHODS: Rats, treated with 25 mg/kg
      aspirin daily from 2 days before to 3 weeks after coronary artery ligation, were
      chronically instrumented with an electromagnetic flow-probe and arterial and
      venous catheters, to record cardiac output, and arterial and venous blood
      pressure, respectively, in the conscious freely moving animal. In parallel,
      isolated hearts were studied with regard to left ventricular stiffness
      (pressure/volume relationships), maximal cardiac perfusion (adenosine), and in
      vitro heart rate and beta-adrenergic responsiveness. Plasma catecholamine levels
      were measured. RESULTS: Aspirin normalized the increased heart rate after
      infarction, at a preserved cardiac output. This was accompanied by a (non
      significant) increase in stroke volume, at unchanged cardiac loading conditions.
      The lower heart rate after aspirin was due to reduced intrinsic heart rate rather
      than to lower sympathetic activation of the heart, since similar effects were
      observed in isolated perfused hearts, while circulating levels of catecholamines
      and beta-adrenergic responsiveness were not influenced. The improved stroke
      volume was not explained by reduced left ventricular stiffness or increased
      maximal perfusion after aspirin. CONCLUSION: In addition to the antithrombotic
      action, effects of low-dose aspirin on cardiac remodeling could be associated
      with favorable hemodynamic effects, as reflected by a lower heart rate for the
      same cardiac output. Although the underlying mechanisms are still unknown, it
      suggests a clinically relevant beneficial effect which deserves further
      investigation.

PMID- 9539865
TI  - Clenbuterol induces cardiac hypertrophy with normal functional, morphological and
      molecular features.
AB  - OBJECTIVE: Several pharmacological agents have been shown to produce
      'physiological' or 'pathological' hypertrophy based on their functional
      characteristics. The aim of this study was to examine the features of cardiac
      hypertrophy induced by the selective beta 2-adrenergic agonist, clenbuterol.
      METHODS: Cardiac hypertrophy was induced in 7-week-old Sprague-Dawley rats by
      daily injections of clenbuterol for 3 weeks. Thyroxine and isoproterenol were
      also used to produce cardiac hypertrophy to serve as positive controls for
      physiological and pathological hypertrophy, respectively. Left ventricular
      function was determined using an isolated rat heart preparation. Ventricular
      samples were used for morphological examination while interstitial collagen was
      measured using high-pressure liquid chromatography. Expression of sarcoplasmic
      reticulum Ca(2+)-ATPase2a (SERCA2a) and phospholamban (PLB) were measured by dot
      blot analysis. RESULTS: Clenbuterol treatment induced 26% left ventricular
      hypertrophy. These hearts demonstrated normal systolic isovolumic parameters and
      diastolic (active relaxation and passive stiffness) function. In addition, left
      ventricular concentration of collagen and morphology was normal as were the
      expression of SERCA2a and PLB mRNA. CONCLUSION: These results suggest that
      clenbuterol-induced hypertrophy is 'physiological' in terms of its function,
      extracellular structure and gene expression.

PMID- 9539866
TI  - Differential myocardial abundance of collagen type I and type III mRNA in dilated
      cardiomyopathy: effects of myocardial inflammation.
AB  - OBJECTIVE: The collagen subtypes I (Col I) and III (Col III) are essential
      components of the cardiac extracellular matrix (ECM) maintaining the functional
      integrity of the heart. Histological, immunohistological, and biochemical
      studies, however, demonstrate characteristical changes of the ECM in dilated
      cardiomyopathy, myocarditis, ischemic cardiomyopathy, and hypertensive heart
      disease. METHODS: In order to investigate possible effects of inflammatory
      processes on mRNA abundance of Col I and Col III, we examined 24 patients with
      the presumptive clinical diagnosis of dilated cardiomyopathy (EF = 30 +/- 11%).
      12 Patients were classified as idiopathic dilated cardiomyopathy without any
      evidence of myocardial inflammation; the remaining 12 patients were classified as
      inflammatory cardiomyopathy due to the immunohistologically documented
      inflammatory myocardial process. RESULTS: Quantification of reverse transcription
      polymerase chain reaction (RT-PCR) products revealed significant differences as
      to the mRNA abundance ratio Col III/Col I between subgroups of patients with
      inflammatory cardiomyopathy (1.16 +/- 0.18) and idiopathic dilated cardiomyopathy
      (2.77 +/- 0.65) regardless of left ventricular dysfunction (p < or = 0.05).
      CONCLUSION: It is not yet known, whether different Col III/Col I ratios
      differentially influence diastolic compliance. Our data suggest that inflammatory
      mechanisms seen in inflammatory cardiomyopathy influence the mRNA abundance of
      collagen subtypes I and III.

PMID- 9539867
TI  - Combined potassium and calcium channel antagonistic activities as a basis for
      neutral frequency dependent increase in action potential duration: comparison
      between BRL-32872 and azimilide.
AB  - OBJECTIVE: The effects of BRL-32872, azimilide and a selective blocker of the
      delayed rectifier potassium current, E-4031, were measured at two different basic
      cycle lengths (BCL), 300 and 1000 ms. Calcium channel antagonists of sarcolemmal
      (verapamil and nitrendipine) and sarcoplasmic reticulum (ryanodine) membranes
      were used to investigate whether the inhibition of the calcium current or the
      calcium release from the sarcoplasmic reticulum could alter the reverse-rate
      dependence of E-4031 on action potential duration (APD). METHODS: Guinea pig
      isolated papillary muscles were superfused with a Tyrode solution maintained at
      37 degrees C and stimulated at a BCL of 300 or 1000 ms. The standard
      microelectrode technique was used to record action potential parameters and to
      study the effects of azimilide, BRL-32872 and E-4031. E-4031 was superfused at
      increasing concentrations (0.01, 0.03, 0.1 and 0.3 microM) in the absence or in
      the presence of verapamil (0.3 microM), nitrendipine (0.03 microM) or ryanodine
      (0.1 microM). RESULTS: BRL-32872 and azimilide induced a self-limited
      concentration-dependent increase in APD. The effect of BRL-32872 was not
      dependent on the stimulation frequency whereas the effect of azimilide was
      significantly reduced at the shorter BCL. E-4031 induced a concentration
      dependent increase in APD at both stimulation BCL. The increase in APD was
      significantly more pronounced in fibres stimulated at a BCL of 1000 ms than in
      fibres stimulated at a BCL of 300 ms, characterising the reverse-frequency
      dependent effect of class III antiarrhythmic agents. The reverse-frequency
      dependence in action potential prolongation induced by E-4031 was significantly
      reduced in the presence of a low concentration of verapamil (0.3 microM),
      nitrendipine (0.03 microM), or ryanodine (0.1 microM. CONCLUSION: The results
      show that BRL-32872, in contrast to azimilide, does not induce the reverse-rate
      dependency of action potential prolongation typically produced by class III
      antiarrhythmic agents such as E-4031. Our results also show that reverse-rate
      dependency induced by E-4031 can be reduced by the simultaneous administration of
      a low concentration of a calcium channel antagonist or an inhibitor of the
      release of calcium from the sarcoplasmic reticulum. It is thus suggested that
      compounds with a suitable balance of potassium and calcium antagonistic
      activities may have less adverse effects than purely selective potassium channel
      blockers.

PMID- 9539868
TI  - Mitochondrial gene expression is impaired by ethanol exposure in cultured chick
      cardiac myocytes.
AB  - OBJECTIVE: A depression in cytochrome c oxidase (COX) activity occurs following
      chronic embryonic ethanol exposure in vivo. The aim of this study was to examine
      the effect of chronic ethanol exposure on COX activity in isolated cardiac cells
      maintained in vitro. Additionally, the mechanism by which ethanol produces an
      impairment in COX activity was evaluated by examining mitochondrial gene
      expression. METHODS: Spontaneously beating cardiac myocyte cultures were
      established from 10-day embryonic chick hearts. Various concentrations of ethanol
      (0-250 mM) were introduced at the time of plating and cells were harvested over 7
      days. COX activity was determined in myocyte homogenates. The levels of nuclear
      encoded (COXIV) and mitochondrial-encoded (COXII) subunit proteins were measured
      by Western blotting. Relative levels of mitochondrial DNA and the mitochondrially
      encoded COXIII mRNA were determined by Southern and Northern blotting. RESULTS: A
      consistent decrease in COX activity in ethanol-exposed cardiac myocytes of
      approximately 30% was observed with an ethanol concentration of 25 mM. Increasing
      the ethanol concentration to 250 mM produced only a minor enhancement of this
      effect, while severely decreasing cellular viability. The content of the
      mitochondrially-encoded COXII subunit was reduced by ethanol exposure, while that
      of the nuclear-encoded COXIV subunit was unchanged. The content of the
      mitochondrially-encoded COXIII mRNA was unchanged by ethanol exposure. However,
      prolonged ethanol exposure produced an increase in mitochondrial DNA levels in
      cardiac myocytes. CONCLUSIONS: Ethanol exposure of cardiac myocytes produces
      deficits in COX activity in the absence of systemic variables, indicating that
      ethanol has a direct effect on cardiac mitochondria. The ethanol-induced decrease
      in COX activity is correlated with a specific decrease in at least one
      mitochondrially-encoded gene product, COXII. No changes were observed in the
      level of the nuclear-encoded COXIV subunit, indicating that expression of this
      nuclear-encoded gene is not impaired by ethanol exposure.

PMID- 9539869
TI  - Thyroid status and postnatal changes in subsarcolemmal distribution and isoform
      expression of rat cardiac dihydropyridine receptors.
AB  - OBJECTIVE: The aim was to analyze the early postnatal changes in myocardial
      density, subsarcolemmal localization and isoform expression of dihydropyridine
      receptors in rat ventricle and the influence of thyroid status on these changes.
      METHODS: Newborn rats were treated from postnatal day 2 with L-triiodothyronine
      (T3) or 6-n-propyl-2-thiouracil )PTU) and ventricles were collected on day 1, 7
      and 14. Radioligand binding and cell fractionation (density gradient
      centrifugation) techniques were used to determine the tissue density of various
      receptors and their subcellular localization. To analyze dihydropyridine receptor
      alpha 1 subunit isoform expression, cDNA fragments corresponding to a large
      portion of motif IV were amplified by reverse transcriptase-polymerase chain
      reaction and treated with appropriate restriction endonucleases to determine the
      frequency of splicing events at the level of motif IV. RESULTS: The myocardial
      density of dihydropyridine receptors increased 3-fold from day 1 to day 14 in
      control rats, and this increase occurred predominantly in membrane entities
      equilibrating at high densities in sucrose gradient, that is, presumably, in
      junctional structures (dyadic couplings). This maturation was delayed after PTU
      treatment, and somewhat accelerated by excess T3. The proportion of mRNA variants
      typical of foetal heart (IVS3A variant and 'deleted' variant, showing a 33
      nucleotide deletion at the level of the extracellular loop between IVS3 and IVS4)
      decreased with age in control rats. This reduction was delayed after treatment
      with PTU but was not influenced by excess T3. CONCLUSION: Hypothyroidism impaired
      the early postnatal maturation of dihydropyridine receptors as regards both their
      concentration into junctional structures and the decrease in the relative
      expression of alpha 1-subunit mRNA variants typical of foetal heart.

PMID- 9539870
TI  - Metabolic alterations in the chronically denervated dog heart.
AB  - OBJECTIVE: Previous studies have shown that chronic cardiac denervation impairs
      myocardial glucose oxidation. To investigate this further we tested whether the
      tissue content of glucose transporters, activity of glycolytic enzymes or
      metabolic capacity of pyruvate dehydrogenase were altered. Moreover, we
      investigated whether the decline in glucose utilization was associated with an
      upregulation of proteins and enzymes involved in fatty acid handling. Chronic
      cardiac denervation results also in decreased left ventricular efficiency. We
      explored whether alterations in mitochondrial properties could be held
      responsible for this phenomenon. METHODS: Twelve adult dogs were included in the
      study. In 6 of them chronic cardiac denervation was accomplished by surgical
      ablation of the extrinsic nerve fibers. The other 6 dogs were sham-operated.
      Biopsies were obtained from the left ventricle after 4-5 weeks of denervation.
      The content or enzymatic activity of proteins involved in fatty acid and glucose
      handling was assessed. Features of glutamate oxidation were measured in freshly
      isolated mitochondria. RESULTS: The content or activity of a set of fatty acid
      handling proteins did not change during chronic cardiac denervation. In contrast
      GLUT1 content significantly increased in the chronically denervated left
      ventricle, while the active form of pyruvate dehydrogenase declined (p < 0.05).
      Glutamate oxidation characteristics in freshly isolated mitochondria were not
      affected by chronic denervation. CONCLUSION: The impairment of glucose oxidation
      in the chronically denervated myocardium is most likely caused by a decline of
      pyruvate dehydrogenase in its active form. It is unlikely that the decrease in
      work efficiency is caused by alterations in mitochondrial properties.

PMID- 9539872
TI  - Selective impairment of HCO3(-)-dependent pHi regulation by
      lysophosphatidylcholine in guinea pig ventricular myocardium.
AB  - OBJECTIVE: The aim was to examine the effects of lysophosphatidylcholine (LPC),
      an amphiphilic lipid metabolite in ischemic myocardium, on intracellular pH
      (pH(i)) regulatory systems in guinea pig papillary muscles. METHODS: In CO2/HCO(3
      )-buffered Tyrode solution, pH(i), intracellular Na+ activity (aNai) and membrane
      potential of isolated guinea pig papillary muscles were measured using ion
      selective microelectrode and conventional microelectrode. Standard ammonium
      prepulsing with 20 mM NH4Cl was used to produce an intracellular acid load, and
      effects of LPC on the pH(i) recovery from acidosis were evaluated in the absence
      and presence of a transport inhibitor. RESULTS: LPC acidified the resting pH(i)
      by 0.03 +/- 0.01 pH units (n = 15, p < 0.01) concomitantly with a slight decrease
      in resting membrane potential and an increase in aNai in quiescent preparations.
      The pH(i) recovery rate from an intracellular acid load was decreased to 83 +/-
      4% of the control value by 30 microM LPC (n = 8, P < 0.05) but not by 30 microM
      phosphatidylcholine (PC). In the presence of 10 microM 5-(N,N-hexamethylene)
      amiloride (HMA), a Na(+)-H+ exchange inhibitor, LPC still slowed pH(i) recovery
      from an intracellular acid load to 77 +/- 4% of the control (n = 5, P < 0.05).
      However, LPC failed to alter the pH(i) recovery rate in the presence of 4,4'
      diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS, 0.5 mM), a Na(+)-HCO3-
      symport inhibitor. CONCLUSION: LPC impairs Na(+)-HCO3- symport but not Na(+)-H+
      exchange, and LPC may potentiate its arrhythmogenic action by intensifying the
      intracellular acidosis in ischemic myocardium.

PMID- 9539871
TI  - Dual cardiac microdialysis to assess drug-induced changes in interstitial purine
      metabolites: adenosine deaminase inhibition versus adenosine kinase inhibition.
AB  - OBJECTIVE: The purpose of this study was: 1) to evaluate a dual microdialysis
      technique coupled with local drug administration in the regionally ischemic
      rabbit heart, and; 2) to assess the ischemia-induced changes in interstitial
      fluid (ISF) adenosine during inhibition of adenosine deaminase or adenosine
      kinase. METHODS: Two microdialysis probes were implanted parallel to each other
      and separated by 5 mm in myocardium perfused by a branch of the left coronary
      artery. Probes were used to sample myocardial ISF and to deliver drugs locally to
      the myocardium; purine metabolite concentrations in the collected dialysate were
      used as indices of ISF levels. Three groups of pentobarbital-anesthetized rabbits
      were studied. In a control group (n = 6), both probes were perfused with Krebs
      Henseleit buffer. In the second and third groups, one probe was perfused with
      buffer, whereas the other probe was perfused with buffer containing 1 mM erythro
      2-(2-hydroxy-3-nonyl)adenine (EHNA) (n = 5), an adenosine deaminase inhibitor, or
      10 microM iodotubercidin (n = 9), an adenosine kinase inhibitor. All animals were
      exposed to 30 min of regional myocardial ischemia followed by 60 min of
      reperfusion. RESULTS: In the control group, similar increases in dialysate purine
      metabolites during ischemia were observed in both probes. Locally administered
      EHNA increased dialysate adenosine prior to ischemia and decreased dialysate
      inosine and hypoxanthine. During ischemia, the increase in dialysate adenosine in
      the EHNA-perfused probe was markedly augmented, while the increases in inosine
      and hypoxanthine were attenuated. In contrast, local infusion of iodotubercidin
      did not alter dialysate purine metabolites before ischemia, but there was a
      modest augmentation of adenosine during ischemia. These data illustrate the
      feasibility of dual microdialysis for assessing the effect of locally
      administered compounds on interstitial metabolite concentration in the regionally
      ischemic rabbit heart. Furthermore, adenosine deaminase inhibition has a more
      profound adenosine augmenting effect than adenosine kinase inhibition in the
      rabbit heart.

PMID- 9539873
TI  - Altered cardiac hormone and contractile protein messenger RNA levels following
      left ventricular myocardial infarction in the rat: an in situ hybridization
      histochemical study.
AB  - OBJECTIVES: Cardiac remodeling secondary to myocardial infarction is associated
      with hypertrophy of surviving myocardium and altered cardiac gene expression. The
      present study examined the spatiotemporal expression of cardiac contractile
      protein and peptide hormone mRNA following left ventricular myocardial infarction
      (LVMI) in the rat heart. METHODS: LVMI was produced in Wistar rats by ligation of
      the left anterior descending coronary artery and mRNA levels of cardiac alpha
      action (sACT), ventricular myosin light chain-2(MLC-2v), beta-myosin heavy chain
      (beta-MHC) and pre-proatrial natriuretic peptide (ppANP) were examined at 24 h, 1
      and 4 weeks) post-LVMI by in situ hybridization histochemistry with 35S-labeled
      oligonucleotide probes. RESULTS: Infarct size, determined at 1 week post-LVMI,
      was 44.5 +/- 2.7% of the combined left ventricular epi- and endocardial surface
      area. Myocyte fiber width, reflecting cellular hypertrophy, was increased in left
      ventricular, mid-septal and mid-right ventricular muscle fibers by 11-20% at 1
      week post-LVMI (P < 0.05) and by 24-29% at 4 weeks (P < 0.05). At 24 h, 1 and 4
      weeks post-LVMI, heart- and lung/body weight ratios were significantly elevated
      compared to sham-operated rats (1.3-1.8-fold, P < 0.01 and 1.6-2.9-fold, P <
      0.005, respectively). PpANP mRNA levels in the left ventricle were increased 3.8-
      and 3.3-fold at 1 and 4 weeks (P < 0.05), with highest levels in the epicardium,
      papillary muscle, infundibulum and apex of the chamber. Septal and right
      ventricular ppANP mRNA levels were highest at 24 h post-LVMI (2.1- and 2.6-fold
      increase, P < 0.05) and remained elevated at 4 weeks, with maximum levels at the
      left endocardial surface of the septum and apex of the chambers. Atrial levels of
      cACT mRNA were increased 1.9-fold at 1 week post-LVMI (P < 0.05) and remained
      elevated at 4 weeks. Skeletal ACT mRNA, not normally expressed in the adult rat
      heart, was induced as early as 24 h post-LVMI in both atria, the septum and right
      ventricle, with discrete hybridization signal detected at the apex of the
      chambers and in the right ventricular free-wall, and later (1 week) in the left
      ventricular epicardium. MLC-2v mRNA levels were unaltered post-LVMI, except for a
      transitory loss of expression at 24 h in the left atria, ventricle and apical
      septum. In contrast, ventricular beta-MHC mRNA was markedly induced in regions
      containing increased ppANP mRNA, with a maximal 3.0- and 4.0-fold induction (P <
      0.05) seen at 1 and 4 weeks in the left ventricle and a 3.7-fold induction at 4
      weeks in the septum and right ventricle (P < 0.05). CONCLUSION: The regional
      increases in induced cardiac hormone and contractile protein mRNA in similar
      subchamber regions of the rat heart post-LVMI implies mutual activation by
      mechanical and/or neuroendocrine stimuli in the transcriptional response to
      myocardial overload.

PMID- 9539874
TI  - Effects of norepinephrine on expression of IGF-1/IGF-1R and SERCA2 in rat heart.
AB  - OBJECTIVES: The effects of norepinephrine on expression of cardiac genes during
      pathological cardiac growth and heart failure are not fully understood. Tissue
      insulin-like growth factor 1 (IGF-1) and its receptor (IGF-1R) play an important
      role in the regulation of the hyperplastic capacity of cardiac myocytes.
      Sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2), on the other hand, is important in
      regulating cardiac contractile function. The present study examined the effects
      of elevated levels of NE on expression of IGF-1/IGF-1R and SERCA2 mRNAs. METHODS:
      Rats were infused with NE using osmotic minipumps for 3 and 6 days at a rate of
      50 micrograms/kg/h and also at a higher dose (130 micrograms/kg/h) for 6 and 14
      days. Levels of expression of IGF-1/IGF-1R and SERCA2 mRNAs were determined by
      ribonuclease protection assay and by Northern blotting, respectively. RESULTS: NE
      treatment significantly increased IGF-1 mRNA levels in both left- and right
      ventricle; however, levels of IGF-1R increased in the left- but not the right
      ventricle. By contrast, NE infusion at both the lower dose and the higher dose
      failed to alter expression of SERCA2 mRNA. CONCLUSION: Our results suggest that
      NE treatment differentially regulates expression of IGF-1 and IGF-1R in the
      ventricles of rat heart and that NE appears not to affect expression of SERCA2
      mRNA.

PMID- 9539875
TI  - Calculation of plasma concentrations of intra-arterially infused compounds in
      forearm plethysmography.
AB  - OBJECTIVE: Forearm blood flow plethysmography is a widely accepted in vivo
      technique for pharmacologic and functional studies in peripheral resistance
      vessels and veins. Pharmacological effects on forearm blood flow (FBF) are
      usually expressed by means of dose-response relationships. This approach does not
      consider the influence of variations in FBF on the actual plasma concentrations
      of compounds infused, and is less suitable for quantitative comparison of the
      pharmacologic characteristics of different compounds. The aim of this study was
      to validate an equation to estimate the plasma concentrations of intra-arterially
      infused compounds. This was done at different levels of FBF, using an indicator
      dilution technique with constant rate infusions of indocyanine green (ICG) and
      inulin. METHODS: ICG (0.5 mg/min) and insulin (5 mg/min) were infused into the
      brachial artery in the presence of sodium nitroprusside (10 ng/kg/min; to obtain
      high FBF), vehicle (0.9% saline; for intermediate FBF), and methoxamine (1
      microgram/kg/min; for low FBF), FBF was measured using venous occlusion
      plethysmography in six healthy male volunteers. Plasma concentrations of the
      indicators, measured in venous blood samples, were compared with the calculated
      values. RESULTS: Excellent correspondence was observed between calculated and
      measured plasma concentrations for both ICG and inulin. Venous plasma
      concentrations of ICG (> or = 95% protein binding) reached steady-state within
      four min independent of FBF. Alternatively, the time required for venous plasma
      concentrations of inulin (not bound to protein) to reach steady-state appeared
      dependent on FBF. CONCLUSION: Total plasma concentrations of intra-arterially
      infused drugs can be appropriately estimated at the level of the arterioles by
      the proposed equation.

PMID- 9539876
TI  - Human monocyte-endothelial cell interaction induces platelet-derived growth
      factor expression.
AB  - OBJECTIVE: The purpose of this study was to investigate whether the synthesis of
      platelet-derived growth factor (PDGF), a major mitogen and chemoattractant for
      vascular smooth muscle cells, was induced by the direct cell-to-cell interaction
      between human monocytes and umbilical vein endothelial cells (ECs). METHODS: PDGF
      protein and mRNA expression were determined by cellular ELISA,
      immunohistochemical and Northern blot analyses. RESULTS: Coculture of monocytes
      and ECs secreted a large amount of PDGF into the supernatant, whereas culture of
      ECs or monocytes alone induced low levels of PDGF production. In Northern blot
      analysis, substantial amounts of PDGF-A and -B mRNA were induced by coculture of
      monocytes with ECs. Immunohistochemistry revealed that PDGF-B chain protein was
      detectable in both ECs and monocytes. PDGF production by ECs induced by
      conditioned medium of the coculture was significantly inhibited by Abs against
      interleukin-1 beta (IL-1 beta) and tumor necrosis factor- alpha (TNF alpha).
      CONCLUSIONS: These results indicate that the direct cell-to-cell interaction
      between human monocytes and ECs induces PDGF synthesis in both types of cells,
      suggesting that PDGF produced locally by monocyte-EC adhesive interaction plays
      an important role in the pathogenesis of atherosclerosis by promoting the
      migration and accumulation of vascular smooth muscle cells.

PMID- 9539877
TI  - Blood flow resistance during hemodilution: effect of plasma composition.
AB  - OBJECTIVES: To investigate the causes of wide variations in reported effects of
      hemodilution on flow resistance of vascular beds. METHODS: (a) In a meta-analysis
      of 28 prior studies, resistance values at hematocrits of zero (R0) and 0.45
      (R0.45) were derived. Study design characteristics (presence of vasodilatory
      reserve or leukocytes, species, tissue, hemodiluent) were tested by ANOVA for
      their relation to the ratio R0/R0.45. (b) Experiments were performed to determine
      flow resistance during hemodilution in the rat mesentery with (n = 8) and without
      (n = 11) pretreatment with heparinase, which modifies the endothelial glycocalyx.
      (c) A mathematical flow simulation for mesenteric microvascular networks was used
      to predict resistance effects of hemodilution and of a hypothetical layer on the
      endothelial surface. RESULTS: (a) In prior studies using native plasma for
      hemodilution R0 averaged 50 +/- 8% of R0.45, while in studies using artificial
      solutions R0 averaged 32 +/- 12% of R0.45. The larger reduction of flow
      resistance upon dilution with artificial media is independent of viscosity and
      oncotic pressure. Other design characteristics did not show strong significant
      effects. (b) Present experiments showed large reductions of flow resistance with
      saline hemodilution which were nearly halved after heparinase pretreatment. (c)
      Resistance effects of hemodilution with plasma or after heparinase treatment
      agree with model predictions based on tube flow rheology of blood. The larger
      resistance effects of dilution with artificial media can be explained by the
      removal of an endothelial surface layer of approximately 1.5 microns thickness.
      CONCLUSIONS: The results imply that changes of plasma composition, due to use of
      artificial infusion media, influence peripheral resistance and tissue perfusion.
      They are consistent with the hypothesis that interactions between endothelial
      glycocalyx structures and plasma components lead to formation of a thick layer at
      the endothelial surface which increases flow resistance.

PMID- 9539878
TI  - A new heart failure model in rat by an end-to-side femoral vessel anastomosis.
AB  - OBJECTIVE: The aim of this study was to develop a new shunting procedure for
      producing heart failure in the rat incorporating microvascular techniques and
      avoiding an abdominal operation. METHOD: We performed an end-to-side anastomosis
      between the femoral vein and the femoral artery just proximal to their
      trifurcation into the saphenous, epigastric, and distal femoral vessels. RESULTS:
      Of the 15 rats which underwent this procedure, six died within 48 h. The nine
      surviving animals were sacrificed and examined six weeks following surgery. All
      nine had developed cardiac hypertrophy and cardiac failure. CONCLUSION: This
      model provides a relatively simple and reproducible means of creating high output
      heart failure and cardiac hypertrophy in the rat without necessitating abdominal
      surgery.

PMID- 9539880
TI  - Structure and reactivity of small arteries in aging.
AB  - OBJECTIVE: Increased pulse pressure has been observed in aging subjects, but the
      impact on the structure and reactivity of small arteries has been scarcely
      evaluated. METHODS: This study presents the modifications of vascular structure
      and function observed in female rats of 5, 18 and 32 months of age, and their
      relation to the prevailing hemodynamic status. Geometry and reactivity of
      perfused and pressurized basilar and mesenteric small arteries were analyzed in
      vitro using a video dimension analyzer. RESULTS: Mean arterial pressure was
      similar in the three age groups, and only pulse pressure was increased in the
      oldest group. Media thickness and cross sectional area increased in basilar and
      mesenteric arteries of the oldest rats and these structural abnormalities were
      positively related to pulse pressure but not to mean, systolic or diastolic
      arterial pressure. Only minor changes of vascular reactivity were noted with age:
      there was a decreased contraction to angiotensin II in mesenteric arteries and an
      enhanced contraction to endothelin-1 in the basilar arteries. CONCLUSION: In
      conclusion, aging is associated with increased pulse pressure and hypertrophy of
      basilar and mesenteric resistance arteries, suggesting that this hemodynamic
      variable may influence cerebral and peripheral vascular structure in aging.

PMID- 9539879
TI  - Exposure to oxidized low-density lipoprotein in vivo enhances intimal thickening
      and selectively impairs endothelium-dependent dilation in the rabbit.
AB  - OBJECTIVES: Based on in vitro studies, oxidized low-density lipoprotein (oxLDL)
      has been implicated in atherogenesis and the associated deficiency in endothelium
      dependent relaxation. The aim of this study was to investigate the effects of in
      vivo exposure to oxLDL on intimal thickening and relaxing behaviour. METHODS:
      Intimal thickening was evoked by the placement of silicone collars around the
      carotid arteries of the rabbit for 3 or 14 days. OxLDL (Cu(2+)-oxidized, 7
      micron/h) or the vehicle phosphate-buffered saline (PBS) was infused in the
      collars via subdermally implanted osmotic minipumps. RESULTS: The collared
      vessels receiving PBS developed discrete intimal thickening after 14 days
      (intima/media (I/M) ratio 11 +/- 2%). OxLDL infusion resulted in intimal
      thickening after 3 days and significantly enhanced the intimal thickness by 14
      days (I/M ratio 98 +/- 16%). Collaring alone for 3 or 14 days and 3 days exposure
      to oxLDL did not impair the endothelium-dependent relaxations to acetylcholine or
      calcium ionophore, nor to the NO donors glyceryl trinitrate (GTN) and S-nitroso-N
      acetylpenicillamine (SNAP). However, the sensitivity to acetylcholine was
      decreased after exposure to oxLDL for 14 days (-logEC50 oxLDL 6.95 +/- 0.11 vs.
      7.52 +/- 0.11 collar alone) and the maximal relaxation to the endothelium
      dependent agonist was reduced by 50%, this in the presence of a virtually intact
      endothelium. Complete relaxation was still obtained with the nitric oxide donors.
      CONCLUSION: Our results show for the first time that local vascular exposure to
      oxLDL in vivo promotes intimal thickening and inhibits endothelium-dependent
      dilation, thereby supporting an active role for oxLDL in the morphological and
      functional changes observed in atherosclerotic blood vessels.

PMID- 9539881
TI  - Regional variation in appearance of vascular contractile endothelin-B receptors
      following organ culture.
AB  - OBJECTIVE: The aim of this study was to investigate the appearance of contractile
      endothelin (ET)-B receptors following organ culture in different vascular
      regions. METHOD: The contractile responses of vascular smooth muscle induced by
      ET-1 and the selective ETB receptor agonist sarafotoxin 6c (S6c) were
      investigated in circular segments representing eight vascular regions in the rat
      (aorta, femoral artery, mesenteric artery, branch of the mesenteric artery,
      proximal and distal parts of the caudal artery, femoral and mesenteric veins). To
      allow the ETB receptor to be expressed, the segments were placed in organ culture
      for 1 to 5 days. Pharmacological characterisation of the ET receptors was
      performed in mesenteric arterial segments. All contractile responses were
      measured in percentage of K(+)-induced contraction. RESULTS: ET-1 induced strong
      concentration-dependent contractions of all fresh (not cultured) segments. S6c
      had negligible effects on all fresh vessels with the exception of the mesenteric
      vein, where a small contraction was seen. After 1 day of organ culture all tested
      segments, with the exception of aorta and the proximal part of the caudal artery,
      showed concentration-dependent contractile responses to S6c which were further
      augmented after 5 days of culture. The ET-1-induced responses were only slightly
      affected by organ culture. Contractions induced by S6c were more enhanced in
      small arteries and veins than in larger arteries. Furthermore, the S6c-induced
      response was more pronounced in the mesenteric region as compared to the
      hindlimb. In fresh mesenteric arterial segments FR139317 (ETA receptor
      antagonist) and bosentan (ETA/ETB receptor antagonist) but not IRL 2500 (ETB
      receptor antagonist) shifted the ET-1-induced concentration-response curve in
      parallel to the right. In contrast, after organ culture the S6c-induced
      concentration-response curves were shifted parallel to the right in the following
      potency order: IRL 2500 > bosentan > FR139317. CONCLUSION: During normal
      conditions, the ETA receptor is the dominating mediator of endothelin-induced
      contraction in eight different vascular regions. Furthermore, this study
      indicates that most of the vessels have the ability to develop contractile ETB
      receptors and that this plasticity differs in vascular regions.

PMID- 9539882
TI  - In permeabilised endothelial cells IP3-induced Ca2+ release is dependent on the
      cytoplasmic concentration of monovalent cations.
AB  - OBJECTIVE: IP3-induced Ca2+ release from the intracellular stores plays a role in
      the production of vasoactive substances in the endothelium. In many cells, Ca2+
      release is accompanied by an inward movement of K+ whose function may be to
      dissipate the potential difference created by the loss of positive charge from
      the internal stores. The existence of such a mechanism in endothelial cells was
      investigated. METHODS: Using saponin-permeabilised bovine aortic endothelial
      (BAE) cells, the effects of K+ on the IP3-induced 45Ca2+ release were
      investigated. RESULTS: Replacement of K+ with NMG inhibited IP3 (3 microM)
      induced 45Ca2+ release by 55%. The ability of other ions to allow IP3-induced
      45Ca2+ release was found to be K+ = Na+ > Cs+ > Rb+ >> Co2+. The K+ channel
      blockers TEA, 4AP and 3,4-DAP were found to significantly inhibit IP3-induced
      45Ca2+ release by 16%, 36% and 27%, respectively. CONCLUSIONS: The data suggest
      that Ca2+ release from intracellular stores is partly dependent on a movement of
      K+ through K+ channels in the store membranes. In contrast, 9AA (400 microM) and
      substitution with Co2+ abolished the response. Therefore, K+ is important for IP3
      induced 45Ca2+ release, but other ions are also likely to act as counter-ions.
      9AA and Co2+ probably act on sites other than those involving ER monovalent
      cation channels. The possibility that a counter-ion system plays a role in the
      activation of endothelial cells is discussed.

PMID- 9539883
TI  - Incommunicable knowledge? Interpreting and applying the results of clinical
      trials and meta-analyses.

PMID- 9539884
TI  - The problem of cogent subgroups: a clinicostatistical tragedy.

PMID- 9539885
TI  - Within trial variation--a false trail?

PMID- 9539886
TI  - Clinical versus statistical considerations in the design and analysis of clinical
      research.

PMID- 9539887
TI  - Use of a short-form screening procedure to detect unrecognized functional
      disability in the hospitalized elderly.
AB  - We performed an observational cohort study to test the ability of a short-form
      screening procedure to detect unrecognized functional disability, as well as its
      capacity to predict clinical outcome. This screening procedure was administered
      to 198 consecutive patients within 48 hours of admission. Clinical outcomes upon
      discharge from the acute care hospital and at 3 months were analyzed according to
      the number of functional disabilities present on admission. This brief test
      identified a mean of 1.8 and a median of 1 previously unrecognized functional
      disabilities per patient. The presence of two or more functional disabilities on
      admission (48% of the study population) was significantly associated with a
      negative outcome upon discharge (relative risk = 1.73; CI, 1.33-2.25; p = 0.0001)
      and at 3 months after discharge (relative risk = 1.34; CI, 1.10-1.64; p = 0.003)
      confirming the reliability of the short-form screening procedure.

PMID- 9539888
TI  - Multidimensionality in instrumental and basic activities of daily living.
AB  - Although the use of self-reported ADL (activity of daily living) scales has a
      long history, the Katz-based assumptions of unidimensionality and hierarchy are
      increasingly found lacking, and ADLs alone are found to underestimate dysfunction
      and disability. Data from nearly 8900 elderly respondents in the community sample
      of the 1991 Canadian Study of Health and Aging were used to examine the
      measurement properties of a modified version of the Older Americans Research
      Survey (OARS) ADL and IADL items combined. A multidimensional factor structure
      was revealed, with three levels of functional ability possessing internal
      consistency. We conclude that assumptions regarding ADL/IADL unidimensionality
      and hierarchy are not always valid, and that ADL and IADL items should be
      considered in combination to capture a greater range of functional disability
      prevalence. We also suggest that expectations of precise measurement of
      functional dependence by (I)ADL scales should perhaps be relaxed to the goal of
      simply differentiating broad levels of self-reported functioning (such as basic,
      intermediate, and complex), within which some tasks are roughly equivalent.
      Because these scales are widely used as screening tools and in shaping policy, we
      suggest that employing a more empirically grounded measurement standard has the
      potential to reduce bias due to item complexity and task specificity, facilitate
      standardization, and more reliably predict outcomes.

PMID- 9539889
TI  - Tiredness in daily activities at age 70 as a predictor of mortality during the
      next 10 years.
AB  - This study examined whether self-reported tiredness in mobility and activities of
      daily living is predictive of mortality, when controlled for global self-rated
      health, smoking, and socio-demographic factors. The investigation is part of the
      1984 longitudinal study of the residents of Glostrup, Denmark, born in 1914, and
      included 734 men and women who were interviewed about mobility, activities of
      daily living, self-rated health, smoking, and socio-demographic factors, when
      they were 70 years old. Ten years later, in November 1994, information about
      deaths was obtained from the Central National Register. When controlled for the
      other variables tiredness in mobility was an independent predictor of mortality
      during the next 10 years among both women and men. The finding persisted when the
      analysis was performed on a restricted sample of non-disabled 70-year-old people.
      The results in the present study indicate that we have identified a subgroup of
      independent elderly people who are at risk of dying earlier than others.

PMID- 9539890
TI  - Balneotherapy and quality assessment: interobserver reliability of the Maastricht
      criteria list and the need for blinded quality assessment.
AB  - This study investigates aspects of the reliability of the Maastricht criteria
      list for quality assessment in systematic reviews, and whether blinded reviewing
      is necessary to prevent review bias. We used the data set of 12 articles from a
      systematic review concerning the efficacy of balneotherapy in patients with
      arthritis. Twenty reviewers participated of which two reviewers, who have been
      involved in developing the Maastricht criteria list, acted as reference standard.
      Half of all assessments were performed blindly. A high level of agreement was
      found between the reviewers and a high level of correlation with the reference
      standard. The quality scores between the blinded and unblinded assessment did not
      differ much. Based on the results we conclude that the Maastricht criteria list
      is a reliable instrument in quality assessment of clinical trials. Within the
      limits of this study we found no evidence that blinding is necessary to prevent
      review bias.

PMID- 9539891
TI  - Predicting future years of healthy life for older adults.
AB  - Cost-effectiveness studies often need to compare the cost of a program to the
      lifetime benefits of the program, but estimates of lifetime benefits are not
      routinely available, especially for older adults. We used data from two large
      longitudinal studies of older adults (ages 65-100) to estimate transition
      probabilities from one health state to another, and used those probabilities to
      estimate the mean additional years of healthy life that an older adult of
      specified age, sex, and health status would experience. We found, for example,
      that 65-year-old women in excellent health can expect 16.8 years of healthy life
      in the future, compared to only 8.5 years for women in poor health. We also
      provide estimates of discounted years of healthy life and future life expectancy.
      These estimates may be used to extend the effective length of the study period in
      cost-effectiveness studies, to examine the impact of chronic diseases or risk
      factors on years of healthy life, or to investigate the relationship of years of
      life to years of healthy life. Several applications are described.

PMID- 9539892
TI  - P-values and confidence intervals: two sides of the same unsatisfactory coin.
AB  - For both P-values and confidence intervals, an alpha level is chosen to set
      limits of acceptable probability for the role of chance in the observed
      distinctions. The level of alpha is used either for direct comparison with a
      single P-value, or for determining the extent of a confidence interval.
      "Statistical significance" is proclaimed if the calculations yield a P-value that
      is below alpha, or a 1-alpha confidence interval whose range excludes the null
      result of "no difference." Both the P-value and confidence-interval methods are
      essentially reciprocal, since they use the same principles of probabilistic
      calculation; and both can yield distorted or misleading results if the data do
      not adequately conform to the underlying mathematical requirements. The major
      scientific disadvantage of both methods is that their "significance" is merely an
      inference derived from principles of mathematical probability, not an evaluation
      of substantive importance for the "big" or "small" magnitude of the observed
      distinction. The latter evaluation has not received adequate attention during the
      emphasis on probabilistic decisions; and careful principles have not been
      developed either for the substantive reasoning or for setting appropriate
      boundaries for "big" or "small." After a century of "significance" inferred
      exclusively from probabilities, a basic scientific challenge is to develop
      methods for deciding what is substantively impressive or trivial.

PMID- 9539893
TI  - Aminorex, dexfenfluramine, and primary pulmonary hypertension.
AB  - BACKGROUND: In the late 1960s, an epidemic of primary pulmonary hypertension
      (PPH) occurred in Europe shortly after the introduction of aminorex fumarate, a
      potent anorexigen. A recently published case-control study from Europe reported
      that use of other anorexigens (the most prevalent of which was dexfenfluramine)
      was also associated with an increased risk of PPH. This led to warnings of a
      repeat epidemic, especially after the introduction of dexfenfluramine on the
      North American market. OBJECTIVE: To compare the epidemiologic associations of
      PPH with aminorex and dexfenfluramine, both with respect to strength of
      association (estimate of relative risk) and public health impact (etiologic
      fraction) and thus to assess the potential for a new epidemic of PPH. METHODS: We
      constructed a "synthetic" case-control study for aminorex based on reported case
      series from Berne and Basel, Switzerland, and a random population sample from
      Hanover, Germany, and compared the results with those recently reported for
      dexfenfluramine. Control rates of exposure were used to estimate population
      exposure prevalences and, hence, etiologic fractions. RESULTS: The estimated odds
      ratio (and 95% confidence interval) for the association between PPH and any
      exposure to aminorex was 97.8 (78.9-121.3), with a corresponding etiologic
      fraction of 77%. The corresponding figures for dexfenfluramine were 3.7 (1.9-7.2)
      and 17%, respectively. CONCLUSION: The strong association between aminorex and
      PPH probably led to a 5-fold increase in PPH incidence, and thus a very
      noticeable epidemic. The association with dexfenfluramine would result in an
      increase in incidence of only 20%. Based on the available evidence, a repeat PPH
      epidemic seems unlikely.

PMID- 9539894
TI  - On the use of "incidence" and "prevalence".

PMID- 9539895
TI  - Smoking--time to ring the alarm bells again.

PMID- 9539896
TI  - Health policy--the process and the politics.

PMID- 9539897
TI  - The weighty issues of perimenopausal and menopausal hormone therapy.

PMID- 9539898
TI  - Smoking behaviours of Australian adults in 1995: trends and concerns.
AB  - OBJECTIVES: To estimate the prevalence of smoking among Australian men and women
      in 1995 and to examine trends in smoking prevalence in Australia over the past 10
      years. DESIGN: A representative sample of adults participated in face-to-face
      interviews conducted by a large market research company. PARTICIPANTS: 2819 men
      and 2880 women over the age of 16. MAIN OUTCOME MEASURE: Self-reported smoking
      behaviours assessed by standard questions. RESULTS: Overall, 27.1% of men and
      23.2% of women were smokers of tobacco (factory-made cigarettes, pipes, cigars or
      roll-your-own cigarettes). This difference in smoking prevalence of men and women
      was significant. More men (32.1%) than women (21.7%) were past smokers and more
      women (53.4%) than men (39.3%) had never been regular smokers. On average, male
      smokers smoked about 20 factory-made cigarettes a day, while women smoked about
      18. Occupation and education levels were inversely related to smoking prevalence.
      Comparisons with earlier data suggest that the decline in smoking prevalence seen
      in previous surveys has ceased. However, the number of cigarettes consumed daily
      decreased between 1992 and 1995. In the period between 1983 and 1989, when per
      capita expenditure on adult antismoking campaigns rose, smoking prevalence
      declined, but levelled off thereafter in a period when expenditure on campaigns
      fell. CONCLUSION: Failure to find a continuing decline in prevalence of smoking
      among the Australian population is of great concern and indicates the importance
      of continuing and extending antismoking programs.

PMID- 9539900
TI  - Two contiguous outbreaks of dengue type 2 in north Queensland.
AB  - OBJECTIVES: To investigate two outbreaks of dengue type 2 in north Queensland,
      one in the Torres Strait beginning in late 1996, the other in a Cairns suburb in
      early 1997. DESIGN: Epidemiological investigation of all laboratory-confirmed
      cases of dengue, entomological investigation of the local environment, and
      laboratory analysis of the isolated dengue viruses. MAIN OUTCOME MEASURES:
      Numbers of confirmed and of locally acquired cases; virus serotype; comparison of
      nucleotide sequences between viruses isolated from the two outbreaks; and Breteau
      Index (BI = number of containers with larvae of the mosquito vector Aedes aegypti
      found per 100 houses investigated) on the affected islands and in the Cairns
      suburb. RESULTS: There were 201 confirmed cases of dengue in the Torres Strait
      outbreak, which lasted nearly seven months, and seven confirmed cases in the
      Cairns outbreak, which lasted about nearly 11 weeks. Most (190) were confirmed as
      dengue type 2. Nucleotide sequencing of viruses isolated from the two outbreaks
      showed they were identical. Ae. aegypti breeding sites were very common on the
      five Torres Strait islands surveyed (BIs, 73-219--high risk), but less so in the
      Cairns suburb (BI, 23). The most common breeding sites were water storage
      reservoirs, particularly rainwater tanks, on the outer Torres Strait islands,
      discarded containers (such as plastic containers, buckets and tyres) on Thursday
      Island, and garden items (such as flowerpot bases and jars) in Cairns.
      CONCLUSIONS: The virus responsible for the Cairns outbreak was most probably
      introduced from the Torres Strait, whereas the virus responsible for the Torres
      Strait outbreak was imported from Papua New Guinea. Preventive strategies
      tailored to specific locations are needed to reduce breeding of Ae. aegypti in
      north Queensland, and the consequent risk of future outbreaks of dengue.

PMID- 9539899
TI  - Hormone therapy in women in the menopause transition. Randomised, double-blind,
      placebo-controlled trial of effects on body weight, blood pressure, lipoprotein
      levels, antithrombin III activity, and the endometrium.
AB  - OBJECTIVE: To determine whether hormone treatment of women during the menopause
      transition induces changes in body weight, blood pressure, lipoprotein levels,
      antithrombin III activity, and the endometrium. DESIGN: Prospective, randomised,
      placebo-controlled, double-blind, 12-month study, with crossover at 6 months.
      SETTING: Outpatient clinic of a city hospital. PARTICIPANTS: 105 apparently
      healthy women in the menopause transition (40-52 years), with menstrual function,
      who were experiencing minor menopausal symptoms, were selected from the general
      population by advertising. INTERVENTIONS: Active arm--oral conjugated oestrogens
      (0.625 mg daily) and cyclic medroxyprogesterone acetate (10 mg daily) on Day 14
      27 of each menstrual cycle; placebo arm--placebos of both medications. MAIN
      OUTCOME MEASURES: Excess change from baseline associated with active compared
      with placebo treatment for all variables; effect of order of treatment. RESULTS:
      Baseline biochemical values were similar for both treatment-order groups, but
      baseline blood pressures and body weights were higher in the group receiving
      placebo first. With treatment, there were no differences in overall values for
      body weight and blood pressure (P > 0.4), and order of treatment had no
      significant influence (P > 0.3). There were no differences in total and low
      density lipoprotein cholesterol levels, overall or with order of treatment.
      Active treatment increased high density lipoprotein (HDL) cholesterol levels
      (overall and when placebo was given first; P = 0.001), and triglyceride levels
      (when active treatment was given first; P = 0.03). There was no overall treatment
      effect, but a significant order-of-treatment effect, on antithrombin III activity
      (mean levels were decreased by active treatment to a greater extent when it was
      given first; P = 0.02). The endometrium showed only physiological changes
      regardless of treatment. CONCLUSIONS: The lack of significant excess change in
      anthropometry, lipoprotein levels, antithrombin III activity, and endometrial
      histology in women given hormone treatment compared with placebo is reassuring.
      The increase in HDL cholesterol level is an extra benefit. Our study provides
      conclusive evidence that hormone treatment does not produce weight gain in women
      during the menopause transition.

PMID- 9539901
TI  - Polymyositis caused by a new genus of nematode.
AB  - We report two patients who presented with increasing malaise and myalgia, and had
      biopsy-proven polymyositis. Their conditions deteriorated after corticosteroid
      treatment, and repeat muscle biopsies showed adult and larval nematodes.
      Anthelminthic treatment was completely successful in both cases. The infecting
      nematode appears to belong to a new genus and is, to our knowledge, the first
      known muspiceoid nematode to infect humans. Its life cycle and the route of
      infection are unknown.

PMID- 9539902
TI  - Why Australia needs minimum standards of deliberation for public health.

PMID- 9539903
TI  - New drugs, old drugs. Beta-adrenoceptor blocking agents.

PMID- 9539904
TI  - Jobless. Unemployment and young people's health.
AB  - Morrell, Taylor and Kerr, from the University of Sydney's Department of Public
      Health, review the evidence of an association between unemployment and
      psychological and physical ill-health in young people aged 15-24 years. Aggregate
      data show youth unemployment and youth suicide to be strongly associated. Youth
      unemployment is also associated with psychological symptoms, such as depression
      and loss of confidence. Effects on physical health have been less extensively
      studies; however, there is some evidence for an association with raised blood
      pressure. Finally, the prevalence of lifestyle risk factors (cannabis use and,
      less consistently, tobacco and alcohol consumption) is higher in unemployed
      compared with employed young people.

PMID- 9539905
TI  - Common child and adolescent psychiatric problems and their management in the
      community.

PMID- 9539906
TI  - Increase Pap smear uptake.

PMID- 9539907
TI  - Conventional Pap smears are unreliable.

PMID- 9539908
TI  - Women have a right to the most accurate result.

PMID- 9539909
TI  - PAPNET superior to rapid rescreening.

PMID- 9539910
TI  - Depression in young people.

PMID- 9539912
TI  - Australian trends in hospitalisation and mortality associated with chronic heart
      failure.

PMID- 9539911
TI  - Aspects of diagnosis and staging of non-small-cell lung cancer.

PMID- 9539913
TI  - "Tomorrow's doctors" and beyond: medical education in the UK.

PMID- 9539915
TI  - Clinical usage of intravenous immunoglobulins in Auckland.
AB  - AIMS: To review the indications for prescription of intravenous immunoglobulin
      (IVIg), in Auckland and the associated adverse effects. METHODS: All patients who
      received IVIg infusions in four major hospitals in Auckland in 1996 were
      identified from blood bank records. Clinical details were recorded from case
      notes. RESULTS: One hundred and thirty-five cases were identified and 131 records
      were available for review. Hypogammaglobulinaemia (n = 38) and thrombocytopenia
      (n = 38) were the two most common indications for 44% of Primary
      hypogammaglobulinaemia accounted for IVIg. the IVIg prescribed. IVIg was only
      used in one patient with hypogammaglobulinaemia secondary to chronic lymphocytic
      leukaemia and in one case of graft-versus-host disease. Adverse reactions were
      noted in 13 cases (10%). Headache (n = 4) and fever (n = 4) were the most
      commonly recorded side-effects. One patient developed acute renal failure after
      IVIg infusion. Written consent was documented in 7 patients (5%). CONCLUSIONS:
      The indications for IVIg prescription were generally consistent with the
      recommendations of the Australasian Society of Blood Transfusion. Use of IVIg in
      haematological conditions other than immune thrombocytopaenic purpura was
      infrequent. Most of the IVIg infusions were administered uneventfully but some
      minor side effects were recorded and one significant clinical event may have been
      causally related to IVIg infusion.

PMID- 9539914
TI  - Psychiatric illness in a New Zealand sample of young people making serious
      suicide attempts.
AB  - AIM: To examine the extent of psychiatric illness amongst young people making
      medically serious suicide attempts and control subjects. METHOD: Using a case
      control design, 129 young people making serious suicide attempts were contrasted
      with 153 randomly selected community controls on a series of measures of current
      and lifetime DSM-III-R diagnoses of mental disorders. RESULTS: Individuals making
      suicide attempts were characterised by high rates of current mental disorder
      (89.5%), current comorbidity (54.3%), lifetime histories of psychiatric disorder
      (90.7%) and previous suicide attempts (52.7%). At the time of the suicide
      attempt, those making serious attempts had elevated rates of the following
      disorders: affective disorders (70.5%), substance use disorders (38.8%), anxiety
      disorders (14.7%), eating disorders (8.5%) and antisocial disorders (34.9%).
      CONCLUSIONS: Young people who made medically serious suicide attempts had high
      rates of a range of mental disorders, and of comorbid disorders, at the time of
      the suicide attempt. They had high rates of lifetime histories of mental
      disorders and previous suicide attempts. The implications of these findings for
      the development of strategies to manage, treat and prevent suicidal behaviours in
      young people are discussed.

PMID- 9539916
TI  - Injecting behaviours and prevalence of hepatitis B, C and D markers in New
      Zealand injecting drug user populations.
AB  - AIM: To determine the seroprevalence of hepatitis C virus (HCV), hepatitis B
      virus (HBV) & hepatitis D virus (HDV) markers of infection among injecting drug
      user populations in New Zealand and to examine the relationship between
      demographic features, risk behaviours and infection. METHODS: A total of 323
      current injecting drug users completed a questionnaire that explored their needle
      and syringe using behaviours. Information was collected on injection pattern,
      sharing behaviours and methods of cleaning needles and syringes. Two hundred and
      forty-one respondents gave blood samples which were tested for hepatitis B, C and
      D markers. RESULTS: Over half the respondents (59%) were male and 41% were
      female. Most (89%) identified as European. Sixty-four percent were anti-HCV
      positive. The likelihood of infection increased with age and duration of
      injecting. Forty-one percent (33/81) of those aged 25 or under, sixty-four
      percent (45/70) of those aged 26-30 and eighty-seven percent (78/90) over 30 were
      anti-HCV positive. Those who tested anti-HCV positive had been injecting for an
      average of 12.0 years compared to 6.0 years for those were anti-HCV negative. The
      results for hepatitis B are to be reported fully at a later date. Sharing
      behaviour was also a factor although this was less important as an independent
      factor. Comparisons with earlier surveys suggested that there has not been a
      significant decline in the rate of sharing needles and syringes since the initial
      period following introduction of the needle exchange programme. CONCLUSION: The
      prevalence of hepatitis C infection is common among injecting drug users of all
      ages. Without a significant reduction in sharing behaviour, particularly among
      younger injecting drug users, it is unlikely that the prevalence of hepatitis C
      among injecting drug users will decline in the future. Evidence suggests that the
      carriage of hepatitis C is higher than that of hepatitis B which would help
      explain the differing rates of prevalence. However, the risk of future
      transmission of other parenterally transmitted diseases remains high without a
      further significant decline in sharing behaviour.

PMID- 9539917
TI  - General practitioner attitudes toward mandatory reporting of doctor-patient
      sexual abuse.
AB  - AIM: To explore general practitioner attitudes toward mandatory reporting of
      doctor-patient sexual abuse. METHODS: Anonymous questionnaire mailed to a
      randomised sample of 217 New Zealand general practitioners. Attitudes toward
      mandatory reporting of doctor-patient sexual contact, seductive or sexually
      demeaning behaviour were appraised including an indication of whom the perceived
      appropriate reporting body should be. RESULTS: Forty-seven per cent of
      respondents supported the notion of mandatory reporting for doctor-patient sexual
      contact, 42% for sexually demeaning behaviour and 35% for seductive verbal
      behaviour. These respondents indicated that the most appropriate body to report
      to was a Doctor's Health Advisory Service. CONCLUSION: There was a lack of strong
      consensus on mandatory reporting of doctor-patient sexual abuse.

PMID- 9539919
TI  - Post circumcision meatal stenosis: 12 years' experience.
AB  - AIMS: To study the presentation of meatal stenosis as a complication of
      circumcision done in boys of neonatal or nappy age. METHODS: A total of 50
      patients were studied. These patients had meatotomy performed to treat meatal
      stenosis. All the patients had circumcision during the neonatal period or in the
      nappy age. Meatal stenosis was defined as change in the appearance of the
      delicate lips of the urinary meatus, with loss of elliptical shape to a circular
      shape because of fibrosis or scarring, with visually apparent narrowing. Patients
      with this appearance and no symptoms, but who had presented with a hernia,
      undescended testes or some other unassociated condition and had meatotomy were
      for the purpose of this study classed as the incidental group. Patients who were
      symptomatic and had the meatal stenosis as defined above were classed as the
      symptomatic group. RESULTS: Sixteen patients (total n = 50) had the diagnosis of
      meatal stenosis made incidentally. Thirty four patients, (68% of the total
      treated by meatotomy) presented to the clinic, being symptomatic due to meatal
      stenosis. The median age at presentation of the symptomatic group was 48 months
      (range 3 months-13 years) following circumcision. In all the symptomatic patients
      meatotomy alleviated the symptoms. All the operated patients were seen between
      one to three months following the operation and discharged. There were no late
      presentations with recurrence of meatal stenosis or complications of the
      treatment. CONCLUSION: Meatal stenosis is an under recognised complication of
      circumcision done in neonatal and nappy aged boys. Symptomatic presentation from
      meatal stenosis can be very late.

PMID- 9539918
TI  - Griseofulvin and terbinafine in the treatment of tinea capitis in children.
AB  - AIM: To compare the effectiveness of griseofulvin and terbinafine in the
      treatment of tinea capitis in children. METHOD: Twenty four consecutive patients
      with culture proven tinea capitis were treated randomly with griseofulvin (10
      mg/kg/day for 8 weeks) or terbinafine (62.5-250 mg/day for 4 weeks). Outcome was
      determined by absence of clinical signs, hair regrowth or negative mycology.
      RESULTS: Twenty four patients (16 male, 8 female) were treated. Age ranged
      between 2 and 15 years (mean 4.8). Seven patients presented with kerion, the
      remainder with a scaling and patchy alopecia pattern of tinea capitis. The
      responsible organisms were Microsporum canis (17 cases) and Trichophyton
      verrucosum (7 cases). Fourteen children were treated with griseofulvin and 10
      with terbinafine. By three months follow up, 19 patients had cleared completely
      with good new hair regrowth. Three children had no active disease but only
      minimal new hair growth. One child (griseofulvin group) had no hair regrowth but
      was culture negative. She had sustained significant dermal and subcutaneous skin
      damage requiring plastic surgery. The other (terbinafine group) had ongoing
      active kerion. CONCLUSION: Both griseofulvin and terbinafine are equally
      effective in the treatment of tinea capitis.

PMID- 9539920
TI  - Sale of cigarettes to school children.

PMID- 9539921
TI  - Alternative remedies.

PMID- 9539922
TI  - Methicillin-resistant S. aureus in the suburbs.

PMID- 9539923
TI  - Physical treatment of shoulder complaints.

PMID- 9539924
TI  - Can accident or occupation cause fibromyalgia.

PMID- 9539925
TI  - The Zuma report card--an upper-second pass.

PMID- 9539927
TI  - Genetics and TB--the secret in the genes?

PMID- 9539929
TI  - Medical editors trial amnesty (META).

PMID- 9539928
TI  - Social health insurance options.

PMID- 9539930
TI  - Opportunities and threats in proposed changes to birth and death registration.

PMID- 9539931
TI  - Health care achievement and challenges in the Western Cape.

PMID- 9539932
TI  - Reconstructing and developing the health system--the first 1,000 days.
AB  - This paper attempts to document the successes and failures of the Department of
      Health during the first 1,000 days of the Government of National Unity. The
      achievements of the Department are reflected against the backdrop of the legacies
      inherited by the current Ministry and Department.

PMID- 9539933
TI  - Immunogenicity of a low-cost hepatitis B vaccine in the South African Expanded
      Programme on Immunisation.
AB  - BACKGROUND: A low-cost, 'flash' heat-inactivated hepatitis B vaccine with
      enhanced immunogenicity allowing for a relatively low dose (Hepaccine B; Cheil
      Foods and Chemicals, Korea) was introduced into the South African Expanded
      Programme on Immunisation during 1995 to immunise infants against hepatitis B. To
      determine the seroresponse of this vaccine in South Africa, a country with a high
      hepatitis B virus (HBV) prevalence, a field trial was conducted in a rural health
      clinic. METHODS: The immunogenicity of Hepaccine B, containing 1.5 micrograms/0.5
      ml, was studied in 186 black infants attending the Soshanguve III clinic, north
      west of Pretoria. Infants receiving three consecutive doses in the anterolateral
      thigh at 6, 10 and 14 weeks were monitored. The doses were administered
      concurrently with their routine oral polio vaccine (OPV) and diphtheria,
      pertussis and tetanus (DPT) immunisations. Vaccine side-effects were recorded.
      Blood specimens were collected 3 months after the final vaccination. Sera were
      tested for antibodies to hepatitis B surface antigen (anti-HBs) by IMx AUSAB
      (Abbott Laboratories, USA). Levels of anti-HBs were determined by comparison with
      standard reference preparations and expressed in mlU/ml. RESULTS: Side-effects of
      the vaccine were minor, with limited local reaction at the site of
      administration. The anti-HBs seroconversion rate was 93.0%, based on a titre of >
      or = 10 mlU/ml with a geometric mean titre of 257.58 mlU/ml. CONCLUSIONS:
      Administration of 1.5 micrograms dose of Hepaccine B at 6, 10 and 14 weeks is
      safe and highly immunogenic in black South African infants, and this vaccine is
      suitable for use in countries with high HBV prevalences such as in Africa. The
      use of an economical hepatitis B vaccine would greatly facilitate the prevention
      of hepatitis B in these countries.

PMID- 9539934
TI  - Molecular diagnosis of multiple endocrine neoplasia type 2A.
AB  - OBJECTIVE: To identify by means of genetic analyses individuals who are at risk
      of developing medullary thyroid cancer that is a component of multiple endocrine
      neoplasia. SUBJECTS: A three-generation kindred with clinically and biochemically
      diagnosed medullary thyroid cancer. METHOD: Identification of a heterozygote
      mutation by nucleic acid sequencing and restriction analyses. RESULTS: A
      heterozygote T-->C (Cys-->Arg) mutation at codon 618 in exon 10 of the RET proto
      oncogene was identified in 4 family members who had previously been diagnosed
      with medullary thyroid cancer. The same mutation was also found in one of the
      proband's presymptomatic children who subsequently underwent a pre-emptive
      thyroidectomy. The genetic diagnosis was confirmed by histology. No mutations
      were detected in any other family members. CONCLUSION: Identification of
      heterozygote germline mutations in multiple endocrine neoplasia is direct, highly
      accurate and cost-effective. This study demonstrates that, appropriately used,
      molecular diagnosis can supersede conventional biochemical methods in the
      management of patients with inherited cancers.

PMID- 9539935
TI  - On-site screening for syphilis at an antenatal clinic.
AB  - OBJECTIVE: To determine the validity, predictive value and accuracy of the rapid
      plasma reagin card test performed on site to diagnose active syphilis in pregnant
      women so that immediate treatment can be offered to prevent congenital syphilis.
      DESIGN: Open, descriptive study. SETTING: Antenatal clinic, Mamelodi Hospital,
      Pretoria. PATIENTS: Four hundred and seventy-four pregnant women attending the
      antenatal clinic for the first time were entered into the study. METHODS: A rapid
      plasma reagin test was performed on site with no specialised equipment and the
      results were compared with those of the reference laboratory. RESULTS: In the
      event of rapid plasma reagin titres of 1:8 and higher, indicative of active
      syphilis, the on-site rapid plasma reagin test had a sensitivity of 90.5%. The
      test had a sensitivity of 100% if the rapid plasma reagin titres were 1:16 and
      higher. CONCLUSION: The on-site rapid plasma reagin test identified all women
      with rapid plasma reagin titres higher than 1:8. This implies that all women
      whose fetuses were in danger of acquiring congenital syphilis were identified at
      the clinic and could be treated immediately.

PMID- 9539936
TI  - A high rate of injury during the 1995 Rugby World Cup.
AB  - OBJECTIVE: To determine the frequency and nature of injuries sustained by the 416
      players from 16 countries participating in the 1995 Rugby World Cup played in
      South Africa in May/June 1995. METHODS: The study was a prospective analysis of
      all injuries requiring medical attention during that competition. Data were
      collected by the match doctors on duty at each of the venues at which the matches
      were played. Data were collated and analysed. RESULTS: There were 48 preliminary
      and 7 final-round matches. Of a total of 70 injuries during the tournament, 58
      occurred during the preliminary matches (frequency 30 injuries per 1000 player
      hours); the frequency was somewhat higher during the 7 final-round matches (43
      injuries per 1000 player hours). Overall injury frequency was 1 injury every 0.8
      matches during the preliminary and 1 every 0.6 matches during the final-round
      matches. Thirty per cent of injuries were to ligaments, 27% were lacerations and
      14% were muscle strains. The lower limb accounted for 42% of all injuries, the
      upper limb for 29% and the face for 17%. Fifty-six per cent of injuries occurred
      during the tackle phase of play, 23% during the ruck and maul, 11% during open
      play and 9% during foul play. The scrum and line-out together contributed only 1%
      of all injuries. Loose forwards suffered 25% of all injuries; centres and wings
      20%; prop forwards and half-backs 16% each; locks 14%; hookers 7% and fullbacks
      3%. One player suffered a paralysing spinal cord injury during a preliminary
      match. The incidence of catastrophic neck injuries in the tournament was
      therefore 4.6 per 10,000 player hours. CONCLUSIONS: The frequency of injury in
      this competition is the highest yet recorded in any group of rugby players. The
      risk of rugby injury is therefore greatest in the best players in the game,
      challenging the view that superior fitness, skill and experience can reduce the
      risk of rugby injury. In contrast, the larger size, greater speed and superior
      competitiveness and commitment of the best rugby players in the world would
      explain why they are at the highest risk of injury. The high frequency of injury
      in international rugby has implications for: (i) the frequency with which such
      matches should be played; and (ii) the number of players needed to complete a
      season of international rugby.

PMID- 9539937
TI  - Teleradiology in KwaZulu-Natal. A pilot project.
AB  - OBJECTIVE: This was a pilot teleradiology project connecting two secondary
      KwaZulu-Natal hospitals' radiography departments to a central Durban teaching
      hospital. The purpose of the study was to assess the usefulness of same-day
      teleradiology reports to the medical staff and whether such a service changed
      patient management. DESIGN: After 1 month's service at each hospital, the first
      200 teleradiology reports, original radiographs and patients' case notes were
      reviewed to determine whether any errors in interpretation of the radiographs had
      been made and whether the reports had changed patient management. RESULTS: The
      service changed patient management in 10% of cases. Undetected pathology was
      recognised by the radiologist in 20 patients--pulmonary tuberculosis in 10,
      spinal tuberculosis in 3, miliary tuberculosis in 2 and fractures in 5. Problems
      were encountered with transmission of data using the current telephone network,
      loss of data at the receiving station and the increased workload of the
      radiographer transmitting the data. CONCLUSIONS: Teleradiology services do make a
      positive impact on patient management in rural hospitals. However, there are many
      technical pitfalls that must be avoided in order to establish an effective
      service.

PMID- 9539938
TI  - The epidemic of Athens, 430-426 BC.
AB  - The Athenian epidemic of 430-426 BC, at the outbreak of the Peloponnesian War,
      caused the death of the great statesman, Pericles, decimated the population and
      contributed significantly to the decline and fall of classical Greece. In his
      remarkable documentation of the epidemic, Thucydides (who survived the disease)
      not only left us a clear clinical picture of the pestilence but also identified
      its infectious nature and the fact that it conferred at least partial immunity on
      survivors. As confirmed by a large number of scholars who studied the subject,
      Thucydides' description does not accurately fit any existing disease, but we
      suggest that analysis of the signs and symptoms, considered in conjunction with
      significant epidemiological evidence, narrows down the many possibilities to
      epidemic typhus, plague, arboviral disease (e.g. Rift Valley fever) and smallpox.
      Typhus and smallpox fit best, but we favour the latter for reasons given. Unless
      further primary sources of information become available (and this seems most
      unlikely), productive speculation as to the cause of Thucydides' epidemic has
      probably reached the end of the road.

PMID- 9539940
TI  - Intern training--is the system crippled forever?

PMID- 9539941
TI  - The neglected link in the tuberculosis control chain.

PMID- 9539942
TI  - Latex agglutination v. enzyme-linked immunosorbent assays for detection of
      antibodies to HIV in plasma from Lusaka, Zambia.

PMID- 9539943
TI  - 'Kickbacks'.

PMID- 9539944
TI  - A peri-anal abscess could be a tuberculous infection.

PMID- 9539945
TI  - The prevalence of mixed-species and antifolate-resistant malaria infections in
      Mpumalanga.

PMID- 9539948
TI  - Social phobia when using a second language.

PMID- 9539947
TI  - Jacob, Esau and longevity.

PMID- 9539949
TI  - Growth monitoring--do not throw the baby out with the bathwater.

PMID- 9539950
TI  - First report of microsporidiosis in South Africa.

PMID- 9539951
TI  - Hormone action and chromatin remodelling.
AB  - Current attention in transcriptional regulation is focused on the properties of
      coactivators and corepressors that mediate communication between sequence
      specific transcription factors, the basal transcriptional machinery and the
      chromatin environment. Nuclear and steroid hormone receptors represent the best
      understood transcription factors that utilize coactivators and corepressors. This
      review considers the access of these receptors to chromatin, the modifications of
      chromatin structure that the receptors instigate and the implications for
      transcriptional control. Nucleosome positioning and targeted histone modification
      emerge as central controlling elements for gene expression.

PMID- 9539952
TI  - Naturally occurring 2'-O-methylpurine nucleosides with hypotensive properties.
AB  - 2'-O-Methylinosine (1) has been isolated for the first time and shown to be an
      intrinsic hypotensive principle. Its probable in vivo precursor, 2'-O
      methyladenosine (3), showed stronger and even orally potent hypotensive activity.
      Resistance of the methyladenosine (3) against adenosine deaminase is thought to
      contribute to its long-lasting activity. The effect of both nucleosides (1 and 3)
      was not accompanied with any significant change in heart rate, which is often
      observed with adenosine.

PMID- 9539953
TI  - EGF-induced programmed cell death of human mammary carcinoma MDA-MB-468 cells is
      preceded by activation AP-1.
AB  - MDA-MB-468 is a human mammary adenocarcinoma cell line that overexpresses the
      epidermal growth factor (EGF) receptor and undergoes programmed cell death
      (apoptosis) in response to EGF treatment. Programmed cell death was shown to be
      greatly enhanced when cells were growth-arrested prior to EGF treatment.
      Apoptosis was characterized by an initial rounding up and detachment of the cells
      from their substrate starting about 12 h after EGF treatment, followed by
      chromatin condensation, nuclear fragmentation and oligonucleosomal fragmentation
      of the DNA at about 24 to 48 h. Cell death was dependent on de novo protein
      synthesis. We found a rapid induction of c-fos, c-jun and junB at the mRNA level
      after about 30 min of EGF treatment and a more delayed upregulation of fosB and
      fra-1. The junD gene was expressed in the absence of EGF, and it was moderately
      induced within 30 min of growth factor addition. The increase of the different
      fos and jun mRNAs were paralleled by an increase of activator protein-1 (AP-1)
      DNA binding activity. A characterization of the AP-1 complex revealed similar
      levels of several Fos and Jun proteins. Based on the kinetics of AP-1
      accumulation and cell death, it seems likely that AP-1 contributes to the
      apoptotic cell death of EGF receptor-overexpressing MDA-MB-486 cells.

PMID- 9539954
TI  - In situ localization of ACTH receptor-like mRNA in molluscan and human
      immunocytes.
AB  - Adrenocorticotropin hormone (ACTH) receptor-like messenger RNA was localized in
      molluscan hemocytes and human peripheral blood mononuclear cells by in situ
      hybridization using a digoxigenin-labelled bovine complementary DNA probe. These
      findings suggest that the ACTH receptor gene has been highly conserved during
      evolution. Moreover, these data represent further support for a relationship
      between the immune and neuroendocrine systems in invertebrates, as documented in
      our previous studies.

PMID- 9539956
TI  - Relationship between steady-state activation and availability of cardiac sodium
      channel: evidence of uncoupling.
AB  - The coupling between steady-state activation and availability from inactivation
      was characterized for the cardiac Na+ channel. To evaluate this coupling, we
      plotted the relationship between the conductance and availability curve midpoint
      potentials measured in 92 rat ventricular cardiomyocytes and applied a
      correlation analysis. We found a high correlation between the midpoints
      (correlation coefficient = 0.86, slope = 0.95) within the availability midpoint
      potential range positive to -100 mV. In contrast, the midpoints were not
      correlated in the myocytes (37 of 92 cells) having midpoint potential negative to
      -100 mV, indicating an uncoupling between activation and availability.

PMID- 9539955
TI  - Specific recombinogenic activity of a new polyene antibiotic.
AB  - A new antibiotic from Streptomyces sp., tetrapol A159, active against various
      fungi, a promising compound for the control of plant diseases, was studied for
      its genotoxic effects. It was produced at the Institute of Microbiological
      Preparations for Agriculture, Sofia, Bulgaria. The chemical was tested in three
      different test systems: a bacterial system, the Ames test for point mutations,
      the micronucleus test in bone marrow cells of rats for chromosomal aberrations
      and the fungal system of Aspergillus nidulans for mitotic recombination and
      aneuploidy. No increase in histidine revertants was observed in any of the TA100,
      TA98, TA1535 and TA1537 strains of Salmonella at concentrations ranging from 1 to
      4000 mg/plate. The results were also negative in the micronucleus test of bone
      marrow cells at concentrations from 124 to 600 mg/kg b.w., whereas a
      statistically significant threefold increase of mitotic crossovers was found in
      Aspergillus, at concentrations from 0.5 to 2.5 mg/ml.

PMID- 9539957
TI  - Cytogenic studies of Hynobiidae (Urodela). XIV. Analysis of the chromosome of a
      Chinese salamander, Batrachuperus pinchonii (David).
AB  - The chromosome number of a Chinese salamander, Batrachuperus pinchonii, was re
      examined Adults and embryonic specimens had a diploid number of 66, with 33
      bivalents during meiosis, in contrast to previous reported results. Furthermore,
      when C-banding analysis was performed with embryos, chromosomes with banding
      patterns homoeologous to those of Salamandrella keyserlingii and Hynobius species
      were found. It appears, therefore, that Batrachuperus, Salamandrella and Hynobius
      might be derived from a common ancestral species in eastern Asia.

PMID- 9539958
TI  - Production of insulin-like growth factor I (IGF-I) and IGF-binding proteins by
      rat intestinal stromal cells in vitro.
AB  - To determine if intestinal stromal cells secrete diffusible factors such as
      insulin-like growth factors (IGFs) capable of regulating epithelial cell growth
      in vitro, stromal cells were isolated by enzymatic digestion of rat intestine.
      Incorporation of [3H]thymidine into DNA and [14C]leucine into protein of IEC-6
      cells, a model intestinal epithelial cell line, was significantly increased (two-
      to threefold) when the IEC-6 cells were co-cultured with stromal cells, relative
      to IEC-6 cells grown alone. Medium conditioned by stromal cells stimulated DNA
      synthesis of IEC-6 cells in a dose-dependent manner. Analysis of the conditioned
      medium revealed that intestinal stromal cells secreted IGF-I, but little IGF-II,
      in addition to an M(r) 32,000 IGF-binding protein (IGFBP-2) and an IGFBP having
      M(r) approximately 24,000. We conclude that rat intestinal stromal cells secrete
      one or more diffusible factors, which may include IGF-I and IGFBPs, capable of
      stimulating proliferation of IEC-6 cells in vitro.

PMID- 9539959
TI  - In vitro antiviral activity on dengue virus of marine natural products.
AB  - Metabolites isolated from marine invertebrates, callipeltin A, crambescidin,
      ptilomycalin A, celeromycalin, gymnochrome B, gymnochrome D and isogymnochrome D
      previously shown bioactive on either herpes simplex virus 1 or human
      immunodeficiency virus, were tested on a new in vitro bioassay using the dengue
      virus 1. Only gymnochrome D and isogymnochrome D isolated from the living fossil
      crinoid Gymnocrinus richeri are highly potent dengue antiviral agents.

PMID- 9539960
TI  - NMR structures of the C-terminal end of human complement serine protease C1s.
AB  - Synthetic peptides derived from the C-terminal end of the human complement serine
      protease C1s were analysed by circular dichroism and nuclear magnetic resonance
      (NMR) spectroscopy. Circular dichroism indicates that peptides 656-673 and 653
      673 are essentially unstructured in water and undergo a coil-to-helix transition
      in the presence of increasing concentrations of trifluoroethanol. Two-dimensional
      NMR analyses performed in water/trifluoroethanol solutions provide evidence for
      the occurrence of a regular alpha-helix extending from Trp659 to Ser668 (peptide
      656-673), and from Tyr656 to Ser668 (peptide 653-673), the C-terminal segment of
      both peptides remaining unstructured under the conditions used. Based on these
      and other observations, we propose that the serine protease domain of C1s ends in
      a 13-residue alpha-helix (656Tyr-Ser668) followed by a five-residue C-terminal
      extension. The latter appears to be flexible and is probably locked within C1s
      through a salt bridge involving Glu672.

PMID- 9539961
TI  - Bioassay for hamster macrophage chemotaxis: application to study particle-lung
      interactions.
AB  - Attraction of lung macrophages to particle deposition sites has been demonstrated
      in different animal species. We reported a threefold increase of the number of
      macrophages to occur within 40 min after polystyrene particle deposition in
      hamster airways [Geiser et al. (1994) Am. J. Respir. Cell Mol. Biol. 160: 594
      603]. Complement-derived chemotactic activity is one of the mechanisms postulated
      for macrophage recruitment. It was the aim of this study to test whether
      complement-derived chemotactic activity is involved in the rapid recruitment of
      macrophages to the site of deposited polystyrene particles in hamster airways. We
      first developed an in vitro cell migration assay for hamster macrophages to
      assess complement-derived chemotaxis. Second, the bronchoalveolar lavage fluids
      (BALF) of four hamsters that had inhaled aerosols of polystyrene microspheres
      were tested for chemotactic activity by this bioassay and compared with BALF of
      four sham-exposed hamsters. Chemotactic response of macrophages was found toward
      complement-activated hamster serum, whereas macrophage migration was not
      increased toward BALF of particle and sham-exposed hamsters. In contrast,
      macrophage migration to BALF of both groups was reduced by 1.6-fold. Thus, the
      stimulus for macrophage recruitment to the site of deposited polystyrene
      particles in hamster airways could not be demonstrated using this bioassay.

PMID- 9539962
TI  - Regulation of Fas gene expression in HeLa cells as determined by modified RT-PCR.
AB  - We determined human Fas messenger RNA (mRNA) levels in HeLa cells using a
      'mutagenic' reverse transcription-polymerase chain reaction, which quantitates
      mRNA levels using the corresponding genomic DNA as an internal control. The
      expression level of Fas mRNA was very low in serum-deprived quiescent HeLa cells.
      In conjunction with the start of cell-cycle progression upon the addition of
      serum to culture medium, the Fas mRNA level gradually increased, reached its peak
      at 36 h and returned to the basal level after 48 h. HeLa cells at 36 h exhibiting
      a high level of Fas mRNA expression were more susceptible to the anti-Fas
      antibody apoptotic signal. Thus, the regulation of Fas expression is associated
      with cell-cycle progression, and this method for Fas mRNA detection may be
      useful, particularly for the analysis of small amounts of samples.

PMID- 9539963
TI  - Stimulation of uncoupling protein synthesis in white adipose tissue of mice
      treated with the beta 3-adrenergic agonist CGP-12177.
AB  - The effects of chronic treatment with the beta 3-adrenergic receptor agonist CGP
      12177 on uncoupling protein (UCP) synthesis in interscapular brown adipose tissue
      (IBAT), various white fat depots and skeletal muscle have been examined in the
      mouse (daily injection for 15 days at a dose of 0.5 mg/kg). The treatment
      increased the IBAT UCP content and led to the expression of UCP in inguinal white
      adipose tissue. The increase in IBAT UCP content took place in the absence of
      tissue hypertrophy, and despite the increase in total body UCP content, no
      changes in body weight were observed after the treatment. The results confirm
      that ectopic expression of UCP in non-BAT tissues can be induced after chronic
      adrenergic stimulation.

PMID- 9539964
TI  - Structural studies of a phosphatidyl serine-amorphous calcium phosphate complex.
AB  - A phosphatidyl serine-amorphous calcium phosphate complex has been synthesized as
      a model of the matrix vesicle system that is associated with the induction of
      mineral deposition in bone, cartilage and dentine. The complex has been studied
      using a novel technique of subtractive extended X-ray absorption fine structure
      (EXAFS). This enables spectra of the components of the molecules to be subtracted
      from the complex so as to identify the sites of interaction. The results suggest
      there is a movement in the nitrogen atom of the phosphatidyl serine which
      approaches the calcium atom in the mineral phase. This interpretation would link
      the membrane structure of the vesicle to the structure of the mineral in a way
      that could explain some of its roles in biomineralization.

PMID- 9539965
TI  - Sister chromatid exchanges in human lymphocytes treated in vitro with cadmium in
      G(o) and S phase of their cell cycles.
AB  - Sister chromatid exchanges (SCEs) were analyzed in human phytohemagglutinin
      activated peripheral lymphocyte cultures exposed to varying concentrations (10(
      7)-10(-3) M) of cadmium chloride in vitro at two different stages of the cell
      cycle, G(o) and early S phase. When cadmium chloride was administered at the G(o)
      phase, no increase in the SCEs were observed for the doses 10(-6) and 10(-5) M.
      Concentrations equal to or larger than 10(4) M cadmium chloride were lethal to
      human lymphocytes in our experimental conditions. A highly statistically
      significant increase was observed in the SCE frequency with increasing cadmium
      chloride concentration (10(-7)-10(-4)) when cadmium was administered at the early
      S phase, which was 24 h after culture initiation. The increase in SCE frequency
      was higher when the cultures were terminated at 54 h, compared to termination at
      72 h. In order to examine the effects of cadmium administered at the S phase on
      SCE frequency in different individuals, 10(-5) M concentration was used and the
      cultures were terminated at 54 h after culture initiation. A 2- to 3-fold
      increase in the SCE frequency was observed in all six individuals examined. A
      progressive decrease in the proliferative index was also observed by increasing
      cadmium chloride concentration. These results demonstrate that the genotoxicity
      of cadmium chloride may be changed depending on the stage of the cell cycle in
      human lymphocytes. This may be one of the reasons of contradictory findings in
      the literature.

PMID- 9539966
TI  - Comparison of responses of base-specific Salmonella tester strains with the
      traditional strains for identifying mutagens: the results of a validation study.
AB  - The ability of a TA7000 series of Salmonella his- mutant tester strains to detect
      mutagens as classified by the traditional tester strains (TA100, TA98, TA1535,
      TA1537, TA97, TA102 and TA104) was evaluated using 30 coded chemicals, 5 of which
      were duplicates with different code numbers. The TA7000 series of tester strains
      were TA7001, TA7002, TA7003, TA7004, TA7005 and TA7006, each of which reverts by
      a specific base substitution. In addition, each chemical was tested in a mixture
      of the base-specific strains (the Mix), plus the traditional strains, TA98 and
      TA1537. A liquid version of the Salmonella mutagenicity assay was performed in
      microtiter plates to allow partial automation for increased throughput. The
      results were compared to those in the National Toxicology Program (NTP) database,
      which were obtained from the traditional strains in the preincubation assay. In
      the two strains common to both protocols, TA98 and TA1537, the agreement was 80%
      and 85%, respectively. When compared to the NTP results for TA100, the Mix gave a
      72% concordance, while the addition of the frameshift tester strain, TA98,
      increased the agreement to 76%. The overall agreement on positive or negative
      classifications of mutagenicity was 88% for the 25 chemicals tested. There were
      three notable exceptions to the overall agreement. Benzaldehyde was detected as a
      mutagen in TA7005 in contrast to its classification as a non-mutagen in the NTP
      database. This does not necessarily contradict the NTP results because the base
      specific strains may respond to different mutagens. Two weak mutagens in the NTP
      database, 1-chloro-2-propanol and isobutyl nitrite, were not detected as mutagens
      in the base-specific new strains in the liquid protocol. While there are a number
      of major differences in the two assays, it was concluded that the results from
      each procedure are comparable.

PMID- 9539967
TI  - In vivo and in vitro induction of sister-chromatid exchanges by
      nordihydroguaiaretic acid.
AB  - Nordihydroguaiaretic acid (NDGA) is a phenolic lignan previously used as an
      antioxidant in commercial products, and with a number of properties potentially
      useful to man. As its genotoxic capacity has been poorly evaluated, in this
      investigation we determined its effect on the production of sister-chromatid
      exchanges (SCEs), and on the level of mitotic index (MI) in cultured human
      lymphocytes and in mouse bone marrow cells in vivo. The proliferative index (PI),
      and the average generation time (AGT) were also determined for human lymphocytes
      and in mouse bone marrow cells respectively. The in vitro study was made in two
      donors using NDGA doses of 1.1, 3.6, 6.7, 13.5, and 27.0 microM; and for the in
      vivo study the tested doses were 8.8, 17.6, 35.3, and 70.7 mg/kg of body weight.
      The results concerning SCE induction in human lymphocytes showed a dose-dependent
      response with a maximum mean increase of 5.52 SCE in relation to the control
      level, and with respect to MI and PI a decrement of more than 50% and a cell
      cycle delay was detected only with the high dose. In the study with bone marrow
      cells, a statistically significant difference was determined with the high two
      doses (an increase of 1.06 SCEs with 70.7 mg/kg in relation to the control
      level). The MI decreased only with the high dose and no modification was observed
      with respect to AGT. In conclusion, in both used models the study demonstrated
      that NDGA produced genotoxic and cytotoxic effects.

PMID- 9539968
TI  - Laser pyrolysis products: sampling procedures, cytotoxic and genotoxic effects.
AB  - The use of lasers in medical applications has grown enormously in the last few
      years. Recent chemical analysis of the laser pyrolysis products revealed that
      aerosols generated by pyrolytic decomposition of tissue could be health hazards.
      Therefore we analysed the genotoxic and mutagenic effects of laser pyrolysis
      products from different types of porcine tissue. The tissues were irradiated with
      a surgical CO2 laser and the generated aerosols were sampled as particulate
      fractions as well as low and highly volatile fractions. Then human leukocytes
      were incubated with the pyrolysis products and subjected to the comet assay. The
      results of the comet assay indicated the pyrolysis products being inducers of DNA
      damage. The ability to induce genotoxic effects turned out to be strongly
      dependent on the type of tissue that had been irradiated during laser treatment.
      To check whether the pyrolysis products also have mutagenic properties the
      Salmonella mutagenicity assay was performed. The particulate aerosol fractions of
      skin, muscle tissue and liver tissue clearly proved to be mutagenic in TA98 in
      the presence of S9 mix. There was no mutagenic effect detectable without
      metabolic activation. In conclusion, our experiments showed that the laser
      pyrolysis products originating from porcine tissues induced very potent genotoxic
      as well as mutagenic effects and therefore they could be potential health hazards
      for humans.

PMID- 9539969
TI  - Organ-specific genotoxicity of the potent rodent bladder carcinogens o-anisidine
      and p-cresidine.
AB  - We used a modification of the alkaline single-cell gel electrophoresis (SCG)
      (Comet) assay to evaluate the in vivo genotoxicity of two potent rodent bladder
      carcinogens, o-anisidine and p-cresidine, in mouse liver, lung, kidney, brain,
      and bone marrow, and in the mucosa of stomach, colon, and bladder. Male CD-1 mice
      (8 weeks old) were sacrificed 3 and 24 h after oral administration of o-anisidine
      at 690 mg/kg or p-cresidine at 595 mg/kg. Both chemicals were dissolved in olive
      oil. Both chemicals yielded statistically significant DNA damage in bladder
      mucosa 3 and 24 h after treatment. o-Anisidine yielded DNA damage in the colon at
      3 h, but not at 24 h. No significant effects were observed in any other organs.
      Our results suggest the importance of the urinary bladder as a sentinel organ for
      evaluating chemical genotoxicity in rodents.

PMID- 9539970
TI  - In vivo mutagenesis by the hepatocarcinogen quinoline in the lacZ transgenic
      mouse: evidence for its in vivo genotoxicity.
AB  - Quinoline is carcinogenic to the liver of rats and mice and mutagenic to
      bacterial tester strains in the presence of rat liver microsomal enzymes. The
      unscheduled DNA synthesis (UDS) study suggested that quinoline might be a non
      genotoxic carcinogen because of the lack of UDS-inducing capacity. In order to
      determine whether or not cancer induction is initiated by mutagenic DNA lesions,
      the present study was undertaken to evaluate the mutagenicity of quinoline in an
      in vivo mutation assay system using the lac Z transgenic mouse (Muta Mouse).
      Mutation was only induced in the liver, the target organ of carcinogenesis by
      quinoline, but not in the other organs examined, i.e. lung, kidney and spleen.
      Mutant frequency in the liver was 4-fold higher than in the untreated control
      animals. Dimethylnitrosamine, used as a positive control, induced mutation at a
      frequency 5-fold higher in the liver and 3-fold higher in the spleen than in
      their respective control organs. It can be concluded that the genotoxicity of
      quinoline is responsible for its hepatocarcinogenesis, although UDS was not
      induced under the conditions previously reported.

PMID- 9539971
TI  - Studies on the effect of the solvents dimethylsulfoxide and
      ethyleneglycoldimethylether on the mutagenicity of four types of diisocyanates in
      the Salmonella/microsome test.
AB  - The mutagenicity of isomers and homologs of diphenylmethanediisocyanate (4,4'
      diisocyanatodiphenylmethane, 2,4'-diisocyanatodiphenylmethane, a mixture of
      monomeric MDI isomers, and polymeric MDI), containing 55-100% of monomeric MDI,
      was determined in the Salmonella/microsome test using dimethylsulfoxide (DMSO)
      and ethyleneglycoldimethylether (EGDE) as solvents. Positive results were
      obtained for DMSO solutions of all four diisocyanates in the presence of S9 mix
      containing 30% S9 fraction. Uniformly negative results were found when the
      diisocyanates were dissolved in EDGE. These results correspond to those of
      analytical investigations. A small amount of diaminodiphenylmethane (MDA) is one
      of the reaction products formed when MDI is dissolved in commercial DMSO. No MDA
      could be detected in solutions of MDI in EGDE. It is therefore concluded that the
      positive results obtained with diisocyanates in DMSO solutions are due to the
      formation of MDA. This is artificially formed through the hydrolysis of MDI,
      caused by traces of water that are always present in DMSO. These findings
      indicate that DMSO is an inappropriate solvent and should therefore not be used
      in any in vitro study with diisocyanates. EGDE may be a suitable replacement. The
      positive test results reported so far for DMSO solutions of MDI are thus only of
      limited relevance for risk evaluation.

PMID- 9539972
TI  - Determination of HPRT mutant frequency and molecular analysis of T-lymphocyte
      mutants derived from coke-oven workers.
AB  - We measured the frequency of mutant (MF) lymphocytes at the hprt locus in a
      population of 43 coke-oven workers exposed to PAH and in a group of 26 non
      exposed workers. A non-significant increase in MF in the exposed group (19.0 +/-
      16.3) compared to the non-exposed group (15.8 +/- 14.6) was observed. Moreover,
      when we considered smoking habits for the overall population, the MF values were
      higher, although not significantly, in smokers than in non-smokers. For some T
      cell mutant clone structural alterations, splicing and coding errors were
      detected by PCR-based methods. We analysed 161 HPRT- clones, derived from exposed
      and non-exposed workers by multiplex-PCR and 56 HPRT- clones by reverse
      transcriptase-PCR. Overall, the percentages of the different types of gene
      alterations were similar in exposed and non-exposed subjects. Only the frequency
      of splice mutations in mutant clones derived from coke-oven workers was higher
      (22%) than in non-exposed donors (11%).

PMID- 9539973
TI  - Evaluation of the genotoxic properties of paraquat in V79 Chinese hamster cells.
AB  - The genotoxic potential of the herbicide paraquat (PQ), an intracellular
      generator of superoxide, was comparatively tested in various genotoxicity tests
      with V79 Chinese hamster cells. PQ clearly induced cytotoxicity and chromosome
      aberrations but did not induce gene mutations at the HPRT locus or increased DNA
      migration in the comet assay under the same treatment conditions. Using a
      modified comet assay protocol with formamidopyrimidine-DNA glycosylase (FPG)
      protein, a DNA repair enzyme which specifically nicks DNA at sites of 8-oxo
      guanines and formamidopyrimidines, we could not detect oxidative DNA base damage
      after PQ treatment. When cells were treated directly on the slides after lysis
      (i.e, after the cell membrane barrier was eliminated), increased DNA migration
      was observed after treatment with high PQ-concentrations. Our results suggest
      that PQ does not significantly induce DNA lesions relevant for HPRT gene
      mutations in cultivated V79 cells. Since PQ-induced chromosome aberrations only
      occur after treatment with high concentrations which totally prevent cell
      survival and are not preceded by an induction of DNA strand breakage in intact
      cells, their biological significance has to be questioned.

PMID- 9539974
TI  - Risk assessment in cervical dysplasia patients by single cell gel electrophoresis
      assay: a study of DNA damage and repair.
AB  - Precancerous lesions of cervix, commonly known as dysplasia, present a complex
      problem because of their biological behavior. Increased genetic instability,
      either inherent or induced by some external mutagen, is considered as a primary
      event or a predisposing factor to neoplastic transformation. The relationship
      between genetic instability and susceptibility towards cervical cancer was
      evaluated with the comet or single cell gel electrophoresis (SCGE) assay. Among
      precancerous individuals, genomic instability was observed in cervical epithelial
      cells and peripheral blood leukocytes. The mean basal DNA damage and mean
      susceptibility to DNA damage by the mutagen (MNNG) treatment increased whereas
      repair capacity decreased with progression of the disease in a stepwise manner.
      Inter and intra individual variability was maximum in cancerous group. Risk was
      estimated by giving a predictive value for each precancerous individual. In
      combination with morphological, biochemical, and cytogenetic parameters, the SCGE
      assay may serve as a novel tool to predict the fate of cervical dysplasia.

PMID- 9539975
TI  - Thiopronin reduces the frequencies of neocarzinostatin-induced chromosomal
      aberrations and sister chromatid exchanges in Chinese hamster ovary cells.
AB  - Chinese hamster ovary (CHO) cells were treated in the G1 phase of the cell cycle
      with different concentrations of neocarzinostatin (NCS) alone or in combination
      with N-(2-mercaptopropionyl)-glycine (thiopronin; TP). TP reduces the frequencies
      of NCS-induced chromosomal aberrations (CA) and of sister chromatid exchanges
      (SCE) significantly when added to the cultures simultaneously (TPsim), 1 min
      (TP1) or 10 min (TP10) after the addition of NCS. The addition of TP 30 min
      (TP30) or 60 min (TP60) after NCS reduces the frequencies of SCE, but not of CA.
      Our results indicate that the induction of CA and SCE by NCS is partially based
      on different mechanisms.

PMID- 9539976
TI  - Structure and function of mammalian DNA ligases.
AB  - DNA joining events are required for the completion of DNA replication, DNA
      excision repair and genetic recombination. Five DNA ligase activities, I-V, have
      been purified from mammalian cell extracts and three mammalian LIG genes, LIG1
      LIG3 and LIG4, have been cloned. During DNA replication, the joining of Okazaki
      fragments by the LIG1 gene product appears to be mediated by an interaction with
      proliferating cell nuclear antigen (PCNA). This interaction may also occur during
      the completion of mismatch, nucleotide excision and base excision repair (BER).
      In addition, DNA ligase I participates in a second BER pathway that is carried
      out by a multiprotein complex in which DNA ligase I interacts directly with DNA
      polymerase beta. DNA ligase III alpha and DNA ligase III beta, which are
      generated by alternative splicing of the LIG3 gene, can be distinguished by their
      ability to bind to the DNA repair protein, XRCC1. The interaction between DNA
      ligase III alpha and XRCC1, which occurs through BRCT motifs in the C-termini of
      these polypeptides, implicates this isoform of DNA ligase III in the repair of
      DNA single-strand breaks and BER. DNA ligase II appears to be a proteolytic
      fragment of DNA ligase III alpha. The restricted expression of DNA ligase III
      beta suggests that this enzyme may function in the completion of meiotic
      recombination or in a postmeiosis DNA repair pathway. Complex formation between
      DNA ligase IV and the DNA repair protein XRCC4 involves the C-terminal region of
      DNA ligase IV, which contains two BRCT motifs. This interaction, which stimulates
      DNA joining activity, implies that DNA ligase IV functions in V(D)J recombination
      and non-homologous end-joining of DNA double-strand breaks. At the present time,
      it is not known whether DNA ligase V is derived from one of the known mammalian
      LIG genes or is the product of a novel gene.

PMID- 9539977
TI  - Extrachromosomal unequal homologous recombination and gene conversion in simian
      kidney cells: effects of UV damage.
AB  - Shuttle plasmid vectors containing the SV40 origin of replication and tandem neo
      genes with distally placed non-overlapping deletions were used to study the
      effects of DNA damage on extrachromosomal homologous recombination in simian
      kidney cells. DNA was introduced into COS7 cells by a lipofectin-mediated
      transfection procedure and recombination was assessed by analyzing the structure
      of plasmids. Recombinational events observed included unequal homologous
      recombination (triplication), gene conversion, double reciprocal recombination,
      deletion (pop-outs), gene amplification (4-6 copies), and multimerization.
      Triplication, an event that previously had not been reported in association with
      extrachromosomal recombination, predominated in experiments with undamaged
      vectors. The recombination frequency (NeoR/AmpR) of vectors randomly damaged by
      UV irradiation was essentially unchanged; however, the relative number of
      triplication events decreased significantly. Selective damage in one of the two
      neo genes increased the relative frequency of gene conversion. The experimental
      system developed for use in this study detects all major homologous recombination
      events observed in chromosomal direct repeat sequences in mammalian cells and
      yeast and should prove valuable for future studies of homologous recombination in
      mammalian cells.

PMID- 9539978
TI  - Seasonal variation of DNA damage and repair in patients with non-melanoma skin
      cancer and referents with and without psoriasis.
AB  - Quadruples of skin cancer patients with and without psoriasis and referents with
      and without psoriasis (4 x 20 study persons) were identified and examined for DNA
      damage by single cell gel electrophoresis (comet-assay) and DNA-repair by UV
      induced unscheduled DNA synthesis (UDS) in mononuclear blood cells (lymphocytes
      and monocytes). DNA damage (strand breaks and alkaline labile sites) as assessed
      by the comet assay and DNA repair as assessed by UDS were significantly
      associated with the season in which blood sampling took place. This variation
      might be explained by an increased exposure to solar radiation. When the comet
      tail moment data were stratified by sampling period, an interaction between
      psoriasis and skin cancer was detected, with patients with psoriasis and skin
      cancer exhibiting more DNA damage. Patients with psoriasis and skin cancer also
      had lower UDS compared to healthy study persons, suggesting that the more DNA
      damage may be caused by a lower rate of DNA repair. In all study persons, the
      extent of UDS correlated positively with the amount of DNA damage determined by
      the comet assay.

PMID- 9539979
TI  - A single N-2-acetylaminofluorene adduct alters the footprint of T7 (exo-) DNA
      polymerase bound to a model primer-template junction.
AB  - Bovine pancreatic deoxyribonuclease I (DNaseI) has been used to footprint T7 (exo
      ) DNA polymerase bound to a model primer-template junction. The polymerase was
      blocked at a specific position either by the omission of dCTP from the reaction
      mix or by the presence of a N-(deoxyguanosin-8-yl)-2-acetylaminofluorene (dGuo
      AAF) adduct. This lesion has been shown to be a severe block for several DNA
      polymerases, both in in vitro primer elongation experiments, and during the in
      vivo replication of AAF-monomodified single-stranded vectors. The footprints
      obtained with unmodified primer-template DNA define two protected domains
      separated by an inter-region that remains sensitive to DNaseI, and several
      hypersensitive sites located on both strands. Binding of the polymerase to AAF
      monomodified duplexes results in the same protection pattern as that obtained
      with the unmodified duplexes. However, the hypersensitive sites either disappear
      or are dramatically reduced. The results suggest that the AAF lesion alters the
      correct positioning of the duplex DNA within the polymerase cleft.

PMID- 9539980
TI  - Modification of enzyme sulfhydryl groups suppresses UV-induced mutagenesis
      depending on the nucleotide excision repair system in Escherichia coli B/r WP2.
AB  - S-Methyl methanethiosulfonate (MMTS), which was isolated from cauliflower
      (Brassica oleracea var. botrytis) homogenate as a potent bio-antimutagen, has
      been used as an enzyme-sulfhydryl (SH) temporary blocking agent in modification
      studies of enzyme activities. We examined whether 23 kinds of MMTS-related
      compounds have a suppressing effect on UV mutagenesis in Escherichia coli B/r
      WP2. Disulfide derivatives of diphenyl, 2.2'-dipyridine and 4.4'-dipyridine, and
      N-ethyl maleimide (NEM), which temporarily or tightly block sulfhydryl (SH)
      groups, showed similar suppressing effect in E. coli B/r WP2, but not in WP2s hcr
      (uvrA-) in the range of nanomolar/plate as MMTS previously did. Cystamine
      sulfate, methyl methylsulfinylmethyl sulfide and S-methyl-L-cysteinesulfoxide
      moderately suppressed, and diallyl disulfide and glutathione (oxidized form)
      weakly suppressed UV mutagenesis in E. coli B/r WP2 in the range of
      micromolar/plate. MMTS and phorone, a glutathione (GSH)-depleting agent, lowered
      the intracellular GSH level in E. coli B/r WP2, but phorone did not inhibit UV
      induced mutation. These results indicate that the target for SH-modification is
      enzyme-SHs but not GSH, and that the direct or indirect modification of enzyme
      activity by SH-blocking might be involved in the antimutagenesis through a
      pathway associated with the DNA-excision repair system.

PMID- 9539981
TI  - Generation and characterization of an immortal cell line of xeroderma pigmentosum
      group E.
AB  - Xeroderma pigmentosum group E (XP-E) fibroblasts (XP95TO) were transformed with
      pSV3neo. Selection in medium containing G418 yielded 14 clones with extended life
      span. Following crisis, one clone was recovered that behaved in culture as an
      immortal cell line and was named XPET6/1. Expression of the SV40 large T antigen
      gene (Tag) and increased level of p53 were demonstrated by western analyses.
      Fingerprinting with 14 polymorphic microsatellite genetic markers confirmed that
      XPET6/1 originated from the parental strain XP95TO. XPET6/1 retained the
      sensitivity to killing by UV observed with the parental strain. Cell-free
      extracts from the immortal or the parental XP-E cells were deficient in excision,
      compared to extracts from HeLa or extracts from Tag-transformed XP variant
      fibroblasts. Complementation of XP-E extracts with XP-A, XP-D or XP-G extracts
      restored nucleotide excision activity to normal levels. XPET6/1 could prove a
      useful cell line for cloning of the XPE gene by functional complementation.

PMID- 9539982
TI  - Search for DNA repair pathways in Drosophila melanogaster.
AB  - The knowledge about the existence of different pathways for the repairing of DNA
      lesions has made possible a better understanding of mutation processes. The
      double mutant method has been shown to be useful for grouping rad mutants in
      yeast. Through this method, three different groups of repair mechanisms were
      found: (a) RAD3 group corresponding to the excision repair of UV lesions, (b)
      RAD6 group corresponding to the translesion type of post-replication repair and
      (c) RAD52 group corresponding to the recombination type of post-replication
      repair. In this work, a search for a classification of Drosophila mus mutants in
      groups analogous to yeast RAD groups is done. Information obtained by double
      mutant studies was integrated with that obtained by biochemical, recombination,
      DNA damaging agent sensitivity and mutation studies. The following groups were
      found: (a) group of mei9 and mus201, analogous to RAD3, (b) group of mei41 and
      mus302 analogous to RAD52 and, (c) group of mus104 and mus101 analogous to RAD6.
      In addition, there are mutants that belong to a group corresponding to pre
      replication repair of MMS lesions such as mus103, mus306 and mus207. As a
      peculiarity of Drosophila, it was found that interaction between pre- and post
      replication repair mechanisms is indifferent and not synergistic as was found in
      yeast. A possible explanation could be a weaker control of post-replication
      repair mechanisms in Drosophila than in yeast. It is expected that this research
      could help for a better understanding of repair mechanisms in complex organisms.

PMID- 9539983
TI  - Slicing the pie. Correlating HbA--values with average blood glucose values in a
      pie chart form.
AB  - OBJECTIVE: The purpose of this study was to define the correlation between HbA1c
      values and the percentage of home blood glucose (HBG) measurements within given
      ranges in a pie chart in three age-groups of subjects with type 1 diabetes.
      RESEARCH DESIGN AND METHODS: HbA1c values were compared with HBG measurements in
      subjects who did at least three blood glucose tests per day over 30 days in three
      age groups: 5-11, 12-16, and 17-35 years. The blood glucose values were
      arbitrarily divided into three groups, defined as the percentage of HBG
      measurements within, above, and below target range. Each range was then compared
      with the corresponding HbA1c value. Longitudinal data were also collected for 279
      of the subjects after a mean of 139 days. RESULTS: A strong correlation (P =
      0.001) was found between HbA1c values and the average blood glucose, and also
      with the percentage of HBG measurements within, above, and below target range in
      each of the three age-groups (P < 0.001). Analyses of longitudinal data showed a
      strong correlation of the changes in HbA1c values to the changes in blood glucose
      values. CONCLUSIONS: These data showed that a pie-shaped graph of the HBG data
      can be useful as a clinical parameter in helping patients and families attain
      desired HbA1c values.

PMID- 9539984
TI  - Offering a randomized trial of intensive therapy for IDDM to adolescents. Reasons
      for refusal, patient characteristics, and recruiter effects.
AB  - OBJECTIVE: To identify reasons adolescents refuse to participate in a randomized
      trial of intensive therapy (IT) for IDDM, to describe the patient characteristics
      of those who consent and those who refuse to participate, and to examine
      recruiter effects on trial participation rates. RESEARCH DESIGN AND METHODS: A
      total of 99 adolescents, age 11-18 years, were provided with the results of the
      Diabetes Control and Complications Trial and approached for possible study
      participation by two nurse recruiters. Adolescents refusing the trial were
      administered a semi-structured interview to describe reasons for study refusal;
      responses were recorded and later coded into categories. Patient characteristics
      of consenters and refusers were collected and compared. The differential
      enrollment rates of the two nurse recruiters were also compared. RESULTS: A total
      of 56 patients (approximately 57%) agreed to participate; 43 refused. The four
      most common reasons for study refusal were 1) increased clinic visits (42%), 2)
      increased insulin injections (30%), 3) increased frequency of self-monitoring of
      blood glucose (SMBG) (28%), and 4) transportation difficulties (19%). Concerns
      about randomization to an unwanted treatment condition and fears of hypoglycemia
      or weight gain were rarely cited. Consenters and refusers did not differ in
      demographic characteristics, disease status, or family composition. Large
      differences were found between the two nurse recruiters: one experienced a 60%
      refusal rate, while the other experienced a 27% refusal rate. CONCLUSIONS: Issues
      of convenience (increased clinic visits, transportation difficulties) and
      concerns about the demands of IT (increased injections and SMBG) were the
      predominant reasons for trial refusal. Patient characteristics did not
      differentiate consenters from refusers. However, recruiters differed greatly in
      study refusal rates, suggesting that provider behavior may be an important but
      understudied aspect of adolescent acceptance of randomized trials in general and
      IT in particular.

PMID- 9539985
TI  - Estimation of the glomerular filtration rate in NIDDM patients from plasma
      creatinine concentration after cimetidine administration.
AB  - OBJECTIVE: Glomerular filtration rate (GFR) can be estimated in patients with
      renal disease from plasma creatinine concentration, age, sex, and body weight
      according to the formula of Cockcroft and Gault. The hypothesis that this method
      can be improved when tubular secretion of creatinine is inhibited by cimetidine
      was studied in NIDDM patients. RESEARCH DESIGN AND METHODS: In 30 outpatients
      with NIDDM and normo- (n = 10), micro- (n = 9), or macroalbuminuria (n = 11), GFR
      was measured as the urinary clearance during continuous infusion of 125I-labeled
      iothalamate. Plasma creatinine concentration was analyzed with an enzymatic assay
      before and after 800 mg t.i.d. oral cimetidine was given during a 24-h period.
      RESULTS: Plasma creatinine rose in all patients after cimetidine administration
      and, as a consequence, the clearance calculated with the Cockcroft-Gault formula
      fell. The ratio of this formula and GFR decreased from 1.16 +/- 0.20 to 0.97 +/-
      0.16 (means +/- SD). This ratio tended to be smaller in the normo- (0.93) than in
      the micro- (0.98) and macroalbuminuric (1.00) groups. Also, 20 patients with a
      BMI < 30 kg/m2 had a smaller ratio than those with a BMI > 30 kg/m2 (0.92 vs.
      1.07; P < 0.05). Bland and Altman analysis showed a difference of the Cockcroft
      Gault formula and GFR of 12.0 +/- 17.4 ml.min-1 (1.73 m2)-1, which decreased to 
      3.8 +/- 14.8 ml.min-1.(1.73 m2)-1. The same analysis of 24-h creatinine clearance
      with urine collection and GFR showed larger standard deviations. CONCLUSIONS: GFR
      can be estimated in an acceptable way from plasma creatinine concentration after
      cimetidine administration in outpatients with NIDDM. Despite a nonsignificant
      underestimation in normoalbuminuric and overestimation in overweighted patients,
      this method is superior to 24-h creatinine clearance with outpatient urine
      collection.

PMID- 9539986
TI  - U-shaped and J-shaped relationships between serum insulin and coronary heart
      disease in the general population. The Bruneck Study.
AB  - OBJECTIVE: To evaluate the relationship existing between serum insulin and
      coronary heart disease (CHD) in the general population. RESEARCH DESIGN AND
      METHODS: In a cross-sectional survey on atherosclerosis and its risk factors, 500
      men and 500 women aged 40-79 years were randomly selected from the population of
      Bruneck, Italy. Clinical, biochemical, and behavioral risk factors of
      atherosclerosis were assessed in the 936 subjects who participated in the study.
      Serum insulin was measured at fasting (n = 888) and 2 h (n = 811, known diabetic
      subjects were excluded) after an oral glucose load. CHD was ascertained by an
      abnormal electrocardiogram and/or a history of angina or myocardial infarction.
      RESULTS: Subjects were stratified according to serum insulin quintiles at fasting
      or 2 h after glucose loading. After adjustment for sex, age, BMI, smoking,
      physical activity, alcohol intake, and socioeconomic status (analysis of
      covariance), cardiovascular risk factors clustered in subjects of the top insulin
      quintile. Multiple logistic regression analysis, including sex and age in model
      1, sex, age, BMI, glucose tolerance, socioeconomic status, and behavioral
      variables in model 2, or this set of variables together with triglycerides and
      apoproteins A1 and B, fibrinogen, and blood pressure status in model 3, revealed
      a significant association between high serum insulin and CHD when median insulin
      quintile was used as the reference class. Moreover, low serum insulin levels,
      such as those found in subjects of the lowest quintile, were independently
      related to CHD. These results were found either before (model 1) or after (models
      2 and 3) adjusting for several covariates. Consistent results were found in men
      and women, as well as in younger and older subjects. CONCLUSIONS: Results of the
      present study suggest that both hyperinsulinemia and "hypoinsulinemia" are
      independent indicators of CHD. Furthermore, it is proposed that the relationship
      between CHD and fasting insulin is U-shaped, whereas that between CHD and
      postglucose insulin may be J-shaped.

PMID- 9539987
TI  - Hospitalization and mortality of diabetes in older adults. A 3-year prospective
      study.
AB  - OBJECTIVE: In light of increased fatality from acute events and the increased
      frequency of chronic complications, life expectancy might well be shortened in
      older patients with diabetes. The current studies investigated factors affecting
      the likelihood of dying or being hospitalized in older patients with diabetes.
      RESEARCH DESIGN AND METHODS: A total of 135 older patients with diabetes were
      followed for 3 years after predictive factors were evaluated and compared with a
      cohort of patients without diabetes. RESULTS: Mortality was only 3,250 per
      100,000 patient-years, similar to that for patients without diabetes, but the
      frequency of hospitalizations was more than twice as high in patients with
      diabetes. Five factors predicted hospitalization and death. Of these, the
      geriatric depression score was the best predictor of these poor outcomes.
      CONCLUSIONS: Older patients with diabetes were hospitalized more often than those
      without diabetes, but mortality was similar. Dysphoria is a major predictor of
      poor outcomes in older patients with diabetes.

PMID- 9539988
TI  - Self-rated health and diabetes of long duration. The Wisconsin Epidemiologic
      Study of Diabetic Retinopathy.
AB  - OBJECTIVE: To evaluate the self-reported quality of life in individuals with
      diabetes of long duration. RESEARCH DESIGN AND METHODS: An interview was
      administered 14 years after baseline to two cohorts of individuals with diabetes
      who have been followed in an epidemiological study periodically since 1980.
      Responses to the Medical Outcomes Study Short Form 36 as related to complications
      of diabetes, age, glycosylated hemoglobin level, and other characteristics were
      assessed. RESULTS: Physical function, physical role, general health scales, and a
      general question about health were related to diabetes characteristics in older-
      and younger-onset individuals. Symptoms of sensory neuropathy were associated
      with the four measures in both younger- (n = 645) and older-onset (n = 292)
      individuals. Other descriptive variables in the younger-onset group were the
      presence of nephropathy, cardiovascular disease, smoking, peak expiratory flow,
      physical activity, and glycosylated hemoglobin. Hypoglycemic reactions were of
      only borderline significance and that for only one scale (physical role). In
      older-onset individuals, cardiovascular disease, physical activity, and sex were
      descriptive of responses to the quality-of-life questions. CONCLUSIONS: Factors
      related to diabetes contribute to self-assessed health. some of these factors may
      be modifiable, which, if altered, may lead to improved quality of life.

PMID- 9539989
TI  - Family environment, glycemic control, and the psychosocial adaptation of adults
      with diabetes.
AB  - OBJECTIVE: To evaluate whether the family system variables of adults with
      diabetes relate to the adequacy of metabolic control or the psychosocial
      adaptation to the illness. RESEARCH DESIGN AND METHODS: A total of 150 insulin
      requiring adults were assessed on a single occasion. They completed two family
      system measures (the Family Environment Scale [FES] and the Diabetes Family
      Behavior Checklist [DFBC]), two quality-of-life measures (the Diabetes Quality of
      Life Scale and the Medical Outcomes Study Health Survey-36), and one measure of
      cognitive appraisal (the Appraisal of Diabetes Scale). Glycemic control was
      assessed using HbA1c results. Demographic data (age, sex, diabetes type, duration
      of diabetes, and number of diabetes-related medical complications) were gathered
      from the patients' charts. RESULTS: Concerning glycemic control, none of the
      family system measures were significant predictors of HbA1c. Older age and longer
      duration of diabetes predicted higher HbA1c values. For psychosocial adaptation,
      when family members behaved in ways that supported the diabetes care regimen
      (measured by the DFBC), the individual with diabetes was more satisfied with his
      or her adaptation to the illness and reported less interference in role function
      due to emotional problems. Family cohesion (measured by the FES) also related to
      better physical function. Women reported higher levels of diabetes satisfaction.
      The Appraisal of Diabetes Scale predicted glycemic control and psychosocial
      adaptation. CONCLUSIONS: For insulin-treated adults with diabetes, family system
      variables do not relate to glycemic control, but they do relate to psychosocial
      adaptation. Future work should explore the impact of family-centered
      interventions on adaptation, sex differences in adaptation, and the use of the
      Appraisal of Diabetes Scale as a first-line clinical screening tool.

PMID- 9539990
TI  - Unrecognized diabetes among hospitalized patients.
AB  - OBJECTIVE: To evaluate the hospital care rendered to hyperglycemic individuals
      who did not have a diagnosis of diabetes before admission. RESEARCH DESIGN AND
      METHODS: A total of 1,034 consecutively hospitalized adult patients at a 750-bed
      inner-city teaching hospital were evaluated. Patients with one or more plasma
      glucose values > 200 mg/dl were identified by the laboratory data system on a
      daily basis. Patients without a diagnosis of diabetes at the time of admission
      were evaluated to determine if and how physicians addressed the hyperglycemia,
      whether a new diagnosis of diabetes was made during admission, and whether follow
      up was planned to address the hyperglycemia. RESULTS: After excluding patients
      who were admitted for a primary diagnosis of diabetes, 37.5% of all hyperglycemic
      medical patients and 33% of hyperglycemic surgical patients were without a
      diagnosis of diabetes at the time of admission. These patients had a mean peak
      glucose of 299 mg/dl, and 66% had two or more elevated values during their
      hospitalization. Fifty-four percent received insulin therapy, and 59% received
      bedside glucose monitoring, yet 66% of daily patient progress notes failed to
      comment on the presence of hyperglycemia or diabetes. Diabetes was documented in
      only three patients (7.3%) as a possible diagnosis in the daily progress notes.
      CONCLUSIONS: Despite marked hyperglycemia, most medical records made no reference
      to the possibility of unrecognized diabetes. Given the average delay of a decade
      between the onset and diagnosis of type 2 diabetes, further evaluation of
      hyperglycemic hospitalized patients may present an important opportunity for
      earlier detection and the initiation of therapy.

PMID- 9539991
TI  - Gender, autoantibodies, and obesity in newly diagnosed diabetic patients aged 40
      75 years.
AB  - OBJECTIVE: To evaluate the frequency of autoimmune markers (islet cell antibodies
      (ICA] and glutamic acid decarboxylase antibodies [GADA]) and clinical features in
      newly diagnosed people with diabetes aged 40-75 years. RESEARCH DESIGN AND
      METHODS: Two hundred fifty-nine consecutive patients (aged 40-75 years) with
      newly suspected diabetes diagnosed during a 2-year period were studied. The
      diagnosis of newly discovered diabetes was confirmed in 203 patients. Gender,
      BMI, HbA1c, fasting C-peptide, ICA, and GADA were evaluated. The frequency of
      obesity was estimated using two different sets of criteria: 1) National Diabetes
      Data Group (NDDG) criteria, and 2) criteria based on a Swedish reference
      population. RESULTS: The annual incidence of diabetes was 106 per 100,000 people.
      The incidence of diabetes in those patients who were 40-54 years old was
      significantly higher in men than in women (odds ratio: 2.16; P = 0.001). ICA were
      detected in 16 of 203 patients (8%), whereas 17 of 203 patients (8%) were GADA+;
      10 of 203 (5%) patients were positive for both ICA and GADA. Among the 203
      diabetic patients, 19 (9.4%) were classified as having IDDM, giving an IDDM
      incidence of 10 per 100,000 people aged 40-75 years. The frequency of obesity in
      NIDDM was high but varied with its definition; the frequency of obesity was
      highest (P < 0.001) when NDDG criteria, and not Swedish reference values, were
      used (57 of 75 [76%] vs. 40 of 75 [53%] for women and 66 of 109 [61%] vs. 45 of
      109 [41%] for men). CONCLUSIONS: A striking male preponderance was found among
      incident cases of diabetes in people aged 40-54 years. Autoimmune markers were
      detected in 10% of incident cases of diabetes in people aged 40-75 years. Using a
      conservative estimation, as many as 10 of 100,000 middle-aged and elderly
      subjects developed IDDM. The frequency of obesity in NIDDM was high but this was
      also the case in the reference population.

PMID- 9539992
TI  - Effects of voglibose on glycemic excursions, insulin secretion, and insulin
      sensitivity in non-insulin-treated NIDDM patients.
AB  - OBJECTIVE: To investigate the effects of voglibose, an alpha-glucosidase
      inhibitor, on daily glycemic excursions, insulin secretion, and insulin
      sensitivity in non-insulin-treated NIDDM patients. RESEARCH DESIGN AND METHODS:
      An open prospective study was conducted in 27 NIDDM patients receiving diet
      therapy alone or treatment with a sulfonylurea drug. Of the study subjects, 14
      patients were treated with voglibose; the remaining 13 patients served as the
      control group. The metabolic parameters were evaluated before treatment and at
      week 4 of treatment as follows: glycemic excursions by M-value and 1,5-anhydro-D
      glucitol (1,5-AG), insulin secretion by area under the curve of daily serum
      insulin (AUCinsulin), and insulin sensitivity by the K index of the insulin
      tolerance test (KITT). RESULTS: After the study treatment, HbA1c and plasma
      glucose in the patients who had received voglibose were comparable to those of
      patients in the control group. M-value was lower in the patients treated with
      voglibose than in the control subjects (5.7 +/- 0.9 vs. 9.8 +/- 1.2, P < 0.05).
      1,5-AG was higher in the patients treated with voglibose than in the control
      subjects (12.2 +/- 1.0 vs. 8.2 +/- 0.7 micrograms/ml, P < 0.01). A statistically
      significant increase in AUCinsulin occurred after treatment with voglibose
      (2,223.5 +/- 390.6 to 1,546.7 +/- 303.4 pmol.l-1.h, P < 0.05), but no change
      occurred in the control group (2,364.5 +/- 315.4 to 2,464.2 +/- 269.3 pmol.l-1.h,
      P = 0.60). Insulin sensitivity (KITT) was improved to a statistically significant
      level in both the patients treated with voglibose and the patients in the control
      group. KITT in the patients after voglibose treatment was comparable to that of
      the control group (3.18 +/- 0.30 vs. 3.21 +/- 0.23%/min, P = 0.94). CONCLUSIONS:
      The results suggest that voglibose lowers the daily glycemic excursions and
      inhibits overwork of the pancreatic beta-cells but has little effect on insulin
      sensitivity in NIDDM patients.

PMID- 9539993
TI  - Biological variation of glycated hemoglobin. Implications for diabetes screening
      and monitoring.
AB  - OBJECTIVE: To assess the inherent potential of glycated hemoglobin as a screening
      test for type 2 diabetes by determining the biological variation in nondiabetic
      subjects. RESEARCH DESIGN AND METHODS: HbA1c values were measured by high
      performance liquid chromatography (HPLC) in 12 nondiabetic subjects (7 men and 5
      women; median age, 40 years [range, 21-55 years]) on 10 fortnightly occasions.
      The nondiabetic index of individuality (IOI) for HbA1c (i.e., the square root of
      the ratio of intra- to interindividual variance) was determined. Any test with an
      IOI of 1.4 has the most potential in disease screening, while one of 0.6 will be
      of little value. RESULTS: The analytical variance contributed to 9% of the total
      test variance, intraindividual variance, 6%; and interindividual variance, 85%.
      The IOI was, therefore, only 0.27. Thus, nondiabetic HbA1c values vary markedly
      between subjects, while values in the same individual change little with time. As
      such, to lie outside the assay reference range, the HbA1c values of some
      nondiabetic subjects must exceed 12 SD from their usual mean value, while in
      others a change of only 2 SD would be sufficient. CONCLUSIONS: This fundamental
      characteristic of HbA1c means that even if analytical methods improve, glycated
      hemoglobin measurements will always be of limited value when screening for type 2
      diabetes. If similar interindividual differences also exist in diabetic subjects,
      then patients with the same glycemic control may vary by at least 1-2%, which has
      implications in setting glycated hemoglobin targets.

PMID- 9539994
TI  - Evaluation of GHb assays in France by national quality control surveys.
AB  - OBJECTIVE: To evaluate the state of the art concerning GHb assays through
      analysis of a large-scale quality control survey and to compare the results with
      those of previous surveys. RESEARCH DESIGN AND METHODS: A lyophilized hemolyzate
      prepared from human erythrocytes containing a physiological HbA1c level (5.5%)
      was sent to 3,500 French laboratories in February of 1995 and assayed as a
      patient's sample under routine conditions. Distribution of values was analyzed
      from the reported results for each method. The results were compared with the
      assigned value (acceptable range: +/- 20%) and with the upper value of the
      reference range currently used. RESULTS: Results were obtained from 2,674
      laboratories, among which 39% used cation-exchange chromatography methods, 37.5%
      affinity chromatography, 16% immunological methods, and 7.5% electrophoresis. The
      number of laboratories using immunological methods increased from 100 to 400
      between 1993 and 1995. The overall interlaboratory coefficient of variation (CV)
      was 20.2%, with within-method CVs ranging between 3.2 and 29.5%. Method-to-method
      accuracy varied dramatically, with mean HbA1c values ranging from 4.4 to 8.2%.
      Results from 75% of the laboratories were comprised in the acceptable range; 88%
      of them reported a value within the normal range of the method used. CONCLUSIONS:
      The interlaboratory variability of results illustrates the difficulties
      encountered by diabetologists in the follow-up of diabetic patients using results
      obtained from different laboratories. It demonstrates the usefulness of the
      internationally developed standardization process of GHb measurements and points
      out the need for laboratories to fulfill good practices.

PMID- 9539995
TI  - Preserved endothelial function in IDDM patients, but not in NIDDM patients,
      compared with healthy subjects.
AB  - OBJECTIVE: To examine endothelial function (EF) noninvasively in IDDM and NIDDM
      patients with long diabetes duration. RESEARCH DESIGN AND METHODS: We studied EF
      in 17 IDDM patients without diabetic complications and in 25 NIDDM patients with
      comparable glycemic control and with diabetic complications and compared both
      with nondiabetic control subjects matched for age, sex, and lumen diameter. Using
      high-resolution ultrasound, we measured the endothelial-dependent (FAD%) and
      independent vasodilation (GTN%); the blood flow at rest, postocclusive, and after
      application of 400 micrograms glyceroltrinitrate of the branchial artery; and the
      intima media thickness (IMT) of the common carotid artery. RESULTS: In the IDDM
      patients, neither FAD% (8.2 +/- 4.6 vs. 7.6 +/- 4.2%), GTN% (16.3 +/- 4.9 vs.
      18.4 +/- 6.4%), nor postocclusive blood flow (40.6 +/- 19.1 vs. 39.3 +/- 23.6
      cm/s) differed from the control subjects. IMT (0.59 +/- 0.10 vs. 0.55 +/- 0.14
      mm) was slightly, but not significantly, elevated. In contrast, the NIDDM
      patients showed an impaired FAD% (3.8 +/- 3.3 vs. 6.9 +/- 4.4%, P < 0.01), no
      difference in GTN%, and a decreased postocclusive blood flow (18.5 +/- 13.8 vs.
      32.7 +/- 20.0 cm/s, P < 0.01). IMT was significantly increased in NIDDM patients
      (0.77 +/- 0.14 vs. 0.62 +/- 0.10 mm, P < 0.001). CONCLUSIONS: In contrast to
      NIDDM patients with cardiovascular complications, IDDM patients with long
      diabetes duration and good long-term metabolic control do not have impaired EF
      compared with control subjects.

PMID- 9539996
TI  - Insulin secretion in normal glucose-tolerant relatives of type 2 diabetic
      subjects. Assessments using hyperglycemic glucose clamps and oral glucose
      tolerance tests.
AB  - OBJECTIVE: To assess insulin secretion in normal glucose-tolerant Caucasian first
      degree relatives of type 2 diabetes subjects and in matched normal glucose
      tolerant control subjects and to compare insulin secretion as assessed using a
      hyperglycemic glucose clamp with insulin secretion as assessed using an oral
      glucose tolerance test (OGTT). RESEARCH DESIGN AND METHODS: Twenty-one first
      degree relatives of type 2 diabetic subjects and 21 control subjects without a
      family history of type 2 diabetes, who were matched for sex, age, BMI, waist-to
      hip ratio, and aerobic capacity, underwent a hyperglycemic glucose clamp (10
      mmol/l, 180 min). An OGTT (75 g glucose in 300 ml water) was also performed.
      RESULTS: First-phase insulin release (plasma insulin, 0-10 min) was not different
      (multiple analysis of variance [MANOVA]: F = 2.63, P = 0.11). Second-phase
      insulin release was lower (MANOVA: F = 4.18, P = 0.047). Separate analyses of
      variance showed decreased plasma insulin levels from 120 min onward (all P <
      0.05), decreasing to geometric mean (95% CI) levels of 330 (270-402) and 462 (366
      582) pmol/l at 180 min in relatives and control subjects, respectively. The
      insulin sensitivity index (ISI) as assessed using a hyperglycemic clamp was not
      different between the two groups. Mean +/- SE ISI during the 3rd hour was 27.5 +/
      2.2 and 30.5 +/- 3.0 micrograms.kg-1.min-1.pmol-1.l-1 in relatives and control
      subjects, respectively (P > 0.20). At 90 min after the OGTT, log plasma insulin
      levels correlated significantly with second-phase insulin release as assessed
      using the hyperglycemic glucose clamp. CONCLUSIONS: Normal glucose-tolerant first
      degree relatives of type 2 diabetic subjects have a decreased second-phase
      insulin release, compared with matched control subjects. After an OGTT, 90-min
      values of log plasma insulin and 90-min values of the ratio of log plasma insulin
      to blood glucose may be good indicators of insulin secretory properties in normal
      glucose-tolerant family members of type 2 diabetic subjects.

PMID- 9539997
TI  - Effects of glycemic control on protective responses against hypoglycemia in type
      2 diabetes.
AB  - OBJECTIVE: To determine the effects of glycemic control on the counterregulatory
      responses to hypoglycemia in type 2 diabetes. RESEARCH DESIGN AND METHODS: Seven
      poorly controlled type 2 diabetes patients (mean HbA1c, 11.3 +/- 1.1%) were
      studied by stepped hyperinsulinemic hypoglycemic clamp (nadir, 2.4 mmol/l) before
      and after improving glycemic control with insulin treatment. Counterregulatory
      hormones, symptoms, and four-choice reaction time were measured at each glucose
      plateau. RESULTS: In patients with poorly controlled type 2 diabetes,
      counterregulatory hormone responses began at higher plasma glucose levels than
      did those in healthy subjects (epinephrine, 4.4 +/- 0.2 vs. 3.7 +/- 0.2 mmol/l, P
      = 0.011). After significant improvement in glycemic control (mean HbA1c, 8.1 +/-
      0.9%, P < 0.001) was achieved without severe hypoglycemia, hormonal responses
      started at much lower plasma glucose levels (e.g., epinephrine, 3.5 +/- 0.3
      mmol/l, P = 0.005) and were significantly reduced in magnitude (e.g., area under
      epinephrine response curve, 306 +/- 93 vs. 690 +/- 107 nmol.min-1.l-1, P =
      0.012). This was accompanied by a change in the plasma glucose threshold at which
      hypoglycemic symptoms first developed from 3.6 +/- 0.2 to 3.0 +/- 0.2 mmol/l (P =
      0.019). In contrast, the plasma glucose threshold at which four-choice reaction
      time deteriorated did not change significantly (3.1 +/- 0.1 vs. 2.9 +/- 0.1
      mmol/l, P = 0.125). CONCLUSIONS: Counterregulatory responses begin at
      normoglycemia in poorly controlled type 2 diabetes. Improving glycemic control
      with insulin therapy normalizes hormonal responses but lowers the plasma glucose
      levels at which hypoglycemic symptoms develop to levels associated with
      impairment of four-choice reaction time, a marker of cognitive function. This
      process potentially increases the risk of severe hypoglycemia, but to a lesser
      extent than occurs in type 1 disease.

PMID- 9539998
TI  - The association between diabetic complications and exercise capacity in NIDDM
      patients.
AB  - OBJECTIVE: Exercise capacity has been used as a noninvasive parameter for
      predicting cardiovascular events. It has been demonstrated previously in NIDDM
      patients that several risk factors (i.e., obesity, smoking, hypertension, and
      African-American race) are associated with an impaired exercise capacity. We
      studied 265 male and 154 female NIDDM patients who underwent graded exercise
      testing with expired gas analyses to determine the possible influences of
      diabetic neuropathy, nephropathy, and retinopathy on exercise capacity. RESEARCH
      DESIGN AND METHODS: Univariate and multiple linear regression analyses were
      performed to determine the relationship between diabetic neuropathy, urinary
      albumin excretion (UAE), and retinopathy with respect to peak oxygen consumption
      (VO2). Neuropathy was assessed by neurological symptom and disability scores,
      autonomic function testing, and quantitative sensory exams involving thermal and
      vibratory sensation. Three categories of UAE were used: normal albuminuria (< 20
      micrograms/min), microalbuminuria (20-200 micrograms/min), and overt albuminuria
      (> 200 micrograms/min). Retinopathy was assessed by stereoscopic fundus
      photographs. Multiple linear regression analyses were then performed controlling
      for age, sex, length of diagnosed diabetes, duration of hypertension, race and
      ethnicity, GHb, BMI, and smoking to determine whether there was an independent
      effect of these diabetic complications on exercise capacity. RESULTS: Univariate
      analyses revealed that the presence of diabetic retinopathy (P = 0.03),
      neuropathy (P = 0.002), microalbuminuria (P = 0.04), and overt albuminuria (P =
      0.06) were associated with a lower peak VO2. Multiple linear regression analyses
      were performed to determine independent relationships with peak VO2. The results
      revealed that increasing retinopathy stage (Parameter estimate [PE] = -0.59 +/-
      0.3 ml.kg-1.min-1; P = 0.026) and increasing UAE stage (PE = -0.62 +/- 0.3 ml.kg
      1.min-1; P = 0.04) were associated with a decrease in peak VO2. CONCLUSIONS: In
      the present study of NIDDM subjects, a significant independent association was
      demonstrated between diabetic nephropathy and retinopathy with exercise capacity.
      These results were obtained controlling for age, sex, length of diagnosed
      diabetes, hypertension, race, and BMI. Thus the findings in this large NIDDM
      population without a history of coronary artery disease indicate a potential
      pathogenic relationship between microvascular disease and exercise capacity.

PMID- 9539999
TI  - Economic consequences of diabetes mellitus in the U.S. in 1997. American Diabetes
      Association.
AB  - OBJECTIVE: Diabetes is a significant public health problem resulting in
      substantial morbidity and mortality. The objectives of this study were 1) to
      determine the direct medical and indirect costs attributable to diabetes and 2)
      to calculate total and per capita expenditures of people with and without
      diabetes. RESEARCH DESIGN AND METHODS: Direct medical and indirect expenditures
      attributable to diabetes in 1997 were estimated at $98 billion. Medical
      expenditures for the treatment of diabetes were estimated for all individuals in
      the U.S. in 1997 by age-group, sex, race, type of condition, and site of service.
      Productivity costs due to disability and premature mortality were also estimated
      for selected patient cohorts. Etiological fractions based on national health care
      survey data and published literature were used to estimate the proportion of
      health service utilization and mortality associated with diabetes-related chronic
      complications and general medical conditions. RESULTS: Direct medical
      expenditures attributable to diabetes in 1997 totaled $44.1 billion and comprised
      $7.7 billion for diabetes and acute glycemic care, $11.8 billion due to the
      excess prevalence of related chronic complications, and $24.6 billion due to the
      excess prevalence of general medical conditions. The majority of attributable
      expenditures were for inpatient care (62%), followed by outpatient services (25%)
      and nursing home care (13%). Two-thirds of all medical costs for diabetes were
      borne by elderly people. Attributable indirect costs totaled $54.1 billion and
      comprised $17.0 billion resulting from premature mortality and $37.1 billion from
      disability. Total medical expenditures incurred by people with diabetes totaled
      $77.7 billion or $10,071 per capita, compared with $2,669 for people without
      diabetes. CONCLUSIONS: The economic burden of diabetes mellitus in the U.S. is
      enormous. Medical innovations that can delay the onset and slow the progression
      of diabetes have tremendous potential to mitigate the associated clinical and
      cost repercussions.

PMID- 9540000
TI  - Consensus Development Conference on Insulin Resistance. 5-6 November 1997.
      American Diabetes Association.

PMID- 9540001
TI  - American Diabetes Association annual meeting, 1997, and the Teczem Consultant
      Meeting. Diabetic nephropathy.

PMID- 9540003
TI  - Hyperglycemia and coronary heart disease.

PMID- 9540002
TI  - Cifenline succinate and dementia in an elderly NIDDM patient.

PMID- 9540004
TI  - Diabetic mastopathy. A frequent source of confusion with lobular breast
      carcinoma.

PMID- 9540005
TI  - Methylene tetrahydrofolate reductase gene, dietary folate, NIDDM, and
      atherosclerosis in Canadian Oji-Cree.

PMID- 9540011
TI  - Efficacy of diet and exercise in reducing body weight and conversion to overt
      diabetes.

PMID- 9540006
TI  - Carotid arterial intimal-medial thickening and plaque formation in NIDDM.

PMID- 9540007
TI  - General practitioners are the most important conveyors of information to their
      patients regarding diabetic retinopathy.

PMID- 9540008
TI  - Local adverse events associated with long-term treatment by implantable insulin
      pumps. The French EVADIAC Study Group experience. Evaluation dans le Diabete du
      Traitement par Implants Actifs.

PMID- 9540009
TI  - Increased hydrogen peroxide formation in polymorphonuclear leukocytes of IDDM
      patients.

PMID- 9540010
TI  - Is there a glycemic threshold for mortality risk?

PMID- 9540012
TI  - Variation of postprandial plasma glucose, palatability, and symptoms associated
      with a standardized mixed test meal versus 75 g oral glucose.
AB  - OBJECTIVE: To compare within-subject variability of plasma glucose measured 2 h
      after a glucose tolerance test (GTT) with that of plasma glucose measured 2 h
      after administration of a standardized test meal (diabetes screening product
      [DSP], Ceapro, Edmonton, Alberta, Canada) and to determine the relationship
      between the two sets of plasma glucose measurements. RESEARCH DESIGN AND METHODS:
      Plasma glucose and insulin responses of 36 overnight-fasted subjects (10 lean
      normal, 9 obese normal, 9 with impaired glucose tolerance [IGT], and 8 with mild
      diabetes) were studied on eight different mornings after they consumed 75 g oral
      glucose or 50 g carbohydrate from the DSP. Each test meal was repeated four times
      by each subject. Within-subject coefficients of variation (CVs) (CV = 100 x
      SD/mean) of plasma glucose concentrations 2 h after administration of the GTT and
      DSP were compared by repeated measures ANOVA and linear regression analysis.
      RESULTS: Mean plasma glucose 2 h after administration of the DSP (D) was linearly
      related to that 2 h after the GTT (G): G = 1.5 x D - 1.6 (r = 0.97, P < 0.0001).
      The CV of 2-h plasma glucose was significantly lower after administration of the
      DSP, 10.5 +/- 1.0%, than after the GTT, 12.7 +/- 1.18% (P = 0.025). The effect of
      test meal on CV differed in different groups of subjects (P = 0.018), with the
      largest difference found in IGT subjects, in whom the CV after DSP administration
      was 47% less than after the GTT (P = 0.0005). The DSP was significantly more
      palatable and produced fewer adverse symptoms than the GTT. CONCLUSIONS: Plasma
      glucose concentrations measured 2 h after DSP administration are closely related
      to those measured 2 h after the GTT but are more consistent than the 2-h post-GTT
      concentrations within the critical IGT range. This finding suggests that
      measurement of plasma glucose 2 h after administration of the DSP may allow more
      precise discrimination among normal glucose levels, IGT, and diabetes than
      measurement of plasma glucose 2 h after the GTT.

PMID- 9540013
TI  - Well-being, cerebral function, and physical fatigue after nocturnal hypoglycemia
      in IDDM.
AB  - OBJECTIVE: This study assessed the effect of nocturnal hypoglycemia on well-being
      cerebral function, and physical fatigue the next day in 10 subjects with IDDM.
      RESEARCH DESIGN AND METHODS: After an exercise test to determine work-loads
      corresponding to 30 and 60% VO2max, volunteers were studied twice, 4 weeks apart.
      Blood glucose was lowered one night to 2.3-2.7 mmol/l for 1 h, and at the control
      visit, hypoglycemia was avoided. The next morning, well-being was assessed using
      the minor symptom evaluation profile (MSEP), and cerebral function was assessed
      with the paced auditory serial addition test, the digit symbol substitution test,
      trail making part B, four-choice reaction time, and auditory P300 latency.
      Subjects then exercised at predetermined workloads corresponding to 30% VO2max
      for 30 min and 60% VO2max until exhaustion. Fatigue was assessed every 10 min
      using the Borg scale for rating of perceived exertion. RESULTS: All three
      components of the MSEP scored higher (indicating more symptoms) after the
      hypoglycemic night compared with the control night (P < 0.01 contentment, sleep;
      P < 0.001 vitality). None of the cerebral function tests performed the next day
      was affected by hypoglycemia. Exercise capacity was similar at both visits, but
      subjects were more fatigued after the hypoglycemic night (P < 0.01, analysis of
      variance). There were no differences in potassium, catecholamine, glucose, or
      lactate concentrations between visits either before or during exercise.
      CONCLUSIONS: One hour of hypoglycemia at night affects a subject's sense of well
      being, but not cerebral function, the next day. The greater fatigue after the
      hypoglycemic night cannot be explained by the biochemical parameters measured.

PMID- 9540014
TI  - The relationship of menstrual irregularity to type 2 diabetes in Pima Indian
      women.
AB  - OBJECTIVE: Menstrual irregularity is associated with hyperinsulinemia and
      hyperandrogenemia in nondiabetic Pima Indian women of child-bearing age. In this
      population-based study, we determined the relationship of menstrual irregularity
      to type 2 diabetes in Pima Indian women. RESEARCH DESIGN AND METHODS:
      Participants for this cross-sectional analysis were 695 nonpregnant Pima Indian
      women, aged 18-44 years, involved in an ongoing epidemiologic study of diabetes
      among residents of the Gila River Indian Community of Arizona. Clinical data were
      collected by questionnaire and an examination that included a 75-g oral glucose
      tolerance test; diabetes was diagnosed by World Health Organization criteria.
      Menstrual irregularity was defined as an interval of 3 months or more between
      menses, when not pregnant, since age 18 years. RESULTS: History of menstrual
      irregularity was significantly associated with a high prevalence of diabetes (37
      vs. 13%; odds ratio = 4.2, 95% CI = 1.6-10.8) in the least obese women (BMI < 30
      kg/m2), adjusted for the effects of age and overall obesity. This association
      was, in part, because of greater central obesity in women with irregular menses.
      In more obese women, there was little association with menstrual irregularity,
      and diabetes was frequent regardless of menstrual history. CONCLUSIONS:
      Prevalence of type 2 diabetes is higher among Pima indian women with a history of
      menstrual irregularity. The difference is most pronounced among the least obese
      group of women. This association may be because of insulin resistance and
      hyperinsulinemia, which predict type 2 diabetes, also causing hyperandrogenism
      and menstrual irregularity. The findings reinforce the need to evaluate women
      with menstrual irregularity for hyperglycemia.

PMID- 9540015
TI  - Lifestyle intervention in overweight individuals with a family history of
      diabetes.
AB  - OBJECTIVE: To assess the effect of lifestyle intervention over 2 years on changes
      in weight, coronary heart disease (CHD) risk factors, and incidence of diabetes
      in overweight individuals with a parental history of diabetes. RESEARCH DESIGN
      AND METHODS: Participants (n = 154), who were 30-100% over ideal body weight, had
      one or both parents with diabetes, and were currently nondiabetic, were randomly
      assigned to 2-year treatments focused on diet (decreasing calories and fat
      intake), exercise (goal of 1,500 kcal/week of moderate activity), or the
      combination of diet plus exercise or to a no-treatment control group. Subjects
      were reassessed at 6 months, 1 year, and 2 years. RESULTS: At 6 months, the
      groups differed significantly on measures of eating, exercise, and fitness;
      weight losses in the diet and diet-plus-exercise groups were significantly
      greater than in the exercise and control conditions. Weight losses were
      associated with positive changes in CHD risk factors. After 6 months, there was
      gradual deterioration of behavioral and physiological changes, so that at 2
      years, almost no between-group differences were maintained. Differences between
      groups in risk of developing diabetes were of borderline significance (P = 0.08).
      Strongest predictors were impaired glucose tolerance at baseline, which was
      positively related to risk of developing diabetes, and weight loss from baseline
      to 2 years, which was negatively related; in all treatment groups, a modest
      weight loss of 4.5 kg reduced the risk of type 2 diabetes by approximately 30%
      compared with no weight loss. CONCLUSIONS: Although initially successful, the
      interventions studied here were not effective in producing long-term changes in
      behavior, weight, or physiological parameters. However, weight loss from 0 to 2
      years reduced the risk of developing type 2 diabetes. Since modest weight loss
      significantly reduced risk of type 2 diabetes, further research is needed to
      determine how best to increase the percentage of subjects achieving at least a
      modest weight loss.

PMID- 9540017
TI  - Diabetes prevalence and hospital and pharmacy use in the Veterans Health
      Administration (1994). Use of an ambulatory care pharmacy-derived database.
AB  - OBJECTIVE: To develop a diabetes registry from an outpatient pharmacy database to
      systematically analyze the prevalence of diabetes, patterns of glycemic
      medication and glucose monitoring, pharmacy costs, and hospital use related to
      diabetes care in the Veterans Health Administration (VHA) in fiscal year (FY)
      1994. RESEARCH DESIGN AND METHODS: Veterans with diabetes were identified using a
      software program that extracted the social security number (SSN) of patients
      receiving insulin, sulfonylurea agents, or glucose-monitoring supplies. The
      cumulative FY94 cost for a drug was calculated by multiplying the units dispensed
      times the unit cost for each fill, using the actual drug cost that was in effect
      at the time of dispensing. Admission data were obtained by crossmatching the SSN
      registry with the VHA Austin Mainframe Patient Treatment Files to retrieve
      associated diagnosis-related groups (DRG), Physicians' Current Procedural
      Terminology (CPT), and International Classification of Diseases, 9th revision,
      Clinical Modification (ICD-9-CM) codes. RESULTS: From among 1,180,260 unique
      patients, 139,646 veterans with diabetes receiving insulin, oral agents, or
      glucose-monitoring strips were identified, accounting for a prevalence of 11.83%
      from 62 Veterans Administration medical centers. There were 63,078 individuals
      (52%) who received oral agents, of whom 26.3% also received blood glucose
      monitoring supplies; 46,664 individuals (39%) received insulin, of whom 53.2%
      received blood glucose-monitoring supplies; and 9,440 individuals (8%) received
      both oral agents and insulin during FY94, with 64.4% receiving blood glucose
      monitoring supplies. Only 1,482 (1.2%) individuals received monitoring supplies
      alone, and 129 patients (0.1%) were provided with an insulin pump. Using an
      adjusted data set, 12% of veterans accounted for 24% of all outpatient pharmacy
      costs, with an average expenditure of $622 for veterans with diabetes compared
      with $276 for veterans without diabetes. There was $454 (73%) for non-diabetes
      specific prescriptions and $168 (27%) for prescriptions related to glycemic
      control. Of pharmacy expenditures for glycemic control, $101 (60.1%) was
      attributed to insulin, oral agents, and supplies, while $67 (39.9%) was
      attributable to glucose monitoring. Veterans with diabetes were admitted 1.6
      times as frequently as veterans without diabetes. CONCLUSIONS: This study
      demonstrates the feasibility of using a pharmacy-based electronic diabetes
      database in a payor system that can track both claims and individual classes of
      medication based on a unique identifier number. While the prevalence of diabetes
      in the VHA is high relative to other health care systems and the general
      population, patterns of medication usage, pharmacy costs, and relative admission
      frequency are comparable to results from the private sector.

PMID- 9540016
TI  - High blood glucose concentration is a risk factor for mortality in middle-aged
      nondiabetic men. 20-year follow-up in the Whitehall Study, the Paris Prospective
      Study, and the Helsinki Policemen Study.
AB  - OBJECTIVE: To assess the association between high but nondiabetic blood glucose
      levels and the risk of death from all causes, coronary heart disease (CHD),
      cardiovascular disease, and neoplasms. RESEARCH DESIGN AND METHODS: We studied
      the 20-year mortality of non-diabetic, working men, age 44-55 years, in three
      European cohorts known as the Whitehall Study (n = 10,025), the Paris Prospective
      Study (n = 6,629), and the Helsinki Policeman Study (n = 631). These men were
      identified by their 2-h glucose levels following an oral glucose tolerance test
      and by the absence of a prior diagnosis of diabetes. As the protocol for the oral
      glucose tolerance test and methods for measuring glucose differed between
      studies, mortality was analyzed according to the percentiles of the 2-h and
      fasting glucose distributions, using the Cox's proportional hazards model.
      RESULTS: Men in the upper 20% of the 2-h glucose distributions and those in the
      upper 2.5% for fasting glucose had a significantly higher risk of all-cause
      mortality in comparison with men in the lower 80% of these distributions, with
      age-adjusted hazard ratios of 1.6 (95% CI 1.4-1.9) and 2.0 (1.6-2.6) for the
      upper 2.5%. For death from cardiovascular and CHD, men in the upper 2.5% of the 2
      h and fasting glucose distributions were at higher risk, with age-adjusted hazard
      ratios for CHD of 1.8 (1.4-2.4) and 2.7 (1.7-4.4), respectively. CONCLUSIONS: If
      early intervention aimed at lowering blood glucose concentrations can be shown to
      reduce mortality, it may be justified to lower the levels of both 2-h and fasting
      glucose, which define diabetes.

PMID- 9540021
TI  - Prescription drug use and costs among diabetic patients in primary health care
      practices in Germany.
AB  - OBJECTIVE: To evaluate drug prescriptions and costs among diabetic patients in
      primary care practices in Germany. RESEARCH DESIGN AND METHODS: Computerized data
      on prescriptions and costs (drug company sales prices) were analyzed in 30,604
      diabetic and 17,723 (5% random sample) nondiabetic patients from 362 primary care
      practices during 1994. Relative use ratios for drug groups were obtained from
      logistic regression models (odds ratio [OR] for diabetes) controlling for age,
      sex, and other covariates. Relative costs (diabetic:nondiabetic) were estimated
      by direct age and sex standardization. RESULTS: Diabetic patients had an
      increased prescription use for most drugs. A substantial increased use (OR > or =
      1.4) was found for cardiovascular drugs, fibrates, gout medication, laxatives,
      and wound care products. Diabetic subjects (7.9% of all patients) accounted for
      21% of total annual prescription costs in the practices. Total costs (U.S.
      dollars) per patient-year were threefold higher (diabetic patients $384; control
      subjects $123). After excluding antidiabetic agents and age- and sex
      standardization, relative costs were still 1.5 times higher (P < 0.05). Diabetes
      treatment accounted for 24% of total costs in diabetic patients (insulin 12%;
      oral antidiabetics 6%). The most important cost factor was cardiovascular drugs
      (CVDs) (39%). Three CVD groups accounted for about 50% of total CVD costs in
      diabetic patients (ACE inhibitors 25%; Ca-antagonists 16%; nitrates 10%).
      CONCLUSIONS: Prescription use among diabetic patients in primary health care
      practices was predominantly increased for cardiovascular drugs and for treatment
      of diabetes-associated disorders. Diabetic patients accounted for over one-fifth
      of the total pharmacy costs in primary practices, indicating that diabetes is a
      major economic factor in drug use.

PMID- 9540018
TI  - Transient improvement in glycemic control. The impact of pregnancy in women with
      IDDM.
AB  - OBJECTIVE: Good glycemic control throughout pregnancy in patients with diabetes
      is of paramount importance but often appears to deteriorate in the postpartum
      period. The aim of this study was to ascertain the timing of the improvement in
      glycemic control associated with pregnancy in women with IDDM and to examine
      changes in glycemic control after delivery. RESEARCH DESIGN AND METHODS:
      Peripartum glycemic control was assessed in a retrospective study of 30 women
      with IDDM whose age was 28 +/- 6 years (means +/- SD) and whose diabetes duration
      was 14 +/- 6 years. RESULTS: Mean total HbA1 fell incrementally from a peak at 2
      3 years preconception to a nadir between 24 weeks and term, only to return to
      preconception levels within a year after delivery. Of the 30 women, 15 (50%)
      attained an HbA1 in the nondiabetic range for pregnancy at some point during
      their pregnancy, and 7 (23%) women achieved this by 24 weeks gestation. Women
      with an HbA1 > 9% at booking had a significantly higher HbA1 at 0-6 and 6-12
      months preconception, and throughout pregnancy their HbA1 was significantly
      higher. After delivery, attendance rates at routine diabetes review clinics were
      low, with 11% of women not attending for longer than 24 months. CONCLUSIONS:
      Nearly all women with IDDM can achieve near normoglycemia during pregnancy,
      irrespective of previous glycemic control, although those with high HbA1 levels
      at booking are less likely to achieve this. After delivery, glycemic control
      deteriorates. Efforts to improve glycemic control should be intensified in the
      preconception period and maintained after delivery. The poor postpartum
      attendance at diabetes clinics requires specific action.

PMID- 9540019
TI  - Neuropsychological complications of IDDM in children 2 years after disease onset.
AB  - OBJECTIVE: To compare the neuropsychological profiles of children with IDDM with
      a community control group at two time points: 3 months after disease onset and 2
      years after the baseline assessment. RESEARCH DESIGN AND METHODS: A total of 123
      children (age 3-14 years) with recent IDDM onset were compared with 129 community
      control subjects, stratified for age and sex, on standardized measures of general
      intelligence, attention, speed of processing, memory, learning, executive skills,
      and behavioral adjustment soon after diagnosis and 2 years later. Exclusion
      criteria were premorbid evidence of central nervous system disease or trauma, or
      English not spoken in the home. RESULTS: There were no differences between
      children with IDDM and control subjects on any measure at the initial assessment
      3 months after disease onset. Two years later, children with IDDM tended to show
      a less positive change, relative to control subjects, in their standardized
      scores on measures of general intelligence, and significantly so on the
      vocabulary (P < 0.01) and block design (P < 0.05) subtests. Multivariate group
      differences were also apparent on speed of processing (P < 0.05) and learning (P
      < 0.01) subtests, reflecting smaller developmental gains in the children with
      IDDM when compared with control subjects. CONCLUSIONS: The findings are
      consistent with previous reports, suggesting that IDDM is associated with an
      increased risk of mild neuropsychological dysfunction. The skills most affected
      in this cohort were information processing speed, acquisition of new knowledge,
      and conceptual reasoning abilities. Clinicians and educators should be made aware
      of the risk of specific neuropsychological deficits in children with IDDM.

PMID- 9540029
TI  - Gastric emptying delay and gastric electrical derangement in IDDM.
AB  - OBJECTIVE: Patients with diabetes can develop gastrointestinal motor
      complications; however, prevalence of gut dysmotility in children with diabetes
      is poorly understood. We measured gastric emptying time and gastric electrical
      activity in children with IDDM; presence of dyspeptic symptoms was also assessed.
      RESEARCH DESIGN AND METHODS: Gastric emptying time and gastric electrical
      activity were measured by ultrasonography and electrogastrography (EGG),
      respectively, in 40 consecutive IDDM children (median age: 9 years [6-14])
      without autonomic neuropathy; 15 healthy children (median age: 7 years [4-15])
      served as control subjects. The EGG variables studied were percent of electrical
      dysrhythmias (bradygastria or 0.5-2.0 cpm, tachygastria or 4.0-9.0 cpm; normal
      rhythm is 2.0-4.0 cpm) and fed-to-fasting ratio of the dominant EGG power. Blood
      glucose level in the fasting state and 180 min after feeding and HbA1C
      concentration were also measured. Data are given as median (ranges) and means +/-
      SD. Statistical analysis was performed using the parametric t test and the
      nonparametric signed-rank tests, with P < 0.05 considered significant. RESULTS:
      Gastric emptying time was delayed in 26 patients (group A), whereas in 14
      patients (group B), it was in the same range as control values; group A patients
      significantly differed from group B for increased prevalence of gastric
      electrical dysrhythmias (P < 0.01) and for a lower fed-to-fasting ratio of the
      dominant EGG power (P < 0.01). Group B patients did not differ from control
      subjects for the EGG variables measured. Diabetic children with gastroparesis had
      significantly higher levels of both HbA1C and blood glucose measured 180 min
      after feeding than those with normal gastric emptying time (P < 0.05); there was
      a significant correlation between levels of HbA1C and degree of gastric emptying
      delay, whereas a significant inverse correlation between gastric emptying time
      and fed-to-fasting ratio of the dominant EGG power was found both in patients and
      control subjects. CONCLUSIONS: Delay of gastric emptying time and gastric
      electrical abnormalities are found in a high proportion of children with diabetes
      and can contribute to poor glycemic control, most likely by causing a mismatch
      between the onset of insulin action and the delivery of nutrients into the small
      intestine. Diabetic children with unexplained poor glycemic control should be
      investigated for abnormalities in gastric motility.

PMID- 9540030
TI  - Advances toward the implantable artificial pancreas for treatment of diabetes.
AB  - Recent research on development of the implantable artificial pancreas for
      treatment of diabetes is reviewed, based on a Medline literature search that
      focused on glucose sensors, insulin pumps, and pump control systems. To achieve a
      closed feedback loop, a clinically applicable implantable artificial pancreas
      requires miniaturization and coordination of three components: an insulin pump, a
      blood glucose monitor, and a control system. Recent clinical studies have
      demonstrated that implantable insulin pumps are feasible for satisfactory control
      of diabetes for over a year, with the major complication being obstruction of the
      infusion catheter. Research on continuous glucose sensors has predominantly used
      the glucose-oxidase reaction or near-infrared light spectroscopy. Implantable
      glucose oxidase sensors have been limited by local factors causing unstable
      signal output, whereas optical sensors must overcome interference by substances
      with absorption spectra similar to glucose. Investigators have developed control
      algorithms in an effort to stabilize operation of the integrated artificial
      pancreas in the face of variations in sensor output and pump function. The
      ultimate goals of fully automatic glucose control by an artificial pancreas
      include prevention or delay of chronic complications of diabetes, lowered risk of
      hypoglycemia, and less patient inconvenience and discomfort than with multiple
      daily glucose self-tests and insulin injection. The recent developments of
      optical glucose sensing, radiotelemetry systems to link pump and sensor, and
      miniaturization and refinement of insulin pumps are significant steps toward a
      clinically applicable artificial pancreas.

PMID- 9540022
TI  - Cognitive function in an elderly population with persistent impaired glucose
      tolerance.
AB  - OBJECTIVE: To study cognitive function in an elderly population with persistent
      impaired glucose tolerance (IGT). RESEARCH DESIGN AND METHODS: Fasting and
      postload 2-h plasma glucose and insulin levels were determined at baseline in a
      population-based sample of 1,300 people and repeated an average of 3.5 years
      later in 980 subjects. At follow-up, cognitive function was evaluated in subjects
      with persistent normal glucose tolerance (NGT; n = 506) and IGT (n = 80) with a
      brief neuropsychological test battery. RESULTS: Subjects with persistent IGT
      scored lower in the Mini-Mental State Examination (MMSE) and in the Buschke
      Selective Reminding Test long-term memory scores. Multiple linear regression
      analysis revealed that age, education, and insulin levels (either fasting or 2-h
      value) were associated with the MMSE score in subjects with persistent IGT. Other
      potential risk factors for impaired cognitive function were not significantly
      associated with the MMSE score. CONCLUSIONS: Our study showed that persistent IGT
      in the elderly is associated with mildly impaired cognitive function, and
      hyperinsulinemia may account for this association.

PMID- 9540023
TI  - Longitudinal changes in pancreatic beta-cell function and metabolic clearance
      rate of insulin in pregnant women with normal and abnormal glucose tolerance.
AB  - OBJECTIVE: To evaluate basal pancreatic beta-cell secretion and suppression
      during infused insulin and the metabolic clearance rate of insulin in women with
      normal and abnormal glucose tolerance prior to conception and during pregnancy.
      RESEARCH DESIGN AND METHODS: Seven women with normal glucose tolerance and nine
      women with abnormal glucose tolerance during gestation were evaluated prior to
      conception, in early (12-14 weeks) and late (34-36 weeks) gestation. Basal
      insulin and C-peptide were measured after an 11-h fast and during the last 40 min
      of a 2-h hyperinsulinemic-euglycemic clamp at 40 mU.m-2.m-1. Suppression of basal
      C-peptide was calculated as the steady-state C-peptide/basal C-peptide. The
      metabolic clearance rate of insulin was calculated by dividing the insulin
      infusion rate by the steady-state insulin concentration, which was corrected for
      residual beta-cell secretion. RESULTS: No significant differences were noted in
      the following parameters between women with normal and abnormal glucose tolerance
      with advancing gestation: increase in basal insulin (P = 0.20) and C-peptide (P =
      0.12), ability of infused insulin to decrease basal C-peptide concentration (P =
      0.22), and metabolic clearance rate of insulin (P = 0.76). There was a
      significant 65% increase in both basal insulin (P = 0.0005) and C-peptide (P =
      0.0002) concentrations in all subjects with advancing gestation. There was a
      significant (P = 0.0001) decrease in the ability of the infused insulin to
      decrease basal C-peptide concentration. C-peptide as a percentage of the basal
      was 64% before conception, 74% in early pregnancy, and 108% in late pregnancy.
      The metabolic clearance rate of insulin significantly (P = 0.0005) increased with
      advancing gestation: pregravid 442 ml.m-2.min-1, early pregnancy 514 ml.m-2. min
      1, and 526 ml.m-2.min-1 in late pregnancy. CONCLUSIONS: Pregnancy is accompanied
      by progressive alterations in insulin kinetics, which are partly responsible for
      the hyperinsulinemia of this condition. These alterations are more likely a
      homeostatic response to the increased physiological insulin resistance of
      pregnancy.

PMID- 9540031
TI  - Treatment of vulvovaginal candidiasis in patients with diabetes.

PMID- 9540032
TI  - American Diabetes Association Annual Meeting, 1997. Improvement of the quality of
      diabetes care.

PMID- 9540020
TI  - Ethnic differences in correlates of microalbuminuria in NIDDM. The role of the
      acute-phase response.
AB  - OBJECTIVE: To investigate whether microalbuminuria is associated with markers of
      the acute-phase response in NIDDM and whether there are ethnic differences in
      this association among the three main racial groups in Malaysia. RESEARCH DESIGN
      AND METHODS: NIDDM patients of Chinese, Indian, and Malay origin attending a
      diabetic clinic in Kuala Lumpur, Malaysia, were matched for age, sex, diabetes
      duration, and glycemic control (n = 34 in each group). Urinary albumin-to
      creatinine ratio was measured in an early morning urine sample. Biochemical
      measurements included markers of the acute-phase response: serum sialic acid,
      triglyceride, and (lowered) HDL cholesterol. RESULTS: The frequency of
      microalbuminuria did not differ among the Chinese, Indian, and Malay patients
      (44, 41, and 47%, respectively). In Chinese patients, those with microalbuminuria
      had evidence of an augmented acute-phase response, with higher serum sialic acid
      and triglyceride and lower HDL cholesterol levels; and urinary albumin-to
      creatinine ratio was correlated with serum sialic acid and triglyceride. The
      acute-phase response markers were not different in Indians, with microalbuminuria
      being high in even the normoalbuminuric Indians; only the mean arterial blood
      pressure was correlated with urinary albumin-to-creatinine ratio in the Indians.
      Malay NIDDM subjects had an association of microalbuminuria with acute-phase
      markers, but this was weaker than in the Chinese subjects. CONCLUSIONS:
      Microalbuminuria is associated with an acute-phase response in Chinese NIDDM
      patients in Malaysia, as previously found in Caucasian NIDDM subjects. Elevated
      urinary albumin excretion has different correlates in other racial groups, such
      as those originating from the Indian subcontinent. The acute-phase response may
      have an etiological role in microalbuminuria.

PMID- 9540033
TI  - The diagnosis of preexisting diabetes associated with acute myocardial
      infarction.

PMID- 9540026
TI  - Treatment of a unique anemia in patients with IDDM with epoetin alfa.
AB  - OBJECTIVE: To identify and treat a unique form of anemia in patients with long
      term IDDM. RESEARCH DESIGN AND METHODS: Patients with IDDM, unexplained
      symptomatic anemia, and serum creatinine levels of < 177 mumol/l (2.0 mg/dl) were
      treated with epoetin alfa (Procrit, Ortho Biotech, Raritan, NJ), 50 U/kg three
      times weekly, subcutaneously, to reach a target hematocrit of 38-40%. Baseline
      serum erythropoietin titers were measured before drug therapy. RESULTS: Six
      patients were treated with epoetin alfa. Median age of the group was 74 years,
      with IDDM being diagnosed for a median of > 20 years. All patients had symptoms
      of anemia with a median hematocrit of 28.9% (range 27-31). Compared with iron
      deficiency control patients, the group had a limited erythropoietin (EPO)
      response to the degree of anemia. All patients showed increases in hematocrit,
      median peak of 40.9%, with median time-to-peak response of 12 weeks. Baseline
      symptoms of anemia resolved in all patients. No adverse effects were noted during
      the treatment period. CONCLUSIONS: There is a unique form of anemia in patients
      with long-term IDDM and clinically normal renal function who respond to low-dose
      epoetin alfa therapy. The rapid response to therapy and depressed baseline
      erythropoietin titers suggest the anemia is due to a lack of endogenous EPO
      release.

PMID- 9540027
TI  - Induction of beta-cell rest in type 1 diabetes. Studies on the effects of
      octreotide and diazoxide.
AB  - OBJECTIVE: To evaluate the inhibitory effects of octreotide and diazoxide on
      insulin secretion in patients with type 1 diabetes and measurable levels of
      circulating C-peptide. RESEARCH DESIGN AND METHODS: Diazoxide was given to six
      patients during a 7-day period (100 mg three times daily), followed by a 3-week
      washout. Subsequently, octreotide (50 micrograms, three times daily) was
      administered subcutaneously for 7 days. Pre- and post- prandial blood glucose and
      serum C-peptide concentrations were measured before medication (control) and on
      day 7 of each medication period. Glucagon-stimulated C-peptide was determined in
      the morning before medication and on the day after each treatment period.
      RESULTS: Diazoxide inhibited glucagon-stimulated C-peptide secretion (mean
      increment 0.08 nmol/l vs. 0.18 nmol/l, P < 0.05), whereas octreotide had no such
      effect. Both reduced the pre- and postprandial serum C-peptide concentrations (P
      < 0.05), octreotide being the more potent in this respect. A reduction in basal
      and meal-related blood glucose was observed during octreotide treatment, whereas
      the glucose concentrations tended to be higher during treatment with diazoxide
      than during the 24-h control period. CONCLUSIONS: The study indicates that the
      two drugs reduce insulin output by different mechanisms. Diazoxide inhibits
      hormonal release directly on the beta-cells, whereas octreotide exerts its effect
      indirectly, presumably by multiple actions on insulin sensitivity and insulin
      releasing hormones. The results suggest that each drug is capable of inducing
      beta-cell rest in type 1 diabetes.

PMID- 9540034
TI  - How well do patients with type 1 diabetes measure their blood glucose in daily
      life.

PMID- 9540035
TI  - A word of caution on the use of lispro.

PMID- 9540028
TI  - Angiotensinogen T235 and ACE insertion/deletion polymorphisms associated with
      albuminuria in Chinese type 2 diabetic patients.
AB  - OBJECTIVE: Genetic polymorphisms of the renin-angiotensin system (RAS) have been
      implicated in the pathogenesis of diabetic proteinuria. Ethnic differences in the
      frequencies of these genotypes have also been reported. To date, most of these
      studies have been performed in white and Japanese populations. In this study, we
      examined the associations between albuminuria and RAS genetic polymorphisms in
      Chinese patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: In a case
      control study, the ACE insertion/deletion (I/D) gene, the angiotensinogen (AGT)
      gene (M235T), and the angiotensin II (AII) type 1 receptor gene (AT1 A1166C) were
      examined in 110 Chinese type 2 diabetic patients. Increased urinary albumin
      excretion (UAE) was defined as > or = 30 mg/day on at least two occasions during
      a 6-week study period. RESULTS: Compared with whites, there were high frequencies
      of the AGT TT genotype in Chinese control subjects (120/183 = 70%) and type 2
      diabetic patients (74/110 = 67%). The frequencies of the MM genotype were 5 and
      3%, respectively, and those of the ACE DD genotype were 13 and 10%, respectively.
      Although 9% of subjects carried the C allele, the AT1 CC genotype was not found
      in either group. Chinese type 2 diabetic patients with increased albuminuria (n =
      56) had higher systolic blood pressure (160 +/- 26 mmHg vs 145 +/- 27 mmHg, P <
      0.001) than the normoalbuminuric patients (n = 54). Both the AGT TT genotype
      (78.6% [44/56] vs. 55.6% [30/54], odds ratio [OR]: 3.0 [1.3-6.8]) and the T
      allele (88% [99/112] vs. 77% [83/108], OR: 2.5 [1.3-5.4]) were associated with an
      increased risk of albuminuria. Patients with the AGT TT genotype (n = 74) had
      higher 24-h UAE than those with the MT or MM genotypes (n = 36) (median: 37.8
      mg/day vs. 17.8 mg/day, P < 0.01). This association remained significant in
      patients with normotension (56 mg/day [n = 19] for patients with the TT genotype
      vs. 22 mg/day [n = 14] for those with the MT/MM genotype, P = 0.03). The D allele
      carriers (DD or DI, n = 61) had higher serum ACE activities (75.5 +/- 29 U/l vs.
      60.5 +/- 36.3 U/l, P < 0.01) than the noncarriers (II genotype). The median 24-h
      UAE also tended to be higher in the D allele carriers (38.9 mg/day vs. 21.4
      mg/day, P = 0.07). The lowest UAE was observed in patients with the MM/MT/II
      genotype (16.3 mg/day [n = 18]) and the highest, in patients with the TT/DD/DI
      genotype (52.3 mg/day [n = 43]). No association was found between the TT genotype
      or D allele and hypertension. CONCLUSIONS: The high frequencies of the TT
      genotype and T allele in Chinese populations may contribute to the high
      prevalence of albuminuria in patients with type 2 diabetes. The possibility of
      synergism between the AGT TT genotype and the ACE D allele should also be
      explored.

PMID- 9540025
TI  - Chronic treatment of African-American type 2 diabetic patients with alpha
      glucosidase inhibition.
AB  - OBJECTIVE: To evaluate the long-term efficacy, safety, and tolerability of the
      alpha-glucosidase inhibitor miglitol in the treatment of African-American
      patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 345
      African-American type 2 diabetic patients (mean age 55.6 years, BMI 31.9 kg/m2,
      duration of diabetes 4.9 years, baseline HbA1C 8.7%) treated with either diet
      alone or sulfonylurea were randomized to 1 year of double-blind treatment with
      either placebo (n = 117) or miglitol (n = 228) at doses of 50 or 100 mg t.i.d.,
      titrated based on tolerability. The primary efficacy criterion was change from
      baseline in HbA1C at the 6-month visit. Secondarily efficacy parameters included
      changes from baseline in plasma glucose and serum insulin (both fasting and 120
      min after a standardized test meal), fasting lipids, and urinary albumin-to
      creatinine ratio. Safety and tolerability evaluations were primarily based on
      reporting of adverse events and symptoms and on periodic laboratory analyses.
      RESULTS: Miglitol treatment was associated with a mean placebo-subtracted
      reduction in HbA1C from baseline of 1.19% at 6 months. Fasting and 120-min
      postprandial plasma glucose levels were reduced in parallel to HbA1C, in
      association with miglitol treatment. Significant reductions versus placebo in 120
      min postprandial insulin levels, in LDL cholesterol, and in fasting
      triglycerides, were also seen in the miglitol group at individual study time
      points. Softer, more frequent stools and flatulence were significantly more
      common in the miglitol group. Urinary tract infections, hematuria, and herpes
      simplex infections were significantly more common in the placebo group.
      CONCLUSIONS: Miglitol treatment appears to be at least as efficacious in the
      African-American type 2 population as in the U.S. type 2 population at large,
      with comparable tolerability. alpha-Glucosidase treatment may be an important
      therapeutic option in these patients in view of their greater risk for
      microvascular complications and the accumulating body of evidence that better
      glucose control reduces the risk of these complications.

PMID- 9540024
TI  - Long-term titrated-dose alpha-glucosidase inhibition in non-insulin-requiring
      Hispanic NIDDM patients.
AB  - OBJECTIVE: To assess the long-term safety and effectiveness of a titrated dose of
      the alpha-glucosidase inhibitor miglitol (BAY m 1099) in Hispanic NIDDM patients.
      RESEARCH DESIGN AND METHODS: A 1-year double-blind randomized placebo-controlled
      study in which diet-treated or diet plus sulfonylurea-treated Hispanic NIDDM
      patients received either placebo (n = 131) or miglitol in doses of 50, 100, 150,
      200 mg t.i.d. (n = 254), up-titrated and down-titrated based on tolerability.
      Efficacy parameters included changes from baseline in HbA1c, fasting and 2-h
      postprandial plasma glucose and serum insulin, fasting serum lipids, and urinary
      albumin-to-creatinine ratio (ACR). Safety assessments consisted primarily of
      tabulation of adverse events and intercurrent illnesses, and of periodic
      laboratory determinations. RESULTS: Reductions from baseline in HbA1c levels at
      the 6-month (primary efficacy) endpoint were significantly greater by 0.83% in
      the miglitol group than in the placebo group. HbA1c reductions in the miglitol
      treatment group significantly exceeded those in the placebo group by 0.63, 0.73,
      and 0.92% at 3, 9, and 12 months of treatment, respectively. Reductions in 120
      min postprandial glucose and insulin levels were significantly greater in the
      miglitol group than in the placebo group at all postbaseline visits. There was
      little difference between treatments for changes in fasting insulin or lipid
      levels. Miglitol-associated reductions versus placebo in fasting plasma glucose
      (P = 0.0587 at 6 months) and in ACR (P = 0.0541 at 1-year) were nearly
      statistically significant. These efficacy results were not notably different
      between the 6-month endpoint, at which time the mean miglitol dose was 100 mg
      t.i.d., and the 1-year visit, when the mean miglitol dose was 149 mg t.i.d.
      Notable adverse events seen significantly more often in the miglitol group than
      in the placebo group were flatulence and diarrhea (or soft stools). The incidence
      of these gastrointestinal adverse events appeared to be dose dependent.
      CONCLUSIONS: Miglitol treatment of non-insulin-requiring Hispanic NIDDM patients
      at doses from 50 to 200 mg t.i.d. produced statistically and clinically
      significant reductions of HbA1c, primarily associated with reduction of glucose
      and insulin levels in the postprandial period, which were sustained over a year
      of treatment. Adverse events related to the drug's mechanism of action were
      common, but generally well tolerated. Doses above 100 mg t.i.d. were not
      associated with notably enhanced efficacy in most patients.

PMID- 9540039
TI  - Cost-effectiveness of treatment of type 2 diabetes.

PMID- 9540041
TI  - Revised etiologic classification of diabetes.

PMID- 9540036
TI  - Medicine and the media.

PMID- 9540037
TI  - Genetic variation in promoter (4G/5G) of plasminogen activator inhibitor 1 gene
      in type 2 diabetes. Absence of relationship with microangiopathy.

PMID- 9540038
TI  - Uremia and HbA1c measured by high-performance liquid chromatography.

PMID- 9540044
TI  - New classification of diabetes.

PMID- 9540043
TI  - Screening for diabetes in obese patients using the new diagnostic criteria.

PMID- 9540040
TI  - Different effects of acarbose and voglibose on serum 1,5-anhydroglucitol
      concentrations.

PMID- 9540045
TI  - Risk of severe hypoglycemia in diabetes patients taking ACE inhibitors.

PMID- 9540046
TI  - ACE inhibitors and risk of hypoglycemia in people with diabetes.

PMID- 9540042
TI  - Response to the Expert Committee on the Diagnosis and Classification of Diabetes
      Mellitus.

PMID- 9540055
TI  - A possible role for somatostatin receptor scintigraphy in the diagnosis and
      follow-up of children with medulloblastoma.
AB  - The surgical resection of medulloblastoma (MB), the most frequent malignant brain
      tumor in children, often remains subtotal. To estimate the response to further
      treatment the residual tumor is monitored by CT or MRI. The interpretation of
      both imaging techniques is complicated by disturbances resulting from surgery and
      radiation. Our study searched for alternative imaging techniques and asked the
      following questions. 1) Do MB express somatostatin receptors (SSTR), 2) is SSTR
      scintigraphy a sensitive imaging technique for the follow-up and the detection of
      vital tumor tissue in children with MB, and 3) do the results of SSTR
      scintigraphy correlate with the in vitro analysis of MB tissue by SSTR
      autoradiography. We analyzed the SSTR status in 20 children with MB, aged 1 to 15
      years. Sixteen SSTR scintigraphies using Indium-111-DTPA-D-Phel-pentetreotide
      were performed in 14 children. MB tissue of 14 children was analyzed by SSTR
      autoradiography using Iodine-125-Tyr3-octreotide. In 8 cases SSTR were measured
      by both methods in vivo and in vitro. In comparison with conventional imaging,
      results of SSTR scintigraphy were true positive in 7 of 7 patients, true negative
      in 9 of 9 patients, including one patient with false positive findings in MRI,
      false negative in only one patient with small spinal metastases (diameter < 3 mm)
      and false positive in none of the analyzed patients. In all cases with residual
      tumor (n = 3) and suspected relapse (n = 4) the diagnosis could be confirmed (n =
      4) or excluded (n = 3), consistent with the results of MRI and tumor histology.
      All MB tissues analyzed by SSTR autoradiography (n = 14) showed an extremely high
      density of SSTR ranging from 4047 to 15526 dpm/mg MB tissue. MB (n = 8) which
      were analyzed by SSTR scintigraphy and autoradiography demonstrated consistent
      results in evaluation by both methods. In cases where the integrity of the blood
      brain barrier was tested by Tc-99m-DTPA scintigraphy (n = 10), the SSTR-to-brain
      scintigraphy index confirmed the tumor specificity of radionuclide uptake. We
      conclude that 1) MB tissue expresses a particularly high density of SSTR, 2) the
      high density of SSTR in autoradiography correlates with a sensitive imaging of
      these tumors by SSTR scintigraphy, 3) SSTR scintigraphy might be a valuable
      imaging method for detection of vital MB tissue in patients with residual tumor
      or relapse.

PMID- 9540049
TI  - Wave propagation mediated by GABAB synapse and rebound excitation in an
      inhibitory network: a reduced model approach.
AB  - A reduction method is used to analyze a spatially structured network model of
      inhibitory neurons. This network model displays wave propagation of
      postinhibitory rebound activity, which depends on GABAB synaptic interactions
      among the neurons. The reduced model allows explicit solutions for the wavefronts
      and their velocity as a function of various parameters, such as the synaptic
      coupling strength. These predictions are shown to agree well with the numerical
      simulations of the conductance-based biophysical model.

PMID- 9540048
TI  - Entrainment, instability, quasi-periodicity, and chaos in a compound neural
      oscillator.
AB  - We studied the dynamical behavior of a class of compound central pattern
      generator (CPG) models consisting of a simple neural network oscillator driven by
      both constant and periodic inputs of varying amplitudes, frequencies, and phases.
      We focused on a specific oscillator composed of two mutually inhibiting types of
      neuron (inspiratory and expiratory neurons) that may be considered as a minimal
      model of the mammalian respiratory rhythm generator. The simulation results
      demonstrated how a simple CPG model--with a minimum number of neurons and mild
      nonlinearities--may reproduce a host of complex dynamical behaviors under various
      periodic inputs. In particular, the network oscillated spontaneously only when
      both neurons received adequate and proportionate constant excitations. In the
      presence of a periodic source, the spontaneous rhythm was overridden by an
      entrained oscillation of varying forms depending on the nature of the source.
      Stable entrained oscillations were inducible by two types of inputs: (1) anti
      phase periodic inputs with alternating agonist-antagonist drives to both neurons
      and (2) a single periodic drive to only one of the neurons. In-phase inputs,
      which exert periodic drives of similar magnitude and phase relationships to both
      neurons, resulted in varying disruptions of the entrained oscillations including
      magnitude attenuation, harmonic and phase distortions, and quasi-periodic
      interference. In the absence of significant phasic feedback, chaotic motion
      developed only when the CPG was driven by multiple periodic inputs. Apneic
      episodes with repetitive alternation of active (intrinsic oscillation) and
      inactive (cessation of oscillation) states developed when the network was driven
      by a moderate periodic input of low frequency. Similar results were demonstrated
      in other, more complex oscillator models (that is, half-center oscillator and
      three-phase respiratory network model). These theoretical results may have
      important implications in elucidating the mechanisms of rhythmogenesis in the
      mature and developing respiratory CPG as well as other compound CPGs in mammalian
      and invertebrate nervous systems.

PMID- 9540051
TI  - Analytical and simulation results for stochastic Fitzhugh-Nagumo neurons and
      neural networks.
AB  - An analytical approach is presented for determining the response of a neuron or
      of the activity in a network of connected neurons, represented by systems of
      nonlinear ordinary stochastic differential equations--the Fitzhugh-Nagumo system
      with Gaussian white noise current. For a single neuron, five equations hold for
      the first- and second-order central moments of the voltage and recovery
      variables. From this system we obtain, under certain assumptions, five
      differential equations for the means, variances, and covariance of the two
      components. One may use these quantities to estimate the probability that a
      neuron is emitting an action potential at any given time. The differential
      equations are solved by numerical methods. We also perform simulations on the
      stochastic Fitzugh-Nagumo system and compare the results with those obtained from
      the differential equations for both sustained and intermittent deterministic
      current inputs with superimposed noise. For intermittent currents, which mimic
      synaptic input, the agreement between the analytical and simulation results for
      the moments is excellent. For sustained input, the analytical approximations
      perform well for small noise as there is excellent agreement for the moments. In
      addition, the probability that a neuron is spiking as obtained from the empirical
      distribution of the potential in the simulations gives a result almost identical
      to that obtained using the analytical approach. However, when there is sustained
      large-amplitude noise, the analytical method is only accurate for short time
      intervals. Using the simulation method, we study the distribution of the
      interspike interval directly from simulated sample paths. We confirm that noise
      extends the range of input currents over which (nonperiodic) spike trains may
      exist and investigate the dependence of such firing on the magnitude of the mean
      input current and the noise amplitude. For networks we find the differential
      equations for the means, variances, and covariances of the voltage and recovery
      variables and show how solving them leads to an expression for the probability
      that a given neuron, or given set of neurons, is firing at time t. Using such
      expressions one may implement dynamical rules for changing synaptic strengths
      directly without sampling. The present analytical method applies equally well to
      temporally nonhomogeneous input currents and is expected to be useful for
      computational studies of information processing in various nervous system
      centers.

PMID- 9540052
TI  - Four-dimensional analysis of human brain tumor spheroid invasion into fetal rat
      brain aggregates using confocal scanning laser microscopy.
AB  - The advent of confocal microscopy and fluorescence probes has made possible the
      routine visualization of the complex three-dimensional structures of thick fixed
      or live specimens. Four-dimensional (4-D) imaging of biological specimens (three
      dimensional image reconstruction of the same living sample at different time
      points), remains a seldom-used application of confocal microscopy. In the present
      study we used 4-D imaging techniques to quantitate the invasion of human brain
      tumor spheroids into fetal rat brain aggregates (FRBAs), using the vital
      fluorescence membrane dyes, 3, 3'-Dioctadecyloxacarbocyanine perchlorate (DiO)
      and 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) as
      visualization probes. We found invasion patterns similar to the in vivo behavior
      of these tumors in the brain. Glioblastoma spheroids showed diffuse and
      circumscribed infiltration accompanied by cystic degeneration or necrosis of
      FRBAs. Spheroids from cerebral metastasis, however, showed a sharp delimitation
      of the invasive margin, and did not penetrate the FRBA beyond a depth of 55
      microns. Measured rates of glioblastoma invasion varied with the tumor specimens
      examined. The slopes of the mid-portions of plots of % infiltration vs. time
      (hours) for four glioblastoma cell lines were 1.7 +/- 0.21 (SD), 0.67 +/- 0.11,
      1.4 +/- 0.22 and 1.3 +/- 0.18. We conclude that confocal microscopy with vital
      fluorescence probes is a practical method that allows for close monitoring and
      quantitation of the process of invasion in live tissue preparations, and may be
      used for assessing the in vitro effects of various tumor treatments.

PMID- 9540047
TI  - A mathematical model of the cerebellar-olivary system I: self-regulating
      equilibrium of climbing fiber activity.
AB  - We use a mathematical model to investigate how climbing fiber-dependent
      plasticity at granule cell to Purkinje cell (gr-->Pkj) synapses in the cerebellar
      cortex is influenced by the synaptic organization of the cerebellar-olivary
      system. Based on empirical studies, gr-->Pkj synapses are assumed to decrease in
      strength when active during a climbing fiber input (LTD) and increase in strength
      when active without a climbing fiber input (LTP). Results suggest that the
      inhibition of climbing fibers by cerebellar output combines with LTD/P to self
      regulate spontaneous climbing fiber activity to an equilibrium level at which LTP
      and LTD balance and the expected net change in gr-->Pkj synaptic weights is zero.
      The synaptic weight vector is asymptotically confined to an equilibrium
      hyperplane defining the set of all possible combinations of synaptic weights
      consistent with climbing fiber equilibrium. Results also suggest restrictions on
      LTP/D at gr-->Pkj synapses required to produce synaptic weights that do not drift
      spontaneously.

PMID- 9540053
TI  - Expression of annexin II in glioma cell lines and in brain tumor biopsies.
AB  - Annexin II is a calcium and phospholipid binding protein and a substrate for
      protein-tyrosine kinases. Increased levels of annexin II are observed in various
      cancer cells and tissues, and the molecule has been proposed as a marker of
      malignancy in vivo. Annexin II was expressed in four glioma cell lines (D-54MG, D
      37MG, U251MG and GaMG), as determined by Western blot analyses,
      immunofluorescence staining and flow cytometric measurements. In addition,
      annexin II expression was also found in cryostat sections obtained from 15
      consecutive brain tumor biopsies: Ten were histologically classified as
      glioblastomas, one as an astrocytoma, two as meningiomas and two as brain
      metastases. Cultured spheroids from the glioma cell lines and from three of the
      glioblastoma biopsies showed lower levels of annexin II, than found in the
      monolayers of the cell lines and in the freshly cut biopsies. The annexin II
      expression of the cell lines were not found to be related to their proliferative,
      migratory or invasive properties. These findings indicate that although annexin
      II may serve as a marker of malignancy in vivo, its expression can be reduced in
      vitro, and appear unrelated to malignant features of glioma cell lines.

PMID- 9540054
TI  - Assessment of the peripheral benzodiazepine receptors in human gliomas by two
      methods.
AB  - This study was designed to evaluate the density of peripheral benzodiazepine
      receptor (PBR) sites as a function of tumor malignancy in human gliomas, and to
      compare the results obtained with autoradiographic and liquid scintillation
      measurements performed on the same tissue specimens. In vitro binding of [3H]PK
      11195[1-(2-chlorophenyl)-N-methyl-(1-methylpropyl)-3-isoguinol ine carboxamide]
      to human gliomas in radioligand binding studies revealed a significantly higher
      level (about 3 fold) of PBR binding sites in both low grade and high grade
      gliomas as compared to normal cortex. The Bmax (mean +/- SD) of high and low
      grade gliomas, when entire tissue sections were measured by autoradiography, was
      5.5 +/- 0.3 pmol/mg-tissue (n = 5) and 1.8 +/- 0.9 pmol/mg-tissue (n = 6),
      respectively, although it was evident that there was area of hot spots in the
      high grade tumors. This difference was significant (p < 0.05; two-tailed t-test).
      Similarly, the KD values (dissociation constant; nM) between the high (KD = 20.4
      +/- 1.3 nM) and low (KD = 14.3 +/- 2.1 nM) grade gliomas were significantly
      different. A significant difference in binding site density (Bmax) between the
      two types of gliomas was also obtained in liquid scintillation measurements. The
      hot spot areas which showed the most intense binding of [3H]PK-11195 had KD of
      24.5 +/- 1.0 nM and Bmax of 6.2 +/- 0.42 pmol/mg-tissue, values significantly
      higher (p < 0.05, two-tailed t-test) than those obtained when the entire tissue
      section was measured. The data on the Bmax/KD ratios presented here suggest that
      it might be possible to differentiate high from low grade gliomas in human by in
      vivo imaging with 11C-labelled PK-11195.

PMID- 9540050
TI  - A mathematical model of the cerebellar-olivary system II: motor adaptation
      through systematic disruption of climbing fiber equilibrium.
AB  - The implications for motor learning of the model developed in the previous
      article are analyzed using idealized Pavlovian eyelid conditioning trials, a
      simple example of cerebellar motor learning. Results suggest that changes in gr-
      >Pkj synapses produced by a training trial disrupt equilibrium and lead to
      subsequent changes in the opposite direction that restore equilibrium. We show
      that these opposing phases would make the net plasticity at each gr-->Pkj synapse
      proportional to the change in its activity during the training trial, as
      influenced by a factor that precludes plasticity when changes in activity are
      inconsistent. This yields an expression for the component of granule cell
      activity that supports learning, the across-trials consistency vector, the square
      of which determines the expected rate of learning. These results suggest that the
      equilibrium maintained by the cerebellar-olivary system must be disrupted in a
      specific and systematic manner to promote cerebellar-mediated motor learning.

PMID- 9540057
TI  - The effect of the anti-angiogenic agent TNP-470 on tumor growth and vascularity
      in low passaged xenografts of human gliomas in nude mice.
AB  - The effect of the anti-angiogenic agent TNP-470 on tumor growth, vascular area,
      vascular density and tumor perfusion of two different subcutaneously implanted
      human glioma xenografts (E98 and E106) in nude mice was evaluated. Vascular
      parameters were investigated with an image analysis system. For both tumor lines
      a small but significant tumor growth suppression was observed. However, no
      differences in vascular parameters between TNP-470 treated tumors and controls
      could be found after 6 weeks of treatment. It is concluded that although TNP-470
      is a promising anti-angiogenic agent in many tumor types, at least 2 glioma lines
      seem to be partly resistant to its anti-angiogenic effects. Further evaluation of
      the effects of combination of TNP-470 and cytostatic agents or radiotherapy in
      human glioma xenografts are required to determine the place of anti-angiogenic
      therapy in general and treatment with the anti-angiogenic agent TNP-470 more
      specifically in the treatment of human gliomas.

PMID- 9540056
TI  - Expression of p53, MDM2 protein and Ki-67 antigen in recurrent meningiomas.
AB  - Association of p53 gene abnormalities with tumor progression and prognosis of
      many neoplasms has been demonstrated, but little is known about the clinical
      significance of p53 abnormalities in meningiomas. The significance of p53 protein
      expression in recurrent meningiomas and its relationships with MDM2 protein and
      proliferation activity were investigated by analyzing 39 meningiomas
      immunohistochemically. p53 protein was expressed in 11 (35%) of 31 non-recurrent
      and 7 (88%) of 8 recurrent meningiomas. A high frequency of p53 expression was
      observed in recurrent meningiomas, which tended to have a high p53 positive index
      (p53 PI), indicating that p53 immunoreactivity may be a marker for predicting
      tumor recurrence. Four recurrent meningiomas with high p53 PIs were analyzed by
      the polymerase chain reaction-single strand conformation polymorphism method to
      detect p53 gene mutations, but none were found in exons 4-8 of this gene. Fifteen
      (71%) of 21 MDM2-positive and 3 (17%) of 18 MDM2-negative tumors expressed p53
      protein, showing that MDM2 expression was more common in meningiomas with p53
      expression. p53 immunoreactivity in the absence of mutation may indicate
      stabilization of the wild type through interaction with the MDM2 protein. The Ki
      67/MIB-1 proliferation index (MIB-1 PI) correlated well with recurrence. The p53
      positive tumors had a significantly higher mean MIB-1 PI than p53-negative
      tumors, suggesting that wild-type p53 inactivation by the MDM2 protein may be
      involved in controlling the proliferative activity in meningiomas. In conclusion,
      immunohistochemical examination for p53 protein as well as proliferative activity
      may help predict the malignant potential of tumor recurrence.

PMID- 9540059
TI  - Neurotoxicity of combination chemotherapy with procarbazine, CCNU and vincristine
      (PCV) for recurrent glioma.
AB  - In cerebral glioma combination chemotherapy with procabazine, CCNU and
      vincristine (PCV) is used as adjuvant therapy in cases of recurrence. Standard
      PCV is usually well tolerated, but intensive PCV (CCNU 130 mg/m2 on day 1,
      procarbazine 75 mg/m2 on day 8-21, vincristine 1.4 mg/m2 on day 8 and 29; 6
      courses every 6 weeks) is less well tolerated. We observed central neurotoxic
      side effects (focal neurological deficit, cognitive disturbances, slowing of EEG
      background activity, atrophy on cerebral MR) in combination with hematological
      and hepatic toxicity in four of 26 PCV treated patients with recurrent glioma.
      Prolonged myelo-suppression and/or ongoing (partial reversible in two patients)
      neurological deficit still influence daily life in three of four patients months
      after discontinuation of chemotherapy. Despite the fact that all four patients
      used anticonvulsants and have been treated with radiotherapy in the past, we have
      the strong impression that central neurotoxic side effects are related to
      intensive PCV therapy. We advocate to use the standard PCV regimen in patients
      with recurrent glioma, because of this potential toxicity and the lack of
      evidence that intensive PCV leads to better tumor control than standard PCV in
      cerebral glioma.

PMID- 9540061
TI  - Bihemispheric malignant glioma: one size does not fit all.
AB  - Recurrence of malignant glioma following radiotherapy most commonly occurs in
      close proximity to the original contrast enhancing CT/MRI tumor volume. For this
      reason current radiation planning favors focal radiotherapy fields designed to
      cover the preoperative tumor contrast enhancing volume +/- surrounding edema with
      a 2-4 centimetre margin. Two patients with bifrontal malignant gliomas treated
      with such radiotherapy fields experienced out of field tumor progression while on
      treatment. Posterior extension along the corpus callosum, not evident on
      pretreatment imaging, was hypothesized as the cause of the geographic miss. The
      literature documenting recurrence patterns of malignant glioma following
      radiotherapy support focal field radiotherapy fields for most patients with
      malignant glioma. Reporting bias may exist in the literature, however, due to the
      whole brain radiotherapy used in older series reporting recurrence patterns and
      exclusion of patients with bihemispheric or more locally extensive tumors in more
      modern series. Tumor location and pattern of growth at presentation may be
      important factors in predicting patterns of spread and relapse after
      radiotherapy.

PMID- 9540058
TI  - Tamoxifen and carboplatin combinational treatment of high-grade gliomas. Results
      of a clinical trial on newly diagnosed patients.
AB  - Between April, 1992 and December, 1995, forty consecutive patients with a
      cerebral malignant glioma (WHO Grade III and IV) were enrolled in a trial
      consisting in surgery and post-operative administration of radiotherapy (4500
      6000 cGy), carboplatin (CBDCA; dose of 450-600 mg/m2), and oral tamoxifen (TAM;
      at doses of 40, 80 or 120 mg/day). Two patients of the TAM group died in the
      postoperative period from a pulmonary embolism and myocardial infarction,
      respectively. The patients (all dosages combined) had a median survival time of
      13 months from the time of diagnosis. The 12-month and 24-month survival rates
      were 52% and 32%, respectively. The median relapse-free survival time was 7
      months. Patients treated with higher doses of TAM (80-120 mg/day) demonstrated a
      longer median survival rate (13 months both) and a longer 12-month survival
      result (58% and 76%, respectively). Patients who assumed TAM for a period longer
      than 3 months (group +3) have a higher median survival rate (16 months) and
      better 12-month and 24-month results (62% and 40%, respectively). Moreover, the
      median relapse-free survival time was 10 months (versus 6 months in group -3; p =
      0.0038). However, it is not possible to exclude that patients of group +3 had a
      slower growing or a stable tumor and were well enough to assume TAM for a longer
      period. The results observed in the TAM-group have been compared with those of 40
      matched controls treated with surgery, radiotherapy and CBDCA. These patients had
      a median survival time of 9 months (p = 0.04) and the 12-month and 24-month
      survival rates were 30% and 0%, respectively. The median relapse-free survival
      time was 4 months (p = 0.0014). These data suggest a potential role for
      combinational TAM-CBDCA therapy in the post-operative treatment of cerebral
      malignant gliomas; further clinical phase III trials, especially those with
      higher dosages of TAM are warranted.

PMID- 9540060
TI  - Rare combination of spinal lesions and subcutaneous meningioma in a 44 year old
      man.
AB  - A 44 year-old man with subcutaneous meningioma and rare combination of spinal
      lesions, consisting of dermal sinus and lipoma of the filum terminale. The
      literature concerning the subcutaneous meningioma is reviewed and the
      embryogenesis of these lesions is discussed.

PMID- 9540064
TI  - Contribution of topoisomerase I to conversion of single-strand into double-strand
      DNA breaks.
AB  - An in vitro system composed of nicked pBR322 DNA and purified topoisomerase I was
      employed to study the efficiency of the topoisomerase I-driven single-strand to
      double-strand DNA breaks conversion. At 1.4 x 10(5) topoisomerase I activity
      units per mg DNA about 20% single-strand nicks were converted into double-strand
      breaks during 30 min due to topoisomerase I action. Camptothecin inhibited the
      conversion. The conversion was also inhibited when the relaxing activity of the
      used topoisomerase I was increased by phosphorylation of the enzyme with casein
      kinase 2. The presented data suggest that topoisomerase I may be involved in
      production of double-stranded breaks in irradiated cells and that this process
      positively depends on the amount of topoisomerase I but not on its
      phosphorylation state.

PMID- 9540062
TI  - The integrated activities of IRF-2 (HiNF-M), CDP/cut (HiNF-D) and H4TF-2 (HiNF-P)
      regulate transcription of a cell cycle controlled human histone H4 gene:
      mechanistic differences between distinct H4 genes.
AB  - Maximal transcription of a prototypical cell cycle controlled histone H4 gene
      requires a proliferation-specific in vivo genomic protein/DNA interaction
      element, Site II. Three sequence-specific transcription factors interact with
      overlapping recognition motifs within Site II: interferon regulatory factor IRF-2
      (HiNF-M), the putative H4 subtype-specific protein H4TF-2 (HiNF-P), and HiNF-D
      which represents a complex of the homeodomain protein CDP/cut, CDC2, cyclin A and
      pRB. However, natural sequence variation in the Site II sequences of different
      human H4 genes abolishes binding of specific trans-acting factors; the functional
      consequences of these variations have not been investigated. To address the
      precise contribution of H4 promoter factors to the level of H4 gene
      transcription, we performed a systematic mutational analysis of Site II
      transcriptional motifs. These mutants were tested for ability to bind each of the
      Site II cognate proteins, and subsequently evaluated for ability to confer H4
      transcriptional activity using chimeric H4 promoter/CAT fusion constructs in
      different cell types. We also analyzed the effect of over-expressing IRF-2 on CAT
      reporter gene expression driven by mutant H4 promoters and assessed H4
      transcriptional control in cells nullizygous for IRF-1 and IRF-2. Our results
      show that the recognition sequence for IRF-2 (HiNF-M) is the dominant component
      of Site II and modulates H4 gene transcription levels by 3 fold. However, the
      overlapping recognition sequences for IRF-2 (HiNF-M), H4TF-2 (HiNF-P) and CDP/cut
      (HiNF-D) together modulate H4 gene transcription levels by at least an order of
      magnitude. Thus, maximal activation of H4 gene transcription during the cell
      cycle in vivo requires the integrated activities of multiple transcription
      factors at Site II. We postulate that the composite organization of Site II
      supports responsiveness to multiple signalling pathways modulating the activities
      of H4 gene transcription factors during the cell cycle. Variations in Site II
      sequences among different H4 genes may accommodate differential regulation of H4
      gene expression in cells and tissues with unique phenotypic properties.

PMID- 9540067
TI  - Nucleosome positioning and periodicity of satellite DNA in the liver of aging
      rats. Nucleosome positioning and periodicity of satellite DNA.
AB  - The positioning of nucleosomes has been analysed by comparing the pattern of
      cutting sites of a probing reagent on chromatin and naked DNA. For this purpose,
      high molecular weight DNA and nuclei from the liver of young (18 +/- 2 weeks) and
      old (100 +/- 5 weeks) Wistar male rats were digested with micrococcal nuclease
      (MNase) and hybridized with 32P-labelled rat satellite DNA probe. A comparison of
      the ladder generated by MNase with chromatin and nuclei indicates long range
      organization of the satellite chromatin fiber with distinct non-random
      positioning of nucleosomes. However, the positioning of nucleosomes on satellite
      DNA does not vary with age. For studying the periodicity and subunit structure of
      satellite DNA, high molecular weight DNA from the liver of young and old rats
      were digested with different restriction enzymes. Surprisingly, no noteworthy age
      related change is visible in the periodicity and subunit structural organization
      of the satellite DNA. These results suggest that the nucleosome positioning and
      the periodicity of liver satellite DNA do not vary with age.

PMID- 9540065
TI  - Advances in the Human Genome Project. A review.
AB  - While celebrating its fifth official birthday last year it seems that the Human
      Genome Project (HGP) has and will continue to yield important biochemical
      information to mankind. It is exhilarating to think about the transition from
      studying genome structure to understanding genome function. The collective
      actions of information dessimination, technology development for efficient and
      faster sequencing, high-volume sequencing and developing model organisms has led
      to its success sofar. Various genome-wide STS-based human maps were completed in
      1995, including a genetic map, a YAC map, a RH map with, and an integrated YAC-RH
      genetic map. These maps provide comprehensive frameworks for positioning
      additional loci, with the current genetic and RH maps spanning essentially 100%
      of the human genome and the YAC maps covering 95%. Few genes, however, have yet
      been localized on these framework maps. To date the Human Genome Project has
      experienced gratifying success. The technology and data produced by the genome
      project will provide a strong stimulus to broad areas of biological research and
      biotechnology. However, enormous challenges remain.

PMID- 9540063
TI  - Nuclear matrix associated DNA-binding proteins of ocular lens epithelial cells.
AB  - Association of transcription factors with the nuclear matrix represents a
      mechanism by which nuclear architecture may influence transcriptional control of
      gene expression. This investigation examines nuclear matrix associated proteins
      (NMP's) isolated from ocular lens epithelial cells by monitoring DNA binding
      activities using consensus oligonucleotides recognized by the transcription
      factors YY1, AML-1, AP-1, SP-1 and ATF. The nuclear matrix fractions tested
      included an immortilized human lens epithelial cell line containing the SV40
      large T-antigen, and two mouse lens epithelial cell lines derived from either a
      normal mouse or a cataract mouse. A rabbit epidermal epithelial cell line and
      HeLa cells were also included in this study for comparison. The data from these
      experiments reveal that ubiquitously represented and tissue restricted regulatory
      proteins are associated with nuclear matrix of lens epithelial cells. The
      functional significance of the nuclear matrix association of these transcription
      factors remains to be determined. However, our findings raise the possibility
      that the transcription factors associated with the nuclear matrix could have
      specific roles in gene regulation and eye tissue development.

PMID- 9540069
TI  - Expression of the nuclear gene encoding mitochondrial ATP synthase subunit alpha
      in early development of Drosophila and sea urchin.
AB  - Complementary DNAs encoding nuclear-coded mitochondrial ATP synthase subunit
      alpha of Drosophila melanogaster and Strongylocentrotus purpuratus were obtained
      by a combination of library screening and redundant PCR. The entire coding
      sequence of the precursor polypeptide was inferred for both species. Southern
      blots to genomic DNA indicated that the gene is almost certainly single-copy in
      both organisms. Northern blots to RNA from staged developmental series showed
      that ATP synthase subunit alpha mRNA is represented in the egg, declines in
      abundance during cleavage, and is replenished by zygotic transcription in both
      species. However, the extent and timing of these changes differ significantly in
      the two species studied. Nuclear-coded and mitochondrially encoded ATP synthase
      genes appear to be temporally co-regulated in Drosophila, but not sea urchin
      development.

PMID- 9540070
TI  - Further characterization of human RNase MRP/RNase P and related autoantibodies.
AB  - We characterized a panel of human RNase MRP/RNase P autoantibodies by
      immunoprecipitation, immunodepletion, immunoaffinity purification and
      immunoblotting. We report on the protein spectrum that is recognized by RNase
      MRP/RNase P autoantibodies. We also describe another, related patient serum that
      based on these assays does not immunoprecipitate RNase P/MRP/Th40. This
      autoantibody 'KC', however, coimmunoprecipitates the RNase MRP/RNase P associated
      RNAs from HeLa and La9 cell extracts as shown by nuclease protection experiments.

PMID- 9540071
TI  - Oct3/4-associating proteins from embryonal carcinoma and spermatogenic cells of
      mouse.
AB  - The octamer-binding protein Oct3/4 was postulated to active transcription through
      protein-protein interactions with hypothetical cellular coactivator(s). We have
      used a bacterially produced Oct3/4, as a protein-binding probe, to detect by far
      Western assay the Oct3/4-associating proteins (OTAPs) from the embryonal
      carcinoma (EC) cells F9 and pachytene spermatocytes. Both common and cell
      specific OTAPs were shown to interact directly with Oct3/4. Differentiation of
      the EC cells results in disappearance of most of OTAPs, supporting their
      coactivator nature. Several OTAPs detected in pachytene spermatocyte may
      represent germ cell-specific Oct3/4 coactivators.

PMID- 9540068
TI  - X-ray small angle scattering study of chromatin as a function of fiber length.
AB  - This work investigates the structure of native calf thymus chromatin as a
      function of fiber length and isolation procedures by using X-ray small angle
      scattering technique. Two methods of chromatin isolation have been compared in
      order to better understand the differences reported by various authors in terms
      of chromatin high order structure. In addition to these experimental results the
      effects of shearing have also been studied. In order to explain the differences
      among these chromatin preparations we built several models of chromatin fibers
      (represented as a chain of spherical subunits) assuming increasing level of
      condensation at increasing salt concentrations. For all these fiber models the
      corresponding theoretical X-ray scattering curves have been calculated and these
      results have been used to explain the influence of fiber length on the scattering
      profiles of chromatin. The comparison between experimental and theoretical curves
      confirms that the high molecular weight chromatin-DNA prepared by hypotonic
      swelling of nuclei (without enzymatic digestion) displays a partially folded
      structure even at low ionic strength, whereas the low molecular weight chromatin
      DNA prepared by a brief nuclease digestion appears very weakly folded at the same
      ionic conditions.

PMID- 9540073
TI  - Expression of the glutathione peroxidase gene lacking its 3' untranslated region.
AB  - In order to investigate the expression of human cellular glutathione peroxidase
      (GPx), we mutated the gene encoding GPx by deleting either the 5' or 3'
      untranslated region (utr), subcloned the deleted fragments into plasmid pSVL
      followed by transfection into COS-7 cells and measured the amount of GPx
      expressed. When the 5' utr of the gene was deleted, GPx was not expressed.
      However, the deletion of the 3' utr resulted in some expression of GPx. Deletion
      of the poly A region of the GPx gene resulted in the expression of GPx but the
      level was lower than that of the full-length cGPx. The complete deletion of the
      3' utr resulted in a half of the expression of the poly A deletion mutant. Thus,
      the expression of GPx increased according to the length of the 3' utr. These
      results suggest that the GPx gene carrying one SECIS on 5' utr (FEBS Lett.
      312(1992)10-14) is essential for GPx expression. SECIS on 3' utr might not play a
      key role of GPx expression. Expression of GPx by COS-7 cells was not observed
      when a plasmid harboring an antisense gene was transfected.

PMID- 9540075
TI  - Dental education--a right or a privilege?

PMID- 9540074
TI  - Comparison of tRNA conformation during different phases of reproduction.
AB  - The present study is a comparison of tRNA conformation from ovary of
      Heteropneustes fossilis in its active phase of reproduction (when it is highly
      engaged in protein synthesis i.e. previtellogenic phase) with inactive phase
      (when tRNA is mainly stored in mature ovary i.e. spawning phase). Transfer RNA of
      active phase is shown to be compact, flexible and susceptible towards nuclease.
      Compact tRNA structure is evidenced by higher hyperchromicity and presence of
      relatively less Gm modifications thereby allowing adequate hydrogen bonding
      between D loop and T loop. Higher sensitivity of tRNA towards Mg++ reflects its
      higher flexibility towards internal environment. This structure of tRNA may be
      required for active protein synthesis. On the other hand tRNA of inactive phase
      is shown to be relaxed but resistant towards nuclease which may be favoured for
      storage in mature ova of a teleost as maternal carry over.

PMID- 9540072
TI  - Localization of autoepitopes on the PCM-1 autoantigen using scleroderma sera with
      autoantibodies against the centrosome.
AB  - Characterization of epitope domains of autoantigens is important for deducing the
      cellular functions of autoantigens and may be important for understanding the
      autoimmune response. In the reported studies, epitope analysis of the centrosome
      autoantigen PCM-1 was performed. For these investigations, portion of the PCM-1
      cDNA were subcloned into the pMAL expression plasmid, fusion proteins were
      induced, and aliquots of the extracts were probed by immunoblot analysis using
      two human autoimmune anticentrosome autoantisera. Immunoblotting identified three
      individual autoepitopes of 26-40 amino acid residues, amino acids 506-545, 1434
      1465, and 1661-1686, within the PCM-1 protein. ELISA assays using non-denatured
      proteins did not identity any additional autoepitopes in the remainder of the PCM
      1 molecule. To analyze the identified autoepitopes further, synthetic peptides
      were generated that covered each of the three autoepitopes and the synthetic
      peptides then were probed using the scleroderma sera. Peptides that covered the
      antigenic regions from amino acids 506-545 and 1434-1465 failed to react with the
      anticentrosome autoantisera suggesting that overall protein conformation may be
      important for the formation of those two autoepitopes. Peptides derived from the
      sequence of the third autoepitope were recognized by autoantibodies present in
      the anticentrosome autoantisera allowing the identification of the tripeptide KDC
      as the autoepitope in this region of the PCM-1 molecule. These studies lay the
      foundation for future investigations of the autoimmune response in scleroderma
      patients that are producing anticentrosome autoantibodies and should allow an
      investigation of the cellular role of the PCM-1 protein.

PMID- 9540078
TI  - Morphologic effects of glycerol on the mental nerve.
AB  - OBJECTIVES: In recent years, injection of pure glycerol has been used
      successfully for the treatment of trigeminal neuralgia. However, the mode of
      action of this therapy remains unclear. The present experiment was undertaken to
      examine histologically the morphologic changes produced by extraneural injections
      of pure glycerol into the dog mental nerve. STUDY DESIGN: Under direct vision,
      glycerol was injected extraneurally into the mental foramen on one side of the
      lower jaw of each of nine dogs. Physiologic saline solution was the control on
      the contralateral side of each animal. Animals were killed at 1, 3, and 7 days
      after the application of glycerol, and the mental nerve specimens were examined
      by light microscopy. RESULTS: Results showed that extraneural application of pure
      glycerol in the vicinity of the dog mental nerve is not associated with
      structural changes. No signs of nerve degeneration or other morphologic changes
      were observed for any of the experimental and control specimens in any of the
      time intervals studied. CONCLUSIONS: It can be concluded that despite the
      encouraging clinical results related to extraneural application of pure glycerol
      for treatment of trigeminal neuralgia, glycerol produces its effect without
      inducing any morphologic or destructive changes in the peripheral nerve. A
      probable explanation of the temporary clinical effectiveness of glycerol in
      relieving trigeminal neuralgia is discussed.

PMID- 9540080
TI  - Long-term outcomes of nonsurgical treatment in nonreducing anteriorly displaced
      disk of the temporomandibular joint.
AB  - OBJECTIVES: The aim of this study was to evaluate long-term outcomes of
      nonsurgical treatment in patients with persistent anterior disk displacement
      without reduction of the temporomandibular joint. STUDY DESIGN: Thirty-five
      patients were treated with occlusal splints, and 12 patients underwent additional
      occlusal treatments after splint treatment. These patients were evaluated
      clinically and radiographically. At least 2 years after the treatment, the 34
      patients' symptoms were assessed with the use of a questionnaire. RESULTS: The
      mean maximal interincisal distance (MID) was 27.6 mm before treatment and 44.4 mm
      at the end of treatment (p < 0.001). Before the treatment, all 35 patients had
      complained of pain, and mild pain persisted in 9 patients at the end of
      treatment. Flattening of the condylar head and of the articular eminence
      increased in prevalence from 12.1% and 9.1%, respectively, before treatment to
      54.5% and 51.5%, respectively, at the time of follow-up observation. At the time
      of the survey, the mean self-reported MID was 46.8 mm (p < 0.01). CONCLUSIONS:
      After the nonsurgical treatment, the clinical signs and symptoms improved
      significantly, although the prevalence of osteoarthrotic findings increased.

PMID- 9540081
TI  - Mucosal blood flow during various intravenous and inhalational anesthetics in the
      rabbit.
AB  - OBJECTIVE: The goal of this study was to compare the effects of nitrous oxide
      (N2O), isoflurane (ISO), fentanyl (FENT), and propofol (PROP) on the tongue
      mucosal blood flow (TMBF) in rabbits. STUDY DESIGN: TMBF was measured with a
      laser Doppler flow meter before and after the administration of 50% N2O (n = 7),
      1.0 and 1.5 minimum alveolar concentration ISO (n = 6), 10, 20, and 40
      micrograms/kg FENT (n = 8) or 100, 200 and 400 micrograms/kg/min PROP (n = 7).
      Hemodynamic variables including heart rate, systolic blood pressure (SBP), mean
      arterial pressure (MAP) and aortic blood flow (AoF) were continuously monitored.
      Total peripheral resistance (TPR) was calculated as MAP divided by AoF. RESULTS:
      An increase in TMBF along with reductions in SBP, MAP and TPR were observed in
      ISO group. In FENT group, TMBF was decreased, whereas other hemodynamic variables
      showed no change. TMBF in groups N2O and PROP did not change. CONCLUSION: These
      results indicate that TMBF depends on the anesthetic used.

PMID- 9540077
TI  - An association between imaging and acute posttraumatic ear bleeding with trismus.
AB  - OBJECTIVES: Computed tomography findings for each of 94 patients with unilateral
      ear bleeding and trismus correlated with either comminuted temporal bone fracture
      (26 cases) or bilateral temporomandibular joint fracture (68 cases). STUDY
      DESIGN: Ninety-four patients with post-traumatic unilateral ear bleeding and 10
      asymptomatic adults underwent coronal computed tomography examinations of their
      temporomandibular joints. Of these, 26 patients with intact temporomandibular
      joints underwent axial computed tomography of the temporal bones. For 23 of the
      94 symptomatic patients, computed tomography was the final imaging procedure; for
      the other 71 symptomatic patients, it was the first imaging procedure.
      Quantifications of the radiation dose and the per-patient cost of imaging were
      performed. Measurement of the maximal mandibular movements in vertical and
      horizontal directions was performed clinically in the 10 asymptomatic adult
      control subjects and in the 94 patients with trismus and ear bleeding. RESULTS:
      Ten control subjects had maximal opening values of 40 mm or more, and horizontal
      movement exceeded 24 mm. In 68 symptomatic patients, coronal computed tomography
      demonstrated bilateral fracture: there was bilateral high condylar fracture in 35
      patients, and there was ipsilateral to the bleeding high condylar fracture with
      contralateral subcondylar fracture dislocation in 33 patients. Axial computed
      tomography scans in 26 symptomatic patients with intact temporomandibular joints
      demonstrated comminuted petrous bone fracture ipsilateral to the ear bleeding.
      CONCLUSIONS: Patients with post-traumatic ear bleeding associated with trismus
      should first be evaluated by computed tomography. Any other initial procedure
      doubles the radiation dose as well as the cost of the imaging.

PMID- 9540076
TI  - Tuberculosis of the temporomandibular joint.

PMID- 9540066
TI  - Tissue specific and vitamin D responsive gene expression in bone.
AB  - Studies of gene expression in bone have adopted a number of molecular approaches
      that seek to determine those cis and trans-acting factors responsible for the
      development and physiological regulation of this unique tissue. The majority of
      studies have been performed in vitro, focussing on the expression of genes such
      as osteocalcin, bone sialoprotein and type I collagen which demonstrate
      restricted or altered expression patterns in osteoblasts. These studies have
      demonstrated a large number of cis and trans acting factors that modulate the
      tissue specific and vitamin D responsive expression of these genes. These include
      the response elements and regions mediating basal and vitamin D dependent
      transcription of these genes as well as some of the transcription factors that
      bind to these regions and the nucleosomal organisation of these genes within a
      nuclear framework. In vivo studies, including the introduction of transgenes into
      transgenic mice, extend these in vitro observations within a physiological
      context. However, in part due to limitations in each approach, these in vitro and
      in vivo studies are yet to accurately define all the necessary cis and trans
      acting factors required for tissue specific and vitamin D responsive gene
      expression. Advances have been made in identifying many cis-acting regions within
      the flanking regions of these genes that are responsible for their restricted
      expression patterns, but a vector incorporating all the necessary cis-acting
      regions capable of directing gene expression independent of integration site has
      not yet been described. Similarly, trans-acting factors that determine the
      developmental destiny of osteoblast progenitors and the restricted expression of
      these genes remain elusive and, despite advances in the understanding of protein
      DNA interactions at vitamin D response elements contained within these genes,
      further intermediary factors that interact with the transcriptional machinery to
      modulate vitamin D responsiveness need to be identified.

PMID- 9540079
TI  - The effect of age and gender on the onset of symptomatic temporomandibular joint
      disk displacement.
AB  - OBJECTIVE: The aim of this study was to test the hypotheses that incidence of
      symptomatic temporomandibular joint disk displacement is evenly distributed over
      all ages and between genders and that there is no gender difference in pain
      perception. STUDY DESIGN: The study population consisted of 248 consecutive
      patients with radiographically verified symptomatic temporomandibular joint disk
      displacement. The time of onset of the condition relative to age and gender was
      determined, as was pain level. RESULTS: There was a statistically significant
      peak in incidence of symptomatic temporomandibular joint disk displacement during
      adolescence for both genders. Teenage girls were found to run a risk of
      developing disk displacement that is three times greater than the risk for
      teenage boys, and girls were found to run a risk during puberty that is four
      times greater than their risk later in life. The age at onset of the condition
      did not differ between genders. Both female and male subjects reported the same
      degree of pain level. CONCLUSION: The results point to a teenage preponderance
      and a sexual dimorphism with respect to incidence of symptomatic
      temporomandibular joint disk displacement.

PMID- 9540082
TI  - Do temperature and atmospheric pressure affect the incidence of serious
      odontogenic infection?
AB  - OBJECTIVE: The purpose of this study was to investigate the popular belief that
      the incidence of odontogenic cellulitis is weather-related. Two meteorologic
      parameters were examined: temperature and atmospheric pressure. STUDY DESIGN: To
      test the hypothesis being studied, a retrospective cohort study design was used.
      Medical reports of all patients with serious odontogenic cellulitis who were
      treated at the Salpetriere University Hospital between January 1, 1995, and
      December 31, 1995, (a total of 301 cases) were evaluated in relation to the
      weather. Hypothesizing that the incidence of odontogenic cellulitis was constant
      over a period of 1 year, the authors calculated the probability of observed
      incidence for each month over a 12-month period. The mean number of cases of
      odontogenic cellulitis (+/- standard error of the mean) for days on which (1) the
      temperature was within the same 2 degrees -C (3.6 degrees -F) interval and (2)
      the atmospheric pressure was within the same 3-hPa (2.25-mmHg) interval was also
      calculated. RESULTS: When the monthly incidence of odontogenic cellulitis and
      either the average temperature or the average atmospheric pressure for each month
      were examined together, fluctuation in the former seemed to be independent of the
      latter. Similarly, when we calculated the mean number of cases of odontogenic
      cellulitis for several intervals of temperature and atmospheric pressure without
      taking the calendar into account, no direct relationship could be observed.
      CONCLUSION: The results of the study suggest that the occurrence of odontogenic
      cellulitis is not influenced by the weather, at least insofar as weather is
      measured by temperature and atmospheric pressure.

PMID- 9540092
TI  - Endodontic working length assessment. Comparison of storage phosphor digital
      imaging and radiographic film.
AB  - OBJECTIVE: This study compared the difference in interpretation of the position
      of endodontic file tips between two imaging systems: photostimulable storage
      phosphor luminescence imaging versus radiographic film. STUDY DESIGN: Thirteen
      patients were selected at random. Preoperative and trial file length radiographs
      were made with a dual image receptor composed of a Digora Digital Imaging Plate
      and a piece of Ektaspeed Plus film. Exposure techniques for E-speed film were
      used. Root length and file length measurements were made from digital images with
      the Digora system's measuring tools. Measurements were also made on radiographic
      film with a 7 x measuring magnifier. Root length, file length, and their
      difference were compared for both film and digital images. RESULTS: Differences
      were found to be less in digital than in film images. Photostimulable storage
      phosphor luminescence imaging performed similarly to Ektaspeed Plus film for
      measuring root lengths, but file tip positions (especially of small file sizes)
      were difficult to visualize with E-speed film. CONCLUSIONS: The smaller
      difference between file tip and root apex found with digital imaging suggests
      that this technique is more accurate to assess trial file length. This imaging
      modality for assessing file positions during root canal treatment may be
      beneficial to the practitioner.

PMID- 9540084
TI  - Primary hyperparathyroidism presenting as a giant-cell epulis.
AB  - The case of a giant-cell epulis as an initial feature of primary
      hyperparathyroidism is presented. A 58-year-old woman appeared for dental
      treatment with a buccal alveolar swelling that was confirmed by means of biopsies
      to be a multinucleated giant-cell lesion. High calcium levels warranted
      investigation for a parathyroid adenoma, which was located in an ectopic position
      and surgically removed. This case delineates the importance of referring patients
      with oral lesions of doubtful cause to specialists for further diagnostic workup.

PMID- 9540088
TI  - Autotransplantation for treatment of regional odontodysplasia. Case report with 6
      year follow-up.
AB  - Regional odontodysplasia is an uncommon dental malformation with characteristic
      clinical and radiographic findings. Affected teeth appear discolored with
      irregularly shaped surfaces. Radiographically wide pulp chambers and thin poorly
      defined hard tissue outlines are typical features. This report describes a 9-year
      old girl with recurrent and recalcitrant periapical infections as a result of
      unilateral mandibular odontodysplasia. With a 6-year follow-up, this is the
      longest documented case of regional odontodysplasia treated by tooth
      autotransplantation.

PMID- 9540091
TI  - Apical extent of rotary canal instrumentation with an apex-locating handpiece in
      vitro.
AB  - PROBLEM: The Tri Auto ZX (J. Morita Co., Kyoto, Japan) is a cordless endodontic
      handpiece with a built-in apex locator that is programmed to reverse the
      direction of rotation when the file reaches a predetermined apical level or when
      torque becomes excessive. OBJECTIVE: The purpose of this investigation was to
      examine the apical extent of rotary canal instrumentation and the ability to
      maintain apical constriction with the Tri Auto ZX at different automated
      settings. STUDY DESIGN: In 60 extracted teeth, canals were measured to the apical
      constriction, first visually and then electronically with the Tri Auto ZX; then
      they were instrumented with nickel titanium rotary files. For the
      instrumentation, the automatic apical reverse mechanism of the handpiece was set
      to 1, 1.5, or 2; these settings correspond to different distances from the apical
      foramen. Instrumentation was carried out apically until rotation was reversed by
      the automatic apical reverse function; the instrumented length was then measured,
      and the canal was filled with gutta-percha and sealer. The integrity of the
      apical constriction was assessed by exposing the apical 4 mm of the canal and
      observing the dentin-cementum junction. Paired t-tests were used to compare the
      visually measured length, the electronically measured length, and the
      instrumented length for each tooth. RESULTS: On average, the electronically
      measured length was 0.54 mm shorter than the visually measured length (p < 0.05).
      When the automatic apical reverse mechanism's setting was 1, the instrumented
      length was 0.1 mm shorter than the electronically measured length; when the
      setting was 1.5, the instrumented length was 0.36 mm shorter than the
      electronically measured length (p < 0.01). Results were inconsistent when the
      setting was 2. CONCLUSION: Instrumentation with the automatic apical reverse
      feature set at 1 consistently approximated the apical constriction; however, the
      constriction was frequently enlarged.

PMID- 9540089
TI  - Regional odontodysplasia. Report of two cases.
AB  - Two cases of regional odontodysplasia in girls are reported; one affected the
      lower incisors, and the other the left maxilla. The first case was
      radiographically followed over a 6-year period, during which time the ghost teeth
      exhibited significant dentin formation, along with a resultant decrease in pulp
      size and relative normalization of the radicular anatomy. The second case
      involved the deciduous molars and the first permanent molar. In addition to tooth
      alterations, both cases exhibited many odontogenic epithelial islands and
      extensive areas of calcification in the mucosa. Diagnosis, causes, and treatment
      are discussed in the light of recent data.

PMID- 9540086
TI  - Chondromyxoid fibroma of the jaws. Case report and review of the literature.
AB  - Chondromyxoid fibroma is a benign tumor of bone that is characterized by
      chondroid and myxoid differentiation and by ultrastructural and
      immunohistochemical evidence of chondral origin. It is rare in the jaws and skull
      bones, where only about 2% of all cases have been reported. A review of the 20
      acceptable gnathic cases in the literature and of the current case revealed both
      a higher incidence in the mandible (76%) than in the maxilla (24%) and an equal
      sex distribution. The sites of occurrence in both jaws are compatible with origin
      from developmental cartilaginous remnants. The controversies regarding malignant
      transformation and therapeutic approach are addressed.

PMID- 9540083
TI  - Gland atrophy following retrograde injection of methyl violet as a treatment in
      chronic obstructive parotitis.
AB  - OBJECTIVE: The purpose of this study was to evaluate the clinical effectiveness
      of retrograde injection of 1% methyl violet as a treatment for chronic
      obstructive parotitis. STUDY DESIGN: Sixteen patients with chronic obstructive
      parotitis were treated with retrograde injection of 1% methyl violet.
      Pretreatment evaluation and assessment of the treatment effect were performed by
      clinical and imaging methods, including sialography and sonography of the treated
      glands. RESULTS: Clinical symptoms following treatment included initial acute
      swelling and then a decrease in parotid swellings; the final outcome was a
      clinical cure of the affected glands characterized by disappearance of all
      symptoms, absence of secretion, and complete obliteration of the main duct
      orifice. Posttreatment imaging showed total atrophy of the diseased glands.
      CONCLUSION: Retrograde injection of 1% methyl violet caused total atrophy of the
      diseased glands and brought about complete relief in all 16 patients, with no
      detectable side effects.

PMID- 9540085
TI  - Paroxysmal hemicrania. Case studies and review of the literature.
AB  - Paroxysmal hemicrania is a vascular-type headache that is characterized by short
      bouts of severe unilateral pain in the area of the orbit and temple. A chronic
      and episodic form that has been described is similar to cluster headache and
      reflects a distinctive temporal pattern. Signs associated with paroxysmal
      hemicrania include ipsilateral conjunctival injection and tearing with nasal
      congestion and rhinorrhea. The condition's absolute response to indomethacin
      pharmacotherapy differentiates paroxysmal hemicrania from cluster headache.
      Typical symptoms usually make for a relatively straightforward diagnosis of
      paroxysmal hemicrania, but it may masquerade as pulpitic or temporomandibular
      joint-related pain and may even herald systemic disease or malignancy. Paroxysmal
      hemicrania is a rare syndrome; 111 cases have been reported in the literature
      thus far. All of these cases have been reported by "headache specialists"; no
      cases of paroxysmal hemicrania were found in the dental literature. In this
      review, a relatively large series of seven new cases is reported; all seven were
      seen in an orofacial pain clinic.

PMID- 9540087
TI  - Multiple macrodonts with odontoma in a mother and son--a variant of Ekman
      Westborg-Julin syndrome. Report of a case.
AB  - A case of multiple macrodonts with a complex odontoma in a mother and son is
      reported. This condition is thought to represent a variant of the Ekman-Westborg
      Julin syndrome. The authors discuss the relationship between macrodontia and
      odontoma, and the involvement of hereditary factors is suggested.

PMID- 9540090
TI  - The role of integrin beta 1 in human dental pulp cell adhesion on laminin and
      fibronectin.
AB  - OBJECTIVE: This study is to identify the expression of integrin beta 1 in human
      dental pulp cells and the role of integrin beta 1 in pulp cell adhesion on
      extracellular matrix protein laminin and fibronectin. STUDY DESIGN: Immunoblot
      detection of integrin beta 1 in human pulp cells was with the use of monoclonal
      anti-beta 1 antibody. Dental pulp cell adhesion assay on extracellular matrix
      protein laminin and fibronectin and blocking cell adhesion was performed with
      monoclonal anti-beta 1 antibody. RESULT: Integrin beta 1 was identified in human
      dental pulp cells. Pulp cells adhered and spread on both laminin and fibronectin.
      Monoclonal anti-beta 1 antibody inhibited human dental pulp cells adhesion on
      laminin but not on fibronectin. CONCLUSIONS: Integrin beta 1 was expressed on
      human dental pulp cells and mediated cell adhesion on laminin. Human dental pulp
      cells also adhered on fibronectin but the adhesion was not regulated by beta 1
      integrin.

PMID- 9540094
TI  - Morphologic operations used to distinguish between two patient populations
      differing in periodontal health.
AB  - OBJECTIVES: This study was conducted to determine whether morphologic operation
      procedures applied to digitized, non-standardized, clinical radiographs of
      mandibular alveolar bone could be used to distinguish between a population of
      patients diagnosed with periodontitis and a population of patients either
      diagnosed with gingivitis or having healthy gingivae. STUDY DESIGN: Two groups,
      one consisting of 29 patients who either had healthy gingivae or had been
      diagnosed with gingivitis and the other consisting of 32 patients who had been
      diagnosed with periodontitis, were compared. Pre-existing clinical radiographs
      were digitized, and for each patient three to six regions of interest were placed
      on an image of the mandibular posterior region of the interdental bone. The
      regions of interest were processed under two morphologic-operations protocols,
      and a mean density (referred to as an MO number) was calculated for each patient.
      With paired t-tests, the resulting MO numbers for the two groups were compared.
      RESULTS: The two populations were statistically different (p < 0.05). CONCLUSION:
      The results of this study indicate that morphologic operations have the potential
      to differentiate between patient groups differing in periodontal health.

PMID- 9540096
TI  - [Complex injuries--complex treatment algorithms].

PMID- 9540093
TI  - New cephalometric images with a workstation. A preliminary report.
AB  - OBJECTIVE: This study was designed to test the feasibility of several types of
      enhancements for cephalometric computed radiographs through use of the Fuji
      Computed Radiography system (Fuji Photo Film Corp., Tokyo, Japan). STUDY DESIGN:
      The material consisted of four lateral cephalograms made with the Fuji Computed
      Radiography system that were enhanced by varying the gradient levels before
      processing by means of both A-type (straight gradation) curves and workstation
      type (peaked) curves. The four workstation-type images were set with optical
      densities at the peak of the curve at 1.5, 1.7, 1.9, and 2.1. Ten observers
      evaluated eight anatomic landmarks comparing pairs of workstation-type images.
      The best workstation-type image was then compared with the A-type image for the
      same landmarks. RESULTS: For the four workstation-type images the best
      visualization of the anatomic landmarks was seen with workstation-type image 3,
      which had a maximum optical density of 1.9. Image 3 was also superior to the
      results of A-type image processing for most of the landmarks. CONCLUSION: Image
      enhancement with the application of a computed radiography system is effective
      for study of lateral cephalograms.

PMID- 9540097
TI  - [Complex trauma of the shoulder girdle].
AB  - Complex injuries of the shoulder require differentiated management. Interestingly
      there is a relative lag of warranted information on this subject. Generally the
      different lesions are discussed separately. However it is not acceptable to
      simply add the standard diagnostic and therapeutic measures, because major
      tactic, strategic and rehabilitation incompatibilities could occur. Diagnostic
      and therapeutic difficulties are frequent for the following injuries: complex
      proximal humerus dislocation fractures, dislocation fractures with associated
      lesions of the rotator cuff, posterior dislocation fractures, peri- and
      intraarticular segmental fractures and fractures or dislocations associated with
      major neurovascular lesions. Increased awareness of the most relevant diagnostic
      and therapeutic aspects should contribute to optimize treatment protocols.

PMID- 9540095
TI  - The role of panoramic radiography in determining an increased risk of cervical
      atheromas in patients treated with therapeutic irradiation.
AB  - PURPOSE: Therapeutic irradiation of the neck is a common component of treatment
      for those with carcinoma of the oral cavity, pharynx, and larynx. Such
      irradiation, however, has been implicated as the cause of accelerated
      atherosclerosis of the cervical carotid artery and subsequent stroke. Panoramic
      radiography, previously shown to be capable of identifying carotid artery
      atherosclerosis in non-irradiated individuals, was used to assess the carotid
      vasculature of patients who had been treated for cancer with therapeutic
      irradiation. METHODS: The panoramic radiographs of 33 male subjects who had
      received therapeutic irradiation (> or = 50 Gy) to the neck 30 or more months
      previously were assessed for the presence of calcified carotid artery
      atherosclerotic lesions. Age-matched controls, similarly liable for oropharyngeal
      malignancy and atherosclerosis by virtue of their medical and habitual risk
      factors (hypertension, smoking, obesity) were assessed in a like manner. RESULTS:
      The panoramic radiographs of the irradiation-treated subjects (age range, 32 to
      84 years; mean age, 66.1 years) showed that 21% (7 of 33 subjects) had calcified
      atherosclerotic lesions. The mean age of these seven subjects was 64.6 years;
      four had unilateral lesions and three had bilateral lesions. The radiographs of
      the control subjects showed that 4.7% (5 of 107 subjects) had calcified
      atherosclerotic lesions. The mean age of these five subjects was 67; three had
      unilateral lesions and two had bilateral lesions. The lesions seen in the two
      populations had similar morphologic appearances. The discrete radiopaque
      calcifications were located within the soft tissues of the neck, approximately
      2.5 cm inferior-posterior to the angle of the mandible. CONCLUSIONS: Subjects who
      had received therapeutic irradiation of the neck had a statistically higher risk
      (p = 0.007, according to Fisher's Exact Test) of the development of calcified
      carotid artery atherosclerotic lesions than age-matched, risk-matched, non
      irradiated control subjects. These lesions can be detected on routine panoramic
      radiographs.

PMID- 9540102
TI  - [Spondylolysis and spondylolisthesis. Diagnosis and therapy].

PMID- 9540098
TI  - [Complex trauma of the hand].
AB  - The hand is very exposed to injuries in the daily man's work. The multiple
      functions of the hand are based on vitality, sensibility, motor function and
      stability. In severe hand injuries the functional results of the repair are often
      very poor. In a complex injury of the hand we are faced with the damage of the
      soft tissue and bone and the loss of vitality and function of the hand. The cause
      of hand injuries are mainly a crush trauma or the rotating saw. Basically, we
      recommend an extended primary repair. After the radical debridement we have to
      reconstruct the damaged structures. We start doing the osteosynthesis and
      stabilization of the joints. Thereafter, suturing of extensor and flexor tendons.
      Then, we do the microsurgical reconstructions of vessels and nerves. In case
      tendons and bones are exposed we have to cover the defect with a pedicled or a
      free flap. In a long ischemic time we have to change our concept and do the
      reconstruction of the vessels first. Our results in vitality and sensibility are
      listed. In the result of a complex hand injury each single functional restoration
      is very important. Therefore, it is necessary that severe hand injuries are
      treated at well established centres for hand surgery.

PMID- 9540101
TI  - [Prospects of tissue transfer and tissue culture].
AB  - Posttraumatic lesions of joints and extremities create a major challenge for an
      anatomic plastic reconstruction. The experimental and clinical progress in the
      field of tissue engineering, immunosuppression of allografts and xenografting
      including methods of genetic engineering provides a potential basis for the
      reconstruction of whole limbs or anatomical segments with living tissue.

PMID- 9540100
TI  - [Complex injuries of the pelvis and acetabulum].
AB  - Injuries of the joints of the pelvis and of the acetabulum are still a problem
      even today. When the joints of the pelvis are damaged the risk of complicated
      pelvic injuries, that is to say pelvic injuries with damage to the soft tissues
      in and around the pelvis, is increased threefold. The lethality, the overall
      gravity of the injuries, the probability of haemorrhagic complications and the
      proportion of associated pelvic injuries are also increased. Even when anatomical
      reconstruction of the lower limb girdle is achieved, long-term secondary
      conditions such as pain and genitourinary and neurological sequelae frequently
      persist. Complicated pelvic injuries, i.e. pelvic injury with concomitant damage
      to organs and soft tissues in the pelvis and pelvic injuries with ipsilateral
      femoral fracture (floating hip) are special cases. Haemodynamic stabilization of
      the patient and the treatment of organic lesions must be the first priorities in
      the interdisciplinary therapy. Even when these priorities are correctly observed,
      the lethality is almost three times as high as in the case of pelvic injuries not
      involving soft-tissue damage. Acetabular fractures are a particular challenge
      even compared with other joint fractures. Operative treatment with anatomical
      joint reconstruction and stable internal fixation has been shown to have the best
      results. In addition to the type of fracture and the personal experience of the
      surgeon concerned, such fracture-specific factors as the presence of further
      fractures of the posterior wall, comminuted fractures, joint depression fractures
      and intra-articular fragments increasingly play a part. The long-term result
      worsens with increasing number of these additional pathologies. The primary
      cartilaginous damage caused by the accident seems to have a considerable
      influence on the long-term result following acetabular fractures.

PMID- 9540099
TI  - [Complex injuries of the spine].
AB  - 3 different types of complex spinal trauma are defined: Type I means a multilevel
      contiguous or non contiguous unstable injury, type II is described as a spinal
      injury with concomitant thoracic or abdominal lesion, type III stands for the
      coincidence of spinal injury and polytrauma. Overlapping of different types
      occurs. Type I: The incidence amounts according a german multicenter study to
      about 2.5%. Multilevel injuries need to be stabilized for a long distance from
      posterior. With a thorough analysis the segments to be fused are determined. Type
      II: The leading thoracic injury is a lung contusion which occurs in up to 50% of
      the cases. A CT scan of the thorax during the first diagnostic screening is
      recommended. Early reduction and stabilization from posterior should be aimed at.
      During the first two weeks anterior procedures are contraindicated. Abdominal
      injuries are to be found in 3-4% of all spinal injuries. All organs could be
      affected. A typical constallation is the "seat-belt syndrome" with lesions of the
      upper abdominal organs and a flexiondistraction injury of the upper lumbar spine.
      The main problem is to make the diagnosis of both components initially. Most of
      the patients may be treated in one operation by first taking care of the
      abdominal injury and than stabilizing the spine. The prognosis of this
      combination is favorable. Type III: In 17-18% of all polytraumatized patients
      lesions of the spine are to be diagnosed. From these only one third need surgical
      care. From 680 patients with operatively treated fractures of the thoracolumbar
      junction 6.2% were polytraumatized according to the multicenter study mentioned
      above. The risk of missing a spinal injury in polytrauma totals approximately
      20%. Surgical stabilization should be performed in the primary phase (day-1
      surgery). Additional injuries, potentially time consuming operations with a high
      blood loss sometimes necessitate a different approach. Non stabilized spinal
      injuries apparently do not have the same negative effect on the whole organism as
      long bone fractures. In the early phase of treatment on the C-spine only anterior
      procedures and on the thoracolumbar spine only posterior techniques should be
      applied.

PMID- 9540105
TI  - Synthesis, chemical and pharmacological properties of some 4-aryl-1,2,3,4,5,6,7,8
      octahydroquinazoline-2,5-diones.
AB  - A series of 4-aryl-1,2,3,4,5,6,7,8-octahydroquinazoline-2,5-diones were
      synthesized by condensing urea with 1,3-cyclohexanedione and appropriate aromatic
      aldehydes according to the Biginelli reaction. The structures of the compounds
      were confirmed by elementary and spectroscopic analysis. The compounds
      synthesized were tested in vitro for their calcium antagonistic activities. BaCl2
      induced contractions of rat ileum were inhibited dose-dependently. Compounds 3-8
      exerted weak calcium antagonistic activity on smooth muscles compared with the
      standard nicardipine.

PMID- 9540103
TI  - Antitumour drug design: DNA-binding ligands, which inhibit the topoisomerase I.
AB  - DNA-enzymes, which are overexpressed in special tumour cells represent in general
      interesting targets for an antitumour drug design. In this context a survey about
      the function and the biochemical mechanistic aspects of topoisomerases is given.
      In the last years detailed studies in medicinal chemistry (structure activity
      relationships) revealed that first of all topoisomerase I inhibitor will become
      an attractive class of promising and perhaps more selective drugs in cancer
      chemotherapy. Thus, in the present review actual aspects about drug design
      developments of topoisomerase I inhibitors are presented. Moreover some recent
      results about new lead substances, some structure activity relationships and some
      clinical aspects are discussed.

PMID- 9540106
TI  - [Synthesis and properties of 5(4,6-diphenyl-2-pyrimidin-2-yl)-1,2,4-triazolin-3
      thione and derivatives ].
AB  - By treatment of 4,6-diphenyl-pyrimidin-2-carboxyl chloride (1) with
      thiosemicarbazide the acylthiosemicarbazide 3 has been synthesized. Compound 3
      could also be obtained by action of hydrazide on potassium thiocyanate. 5-(4,6
      Diphenyl-pyrimidin-2-yl)-1,2,4-triazolin-3-thione (5) could be prepared either by
      basecatalyzed cyclization of acylthiosemicarbazide or by the reaction of methyl
      4,6-diphenyl-pyrimidin-2-carboxylate with thiosemicarbazide in the presence of
      sodium methoxide. Alkylation of the 1,2,4-triazolin-3-thione 5 with chloroacetic
      acid resulted in formation of the S-carboxymethyl derivative 6. On heating, with
      a mixture of glacial acetic acid/acetic anhydride, compound 6 afforded 6-(4,6
      diphenyl-pyrimidin-2-yl)thiazolo[3,2-b]-1,2,4-triazol-3(2H) -one (7).
      Condensation of 7 with aromatic aldehydes yielded 2-arylidene-6-(4,6-diphenyl
      pyrimidin-2-yl)thiazolo[3,2-b]-1,2,4-+ ++triazol-3(2H)-ones, which could also be
      prepared by treatment of the S-carboxymethyl derivative 6 with an appropriate
      aldehyde in the presence of acetic acid and acetic anhydride. Some of the
      synthesized compounds possess a weak antiinflammatory activity.

PMID- 9540107
TI  - Photoreactivity of biologically active compounds, XIV: influence of oxygen on
      light induced reactions of primaquine.
AB  - The influence of molecular oxygen and oxygen radicals on the photoreactivity of
      the antimalarial drug primaquine (PQ) has been investigated. Oxygen is directly
      involved in photodecomposition of the drug. Flushing with helium gas prior to and
      during irradiation to suppress the oxygen level of the medium, retards the
      degradation rate of PQ (followed by HPLC) and leads to the formation of only two
      degradation products (identified by MS) compared to eight main- and several minor
      products under normal atmospheric conditions. Flushing with oxygen gas prior to
      and during irradiation to increase the oxygen content of the medium accelerates
      the degradation rate of PQ. PQ produces oxygen radicals (hydroxyl and superoxide)
      during photolysis, while the photoproducts of PQ seem likely to induce singlet
      oxygen formation (detected by addition of radical scavengers). Sensitization
      reactions involving singlet oxygen lead to decomposition of PQ (followed by
      HPLC). On the basis of our results, photochemical reaction mechanisms of PQ are
      postulated and discussed. At physiological conditions (aqueous, neutral pH,
      oxygen rich) PQ has a large potential to decompose after light absorption. The
      photoreaction seems to be initiated at the quinoline nitrogen. The ability to
      form an intramolecular hydrogen bond seems to be essential for the luminescence
      properties of the drug. Phosphorescence lifetime of PQ is about 5 microseconds.
      Fast chemical reactions may occur from the short-lived triplet state of the drug,
      but the excited compound can diffuse only a limited distance prior to
      deexcitation. This can be important concerning light-induced adverse effects
      which may appear after medication with PQ.

PMID- 9540110
TI  - Antidepressant activity of new hetero[2,1]benzothiazepine derivatives.
AB  - A number of thieno and pyrazolo[2,1]benzothiazepine derivatives as well as
      several synthetic intermediate compounds were tested for acute toxicity and
      antidepressant activity in mice. Some of these compounds were effective in the
      tetrabenazine and Porsolt tests.

PMID- 9540104
TI  - Syntheses of novel pyrazolomorphinans and their binding to mu- and kappa-opioid
      receptors.
AB  - A number of novel pyrazolomorphinans have been synthesized in excellent yields by
      the reaction of the enolic morphinan diketones 6 with various hydrazines.
      Hydrazine dihydrochloride led to the N-unsubstituted tautomeric pyrazoles 7a in
      equilibrium with 9a and 8a in equilibrium with 10a which could not be separated.
      Arylhydrazines on the other hand furnished the regioisomeric pyrazolomorphinans 7
      and 9 as well as 8 and 10, which could be isolated and characterized. The
      structures of the new compounds were clarified by their spectra, the assignment
      of the regioisomeres was achieved by determination of NOE enhancements. Compounds
      6a, 7c, 8b and 10c have been evaluated for their affinity at mu and kappa opioid
      receptors in radioligand binding assays. Their ability to inhibit [3H] DAMGO
      binding to mu and [3H] U 69,593 binding to kappa opioid receptors has been found
      to be comparable with that of codeine.

PMID- 9540108
TI  - Antineoplastic and cytotoxic activity of beta-alkylamino-(para
      substituted)propiophenone and beta-alkylamino-(6-methyl)-naphthone derivatives in
      murine and human tissue culture cells.
AB  - The beta-alkylamino(para-substituted)propiophenone and beta-alkylamino-(6
      methyl)naphthone derivatives were evaluated for their antineoplastic effects in
      vitro in CF1 mice at 8 mg/kg/day intraperitoneal for 9 days. A number of these
      agents showed over 70% inhibition of Ehrlich ascites carcinoma growth. In in
      vitro cytotoxicity assays, these agents significantly inhibited the growth of a
      number of cancer cell lines from both human and murine origins. Some agents
      showed more activity than several standard anticancer drugs against certain cell
      lines. Three analogs, beta-(4-methyl)piperidino-(para-methyl)propiophenone (4),
      beta-piperidino-(para-ethoxy)propiophenone (13), and beta-hexamethyleneimino
      (para-ethoxy)-propiophenone (14), were selected for mode of action studies and
      all showed significant inhibition of DNA and RNA syntheses at 100 microM after 60
      min incubation. However, the most significant site of action was the inhibition
      of the activity of dihydrofolate reductase.

PMID- 9540113
TI  - Displacement of [3H]-L-glutamate in rat brain membranes by metabolic dynorphin
      fragments.

PMID- 9540115
TI  - Growth factors released from bone marrow are promising tools in orthopedic
      surgery.

PMID- 9540109
TI  - Potential anxiolytic-like activity of some amino acid derivatives.
AB  - Three derivatives of amino acids: (R)-Ac-Pro-BZA (1), Ac-beta Ala-BZA (2) and (S)
      Ac-Arg(NO2)-BZA (3) were evaluated as potential anxiolytics. In the conflict
      drinking test in rats used as a model of anxiety, the tested compounds exhibited
      anxiolytic-like activity. Compounds 1 and 2 administered in doses of 50-100 mg/kg
      produced an anticonflict effect in a dose-dependent manner. A distinct effect is
      observed after dose of 100 mg/kg of 1 and 2, comparable to those induced by 10
      mg/kg of diazepam. The anticonflict effect of 3 was weak and dose independent. It
      was revealed only in one mean dose (50 mg/kg) but not in the higher doses.

PMID- 9540117
TI  - Tyrosine kinase participates in phosphorylation of the Ro60 ribonucleoprotein.
AB  - Studies of Ro ribonucleoprotein are important in rheumatology, since anti-Ro
      antibodies are probably involved in the pathogenesis of congenital heart block
      and subacute cutaneous lupus erythematosus. In addition, the phosphorylation
      dephosphorylation cycle modulates binding of ribonucleoproteins to RNA, a process
      that might affect the antigenicity and function of the Ro protein. The present
      study was designed to determine whether Ro can be phosphorylated by tyrosine
      kinase. To answer this question, synchronized HEp-2 cells were phosphorylated in
      vivo with exogenous 32P, and Ro ribonucleoprotein previously subjected to
      metabolic radiolabeling was immunoprecipitated by monoclonal anti-Ro antibodies
      and examined by SDS-PAGE and autoradiography. The main results were as follows:
      first, Ro ribonucleoprotein was phosphorylated in vivo; second, Ro was found to
      have phosphorylable tyrosine residues; third, tyrosine kinase participated in the
      phosphorylation of Ro; and fourth, phosphorylation did not change the recognition
      pattern of Ro by anti-Ro antibodies. In conclusion, Ro60 is phosphorylated by
      tyrosine kinase.

PMID- 9540112
TI  - Cyclodextrins as co-enhancers in dermal and transdermal drug delivery.

PMID- 9540114
TI  - Effect of fluvoxamine on the level of beta-endorphin in the sera and nervous
      tissue of rats.

PMID- 9540111
TI  - Identification of a pill for eye-diseases from traditional Chinese medicine.

PMID- 9540116
TI  - Anti-Ro(SS-A)

PMID- 9540123
TI  - Giant cell tumors of bone.
AB  - Giant cell tumors of bone are uncommon primary bone tumors that occur in young
      adults and predominantly affect the ends of long bones, most notably the distal
      femur and proximal tibia. The lesion is seen on radiographs as a multilobed lytic
      defect with a sharply-defined transition zone, cortical thinning and in some
      instances a trabeculated appearance. The clinical behavior ranges unpredictably
      from quiescence to marked local aggressiveness with a tendency to local
      recurrence. The diagnosis depends on obtaining a histologic specimen, which
      usually shows benign tissue. However, a few apparently benign giant cell tumors
      of bone are capable of producing distant lesions, especially in the lung.
      Primarily or secondarily malignant giant cell tumors of bone are exceedingly
      rare. Treatment relies chiefly on excision of the lesion, which should be as
      complete as possible since the risk of recurrence is more closely dependent on
      the completeness of tumor removal than on radiologic and histologic evidence of
      aggressiveness. Histologic sections show numerous osteoclasts admixed with
      hematopoietic or mesenchymal mononuclear cells. The mesenchymal cells are the
      tumorous component of the lesion and induce formation of a large number of
      osteoclasts.

PMID- 9540125
TI  - Sacral perineurial cyst with ossification of the arachnoid membrane.
AB  - A case of sacral perineurial cyst with ossification of the arachnoid membrane
      discovered intraoperatively is reported. We are not aware of any similar cases in
      the literature.

PMID- 9540118
TI  - A retrospective review of 115 cases of surgically-treated trapeziometacarpal
      osteoarthritis.
AB  - The trapeziometacarpal joint is among the main targets for osteoarthritis at the
      hand. The objective of surgical treatment is to obtain a painless, stable, and
      mobile joint. One hundred fifteen cases treated either by a GUEPAR prosthesis (n
      = 90; group A) or by excision of the trapezium followed by ligament
      reconstruction and tendon interposition (n = 25; group B) were studied
      retrospectively. The choice between the two procedures was based on a number of
      clinical and radiological criteria. Of the 90 group A patients, 79 were
      reevaluated, after a mean follow-up of 5.75 years. Clinical results were good in
      92% of cases. Loosening of the cup was seen in seven cases, of which three (3.8%)
      were treated by implantation of a Swanson prosthesis within three years of the
      first procedure. Six patients had loosening of the metacarpal component only,
      which was stable over time and had no adverse effect on clinical results. Of the
      25 group B patients, 19 were reevaluated, after a mean follow-up of 3.5 years.
      Clinical results were good in 18 cases; the height of the scaphometacarpal space
      decreased by a mean of 51% versus its preoperative value. We conclude that the
      GUEPAR prosthesis provides good results with a low revision rate and deserves to
      be widely used in patients with a trapezium of at least 7 mm in height.
      Indications for the excision-reconstruction-interposition procedure include
      severe osteoarthritis, trapezium height less than 7 mm, younger age, and
      intensive hand use.

PMID- 9540126
TI  - Can talc mixed with heroin induce systemic sclerosis?

PMID- 9540128
TI  - Early and late sympathetic activation in hypertension.
AB  - In several experimental animal models of hypertension, sympathetic factors have
      been shown to be involved in the development and/or maintenance of high blood
      pressure. Although the information available on this issue in man is more scarce,
      recent evidence clearly indicates the participation of adrenergic mechanisms in
      the early and late phases of the hypertensive process. In addition, several
      cardiovascular risk factors frequently associated with hypertension, such as
      obesity, insulin-resistance, cigarette smoking, and the atherogenic process, are
      also characterized by alterations in sympathetic cardiovascular drive. This
      contributes to a further activation of the sympathetic nervous system thus
      favoring the development of the end organ damage (e.g. cardiac and vascular
      hypertrophy) associated with the hypertensive state.

PMID- 9540122
TI  - The situation of rheumatology today in Germany.

PMID- 9540120
TI  - Management and cost of care for low back pain in primary care settings in France.
AB  - We conducted a prospective observational study during the winter of 1994-1995 in
      a representative national sample of 2,406 patients aged 18 to 65 years seen in
      primary care settings for acute low back pain of less than 48 hours' duration.
      The following data were collected: demographic, social and clinical
      characteristics at inclusion; treatments prescribed throughout the episode,
      functional impairment and restriction of usual activities. These data were used
      to evaluate direct costs (health costs) and indirect costs (sickness payments).
      The sex ratio was predominantly male (60.4%), 80% of patients were economically
      active, mean age was 43 +/- 11.7 years, and most patients (76%) had a history of
      low back pain. Management consisted primarily of rest (bedrest, 32%; rest at
      home, 61%) and pharmacotherapy (mainly analgesics, nonsteroidal antiinflammatory
      drugs and muscle relaxants; mean number of drugs per patient, 3.2). Imaging
      studies were obtained in 34% of cases and physical therapy was prescribed in 30%.
      Referral and hospitalization rates were 5.4% and 0.8%, respectively. Among
      economically active patients, 82% were put on sick leave, for a mean duration of
      8.4 +/- 4 days and 18.6% were reported as having work-related low back pain. The
      mean cost of outpatient care for the episode of low back pain was 1,021 French
      francs (FF), most of which was contributed by physical therapy (41.6%),
      physicians' fees (23.9%) and investigations (16%). Mean sickness payments were
      821 FF per patient in the economically active subgroup and 523 FF per patient in
      the overall study population.

PMID- 9540127
TI  - Hypertension-induced congestive heart failure.
AB  - Arterial hypertension used to be the most common cause of congestive left
      ventricular failure. With the availability and common use of antihypertensive
      treatment the incidence and prevalence of hypertension-induced left ventricular
      failure has gradually declined. Today congestive heart failure due to underlying
      coronary heart disease is by far more common than the hypertension-induced
      variety. The effect of treatment of left ventricular failure in recent years, in
      particular with angiotensin converting enzyme inhibitors and carvedilol, has been
      impressive.

PMID- 9540119
TI  - CT scan texture analysis of the distal radius: influence of age and menopausal
      status.
AB  - OBJECTIVES: To gain information on bone architecture by performing bone texture
      analysis in a sample of women covering a broad age range. PATIENTS AND METHODS:
      We studied 29 healthy women aged 23 to 80 years (55 +/- 18 years), 19 of whom
      were postmenopausal. None was taking drugs known to influence bone mass or bone
      metabolism. Computed tomography of the nondominant distal radius was performed
      with 1 mm slice thickness and 1 mm gap. Four consecutive coronal and four
      consecutive axial sections were selected for each patient and entered into a PC
      type computer. Bone texture was evaluated using grey level run length analysis
      (five parameters), differential local variation analysis (four parameters),
      fractal analysis (two parameters), trabecular network extraction and three
      dimensional relief characterization. The mean of each study parameter for the
      four coronal sections and for the four axial sections was calculated.
      Absorptiometry was done in 16 patients. RESULTS: Linear correlations with age
      were strongest (P < 0.001) for parameters measured on coronal sections by
      trabecular network extraction, i.e., trabecular bone volume (r = -0.68),
      trabecular plate separation (r = -0.65), total skeletal length (r = -0.71),
      number of nodes (r = 0.73), number of node-node segments (r = -0.74) and
      trabecular bone pattern factor (r = 0.71). Also, these parameters were
      significantly different between premenopausal women (33 +/- 9 years) and
      postmenopausal women (67.3 +/- 9 years). Correlations between bone mineral
      density and texture parameters were few in number and modest in strength,
      suggesting that the parameters measured may reflect bone structure rather than
      bone mass. CONCLUSION: Bone texture in women undergoes changes with advancing age
      that may reflect alterations in bone microarchitecture.

PMID- 9540129
TI  - Vascular remodeling and endothelial function in hypertensive patients: effects of
      antihypertensive therapy.
AB  - OBJECTIVE: To review studies of effects of antihypertensive agents on alterations
      in structure and function of small (resistance-size) arteries in hypertensive
      patients and in experimental hypertensive models, since these vessels may
      contribute to blood pressure elevation or to the complications of hypertension.
      MAIN OUTCOME MEASURES: The structure and endothelium-dependent relaxation of
      small arteries obtained in hypertensive humans from gluteal subcutaneous
      biopsies, and from different vascular beds in hypertensive rats, without and
      after antihypertensive treatment, and studied on a wire-myograph or as
      pressurized arteries, are described as reported in different studies. RESULTS:
      Treatment of spontaneously hypertensive rats (SHR) with angiotensin converting
      enzyme (ACE) inhibitors, calcium channel antagonists, angiotensin receptor
      antagonists and novel beta blockers such as carvedilol, has been shown to result
      in regression of the altered structure of small arteries in different vascular
      beds, in addition to improved endothelium-dependent relaxation. Several studies
      in hypertensive patients have now shown that treatment with some ACE inhibitors
      (cilazapril and perindopril) or extended release calcium channel antagonists
      (nifedipine GITS) induces similar effects in small arteries obtained from gluteal
      subcutaneous biopsies: both structure and endothelium-dependent relaxation
      improve under treatment. In contrast, hypertensive patients with equally well
      controlled blood pressure but treated with the beta blocker atenolol did not in
      any of three studies exhibit any improvement in the structure of small arteries
      or in endothelial function. CONCLUSION: Although treatment for at least one year
      with some ACE inhibitors and extended release calcium channel antagonists
      corrects the structure and endothelium-dependent relaxation of gluteal
      subcutaneous small arteries, it still remains to be determined whether this
      apparently beneficial effect beyond blood pressure lowering of these and other
      agents with vascular protective properties will result in reduced morbidity and
      mortality in hypertensive patients.

PMID- 9540130
TI  - Clinical consequences of the autonomic imbalance in hypertension and congestive
      heart failure.
AB  - The reduction of coronary mortality is not as large as one would expect from the
      observed blood pressure lowering in trials of antihypertensive medications. This
      is not surprising; hypertension is a complex disease where the high blood
      pressure is only one of numerous coronary risk factors. Sympathetic overactivity
      in hypertension, independent of the blood pressure, may be conducive to premature
      atherosclerosis by inducing insulin resistance and dyslipidemia. Through its
      trophic effect on blood vessels, sympathetic overactivity potentiates
      vasoconstriction. This, in turn, accelerates hypertension and the metabolic
      syndrome. The hypertrophy of small coronary arterioles decreases the coronary
      reserve and enhances coronary spasms. Tachycardia, which is due to increased
      sympathetic tone and a decreased parasympathetic tone, favors arrhythmias and
      sudden death in congestive heart failure and hypertension. Increased hematocrit
      is frequently found in male patients with hypertension, and high hematocrit is a
      predictor of coronary heart disease/thrombosis. The increase of hematocrit is in
      part due to an alpha adrenergic postcapillary venoconstriction. Enhanced
      sympathetic drive, insulin resistance and dyslipidemia have been demonstrated
      also in congestive heart failure, but the clinical importance of these findings
      is not fully understood.

PMID- 9540131
TI  - Treating hypertension--effect of treatment and cost-effectiveness in respect to
      later cardiovascular diseases.
AB  - A large number of prospective intervention trials have clearly demonstrated that
      drug treatment of hypertension lower cardiovascular morbidity and mortality. In
      the elderly, where treatment results in higher absolute decreases in morbidity
      and mortality, drug treatment is clearly cost-effective or even cost-saving in
      some groups of patients. Although the concept of treating hypertension is
      generally well accepted, a significant portion of patients remain insufficiently
      treated. In spite of major advances in the management of hypertension during the
      last decades, there is an excess morbidity and mortality in the hypertensive
      population. Thus, treatment is still imperfect, and a number of measures need to
      be taken in order to bring down cardiovascular risk in hypertensive patients to
      that of the normotensive population.

PMID- 9540121
TI  - Validation of the French version of the Dallas Pain Questionnaire in chronic low
      back pain patients.
AB  - OBJECTIVES: To translate and to validate the metrological properties of the
      Dallas Pain Questionnaire, an instrument designed to evaluate the impact of low
      back pain on four aspects of patients' lives: daily activities, work and leisure
      activities, anxiety/depression and social interest. METHODS: The Dallas Pain
      Questionnaire, originally in English, was translated into French. The
      metrological properties of the French version were investigated in a cohort of 59
      patients with chronic low back pain due to degenerative disk disease. Duration of
      the pain was between three and 24 months. Treatment consisted of nonsteroidal
      antiinflammatory drugs and/or analgesics, local corticosteroid injections and a
      plaster lumbar corset. Patients were evaluated at baseline, after ten days (under
      the same treatment), and at completion of the treatment. RESULTS: Results were
      reproducible for all four areas of the questionnaire (CCI > 0.75). Internal
      structural validity was satisfactory for the four areas (Cronbach alpha test =
      0.89 to 0.91). At baseline, the pain score on a visual analog scale was
      significantly correlated with the Dallas scores for daily activities,
      anxiety/depression and social interest (external structural validity). The daily
      activities, work/leisure and anxiety/depression scores were sensitive to change
      (P < 0.001, P < 0.001, and P = 0.003, respectively), whereas the social interest
      score was not (P = 0.11). CONCLUSION: The French version of the Dallas Pain
      Questionnaire is valid, reproducible, and sensitive to change in chronic low back
      pain patients.

PMID- 9540124
TI  - Medial meniscal cyst imitating a tumor, with compression of the saphenous nerve.
AB  - We report a case of large medial meniscal cyst responsible for symptomatic
      saphenous nerve compression in a 49-year-old male with a history of mild trauma
      to the affected knee. We are not aware of any similar cases in the literature.
      The lesion was delineated by ultrasonography and even more clearly by magnetic
      resonance imaging. At surgery, the saphenous nerve was seen to be displaced by
      the cyst. Cystectomy and partial meniscectomy were performed. The outcome was
      favorable.

PMID- 9540133
TI  - Beta-adrenergic blockade in chronic heart failure.
AB  - In summary, beta-blockade is currently the most promising "new" treatment
      undergoing Phase III testing in chronic heart failure. Multiple studies on the
      effects of these agents on LV function and chamber characteristics as well as
      limited survival data strongly suggest that these agents produce a beneficial
      effect on the natural history of heart failure. If this promise is borne out in
      the currently active or planned large-scale clinical trials, this form of therapy
      will emerge as the most valuable treatment available for chronic heart failure.

PMID- 9540134
TI  - Betablockers: old concept in a modern approach.
AB  - In summary, carvedilol lowers blood pressure effectively. There is a decrease in
      left ventricular mass. Carvedilol has a good metabolic profile and seems to
      improve insulin sensitivity. Through its effects on the endothelial function and
      its antioxidative properties carvedilol has positive effects on the
      atherosclerotic process. Carvedilol also decreases microalbuminuria. In several
      aspects carvedilol differs from the conventional beta-blocking drugs, and some of
      these effects are now being investigated in new studies.

PMID- 9540135
TI  - New hormonal blockade strategies in cardiovascular disease.
AB  - The circulation is controlled by overlapping haemodynamic, structural and
      neurohumoral mechanisms. Many hormonal vasoactive substances, mostly derived from
      endothelial cells, are also growth regulators. Although neurohormonal systems are
      involved in normal physiological compensatory responses they often become
      maladaptive in conditions such as congestive heart failure. The success of
      blocking the renin angiotensin system by angiotensin converting enzyme (ACE)
      inhibitors has led to efforts to block other hormonal systems. Neutral
      endopeptidase (NEP), the major enzymatic pathway for degradation of natriuretic
      peptides, has a similar catalytic site to ACE. This has led to compounds that
      simultaneously inhibit both enzymes. Such dual ACE/NEP inhibitors show promise in
      experimental hypertension and heart failure. Similar dual NEP/ECE (endothelin
      converting enzyme) inhibitors are becoming available. The hormone vasopressin has
      dual actions on the vasculature and the kidney via specific membrane receptors.
      Specific orally active vasopressin receptor antagonists have been developed and
      their therapeutic potential in hypertension, heart failure and oedematous states
      are being explored.

PMID- 9540132
TI  - Molecular genetics of congestive heart failure.
AB  - The manifestation of congestive heart failure occurs secondary to a great variety
      of cardiac or systemic disorders that share a temporal or permanent loss of
      cardiac function. In order to enhance our knowledge about the genetics of heart
      failure it is mandatory to analyse the aetiologic factors of these underlying
      disorders separately. Monogenic forms of congestive heart failure have initially
      been described by observant physicians in consecutive generations of affected
      families. Molecular genetic analyses of these families subsequently allowed us to
      localise and identify some of the genes that cause hypertrophic, dilative, or
      restrictive cardiomyopathies, congenital heart disease, as well as a number of
      inborn errors of metabolism. However, the great majority of patients develops
      heart failure as a final consequence of multifactorial conditions such as
      hypertension, cardiac hypertrophy, or coronary artery disease. Each of these
      conditions may be the product of a complex equation that includes environmental
      and genetic factors. Indeed, some of these factors may be harmful, others
      protective and for most it takes decades before a phenotype will be clinically
      detectable. Given this complex scenario it was not unexpected that early studies
      on candidate genes came up with partially controversial information. This review
      aims to summarize and to comment on the principal findings of this work.

PMID- 9540136
TI  - Carvedilol in the treatment of hypertension--a review of the clinical data base.
AB  - Carvedilol is a novel antihypertensive agent. It is a multiple-action
      neurohormonal antagonist with a beta-adrenoceptor blocking effect combined with a
      vasodilating action based on alpha1-adrenoceptor blockade. In addition,
      carvedilol exerts a number of well documented ancillary effects such as being a
      scavenger of free radicals. It also has an antiproliferative action on smooth
      muscle cells. This combination of effects opens up a number of interesting
      clinical perspectives. It is the purpose of this brief review to summarize some
      of the clinical studies that have been performed with carvedilol. Investigations
      in hypertensive patients will form the basis of this review, but special interest
      will also be devoted to other patient groups. In particular the therapeutic value
      of carvedilol will be discussed in patients with concomitant disorders such as
      atheromatosis, left ventricular hypertrophy, angina pectoris, myocardial
      infarction, congestive heart failure, arrhythmias, stroke, renal failure or
      diabetes. Finally, the usefulness of carvedilol in the treatment of elderly
      hypertensive patients will be reviewed. It is evident from the available
      scientific literature that carvedilol is an antihypertensive agent with a novel
      mode of action. It is effective in many of the subpopulations of patients alluded
      to above. It appears reasonable to assume that some of these therapeutic effects
      can be attributed to its ancillary properties.

PMID- 9540137
TI  - Scientific evidence and research in primary care.
AB  - The key areas of scientific research in general internal medicine are (1)
      prevention; (2) the natural history of common illnesses; (3) improving the
      outcomes and efficiency of the health care system and (4) orphan diseases.
      Disease prevention is at the top of the list because of the enormous role
      preventable causes play in morbidity and mortality, above all tobacco. Research
      in this field is difficult because it touches such questions as individual
      behaviour and personal choice. Research in the natural history of common
      illnesses is critical to informed patient decision making. Recent studies show
      that procedures thought to be safe bear a high percentage of complications, when
      viewed from the generalist's point of view: high incidence of strokes after
      elective coronary bypass surgery; higher mortality rates among patients having
      had pulmonary catheterization; high incidence of incontinence and impotence after
      transurethral resection of the prostate. A third area for research in primary
      care is how to improve outcome and efficiency through improvements in the health
      care delivery system. This field touches the problem of unnecessary surgical
      interventions and inappropriate prescription of antibiotics. Orphan diseases in
      this context are conditions no speciality wants to study, such as dementia and
      low back pain. The most important obstacle for research in the field of general
      internal medicine is funding. It is much easier to be funded for research in high
      profile conditions, like heart disease, cancer and AIDS. A second barrier to
      research relates to the role of special interest groups in influencing not only
      funding but also policy. Important examples were the pressure on consensus
      conference decisions on the role of spinal fusion surgery for low back pain and
      on the question whether women between 40 and 50 should have annual mammography.
      For generalist research to be fruitful it is of outmost importance to have an
      adequate intellectual infrastructure, i.e. support by epidemiologists,
      biostatisticians, economists and research methodologists.

PMID- 9540138
TI  - Clinical practice: between Aristotle and Cochrane.
AB  - Health and disease consist of amino acids and self image, cell membranes and
      human ideals, muscles and politics. Only to a limited extent can clinical
      practice be based on science. It can never be carried on in isolation from
      political, and cultural forces that influence patients' health behaviour.
      Evidence-based medicine is essential but not sufficient. A continuous
      relationship with patients is a conditio sine qua non for general practice. The
      general practitioner must be a master of pragmatic medicine. Rationality, the
      dominant modern trend, may be dangerous for patients and doctors: (1) advances in
      technology can give patients and doctors the illusion of mastering the universe;
      (2) patients complain of being treated like biomachines, without human touch.
      Another symptom of modernity is the decline of religion. But patients and doctors
      are by no means rational beings. God, destiny and hope are replaced by modern
      medico-scientific megalomania. Modern medicine is also strongly influenced by
      commercialization and invasion by bureaucrats. Instead of becoming a biomedical
      robot, the general practitioner must learn to value the Aristotelian concept of
      phronesis. It means practical wisdom and can only be gained by personal
      experience; a form of learning by doing. Good clinical practice cannot come from
      science alone, or from personal experience alone. It is an amalgam of scientia
      and phronesis.

PMID- 9540140
TI  - [Individualized drug therapy in geriatrics].
AB  - The process of modifying standard therapy to fit the needs of elderly patients
      calls upon physicians' interpersonal skills as well as their knowledge of normal
      and pathological aging and of clinical geronto-pharmacology. An individualized
      treatment plan is a synthesis of very subjective elements (such as the choice
      between painful curative treatment and less taxing but merely palliative
      treatment, or the establishment of treatment priorities) and more objective data
      such as renal function or drug characteristics. The reasons for individualizing
      therapy in the elderly patient, and how to achieve this, are reviewed.

PMID- 9540139
TI  - [Adjusting dosage of drugs in patients with kidney or liver failure].
AB  - Patients with renal or liver failure have a high risk of developing adverse
      effects of pharmacotherapy, since they are usually treated with many drugs and
      elimination of these drugs may be impaired. In this article, dose adjustment of
      the most important drugs used in these groups of patients is discussed. While
      clear guidelines for dose adjustment can be worked out for patients with renal
      failure this is more difficult for patients with liver failure since the
      metabolic capacity of the liver cannot be reliably quantified. Thus, despite dose
      adjustment, pharmacotherapy must be constantly monitored for adverse effects in
      these groups of patients.

PMID- 9540141
TI  - [Retrospective study of drug-induced agranulocytosis in hospitalized patients in
      Geneva and comparison with cases reported to IOCM].
AB  - In a retrospective study, 19 cases classified as idiosyncratic drug-induced
      agranulocytosis were found among 162 files of patients hospitalized in internal
      medicine clinics of the university hospital where this diagnosis had been coded.
      This would give an estimated incidence of 2.6 cases per million inhabitants per
      year for the Geneva area. In most cases several drugs were implicated in
      causation of the episodes. Suspected drugs were those commonly reported in the
      literature, but also some drugs which might already have been taken to treat
      infectious complications of agranulocytosis. A comparison of the Geneva cases
      with those notified to the Swiss Intercantonal Office for the Control of
      Medicines reveals a similar profile of involved drugs.

PMID- 9540142
TI  - [Self medication by the adolescent].
AB  - To evaluate the extent and motivations of self-medication, a survey was conducted
      among 376 adolescents aged 15 to 20 using both written questionnaires and face-to
      face interviews. 84% reported having taken some drug during the preceding 15
      days, 57% on their own initiative. The most frequently cited drugs were
      analgesics, vitamins, homeopathy and anti-inflammatory drugs. Psychotropics had
      been taken by 7% (as self-medication by 3%). Street drugs, mainly cannabis
      derivatives, had been taken by 18%. The most usual indications for self
      medication were headaches (42%), influenza-like syndromes (31%), school-related
      stress (21%), fatigue (19%) and mood concerns (15%). Most drugs were obtained
      from family reserves. A multivariate analysis showed self-medication to be
      associated with complaints regarding headaches, past drug dependency, concerns
      about illegal drugs or family interactions, recent respiratory illness, and
      diurnal somnolence. Self-medication increased with age. There was no relationship
      between self-medication and gender, citizenship, parental education level, or
      parental drug taking. Nor was self-medication related to knowledge about
      pharmaceuticals, assessed by specific questions. These results support the
      interpretation of self-medication mainly as a learned response to psychic/somatic
      ill-being. An optimal utility/risk ratio for self-prescribed drugs would require
      public health action and global involvement of practitioners.

PMID- 9540143
TI  - [Factors associated with refractory cancer pain].
AB  - Cancer pain can be effectively controlled in most patients by classical
      pharmacological treatment. We retrospectively studied the characteristics and
      factors associated with non responsive pain. Between 1989 and 1996, 1767 patients
      were referred to our pain center; 831 (47%) had cancer pain and from 787
      evaluable cases 118 (15%) experienced non-controlled pain whereas good pain
      control was achieved within a few days in 669 (85%) patients. Gender, age, cancer
      type, metastasis, initial pain intensity, nociceptive or neuropathic components
      and administration of adjuvant therapies were similar in both groups. On the
      other hand, diffuse pain, abdominal pain, terminal care, near death and doses of
      strong opioids were significantly different. Factors associated with therapeutic
      failure were conflicts, life and complications and breakthrough pain. In the
      presence of refractory cancer pain the factors predictive of therapeutic failure
      should be identified in order to optimize individual pain treatment.

PMID- 9540144
TI  - [Genetic and environmental effects on neuromodulation and the antinociceptive
      effect of dextromethorphan].
AB  - Administration of NMDA antagonists leads to attenuation or disappearance of some
      symptoms of central sensitization, such as secondary hyperalgesia. However, the
      side effects of NMDA antagonists to a large extent counterbalance the expected
      benefits, thus preventing wide or prolonged use. Dextromethorphan and its
      metabolite dextrophan, on the other hand, are established and safe drugs.
      Experimentally they both antagonize the NMDA receptor. This study evaluates the
      effects of dextromethorphan and its metabolite in pain models using electrical
      stimulation for testing the antinociceptive effect and capsaicin-induced
      hyperalgesia. Dextromethorphan shows clear antinociceptive as well as
      neuromodulary effects, both depending heavily on the cytochrome P450 2D6
      phenotype (CYP2D6).

PMID- 9540145
TI  - [Rapidly growing sternal nodule. Granuloma teleangiectaticum].

PMID- 9540146
TI  - Establishing the doctor-patient relationship: science, art, or competence?
AB  - Establishing and sustaining strong doctor-patient relationships is an important
      aim in clinical practice, since it is through these relationships that the
      effectiveness of our work as healers is mediated. In recent years, a research
      literature emerging from the application of social science to medicine is
      beginning to highlight certain specific physician behaviors, especially those
      involved in doctor-patient communication, as actions of considerable importance
      to both physicians and patients. Successful physicians will further understand
      that our patients and their families also have high expectations for additional
      behaviors of physicians, particularly those recognized in the popular culture as
      professional, respectful of patients' circumstances, and supportive of patients'
      efforts. To the extent that physicians make an explicit effort to understand and
      appreciate the "life-world" of patients, and even to modify medical
      recommendations in order to maximize the meaningfulness and goodness-of-fit of
      these recommendations, the "art" of medicine also becomes an essential part of
      routine clinical practice. In the final analysis, new science, art, and
      behavioral competence are all required for strengthening doctor-patient
      relationships.

PMID- 9540147
TI  - [From perception to symptom--from symptom to diagnosis. Somatoform disorders as a
      communication phenomenon between physician and patient].
AB  - Patients with somatoform disorders probably constitute the largest diagnostic
      group in daily medical practice. A major communication problem forms the core of
      somatoform disorders: patients report about complaints which their physicians do
      not understand; there is no sufficient biological reason for the patient's
      symptoms. This article discusses the multifactorial origin of somatoform
      disorders, consisting of minimal physiological changes, the perception of bodily
      sensations, and their interpretation as symptoms (non-normal perceptions), as
      well as ensuing emotional and behavioral consequences. Concerning the
      communication problem, it is important to realize that patients normally present
      symptoms, whereas the underlying bodily perceptions and the explanatory models
      are rarely communicated to the physician. On the physician's side, symptoms
      presented by patients are subjected to his or her explanatory concepts
      translating symptoms into indicators of certain diseases. Thus, the information
      introduced into physician-patient communication by the patient has usually passed
      several cognitive circuits within the patient or between the patients and other
      significant conversation partners thus shaping its specific components. It is
      recommended that physicians try to trace back their patients' symptoms to bodily
      sensations and explanatory models in order to base their diagnostic and
      therapeutic reasoning on the same kind of information. Empirical evidence is
      presented to support the inter-dependence of the components of the model, on both
      the patient's and the physician's side. Therapeutic interventions based upon the
      model are presented.

PMID- 9540148
TI  - [Objective diagnosis, relational diagnosis--science or art?].
AB  - This paper describes the dilemma the psychotherapist faces when dealing with the
      psychosomatic disorders that are referred to him by the primary care physician.
      Psychosocial and psychosomatic evaluation and treatment standards are based on
      relational and contextual dimensions, in order to assign comprehensive and
      meaningful perspectives to previously disconnected symptoms. On the other hand,
      quality management and cost-benefit criteria require the use of objective
      diagnosis, decisional trees and treatment guidelines. The author proposes an
      ethical compromise and a doctor-patient negotiated partnership as a solution to
      the dilemma.

PMID- 9540149
TI  - [Ultrasensitive TSH screening for detection of thyroid gland dysfunctions in
      women of a medical ambulatory care patient group].
AB  - This aim of the study was to identify the prevalence of unsuspected thyroid
      dysfunction in a female population attending a medical primary care unit (case
      finding study). A TSH assay of the third generation was used as a screening test.
      The overall prevalence of unsuspected thyroid dysfunction in 1061 female patients
      was 2.5% (0.5% overt hyperthyroidism, 0.3% overt hypothyroidism, 0.5% subclinical
      hyperthyroidism, and 1.2% subclinical hypothyroidism). The prevalence of thyroid
      disease is clearly age dependent with 4.3% over the age of 40 and 5.9% for 50-60
      year-olds. The ratio for females below 40 and over 40 was 10.75 (Odds ratio, p <
      0.0001). We conclude from our study and from the literature that TSH screening as
      a case-finding strategy is indicated, and also seems cost-effective, in women
      over 40 years of age.

PMID- 9540150
TI  - [Differences in the relative incidence of adverse drug reactions in relation to
      age? An evaluation of the spontaneous reporting system of SANZ (Swiss Drug
      Monitoring Center)].
AB  - The risk of presenting adverse drug reactions (ADR) is greater for elderly
      patients. Chronological age is not an independent risk factor for ADRs, but age
      dependent factors such as polymedication, multiple diseases and changes in
      pharmacokinetics and pharmacodynamics seem to be responsible for the risk of
      developing more adverse drug reactions. We analyzed the ADRs spontaneously
      reported to the Swiss Drug Monitoring Centre (SANZ) between 1981 and 1995. Age
      specific relative incidences of the reported ADRs affecting different organ
      systems were calculated. For elderly patients we found a decrease in the relative
      incidence of dermatological ADRs and an increase in neuropsychic and
      hematological ADRs. The incidence of serious ADRs increased by 8.7% in older
      patients (> 70 years). The results of this analysis of spontaneous reports were
      inconsistent with results from epidemiological studies. The possibility and
      reasons for under-reporting ADRs occurring in elderly patients are discussed.

PMID- 9540151
TI  - [Comparison of propacetamol and morphine in postoperative analgesia].
AB  - To compare the analgesic efficacy and tolerance of propacetamol and morphine, 80
      patients in good clinical condition were included in a prospective, parallel,
      randomized double blind trial after elective surgery expected to elicit light to
      moderate postoperative pain. At the end of general anesthesia, 40 patients
      received 30 mg/kg propacetamol and 40 0.2 mg/kg morphine, as a 15-min intravenous
      infusion. The groups were similar for age, weight and duration of anesthesia.
      Supplemental analgesia had to be given in 7 cases from the propacetamol group vs.
      2 cases from the morphine group. The postoperative pain, evaluated 7 times during
      4 h from the end of infusion with a visual analog scale, revealed a modest
      advantage for morphine at 0.5 and 4 h (p = 0.05). The respiratory rate was
      slightly lower after morphine (p = 0.02). No significant differences were
      observed in blood oxygen saturation, blood pressure, heart rate, body temperature
      and vigilance evaluated by the trailmaking test. Nausea was present in 4 cases
      under propacetamol and 3 under morphine, and pruritus in 2 and 7 cases,
      respectively. In conclusion, propacetamol may represent an alternative to
      morphine for pain prevention after mildly to moderately painful surgery in
      situations where the use of opioids is unsuitable.

PMID- 9540152
TI  - [Pulmonary tuberculosis with resistance to 4 antitubercular drugs].
AB  - A 32-year-old immigrant from Pakistan was admitted to our hospital with cavernous
      pulmonary tuberculosis. He gave a history of several 1 to 2-months courses of
      antimycobacterial treatment administered earlier in Pakistan. We initiated
      combined therapy including isoniazid, rifampin, pyrazinamide, and ethambutol.
      Subsequently, results of susceptibility testing from M. tuberculosis-complex
      strains isolated before the onset of treatment documented the presence of
      resistance against both isoniazid and rifampin which may have been primary or
      acquired drug resistances. During the course of treatment, two additional
      resistances to pyrazinamide and ethambutol developed which were probably due to
      the initial therapy with only two active antimycobacterial agents. The emergence
      of multidrug-resistant strains of M. tuberculosis complex is a world-wide
      problem. Our case indicates that multiresistance must be considered in every
      patient presenting with tuberculosis. If there is a strong suspicion of multidrug
      resistant tuberculosis, initial treatment with a combination of 5-6
      antimycobacterial agents seems advisable until the results of susceptibility
      testing become available.

PMID- 9540153
TI  - [Antibiotic utilization in a university geriatric hospital and drug formularies].
AB  - Inappropriate use of antibiotics needlessly increases drug expenditures, enhances
      the emergence of antimicrobial resistance in hospitals and heightens the risk of
      toxicity, especially in elderly patients. This population is very sensitive to
      inappropriate drug treatment because of pharmacological and pharmacokinetic
      changes, reduced homeostatic functional reserve, multiple underlying diseases
      (e.g. renal failure) and polypharmacy (leading to drug interactions and side
      effects). To assess antibiotic prescription in a geriatric university hospital
      with a restrictive drug formulary, we analyzed data extracted from the Drug
      Kardex (a standardized synthesis of all prescribed medicines) during 4 cross
      sectional drug utilization studies, carried out in 1996 on all hospitalized
      patients. RESULTS: 1138 patients' Kardex have been analyzed. 20% of these
      patients received one or more antibiotic treatments. In total 268 antibiotic
      treatments (AB) were prescribed, 84 in March, 44 in June, 71 in September and 66
      in December. 21 different AB were used, the five most frequently prescribed AB
      being amoxycillin-clavulanic acid, ceftriaxone, ciprofloxacin, metronidazole, co
      trimoxazole and representing 69% of all AB. Most of the AB were given in an oral
      form (63%) and in one standard dose. Dose adjustments in these very old patients
      with a high percentage of renal failure were apparently rarely done. The choice
      of rather broad spectrum AB may be due to the fact that obtaining an appropriate
      bacteriological culture from elderly patients with respiratory tract infections
      is difficult, but was also due to a lack of diagnostic subcategorization of the
      infection. Undesirable effects of the restrictive drug formulary were also noted:
      large utilization of ciprofloxacine (only fluoroquinolone on the hospital's drug
      list) for urinary tract infections instead of other more appropriate antibiotics.
      CONCLUSION: It is important to individualize antibiotic drug therapy with respect
      to underlying diseases, site of infection and antibiotic sensitivity patterns,
      especially in elderly patients. Restrictive hospital drug formularies are not
      sufficient to assure rational drug use, but should be associated with broader
      educative measures.

PMID- 9540154
TI  - [Hypotensive effect of an inhibitor of cholesterol synthesis (fluvastatin). A
      pilot study].
AB  - To investigate whether fluvastatin lowers cholesterol and blood pressure in
      hypertensives and hypercholesterolemic patients, 23 patients followed by their
      medical practitioner received 40 mg fluvastatin once a day for 12 weeks. Arterial
      blood pressure was measured by continuous ambulatory monitoring. Total mean
      cholesterol (mmol/l) was lowered from 7.98 +/- 1.21 to 6.25 +/- 0.88 and the
      atherogenic index from 7.26 +/- 2.11 to 5.49 +/- 1.35. Mean arterial systolic and
      diastolic blood pressure (mm Hg) was reduced from 144.8 +/- 13.7 to 138.6 +/- 18
      and from 97.3 +/- 9.1 to 92 +/- 10.8. In responders (n = 12), blood pressure
      decreased from 142.6 +/- 11 to 126.4 +/- 11.1 and from 99.6 +/- 7.1 to 88.3 +/-
      6.5. In conclusion, fluvastatin prescribed in a dose of 40 mg/day for 3 months to
      23 hypertensives and hypercholesterolemic patients lowers the cholesterol level
      and lowers blood pressure. Lowering of blood pressure is independent of lowering
      of cholesterol.

PMID- 9540156
TI  - Immunopathology of apoptosis--introduction and overview.

PMID- 9540155
TI  - [Penetrating atherosclerotic ulcer of the aorta].

PMID- 9540157
TI  - Receptors and ligands that mediate activation-induced death of T cells.

PMID- 9540158
TI  - Clinical effects of mutations to CD95 (Fas): relevance to autoimmunity?

PMID- 9540160
TI  - Lymphocyte granule-mediated cell death.

PMID- 9540159
TI  - Can expression of CD95 (Fas/APO-1) ligand on grafts or tumor cells prevent their
      rejection?

PMID- 9540161
TI  - Apoptosis by p53: mechanisms, regulation, and clinical implications.

PMID- 9540162
TI  - Fatigue and cachexia in cancer patients.

PMID- 9540163
TI  - News from MASCC Subcommittees. Infectious subcommittee.

PMID- 9540164
TI  - Palliative care in India.
AB  - While India has a long tradition of home-based spiritual and religious care of
      the dying, there has been no contemporary palliative care until relatively
      recently. The existing and planned palliative care services in India are
      presented, and future perspectives and the opportunities for training for both
      professionals and lay volunteers are discussed.

PMID- 9540165
TI  - Parenteral versus enteral nutrition in cancer patients: indications and practice.
AB  - Prospective randomly controlled trials have failed to demonstrate the clinical
      efficacy of providing nutritional support to most cancer patients in terms of
      morbidity, mortality, and duration of hospitalization. Serious shortcomings in
      study design have limited the possibility of drawing definitive conclusions from
      the data. Thus, nutritional intervention needs to be seen as a method of support,
      with the aim of maintaining nutritional and functional status during the stress
      of the oncology treatment to prevent or attenuate cachexia. There is no disease
      during which the patient benefits from prolonged wasting. Pretreatment weight
      loss is quoted as a major indicator of poor survival and response to therapy of
      cancer patients. As a consequence, an early and serial assessment of nutritional
      status, perhaps followed by an immediate intervention with nutritional support is
      strongly recommended. There are other specific reasons for using the gut rather
      than the intravenous route for nutrient administration besides the often reported
      disadvantage of significant cost. Local intestinal stimulation prevents the
      mucosal atrophy and bacterial translocation that can be triggered by several
      precipitating factors, as frequently seen in oncologic patients. These include
      endotoxin, radiation therapy, cytotoxic and immunosuppressive drugs, cytokines,
      bowel and biliary obstruction, broad-spectrum antibiotics, and the tumour itself,
      as well as parenteral nutrition (PN). As the enteral route of nutritional support
      has been found to be as good as or preferable to PN in terms of maintenance of
      nutritional status or immune function, prevention of bacterial translocation,
      maintenance of normal gut flora, transit and histology, and prevention of
      hypercatabolic responses to stressful events, it is always preferable in terms of
      physiological response, local and systemic competence, quality of life and cost,
      and should be the method of choice for the nutritional support of cancer
      patients. Although retrospective studies of PN suggest a benefit for patients
      with cancer who are undergoing surgery, radiation, or chemotherapy, carefully
      designed, prospective studies report less conclusive findings. The failure of
      conventional PN to improve clinical outcomes in patients with cancer may be
      related to the fact that standard formulations do not address or reverse
      abnormalities of intermediate metabolism that result in cancer cachexia.
      Supplemental substances have been proposed in an attempt to improve the efficacy
      of PN, including insulin, growth hormone and branched chain amino acids. The
      difficult task is to identify those patients who are at risk for malnutrition and
      at the same time identify the subset of patients who will benefit clinically from
      parenteral nutritional repletion. Severe malnutrition in patients requiring
      surgery, bone marrow transplantation in patients unable to tolerate enteral
      supplementation and postoperative complications necessitating nutritional support
      are specific indications. Routine use of PN should be discouraged.

PMID- 9540166
TI  - Measuring fatigue in patients with cancer.
AB  - Our current state of knowledge of the fatigue experienced by patients with cancer
      is limited, and further development is hampered by the definitions of fatigue,
      which remain numerous, inconsistent, and varied according to the discipline of
      the author and the nature of the research. It is fairly well established within
      the healthcare literature that it is multidimensional in nature. This has
      implications for the reliable and valid assessment of this phenomenon. There are
      a number of instruments currently available with which to measure cancer-related
      fatigue. These include instruments developed for use initially with healthy
      populations, such as airmen and workers engaged in manual and clerical work.
      However, cancer-specific fatigue assessment instruments are now available, and
      are preferable to those instruments developed without reference to this patient
      group. Fatigue is often found as a single item or scale in self-report measures
      of symptoms, mood and functional status reflecting the effect of fatigue and the
      interaction of fatigue with other symptoms or concepts related to quality of
      life. Factors to be considered in selecting a measure of fatigue for research
      will be outlined, and recommendations for the future development and validation
      of useful and scientifically credible measures of fatigue made.

PMID- 9540167
TI  - Fatigue, depression and quality of life in cancer patients: how are they related?
AB  - In a study concerning a group of cancer patients undergoing radiotherapy three
      research questions were addressed. (1) Is fatigue a valid criterion for
      depression in these somatically ill patients? (2) What is the 'cause-and-effect'
      relation between fatigue and depression? (3) To what extent are fatigue and
      depression related to patients' quality of life. A heterogeneous sample of cancer
      patients (n = 250) were interviewed before treatment, 2 weeks after treatment and
      9 months later. Fatigue was measured using the MFI, a self-report instrument
      covering five dimensions of fatigue. Depression was assessed with the non-somatic
      items of the CES-D. Quality of life had to be indicated on a Cantrill ladder.
      Fatigue and depression do not follow the same course over time. Just after
      radiotherapy, fatigue had either increased or remained stable, depending on the
      dimension under consideration. Depression, in contrast, decreased. Nine months
      later fatigue had decreased, whereas levels of depression remained stable.
      Concurrent relations between fatigue and depression were mostly moderate. There
      was no strong evidence for a cause-and-effect relationship between depression and
      fatigue. Depression showed highest concurrent relationships with quality of life,
      especially before treatment. Prospectively, depression and the dimension of
      physical fatigue were the main predictors for quality of life. Fatigue is not a
      valid criterion for depression in these patients. Nor is there a strong cause-and
      effect relationship. Both depression and physical fatigue are relevant to
      patients' quality of life.

PMID- 9540169
TI  - Supportive care and euthanasia--an ethical dilemma?

PMID- 9540168
TI  - Pharmacological treatment of cachexia: any progress?
AB  - In view of the renewed interest in pharmacological treatment of anorexia-cachexia
      in cancer patients over the past 3 years, both the established drugs used in its
      treatment and the emerging new drugs still being tested for it are reviewed.
      Results of trials that have already been evaluated are reported, and possible
      areas for further research are indicated.

PMID- 9540170
TI  - The code of conduct of the volunteer.
AB  - Voluntary service has experienced a considerable expansion and a substantial
      change over the last two decades. The role of the volunteer has gradually come to
      interact with activities undertaken by other professionals, but without
      interfering. Since the role of the volunteer naturally involves autonomy and
      discretion on his/her behalf, the associations concerned increasingly feel the
      need to refer to standards defining a voluntary service ethic. Within a refresher
      course with a set number of places for non-profit-making organisations, which was
      arranged by the Italian League against Cancer, Milan, a consensus conference for
      the ratification of a code of conduct on voluntary service was held. The aim was
      to reach a consensus together with others who work in an "organised" manner every
      day, on ethical concepts that should inspire voluntary service: the common good,
      mutual respect, freedom of choice, a non-profit-oriented vision. After exhaustive
      discussions by three panels, the text of a code of conduct unanimously approved
      was elaborated. All concerned with this code tried to avoid giving it a
      "sanitary" imprint. It is in fact our opinion that whatever the area covered by
      voluntary service, its aim and its final objective is to ensure the wellbeing of
      mankind and his environment.

PMID- 9540171
TI  - Aerobic and anaerobic infection associated with malignancy.
AB  - The goal of this work was to study the microbiology and clinical characteristics
      of patients with infections associated with malignancy treated over a period of
      17 years. A total of 668 specimens were obtained from 605 patients. The
      malignancies include 224 hematological malignancies and 381 nonhematogenic
      malignancies. Anaerobic bacteria only were isolated in 201 (30%) specimens,
      aerobic bacteria in 226 (34%), mixed aerobic-anaerobic bacteria in 231 (35%) and
      Candida spp. in 10 (1%). A total of 683 anaerobic (1.0 isolates per specimens)
      and 592 aerobic or facultative (0.9 per specimen) organisms were recovered. The
      predominant anaerobic bacteria included Bacteroides fragilis group isolates
      (181), Peptostreptococcus spp. (166), Prevotella spp. (106), Clostridium spp.
      (70), and Fusobacterium spp. (43). The predominant aerobic bacteria included
      Escherichia coli (133), Staphylococcus aureus (100), Klebsiella pneumoniae (48),
      and Pseudomonas aeroginosa (45). The type of infections included abscesses (221),
      bacteremia (198), wounds (175), including 61 cellulitis, 24 post-surgical wounds
      and 23 decubitus ulcers), peritonitis (48), empyema (12), cholecystitis (6) and
      thrombophlebitis (5). S. aureus and Peptostreptococcus spp. were isolated from
      all sites. However, organisms of the oropharyngeal flora (Prevotella and
      Fusobacterium spp.) predominated in local infections and bacteremia that
      originated from this site (head and neck wounds and abscesses and pulmonary
      infections), and organisms of the gastrointestinal tract flora predominated in
      infections that originated from this site (peritonitis, abdominal abscesses and
      decubitus ulcers). This retrospective study demonstrates polymicrobial features
      of many infections associated with malignancies.

PMID- 9540172
TI  - Assessment of the emetogenic potential of intrathecal chemotherapy and response
      to prophylactic treatment with ondansetron.
AB  - The purpose of this study was to document the emetogenic potential of intrathecal
      chemotherapy (IC) in children and to evaluate the efficacy of ondansetron in
      reducing nausea and vomiting with this chemotherapy treatment. Patients less than
      18 years of age with acute lymphoblastic leukemia were eligible to participate in
      a survey project measuring the emetogenic potential of various chemotherapy
      treatments. Patients surveyed for 1 or more IC treatments were included in this
      report. The IC consisted of methotrexate, hydrocortisone and cytarabine, dosed
      according to patient age. A nausea/vomiting survey instrument was completed by
      each patient and/or parent following IC treatment. The instrument rated nausea,
      vomiting and daily activity interference (DAI) on a 4-point scale of 0 = none, 1
      = mild, 2 = moderate and 3 = severe, and collected data on the number of vomiting
      and/or retching episodes in addition to the child's appetite following the
      chemotherapy treatment. When ondansetron was employed, it was administered in an
      i.v. infusion at a dose of 0.15 mg/kg before and after chemotherapy or as an oral
      dose of 4 mg or 8 mg before chemotherapy. Courses of IC without antiemetics were
      analyzed to determine the emetogenic potential of IC. For patients receiving IC
      both with and without ondansetron, courses were compared with each patient used
      as their own control to determine the influence of ondansetron upon survey
      responses. Statistical analysis consisted of nonparametric Friedman 2-way ANOVA
      for ordinal variables and a paired t-test for continuous variables. The binomial
      test was employed to analyze for differences between ondansetron and no
      antiemetic in the number of patients with complete control of both nausea and
      vomiting or vomiting alone. A total of 63 children with a mean age of 7.6 +/- 4.2
      years were each studied on one or more occasions. Thirty-seven children were
      surveyed for 87 IC treatments without antiemetics (group I), and 17 children from
      this group were surveyed for 48 IC courses with i.v. ondansetron (group IA). An
      additional 18 children were subsequently surveyed for 39 IC courses with i.v.
      ondansetron (group II). Fifteen patients (7 of whom were members of group I) were
      surveyed following 33 IC courses with oral ondansetron (group III). The survey
      scores for group I patients were: nausea severity 1.3 +/- 1.1, vomiting severity
      1.2 +/- 1.1, DAI 1.2 +/- 1.0 and mean number of emetic episodes 4.7 +/- 8.4. The
      mean appetite score was 1.5 +/- 1.1. For patients in group IA, nausea severity
      (0.8 +/- 0.9), vomiting severity (0.5 +/- 0.8), DAI (0.7 +/- 0.8), and the number
      of emetic episodes (1.4 +/- 2.8) were all significantly lower than with prior IC
      treatments without ondansetron. For complete protection, children receiving i.v.
      ondansetron had greater complete protection rates from both nausea and vomiting
      or vomiting alone than did patients receiving no antiemetic. Survey responses
      were also lower for patients receiving oral ondansetron, but insufficient control
      data did not allow for statistical analysis. IC results in mild to moderate
      nausea and vomiting in children. The emetogenic potential of IC is significantly
      reduced by i.v. ondansetron.

PMID- 9540173
TI  - Different doses of pamidronate in patients with painful osteolytic bone
      metastases.
AB  - Cancer patients with painful osteolytic bone metastases who had failed initial
      treatment with hormones and/or chemotherapy were each randomized to receive one
      of three pamidronate doses as outpatients: 45, 60, 90 mg given every 3 weeks for
      12 weeks. Seventy patients were enrolled in this study, for a total of 265
      infusions. There were 64 patients who completed 12 weeks of therapy. Forty-eight
      patients took nonsteroidal antinflammatory drugs, while 22 patients received
      morphine before pamidronate treatment. A reduction in bone pain and mobility
      scores was observed in all three different dose groups: in 11 of 23 patients
      (47%) at 45 mg; in 12 of 24 patients (50%) at 60 mg; and in 16 of 23 patients
      (69%) at 90 mg. However, while for patients receiving pamidronate at 90 mg median
      changes in pain and mobility were statistically significant at the 6th week, for
      patients receiving 45 mg they were not significant until the 12th week and for
      patients receiving 60 mg, until the 9th week. In weeks 0-6, the daily consumption
      of analgesics was reduced in 3 patients in the 45-mg arm, in 4 patients in the 60
      mg arm, and in 7 patients in the 90-mg arm. In weeks 7-12, the daily consumption
      of analgesics was reduced in 8 patients receiving 45 mg, in 8 patients receiving
      60 mg, and in 7 patients receiving 90 mg. No significant toxicity was recorded.
      In 2 patients (45 and 90 mg) fever (> 38 degrees C) and myalgia were observed
      after the first administration. In conclusion, our results seem to confirm the
      utility of higher doses of pamidronate in patients with painful bone metastases,
      because of the faster symptom relief achieved.

PMID- 9540174
TI  - Use of mesna to prevent ifosfamide-induced urotoxicity.
AB  - The purpose of this study was to make evidence-based recommendations regarding
      the mode, dosage and schedule of delivery of concomitant mesna (sodium-2
      mercaptoethanesulfonate) to protect against ifosfamide-induced uroepithelial
      toxicity. A critical review of the literature from 1966 to 1996 was undertaken on
      mesna administration via the intravenous, oral, or combined modality routes.
      Outcome measures of urinary symptoms and macrohematuria were emphasized, since
      these endpoints of urotoxicity are most clinically relevant. The quality of
      evidence obtained from published clinical research was evaluated based on
      guidelines developed by the Canadian Task Force on the Periodic Health
      Examination. Recommendations are now made according to the strength of available
      evidence on the proper usage of mesna as a protective agent against ifosfamide
      induced urotoxicity. There is good evidence that the use of mesna significantly
      reduces urinary symptoms of dysuria and frequency, as well as the incidences of
      macrohematuria and microhematuria, when administered concurrently with any dosage
      of ifosfamide regardless of tumor site. Mesna, given intravenously or orally, is
      superior to standard prophylaxis with vigorous hydration and alkalinization of
      urine. A commonly used schedule of intravenous mesna involves a dose equal to 60%
      of the total ifosfamide dose, divided into three aliquots and administered at 0
      h, 4 h and 8 h after ifosfamide. Combined oral and intravenous mesna delivered in
      some tested schedules is equivalent to intravenous mesna alone, but the optimal
      schedule and dosage of combined formulation have not yet been established. There
      is fair indirect but no direct evidence that oral mesna alone is equivalent to
      intravenous mesna or combined modality use. Further research issues, such as
      patient compliance with oral mesna and other routes of mesna delivery, are
      discussed. Ongoing study in the appropriate use of mesna is needed to maximize
      its value as a uroprotective agent in the clinical setting.

PMID- 9540175
TI  - Radiochemotherapy with amifostine cytoprotection for head and neck cancer.
AB  - A randomized study was conducted to evaluate the protective activity of
      amifostine (A) against the dose-limiting toxicities of radiochemotherapy (RCT).
      Patients with head and neck cancer received radiotherapy (2 Gy/day 5 days a week
      up to 60 Gy) with carboplatin 70 mg/m2 on days 1-5 and 21-25 inclusive. Patients
      either received RCT alone (n = 14) or RCT + A at a dose of 500 mg prior to
      treatment with carboplatin (n = 25). There was a significant reduction in the
      incidence of grade 3/4 mucositis (P < 0.0001), acute grade 2 xerostomia (P <
      0.0001) and grade 3/4 thrombocytopenia (P = 0.012) in these patients who received
      A. The incidence of grade 2 late xerostomia at 12 months is 16.7% and the
      incidence of loss of taste is 0% in patients treated with A, as opposed to 54.5%
      and 63.6% in patients who received RCT alone. There were 18 (72%) complete
      responses (CR) and 6 (24%) partial responses (PR) in patients who received A,
      compared with 6 (43%) CR and 6 PR (43%) in patients treated with RCT alone. The
      disease-free survival at 12 months is 85.7% in the RCT + A arm and 78.6% in the
      RCT alone arm. The use of amifostine reduces the incidence and severity of acute
      and late toxicities associated with RCT whilst preserving antitumour activity.

PMID- 9540177
TI  - [Diagnosis of urethral stricture--what is necessary?].
AB  - For therapy of strictures of the urethra several procedures are available. The
      choice of the adequate strategy requires a rational diagnostic, answering
      questions about localisation, length, shape and functional effect of the
      stricture. The most important method is the miction-cyst-urethrography (MCU).
      Statements about the dimensions of scarred alterations in the corpus spongiosum
      urethrae are to receive from urethral ultrasonic. In addition you can perform the
      retrograde urethrography. The functional effects of the urethral stricture should
      be investigated by uroflowmetry and examinations of the upper urinary tract
      (ultrasonic/urography).

PMID- 9540176
TI  - [Anatomy and blood supply of the penis and urethra].
AB  - The exact knowledge of the topographic anatomy of the urethra as well as the
      macro- and microcirculation of the penis [6] are the basics of reconstructive
      urethral surgery. Adherence to the fundamentals and principles of tissue transfer
      [5] are necessary to fascilitate conditions for successful treatment of the
      various disorders of the male urethra. Mutural description of the anatomy of the
      male urethra in conjunction with external male genitals is necessary because of
      developmental similarities as well as the close anatomical relationship. The
      arterial and venous blood supply of the urethra and the penis have to be taken
      into account if vascularized flaps from the penile skin or the prepuce are used
      in urethral reconstruction. The dual arterial and venous vascularity of the
      genital skin is of fundamental importance to a successful outcome of the
      operative treatment. The purpose of this article is, to summarize the relevant
      anatomical knowledge of reconstructive urethral surgery.

PMID- 9540178
TI  - [General principles in treatment of urethral strictures].
AB  - This manuscript outlines the important points in the evaluation and treatment of
      urethral stricture disease. The algorithms described within are not presented as
      strict guidelines but rather are intended to give a logical thought progression
      which incorporates the basic principles of urethral reconstruction. It is
      important to determine the therapeutic goal before applying these principles.
      There are basically two arms of consideration, the first is to attempt to cure
      the patient of urethral stricture disease and the second is to simply manage the
      patient's urethral stricture disease without intent of cure. Applying the current
      knowledge of anatomy with modern tissue transfer techniques will achieve a highly
      successful, single stage reconstruction in most patients. Although approaching
      urethral stricture disease with the intent to cure is preferred, management may
      not be unreasonable in certain cases. Some patients have entensive co-morbidities
      or may prefer a trial of conservative measures before definitive treatment is
      undertaken. If the goal established is urethral reconstruction, the gold standard
      is to perform a single stage procedure that is highly successful and durable.
      Excision of the urethral stricture with primary anastomosis (EPA) represents this
      gold standard. However, ist application is limited by stricture location or
      length. An accurate evaluation of the stricture location, length, and associated
      spongiofibrosis is mandatory in forming viable options for repair. By exploiting
      the advantages of differing techniques, the proper course of action can be chosen
      which generally will solve even the most complex problem in one stage. The
      reconstructive surgeon come to the operative suite armed with the full knowledge
      and understanding of the principals and techniques which will result in a
      favorable outcome. It is not uncommon for intra-operative findings to guide the
      decision for the best alternative for urethral reconstruction. We also offer some
      helpful hints regarding positioning, sutures, exposure, and retractors.

PMID- 9540179
TI  - [Internal urethrotomy].
AB  - Urethral dilatation and urethrotomy can be effective treatments of the stricture
      disease in selected patients when the spongy tissue is not severely damaged. In
      the few reports comparing urethrotomy and dilatation, results are not
      significantly different. A long term followup is mandatory in assessing the
      outcome of treatment of urethral strictures. Characteristics of the stricture as
      location, length, caliber, number, and previous failed treatments allow to select
      the best therapeutical option. After the failure of the first instrumentation,
      repeated procedures are not curative.

PMID- 9540180
TI  - [Bulbo-bulbar and bulbo-prostatic anastomosis of the urethra].
AB  - Strictures of the bulbous and membranous urethra up to 2.5 cm in length and after
      visual urethrotomy should be managed with an one-stage perineal anastomotic
      repair. With description of the surgical techniques the results of 41 patients,
      treated between 1977 and 1996, are presented. 28 patients had bulbomembraneous
      strictures as result from urethral disruption at the time of pelvic fracture. In
      13 cases with bulbar strictures, 11 had been caused iatrogenously and 2 by
      infection. A successful outcome was achieved in over 90% (37 patients),
      equivalent to a maximum uroflow over 15 ml/s, an empty bladder after voiding and
      a radiographic wide anastomosis. Only 4 patients (9.8%) after surgery required an
      urethrotomy; two of them are dilated frequently.

PMID- 9540181
TI  - [Reconstruction of the posterior urethra].
AB  - The posterior prostatomembranous urethral stricture or distraction defect has
      historically been the most formidable challenge of stricture surgery. This
      uncommon lesion occurs most often as the sequelae of pelvic fracture injuries, or
      straddle trauma, and is associated with serious urethral disruption and
      separation--an injury that is often complicated by inappropriate initial
      management using substitution skin flap techniques with the development of
      recurrent stenosis, irreversible impotence, and occasional incontinence.
      Management by endoscopic techniques may be possible in patients with short
      strictures or in those after prostatectomy, but they rarely play a role in
      resolving the complex obliterated urethra with a significant defect [1].
      Resolution of post-traumatic posterior urethral distraction defects and other
      posterior urethral pathologic conditions has dramatically improved over the past
      two decades despite an inaccessible subpublic location involving exposed
      sphincter-active and erectile neurovascular anatomy. The contemporary, perineal,
      one-stage bulboprostatic anastomotic operation as popularized by Turner-Warwick
      [20] with selective scar excision is a versatile procedure with a high patent
      lumen success. Patients undergoing anastomotic urethroplasty have a substained
      patent urethral lumen success rate approaching 100% versus those who have
      undergone urethral skin flap or patch repair, where the restricture rate in 5 and
      10 years increases twofold to threefold [1, 20]. A patent urethra after an
      anastomotic urethroplasty at 6 months is free from further recurrent stricture
      and gives credence to Mr. Turner-Warwick's admonition that "urethra is the best
      substitute for urethra".

PMID- 9540182
TI  - [Therapy of urethral stricture using free transplants].
AB  - Single stage urethroplasty with an onlay patch graft of penile skin or buccal
      mucosa is an effective treatment for patients with complex anterior urethral
      stricture disease. Using buccal mucosa, operative time is substantially reduced
      by using a two-team approach in which one team harvests the graft from the mouth
      while a perineal team simultaneously exposes and calibrates the stricture.
      Excellent results can be expected using grafts urethral substitution in men with
      refractory bulbar strictures. Focal areas of severe stenosis may be excised from
      the graft bed. For patients with long or dense stricture, grafts may easily be
      combined with other tissue transfer techniques.

PMID- 9540183
TI  - [Two-stage urethra-plasty].
AB  - Between 1977 and 1996 we treated 176 patients suffering from complicated urethral
      strictures with the mesh-graft urethroplasty. This operation technique has
      replaced the Bengt-Johanson-Operation which had been used frequently until that
      date. The Cecil-Operation has been totally abandoned, because in our opinion the
      usage of scrotal skin in urethral reconstruction is obsolete today. The mesh
      graft technique is based on the free transfer of meshed prepuce (full-thickness
      skin or split-thickness skin) in a two stage procedure. In 37 patients the inner
      layer of the prepuce was used, in 63 patients we only used split-thickness skin
      grafts and in 76 patients we applied a combination of both, the inner layer of
      the prepuce in addition to a split-thickness skin graft. After complete healing
      of the graft (first stage) the formation of the neourethra follows as the second
      stage procedure. The mesh graft procedure can be used to treat all kinds of
      strictures independent of the etiology or localisation. Hair growth, diverticula
      development and stone formation that are observed frequently as complications
      with scrotal skin substitutes can be avoided. Due to these advantages encouraging
      long term results could be obtained with the mesh graft urethroplasty. In 162
      patients (92%) with a minimum follow-up of 7 years we achieved a successful
      result of the operations, a significant improvement could be obtained in 7
      patients (4%). Unfortunately in further 7 cases (4%) the operation method
      ultimately failed. In particular in patients with complicated and severe
      strictures after numerous unsuccessful prior reconstructive attempts, extensive
      long strictures and strictures in paraplegic patients, mesh graft urethroplasty
      has been shown to be a safe and reliable treatment option.

PMID- 9540184
TI  - [Stents in therapy of urethral strictures].
AB  - The human urethra seems remarkably tolerant of foreign material within its lumen.
      Providing that a stricture has been adequately cut by means of urethrotomy, or
      dilated with bougies, the majority of urethras will tolerate both permanent and
      temporary stents with few problems. Temporary stents have the obvious advantage
      over permanent stents that no foreign material is left in the urethra but before
      these can be recommended it is essential that more clinical experience is gained
      and that long term results up to ten years after removal of the stent are
      published. Great care is also needed in the use of any sort of permanent device,
      either the Urolume stent, or varieties of the Strecker such as the Memotherm
      device. These should not be used in children and should be probably be avoided in
      young adults. The majority of strictures in this age group are in any case
      treated more easily by single stage urethroplasty procedures. The use of
      permanent epithelial covering stents should be limited to the bulbo-membranous
      urethra, with the possible exception of carefully selected sphincters strictures
      used in combination with an artificial urinary sphincter. Better results will be
      obtained by using these stents in strictures with a short history before multiple
      urethrotomies and dilatations have been carried out and before extensive urethral
      and periurethral fibrosis has occurred. This means that urethral rupture
      strictures are unsuitable, and in any case these are simple to deal with be means
      of stricture excision and primary end to end anastomosis of the urethra
      particularly when the stricture is in the bulbar urethra. Care must also be taken
      in using these devices in post-urethroplasty strictures if extensive periurethral
      fibrosis exists, although it has to be admitted that these stents may be very
      successful in some of these patients. The difficulty at the present time is our
      inability to define exactly which traumatic stricture or post-urethroplasty
      stricture will succeed and which will fail. Metal urethral stents should not be
      used for the first treatment of a urethral stricture. Depending on the aetiology,
      the site and the length of the stricture there is always a 40-50% chance that the
      stricture may be cured by means of a simple urethrotomy or dilatation and this
      should always be tried at least once before resorting to urethral stenting. There
      is no doubt that permanent urethral stents have an important role to play in the
      treatment of recurrent urethral strictures. Careful patient selection is
      essential in order to achieve the best results and we need more long term results
      before the final role of these devices in the treatment of urethral strictures
      can be determined. Temporary stenting of the urethra with non-epithelial covering
      stents is a simpler and safer treatment but at this point in time we cannot be
      sure how effective this treatment is and for which patients it is most
      successful. Long term results must be awaited before the place of these temporary
      devices can be defined.

PMID- 9540185
TI  - [Alternative endourologic methods for treatment of urethral stricture].
AB  - Advances in endoscopic instrumentation and techniques offer new alternatives for
      safe and effective treatment of urethral strictures. Visual internal urethrotomy,
      the standard treatment modality, is associated with new scar formation with
      stricture recurrence. This experience has led to the investigation of alternative
      techniques which would avoid or ameliorate this result. This article reviews the
      current literature and discusses these newer approaches, including balloon
      dilatation, laser urethrotomy, endoscopic urethroplasty, "cut to the light" and
      "core through" procedures, and urethral wallstent implantation.

PMID- 9540186
TI  - [Acute heart arrest during urologic routine interventions in 2 cases.
      Interdisciplinary crisis management assures tumor-free survival despite fulminant
      lung embolism with acute heart arrest during thoraco-abdominal tumor nephrectomy
      and radical cystoprostatovesiculectomy].
AB  - Intraoperative pulmonary embolism with acute cardiac arrest can successfully be
      managed by immediate open cardiac massage followed by rt-PA injection, an inter
      disciplinary approach is mandatory. The scheduled tumor nephrectomy was performed
      6 weeks after the initial event. The tumor was embolised with intravascular coils
      placed in a supraselective manner by the radiologist. During the secondary
      procedure it was found to be necrotic. In the second case the event occurred at
      the end of a radical cystectomy. Instead of an ileal conduit cutaneous
      ureterostomies were used for urinary drainage after cardiac output had been
      restored and rt-PA had been administered.

PMID- 9540187
TI  - [Transvaginal closure of vesicovaginal fistulas].
AB  - The surgical management of vesicovaginal fistulae (VVF) is a matter of
      controversy. This study deals with our experience with transvaginally treated
      patients suffering from VVF. Between 1966 and 1996, 64 patients with VVF were
      treated surgically. The VVF occurred in the course of hysterectomy in 54
      patients, was due to radiotherapy in 7, was a result of obstetric complications
      in 2 patients, and occurred after colporrhaphy in 1 patient. In 60 of these 64
      patients closure of the fistula was carried out transvaginally. Fourteen of these
      60 patients (23%) had undergone prior surgical attempts to close the VVF (1 to 3
      procedures). Transvaginal surgery was successful at first attempt in 55 of these
      60 patients (92%). The other 5 patients were successfully treated by a second
      procedure (again transvaginal: n = 3; transabdominal: n = 2). In conclusion, the
      transvaginal approach to close VVF is of advantage, avoiding an abdominal
      incision and reducing postoperative morbidity. In the vast majority of the cases
      isolated VVF can be treated successfully by transvaginal repair.

PMID- 9540188
TI  - [Does treatment with thrombocyte aggregation inhibitors modify kidney
      transplantation surgery?].
AB  - The influence of aspirin treatment on haemostasis is still under debate. There
      are doubts in emergency operations, especially in transplant patients, concerning
      dosage and change in medication. Our results are based on an analysis of the
      therapeutic approaches in German transplantation centres. The question of
      transplant suitability, dosage and haemostatic effects are discussed with respect
      to the literature. Some 92.11% of the transplantation centres perform the
      operation even though the patient has been treated with aspirin. In these cases
      an increased bleeding tendency is tolerated and observed in 34.2% of the centres.
      An increased mortality has not been reported. Most of the transplantation centres
      accept a dosage of 100 mg aspirin daily. Only 7.89% of the transplantation
      centres refuse to operate on aspirin-treated patients. Correctly indicated
      aspirin treatment (for cardiac arrhythmia, embolism, or thrombosis, for example)
      does not contraindicate renal transplantation (daily dosage up to 100 mg). In
      elective surgery, however, a preoperative change in medication is recommended,
      e.g., the heparin instead of aspirin.

PMID- 9540189
TI  - [Complete urethral rupture with symphysis injury and anterior pelvic ring
      fracture during spontaneous delivery].
AB  - We report on a complete longitudinal rupture of the urethra in combination with a
      rupture of the pubic symphysis and pelvic fracture during spontaneous vaginal
      delivery. Only after stabilisation of the pelvic fracture by external skeletal
      fixation adaptation of the urethra was possible. Three weeks later after removing
      of the transurethral catheter a mild stress incontinence could be observed. In
      the follow up one year later the patient was completely continent. The cosmetic
      result was satisfactory. There was no cystocele. An unclear haematuria after
      delivery needs a meticulous urological examination. Early repair of urethral
      disruption minimize the risk of severe incontinence. Coordinated care between the
      trauma surgeon and urologist is required for successful treatment of this rare
      combined injury after birth.

PMID- 9540190
TI  - [Combined sabal and urtica extract vs. finasteride in benign prostatic
      hyperplasia (Alken stages I to II). Comment on the contribution by J. Sokeland
      and J. Albrech].

PMID- 9540192
TI  - [A fulminant course of infection after splenectomy].
AB  - A report is given of two patients with a history of splenectomy many years
      previously due to traumatic rupture. No vaccination was given to either patient.
      From a state of good health, both patients developed fulminant, therapy-resistant
      sepsis with proof of Streptococcus pneumoniae in the blood culture. Autopsy
      findings were similar to Water-house-Friderichsen-syndrome. In conjunction with
      the history of splenectomy, the final pathological diagnosis was a so-called OPSI
      syndrome. This postsplenectomy sepsis is discussed further.

PMID- 9540193
TI  - [Urologic rehabilitation of patients with paralysis. 13th Congress of the Study
      Circle, 10-11 October 1997, Bad Wildungen].

PMID- 9540194
TI  - [Bladder carcinoma 1: Radical cystectomy, neoadjuvant and adjuvant therapy
      modalities].

PMID- 9540196
TI  - [Recommendations for billing alternative therapy of benign prostatic hyperplasia.
      Laser therapy of benign prostatic hyperplasia].

PMID- 9540197
TI  - [Transurethral high energy microwave (thermo-) therapy of benign prostatic
      hyperplasia].

PMID- 9540200
TI  - Ecstasy: 3,4-methylenedioxymethamphetamine (MDMA).
AB  - The crystal structure of 3,4-methylenedioxymethamphetamine [systematic name: N
      methyl-1-[3,4-(methylenedioxy) phenyl]-2-aminopropane] hydrochloride,
      C11H15NO2.HCl, also known as 'ecstasy' or MDMA, has been determined by X-ray
      diffraction.

PMID- 9540201
TI  - Complex network of hydrogen bonds in 3-aminopyrazole-4-carboxylic acid.
AB  - 3-Aminopyrazole-4-carboxylic acid, C4H5N3O2, crystallized in the non
      centrosymmetric space group P21 in the zwitterionic form. Intermolecular N--H...O
      hydrogen bonds with N...O distances of 2.768 (2) and 2.747 (2) A link molecules
      into two sets of chains propagating along [110] and [110]. The two sets of chains
      are crosslinked by strong hydrogen bonds. A complex network of hydrogen bonds
      ensues. There is a single intramolecular hydrogen bond. The pyrazole core is
      closely planar; the dihedral angle between the best-fit core planes of the
      molecules making up the two chains is 82.2 (1) degrees. The dihedral angles
      between the core plane and the planes of the carboxylate group and the amino
      group are in the region of 2 and 37 degrees, respectively.

PMID- 9540202
TI  - Investigation of DNA complexes with iron ions in solution.
AB  - The optical anisotropy and intrinsic viscosity of DNA-Fe3+ complexes have been
      investigated. It was shown that the binding of iron ions to DNA causes the
      shrinkage of the macromolecule. The formation of such complexes is accompanied by
      increasing DNA optical anisotropy. We suggest that the binding of iron ions to
      widely spaced along the chain DNA groups creates the conditions for initiation of
      mutually oriented DNA fragments, thus, ensuring a higher molecular optical
      anisotropy.

PMID- 9540204
TI  - Change in the binding of hydrogen ions and magnesium ions in the hydrolysis of
      ATP.
AB  - The binding of hydrogen ions and magnesium ions by a biochemical reactant, like
      ATP, can be calculated by writing the binding polynomial (partition function) Q
      and taking the partial derivatives of log Q with respect to pH and pMg by use of
      a mathematical program in a personal computer. The change in binding of hydrogen
      ions and magnesium ions in a biochemical reaction, like the hydrolysis of ATP,
      can be calculated by taking the partial derivatives of log (K'/K), where K' is
      the apparent equilibrium constant and K is the equilibrium constant for a
      reference chemical reaction. These calculations can be checked by using the
      computer to calculate the mixed partial derivatives, which must be equal. The
      effects of pH, pMg, and ionic strength on the changes in binding in the
      hydrolysis of ATP are calculated. At 298.15 K, pH7, pMg 3, and 0.25 M ionic
      strength, the hydrolysis of ATP to ADP and inorganic phosphate liberates 0.62 mol
      of hydrogen ions and 0.45 mol of magnesium ions into the medium.

PMID- 9540203
TI  - A thermodynamic study of the binding of linear and cyclic oligosaccharides to the
      maltodextrin-binding protein of Escherichia coli.
AB  - Isothermal titration calorimetric (ITC) studies over a range of temperatures of
      the binding of maltose, maltotriose, maltotetraose and beta-cyclodextrin to the
      maltodextrin-binding protein (MBP) of Escherichia coli are reported. The binding
      constants of maltose, maltotriose and beta-cyclodextrin are not very different,
      namely 8.7 x 10(5), 13.0 x 10(5) and 2.55 x 10(5) M-1, respectively at 25 degrees
      C. The calorimetric data obtained with maltotetraose cannot be interpreted in
      terms of a definite binding constant. The binding of maltose and maltotriose is
      endothermic with a large entropy increase while that of beta-cyclodextrin is
      exothermic, with a smaller entropy increase. The binding of maltotetraose was
      endothermic or exothermic depending on the temperature.

PMID- 9540205
TI  - Adsorption dynamics of L-glutamic acid copolymers at a heptane/water interface.
AB  - Random copolymers of glutamic acid (glu-ala, glu-leu, glu-phe, glu-tyr) were
      employed to investigate the relationship between side chain structure and peptide
      charge on adsorption behavior at an oil/water boundary. Adsorption of a series of
      glutamate copolymers at a heptane/water interface was examined by the dynamic
      pendant-drop method to determine interfacial tension. Incorporation of leucine or
      phenylalanine into a glutamate copolymer results in greater tension reduction
      than incorporation of alanine or tyrosine. These effects are amplified at pH
      values near the isoelectric point of glutamate, where macroscopic adsorbed films
      of glu-leu and glu-phe exhibit gel-like properties in response to interfacial
      area compression. Differences in interfacial tension behavior of glu-tyr and glu
      phe indicate the importance of the tyrosine p-hydroxyl group on adsorption and
      aggregation at the oil/water interface.

PMID- 9540206
TI  - Interaction of H(+)-ions with alpha-crystallin: solvent accessibility of
      ionizable side chains and surface charge.
AB  - Interaction of H(+)-ions with alpha-crystallin from goat lens has been studied at
      three different ionic strengths using the potentiometric titration method.
      Titrations have also been carried out in the presence of 1.5 M and 6 M GuHCl
      (guanidine hydrochloride). The isoionic pH of the protein in water and the effect
      of KCl on it have been determined. Titration curves have been found to be
      reversible between pH 3 to 9.25 at all ionic strengths. To aid in the data
      analyses, the reactivities of alpha-crystallin lysine residues to
      trinitrobenzenesulfonic acid have been determined in this work. For alpha
      crystallin aggregate, 130 +/- 2 histidine side chains out of a total of 300 and
      about 134 +/- 4 lysine side chains out of 310 have been found to be inaccessible
      to the solvent in the native condition. The remaining titratable side chains
      determine the surface charge of the native protein. In 1.5 M GuHC1, however, the
      nontitratable histidine side chains are found to be available for titration as
      are the nontitratable lysine and tyrosine side chains in 6M GuHC1. The
      theoretical titration curve computed on the basis of Linderstrom-Lang model is
      found to fit quite comfortably with the experimental one between pH 4.6 and 9.25.
      The pKint value for beta gamma-carboxyl side chains has been found to be 5.18
      which is somewhat higher than usual indicating that the carboxyl groups in the
      protein are probably in some constrained condition which is released in the
      presence of a denaturant. Below pH 4.6, there begins a conformational change in
      the alpha-crystallin aggregate as is corroborated from the circular dichroism
      studies. The value of electrostatic interaction factor w which remains more or
      less constant between pH 4.6 and 9.25 is also found to gradually fall off below
      pH 4.6.

PMID- 9540207
TI  - Structural polymorphism in a tubercidin analogue of the DNA double helix.
AB  - A high-angle X-ray fibre diffraction study of a tubercidin analogue of the
      poly[d(A-T)].poly[d(A-T)] DNA double helix has been carried out using station 7.2
      at the Daresbury Laboratory synchrotron radiation source. The polymer has been
      studied for a wide range of salt strengths and hydration conditions and exhibits
      conformational polymorphism that is quite distinct from that observed for the
      unmodified polymer. The replacement of deoxyadenosine by deoxytubercidin in the
      polynucleotide causes only slight alterations to the structure of A-DNA, but
      significantly alters the structure of the B conformation. Additionally, the
      modified polymer does not, in any conditions yet identified, adopt the D
      conformation. In conditions which would normally favour the D conformation of
      poly[d(A-T)].poly[d(A-T)], the modified polymer adopts an unusual conformation
      which is designated here as the K conformation. These observations are important
      for an understanding of major groove interactions involved in the stabilisation
      of particular DNA conformations and also more generally for an insight into the
      pharmacological activity of tubercidin which following its incorporation into
      nucleic acids may cause stereochemical distortions of the DNA double helix.

PMID- 9540208
TI  - Electrostatic effects on protein partitioning in size-exclusion chromatography
      and membrane ultrafiltration.
AB  - Although size-exclusion chromatography and membrane ultrafiltration are generally
      viewed as size-based separation processes, there is considerable evidence for the
      importance of electrostatic interactions. Experimental studies of size-exclusion
      chromatography and membrane ultrafiltration were performed in parallel using both
      neutral dextrans and charged proteins. Data for protein retention time and
      membrane sieving clearly indicate that the effective protein size increases with
      decreasing ionic strength due to the reduction in electrostatic shielding. These
      results were quantified using available theoretical models for the partitioning
      of charged solutes. The data clearly demonstrate the similarity of the
      electrostatic interactions and partitioning effects in size-exclusion
      chromatography and membrane ultrafiltration.

PMID- 9540209
TI  - Simulated moving bed chromatographic resolution of a chiral antitussive.
AB  - The behavior of a laboratory simulated moving bed (SMB) unit for continuous
      chromatographic separation of enantiomers has been considered. This was applied
      to the resolution of a chiral antitussive agent, guaifenesin, on Chiralcel OD,
      during an experimental campaign involving nineteen runs. The application of
      recently developed criteria for the design and optimization of SMB units allows
      us to understand and rationalize the experimental results, as well as to indicate
      how to optimize the separation performances. A three-step procedure to determine
      the adsorption isotherms needed to apply these criteria is proposed; it is
      reliable and may be applied also where pure components are not available.

PMID- 9540210
TI  - Size-exclusion chromatography of plasma proteins with high molecular masses.
AB  - Two different hydrophilic materials with large pores, Superose 6 and Fractogel
      EMD BioSec (S), which are designed for size-exclusion chromatography (SEC) of
      plasma proteins with high molecular masses, are tested for their performance on a
      preparative scale. The model mixtures are preparations of the clotting factors
      VIII (FVIII) and IX (FIX). A combination of a Fractogel EMD BioSec (S) column and
      a Superose 6 column has proved to be particularly effective for separations in a
      wide molecular size range, from several millions down to about 20,000. Superose 6
      showed good results on a small scale as well as on a large scale, even in the
      molecular mass range over 1,000,000. However, recovery of FVIII clotting activity
      was less than 70% with this material and therefore not satisfactory. Fractogel
      did not perform well in terms of separation on a small scale. However, in the
      case of biopolymers with high molecular masses, separation was improved by using
      larger columns. With Fractogel, recovery of activity of the two clotting factors
      FVIII and FIX was satisfactory, above 80%. On a large scale, the active fraction
      in the clotting factor concentrate was successfully separated from the non-active
      fraction with either size exclusion (SE) material. In the preparation under
      investigation, the clotting factor VIII is found in a complex with the von
      Willebrand factor (vWF). The FVIII-vWF complex has a molecular mass of several
      millions. It dissociates in the presence of high concentrations of Ca2+ ions.
      Under such conditions FVIII and vWF were successfully separated with both SEC
      columns.

PMID- 9540211
TI  - Determination of aryloxyphenoxypropionic acid herbicides in water using different
      solid-phase extraction procedures and liquid chromatography-diode array
      detection.
AB  - For isolation and trace enrichment of aryloxyphenoxypropionic acid (ArPP)
      herbicides from drinking, spring, and ground water a sensitive, robust method is
      presented. A 1-2 1 volume of aqueous samples was passed through a disposable
      solid-phase extraction cartridge, packed with 500 mg of Carbograph-1 at a flow
      rate of 100 ml/min. After washing, ArPPs are selectively eluted with 8 ml of
      dichloromethane-methanol (80:20, v/v) with 50 mmol/1 formic acid and evaporated
      to dryness. The mixture was reconstituted with 250 microliters of water
      acetonitrile (75:25; v/v) acidified with 0.1% trifluoroacetic acid and 100
      microliters was injected into the high-performance liquid chromatography system.
      The ArPPs were separated via a binary gradient of water and a mixture of methanol
      acetonitrile. Detection and confirmation were performed by diode array detection.
      Recovery of the six acid herbicides ranged between 90% and 98%. The limits of
      detection of ArPPs were 7-20 ng/l for drinking water and 16-36 ng/l for spring
      water. In terms of recovery and selectivity the effectiveness of Carbograph-1
      cartridges was compared with that of LiChrolut-EN cartridges and polystyrene
      divinylbenzene Empore disks. Relevant parameters such as pH and flow-rate for
      solid-phase extraction with divinylbenzene resins were optimized.

PMID- 9540212
TI  - High-performance liquid chromatography determination of direct and temporary dyes
      in natural hair colourings.
AB  - A simple and reliable HPLC method is described for the simultaneous determination
      of nine direct and temporary hair dyes in hair colourings containing vegetal
      extracts. Detection was performed by a diode array detector and two different
      wavelengths, in the visible range (450 and 650 nm), were used for quantitation.
      The method does not involve any extraction procedure and it is sufficiently rapid
      and accurate for routine analyses. The method described was successfully applied
      to the identification of synthetic organic dyes in 13 direct and temporary hair
      dyeing formulations commercialized as 'natural'.

PMID- 9540213
TI  - Cyclodextrin aided separation of peptides and proteins by capillary zone
      electrophoresis.
AB  - Carboxymethylated-beta-cyclodextrin (CMBCD) in the electrophoretic medium
      (aqueous 50 mM sodium phosphate, pH 2.5) enhanced the separation using raw fused
      silica capillaries in CZE of the four standard proteins: alpha-chymotrypsinogen
      A, cytochrome c, lysozyme and ribonuclease A. Furthermore, with 20 mM CMBCD in
      the electrophoretic medium, the cis-trans isomers of angiotensin could be
      separated at room temperature, whereas the separation of the conformers required
      subambient temperatures as low as -20 degrees C without CMBCD in the
      electrophoretic medium [50 mM sodium phosphate (pH 2.5), containing 10% (v/v)
      methanol]. Addition of heptakis(2,6-di-O-methyl)-beta-cyclodextrin (DMBCD) had no
      effect on the separation of the above proteins and peptides. The results suggest
      that in microcolumn separation techniques, certain cyclodextrin additives can be
      useful selectivity enhancers.

PMID- 9540214
TI  - Mitochondrial photodamage and PDT-induced apoptosis.
AB  - Four photosensitizers with specific targets (mitochondria, lysosomes and plasma
      membrane) were used to delineate the mechanism of PDT-induced apoptosis in murine
      leukemia cells. Additional studies were carried out with two sensitizers which
      caused photodamage to both mitochondria and lysosomes, but varied with regard to
      membrane photodamage. PDT induced an apoptotic response after mitochondrial
      photodamage, but not after selective damage to lysosomes or to the cell membrane.
      Moreover, the latter could delay or inhibit the appearance of apoptosis after
      mitochondrial photodamage. We had previously reported that exposure of cells to
      high porphycene concentrations caused an apoptotic response in the dark; this was
      also associated with mitochondrial damage. These results are consistent with
      recent proposals that release of mitochondrial components can trigger an
      apoptotic response. ATP depletion after mitochondrial photodamage does not appear
      to play a role in initiation of the apoptotic program.

PMID- 9540215
TI  - Photodynamic therapy for lung cancer--a review of 19 years' experience.
AB  - This paper reviews studies of photodynamic therapy for the treatment of lung
      cancer in Japan, carried out since 1978. Photodynamic therapy has been applied
      clinically to both early and advanced stages of lung cancer and in combination
      with surgery. It can preserve pulmonary function, is well tolerated and is cost
      effective in comparison with other treatments.

PMID- 9540216
TI  - In vivo fluorescence of phthalocyanines during light exposure.
AB  - Nude mice were given AlPcS2a (aluminum phthalocyanine disulfonate) and AlPcS4
      (aluminum phthalocyanine tetrasulfonate) by intraperitoneal injections. After
      time intervals of 1-48 hours the mice were exposed to 150 mW cm-2 light at 670 nm
      and the phthalocyanine fluorescence was measured during light exposure. During
      the first few minutes of light exposure the phthalocyanine fluorescence of the
      skin of the mice increased by up to a factor of two, indicating lysosomal
      localization of the dye and permeabilization of the lysosomes. The process did
      not occur in the skin of dead mice, indicating that the process was dependent on
      oxygen.

PMID- 9540217
TI  - Differential photosensitivity in wild-type and mutant p53 human colon carcinoma
      cell lines.
AB  - Tumor sensitivity to cancer therapies may be modulated by the p53 status of the
      malignant cells. Generally, tumors retaining wild-type p53 are more sensitive to
      radiotherapy and some chemotherapeutic agents than are tumors with either a
      mutated or deleted p53 phenotype. The role of p53 in the responsiveness to PDT as
      a cancer treatment is clinically unknown. In the current study, we evaluated the
      photosensitivity of two human colon carcinoma cell lines, one expressing wild
      type p53 protein and the other expressing mutant p53. Wild-type p53 cells were
      found to be significantly more sensitive to Photofrin-mediated photodynamic
      treatment measured by clonogenic assay. Uptake of the photosensitizer was
      equivalent for both cell lines. Interestingly, sensitivity of the colon carcinoma
      cell lines to ionizing radiation was similar. These two cell lines represent a
      useful model for examining p53 involvement in the cellular response to PDT
      mediated oxidative stress.

PMID- 9540218
TI  - Thionucleobases as intrinsic photoaffinity probes of nucleic acid structure and
      nucleic acid-protein interactions.
AB  - In the past few years thionucleobases have been extensively used as intrinsic
      photolabels to probe the structure in solution of folded RNA molecules and to
      identify contacts within nucleic acids and/or between nucleic acids and proteins,
      in complex nucleoprotein assemblies. These thio residues such as 4-thiouracil
      found in E. coli tRNA and its non-natural congeners 4-thiothymine, 6-thioguanine
      and 6-mercaptopurine absorb light at wavelengths longer than 320 nm and, thus,
      can be selectively photoactivated. Synthetic or enzymatic procedures have been
      established, allowing the random or site-specific incorporation of
      thionucleotide(s) within a RNA (DNA) chain which, in most cases, retains
      unaltered structural and biological properties. Owing to the high photoreactivity
      of their triplet state (intersystem yield close to unity), 4-thiouracil and 4
      thiothymine derivatives exhibit a high photocrosslinking ability towards
      pyrimidines (particularly thymine) but also purines. From the nature of the
      photoproducts obtained in base or nucleotide mixtures and in dinucleotides, the
      main photochemical pathway was identified as a (2 + 2) photoaddition of the
      excited C-S bond onto the 5, 6 double bond of pyrimidines yielding thietane
      intermediates whose structure could be characterized. Depending on the mutual
      orientation of these bonds in the thietanes, their subsequent dark rearrangement
      yielded, respectively, either the 5-4 or 6-4 bipyrimidine photoadduct. A similar
      mechanism appears to be involved in the formation of the unique photoadduct
      formed between 4-thiothymidine and adenosine. The higher reactivity of thymine
      derived acceptors can be explained by an additional pathway which involves
      hydrogen abstraction from the thymine methyl group, followed by radical
      recombination, leading to methylene linked bipyrimidines. The high
      photocrosslinking potential of thionucleosides inserted in nucleic acid chains
      has been used to probe RNA-RNA contacts within the ribosome permitting, in
      particular, the elucidation of the path of mRNA throughout the small ribosomal
      subunit. Functional interactions between the mRNA spliced sites and U RNAs could
      be detected within the spliceosome. Analysis of the photocrosslinks obtained
      within small endonucleolytic ribozymes in solution led to a tertiary folded
      pseudo-knot structure for the HDV ribozyme and allowed the construction of a Y
      form of a hammerhead ribozyme, which revealed to be in close agreement with the
      structure observed in crystals. Thionucleosides incorporated in nucleic acids
      crosslink efficiently amino-acid residues of proteins in contact with them.
      Despite the fact that little is known about the nature of the photoadducts
      formed, this approach has been extensively used to identify protein components
      interacting at a defined nucleic acid site and applied to various systems
      (replisome, spliceosome, transcription complexes and ribosomes).

PMID- 9540219
TI  - Pulse radiolysis studies of melatonin and chloromelatonin.
AB  - The endogenous indole melatonin and the melatonin receptor agonist 6
      chloromelatonin block the proliferation of both dermal and uveal melanoma cells
      by mechanisms that may involve redox reactions. The interactions of hydrated
      electrons, the azide radical, hydroxyl radicals and superoxide with melatonin and
      its 6-chloro analogue have been studied using the technique of pulse radiolysis.
      The reaction rate constants of eaq- and N3 x with these compounds were found to
      be dependent on substitution at the sixth position. The rate constants for
      reaction of 6-chloromelatonin and melatonin with solvated electrons are 4.5 x
      10(9) M-1 s-1 and 4.2 x 10(8) M-1 s-1, respectively. The reaction rate constants
      of N3 x with malatonin and chloromelatonin are 9.8 x 10(9) M-1 s-1 and 3.5 x
      10(9) M-1 s-1 and 3.5 x 10(9) M-1 s-1, respectively. Melatonin and 6
      chloromelatonin react with hydroxyl radicals at near diffusion controlled rates
      (1.3 x 10(10) M-1 s-1, 8.2 x 10(9) M-1 s-1). Melatonin and 6-chloromelatonin did
      not react with superoxide radicals and we calculate an upper limit of 1.0 x 10(4)
      M-1 s-1 for the rate constant for reaction of melatonin and 6-chloromelatonin
      with superoxide ion.

PMID- 9540220
TI  - Fluorescence spectroscopy and photochemistry of phytochromes A and B in wild
      type, mutant and transgenic strains of Arabidopsis thaliana.
AB  - Phytochrome (P) was characterized in etiolated seedlings of wild-type, mutant and
      transgenic strains of Arabidopsis with the use of low-temperature (85 K)
      fluorescence spectroscopy and photochemistry. The position (lambda max) of the Pr
      emission spectrum, its intensity (F0) proportional to [P tot] and the extent of
      the Pr-->lumi-R phototransformation at 85 K (gamma 1) were shown to vary
      depending on the plant strains and tissues used, while the extent of the Pr-->Pfr
      transformation at 273 K (gamma 2) remained relatively constant. Depletion of phyA
      (fre1-1 in Nagatani et al., Plant Physiol. 102 (1993) 269-277, and fhy2-2 in
      Whitelam et al., Plant Cell 5 (1993) 757-768) resulted in a steep decrease of F0
      to approximately equal to 10%. The phyB mutant (hy3-B064 in Reed et al., Plant
      Cell 5 (1993) 147-157) revealed a slight reduction (by approximately equal to
      20%) of F0 while lambda max and gamma 1 remained practically unaffected. In
      phyAphyB mutuant no P emmission was observed. Overexpression of oat phyA (13k7
      and 21k15 in Boylan and Quail, Proc. Natl. Acad. Sci. USA 88 (1991) 10806-10810)
      brought about an increase of F0 by two or three times, a shift of lambda max to
      685 nm and an increase of gamma 1 to 0.3-0.4. On the contrary, an increase of F0
      (up to 40%) in Arabidopsis and rice phyB overexpressors (ABO and RBO in Wagner et
      al., Plant Cell 3 (1991) 1275-1288) was followed by a decrease of gamma 1 values
      to 0.13-0.14. These data together with the results on phyB (lh) mutant of
      cucumber prove the existence of the two phyA populations with high (phyA') and
      low (phyA") photochemical activity at low temperatures. PhyB emits maximally in
      the same region as phyA in Arabidopsis (approximately equal to 683 nm) and at
      shorter wavelength (< 680 nm) in rice. It is characterized by low photochemical
      activity at 85 K (gamma 1 < or = 0.05) and can be attributed in this respect to
      the same pigment type as phyA".

PMID- 9540221
TI  - Photodynamic action of uroporphyrin and protochlorophyllide in greening barley
      leaves treated with cesium chloride.
AB  - Incubation of greening barley leaves with cesium chloride (CsCl) results in
      photodynamic leaf lesions within 24 h due to an inactivation of uroporphyrinogen
      III decarboxylase, an enzyme of tetrapyrrole biosynthesis, and transient
      accumulation of uroporphyrin (ogen). To examine the mechanism of
      porphyrinogenesis, time kinetics of the accumulating tetrapyrrole intermediates
      uroporphyrin (ogen) and protochlorophyllide were performed with leaves which were
      cut from 7-day-old dark-grown barley seedlings and incubated in 15 mM CsCl or
      water under different light regimes. In the presence of CsCl chlorophyll and
      carotenoids accumulation was inhibited in the first 24 h of continuous light and
      the pigment content decreased dramatically during extended illumination. When
      CsCl=treated leaves were transferred to darkness, accumulated uroporphyrinogen
      was completely converted to protochlorophyllide. Low temperature fluorescence
      spectroscopy confirmed that uroporphyrinogen almost completely accumulated in the
      reduced form. The oxidised form, uroporphyrin, was detectable after 24 h of
      illumination. The photodynamic leaf lesions became visible at the same time.
      Protochlorophyllide synthesised from accumulated uroporphyrinogen III in dark
      incubated leaves had a fluorescence maximum at 635 nm which is indicative for its
      non-photoconvertible form. Re-illumination of the barley leaves resulted in a
      rapid degradation of proteins and pigments and an intense lipid peroxidation
      within less than two hours due to the photodestructive potential of non
      metabolised protochlorophyllide.

PMID- 9540222
TI  - The induction of apoptosis by a positively charged methylene blue derivative.
AB  - Identifying the cellular responses to photodynamic therapy (PDT) is important if
      the mechanisms of cell death are to be fully understood. PDT with a methylene
      blue analog DO15 yielded mitochondrial photodamage whilst membrane and lysosomal
      integrity were maintained. Apoptosis was detected using the DNA stain HO342, by
      the appearance of 50 kb fragments and by DNA ladder formation. The release of
      mono- and oligonucleosomes was further quantified using an ELISA protocol. Large
      DNA fragments were observed immediately following illumination, and nucleosomes
      were detected at 1-2 h post-treatment. Increasing the dose 4-fold accelerated the
      apoptotic response to PDT. This is the first report of a thiazine photosensitiser
      inducing apoptosis and is consistent with recent proposals suggesting that
      release of mitochondrial components may play an important role in the mechanism
      of cell death.

PMID- 9540223
TI  - Personality comparison between children of hidden Holocaust survivors and
      American Jewish parents.
AB  - The possibility that the experiences of the "hidden" child survivors of the
      Holocaust (those who survived outside of the concentration camps during the Nazi
      occupation) had a pathological effect on their offspring was examined by
      comparing volunteer, matched samples of adult children of "hidden" child
      survivors of the Holocaust with adult children of nontraumatized U.S.-born Jewish
      parents on personality variables measured by the Sixteen Personality Factor
      Questionnaire (Cattell, Eber, & Tatsuoka, 1970). The MANOVA results indicated
      that there were no differences in the personality characteristics of the two
      groups.

PMID- 9540224
TI  - The anticipated transition to adulthood: effects of culture and individual
      experience on Polish and Finnish adolescents' future orientations.
AB  - The purpose of this study was to describe the effect of a set of individual
      resources and cultural factors on adolescents' probability estimations of the
      occurrence of positive future events in three life domains: education,
      occupation, and family. The hypothesis was that the effects of culture and
      individual resources are interwoven in the formation process of future
      orientation. The sample consisted of 352 17-year-old Polish and Finnish girls and
      boys from vocational and upper secondary schools. The 78-item questionnaire
      developed by the authors was used to measure different aspects of future
      orientation (probability, valence, and extension of future events in three life
      domains) and individual resources (self-esteem, control beliefs, and social
      knowledge about normatively and the generation gap). Data analysis showed that
      culture separately affected individual resources and adolescents' expectations.
      However, the results broadly confirmed the thesis that the culture has a limited
      effect on adolescents' expectations of the occurrence of future events. Moreover,
      these data suggested that the influence of sociocultural differences on
      adolescents' probability estimations is indirect. In the context of the presented
      data, the authors discuss their model of future orientation.

PMID- 9540225
TI  - Interaction of humor and gender in moderating relationships between stress and
      outcomes.
AB  - This study is an examination of the interaction of humor and gender in moderating
      relationships among perceived stress, anxiety, and physical symptoms.
      Introductory psychology students (70 women, 61 men) completed self-report scales
      measuring perceived stress, humor, and symptomology. Multiple regression analyses
      revealed a moderating effect for humor between stress and anxiety, but only for
      men. When humor was low, a positive relationship was obtained between stress and
      anxiety; no relationship existed when humor was high. No gender differences were
      found in the significant moderating effect of humor between stress and physical
      symptoms. When humor was low, stress was related to physical symptoms; no
      relationship was found when humor was high. Overall, the findings supported humor
      as a moderator of stress; gender differences also existed for some outcomes.

PMID- 9540226
TI  - The influence of job satisfaction, organizational commitment, and fairness
      perceptions on organizational citizenship behavior.
AB  - Previous research has indicated that job satisfaction, perceptions of procedural
      justice, and organizational commitment are all significant correlates of
      organizational citizenship behavior (OCB). Those variables were studied
      collectively to determine their relative effects on OCB. Hierarchical regression
      analyses indicated that when all three of the variables were considered
      concurrently, only organizational commitment accounted for a unique amount of
      variance in OCB.

PMID- 9540227
TI  - Self-evaluation processes of African American youth in a high school completion
      program.
AB  - In the present study, regression analyses were used to determine whether
      particular domains of perceived competence, alienation from school, and cultural
      mistrust of society in general predicted judgments of global self-worth and
      global self-discrepancy in a group of African American high school dropouts in a
      compensatory program. The participants were 31 African American high school
      dropouts between 16 and 24 years of age (M = 17.7 years, SD = 1.81) who were
      enrolled in a state-sponsored high school completion program. Perceived job
      competence and peer-related social competence were the most significant
      predictors of self-evaluations. Cultural mistrust of society was associated with
      students' self-evaluation and overshadowed alienation from school in the
      prediction of global self-worth. The implications of these results for
      interventions with African American high school dropouts in this type of program
      are discussed.

PMID- 9540228
TI  - Family capital, children's individual attributes, and adolescents' aspirations: a
      follow-up analysis.
AB  - In this follow-up study of an earlier investigation (Marjoribanks, 1992),
      relationships were examined between family capital, children's individual
      attributes, immediate family settings, and adolescents' aspirations. There were
      500 Australian adolescents (250 girls, 250 boys) and their parents in the sample.
      The results of this study and of the earlier investigation suggest that (a)
      family environmental contexts are moderately to largely associated with
      children's academic performances and adolescents' aspirations; (b) relationships
      between family contexts, children's individual attributes, and adolescents'
      aspirations are mediated fully or in part by adolescents' perceptions of their
      parents' support for learning; and (c) there are gender-related differences in
      the nature of the associations among family capital, individual attributes,
      immediate family settings, and adolescents' aspirations.

PMID- 9540230
TI  - Procrastination by pigeons with fixed-interval response requirements.
AB  - Two experiments studied the phenomenon of procrastination, in which pigeons chose
      a larger, more delayed response requirement over a smaller, more immediate
      response requirement. The response requirements were fixed-interval schedules
      that did not lead to an immediate food reinforcer, but that interrupted a 55-s
      period in which food was delivered at random times. The experiments used an
      adjusting-delay procedure in which the delay to the start of one fixed-interval
      requirement was varied over trials to estimate an indifference point--a delay at
      which the two alternatives were chosen about equally often. Experiment 1 found
      that as the delay to a shorter fixed-interval requirement was increased, the
      adjusting delay to a longer fixed-interval requirement also increased, and the
      rate of increase depended on the duration of the longer fixed-interval
      requirement. Experiment 2 found a strong preference for a fixed delay of 10 s to
      the start of a fixed-interval requirement compared to a mixed delay of either 0
      or 20 s. The results help to distinguish among different equations that might
      describe the decreasing effectiveness of a response requirement with increasing
      delay, and they suggest that delayed reinforcers and delayed response
      requirements have symmetrical but opposite effects on choice.

PMID- 9540229
TI  - Mechanisms underlying the effects of unsignaled delayed reinforcement on key
      pecking of pigeons under variable-interval schedules.
AB  - Three experiments were conducted to test an interpretation of the response-rate
      reducing effects of unsignaled nonresetting delays to reinforcement in pigeons.
      According to this interpretation, rates of key pecking decrease under these
      conditions because key pecks alternate with hopper-observing behavior. In
      Experiment 1, 4 pigeons pecked a food key that raised the hopper provided that
      pecks on a different variable-interval-schedule key met the requirements of a
      variable-interval 60-s schedule. The stimuli associated with the availability of
      the hopper (i.e., houselight and keylight off, food key illuminated, feedback
      following food-key pecks) were gradually removed across phases while the
      dependent relation between hopper availability and variable-interval-schedule key
      pecks was maintained. Rates of pecking the variable-interval-schedule key
      decreased to low levels and rates of food-key pecks increased when variable
      interval-schedule key pecks did not produce hopper-correlated stimuli. In
      Experiment 2, pigeons initially pecked a single key under a variable-interval 60
      s schedule. Then the dependent relation between hopper presentation and key pecks
      was eliminated by arranging a variable-time 60-s schedule. When rates of pecking
      had decreased to low levels, conditions were changed so that pecks during the
      final 5 s of each interval changed the keylight color from green to amber. When
      pecking produced these hopper-correlated stimuli, pecking occurred at high rates,
      despite the absence of a peck-food dependency. When peck-produced changes in
      keylight color were uncorrelated with food, rates of pecking fell to low levels.
      In Experiment 3, details (obtained delays, interresponse-time distributions,
      eating times) of the transition from high to low response rates produced by the
      introduction of a 3-s unsignaled delay were tracked from session to session in 3
      pigeons that had been initially trained to peck under a conventional variable
      interval 60-s schedule. Decreases in response rates soon after the transition to
      delayed reinforcement were accompanied by decreases in eating times and
      alterations in interresponse-time distributions. As response rates decreased and
      became stable, eating times increased and their variability decreased. These
      findings support an interpretation of the effects of delayed reinforcement that
      emphasizes the importance of hopper-observing behavior.

PMID- 9540231
TI  - Coronary reactive hyperaemia after nitric oxide inhibition in the anaesthetized
      goat.
AB  - In the dog it has been shown that, while the inhibition of the endothelial
      release of nitric oxide reduces the duration, the total hyperaemic flow and the
      peak flow of the acetylcholine and myogenic coronary vasodilator responses, in
      the reactive hyperaemia the peak is not affected. The difference has been
      attributed to the different time required by the coronary blood flow to reach its
      maximum: long enough when acetylcholine is given or myogenic vasodilatation is
      elicited, this time is very short in the reactive hyperaemia. Thus it has been
      argued that only when the time to the peak of a hyperaemic response is
      sufficiently long, the increased shear stress acting on the coronary endothelium
      at the beginning of the hyperaemia can enhance the maximum value of the
      vasodilatation. Such an effect is impaired by NO-inhibition. Since in the goat
      the time to the peak of the coronary reactive hyperaemia is much longer than in
      the dog (10-14 s vs 3-4 s), the present study aimed at investigating whether the
      same effect caused by the NO-inhibition on the maximum flow of the acetylcholine
      and myogenic hyperaemic responses in the dog, can also be obtained in the goat
      for the peak flow of the coronary reactive hyperaemia. Experiments performed in
      anaesthetised goats showed that NO-inhibition reduces the duration of the
      reactive hyperaemia without affecting the maximum hyperaemic flow. It is
      suggested that in the reactive hyperaemia the large predominance of metabolic
      factors prevents the shear stress from playing a role in enhancing the peak flow.

PMID- 9540232
TI  - Regulation of IGFBP-1 and -4 expression by triiodothyronine (T3) in cultured
      hepatocytes is cell- and gene-specific.
AB  - Evidence suggests that thyroid hormone plays a role in the regulation of hepatic
      IGF/IGFBP expression both in human and rats. In this study we compared the effect
      of T3 on IGFBP-1 and -4 expression in rat hepatocyte primary cultures and in the
      human hepatoma cell line HepG2. Northern blot analysis revealed that IGFBP-1 mRNA
      levels were not affected by T3 in cultured rat hepatocytes, whereas a net
      increase of IGFBP-1 transcript abundance was induced by the hormone in HepG2
      cells. On the contrary, IGFBP-4 mRNA levels were increased in rat hepatocytes
      cultured in the presence of T3, but unaffected in T3-treated HepG2 cells.
      Therefore, thyroid hormone seems to regulate hepatic IGFBP expression in a direct
      and gene-specific way. Moreover, the effects of thyroid hormone depend strictly
      on the source of target hepatocyte.

PMID- 9540234
TI  - Modelling survival kinetics for red blood cells.
AB  - In the attempt to improve the analysis of red blood cell survival kinetics we
      evaluated the ability of a new mathematical model of survivorship in fitting
      hemolysis curves. This model contains two parameters omega and S0 related to
      deterministic and stochastic components of mortality kinetics, respectively. In
      this paper, firstly, we show that the model can be usefully applied in the
      analysis of hemolysis kinetics of very different life span and shape. Then, we
      check the capability of fitting the model to experimental lysis curves derived
      from human erythrocytes incubated at different temperatures: our results
      demonstrate that there is good agreement between experimental and theoretical
      data.

PMID- 9540233
TI  - The potential role of FLT3 ligand in progenitor and primitive hematopoietic cell
      expansion.
AB  - We have previously defined the experimental conditions for hematopoietic cell
      expansion. CD34+ human marrow cells were maintained in a serum-free, stroma-free
      liquid culture system, at a concentration of 10(3) cells/ml, for 10 days at 37
      degrees C, in the presence of various cytokine combinations. The basic
      combination of early cytokines SCF (100 ng/ml), IL3 (5 ng/ml), IL6 (10 ng/ml),
      has a modest stimulating effect on all compartments: the number of total cells
      increased 56-fold and CD34+ cells 1-fold; CFU-GM, BFU-E and CFU-MK, increased 6
      fold, 5-fold and 3-fold respectively. As far as CD34+ cells are concerned, the
      subpopulation CD34+/CD38- was only maintained. Interestingly, the addition of 100
      ng/ml of Flt3 ligand (FL) significantly enhanced the amplification of total cells
      (276-fold), CFU-GM (54-fold) and BFU-E (15-fold). The number of CD34+ cells and
      the subpopulation CD34+/38- increased to 7-fold and 22-fold respectively.
      Moreover, long term culture-initiating cells (LTC-ICs) in limiting dilution assay
      (LDA) were found to increase 3-fold. Further addition of MGDF (10 ng/ml), G-CSF
      (10 ng/ml) and Epo (0.5 U/ml), in various combinations, acted synergically with
      the previous cytokine combination to support the formation of multiple types of
      hematopoietic colonies. As expected, the addition of MGDF increased the number of
      CFU-MK up to 5-fold expansion. Interestingly, MGDF addition was synergistic also
      for BFU-E and CFU-GM expansion. In the combination of SCF+ IL3+ IL6+ FL + MGDF,
      CFU-GM expanded to 73-fold and BFU-E to 17-fold. G-CSF in SCF + IL3 + IL6 + FL
      conditions stressed the expansion of the granulopoietic compartment doubling the
      number of CFU-GM and CD33+ cells, with no consequence on LTC-IC or BFU-E.
      Surprisingly, G-CSF induced the expansion of the megakaryocytic lineage up to 6
      fold, in a similar way as MGDF. Epo in presence of SCF+ IL3+ IL6+/-FL
      dramatically increased total cell expansion (2300-2800-fold), mainly
      erythroblastic (70% glycoA) without exhaustion of all other compartments. The
      simultaneous use of these three cytokines (MGDF + G-CSF + Epo) in presence of
      four early cytokines (SCF + IL3 + IL6 + FL) clearly allows a significant
      expansion of all hematopoietic compartments, precursors, progenitors, and
      primitive stem cells. In conclusion, these data show the ability of a stroma
      free, serum-free liquid system to expand all myeloid lineages, including CFU-MK
      and LTC-IC which are critical for clinical application of ex vivo expanded cells.

PMID- 9540235
TI  - Cell death and cell proliferation contribute to the enhanced growth of foci by
      fasting in rat medial colon.
AB  - We have recently shown that fasting before initiation markedly stimulated the
      growth of aberrant crypt foci (ACF) induced by azoxymethane (AOM) in the rat
      medial colon. Here we investigated the mechanisms by which fasting enhanced the
      growth of ACF. Rats were exposed to 4 day-starvation, then they were given AOM
      (20 mg/kg) on the first day of refeeding. 4 day-fasting depressed cell
      proliferation as shown by the decreased mitotic index and enhanced cell death by
      apoptosis. On the first day of refeeding, apoptotic index remained higher than
      control values, while mitotic index markedly increased in the colonic epithelium
      of fasted/ refed rats. The administration of AOM induced an apoptotic wave, that
      was higher in controls, and a transient drop in the mitotic index that recovered
      quickly in the fasted/refed group. These data suggest that starvation-induced
      apoptosis represents the mitogenic stimulus to increase the rates of cell
      proliferation responsible for the enhanced growth of ACF in fasted/refed rats.

PMID- 9540236
TI  - Hypotonic-hyporesponsive episodes in children hospitalized at 10 Canadian
      Pediatric Tertiary-Care Centres, 1991-1994.

PMID- 9540238
TI  - Children with both developmental and behavioral needs: profile of two clinic
      populations.
AB  - Little has been written about evaluation and intervention services for children
      with a combination of behavioral and developmental needs. Two multidisciplinary
      clinic populations were compared, a traditional Developmental Disabilities (DD)
      clinic and a Behavioral-Developmental Problems (BDP) Clinic that had the
      additional services of a child psychiatrist. The BDP clinic children had lower
      IQ's and more severe overall behavioral problems than children in the traditional
      DD clinic, but differences were not statistically significant. Children with
      Attention Deficit Hyperactivity Disorder (ADHD) and other psychiatric diagnoses
      were referred to both clinics at comparable rates. The effort to involve
      qualified mental health professionals in all aspects of professional training and
      clinical service for the DD population should be accelerated.

PMID- 9540239
TI  - Childhood vs. adolescence transitional object attachment, and its relation to
      mental health and parental bonding.
AB  - 871 participants, 375 boys and 496 girls, mean age 16.7 + 1, were administered
      the Parental Bonding Instrument (P.B.I.), the Brief Symptom Inventory (B.S.I.),
      the General Well-Being Questionnaire (G.W.B.) and the Chestnut Lodge Transitional
      Object Scale. Results supported Winnicott's theory: participants reporting
      attachment to a Transitional Object (T.O.) in their childhood reported
      significantly more optimal maternal bonding than participants who were not
      attached to a T.O. Participants reporting attachment to a T.O. in adolescence had
      significantly more psychiatric symptoms and less general well-being. Adolescence
      T.O. attachment might be considered a marker of mental distress in the general,
      normal population.

PMID- 9540240
TI  - Parental hostility: impact on the family.
AB  - This study examined the effects of parental hostility on the families of 100
      psychiatrically hospitalized children. Parents and their children were
      administered an assessment battery. The results for families who scored high on
      parental hostility were compared to families with low parental hostility. Parents
      who exhibited high hostility scored differently on a variety of temperament
      constructs (e.g., lower adaptability, worse mood, and lower rhythmicity) than
      parents who scored low in hostility. High parental hostility was also associated
      with an elevated level of family relation problems, which includes family
      effectiveness and cohesion.

PMID- 9540241
TI  - Clinical evaluation of attention-deficit hyperactivity disorder by objective
      quantitative measures.
AB  - This study assessed the diagnostic potential of the actigraph, the Continuous
      Performance Test, and the Matching Familiar Figures Test in diagnosing attention
      deficit hyperactivity disorder (ADHD). Twenty boys previously diagnosed with ADHD
      and 52 controls were examined. By these measures the boys with ADHD were
      differentiated from the controls with sensitivity and specificity above 75%. We
      were able to classify ADHD into eight subtypes by combining the scores of the
      actigraph and the CPT: "hyperactive-impulsive", "hyperactive-inattentive",
      "impulsive-inattentive", "hyperactive", "impulsive", "inattentive", "mixed", and
      "unspecified" type. These classifications may be useful in diagnosing ADHD.

PMID- 9540242
TI  - Defense style and family environment.
AB  - Prospective observations of the defense styles of normal individuals suggest that
      the quality of the childhood family environment may influence the maturity of
      defense styles used in adulthood. In this study, 106 female adolescent
      psychiatric patients completed the Defense Style Questionnaire, and the Family
      Environment Scale (FES). Positive family characteristics such as cohesion and
      expressiveness, as measured by the FES, were correlated with the report of Mature
      Defenses. Negative family characteristics such as conflict were correlated with
      the report of Immature Defenses. Similar although weaker correlations were found
      after controlling for the effects of depression and defensiveness on the self
      report measures.

PMID- 9540243
TI  - Making a successful transition: effects of a treatment-based and school-based
      program on emotionally troubled children and their adjustment to new placements.
AB  - This study compares the outcomes of two groups of 12-to-13 year olds who were in
      their last year at a day or five-day residential treatment center for seriously
      emotionally troubled children. One group was enrolled in a treatment-based
      program; the second group participated in a school-based program designed to ease
      the transition to new placements. Each group was evaluated when discharged from
      the center and 6 weeks after entering their new placements. Interviews with
      parents and teachers indicated that the school-based children scored
      significantly higher on six of eight indicators of adjustment than did children
      in the treatment-based program.

PMID- 9540244
TI  - A 29-year-old man with abnormal thyroid function tests.

PMID- 9540245
TI  - The herbal medicine boom: understanding what patients are taking.

PMID- 9540246
TI  - The diagnostic utility of c-ANCA in Wegener's granulomatosis.
AB  - Anti-neutrophil cytoplasmic antibodies with a cytoplasmic staining pattern (c
      ANCA) have been found to have a high degree of sensitivity and specificity for
      Wegener's granulomatosis. Nevertheless, despite the attraction of using this
      autoantibody as a diagnostic test, in almost all instances it should not be used
      in place of a biopsy to diagnose Wegener's granulomatosis.

PMID- 9540247
TI  - Commonly asked questions about premenstrual dysphoric disorder.
AB  - Although the etiology of premenstrual dysphoric disorder (PMDD), a severe form of
      premenstrual syndrome, is as yet unconfirmed, it is a biological condition that
      responds to biological therapies. With education, psychotherapy, and somatic and
      psychotropic treatment, women with PMDD can attain improved health and quality of
      life.

PMID- 9540248
TI  - Evaluating asymptomatic patients with mildly elevated liver enzymes.
AB  - Because elevated liver enzymes are found in 1% to 4% of asymptomatic persons,
      extensive evaluation of all abnormal tests would expose many patients to undue
      risks and medical costs. On the other hand, not evaluating minor elevations of
      liver enzymes could result in missing the early diagnosis of potentially
      treatable disorders. This review discusses likely causes of elevated
      aminotransferase, alkaline phosphatase, and gamma-glutamyl transferase levels and
      provides algorithms for evaluating abnormal liver enzyme values in apparently
      healthy patients in the primary care setting.

PMID- 9540249
TI  - What internists should know about amiodarone.
AB  - Amiodarone is a potent and versatile antiarrhythmic. Despite side effects
      involving the lungs, heart, thyroid, and other organs, it is effective in the
      treatment of refractory atrial and ventricular arrhythmias and it has unique
      safety in patients with coronary disease and left ventricular dysfunction. This
      review discusses the evolving indications for amiodarone and management of
      toxicities and drug interactions.

PMID- 9540250
TI  - Mental health and the Internet.

PMID- 9540251
TI  - The Internet: facilitating an international nursing culture for psychiatric
      nurses.

PMID- 9540252
TI  - Enhancement of basic computer skills. Evaluation of an intervention.
AB  - A series of self-paced tutorials was developed for use by graduate students on
      the assumption that acquisition of skills in accessing e-mail accounts, use of
      the World Wide Web, file-transfer protocols, Excel spreadsheet, and PowerPoint
      presentation software would help students succeed in their program of graduate
      studies. The postproject evaluation tool was sent to participants via e-mail, to
      reinforce the acquired skills and demonstrate the successful accomplishment of
      project objectives. Pre- and postevaluation data indicated an increase in self
      rated skill level after participation in the tutorial series. Analysis showed an
      overall mean gain score of 2.3 points, with pre- and posttutorial gain scores
      significantly increased for all topic areas.

PMID- 9540253
TI  - Using hypertext to facilitate nurse education.
AB  - The increased use of both multimedia and the World Wide Web for nurse education
      necessitates critical examination of the use of hypertext in nursing education.
      The use of hypertext and multimedia have the potential to revolutionize teaching
      and learning generally, and have a significant impact on nursing specifically.
      This article discusses hypertext use in nurse education and incorporates an
      examination of cognitive theories to identify specific hypertext design
      strategies customized for nursing user groups. Particular attention is directed
      to the application of cognitive flexibility theory to hypertext design for nurse
      education, highlighting the representation of both complex clinical situations
      and human physiology. The article concludes with a discussion of the potential
      uses of hypertext as a means of accessing information by nurses in clinical
      practice.

PMID- 9540254
TI  - Multimedia anatomy and physiology lectures for nursing students.
AB  - The use of the multimedia computer and projector can provide the lecturer who
      teaches anatomy and physiology to nursing students with a very powerful
      educational tool. The recent explosion in the number of Internet sites has
      resulted in a huge resource base of illustrations, photos, x-rays, and film
      clips, which are useful for anatomy and physiology multimedia presentations.
      These allow nursing students to be instructed in a clear, colorful, and dynamic
      fashion. This article shows how to put together anatomy and physiology multimedia
      presentations quickly and easily, and reviews some of the key sites on the
      Internet that provide resources suitable for lectures to nursing students.

PMID- 9540255
TI  - Guidelines for developing interactive multimedia. Applications in nurse
      education.
AB  - In an environment of increasing economic constraint, it is necessary for nurse
      educators to design and implement cost-effective teaching and learning
      strategies. Computer-based interactive multimedia applications in education have
      been touted as a cost- and time-effective method of providing a dynamic,
      information rich, learning environment. Given the profusion of this type of media
      in the general marketplace, an increasing number of educators are now wishing to
      develop specific computerized multimedia applications for use in nurse education.
      Accounts of a number of such developments exist in the literature. However, there
      is a dearth of literature outlining the processes involved in interactive
      multimedia production. It would, therefore, appear timely to address issues
      related to multimedia development. Based on the author's experiences, this
      article will offer a number of practical suggestions for the development of
      interactive multimedia applications in nursing education.

PMID- 9540256
TI  - Using e-mail in an undergraduate nursing course to increase critical thinking
      skills.
AB  - This article describes how e-mail was used in an undergraduate nursing course to
      increase contact between students and faculty. Students were required to respond
      to critical thinking questions using e-mail.

PMID- 9540257
TI  - [Beer drinkers have fewer myocardial infarcts. Moderate beer drinking lowers
      infarct incidence and total mortality].

PMID- 9540258
TI  - [Senile macular degeneration].
AB  - The most frequent cause of severe visual deficiency in old age is degeneration
      related neovascularization beneath the site of maximum visual discrimination. To
      date, the therapeutic possibilities are limited, but new methods of examination
      and treatment give reason for cautious optimism. In recent years, the condition
      has increased dramatically and, mild cases included, now affects some 20% of over
      70-year-olds. A basic knowledge of this degeneration should therefore be required
      of every family doctor.

PMID- 9540260
TI  - [Joy in driving is often clouded in the aged. Interview by Beatrice Wagner].

PMID- 9540259
TI  - [Current status of cataract surgery. Modern methods--internal medicine risk
      factors and contraindications].
AB  - Modern cataract surgery is characterized by minimal invasive techniques that have
      been introduced during the past decade. These include phacoemulsification,
      capsulorhexis, foldable intraocular lenses and small tunnel incisions. High
      success rates coupled with low complication rates have resulted in a change in
      indications--cataract surgery is no longer performed merely to prevent blindness,
      but also to improve vision in patients whose professional or private visual
      demands are compromised by the onset of lens opacification. To ensure that their
      cooperation with the ophthalmic surgeon results in optimal benefit to the
      patient, it is important for general practitioners and internists to be
      conversant with the risk factors and contraindications for cataract surgery.

PMID- 9540261
TI  - [Skin manifestations in Lyme borreliosis. 5: Rare skin manifestations of
      borreliosis].

PMID- 9540262
TI  - A possible solution to the cost explosion of the emergency department.
AB  - Once considered a source of care for major injuries and life-threatening medical
      conditions, the emergency department has become part primary care physician and
      part social worker to many Americans. This article looks at the problem of
      emergency room overutilization and poses some solutions to stem the rising cost
      of urgent care.

PMID- 9540263
TI  - Seizures in east-bound visitors to Hawaii.
AB  - Anecdotal observations by emergency physicians at Straub Clinic and Hospital
      suggest that first-time seizures are common in Japanese tourists visiting Hawaii.
      Because such patients seemed to present in the evening of their day of arrival,
      some physicians have attributed these seizures to sleep deprivation based
      primarily upon clinical impressions. However, there has been no previous review
      of these cases to confirm the impression that these seizures have a relatively
      benign cause. This retrospective study aims to identify the role of sleep
      deprivation as a potential factor in seizures within this population.

PMID- 9540265
TI  - Cutaneous malignant lymphomas.

PMID- 9540264
TI  - Prenatal care utilization in Hawaii: did it improve during the last 16 years?
AB  - This paper examines the utilization of prenatal care in Hawaii from 1979 to 1994
      to determine if early and adequate utilization of prenatal care has changed
      during this period. Birth certificates of single live born infants of resident
      women were the source of data for the study. During the study period, the
      proportion of women receiving prenatal care in the first trimester increased by
      nearly 5 percent but was still below the national and state Year 2000 health
      objective of 90 percent. Notwithstanding this improvement, the percentage of
      women who did not receive the recommended number of visits in spite of starting
      care early significantly increased. The overall proportion of women with
      'intensive' prenatal care use markedly increased (134.7%). The proportion of
      women with 'inadequate' care use declined (10.3%), although the proportion of
      women with 'no care' use doubled. Complete reporting of use of care through birth
      certificates markedly deteriorated. The findings of this study indicate the need
      for changes in the targeting and provision of counseling and education on the
      part of health care providers. Public health leaders, policy makers, health care
      providers, and advocacy groups need to collectively review programmatic
      directions with an aim toward the development of innovative approaches to address
      the emerging health needs of mothers and infants in the state.

PMID- 9540266
TI  - Gene therapy in the treatment of autoimmune disease.

PMID- 9540267
TI  - CD5 and other superantigens as 'ticklers' of the B-cell receptor.

PMID- 9540268
TI  - Much ado about minor histocompatibility antigens.

PMID- 9540269
TI  - Give us this day our daily germs.
AB  - Modern vaccinations, fear of germs and obsession with hygiene are depriving the
      immune system of the information input upon which it is dependent. This fails to
      maintain the correct cytokine balance and fine-tune T-cell regulation, and may
      lead to increased incidences of allergies and autoimmune diseases. If humans
      continue to deprive their immune systems of the input to which evolution has
      adapted it, it may be necessary to devise ways of replacing it artificially.

PMID- 9540270
TI  - The possible role of bacterial superantigens in the pathogenesis of autoimmune
      disorders.
AB  - The ability of superantigens (SAgs) to activate the immune system suggests that
      they may play a role in the course of autoimmune disorders. Here, Joel
      Schiffenbauer and colleagues review evidence from animal models of autoimmunity,
      as well as human data that support this hypothesis, and propose a model for SAg
      involvement in autoimmune disorders.

PMID- 9540271
TI  - Fas-FasL interactions: a common pathogenetic mechanism in organ-specific
      autoimmunity.
AB  - Organ-specific autoimmunity is characterized by the accelerated loss of selected
      cell types, resulting in specific tissue destruction and disease. The role of
      different genetic or environmental factors in initiating the autoimmune
      reactivity is still unclear. However, novel mechanisms responsible for tissue
      destruction have recently been revealed. Here, Ruggero De Maria and Roberto Testi
      propose that Fas ligand may represent a common weapon during the destructive
      phase of organ-specific autoimmunity.

PMID- 9540272
TI  - Towards development of T-cell vaccines.
AB  - Recent studies on the recognition of antigens by CD4+ and CD8+ T cells have
      revealed new ways of preparing efficient T-cell vaccines. Here, Constantin Bona
      and colleagues discuss several approaches for the development of T-cell vaccines,
      with applications ranging from the induction of protective immunity against
      intracellular parasites to the development of therapeutic agents against
      autoimmune disorders, allergic diseases and cancer.

PMID- 9540273
TI  - Allergic and autoimmune reactions to xenobiotics: how do they arise?
AB  - Induction of allergic and autoimmune reactions by drugs and other chemicals
      constitutes a major public health problem. Elucidation of the underlying
      mechanisms might help improve diagnostic tools and therapeutic approaches. Here,
      Peter Griem and colleagues focus on several aspects of neoantigen formation by
      xenobiotics: metabolism of xenobiotics into reactive, haptenic metabolites;
      polymorphisms of metabolizing enzymes; induction of costimulatory signals; and
      sensitization of T cells.

PMID- 9540274
TI  - B-cell help by Tc2 cells.

PMID- 9540276
TI  - Migration of naive and memory T cells in vivo.

PMID- 9540275
TI  - T-cell modulation in decidua.

PMID- 9540277
TI  - The thymic extracellular matrix in genetically engineered mice.

PMID- 9540278
TI  - Experimental autoimmune uveitis as animal model for human posterior uveitis.
AB  - Uveitis is an intraocular inflammatory disease that mostly affects children and
      young adults. It is one of the major causes of blindness in young individuals in
      India and the world. It is responsible for about 10 per cent of total visual
      impairment. Unfortunately, etiological diagnosis is not evident in a majority of
      these patients. It is generally felt that autoimmune mechanism may be involved in
      so called 'idiopathic' cases which has led to search for the putative
      autoantigens in experimental animal models. It has been demonstrated that
      experimental autoimmune uveitis (EAU) can be elicited against several retinal
      proteins in rats, mice and sub-human primates. These include the S-antigen, a
      major protein on retinal photoreceptor cell, interphotoreceptor retinoid binding
      protein (IRBP) and several others. There are many similarities between clinical
      entities and the EAU, but the EAU differs from the clinical conditions in being
      self-limited, and requiring complete Freund's adjuvant for induction of the
      disease. The disease can be induced only in susceptible strains. Nevertheless,
      use of the EAU model has allowed for identification of disease causing epitopes
      of antigens and evaluation of disease modifying strategies which could be applied
      in clinical situations. There has been significant progress in this field, but
      still a lot more is required to be learnt to translate it into clinical practice.

PMID- 9540279
TI  - Study of Pseudomonas aeruginosa causing ventilator associated pneumonia.
AB  - Ps. aeruginosa is a frequent and prominent cause of nosocomial pneumonia
      especially in persons on assisted ventilation in the intensive care units. In a
      year long surveillance of ventilator associated pneumonia (VAP) we isolated 42
      strains from broncho alveolar lavage samples collected and processed from 102
      patients. By pyocin typing 40 of the 42 strains could be typed into 39 types but
      this designation changed each time the test was repeated. SDS-PAGE analysis of
      the whole cell proteins grouped the 42 strains of Ps. aeruginosa into 20 groups.
      After ribotyping, using an 18 mer DIG labelled oligonucleotide to the conserved
      region of 16S rRNA gene, the strains were designated into 18 types. The major
      type contained 8 isolates, but there was no clustering of isolates, indicating
      that each infecting strain was acquired separately and not from a common source.
      It would, therefore, appear that cross infection with a single clone was not the
      predominant mode of Ps. aeruginosa infection causing VAP in our ICU.

PMID- 9540280
TI  - Bioluminescence assay of adenosine triphosphate in drug susceptibility testing of
      Mycobacterium tuberculosis.
AB  - Twenty three clinical isolates M. tuberculosis and the reference strain, M.
      tuberculosis H37Rv were tested for their susceptibility to trifluoperazine (TFP)
      by the standard broth dilution method and the bioluminescence assay. The results
      showed that in 15 of the 23 isolates, the minimal inhibitory concentration (MIC)
      was identical in both the methods and in the remaining 8 isolates the difference
      in the MIC values between the methods, was less than two fold and was not
      significant. The findings suggest that the measurement of adenosine triphosphate
      (ATP) by bioluminescence assay can be employed as an alternative method for the
      rapid screening of clinical isolates for their susceptibility to anti
      mycobacterial agents.

PMID- 9540281
TI  - A prospective study on the incidence of hepatitis B & C infections amongst
      patients with lymphoproliferative disorders.
AB  - Fifty one patients with acute lymphoblastic leukaemia (ALL) and non-Hodgkins
      lymphoma (NHL) undergoing chemotherapy were studied prospectively to determine
      the incidence, aetiology and natural course of hepatitis. Of 51 patients (31 NHL
      and 20 ALL), 22 developed hepatitis. Hepatitis B (IgM anti HBc positive) was the
      cause in 11 patients (50%), hepatitis C in 4 patients, and septicaemia and
      cytotoxic drugs in 3 patients each. Malignant infiltration of the liver was the
      cause in the remaining 1 patient. Hepatitis was predominantly (75%) anicteric.
      Mean duration of hepatitis was 21 days. Of 51 patients, 21 acquired hepatitis B
      and/or C virus infection. They had received 6.4 (+/- 3.4) units of packed red
      cells and 5.3 (+/- 11) units of platelet concentrate as compared to 3.4 (+/- 4.8)
      units of red cells and 5.3 (+/- 12.1) units of platelet concentrate received by
      those who did not acquire virus infection (P < 0.05 for packed red cells). Only
      transient stoppage of chemotherapy was necessary following development of
      hepatitis and most of the patients who developed hepatitis could complete their
      chemotherapy schedule. None of the patients who developed viral B or C infection
      cleared the infection. We conclude that there was a high incidence of hepatitis B
      and C infection amongst patients with lymphoproliferative disorders with an
      increased carrier rate. Transfusion was a major risk factor for such infections.

PMID- 9540282
TI  - Partial sequence analysis of a Plasmodium vivax cation transporting ATPase gene
      homologue & a putative pseudohomologue.
AB  - Molecular characterization of P. vivax is essential to develop suitable
      antimalarial drugs and vaccines. We describe here isolation and sequence analysis
      of a partial cDNA of a calcium ATPase as well as a putative pseudogene from this
      parasite. The immunoscreening of lambda gtll- P. vivax DNA library with patients
      serum has earlier resulted in the isolation of several seroreactive clones
      including Pv14. This clone contains a 299 bp insert having 18 amino acids (aa)
      reading frame fused with beta galactosidase. A larger fragment of approximately
      15 kb was isolated from the EMBL3 library for Pv14 but it had only 2 extra aa in
      its reading frame. The far upstream region of Pv14 revealed a 101aa long putative
      open reading frame (ORF) showing homology to a variety of calcium ATPases in the
      M8 and M9 transmembrane region. But in the absence of a transcript in the
      parasite could indicate that it represents a pseudogene. However, the real gene
      for calcium ATPase in P. vivax was detected by RT-PCR using degenerate primers,
      designed from the conserved sequences of energy transduction and phosphorylation
      domains. The amplified cDNA-PCR product of 550 bp was cloned and sequenced which
      showed a significant aa homology to the calcium ATPase4 of P. falciparum. The
      present study, therefore, establishes the existence of calcium ion pumps in P.
      vivax which will be useful in drug development.

PMID- 9540283
TI  - Prevalence of fungal species in patients with funguria.
AB  - Fungal isolates recovered from urine samples of high risk group of symptomatic
      patients (n = 446) over a period of 12 months were identified and prevalence of
      different species was determined. Four Candida species viz., Candida albicans, C.
      tropicalis, C. krusei and C. pseudotropicalis accounted for 84 per cent (205) of
      the yeast species isolated. Seven different species of Candida were recovered,
      besides 5.3 per cent (13) unidentified yeast. Most of the yeasts were identified
      within 48 h. Funguria poses a management problem in seriously ill patients.

PMID- 9540284
TI  - Analysis of meiotic segregation in human nondecondensed interphase spermatozoa by
      triple colour rapid direct fluorescent in situ hybridization.
AB  - Meiotic segregation of chromosomes X,Y and 1 was analyzed by triple colour rapid
      fluorescent in situ hybridization (FISH) with directly labelled probes on 4506
      non-decondensed and non-cleaned interphase spermatozoa from four healthy male
      donors to test the possibility of rapid sperm FISH by omitting the conventional
      sperm decondensation and cleaning steps. Only 0.15 per cent of sperms were
      without any signals which suggested high hybridization success. An abnormal
      number of signals was seen in 1.6 per cent of sperms. Chromosome specific as well
      as donor specific segregation error was seen similar to previous reports. There
      was a wide variation in the ratio of normal X and Y bearing sperm from donor to
      donor. This study indicated that for segregation studies sperm FISH can be
      carried out in three hours with directly labelled probes without the steps for
      separation of sperm from somatic cells (cleaning), sperm swelling and sperm DNA
      decondensation.

PMID- 9540285
TI  - Sequelae of early undernutrition on reaction time of rural children at 11-14
      years.
AB  - 85 undernourished rural school children at 11-14 yr of age were randomly selected
      on the basis of their nutritional status during first five years of life for
      assessment of reaction time (RT). Audio-visual RT apparatus and electromyograph
      were used for the study. Early life undernourished children had prolonged RT as
      compared to their matched control maintaining normal nutrition status in first
      five years of life. The total, premotor and motor RT for audio as well as visual
      stimuli were affected in these undernourished children. The RT increased with
      severity of current undernutrition; those achieving normal nutritional status at
      this age continued to have prolonged RT. The study suggests that the early life
      undernutrition affects perceptual abilities, information processing and
      analytical capabilities.

PMID- 9540286
TI  - Metabolic responses to repeated infusions of identical doses of norepinephrine in
      chronically energy deficient human subjects.
AB  - The physiological effects of three 30 min infusions of identical doses of
      norepinephrine (0.15 microgram/kg FFM/min) separated by 60 min intervals were
      assessed in well nourished (WN; n = 6) and chronically energy deficient (CED; n =
      6) subjects. Each subject also underwent control, vehicle infusions with 0.9 per
      cent saline on a separate day. Oxygen consumption (VO2) was significantly higher
      during the third infusion of NE as compared to the first in both groups. This
      increment in VO2 occurred despite similar plasma peak NE levels in both
      infusions. Increments in plasma glucose and free fatty acids were also similar
      during the first and third infusions. The study demonstrates that thermogenic
      potentiation which we had earlier demonstrated in WN subjects, occurs in CED
      subjects as well. Thermogenic potentiation is not associated with altered plasma
      NE kinetics or mobilisation of substrates.

PMID- 9540287
TI  - Training tomorrow's doctors: the clinical skills laboratory.

PMID- 9540288
TI  - Cancer metastasis: biological and clinical aspects.
AB  - The main cause of morbidity and mortality in cancer is the formation of distant
      metastases. While alterations in c-oncogenes, tumour suppressor genes and DNA
      repair enzymes are the key molecules involved in carcinogenesis, increased
      expression of proteases, motility factors and altered expression of adhesion
      molecules are causally involved in metastasis. The proteases mediating metastasis
      include urokinase plasminogen activator, cathepsin B, D and L and various matrix
      metalloproteinases. Certain proteases involved in metastasis (e.g., urokinase
      plasminogen activator) have been shown to be strong and independent prognostic
      markers for a variety of cancers. Finally, molecules involved in cancer spread
      are potential targets for new forms of anti-metastatic therapies.

PMID- 9540289
TI  - Enterocutaneous fistula: a reconstructive dilemma.
AB  - Surgical repair of enterocutaneous fistulae in Crohn's disease may result in
      large skin defects of the anterior abdominal wall. We present a case in which a
      large defect was managed with reconstruction using a pedicled rectus abdominis
      myocutaneous flap in a single procedure. The case highlights the technical
      challenge of such a case and the value of a joint surgical approach between
      plastic and colorectal services.

PMID- 9540291
TI  - Essential pre-conceptual measures for the female partner before commencing an in
      vitro fertilisation programme.
AB  - Two hundred and eighty-one women were checked for the presence of specific pre
      conceptual data and their medico-legal implications prior to commencing an in
      vitro fertilisation (IVF) programme. In only 9.6 per cent were the results of a
      recent rubella test available in the patients referral notes. Fifty-four per cent
      were then tested in the unit. Two per cent were found to be not immune. Thirty
      six per cent of women needed a cervical smear prior to commencing therapy. No
      such test had been undertaken previously in 6.7 per cent and 12.7 per cent had
      abnormal test results. Pre-conceptual intake of folic acid is considered an
      important preventative measure. The patient uptake rose from 15 per cent to 97
      per cent following specific advice.

PMID- 9540290
TI  - Symptoms of oesophageal reflux are more common following laparoscopic
      cholecystectomy than in a control population.
AB  - Previous studies have shown that up to 40 per cent of patients have symptoms
      after cholecystectomy or laparoscopic cholecystectomy (LC). There are concerns,
      however, that these symptoms reflect those of the general population and are not
      a specific post-operative phenomenon. Abdominal symptoms of 212 patients
      following LC were compared to a healthy acalculous control population (n = 62).
      Patients and controls were assessed by questionnaire. Age and sex profiles were
      similar in both groups. There was no significant difference in the incidence of
      abdominal pain, bloating or nausea between the 2 groups. Frequent heartburn was a
      symptom in 19.3 per cent of patients following LC as compared to 3.2 per cent of
      control patients (p = 0.004, chi-squared 9.39, 1 d.f.). Furthermore 11.3 per cent
      of post-operative patients complained of dysphagia versus 6.4 per cent of the
      control group (p = 0.08, chi-squared 1.245, 1 d.f.). One hundred and twenty (57.1
      per cent) patients judged their operation to be a complete success, while 9 (4.3
      per cent) were dissatisfied. Five of the latter group cited frequent heartburn as
      the cause of their dissatisfaction. We conclude that abdominal pain, bloating and
      nausea occur as frequently in the general population as in patients following LC.
      Patients are more likely to suffer from heartburn and dysphagia following LC than
      a normal population supporting a link between cholecystectomy and lower
      oesophageal dysfunction.

PMID- 9540292
TI  - Effect of accommodation on intraocular pressure in glaucomatous eyes.

PMID- 9540293
TI  - Bacterial toxin-induced pulmonary epithelial cytotoxicity and the protective
      effect of dibutyryl-cAMP.
AB  - Bacterial infection is the most common cause of the adult respiratory distress
      syndrome which, in turn is associated with endothelial capillary permeability and
      alveolar oedema. Previously, we have demonstrated the direct cytotoxicity of the
      bacterial toxins Pseudomonas aeruginosa exotoxin A (Exo A) and Salmonella
      enteritidis lipopolysaccharide (LPS) on pulmonary endothelial cells. The purpose
      of this study was to investigate the effect of Exo A and LPS on pulmonary
      epithelial cells in vitro. We also tested the protective effect of dibutyryl
      cyclic adenosine monophosphate (db-cAMP) on Exo A-induced cytotoxicity. In
      cultured rat alveolar epithelial cells (RAEC) Exo A caused cytotoxicity as
      measured by 51Cr release from these cells. LPS did not injure RAEC's.
      Pretreatment of RAEC with db-cAMP (1 mM) attenuated Exo A induced cytotoxicity.
      We conclude that (1) Exo A directly injures epithelial lung cells and may
      contribute to lung injury in cases of bacterial infection; (2) db-cAMP protects
      alveolar epithelial cells against Exo A-induced cytotoxicity and (3) alveolar
      epithelial cells in this model are resistant to LPS induced injury.

PMID- 9540294
TI  - The effect of fatigue, sleep deprivation and onerous working hours on the
      physical and mental wellbeing of pre-registration house officers.
AB  - The potential deleterious effects of doctors' long and arduous shifts have
      received relatively scant attention. This study addressed the effect of a 32 h on
      call shift on 16 pre-registration medical house officers in St. James's Hospital,
      Dublin. We assessed 5 psychological parameters (Tension-Anxiety, Depression
      Dejection, Vigour-Activity, Fatigue-Inertia and Confusion-Bewilderment) as well
      as 5 simple tests of alertness and concentration both pre- and post-call. The
      doctors were randomly assigned to be tested either pre- or post-call. On average
      the doctors got 4.5 hours sleep during a 32 h shift. This long shift had an
      adverse effect on all the psychological parameters (p < 0.05) except Depression
      Dejection. The total mood disturbance score, which has been shown to correlate
      well with general psychological well-being, deteriorated significantly after the
      32 h shift, p < 0.005. Two of the simple tests of alertness and concentration
      (Trail-making test and Stroop Color-Word test) also showed a significant fall-off
      in performance with sleep deprivation, p < 0.05, although the remaining tests
      (Delayed Story Recall, Critical Flicker Fusion and Three Minute Grammatical
      Reasoning Test) were not significantly impaired by the 32 h shift. This study
      shows that prolonged periods of duty without sleep adversely affect junior
      doctors, both in their psychological well-being and in their ability to carry out
      simple tasks.

PMID- 9540295
TI  - Perianal hidradenoma papilliferum occurring in a male: a case report.
AB  - Hidradenoma papilliferum is a rare apocrine gland tumour, described only once
      previously in a male. We present the second such case.

PMID- 9540297
TI  - Stroke: non-motor sequelae, medical co-morbidity and patterns of intervention
      after referral to a special interest service.
AB  - Stroke poses a considerable financial burden on the health services as well as
      contributing to enormous personal suffering. A study was undertaken in 100
      patients over 65 years old in a geriatric unit. Neuro-radiology confirmed
      cerebral infarcts in 91 and 89 per cent had additional neuro-medical problems.
      Specific sequelae of stroke occurred in 53 per cent of which 21 per cent related
      to dysphagia. Among various treatments 61 per cent were referred for
      physiotherapy and occupational and speech/language therapy. Knowledge of the
      nature and timing of complications is important in planning stroke services and
      the input of early medical specialist assessment has been shown to influence
      mortality and rehabilitation outcome.

PMID- 9540296
TI  - Perinatal transmission of HIV and diagnosis of HIV infection in infants: a
      review.
AB  - Paediatric HIV infection has become a major burden on families, communities and
      health services worldwide. The vast majority of children now acquire HIV as a
      result of mother to infant (vertical) transmission. Recent major advances have
      occurred following the greater understanding of the risk factors for perinatal
      transmission and the role of antiretroviral therapy in preventing transmission.
      Now that interruption of vertical transmission is possible, early identification
      of HIV-infected pregnant women is critical. As of June 1997, HIV infection has
      been diagnosed in 37 children under 15 yrs of age in the Republic of Ireland; 32
      as a result of maternal to infant transmission. The exact timing of HIV
      transmission during pregnancy is unclear but it is estimated that 60-70 per cent
      of infants may be infected at the time of delivery with approximately 30 per cent
      infected earlier in gestation. Vertical transmission rates vary from 15-40 per
      cent in different global areas. Antenatal and perinatal zidovudine treatment can
      reduce this rate by 60-70 per cent. Risk factors for the vertical transmission of
      HIV-1 are multifactorial. These factors include maternal disease status, in
      particular maternal viral load, route of delivery, duration of membrane rupture,
      presence of obstetric complications and infant feeding practices. Definitive
      diagnosis of HIV infection in infancy has been difficult in the past. Direct
      viral detection methods now allow the reliable diagnosis of HIV infection in the
      first few months of life. The most effective intervention to reduce perinatal HIV
      infection will be the better identification of HIV positive pregnant women with
      the subsequent introduction of measures to interrupt vertical transmission of
      HIV.

PMID- 9540298
TI  - Oesophageal motility and digestion of cream liqueurs in combination with common
      alcohol mixers.
AB  - When acidic mixers are added to cream liqueur curdling occurs. Oesophageal
      motility was studied in normal volunteers during ingestion of this mixture and
      the effect of combining with gastric juice was assessed in a simulated
      physiological environment. Twenty-four h ambulatory manometry and pH (n = 22) and
      gastric studies (n = 7) were carried out. There was no detrimental effect on
      oesophageal motility. The precipitation is rapidly broken down by the digestive
      process in the stomach.

PMID- 9540299
TI  - Helicobacter pylori does not play a role in the aetiology of acute appendicitis.
AB  - The aetiology of acute appendicitis remains uncertain. H. pylori is viable
      outside the gastroduodenum, however its pathological role outside this area has
      not been fully investigated. Ten consecutive patients with a histological
      diagnosis of acute appendicitis were investigated for H. pylori status by
      serology, and by culture, histology, and polymerase chain reaction (PCR) analysis
      of the appendiceal specimens. One patient had positive serology for H. pylori,
      however PCR analysis was negative. Culture failed to reveal H. pylori colonies.
      Histology in 5 cases did reveal organisms with a morphological appearance of H.
      pylori, but PCR analysis confirmed that H. pylori was not present. Using a
      variety of methods, with PCR acting as the 'gold standard', we have shown that H.
      pylori is not associated with acute appendicitis.

PMID- 9540300
TI  - Colonic pseudo-obstruction following acute pancreatitis.
AB  - The purpose of this case presentation is to illustrate the rate association
      between acute pancreatitis and colonic pseudo-obstruction and to highlight the
      difficulties of assessing intestinal motility in a defunctioned segment of bowel
      prior to closure of a defunctioning stoma.

PMID- 9540302
TI  - Oral health and dental status have improved dramatically on a worldwide basis.

PMID- 9540301
TI  - Free radicals in inflammatory neurological disease: increased lipid peroxidation
      and haptoglobin levels in Guillain Barre syndrome.
AB  - Oxidative damage in three inflammatory neurological disorders; Guillain Barre
      syndrome (GBS), multiple sclerosis and aseptic meningitis, were assessed by
      measuring the peroxidation of lipids in body fluids. The results were compared to
      a control group consisting of patients with either migraine, chronic/tension
      headaches, benign intracranial hypertension or psychological disorders.
      Antioxidant status was assessed by the measurement of the extracellular proteins,
      haptoglobin, albumin, caeruloplasmin and transferrin. The results of the study
      suggested that firstly, haptoglobin levels might be a useful, easily obtainable
      marker to aid the diagnosis of GBS. Secondly, free radical damage may be
      implicated in the pathology of GBS and therefore appropriate free radical
      scavenging might have beneficial effects.

PMID- 9540303
TI  - Occlusal caries diagnosis: an in vitro histological validation of the Electronic
      Caries Monitor (ECM) and other methods.
AB  - OBJECTIVES: The aim of this in vitro study was to validate the use of the
      Electronic Caries Monitor (ECM) for the detection of enamel and dentinal caries
      on the occlusal surfaces of posterior teeth, and to compare it with visual
      examination, fibre-optic transillumination, conventional and digital bitewing
      radiography. METHODS: One-hundred and three extracted posterior permanent teeth
      with no apparent occlusal cavitation were selected and examined using each
      system. Thirty teeth were re-examined with each system to assess repeatability.
      Each tooth was then serially sectioned and examined histologically for occlusal
      caries. RESULTS: The occlusal surfaces of 25 teeth had caries in enamel and 37
      had dentinal carious lesions. The sensitivity and specificity of the ECM were
      0.78 and 0.80 for the diagnosis of occlusal dentinal lesions (cut-off = 0.391)
      and 0.65 and 0.73 for enamel lesions (cut-off = 0.501). The weighted kappa value
      for repeatability of the ECM was 0.68. Of the other diagnostic systems, visual
      examination provided the best combination of sensitivity and specificity, 0.24
      and 0.97 for dentinal caries and 0.60 and 0.73 for enamel caries, respectively.
      CONCLUSION: The ECM was the most accurate diagnostic tool for the in vitro
      diagnosis of early, non-cavitated occlusal lesions on posterior teeth.

PMID- 9540304
TI  - A comparison of two histological validating techniques for occlusal caries.
AB  - Validation of a diagnostic technique is important to establish whether it
      actually measures what it is purported to measure. However, the accuracy of the
      validation technique per se can influence the apparent accuracy of the diagnostic
      technique. OBJECTIVES: The aim of this study was to describe two alternative
      histological validating techniques for occlusal caries and to compare
      quantitative depth measurements of carious lesions taken using each method.
      METHODS: Thirty sections (mean thickness 0.67 mm) were cut to include two to four
      discrete sites in 10 freshly extracted teeth. The first histological validating
      technique used a microfocal X-ray unit to produce magnified high definition
      radiographic images of the sections or 'macroradiographs'. An image analysis
      system was used to make quantitative measurements of the lesions (if present)
      with respect to the enamel-dentine junction (EDJ). The second validating
      technique used a confocal microscope to image beneath the cut surface of the
      section. Quantitative measurements were taken from the fluorescence images of
      both sides of each section and a mean depth measurement calculated. RESULTS:
      Complete agreement was found between the two validating techniques for the
      subjective interpretation of the presence and extent of caries. A strong positive
      relationship was found between the two histological validating techniques for
      depth measurements made of dentine caries from the EDJ (r = 0.93, P < 0.001).
      Depth measurements made from the macroradiographs were greater than from the
      confocal fluorescence images (mean difference = 0.41 mm). CONCLUSIONS: Both
      validating techniques enable the identification of sound sites, those with enamel
      caries and dentine caries. However, quantitative assessments made with each
      technique could result in disagreement.

PMID- 9540305
TI  - Measurement of prostaglandin E2 and leukotriene B4 in the gingival crevicular
      fluid.
AB  - The arachidonic acid metabolites prostaglandin E2 (PGE2) and leukotriene B4
      (LTB4) are inflammatory mediators which are likely to be involved in the
      pathogenesis of periodontal disease. PGE2 mediates vasodilatation, increases
      vascular permeability, enhances pain perception by bradykinin and histamine,
      alters connective tissue metabolism and enhances osteoclastic bone resorption.
      LTB4 causes the accumulation of inflammatory cells in the inflamed sites, and
      degranulation of polymorphonuclear leukocytes. OBJECTIVE: To measure gingival
      crevicular fluid (GCF) levels of PGE2, LTB4 and periodontal health. METHODS: The
      periodontal condition of 24 subjects was evaluated on the basis of plaque index,
      gingival index, probing depth, and attachment level. GCF samples were collected
      from one or two site(s) of each sextant per subject and the volume was measured
      using Periotron 6000. Samples were then assayed for PGE2 and LTB4 using a
      competitive enzyme immunoassay. Mean PGE2 and LTB4 levels were determined for
      each subject and group means compared. RESULTS: Significant differences in the
      levels of PGE2 and LTB4 were found between patients with periodontitis, and non
      periodontitis individuals (P < 0.001). The PGE2/LTB4 levels were positively
      correlated with the clinical parameters (P < 0.01) and reduced markedly after
      phase 1 of the periodontal treatment (P < 0.01). The total amount and
      concentration (ng ml-1) of LTB4 was positively correlated with the gingival index
      (P < 0.01). CONCLUSIONS: These results indicate that the levels of PGE2
      correlated with the severity of the periodontal status, and the levels of LTB4
      correlated with gingival inflammation. Thus, our data suggest that the total
      amounts of PGE2/LTB4 may be good indicators for periodontal inflammation.

PMID- 9540306
TI  - Correlation between inclination of occlusal plane and masticatory movement.
AB  - OBJECTIVES: The purpose of this study was to investigate the relationship between
      the inclination of the occlusal plane and masticatory movement. METHODS:
      Masticatory movements of 41 young adults were measured using the three
      dimensional Mandibular Movement Analyzing System. The inclination of the occlusal
      plane was measured in the sagittal plane using a three-dimensional digitizer.
      RESULTS: In the sagittal plane, the masticatory closing path and the occlusal
      plane were consistent in maintaining a perpendicular relation with each other
      regardless of the inter-individual variation of the inclination of the occlusal
      plane. Subjects with an anteriorly inclined occlusal plane showed a vertical
      closing path, and subjects with a posteriorly inclined occlusal plane showed a
      flat closing path in the frontal plane. These characteristics were explained by
      the variation of the timing on the balancing-side condylar return correlated with
      the inclination of the occlusal plane. CONCLUSIONS: There is a significant
      correlation between the inclination of the occlusal plane and the direction of
      the closing path during mastication.

PMID- 9540307
TI  - The electrical resistance of enamel-dentine cylinders. Influence of NaCl content
      in storage solutions.
AB  - OBJECTIVES: To investigate the influence of different electrolyte concentrations
      on the electrical resistance of sound human enamel-dentine cylinders in vitro.
      METHODS: Forty cylinders of 3-mm diameter and 2-mm length were drilled from 40
      extracted caries-free third molar teeth. For ease of handling the samples were
      fixed in Perspex discs by means of a cyanoacrylate-adhesive. An a.c. source
      (frequency 500 Hz, amplitude 1 microA) with a high internal resistance was
      applied. Only Ohm's resistance was measured. The resistance measurements on the
      samples were made after storage in distilled water, 0.16 mM NaCl, 1.6 mM NaCl and
      16 mM NaCl and 160 mM NaCl for 24 h. RESULTS: The mean resistance values were
      2026 +/- 152, 1835 +/- 178, 1605 +/- 364, 483 +/- 265 and 60 +/- 33 k omega,
      respectively. All values were statistically significantly different (Wilcoxon
      test; P < 0.0001). CONCLUSION: It is concluded that the choice of electrolyte
      solution influences the resistance values of the enamel-dentine samples. This
      effect should be taken into account when measuring electrical resistances in vivo
      and in vitro.

PMID- 9540308
TI  - Spectroscopic studies of three osseointegrated implants.
AB  - OBJECTIVES: The purpose of this study was to investigate the surface
      characteristics of titanium implants. METHODS: The chemical state of the surfaces
      of three types of osseointegrated titanium implant, Branemark (Nobelpharma,
      Goteborg, Sweden), IMZ (Friatec, Mannheim, Germany) and ITI-Bonefit (Straumann,
      Waldenburg, Switzerland), were analysed by Auger electron spectroscopy (AES) and
      X-ray photoelectron spectroscopy (XPS). RESULTS: The outermost layers of the
      implants investigated were speculated to be TiO2. In the Branemark implants pure
      titanium was found under the TiO2 layer. By contrast, in the IMZ and ITI-Bonefit
      implants which are titanium plasma spray coated, oxygen atoms were observed at
      considerable depths by AES, and the material under the TiO2 layer showed a
      chemical shift by XPS. Furthermore, shifted peaks were not of pure titanium or of
      titanium oxide. CONCLUSION: The three titanium implants investigated were found
      to have different surface characteristics when examined by spectroscopy. As these
      implants show similar osseointegration it is suggested that they may be found to
      interact differently with vital bone.

PMID- 9540309
TI  - Qualitative assessment of stress distribution during insertion of endodontic
      posts in photoelastic material.
AB  - OBJECTIVES: The purpose of this study was to investigate the stress patterns
      associated with prefabricated endodontic posts during the various stages of
      insertion according to a number of design characteristics. METHODS: In a
      photoelastic material with elastic properties comparable to dentin, analyses were
      performed of the overall stress patterns with polarized light revealing
      substantial differences in stresses generated by the various posts. The effects
      of variations in design for certain configurations of the posts were also
      assessed. RESULTS: One geometric feature was the retentive thread of the post.
      The stress patterns within the photoelastic material revealed a homogeneous
      distribution of stress along the entire length of the thread, and more threads
      induced additional stress. The stress recorded with a vent when the pitch of the
      thread was 0.8-1.0 mm was classified as minimal-to-mild stress. Another geometric
      feature considered was the head (coronal extension) of the post. Minimal stress
      was recorded in the material in contact with the head and the apical end of the
      post when the contact surface of head was more than 3 mm2. CONCLUSIONS: This
      study suggests that during insertion of threaded posts the least stress occurs
      when the head contact surface is sufficient (> or = 3 mm2). A thread with a pitch
      of 0.8-1.0 mm is most desirable in stress reduction. The number of windings
      should also be limited (less than six windings) as samples with a substantial
      number of windings (N = 13 or 30) produce severe stress.

PMID- 9540310
TI  - In vitro caries inhibition by polyacid-modified composite resins ('compomers').
AB  - OBJECTIVES: The aim of this study was to compare the in-vitro caries inhibition
      of two polyacid-modified composite resins (PMCRs). METHODS: Three standardized
      class V cavities were prepared in eight extracted human molar teeth. Two of these
      cavities in each tooth were restored with Compoglass and Dyract according to
      manufacturers' guidelines. A conventional glass-ionomer cement restoration
      (Chemfil II) was placed in the third cavity in each tooth as a control. The teeth
      were submerged in an acid gel (lactic acid, gelatin, thymol, pH 4.5) for 28 days
      and then resin embedded. Ground sections were examined at x 160 magnification for
      enamel surface lesion depth, dentine surface lesion depth, wall lesions and
      evidence of caries inhibition. RESULTS: There was no significant difference
      between the depths of enamel or dentine surface lesions between the two compomer
      and conventional glass-ionomer materials. However, both PMCRs exhibited greater
      wall lesions than the conventional glass-ionomer material indicating less caries
      inhibition. CONCLUSIONS: These results suggest that PMCRs provide less caries
      inhibition than glass-ionomer cements.

PMID- 9540312
TI  - Relation between water content in acetone/alcohol-based primer and interfacial
      ultrastructure.
AB  - OBJECTIVES: This study investigated the ultrastructure of the resin-dentine
      interface when a two-bottle primer system containing NTG-GMA (N(p-tolyl)glycine
      glycidyl methacrylate) and BPDM (biphenyl dimethacrylate) was used with different
      concentrations of water as a part of the primer solvent: (I) an experimental
      version of All-Bond 2 with no water in primer A; (II) a commercial version of All
      Bond 2 (Bisco, Itasca, IL, USA) with 5% water in primer A; and (III) a former
      version of All-Bond 2 with 17% water in primer A. METHODS: Thirty-six 1-mm thick
      dentine discs prepared from third permanent molar teeth were each conditioned
      with 10% phosphoric acid for 20 s and rinsed for 20 s. They were randomly divided
      into three groups: Group A, conditioned dentine surface air-dried for 30 s; Group
      B, air-dried for 3 s; and Group C, blot-dried so that the dentine surface
      remained visibly moist. The three categories of primers were applied to each disc
      in 8-10 coats, resulting in nine sub-groups. Discs in each sub-group were bonded
      together to form disc-pairs using a chemical cure resin, demineralized in
      ethylene diamine tetraacetic acid (EDTA) and prepared for transmission electron
      microscopic examination. RESULTS: With the use of the water-free primer version,
      sub-optimal hybridization was observed whenever dentine was dried prior to
      bonding (Groups IA and IB). In the 5% water version, prolonged desiccation
      resulted in compromised hybridization (Group IIA), while resin globules were
      observed on the surface of the hybrid layer when a moist technique was employed
      (Group IIC). In the 17% water version, surface blisters and globules
      characteristic of the 'overwet phenomenon' were observed in Groups IIIB and IIIC.
      CONCLUSION: Between the two extremes of a morphological spectrum of bonding
      conditions, the different primer versions exhibited different sensitivity ranges.
      There was a shift in the 'window of opportunity' for optimal hybridization and
      tubular seal depending on the water content of the primer system investigated.

PMID- 9540311
TI  - Determination of leachable components from four commercial dental composites by
      gas and liquid chromatography/mass spectrometry.
AB  - OBJECTIVES: The purpose of our study was to determine the quality and quantity of
      leachable residual (co)monomers and additives eluted from various commercial
      dental composite resins after polymerization. METHODS: Polymerized specimens from
      four universal hybrid-type composite resins were eluted for 3 days with methanol
      resp, water. Then all extracts were analysed by gas chromatography/mass
      spectrometry or liquid chromatography/mass spectrometry using a particle beam
      interface. RESULTS: In all polymerized composite resin specimens, (co)monomers
      and various additives as well as contaminants from manufacturing processes were
      identified. Almost every compound detected in the unpolymerized resins could also
      be identified in the methanol extracts, but only a few of them were found in the
      water extracts. From these the co-monomer TEGDMA was extracted in quantities
      higher than those reported to be cytotoxic in primary human oral fibroblast
      cultures. CONCLUSIONS: From our results we conclude that the extractable
      quantities of composite resin components should be minimized, either by reducing
      the mobility of leachable substances within the set material or by applying less
      water-soluble components. Furthermore, all ingredients of a dental composite
      should be declared by the manufacturers, in order to identify those substances in
      a product which may cause adverse side effects in patients and dental personnel.

PMID- 9540313
TI  - Bonding efficacy and interfacial microstructure between resin and dentine primed
      with glyceryl methacrylate.
AB  - OBJECTIVES: To evaluate the effect of two experimental primers based on glyceryl
      methacrylate (GM, 2,3-dihydroxypropyl methacrylate) and 2-hydroxyethyl
      methacrylate (2-HEMA) on the marginal adaptation of light-cured composite placed
      into cylindrical dentine cavities and to study the interfacial microstructure.
      METHODS: The bonding efficacy of two experimental dentine primers combined with a
      dentine cleanser composed of either 0.5 mol l-1 EDTA neutralized to pH 7.4 by
      sodium hydroxide or 10% citric acid containing 3% ferric chloride (10-3
      solution), and a commercial dentine bonding agent containing phosphate ester,
      were examined by measuring the wall-to-wall polymerization contraction gap of a
      commercial light-activated resin composite placed into cylindrical dentine
      cavities. The adhesive interface between the dentine and the dentine adhesive was
      observed using a transmission electron microscope (TEM). RESULTS: The formation
      of a contraction gap was completely prevented by priming with GM, regardless of
      the dentine cleanser used. However, in groups primed with 2-HEMA, gap formation
      was observed in three and four specimens out of 10 in the groups that were
      cleaned with the EDTA and 10-3 solution, respectively. In samples primed with GM,
      a high-density layer was observed by TEM at the superficial dentine in the hybrid
      layer, which may have indicated a high monomer content, whereas no density
      variations were observed in the hybrid layer in samples primed with 2-HEMA.

PMID- 9540314
TI  - Photoelastic analysis of polymerization contraction stresses in resin composite
      restorations.
AB  - OBJECTIVES: The objective of this study was to determine the distribution and the
      magnitude of the internal stresses in a resin composite restoration resulting
      from polymerization shrinkage by using photoelastic analysis. METHODS: Butt-joint
      box-shaped cavities (5.0 x 2.0 mm, 2.0 mm in depth) prepared in bovine teeth and
      in composite moulds were filled with the light-activated transparent composite.
      The restoration was cross-sectioned perpendicularly to the longitudinal side of
      the cavity and observed with polarized microscopes. The principal stresses of the
      restoration, normal and shear stresses at the cavity wall were evaluated by the
      graphical integration method. The integrity of the bond along the cavity wall was
      also examined by staining method. RESULTS: The internal stresses of the
      restorations in bovine teeth were not large enough to observe, apparently because
      the gaps along the dentinal wall acted as a stress relief. On the other hand,
      there were no gaps along the cavity walls at the restorations in the composite
      moulds. As flow of the resin composite was severely limited, the maximum normal
      tensile stress at the cavity wall, which occurred near the internal line angle of
      the cavity, was calculated to reach as high as 23 MPa. The stress level near the
      internal line angle was higher than that near the cavo-surface margin.
      CONCLUSION: The distribution of the internal stresses in a composite restoration
      in a box-shaped cavity is considered to be unfavorable for the deep dentin bond.
      A good understanding of these phenomena may improve the clinical effectiveness of
      resin composite restoration.

PMID- 9540315
TI  - Characterization of the development of elasticity in dental luting cements.
AB  - OBJECTIVES: The development of elasticity of dental luting cements was
      investigated as an indicator of working and setting time. METHOD: A displacement
      rheometer was used to monitor the development of elasticity. Three luting cements
      were examined. RESULTS: The initial onset of elasticity in the glass-ionomer and
      polycarboxylate cements did approximate the manufacturer's quoted working times.
      The onset of elasticity did not appear to define a clinically useful working time
      for the zinc phosphate cement. CONCLUSIONS: The development of elasticity in
      luting cements as a measure of working time was not universally relevant. The
      demonstration of the presence of elasticity in some cements may have consequences
      for cementation and all ceramic crown systems.

PMID- 9540316
TI  - Long-term flexural strength of three direct aesthetic restorative materials.
AB  - OBJECTIVES: This investigation evaluates the long-term flexural strength
      behaviour of three different glass-ionomer cement (GIC) based materials. METHODS:
      The materials under investigation were a conventional GIC (Opusfil), a metal
      reinforced GIC (Opus Silver) and a resin-modified GIC (Fuji II LC). Flexural
      strength specimens of the materials were prepared according to the relevant
      manufacturers' instructions for clinical use. After 10-min maturation at 37
      degrees C, the specimens were placed in water, also at 37 degrees C, until
      required for testing. Specimens were tested under four-point bend at intervals
      between 7 and 130 days after manufacture. RESULTS: Opusfil increased in strength
      up to day 56, but was significantly weaker after this time. Opus Silver was
      strongest on day 7, although there was no further decline in strength after day
      14. Fuji II LC increased in strength up to day 14, but there was deterioration in
      strength after day 100. Opus Silver had the highest early strength of the three
      materials, but after day 7 there was no significant difference in strength
      between the three materials under test. CONCLUSIONS: The three cements tested did
      not exhibit the continued increase in strength with time that has been attributed
      to glass-ionomer cements. Each material behaved differently, but they all
      appeared to be adversely affected by storage in aqueous media. Materials formed
      by the inclusion of metal or the incorporation of resins into the glass-ionomer
      cement formulation should be regarded as separate sub-classes of materials in
      their own rights.

PMID- 9540317
TI  - Effect of composite basing on the resistance to bulk fracture of industrial
      porcelain inlays.
AB  - OBJECTIVES: Bases are used in restorative dentistry for several reasons (i.e.
      isolation, elimination of undercuts, etc). Glass ionomers are the standard
      materials used as bases for porcelain inlays, despite the disadvantages of their
      mechanical properties. An alternative basing material is composite: a generous
      layer of posterior composite is cured and shaped in the cavity before an
      impression is taken. The composite basing technique has several clinical
      advantages. The aim of this study was to investigate the effect of the thickness
      of a composite base on the bulk fracture resistance of industrial porcelain, and
      to describe the procedure. METHODS: Fifteen porcelain (P) and 15 composite (C)
      bars, 1-, 2-, and 3-mm thick were joined to form 15 C/P bars, all 4-mm thick.
      Three groups were created: C 1 mm/P 3 mm (group 1), C 2 mm/P 2 mm (group 2), and
      C 3 mm/P 1 mm (group 3). The pairs were joined using Twinlook cement, subjected
      to a three-point bending test and loaded to fracture. The beam theory was used to
      support and explain the results. RESULTS: The fracture load means were: group 1,
      197.7 +/- 18.7 N; group 2, 234.3 +/- 63.3 N, group 3, 336.3 +/- 31.3 N. Group 3
      was significantly stronger than group 1 (P = 0.01) and group 2 (P = 0.03). Groups
      1 and 2 were not statistically different. CONCLUSION: Composite basing is a
      tissue conserving method which may significantly increase the resistance to bulk
      fracture of adhesive porcelain inlays.

PMID- 9540318
TI  - Capturing the pediatric market.

PMID- 9540319
TI  - Why patients ride the information highway.

PMID- 9540320
TI  - The millennium bug: a patient-centered approach to diagnosis and treatment.
AB  - Economic, regulatory, and competitive pressures compete for institutional
      resources, increasing the likelihood that critical delivery systems will be
      missed. Setting patient-centered priorities should now be the primary focus of
      the solution process. Risk assessment should work from the patient out,
      recognizing that the highest risk lies with components that most directly
      influence the care and health of patients. Any successful plan must include
      enough awareness and commitment to ensure the availability of funding and
      resources in a highly competitive environment. The remediation process involves
      both internal expertise and external entities, such as companies selling
      equipment, software, or hardware [8], with outside consultants if experts on year
      2000 problems are not available internally. Aggressive pursuit of solutions to
      the year 2000 problem is essential to preventing severe difficulties at the turn
      of the century.

PMID- 9540321
TI  - A computerized laboratory alerting system in a psychogeriatric unit.
AB  - We evaluated the contribution of a computerized laboratory alerting system to
      patient care in a 34-bed psychogeriatric unit. With this system the results of
      routine laboratory tests are automatically retrieved and registered on a daily
      computer-based medication report. During the first 33 days in which the alerting
      system was in use, a senior psychiatrist monitored the total number of alerting
      messages sent, the number of new messages per day, the number indicating
      physician unawareness, the number already dealt with, and the number that
      initiated a decision to treat the patient or repeat a laboratory test. The
      alerting system retrieved a mean (+/- SD) of 0.77 +/- 0.11 messages per patient
      per day. Twelve percent were new messages and 88% were rotating messages. Three
      resident psychiatrist-case managers were unaware of half the rotating messages
      (i.e., 6% of all messages). Seven percent of the new messages initiated
      treatment, and 15% resulted in laboratory retesting. We conclude that the
      alerting system results in a simple, efficient report that contributes
      substantially to safe patient care.

PMID- 9540322
TI  - Use of neural networks in medical diagnosis.
AB  - In recent years artificial neural networks have been popular both as a subject
      for research and as application tools in various domains. In this study, use of a
      neural network in the prediction of diagnostic probabilities is proposed. When
      the diagnostic probabilities of insulin-dependent diabetes mellitus were
      predicted both by linear regression and by a neural network in an empirical
      experiment, the predictions of the neural network were more accurate than those
      of linear regression. These results suggest that the use of a neural network
      should be considered whenever prediction of diagnosis is required.

PMID- 9540323
TI  - Using a neural network to diagnose the hypertrophic portions of hypertrophic
      cardiomyopathy.
AB  - We studied the ability of a neural network to identify the hypertrophic cardiac
      regions in hypertrophic cardiomyopathy, with the network using
      electrocardiographic (ECG) information alone. Computer-based electrocardiography
      remains a fundamental diagnostic method for analysis of cardiac contour and
      rhythm. Almost all patients with hypertrophic cardiomyopathy have some abnormal
      findings on electrocardiography, but it is very difficult, even for an
      experienced cardiologist, to identify the hypertrophic regions on the basis of
      electrocardiography alone. Since neural networks are known to be better at
      pattern recognition than humans are, we tried using a neural network trained with
      ECG information to identify the hypertrophic regions in hypertrophic
      cardiomyopathy.

PMID- 9540324
TI  - Calculating confidence intervals for threshold and post-test probabilities.
AB  - We describe a method and a computer program, written in JavaScript, for
      calculating confidence intervals. The method uses Taylor's series to approximate
      the standard errors of a post-test probability and threshold probabilities and,
      from them, to obtain the associated confidence intervals. This method is valid if
      the variables of interest are stochastically independent.

PMID- 9540325
TI  - Online medical surveys: using the Internet as a research tool.
AB  - Technologic advances and popularization of the World Wide Web now allow
      researchers to use the Internet for medical surveys. The Internet provides access
      to a rapidly growing and widespread population of potential research subjects.
      Specific populations can be selected from the larger Internet community, which is
      itself becoming more representative of society as a whole. The hypertext markup
      language can be used to create interactive forms with an intuitive and
      intelligent interface. Response collection by means of common gateway interface
      scripts can afford automated data compilation and exportation to other software
      packages. Furthermore, real-time evaluation of incoming data can ensure that the
      data are complete and accurate before they are accepted. Used properly and for
      appropriate research projects, the Internet can provide a fast, cost-effective,
      and efficient mechanism for administering medical surveys.

PMID- 9540326
TI  - Pathophysiology of cerebral ischemia.
AB  - The purpose of this manuscript is to briefly review the pathophysiology of
      cerebral ischemia. Ischemic thresholds are well-defined in lower animals. The
      concept of the ischemic penumbra may include regions of brain around deeper
      regions of ischemia but has also been defined in terms of brain salvageable by
      reperfusion or by pharmacological therapies. The principal pathophysiological
      processes in cerebral ischemia are energy failure, loss of cell ion homeostasis,
      acidosis, increased intracellular calcium, excitotoxicity, and free radical
      mediated toxicity. The underlying biochemical processes are similar regardless of
      the amount of brain that is made ischemic or the duration of ischemia. The
      relative contributions of each process are believed to vary significantly
      especially in relation to the level of cerebral blood flow. Neurons may die by
      necrosis or apoptosis. In the core of an infarct where blood flow is very low,
      the predominant process is energy failure and rapid necrotic cell death.
      Reperfusion of ischemic tissue produces an influx of inflammatory cells and of
      oxygen that can cause increases in oxygen-derived free radicals. Free radicals
      are also important in prolonged ischemia. There is interest in changes in gene
      expression after ischemia. Induction of heat shock proteins suggests that gene
      expression changes may protect neurons from death. Changes in gene expression
      also may initiate apoptosis or other detrimental processes. Although advances
      have been made, there are still no proven pharmacological therapies to rescue
      ischemic human neurons. Such therapies do appear to be on the horizon.

PMID- 9540327
TI  - Arterial occlusive lesions following wrapping and coating of unruptured
      aneurysms.
AB  - Seven patients (mean age 57 years) developed arterial occlusive lesions following
      both wrapping and coating during surgery for unruptured aneurysms. Five patients
      had no risk factors for arteriosclerosis, and two had hypertension or diabetes
      mellitus. The aneurysms were located in the middle cerebral artery in four cases,
      and the internal carotid artery in three. Both 100%-cellulose cotton (Bemsheet)
      and cyanoacrylate glue (Biobond) were used as reinforcement materials.
      Postoperative angiography revealed complete clipping, and no parent artery
      stenoses, although one patient had a non-symptomatic diffuse narrowing in the
      entire carotid fork 7 days following surgery. Three patients had progressive
      stroke 4-5 weeks following surgery, and two had no symptoms. Both reinforcement
      materials were used as little as necessary in the last two patients, but they had
      either transient ischemic attacks or progressive stroke 2 months following
      surgery. Arterial steno-occlusion was confirmed angiographically in all patients.
      These vascular lesions were probably induced by both direct toxicity of the
      cyanoacrylate glue and fibrosis or granuloma formation caused by the cotton
      fibers. The observed angiographical reversibility suggests that the cyanoacrylate
      glue is more likely to be the cause of the lesions than the cotton fibers.

PMID- 9540328
TI  - Acute traumatic subdural hematoma originating from a convexity meningioma--case
      report.
AB  - A 68-year-old male presented with a traumatic subdural hematoma originating from
      a convexity meningioma the day after a motorcycle accident. Computed tomography
      disclosed a right temporal subdural and/or epidural mass. Emergent craniotomy
      revealed a convexity meningioma with thin subdural hematoma. The underlying brain
      was apparently healthy. The histological diagnosis was angiomatous meningioma
      with hemorrhagic foci. The operative and histological findings indicated that the
      tumoral tissue was the source of the subdural hematoma.

PMID- 9540329
TI  - Multiple remote brain hemorrhages after removal of a giant colloid cyst of the
      third ventricle--case report.
AB  - A 59-year-old male presented with progressive gait and memory disturbance.
      Computed tomography (CT) showed a huge high density mass, of about 45 mm maximum
      diameter, in the third ventricle with marked hydrocephalus. Magnetic resonance
      imaging showed the mass as mixed iso- to hypointensity on T2-weighted imaging and
      high intensity on T1-weighted imaging. Bifrontal craniotomy was carried out. The
      histological diagnosis was colloid cyst. Six hours after the operation, a large
      quantity of cerebrospinal fluid (CSF) was discharged via an epidural drainage,
      accompanied by generalized convulsion. CT showed multiple brain hemorrhages and
      subarachnoid hemorrhage remote from the operative field. The cause of hemorrhages
      is obscure, but postoperative overdrainage of CSF through epidural drainage over
      a short time following excessive intraoperative CSF aspiration may have
      contributed to this rare complication.

PMID- 9540330
TI  - Magnetic resonance angiography visualization of four vessel (bilateral carotid
      and vertebral artery) occlusion--two case reports.
AB  - A 44-year-old female with transient vertigo and a 51-year-old female with
      headache and numbness of the hand presented with four vessel occlusion of the
      cerebral arteries (bilateral internal carotid arteries and bilateral vertebral
      arteries). This is an extremely rare entity, and the clinicoradiological features
      are not well documented. Magnetic resonance (MR) angiography visualized the
      cerebral arterial occlusion. Conventional angiography confirmed the diagnosis and
      demonstrated extensive collateral vessels. MR angiography is a useful method for
      screening patients with minimal or no symptoms for abnormalities in the cerebral
      circulation.

PMID- 9540331
TI  - Superior sagittal sinus thrombosis associated with primary antiphospholipid
      syndrome--case report.
AB  - A 36-year-old female with a history of recurrent pregnancy loss experienced
      sudden onset of disturbance in consciousness, with right hemiparesis and total
      aphasia. Computed tomography revealed a massive hemorrhage in the left frontal
      lobe, and angiography showed occlusion of the anterior two-thirds of the superior
      sagittal sinus. Laboratory investigations detected the presence of lupus
      anticoagulant, elevation of the anticardiolipin beta 2-glycoprotein I complex
      antibody level, and a decreased protein S activity level. There were no
      underlying conditions, such as connective tissue disorders, malignancies,
      infectious diseases, and drug-induced disorders, so the diagnosis was primary
      antiphospholipid syndrome. Primary antiphospholipid syndrome should be considered
      in the evaluation of patients with "idiopathic" or "primary" sinus and cerebral
      venous thrombosis.

PMID- 9540332
TI  - Association of a dolichoectatic middle cerebral artery and an intracranial
      cavernous hemangioma--case report.
AB  - A normotensive, non-smoking 41-year-old female with a history of generalized
      seizures from the age of 4 years presented with a left middle cerebral artery
      (MCA) fusiform aneurysm and an ipsilateral frontal lobe cavernous hemangioma.
      Surgical exploration demonstrated that the fusiform aneurysm-like lesion was a
      dolichoectatic MCA with no arteriosclerotic change. The pathogenesis of
      dolichoectasia is obscure, but the association of a dolichoectatic MCA and an
      intracranial cavernous hemangioma is suggestive of congenital factors.

PMID- 9540333
TI  - Sigmoid sinus dural arteriovenous malformation resulting from jugular foramen
      schwannoma--case report.
AB  - A 69-year-old male presented with a jugular foramen schwannoma occluding the
      sigmoid sinus and associated with sigmoid sinus dural arteriovenous malformation.
      The patient presented with dizziness and pulsatile tinnitus following an extended
      period of hearing loss beginning several years before. Both lesions were resected
      successfully after transarterial embolization of the malformation. The sequence
      of symptom development suggests the dural sinus thrombosis caused the dural
      arteriovenous malformation.

PMID- 9540334
TI  - Subependymoma in the lateral ventricle incidentally detected by routine brain
      examination--case report.
AB  - A 42-year-old male visited our hospital for a routine brain examination, which
      incidentally identified an intraventricular mass lesion (2.7 x 1.6 x 1.2 cm3).
      Magnetic resonance imaging showed the tumor was isointense on the T1-weighted
      image and hyperintense on the T2-weighted and proton images. The intraventricular
      tumor was totally extirpated through the interhemispheric ipsilateral
      transcallosal approach. The histological diagnosis was subependymoma.
      Neuroimaging cannot differentiate this benign neoplasm from other more aggressive
      tumors. Widespread use of the medical checkup system is expected to find a higher
      incidence of otherwise non-identified asymptomatic lesions. Surgical extirpation
      is one of the treatment options to establish the correct diagnosis and to prevent
      symptoms.

PMID- 9540335
TI  - Neuroimaging appearance of pituitary abscess complicated with close inflammatory
      lesions--case report.
AB  - A 13-year-old girl with a pituitary abscess complained of continuous headache and
      bitemporal hemianopsia after a common cold. However, she had no inflammatory
      reactions on admission. Computed tomography showed a low-density sellar mass
      lesion extending to the suprasellar cistern with a peripheral low-density area,
      and ring enhancement of the capsule with a particularly thick region. Magnetic
      resonance imaging showed the mass lesion as a low- and high-intensity area on the
      T1- and T2-weighted images, respectively. The iso-intense rim of the lesion and
      the left frontal mass lesion adjacent to the capsule were enhanced by gadolinium
      diethylenetriaminepenta-acetic acid. Magnetic resonance imaging also indicated
      only mild sphenoidal sinusitis which may be representative of the inflammatory
      process. Careful assessments of neuroimaging findings and preceding trivial
      inflammatory signs are necessary for the correct diagnosis of a pituitary
      abscess.

PMID- 9540336
TI  - Intraligamentous cervical disc herniation: a microneurosurgical observation.

PMID- 9540337
TI  - Chemistry and biochemistry of 8-aminoflavins.

PMID- 9540338
TI  - Densitometric approach to characterizing choroidal neovascular membranes.
AB  - The purpose of this study was to determine the nature of the relationship between
      density of indocyanine green (ICG) and the activity of occult choroidal
      neovascular membranes (CNVM) in patients with age-related macular degeneration
      (AMD) using ICG angiography. Ten eyes of ten patients with AMD and associated
      CNVM formation were retrospectively classified into either active or silent group
      on the basis of clinical outcome. Density of ICG for ICG leakage of CNVM was
      retrospectively determined from baseline ICG angiograms using an image analysis
      system. The means of relative density of the two groups were significantly
      different at five minutes after injection of ICG (p = 0.02). Densitometric
      analysis with ICG angiography may enable the discrimination of active from silent
      CNVM in patients with AMD, and thereby, prove useful in guiding clinical decision
      concerning treatment of these patients.

PMID- 9540339
TI  - A histopathological study on localization of hepatitis C virus RNA in liver of
      chronic hepatitis C.
AB  - By in situ hybridization (ISH) method using digoxygenin (DIG)-labeled RNA probe,
      we proved the localization and replication of hepatitis C virus (HCV) RNA not
      only in the hepatocytes but also in the lymphocytes of the 52 liver tissues of
      chronic hepatitis C. We classified the staining patterns into four groups. The
      pattern of signal distribution significantly correlated with serum alanine
      aminotransferase (ALT) level, quantity of serum HCV RNA just before liver biopsy,
      histological grade of inflammatory activity, and stage of fibrosis by Spearman
      rank correlation. Moreover, we investigated the relation between the signals in
      the hepatocytes or lymphocytes and the effectiveness of interferon (IFN) therapy.
      Therefore, we suggest that ISH is a useful tool to evaluate the activity of
      chronic hepatitis C associated with serological and histopathological changes and
      is an important marker to assess the effectiveness of IFN treatment.

PMID- 9540340
TI  - Functional evaluation of flail hip joint after periacetabular resection of the
      pelvis.
AB  - Five patients subjected to flail hip joint after resection of primary bone tumor
      of the pelvis involving acetabular region were examined with respect to function.
      When a thick portion of the supraacetabular pelvic neck was left in place, the
      operated legs functioned well regardless of whether the head of the femur was
      placed anterior or posterior to the iliac wing. In a patient who had only a thin
      portion of the iliac wing left in place and in those who underwent total excision
      of the ilium or hemiresection of the pelvis, the function of operated legs was
      poorer than with a thick portion of the supraacetabular pelvic neck left in
      place, but still more than 50% of leg function remained. Although flail hip joint
      results in a larger leg-length discrepancy than do other techniques, it enables
      favorable healing of the operative wound. Therefore, this method should be
      considered for women or sedentary patients with primary bone tumor of the pelvis
      involving acetabular region.

PMID- 9540341
TI  - Clinical studies of second revision in total hip replacement.
AB  - Eleven patients (12 hips) underwent the second revision of total hip replacement.
      The mean age at the second revision was 61 years (range: 31 to 79); 2 patients
      were men and 9 women. Loosening of components was the most common reason for the
      revision surgery. Supplemental ring or wire-mesh reinforcement was used for the
      revision of the acetabular that had poor bone stock. On the acetabular side, an
      allograft was used in 4 hips; on the femoral side, a long stem was used in 11
      hips. The mean operative time was 298 minutes (range: 195 to 525), and the mean
      bleeding volume was 2278 ml (range: 810 to 4800) which was about twofold more
      than that of the primary operation. The mean length of follow up after the second
      revision was approximately 5 years. In the clinical results, the mean total Japan
      Orthopaedic Association score was 56 points before the second revision and it was
      70 points during the follow-up period. Pain score was especially improved after
      the second revision. On final roentgenographic examination there was noted a
      clear zone in three acetabular components and five femoral components. As yet, we
      have not experienced any case requiring a third revision.

PMID- 9540342
TI  - Flow cytometric analysis of leukocytes and reticulocytes stained with proflavine.
AB  - Proflavine, an acridine analog for industrial use, was used to stain blood cells.
      A drop of blood treated with ethylenediaminetetraacetic acid-2K was mixed with a
      0.00001% solution of the dye and observed immediately by fluorescence microscopy
      with a green filter. Leukocytes, platelets, and reticulocytes were stained but
      mature red blood cells were not. Chromatin in the nuclei of all leukocytes and
      nucleoli of lymphocytes and monocytes had greenish-yellow fluorescence, and the
      kind of cell could be identified by the tone and intensity of this color.
      Granules in granulocytes were in green. Reticular fine-granular or granulofibrous
      structures in the reticulocytes were brownish. The proflavine could be used
      routinely in clinical laboratories because this single stain makes possible
      simultaneous differentiation of leukocytes and counting of reticulocytes.

PMID- 9540343
TI  - Kinetic analysis of glucose metabolism by FDG-PET versus proliferation index of
      Ki-67 in meningiomas--comparison with gliomas.
AB  - I compared glucose metabolism by 18F-fluorodeoxy-glucose (FDG)-PET with
      proliferative potentials determined by using Ki-67 in meningiomas and gliomas. Ki
      67 labeling index (LI) as proliferation index was used to assess tumor
      aggressiveness. In FDG-PET, I measured tumor versus contralateral gray matter
      ratio (T/N), standardized uptake value (SUV), kinetic rate constants (k1, k2, k3)
      which were analyzed according to the three compartment FDG model, and kinetic
      cerebral metabolic rate of glucose (kCMRGl). Significantly elevated FDG uptake in
      T/N, kCMRGl was found in a high Ki-67 LI (above 2%) group compared to a low Ki-67
      LI group in gliomas, but there was not found significant difference between these
      two groups in meningiomas. Tumor k3 value, an indicator of hexokinase activity,
      of a high Ki-67 LI group was significantly higher than that of a low Ki-67 LI
      group. It was found that k3 correlated with Ki-67 LI. The k3 value is useful for
      estimating the biological aggressiveness of meningiomas.

PMID- 9540344
TI  - Histopathological features of pulmonary asbestosis with particular emphasis on
      the comparison with those of usual interstitial pneumonia.
AB  - We examined 40 autopsy cases of pulmonary asbestosis which were defined by
      occupational history, lung fibrosis and asbestos bodies (ABs) to clarify
      histopathological features. Thirty four patients were males and six were females.
      The mean age was 64.1 +/- 1.6. Gross findings of 39 cases (one case was examined
      only microscopically) showed that pleural adhesion in 31/39, visceral pleural
      thickening in 37/39, and pleural plaques in 26/33 except of 6 cases with severe
      adhesion. Four cases had no or only mild pleural adhesion or pleural thickening,
      and no pleural plaques. Grossly, lung fibrosis of asbestosis can be divided into
      two types of honeycombing (HNCB) predominant fibrosis (16 cases), and atelectatic
      induration predominant fibrosis (23 cases). Histologically, the honeycombing type
      fibrosis showed peripheral acinar fibrosis like in usual interstitial pneumonia
      (UIP), whereas the atelectatic induration type exhibited non-peripheral acinar
      fibrosis with intraluminal organization unlike in UIP. In our study, the lung
      fibrosis was more intensive in the lower lobes, posterior and subpleural zones,
      although in eight cases the upper lobes were more intensively involved than the
      lower lobes. The degree of asbestos body formation on each case was varied. Four
      cases with typical honeycombing and fibrosis grade 3 were counted only small
      numbers of asbestos bodies, and lacked one or two above-described pleural
      changes, and these cases were similar to idiopathic or usual interstitial
      pneumonia (UIP). As for complications of asbestosis, 13 cases (32.5%) had lung
      cancer and 14 cases (35%) presented diffuse alveolar damage (DAD) pathologically.
      It is concluded that asbestosis cases of honeycombing type without pleural
      changes can not be distinguished even from UIP, if asbestos bodies (ABs) were not
      found histologically. Therefore, great care needs to be taken in identifying
      them. We also have examined the quantitatave counts of asbestos bodies and
      asbestos fibers in ten cases. Acute exacerbation of UIP is a well recognized
      entity in Japan, similar condition may occur in pulmonary asbestosis.

PMID- 9540345
TI  - Effect of amrinone on portal hemodynamics and tissue blood flow in the isolated
      perfused rat liver.
AB  - We studied the effect of amrinone on portal perfusion pressure, perfusion flow,
      and tissue blood flow using an isolated perfused rat liver model. In the constant
      perfusion flow model, amrinone effectively decreased perfusion pressure in the
      precontracted state by adenosine triphosphate (ATP) or norepinephrine. Amrinone
      dose-dependently decreased portal perfusion pressure increased by calcium
      chloride. Similarly, amrinone dose-dependently increased portal perfusion flow
      decreased by ATP in the constant perfusion pressure model. Amrinone effectively
      increased tissue blood flow decreased by ATP or norepinephrine measured by laser
      Doppler flowmetry. A specific inhibitor of the biosynthesis of nitric oxide, N
      omega-nitro-L-arginine, did not affect the hemodynamic effect of amrinone,
      suggesting that nitric oxide is not involved in the portal vasodilating effect of
      amrinone. We conclude that amrinone increases portal blood flow by decreasing
      perfusion pressure and contributes to increasing tissue blood flow of the liver
      without the involvement of nitric oxide.

PMID- 9540346
TI  - A preliminary study of HLA class II alleles in Thai patients with non Hodgkin's
      lymphoma.
AB  - The HLA class II alleles were analyzed by the PCR-SSP technique in the DNA
      samples obtained from 27 Thai patients with non Hodgkin's lymphoma (NHL). It was
      found that (1) the incidence of HLA-DRB1*15 and HLA-DRB1*09 was slightly
      decreased (P > 0.05). On the other hand, the incidence of HLA-DQB1 alleles was
      the same as control. However, further study is suggested in order to conclude the
      close relationship between the presence of certain HLA class II alleles and
      susceptibility to NHL in Thai patients.

PMID- 9540347
TI  - Clonal analysis of cancer cells that survived anticancer drug treatment.
AB  - We hypothesized that postchemotherapeutic recurrent cancer cells consist of
      sensitive cells and resistant cells. To examine this hypothesis, the clonality of
      the postchemotherapeutic surviving cancer cells was characterized. The
      postchemotherapeutic surviving cancer cells was established using a human
      cervical carcinoma cell line, ME180, in which cells were treated with either
      SN38, VP16, or THP for more than 8 weeks. The surviving cells were subcloned by
      limiting dilutions yielding the following cloning efficiencies: 18% for SN38, 26%
      for VP16, and 57% for THP. Characterization of the established subclones proved
      that the postchemotherapeutic recurrent cancer cells consisted of both sensitive
      cancer cells and resistant cancer cells. This result supports the hypothesis and
      hence points toward improvement of chemotherapeutic effect through an
      understanding of the dual types of surviving cells.

PMID- 9540349
TI  - Surcharge savings estimated at $24 million for PA physicians.

PMID- 9540348
TI  - CJC continues fight for tort reform.

PMID- 9540350
TI  - New Medicare program offers choices--and new rules.

PMID- 9540351
TI  - Medicare private contracting conundrum.

PMID- 9540352
TI  - Medicare final rule ups primary care fees.

PMID- 9540353
TI  - Our most powerful political tool? You!

PMID- 9540354
TI  - And they said it couldn't be done! DUR program celebrates fifth year.

PMID- 9540356
TI  - CJC moves one step closer to announcing tort proposals.

PMID- 9540355
TI  - Managed care bill set for Senate consideration.

PMID- 9540358
TI  - Dealing proactively with managed care.

PMID- 9540359
TI  - Physician recruitment in rural Pennsylvania.

PMID- 9540361
TI  - Addressing perceptions of the impaired physician.

PMID- 9540362
TI  - Center expands drug education focus.

PMID- 9540363
TI  - [Prostacyclin and iloprost in aerosol form in severe pulmonary hypertension].

PMID- 9540364
TI  - [Effect of salmeterol in obstructive sleep apnea syndrome].
AB  - The effect of inhaled long-acting beta 2-agonists on obstructive sleep apnoea
      syndrome (OSAS) is unknown, though from the pharmacological point of view both
      therapeutic and adverse effects might be discussed. The purpose of this study was
      to obtain data on the efficacy and safety of Salmeterol in patients with OSAS. In
      a randomised, double-blind, placebo-controlled, crossover study effects of
      Salmeterol were investigated in 20 patients with OSAS: 4 female, 16 male; age
      53.0 +/- 7.8 years, body mass index (BMI) 28.0 +/- 3.0 kg.m-2; apnoea hypopnoea
      index (AHI) 35.6 +/- 17.8 h-1. Patients with asthma, chronic obstructive
      pulmonary disease (COPD), and left heart failure were excluded. Placebo or verum
      (50 micrograms Salmeterol) were administered at 7 p.m. by metered dose inhaler
      and spacer device. All patients underwent full polysomnography during baseline,
      placebo, and verum night. Statistical analysis was performed by Student's t-test
      (p < 0.05). Between placebo and verum there were no differences in total sleep
      time, sleep stages, apnoea index (AI), AHI, and nadir SaO2. There was, however, a
      significant deterioration of mean SaO2 (placebo 93.1 +/- 2.0 vs Salmeterol 92.5
      +/- 2.2%) and of relative time spent with SaO2 < or = 90% (placebo 13.1 +/- 14.5
      vs Salmeterol 19.5 +/- 20.8%), as well as a significant increase in heart rate
      (placebo 63.1 +/- 9.2 vs Salmeterol 65.6 +/- 9.3 h-1). Thus, in patients with
      OSAS Salmeterol had no adverse effect on quality of sleep, AI or AHI. The slight
      increase in heart rate and the deterioration of oxygen saturation are clinically
      irrelevant. The latter might be due to ventilation-perfusion-mismatch. This study
      demonstrates that Salmeterol has no influence on obstructive sleep apnoea and
      hypopnoea, but on the other hand provides an acceptable safety profile in OSAS.
      This might be of special importance in patients suffering from both OSAS and
      obstructive airway disease.

PMID- 9540365
TI  - [Effectiveness and tolerance of a combination of fluticasone and salmeterol in
      patients with obstructive airway diseases. DUO Study Group].
AB  - The purpose of this open multicentre study was to evaluate prospectively the
      efficacy and safety of a combination of fluticasone (250 micrograms b.i.d.) and
      salmeterol (50 micrograms b.i.d.), both given by a metered dose inhaler, in 413
      patients (mean age [+/- SEM] 46.9 +/- 0.7 years) suffering from obstructive
      airways disease (FEV1 % predicted 73 +/- 1.1%) for 10 +/- 0.5 years. 8 weeks of
      therapy with both drugs improved FEV1 and peak expiratory flow by 24 +/- 3.1% and
      27 +/- 2.7%, respectively. Daytime and nocturnal symptoms, rescue beta 2 agonist
      use, days off work, and symptoms during working hours decreased. Similarly, the
      quality of sleep improved (p < 0.001, all comparisons to baseline). More than 80%
      of patients and physicians independently classified the study medication as
      superior to their previous therapy. Adverse events possibly, likely or definitely
      related to the study medication were seen in 9% of patients. In conclusion, an
      inhaled corticosteroid (fluticasone) together with an inhaled long-acting beta 2
      agonist (salmeterol) is an effective and well tolerated therapy in patients with
      obstructive airways disease.

PMID- 9540366
TI  - [Alveolar hemorrhagic syndrome in sarcoidosis].
AB  - BACKGROUND: Alveolar hemorrhage is uncommon in sarcoidosis, even in the presence
      of severe alveolitis. PATIENT: A heavy smoker with bihilar adenopathy presented
      with severe alveolar hemorrhage in the absence of radiological signs of pulmonary
      involvement. Sarcoidosis was confirmed histologically by transbronchial and
      mediastinal lymph node biopsies. The bleeding stopped before the installation of
      anti-inflammatory medication and did not reoccur within 9 months of follow up,
      but BAL analysis demonstrated the persistence of alveolar siderophages.
      CONCLUSIONS: Sarcoidosis should be considered as a rare cause of diffuse alveolar
      hemorrhage.

PMID- 9540367
TI  - [Latex allergy: local hypersensitivity reaction cause by an esophageal catheter
      in compliance determination].
AB  - We report on two latex-allergic subjects who developed local hypersensitivity
      reactions after their lung compliance was measured by an oesophagus balloon
      catheter. Protein and allergen analyses of this catheter showed values of 85 and
      9.8 micrograms per gram rubber. It is concluded that latex-allergic subjects
      should not undergo examinations with latex allergen-containing catheters. To our
      knowledge, this is the first report on allergic reactions caused by latex
      balloons of an oesophagus catheter.

PMID- 9540368
TI  - [The German Society of Pneumology: recommendations for diagnosis and therapy of
      sarcoidosis].

PMID- 9540369
TI  - ["Questionnaire on Quality of Life in Asthma"--studies of the dimensionality and
      references for evaluation].
AB  - The FLA, representing the German revision of the LWAQ (Hyland et al., 1991), is
      one of the few available questionnaires for measuring the disease-specific
      quality of life (QOL) in adults suffering from asthma. The present study aimes at
      analysing the structure and reliability of the FLA and also at improving its
      feasibility. Therefore, the inventory has been analysed in terms of its
      dimensional structure, internal reliability, and homogeneity. To facilitate the
      interpretation of the test outcomes and to obtain more differentiated predictors,
      the 40 items of the FLA were--according to theoretical considerations-
      categorised into three dimensions ("Physical Symptoms", "Psychological Distress"
      and "Functional Status"). In this study the FLA was applied with a sample of 136
      hospitalised asthma patients of varying severity (63 male, 73 female, meanage;
      49.5 years) in the North German "Allergie- und Asthmaklinik Wilhelm Gronemeyer,
      Bad Lippspringe, to evaluate the reliability of the total scale and its
      dimensions. The findings of the item analysis with regard to selectivity and item
      difficulty yielding satisfying results are presented in multiple tables.
      Furthermore, recommendations for the transformation of original values into
      summary scores and evaluation procedures were developed to improve the strength
      of evidence in the data. The summary scores, which can be computed for both total
      scale and the three dimensions, facilitate intra- and interindividual comparison
      of the patients' quality of life and point to special deficits in different QOL
      domains requiring specific therapeutic interventions. Finally, the FLA's range of
      application, its limitations, developmental perspectives and proposals for
      improvement are discussed.

PMID- 9540370
TI  - [Sports and exercise in asthma therapy. With sports and exercise therapy for
      improved quality of life].

PMID- 9540371
TI  - [Ambulatory asthma sports group is examined].

PMID- 9540372
TI  - [Value of exercise therapy as a means for therapy and rehabilitation].

PMID- 9540373
TI  - [Functional prerequisites for participation in asthma sports therapy and
      possibilities for follow-up evaluation].

PMID- 9540374
TI  - [Patient education--dream, future and reality--education from a completely
      different point of view].

PMID- 9540375
TI  - [Spinach powder-induced exogenous allergic alveolitis].
AB  - A 51-year old woman developed hypersensitivity pneumonitis to spinach powder,
      which is used as a food dye. The diagnosis was confirmed by demonstration of IgG2
      antibodies in the patient's serum to distinct bands of spinach extract by Western
      blotting. Furthermore an exposure test with the natural allergen was positive.
      Severe disease with fever, chills and dyspnoea developed after inhalation of
      native spinach powder. Arterial pO2 dropped significantly and pulmonary function
      tests showed severe restrictive impairment and reduction of diffusion capacity.
      Leucocyte count and the serum concentrations of the cytokines TNF alpha and IL6
      and of the soluble IL2-receptor rose significantly in peripheral blood, whereas
      the concentration of neopterine did not change. 24 hours after exposure
      bronchoalveolar lavage showed an increase of neutrophils. In lung parenchyma
      mononuclear interstitial infiltrates and an epitheloid cell granuloma were seen.

PMID- 9540376
TI  - [Pain and its treatment].

PMID- 9540377
TI  - [Pain as a biological phenomenon of consciousness].
AB  - Pain has not to be considered a false step of nature. On the contrary, it is an
      extremely effective warning mechanism through which the individual becomes aware
      of a danger to its own physical integrity from inside the body or from the
      environment. Pain therefore belongs to the biological devices for evading bodily
      danger. The conscious experience of pain is the most sophisticated stage of
      evolution of warning systems, whose simplest form is represented by an
      unicellular organism which moves away if it anticipates danger from an
      environmental state. Similar to all qualia, conscious experience of pain cannot
      be fully explained in terms of neurophysiological events. Conscious pain is a
      complex perceptual and affective experience influenced not by the amount of the
      bodily lesion alone, but also by the whole personality of the sufferer. This
      often makes surgical, medical and psychological treatment of pain difficult and
      disappointing.

PMID- 9540379
TI  - [Pain management from the viewpoint of the anesthetist].
AB  - In a pain clinic team the anesthetist has the knowledge and experience concerning
      the peripheral and central neural blockades. The value of the diagnostic,
      prognostic and therapeutic blockades is today under discussion. Patients with a
      chronic regional pain syndrome (CRPS) can find some relief with a series of
      somatic and sympatholytic blockades, which allow an aggressive physiotherapy.
      Epidural steroid injections are helpful in radiculopathic pain. In other types of
      pain (neuropathic, postherpetic, failed back surgery syndrome, abdominal, cervico
      cephalgic, phantom limb pain und tumor pain) the spinal cord stimulation (SCS)
      and the intrathecal morphine pump are approved methods for intactable pain.

PMID- 9540378
TI  - [Anatomic-physiologic principles of pain].
AB  - Pain, particularly chronic pain, arises from the interaction of multiple
      simultaneously operating physiologic processes. The current understanding of the
      anatomy and physiology of pain is limited to a characterization of pathways and
      does not explain why a particular stimulus is felt as pain of a particular kind
      and intensity. In this article, we trace the afferent pain pathways from
      periphery (reception) to center (perception), i.e., from peripheral nerve,
      through the spinal cord and brain stem, to the thalamus and cerebral cortex. A
      number of neurosurgical procedures for the treatment of pain are discussed, and
      their anatomic basis is explained.

PMID- 9540380
TI  - [Interdisciplinary pain consultation or pain conference--multidisciplinary,
      comprehensive pain management].
AB  - From the perspective of an anesthesiologist longstandingly active in pain
      diagnostic and pain treatment the pain interview, the interdisciplinary pain
      consulting and the interdisciplinary pain conference as well as the
      multidisciplinary pain treatment are elucidated. The value of the
      interdisciplinary pain conference is viewed in the context of comprehensive pain
      treatment. In order to make decisions every feasible way of evaluation and
      subsequent treatment must be recognized. New findings and concepts in
      neurobiology are mentioned since they are invaluable in modern pain treatment.

PMID- 9540381
TI  - [Psychosomatic aspects of chronic pain syndromes. An introduction to diagnosis
      and therapy].
AB  - The approach to chronic pain syndromes must be an interdisciplinary one. Thereby
      the psychiatrist plays an important part. He participates in the diagnostic
      process and undertakes special therapeutic tasks. He must identify the focus of
      the chronic pain syndrome, diagnose psychiatric disorders and describe the
      context of the pain symptoms. The treatment of the psychiatric disorders and the
      effort to cope in a good way may positively influence the development of the
      chronic pain syndrome.

PMID- 9540383
TI  - Factors associated with suicide ideation in adults.
AB  - The study considers numerous factors potentially related to suicide ideation in
      adults, including life stress, stress perceptions, social support, personality,
      alcohol use, chronic conditions, distress symptoms and sociodemographic
      background. Using data from a health survey of 825 adult residents in the urban
      Reykjavik area of Iceland, the study finds that financial hardship, legal stress,
      family difficulties, stress perceptions and low material support are
      significantly related to thoughts of committing suicide. Multiple chronic
      conditions, frequent alcohol use and various forms of distress (e.g. depression,
      anxiety, hopelessness, pain) are also related to suicide ideation. Furthermore,
      low self-esteem and external locus of control (low sense of mastery) are both
      associated with suicidal thoughts. No significant relationships were found
      between sociodemographic background and suicide ideation. The meaning of the
      results, and their implications for continued theoretical and clinical work in
      this area, are discussed. Suicide research has primarily focused on completed
      suicides (e.g. Durkheim [1897] 1951; Fisher et al. 1993; Henry and Short 1954;
      Lester 1974; Pritchard 1996) or suicide attempts (e.g. Diekstra 1982; Maris 1981;
      Slap et al. 1989; Smith and Crawford 1986; Stack and Wasserman 1995). Relatively
      few studies have focused on thoughts of own death or suicide, or suicide
      planning. Nevertheless, there is a growing understanding that ideation and
      planning are important steps in a process of suicide, characterised by a stepwise
      hierarchy of actions with an underlying gradient of severity (Beck 1986; Bonner
      and Rich 1987; Diekstra 1993; Smith and Crawford 1986). Ideation precedes
      planning, which may result in an attempt leading to death. If nonfatal, the
      attempt may increase the likelihood of subsequent ideation, planning and attempt
      (see paths a-e in Fig. 1). It should therefore be of theoretical as well as
      clinical value to consider the risk factors associated with suicide ideation and
      planning.

PMID- 9540382
TI  - [Acute and chronic back and thoracic pain. Non-small-cell bronchial carcinoma].

PMID- 9540384
TI  - Attitudes towards suicide among medical students: comparison between Madras
      (India) and Vienna (Austria).
AB  - Attitudes towards suicide among medical students in Madras (India) and Vienna
      (Austria) were compared using the SUIATT questionnaire by Diekstra and Kerkhof
      (1989). Results show a very restrictive attitude in Madras, rejecting the right
      to commit suicide, nearly always judging suicide as a cowardly act, and rejecting
      the idea of assisted suicide. On the other hand, in Vienna a more permissive
      attitude was found. It is interpreted that the Indian pattern comes close to a
      "medical" or "disease model", with stronger emphasis on mental illness,
      impulsiveness and emotional aspects, whereas the Viennese pattern reflects a
      "theoretical", "rational model", concentrating on cognitive factors and
      minimizing the influence of mental illness, emotional difficulties and
      restrictions related to suicidal behaviour. This pattern may be influenced by the
      public discussion on assisted suicide and the right to die in Europe in the last
      decade. Possible relations to the risk for actual suicidal behaviour are
      discussed using respective answers concerning previous suicidal ideation and
      suicide attempts. The answers concerning suicidal ideation seem to be strongly
      influenced by the different attitude patterns: only 16.8% reported previous
      suicidal ideation in Madras, compared to 51.5% in Vienna, whereas the percentage
      of reported suicide attempts is equal in both centres (5.9%:4.9%).

PMID- 9540385
TI  - Gender differences in symptoms of adolescents reporting sexual assault.
AB  - Sexual assault on children and adolescents has become a common topic of study,
      but there has been little research into the specific characteristics of the
      population of male victims. A national survey representative of school-age
      adolescents in France enabled us to study 465 adolescents reporting sexual
      assault (121 boys, 344 girls; mean age 15.4, SD 2.5 years). Girls were shown to
      be more frequently affected by certain medicopsychological symptoms: nightmares,
      multiple somatic complaints and some items concerning mood disorders. On the
      other hand, behavioural symptoms were much more frequently expressed in boys, in
      particular: repeated suicide attempts, running away, fits of violence and
      substance use. Boys presenting these symptoms should be questioned as a matter of
      routine concerning a history of sexual assault.

PMID- 9540386
TI  - Monthly variation in the care-based incidence of psychopathology.
AB  - Monthly first-contact data from the Groningen Psychiatric Case Register were used
      to study seasonal variation in the care-based incidence of psychiatric morbidity.
      Both overall and diagnosis-specific rates for a 15-year period (1976-1990) were
      examined. Regression analysis of overall rates revealed significant monthly
      deviations from the linear trend. Inspection of diagnosis-specific rates showed
      that the monthly number of first contacts varied most in patients with relatively
      mild psychiatric problems such as neuroses. Seasonal variation is believed to be
      a consequence of both fluctuations in true psychiatric morbidity and 'holiday
      effects' on supply of services and/or the inclination to ask for help. The
      relative influence of holiday effects is assumed to be inversely related to
      psychiatric severity.

PMID- 9540387
TI  - Mental health in the north west region of England: associations with deprivation.
AB  - Minor psychiatric morbidity is known to be associated with social disadvantage,
      but few studies have explored this association at the population level. This
      study reports data from a postal survey across 19 health districts in one region,
      with a total sample of 38,000 respondents. The percentage scoring above the
      General Health Questionnaire (GHQ) threshold for each health district was
      correlated with measures of deprivation derived from the 1991 census and
      standardised mortality ratios. Highly significant correlations were seen between
      the percentage above the GHQ threshold and the Underprivileged Area (UPA) score
      (r = 0.84), under 65 Standardised Mortality Ratio (SMR; r = 0.80), lack of
      amenities (r = 0.56), overcrowding (r = 0.54), lone-parent families (r = 0.84),
      unemployment (r = 0.87), unskilled workers (r = 0.77), ethnic minority
      composition (r = 0.58) and social mobility (r = 0.85). However, the three most
      deprived districts had the lowest response rates and when these were excluded
      from the analysis, only the correlations with under 65 SMR (r = 0.57, P < 0.05),
      UPA score (r = 0.52, P < 0.05) and unskilled workers (r = 0.60, P < 0.05)
      remained significant. There may be a threshold effect for the impact of social
      disadvantage on mental health, with much higher rates of psychological morbidity
      among markedly disadvantaged populations.

PMID- 9540388
TI  - Development and evaluation of an inner city mental health team.
AB  - The objective of this study was to examine the development and activity of a
      Community Mental Health Team, originally targeted to meet the needs of African
      Caribbean, Asian and homeless populations in an inner city area. The study was
      based on all (n = 1046) client referrals to the Bristol Inner City Community
      Mental Health Team between 1987 and 1994. Additional qualitative interviews were
      held with general practitioners (GPs) from each of the nine practices in the
      area. The setting was the inner city area of Bristol, an area with a population
      of around 35,000 27% of whom are from ethnic minority communities. This is an
      area shown in previous research to have a high level of mental health problems.
      Trends in referral rates, demographic characteristics and seriousness of
      psychiatric illness amongst those referred to the Inner City Mental Health Team
      were the main outcome measures used. In the years studied there were significant
      increases in the number and proportion of overall referrals from GPs and
      psychiatrists and decreases in referrals from other agencies. In particular,
      there were reductions in the referral both of clients from the originally
      identified target groups and of patients with serious mental illness. GPs tended
      to refer a greater proportion of patients with less serious mental illness. The
      results of the study showed that a team originally developed to meet the needs of
      the homeless and those from ethnic minorities has, with the removal of special
      project funding, shifted its focus away from the client groups for whom it was
      originally developed to those with less serious mental health problems. These
      changes are partially attributable both to changes in the remit of the team,
      making it more acceptable to GPs, and to a growing acceptance of community-based
      mental health services among GPs and their patients. Changes in the geographic
      catchment area served by the team has also played a role in the observed trends.
      Commissioners of mental health services need to bear in mind the needs of high
      risk groups when making contracts. It may be that in order to meet effectively
      the needs of inner city populations with a high prevalence of mental health
      problems, there is a need for specialist teams with a specific remit.

PMID- 9540389
TI  - A pilot study of needs assessment in acute psychiatric inpatients.
AB  - The needs of acute psychiatric patients have been less studied than those of long
      term patients. A pilot study of needs assessment using the MRC Needs for Care
      Assessment Schedule is reported in 35 consecutive acute inpatients who had been
      in hospital for 1 month or more. Unmet clinical needs included treatment of drug
      side effects and dangerous and socially embarrassing behaviour. Unmet social
      needs were widespread and included household shopping, cooking meals, occupation
      and money management. Although the MRC Needs for Care Assessment was found
      unsuitable for assessing needs in very acutely ill patients whose mental status
      was rapidly changing, we did find it a useful instrument in more stable acute
      patients, both on an individual basis and for identifying service underprovision.

PMID- 9540390
TI  - Reliability of interview information in a family study in the elderly.
AB  - The aim of the present study was to evaluate the combined test-retest and
      interrater reliability of different psychiatric lifetime diagnoses yielded in the
      course of a family study in elderly patients and controls. The following
      interviews and questionnaires were used in combination: the Composite
      International Diagnostic Interview (CIDI), the Structured Interview for the
      Diagnosis of Dementia of the Alzheimer Type, Multi-infarct Dementia and Dementias
      of Other Aetiology (SI-DAM), the General Health Questionnaire (GHQ-12) and
      questionnaires for neurasthenia and recurrent brief depression (RBD). Depressive
      and dementia disorders can be diagnosed with good reliability in a family study
      setting with the use of these instruments. The diagnoses of phobic disorders,
      neurasthenia, RBD, subthreshold RBD and psychiatric caseness as indicated by GHQ
      12 scores were less reliable in this setting and are therefore less suitable for
      use in family studies.

PMID- 9540391
TI  - Surgery and cystic fibrosis.

PMID- 9540392
TI  - Penman Lecture. Inherited thyroid cancer--a review. Delivered at the University
      of Cape Town, 8 February 1995.

PMID- 9540393
TI  - Surgery in cystic fibrosis--a 20-year review.
AB  - The surgical histories of 111 patients with cystic fibrosis (CF) seen between
      1972 and 1991 were examined. Fifty-seven of these children underwent 154
      operations; in 34 the surgery was directly related to CF and accounted for 84
      operations. Meconium ileus and its complications were responsible for 26 of the
      32 major abdominal CF-related procedures and there were 3 major CF-related
      thoracic operations. Only 1 child died within a month of operation. Complications
      occurred in 11.9% of general anaesthetics and post-operative complications in
      9.2% of operations. Patients with CF are likely to need operative intervention
      and, when indicated, surgery should have a low morbidity and mortality.

PMID- 9540395
TI  - Snakebite--rest and elevation in the management of a selected group of patients
      in an urban setting.
AB  - The outcome of snakebite in a selected group of 74 patients is reported. Eight
      patients (10.8%), of whom 2 died, had severe bites. Sixty-six patients (89.2%)
      had minimal signs and symptoms and recovered fully without residual disability
      after bed rest and elevation of the affected limb.

PMID- 9540394
TI  - Importance of the profunda femoral artery in distal limb revascularisation.
AB  - The profunda femoral artery (PFA) was recognised in the early 1960s as an
      essential artery to maintain perfusion in the lower limb. The aim of this
      retrospective study was to analyse the results obtained with aortobifemoral
      bypass surgery (ABF) where the distal perfusion was solely dependent on the PFA.
      An evaluation was made of 240 ABFs done between January 1988 and May 1995. This
      represented a combination of operations done by either the vascular unit at the
      HF Verwoerd teaching hospital or by Dr Van Marle privately. In 56 cases only the
      PFA was available for distal anastomoses in one or both limbs, giving a total of
      80 PFA anastomoses. Evaluation was based on pre- and postoperative ankle brachial
      pulse indexes (ABPI). There were 3 deaths and 1 amputation in the early
      postoperative period. Over an average follow-up period of 32 months (1 month-63
      months) 76 limbs were assessed. At initial presentation 30% of the patients had
      rest pain and 2 already had gangrenous changes. Mean pre-operative ABPI was 0.5.
      A further femoral-popliteal bypass was required within 1 year for 6 of the
      patients. The average postoperative ABPI was 0.86, giving a 73.2% average
      improvement. We therefore concluded that good results can be achieved when the
      PFA is used for distal anastomosis in ABF bypass surgery.

PMID- 9540396
TI  - Comparison of the effects of the interposition of 'narrow' cycloperistaltic v.
      antiperistaltic segments on fluid perfusion through isolated loops of jejunum.
AB  - Experimental studies in dogs showed a delaying action of the cycloperistaltic (C
      P) segment when interposed in isolated loops of jejunum ('narrow' C-P segments)
      and between stomach and duodenum after Billroth I gastrectomies ('wide' C-P
      segments). This study was designed to establish whether there were any
      differences in the delaying action on the passage of perfused fluids between
      isolated loops of jejunum with C-P and antiperistaltic (A-P) segments interposed.
      The latter is the surgical technique that is currently considered the gold
      standard for such actions. Two isolated segments of jejunum with the ends
      exteriorised as jejunostomies (Thiry-Vella (T-V) loops) were created in each of 4
      dogs. Towards the end of one, a C-P segment with a diameter 70% that of the
      jejunum ('narrow' C-P segment) was interposed. Towards the end of the other, a
      reversed A-P segment was interposed. Fluid containing 14C-labelled polyethylene
      glycol was infused at a rate of 4 ml/min through all the 8 loops (4 dogs) for 1
      hour (6 experiments per dog). Descriptive statistics (means and standard errors)
      show that no obvious differences in volume of output, absorption and pooling
      existed between T-V loops with 'narrow' C-P and A-P segments. The delaying effect
      in the passage of fluids of the C-P segment, shown in previous experiments, does
      not appear to be superior to that of the A-P segment. This statement is made with
      some reservation as the number of animals involved was relatively small and
      analytical statistics could not be used.

PMID- 9540397
TI  - Intussusception in adults.
AB  - Adult intussusception is a rare condition, chronic and recurring in nature, and
      presenting as intermittent intestinal obstruction. Surgeons generally have
      limited experience with it. We present 13 cases that have been treated in our
      department over a period of 19 years. In most of the cases there is an
      identifiable cause and it is often a malignancy. Awareness, plain abdominal
      films, barium enema and CT are valuable tools for diagnosis. Resection without
      reduction is the treatment of choice in most cases. In instances where resection
      would necessitate a permanent stoma, attempts at manual reduction are justified.
      Timely treatment, properly carried out, should result in a good prognosis.

PMID- 9540398
TI  - Audit of acute appendicitis in a black South African population.
AB  - This is a prospective study of 212 black South African patients operated on with
      a pre-operative diagnosis of acute appendicitis. There were 143 male and 69
      female patients. Forty-four patients had normal appendices and 122 non-perforated
      and 46 perforated acute appendices. The appendix was normal in 12 male and 32
      female patients. Most presenting signs had a high positive predictive value but
      few had a high negative predictive value. There was no significant difference in
      the systemic response between perforated and non-perforated groups. Delay in
      presentation accounted for the majority of perforated appendices, while there was
      no causal relationship between in-hospital observation and perforation. The
      complication rate was higher and hospital stay longer in the perforated group. We
      concluded that the presentation and clinical course of acute appendicitis in the
      population of black South Africans catered to by our hospital is not very
      different from that in the white population elsewhere in the world.

PMID- 9540400
TI  - Role of radiotherapy in stage III invasive thymomas.
AB  - Twenty-five patients with malignant invasive stage III thymomas who underwent
      biopsy for tissue diagnosis were treated with primary radiotherapy (mean dose
      46.36 Gy, range 32.4-58 Gy). These patients were followed up for a period of 10
      years and survival/failure analysis was performed. Five prognostic variables were
      compared using the log rank test. There was no difference in survival between
      ages less than 50 and more than 50 years, presence or absence of myasthenia
      gravis, sex, histology and race. The mean follow-up was 39 months (range 1-86
      months). The 5-year disease-free survival was 81% overall survival 72% and local
      failure rate 13%. Most local failures occurred in the first 3 months. Six
      patients died after a course of radiotherapy (2 intrathoracic relapse, 1
      disseminated disease, 1 local failure and distant metastasis, 2 causes not
      related to disease). Hilar fibrosis was seen in 4 patients who are asymptomatic.
      No other complications were recorded. Radical external beam radiotherapy alone
      can give good results in malignant stage III invasive thymomas.

PMID- 9540399
TI  - Primary chemotherapy for stage 2 testis cancer.
AB  - To evaluate the efficacy and toxicity of primary chemotherapy in patients with
      stage 2 (retroperitoneal lymph node metastases) testis cancer, 20 consecutive
      patients referred to Groote Schuur Hospital between September 1992 and March 1994
      were reviewed. There were 10 patients with non-bulky non-seminomatous germ cell
      tumour (NSGCT), 5 with bulky NSGCT and 5 with bulky seminoma. The treatment
      regimen consisted initially of 4 cycles of cisplatin, etoposide and bleomycin.
      Patients with NSGCT and a residual mass after chemotherapy subsequently underwent
      retroperitoneal lymph node dissection (RPLND) and those with seminoma underwent a
      low dose of irradiation to the mass. In 7 (70%) of the 10 patients with non-bulky
      NSGCT, there was a complete response to chemotherapy and 3 patients underwent
      limited RPLND. One patient relapsed at follow-up but remains clear of disease
      after salvage therapy. The survival rate is 100% at a median follow-up of 60
      months (range 12-143 months). In 5 patients with bulky NSGCT there was no
      complete response to chemotherapy. Three have undergone limited RPLND. The
      survival rate is 52% at a median follow-up of 130 months (range 108-152 months).
      In 5 patients with bulky seminomas, the survival rate is 100% at a median follow
      up of 55 months (range 29-92 months). Toxicity has been modest except for 1
      patient who died postoperatively in the early part of the study. Four patients
      have fathered children after treatment. We conclude that primary chemotherapy is
      the treatment of choice for patients with stage 2 testis cancer.

PMID- 9540403
TI  - Antivenom in cytotoxic snakebites.

PMID- 9540401
TI  - The use of the flow-volume loop in assessing the results of laryngotracheal
      reconstruction.
AB  - The difficult problem of assessing pre- and postoperative airway function in
      patients with laryngotracheal upper airway obstruction is discussed. A series of
      26 patients with various forms of this problem is presented. The method of
      performing the flow-volume loop (FVL) is described and the theory behind the
      investigation is reviewed. Five of the series of 26 patients are described in
      detail as examples, and the advantages and disadvantages of this investigation
      are discussed fully. The FVL appears to be the only really objective test to
      assist the laryngotracheal reconstructive surgeon. It is easily performed in most
      cases and should form part of the diagnostic and postoperative workup.

PMID- 9540404
TI  - A gene that resuscitates a theory--somitogenesis and a molecular oscillator.

PMID- 9540405
TI  - Ataxia, arrhythmia and ion-channel gene defects.
AB  - Ion channels are essential to a wide range of physiological functions including
      neuronal signaling, muscle contraction, cardiac pacemaking, hormone secretion and
      cell proliferation. The important role that highly regulated ion influx plays in
      these processes has been underscored by a recent flurry of discoveries linking
      ion-channel gene mutations to inherited disorders. Ion channels of many different
      types have been demonstrated as being causative factors in genetic disease. This
      review discusses the growing number of disorders associated with genes of the
      voltage-gated ion channel superfamily, with special focus on those characterized
      by neurological, neuromuscular, or cardiac dysfunction in humans and mice.

PMID- 9540407
TI  - Genetic blindness: current concepts in the pathogenesis of human outer retinal
      dystrophies.
AB  - Outer retinal dystrophies are the major causes of incurable blindness in the
      Western world. Understanding the etiology of retinal dystrophies has improved
      remarkably over the past decade. A number of genes, such as RHO, PDE-beta, RDS,
      TIMP3, MYO7A, RETGC1, RPGR, CRX and ABCR, are now known to be particularly
      important. Characterization of the genetic basis for disease is leading to new
      concepts of pathogenesis at the molecular and cellular levels. Such detailed
      understanding of disease processes is also stimulating a renewed interest in
      therapeutic strategies.

PMID- 9540406
TI  - The fundamental importance of human galactose metabolism: lessons from genetics
      and biochemistry.
AB  - Cloning and characterization of all three human galactose-metabolic genes (GALK,
      GALT and GALE) has led to the identification of a number of mutations which are
      generally of the missense type in patients with galactosemia, an inborn error of
      metabolism. The predominance of missense mutations is interesting, considering
      the general importance of galactose metabolism for cellular energy production and
      proper modification of glycoproteins and glycolipids. Abnormalities in both of
      these macromolecules have been described in transferase-deficiency galactosemia,
      the most common and best-studied form of galactosemia. Thus, the parallel
      biochemical and molecular genetic analyses of human galactose metabolism are
      shedding light on this under-appreciated metabolic pathway that is critical for
      cellular energy production, modification of cellular macromolecules and normal
      human development.

PMID- 9540408
TI  - Retroelements in the human MHC class II region.
AB  - Molecular genetic studies of the human major histocompatibility complex (MHC)
      have led to the identification of more than 200 genes. Besides the large number
      of genes in the MHC, densely clustered areas of retroelements have been
      identified. These include short and long interspersed elements (SINEs and LINEs),
      and human endogenous retroviruses (HERVs). The presence of retroelements in the
      MHC provides a clear example of how these elements affect the genome plasticity
      of the host. Comparative analyses of these retroelements have proven highly
      useful in evolutionary studies of the MHC. Recently, HERV-encoded superantigens
      have been implicated as candidate autoimmune genes in type I diabetes and
      multiple sclerosis. In addition, genetic analyses have revealed that autoimmune
      diseases show strong associations with MHC class II genes. The intriguing
      correlations between retroviral encoded antigens, MHC class II genes and the
      development of autoimmune disease merit intense future investigations of
      retroelements, in particular those endogenous retroviruses located in the MHC
      class II region proper.

PMID- 9540409
TI  - Cholesterol metabolism and embryogenesis.
AB  - Although cholesterol has long been known to be an essential component of cell
      membranes in vertebrate organisms, recent studies have suggested that cholesterol
      plays a crucial role in specific processes during embryonic development,
      including the covalent modification of Hedgehog proteins. Here we review the
      overlapping developmental phenotypes associated with pharmacologically or
      genetically induced defects in cholesterol biosynthesis, embryonic cholesterol
      transport and Hedgehog proteins. Shared aspects of these phenotypes suggest that
      common mechanisms underlie impaired central nervous system development associated
      with cholesterol deficiency.

PMID- 9540410
TI  - ICCBnet: a bioinformatics initiative for developing regions.

PMID- 9540411
TI  - [Rational treatment with antidepressive agents].

PMID- 9540412
TI  - [Neuroosteology].

PMID- 9540413
TI  - [The emotions of physicians. Significance of physicians' emotional reactions to
      the patients].
AB  - During the last thirty years there has been a growing interest in research into
      physician-patient interaction. This article highlights the research which
      concerns the physician's countertransference feelings. The concept of
      countertransference is described and a classification with relevance for
      physicians in general is explained. The existing research into the incidence and
      consequences of countertransference is examined. Examples are given of categories
      of patients, who often evoke specific countertransference feelings in the
      physician. The consequences of the countertransference feelings for the physician
      himself are discussed and examples are given of particular situations where
      countertransference feelings could be of importance. Finally, the existing
      possibilities to learn about handling countertransference feelings are surveyed
      and the authors emphasize the need for more research in this particular field.

PMID- 9540414
TI  - [Multiple system atrophy--a neurodegenerative disease entity].
AB  - Multiple system atrophy (MSA) is a nosological entity. Main clinical
      manifestations are parkinsonism, pyramidal signs, cerebellar signs and autonomic
      dysfunction. Postmortem studies of patients who while alive were diagnosed as
      having idiopathic Parkinson's disease show approximately 8% as having MSA at
      autopsy. Specific pathological findings are glial cytoplasmatic inclusions. It
      seems likely that patients with MSA are misdiagnosed or underrecognized. This
      review is an attempt to elucidate upon clinical and paraclinical approaches to
      MSA and to depict relevant research in this field. The aetiology is unknown.

PMID- 9540415
TI  - [Specific serotonin uptake inhibitors in patients referred to a psychiatrist].
AB  - During a twelve month period (1995), 261 patients were referred to a psychiatrist
      (the author) by their general practitioners. Forty-eight patients (18%) were
      being treated with antidepressive medicine when first seen. Only seven patients
      were being treated with the traditional tricyclic antidepressive medicine, while
      39 received specific serotonin reuptake inhibitors (SSRI) and two patients
      received other kinds of antidepressants. The SSRIs seem to be prescribed to a
      wide range of patients providing an unclear clinical picture, and it is assumed
      that the patients' desire to try the famous and popular pills is crucial when the
      therapeutic decision is made. The weakening of the ontological stase of
      endogenous depression should also not be underestimated.

PMID- 9540416
TI  - [Patient satisfaction with screening for diabetic retinopathy in a hospital
      setting].
AB  - The purpose of the study was to assess how patients appreciate the quality of
      screening examinations for diabetic retinopathy at the Department of
      Ophthalmology, Arhus University Hospital. A questionnaire was given to 500
      consecutive patients who were examined between February and May 1996. Four
      hundred and twenty-nine patients (85.8%) answered and returned the questionnaire.
      Generally, there was satisfaction about the employed examination concept and the
      information and service provided during the examination. Patients in the age
      group between 26 and 35 years demanded more in order to achieve the same level of
      satisfaction as did patients from other age groups. One-third of the patients did
      not know that eye examination with fundus photography can detect diabetic
      retinopathy, but not all other eye diseases. Furthermore, the transport to the
      clinic was a greater problem than expected for patients living more than a few
      kilometers from the hospital. It can be concluded that in the planning of
      screening examinations for diabetic retinopathy, procedures should be designed so
      that the special expectations and needs of patients in the age group of 25-36
      years are fulfilled. Patients should be informed that screening with fundus
      photography only detects retinal changes secondary to diabetes mellitus.

PMID- 9540417
TI  - [Organization of screening for diabetic retinopathy at a department of
      ophthalmology, Aarhus Municipal Hospital].
AB  - This article describes the organisation of screening for diabetic retinopathy at
      The Department of Ophthalmology, Arhus University Hospital, giving a
      descriptional analysis using Leavitt's organisational model. The employed
      organisational model is suitable for offering screening examinations for diabetic
      retinopathy in municipal diabetes teams. The experience gained to date at Arhus
      University Hospital shows that the severity of retinopathy of examined patients
      is similar to that found earlier in Danish diabetes clinics, and the frequency of
      newly diagnosed severe diabetic retinopathy is similar to that of findings from
      other centres.

PMID- 9540418
TI  - [Benzodiazepine consumption in Hvalso. Can it be further reduced in a region in
      which earlier intervention reduced consumption by 38 per cent?].
AB  - Hvalso is a country town with six general practitioners in five practices. In
      1988, as a result of a campaign influencing both doctors and patients, a 38%
      reduction in the consumption of benzodiazepines, measured as the number of
      prescribed doses, was achieved. This reduction still persists. We have now
      attempted to reduce consumption even further by directly influencing the
      individual users. We gave them written information, insisted on personal
      attendance for each prescription renewal, and, for use at these consultations,
      introduced a new benzodiazepine journal for 60% of the users. Registration of the
      prescribed amounts of benzodiazepines was performed over two three-month periods,
      before and after the intervention. The final registration was made six months
      after the intervention period. The number of prescriptions, number of
      prescriptions per 1000 patients and the number of users remained unchanged. A 20%
      reduction in the amount of prescribed sedatives (hypnotics) and a 7% reduction in
      prescribed minor tranquillizers was achieved because of fewer doses per
      prescription. We conclude, that we did not manage to change the patients'
      behaviour, expressed as the number of prescriptions per 1000 patients, but the
      doctors were influenced to write out fewer doses per prescription. Important
      reductions in consumption may be achieved in primary interventions.

PMID- 9540419
TI  - [Microsurgical laser treatment of Zenker's diverticulum. Economic aspects].
AB  - Zenker's diverticulum (hypopharyngeal/proximal oesophageal diverticulum/pouch) is
      a relatively uncommon cause of dysphagia usually in elderly patients. We describe
      the results of the first 10 patients operated for ZD with micro-endoscopic
      laserdiverticulotomy (LD), where the "spur" between the diverticulum and
      oesophagus is coagulated by means of a CO2 laser in our department. The results
      are compared with the results of the last nine patients operated with
      conventional diverticulectomy (DE) via incision on the neck. Two patients in the
      DE group had complications (wound infection and pneumonia), whereas no
      complications were seen in the LD group. An initially good result was seen in all
      the patients in both groups. Symptoms recurred in 11% in the DE group (one
      patient), whereas this was seen in 20% of the patients in the LD group (two
      patients). Re-operation of these two patients in the LD group relieved the
      patients of symptoms, but one patient was re-operated twice before this was
      achieved. Surgery time was reduced by 64%. Hospitalization time was shortened
      from a median of 16 (9-28) days with DE to 4 (0-9) days in the LD group. These
      factors represent a substantial economic saving by using LD as compared to DE. To
      be able to evaluate the result of LD roentgenographically, it has proven
      necessary to produce a pure lateral view of the diverticulum both pre- and post
      operatively. The size and shape of the diverticulum is mostly seen as unchanged
      following surgery. With a pure lateral projection, it is however possible to see
      how the spur between the oesophagus and the diverticulum is diminished with
      resulting enhanced passage of contrast and practically no retention.

PMID- 9540420
TI  - [Prevention and diagnosis of encapsulated endometrium after endometrial
      ablation].
AB  - Endometrial ablation for dysfunctional uterine bleeding has become more common in
      Denmark in recent years. New symptoms and diseases may arise due to morphological
      changes in the uterus after the operation. Despite thoroughness during surgery,
      residual endometrial tissue can be trapped in pockets during the healing process.
      In this paper two cases of encapsulated endometrial tissue are presented in women
      who had undergone endometrial resection. Prophylactic aims, diagnoses and
      treatments are suggested to minimise the risk of residual endometrial tissue in
      terms of concealing the symptoms of a developing adenocarcinoma.

PMID- 9540421
TI  - [Social differences in morbidity and mortality in Western Europe].

PMID- 9540422
TI  - [Picture of the month. [AIDS with CMV chorioretinitis)].

PMID- 9540423
TI  - [Risk of neonatal herpes infections].

PMID- 9540424
TI  - [On locomotives].

PMID- 9540425
TI  - Skin thermoregulation during local cooling in healthy volunteers and patients
      with systemic sclerosis--synchronous assessment of capillary red blood cell
      velocity, laser Doppler flux and skin temperature.
AB  - BACKGROUND: Patients with Raynaud's phenomenon due to systemic sclerosis exhibit
      a functional microangiopathy with endothelial cell damage. The aim of this study
      was to assess differences in the so-called nutritive and thermoregulative skin
      blood flow and to obtain further information by Fourier transformation and by
      nonlinear analysis of laser Doppler flux (LDF) time series. PATIENTS AND METHODS:
      A local cold stress test was performed in 10 patients and 10 age- and sex-matched
      healthy controls. Significant differences were detected between nutritive blood
      flow in the nailfold capillaries, assessed by capillary red blood cell velocity
      (CBV), and thermoregulatory blood flow, which was synchronously assessed by LDF.
      RESULTS: CBV was reduced during cooling, the drop being significantly larger in
      the patients than in the controls. In contrast, there was no significant
      difference in the decrease of LDF during cooling. The difference between the fall
      in CBV values and that in LDF was significantly more pronounced in patients.
      Further analysis of the LDF frequency spectrum by fast Fourier transformation
      revealed a significantly greater decrease in amplitude at the heart frequency
      level in healthy volunteers. A further analysis of the LDF signal revealed
      significant differences at rest and after cooling in fractal dimensions,
      suggesting an increased complexity of LDF signals in patients. SUMMARY: The
      patient's increased sensitivity towards local cold cn be observed best at the
      capillary level. But the changes of LDF in the frequency spectrum during cooling
      as calculated by fast Fourier transformation revealed significant differences. In
      addition differences in fractal dimensions of LDF time series suggest that an
      analysis of nonlinear dynamics may be a promising approach.

PMID- 9540426
TI  - Failure of reducing lower extremity amputations in diabetic patients: results of
      two subsequent population based surveys 1990 and 1995 in Germany.
AB  - BACKGROUND: A 50% reduction of lower extremity amputations during the subsequent
      5 year period has been targeted by the St. Vincent-Declaration issued in 1989/90
      for a better care of diabetic patients across Europe. PATIENTS AND METHODS: In
      two adjacent counties far off major city areas 10 hospitals without specialised
      diabetes centers in the area provide care to about 300,000 inhabitants. Based on
      the official operation books and verified by the individual patient file all
      patients amputated in the 10 hospitals during the years 1990 and 1995 were
      evaluated retrospectively. RESULTS: A total of 119 patients (66 males, 53
      females, age median 72 years) were amputated in the 10 hospitals 1990, and 162
      (89 males, 73 females, age median 74 years) in 1995. The proportion of diabetic
      amputees amounted to 70.6 and 62.3%, respectively. A trend towards more toe
      amputations in diabetic versus nondiabetic patients was seen in both surveys
      which reached significance in 1995 (59 vs. 41%; p < 0.05). Based on the total
      population and the estimated number of diabetic patients (5% of the population)
      1.4 and 2/10,000 nondiabetics were amputated in 1990 and 1995, respectively, in
      contrast to 61 and 66/10,000 diabetic individuals, indicating a 44 fold and 33
      fold excess risk of diabetic patients. CONCLUSION: It is concluded that these 2
      surveys 5 years apart reveal a failure of reducing lower extremity amputations in
      people with diabetes--despite the objectives of the St. Vincent-Declaration.

PMID- 9540427
TI  - Low-dose iloprost infusions compared to the standard dose in patients with
      peripheral arterial occlusive disease Fontaine stage IV. DAWID Study Group.
AB  - BACKGROUND: Intravenous iloprost, titrated from 0.5 up to 2.0 ng/kg/min has been
      shown in patients with PAOD III/IV to significantly improve healing of trophic
      lesions, relief of rest pain, and reduce the rate of major amputation or death at
      6 months as compared to placebo. The effect is considered related to improvement
      of the microcirculation. The aim of the present trial was to identify an optimum
      dose regarding treatment response and tolerability, by studying 4 doses of 25,
      50, 75 and 100 micrograms iloprost daily. PATIENTS AND METHODS: 302 patients with
      PAOD IV were randomised via a double-blind fashion to one of the 4 doses. The
      primary endpoint was the responder rate at end of treatment. Responders were
      defined as patients with very good or good global efficacy, as judged by lesion
      healing and pain relief. Side effects were documented and a pre-defined
      benefit/risk index was calculated. RESULTS: No dose-dependency of iloprost
      regarding primary or secondary endpoints was observed. The rate of responders
      ranged between 48.7-53.5%. Side effects, mainly related to vasodilation,
      increased dose-dependently (p < 0.001, chi 2-test), with a significant decrease
      of the benefit/risk index from 2.19 +/- 1.19 to 1.64 +/- 0.97 (p = 0.012, ANOVA).
      Responders had a better outcome at 6 months than non-responders (2.6 fold higher
      rate of major amputation or death; life table analysis). CONCLUSIONS: It is
      concluded that iloprost should be titrated to the optimum rather than maximum
      tolerated dose, since a higher incidence of side effects not associated with an
      increased treatment response was observed at higher doses.

PMID- 9540428
TI  - Recanalization of chronic peripheral arterial occlusions by alternating intra
      arterial rt-PA and PGE1.
AB  - BACKGROUND: Recanalization of femoral artery occlusions is difficult and
      different forms of intra-arterial lysis or mechanical procedures have been
      described. We investigated the effectiveness of a prolonged intra-arterial lysis
      with rt-pa in combination with PGE1 followed by angioplasty. PATIENTS AND
      METHODS: 43 patients (age 60.4 +/- 14.3 years) with peripheral arterial
      occlusions older than 3 months and longer than 10 cm were treated with intra
      arterial rt-pa (3 mg in 3 h) followed by PGE1 (2.1 ml/h for 3 h, concentration:
      20 micrograms/50 ml NaCl) in alternating order. Treatment times ranged from 1 to
      7 days (2.9 +/- 1.6). Doses of 26.5 +/- 21.9 mg rt-PA and 20.4 +/- 16 micrograms
      PGE1 were used. If necessary, angioplasty was performed after a wire was passed
      through the lumen. RESULTS: Recanalization was achieved in 47 out of 85 arterial
      segments with reocclusion in 9 segments. The arterial perfusion deteriorated once
      due to peripheral embolism. Other adverse effects included one case of
      retroperitoneal and one case of intracrural bleeding and one aneurysma spurium.
      CONCLUSION: In chronic arterial occlusions which do not respond to conventional
      angioplasty and/or short term fibrinolysis recanalization may be achieved in
      about 50% by means of prolonged alternating application of rt-pa and PGE1.

PMID- 9540429
TI  - Influence of the angiographic internal carotid artery stenosis assessment method
      on indicating carotid surgery.
AB  - BACKGROUND: To estimate the influence of different kinds of angiographic internal
      carotid artery (ICA) stenosis assessment methods on clinical decision making on
      carotid surgery. METHOD: One hundred angiographically proven ICA lesions in 65
      patients (54 men, 11 women, mean age +/- SD, 64 +/- 8 years) were evaluated by
      simultaneous biplane angiography. The angiograms were analyzed using three kinds
      of linear diameter reduction methods [North American (NASCET), and European
      (ECST) carotid surgery trial method, common carotid artery method (CC)], and five
      area reduction methods reflecting more accurately the anatomical degree of
      stenosis [squared NASCET, ECST and CC (N2, E2, CC2), combined stenosis estimation
      of two projections (NASCET-bi, ECST-bi)]. All lesions were additionally evaluated
      by continuous wave (cw-)Doppler ultrasound prior to angiography. Between method
      agreement on classifying the lesions into stenosis < 70% and into stenosis > or =
      70% was calculated by means of kappa statistic. RESULTS: The degree of stenosis
      (median and inter-quartile range) ranged between 65% (38-82) by means of NASCET
      and 91% (87-93) by means of CC2. Thirty-seven ICA stenoses would have been
      operated on using NASCET, but 82 using CC2. Between method agreement on assessing
      high grade ICA stenosis ranged from poor (kappa value 0.17 for the pair
      NASCET/CC2) to excellent (kappa value 0.92 for the pair N2/NASCET-bi). Cw-Doppler
      ultrasound showed a good agreement (kappa value 0.72-0.80) with all angiographic
      methods using an area reduction formula apart from CC2. The agreement was
      moderate between cw-Doppler and NASCET and ECST, respectively. CONCLUSION: The
      clinical decision to operate on an ICA stenosis will strongly be influenced by
      the angiographic method used. Because reliable clinical data exist only for the
      NASCET and ECST method these two angiographic stenosis assessment method should
      be used for clinical decision making.

PMID- 9540430
TI  - Abdominal aortic aneurysm surgery in octogenarians.
AB  - BACKGROUND: It is difficult to decide whether to operate on a symptomless,
      abdominal aortic aneurysm in an elderly person almost in the last decade of their
      life. PATIENTS AND METHODS: A comparative retrospective review was undertaken of
      77 octogenarians and 692 other patients aged less than 80 treated for infrarenal
      abdominal aortic aneurysms between January 1980 and July 1992 at the Department
      of Thoracic and Cardiovascular Surgery of Helsinki University Central Hospital,
      Finland. Of these 77 octogenarians, 60 underwent surgery and 17 were treated non
      surgically. Of the 60, 48 (80%), and 284 of the 692 (41%) non-octogenarians
      underwent emergency surgery either because of ruptured aneurysm (RAAA group: 35
      octogenarians and 213 non-octogenarians) or because of non-ruptured but impending
      rupture (NRAAA group: 13 octogenarians and 71 non-octogenarians). RESULTS:
      Emergency surgery was more frequent among octogenarians than among younger
      patients (p < 0.001) and was associated with significantly higher 30-day
      mortality rates in the RAAA group: 71% (22/35) versus 36% (76/213) (p < 0.01) and
      in the NRAAA group: 38% (5/13) versus 14% (10/71) (p < 0.05). Elective surgery
      for symptomless abdominal aortic aneurysms (AAA group) was associated with 8%
      (1/12) 30-day mortality rates in octogenarians and 8% (33/408) in non
      octogenarians. Survival rates for non-surgically treated symptomless
      octogenarians were statistically significantly lower (log rank test) than for
      electively treated octogenarians and for an age- and sex-matched Finnish
      population. Median survival for non-surgically treated octogenarians was 2.5
      years (SE 0.13), with 50% of the patients dying from rupture of their aneurysms
      during the follow-up period. CONCLUSION: These findings support the active
      treatment of abdominal aortic aneurysms on an elective basis among the elderly.

PMID- 9540431
TI  - Prevention of deep venous thrombosis associated with superficial thrombophlebitis
      of the leg by early saphenous vein ligation.
AB  - BACKGROUND: Thrombophlebitis of the superficial veins of the leg used to be
      regarded as a mild and uncomplicated disease, particularly in German speaking
      countries. PATIENTS AND METHODS: In a retrospective clinical study from 6/91
      until 12/96 we followed the progress of all patients (n = 398) with
      thrombophlebitis of the vena saphena magna or parva. Parameters of interest were:
      the incidence of concomitant deep vein thrombosis and subsequent pulmonary
      embolism. All patients underwent colour duplex scanning, most of them repeatedly.
      In cases of proven ascending superficial thrombosis, or involvement of the
      saphenofemoral junction, proximal saphenous vein ligation was performed (n = 56,
      49 vena saphena magna and 7 vena saphena parva). Among these groups, there were
      10 patients with malignant disease (18%), ten with a history of thrombosis (18%),
      another five comprised diabetes, recent major surgery and organ transplantation.
      RESULTS: In 56 operations we found free-floating thrombi 6x (11%), 19x the
      sapheno-femoral junction was involved (33%), 24x the saphenous vein close to the
      junction (43%). Three patients develop deep vein thrombosis, despite surgery
      (0.75% of all and 5% of the operated cases). 2 patients suffered from (non
      lethal) pulmonary embolism (0.5% and 3.5%, respectively). One embolism occurred
      before vein ligation. Perioperative morbidity amounted to 8.5% (superficial wound
      infection, hematoma). CONCLUSION: Venous ligation is probably effective in
      reducing the rate of fatal pulmonary embolism.

PMID- 9540432
TI  - Improvement of acral circulation in a patient with systemic sclerosis with
      stellate blocks.
AB  - We report on a 77-year-old male patient with systemic sclerosis. He suffered from
      secondary Raynaud's phenomenon on the basis of systemic sclerosis. Medical
      treatment in the past, including the administration of calcium-channel blockers,
      pentoxifylline and intravenous prostaglandin therapy, was unsuccessful and the
      clinical situation became worse. In a final effort stellate blocks were performed
      over a period of several weeks and, for the first time, there was lasting
      clinical benefit. Complaints and Raynaud's attacks abated significantly, as
      documented by local cold exposure tests. Therapeutic benefit from stellate blocks
      in a patient with systemic sclerosis is described here for the first time.

PMID- 9540433
TI  - [Arteriovenous fistula after endoscopic dissection of the perforant vein of the
      lower leg with the neodymium:YAG laser in chronic venous stasis syndrome].
AB  - The endoscopic dissection of the perforating veins has been invented by Hauer in
      the last decade. He introduced the videoendoscopy to this surgical procedure. The
      avoidance of operative access through areas of trophic changes is very beneficial
      for reducing postoperative complications. Although postoperative thermic lesion
      have been reported on. Following an endoscopic laser coagulation of a Cockett
      perforating vein an arterio-venous fistula between the posterior tibial artery
      and vein developed by the mechanism mentioned. Persisting pain and the
      persistence of the ulcer led to several diagnostic measures including
      phlebography, digital subtraction angiography and CT-scan. After the fistula had
      been closed successfully by percutaneous embolization with four platin wires the
      ulcer disappeared.

PMID- 9540434
TI  - Chylous reflux into the lower limb with septic shock successfully treated by
      resection of the retroperitoneal megalymphatics.
AB  - A 15-year-old boy with primary chylous reflux into the left lower limb with
      septic shock was successfully treated by en bloc resection and ligation of the
      retroperitoneal megalymphatics. The episode of chyle discharge from the lower
      limb and/or genitalia and the presence of small vesicles of the skin may be an
      important sign in diagnosing chylous reflux. Surgical interruption of the chylous
      reflux and reduction of girth may be needed.

PMID- 9540435
TI  - [Stent treatment of a false postoperative carotid aneurysm].
AB  - A 64-year old man developed an aneurysm at the distal anastomosis of a carotido
      carotid PTFE-interposition which was treated by placement of a stent.
      Angiographic and computertomographic follow-up examinations after 9 months
      demonstrated the complete disappearance of the aneurysm after implantation of a
      self-expanding uncovered stent (Wallstent).

PMID- 9540436
TI  - Cutaneous polyarteritis nodosa.
AB  - Here we present two characteristic cases of cutaneous polyarteritis nodosa
      (cutaneous PAN). Cutaneous PAN is characterized by a chronic relapsing benign
      course over many years. In its mild form it presents with live-do and multiple
      painful nodular skin lesions mainly of the legs. In its more severe form painful
      skin ulcerations occur that are often accompanied by discrete polyneuropathy.
      Progression to systemic PAN is the exception. Only the more severe kinds of
      cutaneous PAN require a low-dose immuno-suppression. Assessment and treatment of
      cutaneous PAN are discussed.

PMID- 9540437
TI  - [SieScape: a new dimension in ultrasound].

PMID- 9540438
TI  - Ambulatory and inpatient procedures in the United States, 1995.
AB  - OBJECTIVES: This report presents estimates of surgical and nonsurgical procedures
      performed in the United States during 1995. Data are presented by characteristics
      of patients, region of the country, and procedure categories for ambulatory and
      inpatient procedures separately and combined. METHODS: Estimates in this report
      are based on data collected from the National Hospital Discharge Survey (NHDS)
      and the National Survey of Ambulatory Surgery (NSAS). NHDS provides data on
      hospital inpatient care, and NSAS provides data on ambulatory surgery in
      hospitals and in freestanding ambulatory surgery centers. For NHDS, data were
      collected for approximately 263,000 discharges from 466 non-Federal short-stay
      hospitals (92 percent response rate). For NSAS, data were collected for
      approximately 122,000 ambulatory surgery discharges from 489 hospitals and
      freestanding ambulatory surgery centers (80 percent response rate). RESULTS: An
      estimated 69.2 million procedures were performed on 38.7 million discharges from
      hospitals and freestanding ambulatory surgery centers during 1995: 39.8 million
      procedures were for inpatients, and 29.4 million were for ambulatory patients.
      Females had more procedures than males, and the rate of procedures increased with
      age in ambulatory and inpatient settings. The leading procedures for ambulatory
      surgery patients and inpatients combined were endoscopy of small intestine,
      arteriography and angiocardiography, extraction of lens, and endoscopy of large
      intestine.

PMID- 9540439
TI  - Essential diabetes mellitus care guidelines. Prepared by the Wisconsin Diabetes
      Advisory Group.

PMID- 9540441
TI  - Diabetes guidelines: a message to the physician.

PMID- 9540440
TI  - Frequently asked questions about the essential diabetes mellitus care guidelines.

PMID- 9540442
TI  - Some thoughts on the current status of treatment for diabetes mellitus.

PMID- 9540443
TI  - The role of the diabetes educator.

PMID- 9540444
TI  - The new classification and diagnostic criteria for diabetes mellitus: rationale
      and implications.

PMID- 9540445
TI  - The prevalence of diagnosed diabetes among Wisconsin adults.

PMID- 9540446
TI  - Diabetes care management: a managed care approach.
AB  - A Diabetes Care Management program was developed by PrimeCare, a network model
      HMO, to improve quality of life health outcomes and reduce the costs of medical
      care for its members with diabetes. The HMO used a systems-based approach to
      communicate information about appropriate self-management and standards of care
      to members and physicians. The focus of the program was to educate and encourage
      patients to self-manage their illness, and to partner with physicians, other
      health care providers and community organizations to achieve improved quality of
      life, clinical and financial results. Clinical process indicators were used to
      measure results of interventions. Significant increases in the percentage of
      participants receiving glycosylated hemoglobin (HbA1c) tests, retinal eye exams
      and lipid panel tests were achieved.

PMID- 9540447
TI  - What is effective diabetes nutrition therapy and who is qualified to provide it?

PMID- 9540448
TI  - New guidelines challenge and energize diabetes health care providers.

PMID- 9540449
TI  - Physicians prepare for changes in treating diabetes.

PMID- 9540450
TI  - Diabetes mellitus: when it rains, it pours...

PMID- 9540451
TI  - Therapy for type 2 diabetes mellitus.
AB  - Type 2 diabetes mellitus is a common, chronic disease affecting nearly 6% of the
      adult US population. It remains a leading cause of morbidity and mortality in
      Wisconsin as well as the country. Multiple lines of evidence show that
      controlling blood glucose in patients with type 2 diabetes can significantly
      decrease the development of and/or progression of microvascular complications as
      well as the macrovascular complications of diabetes. There are now four different
      classes of oral medications which are available to treat diabetes-sulfonylureas,
      biguanides, thiazolidinediones, and alpha-glucosidase inhibitors. Each class
      works differently to treat the underlying defects of diabetes which include
      impaired insulin secretion, insulin resistance and exaggerated postprandial
      hyperglycemia. This article will compare and contrast the different agents
      available, including appropriate use of each agent as monotherapy and in
      combination therapy. It will also discuss use of insulin in the patient who has
      failed oral therapy. Rational use of these tools, tailored for the individuals
      metabolic abnormalities, should allow for good glycemic control in the majority
      of patients with type 2 diabetes mellitus. Relaxation, massage, opium, and
      moderate exercise were among the recommended options for treatment of diabetes
      mellitus nearly 100 years ago. In the late nineteenth century, diabetes was a
      poorly characterized disorder, which was increasing in prevalence even at that
      time. Today, the underlying defects contributing to the development of type 2
      diabetes are better understood, and include peripheral insulin resistance,
      relative pancreatic beta-cell insufficiency, increased hepatic glucose output,
      and an exaggerated postprandial glucose excursion. However, despite our better
      understanding of the disease, the prevalence of type 2 diabetes continues to
      increase in the US, now afflicting over 6% of the population. As our population
      ages and the proportion of obese people increases, we can expect to see a marked
      increase in the prevalence of diabetes in the future. Fortunately, our treatment
      options for type 2 diabetes have expanded remarkably within the last few years.
      Along with these new treatment options comes the exciting, although likely
      expensive, possibility of prevention of type 2 diabetes in at risk individuals.

PMID- 9540452
TI  - Age- and gender-adjusted comparison of Wisconsin native mortality with general
      Wisconsin population, for diabetes and diabetes-related causes of death--1986
      1995.
AB  - To compare mortality for diabetes and diabetes-related causes in Native American
      (NA) with total mortality for Wisconsin population by age, and gender. METHODS:
      Adjusting for age and sex, standardized mortality ratios (SMRs) were calculated
      for Wisconsin Native Americans for 1986-1995, using the 1990 total Wisconsin
      population as a reference and death certificate data to count and categorize
      deaths. RESULTS: Statistically significant high NA SMRs were found for total
      deaths (SMR = 1.28, p < .005), diabetes (SMR = 2.87, p < .005), heart disease
      (SMR = 1.16, p < .005), and kidney disease (SMR = 2.72, p < .005). There was
      substantial concordance in SMRs between men and women. NA SMRs were above 1 for
      all five year age groups below 75. Comparisons are provided with national data.
      CONCLUSION: Mortality due to diabetes mellitus, heart disease and kidney disease
      are higher among Native Americans in Wisconsin for all age groups below 75 and in
      both genders.

PMID- 9540453
TI  - Improving diabetes care for Medicare beneficiaries in outpatient setting: follow
      up report.

PMID- 9540454
TI  - Finally, HCFA proposes regulations interpreting stark II.

PMID- 9540455
TI  - Petasites hybridus: a tool for interdisciplinary research in phytotherapy.
AB  - The 3rd Petasites gathering took place in Romanshorn, Switzerland on March 29,
      1996 and gave 16 European scientists the opportunity to transmit their latest
      considerable discoveries to interested researchers working in different
      scientific disciplines such as pharmacognosy, botany, chemistry, pharmacology,
      medicine or clinical pharmacy. The newest findings on Petasites hybridus as a
      significant plant drug showed very promising aspects of therapeutic utility.
      Great progress has been made in chemical analytical methods and the determination
      of pharmacological activities. Substantial advances have also occurred in the
      production of bioassay procedures and plant materials, particularly utilizing
      cell- and tissue-culture techniques.

PMID- 9540456
TI  - Effect of film composition and various penetration enhancers concentrations on
      prazosin release from acrylic polymeric films.
AB  - An investigation was conducted to evaluate the effect of changing the Eudragit RL
      100 ratio and the influence of different penetration enhancers in various
      concentrations on the release of prazosin from Carboset 525:Eudragit RL 100
      polymeric films using improved Franz diffusion cells, to choose the most suitable
      polymeric film ratio, the most appropriate enhancer and its optimum concentration
      to be used to achieve the maximum release of the drug. The results show that
      prazosin release from polymeric films containing Carboset 525:Eudragit RL 100 in
      a 1:1 ratio was significantly (p < 0.05) higher than from films in a 1:0.25 ratio
      and non-significantly (p > 0.05) higher than from those containing 1:0.5, 1:3
      polymer ratios and non-significantly lower from those containing 1:4 polymer
      ratios. The addition of various enhancers, n-decyl alcohol (7, 9 and 11% w/w),
      Azone (4, 6 and 8% w/w) and Cineole (7, 9, 11 and 14% w/w) significantly (p <
      0.05) enhanced the prazosin release from these polymeric films containing the two
      polymers in a 1:1 ratio. The best concentrations of these enhancers were 11% n
      decyl alcohol, 9% Cineole and 8% Azone. The formulations containing these
      concentrations of the enhancers are being further studied for drug release
      through rabbits skin. It was found that using either of these enhancers in these
      concentrations resulted in a significant (p < 0.05) increase in the amount of
      prazosin transported across the skin. On the other hand these enhancers did not
      show any significant (p > 0.05) difference between them. The mechanism of drug
      release from the polymeric films was further studied using water vapor
      permeability (W.V.P.), the permeability constant (P) and differential scanning
      calorimetry. The enhancers were found to increase the W.V.P. and the permeability
      constant (P) and the results were in very good agreement with the effect of
      enhancers on the in-vitro drug release. The DSC thermograms showed that the
      enhancers physically interacted with either or both of the polymeric film
      materials and prazosin which could be one of the reasons for the improvement in
      the release of the drug from these polymeric films.

PMID- 9540457
TI  - Effect of coating of aluminum carboxymethylcellulose beads on the release and
      bioavailability of diclofenac sodium.
AB  - The production of spheres loaded with diclofenac sodium by the cross linking
      technique was achieved. The hydrophilic polymer sodium carboxymethylcellulose (Na
      CMC) which gels in the presence of a cross linking agent, aluminum chloride
      (AlCl3), was used as a matrix forming agent for the bead production. To obtain a
      regular and uniform rate of drug release, the produced beads were coated with
      sodium alginate to increase the pathway of the diffused medium. Two processing
      variables were studied, the flocculating agent concentration (20, 40 and 60% w/v)
      and different coating times (15, 30 and 60 min). The results show that the higher
      concentrations of aluminum chloride (40 and 60% w/v) produced more uniform and
      rounded beads than that prepared using 20% w/v salt. The particle size of the
      core beads decreased insignificantly (P > 0.05) as the flocculating agent
      concentration increased. The coating time did not affect the particle size of the
      coated beads within the same concentration of aluminum chloride. The dissolution
      studies showed that the release rate of diclofenac sodium from the core beads
      increased with the increase of AlCl3 concentration and that the rate of drug
      release was markedly reduced after the coating of the core beads with Na
      alginate. The results also show a linear relationship for drug release over a 4-5
      h period from the core beads where it showed a longer straight line relationship
      (7 h) for the coated beads. The coating of the Al-CMC beads, prepared using 60%
      w/v AlCl3.6H2O, with 2% w/v aqueous solution of Na-alginate resulted in a
      significant (P < 0.05) sustaining action of the Al-CMC beads as indicated by the
      shift in Tmax from 1.7 +/- 0.84 to 3 +/- 0.71 h and the prolongation of the MRT
      from 7.86 +/- 0.54 to 10.82 +/- 1.33 h. The Cmax increased significantly from
      5.43 +/- 2.91 to 11.66 +/- 6.18 micrograms/ml while the AUC0-->24 increased
      insignificantly (P > 0.05) from 39.82 +/- 26.61 to 57.92 +/- 25.58 micrograms
      h/ml resulting in a relative bioavailability of 145.45% relative to Al-CMC beads.

PMID- 9540458
TI  - In vitro studies of simulated percutaneous absorption: influence of various
      enhancers in the release of clonazepam from 2-hydroxyethyl acetate patches.
AB  - A diffusion cell with an artificial membrane and the single-pass perfused rabbit
      ear were used to evaluate the percutaneous absorption of clonazepam from various
      2-hydroxyethyl acetate (HEA) patches. The influence on drug permeation of the
      various type of enhancers (isopropylmyristate, lauryl alcohol, propylene glycol
      and water) in the patches was tested. A comparison between the two types of
      systems of percutaneous absorption of clonazepam has been done. The results
      showed that HEA patches produce controlled uniform drug release, modulated by the
      addition of enhancers.

PMID- 9540459
TI  - Construction of a model of the Candida albicans lanosterol 14-alpha-demethylase
      active site using the homology modelling technique.
AB  - On the basis of all hitherto known P450 X-ray structures and applying standard
      homology modelling procedures a three-dimensional model of the lanosterol-14
      alpha-demethylase active site was constructed. The modelled active site nicely
      hosts the natural substrate lanosterol and the substrate-enzyme complex displayed
      stability in a 70 ps molecular dynamics simulation. The importance of Thr 122 of
      lanosterol 14 alpha-demethylase for hydrogen bond formation with the 3-hydroxyl
      group of lanosterol was found to be a characteristic feature of the interaction
      geometry.

PMID- 9540461
TI  - Synthesis of some 3-arylamino-5-aryloxymethyl[1,2,4]triazole derivatives and
      their antimicrobial activity.
AB  - In this study, some 3-arylamino-5-aryloxymethyl[1,2,4]triazole derivatives were
      synthesized by reacting S-methyl-N'-arylisothiouronium iodide and 2
      (aryloxy)alkanoic acid hydrazide. The structural elucidation of the compounds was
      performed by IR, 1H-NMR and MS spectroscopic data and elemental analyses results.
      Antibacterial and antifungal activities of the compounds were examined.

PMID- 9540460
TI  - Amide derivatives with H1-antihistaminic effect.
AB  - The synthesis and the structure-activity correlation of a series of N
      aminoalkylacetamides as H1-antihistaminic agents have been carried out. The
      compounds were tested in vitro by measurement of the inhibition of histamine
      induced contractions on isolated guinea pig ileum; the results are expressed as
      pA2.

PMID- 9540462
TI  - Equipping the complete dental practice. Interview by Phillip Bonner.

PMID- 9540463
TI  - Optimum dentures, Part 4: A perspective on vertical and centric relationships.

PMID- 9540464
TI  - Occlusal Glass veneers: adjustable and kind.

PMID- 9540465
TI  - The art of endodontics: cleaning and shaping the root canal system. The apical
      preparation. Part IV of a four-part series on cleaning and shaping root canals.

PMID- 9540466
TI  - Post-operative maintenance of aesthetic restorations: a plaque control concern.

PMID- 9540468
TI  - Sorry, our computer is down! Part 2: Understanding software.

PMID- 9540467
TI  - Disinfectants: do they work equally well?

PMID- 9540469
TI  - How to choose a periodontal patient management program.

PMID- 9540470
TI  - The rewards of change. Efficient doctor/hygiene examinations.

PMID- 9540471
TI  - More frequent dental visits prescribed for children with AIDS.

PMID- 9540472
TI  - Update on dental implants. Interview by Phillip Bonner.

PMID- 9540473
TI  - Computer-assisted implant planning and presentation.

PMID- 9540474
TI  - Root resection and retrofill: defining objectives to achieve surgical success.

PMID- 9540475
TI  - A welcome addition to an armamentarium.

PMID- 9540476
TI  - Internal bonding of the cracked tooth syndrome.

PMID- 9540477
TI  - A transitional treatment.

PMID- 9540478
TI  - Videographic diagnosis of pit and fissure caries.

PMID- 9540479
TI  - Cosmetic and reconstructive therapy.

PMID- 9540480
TI  - The value of self-esteem in treatment presentation.

PMID- 9540481
TI  - Pharmacological management of dental pain: an interview with Dr. Peter L.
      Jacobsen. Interview by Phillip Bonner.

PMID- 9540482
TI  - The art of endodontics: pain management techniques.

PMID- 9540483
TI  - A peek at palates.

PMID- 9540484
TI  - 'Growing' enamel.

PMID- 9540485
TI  - Achieving optimal aesthetics through bone grafting.

PMID- 9540486
TI  - The maxillary anterior porcelain crown: ingredients for optimum aesthetics, Part
      2.

PMID- 9540487
TI  - What to do about post-extraction bleeding.

PMID- 9540488
TI  - E-anesthesia: pulp fiction or virtual reality.

PMID- 9540489
TI  - "I need to talk to you about a raise".

PMID- 9540490
TI  - Reaping the benefits of marketing quality.

PMID- 9540491
TI  - Provisional restorations in anterior procedures.

PMID- 9540492
TI  - Multiple cantilevers: an alternative to dental implants.
AB  - A solution to the problem of missing posterior teeth is presented. The
      prerequisite for solving this problem is that the remaining teeth must be
      positioned in one form or another in a triangle, as one can see in Figs. 2, 3 and
      4. The tripod effect, in connection with the controlling effect of the mechano
      receptors in the periodontal ligaments of the remaining abutment teeth, permit us
      to construct a functional fixed prosthesis. The feather-edged or knife-edged
      preparation technique creates long axial walls. Together with the parallel
      prepared abutment teeth, this must be viewed as the main-retentive feature for
      fixed prostheses with multiple cantilevers. In extreme situations, where one is
      uncertain about the outcome of a case, provisional laboratory fabricated
      restorations are excellent for evaluating the stability of the cross-arch
      splinted teeth. The whole bridge occasionally shows some mobility. As long as the
      mobility shows no increase over a period of time, and does not interfere with the
      patient's chewing ability, a permanent bridge with multiple cantilevers can be
      inserted. I usually include no more than three cantilevered pontics on each side
      of the arch in a multiple cantilevered bridge. A second molar is not replaced by
      a third cantilevered pontic. Its position in the arch may cause an overly strong
      lever action on the fixed prosthesis.

PMID- 9540493
TI  - Removable prosthodontics vital to dentistry. An exclusive interview with Dr. Jack
      Turbyfill. Interview by Phillip Bonner.

PMID- 9540494
TI  - Endodontic retreatment: when and how.

PMID- 9540495
TI  - Enhanced and super-enhanced root planing.

PMID- 9540497
TI  - Periodontal team management, Part 3.

PMID- 9540496
TI  - Combining techniques for an aesthetic result.

PMID- 9540498
TI  - Should a dental lab practice infection control?

PMID- 9540499
TI  - Total quality records: how to create the perfect patient chart.

PMID- 9540500
TI  - A turn-of-the-century practice.

PMID- 9540501
TI  - Risk! Investment measurement tools.

PMID- 9540502
TI  - Update on pain management in dentistry: an exclusive interview with Dr. Stanton
      Wolfe. Interview by Phillip Bonner.

PMID- 9540503
TI  - Antibiotic therapy: maximize the benefits, minimize the risks.

PMID- 9540504
TI  - Preservative cosmetic dentistry.

PMID- 9540505
TI  - Creative aesthetic treatment options: a case study.

PMID- 9540506
TI  - Fluoride: an update for the year 2000, Part 2.

PMID- 9540507
TI  - Dental iatrogenesis.

PMID- 9540508
TI  - The endodontic restorative convergence: genesis, synthesis, and hypothesis.

PMID- 9540509
TI  - Periodontal plastic surgery, Part 2.

PMID- 9540510
TI  - Pellicle-removing dentifrice found to control chlorhexidine stains.

PMID- 9540511
TI  - Post-dated checks and collections calls: keeping them legal.

PMID- 9540512
TI  - Private dental insurance trends in the U.S.

PMID- 9540513
TI  - Update on office safety. Interview by Phillip Bonner.

PMID- 9540514
TI  - Implant rehabilitation of mandibular posterior edentulous quadrants.

PMID- 9540515
TI  - Endodontic diagnosis, Part 2: Pulp tests.

PMID- 9540516
TI  - Root resection and retrofill: defining objectives to achieve surgical success,
      Part III.
AB  - Fortunately, medical contraindications to root resection and retrofill are rare.
      Although when present, some contraindications are potentially life threatening or
      involve significant possible morbidity. The value of consultation with the
      treating physician obtaining a complete and thorough medical history and proper
      modification and management of medical conditions to facilitate surgical
      endodontic therapy cannot be stressed enough for the most predictably successful
      treatment.

PMID- 9540517
TI  - Benefit-driven treatment planning.

PMID- 9540518
TI  - Inexpensive high-quality full-face patient photographs.
AB  - Although even the simplest arrangement for taking extraoral patient photographs
      is better than no procedure at all, the most practical and efficient solution is
      to invest in a setup that includes an extraoral camera with electronic dual flash
      and backdrop screen. Once the components have been set up, and the optimal
      parameters established, the system is always ready, and taking the pictures is
      just a snap away. The studio quality of the photographs from this arrangement
      will provide invaluable contributions to the success of your cosmetic dental
      practice.

PMID- 9540519
TI  - Rebuilding the worn or broken down dentition.

PMID- 9540520
TI  - Treatment planning for prosthetics using guided bone regeneration.

PMID- 9540521
TI  - Summary of accounts receivable management.

PMID- 9540522
TI  - Flourishing in a non-insurance environment.

PMID- 9540523
TI  - Clean up your records with SOAP. S (subjective findings), O (objective findings),
      A (assessment), P (plan).

PMID- 9540524
TI  - Update on infection control: an exclusive interview with Dr. John A. Molinari.
      Interview by Phillip Bonner.

PMID- 9540525
TI  - Obturation materials and techniques: fact and fiction.

PMID- 9540527
TI  - A step-by-step approach to finishing porcelain veneers.

PMID- 9540526
TI  - Why overdentures?

PMID- 9540528
TI  - Building a successful cosmetic dental practice.

PMID- 9540529
TI  - How to get started in dental special effects.

PMID- 9540531
TI  - A complete guide to instant dental photography.

PMID- 9540532
TI  - Managing periodontal team management, Part 4.

PMID- 9540530
TI  - The myth of the paperless office: finding the real payoffs in information
      technology.

PMID- 9540533
TI  - Regaining control: the cold war between overempowered employees and practice
      owners.

PMID- 9540534
TI  - Motivating delinquent patients to bring their accounts current.

PMID- 9540535
TI  - Managed communications in a managed care future.

PMID- 9540536
TI  - HIV inhibitor identified in saliva.

PMID- 9540537
TI  - Dental materials roundtable.

PMID- 9540538
TI  - The hybrid bridge.

PMID- 9540539
TI  - A look at lips.

PMID- 9540540
TI  - Treating myofascial pain dysfunction syndrome using disclusion time reduction.

PMID- 9540541
TI  - Single-tooth implant aesthetics.

PMID- 9540542
TI  - Use of acetate transfer-enhanced stents in implant diagnosis and treatment.

PMID- 9540543
TI  - Million-dollar files: adding up the benefits of computerized patient records.

PMID- 9540544
TI  - Balancing a hygiene department for patient satisfaction and profits.

PMID- 9540545
TI  - The collection attitude: working out to be a champion.

PMID- 9540547
TI  - Peace of mind, part 2: Positioning your office and services.

PMID- 9540546
TI  - Working with a spouse.

PMID- 9540548
TI  - The future direction of dentistry: an exclusive interview with Dr. Omer Reed.
      Interview by Philip Bonner.

PMID- 9540549
TI  - Endodontic canal preparation: breakthrough cleaning and shaping strategies.
AB  - It could be said that cleaning and shaping is a game and, as such, can be played
      at various skill levels producing a range of endodontic results. Breakthrough
      cleaning and shaping strategies elevate the level of play by creating clean
      preparations that have been designed, sculpted, and shaped to flow and grace
      within. Excellence in canal preparations is an opening for packing the root canal
      system in three dimensions and increases the possibility of generating successful
      outcomes. Visualizing and executing great play moves the clinician toward mastery
      and winning the inner game of endodontics.

PMID- 9540551
TI  - A step-by-step approach to consistent vital tooth bleaching.

PMID- 9540550
TI  - Restoring endodontically treated teeth.

PMID- 9540552
TI  - Optimum dentures: Part 5. Helpful hints and 'C.A. factor'. Caring attitude
      factor.

PMID- 9540553
TI  - Solving crown and bridge problems with the combined bite impression technique.

PMID- 9540554
TI  - Practical adhesive dentistry.

PMID- 9540555
TI  - Osseointegration: the cause of or the cure for the complexity of prosthetic
      restoration of dental implants.

PMID- 9540556
TI  - Instant filmless radiology: changing the way dentists see.

PMID- 9540557
TI  - The rewards of change. Reactivating, restoring, and renewing relationships.

PMID- 9540558
TI  - Keeping your profits up with 'belt & suspenders' strategies.

PMID- 9540559
TI  - Where's the cash?

PMID- 9540560
TI  - Creating a demand for excellence by asking questions: a major step in case
      acceptance.

PMID- 9540562
TI  - Overcoming the challenge of anterior maxillary alveolotomies.

PMID- 9540561
TI  - The hybrid crown.
AB  - A crown type has been described that offers the advantages of both ceramic
      veneers and metal crowns. More than 200 single crowns and three three-unit
      bridges of this type have been inserted with no failures after two years.
      University-based shear and compressive testing is currently being arranged to
      affirm perceived clinical strength of this new crown type. Comparison testing
      also will be performed with comparative values for the hybrid crown, all ceramic
      (various types), and porcelain-fused-to-metal.

PMID- 9540563
TI  - Surgical techniques for a winning smile.

PMID- 9540564
TI  - The end of an era. An interview with Dr. Harald Loe. Interview by Phillip Bonner.

PMID- 9540565
TI  - Dental implants in combination with natural tooth abutments.

PMID- 9540566
TI  - Inferior approach to sinus elevations with sub-antral bone augmentations.

PMID- 9540567
TI  - New directions in implant technology.

PMID- 9540568
TI  - Debate continues over use of disposable handpieces. Interview by Lisa Rotella.

PMID- 9540569
TI  - Periodontal team management.

PMID- 9540570
TI  - Enhance scheduling: give the patient a reason to come back.

PMID- 9540571
TI  - Various features of managed care practices.

PMID- 9540572
TI  - Telephones are a practice's best friend.

PMID- 9540573
TI  - A marketing plan: your patient's perception.

PMID- 9540574
TI  - Fiber-enhanced periodontal therapy: an era of ultra-enhancement.

PMID- 9540575
TI  - Update on periodontics: an exclusive interview with Dr. Jon B. Suzuki. Interview
      by Phillip Bonner.

PMID- 9540576
TI  - Fluoride: an update for the year 2000.

PMID- 9540577
TI  - Periodontal plastic surgery.

PMID- 9540578
TI  - Wide-diameter implants: overcoming problems.

PMID- 9540579
TI  - A non-traumatic technique for removing melanotic pigmentation lesions from the
      gingiva: gingiabrasion.

PMID- 9540580
TI  - The continuous wave of condensation technique: a convergence of conceptual and
      procedural advances in obturation.

PMID- 9540581
TI  - Electrosurgery, bridgework and veneers make a new smile almost worth the wait.

PMID- 9540582
TI  - Treatment of recurrent oral aphthous and herpetic ulcerations.

PMID- 9540583
TI  - The flexible aesthetic post.

PMID- 9540584
TI  - Periodontal splinting alternatives or periodontal splinting with flexible ceramic
      bonding.

PMID- 9540585
TI  - Predictable crown and bridge with core build-ups.

PMID- 9540586
TI  - Insurance goes electronic.

PMID- 9540587
TI  - TB being viewed as leading killer of HIV-positive people.

PMID- 9540588
TI  - On-line consulting: a direct route to better dentistry. Interview by Cheryl Farr.

PMID- 9540589
TI  - Managing dental trauma. Interview by Phillip Bonner.

PMID- 9540590
TI  - The maxillary anterior porcelain crown: ingredients for optimum aesthetics.

PMID- 9540591
TI  - Conquering space, Part II: the crowded dentition.

PMID- 9540592
TI  - Aesthetic provisionals for porcelain veneers.

PMID- 9540593
TI  - A panoramic overview of Class II posterior composite resin placement techniques.

PMID- 9540594
TI  - The team approach to implant dentistry. Case presentation.

PMID- 9540595
TI  - Moving teeth with light force and ribbon brackets.

PMID- 9540597
TI  - That gray area of disease and treatment: what do we do?

PMID- 9540596
TI  - Expanding dental practices with computer technology.

PMID- 9540598
TI  - Consistent patient care: the secret to long-term relationships.
AB  - Consistent patient care is vitally important. While first impressions may appear
      to be the most important, they merely act as a bridge to get patients over to
      your side. Once they have crossed over, you must shift your focus to sustaining
      their loyalty by cultivating a desire for them to continue doing business with
      you. Practices who are committed to consistently meeting their patients' needs,
      and take the time to understand their patients as people--before, during and
      after patient care--ultimately keep their patients returning and referring for
      many years to come.

PMID- 9540599
TI  - Twenty-one major time management frustrations.

PMID- 9540600
TI  - Anterior apicos in general practice: step-by-step guidelines.
AB  - Apicoectomy and retroseal procedures should continue to be a mainstay of dental
      treatment because not all root canal therapy is successful, even when it is
      amenable to retreatment. Currently accepted methods for performing this operation
      have been reviewed. With appropriate case selection and the careful
      implementation of these techniques, the general dentist can confidently provide
      this service to patients.

PMID- 9540601
TI  - The shape of things to come.

PMID- 9540602
TI  - Endodontic perforation repair: using the surgical operating microscope.

PMID- 9540603
TI  - Update on endodontics: an exclusive interview with James L. Gutmann, DDS.
      Interview by Phillip Bonner.

PMID- 9540604
TI  - Intentional replantation: an alternative to extraction of an endodontic failure.

PMID- 9540605
TI  - The smile lift: a new concept in aesthetic care, Part 2.

PMID- 9540606
TI  - Cosmetic consultation and treatment.

PMID- 9540607
TI  - Bleaching and porcelain veneers: consider the combination.

PMID- 9540608
TI  - Restoration of a cervical lesion: etiology and factors affecting technique.

PMID- 9540609
TI  - Opening bite, replacing worn tooth: a 30-month follow-up.

PMID- 9540610
TI  - Integrated systems: dental technology comes of age.

PMID- 9540611
TI  - A proactive marketing opportunity for your practice.

PMID- 9540612
TI  - Managing the periodontal team.

PMID- 9540613
TI  - Keeping your practice's financial engine running.

PMID- 9540614
TI  - MB2 root canal systems in maxillary first molars.

PMID- 9540615
TI  - Gutta percha conefitting into tapered preparations: standardizing the use of non
      standard points.

PMID- 9540616
TI  - Endodontic re-engineering: effecting biologic closure.

PMID- 9540617
TI  - Endodontics and the law: an interview with Dr. Stephen Schwartz. Interview by
      Phillip Bonner.

PMID- 9540618
TI  - Building a better case presentation.

PMID- 9540619
TI  - Restoring the severely worn dentition: considerations and a step-by-step
      technique.

PMID- 9540620
TI  - Immediate bridgework can ease the pain of removing unwanted teeth.

PMID- 9540622
TI  - The art of building a high-profile celebrity practice.

PMID- 9540623
TI  - Uncovering early gum disease.

PMID- 9540621
TI  - Smile architecture: beyond smile design.
AB  - Successful cosmetic dental treatment is both functional and aesthetic. It
      requires evaluation of a patient's expectations, diagnosis of pre-existing
      problems and careful planning of treatment to eliminate or control the causes of
      existing conditions. The use of mounted diagnostic casts and a diagnostic wax-up
      allows visualization of the expected result. Provisional restorations offer a
      "dress rehearsal" to preview functional and aesthetic results before completion
      of the final restorations. The term "smile architecture" is used to describe the
      process that guides a patient and dentist from initial complaint through to final
      case acceptance.

PMID- 9540624
TI  - Redefining terms for better communication, treatment acceptance.

PMID- 9540625
TI  - Who trained your receptionist?

PMID- 9540626
TI  - Collection agencies, credit bureaus and other collection professionals.

PMID- 9540627
TI  - Your facility in the future may mean your future.

PMID- 9540628
TI  - Clinical determination of the posterior palatal seal.

PMID- 9540629
TI  - Streamlining single crown technique: preparation and impression.

PMID- 9540630
TI  - Occlusion: the foundation of restorative dentistry an interview with Dr. Mark S.
      Wolff. Interview by Phillip Bonner.

PMID- 9540632
TI  - Endodontic diagnosis: confidence from methodical skepticism, Part 1.

PMID- 9540631
TI  - Biopsy issues and procedures.

PMID- 9540633
TI  - Future directions in periodontics.

PMID- 9540634
TI  - Periodontics and restorative dentistry: when good doesn't look good enough.

PMID- 9540635
TI  - Selecting anterior crowns.

PMID- 9540636
TI  - Re-engineering the dental practice. Interview by Cheryl Farr.

PMID- 9540637
TI  - Instrument system organization in dental practice.

PMID- 9540638
TI  - Hygiene support, be responsible for your schedule.

PMID- 9540639
TI  - When all else fails: firing a patient.

PMID- 9540640
TI  - Minimizing broken appointments and no-shows.

PMID- 9540641
TI  - Healthcare reform in dentistry.

PMID- 9540642
TI  - Four steps to soft tissue management: non-surgical periodontal therapy.
AB  - Soft tissue management or nonsurgical periodontal therapy is based upon the
      current concepts of the dental plaque and the nature of periodontal disease
      progression. It is the initial step in the management of adult periodontitis and
      in those patients who, for what ever reasons, do not wish surgery, it is an
      excellent second choice of therapy. STM can be done by the general dentist and/or
      the hygienist. When done properly with the appropriate use of ultrasonics,
      antibiotics, irrigation (in the office and the home) and regular recalls to the
      dentist, it can produce marked improvement in the periodontal health of the
      patients and can be a very rewarding experience for the dentist and the
      hygienist, and above all the patient.

PMID- 9540643
TI  - Update on periodontics. Interview with Drs. Robert Genco and Mark Zablotsky.
      Interview by Phillip Bonner.

PMID- 9540644
TI  - Controlling forces on dental implants.

PMID- 9540645
TI  - From subperiosteal to osseointegration: an unusual demand met by an unusual
      approach.

PMID- 9540646
TI  - Predictable exodontia in general practice.
AB  - Exodontia that is carefully and skillfully done by general dentists is a valuable
      service to patients. The majority of patients would rather have their family
      dentist perform necessary extractions or other minor surgery procedures than be
      referred outside the office. Most teeth that need to be extracted could be
      removed by a generalist if that person has developed the expertise to do not only
      relatively easy extractions, but also that percentage that is inevitably more
      difficult--requiring "surgical" removal. To be successful with exodontia, the
      dentist must have the ability to select cases within his or her level of comfort
      and ability, have a working knowledge of sound surgical principles, be able to
      apply a variety of patient management techniques, and then be prepared to handle
      whatever complications may arise. This article has presented ideas that should be
      integrated into the operator's own systematic approach to extractions. It is one
      of many resources to help the general dentist provide a higher level of surgical
      treatment.

PMID- 9540647
TI  - A simplified technique for ridge preservation after tooth extraction.

PMID- 9540648
TI  - How to design smile styles for cosmetic dentistry.
AB  - Even though many patients may simply let you choose a smile style for them, once
      you select it, show it to them for their approval. As Jennifer de St. Georges
      says, "Inform before you perform. No surprises!" On the other hand, when patients
      offer verbal descriptions of how they want their smiles to look, there is a lot
      of room for subjective interpretation. By using photographs and models, much of
      the confusion can be eliminated. After all, our goal is to make the patient
      smile.

PMID- 9540649
TI  - The clinical use of objective electronic measurement in TMD.

PMID- 9540650
TI  - A panoramic overview of Class II posterior composite resin placement techniques,
      Part 2.

PMID- 9540651
TI  - Smarter perio: new technologies add intelligence, speed and accuracy to diagnosis
      and treatment. Interview by Cheryl Farr.

PMID- 9540653
TI  - Instrument circulation, Part 1.

PMID- 9540652
TI  - Just another toothpaste? Not anymore.

PMID- 9540654
TI  - Building the foundation for improved time management.

PMID- 9540655
TI  - Strategic planning for the professional practice.

PMID- 9540656
TI  - Plastic surgery without a scalpel.

PMID- 9540657
TI  - The coming of age of porcelain veneers.

PMID- 9540658
TI  - Pressed ceramic restorations.

PMID- 9540659
TI  - What will it look like?

PMID- 9540660
TI  - Integrating cosmetic dentistry into your practice.

PMID- 9540661
TI  - The smile lift: a new concept in aesthetic care, Part 1.

PMID- 9540662
TI  - The winning combination: orthodontics and cosmedontics.

PMID- 9540663
TI  - Cleaning and shaping the root canal system: negotiating canals to the termini.

PMID- 9540664
TI  - Predictably successful endodontics: the thermosoftened millennium.

PMID- 9540665
TI  - Hard technology for soft tissue.

PMID- 9540666
TI  - Optimum treatment based on decision tree-analysis, Part 2.

PMID- 9540667
TI  - The impact of President Clinton's plan on dentistry: an exclusive interview with
      Dr. Sheila McGuire. Interview by Phillip Bonner.

PMID- 9540668
TI  - Achieving optimal productivity with an intraoral camera.

PMID- 9540669
TI  - Making team meetings work.

PMID- 9540670
TI  - Using innovative technology to educate patients.

PMID- 9540671
TI  - Monitoring the financial health of a practice.

PMID- 9540672
TI  - Update on porcelain veneers: an exclusive interview with Dr. Mark Friedman.
      Interview by Phillip Bonner.

PMID- 9540673
TI  - Ultraconservative rehabilitation.

PMID- 9540674
TI  - Real teeth wear pink.

PMID- 9540675
TI  - Crowns, veneers, and temporaries: restoring a porcelain damaged dentition.

PMID- 9540676
TI  - Matching single-ceramic restorations to the existing dentition.

PMID- 9540677
TI  - A case presentation that sold me.

PMID- 9540678
TI  - Root resection and retrofill: defining objectives to achieve surgical success,
      Part I.

PMID- 9540679
TI  - Successful full-mouth reconstruction with laboratory-fabricated provisionals.

PMID- 9540680
TI  - Periodontal instrumentation.

PMID- 9540681
TI  - Controlling shrinkage using TEP: trans-enamel polymerization.

PMID- 9540682
TI  - Adhesives and air abrasion.

PMID- 9540683
TI  - Preventing, identifying and correcting indoor air quality problems.

PMID- 9540684
TI  - The 'C' word: continuity.

PMID- 9540685
TI  - I want on the information superhighway, but I'm riding a rickshaw that's stuck in
      the mud.

PMID- 9540686
TI  - Taking collections the extra mile.

PMID- 9540687
TI  - Keeping the old and attracting the new.

PMID- 9540688
TI  - Psychological effects of manmade disasters. A transcribed lecture.

PMID- 9540689
TI  - Tumors of minor salivary glands and the analysis of 106 cases.
AB  - This study is based on 106 cases of predominantly minor salivary gland tumors
      which were received at the University of Oklahoma College of Dentistry Department
      of Oral Pathology Biopsy Service from 1972 to 1995. (In this study), 55% of the
      cases were benign and 45% were malignant. Benign tumors include pleomorphic
      adenoma (68%), monomorphic adenoma (10%), oncocytoma/oncocytosis (7%), papillary
      cystadenoma (14%), and myoepithelioma (2%). Of the malignant tumors, 34% were
      mucoepidermoid carcinoma, 17% adenoid cystic carcinoma, 21% adenocarcinoma, not
      otherwise specified (N.O.S.), 21% polymorphous low-grade adenocarcinoma, and 6%
      malignant mixed tumors. There was no difference in relative incidence of benign
      or malignant tumors between males and females. The 7th decade was the peak
      occurrence age for both benign and malignant and the palate was the most frequent
      location.

PMID- 9540690
TI  - Team building/self esteem building.

PMID- 9540691
TI  - The effectiveness of sterilizing dental air-water syringes.

PMID- 9540692
TI  - The Indian Health Service in Oklahoma: dental service for American Indians.
AB  - The Indian Health Service has been providing dental services to American Indians
      in Oklahoma for more than 40 years. The dental program is part of an integrated
      health care delivery system that is one of the oldest examples of a staff model
      Health Maintenance Organization (HMO).

PMID- 9540693
TI  - What's new in endodontics?

PMID- 9540694
TI  - Restoring endodontically treated teeth. Alternatives to fixed prosthodontics.

PMID- 9540695
TI  - Dental ethics.

PMID- 9540696
TI  - Ishmael Essay Award winner. Infection control and the extent of contamination of
      dental charts.
AB  - The associations between dental charts and the probability of cross-contamination
      were examined by swabbing contaminated charts and plating the specimens on agar
      medium to be analyzed. Laboratory analysis of the agar plates revealed, that out
      of the twenty-one charts tested, fifteen were positive for bacterial growth,
      therefore, contaminated charts are a viable vector for cross-contamination.
      Further barrier techniques need to be implemented, which in turn would decrease
      the contamination potential for the spread of infection.

PMID- 9540697
TI  - The status of dental implants in Oklahoma.

PMID- 9540698
TI  - Coping with cracked tooth syndrome.
AB  - Cracked tooth syndrome typically poses a diagnostic challenge for the dentist.
      Symptoms include tenderness to biting on certain foods, often poorly localized,
      and occasional thermal sensitivity. Knowing where to look for this entity,
      especially in the mandibular molar region, can be especially helpful. Treatment
      of the tooth depends on the degree of pulpal involvement and the extent of the
      crack. Cuspal coverage is required of all cracked posterior teeth that are
      retainable. Root canal therapy is included if symptoms persist or if pulpal
      pathosis exists at the outset. Cracks extending beyond the osseous crest indicate
      a poor prognosis. Armed with this knowledge, the dentist can overcome many
      cracked tooth dilemmas, resulting in satisfaction for both patient and
      practitioner alike.

PMID- 9540699
TI  - The expert witness.
AB  - More and more, dentists are being asked to be involved in medical-legal
      proceedings. The criteria for being an expert is based upon education, training,
      and experience, all of which every licensed practicing dentist possesses. Dental
      record-keeping and unbiased, thorough case analysis are the important factor
      involved in medical-legal litigation.

PMID- 9540700
TI  - Resin-modified glass ionomers: a new option in restorative dentistry.
AB  - New dental materials and products are constantly being introduced in hopes of
      replacing or improving established materials. Although this onslaught of dental
      innovation can eventually lead to major improvements in the ease and success of
      clinical dentistry, it also presents a nightmare for the practitioner wishing to
      keep pace with these products. The introduction of the resin-modified glass
      ionomers at first glance appears to offer some very promising applications. Only
      time and clinical trials will give practitioners a true account of their benefits
      as well as their shortcomings.

PMID- 9540701
TI  - Forensic dentistry. Overview of forensic dentistry.

PMID- 9540702
TI  - Forensic dentistry. Beyond recognition.

PMID- 9540703
TI  - Forensic dentistry. Recognizing the signs and symptoms of domestic violence: a
      guide for dentists.
AB  - Non-accidental trauma (NAT) is a leading cause of death and injury in America.
      Women and elderly persons are much more likely to be injured by a family member
      or by someone known to them than by any other individual. This aggressive,
      violent behavior directed against an individual within the home or family has
      been defined as "domestic violence." Intrafamily violence effects one in two
      American families and occurs in all segments of society. Studies have shown that
      unless intervention occurs, the violence tends to escalate often resulting in
      serious injury or death. Because greater than half of all domestic violence
      injuries occur in the head and neck area, the dentist is often the first to treat
      the domestic violence victim. Each member of the dental team must be a
      participant in the early recognition of domestic violence and other forms of non
      accidental trauma. Intervention can only begin after the victim is recognized.
      While acknowledging the important role of the forensic odontologist in the
      diagnosis and documentation of intentionally inflicted injuries, the general
      dentist and the dental team play an equally important role in stopping domestic
      violence.

PMID- 9540704
TI  - Forensic dentistry. Documentation of bite-mark evidence using multiple computer
      assisted techniques.

PMID- 9540705
TI  - Forensic dentistry. Civil litigation and the narrative report.

PMID- 9540706
TI  - How will managed care affect dentistry?

PMID- 9540707
TI  - Review of metronidazole use in dentistry.

PMID- 9540708
TI  - Advanced imaging techniques assist in implant planning.

PMID- 9540709
TI  - A clinico-pathologic presentation. Congenital epulis of the newborn.

PMID- 9540710
TI  - Dental ethics and treating your family.

PMID- 9540711
TI  - Responding to attorney requests for patient information.

PMID- 9540712
TI  - The relation between smoking and periodontal disease.

PMID- 9540713
TI  - Alfred Einhorn: the discoverer of procaine.

PMID- 9540714
TI  - A clinico-pathologic presentation. Benign mucous membrane pemphigoid.

PMID- 9540715
TI  - Observe safeguards when terminating the dentist-patient relationship.

PMID- 9540716
TI  - Buying right.

PMID- 9540718
TI  - A new treatment may alleviate the effects of dry mouth.

PMID- 9540717
TI  - Avoiding the stress of staff turnover.

PMID- 9540719
TI  - The great Morton-Jackson debate.

PMID- 9540720
TI  - Detecting child abuse.

PMID- 9540721
TI  - Developing a cable access television show.

PMID- 9540722
TI  - A clinico-pathologic presentation. Lymphangioma.

PMID- 9540723
TI  - Handling staff compensation fairly.

PMID- 9540724
TI  - Tobacco control practices: how do Massachusetts dentists compare with dentists
      nationwide?

PMID- 9540725
TI  - Dental office interventions are essential for smoking cessation.
AB  - Cigarette smoking has a major impact both on oral health and general systemic
      health. Because up to 70 percent of smokers see their dentists each year, the
      dentist is in a very powerful position to intervene with the smokers to help them
      stop smoking. I have suggested a four-step program for assisting patients to
      quit, based on the National Cancer Institute's suggested protocol for the dental
      office, which uses techniques shown in clinical trials to be effective for
      helping smokers quit. The core of the NCI program involves identifying smokers,
      advising them to quit, providing assistance to patients trying to quit, and
      following-up on patients as a means of enhancing success rates. Dentists who
      implement an effective smoking cessation program in their practices can expect to
      achieve quit rates up to 10 to 15 percent each year among their patients who
      smoke. Such a rate of success, if established nationwide and continued over a
      period of years, would markedly reduce the prevalence of smoking in the United
      States.

PMID- 9540726
TI  - Study finds a correlation between smoking and tooth loss.

PMID- 9540727
TI  - Tobacco use assessment is a new, vital sign in dentistry.
AB  - The oral health effects of tobacco use are well documented. It is important that
      the oral health team become involved in decreasing tobacco use and preventing
      future use among their patients. By following a simple model for tobacco control
      education, such as the National Cancer Institute model, the oral health team can
      make a significant contribution toward improving the health of their patient.

PMID- 9540728
TI  - The effects of smoking on periodontal disease and periodontal therapies.
AB  - Cigarette smoking is a significant risk factor for the development of periodontal
      disease. In addition, there is an association between a reduced healing response
      subsequent to various periodontal therapies and cigarette smoking. As providers
      of dental care, it is our responsibility to inform our patients of the
      deleterious effects of smoking as well as the benefits of the cessation of this
      habit.

PMID- 9540729
TI  - Early detection is critical for oral cancer patients.

PMID- 9540730
TI  - The dental hygienist: a role model in tobacco cessation and prevention.

PMID- 9540731
TI  - A clinico-pathologic presentation. Solitary maxillary central incisor and short
      stature.

PMID- 9540732
TI  - Reflections on private care.

PMID- 9540733
TI  - The dentist's role in diagnosis and therapy. Sleep disordered breathing.

PMID- 9540734
TI  - Public professional management ownership of dental practices?

PMID- 9540735
TI  - Oral submucous fibrosis: an unusual disease.

PMID- 9540736
TI  - Clinical judgement--our most useful tool: a case of carcinoma of the tongue.

PMID- 9540737
TI  - Latex allergies: how they affect the dental profession.

PMID- 9540738
TI  - Update: New Jersey AIDS testing, reporting and confidentiality requirements.

PMID- 9540739
TI  - The dental needs of high school students in Newport News, Virginia: a pilot
      study.
AB  - To gain insight into the dental needs of high school students, the Newport News
      Health Department conducted a survey of 236 tenth graders in a city high school.
      Ages ranged from 14 to 17 with approximately half of the students black and half
      white. The average DMFT for whites (3.21) was not significantly different from
      that for blacks (3.64) (p = .332) nor was it different for gender (female 3.58,
      male 3.28; p = .498) thereby indicating a very similar caries experience for both
      race and gender. The average F/DMFT indices, however, were significantly
      different for race (p < .0001) and those for gender quite close to statistical
      significance ( p = .083). Females have the highest filling needs met (74.3%)
      followed by white males (47.8%), black females (32.5%) and black males (31.4%).
      Unmet dental needs for both whites and blacks were found to be considerably
      higher than those for the U.S. as a whole as well as for those from the
      southeast. The greater dental needs, especially among blacks and males, may
      reflect limited access to dental care or a lower perceived need for such care.
      Sealants were present in 23% of the students compared with 7% nationwide. There
      was a significant association between the presence of sealants and students
      qualifying for dental care at the Health Department through the school free lunch
      dental program (p = .036).

PMID- 9540740
TI  - A stabilized rubber dam clamp for cervical restorations: a case report.
AB  - This article presents a technique for the stabilization of rubber dam clamps with
      Triad visible light cured resin. This technique offers many advantages over the
      traditional method utilizing impression compound.

PMID- 9540741
TI  - The psychosocial implications of oral cancer.

PMID- 9540742
TI  - Survey of anesthesia practices by oral and maxillofacial surgeons in Virginia.

PMID- 9540743
TI  - Problems associated with implant maintenance.
AB  - Implants are highly successful alternatives to conventional prostheses when
      patients are properly selected and sound prosthodontic principles are followed.
      Yet problems may still be encountered during follow-up exams. The clinician must
      be educated as to possible problems and adequately prepared to manage the
      situation.

PMID- 9540745
TI  - Large mucous retention phenomenon (mucocele) of the upper lip. Case report and
      review of the literature.
AB  - An unusual presentation of a mucocele of the upper lip has been described.
      Differential diagnosis, clinical presentation, histology, and treatment were
      discussed.

PMID- 9540744
TI  - The importance of the coronal seal following root canal treatment.
AB  - Although a plethora of research on coronal microleakage does not exist, the
      studies do confirm that a sound coronal seal is of paramount importance to the
      overall success of root canal treatment. Temporary restorations provide an
      adequate seal provided they are used correctly and only for a short time. The
      best rule of thumb is as follows: a properly cleaned, shaped, and obturated tooth
      should be permanently restored as soon as possible. If the clinician suspects
      coronal microleakage has occurred over a time period of 3 months or more,
      retreatment of the root canal should be performed before placement of a permanent
      restoration. The clinical significance of coronal recontamination over a time
      period of 1 to 3 months is more ambiguous; the existing conditions of each
      individual case will determine whether retreatment is necessary. Continued
      research, especially with in vivo models, is needed in this aspect of
      endodontics.

PMID- 9540746
TI  - Intraoral lipoma: report of a case.

PMID- 9540747
TI  - The Richmond Minority Ministry in Dentistry 1850-1950.

PMID- 9540748
TI  - An alternative approach to the treatment of oral leukoplakia.

PMID- 9540749
TI  - Class II posterior composites--ways to reduce bond stress and microleakage by
      using low modulus materials.

PMID- 9540750
TI  - Needlesticks: what to do after it happens.
AB  - A needlestick injury can be a frightening and even potentially a life-threatening
      event. It needs to be treated with compassion and some urgency. The dentist
      employer should act with knowledge of the current law and with the desire to do
      whatever is best for the affected people.

PMID- 9540751
TI  - Treatment of a habitual smoker using nicotine gum: a case report.

PMID- 9540752
TI  - Celebrating 75 years of dental public health in Virginia.

PMID- 9540753
TI  - Common oral lesions in Virginians.

PMID- 9540754
TI  - The dental professional's responsibility in identifying and reporting child
      abuse.

PMID- 9540755
TI  - Informed consent and behavior management.

PMID- 9540756
TI  - Guidelines for behavior management of The American Academy of Pediatric
      Dentistry.
AB  - (1) Behavior management is only in part a science and must be recognized as an
      art form to health care delivery. (2) The goals of behavior management are to
      achieve good dental health in the child patient and to help develop the child's
      positive attitude toward dental health. (3) The objectives of behavior management
      are to establish communication and to foster education, thereby alleviating fear
      and anxiety and building a trusting relationship between dentist and child. (4)
      All decisions regarding behavior must be based on a benefit versus risk
      evaluation. (5) Parents share in the decision-making process regarding treatment
      of their children.

PMID- 9540757
TI  - The role of child protective services.

PMID- 9540758
TI  - Indirect radiation leukemogenesis in DBA/2 mice: increased expression of B2
      repeats in FDC-P1 cells transformed by intracisternal A-particle transposition.
AB  - We have previously reported that granulocyte-macrophage colony-stimulating factor
      (GM-CSF)- and interleukin-3 (IL-3)-dependent FDC-P1 cells undergo leukemic
      transformation when injected into sublethally irradiated DBA/2 mice.
      Transformation is related to aberrant activation of growth-regulatory genes by
      insertion of intracisternal A-particle (IAP) genomes. To elucidate the
      transformation process further, a subtracted cDNA library was constructed from a
      factor-independent leukemic FDC-P1 variant and the parental FDC-P1 cells.
      Screening for clones that were preferentially recognized by a total cDNA probe
      from the transformed cell line (in comparison to a similar probe from
      untransformed FDC-P1 cells) led to the isolation of 14 clones, of which six
      contained cDNA inserts encoding so-called B2 repeats, a class of short
      interspersed nucleotide elements. The expression of B2 repeats was significantly
      increased not only in the cell line from which the subtracted library was
      constructed, but also in all other leukemic FDC-P1 variants analyzed. B2 repeats
      can act as insertional mutagens and may have a role in the stabilization of
      certain oncogene and cytokine mRNAs. Interestingly, B2 repeats contain a 14
      nucleotide region that is almost completely complementary to an AU-rich sequence
      in a region of the IAP mRNA encoding the enzyme reverse transcriptase. Although
      preliminary experiments to demonstrate stabilization of IAP mRNA by hybridization
      to B2 repeat sequences remained inconclusive, it is intriguing to speculate that
      B2 repeat sequences may have a causative role in the transformation process.

PMID- 9540759
TI  - Endothelial dysfunction after bone marrow transplantation: increase of soluble
      thrombomodulin and PAI-1 in patients with multiple transplant-related
      complications.
AB  - Multiple transplant-related complications (MTRC) represent a severe condition
      after bone marrow transplantation (BMT) and are supposed to reflect systemic
      endothelial damage. Soluble thrombomodulin (sTM) and plasminogen activator
      inhibitor type-1 (PAI-1) were investigated as markers of endothelial dysfunction
      in 35 patients after autologous or allogeneic BMT and compared with the
      occurrence of the typical complications sepsis, veno-occlusive disease of the
      liver (VOD), graft-versus-host disease (GVHD), and capillary leakage syndrome
      (CLS). PAI-1 was assessed by an assay of functional activity and sTM by antigenic
      determination. In patients who had undergone allogeneic BMT and had no transplant
      related complications (TRC), PAI-1 peaked on day +14 (20 +/- 5 units/ml), and sTM
      doubled in comparison to the starting range, to 60-80 ng/ml between days +14 and
      +49. In contrast, PAI-1 and sTM were unchanged following autologous BMT. PAI-1
      was increased in sepsis, CLS, and VOD to 39-49 units/ml (p < 0.05, compared with
      patients without TRC), and in GVHD to 16-47 units/ml (not significant). Soluble
      TM increased to 63-309 ng/ml in patients with sepsis, VOD, or CLS (p < 0.05,
      compared with patients without TRC) and to 79-224 ng/ml in GVHD (not
      significant). The increase of sTM and PAI-1 was also positively correlated to the
      number of complications, so that in patients with three complications PAI-1 was
      increased 2.8-fold and sTM 3.5-fold over patients with no complications at all.
      We conclude that endothelial dysfunction is a feature of VOD, sepsis, CLS, and to
      lesser extent of GVHD and is worse in patients with multiple complications.

PMID- 9540760
TI  - Multiple myeloma in younger patients: the role of age as prognostic factor.
AB  - The presenting features of 356 previously untreated multiple myeloma (MM)
      patients grouped according to age were analyzed in order (a) to elucidate the
      possible differences in initial clinical and laboratory features between patients
      younger than 50 years and the older ones and (b) to statistically assess the
      prognostic value of the parameters considered, with particular emphasis on the
      prognostic impact of age. Patients were divided into two groups: group I included
      61 patients aged less than 50, group II comprised 295 patients aged 50 or more.
      No significant differences were found between the two groups in terms of either
      clinical or laboratory initial characteristics. The treatments adopted and the
      response to therapy did not differ in the two groups. The prognostic value of
      presenting features was evaluated for the whole cohort by univariate and
      multivariate analysis, considering both the observed survival rates and survival
      rates corrected for the effect of other independent causes of death, using a
      Poisson model. In both models, calcium level (RR 2.33), performance status (RR
      1.83), and creatinine (RR 1.69) maintained their independent negative prognostic
      value. In contrast, the impact of age was different in the two models. In fact,
      patients younger than 50 seem to have a better prognosis when the observed
      survival rates are considered, but they show an increased risk of death when the
      model takes into account the expected mortality of the underlying population. In
      conclusion, this study shows that the younger cohort of MM patients has no
      distinctive initial characteristics with respect to older patients. In
      multivariate analysis, creatinine levels, calcemia, and performance status show a
      relevant negative independent prognostic value. Regarding the prognostic impact
      of age, survival seems to be better among patients younger than 50 than in older
      patients when the observed survival rates are considered but is significantly
      worse when the mortality of the corresponding general population, is taken into
      account.

PMID- 9540761
TI  - Meropenem monotherapy versus combination therapy with ceftazidime and amikacin
      for empirical treatment of febrile neutropenic patients.
AB  - Infections remain the major cause of morbidity and mortality among neutropenic
      cancer patients. The current study addresses the question whether monotherapy
      with the new broad-spectrum carbapenem meropenem exhibits efficacy comparable to
      that of the standard combination therapy with ceftazidime and amikacin for
      empirical treatment of febrile neutropenic patients. Seventy-one patients with
      hematological malignancies (55%) or solid tumors (45%), neutropenia <
      500/microliter, and fever > 38.5 degrees C were randomly assigned to either
      meropenem (1 g every 8 h) or ceftazidime (2 g every 8 h) and amikacin (15
      mg/kg/day) intravenously. Meropenem (n = 34) and ceftazidime/amikacin (n = 37)
      were equivalent with respect to the clinical response at 72 h (62% versus 68%) (p
      > 0.05) and at the end of unmodified therapy (59% versus 62%). Gram-positive
      bacteremia responded poorly in the meropenem and ceftazidime/amikacin group (29%
      versus 25%), whereas all gram-negative bacteremias responded except for one in
      the meropenem group caused by Pseudomonas aeruginosa. All patients survived to 72
      h. One patient in each group died of gram-positive sepsis resistant to study
      medication. No significant side effects occurred in any regimen. This study
      suggests that meropenem monotherapy might be as effective as combination therapy
      with ceftazidime and amikacin for the empirical treatment of febrile neutropenic
      patients.

PMID- 9540762
TI  - Low-grade MALT lymphoma involving multiple mucosal sites and bone marrow.
AB  - Mucosa-associated lymphoid tissue (MALT) lymphomas are indolent neoplasms which
      tend to remain localized for a long time before spreading. We describe here the
      case of a 36-year-old woman with a low-grade MALT lymphoma involving the lung,
      stomach, lingual tonsil, and bone marrow at the time of diagnosis. The clonal
      origin of the pulmonary and bone marrow neoplastic infiltrates was assessed by
      means of gene rearrangement analysis. All of the involved sites were infiltrated
      by centrocyte- and monocytoid-like cells expressing the B-cell-associated
      antigens CD19 and CD20 and showed IgM lambda chain restriction; no CD5, CD10, or
      CD43 expression was detectable. As the patient had a history of recurrent
      bronchitis, and computed tomography performed 3 years before the lymphoma
      diagnosis had already revealed a lesion of the left lung, we conclude that the
      present case probably represents a pulmonary low-grade MALT lymphoma
      characterized by an early and unusual involvement of different mucosal sites and
      bone marrow.

PMID- 9540763
TI  - Treatment of prolymphocytic leukemia with cladribine.
AB  - Prolymphocytic leukemia (PLL) is a rare lymphoproliferative disorder that takes a
      rapidly progressive course and where therapeutic interventions are often
      unsuccessful. In this context, the new purine analogs may be a promising option.
      We report two cases of PLL treated with cladribine. The first patient had been
      resistant to polychemotherapy (COP) but responded well to two courses of 2-CdA.
      He achieved a partial remission, which he maintained for 15 months. The second
      patient had very advanced disease but obtained a partial response after three
      courses of 2-CdA, given as a first-line therapy in an ambulatory setting. These
      results, as well others reported in the literature, permit us to consider 2-CdA
      as a highly promising therapeutic option for PLL.

PMID- 9540764
TI  - Ticlopidine-associated aplastic anemia. A case report and review of literature.
AB  - Serious hematologic complications associated with ticlopidine have been reported,
      including aplastic anemia. We report here an additional case of fatal aplastic
      anemia due to ticlopidine. A 66-year-old male patient developed fever and
      pancytopenia 2 months after ticlopidine was started. Despite the administration
      of granulocyte colony-stimulating factor (G-CSF) and broad-spectrum antibiotics,
      as well as aggressive red cell and platelet transfusions, the patient died 16
      days after admission due to septic shock. Eighteen other cases of ticlopidine
      induced aplastic anemia published in the English literature are also reviewed and
      presented here. Eight of the total 19 patients (including the one reported here)
      have died, mostly due to infection. Of the seven who received supportive
      treatment only, four had spontaneous recovery. Nine cases were treated with G-CSF
      or granulocyte-macrophage colony-stimulating factor (GM-CSF), and response was
      observed in only four of them. Several other cases were treated with high-dose
      corticosteroids or androgens; however, it was not possible to evaluate the
      efficacy of these treatments because of the limited number of cases. In the
      absence of satisfactory treatment for ticlopidine-induced aplastic anemia at
      present, it may be reasonable to try antilymphocyte globulin or cyclosporine.
      Also, great efforts should be made in the prevention and management of infection
      accompanying this disease.

PMID- 9540766
TI  - Treatment of autoimmune neutropenia with recombinant human granulocyte colony
      stimulating factor.

PMID- 9540765
TI  - Fournier's gangrene during induction treatment of acute promyelocytic leukemia, a
      case report.
AB  - Fournier's gangrene is described as a fulminant necrotizing fasciitis of the
      scrotum and penis. Few cases have been reported in the context of acute leukemia.
      We describe a case, complicating the induction treatment of an acute
      promyelocytic leukemia with all-trans-retinoic acid and chemotherapy. The
      evolution was favorable, following surgical excision and broad-spectrum
      antibiotic therapy. The respective roles of all-trans-retinoic acid and
      granulocytopenia are discussed. This devastating and life-threatening infection
      must be kept in mind for early clinical, bacteriological, and radiological
      diagnosis and surgical management.

PMID- 9540767
TI  - A 78-year-old women with hypercalcemia now and malignancy of unknown origin 11
      years ago.

PMID- 9540768
TI  - Management of complex wounds.

PMID- 9540769
TI  - [Reconstruction of renal artery aneurysms. Vessel morphology and clinical
      results].
AB  - OBJECTIVE: To analyse retrospectively from case notes and follow-up examinations
      the effectiveness of vascular surgery for renal artery aneurysm (RAA). PATIENTS
      AND METHODS: Operations for uni- or bilateral RAA were performed, between January
      1978 and December 1996, on 61 patients (39 women, 22 men; mean age 47.4 years),
      81% with arterial hypertension. Extracorporeal reconstruction with renal
      autotransplantation was performed in 4 of the patients. Clinical examination and
      duplex sonography or angiography were performed a mean of 58.4 months
      postoperatively. RESULTS: Postoperative morbidity rate related to the surgery was
      13%; there were no early postoperative death. At the time of follow-up 80% of the
      reconstructed renal arteries were patent. 26% of hypertensive were cured of the
      hypertension, while the blood pressure was significantly reduced in 40%.
      CONCLUSIONS: Vascular reconstruction of RAA can be effective so that primary
      nephrectomy is no longer indicated. Reconstruction in situ can usually be
      successfully performed, reducing operative time and reducing surgical trauma. The
      operation is indicated in any RAA of greater than 2 cm diameter, in all patients
      with hypertension and renal artery stenosis, and also for smaller aneurysms in
      patients in good general health and in women of child-bearing age.

PMID- 9540770
TI  - [Gronblad-Strandberg syndrome from the angiological viewpoint].
AB  - HISTORY AND CLINICAL FINDINGS: A 42-year-old man was admitted for treatment of
      peripheral vascular disease in the left leg (stage III of Fontaine). A year
      before he had undergone a right aortofemoral bypass operation. On admission there
      was stenosis of the left pelvic axis and bilateral femoral artery occlusion. In
      addition there were changes in the skin with abnormal folds, loss of elasticity
      and yellowish spots over the sides of the neck and the flexor surfaces of all
      large joints. In addition vision in the left eye was impaired. These findings
      suggested connective tissue disease involving the skin, eye and arterial system.
      INVESTIGATIONS: Routine haematological tests were normal as were clotting
      parameters. Serum concentration of GOT, GPT, gamma-GT were slightly increased.
      There was a dysproteinaemia with raised HDL and LDL levels. Resting
      electrocardiogram was normal, showing sinus rhythm and left axis deviation. The
      crurobrachial pressure index was clearly abnormal: 0.6 on the right and 0.5 on
      the left. Angiography of the pelvic and left arteries revealed long-segment
      femoral and partial lower-leg occlusions bilaterally. Abdominal sonography
      indicated diffuse parenchymal calcifications in both kidneys and angioid streaks
      on bilateral fundoscopy. Skin biopsy showed defects of elastic fibres and
      perivascular inflammatory infiltration, while capillary microscopy revealed
      twisting of the capillaries, most of them with normal lumen. These findings taken
      together indicated pseudoxanthoma elasticum (PXE) or Gronblad-Strandberg
      syndrome. TREATMENT AND COURSE: A thrombendarterectomy was performed on the left
      superficial femoral artery, after which the left popliteal artery became
      palpable, the pressure indices for the left leg were slightly better, and the
      patient was discharged home without further complications and improved leg
      perfusion. CONCLUSION: Possible cardiovascular involvement had to be taken into
      account in patients with PXE, and long-term angiological monitoring is indicated.

PMID- 9540771
TI  - ["Purple glove syndrome." Severe soft tissue reaction following phenytoin
      infusion].
AB  - HISTORY AND ADMISSION FINDINGS: A 37-year-old woman, known since childhood to
      suffer from generalized seizures, was sent to the intensive care unit in status
      epilepticus. On admission tonic-clonic seizures persisted even after
      intravenously administration of clonazepam, 2 x 1 mg. She was unconscious and
      reacted unfocused to painful stimuli. TREATMENT AND COURSE: Further seizures
      occurred with vomiting and respiratory failure threatened. After intubation
      phenytoin was given intravenously (initially 250 mg over 10 min, then 750 mg over
      24 h) into a vein on the dorsum of the hand. The seizures stopped. Within a few
      hours a livid swelling developed at the site of the needle puncture on the right
      hand, which spread to the lower arm (purple glove syndrome) and the patients
      could no longer move her arm because of pain. The condition improved with anti
      inflammatory treatment and antibiotics as well as local measures. On discharge
      she was able to make a first without pain. However, she was re-admitted 3 weeks
      later because of renewed painful impairment of right hand movement and the
      picture of early Sudeck's atrophy. Under regional anaesthesia complete mobility
      and freedom from pain was achieved within 2 weeks. CONCLUSION: Administration of
      phenytoin into a peripheral vein, especially of the hand, can cause soft tissue
      damage and should be avoided. Primarily the oral route is to be preferred.

PMID- 9540772
TI  - [State-of-the-art therapy for primary sclerosing cholangitis].

PMID- 9540773
TI  - [Rehabilitation and exercise training for older patients with heart
      insufficiency].

PMID- 9540774
TI  - [Rehabilitation of the chronically ill and handicapped. Survey and perspectives].

PMID- 9540775
TI  - [Continuation of contract practice during motherhood].

PMID- 9540776
TI  - [Diagnosis of sprue/celiac disease].

PMID- 9540777
TI  - Exon scrambling of MLL transcripts occur commonly and mimic partial genomic
      duplication of the gene.
AB  - The MLL gene is frequently rearranged in acute human leukemia of both the myeloid
      and lymphoid lineages. Using a sensitive reverse transcriptase-polymerase chain
      reaction (RT-PCR) assay, we identified several abnormally spliced transcripts in
      which MLL exons were joined in an order different from the genomic orientation
      (scrambled exons). Mis-splicing of MLL was present in both normal and malignant
      tissues. Although the majority of these scrambled transcripts were joined
      accurately at consensus splice sites, there were several examples in which the
      junctions of exons spliced in aberrant order were at non-consensus sites. A
      number of features differentiate mis-splicing of MLL from the previously
      described cases of scrambled exons and circular RNAs. Some scrambled transcripts
      appear to be present in the polyadenylated fraction of RNA. No correlation of
      exon scrambling with exon skipping was found, and there was no particular
      tendency for the exons involved to be near large introns. Our data show that
      splicing of MLL is extremely complex. The presence of scrambled transcripts in
      both normal and leukemic cells, indistinguishable from transcripts resulting from
      genomic MLL rearrangements, precludes the use of nested RT-PCR as a screening
      method for detection of tandem duplication of tandem duplication of MLL.

PMID- 9540778
TI  - [Morphological and functional aspects of the cardiovascular system related to
      aging: does "aging heart" exist?].
AB  - Elderly people are the most rapid growing segment of society, and heart disease
      is the most common cause of death in this population. The aging process is
      associated with anatomic and physiologic alterations in the cardiovascular
      system; consequently, the manifestations of disease in the geriatric population
      differ from those involving younger patients. To formulate diagnosis of "aging
      heart" in older patient may be difficult, because of atypical symptoms or of the
      acceptance of symptoms as manifestations of old age. Aging is, moreover, often
      associated with a decline in physical activity, which may result in
      cardiovascular "deconditioning". The treatment strategy is the same as in younger
      patients, but the higher incidence of adverse effects and complications demands
      special awareness. In this article we discuss about age-related structural and
      functional changes that occur in the cardiovascular system, including changes in
      the heart muscle, valves, conduction system and major arteries.

PMID- 9540779
TI  - Hypercoagulability and chronic atrial fibrillation: the role of markers of
      thrombin generation.
AB  - BACKGROUND: We have studied 64 patients with congestive heart failure, half of
      them also with chronic nonvalvular atrial fibrillation (AF). Patients were also
      stratified according to a history of prior stroke. METHODS: The generation of
      thrombin was investigated by means of the molecular markers prothrombin fragment
      1 + 2 (F1 + 2) and thrombin-antithrombin III complex (TAT), because AF patients
      may have a hypercoagulable state. There was only a trend toward higher values of
      TAT and F1 + 2 for AF patients, while subjects with previous stroke (irrespective
      of AF) had increased levels of the markers of thrombin generation (TAT stroke+
      18.95 +/- 5.15 vs TAT stroke- 8.34 +/- 2.41; F1 + 2 stroke+ 2.22 +/- 0.29 vs F1 +
      2 stroke- 1.32 +/- 0.12). The presence of spontaneous echo contrast (SEC) within
      left atrium was also investigated in 32 AF patients by transesophageal
      echocardiography. RESULTS: TAT were significantly higher in subjects (n = 11)
      with SEC (TAT sec+ 37.5 +/- 13.41 vs TAT sec- 8.7 +/- 2.51, p = 0.008).
      CONCLUSIONS: Finally, when we grouped into 1) those with both AF and stroke, 2)
      AF alone, 3) stroke alone and 4) sinus rhythm without stroke, levels of F1 + 2
      were higher (and marginally higher TAT) in patients with AF and stroke than in
      those without stroke, revealing that there is a true clotting activation state in
      these subjects.

PMID- 9540780
TI  - [Prevention of the extension of distal deep venous thrombosis. A randomized
      controlled trial with a 6-month follow-up].
AB  - BACKGROUND: Deep venous thrombosis (DVT) of distal veins of the legs is important
      for its frequency and its potential proximal extension. The incidence of
      embolization in distal DVT is limited and treatment still undefined. METHODS:
      After diagnosing with duplex scanning a distal DVT patients were included in a 24
      week follow-up. All subjects used elastic compression (stockings TED =
      thromboembolic deterrent) for 24 weeks after DVT. In the 4 groups the following
      prophylaxis for 8 weeks were used: A: oral anticoagulant (INR 2.5). B:
      subcutaneous calcium heparin 0.2 ml bid (8.00 and 20.00). C: subcutaneous calcium
      heparin (0.5 ml at 20.00). D was the control group (only elastic TED stockings).
      heparin 0.2 ml bid (5000 IU) and 0.5 ml once daily (12.500 IU) were used for
      individuals with weight range between 65 and 90 kg. No patient was admitted into
      hospitals. Initially 106 patients were included. There were 17 (9.6%) drop outs
      and after 8 weeks 177 patients completed the study. No pulmonary embolisation or
      side effects were observed. In one patient (control group) an important extension
      of the thrombus to the femoral and iliac veins was observed. RESULTS: The
      percentage of thrombus reduction was higher in the treatment groups than in
      controls (p < 0.05). No significant differences were found among the 3 treatment
      groups. At 8 weeks 88.6% of patients treated with oral anticoagulant showed
      improvement (stability/reduction in size of the thrombus; the percentage was
      88.4% in subjects treated with subcutaneous heparin bid and 93.2% in those
      treated with a single dosage). In the control group thrombus increase was
      observed in 78.3% of patients (this difference was significant in comparison with
      the treatment groups; p < 0.05). At the 24-week control in 97.6% of patients in
      group A thrombosis was reduced/stable. This percentage was 97.7% in the ca
      heparin double-dose group (B) and 100% in the single dose group (C),
      significantly lower than in group D (75%; p < 0.05). CONCLUSIONS: Results
      indicate that untreated subjects with distal DVT are at risk of thrombus
      extension. In this study treatments were clinically equivalent. However one
      single dose of subcutaneous heparin is as effective as the double dose, is better
      tolerated, does not require haematological monitoring and has a lower cost.

PMID- 9540781
TI  - Fibers in the Mediterranean diet. An epidemiological study of the Campania
      Region.
AB  - BACKGROUND: The authors have evaluated: a) the survival of the "mediterranean
      diet" as way of life; b) the comparison between fiber content in the diet of
      adult or school children of the Campania Region. METHODS: To study nutritional
      epidemiology of adults, a new method consisting of publishing a 24-hour recall
      dietary chart in a new paper with big regional circulation, Il Mattino, and
      analyzing all the charts from the different towns of Campania was used. For that,
      the ZIP code of the subject was used as an informatics button. Data were housed
      in a computer using Food Meter (an informatics program by Bayer-Medimatica).
      RESULTS: Differences statistically significant were found between adults or
      children residing in various district of the Campania Region and Naples town.
      CONCLUSIONS: Finally, it is important to underline that the amount of fibers of
      children's diets was higher than adult diets.

PMID- 9540782
TI  - [Pulmonary embolism of paraneoplastic origin].
AB  - Thromboembolic disease (TE) is an important cause of in-hospital morbidity and
      mortality. The relationship between cancer and abnormalities of blood coagulation
      has been recognized for well over a century. Deep venous thrombosis (DVT) of the
      lower extremities is the most common cause of thromboembolic disease, but
      pulmonary embolism, upper extremity vein thrombosis, disseminated intravascular
      coagulation, and other, more unusual, clinical events, may occur. Unexplained TE
      may serve as a marker for the presence of a hidden tumor. The frequency of
      pulmonary embolism (PE) among patients with a malignant neoplasm at necropsy is
      highly increased in the elderly patients. Among subjects with a malignant
      neoplasm, patients with pancreatic and gastric cancer (mucin-secreting
      adenocarcinomas), cancer of the large bowel and women with ovarian cancer had the
      highest frequency of PE. Old age, female sex, gastrointestinal and ovarian
      cancers must be considered as a significant risk factor for PE. The potentially
      responsible mechanisms for the thrombotic events, clinical manifestations,
      diagnostic implications and aspects of treatment of TE in malignant disease are
      discussed.

PMID- 9540783
TI  - [Aplastic anemia in acute viral hepatitis type A. Our experience].
AB  - A case of posthepatitis A aplastic anemia is described. The pathogenesis of this
      rare complication of viral hepatitis type A infection is underlined.

PMID- 9540784
TI  - [Tropical pyomyositis. A case report].
AB  - Tropical pyomyositis is an infection of large muscle groups that can lead to
      sepsis and death. The most common etiologic agent is Staphylococcus aureus. It
      usually occurs in patients living in the tropics but is seen with increasing
      frequency in temperate climates, particularly in immunosuppressed patients, where
      it may be misdiagnosed and may cause severe morbidity and mortality. Diagnosis is
      based on the examination of pus from a muscle aspirate and treatment consists of
      surgical incision, drainage and appropriate antibiotic therapy. It is stressed to
      take into account pyomyositis in the differential diagnosis of immunocompromised
      patients with "cryptic" myalgia.

PMID- 9540785
TI  - [Use of mesoglycan in venous pathology].
AB  - Twenty-five female patients suffering from primary venous insufficiency of the
      lower limbs underwent parenteral and oral treatment with mesoglycan for 3 months.
      In addition to an evaluation of the subjective and objective parameters linked to
      venous insufficiency, all patients underwent lower limb venous echo colour
      Doppler and videocapillaroscopy using an optic probe in a perimalleolar or
      periulcerous site. At the end of treatment, all patients reported an improvement
      in subjective parameters, which was confirmed by a reduction of distal edema in
      22 out of 25 cases. There was also an improvement in capillaroscopic findings
      (reduction of edema of pericapillary connective tissue, reduction of capillary
      and venular ectasia.

PMID- 9540786
TI  - [Problems associated with the use and monitoring of cyclosporin. Experience at a
      Clinical Pharmacology Service].
AB  - BACKGROUND: A study on cyclosporine A (CyA) monitoring in the January 1992
      December 1995 period is reported. The aim of this work was to give
      epidemiological data on the use of CyA, to verify the progressive increase of CyA
      determinations and to evaluate the use in other diseases as well as to compare
      the different technics of CyA assay in blood samples, to stress the timing of
      blood samples and to underline the CyA monitoring importance. METHODS: The CyA
      dosage was evaluated by fluorescence polarization immunoassay (FPIA) and high
      performance liquid chromatography (HPLC). RESULTS: The study showed that 70% of
      CyA determinations come from patients undergone to renal, bone marrow and liver
      transplantations; the remaining 30% was associated to other diseases (psoriasis,
      uveitis, diabetes, rheumatoid arthritis). CONCLUSIONS: The results obtained
      showed a progressive and constant increase of CyA determinations. Moreover, the
      use of drug was increased in autoimmune diseases. It is stressed that CyA
      monitoring in blood samples is essential to optimize the therapeutic efficacy of
      drug and minimizing its toxicity.

PMID- 9540787
TI  - Function and conformation of wild-type p53 protein are influenced by mutations in
      bovine leukemia virus-induced B-cell lymphosarcoma.
AB  - The mutations of the p53 gene previously represented one of several genetic
      changes involved in the development of bovine leukemia virus (BLV)-induced
      lymphosarcoma, while the effects of these mutations on the function of p53 are
      unknown. We identified four mutations of p53 gene in BLV-infected cattle with
      lymphosarcoma and demonstrated clearly the existence of two functionally distinct
      groups of mutants: (i) the mutant forms with substitutions at codons 241 and 242,
      which were mapped within an evolutionally conserved region and corresponded to
      the human "hot-spot" mutations, had completely lost the capacities for
      transactivation and growth suppression and gained transdominant repression
      activity in p53-null SAOS-2 cells; and (ii) the mutations at codons 206 and 207
      were located outside the evolutionally conserved regions. These mutants partially
      retained the capacity for transactivation and growth suppression and failed to
      inhibit the transactivation activity of coexpressed wild-type p53, instead
      showing an enhancement of this activity. In addition, protein analysis using an
      antibody specific for the mutant form revealed that the mutations at codons 206
      and 242 induced a "mutant" conformation of the bovine p53 proteins. Collectively,
      these results show that mutations of p53 gene in BLV-infected cattle with
      lymphosarcoma can potentially alter its physiological function and may play an
      important role in BLV-induced leukemogenesis.

PMID- 9540788
TI  - Cloning and sequencing of cDNA encoding the LS-12 antifreeze protein in the
      longhorn sculpin, Myoxocephalus octodecimspinosis.
AB  - cDNA coding for an antifreeze protein (LS-12) in the longhorn sculpin,
      Myoxocephalus octodecimspinosis, was prepared from liver mRNA using reverse
      transcriptase-polymerase chain reaction coupled with 3' and 5' RACE procedures.
      This cDNA contains 609 base pairs, including a 384-bp open reading frame which
      codes for a 128-residue LS-12 precursor protein. The predicted amino acid
      sequence of the mature LS-12 corresponds exactly to the amino acid sequence
      obtained from Edman degradation [G. Deng, D.W. Andrews, R.A. Laursen, FEBS Lett.,
      402, 1997, pp. 17-20]. The 20 residues preceding mature LS-12 are predicted to be
      a signal sequence, which is presumably cleaved off before the mature, 108-residue
      protein is secreted into the circulatory system. This is the first report of a
      cDNA sequence from M. octodecimspinosis.

PMID- 9540789
TI  - Purification and molecular cloning of a chitinase expressed in the hepatopancreas
      of the penaeid prawn Penaeus japonicus.
AB  - A protein with chitinase activity was purified from the hepatopancreas of the
      penaeid prawn Penaeus japonicus, and the amino acid sequences of several amino
      acid fragments were determined. A cDNA clone was isolated and sequenced which
      contained the coding sequence of the enzyme. The conceptually translated protein
      (named Pjchi-3) was a member of the chitinase family based on sequence
      similarities to chitinases of non-crustacean species, as was the case with Pjchi
      1 and 2, two chitinase homologues previously isolated from P. japonicus.

PMID- 9540790
TI  - Thermostable glycerol kinase from Thermus flavus: cloning, sequencing, and
      expression of the enzyme gene.
AB  - The thermostable glycerol kinase (EC 2.7.1.30) gene from Thermus flavus was
      cloned and expressed in Escherichia coli DH5 alpha. An open reading frame of 1488
      bp for the glycerol kinase gene (glpK) starting with an ATG methionine codon was
      found, which encodes a protein of 496 amino acid residues whose calculated
      molecular weight is 54,835. The amino acid sequence of T. flavus glycerol kinase
      is 80.6% and 64.1% identical with those of Bacillus subtilis and E. coli.
      Transformants of E. coli DH5 alpha harboring plasmid pGYK12 with a 1505 bp
      chromosomal DNA fragment containing the T. flavus glycerol kinase gene showed
      about 23.8-fold higher glycerol kinase activity than T. flavus.

PMID- 9540791
TI  - The structural aspects of limited proteolysis of native proteins.

PMID- 9540792
TI  - A novel thermostable neutral proteinase from Saccharomonospora canescens.
AB  - A novel thermostable neutral proteinase, called NPS, was purified to
      electrophoretic homogeneity from the culture broth of Saccharomonospora canescens
      sp. novus, strain 5. The molecular mass was determined by SDS-polyacrylamide gel
      electrophoresis to be 35,000 Da. The enzyme exhibits a sharp pH optimum of
      proteolytic activity at pH 6.7. NPS was completely inactivated with inhibitors,
      typical for metalloendopeptidases, EDTA and 1,10-phenantroline, whereas the
      serine proteinase inhibitor PMSF had no effect. Atomic absorption measurements
      showed that the proteinase binds a single zinc and four calcium ions. The enzyme
      thermostability was characterized in the absence and presence of added calcium.
      Melting temperature, Tm = 77 degrees C and an activation energy, Ea, for the
      thermal deactivation of the excited protein fluorophores of 72.13 kJ mol-1 were
      calculated in the presence of 100 mM CaCl2. The Ea-value is considerably higher
      than those obtained for a number of proteinases from microorganisms and was
      explained by the thermostable structure of the enzyme. Effective radiationless
      energy transfer from phenol groups to indole rings was observed. 68% of the light
      absorbed by tyrosyl residues is transferred to tryptophyl side chains. No
      homology was found after comparison of the NPS N-terminal sequence, including the
      first 26 residues, with those of other neutral proteinases from microorganisms.
      In contrast to the well-known bacterial neutral proteinase thermolysin and
      related enzymes from microorganisms, NPS possesses arylamidase and esterase
      activities. Further crystallographic studies will reveal the structural reasons
      for this specificity. Epoxy and epithio pyranosides are inhibitors of the
      proteinase arylamidase activity.

PMID- 9540793
TI  - Oligomeric structure of hepatic lipase: evidence from a novel epitope tag
      technique.
AB  - The subunit structure of purified rHL (rHL) was determined by gel filtration
      chromatography, density gradient ultracentrifugation studies and a novel approach
      using epitope-tagged rHL. By gel filtration studies, native rHL had an apparent
      molecular weight of 179 kDa whereas enzyme treated with 6 M guanidine
      hydrochloride (GuHCl) for 22 h at room temperature gave a protein peak at 76 kDa.
      Using milder conditions for denaturation of rHL, such as 1 M GuHCl for 2 h, rHL
      eluted in two distinct peaks, one at 179 kDa and the other at 76 kDa. In
      addition, both protein peaks produced under mild denaturing conditions possessed
      detectable catalytic activity. Consistent with studies on lipoprotein lipase, the
      denatured rHL eluted from heparin-Sepharose at a lower salt concentration of 0.42
      M NaCl than the native rHL which eluted at 0.72 M NaCl. By density gradient
      ultracentrifugation studies, the estimated molecular weight of native rHL was
      determined to be 113 kDa. Together, the data suggest that native rHL exists as a
      dimer that can be denatured into monomers by GuHCl and that a fraction of the
      denatured enzyme has detectable enzyme activity. To confirm these results, we
      designed two different rHL constructs that were epitope-tagged with either the
      myc or flag epitope and transfected them into 293 cells. The addition of the tag
      was shown not to alter enzyme secretion rate or specific activity of the lipase.
      Partially purified lipase from media of cotransfected cells was used to establish
      a dimer assay which employed a sandwich ELISA. This assay firmly established the
      presence of a rHL species which contained both the myc and flag tags, supporting
      an oligomeric subunit structure for rHL. Furthermore, the data using the epitope
      tagged enzyme shows that this method could be a useful tool not only in
      identifying the region of the lipase responsible for dimer formation but also to
      study other protein-protein interactions.

PMID- 9540795
TI  - Characterization of the monovalent and divalent cation requirements for the
      xenobiotic carboxylic acid: CoA ligases of bovine liver mitochondria.
AB  - The XL-I, XL-II and XL-III forms of xenobiotic/medium-chain fatty acid: CoA
      ligase were found to be inactive toward benzoate in the absence of either
      monovalent or divalent cations. The absolute requirement for monovalent cation
      was satisfied by either K+, Rb+, or NH4+. Na+ only supported a very low rate.
      Varying the nature of the anion had only a minor effect. For XL-I and XI-II, the
      optimum concentration of K+ was 50 mM; higher (physiologic) concentrations led to
      a decrease in activity. K+ did not inhibit XL-III. The absolute requirement for
      divalent cation was satisfied by Mg2+ or Mn2+, or to a lesser extent by Co2+ or
      Fe2+. For the XL-I and XL-II, excess uncomplexed Mg2+ or Mn2+ decreased the rate;
      the optimum concentration of Mn2+ was approximately the same as the concentration
      of ATP in the assay, and the optimum concentration of Mg2+ was approximately
      double the concentration of ATP in the assay. This is consistent with the concept
      that the divalent cation is required to complex with ATP and with the known
      stability constants for the ATP complexes of these two divalent cations. XL-III
      was not inhibited by uncomplexed divalent cations. Uncomplexed ATP was a moderate
      inhibitor of XL-I and XL-II, and a weak inhibitor of XL-III. The data indicate
      that in vivo benzoate conjugation is K+ and Mg2+ dependent, and that the cation
      effects are complex and differ for XL-I and XL-II as compared with XL-III.

PMID- 9540794
TI  - Identification and characterization of receptors for riboflavin carrier protein
      in the chicken oocyte. Role of the phosphopeptide in mediating receptor
      interaction.
AB  - Riboflavin carrier protein (RCP) is a phosphoglycoprotein found in the egg and
      the serum of laying birds and other animals. We have investigated the binding of
      chicken RCP (cRCP) to membranes prepared from the whole chicken oocytes. RCP
      binding had an absolute requirement for calcium, with an affinity (Kd 10(-8) M)
      high enough to be physiologically relevant. Ligand blotting experiments using
      labeled RCP and vitellogenin, with proteins solubilized from oocyte membranes,
      indicated that RCP and vitellogenin bound specifically to three proteins of Mr
      380, 260 and 110 kDa. Vitellogenin also bound to proteins of Mr 515 kDa and 97
      kDa, similar in size to those identified by receptor associated protein of RAP.
      Reduced and carboxyamidated RCP inhibited the binding of 125I-labeled RCP to
      chicken oocyte membranes, but recombinant RCP expressed in E. coli, and
      dephosphorylated RCP, failed to interact with the receptors, indicating that post
      translational modifications were necessary for ligand-receptor interaction. The
      purified phosphopeptide, prepared from tryptic digests of egg white RCP, was able
      to inhibit the binding of RCP to the receptor proteins, with an affinity
      comparable to native RCP indicating that the phosphopeptide sequence present in
      RCP serves as the focal point for RCP-receptor interactions.

PMID- 9540796
TI  - The monolayer technique as a tool to study the energetics of protein-protein
      interactions.
AB  - In this paper, we explore the possibility of using the monolayer technique and
      hydrophobic homopolypeptides to study the energetics of protein stability. We
      have studied the stabilization of the bilayer state of poly-L-alanine in its
      alpha-helical conformation at the air-water interface by measuring compression
      and expansion surface pressure (II)-residual area (A) isotherms at 22 +/- 2
      degrees C. The Gibbs free energy of stabilization per alanyl residue transferred
      from the water exposed state in the monolayer to the inside of the bilayer was
      calculated from the surface area of the hysteresis loops obtained during
      compression-expansion cycles performed during the monolayer to bilayer
      transition. Using atomic solvation parameters and the water accessible surface
      area per atom group for an alanyl residue in a standard alpha-helix, we have
      dissected the free energy of stabilization per alanyl residue into the change of
      solvation free energy (delta Gs) upon transfer from the water surface to the
      inside of the bilayer state, and the free energy associated to the formation of
      hydrophobic van der Waals interactions (delta GvdW) in the bilayer. We estimate a
      value of 25 +/- 4 cal/(mol A2) for the hydrophobic interaction, as defined by the
      sum of delta Gs and delta GvdW per unit of hydrophobic (aliphatic) accessible
      surface area in an alanyl residue.

PMID- 9540797
TI  - Measurement of peptide aggregation with pulsed-field gradient nuclear magnetic
      resonance spectroscopy.
AB  - Interactions between hydrophobic patches in proteins are often a driving force
      for denaturation and aggregation. The aggregation of the beta-amyloid peptide
      fragment, VHHQKLVFFAEDVGSNK (beta(12-28)), has been investigated in aqueous
      solution at low pH. This peptide contains a central hydrophobic patch spanning
      residues 17-21. Diffusion coefficients measured with pulsed-field gradient NMR as
      a function of peptide solution concentration were used to assess the extent of
      aggregation. Following the hypothesis that hydrophobic interactions are an
      important driving force in the aggregation of this peptide at low pH, a non
      aggregating analog of the beta(12-28) peptide, [Gly19,20]beta(12-28) was
      synthesized. In the [Gly19,20]beta(12-28) peptide, the replacement of the two
      phenylalanine residues disrupts the hydrophobic interactions which drive the
      aggregation of beta(12-28). The diffusion coefficient of the [Gly19,20]beta(12
      28) peptide is invariant over the concentration range studied and provides a good
      estimate of the monomeric diffusion coefficient of beta(12-28). A second peptide
      analog was synthesized in which the phenylalanine at position 20 was replaced
      with a cysteine residue. The disulfide-linked dimer, ([Cys20]beta(12-28))2, was
      formed upon air oxidation of this peptide. The diffusion coefficient of the
      ([Cys20]beta(12-28))2 peptide was measured and used to estimate the diffusion
      coefficient of the beta(12-28) dimer. Using the monomeric and dimeric diffusion
      coefficients measured for the glycine and cysteine analogs, the concentration
      dependence of the beta(12-28) diffusion coefficient was found to be consistent
      with a monomer-dimer aggregation model.

PMID- 9540798
TI  - Interactions of serine proteinases with pNiXa, a serpin of Xenopus oocytes and
      embryos.
AB  - In a previous study, kinetic assays showed that pNiXa, an Ni(II)-binding serpin
      of Xenopus oocytes and embryos, strongly inhibits bovine chymotrypsin, weakly
      inhibits porcine elastase, and does not inhibit bovine trypsin. In this study,
      analyses by SDS-PAGE and gelatin zymography showed that an SDS-resistant complex
      is formed upon the interaction of pNiXa with bovine chymotrypsin. No such pNiXa
      enzyme complex was detected after pNiXa interactions with porcine elastase,
      bovine trypsin, or human cathepsin G. The major products of pNiXa cleavage by the
      four proteinases were partially sequenced by Edman degradation. The cleavage
      products were also tested by immunoblotting with an antibody to the His-cluster
      of pNiXa, and by radio-blotting with 63Ni(II). These assays showed that
      chymotrypsin and elastase cleave pNiXa at the P1-P1 (Thr-Lys) peptide bond near
      the C-terminus, while trypsin and cathepsin G cleave pNiXa at specific peptide
      bonds near the N-terminus, within an interesting 26-residue segment, rich in Lys
      and Gln, that separates the His-cluster of pNiXa from the rest of the molecule.
      The segment lacks homology to other serpins, but resembles a domain of Xenopus
      POU3 transcription factor. This study identifies the specific sites for
      interactions of four serine proteinases with pNiXa, indicates that pNiXa
      inhibition of chymotrypsin involves a serpin-like mechanism, and shows that
      63Ni(II)-binds to the His-cluster of pNiXa.

PMID- 9540799
TI  - Crystal structures of 5-fluoro-dUrd and its 2 and/or 4-thio analogues: models of
      substituted dUMP pyrimidine ring interacting with thymidylate synthase.
AB  - In order to understand the influence on thymidylate synthase interactions with
      dUMP analogues of the pyrimidine ring 2- and/or 4-thio, and 5-fluoro
      substitutions, X-ray diffractions by crystals of 5-fluoro-dUrd and its 2- and 4
      thio, and 2,4-dithio analogues were measured, the four structures solved and
      refined. The following conclusions were suggested by results of comparative
      analyses of structural parameters (bond lengths, valence angles), followed by
      theoretical considerations based on calculated resonance structure distributions
      and aromaticity indices of the uracil, thiouracil, fluorouracil and
      fluorothiouracil rings. The effect of 4-thio substitution of FdUMP, altering
      specificity of inactivation of thymidylate synthases from various sources, is
      probably due to weaker proton acceptor power of the 4-thio substituent and
      increasing acidity (enhanced proton-donor power) of the N(3)-H moiety, resulting
      in an impaired fitness into the network of hydrogen bonds in the enzyme active
      center cleft. 2,4-Dithio substitution results in (i) impaired pyrimidine ring
      recognition by the enzyme active center, due to the 4-thio substituent (ii)
      increased pyrimidine ring aromaticity in dUMP, leading to resistance of C(6) to
      nucleophilic attack by the enzyme active center cysteine and (iii) altered
      planarity of the pyrimidine ring and deflections, with respect to the ring plane,
      of substituents at C(2), C(4) and C(5). 5-Fluoro substitution apparently
      activates the pyrimidine ring towards the interaction with thymidylate synthase
      by producing local strain, which results in an increased reactivity as predicted
      by the Walsh-Bent rule.

PMID- 9540800
TI  - Identification of CYP2E1 in marmoset monkey.
AB  - CYP2E1 is the main enzyme responsible for chlorzoxazone 6-hydroxylase activity in
      human liver. Here, it is shown that marmoset monkey liver microsomal fraction
      catalyses this reaction at a similar rate and with a similar Km to human liver
      and that the activity is increased 4-fold in marmosets treated with isoniazid, a
      known inducer of CYP2E1. This indicates that CYP2E1 is present in marmoset liver.
      However conversely, an anti-peptide antibody targeted against the C-terminus of
      human and cynomolgus monkey CYP2E1 (Val-Ile-Pro-Arg-Ser) failed to bind to
      marmoset monkey hepatic microsomal fraction. To investigate if there is a
      difference in the C-terminus of CYP2E1 in these species, this region of marmoset
      CYP2E1 was sequenced following amplification of marmoset liver cDNA with primers
      selected according to conserved regions identified in human and cynomolgus monkey
      CYP2E1. It was found that the deduced amino acid sequence of marmoset CYP2E1 in
      this region is very similar to human CYP2E1, but due to two base differences in
      the marmoset nucleic acid sequence, the C-terminus of marmoset CYP2E1 is extended
      by 2 amino acids, i.e. Val-Ile-Pro-Arg-Ser-Ser-Val. This difference is sufficient
      to prevent the binding of an antibody raised against the C-terminus of human
      CYP2E1. The expression of CYP2E1 in the marmoset was confirmed by raising an
      antibody against the deduced C-terminus of marmoset CYP2E1 (Pro-Arg-Ser-Ser-Val).
      In immunoblotting, this antibody bound to a single protein of 54 kDa in marmoset
      liver microsomal fraction. The intensity of the band was increased in isoniazid
      treated marmosets, consistent with induction of CYP2E1. The antibody did not
      recognise human or cynomolgus monkey CYP2E1. This was expected since the
      immunising peptide sequence does not occur in these enzymes. The results
      demonstrate the presence of CYP2E1 in marmoset liver and illustrate the
      importance of the C-terminus for the production of specific antibodies against
      P450 enzymes.

PMID- 9540801
TI  - Structure/function analysis of the domains required for the multimerisation of
      phenylalanine hydroxylase.
AB  - Phenylalanine hydroxylase (PAH) exists as an equilibrium of dimers and tetramers.
      However, there is little information concerning the inter- or intra-molecular
      interactions required for enzyme quaternary structure. It is predicted that the
      formation of a PAH tetramer will require at least two points of contact per
      enzyme subunit. Sequence analysis has suggested the existence of a C-terminal
      domain with characteristics of a leucine zipper or a variant of this called a
      coiled-coil. By deletion of 24 amino acids from the C-terminus or conversion of
      leucine 448 to an alanine residue, we have shown that this putative leucine
      zipper/coiled-coil domain is involved in the assembly of an active enzyme
      tetramer from dimers. The removal of this C-terminal domain of PAH reduces enzyme
      activity but does not abolish it. Furthermore, we report that an alanine 447 to
      aspartate mutation associated with phenylketonuria may affect subunit assembly
      which suggests the formation of enzyme tetramers is physiologically relevant. Our
      analysis of subunit interactions in vivo, show that in the absence of the C
      terminal coiled-coil domain, dimers can form and this is only possible when the N
      terminal domain is present. This provides the first evidence that N-terminal
      domain is required for multimerisation. We propose that the N-terminal regulatory
      domain in conjunction with the C-terminal coiled-coil domain, mediates the
      formation of fully active enzyme tetramers.

PMID- 9540802
TI  - Albumin Church Bay: 560 Lys-->Glu a new mutation detected by electrospray
      ionisation mass spectrometry.
AB  - Albumin Church Bay is a fast migrating genetic variant of human serum albumin
      which, in a heterozygous subject, formed about 50% of the circulating albumin.
      Reversed phase peptide mapping and electrospray ionisation mass spectrometry (ESI
      MS) indicated that the C-terminal CNBr peptide had decreased polarity associated
      with a 1 Da increase in mass. Subdigestion of this peptide with trypsin and
      chymotrypsin revealed that the increased mass was associated with the
      chymotrypsin fragment VEKCCKADDKETCF (555-568) which had a mass of 1791.1
      compared to 1790.2 for its normal counterpart. Sequence analysis of PCR-amplified
      DNA indicated an A-->G mutation at position 98 of exon 13, which causes a point
      mutation of 560 Lys-->Glu and results in a 1 Da mass increase.

PMID- 9540804
TI  - A stable, molten-globule-like cytochrome c.
AB  - Expression of cytochrome c from Thermus thermophilus in Escherichia coli (E.
      coli) leads to a protein with characteristics of a molten globule. Unfolding
      induced by guanidine hydrochloride (GdHCl) shows that E. coli-expressed
      cytochrome c has lower stability (and less cooperativity of unfolding) compared
      to the protein extracted from Thermus thermophilus, even though the two proteins
      have identical amino-acid sequences. Moreover, Soret and far-UV circular
      dichroism signals differ for the two proteins, suggesting a distorted heme
      environment and more side-chain dynamics of E. coli-expressed cytochrome c.
      Still, tryptophan fluorescence in E. coli-expressed cytochrome c is quenched as
      in native protein, and the iron coordinates in a low-spin form. Amino-acid
      sequencing indicates the presence of only one covalent cysteine-linkage to the
      heme in E. coli-expressed cytochrome c (normally, there are two linkages), a
      possible explanation for the trapped, molten-globule-like structure. The features
      of this non-native protein may be of interest for interpretation of cytochrome c
      folding kinetics in vitro, since a molten globule may be an intermediate on the
      folding pathway.

PMID- 9540803
TI  - Novel lectin-related proteins are major components in lima bean (Phaseolus
      lunatus L.) seeds.
AB  - The only component of the lectin-related protein family so far reported in Lima
      bean (Phaseolus lunatus L.) seeds is the minor seed lectin (LBL). In the
      morphotype Big Lima, we have isolated and characterised two abundant lectin
      related seed proteins and the corresponding cDNA clones. The clones show 93.7%
      nucleotide identity and encode an arcelin-like (ARL) and an alpha-amylase
      inhibitor-like (AIL) protein. Not considering the signal peptides, ARL and AIL
      polypeptides contain 239 and 233 amino acids, respectively. Each polypeptide is
      present in the mature protein as two glycoforms. ARL subunits (43 and 46 kDa)
      make up oligomers of about 125 to 130 kDa whereas AIL subunits (40 and 42 kDa)
      oligomerise in dimers of about 88 to 100 kDa. cDNA clones encoding two isoforms
      of the less abundant Lima bean lectin were also isolated. In common bean (P.
      vulgaris) the lectin locus encodes the lectin and the lectin-related proteins
      alpha-amylase inhibitor and arcelin, all plant defence proteins. Our data
      indicate extensive evolution of the locus also in Lima bean.

PMID- 9540805
TI  - Studies on the urea cycle enzyme ornithine transcarbamylase using heavy atom
      isotope effects.
AB  - Ornithine transcarbamylase (OTCase) catalyzes the reaction between L-ornithine
      and carbamyl phosphate in the first step of the urea cycle. 13C isotope effects
      were measured in carbamyl phosphate, using OTCase obtained from E. coli in a one
      column purification which yielded 30 mg of very pure enzyme from 51 of cell
      culture. At near zero L-ornithine, the 13C kinetic isotope effect was 1.0095, at
      high levels of L-ornithine (86 mM) the 13C kinetic isotope effect was unity, and
      0.83 mM ornithine was found to eliminate half the isotope effect. These results
      are indicative of an ordered kinetic mechanism in which carbamyl phosphate binds
      to the enzyme before L-ornithine. Similar experiments were performed using the
      slow substrate L-lysine in place of L-ornithine. At 90 mM L-lysine the 13C
      kinetic isotope effect was large, 1.076. This value is most likely the intrinsic
      kinetic isotope effect with this substrate, and the chemistry of the enzyme
      catalyzed reaction has become rate limiting.

PMID- 9540806
TI  - 6-Tetrahydrobiopterin functions as a UVB-light switch for de novo melanogenesis.
AB  - (6R)-L-erythro 5,6,7,8-tetrahydrobiopterin (6-BH4) and its 7-isomer (7-BH4)
      function as uncompetitive inhibitors of human and mushroom tyrosinases.
      Stoichiometry for the binding of [3H]-labeled 6-BH4 to both tyrosinases has been
      established as 1:1. Stable complexation of 6-BH4 to tyrosinase appears to involve
      a hydrophilic conserved glutamic acid (Glu131) with a pKa = 4.7. Photo-oxidation
      by UVB-light and O2 reverses the inhibition of tyrosinase by 6-BH4 and 7-BH4 with
      the 6-BH4/tyrosinase complex being four-fold more photolabile than 7
      BH4/tyrosinase. The photo-oxidation of 6-BH4 by UVB-light can be assessed
      spectrophotometrically with this reaction yielding 7,8-dihydroxanthopterin as the
      final product, 7,8-Dihydroxanthopterin neither binds to nor inhibits tyrosinase.
      By contrast, UVA light does not catalyze the photodegradation of 6-BH4. Taken
      together, our results indicate that the photo-oxidation of the
      tetrahydrobiopterins by UVB may represent a photo-switch in the regulation of
      tyrosinase activity to promote de novo melanogenesis.

PMID- 9540807
TI  - Cooperativity between trimers of the hexameric glutamate dehydrogenase from
      Clostridium symbiosum.

PMID- 9540809
TI  - Fruit fly "leukemia".

PMID- 9540808
TI  - Regeneration and cancer.

PMID- 9540810
TI  - The ErbB-2/HER2 oncogenic receptor of adenocarcinomas: from orphanhood to
      multiple stromal ligands.
AB  - Extensive clinical and biochemical evidence implicates ErbB-2, a transmembrane
      tyrosine kinase related to growth factor receptors, in the development,
      metastasis, and resistance to therapy of multiple, common human carcinomas.
      Previous attempts to uncover an ErbB-2-specific ligand led to isolation of the
      neuregulin (NRG) family, but these ligands, like all other growth factors with an
      EGF-like motif, only indirectly active ErbB-2. On the other hand, biochemical and
      genetic evidence suggest a non-autonomous function of ErbB-2 in an interactive
      ErbB signaling network. Accordingly, the oncoprotein acts as a shared signaling
      subunit of primary growth factor receptors. By stabilizing heterodimers with
      other ErbB proteins, ErbB-2 prolongs and enhances signal transduction by a large
      group of stroma-derived growth factors. Furthermore, we have proposed a model in
      which all ErbB-2 ligands are bivalent and bind to ErbB-2 with low affinity,
      following high affinity binding to a primary receptor with which ErbB-2 is
      heterodimerized. Thus the presence of ErbB-2 in relevant ErbB heterodimeric
      structures on the surfaces of certain epithelial tumor cells can amplify signals
      arising from the binding of stromal ErbB ligands. This effect, in turn, may
      promote the growth of carcinoma cells.

PMID- 9540811
TI  - Cancer of the central nervous system. Review of an AACR special conference in
      cancer research with the joint section on tumors of the AANS/CNS (San Diego, CA,
      June 7-11, 1997).

PMID- 9540812
TI  - 11th European Cell Cycle Conference: April 23-26, 1997, Gardone Riviera (Italy)
      and Symposium on Cell Cycle Regulation (17th International Congress of
      Biochemistry and Molecular Biology): August 24-29, 1997, San Francisco, CA.
AB  - In the following pages I have summarized some of the findings presented at two
      recent 'cell cycle gatherings'. I have focused on those topics which in my
      opinion represent a substantial advancement in our understanding of the cell
      cycle regulatory pathways.

PMID- 9540813
TI  - Molecular genetics of cancer: second joint conference of the American Association
      of Cancer Research and the European Association for Cancer Research, September 9
      13, 1997.

PMID- 9540814
TI  - Correlation between stationary phase survival and acid trehalase activity in
      yeast.
AB  - The levels of two trehalose hydrolysing enzymes, acid trehalase (AT) and neutral
      trehalase (NT), have been investigated in Candida utilis at different stages of
      growth; in complete contrast to Saccharomyces cerevisiae, significant AT activity
      appears to be absent at all stages of growth studied in C. utilis. In addition,
      presence of only very low amounts of iso-aspartyl methyl transferase (IMT)
      activity at the onset of stationary phase and lower survival ability in early
      stationary phase in contrast to that of S. cerevisiae lend support to the ideas
      that (a) lower degree of survival of C. utilis in the stationary phase may be a
      direct consequence of inability to mobilise stored trehalose due to absence of
      intracellular AT and reduced levels of IMT activities and (b) trehalose may have
      a dual role vis-a-vis stress resistance in yeasts.

PMID- 9540815
TI  - A Xenopus cysteine string protein with a cysteine residue in the J domain.
AB  - A cDNA clone encoding a Xenopus cysteine string protein (Xcsp) was isolated and
      sequenced. The deduced primary sequence of Xcsp is very similar to other
      vertebrate csps with the exception of a cysteine residue that lies outside of the
      cysteine-string domain. This cysteine residue replaces a serine that is highly
      conserved among vertebrate csps, and thus may be of functional importance. Xcsp
      mRNA appears as a 4.6 kb species on Northern analysis, and immunoblot of Xenopus
      brain membranes reveals a single, 35 kDa Xcsp that can be deacylated, like other
      csps.

PMID- 9540816
TI  - Evolution and regulatory role of the hexokinases.

PMID- 9540817
TI  - Novel cellular determinants for reversal of multidrug resistance in cells
      expressing P170-glycoprotein.
AB  - The newly synthesized calcium channel blocker, Ro44-5912, significantly
      potentiates doxorubicin (Dox)-induced cytotoxicity at non-cytotoxic
      concentrations in Dox-resistant human ovarian cell line, A2780/DX5,
      overexpressing P170-glycoprotein (Pgp). Induction of DNA single- and double
      strand breaks (ssbs and dsbs) was measured using alkaline elution and constant
      field gel electrophoresis (CFGE) assays. The results indicate that potentiation
      of the cytotoxicity of Dox by Ro44-5912 was accompanied by significant increases
      in both, Dox-induced DNA ssbs and dsbs in the resistant cells. Pulsed-field gel
      electrophoresis (PFGE) analysis showed that Dox induced DNA fragments in the 50
      800 kilobase (kb) and 0.8-5.7 megabase (Mb) ranges. The majority of the newly
      synthesized DNA fragments were in the 50-800 kb range. Ro44-5912 treatment
      resulted in significant potentiation of DNA fragmentation in the 50-800 kb range
      with a minor increase in 0.8-5.7 Mb DNA fragments, suggesting that the modulator
      functions by potentiating nascent DNA fragmentation in the resistant cells.
      Exposure to Dox with Ro44-5912 was associated with a prolonged blockage of cells
      in the S-phase. In contrast, exposure to Dox alone resulted in temporary blockage
      of cells in G2/M phase (approximately 24 h) followed by restoration of cell
      proliferation and normal DNA histograms at 48 h after 2 h drug exposure.
      Incorporation of BrdUrd by flow cytometric analysis was inhibited by Dox in the
      presence of Ro44-5912, showing that there is a block of DNA replication. An
      increased damage in newly synthesized DNA could concur with a blocked DNA
      replication. Moreover, slowing progression through the S-phase in cells exposed
      to Dox in combination with Ro44-5912 is accompanied by increased sensitivity of
      Dox poisons, indicating a correlation of specific S-phase perturbation with the
      reversal of Dox resistance by Ro44-5912 in cells expressing Pgp. The results
      suggest that drug-induced augmentation of nascent DNA fragmentation and specific
      cell-cycle perturbation are potentially important molecular determinants for
      reversal of multidrug resistance in addition to restoration of intracellular drug
      retention.

PMID- 9540818
TI  - Nonsteroidal anti-inflammatory drugs, short-chain fatty acids, and reactive
      oxygen metabolism in human colorectal cancer cells.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) and short-chain fatty acids are
      effective suppressors of colorectal cancer that may work in part by accentuating
      apoptosis of transformed cells. Since reactive oxygen species (ROS) can play an
      important role in regulating cell growth and cell death, we determined the effect
      of the NSAIDs indomethacin and salicylic acid, and the short-chain fatty acids
      butyrate and propionate on ROS metabolism in the HT-29 human colorectal carcinoma
      cell line. We find that all of these agents increase cellular peroxide
      generation, as determined by two independent assays. Arachidonic acid was also
      found to increase ROS generation, and could synergize with indomethacin in this
      reaction. The NSAIDs and short-chain fatty acids under study all possess a
      carboxyl group, and this carboxyl group is essential for salicylic acid's ability
      to increase ROS production. Although the two NSAIDs examined increase peroxide
      production, they were both found to suppress superoxide generation by vitamin K3
      (menadione), a redox cycling compound similar to those found in the colon. The
      short-chain fatty acids did not have this activity. The ability of these NSAIDs
      and short-chain fatty acids to alter cellular ROS metabolism may contribute to
      their chemopreventive activity.

PMID- 9540819
TI  - Identification of a distinct antibacterial domain within the N-lobe of
      ovotransferrin.
AB  - We have evaluated the bactericidal activity of hen ovotransferrin (OTf), which
      was found to operate regardless of its iron-deprivation properties, with the
      objective of isolating the bactericidal domain. The amino-terminal half-molecule
      (N-lobe, residues 1-332) of OTf, isolated by trypsin-nicking, retained the
      bactericidal activity independently of iron-deprivation, but not the carboxyl
      terminal half-molecule (C-lobe, residue 342-686), suggesting the presence of a
      bactericidal domain within the N-lobe of the molecule. Specific cleavage at the
      aspartyl residues of OTf, by diluted-acid procedure, yielded fairly large
      peptides, whereas proteolysis for 150 min produced the strongest bactericidal
      peptides mixture. The bactericidal domain was purified from the active
      hydrolysate by gel filtration and reversed-phase HPLC and showed activity against
      S. aureus as well as E. coli K-12. Electrophoretic analysis on tricine-SDS-PAGE
      revealed a bactericidal peptide with an average M(r) of 9900 Da under non
      reducing conditions. In combination with the specificity of cleavage (Asp-X) and
      the molecular mass, its N-terminal microsequencing corresponded to a cationic
      peptide consisting of 92 residues located within the 109-200 sequence of the N
      lobe of OTf, containing three intrachain disulfide bridges, featuring a common
      structural motif occurs in the N-lobes of transferrins for which the sequence is
      available. Two of the disulfides (C160-C174 and C171-C182) form surface exposed
      cringle bridges lying on the opposite side of the iron-binding site from the
      interdomain cleft and showing marked sequence homology to insect defensins, which
      are blockers of the voltage-dependent K+ channels. The peptide lost antibacterial
      activity when its disulfide bonds were reduced, indicating the importance of its
      tertiary structure for the exertion of antibiotic activity.

PMID- 9540820
TI  - Ganglioside composition of GH3 cells: enhancement of fucoganglioside expression
      by estradiol, epidermal growth factor and insulin.
AB  - The GH3 cell line, a bipotential cell line secreting both prolactin (PRL) and
      growth hormone (GH), is a useful model for investigating GH/PRL cell lineage
      differentiation and anterior pituitary adenoma formation. In this study, we
      investigated the ganglioside composition of GH3 cells and identified two
      fucogangliosides as the major gangliosides expressed by these cells. Analyses by
      DEAE-Sephadex A-25 and thin-layer chromatography (TLC) revealed that the GH3
      cells contained two major gangliosides, designated FG1 and FG2, respectively.
      Their structures were identified by fast atom bombardment mass spectrometry and
      proton nuclear magnetic resonance spectrometry: FG1 is IV2FUc alpha,II3NeuAc
      GgOse4Cer and FG2 is IV2FUc alpha,IV3Gal alpha,II3NeuAc-GgOse4Cer. Expression of
      these fucogangliosides was enhanced by chronic treatment with 17 beta-estradiol
      (1 nM), epidermal growth factor (10 nM) and insulin (300 nM), which induced
      differentiation of GH3 cells to normal PRL-secreting cells. Interestingly,
      immunocytochemistry and flow cytometry revealed that the increased expression of
      these gangliosides reflected a quantitative change inside the cells but not on
      the cell surface. These results suggest that the intracellular distribution of
      fucogangliosides is closely related to the differentiation of GH3 cells.

PMID- 9540821
TI  - A murine specific splicing variant of the acetylcholine receptor epsilon-subunit
      gene transcript.
AB  - The acetylcholine receptor (AChR) is an ion channel involved in signal
      transmission from motorneuron to skeletal muscle. We describe here a murine
      specific splicing variant of the epsilon subunit of the AChR (epsilon s), which
      lacks exon 5 epsilon s has a truncated extracellular domain which may affect the
      physiological characteristics of the resulting AChR channel.

PMID- 9540822
TI  - Conjugation of ubiquitin-like polypeptide to intracellular acceptor proteins.
AB  - Monoclonal nonspecific suppressor factor (MNSF), a lymphokine produced by a
      murine hybridoma, was originally found to inhibit the generation of LPS-induced
      immunoglobulin secreting cells. MNSF comprises of MNSF beta, an isoform of MNSF,
      and the other isoform, MNSF alpha. Ubiquitin-like segment (Ubi-L) of MNSF beta
      shows MNSF-like activity. Ubi-L (7.8 kDa) has 36% homology with 8.5 kDa
      ubiquitin. GST-Ubi-L was labeled with 125I by the chloramine T method and tested
      for its conjugation to acceptor in splenocyte lysates. 125I-GST-Ubi-L conjugation
      on SDS-PAGE showed heterogeneous bands including 95 kDa GST-Ubi-L conjugation in
      the splenocyte, but not reticulocyte lysates. The Ubi-L adduct appeared to be
      MNSF-related molecule because anti-MNSF monoclonal antibody (mAb) recognized the
      95 kDa band. The pattern of the conjugations was different from that seen in
      ubiquitination. Unlabeled GST-Ubi-L inhibited the conjugations, while ubiquitin
      did not. alpha-Lactalbumin, one of the target proteins for ubiquitination, failed
      to conjugate to GST-Ubi-L. In addition, covalent conjugation of ubiquitin to
      reticulocyte lysates was also interfered by GST-Ubi-L. These results suggest that
      Ubi-L may conjugate to acceptor proteins in a similar, but not in the same way as
      ubiquitination, and might play an important role in lymphoid cells.

PMID- 9540823
TI  - Acrosome reaction inactivation in sea urchin sperm.
AB  - Acrosome reaction inactivation (ARI) is a process that renders sperm irreversibly
      refractory to the egg jelly (the natural inducer of the acrosome reaction, AR).
      This process triggered by the egg jelly, is associated with an increase in
      [Ca2+]i. However, we show here that a rise in [Ca2+]i alone is not sufficient to
      induce ARI, since artificially increasing [Ca2+]i with either an ionophore or
      rising external pH, does not trigger ARI. Contrary to the AR which strictly
      requires Ca2+, ARI can be triggered almost equally well by Sr2+. On the other
      hand, Mn2+ inhibits ARI and, as we showed earlier, does not affect AR. These
      observations indicate that the mechanisms involved in ARI differ from those
      leading to AR. In addition, we report here that high external pH (a non
      physiological inducer of AR) triggers the AR in previously inactivated sperm by
      opening the same Ca2+ channels activated by the egg jelly. Considering that the
      opening of Ca2+ channels is one of the earliest responses triggered by the egg
      jelly and that ARI requires the egg jelly receptor to be activated, we have
      concluded that ARI involves the uncoupling between the egg jelly receptor and
      Ca2+ channels. Furthermore, intracellular pH (pHi) determinations, in the
      presence or absence of ionomycin to substitute for the uncoupled Ca2+ channels,
      indicate that pHi regulation is also impaired in inactivated sperm. In
      conclusion, ARI is a manifestation of the uncoupling of the egg jelly receptor
      from the different ion transport systems required for the acrosome reaction.

PMID- 9540824
TI  - Mastoparan induces an increase in cytosolic calcium ion concentration and
      subsequent activation of protein kinases in tobacco suspension culture cells.
AB  - Mastoparan induced a transient elevation of cytosolic free Ca2+ concentration
      ([Ca2+]cyt) in tobacco suspension culture cells. The mastoparan-induced [Ca2+]cyt
      elevation was inhibited by 8-(N,N-diethylamino)-octyl 3,4,5-trimethoxybenzoate
      HCl and neomycin but not by depletion of extracellular Ca2+, suggesting that the
      elevation was the result of Ca2+ release from the intracellular stores caused by
      stimulation of phosphoinositide turnover. Hydrogen peroxide which has been shown
      to induce an oxidative burst in soybean cells by mastoparan treatment [L.
      Legendre, P.F. Heinstein, P.S. Low, Evidence for participation of GTP-binding
      proteins in elicitation of the rapid oxidative burst in cultured soybean cells,
      J. Biol. Chem., 267 (1992) 20140-20147], also induced a transient [Ca2+]cyt
      elevation in the tobacco cells. However, mastoparan did not induce an oxidative
      burst in the tobacco cells. Activation of a 50, a 75 and a 80 kDa protein kinases
      after the mastoparan-induced [Ca2+]cyt elevation was shown by an in-gel protein
      kinase assay. This activation was inhibited by neomycin, suggesting that the
      [Ca2+]cyt elevation is necessary for the mastoparan-induced activation of the
      protein kinases. The activation was inhibited also by pretreatment with
      staurosporine and was sustained by pretreatment with calyculin A, suggesting that
      the protein kinase activity is regulated by protein
      phosphorylation/dephosphorylation. The present report shows that mastoparan
      induces an increase in [Ca2+]cyt without oxidative burst and subsequent
      activation of protein kinases in tobacco cells.

PMID- 9540825
TI  - Isolation of a cDNA encoding mouse DNA topoisomerase III which is highly
      expressed at the mRNA level in the testis.
AB  - A cDNA (mTOP3) encoding mouse DNA topoisomerase III (topo III) was cloned using
      the human TOP3 cDNA as a probe. The deduced amino acid sequence of mouse topo III
      showed 86.8% identity with that of human topo III. Mouse TOP3 mRNA was highly
      expressed in the testis in comparison with other tissues. The TOP3 mRNA level in
      the testis increased slightly 14 days after birth and showed a marked increase in
      17 days, times when the cells in pachytene phase begin to appear and increase in
      number.

PMID- 9540826
TI  - Isolation and expression of a human SRY-related cDNA hSOX20.
AB  - SOX is a family of genes related to the testis-determining gene, SRY. We have
      isolated and sequenced an hSOX20 cDNA from a cell line of human embryonic
      carcinoma. This cDNA contains an open reading frame (ORF) encoding 233 amino
      acids. The protein encompasses an SRY-type HMG box exhibiting strong homologies
      to those of mouse Sox15 and Sox16. Various adult and fetal tissues were tested
      for hSOX20 mRNA by Northern analysis. Its expression is restricted to the fetal
      testis and the size of the transcript is 1.5 knt. Electrophoretic mobility shift
      assay indicated that recombinant hSOX20 polypeptide is capable of binding to
      AACAAT sequence.

PMID- 9540827
TI  - Regulated tRNA import in Leishmania mitochondria.
AB  - The genes for three new tRNA and a 5S RNA were identified from a genomic DNA
      clone of 917 nucleotide pairs from the protozoon Leishmania tarentolae. They were
      encoded in the following order. The transcriptional directions and anticodons are
      in parentheses: tRNA(Val) (CAC-->)-5SRNA (-->)-tRNA(His) (<--GUG)-tRNA(Phe) (GAA-
      >). The tRNA(His) and tRNA(Phe) sequences have not been reported previously in
      trypanosomatid organisms. By northern analysis, tRNA(Val) and tRNA(Phe) were
      equally distributed between the cytosol and mitochondria, while tRNA(His) was
      less abundant in mitochondria than in the cytosol. Accordingly, the latter tRNA
      is classified as Import restricted (Impr). As shown before, 5S RNA was not
      imported. Recently, Mahapatra and Adhya [S. Mahapatra, T. Ghosh, S. Adhya, Nucl.
      Acids Res. 22 (1994) 3381-3386; S. Mahapatra, S. Adhya, J. Biol. Chem. 271 (1996)
      20432-20437] have developed an in vitro import system in Leishmania and suggested
      that the D-loop sequence could serve as the import determinant. We examined all
      available tRNA gene sequences in trypanosomatids but found no apparent consensus
      within the D-loop that might account for tRNA-import regulation.

PMID- 9540828
TI  - Cloning and sequencing of the cDNA encoding human neurotrypsin.
AB  - cDNA clones encoding human neurotrypsin have been isolated from a human fetal
      brain cDNA library using a PCR-amplified probe. The assembled cDNA sequence
      contains a 2625 bp open reading frame encoding a multidomain serine protease with
      an overall sequence identity of 82.5% to murine neurotrypsin. Surprisingly, the
      human neurotrypsin exhibits an additional scavenger receptor cysteine-rich
      repeat.

PMID- 9540829
TI  - Nucleotide sequence of the sspE genes coding for gamma-type small, acid-soluble
      spore proteins from the round-spore-forming bacteria Bacillus aminovorans,
      Sporosarcina halophila and S. ureae.
AB  - The single sspE genes coding for gamma-type small, acid-soluble spore proteins
      (SASP) of three round-spore-forming bacteria, Bacillus aminovorans, Sporosarcina
      halophila and S. ureae, have been cloned and sequenced. While the deduced amino
      acid sequences of these three gamma-type SASP show clear homology to those from
      six Bacillus species that do not form round spores, there are no residues
      conserved completely among the 9 sequences known. In addition, the 139 residue B.
      aminovorans protein is 35 residues larger than any other while the 60 residue S.
      halophila protein is one of the smallest. These data suggest that the sspE genes
      have been under little selective pressure in recent evolutionary time.

PMID- 9540830
TI  - Cloning and characterization of the human RNA polymerase I subunit hRPA40.
AB  - The cloning of the human RNA polymerase I 40 kDa subunit, and the comparison of
      its amino acid sequence to other related RNA polymerase subunits are described.
      The amino acid sequence of hRPA40 has high homology to the mouse RNA polymerase I
      40 kDa subunit (93%), to two Arabidopsis thaliana subunits (47%), the yeast RPC40
      subunit (46%) and the human RNA polymerase II hRPB33 subunit (40%). Southern blot
      analysis shows that this gene is single copy and Northern blot analysis indicates
      that the mRNA of 1.3 kb is expressed in different cell types.

PMID- 9540831
TI  - Structure and expression of the human ubiquitin fusion-degradation gene (UFD1L).
AB  - We report the genomic organization, RNA and protein expression patterns of the
      gene encoding for the human homolog of the yeast ubiquitin fusion-degradation
      protein-1 (UFD1L). This enzyme is involved in a ubiquitin-dependent proteolytic
      pathway (UFD), firstly described in yeast. The human UFD1L gene is organized into
      12 exons ranging in size from 33 to 161 bp. Sequence analysis of the 5'-flanking
      region of the gene revealed a high GC content, multiple CCAAT-binding motifs,
      CREB, CFT, and AP-2 sites. RNA transcripts were detected in all tissues and cell
      lines examined, including thymus, thymocytes, T- and B-cells, fibroblasts,
      chorionic villi, and amniocytes. In Western blot, the UFD1L antibody demonstrated
      the presence of multiple protein isoforms in all the tested tissues. Expression
      profile and promoter characteristics suggest UFD1L is a housekeeping gene with
      implications in the pathogenesis of DiGeorge/velo-cardio-facial syndrome, due to
      22q11.2 deletions.

PMID- 9540832
TI  - Identification, cloning and sequence of the Aspergillus niger areA wide domain
      regulatory gene controlling nitrogen utilisation.
AB  - The gene encoding the positive-acting regulator of nitrogen metabolite repression
      (AREA) has been cloned and characterised from the industrially important
      filamentous fungus Aspergillus niger. The deduced amino acid sequence has an
      overall level of identity with its homologues from other fungal species which
      varies between 32 and 72%. This gene (areAnig) complements the A. nidulans areAr
      18 loss-of-function mutation. Sequences upstream of the structural gene contain
      several putative GATA-type zinc finger protein-binding motifs. Northern analysis
      indicates the synthesis of multiple transcripts, the major species being
      approximately 2.95 kb and 3.1 kb. Maximal expression of areAnig is observed under
      conditions of nitrogen starvation and is mainly due to an increase in the level
      of the shorter transcript.

PMID- 9540833
TI  - A hypothesis on the mechanism of translational initiation.

PMID- 9540834
TI  - Contribution of proximal promoter elements to the regulation of basal and
      differential glutathione S-transferase P1 gene expression in human breast cancer
      cells.
AB  - Glutathione S-transferase P1 (GST P1-1) is normally expressed exclusively in
      estrogen receptor negative (ER-) but not receptor positive (ER+) cultured breast
      cancer cells. We examined the role of proximal promoter elements in GST P1 gene
      expression in MCF7 (ER+, GST P1-) and HS578T (ER-, GST P1+) breast cancer cells.
      Transient transfection of GST P1 promoter-CAT reporter genes confirmed that the
      GST P1 TRE (-69 to -60) and the adjacent distal GC box (-56 to -51) are required
      for basal promoter activity in both cell lines. Other studies identified
      differences in the GST P1 promoter activity and DNA-protein interactions between
      the two cell lines. Electrophoretic mobility shift assay revealed a protein-TRE
      interaction that is unique to nuclear proteins derived from GST P1 expressing
      HS578T cells. Furthermore, a putative silencer region contained within sequences 
      130 to -70 selectively reduced GST P1 promoter-CAT reporter gene expression in
      MCF7 but not HS578T cells. While this cell-line specific silencer contributed to
      the level of GST P1 promoter activity observed in the two cell lines, analysis of
      cells stably transfected with a novel genomic GST P1 minigene vector established
      that the silencer is insufficient to completely repress GST P1 transcription in
      ER+, MCF7 cells that do not normally express endogenous GST P1.

PMID- 9540835
TI  - Induction of a subgroup of acute phase protein genes in mouse liver by
      hyperthermia.
AB  - We have demonstrated that two members of the acute phase reactant family of
      positively regulated genes, alpha 1-acid glycoprotein (AGP-1 and AGP-2) and C
      reactive protein (CRP) are induced by hyperthermia, while two others, the serum
      amyloid A (SAA) and alpha 1-antitrypsin (AT) genes, are not. Albumin (ALB), a
      negative acute phase reactant gene, is also induced by hyperthermia. The AGP-1,
      AGP-2, and CRP genes require glucocorticoids, but not IL-6, IL-1 beta or TNF
      alpha in response to hyperthermia. As with LPS, the C/EBP beta mRNA levels
      increased, while the C/EBP alpha mRNA levels decreased in response to LPS. In
      contrast to the LPS response, C/EBP delta was unchanged. Protein pool levels and
      DNA-binding activities of the 35 and 20 kDa C/EBP beta isoforms increase, whereas
      protein pool levels of the 42 kDa C/EBP alpha decrease and the 30kDa remained
      high. These studies suggest that the synthesis of specific C/EBP alpha and C/EBP
      beta isoforms is induced by hyperthermia, and that the regulation of the AGP-1
      and AGP-2 genes during heat stress may involve one of these isoforms. The
      difference between the responses to hyperthermia and LPS is that the former, may
      not involve the participation of cytokines. Furthermore, since cis-acting heat
      shock elements (HSE) are located in the promoter regions of the ALB, CRP, and
      C/EBP beta genes, these regulatory sequences may be involved in the in vivo
      activation of these genes by hyperthermia.

PMID- 9540836
TI  - Alternative splicing in the Caenorhabditis elegans DNA topoisomerase I gene.
AB  - 5'-end cDNA fragments of the Caenorhabditis elegans DNA topoisomerase I gene were
      obtained by rapid amplification of the cDNA ends from C. elegans mRNAs. The
      presence of a SL1 sequence at the 5'-terminus of the cDNA sequence suggested
      trans-splicing of the pre-mRNA. By comparing the complete cDNA sequence with the
      genomic lambda DNA clones, the gene structure composed of five exons was
      established. Alternative splicing deleting the second exon was observed in the
      cDNA fragments obtained by a gene-specific reverse transcription followed by
      polymerase chain reactions. The shorter mRNA missing the second exon was
      expressed at all the developmental stages, while the full-length mRNA was present
      only in embryos.

PMID- 9540837
TI  - A thermophilic nitrate reductase is responsible for the strain specific anaerobic
      growth of Thermus thermophilus HB8.
AB  - T. thermophilus HB8 contains a nitrate reductase gene cluster which is absent
      from closely related strains. This cluster encodes 4 ORFs (a-d) similar in
      organization and protein sequence to those encoded by respiratory nitrate
      reductase operons (narGHJI) of Escherichia coli, Bacillus subtilis, Pseudomonas
      fluorescens, and Thiosphaera pantothropha. The highest similarity is shown
      between the proteins encoded by the ORFa, ORFb and ORFd, and the structural
      components of the mesophilic nitrate reductases NarG (alpha), NarH (beta), and
      NarI (gamma) proteins, whilst ORFc encodes a protein which showed lower
      similarity to NarJ, a protein of unknown function encoded between narH and narI
      genes in all the nar cluster so far sequenced. This T. thermophilus HB8 narGHJI
      cluster is strongly induced by the combined effect of nitrate and low oxygen
      concentration, giving rise to the synthesis of an enzyme whose optimal
      temperature and pH was determined to be 80 degrees C, and pH 10, respectively. We
      also demonstrate that insertional inactivation of the narG and narH genes of this
      cluster results in strictly aerobic mutants, showing its sole responsibility in
      the strain specific ability of T. thermophilus HB8 to grow anaerobically.

PMID- 9540838
TI  - Synthesis, antimicrobial activity and gene structure of a novel member of the
      dermaseptin B family.
AB  - Dermaseptins are a family of cationic (Lys-rich) antimicrobial peptides that are
      abundant in the skin secretions of the arboreal frogs Phyllomedusa bicolor and P.
      sauvagii. In vitro, these peptides are microbicidal against a wide variety of
      microorganisms including Gram-positive and Gram-negative bacteria, yeasts,
      protozoa and fungi. To date, 6 dermaseptin B mature peptides, 24-34 residues
      long, 2 dermaseptin B cDNAs and 2 gene sequences have been identified in P.
      bicolor. To assess dermaseptin related genes further, we screened a P. bicolor
      genomic library with 32P-labeled cDNAs coding either for prepro-dermaseptins B1
      or B2 (adenoregulin). A gene sequence was identified that coded a novel
      dermaseptin B, termed Drg3, which exhibits 23-42% amino acids identities with
      other members of the family. Analysis of the cDNAs coding precursors for several
      opioid and antimicrobial peptides originating from the skin of various amphibian
      species revealed that the 25-residue preproregion of these preproforms are all
      encoded by conserved nucleotides encompassed by the first coding exon of the Drg3
      gene. Synthetic dermaseptin Drg3 exhibited a bactericidal activity towards
      several species of mollicutes (wall-less eubacteria), firmicutes (Gram-positive
      eubacteria), and gracilicutes (Gram-negative eubacteria), with minimal inhibitory
      concentrations (MICs) ranging from 6.25 to 100 microM. Experiments performed on
      Acholeplasma laidlawii cells revealed that this peptide is membranotropic and
      that if efficiently depolarizes the plasma membrane.

PMID- 9540839
TI  - Biogenesis of L-glyceric aciduria, oxalosis and renal injury in rats simulating
      type II primary hyperoxaluria.
AB  - Tracer experiments in rats mimicking type II primary hyperoxaluria, with an
      expanded intracellular pool of hydroxypyruvate, showed that the excess formation
      of oxalate did not originate from its immediate precursor glyoxylate. In these
      animals, the hepatic and kidney activities of oxalate synthesising enzymes such
      as lactate dehydrogenase and glycolate oxidase were normal, but tissue lipid
      peroxidation was significantly higher. In vitro experiments established that in a
      mild alkaline solution, hydroxypyruvate underwent auto-oxidation to form oxalate
      and H2O2 and also inhibited lactate dehydrogenase and glycolate oxidase from
      oxidising glyoxylate to oxalate. On the basis of the experimental evidence, we
      suggest that in type II primary hyperoxaluria, the accumulating hydroxypyruvate
      could reduce the intracellular pool of glyoxylate and on ageing, give rise to
      excess oxalate and H2O2, to cause oxalosis in the former and free radical
      mediated-cell injuries in the latter.

PMID- 9540840
TI  - Non-conventional modification of low density lipoproteins: chemical models for
      macrophage recognition of oxidized LDL.
AB  - To define the structural and chemical criteria governing recognition of oxidized
      LDL (oxLDL) by mouse peritoneal macrophages (MPM), we exposed LDL to novel
      chemical modification agents that induce defined neutralizing and non
      neutralizing alterations of lysine as models for distinct apoB adducts present in
      oxLDL. We found some exceptions to the usual notion that neutralization of lysine
      positive charges is the principal determinant governing MPM recognition. In
      addition, competitive binding experiments using chemically modified 125I-LDL
      preparations revealed that, whereas some modifications engendered recognition
      principally by the classical scavenger receptor class A (SRA), as seen for
      acetylated LDL (acLDL), chemical models of advanced aldehydic modifications of
      LDL led instead to MPM uptake mainly by oxLDL receptors distinct from SRA.

PMID- 9540841
TI  - Molecular analysis of a filamentous phage (fsl) of Vibrio cholerae O139.
AB  - A filamentous bacteriophage from Vibrio cholerae O139 strain A1-4450 was isolated
      (fsl). The phage fsl had a ssDNA genome and dsDNA as a replicative form (RF) in
      lysogenic host cell. The DNA sequence of fsl RF was determined. It consisted of
      6340 bp and had a G + C content of 43.5%. Fifteen possible ORFs were found in
      fsl. One of them, ORF384, was estimated to encode 384 amino acid residues (44.6
      kDa) and had homologous regions with the zot gene of V. cholerae and gene I of
      the coliphage group. ORF104, located upstream of ORF384, was homologous to gene
      93 protein of Pf3 (filamentous phage of Pseudomonas sp.) corresponding to gene VI
      of coliphage. Other than ORF384 and ORF104, the ORF81, ORF44, ORF29, and ORF193
      were speculated to correspond to gene V, gene VII, gene IX, and gene III,
      respectively, in the order as reported on f1 phage.

PMID- 9540842
TI  - Lipid peroxidation, antioxidant protection and aging.
AB  - The free radical hypothesis of aging proposes that deleterious actions of oxygen
      derived radicals are responsible for the functional deterioration associated with
      aging. Because cellular membranes house the production apparatus of these
      radicals and because membranes suffer great damage from these radicals,
      modification of membrane lipids has been proposed to play a major role in the
      process of aging. Although the relationships between lipid peroxidation and aging
      have been investigated extensively, the studies have produced conflicting
      results. Increased lipid peroxidation and decreased antioxidant protection
      frequently occur, but they are not universal features of aging. Instead, age
      dependent changes in these parameters appear to be species-, strain-, sex- and
      tissue specific. Potential correlations between lipid peroxidation and transition
      metal concentrations or between lipid peroxidation and declining antioxidant
      protection have been obscured by the contradictory nature of the findings. Future
      studies should focus on new approaches for the measurement in vivo lipid
      peroxidation and on identification of the critical targets of lipid peroxidation.

PMID- 9540843
TI  - Relation between enzyme release and irreversible cell injury of the heart under
      the influence of cytoskeleton modulating agents.
AB  - The effects of agents modulating the cytoskeleton, taxol (microtubuli
      stabilizing), vinblastine (microtubuli destabilizing) and cytochalasin D (actin
      destabilizing) (10(-6) M each) on enzyme and ATP release as well as on
      irreversible cell injury were investigated in isolated perfused hypoxic and
      reoxygenated rat hearts. Enzyme (creatine kinase (CK)) and ATP concentration were
      assayed in the interstitial transudate and venous effluent. Irreversible cell
      injury was determined from trypan blue uptake and nuclear staining (NS) of
      cardiomyocytes in histologic sections. ATP release from nonneuronal cells was
      only detectable in the interstitial transudate and was not significantly altered
      by the agents. In controls total CK release (about 4% of total CK) exceeded the
      percentage of irreversibly injured cells by a factor of 8. Taxol and cytochalasin
      D abolished the hypoxia/reoxygenation induced interstitial CK release and reduced
      total CK release to a highly significant extent. The percentage of irreversible
      injured cells was even more diminished by these agents resulting in a ratio of
      CK/NS of 40. The effect of cytochalasin D apparently is the consequence of
      decreased contractile performance as shown by analogous depression by butonedione
      monoxine (BDM), whereas contractile activity was not altered by taxol.
      Vinblastine had no influence on CK release but increased the number of
      irreversibly injured cells significantly. In conclusion, cytoskeletal elements
      apparently participate in the hypoxia/reoxygenation induced process of release of
      cytosolic enzymes (CK) and irreversible injury in a different way and extent.
      Taxol exhibits a cytoprotective effect in isolated perfused rat hearts as
      evaluated by the extent of enzyme release and irreversible cell injury.

PMID- 9540844
TI  - Ethanol induces the expression of alpha 1(I) procollagen mRNA in a co-culture
      system containing a liver stellate cell-line and freshly isolated hepatocytes.
AB  - To study the fibrogenic action of ethanol in vitro we used a co-culture system of
      freshly isolated hepatocytes and a liver stellate cell line (CFSC-2G) developed
      in our laboratory. Our results show that in this co-culture system ethanol
      induces the expression of alpha 1(I) procollagen mRNA in a dose- and time
      dependent manner. This effect of ethanol was due to its metabolism by alcohol
      dehydrogenase since 4-methylpyrazole prevented the ethanol-mediated increase in
      alpha 1(I) procollagen mRNA. Ethanol was more efficient than acetaldehyde in
      inducing alpha 1(I) procollagen mRNA expression and its effect was protein
      synthesis-independent. Transfection of either hepatocytes or liver stellate cells
      with a reporter gene, chloramphenicol acetyl transferase (CAT), driven by 3700 bp
      of the mouse alpha 1(I) procollagen promoter demonstrated that only LSC expressed
      significant CAT activity and that this activity was enhanced by ethanol. Overall,
      our results suggest that this co-culture system is a useful model to study
      alcohol-induced fibrogenesis in vitro and that mechanisms other than acetaldehyde
      formation may also play an important role in alcohol-induced fibrogenesis.

PMID- 9540845
TI  - Expression of mtDNA and nDNA encoded respiratory chain proteins in chemically and
      genetically-derived Rho0 human fibroblasts: a comparison of subunit proteins in
      normal fibroblasts treated with ethidium bromide and fibroblasts from a patient
      with mtDNA depletion syndrome.
AB  - Although much progress has been made in identifying genetic defects associated
      with mitochondrial diseases, the protein expression patterns of most disorders
      are poorly understood. Here we use immunochemical techniques to describe subunit
      expression patterns of respiratory chain enzyme complexes II (succinate
      dehydrogenase: SD) and IV (cytochrome c oxidase: COX) in cultured cells lacking
      mtDNA (Rho0 cells) derived either chemically by exposure of normal cells to
      ethidium bromide, or genetically in cells derived from a patient with mtDNA
      depletion syndrome. Both control cells and early passage patient-derived cells
      express a normal complement of SD and COX subunit proteins. Ethidium bromide
      treatment of normal cells and in vitro cell proliferation of patient-derived
      cells caused both populations to acquire identical Rho0 phenotypes. As expected,
      they lack mtDNA-encoded subunits COX-I and COX-II. In contrast, nDNA-encoded
      subunits are affected differentially, with some (COX-VIc) lacking and others (COX
      IV, COX-Va, SD 30 and SD 70) maintained at somewhat reduced levels. We suggest
      that the differential stability of nDNA-encoded subunits in the absence of intact
      enzyme complexes is due to the ability of some, but not all, subunits to
      associate as partial complexes in the absence of mtDNA-encoded subunits.

PMID- 9540846
TI  - Deficiency of dihydrolipoamide dehydrogenase due to two mutant alleles (E340K and
      G101del). Analysis of a family and prenatal testing.
AB  - A male child with metabolic acidosis was diagnosed as having dihydrolipoamide
      dehydrogenase (E3) deficiency. E3 activity of the proband's cultured fibroblasts
      and blood lymphocytes was 3-9% of normal, while in the parent's lymphocytes it
      was about 60% of normal. The proband's pyruvate dehydrogenase complex (PDC) and
      the alpha-ketoglutarate dehydrogenase complex activities from cultured skin
      fibroblasts were 12% and 6% of normal, respectively. PDC activity in the parents
      cultured fibroblasts was 25-31% of normal. Western and Northern blot analyses
      showed similar quantities of E3 protein and mRNA in cultured fibroblasts from the
      proband and his parents. DNA sequencing of cloned full-length E3 cDNAs, from the
      proband and the parents, showed two mutations on different alleles of proband
      were inherited from the parents. One mutation is a three nucleotide (AGG)
      deletion, from the mother, resulting in deletion of Gly101 in the FAD binding
      domain. The other mutation is a nucleotide substitution (G to A), from the
      father, leading to substitution of Lys for Glu340 in the central domain. The same
      deletion mutation was found in E3 cDNA from a chorionic villus sample and
      cultured fibroblasts obtained from the mother's subsequent offspring. This
      finding illustrates the possibility of successful prenatal diagnosis of E3
      deficiency utilizing mutations characterized prior to initiation of pregnancy.

PMID- 9540847
TI  - Does oxidative protein damage play a role in the pathogenesis of carbon
      tetrachloride-induced liver injury in the rat?
AB  - Free radicals have been implicated in the pathogenesis of alcohol-induced liver
      injury in humans and carbon tetrachloride (CCl4)-induced liver injury in rats.
      The most extensively studied aspect of free radical induced liver injury is lipid
      peroxidation. Recently it has been found that free radicals can cause oxidative
      damage to cellular proteins and alter cellular function. One such susceptible
      protein is the enzyme glutamine synthase (GS). The chemical effects of CCl4 on
      cell proteins and their biological consequences are not known. Hence, in our
      study, the effect of CCl4 on liver protein oxidation and GS activity were
      investigated and compared with lipid peroxidation. A significant increase in
      liver protein carbonyl content (2-3 fold) and a significant decrease in hepatic
      GS activity (44-57%) were observed. Damage to proteins was rapid in onset and
      increased with time. Acute exposure of rats to CCl4 resulted in an increase in
      hepatic protein carbonyl content and a decrease in hepatic GS within 1 h. In
      cirrhosis of the liver induced by CCl4, the decrease in hepatic GS activity was
      accompanied by a significant increase in plasma ammonia levels. We conclude that
      protein oxidation may play a role in the pathogenesis of CCl4 induced liver
      injury and that the accumulation of oxidised proteins may be an early indication
      of CCl4 induced liver damage.

PMID- 9540848
TI  - Identification of an active site in the antisecretory factor protein.
AB  - The antisecretory factor (AF) is a new regulatory protein, produced in the human
      pituitary gland, which reverses intestinal fluid secretion induced by cholera
      toxin. We have previously described the cDNA-cloning and characterization of the
      expressed gene. The aim of this study was to identify the region responsible for
      the antisecretory activity in the AF-molecule. The recombinant full-length AF has
      an increased ability to inhibit hypersecretion after treatment with trypsin,
      indicating that the activity of AF is achieved by smaller peptide fragments. To
      localize the active region of AF, we expressed truncated forms of the recombinant
      protein and examined their antisecretory activity against cholera toxin-induced
      fluid secretion in rat. Nine recombinant AF peptides and four smaller peptides
      made by solid phase synthesis were tested. Five of the peptides lacked all
      activity, whereas seven of them were highly active, a dose between 4 and 15 pmol
      causing a half-maximal inhibition. All the active peptides contained amino acid
      36-42 of the AF sequence, whereas none of the inactive peptides contained this
      sequence. Our results suggest that the site of the antisecretory activity resides
      in a small region (I)VCHSKTR between position 35 and 42 of the AF molecule.

PMID- 9540849
TI  - Amyloid precursor protein heat shock response in lymphoblastoid cell lines
      bearing presenilin-1 mutations.
AB  - The amyloid precursor protein (APP) gene promoter contains a heat shock element.
      An abnormal APP heat shock response could increase accumulation of A beta, the
      APP metabolite found in Alzheimer's disease amyloid plaques. Since A beta
      production is affected by presenilin-1 (PS-1) mutations, we investigated whether
      basal APP levels or response to heat shock were altered in lymphoblastoid cell
      lines from 8 PS-1 mutation-bearers and 9 control members of Alzheimer's disease
      families. Lymphoblastoid cell lines were incubated at 42 degrees C for 35 min and
      allowed to recover at 37 degrees C for 1, 3, 8, 24 and 48 h. APP mRNA levels,
      quantified using RNA-RNA solution hybridisation, increased significantly at 1 and
      3 h post-heat shock to between 123% and 163% of pre-heat shock (0 h) levels and
      returned to normal by 8 h. Semi-quantitative Western immunoblotting of cell
      lysates using the 22C11 antibody detected two major bands, migrating at
      approximately 145 and approximately 120 kDa. Band optical densities increased
      significantly at 3 h to approximately 155% of 0 h levels, following the increase
      in APP mRNA levels and showing a similar reversibility. APP mRNA and protein
      responses were comparable in the PS-1 mutation-bearing and control cell lines.
      This study shows that both APP mRNA and protein are induced in lymphoblastoid
      cell lines following heat shock and that this response is not affected by PS-1
      mutations which are pathogenic for Alzheimer's disease.

PMID- 9540850
TI  - Alterations in carnitine-acylcarnitine translocase activity and in phospholipid
      composition in heart mitochondria from hypothyroid rats.
AB  - Changes in mitochondrial fatty acid metabolism may underlie the decline in
      cardiac function in the hypothyroid animals. The effect of hypothyroidism on
      fatty acid oxidation, carnitine-acylcarnitine translocase activity and lipid
      composition in rat heart mitochondria has been examined. Rates of mitochondrial
      fatty acid oxidation as well as carnitine-carnitine and carnitine
      palmitoylcarnitine exchange reactions were all depressed in heart mitochondria
      isolated from hypothyroid rats. Kinetic analysis of the carnitine-carnitine
      exchange reaction showed that the hypothyroid state affects the Vmax of this
      process, while having no effect on the K(m) value. Heart mitochondrial inner
      membrane lipid composition was significantly altered in hypothyroid rats.
      Cardiolipin, particularly, was found to decrease (by around 36%). Alterations in
      fatty acid pattern of mitochondrial inner membrane preparations from hypothyroid
      rats were also found. The effects of the hypothyroid state on fatty acids
      oxidation, carnitine translocase activity and phospholipid composition were
      completely reversed by following treatment of hypothyroid rats with thyroid
      hormone. A lower cardiolipin content in the mitochondrial inner membrane offers a
      plausible mechanism to explain the decline in the translocase activity in
      hypothyroidism.

PMID- 9540851
TI  - Dihydropyridine receptor gene expression in skeletal muscle from mdx and control
      mice.
AB  - The expression of isoform-specific dihydropyrine receptor-calcium channel (DHPR)
      alpha 1-subunit genes was investigated in mdx and control mouse diaphragm (DIA)
      and tibialis anterior (TA). RNase protection assays were carried out with a rat
      DHPR cDNA probe specific for skeletal muscle and a mouse DHPR cDNA probe specific
      for cardiac muscle. The level of expression of the gene encoding the cardiac DHPR
      was very weak in TA muscle from both control and mdx mice. Compared to TA, DIA
      expressed mRNA for the cardiac isoform at significantly higher levels, but mdx
      and control mouse DIA levels were similar to one another. In contrast, mRNA
      expression levels for the DHPR skeletal muscle isoform were lower in control DIA
      than TA. However, there was a dramatic increase in the expression for the DHPR
      skeletal muscle isoform in mdx DIA compared with control DIA, reaching the TA
      expression level, whereas dystrophy did not affect TA expression. [3H]-PN200-110
      binding was used to further assess DIA DHPR expression at the protein level. The
      density of binding sites for the probe was not significantly affected in DIA
      muscles of mdx vs. control mice, but it was reduced in older mdx and control
      mice. The increase in DHPR mRNA levels without a consequent increase in DHPR
      protein expression could be secondary to possible enhanced protein degradation
      which occurs in mdx DIA. The altered DHPR expression levels found here do not
      appear to be responsible for the severe deficits in contractile function of the
      mdx DIA.

PMID- 9540853
TI  - Degradation of glycosaminoglycans by reactive oxygen species derived from
      stimulated polymorphonuclear leukocytes.
AB  - The effect of reactive oxygen species (ROS), generated by in vitro stimulation of
      isolated PMN upon the main GAG components of mineralised and non-mineralised
      connective tissues was investigated. PMN were isolated from whole blood and the
      production of the ROS superoxide (O2.-) and hydroxyl radicals (.OH) was
      stimulated by the addition of phorbol myristyl acetate (PMA) and PMA/FeCl3-EDTA
      chelate respectively and their production assessed over a 24 h period. The
      glycosaminoglycans (GAG), hyaluronan, chondroitin 4-sulphate and dermatan
      sulphate, were exposed to the ROS fluxes, incubated at 37 degrees C for 1 h and
      24 h. GAG fragmentation was examined by gel exclusion chromatography and
      modification to hexuronic acid and hexosamine residues determined. Stimulation of
      PMN with PMA resulted in a burst of O2.- production for 1 h, which was sustained
      at a reduced level for 24 h. Fragmentation of GAG was observed for all GAG
      examined. Modification to the GAG was evident, with hyaluronan being more
      susceptible to loss of GAG residues than sulphated GAG. Modification of sugar
      residues increased with the incubation time and loss of the hexuronic acid
      residues was greater than loss of hexosamine residues. Addition of FeCl3-EDTA
      chelate, which led to the generation of .OH and was sustained over the 24 h
      period, demonstrated similar trends of GAG modification although increased
      degradation and loss of hexosamine and hexuronic acid were observed. GAG chains
      are constituents of PGs and their modification is likely to affect the function
      of these macromolecules and be of importance in considering the pathogenesis of
      inflammatory diseases, including periodontal diseases.

PMID- 9540852
TI  - Proteoglycan breakdown from bovine nasal cartilage is increased, and from
      articular cartilage is decreased, by extracellular ATP.
AB  - The addition of ATP, but not ADP or AMP, to the culture media of bovine nasal
      cartilage explants caused an acceleration in the rate of proteoglycan loss from
      the tissue. The ATP-stimulated loss of proteoglycan was not inhibited by the IL1
      receptor antagonist protein, but was partially inhibited by the presence of ADP
      or AMP. The proteolytic events resulting from the presence of ATP were found to
      be similar to those following treatment with IL1, in that inhibitors of the
      cysteine-peptidase cathepsin B, serine-proteinases with trypsin-like specificity,
      and of some of the matrixins, could all prevent proteoglycan loss, which was
      mediated, at least in part, by the action of 'aggrecanase'. In contrast to its
      effects on nasal cartilage, ATP inhibited basal and stimulated proteoglycan
      release from articular cartilage. Both ADP and AMP had no effect on proteoglycan
      release in articular cartilage but enhanced the response to ATP when added
      concurrently. We conclude that extracellular ATP, probably acting via P2
      purinoceptors, stimulates proteoglycan breakdown from bovine nasal cartilage and
      thus, may have a role in diseases which primarily involve destruction of non
      articular cartilage. Extracellular ATP has, in contrast, a chondroprotective
      effect on bovine articular cartilage.

PMID- 9540854
TI  - Inactivation of glyceraldehyde 3-phosphate dehydrogenase by sugars, prednisolone
      21-hemisuccinate, cyanate and other small molecules.
AB  - Diabetes, diarrhoea, renal failure and glucocorticoid therapy have all been
      identified as independent risk factors for cataract. Increased post-translational
      modification of proteins, leading to inactivation of enzymes and induction of
      conformational changes within proteins could result in lens opacification and
      cataract. Aspirin has been associated with many beneficial effects, including
      protection against cataract, in-vivo. alpha-Crystallin has been shown to act as a
      molecular chaperone in-vitro. This lenticular protein prevented the thermal
      aggregation of other lens proteins in-vitro and has sequence and functional
      homology with the small heat shock proteins. Glyceraldehyde 3-phosphate
      dehydrogenase (GAP-DH) is constitutively expressed in tissues and is susceptible
      to chemical modification in-vivo. In-vitro incubations of GAP-DH with sugars,
      cyanate and prednisolone-21-hemisuccinate, all led to significant loss of enzyme
      activity with time in two buffer systems. Rapid inactivation occurred when GAP-DH
      was incubated with fructose 6-phosphate or prednisolone-21-hemisuccinate. Slower
      inactivation was observed when GAP-DH was incubated with fructose, glucose 6
      phosphate or potassium cyanate. Glucose did not inactivate GAP-DH under the
      conditions of our experiments. Aspirin and ibuprofen were shown to inactivate GAP
      DH very rapidly in-vitro. Bovine lenticular alpha-crystallin conferred no
      protection against GAP-DH inactivation. This is the first occasion that alpha
      crystallin has been demonstrated to be unable to protect against inactivation in
      our chemical enzyme inactivation system. This may have implications for the
      susceptibility of lenticular GAP-DH to post-translational inactivation.

PMID- 9540855
TI  - Trypsinogen activation in rat pancreatic acinar cells hyperstimulated by
      caerulein.
AB  - Inappropriate trypsinogen activation is discussed as an early intracellular event
      in the secretagogue-induced model of acute pancreatitis. However, the mechanisms
      by which trypsinogen is activated are not well characterized. In the present
      work, trypsinogen activation was studied in intact acinar cells using bis-(CBZ
      arginyl)-Rhodamine 110 [(CBZ-Arg)2-Rho 110] as a cell-permeant substrate for
      trypsin and also independently via the formation of trypsinogen activation
      peptide (TAP). Preincubation with 10 nM caerulein increased the Rho 110-substrate
      cleavage more than threefold. This proteolytic activity was fully sensitive to a
      benzamidine (BA)-type serine protease inhibitor. The appearance of enzymatic
      activity was paralleled by the formation of TAP. The lack of effect of the high
      molecular soybean trypsin inhibitor indicates an intracellular substrate
      cleavage. The cathepsin B inhibitor CA-074 prevented neither the caerulein
      induced formation of TAP nor the (CBZ-Arg)2-Rho 110-cleaving activity. BA
      inhibited the Rho 110-substrate cleavage and significantly reduced the TAP
      formation. These results show that trypsinogen activation in caerulein
      hyperstimulated acinar cells may occur independently of the activity of cathepsin
      B. On the contrary, the effect of BA suggests the role of a serine protease in
      trypsinogen activation.

PMID- 9540856
TI  - Suppression of NF-kappa B and AP-1 activation by glucocorticoids in experimental
      glomerulonephritis in rats: molecular mechanisms of anti-nephritic action.
AB  - Transcription factors nuclear factor-kappa B (NF-kappa B) and activator protein-1
      (AP-1) play an important role in the induction of pro-inflammatory factors such
      as cytokines and cell adhesion molecules, which could be involved in the
      pathogenesis of glomerulonephritis. We have recently reported the pathogenic
      significance of NF-kappa B activation in experimental glomerulonephritis in rats.
      In this study, we investigated the pathogenic relevance of AP-1 activation in
      nephrotoxic serum (NTS)-induced glomerulonephritis. Increased AP-1 DNA-binding
      activity was detected in nephritic glomeruli by a gel shift assay. The kinetics
      of AP-1 activation was similar to that of NF-kappa B. Activation of both NF-kappa
      B and AP-1 preceded proteinuria, an important pathophysiological parameter for
      glomerulonephritis. Treatment with prednisolone, a glucocorticoid hormone,
      prevented activation of both NF-kappa B and AP-1 in glomeruli and subsequent mRNA
      expression of NF-kappa B- and AP-1-regulated genes. Prednisolone was also
      effective therapeutically and reduced DNA-binding activities of NF-kappa B and AP
      1 which are already activated in nephritic glomeruli. These results suggest that
      activated NF-kappa B and AP-1 may play an important pathogenic role in
      glomerulonephritis and the anti-nephritic action of glucocorticoids may be
      mediated through the suppression of these transcription factors.

PMID- 9540857
TI  - Secondary abnormality of carnitine biosynthesis results from carnitine
      reabsorptional system defect in juvenile visceral steatosis mice.
AB  - We characterized the L-carnitine transport system which is defective in the
      kidney of juvenile visceral steatosis (JVS) mice by using kidney slices and
      carnitine-related compounds, and evaluated the influence of the transport defect
      on the biosynthetic pathway of carnitine. The JVS mouse transport system defect,
      calculated as the difference in the transport activity between control and JVS
      mice, was simulated in control by gamma-butyrobetaine (gamma-BB) and acetyl L
      carnitine. gamma-BB hydroxylase activity in the liver of JVS mice was double that
      of control mice, but the hepatic level of gamma-BB in JVS mice was lower than in
      control mice, suggesting that the conversion of gamma-BB to carnitine is not
      activated in the liver of JVS mice. JVS mice showed higher fractional excretions
      not only of L-carnitine but also of gamma-BB and acetyl L-carnitine than control
      mice, indicating disturbed reabsorption of gamma-BB and acetyl L-carnitine. The
      disturbed reabsorption of gamma-BB in JVS mice is consistent with the fact that
      the amount of urinary gamma-BB in JVS mice was four times that of control. The
      sum of the concentrations of L-carnitine, acetyl L-carnitine and gamma-BB in the
      urine of JVS mice was not significantly different from that of the control,
      suggesting no remarkable increase of biosynthesis of gamma-BB and carnitine in
      JVS mice. All these findings suggest that the carnitine transport system plays a
      role in the transport of gamma-BB and that carnitine deficiency is aggravated by
      the disturbed reabsorption of gamma-BB in the kidney.

PMID- 9540858
TI  - Molecular cloning of acid alpha-glucosidase cDNA of Japanese quail (Coturnix
      coturnix japonica) and the lack of its mRNA in acid maltase deficient quails.
AB  - Acid alpha-glucosidase (GAA) hydrolyzes alpha-1, 4 and alpha-1, 6 glucosidic
      linkages of oligosaccharides and degrades glycogen in the lysosomes. The full
      length GAA I cDNA, pQAM8, was isolated from a cDNA library derived from Japanese
      quail liver. The cDNA is 3569 base pairs long and has an open reading frame
      capable of coding 932 amino acids. The deduced amino acid sequence shares 52%
      identity with human GAA. Transfection of expression vector pETAM8 into COS-7
      cells or acid maltase deficient (AMD) quail embryonic fibroblasts increased the
      level of GAA 20-50-fold. Compared to normal quail, the levels of GAA I mRNA were
      significantly reduced in the muscle, liver, heart, and brain of AMD quails,
      suggesting the GAA deficiency in AMD quail is due to a lack of GAA I mRNA. A
      second GAA II cDNA was identified after probing the cDNA library from the ovarian
      large follicles of quails with a PCR product derived from cultured quail skin
      fibroblasts. This clone having 3.1 kb insert, has GAA activity as well (3 to 10
      fold increase). This cDNA, designated GAA II, predicted an 873 amino acid
      polypeptide showing 63% identity to human GAA and 51% identity to the GAA I. The
      RT-PCR analysis demonstrated that GAA II mRNAs were barely detectable in normal
      tissues, while they were enhanced to higher levels in AMD tissues. These results
      suggest that GAA II expression is up-regulated at the transcription levels, and
      quail GAA gene redundancy performs the same function of satisfying GAA demand at
      the two different phases represented by normal and AMD.

PMID- 9540859
TI  - Telesonography may solve ultrasonography dilemma.

PMID- 9540860
TI  - Perspectives on cat predation studies.

PMID- 9540861
TI  - Staining methods for cytopathologic examination.

PMID- 9540863
TI  - Animal behavior case of the month. A dog was referred for evaluation of
      aggression towards its owner, visitors, and referring veterinarian.

PMID- 9540862
TI  - What is your diagnosis? Dyspnea and bite wounds after an attack by another dog.

PMID- 9540864
TI  - Veterinary careers in the US Public Health Service Commissioned Corps.

PMID- 9540865
TI  - Fee splitting, kickbacks, rebates, and commissions.

PMID- 9540866
TI  - Serologic survey for hantavirus infection in domestic animals and coyotes from
      New Mexico and northeastern Arizona.
AB  - OBJECTIVE: To determine whether animals had serologic evidence of infection with
      Sin Nombre virus (SNV). DESIGN: Prospective serosurvey. SAMPLE POPULATION: Serum
      samples were obtained from 145 cats, 85 dogs, 120 horses, and 24 cattle between
      April 1993 and August 1994 and 54 coyotes between December 1994 and February
      1995. PROCEDURE: Serum samples were analyzed by western immunoblot assays for
      reaction with SNV nucleocapsid antigen. Samples with reactivity to SNV
      nucleocapsid proteins were used to probe multiple-antigen blots containing
      recombinant fusion proteins derived from prototypic hantaviruses. Lung tissue or
      blood clots were used in nested reverse-transcriptase polymerase chain reaction
      assays for a 320-nucleotide portion of the SNV G1 gene. RESULTS: Sera from 4 of
      145 (2.8%) cats and 4 of 85 (3.5%) dogs had trace reactivity to full-length SNV
      encoded nucleocapsid proteins. All samples from horses, cattle, and coyotes were
      nonreactive. Sera from cats and dogs that had trace IgG-antibody reactivity to
      nucleocapsid proteins were then tested for IgG-antibody reactivity to
      nucleocapsid proteins of prototypic hantaviruses. One cat had multiple cross
      reactivities with these hantaviruses, consistent with exposure to a hantavirus;
      however, epitope mapping studies did not support this conclusion. Reverse
      transcriptase polymerase chain reaction studies of blood clots or lung tissue
      from 2 animals that had weak reactivity to SNV failed to amplify any hantavirus
      sequence. CLINICAL IMPLICATIONS: Domestic animals, particularly dogs and cats, as
      well as coyotes do not appear to have a major role in the maintenance and
      transmission of SNV.

PMID- 9540867
TI  - Physical and serologic examinations of foals at 30 and 45 days of age for early
      diagnosis of Rhodococcus equi infection on endemically infected farms.
AB  - OBJECTIVE: To evaluate results of physical and serologic examinations of foals at
      30 and 45 days of age on 3 types of farms with various prevalences of clinical
      disease (endemic, sporadic, none) caused by Rhodococcus equi and to determine
      whether evaluations were helpful in early diagnosis and control of the disease.
      DESIGN: Prospective cohort study. ANIMALS: 144 foals at 30 and 45 days of age.
      PROCEDURE: During a 2-year period, 36 foals on farms at which R equi infection
      was endemic, 71 foals on farms at which the disease was sporadically detected,
      and 37 foals on farms without the disease were examined by means of auscultation
      of lungs, serum biochemical and hematologic analyses, and determination of
      antibody titers against R equi, using ELISA. Transtracheal aspirates were
      obtained from 14 of 32 foals that had clinical signs of disease and 7 of 41
      seropositive foals that did not have clinical signs of disease. RESULTS:
      Prevalences of respiratory tract disease and seropositive conversion rates for 45
      day-old foals on endemically and sporadically infected farms were significantly
      higher than on farms without the disease. Rhodococcus equi was isolated from
      tracheal aspirates of seropositive foals, even when clinical signs were not
      evident. CLINICAL IMPLICATIONS: Physical and serologic examinations of foals at
      30 and 45 days of age were useful for early diagnosis of R equi infection,
      especially for foals on farms at which the disease was endemic.

PMID- 9540868
TI  - Oocyte transfer in mares.
AB  - Oocytes were collected from dominant preovulatory follicles of donor mares 24
      hours after administration of human chorionic gonadotropin. Oocytes were
      incubated in vitro for 12 or 18 hours before transfer to recipient mares,
      representing maturation times after human chorionic gonadotropin administration
      of 36 and 42 hours, respectively. Pregnancy rates after transfer were 4 of 5 in
      the 36-hour group and 2 of 3 in the 42-hour group. The overall pregnancy rate
      achieved (6/8 mares) indicated that oocyte transfer may be useful clinically.

PMID- 9540869
TI  - Effects of an allicin-based product on cryptosporidiosis in neonatal calves.
AB  - OBJECTIVE: To evaluate effectiveness of an allicin-based product in neonatal
      calves inoculated with Cryptosporidium parvum. DESIGN: Randomized controlled
      study. ANIMALS: 43 neonatal calves. PROCEDURE: Calves were inoculated with 1.5 x
      10(8) or 7.5 x 10(5) C parvum oocysts within 2 days after birth. Calves were
      given an allicin-based product once after inoculation or daily for 7 days after
      inoculation or were not treated. Calves that developed diarrhea were treated by
      administration of the product. Fecal consistency scores and weight gains were
      statistically evaluated. RESULTS: Mean daily weight gain and severity of diarrhea
      in calves 4 to 21 days old were unaffected by prophylactic use of the product.
      However, intensive prophylactic administration may have delayed onset of C parvum
      induced diarrhea in calves inoculated with the lower dose of oocysts. CLINICAL
      IMPLICATIONS: Administration of an allicin-based product did not alter duration
      of C parvum-induced diarrhea or enhance weight gain in neonatal calves. However,
      intensive prophylactic administration of an allicin-based product may delay onset
      of diarrhea in calves exposed to C parvum oocysts.

PMID- 9540870
TI  - Clinical and laboratory assessment of hydration status of neonatal calves with
      diarrhea.
AB  - OBJECTIVE: To develop accurate, objective guidelines for assessing hydration
      status of neonatal calves with diarrhea. DESIGN: Prospective study. ANIMALS: 15
      male dairy calves 3 to 10 days old. PROCEDURE: Dehydration and diarrhea were
      induced by administration of diuretic agents (i.e., furosemide, spironolactone,
      hydrochlorothiazide) and sucrose solution. Linear regression was used to examine
      the relationship between potentially useful factors for evaluating hydration
      status (extent of enophthalmos; skin-tent duration on neck, thorax, and upper and
      lower eyelids; heart rate; mean central venous pressure; peripheral [extremity]
      and core [rectal] temperatures; core-peripheral [rectal-extremity] temperature
      difference; PCV; and hemoglobin and plasma protein concentrations) and degree of
      dehydration, as determined by change in body weight. RESULTS: Best predictors of
      degree of dehydration were extent of enophthalmos, skin elasticity on neck and
      thorax, and plasma protein concentration. CLINICAL IMPLICATIONS: These
      experimentally determined guidelines provide practitioners with a simple,
      inexpensive, and practical method for evaluating hydration status of neonatal
      calves with diarrhea.

PMID- 9540871
TI  - Effects of dietary vitamin E supplementation during late pregnancy on lamb
      mortality and ewe productivity.
AB  - OBJECTIVE: To determine the effect of feeding vitamin E to ewes during late
      pregnancy on lamb mortality and ewe productivity. DESIGN: Prospective study.
      ANIMALS: 1,302 mature Rambouillet and Targhee ewes. PROCEDURE: During a 3-year
      period, approximately 430 ewes/y were randomly allocated to 2 groups; supplement
      group ewes were fed additional vitamin E and control-group ewes were not.
      Beginning approximately 3 weeks before the first expected lambing date, ewes were
      fed 2.3 kg (5 lb) of alfalfa-grass hay/d and 0.23 kg (0.5 lb) of barley-based
      pellets/d with or without supplemental vitamin E. Pellets that were supplemented
      contained 1,450 mg of DL-alpha-tocopherol acetate/kg (658 mg/lb) of feed and
      provided an additional 330 IU of vitamin E/ewe/d. Selenium was incorporated into
      a trace mineral salt and fed free choice to all ewes throughout pregnancy.
      RESULTS: Supplemental vitamin E had no effect on ewe weight, body condition
      score, fertility, or prolificacy. In ewes that lambed in the early part of the
      lambing season, vitamin E supplementation significantly reduced lamb mortality,
      compared with no supplementation (12 vs 17%, respectively). Consequently,
      supplement-group ewes had significantly greater total body weight of lambs per
      ewe at the time of weaning, compared with control-group ewes. Differences were
      not observed between ewe groups in lamb mortality or total body weight of lambs
      per ewe at the time of weaning when ewes lambed during the late part of the
      lambing season. CLINICAL IMPLICATIONS: If ewes are fed additional vitamin E3
      weeks before parturition, those that lamb in the early part of the lambing season
      may have low lamb mortality and, thus, higher total body weight of lambs per ewe
      at the time of weaning.

PMID- 9540872
TI  - Assessment of spatial and temporal clustering of ampicillin- and tetracycline
      resistant strains of Pasteurella multocida and P haemolytica isolated from cattle
      in California.
AB  - OBJECTIVE: To determine whether ampicillin- and tetracycline-resistant strains of
      Pasteurella multocida and P haemolytica isolated from California cattle with
      pneumonia were spatially and temporally clustered and to compare overall
      estimates of percentages of these isolates resistant to these antimicrobials with
      estimates obtained on the basis of regional and temporal information. DESIGN:
      Epidemiologic study. SAMPLE POPULATION: Records of P multocida and P haemolytica
      isolates obtained from lung or tracheal wash samples collected from California
      cattle with pneumonia between July 1, 1991 and July 31, 1996. Only isolates
      obtained from samples submitted by dairies and calf ranches were used. PROCEDURE:
      Spatial clustering of ampicillin- and tetracycline-resistant isolates was
      assessed by use of nearest-neighbor and Cuzick and Edwards' analyses. Linear
      clustering along a north-south line was assessed by use of runs and maximum
      length of runs tests. Temporal clustering was assessed by use of scan tests.
      Spatial-temporal clustering was assessed by use of Barton's method. Regional
      estimates of percentages of P multocida and P haemolytica resistant to ampicillin
      or tetracycline were calculated. RESULTS: There was significant spatial
      clustering of resistant isolates and significant linear clustering along a north
      south line. Significant differences in regional estimates of percentages of
      antimicrobial-resistant isolates were found. CLINICAL IMPLICATIONS: Results
      support the hypothesis that antimicrobial-resistant organisms can be clustered at
      the local level and reinforce the need to establish regional estimates of
      percentages of bacterial isolates that will be susceptible to commonly used
      antimicrobials.

PMID- 9540873
TI  - Successful outpatient management of acute upper gastrointestinal hemorrhage: use
      of practice guidelines in a large patient series.
AB  - BACKGROUND: Acute upper gastrointestinal hemorrhage is a common reason for
      hospitalization. Clinical and endoscopic characteristics predict outcome. The aim
      of this study was to determine the characteristics and outcome of patients with
      acute upper gastrointestinal hemorrhage cared for without hospitalization.
      METHODS: One hundred seventy-six consecutive patients in a staff-model health
      maintenance organization were selected for outpatient care based on absolute
      endoscopic and non-absolute clinical criteria. Clinical and endoscopic
      characteristics, British national audit "risk scores," and rates of recurrent
      bleeding, hospitalization, and mortality were determined. RESULTS: Mean patient
      age (+/- SD) was 56.4 +/- 16.0 years, and 106 patients (60%) were men. One
      hundred one (57%) had endoscopy within 2 days of the onset of hemorrhage. The
      mean initial hemoglobin concentration was 11.7 +/- 2.3 mg/dL. Ninety-seven
      patients (55%) had a peptic ulcer, and 57 (32%) had a British risk score greater
      than 2. Hospitalization, recurrent bleeding, and mortality occurred in two (1%),
      one (1%), and zero (0%) patients, respectively, during 16.0 +/- 10.8 months of
      follow-up. CONCLUSIONS: Many patients with acute upper gastrointestinal
      hemorrhage can be safely treated as outpatients using endoscopic and clinical
      guidelines.

PMID- 9540874
TI  - Effects of bolus somatostatin in preventing pancreatitis after endoscopic
      pancreatography: results of a randomized study.
AB  - BACKGROUND: Pancreatitis is a potential problem in patients undergoing endoscopic
      retrograde cholangiopancreatography (ERCP). Natural somatostatin reduces
      pancreatic secretion and has been administered in acute pancreatitis. To
      establish whether an injection of a single "bolus" of natural somatostatin is
      useful in preventing pancreatic reactions after endoscopic pancreatography, a
      randomized study was carried out in 160 patients undergoing pancreatography,
      associated or not, with endoscopic sphincterotomy. METHODS: Pancreatitis was
      considered to be present when there was the simultaneous appearance of serum
      amylase above 600 IU/mL and serum lipase above 200 IU, upper abdominal pain with
      tenderness, nausea and/or vomiting, and associated ileus, not completely resolved
      within 18 hours after the procedure and prolonging hospital stay. RESULTS: The
      incidence of pancreatitis (10% vs. 2.5%, p < 0.05) was higher in the placebo
      group than in the somatostatin-treated group. The difference in frequency of
      pancreatitis was statistically significant (18% vs 0%, p < 0.05) in the ERCP plus
      sphincterotomy subgroup but not significant (6% versus 4%) in the ERCP subgroup.
      CONCLUSIONS: These results suggest that the administration of a single bolus
      injection of natural somatostatin just before cannulation of the papilla may be
      useful in preventing pancreatitis. This procedure is useful in patients
      undergoing sphincterotomy. Further studies should be performed to determine
      whether this drug is useful in cases in which cannulation of the papilla is
      difficult or when therapeutic procedures require prolonged and/or aggressive
      manipulation of the papilla.

PMID- 9540875
TI  - Injection sclerotherapy for variceal bleeding in patients with hepatocellular
      carcinoma: cyanoacrylate versus sodium tetradecyl sulphate.
AB  - BACKGROUND: Patients with hepatocellular carcinoma complicated by variceal
      bleeding have a very limited life span. Recurrent bleeding after endoscopic
      injection sclerotherapy is common. Our aim was to compare the efficacy of
      endoscopic injection of cyanoacrylate versus sodium tetradecyl sulphate in the
      control of variceal bleeding in patients with hepatocellular carcinoma. METHODS:
      Patients known to be suffering from inoperable hepatocellular carcinoma who
      presented with upper gastrointestinal bleeding underwent endoscopy within 24
      hours of admission. After bleeding from esophageal varices was confirmed, they
      were randomized to receive endoscopic injections of either cyanoacrylate (1:1
      mixture with Lipoidol) or sodium tetradecyl sulphate (1.5%). Injection were given
      intravariceally into each visible column for up to four injections for
      cyanoacrylate and up to 30 mL for sodium tetradecyl sulphate. RESULTS: A total of
      50 patients were recruited for this study with 25 cases randomized to each
      endoscopic treatment group. Control of acute bleeding failed in four patients
      (16%) in both treatment groups, and two patients in each group died during the
      index episode of bleeding. Six patients (24%) in the cyanoacrylate group and four
      patients (16%) in the sodium tetradecyl sulphate group developed recurrent
      bleeding during their hospital stay (p = 0.48). Recurrent bleeding within 30 days
      after the index episode of bleeding was documented in seven patients (28%) who
      received cyanoacrylate injection and five patients (20%) who received sodium
      tetradecyl sulphate injection (p = 0.51). Median survival in the cyanoacrylate
      group was 16 days (range 1 to 485 days) and that of the sodium tetradecyl
      sulphate group was 13 days (range 1 to 407 days). There was no difference in
      cumulative survival between the two groups as analyzed by the Kaplan-Meier
      method. Patients with portal vein thrombosis had a higher risk of recurrent
      hemorrhage. Patients with Child's C liver disease had a significantly higher
      mortality. CONCLUSIONS: Cyanoacrylate did not improve the outcome of
      hepatocellular carcinoma patients with variceal hemorrhage.

PMID- 9540876
TI  - Endoscopic pancreatic sphincterotomy: indications, outcome, and a safe stentless
      technique.
AB  - BACKGROUND: Endoscopic pancreatic sphincterotomy is less widely practiced than
      biliary sphincterotomy, in part because of the lack of firm data regarding its
      indications and safety. In addition, recent reports of ductal and parenchymal
      changes occurring after pancreatic stenting raise concerns about the standard
      practice of stent placement at the time of pancreatic sphincterotomy. We report
      our experience with pancreatic sphincterotomy and describe the use of a technique
      involving overnight nasopancreatic drainage rather than stenting. METHODS: We
      reviewed the records of the 164 pancreatic sphincterotomies performed on 160
      patients at our institution between January 1, 1991, and October 1, 1996,
      comparing procedures done with overnight nasopancreatic catheter placement with
      those done with stenting or no drainage. We also examined the long-term clinical
      outcome of patients after pancreatic sphincterotomy. RESULTS: Of the 164
      sphincterotomies, 98 were done with overnight nasopancreatic drainage, 50 with
      stent placement, and 16 with no drainage. Complications (all pancreatitis) were
      significantly more frequent in the group with no drainage (12.5%) as compared
      with those with drainage (0.7%); p < 0.003. Nasopancreatic drainage was as safe
      as stent placement, with no complications after 98 procedures. Pancreatic
      sphincterotomy was effective when used as primary therapy, with 64% of patients
      so treated experiencing complete and long-lasting resolution of symptoms after
      the procedure. CONCLUSIONS: Pancreatic sphincterotomy is safe and effective,
      although pancreatic drainage is required to reduce the incidence of pancreatitis.
      Overnight nasopancreatic drainage is the method of choice, as it carries as low a
      complication rate as stent placement, but without the need for a repeat
      procedure, and presumably without the risk of ductal and parenchymal damage.

PMID- 9540877
TI  - Accuracy of CLOtest after Helicobacter pylori therapy.
AB  - BACKGROUND: The accuracy of rapid urease testing after Helicobacter pylori
      therapy has not been widely studied and might be diminished because of decreased
      numbers of organisms. We assessed CLOtest results after therapy in two
      randomized, double-blind trials. METHODS: A total of 233 patients (in two
      separate studies) with true-positive baseline CLOtests (by histology or culture)
      received 2 weeks of omeprazole/amoxicillin, omeprazole, or amoxicillin. In study
      1, patients received an additional 2 weeks of omeprazole therapy (20 mg/day) or
      placebo; no additional therapy was given in study 2. Endoscopy was repeated 4
      weeks after completion of therapy in both studies. A diagnosis of cure required
      at least two negative endoscopic biopsy tests (histology, culture, CLOtest) and
      no positive tests. RESULTS: After therapy, 178 patients (76%) remained positive
      for H. pylori by histology and/or culture for both studies combined. Post-therapy
      CLOtest sensitivity was 86% and specificity was 95%. Sensitivity was poorer in
      patients after dual therapy than after monotherapy in both study 1 (68% vs. 89%;
      p = 0.03) and study 2 (75% vs. 94%; p = 0.03). CONCLUSIONS: CLOtest sensitivity
      after therapy was lower than expected in our large group of patients with
      baseline true-positive CLOtests. In addition, sensitivity was lower after the use
      of more effective therapy (i.e., dual therapy as compared with monotherapy).
      Although most patients with unsuccessful treatment will be identified with the
      CLOtest alone, a negative result should not be taken as diagnostic of
      eradication.

PMID- 9540878
TI  - White ball appearance in endoscopic ligation of bleeding esophageal varices.
AB  - BACKGROUND: Endoscopic variceal ligation is useful in the control of bleeding
      from esophageal varices. However, confirmation of ligation precisely at the site
      of bleeding is usually difficult when treating massive variceal bleeding.
      Characteristic endoscopic findings that appeared when ligation was performed at
      the site of bleeding are reported in this article. METHODS: Emergency endoscopic
      variceal ligation was performed in 14 patients with active bleeding from
      esophageal varices. Endoscopic findings after variceal ligation at the site of
      bleeding were compared with those at sites without bleeding. RESULTS: Active
      bleeding ceased just after endoscopic ligation at the site of bleeding in all
      patients. After ligation of the bleeding site of the varix, an unusual white
      colored ball-like appearance (white ball appearance) was observed in all
      patients. This finding was markedly different from the purple-colored ball-like
      appearance that is usually observed after ligation of a varix at a site without
      bleeding. CONCLUSIONS: White ball appearance was a characteristic finding that
      appeared after ligation of a varix at the site of bleeding. This finding may be
      useful in the confirmation of successful ligation of a varix at its bleeding
      site.

PMID- 9540879
TI  - India ink tattooing in the esophagus.
AB  - BACKGROUND: Precise endoscopic measurement of esophageal landmarks is difficult
      and inaccurate because of the ability of the esophagus to lengthen and
      foreshorten. METHODS: Nineteen patients enrolled to date in a study of Barrett's
      esophagus had an India ink tattoo placed at the most proximal level of the
      squamocolumnar junction and were examined endoscopically at 3, 9, 15, 24, and 36
      months. RESULTS: Eighteen of nineteen patients (94.7%) were judged to have a good
      to excellent tattoo persistence at 3 months. One of the 19 patients (5.3%) had
      poor tattoo persistence and was retattooed at the 3-month interval. Eventually,
      15 of the 15 patients (100%) who remained in the study had a good or excellent
      tattoo persistence at 36 months. There were no complications related to India ink
      tattooing including chest pain, bleeding, or perforation. At follow-up endoscopy,
      no ulcers, inflammation, break in the mucosa, or pain were noted. CONCLUSION:
      India ink tattooing in the esophagus is safe and persistent and may be used as an
      effective method for longitudinal follow-up of lesions in the esophagus.

PMID- 9540880
TI  - Endoscopic intervention for biliary leaks after laparoscopic cholecystectomy: a
      multicenter review.
AB  - BACKGROUND: Endoscopic therapy of biliary tract leaks was uncommon before
      laparoscopic cholecystectomy. Studies have demonstrated the efficacy of
      endoscopic drainage by endoscopic sphincterotomy or stent placement. Various
      endoscopic therapeutic modalities and long-term follow-up of this problem were
      studied. METHODS: Members of the Midwest Pancreaticobiliary Group reviewed all
      patients referred for endoscopic therapy of biliary leaks after laparoscopic
      cholecystectomy from 1990 to 1994. Long-term follow-up was by direct patient
      contact. RESULTS: Fifty patients were referred for endoscopic therapy of biliary
      leaks. Abdominal pain was present in 94%. The mean time from laparoscopic
      cholecystectomy to referral was 6.9 days. Therapy consisted of sphincterotomy
      only in 6 patients, stent only in 13, and sphincterotomy with stent in 31.
      Biliary leaks were healed in 44 patients at a mean of 5.4 weeks. A second or
      third endoscopic procedure was necessary to achieve healing in five patients. Two
      stent-related complications were noted. Percutaneous or surgical drainage of
      biliary fluid collections was required in 16 patients. The mean hospital stay for
      treatment of the leak was 11.1 days after endoscopic therapy. On follow-up (mean
      17.5 months), all patients were well except two with mild abdominal discomfort.
      CONCLUSIONS: Endoscopic sphincterotomy, stent placement, or sphincterotomy with
      stent are effective in healing biliary leaks after laparoscopic cholecystectomy.
      Despite prolonged treatment for the leak, patients did well on long-term follow
      up.

PMID- 9540881
TI  - Palliation of malignant gastric outlet obstruction using an endoscopically placed
      Wallstent.
AB  - BACKGROUND: Treatment options for malignant gastric outlet obstruction are
      limited. Surgical gastrojejunostomy, commonly performed, has significant
      morbidity and mortality. METHODS: Over 2 years, we prospectively studied the
      safety, feasibility, and outcomes for use of a newly designed expandable metal
      stent (Wallstent Enteral; Schneider, Minneapolis, Minn.) to treat malignant
      gastric outlet obstruction. Stents 16 to 22 mm in diameter and 60 to 90 mm in
      length were deployed directly through the endoscope. RESULTS: Twelve patients
      (ten women, two men; mean age 59.7 years) underwent stenting. Thereafter, six
      patients were able to eat a regular diet; three could eat pureed food. In three
      patients, the procedure was unsuccessful because of multiple obstructions not
      recognized before stenting (one) and stents deployed too proximally (one) or too
      distally (one). CONCLUSIONS: Placement of a newly designed stent through the
      endoscope is safe and effective palliation for various types of malignant gastric
      outlet obstruction and significantly improves many aspects of patient quality of
      life.

PMID- 9540882
TI  - Expandable metallic prostheses for malignant obstructions of gastric outlet and
      proximal small bowel.
AB  - BACKGROUND: Data are limited on use of expandable metal stents for treatment of
      malignant gastric outlet obstruction. Accordingly, we report our experience using
      these stents to palliate malignant obstructions of the gastric outlet, duodenum,
      and proximal jejunum. METHODS: Eight patients with malignant strictures causing
      gastric obstruction underwent endoscopy with fluoroscopic guidance to delineate
      tumor borders and length followed by expandable metallic prosthesis placement
      (Wallstent, Z-Stent, Ultraflex, and Endocoil). RESULTS: Symptoms were relieved in
      seven patients, five of whom had previous surgeries (Whipple, Billroth II,
      esophagojejunostomy, and gastrojejunostomy) for malignancy. One patient underwent
      surgical resection of a presumed malignant stricture containing a previously
      placed Wallstent after a 45-pound weight gain. CONCLUSIONS: Expandable metallic
      prostheses placed in patients with malignant obstruction of the gastric outlet,
      duodenum, or proximal jejunum, before or after surgery, effectively palliate
      obstructive symptoms and may also serve to improve nutrition.

PMID- 9540883
TI  - Expandable metal stents for the treatment of colonic obstruction: techniques and
      outcomes.
AB  - BACKGROUND: Acute left-sided colonic obstruction is a surgical emergency whose
      management is controversial. Because experience using expandable metal stents for
      relief of this type of obstruction is limited, we evaluated their effectiveness,
      feasibility, safety, and outcome. METHODS: Twenty-five patients with acute
      colorectal obstruction underwent placement of various metal stents under
      fluoroscopic and endoscopic guidance. On an intent-to-treat basis, stents were
      placed for decompression before one-stage surgical resection in 10 patients and
      palliatively in 15 patients. Two preoperative patients had unresectable malignant
      disease, and stents were left for palliation resulting in 17 palliative and 10
      preoperative patients for analysis. RESULTS: Stent placement was technically
      successful in 94% of patients. Overall effectiveness in relieving obstruction was
      85% (palliative 82%, preoperative 90%). In the palliative group, stent duration
      ranged from 2 to 64 weeks (mean 17.3 weeks). Major complications occurred in 7
      patients (30%). CONCLUSIONS: Expandable metal stents are a feasible, effective
      adjunct and alternative to surgery for acute colorectal obstruction.

PMID- 9540884
TI  - Self-expanding metal stents in the palliation of small bowel stenosis secondary
      to recurrent gastric cancer.

PMID- 9540885
TI  - Acute hemorrhagic gastropathy with multiple shallow ulcers and duodenitis caused
      by a laboratory infection of Helicobacter pylori.

PMID- 9540886
TI  - Adenosquamous carcinoma of the esophagus after endoscopic variceal sclerotherapy:
      a case report and review of the literature.

PMID- 9540887
TI  - Bleeding downhill esophageal varices: a complication of upper extremity
      hemodialysis access.

PMID- 9540888
TI  - Duplication cyst of the pancreatic duct presenting as pancreatitis.

PMID- 9540889
TI  - Melanosis coli associated with ingestion of bamboo leaf extract.

PMID- 9540890
TI  - Endoscopic polypectomy of an unusually long polypoid colorectal cavernous
      hemangioma.

PMID- 9540891
TI  - Treatment of pancreatic duct stones with the use of endoscopic balloon sphincter
      dilation.

PMID- 9540892
TI  - Outpatient management of upper gastrointestinal bleeding: Has the time finally
      arrived?

PMID- 9540893
TI  - Should chromoscopy be part of the "proficient" endoscopist's armamentarium?

PMID- 9540894
TI  - Endosonography-guided, fine-needle biopsy of indurated pancreatic lesions using
      an automated biopsy device.

PMID- 9540895
TI  - Three-dimensional endosonography for staging of rectal cancer.

PMID- 9540896
TI  - Management of esophageal perforation after therapeutic upper gastrointestinal
      endoscopy.

PMID- 9540897
TI  - The impact of mass screening on gastric cancer mortality in Japan.

PMID- 9540898
TI  - Laparoscopy in chronic renal failure.

PMID- 9540899
TI  - Contrast agents for endoscopic ultrasound.

PMID- 9540900
TI  - Endoscopic ultrasound of gastric inflammatory fibroid polyps.

PMID- 9540901
TI  - 1998 SCVIR Gary J. Becker Young Investigator Award. Endovascular repair of
      arterial pseudoaneurysms with use of a perfusion balloon catheter.
AB  - PURPOSE: Pseudoaneurysms represent contained disruption of the arterial wall.
      Iatrogenic pseudoaneurysms frequently complicate complex endovascular procedures.
      With use of an animal model, the authors attempted to determine the safety and
      efficacy of using a perfusion balloon catheter (PBC) to thrombose surgically
      created pseudoaneurysms. MATERIALS AND METHODS: An in vitro system measured
      maximum flow volume through a 5-F PBC. Pseudoaneurysms were created in domestic
      swine with use of a jugular vein patch anastomosed to a femoral arteriotomy. The
      PBC was inflated across the pseudoaneurysm neck for 30-minute intervals until
      thrombosis was confirmed by ultrasound. Completion arteriography was performed to
      evaluate for vascular complications. RESULTS: Maximum flow through the PBC was
      62.6 mL/min measured at a constant pressure gradient of 120 mm Hg. Five
      pseudoaneurysms were created in four animals. The PBC completely thrombosed all
      five lesions. The mean treatment duration was 129 minutes (+/- 39 minutes SD). No
      native arterial injury, in situ thrombus, or distal embolization occurred.
      Partial recanalization of three of the five treated pseudoaneurysms was
      identified on follow-up arteriography and gross sectioning (n = 2 and n = 1,
      respectively). CONCLUSION: The PBC safely and effectively thrombosed surgically
      created pseudoaneurysms. Partial recanalization of treated pseudoaneurysms was
      demonstrated. Clinical trials are warranted.

PMID- 9540902
TI  - The role of radiation therapy in the management of vascular restenosis. Part I.
      Biologic basis.

PMID- 9540903
TI  - Current status of percutaneous mechanical thrombectomy. Part III. Present and
      future applications.

PMID- 9540904
TI  - Comparison of conventional angioplasty with the Palmaz stent in the treatment of
      abdominal aortic stenoses from the STAR registry. SCVIR Transluminal Angioplasty
      and Revascularization.
AB  - PURPOSE: To retrospectively compare the safety and short-term efficacy of
      conventional percutaneous transluminal angioplasty (PTA) and PTA with the Palmaz
      balloon-expandable intravascular stent for the treatment of infrarenal abdominal
      aortic atherosclerotic stenoses. PATIENTS AND METHODS: The records of 25 patients
      with infrarenal aortic stenoses treated by means of percutaneous techniques were
      retrieved from the SCVIR Transluminal Angioplasty and Revascularization (STAR)
      Registry and analyzed. Thirteen patients were treated with PTA alone and 12 were
      treated with the Palmaz intravascular stent. RESULTS: Technical success was
      achieved in 92% of patients treated with PTA alone and in 100% of those treated
      with the Palmaz stent. Significant improvements in lesion morphology,
      hemodynamics, clinical status, and ankle arm indexes were shown in both groups.
      There was no statistically significant difference in percent stenosis reduction,
      decrease in trans-stenotic gradient, or initial clinical outcome between the
      group treated by means of PTA and the group treated by means of PTA with the
      Palmaz stent. CONCLUSIONS: PTA and intravascular stent placement of
      atherosclerotic stenoses involving the infrarenal aorta are both safe and
      efficacious therapeutic modalities. At present, it does not appear that primary
      stent placement confers any short-term benefits over technically successful PTA
      in aortic stenoses.

PMID- 9540905
TI  - Complications and technical limitations of hepatic arterial infusion catheter
      placement for chemotherapy.
AB  - PURPOSE: To determine the rate of complications associated with hepatic arterial
      infusion (HAI) catheter placement, as well as technical success related to liver
      perfusion. MATERIALS AND METHODS: The authors reviewed 44 patients who underwent
      106 HAI catheter placements, including 15 men and 29 women with an average age of
      55 years (range, 32-82 years). One to nine placements were performed per patient
      with 61 (58%) via the left brachial artery, 40 (38%) via the right femoral
      artery, and five (4%) via the left femoral artery. Chemoinfusion lasted 4 days,
      with initial catheter placement assessed on technetium-99m macroaggregated
      albumin (MAA) perfusion scans, as well as daily abdominal radiographs. RESULTS:
      One hundred attempted hepatic arterial catheter placements were completed. Liver
      perfusion was global in 66 (66%) cases, in the right lobe only in 28 (28%) cases,
      and in the left lobe only in six (6%) cases. Eight (8%) had gastrointestinal (GI)
      tract perfusion; this was eliminated in seven cases (7%) after catheter
      repositioning. Forty-six (43%) placement attempts required embolization of 62 GI
      vessels to preclude GI chemoinfusion. Complications included one cerebrovascular
      accident (related to removal of a left brachial catheter), eight brachial artery
      thromboses (four that required emergent thrombectomy), six hepatic arterial
      dissections, four hepatic arterial thromboses, and four catheter malfunctions.
      CONCLUSIONS: HAI catheter placement via the left brachial artery has increased
      complications. Nearly one-half of placements required embolization of GI vessels
      to preclude GI perfusion. Global perfusion is possible in two-thirds of cases.

PMID- 9540906
TI  - Combined direct puncture of the PTFE graft and contralateral snare loop technique
      for catheterization of an occluded femoropopliteal graft.

PMID- 9540907
TI  - Endoluminal repair of an internal carotid artery pseudoaneurysm.

PMID- 9540908
TI  - Anchoring coil embolization in a high-flow arterial model: a pilot study.
AB  - PURPOSE: To devise and test an occluding coil anchoring system to improve the
      safety of coil embolization. MATERIALS AND METHODS: The anchoring system was
      attached to Gianturco embolization coils and investigated in 15 pigs. In the
      short-term studies, one 0.035-inch anchored coil (15-18 cm in length and 7-10 mm
      in diameter) was placed in the infrarenal portion of the abdominal aorta in each
      of 12 pigs with use of an 8-F catheter from the carotid approach. Aortography was
      performed before and up to 4 hours after coil placement. In the long-term
      studies, 0.028-inch anchored coils (8 cm in length and 5 mm in diameter) were
      placed in the left femoral and the right carotid arteries in each of three pigs
      with use of a 6-F catheter positioned from the right femoral approach. One week
      later, the animals were evaluated angiographically for coil migration and
      vascular occlusion. RESULTS: Radiographically, the coils created a compact
      conglomerate on placement in all but one of the animals. No coil migration was
      noted during follow-up. Necropsy confirmed compact arrangement of the coils
      within the vessels and revealed effective anchoring of the device in all cases.
      CONCLUSIONS: The anchoring coil has proved effective in making coil embolization
      safer, especially in a high-flow arterial model.

PMID- 9540909
TI  - Renal angiomyolipoma: embolotherapy with a mixture of alcohol and iodized oil.
AB  - PURPOSE: To evaluate the efficacy of superselective embolotherapy of renal
      angiomyolipomas with a 1:3 mixture of iodized oil and absolute ethanol as embolic
      material. MATERIALS AND METHODS: Fifteen patients with 21 symptomatic renal
      angiomyolipomas were treated with embolization. The sizes of tumors ranged from 6
      cm to 15 cm (mean, 8.6 cm). Six of 15 patients were diagnosed with tuberous
      sclerosis. The diagnoses of renal angiomyolipoma were made from characteristic
      computed tomographic findings. All angiomyolipomas were successfully embolized
      with a 1:3 mixture of iodized oil and absolute ethanol (2-20 mL; mean, 8.5 mL).
      Patients were followed up from 5 months to 8 years (mean, 35.6 months). The
      efficacy of embolotherapy was evaluated by symptom-free period, immediate and
      late complications, and follow-up imaging findings, including changes in tumor
      size. RESULTS: Thirteen patients showed no symptom recurrence during follow-up
      periods from 3 months to 8 years. Two patients with incomplete embolization
      required repeated embolization because of the recurrence of perinephric hematoma
      or other symptoms. Twelve patients experienced mild postembolization syndrome,
      which subsided with conservative management. A moderate amount of pleural
      effusion developed in one patient and was managed with percutaneous drainage. No
      patients developed any severe late complications, hypertension, or renal failure.
      During the follow-up period, 12 tumors decreased in size, whereas there was no
      change in eight tumors, and in one tumor imaging follow-up was not available.
      CONCLUSION: Embolization with a 1:3 mixture of iodized oil and absolute ethanol
      is an effective method of treatment in renal angiomyolipoma with favorable
      results. But incomplete embolization of angiomyolipoma results in a high
      incidence of recurrent symptoms due to bleeding.

PMID- 9540910
TI  - Bone metastases from renal cell carcinoma: preoperative embolization.
AB  - PURPOSE: To assess the effect of preoperative embolization on blood loss during
      surgical repair of bone metastases from renal cell carcinoma and provide long
      term follow-up. PATIENTS AND METHODS: Sixteen patients with bone metastases
      underwent preoperative embolization. Polyvinyl alcohol (PVA) particles were used
      for 13 patients (three with additional coils), and coils alone were used in three
      patients. Surgery was performed within 24 hours in four patients, and within 36
      120 hours in 12 patients. Bone healing was evaluated radiographically and
      clinically. RESULTS: Tumor stain was obliterated by more than 70% in 12 patients,
      51%-69% in two patients, and less than 50% in two patients. Estimated blood loss
      (EBL) during surgery ranged from 100 to 1,000 mL (mean, 533 mL). EBL was
      significantly less when more than 70% of the tumor stain was obliterated (460 mL
      vs 750 mL; P < .01 ). There were no significant differences in EBL between the
      patients who underwent surgery within 24 hours (575 mL) and those who underwent
      surgery more than 36 hours after embolization (402 mL) when PVA was used. Bone
      healing was achieved in all patients. Survival ranged from 3 to 56 months
      (median, 12 months). CONCLUSION: Preoperative embolization reduced intraoperative
      blood loss without adverse effects on healing. Best results were achieved when
      more than 70% of the tumor stain was obliterated.

PMID- 9540911
TI  - Bilateral adrenal hemorrhage resulting in acute adrenal insufficiency as an
      unusual complication of hepatic arterial chemoembolization.

PMID- 9540912
TI  - Long-term follow-up after TIPS: use of Doppler velocity criteria for detecting
      elevation of the portosystemic gradient.
AB  - PURPOSE: To evaluate the performance of Doppler ultrasound as a screening test
      for detecting elevated portosystemic gradients in failing transjugular
      intrahepatic portosystemic shunts (TIPS). MATERIALS AND METHODS: Twenty-seven of
      61 patients who underwent TIPS creation between November 1991 and March 1996 were
      studied. At routine intervals, angle-corrected velocity measurements of portal
      venous and intrashunt blood flow (at the portal venous, middle, and hepatic
      venous levels of the shunt) were obtained. These were compared with portal
      hemodynamics for diagnostic accuracy in predicting clinically significant
      elevation of the portosystemic gradient. Venographic and manometric correlations
      were obtained on all patients available for follow-up and were not limited to
      those with symptoms or "abnormal" Doppler studies. Receiver-operating
      characteristic (ROC) curves were done. Linear regression was done to study
      correlation of shunt velocities with portal pressure, and logistic regression was
      done to predict shunt stenosis with use of shunt velocities. RESULTS: The most
      accurate location for shunt velocity measurement was the main portal vein, but
      this had an area under the ROC curve of only 0.70. Accuracy of any velocity
      threshold (including maximum shunt velocity) was no greater than 70%. Maximum
      shunt velocity of less than 60 cm/sec was 93% specific for detecting shunt
      restenosis, but only 25% sensitive, for an overall accuracy of 64%. High
      sensitivity (90%) could only be achieved with poor specificity (< 33%). Linear
      regression revealed poor correlation between shunt or portal vein velocity
      measurements and portal pressure (/r/ < 0.23 for all). CONCLUSIONS: Intrashunt
      and portal venous Doppler velocities alone do not accurately predict elevation of
      the portosystemic gradient on long-term follow-up after TIPS.

PMID- 9540913
TI  - Technical considerations in covering and deploying a Wallstent endoprosthesis for
      the salvage of a failing transjugular intrahepatic portosystemic shunt.

PMID- 9540914
TI  - In vitro model for the evaluation of inferior vena cava filters: effect of
      experimental parameters on thrombus-capturing efficacy of the Vena Tech-LGM
      filter.
AB  - PURPOSE: To determine the experimental parameters in an in vitro model that
      influence the thrombus-capturing efficacy of the Vena Tech-LGM filter. MATERIALS
      AND METHODS: The Vena Tech-LGM filter was evaluated in an in vitro model of the
      vena cava with a computer-controlled flow system with a total of 5,200 thrombi.
      The influences of the following experimental parameters on the capture rate were
      analyzed with a multiple logistic regression model: type of testing (single,
      double, and multiple shot testing), thrombus diameter and length, IVC diameter
      and orientation, flow quality and quantity, flow velocity, and the length of the
      prepositioned thrombus. RESULTS: A significant influence on the capture rate
      could be demonstrated for the type of testing, the thrombus diameter and length,
      the IVC diameter, and with double shot testing for the length of the
      prepositioned thrombus and the IVC orientation. The flow quality and the peak
      velocity were not significant. Based on these results, a protocol for in vitro
      testing of IVC filters was designed. CONCLUSIONS: Experimental parameters
      influence the thrombus-capturing efficacy of the Vena Tech-LGM filter and should
      be taken into account when in vitro testing is performed.

PMID- 9540915
TI  - Modification of arterial and portal hemodynamics after injection of iodized oils
      and different emulsions of iodized oils in the hepatic artery: an experimental
      study.
AB  - PURPOSE: A strong embolic effect of iodized oil/drug mixtures injected in the
      hepatic artery appeared to be an efficient way of prolonging the contact time
      between drugs and tumor tissue. Therefore, the authors evaluated arterial and
      portal embolic effects after hepatic intra-arterial injection of iodized oils and
      various emulsions of iodized oil. MATERIALS AND METHODS: Twenty-five pigs were
      monitored for the Doppler resistance index (DRI) in the hepatic artery and wedge
      hepatic vein pressure (WHVP) during 1 hour after injection of pure iodized oil,
      ultra-fluid or fluid, and four different emulsions of iodized oil ultra-fluid,
      into the hepatic artery. RESULTS: Mean area under the curve (AUC) values of DRI
      increases varied from 20.3 to 24.2 after injection of pure iodized oils or water
      in-oil emulsions, and were 13.2 for large-droplet oil-in-water emulsion and 8.2
      for small-droplet oil-in-water emulsion. Mean AUC values of WHVP increases varied
      from 151.6 to 195.6 after injection of pure iodized oils or water-in-oil
      emulsions, and were 105.5 for large-droplet oil-in-water emulsion and 8.5 for
      small-droplet oil-in-water emulsion. There was a significant difference in DRI
      and WHVP modifications between small-droplet oil-in-water emulsions and all other
      products (P = .001), between the two oil-in-water emulsions and the two water-in
      oil emulsions (P = .004), and between the two oil-in-water emulsions and pure
      iodized oils (P = .002). CONCLUSION: After hepatic intra-arterial injection,
      water-in-oil emulsions and pure iodized oils provided a stronger embolic effect
      than oil-in-water emulsion, both in the hepatic artery and in the portal vein.

PMID- 9540916
TI  - Halothane-induced intrahepatic portovenous shunting reduces hepatic microvascular
      sinusoidal perfusion during contrast angiographic procedures.
AB  - PURPOSE: Reduced intrahepatic perfusion that occurs during contrast angiography
      performed after administration of halothane anesthesia is thought to result from
      halothane-induced systemic hemodynamic alterations, such as reduced splanchnic
      blood flow, rather than intrahepatic microvascular alterations. The authors
      postulate that intrinsic hepatic effects caused by inhalational anesthetic agents
      rather than contrast materials, further reduce liver perfusion. MATERIALS AND
      METHODS: With use of dynamic video microscopy, intrahepatic microvascular flow
      rates and patterns, hepatic cord/sinusoidal diameters, portal venous pressure
      changes, and quantitative and qualitative Kupffer cell phagocytic activity were
      continuously recorded in isolated perfused rat livers before and during exposure
      to 1.5% halothane in O2/CO2, with and without the addition of iothalamate
      meglumine. RESULTS: Exposure of livers to halothane resulted in intrahepatic
      portovenous shunting secondary to obstruction to sinusoidal outflow, diminished
      sinusoidal perfusion, and a mean elevation in terminal portal venous pressure of
      12.8 mm Hg. Kupffer cell phagocytic activity was reduced even when normalized for
      flow within sinusoids. None of these changes were attributed to use of contrast
      material. CONCLUSIONS: Alterations in hepatic blood flow during exposure to
      halothane result, in part, from increased intrinsic hepatic vascular resistance,
      sinusoidal outflow obstruction, and portovenous shunting, and not only from
      systemic hemodynamic changes. Iothalamate meglumine produced no microvascular
      alterations.

PMID- 9540917
TI  - Replacement of failing tunneled hemodialysis catheters through pre-existing
      subcutaneous tunnels: a comparison of catheter function and infection rates for
      de novo placements and over-the-wire exchanges.
AB  - PURPOSE: Tunneled hemodialysis catheter dysfunction often occurs from fibrin
      sheath formation. As a way to preserve existing catheter venous access sites, the
      authors evaluated over-the-wire exchange of catheters through pre-existing
      subcutaneous tunnels as an alternative to catheter removal and de novo catheter
      replacement. PATIENTS AND METHODS: One hundred nineteen catheters were placed in
      68 patients. Seventy-seven catheters were placed de novo and 42 catheters were
      placed through the pre-existing subcutaneous tunnels of failing catheters.
      Technical success, short-term complications, infection rates, and functional
      catheter longevity were evaluated. RESULTS: Technical success for catheter
      exchange was 93%. Infection rates were comparable to those of de novo catheter
      placement: 0.15 and 0.11 infections per 100 catheter days for de novo and
      exchanged catheters, respectively. Catheter duration of function was not
      significantly different for de novo versus exchanged catheters: 63% and 51% at 3
      months, 51% and 37% at 6 months, and 35% and 30% at 12 months, respectively.
      CONCLUSIONS: Over-the-wire exchange of tunneled hemodialysis catheters is safe
      and easily performed. It causes no increase in infectious complications and
      provides similar catheter longevity to de novo catheter placement. The procedure
      is an important option for prolonging tunneled hemodialysis catheter access
      sites.

PMID- 9540918
TI  - Hemodialysis graft thrombectomy complicated by Fogarty catheter-induced arterial
      pseudoaneurysm.

PMID- 9540919
TI  - US-guided puncture of the internal jugular vein: complications and anatomic
      considerations.
AB  - PURPOSE: To examine success and complication rates for ultrasound (US)-guided
      cannulation of the internal jugular vein (IJV) in comparison with blind
      techniques and to present the variations in anatomy of the IJV. MATERIALS AND
      METHODS: Data were prospectively collected for 869 cases of sonographically
      guided cannulation of the IJV. In all cases, the side of the puncture, procedural
      success or failure, and any immediate complications were recorded. In 764 (88%)
      cases, the number of passes required and whether a single- or double-wall
      puncture was used were recorded. In 690 (79%) cases, IJV diameter and depth were
      recorded, while its relationship to the common carotid artery (CCA) was noted in
      659 (76%) cases. RESULTS: Cannulation was successful in 868 (99.9%) cases.
      Complications occurred in 20 (2.3%) cases. Eighty-seven percent of cannulations
      were achieved with one pass and 83% with a single-wall puncture. Success at first
      pass was significantly correlated with right-sided puncture and the diameter of
      the IJV. In 5.5% of cases, the IJV lay medial to the CCA, making successful
      cannulation with use of the landmark technique unlikely. CONCLUSIONS: US-guided
      cannulation of the IJV is superior to blind techniques, increasing the success
      rate and incidence of first pass cannulation and reducing the incidence of
      complications.

PMID- 9540920
TI  - Congenital anomalies of the inferior vena cava and left renal vein: evaluation
      with spiral CT.
AB  - PURPOSE: To determine with spiral computed tomography (CT) the incidence and
      caval location of left renal vein (LRV) variants that may affect inferior vena
      cava (IVC) filter placement, spermatic vein embolization, and adrenal or renal
      venous sampling. MATERIALS AND METHODS: Contrast material-enhanced spiral CT
      scans of 1,014 patients were evaluated for the incidence and configuration of LRV
      variants and for the distribution of the entrances of these veins into the IVC.
      RESULTS: In this series, variants detected were as follows: one azygos
      continuation of the IVC (0.1%), three bilateral IVCs (0.3%), and 102 LRV variants
      (10%) including 38 retroaortic renal veins (3.7%) and 64 circumaortic venous
      rings (6.3%). In the retroaortic renal vein group, the distance between the
      entrance of the LRV into the IVC and the confluence of the iliac veins was +62.5
      mm +/- 8.7. In the circumaortic venous ring group, the distance between the
      entrances of the retroaortic and preaortic limbs into the IVC was -39.0 mm +/-
      17.4; the distance between the entrance of the left retroaortic limb into the IVC
      and the confluence of the iliac veins was +63.2 mm +/- 17.1. CONCLUSIONS:
      Detailed knowledge of these anomalies is crucial for IVC filter placement,
      spermatic vein embolization, and adrenal or renal venous sampling.

PMID- 9540921
TI  - Percutaneous transthoracic needle biopsy of the lung: review of 612 lesions.
AB  - PURPOSE: The results and complications of 651 pulmonary fine-needle aspiration
      biopsies (FNABs) were reviewed. The number of needle passes and needle size were
      correlated to pneumothorax and chest tube placement rates. MATERIALS AND METHODS:
      FNAB of the lung was performed on 651 occasions in 612 patients with 18- to 22
      gauge Franseen needles. Diagnostic rates were calculated. The number of needle
      passes performed and needle size used were evaluated for their association with
      pneumothorax and subsequent chest tube placement. RESULTS: Diagnostic accuracy
      was 94% with sensitivity for malignancy of 95%. Positive and negative predictive
      values were 99.5% and 90%, respectively. Pneumothorax occurred in 26.9% of
      patients with 9.2% requiring chest tube placement. Increasing numbers of needle
      passes and larger needle sizes did not increase the rates of pneumothorax or
      chest tube placement. CONCLUSIONS: FNAB of the lung has excellent diagnostic
      rates and remains the procedure of choice for diagnosing pulmonary lesions. This
      large study contradicts perceptions that pneumothorax and chest tube placement
      rates decrease with thinner needles and fewer passes.

PMID- 9540922
TI  - Use of an abdominal compression device for CT-guided biopsy of enlarged abdominal
      or pelvic lymph nodes.

PMID- 9540923
TI  - Percutaneous transhepatic choledochocholedochostomy in the management of the
      postoperative patient.

PMID- 9540924
TI  - Removal of a broken syringe tip from a PICC hub.

PMID- 9540925
TI  - TIPS in portal vein occlusions: facilitation with percutaneous splenic access.

PMID- 9540926
TI  - Unclear choices in benign biliary stents.

PMID- 9540927
TI  - Neonatal nucleated red blood cell and lymphocyte counts in fetal brain injury.
AB  - OBJECTIVE: To determine whether neonatal lymphocyte or nucleated red blood cell
      (RBC) counts can be used to date fetal neurologic injury. METHODS: Singleton,
      term infants with hypoxic-ischemic encephalopathy, permanent neurologic
      impairment, and sufficient laboratory data were divided into two groups: infants
      with preadmission injury, manifested by a nonreactive fetal heart rate (FHR)
      pattern from admission until delivery; and infants with acute injury, manifested
      by a normal FHR pattern followed by a sudden prolonged FHR deceleration.
      Lymphocyte and nucleated RBC values were compared with published high normal
      counts for normal neonates: 8000 lymphocytes/mm3 and 2000 nucleated RBCs/mm3.
      RESULTS: The study population consisted of 101 neonates. In the first hours of
      life, lymphocyte counts were elevated among injured newborns, and then the counts
      rapidly normalized. Brain-injured neonates were 25 times more likely to have a
      lymphocyte count greater than 8000 than were normal neonates (54 [62%] of 87
      versus 6 [7%] of 84; odds ratio 25.5; 95% confidence interval 8.8, 80.1; P <
      .001). The mean lymphocyte count tended to be higher in the preadmission-injury
      group than in the acute-injury group. In comparison, nucleated RBC values were
      not correlated as strongly with neonatal hours of life; nucleated RBC counts
      tended to be higher and persist longer among neonates with preadmission injury
      than among those with acute injury. CONCLUSION: Compared with normal levels, both
      lymphocyte and nucleated RBC counts were elevated among neonates with fetal
      asphyxial injury. Both counts appear to be more elevated and to remain elevated
      longer in newborns with preadmission injury than in infants with acute injury.
      However, the rapid normalization of lymphocyte counts in these injured neonates
      limits the clinical usefulness of these counts after the first several hours of
      life.

PMID- 9540928
TI  - Umbilical cord plasma glutathione S-transferase alpha 1-1 levels as a marker of
      neonatal hepatocellular integrity.
AB  - OBJECTIVE: To investigate possible delivery-related impaired neonatal
      hepatocellular integrity by assessment of arterial and venous umbilical cord
      plasma levels of glutathione S-transferase Alpha 1-1. METHODS: Glutathione S
      transferase Alpha 1-1 levels were assessed in arterial and venous umbilical cord,
      and maternal venous plasma samples. The influence of maternal, delivery, and
      neonatal characteristics on arterial umbilical cord glutathione S-transferase
      Alpha 1-1 levels was studied, using linear regression analysis after log
      transformation. RESULTS: Median (range) arterial umbilical cord glutathione S
      transferase Alpha 1-1 plasma levels were higher than venous umbilical cord levels
      (9.68 [0.64-1125] microg/L and 7.66 [0.78-987.5] microg/L, respectively, P <
      .005). Median (range) arterial and venous umbilical cord glutathione S
      transferase Alpha 1-1 levels were higher than, and did not correlate with,
      maternal venous plasma levels (8.79 [1.79-183] microg/L and 6.47 [1.58-164.5]
      microg/L versus 1.47 [0.46-10.4] microg/L, P < .001). Neonates born vaginally
      demonstrated higher median (range) levels than those delivered by cesarean (13.41
      [1.02-1125] microg/L and 5.73 [0.64-172.90] microg/L, respectively, P < .001).
      Neonates with unfavorable pH (arterial pH under 7.20) demonstrated higher median
      (range) levels than those with normal pH (arterial pH at least 7.20) (15.15 [0.77
      1125] microg/L and 8.82 [0.64-120.90] microg/L, respectively, P < .001). Stepwise
      multiple linear regression analysis showed that birth weight had the largest
      influence on arterial umbilical cord glutathione S-transferase Alpha 1-1 levels,
      followed by arterial base deficit, and route of delivery. CONCLUSION: Arterial
      umbilical cord glutathione S-transferase Alpha 1-1 plasma levels, being unrelated
      to maternal venous levels, might give a reliable impression of early neonatal
      hepatocellular integrity and may become an additional indicator of neonatal
      condition immediately after birth.

PMID- 9540929
TI  - Right fetal cardiac axis: clinical significance and associated findings.
AB  - OBJECTIVE: To ascertain the clinical significance of right fetal cardiac axis.
      METHODS: Fetal cardiac axis was assessed prospectively in ultrasound examinations
      of 16,562 fetuses over a 6-year period. RESULTS: Twenty-two fetuses had a right
      cardiac axis. When classified by ventricular and atrial configuration, six
      fetuses had mirror-image hearts with situs inversus, 12 had rotation of the heart
      axis alone, and four had inversion of the ventricles. Fourteen of the 22 had
      underlying structural cardiac defects, most of which were atrioventricular septal
      defects, double outlet right ventricles, or common atria. The chromosomes and/or
      phenotypes of all 22 were normal. All four fetuses with polysplenia and asplenia
      died. Major extracardiac defects were few (two) but lethal. CONCLUSION: Right
      cardiac axis in the fetus is associated with a high incidence of structural
      cardiac defects. In the absence of severe extracardiac defects, polysplenia, or
      asplenia, neonatal outcome was good.

PMID- 9540930
TI  - Antenatal depiction of the fetal ear with three-dimensional ultrasonography.
AB  - OBJECTIVE: To evaluate the feasibility of examining the fetal ear with three
      dimensional ultrasound. METHODS: In 125 pregnancies between 19 and 38 weeks of
      gestation, fetal ears were evaluated by three-dimensional ultrasound. The volume
      images with surface rendering were analyzed to depict the morphology, lying axis,
      orientation, and cranial location of the fetal ears. RESULTS: Three-dimensional
      images of one or both ears were successfully reconstructed in 105 fetuses. Among
      them, 18 fetuses had anomalous ears. The anomalous ears, including microtia, low
      set ear with slope axis, abnormal ear orientation, and edematous ear, were
      confirmed after delivery. Three-dimensional ultrasound consistently displayed
      fetal ear abnormalities with greater accuracy and clarity. CONCLUSION: Because
      anomalous ears may be a part of complex fetal malformations, it is important to
      recognize ear abnormalities. Due to the complexity of the fetal ear, three
      dimensional ultrasound offers more important information than two-dimensional
      ultrasound, which simply gives auricular geometry. We suggest that three
      dimensional ultrasound can be used better to examine the fetal ear and may prove
      to be useful for prenatal diagnosis and genetic counseling.

PMID- 9540931
TI  - Prenatal diagnosis of the fetal Rhc genotype from peripheral maternal blood.
AB  - OBJECTIVE: To determine the fetal Rhc genotype by using the polymerase chain
      reaction (PCR) amplification procedure and maternal blood at the different steps
      of the fetal cell enrichment process. METHODS: Maternal peripheral venous blood
      samples were obtained from 11 pregnant women homozygous for the C antigen before
      amniocentesis. Three were not alloimmunized and eight were alloimmunized. The
      fathers were known to be heterozygous or homozygous for the c antigen by
      serologic testing. The mononuclear cell layer was isolated from maternal blood
      and flow sorted using monoclonal antibodies to CD36 or CD71 and glycophorin A.
      This was followed by PCR of the blood, mononuclear cells, and the sorted cells
      with allele-specific primers to RhCc genes. Gel electrophoresis was performed to
      predict fetal Rhc genotype. The fetal RhCc genotype was confirmed by serologic
      and DNA testing. RESULTS: All infants were positive for the Rhc gene. The
      positive fetal Rhc genotype was determined correctly in three of the 11 maternal
      blood samples without enrichment, in six of the nine mononuclear cell samples,
      and in seven of the eight sorted cell samples. The fetal genotype from one sorted
      sample was predicted to be homozygous C. One infant was determined by serology on
      cord blood to be negative for the c antigen, but repeated infant DNA
      amplification was consistent with the c genotype. CONCLUSION: Noninvasive fetal
      Rhc genotyping can be determined by PCR amplification of the rare fetal cells in
      maternal blood. These data reaffirm that enrichment of maternal blood for fetal
      cells is necessary to improve the sensitivity of the test.

PMID- 9540932
TI  - A prevalence survey of abuse and screening for abuse in urgent care patients.
AB  - OBJECTIVE: To determine the prevalence of physical and sexual abuse in pregnant
      and nonpregnant women in an urgent care obstetrics and gynecology triage unit and
      the frequency with which these patients recall being screened by their health
      care provider. METHODS: We carried out a structured survey of 255 pregnant and
      142 nonpregnant women presenting to an urban New England urgent care obstetrics
      and gynecology unit between February 1995 and September 1995. Patients in
      advanced stages of labor or unable to participate due to a language barrier were
      excluded. The survey consisted of 22 questions, seven of which were modified from
      the abuse assessment screen. RESULTS: Among 397 participants with complete data,
      we found that 184 (46%) reported a history of physical or sexual abuse in the
      past, and 38 (10%) reported recent abuse. Young age and insurance status
      (Medicaid or uninsured) were associated significantly with recent abuse after we
      controlled for race, education, and pregnancy status. Only 18% of women recalled
      being asked about abuse by a health care provider. Young women were more likely
      to report being asked about abuse. Among women reporting recent abuse, white
      women were significantly more likely to report being asked about abuse than
      nonwhite women (P=.02). The majority of women reporting a history of abuse did
      not recall being screened for violence by a health care provider. CONCLUSION:
      Women of all ages, income, and ethnic backgrounds reported a history of domestic
      violence or sexual assault. Providers should incorporate routine screening into
      the assessment of all women.

PMID- 9540933
TI  - Donor insemination and human immunodeficiency virus transmission.
AB  - OBJECTIVE: To describe cases of AIDS attributed to donor insemination identified
      through national human immunodeficiency virus (HIV)/AIDS surveillance and to
      compare the number identified through surveillance with our estimate of the
      number of women infected as a result of donor insemination before the initiation
      of donor screening. METHODS: We reviewed national HIV/AIDS surveillance data on
      women reported through December 1996 and described characteristics of documented
      and possible cases attributed to donor insemination. We estimated the number of
      women infected before the initiation of widespread screening of donors using
      assumptions about the number of women inseminated each year, the average number
      of inseminations, the proportion of donors who were men who had sex with men, the
      prevalence of HIV among such men, and the rate of transmission per HIV-infected
      exposure. RESULTS: A total of six documented and two possible cases of donor
      insemination-associated AIDS have been reported to the Centers for Disease
      Control and Prevention as of December 1996. An estimated eight to 141 women were
      infected through donor insemination in the United States between 1980 and 1984.
      Reasons for this discrepancy are discussed. CONCLUSION: Based on surveillance
      case reports and on our estimate, the total number of women infected as a result
      of donor insemination before screening was recommended is low. Current sperm bank
      practices to prevent HIV infection will be strengthened further by a pending
      proposal from the Food and Drug Administration requiring infectious disease
      screening and testing of semen donors. The most likely source of risk of new
      infections associated with donor insemination is self-insemination.

PMID- 9540934
TI  - Cost-effectiveness of routine antenatal varicella screening.
AB  - OBJECTIVE: To evaluate the cost-effectiveness of routine antenatal varicella
      serologic screening of pregnant women with negative or indeterminate varicella
      histories. METHODS: Routine antenatal varicella screening was evaluated using a
      decision analytic model. Outcomes were varicella cases, deaths, and life-years.
      Probabilities were derived from the literature, and sensitivity analysis was
      performed when data were imprecise or subject to variation. The analysis was
      repeated to include the effect of a policy of routine screening and vaccination
      of all adults. RESULTS: Routine antenatal varicella screening of history-negative
      women was not cost-effective unless the cost of screening was decreased six-fold,
      varicella exposure rates were greater than 6%, or there was a greater than three
      fold decrease in varicella exposure in women testing nonimmune compared with
      unscreened women. These results were not sensitive to alterations in varicella
      zoster immunoglobulin (Ig) effectiveness, varicella communicability, rates and
      timing of contact reporting, costs (per case, pneumonia, and death), or serologic
      test performance. If performed as part of a policy of universal screening of all
      history-negative adults (with vaccination of the majority of those testing
      nonimmune), routine antenatal varicella testing became cost-effective.
      CONCLUSION: Routine antenatal varicella screening of all pregnant women with
      negative or indeterminate varicella histories is not cost-effective. It could be
      cost-effective in groups of women with increased exposure risk, or if part of a
      policy of screening and vaccination of all adults.

PMID- 9540935
TI  - A cost-effectiveness analysis of prenatal carrier screening for cystic fibrosis.
AB  - OBJECTIVE: To examine the cost-effectiveness of prenatal carrier screening for
      cystic fibrosis. METHODS: A cost-benefit equation was developed that was based on
      the hypothesis that the cost of prenatal diagnosis required to diagnose and
      prevent one case of cystic fibrosis should be equal to or less than the lifetime
      cost generated from the birth of a neonate with cystic fibrosis. The formula was
      adjusted because a woman's positive or negative carrier status remains unchanged,
      thus eliminating the need for testing in subsequent pregnancies. The formula was
      manipulated to identify the optimal cost per screening test, as well as the net
      cost savings per prenatally diagnosed case of cystic fibrosis for various racial
      or ethnic groups. Sensitivity analyses included some key assumptions regarding
      the cost per screening test ($50-150), patient screening acceptance rates (25
      100%), and therapeutic abortion rates (50-100%). RESULTS: Assuming therapeutic
      abortion rates of 50-100%, the net savings per prenatally diagnosed case of
      cystic fibrosis are $58,369-$382,369 among whites. Given the previously reported
      patient screening acceptance rates of 50-78%, the overall annual cost savings in
      the United States for whites are $161-251 million. However, the screening program
      was not found to be cost-effective for blacks, Asians, or Hispanics. CONCLUSION:
      Under most assumptions and sensitivity analyses, a prenatal cystic fibrosis
      carrier screening program appears to be cost-effective.

PMID- 9540936
TI  - An economic evaluation of first-trimester genetic sonography for prenatal
      detection of Down syndrome.
AB  - OBJECTIVE: To determine 1) the diagnostic accuracy requirements of first
      trimester genetic sonography from the cost-benefit point of view and 2) the
      economic impact of first-trimester genetic sonography for the United States on
      the basis of the accuracy of previously published studies. METHODS: A cost
      benefit equation was developed on the basis of the hypothesis that the cost of
      chorionic villus sampling (CVS) in pregnant women with advanced maternal age (at
      least 35 years old) should be at least equal to the cost of genetic sonography
      with CVS used only for those with abnormal ultrasound results. The components of
      the equation included the diagnostic accuracy of genetic ultrasound (sensitivity
      and specificity for detecting Down syndrome), the costs of the CVS package and
      genetic ultrasound, and the lifetime cost of Down syndrome cases. RESULTS: First
      trimester genetic sonography was found to be beneficial if the overall
      sensitivity for detecting Down syndrome was greater than 70%, and even then, the
      cost-benefit ratio depended on the corresponding false-positive rate. The
      required minimum ultrasound sensitivity varied according to the maternal age
      specific prevalence of Down syndrome and ranged between 40% (for women 35 years
      old) to 96% (for women 44 years old). Of eight published cohorts using nuchal
      translucency thickness for genetic sonography, five had accuracies of genetic
      ultrasound compatible with net benefits. CONCLUSION: The benefits of first
      trimester genetic sonography depend on its diagnostic accuracy. First-trimester
      genetic sonography has the potential for annual savings of 22 million dollars in
      the United States.

PMID- 9540937
TI  - Human immunodeficiency virus test refusal in pregnancy: a challenge to voluntary
      testing.
AB  - OBJECTIVE: To determine if awareness of methods to reduce vertical transmission
      of human immunodeficiency virus (HIV) is associated with HIV test acceptance and
      to clarify patients' attitudes toward routine versus elective prenatal HIV
      testing. METHODS: In a cross-sectional study, 247 antenatal patients were
      surveyed regarding HIV knowledge, self-perceived HIV risk, and willingness to
      learn a positive test result. This information, along with demographic and risk
      factor data, was related to HIV test acceptance. Patients also indicated their
      attitudes toward routine versus elective prenatal testing for HIV and other
      common prenatal screening tests. RESULTS: Seventy-two percent of antenatal
      patients accepted HIV testing. Test acceptance was not associated with the
      presence of risk factors, self-perceived HIV risk, or demographic factors,
      including race and ethnicity. Test acceptance was associated positively with
      patients' knowledge of a medical intervention to reduce vertical transmission and
      their willingness to learn a positive HIV test result. Only 24% of patients knew
      that the risk of vertical transmission could be reduced using medication. Sixty
      nine percent of patients said that prenatal HIV testing should be routine,
      whereas 27% said that it should be done only after specific written consent. As a
      group, our patients viewed HIV screening no differently from screening for other
      infections in pregnancy. CONCLUSION: Interventions aimed at increasing HIV
      testing rates among pregnant women should focus on educating patients about
      vertical transmission reduction and promising new therapies for HIV infection.
      Proponents of elective testing should re-evaluate the assumption that patients
      view HIV testing differently from other prenatal tests for which separate written
      consent is not required.

PMID- 9540938
TI  - Management of twin pregnancies consisting of a complete hydatidiform mole and
      normal fetus.
AB  - OBJECTIVE: To report the clinical features, management, and outcome of twin
      pregnancies consisting of a complete hydatidiform mole and a coexisting normal
      fetus. METHODS: Between 1966 and 1997, seven women with complete hydatidiform
      mole and coexisting normal fetus were treated at the John I. Brewer Trophoblastic
      Disease Center of Northwestern University Medical School. Clinical features,
      including presenting symptoms, gestational dates, hCG levels, and complications,
      as well as route of delivery or evacuation, pregnancy outcome, genetic analysis,
      and need for chemotherapy were assessed. RESULTS: Four women required uterine
      evacuation before 20 weeks' gestation because of vaginal bleeding or medical
      complications, one woman required an emergency hysterotomy because of hemorrhage
      at 24 weeks, and two women delivered normal, viable infants at 26 and 34 weeks.
      The pathologic diagnosis of complete hydatidiform mole was confirmed in each case
      and the chromosome complement was 46,XX in all molar gestations. Four of seven
      women required chemotherapy for treatment of nonmetastatic gestational
      trophoblastic tumors, including both women who delivered viable infants and two
      of the five women whose pregnancies were evacuated before 24 weeks' gestation.
      All four patients were treated with five to seven cycles of a 5-day methotrexate
      regimen and achieved complete remission. CONCLUSION: Patients with a twin
      pregnancy consisting of a complete mole and a normal fetus are at increased risk
      for hemorrhage and medical complications, as well as the development of
      persistent gestational trophoblastic tumor.

PMID- 9540939
TI  - Cervical cancer screening among women with and without hysterectomies.
AB  - OBJECTIVE: To compare the rate of Papanicolaou testing in a population-based
      sample of women with medical documentation of 1) total hysterectomy for benign
      conditions, 2) total hysterectomy for malignant conditions, and 3) hysterectomy
      with cervix intact to rates among women who had not had a hysterectomy. METHODS:
      The Marshfield Epidemiologic Study Area was used to identify a retrospective
      cohort of women with hysterectomies age-matched to women without hysterectomies.
      This study compares the Papanicolaou test rate per year (outcome) by hysterectomy
      status (exposure) for women with total hysterectomy for benign reasons (n=197),
      total hysterectomy for malignancy (n=75), supracervical hysterectomy (n=43), and
      no hysterectomy (n=315). RESULTS: Compared with women who did not have a
      hysterectomy (nonexposed), women with a hysterectomy (exposed) for benign reasons
      had significantly fewer Papanicolaou tests; on average, one less test every 3
      years (mean difference=-0.34 tests/year, P < .001). Contrary to this, women with
      a malignancy-related hysterectomy had significantly more tests than their
      nonexposed counterparts (mean difference=0.87 tests/year, P < .001); nearly one
      additional test per year. Finally, women with supracervical hysterectomies had
      the same rate of testing as their nonexposed counterparts (mean difference=-0.03
      tests/year, P=.62); on average, one test every 2.5 years. CONCLUSION: This study
      demonstrates that Papanicolaou testing rates vary by type and reason for
      hysterectomy. Women with hysterectomies for benign reasons may be receiving from
      two to three times as many tests as needed. Notably, women with intact cervices
      following hysterectomy have similar testing rates (one every 2.5 years) as women
      without hysterectomies. This has direct implications for leaving a woman's cervix
      intact given normal cytology at the time of hysterectomy.

PMID- 9540940
TI  - Analysis of atypical squamous (glandular) cells of undetermined significance
      smears by neural network-directed review.
AB  - OBJECTIVE: The objective of this study was to evaluate the value of neural
      network-directed review of smears determined to contain atypical squamous
      (glandular) cells of undetermined significance to identify those cases most
      likely to be associated with cervical intraepithelial neoplasia. METHODS: One
      hundred sixty smears reported as atypical squamous (glandular) cells of
      undetermined significance on patients having colposcopy and directed biopsy
      within 1 year of the smear were identified. The smears were subjected to a neural
      network-directed review and classified according to findings on this review. The
      latter findings were related to those obtained on cervical biopsy. RESULTS: One
      hundred sixty smears originally reported as atypical squamous (glandular) cells
      of undetermined significance were subjected to neural network-directed review.
      The smears were upgraded in 20.6% of cases. Ninety-one patients were found to
      have normal biopsies, and 69 had biopsies reported as abnormal. Of the smears in
      patients with abnormal biopsies, 37.7% were upgraded, whereas only 7.7% of smears
      from those with normal biopsies were upgraded (P < .001). Nine patients were
      found to have cervical intraepithelial neoplasia-3 on biopsy. Six of the nine
      smears (66.7%) taken on these patients were upgraded. CONCLUSION: Neural network
      directed analysis of smears conventionally diagnosed as atypical squamous
      (glandular) cells of undetermined significance will reveal findings suggesting a
      squamous intraepithelial lesion in a significant number of cases. This approach
      requires further study because it is a relatively cost-effective means of
      triaging patients with a cytologic diagnosis of atypical squamous (glandular)
      cells of undetermined significance.

PMID- 9540941
TI  - Comparison of transvaginal color Doppler imaging and color Doppler energy for
      assessment of intraovarian blood flow.
AB  - OBJECTIVE: To investigate any systematic differences in the analysis of blood
      flow velocity waveforms derived by color Doppler imaging and color Doppler energy
      examination of corpora lutea and adnexal tumors, to test whether the accuracy for
      diagnosing ovarian malignancy differs between end points derived by color Doppler
      imaging and color Doppler energy, and to compare the reproducibility of flow
      velocity waveform analysis obtained by both methods. METHODS: Fifty-six
      asymptomatic women with presumed corpora lutea and 67 women with known adnexal
      masses were included in the study. They all were examined using transvaginal
      sonography with color Doppler imaging and color Doppler energy. Pulsed Doppler
      sonography was used to obtain flow velocity waveforms to determine the
      pulsatility index (PI), resistance index (RI), peak systolic velocity, and time
      averaged maximum velocity. The tumors were classified retrospectively according
      to histologic criteria. RESULTS: There were 52 women with benign, three with
      borderline, and 12 with malignant ovarian tumors. Repeated-measures analysis of
      variance revealed no systematic differences in the values of all four
      measurements performed under color Doppler imaging and color Doppler energy for
      all cases of corpora lutea and adnexal tumors (PI: P=.153, RI: P=.197, peak
      systolic velocity: P=.355, time-averaged maximum velocity: P=.159). All cases of
      borderline and malignant tumors had detectable pulsatile blood flow with color
      Doppler imaging and color Doppler energy. Forty-two (80.8%) of the benign tumors
      had flow detectable with color Doppler imaging, compared with 40 (76.9%) with
      color Doppler energy (P=.480). Analysis of receiver operating characteristic
      curves showed a marginal but nonsignificant improvement in diagnostic performance
      with color Doppler energy compared with color Doppler imaging for all four
      measurements (PI: P=.182, RI: P=.178, peak systolic velocity: P=.254, time
      averaged maximum velocity: P=.238). The intraclass correlation coefficients for
      all four measurements were superior with color Doppler imaging compared with
      color Doppler energy. CONCLUSION: Flow velocity waveform analysis and diagnostic
      accuracy for ovarian malignancy are not significantly different between color
      Doppler imaging and color Doppler energy. Examinations with color Doppler imaging
      appear to be more reproducible than those with color Doppler energy.

PMID- 9540942
TI  - Alteration of telomerase activity associated with development and extension of
      epithelial ovarian cancer.
AB  - OBJECTIVE: To assess telomerase activity associated with the development and
      extension of epithelial ovarian cancer and to investigate the relationship
      between p53 gene status and telomerase activity. METHODS: A total of 53 samples
      (41 epithelial ovarian cancers, five borderline epithelial tumors, four benign
      adenomas, and three surface epithelia) were examined for telomerase activity by
      the polymerase chain reaction (PCR) -based telomeric repeat amplification
      protocol assay. Mutations in the p53 gene were determined by PCR-single strand
      conformation polymorphism analysis. RESULTS: Telomerase activity was detected in
      33 of 41 epithelial ovarian cancers and in three of five borderline malignancies
      but was not detectable in either benign tumors or normal surface epithelium. The
      mean (+/-standard deviation [SD]) intensity of telomerase activity in cancers was
      significantly higher than that in borderline malignancies (10.6+/-8.2 versus 3.6
      4+/-1.3). The positivity of telomerase activity did not correlate with any
      clinical findings, but the intensity (+/-SD) of telomerase activity was
      significantly higher in tumors with lymph node involvement (12.2+/-8.3 versus
      3.8+/-1.1). Mutations of the p53 gene were observed in 44% of ovarian cancers;
      p53 gene status did not relate to telomerase activity. Multivariate analysis
      showed that the intensity of telomerase activity was not an independent factor
      for prognosis of patients with ovarian cancer. CONCLUSION: Telomerase activity
      may be associated with development and extension of epithelial ovarian cancer.

PMID- 9540943
TI  - Vestibular nerve fiber proliferation in vulvar vestibulitis syndrome.
AB  - OBJECTIVE: To evaluate nerve fiber density in vestibular specimens from women
      operated upon for vulvar vestibulitis. METHODS: Forty-seven women with vulvar
      vestibulitis syndrome underwent modified posterior vestibulectomies. Vestibular
      specimens were analyzed after being stained for S-100 neural tissue protein.
      Women were followed up for 2 years. RESULTS: In specimens from 44 of 47 patients,
      the densities and numbers of nerve fibers per square unit in the preparations
      were greater than those in specimens from six control women. In the patients, a
      statistically significant linear correlation was found between inflammation and
      nerve bundle density in the preparations (Spearman rank correlation coefficient
      rs=.41; P=.005). There were no signs of infectious etiology in any preparation.
      No or slight postoperative dyspareunia was reported by 38 of 42 women after 6
      months, 36 of 39 after 12 months, and 26 of 28 after 24 months. CONCLUSION:
      Vestibular neural hyperplasia may provide a morphologic explanation of the pain
      in vulvar vestibulitis syndrome.

PMID- 9540944
TI  - Effect of preoperative voiding mechanism on success rate of autologous rectus
      fascia suburethral sling procedure.
AB  - OBJECTIVE: To evaluate the efficacy of the rectus fascia suburethral sling
      procedure and to determine whether preoperative voiding caused by the Valsalva
      maneuver is a risk factor for short-term objective failure. METHODS: This study
      is a retrospective chart review of 50 patients who underwent the suburethral
      sling procedure with rectus fascia at our institution between March 1994 and
      August 1996. All patients had genuine stress incontinence with intrinsic
      sphincteric deficiency or urethral hypomobility. Preoperative multichannel
      urodynamics were measured in all patients, and postoperative urodynamic testing
      was done at 3 months in 48 patients. RESULTS: Ninety-four percent of patients
      were cured subjectively of stress urinary incontinence at 3 months. Objective
      cure was found by urodynamic measurements in 73% of the 48 patients who underwent
      postoperative testing. There was an increased risk of objective failure in
      patients whose voiding preoperatively was caused by the Valsalva maneuver.
      Objective failure was found at 3 months in 54% of the 13 patients in the Valsalva
      group, compared with 17% of the 35 in the non-Valsalva group (P=.011). Patients
      in the Valsalva group also tended to have longer durations of postoperative
      catheterization than did patients in the non-Valsalva group (P=.049). CONCLUSION:
      The rectus fascia suburethral sling procedure appears to be an effective
      operation for the treatment of genuine stress incontinence in carefully selected
      patients. However, patients who are identified preoperatively as voiding because
      of the Valsalva maneuver have a higher failure rate for this procedure.

PMID- 9540945
TI  - Intraoperative hypothermia and post-cesarean wound infection.
AB  - OBJECTIVE: To determine whether intraoperative hypothermia during cesarean
      delivery is a risk factor for wound infection. METHODS: Eighteen cases with wound
      infection and 18 controls matched for age, weight, presence of gestational
      hypertension, and surgery length were selected from a cohort of 900 women who
      underwent cesarean delivery and who were assessed for wound infection according
      to strict criteria. Because immediate postoperative temperatures reflect
      intraoperative temperature nadir accurately and were available universally, we
      compared the mean immediate postoperative temperatures between cases and
      controls. RESULTS: In addition to the intentionally matched factors, the groups
      were well-matched for race, parity, presence of labor, presence of meconium, and
      duration of membrane rupture. The mean initial postoperative temperatures were
      similar between the two groups (36.3+/-0.9C versus 36.6+/-1.0C, respectively;
      P=.8). This study had a power of 90% to detect an intergroup difference of 1C.
      CONCLUSION: In this case-control study of cesarean delivery, intraoperative
      hypothermia was not a risk factor for wound infection.

PMID- 9540946
TI  - Prevention of preeclampsia by linoleic acid and calcium supplementation: a
      randomized controlled trial.
AB  - OBJECTIVE: To determine the effect of low doses of linoleic acid and calcium on
      prostaglandin (PG) levels and the efficacy of this treatment in the prevention of
      preeclampsia. METHODS: In a randomized, double-blind, placebo-controlled study we
      treated 86 primigravidas with risk factors for preeclampsia (high biopsychosocial
      risk [above 3 points], positive roll-over test, and high mean blood pressure
      [above 85 mmHg)] with daily doses of either 450 mg linoleic acid and 600 mg
      calcium (n=43) or 450 mg starch and 600 mg lactose placebo (n=43) during the
      third trimester of pregnancy. RESULTS: Four women in the experimental group
      (9.3%) developed preeclampsia compared with 16 (37.2%) controls (relative risk
      0.25, 95% confidence interval 0.09, 0.69, P < .001). The median serum levels of
      PGE2 after 4 weeks of treatment increased by 106% in the experimental group
      (P=.03) and decreased by 33% in the control group (P=.02). The median ratio
      between thromboxane B2 and PGE2 decreased by 40% in the experimental group
      (P=.02) and increased by 18% in the control group (P=.14). No significant
      differences were observed in the median ratio between thromboxane B2 and 6-keto
      PGF1alpha in either group. No serious maternal or neonatal side effects of
      treatment occurred in either group. CONCLUSION: The administration of low daily
      doses of linoleic acid and calcium during the third trimester of pregnancy
      reduced the incidence of preeclampsia significantly in women at high risk,
      possibly by correcting the PGE2 levels.

PMID- 9540947
TI  - Platelet angiotensin II binding sites and early detection of preeclampsia.
AB  - OBJECTIVE: To determine if platelet angiotensin II binding density during the
      second or third trimester of pregnancy can be used as a marker for early
      detection of women who will develop preeclampsia. METHODS: We collected blood
      samples from 412 nulliparous pregnant women during their second or third
      trimesters. They were classified in four groups after delivery: normotensive
      (n=297), transient hypertensive (n=54), preeclamptic (n=39), and chronic
      hypertensive (n=22). We also studied 35 nonpregnant women and 122 women in the
      peripartum period. The binding capacity of platelet angiotensin II receptors was
      analyzed in each patient. RESULTS: In normotensive pregnancies, there was a
      significant decrease in mean (+/-standard error of the mean [SEM]) platelet
      binding in the second trimester (1.6+/-0.2 fmol/10(9) cells) compared with
      nonpregnant women (3.3+/-0.7 fmol/10[9] cells). No statistical differences were
      observed in the mean (+/-SEM) number of platelet angiotensin II binding sites
      between the groups studied in the third trimester (normal: 1.7+/-0.1 fmol/10(9)
      cells; transient hypertensive: 2.3+/-0.4 fmol/10(9) cells; preeclamptic: 1.6+/
      0.4 fmol/10(9) cells, and chronic hypertensive: 1.6+/-0.6 fmol/10(9) cells), nor
      were any significant differences found in second-trimester values. At cutoff
      levels providing identical sensitivities, angiotensin II binding showed
      significantly lower positive predictive values than mean arterial pressure (P <
      .05). With this study's sample size, we could have demonstrated an improvement in
      positive predictive values of 20% with a statistical power (1-beta) of 90%.
      CONCLUSION: The measurement of platelet angiotensin II receptor density cannot be
      recommended for the early detection of preeclampsia.

PMID- 9540948
TI  - Correlation between fasting glucose in the first trimester and glucose challenge
      test in the second.
AB  - OBJECTIVE: To determine if there is a statistically significant correlation
      between the plasma glucose level obtained following a glucose challenge test at
      24-28 weeks' gestation and the fasting plasma glucose level in the first
      trimester. METHODS: The study population included 621 healthy women with
      singleton pregnancies followed in the antenatal clinic of the Hadassah Medical
      Center, with a fasting plasma glucose level performed during the first trimester.
      Nine women had fasting blood glucose levels above 105 mg/dL and were excluded
      from the study. Of the remaining 612 women, 425 (69%) had 50-g glucose challenge
      tests at 24-28 weeks' gestation. RESULTS: The mean (+/-standard deviation [SD])
      first-trimester fasting glucose level was 77.8+/-9.7 mg/dL and the mean (+/-SD)
      glucose level 1 hour after the second-trimester glucose challenge test was
      109.1+/-29.8 mg/dL. The fasting plasma glucose level and the glucose level
      following the glucose challenge correlated significantly but not strongly (=.26,
      P < .001). However, using a linear regression model in which fasting plasma
      glucose level and maternal weight were explanatory variables and glucose level
      following the glucose challenge test was the dependent variable resulted in a
      very low r2 (.10). CONCLUSION: The correlation between the plasma glucose level
      obtained following a glucose challenge test and the fasting plasma glucose level
      in the first trimester is low, indicating that fasting glucose measurement early
      in pregnancy has no clinical benefits.

PMID- 9540949
TI  - The effects of carbohydrate restriction in patients with diet-controlled
      gestational diabetes.
AB  - OBJECTIVE: To determine the effect of carbohydrate restriction on perinatal
      outcome in patients with diet-controlled gestational diabetes mellitus (GDM).
      METHODS: Women with diet-controlled GDM were divided non-randomly into two groups
      based on their dietary carbohydrate content: those with low dietary carbohydrate
      content (below 42%) and those with high dietary carbohydrate content (exceeding
      45%). Subjects kept dietary accounts and were followed with daily fasting and
      postprandial glucose assessments. Subjects also were tested daily for urinary
      ketones. Glycosylated hemoglobin, mean fasting and postprandial glucose values,
      incidence of macrosomia and large for gestational age (LGA) infants, cesarean
      deliveries for cephalopelvic disproportion and macrosomia, and need for insulin
      therapy were compared between the groups. RESULTS: The two groups were identical
      in terms of demographic characteristics. Significant reductions in the
      postprandial glucose values were seen among subjects in the low-carbohydrate
      group (P < .04). Fewer subjects in the low-carbohydrate group required the
      addition of insulin for glucose control (P < .047; relative risk [RR] 0.14; 95%
      confidence interval [CI] 0.02, 1.00). The incidence of LGA infants was
      significantly lower in the low-carbohydrate group (P < .035; RR 0.22; 95% CI
      0.05, 0.91). Subjects in the low carbohydrate group also had a lower rate of
      cesarean deliveries for cephalopelvic disproportion and macrosomia (P < .037; RR
      0.15; 95% CI 0.04, 0.94). CONCLUSION: Carbohydrate restriction in patients with
      diet-controlled GDM results in improved glycemic control, less need for insulin
      therapy, a decrease in the incidence LGA infants, and a decrease in cesarean
      deliveries for cephalopelvic disproportion and macrosomia.

PMID- 9540950
TI  - Elevated second-trimester maternal serum hCG: a marker of inadequate
      angiogenesis.
AB  - OBJECTIVE: To measure angiogenin, a potent inducer of neovascularization and
      interleukin-6, as an indicator of acute inflammation, in second-trimester
      amniotic fluid of patients with elevated maternal serum hCG. METHODS: In this
      case-control study, 20 patients with elevated maternal serum hCG (at least 2.0
      multiples of median) at triple screen were matched 2:1 with controls on the basis
      of year of amniocentesis, parity, and race. Inclusion criteria were 1) singleton
      gestation, 2) no evidence of anomalies, and 3) genetic amniocentesis. Amniotic
      fluid was immunoassayed for angiogenin and interleukin-6. The immunoassay
      sensitivity for angiogenin was 0.026 ng/mL, interassay coefficient of variation
      4.6%, and intra-assay coefficient of variation 2.9%. For interleukin-6, the
      immunoassay sensitivity was 2.37 pg/mL, interassay coefficient of variation 2.7%,
      and intra-assay coefficient of variation 1.9%. Angiogenin and interleukin-6
      values were normalized by using natural log transformation for statistical
      analysis. Statistical analysis included analysis of variance and stepwise
      regression, with P < .05 significant. RESULTS: After correcting (by multivariate
      regression) for gestational age at sampling and nulliparity, amniotic fluid
      angiogenin levels were significantly lower in the study subjects than in controls
      (26%+/-11% lower, P=.004), whereas the interleukin-6 levels did not change
      significantly (34%+/-40% lower, P=.3). CONCLUSION: Amniotic fluid angiogenin
      levels are significantly lower in patients with elevated maternal serum hCG at
      triple screen, suggesting inadequate angiogenesis, but interleukin-6 values do
      not differ significantly.

PMID- 9540951
TI  - Depot medroxyprogesterone acetate or oral contraception in postpartum
      adolescents.
AB  - OBJECTIVE: To compare rates of method continuation and repeat pregnancy among
      postpartum adolescents selecting depot medroxyprogesterone acetate or oral
      contraceptives (OCs). METHODS: A retrospective study of 161 adolescents aged 19
      years and younger who gave birth at an urban teaching hospital between May 1,
      1994, and April 30, 1995, returned to the hospital's family planning clinic
      within 14 weeks of delivery and chose depot medroxyprogesterone acetate (n=111,
      69%), or OC (n=50, 31%) as their postpartum contraceptive method. Most subjects
      were black (99%), single (97%), and on medical assistance (85%). Data were
      gathered 12-18 months postpartum (mean+/-standard deviation [SD] 14.5+/-1.6
      months) by telephone interview and medical record review. The main outcome
      measures were method continuation and repeat pregnancy. RESULTS: The mean (+/-SD)
      age at delivery was 17.8+/-1.4 years. Variables differentiating subjects
      selecting depot medroxyprogesterone acetate or OC included multiparity (34%
      versus 12%, P < .05), mean age at first pregnancy (15.9 versus 16.6 years, P <
      .05), and mean age at first delivery (16.1 versus 16.9 years, P < .05). The
      survival curves for depot medroxyprogesterone acetate and OC continuation
      differed significantly (median duration of use 8.1 versus 5.4 months,
      respectively), but the continuation rates at 12 months were similar (34% versus
      32%). The survival curves for repeat pregnancy among subjects selecting depot
      medroxyprogesterone acetate differed significantly from curves of those choosing
      OC, with repeat pregnancy rates of 15% and 36% by 15 months. Postpartum selection
      of OC was the only variable entering a Cox regression model designed to predict
      repeat pregnancy (relative risk 3.0, 95% confidence interval 1.4, 6.7).
      CONCLUSION: Adolescent mothers choosing depot medroxyprogesterone acetate or OC
      immediately postpartum face similarly high rates of method discontinuation and
      repeat pregnancy within 1 year.

PMID- 9540952
TI  - Hyperemesis gravidarum associated with Helicobacter pylori seropositivity.
AB  - OBJECTIVE: To test the hypothesis that infection with Helicobacter pylori is
      associated with hyperemesis gravidarum. METHODS: From January 1995 to November
      1996 we enrolled 105 patients with hyperemesis gravidarum in a prospective study.
      The Helicobacter serum Immunoglobulin (Ig) G concentrations in these patients
      were compared with those in asymptomatic gravidas matched for week of gestation.
      RESULTS: Positive serum IgG concentrations were found in 95 of the 105
      hyperemesis patients (90.5%) compared with 60 of 129 controls (46.5%). A chi2
      test showed statistical significance (P < .001). The mean (+/-standard deviation)
      index percentages of the IgG titers were 74.2+/-23.6% in the hyperemesis group
      and 24.3+/-4.4% in the control group (P < .01, Student t test). CONCLUSION:
      Infection with H pylori may cause hyperemesis gravidarum.

PMID- 9540953
TI  - A two-term MEDLINE search strategy for identifying randomized trials in
      obstetrics and gynecology.
AB  - OBJECTIVE: To develop and test a simple MEDLINE search strategy for
      identification of randomized controlled trials (RCTs) in obstetrics and
      gynecology. METHODS: To develop our search strategy, we asked clinicians in our
      department to indicate, from a list of search terms, the terms they would use to
      identify RCTs in MEDLINE. The two most common terms, controlled-clinical-trial
      (publication type) and randomized-controlled-trial (publication type), were
      combined with the link word, OR, and then used to identify RCTs in four
      obstetrics and gynecology journals for the years 1975, 1980, 1985, 1990, and
      1995. Concurrently, a handsearch of these same journals and years was performed
      to identify RCTs. The sensitivity and precision of MEDLINE and handsearch were
      calculated using the total number of RCTs identified by both methods as a
      reference standard. Sensitivity is the RCTs identified by search strategy as a
      percentage of all RCTs identified by reference standard. Precision is the RCTs
      identified by a search strategy as a percentage of all articles identified by it.
      RESULTS: The overall sensitivity of our MEDLINE search strategy was 72.5%, and
      the precision was 83.4%. Over 2 decades, sensitivity of our MEDLINE search
      increased from 0% to 94.9% (P < .001), while its precision dropped from 100% to
      75.5% (P=.003). For 1990 and 1995 combined, sensitivity and precision of our
      MEDLINE search strategy were 90.3% and 79.6%, respectively. Overall sensitivity
      for handsearch was 96.5%; its precision was 5.0%. Over 2 decades, the sensitivity
      of handsearch dropped insignificantly from 100% to 92.3% (P=.05), while the
      precision increased from 2.6% to 6.3% (P < .001). CONCLUSION: Our simple MEDLINE
      search strategy has a high sensitivity and precision, especially in more recent
      years. Obstetricians and gynecologists may use it to search quickly for RCTs to
      guide patient care.

PMID- 9540954
TI  - The case against using ordinal numbers for gestational age.
AB  - OBJECTIVE: Use of ordinal numbers (eg, twelfth) instead of cardinal numbers (eg,
      twelve) to measure gestational age often leads to clinical confusion. We
      conducted this study to document the prevalence of ambiguous or contradictory use
      of ordinal numbers for gestational age and to discuss some clinical implications.
      MATERIALS AND METHODS: We reviewed a convenience sample of standard texts in
      obstetrics and in abortion and examined a random sample of articles on abortion.
      RESULTS: Imprecise or incorrect use of ordinal numbers for gestational age was
      common: Eight of nine (89%) obstetrics texts and all six abortion texts had this
      problem. The corresponding figure for the abortion articles was 32 of 88 (36%).
      CONCLUSION: Use of ordinal numbers for gestational age introduces information
      bias (misclassification) into the scientific literature. More importantly, it may
      lead to clinical errors related to the timing of administration of antenatal
      corticosteroids and the upper limit for induced abortions. Gestational age
      measurements should use only cardinal numbers (eg, twelve) of completed days or
      weeks from the last menstrual period. Clinicians should abandon use of ordinal
      numbers for gestational age.

PMID- 9540955
TI  - Colposcopy for the diagnosis of squamous intraepithelial lesions: a meta
      analysis.
AB  - OBJECTIVE: To quantify by meta-analysis the performance of colposcopy to set a
      standard against which new technologies can be compared. DATA SOURCES: MEDLINE
      was searched for articles on colposcopy for diagnosis of squamous intraepithelial
      lesions (SIL). The search selected articles from 1960 to 1996 combining the key
      word "colposcopy" with key words "diagnosis," "positive predictive value,"
      "negative predictive value," "likelihood ratio," and "receiver operating
      characteristic (ROC) curve." METHODS OF STUDY SELECTION: Articles were selected
      if the authors studied a population of patients with abnormal screening
      Papanicolaou smears and presented raw data showing for each cervical lesion type
      the number of patients judged positive and negative by colposcopic impression
      versus the standard of colposcopic biopsy results. Nine of 86 studies met these
      criteria. TABULATION, INTEGRATION, AND RESULTS: Biopsies had been categorized as
      normal, atypia, cervical intraepithelial neoplasia (CIN) I, CIN II, CIN III,
      carcinoma in situ, and invasive cancer; we recalculated performance measures
      using the Bethesda system. Overall sensitivity, specificity, likelihood ratios,
      ROC curves, and the corresponding areas under the curves were calculated. The
      average weighted sensitivity of diagnostic colposcopy for the threshold normal
      compared with all cervix abnormalities (atypia, low-grade SIL, high-grade SIL,
      cancer) was 96% and the average weighted specificity 48%. For the threshold
      normal cervix and low-grade SIL compared with high-grade SIL and cancer, average
      weighted sensitivity was 85% and average weighted specificity 69%. Likelihood
      ratios generated small but important changes in probability for distinguishing
      normal cervix and low-grade SIL from high-grade SIL and cancer. Areas under the
      ROC curve were 0.80 for the threshold normal cervix compared with all
      abnormalities and 0.82 for the threshold normal cervix and low-grade SIL compared
      with high-grade SIL and cancer. CONCLUSION: Colposcopy compares favorably with
      other medical diagnostic tests in terms of sensitivity, specificity, and area
      under the ROC curve. New diagnostic methods for the cervix can be compared with
      colposcopy using these quantified values.

PMID- 9540956
TI  - Biblical twins.

PMID- 9540957
TI  - Nitroglycerin to facilitate fetal extraction during cesarean delivery.

PMID- 9540958
TI  - Significance of a false-positive trisomy 18 multiple-marker screening test.

PMID- 9540959
TI  - Random protein: creatinine ratio for the quantitation of proteinuria in
      pregnancy.

PMID- 9540960
TI  - Human papillomavirus type 16 and risk of preinvasive and invasive vulvar cancer:
      results from a seroepidemiological case-control study.

PMID- 9540961
TI  - Pregnancy outcomes in women with gestational diabetes compared with the general
      obstetric population.

PMID- 9540962
TI  - Pregnancy outcomes in women with gestational diabetes compared with the general
      obstetric population.

PMID- 9540963
TI  - Random protein-creatinine ratio for the quantitation of proteinuria in pregnancy.

PMID- 9540964
TI  - A prospective evaluation of fetal pericardial fluid in 506 second-trimester low
      risk pregnancies.

PMID- 9540965
TI  - A prospective evaluation of fetal pericardial fluid in 506 second-trimester low
      risk pregnancies.

PMID- 9540966
TI  - Occurrence of hepoxilins and trioxilins in psoriatic lesions.
AB  - We recently found that normal human epidermis produces relatively high amounts of
      hepoxilins and trioxilins in vitro. Therefore, the aim of this study was to
      demonstrate the presence of these compounds in psoriatic lesions. Extracts from
      scales of patients with chronic stable plaque psoriasis were analyzed by a
      combination of high performance liquid chromatography and gas chromatography-mass
      spectrometry techniques. We found that the levels of hepoxilin B3 were more than
      16-fold higher in psoriatic scales than in normal epidermis (3.2+/-2.3 and < 0.2
      ng per mg, respectively), whereas hepoxilin A3 was not detected in any sample.
      Trioxilins were semiquantitated and referred to 12-hydroxyeicosatetraenoic acid,
      ratios of trioxilins A3 and B3 12-hydroxyeicosatetraenoic acid in psoriatic
      lesions were 0.65+/-0.23 and 0.32+/-0.28, respectively, and they were not
      detected in normal epidermis. The presence of a great amount of trioxilin A3
      strongly suggests that hepoxilin A3 was present in psoriatic lesions and it was
      totally degraded to trioxilin A3 during the analysis procedure. Our results
      demonstrate that hepoxilins and trioxilins are produced by human skin in vivo and
      that the levels of these compounds are increased in psoriasis. The reported
      biologic activities of hepoxilins indicate that they could amplify and maintain
      the inflammatory response. Our results reinforce the idea that these compounds
      could play a role as mediators in the inflammatory response in skin, particularly
      in psoriasis.

PMID- 9540967
TI  - Psoriasis: A possible reservoir for human papillomavirus type 5, the virus
      associated with skin carcinomas of epidermodysplasia verruciformis.
AB  - Recent polymerase chain reaction data have shown that most human papillomavirus
      (HPV) genotypes associated with epidermodysplasia verruciformis (EV) are
      widespread; however, HPV5 associated with EV skin carcinomas has only rarely been
      detected in non-EV patients. To identify the reservoir of this virus, we examined
      335 sera from different groups of patients for the presence of HPV5 antibodies by
      an enzyme-linked immunosorbent assay test based on HPV5 virus-like particles. The
      prevalence of antibodies reacting with HPV5 virus-like particles was found to be
      significantly higher in psoriatic patients (24.5%) than in other groups (2-5%),
      including patients with atopic dermatitis and renal transplant recipients.
      Analysis of scrapings of lesional and uninvolved skin by a nested polymerase
      chain reaction method, using degenerate EV HPV primers, disclosed HPV DNA in
      91.7% of 48 psoriatic skin samples and 35.5% of 31 atopic dermatitis specimens.
      Eleven EV HPV genotypes, most frequently HPV5 and HPV36, and a putative novel
      genotype (PsoX1) were identified in psoriasis. Five EV HPV genotypes and two
      putative novel genotypes (ADX1 and ADX2) were detected in atopic dermatitis
      patients. HPV5 was not found in atopic dermatitis patients. Using type specific
      primers, HPV5, HPV36, and HPV1 were found in 89.4%, 84.2%, and 42.1% of specimens
      from psoriatic patients, whereas HPV36 was detected in 22.5% of specimens from
      atopic dermatitis patients. HPV16 was never detected. On the whole, 27 HPV5 and
      13 HPV36 DNA variants were disclosed after sequencing amplification products. Our
      data confirm that EV HPV are widespread and point to psoriasis as a reservoir for
      HPV5. Whether HPV5 is involved in the pathogenesis of psoriasis remains to be
      determined.

PMID- 9540968
TI  - A potential role for ceramide in the regulation of mouse epidermal keratinocyte
      proliferation and differentiation.
AB  - We have previously determined that sustained phospholipase D (PLD) activation is
      associated with differentiation induction in primary mouse epidermal
      keratinocytes. We therefore investigated the effect of two bacterial PLD on
      keratinocyte proliferation and differentiation. We found that Streptomyces sp.
      PLD was much less potent at inhibiting proliferation than S. chromofuscus PLD,
      with a half-maximal inhibitory concentration of 0.05 versus less than 0.001 IU
      per ml for S. chromofuscus PLD. Similarly, S. chromofuscus PLD stimulated
      transglutaminase activity more effectively and potently than S. sp. PLD. When we
      examined the formation of products by the two PLD, we found that the S. sp. PLD
      showed higher activity at all concentrations. Whereas the PLD from S. sp. is
      relatively inactive on sphingomyelin, S. chromofuscus PLD is known to hydrolyze
      both glycerophospholipids and sphingomyelin. Based on recent data indicating a
      role for ceramide in regulating cell growth and differentiation, we hypothesized
      that the ability of S. chromofuscus PLD to hydrolyze sphingomyelin might underlie
      its greater potency. Therefore, we examined the effect of exogenous
      sphingomyelinase and synthetic ceramides on DNA synthesis. We found that
      sphingomyelinase exhibited a potent concentration-dependent effect on
      [3H]thymidine incorporation, much like S. chromofuscus PLD. Synthetic cell
      permeable ceramides (C6- and C2-ceramide) also concentration dependently
      inhibited DNA synthesis, with a half-maximal inhibitory concentration of
      approximately 12 microM. Finally, we obtained evidence suggesting that ceramide
      is generated in response to a physiologically relevant agent, because tumor
      necrosis factor-alpha, a known effector of sphingomyelin turnover in other
      systems and a cytokine that is produced and released by keratinocytes, increased
      ceramide levels in primary epidermal keratinocytes.

PMID- 9540970
TI  - Effects of [D-Ala1] peptide T-NH2 and HIV envelope glycoprotein gp120 on cyclic
      AMP dependent protein kinases in normal and psoriatic human fibroblasts.
AB  - In addition to acquired immunodeficiency syndrome (AIDS), persons infected with
      human immunodeficiency virus often develop cutaneous manifestations, including
      severe psoriasis. In previous studies, we have established that psoriatic
      fibroblasts and erythrocytes obtained from psoriatic patients exhibit decreased
      levels of cyclic adenosine monophosphate (cAMP) dependent protein kinase (PKA)
      activity and of 8-azido-[32P]cAMP binding to the RI and RII regulatory subunits
      of PKA. Because treatment of patients with peptide T (an octapeptide sequence
      found in the human immunodeficiency virus envelope glycoprotein gp120) has been
      observed to result in an improvement in the psoriatic condition, studies were
      initiated to determine if peptide T and gp120 protein treatment of normal and
      psoriatic human fibroblasts resulted in any changes in PKA. Exposure of psoriatic
      fibroblasts to peptide T resulted in a time (4 h to 6 d) and dose [10(-14)-10(-8)
      M] dependent increase in the levels of 8-azido-[32P]cAMP binding to the RI and
      RII regulatory subunits of PKA, along with a corresponding increase in PKA
      activity. Peptide T exhibited a biphasic dose dependent response, with maximal
      effects on PKA noted at 10(-12)M peptide T. Treatment of normal human fibroblasts
      with peptide T did not result in any change in PKA levels. Conversely, treatment
      of normal human fibroblasts for 18 h with gp120 protein [10(-13) M] resulted in a
      significant decrease in the levels of 8-azido-[32P]cAMP binding to RI and RII and
      in PKA activity. The presence of peptide T blocked this effect of the gp120
      protein. These results indicate that peptide T and gp120 protein may inversely
      alter the intracellular levels of 8-azido-[32P]cAMP binding to RI and RII, and of
      PKA activity in susceptible cells. These observed changes in the cyclic AMP-PKA
      signaling pathway, a biochemical marker for psoriasis, may offer some mechanistic
      insight into the noted beneficial effects of peptide T treatment, including an
      improvement in psoriatic lesions.

PMID- 9540969
TI  - The cytoplasmic tail of the mouse brown locus product determines intracellular
      stability and export from the endoplasmic reticulum.
AB  - Several melanosome membrane proteins have been identified, forming a family of
      proteins known as tyrosinase related proteins. Human TRP-1/gp75 is sorted to
      melanosomes through the endoplasmic reticulum and Golgi complex to the endocytic
      pathway, directed by a sorting signal located in the cytoplasmic tail. This
      hexapeptide cytoplasmic sequence, which is conserved in the tyrosinase related
      protein family and through vertebrate evolution, was shown to act also as a
      sorting signal in mouse gp75, confirming that its sorting and cellular retention
      function is conserved between human and mouse. The cytoplasmic tail influenced
      the rate and efficiency of intracellular transport of gp75 from the endoplasmic
      reticulum to the cis-Golgi. Deletion of 33 or 27 amino acids from the carboxyl
      end of the 38 amino acid cytoplasmic tail of gp75 caused retention and rapid
      degradation of the truncated gp75 in the endoplasmic reticulum. This defective
      movement could be fully corrected by extending the truncated tail with the
      unrelated cytoplasmic tail of the low density lipoprotein receptor. Thus, the
      cytoplasmic tail of mouse gp75 not only determines sorting to the
      endocytic/melanosomal compartment, but also controls export from the endoplasmic
      reticulum to Golgi.

PMID- 9540971
TI  - Local injection of hepatocyte growth factor/scatter factor (HGF/SF) alters cyclic
      growth of murine hair follicles.
AB  - Hepatocyte growth factor/scatter factor (HGF/SF) has recently been shown to
      stimulate the hair follicle growth of mouse vibrissae in vitro. In this study, we
      analyzed the effect of cutaneous injections of recombinant human HGF/SF on hair
      follicle growth using mice in different hair cycle stages. Five male newborn
      mice, five male mice in second anagen, and five male mice in second telogen were
      administered a dorsal intradermal injection of 1 microg HGF/SF dissolved in 0.1%
      albumin-phosphate-buffered saline once daily for five or seven consecutive days,
      and then sacrificed on days 7 or 10. Hair follicle growth was evaluated
      photometrically and histologically using three parameters: the skin color of the
      reverse side of the resected skin, the skin thickness, and the area occupied by
      hair follicle tissue. The HGF/SF injected skin of newborn mice had hair follicles
      that were histologically longer and larger than those of the 0.1% albumin
      phosphate-buffered saline injected skin. Mice that had received HGF/SF injection
      in second anagen, retained anagen hair follicles after 10 d only at the injection
      site, suggesting that HGF/SF delayed the transition from anagen to telogen. The
      HGF/SF injected skin of telogen mice had a significant increase in hair follicle
      tissue in the dermis, suggesting a mild anagen inducible activity by HGF/SF.
      Furthermore, precise measurements of the 20 hairs plucked from the HGF/SF
      injection sites revealed mild hair elongation in all the aforementioned
      experiments. These results imply that HGF/SF acts as a paracrine factor that
      alters cyclic hair growth of mice.

PMID- 9540973
TI  - Evaluation of the capacity of dendritic cells derived from cord blood CD34+
      precursors to present haptens to unsensitized autologous T cells in vitro.
AB  - Langerhans cells play a key role in contact hypersensitivity reactions. The
      application of haptens on the skin leads to many modifications of these cells,
      including the increase of major histocompatibility complex II expression,
      allogeneic stimulation potency, and migration towards lymph nodes to activate T
      cells. Moreover, it has been shown that Langerhans cells cultured in vitro are
      able to prime naive T cells in response to hapten contact. From CD34+ progenitors
      present in cord blood, we generated dendritic cells of which some presented the
      phenotypic markers of Langerhans cells. We show that these cells are able to
      sensitize syngeneic naive (CD45RA+) T cells to haptens such as trinitrophenyl
      conjugate of trinitrobenzene sulfonic acid (TNP) and fluoroscein isothiocyanate.
      The response to TNP is higher than to fluoroscein isothiocyanate, whereas sodium
      dodecyl sulfate, an irritant molecule used as a control, never caused this
      effect. Phenotypic analysis of cellular suspensions and experiments of cell
      sorting lead to the conclusion that only CD1a+ cells are able to induce a primary
      response of syngeneic T cells to TNP or fluoroscein isothiocyanate. Furthermore,
      we have shown a close relationship between the differentiation state of dendritic
      cells and their ability to prime T lymphocytes. Dendritic cells are able to
      present haptens in an efficient manner between day 10 and 14 of culturing CD34+
      progenitors, whereas they were efficient in presenting alloantigens from day 6
      until after day 20. This dissociation suggests the need of an active metabolic
      process for hapten presentation in the direct treatment of dendritic cells with
      haptens. This model of hapten presentation was used for a panel of fragrance
      molecules and other molecules considered as weaker haptens than TNP and
      fluoroscein isothiocyanate.

PMID- 9540972
TI  - A novel in vivo model for evaluating agents that protect against ultraviolet A
      induced photoaging.
AB  - Increasing evidence demonstrates that ultraviolet A radiation (UVA) contributes
      to photoaging, which results in the accumulation of massive amounts of abnormal
      elastic material in the dermis of photoaged skin. To study UVA-induced photoaging
      in an in vivo system, we utilized a line of transgenic mice containing the human
      elastin promoter linked to a chloramphenicol acetyl transferase reporter gene.
      Our prior work demonstrates promoter activation in response to ultraviolet B
      radiation (UVB), UVA, and psoralen plus ultraviolet A radiation in the skin of
      these mice. The addition of psoralen (8-MOP) prior to administration of UVA
      results in substantial increases in promoter activation, as compared with UVA
      alone. To demonstrate the utility of these mice as a model of UVA-induced
      photodamage, we administered four lotions to the skin of our transgenic mice that
      included: a sunscreen containing octyl methoxycinnamate and benzophenone-3 with a
      sun protection factor (SPF) of 15, the UVA filter butyl methoxydibenzoylmethane,
      the SPF 15 sunscreen and the UVA filter together, and the lotion vehicle alone.
      Following sunscreen administration, mice received a single psoralen plus
      ultraviolet A radiation treatment. All sunscreens decreased chloramphenicol
      acetyl transferase activity with the SPF 15 sunscreen, the UVA filter, and the
      combination SPF 15 sunscreen and UVA filter, resulting in increasing degrees of
      protection against psoralen plus ultraviolet A radiation. These results
      demonstrate that this model functions as a rapid and sensitive model of UVA
      photodamage for the identification and comparison of compounds that protect
      against UVA-induced photoaging.

PMID- 9540974
TI  - Post-transcriptional regulation of UV induced TNF-alpha expression.
AB  - Ultraviolet (UV) irradiation exerts multiple effects on skin cells, including the
      induction of several cytokines involved in immunomodulation. Specifically, UV
      irradiation has been shown to upregulate the level of tumor necrosis factor-alpha
      (TNF-alpha) mRNA in keratinocytes. To determine whether the induction of TNF
      alpha mRNA is regulated by transcriptional or post-transcriptional mechanisms, we
      examined cells of keratinocytic lineage (SCC12F) for steady state level,
      transcription rate, and stability of TNF-alpha mRNA after UV irradiation. Within
      4 h there was a 20-40-fold induction of TNF-alpha mRNA that persisted at lower
      levels through 48 h. Consistently, TNF-alpha protein secretion increased at 24
      and 48 h after UV irradiation. UV irradiation increased the half-life of TNF
      alpha mRNA from approximately 35 min to approximately 10 h. Conversely, the
      transcription rate of the TNF-alpha gene increased < 2-fold at the time of peak
      mRNA steady state levels. Thus, post-transcriptional mechanisms play a major role
      in UV induced TNF-alpha transcript level.

PMID- 9540975
TI  - Differential effects of detergents on keratinocyte gene expression.
AB  - We have studied the effect of various detergents on keratinocyte gene expression
      in vitro, using an anionic detergent (sodium dodecyl sulfate), a cationic
      detergent cetyltrimethylammoniumbromide (CTAB), and two nonionic detergents,
      Nonidet P-40 and Tween-20. We measured the effect of these detergents on direct
      cellular toxicity (lactate dehydrogenase release), on the expression of markers
      for normal differentiation (cytokeratin 1 and involucrin expression), and on
      disturbed keratinocyte differentiation (SKALP) by northern blot analysis. As
      reported in other studies, large differences were noted in direct cellular
      toxicity. In a culture model that mimics normal epidermal differentiation we
      found that low concentrations of sodium dodecyl sulfate could induce the
      expression of SKALP, a proteinase inhibitor that is not normally expressed in
      human epidermis but is found in hyperproliferative skin. Sodium dodecyl sulfate
      caused upregulation of involucrin and downregulation of cytokeratin 1 expression,
      which is associated with the hyperproliferative/inflammatory epidermal phenotype
      found in psoriasis, wound healing, and skin irritation. These changes were not
      induced after treatment of cultures with CTAB, Triton X-100, and Nonidet-P40.
      This effect appeared to be specific for the class of anionic detergents because
      sodium dodecyl benzene sulfonate and sodium laurate also induced SKALP
      expression. These in vitro findings showed only a partial correlation with the
      potential of different detergents to induce clinical, biophysical, and cell
      biologic changes in vivo in human skin. Both sodium dodecyl sulfate and CTAB were
      found to cause induction and upregulation of SKALP and involucrin at low doses
      following a 24 h patch test, whereas high concentrations of Triton X-100 did not.
      Sodium dodecyl sulfate induced higher rates of transepidermal water loss, whereas
      CTAB treated skin showed more signs of cellular toxicity. We conclude that the
      action of anionic detergents on epidermal keratinocytes is qualitatively
      different from the other detergents tested, which might have implications for in
      vitro toxicology studies that use cell biologic parameters as a read-out. We
      would hypothesize that detergents cause skin injury by several mechanisms that
      include direct cellular toxicity, disruption of barrier function, and detergent
      specific effects on cellular differentiation, as demonstrated here for sodium
      dodecyl sulfate, sodium dodecyl benzene sulfonate, and sodium laurate.

PMID- 9540976
TI  - Quantification of tyrosinase, TRP-1, and Trp-2 transcripts in human melanocytes
      by reverse transcriptase-competitive multiplex PCR--regulation by steroid
      hormones.
AB  - We have introduced a reverse transcriptase polymerase chain reaction based method
      to measure mRNA levels of the melanogenesis enzymes tyrosinase, tyrosinase
      related-protein 1 (TRP-1), and tyrosinase-related-protein 2 (TRP-2). Expression
      was determined by reverse transcriptase-competitive multiplex polymerase chain
      reaction of (i) melanogenesis enzyme transcripts and the "housekeeping" gene
      glyceraldehyde-3-phosphate dehydrogenase, and (ii) two internal standards
      consisting of mutated melanogenesis enzyme cDNA and mutated gene glyceraldehyde-3
      phosphate dehydrogenase cDNA. This was investigated on in vitro cultured
      melanocytes in the presence of three different steroids; one glucocorticoid
      (betamethasone-17-valerate) and two sex steroids (diethylstilbestrol and
      estradiol). All three steroids lead to an increase of about 1.5-2.5-fold of
      tyrosinase transcripts. The amount of TRP-1 transcripts was likewise enhanced,
      but only moderately (approximately 1.5-fold). In contrast, TRP-2 transcripts were
      reduced by approximately 40% in number after betamethasone-17-valerate treatment,
      whereas the two sex steroids, diethylstilbestrol and estradiol, caused an
      upregulation of about 20-fold of the initial TRP-2 transcript level. We therefore
      suggest that hyperpigmentation during pregnancy or under contraceptive treatment
      is mediated by a direct induction of melanogenesis via sex steroids.

PMID- 9540977
TI  - Keratinocyte differentiation is stimulated by activators of the nuclear hormone
      receptor PPARalpha.
AB  - Peroxisome proliferator activated receptors (PPAR) belong to the superfamily of
      nuclear hormone receptors that heterodimerize with the retinoid X receptor and
      regulate transcription of several genes involved in lipid metabolism and
      adipocyte differentiation. Because of the role of 1,25-dihydroxyvitamin D3 and
      retinoic acid working through similar receptors (the vitamin D receptor and
      retinoic acid receptor, respectively) on keratinocyte differentiation, we have
      examined the effects of activators of PPARalpha on keratinocyte differentiation.
      The rate of cornified envelope formation was increased 3-fold in keratinocytes
      maintained in low calcium (0.03 mM) and incubated in the presence of clofibric
      acid, a potent PPARalpha activator. Involucrin, a cornified envelope precursor,
      and the cross-linking enzyme transglutaminase, were increased at both the message
      level (2-7-fold) and the protein level (4-12-fold) by clofibric acid.
      Furthermore, physiologic doses of the fatty acids oleic acid, linoleic acid, and
      eicosatetraynoic acid, which are also activators of PPARalpha, also induced
      involucrin and transglutaminase protein and mRNA. In contrast, the
      PPARgammaligand prostaglandin J2 had no effect on protein or mRNA levels of
      involucrin or transglutaminase. Levels of involucrin and transglutaminase mRNA
      and protein were induced by clofibric acid in keratinocytes incubated in 1.2 mM
      calcium, a concentration which by itself induces keratinocyte differentiation.
      Finally, PPARalpha activators inhibit DNA synthesis. This study demonstrates that
      PPARalpha activators, including putative endogenous ligands such as fatty acids,
      induce differentiation and inhibit proliferation in keratinocytes, and suggests a
      regulatory role for the PPARalpha in epidermal homeostasis.

PMID- 9540978
TI  - Decreased phospholipase D (PLD) activity in ceramide-induced apoptosis of human
      keratinocyte cell line HaCaT.
AB  - Ceramide is recognized as an intracellular lipid second messenger, which induces
      various kinds of cell function including apoptosis. To evaluate the competence of
      ceramide on the keratinocyte apoptosis, we examined effects of a cell-permeable
      ceramide, N-acetylsphingosine (C2-ceramide), on a human keratinocyte cell line,
      HaCaT. C2-ceramide induced a distinct apoptosis in HaCaT cells in a time
      dependent manner, as inferred by morphologic hallmarks of apoptosis such as bleb
      formation, cell body shrinkage, nuclear chromatin condensation, and
      internucleosomal DNA fragmentation. In sharp contrast, an inactive C2-ceramide,
      dihydroC2-ceramide, which lacks the 4-5trans double bond, failed to induce the
      apoptosis. The apoptotic HaCaT cells induced by C2-ceramide showed a significant
      suppression of phospholipase D (PLD) activity, regardless of the presence or
      absence of guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS). This indicates that
      C2-ceramide inhibits both GTPgammaS dependent and GTPgammaS independent PLD. The
      membrane associated GTPgammaS dependent PLD activity was stimulated by
      recombinant adenosine diphosphate-ribosylation factor. The adenosine diphosphate
      ribosylation factor dependent and independent PLD activities were inhibited by C2
      ceramide in a concentration dependent manner, but not by the inactive C2
      ceramide. The concentration of C2-ceramide to inhibit the membrane associated PLD
      activity was comparable with that required for apoptosis induction in HaCaT
      cells. It was thus suggested that downregulation of PLD activity may be involved
      in the mechanism underlying C2-ceramide induced keratinocyte apoptosis.

PMID- 9540979
TI  - Glucosylceramides stimulate mitogenesis in aged murine epidermis.
AB  - Glucosylceramides (GlcCer) and ceramides (Cer) appear to have opposite effects on
      epidermal growth and differentiation. Whereas Cer inhibit mitosis and induce
      terminal differentiation and apoptosis in cultured keratinocytes, GlcCer is
      mitogenic in young murine epidermis. Using a recently described murine model of
      chronologic senescence we explored whether GlcCer is mitogenic in aged epidermis.
      Epidermal GlcCer content increases following topical applications of either
      conduritol-B epoxide (CBE), an inhibitor of GlcCer hydrolysis, or exogenous
      GlcCer in a penetration-enhancing vehicle. During chronologic aging in the
      hairless mouse, baseline epidermal DNA synthesis rates remain normal until 18 mo,
      but decline significantly at 24 mo. Topical CBE stimulates a 1.5- to 1.9-fold
      increase in epidermal DNA synthesis in all age groups (i.e., 1-2, 18, and 24 mo).
      Although the CBE induced increase in [3H]thymidine incorporation in 24 mo old
      animals is significant (p < 0.01), it is not sufficient to reach the absolute
      levels reached in similarly treated, younger mouse epidermis. Moreover, topical
      GlcCer induced mitogenesis is both dose dependent and hexose specific in young (1
      2 mo old) animals, and remains effective in aged (< or = 24 mo old) animals.
      Furthermore, the CBE induced increase in DNA synthesis in aged epidermis is
      sufficient to produce epidermal hyperplasia. Finally, although an increased
      GlcCer:Cer ratio can alter stratum corneum barrier function and membrane
      structure, neither stratum corneum function nor extracellular membrane structure
      change under these experimental conditions, and therefore the mitogenic effects
      of increased epidermal GlcCer cannot be attributed to effects on the stratum
      corneum. These results show that: (i) elevations in endogenous GlcCer are
      mitogenic for aged as well as young murine epidermis; (ii) topical GlcCer is also
      mitogenic when delivered in an enhancing vehicle; and (iii) despite the putative
      importance of epidermal DNA synthesis for barrier homeostasis, these mitogenic
      alterations do not alter stratum corneum function.

PMID- 9540980
TI  - Heterogeneous MHC II restriction pattern of autoreactive desmoglein 3 specific T
      cell responses in pemphigus vulgaris patients and normals.
AB  - Pemphigus vulgaris is a life threatening bullous autoimmune disease of the skin
      mediated by autoantibodies against desmoglein 3 (Dsg3) on epidermal
      keratinocytes. Pemphigus vulgaris patients exhibit T cell responses against Dsg3
      that may serve as a target to modulate the production of pathogenic
      autoantibodies. Healthy carriers of major histocompatibility complex class II
      alleles identical or similar to those that are highly prevalent in pemphigus
      vulgaris, namely DRbeta1*0402 and DRbeta1*1401, also mount T cell responses
      against Dsg3. We thus wanted to determine whether these prevalent major
      histocompatibility complex class II alleles restricted Dsg3 specific T cell
      responses. A CD4+ T cell line from the DRbeta1*0402+ patient PV9 was stimulated
      by Dsg3 with DRbeta1*0402+ L cells as antigen-presenting cells. A CD4+ T cell
      line and six CD4+ T cell clones from the DR11/14+ patient PV8, and six CD4+ T
      cell clones from the DR11+ healthy donor C6, required DR11/ DQbeta1*0301+
      peripheral blood mononuclear cells but not DR11+ L cells as antigen-presenting
      cells and were strongly inhibited by anti-DQ antibodies, indicating that they
      were restricted by HLA-DQbeta1*0301. A CD4+ T cell line and three T cell clones
      from the DR11+ healthy donor C11 were differentially stimulated by Dsg3 with L
      cells expressing one of several DR11 alleles. T cell recognition of Dsg3 was thus
      not only restricted by the pemphigus vulgaris associated DRbeta1*0402 allele, but
      also by several DR11 alleles, some of which are highly homologous to
      DRbeta1*0402, and by HLA-DQbeta1*0301.

PMID- 9540981
TI  - Structure of water, proteins, and lipids in intact human skin, hair, and nail.
AB  - Raman spectroscopy is a nondestructive analytical method for determining the
      structure and conformation of molecular compounds. It does not require sample
      preparation or pretreatment. Recently, near-infrared Fourier transform Raman
      spectroscopy has emerged as being specially suited for investigations of biologic
      material. In this study, we obtained near-infrared Fourier transform Raman
      spectra of intact human skin, hair, nail, and stratum corneum. We disclosed major
      spectral differences in conformational behavior of lipids and proteins between
      normal skin, hair, and nail. The amide I and III band location indicated that the
      majority of proteins in all samples have the same secondary alpha-helix
      structure. Positions of (S-S) stretching bands of proteins revealed a higher
      stability of the disulfide bonds in the hair and the nail. Analysis of vibrations
      of protein -CH groups showed that in the hair and the nail the proteins are
      apparently highly folded, interacting with the surroundings only to a small
      degree. The position of lipid specific peaks in spectra of hair, nail, and
      stratum corneum suggested a highly ordered, lamellar crystalline lipid structure.
      A greater lipid fluidity was found in whole skin. Assessment of the structure of
      water clusters revealed that mainly bound water is present in the human skin,
      stratum corneum, and nail. In conclusion, structural changes of water, proteins,
      and lipids in intact skin and skin appendages may be analyzed by Raman
      spectroscopy. This technique may be used in the future in a noninvasive analysis
      of structural changes in molecular compounds in the skin, hair, and nail
      associated with different dermatologic diseases.

PMID- 9540982
TI  - Formation of the epidermal calcium gradient coincides with key milestones of
      barrier ontogenesis in the rodent.
AB  - The epidermal permeability barrier forms late in gestation, coincident with
      decreased lipid synthesis, increased lipid processing, and development of a
      mature, multi-layered stratum corneum. Prior studies have shown that changes in
      the epidermal Ca++ gradient in vivo regulate lamellar body secretion and lipid
      synthesis, and modulations in extracellular Ca++ in vitro also regulate
      keratinocyte differentiation. We asked here whether a Ca++ gradient forms in
      fetal epidermis in utero, and whether its emergence correlates with key
      developmental milestones of barrier formation and stratum corneum development.
      Using either ion precipitation or proton induced X-ray emission analysis of fetal
      mouse and rat skin, we showed that a Ca++ gradient is not present at gestational
      days 16-18, prior to barrier formation, and that a gradient forms coincident with
      the emergence of barrier competence (day 19, mouse; day 20, rat) prior to birth.
      These results are consistent with a role for Ca++ in the regulation of key
      metabolic events leading to barrier formation. Whether the calcium gradient is
      formed actively or passively remains to be determined.

PMID- 9540983
TI  - Defective global genome repair in XPC mice is associated with skin cancer
      susceptibility but not with sensitivity to UVB induced erythema and edema.
AB  - It is generally presumed that xeroderma pigmentosum (XP) patients are extremely
      sensitive to developing UV erythema, and that they have a more than 1000-fold
      increased skin cancer risk. Recently established mouse models for XP can be
      employed to investigate the mechanism of these increased susceptibilities. In
      line with human data, both XPA and XPC knockout mice have been shown to have an
      increased susceptibility to UVB induced squamous cell carcinomas. In XPA
      knockouts, nucleotide excision repair of UV induced DNA photolesions is
      completely defective (i.e., both global genome repair and transcription coupled
      repair are defective). We determined the strand specific removal of cyclobutane
      pyrimidine dimers and pyrimidine [6-4] pyrimidone photoproducts from the p53 gene
      in cells from XPC knockout mice and wild-type littermates. Analogous to human XPC
      cells, embryonic fibroblasts from XPC knockout mice are only capable of
      performing transcription coupled repair of DNA photolesions. We show that these
      XPC knockout mice, in striking contrast to XPA knockout mice, do not have a lower
      minimal erythema/edema dose than their wild-type littermates. Hence, defective
      global genome repair appears to lead to skin cancer susceptibility, but does not
      influence the sensitivity to acute effects of UVB radiation, such as erythema and
      edema. The latter phenomena thus relate to the capacity to perform transcription
      coupled repair, which suggests that blockage of RNA synthesis is a key event in
      the development of UV erythema and edema.

PMID- 9540984
TI  - The effects of inflammatory cytokines on the isolated human sebaceous
      infundibulum.
AB  - The human sebaceous pilosebaceous infundibulum was isolated and maintained in
      medium for up to 7 d. Freshly isolated infundibula were found to express keratins
      1, 5, 6, 16, and 17, as determined by immunohistochemistry. In addition, freshly
      isolated infundibula expressed filaggrin, profilaggrin, involucrin, cornifin
      alpha, and loricrin. This pattern of expression was retained over 7 d. The
      addition of 100 U interferon (IFN)-gamma per ml over 3 d and 1 nM phorbol
      myristate acetate over 24 h resulted in the expression of intercellular adhesion
      molecule (ICAM)-1 and HLA-DR by infundibular keratinocytes, as determined by
      immunohistochemistry. Ten nanograms tumor necrosis factor-alpha per ml and 10 ng
      IL-6 per ml both caused expression of ICAM-1 alone. IL-1alpha had no effect on
      the expression of ICAM-1 or HLA-DR over 3 d, but addition of 1 ng IL-1alpha per
      ml over 7 d in culture resulted in hypercornification of the keratinocytes of the
      infundibulum, apparently brought about by early keratinocyte cornification. These
      data suggest that the isolated, maintained, infundibulum is a good model for
      studying the effects of inflammatory cytokines on the infundibulum, and that IL
      1alpha acts on infundibular keratinocytes to promote cornification.

PMID- 9540985
TI  - Activation of tissue inhibitor of metalloproteinases-3 (TIMP-3) mRNA expression
      in scleroderma skin fibroblasts.
AB  - Excessive accumulation of fibrillar collagens is a hallmark of the cutaneous
      fibrosis in both systemic and localized scleroderma. Turnover of the collagenous
      extracellular matrix is dependent on the balance between collagenolytic matrix
      metalloproteinases and their specific inhibitors. We have examined the expression
      of the novel, matrix associated tissue inhibitor of metalloproteinases-3 (TIMP-3)
      in normal and scleroderma skin fibroblasts in culture and in vivo. The levels of
      TIMP-3 mRNA were elevated up to 2.5-fold in five of seven systemic sclerosis
      fibroblast strains, whereas TIMP-1 mRNA expression was elevated up to 1.8-fold in
      two and TIMP-2 mRNA expression up to 1.8-fold in two systemic sclerosis strains.
      Using in situ hybridization, TIMP-3 mRNA was detected in seven of 12 localized
      scleroderma skin samples, specifically in fibroblasts within fibrotic collagen
      fibers or in the vicinity of inflammatory cells. TIMP-1 mRNA was detected in
      three of eight scleroderma skin samples in fibroblasts adjacent to inflammatory
      cells. The expression of TIMP-3 mRNA by systemic sclerosis and normal skin
      fibroblasts was enhanced to a similar extent (by 8.6- and 8.1-fold, respectively)
      by transforming growth factor-beta, and suppressed down to 34 and 54%,
      respectively, by tumor necrosis factor-alpha. Specific activation of TIMP-3 gene
      expression in scleroderma skin fibroblasts in culture and in vivo suggests a role
      for TIMP-3 in the pathogenesis of dermal fibrosis via inhibition of turnover of
      fibrotic dermal extracellular matrix, possibly due to upregulation of TIMP-3
      expression by transforming growth factor-beta.

PMID- 9540986
TI  - The human hair follicle: a reservoir of CD40+ B7-deficient Langerhans cells that
      repopulate epidermis after UVB exposure.
AB  - The ability of skin to maintain its protective structural and functional
      integrity depends on both resident and circulating cells. Until now, it was
      thought that dendritic antigen presenting cells of epidermis (Langerhans cells)
      were replaced by circulating bone marrow derived precursors. Here we show by
      immunostaining studies of timed biopsies taken from human skin after ultraviolet
      exposure, that hair follicle is a critical reservoir of Langerhans cells that
      repopulate epidermis depleted of Langerhans cells by a single four minimal
      erythema dose of ultraviolet B. Immunostaining with antibodies to thymidine
      dimers showed that ultraviolet B only penetrated the superficial hair follicle
      opening, whereas deeper follicle was relatively protected. Langerhans cells
      migrating from hair follicle into epidermis 72 h after ultraviolet exposure have
      a partial deficiency of molecules important to T cell costimulation. We used four
      color flow cytometry to show that Langerhans cells isolated from epidermis 72 h
      after ultraviolet B can upregulate CD40 but not B7-1 or B7-2 expression in
      culture, suggesting a different phenotype of hair follicle Langerhans cells.
      Therefore, the hair follicle is a specialized immune compartment of the skin that
      serves as an intermediate reservoir of Langerhans cells between bone marrow and
      epidermis, and that may play a critical role in immune surveillance.

PMID- 9540987
TI  - Aliphatic and alicyclic diols induce melanogenesis in cultured cells and guinea
      pig skin.
AB  - We have found that several aliphatic and alicyclic diols induce melanogenesis in
      cultured S91 mouse melanoma cells and normal human epidermal melanocytes (NHEM).
      In addition, these compounds induce melanogenesis when applied to guinea pig
      skin, with transfer of melanin to keratinocytes and formation of "supranuclear
      caps," as occurs in naturally pigmented skin. The relative order of potency of
      some of these diols in NHEM is 5-norbornene-2,2-dimethanol > 3,3-dimethyl-1,2
      butanediol > cis-1,2-cyclopentanediol > 2,3-dimethyl-2,3-butanediol > 1,2
      propanediol. Following treatment with these diols or 3-isobutyl-1-methylxanthine,
      melanin and tyrosinase activity are increased within S91 cells and NHEM; however,
      for cultured NHEM, the largest increases of melanin and tyrosinase occur in an
      extracellular particulate fraction, shown by electron microscopy to consist
      almost entirely of stage III and IV melanosomes. These results indicate that
      cultured NHEM treated with diols export melanosomes in a fashion that is
      commensurate with natural melanogenic processes. In contrast, S91 mouse melanoma
      cells exhibit aberrant melanosomal trafficking, in accordance with the known
      defect in myosin-V mediated melanosomal transport. Both S91 cells and NHEM
      exhibit morphologic changes and growth arrest indicative of differentiation
      following treatment with diols. The diols described in this report are candidates
      for use as cosmeceutical tanning agents.

PMID- 9540988
TI  - Cutaneous tumors in patients with multiple endocrine neoplasia type 1 show
      allelic deletion of the MEN1 gene.
AB  - Multiple endocrine neoplasia type 1 (MEN1), the heritable tendency to develop
      tumors of the parathyroid, pituitary, and entero-pancreatic endocrine tissues, is
      the consequence of a germline mutation in the MEN1 gene. Endocrine tumors in
      these patients result when the mutant MEN1 allele is accompanied by loss of the
      normal MEN1 allele. Recently it was reported that MEN1 patients also exhibit
      several cutaneous tumors, including multiple angiofibromas, collagenomas, and
      lipomas. The purpose of this study was to examine skin lesions from patients with
      MEN1 for allelic loss of the MEN1 gene. Skin lesions from five patients with MEN1
      were examined using fluorescence in situ hybridization. Six angiofibromas, three
      collagenomas, and one lipoma showed allelic deletion of the MEN1 gene. Allelic
      deletion was not observed in a melanocytic nevus or acrochordon from patients
      with MEN1. It was also not observed in an angiofibroma from a patient with
      tuberous sclerosis. These results suggest that loss of function of the wild-type
      MEN1 gene product plays a role in the development of angiofibromas, collagenomas,
      and lipomas in patients with MEN1.

PMID- 9540989
TI  - Entry into afferent lymphatics and maturation in situ of migrating murine
      cutaneous dendritic cells.
AB  - An important property of dendritic cells (DC), which contributes crucially to
      their strong immunogenic function, is their capacity to migrate from sites of
      antigen capture to the draining lymphoid organs. Here we studied in detail the
      migratory pathway and the differentiation of DC during migration in a skin organ
      culture model and, for comparison, in the conventional contact hypersensitivity
      system. We report several observations on the capacity of cutaneous DC to migrate
      in mouse ear skin. (i) Upon application of contact allergens in vivo the density
      of Langerhans cells in epidermal sheets decreased, as determined by
      immunostaining for major histocompatibility complex class II, ADPase, F4/80,
      CD11b, CD32, NLDC-145/DEC-205, and the cytoskeleton protein vimentin. Evaluation
      was performed by computer assisted morphometry. (ii) Chemically related
      nonsensitizing or tolerizing compounds left the density of Langerhans cells
      unchanged. (iii) Immunohistochemical double-staining of dermal sheets from skin
      organ cultures for major histocompatibility complex class II and CD54 excluded
      blood vessels as a cutaneous pathway of DC migration. (iv) Electron microscopy of
      organ cultures revealed dermal accumulations of DC (including Birbeck granule
      containing Langerhans cells) within typical lymphatic vessels. (v) Populations of
      migrating DC in organ cultures upregulated markers of maturity (the antigen
      recognized by monoclonal antibody 2A1, CD86), but retained indicators of
      immaturity (invariant chain, residual antigen processing function). These data
      provide additional evidence that during both the induction of contact
      hypersensitivity and in skin organ culture, Langerhans cells physically leave the
      epidermis. Both Langerhans cells and dermal DC enter lymphatic vessels. DC mature
      while they migrate through the skin.

PMID- 9540990
TI  - Variegate porphyria: identification of a nonsense mutation in the
      protoporphyrinogen oxidase gene.
AB  - The porphyrias are disorders of porphyrin metabolism that result from inherited
      or acquired aberrations in the control of the heme biosynthetic pathway.
      Variegate porphyria is characterized by a partial reduction in the activity of
      protoporphyrinogen oxidase. In this study, we identified the first nonsense
      mutation in a family with variegate porphyria. The mutation consisted of a
      previously unreported G-to-T transversion in exon 5 of the protoporphyrinogen
      oxidase gene, resulting in the substitution of glutamic acid by a nonsense codon,
      designated E133X. Our investigation establishes that a nonsense mutation in the
      protoporphyrinogen oxidase gene is the underlying mutation in this family with
      variegate porphyria.

PMID- 9540992
TI  - Adrenocorticotropic hormone (ACTH) but not alpha-melanocyte stimulating hormone
      (alpha-MSH) as a mediator of adrenalectomy induced hair growth in mink.

PMID- 9540991
TI  - Homozygous variegate porphyria: identification of mutations on both alleles of
      the protoporphyrinogen oxidase gene in a severely affected proband.
AB  - Homozygous variegate porphyria is a severe skin and neurologic disease
      manifesting in early infancy, and characterized by markedly reduced levels of the
      penultimate enzyme in the heme biosynthetic pathway, protoporphyrinogen oxidase.
      We investigated the molecular basis of variegate porphyria, usually an autosomal
      dominantly inherited trait, in a severely affected female proband and her
      parents. The mutation detection strategy included heteroduplex analysis,
      automated sequencing, and allele specific oligonucleotide hybridization. We
      identified two underlying missense mutations in the protoporphyrinogen oxidase
      gene, consisting of a G-to-A transition in exon 6 (G169E), and a G-to-A
      transition in exon 10 (G358R). Our study establishes the molecular basis of
      "homozygous" variegate porphyria for the first time, in demonstrating that this
      patient is a compound heterozygote for two different missense mutations in the
      protoporphyrinogen oxidase gene.

PMID- 9540993
TI  - Inhibition of chemotherapy-induced keratinocyte apoptosis in vivo by an
      interleukin-15-IgG fusion protein.

PMID- 9540994
TI  - Superantigens, autoantigens, and pathogenic T cells in psoriasis.

PMID- 9540995
TI  - Gene therapy for genetic skin disease.

PMID- 9540996
TI  - Identification of communication networks in Spo0F: a model for phosphorylation
      induced conformational change and implications for activation of multiple domain
      bacterial response regulators.
AB  - Fundamental to understanding the mechanism by which phosphorylation activates
      bacterial signal transduction response regulator proteins is the identification
      of regions and residues that are responsible for the phosphorylation-induced
      conformational change. Here we review results from structural and protein
      dynamics investigations, and combine them with mutagenesis studies on the
      response regulator protein SpoOF to suggest a model in which a network of buried
      and surface residues link surface regions required for protein:protein
      interactions to the site of phosphorylation. The network described for SpoOF may
      provide pathways through which information is transmitted from the site of
      phosphorylation, propagating a conformational change many angstroms away. The
      general applicability of the communication network model for all bacterial
      response regulator proteins is discussed.

PMID- 9540997
TI  - Identification and characterization of a novel member of the dystrobrevin gene
      family.
AB  - A new member of the dystrobrevin gene family was identified using a
      bioinformatics approach. Sequence analysis indicates that this gene, named DTN-B,
      is highly homologous to the rabbit A0, the previously described dystrobrevin
      (DTN), Torpedo 87 kDa and to the C-terminus of dystrophin. The coiled-coil
      domain, shown to be the site of interaction between dystrobrevins and dystrophin,
      is highly conserved. Immunostaining studies indicate that DTN-B and DTN
      expression is absent in affected muscle fibers from DMD patients and carriers.

PMID- 9540998
TI  - Diffusion-controlled DNA recognition by an unfolded, monomeric bZIP transcription
      factor.
AB  - Basic leucine zipper (bZIP) transcription factors are dimers that recognize
      mainly palindromic DNA sites. It has been assumed that bZIP factors have to form
      a dimer in order to bind to their target DNA. We find that DNA binding of both
      monomeric and dimeric bZIP transcription factor GCN4 is diffusion-limited and
      that, therefore, the rate of dimerization of the bZIP domain does not affect the
      rate of DNA recognition and GCN4 need not dimerize in order to bind to its
      specific DNA site. The results have implications for the mechanism by which bZIP
      transcription factors find their target sites for transcriptional regulation.

PMID- 9540999
TI  - Topological analysis of the ATP-gated ionotropic [correction of ionotrophic] P2X2
      receptor subunit.
AB  - We investigated the transmembrane topology of the P2X2 receptor subunit expressed
      in HEK 293 cells. Initial studies using two P2X subunits expressed in tandem
      indicated that the amino- and carboxy-termini are on the same side of the
      membrane. Immunofluorescence studies showed the cytoplasmic orientation of the
      amino- and carboxy-termini. Finally, N-glycosylation scanning mutagenesis
      revealed that reporter sites inserted into the central loop, but not those in the
      amino- or carboxy-terminal regions, were glycosylated, thus suggesting an
      extracellular placement for that domain. Our results support a two-transmembrane
      arrangement for P2X receptors with intracellular amino- and carboxy-termini.

PMID- 9541000
TI  - Differential expression of the protein kinase A regulatory subunit (RIalpha) in
      pancreatic endocrine cells.
AB  - A PCR-based subtractive cloning procedure was used to identify genes expressed at
      higher levels in the pancreatic beta cell line betaTC1, as compared to the
      pancreatic alpha cell line alphaTC1. One of the clones isolated by this procedure
      corresponded to the regulatory subunit (RIalpha) of protein kinase A (PKA). Using
      antibodies directed against RIalpha, we now demonstrate both by immunoblot and
      immunofluorescence that RIalpha protein is present at higher levels in cultured
      beta cells as compared to alpha cells. In vitro PKA assays revealed high basal
      PKA activity in alphaTC1 extracts, which changed little on addition of exogenous
      cAMP. On the other hand, extracts from beta cells showed very low basal activity
      of PKA, which was elevated upon addition of cAMP. A similar trend was observed in
      vivo using transfected luciferase constructs bearing multiple copies of a CRE
      element: in alphaTC1 cells, no induction by forskolin was observed, whereas in
      betaTC1 cells, forskolin produced a 9-fold increase in activity. Therefore, the
      results indicate that RIalpha of PKA is selectively expressed in pancreatic beta
      cells as compared to alpha cells: this selective expression is associated with
      major differences in the properties of the PKA signal transduction pathway.
      Differential expression of the regulatory subunit may play a role in determining
      the patterns of gene expression and signal transduction characteristic of alpha
      and beta cells.

PMID- 9541001
TI  - EcoRII endonuclease has two identical DNA-binding sites and cleaves one of two co
      ordinated recognition sites in one catalytic event.
AB  - EcoRII is a typical restriction enzyme that cleaves DNA using a two-site
      mechanism. EcoRII endonuclease is unable to cleave DNA which contains a small
      number of EcoRII recognition sites but the enzyme activity can be stimulated in
      the presence of DNA with a high frequency of EcoRII sites. To investigate the
      mechanism of activation, the kinetics of stimulated EcoRII cleavage has been
      studied. A 14 bp substrate activated the cleavage of the 71 bp substrate,
      containing one EcoRII recognition site (trans-activation) by a competitive
      mechanism: the activator increased substrate binding but not catalysis. The
      activation increased if the substrate concentration decreased and if the
      activator had a lower affinity for the enzyme than the substrate. The
      introduction of the second recognition site into the 71 bp duplex also enabled
      cleavage of this substrate (cis-activation). Pyrophosphate bonds were
      incorporated into one of two recognition sites to switch off the cleavage of the
      phosphodiester bonds. Analysis of cleavage products of these modified substrates
      showed that EcoRII cuts one of two coordinated recognition sites in one catalytic
      event.

PMID- 9541002
TI  - Elderberry (Sambucus nigra) contains truncated Neu5Ac(alpha-2,6)Gal/GalNAc
      binding type 2 ribosome-inactivating proteins.
AB  - Analysis of affinity-purified preparations of the fetuin-binding proteins from
      elderberry bark and fruits revealed besides the previously reported Neu5Ac(alpha
      2,6)Gal/GalNAc-specific type 2 ribosome-inactivating proteins (RIP) the
      occurrence of single chain proteins of 22 kDa, which according to their N
      terminal amino acid sequence correspond to the second part of the B chain of the
      respective type 2 RIP. Both proteins are very similar except that the
      polypeptides of the fruit lectin are 10 amino acid residues longer than these
      from the bark lectin. Our findings not only demonstrate the occurrence of
      carbohydrate-binding fragments of type 2 RIP but also provide further evidence
      that type 2 RIP genes give rise to complex mixtures of type 2 RIP/lectins in
      elderberry.

PMID- 9541004
TI  - Non-Watson-Crick base pairs modulate homologous alignments in RecA pairing
      reactions.
AB  - Complementary pairing by RecA was examined in vitro to investigate how homology
      is deciphered from non-homology. Somewhere in a window of 40-50% sequence
      complementarity, RecA pairing begins to manifest the specificity of homology.
      Quantitation reveals a hierarchy among non-Watson-Crick mispairs: RecA reaction
      treats six out of 12 possible mispairs as good ones and three each of the
      remaining ones as moderate and bad pairs. The mispairs seem to function as
      independent pairing units free of sequence context effects. The overall strength
      of pairing is simply the sum of the constituent units. RecA mediated gradation of
      mispairs, free of sequence context effects, might offer a general thumb-rule for
      predicting the pairing strength of any alignment that carries multiple mispairs.

PMID- 9541003
TI  - On the target of a novel class of antibiotics, oxazolidinones, active against
      multidrug-resistant Gram-positive bacteria.
AB  - Oxazolidinones are a promising new class of synthetic antibiotics active against
      multidrug-resistant Gram-positive bacteria. To elucidate their mode of action,
      the effect of DuP 721 on individual steps of protein translation was studied. The
      drug does not interfere with translation initiation at the stage of mRNA binding
      or formation of 30S pre-initiation complexes. However, it inhibits the puromycin
      mediated release of [35S]formyl-methionine from 70S initiation complexes in a
      dose-dependent manner. Inhibition involves binding of the oxazolidinone to the
      large ribosomal subunit and is twice as high with 50S subunits from Gram-positive
      as with those from Gram-negative bacteria.

PMID- 9541005
TI  - Nitric oxide (NO) disrupts specific DNA binding of the transcription factor c-Myb
      in vitro.
AB  - In an attempt to elucidate signal transduction pathways which may modulate DNA
      binding of the transcription factor c-Myb, we investigated whether c-Myb could be
      a target for the signaling molecule nitric oxide (NO) in vitro. NO-generating
      agents severely inhibited specific DNA binding of the c-Myb minimal DNA-binding
      domain R2R3. This inhibition was readily reversible upon treatment with excess
      DTT. A redox-sensitive cysteine (C130) was required for this NO sensitivity.
      Moreover, a DNA-binding domain carrying two of the avian myeloblastosis virus
      (AMV)-specific mutations (L106H, V117D) appeared to be less sensitive to S
      nitrosylation than the wild-type c-Myb. This difference in NO sensitivity may
      influence the regulation of wild type versus AMV v-Myb protein function.

PMID- 9541006
TI  - Differential scanning calorimetric studies of the glycoprotein, winged bean
      acidic lectin, isolated from the seeds of Psophocarpus tetrogonolobus.
AB  - Differential scanning calorimetry of solutions of WBAII and in presence of sugar
      ligands shows that WBAII dimer dissociates to its constituent monomeric subunits
      at the denaturation temperature. The thermal denaturation of WBAII consists of
      the unfolding of two independent domains of WBAII similar to that of basic winged
      bean lectin and ECorL and in contrast to concanavalin A (conA), pea and lentil
      lectin, which unfold as single entities. Apparently, the glycosylation reduces
      the structural integrity of WBAII as compared to conA, pea and lentil lectin. The
      increase in the denaturation temperature of the sugar-lectin complexes yields
      binding constants close to the binding constants extrapolated from the ITC
      results and confirms the mechanism proposed for its thermal unfolding.

PMID- 9541007
TI  - Inhibition of sphingolipid induced apoptosis by caspase inhibitors indicates that
      sphingosine acts in an earlier part of the apoptotic pathway than ceramide.
AB  - Caspases are specific proteases involved in apoptosis, and their inhibition by
      specific peptide inhibitors can inhibit apoptosis. With these inhibitors we
      examined the relationship of caspases and sphingolipids involved in the induction
      of apoptosis of human leukemic HL60 cells. We have previously shown that
      sphingosine (Sph) and its methylated derivative dimethylsphingosine (DMS)
      effectively induce apoptosis in HL60 cells. Using these lipids as well as
      ceramide analogues we found both similarities and differences in the caspase
      involvement in apoptosis induced by the two distinct lipid types. The wide
      spectrum caspase inhibitor Z-VAD-FMK and Z-DEVD-FMK, an inhibitor of the
      downstream caspases 3 (CPP32, Yama) and 7, both inhibited apoptosis induced by
      all the lipids tested. Z-AAD-FMK which inhibits the serine protease Granzyme B,
      inhibited Sph/DMS induced apoptosis, but little or no effect on ceramide induced
      apoptosis. Granzyme B shares a substrate sequence preference with upstream
      caspases capable of activating themselves and other caspases downstream. Z-IETD
      FMK, which inhibits caspase 8/FLICE also inhibited Sph/DMS induced apoptosis with
      no inhibition of apoptosis induced by either ceramide. Together, these data
      indicate that Sph/DMS act independently from ceramide in the apoptosis pathway
      and further suggest that Sph/DMS act earlier in the pathway than ceramide and are
      involved upstream of even the early proteases, whereas the point of action for
      ceramide is downstream of the early proteases but upstream from the late
      caspases.

PMID- 9541008
TI  - Expression of SNARE proteins in enteroendocrine cell lines and functional role of
      tetanus toxin-sensitive proteins in cholecystokinin release.
AB  - In neurons, synaptic vesicle exocytosis involves the formation of a core complex
      particle including syntaxin-1, synaptosomal-associated protein of 25 kDa (SNAP
      25) and vesicle-associated membrane protein (VAMP)-2/synaptobrevin. The
      expression of these proteins was investigated in a panel of cell lines, including
      lines of endocrine and intestinal origin, by Western blotting and/or
      immunocytochemistry. The three core complex proteins were detected in the
      enteroendocrine, cholecystokinin (CCK)-secreting, cell lines STC-1 and GLUTag,
      and in the endocrine non-intestinal cell lines CA-77 and HIT-T15. In contrast,
      SNAP-25 and syntaxin-1 were undetected in the intestinal non-endocrine cell lines
      IEC-6, HT-29 and Caco-2, whereas a slight expression of VAMP-2 was documented in
      IEC-6 and HT-29 cells. Co-immunoprecipitation experiments indicated that syntaxin
      1, SNAP-25 and VAMP-2 were present in a complex similar to that identified in
      brain. In the STC-1 cell line, treatment of streptolysin-O-permeabilized cells
      with tetanus toxin (Tetx) selectively cleaved VAMP-2 and VAMP-3/cellubrevin, and
      simultaneously abolished Ca2+-induced CCK secretion (IC50 approximately 12 nM).
      These results show that endocrine cell lines of intestinal origin express
      syntaxin-1, SNAP-25 and VAMP-2, and suggest a key role for a Tetx-sensitive
      protein (for example VAMP-2 and/or VAMP-3) in the CCK secretion by STC-1 cells.

PMID- 9541009
TI  - The Na+,K+-ATPase carrying the carboxy-terminal Ca2+/calmodulin binding domain of
      the Ca2+ pump has 2Na+,2K+ stoichiometry and lost charge movement in Na+/Na+
      exchange.
AB  - An altered ion-transport stoichiometry from 3Na+,2K+ to 2Na+,2K+ is observed in a
      chimeric Na+,K+ATPase, which carries the Ca2+/calmodulin binding domain (CBD) of
      the plasma membrane Ca2+-ATPase at its carboxy-terminus [Zhao et al., FEBS Lett.
      408 (1997) 271-2751. The ouabain-resistant mutant of this chimera (ORalpha1-CBD)
      was constructed to further investigate the effect of the CBD on ion-transport
      properties. The ORalpha1-CBD still shows the 2Na+,2K+ stoichiometry. The loss of
      electrogenicity is accompanied by the disappearance of transient charge movements
      in the Na+/Na+ exchange mode. We conclude that the binding of the third Na+ ion,
      but not of the two others, in 3Na+,2K+ transport mode apparently senses the
      electric field, and that the voltage-dependent Na+ binding is likely to be lost
      in the chimera with CBD.

PMID- 9541010
TI  - Origin of octameric creatine kinases.
AB  - Mitochondrial creatine kinase (MiCK) occurs primarily as an octameric form
      localized in the mitochondrial intermembrane compartment in vertebrate tissues
      and echinoderm spermatozoa (both deuterostome groups). The octameric quaternary
      structure is thought to play important functional and enzyme targeting roles. We
      have found that the spermatozoa of the protostome polychaete Chaetopterus
      variopedatus contain three distinct isoenzymes of creatine kinase (CK) termed
      CK1, CK2 and CK3. CK3 appears to be present only in the sperm head/midpiece
      complex where mitochondria are restricted and has a subunit relative molecular
      mass (Mr) of 43.4 kDa. Gel permeation chromatography using Superdex 200HR showed
      that CK3 has a native Mr of 344.9 kDa indicating that this enzyme exists as an
      octamer. Electron micrographs of negatively stained CK3 preparations show
      structures which are virtually identical to those that have been seen for
      octameric vertebrate MiCK. The above observations show that CK3 from C.
      variopedatus displays great similarities to MiCKs from vertebrates and
      echinoderms. Octamerization of CK is not an advanced feature. The evolution of
      octameric subunit association is ancient and occurred prior to the divergence of
      protostomes and deuterostomes.

PMID- 9541011
TI  - Molecular cloning and characterization of two novel transport proteins from rat
      kidney.
AB  - The recent cloning of renal transport systems for organic anions and cations
      (OAT1, OCT1, and OCT2) opened the possibility to search, via polymerase chain
      reaction (PCR) homology screening, for novel transport proteins. Two integral
      membrane proteins, UST1 and UST2, were cloned from rat kidney. RT-PCR revealed
      that UST1 is confined to the kidney whereas UST2 mRNA was detected in all tested
      tissues. Sequence analyses suggest that UST1 and UST2, together with four related
      transporters, comprise, within the major facilitator superfamily, a so far
      unrecognized transporter family, termed amphiphilic solute facilitator (ASF)
      family. Characteristic signatures for the ASF family were identified.

PMID- 9541012
TI  - Proteasome function is dispensable under normal but not under heat shock
      conditions in Thermoplasma acidophilum.
AB  - Hitherto the biology of proteolysis in prokaryotes, particularly in archaea, is
      only poorly understood. We have used the tri-peptide vinyl sulfone inhibitor
      carboxybenzyl-leucyl-leucyl-leucine vinyl sulfone (Z-L3VS) to study the in vivo
      function of proteasomes in Thermoplasma acidophilum. Z-L3VS is a potent inhibitor
      of the Thermoplasma proteasome and is capable of modifying 75 to 80% of the
      proteasomal beta-subunits in cell cultures. Inhibition of proteasomes has only
      marginal effects under normal growth conditions. Under heat shock conditions,
      however, the effects of proteasome inhibition are much more severe, to the extent
      of complete cell growth arrest. These data suggest that other proteolytic systems
      may exist that can compensate for the loss of proteasome function in T.
      acidophilum.

PMID- 9541013
TI  - Specific inhibition of influenza virus RNA polymerase and nucleoprotein gene
      expression by circular dumbbell RNA/DNA chimeric oligonucleotides containing
      antisense phosphodiester oligonucleotides.
AB  - We have designed a new class of oligonucleotides, 'dumbbell RNA/DNA chimeric
      oligonucleotides', consisting of a sense RNA sequence and its complementary
      antisense DNA sequence, with two hairpin loop structures. The reaction of the
      nicked (NDRDON) and circular (CDRDON) dumbbell RNA/ DNA chimeric oligonucleotides
      with RNase H gave the corresponding antisense phosphodiester oligodeoxynucleotide
      together with the sense RNA cleavage products. The liberated antisense
      phosphodiester oligodeoxynucleotide was bound to the target RNA, which gave RNA
      cleavage products by treatment with RNase H. The circular dumbbell RNA/DNA
      chimeric oligonucleotide showed more nuclease resistance than the linear
      antisense phosphodiester oligonucleotide (anti-ODN) and the nicked dumbbell
      RNA/DNA chimeric oligonucleotide. The CDRDON with four target sites (influenza
      virus A RNA polymerases (PB1, PB2, PA) and nucleoprotein (NP)) was synthesized
      and tested for inhibitory effects by a CAT-ELISA assay using the clone 76 cell
      line. The circular dumbbell DNA/ RNA chimeric oligonucleotide (CDRDON-PB2-as)
      containing an AUG initiation codon sequence as the target of PB2 showed highly
      inhibitory effects.

PMID- 9541014
TI  - Slow turnover of the D1 reaction center protein of photosystem II in leaves of
      high mountain plants.
AB  - The D1 reaction center protein of photosystem II usually exhibits a rapid
      turnover in light. The D1 protein turnover was compared in three species of
      alpine plants, Homogyne alpina, Ranunculus glacialis, Soldanella alpina, and in
      the lowland plant Taraxacum officinale by radioactive labeling in light and
      subsequent chase experiments. The D1 protein of alpine plants could also be
      recognized by its more rapid labeling, relative to other membrane proteins.
      However, compared to T. officinale the turnover of the D1 protein was
      considerably slower in the alpine plants. The potential advantage of a slow D1
      turnover for adaptation to the environmental conditions of high mountain plants
      is discussed.

PMID- 9541015
TI  - Can grafting of an octapeptide improve the structure of a de novo protein?
AB  - Structural properties and conformational stability of de novo proteins --
      albebetin and albeferon (albebetin with a grafted interferon fragment) -- were
      studied by means of CD spectroscopy, gel filtration and urea-induced unfolding.
      The results allow us to conclude that albebetin possesses the properties of the
      molten globule state. Grafting of the octapeptide to the N-terminus of this de
      novo protein affects its structure. We show here that albeferon maintains a
      secondary structure content of albebetin; it becomes more compact and much more
      stable toward urea-induced unfolding as compared to albebetin and even possesses
      some weak tertiary structure (at least around Tyr7). This means that the
      structure of the artificial protein albebetin can be improved by a simple
      procedure of octapeptide grafting to its N-terminus.

PMID- 9541016
TI  - Large quantity production with extreme convenience of human SDF-1alpha and SDF
      1beta by a Sendai virus vector.
AB  - We describe a robust expression of human stromal cell-derived factor-1alpha (SDF
      1alpha) and SDF-1beta, the members of CXC-chemokine family, with a novel vector
      system based upon Sendai virus, a non-segmented negative strand RNA virus.
      Recombinant SDF-1alpha and SDF-1beta were detected as a major protein species in
      culture supernatants, reached as high as 10 microg/ ml. This remarkable
      enrichment of the products allowed us to use even the crude supernatants as the
      source for biological and antiviral assays without further concentration nor
      purification and will thus greatly facilitate to screen their genetically
      engineered derivatives.

PMID- 9541017
TI  - Involvement of the IRF family transcription factor IRF-3 in virus-induced
      activation of the IFN-beta gene.
AB  - The virus-induced activation of interferon alpha/beta (IFN-alpha/beta) gene
      transcription is essential for host defense. The IFN-beta promoter is controlled
      primarily by the virus-inducible enhancer elements, the IRF-Es. Here we show that
      IRF-3, an IRF family transcription factor, translocates to the nucleus from the
      cytoplasm upon virus infection in NIH/3T3 cells. The nuclear IRF-3 is
      phosphorylated, interacts with the co-activators CBP/p300, and binds specifically
      to the IFN-beta IRF-E. Furthermore, overexpression of IRF-3 causes a marked
      increase in virus-induced IFN-beta mRNA expression. Thus, IRF-3 is a candidate
      transcription factor mediating the activation of the IFN-beta gene.

PMID- 9541018
TI  - Transformation system for prototrophic industrial yeasts using the AUR1 gene as a
      dominant selection marker.
AB  - We show a new transformation system for prototrophic yeast strains including
      those of Saccharomyces cerevisiae, Kluyveromyces lactis, K. marxianus, and
      Candida glabrata. This system is composed of an antibiotic, aureobasidin A (AbA),
      and its resistance gene AUR1-C as a selection marker. Southern analysis of
      genomic DNAs of the transformants indicated that the copy number of the plasmid
      increased from one to more than four, depending on the concentration of AbA used
      for selection of the transformants. The AUR1-C gene was also effective as a
      selection marker for gene disruption, and was able to disrupt both copies of the
      gene on homologous chromosomes of diploid cells by a single round of
      transformation. This system has a broad application in the transformation and
      gene disruption of prototrophic strains of a variety of yeast species.

PMID- 9541019
TI  - Altered expression of alpha-actin, smooth muscle myosin heavy chain-1 and
      calponin in cultured smooth muscle cells by oxidized low density lipoproteins.
AB  - The expression of the contractile proteins, alpha-actin, smooth muscle myosin
      heavy chain-1 (SM1) and calponin present in smooth muscle cells (SMC) in the
      presence of oxidized low density lipoproteins (oxLDL) was investigated in two
      different cell cultures: the mouse smooth muscle cell line SVSC and rat smooth
      muscle cells (RSMC). Exposure of the cells to 187 microg protein/ml oxLDL for 24
      h reduced the expression of all three contractile proteins in both cell cultures
      when compared to cells incubated in the presence of native LDL. This
      investigation of the response of SMC contractile proteins to oxLDL may provide
      further insights into the mechanisms by which oxidatively modified LDL is
      atherogenic and suggests that oxLDL may contribute to the regulation of the
      expression of the genes responsible for the synthesis of smooth muscle cell
      contractile proteins.

PMID- 9541020
TI  - Identification of a new intermediate state that binds but not activates
      transducin in the bleaching process of bovine rhodopsin.
AB  - Using time-resolved low-temperature spectroscopy, we have examined whether or not
      bovine rhodopsin has a unique transducin-binding state, meta Ib, previously
      detected from chicken rhodopsin. Unlike chicken meta Ib, bovine meta Ib was
      detected only by detailed kinetics analysis of the bleaching process, but it was
      stabilized by transducin and visualized in the observed spectral changes. From
      the effect of GTPgammaS, it was revealed that meta Ib induced no GDP-GTP exchange
      reaction in transducin. Thus meta Ib is a common intermediate of vertebrate
      rhodopsin and transducin is activated in two steps by meta Ib and meta II.

PMID- 9541022
TI  - Lipopolysaccharide-caused fragmentation of individual microtubules in vitro
      observed by video-enhanced differential interference contrast microscopy.
AB  - Microtubule disassembly is commonly believed to be a process of endwise tubulin
      dimer release. The present study demonstrates by video interference contrast
      microscopy that Escherichia coli lipopolysaccharide (LPS) caused microtubule
      disassembly in vitro by both endwise shortening and fragmentation. In contrast,
      the microtubules were only shortened from their ends in the presence of DNA, used
      as another example of a macromolecular microtubule effector. LPS-caused
      microtubule fragmentation was confirmed by transmission electron microscopy.
      Because of its ability to induce both fragmentation and endwise shortening, LPS,
      which is involved in sepsis pathogenesis, has to be regarded as a highly active
      microtubule-destabilizing agent.

PMID- 9541021
TI  - Antibacterial activity of a novel 26-kDa serine protease in the yellow body of
      Sarcophaga peregrina (flesh fly) pupae.
AB  - We have reported a novel serine protease produced by Sarcophaga peregrina
      (Nakajima et al., J. Biol. Chem. 272 (1997) 23805-23810). This 26-kDa protease
      showed antibacterial activity against several bacteria. This activity was an
      intrinsic characteristic of the enzyme protein and not directly related to its
      protease activity, because treating the 26-kDa protease with diisopropyl
      fluorophosphate had no appreciable effect on its antibacterial activity. Unlike
      bovine trypsin, the 26-kDa protease interacted with acidic phospholipids,
      suggesting that its antibacterial activity is attributable to interaction with
      bacterial membranes.

PMID- 9541023
TI  - A somatostatin receptor 1 selective ligand inhibits Ca2+ currents in rat
      insulinoma 1046-38 cells.
AB  - Rat insulinoma 1046-38 cells represent a model system to study beta-cell
      function. The mRNAs for sst1 and sst2, two of the five somatostatin receptors,
      were detected by reverse transcription polymerase chain reaction amplification in
      these cells. Displacement binding analysis suggested that sstl represents the
      major somatostatin receptor subtype. The sstl selective compound CH-275 did not
      inhibit adenylyl cyclases while compounds that activated sst2 did. In contrast,
      CH-275 caused a marked inhibition of voltage-operated Ca2+ channels while the
      sst2 specific analog octreotide elicited a less pronounced effect suggesting that
      in rat insulinoma 1046-38 cells sst1 preferably mediates the inhibition of Ca2+
      channels.

PMID- 9541024
TI  - The cell adhesion molecule C-CAM is a substrate for tissue transglutaminase.
AB  - C-CAM, a ubiquitously expressed cell adhesion molecule belonging to the
      carcinoembryonic antigen family, appears as two co-expressed isoforms, C-CAM-L
      and C-CAM-S, with different cytoplasmic domains, that can form homodimers in
      epithelial cells. In addition, C-CAM-L has been found in large molecular weight
      forms suggesting posttranslational, covalent modification. Here we have
      investigated the possibility that the cytoplasmic domain of C-CAM-L can act as a
      transglutaminase substrate. Glutathione S-transferase fusion proteins of the
      cytoplasmic domains of rat and mouse C-CAM-L as well as free cytoplasmic domains,
      released by thrombin cleavage from the fusion proteins, were converted into
      covalent dimers by tissue transglutaminase. These results demonstrate that the
      cytoplasmic domains of rat and mouse C-CAM-L are substrates for tissue
      transglutaminase, and lend support to the notion that higher molecular weight
      forms of C-CAM-L are formed by transglutaminase modification.

PMID- 9541025
TI  - Overexpression of EGFR and c-erbB2 causes enhanced cell migration in human breast
      cancer cells and NIH3T3 fibroblasts.
AB  - Overexpression of EGFR and c-erbB2 frequently occurs in human breast cancers,
      correlating with poor prognosis. Here we show that overexpression of EGFR and c
      erbB2 in cell lines increases cell migration, an important step in metastasis
      formation. The effect of EGFR on migration is dependent on the addition of EGF to
      the cells. In contrast, c-erbB2 seems to act independently of its ligand in these
      assays. Overexpression of this receptor is sufficient to induce cell migration.
      In addition, we investigated the involvement of a number of signal transduction
      pathways known to be activated by the EGFR. We found that inactivation of MAPKK
      results in a decreased migration, while inactivation of PI3K increases migration.

PMID- 9541026
TI  - Identification of an ABC transporter gene that exhibits mRNA level overexpression
      in fluoroquinolone-resistant Mycobacterium smegmatis.
AB  - We describe here the PCR amplification of a DNA fragment (mtp1) from
      Mycobacterium smegmatis using primers derived from consensus sequences of the ABC
      family of transporters. The fragment encodes amino acid sequences that exhibited
      significant homology with different ABC transporters. Amino acid sequence
      alignment of the full length gene with other transporters identified the ABC
      protein as the B-subunit of the phosphate specific transporter. Strikingly, a M.
      smegmatis colony which exhibited a high level of ciprofloxacin resistance showed
      mRNA level overexpression of mtp1. Thus this is the first report in any
      prokaryote indicating differential expression of an ABC transporter in a
      fluoroquinolone resistant colony.

PMID- 9541027
TI  - Folding and binding activity of the 3'UTRs of Paracentrotus lividus bep
      messengers.
AB  - Bep mRNAs are localized at the animal pole of P. lividus eggs. In the present
      communication the secondary structures of the 3'UTRs of the bep1, bep3 and bep4
      mRNAs are reported. The minimal lengths of these regions required to bind the 54
      kDa protein, previously shown to be involved in localization and anchoring of
      these RNAs, is estimated. Microinjection of the bep3 3'UTR into egg shows that
      this RNA fragment is also able to become localized to one of the egg poles, as
      happens for the entire bep3 RNA.

PMID- 9541029
TI  - Characterization of protein kinase C-mediated phosphorylation of the short
      cytoplasmic domain isoform of C-CAM.
AB  - C-CAM is a ubiquitously expressed cell adhesion molecule belonging to the
      carcinoembryonic antigen family. Two co-expressed isoforms, C-CAM-L and C-CAM-S,
      are known, having different cytoplasmic domains both of which can be
      phosphorylated in vivo. Here we have characterized the PKC-mediated
      phosphorylation of the short cytoplasmic domain isoform, C-CAM-S. Phorbol
      myristyl acetate induced phosphorylation of C-CAM-S in transfected CHO cells.
      Using synthetic peptides and Edman degradation we identified Ser449 as the PKC
      phosphorylated amino acid residue. Binding experiments with modified peptides
      indicated that this phosphorylation decreases the ability of the cytoplasmic
      domain of C-CAM-S to bind calmodulin.

PMID- 9541028
TI  - Overexpression, purification, crystallization and preliminary X-ray diffraction
      analysis of the pMV158-encoded plasmid transcriptional repressor protein CopG.
AB  - Plasmid pMV158 encodes a 45 amino acid transcriptional repressor, CopG, which is
      involved in copy number control. A new procedure for overproduction and
      purification of the protein has been developed. The CopG protein thus obtained
      retained its ability to specifically bind to DNA and to repress its own promoter.
      Purified CopG protein has been crystallized using the sitting-drop vapor
      diffusion method. The crystals, belonging to orthorhombic space group C222(1)
      (cell constants a = 67.2 A, b = 102.5 A, c = 40.2 A), were obtained from a
      solution containing methylpentanediol, benzamidine and sodium chloride, buffered
      to pH 6.7. Complete diffraction data up to 1.6 A resolution have been collected.
      Considerations about the Matthews parameter account for the most likely presence
      of three molecules in the asymmetric unit (2.27 A3/Da).

PMID- 9541030
TI  - Oxygen induces fatty acid (n-6)-desaturation independently of temperature in
      Acanthamoeba castellanii.
AB  - Induction of a microsomal oleate delta12 (n-6) desaturase which is mainly
      responsible for an increase in membrane lipid unsaturation at low temperature has
      been observed in the free-living amoeba Acanthamoeba castellanii. In this study
      we show that the enzyme can also be regulated by oxygen independently of
      temperature in batch cultures grown to O2-limitation. Raising the oxygen
      concentration from below the lower limit of detection (< 0.1 microM) to
      approximately air-saturation (230 microM), whilst maintaining the growth
      temperature constant (30 degrees C), increased lipid unsaturation and elevated n
      6-desaturase activity 2.3-fold. Addition of the protein synthesis inhibitor,
      anisomycin, showed that increased desaturase activity was due to new protein
      synthesis rather than activation of pre-existing enzyme. These observations are
      important for future studies of the mechanism of temperature adaptation in
      poikilotherms.

PMID- 9541031
TI  - High affinity calmodulin target sequence in the signalling molecule PI 3-kinase.
AB  - In this study we report that phosphatidylinositol 3-kinase (PI 3-kinase), a lipid
      kinase which participates in downstream signalling events of heterotrimeric G
      protein-coupled receptors and receptor tyrosine kinases, contains a high affinity
      binding site for calmodulin (CaM). The putative CaM-binding peptide derived from
      the p110gamma isoform interacts with CaM in a calcium-dependent way. Using gel
      shift analysis and fluorescence spectrophotometry we discovered that the peptide
      forms a high affinity complex with CaM. Titration experiments using dansylated
      CaM gave an affinity constant of 5 nM. Furthermore, a sequence comparison among
      different PI 3-kinase isoforms revealed that the sequence which can bind CaM is
      highly conserved within different PI 3-kinase isoforms. These results indicate a
      novel mechanism for regulating PI 3-kinase and provide a new direct link between
      Ca2+ and phospholipid signalling pathways.

PMID- 9541033
TI  - How dangerous is the unintentional use of the word accident in our literature?

PMID- 9541032
TI  - Dexamethasone stimulates the expression of GLUT1 and GLUT4 proteins via different
      signalling pathways in L6 skeletal muscle cells.
AB  - It was recently demonstrated that dexamethasone treatment of L6 skeletal muscle
      cells resulted in an elevation of GLUT1 protein. However, the level of GLUT4
      protein under these conditions was not examined. In addition, the signalling
      mechanism(s) leading to dexamethasone-induced expression of GLUT1 protein was not
      investigated. In the present study we investigated the effect of dexamethasone on
      the expression of GLUT1 and GLUT4 proteins in differentiated L6 muscle cells and
      the signalling mechanism(s) via which dexamethasone may act. Dexamethasone (300
      nM) treatment for 24 h elevated GLUT1 and GLUT4 proteins by 68% and 94%,
      respectively, above control levels. These increases were due to de novo synthesis
      as shown by metabolic labelling with [35S]methionine. Incubation of cells with
      100 nM wortmannin or 30 ng/ml rapamycin prevented the dexamethasone-stimulated
      elevation of GLUT1 protein. In contrast, neither of these inhibitors affected the
      elevation of GLUT4 protein by dexamethasone. Furthermore, dexamethasone down
      regulated insulin receptor substrate-1 protein content by 42% and insulin-induced
      tyrosine phosphorylation of insulin receptor substrate-1 by 28%. The p70
      ribosomal S6 kinase was not activated by dexamethasone and instead, dexamethasone
      attenuated the stimulation of this enzyme activity by insulin. These results
      suggest that dexamethasone induces the expression of GLUT1 and GLUT4 protein by
      independent signalling mechanisms with a concomitant depression of intracellular
      signalling by insulin.

PMID- 9541034
TI  - Variation in human plasma cholinesterase activity during low-dose cocaine
      administration.
AB  - BACKGROUND: Cocaine is metabolized by a number of enzymes, the activity of one of
      which, plasma cholinesterase has been associated with dinical manifestations of
      toxicity. Patients with life-threatening complications of cocaine intoxication
      have lower plasma cholinesterase activity than less toxic controls. In addition,
      relatively healthy cocaine users have lower plasma cholinesterase activity than
      noncocaine using controls. Thus, low plasma cholinesterase activity could be a
      contributing factor to cocaine toxicity, a consequence of cocaine use, or a
      confounding variable. The following study was designed to further assess the
      relationship between cocaine use and plasma cholinesterase activity. METHODS: We
      studied fluctuations in plasma cholinesterase activity in nine subjects enrolled
      in an inpatient study of the behavioral pharmacology of smoked cocaine. Subjects
      used at least 2 g of cocaine weekly for at least 1 year prior to enrollment. The
      subjects were admitted to the research unit where they remained drug-free for 2
      days. They then received smoked cocaine for 4 days (up to 405 mg over 5 hours
      daily) and were then drug-free again for 2 days. Plasma cholinesterase activity
      was measured at 9 AM and 4 PM each day. RESULTS: Baseline plasma cholinesterase
      ranged from 265 to 930 U/L (normal > 450 U/L). The mean plasma cholinesterase
      increased 112+/-100 U/L from day 1 to day 8 (p = 0.025). There was no daily
      change in plasma cholinesterase levels from 9 AM to 4 PM (15+/-165 U/L, p > 0.6),
      and there was no difference in the daily change between high- and low-dose
      cocaine days (-3+/-137 U/L vs 28+/-165 U/L, p = 0.52). CONCLUSION: These
      preliminary data suggest that plasma cholinesterase levels do not change over a 7
      hour period as a result of cocaine administration, but may increase during a
      period of inpatient study. Such an increase could potentially influence the
      pharmacokinetics or effects of cocaine studied in an inpatient setting and may
      give insight into the etiology of the observed low-plasma cholinesterase activity
      in cocaine users.

PMID- 9541035
TI  - Opioid toxicity recurrence after an initial response to naloxone.
AB  - OBJECTIVE: To determine the frequency and potential predictors of opioid toxicity
      recurrence after a response to naloxone in adult Emergency Department patients.
      METHODS: A retrospective case-control study of naloxone-treated patients with
      opioid toxicity over an 8-year period. Both the patient response to naloxone and
      recurrence of opioid toxicity was determined by an expert Delphi Panel. The
      frequency of opioid toxicity recurrence was compared by the duration of opioid
      effect, the route of opioid exposure, and the presence of other CNS depressant
      drugs. RESULTS: Ninety of 221 (41%) cases with a discharge diagnosis of opioid
      toxicity were treated with naloxone; six patients were excluded because of a lack
      of toxicity. There was a response to naloxone in 50% of the 84 cases, and
      recurrence of toxicity in 31% (95% CI 17-45%) of naloxone responders. The most
      common opioids were codeine, heroin, propoxyphene, and oxycodone/hydrocodone.
      Recurrence of toxicity was more common with long-acting opioids (p = 0.04), and
      was not associated with the route of opioid exposure (p = 0.42), or presence of
      ethanol and other CNS depressants (p > or = 0.87). CONCLUSION: Opioid toxicity
      recurrence after a response to naloxone occurred in approximately 1/3 of adult
      Emergency Department opioid overdose cases. Recurrence was more common with long
      acting opioids and was not associated with the route of opioid exposure. Other
      clinically useful predictors of toxicity recurrence were not identified.

PMID- 9541036
TI  - Use of ondansetron and other antiemetics in the management of toxic acetaminophen
      ingestions.
AB  - BACKGROUND: Patients presenting with acetaminophen toxicity and vomiting are
      often treated with antiemetics so that orally administered N-acetylcysteine can
      be retained. The policy at the West Virginia Poison Center is to reserve
      ondansetron, an antiemetic with a higher cost than other antiemetics, as a second
      line agent for patients presenting within 8 hours of an acetaminophen ingestion.
      METHODS: A retrospective study of cases between January 1993 and December 1995,
      in which the primary or secondary drug ingested was an adult-strength,
      acetaminophen-only formulation and the ingestion resulted in vomiting. Seventy
      eight patients with laboratory-verified acetaminophen toxicity and vomiting were
      evaluated for the type of antiemetics used and the antiemetic's effectiveness.
      RESULTS: Of the 78 acetaminophen toxic patients with vomiting, 17/51 patients
      (33.3%) who received a nonondansetron antiemetic failed therapy and required IV
      ondansetron. Of the 24 patients who received ondansetron, 4 patients (16.7%)
      failed therapy. All four patients who failed ondansetron therapy had previously
      failed other antiemetic therapy. DISCUSSION: Although ondansetron had a lower
      failure rate than nonondansetron antiemetics, almost two-thirds of acetaminophen
      toxic patients with vomiting did not require ondansetron to control their
      vomiting. Health care costs would have been higher had these patients received
      ondansetron as their initial therapy. Antiemetics were found to be highly
      effective as only 3/78 patients (4%) required IV N-acetylcysteine secondary to
      antiemetic failure. CONCLUSIONS: Ondansetron should be utilized as a second-line
      agent in the management of acetaminophen toxic patients with vomiting. Because of
      its lower failure rate, ondansetron should be administered as a first-line agent
      in patients with a delay in N-acetylcysteine administration approaching 8 or more
      hours.

PMID- 9541037
TI  - Survival after massive arsenic poisoning self-treated by high fluid intake.
AB  - CASE REPORT: A 23-year-old male pharmacist ingested 1040 mg arsenic trioxide (788
      mg trivalent arsenic, 13 mg/kg). After 7 asymptomatic hours, frequent vomiting
      and diarrhea occurred. Fearing death from shock, he drank 5 L of water over 5
      hours. When he was brought to our hospital with chief complaint of constricted
      vision about 20 hours after ingestion, the major abdominal symptoms had already
      subsided. Despite a lethal plasma arsenic on admission, all toxic symptoms
      including hepatic dysfunction, erythematous dermal eruption, and peripheral
      neuropathy improved during his hospital stay with no treatment except for
      dimercaptopropanol.

PMID- 9541038
TI  - Fatal serotonin syndrome caused by moclobemide-clomipramine overdose.

PMID- 9541040
TI  - Atropinism following rectal administration of a therapeutic atropine dose.

PMID- 9541039
TI  - Clinical experience in acute overdosage of diphenidol.
AB  - BACKGROUND: Diphenidol (Cephadol, Vontrol), an antiemetic agent used in the
      treatment of vomiting and vertigo, has been reported to cause various adverse
      effects including drowsiness, hypotension, confusion, hallucination,
      restlessness, and other antimuscarinic effects. Serious toxic effects might be
      anticipated after intentional or accidental ingestion. MATERIALS AND METHODS:
      Retrospective analysis of all case records of the PCC-Taiwan defining diphenidol
      overdose during 1985-1996. RESULTS: The data of 21 patients with diphenidol
      overdose were analyzed; 17 were < 3 years old and unintentionally poisoned, in
      contrast to the suicide attempts by four adults. The average amount of ingestion
      was 222.5 mg with a range of 25-800 mg. Most patients manifested only transient
      CNS, cardiovascular, or oculo-facial effects, but four children suffered from
      severe toxicity after an ingestion of 11.7-80 mg/kg diphenidol. Commonly reported
      toxicity in diphenidol overdose included facial flush (10), tachycardia,
      restlessness (6), seizures (4), dyspnea, drowsiness, mydriasis, coma, and fever
      (3). With supportive therapy, a good recovery was the rule except for one
      fatality of a 2 1/2-year-old boy who ingested 15 mg/kg diphenidol and presented
      with recurrent seizures, hypotension, respiratory failure, and coma. CONCLUSIONS:
      Although not previously reported, accidental diphenidol overdose may result in
      serious anticholinergic toxicity in children. Treatment is supportive and the
      therapeutic role of physostigmine in diphenidol poisoning is still unclear.

PMID- 9541041
TI  - Central anticholinergic syndrome due to Jimson weed physostigmine: therapy
      revisited?

PMID- 9541042
TI  - Psilocybin mushroom (Psilocybe semilanceata) intoxication with myocardial
      infarction.
AB  - CASE REPORT: Intentional intoxication with natural hallucinogenic substances such
      as hallucinogenic mushrooms continues to be a major problem in the US and Europe,
      particularly in the harbor complex of northwest Poland (Pomerania). A case is
      described of Psilocybe intoxication in an 18-year-old man resulting in Wolff
      Parkinson-White syndrome, arrhythmia, and myocardial infarction. The indole
      concentrations of hallucinogenic mushrooms may predict the risk for adverse
      central nervous system and cardiac toxicity.

PMID- 9541043
TI  - The dangers of pet tarantulas: experience of the Marseilles Poison Centre.

PMID- 9541044
TI  - The dangers of pet tarantulas: experience of the Marseilles Poison Centre.

PMID- 9541045
TI  - Permethrin emulsion ingestion: clinical manifestations and clearance of isomers.
AB  - BACKGROUND: Oral intoxication with permethrin, an insecticide which prolongs
      axonal sodium channel depolarization, has not been documented in humans. We
      treated a 59-year-old man who drank approximately 600 mL of 20% permethrin
      emulsion in a suicide attempt. METHODS: Sequential blood samples were obtained to
      determine permethrin isomer levels using high-performance liquid chromatography.
      RESULTS: Vomiting and diarrhea occurred after ingestion. On admission, loss of
      consciousness and metabolic acidosis were observed. On regaining consciousness,
      the patient complained of a burning sensation in the oral cavity. He received
      fluid therapy after gastric lavage and recovered without severe complications.
      Apart from initially impaired consciousness, no clinical neurotoxicity such as
      tremor, hyperexcitation, ataxia, convulsions, or paralysis occurred, though these
      have been reported in permethrin-intoxicated animals. Serum permethrin
      concentrations peaked 3-4 hours after ingestion at 868 ng/mL. Clearance of trans
      permethrin was more rapid than that of cis permethrin. CONCLUSION: The unequal
      clearance of permethrin isomers paralleled findings in animal experiments.
      Vomiting and diarrhea probably limited absorption in the present case, resulting
      in a peak serum concentration and a degree of neurotoxicity far less than those
      seen in animals.

PMID- 9541046
TI  - Quantitation of postmortem profenofos levels.
AB  - CASE REPORT: An 88-year-old woman was found dead, and suicidal ingestion of
      profenofos, an organophosphate pesticide, was suspected. METHOD: Gas
      chromatography-nitrogen phosphorus detection was employed for quantitation of
      profenofos after its identification by gas chromatography/mass spectrometry.
      RESULTS: The levels of profenofos in whole blood, urine, and gastric contents
      were 1200 ng, 350 ng, and 3.35 mg/mL, respectively.

PMID- 9541047
TI  - Acute chemical pancreatitis associated with nonfatal strychnine poisoning.
AB  - CASE REPORT: An 18-year-old female who accidentally ingested strychnine developed
      chemical pancreatitis in addition to the classical clinical picture of strychnine
      poisoning. Many drugs or chemicals have been reported to be associated with
      pancreatitis; however, this paper provides us with the first evidence that acute
      pancreatitis may follow strychnine poisoning. The patient survived despite the
      development of seizures, lactic acidosis, rhabdomyolysis, and pulmonary
      infiltrates. Toxicology testing confirmed the presence of strychnine in blood
      (2.17 mg/L), gastric aspirate, and urine. Attention is drawn to the fact that
      survival can follow the ingestion of large doses of strychnine providing there is
      no delay in diagnosis and treatment. The pathophysiologic mechanism of chemical
      pancreatitis is discussed.

PMID- 9541048
TI  - A poison information service via an automated facsimile (fax) system: an adjunct
      to the operator-based service.
AB  - BACKGROUND: Poison centers are faced with the escalating costs of specialist
      staffing and increased investments in hardware and databases despite deficit
      funding. We developed an automated fax information system to access poison
      information from any fax machine without special training or equipment. METHODS:
      We provided a 3-month trial service of the fax system in conjunction with the
      regular operator-based service and analyzed the fax access log, followed by a
      questionnaire to the 2204 affiliate members regarding the use of the fax.
      RESULTS: A total 657 accesses to the fax system were made, of which 105 (16%)
      were unsuccessful; 342 (52%) were made to retrieve the user's manual, 85 (13%) to
      retrieve the index pages, and 230 (35%) to retrieve documentation on specific
      substances. The most frequently accessed items concerned disc battery ingestion
      (13.5%), salicylates (10.3%), mamushi viper (7.1%), acetaminophen (5.8%), and
      sodium hypochlorite (3.8%). The questionnaires were returned by 666 (30.2%)
      members; 93 (14%) had actually used the fax system with the average frequency of
      1.8 times/user, 63% (59/93) of the respondents considered the service
      satisfactory, and 33% (31/93) said it was somewhat unsatisfactory. CONCLUSIONS:
      The automated fax information system was accepted and handled by users with only
      minor difficulty. A facsimile information service may have a valuable role in
      providing poisoning information and has potential benefits in cases of
      environmental disasters.

PMID- 9541049
TI  - Technology in poison centers: cutting edge or cutting services?

PMID- 9541050
TI  - Stachybotrys, a mycotoxin-producing fungus of increasing toxicologic importance.
AB  - BACKGROUND: Stachybotrys as a fungus has been implicated as a source of
      mycotoxins. While the toxicity of several well-known mycotoxins (aflatoxins) is
      well documented, recent studies on Stachybotrys have raised the question that
      mycotoxins produced by this fungus may be responsible for the health effects of
      occupants in water-damaged buildings. METHODS: Published articles regarding
      Stachybotrys-related mycotoxins were reviewed with particular focus on human
      toxicity. RESULTS: A critical review of papers, reports, and studies on
      Stachybotrys mycotoxins revealed only descriptive reports of suspected animal and
      human poisoning secondary to consumption of mold-contaminated food products. No
      studies of good toxicologic and epidemiologic designs answer whether airborne
      mycotoxins produced by Stachybotrys could produce specific human toxicity.
      CONCLUSIONS: Current data on the toxicology of mycotoxins produced by
      Stachybotrys demonstrate that this group of mycotoxins is capable of producing
      immunosuppression and inflammatory insults to gastrointestinal and pulmonary
      systems. Case control study and case reports have suggested a possible
      association with environmental exposure to Stachybotrys mycotoxins, although a
      firm causal relationship has not been firmly established. Additional studies are
      needed to document that humans with sufficient exposure to these mycotoxins
      develop compatible clinical and pathologic pictures as demonstrated in animal
      models.

PMID- 9541051
TI  - Chlorine inhalation: the big picture.
AB  - BACKGROUND: Causes of acute chlorine exposures from community pool accidents have
      many reported etiologies. This case series involves 13 children exposed to high
      levels of chlorine at two community pools after an unusual mishap in the
      chlorination maintenance procedure. CASE REPORT: During maintenance, the water
      feeding lines to pools are normally turned off, the chemicals replaced, the water
      turned back on, and the chemicals then reinjected into the line. In two separate
      disasters in the summer of 1996, the feeding lines were not reprimed with water
      before the reactants, sodium hypochlorite and muriatic acid, were injected. This
      caused an unusually high volume of concentrated chlorinated water to be released
      when refed to the pool. RESULTS: All patients were treated with beta agonists and
      humidified oxygen, and five were admitted. None received bicarbonate inhalation.
      An extensive literature review of chlorine inhalation injuries indicates
      considerable variance in opinions of the pathophysiology, clinical presentation
      and treatment modalities, especially steroids and bicarbonate inhalation.
      CONCLUSION: In community pools, failure to reprime feeding lines with water after
      replacing and injecting chlorinating reactants may result in severe and large
      scale chlorine exposures. Beta agonist administration and humidified oxygen
      remains the mainstay of treatment; steroid therapy and bicarbonate inhalation are
      still inadequately supported.

PMID- 9541052
TI  - Toluene diisocyanate exposure in a glove manufacturing plant.
AB  - CASE REPORT: An accidental exposure due to reuse of containers of toluene
      diisocyanate to transport nontoxic substances and subsequent occupational toxic
      exposure caused illness among forty workers in a glove manufacturing plant.
      Examination and investigation of the patients and factory site inspection were
      carried out. Toluene diisocyanate-contaminated latex was examined by the infrared
      spectroscopy. Thirty-two of forty patients had muscle pain and seven had elevated
      creatine phosphokinase activity. These features have not been reported previously
      as components of toluene diisocyanate toxicity and their underlying causation
      remains speculative.

PMID- 9541053
TI  - Zinc gluconate: acute ingestion.
AB  - CASE REPORT: Despite the popularity of zinc gluconate for use in attenuation of
      common cold symptoms, there is little information on the effects of acute
      overdose. A 17-year-old male ingested approximately 85 tablets or 4 g zinc
      gluconate (570 mg elemental zinc). He experienced severe nausea and vomiting
      within 30 minutes of the ingestion but had no further sequelae such as diarrhea,
      gastric erosions, esophageal burns, shock, neurologic dysfunction, symptoms of
      anemia, or hepatic inflammation. Serum zinc level was 4.97 mg/dL at approximately
      5 hours postingestion.

PMID- 9541054
TI  - The carbon monoxide poisoning of two Byzantine emperors.
AB  - CASE REPORT: In this paper, two possible cases of acute carbon monoxide poisoning
      previously not identified in the medical and historical literature are discussed.
      The first concerns the famous Byzantine Emperor Julian the Apostate, who may have
      suffered mild carbon monoxide poisoning from which he quickly and completely
      recovered. The second case involves his successor, Jovian, who may have succumbed
      to severe carbon monoxide poisoning. Both cases were in all likelihood due to the
      burning of coal in braziers, a usual method of indoor heating during that epoch.

PMID- 9541055
TI  - Carbamazepine interference with an immune assay for tricyclic antidepressants in
      plasma.
AB  - BACKGROUND: Drug toxicological screening is commonly used as a diagnostic tool in
      patients with suspected toxic ingestion. False positive results due to cross
      reactive compounds in drug assays may lead to misdiagnosis and mismanagement,
      especially when child abuse is suspected. CASE REPORT: Two of our patients with
      history of ingestion of carbamazepine were tested positive on screening with the
      tricyclic antidepressant immunoassay. The immunoassay's known cross-reactivity
      for carbamazepine is reportedly as low as 0.3%. Plasma samples of our patients
      were initially considered positive for tricyclic antidepressants because the
      cross-reaction of carbamazepine gave tricyclic antidepressant concentrations as
      imipramine equivalent sufficiently above the assay cut-off point (20 ng/mL).
      Later, confirmatory urine testing of both patients using high-performance liquid
      chromatography was negative for tricyclic antidepressants. CONCLUSION: This
      interference has significant clinical implications, and can be avoided on urine
      testing using a specific chromatographic assay such as high-performance liquid
      chromatography.

PMID- 9541056
TI  - Immunoassay drug screen results: easy to get, hard to interpret.

PMID- 9541057
TI  - An in vitro evaluation of fluoxetine adsorption by activated charcoal and
      desorption upon addition of polyethylene glycol-electrolyte lavage solution.
AB  - BACKGROUND: In drug overdoses, treatment with activated charcoal is frequently
      used because of its adsorptive properties. Recently, whole-bowel irrigation with
      polyethylene glycol-electrolyte lavage solution has been used as a
      gastrointestinal decontamination procedure for ingestions of toxins not well
      adsorbed to activated charcoal and for toxins with a delayed absorption phase,
      although well adsorbed to activated charcoal. While a combined approach using
      activated charcoal and whole-bowel irrigation could theoretically enhance the
      efficacy of both modalities, this improvement remains speculative, since data
      demonstrating its clinical advantage in overdose treatment are lacking.
      Fluoxetine, a selective serotonin uptake inhibitor, is one of the most frequently
      prescribed antidepressants. Fluoxetine is well adsorbed onto activated charcoal.
      This in vitro investigation was undertaken to study: a) the effect of
      polyethylene glycol, as well as polyethylene glycol-electrolyte lavage solution,
      on the adsorption of fluoxetine to laboratory grade-activated charcoal and a
      commercial activated charcoal formulation (Carbomix powder) in simulated gastric
      (pH= 1.2) and intestinal (pH=7.2) fluid environment; b) whether the order of
      polyethylene glycol-electrolyte lavage solution addition would have any effect on
      the adsorption of fluoxetine to activated charcoal. METHODS: Adsorption of
      fluoxetine to charcoal in the presence of polyethylene glycol was examined: a) by
      the simultaneous addition of polyethylene glycol and charcoal to fluoxetine
      solution and b) by the addition of charcoal to fluoxetine solution and subsequent
      addition of polyethylene glycol. In both cases, the slurries were incubated at 37
      degrees C for 1 hour and filtered. Free fluoxetine concentration was determined
      in the diluted filtrate by a reversed-phase high-performance liquid
      chromatography method. RESULTS: The amount of fluoxetine adsorbed to activated
      charcoal (or Carbomix) was dramatically decreased at gastric and intestinal pH by
      the presence of polyethylene glycol or polyethylene glycol-electrolyte lavage
      solution added either concurrently or sequentially to activated charcoal.
      CONCLUSIONS: In cases of fluoxetine overdose, administration of activated
      charcoal is recommended, while a combined approach using activated charcoal and
      whole-bowel irrigation with polyethylene glycol-electrolyte lavage solution is
      not recommended since it causes a significant desorption of the drug from
      activated charcoal.

PMID- 9541058
TI  - The measurement of nisoldipine serum concentration in a case of severe
      nisoldipine overdose.

PMID- 9541059
TI  - Fluoxetine: is the syndrome of inappropriate secretion of antidiuretic hormone in
      elderly patients associated with elevated serum levels?

PMID- 9541060
TI  - Compilations of therapeutic, toxic, and fatal concentrations of drugs.

PMID- 9541061
TI  - Good reasons to publish in Clinical Toxicology.

PMID- 9541062
TI  - Poison center data and the Pollyanna phenomenon disputed.

PMID- 9541063
TI  - Zolpidem binds to omega, not mu, receptors.

PMID- 9541064
TI  - Food and Drug Administration update. The MedWatch program.

PMID- 9541065
TI  - Wealth, equity and health care: a critique of a "population health" perspective
      on the determinants of health. Critical Social Science Group.
AB  - In this paper we examine the recent ascendancy of a "population health"
      perspective on the "determinants of health" in health policy circles as
      conceptualized by health economists and social epidemiologists such as Evans and
      Stoddart [Evans and Stoddart (1990) Producing health, consuming health care.
      Social Science & Medicine 31(12), 1347 1363]. Their view, that the financing of
      health care systems may actually be deleterious for the health status of
      populations by drawing attention away from the (economic) determinants of health,
      has arguably become the "core" of the discourse of "population health". While
      applauding the efforts of these and other members of the Canadian Institute for
      Advanced Research for "pushing the envelope", we nevertheless have misgivings
      about their conceptualization of both the "problem" and its "solutions", as well
      as about the implications of their perspective for policy. From our critique, we
      build an alternative point of view based on a political economy perspective. We
      point out that Evans and Stoddart's evidence is open to alternative
      interpretations--and, in fact, that their conclusions regarding the importance of
      wealth creation do not directly reflect the evidence presented, and are
      indicative of an oversimplified link between wealth and health. Their view also
      lacks an explicit substantive theory of society and of social change, and
      provides convenient cover for those who wish to dismantle the welfare state in
      the name of deficit reduction. Our alternative to the "provider dominance" theory
      of Evans and Stoddart and colleagues stresses that the factors or forces
      producing health status, which Evans and Stoddart describe, are contained within
      a larger whole (advanced industrial capitalism) which gives the parts their
      character and shapes their interrelationships. We contend that this alternative
      view better explains both how we arrived at a situation in which health care
      systems are as costly or extensive as they are, and suggests different policy
      avenues to those enunciated by Evans, Stoddart and their confreres.

PMID- 9541066
TI  - Perceptions and priorities in disease eradication: dracunculiasis eradication in
      Africa.
AB  - Dracunculiasis, guinea worm disease, is an incapacitating disease affecting
      people in poor, remote areas of Africa, in Yemen, and a few remaining areas of
      the Indian subcontinent where there is poor access to protected water sources.
      The neglect of this preventable disease and its belated recognition are analyzed
      within the context of changing priorities for health since the 1870s, especially
      the shift from the paradigm of Imperial Medicine to Primary Health Care. A global
      eradication effort took off during the 1980s, and, although the original target
      date of December 1995 has passed, the program has achieved a remarkable recent
      diminution in the number of recorded cases, over 99% of which are now found in
      Africa. Eradication policies in Africa are briefly explored in relation to
      current concerns such as the incorporation of dracunculiasis eradication measures
      in cash-starved primary health care programs. The wider implications of an
      eradication campaign which is on the verge of success are also considered.

PMID- 9541067
TI  - An ancient scourge: the end of dracunculiasis in Egypt.
AB  - This paper addresses the question of when guinea worm disease was last found in
      Egypt, and how written sources from the nineteenth and twentieth centuries which
      mention the disease should be evaluated. This enquiry is relevant to the global
      eradication campaign now in progress, and the need for countries in which
      dracunculiasis was once present to prepare a certification of eradication. Sudan,
      the country which has the largest number of cases today, is Egypt's southern
      neighbour. Because of the nature of the disease (in endemic areas it is most
      common among poor, rural people), it may not have come to the attention of urban
      based health personnel. In the period before the details of the transmission
      cycle were known, the attitudes and mindsets of physicians and travellers also
      have to be taken into account in interpreting written reports of the disease. An
      examination of documentary sources from the nineteenth and twentieth centuries in
      European languages does not show any clear evidence for dracunculiasis
      transmission in Egypt during that period. Cases noted in Egypt, especially by the
      much quoted Dr Clot Bey in the 1820s, most likely originated beyond the borders
      of the country, in Sudan and, to a lesser extent, from endemic areas in the
      Middle East. However, many later commentators merely repeated what Clot Bey had
      written. A further difficulty is that some published reports which apparently
      concern dracunculiasis in Egypt, actually refer to cases in animals rather than
      humans.

PMID- 9541068
TI  - Supplemental health insurance ownership in Israel: an empirical analysis and some
      implications.
AB  - Many Western nations are implementing (or considering) changes in their health
      care systems. An integral component of these changes (or debates) refers to the
      functioning and regulation of the supplementary health insurance market. However,
      only limited empirical evidence exists on the functioning of the market, which is
      prone to the problems of moral hazard, adverse selection and risk selection. This
      paper presents an empirical analysis of ownership patterns of four supplementary
      insurance policies (acute care, nursing care, dental care and emergency intensive
      care) in the Israeli population aged 45- 75 in 1993. It further discusses some
      social policy and regulation issues related to the supplemental health insurance
      market in the post-1995 era of the Israeli National Health Insurance.

PMID- 9541069
TI  - Community empowerment paradigm drift and the primary prevention of HIV/AIDS.
AB  - Long discussed in the public health arena, the concept of empowerment has only
      recently entered the discourse on the primary prevention of HIV/AIDS in the
      United States. Despite its broad appeal, empowerment has not been systematically
      incorporated into theory-based interventions, which may reflect a lack of
      consensus on the meaning of empowerment, how to measure it, and the intervention
      strategies it implies. The purpose of this paper is to consider the relevance of
      empowerment to community interventions for persons at risk for HIV, particularly
      women. The origins of empowerment are reviewed; community empowerment as an
      intervention framework is described and its core assumptions defined. There is
      some evidence of the growing influence of empowerment and related concepts in
      recent HIV-related policy, research, and programs funded through the Centers for
      Disease Control and Prevention. However, adoption of an empowerment framework for
      HIV prevention will require further theory and measurement development, as well
      as changes in how public health researchers and practitioners work with the
      communities they serve.

PMID- 9541070
TI  - Community representatives: representing the "community"?
AB  - This paper takes as its starting point the apparent disjunction between the
      assumptions of the self-evidence of the meaning of community in major
      international declarations and strategies which promote community participation
      and the observation that meanings of "community" are a subject of extensive
      debate in literatures of social analysis and to some extent health. Given that
      the word's meaning is not agreed, those working to promote "community
      participation" in health are forced to adjudicate on competing meanings in order
      to operationalise the notion. This raises questions about how this is done and
      what are the implications of particular choices for what may be achieved by the
      participating "community". This paper presents the findings of an empirical study
      which examined the manner in which ideas of "community" are operationalised by
      people engaged in encouraging community participation in health promotion in the
      context of the selection of members for health for all steering groups in healthy
      cities projects in the United Kingdom. It argues that the demands of the role of
      the "community representative" are such that particular interpretations of
      "community" achieve ascendance. The paper explores the consequences of the
      interpretation of "community" as part of the "voluntary sector" and argues that
      this may compromise one of the stated desired outcomes of community participation
      i.e. extending democracy in health decision-making.

PMID- 9541071
TI  - The importance of place for older people moving into care homes.
AB  - In an increasingly mobile society, the importance of place can be forgotten in
      the process of making decisions about where older people should receive care.
      There is some evidence, however, that issues of location and place are important
      to older people, both in the way that their sense of self is developed and
      maintained through identification with places and through their ability to
      participate in activities. This paper describes a research study which followed a
      group of older people through the process of moving into care homes, and
      discusses some of the data produced, which indicated how a sense of place shaped
      the process of moving.

PMID- 9541072
TI  - "Loss of self" in the narratives of people with traumatic brain injuries: a
      qualitative analysis.
AB  - To discover how people with traumatic brain injuries (TBI) experience themselves,
      narrative data from ten individuals with TBI were analyzed. The findings suggest
      that people with TBI experience loss of self in various forms although they may
      successfully use strategies to avoid or minimize the sense of loss. First, people
      with TBI find it difficult to develop clear self-knowledge about how they have
      become as they are and what they can and cannot do. Second, loss of self is
      conspicuous when they compare their present status with their past in many
      aspects of their lives. Third, their senses of self are threatened by labels that
      they feel the society imposes upon them. This categorization of loss of self can
      serve for rehabilitation counseling of this population. It may assist counselors
      to enhance their understanding of emotional distress after TBI and to make use of
      their clients' narratives for the intervention.

PMID- 9541073
TI  - An ethnographic study of night blindness "ratauni" among women in the Terai of
      Nepal.
AB  - Night blindness is the most common ocular condition representing moderate-to
      severe vitamin A deficiency in children. Very little, however, is known about
      maternal night blindness, which has recently been reported to occur frequently
      during pregnancy in parts of south-east Asia. In Nepal, the prevalence of night
      blindness is reported to be 16%. We carried out an ethnographic study of night
      blindness during pregnancy in the south-eastern, rural plains of Nepal as
      preliminary research for a case-control study of the determinants of this
      condition. The purpose of the research was to identify local terms and concepts
      of night blindness and to examine women's perceptions of its causes, symptoms,
      severity, and consequences during pregnancy. Data collection involved in-depth
      interviews, case studies, unstructured observations and structured anthropologic
      methods, such as free listing and quick sort ranking. Women considered night
      blindness to be an important illness of pregnancy, ranking it second (to vaginal
      bleeding) in perceived severity from a list of 15 "women's illnesses". Local
      terms for night blindness were identified in three different languages from the
      region. Informants described a complex ethnomedical model of night blindness that
      included causes, symptomatology, and treatment alternatives. However, there was
      no perceived link between food intake and the occurrence of night blindness. The
      major causes of night blindness were attributed to pregnancy, weakness, or
      "hotness". Some women sought treatment for the condition but most women chose not
      to treat it since they believed that it was a transient condition of pregnancy.
      Interviews with women who had previously experienced night blindness and home
      based observations of women exhibiting concurrent night blindness showed that it
      adversely affected their activity patterns, especially those related to child
      care and food preparation. Night blindness increased reliance on family members
      to perform various domestic chores and was also associated with personal injury
      and accidents. The findings of this study have relevance for women's reproductive
      health and nutrition throughout the Indian sub-continent. A simple history of
      night blindness may be a practical tool to identify women with nutritional and
      health risks. Maternal night blindness should be more routinely investigated in
      vitamin A deficient areas of the world, both to define the magnitude of the
      problem, and to develop programs/interventions that specifically target this
      population.

PMID- 9541074
TI  - Infertility in the Gambia: frequency and health care seeking.
AB  - In order to understand the problems of undesired infertility in the Gambia, where
      the desire for children and fertility is very high, a population based estimate
      of the frequency of sub-/infertility was undertaken. A survey was used in a
      representative random sample of the population. The study included an assessment
      of health care available for infertile couples in the different types and levels
      of the formal and traditional health system. Primary sterility was found to be
      fairly uncommon (3%), and secondary infertility to be more frequent (6%). Half of
      the infertile couples failed to seek formal health care, and they had to reach a
      certain level of care in order to be properly managed. As investigations are very
      basic and treatment possibilities scarce, many forms of alternative care are
      often sought. In addressing reproductive health in developing countries, a
      systematic primary health care approach to infertility in rural areas with
      limited resources should be developed.

PMID- 9541075
TI  - Gender differences in consulting a general practitioner for common symptoms of
      minor illness.
AB  - The aim of this paper is to examine whether, in response to the same symptoms of
      minor illness, women reported a greater propensity to consult a general
      practitioner than men. Respondents taking part in the West of Scotland Twenty-07
      Study (853 aged 39 and 858 aged 58) were presented with a check-list of 33
      symptoms during the course of a home interview conducted by nurses. They were
      asked whether they had experienced any of these symptoms in the last month, and
      if they had, whether they consulted a general practitioner about it. A summary
      indicator for reporting, or consulting for, at least one symptom was constructed,
      and statistical associations between gender, reporting and consulting for
      symptoms were examined using chi-square tests with Yates' correction. Women were
      more likely to have consulted a general practitioner for at least one of the 33
      symptoms of minor illness reported in the previous month (34% of women, 27% of
      men aged 39, chi2 = 3.97, p < 0.05; 49% of women, 43% of men aged 58, chi2 =
      3.21, (NS)). Women were significantly more likely to have consulted for five
      individual symptoms in the younger cohort, and for three symptoms in the older
      cohort, whilst men were significantly more likely to have consulted for only one
      symptom, in the younger cohort. However, when only those who had reported a
      symptom in the last month were included in analysis there were no gender
      differences in consulting for any of the 33 symptoms in the older cohort, and for
      just 3 symptoms in the younger cohort. These data do not support the most widely
      suggested explanation for gender differences in consulting, that once symptoms
      are perceived, women have a higher propensity to consult a general practitioner
      with the symptom than men.

PMID- 9541076
TI  - The social construction of the breast cancer epidemic.
AB  - The age-adjusted incidence of breast cancer among U.S. women rose by over 30%
      during the 1980s. Several population-based studies have concluded that most or
      all of this observed increase is an artifact of the lead time afforded by
      mammography screening rather than an indication of a true increase in the rate at
      which women develop the disease. We conducted a study of the social construction
      of breast cancer trends as a public health problem in popular U.S. magazines. We
      documented trends in popular magazine article coverage of breast cancer between
      1980 and 1995. In addition, we analyzed the content of a convenience sample of
      228 popular magazine articles published between 1987 and 1995, focusing on a
      subsample of articles (n = 91) that mention the increase in breast cancer
      incidence. Our results show that the increase in incidence is commonly portrayed
      as a mysterious, unexplained epidemic occurring primarily among young,
      professional women in their prime years. Many articles suggest that recent
      changes in women's behavior such as increases in delayed childbearing,
      nulliparity, the use of oral contraceptives, induced abortion, and the use of
      tobacco and alcohol are related to the recent upsurge in the disease. The
      portrayal of the breast cancer epidemic in the U.S. popular press reflects a
      strong social desire to create order and control over a frightening disease. In
      the process, a common message is that the behaviors and choices of young,
      nontraditional women especially those related to fertility control-have led to
      pathological repercussions within their bodies, which in turn may be responsible
      for great disorder and pathology at the societal level in the epidemic of breast
      cancer.

PMID- 9541077
TI  - Knowledge and information about ADHD: evidence of cultural differences among
      African-American and white parents.
AB  - Attention deficit hyperactivity disorder (ADHD) is considered the most common
      child psychiatric disorder in the United States of America. Despite the high
      prevalence (estimated at 3-5%), little is known about the level and source of
      knowledge about ADHD among those affected by the disease, and about cultural and
      ethnic variations in knowledge levels and information sources. This represents a
      serious deficit, because health behavior, including demand for health services,
      is thought to be strongly influenced by knowledge or beliefs held by individuals
      and their networks. Furthermore, recent research suggested minority children may
      be less likely to receive services for ADHD. To examine possible differences in
      ADHD knowledge and information source, a sample of 486 African-American and white
      parents of children at high risk for ADHD were surveyed by telephone and
      subsequently participated in face-to-face interviews addressing their explanatory
      models of ADHD. Results revealed significant ethnic differences in knowledge and
      sources of information about ADHD. Fewer African-American parents than white
      parents indicated that they had ever heard of ADHD (69% compared to 95%, P <
      0.001), or that they knew some or a lot about it (36% compared to 70%, P < 0.001)
      African-American parents were more likely to attribute ADHD to excessive sugar in
      the diet than whites (59% compared to 30.0%, P < 0.001). Finally, even though the
      physician was listed as the most preferred information source for both groups,
      only 17.5% of African-American parents reported they had received information
      about ADHD from the physician compared to 29% of whites (P < 0.01). African
      American parents reported less use of and less preference for written
      informational materials (newspapers, journals, library) than white parents. We
      conclude that substantially more research should be undertaken to examine the
      relationship between ethnicity and ADHD knowledge, to inform culturally
      appropriate education campaigns and to improve access to services for this
      important treatable child mental health condition.

PMID- 9541078
TI  - Can raters consistently evaluate the content of focus groups?
AB  - Focus groups are increasingly being used to provide insights to researchers and
      policy makers. These data complement quantitative approaches to understanding the
      world. Unfortunately, quantitative and qualitative methodologies have often been
      viewed as antithetical, rather than complementary, strategies. While focus groups
      can clearly generate rich information that is unobtainable through other
      quantitative methods, it is important to determine the degree to which different
      raters can consistently extract information from transcripts. Thus, our goal was
      to quantify agreement in the interpretation of transcripts from patient and
      physician focus groups, using decision-making in ischemic heart disease as a
      model. We used data from focus groups with both patients and physicians that
      sought to identify factors affecting diagnostic and treatment decisions in
      ischemic heart disease. Three raters independently reviewed transcribed
      audiotapes from focus groups of patients with ischemic heart disease, as well as
      focus groups of physicians who care for these patients. We found that raters
      could not distinguish between major and minor factors reliably. More troubling,
      however, is that consistency regarding the apparently straightforward judgment as
      to the mere presence or absence of a factor was difficult to achieve. In
      particular, the three raters of each transcript failed to agree on between one
      third and one half of the factors. This reasonably high level of disagreement
      occurred despite the raters: (1) having generated the individual factors
      themselves based upon their reading a random sample of actual transcripts and (2)
      being trained in the use of rating forms (including standard definitions of
      themes). These data suggest that if a single rater evaluates focus group
      transcripts, as is commonly done, judgments may not be reproducible by other
      raters. Moreover, a single rater may not extract all important information
      contained in the transcripts.

PMID- 9541079
TI  - Some reflections on cost-effectiveness analysis.

PMID- 9541080
TI  - Colorectal cancer screening: efficiency and effectiveness.
AB  - The cost-effectiveness of a series of mutually exclusive colorectal cancer
      screening programmes with varying screening interval and target group are
      analysed. Costs and effects for 60 possible screening programmes are simulated on
      the basis of data collected from a randomized trial initiated in 1985 in Funen
      County, Denmark. The screening test applied is the unhydrated Hemoccult-II. The
      analysis identifies six efficient programmes with cost-effectiveness estimates
      ranging from 17000 to 42500 Danish kroner (DKK) per life-year.

PMID- 9541081
TI  - Faecal occult blood screening for colorectal cancer: is it cost-effective?
AB  - Recently published evidence from two large-scale clinical trials conducted in
      England and in Denmark suggests that faecal occult blood screening for colorectal
      cancer significantly reduces mortality. However, before screening can be
      advocated as part of national health policy, its cost-effectiveness must be
      demonstrated. The English screening trial has been the subject of a detailed
      economic evaluation over the past 10 years In this paper, cost-effectiveness
      estimates of screening are presented, based on cost and outcome data combined in
      a mathematical model developed from the trial's clinical findings The estimates
      of cost per quality-adjusted life-year gained from colorectal cancer screening
      show the procedure to be of similar cost-effectiveness to breast cancer screening
      in the short term. Over the longer term, however, the estimates for colorectal
      cancer screening appear superior.

PMID- 9541082
TI  - Willingness to pay for hormone replacement therapy.
AB  - This study addresses the question of willingness to pay (WTP) for hormone
      replacement therapy (HRT) in order to alleviate menopausal symptoms. The woman
      obtains utility from consumption of goods and health. The purchase of a treatment
      is represented as a shift in the health production function during the treatment
      period. The mean WTP for the HRT is estimated using a parametric and a non
      parametric method. The mean WTP based on these two methods is similar in both
      cases and amounts to about SEK 40000 per year. Further, it is shown that the mean
      WTP is above the mean treatment cost of HRT. Finally, the implied WTP per gained
      quality adjusted life year (QALY) is estimated at about SEK 120000 and SEK 160000
      based on the rating scale (RS) and time trade-off (TTO) methods, respectively.

PMID- 9541083
TI  - Health economic assessment of behavioural rehabilitation in chronic low back
      pain: a randomised clinical trial.
AB  - The aim of this cost-effectiveness study was to compare a combined operant
      programme plus cognitive/relaxation programme with an operant programme plus
      attention-control and to compare both programmes with a waiting-list control
      group and with operant rehabilitation provided, as usual, by the same
      rehabilitation centre. One hundred and forty eight patients with chronic low back
      pain were randomly assigned to the different conditions. The economic endpoints
      were the costs of the programme and other health care utilisation, costs for the
      patient, and indirect costs associated with production losses due to low back
      pain. The effects were measured in terms of global assessment of change and
      utilities, using rating scale and standard gamble methods. The 3-year study
      determined that adding a cognitive component to an operant treatment did not lead
      to significant differences in costs and improvement in quality of life when
      compared with the operant treatment alone. Compared with the common individual
      rehabilitation therapy it can be concluded that the same effects can be reached
      at the same or lower costs with a shorter, more intense standardised group
      programme. The operant treatment alone is more effective than providing no
      treatment in the waiting-list control group.

PMID- 9541084
TI  - Casemix-based funding of Northern Territory public hospitals: adjusting for
      severity and socio-economic variations.
AB  - The Northern Territory intends to make use of Australian National Diagnosis
      Related Groups (DRGs) and their cost relativities as the basis for the allocation
      of budgets among public hospitals. The study reported here attempted to assess
      the extent to which there are variations in severity of illness and socio
      economic status which are not adequately explained by DRG alone and, if so, to
      develop a DRG payment adjustment index by use of routinely available data items.
      The investigation was undertaken by use of a database containing all discharges
      between July 1992 and June 1995. Hospital length of stay was used as a proxy for
      cost. Multivariate analysis was undertaken and it was found that several
      variables were associated with cost variations within DRGs. Stepwise multiple
      linear regression was used to develop a model in which 14 variables were able to
      explain 45% of the variations. Index values were subsequently computed from the
      regression model for each of eight categories of admitted patient episodes which
      are the intersections of three binary variables: Aborigine or non-Aborigine,
      rural or urban usual place of residence of the patient and hospital type
      (teaching or other). It is intended that these index values will be used to
      compute differential funding rates for each hospital in the Territory.

PMID- 9541085
TI  - The effect of employment status on private health insurance coverage: 1977 and
      1987.
AB  - Analyzing cross-sectional data from the National Medical Expenditure Survey
      (NMES), we find that the predicted probability of private insurance coverage for
      low-income individuals as a group fell dramatically from 1977 to 1987. The
      results of a decompositional technique show that the relationship between full
      time employment and private insurance has weakened over the period for low-income
      females, but has strengthened for males in this group. While it appears that low
      income females benefit from part-time employment relative to their unemployed
      cohorts, no discernible difference is found in the likelihood of being covered by
      private insurance for part-time and unemployed males. Finally, evidence
      suggesting a weakening over time in the relationship between part-time employment
      and private insurance coverage is found among middle-income females and high
      income males. From a policy perspective, passage of the Health Insurance
      Portability and Accountability Act of 1996 has taken an important first step in
      attempting to lower the number of uninsured, especially among full-time workers.
      Our findings, however, suggest that this legislation may be too limited in scope
      to effectively reach part-time workers presently uninsured.

PMID- 9541086
TI  - The economic costs of illicit drug use in Ontario, 1992.
AB  - The use of illicit drugs causes health and social problems which imply economic
      costs to society. This paper uses the cost-of-illness method, in particular, the
      human-capital approach to estimate the prevalence-based economic costs of illicit
      drug use in Ontario in 1992. This methodology is consistent with international
      guidelines formulated at the 1994 International Symposium on Economic and Social
      Costs of Substance Abuse. The economic cost of illicit drug use is estimated at
      $489.29 million (Canadian dollars) in 1992. Associated with these costs are
      health-related harms: 211 deaths, half of which occur before the age of 35; and
      20 690 days stay in public hospitals.

PMID- 9541087
TI  - Hydroxychloroquine: past, present, future.

PMID- 9541088
TI  - Anti-heparin antibodies: part of the repertoire of anti-endothelial cell
      antibodies (AECA)

PMID- 9541089
TI  - Undifferentiated connective tissue diseases: mixed or muddled?

PMID- 9541090
TI  - The Eleventh Autoimmune Conference in honor of GRV Hughes and MD Kazatchkine, Tel
      Aviv, Israel, 26 March, 1997.

PMID- 9541091
TI  - A long-term study of hydroxychloroquine withdrawal on exacerbations in systemic
      lupus erythematosus. The Canadian Hydroxychloroquine Study Group.
AB  - The ability of antimalarials to moderate severe disease activity in systemic
      lupus erythematosus (SLE) is plausible but undemonstrated. We evaluated the long
      term effectiveness of maintaining treatment with hydroxychloroquine sulphate
      (HCQ) to prevent major flares in quiescent SLE. Forty-seven patients with
      quiescent SLE who had been randomized to take HCQ (n = 25) or placebo (n = 22) as
      part of a 24-week withdrawal trial were evaluated for an additional 3 years. The
      primary outcome was time to a major flare of SLE which resulted in either the
      institution of or an increase in the current dosage of prednisone of 10 mg/day or
      more, or institution of therapy with immunosuppressive agents. Secondary outcomes
      included the specific subtype of these major flares (glomerulonephritis,
      vasculitis or other) and hospitalization for an exacerbation of SLE. An intent-to
      treat analysis was conducted. Over the 42 months of study, 11 of 22 (50%)
      patients randomized initially to placebo, and seven of 25 (28%) patients
      randomized to continue treatment experienced a major flare. The relative risk of
      major flare for those randomized to continue HCQ compared with controls was 0.43
      (95% CI: 0.17, 1.12). The relative risks for subtypes of flares were 0.26 (95%
      CI: 0.03, 2.54) for nephritis, 0.51 (95% CI: 0.09, 3.08) for vasculitis and 0.65
      (95% CI: 0.17, 2.41) for flares characterized by other symptoms. The relative
      risk of hospitalization for major flare for patients randomized to continue
      hydroxychloroquine was 0.58 (95% CI: 0.13, 2.60). While the results are not
      statistically significant, they are compatible with the clinical belief that HCQ
      has a long-term protective effect against major disease flares in SLE and suggest
      that on average, HCQ use reduces major flares by 57% (95% CI: 83% reduction to
      12% increase).

PMID- 9541092
TI  - Two populations of endothelial cell antibodies cross-react with heparin.
AB  - As endothelial cells (EC) express heparin-like glycosaminoglycans, such as
      heparan sulfate, it was essential to investigate the relation of anti-EC antibody
      (AECA) to heparin reactivity. AECA were detected in 43 of 131 autoimmune sera and
      anti-heparin antibodies (AHA) in 25. These autoimmune reactivities were
      significantly associated (P corrected < 0.0005). Seven AECA-positive/AHA-positive
      and three AECA-negative/AHA-positive sera were affinity-purified using protein G
      column followed by a heparin-Sepharose column. Two populations of AECA were
      recovered from the second column. One was eluted with 0.4 M NaCl which bound to
      EC and to solid-phase heparin with low affinity, but not to soluble heparin. The
      second population of AECA, which was eluted with 4 M guanidine HCl/2 M NaCl,
      recognized EC and solid-phase heparin with high affinity, but also soluble
      heparin. The latter population of AECA might thus be an important cause of
      autoimmune vascular thrombosis in systemic diseases.

PMID- 9541094
TI  - Impact of disease activity and cumulative damage on the health of lupus patients.
AB  - To test if lupus activity and damage predict physical function and general health
      in lupus was the objective of this study. Ninety-six patients with lupus were
      seen at baseline and monthly for 4 months. Sociodemographic characteristics and
      lupus damage (SLICC/ACR DI), were collected at baseline while lupus activity
      (SLAM-R, SLEDAI), health status measures (HAQ, SF-36) and immunological tests
      were collected at each visit. Associations of lupus activity and damage with
      general health and physical function were evaluated. Baseline health status
      measures were greatly impaired and comparable to those of severe medical
      illnesses. In cross-sectional analyses, baseline activity score measured by SLAM
      R, but not by SLEDAI, correlated with most subscales of SF-36. Baseline damage
      score SLICC/ACR DI correlated only with the HAQ and the physical function
      subscale of SF-36. Differences in both activity measures (SLAM-R and SLEDAI) over
      time correlated with change in health status measures while baseline cumulative
      damage (SLICC/ACR DI) correlated with the average level of physical function
      only. Lupus activity measures, SLAM-R and SLEDAI, although differing cross
      sectionally, both reflected patients' health status performance over time and
      lupus damage measure, SLICC/ACR DI, performed well in assessing physical
      function. Lupus patients scores for health are poor and comparable to those found
      in severe medical illnesses.

PMID- 9541095
TI  - Enhancement of hydroxyl radical DNA cleavage by serum anti-dsDNA antibodies in
      SLE.
AB  - Autoantibodies reactive with double-stranded (ds) DNA are a hallmark of systemic
      lupus erythematosus (SLE), but it is not fully elucidated how these antibodies
      contribute to the various pathological changes observed in lupus patients. In a
      previous study, we have found a significant enhancement effect of two murine
      monoclonal anti-dsDNA antibodies on DNA cleavage by the hydroxyl radical. We have
      extended this study and have found that purified polyclonal anti-dsDNA antibodies
      from sera of lupus patients and an MRL/lpr mouse, but not anti-ssDNA antibodies,
      also enhanced radical cleavage of DNA. The cleavage was inhibited by EDTA, DMSO
      and thiourea. The antibody preparations per se did not cleave DNA. These results
      suggest that such an enhancement effect on DNA cleavage is a feature of a
      significant part of anti-dsDNA antibody population and a possible clue in
      understanding the roles of anti-dsDNA antibodies in the pathophysiology of SLE
      under certain circumstances.

PMID- 9541093
TI  - Undifferentiated connective tissue diseases: the clinical and serological
      profiles of 91 patients followed for at least 1 year.
AB  - The objective of this work was to evaluate the clinical and serological profiles
      of patients with undifferentiated connective tissue diseases (UCTD) who had been
      followed for at least 1 year. The retrospective analysis (197495) was based on
      UCTD patients diagnosed on the basis of clinical manifestations suggestive of a
      connective tissue disease, and the presence of at least one non-organ-specific
      autoantibody. A total of 91 patients were evaluated. The condition of 79 remained
      stable during the follow up, while in 12 the UCTD evolved to systemic lupus
      erythematosus (SLE) within a mean period of 3 years (min. 1 year, max. 8 years,
      median 2 years) after the onset of the disease. At baseline none of the
      variables, considered alone, showed an association with the future development of
      SLE. Multiple regression analysis, however, suggested that the association of
      sicca symptoms, Raynaud's phenomenon and/or photosensitivity was inversely
      correlated with the development of SLE (P = 0.0012, Fisher's exact test). The
      most common clinical manifestations of UCTD included arthritis, arthralgias,
      Raynaud's phenomenon, xerostomia, xerophthalmia and leukopenia. The stable UCTD
      patients showed a simple autoantibody profile characterized by a single
      autoantibody specificity in 82% of the cases 30% with anti-Ro/SSA alone and 28%
      with anti-RNP alone. This profile remained stable during the follow up. Anti-RNP
      antibodies alone correlated with the presence of Raynaud's phenomenon and
      arthritis (P < 0.001 and P < 0.01, respectively), while anti-Ro/SSA antibodies
      alone correlated with xerostomia and xerophthalmia (P < 0.01). In conclusion, the
      UCTDs in most of our patients seem to represent distinct clinical entities with a
      limited autoimmune repertoire rather than the early phases of definite connective
      tissue diseases. They could therefore provide an ideal model for the study of the
      clinico-serological correlations in autoimmune diseases.

PMID- 9541096
TI  - High levels of circulating early apoptic peripheral blood mononuclear cells in
      systemic lupus erythematosus.
AB  - Increased in vitro apoptosis and altered expression of apoptosis-related
      molecules have been reported in systemic lupus erythematosus (SLE). It was
      speculated that autoantigens released from apoptizing cells may contribute to the
      etiopathogenesis of SLE by both activation of autoreactive lymphocytes and the
      formation of immune complexes. Conflicting data about the level of cellular
      apoptosis from animal models for SLE and human SLE indicate different
      pathomechanisms. In the present study we analysed the count of circulating early
      apoptotic cells and its correlation with the clinical activity in SLE compared
      with the amount in primary systemic vasculitis (PSV). The percentage of early
      apoptotic cells determined by Annexin V-FITC binding cells was significantly
      increased in peripheral blood of SLE patients compared with normal healthy donors
      (NHD) and PSV (NHD 5.62%, SLE 13.68%, PSV 8.69%). Analysis of lymphocytes
      revealed significantly increased counts in the T cell populations (NHD 5.15%, SLE
      12.22%, PSV 10.01%), whereas the increase in B cells did not reach significance
      level (NHD 9.20%, SLE 18.95%, PSV 16.59%). Apoptotic cell count revealed no
      correlation to SLAM-Score or to immunosuppressive therapy, corticosteroid-dosage
      or absolute lymphocyte count. The general increase of circulating apoptotic cells
      may indicate an impaired clearance in SLE patients, independent of clinical
      activity or therapeutic interventions. Autoantigens from apoptotic cells may
      contribute to both activation of autoreactive lymphocytes and formation of immune
      complexes.

PMID- 9541097
TI  - Cerebral magnetic resonance imaging in patients with or without antiphospholipid
      antibodies.
AB  - OBJECTIVE: To determine in patients with systemic lupus erythematosus (SLE) or
      with primary antiphospholipid syndrome (PAPS) the prevalence of cerebral magnetic
      resonance imaging changes (MRI) and the relationship with antiphospholipid
      antibodies. METHODS: Twenty-nine consecutive SLE patients, 24 PAPS patients and
      31 healthy controls were prospectively included in the study and underwent MRI
      Scan over a 1-year period. MRI scans were analyzed separately by a
      neuroradiologist for white matter changes [periventricular hyperintensity (PVH)
      (0-6 scale), deep white matter hyperintensity (WMH) (0-24 scale)], and one
      neurologist for cerebral atrophy (0-39 scale) and stroke subtypes. Statistical
      assessment consisted of a discriminant analysis performed with SAS-package with
      MRI data as dependent variables and, as independent variables, age, sex, arterial
      hypertension, diabetes mellitus, cardiopathy, migraine, neurological symptoms,
      antiphospholipid antibodies, SLE, steroid treatment. RESULTS: The prevalence of
      cerebral atrophy was increased in both SLE and PAPS groups relative to controls.
      PVH and WMH scores were significantly higher in SLE and PAPS than in controls.
      Focal infarct did not differ in the SLE group when compared with PAPS. PVH and
      WMH scores were significantly higher in patients with neurological symptoms.
      Using a correlation test we found a weak significant correlation between cerebral
      atrophy and lupus anticoagulant. The multivariate analysis found only three
      independent variables related to PVH and WMH: age, the diagnosis of SLE and
      cerebral atrophy. CONCLUSIONS: Age, presence of SLE and presence of neurological
      symptoms were independently related with WMH and PVH, but not antiphospholipid
      antibodies.

PMID- 9541098
TI  - Relapsing polychondritis presenting with recurrent venous thrombosis in
      association with anticardiolipin antibody.
AB  - We describe a case of relapsing polychondritis with recurrent venous thrombosis
      associated with detectable anticardiolipin antibody. This association has not
      been previously reported, although venous and arterial thrombosis has been
      recognized in association with relapsing polychondritis.

PMID- 9541099
TI  - Recurrence risks in mental retardation.
AB  - Despite improvements in diagnostic techniques and progress made in mapping genes
      associated with syndromal mental handicap, the estimation of recurrence risks in
      non-syndromal mental retardation is still dependent on empirical data.
      Unfortunately, few studies are available to guide the clinician and their results
      differ significantly. For example, recurrence risks to all sibs of a male index
      patient with severe mental retardation vary between 3.5% and 14% in commonly
      quoted series. The present review highlights the problems involved in
      interpreting the previous work in this area and discusses the definition of
      mental retardation according to the degree of severity, phenotype, and its
      pattern of inheritance. In planning future studies, an appreciation of these
      issues should allow us to derive accurate and comparable risk figures for use in
      counselling affected subjects and their families.

PMID- 9541100
TI  - Counselling issues in familial hypertrophic cardiomyopathy.
AB  - To illustrate the variable clinical presentations and rates of progression in
      familial hypertrophic cardiomyopathy (FHC), phenotypes and genotypes were
      compared in three FHC families with different genetic defects. In the first
      family, the FHC abnormality was a protein truncating mutation (Gln969X) in the
      cardiac myosin binding protein C gene. The second family had a missense change
      (Asn755Lys) in the same gene. A missense mutation (Arg453Cys) in the cardiac beta
      myosin heavy chain gene was present in the third family. Penetrance associated
      with the Gln969X defect was 27% in the age range 0 to 40 years. This was
      considerably less than the 93% penetrance (0 to 40 years) observed in the two
      families with missense mutations. The variable penetrance in FHC, as well as the
      unpredictability of sudden cardiac death, complicates clinical diagnosis and
      management, including genetic counselling. Although a genetic disease with a
      predominantly adult onset, there are counselling issues in FHC which set it aside
      from other adult onset disorders.

PMID- 9541101
TI  - How the magnitude of clinical severity and recurrence risk affects reproductive
      decisions in adult males with different forms of progressive muscular dystrophy.
AB  - The reproductive history of 177 male patients affected with Becker (BMD) (n=69),
      limb-girdle (LGMD) (n=54), and facioscapulohumeral (FSHMD) (n=54) muscular
      dystrophy (MD) was analysed according to severity of the disease (BMD>LGMD>FSHMD)
      and magnitude of recurrence risk (RR) (high for FSHMD, intermediate for BMD, and
      low for LGMD). Additionally, 62 male patients were interviewed on psychosocial
      issues, in order to disentangle the factors influencing reproductive decisions
      among patients affected with MD. Among male adults, significantly more FSHMD than
      LGMD or BMD patients were married and had children. Age specific reproductive
      outcome was 0.31-0.32 for BMD, 0.51-0.62 for LGMD, and 0.58-1.02 for FSHMD,
      reflecting the influence of the disease's severity. High RRs did not
      significantly diminish reproduction after genetic counselling or correlate with
      less prospective desire for children. Instead, early onset, severity of the
      disease, and past reproductive history were found to diminish reproductive
      outcome after genetic counselling, and prospective family planning was also found
      to be influenced by past reproductive history as well as by emotional/sexual
      dysfunction with the opposite sex.

PMID- 9541102
TI  - Genetic heterogeneity and HOMOG analysis in British malignant hyperthermia
      families.
AB  - Malignant hyperthermia (MH) is an autosomal dominant genetic condition that
      presents in susceptible people undergoing general anaesthesia. The clinical
      disorder is a major cause of anaesthetic morbidity and mortality. The UK
      Malignant Hyperthermia Group has performed genetic linkage analysis on 20 large,
      well defined malignant hyperthermia families, using hypervariable markers on
      chromosome 19q13.1, including the candidate MH gene RYR1, the gene coding for the
      skeletal muscle ryanodine receptor protein. The results were analysed using
      LINKAGE to perform two point and multipoint lod scores, then HOMOG to calculate
      levels of heterogeneity. The results clearly showed genetic heterogeneity between
      MH families; nine of the families gave results entirely consistent with linkage
      to the region around RYR1 while the same region was clearly excluded in three
      families. In the remaining eight MHS families there were single recombinant
      events between RYR1 and MH susceptibility. HOMOG analysis was of little added
      benefit in determining the likelihood of linkage to RYR1 in these families. This
      confirmation of the presence of heterogeneity in the UK MH population, along with
      the possibility of the presence of two MH genes in some pedigrees, indicates that
      it would be premature and potentially dangerous to offer diagnosis of MH by DNA
      based methods at this time.

PMID- 9541103
TI  - Further refinement of Pendred syndrome locus by homozygosity analysis to a 0.8 cM
      interval flanked by D7S496 and D7S2425.
AB  - Pendred syndrome is an autosomal recessive disease characterised by congenital
      sensorineural deafness and goitre. The gene responsible for Pendred syndrome has
      been mapped to chromosome 7q31 in a 5.5 centimorgan (cM) interval flanked by
      D7S501 and D7S523. This interval was recently refined a to 1.7 cM interval
      located between D7S501 and D7S692. In the present study, we report linkage
      analysis data on a large consanguineous family genotyped with eight
      microsatellite markers located between D7S501 and D7S523. Complete cosegregation
      with the disease locus was observed with the loci analysed, which further
      supports locus homogeneity for Pendred syndrome and close linkage to this region.
      Haplotype analysis placed the Pendred syndrome gene between D7S496 and D7S2425 in
      a 0.8 cM interval. This additional refinement of the Pendred syndrome region will
      facilitate the construction of a physical map of the region and will help the
      identification of candidate genes.

PMID- 9541104
TI  - Molecular pathology of familial hypertrophic cardiomyopathy caused by mutations
      in the cardiac myosin binding protein C gene.
AB  - DNA studies in familial hypertrophic cardiomyopathy (FHC) have shown that it is
      caused by mutations in genes coding for proteins which make up the muscle
      sarcomere. The majority of mutations in the FHC genes result from missense
      changes, although one of the most recent genes to be identified (cardiac myosin
      binding protein C gene, MYBPC3) has predominantly DNA mutations which produce
      truncated proteins. Both dominant negative and haploinsufficiency models have
      been proposed to explain the molecular changes in FHC. This study describes two
      Australian families with FHC caused by different mutations in MYBPC3. The first
      produces a de novo Asn755Lys change in a cardiac specific domain of MYBPC3. The
      second is a Gln969X nonsense mutation which results in a truncated protein.
      Neither mutation has previously been found in the MYBPC3 gene. The consequences
      of DNA changes on the function of cardiac myosin binding protein C are discussed
      in relation to current molecular models for this disorder.

PMID- 9541105
TI  - PCR based mutation screening of the laminin alpha2 chain gene (LAMA2):
      application to prenatal diagnosis and search for founder effects in congenital
      muscular dystrophy.
AB  - Classical congenital muscular dystrophy with merosin deficiency is caused by
      mutations in the laminin alpha2 chain gene (LAMA2). Extended sequencing of the
      introns flanking the 64 LAMA2 exons was carried out and, based on these
      sequences, oligonucleotide primers were designed to amplify the coding region of
      each exon separately. By PCR-SSCP analysis, we identified eight new mutations in
      nine families originating from various countries. All induced a premature
      truncation of the protein, either in the short arm or in the globular C-terminal
      domain. A 2 bp deletion in exon 13, 2098delAG, was found in three French non
      consanguineous families and a nonsense mutation of exon 20, Cys967stop, in two
      other non-consanguineous families originating from Italy. Determination of rare
      intragenic polymorphisms permitted us to show evidence of founder effects for
      these two mutations suggesting a remote degree of consanguinity between the
      families. Other, more frequent polymorphisms, G to A 1905 (exon 12), A to G 2848
      (exon 19), A to G 5551 (exon 37), and G to A 6286 (exon 42), were used as
      intragenic markers for prenatal diagnosis. This study provides valuable methods
      for determining the molecular defects in LAMA2 causing merosin deficient
      congenital muscular dystrophy.

PMID- 9541106
TI  - Evidence of linkage of the inflammatory bowel disease susceptibility locus on
      chromosome 16 (IBD1) to ulcerative colitis.
AB  - Crohn's disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases
      (IBD) of unknown aetiology which are characterised by chronic inflammation of the
      gastrointestinal tract. Epidemiological studies suggest the presence of a genetic
      component in the aetiology of both CD and UC. A susceptibility gene for Crohn's
      disease has recently been mapped to the pericentromeric region of chromosome 16
      (IBD1), and this finding has been replicated in two subsequent studies. Although
      CD and UC are distinct clinical entities, the fact that both disorders occur in a
      significant proportion of families with multiple cases of IBD suggests that
      overlapping sets of susceptibility genes may be involved. We have addressed this
      question for IBD1 by typing eight microsatellite markers from the locus in 70
      kindreds affected with either UC only or with both UC and CD and analysing the
      data for linkage by both non-parametric and parametric methods. Evidence for
      linkage was detected in families affected with only UC, with a mean proportion of
      0.70 affected sib pairs sharing alleles identical by descent at D16S3136
      (p=0.01), and a peak non-parametric linkage score of 2.02 at D16S3120 with the
      GENEHUNTER program (p=0.02). The estimated sib relative risk attributable to IBD1
      in these families was 1.46. Surprisingly, no evidence of linkage was detected in
      the families affected with both UC and CD (p>0.2). The data suggest that IBD1 may
      also contribute to susceptibility to ulcerative colitis, and that it is likely to
      be located in the 12 cM interval between D16S419 and D16S409.

PMID- 9541107
TI  - Outcome of chromosomally normal livebirths with increased fetal nuchal
      translucency at 10-14 weeks' gestation.
AB  - The aim of this study was to determine the outcome of chromosomally normal
      livebirths with increased fetal nuchal translucency at 10-14 weeks' gestation.
      Clinical follow up of 89 chromosomally normal livebirths that in fetal life had a
      minimum nuchal translucency thickness of 3.5 mm and a comparison group of 302
      infants whose fetal nuchal translucency thickness at 10-14 weeks of gestation was
      less than 3.5 mm was performed. Major abnormalities, mainly structural defects of
      the cardiovascular or skeletal systems, were found in 10.1% (nine of 89) of the
      group with increased translucency, compared to 2% (five of 302) in those with
      translucency of less than 3.5 mm (chi2=11.9, p<0.001). Delay in achievement of
      developmental milestones was observed in one of the infants with increased
      translucency and in one of the comparison group. The findings of this study show
      that in chromosomally normal fetuses increased nuchal translucency thickness at
      10-14 weeks of gestation is a marker for fetal abnormalities including structural
      defects and genetic syndromes.

PMID- 9541108
TI  - A new strategy for cryptic telomeric translocation screening in patients with
      idiopathic mental retardation.
AB  - Cryptic unbalanced chromosome rearrangements in the telomeric bands of human
      chromosomes constitute a significant cause of "idiopathic" mental retardation.
      Here, we have described a new strategy based upon comparative genomic
      hybridisation (CGH) to screen for these abnormalities. A modified CGH analysis
      showed three unbalanced cryptic rearrangements in five patients from three
      families. These chromosome abnormalities and their balanced forms in the
      relatives were then confirmed by fluorescence in situ hybridisation (FISH). This
      study describes a new approach to the diagnosis of cryptic translocations between
      the G band negative ends of chromosomes and confirms the significant contribution
      of cryptic telomeric rearrangements to idiopathic mental retardation.

PMID- 9541109
TI  - A new approach to the elucidation of complex chromosome rearrangements
      illustrated by a case of Rieger syndrome.
AB  - A patient with a complex chromosome rearrangement and unilateral Rieger syndrome
      is presented. This rearrangement involves four chromosomes and six breakpoints,
      one of which is at 4q25, the candidate region for Rieger syndrome. We discuss a
      novel approach to the elucidation of this case using a multiprobe fluorescence in
      situ hybridisation method to show rearrangements unpredictable from G banded
      analysis, and the clear and unambiguous presentation of the karyotype using
      computer generated colour ideograms.

PMID- 9541110
TI  - Costello syndrome.
AB  - Costello syndrome is characterised by postnatal growth deficiency, coarse facies,
      redundant skin on the neck, palms, soles, and fingers, dark skin, acanthosis
      nigricans, and papillomata. The natural history evolves in two phases, a severe
      failure to thrive during the first months contrasting with a normal weight gain
      in later life. Cardiomyopathy is frequent but other visceral involvement is rare.
      Mild to moderate mental retardation is usual and most patients exhibit a
      characteristic sociable and friendly personality. The pathogenesis and molecular
      basis of the syndrome are unknown and the diagnosis is reliant on clinical
      expertise. Papillomata represent the most characteristic manifestation but may
      arise late in life. The peculiar course of the disease, the typical facies, and
      the ectodermal involvement with loose and hyperpigmented skin are characteristic
      enough to allow an early diagnosis. Most cases have been sporadic, suggesting de
      novo dominant mutations.

PMID- 9541111
TI  - Extensive germinal mosaicism in a family with X linked myotubular myopathy
      simulates genetic heterogeneity.
AB  - A family with two male cousins affected with myotubular myopathy (MTM) was
      referred to us for genetic counselling. Linkage analysis appeared to exclude the
      Xq28 region. As a gene for X linked MTM was recently identified in Xq28, we
      screened the obligatory carrier mothers for mutation. We found a 4 bp deletion in
      exon 4 of the MTM1 gene, which originated from the grandfather of the affected
      children and which was transmitted to three daughters. This illustrates the
      importance of mutation detection to avoid pitfalls in linkage analysis that may
      be caused by such cases of germinal mosaicism.

PMID- 9541112
TI  - Molecular basis of variegate porphyria: a missense mutation in the
      protoporphyrinogen oxidase gene.
AB  - Variegate porphyria (VP) is an autosomal dominant disorder characterised by a
      partial defect in the activity of protoporphyrinogen oxidase (PPO), and has
      recently been genetically linked to the PPO gene on chromosome 1q22-23 (Z=6.62).
      In this study, we identified a mutation in the PPO gene in a patient with VP and
      two unaffected family members. The mutation consisted of a previously unreported
      T to C transition in exon 13 of the PPO gene, resulting in the substitution of a
      polar serine by a non-polar proline (S450P). This serine residue is
      evolutionarily highly conserved in man, mouse, and Bacillus subtilis, attesting
      to the importance of this residue. Interestingly, the gene for Gardner's syndrome
      (FAP) also segregates in this family, independently of the VP mutation. Gardner's
      syndrome or familial adenomatous polyposis (FAP) is also an autosomal dominantly
      inherited genodermatosis, and typically presents with colorectal cancer in early
      adult life secondary to extensive adenomatous polyps of the colon. The specific
      gene on chromosome 5 that is the site of the mutation in this disorder is known
      as APC (adenomatous polyposis coli), and the gene has been genetically linked to
      the region of 5q22.

PMID- 9541114
TI  - The first de novo mutation of the connexin 32 gene associated with X linked
      Charcot-Marie-Tooth disease.
AB  - X linked Charcot-Marie-Tooth disease (CMTX) is a hereditary motor and sensory
      neuropathy caused by mutations in the connexin 32 gene (Cx32). Using the SSCP
      technique and direct sequencing of PCR amplified genomic DNA fragments of the
      Cx32 gene from a Moroccan patient and her relatives, we identified the first de
      novo mutation of the Cx32 gene, consisting of a deletion of a G residue at
      position 499 in the Cx32 open reading frame. This previously unreported mutation
      produces a frameshift at position 147 in the protein and introduces a premature
      stop codon (TAG) at nucleotide 643, which results in the production of a
      truncated Cx32 molecule. This mutation illustrates the risk of an erroneous
      diagnosis of autosomal recessive CMT, especially in populations where
      consanguineous unions are frequent, and its consequences for genetic counselling,
      which can be avoided by molecular analysis.

PMID- 9541113
TI  - Septo-optic dysplasia and WS1 in the proband of a WS1 family segregating for a
      novel mutation in PAX3 exon 7.
AB  - A four generation family (UoM1) was ascertained with Waardenburg syndrome type 1
      (WS1). The proband exhibited both WS1 and septo-optic dysplasia. A G to C
      transversion was identified in PAX3 exon 7 in four subjects affected with WS1 in
      this family including the proband. This glutamine to histidine missense mutation
      at position 391 may also affect splicing. There are over 50 mutations
      characterised in PAX3 in WS1 patients; however, this is the first example of a
      WS1 mutation in exon 7 of PAX3.

PMID- 9541115
TI  - Identification of a new missense mutation in MyBP-C associated with hypertrophic
      cardiomyopathy.
AB  - Hypertrophic cardiomyopathy is a primary cardiac disease, characterised by
      idiopathic myocardial hypertrophy, and is caused by defects in sarcomeric protein
      encoding genes. One of these genes is cardiac myosin binding protein C (MyBP-C),
      in which a number of splice site and duplication mutations causing HCM have been
      described. During mutation screening of a South African HCM population by PCR
      SSCP, a missense mutation, Arg654His, was detected in one proband. Although the
      mutation was present in his three adult children, only the proband himself was
      markedly affected. This is the first report of a disease associated missense
      mutation in MyBP-C which does not affect the myosin or titin binding domains.

PMID- 9541116
TI  - Pancreatic exocrine dysfunction associated with mitochondrial tRNA(Leu)(UUR)
      mutation.
AB  - We report on pancreatic exocrine dysfunction in families that have the
      mitochondrial tRNA(Leu)(UUR) gene mutation. These families exhibited maternally
      inherited diabetes mellitus (DM) and an A to G substitution at nt 3243 of the
      mitochondrial tRNA(Leu)(UUR) gene (A3243G mutation). Pancreatic necropsy samples
      from one proband showed accumulation of degenerated mitochondria in pancreatic
      acinar cells. Pancreatic exocrine dysfunction was recognised by a functional
      pancreatic study. This study indicates that exocrine pancreatic dysfunction may
      be associated with the A3243G mutation.

PMID- 9541117
TI  - Fuch's corneal dystrophy in a patient with mitochondrial DNA mutations.
AB  - A patient with Fuch's corneal dystrophy, sensorineural hearing loss, diabetes,
      cardiac conduction defects, ataxia, and hyperreflexia is described. Analysis of
      lymphocyte mitochondrial DNA showed missense mutations usually associated with
      Leber's hereditary optic neuropathy. The occurrence of Fuch's dystrophy in this
      patient and the biology of corneal endothelial cells suggest that mitochondrial
      defects could be the cause of Fuch's endothelial dystrophy.

PMID- 9541118
TI  - Is meconium ileus genetically determined or associated with a more severe
      evolution of cystic fibrosis?

PMID- 9541119
TI  - UK centres are not following the Royal College of Pathologists' recommendations
      for storage of Guthrie cards: a national policy is needed.

PMID- 9541120
TI  - Cyclopia and sirenomelia in a liveborn infant.

PMID- 9541121
TI  - Chromatographically identified alcohol-induced haemoglobin adducts as markers of
      alcohol abuse among women.
AB  - BACKGROUND: Alcohol-induced changes in haemoglobin have been suggested as
      potential biochemical markers of alcohol abuse. In this study, we investigated
      the diagnostic value of alcohol-induced haemoglobin adducts among women. METHODS:
      Whole (Hb fractions) and affinity-purified (AHb fractions) haemolysates from 87
      women in three groups (a) social drinkers (n=31), (b) heavy drinkers (n=27) and
      (c) alcoholic subjects (n=29) - were analysed by HPLC-CEC. RESULTS: Three
      fractions (HbA 1a2, HbA1dl and AHbA1d1) showed significant differences (P<0.05)
      between the groups and a significant positive correlation (P<0.05) with self
      reported alcohol consumption (r=0.58-0.76) as determined by the Malmo modified
      Michigan Alcoholism Screening Test (MmMAST) and structured CAGE questionnaire
      (r=0.58-0.76). HbA1a2, HbA1d1 and AHbA1d1 had specificities of 97%, 97% and 100%
      respectively and detected 41%, 33% and 78% of heavy drinkers with overall
      accuracies (OAs) of 71%, 67% and 90%. Sensitivities in the detection of alcoholic
      subjects were 86% (OA=92%), 76% (OA=87%) and 81 % (OA=91%) respectively. The
      fractions had higher OAs than traditional markers of alcohol abuse. CONCLUSION:
      This study indicates that at least three alcohol-induced haemoglobin adducts
      occurring in vivo can be measured with promising diagnostic efficiency among
      women.

PMID- 9541122
TI  - Apo E isoforms, insulin output and plasma lipid levels in essential hypertension.
AB  - BACKGROUND: The association between apo E isoforms and insulin output during the
      oral glucose test (OGTT) in 60 non-diabetic, non-obese patients with essential
      hypertension and in control subjects (non-obese, non-diabetic normotensive
      subjects) was estimated. METHODS: According to low or high insulin output during
      OGTT, the subjects were divided into the following groups: normotensive subjects
      with low (NLI) and high (NHI) and hypertensive subjects with low (HLI) and high
      (HHI) insulin output. RESULTS: The apo E 4/2 phenotype was detected in 32% of
      hypertensive subjects but not in control subjects. The frequency of apo E 3/2
      phenotype in hypertensive subjects was 5% and in normotensive subjects 15%. An
      increased frequency of phenotype apo E 4/3 was noticed both in HHI (46%) and in
      NHI (50%) compared with HLI (22%) and NLI (17%) groups. CONCLUSION: The results
      suggest that the determination of phenotypes apo E and insulin output may
      contribute to an early detection of individuals at high risk of hypertension
      development.

PMID- 9541123
TI  - Regulation of gp330/megalin expression by vitamins A and D.
AB  - BACKGROUND: A membrane-bound 550-kD Ca2+-binding glycoprotein belonging to the
      low-density lipoprotein (LDL) receptor superfamily has recently been identified
      as a putative calcium-sensing molecule. This molecule, known as gp330/megalin, is
      among several tissues present in the proximal tubule, parathyroid and placental
      cytotrophoblasts, in which a Ca2+-sensing function has been demonstrated.
      METHODS: Regulation of mRNA and protein expression of gp330/megalin were studied
      in a recently established cell line derived from rat kidney proximal tubule cells
      (IRPTCs), in human JEG-3 cells and in the mouse embryonal carcinoma cell line F9.
      RESULTS: In IRPTCs, quantification of mRNA and protein expression demonstrated
      two- to five-fold increases after addition of 10(-6) mol L(-1) all-trans-retinoic
      acid, 9-cis-retinoic acid or 1,25-dihydroxyvitamin D3, alone or in combination.
      Similarly, an increase in gp330/megalin mRNA expression was seen in JEG-3 cells
      cultured with vitamin D and retinoids, as well as when F9 cells were
      differentiated by incubation with retinoic acid and cAMP. The IRPTCs were
      immortalized by viral infection with the SV40 genome preceded by a temperature
      sensitive promoter. Thus, by culture of the cells at 41 degrees C, SV40 genome
      transcription is inhibited and the IRPTC phenotype is reversed towards non
      infected proximal tubule cells. At 41 degrees C, gp330/megalin mRNA expression
      was significantly increased compared with cells incubated at 34 degrees C.
      CONCLUSION: The results indicate a correlation between exposure to retinoic acid
      or vitamin D or induction of cell differentiation (by retinoic acid/cAMP in F9
      cells or inhibition of SV40 transcription in IRPTCs) and an increase in
      gp330/megalin protein and mRNA expression.

PMID- 9541124
TI  - Measurement of free fatty acid kinetics during non-equilibrium tracer conditions
      in man: implications for the estimation of the rate of appearance of free fatty
      acids.
AB  - BACKGROUND: This study aimed to document the applicability and variability of
      free fatty acid (FFA) kinetic parameters during non-equilibrium and equilibrium
      tracer conditions in man. METHODS: FFA kinetic parameters were assessed after an
      overnight fast in six healthy non-obese and three obese subjects as well as in
      three patients with non-insulin-dependent diabetes mellitus (NIDDM) by infusion
      of [14C]-palmitate of 60 min (study A) and 10 min duration (study B). RESULTS:
      The kinetic parameters estimated from the upstroke and downstroke of the plasma
      FFA specific activity curve (non-equilibrium) were not statistically different
      within studies A and B. Furthermore, there were no significant differences in any
      of the FFA kinetic parameters between studies A and B. The averaged plasma levels
      of FFA obtained during the up- and downstroke from studies A and B were higher in
      obese subjects and NIDDM patients than in non-obese subjects (P < 0.01). The
      averaged total rate of appearance (TRa) of FFA was higher in obese subjects than
      in non-obese subjects (P < 0.02). The TRa and metabolic clearance rate (MCR),
      estimated from non-equilibrium conditions, were about 25% higher than the
      apparent values obtained from steady-state measurement in all subjects combined
      (P < 0.01), suggesting considerable recirculation of label from hydrolysis of
      labelled esterified fatty acids. Indeed, in three non-obese subjects, the
      radiolabel in esterified fatty acids was approximately 50% of labelled FFA at 60
      min of label infusion. The coefficients of variation of the kinetic parameters
      were consistently larger in study A than in study B. CONCLUSION: FFA kinetic
      parameters can be estimated with sufficient precision using non-equilibrium data
      from short-term labelled palmitate infusion. Short-term label infusion has the
      advantage that label recirculation is prevented and exposure to radiation is
      limited.

PMID- 9541125
TI  - Autoantibodies directed against phospholipids or human beta 2-glycoprotein I in
      HIV-seropositive patients: relationship with endothelial activation and
      antimalonic dialdehyde antibodies.
AB  - BACKGROUND: We investigated the possible role of antiphospholipid (APA) and anti
      human 2-glycoprotein I (beta2-GPI) antibodies (Ab) in thrombosis and
      atherosclerosis in human immunodeficiency (HIV)-positive patients, in whom they
      seem to be more frequent. METHODS: We measured APA and anti-beta2-GPI Ab in 58
      HIV-positive patients together with markers of disease progression, circulating
      beta2-GPI, plasma lipids, biological markers of endothelial activation and
      integrity (plasma thrombomodulin, von Willebrand factor, vascular cell adhesion
      molecule 1) and with antimalonic dialdehyde antibodies (anti-MDA Ab). RESULTS: We
      found a 41% frequency of IgG APA in the HIV-positive patients. APA IgMs were
      rarely positive (7%), and anti-beta2-GPI IgGs were positive in 3-4% patients.
      There was no correlation between APA or anti-beta2-GPI Ab and the presence of
      opportunistic infections. Although plasma thrombomodulin, von Willebrand factor
      and vascular cell adhesion molecule 1 were significantly increased in the HIV
      positive patients, APA was correlated only with vascular cell adhesion molecule
      1, suggesting that APAs are correlated with endothelial activation but not with
      vascular endothelial lesions. A correlation between APA and anti-MDA IgG was
      demonstrated using multivariate analysis (r=0.542, P < 0.0001), suggesting a
      relationship between the targets of these antibodies. Finally, IgG APAs are
      frequent in HIV infection but are not correlated with biological markers of
      endothelial injury. CONCLUSION: Our results do not support a role for APA or anti
      beta2-GPI in HIV-associated silent vascular endothelial damage. However, the role
      of these autoantibodies in clinically relevant thrombotic events should be
      investigated in HIV-positive patients.

PMID- 9541126
TI  - Release of peptide YY and inhibition of gastric acid secretion by long-chain and
      medium-chain triglycerides but not by sucrose polyester in men.
AB  - METHODS: In the present study, we have investigated the effects of intraduodenal
      perfusion of long-chain and medium-chain triglycerides and of sucrose polyester
      on the release of peptide YY in healthy men. RESULTS: Perfusion of medium-chain
      triglycerides (180 mmol fatty acids) increased the plasma concentration of
      peptide YY from 7.9 pmol L(-1) (SEM 0.2, n=8) to 10.7 pmol L(-1) (SEM 0.5, n=8),
      whereas perfusion of long-chain triglycerides (180 mmol fatty acids) had a
      significantly greater effect, increasing peptide YY concentration from 8 6 pmol
      L(-1) (SEM 0.2, n=8) to 18.9 pmol L(-1) (SEM 2.4, n=8, P < 0.008). A smaller
      quantity of long-chain triglycerides (90 mmol fatty acids) increased plasma
      concentration of peptide YY from 7.4 pmol L(-1) (SEM 0.4, n=8) to 13.3 pmol L(-1)
      (SEM 1.5, n=8), whereas sucrose polyester (90 mmol fatty acids) did not change
      peptide YY concentration. In a previous study, we investigated gastrin-stimulated
      gastric acid output in response to these treatments. The correlation between
      increases in peptide YY in response to all treatments and the decrease in acid
      output was r=0.72 (n=48, P < 0.0001). These results show that both long-chain and
      medium-chain triglycerides, but not sucrose polyester, stimulate the release of
      peptide YY. CONCLUSION: We speculate that peptide YY may play an important role
      in the inhibition of gastrin-stimulated gastric acid secretion by long-chain and
      medium-chain triglycerides.

PMID- 9541127
TI  - Endogenous dopaminergic activity in Child-Pugh A cirrhosis: potential role in
      renal sodium handling and in the maintenance of clinical compensation.
AB  - BACKGROUND: We studied the main determinants of aldosterone secretion in a group
      of 20 patients with biopsy-proven Child-Pugh A cirrhosis without previous ascites
      or diuretic consumption. METHODS: We evaluated the plasma levels of
      adrenocorticotrophic hormone (ACTH), active renin and aldosterone (both supine at
      07.00 h and after 30 min of upright posture),and active renin and aldosterone
      responses 30 min and 60 min after the administration of metoclopramide, a
      dopamine DA2 antagonist (10 mg e.v.). Nine normal subjects were also submitted to
      the metoclopramide stimulation test. RESULTS: Compared with control subjects, the
      patients showed significantly greater incremental aldosterone responses both 30
      min and 60 min after metoclopramide (+30 min: 157.5+/-73.3 vs. 83.5+/-32.2 pg mL(
      1), P< 0003; +60 min: 142.1+/-87.2 vs. 36.8+/-39.0 pg mL(-1), P < 0-001). We
      found significant positive correlations between amplitude of aldosterone response
      30 min after metoclopramide and 24-h urinary fractional excretion of sodium
      (r=0.61, P < 0.01) and basal morning aldosterone levels (r=0.69, P < 0.001).
      CONCLUSIONS: The higher incremental aldosterone responses observed after
      metoclopramide in cirrhotic patients are expressions of increased dopaminergic
      activity in these patients compared with control subjects. Moreover, the
      correlation we found between the degree of dopaminergic activity and 24-h urinary
      fractional excretion of sodium suggests a role for endogenous dopamine as a
      relevant mediator of natriuresis in cirrhosis, at least in patients with
      compensated disease.

PMID- 9541128
TI  - Augmentation of the number of nucleolar organizer regions in human megakaryocyte
      cell lines after induction of polyploidization by a microtubule inhibitor.
AB  - BACKGROUND: Megakaryocyte polyploidization is an advantageous and regulated
      mechanism that leads to an increase in platelet production. In megakaryocytic
      cell lines, polyploidization can be obtained by using colchicine, an inhibitor of
      the tubulin spindle. The nucleolar organizer regions (AgNORs) are parts of
      nucleolar DNA transcribed into ribosomal RNA and are detected by the silver
      staining technique. Their number is proportional to protein synthesis. RESULTS:
      To estimate protein synthesis in polyploid megakaryocytes, AgNORs are measured in
      three cell lines with megakaryocyte properties (DAMI, HEL and K562) after a 4-day
      culture in the presence or absence of colchicine. The mean number of AgNORs per
      cell was 16+/-4 (mean+/-SEM), 24+/-3 and 14+/-3 for DAMI, HEL and K-562 cell
      lines respectively. The addition of colchicine (10 ng mL[-1]) significantly
      increased the number of AgNORs per cell (DAMI 556%, HEL 338% and K-562 300% of
      controls, P < 0.05 using the t-test). Moreover, the number of nucleoles per cell
      after the addition of colchicine was augmented significantly (DAMI 246%; HEL 237%
      and K-562 148% of controls, P < 0.05 using the t-test). The total protein content
      estimated by Bradford's method increased significantly to 226%, 215% and 304% of
      controls in DAMI, HEL and K562 respectively (P < 005 using the t-test). After
      treatment with colchicine, the endomitotic index (EI) [mean of (log2 DNA content
      expressed in N)-1] measured by flow cytometry (and reflecting ploidy) increased
      to 234%, 255% and 301%, respectively, in DAMI, HEL and K-562 cell lines (P < 0.05
      using the t-test). Concomitantly, the number of AgNORs per unit of DNA increased
      in the DAMI and HEL cell lines (P < 0.05 using the t-test) from 48+/-8 and 39+/
      5, respectively, to 79+/-11 and 61+/-10. In contrast, the number of nucleoles and
      the total protein content per endomitotic index were not affected by colchicine
      (P > 0.05 using the t-test), but the number of nucleoles per endomitotic index of
      DAMI cells was affected. CONCLUSION: The increase in the number of the NORs
      induced by an agent known to stimulate polyploidization of megakaryocytic cell
      lines suggests that polyploidization occurs by a proportional increase in protein
      synthesis per DNA unit.

PMID- 9541129
TI  - Antioxidants inhibit the in vitro production of inflammatory cytokines in Crohn's
      disease and ulcerative colitis.
AB  - BACKGROUND: Modulation of cytokine secretion may be of interest in the treatment
      of Crohn's disease or ulcerative colitis. METHODS: The effect of three
      antioxidants - butylated hydroxyanisol, tetrahydropapaveroline and
      nordihydroguaiaretic acid - on the production of tumour necrosis factor (TNF),
      interleukin (IL) 1, IL-6 and IL-8 (measured by enzyme-linked immunosorbent assay)
      by peripheral mononuclear cells and biopsies of inflamed colonic mucosa from
      inflammatory bowel disease patients were studied. RESULTS: We observed a decrease
      in IL-1 and IL-6 production by peripheral mononuclear cells from inflammatory
      bowel disease patients (approximately 50% of control). The three drugs did not
      decrease IL-6 and IL-8 secretion by colonic biopsies, whereas they did inhibit IL
      1 and, to some degree, TNF production. The cytokine-inhibitory effect of
      antioxidants seems to be more pronounced in ulcerative colitis than in Crohn's
      disease. CONCLUSION: Our results suggest that the studied antioxidants, or
      related compounds, may be of interest in inflammatory bowel disease treatment.

PMID- 9541130
TI  - Bezafibrate down-regulates fibrinogen biosynthesis in human hepatoma HepG2 cells.
AB  - BACKGROUND: Bezafibrate reportedly lowers serum lipids and plasma fibrinogen in
      humans and rats, but the mechanism of this process has still to be clarified. We
      have addressed this problem by investigating the effects of bezafibrate on
      fibrinogen in the human hepatoma HepG2 cell line. METHODS: In cells cultured with
      and without bezafibrate, intra- and extracellular fibrinogen was quantified using
      an enzyme-linked immunosorbent assay (ELISA), and changes in the biosynthesis and
      secretion of bezafibrate were monitored by [35S]-methionine labelling. In
      addition, expression of the corresponding mRNA was investigated by Northern
      blotting. As fibrinogen is an acute-phase protein, HepG2 cells exposed to
      interleukin 6 were also analysed. RESULTS: Bezafibrate decreased fibrinogen
      biosynthesis by about 25%, regardless of whether or not the cultures were also
      exposed to interleukin 6. mRNA was reduced in proportion to the concentration of
      interleukin 6 to which the cells were exposed, but intracellular transport and
      release of the protein were not affected. CONCLUSION: Apparently, bezafibrate
      interferes with the biosynthesis of fibrinogen at the pretranslational level but
      does not affect the export of the protein.

PMID- 9541131
TI  - A functional defect in hereditary haemochromatosis monocytes and monocyte-derived
      macrophages.
AB  - BACKGROUND: Hereditary haemochromatosis (HH) is a disease of the metabolism of
      iron characterized by increased iron absorption and heavy parenchymal iron
      deposition, but with the presence of little iron in the mononuclear phagocytic
      system (MPS). METHODS: To investigate the role of the MPS, the phagocytic ability
      of HH monocytes (MNs) and in vitro monocyte-derived macrophages (MDMs) was
      studied. HH patients with different degrees of iron accumulation were chosen.
      RESULTS: We observed that HH patients' MNs and MDMs have a significantly
      decreased ability to phagocytose rabbit red blood cells (RRBCs) and that HH MNs
      possess a significantly decreased capacity to phagocytose Staphylococcus aureus
      (S. aureus). The decrease in the ability to phagocytose S. aureus, however, was
      kinetic in nature, explaining the absence of increased prevalence of bacterial
      infections among HH patients. Both RRBCs and S. aureus were preopsonized with
      heat-inactivated serum. No alteration in the complement-dependent phagocytosis of
      Cryptococcus neoformans was demonstrated when normal human serum was used. The
      phagocytosis defect was observed in 100% of HH patients and was independent of
      the magnitude of iron overload, age or liver damage, and affected the antibody
      mediated uptake of bacteria and (R)RBCs.

PMID- 9541132
TI  - Sponges (Porifera) model systems to study the shift from immortal to senescent
      somatic cells: the telomerase activity in somatic cells.
AB  - Sponges (Porifera) represent the lowest metazoan phylum, characterized by a
      pronounced plasticity in the determination of cell lineages. In a first approach
      to elucidate the molecular mechanisms controlling the switch from the cell
      lineage with a putative indefinite growth capacity to senescent, somatic cells,
      the activity of the telomerase as an indicator for immortality has been
      determined. The studies were performed with the marine demosponges Suberites
      domuncula and Geodia cydonium. It was found that the activity for the telomerase
      in the tissue of both sponges is high; a quantitative analysis revealed that the
      extract from S. domuncula contained 10.3 TPG units per 5000 cell equivalents and
      the one from G. cydonium 8.3 TPG units; hence the activity reached approximately
      30-20% of the activity seen in telomerase-positive reference cells. In contrast,
      dissociated spherulous cells from G. cydonium, after an incubation period of 24
      h, contained no detectable telomerase activity. From earlier studies it is known
      that isolated sponge cells do not proliferate. Based on these findings it is
      assumed that the separation of the senescent sponge cell lineage from the
      immortal germ/somatic cell lineage is triggered by the loss of contact with cell
      adhesion factors. First evidence is included which suggests that the final
      progress of the senescent, telomerase-negative cells to cell death is caused by
      apoptosis.

PMID- 9541133
TI  - Immune response to a single bout of exercise in young and elderly subjects.
AB  - The purpose of this investigation was to examine alterations in lymphocyte
      proliferation activity and T cell subsets following an acute bout of exercise in
      young and old subjects. Six young (26+/-3 years) and nine old (69+/-5 years) male
      subjects were tested at rest and immediately after 20 min of submaximal exercise
      at 50% peak work capacity. Arterial blood was sampled from an indwelling catheter
      for catecholamine and immunology assays. Peripheral blood lymphocytes were
      isolated for mitogen-induced phytohemagglutinin (PHA) proliferation capacity.
      Lymphocyte subsets were analyzed by dual-labeled flow cytometry. As has been
      shown in previous studies, baseline proliferative responsiveness was
      significantly lower in the old (down 22%) compared to the young subjects. In
      response to submaximal exercise, proliferative responsiveness to PHA increased
      significantly in the young subjects (up 55%), however, for the old subjects this
      response did not differ significantly from resting values (up 18%). The number of
      total lymphocytes, as well as CD4+ and CD8+ T cell subsets, at rest were lower
      for old subjects compared with young. Exercise-induced increases in T cell subset
      populations were similar across age groups. It was concluded that, while having
      lower initial T cell numbers and PHA responsiveness, immunoresponsiveness during
      a single bout of exercise is, in general, maintained in old when compared to
      young individuals.

PMID- 9541134
TI  - A comparative analysis of the proteins between the fibroblasts from Werner's
      syndrome patients and age-matched normal individuals using two-dimensional gel
      electrophoresis.
AB  - Werner's syndrome (WS) is an autosomal recessive disorder causing symptoms of
      premature aging. The fibroblasts of WS patients have a shorter life-span than
      normal fibroblasts. We analyzed the fibroblast proteins from three WS patients
      and from three age-matched normal individuals using two-dimensional gel
      electrophoresis and image processing. The expressions of 12 proteins were shown
      to be augmented or suppressed in WS fibroblasts compared with normal fibroblasts:
      11 of 12 spots on the electrophoresis gel of WS fibroblasts were denser than the
      corresponding spots of normal individual fibroblasts, while the remaining one
      spot was fainter in WS fibroblasts than in normal fibroblasts. The abundance of
      these proteins were compared to those of the corresponding proteins from normal
      fibroblasts at various cell passages in vitro reported in the TMIG-2DPAGE
      database. The result shows that the change in the protein patterns in in vitro
      aging did not necessarily correspond to the change in WS fibroblasts, except for
      three proteins abundant in WS fibroblasts, which increased their abundance during
      in vitro aging. These results suggest that the premature aging process of WS
      fibroblasts shares only part of the in vitro aging process of normal fibroblasts.

PMID- 9541135
TI  - On the degradability and exocytosis of ceroid/lipofuscin in cultured rat cardiac
      myocytes.
AB  - The accumulation of lipofuscin (LF)--a polymeric, electron-dense, autofluorescent
      substance--within postmitotic cells is a characteristic manifestation of aging.
      It is generally believed that LF is undegradable and formed due to peroxidative
      alterations of various macromolecules under intralysosomal autophagic
      degradation. We report here that a short-term exposure of cultured neonatal rat
      cardiac myocytes to the thiol protease-inhibitor leupeptin, causes an
      accumulation of numerous electron-dense autophagic lysosomes within the cells.
      Although very similar to LF by ultrastructure, these inclusions do not display LF
      specific, yellow-orange autofluorescence when excited with blue light. Moreover,
      they rapidly disappear from the cells upon re-establishment of normal culture
      conditions. In contrast, prolonged leupeptin treatment results in an accumulation
      of dense lysosomes that also show LF-typical autofluorescence. This
      autofluorescent material remains in the cells after the end of leupeptin action.
      The results suggest that: (i) a certain amount of time is needed for
      autophagocytosed material to become peroxidized, autofluorescent and
      undegradable, i.e. to acquire properties typical of LF; (ii) protease-inhibition
      by itself does not lead to LF-formation but rather allows the prolonged time
      needed for oxidative modification of autophagocytosed material; (iii) mature LF
      is probably not subjected to either degradation or exocytosis.

PMID- 9541137
TI  - Altered response to stimuli of the AP-1/DNA binding activity in a syndrome of
      precocious ageing (geroderma osteodysplastica hereditaria).
AB  - Cell senescence produces changes in the expression of specific genes, suggesting
      that senescent cells express an altered pattern of transcription factors. Here we
      describe how the DNA binding activity of the activator protein 1(AP-1) complex is
      altered in the fibroblasts of a geroderma osteodysplastica patient in response to
      extracellular stimuli.

PMID- 9541136
TI  - Protein oxidation and enzyme activity decline in old brown Norway rats are
      reduced by dietary restriction.
AB  - The effect of aging and diet restriction (DR) on the activity of creatine kinase
      (CK), glutamine synthetase (GS) and protein carbonyl formation in the cerebellum,
      hippocampus and cortex of male and female brown Norway (BN) rats has been
      investigated. It was demonstrated that CK activity in three different regions of
      the rat brain declines with age by 30%. Age-related decrease of GS activity was
      only 10-13% and did not reach statistical significance. Consistent with
      previously published studies, age-related increase of protein carbonyl content in
      each brain area studied has been observed. Preventive effects of a caloric
      restricted diet on the age-associated protein oxidation and changes of the
      activity of CK and GS in the brain was observed for both aging male and female BN
      rats. DR delayed the accumulation of protein carbonyls. Age-related changes of CK
      activity in rat brain were abrogated by DR. The activity of GS in the brain of
      old rats subjected to the caloric restricted diet was higher than that in the
      brain of young animals fed ad libitum. The results are consistent with the notion
      that DR may relieve age-associated level of oxidative stress and lessen protein
      damage.

PMID- 9541138
TI  - Hypothalamic control of development and aging of the thymus.
AB  - Removal of pituitary gland results in atrophy of the thymus. As the pituitary
      gland is under the control of the hypothalamus, destruction of the anterior
      portion of the hypothalamus (AHTL) is expected to negatively influence the thymic
      function. Contrary to our expectation, the thymus became hypertrophic and the
      serum level of the growth hormone (GH) markedly increased, when the anterior
      portion of the hypothalamus was widely destroyed in rats at 1 month and over. The
      results suggested that AHTL removed the cells secreting GHRIH (growth hormone
      release inhibitory hormone), but not GHRH (growth hormone releasing hormone),
      leading to increased secretion of GH from pituitary gland and thymic hyperplasia.
      In other words, the development and aging of thymus appears to be under the
      balance of the positive (GHRH) and negative (GHRIH) signals of the hypothalamus.
      It is most likely that the positive signal is high just after the birth and
      decreases thereafter with a concomitant increase of the negative signal, leading
      to the onset of thymic atrophy at around puberty.

PMID- 9541139
TI  - Behavior pattern, arterial partial pressure of oxygen, superoxide dismutase,
      micro-blood-flow state and longevity or aging.
AB  - It is believed that the mechanisms of aging or longevity are multifactorial. We
      selected four major postnatal factors to verify the mechanisms of longevity and
      aging. Type B behavior is strongly associated with longevity. The frequency of
      Type B behavior pattern (55.5 vs. 26.6%) was significantly higher while Type A
      behavior pattern (2.4 vs. 5.9%) was much lower in the longevity group compared
      with those in the elderly group (P < 0.01). The decline of arterial partial
      pressure of oxygen (PaO2) might relate to the aging process which was supported
      by two facts: (1) low PaO2 might lead to high frequency of chromosomal
      aberrations, the frequency of chromosomal aberrations was 1.22+/-0.53%, 0.57+/
      0.23% and 0.23+/-0.22% in PaO2 < 75, 75-84 or > or = 85 mmHg groups respectively
      (P < 0.025); (2) the lower the PaO2, the more serious the retina
      arteriosclerosis. Five mean contents of superoxide dismutase (SOD) in
      erythrocytes were 626+/-39, 583+/-56, 556+/-43, 547+/-49 and 557+/-40 microg/gHb
      in different age groups. No significant differences were found in the longevity
      group as compared with those in 40-89 years old age groups (P > 0.05), but a
      significantly lower level was found in the middle rather than the young age group
      (P < 0.05). The studies of thixotropy show that micro-blood-flow state also
      sustains a better condition in the longevity group. We consider Type B behavior
      pattern, a higher PaO2, a better micro-blood-flow and a higher level of SOD of
      erythrocytes may be beneficial for longevity.

PMID- 9541140
TI  - Cell proliferation and ku protein expression in ageing humans.
AB  - Previous studies on DNA repair in ageing have demonstrated increased frequencies
      of single and double strand breaks in lymphocytes from elderly subjects and, as a
      consequence, decreased efficiency in DNA replication. We have investigated the
      relationship between cell proliferation and the nuclear expression of ku protein
      in a human population of 43 subjects of different ages. Ku is an heterodimeric
      protein composed of two subunits of 70 and 80 kDa, which is involved in the early
      steps of DNA damage recognition. In the present study, PBL from subjects of
      different ages were PHA-activated to evaluate the stimulation index and the
      production of Th1- and Th2-type cytokines. Moreover, nuclear extracts were
      obtained from activated lymphocytes to evaluate by a gel retardation assay the
      presence and the functional activity of the heterodimer ku 70/80. Our results
      indicate that ageing affects the mitotic responsiveness and cytokine production
      to a significant extent, but only marginally the expression of ku 70/80. These
      findings suggest that the age-related impairment in DNA repair mechanisms are
      only in part related to the reduced expression of ku protein able to recognize
      DNA damage.

PMID- 9541141
TI  - The relation between lifespan of a species and the number of doublings of its
      cells in culture is an unresolved issue.

PMID- 9541142
TI  - Lack of seasonal variation of symptoms in patients with chronic fatigue syndrome.
AB  - Several of the symptoms involved in chronic fatigue syndrome (CFS) such as
      fatigue, hypersomnia, hyperphagia, weight gain, and mood show seasonal variations
      in the general population. The aim of this study was to investigate whether
      patients with CFS experience seasonal fluctuations in these symptoms as well.
      Seasonal variation of symptoms was assessed in a group of 41 patients with CFS
      and 41 controls closely matched for age, gender, and city of residence.
      Participants were recruited across the US and were asked to complete the Seasonal
      Pattern Assessment Questionnaire (SPAQ) and the Profile of Mood States (POMS).
      CFS patients showed significantly lower scores on multiple SPAQ-derived measures
      as compared with controls. These included seasonal variation in energy, mood,
      appetite, weight, and sleep length. Patients also reported a significantly
      reduced sensitivity toward sunny, dry, and long days than controls. No
      association was noted between intensity of seasonal changes and severity of
      depressive symptoms. Patients with CFS exhibit an abnormally reduced seasonal
      variation in mood and behavior and would not be expected to benefit from light
      therapy.

PMID- 9541143
TI  - Testosterone as a biological marker in psychopathy and alcoholism.
AB  - The aim of the present study was to clarify the relationships between
      testosterone and alcohol abuse, alcohol dependence and specific personality
      characteristics and behaviors in a forensic psychiatric population. Serum levels
      of total testosterone (TT), free testosterone (FT-DPC) and sex hormone-binding
      globulin (SHBG) were determined in 61 male subjects undergoing forensic
      psychiatric examinations. All subjects had been detoxified from drugs and alcohol
      during previous incarceration in jail or hospital. TT and FT-DPC were found to be
      highly correlated (r=0.63, P < 0.0001). High concentrations of TT and SHBG were
      consistently related to type II alcoholism, but not pure alcohol dependence. TT
      and SHBG were also related to antisocial personality disorder. Furthermore, TT
      and SHBG were related to socially deviant behavior, reflected in factor 2 in the
      Psychopathy Checklist (PCL-R). In a multiple regression, FT-DPC was also clearly
      associated with the psychopathy-related scales of the Karolinska Scales of
      Personality (KSP) when age and signs of hepatic damage were kept under control.

PMID- 9541144
TI  - GABAergic function in detoxified heroin addicts: relationship to anxiety
      disorders.
AB  - The function of the GABAergic system was examined in 20 subjects with heroin
      dependence and abuse, 2 months after detoxification, and in 10 healthy
      volunteers, by measuring the growth hormone (GH) response to a challenge with the
      GABA B receptor agonist baclofen. Ten heroin addicts had comorbid anxiety
      disorder (Group A), while the other ten had heroin addiction uncomplicated by
      Axis I and II psychopathologies (Group B). GH responses to baclofen stimulation
      of Group A patients were significantly blunted, while those of Group B subjects
      did not differ from responses of healthy volunteers. Our data show that the
      function of the GABAergic system is impaired only in heroin addicts with comorbid
      anxiety disorders (anxious cluster), suggesting that the GABA system is not
      persistently influenced by prolonged exposure to opioid receptor stimulation.

PMID- 9541145
TI  - 5HT2C CYS23/SER23 polymorphism is not associated with obsessive-compulsive
      disorder.
AB  - A great deal of evidence suggests that a genetic component underlies obsessive
      compulsive disorder (OCD). The response to serotonergic medications and the
      worsening of obsessive symptoms after administration of serotonergic agonists
      indicate that serotonergic mechanisms are involved in OCD. We investigated the
      role of the Cys23Ser mutation of the 5HT2C receptor gene in the etiology of this
      disorder by performing an association study comparing a sample of 109 OCD
      patients with a sample of 107 healthy control subjects. No allelic or genotypic
      association of OCD with the 5HT2C receptor gene mutation was revealed in our
      data. We also extended the association analysis to a subsample of 39 OCD patients
      that had previously been submitted to a challenge test with clomipramine. In the
      subsample of OCD patients that received the challenge with clomipramine, no
      association between the 5HT2C receptor gene mutation and response to the
      challenge test was found. Our results exclude any specific role of the Cys23Ser
      mutation of 5HT2C receptor gene in the etiology of OCD: it seems probable that
      more complex genetic models are needed to explain the involvement of serotonergic
      elements in the etiology of this disorder.

PMID- 9541146
TI  - Immunophenotypic studies on atypical lymphocytes in psychiatric patients.
AB  - By using phase-contrast microscopy combined with a fluorescent staining
      technique, the frequency of blast-type atypical lymphocytes (BTALs) appearing in
      peripheral blood and the phenotypic expression of their surface antigens were
      studied in 24 patients with schizophrenia, 16 with mood disorder and 14 healthy
      controls. BTALs were classified as being stimulated or activated cells,
      morphologically characterized by their large size, dark cytoplasm, a hollow
      perinuclear containing a few granules and finely dispersed chromatin structures
      with a few evident nucleoli. A significantly higher number of BTALs were found in
      the schizophrenic patients compared with healthy control subjects or patients
      with mood disorder. Further, there was a significant difference in the frequency
      of BTALs between patients with mood disorder and healthy control subjects. No
      significant difference in the frequency of BTALs was found between the
      schizophrenic patients with and without medication. Immunostaining of BTALs
      revealed that these cells consisted of B, T and non-B, non-T cell subpopulations.
      Contrary to our expectations, the T cell was only one third of the BTAL
      population. HLA-DR and CD38 were expressed on most BTALs (> 70%), while CD25, an
      early activation marker of T cells was rarely found on BTALs (< 0.3%). The
      differences in activated lymphocyte populations which appeared as morphologically
      atypical in the circulation among some psychiatric patients and infectious or
      autoimmune diseases are discussed. This is the first report on populations of
      BTALs.

PMID- 9541147
TI  - Affect recognition in deficit syndrome schizophrenia.
AB  - This study has three aims: (1) to compare a deficit syndrome schizophrenia sample
      (n=19) with a non-deficit sample (n=50) on affect recognition; (2) to determine
      the association between individual deficit criteria and affect recognition
      performance in the deficit sample; and (3) to compare the deficit syndrome and
      negative syndrome samples with respect to affect recognition test performance.
      Results revealed that the deficit sample had significantly lower adjusted mean
      affect recognition scores than the non-deficit sample. In addition, 17 of the 19
      subjects with deficit syndrome had impairments in affect recognition, whereas,
      non-deficit subjects were only slightly more likely to score in the impaired
      range than the unimpaired range. Within the deficit sample Diminished Sense of
      Purpose was the criterion most strongly associated with affect recognition
      impairment. Finally, a group of subjects classified as having prominent negative
      symptoms did not demonstrate the same pattern of impairment as shown by the
      deficit syndrome sample. The relationship between affect recognition, information
      processing and the deficit syndrome is discussed along with implications for
      classification in schizophrenia.

PMID- 9541148
TI  - Psychopathological dimensions in schizophrenia: a correlational approach to items
      of the SANS and SAPS.
AB  - Seventy DSM-III schizophrenic patients were assessed for positive and negative
      symptoms using Andreasen's scales for the assessment of positive and negative
      symptoms (SANS and SAPS) on admission. The correlation structure of the items in
      the SANS and SAPS was explored in dimension and item levels by use of correlation
      plots through a distinct analytical method displaying the proximity matrix. The
      results revealed at least three major dimensions of symptoms delineated as
      Negative Symptoms, Disorganized Thoughts and Delusions and Hallucinations. The
      latter two dimensions were derived from the SAPS, while Negative Symptoms
      comprised most of the items in the SANS. Items in Disorganized Thoughts were more
      correlated to Negative Symptoms than to the other items in the SAPS. 'Loss of ego
      boundary' delusions and experience of auditory hallucinations appeared as two sub
      clusters in the group of Delusions and Hallucinations. The relative independence
      of persecutory, grandiose, religious, somatic and reference delusions gives
      support to the concept that paranoid schizophrenia stands as a distinct clinical
      subtype of schizophrenia. The graphical method introduced here well expresses the
      information of correlation matrix and is useful for exploring inter-item or inter
      cluster associations.

PMID- 9541149
TI  - Electroencephalographic abnormalities in borderline personality disorder.
AB  - Epilepsy and non-localized brain dysfunction have been invoked, among others, as
      underlying factors in borderline personality disorder. We have recorded 58
      electroencephalograms in 20 borderline patients, first after complete drug
      washout and then under carbamazepine or placebo double-blind treatment. Taking
      into account only definite abnormal tracings, we found a 40% incidence of
      abnormal diffuse slow activity. No patient disclosed focal or epileptiform EEG
      features. Carbamazepine did not appear to modify the electroencephalogram.

PMID- 9541150
TI  - Nitric oxide physiology and pharmacology.

PMID- 9541151
TI  - Low-dose clozapine in acute and continuation treatment of severe borderline
      personality disorder.
AB  - BACKGROUND: Psychotic-like symptoms in patients affected by borderline
      personality disorder (BPD) are usually treated with low-dose neuroleptics, which
      show controversial acute effects and lead to a worsening of affective-related
      symptoms and to severe neurologic side effects after prolonged administration.
      Clozapine lacks the neurologic side effects of traditional neuroleptics and has
      been shown to successfully treat psychotic-like symptoms in BPD patients at
      medium dose. We performed an open-label trial of low-dose clozapine in severe BPD
      patients. METHOD: Twelve BPD inpatients (DSM-IV criteria) with severe psychotic
      like symptoms were studied. Exclusion criteria included comorbid Axis I and
      medical pathologies. All patients had followed a therapeutic program without
      improvement for at least 4 months before admission. The clozapine dose was
      titrated upward on an individual basis until the complete disappearance of
      psychotic-like symptoms was achieved. Clinician-rated scales were completed at
      the beginning of the study and after 4 and 16 weeks. RESULTS: All patients
      completed the 16-week study. Individual clozapine doses ranged from 25 to 100
      mg/day. Psychotic-like symptoms decreased within the first 3 weeks of treatment,
      as confirmed by a statistically significant decrease in Brief Psychiatric Rating
      Scale scores. This amelioration was coupled with an overall improvement,
      including a reduction in impulsive behaviors and in affective-related symptoms
      (Hamilton Rating Scale for Depression) and an increase in global functioning
      (Global Assessment of Functioning). CONCLUSION: Low-dose clozapine for acute and
      continuation treatment led to improvement in overall symptomatology in a small
      sample of severe BPD patients.

PMID- 9541152
TI  - Borderline personality symptomatology, experience of multiple types of trauma,
      and health care utilization among women in a primary care setting.
AB  - BACKGROUND: This project was designed to explore the relationship between
      recollected trauma history, borderline personality symptomatology, and health
      care utilization among women in a primary care setting. METHOD: Women (N = 116)
      consecutively recruited during routine gynecological appointments were given a
      set of questionnaires that explored 5 types of trauma (i.e., sexual, physical,
      and emotional abuse; physical neglect; witnessing violence) as well as borderline
      personality symptomatology. The preceding 12 months of participants' medical
      records were blindly reviewed to determine several measures of health care
      utilization (i.e., number of telephone contacts to the facility, physician
      visits, ongoing and acute prescriptions, specialist referral). RESULTS: Multiple
      forms of trauma were related to increased telephone contacts, physician visits,
      acute prescriptions, and ongoing prescriptions. Borderline personality
      symptomatology was related to physician visits and ongoing prescriptions. Neither
      was related to the number of specialist referrals. Total number of types of
      trauma and borderline personality symptomatology scores were moderately related
      to each other (r = .36, p < .01). CONCLUSION: With the exception of specialist
      referrals, the experience of multiple types of trauma and borderline personality
      symptomatology contribute to higher health care utilization among women in a
      primary care setting, but not to a substantial degree. The experience of trauma
      and borderline personality symptomatology appear partially related to each other.
      This relationship has several implications.

PMID- 9541153
TI  - Bupropion as an antidote for serotonin reuptake inhibitor-induced sexual
      dysfunction.
AB  - BACKGROUND: Serotonin reuptake inhibiting antidepressants (SRIs) are reported to
      cause sexual dysfunctions, including reduction in desire, arousal, and orgasm.
      This study evaluates the efficacy of bupropion in ameliorating sexual
      dysfunctions in patients receiving SRIs. METHOD: Forty-seven patients in an
      outpatient psychiatric practice who complained of SRI-induced sexual dysfunction
      accepted a trial of bupropion as an adjunct to their SRI, either as a p.r.n. or
      as a fixed-dose scheduled medicine. Patients received 75 mg or 150 mg of
      bupropion 1 to 2 hours before sexual activity. If this was insufficient to reduce
      their complaints, dose was increased gradually to 75 mg t.i.d. and sustained for
      2 weeks. This regimen was then continued if successful. RESULTS: Bupropion
      successfully reversed a variety of sexual dysfunctions caused by SRIs in 31 (66%)
      of 47 patients. Fifty-two (69%) of 75 sexual complaints improved with bupropion
      treatment. The p.r.n. use of bupropion assisted 18 (38%) of 47 patients. Side
      effects of anxiety and tremor led to discontinuation of bupropion in 7 (15%) of
      47 patients. Otherwise, bupropion was well tolerated. CONCLUSION: Bupropion
      administration may be a safe and effective method of treating SRI-induced sexual
      dysfunction. Placebo-controlled, double-blind studies are needed.

PMID- 9541154
TI  - A randomized, placebo-controlled, dose-response trial of venlafaxine
      hydrochloride in the treatment of major depression.
AB  - BACKGROUND: We examined the efficacy and safety of three different dosages of
      venlafaxine hydrochloride (75, 225, and 375 mg/day) in a multicenter, randomized,
      double-blind, placebo-controlled, four-group study. METHOD: Outpatients, 18 to 65
      years old, who met DSM-III criteria for major depression were included (N = 358
      randomized; 194 completed). Of the total patients completing the trial, 59%, 56%,
      51%, and 51% were in the placebo, 75-mg, 225-mg, and 375-mg groups, respectively.
      The primary outcome measures were the Hamilton Rating Scale for Depression (HAM
      D21) total, HAM-D21 depression item, Montgomery-Asberg Depression Rating Scale
      total, and Clinical Global Impressions scale. RESULTS: Each dosage of venlafaxine
      was associated with statistically significant improvement as compared with
      placebo, based on the intent-to-treat sample. The two higher dosages were
      associated with a modestly greater antidepressant response than was the 75-mg
      dosage. Nausea, dizziness, somnolence, and anorexia were the most common adverse
      events attributable to venlafaxine. Since headache occurred at a similar
      frequency in both the drug and placebo groups, we did not consider it to be
      attributable to venlafaxine use. Withdrawal from the study due to adverse events
      occurred in 5%, 17%, 24%, and 30% of the patients in the placebo, 75-mg, 225-mg,
      and 375-mg groups, respectively. CONCLUSION: Venlafaxine, at dosages of 75-375
      mg/day, is an effective and well-tolerated antidepressant. With increasing
      dosage, greater efficacy and possibly more adverse effects will occur.

PMID- 9541155
TI  - A meta-analysis of eight randomized, double-blind, controlled clinical trials of
      mirtazapine for the treatment of patients with major depression and symptoms of
      anxiety.
AB  - BACKGROUND: Patients diagnosed with major depression and prominent symptoms of
      anxiety often have a poor prognosis for recovery. A meta-analysis was performed
      to assess the efficacy of mirtazapine in comparison with placebo and
      amitriptyline for the relief of anxiety/agitation or anxiety/somatization in
      patients with major depressive illness. METHOD: A meta-analysis of eight
      randomized, double-blind, placebo-controlled clinical trials was conducted for
      161 mirtazapine-treated and 132 placebo-treated patients with a DSM-III diagnosis
      of major depression, baseline Hamilton Rating Scale for Depression (HAM-D) scores
      > or = 18, and a baseline score > or = 6 for the sum of HAM-D items 9, 10, and 11
      (anxiety/agitation). Four of the clinical trials included an amitriptyline
      control group (N = 92). RESULTS: Mirtazapine-treated patients demonstrated a
      statistically significant (p < or = .05) reduction in the sum of HAM-D items 9,
      10, and 11 (anxiety/agitation) compared with placebo-treated patients at Weeks 1,
      2, 4, and 6 and at the endpoint. There was no statistically significant
      difference between the mirtazapine- and amitriptyline-treated patients at Weeks
      1, 3, 4, 5, and 6 and at the endpoint. Similar results were found for the
      analysis of the mean of HAM-D items 10, 11, 12, 13, 15, 17 (anxiety/somatization
      or HAM-D Factor Score I) using all treated patients with a post-baseline
      evaluation in all 8 studies. Mirtazapine-treated patients demonstrated a
      statistically significant (p < or = .03) greater reduction at Weeks 1-6 compared
      with placebo, and improvement in the mirtazapine group was comparable to
      improvement in the amitriptyline group at Weeks 1-6. CONCLUSION: In this meta
      analysis of eight randomized, double-blind, controlled clinical trials,
      mirtazapine was found to be superior to placebo and comparable to amitriptyline
      for the treatment of patients with major depression with symptoms of
      anxiety/agitation or anxiety/somatization.

PMID- 9541156
TI  - Cocaine as a risk factor for neuroleptic-induced acute dystonia.
AB  - BACKGROUND: A prospective study was conducted to test the hypothesis that cocaine
      use is a risk factor for neuroleptic-induced acute dystonia (NIAD). METHOD: The
      study sample consisted of a high-risk group for NIAD, males aged 17-45 years who
      had received high-potency neuroleptics within 24 hours of admission and had not
      used neuroleptics in the month prior to admission. Patients were excluded if they
      suffered from a neurodegenerative disorder or were exposed to anticholinergics,
      benzodiazepines, promethazine, carbamazepine, phenytoin, or levodopa during the
      study. Twenty-nine patients--9 cocaine users and 20 nonusers--entered the study,
      which lasted 2 years. Patients were followed for 7 days. RESULTS: Cocaine-using
      psychiatric patients developed significantly more NIAD than did nonusers
      (relative risk = 4.4, 95% CI = 1.4 to 13.9). CONCLUSION: Cocaine use is a major
      risk factor for NIAD and should be added to the list of well-known risk factors.
      The authors strongly suggest that cocaine-using psychiatric patients who are
      started on a regimen of neuroleptics should also be administered an
      anticholinergic for at least 7 days to prevent NIAD.

PMID- 9541157
TI  - Rebound psychiatric and physical symptoms after gabapentin discontinuation.

PMID- 9541158
TI  - Elevated plasma clozapine concentrations after phenobarbital discontinuation.

PMID- 9541159
TI  - Can bruxism respond to serotonin reuptake inhibitors?

PMID- 9541160
TI  - Article commended.

PMID- 9541161
TI  - Possible dose-response relationship for risperidone in obsessive-compulsive
      disorder.

PMID- 9541162
TI  - Differences in self-reported sleep complaints in elderly persons living in the
      community who do or do not take sleep medication.
AB  - BACKGROUND: Sleep disorders and the use of sleep medication are major health
      issues. Since complaints about sleep disturbances are subjective phenomena, the
      aim of the present study was to investigate which sleep complaints and self
      reported disturbances of sleep behavior are connected with the utilization of
      sleep medication. METHOD: In the Berlin Aging Study, a random sample of 516
      persons aged 70 to over 100 underwent extensive psychiatric and medical
      examinations including several medication assessments and a special interview on
      sleep complaints and sleep behavior. RESULTS: 19.1% of the elderly were taking
      some form of sleep medication. Univariate and discriminant analyses showed that
      neither self-reported duration of sleep time nor difficulties with sleeping
      through the night but complaints about difficulties initiating sleep and global
      complaints about disturbed sleep differentiated between those who do or do not
      take sleep medication. CONCLUSION: Persons taking sleep medication nevertheless
      have a higher rate of sleep-related complaints than those who take no medication.
      Waking up in the night per se does not discriminate between drug users and
      controls. Instead, it is the inability to fall asleep or fall back into sleep
      after waking and global discontent with subjective sleep quality that make a
      difference.

PMID- 9541163
TI  - Introduction of apoptosis by high proinsulin and glucose in cultured human
      umbilical vein endothelial cells is mediated by reactive oxygen species.
AB  - There is much evidence that diabetes and hyperglycaemia contribute to the
      impairment of endothelial function and induce severe changes in the
      proliferation, the adhesive and synthetic properties of endothelial cells.
      Induction of apoptosis could represent one mechanism to prevent the new
      accumulation of those vascular defects and to allow generation of vascular
      endothelium. In this study, we demonstrate that high concentrations of glucose or
      proinsulin induce apoptosis in human umbilical endothelial cells by three
      independent methods (DNA fragmentation, fluorescence activated cell sorting
      analysis, and morphology). The number of apoptotic cells was increased by glucose
      (30 mmol/l or proinsulin (100 nmol/l) from less than 10% to about 30%. Activation
      of protein kinase C (PKC) largely prevented the induction of apoptosis, whereas
      inhibition of PKC further increased the number of apoptotic cells. Similar
      changes as induced by glucose were also observed after incubation of the cells
      with the non-metabolisable 3-O-methylglucose. These findings indicate that
      hyperglycaemic conditions stimulate the induction of apoptosis in endothelial
      cells by a mechanism which is independent from the formation of diacylglycerol
      and the activation of PKC. The induction of apoptosis by the non-metabolisable
      glucose suggests that formation of oxygen derived radicals by autoxidative
      processes is involved and may lead to an activation of transcription factors such
      as nuclear transcription factor-kappaB (NF-kappaB) transferring the activation
      signal into the nucleus and leading to changes in gene expression necessary for
      induction of apoptosis.

PMID- 9541164
TI  - Pioglitazone time-dependently reduces tumour necrosis factor-alpha level in
      muscle and improves metabolic abnormalities in Wistar fatty rats.
AB  - In order to evaluate the relationship between tumour necrosis factor-alpha (TNF
      alpha) level in muscle and metabolic abnormalities in obesity and diabetes
      mellitus, pioglitazone, a novel insulin-sensitizing agent, was administered to
      Wistar fatty rats and time-dependent changes in muscle TNF-alpha content and
      plasma indicators of diabetes and obesity were measured. Wistar fatty rats were
      hyperglycaemic, hyperlipidaemic and hyperinsulinaemic, and their plasma and
      muscle TNF-alpha levels were two or more times higher than those in normal lean
      rats at 16 weeks of age. When pioglitazone was administered to fatty rats at a
      dose of 3 mg kg(-1) day(-1), the plasma triglyceride level and TNF-alpha levels
      in plasma and muscle decreased time-dependently, and reached the levels of lean
      rats within 4 days. Plasma glucose and insulin levels also decreased time
      dependently with pioglitazone, but on day 4, these levels were still much higher
      than the levels in lean rats. Neutral sphingomyelinase (SMase) activity in muscle
      of fatty rats was two times higher than that in lean rats and was lowered to the
      level of that in lean rats by 4 days' pioglitazone administration. The plasma
      leptin level in fatty rats was 8 times higher than that in lean rats, but
      pioglitazone did not affect the level during the 4-day administration period.
      These results suggest that an increase in TNF-alpha production and subsequent
      activation of SMase in muscle leads to metabolic abnormalities in obesity and
      diabetes and that antidiabetic activity of pioglitazone is deeply associated with
      the suppression of TNF-alpha production.

PMID- 9541165
TI  - Immunological evidence for increased oxidative stress in diabetic rats.
AB  - The role of oxidative stress in aging and diabetes mellitus is currently under
      discussion. We previously showed age-dependent accumulations of fluorescent
      protein adducts with lipoperoxidative aldehydes, (malondialdehyde (MDA), and
      hydroxynonenal (HNE)) in rat skin collagen with diabetic BB rats exhibiting
      faster accumulation. Modified proteins have been shown to be immunogenic:
      antibody titres against rat serum albumin modified by MDA and HNE (MDA-RSA and
      HNE-RSA) or oxidized by reactive oxygen species were measured by ELISA as markers
      of oxidative damage in BB diabetic and non-diabetic rats. Each tested antibody
      titre was significantly higher in the diabetic than in the non-diabetic rats. A
      significant correlation existed between anti-MDA-RSA and anti-HNE-RSA antibody
      titers. Only the anti-HNE-RSA antibody titre increased significantly with age
      (p=0.052) in diabetic animals, while no titres increased significantly in non
      diabetic animals. A major factor which correlated with the development of these
      antibodies was diabetes duration: this was significant (p=0.032) for anti-HNE-RSA
      antibody titre and slightly significant (p=0.05) for anti-MDA-RSA antibody titre.
      Thus, chronic hyperglycaemia is probably fundamental in the increase of oxidative
      stress. There is correlation between anti-aldehyde-RSA antibody titres and the
      corresponding aldehyde-related collagen-linked fluorescence: modified collagen
      may play a part in the observed immune response. Our data indicate a stronger
      immune response of diabetic rats against proteins modified by lipoperoxidative
      aldehydes and oxygen free radicals, and they support the hypothesis of increased
      oxidative damage in diabetes.

PMID- 9541166
TI  - Dipeptidyl peptidase IV resistant analogues of glucagon-like peptide-1 which have
      extended metabolic stability and improved biological activity.
AB  - Glucagon-like peptide 1 (GLP-1) has great potential in diabetes therapy due to
      its glucose-dependent stimulation of insulin secretion, but this is limited by
      its rapid degradation, primarily by dipeptidyl peptidase IV. Four analogues, N
      terminally substituted with threonine, glycine, serine or alpha-aminoisobutyric
      acid, were synthesised and tested for metabolic stability. All were more
      resistant to dipeptidyl peptidase IV in porcine plasma in vitro, ranging from a
      t1/2 of 159 min (Gly8 analogue) to undetectable degradation after 6 h (Aib8
      analogue; t1/2 for GLP-1 (7-36) amide, 28 min). During i. v. infusion in
      anaesthetised pigs, over 50% of each analogue remained undegraded compared to
      22.7 % for GLP-1 (7-36) amide. In vivo, analogues had longer N-terminal t1/2
      (intact peptides: means, 3.3-3.9 min) than GLP-1 (7-36) amide (0.9 min; p <
      0.01), but these did not exceed the C-terminal t1/2 (intact plus metabolite:
      analogues, 3.5-4.4 min; GLP-1 (7-36) amide, 4.1 min). Analogues were assessed for
      receptor binding using a cell line expressing the cloned receptor, and for
      ability to stimulate insulin or inhibit glucagon secretion from the isolated
      perfused porcine pancreas. All bound to the receptor, but only the Aib8 and Gly8
      analogues had similar affinities to GLP-1 (7-36) amide (IC50; Aib8=0.45 nmol/l;
      Gly8=2.8 nmol/l; GLP-1 (7-36) amide=0.78 nmol/l). All analogues were active in
      the isolated pancreas, with the potency order reflecting receptor affinities
      (Aib8 > Gly8 > Ser8 > Thr8). N-terminal modification of GLP-1 confers resistance
      to dipeptidyl peptidase IV degradation. Such analogues are biologically active
      and have prolonged metabolic stability in vivo, which, if associated with greater
      potency and duration of action, may help to realise the potential of GLP-1 in
      diabetes therapy.

PMID- 9541168
TI  - Differential effects of proinsulin C-peptide fragments on Na+, K+-ATPase activity
      of renal tubule segments.
AB  - Proinsulin C-peptide has been shown to stimulate the activity of Na+ K+ ATPase of
      rat renal tubule segments. Thirty-six peptides and amino acids, corresponding to
      parts of the intact rat C-peptide and suitable controls were screened for
      capacity to stimulate Na+, K+-ATPase in an attempt to determine potential active
      sites in the C-peptide molecule. The carboxy-terminal tetra and penta peptides
      were found to elicit 92-103% of the intact molecule's activity, and the remaining
      segment, des-(27-31) C-peptide, did not possess stimulatory activity. Peptides
      from the middle C-peptide segment, however, centering around a GGPEAG sequence,
      stimulated Na+, K+-ATPase activity (36-80% of the intact molecule's effect) but
      this effect was not balanced by corresponding inactivity of other parts.
      Furthermore, it was paralleled by activity of a non-native dipeptide D-form. It
      is concluded that the latter effect and that of the middle segment may represent
      complex interactions other than the apparently specific effects of the C-terminal
      segment.

PMID- 9541167
TI  - Repetitive mitochondrial Ca2+ signals synchronize with cytosolic Ca2+
      oscillations in the pancreatic beta-cell line, MIN6.
AB  - We examined the relationship between cytosolic Ca2+ concentration ([Ca2+]c) and
      mitochondrial matrix Ca2+ concentration ([Ca2+]m) in the pancreatic beta-cell
      line, MIN6. [Ca2+]c was monitored in a single or a group (30 cells) of fura-2
      loaded MIN6 cells, and [Ca2+]m was measured in a group (1 x 10[6] cells) of MIN6
      cells stably transfected with aequorin targeted at the mitochondria. Exogenous
      ATP (0.25 mmol/l) produced a single transient increase in [Ca2+]c whereas 22
      mmol/l KCl produced a sustained plateau increase. ATP and KCl evoked transient
      increases in [Ca2+]m but with distinct time courses of [Ca2+]m decline: the
      [Ca2+]m increase induced by ATP decreased more rapidly than that induced by KCl.
      Nitrendipine (3 micromol/l), a blocker of L-type Ca2+ channels, inhibited both
      [Ca2+]c and [Ca2+]m signals in response to KCl and tolbutamide, but not those to
      ATP. Peak levels of [Ca2+]m increase (around 2 micromol/ l) exceeded those of
      [Ca2+]c increase (around 500 nmol/l). A rise in glucose concentration from 3 to
      30 mmol/l induced oscillations of [Ca2+]c that overlay the sustained increases in
      [Ca2+]c in single cells. An oscillatory increase in [Ca2+]m was similarly
      observed in response to glucose. Addition of 10 mmol/l 2-ketoisocaproic acid at
      20 mmol/l glucose further increased the plateau level of [Ca2+]c and the
      frequency of [Ca2+]c oscillations, which were correlated with a further increase
      in [Ca2+]m. In response to pulsatile exposure to KCl, [Ca2+]c and [Ca2+]m
      increased synchronously. These data suggest that an oscillatory increase in
      [Ca2+]m in beta cells, the signal which is thought to be necessary for continuous
      stimulation of mitochondrial metabolism, is produced synchronously with the
      [Ca2+]c oscillations.

PMID- 9541169
TI  - The early phase of glucose-stimulated insulin secretion requires nitric oxide.
AB  - Nitric oxide (nitrogen monoxide, NO) acts as a signal transducer in a variety of
      cells. In the present study rat pancreatic islets were perifused with
      physiologically relevant glucose concentrations in the presence or absence of
      various NO-modulating agents. Perifusion in the presence of 0.1-1 mmol/l of the
      NO synthase inhibitor, NG-monomethyl-L-arginine or of 10 micromol/l of the NO
      scavenger, 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide
      (carboxy-PTIO), resulted in an inhibition of the early phase of glucose
      stimulated insulin secretion by 60-65% and 46%, respectively. Light- and electron
      microscopic studies revealed that pancreatic islets constitutively express NO
      synthase in alpha and delta cells, where it is confined to the secretory
      granules. Therefore, these data indicate that NO may be important in the signal
      transduction pathway of the early phase of glucose-stimulated insulin secretion.

PMID- 9541170
TI  - Target tissue production and axonal transport of neurotrophin-3 are reduced in
      streptozotocin-diabetic rats.
AB  - Neurotrophin-3 (NT-3) acts as a target-derived neurotrophic factor for large
      calibre sensory neurones and plays a role in the maintenance of the adult
      phenotype of proprioceptive and mechanoreceptive fibres. Large fibre sensory
      neuropathy is common in diabetes mellitus and the aim of this study was to
      determine whether endogenous NT-3-dependent neurotrophic support was sub-optimal
      in the streptozotocin-diabetic rat. NT-3 gene expression was analysed by Northern
      blotting and ELISA in hindlimb skeletal muscle and found to be decreased by up to
      70% (p < 0.05) in rats with 4-6 weeks of diabetes compared to aged-matched
      controls. Treatment of other diabetic rats with insulin prevented development of
      deficits of both NT-3 protein and of its mRNA. The deficits in target tissue
      production of NT-3 were coincident with significant decreases in its anterograde
      and retrograde axonal transport in sciatic nerve at 6 weeks of diabetes. The mRNA
      expression in lumbar dorsal root ganglia of the specific receptor for NT-3, trkC,
      was also down-regulated at 12 weeks of diabetes by 50% (p < 0.05). The observed
      decreases in NT-3 target tissue production and related axonal transport suggest
      that large calibre sensory neurones expressing trkC may be receiving sub-optimal
      neurotrophic support in experimental diabetes.

PMID- 9541171
TI  - Relative contribution of glycogenolysis and gluconeogenesis to hepatic glucose
      production in control and diabetic rats. A re-examination in the presence of
      euglycaemia.
AB  - Several studies have suggested that, in non-insulin-dependent diabetes mellitus,
      augmented gluconeogenesis is responsible for increased endogenous glucose
      production (EGP) and in the end determines fasting hyperglycaemia. However, human
      and animal studies have been conducted by comparing euglycaemic control subjects
      to hyperglycaemic diabetic probands. We measured EGP and hepatic gluconeogenesis
      comparing control and diabetic rats in the fasting state (with diabetic animals
      in hyperglycaemia), re-examining them in the presence of identical euglycaemia
      (with diabetic rats made acutely euglycaemic through i. v. phloridzin) or during
      a hyperinsulinaemic clamp. All rats were infused with [3-3H]-glucose and [U-14C]
      lactate; the ratio between 14C-uridine-diphosphoglucose (reflecting 14C-glucose 6
      phosphate) and 2 14C-phosphoenolpyruvate specific activities (both purified by
      high performance liquid chromatography from liver) measured hepatic
      gluconeogenesis. In diabetic animals, although overall EGP ( approximately 19.5
      mg x kg[-1] x min[-1]) remained unaffected by experimental euglycaemia, the
      contribution of glycogenolysis largely increased (from 5.4 to 11.7 mg x kg(-1)
      min(-1), hyper- vs euglycaemia) while gluconeogenesis decreased (from 14.0 to 8.1
      mg x kg(-1) x min[-1]); both were responsible for the augmented EGP (control
      rats, EGP: 12.7 mg x kg(-1) x min(-1); gluconeogenesis: 5.9 mg x kg(-1) x min(
      1); glycogenolysis: 6.7 mg x kg[-1] x min[-1]). Finally, during insulin clamp,
      gluconeogenesis and glycogenolysis were similarly decreased, and both contributed
      to the hepatic insulin-resistance of diabetic animals. We conclude that, in this
      model of non-insulin-dependent diabetes, augmented gluconeogenesis is not
      primarily responsible for fasting hyperglycaemia and hepatic insulin resistance.
      Finally, failure to accurately match the experimental conditions in which
      diabetic and control humans or animals are compared affects gluconeogenesis,
      overestimating its role in determining hyperglycaemia.

PMID- 9541172
TI  - Protection of islet allografts transplanted together with Fas ligand expressing
      testicular allografts.
AB  - Fas ligand (FasL) is highly expressed in testicular tissues and thought to be
      responsible for protection from allograft rejection by inducing apoptosis of anti
      graft activated T cells. FasL-expressing islets have been shown to induce a
      granulocyte-mediated inflammatory reaction. We investigated whether a graft can
      be protected from alloimmune responses by manipulating the Fas/FasL-system. We
      transplanted allogeneic islets under the kidney capsule of streptozotocin-induced
      diabetic mice together with testicular tissue. Significant prolongation of
      survival of C3H islet allograft was observed in C57BL/6 (B6) recipients
      transplanted with C3H testicular tissue, but not in those transplanted with C3H
      gld testicular tissue expressing non-functional FasL. No significant prolongation
      was observed in B6-lpr recipients expressing non-functional Fas.
      Immunohistochemical staining of C3H testicular tissue in the composite graft
      showed a high expression of FasL, but not that of the C3H-gld testicular tissue.
      In situ terminal deoxynucleotidyl transferase-mediated dUDP-biotin catalysed DNA
      nick-end labelling (TUNEL) staining of a composite graft of C3H islet and
      testicular tissue in B6 recipients demonstrated extensive apoptosis of
      infiltrating mononuclear cells around the graft. The protective effect of C3H
      testicular tissue was abrogated when anti-FasL monoclonal antibody was
      administered i.p. postoperatively. Our results suggest that FasL-positive
      testicular allografts protect composite islet allografts and indicate that
      manipulation of Fas/FasL mediated apoptosis is a suitable strategy for
      controlling rejection of islet allografts.

PMID- 9541173
TI  - Substitution of night-time continuous subcutaneous insulin infusion therapy for
      bedtime NPH insulin in a multiple injection regimen improves counterregulatory
      hormonal responses and warning symptoms of hypoglycaemia in IDDM.
AB  - In patients with insulin-dependent diabetes mellitus (IDDM) good glycaemic
      control confers an enhanced risk of hypoglycaemia. Nocturnal hypoglycaemia occurs
      frequently and contributes to the syndrome of hypoglycaemia unawareness. In order
      to avoid nocturnal hypoglycaemia we substituted night-time continuous
      subcutaneous insulin infusion (CSII) therapy in 14 patients with well-controlled
      IDDM using a multiple injection regimen for the more variable bedtime NPH
      insulin. During a stepwise hypoglycaemic clamp we studied the effect of this
      regimen on counterregulatory hormonal responses, warning symptoms and cognitive
      function. In addition, we investigated the incidence of daytime hypoglycaemia and
      the acceptability of night-time CSII treatment. CSII was associated with a lower
      frequency of hypoglycaemia (mean+/-SEM): 16.1+/-3.1 vs 23.6+/-3.3) episodes
      during the last 6 weeks of treatment, p=0.03 (CSII vs NPH)) with maintenance of
      good glycaemic control (HbA1c 7.2+/-0.2 vs 7.1+/-0.2 %, p=0.2). Hypoglycaemic
      thresholds for the growth hormone response and for autonomic symptoms were lower
      for CSII treatment than for NPH treatment. Of 14 patients 6 decided to continue
      with the nocturnal CSII treatment. In conclusion, nocturnal CSII improves warning
      symptoms and counterregulatory hormonal responses to hypoglycaemia and is an
      acceptable treatment strategy for patients suffering from hypoglycaemia
      unawareness, as demonstrated in this acute feasibility study.

PMID- 9541174
TI  - The potential role of cell adhesion molecules in the pathogenesis of diabetic
      neuropathy.
AB  - Cross-sectional studies have shown plasma cell adhesion molecules (CAMs) to be
      increased in patients with diabetes-related complications. In the first
      prospective study of CAMs, we have shown that plasma CAMs may be a predictor of
      the development of diabetic neuropathy. We followed up 28 diabetic patients (13
      neuropathic) over a 5 year period, starting from 1991. All patients had peroneal
      nerve conduction velocity (PNCV), vibration perception threshold and plasma CAMs
      measured at baseline and follow-up. We found P-selectin and intercellular
      adhesion molecule-1 (ICAM-1) to be increased at baseline in patients with
      neuropathy compared to non-neuropathic patients. P-selectin and E-selectin were
      also found to be significantly higher at baseline in patients who at follow-up
      showed deterioration in PNCV of more than 3 m/s (p<0.05; p=0.01; respectively). P
      selectin and ICAM-1 strongly correlated with PNCV. Univariate and multivariate
      regression analyses showed a significant inverse association between increasing
      log P-selectin, log E-selectin and log ICAM-1 with decreasing PNCV, and remained
      significant even after adjustment for glycaemic control. P-selectin and E
      selectin, odds ratios of 8.8 (95% CI: 1.1-68.8; p=0.038) and 12.5 (95% CI: 1.2
      132.1; p=0.036), respectively, were significantly associated with the risk of
      deterioration of PNCV after 5 years. This study suggests that plasma cell
      adhesion molecules may play an important role in the development and progression
      of peripheral neuropathy in diabetes mellitus.

PMID- 9541175
TI  - Abnormal regulation of cell membrane fluidity in diabetic nephropathy.
AB  - An abnormality of the physical properties of the cell membrane may underlie the
      defect that unites the clinical and biochemical abnormalities found in subjects
      with diabetic nephropathy. The cell membrane is linked both structurally and
      functionally with the cytoskeleton. The fluorescence anisotropy, a measure of
      membrane fluidity, was studied at baseline and after modulation of cytoskeletal
      proteins by thiol group alkylation with N-ethylmaleimide (NEM). 1,6-diphenyl
      1,3,5-hexatriene (DPH) was used to assess anisotropy in the deep hydrophobic
      regions of the lipid bilayer and trimethylammonium-diphenylhexatriene (TMA-DPH)
      was used to assess the superficial, relatively hydrophilic regions. We compared
      17 subjects with insulin-dependent diabetes mellitus (IDDM) and nephropathy with
      17 control subjects with IDDM and 24 non-diabetic control subjects. Median TMA
      DPH anisotropy (0.271 (0.239-0.332) vs 0.269 (0.258-0.281) vs 0.275 (0.246
      0.287)) and DPH anisotropy (0.221 (0.193-0.261) vs 0.227 (0.197-0.253) vs 0.226
      (0.193-0.245)) were similar in erythrocytes from the three groups. However after
      alkylation of protein thiol groups with NEM clear differences emerged. In the
      control subjects with and without IDDM there was a significant fall in TMA-DPH
      anisotropy compared to the subjects with diabetic nephropathy in whom the
      addition of NEM had no effect (deltaTMA-DPH anisotropy -0.005 (-0.020 - +0.006)
      vs -0.005 (-0.011 - +0.016) vs +0.002 (-0.010 - +0.008) p < 0.001). This finding
      was confirmed when the deep regions of the lipid bilayer were assessed using DPH
      (deltaDPH anisotropy -0.017 (-0.029 - -0.007.) vs -0.015 (-0.029 - +0.001) vs +
      0.003 (-0.021 - +0.018) p < 0.001). We conclude that cytoskeletal modulation of
      the physical properties of the cell membrane lipids by proteins is abnormal in
      subjects with diabetic nephropathy. Such an abnormality could explain some of the
      clinical and metabolic abnormalities found in this condition.

PMID- 9541176
TI  - Cytokine overproduction in healthy first degree relatives of patients with IDDM.
AB  - Healthy family members of patients with insulin-dependent diabetes mellitus
      (IDDM) are known to share a number of immunological abnormalities with their
      affected relatives. Since monocyte and type 1 T-cell-derived cytokines contribute
      to the pathogenesis of IDDM, we studied the production of these cytokines in the
      healthy first degree relatives of 29 children with IDDM. We report that
      circulating tumour necrosis factor-alpha (TNF-alpha) and soluble interleukin-2
      (sIL-2) receptor were present in increased amounts in non-diabetic family members
      at levels similar to those found in the diabetic children (duration of disease 3
      months-5 years). Furthermore, marked hypersecretion of IL-1alpha and TNF-alpha by
      mitogen-stimulated peripheral blood mononuclear cells was found in both diabetic
      and healthy family members. Abnormalities of cytokine production in healthy
      relatives did not correlate with the presence of islet cell antibodies or with
      HLA DR type. These data indicate that healthy family members of patients with
      IDDM exhibit overproduction of a number of cytokines that have been implicated in
      diabetogenesis.

PMID- 9541177
TI  - Autoantibodies to oxidised low density lipoproteins in IDDM are inversely related
      to metabolic control and microvascular complications.
AB  - Diabetes mellitus is associated with an increased risk of atherosclerosis. The
      oxidation of low-density lipoproteins (LDL) is considered a key event in the
      initiation of atherosclerosis. To investigate LDL oxidation in vivo we measured
      autoantibodies to oxidised LDL (oxLDL) in 94 patients with insulin-dependent
      diabetes mellitus (IDDM), compared to 27 age-matched, healthy control subjects.
      Patients and control subjects were screened for autoantibodies using a solid
      phase ELISA, comparing the binding to oxLDL with that to native LDL (nLDL). In
      patients with IDDM the oxLDL/nLDL antibody ratio was significantly higher than in
      control subjects (means+/-SEM: 2.24+/-0.26 vs 1.17+/-0.17, p < 0.03). Antibody
      negative patients had a longer diabetes duration (13.5+/-1.3 vs 9.1+/-1.1 years,
      p < 0.01) and higher actual and mean HbA1c levels compared to antibody-positive
      patients (8.8+/-0.2 vs 7.9+/-0.2%, p < 0.005 and 8.3+/-0.2 vs 7.7+/-0.2%, p <
      0.03; respectively). In patients with a high microangiopathy score, the antibody
      ratio was lower than in patients without complications (1.04+/-0.10 vs 2.40+/
      0.29, p < 0.01). OxLDL specific immune complexes were found exclusively in
      antibody-negative as compared to antibody-positive patients (18.3 vs 0 %; p <
      0.01). Our data demonstrate an inverse relationship between free oxLDL antibodies
      and the severity of the disease. This apparent paradox can be explained in part
      by our demonstration of oxLDL immune complexes, masking free antibodies.

PMID- 9541178
TI  - Synergistic effect of polymorphisms in uncoupling protein 1 and beta3-adrenergic
      receptor genes on basal metabolic rate in obese Finns.
AB  - The polymorphisms in the uncoupling protein 1 (UCP1, A to G) and beta3-adrenergic
      receptor (beta3-AR, Trp64Arg) genes have been suggested to be associated with an
      increased tendency to gain weight. We investigated the frequency of the A to G
      polymorphism of the UCP1 gene and its effect on basal metabolic rate (BMR) among
      obese Finns. We also examined the effects of the simultaneous occurrence of the
      polymorphisms in the UCP1 and beta3-AR genes on BMR. Altogether 170 obese
      subjects (29 men, 141 women, BMI 34.7beta3.8 kg/m2, age 43+/-8 years, mean+/-SD)
      participated in the study. The A to G substitution of the UCP1 gene was verified
      by digestion of the PCR product with Bcl I. The frequency of the A to G
      polymorphism of the UCP1 gene in obese subjects did not differ significantly from
      the population-based control subjects (5 vs 1 % for homozygotes (GG) and 35 vs 42
      % for heterozygotes (AG), p=0.077, for trend). BMR adjusted for lean body mass,
      age and sex (adjBMR) was similar among the three UCP1 gene genotypes of obese
      subjects (AA n=90, AG n=72 or GG n=8). However, the subjects with the
      polymorphisms in both UCP1 and beta3-AR genes (n=18) had a 79 kcal/day (95% CI 30
      128) lower adjBMR than the subjects without these polymorphisms (n=76) (1551+/-77
      vs 1629+/-141 kcal/day, p=0.002). Furthermore, adjBMR was 63 kcal/day (95 % CI 7
      118 kcal/day) lower in the subjects with both polymorphisms (n=18) compared with
      the subjects (n=14) who had only the polymorphism in the beta3-AR gene (1551+/-77
      vs 1613+/-76 kcal/day, p=0.028). The A to G polymorphism of the UCP1 gene did not
      have an independent effect on BMR, but its simultaneous existence with the
      Trp64Arg polymorphism of the beta3-AR gene resulted in more lowered BMR than the
      Trp64Arg polymorphism of beta3-AR gene alone.

PMID- 9541179
TI  - An aldose reductase inhibitor prevents glucose-induced increase in transforming
      growth factor-beta and protein kinase C activity in cultured mesangial cells.
AB  - We investigated the effect of inhibition of a polyol pathway on the glucose
      induced increase in transforming growth factor-beta (TGF-beta) production and
      activity of protein kinase C (PKC) in cultured human mesangial cells (MCs). The
      exposure of MCs to 33 mmol/l glucose resulted in an increase in TGFbeta
      production, measured by ELISA, compared with 5 mmol/l glucose. The glucose
      induced increase in TGF-beta was prevented by concomitant incubation with
      epalrestat, an aldose reductase inhibitor (ARI), in a dose-dependent manner at a
      concentration of more than 10(-6) mol/l. Moreover, the glucose-induced
      enhancement of PKC activity in the membrane fraction of MCs was also abolished by
      epalrestat. The addition of epalrestat to MCs cultured with 5 mmol/l glucose
      showed no demonstrable effects on TGF-beta production and PKC activity. These
      results provide direct evidence for linkages between derangements in polyol
      pathway and glucose-induced overproduction of TGF-beta and enhancement of PKC
      activity in MCs. Accordingly, the effect of an ARI on these metabolic
      abnormalities in MCs may justify its clinical application for treatment of
      diabetic nephropathy.

PMID- 9541180
TI  - Endothelial nitric oxide synthase gene polymorphism and coronary heart disease in
      Japanese NIDDM.

PMID- 9541181
TI  - Identification of genetic markers to 20 NIDDM candidate genes by radiation hybrid
      analysis.

PMID- 9541183
TI  - Report for the EASD-Bayer Travel Fellowship for Young Scientist 1997. European
      Association of the Study of Diabetes.

PMID- 9541182
TI  - Report about a three months' stay supported by the EASD-Bayer Travel Fellowship
      for Young Scientist 1997. European Association for the Study of Diabetes.

PMID- 9541184
TI  - The prognostic contribution of estrogen and progesterone receptor status to a
      modified version of the Nottingham Prognostic Index.
AB  - The aim of this study was to test the prognostic contribution of estrogen (ER)
      and progesterone (PgR) receptor status to an index consisting of the number of
      positive lymph nodes, the mean nuclear area of the breast cancer cells (MNA), and
      tumour diameter. This index is compared with a Danish index, which includes the
      same factors but uses histological grade instead of MNA. The Danish index has
      been developed from the Nottingham Prognostic Index (NPI). In the present study
      of 1629 breast cancer patients the Cox proportional hazard method is used to
      examine the time-dependency of the index, and to test for interaction between the
      index and the hormone receptors. The index sorts the patients into groups with
      low, intermediate, and high risk of dying. Logistic regression analysis is used
      to report the sensitivity and specificity of the index with and without ER and
      PgR. Our index gave information comparable to that of the Danish group. However,
      the information given by our index is time-dependent, its strength being weaker
      after 5-year of follow-up. PgR and ER add information to high risk patients, but
      only in the first 5-year period. High risk patients with positive hormone
      receptors have a prognosis similar to intermediate risk ones. PgR increases the
      ability of the index to predict breast cancer deaths correctly by 5 percent in
      high risk patients. In conclusion, PgR and ER act differently in groups of
      patients with different risk levels when time-dependency is considered. This
      indicates biological differences in subgroups as defined by the index.

PMID- 9541185
TI  - Changes in hormone receptors and proliferation markers in tamoxifen treated
      breast cancer patients and the relationship with response.
AB  - AIM: To determine the effects of tamoxifen on the levels of hormone receptors and
      proliferation markers in the early phase of treatment and the relationship of the
      changes with tumor response in patients with primary breast cancer. METHODS:
      Twenty-one women with primary, operable breast carcinomas were treated with
      tamoxifen 20 mg daily. Fine needle aspiration (FNA) was used to obtain samples
      prior to the start and at 14 days and 8-weeks post-treatment. From these samples
      estrogen receptor (ER), progesterone receptor (PgR), and Ki67 levels were
      determined using immunocytochemistry and ploidy and S-phase fraction (SPF) using
      flow cytometry. Tumor response was measured clinically according to UICC
      criteria. RESULTS: There were 12 responders (2 CR, 10 PR) and 9 non-responders (2
      NC, 7 PD). Responders were more likely to be ER+ (p = 0.002), PgR+ (p = 0.006),
      and low SPF (p = 0.06). At 14 days post-tamoxifen, the median decrease in Ki67 (%
      cells staining) for responders was -4.8 and for non-responders -0.15 (p = 0.005).
      This decrease was seen predominantly in ER+ tumours. The difference in SPF was
      not significant. A decrease in ER was seen in 3/15 patients all of whom were
      responders. A rise in PgR was seen in 7/17 patients and all but one were
      responders. Similar changes for ER and PgR were seen at 8-weeks post-tamoxifen,
      although the reductions in Ki67 and SPF at that time point were not related to
      response. CONCLUSION: We have observed a decrease in Ki67 and ER and a rise in
      PgR after 14 days of treatment with tamoxifen that was related to subsequent
      response. This is the first study in which an early decrease in a proliferation
      marker has been shown to relate to subsequent clinical response.

PMID- 9541187
TI  - Expression of a vitamin D-regulated gene (VDUP-1) in untreated- and MNU-treated
      rat mammary tissue.
AB  - Previous studies showed that the expression of an mRNA corresponding to VDUP-1
      was decreased within MNU-induced rat mammary tumors. RNA from mammary tissue was
      DNase treated and reverse transcribed and the resulting cDNA was amplified using
      primers designed to amplify VDUP-1 (382 bp fragment) and glyceraldehyde-6
      phosphate dehydrogenase (GAPDH) (416 bp fragment). Analysis of mammary cDNA
      derived from untreated or MNU-treated rats indicated that VDUP-1 expression
      within tumor tissue was significantly decreased, a finding which agrees with
      previous Northern blotting experiments. The differential expression was confirmed
      in tissue sections using an antisense VDUP-1 riboprobe for in situ hybridization
      studies which demonstrated that VDUP-1 staining in all cell types within tumor
      tissue was greatly decreased. VDUP-1 mRNA was expressed to a greater extent
      within epithelial cells and to a much lesser extent within stromal cells,
      including endothelial cells, in untreated mammary tissue. A significant decrease
      in VDUP-1 expression was detected as early as six weeks after MNU treatment,
      before tumors had formed. Bilateral ovariectomy did not alter VDUP-1 expression
      in untreated mammary tissue and ovariectomy prior to MNU treatment prevented
      tumor formation, as well as the associated decrease in VDUP-1 expression. The
      relative expression of VDUP-1 was higher in lung tissue than in adrenal, heart,
      kidney, liver, mammary, muscle, and ovary. Treatment of a cell line derived from
      an MNU-induced rat mammary tumor (MNU cells) with 1,25-dihydroxyvitamin D3
      resulted in a significant increase in VDUP-1 expression and also inhibited cell
      growth in the absence of serum. The data are consistent with a role for VDUP-1 in
      mediating the inhibitory effects of 1,25-dihydroxyvitamin D3 on tumor cell
      growth.

PMID- 9541186
TI  - A prospective study of the significance of gene and chromosome alterations as
      prognostic indicators of breast cancer patients with lymph node metastases.
AB  - In 150 surgically resected primary breast carcinomas that had axillary lymph-node
      metastases, we examined the incidence of loss of heterozygosity on chromosomes
      16p, 16q, 17p, 17q, and 18q, point mutation of the p53 tumor-suppressor gene,
      nuclear immunoreaction of p53 protein, and amplifications of the c-erbB-2 and int
      2 oncogenes by Southern blotting, single-strand conformation polymorphism
      analysis, and immunohistochemistry. We analyzed the association of these factors
      and conventional prognostic parameters with outcome of the patients, using Cox's
      univariate and multivariate analyses. The univariate analysis revealed that
      nuclear p53 immunoreaction, p53 mutation, and c-erbB-2 amplification as well as
      the number of metastatic lymph nodes, histological grade, and hormone-receptor
      statuses were significant prognostic indicators for both recurrence and cancer
      death. p53 immunoreaction was correlated more strongly with a poor prognosis than
      p53 mutations. The combination of p53 and c-erbB-2 effectively identified the
      high-risk patient group, and even among Grade 3 cases the subgroup with these
      alterations tended to have poorer clinical outcomes. The multivariate analysis
      including p53, c-erbB-2, and conventional factors. Lymph node status, grade, and
      p53 had independent impacts on the survival of patients. Under identical adjuvant
      systemic therapies, prognoses differed between the patient groups with and
      without alterations of p53 or c-erbB-2. Appropriate combinations of conventional
      factors with nuclear p53 immunoreaction and c-erbB-2 amplification would help to
      identify highly aggressive node-positive breast carcinomas and would aid
      stratification of patient groups in randomized clinical trials of adjuvant
      systemic therapies.

PMID- 9541189
TI  - Multidisciplinary weight management in locoregional breast cancer: results of a
      phase II study.
AB  - Sixty-one women with newly diagnosed locoregional breast cancer (T1-3, N0-1, M0)
      having an initial Body Mass Index (BMI) between 20 and 35 kg/m2 who were
      receiving standard adjuvant treatment (chemotherapy, tamoxifen, and/or radiation)
      were asked to avoid weight gain (if initial BMI < or = 25 kg/m2) or to lose up to
      10 kg (if initial BMI 25-35 kg/m2) over one year. Women participated in twenty
      group sessions (10 weekly, 10 monthly) which involved a psychological supportive
      expressive group intervention supplemented by individual weight goals, and
      nutrition and exercise programs. Fifty-five non-censored women (5 developed
      recurrence, 1 died of a subarachnoid hemorrhage) lost a mean of 0.53 +/- 3.72 kg.
      Weight loss was greatest in initially overweight women (BMI > or = 25 kg/m2) who
      lost 1.63 +/- 4.11 kg (p = 0.01 compared to normal weight women) and in those not
      receiving chemotherapy who lost 2.15 +/- 2.83 kg (p = 0.0004 compared to those
      receiving chemotherapy). 70.9% met predefined criteria for success. Aerobic
      exercise increased significantly during the intervention (p = 0.00005) and was
      the strongest predictor of success (OR 1.73 for each additional 30 minutes of
      exercise weekly, p = 0.003). Changes in caloric intake were not significant, but
      fat intake decreased and carbohydrate and fibre intake increased significantly
      during the intervention. Eating behavior and psychological status improved
      significantly. Thus, this multidisciplinary weight management intervention
      successfully prevented weight gain in women with newly diagnosed locoregional
      breast cancer, and helped overweight women lose weight.

PMID- 9541188
TI  - Effect of CGS 20267 on ovarian aromatase and gonadotropin levels in the rat.
AB  - Aromatase catalyzes the rate limiting step that converts androgens to estrogens.
      Postmenopausal women with hormone dependent breast cancer respond to first
      generation aromatase inhibitors such as aminoglutethimide with a marked
      suppression of circulating estradiol levels. In contrast, premenopausal women
      appear to be resistant to first generation aromatase inhibitors. The inability to
      block ovarian aromatase results from the low affinity of first generation
      inhibitors for the active site of the enzyme. Under these circumstances, the high
      substrate levels in the premenopausal ovary compete effectively with these
      inhibitors and do not allow binding of inhibitor to the active site of the
      enzyme. Second and third generation aromatase inhibitors with higher affinity for
      aromatase have now been developed and potentially could block ovarian aromatase.
      To test this possibility, we administered CGS 20267 (letrozole), a highly potent
      aromatase inhibitor, to cycling female rats. A dose dependent inhibition of
      uterine weight occurred with maximum effects produced by the 5 mg/kg/day dosage.
      During a period of 4 weeks, uterine weight was reduced to levels induced by
      ovariectomy. Ovarian tissue estradiol levels were inhibited by approximately 80%.
      As a reflection of inhibition of ovarian aromatase activity, the levels of
      androstenedione in the ovary increased by an order of magnitude. Both LH and FSH
      plasma levels increased but not to those observed after ovariectomy. The rise in
      gonadotropin levels induced a statistically significant but relatively small
      increase in ovarian weights. These results demonstrate the ability to
      persistently block ovarian aromatase activity in cycling rats with a potent
      aromatase inhibitor. This study provides a rationale for clinical trials of
      potent aromatase inhibitors in pre-menopausal women with breast cancer.

PMID- 9541190
TI  - An assessment of the influence of clinical breast examination reports on the
      interpretation of mammograms in a breast screening program. Ontario Breast
      Screening Program Radiologists Research Group.
AB  - The population-based Ontario Breast Screening Program (OBSP) provides two-yearly
      screening by both nurse examiner clinical breast examination (CBE) and two-view
      mammography to women aged 50 to 69. CBE alone accounts for about 5% of cancer
      detection. The purpose of this study was to determine whether CBE information
      affects radiologists' interpretation of mammography. Interpretation was defined
      by 1) radiologists' referral rates for diagnostic evaluation and 2) radiologists'
      accuracy in distinguishing cancer from non-cancer on mammograms. Mammograms were
      obtained from women randomly selected from those screened in the OBSP between
      1990 and 1992. Selection was stratified by whether or not the nurse examiner had
      independently referred for diagnostic evaluation. Additional women diagnosed with
      breast cancer were selected to increase the precision of the receiver-operating
      characteristic (ROC) curve. Each participating OBSP radiologist read a set of
      mammograms twice, approximately three weeks apart. The first reading was based on
      mammograms alone. At the second reading, the CBE report was included on the
      reporting form. Among 620 women referred by the nurse, radiologist referral rate
      increased from 37.7% to 40.8% (p = 0.079) when CBE information was available.
      Among the 637 not referred by the nurse, radiologist referral rate decreased from
      29.8% to 25.6% (p = 0.005). There was little effect on the sensitivity and
      specificity of radiologist referral and the areas under the two ROC curves (with
      and without CBE information) were not significantly different (p = 0.571).
      Although there was some effect of CBE information on radiologists' pattern of
      referral, there was no effect on accuracy of cancer detection.

PMID- 9541191
TI  - Prostate-specific antigen induction by a steroid hormone in T47D cells growing in
      SCID mice.
AB  - Previous studies revealed that prostate-specific antigen (PSA) is present in >
      30% of human breast tumor cytosols. Survival analysis showed that patients with
      PSA-producing tumors have a reduced risk for relapse, suggesting PSA to be an
      independent favorable prognostic marker for a large subset of breast cancer
      patients. The present investigation established an in vivo model for the
      induction of PSA in human breast cancer tumors growing as xenografts in severe
      combined immunodeficient (SCID) mice. The human mammary cancer cell-line T47D was
      grown i.m. in female mice. When the tumor and leg diameter reached 10 mm, the
      mice were stimulated daily with norgestrel for either 5 or 7 days to produce PSA,
      and sacrificed on day 8. The prostate cancer cell-line LNCaP was grown in male
      mice and functioned as a positive control for PSA production. After T47D and
      LNCaP mice were sacrificed, a highly sensitive immunofluorometric assay was used
      to analyze the PSA concentration in the tumor, muscle, liver, and kidney
      cytosols. Norgestrel-stimulated T47D mice showed significantly more PSA in the
      tumors compared to tumors of the control mice. However, PSA levels in tumors of
      the stimulated mice were significantly lower than those in the LNCaP xenografts.
      No PSA levels above background were present in the blood and normal tissue of the
      norgestrel-stimulated or control T47D xenografts. This mouse model will be a
      valuable tool for investigating and screening new therapies for a subgroup of
      breast cancer patients who have significant PSA concentrations in their tumors.

PMID- 9541192
TI  - Variation in endometrial thickening in women with amenorrhea on tamoxifen.
AB  - Tamoxifen is reported to increase the risk of endometrial cancers mostly in
      postmenopausal women. In the Royal Marsden chemoprevention programme, we noted
      that premenopausal women at the start of tamoxifen/placebo who developed
      amenorrhea may be at special risk of endometrial cancer. The aim of this report
      was to investigate recently amenorrheic women by measuring plasma estradiol (E2),
      follicular stimulating hormone (FSH), and endometrial thickness (ET) by
      transvaginal ultrasound (TVUS). ET readings and E2 levels were available in the
      same proportion of women on tamoxifen or placebo. Women on placebo developed
      amenorrhea with upper limit of E2 readings of 450 pmol/L. In both postmenopausal
      women and recently amenorrheic women with low E2 (< or = 450 pmol/L), tamoxifen
      significantly increased endometrial thickening (p < 0.0001 and < 0.005
      respectively). Conversely, tamoxifen did not result in endometrial thickening in
      women with high E2 (> 450 pmol/L), with a trend to lower ET readings (p = 0.07).
      Finally, all five women who developed endometrial cancer were premenopausal at
      the start of tamoxifen/placebo. Two of these five women were asymptomatic with
      increased ET readings (17 mm and 17 mm) and low E2 levels (32 and 51 pmol/L).
      These results indicate that women who develop amenorrhea on tamoxifen may be at
      special risk of endometrial cancer. Tamoxifen causes endometrial thickening in
      amenorrheic women with low E2 but has an opposite antiestrogenic effect in women
      with high E2. We recommend that women who develop amenorrhea on tamoxifen
      especially in the presence of endometrial thickening, low E2 levels, and/or
      gynaecological symptoms warrant further investigations.

PMID- 9541193
TI  - Predictive value of SRC-1 for tamoxifen response of recurrent breast cancer.
AB  - Tamoxifen causes an objective response in about one-third of metastatic breast
      cancer and in only half of the breast cancer patients with estrogen receptor (ER)
      positive tumors. Steroid-receptor coactivator-1 (SRC-1) appears to be a general
      coactivator for steroid receptors and rate limiting factor necessary for
      efficient ER transactivation. We aimed to evaluate whether SRC-1 expression is an
      additional factor for prediction of response to first-line tamoxifen therapy in
      patients who developed recurrent disease. Here for the first time, we report on
      SRC-1 expression using a semi-quantitative RT-PCR in 21 primary breast tumors,
      seven mammary tumor cell-lines, 12 fibroblast cultures, and six normal breast
      tissues. The highest levels of SRC-1 were observed in normal tissues,
      intermediate levels in tumor tissues, and the lowest levels in breast tumor cell
      lines. There was no relationship between the levels of SRC-1 in these primary
      tumors and the proportion of tumor cells within the surgical samples, nor with ER
      status. The median SRC-1 level was, however, lower in tumors from patients that
      did not respond to tamoxifen. Our findings suggest that high levels of SRC-1
      indicate a favorable response to tamoxifen of patients with recurrent breast
      cancer.

PMID- 9541194
TI  - Effect of menstrual phase on cell proliferative rate of breast cancer.

PMID- 9541195
TI  - Odontogenesis: a retrospective.

PMID- 9541196
TI  - A graphical WWW-database on gene expression in tooth.
AB  - We have constructed a WWW-site that presents gene expression in developing dental
      tissues (Gene expression in tooth, http://honeybee.helsinki.fi/toothexp). Our aim
      is to provide a tool for learning and for research, in particular to facilitate
      comparisons of the expression patterns of different genes and detection of their
      coexpression as a starting point for experimental studies. For this reason, we
      have included schematic illustrations of the gene expression in different stages
      of development when adequate information has been available. The site also
      contains a comprehensive list of references. Additionally phenotypic consequences
      of defective gene expression are indicated. The pages also provide links to other
      biological databases on the Internet, both as context-dependent and as general
      links. We welcome submissions from researches elsewhere to include their
      information of gene expression and function.

PMID- 9541197
TI  - Segmentation, crest prespecification and the control of facial form.
AB  - The early development of the vertebrate head is dependent on the formation of two
      series of segmented structures, the rhombomeres of the hindbrain and the
      branchial arch series. The initial formation of these two systems is closely
      linked, as the principal source of branchial arch mesenchyme is the neural crest,
      which derives from the lateral edge of the neural plate at the time of rhombomere
      formation. The subsequent development of the two systems maintains a close level
      of integration, as specific spatial relationships between skeletal, muscle and
      neural elements arising from the same axial level are established. Given the
      level of conservation of these anatomical relationships in vertebrates, it is
      likely that they are a reflection of a key mechanism in early facial and
      pharyngeal development. One model, in part based on these findings, proposed that
      the neural crest acquires an axial-level specific combination of gene expression
      while part of the neural plate. This prepattern is then maintained throughout the
      crest's subsequent development. In the model, this combination of gene expression
      would then specify the form of the facial and pharyngeal structures that the
      crest would give rise to. In this review we evaluate recent evidence on whether
      early facial development involves a crest prespecification of this type, and
      conclude that it is not the case.

PMID- 9541198
TI  - Contribution of foregut endoderm to tooth initiation of mandibular incisor in rat
      embryos.
AB  - Classical transplantation experiments with various amphibian tissues have shown
      that tooth development requires not only oral ectoderm and neural crest but also
      foregut endoderm. In addition, histological observation of oral membrane showed
      that the tooth germs are initiated in some ectodermal cells and neural crest
      cells adjacent to foregut endoderm. These studies suggest that tooth initiation
      requires the presence and cooperation of these three components. In mammals,
      however, there is no direct evidence that tooth formation is involved in the
      region of oral ectoderm adjacent to foregut endoderm. In order to elucidate the
      contribution of foregut endoderm to tooth formation, we established a new type of
      endodermal cell tracing system with a recombinant adenovirus called Adex-lacZ,
      and performed endodermal cell tracing in a long-term culture system. Cells
      labelled with Adex-lacZ were seen next to non-labelled thickening epithelium,
      presumptive incisor epithelium. These findings show the first direct evidence in
      mammals that tooth formation takes place in the specified part of oral ectoderm
      adjacent to foregut endoderm, suggesting that foregut endoderm plays a role in
      tooth initiation.

PMID- 9541199
TI  - Mesectoderm is a major target of retinoic acid action.
AB  - The RAR and RXR families of retinoid nuclear receptors each comprise three
      isotypes (alpha, beta and gamma). In vitro, RARs bind to their cognate DNA
      response elements as heterodimers with RXRs. Null mutations of all six isotypes
      have been generated. The defects displayed by RAR alpha, beta and gamma single
      null mutant mice are confined to a small subset of the tissues normally
      expressing these receptors. This discrepancy reflects the existence of a
      functional redundancy, since RAR double null mutants exhibit congenital
      malformations in almost every organ system. In particular, most of the structures
      derived from the mesectoderm are severely affected. Analysis of mutant mice
      lacking both RARs and RXRs indicates that RXR alpha:RAR gamma heterodimers are
      instrumental in the patterning of craniofacial skeletal elements, whereas RXR
      alpha:RAR alpha heterodimers may be preferentially involved in the generation of
      neural crest cell-derived arterial smooth muscle cells. Both RXR alpha:RAR beta
      and RXR alpha:RAR gamma heterodimers appear to function during the development of
      the ocular mesenchyme. Moreover, atavistic reptilian cranial structures are
      generated in RAR mutants, suggesting that the RA signal has been implicated in
      the modification of developmental programs in the mesectoderm during evolution.

PMID- 9541200
TI  - Parathyroid hormone-related protein is a developmental regulatory molecule.
AB  - Parathyroid hormone-related peptide (PTHrP) was discovered as the tumor product
      that is responsible for most instances of the syndrome of humoral hypercalcemia
      of malignancy. It is now known that the PTHrP and PTH genes arose on the basis of
      an ancient duplication event. One result of this heritage is a short stretch of
      highly homologous sequence at the N-terminus of each of the peptides, and another
      is the fact that these N-terminal products seem to be serviced by a single G
      protein-coupled receptor referred to as the type I receptor. Overexpression and
      null strategies in mice have recently provided convincing evidence that one such
      PTHrP function is as a developmental regulatory molecule. For example,
      overexpression of PTHrP in keratinocytes, mammary epithelial cells and
      chondrocytes results in a developmental phenotype in each case, while knockout of
      the gene is associated with a chondrodystrophy that is lethal at birth. Rescue of
      the PTHrP-null mouse via a genetic strategy involving a cross between the
      knockout mouse and a transgenic mouse with targeted PTHrP overexpression in
      chondrocytes provides a window on previously unappreciated PTHrP developmental
      regulatory effects in multiple tissues that share a common epithelial-mesenchymal
      morphogenetic background.

PMID- 9541201
TI  - Pax genes and organogenesis: Pax9 meets tooth development.
AB  - Pax genes encode a family of transcription factors that play key roles during
      embryogenesis. They are required for the development of a variety of organs
      including the nervous and muscular system, skeleton, eye, ear, kidney, thymus,
      and pancreas. Whereas the developmental roles of many of the nine known Pax genes
      have been analyzed in great detail, a functional analysis of Pax9 has just begun.
      During mouse embryogenesis, Pax9 exhibits a highly specific expression pattern in
      derivatives of the foregut endoderm, somites, limb mesenchyme, midbrain, and the
      cephalic neural crest. In the mandibular arch mesenchyme, the expression of Pax9
      marks the prospective sites of tooth development prior to any morphological signs
      of odontogenesis and is maintained in the developing tooth mesenchyme thereafter.
      To understand the function of Pax9 during mouse embryogenesis, we recently have
      created a null allele by gene targeting. Preliminary analyses show that Pax9 is
      essential for the formation of teeth, and we conclude that Pax9 is required for
      tooth development to proceed beyond the bud stage. Here, we briefly summarize our
      current knowledge about Pax genes and introduce Pax9 to the growing family of
      factors which are involved in tooth development.

PMID- 9541202
TI  - Molecular control of odontogenic patterning: positional dependent initiation and
      morphogenesis.
AB  - We have previously proposed that the patterning of the mammalian dentition is
      determined by an odontogenic homeobox code, whereby positional specification of
      odontogenic ectomesenchymal cell populations in a given region of the first
      branchial arch are determined by the combination of different homeobox genes
      expressed, described in detail in (1). Here we describe the first functional
      evidence for such a mechanism, and show that development of different types of
      teeth is controlled by independent genetic pathways. We suggest a mechanism
      whereby patterning is determined by position dependent control of tooth germ
      initiation, and propose that the pathway of morphogenesis is directly linked to
      the early mesenchymal expression of homeobox genes.

PMID- 9541203
TI  - Patterning of the murine dentition by homeobox genes.
AB  - Homeobox genes have been shown to be important for the regulation of pattern
      formation of many systems during embryogenesis. Overlapping domains of Hox gene
      expression in the paraxial mesoderm have been suggested to create a combinatorial
      code of expression (Hox code) specifying the structures of individual segments
      such as the vertebrae. Hox genes are not expressed in the neural crest cells
      contributing to tooth formation, and so a Hox code can not be involved in
      patterning the dentition. It has previously been proposed that other, non-Hox
      homeobox genes may pattern the dentition. Expression data in this paper shows
      that there is a pattern of overlapping domains of homeobox gene expression in
      facial mesenchyme prior to the initiation of tooth development. We propose that
      expression of these genes constitutes an odontogenic homeobox code which patterns
      the dentition.

PMID- 9541204
TI  - Perspectives on genetic aspects of dental patterning.
AB  - Nearly a century of speculation and experimentation has gone into trying to
      understand the mechanisms that establish the pattern of the differentiated
      heterodont dentition. Regionally differing qualitative (combinatorial) expression
      of regulatory genes appears to be involved in this process. Work by our
      laboratory and others shows that the six members of the mammalian Dlx family of
      homeobox genes are expressed (a) at multiple times during dental development, (b)
      differently at different stages, (c) in a way that is related to their genomic
      organization as gene-pairs linked to three of the four Hox clusters of positional
      patterning genes. The expression appears to be involved in jaw regionalization,
      tooth initiation, and tooth development. However, this expression correlates with
      no single aspect of dental patterning or tooth development, involves redundant
      and complementary function, and developmental differences between the maxillary
      and mandibular dentition suggest that other elements remain to be identified. For
      example, the possibility that quantitative aspects of gene expression specify
      developmental fields in the dentition has not yet been investigated. Although the
      maxilla and mandible develop differently, indirect evidence suggests that,
      especially in the future midline (incisor) regions, both jaws may be patterned by
      a consistent process that occurs before neural crest migration takes place, and
      we hypothesize that signaling factors like Sonic hedgehog and Pax transcription
      factors may be involved.

PMID- 9541206
TI  - Computer-aided graphical reconstructions of the development of murine dental
      primordia and surrounding structures from day 12 until birth.
AB  - There are studies that discuss spatial impediment as an important co-factor
      during tooth morphogenesis, especially to the cuspal folding pattern in relation
      to the space available for the primordium. The aim of this study is to give a
      description of the 3-dimensional aspect of the dental primordia of the NMRI mouse
      in relation to their surrounding hard tissue structures, and covering all
      prenatal stages from lamina to late bell. Serial histological sections were
      prepared from 31 specimens of NMRI mice from intrauterine days 12-19 (birth), and
      computer-aided 3D-reconstructions were made from light microscopic traces. During
      the early stages of days 12-15, the bony structures were too far away to exert a
      direct mechanical influence. However, from day 16 on (early bell stage in molar
      primordia), partial bony encapsulations with distances around 100 microm were
      found. Up to birth, when the folding pattern of the inner enamel epithelium
      became more prominent, a progressive bony encapsulation, with distances reduced
      to 40 microm, could be seen. Spatial impediment may be a possible co-factor in
      bell stages of dental morphogenesis.

PMID- 9541205
TI  - Early stages of tooth morphogenesis in mouse analyzed by 3D reconstructions.
AB  - Computer-aided 3D reconstructions were used to investigate early odontogenesis in
      the ICR mouse, from the dental lamina to the cap stage. The diastemal region of
      the maxilla was not an empty zone: five transient epithelial rudiments (D1-D5)
      were found between ED 12.5-13.5. Two further rudiments (R1 and R2) were observed
      between D5 and the maxillary first molar primordium, whose bud emerged at ED
      13.5. These rudiments might be related to vestiges of ancestral teeth. During
      this period, only an epithelial lamina was observed in front of the bud-shaped
      molar epithelium in the cheek region of the mandible. Apoptosis plays an
      important role in the reduction of antemolar rudiments in the maxilla and in the
      remodeling of the epithelium anterior to the M1 bud and cap in both jaws: two
      successive waves of apoptosis were detected in the mandible and in the maxilla.
      Computer-aided 3D reconstructions clearly demonstrated that morphologically
      different developmental stages coexist along the anteroposterior axis of M1 in
      both jaws.

PMID- 9541207
TI  - Neuronal cells and neurotrophins in odontogenesis.
AB  - There is evidence from lower animals that in addition to oral ectoderm and
      cranial neural crest, tooth formation depends on neuronal cells. To analyze the
      possible neural influence on mammalian tooth formation, peripheral nerve fibers
      and neuronal cells were localized in the area of the developing rat first molar
      tooth germ. Moreover, to study whether factors needed for neuronal development
      might be involved in the regulation of tooth formation and innervation,
      expression of NGF-related neurotrophic factors and their receptors were localized
      by in situ hybridization. The data suggest that although peripheral nerve fibers
      appear not to be required for odontogenesis, neuronal cells associated with the
      embryonic rat tooth may participate in the regulation of tooth formation.
      Localization of neurotrophins and their receptors suggests that besides their
      apparent roles in the regulation of tooth innervation, they may serve non
      neuronal, organogenetic functions during tooth formation. Moreover, it is
      possible that neuronal characteristics of the dental mesenchymal cells and the
      presence of neuronal cells in the tooth germs may explain the specific ability of
      neural crest-derived, but no other mesenchymal, cells to contribute to mammalian
      tooth formation.

PMID- 9541208
TI  - NGF, BDNF, NT3, NT4 and GDNF in tooth development.
AB  - Neurotrophic factors have robust effects on development, differentiation,
      maintenance and regeneration of neurons. In the present study, we have used in
      situ hybridization to determine the specific sites of gene activity of five
      neurotrophic factors during tooth development. Nerve growth factor (NGF) and
      brain-derived neurotrophic factor (BDNF) mRNAs were mainly detected in the dental
      papilla/pulp in postnatal rats, and the pattern of expression correlated with
      onset of dental innervation. In contrast, neurotrophin 3 (NT3) and 4 (NT4) mRNA
      expression patterns were predominantly epithelial and were strongest during early
      developmental stages when teeth are not yet innervated. Glial cell line-derived
      neurotrophic factor (GDNF) mRNA was present in dental epithelium at early stages,
      but later in development, GDNF mRNA expression was mainly mesenchymal and
      observed in the odontoblast layer and extending into the subodontoblast zone. Our
      results suggest that both neurotrophins and GDNF may have multiple functions
      during tooth development. In addition to an influence on the establishment of the
      dental innervation, neurotrophic substances might have morphogenetic effects such
      as modulating the proliferation or differentiation of developing epithelial and
      mesenchymal cells.

PMID- 9541209
TI  - EGF does not induce Msx-1 and Msx-2 in dental mesenchyme.
AB  - Previous heterospecific tissue recombinations indicate that mandibular epithelium
      exerts the first known inductive signal for odontogenesis in mouse embryos. BMP-4
      and EGF are two growth factors implicated as signaling molecules mediating the
      initial inductive epithelial-mesenchymal interactions during odontogenesis. The
      purpose of the present study was to examine and compare the effects of these
      growth factors and mouse mandibular epithelium on expression of Msx-1 and Msx-2
      genes in molar-forming mesenchyme. Agarose beads soaked in growth factors or
      pieces of mouse mandibular epithelium (E11) were placed in contact with E11 molar
      forming mesenchyme and cultured for 24 h. Whole-mount in situ hybridization
      analysis revealed that, in contrast to mouse mandibular epithelium and BMP-4
      releasing beads, EGF-releasing beads did not induce the expression of Msx-1 and
      Msx-2 in E11 molar-forming mesenchyme. These observations suggest that whereas
      BMP-4 may be involved in activation of Msx-1 and Msx-2 in the underlying
      mesenchyme, EGF may regulate events involved in the formation of dental lamina.

PMID- 9541210
TI  - Expression of p21(WAF1/CIP1) during mouse odontogenesis.
AB  - p21(WAF1/CIP1) is a cyclin-dependent kinase (Cdk) inhibitor. This protein may
      function during development as an inducible growth inhibitor that contributes to
      cell cycle exit and differentiation. The expression pattern of p21 during mouse
      embryogenesis was correlated with terminal differentiation of multiple cell
      lineages including skeletal muscles, cartilage, skin and nasal epithelium. p21
      expression was analyzed by in situ hybridization during odontogenesis as well as
      during in vitro tooth development in chemically defined medium with or without
      retinoic acid. p21 transcripts were detected in the restricted area of the inner
      dental epithelium during late cap and initial bell stages and then confined to
      the post-mitotic odontoblasts and ameloblasts. The replicating cells were devoid
      of any signal. The distribution of p21 mRNA in vitro, whatever the culture
      conditions, was similar to the in vivo pattern. p21 protein immunolocalization
      was superimposed on the transcripts distribution but more restricted in
      ameloblasts. TGFbeta1 is known to induce p21 expression. During dental
      cytodifferentiations, TGFbeta1 and p21 expressions overlap. Growth inhibition by
      TGFbeta1 may be associated with p21 induction.

PMID- 9541211
TI  - Expression of the transcription factors Otlx2, Barx1 and Sox9 during mouse
      odontogenesis.
AB  - The molecular mechanisms governing the decision between molariform and incisiform
      patterns of rodent dentition are not yet known. Transcription factors are
      regulators of regionally specific morphogenesis and key co-ordinators of gene
      activity during developmental processes. Here, we analysed the expression of
      several transcription factors during mouse tooth development. Otlx2/Rieg is a
      homeobox gene involved in Rieger syndrome, a human disorder characterized by
      dental hypoplasia. Otlx2/Rieg expression distinguishes stomatodeal epithelium
      well before tooth initiation, and thereafter its expression becomes restricted to
      the epithelia of both molar and incisor primordia. The recently identified
      homeodomain transcription factor Barx1 is first expressed in mesenchyme of the
      first branchial arch, but during advanced developmental stages the gene is
      exclusively expressed in the mesenchyme of molar primordia. Finally, the Sry
      related transcription factor Sox9 is expressed in epithelial components and to a
      lesser degree in condensed mesenchyme of the developing teeth. These results
      suggest that Otlx2/Rieg, Barx1, and Sox9 participate in the hierarchical cascade
      of factors involved in the regulation of tooth morphogenesis.

PMID- 9541212
TI  - Effects of aFGF, bFGF, TGFbeta1 and IGF-I on odontoblast differentiation in
      vitro.
AB  - In this work, we investigated the effects of aFGF and bFGF alone or combined with
      TGFbeta1 or IGF-I on odontoblast differentiation. Trypsin-isolated dental
      papillae from day 17 mandibular first molar were cultured in semisolid-agar
      medium for 6 d. Our results demonstrated that aFGF, bFGF or combinations of these
      promoted cell polarization at the periphery of the dental papillae. Moreover,
      simultaneous addition of aFGF and TGFbeta1 to dental papillae cultures induced
      both polarization and functional differentiation of odontoblast-like cells, as
      well as extracellular matrix deposition. Combination of aFGF or bFGF with IGF-I
      caused cell polarization at the surface of dental papillae, but matrix secretion
      was restricted to a few explants. In the presence of bFGF and TGFbeta1, the
      explants had pronounced cell elongations but no matrix deposition. These results
      indicate that aFGF or bFGF is not able to induce odontoblast differentiation
      alone. However, both aFGF and bFGF can act synergistically with TGFbeta1 and IGF
      I to strengthen their inductive effects and promote gradients of cytological and
      functional changes in odontoblast-like cells.

PMID- 9541214
TI  - Basement membrane-like structures occurring on the surface of dental papilla
      mesenchymal cells during odontogenesis in the monkey Macaca fuscata.
AB  - The aim of this study was to examine the nature of a basement membrane-like
      structure occurring along the surface of dental papilla cells during
      odontogenesis. The tooth germs of Japanese macaques (Macaca fuscata) were
      prepared for both ultrastructural and immunohistochemical studies. Characteristic
      discrete structures which resembled basement membranes were observed along the
      surface of the dental papilla cells, preodontoblasts, and also of the
      odontoblasts. Immunoperoxidase staining showed that these structures contained
      major basement membrane components including laminin, heparan sulfate
      proteoglycan, type IV collagen, as well as fibronectin. They tended to be less
      prominent along dental pulp fibroblasts and fully developed odontoblasts in
      comparison with those along the papilla cells localized close to the basement
      membrane of the inner enamel epithelium. Therefore, possible roles of these
      basement membrane-like structures would be: 1) to support the cells, 2) to
      momentarily secure the appropriate positions of differentiating mesenchymal
      cells, and 3) to regulate epithelial-mesenchymal interactions for odontoblast
      differentiation.

PMID- 9541213
TI  - A novel approach for inhibiting growth factor signalling in murine tooth
      development. Inhibition of FGF's.
AB  - Growth factors belonging to the FGF and TGF-beta families, together with other
      secreted factors such as Sonic hedgehog, have been shown to be spatially and
      temporally regulated during tooth development. Providing evidence of the
      functions of these molecules has, however, proved difficult. We have developed a
      novel strategy for investigating the role of secreted molecules in tooth
      development using soluble forms of membrane bound receptors to sequester ligands.
      Chimeric fusion proteins of receptor extracellular domains were cloned into the
      eukaryotic expression vector pIG-1 and transfected into COS cells. Fusion
      proteins secreted by the COS cells were purified using Protein A Sepharose. A
      soluble form of the FGF receptor FGF-1IIIc, which preferentially binds FGF-2 and
      FGF-4, was produced using this technique and added to mouse mandible cultures.
      Addition of the soluble receptors to E13 cultures resulted in down-regulation of
      Sonic hedgehog expression in molar enamel knots, consistent with inhibition of
      FGF-4 signalling.

PMID- 9541215
TI  - Freeze-fracture studies of the distal plasma membrane of rat odontoblasts during
      their differentiation and polarisation.
AB  - We have examined freeze-fracture replicas of maxillary first molar tooth germs of
      newborn rats at early stages of dentinogenesis to study the development of tight
      junctions in the distal plasma membrane of differentiating odontoblasts. In
      addition, freeze-fracture was combined with filipin to observe the distribution
      of cholesterol on the distal plasma membrane of odontoblasts during
      differentiation. Only gap junctions were present in early differentiating
      odontoblasts. The distal plasma membrane exhibited low cholesterol content, which
      might indicate high fluidity. With the beginning of mineral deposition in matrix
      vesicles, the first signs of tight junction formation were observed. Further
      development revealed increasingly complex focal tight junctions. In later stages,
      when mineralisation is observed progressing to the fibrillar and non-fibrillar
      constituents of the matrix, well developed focal tight junctions were detected.
      Concomitantly, cholesterol in distal portions of the odontoblast plasma membrane
      increased, indicating, probably, a higher rigidity. Thus, a distal plasma
      membrane domain is established, odontoblasts become fully differentiated, and
      partial compartmentalisation of matrix occurs. At this stage, odontoblasts may be
      able to secrete specific matrix molecules to ensure the progression of
      mineralisation.

PMID- 9541216
TI  - Dynamic expression of E-cadherin in ameloblasts and cementoblasts in mice.
AB  - During embryonic development, E-cadherin mediates intercellular adhesion in a
      variety of epithelia in a spatio-temporal pattern. We have analyzed the
      distribution of this cell adhesion molecule in the mouse during odontogenesis, at
      both mRNA and protein levels, in the mandibular first molars and incisors. E
      cadherin was strongly expressed at the bell stage by the cells of the dental
      organ, and by the pre-secretory ameloblasts and the cells of stratum intermedium
      at the early mineralization stage. At the onset of enamel secretion, E-cadherin
      disappeared from the apical pool of the ameloblasts and was later absent from the
      post-secretory ameloblasts. E-cadherin was also found in Hertwig's root sheath
      and later in the cells producing acellular cementum. These findings indicate that
      E-cadherin may be involved in the polarization of the ameloblasts and in the
      early stages of cementogenesis.

PMID- 9541217
TI  - Developmental role of PTHrP in murine molars.
AB  - Although PTHrP is produced in multiple fetal tissues, its precise physiological
      functions have yet to be clearly elucidated. The present study was undertaken to
      elucidate the biological role of PTHrP in the development of tooth. In rat tooth
      germs, the PTHrP and its receptor genes were expressed in the enamel organ and
      dental mesenchyme, respectively. When mouse tooth explants were cultured with
      antisense oligodeoxyribonucleotides (ODN) against mouse PTHrP mRNA in serum-free
      medium, an invasion of bone tissue was observed in the tooth germs. On the other
      hand, the explants cultured without ODN or with sense ODN showed normal
      histological structures similar to those observed in vivo. These results suggest
      that PTHrP is essential for tooth development and for the protection of tooth
      germs from the invasion of bone tissue.

PMID- 9541218
TI  - Immunolocalisation of collagens in the developing rat molar tooth.
AB  - This study identifies different types of collagens during tooth development,
      maturation and ageing. Tissues from the rat first molar (from animals ranging in
      age from E14 to 104 wk postnatally) were immunostained using a panel of mono- and
      polyclonal antibodies against types I, II, III, IV, VI, IX and X collagen,
      fibronectin and laminin. During tooth development, types I and III collagens were
      expressed in the dental papilla at all stages but were also unexpectedly observed
      in the stellate reticulum of the enamel organ. Transient expression of type II
      collagen was also observed in the stellate reticulum during the late bell stage.
      Types IV and VI collagens, with laminin and fibronectin, were located within the
      basement membranes of the tooth germ. Collagen types I and III were observed
      within the developing follicle/periodontal ligament, type III predominating where
      collagen fibres were inserting into the alveolar bone and cementum. The pattern
      of types I and III collagen labelling within the periodontal ligament and the
      dental pulp did not change with age. Thus, some unusual collagen localisations
      were observed in the tooth germ, particularly within the stellate reticulum.

PMID- 9541219
TI  - Effect of methotrexate on cell proliferation in developing hamster molar tooth
      germs in vitro.
AB  - Amongst the most frequently used drugs for the treatment of acute lymphoblastic
      leukaemia (ALL) belongs methotrexate (MTX), an inhibitor of pyrimidine
      (thymidine) synthesis. We examined effects of MTX on cell proliferation during
      tooth morphogenesis in organ culture by exposing hamster molar tooth germs to 10(
      7) to 10(-3) M MTX for 24 h. In the presence of serum, only the highest
      concentration of MTX (10(-3) M) induced a small, nonsignificant decrease in cell
      mass without histological changes but, unexpectedly, increased uptake of
      [3H]thymidine. In serumless conditions increase in cell mass (dry weight) and
      incorporation of [3H]thymidine was lower than in serum-supplemented conditions.
      Exposure to MTX in serumless conditions reduced the increase in cell mass even
      further without histological changes and, again, strongly enhanced incorporation
      of [3H]thymidine to the same proportion as measured in the serum-supplemented
      cultures exposed to MTX. The data suggest that only exposure to high levels of
      MTX reduces proliferation activity, shown by reduction in cell mass. The enhanced
      [3H]thymidine uptake under MTX exposure was explained by blockage of the internal
      biosynthesis of thymidine, by which action more radiolabel was taken up from the
      medium. The data also suggest that serum contains (growth) factors that stimulate
      cell proliferation, thereby increasing cell mass and [3H]thymidine incorporation.

PMID- 9541220
TI  - The bone morphogenetic protein family: multifunctional cellular regulators in the
      embryo and adult.
AB  - Originally identified as the active components within osteoinductive extracts
      derived from bone, the BMPs now are known to include a large family of proteins
      within the TGF-beta superfamily of growth and differentiation factors. Members of
      the BMP family have been determined to be key signaling molecules in
      embryogenesis, in species ranging from Drosophila to humans. They are involved in
      delivering positional information, the development of hard tissues (both bones
      and teeth), as well as soft tissue types. When implanted into adult animals,
      several of the BMPs have been shown to initiate the complex cellular process
      resulting in the induction of bone through both the endochondral and
      intramembranous bone formation pathways. Preclinical studies have shown the
      ability of these factors to induce bone and heal large bony defects in a variety
      of models relevant to clinical problems in orthopedics, as well as the oral and
      maxillofacial/dental areas. For example, implantation of recombinant human BMP-2
      (rhBMP-2) has been shown to augment the alveolar ridge in several animal models,
      and when placed in a periodontal environment to restore not only new bone, but
      also the attachment tissues. Results from ongoing clinical studies support the
      ability of rhBMP-2 implants to induce physiologic bone.

PMID- 9541221
TI  - Activin and bone morphogenetic protein (BMP) signalling during tooth development.
AB  - Activins and bone morphogenetic proteins (BMPs) belong to the transforming growth
      factor-beta (TGF-beta) superfamily of structurally related cytokines. Results of
      recent in vivo and in vitro studies suggest that activin A, several BMPs, and
      their cell surface receptors may participate in tooth development. In addition,
      follistatin an extracellular protein that may interact with activin and BMP
      signaling, appears to be involved. This review focuses on recent advances in
      relation to the roles of activin/BMP receptors, their ligands and extracellular
      modifiers during tooth development.

PMID- 9541222
TI  - RNAse protection assay for BMP type I receptors.
AB  - Bone morphogenetic proteins (BMPs) signal through a receptor complex comprising
      two distinct transmembrane serine/threonine kinases referred to as type I and
      type II receptors. The identification of at least three classes of type I
      receptors (ALK-2, -3, -6) and three classes of type II receptors for the BMPs,
      raises the possibility of multiple receptor complexes which may have distinct
      functions. An RNAse protection assay has been established which allows
      simultaneous analyses of the mRNAs for ALK-2, -3, and -6. As a test system,
      cultures of pluripotent C3H10T1/2 cell line were incubated in the presence or
      absence of BMP-7, and the relative levels of the receptor mRNAs were determined.
      Changes in receptor mRNA levels for ALK-2 and -3 were detected during the
      proliferation phase and adipogenic differentiation of the pluripotent C3H10T1/2
      cell line.

PMID- 9541223
TI  - Transforming growth factor-beta1 (TGF-beta1) in dentine matrix. Ligand activation
      and receptor expression.
AB  - Transforming Growth Factor-beta (TGF-beta) and other members of this family of
      growth factors have been implicated in tooth development and dental tissue
      repair. This study aimed to investigate regulatory factors for TGF-beta1 in
      rabbit incisor dentine matrix and the expression of receptors for TGF-beta in
      dental tissues better to understand the control of its biological activity.
      Approximately half of the TGF-beta1 in dentine matrix was present in active form.
      TGF-beta1 was found in association with latency associated peptide (LAP),
      betaglycan and decorin in an isolated dentine matrix preparation.
      Immunohistochemistry showed strong staining for TGF-beta type I and II receptors
      in odontoblasts with more variable and weaker staining of other pulpal cells.
      Association of TGF-beta1 with betaglycan, decorin and LAP may regulate the
      availability and biological activity of this growth factor and influence its
      presentation to the TGF-beta type I and II receptors on odontoblasts. During
      dental tissue repair, such control processes will be important in regulating the
      biological effects of TGF-beta1 on cells of the dentine-pulp complex.

PMID- 9541224
TI  - TGF-beta1 is essential for the homeostasis of the dentin-pulp complex.
AB  - Among the complex network of cytokines that influence odontoblast function during
      development and repair, TGF-beta1 is unique in its dual abilities to function as
      a potent immunosuppressant and as an inducer of extracellular matrix production.
      These properties underscore the importance of this molecule in maintaining the
      homeostasis of the dentin-pulp complex after injury. The purpose of this paper is
      to describe new findings of our phenotypic analysis of dentition in mice in which
      the TGF-beta1 gene has been disrupted. The major phenotype of TGF-beta1(-/-)
      offspring is one of diffuse immune system activation with progressive
      inflammation, wasting and death. Our studies of adult TGF-beta1(-/-) dentition
      show widespread pulpal and periapical inflammation and necroses. In addition, the
      coronal surfaces of occluding molars show marked attrition. To determine whether
      the phenotypic changes in TGF-beta1(-/-) dentition are directly linked to the
      loss of TGF-beta1 rather than the inflammatory process itself, we studied adult
      dentition in TGF-beta1(-/-) mice backcrossed into immunodeficient backgrounds.
      Results of our histopathologic and radiographic analyses show that teeth of TGF
      beta1(-/-) immunodeficient mice retain vitality in pulpal and periapical regions
      but show excessive wear of occlusal surfaces.

PMID- 9541225
TI  - Role of exogenous TGF-beta in induction of reparative dentinogenesis in vivo.
AB  - This study was designed to investigate in vivo i) the role of TGF-beta as an
      active component of the dentin matrix during induction of reparative
      dentinogenesis; and ii) the ability of TGF-beta1 isoform to induce dentinogenic
      events. Dental pulps of dog molars and canines were mechanically exposed, and the
      following implants were placed intrapulpally for 42 d: i) Demineralized or native
      autogenous dentin matrix preincubated with a TGF-beta-neutralizing antibody; ii)
      Millipore filters soaked with solution containing 100 ng/ml of TGF-beta1 from
      human platelets; iii) biomatrices and filters soaked in control solutions. After
      incubation of biomatrices with the TGF-beta-neutralizing antibody, demineralized
      dentin completely lost its inductive activity, while native dentin was only able
      to stimulate formation of fibrodentin. Millipore filters soaked with TGF-beta1
      were consistently surrounded by a thick zone of tubular matrix lined with high
      columnar polarized cells. The data provide evidence that pulp cells can express
      their dentinogenic potential in response to an appropriate surface containing
      exogenous TGF-beta1, and that the dentinogenic activity of dentin matrix may at
      least partly be ascribed to TGF-beta molecule(s).

PMID- 9541226
TI  - Regeneration of periodontal ligament and cementum by BMP-applied tissue
      engineering.
AB  - Previously, we demonstrated that the inductive properties of bone morphogenetic
      protein (BMP) highly depend on the nature of the carrier material used for
      implantation. In this paper, we show that administration of BMP incorporated in a
      fibrous collagen membrane can help to regenerate periodontal ligament and
      cementum both in cat canines and in monkey molars. The partially purified bovine
      BMP was combined with one or two layers of a fibrous collagen membrane. Although
      the single layer approach showed partial regeneration of periodontal defects, it
      also quite often led to ankylosis. The double layer technique in artificially
      prepared class III furcation defects in monkey molars gave favorable results.
      After 12 wk, not only the alveolar process but also the periodontal ligament and
      cementum had regenerated along the entire treated dentin surface. Collagen fibers
      were arranged more or less perpendicular to the surface of the new cementum.
      Ankylosis was not seen. It is concluded that the double-layer approach is
      superior to the single-layer technique in regenerating cementum.

PMID- 9541227
TI  - Dentin matrix proteins.
AB  - Dentinogenesis consists of highly controlled events occurring a short distance
      from the periphery of odontoblasts: it involves formation of extracellular
      collagen fibrils that act as an undergirding for deposition of plate-like
      carbonate apatite crystals. Odontoblasts also form a set of matrix proteins that
      are probably secreted at the mineralization front. Although most of these
      proteins are similar to those of bone, and differ from soft tissue proteins,
      dentin contains two unique proteins. Dentin phosphoprotein (DPP) is rich in
      aspartic acid (D) and phosphoserine (S*) and binds large amounts of calcium. DPP
      contains repeating sequences of DS*S* and S*D in discrete areas of the protein.
      DS*S* repeats form ridges of phosphates and carboxyllates while the S*D sequences
      give rise to ridges with phosphates and carboxyllates on opposing sides of the
      peptide chain. These structures undoubtedly have functional significance since
      DPP is involved in promotion of mineral initiation and in control of mineral size
      and shape. Dentin sialoprotein (DSP), found only in dentin, is a 53 kDa
      glycoprotein rich in aspartic acid, serine, glutamic acid and glycine. DSP is
      made by odontoblasts and also by pre-ameloblasts, but not by osteoblasts or other
      cell types. The gene for DSP is now known to be continuous with that of DPP.
      Thus, DSP and DPP must be secreted as a single protein which is then
      proteolytically processed to form the individual components found in the dentin
      matrix. Significantly, the DSP/DPP gene has been localized to human chromosome
      4q21 at a site implicated in dentinogenesis imperfecta type II.

PMID- 9541228
TI  - Six decades of dentinogenesis research. Historical and prospective views on
      phosphophoryn and dentin sialoprotein.
AB  - The molecular basis underlying the mineralization process associated with the
      conversion of predentin to dentin is poorly understood. What is clear is that a
      unique set of non-collagenous proteins (NCPs) participate in the nucleation
      process and in hydroxyapatite growth during dentin formation. Phosphophoryn (PP),
      the most abundant NCP in dentin, is secreted by odontoblasts and appears at the
      mineralization front. Dentin sialoprotein (DSP), another NCP, also appears at the
      mineralization front, but only accounts for 5-8% of the weight of dentin NCPs.
      Functionally, PP is believed to be directly involved in tile nucleation process
      by virtue of its ability to bind to collagen type I, and its high affinity for
      calcium ions. Based on the analysis of the putative rat PP amino acid sequence,
      this latter activity is believed due to the highly phosphorylated character of
      PP, which results from the dual actions of casein kinases I and II at selected
      domains within PP. The precise role of DSP is currently unknown. In situ studies
      demonstrate that DSP is substantially expressed in odontoblasts and transiently
      expressed in preameloblasts. However, no information is currently available to
      directly explain DSP's role in mineralization. Genetically, we and others have
      now identified a novel DSP-PP bicistronic mammalian transcriptional unit,
      suggesting that the functional roles of these two NCPs may also be tightly
      coupled with respect to dentinogenesis. Certainly, further exciting studies are
      now needed to explain how this DSP-PP transcriptional unit is finally expressed:
      whether DSP and PP associate with one another, or with collagen at the
      mineralization front: and how selective mutations in either gene may influence
      dentin mineralization.

PMID- 9541229
TI  - The phosphophoryn gene family: identical domain structures at the carboxyl end.
AB  - Phosphophoryns (PPs), a family of aspartic acid and phosphoserine rich dentin
      proteins, are considered to be archetypal regulators of extracellular matrix
      biomineralization. Their very unusual composition, extensive phosphorylation, and
      tissue-specific heterogeneity have made their characterization a difficult task.
      We have recently cloned several rat incisor PP genes from our odontoblast cDNA
      library. The first clone, designated as DMP2, was 2.4 kb long, with an open
      reading frame of approximately 700 bp and an untranslated region of approximately
      1.7 kb. Northern blot analysis of odontoblast mRNA showed a single message
      between 5 and 6 kb. When a 5' RACE technique was used to obtain the full length
      clone, a second approximately 2 kb DNA fragment (DMP3) was also found. Cloning
      and sequencing of DMP3 showed that the 3' end was highly homologous to the 3' end
      of DMP2, but the 5' end of this clone had 100% homology to dentin sialoprotein
      (DSP). DMP3 is not a typical Asp-rich phosphophoryn, but DMP2 contains a domain N
      terminal to the common region which has the hallmark Asp- and Ser-rich
      composition of the phosphophoryns. Both DMP2 and DMP3 are closely localized on
      mouse chromosome 5q21, corresponding to human chromosome 4q21. The expression of
      these two genes is regulated differently. Thus, there may be a family of
      phosphophoryn-related genes coding for a common C-terminal peptide sequence
      domain, but involving different N-terminal domains with different functions.

PMID- 9541230
TI  - Refined mapping of the human dentin sialophosphoprotein (DSPP) gene within the
      critical dentinogenesis imperfecta type II and dentin dysplasia type II loci.
AB  - Dentinogenesis imperfecta type II and dentin dysplasia type II are diseases
      resulting in abnormal dentin formation, which have been mapped to overlapping
      regions of human chromosome 4q defined by markers D4S2691 and D4S2692 (6.6 cM)
      and D4S3291 and SPP1 (14.1 cM), respectively. Recently, two of the major non
      collagenous proteins of dentin, dentin sialoprotein (DSP) and dentin
      phosphoprotein (DPP, phosphophoryn) have been shown to be encoded by a single
      gene, termed dentin sialophosphoprotein (DSPP), which has been mapped to human
      chromosome 4. The purpose of this study was to perform refined mapping of DSPP
      related to these disease loci by gene content mapping, as well as to place the
      DSPP gene on the physical map of human chromosome 4 by sequence tagged site (STS)
      content mapping. Human genomic DSPP clones were isolated, and gene content
      mapping performed with specific primers for dentin matrix protein 1 (DMP1), bone
      sialoprotein (BSP) and osteopontin (secreted phosphoprotein 1, SPP1). STS content
      mapping was then performed with flanking STS markers to these dentin/bone gene
      loci. Our results demonstrate that the DSPP and DMP1 genes are within a maximum
      distance of 110 kb. Both DSPP and DMP-1 have been placed on the physical map of
      human chromosome 4 within the interval defined by markers D4S564 and D4S1292.
      DSPP is thereby strengthened as a candidate gene for both DGI-II and DD-II.

PMID- 9541232
TI  - Dentin phosphoprotein sequence motifs and molecular modeling: conformational
      adaptations to mineral crystals.
AB  - Molecular modeling has been used to investigate structural features of
      oligopeptides derived from possible primary structure motifs in highly
      phosphorylated dentin phosphoprotein (PP-H), the predominant noncollagenous
      protein in dentin. It contains a large number of aspartate (Asp) and
      phosphoserine (Pse) residues, the latter proposedly crucial for the PP-H function
      as a mineral nucleator. In this work, computer fitting and subsequent structural
      adaptation of model peptides, built exclusively from Asp and Pse, to the known
      crystal structures of hydroxyapatite (HAP) and octacalcium phosphate (OCP) were
      performed. The results show that, when considering conformational energies of
      fitted single strand oligo-peptides, either crystal will serve. Within a narrow
      range, fitting to OCP was slightly favored, except for oligo(Pse-Pse-Asp-Asp),
      which showed a slightly better fit to HAP. Energy differences between crystal
      adapted and non-adapted freely minimized peptides showed that oligo(Pse-Asp)
      docked to either HAP or OCP were the energetically most favored adaptations.
      Fitting of minimized triple anti-parallel beta-strands of oligo(Pse-Asp) or
      oligo(Pse-Pse-Asp), motifs found in published sequences of rat, mouse, and bovine
      PP-H, revealed that a (001) crystal face of HAP, but most likely not OCP, may be
      formed by these beta-sheet models. The former motif is more advantageous in this
      respect.

PMID- 9541231
TI  - Properties of the (DSS)n triplet repeat domain of rat dentin phosphophoryn.
AB  - Phosphophoryns (PPs) are unique aspartic acid and phosphoserine-rich proteins
      present in all species of dentin. Rat incisor odontoblast cDNA libraries contain
      messages encoding several acidic phosphorylated, serine-rich proteins. At least
      two of these share a common C-terminal domain coding region sequence. The
      polypeptide sequences in the N-terminal direction immediately adjacent to the
      conserved C-terminal domains of these two proteins (DMP2, DMP3) are distinctly
      different. In this domain, the DMP2 has extensive sequences of (DSS)n repeats
      with n as large as 24. DMP3 has fewer and shorter triplet sequences, n = 3, 4.
      The major rat incisor PPs (90-95 kDa) probably have the (DSS)n>>3. We propose
      that the name phosphophoryn be reserved for the extracellular matrix proteins
      with these extended repeats. DMPI, although strongly acidic, does not fit this
      category. If the S residues are phosphorylated and n > 3, conformational energy
      minimization computations show the (DSS)n sequence to assume a unique extended
      structure with parallel arrays of carboxylate and phosphate groups which may
      function as Ca2+ ion interaction edges. The phosphorylation of recombinant DMP2 C
      terminal domain by various kinases has been examined. The repeat domains are not
      direct substrates for the CK2-like kinases but the kinases act in concert, so
      that the phosphorylation is hierarchical, apparently controlled by the presence
      of specific interruptions between the triplet domains.

PMID- 9541233
TI  - Conformation of dentin phosphophoryn adsorbed on hydroxyapatite crystals.
AB  - Phosphophoryn, the major noncollagenous protein of dentin, was adsorbed on
      synthetic hydroxyapatite crystals and analyzed by high-resolution solid-state
      nuclear magnetic resonance (NMR) spectroscopy. Binding of the protein was
      inhibited by acidic polypeptides, especially by a phosphorylated peptide. After
      phosphophoryn was incubated with the crystals, the crystals were collected and
      analyzed by 13C-cross-polarization magic-angle-spinning NMR. Several signals
      could be assigned to carbons of aspartic acids, taking advantage of the unique
      amino acid composition of this protein. Chemical shifts of signals of aspartic
      acids are known to reflect secondary structure of the polypeptide. The chemical
      shifts obtained from the phosphophoryn indicate that the secondary structure of
      this protein on the crystal was near to a beta-sheet structure. This result is
      consistent with the result for poly(Asp) adsorbed on the crystals. The beta-sheet
      like structure enables phosphophoryn to extend on the crystal surface and to
      cover the surface with only a small number of the molecules, resulting in the
      high inhibitory effect of this protein on crystal growth.

PMID- 9541234
TI  - Comparative analysis of mouse DSP and DPP expression in odontoblasts,
      preameloblasts, and experimentally induced odontoblast-like cells.
AB  - Dentin sialoprotein (DSP) and dentin phosphoproteins (DPP) are uniquely expressed
      by differentiating and fully differentiated mature odontoblasts. It is likely
      that DSP and DPP actively participate in the conversion of predentin to dentin.
      To compare the expression patterns of DPP and DSP, we constructed mouse cDNA
      probes. Northern analyses confirmed their specific expressions in tooth germ
      derived RNA and showed that the probes reacted with similar or identical multiple
      transcripts. In situ hybridization indicated that DSP and DPP transcripts were
      uniquely detected and codistributed in developing mouse odontoblasts and
      preameloblasts. These data, as well as the adjacent positioning of the DSP and
      DPP coding sequences, suggest that common regulatory mechanisms control DSP and
      DPP expressions. Dental papillae cultures, in which odontoblast differentiation
      was experimentally induced with TGFbeta1 combined with heparin, were used to show
      that the two molecules are also coexpressed under in vitro conditions.

PMID- 9541235
TI  - Dentin-specific proteins in MDPC-23 cell line.
AB  - Only four established odontoblast-like cell lines have been reported in the
      literature (1-6). Of the four, only two synthesize dentin-specific proteins.
      These studies report that the cell line MO6-G3 synthesizes phosphophoryn (DPP),
      dentin sialoprotein (DSP) and dentin matrix protein-1 (DMP-1) while MDPC-23
      synthesizes DSP, but not DMP-1. The objective of the present study was to
      determine whether polyclonal antibodies to rat DSP and DPP would label
      odontoblasts on microscopic sections of day-19 fetal mouse incisor odontoblasts
      as well as cultured cells of the MDPC-23 cell line. The spontaneously
      immortalized MDPC-23 cell line was derived from fetal mouse molar papillae, made
      continuous by the 3T6 method and cloned by dilution. These cultures have been
      passaged 77 times after cloning, form multilayered nodules, and have high
      alkaline phosphatase activity. The data show positive reactivity in odontoblasts
      in 19-d mouse fetal incisors as well as in cultures of MDPC-23 cells by
      fluorescence and confocal microscopy. In addition, these cultures were
      characterized by phase microscopy and scanning and transmission electron
      microscopy. These findings suggest that MDPC-23 cells are of the odontoblast
      lineage.

PMID- 9541236
TI  - Calcium- and hydroxyapatite-binding properties of glucuronic acid-rich and
      iduronic acid-rich glycosaminoglycans and proteoglycans.
AB  - This study describes the interaction of a small chondroitin sulphate proteoglycan
      and the glycosaminoglycans chondroitin 4-sulphate, dermatan sulphate and heparan
      sulphate with hydroxyapatite. All macromolecules possessed a high affinity, with
      the iduronic acid-rich dermatan sulphate and heparan sulphate displaying higher
      adsorption maxima than the glucuronic acid-rich chondroitin 4-sulphate. At
      similar concentrations, dermatan sulphate produced a 30% inhibition of
      hydroxyapatite-induced crystal growth, whilst chondroitin 4-sulphate yielded 50%
      inhibition. Estimation of the calcium binding capacity of these
      glycosaminoglycans using equilibrium dialysis indicated that chondroitin 4
      sulphate bound five times more calcium than dermatan sulphate at a calcium
      concentration similar to that of serum. The data indicate a possible important
      role for chondroitin 4-sulphate in dentinogenesis where it is the dominant
      glycosaminoglycan, since it could act as a capture point for calcium ions during
      mineralisation, with the leucine-rich domain of its parent proteoglycan acting as
      anchor points to type I collagen.

PMID- 9541237
TI  - Demonstration of putative Ca-binding domains in dentin matrix of rat incisors
      after daily injections of 1-hydroxyethylidene-1,1-bisphosphonate (HEBP).
AB  - In order to clarify the initial process of dentin mineralization, the inhibitory
      effect of 1-hydroxyethylidene-1,1-bisphosphonate (HEBP) on dentin mineralization
      was investigated. Rats (100 g) were subcutaneously injected with HEBP (8 mg P/kg)
      for 7 or 14 d, and the incisors were processed for Ca histochemistry and/or
      electron microscopy. HEBP-treated incisors demonstrated ladder-like alternate
      rows of mineralized and non-mineralized dentin at the apical end. GBHA revealed
      moderate Ca reactions in the non-mineralized circumpulpal dentin matrix where
      electron microscopy revealed rich distribution of fine mesh-like electron-dense
      material. Non-mineralized mantle dentin matrix was negative for Ca but contained
      numerous matrix vesicles (MVs) filled with crystalline and/or amorphous mineral
      deposits. Mineralization of circumpulpal dentin occurred independently of MV-rich
      mantle dentin layer in affected specimens. Our data provide histochemical
      evidence of possible Ca-binding property of the circumpulpal dentin matrix and
      its absence in the mantle dentin where MV-mediated mineralization occurs. In the
      mantle dentin, HEBP does not interfere with crystal growth in MVs but inhibits
      its outgrowth after membrane rupture. It is proposed that circumpulpal dentin
      matrix has a potential to mineralize independently of MV-mediated mineralization
      of mantle dentin, although MVs determine the initial site and timing of dentin
      mineralization.

PMID- 9541238
TI  - The developing enamel matrix: nature and function.
AB  - The hydroxyapatite crystals of mature enamel are unusually large, uniform and
      regularly disposed within the tissue, implying that their development is a highly
      controlled process. The organic matrix of developing enamel is presumed to play
      an important role in the modulation of mineral deposition and growth during tooth
      morphogenesis but the precise functions of individual matrix proteins remain
      unclear. The aim of this review was to survey the current knowledge of enamel
      matrix proteins with a view to suggesting possible functions. The organic matrix
      is highly heterogeneous, comprising proteins derived from a number of different
      genes, including amelogenin, enamelin, ameloblastin (amelin/sheathlin), tuftelin,
      dentine sialophosphoprotein, enzymes and serum proteins such as albumin. Each of
      these classes appears to undergo post-secretory sequential degradation which
      contributes further towards matrix heterogeneity. Possible functions of these
      proteins include de novo mineral nucleation/initiation (dentine
      sialophosphoprotein, tuftelin), mineral ion binding as crystal precursors
      (amelogenin, enamelin), control of crystal growth (amelogenin, enamelin,
      ameloblastin), support of growing crystals (amelogenin, enamelin), determination
      of prismatic structure (ameloblastin), cell signalling (tuftelin, ameloblastin),
      control of secretion (breakdown products) and protection of the mineral phase
      (amelogenin, enamelin). Failure of these mechanisms could lead to incomplete
      maturation of the enamel and the eruption of dysplastic tissue.

PMID- 9541239
TI  - DNA sequences of amelogenin genes provide clues to regulation of expression.
AB  - The amelogenins are a heterogeneous group of enamel proteins, which have an
      important function in enamel formation, as mutations in the amelogenin gene
      result in the enamel defect amelogenesis imperfecta. The cDNAs that encode
      murine, bovine, human, porcine, rat and opossum amelogenins have been cloned, and
      as many as nine alternatively spliced messages can be produced from a single
      primary transcript, explaining some of the protein heterogeneity. Bovine and
      human amelogenin genes are found on both X and Y chromosomes, and the sexually
      dimorphic proteins would have 87-93% identity. A comparison of genes from human,
      bovine and mouse indicates that they are organized into seven exons, and
      sequences are highly homologous among species. Bovine, murine and human upstream
      regions also have similarities, with consensus sequences for potential binding of
      transcription factors, such as AP1 and CTF/NF1. Transgenic mouse studies have
      shown that 2300-3500 bp of upstream region are sufficient for expression, while
      900 bp are insufficient. Analysis of DNA sequence has identified (a) major
      homology between species for coding exons with the exception of exon 4, (b)
      similarities in upstream regions likely involved in tissue specific regulation of
      expression, and (c) sequences at the RNA splice sites which may determine exon
      inclusion or skipping.

PMID- 9541241
TI  - Sheath proteins: synthesis, secretion, degradation and fate in forming enamel.
AB  - We investigated expression of ameloblastin and sheathlin, recently cloned enamel
      matrix proteins from the rat and pig, in forming enamel immunocytochemically and
      immunochemically, using region-specific antibodies. The results obtained from the
      rat and pig were essentially the same. Antibodies which recognize the N-terminal
      region stained the secretory machinery of the secretory ameloblast and the entire
      thickness of the enamel matrix, especially the peripheral region of the enamel
      rod. Immunostained protein bands were observed near 65 or 70 kDa and below 20
      kDa. C-terminal-specific antibodies stained the secretory machinery of the
      ameloblast and the immature enamel adjacent to the secretion sites. Immunostained
      protein bands were found ranging from 25 to 70 kDa. Antibodies which recognize a
      region in the protein just prior to the C-terminal region stained the cis-side of
      the Golgi apparatus but not the enamel matrix. Immunostained protein bands were
      observed of about 55 kDa. These results suggest that post-translational and post
      secretory modifications of ameloblastin and sheathlin are similar to each other,
      and further showed that their cleaved N-terminal polypeptides concentrate in the
      prism sheath. We propose that sheathlin and ameloblastin share the same role in
      amelogenesis and should be classified as sheath proteins.

PMID- 9541240
TI  - Derived protein and cDNA sequences of hamster amelogenin.
AB  - Hamster enamel protein extracts were analyzed by RP-HPLC and the isolated
      fractions by SDS-and Western blotting using polyclonal antibodies against
      recombinant mouse amelogenin and anti-peptide antibodies against the mouse exon 4
      encoded sequence. Total RNA was extracted from enamel organ epithelia and, using
      a 3' rapid amplification of cDNA ends (3' RACE) technique, the coding regions for
      three different amelogenin isoforms were cloned along with the 3' non-coding
      region. DNA sequencing revealed that the hamster amelogenin isoforms are 180, 73
      and 59 amino acids in length, respectively. The 59-residue amelogenin corresponds
      to the leucine-rich amelogenin protein (LRAP), the 73-residue amelogenin
      corresponds to LRAP with the inclusion of the exon 4-encoded sequence, while the
      180-residue amelogenin is the most abundant amelogenin isoform. Edman degradation
      was performed on purified hamster amelogenin, which provided the amino acid
      sequence in the region encoded by the 5' PCR amplification primer used in
      cloning. Therefore, the entire derived amino acid sequence of hamster amelogenin
      was revealed. The hamster amelogenin amino acid sequence was aligned with all its
      known homologues. Hamster differs from rat and mouse amelogenin at only three
      amino acid positions. Southern blot analysis using a panel of restriction enzymes
      gave the same pattern for hamster DNA obtained from males and females, suggesting
      that in hamster, as in mouse, amelogenin is expressed from a single gene located
      on the X chromosome.

PMID- 9541242
TI  - Tuftelin--aspects of protein and gene structure.
AB  - The acidic enamel protein tuftelin has now been cDNA cloned, sequenced and
      characterized in a number of vertebrate species. Recently, the bovine tuftelin
      gene structure was elucidated. Cloning of the human tuftelin gene and partial
      sequencing of a number of exons have also been achieved. Immunologically, the
      protein has been shown to be conserved throughout 550 million years of vertebrate
      evolution. The gene has been localized to the long arm of the autosomal
      chromosome 1. The mapping of the human tuftelin gene to a well-defined
      cytogenetic region could be important in understanding the etiology of
      autosomally inherited amelogenesis imperfecta, the most common hereditary disease
      of enamel. The present paper reviews the primary structure, mRNA/cDNA structure,
      and gene structure of tuftelin. It describes its immunolocalization at the light
      microscope level and at the ultrastructural level in both the ameloblast cells
      and in the extracellular enamel matrix. The timing of tuftelin expression and its
      possible roles in enamel formation are discussed.

PMID- 9541243
TI  - Sequential expression of an amelin gene in mesenchymal and epithelial cells
      during odontogenesis in rats.
AB  - Novel mRNA isoforms encoding the enamel matrix proteins amelin-1, amelin-2 and
      ameloblastin have been recently described. We have applied detailed
      immunohistochemical as well as non-radioactive in situ hybridization analyses to
      follow amelin-1 expression in developing rat incisors and molars. We constructed
      an expression vector, overproduced recombinant amelin in Escherichia coli and
      prepared an antibody. In addition to the previously reported amelin mRNA
      expression patterns in ameloblasts, the amelin message was also detected in
      pulpal mesenchymal cells including preodontoblasts and young odontoblasts. The
      signal in these cells persisted until deposition of mantle dentin became evident.
      The immunolocalization of amelin-1 in preodontoblasts and ameloblasts essentially
      followed the pattern of mRNA expression. The most intense staining was found in
      the enamel matrix adjacent to secretory ameloblasts. Focal accumulations of
      immunoreactive material were found at the dentinoenamel junction during the
      maturation stage. Also, using 5'-RACE (Rapid Amplification of cDNA Ends) we could
      confirm only amelin-1 and ameloblastin messages in the total RNA pool from rat
      molars and conclude that amelin-2 is a truncated form of ameloblastin. The
      sequential expression of amelin in mesenchymal and epithelial cells suggests it
      plays a role in cell differentiation during early tooth development.

PMID- 9541244
TI  - Enamel epithelium expresses bone sialoprotein (BSP).
AB  - Bone sialoprotein (BSP) is a major non-collagenous extracellular matrix protein
      in bone and other mineralized connective tissues. BSP is synthesized and secreted
      by bone-, dentin- and cementum-forming cells. In this study we hypothesized that
      BSP may be also involved in enamel formation through its postulated role in
      matrix mineralization. In situ hybridization with cRNA probes for rat and hamster
      BSP, respectively, showed strong mRNA signals in ameloblasts actively
      synthesizing enamel matrix in developing incisors. However, no hybridization
      signals were observed at an earlier developmental stage when bell-shaped molar
      tooth germs were being formed. Immunohistochemical analysis of tooth tissues from
      transgenic mice harboring a 2.7 kb rat BSP promoter ligated to a luciferase
      reporter gene revealed strong staining for luciferase in the enamel epithelium of
      the developing tooth germ. Interestingly, BSP expression was also observed in
      epithelial cells of an ameloblastoma. The neoplastic epithelial nests and cords
      demonstrated strong mRNA signals to the human BSP probe while the connective
      tissue stroma showed only a background level of silver grains. Immunostaining
      also showed deposition of BSP by the odontogenic cells of the tumor. These
      results demonstrate that BSP is expressed by the enamel-forming epithelium of
      developing teeth, suggesting a possible role for BSP in enamel formation and its
      subsequent mineralization. Expression of the BSP gene in ameloblastomas is
      consistent with the expression of BSP by the enamel epithelium and also with the
      expression of BSP by neoplastic tissues, suggesting a possible role in
      tumorigenesis.

PMID- 9541245
TI  - Proteolytic activity of opossum tooth extracts.
AB  - Amelogenins are the main component of the developing enamel matrix. In placental
      mammals, amelogenins are rapidly cleaved following their secretion. HPLC
      fractionation of tooth extracts produces a complex chromatographic profile. The
      fractions are rich in amelogenin cleavage products that generally retain the
      amino-terminus of the parent protein but have varying lengths of peptide removed
      from the original carboxyl-terminus. In contrast, HPLC fractionation of opossum
      tooth extracts produces a simple profile with a single major chromatographic
      peak. SDS-and Western blot analyses demonstrated that most of the amelogenin
      consisted of a prominent protein band that migrated at 28 kDa. Mass spectroscopy
      confirmed the presence of two uncleaved, alternatively spliced forms of opossum
      amelogenin, Op202 and Op57, but did not detect major amelogenin cleavage products
      evident in tooth extracts from placental mammals. Amino acid composition analysis
      supported the conclusion that uncleaved amelogenin is the major component in the
      developing enamel matrix. Enzymogram analyses using gelatin, casein and
      recombinant amelogenin as substrates, comparing porcine, rat and opossum tooth
      extracts, suggested that fewer proteinases are present in opossum. These results
      identify potentially significant differences in the proteolytic processing of
      amelogenins between metatherian and eutherian mammals.

PMID- 9541246
TI  - Purification and sequencing of a 21 kDa and 25 kDa bovine enamel
      metalloproteinase.
AB  - The developing enamel matrix contains metalloproteinases that are presumed to
      have a role in hydrolysis of enamel matrix proteins. Determination of the
      identity and function of these proteinases requires further information such as
      their amino acid composition and sequence. In this study, we purified the 21 kDa
      and 25 kDa matrix metalloproteinase from secretory stage bovine enamel matrix.
      After extraction, these proteinases were further purified by sequential
      separation by ion exchange, Con A affinity chromatography, and reversed phase
      HPLC. The proteinases were separated by SDS PAGE, transferred to a PVDF membrane
      and the N-terminus was sequenced. The N-terminal sequences of both proteinases
      were the same, and showed homology to the porcine enamelysin (MMP 20) cDNA
      sequence. A cDNA for bovine MMP 20 was isolated from a bovine enamel organ cDNA
      library using a probe generated by PCR amplification. The coding regions of
      bovine and porcine MMP 20 cDNAs were highly homologous and contained the same
      regions of predicted amino acid sequence homology with the proteinase N-terminal
      sequences. These results suggest that the 21 kDa and 25 kDa enamel matrix
      metalloproteinases are cleavage products of the initially secreted MMP 20, and
      that the sequence for MMP 20 is conserved across species.

PMID- 9541248
TI  - Cementum attachment protein manifestation is restricted to the mineralized tissue
      forming cells of the periodontium.
AB  - The mechanisms that regulate cementogenesis are mainly unknown. A specific
      cementum attachment protein (CAP) has been recently partially characterized and
      found to be more efficient in supporting the attachment of alveolar bone cells
      (ABC) and periodontal ligament cells (PLC) than that of gingival fibroblasts
      (GF). The purpose of this study was to determine the capacity of human
      periodontal-derived cells to bind and express CAP and to relate these properties
      to their capacity to express alkaline phosphatase (AlP) and form mineralized
      tissue (MTF). ABC, PLC and GF were tested. Human stromal bone marrow cells (SBMC)
      and a cementoma-derived cell line (CC) served as controls. CAP binding was
      determined using 125I-CAP. The amount of MTF was assessed by alizarin red
      staining and image analysis determination of the amount of red-stained material.
      AlP and CAP expression were examined by histochemistry and immunochemistry,
      respectively. The highest expression of CAP was observed in CC, followed by PLC
      and ABC in decreasing order, whereas SBMC and GF did not express CAP. SBMC
      manifested the highest CAP binding capacity followed by CC, ABC, PLC and GF. MTF
      and AlP manifestation were greatest in SBMC, followed by ABC, PLC and CC.
      Collectively the results indicate that CAP binding and secretion are not linked
      and that CAP manifestation is restricted to periodontal derived cell lineages
      with the potential of forming mineralized tissues.

PMID- 9541247
TI  - Isolation of murine cementoblasts: unique cells or uniquely-positioned
      osteoblasts?
AB  - While cementoblasts express a number of mineral-related proteins, including bone
      sialoprotein (BSP), osteopontin (OPN) and osteocalcin (OC), these proteins do not
      appear to be expressed by cells of the intermediate dental follicle/periodontal
      ligament (PDL). This information was utilized in an experimental strategy to
      isolate presumptive cementoblasts from the root surface of day 24 murine
      mandibular first molars. Using microscopic dissection techniques, molars were
      carefully extracted from their alveolar crypts and subjected to trypsin
      collagenase digestion to remove adherent cells. Primary cultures were established
      and assayed for expression of proteins known to be expressed by cementoblasts at
      this timepoint in vivo (i.e. BSP, OPN, OC) and also an odontoblast-specific
      protein (i.e. DSP) to rule out contamination by pulpal cells. A subgroup of cells
      were found to express Type I collagen (89% of cells), BSP (46%), OPN (23%) and OC
      (30%); DSP was not detected within these cultures. We propose that cells within
      this heterogeneous population, which express this profile of osteogenic proteins,
      represent cementoblasts. The availability of a cementoblast cell line will make
      possible rigorous and controlled in vitro analysis of these cells and allow for
      determination of the unique characteristics of these cells not shared with other
      cells, particularly osteoblasts.

PMID- 9541249
TI  - Crystallite arrangement of hydroxyapatite microcrystals in human tooth cementum
      as revealed by electron paramagnetic resonance (EPR).
AB  - Human dental cementum was analyzed by electron paramagnetic resonance (EPR). The
      measured EPR powder spectra of gamma-irradiated cementum resembled those of gamma
      irradiated enamel. Both spectra were characterized by the same line shapes and g
      values. The position of the extreme first derivate peaks can be described by g1 =
      2.0023 and g2 = 1.9971 +/- 0.0002, and are assignable to the CO3(3-) center. The
      angular dependence of the cementum EPR spectra indicates a different arrangement
      of the hydroxyapatite microcrystals compared to that of enamel. A corresponding
      model of cementum microcrystal alignment has been proposed. The methodology
      presented can be utilized for studying the mineralization process of root
      cementum and other mineralized tissues.

PMID- 9541250
TI  - Formation of reparative acellular extrinsic fiber cementum in relation to implant
      materials installed in rat periodontium.
AB  - The aim of the present study was to determine the nature of the cells associated
      with the formation of reparative acellular extrinsic fiber cementum (AEFC).
      Calcifying collagen membranes, hydroxyapatite particles and/or non-resorbable
      ePTFE membranes were implanted in lesions made in the periodontium of the rat
      mandibular incisor. The incisor was prevented from erupting further, and the
      animals were killed after 1-8 wk. In the first week, next to cells with a
      fibroblastic phenotype, epithelial cells (ECs) migrating out of the reduced
      enamel epithelium were among the cells colonizing the wounds. From 2 wk on, the
      ECs showed regressive changes and disappeared. Along mineralized implant
      surfaces, a basophilic layer enriched in osteopontin (but without detectable
      amelogenin) was deposited. After 3 wk (when ECs were no longer present) the
      healing tissue transformed into a well-organized PDL-like tissue, and AEFC
      started to develop. Along the non-mineralizing ePTFE membranes, AEFC did not form
      except in regions where small calcified bodies were present. It is concluded that
      reparative AEFC layers are formed only along calcified surfaces. The cells
      associated with this reparative activity are periodontal ligament cells with a
      fibroblastic phenotype.

PMID- 9541251
TI  - Changes in the cytoskeleton of cells within the periodontal ligament and dental
      pulp of the rat first molar tooth during ageing.
AB  - The periodontal ligament and dental pulp connective tissues are foetal-like, and
      their process of ageing may therefore differ from other tissues of mesenchymal
      origin. Several studies have already highlighted the lack of age changes in the
      extracellular matrix (ECM), but more needs to be known about cellular changes.
      For this study, tissues from the first molar teeth of Wistar rats aged 12 wk and
      104 wk were compared by immunolocalisation of cytoskeletal components. Tissues
      from the first molar were immunostained, employing a panel of 16 monoclonal
      antibodies against cytokeratins, vimentin, F-actin and tubulin. Within the pulp,
      labelling for vimentin in both odontoblasts and pulpal fibroblasts and F-actin in
      the cell processes of odontoblasts was detected at both ages but with marked
      reduction in labelling in the older tissue. Within the periodontal ligament,
      vimentin labelling was weaker in the aged tissue, especially nearer the cementum.
      More significantly, the fibroblasts of the aged periodontal ligament expressed
      cytokeratin 19. In contrast to reports of little age change to the ECM, the cells
      of the pulp, and particularly the periodontal ligament, show marked changes to
      their cytoskeletal components.

PMID- 9541252
TI  - Immunocytochemical detection of apoptosis in human odontoblasts.
AB  - Pulpal chamber size decreases on ageing due to primary and secondary dentin
      deposition. This work was designed to find out the consequences of this pulp
      chamber reduction on odontoblast number and distribution. Twenty-one healthy
      human premolars were equally divided into three groups from 11-, 12.5- and 14-yr
      old adolescents, respectively). The external and the internal perimeters of
      dentin were recorded on vestibulo-lingual sections, from buccal to lingual
      cemento-enamel junction using an image analysis system. Nuclei of the
      odontoblasts were recorded on 12 automatically selected fields. On nine erupted
      premolars (3 teeth from each 11-, 12.5- and 14-yr-old patients), apoptosis was
      detected by confocal microscopy using a modification of the original TUNEL
      method. Apoptotic cells were labeled in central pulp fibroblasts, perivascular
      endothelial cells, and in odontoblasts. When the pulp volume decreases due to
      primary dentin production, the decrease of the surface available for odontoblasts
      is compensated for by a multilayer distribution of cells. Secondary dentin
      deposition, associated with odontoblasts reorganization in a single layer,
      results in a hyperbolic decrease of the odontoblasts number. This decrease seems
      to result from a programmed cell death, which eliminates half of the odontoblasts
      over a 4-yr period.

PMID- 9541253
TI  - Blood vessels and nerve fibers in rat incisor pulp. Immunoelectron microscopic
      observation with anti-substance P antibody.
AB  - The distribution of nerve fibers with special reference to their positional
      relationship with blood vessels in the pulp of the rat mandibular incisor was
      investigated by light and electron microscopic immunohistochemistry using
      polyclonal anti-substance P antibody. In the center of the pulp, numerous
      immunoreactive nerve fibers with varicosities were found along larger blood
      vessels. In the periphery of the pulp, there were two layers of capillary plexus;
      an odontoblastic and a subodontoblastic. Many nerve fibers, showing varicosities,
      were located in the subodontoblastic region, and some revealed a close
      association with pericytes of capillaries of the subodontoblastic plexus. A few
      nerve fibers entered the odontoblast layer, but no nerve fibers were seen to be
      associated with the odontoblastic capillary plexus. The results suggest that the
      local regulation of blood flow takes place not only in larger blood vessels but
      also in the capillaries of the rat incisor pulp.

PMID- 9541254
TI  - SEM and EDS analysis of calcospherites in human teeth.
AB  - The present study was designed to characterize the morphology and composition of
      calcospherites in the coronal and root predentin of human permanent teeth by
      scanning electron microscopy (SEM) and scanning electron microscopy energy
      dispersive spectroscopy (SEM-EDS). Human incisors, premolars, and molars were
      used. The calcospherites in the coronal predentin were globular and 10-20 microm
      in diameter. The calcospherites in the root predentin were smaller and their
      shape was different. Polygonal calcospherites and stellate calcospherites were
      observed in the intermediate region of the root predentin. Calcospherites were
      rarely present in the apical region of the root predentin. Calcified matrix
      fibers were observed in the apical region of the root predentin. The Ca/P molar
      ratio in crown calcospherites (1.63 +/- 0.27) differed significantly from that in
      root calcospherites (1.46 +/- 0.28). Sulfur was detected from the cervical region
      to the root region, but not in the horn region. Odontoblast activity and the
      local environment of the predentin are thought to determine the shape, size, and
      composition of calcospherites.

PMID- 9541255
TI  - Effect of CSF-1 on in vivo expression of c-fos in the dental follicle during
      tooth eruption.
AB  - It has been demonstrated that both colony-stimulating factor-one (CSF-1) and the
      transcription factor, c-fos are required for tooth eruption. Osteopetrotic mutant
      rats deficient in CSF-1 activity have unerupted teeth which can be induced to
      erupt by injections of CSF-1, and osteopetrotic mice deficient in c-fos, have
      unerupted teeth. Both CSF-1 and c-fos are expressed and translated in the dental
      follicle, the tissue that is required for eruption. Recent in vitro studies
      indicate that CSF-1 can enhance the expression of the c-fos gene in cultured
      dental follicle cells, but the effects in vivo are not known. In the present
      studies. postnatal rats were injected with 10(6) units of CSF-1 at different ages
      from birth to day 10 and sacrificed 30 min after injection. Isolation of total
      RNA from the follicle and reverse transcription PCR showed that CSF-1 injection
      enhanced the expression of c-fos over the non-injected controls. Chronologically,
      day 3 postnatally appeared to show the greatest increase of c-fos mRNA following
      CSF-1 injection. These results suggest that one of the functions of CSF-1 in
      tooth eruption is to enhance the early expression of c-fos. In turn, c-fos might
      act to promote fusion of monocytes into the osteoclasts needed for alveolar bone
      resorption and tooth eruption.

PMID- 9541256
TI  - Analysis of intracellular osteopontin as a marker of osteoblastic cell
      differentiation and mesenchymal cell migration.
AB  - Formation and repair of the hard and soft connective tissues of teeth and their
      supporting structures require stem cells to divide, differentiate and migrate to
      generate specific tissues in a defined temporo-spatial sequence. We have used
      antibodies to osteopontin (OPN) and fluorescence-activated cell sorting (FACS) to
      determine the relationship between OPN expression and cell differentiation in
      cultures of fetal rat calvarial cells. At different stages of osteogenic
      differentiation, OPN was expressed by 60-98% of cells. Populations of small OPN
      negative cells with low cellular granularity (S cells) were isolated and shown to
      be enriched in stem cells, characterised by a lack of differentiation markers,
      high proliferative potential, capacity for self renewal and multipotentiality.
      Within 24 h of plating, S cells attached, spread and started expressing OPN,
      CD44, and collagens types I, II and III. Confocal microscopy of OPN in
      differentiating cells revealed two distinct phenotypes; a perinuclear
      distribution, characteristic of secreted OPN, and an intracellular perimembranous
      distribution co-localising with the CD44 receptor, characteristic of migrating
      cells in which OPN was increased > 10-fold as measured by immunoblotting. These
      studies show that OPN is expressed early in mesenchymal cell differentiation and
      is related to cell migration as well as osteogenesis.

PMID- 9541257
TI  - Characteristics of vitamin D3 receptor (VDR) binding to the vitamin D response
      element (VDRE) in rat bone sialoprotein gene promoter.
AB  - Bone sialoprotein (BSP) is a mineralised tissue-specific protein that is highly
      expressed during the initial formation of bone and cementum. Expression of BSP is
      suppressed by the osteotropic hormone, 1,25-dihydroxyvitamin D3 (vitamin D3),
      which regulates bone remodelling. In previous studies, we have identified a
      vitamin D response element (VDRE) that is integrated with a novel inverted TATA
      box in the rat BSP promoter which mediates the suppression of BSP transcription
      (1). Although the nucleotide sequences of VDREs in different genes conform to a
      direct (hexamer) repeat, spaced by three nucleotides, the precise sequences are
      unique for each VDRE. To determine whether the nucleotide differences in the VDRE
      influence VDR binding, we have compared interactions of VDR proteins with various
      VDREs using gel mobility shift analysis. Both natural and recombinant VDRs bound
      to rat BSP and both mouse and porcine osteopontin (OPN) VDRE oligonucleotides in
      a concentration-dependent manner with a strong preference for dimer formation,
      whereas equal amounts of dimer and monomer were bound to the human osteocalcin
      VDRE. However, whereas a truncated VDR comprising the DNA binding domain alone
      bound the mouse osteopontin VDRE, it failed to interact with the porcine OPN and
      rat BSP VDREs. VDR binding to the BSP was sequence specific, as shown by
      mutagenesis analysis, and could be abolished by heat and VDR antibody. These
      studies demonstrate that subtle differences in the nucleotide sequence of VDREs
      affect VDR binding, which mediates the vitamin D3 response.

PMID- 9541258
TI  - Osteonectin RNA and collagen alpha1(I) RNA in the developing rat maxilla.
AB  - The sequence of rat osteonectin mRNA was determined. Comparison with osteonectin
      (ON) mRNA sequences of other vertebrates showed a great similarity, but a stretch
      of codons deviated with respect to another rat strain, suggesting the possibility
      of two ON variants in rats. Northern blots exhibited one band of ON mRNA only.
      The expression of ON and collagen alpha1(I) RNA in tissues of the developing rat
      maxilla was studied by in situ hybridization. Both ON and collagen alpha1(I) RNA
      were observed concomitantly in osteoblasts, starting from the onset of bone
      formation at day 17 post coitum through the oldest age examined, day 20 after
      birth. A strict co-expression of the two sequences was also observed in
      odontoblasts as well as in fibroblasts of the periodontal ligament. In
      ameloblasts, neither ON nor collagen alpha1(I) RNA was detected under stringent
      hybridization conditions, but lower stringency led to an ON signal. Considering
      that ON is a secretory protein and the high stability of the ON mRNA, the co
      expression of collagen alpha1(I) and ON RNA sequences in matrix-forming cells
      provided evidence that ON is a substantial component of collagen matrices.

PMID- 9541259
TI  - Activated adult human alveolar bone cells: a new model of matrix mineralization.
AB  - Activated adult human alveolar bone cells were isolated from 2-wk-old osteogenic
      tissue recuperated from dental implant surgeries following a two-step procedure.
      Osteogenic tissues were cultured as explant for 2 months. Cells began to migrate
      in the first 3 d and were confluent in 3-4 wk. However, adjacent to the explants,
      multicellular cell layers began to form in 10 d, and matrix mineralization was
      observed by 4 wk in these areas. These formations enlarged and by the end of the
      culture period, large diffuse matrix mineralization areas were observed. Light
      and electron microscopic observations confirmed the presence of a collagen matrix
      undergoing a mineralization process but showing important differences with the
      mineralized matrix tissue formed with a rat embryo calvaria bone cell system.
      This new model, using activated human alveolar bone cells, may provide a tool to
      investigate alveolar bone development and physiology and to set up new
      therapeutic approaches.

PMID- 9541260
TI  - Microradiographic aspects of the growing mandibular body during permanent
      premolar eruption in the dog.
AB  - In order to explore the bony changes in the mandibular body during prefunctional
      intraosseous eruption of premolars, 18 dogs aged from 8 to 16 wk at the beginning
      of experimental period, were given two intraperitoneal injections of
      oxytetracycline (50 mg/kg and 35 mg/kg 2 wk later) and 2 wk later a final
      injection of Alizarin red S (70 mg/kg). Microradiographic and fluorescent light
      microscopy studies showed that changes of the alveolar bony crypt walls were
      influenced by the growing dental germs which they surrounded. The cervical
      volumetric reduction, which indicates the end of crown formation, induced the
      apposition of lamellar and then woven bone on the adjacent alveolar walls.
      Furthermore, with occlusal displacement of the dental crown, the space below the
      tooth was immediately filled with woven bone trabeculae and chondroid tissue. The
      same phenomenon was observed at the level of the alveolar base, when the speed of
      tooth eruption was greater than that of root growth. During premolar development,
      the changes in the dental germ produces accommodating changes in the adjacent
      alveolar bone walls, and mandibular transversal growth has the same
      characteristics as that of a growing diaphysis.

PMID- 9541261
TI  - Evolution of patterns and processes in teeth and tooth-related tissues in non
      mammalian vertebrates.
AB  - The evolutionary links that exist between odontodes and organs that are
      phylogenetically related to them (teeth and scales) suggest the use of
      comparative approaches to study these structures. Part one of this review briefly
      introduces current ideas on how the pattern of odontodes and odontode-derived
      tissues has been established during evolution to yield the diversity of odontode
      related organs currently observed in nature in the cranial and postcranial
      skeleton. This introductory survey is used to highlight aspects of the
      developmental processes underlying the formation of some of these organs and the
      resemblance their development bears to odontogenesis. Part two provides a concise
      survey of the diversity of tooth structure in the different classes of extant
      vertebrates, in particular with reference to enamel/enameloid and dentine
      structure, and tooth attachment. Against this background, the current state of
      knowledge is reviewed with regard to developmental mechanisms involved in non
      mammalian odontogenesis. Common structure and similarities in development
      demonstrate that teeth and odontode derivatives should not be considered subjects
      of separate lines of research. On the contrary, results acquired in one of these
      fields are relevant to the other and may disclose model species that are relevant
      to studies on mammalian odontogenesis.

PMID- 9541262
TI  - Evolutionary origins of the vertebrate dentition: phylogenetic patterns and
      developmental evolution.
AB  - The theory that teeth evolved from dermal denticles linked with the origin of
      jaws no longer accounts for the diversity of new data emerging from the fossil
      record. We have reviewed oropharyngeal dental patterns in all fossil groups of
      early vertebrates to establish the primitive condition, in order to understand
      the polarity of change. The evolutionary precedence of dermal denticles before
      teeth now seems less likely; both may be alternative manifestations of a common
      morphogenetic system. This developmental system involves regulatory changes
      affecting the odontode, a fundamental exoskeletal unit, and can explain skeletal
      diversity. However, tooth and denticle differences may have diverged at loci deep
      within vertebrate phylogeny, as real differences exist between them. Teeth were
      conceived as evolving from non-growing odontodes with regulation of precise
      increase in size, position, sequence of time of development, and polarity of
      shape. A characteristic feature of teeth is the ability to replace from a
      developing sequence, programmed with these parameters, prior to demand. Tooth
      whorls, a feature of denticles in the oropharyngeal region, may be regarded as a
      preadaptation of this tooth replacement mechanism. The new fossil evidence
      suggests that teeth may have evolved from these more specialised oropharyngeal
      denticles in agnathan vertebrates.

PMID- 9541263
TI  - Evolution of the amelogenin gene in toothed and toothless vertebrates.
AB  - Amelogenin proteins constitute the major organic contents in forming enamel, but
      some previously published data indicate that the amelogenin gene could be present
      in several species lacking teeth or functional enamel. Therefore, amelogenin
      could have another, still unknown, function other than contributing to enamel
      formation. In order to test this hypothesis, the presence of this gene has been
      searched for in various vertebrates. We first compared the mammalian amelogenin
      sequences available in the literature to obtain the best chance of a successful
      detection of this gene in phylogenetically distant species. Using this analysis,
      we have shown that the occurrence of the amelogenin gene in the Y chromosome of
      primates and of an artiodactyl species is probably due to two independent
      duplications from genes on the X chromosome. Primers for PCR have therefore been
      synthesized and tested in eight species, five possessing teeth (human, two
      phylogenetically distant lizards, and two phylogenetically distant
      actinopterygians) and three lacking teeth (chicken and two phylogenetically
      distant turtles). The amelogenin gene has been detected in all species except
      those lacking teeth. This result indicates that the unique role of amelogenin in
      amniotes is to contribute to enamel formation.

PMID- 9541264
TI  - Degeneration of tooth germ in the developing dentition of the gray short-tailed
      opossum (Monodelphis domestica).
AB  - The aim of this study was to examine the developmental aspects of the dental
      lamina and the tooth germ of the marsupial opossum (Monodelphis domestica), and
      to clarify the dental formula of this animal. Specimens were 12-, 16-, and 18-d
      old opossums. 3-D reconstructions were constructed from frontal serial sections.
      In these animals, the tooth germs of the deciduous maxillary and mandibular
      canine, deciduous third premolar and first molar, and the deciduous maxillary
      first incisor and second molar had a successional dental lamina and a replacement
      tooth germ. The tooth germ of the deciduous maxillary fourth incisor and the
      mandibular first incisor were reduced. The dental lamina was continuous in each
      jaw except for the deciduous maxillary first incisor. The first dentition
      (deciduous dentition) remained as the permanent dentition on the deciduous
      maxillary first incisor, and the deciduous maxillary and mandibular canine and
      first molar. The maxillary fourth incisor and the mandibular first incisor were
      the second dentition (successional dentition). Only the deciduous third premolars
      were replaced. These results showed monophyodonty caused by both deciduous and
      replacement tooth germ degeneration.

PMID- 9541265
TI  - Activity of alkaline and acid phosphatases in dental epithelial cells and
      enameloid during odontogenesis in two teleost fish, Oreochromis niloticus and
      Tilapia buttikoferi.
AB  - The dental epithelial cells and enameloid at the stages of enameloid matrix
      formation, mineralization and maturation in the teleosts Oreochromis niloticus
      and Tilapia buttikoferi were investigated by means of enzyme histochemistry in
      order to identify their functions associated with the structural modification. No
      marked enzyme activities were found in the inner dental epithelial cells in the
      stage of enameloid matrix formation, although the outer dental epithelial cells
      often exhibited moderate alkaline phosphatase (ALPase) activity. In the stages of
      enameloid mineralization and maturation, the inner dental epithelial cells, which
      possessed a ruffled border at the distal ends, showed intense ALPase activity at
      their lateral and proximal cell membranes. At the same time, many acid
      phosphatase (ACPase)-positive vesicles and granules were localized at the distal
      cytoplasm of the inner dental epithelial cells. The outer dental epithelial
      cells, which contained well-developed labyrinthine canalicular spaces, showed
      neither marked ALPase nor ACPase activity. It is postulated that the dental
      epithelial cells in these two teleosts are mainly involved in the removal of the
      organic matrix from the enameloid, and in material transport to the enameloid
      during the later half of odontogenesis.

PMID- 9541266
TI  - Innervation of the periodontal ligament in the alligatorid Caiman crocodilius.
AB  - The mode of development and structure of crocodilian teeth and periodontium
      parallels that of mammals, but the teeth are continuously replaced throughout the
      lifetime of those animals. In this report, the innervation and fibres of the
      crocodilian periodontal ligament were examined using histology,
      immunohistochemistry for S-100 protein and transmission electron microscopy.
      Crocodilian periodontal ligaments had the following characteristics: (1)
      horizontal fibres, which connect the alveolar bone to the root cementum and (2)
      longitudinal fibres, which ran parallel to the tooth axis, with nerves and blood
      vessels in the middle layer of the ligament. The apex of root and tooth germs
      were both embedded in thick circular fibres. S-100 protein was detected in neural
      elements including terminal portions which were densely distributed in the
      periodontal ligament and dental follicle. The S-100 positive neural elements
      formed a periodontal plexus. We found two types of nerve endings; free endings
      and simple encapsulated corpuscles as described in mammals. The presence of such
      nerve endings in caiman suggests that these teeth, in addition to having a biting
      function, may also act as highly sensitive sensory organs.

PMID- 9541267
TI  - Molecular approaches to renal physiology and therapeutics.
AB  - The recent development of methods to transfer, mutate, or ablate genes in vivo
      has provided renal investigators and physicians with powerful tools to explore
      normal renal physiology, the pathophysiological basis of renal disease, and
      potential therapeutic interventions. The use of transgenic and knockout mice to
      produce gain-of-function and loss-of-function mutations, and to create animal
      models of human hereditary renal diseases, permits unprecedented versatility and
      power of experimental design. Conditional and inducible gene targeting methods to
      control the temporal and spatial expression of transgenes offer considerable
      promise in studying the impact of normal and disease genes in the kidney. In vivo
      gene transfer of encoding DNAs, antisense DNA and RNA, and cis-element decoys
      allows manipulation of specific genes in somatic cells. Liposome-mediated,
      virally mediated, and ex vivo transduced renal cells represent novel approaches
      to facilitate in vivo gene transfer to the kidney.

PMID- 9541268
TI  - Optical methods in renal research.
AB  - Light microscopy is a powerful experimental approach that allows the researcher
      to study the dynamics of cellular responses and subcellular organization. Recent
      advances in optics, detectors, computerized image processing, and the development
      of vital dyes promise to extend the utility of light microscopy. Quantitative
      approaches measuring intracellular pH, sodium or calcium are well known, but
      future developments may permit quantitative analysis of immunolabeled specimens.
      This review will describe the basic features of light microscopes and imaging
      techniques. Specific types of microscopy such as confocal microscopy, wide field
      microscopes, and epifluorescence microscopy will be considered. In addition,
      recent advances in cellular labeling techniques will be described. Post
      production image processing techniques and computerized deconvolution methods
      will be discussed, and lastly future developments in optics, improved sensitivity
      in detectors with enhanced signal-to-noise ratios will be explored. Wherever
      possible, specific applications that have been applied to renal physiology
      studies will be cited.

PMID- 9541269
TI  - Structure and function of the Mec-ENaC family of ion channels.
AB  - The epithelial sodium channel (ENaC) is the prototype of a new family of ion
      channels known as the Mec-ENaC superfamily. This new family of proteins are
      involved in a wide variety of functions that range from maintenance of sodium
      homeostasis to transduction of mechanical stimuli and nociceptive pain by
      specialized neurons. They show distinct tissue- and cell type-dependent
      expression and differential sensitivity to inhibition by the diuretic amiloride
      and its analogs. Despite the very little amino acid identity shared by these
      proteins, they all have the same common structure that has become a hallmark of
      the Mec-ENaC superfamily. The efforts to understand the structure and regulation
      of these ion channels have been stimulated by the recent discovery of severe
      disturbances in the maintenance of blood pressure caused by gain- or loss-of
      function mutations in the genes that encode the subunits of ENaC in humans.
      Moreover, cloning of the ion channels that mediate pain elicited by tissue injury
      and inflammation will facilitate the development of new drugs to treat these
      common ailments.

PMID- 9541270
TI  - Protein targeting: the molecular basis of vectorial transport in the kidney.
AB  - The renal tubular epithelium maintains different sets of transport proteins in
      plasma membrane domains facing the lumenal and mucosal fluids and limits
      diffusion between these two compartments. This asymmetry is generated by
      directing transporters to the appropriate membrane domain, a process that
      requires both an intracellular machinery that sorts out proteins destined for
      different domains and cues that create the addresses to which these proteins are
      sorted. Interactions with the extracellular environment convey the positional
      information that creates the plasma membrane domains. These interactions are
      mediated by macromolecular assemblies of cell adhesion molecules, cytoskeleton,
      and signaling molecules. This review focuses on the mechanisms by which these
      complexes create polarized membrane domains.

PMID- 9541271
TI  - Recent advances in water transport.
AB  - Complex organisms regulate the osmolalities of their compartments by limiting
      water flow across some membranes and promoting rapid water flow across others via
      proteins called aquaporins. Barrier epithelia limit water flow by reducing the
      mobilities of fatty acid chains in their apical membranes, especially in the
      outer leaflets of these membranes. Aquaporins are 28 to 30 kDa, 6 membrane
      spanning proteins that are expressed in a wide variety of organisms from bacteria
      to plants to mammals. The structural and biophysical data are summarized to
      develop our best understanding of water pore function. In addition, the
      regulation of trafficking of AQP 2 into and out of the apical membranes of
      collecting duct principal cells is described.

PMID- 9541272
TI  - Calcium signals and calcium channels in osteoblastic cells.
AB  - Calcium (Ca2+) channels are present in non-excitable as well as in excitable
      cells. In bone cells of the osteoblast lineage, Ca2+ channels play fundamental
      roles in cellular responses to external stimuli including both mechanical forces
      and hormonal signals. They are also proposed to modulate paracrine signaling
      between bone-forming osteoblasts and bone-resorbing osteoclasts at local sites of
      bone remodeling. Calcium signals are characterized by transient increases in
      intracellular Ca2+ levels that are associated with activation of intracellular
      signaling pathways that control cell behavior and phenotype, including patterns
      of gene expression. Development of Ca2+ signals is a tightly regulated cellular
      process that involves the concerted actions of plasma membrane and intracellular
      Ca2+ channels, along with Ca2+ pumps and exchangers. This review summarizes the
      current state of knowledge concerning the structure, function, and role of Ca2+
      channels and Ca2+ signals in bone cells, focusing on the osteoblast.

PMID- 9541273
TI  - Growth factors and acute renal failure.
AB  - During acute renal injury, there are alterations in the expression of several
      growth factors and their receptors in the kidney. The increased expression of
      several growth factors and/or their receptors at sites of nephron injury suggests
      important contributions to repair. Exogenous administration of some growth
      factors, such as IGF-I, EGF and HGF, accelerates recovery of renal function in
      experimental acute renal failure (ARF). In ARF growth factors act through several
      mechanisms, which may include altered cell cycle regulation and mitogenesis,
      differentiation of recovered cells, regulation of apoptosis, improved renal
      hemodynamics, and others. There is evidence for interactions of growth factors
      with other growth factors as well as with other genes resulting in complex
      orchestration of biologic events contributing to recovery from ARF.

PMID- 9541274
TI  - Recent insights into the roles of nitric oxide and renin-angiotensin in the
      pathophysiology of preeclamptic pregnancy.
AB  - Normal pregnancy involves marked maternal hemodynamic adaptations; these are
      suppressed in preeclampsia, leading to serious complications for mother and baby.
      The cause of preeclampsia is unknown, but may involve primary pathology at the
      maternal/fetal interface. However, the systemic manifestations of the disease are
      associated with widespread maternal vascular endothelial damage and dysfunction.
      There has been considerable recent interest in the possible roles for nitric
      oxide (NO) deficiency and for alterations in the renin angiotensin system (RAS)
      in the pathophysiology of preeclampsia. The following is an overview of the
      hemodynamic responses to normal pregnancy, an evaluation of the possible roles of
      NO and the RAS in these adaptations, and a review of the important aspects of
      these systems in preeclampsia.

PMID- 9541275
TI  - The actions of NO in the central nervous system and in thymocytes.
AB  - Nitrogen monoxide (NO) has been suggested to be involved in many physiological
      and pathological functions. In rat hippocampus, chemical NO donors stimulated
      noradrenaline release in the presence of thiols such as dithiothreitol and L
      cysteine. S-Nitrosocysteine, which is proposed to be a stable and endogenous S
      nitrosothiol molecule, stimulated noradrenaline release by itself. The effect of
      S-nitrosothiol on noradrenaline release was calmodulin-dependent and cyclic GMP
      independent. S-Nitrosocysteine was incorporated into the slice via the L-type
      like amino acid transporter. These findings suggest the physiological
      significance of S-nitrosocysteine on neurotransmitter release and propose the
      existence of a specific uptake system of S-nitrosothiols in neuronal tissues. In
      rat thymocytes, chemical NO donors inhibited DNA synthesis. Hydrocortisone
      treatment in vivo inhibited DNA synthesis via the expression of the inducible NO
      synthase protein, and the accumulation of NO and cyclic GMP. Although it is known
      that glucocorticoids regulate inducible NO synthase expression negatively in
      several types of cells in vitro, glucocorticoid treatment in vivo regulates the
      expression positively. In primary cultured rat glial cells, a combination of
      cytokines stimulated production of nitrite via expression of inducible NO
      synthase. In these cells, simultaneous addition of endothelin decreased inducible
      NO synthase expression induced by cytokines. On the other hand, pretreatment with
      endothelin for 24 hr enhanced the inducible NO synthase expression. Endothelin
      has two effects on inducible NO synthase expression, positive and negative,
      depending on treatment time. The actions of NO on the hippocampus and thymocytes
      and the regulation of inducible NO synthase expression in glial cells are
      discussed.

PMID- 9541276
TI  - Effect of PP1D-1, a synthetic antiplatelet compound, on rabbit platelets.
AB  - The antiplatelet mechanism of a synthetic compound, 2-chloro-3
      methoxycarbonylpropionamido-1,4-naphthoquinone (PP1D-1), was studied by employing
      washed rabbit platelets in vitro. PP1D-1 concentration-dependently inhibited
      thrombin (0.1 U/ml)-, platelet-activating factor (2 ng/ml)-, collagen (10
      microg/ml)-, arachidonic acid (100 microM)- and U46619 (1 microM)-induced
      aggregation and ATP release in washed rabbit platelets. The IC50 values of PP1D-1
      for aggregation induced by the above inducers are 17.9+/-1.7, 9.8+/-1.1, 3.9+/
      0.4, 1.8+/-0.3 and 1.7+/-0.3 microM, respectively. PP1D-1 did not affect platelet
      thromboxane B2 or prostaglandin D2 formation induced by arachidonic acid,
      indicating that it did not affect cyclooxygenase and thromboxane synthase
      activities. PP1D-1 significantly inhibited the formation of inositol 1,4,5
      trisphosphate caused by these five platelet stimulators. Moreover, PP1D-1
      inhibited the increase in intracellular calcium concentration induced by these
      agents. On the contrary, PP1D-1 did not inhibit thapsigargin-elevated
      intracellular calcium concentration in indomethacin-pretreated platelets,
      indicating it did not influence the effect of thapsigargin. According to these
      data, PP1D-1 exerts antiplatelet effects mainly by inhibiting phosphoinositide
      turnover.

PMID- 9541277
TI  - Shortening of monophasic action potential duration during hyperkalemia and
      myocardial ischemia in anesthetized dogs.
AB  - The elevation of the myocardial extracellular potassium concentration ([K+]o) is
      known to shorten action potential duration, which may lead to the occurrence of
      arrhythmias. The aim of this study was to compare the mechanisms responsible for
      the shortening of monophasic action potential duration (MAPD) in hyperkalemic and
      myocardial ischemic hearts in anesthetized dogs. During a venous infusion of KCl
      for 5 min, [K+]o was increased and MAPD was significantly shortened. The ATP
      sensitive K+ (K[ATP]) channel blocker glibenclamide did not affect the shortening
      of MAPD during KCl-infusion, indicating that K(ATP) channels are not involved in
      this mechanism. During 5-min occlusion of the left anterior descending coronary
      artery, [K+]o was increased, myocardial pH was decreased and MAPD was shortened.
      Glibenclamide completely abolished the shortening of MAPD, while partial
      elevation of [K+]o remained even in the presence of glibenclamide. This suggests
      that the shortening of MAPD is dependent mainly on the activation of K(ATP)
      channels. Both models in the present study demonstrate that different types of
      potassium channels are involved in the regulation of action potential duration.

PMID- 9541278
TI  - Effects of YM175, a new-generation bisphosphonate, on hypercalcemia induced by
      tumor-derived bone resorbing factors in rats.
AB  - YM175 (disodium cycloheptylaminomethylenediphosphonate monohydrate) is a new
      generation bisphosphonate with stronger inhibitory activity on bone resorption
      than first-generation bisphosphonates. In the present study, the effect of YM175
      on hypercalcemia induced in rats by single administration of either parathyroid
      hormone-related protein (PTHrP) or concomitant administration of PTHrP and
      interleukin 1beta (IL-1beta) was investigated. YM175 (0.01-1 mg/kg, i.v.)
      inhibited the increase in serum free calcium concentration induced by continuous
      administration of PTHrP alone (3 microg/rat/day, s.c., 7 days) dose-dependently.
      The inhibitory effect of YM175 appeared the day after administration and remained
      3 days after administration. The effect of YM175 reached a maximum 2 days after
      administration, at which time the ED50 value of YM175 was calculated to be 0.041
      mg/kg, i.v., revealing a potency approximately 50- and 10-fold stronger than
      those of either pamidronate or alendronate, respectively. In contrast, elcatonin
      (1-10 units/kg, s.c.) only transiently inhibited PTHrP-induced free calcium
      increase. YM175 (0.1-3 mg/kg, i.v.) also inhibited the increase in the serum free
      calcium concentration induced by continuous concomitant administration of both
      PTHrP and IL-1beta in a dose-dependent manner. These results indicated that YM175
      is expected to be a useful drug for hypercalcemia associated with malignant
      tumors due to its efficacy and range of effect.

PMID- 9541280
TI  - Effect of tacrolimus hydrate (FK506) ointment on spontaneous dermatitis in NC/Nga
      mice.
AB  - The effect of tacrolimus hydrate (FK506) ointment on spontaneous dermatitis in
      NC/Nga (NC) mice was examined. FK506 ointment (0.1-1%) suppressed the development
      of dermatitis and was also therapeutically effective against established
      dermatitis. Increases in CD4-positive T cells (helper T cells), mast cells,
      eosinophils and immunostaining of interleukin (IL)-4, IL-5 and IgE were confirmed
      in the skin of the NC mice, and FK506 ointment suppressed all of these changes.
      Increased plasma IgE was also confirmed in the NC mice, and treatment with FK506
      ointment reduced the plasma IgE level. These results suggested that FK506
      suppressed the dermatitis by inhibiting the activation of inflammatory cells and
      by blocking the cytokine network in the skin of the NC mice. The commercially
      available steroid ointments showed only marginal effect on the development of
      dermatitis and showed some signs of side effects such as alopecia or atrophy of
      the skin. The effect of the steroids might have been masked by these side effects
      because the steroids showed similar inhibitory effects on the skin
      histopathological changes and the increase of plasma IgE. From these results,
      FK506 ointment can be expected to be a useful drug for atopic dermatitis.

PMID- 9541279
TI  - Proliferation of adult rat hepatocytes in primary cultures induced by platelet
      derived growth factor is potentiated by phenylephrine.
AB  - We investigated whether or not proliferation of adult rat hepatocytes induced by
      platelet-derived growth factor (PDGF) is affected by alpha1-adrenoceptor agonists
      such as phenylephrine during the early and late phases of primary culture. Adult
      rat hepatocytes underwent significant DNA synthesis after culture with 10 ng/ml
      of PDGF for 2 hr at a low cell density (3.3 x 10(4) cells/cm2). Under these
      culture conditions, the number of nuclei increased significantly during the 3.5
      hr culture period. Hepatocyte DNA synthesis and proliferation induced by 10 ng/ml
      of PDGF decreased slightly as a result of increasing the initial plating density.
      An alpha1-adrenoceptor agonist, phenylephrine (10(-6) and 10(-5) M), alone did
      not affect hepatocyte DNA synthesis and proliferation, but markedly potentiated
      PDGF-induced hepatocyte DNA synthesis and proliferation. The phenylephrine effect
      was mimicked by phorbol myristate acetate (10(-7) M), but not by ionomycin (10(
      5) M). The mitogenic effects of PDGF were almost completely blocked by treating
      hepatocytes with genistein (5 x 10(-6) M), U-73122 (3 x 10(-6) M), sphingosine
      (10(-5) M), wortmannin (10(-7) M) and rapamycin (10 ng/ml). These results
      demonstrate that PDGF can induce the proliferation of adult rat hepatocytes
      rapidly in primary culture, regardless of the initial plating density. The
      present results also suggest that following stimulation with PDGF, activation of
      tyrosine kinase, phospholipase C, phosphatidylinositol 3-kinase, protein kinase C
      (PKC) and p70 ribosomal protein S6 kinase is essential for the proliferation of
      adult rat hepatocytes. The co-mitogenic effects of phenylephrine may involve PKC
      activation.

PMID- 9541281
TI  - A novel angiotensin II-receptor antagonist, 606A, induces regression of cardiac
      hypertrophy, augments endothelium-dependent relaxation and improves renal
      function in stroke-prone spontaneously hypertensive rats.
AB  - It is well-known that cardiac hypertrophy and arterial and renal dysfunction are
      serious complications of hypertension. Therefore, we investigated the chronic
      effects of 606A (2-propyl-3-[2'(1H-tetrazole-5-yl)biphenyl-4-yl]methyl-5-acetyl
      4,5,6,7- tetrahydro imidazo [4,5-c]pyridine-4-carboxylic acid disodium salt), a
      novel AT1-receptor antagonist, on these complications of hypertension in stroke
      prone spontaneously hypertensive rats (SHRSP) using Wistar Kyoto rats (WKY) as
      the control. After 8 weeks treatment from 16 weeks of age with 606A by a
      subcutaneously implanted osmotic pump, cardiac function, cardiac weight,
      acetylcholine-induced endothelium-dependent relaxation in the isolated aorta and
      renal function were estimated. Furthermore, wall thickness of the left ventricle
      was studied morphologically. We found that 606A (0.3 mg, 1 mg and 3 mg/head/day)
      dose-dependently lowered blood pressure without any effects on heart rate in
      SHRSP. Long-term treatments with 606A significantly reduced cardiac weight, left
      ventricular wall thickness and left ventricular end diastolic pressure, whereas
      it did not affect cardiac contractility. Endothelium-dependent relaxation of the
      aorta was recovered, and total protein excretion as well as total protein
      excretion/creatinine excretion ratio was reduced to the level of WKY by the
      treatment. These results suggest that 606A not only has a hypotensive effect but
      also protects cardiac, renal and vascular tissues from complications of
      hypertension. Thus, 606A could be an useful drug for treatment of hypertension.

PMID- 9541282
TI  - Role of phosphodiesterase 4 isoenzyme in alkaline phosphatase activation by
      calcitonin in porcine kidney LLC-PK1 cells.
AB  - To confirm the intracellular signal transduction in regulation of alkaline
      phosphatase (ALP) activity by calcitonin in kidney tubular cells, effects of
      several inhibitors of cyclic nucleotide phosphodiesterase (PDE) isoenzymes and
      cyclic AMP-dependent protein kinase (PKA) on the action of salmon calcitonin in
      porcine kidney tubular epithelial cells LLC-PK1 were examined. A confluent
      culture of LLC-PK1 cells was treated with calcitonin and inhibitors in Dulbecco's
      modified Eagle's medium supplemented with 0.1% bovine serum albumin, and
      intracellular cyclic AMP content and ALP activity were measured after incubation
      for 30 min and 48 hr, respectively. Calcitonin and PDE 4 inhibitors increased
      cyclic AMP level and ALP activity in the cells, and PDE 4 inhibitors
      synergistically potentiated the effects of calcitonin. Calcitonin induced ALP
      activation by treatment for the first 1 hr, as well as continuous treatment for
      48 hr, while it never increased the enzyme activity just after 1-hr exposure.
      Rolipram, an inhibitor of PDE 4 isoenzyme, induced ALP activation by itself and
      in combination with calcitonin by only a long term treatment (48 hr). The
      activation of ALP by calcitonin and rolipram each alone and in combination was
      completely abolished by a PKA inhibitor, H-89. These results confirm that
      calcitonin induces ALP activation through the cyclic AMP-PKA pathway and that PDE
      4 isoenzyme is closely associated with the calcitonin-receptor system and plays a
      major role in hydrolysis of cyclic AMP produced in the kidney tubular cells.

PMID- 9541283
TI  - Effects of KW-5617 (zaldaride maleate), a potent and selective calmodulin
      inhibitor, on secretory diarrhea and on gastrointestinal propulsion in rats.
AB  - KW-5617 (zaldaride maleate), 1,3-dihydro-1-[1-[(4-methyl-4H,6H-pyrrolo[1,2
      a][4,1]-benzoxazepin -4-yl)methyl]-4-piperidinyl]-2H-benzimidazol-2-one maleate,
      is a selective calmodulin inhibitor. We studied the effects of KW-5617 on
      secretory diarrhea and gastrointestinal propulsion in rats, as compared with
      those of loperamide, a conventional anti-diarrheal drug. Diarrhea was induced in
      rats either by 16,16-dimethyl prostaglandin E2 (500 microg/kg, i.p.) or by castor
      oil (1 ml/100 g body weight, p.o.). In the 16,16-dimethyl prostaglandin E2 model,
      KW-5617 at the doses of 3 mg/kg (p.o.) and higher ameliorated the diarrhea.
      Similarly, loperamide improved the diarrhea, the activity of loperamide being
      equivalent to that of KW-5617. In the castor oil model, KW-5617 significantly
      delayed the onset of diarrhea at the doses of 3 mg/kg (p.o.) and higher, while
      loperamide delayed the onset of diarrhea at the doses of 0.3 mg/kg (p.o.) and
      higher. KW-5617 only at the high doses of 30 and 100 mg/kg (p.o.) reduced gastric
      emptying, small intestinal propulsion, proximal colonic propulsion and distal
      colonic propulsion. In contrast, loperamide at its anti-diarrheal doses inhibited
      gastrointestinal propulsion. Our results show that KW-5617, unlike loperamide, at
      its anti-diarrheal doses does not exert anti-propulsive effects in rats. KW-5617
      may be a useful drug for the treatment of diarrhea in terms of less side effects
      such as constipation.

PMID- 9541284
TI  - Studies on neuromuscular blockade by boldine in the mouse phrenic nerve
      diaphragm.
AB  - The effects of boldine [(S)-2,9-dihydroxyl-1,10-dimethoxy-aporphine], a major
      alkaloid in the leaves and bark of Boldo (Peumus boldus Mol.), on neuromuscular
      transmission were studied using a muscle phrenic-nerve diaphragm preparation.
      Boldine at concentrations lower than 200 microM preferentially inhibited, after
      an initial period of twitch augmentation, the nerve-evoked twitches of the mouse
      diaphragm and left the muscle-evoked twitches unaffected. The twitch inhibition
      could be restored by neostigmine or washout with Krebs solution. The twitches
      evoked indirectly and directly were both augmented initially, suggesting that the
      twitch augmentation induced by boldine was myogenic. Boldine inhibited the
      acetylcholine-induced contraction of denervated diaphragm dose-dependently with
      an IC50 value of 13.5 microM. At 50 microM, boldine specifically inhibited the
      amplitude of the miniature end plate potential. In addition, boldine was similar
      to d-tubocurarine in its action to reverse the neuromuscular blocking action of
      alpha-bungarotoxin. These results showed that the neuromuscular blockade by
      boldine on isolated mouse phrenic-nerve diaphragm might be due to its direct
      interaction with the postsynaptic nicotinic acetylcholine receptor.

PMID- 9541285
TI  - M2 and M3 muscarinic receptors couple, respectively, with activation of
      nonselective cationic channels and potassium channels in intestinal smooth muscle
      cells.
AB  - Smooth muscle cells of guinea pig ileum express both M2 and M3 subtypes of
      muscarinic receptors. Under voltage clamp, activation of the muscarinic receptors
      with carbachol (CCh) induces Ca2+-activated K+ current (I[K-Ca]) and nonselective
      cationic current (Icat). Receptor subtypes mediating the current responses were
      characterized by using pirenzepine, AF-DX116, 4-DAMP and atropine, which have
      different profiles of the affinity constants for muscarinic receptor subtypes.
      The muscarinic antagonists inhibited either CCh-evoked I(K-Ca) or Icat with
      different potencies. Their relative potencies for I(K-Ca) and Icat inhibition
      resembled the relative affinity constants for M3 and M2 subtypes, respectively.
      Thus, the I(K-Ca) is mediated via the M3 subtype and the Icat via the M2 subtype.

PMID- 9541286
TI  - Protective effect of MKC-231, a novel high affinity choline uptake enhancer, on
      glutamate cytotoxicity in cultured cortical neurons.
AB  - This study was performed to examine the neuroprotective action of 2-(2
      oxopyrrolidin-1-yl)-N-(2,3-dimethyl-5,6,7,8-tetrahydrofuro [2,3-b]quinolin-4
      yl)acetoamide (MKC-231), which enhances choline uptake and acetylcholine release
      in the central nervous system. Glutamate neurotoxicity was assessed with cortical
      cultures obtained from fetal rats. Exposure of cultures to MKC-231 for 12-24 hr
      ameliorated glutamate cytotoxicity. MKC-231 reduced cytotoxicity induced by
      ionomycin, a calcium ionophore, but did not affect the cytotoxicity induced by S
      nitrosocysteine, a nitric oxide (NO) donor. These findings suggest that MKC-231
      protects against glutamate neurotoxicity by suppressing the NO formation
      triggered by Ca2+-influx.

PMID- 9541287
TI  - Effect of oxatomide on experimental allergic rhinitis in guinea pigs.
AB  - We have investigated the effect of oxatomide, an antiallergic agent, on
      experimental allergic rhinitis in sensitized guinea pigs. Oxatomide (1 and 10
      mg/kg, p.o.) significantly inhibited the sneeze response and nasal rubbing after
      antigen challenge. Oxatomide (10 and 30 mg/kg) reduced the increase in nasal
      vascular permeability induced by the antigen-antibody reaction. The decreases in
      nasal cavity volume caused by nasal mucosal swelling 10 min, 30 min and 6 hr
      after antigen challenge were significantly inhibited by oxatomide (30 mg/kg).
      These results indicate that oxatomide inhibits the experimental allergic rhinitis
      in guinea pigs.

PMID- 9541288
TI  - Possible involvement of K(ATP) channel activation in depressor responses to
      vasoactive neuropeptides in rats.
AB  - I.v. bolus injections of vasoactive intestinal polypeptide (VIP) (0.3 or 1
      microg/kg), calcitonin gene-related peptide (CGRP) (0.3 microg/kg) or substance P
      (0.1 microg/kg) to anesthetized rats reduced blood pressure, accompanied by
      slight increases in heart rate. Cromakalim (0.3 microg/kg/min) infused i.v.
      significantly potentiated the depressor responses to VIP and CGRP, but not those
      to substance P and acetylcholine (ACh) (0.1 microg/kg). Glibenclamide (20 mg/kg,
      i.v.) significantly inhibited not only the depressor responses to VIP and CGRP,
      but also the augmentation of the effects of the two agents by cromakalim. These
      results suggest that the depressor responses to VIP and CGRP are mediated in part
      through K(ATP) channel activation.

PMID- 9541289
TI  - In vivo single-voxel proton MR spectroscopy in intracranial cystic masses.
AB  - PURPOSE: Our objective was to evaluate the proton MR spectroscopic pattern of the
      cystic contents of various intracranial masses and to report characteristic
      spectral patterns that may be helpful in the differential diagnosis of these
      lesions. METHODS: We evaluated 40 proton MR spectra obtained from cystic contents
      of various intracranial cystic masses in 39 patients, including gliomas (n = 14),
      metastases (n = 3), abscesses (n = 8), cysticercosis (n = 4), epidermoids (n =
      3), and others (n = 7). Proton MR spectroscopy was performed on a 1.5-T MR unit
      using a point-resolved spectroscopic sequence with a 2 x 2 x 2 cm3 volume of
      interest. Assignment of the resonance peaks was based on previous studies.
      RESULTS: Adequate proton MR spectroscopic data were obtained in 35 cases (88%).
      In most gliomas and metastases, only a lactate resonance was observed. There was
      a trend toward a higher lactate peak in high-grade gliomas. A few tumors,
      including malignant gliomas and metastases, showed lipid signal combined with
      lactate signal. In abscesses, there were various combinations of lactate,
      acetate, succinate, amino acids (including valine, alanine, and/or leucine),
      and/or unassigned resonances. In cysticercosis, resonances of lactate, succinate,
      alanine, acetate, and/or unassigned resonances were observed. Three epidermoid
      cysts showed only lactate signal. There were no identifiable resonances from the
      arachnoid and porencephalic cysts. CONCLUSION: Only lactate is commonly observed
      in a variety of intracranial cystic masses, except for abscess and cysticercosis,
      in which resonances of acetate, succinate, amino acids, and/or unassigned
      metabolites can be seen in addition to a lactate peak.

PMID- 9541290
TI  - Differentiating recurrent tumor from radiation necrosis: time for re-evaluation
      of positron emission tomography?
AB  - Our purpose was to evaluate the ability of FDG PET to differentiate recurrent
      tumor from posttherapy radiation necrosis. METHODS: MR images, PET scans, and
      medical records of 84 consecutive patients with a history of a treated
      intracranial neoplasm were evaluated retrospectively. In all patients, recurrent
      tumor or radiation necrosis was suggested by clinical or MR findings. Metabolic
      activity of the PET abnormality was compared qualitatively with normal
      contralateral gray and white matter. RESULTS: PET findings were confirmed
      histologically in 31 patients. With contralateral white matter as the standard of
      comparison, the PET scan sensitivity and specificity were found to be 86% and
      22%, respectively. With contralateral gray matter as the reference standard, the
      sensitivity and specificity became 73% and 56%, respectively. Overall, nearly one
      third of the patients would have been treated inappropriately in either scheme
      had the PET scan been the sole determinant of therapy. CONCLUSION: Our data
      suggest that the ability of FDG PET to differentiate recurrent tumor from
      radiation necrosis is limited. Both false-positive and false-negative PET scan
      results contributed to unacceptably low sensitivity and specificity values.

PMID- 9541291
TI  - Cisplatin neurotoxicity presenting as reversible posterior leukoencephalopathy
      syndrome.
AB  - Visual disturbance, hypertension, convulsions, and unconsciousness developed in a
      70-year-old man after cisplatin chemotherapy and upper-limb amputation for
      osteosarcoma. MR imaging revealed bilateral reversible abnormalities in the
      occipital, parietal, and frontal white matter. Clinical and neuroradiologic
      features corresponded to reversible posterior leukoencephalopathy syndrome
      (RPLS), which some immunosuppressive and chemotherapeutic drugs have been
      reported to trigger. Cisplatin may be among these drugs. Our patient also had
      hypomagnesemia, which may have figured in the pathophysiology.

PMID- 9541292
TI  - Surgical site after resection of a meningioma.
AB  - PURPOSE: Our goal was to characterize MR changes over time at the site of
      meningioma resection in order to determine optimal timing for detecting residual
      and recurrent tumor. METHODS: Twenty-one patients were studied with enhanced MR
      imaging during the first 5 postoperative days and additional studies were
      obtained 3 to 8 weeks after surgery (16 studies), 3 months to 1 year after
      surgery (17 studies), and 1 year or more after surgery (32 studies). Images were
      analyzed for residual tumor, membrane enhancement, parenchymal enhancement,
      edema, and blood collections. RESULTS: Early postoperative images showed
      extensive, thin membrane enhancement that thickened by 3 to 8 weeks after surgery
      and that thinned or resolved and became less extensive by 6 months or more
      postoperatively. Twelve of 20 patients with long-term follow-up studies had
      membrane enhancement. Thin, serpiginous foci of enhancement in the surgical bed
      were identified only on early postoperative studies and probably represent
      gradual thrombosis of feeding vessels. CONCLUSION: Residual foci of meningioma
      are best detected on studies obtained within the first 5 days after surgery
      because membrane thickness increases by 3 to 8 weeks after surgery and may
      obscure a small residual meningioma. Our study confirms the presence of prolonged
      membrane enhancement after surgery, although it thins with time and becomes
      confined to the craniotomy site.

PMID- 9541293
TI  - Cerebral MR imaging in intravascular lymphomatosis.
AB  - MR imaging data were reviewed retrospectively in four male patients (32 to 74
      years old) with histologically confirmed intravascular lymphomatosis (IVL), a
      rare, aggressive form of non-Hodgkin lymphoma. MR findings included infarct-like
      lesions (n = 2), focal parenchymal enhancement (n = 3), dural/arachnoid
      enhancement (n = 2), and, in one case, nonspecific, patchy foci of increased
      signal in the white matter on long-TR images. All patients had multifocal
      lesions. Knowledge of the spectrum of MR imaging features in this unusual
      disorder may aid in diagnosis and potentially enhance the role of imaging in
      following response to therapy.

PMID- 9541294
TI  - Alteration of cerebral blood flow in patients with bacterial and viral
      meningoencephalitis.
AB  - PURPOSE: Our purpose was to investigate cerebral blood flow disturbances in
      patients with bacterial and viral meningoencephalitis. METHODS: Forty-two
      patients with acute bacterial and viral meningoencephalitis and 14 control
      subjects were studied using 99mTc-hexamethylpropyleneamine oxime (HMPAO) single
      photon emission computed tomography (SPECT). SPECT images were evaluated
      semiquantitatively. The results were compared with clinical severity of the
      meningoencephalitis assessed at the time of the SPECT study with the Hunt and
      Hess scale, with separately recorded focal clinical signs, and with the Glasgow
      outcome scale (GOS) after 3 weeks. RESULTS: Count density values were
      significantly reduced in patients with bacterial meningoencephalitis as compared
      with the control subjects. Inhomogeneous tracer accumulation assessed by
      asymmetry indexes was significantly greater in patients than in the control
      group. With increasing Hunt and Hess scores, the count density values decreased
      and the asymmetry indexes increased. Patients with a poor outcome (GOS 1 to 3)
      had significantly higher asymmetry indexes and lower CDV values than did patients
      with a good outcome. CONCLUSION: Global and focal alterations of cerebral
      perfusion are frequent in bacterial and viral meningoencephalitis and correlate
      with acute clinical state.

PMID- 9541295
TI  - Hypophysitis: endocrinologic and dynamic MR findings.
AB  - PURPOSE: Our purpose was to assess the worth of dynamic MR imaging in the
      evaluation of vascular changes of the pituitary in patients with lymphocytic
      hypophysitis. METHODS: Five patients (four males, one female; 9 to 53 years old)
      with lymphocytic hypophysitis or infundibuloneurohypophysitis were studied. All
      patients underwent endocrinologic studies and a series of two to five MR
      examinations performed over a period of 8 months to 5 years, including a total of
      nine dynamic imaging studies. RESULTS: Two patients had panhypopituitarism and
      three had partial hypopituitarism. Diabetes insipidus was present in four
      patients. Among the five patients, the pituitary was enlarged in three, of whom
      two showed improvement on follow-up MR studies. Three patients had a thickened
      stalk, which improved on subsequent examinations. In all nine dynamic studies,
      the enhancement time of the whole pituitary was delayed to over 90 seconds, even
      though five of the nine conventional, simultaneously performed MR studies showed
      a normal pituitary. The peak time of posterior pituitary enhancement in the first
      dynamic study was also delayed in all patients (from 60 to 120 seconds). In two
      patients, normal early enhancement of the posterior pituitary was identified on
      initial studies but not on subsequent studies. CONCLUSION: Dynamic MR imaging can
      display an abnormality of the hypophysial vasculature even if the pituitary
      disease is seen to regress on the conventional MR study. The delay or even the
      lack of early enhancement of the posterior pituitary in lymphocytic hypophysitis
      may be due to secondary inflammatory changes.

PMID- 9541296
TI  - Rasmussen encephalitis: complementary role of multitechnique neuroimaging.
AB  - Rasmussen encephalitis is a chronic, progressive inflammation of the brain of
      unknown origin. Early diagnosis and treatment with immunoactive agents and/or
      hemispherectomy are sought to prevent the progressive cognitive decline that
      accompanies this disease. Combined anatomic and functional neuroimaging may serve
      to focus the diagnostic workup and to hasten brain biopsy for definitive
      diagnosis. Two biopsy proved cases of Rasmussen encephalitis are presented. The
      importance of MR imaging, single-photon emission computed tomography, and proton
      MR spectroscopy in the workup of this disease is discussed.

PMID- 9541297
TI  - Idiopathic hypertrophic cranial pachymeningitis with accumulation of thallium-201
      on single-photon emission CT.
AB  - We report a case of idiopathic hypertrophic cranial pachymeningitis in which a
      high accumulation of thallium-201 was observed on an early single-photon emission
      CT (SPECT) scan. The patient's symptoms initially improved with steroid therapy
      but recurred repeatedly. MR images failed to show any change with treatment;
      however, thallium-201 uptake correlated closely with the fluctuation of symptoms.
      201Tl-SPECT was therefore useful in identifying inflammatory activity that was
      not detected by MR imaging.

PMID- 9541298
TI  - The role of 99m-Tc HMPAO SPECT in the diagnosis of Creutzfeldt-Jacob disease.
AB  - A patient with acute dementia underwent imaging of the brain with technetium-99m
      hexamethylpropyleneamine oxime single-photon emission computed tomography.
      Regional perfusion abnormalities were identified in multiple locations,
      particularly in the left frontal lobe. This information was used to direct an
      open brain biopsy, which led to a diagnosis of Creutzfeldt-Jacob disease.

PMID- 9541299
TI  - Loss of digitations of the hippocampal head on high-resolution fast spin-echo MR:
      a sign of mesial temporal sclerosis.
AB  - PURPOSE: The purpose of our study was to determine the significance of the loss
      of visualization of digitations in the hippocampal head on high-resolution fast
      spin-echo MR images in the diagnosis of mesial temporal sclerosis (MTS). METHODS:
      MR examinations of 193 patients with intractable epilepsy were evaluated
      retrospectively for atrophy and/or T2 signal changes of the hippocampi. On the
      basis of these two criteria, MTS was diagnosed in 63 hippocampi. Twenty-four
      patients had surgery, and MTS was confirmed in all cases. A control group
      included 60 hippocampi in patients with frontal seizures but no MR-detectable
      abnormalities. In a second step, visibility of digitations in the hippocampal
      head was evaluated in the two groups of subjects. RESULTS: In the group of 63
      hippocampi in which MTS was diagnosed, digitations were not visible in 51 cases,
      poorly visible in eight, and sharply visible in four. Twenty-two of 24 hippocampi
      in which MTS was confirmed histologically had no MR-visible digitations. In the
      control group, digitations were sharply visible in 55 cases and poorly visible in
      five. Statistical analysis showed a significant difference in the visualization
      of digitations between hippocampi with MTS and those in the control group.
      CONCLUSION: With a sensitivity of 92% and a specificity of 100%, the finding of
      complete loss of digitations in the hippocampal head may be used as a major
      diagnostic criterion to establish the MR diagnosis of MTS. This morphologic sign
      may also be useful in the diagnosis of bilateral MTS or to validate the MR
      diagnosis of MTS when there is no obvious atrophy or changes in signal intensity.

PMID- 9541300
TI  - MR of hippocampal sclerosis: comparison of qualitative and quantitative
      assessments.
AB  - PURPOSE: Our goal was to compare the diagnostic accuracy of subjective visual
      assessment versus MR volumetry in evaluating hippocampal sclerosis and to
      determine whether MR volumetry is needed in the lateralization of this disease
      process. METHODS: MR imaging findings were studied retrospectively in 48 patients
      who underwent surgery for temporal lobe epilepsy and were compared with findings
      at MR volumetry on an Allegro workstation. Both visual assessment and volumetry
      were carried out in a blinded fashion with oblique coronal T1-weighted three
      dimensional MP-RAGE images obtained on either 1.0-T or 1.5-T units. Normal right
      left volumetric differences were recorded in 30 control subjects. The optimum
      cutoff threshold value for right-left volumetric differences in the sensitivity
      and specificity of volumetric measurement was obtained from receiver operating
      characteristic analysis. RESULTS: Sensitivity, specificity, positive and negative
      predictive values, and accuracy of visual assessment were 86%, 83%, 86%, 83%, and
      85%, respectively. For MR volumetry, with the optimum cutoff threshold value of
      right-left difference at 0.3 cm3, sensitivity, specificity, positive and negative
      predictive values, and accuracy were 81%, 82%, 87%, 83%, and 85%, respectively.
      CONCLUSION: Visual assessment was slightly superior to or similar to MR volumetry
      in assessing unilateral hippocampal sclerosis. MR volumetry of the hippocampus
      may not be needed for the evaluation of most cases of suspected hippocampal
      sclerosis.

PMID- 9541301
TI  - Familial arteriopathic leukoencephalopathy: imaging and neuropathologic findings.
AB  - We present the clinical, imaging, and neuropathologic data for a family with an
      autosomal dominant, nonhypertensive, progressive cerebral arteriopathy and
      leukoencephalopathy. Clinical presentation was characterized by progressive
      dementia, gait abnormalities, and, in some, Parkinson-like symptoms. MR
      abnormalities, consisting of white matter T2 hyperintensities and cystic
      appearing T1 hypointensities, were present in seven family members. The basal
      ganglia also showed cystic abnormalities. Neuropathologic examination in two
      cases revealed numerous lacunar infarctlike lesions, extensive demyelination, and
      widespread hyalinization of arteriolar walls with karyolysis and granular
      deposits within the media. These findings appear to constitute further evidence
      of a genetically determined arteriopathic leukoencephalopathy.

PMID- 9541302
TI  - MR of hereditary hemorrhagic telangiectasia: prevalence and spectrum of
      cerebrovascular malformations.
AB  - PURPOSE: Our goal was to describe the prevalence and types of cerebral vascular
      malformations (CVMs) seen with MR imaging in patients with hereditary hemorrhagic
      telangiectasia (HHT). METHODS: We reviewed retrospectively the brain MR images of
      184 consecutive patients with HHT. Catheter angiography was performed in 17
      patients with CVMs detected on MR images. RESULTS: MR imaging revealed 63 CVMs in
      42 patients. Classic arteriovenous malformations (n = 10) had a conspicuous
      network of vessels with flow voids and enlarged adjacent pial vessels. Apparent
      venous malformations (n = 5) were best seen after administration of contrast
      material as a prominent vessel coursing through normal brain parenchyma.
      Indeterminate vascular malformations (n = 48) had a spectrum of appearances
      characterized by variable combinations of heterogeneous signal intensity,
      enhancement, or hemosiderin. Angiography in 17 patients revealed 47 CVMs. Forty
      six were arteriovenous malformations (AVMs), including 25 CVMs not seen with MR
      imaging and 21 CVMs that by MR criteria included 8 AVMs and 13 indeterminate
      vascular malformations. Angiography confirmed 1 venous malformation seen with MR
      imaging but failed to detect 3 indeterminate lesions revealed by MR imaging.
      CONCLUSION: MR imaging of a large cohort of consecutive patients with HHT
      revealed a CVM prevalence of 23% (42/184). Most CVMs (48/63) have an atypical
      appearance for vascular malformations on MR images. Angiographic correlation
      suggests that MR imaging underestimates the prevalence of CVMs and that the
      majority of indeterminate CVMs, despite their variable MR appearance, are AVMs.

PMID- 9541303
TI  - Acquired hepatocerebral degeneration: MR and pathologic findings.
AB  - Acquired (non-Wilsonian) hepatocerebral degeneration (AHD) is a rare irreversible
      neurologic syndrome that occurs in patients with chronic liver disease associated
      with multiple metabolic insults. The pathophysiology and the locations of the
      cerebral injuries are incompletely understood. We describe a patient with fatal
      hepatic cirrhosis and AHD in whom MR images showed abnormalities in the brachium
      pontis bilaterally. Neuropathologic evaluation disclosed multiple regions of
      subcortical spongiform white matter changes.

PMID- 9541304
TI  - Isolated cortical venous thrombosis and ulcerative colitis.
AB  - Aseptic cortical venous thrombosis is rare without concomitant dural sinus
      thrombosis. Ulcerative colitis is associated with both dural sinus thrombosis and
      isolated cortical venous thrombosis. We describe a 26-year-old woman with
      ulcerative colitis who had a spontaneous cerebral hemorrhage. An overlying
      thrombosed cortical vein was identified on spin-echo MR images and confirmed with
      angiography. Signal characteristics of thrombosed cortical veins are similar to
      those described in dural sinus thrombosis.

PMID- 9541305
TI  - T2-weighted three-dimensional fast spin-echo MR in inflammatory peripheral facial
      nerve palsy.
AB  - PURPOSE: Our objective was to identify histologically and intraoperatively
      verified focal nerve thickening of the distal intrameatal segment on three
      dimensional fast spin-echo (FSE) T2-weighted MR images as a new diagnostic
      criterion in patients with inflammatory peripheral facial nerve palsy. METHODS:
      Twenty-two patients with clinically diagnosed unilateral (n = 20) or bilateral (n
      = 2) inflammatory peripheral facial nerve palsy were examined on a 1.5-T MR
      imager using noncontrast and contrast-enhanced T1-weighted SE sequences and 3-D
      T2-weighted FSE sequences with secondary reformations. Abnormal contrast
      enhancement and possible focal nerve thickening of the distal intrameatal
      segment, labyrinthine nerve segment, and geniculate ganglion region were analyzed
      prospectively. RESULTS: In all patients, the T1-weighted postcontrast SE images
      showed characteristic smooth, linear, abnormally intense contrast enhancement of
      the distal intrameatal segment, indicating peripheral inflammatory nerve palsy.
      In 23 nerves (96%) a focal bulbous nerve thickening of the distal intrameatal
      segment was observed on 3-D T2-weighted FSE images. In 100% of patients with
      peripheral inflammatory facial nerve palsy, postcontrast T1-weighted SE images
      showed a smooth, linear, and abnormally intense contrast enhancement of the
      distal intrameatal segment; reformatted very thin 3-D T2-weighted FSE images
      showed a focal bulbous nerve thickening of the distal intrameatal segment in 96%
      of patients. These findings corresponded to intraoperative and histologic
      findings. CONCLUSION: Three-dimensional T2-weighted FSE sequences are fast and
      cheap compared with T1-weighted postcontrast images, but secondary reformations
      are time-consuming and require exact anatomic knowledge for careful analysis of
      the different nerve segments.

PMID- 9541306
TI  - An early MR observation of carotid involvement by retropharyngeal abscess.
AB  - We report early carotid involvement by retropharyngeal abscess in a 4-year-old
      boy. MR imaging showed enhancement of the wall and narrowing of the lumen of the
      internal carotid artery, which were thought to reflect spasm and/or arteritis.
      Prompt treatment may have prevented hemorrhagic and neurologic complications.

PMID- 9541307
TI  - Pseudoaneurysm of the petrous internal carotid artery after skull base infection
      and prevertebral abscess drainage.
AB  - A 37-year-old woman with a skull base infection sustained massive oropharyngeal
      bleeding after incisional nasopharyngeal biopsy and drainage of a prevertebral
      abscess. A pseudoaneurysm originating at the petrous portion of the internal
      carotid artery was initially misinterpreted on MR images as typical postoperative
      change within a resolving abscess cavity. Follow-up MR imaging and conventional
      angiography ultimately disclosed the pseudoaneurysm.

PMID- 9541308
TI  - Head and neck lipomas: sonographic appearance.
AB  - PURPOSE: The diagnosis of cervical lipoma may not always be clinically apparent,
      in which case patients are frequently referred for sonography. The purpose of
      this study was to document the sonographic features of head and neck lipomas.
      METHODS: Twenty-five patients with soft-tissue masses in the neck had sonography
      as their initial imaging study. A lipoma was suspected on the basis of findings
      at clinical examination in only eight of these patients. Lipoma was confirmed by
      fine-needle aspiration cytology in 11 patients, by excision biopsy in five
      patients, by CT in two patients, and by clinical examination with clinical
      sonographic follow-up (6 months to 2 years) in seven cases. RESULTS: Lipomas were
      well-defined (88%), compressible (100%), elliptical masses with the longest
      diameter parallel to the skin surface. All contained multiple echogenic lines
      parallel to the skin surface with no evidence of posterior enhancement or
      attenuation and no flow on color Doppler sonography. Compared with adjacent
      muscle, 76% of all lipomas were hyperechoic, 8% isoechoic, and 16% hypoechoic.
      CONCLUSION: The characteristic sonographic appearance of head and neck lipomas is
      that of an elliptical mass parallel to the skin surface that is hyperechoic
      relative to adjacent muscle and that contains linear echogenic lines at right
      angles to the ultrasound beam.

PMID- 9541309
TI  - Papillary thyroid carcinoma: MR diagnosis of lymph node metastasis.
AB  - PURPOSE: The purpose of this study was to ascertain the usefulness of MR imaging
      in the diagnosis of nodal metastasis of papillary thyroid carcinoma and to
      establish the most indicative MR criteria of metastasis. METHODS: Pathologic
      records and MR images in 50 patients with papillary thyroid carcinoma were
      reviewed. Each neck was divided into four nodal levels, so that 200 nodal levels
      were assessed in all. The maximum of the minimum transverse diameters of the
      lymph nodes on each nodal level measured on MR images and the certainty of
      metastasis as determined by a head and neck radiologist on the basis of
      morphologic aspects were compared with the pathologic findings by using receiver
      operating characteristic curves. The presence or absence of cystic nodes on each
      nodal level was also evaluated. RESULTS: Metastasis was found on 87 (44%) of the
      nodal levels in 34 (68%) of the patients. A cystic node was identified on 33
      (17%) of the nodal levels in 13 (26%) of the patients and was seen only on
      positive nodal levels. Morphologic diagnosis by the radiologist was better than
      that obtained by measurement. With the combined criteria of a cystic node or a
      node of 13 mm or more for the maximum of the minimum transverse diameters,
      specificity was 100% with an 82% accuracy and always indicated metastasis (100%
      positive predictive value). However, 41% of the metastatic nodes were missed with
      this criterion (59% sensitivity). CONCLUSION: MR imaging was useful for
      diagnosing metastatic nodes; a nodal diameter threshold of 13 mm or the presence
      of a cystic node strongly indicated metastasis from papillary thyroid carcinoma.

PMID- 9541310
TI  - MR of denervated tongue: temporal changes after radical neck dissection.
AB  - PURPOSE: The purpose of this study was to evaluate the temporal changes of MR
      imaging in the denervated tongue after a radical neck dissection. METHODS: One
      hundred seventy-four consecutive MR studies in 116 patients with radical neck
      dissections for malignant tumors of the head and neck were evaluated
      retrospectively. Patients with tumors involving the tongue or hypoglossal nerve
      were not included in this study. RESULTS: Abnormal signal intensity and/or
      hemiatrophy on the side of the tongue operated on was seen in 22 patients who had
      hypoglossal paralysis after radical neck dissection. The denervated side of the
      tongue appeared hypointense to hyperintense relative to the normal side on T1
      weighted images and hyperintense on T2-weighted images. Signal intensity ratios
      of the abnormal to normal muscles were 0.9-1.6 on T1-weighted images and 1.3-2.8
      on T2-weighted images. High signal intensity on T1-weighted images appeared 5
      months or more after the dissection, whereas on T2-weighted images, the most
      prominent increases in signal intensity appeared in the first several months
      after denervation. Hemiatrophy of the tongue was observed on MR images obtained
      more than 6 months after surgery. CONCLUSION: MR findings in the denervated
      tongue are compatible with histologic changes and are characterized by an
      enlarged extracellular fluid space or fatty infiltration. The pattern of signal
      intensity and the degree of hemiatrophy suggest the duration of denervation.

PMID- 9541311
TI  - Mandibular erosion from silastic implants: evaluation with a dental CT software
      program.
AB  - Silastic implants used to augment the chin during cosmetic surgery may cause
      erosive bone changes and complications. We describe the radiologic appearance of
      these changes and the dental CT reformatting programs by which they may be
      assessed. Multiplanar CT scans of four patients with Silastic chin implants were
      evaluated retrospectively for implant density, presence and size of bone defects,
      relationship of defects to root apices, relationship of defects to mental
      foramen, and associated findings. The dental CT software program was instrumental
      in delineating the relationship between the bone defects and the root apices.

PMID- 9541312
TI  - Imaging patterns of neonatal hypoglycemia.
AB  - PURPOSE: Our purpose was to report the patterns of injury observed in five
      patients who suffered brain damage consequent to neonatal hypoglycemia. METHODS:
      The imaging studies and clinical records of five patients with brain damage
      caused by neonatal hypoglycemia were reviewed retrospectively. Patterns of injury
      were compared with those described in the literature and those seen in neonatal
      hypoxic-ischemic injury. RESULTS: Diffuse cortical and subcortical white matter
      damage was seen, with the parietal and occipital lobes affected most severely.
      Globus pallidus injury was present in one patient who had the most severe
      cortical injury. CONCLUSION: We found a specific pattern of injury that
      correlates well with the sparse pathologic and imaging reports on neonatal
      hypoglycemia. We speculate that the patterns of damage are the result of regional
      hypoperfusion and excitatory toxicity with cell-type-specific injury.

PMID- 9541313
TI  - Efficacy of fast screening MR in children and adolescents with suspected
      intracranial tumors.
AB  - PURPOSE: Our purpose was to determine the sensitivity, specificity, and receiver
      operator characteristic (ROC) curve of a fast screening MR protocol in children
      and adolescents with suspected intracranial tumors. METHODS: One hundred forty
      one patients (mean age, 9.7 years; range, 2 months to 23.5 years) with suspected
      brain tumor were entered in a case-control study. Eighty-seven patients had
      intracranial tumors (31 suprasellar/hypothalamic, 27 supratentorial, 26
      infratentorial, and three pineal) and 54 patients in the control group had other
      disorders. Two neuroradiologists reviewed blindly a detailed three-sequence
      conventional protocol (acquisition time, 8 minutes 27 seconds) and a two-sequence
      fast screening MR protocol (acquisition time, 4 minutes 44 seconds). RESULTS:
      Sensitivity and specificity of the fast screening protocol for intracranial
      tumors was 100% and 92.6%, respectively. The areas under the ROC curves were
      0.966 for the fast screening and 0.980 for the conventional MR protocol. No
      diagnostic performance difference was found between the ROC curves using the Az
      index. A kappa statistic of .93 for both examinations indicated excellent
      interobserver agreement. Additional MR sequences and other neuroimaging studies
      were not deemed necessary to exclude the presence of an intracranial tumor.
      CONCLUSION: A fast dual-plane brain MR protocol may be adequate to screen
      children and adolescents thought to have an intracranial tumor. The less than 5
      minute acquisition time allows a complete examination (including preparation) to
      be performed in 10 to 15 minutes. Future studies are recommended before this time
      efficient neuroimaging examination is incorporated into clinical practice.

PMID- 9541314
TI  - Proton MR spectroscopic characteristics of pediatric pilocytic astrocytomas.
AB  - PURPOSE: We report the common characteristics of juvenile pilocytic astrocytomas
      revealed by proton MR spectroscopy. METHODS: Eight children with pilocytic
      astrocytomas were studied with proton MR spectroscopy. The selected sampling
      volume was approximately 4 cm3, obtained from solid tumor. To localize the
      sampling volume, we used point-resolved spectroscopy (PRESS) and stimulated-echo
      acquisition mode (STEAM) techniques to acquire long- and short-TE spectra,
      respectively. Spectra from PRESS and STEAM sequences were processed using
      Lorentzian-to-Gaussian transformation and exponential apodization, respectively.
      For PRESS (2000/270) spectra, peaks of creatine, choline, N-acetylaspartate
      (NAA), and lactate resonances were integrated; for STEAM (2000/20) spectra, we
      measured the amplitude of the peaks at 3.2, 2.0, 1.3 and 0.9 ppm. RESULTS: An
      elevated lactate doublet was observed in the PRESS spectra. The choline/NAA ratio
      was 3.40. The amplitude ratios of the lipid pattern (0.9, 1.3 and 2.0 ppm) to
      choline were all below one. CONCLUSION: Despite the benign histology of the
      tumor, which generally lacks necrosis, a lactate signal was detected in all eight
      patients studied. A dominant lipid pattern was not observed.

PMID- 9541315
TI  - Usefulness of contrast material in MR of patients with neurofibromatosis type 1.
AB  - PURPOSE: Our objective was to determine the usefulness of routine administration
      of contrast material in brain MR imaging for the evaluation of areas of probable
      myelin vacuolization and neoplasms in patients with neurofibromatosis type 1 (NF
      1). METHODS: We retrospectively reviewed 112 consecutive contrast-enhanced brain
      MR studies obtained over a period of 7 years in 109 symptomatic and asymptomatic
      patients compiled from two institutional NF-1 data bases. MR studies were
      analyzed for areas of probable myelin vacuolization, with attention to degree of
      enhancement and its impact on lesion detection and characterization. Usefulness
      of contrast material was graded as 0 = not useful, 1+ = somewhat useful, and 2+ =
      useful. RESULTS: Of 112 studies, 45% (n = 49) were normal. In the remaining 63
      studies, 88 regions of probable myelin vacuolization and 52 tumors were
      identified. Enhancement was not observed in any regions of probable myelin
      vacuolization. Enhancement was present in 31% of tumors, and, of these, was found
      to be useful in 44%, somewhat useful in 12%, and not useful in 44%. For enhancing
      tumors, contrast agent was useful for lesion detection in 19% and for lesion
      characterization in 25%. CONCLUSION: Contrast administration is useful in
      baseline MR studies to maximize tumor detection and characterization, to add
      confidence to the diagnosis of benign probable myelin vacuolization, and to
      document stability of neoplasms on follow-up examinations.

PMID- 9541316
TI  - Rhombencephalosynapsis: cerebellar embryogenesis.
AB  - We describe two infants in whom rhombencephalosynapsis was diagnosed with MR
      imaging in vivo. In contrast to Dandy-Walker malformation, the vermian
      maldevelopment in this anomaly is characterized by an absence of the anterior
      vermis and a deficiency of the posterior vermis. The cerebellar hemispheres are
      fused. In an attempt to identify the pathogenesis of these anatomic
      manifestations, we question the traditional concept of the embryologic
      development of the cerebellar primordium.

PMID- 9541317
TI  - MR findings of Werdnig-Hoffmann disease in two infants.
AB  - We report two infants with Werdnig-Hoffmann disease diagnosed by means of spinal
      MR imaging, histopathologic examination of muscle biopsy specimens, cloned DNA
      analysis, electrophysiological examination, and clinical history. The MR findings
      were consistent with previous histopathologic reports.

PMID- 9541318
TI  - Frequency of cerebral vasospasm in patients treated with endovascular occlusion
      of intracranial aneurysms.
AB  - The purpose of this study was to retrospectively compare a group of 19 patients
      treated with craniotomy and aneurysmal clipping with a group of 18 patients who
      were treated via endovascular occlusion with Guglielmi detachable coils in regard
      to frequency and severity of cerebral vasospasm. METHODS: All patients were
      treated within 48 hours of ictus. In the endovascular group, nine patients had
      Hunt and Hess grade I subarachnoid hemorrhage, five patients had grade II
      aneurysms, and four patients had grade III. According to the Fisher
      classification, one aneurysm was grade I, nine were grade II, and eight were
      grade III. Twelve of the aneurysms were on the anterior circulation and seven
      were on the posterior circulation. In the surgical group, 10 patients had Hunt
      and Hess grade I hemorrhage, seven had grade II aneurysms, and two had grade III.
      Nine of these were Fisher grade II and 10 were grade III. Eighteen aneurysms were
      on the anterior circulation and one was on the posterior circulation.
      Endovascularly treated patients were medically treated identically to those in
      the surgical group, with prophylactic volume expansion and hemodilution
      immediately after endovascular occlusion, except that they also received 48 hours
      of full heparinization followed by 24 hours of dextran infusion after
      endovascular occlusion. RESULTS: All four patients in the endovascular group in
      whom delayed neurologic deficits developed as a result of vasospasm responded to
      elevation of blood pressure and did not require either mechanical or chemical
      angioplasty to reverse their symptomatology. In the surgical group, 14 of 19
      developed clinical vasospasm, with elevation of their transcranial Doppler
      velocities, and required maximum triple-H (hypertensive, hypervolemic,
      hemodilutional) therapy. Three of these patients required mechanical and
      pharmacologic angioplasty. No surgical complications were incurred as a direct
      result of the craniotomy. One patient in the endovascular group developed a
      femoral pseudoaneurysm as a complication of the procedure and postocclusion
      anticoagulation. No thromboembolic events were noted in this group. CONCLUSION:
      In patients with similar Hunt and Hess grades and Fisher grades, preliminary data
      suggest that the frequency and severity of cerebral vasospasm may be reduced in
      those treated by endovascular occlusion of their aneurysm as compared with those
      treated by direct surgical clipping.

PMID- 9541319
TI  - Endovascular therapy of idiopathic cavernous aneurysms over 11 years.
AB  - PURPOSE: We report our experience with 42 patients with 48 cavernous carotid
      aneurysms, of whom 32 were treated with endovascular techniques and 10 were
      managed conservatively. METHODS: The 48 aneurysms were divided into two subgroups
      by location: 23 were at the C-3 portion of the carotid artery (small, saccular
      aneurysms with an epidural, partly intracavernous location) and 25 originated at
      the C4-5 segment (large or giant often fusiform aneurysms with a true
      intracavernous location). Morphologic features in both groups correlated well
      with differences in clinical presentation and also influenced therapy. Sixteen of
      the 25 C4-5 aneurysms (all large or giant) were treated by balloon occlusion of
      the parent artery, four (with narrow necks) were treated with Guglielmi
      detachable coils (GDCs), and five were not treated (asymptomatic or minimally
      symptomatic). Twelve of 13 C-3 aneurysms were treated with GDCs. Ten C-3
      aneurysms were not treated. RESULTS: Ophthalmoplegia resolved or improved in nine
      of 12 patients treated with parent artery occlusion. All aneurysms treated by
      carotid occlusion thrombosed. Twelve of the 17 aneurysms treated with GDCs were
      100% filled by the coils, four were 80% to 95% filled, and one was only 40%
      filled. Seven of the 100% filled aneurysms remained completely occluded, two
      showed slight coil compaction, and in three, follow-up angiography was not
      available. Among the incompletely filled aneurysms, two remained unchanged, one
      showed progressive thrombosis, a fourth revealed coil compaction, and in one,
      follow-up angiography was not available. One thromboembolic stroke and three
      transient ischemic attacks occurred perioperatively, for a permanent morbidity of
      3.5% and a transient morbidity of 9%. There was no mortality. Mean clinical
      follow-up was 33 months; mean angiographic follow-up of patients treated with
      GDCs was 11 months. CONCLUSION: Surgically difficult cavernous aneurysms can be
      obliterated by embolization with excellent clinical results. Detachable coils
      have become an important endovascular tool, especially for narrow-necked
      cavernous aneurysms of the C-3 segment, which can be protected against rupture in
      the subarachnoid space in most cases.

PMID- 9541320
TI  - Embolization of experimentally created aneurysms with a laser-activated
      detachable coil device.
AB  - Our experimental study in dogs suggests that laser-activated detachable coil
      devices show promise in the embolization of carotid aneurysms, allowing the
      interventionalist greater control than possible with nonretractable coil systems
      and permitting detachment of the coil from the wire in seconds.

PMID- 9541321
TI  - Transvenous embolization as the primary therapy for arteriovenous fistulas of the
      lateral and sigmoid sinuses.
AB  - PURPOSE: We report on the evolution in one institution from transarterial
      embolization for the treatment of dural arteriovenous fistulas of the lateral and
      sigmoid sinuses to the safer and more durable technique of transvenous
      endovascular therapy for the majority of these lesions. METHODS: Arterial,
      venous, and combined embolizations were performed for 24 fistulas of the lateral
      and sigmoid sinuses between August 1991 and December 1996. The patients were
      followed up clinically for 2 to 63 months, with a mean follow-up period of 30
      months. RESULTS: Nine patients had arterial embolization without transvenous
      treatment: five of the nine had angiographic and clinical obliteration of their
      fistulas; two of the nine, with unusual lesions, required surgery; and the
      remaining two had recurrences and were not retreated. Seven patients had both
      arterial embolization and coil embolization (packing) of the dural sinuses, four
      after arterial embolization had failed to cure the lesions; in all seven, the
      fistulas were obliterated angiographically and clinically. Eight patients had
      only transvenous coil embolization of the dural sinuses; all eight were cured.
      One patient had minimal arterial embolization during the primary venous
      embolization procedure. Complications occurred in two patients, both related to
      arterial embolization with ethanol. CONCLUSION: Our experience suggests that
      arterial embolization of dural arteriovenous fistulas of the lateral and sigmoid
      sinuses is associated with a low cure rate and high rate of recurrence, whereas
      transvenous endovascular packing of the involved segment of the sinus results in
      a high cure rate that obviates arterial embolization or surgical excision in most
      cases.

PMID- 9541322
TI  - Predicting hemodynamic ischemia by transcranial Doppler monitoring during
      therapeutic balloon occlusion of the internal carotid artery.
AB  - PURPOSE: Our objective was to evaluate the sensitivity of transcranial Doppler
      (TCD) sonographic monitoring during permanent balloon occlusion of the internal
      carotid artery (ICA) in predicting hemodynamic ischemia. METHODS: Thirty-two
      consecutive patients underwent controlled therapeutic balloon occlusion of the
      ICA. Selection criteria included assessment of the circle of Willis by
      compression angiography, clinical tolerance during a 20-minute test occlusion,
      and TCD monitoring of the ipsilateral middle cerebral artery. The mean blood flow
      velocity (MBFV) (n = 32) and pulsatility index (PI) (n = 28) were recorded. In 25
      patients, MBFV changes upon motor stimulation were recorded before and after ICA
      occlusion. RESULTS: Twenty-eight (88%) of the patients had no complications.
      Three patients suffered delayed symptoms 30 minutes to 20 hours after balloon
      detachment. Two of these patients recovered spontaneously within 1 day, the other
      improved after extracranial/intracranial (EC/IC) bypass surgery. One patient, who
      did not tolerate the test occlusion, suffered a hemodynamic stroke despite EC/IC
      bypass before permanent balloon occlusion. No embolic complications occurred. The
      mean MBFV reduction was 20% (range, 0% to 55%); the mean PI reduction was 20%
      (range, 0% to 56%). No complications occurred in patients who had mild MBFV and
      PI reduction (30% or less, n = 21). All three patients with severe MBFV or PI
      reduction (> 50%) had neurologic symptoms. Among those with moderate MBFV or PI
      reduction (30% to 50%, n = 8), symptoms developed in only one patient who had
      moderate reduction of both MBFV (33%) and PI (38%). Motor vasoreactivity showed
      wide variation and was markedly reduced in two symptomatic patients. CONCLUSION:
      TCD monitoring reflects changes in cerebral hemodynamics after therapeutic
      balloon occlusion of the ICA. MBFV and PI reductions under 30% are highly
      predictive of clinical tolerance. A reduction of more than 50% may be a critical
      threshold for the occurrence of symptoms; in such cases, EC/IC bypass should be
      considered before proceeding with permanent balloon occlusion.

PMID- 9541323
TI  - Craniocervical dural fistula associated with cervical myelopathy: angiographic
      demonstration of normal venous drainage of the thoracolumbar cord does not rule
      out diagnosis.
AB  - We report a case of craniocervical dural arteriovenous fistula with perimedullary
      venous drainage associated with cervical myelopathy in which spinal angiography
      showed a normal venous phase after injection of the artery of Adamkiewicz. We
      conclude that because of the complex venous drainage of the spinal cord, a dural
      arteriovenous fistula with spinal drainage cannot be ruled out solely because a
      normal venous phase is seen in the lower part of the cord, as has previously been
      suggested.

PMID- 9541324
TI  - Pericoccygeal hidrocystoma.
AB  - We report the imaging findings of pericoccygeal hidrocystoma in a 52-year-old
      woman. Sonography showed a large cystic lesion with internal echoes in the
      pericoccygeal region; it appeared as a well-defined, low-density mass on CT, and
      as a high-signal-intensity mass on T1- and T2-weighted MR images. Histopathologic
      examination revealed an apocrine hidrocystoma.

PMID- 9541325
TI  - Proton MR spectroscopy and the ring-enhancing lesion.

PMID- 9541326
TI  - What's your favorite PET story?

PMID- 9541327
TI  - The reversible posterior cerebral edema syndrome.

PMID- 9541328
TI  - Does reduction in vascular trauma during treatment of acutely ruptured saccular
      aneurysms reduce the incidence of vasospasm?

PMID- 9541329
TI  - Neonatal hypoglycemia: unraveling a mystery.

PMID- 9541330
TI  - Scanning electron microscopic study of the migrated platinum coil after
      endovascular embolization of a giant cerebral aneurysm.

PMID- 9541332
TI  - Clozapine reduces violence and persistent aggression in schizophrenia.
AB  - Violence and persistent aggression are serious problems in the general population
      and among certain psychiatric patients. Violence and persistent aggression have
      been associated with suicidal ideation and substance abuse, characteristics of
      chronically ill, and in many instances, treatment-resistant schizophrenia
      individuals. Assessment of dangerousness in psychiatric patients involves
      evaluation of sociodemographic and clinical factors. A substantial number of
      neurologic and psychiatric disorders are associated with pathologic anger and
      aggression; of these, the association between schizophrenia and
      violence/aggression is the best described. Neurotransmitters that have been
      implicated in aggressive and violent behavior include serotonin, norepinephrine,
      and dopamine. Current pharmacotherapy of pathologic aggression involves the use
      of multiple agents on a trial-and-error basis, with varying degrees of response.
      Unfortunately, this approach subjects patients to numerous side effects,
      including the extrapyramidal symptoms associated with the use of conventional
      antipsychotics. This paper will review evidence for the efficacy of clozapine in
      the treatment of aggression and violence in the treatment-refractory patient. The
      reduction in violence and persistent aggression with clozapine treatment should
      improve the chances for integration of the schizophrenia patient into the
      community and provide cost savings to society.

PMID- 9541331
TI  - Reducing clozapine-related morbidity and mortality: 5 years of experience with
      the Clozaril National Registry.
AB  - The Clozaril National Registry (CNR) was created to help protect patients from
      developing potentially fatal agranulocytosis secondary to treatment with the
      antipsychotic medicine clozapine. The CNR, designed and maintained by the
      manufacturer of the branded Clozaril (clozapine), has the principal goals of (1)
      prophylaxis-preventing inappropriate retreatment, and (2) quality assurance
      overseeing adherence to a "no blood, no drug" policy. This article reviews the
      estimated impact of the CNR on clozapine-related morbidity and mortality over the
      first 5 years of commercial experience in the United States. METHOD: Complete
      data on leukopenia and agranulocytosis, gathered from the CNR database for the
      period of 1990-1994, were reviewed and compared with data from the pre-CNR
      period. RESULTS: Use of clozapine in 99,502 patients according to package
      labeling requirements (distribution of the medicine linked to mandated white
      blood cell count testing) was associated with a total of 382 cases of
      agranulocytosis (0.38%) versus an expected cumulative total of 995 cases (based
      on the pre-CNR rate of 1% to 2%). Based on the expected agranulocytosis rate, up
      to 149 deaths might have been anticipated. Instead, there were only 12 deaths
      attributed to complications of agranulocytosis. CONCLUSION: The CNR provides for
      universal rechallenge protection as well as controlled dispensing of clozapine.
      It also serves as an early warning system to promote the safe and effective use
      of clozapine. The CNR includes quality assurance mechanisms designed to enhance
      compliance. Despite the added logistic requirements this system places upon
      physician, pharmacist, and manufacturer, the CNR has helped to reduce
      substantially potential fatal outcomes. The CNR reinforces both patient and
      treatment system compliance. Based on this favorable experience concerning
      agranulocytosis and associated fatalities, the Neuropsychopharmacology Advisory
      Committee to the U.S. Food and Drug Administration has unanimously recommended a
      reduction in frequency of the white blood cell count testing requirement after 6
      months to every 14 days, instead of weekly. Finally, the CNR database containing
      white blood cell count and demographic data on every patient in the United States
      who has received the medicine has served as a unique epidemiologic database.

PMID- 9541333
TI  - Suicide in schizophrenia: risk factors and clozapine treatment.
AB  - Suicide is the major cause of premature death in patients with schizophrenia.
      Among these patients, 40% report suicidal thoughts, 20% to 40% make unsuccessful
      suicide attempts, and 9% to 13% end their lives by suicide. Traditional
      antipsychotic drugs undertreat many schizophrenic patients and can produce
      serious side effects, such as tardive dyskinesia. Clozapine is the only
      antipsychotic drug that has been shown in controlled clinical trials to be
      effective in reducing both positive and negative symptoms in schizophrenic
      patients who fail to respond to typical neuroleptic drugs. The potential decrease
      in suicide among schizophrenic patients treated with clozapine is estimated to be
      as high as 85%. Treatment with clozapine is cost-effective, and the significant
      decrease in the risk of suicide far outweighs the very low risk of mortality from
      agranulocytosis. Clozapine should be considered for treatment of both neuroleptic
      resistant and neuroleptic-responsive schizophrenic patients who have persistent
      suicidal thoughts or behavior.

PMID- 9541334
TI  - Facilitating compliance with antipsychotic medication.
AB  - Noncompliance with medication is common among patients who have schizophrenia and
      is a leading cause of rehospitalization in this population. Both standard and
      subjective risk-factor assessments have been used to identify patients who are
      likely to refuse or discontinue treatment. Noncompliant patients who have
      schizophrenia commonly have been treated with potent D2 dopamine-receptor
      antagonists and therefore may have experienced extrapyramidal side effects. The
      newer antipsychotics (i.e., serotonin-dopamine antagonists) are efficacious in
      reducing the symptoms of schizophrenia without associated dysphoria and motor
      side effects. Clozapine and other newer antipsychotics may improve certain
      aspects of cognition. The improved psychiatric state and cognitive function may
      facilitate "involved compliance" as a result of increased insight, awareness, and
      judgment. These cognitive faculties allow patients to appreciate their improved
      state and take steps to maintain it. The periodic visits for blood monitoring
      mandated for clozapine therapy also facilitate the formation of a therapeutic
      alliance that allows the clinician to monitor compliance. Facilitating involved
      compliance this way among patients who have schizophrenia may reduce the cost of
      this disorder to society.

PMID- 9541335
TI  - Substance abuse in schizophrenia: a review.
AB  - Approximately half of the patients who suffer from schizophrenia are also
      substance abusers at some time during their illness. The motivational drive
      toward abusive consumption is compounded in individuals with schizophrenia who
      turn toward substances with reinforcing properties to alleviate aspects of
      psychosis. This review examines the prevalence, etiology, and clinical effects of
      substance abuse (e.g., alcohol, nicotine, cocaine) among individuals with
      schizophrenia. Clearly, substance abuse persists despite and in spite of
      treatment with typical antipsychotics. The efficacy of newer generation
      antipsychotics in the reduction of substance abuse among the schizophrenic
      population has yet to be established, but clozapine has been shown to reduce
      alcohol, smoking, and cocaine use. Hence, clozapine is a therapeutic option for
      dually diagnosed patients because of its superior efficacy relative to
      conventional neuroleptics and its capacity to control substance abuse.

PMID- 9541336
TI  - Effects of clozapine therapy in schizophrenic individuals at risk for tardive
      dyskinesia.
AB  - Neuroleptics were the first modern class of pharmacotherapeutic agents available
      for the treatment of schizophrenia. Although they were effective in reducing
      florid psychotic symptoms, up to 90% of treated individuals subsequently
      developed extrapyramidal symptoms (EPS) (akathisia, dystonia, or parkinsonism),
      and about 20% developed tardive dyskinesia (TD). When clozapine became
      commercially available for treatment-resistant and treatment-intolerant (i.e.,
      prone to EPS and TD) schizophrenic individuals, it became apparent that an
      antipsychotic need not induce motor side effects to be efficacious in reducing
      the symptomatology of schizophrenia. Sociodemographic, behavioral, and clinical
      predictors of TD are useful in identifying a subset of schizophrenic individuals
      who would benefit from treatment with clozapine, the prototype atypical
      antipsychotic whose efficacy and motor side effect profile are superior to those
      of chlorpromazine. This favorable motor side effect profile of clozapine
      contributes to improved patient outcomes by reducing noncompliance, substance
      abuse, and suicide, resulting in improved quality of life and savings on health
      care costs.

PMID- 9541337
TI  - Maximizing clozapine therapy: managing side effects.
AB  - Since its introduction to the United States in 1990, the benefits of clozapine
      use have been repeatedly validated. Clozapine remains the only antipsychotic with
      proven efficacy in treatment-resistant schizophrenia. Because clozapine has been
      part of the psychiatric pharmacopeia for considerably less time than
      neuroleptics, which have dominated the field for over 4 decades, its
      underutilization may be partly attributed to a lack of experience in managing
      associated side effects. Most side effects associated with clozapine are typical
      of antipsychotics in general, and with clozapine, these side effects are
      typically benign, tolerable, and manageable. It is conceivable that there remains
      a concern over the risk of agranulocytosis. However, the mandatory blood
      monitoring carried out through the Clozaril National Registry has considerably
      reduced the incidence of fully developed cases of agranulocytosis from
      premarketing values of approximately 1% to 2% to current values of 0.38% and
      virtually prevented mortalities. These values are likely to decrease further with
      the application of cytokine augmentation therapy among patients developing blood
      dyscrasias. Many side effects of clozapine are observed early after treatment
      onset and are greatly reduced by dose adjustments. Appropriate management of side
      effects will facilitate a maximization of the benefits of clozapine treatment.
      Clearly, the benefits of clozapine therapy far outweigh its risks.

PMID- 9541338
TI  - Optimizing treatment with clozapine.
AB  - Clozapine is the only antipsychotic agent that is effective in treatment
      resistant schizophrenia. Despite its superior efficacy to chlorpromazine and the
      fact that it has fewer extrapyramidal side effects than conventional
      antipsychotics do, clozapine is relatively underused. This may be due in part to
      a lack of appreciation of clozapine's favorable risk-benefit ratio in many
      patients. In addition, clozapine is only indicated for use in patients who fail
      to respond adequately to standard antipsychotic treatment. Treatment with
      clozapine considerably improves psychiatric well-being and reduces readmission to
      the hospital and reduces family burden in many severely ill patients. However,
      clozapine is associated with severe side effects, including weight gain,
      tachycardia, sedation, seizures, and agranulocytosis. These risks must be weighed
      against the risks associated with schizophrenia (e.g., suicide). The death rate
      attributed to clozapine-induced agranulocytosis has been low, a fact that is
      largely attributable to safety measures such as the Clozaril National Registry.
      Determining the optimal dosage for each patient will maximize the benefits of
      treatment while reducing side effects. In some patients, monitoring plasma levels
      of drug may aid in optimizing treatment. The optimal plasma level of clozapine is
      200 to 350 ng/mL. This usually corresponds to a daily dose of 200 to 400 mg,
      although dosage must be individualized. If patients improve significantly during
      treatment with clozapine, they should continue to be treated with clozapine and
      should be withdrawn from this treatment only when medically warranted. Psychotic
      relapse rates may be as high as 80% among patients switched from clozapine to
      other novel antipsychotic agents.

PMID- 9541339
TI  - Periodontal disease associated with interdental osteotomies after orthognathic
      surgery.
AB  - PURPOSE: One of the main reasons for orthodontics and orthognathic surgery is the
      prevention of dental loss caused by periodontal disease. Until now there have
      been no published data describing the periodontal situation near interdental
      osteotomies after orthognatic surgery. The purpose of this study was to evaluate
      this situation. PATIENTS AND METHODS: Thirty patients with Class II malocclusions
      were studied 4 to 10 years after segmental orthognathic surgery, analyzing the
      periodontal condition near osteotomies with the aid of periapical and panoramic
      radiographs. RESULTS: Fifty-one pathologic periodontal lesions were found in the
      74 segmental osteotomy sites. There were 35 segmental areas with osseous
      periodontal defects and 16 segmental areas with missing teeth. CONCLUSION: A high
      incidence of dental and periodontal trauma occurs in the region of segmental
      osteotomies after orthognathic surgery.

PMID- 9541340
TI  - Evaluation of trismus, bite force, and pressure algometry after third molar
      surgery: a placebo-controlled study of ibuprofen.
AB  - PURPOSE: This study evaluated trismus, bite force, and pressure algometry as
      measures of analgesic efficacy after third molar removal. PATIENTS AND METHODS:
      Fifty-seven patients (36 females and 21 males) developed at least moderate pain
      after surgical removal of a mandibular third molar and were given either
      ibuprofen, 400 mg (n = 26), or placebo (n = 31) in a double-blind study. Pain
      intensity and pain relief were rated on a five-point verbal rating scale during
      the 4-hour study period. Recordings of trismus, bilateral pressure pain detection
      and tolerance thresholds, and bite force were performed before surgery, at
      medication, and hourly for 4 hours. Changes in the functional variables were
      calculated as percent change from baseline (before surgery). RESULTS: The pain
      intensity and pain relief ratings showed significant differences between the
      ibuprofen- and placebo-treated patients in the 4-hour study period. The changes
      in trismus, bite force, and pressure pain thresholds were in accordance with
      these pain ratings. Pressure pain detection threshold on the operated side was
      significantly lower in the placebo-treated patients compared with the ibuprofen
      treated patients 2 and 3 hours after medication, whereas pressure tolerance
      threshold showed a significant difference after 2 hours. Bite force on the
      operated side was significantly less reduced 3 hours after treatment with
      ibuprofen when compared with placebo. CONCLUSIONS: The functional measures used
      support the results obtained by rating of pain intensity and pain relief, and
      could be of value as measures of the efficacy of an analgesic to reduce
      functional impairment caused by postoperative pain.

PMID- 9541341
TI  - Adaptations of the masticatory system after bilateral fractures of the mandibular
      condylar process.
AB  - PURPOSE: The objective of this investigation was to evaluate the adaptations that
      occur in the masticatory system after treatment of bilateral fractures of the
      mandibular condylar process. PATIENTS AND METHODS: Twenty-two patients (15 men
      and seven women) with bilateral condylar process fractures treated by open
      reduction and rigid internal fixation (n = 6), closed therapy (n = 14), or a
      combination of these techniques (n = 2) were compared with 22 sex- and age
      matched controls. Measures of mandibular range of motion, bite force, muscle
      activity, estimated joint forces, and skeletal morphology were determined at 6
      weeks, 6 months, and 1, 2, and 3 years after treatment in all subjects. Various
      statistical tests were used for comparing differences between patients and
      controls. RESULTS: There was no significant difference in the patients'
      morphologic measures for the open and closed reduction procedures; therefore, all
      of these patients were tested as a single group. After treatment, patients had
      significantly increased mandibular plane and gonial angles and decreased facial
      axis angles. They also showed a significant reduction in posterior facial height
      and moment arm length for the masseter and pterygoid muscles. Anterior and
      posterior temporalis muscle direction also was significantly different between
      patients and controls. Patients had significantly limited mobility during the
      first year after fracture. Bite forces were lower for patients at all times and
      tooth positions, with a significant difference at 6 weeks after treatment.
      Patients had a tendency to use proportionally higher temporalis muscle activity
      during maximum biting; however, the differences were not statistically
      significant, probably because of the small sample size. The estimated joint force
      magnitudes were essentially identical between patients and controls; however, the
      direction of the patients' joint forces were more posteriorly directed for both
      incisor and molar bites. CONCLUSION: The results of this study suggest that early
      reduction in mandibular range of motion, bite force, and the distribution of
      masticatory muscle activity assist in preventing overloading of the bilaterally
      fractured mandibular condylar processes.

PMID- 9541342
TI  - Retrospective analysis of 35 patients with acinic cell carcinoma of the parotid
      gland.
AB  - PURPOSE: This retrospective study evaluated data pertaining to the history,
      symptoms, treatment, and prognosis of a series of patients treated for acinic
      cell carcinoma (ACC). PATIENTS AND METHODS: Data were based on the records of 35
      patients. Follow-up was done by analyzing their records and contacting the
      referring doctors. RESULTS: In 71% of the ACC patients, painful swelling of the
      lateral region of the face was the main symptom. Facial paralysis occurred in 11%
      of cases before treatment. Tumor recurrence after therapy was noted in 42% of
      cases. Highly differentiated ACC was the most frequent histologic subtype (74%).
      The grade of differentiation of the tumor was decisive for the prognosis. Highly
      differentiated ACC had a better prognosis (2 years overall survival, 100%; 5
      years overall survival, 83%; 10 years overall survival, 50%) than lowly
      differentiated tumors (2 years overall survival, 70%; 5 years overall survival,
      50%; 10 years overall survival, 30%). CONCLUSION: ACC is a rare tumor located
      mainly in the parotid gland that is characterized by some special attributes.
      Surgery is the therapy of choice. Prognosis depends mainly on the histologic
      subtype.

PMID- 9541343
TI  - Use of free fibula flap in patients with prior failed mandibular reconstruction.
AB  - PURPOSE: The purpose of this study was to assess the efficacy of the free fibula
      flap in patients who had failed prior attempts at bony reconstruction. PATIENTS
      AND METHODS: The records of all patients who had undergone free fibula
      reconstruction for segmental mandibular resections between 1993 and 1995 were
      retrospectively reviewed. Patients were divided into group I (14 patients who had
      failed previous bony reconstruction attempts) and group II (50 patients who had
      no previous reconstruction), and the two groups were compared. RESULTS: No
      statistical differences were found between group I and group II for mean age,
      mean hospital stay, mean intensive care unit stay, mean operating room time, mean
      intraoperative blood loss, mean colloid usage, or mean blood units transfused.
      Although group I had a statistically higher proportion of both patients with
      osteoradionecrosis and those receiving hyperbaric oxygen therapy (HBO), the
      number with a history of radiation therapy was not different in the two groups.
      Wound complication rates were not statistically different between groups I and II
      for all patients, or between those group I patients who did or did not receive
      HBO therapy. CONCLUSION: There was no increase in wound complications in the
      patients who had failed prior bony reconstructive attempts who underwent free
      fibula flaps. The free fibula flap is suggested as the reconstructive method of
      choice in this patient population.

PMID- 9541344
TI  - Propofol and fentanyl compared with midazolam and fentanyl during third molar
      surgery.
AB  - PURPOSE: The purpose of this study was to measure the safety and efficacy of
      propofol combined with fentanyl as sedative agents during third molar outpatient
      surgery. PATIENTS AND METHODS: A double-blind, prospective, randomized clinical
      trial involving 57 patients undergoing removal of third molars under intravenous
      sedation between November 1994 and December 1995 was performed. Patients randomly
      received either propofol and fentanyl (P + F, th = 24) or midazolam and fentanyl
      (M + F, M = 33). Patient demographics, Corah anxiety scores, and physiologic
      parameters were determined preoperatively. All medications were titrated to the
      same clinical end point for sedation. Intraoperative physiologic parameters,
      cooperation, alertness, and pain scores were assessed. Postoperative recovery and
      degree of amnesia also were determined. RESULTS: There were no significant
      differences in either patient demographics or surgical characteristics between
      groups. The P + F group was significantly less cooperative than the M + F group.
      Pain during injection of propofol was a significant adverse side effect. Both
      groups experienced a small percentage of apneic episodes, but mechanical
      ventilation was never required. There were no differences in recovery between
      groups as measured by the Treiger dot test and psychomotor recovery scores. The
      degree of anterograde amnesia was greater for the M + F group, although the
      difference was not statistically significant. Sedation was rated good to
      excellent by the patient, surgeon, and observer, and there were no statistically
      significant differences between groups. CONCLUSION: Propofol appears to be a safe
      and efficacious drug for use during outpatient oral surgical procedures.

PMID- 9541345
TI  - Detection of radiation-induced, accelerated atherosclerosis in patients with
      osteoradionecrosis by panoramic radiography.
AB  - PURPOSE: Osteoradionecrosis (ORN) of the mandible has long been considered the
      most destructive complication of head and neck irradiation. Recently, therapeutic
      irradiation has been implicated as the cause of induced/accelerated
      atherosclerosis of the cervical carotid artery and subsequent stroke. Panoramic
      radiography, previously shown to be capable of identifying carotid artery
      atherosclerosis in nonirradiated individuals, was used to assess the carotid
      vasculature of patients being treated for ORN. PATIENTS AND METHODS: The
      panoramic radiographs of 61 men (mean age, 60.5 years; range, 41 to 77 years) who
      received therapeutic irradiation to the neck 36 months or more previously were
      assessed for the presence of carotid artery atherosclerotic lesions. Sixty-one
      control subjects who never received therapeutic irradiation, but who were
      similarly susceptible to atherosclerosis by virtue of age, were assessed in a
      like manner. RESULTS: The irradiated individuals sustained a dose of 40 to 72 Gy
      to the area of the carotid bifurcation. Seventeen individuals (27.9%) with an
      irradiation dosage to the carotid bifurcation that averaged 59.2 Gy had a
      panoramic radiograph with a carotid atheroma (11 with unilateral lesions and six
      with bilateral lesions). The radiographs of the control subjects showed that
      three individuals (4.9%) had calcified carotid lesions. The mean age of these
      subjects was 66.1 years; two had unilateral lesions, and one had bilateral
      lesions. The difference in the proportion of individuals with ORN who manifested
      carotid artery atherosclerosis on their panoramic radiographs was statistically
      significant (P = .001) when compared with the nonirradiated control subjects. The
      lesions seen in both populations had a similar morphologic appearance and were
      radiographically located within the soft tissues of the neck 1.5 to 4.0 cm
      inferior-posterior to the angle of the mandible. CONCLUSIONS: Individuals with
      radiation doses sufficient to cause osteoradionecrosis of the mandible are at
      significantly higher risk of developing carotid artery atherosclerotic lesions
      than age-matched, nonirradiated controls.

PMID- 9541347
TI  - Comparison of fixation strengths of locking head and conventional screws, in
      fracture and reconstruction models.
AB  - PURPOSE: Claimed clinical advantages of the locking-head mandibular
      reconstruction plating system include the ability to achieve stability with fewer
      numbers of screws per bony segment as compared with conventional screws. The
      purpose of this study was to test the hypothesis that increased resistance to
      displacement will be obtained when using locking-head as compared with the same
      number of conventional screws per segment in both fracture and reconstruction
      models. MATERIALS AND METHODS: Eight groups were tested based on the screw number
      (two or four), screw type (locking-head or conventional), and fracture (bony
      apposition) or reconstruction model (1-cm defect). Two-dimensional beam mechanics
      using adult bovine ribs and the Instron machine were used to develop a load
      displacement curve up to 150 N for each specimen. An osteotomy was then created
      and the segments were reduced, with preload (fracture model) or with a 1-cm
      defect (reconstruction model), and plated using the Synthes locking-head plate
      with either two or four bicortical locking-head (4.0-mm) or conventional (2.7-mm)
      screws per segment. The fixed ribs were loaded to 150 N, and the displacement was
      recorded. RESULTS: Locking-head screws provided superior resistance when using
      two screws per segment in the reconstruction model as compared with conventional
      screws. Minimal difference was seen between other screw types within a model. The
      fracture model offered significantly greater (3.1 to 3.7X) resistance to
      displacement than did the reconstruction model. CONCLUSIONS: Locking-head screws
      provided significantly increased resistance to displacement when only two screws
      per segment were used in the reconstruction model. When four screws per segment
      were used, there was no significant difference between locking-head and
      conventional screw types in either model. The effect of bony buttressing is
      significant and may explain why miniplates often fail in the atrophic mandible
      but are successful in the fully dentate patient.

PMID- 9541346
TI  - Reconstruction of residual alveolar cleft defects with one-stage mandibular bone
      grafts and osseointegrated implants.
AB  - PURPOSE: This study evaluates a treatment regimen for reconstruction of residual
      maxillary alveolar cleft defects consisting of mandibular bone grafting and
      immediate implant installation. PATIENTS AND METHODS: Sixteen cleft patients
      (five female and 11 male) had residual cleft defects of the alveolar ridge
      reconstructed with bone grafts from the mandibular symphyseal region. The bone
      graft was pretapped at the donor site before fixation in the residual ridge with
      Branemark implants. Twenty implants were installed according to this concept. The
      period of observation ranged from 36 to 69 months, with a mean of 48 months after
      implant installation. RESULTS: Five patients developed wound dehiscenses that
      resulted in total or partial bone graft sequestration. Two implants were lost,
      one due to sequestration and the other due to mobility at the abutment procedure;
      18 implants were still well functioning at the end of the observation period.
      However, all patients showed significant periimplant bone resorption after this
      one-stage treatment. CONCLUSION: Because of the observed complication rate, the
      one-stage procedure may not be optimal for reconstructing residual cleft defects.

PMID- 9541348
TI  - Human immunodeficiency virus activity in rib allografts.
AB  - PURPOSE: The use of bone allografts involves the risk of transmitting infectious
      agents from the donor to the recipient as shown by historical surveys. A study
      was therefore undertaken to test the hypothesis that human immunodeficiency virus
      (HIV) activity can still be present after the freezing and thawing of ribs taken
      from an acquired immune deficiency syndrome (AIDS) patient at autopsy. MATERIALS
      AND METHODS: Rib samples were harvested under sterile conditions and frozen at 
      80 degrees C. After different freezing periods, the samples were cultured with
      activated lymphocytes. P24 antigen determination in the supernatant fluid was
      used to test for viral activity. RESULTS: Confirmation of viral activity was
      obtained after freezing periods ranging from 1 to 12 weeks. CONCLUSIONS: HIV
      activity can be found in ribs of AIDS patients, and this outlives the
      cryoprotection of bone banking. Donor selection remains the main security in the
      use of frozen bone allografts.

PMID- 9541349
TI  - Resorption of the mandibular condyle in a 6-year-old child.

PMID- 9541350
TI  - Extensive malakoplakia of the nasopharynx: management of a rare disease.

PMID- 9541351
TI  - Time-related changes in a case of torus palatinus.

PMID- 9541352
TI  - Peritemporomandibular abscess as a complication of acupuncture: a case report.

PMID- 9541353
TI  - The dental, craniofacial, and biochemical features of pyknodysostosis: a report
      of three new cases.

PMID- 9541354
TI  - Leiomyosarcoma of the buccal mucosa: a case report.

PMID- 9541355
TI  - Septic arthritis of the temporomandibular joint after the removal of third
      molars.

PMID- 9541356
TI  - Correction of congenital malar hypoplasia using stereolithography for presurgical
      planning.

PMID- 9541357
TI  - An unusual presentation of metastatic prostate cancer.

PMID- 9541358
TI  - Legally protecting the scope of oral and maxillofacial surgery.

PMID- 9541360
TI  - Dynamics of environmental supplementation of iodine: four years' experience of
      iodination of irrigation water in Hotien, Xinjiang, China.
AB  - Hotien prefecture, Xinjiang Province, China, in the Taklamakan Desert, is an area
      of severe iodine deficiency. Because usual methods of iodine supplementation
      failed here, we began supplementation in 1992 with potassium iodate, which was
      added to irrigation water (Lancet 1994; 334:107-110). We report 4 y experience
      with this method in 3 townships that contained a total treated population of
      37,000. Potassium iodate was dripped into irrigation water (to a concentration 10
      80 microg/l) during a 2- to 4-wk period. During the 3 y that followed, no further
      supplementation was made, and iodine concentrations increased several fold in
      crops and plants, sheep and chicken thyroid glands, and meat and in urine of
      children 2-6 y of age and of women who were of childbearing age. Infant mortality
      decreased 50%, and sheep production increased 43%. Iodine repletion of soil
      through irrigation water is an effective and cost-efficient way of providing
      iodine in appropriate situations.

PMID- 9541361
TI  - Serum organochlorine pesticide levels in patients with colorectal cancer in
      Egypt.
AB  - The widespread use of pesticides in Egypt, the high incidence of colorectal
      cancer in Egyptian children and young adults, and the published U.S. case reports
      in which pesticides have been connected with colorectal cancer led the authors to
      investigate the possible association between organochlorines and colorectal
      cancer. The authors conducted a pilot study to describe serum organochlorine
      levels among 31 Egyptian colorectal patients and 17 controls. High levels and
      large interindividual variability of p,p'-dichloro-diphenyldicholoroethylene
      (DDE), dichloro-diphenyl-trichloroanthane (DDT), beta-hexachlorocyclohexane (beta
      HCH), and hexachlorobenzene (HCB) levels were found among most subjects,
      especially those from rural areas. Farming and aging were each associated
      positively with high serum organochlorines. Colorectal cancer patients had higher
      serum organochlorines levels than controls. The high levels of organochlorines
      reported and their relation to age, residence, occupation, and disease status
      justify further study of the possible association between organochlorine
      pesticides and colorectal cancer in a larger population in Egypt.

PMID- 9541362
TI  - Maternal residential exposure to hazardous wastes and risk of central nervous
      system and musculoskeletal birth defects.
AB  - The authors used a case-control design to evaluate the risk of central nervous
      system and musculoskeletal birth defects relative to exposure to solvents, metal,
      and pesticide contaminants from hazardous waste sites. Cases included 473 central
      nervous-system-defect births and 3305 musculoskeletal-defect births to residents
      of 18 counties in New York State; controls comprised 12,436 randomly chosen
      normal births. For each address at birth, the authors assigned a probability of
      exposure to solvents, metals, and pesticides from hazardous waste sites in the
      study area (n = 643). They also rated residences by proximity to air releases
      from industrial facilities and by contamination of community water supplies.
      Compared with individuals for whom a low probability of exposure existed, mothers
      who resided in areas assigned a medium or high probability of exposure to
      hazardous waste contaminants did not show an increased risk of either type of
      birth defects. After adjusting for mother's race and age, prenatal care
      initiation, and population density, the resulting relative risks were as follows:
      central nervous system defects and exposure to solvents, 0.8 (95% confidence
      interval [CI] = .4, .6); central nervous system and metals, 1.0 (95% CI = 0.7,
      1.7); musculoskeletal defects and solvents, 0.9 (95% CI = 0.5, 1.3); and
      musculoskeletal defects and pesticides, .8 (95% CI = .5, 1.3). With respect to
      central nervous system defects, there was an elevated risk associated with living
      near industrial facilities that emitted solvents (odds ratio = 1.3 [95% CI = 1.0,
      1.7]) or metals (OR = 1.4, [95% CI = 1.0, 1.8]) into the air. The low proportion
      of individuals who had a medium or high probability of residential exposure to
      hazardous waste-site contaminants limited the investigation of particular
      pathways, disease subgroups, and/or geographic areas. Associations between
      central nervous system defects and industrial releases of solvents and metals
      need to be investigated further.

PMID- 9541363
TI  - Induced production of nitric oxide, tumor necrosis factor, and interleukin-6 in
      RAW 264.7 macrophages by streptomycetes from indoor air of moldy houses.
AB  - Dampness and mold growth in buildings cause spore generation into indoor air,
      which is associated with respiratory tract disorders. Specific agents or cellular
      mechanisms of diseases have not yet been identified. In this study, airborne
      spores of Streptomyces sp., isolated from moldy houses, stimulated RAW264.7
      macrophages, which produced tumor necrosis factor alpha and interleukin-6 and
      induced the expression of inducible nitric oxide synthase, with subsequent nitric
      oxide production. Spores of other microorganisms typically found in moldy houses
      did not markedly increase the production of these inflammatory mediators. The
      data implied a mechanism by which Streptomyces sp. may lead to respiratory tract
      disorders in individuals who live in moldy houses.

PMID- 9541364
TI  - Toxic effects of air freshener emissions.
AB  - To evaluate whether emissions of a commercial air freshener produced acute toxic
      effects in a mammalian species, the authors allowed male Swiss-Webster mice to
      breathe the emissions of one commercial-brand solid air freshener for 1 h.
      Sensory irritation and pulmonary irritation were evaluated with the ASTM-E-981
      test. A computerized version of this test measured the duration of the break at
      the end of inspiration and the duration of the pause at the end of expiration-
      two parameters subject to alteration via respiratory effects of airborne toxins.
      Measurements of expiratory flow velocity indicated changes in airflow limitation.
      The authors then subjected mice to a functional observational battery, the
      purpose of which was to probe for changes in nervous system function. Emissions
      of this air freshener at several concentrations (including concentrations to
      which many individuals are actually exposed) caused increases in sensory and
      pulmonary irritation, decreases in airflow velocity, and abnormalities of
      behavior measured by the functional observational battery score. The test
      atmosphere was subjected to gas chromatography/mass spectroscopy, and the authors
      noted the presence of chemicals with known irritant and neurotoxic properties.
      The Material Safety Data Sheet for the air freshener indicated that there was a
      potential for toxic effects in humans. The air freshener used in the study did
      not diminish the effect of other pollutants tested in combination. The results
      demonstrated that the air freshener may have actually exacerbated indoor air
      pollution via addition of toxic chemicals to the atmosphere.

PMID- 9541365
TI  - Associations between outdoor air pollution and daily mortality in Brisbane,
      Australia.
AB  - The results of several studies have indicated significant associations between
      daily mortality and air pollution, with little evidence of a threshold. In the
      current study, the authors examined daily mortality during the period 1987-1993
      for the Brisbane region, which is the fastest-growing urban region in Australia
      (annual average concentration of particulate matter less than 10 microm in
      diameter = 27 microg/m3, maximum hourly sulfur dioxide level = 60 ppb, and
      maximum daily ozone hourly level = 118 ppb). The authors conducted a general
      estimating equation analysis, and they used autoregressive Poisson models for
      daily mortality to examine associations with air pollution variables. The authors
      used research methods developed in the Air Pollution on Health, European Approach
      (APHEA), project to control confounding effects of weather and temporal trends.
      The air pollutants examined included particulate pollution (measured by
      nephelometry [bsp data]), sulfur dioxide, ozone, and nitrogen dioxide. The
      results indicated that the associations between total daily mortality and
      particulate levels found in studies in the United States and other countries may
      be applicable in Brisbane, Australia. Ozone levels were also associated
      significantly with total daily mortality. There was little evidence of
      interaction between the ozone effects (mainly in summer) and particulates or with
      sulfur dioxide and nitrogen dioxide. The associations between pollutants (ozone,
      bsp) and daily mortality were significant only for individuals who were older
      than 65 y of age; positive associations were also found with cardiovascular
      disease categories, and the regression coefficients--when significant--were
      higher than those for total mortality. The results indicated a possible threshold
      for ozone levels, but a similar result for particulate levels was not apparent.

PMID- 9541366
TI  - Effects of ambient particulate matter and ozone on daily mortality in Rotterdam,
      The Netherlands.
AB  - The association between daily variations in all-cause mortality from 1983-1991 in
      Rotterdam, the Netherlands, and ambient air pollution was investigated. Twenty
      four-hour average concentrations of total suspended particulates, Black Smoke,
      ozone, sulfur dioxide, and carbon monoxide were available on a daily basis. Every
      other day, total iron content in total suspended particulates samples was
      available. Poisson regression analysis was used to study associations between air
      pollution and mortality; generalized additive models were used to adjust for
      confounders (e.g., seasonal trends, weather). Daily mortality was associated most
      consistently with previous-day concentrations of total suspended particulates
      (relative risk = 1.05 for a change of 91 microg/m3) and ozone (relative risk =
      1.06 for a change of 67 microg/m3). Total iron was associated less consistently
      with mortality than total suspended particulate mass was. The associations of
      mortality with ozone and total suspended particulates were independent of sulfur
      dioxide and carbon monoxide. The relative risks of total suspended particulates
      and particularly ozone were higher for subjects older than 78 y. The relationship
      between mortality and ozone did not deviate significantly from linear. The
      relationship between mortality and total suspended particulates was linear below
      100 microg/m3 and leveled off at higher concentrations. If a threshold exists for
      the effects on mortality of these components, it exists at very low levels.

PMID- 9541367
TI  - Human nickel exposure in an area polluted by nickel refining: the Sor-Varanger
      study.
AB  - Sor-Varanger municipality in northern Norway is located close to two Russian
      nickel refineries that cause nickel and sulfur dioxide pollution. To investigate
      individual nickel exposure and possible health effects from the pollution, the
      authors invited all adults who were 18-69 y of age to a health survey in 1994.
      Urine samples were collected from 3671 participants (participation rate = 59.4%),
      and nickel concentrations were determined for 902 of them. Mean and median nickel
      concentrations were 0.9 microg/l and 0.6 microg/l, respectively. Individuals who
      lived in the rural areas closest to the refineries had lower nickel
      concentrations than individuals who lived in the more urban areas. Independent
      risk factors for nickel concentrations in urine were (a) being an urban dweller
      and (b) living close to areas with high-density traffic. The authors concluded
      that nickel exposure attributable to air pollution from Russian refineries was of
      minor importance for people who lived in Sor-Varanger.

PMID- 9541368
TI  - Effect of lead on fetal growth in a Canadian smelter city, 1961-1990.
AB  - The fetuses of women who live adjacent to a large lead smelter may experience
      intrauterine growth retardation that results from the mothers' systemic
      availability of lead absorbed from their environment. In this study, the authors
      used 30 y of birth records (n = 9329) to obtain fetal growth measurements for the
      smelter city and a suitable control city. The authors determined rates of
      intrauterine growth retardation (small-for-date births) for 5-y periods, and they
      determined the estimated relative risk of intrauterine growth retardation that
      occurred in the smelter city and compared it with the control city. The risk of
      intrauterine growth retardation for women in the smelter city was not
      significantly greater (odds ratio = 0.83) for either the 30-y period or each of
      the 5-y periods (odds ratio range = 0.51-1.33). The authors concluded that fetal
      growth was not affected by the amount of lead absorbed by women who lived in a
      smelter environment.

PMID- 9541369
TI  - Hair methylmercury levels in U.S. women.
AB  - The scientific community has recently focused its concerns on possible
      developmental delays in infants exposed to methylmercury via maternal fish
      consumption. In this study, the authors reported levels of methylmercury in hair
      specimens that corresponded to 2820 monthly seafood consumption diaries recorded
      by U.S. women of childbearing age. In this study, the geometric mean hair
      methylmercury level for diarists who reported some seafood consumption was 0.36
      ppm (one geometric standard deviation [GSD] range = 0.14-0.90 ppm); the
      corresponding value for diarists who reported no seafood consumption was 0.24 ppm
      (one GSD range = 0.09-0.62 ppm). Therefore, the mean hair methylmercury level
      associated with seafood consumption was 0.12 ppm (one GSD range = 0.05-0.32 ppm).
      The results of this study provide evidence that levels of methylmercury in the
      U.S. population are quite low. There is a significant contribution to hair
      methylmercury from sources other than seafood. It is not likely that maternal
      hair methylmercury levels in the range found in our study would be associated
      with adverse health effects in children.

PMID- 9541370
TI  - A comparison of physicians' and patients' attitudes toward pharmaceutical
      industry gifts.
AB  - OBJECTIVE: To compare physicians' and their patients' attitudes toward
      pharmaceutical gifts. DESIGN: Survey of physicians and their patients. SETTING:
      Two tertiary-care medical centers, one military and one civilian. PARTICIPANTS:
      Two hundred sixty-eight of 392 consecutively surveyed physicians, 100 of 103
      randomly selected patients at the military center, and 96 patients in a
      convenience sample at the civilian center completed the survey. MEASUREMENTS:
      Participants rated 10 pharmaceutical gifts on whether they were appropriate for
      physicians to accept and whether they were likely to influence prescribing.
      Patients found gifts less appropriate and more influential than did their
      physicians. About half of the patients were aware of such gifts; of those
      unaware, 24% responded that this knowledge altered their perception of the
      medical profession. Asked whether they thought their own physician accepted
      gifts, 27% said yes, 20% no, and 53% were unsure. For patients, feeling that
      gifts were inappropriate was best predicted by a belief that gifts might
      influence prescribing, while for physicians, the best predictor was knowledge of
      guidelines. CONCLUSIONS: Patients feel pharmaceutical gifts are more influential
      and less appropriate than do their physicians. Physicians may want to consider
      this in deciding whether to accept particular gifts. Broader dissemination of
      guidelines may be one means of changing physician behavior. At the same time,
      future guidelines should further consider the potentially different viewpoints of
      patients and physicians.

PMID- 9541371
TI  - Oral versus written feedback in medical clinic.
AB  - OBJECTIVE: To determine whether residents perceived oral, face-to-face feedback
      about their continuity clinic performance as better than a similar, written
      version. DESIGN: Single-blind, randomized controlled trial. SETTING: Two
      university-based, internal medicine residency clinics. PARTICIPANTS: All 68
      internal medicine and combined program (medicine-pediatrics, medicine-psychiatry,
      medicine-neurology, and preliminary year) residents and their clinic preceptors.
      MEASUREMENTS AND MAIN RESULTS: Residents at each program were separately
      randomized to oral or written feedback sessions with their clinic preceptors. The
      oral and written sessions followed similar, structured formats. Both groups were
      later sent questionnaires about aspects of the clinic. Sixty-five (96%) of the
      residents completed the questionnaire. Eight of the 19 questions dealt with
      aspects of feedback. A feedback scale was developed from the survey responses to
      those eight questions (alpha = .86). There were no significant differences in the
      responses to individual questions or in scale means (p > .20) between the two
      feedback groups. When each university was analyzed separately, one had a higher
      scale mean (3.10 vs 3.57, p = .047), but within each university, there were no
      differences between the oral and written feedback groups (p > .20). CONCLUSIONS:
      No differences were observed between the oral and written feedback groups. In
      attempting to provide better feedback to their residents, medical educators may
      better apply their efforts to other aspects, such as the frequency of their
      feedback, rather than the form of its delivery.

PMID- 9541372
TI  - Health-related quality of life in men with erectile dysfunction.
AB  - OBJECTIVE: To assess health-related quality of life (HRQOL) in men with erectile
      dysfunction. DESIGN: Descriptive survey with general and disease-specific
      measures. The instrument contained three established, validated HRQOL measures, a
      validated comorbidity checklist, and sociodemographics. The RAND 36-Item Health
      Survey 1.0 (SF-36) was used to assess general HRQOL. Sexual function and sexual
      bother were assessed using the UCLA Prostate Cancer Index. The marital
      interaction scale from the Cancer Rehabilitation Evaluation System Short Form
      (CARES-SF) was used to assess each patient's relationship with his sexual
      partner. SETTING: Urology clinics at a university medical center and the
      affiliated Veterans Affairs (VA) Medical Center. PARTICIPANTS: Thirty-five (67%)
      of 54 consecutive university patients presenting for erectile dysfunction and 22
      (42%) of 52 VA patients who were awaiting a previously prescribed vacuum erection
      device participated. MAIN RESULTS: The university respondents scored slightly
      lower than population normals in social function, role limitations due to
      emotional problems, and emotional well-being. The VA respondents scored lower
      than expected in all eight domains. Scores for the VA population were
      significantly lower than those for the university population in physical
      function, role limitations due to physical problems, bodily pain, and social
      function. A significant correlation was seen between marital interaction and
      sexual function (r = -.33, p = .01) but not between marital interaction and
      sexual bother (r = -.15, p = .26) in the total sample. Sexual function also
      correlated significantly with general health perceptions (r = .34, p = .01), role
      limitations due to physical problems (r = .29, p = .03), and role limitations due
      to emotional problems (r = .30, p = .03). Sexual bother did not correlate with
      any of the general HRQOL domains. Affluent men reported better sexual function (p
      = .03). CONCLUSIONS: The emotional domains of the SF-36 are associated with more
      profound impairment than are the physical domains in men with erectile
      dysfunction. Erectile dysfunction and the bother it causes are discrete domains
      of HRQOL and distinct from each other in these patients. With increased attention
      to patient-centered medical outcomes, greater emphasis has been placed on such
      variables as HRQOL. This should be particularly true for a patient-driven
      symptom, such as erectile dysfunction.

PMID- 9541373
TI  - Ethnic comparison of attitudes and beliefs about cigarette smoking.
AB  - OBJECTIVE: To determine if hypothesized differences in attitudes and beliefs
      about cigarette smoking between Latino and non-Latino white smokers are
      independent of years of formal education and number of cigarettes smoked per day.
      DESIGN: Cross-sectional survey using a random digit dial telephone method.
      SETTING: San Francisco census tracts with at least 10% Latinos in the 1990
      Census. PARTICIPANTS: Three hundred twelve Latinos (198 men and 114 women) and
      354 non-Latino whites (186 men and 168 women), 18 to 65 years of age, who were
      current cigarette smokers participated. MEASUREMENTS AND MAIN RESULTS: Self
      reports of cigarette smoking behavior, antecedents to smoking, reasons to quit
      smoking, and reasons to continue smoking were the measures. Latino smokers were
      younger (36.6 vs 39.6 years, p < .01), had fewer years of education (11.0 vs 14.3
      years, p < .001), and smoked on average fewer cigarettes per day (9.7 vs 20.1, p
      < .001). Compared with whites, Latino smokers were less likely to report smoking
      "almost always or often" after 13 of 17 antecedents (each p < .001), and more
      likely to consider it important to quit for 12 of 15 reasons (each p < .001). In
      multivariate analyses after adjusting for gender, age, education, income, and
      number of cigarettes smoked per day, Latino ethnicity was a significant predictor
      of being less likely to smoke while talking on the telephone (odds ratio [OR]
      0.41; 95% confidence interval [CI] 0.26, 0.64), drinking alcoholic beverages (OR
      0.66; 95% CI 0.44, 0.99), after eating (OR 0.55; 95% CI 0.37, 0.81), or at a bar
      (OR 0.62; 95% CI 0.41, 0.94), and a significant predictor of being more likely to
      smoke at a party (OR 1.72; 95% CI 1.14, 2.60). Latino ethnicity was a significant
      predictor of considering quitting important because of being criticized by family
      (OR 1.93; 95% CI 1.26, 2.98), burning clothes (OR 1.57; 95% CI 1.02, 2.42),
      damaging children's health (OR 1.67; 95% CI 1.08, 2.57), bad breath (OR 2.07; 95%
      CI 1.40, 3.06), family pressure (OR 1.67; 95% CI 1.10, 2.60), and being a good
      example to children (OR 1.83; 95% CI 1.21, 2.76). CONCLUSIONS: Differences in
      attitudes and beliefs about cigarette smoking between Latinos and whites are
      independent of education and number of cigarettes smoked. We recommend that these
      ethnic differences be incorporated into smoking cessation interventions for
      Latino smokers.

PMID- 9541374
TI  - Comparing utilization of life-sustaining treatments with patient and public
      preferences.
AB  - OBJECTIVE: The movement for advance planning of end-of-life care was motivated in
      part by the assumption that medical intervention for terminally ill patients
      varies from what these patients would prefer. We examined the validity of this
      assumption by comparing actual life-sustaining treatment practices for patients
      in critical illness scenarios and surveyed patients' advance care preferences.
      MEASUREMENTS AND MAIN RESULTS: We selected at random and reviewed 7,400 inpatient
      medical records from a single urban teaching hospital during the period just
      prior to the Patient Self-Determination Act. Records of 198 patients with
      conditions that matched advance directive scenarios were examined, and practices
      to withhold or withdraw seven life-sustaining treatments were documented.
      Practices were compared with surveyed preferences of 102 members of the general
      public and 495 outpatients who were followed by the same physicians as the 198
      patients. Concordance of practices and preferences for the 19 surveyed
      outpatients who eventually fell into one of the scenarios was also evaluated. One
      hundred sixty-seven inpatient cases met review criteria for the scenario coma
      with a small chance of recovery. Hospital patients received medical interventions
      that were not consistently greater or less than the preferences of the surveyed
      outpatients or members of the general public. Resuscitation, the most frequently
      withheld treatment (94% of cases), was withheld more often than surveyed
      preferences to decline it (56% of outpatients, p < .001). Four treatments-
      mechanical breathing, artificial nutrition, major surgery, and hemodialysis--were
      utilized comparably to surveyed outpatients' preferences (range p = .704-.055).
      Antibiotics and artificial hydration were withheld (9% and 6%, respectively) less
      often than surveyed outpatient's prior preferences to decline them (48% and 52%,
      respectively, p < .001 for each). Conversely, treatments given to the 19 surveyed
      patients who subsequently developed one of the illness scenarios were often
      incongruent with the patients' prior preferences. Again, in some cases more
      interventions were provided (26 of 63 declined treatments were given), and in
      some cases less (10 of 21 desired treatments were withheld). CONCLUSIONS: This
      study does not support the assumption that, collectively, patients' advance care
      preferences are less interventionist than actual practices for patients in
      corresponding scenarios. Nevertheless, these results do support the assumption
      that life-sustaining treatment decisions do not conform well to individual
      patients' specific preferences. Progress in end-of-life care should focus on
      shared decision making at the patient-proxy-physician level rather than on
      overall life-sustaining treatments utilization.

PMID- 9541375
TI  - The interaction of patient perception of overmedication with drug compliance and
      side effects.
AB  - OBJECTIVE: Little is known about the significance of patient-perceived
      overmedication. We sought to determine its prevalence and relation to medication
      compliance, adverse drug reactions, health-related quality of life (HRQOL), and
      burden of illness. DESIGN: Analysis of self-reported questionnaire data.
      PATIENTS/PARTICIPANT: There were 1,648 participants in a longitudinal study of
      male veterans. INTERVENTION: Participants listed each of their medications with
      indication, missed doses, adverse reactions, and whether their amount of
      medication was "too much, the right amount, or too little." The survey included
      questions about medication adherence, "problems with medications," common
      symptoms, and screening questions for a number of chronic conditions. We assessed
      HRQOL with the Multiple Outcomes Study 36-Item Short Form Health Study (SF-36).
      MEASUREMENTS AND MAIN RESULTS: Of the 1,256 respondents, 1,007 (80%) had taken
      medication within 4 weeks. Forty (4%) thought they were taking too much. They
      reported a 1.6-fold increase in prescription medications, a 5-8 fold increase in
      adverse effects, a 1.5-2 fold decrease in compliance, an increase in each of
      seven measured symptoms, and a decrease in six of eight SF-36 domains (p < .05
      for all comparisons), the exceptions being the mental health and role-emotional
      scales. There was also a slight increase in the report of any chronic illness
      (95% vs 86%, p > .05). CONCLUSIONS: Patient perception of overmedication
      correlates with self-report of decreased compliance, adverse drug reactions,
      decreased HRQOL, and an increase in symptomatology that is compatible with
      unrecognized side effects of medication. Such patients warrant careful
      evaluation.

PMID- 9541376
TI  - Enthusiasm for primary care: comparing family medicine and general internal
      medicine.
AB  - OBJECTIVE: To compare attitudes and perceptions of primary care among faculty,
      students, and residents oriented toward family medicine (FM) and general internal
      medicine (GIM). DESIGN: Descriptive study using confidential telephone
      interviews. PARTICIPANTS: National stratified probability sample of FM and GIM
      faculty (n = 68), residents (n = 196), and students (n = 81). MEASUREMENTS AND
      MAIN RESULTS: We created indicators for attitudes toward primary care among the
      faculty that included perceptions of medical practice, experiences within the
      academic environment, and support for primary-care-oriented change. For the
      students and residents, we explored their perceptions of faculty and resident
      attitudes toward primary care, their perception of encouragement to enter primary
      care, and their satisfaction with training. Family medicine faculty showed more
      enthusiasm for primary care as manifested by their greater likelihood to endorse
      a primary care physician to manage a serious illness (FM 81.3% vs GIM 41.1%; p <
      .01), their strong encouragement of students to enter primary care (FM 86.2% vs
      GIM 36.3%; p < .01), and their greater support for primary-care-oriented changes
      in medical education (FM 56.8% vs GIM 14.7%; p < .01). Family medicine students
      and residents were more likely to perceive the primary care faculty as very
      satisfied with their work (FM 69.2% vs GIM 51.5%; p < .05), to feel strongly
      encouraged by peers toward primary care (FM 59.5% vs GIM 16.1%; p < .0001), and
      to have a primary care role model (FM 84.3% vs GIM 61.3%; p < .05). CONCLUSIONS:
      Family medicine faculty, students, and residents showed a consistent pattern of
      greater enthusiasm for primary care than their GIM counterparts. This may be a
      reflection of the different cultures of the two disciplines.

PMID- 9541377
TI  - Making use of qualitative research techniques.

PMID- 9541378
TI  - What predicts medical student career choice?
AB  - The literature on medical student career choice has identified several influences
      that can be categorized as student demographics, medical school characteristics,
      students' perceptions of specialty characteristics, and student-held values. A
      logistic regression model that included demographics, medical school, and student
      rated influences as a proxy for perceptions and values was used to determine
      their relative contribution to student career choice for three consecutive
      cohorts of senior medical students attending two schools (n = 649). This model
      identified a positive relation between choice of primary care career and both
      student-rated influences and one student demographic characteristic, but not
      between career choice and school attended. Variables positively correlated with
      primary care career choice were related to working with people and marital
      status. Negatively correlated variables were related to income and prestige.

PMID- 9541380
TI  - Free gifts: redundancy or conundrum?

PMID- 9541379
TI  - Delirium risk factors in elderly hospitalized patients.
AB  - OBJECTIVE: Delirium is frequent in elderly hospitalized patients. Many studies
      have examined its risk factors, but results have been quite variable. Thus, the
      goal of this study is to identify through systematic literature review the risk
      factors associated with the development of delirium in hospitalized geriatric
      patients. MEASUREMENTS AND MAIN RESULTS: First, MEDLINE/CURRENT CONTENTS
      databases were screened for relevant articles published from 1966 to December
      1995, and from bibliographies of identified articles additional reports were
      selected. Second, the reports were screened by two different investigators and
      retained only if meeting the five following criteria: (1) original research in
      French or English; (2) prospective study; (3) patients over age 50; (4) minimum
      of one risk factor examined; (5) acceptable definition of delirium. Third, the
      methodology of each study was graded according to specific criteria for risk
      factor studies. Fourth, risk factors were identified and tabulated, unadjusted
      odds ratios (ORs) were computed, and where appropriate a combined OR with the
      Mantel-Haenszel estimator was calculated. Twenty-seven articles were retained
      meeting all of the above criteria. Among these studies, 11 were done on medical
      patients, 9 on surgical patients, 2 on medical and surgical patients, and 5 on
      psychiatric patients. In total 1,365 subjects with delirium were studied. Sixty
      one different risk factors were examined, the five most common being dementia,
      medication, medical illness, age, and male gender. Mantel-Haenszel estimator was
      calculated for 10 risk factors, the most strongly associated being dementia (OR
      5.2; 95% confidence interval [CI] 4.2, 6.3), medical illness (OR 3.8; 95% CI 2.2,
      6.4), alcohol abuse (OR 3.3; 95% CI 1.9, 5.5), and depression (OR 1.9; 95% CI
      1.3, 2.6). Methodologic weaknesses were present in many studies. CONCLUSIONS:
      Despite methodologic limitations, certain risk factors for delirium seem to be
      consistent and could help identify high-risk patients. These risk factors include
      dementia, advanced age, and medical illness. Other risk factors appear to play a
      contributory role in the development of delirium in elderly hospitalized
      patients.

PMID- 9541381
TI  - Strangers in a strange land: primary care physicians in academic medical centers.

PMID- 9541382
TI  - Symptoms of hypothyroidism.

PMID- 9541383
TI  - Physicians' use of lumbar spine imaging tests.

PMID- 9541384
TI  - Mechanism and evolution of protein dimerization.
AB  - We have investigated the mechanism and the evolutionary pathway of protein
      dimerization through analysis of experimental structures of dimers. We propose
      that the evolution of dimers may have multiple pathways, including (1) formation
      of a functional dimer directly without going through an ancestor monomer, (2)
      formation of a stable monomer as an intermediate followed by mutations of its
      surface residues, and (3), a domain swapping mechanism, replacing one segment in
      a monomer by an equivalent segment from an identical chain in the dimer. Some of
      the dimers which are governed by a domain swapping mechanism may have evolved at
      an earlier stage of evolution via the second mechanism. Here, we follow the
      theory that the kinetic pathway reflects the evolutionary pathway. We analyze the
      structure-kinetics-evolution relationship for a collection of symmetric
      homodimers classified into three groups: (1) 14 dimers, which were referred to as
      domain swapping dimers in the literature; (2) nine 2-state dimers, which have no
      measurable intermediates in equilibrium denaturation; and (3), eight 3-state
      dimers, which have stable intermediates in equilibrium denaturation. The analysis
      consists of the following stages: (i) The dimer is divided into two structural
      units, which have twofold symmetry. Each unit contains a contiguous segment from
      one polypeptide chain of the dimer, and its complementary contiguous segment from
      the other chain. (ii) The division is repeated progressively, with different
      combinations of the two segments in each unit. (iii) The coefficient of
      compactness is calculated for the units in all divisions. The coefficients
      obtained for different cuttings of a dimer form a compactness profile. The
      profile probes the structural organization of the two chains in a dimer and the
      stability of the monomeric state. We describe the features of the compactness
      profiles in each of the three dimer groups. The profiles identify the swapping
      segments in domain swapping dimers, and can usually predict whether a dimer has
      domain swapping. The kinetics of dimerization indicates that some dimers which
      have been assigned in the literature as domain swapping cases, dimerize through
      the 2-state kinetics, rather than through swapping segments of performed
      monomers. The compactness profiles indicate a wide spectrum in the kinetics of
      dimerization: dimers having no intermediate stable monomers; dimers having an
      intermediate with a stable monomer structure; and dimers having an intermediate
      with a stable structure in part of the monomer. These correspond to the multiple
      evolutionary pathways for dimer formation. The evolutionary mechanisms proposed
      here for dimers are applicable to other oligomers as well.

PMID- 9541385
TI  - Subunit asymmetry in the three-dimensional structure of a human CuZnSOD mutant
      found in familial amyotrophic lateral sclerosis.
AB  - The X-ray crystal structure of a human copper/zinc superoxide dismutase mutant
      (G37R CuZnSOD) found in some patients with the inherited form of Lou Gehrig's
      disease (FALS) has been determined to 1.9 angstroms resolution. The two SOD
      subunits have distinct environments in the crystal and are different in structure
      at their copper binding sites. One subunit (subunit[intact]) shows a four
      coordinate ligand geometry of the copper ion, whereas the other subunit
      (subunit[broken]) shows a three-coordinate geometry of the copper ion. Also,
      subunit(intact) displays higher atomic displacement parameters for backbone atoms
      ((B) = 30 +/- 10 angstroms2) than subunit(broken) ((B) = 24 +/- 11 angstroms2).
      This structure is the first CuZnSOD to show large differences between the two
      subunits. Factors that may contribute to these differences are discussed and a
      possible link of a looser structure to FALS is suggested.

PMID- 9541386
TI  - Structures of murine carbonic anhydrase IV and human carbonic anhydrase II
      complexed with brinzolamide: molecular basis of isozyme-drug discrimination.
AB  - Carbonic anhydrase IV (CAIV) is a membrane-associated enzyme anchored to plasma
      membrane surfaces by a phosphatidylinositol glycan linkage. We have determined
      the 2.8-angstroms resolution crystal structure of a truncated, soluble form of
      recombinant murine CAIV. We have also determined the structure of its complex
      with a drug used for glaucoma therapy, the sulfonamide inhibitor brinzolamide
      (Azopt). The overall structure of murine CAIV is generally similar to that of
      human CAIV; however, some local structural differences are found in the active
      site resulting from amino acid sequence differences in the "130's segment" and
      the residue-63 loop (these may affect the nearby catalytic proton shuttle, His
      64). Similar to human CAIV, the C-terminus of murine CAIV is surrounded by a
      substantial electropositive surface potential that may stabilize the interaction
      with the phospholipid membrane. Binding interactions observed for brinzolamide
      rationalize the generally weaker affinity of inhibitors used in glaucoma therapy
      toward CAIV compared with CAII.

PMID- 9541388
TI  - Solvation studies of DMP323 and A76928 bound to HIV protease: analysis of water
      sites using grand canonical Monte Carlo simulations.
AB  - We examine the water solvation of the complex of the inhibitors DMP323 and A76928
      bound to HIV-1 protease through grand canonical Monte Carlo simulations, and
      demonstrate the ability of this method to reproduce crystal waters and
      effectively predict water positions not seen in the DMP323 or A76928 structures.
      The simulation method is useful for identifying structurally important waters
      that may not be resolved in the crystal structures. It can also be used to
      identify water positions around a putative drug candidate docked into a binding
      pocket. Knowledge of these water positions may be useful in designing drugs to
      utilize them as bridging groups or displace them in the binding pocket. In
      addition, the method should be useful in finding water sites in homology models
      of enzymes for which crystal structures are unavailable.

PMID- 9541387
TI  - Crystal structures of the psychrophilic alpha-amylase from Alteromonas
      haloplanctis in its native form and complexed with an inhibitor.
AB  - Alteromonas haloplanctis is a bacterium that flourishes in Antarctic sea-water
      and it is considered as an extreme psychrophile. We have determined the crystal
      structures of the alpha-amylase (AHA) secreted by this bacterium, in its native
      state to 2.0 angstroms resolution as well as in complex with Tris to 1.85
      angstroms resolution. The structure of AHA, which is the first experimentally
      determined three-dimensional structure of a psychrophilic enzyme, resembles those
      of other known alpha-amylases of various origins with a surprisingly greatest
      similarity to mammalian alpha-amylases. AHA contains a chloride ion which
      activates the hydrolytic cleavage of substrate alpha-1,4-glycosidic bonds. The
      chloride binding site is situated approximately 5 angstroms from the active site
      which is characterized by a triad of acid residues (Asp 174, Glu 200, Asp 264).
      These are all involved in firm binding of the Tris moiety. A reaction mechanism
      for substrate hydrolysis is proposed on the basis of the Tris inhibitor binding
      and the chloride activation. A trio of residues (Ser 303, His 337, Glu 19) having
      a striking spatial resemblance with serine-protease like catalytic triads was
      found approximately 22 angstroms from the active site. We found that this triad
      is equally present in other chloride dependent alpha-amylases, and suggest that
      it could be responsible for autoproteolytic events observed in solution for this
      cold adapted alpha-amylase.

PMID- 9541389
TI  - Crystallization of phycoerythrin 545 of Rhodomonas lens using detergents and
      unusual additives.
AB  - Phycoerythrin 545 from the cryptomonad alga, Rhodomonas lens, has been
      crystallized under a wide variety of conditions. Although this type of
      photosynthetic light-harvesting protein is water soluble, detergents were always
      required for crystallization. The crystals were typically poorly ordered, or
      ordered in only two dimensions. However, crystals that were well-ordered in three
      dimensions could be obtained under two different conditions. Both used
      polyethylene glycol as precipitant and the detergent lauryldimethylaminoxide, but
      the additives that were critical for obtaining well-ordered crystals were
      propionamide in one case and Cs+/Br- in the other. Crystals obtained in the
      presence of propionamide have the space group P2(1)2(1)2(1), with cell constants
      of a = 85.6 angstroms, b = 108.2 angstroms, and c = 131.0 angstroms, and contain
      two dimers [i.e., 2 x (alpha2beta2)] in the asymmetric unit. They show
      diffraction to at least 3.0 angstroms resolution. The crystals grown with Cs+/Br-
      are nearly isomorphous. Both types of crystals show intense, strongly polarized
      fluorescence, suggesting that energy transfer in the crystals is highly
      efficient. This should provide a basis for quantitative investigation of the role
      of exciton interactions in energy transfer in cryptomonad phycobiliproteins.

PMID- 9541390
TI  - A proposed architecture for lecithin cholesterol acyl transferase (LCAT):
      identification of the catalytic triad and molecular modeling.
AB  - The enzyme cholesterol lecithin acyl transferase (LCAT) shares the Ser/Asp
      Glu/His triad with lipases, esterases and proteases, but the low level of
      sequence homology between LCAT and these enzymes did not allow for the LCAT fold
      to be identified yet. We, therefore, relied upon structural homology calculations
      using threading methods based on alignment of the sequence against a library of
      solved three-dimensional protein structures, for prediction of the LCAT fold. We
      propose that LCAT, like lipases, belongs to the alpha/beta hydrolase fold family,
      and that the central domain of LCAT consists of seven conserved parallel beta
      strands connected by four alpha-helices and separated by loops. We used the
      conserved features of this protein fold for the prediction of functional domains
      in LCAT, and carried out site-directed mutagenesis for the localization of the
      active site residues. The wild-type enzyme and mutants were expressed in Cos-1
      cells. LCAT mass was measured by ELISA, and enzymatic activity was measured on
      recombinant HDL, on LDL and on a monomeric substrate. We identified D345 and H377
      as the catalytic residues of LCAT, together with F103 and L182 as the oxyanion
      hole residues. In analogy with lipases, we further propose that a potential "lid"
      domain at residues 50-74 of LCAT might be involved in the enzyme-substrate
      interaction. Molecular modeling of human LCAT was carried out using human
      pancreatic and Candida antarctica lipases as templates. The three-dimensional
      model proposed here is compatible with the position of natural mutants for either
      LCAT deficiency or Fish-eye disease. It enables moreover prediction of the LCAT
      domains involved in the interaction with the phospholipid and cholesterol
      substrates.

PMID- 9541391
TI  - Cadmium-induced crystallization of proteins: II. Crystallization of the
      Salmonella typhimurium histidine-binding protein in complex with L-histidine, L
      arginine, or L-lysine.
AB  - To further investigate favorable effects of divalent cations on the formation of
      protein crystals, three complexes of Salmonella typhimurium histidine-binding
      protein were crystallized with varying concentrations of cadmium salts. For each
      of the three histidine-binding protein complexes, cadmium cations were found to
      promote or improve crystallization. The optimal cadmium concentration is ligand
      specific and falls within a narrow concentration range. In each case, crystals
      grown in the presence of cadmium diffract to better than 2.0 angstroms resolution
      and belong to the orthorhombic space group P2(1)2(1)2(1). From our results and
      from the analysis of cadmium sites in well-refined protein structures, we propose
      that cadmium addition provides a generally useful technique to modify crystal
      morphology and to improve diffraction quality.

PMID- 9541392
TI  - Comparisons between the structures of HCV and Rep helicases reveal structural
      similarities between SF1 and SF2 super-families of helicases.
AB  - Three helicase structures have been determined recently: that of the DNA helicase
      PcrA, that of the hepatitis C virus RNA helicase, and that of the Escherichia
      coli DNA helicase Rep. PcrA and Rep belong to the same super-family of helicases
      (SF1) and are structurally very similar. In contrast, the HCV helicase belongs to
      a different super-family of helicases, SF2, and shows little sequence homology
      with the PcrA/Rep helicases. Yet, the HCV helicase is structurally similar to
      Rep/PcrA, suggesting preservation of structural scaffolds and relationships
      between helicase motifs across these two super-families. The comparison study
      presented here also reveals the existence of a new helicase motif in the SF1
      family of helicases.

PMID- 9541393
TI  - X-ray structures of three interface mutants of gammaB-crystallin from bovine eye
      lens.
AB  - GammaB-crystallin consists of two domains each comprising two "Greek key" motifs.
      Both domains fold independently, and domain interactions contribute significantly
      to the stability of the C-terminal domain. In a previous study (Palme S et al.,
      1996, Protein Sci 6:1529-1636) it was shown that Phe56 from the N-terminal
      domain, a residue involved in forming a hydrophobic core at the domain interface,
      effects the interaction of the two domains, and therefore, the stability of the C
      terminal domain. Ala or Asp at position 56 drastically decreased the stability of
      the C-terminal domain, whereas Trp had a more moderate effect. In this article we
      present the X-ray structures of these interface mutants and correlate them with
      the stability data. The mutations do not effect the overall structure of the
      molecule. No structural changes are observed in the vicinity of the replaced
      residue, suggesting that the local structure is too rigid to allow compensations
      for the amino acid replacements. In the mutants gammaB-F56A and -F56D, a solvent
      filled groove accessible to the bulk solvent is created by the replacement of the
      bulky Phe side chain. In gammaB-F56W, the pyrrole moiety of the indole ring
      replaces the phenyl side chain of the wild type. With the exception of gammaB
      F56W, there is a good correlation between the hydrophobicity of the amino acid at
      position 56 according to the octanol scale and the stability of the C-terminal
      domain. In gammaB-F56W, the C-terminal domain is less stable than estimated from
      the hydrophobicity, presumably because the ring nitrogen (Nepsilon1) has no
      partner to form hydrogen bonds. The data suggest that the packing of hydrophobic
      residues in the interface core is important for domain interactions and the
      stability of gammaB-crystallin. Apparently, for protein stability, the same
      principles apply for hydrophobic cores within domains and at domain interfaces.

PMID- 9541394
TI  - Solution structure of Compstatin, a potent complement inhibitor.
AB  - The third component of complement, C3, plays a central role in activation of the
      classical, alternative, and lectin pathways of complement activation. Recently,
      we have identified a 13-residue cyclic peptide (named Compstatin) that
      specifically binds to C3 and inhibits complement activation. To investigate the
      topology and the contribution of each critical residue to the binding of
      Compstatin to C3, we have now determined the solution structure using 2D NMR
      techniques; we have also synthesized substitution analogues and used these to
      study the structure-function relationships involved. Finally, we have generated
      an ensemble of a family of solution structures of the peptide with a hybrid
      distance geometry-restrained simulated-annealing methodology, using distance,
      dihedral angle, and 3J(NH-Halpha)-coupling constant restraints. The Compstatin
      structure contained a type I beta-turn comprising the segment Gln5-Asp6-Trp7
      Gly8. Preference for packing of the hydrophobic side chains of Val3, Val4, and
      Trp7 was observed. The generated structure was also analyzed for consistency
      using NMR parameters such as NOE connectivity patterns, 3J(NH-Halpha)-coupling
      constants, and chemical shifts. Analysis of Ala substitution analogues suggested
      that Val3, Gln5, Asp6, Trp7, and Gly8 contribute significantly to the inhibitory
      activity of the peptide. Substitution of Gly8 caused a 100-fold decrease in
      inhibitory potency. In contrast, substitution of Val4, His9, His10, and Arg11
      resulted in minimal change in the activity. These findings indicate that specific
      side-chain interactions and the beta-turn are critical for preservation of the
      conformational stability of Compstatin and they might be significant for
      maintaining the functional activity of Compstatin.

PMID- 9541395
TI  - Mutational analysis of human DNase I at the DNA binding interface: implications
      for DNA recognition, catalysis, and metal ion dependence.
AB  - Human deoxyribonuclease I (DNase I), an enzyme used to treat cystic fibrosis
      patients, has been systematically analyzed by site-directed mutagenesis of
      residues at the DNA binding interface. Crystal structures of bovine DNase I
      complexed with two different oligonucleotides have implicated the participation
      of over 20 amino acids in catalysis or DNA recognition. These residues have been
      classified into four groups based on the characterization of over 80 human DNase
      I variants. Mutations at any of the four catalytic amino acids His 134, His 252,
      Glu 78, and Asp 212 drastically reduced the hydrolytic activity of DNase I.
      Replacing the three putative divalent metal ion-coordinating residues Glu 39, Asp
      168, or Asp 251 led to inactive variants. Amino acids Gln 9, Arg 41, Tyr 76, Arg
      111, Asn 170, Tyr 175, and Tyr 211 were also critical for activity, presumably
      because of their close proximity to the active site, while more peripheral DNA
      interactions stemming from 13 other positions were of minimal significance. The
      relative importance of these 27 positions is consistent with evolutionary
      relationships among DNase I across different species, DNase I-like proteins, and
      bacterial sphingomyelinases, suggesting a fingerprint for a family of DNase I
      like proteins. Furthermore, we found no evidence for a second active site that
      had been previously implicated in Mn2+-dependent DNA degradation. Finally, we
      correlated our mutational analysis of human DNase I to that of bovine DNase I
      with respect to their specific activity and dependence on divalent metal ions.

PMID- 9541396
TI  - Role of the amino-terminal region of streptokinase in the generation of a fully
      functional plasminogen activator complex probed with synthetic peptides.
AB  - The mechanism whereby fragments of streptokinase (SK) derived from its N terminus
      (e.g., SK1-59 or SK1-63) enhance the low plasminogen (PG)-activating ability of
      other fragments, namely SK64-386, SK60-414, SK60-387, and SK60-333 (reported
      previously), has been investigated using a synthetic peptide approach. The
      addition of either natural SK1-59, or chemically synthesized SK16-59, at
      saturation (about 500-fold molar excess) generated amidolytic and PG activation
      capabilities in equimolar mixtures of human plasminogen (HPG) and its
      complementary fragment (either SK60-414 or SK56-414, prepared by expression of
      truncated SK gene fragments in Escherichia coli) that were approximately 1.2- and
      2.5-fold, respectively, of that generated by equimolar mixtures of native SK and
      HPG. Although in the absence of SK1-59 equimolar mixtures of SK56-414 and HPG
      could generate almost 80% of amidolytic activity, albeit slowly, less than 2%
      level of PG activation could be observed under the same conditions, indicating
      that the contribution of the N-terminal region lay mainly in imparting in SK56
      414 an enhanced ability for PG activation. The ability of various synthetic
      peptides derived from the amino-terminal region (SK16-51, SK16-45, SK37-59, SK1
      36, SK16-36, and SK37-51) to (1) complement equimolar mixtures of SK56-414 and
      HPG for the generation of amidolytic and PG activation functions, (2) inhibit the
      potentiation of SK56-414 and HPG by SK16-59, and (3) directly inhibit PG
      activation by the 1:1 SK-HPG activator complex was tested. Apart from SK16-59,
      SK16-51, and 16-45, the ability to rapidly generate amidolytic potential in HPG
      in the presence of SK56-414 survived even in the smaller SK-peptides, viz., SK37
      59 and SK37-51. However, this ability was abolished upon specifically mutating
      the sequence -LTSRP-, present at position 42-46 in native SK. Although SK16-51
      retained virtually complete ability for potentiation of PG activation in
      comparison to SK16-59 or SK1-59, this ability was reduced by approximately
      fourfold in the case of SK16-45, and completely abolished upon further truncation
      of the C-terminal residues to SK16-36 or SK1-36. Remarkably, however, these
      peptides not only displayed ability to bind PG, but also showed strong inhibition
      of PG activation by the native activator complex in the micromolar range of
      concentration; the observed inhibition, however, could be competitively relieved
      by increasing the concentration of substrate PG in the reaction, suggesting that
      this region in SK contains a site directed specifically toward interaction with
      substrate PG. This conclusion was substantiated by the observation that the
      potentiation of PG activating ability was found to be considerably reduced in a
      peptide (SK25-59) in which the sequence corresponding to this putative locus
      (residues 16-36) was truncated at the middle. On the other hand, fragments SK37
      51 and SK37-59 did not show any inhibition of the PG activation by native
      activator complex. Taken together, these findings strongly support a model of SK
      action wherein the HPG binding site resident in the region 37-51 helps in
      anchoring the N-terminal domain to the strong intermolecular complex formed
      between HPG and the region 60-414. In contrast, the site located between residues
      16 and 36 is qualitatively more similar to the previously reported PG interacting
      site (SK254-273) present in the core region of SK, in being involved in the
      relatively low-affinity enzyme-substrate interactions of the activator complex
      with PG during the catalytic cycle.

PMID- 9541397
TI  - Locally accessible conformations of proteins: multiple molecular dynamics
      simulations of crambin.
AB  - Multiple molecular dynamics (MD) simulations of crambin with different initial
      atomic velocities are used to sample conformations in the vicinity of the native
      structure. Individual trajectories of length up to 5 ns sample only a fraction of
      the conformational distribution generated by ten independent 120 ps trajectories
      at 300 K. The backbone atom conformational space distribution is analyzed using
      principal components analysis (PCA). Four different major conformational regions
      are found. In general, a trajectory samples only one region and few transitions
      between the regions are observed. Consequently, the averages of structural and
      dynamic properties over the ten trajectories differ significantly from those
      obtained from individual trajectories. The nature of the conformational sampling
      has important consequences for the utilization of MD simulations for a wide range
      of problems, such as comparisons with X-ray or NMR data. The overall average
      structure is significantly closer to the X-ray structure than any of the
      individual trajectory average structures. The high frequency (less than 10 ps)
      atomic fluctuations from the ten trajectories tend to be similar, but the lower
      frequency (100 ps) motions are different. To improve conformational sampling in
      molecular dynamics simulations of proteins, as in nucleic acids, multiple
      trajectories with different initial conditions should be used rather than a
      single long trajectory.

PMID- 9541398
TI  - Spider minor ampullate silk proteins contain new repetitive sequences and highly
      conserved non-silk-like "spacer regions".
AB  - Spider minor ampullate silk is a strong non-elastic deformably stretchable silk
      used in web formation. This silk from Nephila clavipes is composed of two
      proteins, MiSp 1 and 2, whose transcripts are 9.5 and 7.5 kb, respectively, as
      determined by Northern blots. Both MiSp proteins are organized into a
      predominantly repetitive region and a small nonrepetitive carboxy terminal
      region. These highly repetitive regions are composed mainly of glycine and
      alanine, but also contain tyrosine, glutamine, and arginine. The sequences are
      mainly GGX and GA repeats. The repetitive regions are interrupted by
      nonrepetitive serine-rich spacer regions. Although the sequences of the spacer
      regions differ from the repetitive regions, sequences of the spacers from
      different regions of the proteins are nearly identical. The sequence differences
      between major and minor ampullate silks may explain the differing mechanical
      properties of the fibers.

PMID- 9541399
TI  - Tetramer-dimer equilibrium of oxyhemoglobin mutants determined from auto
      oxidation rates.
AB  - One of the main difficulties with blood substitutes based on hemoglobin (Hb)
      solutions is the auto-oxidation of the hemes, a problem aggravated by the
      dimerization of Hb tetramers. We have employed a method to study the oxyHb
      tetramer-dimer equilibrium based on the rate of auto-oxidation as a function of
      protein concentration. The 16-fold difference in dimer and tetramer auto
      oxidation rates (in 20 mM phosphate buffer at pH 7.0, 37 degrees C) was exploited
      to determine the fraction dimer. The results show a transition of the auto
      oxidation rate from low to high protein concentrations, allowing the
      determination of the tetramer-dimer dissociation coefficient K4,2 = [Dimer]
      2/[Tetramer]. A 14-fold increase in K4,2 was observed for addition of 10 mM of
      the allosteric effector inositol hexaphosphate (IHP). Recombinant hemoglobins
      (rHb) were genetically engineered to obtain Hb with a lower oxygen affinity than
      native Hb (Hb A). The rHb alpha2beta2 [(C7) F41Y/(G4) N102Y] shows a fivefold
      increase in K4,2 at pH 7.0, 37 degrees C. An atmosphere of pure oxygen is
      necessary in this case to insure fully oxygenated Hb. When this condition is
      satisfied, this method provides an efficient technique to characterize both the
      tetramer-dimer equilibrium and the auto-oxidation rates of various oxyHb. For low
      oxygen affinity Hb equilibrated under air, the presence of deoxy subunits
      accelerates the auto-oxidation. Although a full analysis is complicated, the auto
      oxidation studies for air equilibrated samples are more relevant to the
      development of a blood substitute based on Hb solutions. The double mutants, rHb
      alpha2beta2 [(C7) F41Y/(G4) N102A] and rHb alpha2beta2 [(C7) F41Y/(E10) K66T],
      show a lower oxygen affinity and a higher rate of oxidation than Hb A.
      Simulations of the auto-oxidation rate versus Hb concentration indicate that very
      high protein concentrations are required to observe the tetramer auto-oxidation
      rate. Because the dimers oxidize much more rapidly, even a small fraction dimer
      will influence the observed oxidation rate.

PMID- 9541400
TI  - The methanol-induced transition and the expanded helical conformation in hen
      lysozyme.
AB  - Methanol-induced conformational transitions of hen egg white lysozyme were
      investigated with a combined use of far- and near-UV CD and NMR spectroscopies,
      ANS binding and small-angle X-ray scattering. Addition of methanol induced no
      global change in the native conformation itself, but induced a transition from
      the native state to the denatured state which was highly cooperative, as shown by
      the coincidence of transition curves monitored by the far- and near-UV CD
      spectroscopy, by isodichroic points in the far- and near-UV CD spectra and by the
      concomitant disappearance of individual 1H NMR signals of the native state. The
      ANS binding experiments could detect no intermediate conformer similar to the
      molten globule state in the process of the methanol denaturation. However, at
      high concentration of methanol, e.g., 60% (v/v) methanol/water, a highly helical
      state (H) was realized. The H state had a helical content much higher than the
      native state, monitored by far-UV CD spectroscopy, and had no specific tertiary
      structure, monitored both by near-UV CD and NMR spectroscopy. The radius of
      gyration in the H state, 24.9 angstroms, was significantly larger than that in
      the native state (15.7 angstroms). The Kratky plot for the H state did not show a
      clear peak and was quite similar to that for the urea-denatured state, indicating
      a complete lack of globularity. Thus we conclude that the H state has a
      considerably expanded, flexible broken rod-like conformation which is clearly
      distinguishable from the "molten globule" state. The stability of both N and H
      states depends on pH and methanol concentration. Thus a phase diagram involving N
      and H was constructed.

PMID- 9541401
TI  - Anion binding to the ubiquitin molecule.
AB  - Effects of different salts (NaCl, MgCl2, CaCl2, GdmCl, NaBr, NaClO4, NaH2PO4,
      Na2SO4) on the stability of the ubiquitin molecule at pH 2.0 have been studied by
      differential scanning calorimetry, circular dichroism, and Tyr fluorescence
      spectroscopies. It is shown that all of the salts studied significantly increase
      the thermostability of the ubiquitin molecule, and that this stabilization can be
      interpreted in terms of anion binding. Estimated thermodynamic parameters of
      binding for Cl- show that this binding is relatively weak (Kd = 0.15 M) and is
      characterized by a negative enthalpy of -15 kJ/mol per site. Particularly
      surprising was the observed stabilizing effect of GdmCl through the entire
      concentration range studied (0.01-2 M), however, to a lesser extent than
      stabilization by NaCl. This stabilizing effect of GdmCl appears to arise from the
      binding of Cl- ions. Analysis of the observed changes in the stability of the
      ubiquitin molecule in the presence of GdmCl can be adequately described by
      combining the thermodynamic model of denaturant binding with Cl- binding effects.

PMID- 9541402
TI  - Serial increase in the thermal stability of 3-isopropylmalate dehydrogenase from
      Bacillus subtilis by experimental evolution.
AB  - We improved the thermal stability of 3-isopropylmalate dehydrogenase from
      Bacillus subtilis by an in vivo evolutionary technique using an extreme
      thermophile, Thermus thermophilus, as a host cell. The leuB gene encoding B.
      subtilis 3-isopropylmalate dehydrogenase was integrated into the chromosome of a
      leuB-deficient strain of T. thermophilus. The resulting transformant showed a
      leucine-autotrophy at 56 degrees C but not at 61 degrees C and above.
      Phenotypically thermostabilized strains that can grow at 61 degrees C without
      leucine were isolated from spontaneous mutants. Screening temperature was
      stepwise increased from 61 to 66 and then to 70 degrees C and mutants that showed
      a leucine-autotrophic growth at 70 degrees C were obtained. DNA sequence analyses
      of the leuB genes from the mutant strains revealed three stepwise amino acid
      replacements, threonine-308 to isoleucine, isoleucine-95 to leucine, and
      methionine-292 to isoleucine. The mutant enzymes with these amino acid
      replacements were more stable against heat treatment than the wild-type enzyme.
      Furthermore, the triple-mutant enzyme showed significantly higher specific
      activity than that of the wild-type enzyme.

PMID- 9541403
TI  - High throughput protein characterization by automated reverse-phase
      chromatography/electrospray tandem mass spectrometry.
AB  - We describe an integrated workstation for the automated, high-throughput, and
      conclusive identification of proteins by reverse-phase chromatography
      electrospray ionization tandem mass spectrometry. The instrumentation consists of
      a refrigerated autosampler, a submicrobore reverse-phase liquid chromatograph,
      and an electrospray triple quadrupole mass spectrometer. For protein
      identification, enzymatic digests of either homogeneous polypeptides or simple
      protein mixtures were generated and loaded into the autosampler. Samples were
      sequentially injected every 32 min. Ions of eluting peptides were automatically
      selected by the mass spectrometer and subjected to collision-induced
      dissociation. Following each run, the resulting tandem mass spectra were
      automatically analyzed by SEQUEST, a program that correlates uninterpreted
      peptide fragmentation patterns with amino acid sequences contained in databases.
      Protein identification was established by SEQUEST_SUMMARY a program that combines
      the SEQUEST scores of peptides originating from the same protein and ranks the
      cumulative results in a short summary. The workstation's performance was
      demonstrated by the unattended identification of 90 proteins from the yeast
      Saccharomyces cerevisiae, which were separated by high-resolution two-dimensional
      PAGE. The system was found to be very robust and identification was reliably and
      conclusively established for proteins if quantities exceeding 1-5 pmol were
      applied to the gel. The level of automation, the throughput, and the reliability
      of the results suggest that this system will be useful for the many projects that
      require the characterization of large numbers of proteins.

PMID- 9541404
TI  - Motional dynamics of residues in a beta-hairpin peptide measured by 13C-NMR
      relaxation.
AB  - Structurally characterizing partially folded peptides is problematic given the
      nature of their transient conformational states. 13C-NMR relaxation data can
      provide information on the geometry of bond rotations, motional restrictions, and
      correlated bond rotations of the backbone and side chains and, therefore, is one
      approach that is useful to assess the presence of folded structure within a
      conformational ensemble. A peptide 12mer, R1GITVNG7KTYGR12, has been shown to
      partially fold in a relatively stable beta-hairpin conformation centered at NG.
      Here, five residues, G2, V5, G7, Y10, G11, were selectively 13C-enriched, and 13C
      NMR relaxation experiments were performed to obtain auto- and cross-correlation
      motional order parameters, correlation times, bond rotation angular variances,
      and bond rotational correlation coefficients. Our results indicate that, of the
      three glycines, G7 within the hairpin beta-turn displays the most correlated
      phi(t),psi(t) rotations with its axis of rotation bisecting the angle defined by
      the H-C-H bonds. These positively correlated bond rotations give rise to
      "twisting" type motions of the HCH group. V5 and Y10 phi,psi bond rotations are
      also positively correlated, with their CbetaCalphaH groups undergoing similar
      "twisting" type motions. Motions of near-terminal residues G2 and G11 are less
      restricted and less correlated and are best described as wobbling-in-a-cone. V5
      and Y10 side-chain motions, aside from being highly restricted, were found to be
      correlated with phi,psi bond rotations. At 303 K, where the hairpin is considered
      "unfolded," the peptide exists in a transient, collapsed state because backbone
      and side-chain motions of V5, G7, and Y10 remain relatively restricted, unlike
      their counterparts in GXG-based tripeptides. These results provide unique
      information toward understanding conformational variability in the unfolded state
      of proteins, which is necessary to solve the protein folding problem.

PMID- 9541405
TI  - Multiple catalytic roles of His 287 of Rhodospirillum rubrum ribulose 1,5
      bisphosphate carboxylase/oxygenase.
AB  - Active-site His 287 of Rhodospirillum rubrum ribulose 1,5-bisphosphate (RuBP)
      carboxylase/oxygenase interacts with the C3-hydroxyl of bound substrate or
      reaction-intermediate analogue (CABP), water molecules, and ligands for the
      activator metal-ion (Andersson I, 1996, J Mol Biol 259:160-174; Taylor TC,
      Andersson I, 1997, J Mol Biol 265:432-444). To test structure-based postulates of
      catalytic functionality, His 287 was replaced with Asn or Gln. The mutants are
      not affected adversely in subunit assembly, activation (binding of Mg2+ and
      carbamylation of Lys 191), or recognition of phosphorylated ligands; they bind
      CABP with even greater tenacity than does wild-type enzyme. H287N and H287Q are
      severely impaired in catalyzing overall carboxylation (approximately 10(3)-fold
      and > 10(5)-fold, respectively) and enolization (each mutant below threshold for
      detection) of RuBP. H287N preferentially catalyzes decarboxylation of
      carboxylated reaction intermediate instead of forward processing to
      phosphoglycerate. Analysis of RuBP turnover that occurs at high concentrations of
      mutants over extended time periods reveal > 10-fold reduced CO2/O2 specificities,
      elevated misprotonation of the enediol intermediate, and misprocessing of the
      oxygenated intermediate of the oxygenase pathway. These results are consistent
      with multifaceted roles for His 287 in promoting enediol formation, enediol
      tautomerization, and forward-processing of carboxylated intermediate.

PMID- 9541406
TI  - Determinants of protein hydrogen exchange studied in equine cytochrome c.
AB  - The exchange of a large number of amide hydrogens in oxidized equine cytochrome c
      was measured by NMR and compared with structural parameters. Hydrogens known to
      exchange through local structural fluctuations and through larger unfolding
      reactions were separately considered. All hydrogens protected from exchange by
      factors greater than 10(3) are in defined H-bonds, and almost all H-bonded
      hydrogens including those at the protein surface were measured to exchange
      slowly. H-exchange rates do not correlate with H-bond strength (length) or
      crystallographic B factors. It appears that the transient structural fluctuation
      necessary to bring an exchangeable hydrogen into H-bonding contact with the H
      exchange catalyst (OH(-)-ion) involves a fairly large separation of the H-bond
      donor and acceptor, several angstroms at least, and therefore depends on the
      relative resistance to distortion of immediately neighboring structure.
      Accordingly, H-exchange by way of local fluctuational pathways tends to be very
      slow for hydrogens that are neighbored by tightly anchored structure and for
      hydrogens that are well buried. The slowing of buried hydrogens may also reflect
      the need for additional motions that allow solvent access once the protecting H
      bond is separated, although it is noteworthy that burial in a protein like
      cytochrome c does not exceed 4 angstroms. When local fluctuational pathways are
      very slow, exchange can become dominated by a different category of larger,
      cooperative, segmental unfolding reactions reaching up to global unfolding.

PMID- 9541407
TI  - Structural and functional characterization of recombinant human cellular
      retinaldehyde-binding protein.
AB  - Cellular retinaldehyde-binding protein (CRALBP) is abundant in the retinal
      pigment epithelium (RPE) and Muller cells of the retina where it is thought to
      function in retinoid metabolism and visual pigment regeneration. The protein
      carries 11-cis-retinal and/or 11-cis-retinol as endogenous ligands in the RPE and
      retina and mutations in human CRALBP that destroy retinoid binding functionality
      have been linked to autosomal recessive retinitis pigmentosa. CRALBP is also
      present in brain without endogenous retinoids, suggesting other ligands and
      physiological roles exist for the protein. Human recombinant cellular
      retinaldehyde-binding protein (rCRALBP) has been over expressed as non-fusion and
      fusion proteins in Escherichia coli from pET3a and pET19b vectors, respectively.
      The recombinant proteins typically constitute 15-20% of the soluble bacterial
      lysate protein and after purification, yield about 3-8 mg per liter of bacterial
      culture. Liquid chromatography electrospray mass spectrometry, amino acid
      analysis, and Edman degradation were used to demonstrate that rCRALBP exhibits
      the correct primary structure and mass. Circular dichroism, retinoid HPLC, UV
      visible absorption spectroscopy, and solution state 19F-NMR were used to
      characterize the secondary structure and retinoid binding properties of rCRALBP.
      Human rCRALBP appears virtually identical to bovine retinal CRALBP in terms of
      secondary structure, thermal stability, and stereoselective retinoid-binding
      properties. Ligand-dependent conformational changes appear to influence a newly
      detected difference in the bathochromic shift exhibited by bovine and human
      CRALBP when complexed with 9-cis-retinal. These recombinant preparations provide
      valid models for human CRALBP structure-function studies.

PMID- 9541408
TI  - Mass spectrometric analysis of integral membrane proteins: application to
      complete mapping of bacteriorhodopsins and rhodopsin.
AB  - Integral membrane proteins have not been readily amenable to the general methods
      developed for mass spectrometric (or internal Edman degradation) analysis of
      soluble proteins. We present here a sample preparation method and high
      performance liquid chromatography (HPLC) separation system which permits online
      HPLC-electrospray ionization mass spectrometry (ESI-MS) and -tandem mass
      spectrometry (MS/MS) analysis of cyanogen bromide cleavage fragments of integral
      membrane proteins. This method has been applied to wild type (WT)
      bacteriorhodopsin (bR), cysteine containing mutants of bR, and the prototypical G
      protein coupled receptor, rhodopsin (Rh). In the described method, the protein is
      reduced and the cysteine residues pyridylethylated prior to separating the
      protein from the membrane. Following delipidation, the pyridylethylated protein
      is cleaved with cyanogen bromide. The cleavage fragments are separated by
      reversed phase HPLC using an isopropanol/acetonitrile/aqueous TFA solvent system
      and the effluent peptides analyzed online with a Finnigan LCQ Ion Trap Mass
      Spectrometer. With the exception of single amino acid fragments and the
      glycosylated fragment of Rh, which is observable by matrix assisted laser
      desorption ionization (MALDI)-MS, this system permits analysis of the entire
      protein in a single HPLC run. This methodology will enable pursuit of chemical
      modification and crosslinking studies designed to probe the three dimensional
      structures and functional conformational changes in these proteins. The approach
      should also be generally applicable to analysis of other integral membrane
      proteins.

PMID- 9541409
TI  - Context-dependent protein stabilization by methionine-to-leucine substitution
      shown in T4 lysozyme.
AB  - The substitution of methionines with leucines within the interior of a protein is
      expected to increase stability both because of a more favorable solvent transfer
      term as well as the reduced entropic cost of holding a leucine side chain in a
      defined position. Together, these two terms are expected to contribute about 1.4
      kcal/mol to protein stability for each Met --> Leu substitution when fully
      buried. At the same time, this expected beneficial effect may be offset by steric
      factors due to differences in the shape of leucine and methionine. To investigate
      the interplay between these factors, all methionines in T4 lysozyme except at the
      amino-terminus were individually replaced with leucine. Of these mutants, M106L
      and M120L have stabilities 0.5 kcal/mol higher than wild-type T4 lysozyme, while
      M6L is significantly destabilized (-2.8 kcal/mol). M102L, described previously,
      is also destabilized (-0.9 kcal/mol). Based on this limited sample it appears
      that methionine-to-leucine substitutions can increase protein stability but only
      in a situation where the methionine side chain is fully or partially buried, yet
      allows the introduction of the leucine without concomitant steric interference.
      The variants, together with methionine-to-lysine substitutions at the same sites,
      follow the general pattern that substitutions at rigid, internal sites tend to be
      most destabilizing, whereas replacements at more solvent-exposed sites are better
      tolerated.

PMID- 9541410
TI  - Crystal structure of glycosylasparaginase from Flavobacterium meningosepticum.
AB  - The crystal structure of recombinant glycosylasparaginase from Flavobacterium
      meningosepticum has been determined at 2.32 angstroms resolution. This enzyme is
      a glycoamidase that cleaves the link between the asparagine and the N
      acetylglucosamine of N-linked oligosaccharides and plays a major role in the
      degradation of glycoproteins. The three-dimensional structure of the bacterial
      enzyme is very similar to that of the human enzyme, although it lacks the four
      disulfide bridges found in the human enzyme. The main difference is the absence
      of a small random coil domain at the end of the alpha-chain that forms part of
      the substrate binding cleft and that has a role in the stabilization of the
      tetramer of the human enzyme. The bacterial glycosylasparaginase is observed as
      an (alphabeta)2-tetramer in the crystal, despite being a dimer in solution. The
      study of the structure of the bacterial enzyme allows further evaluation of the
      effects of disease-causing mutations in the human enzyme and confirms the
      suitability of the bacterial enzyme as a model for functional analysis.

PMID- 9541411
TI  - The N-terminal segment of antithrombin acts as a steric gate for the binding of
      heparin.
AB  - The binding of heparin causes a conformational change in antithrombin to give an
      increased heparin binding affinity and activate the inhibition of thrombin and
      factor Xa. The areas of antithrombin involved in binding heparin and stabilizing
      the interaction in the high-affinity form have been partially resolved through
      the study of both recombinant and natural variants. The role of a section of the
      N-terminal segment of antithrombin, residues 22-46 (segment 22-46), in heparin
      binding was investigated using rapid kinetic analysis of the protein cleaved at
      residues 29-30 by limited proteolysis with thermolysin. The cleaved antithrombin
      had 5.5-fold lowered affinity for heparin pentasaccharide and 1.8-fold for full
      length, high-affinity heparin. It was shown that, although the initial binding of
      heparin is slightly enhanced by the cleavage, it dissociates much faster from the
      cleaved form, giving rise to the overall decrease in heparin affinity. This
      implies that the segment constituting residues 22-46 in the N terminus of
      antithrombin hinders access to the binding site for heparin, hence the increased
      initial binding for the cleaved form, whereas, when heparin is bound, segment 22
      46 is involved in the stabilization of the binding interaction, as indicated by
      the increased dissociation constant. When the heparin pentasaccharide is bound to
      antithrombin prior to incubation with thermolysin, it protects the N-terminal
      cleavage site, implying that segment 22-46 moves to interact with heparin in the
      conformational change and thus stabilizes the complex.

PMID- 9541412
TI  - Tautomeric state and pKa of the phosphorylated active site histidine in the N
      terminal domain of enzyme I of the Escherichia coli phosphoenolpyruvate:sugar
      phosphotransferase system.
AB  - The phosphorylated form of the N-terminal domain of enzyme I of the
      phosphoenolpyruvate:sugar phosphotransferase system of Escherichia coli has been
      investigated by one-bond and long-range 1H-15N correlation spectroscopy. The
      active site His 189 is phosphorylated at the Nepsilon2 position and has a pKa of
      7.3, which is one pH unit higher than that of unphosphorylated His 189. Because
      the neutral form of unphosphorylated His 189 is in the Ndelta1-H tautomer, and
      its Nepsilon2 atom is solvent inaccessible and accepts a hydrogen bond from the
      hydroxyl group of Thr 168, both protonation and phosphorylation of His 189 must
      be accompanied by a change in the side-chain conformation of His 189,
      specifically from a chi(2) angle in the g+ conformer in the unphosphorylated
      state to the g- conformer in the phosphorylated state.

PMID- 9541414
TI  - A golden era for understanding enzyme mechanisms.

PMID- 9541415
TI  - Role of machine perfusion preservation in kidney transplantation from non
      heartbeating donors.
AB  - The shortage of kidneys for transplantation is a universal problem. If the
      viability of the kidney can be assured, organ procurement from non-heartbeating
      donors will be greatly enhanced. This study evaluates the usefulness of machine
      perfusion preservation parameters as an index of kidney graft viability. We
      report our experience with 77 non-heartbeating donor kidneys preserved with
      machine perfusion technique. Sixty-eight grafts demonstrated excellent perfusion
      (mean flow 0.79 ml/min/g) with low vascular resistance (55.4 mmHg/ml/min/g).
      Early graft function occurred in all of these kidneys. Nine kidneys demonstrated
      poor perfusion (mean flow 0.35 ml/min/g) and elevated pressures with high
      vascular resistance (132.5 mmHg/ml/min/g). Four kidneys with poor perfusion and
      elevated pressures was discarded after perfusion. The four mates of these
      discarded at our center were primarily non-functional when transplanted at
      another transplant center. All five of the poorly perfused kidneys experienced
      primary non-function. We conclude that the use of quantitative values of
      perfusion flow (> 0.4 ml/min/g) and no increased pressure pattern allow safe
      utilization of grafts from non-heartbeating donors and can predict early
      postoperative function.

PMID- 9541413
TI  - S100B(betabeta) inhibits the protein kinase C-dependent phosphorylation of a
      peptide derived from p53 in a Ca2+-dependent manner.
AB  - S100B(betabeta) is a dimeric Ca2+-binding protein that is known to inhibit the
      protein kinase C (PKC)-dependent phosphorylation of several proteins. To further
      characterize this inhibition, we synthesized peptides based on the PKC
      phosphorylation domains of p53 (residues 367-388), neuromodulin (residues 37-53),
      and the regulatory domain of PKC (residues 19-31), and tested them as substrates
      for PKC. All three peptides were shown to be good substrates for the catalytic
      domain of PKC. As for full-length p53 (Baudier J, Delphin C, Grunwald D, Khochbin
      S, Lawrence JJ. 1992. Proc Natl Acad Sci USA 89:11627-11631), S100B(betabeta)
      binds the p53 peptide and inhibits its PKC-dependent phosphorylation (IC50 = 10
      +/- 7 microM) in a Ca2+-dependent manner. Similarly, phosphorylation of the
      neuromodulin peptide and the PKC regulatory domain peptide were inhibited by
      S100B(betabeta) in the presence of Ca2+ (IC50 = 17 +/- 5 microM; IC50 = 1 +/- 0.5
      microM, respectively). At a minimum, the C-terminal EF-hand Ca2+-binding domain
      (residues 61-72) of each S100beta subunit must be saturated to inhibit
      phosphorylation of the p53 peptide as determined by comparing the Ca2+ dependence
      of inhibition ([Ca]IC50 = 29.3 +/- 17.6 microM) to the dissociation of Ca2+ from
      the C-terminal EF-hand Ca2+-binding domain of S100B(betabeta).

PMID- 9541416
TI  - Hepatitis C status of heart transplant recipients.
AB  - The records of 155 consecutive patients who underwent successful heart
      transplantation (HTx) were reviewed to document the incidence of hepatitis C
      (HCV) infection. One patient was HCV RNA positive pre-HTx, and 12 patients (8%)
      developed transient or permanent HCV positivity post-HTx. HCV RNA positivity was
      associated with biochemical features of liver injury. Liver biopsy was performed
      in 8, and demonstrated features of chronic hepatitis in all. Two patients died of
      chronic liver failure at 50 and 56 months post-HTx, respectively. Interferon
      therapy was given to three patients, two of whom converted to HCV negativity.
      This study suggests that HCV infection is more common than previously anticipated
      in HTx patients, and varies from a mild transient condition to a fatal chronic
      liver failure.

PMID- 9541417
TI  - Hyperfiltration, creatinine clearance and chronic graft loss.
AB  - Chronic graft loss (CGL) may be caused by immunological- or hyperfiltration
      mediated tissue destruction. If the hyperfiltration theory is correct, grafts
      from female donors given to heavy recipients, and having a relatively poor
      initial function, should suffer an accelerated rate of loss of function. 590
      renal transplantations surviving more than 1 yr, including 171 cases of (CGL),
      were reviewed to identify causes of CGL. No overall influence of recipient or
      donor sex was found, but female donation resulted in lower acute graft loss and
      higher CGL. Warm ischemia affected CGL marginally, but cold ischemia < 12 h
      (excluding living donors) reduced CGL (35 vs. 53% at 10 yr, p < 0.05) and delayed
      function increased CGL (38% vs. 56% p < 0.001). Patients with a high urea
      production had high CGL (43% vs. 77%, p < 0.02). No overall effect of recipient
      weight was found; however 7 patients weighing > 90 kg all had CGL within 10 yr.
      Creatinine clearance was increasingly correlated to recipient weight (r = 0.23 at
      1 yr, 0.38 at 10 yr, p < 0.001). For all years, change in creatinine clearance
      correlated with change in weight (p < 0.001). The most important factor
      predicting CGL was creatinine clearance, (> 80 ml/min: 6% at 10 yr; 20-40 ml/min
      53%). However, at any level of creatinine clearance, patients with late CGL had a
      slower loss of renal function. Rate of change of renal function was proportional
      to creatinine clearance, but only for grafts surviving > 6 yr. Creatinine
      clearance rose between 3 mths and 2 yr; this rise indicated a good prognosis, was
      related to recipient weight and weight increase, and was reduced in older donors
      and cyclosporine treated patients. For patients with low clearance (< 60 ml/min),
      the increased CGL seen in patients with previous rejection episodes could be
      explained by their consequent lower clearance, but above this level, rejection
      episodes had an independent deleterious effect. These findings are compatible
      with hyperfiltration being the major cause of CGL after 6 yr. Before this
      immunological factors dominate. Good quality grafts respond to the increased
      protein load of heavy recipients with an increased GFR. Thus at any time, graft
      GFR is a function of protein-induced hyperfiltration, immunological graft
      destruction and hyperfiltration-mediated damage. Hyperfiltration-mediated renal
      damage is not a problem if the creatinine clearance is greater than 60 ml/min.

PMID- 9541418
TI  - Urinary tract infections following renal transplantation.
AB  - The incidence of urinary tract infections (UTIs) in 363 adult renal transplant
      recipients transplanted during the period 1990-96 has been analysed. UTI occurred
      in 96 patients (26%), most frequently during the first year after
      transplantation. Female recipients had significantly more UTI than male
      recipients (49% vs. 14%, p < 0.0001). There was no difference in the incidence of
      UTI between recipients receiving pig-tail catheters as ureteral stents or not,
      the figures being 21% vs. 28%, respectively. Age had no influence on the
      incidence of UTI. In 341 patients treated with cyclosporine the incidence of UTI
      was 28%, while in 15 patients treated with FK-506 only 1 patient (7%) had a UTI
      (ns). The majority of organisms cultured were gram-negative (76%), with
      approximately 1/3 being Escherichia coli and 1/5 being Enterococcus and
      Klebsiella/Enterobacter. The bacterial spectrum was not influenced by the
      recipient's age. UTI had no effect on the number of rejections, or on graft and
      patient survival in living donor transplant recipients. No significant difference
      was found in graft and patient survival rates at 3 yr between patients who had
      UTI or no UTI.

PMID- 9541419
TI  - Serial flow cytometric analysis of T-cell surface markers can be useful in
      differential diagnosis of renal allograft dysfunction.
AB  - We examined changes in the circulating T-cell subsets and their activation to see
      if consistent changes occur following renal transplantation, during acute
      rejection episodes (ARE), cytomegalovirus (CMV) infection, and cyclosporine (CsA)
      nephrotoxicity. Serial blood samples were taken from 28 patients on standard
      triple immunosuppresion therapy. Using two-colour flow cytometric analysis, the
      percentages of CD3+, CD4+, and CD8+ T-cells were determined, and coexpression of
      CD25, HLA/DR, and CD45 isoforms used to define their activation status. During
      ARE and CMV infection, increased levels of circulating CD4+ CD25+, CD8+ HLA/DR+,
      CD4+ CD45RO+, CD8+ CD45RO+ were observed. The increased levels of CD45RO+ T-cells
      were associated with a significant decrease in the percentages of CD45RA+ of both
      CD4+ and CD8+ T-cells. No significant changes were seen during CsA
      nephrotoxicity. The pattern of marker expression seen during ARE and CMV
      infection was similar to that seen in Con-A stimulated T-lymphocytes from 22
      normal controls. We conclude that, the increase in the levels of these surface
      markers do not differentiate between lymphocyte activation indicative of
      rejection or infection, but clearly distinguish episodes of CsA nephrotoxicity.
      These results could be useful in the differential diagnosis of renal allograft
      dysfunction.

PMID- 9541420
TI  - Itraconazole for the treatment of pulmonary aspergillosis in heart transplant
      recipients.
AB  - The objective of this study was to evaluate the effects of itraconazole as a
      first choice drug in the treatment of pulmonary aspergillosis in heart transplant
      recipients. Heart transplant recipients suffering from invasive pulmonary
      aspergillosis were included in this study. Group 1 included 4 patients treated
      with i.v. itraconazole (Janssen Pharmaceutica) 400 mg daily, as a first choice
      drug for 28 d. Itraconazole was discontinued and amphotericin-B was started
      before the 28th day if clinical or radiographic worsening was observed. Group 2
      included 3 patients treated with amphotericin-B as a first choice drug.
      Itraconazole was discontinued in all patients of Group 1 after 12-26 d of
      treatment because of radiographic worsening (n = 3) or combined clinical and
      radiographic worsening (n = 1). Subsequent treatment with amphotericin-B resulted
      in improvement of all patients. On a 5-yr follow-up period no relapse of
      aspergillosis was observed in 3 of them. The fourth patient expired from cerebral
      hemorrhage. The 3 patients of Group 2 treated with amphotericin-B showed a
      gradual improvement, and all were doing well on a 2-yr follow-up. In conclusion,
      in our study population consisted of heart transplant recipients amphotericin-B
      was superior to itraconazole in the treatment of invasive pulmonary
      aspergillosis.

PMID- 9541421
TI  - Possible involvement of Von Willebrand factor in pancreatic graft thrombosis
      after kidney-pancreas transplantation: a retrospective study.
AB  - Early postoperative graft thrombosis remains the second cause of failure in
      pancreas transplantation. Thus, the aim of this study was to compare
      retrospectively coagulation and fibrinolysis in type I diabetic recipients of
      simultaneous kidney pancreas transplants having or not experienced thrombosis of
      their pancreatic graft. From December 1990 to August 1996, 30 simultaneous kidney
      pancreas transplants were performed in 30 uremic type I diabetic patients. Acute
      thrombosis of the pancreatic graft was observed among 6 patients (group A),
      whereas 24 did not develop thrombosis (group B) although 4 died from other
      causes. The control groups were composed of kidney transplant (group C) or
      haemodialysed (group D) non-diabetic patients, type I diabetics with HbA1C < 8%
      (group E) or > or = 8% (group F) who were not in end-stage renal failure and
      kidney transplant type I diabetic patients (group G). Beginning at least 6 months
      after transplantation, we analysed hemostatic factors (fibrinogen, thrombin, and
      prothrombin times), coagulation inhibitors (proteins C and S), fibrinolysis
      (plasminogen activator inhibitor) and endothelial cell abnormalities (Von
      Willebrand factor: VWf). Micro and macrovascular complications were evaluated on
      a score ranging from 0 to 12. Hemostatic factors, coagulation inhibitors and
      fibrinolysis were similar in groups A and B whereas VWf differed significantly in
      group A (3.49 +/- 0.93 IU/ml) as compared to group B (2.04 +/- 0.92 IU/ml) (p <
      0.05). VWf was also significantly increased in group A relative to the control
      groups C, D, E, F, and G. The score of vascular complications was increased in
      groups A and B and significantly higher in group A (9 +/- 0.81 vs. 6.07 +/- 1.75)
      (p < 0.01), while a correlation (r = 0.812, p > 0.05) was observed between VWf
      levels and the severity of vascular complications. These results point out the
      possible involvement of VWf in the pathogenesis of pancreatic vein thrombosis in
      kidney-pancreas transplantation.

PMID- 9541422
TI  - Prospective multivariate analysis of donor monoethylglycine xylidide (MEGX)
      testing in liver transplantation. Transplantation Society of Michigan Scientific
      Studies Committee.
AB  - Measurement of the metabolism of lidocaine to MEGX by the hepatic cytochrome P450
      system has been proposed as a means to assess liver function and metabolic
      activity of cadaveric organ donors. This prospective study of 102 potential liver
      donors from the State of Michigan sought to determine the role of MEGX
      determinations alone and in conjunction with traditional measures of donor
      acceptability. High MEGX values (> 80 microg/L) did not correlate with the
      acceptability of donor livers, and had no significant association with early
      posttransplant graft function, as determined by SGOT, SGPT, alkaline phosphatase,
      bilirubin, prothrombin time, or bile production. However, livers procured from
      donors with high MEGX values had improved actuarial graft survival when compared
      to low MEGX donors at 30 d (95% vs. 84%) and at 1 yr (68% vs. 43%) (p < 0.04).
      Multivariate analysis demonstrated a significant independent association of both
      shorter cold ischemic time and high MEGX value with improved graft survival (p <
      0.002). We conclude that the MEGX test offers limited incremental value in
      predicting early function of donor livers when used in conjunction with
      traditional criteria of clinical evaluation, laboratory tests, and histology.
      However, knowledge of the results of MEGX determinations may be of value in
      predicting graft survival after liver transplantation.

PMID- 9541423
TI  - Direct measurement of graft and recipient liver fossa size by computed tomography
      for avoiding problems due [correction of clue] to large graft size in living
      related liver transplantation.
AB  - We investigated the incidence and manifestation of problems associated with large
      graft size in living-related liver transplantations and assessed the usefulness
      of determining volume and dimensions of the graft and recipient's liver fossa by
      computed tomography to indicate the risk. Five of 150 living related liver
      transplantations had grafts that were too large, resulting in difficulty in
      primary abdominal closure or in sudden worsening of hemodynamics during primary
      closure. No significant difference existed in recipient age, sex, body weight,
      selection of the graft segment, hepatic vein reconstruction, recipient resected
      liver weight, graft volumetry value, the ratio of body weight of donor relative
      to recipient, and the percentage of graft weight relative to recipient body
      weight, between the groups with and without these problems. Mean +/- SEM of
      maximal dimensional ratio, defined as the maximum of the ratios of 3 dimensions
      of the graft relative to recipient liver fossa, were 2.36 +/- 0.64 for patients
      with grafts that were too large and 1.00 +/- 0.02 for the cases without size
      problems. The mean +/- SEM of liver fossa index, defined as the product of 3
      dimensions of recipient liver fossa, were (25.03 +/- 7.18) x 10(4) mm3 and
      (127.54 +/- 5.07) x 10(4) mm3, respectively. These two indices clearly indicated
      the risk of problems due to large graft size, and will help to protect recipients
      and provide a basis for evaluating graft size in reductions.

PMID- 9541424
TI  - Use of glucose disappearance rates (kG) to monitor endocrine function of pancreas
      allografts.
AB  - We have reported that a decline in glucose disappearance rate (kG) in pancreas
      transplant recipients is associated with pancreatic rejection. The purpose of
      this study was to determine test-retest reliability of kG monitoring and to
      establish the kG criteria for diagnosing abnormal graft function. Six healthy non
      diabetic volunteers and 14 stable pancreas recipients underwent 2 intravenous
      glucose tolerance tests 7 d apart. All kG values in non-diabetic volunteers had <
      15% variation between the two determinations (r = 0.96, P < or = 0.0006).
      Similarly, 13/14 recipients experienced < 20% variation in kG with one patients
      experiencing a 23% variation (r = 0.90, P < or = 0.0001). Using a 20% change from
      baseline as the reference value, we monitored 28 pancreas recipients for 2-36
      months post-transplant. Of 253 kG values, 160 (64%) did not exceed the 20% change
      from baseline, 65 (26%) declined > 20% and 28 (11%) increased > 20%. Of 160
      stable kG values, 154 (96%) were associated with normal graft function while 6
      (4%) occurred in the context of rejection. Of 65 kG values declining by > or =
      20%, 47 (72%) accurately identified acute rejections diagnosed by biopsy (70%) or
      response to treatment (30%), 12 (19%) were associated with identifiable causes of
      increased insulin resistance and only in 6 (9%) cases a cause for the decline was
      unidentifiable. The kG values with > 20% rise from baseline were, in 15%,
      associated with identifiable causes of decreased insulin resistance. The
      sensitivity of the kG as a marker for rejection was 88.7%, specificity 91%,
      positive predictive value 72.3%, negative predictive value 96.8%, and accuracy
      90.5%. These data confirm that a > 20% deterioration of glucose disappearance
      rate is associated with pancreas allograft rejection, and confirms the utility of
      kG monitoring in clinical follow-up of pancreas transplant recipients.

PMID- 9541425
TI  - Carcinoma of the bladder in renal transplant patients. A case report and
      collective review of cases.
AB  - Bladder malignancy in the renal transplant recipient is an infrequent occurrence.
      The 11 previously reported cases reflect an aggressive tumor growth with
      invasion, requiring partial or complete cystectomy with or without conduit
      diversion. We report an additional case in a 40-yr-old woman with a living
      related renal transplant, who experienced rapid progression of her tumor over 3
      wk from initial hematuria to a pelvic mass involving the anterior bladder. Her
      allograft ureter and native ureters, as well as her left iliac vein, became
      obstructed with tumor in another 2 wk. Biopsy showed poorly differentiated,
      invasive transitional carcinoma. Attempted resection was abandoned because of
      finding tumor involvement in most of the pelvis. Chemotherapy was not attempted.
      She died 2 wk after her attempted resection from tumor burden. Our report
      presents a collective review of these previously reported 11 cases plus our case.
      These bladder tumors demonstrate a rapid progression of invasive disease and
      respond poorly to chemotherapy. There is a possible association of bladder tumors
      with cyclophosphamide immunosuppression. An aggressive surgical approach should
      be followed, especially since these tumors present in a younger age group.

PMID- 9541426
TI  - A new anastomotic technique in renal transplants reduces warm ischemia time.
AB  - The cause of allograft dysfunction following renal transplantation has not yet
      been fully determined. However, one of the principal factors known to cause
      dysfunction in renal transplantation is warm ischemia. A new vascular anastomosis
      technique that reduces anastomotic time and the amount of warm ischemia time
      during the implantation phase was tested. A retrospective review compared 21
      consecutive sutureless renal transplants with 31 consecutive suture transplants
      using a new technique performed by the same surgeon in the previous 12 months.
      The results showed the warm ischemia time was reduced by 51% (from 42.4 min to
      24.04 min) with the new anastomotic technique, and with few complications.
      Initial experience with the new anastomotic technique is favorable. Further
      experience is needed to fully evaluate the complications and long-term outcomes
      using this technique.

PMID- 9541427
TI  - The genotype-phenotype controversy in ophthalmology. Implications of
      heterogeneity on diagnosis, embryology and molecular function.
AB  - Genetic heterogeneity in ophthalmology adds a new dimension to differential
      diagnosis and prognosis. The indispensable clinical classification is refined by
      molecular genetic strategies. They sometimes build up new families of diseases,
      sometimes indicate that what was thought to be aetiologically related disorders
      are caused by different genetic mechanisms. Heterogeneity throws new light on
      embryological pathways, and the molecular genetics of the eye increases the
      information of the localisation of metabolically active substances and structural
      proteins in the eye.

PMID- 9541429
TI  - Detection of mitochondrial DNA nucleotide 11778 point mutation of Leber
      hereditary optic neuropathy from archival stained histopathological preparations.
AB  - PURPOSE: We evaluated the availability of archival histopathological preparations
      for genetic diagnosis of Leber hereditary optic neuropathy (LHON). METHODS:
      Preparations of various tissues of an autopsied case of LHON, and of the
      optochiasmal arachnoidea of nine cases of bilateral optic neuropathy (BON) were
      studied to determine the presence of a point mutation of the mitochondrial DNA
      nucleotide (nt) 11778 using PCR method. RESULTS: An nt11778 point mutation was
      detected in all preparations of the autopsied case. Five preparations out of six
      BON cases who were diagnosed as LHON based on positive family history, revealed
      this point mutation. This mutation was also detected in two of three BON patients
      with no family history of the disease. CONCLUSION: The archival preparations were
      found to be available as materials of genetic diagnosis for LHON, which indicated
      that it would be capable to reevaluate retrospectively the pedigree of LHON and
      BON cases.

PMID- 9541428
TI  - Retinal manifestations in mitochondrial diseases associated with mitochondrial
      DNA mutation.
AB  - PURPOSE: To scrutinize retinal involvement associated with distinct mitochondrial
      DNA (mtDNA) defects, we reviewed the records of a consecutive series of patients
      with various mitochondrial diseases. METHODS: Clinical, laboratory and mtDNA
      studies were performed in: five patients with Kearns-Sayre syndrome (KSS); six
      patients with chronic progressive external ophthalmoplegia (CPEO); three patients
      with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like
      episode (MELAS); three patients with myoclonic epilepsy and ragged-red fibers
      (MERRF); 20 patients with Leber's hereditary optic neuropathy (LHON); 30 patients
      with simple diabetes mellitus. RESULTS: All KSS patients with neurologic and
      cardiac symptoms associated with a deletion of mtDNA in muscle biopsy specimens
      showed widespread retinal pigmentary changes characterized by salt- and pepper
      like appearance of the fundus. Three of six patients with CPEO, a mild variant of
      KSS, showed subtle defects at the level of retinal pigment epithelium of the
      posterior pole, although mtDNA deletion was similar to that in KSS. Of three
      patients with MELAS syndrome, one patient showed juvenile cataract and mild
      retinal pigmentary defect in the posterior pole. Of three patients with MERRF
      syndrome associated with a mtDNA mutation at nucleotide position (np) 8344, one
      patient showed mild pigment disorder in the posterior pole in addition to optic
      neuropathy. Two of 20 patients with LHON associated with a mtDNA mutation at np
      11778 showed mild pigmentary defect in the macula together with typical optic
      neuropathy. In addition, two of 30 patients with isolated diabetes mellitus
      showed a mtDNA mutation at np 3243 (MELAS mutation), but they did not present
      with any other neurologic or multisystem disorder. CONCLUSION: The retina, in
      particular the retinal pigment epithelium, is highly vulnerable to be involved by
      mtDNA defect, and the retinopathy is phenotypically variable and frequently
      subclinical, depending to some extent on the type or site of mtDNA defect.

PMID- 9541430
TI  - Congenital ectopia lentis. A Danish national survey.
AB  - PURPOSE: To elucidate demographic and nosologic characteristics of congenital
      ectopia lentis (ECL) in Denmark. METHODS: A register of affected persons was
      established based on information provided from medical records and files in a
      nation-wide retrospective study, the Danish ECL-study. RESULTS: Three hundred and
      ninety-six cases (197 males, 199 females) with ECL were included in the study. By
      January 1st, 1993, the estimated prevalence rate of ECL was 6.4/100,000. The
      estimated average point prevalence rate at birth 1976-85 was 0.83/10,000 live
      born. Only in 69% of the cases (274/396) was a nosologic classification possible,
      based on preexisting information about familial occurrence, systemic and ocular
      findings: Marfan syndrome was found in 68.2% of these (187/274), ectopia lentis
      et pupillae in 21.2%, simple dominant ectopia lentis in 8.0%, homocystinuria in
      1.1%, sulfite oxidase deficiency and Weill-Marchesani syndrome in 0.7% each. In
      the remaining 31% (122/396) a nosologic diagnosis could not be established.
      CONCLUSION: The majority of affected persons have congenital ectopia lentis as a
      manifestation of a systemic disease. It is therefore essential to evaluate ECL
      patients systemically with a general physical examination, a metabolic screening,
      and an echocardiography as a minimum, in order to make a nosologic diagnosis and
      to prevent potentially life-threatening systemic complications.

PMID- 9541431
TI  - Treatment of strabismus and nystagmus with botulinum toxin type A. An evaluation
      of effects and complications.
AB  - PURPOSE: Injection of botulinum toxin type A into eye muscles leads to a
      temporary paralysis and the effects have been evaluated in strabismus or
      nystagmus. METHOD: A total of 112 patients with different types of concomitant
      and paralytic strabismus and acquired nystagmus were treated with botulinum
      toxin, according to well-established indications. RESULTS: The lasting effects of
      the injections on strabismic angle were largest in esotropia, consecutive
      exotropia and abducens palsy, and amounted to, on an average, 12 prism diopters
      or 6 degrees. The larger the strabismus the better was the effect. Repeated
      injections reduced the angle further. In complex nystagmus forms retrobulbar
      injections could be used. The side effects were mostly due to spread of botulinum
      toxin to the levator, producing ptosis (8%), or the inferior rectus muscle,
      causing vertical strabismus (10%). On an average 42% of the patients were later
      operated for strabismus and nystagmus. CONCLUSION: Injection of botulinum toxin A
      into eye muscles is a valuable adjunct to surgery in the treatment of strabismus
      and nystagmus.

PMID- 9541432
TI  - The relation between visual acuity and the size of fixational eye movements in
      patients with diabetic and non-diabetic macular disease.
AB  - PURPOSE: To study fixational eye movements as a function of visual acuity (VA) in
      patients with diabetic maculopathy and in patients with non-diabetic macular
      disease. MATERIAL: Two groups of patients each with VA ranging between 0.05-0.77
      were studied, i.e. 24 patients with diabetic maculopathy and 23 patients with non
      diabetic macular lesions. Fixational eye movements were quantified from video
      recordings of the ocular fundus obtained with the Rodenstock scanning laser
      ophthalmoscope. RESULTS: Within both groups of patients we found a similar
      significantly negative relation between the amplitude of fast saccadic eye
      movements and the VA. Patients with VA > 0.20 showed a normal directional pattern
      with larger amplitudes of the fast saccadic movements in the horizontal than in
      the vertical plane, whereas for patients with VA < or = 0.20 the amplitudes of
      the saccadic movements in the vertical plane had enlarged to equal the saccadic
      amplitude in the horizontal plane. Four patients with VA < or = 0.10 had the
      fixation centre located more than three degrees (approximately 500 microns at the
      retinal plane) from the centre of the foveal avascular zone, whereas the fixation
      centre of the remaining 43 patients was within one degree of the centre of this
      zone. CONCLUSION: Patients with VA < or = 0.20 may have retinal areas of fixation
      located more than 500 microns from the fovea. This fact should be taken into
      account when planning retinal photocoagulation in macular disease.

PMID- 9541433
TI  - The acute effect of topical beta-adrenoreceptor blocking agents on retinal and
      optic nerve head circulation.
AB  - PURPOSE: Topical beta-blockers are the most common treatment for ocular
      hypertension in glaucoma, but their ocular hemodynamic effects are not well
      known. We investigated the acute effects of betaxolol (beta-1 selective
      antagonist), levobunolol (non-selective antagonist with active polar metabolite),
      and timolol (non-selective antagonist) on retinal and superficial optic nerve
      head circulation. METHODS: Intraocular pressure (IOP), heart rate, blood
      pressure, and retinal circulation were evaluated in 12 healthy subjects (6F/6M;
      mean age=24+/-2 years) before and two hours after instillation of each drug on
      separate occasions at least two weeks apart. Macular capillary blood velocity
      (MCBV), epipapillary blood velocities (EBV), arteriovenous passage (AVP) times,
      and arterial and venous diameters were measured by digital image analysis of
      scanning laser fluorescein angiograms. RESULTS: All drugs significantly (p<0.05)
      reduced IOP. There was no significant effect on blood pressure or calculated
      ocular perfusion pressure. Only levobunolol significantly lowered heart rate
      (p<0.05). Each drug produced a significant (p<0.01) decrease in AVP time of
      approximately 25%. MCBV was significantly (p<0.01) increased by approximately 20%
      in all three conditions; each drug also produced significant (p<0.01) increases
      in EBV. Arterial and venous diameters remained unaffected. CONCLUSION: All three
      drugs, despite different beta-adrenergic properties, increased blood velocities
      in retinal and epipapillary capillaries. These changes, occurring as they do in
      concert with decreased retinal arteriovenous passage time at constant retinal
      arterial and venous diameter, may indicate improved retinal perfusion after drug
      treatment. Improved circulation, if it indeed occurs, in tandem with reduced IOP,
      might explain in part the beneficial effect of beta-adrenoreceptor blocking
      agents in glaucomatous patients.

PMID- 9541434
TI  - Visual Ability Score -- a new method to analyze ability in visually impaired
      children.
AB  - PURPOSE: We analyzed the correlation between the Preferential Looking (PL)
      acuities and the Visual Ability Scores (VAS) of 600 patients (many with severe
      retinopathy of prematurity) to determine their ability to perform various
      activities within the daily environment. METHODS: Visual acuity was measured by
      PL. Sixteen visual activities within the environment were analyzed. The VAS
      (range, 1-16) were calculated from the results of each activity and correlated
      with PL acuity. RESULTS: The PL acuities of the 600 patients ranged from 20/20
      (1.0) to <20/3200 (0.006) [mean, 20/337(006)]. The VAS ranged from 1 to 16 points
      (mean, 10.65; SD, +/-4.80) and showed a high correlation with the PL acuities
      (r=0.917, p=0.0001). CONCLUSIONS: In addition to PL vision testing, analyzing the
      environmental visual behavior of young, severely visually impaired patients is
      important to accurately evaluate visual abilities. We found the VAS to be an
      important aid for low-vision specialists, especially for those with no access to
      a vision evaluation system such as PL.

PMID- 9541435
TI  - Clinical study of [123I] N-(2-diethylaminoethyl)-4-iodobenzamide in the diagnosis
      of primary and metastatic ocular melanoma.
AB  - PURPOSE: To assess the value of scintigraphy with [123I]N-(2-diethylaminoethyl)-4
      iodobenzamide (BZA), a phase II clinical trial was performed on 48 patients with
      a suspicion of ocular melanoma. METHODS: 56 examinations were performed to image
      lesions with a clinical diagnosis of primary ocular melanoma before and/or after
      treatment, to observe the results in simulating lesions or to image metastases.
      RESULTS: Ocular BZA-scintigraphy demonstrated a sensitivity of 86%, and a
      specificity of 83%. Whole-body scintigraphy was used in the follow-up of treated
      patients and could be repeated. We imaged orbital recurrence, known and occult
      metastases, specially in the liver. After 9 conservative treatments ocular BZA
      scintigraphy was negative in 9 eyes. CONCLUSION: The BZA-scintigraphy in
      combination with other diagnostic procedures appeared to be a suitable method in
      the diagnosis of ocular melanoma and a potentially useful imaging modality to
      screen for ocular malignant melanoma metastases.

PMID- 9541436
TI  - Whole blood selenium in exudative age-related maculopathy.
AB  - PURPOSE: We tested whether exudative ARM was associated with low whole blood
      levels of selenium (Se). METHODS: Blood samples, drawn from 10 exudative ARM
      patients (61.2-76.1 yr) and 9 healthy-eyed (66.9-75.1 yr) subjects, were analyzed
      by atomic absorption spectroscopy. RESULTS: Selenium concentration was
      significantly lower in the ARM group (186.6 microg/l) than in controls (207.0
      microg/l). Because many ARM patients took Se supplements, we tested the effect on
      blood Se of 80 microg per day of sodium selenate. We found no enduring effects of
      supplementation for healthy-eyed, younger adults. CONCLUSIONS: Significant group
      differences in this preliminary study indicate a larger-scale study of blood Se
      concentration in exudative ARM patients is warranted. If the effect of Se
      supplementation on the progression of exudative ARM is tested in future trials,
      it will be important to use organic Se, to identify the components of blood
      affected, and to observe protocol for at least six months.

PMID- 9541437
TI  - Retinal vascular changes following supplementation with alpha-tocopherol or beta
      carotene.
AB  - PURPOSE: To examine if long-term supplementation with alpha-tocopherol (AT) or
      beta-carotene (BC) was associated with the prevalence of vascular changes in
      retinal arterioles. METHODS: An end-of-trial subsample from a double-blind,
      placebo-controlled clinical trial designed to study the effects of alpha
      tocopherol and beta-carotene on lung cancer incidence (ATBC Study). SETTING:
      Source population of Helsinki and the surrounding province. PARTICIPANTS: 1072
      men 50-69 years old and smoking at least 5 cigarettes per day at study entry.
      INTERVENTIONS: Random allocation to one of four supplementation regimens: 50 mg
      per day alpha-tocopherol, 20 mg per day beta-carotene, both alpha-tocopherol and
      beta-carotene, or placebo. Median follow-up time was 6.6 years (range 5.2-8.0
      years). MAIN OUTCOME MEASURE: Presence of vascular changes in retinal arterioles
      as determined from end-of-trial retinal color photographs. RESULTS: Retinal
      vascular changes were most prevalent in the AT (161 men, 62%), and in the BC (163
      men, 62%) groups. The prevalence rate was lowest in the AT plus BC group (161
      men, 55%), and slightly higher in the placebo group (145 men, 57%). There was no
      statistically significant association of either AT (OR 0.9, 95% CI 0.7-1.2) or BC
      (OR 1.0, 95% CI 0.8-1.3) supplementation with the prevalence of retinal vascular
      changes after adjusting for major risk factors. CONCLUSIONS: Supplementation with
      alpha-tocopherol or beta-carotene for a median of 6.6 years does not protect
      against retinal vascular changes among smoking males.

PMID- 9541438
TI  - Ocular surface and environmental changes.
AB  - PURPOSE: To investigate if ocular surface and precorneal tear film are influenced
      by the environment. METHOD: We studied the environmental influences on the ocular
      surface using the tests Break-up time, Schirmer-1 test and Rose Bengal staining.
      We correlated the values of the above tests among three groups of normal people
      from different places in Greece with different climates and levels of atmospheric
      pollution. Group A consisted of 57 persons coming from an area with a dry and
      warm climate and heavy atmospheric pollution. Group B consisted of 55 normal
      persons coming from an area with a dry and warm climate and a low level of
      atmospheric pollution. Group C consisted of 55 persons coming from an area with a
      humid and cool climate and a low level of atmospheric pollution. RESULTS:
      Schirmer-1 test and Break-up time are influenced by the climatic conditions but
      they are not influenced by the atmospheric pollution, while Rose Bengal staining
      is not influenced either by the climate or by the atmospheric pollution.
      CONCLUSION: The precorneal tear film is much more influenced by the climatic
      conditions than by the atmospheric pollution.

PMID- 9541439
TI  - Influence of dorzolamide on corneal thickness, endothelial cell count and corneal
      sensibility.
AB  - PURPOSE: Dorzolamide (Trusopt) is the first topical carbonic anhydrase inhibitor
      (CAI) that is in clinical use in glaucoma therapy. It is known that CAI have a
      negative effect on corneal endothelial pumpfunction and therefore on the whole
      corneal physiology. METHODS: 20 patients with open angle glaucoma or ocular
      hypertension and an elevated intraocular pressure (IOP) over 21 mmHg and without
      prior oral CAI-treatment were included in this study. Trusopt was administered
      t.i.d. as monotherapy and b.i.d. in combination with other topical antiglaucoma
      drugs. Corneal ultrasound pachymetry, corneal endothelial cell count and
      aesthesiometry were performed prestudy and on days 1, 8, 15, 30, 60 and 90.
      RESULTS AND CONCLUSIONS: Mean corneal thickness was slightly increased on day one
      (statistically non-significant) and returned to baseline measurements at the
      following visits, no changes in endothelial cell count and corneal anesthesia
      were found. Topical dorzolamide is not associated with clinically meaningful
      changes of the cornea.

PMID- 9541440
TI  - Intraoperative mitomycin C and the corneal endothelium.
AB  - PURPOSE: Mitomycin-C (MMC) is a useful adjunct to high risk glaucoma surgery. No
      clinical data regarding the deleterious effect of mitomycin-C on the corneal
      endothelial cells are available. METHODS: Thirty eyes of 28 adult patients with
      high risk glaucomas were randomized to three groups. Group-I underwent a
      trabeculectomy alone, Group II, trabeculectomy with intraoperative 0.2mg/ml MMC
      and Group III, trabeculectomy with intraoperative 0.4mg/ml MMC. Preoperative and
      3-month postoperative corneal endothelial cell counts were analysed. RESULTS: The
      percentage cell loss in Group I was 3.73+/-2.73%, in Group II 13.90+/-4.69% and
      in Group III 14.52+/-7.8%. Statistical analysis revealed a significant difference
      in cell loss between Group I and Group II and Group I and Group III, but not
      between Group II and Group III. CONCLUSION: There is a significant loss of
      corneal endothelial cells three months after trabeculectomy with adjunctive MMC.

PMID- 9541441
TI  - Modification of trabeculectomy with single-dose intraoperative 5-Fluorouracil
      application.
AB  - PURPOSE: To assess the outcome of trabeculectomy supplemented with intraoperative
      5-Fluorouracil (5 FU) application in glaucoma patients. METHODS: A prospective
      non-randomized case series of 76 eyes of 76 consecutive patients who underwent
      trabeculectomy with intraoperative sponge 5 FU (25 mg/ml). Minimum follow-up was
      6 months. There were 31 eyes in the low-risk group and 45 eyes in the high-risk
      group. The reduction in intraocular pressure (IOP) and any treatment
      complications were noted. RESULTS: The mean preoperative IOP was 28+/-7.72 mm Hg.
      The mean final postoperative IOP was 16.8+/-6.1 mm Hg. The average number of
      glaucoma medications required dropped from 1.8+/-0.8 preoperatively to 0.4+/-0.8
      after the operation (p<0.001). Cumulative success rates (IOP less than 21 mm Hg)
      for all eyes were 93% and 81% at 6 and 12 months, respectively. There was no
      difference in outcome between the low- and high-risk groups if criteria for
      success were an IOP of less than 21 mm Hg or an IOP of less than 21 mm Hg and an
      IOP reduction of 30%. However, if success is defined as an IOP of 15 mm Hg or
      less and a 30% fall in IOP, then the low-risk group had significantly longer
      survival times than the high-risk group (p=0.033, log-rank test). Transient
      punctate keratitis and corneal epithelial defect were each observed in only 1
      eye. Other serious complications include rapid progression of cataract in 2 eyes,
      endophthalmitis in 1 eye and hypotonic maculopathy after subsequent cataract
      extraction in 1 eye. CONCLUSION: Single dose intraoperative 5 FU appears to be a
      safe and useful adjunct to trabeculectomy. IOPs in the low teens were achieved in
      a greater proportion of low-risk eyes than high-risk eyes.

PMID- 9541442
TI  - The relationship between the types of axial elongation and the prevalence of
      lattice degeneration of the retina.
AB  - PURPOSE: To assess the relationship between the prevalence of lattice
      degeneration and the types of axial elongation. METHODS: Nine hundred seventy
      eyes of 542 highly myopic patients with axial length of 26.00-31.99 mm were
      evaluated by using A-scan axial length measurements and fundus examinations. Then
      the prevalence of lattice degeneration was compared between eyes with posterior
      staphyloma and those without posterior staphyloma. RESULTS: At each axial length,
      lattice degeneration was more frequent in eyes without posterior staphyloma (the
      entire eye elongates) than those with posterior staphyloma (only the posterior
      pole elongates). The difference was statistically significant (p<0.005-0.05).
      CONCLUSION: The prevalence of lattice degeneration is influenced by the types of
      axial elongation in high myopic eyes.

PMID- 9541443
TI  - Cyclosporin-A therapy in severe uveitis of Behcet's disease.
AB  - PURPOSE: Cyclosporine-A (CSA) combined with corticosteroid therapy was
      administered to 12 patients with severe Behcet's uveitis who were resistant to
      colchicine or cytotoxic therapy. METHODS: Previous colchicine or cytotoxic
      therapies were tapered off one month before CSA therapy. All patients were
      started on an initial oral dose of 5 mg/kg/day of CSA. After the first three
      months, the CSA dose was reduced to a maintenance dose according to the
      intraocular inflammatory response. RESULTS: The average follow-up period was 20
      (12-36) months. Visual acuity remained the same in 12 (%54.5) and improved in 8
      (%36.4) eyes. There was a decrease in the frequency (p<0.01) and severity
      (p<0.01) of ocular attacks and in the maintenance steroid dose (p<0.01) when
      compared with conventional therapy. The frequent side effects were paraesthesia
      hyperesthesia, fatigue, nausea, hirsutism and dose-related nephrotoxicity in one
      patient. CONCLUSION: The results of the study suggest that low dose CSA combined
      with low dose corticosteroid may be an effective therapeutic alternative in the
      treatment of severe refractory Behcet's uveitis.

PMID- 9541444
TI  - Ophthalmic findings of newly diagnosed leprosy patients in Istanbul Leprosy
      Hospital, Turkey.
AB  - The objective of this study was to detect ocular lesions of newly diagnosed
      leprosy cases admitted to Istanbul Leprosy Hospital. The patients were
      categorized according to sex, age, type of leprosy and duration of the disease.
      Their eyes were categorized as with or without ocular findings due to leprosy.
      The total number of patients was 21. The mean age was 22+/-4.6 years, the
      duration of the disease was 36.3+/-19.6 months. Madarosis was the most common
      finding in this group. It was found in 15 patients (71.4%, 95% confidence
      interval (CI) 47.8-88.7%). As a second common finding related to corneal
      alterations, 13 patients had nerve thickening (61.9%, 95% CI 38.4-81.8%). None of
      our patients had trichiasis, episcleritis, scleritis, cataract, iris atrophy,
      iris pearl, abnormal vitreous or retinal findings.

PMID- 9541445
TI  - Enucleation and evisceration in Iceland 1964-1992. Study in a defined population.
AB  - A retrospective study showed that from 1963-1992 200 eyes were enucleated or
      eviscerated in Iceland. The mean annual age-adjusted incidence per 100,000
      population was 2.66, 50% higher for males than females. The mean annual age- and
      gender-adjusted incidence has decreased; was highest 3.58 per 100,000 for the
      period 1971-1978, but was 1.76 per 100,000 for the period 1985-1991. The
      indications were 1) Blind painful eye (92 eyes), 2) Suspicion of malignant
      neoplasm (49 eyes), 3) Acute trauma (35 eyes), 4) Corneal ulcer (17 eyes), 5)
      Other (7 eyes). Of blind painful eyes only 12 (6%) were due to neovascular
      glaucoma. Medical care is self-contained within the country, the incidence for
      enucleation is decreasing for all categories except malignancy.

PMID- 9541446
TI  - Comparison of Fucithalmic viscous eye drops and Chloramphenicol eye ointment as a
      single treatment in corneal abrasion.
AB  - PURPOSE: To compare the healing of the cornea and the incidence of infection
      after traumatic corneal epithelial defect after single treatment with double
      bandage combined with either Fucithalmic single unit dose eye drops or
      chloramphenicol eye ointment. METHODS: This is a single-centre, randomised,
      single-blind, parallel-group study of 144 patients with accidental corneal
      abrasion or corpus alieni cornea who were referred to the Eye Department at
      Gentofte Hospital. The injured eye was examined with a photo slit-lamp before and
      24 hours after treatment. The size of the abrasion was recorded and calculated on
      a PCX computerized video system and by slit-lamp photography. RESULTS &
      CONCLUSION: The Fucithalmic and chloramphenicol ointment treated groups showed no
      significant difference in corneal healing, local side effects, or signs of local
      infection.

PMID- 9541447
TI  - Congenital glaucoma associated with Rubinstein-Taybi syndrome.
AB  - PURPOSE/METHODS: Rubinstein-Taybi syndrome is a constellation of clinical
      findings characterized by mental and motor retardation, broad thumbs and broad
      first toes, marked growth retardation, microcrania, typical facies, high-arched
      palate, and cryptorchidism in males. Ocular and adnexal abnormalities are quite
      common and include antimongoloid slant of the palpebral fissures, epicanthal
      folds, congenital obstruction of the lacrimal excretory system, ptosis,
      strabismus, and severe ametropia. Macrocornea, microophthalmos, colobomas of the
      iris and of the optic nerve head, congenital cataract, and optic nerve atrophy
      have also been described. Congenital glaucoma is a rare complication. We examined
      a patient with Rubinstein-Taybi syndrome with bilateral congenital glaucoma.
      RESULTS/CONCLUSIONS: Examination of this patient revealed bilateral antimongoloid
      slants of the palpebral fissures, and bilateral congenital glaucoma. Gonioscopic
      examination revealed the iris to be inserted flatly into the trabecular meshwork.
      This case emphasizes the importance of detailed, complete ocular examinations in
      patients with Rubinstein-Taybi syndrome, and also highlights the occurrence of
      ocular abnormalities rarely associated with this disease.

PMID- 9541448
TI  - Multiple endocrine neoplasia 2B with glaucoma associated with codon 918 mutation
      of the RET proto-oncogene.
AB  - PURPOSE: We report the first case of a 35-year-old Japanese man with multiple
      endocrine neoplasia (MEN) 2B de novo to be associated with primary open angle
      glaucoma. METHODS: DNA was extracted from the patient's circulating leukocytes,
      specimens of the resected cervical lymph nodes, the neuroma of the eyelid, and of
      the conjunctival epithelium. Mutation was assayed by PCR/restriction enzyme and
      direct sequencing. RESULTS: The glaucoma and MEN 2B were diagnosed at the same
      time, when the patient was 16 years old. The glaucoma was controlled by medical
      treatment. The codon 918 mutation (met918thr) in exon 16 of the RET proto
      oncogene associated with MEN 2B was identified in all these tissues. CONCLUSION:
      This patient was found to have the germline mutation at codon 918 (met918thr) in
      the RET proto-oncogene. The association between the RET proto-oncogene and
      glaucoma remains unclear, since glaucoma is a rare manifestation of MEN 2B.

PMID- 9541449
TI  - Limbal autograft transplantation.

PMID- 9541450
TI  - Idiopathic intracranial hypertension presenting with gaze-evoked amaurosis.
AB  - PURPOSE: Gaze-evoked amaurosis is transient monocular visual loss induced by an
      eccentric position of gaze, most frequently associated with orbital mass lesions.
      To our knowledge, there has been no reported case of idiopathic intracranial
      hypertension as a cause of gaze-evoked amaurosis. We present the hypothesis that
      in an eccentric position of gaze, ischaemic compression of a tense dilated optic
      nerve sheath results in further elevation of intrasheath pressure compromising
      blood flow to the retina. METHOD: We describe a case of unilateral gaze-evoked
      amaurosis and headaches in a 46 year old man diagnosed with idiopathic
      intracranial hypertension. He did not respond to medical treatment and had optic
      nerve sheath decompressions. RESULT: Following surgery, this patient's visual
      function improved with resolution of his gaze-evoked amaurosis. CONCLUSION:
      Raised intracranial pressure associated with a tense dilated optic nerve sheath
      should be considered in the differential diagnosis of gaze-evoked amaurosis.

PMID- 9541451
TI  - Endogenous endophthalmitis caused by Rickettsia conorii.
AB  - PURPOSE: We report herein the first confirmed case of endogenous endophthalmitis
      caused by Rickettsia conorii. METHODS: Indirect immunofluorescence was performed
      in peripheral blood with antibodies against Rickettsia conorii. A vitreous
      aspirate was studied by indirect immunofluorescence with antibodies against
      Rickettsia conorii and by direct immunofluorescence with conjugated antigen
      against Rickettsia conorii. RESULTS: Indirect immunofluorescence in peripheral
      blood gave a titre of 1/320 at that moment and 1/640 fifteen days later. The
      vitreous aspirate studied by indirect immunofluorescence gave a titre of 1/620
      and it showed a positive reaction to Rickettsia conorii antigen by direct
      immunofluorescence. CONCLUSION: Rickettsia conorii should be considered in the
      differential diagnosis of endogenous endophthalmitis in areas where Mediterranean
      spotted fever is endemic.

PMID- 9541452
TI  - Entamoeba infected orbital cysts as a late complication to orbital floor
      fractures.
AB  - An unusual late complication to an orbital floor fracture is presented. Five
      years after trauma a now 22-year old man demonstrated an entamoeba infected cyst
      in the orbit.

PMID- 9541453
TI  - A computerised adaptometer.
AB  - PURPOSE: The design of an automatic instrument for the estimation of subjective
      dark adaptation (minimum perceptible for light) by an uninterrupted chain of
      trials. METHODS: A light emitting diode is used as test light. The patient
      answers by pressing a button when light is perceived. The process is controlled
      by means of a lap top computer and traces the adaptation course step by step.
      RESULTS: The instrument was tested by recording the course of dark adaptation
      (DA) in a clinical series of normals and of patients. The threshold sensitivity
      (after 25 min in darkness) showed very satisfying reproducibility. CONCLUSION:
      The instrument described was found to be reliable and well suited for clinical
      routine as well as experimental work.

PMID- 9541454
TI  - Antiphospholipid antibodies in patients with retinal vascular occlusions.

PMID- 9541455
TI  - The resistance of activated T-cells from SLE patients to apoptosis induced by
      human thymic stromal cells.
AB  - In this paper we show the differential sensitivity of phytohemagglutinine (PHA)
      activated T-cells from healthy donors or patients with systemic lupus
      erythematosus (SLE) to apoptosis induced by human thymic stromal cell line of
      epithelial origin. T-cells from SLE patients were mainly resistant to the
      apoptotic action of the stromal cells, while normal T-lymphocytes readily died
      via apoptosis. Gel electrophoresis revealed a DNA fragmentation pattern
      characteristic of apoptosis after 18 h of coculture. The simultaneous measurement
      of [3H]-thymidine uptake showed that the proliferative response of T-cells from
      SLE patients was significantly decreased compared to their normal counterparts.
      Such difference may account for the distinct result of interactions between the
      stromal and lymphoid cells, leading to the subsequent survival of T-lymphocytes
      from SLE patients. Nevertheless pretreatment of normal activated T-lymphocytes
      with anti-Fas mAbs, which have the capacity to substantially inhibit signaling
      through this receptor resulted in abolition of this form of programmed cell
      death. Thus, the precise role of Fas receptor and its ligand in this in vitro
      test system needs further investigation.

PMID- 9541456
TI  - Antibodies and T cells against synthetic peptides of the C-terminal domain (Hc)
      of botulinum neurotoxin type A and their cross-reaction with Hc.
AB  - Seventeen peptides containing T cell and/or antibody (Ab) epitopes previously
      localized on Hc of botulinum neurotoxin type A were used in SJL and BALB/c mice
      as immunogens either individually or as an equimolar mixture of groups that
      contained epitopes of T cells, Abs or both, to determine their abilities to
      generate T cells and/or Abs that recognize intact Hc. In SJL, peptide 897-915
      which included both T cell and Ab epitopes, elicited Abs that cross-reacted very
      strongly with Hc. In BALB/c, peptides 869-887, 883-901, 981-999 and 1275-1296
      which contained Ab epitopes generated Abs that cross-reacted strongly with Hc. A
      mixture of peptides that contained T cell and Ab epitopes was effective in both
      strains in eliciting T cells and Abs that cross-reacted with Hc. This mixture
      form gave a quicker rise (after two injections) in cross-reactive (with Hc) Ab
      titer as compared to other peptide mixtures or the individual peptides, and
      sustained in BALB/c a high Ab titer upon further booster injections. Some of the
      regions that elicited crossreactive immunity to Hc have sequence similarity to
      other clostridial toxins, suggesting that one or more of these synthetic peptides
      might provide cross-protection against those toxins.

PMID- 9541457
TI  - Induction of tetrahydrobiopterin synthesis in human umbilical vein smooth muscle
      cells by inflammatory stimuli.
AB  - Tetrahydrobiopterin (BH4) is an obligatory cofactor and regulator of nitric oxide
      synthases (NOS). We evaluated the biosynthesis of BH4 in human umbilical vein
      smooth muscle cells (HUVSMC). Trace amounts of BH4 were found intra- and
      extracellularly in untreated cells. When HUVSMC were activated by individual
      inflammatory stimuli (IL-1beta, TNFalpha, IFNgamma or LPS), both intra- and
      extracellular levels of BH4 increased significantly, with TNFalpha being the most
      potent single stimulus. Combined inflammatory cytokines synergized in the
      induction of an up to 600-fold increase of BH4 synthesis. Addition of LPS to the
      cytokine mixture led to a further increase of BH4 synthesis. Neopterin, a product
      of the first intermediate in BH4 biosynthesis, was also raised, but to a much
      lesser extent. The increase of BH4 synthesis was paralleled by an enhanced
      expression of isoform-1 (the only isoform coding for the active enzyme) of GTP
      cyclohydrolase I in cytokine treated cells. Our results show for the first time
      that BH4 biosynthesis is strongly induced by combinations of inflammatory stimuli
      in HUVSMC. The importance of BH4-dependent NO synthesis in HUVSMC needs, however,
      additional detailed studies.

PMID- 9541458
TI  - A new, striking morphological alteration of P-glycoprotein expression in NK cells
      from AIDS patients.
AB  - Natural killer cells from healthy donors express P-glycoprotein on their surface.
      This molecule is rearranged during the process of cell-mediated cytotoxicity and
      it appears to be clustered in the cell-to-cell contact regions. By contrast, in
      HIV-infected subjects this rearrangement is hindered. These results seem to be
      associated with cytoskeleton network alterations of the cell-mediated killing
      process occurring in AIDS patients and can contribute to the comprehension of the
      mechanisms of the natural killer cell deficiency found in these patients.

PMID- 9541459
TI  - Cellular expression of the cytolytic factor in earthworms Eisenia foetida.
AB  - Coelomic fluid of earthworms contains a 42 kDa protein designated CCF-1 (coelomic
      cytolytic factor 1), which accounts for approximately 40% of cytolytic activity
      of the entire coelomic fluid. CCF-1 was documented to be present on cells of the
      mesenchymal lining of the coelomic cavity as well as on free coelomocytes. Both
      cellular and humoral levels of CCF-1 were significantly increased after
      parenteral injection of endotoxin. Moreover, CCF-1 seems to be involved in cell
      mediated cytotoxicity, because cytotoxic activity is blocked in the presence of
      anti-CCF-1 monoclonal antibody (mAb).

PMID- 9541460
TI  - Modification of macrophage response to lipopolysaccharide by fetuin.
AB  - The physiological role(s) of fetuin, a protein present in plasma and many tissues
      of developing animals at levels much higher than in the adult, is unknown. Here
      we show that fetuin can modify the responses of macrophages to lipopolysaccharide
      (LPS) stimulation. At concentrations of fetuin in the medium, corresponding to
      fetal levels of this protein in plasma, the production and secretion of
      interleukin 1beta (IL-1beta) and nitric oxide (NO) is almost abolished, tumour
      necrosis factor-alpha (TNF-alpha) reduced, while that of IL-6 is not affected. On
      the other hand, concentrations of fetuin corresponding to adult plasma levels
      (i.e. 40-60 mg/100 ml) were without much effect on macrophage synthesis and
      secretion of these cytokines.

PMID- 9541461
TI  - Induction of pulmonary immunity in cattle by oral administration of ovalbumin in
      alginate microspheres.
AB  - Respiratory infectious diseases are an important cause of economic losses to the
      cattle industry. There is a need for an effective, easy to administer vaccine to
      the critical bacterial pathogens that cause pneumonia in cattle. An orally
      administered vaccine could be given to a large number of animals without
      significant stress to the animals and with minimal labor. The purpose of this
      study was to determine whether the oral administration of a model antigen
      (ovalbumin) in alginate microspheres could induce pulmonary immunity in cattle.
      Calves were vaccinated orally with ovalbumin (OVA) following either a
      subcutaneous (s.c.) or oral priming dose of OVA. Calves primed and boostered by
      oral administration (oral/oral) of OVA encapsulated in alginate microparticles
      had increased numbers of antigen-specific IgA ASCs (ASCs) in bronchoalveolar
      lavage (BAL) fluids. Calves that received a s.c. priming followed by an oral
      booster inoculation (s.c./oral) of OVA in alginate microspheres had a greater
      number of anti-OVA IgA, IgG1 and IgG2 ASCs in BALF. S.c./oral calves also had
      increased numbers of anti-OVA IgG1 ASCs in peripheral blood whereas oral/oral
      calves had none. S.c./oral calves had increased anti-OVA IgG1, IgG2, and IgA
      titers in BALF, and IgG1 and IgG2 in serum compared to both oral/oral and sham
      vaccinated calves. These results indicate that oral administration of antigen
      encapsulated in alginate microspheres results in a mucosal immune response in the
      respiratory tract of cattle. Furthermore, s.c. priming both enhanced the IgA
      response and stimulated an IgG1 and IgG2 response not seen in oral/oral calves.
      The difference in antibody isotype results suggest that design of the vaccination
      protocol can direct antibody responses as needed for a specific immunization
      program.

PMID- 9541462
TI  - Cytokine production in PBMC from allergics and non-allergics following in vitro
      allergen stimulation.
AB  - Dysregulation of cytokine production in atopic individuals has previously been
      clearly demonstrated. In the present study we aimed to assess whether a prolonged
      in vitro exposure of peripheral blood lymphocytes (PBMC) to allergen would result
      in a, by time, changed cytokine profile in allergic subjects. Blood was taken
      from 11 atopic asthmatic subjects and nine healthy non-atopic controls during the
      birch pollen season. PBMC were stimulated with birch pollen allergen (100, 1000
      and 10,000 SQ-U/ml). After different times of exposure (1, 3 and 5 weeks)
      interleukin (IL)-5 and interferon-gamma (IFN-gamma) production was measured.
      Prior to the IL5 and IFN-gamma determinations, PHA was added to the cultures to
      ensure maximal release of cytokines. The asthmatic group always displayed a lower
      IFN-gamma:IL-5 ratio. Significant differences in ratio between the two groups
      were observed. Furthermore, PBMC challenged in vitro with 10,000 SQ-U/ml resulted
      in significantly elevated levels of IL-5 in the asthmatic group compared to the
      control group when determined after 3 and 5 weeks stimulation. In the asthmatic
      group the balance between IL-5 and IFN-gamma is shifted towards increased IL-5
      production following prolonged in vitro stimulation. This might illustrate the in
      vivo situation, where an increased IL-5 production is of importance in the
      pathogenesis of asthma.

PMID- 9541463
TI  - Flow cytometric detection of perforin in normal human lymphocyte subpopulations
      defined by expression of activation/differentiation antigens.
AB  - We investigated with three-color flow cytometry the expression of perforin (Pf)
      in normal human lymphocyte subpopulations identified by means of activation and
      differentiation-related antigens. Interestingly, Pf could be detected in a
      substantial subset (13 +/- 2%) of memory CD4+ CD45RO+ cells, on relevant
      percentages of memory (CD45RO+) and naive (CD45RA+) CD8+ cells and on virtually
      all CD3- CD16+, CD3- CD56+ and NKB1+ natural killer cells, as expected. The
      analysis of fluorescence intensity showed higher levels of Pf expression on
      CD8dim and NK cells compared to CD8bright and CD4+ lymphocytes, Pf and CD69, HLA
      DR, CD95 and CD25 activation/differentiation-related antigens were never co
      expressed. On average, 15 +/- 3% of CD3+ CD28+ cells were found to be Pf+, in
      line with a previously activated or memory cell type. Comparable percentages of
      CD8+ CD11b- (cytotoxic) and CD8+ CD11b+ (suppressor) T cells were Pf+.
      Multiparameter flow cytometry is a powerful tool to detect minute fractions of Pf
      expressing cells in heterogeneous populations.

PMID- 9541464
TI  - The vasoactive intestinal peptide analogue RO25-1553 inhibits the production of
      TNF and IL-12 by LPS-activated monocytes.

PMID- 9541465
TI  - Ulex europaeus agglutinin-I binds to developing gastrin cells.
AB  - We have previously reported that antropyloric gastrin (G) and somatostatin (D)
      cells derive from precursor (G/D) cells that coexpress both hormones. We have now
      analyzed this endocrine cell pedigree for binding of Ulex europaeus agglutinin-I
      (UEA-I), which previously has been reported to represent a useful marker for cell
      differentiation. Subpopulations of G/D, D, and G cells were all found to express
      UEA-I binding. Labelling with bromodeoxyuridine showed that UEA-I positive G
      cells possessed a higher labelling index than UEA-I negative G cells. These data
      suggest that the UEA-I positive G cells represent maturing cells still involved
      in DNA synthesis and cell division. Electron microscopically, specific UEA-I
      binding sites were localized to the secretory granules and the apical cell
      membrane of G cells. We conclude that UEA-I represents a differentiation marker
      for G cells. Moreover, the presence of UEA-I binding sites in these cells may be
      relevant for Helicobacter pylori-mediated disturbances of gastric acid secretion
      and gastrin hypersecretion.

PMID- 9541466
TI  - Sulfated glycosaminoglycans in guinea pig basophils studied by means of cationic
      colloidal gold.
AB  - Bone marrow embedding in the hydrophilic resin, Lowicryl K4M, followed by
      cationic colloidal gold (CCG, pH 1.0) staining was used to study the sulfated
      glycosaminoglycans (GAGs) and their sites of sulfation ultrastructurally in
      various maturational stages of both basophil granulocytes and basophil granules
      in the guinea pig. CCG at pH 1.0 is specific for sulfated GAG staining. Basophil
      granulocytes and granules reacted positively to CCG with a variety of staining
      according to the stage of maturation. The formation of basophil granules takes
      place throughout the myelocyte stage. Early basophil myelocytes contain a large
      Golgi apparatus with active granulogenesis, while late myelocytes contain a small
      and less active Golgi apparatus as judged by CCG staining. All the immature
      granules and some of the granules with characteristic ultrastructure stained
      positively. However, some of the mature granules had lost their affinity for CCG
      upon maturation. Interestingly, strongly positive CCG staining was also observed
      in the trans to transmost Golgi apparatus. This indicates that sulfation of GAGs
      occurs in the trans to transmost Golgi apparatus in all maturational stages of
      basophil granulocytes. Treatment with chondroitinase ABC or heparinase I
      abolished the majority of CCG staining.

PMID- 9541467
TI  - c-kit immunoreactive interstitial cells of Cajal in the human small and large
      intestine.
AB  - c-kit immunohistochemistry was performed on unfixed frozen sections of human
      small (duodenum, jejunum, and ileum) and large intestine (ascending, transverse,
      descending, and sigmoid colon). The c-kit immunoreactive cells in the muscularis
      externa of the intestinal wall were identified as interstitial cells of Cajal
      (ICC) and mast cells. ICC were identified by their morphology, localization, and
      organization based on previous light and electron microscopic studies. In the
      small intestine, ICC were located primarily in relation to the myenteric plexus
      of Auerbach, but also in septa between circular muscle lamellae. In the large
      intestine, ICC were seen in relation to Auerbach's plexus, but also and in great
      numbers in the circular muscle layer and in teniae of the longitudinal muscle
      layer. The morphology of the ICC was similar in the small and large intestine,
      but the pattern of distribution was obviously different. c-kit immunoreactive
      mast cells were found predominantly in the inner part of the circular muscle
      layer. The anti-c-kit method is found to be an easy and reliable method to study
      at least most of the interstitial cells of Cajal and thereby contribute to
      further normal and pathological studies.

PMID- 9541468
TI  - Localization of cAMP-dependent signal transducers in early rat liver
      carcinogenesis.
AB  - Cyclic AMP (cAMP) is an important regulator of liver growth and differentiation.
      The main intracellular cAMP receptor, cAMP-dependent protein kinase (PKA),
      consists of two regulatory (R) and two catalytic (C) subunits. There are two
      classes, RI and RII, of the regulatory subunit, giving rise to type I (RI2C2) and
      type II (RII2C2) PKA. The RI/RII ratio generally decreases during organ
      development, and increases during carcinogenesis. Alterations in this ratio have
      been implicated as an important factor in experimental and clinical
      carcinogenesis. We have studied the expression of RIalpha, RIIalpha, Calpha, and
      an important substrate of PKA, the cAMP-response element binding protein, during
      rat liver carcinogenesis. Two-color immunofluorescence and confocal laser scan
      microscopy were used to characterize localization of the cAMP-dependent signal
      transducers in hepatocytes, bile ducts, oval cells, and preneoplastic lesions. We
      found that bile ducts and oval cells (putative liver stem cells) contained a
      higher RI/RII ratio than hepatocytes and preneoplastic lesions. Thus, an altered
      RI/RII ratio was not detected during early rat liver carcinogenesis, but may
      contribute to differentiation of putative liver stem cells to hepatocytes.

PMID- 9541469
TI  - Localization and development of chromogranin A and luteinizing hormone
      immunoreactivities in the secretory-specific cells of the hypophyseal pars
      tuberalis of the chicken.
AB  - The pars tuberalis mainly consists of the secretory cells specific to this
      portion of the pituitary. We examined the localization and development of
      luteinizing hormone (LH) and chromogranin A in the chicken pars tuberalis by
      immunohistochemistry. The vast majority of the chicken pars tuberalis was
      occupied by cells immunoreactive for both LH and chromogranin A. Furthermore,
      immunoblot analysis of chicken pars tuberalis extracts with LH antiserum
      demonstrated that two bands, the large alpha-subunit and small beta-subunit of
      the LH molecule, were expressed in this tissue as well as in the pars distalis. A
      band for chromogranin A was also detected in pars tuberalis extracts with
      chromogranin A antiserum. In contrast to the cells of mammalian species that
      contain only a few small secretory granules, the specific cells of the chicken
      pars tuberalis were characterized by the presence of many secretory granules
      ranging from 90 to 400 nm in diameter. Postembedding immunogold labeling showed
      that gold particles representing immunoreactivity for LH were densely located on
      all secretory granules of the secretory-specific cells. Many secretory granules,
      especially the large ones, of the cells were also loaded with immunogold
      particles for chromogranin A. Double immunogold labeling confirmed that LH and
      chromogranin A were colocalized on the same secretory granules. During embryonic
      development, the primordium of the pars tuberalis was first detected at 8 days of
      incubation as a small group of cells containing LH- and chromogranin
      immunoreactive cells. In the pars distalis, the onset of LH and chromogranin
      expression occurred earlier, at 6 days of incubation. At 10 days of incubation,
      the pars tuberalis primordium became large cell masses consisting of LH- and
      chromogranin-immunoreactive cells, which were located close to the median
      eminence. Subsequently, the primordium extended along the median eminence
      progressively with age. At 14 days of incubation, it reached to the rostral end
      and surrounded the median eminence as slender cell cords. These results indicate
      that specific cells of the chicken pars tuberalis synthesize a glycoprotein
      hormone related to the LH molecule, which is stored in the secretory granules
      together with chromogranin A. The pars tuberalis may be involved in the
      regulation of gonadal function in a different way from that of the pars distalis.

PMID- 9541470
TI  - Immunocytochemical study of lysosomal proteins with a new monoclonal antibody
      directed against epithelioid macrophages.
AB  - A monoclonal antibody, EPI-1, was produced against macrophages in epithelioid
      granulomas induced in rat foot pads by muramyl dipeptide. This EPI-1 antibody
      reacted to lysosome-like structures in epithelioid macrophages, peritoneal and
      pulmonary macrophages, and also in other tissues such as liver, testes, and
      kidneys. Western blot analysis of epithelioid granulomas, liver, testes, and
      kidneys revealed the same positive band of 62 kDa. Immunoelectron microscopic
      study of foot pad granulomas and hepatocytes demonstrated the EPI-1 antigen
      located in lysosomes and autophagic vesicles, preferentially along their
      membranes. These findings suggest that the EPI-1 antibody may recognize a novel
      antigen related to lysosomal membrane proteins in macrophages and other cells,
      which is useful for identifying lysosomes and their related structures.

PMID- 9541471
TI  - Expression of class III beta-tubulin in normal and neoplastic human tissues.
AB  - The class III beta-tubulin isotype is widely used as a neuronal marker in normal
      and neoplastic tissues. This isotype was, however, also immunodetected in certain
      tumours of non-neuronal origin such as squamous cell carcinoma. Using a newly
      described monoclonal antibody we compared the distribution of class III beta
      tubulin in normal and neoplastic tissues. The TU-20 mouse monoclonal antibody was
      prepared against a conserved synthetic peptide from the C-terminus of the human
      class III beta-tubulin isotype, and its specificity was confirmed by
      immunoblotting, by competitive enzyme-linked immunosorbent assay and by
      immunofluorescence microscopy on cultured cells. In different cell lines of
      various origins the antibody reacted only with neuroblastoma Neuro-2a cells and
      with embryonal carcinoma P19 cells stimulated to neuronal differentiation by
      retinoic acid. Immunohistochemistry on formaldehyde-fixed paraffin-embedded
      normal human tissues revealed the presence of the class III beta-tubulin isotype
      in cell bodies and processes of neuronal cells in the peripheral and central
      nervous systems. In other tissues, this beta-tubulin isotype was not
      immunodetected. Class III beta-tubulin was found in all cases of
      ganglioneuroblastoma, ganglioneuroma, medulloblastoma, neuroblastoma,
      sympathoblastoma and in one case of teratoma. In contrast, no reactivity was
      detected in tumours of non-neuronal origin, including 32 cases of squamous cell
      carcinoma. The results indicate a specific TU-20 epitope expression exclusively
      in neuronal tissues. The antibody could thus be a useful tool for the probing of
      class III beta-tubulin functions in neurons as well as for immunohistochemical
      characterisation of tumours of neuronal origin.

PMID- 9541472
TI  - Cytochemical localisation of the NADPH diaphorase activity in the Leydig cells of
      the mouse.
AB  - The distribution of the NADPH diaphorase activity was studied in mouse Leydig
      cells by means of light and electron microscopy. When observed by the light
      microscope, most Leydig cells appeared intensely stained; a few cells (about 10%)
      showed a slightly positive or apparently negative reaction. The inhibitory
      effects of N(G)-nitro-L-arginine and iodonium diphenyl on frozen sections suggest
      the colocalisation of NADPH diaphorase reaction with nitric oxide synthase. The
      ultrastructural study revealed that all the Leydig cells were positively stained
      for NADPH diaphorase; however, a small number of cells displayed weak enzymatic
      activity. The reaction product was located in the mitochondria, smooth
      endoplasmic reticulum and lipidic vacuoles, and the nuclear envelope was also
      stained. The possible meaning of the NADPH diaphorase activity in the Leydig
      cells of mice was discussed.

PMID- 9541473
TI  - Evidence of ED-B+ fibronectin synthesis in human tissues by non-radioactive RNA
      in situ hybridization. Investigations on carcinoma (oral squamous cell and breast
      carcinoma), chronic inflammation (rheumatoid synovitis) and fibromatosis (Morbus
      Dupuytren).
AB  - The splicing variant of fibronectin containing the ED-B domain (oncofoetal
      fibronectin) occurs in foetal tissues, reparative processes, organ fibrosis and
      in tumour tissues. Consequently, a supportive effect of ED-B+ fibronectin for
      tissue remodelling and tumour progression is assumed. A non-radioactive RNA-RNA
      in situ hybridization protocol for the investigation of ED-B+ fibronectin
      synthesis applicable in human tissues is introduced. The ED-B+ fibronectin
      synthesis was investigated in human disease processes, for which the occurrence
      of ED-B+ fibronectin is well demonstrated by immunohistochemistry (rheumatoid
      arthritis, oral squamous cell carcinoma, invasive ductal carcinoma of the breast
      and nodular palmar fibromatosis). The ED-B+ fibronectin synthesis could be shown
      in lining cells and in endothelial cells of synovial villi in rheumatoid
      arthritis, in stromal cells of oral squamous cell carcinoma and invasive ductal
      carcinoma and in fibro-/myofibroblasts in the proliferative and early
      involutional phase of nodular palmar fibromatosis. By means of double labelling
      (alpha-smooth muscle actin immunostaining - ED-B+ fibronectin in situ
      hybridization), the ED-B+ fibronectin synthesis could be shown to be a typical
      feature of myofibroblasts. In contrast to the often diffuse ED-B+ fibronectin
      immunostaining, only a few synthetically active stromal cells were observed
      focally accentuated within the tumour, which were interpreted as hot spots of
      tumour-stroma interaction.

PMID- 9541474
TI  - Thyroid C cells of middle-aged rats treated with estradiol or calcium.
AB  - The structure and function of C cells of middle-aged female rats (14-months old)
      treated with estradiol dipropionate (EDP), calcium (Ca) or a combination of
      EDP+Ca were studied. A stereological method was used to determine the volume of
      calcitonin (CT)-immunoreactive C cells and their nuclei, and the relative volume
      density and mean number of the C cells per section were calculated. Serum levels
      of CT, osteocalcin, parathyroid hormone (PTH), and beta-estradiol were also
      measured. A significant decrease in body weight of the rats treated with EDP or
      EDP+Ca was observed. These treatments led to a significant decrease in cellular
      and nuclear volumes, relative volume density, and mean number of C cells per
      section, in comparison with the corresponding controls. A reduction of the serum
      level of CT, PTH, and osteocalcin was also recorded in EDP- and EDP+Ca-treated
      animals. No statistically significant differences between Ca- and vehicle
      injected rats, with regard to all morphometric C cell parameters and biochemical
      values determined, were seen. However, a conspicuous degranulation of the C cells
      and decreased immunoreactivity for CT in the Ca-receiving group, which could be
      interpreted as the signs of increased activity of these cells, were noticed. This
      effect of Ca was also observed in rats injected with EDP and Ca in combination,
      when the inhibitory effect of EDP on C cell function was less noticeable than in
      the group treated with EDP alone.

PMID- 9541475
TI  - Uroplakins and cytokeratins in the regenerating rat urothelium after sodium
      saccharin treatment.
AB  - A sodium saccharin (NaSac) diet was used to induce cell damage and regeneration
      in the urothelium of the male rat urinary bladder. Foci of terminally
      differentiated superficial cell exfoliation were detected after 5 weeks and their
      number increased after 10 and 15 weeks of the diet. At the sites of superficial
      cell loss, regenerative simple hyperplasia developed. Within 5 weeks of NaSac
      removal, regeneration re-established normal differentiated urothelium. In order
      to follow urothelial differentiation during regeneration we studied the
      expression of uroplakins and cytokeratins by means of immunocytochemistry and
      immunohistochemistry, respectively. Normal urothelium was characterised by
      terminally differentiated superficial cells which expressed uroplakins in their
      luminal plasma membrane and cytokeratin 20 (CK20) in the cytoplasm. Basal and
      intermediate cells were CK20 negative and cytokeratin 17 (CK17) positive. In
      hyperplastic urothelium all cells synthesised CK17, but not CK20. Differentiation
      of the superficial layer was reflected in three successive cell types: cells with
      microvilli, cells with rounded microridges and those with a rigid-looking plasma
      membrane on the luminal surface. The cells with microvilli did not stain with
      anti-uroplakin antibody. When the synthesis of uroplakins was detected rounded
      microridges were formed. With the elevated expression of uroplakins the luminal
      plasma membrane becomes rigid-looking which is characteristic of asymmetric unit
      membrane of terminally differentiated cells. During differentiation, synthesis of
      CK17 ceased in superficial cells while the synthesis of CK20 started. These
      results indicate that during urothelial regeneration after NaSac treatment,
      specific superficial cell types develop in which the switch to uroplakin
      synthesis and transition from CK17 to CK20 synthesis are crucial events for
      terminal differentiation.

PMID- 9541476
TI  - Mapping of D1 dopamine receptor mRNA by non-radioactive in situ hybridization.
AB  - In order to improve the identification and characterization of dopaminoceptive
      neurons, the rat brain was mapped for D1 dopamine receptor mRNA by non
      radioactive in situ hybridization (ISH) with a 45mer digoxigenin-labeled
      oligonucleotide probe. The specificity of the results was controlled with the
      help of a 396-bp D1 receptor riboprobe. Labeled hybrids were visualized with an
      alkaline phosphatase-coupled anti-digoxigenin antibody. The high resolution
      obtained permitted individual labeled cells to be identified and to distinction
      between cell bodies and processes. D1 mRNA was largely confined to neurons. With
      the exception of ependymal cells, glial cells were not distinctly labeled.
      Subcellularly, D1 mRNA was localized to perikarya but not to dendrites or axons.
      D1 receptor-expressing neurons were present in all of the known terminal fields
      of mesencephalic or diencephalic dopaminergic neurons. However, D1 message was
      also detected in brain areas which are not known to contain D1 ligand binding
      sites or in which the presence or the cellular source of this receptor subtype
      had previously not been unequivocally established, such as the hippocampus or
      cerebellar cortex. Moreover, labeled neurons were present in regions not known to
      receive dopaminergic projections, such as the thalamic and some brainstem nuclei.
      We conclude that this ISH technique provides a considerable gain in sensitivity
      and resolution with regard to neurotransmitter receptor mapping.

PMID- 9541477
TI  - Innervation of developing human taste buds. An immunohistochemical study.
AB  - Morphological changes in developing human gustatory papillae during the 6th to
      the 23rd postovulatory week have been studied. The general innervation pattern of
      taste papillae and taste bud primordia was revealed immunohistochemically using
      antibodies against protein gene product 9.5 (PGP9.5), neurofilament H (NFH),
      neurofilament L (NFL), neurone-specific enolase (NSE), and tubulin. The autonomic
      and somatosensory nerve supply has been investigated using antibodies against
      substance P (SP), calcitonin gene-related peptide (CGRP), tyrosine hydroxylase
      (TH), neuropeptide Y (NPY), the neuronal form of nitric oxide synthase (n-NOS),
      and, enzyme histochemically, NADPH-diaphorase. Nerve fibers approach the basal
      membrane of the lingual epithelium around the 7th postovulatory week and invade
      the epithelium of papilla-like structures at the 8th week, but some also
      penetrate the basal membrane of the non-papillary epithelium. They are in close
      contact with slender epithelial cells that are considered to be the taste bud's
      progenitor cells. Early human taste buds situated at the anterior part of the
      tongue do not necessarily require a dermal (later fungiform) papilla. The NADPH
      diaphorase reaction revealed positive results in dermal nerve fibers, but the
      immunohistochemical reaction against n-NOS was negative. Immunohistochemical
      detection of neuropeptides and vasoactive substances rendered negative results
      for developmental stages of 7-18 postovulatory weeks. By the 18th week, only SP
      was detected in dermal papillae, but not in the vicinity of taste buds'
      primordia. Thus, autonomic and somatosensory nerves seem not to play a key role
      in formation and maintenance of early human taste buds.

PMID- 9541479
TI  - Type 1 Gaucher disease: phenotypic expression and natural history in Japanese
      patients.
AB  - Gaucher disease is caused by a deficiency of glucocerebrosidase, resulting in
      hepatosplenomegaly, pancytopenia, growth retardation and skeletal involvement. We
      analyzed data on genotype and key clinical parameters in 35 Japanese patients
      with Gaucher disease type 1. Our data demonstrated that over 60% of patients had
      onset of Gaucher disease signs/symptoms at less than 5 years. Sixty percent and
      46% of evaluable patients were splenectomized and developed severe bone
      involvement, respectively. Within mean follow-up periods of 8 years and 4 months,
      mean relative height and weight, severity score index and platelet count all
      worsened to a highly significant degree. These data suggest that type 1 Gaucher
      disease tends to be severe and progressive in Japanese patients, most of whom
      would be suitable for treatment and might indeed require earlier and more
      aggressive therapy.

PMID- 9541480
TI  - Commentary: the natural history of Gaucher disease.

PMID- 9541481
TI  - "A rare disorder, yes; an unimportant one, never".

PMID- 9541482
TI  - Neurokinin-1 (NK-1) receptor is required in Clostridium difficile- induced
      enteritis.
AB  - Toxin A, a 308,000-Mr enterotoxin from Clostridium difficile, mediates antibiotic
      associated diarrhea and colitis in humans. Injection of toxin A into animal
      intestine triggers an acute inflammatory response characterized by activation of
      sensory neurons and immune cells of the intestinal lamina propria, including mast
      cells and macrophages, and migration of circulating neutrophils in the involved
      intestinal segment. In this study we show that mice genetically deficient in the
      neurokinin-1 receptor are protected from the secretory and inflammatory changes
      as well as from epithelial cell damage induced by toxin A. The protective effect
      of neurokinin-1R deletion correlates with diminished intestinal levels of the
      cytokine TNF-alpha and its mRNA and the leukocyte enzyme myeloperoxidase. These
      results demonstrate a major requirement for substance P receptors in the
      pathogenesis of acute inflammatory diarrhea.

PMID- 9541483
TI  - Enhanced coronary vasa vasorum neovascularization in experimental
      hypercholesterolemia.
AB  - Coronary arteries contain a network of vasa vasorum in the adventitia. The three
      dimensional anatomy of the vasa vasorum in early coronary atherosclerosis is
      unknown. This study was designed to visualize and quantitate the three
      dimensional spatial pattern of vasa vasorum in normal and experimental
      hypercholesterolemic porcine coronary arteries, using a novel computed tomography
      technique. Animals were killed after being fed either a high cholesterol diet (n
      = 4) or a control diet (n = 4) for 12 wk. The proximal left anterior descending
      coronary artery was removed from the heart, scanned, and reconstructed, and
      quantitation of vasa vasorum density was performed. Two different types of vasa
      vasorum were defined: first-order vasa vasorum ran longitudinally parallel to the
      vessel and second-order originated from first-order vasa circumferentially around
      the vessel wall. Compared with controls in hypercholesterolemic coronary
      arteries, there was a significant increase in the area of the vessel wall (3.86+/
      0.22 vs. 8.07+/-0.45 mm2, respectively, P < 0.01) and in the density of vasa
      vasorum (1. 84+/-0.05/mm2 vs. 4.73+/-0.24/mm2; respectively, P = 0.0001). This
      occurred especially by an increase of second-order vasa vasorum and
      disorientation of normal vasa vasorum spatial pattern. This study suggests that
      adventitial neovascularization of vasa vasorum occurs in experimental
      hypercholesterolemic coronary arteries and may be a part of the early
      atherosclerotic remodeling process.

PMID- 9541484
TI  - Adipocyte macrophage colony-stimulating factor is a mediator of adipose tissue
      growth.
AB  - Adipose tissue growth results from de novo adipocyte recruitment (hyperplasia)
      and increased size of preexisting adipocytes. Adipocyte hyperplasia accounts for
      the severalfold increase in adipose tissue mass that occurs throughout life, yet
      the mechanism of adipocyte hyperplasia is unknown. We studied the potential of
      macrophage colony-stimulating factor (MCSF) to mediate adipocyte hyperplasia
      because of the profound effects MCSF exerts on pluripotent cell recruitment and
      differentiation in other tissues. We found that MCSF mRNA and protein were
      expressed by human adipocytes and that adipocyte MCSF expression was upregulated
      in rapidly growing adipose tissue that encircled acutely inflamed bowel and in
      adipose tissue from humans gaining weight (4-7 kg) with overfeeding. Localized
      overexpression of adipocyte MCSF was then induced in rabbit subcutaneous adipose
      tissue in vivo using adenoviral-mediated gene transfer. Successful overexpression
      of MCSF was associated with 16-fold increases in adipose tissue growth compared
      with a control adenovirus expressing beta-galactosidase. This occurred in the
      absence of increased cell size and in the presence of increased nuclear staining
      for MIB-1, a marker of proliferation. We conclude that MCSF participates in
      adipocyte hyperplasia and the physiological regulation of adipose tissue growth.

PMID- 9541485
TI  - Gene transfer to the rodent placenta in situ. A new strategy for delivering gene
      products to the fetus.
AB  - The delivery of biologically active factors to the developing mammalian embryo by
      in utero gene transfer has generated considerable interest but limited success.
      The chorioallantoic placenta is a potential alternative target for providing
      therapeutic transgenes to the fetus during gestation. We demonstrate that somatic
      gene transfer to the midgestation rat placenta may be efficiently accomplished in
      situ through the implantation of a variety of genetically modified cells with
      different antigenic and growth properties. Ex vivo-modified cells survived and
      retained transgene expression until term. Proteins secreted from the transplanted
      cells were detectable within the fetal trunk blood. These studies suggest that
      gene transfer to the placenta may be a useful tool for answering questions of
      both embryonic and placental development and providing therapeutic proteins
      during gestation for amelioration of diseases with onset during embryonic life.

PMID- 9541486
TI  - Tumorigenic conversion of p53-deficient colon epithelial cells by an activated Ki
      ras gene.
AB  - Distinct genetic abnormalities (loss-of-function mutations of APC and p53 and
      oncogenic activation of Ki-ras) are associated with specific stages of the
      sporadic, most common types of colorectal tumors. However, the inability to
      maintain primary colon epithelial cells in culture has hindered the analysis of
      the pathogenetic role of these abnormalities in colorectal tumorigenesis. We have
      now established primary cultures of epithelial cells from the colon crypts of p53
      deficient mice; these cells are nontumorigenic as indicated by their failure to
      form colonies in soft agar and to grow as tumors in immunodeficient SCID mice and
      in immunocompetent syngeneic hosts. Upon ectopic expression of an activated Ki
      ras gene, p53-deficient colon epithelial cells form colonies in soft agar and
      highly invasive subcutaneous tumors in both immunodeficient and immunocompetent
      mice. Ectopic expression of wild-type p53, but not of a DNA-binding-deficient
      mutant, markedly suppressed the colony-forming ability of the Ki-ras-transformed
      p53-deficient epithelial cells. Together, these findings establish a functional
      synergism in colorectal tumorigenesis dependent on the effects of an oncogenic Ki
      ras in a p53-deficient background. This model of tumorigenic conversion of colon
      epithelial cells might be useful to identify genetic changes associated with
      disease progression and to evaluate the therapeutic response to conventional and
      novel anticancer drugs.

PMID- 9541487
TI  - Paraoxonase inhibits high-density lipoprotein oxidation and preserves its
      functions. A possible peroxidative role for paraoxonase.
AB  - HDL levels are inversely related to the risk of developing atherosclerosis. In
      serum, paraoxonase (PON) is associated with HDL, and was shown to inhibit LDL
      oxidation. Whether PON also protects HDL from oxidation is unknown, and was
      determined in the present study. In humans, we found serum HDL PON activity and
      HDL susceptibility to oxidation to be inversely correlated (r2 = 0.77, n = 15).
      Supplementing human HDL with purified PON inhibited copper-induced HDL oxidation
      in a concentration-dependent manner. Adding PON to HDL prolonged the oxidation
      lag phase and reduced HDL peroxide and aldehyde formation by up to 95%. This
      inhibitory effect was most pronounced when PON was added before oxidation
      initiation. When purified PON was added to whole serum, essentially all of it
      became HDL-associated. The PON-enriched HDL was more resistant to copper ion
      induced oxidation than was control HDL. Compared with control HDL, HDL from PON
      treated serum showed a 66% prolongation in the lag phase of its oxidation, and up
      to a 40% reduction in peroxide and aldehyde content. In contrast, in the presence
      of various PON inhibitors, HDL oxidation induced by either copper ions or by a
      free radical generating system was markedly enhanced. As PON inhibited HDL
      oxidation, two major functions of HDL were assessed: macrophage cholesterol
      efflux, and LDL protection from oxidation. Compared with oxidized untreated HDL,
      oxidized PON-treated HDL caused a 45% increase in cellular cholesterol efflux
      from J-774 A.1 macrophages. Both HDL-associated PON and purified PON were potent
      inhibitors of LDL oxidation. Searching for a possible mechanism for PON-induced
      inhibition of HDL oxidation revealed PON (2 paraoxonase U/ml)-mediated hydrolysis
      of lipid peroxides (by 19%) and of cholesteryl linoleate hydroperoxides (by 90%)
      in oxidized HDL. HDL-associated PON, as well as purified PON, were also able to
      substantially hydrolyze (up to 25%) hydrogen peroxide (H2O2), a major reactive
      oxygen species produced under oxidative stress during atherogenesis. Finally, we
      analyzed serum PON activity in the atherosclerotic apolipoprotein E-deficient
      mice during aging and development of atherosclerotic lesions. With age, serum
      lipid peroxidation and lesion size increased, whereas serum PON activity
      decreased. We thus conclude that HDL-associated PON possesses peroxidase-like
      activity that can contribute to the protective effect of PON against lipoprotein
      oxidation. The presence of PON in HDL may thus be a major contributor to the
      antiatherogenicity of this lipoprotein.

PMID- 9541488
TI  - Construction of a double congenic strain to prove an epistatic interaction on
      blood pressure between rat chromosomes 2 and 10.
AB  - Previously we presented suggestive evidence from an F2 segregating population for
      an interaction on blood pressure (BP) between quantitative trait loci (QTL) on
      rat chromosomes (Chr) 2 and 10. To prove the existence of such an interaction, we
      developed congenic strains for Chr 2 and 10 by introgressing the low BP QTL
      alleles into the Dahl salt-sensitive (S) strain. A double congenic strain was
      also constructed with both the Chr 2 and 10 low BP QTL alleles on the S
      background. The four strains (S, Chr 2 congenic, Chr 10 congenic, and Chr 2/10
      double congenic) were studied for BP response to increased salt intake. An
      analysis of variance showed significant main effects of Chr 2, Chr 10, and a
      significant interaction between Chr 2 and 10 on BP and heart weight (all P <
      0.0001). The interaction accounted for 24 mmHg of BP and 79 mg of heart weight.
      Thus, the discovery and proof of epistatic interactions are clearly critical to
      understanding the genetics of blood pressure.

PMID- 9541489
TI  - Abnormal cancellous bone collagen metabolism in osteoarthritis.
AB  - Biochemical investigations into the pathogenesis of osteoarthritis have, for the
      last two decades, concentrated on the mechanisms involved in the destruction of
      the articular cartilage. Although bone changes are known to occur, the
      biochemistry of the collagenous matrix within osteoarthritic bone has received
      scant attention. We report that bone collagen metabolism is increased within
      osteoarthritic femoral heads, with the greatest changes occurring within the
      subchondral zone. Collagen synthesis and its potential to mineralize were
      determined by the carboxy-terminal propeptide content and alkaline phosphatase
      activity, respectively. These data supported elevated new matrix formation. Our
      finding of a three- to fourfold increase in TGF-beta in osteoarthritic bone
      indicates that this might represent a stimulus for the increased collagen
      synthesis observed. Of additional significance is the hypomineralization of
      deposited collagen in the subchondral zone of osteoarthritic femoral heads,
      supporting a greater proportion of osteoid in the diseased tissue. The cross
      linking of collagen was similar to that observed for controls. In addition, the
      degradative potential of osteoarthritic bone was considerably higher as
      demonstrated by increased matrix metalloproteinase 2 activity, and again the
      greater activity was associated with the subchondral bone tissue. The
      polarization exhibited in the metabolism of bone collagen from osteoarthritic
      hips might exacerbate the processes involved in joint deterioration by altering
      joint morphology. This in turn may alter the distribution of mechanical forces to
      the various tissues, to which bone is a sensitive responder. Bone collagen
      metabolism is clearly an important factor in the pathogenesis of osteoarthritis
      and certainly warrants further biochemical study.

PMID- 9541491
TI  - Epicutaneous sensitization with protein antigen induces localized allergic
      dermatitis and hyperresponsiveness to methacholine after single exposure to
      aerosolized antigen in mice.
AB  - Our understanding of the pathogenesis of atopic dermatitis (AD) and its
      relationship to asthma remains incomplete. Herein, we describe a murine model of
      epicutaneous (EC) sensitization to the protein allergen, chicken egg albumin,
      ovalbumin (OVA), which results in a rise in total and OVA-specific serum IgE and
      leads to the development of a dermatitis characterized by infiltration of CD3(+)
      T cells, eosinophils, and neutrophils and by local expression of mRNA for the
      cytokines IL-4, IL-5, and interferon-gamma. A single exposure of the EC
      sensitized mice to aerosolized OVA induced eosinophilia in the bronchoalveolar
      lavage fluid and airway hyperresponsiveness to intravenous methacholine as
      assessed by measurement of pulmonary dynamic compliance (Cdyn). These results
      suggest a possible role for EC exposure to antigen in atopic dermatitis and in
      the development of allergic asthma.

PMID- 9541490
TI  - Helicobacter pylori upregulates expression of epidermal growth factor-related
      peptides, but inhibits their proliferative effect in MKN 28 gastric mucosal
      cells.
AB  - Acute exposure to Helicobacter pylori causes cell damage and impairs the
      processes of cell migration and proliferation in cultured gastric mucosal cells
      in vitro. EGF-related growth factors play a major role in protecting gastric
      mucosa against injury, and are involved in the process of gastric mucosal
      healing. We therefore studied the acute effect of H. pylori on expression of EGF
      related growth factors and the proliferative response to these factors in gastric
      mucosal cells (MKN 28) derived from gastric adenocarcinoma. Exposure of MKN 28
      cells to H. pylori suspensions or broth culture filtrates upregulated mRNA
      expression of amphiregulin (AR) and heparin-binding EGF-like growth factor (HB
      EGF), but not TGFalpha. This effect was specifically related to H. pylori since
      it was not observed with E. coli, and was independent of VacA, CagA, PicA, PicB,
      or ammonia. Moreover, H. pylori broth culture filtrates stimulated extracellular
      release of AR and HB-EGF protein by MKN 28 cells. AR and HB-EGF dose-dependently
      and significantly stimulated proliferation of MKN 28 cells in the absence of H.
      pylori filtrate, but had no effect in the presence of H. pylori broth culture
      filtrates. Inhibition of AR- or HB-EGF- induced stimulation of cell growth was
      not mediated by downregulation of the EGF receptor since EGF receptor protein
      levels, EGF binding affinity, number of specific binding sites for EGF, or HB-EGF
      or AR-dependent tyrosine phosphorylation of the EGF receptor were not
      significantly altered by incubation with H. pylori broth culture filtrates.
      Increased expression of AR and HB-EGF were mediated by an H. pylori factor > 12
      kD in size, whereas antiproliferative effects were mediated by both VacA and a
      factor < 12 kD in size. We conclude that H. pylori increases mucosal generation
      of EGF-related peptides, but in this acute experimental model, this event is not
      able to counteract the inhibitory effect of H. pylori on cell growth. The
      inhibitory effect of H. pylori on the reparative events mediated by EGF-related
      growth factors might play a role in the pathogenesis of H. pylori-induced
      gastroduodenal injury.

PMID- 9541492
TI  - Apoptosis in insulin-secreting cells. Evidence for the role of intracellular Ca2+
      stores and arachidonic acid metabolism.
AB  - This study investigated the role of intracellular free Ca2+ concentration
      ([Ca2+]i) in apoptosis in MIN6 cells, an insulin secreting cell line, and in
      mouse islets. Thapsigargin, an inhibitor of sarcoendoplasmic reticulum Ca2+
      ATPases (SERCA), caused a time- and concentration-dependent decrease in the
      viability of MIN6 cells and an increase in DNA fragmentation and nuclear
      chromatin staining changes characteristic of apoptosis. Two structurally distinct
      SERCA inhibitors, cyclopiazonic acid and 2,5-di-[t-butyl]-1,4-hydroquinone also
      caused apoptosis, but agents that increased [Ca2+]i by other mechanisms did not
      induce apoptosis in MIN6 cells. Carbachol- or ionomycin-releasible intracellular
      Ca2+ stores were completely depleted in cells treated by SERCA inhibitors, but
      not by other agents that increase [Ca2+]i. The ability of thapsigargin to induce
      cell death was not affected by blocking Ca2+ influx or by clamping [Ca2+]i with a
      cytosolic Ca2+ buffer suggesting that the process did not depend on changes in
      [Ca2+]i per se. However, application of the lipoxygenase inhibitors 5,8,11
      eicosatrienoic acid and nordihydroguaiaretic acid partially prevented MIN6 cell
      apoptosis, while exposure of cells to the product of lipoxygenase, 12-hydroxy
      [5,8,10,14]-eicosatetraenoic acid, caused apoptosis. In contrast, inhibition of
      cyclooxygenase with indomethacin did not abolish thapsigargin-induced apoptosis
      in MIN6 cells. Our findings indicate that thapsigargin causes apoptosis in MIN6
      cells by depleting intracellular Ca2+ stores and leading to release of
      intermediate metabolites of arachidonic acid metabolism.

PMID- 9541493
TI  - Human beta-defensin-1: an antimicrobial peptide of urogenital tissues.
AB  - Antimicrobial peptides are widely distributed mediators of innate host defense in
      animals and plants. A 36 amino acid antimicrobial peptide belonging to the
      defensin family, and named human beta-defensin-1 (HBD-1), was purified recently
      from hemodialysate fluid, but its tissue sources were not identified. By Northern
      blotting, we found the highest concentrations of HBD-1 mRNA in the kidney and the
      female reproductive tract. In situ hybridization localized the HBD-1 mRNA in the
      epithelial layers of the loops of Henle, distal tubules, and the collecting ducts
      of the kidney and the epithelial layers of the vagina, ectocervix, endocervix,
      uterus, and fallopian tubes in the female reproductive tract. Using a novel
      technique designed to detect cationic peptides in urine, we recovered several
      forms of HBD-1 ranging in length from 36 to 47 amino acid (aa) residues and
      differing from each other by amino terminal truncation. The total concentration
      of HBD-1 forms in voided urine was estimated at 10-100 microg/liter, with
      individual variations in the total amount of HBD-1 peptides and the relative
      proportion of HBD-1 forms. Multiple forms of HBD-1 (size 36-47 aa) were also
      found in the blood plasma, bound to carrier macromolecules that released the
      peptide under acid conditions, and in vaginal mucosal secretions (39, 40, and 44
      aa). By immunostaining, HBD-1 was located in the kidney within the lumen of the
      loops of Henle, but no intracellular storage sites were identified in renal or
      female reproductive tissues. Recombinant HBD-1 forms (36, 39, and 42 aa) and
      natural HBD-1 forms were antimicrobial to laboratory and clinical strains of
      Escherichia coli at micromolar concentrations. HBD-1 activity was not changed
      appreciably by low pH, but was inhibited by high salt conditions. Some of the HBD
      1 peptides retained their activity against E. coli in unconcentrated (low
      conductance) urine, and the 36 aa form was microbicidal even in normal (high
      conductance) urine. Production of HBD-1 in the urogenital tract could contribute
      to local antimicrobial defense.

PMID- 9541494
TI  - Endogenous adenosine inhibits P-selectin-dependent formation of coronary
      thromboemboli during hypoperfusion in dogs.
AB  - The activation of platelets and the formation of neutrophil- platelet conjugates
      may lead to the development of thromboemboli. We studied whether blockade of
      adenosine receptors during coronary hypoperfusion may cause thromboemboli via P
      selectin-dependent mechanisms in 30 open-chest dogs. When coronary blood flow was
      reduced to 20% of the control, it was stable at low levels with increases in
      adenosine levels. When 8-p-sulfophenyltheophylline, an adenosine receptor
      antagonist, was infused during coronary hypoperfusion, coronary blood flow
      decreased gradually and approached almost zero 20 min after its administration.
      Histological examination revealed thromboemboli in the small coronary vessels.
      During hypoperfusion in the presence of 8-p-sulfophenyltheophylline, the mAb
      against P-selectin attenuated both the reduction in coronary blood flow and the
      formation of thromboemboli, and improved contractile and metabolic dysfunction of
      the myocardium. Flow cytometric analysis indicated that the expression of P
      selectin on platelet and neutrophil-platelet adhesion were increased during
      coronary hypoperfusion, and that both were further augmented by 8-p
      sulfophenyltheophylline. Immunohistochemical examination showed no staining of P
      selectin in the ischemic myocardium. Adenosine inhibited the thrombin-induced
      expression of P-selectin on platelet and neutrophil- platelet adhesion via
      adenosine A2 receptors. Adenosine appears to inhibit the formation of
      thromboemboli during coronary hypoperfusion by suppressing the expression of P
      selectin on platelets and neutrophil-platelet adhesion.

PMID- 9541496
TI  - Estradiol enhances thiazide-sensitive NaCl cotransporter density in the apical
      plasma membrane of the distal convoluted tubule in ovariectomized rats.
AB  - Recent data suggest that sex hormones affect the thiazide-sensitive NaCl
      cotransporter (TSC) density or binding capacity (Chen, Z., D.A. Vaughn, and D.D.
      Fanestil. 1994. J. Am. Soc. Nephrol. 5:1112-1119). Thus, we determined the effect
      of ovariectomy (OVX) and estrogen replacement on the ultrastructural localization
      of TSC in rat kidney using immunocytochemistry. Kidneys of intact female (CON)
      and OVX rats fed ad libitum for 6 and 9 wk or pair-fed for 9 wk were processed
      for transmission electron microscopy. Immunogold localization of rat TSC (rTSC1)
      demonstrated intense label in the apical plasma membrane of CON distal convoluted
      tubule (DCT). In OVX DCT, rTSC1 label and apical plasma membrane microprojections
      were decreased. Western blots of renal membrane protein from pair-fed CON and OVX
      revealed bands at 129-135 kD, but the OVX signal was reduced. Morphometric
      analyses demonstrated that injecting 10 microg/ kg body weight 17beta-estradiol
      subcutaneously 4x/wk in OVX rats restored DCT apical microprojections and label
      density for rTSC1. Thus, in OVX rats (a) rTSC1 immunoreactive renal membrane
      protein is reduced; (b) apical plasma membrane complexity and immunogold label
      for rTSC1 in DCT is decreased; and (c) estradiol replacement restores DCT
      ultrastructure and rTSC1 label to normal. We conclude that estrogen enhances the
      density of rTSC1 in the DCT, and may alter renal Na transport by this mechanism.

PMID- 9541495
TI  - Sympathetic activation in exercise is not dependent on muscle acidosis. Direct
      evidence from studies in metabolic myopathies.
AB  - Muscle acidosis has been implicated as a major determinant of reflex sympathetic
      activation during exercise. To test this hypothesis we studied sympathetic
      exercise responses in metabolic myopathies in which muscle acidosis is impaired
      or augmented during exercise. As an index of reflex sympathetic activation to
      muscle, microneurographic measurements of muscle sympathetic nerve activity
      (MSNA) were obtained from the peroneal nerve. MSNA was measured during static
      handgrip exercise at 30% of maximal voluntary contraction force to exhaustion in
      patients in whom exercise-induced muscle acidosis is absent (seven
      myophosphorylase deficient patients; MD [McArdle's disease], and one patient with
      muscle phosphofructokinase deficiency [PFKD]), augmented (one patient with
      mitochondrial myopathy [MM]), or normal (five healthy controls). Muscle pH was
      monitored by 31P-magnetic resonance spectroscopy during handgrip exercise in the
      five control subjects, four MD patients, and the MM and PFKD patients. With
      handgrip to exhaustion, the increase in MSNA over baseline (bursts per minute
      [bpm] and total activity [%]) was not impaired in patients with MD (17+/-2 bpm,
      124+/-42%) or PFKD (65 bpm, 307%), and was not enhanced in the MM patient (24
      bpm, 131%) compared with controls (17+/-4 bpm, 115+/-17%). Post-handgrip ischemia
      studied in one McArdle patient, caused sustained elevation of MSNA above basal
      suggesting a chemoreflex activation of MSNA. Handgrip exercise elicited an
      enhanced drop in muscle pH of 0.51 U in the MM patient compared with the decrease
      in controls of 0.13+/-0.02 U. In contrast, muscle pH increased with exercise in
      MD by 0.12+/-0.05 U and in PFKD by 0.01 U. In conclusion, patients with
      glycogenolytic, glycolytic, and oxidative phosphorylation defects show normal
      muscle sympathetic nerve responses to static exercise. These findings indicate
      that muscle acidosis is not a prerequisite for sympathetic activation in
      exercise.

PMID- 9541497
TI  - Phenotype-dependent differences in apolipoprotein E metabolism and in cholesterol
      homeostasis in human monocyte-derived macrophages.
AB  - In this study, we investigated the impact of the common apoE polymorphism on apoE
      metabolism and cholesterol homeostasis in monocyte-derived macrophages isolated
      from E2/2, E3/3, and E4/4 subjects. Unloaded cells of all genotypes contained
      similar amounts of free cholesterol, cholesteryl ester, and apoE mRNA. E3/3 cells
      secreted 77 and 30% more apoE than E2/2 or E4/4 cells, respectively. Pulse-chase
      studies confirmed that the apoE secretion rate was greatest in E3/3 and least in
      E2/2 cells and showed that a portion of apoE2, but not apoE3 or apoE4, was
      degraded intracellularly. Surface binding of apoE was greatest in E4/4 cells, as
      revealed by heparinase treatment. On cholesterol loading with acetylated LDL,
      apoE mRNA levels and protein secretion rose most in E4/4 and least in E2/2 cells.
      Cholesterol and cholesteryl ester content, however, rose most in E2/2 and least
      in E3/3 cells. Incubations with 3H-cholesterol-labeled acetylated LDL revealed
      that E2/2 cells were most efficient at secreting cholesterol. The greatest
      reuptake of 3H-cholesterol-rich particles was from E4/4 macrophage- conditioned
      media. Thus, E2/2 macrophages, despite a low apoE secretion rate, are protected
      from cholesterol storage by apoE-mediated cholesterol efflux. In E3/3
      macrophages, cholesterol accumulation is lessened by a high basal apoE secretion
      rate. E4/4 macrophages secrete the most apoE but lack effective net cholesterol
      efflux due to enhanced surface binding and reuptake of cholesterol-rich
      particles.

PMID- 9541498
TI  - Arthritis induced by proteoglycan aggrecan G1 domain in BALB/c mice. Evidence for
      t cell involvement and the immunosuppressive influence of keratan sulfate on
      recognition of t and b cell epitopes.
AB  - Our previous work showed that the proteoglycan aggrecan can induce erosive
      polyarthritis and spondylitis in BALB/c mice, and that the G1 domain of the
      proteoglycan aggrecan (G1) is the arthritogenic region. In this study, two T cell
      epitopes residing on G1 within residues 70-84 (peptide G5) and 150-169 (peptide
      G9) were identified using synthetic peptides and aggrecan-specific T cell lines.
      Two G1-specific T cell hybridomas exclusively responded to peptide G5. When the
      G5-specific T cell line was injected intraperitoneally into BALB/c mice, it
      induced acute inflammatory arthritis in joints, but only in those that had been
      injected with the epitope recognized by these T cells. Furthermore, we also
      demonstrate that the keratan sulfate chain(s) (KS) on G1 possess
      immunosuppressive properties with respect to T and B cell epitope recognition. T
      cell lines that recognize both G1 and peptide G5 show an increased response to G1
      after KS is removed. Antibodies in hyperimmune sera of mice immunized with G1
      show increased epitope recognition (quantitative and qualitative) after KS
      removal before immunization. These studies reveal that a T cell line specific to
      an epitope on the G1 domain of aggrecan, also recognizing a corresponding mouse
      G1 epitope, can induce arthritis by adoptive transfer and homing to the
      intraarticular epitope, thereby implicating T cells in arthritis development
      caused by immunity to the G1 domain of aggrecan. Moreover, the presence of KS on
      G1 can inhibit arthritis development by suppressing T and B cell epitope
      recognition.

PMID- 9541499
TI  - The HPV-activating cellular transcription factor Brn-3a is overexpressed in CIN3
      cervical lesions.
AB  - The cervical cellular transcription factors Brn-3a and Brn-3b have antagonistic
      effects on transcription of the human papilloma virus types 16 and 18 E6 and E7
      oncogenes, with Brn-3a activating expression and Brn-3b repressing it. We
      therefore measured expression of Brn-3a and Brn-3b mRNAs in biopsies from 16
      women with no detectable cervical abnormality, and in 14 women with cervical
      intraepithelial neoplasia grade 3 (CIN3) lesions. Although the mean level of Brn
      3b expression was similar in both groups, the mean level of Brn-3a expression was
      over 300-fold higher in the CIN3 samples when compared with normals. Elevated
      expression of Brn-3a was also detected in 16 histologically normal regions of the
      cervix adjacent to the CIN3 lesions, indicating that elevation of Brn-3a levels
      is not confined to the lesion in women with CIN3, and is thus not a consequence
      of the oncogenic process. The elevated levels of Brn-3a in the CIN3 patient
      samples, together with the activating effect of Brn-3a on HPV-16 and -18 oncogene
      expression, suggest that induction of this factor is involved in activating HPV
      16 and -18 oncogene expression in the cervix, and hence in the production of
      cervical cancers induced by HPV.

PMID- 9541500
TI  - MIP-1alpha as a critical macrophage chemoattractant in murine wound repair.
AB  - At sites of injury, macrophages secrete growth factors and proteins that promote
      tissue repair. While this central role of the macrophage has been well studied,
      the specific stimuli that recruit macrophages into sites of injury are not well
      understood. This study examines the role of macrophage inflammatory protein
      1alpha (MIP-1alpha), a C-C chemokine with monocyte chemoattractant capability, in
      excisional wound repair. Both MIP-1alpha mRNA and protein were detectable in
      murine wounds from 12 h through 5 d after injury. MIP-1alpha protein levels
      peaked 3 d after injury, coinciding with maximum macrophage infiltration. The
      contribution of MIP-1alpha to monocyte recruitment into wounds was assessed by
      treating mice with neutralizing anti-MIP-1alpha antiserum before injury. Wounds
      of mice treated with anti-MIP-1alpha antiserum had significantly fewer
      macrophages than control (41% decrease, P < 0. 01). This decrease in wound
      macrophages was paralleled by decreased angiogenic activity and collagen
      synthesis. When tested in the corneal micropocket assay, wound homogenates from
      mice treated with anti-MIP-1alpha contained significantly less angiogenic
      activity than control wound homogenates (27% positive for angiogenic activity
      versus 91% positive in the control group, P < 0.01). Collagen production was also
      significantly reduced in the wounds from anti-MIP-1alpha treated animals (29%
      decrease, P < 0.05). The results demonstrate that MIP-1alpha plays a critical
      role in macrophage recruitment into wounds, and suggest that appropriate tissue
      repair is dependent upon this recruitment.

PMID- 9541501
TI  - The full induction of human apoprotein A-I gene expression by the experimental
      nephrotic syndrome in transgenic mice depends on cis-acting elements in the
      proximal 256 base-pair promoter region and the trans-acting factor early growth
      response factor 1.
AB  - To identify molecular factors regulating apo A-I production in vivo, we induced
      in transgenic mice the experimental nephrotic syndrome, which results in elevated
      levels of HDL cholesterol (HDL-C), plasma apo A-I, and hepatic apo A-I mRNA.
      Human (h) apo A-I transgenic mice with different length 5' flanking sequences
      (5.5 or 0.256 kb, the core promoter for hepatic-specific basal expression) were
      injected with nephrotoxic (NTS) or control serum. With nephrosis, there were
      comparable (greater than twofold) increases in both lines of HDL-C, h-apo A-I,
      and hepatic h-apo A-I mRNA, suggesting that cis-acting elements regulating
      induced apo A-I gene expression were within its core promoter. Hepatic nuclear
      extracts from control and nephrotic mice footprinted the core promoter similarly,
      implying that the same elements regulated basal and induced expression. Hepatic
      mRNA levels for hepatocyte nuclear factor (HNF) 4 and early growth response
      factor (EGR) 1, trans-acting factors that bind to the core promoter, were
      measured: HNF4 mRNA was not affected, but that of EGR-1 was elevated
      approximately fivefold in the nephrotic group. EGR-1 knockout (EGR1-KO) mice or
      mice expressing EGR-1 were injected with either NTS or control serum. Levels of
      HDL-C, apo A-I, and hepatic apo A-I mRNA were lowest in nonnephrotic EGR1-KO mice
      and highest in nephrotic mice expressing EGR-1. Although in EGR1-KO mice HDL-C,
      apo A-I, and apo A-I mRNA levels also increased after NTS injection, they were
      approximately half of those in the nephrotic EGR-1-expressing mice. We conclude
      that in this model, basal and induced apo A-I gene expression in vivo are
      regulated by the trans-acting factor EGR-1 and require the same cis-acting
      elements in the core promoter.

PMID- 9541502
TI  - Hyaluronic acid capsule modulates M protein-mediated adherence and acts as a
      ligand for attachment of group A Streptococcus to CD44 on human keratinocytes.
AB  - We used wild-type and isogenic mutant strains of group A Streptococcus (GAS) that
      expressed M protein, capsule, or both to study the function of M protein and the
      hyaluronic acid capsular polysaccharide in attachment of GAS to human
      keratinocytes. Types 6 and 24, but not type 18, M protein were found to mediate
      attachment of GAS to soft palate or skin keratinocytes, but this interaction was
      prevented by the hyaluronic acid capsule on highly encapsulated, or mucoid,
      strains. Monoclonal antibody to CD44, the principal hyaluronic acid-binding
      receptor on keratinocytes, inhibited attachment of both highly encapsulated and
      poorly encapsulated wild type strains of GAS, but not the attachment of acapsular
      mutants. Transfection of K562 cells with cDNA encoding human CD44 conferred the
      capacity to bind each of six wild-type strains of GAS, but not to bind acapsular
      mutants. Because, in contrast to other potential adhesins, the group A
      streptococcal capsule is both highly conserved and surface-exposed, it may serve
      as a universal adhesin for attachment of diverse strains of GAS to keratinocytes
      of the pharyngeal mucosa and the skin.

PMID- 9541503
TI  - Hypercholesterolemia is associated with a T helper (Th) 1/Th2 switch of the
      autoimmune response in atherosclerotic apo E-knockout mice.
AB  - Atherosclerosis is an inflammatory-fibrotic response to accumulation of
      cholesterol in the artery wall. In hypercholesterolemia, low density lipoproteins
      (LDL) accumulate and are oxidized to proinflammatory compounds in the arterial
      intima, leading to activation of endothelial cells, macrophages, and T
      lymphocytes. We have studied immune cell activation and the autoimmune response
      to oxidized LDL in atherosclerotic apo E-knockout mice. Autoantibodies to
      oxidized LDL exhibited subclass specificities indicative of T cell help, and the
      increase in antibody titers in peripheral blood was associated with increased
      numbers of cytokine-expressing T cells in the spleen. In addition to T cell
      dependent antibodies, IgM antibodies to oxidized LDL were also increased in apo E
      knockout mice. This suggests that both T cell-dependent and T cell-independent
      epitopes may be present on oxidized LDL. In moderate hypercholesterolemia, IgG
      antibodies were largely of the IgG2a isotype, suggesting that T cell help was
      provided by proinflammatory T helper (Th) 1 cells, which are prominent components
      of atherosclerotic lesions. In severe hypercholesterolemia induced by cholesterol
      feeding of apo E-knockout mice, a switch to Th2-dependent help was evident. It
      was associated with a loss of IFN-gamma-producing Th1 cells in the spleen,
      whereas IL-4-producing Th2 cells were more resistant to hypercholesterolemia. IFN
      gamma but not IL-4 mRNA was detected in atherosclerotic lesions of moderately
      hypercholesterolemic apo E-knockout mice, but IL-4 mRNA appeared in the lesions
      when mice were made severely hypercholesterolemic by cholesterol feeding. These
      data show that IFN-gamma-producing Th1 cells infiltrate atherosclerotic lesions
      and provide T cell help for autoimmune responses to oxidized LDL in apo E
      knockout mice. However, severe hypercholesterolemia is associated with a switch
      from Th1 to Th2, which results not only in the formation of IgG1 autoantibodies
      to oxidized LDL, but also in the appearance of Th2-type cytokines in the
      atherosclerotic lesions. Since the two subsets of T cells counteract each other,
      this switch may have important consequences for the inflammatory/immune process
      in atherosclerosis.

PMID- 9541505
TI  - Reproduction of human fibrous dysplasia of bone in immunocompromised mice by
      transplanted mosaics of normal and Gsalpha-mutated skeletal progenitor cells.
AB  - We have isolated progenitor cells from the stromal system of the fibrous
      dysplastic marrow of patients with McCune-Albright Syndrome. Analysis of the
      Gsalpha gene from individual colonies provided direct evidence for the presence
      of two different genotypes within single fibrous dysplastic lesions: marrow
      stromal cells containing two normal Gsalpha alleles, and those containing one
      normal allele and an allele with an activating mutation. Transplantation of
      clonal populations of normal cells into the subcutis of immunocompromised mice
      resulted in normal ossicle formation. In contrast, transplantation of clonal
      populations of mutant cells always led to the loss of transplanted cells from the
      transplantation site and no ossicle formation. However, transplantation of a
      mixture of normal and mutant cells reproduced an abnormal ectopic ossicle
      recapitulating human fibrous dysplasia and providing an in vivo cellular model of
      this disease. These results provide experimental evidence for the necessity of
      both normal and mutant cells in the development of McCune-Albright Syndrome
      fibrous dysplastic lesions in bone.

PMID- 9541504
TI  - Hepatic apo E expression is required for remnant lipoprotein clearance in the
      absence of the low density lipoprotein receptor.
AB  - According to the secretion-capture model of remnant lipoprotein clearance, apo E
      secreted by hepatocytes into the space of Disse serves to enrich the remnants
      with a ligand for receptor-mediated lipoprotein endocytosis. Current evidence
      supports a two-receptor model of lipoprotein removal, in which apo E-containing
      remnants bind either the low density lipoprotein receptor (LDLR) or the LDLR
      related protein (LRP). Recently, we demonstrated that reconstitution of apo E(-/
      ) mice with apo E(+/+) marrow results in normalization of plasma lipoprotein
      levels, indicating that hepatic expression of apo E is not required for remnant
      clearance and calling into question the relevance of the secretion-capture
      mechanism. To dissect the relative contributions of LDLR and LRP to the cellular
      catabolism of remnant lipoproteins by the hepatocyte, bone marrow transplantation
      (BMT) was used to reconstitute macrophage expression of apo E in mice that were
      null for expression of both apo E and the LDLR. Reconstitution of macrophage apo
      E in apo E(-/-)/LDLR(-/-) mice had no effect on serum lipid and lipoprotein
      concentrations, although it produced plasma apo E levels up to 16-fold higher
      than in C57BL/6 controls. Immunocytochemistry of hepatic sections revealed
      abundant staining for apo E in the space of Disse, but no evidence of receptor
      mediated endocytosis of remnant lipoproteins. Transient expression of human LDLR
      in the livers of apo E(+/+)--> apo E(-/-)/LDLR(-/-) mice by adenoviral gene
      transfer resulted in normalization of serum lipid levels and in the clearance of
      apo E-containing lipoproteins from the space of Disse. We conclude that whereas
      the LDLR efficiently clears remnant lipoproteins irrespective of the site of
      origin of apo E, endocytosis by the chylomicron remnant receptor (LRP) is
      absolutely dependent on hepatic expression of apo E. These data demonstrate in
      vivo the physiologic relevance of the apo E secretion-capture mechanism in the
      liver.

PMID- 9541506
TI  - The role of antibodies in acute vascular rejection of pig-to-baboon cardiac
      transplants.
AB  - Long-term success in xenotransplantation is currently hampered by acute vascular
      rejection. The inciting cause of acute vascular rejection is not yet known;
      however, a variety of observations suggest that the humoral immune response of
      the recipient against the donor may be involved in the pathogenesis of this
      process. Using a pig-to-baboon heterotopic cardiac transplant model, we examined
      the role of antibodies in the development of acute vascular rejection. After
      transplantation into baboons, hearts from transgenic pigs expressing human decay
      accelerating factor and CD59 underwent acute vascular rejection leading to graft
      failure within 5 d; the histology was characterized by endothelial injury and
      fibrin thrombi. Hearts from the transgenic pigs transplanted into baboons whose
      circulating antibodies were depleted using antiimmunoglobulin columns (Therasorb,
      Unterschleisshein, Germany) did not undergo acute vascular rejection in five of
      six cases. Biopsies from the xenotransplants in Ig-depleted baboons revealed
      little or no IgM or IgG, and no histologic evidence of acute vascular rejection
      in the five cases. Complement activity in the baboons was within the normal range
      during the period of xenograft survival. In one case, acute vascular rejection of
      a xenotransplant occurred in a baboon in which the level of antidonor antibody
      rose after Ig depletion was discontinued. This study provides evidence that
      antibodies play a significant role in the pathogenesis of acute vascular
      rejection, and suggests that acute vascular rejection might be prevented or
      treated by therapies aimed at the humoral immune response to porcine antigens.

PMID- 9541507
TI  - An autosomal genomic scan for loci linked to prediabetic phenotypes in Pima
      Indians.
AB  - Type 2 diabetes mellitus is a common chronic disease that is thought to have a
      substantial genetic basis. Identification of the genes responsible has been
      hampered by the complex nature of the syndrome. Abnormalities in insulin
      secretion and insulin action predict the development of type 2 diabetes and are,
      themselves, highly heritable traits. Since fewer genes may contribute to these
      precursors of type 2 diabetes than to the overall syndrome, such genes may be
      easier to identify. We, therefore, undertook an autosomal genomic scan to
      identify loci linked to prediabetic traits in Pima Indians, a population with a
      high prevalence of type 2 diabetes. 363 nondiabetic Pima Indians were genotyped
      at 516 polymorphic microsatellite markers on all 22 autosomes. Linkage analyses
      were performed using three methods (single-marker, nonparametric multipoint
      [MAPMAKER/SIBS], and variance components multipoint). These analyses provided
      evidence for linkage at several chromosomal regions, including 3q21-24 linked to
      fasting plasma insulin concentration and in vivo insulin action, 4p15-q12 linked
      to fasting plasma insulin concentration, 9q21 linked to 2-h insulin concentration
      during oral glucose tolerance testing, and 22q12-13 linked to fasting plasma
      glucose concentration. These results suggest loci that may harbor genes
      contributing to type 2 diabetes in Pima Indians. None of the linkages exceeded a
      LOD score of 3.6 (a 5% probability of occurring in a genome-wide scan). These
      findings must, therefore, be considered tentative until extended in this
      population or replicated in others.

PMID- 9541508
TI  - Expression of the human histocompatibility leukocyte antigen DR3 transgene
      reduces the severity of demyelination in a murine model of multiple sclerosis.
AB  - The role of various MHC genes in determining the progression of multiple
      sclerosis (MS) remains controversial. The HLA-DR3 gene has been associated with
      benign relapsing MS in some genetic epidemiologic studies, but with disease
      progression in others. We induced demyelination in highly susceptible B10.M and
      B10.Q mice expressing the DR3 (HLA-DRB1*0301) transgene to determine directly the
      effects of a human transgene by infecting them with Theiler's murine
      encephalomyelitis virus (TMEV). DR3+ mice experienced a dramatic reduction in the
      extent and severity of demyelination compared with DR3- littermate controls,
      whereas anti-TMEV antibody titers, delayed-type hypersensitivity responses, and
      levels of infectious virus, virus antigen, and virus RNA were similar in both
      groups. To address a possible mechanism of how the human transgene is reducing
      virus-induced demyelination, we analyzed cytokine expression in the lesions and
      also determined whether B10.M mice can respond to peptides derived from the DR3
      molecule. Intense staining for IFN-gamma and IL-4, T helper (TH) 1 and TH2
      cytokines, respectively, was found in the lesions of TMEV-infected DR3- mice but
      not in the DR3+ transgenic mice at day 21 after infection. DR3 peptides elicited
      strong proliferative responses in B10.M mice but not in B10.M (DR3+) mice. These
      experiments are the first to demonstrate that a human class II DR gene can alter
      the severity of demyelination in an animal model of MS without influencing viral
      load. These experiments are consistent with a mechanism by which DR3 reduces
      demyelination by altering the cytokine expression in the lesions, possibly by
      deleting T cells involved in virus-induced pathology.

PMID- 9541509
TI  - Diastolic dysfunction and altered energetics in the alphaMHC403/+ mouse model of
      familial hypertrophic cardiomyopathy.
AB  - An arginine to glutamine missense mutation at position 403 of the beta-cardiac
      myosin heavy chain causes familial hypertrophic cardiomyopathy. Here we study
      mice which have this same missense mutation (alphaMHC403/+) using an isolated,
      isovolumic heart preparation where cardiac performance is measured simultaneously
      with cardiac energetics using 31P nuclear magnetic resonance spectroscopy. We
      observed three major alterations in the physiology and bioenergetics of the
      alphaMHC403/+ mouse hearts. First, while there was no evidence of systolic
      dysfunction, diastolic function was impaired during inotropic stimulation.
      Diastolic dysfunction was manifest as both a decreased rate of left ventricular
      relaxation and an increase in end-diastolic pressure. Second, under baseline
      conditions alphaMHC403/+ hearts had lower phosphocreatine and increased inorganic
      phosphate contents resulting in a decrease in the calculated value for the free
      energy released from ATP hydrolysis. Third, hearts from alphaMHC403/+ hearts that
      were studied unpaced responded to increased perfusate calcium by decreasing heart
      rate approximately twice as much as wild types. We conclude that hearts from
      alphaMHC403/+ mice demonstrate work load-dependent diastolic dysfunction
      resembling the human form of familial hypertrophic cardiomyopathy. Changes in
      high-energy phosphate content suggest that an energy-requiring process may
      contribute to the observed diastolic dysfunction.

PMID- 9541510
TI  - Hypertension, hypertriglyceridemia, and impaired endothelium-dependent vascular
      relaxation in mice lacking insulin receptor substrate-1.
AB  - Insulin resistance is often associated with atherosclerotic diseases in subjects
      with obesity and impaired glucose tolerance. This study examined the effects of
      insulin resistance on coronary risk factors in IRS-1 deficient mice, a nonobese
      animal model of insulin resistance. Blood pressure and plasma triglyceride levels
      were significantly higher in IRS-1 deficient mice than in normal mice. Impaired
      endothelium-dependent vascular relaxation was also observed in IRS-1 deficient
      mice. Furthermore, lipoprotein lipase activity was lower than in normal mice,
      suggesting impaired lipolysis to be involved in the increase in plasma
      triglyceride levels under insulin-resistant conditions. Thus, insulin resistance
      plays an important role in the clustering of coronary risk factors which may
      accelerate the progression of atherosclerosis in subjects with insulin
      resistance.

PMID- 9541511
TI  - In vivo human carboxylesterase cDNA gene transfer to activate the prodrug CPT-11
      for local treatment of solid tumors.
AB  - To evaluate the concept that in vivo transfer of the human carboxylesterase gene
      will confer sensitivity of a solid tumor to the prodrug CPT-11 (irinotecan), we
      constructed an adenovirus vector (AdCMV.CE) carrying the human carboxylesterase
      gene driven by the cytomegalovirus (CMV) promoter, infected A549 human lung
      adenocarcinoma cells in vitro and in vivo, and evaluated cell growth over time.
      AdCMV.CE produced a functional carboxylesterase protein in A549 cells in vitro
      and in vivo as evidenced by ability of lysates from the infected cells to convert
      CPT-11 to its active metabolite SN-38. The AdCMV.CE vector effectively suppressed
      A549 cell growth in vitro in the presence of CPT-11. Cell mixing studies
      demonstrated that when as few as 10% of cells expressed the human
      carboxylesterase gene, there was bystander growth suppression in the presence of
      CPT-11. Consistent with these in vitro observations, when AdCMV.CE was directly
      injected into established subcutaneous A549 tumors in nude mice receiving CPT-11,
      there was 35% reduction in tumor size at day 27 compared to controls, and a 41%
      reduction at day 34 (P < 0.01, both comparisons to controls). Similar
      observations were made with the cell line H157 and HeLa. These observations
      suggest that local gene transfer of the human carboxylesterase gene and
      concomitant local administration of CPT-11 may have potential as a strategy for
      control of the growth of solid tumors.

PMID- 9541514
TI  - Measurement of forearm bone mineral density: comparison of precision of five
      different instruments.
AB  - Measurement of bone mineral density (BMD) is used for clinical estimation of
      fracture risk in osteoporosis. The precision of the method is important for the
      evaluation of true and clinical relevant changes in BMD in patients with
      osteoporosis. We measured BMD of the forearm in 14 young, healthy probands (10
      males, 4 females), aged 24. 6 +/- 1.5 years with five different instruments using
      dual-energy X-ray absorptiometry (DXA), single-photon absorptiometry (SPA), and
      peripheral quantitative computed tomography (pQCT). Precision was expressed as
      the percentage coefficient of variation (CV%). In addition, the standardized CV%
      (sCV%) and the root mean square standard deviation (rmsSD%) was calculated for
      long-term precision. CV% ranged from 1.04 (SPA, distal BMD) to 2.75% (pQCT,
      trabecular BMD) for short-term precision and from 1.49 (DXA, QDR 1000, 1/3-distal
      BMD) to 4.33% (SPA, ultradistal) for long-term precision, respectively. The
      results for the rmsSD% were higher but correlated well with the CV%. A change
      that exceeds 2 radical2 CV% has been considered as being significant. On this
      basis, 24.0 +/- 5.1% (mean +/- SEM) of the participants in our study would be
      expected to have a significant change in BMD without any correlation to the time
      delay between the two measurements. Measurements of BMD were done at two
      locations with all five instruments: ultradistal and middistal BMD using DXA and
      SPA and total and trabecular BMD using pQCT, respectively. Coefficients of
      correlation for "between-instrumental" correlation were greater than 0.5 for
      almost all instruments. Distal and ultradistal BMD measured by SPA and trabecular
      and total BMD measured by pQCT correlated better with ultradistal BMD measured by
      DXA. Correspondingly, "within-instrumental" correlation was better for pQCT and
      SPA than for DXA. The coefficients of correlation between the different DXA
      methods were greater than 0.95 when corresponding locations were compared. We
      conclude that the clinical value of monitoring bone loss by measurement of
      forearm BMD is compromised by the low precision which was seen for DXA methods as
      well as for SPA and even pQCT in young healthy controls.

PMID- 9541512
TI  - Regulation of experimental autoimmune encephalomyelitis with insulin-like growth
      factor (IGF-1) and IGF-1/IGF-binding protein-3 complex (IGF-1/IGFBP3).
AB  - Insulin-like growth factor (IGF)-1 is a cytokine that promotes oligodendrocyte
      development and myelin production. This study investigated whether treatment of
      chronic, relapsing murine experimental autoimmune encephalomyelitis (EAE) with
      IGF-1 or IGF-1 associated with its binding protein, IGFBP3, altered the course of
      disease. Administration of IGF-1/IGFBP3 (1-100 mg/kg per day) delayed the onset
      of disease in a dose-dependent manner and histologic examination showed a delay
      in inflammatory cells entering the central nervous system. However, once signs of
      EAE developed, disease was enhanced in the mice that had been given the highest
      dose of IGF-1/IGFBP3. Treatment with IGF-1/IGFBP3 after the onset of signs
      resulted in a severe relapse. Administration of free IGF-1 (10 mg/kg per day)
      provided mild protection when given before disease onset, but did not
      significantly alter the course of disease if given after disease onset. Possible
      mechanisms that could explain the altered disease in IGF-1/IGFBP3-treated mice
      included (a) IGF-1/IGFBP3 administration delayed the onset of EAE by
      downregulating ICAM-1 gene expression in the central nervous system, and (b) IGF
      1/IGFBP3 treatment of EAE resulted in more severe disease due to enhanced
      expansion of encephalitogenic T cells. Although IGF-1 may enhance remyelination,
      these results indicate that administration of IGF-1 associated with IGFBP3 may
      also accentuate autoimmune demyelinating disease.

PMID- 9541513
TI  - Suppression of bone resorption in early postmenopausal women by intranasal salmon
      calcitonin in relation to dosage and basal bone turnover.
AB  - In the present study, we assessed the ability of increasing doses of intranasal
      calcitonin to suppress urinary deoxypyridinoline cross-link (DPD), a specific
      biochemical marker of bone resorption, in early postmenopausal women. Subjects
      consisted of 30 healthy Thai women within 5 years of postmenopause, randomly
      assigned to 50, 100, or 200 IU of intranasal calcitonin 5 days/week for 3 months.
      Calcium supplementation by calcium carbonate capsules at 750 mg of elemental
      calcium per day was given to all subjects. Twenty four-hour urine for DPD and
      creatinine assays was collected at baseline, 1 month, and 3 months after
      treatment. All DPD values were corrected with urinary creatinine before analyses.
      Data were expressed as mean +/- SEM. DPD decreased significantly 1 month after
      intranasal calcitonin treatment (P < 0.01). However, at 3 months, DPD increased
      when compared with the values at 1 month (P < 0.01), suggesting that there may be
      a reduction in the suppression of bone resorption after prolonged calcitonin
      therapy. Using a stepwise multiple regression model to address whether dosage and
      DPD at baseline influence the response to intranasal calcitonin, it was found
      that DPD suppression after intranasal calcitonin was not related to dosage but
      was strongly associated with baseline DPD (P < 0.0001). Suppression of bone
      resorption in early postmenopausal women by intranasal calcitonin is determined
      more by the state of bone turnover at baseline than the dosage of calcitonin.

PMID- 9541515
TI  - Association between female sex hormones and biochemical markers of bone turnover
      in peri- and postmenopausal women.
AB  - In an epidemiological study, markers of bone formation (serum osteocalcin and C
      terminal propeptide of type I collagen) and bone resorption [urinary type I
      collagen peptides (Crosslaps), urinary total pyridinoline (TPYRI), urinary
      deoxypyridinoline (DPYRI) as well as female sex hormones (serum estradiol)],
      follicle-stimulating hormone (FSH) and luteinizing hormone were measured in 237
      women. This cohort aged 44-66 years, came for their first medical examination
      since menopause to the outpatient menopause clinic at the Kaiser-Franz-Josef
      Hospital, Vienna. The women were all 0.5-5.0 years since cessation of menses and
      were not taking medications other than hormone replacement therapy [52 cases,
      21.9%)] and had no diseases known to affect bone and mineral metabolism. The best
      correlation was found between urinary DPYRI and urinary TPYRI (r = 0. 63, P =
      0.0001), followed by urinary Crosslaps and urinary DPYRI (r = 0.47, p = 0.0001).
      Only weak but significant correlations between E2 and urinary Crosslaps (r = 
      0.21, P < 0.0001) as well as serum E2 and serum osteocalcin (r = -0.16, P =
      0.0007), were observed. Of the 237 women 53% suffered from a severe E2 deficiency
      (E2 < 10.0 ng/liter). In these patients, urinary Crosslaps (+48%) and serum
      osteocalcin (+22%) were significantly higher (P < 0.0001) compared with those
      patients with E2 levels > 10 ng/liter. Women with E2 levels >10 ng/liter were
      further subdivided into those with and without sex hormone replacement therapy,
      whereby no statistical differences in any of the biochemical markers could be
      observed between these groups. We could clearly demonstrate that in
      postmenopausal women suffering from severe E2 deficiency (E2 < 10 ng/liter),
      urinary Crosslaps and serum osteocalcin are significantly increased, indicating
      in principle a clear correlation between E2 deficiency and these markers of bone
      turnover.

PMID- 9541516
TI  - Differences in bone resorption after menopause in Japanese women with normal or
      low bone mineral density: quantitation of urinary cross-linked N-telopeptides.
AB  - The objective of this study was to examine the value of NTx, a urinary cross
      linked N-telopeptides of type I collagen, as a marker of bone resorption. We
      assessed changes in pre- and postmenopausal bone resorption by evaluating the
      correlation of NTx with L2-4 bone mineral density (BMD) in a total of 1100
      Japanese women, aged 19-80 years [272 premenopausal (45.2 +/- 6.2 years) and 828
      postmenopausal (59.5 +/- 6.2 years)]. Postmenopausal women were divided into
      three groups based on the range of BMD (normal, osteopenic, and osteoporotic).
      Within each group, subjects were further segregated according to years since
      menopause (YSM). NTx values were then evaluated for each group. Our results
      showed that BMD was significantly decreased (P < 0.05) and NTx was significantly
      increased (P < 0.01) after menopause in age-matched analysis. Consistent with a
      previous report, NTx was inversely correlated with BMD for the entire cohort of
      study subjects (r = -0.299), although NTx correlated better with premenopausal
      than postmenopausal BMD (r = -0.240 versus r = -0.086). This may have been due to
      the fact that elevated values of NTx were exhibited over the entire range of BMD
      present in the postmenopausal women, suggesting that NTx might respond faster to
      the estrogen withdrawal than BMD. In all postmenopausal women, regardless of the
      range of BMD, the increase in NTx reached a peak within 5 YSM. After 11 YSM,
      however, NTx remained elevated in the osteoporotic group but it decreased in the
      osteopenic group, and showed no significant change in the group of postmenopausal
      women with normal BMD. These findings suggest that bone resorption is
      dramatically increased within 5 years after menopause but remains increased only
      in osteoporotic women.

PMID- 9541517
TI  - Relationships between bone mass measurements and lifetime physical activity in a
      Swedish population.
AB  - Lifetime occupational and leisure time activities were assessed by a
      questionnaire in order to evaluate their relationship to bone mass measurements
      and biochemical markers of bone metabolism in a population of 61 women and 61
      men, randomly selected from a Swedish population register, to represent ages
      between 22 and 85 years. We also considered possible confounders by using
      questions about smoking habits, milk consumption, hormone replacement therapy
      (HRT), and menopausal age. Bone mineral density (BMD) and bone mineral content
      (bone mass, BMC) of the total body, lumbar spine, and proximal femur (neck,
      trochanter, Ward's triangle) were measured by dual energy X-ray absorptiometry
      (DXA), and BMD of the forearm with single energy X-ray absorptiometry (SXA). In
      addition, both DXA and SXA provided information on bone area. Quantitative
      ultrasound measurements (QUS) at the heel were performed to assess the speed of
      sound (SOS) and broadband ultrasound attenuation (BUA). Fasting blood samples
      were analyzed for biochemical markers of bone metabolism as well as parathyroid
      hormone (PTH) and total serum calcium. After adjustment for confounding factors,
      neither BMD nor QUS measurements were consistently related to lifetime leisure
      time or occupational activities; nor were there any consistent patterns relating
      biochemical markers of bone metabolism to bone mass measurements. However,
      physical activity seemed to influence bone mass, area, and width more than
      density. In men, high levels of leisure time activity were associated with raised
      values for lumbar spine area (6.2%) and width (3.3%) as well as for femoral neck
      area (5.5%) compared with their low activity counterpart. Men exposed to high
      levels of occupational activity demonstrated lower lumbar spine BMD (10.9%) and
      area (5.3%) than men with low activity levels. Within an unselected Swedish
      population, estimation of lifetime occupational and sport activities as well as
      bedrest, using a questionnaire, demonstrated no major effects on bone density.
      However, the association between high levels of lifetime activity and raised
      values for bone mass, area, and width indicate that geometrical changes in bone
      may provide better estimations of mechanically induced bone strength than bone
      density, at least in men.

PMID- 9541518
TI  - Vitamin D receptor alleles and bone's response to physical activity.
AB  - The objective of this prospective controlled study was to determine whether the
      osteogenic response of bone to mechanical loading is dependent on the vitamin D
      receptor (VDR) polymorphism. Thirty-five healthy premenopausal women took part in
      a progressive, high-impact exercise three times a week for a period of 18 months
      and 45 women served as nonexercising controls. The trainees were divided into
      three groups: bb (n = 12, 34%); Bb (n = 16, 46%); BB (n = 7, 20%) according to
      polymorphism at the gene encoding the VDR (BB representing subjects without the
      restriction enzyme BsmI sites on the two VDR gene alleles). Bone mineral content
      (BMC) and areal bone mineral density (BMD) were measured at the lumber spine,
      proximal femur, knee, calcaneus, and dominant distal radius before the beginning
      of the exercise regimen and at 12 and 18 months of training using dual-energy x
      ray absorptiometry (DXA). As an indicator of the total osteogenic effect of the
      training, SigmaBMC was derived by summing up the BMC values of the loaded sites
      (i.e., the lower limb sites and the lumbar spine). The mean SigmaBMC increased
      2.0% in the bb group, 3.0% in the Bb group, and 2.8% in the BB group (P = 0.184
      for the intergroup difference), but only 0. 8% in the controls (exercisers versus
      controls, P < 0.001). Individuals with the BB genotype of the VDR gene, subjects
      with whom the BMC can be lower than normal and whose bones can be less responsive
      to pharmacological therapies than bones of the other individuals, seem to have as
      good osteogenic response to mechanical loading as subjects with other VDR
      genotypes. Thus, irrespective of the VDR genotype, physical activity seems to be
      beneficial for bones of premenopausal women.

PMID- 9541519
TI  - Mitogenic action of adenosine on osteoblast-like cells, MC3T3-E1.
AB  - The purpose of this study was to investigate the mechanisms by which adenosine
      stimulates proliferation of osteoblast-like cells, MC3T3-E1. Adenosine by itself
      induces the stimulation of cell proliferation and accentuates the mitogenecity of
      PDGFs (AA and BB homodimers) for the cells. 8-Cyclopentyl-1,3-dimethylxanthine
      (CPX), a nonselective adenosine receptor antagonist, partially inhibited
      adenosine-induced DNA synthesis in a competitive manner, suggesting that the
      mitogenic action of adenosine is, at least in part, mediated by xanthine
      sensitive receptors. In pertussis-toxin (PTX)-pretreated cells, adenosine- but
      not PDGF-BB-stimulated DNA synthesis was partially inhibited, and CPX did not
      exert a further inhibitory effect, suggesting an involvement of PTX-sensitive G
      protein downstream of CPX-sensitive receptor. When adenosine uptake was prevented
      with dipyridamole, the stimulation of proliferation by adenosine was not
      decreased at all, indicating that the CPX-insensitive part of adenosine action is
      not associated with the uptake of adenosine and subsequent incorporation into the
      nucleotide pool. Adenosine did not influence the basal level or the PDGF-BB
      induced increase in [Ca2+]i. Since it is known that the cAMP pathway acts in
      inhibiting osteoblast proliferation, the mitogenic action of adenosine would be
      dependent on neither the cAMP pathway nor the phospholipase C/Ca2+ pathway. It
      has been concluded that adenosine exerts a mitogenic effect via two pathways at
      least, one mediated by xanthine-sensitive receptor and PTX-sensitive G-protein
      and the other through an unknown xanthine- and PTX-insensitive process.

PMID- 9541520
TI  - Regional variations in the progression of bone loss in two different mouse
      osteopenia models.
AB  - Differences in trabecular and cortical bone loss have been demonstrated
      clinically, but differences in bone loss at different skeletal sites remain
      unclear. We examined regional variations in bone loss histomorphometrically in
      two strains of mice in which osteopenia progresses spontaneously: tiptoe-walking
      Yoshimura (twy) mice (from 4 to 37 weeks of age) and senescent ICR mice (from 4
      to 88 weeks of age). Morphometrical measurements were obtained to investigate the
      changes with age in trabecular bone area and anterior cortical bone width in the
      lumbar vertebral body, trabecular bone area in the tibia, bone area in the
      parietal bone, and the cortical index in the humerus. Results showed that, in twy
      mice, trabecular turnover was higher than in ICR mice, and bone loss progressed
      in the following order: tibial trabecular bone, lumbar trabecular bone, parietal
      bone, lumbar anterior cortical bone, and the humerus. In ICR mice, bone formation
      declined after 60 weeks. Bone loss progressed in tibial trabecular bone and the
      parietal bone at 60 weeks of age, followed by lumbar trabecular bone, lumbar
      anterior cortical bone, and the humerus at 88 weeks of age. Bone loss varied at
      each site and between the two mouse strains, with different bone turnover rates.
      The findings of the present study indicate that special attention should be paid
      to regional variations in the progression of bone loss associated with
      differences in pathologic features.

PMID- 9541521
TI  - Ultrastructural and electron diffraction of the bone-ceramic interfacial zone in
      coral and biphasic CaP implants.
AB  - We investigated the influence of natural coral implants used as a bone substitute
      on the quality of bone ingrowth in rabbits 2, 3, and 6 weeks after implantation.
      Explants were characterized by transmission electron microscopy and electron
      diffraction. Bone ingrowth has been previously demonstrated by light microscopy,
      however, few have been performed in electron microscopy to compare mineralized
      tissue ingrowth in coral implants which occurs at the expense of calcium
      carbonate to that of calcium phosphate (CaP) implants. The interface between
      coral aragonite and mineralized tissue or bone was abrupt, with no invasion of
      the aragonite structure by newly formed crystals, as occurs in micropores when
      biphasic CaP (BCP) ceramics were used. The restoring process appears to be
      different from that induced by BCP implants. Precipitation of needle-like apatite
      crystals on the CaCO3 implant surface was not observed. Instead, apatitic smooth
      shaped crystals formed in aggregates. The coral dissolution process does not
      release phosphate and so precipitation of apatite does not occur in the
      micropores of the coral implant, thereby limiting the formation of an apatite
      layer and hence bone bonding to the outer surface of the implant. In addition, on
      the outer surface of the implant, close to bone and a phosphorus source, the CaP
      crystals that do form are in aggregates presumably due to the carbonate and
      mismatch between the aragonite and the apatite. This seems to result in a delayed
      bone attachment or weaker bone bonding than CaP implants which encourage an
      epitaxial biological crystal deposition.

PMID- 9541522
TI  - EPR properties of synthetic apatites, deorganified dentine, and enamel.
AB  - Electron paramagnetic resonance spectroscopy (EPR) was used to study synthetic
      hydroxyapatite and approximately 1, 2, and 6% synthetic carbonated apatites,
      deorganified dentine, and enamel. The carbonated apatites were synthesized by
      hydrolysis of dicalcium phosphate. Comparisons were made with spectra from enamel
      and deorganified dentine. Microwave power saturation and dose responses were
      determined for the synthetic materials. The Marquardt version of the Levenberg
      decomposition method was used to extract individual signals from the apatite
      data. Two samples of dentine were irradiated with 25 and 100 Gy, respectively,
      from a 60Co source. The first sample was then deorganified at 200 degreesC using
      the Soxhlet extraction technique. A third sample was irradiated with 100 Gy after
      deorganification. The resulting EPR spectra were then compared. It was determined
      that the dosimetric signal of 2% synthetic carbonated apatite was approximately
      the same as that of enamel. It was also verified that the dosimetric signal
      saturates at about 2% in synthetic carbonated apatites. The study established
      that the precenters responsible for the dosimetric signal (g perpendicular =
      2.0018, g parallel = 1.9985) are preferentially concentrated in the surface
      accessible region of the mineral component, as shown by the approximately 80%
      attenuation of the dosimetric signal in dentine following deorganification. The
      precenters responsible are not destroyed by the deorganification since the
      magnitude of the dosimetric signal from the dentine specimen irradiated following
      deorganification was approximately twice that of the comparable untreated,
      irradiated sample. Finally, the dose response of 2 and 6% synthetic carbonated
      apatites was determined.

PMID- 9541523
TI  - Diurnal variation in total and undercarboxylated osteocalcin: influence of
      increased dietary phylloquinone.
AB  - A diurnal variation exists in blood levels of the vitamin K-dependent bone
      protein osteocalcin. However, it is not known whether the carboxylated and
      undercarboxylated constituents of osteocalcin also vary. Therefore, osteocalcin
      and undercarboxylated osteocalcin were measured in specimens collected every 4
      hours over a 24-hour period in nine healthy subjects (five males, four females)
      ages 20-33 years who were consuming a mixed diet containing 100 microg of
      phylloquinone. Osteocalcin and undercarboxylated osteocalcin were measured by
      radioimmunoassay (RIA) before and after treatment with barium sulfate. Although
      the percent undercarboxylated osteocalcin did not change, a diurnal variation was
      observed in total osteocalcin, carboxylated osteocalcin, and undercarboxylated
      osteocalcin, with peak concentrations at 4 a.m. and the lowest concentrations
      between 12 p.m. and 4 p.m. The difference between the total osteocalcin peak and
      trough concentrations averaged 28 +/- 7 (SEM)%. There were no gender differences
      in these rhythms. The effect of dietary phylloquinone as a modulator of these
      rhythms was evaluated in a randomized study by increasing phylloquinone intake to
      420 microg/day with fortified corn oil, split between the lunch and dinner meals.
      Total and carboxylated osteocalcin fluctuations and concentrations were not
      affected by the dietary treatment. The diurnal variation in undercarboxylated
      osteocalcin was abolished with supplementation and concentrations at 8 a.m. (14
      hours following supplementation) (2.3 +/- 0.2 ng/ml) were significantly lower
      than the unsupplemented levels (2.7 +/- 0.2 ng/mL, P = 0.006). The percentage of
      undercarboxylated osteocalcin was similarly decreased after supplementation (19.7
      +/- 1.3%) in relation to the mixed diet cycle (24.2 +/- 1.6%, P = 0.006) at 8
      a.m. on the second day. Dietary supplementation induced a fluctuation in
      percentage undercarboxylated osteocalcin with a decline in levels starting at
      approximately 12 a.m. Therefore, additional dietary phylloquinone does not appear
      to modulate the total osteocalcin diurnal rhythm, but can influence its
      undercarboxylated component.

PMID- 9541524
TI  - Effect of polyethylene on osteocalcin, alkaline phosphatase and procollagen
      secretion by human osteoblastic cells.
AB  - We have studied the direct effects of polyethylene particles on osteoblastic
      function in primary human bone cell cultures. The cells were obtained from
      trabecular bone fragments of patients undergoing knee reconstructive surgery.
      When the cells reached confluency, they were subcultured into two flasks, one
      untreated (control culture) and the other treated with polyethylene particles,
      and incubated until confluency. Osteoblastic function was evaluated by assaying
      osteocalcin, alkaline phosphatase, and C-terminal procollagen type I, with and
      without 1,25(OH)2D stimulation, in the cell-conditioned medium. We found that
      addition of polyethylene to these osteoblastic cell cultures induced higher
      levels of secreted osteocalcin after 1, 25(OH)2D stimulation. Alkaline
      phosphatase levels increased whereas C-terminal procollagen type I levels
      decreased in the cell conditioned medium after polyethylene was added to the
      cultures. Treatment of the control cultures with 1,25(OH)2D stimulated alkaline
      phosphatase levels and decreased C-terminal procollagen type I. However, these
      osteoblastic markers in 1,25(OH)2D-treated cells did not change in cultures with
      polyethylene. This study demonstrates that polyethylene particles have a direct
      effect on osteoblastic markers in human bone cells in culture.

PMID- 9541525
TI  - The PTH-calcium relationship during a range of infused PTH doses in the
      parathyroidectomized rat.
AB  - To establish the PTH dosage that maintains normal mineral homeostasis in the PTX
      rat, a series of doses of rat 1-34 PTH were infused via a subcutaneously
      implanted miniosmotic pump. The doses were 0, 0.011, 0.022, 0.044, and 0.11
      microg/100 g/hour. After 48 hours, serum calcium ranged from 5.56 +/- 0.02 to
      16.29 +/- 0.25 mg/dl, ANOVA P < 0.001, and serum phosphorus from 12.49 +/- 0.03
      to 5.33 +/- 0.34 mg/dl, ANOVA P < 0.001. By post hoc test, the serum calcium
      level was different (P < 0.05) at every PTH dose; the serum phosphorus level was
      different (P < 0.05) at every PTH dose except between the two highest doses. The
      PTH dosage that produced a normal serum calcium (10.09 +/- 0.10 mg/dl) and
      phosphorus (6.90 +/- 0.18 mg/dl) was 0.022 microg/100 g/hour. The relationship
      between increasing doses of PTH and both serum calcium and phosphorus was
      curvilinear and the calcium-phosphorus product was remarkably constant from a
      serum calcium of 7-13 mg/dl. The increase in serum calcium and the decrease in
      serum phosphorus were more rapid at lower than at higher PTH doses so that for
      both, an asymptote was reached. At the highest serum calcium values, the calcium
      phosphorus product increased and in individual rats, an increase in serum
      phosphorus was associated with a decrease in serum calcium. In summary, this
      study shows that (1) for rat 1-34 PTH, the normal replacement dose in the PTX rat
      with normal renal function on a normal diet is 0.022 microg/100 g/hour; (2) the
      relationship between PTH and both serum calcium and phosphorus is curvilinear,
      and an asymptote is reached for both; and (3) the calcium-phosphorus product is
      remarkably constant as the serum calcium increases from 7 to 13 mg/dl and only
      increased during marked hypercalcemia when serum phosphorus did not decrease
      further or even tended to increase.

PMID- 9541526
TI  - Plantar flexion force is related to calcaneus bone ultrasonic parameters in
      postmenopausal women.
AB  - The aim of this report was to study the relationship between the plantar flexion
      strength produced by contraction of the triceps surae (gastrocnemii-soleus)
      muscle and the calcaneus bone parameters assessed by quantitative ultrasound in
      45 healthy postmenopausal women. Plantar flexion strength was related to
      calcaneus broadband ultrasound attenuation (BUA) (r = 0.43, P = 0.003) and to
      speed of sound (SOS) (r = 0.3, P = 0.04). Plantar flexion appeared to predict
      ultrasonic properties, independently of body weight (R2 = 19% and 9% for BUA and
      SOS, respectively). These results suggest that the stresses related to locomotion
      locally enhance bone remodeling but further studies are needed to identify the
      respective role of the compressive strains related to ground reaction forces at
      heel-strike and the muscular tensile strains applied on the calcaneus where the
      calcaneal tendon is inserted.

PMID- 9541527
TI  - Bone mineral density and bone size in men with primary osteoporosis and vertebral
      fractures.
AB  - The bone mineral density (BMD) at the lumbar spine, proximal femur, and total
      skeleton was evaluated in 38 men with primary osteoporosis and vertebral
      fractures. BMD of the patients was significantly reduced over all skeletal areas
      compared with controls. The Z-score of the lumbar spine (-2.8 +/- 0.9) was less
      than that of the other areas (P < 0.001) except the legs (-2.5 +/- 1.1) (p.n.s.)
      showing that bone loss had a tendency to be greater over the axial skeleton.
      Vertebral dimensions compared with age-matched controls were as follows:
      projected L2-L4 area (cm 2): 45.7 +/- 5.6 versus 53.7 +/- 3. 6 (P < 0.001);
      vertebral width (cm): 4.37 +/- 0.44 versus 4.90 +/- 0. 36 (P < 0.001). Serum
      biochemical parameters and testosterone levels were similar between osteoporotic
      and control men. We conclude that men with vertebral osteoporotic fractures have
      reduced vertebral BMD and vertebral dimensions compared with age-matched
      controls. Thus, these findings indicate that the achievement of a reduced bone
      size at the end of the growth period or a failure of periosteal increase during
      adult life is likely to contribute to the pathogenesis of the vertebral fractures
      observed in older men.

PMID- 9541528
TI  - Metacarpal radiogrammetry by computed radiography in postmenopausal women with
      Colles' fracture and vertebral crush fracture syndrome.
AB  - Based on the hypothesis that the underlying osteoporotic mechanism of Colles'
      fracture in postmenopausal women is similar to that of other osteoporotic
      fractures, that is, cortical bone resorption as opposed to cancellous bone
      resorption, the rate of corticoendosteal bone loss was compared in 40 normal
      postmenopausal women [average age 68.4 +/- 7.1 years; 20 +/- 4 years since
      menopause (YSM)], in 35 postmenopausal women with Colles' fracture (age 69.4 +/-
      7.5 years, 22 +/- 8 YSM), in 35 normal postmenopausal women with vertebral crush
      fracture (age 69.4 +/- 7.5 years, 22 +/- 8 YSM, and in 35 normal premenopausal
      women (age 36.1 +/- 7.9 years). Radiogrammetry by digital radiography of the
      second metacarpal was used to measure external (ED) and internal (ID) diameter,
      cortical thickness (CCT), cortical area (CA), and the ratio of cortical area to
      total area (CA/TA). The ID values of the groups of postmenopausal women were
      subtracted from the ID value of the premenopausal women and the result was
      divided by YSM to obtain the rate of corticoendosteal resorption/year (DeltaC),
      CA resorption year (DeltaCA) and CA/TA resorption/year (DeltaCA/TA). ID, DeltaC,
      DeltaCA, and DeltaCA/TA all were larger in the postmenopausal women with Colles'
      and vertebral crush fractures than in the normal postmenopausal women (ANOVA: all
      P < 0.0001). ID, CCT, DeltaC, CA, DeltaCA, and DeltaCA/TA did not differ between
      the two groups of postmenopausal women with fractures. DeltaC was 87% greater in
      postmenopausal women with vertebral crush fracture and 116% greater in women with
      Colles' fracture than in normal postmenopausal women. These results indicate that
      the loss of cortical bone is an important factor in Colles' fracture in
      postmenopausal women.

PMID- 9541529
TI  - A Cold Look at Odd Vertebrate Phylogenies

PMID- 9541530
TI  - Is there sufficient evidence to elevate the orangutan of Borneo and Sumatra to
      separate species?

PMID- 9541531
TI  - Response

PMID- 9541532
TI  - The mitochondrial DNA molecule of the hagfish (Myxine glutinosa) and vertebrate
      phylogeny.
AB  - The vertebrates are traditionally classified into two distinct groups, Agnatha
      (jawless vertebrates) and Gnathostomata (jawed vertebrates). Extant agnathans are
      represented by hagfishes (Myxiniformes) and lampreys (Petromyzontiformes),
      frequently grouped together within the Cyclostomata. Whereas the recognition of
      the Gnathostomata as a clade is commonly acknowledged, a consensus has not been
      reached regarding whether or not Cyclostomata represents a clade. In the present
      study we have used newly established sequences of the protein-coding genes of the
      mitochondrial DNA molecule of the hagfish to explore agnathan and gnathostome
      relationships. The phylogenetic analysis of Pisces, using echinoderms as
      outgroup, placed the hagfish as a sister group of Vertebrata sensu stricto, i.e.,
      the lamprey and the gnathostomes. The phylogenetic analysis of the Gnathostomata
      identified a basal divergence between gnathostome fishes and a branch leading to
      birds and mammals, i.e., between "Anamnia" and Amniota. The lungfish has a basal
      position among gnathostome fishes with the teleosts as the most recently evolving
      lineage. The findings portray a hitherto unrecognized polarity in the evolution
      of bony fishes. The presently established relationships are incompatible with
      previous molecular studies.

PMID- 9541533
TI  - The immunoglobulin superfamily: an insight on its tissular, species, and
      functional diversity.
AB  - The immunoglobulin superfamily (IgSF) is a heterogenic group of proteins built on
      a common fold, called the Ig fold, which is a sandwich of two beta sheets.
      Although members of the IgSF share a similar Ig fold, they differ in their tissue
      distribution, amino acid composition, and biological role. In this paper we
      report an up-to-date compilation of the IgSF where all known members of the IgSF
      are classified on the basis of their common functional role (immune system,
      antibiotic proteins, enzymes, cytokine receptors, etc.) and their distribution in
      tissue (neural system, extracellular matrix, tumor marker, muscular proteins,
      etc.), or in species (vertebrates, invertebrates, bacteria, viruses, fungi, and
      plants). The members of the family can contain one or many Ig domains, comprising
      two basic types: the constant domain (C), with seven strands, and the variable
      domain (V), with eight, nine, or ten strands. The different overviews of the IgSF
      led to the definition of new domain subtypes, mainly concerning the C type, based
      on the distribution of strands within the two sheets. The wide occurrence of the
      Ig fold and the much less conserved sequences could have developed from a common
      ancestral gene and/or from a convergent evolutionary process. Cell adhesion and
      pattern recognition seem to be the common feature running through the entire
      family.

PMID- 9541534
TI  - A unique fungal lysine biosynthesis enzyme shares a common ancestor with
      tricarboxylic acid cycle and leucine biosynthetic enzymes found in diverse
      organisms.
AB  - Fungi have evolved a unique alpha-amino-adipate pathway for lysine biosynthesis.
      The fungal-specific enzyme homoaconitate hydratase from this pathway is
      moderately similar to the aconitase-family proteins from a diverse array of
      taxonomic groups, which have varying modes of obtaining lysine. We have used the
      similarity of homoaconitate hydratase to isopropylmalate isomerase (serving in
      leucine biosynthesis), aconitase (from the tricarboxylic acid cycle), and iron
      responsive element binding proteins (cytosolic aconitase) from fungi and other
      eukaryotes, eubacteria, and archaea to evaluate possible evolutionary scenarios
      for the origin of this pathway. Refined sequence alignments show that aconitase
      active site residues are highly conserved in each of the enzymes, and intervening
      sequence sites are quite dissimilar. This pattern suggests strong purifying
      selection has acted to preserve the aconitase active site residues for a common
      catalytic mechanism; numerous other substitutions occur due to adaptive evolution
      or simply lack of functional constraint. We hypothesize that the similarities are
      the remnants of an ancestral gene duplication, which may not have occurred within
      the fungal lineage. Maximum likelihood, neighbor joining, and maximum parsimony
      phylogenetic comparisons show that the alpha-aminoadipate pathway enzyme is an
      outgroup to all aconitase family proteins for which sequence is currently
      available.

PMID- 9541535
TI  - Synonymous and nonsynonymous rate variation in nuclear genes of mammals.
AB  - A maximum likelihood approach was used to estimate the synonymous and
      nonsynonymous substitution rates in 48 nuclear genes from primates, artiodactyls,
      and rodents. A codon-substitution model was assumed, which accounts for the
      genetic code structure, transition/transversion bias, and base frequency biases
      at codon positions. Likelihood ratio tests were applied to test the constancy of
      nonsynonymous to synonymous rate ratios among branches (evolutionary lineages).
      It is found that at 22 of the 48 nuclear loci examined, the
      nonsynonymous/synonymous rate ratio varies significantly across branches of the
      tree. The result provides strong evidence against a strictly neutral model of
      molecular evolution. Our likelihood estimates of synonymous and nonsynonymous
      rates differ considerably from previous results obtained from approximate
      pairwise sequence comparisons. The differences between the methods are explored
      by detailed analyses of data from several genes. Transition/transversion rate
      bias and codon frequency biases are found to have significant effects on the
      estimation of synonymous and nonsynonymous rates, and approximate methods do not
      adequately account for those factors. The likelihood approach is preferable, even
      for pairwise sequence comparison, because more realistic models about the
      mutation and substitution processes can be incorporated in the analysis.

PMID- 9541537
TI  - Evidence for horizontal transfer from Streptococcus to Escherichia coli of the
      kfiD gene encoding the K5-specific UDP-glucose dehydrogenase.
AB  - Capsular polysaccharides are important virulence factors both in Gram-positive
      and Gram-negative bacteria. A similar cluster organization of the genes involved
      in the synthesis of bacterial exopolysaccharides has been postulated in both
      cases, suggesting that these clusters evolved by module assembly. Horizontal gene
      transfer has been postulated to explain the polymorphism found in these cellular
      polymers. The cap1 K and cap3A genes coding for the pneumococcal type 1 and type
      3 UDP-glucose dehydrogenases, respectively, have been compared with other UDP
      sugar dehydrogenases. We have observed that the evolutionary distance between
      Cap1K and Cap3A is approximately equal to that found between Cap1K (or Cap3A) and
      other UDP-GlcDH of families evolutionarily distant like KfiD, the dehydrogenase
      from Escherichia coli K5. On the basis of comparisons of G + C content, patterns
      of synonymous and nonsynonymous substitutions, dinucleotide frequencies, and
      codon usage bias, we conclude that the kfiD gene has been introduced into E. coli
      from an exogenous source, probably from a streptococcal species.

PMID- 9541536
TI  - Mitochondrial DNA of the coral Sarcophyton glaucum contains a gene for a
      homologue of bacterial MutS: a possible case of gene transfer from the nucleus to
      the mitochondrion.
AB  - The nucleotide sequences of two segments of 6,737 ntp and 258 nto of the 18.4-kb
      circular mitochondrial (mt) DNA molecule of the soft coral Sarcophyton glaucum
      (phylum Cnidaria, class Anthozoa, subclass Octocorallia, order Alcyonacea) have
      been determined. The larger segment contains the 3' 191 ntp of the gene for
      subunit 1 of the respiratory chain NADH dehydrogenase (ND1), complete genes for
      cytochrome b (Cyt b), ND6, ND3, ND4L, and a bacterial MutS homologue (MSH), and
      the 5' terminal 1,124 ntp of the gene for the large subunit rRNA (1-rRNA). These
      genes are arranged in the order given and all are transcribed from the same
      strand of the molecule. The smaller segment contains the 3' terminal 134 ntp of
      the ND4 gene and a complete tRNA(f-Met) gene, and these genes are transcribed in
      opposite directions. As in the hexacorallian anthozoan, Metridium senile, the mt
      genetic code of S. glaucum is near standard: that is, in contrast to the
      situation in mt-genetic codes of other invertebrate phyla, AGA and AGG specify
      arginine, and ATA specifies isoleucine. However, as appears to be universal for
      metazoan mt-genetic codes, TGA specifies tryptophan rather than termination.
      Also, as in M. senile the mt-tRNA(f-Met) gene has primary and secondary
      structural features resembling those of Escherichia coli initiator tRNA,
      including standard dihydrouridine and T psi C loop sequences, and a mismatched
      nucleotide pair at the top of the amino-acyl stem. The presence of a mutS gene
      homologue, which has not been reported to occur in any other known mtDNA,
      suggests that there is mismatch repair activity in S. glaucum mitochondria. In
      support of this, phylogenetic analysis of MutS family protein sequences indicates
      that the S. glaucum mtMSH protein is more closely related to the nuclear DNA
      encoded mitochondrial mismatch repair protein (MSH1) of the yeast Saccharomyces
      cerevisiae than to eukaryotic homologues involved in nuclear function, or to
      bacterial homologues. Regarding the possible origin of the S. glaucum mtMSH gene,
      the phylogenetic analysis results, together with comparative base composition
      considerations, and the absence of an MSH gene in any other known mtDNA best
      support the hypothesis that S. glaucum mtDNA acquired the mtMSH gene from nuclear
      DNA early in the evolution of octocorals. The presence of mismatch repair
      activity in S. glaucum mitochondria might be expected to influence the rate of
      evolution of this organism's mtDNA.

PMID- 9541538
TI  - Potentially active copies of the gypsy retroelement are confined to the Y
      chromosome of some strains of Drosophila melanogaster possibly as the result of
      the female-specific effect of the flamenco gene.
AB  - Gypsy is an endogenous retrovirus present in the genome of Drosophila
      melanogaster. This element is mobilized only in the progeny of females which
      contain active gypsy elements and which are homozygous for permissive alleles of
      a host gene called flamenco (flam). Some data strongly suggest that gypsy
      elements bearing a diagnostic HindIII site in the central region of the
      retrovirus body represent a subfamily that appears to be much more active than
      elements devoid of this site. We have taken advantage of this structural
      difference to assess by the Southern blotting technique the genomic distribution
      of active gypsy elements. In some of the laboratory Drosophila stocks tested,
      active gypsy elements were found to be restricted to the Y chromosome. Further
      analyses of 14 strains tested for the permissive vs. restrictive status of their
      flamenco alleles suggest that the presence of permissive alleles of flam in a
      stock tends to be associated with the confinement of active gypsy elements to the
      Y chromosome. This might be the result of the female-specific effect of flamenco
      on gypsy activity.

PMID- 9541539
TI  - Multiple origins of fungal group I introns located in the same position of
      nuclear SSU rRNA gene.
AB  - The archiascomycetous fungus Protomyces pachydermus has two group I introns
      within the nuclear small subunit (nSSU) rRNA gene. One of these introns has an
      internal open reading frame (ORF) that encodes a predicted protein of 228 amino
      acid residues. On the other hand, Protomyces macrosporus has two group I introns
      that insert at the same positions as P. pachydermus, which have no ORF. Each
      alignment was constructed with Protomyces group I introns located in the same
      position and other introns retrieved by the BLAST Search. Each phylogenetic tree
      based on the alignment shows that Protomyces introns are monophyletic but the
      relationships among fungal introns do not reflect on the fungal phylogeny.
      Therefore, it is suggested that two different horizontal transfers of group I
      introns occurred at the early stage of Protomyces species diversification.

PMID- 9541540
TI  - Selection on the codon bias of chloroplast and cyanelle genes in different plant
      and algal lineages.
AB  - In the plant chloroplast genome the codon usage of the highly expressed psbA gene
      is unique and is adapted to the tRNA population, probably due to selection for
      translation efficiency. In this study the role of selection on codon usage in
      each of the fully sequenced chloroplast genomes, in addition to Chlamydomonas
      reinhardtii, is investigated by measuring adaptation to this pattern of codon
      usage. A method is developed which tests selection on each gene individually by
      constructing sequences with the same amino acid composition as the gene and
      randomly assigning codons based on the nucleotide composition of noncoding
      regions of that genome. The codon bias of the actual gene is then compared to a
      distribution of random sequences. The data indicate that within the algae
      selection is strong in Cyanophora paradoxa, affecting a majority of genes, of
      intermediate intensity in Odontella sinensis, and weaker in Porphyra purpurea and
      Euglena gracilis. In the plants, selection is found to be quite weak in Pinus
      thunbergii and the angiosperms but there is evidence that an intermediate level
      of selection exists in the liverwort Marchantia polymorpha. The role of selection
      is then further investigated in two comparative studies. It is shown that average
      relative codon bias is correlated with expression level and that, despite
      saturation levels of substitution, there is a strong correlation among the algae
      genomes in the degree of codon bias of homologous genes. All of these data
      indicate that selection for translation efficiency plays a significant role in
      determining the codon bias of chloroplast genes but that it acts with different
      intensities in different lineages. In general it is stronger in the algae than
      the higher plants, but within the algae Euglena is found to have several unusual
      features which are noted. The factors that might be responsible for this
      variation in intensity among the various genomes are discussed.

PMID- 9541541
TI  - The rate of mitochondrial 12S rRNA gene evolution is similar in freshwater
      turtles and marsupials.
AB  - Assertions that the "conventional" rate of mitochondrial DNA (mtDNA) evolution is
      reduced in poikilotherms in general and turtles in particular were tested for
      side-necked turtles (Pleurodira: Chelidae). Homologous data sets of mitochondrial
      12S rRNA gene sequences were used to compare the average divergence between the
      Australian and South American species for two Gondwanan groups: the chelid
      turtles and the marsupials. The mean nucleotide divergences between continental
      groups for both the turtles and the marsupials are remarkably similar. These data
      suggest that the rate of evolution of mitochondrial 12S rRNA gene is not
      substantially slower in turtles than in the homeothermic marsupials.

PMID- 9541542
TI  - Characterizing sequence variation in the VP1 capsid proteins of foot and mouth
      disease virus (serotype 0) with respect to virion structure.
AB  - The VP1 capsid protein of foot and mouth disease virus (FMDV) is highly
      polymorphic and contains several of the major immunogenic sites important to
      effective antibody neutralization and subsequent viral clearance by the immune
      system. Whether this high level of polymorphism is of adaptive value to the virus
      remains unknown. In this study we examined sequence data from a set of 55
      isolates in order to establish the nature of selective pressures acting on this
      gene. Using the known molecular structure of VP1, the rates and ratios of
      different types of nonsynonymous and synonymous changes were compared between
      different parts of the protein. All parts of the protein are subject to purifying
      selection, but this is greatest amongst those amino acid residues within beta
      strands and is significantly reduced at residues exposed on the capsid surface,
      which include those residues demonstrated by previous mutational analyses to
      permit the virus to escape from monoclonal antibody binding. The ratios of
      nonsynonymous substitution resulting in various forms of physicochemically
      radical and conserved amino acid change were shown to be largely equal throughout
      these different parts of the protein. There was a consistently higher level of
      nonsynonymous and charge radical sites in those regions of the gene coding for
      residues exposed on the outer surface of the capsid and a marked difference in
      the use of amino acids between surface and nonsurface regions of the protein.
      However, the analysis is consistent with the hypothesis that the observed
      sequence variation arises where it is least likely to be disruptive to the higher
      order structure of the protein and is not necessarily due to positive Darwinian
      selection.

PMID- 9541543
TI  - Ligand-binding domains in vitellogenin receptors and other LDL-receptor family
      members share a common ancestral ordering of cysteine-rich repeats.
AB  - Insect vitellogenin and yolk protein receptors (VgR/YPR) are newly discovered
      members of the low-density lipoprotein receptor (LDLR) family, which is
      characterized by a highly conserved arrangement of repetitive modular elements
      homologous to functionally unrelated proteins. The insect VgR/YPRs are unique in
      having two clusters of complement-type cysteine-rich (class A) repeats or
      modules, with five modules in the first cluster and seven in the second cluster,
      unlike classical LDLRs which have a single seven-module cluster, vertebrate VgRs
      and very low density lipoprotein receptors (VLDLR) which have a single eight
      module cluster, and LDLR-related proteins (LRPs) and megalins which have four
      clusters of 2-7, 8, 10, and 11 modules. Alignment of clusters across subfamilies
      by conventional alignment programs is problematic because of the repetitive
      nature of the component modules which may have undergone rearrangements,
      duplications, and deletions during evolution. To circumvent this problem, we
      "fingerprinted" each class A module in the different clusters by identifying
      those amino acids that are both relatively conserved and relatively unique within
      the cluster. Intercluster reciprocal comparisons of fingerprints and aligned
      sequences allowed us to distinguish four cohorts of modules reflecting shared
      recent ancestry. All but two of the 57 modules examined could be assigned to one
      of these four cohorts designated A, B, C, and D. Alignment of clusters based on
      modular cohorts revealed that all clusters are derived from a single primordial
      cluster of at least seven modules with a consensus arrangement of CDCADBC. All
      extant clusters examined are consistent with this consensus, though none matches
      it perfectly. This analysis also revealed that the eight-module clusters in
      vertebrate VgRs, insect VgR/YPRs, and LRP/megalins are not directly homologous
      with one another. Assignment of modules to cohorts permitted us to properly align
      32 class A clusters from all four LDLR subfamilies for phylogenetic analysis. The
      results revealed that smaller one-cluster and two-cluster members of the family
      did not originate from the breakup of a large two-cluster or four-cluster
      receptor. Similarly, the LRP/megalins did not arise from the duplication of a two
      cluster insect VgR/YPR-like progenitor. Rather, it appears that the multicluster
      receptors were independently constructed from the same single-cluster ancestor.

PMID- 9541544
TI  - Modeling based on the structure of vicilins predicts a histidine cluster in the
      active site of oxalate oxidase.
AB  - It is known that germin, which is a marker of the onset of growth in germinating
      wheat, is an oxalate oxidase, and also that germins possess sequence similarity
      with legumin and vicilin seed storage proteins. These two pieces of information
      have been combined in order to generate a 3D model of germin based on the
      structure of vicilin and to examine the model with regard to a potential oxalate
      oxidase active site. A cluster of three histidine residues has been located
      within the conserved beta-barrel structure. While there is a relatively low level
      of overall sequence similarity between the model and the vicilin structures, the
      conservation of amino acids important in maintaining the scaffold of the beta
      barrel lends confidence to the juxtaposition of the histidine residues. The
      cluster is similar structurally to those found in copper amine oxidase and other
      proteins, leading to the suggestion that it defines a metal-binding location
      within the oxalate oxidase active site. It is also proposed that the structural
      elements involved in intermolecular interactions in vicilins may play a role in
      oligomer formation in germin/oxalate oxidase.

PMID- 9541545
TI  - Frequent gene conversion between human red and green opsin genes.
AB  - To study the evolution of human X-linked red and green opsin genes, genomic
      sequences in large regions of the two genes were compared. The divergences in
      introns 3, 4, and 5 and the 3' flanking sequence of the two genes are
      significantly lower than those in exons 4 and 5. The homogenization mechanism of
      introns and the 3' flanking sequence of human red and green opsin genes is
      probably gene conversion, which also occurred in exons 1 and 6. At least one gene
      conversion event occurred in each of three regions (1, 3, and 5) in the sequences
      compared. In conclusion, gene conversion has occurred frequently between human
      red and green opsin genes, but exons 2, 3, 4, and 5 have been maintained distinct
      between the two genes by natural selection.

PMID- 9541547
TI  - The Use of Carbon Substrate Utilization Patterns in Environmental and Ecological
      Microbiology

PMID- 9541546
TI  - Comparative Evolutionary Rates of Introns and Exons in Murine Rodents

PMID- 9541548
TI  - Predicting Epipelic Diatom Exopolymer Concentrations in Intertidal Sediments from
      Sediment Chlorophyll a

PMID- 9541549
TI  - Variation of Microcystin Content of Cyanobacterial Blooms and Isolated Strains in
      Lake Grand-Lieu (France)

PMID- 9541550
TI  - Bacterial Colonization and Ectoenzymatic Activity in Phytoplankton-Derived Model
      Particles: Cleavage of Peptides and Uptake of Amino Acids

PMID- 9541551
TI  - Acclimation of Cyanobacterial Communities in Rice Fields and Response of
      Nitrogenase Activity to Light Regime

PMID- 9541552
TI  - Microbial Communities in High and Low Recharge Environments: Implications for
      Microbial Transport in the Vadose Zone

PMID- 9541553
TI  - Potential Physiological Activities of Fungi and Bacteria in Relation to Plant
      Litter Decomposition along a Gap Size Gradient in a Natural Subtropical Forest

PMID- 9541554
TI  - Validation of a Three-Stage Compound Continuous Culture System for Investigating
      the Effect of Retention Time on the Ecology and Metabolism of Bacteria in the
      Human Colon

PMID- 9541555
TI  - Experimental Vibriosis Induction with Vibrio alginolyticus of Larvae of the
      Catarina Scallop (Argopecten ventricosus =circularis) (Sowerby II, 1842)

PMID- 9541556
TI  - Increase of Copper Toxicity to Growth of Chlorella vulgaris with Increase of
      Light Intensity

PMID- 9541557
TI  - The Effect of the Herbicide Mecoprop on Heliscus lugdunensis and Its Influence on
      the Preferential Feeding of Gammarus Pseudolimnaeus.

PMID- 9541558
TI  - Taxonomic Lactobacillus Composition of Feces from Human Newborns during the First
      Few Days

PMID- 9541559
TI  - Unusual gene arrangement of the bidirectional hydrogenase and functional analysis
      of its diaphorase subunit HoxU in respiration of the unicellular cyanobacterium
      anacystis nidulans 
AB  - The bidirectional, NAD+-dependent hydrogenase from cyanobacteria is encoded by
      the structural genes hoxFUYH, which have been found to be clustered, though
      interspersed with different open reading frames (ORFs), in the heterocystous, N2
      fixing Anabaena variabilis and in the unicellular Synechocystis PCC 6803. In
      another unicellular, non N2-fixing cyanobacterium, Anacystis nidulans, hoxF has
      now been identified as being separated by at least 16 kb from the residual
      structural genes hoxUYH. An ORF (termed hoxE gene) is located immediately
      upstream of hoxF in A. nidulans and in Synechocystis. Its deduced amino acid
      sequence shows similarities to the NuoE subunit of NADH dehydrogenase I of E.
      coli, to the homologous subunit of respiratory complex I in mitochondria, and
      also to the first 104 amino acids of HoxF in A. nidulans and Synechocystis. The
      diversity in the arrangement of hydrogenase genes in cyanobacteria is puzzling.
      The subunits HoxE, HoxF, and HoxU of the diaphorase part of the bidirectional
      hydrogenase have been discussed to be shared both by respiratory complex I and
      bidirectional hydrogenase in cyanobacteria. Different hoxU mutants were obtained
      by inserting a lacZKmR cassette into the gene both in A. nidulans and Anacystis
      PCC 7942. Such mutants showed reduced H2-evolution activities catalyzed by the
      bidirectional hydrogenase, but had nonimpaired respiratory O2-uptake. A common
      link between respiratory complex I and the diaphorase part of the bidirectional
      hydrogenase in cyanobacteria may still exist, but this hypothesis could not be
      verified in the present study by analyzing defined mutants impaired in one of the
      diaphorase genes.

PMID- 9541560
TI  - Transcriptional regulation of the Prevotella ruminicola recA gene.
AB  - The regulation of the recA gene expression in the obligately anaerobic rumen
      bacterium Prevotella ruminicola was investigated by monitoring the recA-specific
      transcript level. P. ruminicola recA forms a monocistronic unit, but no SOS-box
      sequences resembling those of Escherichia coli or Bacillus subtilis can be
      identified upstream of the recA coding region. At the same time, we observed a
      fivefold increase in the level of recA mRNA in response to DNA damaging agents,
      mitomycin C and methyl methanesulfonate, as well as under conditions of oxidative
      stress. No induction was detected when growth of P. ruminicola was arrested by
      shifting to acidic (pH 4.8) conditions. Primer extension experiment revealed the
      three very close transcriptional start sites for recA. The putative -10 and -35
      RNA polymerase binding regions were proposed on the basis of transcript mapping.
      These regions bear very little similarity to the E. coli (sigma70) and B.
      subtilis (sigmaA) consensus sequences, as well as to the recognition sites of
      other minor sigma-factors. Transcript mapping experiments in E. coli expressing
      P. ruminicola recA confirmed that the transcription machineries of these two
      bacteria recognize completely different regulatory sequences on the template to
      initiate transcription. Preliminary DNase I footprinting analysis data revealed
      that the region of imperfect dyad symmetry (AATTATAATCAATTATAAAT) found between
      the putative -10 region and the translation initiation codon may serve as an SOS
      box-like regulatory sequence in P. ruminicola. This sequence bears no similarity
      to the known SOS-box sequences and, in particular, to that of E. coli and other
      Gram-negative bacteria.

PMID- 9541561
TI  - Flow cytometry demonstrates bacteriocin-induced injury to Listeria monocytogenes.
AB  - Flow cytometry was used to study the effect of the bacteriocin leucocin B-TA11a
      on Listeria (L.) monocytogenes. Mixed proportions of dead and live control
      populations were analyzed by flow cytometry to determine detection limits of the
      Dead/Live Baclight Bacterial Viability KitTM. High correlations for flow
      cytometric detection of defined proportions of live or dead cells in mixtures
      between 10 and 100% of dead (r2 = 0.97) or live (r2 = 0.99) cells were obtained.
      However, mixtures containing less than 10% of either live or dead control cells
      gave correlations below 0.72. The growth of L. monocytogenes in the absence and
      presence of leucocin B-TA11a was analyzed by flow cytometry with Baclight, plate
      counts, and optical density measurements. Although leucocin B-TA11a initially
      inhibited listerial growth, the uptake of both Baclight dyes suggested that cells
      remained viable but became leaky, possibly indicating bacteriocin-induced pore
      formation in the target membranes.

PMID- 9541562
TI  - Evidence of a Restriction/Modification system in lactobacillus delbrueckii subsp.
      lactis CNRZ 326 
AB  - Lactobacillus delbrueckii subsp. lactis (Lb. lactis) CNRZ 326 is widely used in
      the propagation of Lb. delbrueckii bacteriophages. In this study, evidence is
      presented that this strain possesses a restriction-modification (R/M) system. The
      mitomycin C-induced temperate bacteriophage lb539 has a reduced efficiency of
      plaquing (EOP) on CNRZ 326 cells (EOP = 10(-3)), but after several passages on
      this strain, or on the indicator strain Lb. lactis LKT, the recovered phages
      (phages lb539.326 and lb539.LKT) have an EOP equal to 1. Restrictive development
      on CNRZ 326 was also observed after phage lb539.326 was propagated on the strain
      Lb. lactis CRL 934. The R/M system was also active against the virulent Lb.
      delbrueckii phage ll-h. Plasmid DNA was not detected in CNRZ 326, which suggests
      that the R/M system described is chromosomally encoded.

PMID- 9541563
TI  - Relationship between serotype A encapsulation and a 40-kDa lipoprotein in
      Pasteurella multocida.
AB  - Eleven serotype A encapsulated and nonencapsulated strains of Pasteurella
      multocida were examined with regard to lipoprotein content. Relative amounts of
      an approximately 40-kDa lipoprotein (Plp-40) were found to correlate directly
      with the degree of encapsulation in that heavily encapsulated strains exhibited
      the greatest amounts, while nonencapsulated strains possessed little or no Plp
      40.

PMID- 9541564
TI  - Spore coat protein synergizes bacillus thuringiensis crystal toxicity for the
      indianmeal moth 
AB  - Spores from Bacillus thuringiensis serovars kurstaki and entomocidus synergized
      crystal protein toxicity for larvae of the Indianmeal moth (Plodia
      interpunctella). Preparations of spore-crystal mixtures of either serovar were
      more toxic for the larvae than either purified spores or crystals alone (based on
      dry weight). Spores lost 53% of their toxicity for the Indianmeal moth after 2 h
      of UV-irradiation, but remained partially toxic (28%) even after 4 h of
      irradiation. Spore coat protein was toxic for the Indianmeal moth and was
      synergistic with B. thuringiensis serovar kurstaki HD-1 crystal protein. Enhanced
      toxicity of the combined spore-crystal preparation was attributed to a
      combination of crystal and spore coat protein, and included the effects of spore
      germination and resulting septicemia in the larval hemolymph. Ultraviolet
      irradiation of spores reduced the toxicity from septicemia but not the synergism
      caused by spore coat protein. The potencies of spore-crystal preparations must be
      carefully evaluated on the basis of contributions from all three factors.

PMID- 9541565
TI  - Anaerobic degradation of glycerol by desulfovibrio fructosovorans and D.
      carbinolicus and evidence for glycerol-dependent utilization of 1,2-propanediol 
AB  - The degradation of glycerol by Desulfovibrio carbinolicus and Desulfovibrio
      fructosovorans was tested in pure culture with sulfate and in coculture with
      Methanospirillum hungatei. Desulfovibrio carbinolicus degraded glycerol into 3
      hydroxypropionate with the formation of sulfide in pure culture and methane in
      the coculture. The maximum growth rates were 0.063 h-1 in pure culture and 0.014
      h-1 in coculture (corresponding growth yields: 8.9 and 6.0 g dry weight/mol
      glycerol). With D. fructosovorans, the pathway of glycerol degradation depended
      upon the terminal electron acceptor. Acetate and sulfide were produced in the
      presence of sulfate, while 3-hydroxypropionate and methane were formed by the
      syntrophic association with M. hungatei. The maximum growth rates were 0.057 h-1
      in pure culture and 0.020 h-1 in coculture (corresponding growth yields: 8.9 and
      6.0 g dry weight/mol glycerol). In a medium containing both glycerol and 1,2
      propanediol but no sulfate, D. carbinolicus and D. fructosovorans degraded both
      substrates. A drop in the concentration of 1,3-propanediol was observed, and
      propionate and n-propanol production was recorded. Putative biochemical pathways
      of 1,2-propanediol degradation by D. carbinolicus and D. fructosovorans indicated
      that the enzymes involved in this metabolism are present only when the strains
      are grown on a mixture of 1,2-propanediol and glycerol without sulfate.

PMID- 9541566
TI  - The effect of longterm exposure to mercury on the bacterial community in marine
      sediment.
AB  - The aim of this study was to investigate the effect of mercury contamination on
      bacterial community structure and function. Bacterial communities from two sites,
      a mercury-contaminated site inside the harbor of Copenhagen, Denmark (CH) and a
      unpolluted control site, Koge Buge (KB), were compared with respect to diversity
      indices, of antibiotic- and heavy metal-resistance patterns, abundance and self
      transmissibility of plasmids in resistant isolates (endogenous isolation).
      Furthermore, the potential for gene transfer between indigenous bacteria was
      assessed by the exogenous plasmid isolation approach. It was found that
      resistance to all the tested compounds was higher in the mercury-polluted
      sediment than the control sediment. The abundance of plasmids was higher at the
      polluted site, where 62% of the isolates contained plasmids, whereas only 29% of
      the isolates from the control sediment contained plasmids. Furthermore, the
      frequencies of large plasmids and plasmids per isolates were found to be higher
      in the contaminated sediment. Exogenous plasmid isolations revealed high
      occurrence of Hg and tetracycline resistance, self-transmissible plasmids in CH
      sediment (1.8 x 10(-5) transconjugants per recipients) relative to KB sediment
      (3.0 x 10(-8) T/R). Shannon-Weaver diversity indices showed no difference in the
      diversity of the isolates from the two sites, and Hg-resistant isolates from CH
      were found to be as diverse as the CH isolates in total. This may be owing to
      high level of self-transmissible Hg resistance plasmids found in CH.

PMID- 9541567
TI  - Low-frequency electromagnetic fields alter the replication cycle of MS2
      bacteriophage.
AB  - The effect of exposure to 60-Hz electromagnetic fields (EMFs) on RNA coliphage
      MS2 replication was studied. EMF exposure commenced when the bacterial cultures
      were inoculated with the phage (t = 0). In 12 experiments in which the strength
      of the field was 5 G, a significant delay in phage yield was found in the EMF
      exposed cultures 45-65 min after inoculation, compared with control cultures.
      However, the EMF did not alter the final phage concentration. Experiments at 25 G
      (N = 5) suggested that the stronger field resulted in both impeded phage
      replication and increased phage yield. No differences between test groups were
      found in experiments involving sham-EMF exposure, thereby indicating that the
      results obtained with the EMFs were not due to systematic error. It appears that
      MS2, which codes for only four proteins, is the simplest biological system in
      which an EMF-induced effect has been demonstrated. The MS2 system is, therefore,
      conducive to follow-up studies aimed at understanding the level and nature of the
      underlying interaction process, and perhaps to biophysical modeling of the
      interaction process.

PMID- 9541568
TI  - Pulsed-field gel electrophoresis analysis of the genome of Rhodococcus fascians:
      genome size and linear and circular replicon composition in virulent and
      avirulent strains.
AB  - Total DNA of virulent and avirulent strains of Rhodococcus fascians was resolved
      by pulsed-field gel electrophoresis (PFGE) into a discrete number of fragments by
      digestion with the endonucleases AseI and DraI. Restriction endonucleases PacI,
      PmeI, and SwaI yielded no fragments upon digestion of R. fascians genome, and all
      the other tested endonucleases recognizing 6 bp released too many fragments. The
      genome size was 5.6 megabases for the type strain R. fascians DSM 20669, and 5.8
      megabases for the virulent R. fascians D188 strain. However the genome size of R.
      fascians CECT 3001 (NRRL B15096) was 8.0 megabases. No linear chromosome in the
      megabase range was observed under pulse conditions in which Saccharomyces
      cerevisiae and Schizosaccharomyces pombe chromosomes were perfectly resolved,
      suggesting that the R. fascians chromosome is circular. A new linear plasmid
      pIRN640 of 640 kb was found in the avirulent R. fascians CECT 3001 that did not
      hybridize with a probe internal to the fas region of pFiD188 known to be involved
      in plant pathogenicity in the virulent strain R. fascians D188. Virulence was
      correlated in all strains tested with the presence of the fas region. The AseI
      and DraI bands corresponding to the extrachromosomal elements were identified
      providing the basis for a physical map of this organism.

PMID- 9541569
TI  - Identification and characterization of nucleotide sequence differences in three
      virulence-associated genes of listeria monocytogenes strains representing
      clinically important serotypes.
AB  - Listeria monocytogenes is a Gram-positive, facultative intracellular bacterium
      that causes invasive, often fatal, disease in susceptible hosts. As a foodborne
      pathogen, the bacterium has emerged as a significant public health problem and
      has caused several epidemics in the United States and Europe. Three serotypes
      (1/2a, 1/2b, 4b) of L. monocytogenes are responsible for nearly 95% of all
      reported cases of human listeriosis. L. monocytogenes serotype 4b has caused all
      well-characterized foodborne epidemic outbreaks in North America and Europe
      between 1981 and 1993. However, most of the genetic studies to characterize
      virulence factors of L. monocytogenes have been done by using serotypes 1/2a and
      1/2c. In this investigation, we examined three virulence-associated genes (hly
      encoding listeriolysin, plcA encoding phosphotidylinositol-specific phospholipase
      C, and inlA encoding internalin) of two serotype 4b and two serotype 1/2b
      strains. We chose these virulence-associated genes on the basis of published
      sequence differences among strains from Listeria subgroups containing serotypes
      1/2a and 1/2c versus 4b, respectively. They correspond to sequence homologies
      that include very highly conserved (hlyA), highly conserved (plcA) and mostly
      conserved (inlA). We found by using nucleotide sequence analysis of the hly,
      plcA, and inlA genes, the two L. monocytogenes strains (including a strain
      associated with a foodborne disease outbreak in California in 1985) in this
      study, two serotype 1/2b strains from a study that we recently reported, and
      other similar published data for serotypes 1/2a, 1/2c, and 4b, had a high degree
      of sequence conservation at the gene and protein levels for all three genes.
      However, the sequences for the hly gene of L. monocytogenes strains of serotypes
      1/2b and 4b were more closely related to each other and showed significant
      divergence from serotypes 1/2a and 1/2c. A unique nonsynonymous mutation was
      found in the hly gene of L. monocytogenes isolates that were associated with the
      1985 California outbreak and were the epidemic phage type. When 158 L.
      monocytogenes isolates from the collection at the Centers for Disease Control and
      Prevention were screened, the mutation was found only in one other strain that
      had been isolated in California 3 years before the epidemic. Although the
      California epidemic clone was lactose negative, other L. monocytogenes serotype
      4b isolates that were lactose negative did not possess the unique mutation
      observed in that epidemic clone.

PMID- 9541570
TI  - Percutaneous sensitization with allergens through barrier-disrupted skin elicits
      a Th2-dominant cytokine response.
AB  - We investigated whether percutaneous sensitization with different allergens
      through barrier-disrupted skin regulates the balance of Th1/Th2 cytokine
      expression. When mice were sensitized with the typical hapten picryl chloride
      (PiCl) by a single topical application to intact skin, there was an up-regulation
      in the lymph nodes (LN) of mRNA expression for the Th1 cytokines IL-2 or IFN
      gamma, and for the Th2 cytokine IL-4. In contrast, sensitization with PiCl after
      barrier disruption of the skin down-regulated the expression of mRNA for IFN
      gamma in a tape-stripping number-dependent manner without changing the expression
      of mRNA for IL-4. When mice were sensitized with house dust mite antigens (MA) by
      a single topical application to barrier-disrupted abdominal skin, there was a
      tape-stripping number-dependent up-regulation in the LN of mRNA expression for IL
      4 but not for IL-2 or IFN-gamma. In the LN, mRNA for the IL-4-inducible
      immunoglobulins IgE and IgG1, but not for the IFN-gamma-inducible IgG2a, were up
      regulated after sensitization with MA, while all three immunoglobulin mRNA were
      augmented after PiCl sensitization through intact skin. Antigenic elicitation by
      a topical application of PiCl in aural skin of mice sensitized through intact
      skin consistently increased the expression of mRNA for all three cytokines in the
      challenged skin, whereas elicitation in mice sensitized through barrier-disrupted
      skin decreased the expression of mRNA for IL-2 and IFN-gamma, but not for IL-4.
      Antigenic elicitation by subcutaneous injection of MA in aural skin consistently
      increased the expression of mRNA for IL-4, but not for IL-2 or IFN-gamma in the
      challenged skin. Infiltration of eosinophils in the dermis was more prominent
      following elicitation with MA in mice sensitized through barrier disruption than
      with PiCl in mice sensitized through intact skin. These findings suggest that the
      percutaneous entry of environmental allergens through barrier-disrupted skin is
      strongly associated with the induction of Th2-dominant immunological responses,
      as is seen in atopic dermatitis.

PMID- 9541571
TI  - Absence of B7.1-CD28/CTLA-4-mediated co-stimulation in human NK cells.
AB  - Recent studies have suggested that B7-CD28 interactions provide co-stimulatory
      signals for activation of NK cells. Transduction of the B7.1 (CD80) gene into
      tumor cells has been shown to trigger proliferation and cytotoxicity of murine NK
      cells and a human NK cell line, YT2C2. Therefore, transduction of the B7.1 gene
      into CD80-negative human squamous cell carcinomas of the head and neck (SCCHN)
      and its stable expression was expected to upregulate proliferation and cytotoxic
      activities of human NK cells. However, expression of the B7.1 receptors, CD28 and
      CTLA-4, could not be demonstrated on the surface or in the cytoplasm of normal
      human NK cells, irrespective of the state of their activation. In proliferation
      experiments or various cytotoxicity assays, utilizing highly purified human NK
      cells as responder or effector cells, no enhancement of NK cell generation or
      activity, respectively, by B7.1+ SCCHN was observed relative to non-transduced or
      LacZ gene-transduced SCCHN. In contrast, co-incubation of B7.1+ SCCHN targets
      with human NK cells induced significant inhibition of NK cell growth. Thus, the
      B7.1-CD28/CTLA-4 pathway is not involved in triggering of human adult NK cells.

PMID- 9541572
TI  - Identification of a tissue- and differentiation stage-specific enhancer of the
      VpreB1 gene.
AB  - The VpreB and lambda 5 genes encode proteins that associate non-covalently to
      form the so-called surrogate light (SL) chain. The SL chain complexes with the
      immunoglobulin heavy chain to form the pre-B cell receptor, which plays a
      critical role in B cell development. Expression of the murine SL genes is
      regulated at the level of transcription initiation. Here, we show that a VpreB1
      enhancer is located within the 356 bp immediately upstream of the coding
      sequence. Interestingly, this region exhibits 96% identity to the upstream region
      of VpreB2. Deletion mapping located the enhancer to between positions -214 and 
      47 (+1 is the 5'-most transcription initiation site). The enhancer is tissue and
      differentiation stage specific, and is composed of several DNA elements that are
      important for its activity. We also show that a transcription factor, early B
      cell factor, binds to two such elements, and that at least one of these sites is
      involved in determining enhancer activity.

PMID- 9541573
TI  - Peptide loading onto recycling HLA-DR molecules occurs in early endosomes.
AB  - Presentation of exogenous antigens to MHC class II-restricted T cells can follow
      two different processing pathways. The classical pathway requires newly
      synthesized MHC class II molecules, invariant chain and HLA-DM expression,
      whereas the alternative pathway is independent of protein synthesis, invariant
      chain and HLA-DM. In both cases, MHC class II molecules associate with peptides
      derived from exogenous antigens that have been processed in endocytic
      compartments. Different endosomal/prelysosomal compartments where peptide/MHC
      class II complexes and HLA-DM molecules accumulate have been described. We show
      here that the alternative pathway uses an earlier compartment than the classical
      pathway. Experiments with chemically cross-linked antigen suggest that recycling
      MHC class II molecules present rapidly degraded antigens, leading to a rapid
      immune response to exogenously added influenza virus proteins.

PMID- 9541574
TI  - Jak-STAT pathway is involved in the induction of TNF-beta gene during stimulation
      by IL-2.
AB  - IL-2 is the major regulatory cytokine of the immune system. It plays a key role
      in T cell survival, growth and activation. IL-2 may induce the expression of
      multiple genes including some cytokine genes. The induction of these genes is
      triggered by different signal pathways, one of them being the Jak-STAT signal
      pathway. The genes regulated by this pathway remain to be determined. By studying
      IL-2-inducible genes, we have confirmed that the TNF-beta gene is one of the
      immediate early genes activated by IL-2. By analysis of the DNA sequences around
      180-300 bases upstream of the transcription initiation point of the mouse TNF
      beta gene, we demonstrate that there is a STAT5 binding site which is essential
      to the inducibility of the TNF-beta gene. Furthermore, in BA/F3 cells co
      transfected with the STAT5A gene and IL-2R beta gene, the activation of the TNF
      beta gene promoter by IL-2 was greatly promoted, whereas the TNF-beta gene
      promoter became IL-2-non-inducible if the STAT5A gene was substituted with a
      dominant negative STAT5A, i.e. a C-terminally truncated mutant. Taken together,
      our results show that the Jak-STAT signal pathway is involved in induction of the
      TNF-beta gene in cells stimulated by IL-2.

PMID- 9541575
TI  - Generation or large numbers of immature and mature dendritic cells from rat bone
      marrow cultures.
AB  - We have defined conditions for generating large numbers of dendritic cells (DC)
      in marrow cultures from 10-12-week-old ACI or WF rats. The combination of
      granulocyte-macrophage colony-stimulating factor (GM-CSF) and TNF-alpha, known to
      induce DC from human CD34+ progenitors, was not effective with rat. In contrast,
      GM-CSF plus IL-4 generated DC in high yield, corresponding to 30-40% of the
      initial number of plated marrow cells. The DC proliferated in distinctive
      aggregates, in which most cells had an immature phenotype marked by undetectable
      surface B7 and high levels of MHC class II products within intracellular
      lysosomes. When dislodged and dispersed, the aggregates gave rise to mature
      stellate DC with abundant surface MHC class II and B7, sparse MHC class II-
      lysosomes, and strong T cell-stimulating capacity. Therefore, rat marrow
      progenitors can generate large numbers of immature DC, with abundant
      intracellular MHC class II compartments, and potent, stimulatory, mature DC.

PMID- 9541576
TI  - Differential chronology of TCRADV2 gene use by alpha and delta chains of the
      mouse TCR.
AB  - The genes coding for TCR alpha and delta chains share the same genetic locus
      (TCRA/D). The rules governing the utilization of a V gene with the alpha and
      delta chains have not been established. More specifically, it is not known
      whether the position of a gene within the locus influences its utilization in
      alpha and delta TCR. To elucidate these points, we mapped ADV2 genes in the
      TCRA/D locus of BALB/c mice and analyzed their utilization in TCR alpha and delta
      transcripts from thymi isolated from mice of different ages. Our results show
      that all ADV2 genes can be used by the two chains, but with strikingly different
      patterns. Moreover, ADV2 utilization by the alpha chain proceeds in successive
      concentric waves during development, suggesting a progressive regulation of gene
      accessibility and utilization. These results support independent control of TCRA
      and TCRD gene assembly.

PMID- 9541577
TI  - A TCR alpha chain transgene induces maturation of CD4- CD8- alpha beta+ T cells
      from gamma delta T cell precursors.
AB  - The proportion of CD4- CD8- double-negative (DN) alpha beta T cells is increased
      both in the thymus and in peripheral lymphoid organs of TCR alpha chain
      transgenic mice. In this report we have characterized this T cell population to
      elucidate its relationship to alpha beta and gamma delta T cells. We show that
      the transgenic DN cells are phenotypically similar to gamma delta T cells but
      distinct from DN NK T cells. The precursors of DN cells have neither rearranged
      endogenous TCR alpha genes nor been negatively selected by the MIsa antigen,
      suggesting that they originate from a differentiation stage before the onset of
      TCR alpha chain rearrangements and CD4/CD8 gene expression. Neither in-frame V
      delta D delta J delta nor V gamma J gamma rearrangements are over-represented in
      this population. However, since peripheral gamma delta T cells with functional
      TCR beta gene rearrangements have been depleted in the transgenics, we propose
      that the transgenic DN population, at least partially, originates from the
      precursors of those cells. The present data lend support to the view that
      maturation signals to gamma delta lineage-committed precursors can be delivered
      via TCR alpha beta heterodimers.

PMID- 9541578
TI  - IFN-gamma-induced TNF-alpha is a prerequisite for in vitro production of nitric
      oxide generated in murine peritoneal macrophages by IFN-gamma.
AB  - The effect of IFN-gamma to stimulate formation of nitric oxide (NO) by normal
      murine peritoneal macrophages (M phi) has been found to be completely dependent
      on the ability of IFN-gamma to activate secretion of TNF-alpha. The NO
      stimulatory effect of IFN-gamma was abolished by anti-TNF-alpha antibodies, the
      inhibitory intervention of which could be fully reversed by exogenously supplied
      TNF-alpha. Accordingly, the failure of M phi from C3H/HeJ mice to secrete TNF
      alpha upon stimulation with IFN-gamma was associated with their complete
      incapability to generate NO, unless they were simultaneously treated with IFN
      gamma + TNF-alpha. Collectively, the data document that similar to the NO up
      regulatory action of other cytokines, the effect of IFN-gamma is not independent,
      but depends on a synergistic cooperation with the self-produced TNF-alpha. The
      findings thus indicate that a widespread opinion claiming that IFN-gamma per se
      is able to stimulate biosynthesis of NO needs revision.

PMID- 9541579
TI  - IL-4 mRNA transcription is induced in mouse bone marrow-derived mast cells
      through an MHC class II-dependent signaling pathway.
AB  - We have previously shown that mouse bone marrow-derived mast cells (BMMC) can
      process and present immunogenic peptides to CD4 T cells. Here, we report on a T
      cell-dependent MHC class II-mediated mast cell activation resulting in IL-4
      transcription and protein release. Presentation of optimal doses of ovalbumin
      peptide 323-339 resulted in IL-2 production by a specific T cell hybridoma and
      increase in IL-4 mRNA transcription in mast cells. IL-4 mRNA transcription
      increased by 200-fold in mast cells treated in IL-3/IL-4/granulocyte-macrophage
      colony-stimulating factor (high presenters) whereas only a tenfold increase or no
      increase were obtained with IL-3/IL-4/IFN-gamma- or IL-3-treated mast cells (low
      presenters), respectively. Induction of IL-4 mRNA transcription in purified mast
      cells by direct ligation of MHC class II molecules, using anti-I-A and anti-I-E
      coated beads, indicates that MHC class II molecules are critical in this
      signaling pathway. However, when compared to T cells, anti-MHC class II-coated
      beads were less efficient, indicating a potential role of accessory molecules in
      this mast cell activation process. IgE-independent IL-4 production by mast cells
      as a result of cognate interaction with CD4 T cells could be critical for the
      development of type 2 responses. This novel mechanism may contribute to the
      induction and/or amplification of specific IgE-mediated allergic responses.

PMID- 9541580
TI  - A combination of stem cell factor and granulocyte colony-stimulating factor
      enhances the growth of human progenitor B cells supported by murine stromal cell
      line MS-5.
AB  - We have developed a long-term culture system using the murine bone marrow stromal
      cells MS-5 to support the growth of progenitor B cells with CD34-, CD10+, CD19+,
      and cytoplasmic mu chain (C mu)-negative surface phenotype from human CD34+ cells
      purified from umbilical cord blood (CB). When 10(3) CD34+ cells/well were seeded
      on MS-5 stromal cells at the beginning of culture in the absence of exogenously
      added cytokines, progenitor B cells first appeared after 14 days, and the maximal
      cell production was achieved during the 6th week of culture. Intriguingly, the
      addition of recombinant human stem cell factor (rhSCF) and granulocyte colony
      stimulating factor (rhG-CSF), but not rhIL-7, strikingly enhanced the growth of
      progenitor B cells from CB CD34+ population cultured on MS-5 stromal cells. The
      culture of progenitor B cells could be maintained until the 6th week of culture
      when some cells were revealed to have a C mu phenotype, and a small number of
      cells had immunoglobulin mu chain on their cell surface in the presence of both
      rhSCF and rhG-CSF. When CD34+ cells were cultured physically separated from the
      stromal layer by membrane, supportive effects of MS-5 stromal cells for the
      growth of progenitor B cells were not observed. These results suggest that the
      present culture system could generate progenitor B cells to proliferate from CB
      CD34+ cells, that some of these progenitor B cells could differentiate into
      immature B cells in conjunction with rhSCF and rhG-CSF, and that a species-cross
      reactive membrane-bound factor(s), which stimulates early human B lymphopoiesis,
      may exist in MS-5 stromal cells. Further studies are required to investigate the
      mechanism how rhG-CSF acts on progenitor B cells to allow their proliferation and
      differentiation.

PMID- 9541581
TI  - Expression and co-stimulatory function of B7-2 on murine CD4+ T cells.
AB  - Co-stimulatory signals mediated by the interaction of B7-1/B7-2 with CD28 are
      important for the activation of CD4+ T cells stimulated with antigen on antigen
      presenting cells. There are controversies about the expression and function of B7
      1/B7-2 on CD4+ T cells. The aim of this study was to analyze the expression of B7
      1/B7-2 on naive and memory CD4+ T cells and the co-stimulatory function in the
      activation of naive CD4+ T cells stimulated by TCR ligation. Present results
      indicate that memory CD4+ T cells express B7-2 molecules on their surface,
      whereas naive CD4+ T cells do not. Neither memory nor naive CD4+ T cells
      expressed B7-1 molecule on their surface, although B7-1 mRNA was faintly
      expressed in memory T cells. B7-2 molecules expressed on memory T cells co
      stimulated CD4+ naive T cells stimulated with plate-coated anti-CD3 to produce IL
      2. Naive CD4+ T cells were shown to express B7-2 after co-stimulation with B7-2
      and TCR ligation, because the naive T cells stimulated with anti-CD3 and B7-2CHO
      expressed B7-2 on their surface, although it remained to be studied whether the
      co-stimulation with B7-2 directly induced B7-2 expression on naive T cells. Our
      present results indicate that memory CD4+ T cells play some role in the
      activation of naive CD4+ T cells through the co-stimulation with B7-2 molecules.

PMID- 9541582
TI  - Ceramide-independent CD28 and TCR signaling but reduced IL-2 secretion in T cells
      of acid sphingomyelinase-deficient mice.
AB  - Ceramide generated by lysosomal acid sphingomyelinase (aSMase) has been proposed
      to contribute to CD28 co-stimulatory signaling pathways. We used an aSMase
      deficient mouse line (asmase-/-) to elucidate the role of the aSMase in
      splenocytes stimulated with either a combination of anti-CD3 and anti-CD28
      antibodies, the lectin concanavalin A (Con A) or the superantigen staphylococcal
      enterotoxin B. All stimuli were shown to induce IL-2 expression, Con A
      additionally triggered the expression of high-affinity IL-2 receptor. However, in
      asmase-/- mice secretion of IL-2 was significantly reduced, whereas the
      intracellular IL-2 levels were elevated. Proliferation of anti-CD3/anti-CD28 or
      Con A-stimulated aSMase-deficient splenocytes was reduced up to 50% after 72 h in
      comparison to wild-type cells. We conclude that ceramide generated by aSMase is
      not involved in CD28 signal transduction, but rather a perturbation of the
      secretory system is responsible for the impaired proliferation of aSMase
      deficient splenocytes.

PMID- 9541583
TI  - Human 4-1BB regulates CD28 co-stimulation to promote Th1 cell responses.
AB  - Our present study provides evidence that the 4-1BB signal is critical to CD28 co
      stimulation in maintaining T cell activation when CD28 has been down-regulated
      because of repeated stimulation. The 4-1BB signal synergized with CD28 co
      stimulation by lowering the threshold of anti-CD28 required to sustain
      proliferation and IL-2 production. The 4-1BB signal also modulated CD28-mediated
      cytokine profiles by markedly enhancing Th1 but suppressing Th2-type cytokine
      production. The 4-1BB signal generated Th1-type cells, as identified by
      intracellular IFN-gamma production. IFN-gamma induction was detected
      preferentially in 4-1BB-expressing cells, but not in those expressing CD30. 4-1BB
      and CD30 were induced in both CD4+ and CD8+ cells, but the location of the two
      molecules was mutually exclusive in each T cell subset. Our study suggests that
      the 4-1BB signal regulates CD28 co-stimulation in the targeted subset cells to
      favor Th1 development and maintain long-term cell growth.

PMID- 9541584
TI  - Activation of caspase-3-like enzymes in non-apoptotic T cells.
AB  - The activation of the caspase family of cysteine proteases is a key step in the
      implementation of apoptotic cell death leading to further downstream effects such
      as DNA fragmentation. In cultured tumor cells, caspase activity appears only when
      cells are undergoing apoptosis. Here we show that human and murine T lymphocytes
      acquire high intracellular activities of cell death-specific caspases upon
      activation by mitogens and IL-2 without evidence that apoptosis is proceeding.
      The highest activity is seen when cells are mitogen activated for 3 days. On a
      per cell basis, caspase activity in activated T cells is much higher than in
      tumor cells induced to undergo apoptosis. In the presence of exogenously added IL
      2 cells stay alive and maintain a high level of caspase activity while IL-2
      withdrawal results in cell death and decline of caspase activity. Caspase
      activity can also be measured in extracts from spleen and lymph nodes from mice
      injected with superantigen. While in tumor cell lines caspase activity correlates
      with cleavage of poly(ADP)-ribose polymerase (PARP) and DNA fragmentation, in
      activated T cells cleavage products of cellular PARP can be detected whereas DNA
      fragmenting activity appears only upon IL-2 withdrawal which coincides with cell
      death. These data show that caspase activation in intact cells does not
      necessarily lead to cell death and argue for a checkpoint in the apoptotic
      pathway downstream of caspases. Furthermore, they provide a molecular correlate
      for the high susceptibility of activated T cells for apoptosis.

PMID- 9541585
TI  - CD40 ligation and IL-4 use different mechanisms of transcriptional activation of
      the human lymphotoxin alpha promoter in B cells.
AB  - We have previously shown that both CD40 ligation and IL-4 induce lymphotoxin
      alpha (LT alpha) expression in B cells. We generated a series of truncations of
      the LT alpha upstream region (-915 to +7 bp) and examined their ability to drive
      expression of a luciferase (LUC) reporter gene in B cells. The CD40-responsive
      promoter region of LT alpha was mapped to the region spanning -120 to -52 bp.
      This region contains an NF-kappa B site (-99 to -89 bp) which was shown to form a
      complex with nucleoproteins from CD40-stimulated B cells that contained the
      p50/p65 subunits of NF-kappa B. Mutation of the NF-kappa B site within the -356
      to +7 bp region of the LT alpha gene completely abolished its capacity to drive
      transcription of the LUC gene in response to stimulation with CD40, but not to IL
      4. The IL-4-responsive promoter region of LT alpha was mapped to the region
      spanning -265 to -185 bp. This region contains a site for binding to signal
      transducers and activators of transcription (STAT) proteins (-197 to -189 bp).
      This site was shown to form a complex with nucleoproteins from IL-4-stimulated B
      cells that contained STAT6. Mutation of the STAT site within the -356 to +7 bp
      region of the LT alpha gene completely abolished its capacity to drive
      transcription of the LUC gene in response to IL-4, but not to anti-CD40. These
      results demonstrate that CD40 and IL-4 use distinct mechanisms, namely activation
      of NF-kappa B and STAT6, respectively, to activate transcription of the LT alpha
      gene in B cells.

PMID- 9541586
TI  - Calnexin expression does not enhance the generation of MHC class I-peptide
      complexes.
AB  - We investigated the requirement for calnexin in the biogenesis of MHC class I
      molecules. Mutant human cells lacking calnexin were infected with recombinant
      vaccinia viruses encoding mouse MHC class I molecules, Kd, Kb, Kk, Dd, Db, and
      Ld. Flow cytometry indicated that each of the six MHC class I allomorphs was
      transported to the cell surface at similar rates in calnexin-deficient cells and
      transfectants expressing calnexin. For Kb and Kd, the calnexin-independent
      biogenesis occurred regardless of whether the MHC class I molecules contained
      human or mouse beta 2-microglobulin. Also addressed was the effect of calnexin on
      the surface expression of Kb molecules bearing the immunodominant peptide from
      ovalbumin (OVA257-264). This was detected with a recently described monoclonal
      antibody specific for the Kb/peptide complex. Calnexin expression had no
      significant effect on the formation of Kb/peptide complexes generated from full
      length OVA, cytosolic OVA257-264, or endoplasmic reticulum-targeted OVA257-264,
      which was expressed in the presence of the herpes simplex virus ICP47 protein to
      ensure detection of TAP-independent peptide-MHC class I complexes. Complementary
      results were obtained with TAP-independent formation of Kd/ peptide complexes.
      These findings indicate that calnexin is not required for the efficient assembly
      of MHC class I molecules with TAP-dependent or independent peptides.

PMID- 9541587
TI  - Differential regulation of human T cell cytokine patterns and IgE and IgG4
      responses by conformational antigen variants.
AB  - Bee venom phospholipase A2 (PLA) represents the major allergen and antigen in
      allergic and non-allergic individuals sensitized to bee sting. We have studied
      specific activation of peripheral T cells by different structural and
      conformational variants of PLA and secretion of cytokines regulating IgE and IgG4
      antibody (Ab) formation. PLA molecules expressing the correctly folded tertiary
      structure, which show high affinity to membrane phospholipids and were recognized
      by Ab from bee sting allergic patients, induced high IL-4, IL-5 and IL-13
      production in peripheral blood mononuclear cell cultures. In contrast, non
      refolded recombinant PLA (rPLA) and reduced and alkylated native PLA (nPLA)
      induced more IFN-gamma and IL-2 and higher proliferative responses. Differences
      in proliferation and cytokine patterns among correctly folded and non-refolded
      PLA resulted from conformation-dependent involvement of different antigen
      presenting cell (APC) types. Antigen (Ag)-presenting B cells recognized PLA only
      in its natural conformation, stimulated Th2 type cytokines and induced IgE Ab.
      Non-refolded PLA was recognized, processed and presented exclusively by monocytes
      and induced a Th1 dominant cytokine profile leading to IgG4 production by B
      cells. The possibility that production of particular cytokine patterns and Ig
      isotype was influenced by the enzymatic activity of PLA was excluded by using
      enzymatically inactive H34Q point-mutated, refolded rPLA. These findings
      demonstrate the decisive role of specific Ag recognition by different APC,
      depending on structural features, membrane phospholipid binding property and the
      existence of conformational B cell epitopes, in the differential regulation of
      memory IgE and IgG4 Ab. Furthermore, they show that a change from IgE-mediated
      allergy to normal immunity against a major allergen can be induced by rPLA
      variants that are not recognized by specific Ab and B cells but still carry the T
      cell epitopes. These features may enable new applications for safer
      immunotherapy.

PMID- 9541588
TI  - A fundamental difference in the capacity to induce proliferation of naive T cells
      between CD28 and other co-stimulatory molecules.
AB  - T cell activation requires two signals: a signal from the TCR and a co
      stimulatory signal provided by antigen-presenting cells (APC). In addition to
      CD28, multiple molecules on the T cell have been described to deliver co
      stimulatory signals. Here, we investigated whether there exist quantitative or
      qualitative differences in the co-stimulatory capacity between CD28 and other
      molecules. Anti-CD28 monoclonal antibody (mAb) and mAb against CD5, CD9, CD2,
      CD44 or CD11a all induced activation of naive T cells in the absence of APC when
      co-immobilized with a submitogenic dose of anti-CD3 mAb. [3H]Thymidine
      incorporation determined 2 days after co-stimulation was all comparable. In
      contrast to progressive T cell proliferation induced by CD28 co-stimulation, co
      stimulation by other T cell molecules led to a decrease in viable cell recovery
      along with the induction of apoptosis of once activated T cells. This was
      associated with a striking difference in IL-2 production; CD28 co-stimulation
      induced progressively increasing IL-2 production, whereas co-stimulation by other
      molecules produced limited amounts of IL-2. Addition of recombinant IL-2 to the
      latter cultures corrected the induction of apoptosis, resulting in levels of
      cellular proliferation comparable to those observed for CD28 co-stimulation.
      These results indicate that a fundamental difference exists in the nature of co
      stimulation between CD28 and other molecules, which can be evaluated by the
      levels of IL-2 production, but not simply by [3H]thymidine incorporation.

PMID- 9541589
TI  - Chronic parvovirus B19 infection induces the production of anti-virus antibodies
      with autoantigen binding properties.
AB  - Human parvovirus B19 infection in adults shows some clinical features similar to
      those found in autoimmune connective tissue diseases. To better clarify the
      relationship between viral infection and autoimmunity, we have evaluated the
      ability of anti-parvovirus antibodies to specifically recognize autoantigens in
      ten patients with chronic symmetric arthritis resembling rheumatoid arthritis or
      with recurrent episodes of arthritis and cutaneous manifestations and persistence
      of specific IgM antibodies against B19 parvovirus. We synthetized a 24-amino acid
      immunodominant peptide corresponding to a part of the virus protein 1 and virus
      protein 2 overlapping region. The peptide has been used to test patients' sera at
      different time points with an enzyme-linked immunosorbent assay (ELISA) and to
      purify anti-virus antibodies by affinity chromatography on a peptide-Sepharose
      column. Eluted immunoglobulins recognized the B19 peptide in both direct and
      competitive ELISA. Affinity-purified anti-parvovirus antibodies were then tested
      on a panel of autoantigens including human keratin, collagen type II,
      thyreoglobulin, single-strand (ss)DNA, cardiolipin and ribonucleoprotein antigen
      Sm. Eluted antibodies specifically recognized keratin, collagen type II, ssDNA
      and cardiolipin. Autoantibody activity was not detected in the immunoglobulin
      fraction after complete removal of anti-peptide antibodies and in antibodies
      eluted from normal donors. Epstein-Barr virus-transformed cell clones obtained
      from two subjects produced antibodies which simultaneously recognize the viral
      peptide and several autoantigens. To further confirm the role of the virus in
      inducing an autoantibody response, eight BALB/c mice were immunized with the
      viral peptide coupled to a carrier protein. Autoantibody activity against
      keratin, collagen II, cardiolipin and ssDNA was detected in six of the eight mice
      which developed a strong anti-virus response. Together, these data indicate that
      B19 parvovirus may be linked to the induction of an autoimmune response.

PMID- 9541590
TI  - The threshold for autoimmune T cell killing is influenced by B7-1.
AB  - The concept that naive CD4+ and CD8+ T cells require co-stimulatory signals for
      activation and proliferation is well documented. Less clear is the need for co
      stimulation during the effector phase of the T cell response. Here we examined
      the influence of B7-1 (CD80) during the effector phase of an autoimmune response
      to pancreatic islets using transgenic mouse lines which expressed B7-1 in either
      all or only some of their beta cells ("confluent" or "patchy" RIP-B7-1 mice).
      Transgenic expression of B7-1 in normal mouse islets that co-expressed the pro
      inflammatory cytokine, IL-2, resulted in early spontaneous autoimmunity. Islets
      with IL-2 and "confluent" B7-1 expression were destroyed whereas islets with IL-2
      and "patchy" B7-1 expression showed selective killing of the B7-1+ beta cells.
      Islet-reactive T cells, circulating in the RIP-B7-1/IL-2 mice, rejected syngeneic
      islet grafts, but only if these expressed B7-1. Introduction of the B7-1
      transgene into the nonobese diabetic (NOD) genetic background likewise resulted
      in early spontaneous autoimmunity, but splenocytes from the diabetic animals
      could only transfer diabetes to NOD scid recipients that expressed B7-1 on their
      beta cells. In both these transgenic models, therefore, islet destruction
      required continuous B7-1 expression by target beta cells. Thus, although the
      normal repertoire contains T cells with potential islet reactivity, these T cells
      remain harmless because parenchymal cells like the beta cell cannot normally
      express B7-1. Our results also have implications for tumor immunotherapy in that
      the ability of T cells to kill poorly immunogenic targets may be dependent upon
      B7-1 expression by the target cell itself.

PMID- 9541591
TI  - The chemokine receptor CXCR3 mediates rapid and shear-resistant adhesion
      induction of effector T lymphocytes by the chemokines IP10 and Mig.
AB  - Integrin-mediated adhesion to the vascular endothelium is an essential step in
      leukocyte diapedesis. We show that the chemokines 10-kDa inflammatory protein
      (IP10) and monokine induced by IFN (Mig) induce rapid and transient adhesion of
      human IL-2-stimulated T lymphocytes (IL-2 T cells) to immobilized integrin
      ligands through their receptor CXCR3, which is selectively expressed on activated
      T cells. Induction of adhesion by IP10 and Mig was already observed at
      subnanomolar concentrations and was maximal at 5-10 nM, resulting in three- to
      sixfold increase in adhesion of IL-2 T cells over background. No effect was seen
      with resting naive/memory T cells which lack CXCR3 and migration responses to
      IP10 and Mig. Both chemokines are produced in human umbilical vein endothelial
      cells (HUVEC) upon stimulation with IFN-gamma and TNF-alpha. These chemokines
      induce IL-2 T cell adhesion also when captured on the surface of endothelial
      cells. Under conditions of flow, IL-2 T cells roll and rapidly adhere to IP10/Mig
      expressing HUVEC, and anti-CXCR3 mAb treatment reduces arrest and firm adhesion.
      This is the first study that shows chemokine-induced adhesion in activated
      memory/effector T cells which represent the fraction of T cells that are
      selectively mobilized in inflammation. The critical role of IFN-gamma as inducer
      of IP10/Mig production in HUVEC indicates that these chemokines are essential
      mediators of effector T cell recruitment to IFN-gamma-dependent pathologies.

PMID- 9541592
TI  - Differential regulation of TRAIL and CD95 ligand in transformed cells of the T
      and B lymphocyte lineage.
AB  - TRAIL (APO-2 ligand) and CD95L (CD95/APO-1/Fas ligand) share the highest homology
      among the TNF family members and the ability to induce apoptosis. These
      similarities raise the issue of a potential functional redundancy between the two
      ligands. We have previously shown that CD95L-resistant cells may be sensitive to
      TRAIL, even though apoptosis induced by both ligands is blocked by caspase
      inhibitors. Here we investigated TRAIL protein expression in cells of T and B
      origin and compared its regulation of expression with that of CD95L. A rabbit
      antibody (Ab) to a peptide sequence in the extracellular region of TRAIL
      identified recombinant TRAIL (rTRAIL) produced by Sf9 cells as a protein of
      approximately 32-33 kDa and soluble rTRAIL as a 19-20-kDa protein. In human and
      mouse cells, the Ab identified a 33-34-kDa and an additional 19-20-kDa protein
      only in human cells. Both transformed cells of the T and B lymphocyte lineage
      were found to react with the anti-TRAIL Ab by immunoblot analysis and surface
      staining. The majority of the cells analyzed co-expressed TRAIL and CD95L. Two
      cell lines showed a mirror-pattern, one being TRAILhigh CD95Llow and the other
      TRAILlow CD95Lhigh, thus suggesting the existence of a cell type-specific
      regulation of expression of the two ligands. Differently from CD95L, surface
      TRAIL was not up-regulated by any of the metalloprotease inhibitors tested,
      independently of the cell type analyzed. Conversely, reactivity with the anti
      TRAIL but not with the anti-CD95L Ab was enhanced by cysteine protease
      inhibitors. An in vitro cleavage assay showed that generation of soluble rTRAIL
      was dependent on the functional activity of cysteine proteases, as it was blocked
      by leupeptin and E64 but not by the metalloprotease inhibitor 1,10
      phenanthroline. Thus, even though TRAIL and CD95L share structural and functional
      properties, they have unique properties as they differ in their regulatory
      pathways, i.e. cell-type-dependent expression and sensitivity to protease
      inhibitors.

PMID- 9541593
TI  - P-selectin binds to bacterial lipopolysaccharide.
AB  - Multiple organ failure associated with disseminated intravascular coagulation is
      a frequent complication in septic shock patients. Accumulation of platelets and
      neutrophils in the organs contributes to the manifestation of lipopolysaccharide
      (LPS)-induced organ failure. Although a direct interaction between LPS and
      platelets is well documented, the nature of the surface receptor for LPS on
      platelets is unknown. In this article we show that P-selectin is a receptor for
      LPS. The binding of LPS to P-selectin is independent of Ca2+, and is blocked by
      antibodies to P-selectin, lipid A and fucoidan. Platelets pre-treated with
      thrombin showed fourfold higher binding of fluorescein isothiocyanate (FITC)
      conjugated LPS compared to untreated platelets and the binding of FITC-conjugated
      LPS to platelets was blocked in the presence of anti-P-selectin antibodies. It is
      likely that the binding of LPS via P-selectin on activated platelets or
      epithelium could have a significant role in the pathophysiology of organ failure
      in septic shock.

PMID- 9541594
TI  - Polyreactive antigen-binding B cells are the predominant cell type in the newborn
      B cell repertoire.
AB  - Polyreactive antibodies bind to a variety of different self and non-self
      antigens. The B cells that make these antibodies express the polyreactive lg
      receptor on their surface. To determine the frequency of polyreactive antigen
      binding B cells in peripheral blood, we incubated two different antigens, one
      (insulin) labeled with fluorescein isothiocyanate and the other (beta
      galactosidase) with phycoerythrin, with peripheral B cells. The percentage of
      cells that bound these antigens was determined with the fluorescence-activated
      cells sorter. Approximately 21% of adult B cells bound insulin, 28% bound beta
      galactosidase, and 11% bound both antigens. In contrast to B cells in the adult
      repertoire, 49% of B cells in cord blood bound insulin, 54% bound beta
      galactosidase, and 33% bound both antigens. The properties of polyreactive
      antigen-binding B cells in adult and cord blood were similar, except for the fact
      that almost all the polyreactive antigen-binding B cells in cord blood were CD5
      positive (93%), whereas only 40% of the polyreactive antigen-binding B cells in
      adult peripheral blood were CD5 positive, indicating that the CD5 marker is not
      directly linked to polyreactivity. The percentage of polyreactive antigen-binding
      B cells in patients with Sjogren's syndrome, systemic lupus erythematosus and
      rheumatoid arthritis was equal to or slightly below that found in the normal
      adult B cell repertoire. It is concluded that polyreactive antigen-binding B
      cells are a major constituent of the normal adult B cell repertoire and are the
      predominant cell type in the newborn B cell repertoire.

PMID- 9541595
TI  - LPAM-1 (integrin alpha 4 beta 7)-ligand binding: overlapping binding sites
      recognizing VCAM-1, MAdCAM-1 and CS-1 are blocked by fibrinogen, a fibronectin
      like polymer and RGD-like cyclic peptides.
AB  - The alpha 4 integrin LPAM-1 (alpha 4 beta 7) mediates lymphocyte attachment
      within the extracellular matrix (ECM) by adhering to the connecting segment (CS)
      1 site of fibronectin (FN). Here we reveal that very late antigen (VLA)-4 LPAM-1+
      T cell lymphoma TK-1 cells bind via LPAM-1 to multiple copies of the RGD sequence
      engineered within an FN-like polymer. Further, the small conformationally
      restrained RGD-like cyclic peptides 1-adamantaneacetyl-Cys-Gly-Arg-Gly-Asp-Ser
      Pro-Cys and Arg-Cys-Asp-thioproline-Cys inhibit the adhesion of TK-1 cells to
      immobilized CS-1 peptide, and to endothelial counterreceptors for LPAM-1, namely
      mucosal addressin cell adhesion molecule (MAdCAM)-1 and vascular cell adhesion
      molecule (VCAM)-1. Spontaneous adhesion of the VLA-4- LPAM-1+ B lymphoma cell
      line RPMI 8866 to CS-1 was likewise inhibited, confirming a previously
      undocumented ability of LPAM-1 to recognize the RGD tripeptide. The RGD-binding
      site in LPAM-1 either overlaps or is identical to sites required for interaction
      with MAdCAM-1, VCAM-1, and the CS-1. The binding of LPAM-1 and VLA-4 to RGD
      containing ligands may have relevance in vivo given that fibrinogen at
      physiological concentrations is able to partially block the binding of TK-1 cells
      to MAdCAM-1. Hence fibrinogen and other vascular RGD-containing proteins may have
      mild anti-inflammatory activity required for maintaining effective homeostasis,
      analogous to the anti-thrombogenic activity of the vascular endothelium.

PMID- 9541596
TI  - CD16-mediated activation of phosphatidylinositol-3 kinase (PI-3K) in human NK
      cells involves tyrosine phosphorylation of Cbl and its association with Grb2,
      Shc, pp36 and p85 PI-3K subunit.
AB  - Phosphatidylinositol 3-kinase (Pl-3K) plays a key role in several cellular
      processes, including mitogenesis, apoptosis, actin reorganization and vesicular
      trafficking. The molecular events involved in its activation have not been fully
      elucidated and several reports indicate that a key event for enzyme activation is
      the interaction of the SH2 domains of the p85 regulatory subunit of Pl-3K with
      tyrosine-phosphorylated proteins. In this study, we investigated the involvement
      of the product of the proto-oncogene c-Cbl in the activation of Pl-3K triggered
      by CD16 in human NK cells and the possible mechanisms leading to Pl-3K
      recruitment to the plasma membrane. Our results indicate that stimulation of NK
      cells through CD16 results in a rapid tyrosine phosphorylation of Cbl, which is
      constitutively associated with Grb2 and forms an activation-dependent complex
      with the p85 subunit of Pl-3K. In addition, we detected the presence of the Grb2
      associated tyrosine-phosphorylated p36 and Shc proteins in anti-Cbl and anti-p85
      immunoprecipitates from CD16-stimulated NK cell lysates. Upon CD16 stimulation,
      Pl-3K activity was found associated with Cbl and to a lesser extent with Grb2 and
      Shc as well as with the zeta chain of the CD16 receptor complex. Overall these
      results suggest that the formation of a complex containing either Shc or pp36
      associated with Grb2, Cbl and the p85 subunit of Pl-3K is one of the major
      mechanisms which might couple CD16 to the Pl-3K pathway in NK cells.

PMID- 9541597
TI  - Isolation of processed, H-2Kb-binding ovalbumin-derived peptides associated with
      the stress proteins HSP70 and gp96.
AB  - Stress-induced proteins or heat shock proteins (HSP) of 96 kDa mass (gp96) and 70
      kDa mass (HSP70) have been shown previously to elicit specific immunity to tumors
      from which they are isolated. This immunity is dependent on CD8+ cytotoxic T
      cells which are readily primed in vivo by immunization with HSP. The immunization
      capacity of HSP relies on their ability to bind antigenic peptides. Here we show
      that HSP70 and gp96 preparations purified from the ovalbumin (OVA)-transfected
      cell line E.G7 are associated with processed H-2Kb-binding peptides which contain
      the major H-2Kb-associated epitope SIINFEKL (OVA257-264). Our data show for the
      first time in the well-defined OVA antigen system that not only endoplasmic
      reticulum-resident HSP, like gp96, are associated with processed antigenic
      peptides but that also the cytosolic HSP70 protein forms complexes with major
      finally processed MHC-binding epitopes.

PMID- 9541598
TI  - Characterization of mouse mast cell protease-8, the first member of a novel
      subfamily of mouse mast cell serine proteases, distinct from both the classical
      chymases and tryptases.
AB  - Using a recently developed PCR-based strategy, a cDNA encoding a novel mouse mast
      cell (MC) serine protease (MMCP-8) was isolated and characterized. The MMCP-8
      mRNA contains an open reading frame of 247 amino acids (aa), divided into a
      signal sequence of 18 aa followed by a 2-aa activation peptide (Gly-Glu) and a
      mature protease of 227 aa. The mature protease has an M(r) of 25072, excluding
      post-translational modifications, a net positive charge of +12 and six potential
      N-glycosylation sites. MMCP-8 showed a high degree of homology with mouse
      granzyme B in the critical regions for determining substrate cleavage
      specificity, indicating that MMCP-8, similar to granzyme B, preferentially
      cleaves after Asp residues. A comparative analysis of the aa sequence of MMCP-8
      with other hematopoietic serine proteases shows that it is more closely related
      to cathepsin G and T cell granzymes than to the MC chymases. We therefore
      conclude that MMCP-8 belongs to a novel subfamily of mouse MC proteases distinct
      from both the classical chymases and tryptases. Southern blot analysis of BALB/c
      genomic DNA indicated that only one MMCP-8 gene (or MMCP-8 like gene) is present
      in the mouse genome. Northern blot analysis of rodent hematopoietic cell lines
      revealed high levels of MMCP-8 mRNA in a mouse connective tissue MC-like tumor
      line. However, MMCP-8 mRNA could not be detected in mouse liver, intestine, lung
      or ears, indicating very low expression in normal tissues. Analysis of the
      expression of different MMCP in the tissues of Schistosoma mansoni-infected
      BALB/c mice showed a strong increase in MMCP-8 levels in the lungs but not in the
      intestines of infected animals, suggesting the presence of a novel subpopulation
      of MC in the lungs that expressed MMCP-8, either alone or in combination with
      MMCP-5 and carboxypeptidase A. The dramatic increase in MMCP-1 and MMCP-2 levels
      but not of MMCP-8 in the intestines of parasitized animals also shows that MMCP-8
      is not expressed in mucosal MC in the mouse. This latter is in clear contrast to
      what has been observed in the rat where the MMCP-8 homologues, RMCP-8, -9 and 
      10, can be considered as true mucosal MC proteases.

PMID- 9541599
TI  - Efficient presentation of endogenous superantigen by H-2Aq.
AB  - Endogenous superantigens encoded by mouse mammary tumor viruses associate with
      MHC class II and interact with T cells bearing particular V beta gene segments. H
      2E is more efficient at presentation than H-2A, indeed Aq has not been shown to
      be capable of presenting endogenous superantigens. Atypically, the superantigen
      vSAG-3 encoded by Mtv-3 is presented efficiently in non-obese diabetic (H-2g7)
      mice by H-2A; we have examined the independent contributions of vSAG-3 and Ag7 to
      this process. Ag7 was not found to have a more general ability to efficiently
      present endogenous superantigens other than Mtv-3. Examination of Mtv-3-mediated
      thymic deletion of V beta 3+ thymocytes in the presence of H-2q additionally
      demonstrated the efficient presentation of vSAG-3 by Aq. Interaction of vSAG-3
      with Aq and Ag7 is likely to reflect the unique sequence of Mtv-3 within the
      second polymorphic region previously implicated in MHC class II binding. The
      demonstration that mouse endogenous superantigens can be presented by a wider
      range of MHC haplotypes than previously thought is further evidence for their
      immunological impact on the mouse population.

PMID- 9541600
TI  - Cell division number regulates IgG1 and IgE switching of B cells following
      stimulation by CD40 ligand and IL-4.
AB  - CD40 ligand (CD40L) and IL-4 are sufficient to induce resting murine B cells to
      divide and switch isotypes from IgM and IgD to IgG1 and IgE. Tracking of cell
      division following (5- and 6) carboxyfluorescein diacetate succinimidyl ester
      (CFSE) labeling revealed that B cells expressed IgG1 after three cell divisions,
      and IgE after five. The probability of isotype switching at each division was
      independent of both time after stimulation and of the dose of CD40L. IL-4
      concentration regulated the number of divisions that preceded isotype switching.
      Loss of surface IgM and IgD was also related to cell division and appeared to be
      differentially regulated. B cell proliferation was typically asynchronous with
      the proportion of cells in consecutive divisions being markedly affected by the
      concentration of CD40L and IL-4. Simultaneous (5-bromo)-2'-deoxyuridine labeling
      and CFSE staining revealed that B cells in each division cycle were dividing at
      the same rate. Therefore, division cycle asynchrony resulted from dose-dependent
      variation in the time taken to enter the first division cycle. These results
      suggest that T-dependent B cell expansion is linked to predictable functional
      changes that may, in part, explain why IgE is produced in response to prolonged
      antigenic stimulation.

PMID- 9541601
TI  - Decay-accelerating factor is a component of subendothelial extracellular matrix
      in vitro, and is augmented by activation of endothelial protein kinase C.
AB  - The vasculature is protected from complement activation by regulatory molecules
      expressed on endothelial cells. However, complement fixation also occurs on
      subendothelial extracellular matrix (ECM) in vitro, and is initiated simply by
      retraction or removal of overlying cells. To investigate mechanisms controlling
      vascular complement activation, we examined subendothelial ECM for the presence
      of complement regulatory proteins. Decay-accelerating factor (DAF) was found on
      both human umbilical vein endothelial cells (HUVEC) and in their ECM; in
      contrast, membrane cofactor protein was found only on cells. ECM and HUVEC DAF
      were distinguishable based on several properties. While HUVEC DAF is anchored to
      cell membranes by a phospholipase C-sensitive glycosylphosphatidylinositol
      linkage. DAF was removed from ECM only by proteolytic digestion. Cytokines (TNF
      alpha, IL-1 beta, IL-4) increased HUVEC DAF expression, but had minimal effect on
      ECM DAF; in contrast, phorbol 12-myristate 13-acetate (PMA) and wheat germ
      agglutinin markedly increased DAF on both HUVEC and ECM. The effect of PMA was
      mediated by activation of protein kinase C. The complement regulatory potential
      of ECM DAF was assessed by evaluating the effect of DAF-neutralizing antibodies
      on C3 deposition on HUVEC ECM, as well as on HeLa cell ECM, which had a
      considerably higher DAF content. DAF blockade enhanced C3 deposition on HeLa ECM,
      but had no effect on HUVEC ECM. As ECM DAF is likely to be immobile, i.e. able to
      interact only with C3 convertases forming in the immediate vicinity, its ability
      to regulate complement activation may be particularly density dependent, and
      contingent on endothelial-dependent up-regulation.

PMID- 9541602
TI  - Secretory immune system of the duck (Anas platyrhynchos). Identification and
      expression of the genes encoding IgA and IgM heavy chains.
AB  - IgA has not previously been identified in waterfowl. Studies instead revealed
      physical and antigenic similarities between duck bile immunoglobulin (Ig) and
      serum IgM. Here, a differential screening approach was used to clone, from a duck
      spleen library, the cDNA encoding the heavy (H) chains of IgM and the Ig,
      identified here as IgA, occurring in duck secretions. Phylogenetic comparisons of
      inferred amino acid sequences of entire H chain constant (C) regions and of
      individual domains revealed that the duck mu chain was closest to chicken mu (54%
      overall identity), and duck alpha was closest to chicken alpha (50% identity).
      Comparison of the mu and alpha C regions revealed areas of up to 65% amino acid
      similarity within the C4 domains, accounting for the previously noted antigenic
      overlap of duck IgM and IgA. Messages for alpha and mu were detected in duck
      lymphoid organs but the alpha message was most abundant in the respiratory,
      alimentary and reproductive tracts. The alpha message first appeared around 14
      days of age and reached adult levels of expression only at 35-50 days. The
      results indicate that the duck has a mucosal immune system which utilizes IgA;
      however, the delayed expression and secretion of duck IgA explains the
      susceptibility of ducklings to mucosal pathogens. Since the waterfowl are among
      the most primitive extant birds, the recognition of IgA in the duck supports the
      conclusion that IgA occurs throughout the class Aves and also existed in the
      common ancestors of birds and mammals.

PMID- 9541603
TI  - Fibronectin-binding protein I of Streptococcus pyogenes is a promising adjuvant
      for antigens delivered by mucosal route.
AB  - A common problem in human vaccinology is the limited availability of efficient
      and non-toxic adjuvants capable of promoting mucosal responses. The potential
      usefulness of fibronectin-binding protein I (Sfbl) of Streptococcus pyogenes as
      immunological adjuvant was assessed using ovalbumin (OVA) as a model antigen.
      Mice were immunized by intranasal route, either with soluble OVA or OVA
      covalently coupled to Sfbl. Immunization with OVA-Sfbl resulted in the
      elicitation of about 100-fold higher titers of anti-OVA serum IgG than using OVA
      alone. The anti-OVA IgG subclass pattern was dominated in both groups of mice by
      IgG1, followed by IgG2b, IgG2a, and IgG3. Immunization with OVA-Sfbl also
      resulted in the elicitation of OVA-specific IgA in lung washes (24% of the total
      IgA), which was absent in mice immunized with OVA alone. Spleen cells from OVA
      Sfbl-immunized mice also gave a much stronger proliferative response to
      restimulation with soluble OVA in vitro. Phenotypic analysis of proliferating
      cells showed an enrichment in CD4+ T cells, producing a pattern of cytokines (IL
      4, IL-5, IL-6 and IL-10) characteristic of Th2-type cells. In contrast to
      immunization with soluble OVA alone, OVA-Sfbl induced the generation of CD8+ OVA
      specific cytotoxic cells. These results demonstrate that Sfbl represents a
      promising mucosal adjuvant able to substantially improve cellular, humoral and
      mucosal responses when coupled to an antigen administered by intranasal route.

PMID- 9541604
TI  - Involvement of the Fas (CD95) system in peripheral cell death and lymphoid organ
      development.
AB  - Fas-mediated apoptosis is a form of cell death that operates through a Fas-Fas
      ligand (FasL) interaction. In this study we investigated the role of the Fas
      system during development of normal and Fas-mutated lymphocytes. Irradiated RAG2
      /-recipients were reconstituted with bone marrow cells from B6 and lpr mice (Fas
      defective) or from B6 and gld mice (FasL defective), and analyzed for long-term
      development. The results showed a primary role of the Fas system in peripheral
      cell death and thymic colonization. In the periphery, the interaction in vivo
      between Fas+ and Fas-T cell populations indicated that cellular homeostasis was
      defective. Indeed, we observed a FasL-mediated cytotoxic effect on normal-derived
      T cells, explaining the dominance of lpr T cells in the mixed chimeras. The Fas
      mutation affected neither cell activation nor cell proliferation, as the effector
      (Fas-) and target (Fas+) cells behaved similarly with regard to activation marker
      expression and cell cycle status. However, Fas-T cells failed to seed the
      periphery and the thymus in the long term. We suggest that this could be due to
      the fact that FasL is involved in the structural organization of the lymphoid
      compartment.

PMID- 9541605
TI  - Modulation of amplitude and direction of in vivo immune responses by co
      administration of cytokine gene expression cassettes with DNA immunogens.
AB  - Immunization with nucleic acids has been shown to induce both antigen-specific
      cellular and humoral immune responses in vivo. We hypothesize that immunization
      with DNA could be enhanced by directing specific immune responses induced by the
      vaccine based on the differential correlates of protection known for a particular
      pathogen. Recently we and others reported that specific immune responses
      generated by DNA vaccine could be modulated by co-delivery of gene expression
      cassettes encoding for IL-12, granulocyte-macrophage colony-stimulating factor
      and the co-stimulatory molecule CD86. To further engineer the immune response in
      vivo, we investigated the induction and regulation of immune responses following
      the co-delivery of pro-inflammatory cytokine (IL-1 alpha, TNF-alpha, and TNF
      beta), Th1 cytokine (IL-2, IL-12, IL-15, and IL-18), and Th2 cytokine (IL-4, IL-5
      and IL-10) genes. We observed enhancement of antigen-specific humoral response
      with the co-delivery of Th2 cytokine genes IL-4, IL-5, and IL-10 as well as those
      of IL-2 and IL-18. A dramatic increase in antigen-specific T helper cell
      proliferation was seen with IL-2 and TNF-alpha gene co-injections. In addition,
      we observed a significant enhancement of the cytotoxic response with the co
      administration of TNF-alpha and IL-15 genes with HIV-1 DNA immunogens. These
      increases in CTL response were both MHC class I restricted and CD8+ T cell
      dependent. Together with earlier reports on the utility of co-immunizing using
      immunologically important molecules together with DNA immunogens, we demonstrate
      the potential of this strategy as an important tool for the development of more
      rationally designed vaccines.

PMID- 9541606
TI  - Genetic control of natural antibody repertoires: I. IgH, MHC and TCR beta loci.
AB  - Global analysis of natural antibody repertoires has revealed a marked
      conservation of reactivity patterns within inbred mouse strains, and
      characteristic strain-specific differences. We have now analyzed the genetic
      control of reactivity repertoires, aiming at identifying the respective selection
      mechanisms. Multiparametric statistics of a large number of serum antibody
      reactivities scored by quantitative Western blot analyses using extracts from
      homologous tissues and bacteria readily distinguish the reactivity patterns of
      C57BL/6 and BALB/c, revealing homogeneity among genetically identical
      individuals. Antibody repertoires in the prototype strains can also be segregated
      from those expressed by the respective IgH congenics, BC.8 and CB.20,
      demonstrating that IgH-linked genes contribute to determining natural antibody
      repertoires. Conversely, strains sharing IgH haplotype also express distinct
      reactivity patterns, indicating that other genes participate in the selection of
      serum IgM repertoires. Two such non-IgH loci were now identified. Thus, analysis
      of four MHC-congenic strains demonstrated that MHC-linked control of natural
      antibody repertoires is likely to operate through differential selection of T
      cell repertoires, since (1) mice that are congenic at the TCR beta locus, and (2)
      BALB/c nude mice grafted at birth with pure thymic epithelium from either C57BL/6
      or BALB/c also differ in their natural antibody repertoires.

PMID- 9541607
TI  - Amplification of tumor immunity by gene transfer of the co-stimulatory 4-1BB
      ligand: synergy with the CD28 co-stimulatory pathway.
AB  - We have explored the role of an activation-induced T cell molecule, 4-1BB
      (CDw137), in the amplification of tumor immunity by retrovirus-mediated
      transduction of the 4-1BB ligand (4-1BBL) into tumor cells. Mice inoculated with
      P815 tumor cells expressing 4-1BBL developed a strong cytotoxic T lymphocyte
      (CTL) response and long-term immunity against wild-type tumor. The optimal effect
      of 4-1BBL in CTL stimulation required B7-CD28 interaction since blockade of this
      interaction by antibodies down-regulated the expression of 4-1BB on T cells and
      decreased CTL activity. Furthermore, co-expression of 4-1BBL and B7-1 in the
      poorly immunogenic AG104A sarcoma enhanced the induction of effector CTL and the
      rejection of the wild-type tumor while neither 4-1BBL nor B7-1 single
      transfectants were effective, suggesting a synergistic effect between the 4-1BB
      and the CD28 co-stimulatory pathways. Our results underscore the importance of
      the 4-1BB T cell stimulation pathway in the amplification of an antitumor immune
      response.

PMID- 9541608
TI  - The hemagglutinin of recent measles virus isolates induces cell fusion in a
      marmoset cell line, but not in other CD46-positive human and monkey cell lines,
      when expressed together with the F protein.
AB  - Measles virus (MV) is efficiently isolated from patients with measles by using
      B95a cells, a marmoset B cell line. Recent wild-type MV strains isolated using
      B95a cells did not produce cytopathic effects in any of CD46+ primate cell lines
      examined (except B95a cells), nor did they induce downregulation of CD46.
      Transfection of the hemagglutinin (H) and fusion (F) genes of the Edmonston
      strain of MV produced syncytia in HeLa, Cos and B95a cells. By contrast, the
      expression of the H gene from the two wild-type strains, together with the F gene
      of the Edmonston strain, resulted in syncytium production in B95a cells, but not
      in HeLa and Cos cells. Cocultivation of Cos cells expressing the wild-type H
      protein and the Edmonston strain F protein with B95a cells, but not with HeLa,
      Jurkat or BJAB cells, generated large syncytia. The results suggest that these
      recent MV isolates may use a molecule other than CD46 as the cellular receptor or
      require another coreceptor to infect cells.

PMID- 9541609
TI  - pH-dependent aggregation and secretion of soluble monomeric influenza
      hemagglutinin.
AB  - We previously reported the expression of soluble A/Victoria/3/75 (H3N2)
      hemagglutinin in insect cells and the molecular and immunological structure of an
      aggregated fraction, only observed in cell supernatant when expression was
      performed at low pH [23]. Here we report that besides this aggregated a monomeric
      and possibly a trimeric structure is detected in cell supernatant, irrespective
      of the pH of the medium. Evidence is presented that the aggregated fraction is
      generated out of monomeric HAOs molecules due to a low intracellular pH
      encountered during secretion.

PMID- 9541610
TI  - Characterizations of natural and induced polyhedrin gene mutants of Bombyx mori
      cytoplasmic polyhedrosis viruses.
AB  - Bombyx mori cytoplasmic polyhedrosis virus (BmCPV) polyhedrin gene from natural
      mutant strain B, B2 and P was cloned and the amino acid sequence was compared
      with that of wild-type virus (strain H). Chimeric polyhedrin genes (8 types)
      containing only one site of mutation within the amino acid sequence were also
      constructed. Fifteen types of polyhedrin genes were introduced into a baculovirus
      expression vector and hexahedral, acicular, pyramidal, or amorphous polyhedra
      were formed in infected cells. These results demonstrated that the shape of
      polyhedra as well as the crystallization pattern of the polyhedrin could be
      changed by mutations at respectively N-terminal and C-terminal regions of BmCPV
      polyhedrin gene.

PMID- 9541611
TI  - Amplification of JC virus regulatory DNA sequences from cerebrospinal fluid:
      diagnostic value for progressive multifocal leukoencephalopathy.
AB  - Progressive multifocal leukoencephalopathy (PML) is a fatal demyelinating disease
      in the central nervous system caused by a ubiquitous human polyomavirus
      designated as JC virus (JCV). PML affects individuals with decreased immune
      competence and is now one of the common opportunistic infections in patients with
      AIDS. JCV DNAs in the brain of PML patients contain various PML-type regulatory
      regions that were generated from the archetypal regulatory region during
      persistence. Recently, many studies have suggested that detection of JCV DNA from
      the cerebrospinal fluid (CSF) may offer a tool for diagnosing PML. However, in
      all of these studies, coding sequences within the T antigen or capsid protein
      gene have been targeted for amplification. To amplify the JCV regulatory region,
      we established a nested PCR that could efficiently amplify the regulatory region
      from most JCV subtypes prevalent in the world. Using this PCR, we amplified JCV
      regulatory regions from the CSF samples from 4 patients strongly suspected of
      PML, whereas amplification was negative from 80 CSF samples from patients without
      PML. Sequencing of the amplified fragments revealed that they had unique
      deletions and/or duplications. Furthermore, in 3 PML patients, we analyzed the
      structures of regulatory regions derived from the brain as well as CSF. In each
      of these cases, the major regulatory sequence of both origins were identical.
      This finding indicates that JCV DNA in brain lesions is excreted in the CSF.
      Since the structures of PML-type JCV regulatory regions are unique to individual
      patients, the current PCR, if the amplified fragments are sequenced, can
      eliminate false positives that may arise from contaminations.

PMID- 9541613
TI  - Histographic recording of human immunodeficiency virus type 1 (HIV-1) regulatory
      protein Rev and nuclear factors.
AB  - HeLa cells and HeLa cells expressing the HIV-1 regulatory protein Rev were
      immunostained for Rev and pre-mRNA processing factors and examined
      histographically by confocal laser scanning microscopy. Following short pulse
      labelling with bromouridine tri-phosphate nascent RNA gave a granular
      nucleoplasmic staining increasing somewhat towards the periphery as did also the
      heterogeneous ribonucleoproteins (hnRNPs) A1 and particularly C1/C2, a
      distribution pattern which has not been described. The sm-antigen of the small
      ribonucleoprotein particle (snRNP) proteins U1, U2, U4/U6 and U5 stained the
      nucleoplasm diffusely in addition to speckles which co-localised with speckles of
      the non-snRNP splicing factor SC-35. Brominated RNA and the hnRNPs A1 and C1/C2
      were to varying degrees excluded from the speckles. Rev concentrated in the
      nucleolus and often as a perinucleolar ring/zone. Rev also stained the
      nucleoplasm and cytoplasm without co-localising with the above-mentioned proteins
      or brominated RNA and was not enriched or excluded in SC-35 speckles. The
      nucleolar proteins B23 and C23, like Rev, gave primarily a perinucleolar ring and
      stained the nucleoplasm but did not otherwise co-localise with Rev or with
      nuclear proteins. Histographic recording of immunofluorescence images proved to
      be a valuable tool in the study of localisation of HIV-1 Rev and cellular
      components and of possible co-localisations. A parallel comparison of the
      subcellular patterns of pre-mRNA processing factors versus major nucleolar
      antigens is new and suggests that the factors are not strictly separated in the
      nucleoplasm.

PMID- 9541612
TI  - Three forms of AU-1 like human rotaviruses differentiated by their overall
      genomic constellation and by the sequence of their VP8*.
AB  - Insight into the origin of human rotaviruses carrying the AU-1 VP4 allele was
      gained by examining their genomic RNA constellation using RNA-RNA hybridization
      and by sequencing the VP8* portion (nucleotides 1-750) of their gene 4. AU-1 like
      viruses isolated in Israel from children attending outpatient clinics were
      classified into three sub-genogroups based on RNA-RNA hybridization analysis:
      Subgenogroup 1 consists of two strains (Ro-5829 and Ro-5960) which belong to the
      AU-1 genogroup, since all their 11 segments hybridized to AU-1 segments.
      Subgenogroup 2 consists of one reassortant virus (Ro-5193) of which seven RNA
      segments hybridized to AU-1 segments and the remaining four segments hybridized
      to NCDV (bovine rotavirus). Subgenogroup 3 consists of four reassortant viruses
      (Ro-6460, Ro-6584, Ro-6784 and Ro-7044) which had a common genome constellation:
      only four of their RNA segments hybridized to AU-1 and the other seven segments
      hybridized to NCDV segments. Sequence analysis of the VP8* gene also revealed a
      three level pattern of homology with the AU-1 prototype and the local AU-1 like
      strains which was consistent with the overall genomic (RNA-RNA) constellation:
      Subgenogroup 1 had 98-98.1% homology with the AU-1 prototype; Subgenogroup 2 had
      96.8% homology with the AU-1 prototype and 95.6-96.7% homology with Subgenogroup
      1; Subgenogroup 3 had 95.3-95.6% homology with the prototype AU-1 and 93.4-94.3%
      homology with Subgenogroup 1. Possible evolutionary pathways are discussed.

PMID- 9541614
TI  - Further characterization of the latency-associated transcription unit of Marek's
      disease virus.
AB  - Previous studies have identified a large (L) and a small (S) RNA transcript
      antisense to the MDV homologue of the ICP4 gene of herpes simplex virus (HSV) in
      cells infected with Marek's disease virus (MDV) and in lymphoblastoid cell lines.
      In this study the 5' and 3' ends of the L RNA and of the sense ICP4 transcript of
      MDV were mapped by Northern hybridization and RNase protection assays. The
      results showed that L RNA is approximately 10.6 kb and that the ICP4 sense
      transcript is initiated in the region of genomic DNA where the L RNA terminates
      whereas L RNA is initiated where the ICP4 transcript terminates. L RNA was
      abundant in chick embryo fibroblasts (CEF) infected with virus strain
      HPRS16/attenuated whereas S RNA was predominant in CEF infected with oncogenic
      HPRS16 and in RPL-1 cell line. Results of cycloheximide experiments showed that
      the ICP4 gene of MDV was transcribed as an immediate-early gene in infected CEF
      whereas transcription of the L RNA required protein synthesis. Sequencing of cDNA
      and Northern hybridization using oligonucleotide probes showed that S RNA shared
      similar intron/exon boundaries as the cDNAs from several cell lines indicating
      that there might be a relationship between the S RNA and the antisense
      transcripts that generated the cDNAs.

PMID- 9541615
TI  - Identification of a conserved neutralization site in the first heptad repeat of
      the fusion protein of respiratory syncytial virus.
AB  - A large set of monoclonal antibodies (MAbs) directed against the fusion
      glycoprotein complex F1F2 of bovine respiratory syncytial virus (BRSV) and
      several polyclonal sera from infected or vaccinated animals were tested in
      Pepscan to locate linear epitopes on the F-protein. The polyclonal sera mapped to
      antigenic sites that correspond exactly to known antigenic sites on the F protein
      of human RSV. Only the neutralizing MAb 3 could be mapped with Pepscan. MAb 3
      reacted with three successive overlapping linear peptides that shared the amino
      acid sequence 173STNKAVVSLS182. The sequence of this novel neutralization site is
      conserved in all known BRSV- and human RSV-strains and is located on the N
      terminus of F1, adjacent to the hydrophobic, putative fusion-related region. This
      region is probably part of a central coiled-coil stem that is structurally
      conserved in paramyxovirus fusion and orthomyxovirus hemagglutinin glycoproteins.
      This linear conserved epitope may be a potential candidate for a peptide-based
      vaccine which can induce neutralizing antibodies against all groups and subgroups
      of RSV. Furthermore, the proposed structural features of the neutralization site
      may aid in the design of a peptide-based vaccine.

PMID- 9541616
TI  - Programmed cell death in the pathogenesis of rabbit hemorrhagic disease.
AB  - Rabbit hemorrhagic disease is a rapidly lethal infection caused by a calicivirus,
      characterized by acute liver damage and disseminated intravascular coagulation
      (DIC). Following morphological criteria and using a specific in situ labeling
      technique, we have found that liver cell death induced upon infection is due to
      apoptosis, and that programmed cell death is a constant feature in rabbits
      experimentally infected with RHDV. The process affected mainly hepatocytes, but
      also macrophages and endothelial cells presented morphologic hallmarks of
      apoptosis, expressing all these cell types viral antigens as determined by
      immunohistochemistry. The occurrence of programmed cell death was correlated with
      the appearance of the RHDV induced pathology in tissues by DNA fragmentation
      detection in situ. Hepatocyte apoptosis produced extensive parenchymal
      destruction causing a lethal, acute fulminant hepatitis that is characteristic of
      RHD. Apoptosis of intravascular monocytes and endothelial cell was observed
      together with fibrin thrombi in blood vessels. Since apoptotic cells are known
      sites of enhanced procoagulant activity, apoptosis of these cell populations
      might constitute a first step in the pathogenesis of DIC and a common pathway to
      other viral hemorrhagic fevers. In conclusion, apoptosis in RHD may be
      determinant in the development of the pathogenesis of this disease.

PMID- 9541617
TI  - Secondary structure prediction of the hemagglutinin-neuraminidase from a porcine
      rubulavirus.
AB  - The Hemagglutinin-Neuraminidase (HN) from 'La Piedad, Michoacan' porcine
      rubulavirus (LPMV) interacts specifically with NeuAc alpha 2,3 lactose residues
      on the target cell. In this work we report the secondary structure of this
      protein, determined with five different theoretical algorithms. Results indicate
      that the HN protein is organized in: an intracellular region (from amino acid 1
      to 25); in a beta-strand transmembrane region (residue 26 to 47), typically
      hydrophobic, rigid and solvent inaccessible; and extracellular region (48 to
      576), which possesses hemagglutinating and neuraminidase activity. The secondary
      structure in this region is organized in a beta-loop-beta alternated with few
      alpha-helices. Regions with structural and functional implications were
      determined by pattern search and multiple alignment of the HN from LPM with 12
      rubulaviruses and paramyxoviruses HN sequences. The low diversity observed among
      the HN sequences evaluated indicates that in general the structural organization
      of the protein, and in particular its sugar binding domain, is closely related
      among both genera, thus suggesting that the sugar binding domain is well
      preserved through evolution.

PMID- 9541618
TI  - Peanut yellow spot virus is a member of a new serogroup of Tospovirus genus based
      on small (S) RNA sequence and organization.
AB  - Peanut yellow spot virus (PYSV) represents a distinct tospovirus species based on
      serology and nucleic acid hybridization. THe sequence of the S RNA was 2970
      nucleotides with 22 nucleotide long inverted repeats (with three mismatches) at
      the termini. The coding was ambisense with a long open reading frame (ORF) in
      each strand. The 5'-large ORF (1,400 nucleotides in the viral sense (v) strand)
      encoded a protein with a predicted size of 53.2 kDa that was identified as the
      nonstructural (NSs) protein based on 16-21% sequence identity and 42-48% sequence
      similarity with other tospoviruses. A 3' ORF (741 nucleotides) in the virus
      complementary (vc) sense encoded a 28.0 kDa protein that was identified as the
      nucleocapsid (N) gene based on immuno-blot analysis of the in vitro expressed
      protein with PYSV polyclonal antiserum. The predicted N protein had 24-28% amino
      acid sequence identity and 44-51% sequence similarity with the members of other
      serogroups. In contrast to other tospoviruses, a third ORF (204 nucleotides)
      occurred in the vc strand, which could encode a protein with a predicted size of
      7.5 kDa with two strong hydrophobic regions. The low degree of homology of N and
      NSs protein sequences with other serogroup members coupled with an additional ORF
      suggests that PYSV should be classified as a distinct species of the Tospovirus
      genus. This conclusion also is supported by the absence of serological cross
      reaction with other serogroups, and biological characteristics including thrips
      transmission, symptoms and host range.

PMID- 9541619
TI  - Urine-associated horizontal transmission of Seoul virus among rats.
AB  - To understand the mode of transmission of Seoul type hantavirus in Wistar rats,
      we examined the shedding of the virus and antibody production in infected rats.
      When 1-day-old rats were inoculated with KI-83-262 strain of Seoul virus, the S
      segment of the viral genome was detected in lungs, clots, urine, saliva,
      submaxillary glands, rectums, and kidneys by nested reverse transcriptase PCR. On
      the other hand, when 8-week-old rats were infected with the virus, viral genome
      was detected only in the lungs and rectum. In uninfected newborn rats
      intranasally administered urine from infected newborn rats, four of six rats shed
      the virus into their urine. In addition, three of eight rats kept in same cage
      with infected animals also shed the virus into urine. Moreover, the virus genome
      was detected in the urine of urban rats (Rattus norvegicus) in an enzootic focus.
      These findings suggest that the urine containing virus from infected rats is an
      actual source of Seoul virus infection.

PMID- 9541620
TI  - Inhibition of hepatitis C virus adsorption to peripheral blood mononuclear cells
      by dextran sulfate.
AB  - Human peripheral blood mononuclear cells (PBMC) can be infected in vitro with
      sera of hepatitis C virus (HCV)-infected patients. We have treated pools of PBMC
      with dextran sulfate MW 8,000, before infection with various HCV(+) sera. When
      the cells were treated with dextran sulfate 10-3 M, HCV RNA was no longer
      detectable after infection with all HCV genotypes tested. When the cells
      incubated with dextran sulfate 10-3 M and 10-4 M were maintained in culture for 4
      weeks, no significant HCV replication could be observed. Our data suggest that
      dextran sulfate inhibits the attachment of HCV to the cell surface, since the HCV
      RNA detection was similar to control cells when dextran sulfate was added after
      infection.

PMID- 9541621
TI  - Moloney murine leukemia virus protease expressed in bacteria is enzymatically
      active.
AB  - Replication of Moloney murine leukemia virus requires a readthrough translation
      mechanism to generate the Gag-Pol polyprotein. One of the final products of this
      polyprotein is the protease (PR), which is required to generate the mature virion
      proteins. The assembly of Gag and Gag-Pol polyprotein into a virion followed by
      activation of the viral protease is necessary to produce a mature, infectious
      particle. These events are believed to occur near the cell membrane just prior to
      the budding of the virion. We report here the autoproteolytic activity of the
      viral PR when a Gag-PR fusion protein is expressed in E. coli. Efficient cleavage
      at the p12/CA, CA/NC and NC/PR junctions was observed. Thus the Moloney murine
      leukemia virus PR is capable of cleaving its substrates in the absence of
      specific host factors.

PMID- 9541622
TI  - Analysis of the B and T cell response in guinea pigs induced with recombinant
      vaccinia expressing foot-and-mouth disease virus structural proteins.
AB  - Recombinant vaccinia viruses expressing foot-and-mouth disease virus (FMDV) P1
      and VP1 genes have been used to study the immune response induced by these viral
      polypeptides in guinea pigs. Anti-FMDV antibodies, but not neutralizing activity,
      were detected in the sera from immunized animals. The results indicate that both
      CD4+ and CD8+ FMDV-specific T cells were induced by the vaccinia recombinants.
      Consistently with the activation of CD4+ T cells, lymphocytes from immunized
      animals specifically proliferated in vitro in response to whole virus. The
      induction of virus-specific CD8+ T cells was determined by CTL assay of immune
      splenocytes restimulated in vitro with FMDV infected cells. Altogether, the
      results obtained indicate that both B and T cell immune responses to FMDV are
      elicited upon immunization of guinea pigs with vaccinia recombinants expressing
      FMDV structural polypeptides.

PMID- 9541623
TI  - The replicative intermediate molecule of bovine viral diarrhoea virus contains
      multiple nascent strands.
AB  - The replication of bovine viral diarrhoea virus (BVDV) RNA is considered to
      involve replicative intermediates (RI) and replicative forms (RF) of virus RNA.
      These RNA species were radiolabelled metabolically by 3H-uridine in BVDV-infected
      cells and separated by sucrose gradient centrifugation. RNA in the fractions was
      then digested with RNase A in high salt (2 x SSC) and the RNase-resistance was
      determined. Using the Baltimore formula, this led to the calculation that the RI
      of BVDV contained 6-7 nascent strands on the template. This suggests that the
      structure of the BVDV RI is similar to that of poliovirus and dengue 2 virus.

PMID- 9541624
TI  - The nucleotide sequence of the coat protein genes of satsuma dwarf virus and
      naval orange infectious mottling virus.
AB  - The sequence of the 3'-terminal 4320 and 2409 nucleotides were determined for
      RNA2 of satsuma dwarf virus (SDV) and navel infectious mottling virus (NIMV).
      Both sequences contained a part of a long open reading frame which encodes larger
      and smaller coat proteins (CPs) at the 3'-terminus followed by a 3'non-coding
      region upstream of a poly (A) tail. Amino acid sequence identity for larger and
      smaller CPs ranged 81-84% and 68-78%, respectively, among SDV, NIMV and the
      previously sequenced citrus mosaic virus (CiMV). No significant sequence
      similarity was found between the CPs of SDV or NIMV and those of the como-, nepo-
      or other viruses. The nucleotide sequence identity of the 3' non-coding region of
      RNA2 were 68%-78% among SDV, CiMV and NIMV. These results suggest that SDV, CiMV
      and NIMV are distinct, though related, viruses. They may be assigned as members
      of the new genus, which is close to the genera of Comovirus and Nepovirus.

PMID- 9541626
TI  - A proposal for naming geminiviruses: a reply by the Geminiviridae Study Group
      Chair.

PMID- 9541625
TI  - Sequence analysis of the RNA polymerase gene of African horse sickness virus.
AB  - The gene encoding the inner core protein VP1 of African horse sickness virus
      (AHSV) serotype 9 has been cloned, expressed in vitro and entirely sequenced,
      completing molecular characterization of the AHSV genome. An analysis of the
      sequence supporting the identity of AHSV VP1 as the putative viral RNA polymerase
      is presented.

PMID- 9541627
TI  - Phase I trial of uracil-tegafur (UFT) plus oral leucovorin: 28-day schedule.
AB  - UFT [Taiho Pharmaceutical Co. Ltd., Tokyo, Japan; (BMS-200604), Bristol-Myers
      Squibb, Princeton, NJ], a fluorouracil prodrug, is an oral 4:1 molar
      concentration of uracil plus tegafur. This study examined the dose-limiting toxic
      effects and maximum tolerated dose of UFT plus leucovorin administered for 28
      consecutive days followed by a 7-day rest period. A course of therapy was
      repeated every 35 days. UFT dose levels examined were 200 mg/m2/day, with planned
      escalations to 250, 300, 350, and 400 mg/m2/day; the leucovorin dose remained at
      150 mg/day. Three patients were initially enrolled at each UFT dose level. The
      total daily doses of both UFT and leucovorin were divided into three doses
      administered every 8 hr. Diarrhea became the dose-limiting toxicity at 400
      mg/m2/day UFT, with grade 3 diarrhea noted in 2 of the 3 patients receiving that
      dose. To further define a phase II UFT starting dose, 3 additional patients were
      entered at the 350 mg/m2 level; 3 of the 6 patients treated at this level
      developed grade 3 nonhematological toxic effects. No partial or complete
      responses were observed. The recommended phase II UFT starting dose is 300
      mg/m2/day plus 150 mg/day leucovorin. Since neutropenia, significant mucositis,
      and "hand-foot syndrome" were not observed with UFT plus leucovorin, the toxicity
      profile of this regimen appears favorable compared with that of intravenous
      regimens of fluorouracil plus leucovorin. This phase I trial of UFT served as the
      basis for a phase II trial, current phase III trials, and a national adjuvant
      therapy trial of UFT for high-risk colon cancer patients.

PMID- 9541628
TI  - Circulating serum levels of cytokines and angiogenic factors in patients with
      cervical cancer.
AB  - Progression of cervical cancer is associated with excessive circulating levels of
      cytokines, which are known to be modulators of tumor angiogenesis. The
      concentrations of cytokines and growth factors were assayed using enzyme-linked
      immunosorbant assays in the serum of 61 women in various stages of cancer [stage
      0 (n = 6), stage I (n = 15), stage II (n = 15), stage III (n = 15), and stage IV
      (n = 10)] and of 20 healthy control subjects. Our results indicated that b-FGF
      and TNF-beta levels were significantly elevated in stage I, and serum levels of
      TGF-beta and IL-7 were elevated in stages II-IV of invasive carcinoma. Our
      experimental subjects had significantly increased serum levels of IL-6, GM-CSF,
      and angiogenin in stages I-IV of cervical cancer, and TNF-alpha serum levels were
      elevated in all stages of invasive carcinoma. The serum levels of IL-8 and IL-10
      were elevated only in stages II-III, and the levels of IL-2 were elevated in
      stages III-IV. The serum levels of IL-1 alpha and IL-1 beta remained unaltered in
      all stages of cancer progression. Progression of cervical cancer is associated
      with increased serum levels of angiogenin, IL-2, IL-6, IL-7, IL-8, IL-10, b-FGF
      TNF-alpha, TGF-beta, TNF-beta, and GM-CSF during different stages, all of which
      have the potential to be angiogenic amplifiers.

PMID- 9541629
TI  - Effect of ornithine in parenteral nutrition regimens on difluoromethylornithine
      induced platelet suppression and changes in tumor polyamine content.
AB  - We have demonstrated that DFMO-induced thrombocytopenia can be ameliorated with
      concomitant ornithine (Orn) in chow-fed rats; a reversal in DFMO-associated tumor
      polyamine reduction and antitumor activity, however, was also evident. To
      determine the effect of Orn in total parenteral nutrition (TPN) regimens on DFMO
      induced thrombocytopenia and changes in tumor polyamine concentrations, Ward
      colon-tumor-bearing (WCT) rats were given TPN with arginine (ENA) or with
      ornithine substituted for arginine (ENO) alone or with DFMO (1.5 g/day) added
      directly to the infusate. After 4 days, the peripheral blood platelet counts for
      ENA (917 +/- 151 x 10(3)/mm3) or ENO (908 +/- 67 x 10(3)/mm3) were equivalent to
      those of chow fed rats (901 +/- 42 x 10(3)/mm3). ENA/DFMO rats had significant
      thrombocytopenia (607 +/- 185 x 10(3)/mm3), which was completely ameliorated for
      ENO/DFMO rats (939 +/- 111 x 10(3)/mm3). Peripheral white blood count,
      hematocrit, and other hematological parameters were not affected. Tumor
      putrescine content for ENA rats (46.9 +/- 8.7 nmol/g) was equal to that for chow
      fed rats (44.8 +/- 6.2 nmol/g) and ENO rats (53.6 +/- 8.3 nmol/g). The reduction
      in tumor putrescine content for ENO/DFMO rats (19.6 +/- 6.9 nmol/g) was
      equivalent to that of ENA/DFMO rats (14.7 +/- 3.0 nmol/g). Tumor spermidine was
      reduced only for the ENA/DFMO rats while spermine was slightly elevated. Tumor
      spermine content for ENO/DFMO rats (57.2 +/- 12.0 nmol/g) was equal to that for
      ENO rats (65.6 +/- 8.7 nmol/g) but was significantly (p = 0.004) reduced when
      compared with rats receiving ENA/DFMO (89.4 +/- 20.4 nmol/g). The results of this
      study show that TPN with Orn substituted for arginine can be used with a
      chemotherapeutic dose of DFMO to ameliorate the thrombocytopenia. The DFMO
      induced reduction in tumor putrescine content, however, was not affected when Orn
      was substituted for arginine in a parenteral nutrition regimen. These results
      suggest that the antitumor activity of DFMO would not be adversely affected by
      coadministering DFMO with a TPN regimen with Orn substituted for arginine.

PMID- 9541630
TI  - Anticarcinogenic effects of shikaron, a preparation of eight Chinese herbs in
      mice treated with a carcinogen, N-butyl-N'-butanolnitrosoamine.
AB  - We studied the effects of Shikaron, which is composed of 8 Chinese herb extracts,
      on carcinogenesis and the cytotoxic activity and cytokine production of
      lymphocytes in mice treated with a carcinogen, N-butyl-N'-butanolnitrosoamine
      (BBN). We found a significantly lower incidence of urinary bladder carcinoma in
      mice treated with BBN plus Shikaron 200 mg/kg/day (5 of 20 mice, 25%), than in
      mice treated with BBN alone (16 of 20 mice, 80%). Shikaron protected the
      cytotoxic activity of lymphocytes against YAC-1 cells from suppression by BBN.
      Cytotoxic activity against P-815 cells significantly increased in mice treated
      with BBN plus Shikaron, as compared with normal mice and BBN-treated mice.
      Shikaron also protected production of interleukin-2 and interferon-gamma by
      lymphocytes from suppression by BBN. These findings strongly suggest that
      Shikaron exerted an anticarcinogenic effect in carcinogen-treated mice through
      activation of NK and LAK cells and cytokine production by T lymphocytes.

PMID- 9541631
TI  - Telomerase: putting an end to DNA.

PMID- 9541632
TI  - Cell adhesion molecules: an overview.
AB  - Considerable basic research, mostly in the past 20 years, has elicited greatly
      increased knowledge concerning the structure and function of cell adhesion
      molecules. Scores of individual adhesion molecules have been identified and
      categorized as to major structural features, ligands recognized, and pattern of
      expression. Recent attention has been focused on the interaction of cell adhesion
      molecules with intracellular components, and the role of cell adhesion molecules
      in mediating cell signal transduction. Ongoing efforts to develop specific
      pharmacological agonists and antagonists for adhesion molecules holds great
      promise in clinical medicine. Abciximab (Reopro), a monoclonal antibody inhibitor
      of the platelet integrin alpha IIb beta 3, is currently approved and available to
      improve vessel patency in patients undergoing angioplasty. Similar approaches to
      develop adhesion-based therapies to block angiogenesis, tumor progression, and/or
      metastasis are under development and hold promise for patients with cancer.

PMID- 9541633
TI  - Chromosomes in lymphomas and solid tumors.

PMID- 9541634
TI  - Cancer in the marital context: a review of the literature.

PMID- 9541635
TI  - Toward a new agenda for advocacy.

PMID- 9541636
TI  - Creatine kinase release after hepatic artery embolization in patients with
      carcinoid tumors.

PMID- 9541637
TI  - Human in vivo somatic mutation measured at two loci: individuals with stably
      elevated background erythrocyte glycophorin A (gpa) variant frequencies exhibit
      normal T-lymphocyte hprt mutant frequencies.
AB  - A survey of glycophorin A (gpa) in vivo somatic cell mutation in a population of
      394 healthy people from 8 to 77 years of age (mean age +/- SD 41 +/- 15 years)
      revealed a subset of 37 individuals with stably elevated allele-loss and/or
      allele-loss with duplication variant erythrocyte frequencies (Vf) exceeding 30 x
      10(-6). These 37 individuals with gpa outlier Vf are significantly older (P <
      0.001) than the remainder of the larger study population from which they were
      drawn reflecting a highly significant increase in the prevalence of these
      individuals in the population beyond age 40 years. A study of hpt mutant
      frequencies (Mf) in the peripheral blood T-lymphocytes of 27 of these
      individuals, together with 15 matched control individuals with unremarkable gpa
      Vf, was undertaken to determine if these subjects also displayed elevated
      mutation frequencies at this independent locus indicative of globally elevated
      somatic mutation. The hprt Mf in these 27 subjects (geometric mean 11.5 x 10(
      6)(dispersion interval 5.8 x 10(-6) to 22.8 x 10(-6)) was not significantly
      different from that observed in the 15 controls (geometric mean 12.1 x 10(
      6)(dispersion interval 5.7 x 10(-6) to 25.5 x 10(-6)). These Mf are higher than
      typically reported values reflecting the older age distribution of these
      individuals (arithmetic mean age +/- SD 53 +/- 12 and 50 +/- 16 years for the
      subjects and controls, respectively). Taken together, these data suggest that
      several genetic mechanisms may be responsible for producing the gpa outlier Vf
      observed in these subjects. The observation that hprt Mf were not increased
      indicates that the majority did not arise by a genome-wide increased rate of
      somatic mutation detectable at both loci. The fixation and subsequent expansion
      of 'jackpot' mutations at the gpa locus occurring early in embryonic/fetal
      development also does not appear to be a predominant mechanism. Some cases may
      result from a stable over-representation of gpa variant cells, perhaps associated
      with a marked age-dependent decrease in the number of contributing erythroid stem
      cells in the bone marrow. The subset that displays elevated allele-loss with
      duplication Vf involving both gpa alleles may represent individuals with
      increased rates of somatic recombination. Elevations arising by this mechanism
      are not detected in the hprt assay, but could be confirmed using a autosomal
      locus in vivo somatic cell mutation endpoint such as the hla-a assay. Of primary
      biological significance, these results demonstrate that genetics/stochastic
      processes leading to the loss of heterozygosity of somatic cells occur
      ubiquitously in humans and in some individuals this level of somatic mosaicism
      can approach a frequency of 10(-3) at the gpa locus in erythroid lineage cells.

PMID- 9541638
TI  - Molecular bases of hprt mutations in malathion-treated human T-lymphocytes.
AB  - Recently, we reported that 6 of 84 (7.1%) hprt mutants arising in in vitro
      malathion-treated human T-lymphocytes were characterized by specific genomic
      deletions in a 125-bp region of exon 3 (Pluth et al., Cancer Research 56 (1996)
      2393-2399. We have now extended study to determine whether additional differences
      in molecular spectrum at a basepair level exist between control and malathion
      treated mutations, and investigated whether there is evidence to support the
      hypothesis that malathion is an alkylating agent. We analyzed 101 hprt mutants
      (24 from control and 77 from treated cultures) isolated form six in vitro
      malathion exposures of T-lymphocytes from four healthy male donors. Analysis
      consisted of: Southern blotting, genomic multiplex PCR, genomic DNA sequencing
      and reverse transcription of PCR amplification (RT/PCR) and sequencing of the
      cDNA product. Mutations at several basepair sites were frequent after malathion
      exposure and were isolated from treated cells from at least two different
      individuals. Using a human hprt mutation database for comparison, the frequency
      of mutations at one of these sites (basepair 134) was found to be significantly
      elevated in the malathion-treated cell (p < 0.0005). Hprt mutations in malathion
      treated cells arose preferentially at G:C basepairs, which is consistent with
      earlier reports that malathion alkylates guanine nucleotides. Assessing molecular
      changes at both genomic and cDNA levels in the same mutants revealed that many
      small, partial exon deletions (< 20 bp) in genomic DNA were often represented in
      the cDNA at the loss of one or more exons. In addition, It was noted that
      identical genomic mutations can result in different cDNA products in different T
      cell isolates. These observations affirm the importance of genomic sequence
      analysis in combination with RT/PCR for a more accurate definition of the
      mutation spectrum.

PMID- 9541639
TI  - Protective effect of vanillin on radiation-induced micronuclei and chromosomal
      aberrations in V79 cells.
AB  - Vanillin (VA), an anticlastogen, has been demonstrated to inhibit gene mutations
      in both bacterial and mammalian cells. However, the data on its effect against
      radiation-induced cytogenetic damage are limited. The aim of this study was to
      investigate the protective effect of VA on radiation-induced chromosomal damage
      in V79 cells. Exponentially growing cells were exposed to five doses of X-rays (1
      12 Gy) and UV radiation (50-800 microJ x 10(2) cm-2 and posttreated with 3
      concentrations of VA (5, 50 or 100 micrograms ml-1 for 16 h for micronucleus (MN)
      and 18 h for structural chromosomal aberration (SCA) analyses. MN and SCA assays
      were performed concurrently according to standard procedures. Results indicate
      that there was a dose related increase in the percent of micronucleated
      binucleated cells (MNBN) (5.6 to 79.6) and percent of aberrant cells (Abs) (12 to
      98) with X-ray treatment alone. Inhibition studies showed that the addition of VA
      at 100 micrograms ml-1 significantly reduced the percent of MNBN (21 to 48)
      induced by X-ray at 1, 2, and 4 Gy. There was a slight decrease in percent MNBN
      at 5 and 50 micrograms VA ml-1. All three concentrations of VA decreased percent
      Abs (15.7 to 57.1) induced by X-rays at all doses. UV radiation alone
      significantly increased percent MNBN (3.5 to 14.8) and percent Abs (17 to 29).
      Addition of 50 or 100 micrograms VA ml-1, significantly decreased percent MNBN
      (31.7 to 86.2) and percent Abs (54.5 to 90.9) at all doses of UV radiation. A
      decrease in percent MNBN (2.8 to 72.4) and percent Abs (34.8 to 66.7) was also
      noted at 5 micrograms VA ml-1. These data clearly indicate the protective effect
      of VA on radiation-induced chromosomal damage, suggesting that VA is an
      anticlastogenic agent.

PMID- 9541640
TI  - DNA breakage by L-DOPA and Cu(II): breakage by melanin and bacteriophage
      inactivation.
AB  - We have previously shown that L-DOPA in the presence of Cu(II) caused DNA
      cleavage through the generation of reactive oxygen species such as the hydroxyl
      radical. Since L-DOPA is the precursor for the synthesis of melanin, we have
      studied the action of melanin on DNA in a similar reaction. In this paper, we
      show that melanin in the presence of Cu(II) also causes DNA strand breakage.
      However, the rate of such strand breakage is considerably less than l-DOPA.
      Melanin and L-DOPA are both capable of generating superoxide anion. Furthermore,
      the action of L-DOPA and Cu(II) on bacteriophage lambda reduces its viability.
      The results are discussed in relation to the putative role of L-DOPA-Cu(II)
      system as a source of endogenous generation of reactive oxygen species.

PMID- 9541641
TI  - Antimutagenic properties of probiotic bacteria and of organic acids.
AB  - Antimutagenic activities of live and killed cells of 6 strains of Lactobacillus
      acidophilus and 9 strains of bifidobacteria and of organic acids usually produced
      by these probiotic bacteria were determined using 8 potent chemical mutagens and
      promutagens. The mutagens and promutagens used were N-methyl, N'-nitro, N
      nitrosoguanidine; 2-nitroflourene; 4-nitro-O-phenylenediamine; 4-nitroquinoline-N
      oxide; Aflatoxin-B; 2-amino-3-methyl-3H-imidazoquinoline; 2-amino-1-methyl-6
      phenyl-imidazo (4,5-b) pyridine, and 2-amino-3-methyl-9H-pyrido (3,3-6) indole.
      The mutagenicity of these mutagens and antimutagenic activity of probiotic
      bacteria against the mutagens were determined according to the Ames TA-100 assay
      using a mutant of Salmonella typhimurium. Efficiency of bacterial cells in
      binding or inhibiting these mutagens was also investigated. Live cells of
      probiotic bacteria showed higher antimutagenic activity and their efficiency in
      inhibiting the mutagens was better than killed bacterial cells. Live bacterial
      cells bound or inhibited the mutagens permanently, whereas killed bacteria
      released mutagens upon extraction with dimethyl sulfoxide. Among the organic
      acids, butyric acid showed highest inhibition of mutagens followed by acetic
      acid. Lactic and pyruvic acids did not show appreciable levels of inhibition.

PMID- 9541642
TI  - Cadmium-induced alterations of hepatic lipid peroxidation, glutathione S
      transferase activity and reduced glutathione level and their possible correlation
      with chromosomal aberration in mice: a time course study.
AB  - Cadmium, a heavy metal, has been found to possess a potent toxic effect on liver
      and bone marrow. In the present study, attempts were made to understand whether
      or not any correlation existed between hepatic lipid peroxidation, glutathione S
      transferase activity, reduced glutathione level and chromosome aberrations,
      micronucleus and mitotic index in bone marrow cells of Balb/C male mice. Cadmium
      chloride (2.5 mg/kg b.wt.), when administered subcutaneously for 7 alternate
      days, exerted duration-dependent toxic effects on hepatic biochemical and
      cytogenetic parameters of bone marrow. A shorter time interval (5 days) elicited
      no significant alteration in the case of biochemical parameters, but with the
      advancement of time (i.e. after 10 and 15 days) lipid peroxidation showed 102% (p
      < 0.001) elevation and after 15 days, glutathione S-transferase activity and
      reduced glutathione level decreased by 35%, (p < 0.001) and 32% (p < 0.001),
      respectively, from the control values with concomitant elevation of chromosomal
      aberrations (30%) and micronucleus (2.32%) but the mitotic index was inhibited by
      1.26%. The results of our study, provided evidence of cadmium-induced duration
      dependent depression of GSH-mediated GST-catalysed detoxication capacity of the
      host and that this was presumably related to the induction of chromosomal
      aberrations. The clastogenic efficacy of this heavy metal was thus evident from
      the study.

PMID- 9541643
TI  - Superoxide formation and DNA damage induced by a fragrant furanone in the
      presence of copper(II).
AB  - 2,5-Dimethyl-4-hydroxy-3(2H)-furanone (2,5-DMHF), a caramel-like fragrant
      compound found in may processed foodstuff, has been reported to be mutagenic. 4,5
      Dimethyl-3-hydroxy-2(5H)-furanone (4,5-DMHF), which is a similar characteristic
      fragrant compound, has no report concerning its mutagenicity. DNA damage by 2,5
      DMHF and 4,5-DMHF was investigated by using DNA fragments obtained from the p53
      tumor suppressor gene. 2,5-DMHF induced DNA damage extensively in the presence of
      Cu(II), but only slightly in the presence of Fe(III). 4,5-DMHF did not cause
      metal-dependent DNA damage. Bathocuproine, a Cu(I)-specific chelator, and
      catalase inhibited DNA damage induced by 2,5-DMHF plus Cu(II), whereas free
      hydroxyl radical scavengers did not. The order of DNA cleavage sites was thymine,
      cytosine > guanine residues. The site-specific DNA damage and effects of
      scavengers show that DNA-copper-oxygen complex rather than free .OH are involved
      in the DNA damage. Formation of 8-oxodeoxyguanosine (8-oxodG) by 2,5-DMHF
      increased with its concentration in the presence of Cu(II), whereas 8-oxodG
      formation increased only slightly in the presence of Fe(III). Degradation of 2,5
      DMHF was efficiently accelerated by Cu(II), but only slightly accelerated by
      Fe(III). The degradation of 4,5-DMHF was little even in the presence of metal
      ions. Examination using cytochrome c suggest that superoxide was generated from
      2,5-DMHF. Stoichiometric study of Cu(II) reduction revealed that autoxidation of
      2,5-DMHF could offer 4-electron reduction. These results suggest that, at least
      in vitro and in an acellular system, 2,5-DMHF generates superoxide and
      subsequently hydrogen peroxide to induce metal-dependent DNA damage.

PMID- 9541644
TI  - Melatonin reduces gamma radiation-induced primary DNA damage in human blood
      lymphocytes.
AB  - Peripheral blood samples were collected from human volunteers 5-10 min before,
      and at 1 and 2 h after a single oral dose of 300 mg of melatonin. At each time
      point: (1) the concentration of melatonin in the serum and in the leukocytes was
      determined; and (2) the whole blood was exposed in vitro to 100 cGy of gamma
      radiation. Immediately after exposure to the radiation, the lymphocytes were
      examined to determine the extent of primary DNA damage, viz., single strand
      breaks and alkali labile lesions (determined from the length of DNA migration and
      fluorescence intensity of migrated DNA in the comet tail), using the alkaline
      comet assay. For each volunteer, the results showed a significant increase in the
      concentration of melatonin in the serum and in the leukocytes at 1 h after the
      oral dose of melatonin, as compared to the sample collected at 0 hour. The
      lymphocytes in the blood samples collected at 1 and 2 h after melatonin ingestion
      and exposed in vitro to 100 cGy gamma radiation exhibited a significant decrease
      in the extent of primary DNA damage, as compared with similarly irradiated
      lymphocytes from the blood sample collected before melatonin ingestion. The
      extent of the melatonin-associated decrease in primary DNA damage did not
      correspond with the decrease reported earlier in the incidence of chromosomal
      aberrations and micronuclei; the latter assays required an additional
      postirradiation incubation of the cells at 37 +/- 1 degrees C for 48 and 72 h,
      respectively.

PMID- 9541645
TI  - Induction of somatic intrachromosomal recombination inversion events by
      cyclophosphamide in a transgenic mouse model.
AB  - Somatic intrachromosomal recombination (SICR) can result in chromosomal inversion
      and deletion, mechanisms which are important in carcinogenesis. We have utilised
      a transgenic mouse model to study SICR inversion events in spleen cells. The
      transgenic construct is designed so that expression of an Escherichia coli lacZ
      transgene only occurs in a cell when an SICR inversion event occurs in the region
      of the transgene. The inversion events can then be detected by histochemical
      staining of frozen spleen sections for transgene expression and by polymerase
      chain reaction across the inversion breakpoints. The spontaneous inversion
      frequency in spleen rose 2-fold from 1.54 +/- 0.24 x 10(-4) (mean +/- SE) in 4
      month-old transgenic mice to 3.12 +/- 0.67 x 10(-4) in 22-month-old mice. Four-
      or 8-month-old mice were treated with a single intraperitoneal injection of
      cyclophosphamide, with doses ranging from 0.01 to 100 mg/kg. The animals were
      killed 3 days after treatment. A significant induction of SICR inversions was
      detected at all doses with a 3.2-fold maximum induction of inversions detected at
      10 mg/kg. These results suggest that the transgenic mouse model used here may be
      a sensitive model for studying the role of SICR in mutation and in studying risk
      assessment of environmental DNA-damaging agents.

PMID- 9541646
TI  - Inhibition of methotrexate-induced chromosomal damage by folinic acid in V79
      cells.
AB  - Methotrexate (MTX), an anticancer compound, is widely used in the treatment of
      leukemia. It induces cytogenetic damage as well as cytostatic effects on a
      variety of cell systems. Folinic acid (Leucovorin) is generally administered
      along with MTX as a rescue agent to decrease MTX-induced toxicity. However,
      information regarding the inhibitory effect of folinic acid against cytogenetic
      damage caused by MTX is limited. This study was conducted to assess the
      cytogenetic effect of MTX and its inhibition by folinic acid (FA) using the
      micronucleus and chromosomal aberration assays concurrently. Exponentially
      growing V79 cells were treated with MTX at five different concentrations (5-100
      micrograms ml-1) with S9 microsomal fraction for 6 h and post-treated with two
      concentrations of FA (5 or 50 micrograms) for 40 h. Results indicate that MTX
      alone induced a concentration-related increase in % micronucleated binucleated
      cells (MNBN) and % aberrant cells (Abs). There was a decrease in nuclear division
      index (NDI) with increase in MTX concentration. Similarly, the mitotic index (MI)
      also decreased in all concentrations of MTX tested. The addition of FA at 50
      micrograms ml-1 significantly reduced % MNBN (40-68%) and % Abs (36-77%).
      Inhibition was also seen at 5 micrograms FA (12 to 54% for MNBN and 20 to 61% for
      Abs). These results indicate that FA is capable of reducing the cytogenetic
      damage induced by MTX and appears to be an anticlastogenic agent.

PMID- 9541647
TI  - Intrachromosomal telomeric repeats and stabilization of truncated chromosomes in
      V79 Chinese hamster cells.
AB  - (TTAGGG)n sequences have been localized on the chromosomes of the Chinese hamster
      V79 cell line. A correlation between telomeric-like repeats and chromosome
      breakage has been found. Moreover, the analysis of the truncated chromosomes,
      typical of this cell line, has suggested that intrachromosomal (TTAGGG)n DNA may
      be important in the stabilization of the new telomeres.

PMID- 9541648
TI  - High frequency of sister chromatid exchanges in lymphocytes of the patients with
      Behcet's disease.
AB  - Behcet's disease (BD) (OMIM 109650) is an immunogenetically based multisystem
      disease, characterized by iridocyclitis, arthritis, orogenital ulcerations and
      pustular skin lesions. Viral and autoimmune etiologies have been suggested and
      HLA-B5 has been found to predominate in BD. The disease is most seen in Turkey
      and Japan. Although familial cases have been reported, the mode of inheritance is
      not clear. To determine the genetic instability in BD, sister chromatid exchange
      (SCE) analysis has been performed on peripheral lymphocytes in 23 patients and 20
      healthy controls. We found significantly higher SCE rates in the patient group (p
      < 0.0001). Our results may indicate that genetic impairment and genetic
      instability may play an important part in the etiology of BD.

PMID- 9541649
TI  - Fragile sites at the centromere of Chinese hamster chromosomes: a possible
      mechanism of chromosome loss.
AB  - On the basis of our previous observations showing that fragile sites (FS) mapped
      essentially in the centromeric regions of Chinese hamster chromosomes, we
      consider the possibility that the presence of FS at the centromere might be a
      source of chromosome loss. In this model a centromeric FS causes a centromeric
      break giving rise to two chromosome arms which could be lost or maintained with
      different consequences on the ploidy of daughter cells. To test this hypothesis,
      Chinese hamster cells have been treated both with N-methyl-N-nitrosourea (MNU), a
      mutagenic agent which also induces aneuploidy, and vinblastin (VBL), a pure
      aneugen, used as a control compound, which is supposed not to interact with DNA.
      The results show that MNU induces the formation of translocated and/or truncated
      chromosomes, on the contrary VBL is not able to induce chromosome rearrangements.
      The sites most involved in MNU-induced breaks are the centromeric regions of
      chromosomes where FS are also present. These breaks cause essentially the loss of
      one chromosome arm, so that the resulting cells are numerically diploid but
      presenting partial monosomies. The implications of these results are discussed.

PMID- 9541650
TI  - Unusual insertion element polymorphisms in the promoter and terminator regions of
      the mucAB-like genes of R471a and R446b.
AB  - We have previously identified umu-complementing genes on two incL/M plasmids,
      R471a and R446b (C. Ho et al., J. Bacteriol., 175 (1993) 5411-5419). Molecular
      analysis of these genes revealed that they are more structurally and functionally
      related to mucAB from the incN plasmid pKM101 than to other members of the
      previously identified Umu-like family. As a consequence, we have termed these new
      homologs mucAB(R471a) and mucAB(R446b) respectively. Interestingly, while the
      location of the mucAB-like genes is essentially the same in both R471a and R446b,
      the regions immediately flanking the mucAB-like genes are highly polymorphic. For
      example, 5' to mucAB(R471a) we found an insert that appears to be a novel
      retroelement encoding a putative reverse transcriptase (RT). This RT is related
      to the reverse transcriptases encoded by group II introns but is embedded in a
      retron-like context. Immediately 3' to the mucAB(R471a) locus is a putative
      insertion element of a sparsely-dispersed class not previously reported from
      enteric bacteria. Both the RT and insertion element are absent in R446b. These
      observations suggest that the mucAB-like genes from R471a and R446b are located
      within regions of the R-plasmids that perhaps were once (or still are) mobile
      genetic elements. Such observations might help explain the distribution of umu
      like genes on R-plasmids and bacterial chromosomes.

PMID- 9541651
TI  - Mutagenicity of 6-sulfooxymethylbenzo[a]pyrene in Salmonella typhimurium and
      Chinese hamster V79 cells.
AB  - 6-Sulfooxymethylbenzo[a]pyrene (SMBP) is an ultimate and reactive form of 6
      hydroxymethybenzo[a]pyrene (HMBP), which is converted into SMBP by the mediation
      of sulfotransferase. SMBP and HMBP with metabolic activation were mutagenic to S.
      typhimurium TA98 and TA100. The number of mutation per plate in strain TA98 was
      proportional to the concentrations of SMBP ranging from 0.2 to 1.0 nmol/plate,
      whereas that in strain TA100 was decreased at concentrations above 0.6
      nmol/plate. The mutation frequencies by HMBP was also increased in a dose
      dependent manner in both strains. Furthermore, SMBP and HMBP were highly
      mutagenic and cytotoxic to Chinese hamster lung fibroblast (V79) cells. A dose
      dependent increase in mutation frequencies at both hypoxanthine:guanine
      phosphoribosyltransferase (HGPRT) and sodium/potassium-ATPase (Na/K-ATPase) loci
      were found in V79 cells treated with SMBP and HMBP. The cytotoxicity of SMBP was
      increased with the increasing concentrations up to 2.5 microM, where the survival
      frequency and growth rate were decreased to almost 40% and 30% of the control
      value, respectively. The survival frequencies of V79 cells by HMBP were also
      decreased in a dose dependent manner up to 180 microM as similar to those of SMBP
      but the effects were less remarkable. SMBP was progressively accumulated in V79
      cells, reaching plateau in just 30 min. A dose dependent increase in complex
      formation with DNA or proteins was observed by treatment with SMBP. The
      mutagenicity and cytotoxicity of SMBP and HMBP may be derived from their binding
      capacity to DNA in V79 cells and S. typhimurium.

PMID- 9541652
TI  - Chloroform and carbon tetrachloride induce intrachromosomal recombination and
      oxidative free radicals in Saccharomyces cerevisiae.
AB  - Chlorination of drinking water results in the generation of low levels of
      numerous chlorinated hydrocarbons due to the reaction of chlorine with naturally
      occurring organic compounds in the water. Concern has been raised about the
      safety of these chlorinated contaminants as several of them, most notably
      chloroform (trichloromethane), have been shown to be carcinogenic in long-term
      rodent bioassays and weak correlations between trihalomethane levels in drinking
      water and an increased risk of bladder and colorectal cancer in humans have been
      found. Chloroform and carbon tetrachloride induce liver cancer in rats and mice
      only at doses where significant hepatotoxicity is observed and have been classed
      as non-genotoxic carcinogens. We have investigated the ability of chloroform,
      carbon tetrachloride and 1,1,1-trichloroethane to induce deletions via
      intrachromosomal recombination in the yeast Saccharomyces cerevisiae. Chloroform
      and carbon tetrachloride induced this genotoxic recombination event at similar
      doses, 1,1,1-Trichloroethane gave only a weak response in the DEL recombination
      assay and only at the highest dose. We further show that chloroform and carbon
      tetrachloride, but not trichloroethane, induced oxidative free radical species in
      our yeast strain. The free radical scavenger N-acetylcysteine reduced chloroform
      induced toxicity and recombination, and both chloroform and carbon tetrachloride
      were able to oxidize the free radical-sensitive reporter compound
      dichlorofluorescein diacetate in vivo. The implications of these findings to the
      carcinogenic activities of the three compounds are discussed.

PMID- 9541653
TI  - Induction of mosaic sex-linked recessive lethals in the different germ cell
      stages of Drosophila melanogaster by bleomycin.
AB  - The mutagenicity of bleomycin was studied in the different stages of
      spermatogenesis in Drosophila melanogaster. Following the injection of 2
      microliters of 0.1 micrograms/ml of the chemical into young wild-type males,
      complete and mosaic sex-linked recessive lethals were scored by the Muller-5
      method in five successive broods, mainly representing the different stages of
      spermatogenesis. The delayed mutagenic effect of the chemical was measured by the
      proportion of mosaic progeny produced. The results showed that bleomycin
      significantly increased the proportions of both complete and mosaic lethals in
      the broods representing the meiotic and pre-meiotic stages, but did not show any
      significant increase in these proportions in the broods representing the sperms
      and spermatids. The sizes of the mutated areas in the F1 gonads represented by
      the proportions of lethal-bearing females in F2 mosaic cultures were small,
      indicating that the genetic instabilities induced by bleomycin were transformed
      into actual mutations in later zygotic divisions. The significant divisions. The
      significant production of mosaic progeny in the F4 generation of the treated
      males showed that the mosaic F1 females produced by bleomycin were able to
      produce further mosaic progeny and suggested that bleomycin-induced instabilities
      can be transmitted as such for many future generations.

PMID- 9541654
TI  - The naevoid basal-cell carcinoma syndrome (Gorlin syndrome) is a chromosomal
      instability syndrome.
AB  - The Gorlin syndrome, or naevoid basal-cell carcinoma syndrome (NBCS) is an
      autosomal dominant cancer prone disease (at risk of multiple basal cell
      carcinomas, and other malignant or benign proliferations). We have previously
      reported data from peripheral blood lymphocytes of patients with this condition,
      showing a significant level of spontaneous chromatid and chromosome
      rearrangements and an overall lengthening of the cell cycle. In this paper, we
      confirm this disease to be a chromosome instability syndrome from studies on
      fibroblasts of 5 patients. Spontaneous chromosomal rearrangements, an increased
      frequency of sister chromatid exchanges and a slowing of the cell cycle were
      found, compared to age-matched control material. There was also an increased
      sensitivity to aberration production by mechlorethamine in patient fibroblasts.
      The chromosome instability we found was not restricted to a given cell lineage,
      but appears to be part of the general condition of this syndrome. The recently
      discovered gene responsible for Gorlin syndrome, PTC (or PTCH), encodes a
      transmembrane protein with yet poorly known functions. However, the demonstration
      of Gorlin syndrome as a chromosome instability syndrome suggests that this
      protein has a role in DNA maintenance, repair and/or replication.

PMID- 9541655
TI  - Synthesis, metabolism and structure-mutagenicity relationships of novel 4-nitro
      (imidazoles and pyrazoles) in Salmonella typhimurium.
AB  - A new series of 4-nitro-(imidazoles and pyrazoles) were synthesized as novel
      antimycotics and tested for their activation to mutagenic forms using Salmonella
      typhimurium TA98 and TA100, in the presence and in the absence of metabolic
      activation. TA100NR, TA100/1,8-DNP6, YG1026 and YG1029 strains were employed to
      identify a specific metabolic reaction which governs the mutagenic potency.
      Derivatives in the pyrazole group were generally found to be non mutagenic and
      active imidazoles were weak-direct-acting mutagens. For most of the compounds the
      mutagenic responses in TA98 were absent or 12- to 22-fold lower compared to
      TA100. The presence of a methyl or a benzylic group on the imidazole ring and
      substituents on the N1 and N3 positions were determinant for mutagenicity.
      Metabolism by bacterial enzyme systems was important to the expression of
      genotoxicity. Active compounds showed no mutagenicity toward the strain defective
      in classical nitroreductase and increased mutagenicity, from 2- to 7-fold
      depending on the test compound, toward the corresponding overproducing bacteria.
      On the other hand, compounds displayed reduced mutagenicity to the O
      acetyltransferase strain without having increased activity in the corresponding
      overproducing bacteria, YG1029.

PMID- 9541656
TI  - Enhancement of bone marrow radioprotection and reduction of WR-2721 toxicity by
      Ocimum sanctum.
AB  - The radioprotective effect of the leaf extract of Ocimum sanctum (OE) in
      combination with WR-2721 (WR) was investigated on mouse bone marrow. Adult Swiss
      mice were injected intraperitoneally (i.p.) with OE (10 mg/kg on 5 consecutive
      days), or 100-400 mg/kg WR (single dose) or combination of the two or double
      distilled water (DDW) and whole-body exposed to 4.5 Gy gamma-irradiation (RT).
      Metaphase plates were prepared from femur bone marrow on days 1, 2, 7 and 14 post
      treatment and chromosomal aberrations were scored. The maximum number of aberrant
      cells was observed at 24 h after irradiation in all the groups. However,
      pretreatment with OE or WR individually resulted in a significant decrease in
      aberrant cells as well as different types of aberrations. The combination of the
      two further enhanced this effect; resulting in a 2-fold increase in the
      protection factor (PF = 6.68) compared to 400 mg/kg WR alone. The percent
      aberrant cells decreased linear-quadratically with WR dose when given
      individually, while in the OE + WR pretreatment animals the values showed a
      linear dose response. Combination of OE with WR doses above 200 mg/kg completely
      eliminated rings, polyploidy and pulverization of chromosomes. Percent aberrant
      cells decreased with time in all groups, though the values remained higher than
      normal even on day 14 in the RT alone as well as those treated with single agent
      + RT. WR doses above 200 mg/kg before RT resulted in significantly higher
      frequency of aberrant cells compared to RT and OE + RT groups on day 14,
      suggesting delayed WR toxicity; but combination of OE with WR brought down these
      values to normal level, indicating that OE combination, in addition to enhancing
      WR protection, may also act as a detoxifier. The protective effect of OE and WR
      is also reflected in the enhancement of bone marrow CFU survival. Both OE and WR
      possessed significant free radical scavenging activity in vitro. The combination
      of the two further enhanced this effect, suggesting that the enhanced free
      radical scavenging activity by combining the two protectors results in the higher
      bone marrow cell protection. The significant elevation in chromosome protection
      obtained by combining OE with WR, with reduction in the latter's toxicity at
      higher doses, suggests that the combination may have promise for radioprotection
      in humans.

PMID- 9541657
TI  - Induction of forward mutations at the thymidine kinase locus of mouse lymphoma
      cells: evidence for electrophilic and non-electrophilic mechanisms.
AB  - A database of 209 chemicals tested for induction of forward mutations at the
      heterozygous thymidine kinase (TK +/-) locus in L5178Y mouse lymphoma cells was
      analyzed for structure-activity relationships using the MultiCASE expert system.
      Consistent with evidence of several contributing biological mechanisms, these
      studies suggest that such mutations may occur by more than one mechanism. As
      might be expected, there was evidence for a component involving direct
      electrophilic attack on the cellular DNA, in a manner previously established as
      causative in the induction of mutations in Salmonella. In addition, however,
      there was also strong evidence for another mechanism or mechanisms involving
      chromosome missegregation, cellular toxicity or an alternate site of action, such
      as the microtubules.

PMID- 9541658
TI  - Evaluation of mutant frequencies at the hprt and the T-cell receptor loci in
      pediatric cancer patients before treatment.
AB  - Mutant frequencies (Mfs) at the two genetic loci, the hypoxanthine phosphoribosyl
      transferase (hprt) gene and the T-cell receptor (TCR) gene were evaluated in
      pediatric cancer patients before starting chemotherapy or radiotherapy. The study
      population consisted of 27 patients with various solid tumors (mean age +/- SD;
      5.5 +/- 5.1 years, range; 0.2-14.5 years), 5 patients with acute leukemia (10.3
      +/- 6.1, 1.3-17.0 years), and 26 healthy controls (11.6 +/- 4.0, 4.4-22.2 years).
      Although the age distributions were different, the mean Mf values of the hprt and
      the TCR loci were comparable among these three groups. On an individual basis
      taking the age factor into consideration, the hprt-Mfs of 3 patients with solid
      tumors, i.e., two patients with Hodgkin's disease and one patient with Askin
      tumor, were found to be well above the 95% confidence limit. There were no
      patients with a TCR-Mf exceeding the 95% confidence limit. These data suggest the
      possibility that some patients with solid tumors may be predisposed to mutational
      susceptibility before treatment. The assay of the hprt-Mf appears more sensitive
      than the TCR-Mf assay in distinguishing these patients.

PMID- 9541659
TI  - Alteration of p53 protein in C3H/10T1/2 cells morphologically transformed by
      gamma-rays in stationary phase.
AB  - The panel of 70 transformed clones was isolated after exposure of C3H/10T1/2
      cells in stationary phase to low-moderate doses (1-4 Gy) of 137Cs gamma-rays. Two
      widely different dose rates were used: high (HDR, 0.66 Gy/min) and low (LDR, 4.8
      x 10(-4) Gy/min). Immunohistochemical analyses were performed by cellular
      staining with three types of monoclonal anti-p53 antibodies, Ab-1 (PAb421), Ab-3
      (PAb240) and Ab-4 (PAb246) in order to identify wild-type and altered
      conformation of the p53 protein in cell nuclei. The gamma-ray exposure led to
      induction of altered p53 protein in the majority of morphologically transformed
      clones. For LDR exposure the percentage of clones with changed p53 protein was 79
      (11/14), 71 (12/17) and 100 (6/6) for the exposure doses of 2, 3 and 3.6 Gy,
      respectively. For HDR exposure the percentage of such clones was 60 (3/5), 40
      (4/10) and 87 (13/15) for 1, 2 and 3 Gy, respectively. Moreover, in some
      transformed clones, especially in those induced by higher gamma-ray doses, p53
      protein in cell nuclei was not found. It was demonstrated by lack of the staining
      with Ab-1 antibody which can detect both mutant and wild-type of p53 protein. An
      altered conformation of p53 protein was detected, using Ab-3 antibody which does
      not react with its native conformation, in 27% (18/67) of all radiation-induced
      clones. A native conformation of p53 protein was recognized by Ab-4 antibody in
      33% (10/30) of clones induced by HDR, and in 22% (8/37) of clones induced by LDR
      exposure. Our study shows that alterations of p53 protein in cell nuclei is a
      frequent feature of morphological transformations induced by ionizing radiation
      in C3H/10T1/2 cells, and that these alterations occur independently of dose rate.

PMID- 9541660
TI  - Extent of DNA damage in density-separated trout erythrocytes assessed by the
      'comet' assay.
AB  - The 'comet' assay is being increasingly employed for evaluating DNA damage in
      biological systems. Using this technique, we examined DNA damage in whole in
      density-separated trout erythrocytes. Results clearly show that all the three
      considered parameters (tail length, tail intensity and tail moment) increased
      with the density of the fractions, possibly reflecting different degrees of DNA
      damage. Probably, this behaviour is due to different periods of exposure of the
      density fractions to the hazard of active oxygen radicals; older cells have been
      exposed to oxidative stress for a longer time.

PMID- 9541661
TI  - Prescribing in general practice. A review by the RCGP Prescribing Fellow in
      Scotland.

PMID- 9541662
TI  - [Injectionable valproate: experiences in neurology pediatrics and psychiatry.
      Workshop at Hamburg, 8 November 1997].

PMID- 9541663
TI  - [Pharmacotherapy of post-traumatic and postoperative pulmonary insufficiency.
      Substitution of natural surfactants].

PMID- 9541664
TI  - [Treatment of hypertension. Angiotensin blockade: an established therapeutic
      principle].

PMID- 9541665
TI  - [Elevated heart rate in the differential therapy with calcium antagonists].

PMID- 9541666
TI  - [Granisetron--anti-emetic therapy in current view].

PMID- 9541667
TI  - [Two new therapeutic principles in the management of breast cancer and colorectal
      cancer: selective oral aromatase inhibition and thymidilate synthase inhibition].

PMID- 9541668
TI  - [Therapy of endothelial dysfunction with ACE inhibitors].

PMID- 9541669
TI  - [KHK and treatment with calcium antagonists].

PMID- 9541670
TI  - [alpha-Interferon therapy in chronic hepatitis C evaluated].

PMID- 9541671
TI  - [Economic aspects of antibiotic therapy].

PMID- 9541672
TI  - [HIV therapy: concepts for today and tomorrow].

PMID- 9541673
TI  - [Experts take a position: Valproate--standard therapy in all forms of epilepsy].

PMID- 9541674
TI  - [Parkinson-therapy with dopamine agonists].

PMID- 9541675
TI  - [New analysis of CAPRIE (Clopidogrel vs Aspirin in Patients at Risk of Ischemic
      Events) shows: myocardial infarct most effectively prevented in the clopidogrel
      group].

PMID- 9541676
TI  - German oncology research shaken by fraud case.

PMID- 9541677
TI  - Prostate cancer: screening or watchful waiting?

PMID- 9541679
TI  - Recent advances in the molecular genetics of cancer. Second joint conference of
      the American Association of Cancer Research and the European Association of
      Cancer Research, Oxford, 9-12 September 1997.
AB  - The second joint conference of the AACR and the EACR held in Oxford from 9-12
      September 1997 was successful from many vantage points. While providing an
      optimal setting in which European and American cancer researchers could meet and
      exchange information, the conference had an excellent scientific programme which
      encompassed both methodological updates on important models used in cancer
      research and presentations of recent key advances in the molecular genetics of
      cancer. Lower eukaryotes are established model organisms used to elucidate
      fundamental but complex eukaryotic processes, such as those involved in
      tumorigenesis and cancer progression, and the progressive availability of their
      genome sequence makes them even more attractive. Transgenic mouse models are
      increasingly used not only for the study of one gene of interest but for
      investigation of the interactions among genes involved in the same pathway. The
      family of tumour suppressor genes is growing fast and several presentations were
      devoted to recently identified members such as the Von Hippel-Lindau gene, the
      FHIT gene and the PTEN gene. The systematic analysis of loss of heterozygosity on
      multiple loci in tumour specimens can provide the basis for preliminary models of
      molecular multistep progression in some tumour types, even though this is limited
      by the high degree of complexity found. Mechanisms of cell cycle regulation and
      apoptosis continue to be dissected and to constitute a fruitful area of
      investigation, with important recent insights on the p53-MDM2 autoregulatory loop
      and on the involvement of E2F-1 in apoptosis.

PMID- 9541678
TI  - Carboplatin versus cisplatin in solid tumors: an analysis of the literature.
AB  - BACKGROUND: Introduced into clinical usage in 1992 as a platinum analogue with a
      distinctively different toxicity profile from cisplatin, carboplatin has become a
      commonly preferred agent over cisplatin. The comparative therapeutic efficacy of
      the two agents remains controversial however, prompting an analysis of the phase
      III trials in ovarian cancer and other tumors in which the two were compared.
      METHODS: Clinical trials comparing carboplatin with cisplatin, both as single
      agents and in combination with other agents, were analyzed within the tumors for
      which platinum has become a standard or commonly employed agent. A Medline search
      identifying the randomized trials and references from these reports were collated
      for analysis. RESULTS: The original clinical comparative trials as well as
      literature reviews and commentaries were reviewed. Five solid tumors were
      identified within which comparative trials had been conducted: ovary, 10 trials;
      lung, 2 trials; head and neck, 2 trials; germ cell tumors, 3 trials and 1 trial
      in bladder cancer. Depending upon the end point selected, cisplatin was superior
      or equivalent to carboplatin in therapeutic efficacy in all five tumors but was
      associated with an increased toxicity profile for gastrointestinal, renal and
      neurologic effects. CONCLUSIONS: For some tumors, cisplatin appears to be
      superior to carboplatin in terms of therapeutic effectiveness (germ cell tumors,
      bladder cancer, head and neck cancer), while for others, effectiveness is
      comparable (lung cancer, ovarian cancer). Toxicity profiles are distinctly
      different for the two analogues however, generally favoring carboplatin. The
      issue of potential carboplatin underdosing related to the lack of physiologic
      dose calculations (utilizing the AUC [area under the curve] method) in the
      comparative trials of cis- versus carboplatin is probably not clinically
      important since a dose response effect has not been established for carboplatin
      or for cisplatin. The selection of the optimal platinum analogue to be employed
      is dependent on the type of tumor, the treatment intention (palliative vs.
      curative) and the other component drugs being used in combination.

PMID- 9541680
TI  - Incidence, mortality and survival from prostate cancer in Vaud and Neuchatel,
      Switzerland, 1974-1994.
AB  - BACKGROUND: Prostate cancer incidence has been increasing in most developed
      countries in the absence of similar trends in mortality, and with variable
      patterns in different areas of the world. MATERIALS AND METHODS: Trends in
      incidence and mortality from prostate cancer for the period 1974-1994 were
      analysed using data from the Cancer Registries of the Swiss Cantons of Vaud and
      Neuchatel. Of 5,010 cases registered, 80% were histologically or cytologically
      confirmed. RESULTS: Age-standardized incidence rates increased from 33.1 to 48.6
      per 100,000 (+47%). The upward trends were greater in the most recent calendar
      periods, and in the younger age groups (+77% at age 45 to 54; +57% at age 55 to
      64). In contrast, mortality was stable, with an overall increase of only 3% in
      age-standardized rates (from 20.4 to 21.0 per 100,000), due to some increase in
      men aged 65 or above. Consequently, the incidence/mortality rate ratios increased
      from 1.6 in 1974-1979 to 2.3 in 1990-1994. Five-year observed and relative
      survivals increased from 26% to 41% and from 46% to 58%, respectively. Ten-year
      observed and relative survival for cases diagnosed in 1985-1989 were 19% and 42%,
      respectively. Survival improvements were greater below age 75. CONCLUSION: The
      pattern of trends in incidence, mortality and survival confirms the influence of
      improved diagnosis of prostate cancer over the last few years in this European
      population. Still, while Swiss prostatic cancer mortality rates are the highest
      in the world (20.3 per 100,000, world standard), i.e., about 30% higher than in
      the United States, all races combined, incidence rates are still half as much. On
      account of the steady increase of prostate-specific antigen testing in
      Switzerland, further incidence increases are likely.

PMID- 9541681
TI  - Efficacy and safety of the paclitaxel and carboplatin combination in patients
      with previously treated advanced ovarian carcinoma. A multicenter GINECO (Group
      d'Investigateurs Nationaux pour l'Etude des Cancers Ovariens) phase II study.
AB  - BACKGROUND: Platinum compounds are the most active drugs in ovarian cancer
      treatment; cisplatin and carboplatin demonstrated similar efficacies but
      different toxicity profiles. Paclitaxel combined with cisplatin as first-line
      treatment improved overall survival when compared to a cisplatin-cyclophosphamide
      combination, but generated higher rates of neutropenia, febrile neutropenia and
      neurotoxicity. The paclitaxel-carboplatin combination may be better tolerated
      than cisplatin-paclitaxel. DESIGN: The objective of the present study was to
      assess the efficacy and safety of the combination of paclitaxel and carboplatin
      in previously treated advanced ovarian cancer patients. PATIENTS AND METHODS:
      During or after platinum-based chemotherapy, 73 patients with progressive
      advanced epithelial ovarian carcinoma were enrolled to receive every four weeks a
      three-hour infusion of paclitaxel 175 mg/m2 followed by a 30-minute carboplatin
      infusion. The carboplatin dose was calculated to obtain the recommended area
      concentration-versus-time under the curve of 5 mg x ml-1 x min. RESULTS: Toxicity
      and response could be evaluated for 72 and 62 patients, respectively. Eleven
      complete and 15 partial responses gave an overall response rate of 42% (95% CI:
      30%-54%). Response rates for platinum-refractory patients and those with early (>
      or = 3 and < 12 months) and late (> 12 months) relapses were 24%, 33% and 70%,
      respectively. The respective median response duration, the median progression
      free survival and median overall survival were 8, 6 and 14 months.
      Myelosuppression was the most frequent and severe toxicity. Grade 3 and 4
      neutropenia occurred, respectively in 30% and 23% of the cycles; 6% of the cycles
      benefited from medullary growth factors. Only one episode of febrile neutropenia
      was observed. Grade 3 and 4 thrombocytopenia occurred, respectively during 3% and
      1% of the cycles. Alopecia was frequent. Transient peripheral neuropathy
      developed in 47% of patients but was severe in only one patient. One early death
      was attributed to progressive disease and possibly to therapy. CONCLUSION: This
      combined paclitaxel-carboplatin therapy is effective and can be safely
      administered to ovarian cancer patients who relapse after one or two regimens of
      platinum-based chemotherapy.

PMID- 9541682
TI  - Paclitaxel in combination with weekly 24-hour infusional 5-fluorouracil plus
      leucovorin in the second-line treatment of metastatic breast cancer: results of a
      phase II study.
AB  - PURPOSE: To evaluate the antitumor activity in terms of response rate (RR), time
      to progression (TTP) and survival of paclitaxel in combination with weekly 24
      hour infusional 5-fluorouracil (5-FU)/leucovorin in pretreated metastatic breast
      cancer (MBC). PATIENTS AND METHODS: Fifty-four patients with bidimensionally
      measureable disease were included during phase II. Thirty-two had anthracycline
      resistant disease. Treatment consisted of 5-FU (24-hour i.v. infusion) 2.0 g/m2,
      leucovorin (two-hour i.v. infusion prior to 5-FU) 500 mg/m2, weekly for six weeks
      (day 1, 8, 15, 22, 29, 36) and paclitaxel (three-hour i.v. infusion) 175 mg/m2
      was administered additionally on days 1 and 22, q 50 days. RESULTS: We observed
      complete remissions in 4% of patients (2 of 54), partial remissions in 55% (30 of
      54), stable disease in 37% (20 of 54) and progressive disease in 4% (2 of 54).
      The overall RR was 59% (95% CI 48%-72%). The RR in 32 patients with anthracycline
      resistant disease was 59% (19 of 32). The median duration of response was 12
      months (3-22), median TTP eight months (2-22) and median survival time 15 months
      (2-28). Neutropenia was common, but of CTC grade 2 or 3 in most patients.
      Nonhematologic toxicities mostly consisted of CTC grade 1 and 2 myalgia,
      diarrhea, mucositis, nausea and vomiting. CONCLUSIONS: Paclitaxel combined with
      weekly 24-hour infusional 5-FU/leucovorin is well tolerated in the second line
      treatment of MBC. High efficacy was documented even in the treatment of
      anthracycline resistant disease, which warrants further evaluations.

PMID- 9541683
TI  - Selection and immunomagnetic purging of peripheral blood CD34+ cells for
      autologous transplantation in B-cell non-Hodgkin's lymphomas.
AB  - BACKGROUND: Clonogenic tumor cells in the hematopoietic progenitor cell harvest
      may contribute to relapse after high dose therapy for B-cell malignancies.
      Purging of the HPC harvest requires large amounts of anti-B-cell antibodies,
      whereas CD34-selection enriches self renewing HPC's but malignant cells are still
      detectable in many CD34+ fractions. PATIENTS AND METHODS: We examined the
      feasibility and safety of a CD34-selection followed by purging with anti B-cell
      antibodies in 11 patients with B-cell non-Hodgkin's lymphomas undergoing high
      dose therapy with cyclophosphamide, BCNU and etoposide with retransfusion of
      autologous HPC's. RESULTS: A mean number of 340 x 10(8) mononuclear cells was
      used for CD34-selection and immunomagnetic purging. CD34+ cells were enriched
      from a mean of 1.7% (range 0.2%-4.5%) to a mean of 68% (range 49%-87%) with a
      mean recovery of 27% (range 15%-43%). The mean number of retransfused CD34+ cells
      was 1.2 x 10(6)/kg (range 0.6-2.2 x 10(6)/kg) body weight with a median of 11
      days (range 10-13 days) to neutrophil recovery of 0.5 x 10(9)/l and 17 days
      (range 13-25 days) to platelet recovery of 50 x 10(9)/l. Mean number of
      intravenous antibodies and inpatient days were 8 (range 0-14) and 22 (range 19
      26) respectively. Major toxicity consisted in four septicemias. CONCLUSIONS: CD34
      selected and purged HPC's are safe and mediate rapid hematological recovery after
      high dose therapy for B-cell non-Hodgkin's lymphomas.

PMID- 9541684
TI  - Rearrangements of bcl-6, bcl-2, c-myc and 6q deletion in B-diffuse large-cell
      lymphoma: clinical relevance in 71 patients.
AB  - BACKGROUND: B-diffuse large-cell lymphomas (DLCL) have been associated with some
      molecular lesions, but the role of such lesions as prognostic markers is still
      controversial. This report concerns an investigation of the frequency and
      clinical correlation of bcl-6, bcl-2, c-myc rearrangements and 6(q) deletions in
      B-DLCL. PATIENTS AND METHODS: The presence of these genetic lesions was analyzed
      in samples of lymph nodes or bone marrow collected at diagnosis in 71 patients
      with B-DLCL, all treated with an anthracycline-containing chemotherapy regimen.
      RESULTS: Rearrangement of bcl-6 was found in 11 patients (15%), rearranged bcl-2
      in 12 (17%), 6(q) deletions in 10 patients (14%) and c-myc rearrangement in four
      (6%). Patients with rearranged bcl-6 tended to have a more aggressive disease
      than patients with germ-line bcl-6 (intermediate-high/high risk according to IPI
      criteria: 73% vs. 43%), but there were no differences in three-year survival
      rates (62% vs. 42%) between the two groups. The numbers of involved extranodal
      sites were similar in patients with rearranged and those with germ-line bcl-6.
      Patients with bcl-2 rearrangement appeared to have a less aggressive disease than
      those with germ-line bcl-2 (low/ low-intermediate risk 75% vs. 47%) and a
      slightly better three-year survival rate (70% vs. 41%) but again the difference
      was not significant. Both groups with or without 6(q) deletion had similar
      clinical characteristics and outcomes. The four patients with c-myc rearrangement
      had aggressive disease and did poorly. CONCLUSIONS: The analysis of molecular
      lesions in B-DLCL may be useful for a better diagnostic definition; however, in
      this study we were unable to show that the evaluated genetic lesions had a
      significant impact on clinical outcome.

PMID- 9541685
TI  - G-CSF prevents the suppression of bone marrow hematopoiesis induced by IL-12 and
      augments its antitumor activity in a melanoma model in mice.
AB  - BACKGROUND: IL-12 has been successfully used in experimental tumor therapy.
      However, administration of this cytokine induces dose-dependent suppression of
      hematopoiesis that could potentially limit its use in clinical trials. We decided
      to examine whether the myelosuppressive activity of IL-12 could be corrected by
      the administration of G-CSF. MATERIALS AND METHODS: In the initial experiments
      the influence of IL-12 and/or G-CSF on bone marrow and spleen GM-CFC was
      evaluated. To examine whether C-CSF could influence the antitumor activity of IL
      12 the combination therapy with these agents was carried out starting on day
      seven following inoculation of melanoma MmB16 cells into the footpads of B6D2F1
      mice. To obtain insight into the mechanism of the observed augmented antitumor
      activity of the combination therapy with IL-12 and G-CSF, the influence of these
      cytokines on macrophage activity (cytotoxicity and nitric oxide release) was
      analyzed. RESULTS: In accord with our expectations, the application of G-CSF
      partially prevented the suppression of bone marrow myelopoiesis in IL-12 treated
      mice. Unexpectedly, G-CSF also showed potentiation of antitumor effects of IL-12
      in this melanoma model. The augmented antitumor activity of combined IL-12/G-CSF
      immunotherapy could result from the enhanced stimulation of macrophage NO
      production and cytotoxicity. CONCLUSION: The simultaneous administration of IL-12
      and G-CSF partially prevented suppression of bone marrow myelopoiesis in IL-12
      treated mice. Moreover, treatment with these cytokines also results in
      potentiated antitumor effects in a murine melanoma model.

PMID- 9541687
TI  - Equianalgesic dose/ratio between methadone and other opioid agonists in cancer
      pain: comparison of two clinical experiences.
AB  - BACKGROUND: Oral methadone is considered to be a valid opioid analgesic
      alternative to morphine and hydromorphone in treating cancer pain. However, the
      use of methadone could be complicated by the limited knowledge of the
      equianalgesic dose/ratio with the other analgesic opioids when switching in
      tolerant patients. PATIENTS AND METHODS: In two Palliative Care Units, data
      collected regarding 88 advanced cancer patients with pain switched from different
      opioids to oral methadone were reviewed and compared with the aim of determining
      the equianalgesic dose ratio in relation to the dose of opioid previously
      administered. RESULTS: The results of this retrospective study suggest that: (1)
      methadone is much more potent than previously described in literature, (2) the
      dose ratio between hydromorphone and methadone is higher than as suggested by
      equianalgesic tables, and (3) the ratio correlates with total opioid dose
      administered before switching. CONCLUSIONS: The fact that methadone ratio is
      different according to the opioid dose used previously should be taken into
      careful consideration by the clinician in order to avoid severe toxicity or death
      during switchover. Prospective studies should be carried out in order to better
      define our findings.

PMID- 9541686
TI  - A phase I trial of human corticotropin-releasing factor (hCRF) in patients with
      peritumoral brain edema.
AB  - BACKGROUND: Human corticotropin-releasing factor (hCRF) is an endogenous peptide
      responsible for the secretion and synthesis of corticosteroids. In animal models
      of peritumoral brain edema, hCRF has significant anti-edematous action. This
      effect, which appears to be independent of the release of adrenal steroids,
      appears mediated by a direct effect on endothelial cells. We conducted a
      feasibility and phase I study with hCRF given by continuous infusion to patients
      with brain metastasis. PATIENTS AND METHODS: Peritumoral brain edema documented
      by MRI and the use of either no steroids or stable steroid doses for more than a
      week were required. MRIs were repeated at completion of infusion and estimations
      by dual echo-image sequence (Proton density and T2-weighted images) of the amount
      of peritumoral edema were performed. The study was performed in two stages. In
      the feasibility part, patients were randomized to receive either 0.66 or 1
      microgram/kg/h of hCRF or placebo over 24 hours. The second part was a dose
      finding study of hCRF over 72 hours at escalating doses. RESULTS: Seventeen
      patients were enrolled; only one was receiving steroids (stable doses) at study
      entrance; dose-limiting toxicity (hypotension) was observed at 4 micrograms/kg/h
      x 72 hours in two out of four patients, while zero of five patients treated at 2
      micrograms/kg/h developed dose-limiting toxicities. Flushing and hot flashes were
      also observed. Improvement of neurological symptoms and/or exam were seen in 10
      patients. Only small changes were detected by MRI. Improvement in symptoms did
      not correlate with changes in cortisol levels, and changes in cortisol levels
      were not correlated with changes in peritumoral edema. CONCLUSIONS: hCRF is well
      tolerated in doses up to 2 micrograms/kg/h by continuous infusion x 72 hours.
      Hypotension limits administration of higher doses. The observation of clinical
      benefit in the absence of corticosteroids suggests hCRF may be an alternative to
      steroids for the treatment of patients with peritumoral brain edema. Further
      exploration of this agent in efficacy studies is warranted.

PMID- 9541688
TI  - No evidence of significant activity of the multidrug resistance gene product in
      primary human breast cancer.
AB  - BACKGROUND: The discovery of the multidrug resistance (MDR1) gene product P
      glycoprotein (P-gp) has been widely seen as an important milestone in our
      understanding of the mechanisms underlying the clinical phenomenon of the
      emergence of resistant cells. MDR1 expression has been shown for numerous solid
      tumors and for virtually all hematologic malignancies. Nevertheless, results
      regarding MDR1/P-gp expression in human breast cancer have been controversial and
      the results of clinical trials on modulation of P-gp activity have not been
      encouraging. PATIENTS AND METHODS: MDR1/P-gp expression and the function of the P
      gp pump were investigated in 61 tumor samples from patients with primary breast
      cancers by multiparameter analysis using MDR1-RT-PCR, immunohistochemistry with
      two MAbs (UIC2 and MRK16) and the rhodamine 123 (Rh123) efflux assay. The
      cellular composition of the tumor cell suspension was analyzed by using specific
      MAbs against the P-gp expressing lymphocyte subsets CD4, CD8 and CD56, as well as
      against the HER-2/neu gene product, which was used to identify breast carcinoma
      cells. RESULTS: UIC2 and MRK16 revealed a staining positivity in 72% and 75% of
      samples, respectively. A positive MDR1-RT-PCR signal was detected in 62% of the
      samples. Nevertheless, no correlation between immunohistochemistry and RT-PCR
      could be established. Furthermore, there was no correlation between HER-2/neu
      expression and MDR1-RT-PCR or P-gp immunohistochemical assays. A contamination by
      CD8+ and CD4+ lymphocytes was established in 100% and 84% of tumor cell
      suspensions, respectively. As assessed by the Rh123 efflux assay CD8+ and the
      CD4+ lymphocytes exhibited marked P-glycoprotein activity, whereas such activity
      was not detectable in a single instance for the breast carcinoma cells. In MDR1
      RT-PCR positive samples, contamination by CD8 lymphocytes averaged 4.3%, while
      the contamination of CDS cells in the MDR1 mRNA-negative samples was only 2.4% (P
      = 0.007). This signal vanished after elimination of the lymphocyte subpopulations
      by T-cell rosetting. CONCLUSIONS: In primary breast cancer detection of MDR1 gene
      expression by means of RT-PCR or immunohistochemical assays is not indicative for
      the MDR phenotype, since there is no evidence of significant activity of the P-gp
      pump.

PMID- 9541689
TI  - Management of an isolated thymic mass after primary therapy for lymphoma.

PMID- 9541690
TI  - A phase I and pharmacologic study of DMP 840 administered by 24-hour infusion.
AB  - PURPOSE: DMP 840, a novel bisnaphthalimide, has demonstrated promising schedule
      dependent anti-tumor activity in vitro and in vivo against several tumor cell
      lines. A phase I study was conducted to evaluate the effect of a 24-hour infusion
      schedule repeated every three weeks, on the therapeutic efficacy of DMP 840.
      PATIENTS AND METHODS: Fourteen patients with refractory solid tumor malignancies
      were treated with DMP 840 at doses of 20, 40, 50 and 60 mg/m2. RESULTS: A
      combination of neutropenia, thrombocytopenia and stomatitis were dose-limiting at
      doses of 50 and 60 mg/m2 in both minimally- and extensively-pretreated patients.
      In contrast, all courses at lower dose levels were well tolerated.
      Pharmacokinetic analysis demonstrated that DMP 840 had a prolonged terminal half
      life (median 39 hours; range 25-86) and that dose-limiting events were
      significantly related to several indices of systemic DMP 840 exposure (P < 0.01,
      Wilcoxon Rank Sum test). CONCLUSION: The recommended dose of DMP 840 for further
      disease oriented evaluations is 40 mg/m2 administered over 24 hours every three
      weeks. The infusion duration evaluated in this study did not result in a
      substantial increase in the tolerable dose compared to shorter, less cumbersome
      schedules.

PMID- 9541691
TI  - Oxaliplatin as single agent in previously untreated colorectal carcinoma
      patients: a phase II multicentric study.
AB  - BACKGROUND: Oxaliplatin is a new cytotoxic agent from the diaminocyclohexane
      family with proven antitumor activity against colon cancer cell lines. Activity
      in patients with colorectal carcinoma previously treated with 5-fluorouracil has
      been studied in three single-agent phase II trials, showing a reproducible
      response rate of 10%. Here we report a phase II trial with oxaliplatin as a first
      line chemotherapy for metastatic colorectal cancer. PATIENTS AND METHODS: Twenty
      five patients were entered in the study. All of them had metastatic disease
      without previous chemotherapy, and at least one lesion had to be measurable by
      computed tomography (CT). Therapy consisted of a two-hour infusion of oxaliplatin
      at a dose of 130 mg/m2 every 21 days. RESULTS: The overall response rate
      determined by investigators was 20% (95% CI, 6.8%-40.7%). Eight patients (32%)
      had stable disease. The median time to disease progression in responders was six
      months (range four to nine). The median progression-free survival was four months
      and median overall survival 14.5 months (95% CI, 10-20 months). The main toxic
      effects were peripheral neuropathy (92%) and laryngopharyngeal dysesthesia (75%).
      No severe grade 3-4 neurotoxicities (NCI-CTC) were found. Gastrointestinal and
      hematological toxicities were mild. CONCLUSIONS: Oxaliplatin is an active agent
      in first-line chemotherapy for advanced colorectal cancer. It was well tolerated,
      caused no toxic deaths, had low hematotoxicity, well controlled gastrointestinal
      toxicity, and frequent but mild peripheral neurological symptoms. Therefore, it
      is of interest to associate oxaliplatin with other active compounds.

PMID- 9541692
TI  - CD44v6 is not a prognostic factor in primary breast cancer.
AB  - BACKGROUND: CD44 is an adhesion molecule and represents a highly variable family
      of isoforms. The isoform CD44v6 has been associated with metastasis formation and
      poor prognosis in animal models and human colon cancer. Results of studies in
      primary breast cancer are relatively small and contradictory. PATIENTS AND
      METHODS: The immunohistochemical expression of CD44v6 was studied in a series of
      338 patients with primary breast tumours, uniformly staged and treated in a
      single center with a long median follow-up of 128 months. The prognostic
      significance of CD44v6 as well as the correlation with several
      clinicopathological features were analysed. RESULTS: Two hundred nineteen of 338
      (64.8%) of the breast cancer were CD44v6-positive (> 5% of tumour cells with
      positive staining). CD44v6 expression had no value for prognosticating disease
      free or overall survival at this or any other cut-off point. CONCLUSION: CD44v6
      expression is not a prognostic factor in primary breast cancer.

PMID- 9541693
TI  - Detection of chromosome 3p alterations in serum DNA of non-small-cell lung cancer
      patients.
AB  - BACKGROUND: The generally dismal outcome of non-small-cell lung cancer (NSCLC) is
      believed to be associated with the systemic nature of this disease. In current
      practice, the decision to begin adjuvant chemotherapy in completely resected
      early stages is based on empirical criteria and has not yet been influenced by
      the presence of individual risk factors. Nonetheless, recent studies indicate
      that soluble tumor DNA is found in the serum and plasma of cancer patients, and
      microsatellite alterations have been identified in small-cell lung cancer and in
      head and neck neoplasms. PATIENTS AND METHODS: We have investigated serum DNA
      from 22 completely resected stage I-IIIA NSCLC patients using a polymerase chain
      reaction microsatellite analysis with four microsatellite markers at chromosome
      3p (D3S1038, D3S1611, D3S1067 and D3S1284). RESULTS: Our analyses showed serum
      tumor DNA in 6 of 22 (28%) cases, with microsatellite alterations, either as a
      shift (changes in the size of the microsatellite sequence in the autoradiograph)
      or as a loss of heterozygosity (LOH). LOH in both tumor and serum DNA at one or
      more microsatellite markers was found in four patients. Although it is still
      premature to look for prognostic implications, one patient with stage I serum DNA
      was identified prior to the development of distant metastases. CONCLUSIONS: The
      findings suggest that detection of free circulating DNA in sera of NSCLC patients
      is incidentally linked to the systemic nature of lung cancer even at the earliest
      stage. These observations provide the first hint that serum tumor DNA is present
      in NSCLC patients. The detection of DNA from cancer cells in the sera of NSCLC
      patients could be useful for monitoring relapse in a relatively non-invasive way,
      and the potential sensitivity of this test may help in selecting candidates for
      adjuvant chemotherapy.

PMID- 9541694
TI  - Prevention of hepatitis development by interferon-alpha in HBV carriers treated
      with intensive chemotherapy: a pilot study.

PMID- 9541695
TI  - Frey's syndrome after cisplatin-based chemotherapy for testicular teratoma.

PMID- 9541696
TI  - Tools for opportunity and professional presence.

PMID- 9541697
TI  - Rhizotomies.

PMID- 9541699
TI  - Laparoscopic paraesophageal hernia repair with Nissen fundoplication.
AB  - Laparoscopic approach to paraesophageal hernia repair is a recent application of
      minimally invasive videoscopic surgery. Procedures such as paraesophageal hernia
      repair with Nissen fundoplication that previously could only be performed as open
      techniques now can be performed laparoscopically. Laparoscopic approach of this
      major surgical repair benefits patients because of the reduced surgical time,
      decreased length of hospital stay, reduced hospital costs, and a reduction in
      loss of work time.

PMID- 9541700
TI  - Instrument design and cross-infection.
AB  - This article reviews recently reported patient-to-patient transmission of disease
      during endoscopic procedures and discusses several important instrument
      reprocessing issues. In addition, the author offers several infection control
      recommendations to minimize the risk of patient infection during endoscopic
      procedures.

PMID- 9541701
TI  - RN first assistants expand their perioperative role.
AB  - At the Cleveland Clinic Foundation, the RN first assistant (RNFA) role has
      expanded to include radial artery (RA) harvesting for coronary artery bypass
      surgery. This new role encompasses preoperatively assessing the RA with the
      Allen's test and perfusion index; intraoperatively removing the RA, dissecting
      the RA as a pedicle, and maintaining hemostasis and wound closure; and
      postoperatively collaborating with the postoperative muse clinician during
      patient care and management in the intensive care unit. This article outlines the
      RNFA's expanded role in this detailed surgical procedure.

PMID- 9541702
TI  - Ovarian masses in the pediatric patient.
AB  - Ovarian masses in the pediatric patient are uncommon. Children with ovarian
      tumors, however, pose diagnostic and therapeutic challenges because their
      presentation can mimic other more common intraabdominal disorders and their tumor
      histology varies widely. The refinement of surgical techniques and the advent of
      more effective chemotherapy in the past 25 years has increased overall survival
      rates from approximately 20% to 70%, thus improving the outcome for girls with
      malignant tumors. This article summarizes the current evaluation and management
      of ovarian masses in childhood and reviews pertinent pathology.

PMID- 9541703
TI  - Parliamentary procedure promotes order out of chao.

PMID- 9541705
TI  - Using a case scenario approach to evaluate age-specific competencies.
AB  - Age-specific competencies for staff members having direct patient contact is a
      requirement of the Joint Commission on Accreditation of Healthcare Organizations.
      This article addresses an annual competency evaluation of perioperative staff
      members relating to age-specific criteria. Several types of case scenarios were
      developed and given to staff members (eg, RNs, surgical technologists, OR
      assistants, postanesthesia care unit attendants) according to their specific job
      descriptions and responsibilities within the surgical services department. A case
      scenario format was used because of the variety of health care personnel and the
      ability to manipulate the scenarios according to the needs of patients, staff
      members, and the institution. The evaluation tools were meant to adequately
      assess staff members' abilities to care for patients throughout the life span.

PMID- 9541704
TI  - Implementation recommendations for making health care facilities latex safe.
AB  - The problem of latex allergy is not limited to health care workers who provide
      direct patient care. Individuals in environmental services, dietary, engineering,
      and medical records departments have the potential for sensitization. Due to the
      significant liability that may arise from a latex-induced anaphylaxis or death,
      it is no longer prudent for health care facilities to ignore the problem. This
      article proposes practical recommendations for implementation of an institution
      wide latex-safe environment in health care facilities.

PMID- 9541706
TI  - Health Care Financing Administration proposes to eliminate RNs from the OR.

PMID- 9541707
TI  - AORN response to Health Care Financing Administration proposal.

PMID- 9541708
TI  - Knowledge helps health care professionals deal with ethical dilemmas.

PMID- 9541709
TI  - The Dome offers health care providers, students, and community members a window
      to understanding.

PMID- 9541710
TI  - The first Reiki practitioner in our OR.

PMID- 9541711
TI  - Accessing health care literature--what every perioperative nurse needs to know.

PMID- 9541712
TI  - [Fatalities during imprisonment in Hamburg 1962-1995].
AB  - In this study, 275 fatalities in Hamburg's prisons from 1962 to 1995 have been
      evaluated retrospectively. 57% unnatural causes of death have been found. These
      included 120 suicides, 21 drug-related deaths and 6 homicides. Suicides are
      committed primarily by socially desintegrated prisoners with some experienced
      time of custody and the expectation of another, longer period of arrest. The
      preferred method is hanging. Mostly the motivation to suicide is due to the
      situation in prison as such. It cannot be stated that the staff had neglected the
      suicidal tendency of the imprisoned. Compared with other regions, the number of
      suicides lies in average bounds and remained constant over the years, with about
      138/100,000. The "Law of Imprisonment"/"Strafvollzugsgesetz" (1977) did not
      recognizably influence the number of suicides. Especially in the last years
      violent acts with succeeding death increased, but the absolute numbers are very
      low. Since 1989 a series of drug-related deaths occurred; among these there were
      no imprisoned being substituted with methadone up to 1995. Although one must
      regret every single case of death in prison, this study has shown in general that
      the circumstances in Hamburg have to be assessed by far less critical than it has
      been done occasionally with single cases in the public discussion.

PMID- 9541713
TI  - [Fatal poisoning with clozapine and perazine. A case report].
AB  - An intoxication following an apparent overdose of clozapine (Leponex) and
      perazine (Taxilan) is reported. There was a wide range of variation in postmortem
      blood and tissue concentrations of clozapine, desmethyclozapine and perazine.
      Clozapine/norclozapine blood and tissue ratios and perazine-pill-fragments in the
      gastric content could be used as a sign of suspected acute clozapine and perazine
      overdose.

PMID- 9541714
TI  - [Suicidal chloroform poisoning].
AB  - The results of the autopsy and of the toxicological analysis of a suicidal
      poisoning case by chloroform inhalation of a man (28) are described. The cause of
      death was acute cardiac failure, accompanied by centrolobular liver necroses.
      Quantitative analytical results (e.g. blood 47, liver 188, kidney 144, brain 74,
      urine 2 ug/ml, determined by head space GC were in agreement with literature
      data. The low concentration in stomach content indicated inhalation in accordance
      to the findings on site.

PMID- 9541715
TI  - [Methane in cadaver blood--homicide by natural gas or postmortem formation?].
AB  - A man had a quarrel with his wife. Suddenly he collapsed and became cyanotic. The
      woman supposed him to be dead. Because she was afraid of familiar requital, she
      opened the gas-cock of the cooking-range to pretend a suicide; methane emitted.
      The autopsy revealed a fresh cardiac infarction. Postmortem chemical analysis
      established methane in the blood. The question was, whether the methane had any
      importance for the death. By experimental inhalation of a methane-air-mixture
      (3%) we could expose, that the methane concentration in postmortem blood didn't
      have any relevance for the death.

PMID- 9541716
TI  - [Is identification of badly burned cadavers impossible? Reconstruction of the
      burned facial skull as a basis for roentgen identification].
AB  - The described case underlines all difficulties which arise in identification
      procedure of totally burned human remains. The main problem is the fragility of
      bone and tooth fragments and the radiological screening of structures of high
      individual specificity. After the fire in an old beekeeping a totally burned
      corpse has been found. The fragments of the bones and jaws were fixed with sodium
      silicate immediately. The viscero-cranium was reconstructed and x-rayed in an
      modified orthopantomography-x-ray-equipment. The comparison of pre- and
      postmortem radiographs made a positive identification possible.

PMID- 9541717
TI  - [An unusual injury pattern in magically increased false sex crime].
AB  - Case report on a rape-homicide by manual strangulation involving a 59 year old
      female. The autopsy disclosed a peculiar cross-shaped superficial incised wound
      of the abdomen, encircled by 12 stab-wounds, furthermore multiple superficial and
      deep incised wounds of the genitalia. The injury pattern was in good agreement
      with the psychiatric interpretation of the sexual behaviour as outlet of severe
      aggressive impulses originating from non-sexual motives.

PMID- 9541718
TI  - [Significance of a single tattoo in dyssocial probands. Statistical comparison of
      socially maladjustment, male delinquents with and without tattoos].
AB  - Although tattooing is not confined to the circle of sociopaths and delinquents,
      it is widely known, that criminal offenders always had heightened tendencies
      towards this kind of body ornamentation. The author makes an attempt to clarify
      the significance of a single tattoo in a sample of male delinquents by comparing
      the tattooed and the non-tattooed individuals. In spite of the popular prejudice,
      the results of this trial show, that delinquents with one tattoo stem from
      comparatively more favourable familiar backgrounds, are less loaded with mental
      disorders and delinquency among blood relatives, show better scholastic and
      professional accomplishments. However, tendencies toward addictive and delinquent
      behavior were comparable in the two groups.

PMID- 9541719
TI  - [The thiazolidinones--a new therapeutic agent for type 2 diabetes].
AB  - Both, impaired beta-cell function and insulin resistance, predominantly of the
      skeletal muscle, are considered to be the key factors in the pathogenesis of type
      2 diabetes (non-insulin-dependent diabetes; NIDDM). In the early stage of the
      disease, impaired insulin-mediated glucose disposal is accompanied by increased
      insulin secretion and hyperinsulinaemia. The thiazolidinediones (e.g.
      troglitazone), by improving insulin sensitivity of target tissues, appear to be a
      novel pathophysiologically interesting approach for the treatment of patients
      with NIDDM or impaired glucose tolerance. Troglitazone mainly elicits the
      following actions: Enhancement of insulin-mediated glucose disposal in patients
      with insulin resistance, impaired glucose tolerance and NIDDM, reduction of
      hyperglycaemia (blood glucose; HbA1c) and concomitant hyperinsulinaemia,
      improvement of dyslipidaemia in NIDDM. These actions are attained with
      monotherapy (200-600 mg once daily; plasma concentrations 0.3-3.0 micrograms/ml)
      or, with increased effects, when troglitazone is added to previously insufficient
      treatment with sulfonylureas or insulin. Potentially therapeutic actions with
      clinical relevance include (a) improvement of insulin resistance-associated
      hyperglycaemia-independent states of dyslipidaemia, (b) inhibition of LDL
      oxidation and (c) amelioration of function and/or protection of beta-cells, an
      effect indicating to a beneficial modulation of the second pathogenetic relevant
      factor of NIDDM. Troglitazone appears to be well tolerated by the majority of
      patients. Post-marketing reports of partly severe liver injury including deaths
      from liver failure among Japanese and U.S. patients taking troglitazone require a
      critical evaluation of the benefit to risk ratio of the drug and a careful
      monitoring of the patients.

PMID- 9541720
TI  - Variations of DNA damage in human lymphocytes after enflurane exposure in vitro.
AB  - The rate of DNA single strand-breaks in lymphocytes of 160 human donors were
      determined after enflurane (CAS 13838-16-9) exposure in vitro. The rate of DNA
      damage increased in relation to the exposed enflurane concentration. However, not
      every lymphocyte sample showed an increased rate of DNA damage; some samples
      showed an increased rate even after exposure to only 0.4 vol% enflurane and other
      samples showed no increased rate even after exposure to 4.0 vol% enflurane. After
      exposure to 0.6 vol% enflurane and more the increased rate of DNA damage is
      statistically significant. The DNA damage in the lymphocytes differs
      individually. The reasons may be genetic differences in DNA repair. In patients
      with DNA repair deficiencies anesthesia with enflurane may induce irreversible
      DNA damage.

PMID- 9541721
TI  - Pharmacological profile of nicardipine hydrochloride in anesthetized dogs with
      acute heart failure. Part 1: Hemodynamic effects in normal dogs and dogs with
      acute heart failure.
AB  - Cardiovascular effects of nicardipine hydrochloride (NIC, CAS 54527-84-3,
      Perdipine), a calcium channel blocker, were investigated in anesthetized normal
      dogs and dogs with acute heart failure (AHF), and compared with those of
      nitroglycerin (NTG). In open-chest anesthetized dogs, NIC (0.1-10
      micrograms/kg/min i.v.) dose-dependently increased cardiac output (CO) and
      coronary blood flow as well as decreased mean blood pressure (MBP). NIC had no
      effect on heart rate (HR) or maximum rate of rise of left ventricular pressure
      (max. dp/dt). In contrast (0.1-10 micrograms/kg/min i.v.) decreased MBP, but did
      not change the other cardiovascular parameters. NIC and NTG did not prolong PQ,
      QRS or QTc intervals. In addition, NIC was effective in the presence of
      dobutamine. In the anesthetized dog model of ischemic AHF induced by coronary
      ligation, and ischemia/angiotensin II-induced AHF, NIC (1 and 3 micrograms/kg/min
      i.v.) increased CO and stroke volume, and reduced total peripheral resistance
      without decreasing HR or cardiac contractility. Furthermore, in the
      ischemia/angiotension II-induced AHF model, NIC decreased left ventricular end
      diastolic pressure (LVEDP). In contrast, NTG (1-10 micrograms/kg/min i.v.)
      decreased LVEDP in both AHF models; but did not increase CO. These results
      suggest that NIC improves hemodynamics in dogs with AHF mainly by reducing
      afterload without adversely affecting the cardiac contractility or conduction
      system, while NTG exerts its effect on AHF by reducing preload. NIC injection
      would thus appear to be beneficial in the treatment of AHF.

PMID- 9541722
TI  - Pharmacological profile of nicardipine hydrochloride in anesthetized dogs with
      acute heart failure. Part 2: Effect on myocardial metabolism.
AB  - The effect of nicardipine hydrochloride (NIC, CAS 54527-84-3, Perdipine) on
      myocardial metabolism was investigated in an experimental model of ischemic acute
      heart failure (AHF) induced by coronary ligation in anesthetized dogs. The left
      anterior descending and/or circumflex coronary ligation decreased coronary sinus
      blood flow (CBF), maximum rate of rise of left ventricular pressure (max. dp/dt),
      cardiac output (CO) and stroke volume (SV), and increased left ventricular end
      diastolic pressure, indicating the development of AHF. In this ischemic AHF
      model, NIC (3 micrograms/kg/min i.v. infusion for 15 min) increased CBF, CO and
      SV, and reduced systemic and coronary artery resistances, resulting in the
      improvement of AHF. During the effective period, NIC decreased myocardial oxygen
      consumption and the coronary arterio-venous difference of oxygen content, carbon
      dioxide pressure and pH. At the same time, NIC did not decrease the lactate
      extraction. These results suggest that NIC improves hemodynamics and the balance
      of myocardium oxygen supply and demand in dogs with AHF by means of reducing
      afterload and dilating coronary artery.

PMID- 9541723
TI  - Enterohepatic recirculation of the new antihypertensive drug UP 269-6 in humans.
      A possible model to account for multiple plasma peaks.
AB  - Following a single dose of a new antihypertensive drug, UP 269-6 (5-methyl-7
      propyl-8-[(2'-(1H-tetrazol-5-yl) biphenyl-4-yl)methyl]-1,2,4-triazolo[1,5
      c]pyrimidin-2(3H)-one, CAS 148504-51-2), to 12 healthy volunteers, the plasma
      levels showed at least two secondary peaks. To explain this observation, the data
      were fitted to a new compartmental model of enterohepatic recirculation, without
      using a numerical method. Most subjects exhibited two cycles of recirculation.
      The amount of drug involved in each recirculation was calculated and the AUCs
      compared. The drug showed high biliary excretion and reabsorption.

PMID- 9541724
TI  - Effects of dihydrolipoic acid on peptide methionine sulfoxide reductase.
      Implications for antioxidant drugs.
AB  - By showing that dihydrolipoic acid (DHLA) reactivates oxidatively damaged alpha-1
      antiprotease (alpha 1-AP), a new antioxidant property of DHLA is described. For
      the first time, it is shown that a drug is able to reverse oxidative damage of
      physiologically essential macromolecules. Until now, only antioxidant properties
      have been reported that prevent oxidative stress. Repair of oxidized alpha 1-AP
      is catalysed by peptide methionine sulfoxide reductase (PMSR, EC 1.8.4.6). It is
      found that DHLA acts as a reducing cofactor for PMSR. Oxidized alpha 1-AP has
      been implicated in the etiology of certain lung diseases. Generally, by
      stimulating PMSR, DHLA may exert a curative effect in diseases accompanied by
      oxidative stress.

PMID- 9541725
TI  - Antitussive effect of azelastine hydrochloride in patients with bronchial asthma.
AB  - To investigate the efficacy of azelastine hydrochloride (azelastine, CAS 79307-93
      0, Azeptin) in suppressing cough, 22 bronchial asthma patients complaining mainly
      of cough were given the drug for four weeks. Peak flow rates (PEFR), pulmonary
      function tests, capsaicin cough threshold, and bronchial hyperresponsiveness were
      compared pre- and post-administration. After four-week's administration of
      azelastine (2 mg twice daily), cough decreased as demonstrated in a significant
      progressive improvement of cough points. The morning PEFR (1/min) was improved
      significantly at one week and two weeks post-administration. Changes were from
      434 +/- 26.4 pre-administration to 461 +/- 25.8 at Week 1 (p < 0.05), 462 +/-
      26.7 at Week 2 (p < 0.05), 452 +/- 22.5 at Week 3, and 462 +/- 20.8 at Week 4.
      The evening PEFR (1/min) showed 439 +/- 22.2 pre-administration, 454 +/- 21.4 at
      Week 1, 464 +/- 22.4 at Week 2, 457 +/- 19.3 at Week 3 and 467 +/- 17.8 at Week
      4, improvement being significant at Week 1 (p < 0.05). Regarding pulmonary
      function tests no significant changes were observed. FVC (liter), FEV1 (liter),
      and FEV1/FVC (%) were 3.45 +/- 0.86, 2.68 +/- 0.52, and 83.6 +/- 5.93 pre
      administration; and 3.48 +/- 0.21, 2.72 +/- 0.65, and 84.1 +/- 6.21 post
      administration, respectively. The capsaicin cough threshold [Ccap (mumol/l)]
      showed significant improvement, changing from 5.95 (0.016-50.0) pre
      administration to 19.7 (0.08-50.0) post-administration (p < 0.05). Conversely, an
      index of bronchial hyperresponsiveness, Dmin (mg/dl;U), showed no significant
      changes (14.9 +/- 5.2 vs. 19.7 +/- 5.3). These results suggest that azelastine
      inhibits cough in patients with bronchial asthma by increasing the level of the
      cough threshold without changing bronchial hyperresponsiveness.

PMID- 9541726
TI  - Lipid lowering effects of pravastatin in common marmosets.
AB  - In the present study it was examined if the common marmoset was susceptible to
      pravastatin (CAS 81131-70-6, CS 514, Mevalotin), an inhibitor of 3-hydroxy-3
      methylglutaryl coenzyme A (HMG-CoA) reductase. It has been reported that serum
      lipid levels in common marmosets resemble those in humans. First serum total
      cholesterol and lipoprotein cholesterol levels of common marmosets were examined
      in comparison with those in seven different experimental animals including
      cynomolgus monkeys, beagle dogs, Watanabe heritable hyperlipidemic rabbits,
      Japanese White Rabbits, Sprague Dawley rats, Wistar-Imamichi rats and golden
      hamsters. The animals were fed normal chow diets, and total- and lipoprotein
      cholesterol levels were determined under identical conditions. The quantitative
      and polyacrylamide electrophoresis studies indicated that among animals examined
      serum lipid and lipoprotein profiles in common marmosets were similar to those in
      humans. When pravastatin at 1-30 mg/kg was orally administered to common
      marmosets for 28 days, total, low density lipoprotein (LDL)- and high density
      lipoprotein-cholesterol levels were decreased in a dose dependent manner, whereas
      triglycerides and very low density lipoprotein cholesterol did not change. These
      findings confirm that common marmosets have serum lipid and lipoprotein profiles
      similar to those in humans suggesting that they are susceptible to lipid lowering
      effects of HMG-CoA reductase inhibitors.

PMID- 9541727
TI  - The role of magnesium in the generation and therapy of benign muscle cramps.
      Combined in-vivo/in-vitro studies on rat phrenic nerve-diaphragm preparations.
AB  - Rats received during 3 weeks a Mg-deficient or a Mg-rich diet; Mg-deficient
      animals revealed hypomagnesemia, cellular K-depletion and Ca-loading. Phrenic
      nerve-diaphragm preparations were studied; the physiological Tyrode solution
      contained low or high-Mg concentrations and 0 or 12 mmol lactate/L. Electric
      stimulation (indirect via the nerve or direct) produced tetanic contractions and
      increased force at increasing stimulation frequencies. Significantly lower
      frequencies were needed to elicit these effects when intra- and extracellular Mg
      levels were low, in comparison to plentiful Mg supply. Comparing unstimulated and
      stimulated diaphragmatic tissue electrolyte concentrations revealed tissue losses
      of Mg, K Ca from stimulated tissues which were less pronounced when Mg supply was
      optimal. These data support the empiric finding that relief from muscle cramps is
      promptly offered by Mg supplements.

PMID- 9541728
TI  - Synthesis of new thieno [2,3-d]pyrimidine-2,4(1H,3H)-diones with analgesic and
      anti-inflammatory activities.
AB  - A series of new 1,3-disubstituted thieno[1,3-d]pyrimidine-2,4(1H,3H)-diones were
      prepared to investigate their analgesic and anti-inflammatory properties. The
      analgesic and anti-inflammatory activities of synthesized compounds were
      investigated by the phenylquinone-induced writhing syndrome test, carrageenan rat
      paw oedema test and acetic acid-induced peritonitis assay. Most of the new
      compounds were found to be superior to mefenamic acid, as they were devoid of any
      ulcerogenic activity.

PMID- 9541729
TI  - Anti-inflammatory properties of mizolastine after oral administration on
      arachidonic acid-induced cutaneous reaction in the rat.
AB  - The anti-inflammatory effect of mizolastine (CAS 108612-45-9, SL85.0324-00), a
      new non-sedative histamine H1-receptor antagonist, was assessed in comparison to
      loratadine, terfenadine and pyrilamine. Intraplantar injection of arachidonic
      acid (AA) into the rat paw was followed by a rapid and sustained (> or = 4h)
      inflammatory oedema. Mizolastine (0.1 to 10 mg/ kg p.o.) inhibited in a dose
      dependent manner the time course of the AA-induced paw inflammation as from the
      dose of 0.1 mg/kg p.o. This effect was maintained for at least the 4 h of
      observation (-44% at 0.3 mg/kg p.o.) suggesting a long lasting action of
      mizolastine. Although with higher maximal effect, a similar time course of
      response was observed with dexamethasone at 0.1 mg/kg p.o. In contrast, at anti
      histamine, doses, the histamine H1-receptor antagonists terfenadine (1 to 30
      mg/kg p.o.), loratadine (10 mg/kg p.o.), and pyrilamine (10 mg/kg p.o.) failed to
      inhibit significantly the inflammatory action of AA. Moreover, under conditions
      of H1-receptors blockade (e.g. when co-administered with pyrilamine or loratadine
      (10 mg/kg p.o.), the inhibition by mizolastine (0.3 mg/kg) of AA-induced
      inflammation was unchanged. This suggests that the anti-inflammatory effect of
      mizolastine was unrelated to its histamine H1-receptor antagonist properties. It
      is proposed that a primary effect on the lipoxygenase pathway may contribute to
      this action of mizolastine. This is based on the observations that mizolastine
      inhibits 5-lipoxygenase activity in vitro. Furthermore, a high dose of
      mizolastine (50 mg/kg) did not affect the inflammatory response to carrageenin
      which is mediated by the cyclooxygenase pathway. Together, these data indicate
      that mizolastine is orally effective in this animal model for cutaneous
      inflammation. Combined with its blockade of histamine H1-receptors, this property
      may contribute to its possible use in allergic inflammation or other inflammatory
      states.

PMID- 9541730
TI  - Effect of mizolastine on visceral sensory afferent sensitivity and inflammation
      during experimental colitis.
AB  - In the present study the effect of mizolastine (CAS 108612-45-9, SL85.0324-00) a
      novel potent histamine H1-receptor antagonist, on 2,4,6-trinitrobenzene sulphonic
      acid (TNBS)-induced colitis, a rat model of inflammatory bowel disease, was
      investigated to determine whether mizolastine has anti-inflammatory properties.
      Treatment with TNBS resulted in increased nociception in response to rectal
      balloon distension and caused intestinal damage, tissue oedema and inflammation.
      Oral mizolastine (0.03-3.00 mg/kg given 1 h before and once daily for 3 days
      after TNBS treatment) significantly (p < 0.05) reduced nociception (49% at 0.3
      mg/kg), gross intestinal damage (78% at 3.0 mg/kg), histological damage (54% at
      3.0 mg/kg), intestinal tissue weight (69% at 3.0 mg/kg) and myeloperoxidase
      activity (66% at 3.0 mg/kg). In contrast, the H1-receptor antagonist terfenadine
      tested under the same experimental conditions at 3-30 mg/kg was without
      significant effect. It is concluded that, in addition to its antiallergic
      properties, mizolastine possesses anti-inflammatory actions that may not be
      related to its H1-receptor blocking properties, reducing sensory afferent
      hypersensitivity, damage and neutrophil infiltration observed during colitis.

PMID- 9541731
TI  - Effect of subinhibitory concentrations of some quinolones on a strain of Shigella
      dysenteriae type 1.
AB  - Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) revealed
      that the outer membrane proteins of a strain of Shigella dysenteriae exposed to
      four quinolone compounds (ciprofloxacin--CAS 85721-33-1, ofloxacin--CAS 83380-47
      6, pefloxacin--CAS 70458-95-6, and enoxacin--CAS 74011-58-8) at subinhibitory
      concentrations of 1/4 or 1/8 of the minimal inhibitory concentration (MIC) showed
      no alterations as compared to the control. Also the hydrophobicity of the cell
      surface of the test strain was not affected after exposure to subinhibitory
      concentrations of the quinolones.

PMID- 9541732
TI  - Antibacterial and sebosuppressive efficacy of a combination of chloramphenicol
      and pale sulfonated shale oil. Multicentre, randomized, vehicle-controlled,
      double-blind study on 91 acne patients with acne papulopustulosa (Plewig and
      Kligman's grade II-III).
AB  - In a 3-armed, multicentre, randomized, double-blind, vehicle-controlled study
      involving 91 patients with acne papulopustulosa, Plewig's grade II-III, evidence
      could be provided of a significant reduction of the propionibacteria as well as a
      subosuppressive effect (squalene reduction) under a combination of 1%
      chloramphenicol (CAS 56-75-7) and 0.5% pale sulfonated shale oil versus the
      alcoholic vehicle (1-2 ml twice daily). Likewise, monotherapy with
      chloramphenicol resulted in a significant reduction in bacteria compared to the
      vehicle. The combination therapy was superior to the monotherapy with regard to
      the sebosuppressive effects. Based on a kinetics test carried out for a total of
      2 h, a clinically relevant percutaneous absorption of chloramphenicol was ruled
      out. The chloramphenicol serum level was between < 5.0 microgram/l to 180
      microgram/l (average 25 micogram/l). This is important because with systemic
      application (peroral, i.v.), the therapeutic chloramphenicol level is > 25 mg/l
      (25,000 microgram 1). None of the blood count and serum parameters were
      pathologically changed in a clinically relevant way before and after the therapy.
      An induction of resistance against chloramphenicol in the propionibacteria could
      be excluded. No adverse events and side effects occurred. The topical therapy of
      acne papulopustulosa with chloramphenicol as a monosubstance or in combination
      with pale sulfonated shale oil represents an effective and safe local antibiotic
      treatment possibility.

PMID- 9541733
TI  - A new immunoenzymometric assay for bioactive N-terminal human parathyroid hormone
      fragments and its application in pharmacokinetic studies in dogs.
AB  - Advances in the treatment of clinical disorders of mineral in homeostatis and
      metabolic bone disease with intact parathyroid hormone 1-84 or one of the
      biologically active N-terminal fragments require a precise and sensitive
      measurement in serum. Therefore, a two-site immunoenzymometric assay for the
      quantitative determination of bioactive hPTH-1-37 (human parathyroid hormone) at
      picomolar concentrations was developed. Monoclonal antibodies (mAB) against hPTH
      1-37 were raised by hybridoma cells in serum-free cell culture. Furthermore,
      sequence-specific polyclonal antibodies were obtained by immunisation of rabbits
      using multiple antigenic peptides (MAP) representing the conspicuous regions of
      the primary structure of hPTH-1-37. The polyclonal and monoclonal antibodies were
      characterised by epitope mapping. The combination of a monoclonal antibody
      (13C63/5) recognising hPTH fragment 16-24 with a polyclonal antibody (k2) showing
      a predominant binding sequence at hPTH-1-5 led to a sandwich assay specific for N
      terminally intact and therefore biologically active hPTH. The validated assay
      ranging from 4 to 1000 pmol/l was applied to pharmacokinetic studies of hPTH-1
      37. After s.c. administration of 30 mu g/kg in 5 beagles, the maximum serum
      concentrations of hPTH-1-37 ranging at 2139 +/- 857 pmol/l were observed 45 min
      after the injection. Clearance of the peptide calculated from the exponential
      disappearance curve was 32.0 +/- 9.1 ml/min/kg with a mean t1/2 of 37 +/- 10 min.

PMID- 9541734
TI  - Alcohol-induced Purkinje cell loss depends on developmental timing of alcohol
      exposure and correlates with motor performance.
AB  - Several reports indicate that neonatal ethanol exposure induces cerebellar
      Purkinje and granule cell loss if exposure occurs before postnatal day (PD) 7,
      and that cerebellar damage may underlie ethanol-induced motor deficits. The
      present study used an unbiased stereological method, the optical fractionator, to
      count total cerebellar Purkinje cell number in groups of Sprague-Dawley rats
      given binge-like ethanol exposure at different neonatal ages. Correlations
      between Purkinje cell number (of 55-day-old rats) and parallel bar motor
      performance (previously tested on PD 30-32) were also evaluated. One group was
      given binge-like exposure to 6.6 g/kg per day of ethanol via artificial rearing
      on PD 4 and 5 (PD 4/5); a second group on PD 8 and 9 (PD 8/9); and a third group
      on both PD 4 and 5 and 8 and 9 (Comb). Gastrostomy (CG) and suckle (SC) control
      groups were also included. Purkinje cells were significantly reduced in all three
      ethanol-treated groups compared to controls, but the severity of loss was
      significantly greater in the PD 4/5 and Comb groups (reduced by 42% and 45%,
      respectively, relative to GC) compared to the PD 8/9 group (reduced by 15%).
      Across treatment groups, the total cerebellar Purkinje cell number was
      significantly correlated with successful parallel bar traversal (r = +0.74),
      supporting the contention that ethanol-induced motor deficits may be associated
      with cerebellar cell loss. These data confirm the presence of windows of
      vulnerability of Purkinje cells to neurotoxic effects of binge ethanol treatment,
      and demonstrate that both the behavioral and neuroanatomical consequences of
      binge exposure depend on the developmental timing of the exposure.

PMID- 9541735
TI  - Adenosine receptor-mediated inhibition of neurite outgrowth from cultured sensory
      neurons is via an A1 receptor and is reduced by nerve growth factor.
AB  - Adult dorsal root ganglion (DRG) cells are capable of neurite outgrowth in vitro
      as well as in vivo. We have investigated the influence of adenosine and analogs
      on the potential of cultured adult mouse DRG neurons to produce neurites in the
      presence and absence of nerve growth factor (NGF) which is a well-established
      trophic factor of sympathetic and sensory neurons during development. It is also
      believed to be essential for the maintenance or regulation of differentiated
      phenotypes of mature peripheral neurons. The results demonstrate that DRG neurons
      are modulated by purines in the absence of exogenous NGF. The addition of 100
      microM adenosine to neurite-bearing DRG neurons inhibited neurite growth by 47%
      after 2-day exposures in vitro and by 50% after 5 days whereas in the presence of
      NGF this inhibition was reduced to 28% and 32%, respectively. 100 microM CHA
      (N(6)-cyclohexyl adenosine) alone reduced neurite total length by 47% after 2
      days and by 48% after 5 days. 100 microM CGS21680 (2-p-(2-carboxyethyl)
      phenethylamino-5'-N-ethylcarboxamido adenosine hydrochloride) alone also reduced
      neurite total length by 46% after 2 days and by 58% after 5 days which was
      reduced to 21% and 37%, respectively, in the presence of 100 ng/ml NGF. The
      antagonist studies revealed that activation of A1 adenosine receptors is
      primarily responsible for the effect on neuritogenesis since the inclusion of 1
      or 10 microM CPX (8-cyclopentyl-1,3-dipropyl xanthine) fully prevented the
      inhibitory activity of adenosine or CHA whereas DMPX (3,7-dimethyl-1-propargyl
      xanthine) did not prevent inhibition by CHA. The converse experiment yielded the
      consistent result that inhibition by the A2 receptor agonist CGS21680 could be
      prevented by CPX, but not DMPX.

PMID- 9541736
TI  - The roles of mitotic arrest and protein synthesis in induction of apoptosis and
      differentiation in neuroblastoma cells in culture.
AB  - Studies of the response of neural crest tumor cells to the DNA cleaving
      antimitotic agent, neocarzinostatin, have left unanswered the question of whether
      the DNA cleavage per se or the antimitotic effect is responsible for this
      response. Furthermore, they do not define the timeframe within which a cell
      commits to its fate. Using the reversible microtubule-active agent, vinblastine,
      we now demonstrate that mitotic arrest, even without DNA cleavage, results in the
      same cellular changes as those seen with neocarzinostatin treatment. The
      commitment of the cell to its fate occurs within a 15 min treatment with
      vinblastine, and requires new protein synthesis. The immediate early gene
      products, c-Fos and c-Jun, appear not to be determinants of this process.

PMID- 9541737
TI  - Developmental expression of heme oxygenase-1 (HSP32) in rat brain: an
      immunocytochemical study.
AB  - Heme oxygenase (HO) is a microsomal enzyme that oxidatively cleaves heme
      molecules to produce bile pigments, iron and carbon monoxide. In normal adult rat
      brain, HO-2 is the most abundant isozyme whereas HO-1 is present at very low
      levels except in select cell populations. Because its promoter region has NF-kB
      and AP-1 sites, heat-shock and heme-responsive elements, the HO-1 isozyme can be
      induced by a variety of stimuli. Since the expression and activity of several
      transcription factors such as NF-kB, Fos/Jun, and CREB show specific changes
      during development, we postulated that HO-1 expression may show similar
      developmental regulation. Using immunocytochemistry and Western blotting, this
      study demonstrates the development changes of HO-1 protein expression in normal
      brain from rats at postnatal day 7 (P7), P14, P21, and adult. Brain HO-1
      immunoreactivity was highest at P7 in most brain regions including the white
      matter in areas of myelinogenesis, cerebral cortex, hippocampus, thalamus and
      hypothalamus and, in the blood vessel endothelial cells throughout the brain. In
      most regions, the adult pattern was reached by P21 with HO-1 protein localized
      almost exclusively to the dentate regions of hippocampus, some thalamic and
      hypothalamic nuclei, with little or no staining of endothelium, white matter and
      cortex. In a few select areas such as the substantia nigra, globus pallidus,
      ventromedial hypothalamic nucleus and the lateral preoptic nuclei area, little or
      no cellular HO-1 staining was observed at P7 whereas increased staining was found
      with maturation and adulthood. These results show that HO-1 protein expression is
      regulated in different cell types of specific regions of the rat brain during
      development.

PMID- 9541738
TI  - Afferent arrival and onset of functional activity in the trigeminothalamic
      pathway of the rat.
AB  - In this study, a novel in vitro slice preparation has been used to study the
      anatomical and physiological development of the trigeminothalamic pathway in the
      prenatal and neonatal rat. Anterograde tracing studies showed that the most
      rostral trigeminal fibres had reached the cephalic flexure by embryonic day
      (E)15, and entered the diencephalon by E16. By E17 the first few fibres had
      reached the ventroposteromedial thalamic nucleus (VPM) where they terminated in
      growth cones. The projection was more substantial and fibres had begun branching
      by E18, and arbors were more elaborate by E19. The fibres densely filled the
      nucleus by the day of birth (PO). The physiological studies showed that
      postsynaptic responses to stimulation of the trigeminal nerve or principal
      sensory nucleus (Pr5) could first be recorded at E17. Reliable responses to
      stimulation of either the nerve or Pr5 were recorded from E18 on. Stimulation of
      Pr5 enabled both axonal and synaptic signals to recorded in VPM. A GABAergic
      influence was acting to decrease the overall level of excitability in the
      thalamus from E18. In prenatal animals, the excitatory response was primarily
      mediated by NMDA receptors, and by P1 a non-NMDA mediated component was beginning
      to appear. These results demonstrate that the capacity for axonal conduction in
      the trigeminothalamic fibres and synaptic transmission in the thalamus are
      present from the time that anatomical connections are first established.

PMID- 9541739
TI  - Evidence for two populations of N-methyl-D-aspartate receptors in neonatal rat
      spinal cord. The effect of peripheral nerve axotomy.
AB  - Quantitative autoradiography was used to characterise the binding of the N-methyl
      D-aspartate (NMDA) receptor antagonist [3H]dizocilpine maleate (MK801) in the
      white matter and dorsal, intermediate and ventral subregions of the grey matter
      in the lumbar spinal cord of neonatal rats. The effect on the binding of
      unilateral sciatic nerve section on the day of birth was examined. In unoperated
      animals the Bmax and Kd of the binding had decreased in all subregions by two
      weeks, when the values were similar to those in the adult. After axotomy the Bmax
      values declined during the first 14 days in all subregions although the density
      appeared higher in the grey matter in the ventral horn compared to sham operated
      control. In the axotomised animals, the Kd values for the white matter and
      ventral horn grey matter had declined by two weeks but in the dorsal and
      intermediate subregions of the grey matter the values remained elevated. The
      results are consistent with the presence of two populations of NMDA receptor at
      birth. In the normal animals the lower affinity receptor disappears in all
      subregions, but after axotomy it is retained in the dorsal and intermediate
      subregions for at least 2 weeks.

PMID- 9541740
TI  - Muscimol-induced death of GABAergic neurons in rat brain aggregating cell
      cultures.
AB  - During brain development, spontaneous neuronal activity has been shown to play a
      crucial role in the maturation of neuronal circuitries. Activity-related signals
      may cause selective neuronal cell death and/or rearrangement of neuronal
      connectivity. To study the effects of sustained inhibitory activity on developing
      inhibitory (GABAergic) neurons, three-dimensional primary cell cultures of fetal
      rat telencephalon were used. In relatively immature cultures, muscimol (10
      microns), a GABAA receptor agonist, induced a transient increase in apoptotic
      cell death, as evidenced by a cycloheximide-sensitive increase of free
      nucleosomes and an increased frequency of DNA double strand breaks (TUNEL
      labeling). Furthermore, muscimol caused an irreversible reduction of glutamic
      acid decarboxylase activity, indicating a loss of GABAergic neurons. The muscimol
      induced death of GABAergic neurons was attenuated by the GABAA receptor blockers
      bicuculline (100 microns) and picrotoxin (100 microns), by depolarizing potassium
      concentrations (30 mM KCl) and by the L-type calcium channel activator BAY K8644
      (2 microns). As compared to the cholinergic marker (choline acetyltransferase
      activity), glutamic acid decarboxylase activity was significantly more affected
      by various agents known to inhibit neuronal activity, including tetrodotoxin (1
      micron), flunarizine (5 microns), MK 801 (50 microns) and propofol (40 microns).
      The present results suggest that the survival of a subpopulation of immature
      GABAergic neurons is dependent on sustained neuronal activity and that these
      neurons may undergo apoptotic cell death in response to GABAA autoreceptor
      activation.

PMID- 9541741
TI  - Ganglioside GM1 alters neuronal morphology by modulating the association of MAP2
      with microtubules and actin filaments.
AB  - In previous studies, we demonstrated that the exogenous ganglioside GM1 increased
      the complexity of the microtubular network and level of tubulin, selectively
      changed the distribution of microtubule associated protein-2 (MAP2)
      immunoreactivity from the perikarya to distal neuritic processes and increased
      immunogold label of MAP2 in the subplasmalemmal cytoplasm, neuritic filopodia and
      growth cones of Neuro-2a neuroblastoma cells. Since these areas are rich in actin
      filaments, our data suggested that MAP2 may be associated with microfilaments in
      the early stages of ganglioside-induced neuritogenesis. To determine if GM1
      alters neuronal morphology by facilitating the interaction of actin and MAP2, we
      examined the immunolocalization of these two proteins with confocal and electron
      microscopy. We found that along with the redistribution of MAP2 from perikaryal
      to neuritic regions, there was parallel redistribution of actin. The uniform
      subplasmalemmal actin meshwork was disrupted in areas of processes and filopodia
      with a redistribution of actin to these areas in close association with MAP2. Our
      present results suggest that gangliosides enhance neuritogenesis by
      redistributing actin as well as MAP2 to processes and filopodia thereby
      facilitating their interaction. The association of MAP2 with actin filaments is
      likely to be an early step in ganglioside-mediated filopodia formation.

PMID- 9541742
TI  - A comparative study of ethanol, hypoglycemia, hypoxia and neurotrophic factor
      interactions with fetal rat hippocampal neurons: a multi-factor in vitro model
      developmental ethanol effects.
AB  - Fetal alcohol syndrome (FAS) is characterized by numerous central nervous system
      anomalies, with the hippocampus being particularly vulnerable to developmental
      ethanol exposure. In addition to direct ethanol neurotoxicity, other conditions
      resulting from maternal ethanol consumption, such as hypoglycemia and hypoxia,
      may also contribute to FAS. The present study used a tissue culture system to
      model multiple conditions which may relate to in vivo FAS, and assessed their
      relative neurotoxicity with MTT assays. Gestational day 18 rat hippocampal
      cultures were exposed to varying ethanol concentrations, glucose withdrawal
      induced hypoglycemic (gwHG, 16 h) or acute hypoxic (aHP, 2 h) conditions alone,
      as well as to co-treatments with ethanol and gwHG or aHP. Brain-derived
      neurotrophic factor (BDNF) and nerve growth factor (NGF) have previously been
      shown to ameliorate ethanol-, hypoglycemia- and hypoxia-induced neurotoxicity.
      Therefore, their neuroprotective potential, along with ciliary neurotrophic
      factor (CNTF), was examined. Neuronal viability was reduced dose-dependently by
      ethanol, alone or with hypoglycemia or hypoxia. Ethanol + gwHG or aHP was not
      uniformly additive. NGF treatment provided the most extensive neuroprotection,
      being effective against ethanol (200 and 400 mg/dl), gwHG, and aHP, alone and
      combined. BDNF afforded similar protection, but not against ethanol + gwHG. CNTF
      protected only against aHP. CNTF + BDNF, previously shown to act synergistically,
      protected against ethanol + aHP up to 800 mg/dl ethanol, but not, paradoxically,
      against ethanol alone, gwHG, or ethanol + gwHG, all conditions BDNF alone
      protected against. This study demonstrated that several neurotrophic factors are
      capable of mitigating neurotoxicity associated with ethanol, hypoglycemia and
      hypoxia.

PMID- 9541743
TI  - Ontogenic expression of natriuretic peptide mRNAs in postnatal rat brain:
      implications for development?
AB  - The central natriuretic peptide system is composed of at least three structurally
      homologous and uniquely distributed peptides and receptors which are thought to
      be involved in the central regulation of cardiovascular and autonomic function
      and more recently been shown to affect cellular growth and proliferation,
      processes pertinent to mammalian development. As such, following our initial
      mapping of preproatrial natriuretic peptide (ppANP) mRNA in adult brain [M.C.
      Ryan, A.L. Gundlach, Anatomical localization of preproatrial natriuretic peptide
      mRNA in the rat brain by in situ hybridization histochemistry: in olfactory
      regions, J. Comp. Neurol., 356 (1995) 168-182], it was of interest to determine
      the ontogenic expression of natriuretic peptide mRNAs in the developing rat
      brain. Using in situ hybridization histochemistry of specific [35S]- or [33P]
      labeled oligonucleotides, ppANP and preproC-type natriuretic peptide (ppCNP)
      mRNAs were detected in the developing rat brain from postnatal day 4 to day 60
      (adult). PpANP mRNA was observed in many hindbrain, but only some forebrain,
      regions at postnatal day 4. Regional differences in the temporal expression of
      ppANP mRNA were apparent with ppANP mRNA detected in the medial preoptic area,
      mammillary nuclei and medial habenular nucleus at postnatal day 4 and in other
      areas including the arcuate and dorsomedial hypothalamic nuclei and in olfactory
      and limbic regions at postnatal day 10. A number of regions also exhibited
      transient expression of ppANP mRNA such as the bed nucleus of the stria
      terminalis and the medial cerebellar nucleus. In contrast, ppCNP mRNA was
      detected at relatively high levels in several regions on postnatal day 4
      including olfactory nuclei, the hippocampus and particularly the pontine nucleus.
      The level of expression appeared to increase markedly in most regions including
      forebrain olfactory and hippocampal areas and in brainstem regions including the
      pontine nucleus, the parvocellular and lateral reticular and spinal trigeminal
      nuclei by postnatal days 10 and 13, but decreased from this peak to equivalent to
      adult levels by postnatal day 28. The differential and transient expression of
      the natriuretic peptides during postnatal development, together with previous
      reports of the ontogenic regulation of natriuretic peptide receptor expression
      and binding patterns, further suggests their involvement in developmental
      processes in the rat CNS and provides information relevant to the likely
      functional development of natriuretic peptide-utilizing pathways.

PMID- 9541744
TI  - Ontogeny of mu opioid agonist anti-nociception in postnatal rats.
AB  - Mu opiate agonists morphine, fentanyl and meperidine are administered short-term
      to pediatric patients, from the neonatal period through adolescence. However,
      there has been no assessment of the effect of age on the analgesic efficacy or
      the concentration-response relationship for these opioids in human pediatric
      patients. Few studies in animals have correlated opioid anti-nociception and
      tissue levels of these opioids commonly administered to pediatric patients. The
      present study was conducted to examined the role of age on opioid anti
      nociceptive potency and efficacy and brain and plasma opioid levels to provide
      predictive information on the effect of opioids in developing humans.
      Administration of trace amounts of tritiated drug with anti-nociceptive doses of
      unlabeled drug was used for the assessment of anti-nociception in the tail-flick
      test and for the measurement of brain and plasma drug equivalent levels in
      postnatal rats (PND 3-21). Morphine and fentanyl were completely efficacious in
      all postnatal ages examined, although age-related differences in drug potency, as
      well as, differences in brain and plasma levels were observed. There was a good
      correlation between morphine (r = 0.96) and fentanyl (r = 0.89) ED(50) values and
      their respective brain and plasma EC(50) equivalent levels. Meperidine had
      limited efficacy in young rats (PND 3-9) but was completely efficacious in older
      rats (PND 14-17). However, PND 21 rats experienced tonic-clonic seizures which
      limited its efficacy to 70% anti-nociception. Our data suggest that
      pharmacokinetics, the development of the blood-brain barrier and ontogeny of
      opioid receptor function may play important roles in the sensitivity of postnatal
      rats to mu receptor agonists.

PMID- 9541745
TI  - BDNF accelerates gene expression in cultured cerebellar granule neurons.
AB  - This study reports that in purified cultures of postnatal cerebellar granule
      cells, BDNF significantly accelerated GABAA receptor alpha 6 subunit (GABAA alpha
      6) mRNA expression, a marker for terminally differentiated cerebellar granule
      neurons, and also accelerated p21cip1 expression. p21cip1 is a general cyclin
      dependent kinase (Cdk) inhibitor that can inhibit progression through the cell
      cycle. Alternatively, the expression of p27kip1, another Cdk inhibitor closely
      related to p21cip1, is not modified by BDNF. In cultured granule cells, the
      increase in p21cip1 expression induced by BDNF occurred after dividing granule
      cells had left the cell cycle and thus was not required to direct granule neuron
      precursors out of the cell cycle. p21cip1 may have an alterative function during
      granule neuron terminal differentiation, separate from its ability to regulate
      cell cycle exit. This report shows that, in vitro, BDNF accelerates granule cell
      gene expression and may thus modulate cerebellar granule cell differentiation.

PMID- 9541746
TI  - Chronic hypoxemia causes extracellular glutamate concentration to increase in the
      cerebral cortex of the near-term fetal sheep.
AB  - Fetal hypoxia is an important cause of neurologic morbidity and mortality.
      Hypoxia-induced increase in extracellular glutamate concentration can lead to
      excitotoxic neuronal death in adults. The objective of this study was to test
      whether chronic fetal hypoxemia increases extracellular glutamate concentration
      in the unanesthetized intact cerebral cortex of the near-term fetal sheep.
      Microdialysis probes were implanted into the parasagittal parietal cortex and
      periventricular white matter of near-term fetal sheep. At 124 +/- 1 days of
      gestation, extracellular glutamate concentration was determined before and during
      24 h of fetal hypoxemia. Chronic hypoxemia was produced by tightening a vascular
      occluder placed around the maternal common iliac artery. Larger decreases in
      fetal arterial oxygen content were associated with larger increases in
      extracellular glutamate concentration in the parietal cortex (Kendall's tau =
      0.81, N = 7, p = 0.005). No such relationship was detected in the periventricular
      white matter. Chronic hypoxemia increases extracellular glutamate concentration
      in the intact cerebral cortex of the unanesthetized near-term fetal sheep.

PMID- 9541747
TI  - Neonatal sex hormones have 'organizational' effects on the hypothalamic-pituitary
      adrenal axis of male rats.
AB  - Sex hormones have activational effects on the hypothalamic-pituitary-adrenal
      (HPA) axis in adulthood: For example, corticosterone release is influenced by
      gonadal status. These experiments investigated whether sex hormones have
      organizational effects on the HPA axis of male rats: Do sex hormones have
      relatively permanent effects on its development? In adults, both neonatal
      (neoGDX) and adult gonadectomy (adult GDX) resulted in elevated corticosterone
      (CORT) levels in response to stress compared to intact rats. Five days of
      testosterone propionate (TP) replacement was not as effective at attenuating CORT
      levels in neoGDX rats as in adult GDX rats. Neonatal GDX elevated corticosterone
      binding globulin (CBG) levels, whereas adult GDX was without effect. In
      Experiment 2 the effects of neonatal gonadectomy and neonatal treatment with
      either TP, estradiol benzoate (EB), or oil vehicle was examined. Despite 14 days
      of hormone replacement, neoGDX showed elevated CORT levels in response to stress
      compared to all other groups. A single neonatal dose of TP or EB in neoGDX rats
      eliminated the increased responsiveness. Neonatal TP and EB were without effect
      in sham-operated rats. Plasma CBG levels were elevated in neoGDX groups
      regardless of neonatal hormone treatment. Corticosteroid receptor binding levels
      were examined in various brain areas and the pituitary in two groups most
      different in their androgen experience: NeoGDX and shams that did not receive
      treatments as adults. NeoGDX had lower levels of glucocorticoid receptor, and
      higher levels of mineralocorticoid receptor binding in the pituitary. No other
      receptor differences were found. These experiments suggest that neonatal sex
      hormones influence the sensitivity of the HPA axis to sex hormones in adulthood
      and, thus, that they have organizational effects in addition to activational
      effects on HPA function.

PMID- 9541748
TI  - A critical maturational period of reduced brain vulnerability to developmental
      injury. I. Behavioral studies in cats.
AB  - Groups of cats with resection of the neocortex of the left cerebral hemisphere at
      postnatal (P) ages (in days) 5-15 (P10), 30 (P30), 60 (P60), 90 (P90), 120
      (P120), and in adulthood, were compared using a comprehensive battery of 16
      neurobehavioral tests administered when they were at least 6 months post-lesion.
      For all behaviors, except 3 (including the paw contact placing reaction which
      never recovered), the performance was significantly better for the cats lesioned
      between P10 and P30 compared to cats lesioned at older ages. For 10 of the
      behaviors, the transition from age-at-lesion P30 to P60 was rather abrupt and
      characterized by a significant increment in impairments. However, cats with the
      resection at ages P90 and P120 still showed some behavioral advantage over the
      adult-lesioned animals. Overall, for most of the behaviors tested, there was a
      significant linear trend for an increase in the magnitude of impairments across
      the entire age-at-lesion range. We previously reported that cats with a
      unilateral frontal cortical lesion sustained during the late fetal life showed
      substantial behavioral impairments, while animals with a similar resection
      sustained early postnatally exhibited minimal abnormalities. These findings,
      together with the present results, indicate that the long-term behavioral outcome
      of neocortical injury is best when the lesion is sustained during a discrete
      period of the life of the cat. This period extends from about fetal age 55 days
      (the oldest lesion age in our fetal studies) to about P60, as shown in the
      present paper. For these reasons, we propose that there is a Critical
      Maturational Period (CMP) for optimal post injury brain and behavioral
      restoration. We hypothesize that this span of reduced vulnerability is linked to
      specific developmental morphological events which occur during the same time
      period. Since, as discussed, such ontogenetic events also occur in other mammal
      species (albeit at different chronological ages), we further propose that the
      timing of the CMP as delineated in cats, can be extrapolated to other higher
      mammals species including humans.

PMID- 9541749
TI  - A critical period for reduced brain vulnerability to developmental injury. II.
      Volumetric study of the neocortex and thalamus in cats.
AB  - Groups of young adult cats with a left hemineodecortication at postnatal (P) ages
      (in days) 5-15 (P10), 30 (P30) 60 (P60), 90 (P90), 120 (P120) and in adulthood,
      were used to measure the volume of the thalamus, bilaterally, and of the
      remaining neocortex (right hemisphere). The same subjects were employed for the
      behavioral studies reported in the preceding paper. There was a bilateral, age
      dependent, thalamic volume decrease. Ipsilateral to the resection, the thalamic
      shrinkage was the largest for the adult-lesioned cats (by 56.7%) and it was the
      smallest for the P30 group (43.4%), with a tendency towards a greater atrophy as
      the age at lesion increased. A similar pattern of atrophy was seen for the
      contralateral thalamus but the volume reduction was much less pronounced such
      that it was significant only for the four older age-at-lesion groups (ranging
      from 18.2% to 11.2% for the P120 and P90 groups respectively). Once again, the
      shrinkage was the smallest for the P30 group (5.3%). The remaining neocortex also
      shrunk in these animals, but the volume decrease was significant only for the
      adult-lesioned (17.8%) and the P120 group (15.4%), while the P30 group had
      practically no shrinkage (2.4%). The frontal cortex had no atrophy or it was
      minimal but the shrinkage gradually increased caudally such that all lesioned
      groups had some size reduction of the occipital cortex. The present results,
      together with the main conclusion of the preceding paper, indicate that there is
      a critical maturation period (CMP) of reduced forebrain vulnerability to
      neocortical injury which, in cats, tends to end between 30 to 60 days
      postnatally. The implications for developmental brain damage in other higher
      mammal species as well as the possible morphological ontogenetical underpinnings
      of this period are discussed.

PMID- 9541750
TI  - An introduction to fuzzy systems.
AB  - We introduce the notion of fuzzy sets as a tool for modeling sets with ill
      defined or flexible boundaries. Fuzzy sets naturally appear when describing the
      meaning of natural language words pertaining to quantitative scales, or when
      modelling the notion of typicality. The three main semantics for fuzzy sets are
      recalled: similarity, preference and uncertainty. Each semantics underlies a
      particular class of applications. Similarity notions are exploited in clustering
      analysis and fuzzy controllers. Uncertainty is captured by fuzzy sets in the
      framework of possibility theory. The membership function of a fuzzy set is also
      sometimes a kind of utility function that represents flexible constraints in
      decision problems. Fuzzy sets are acknowledged as a major tool in information
      engineering for the purpose of bridging the gap between human-originated
      formalized knowledge, and numerical data.

PMID- 9541751
TI  - Fuzzy logic and inflammatory protein variations.
AB  - This tutorial style paper has been written for physicians and biologists who are
      not necessarily familiar with fuzzy set theory and biomedical applications. The
      field is introduced in the framework of medical diagnosis problems and
      illustrated with an application to inflammatory protein variations. The model is
      of special interest in the processing of borderline cases, allowing a graded
      assignment of diagnoses to patients. Relationships between signs and diagnoses
      are interpreted as labels of fuzzy sets and it is shown how diagnoses can be
      derived from soft matching processes. In cases of poor diagnostic classification,
      appropriate weights are introduced, acting on characterizations of signs, in
      order to decrease their relative influence. As a consequence, when pattern
      matching is achieved, the final ranking of inflammatory syndromes assigned to a
      given patient might change to better fit the actual classification.

PMID- 9541752
TI  - External quality assessment (EQA) of Belgian clinical laboratories. The
      telematics paradigm.
AB  - Technology that enables communication between information systems has recently
      become cheaper and more powerful. It is therefore timely to consider the effects
      of the introduction of such techniques in external quality assessment (EQA)
      schemes on both users and organizers. Traditionally, results are returned to EQA
      organizers as hand-written numbers on structured forms. These data are then
      manually entered into a computer. The process is time-consuming, slow (as it
      depends on the postal service), prone to error at every transcription stage, and
      expensive, as clerical staff must be employed to input the data. Computer-to
      computer communication allows this process to be improved. A telematics system
      for electronic data interchange has been developed for the Belgian EQA programme
      and it offers several advantages, such as the use of standardized semantics,
      expression of results in laboratory familiar units, possible interface with the
      Laboratory Information System, faster data analysis, shorter report time and long
      term performance evaluation.

PMID- 9541753
TI  - Laboratory cost control and financial management software.
AB  - Economical constraints within the health care system advocate the introduction of
      tighter control of costs in clinical laboratories. Detailed cost information
      forms the basis for cost control and financial management. Based on the cost
      information, proper decisions regarding priorities, procedure choices, personnel
      policies and investments can be made. This presentation outlines some principles
      of cost analysis, describes common limitations of cost analysis, and exemplifies
      use of software to achieve optimized cost control. One commercially available
      cost analysis software, LabCost, is described in some detail. In addition to
      provision of cost information, LabCost also serves as a general management tool
      for resource handling, accounting, inventory management and billing. The
      application of LabCost in the selection process of a new high throughput analyzer
      for a large clinical chemistry service is taken as an example for decisions that
      can be assisted by cost evaluation. It is concluded that laboratory management
      that wisely utilizes cost analysis to support the decision-making process will
      undoubtedly have a clear advantage over those laboratories that fail to employ
      cost considerations to guide their actions.

PMID- 9541754
TI  - Clinical case-based multimedia tutorials as a solution to some problems facing
      medical education.
AB  - Medical education faces many challenges as curricula become crowded and teacher
      numbers fall. In addition, there are moves to reduce factual overload and to
      concentrate more on pathophysiological principles illustrated by relevant
      clinical cases. We describe one means of addressing these problems, using
      computer-aided learning programs which are based on clinical cases, are
      interactive and which incorporate multimedia elements. These CD-ROM programs
      include student assessments, a resource of background material and support self
      managed and distance learning.

PMID- 9541755
TI  - Myocardial bridge as a cause of thrombus formation and myocardial infarction in a
      young athlete.

PMID- 9541756
TI  - Is coronary heart disease mortality really falling?

PMID- 9541757
TI  - The need for a prognosis trial of revascularization and aggressive medical
      therapy in patients with asymptomatic cardiac ischemia. ACIP Investigators.
      Asymptomatic Cardiac Ischemia Pilot.

PMID- 9541758
TI  - Current knowledge and significance of coronary artery ectasia: a chronologic
      review of the literature, recommendations for treatment, possible etiologies, and
      future considerations.
AB  - Coronary artery ectasia is the abnormal enlargement of the coronary artery. The
      prognosis, treatment, and etiology of this disease remain an enigma. There is
      some evidence to suggest that the incidence of ectasia is increasing, and
      therefore understanding of this entity needs to improve. This article reviews the
      current literature on coronary artery ectasia and summarizes the findings. A
      treatment plan that targets each of the suggested clinical complications is
      provided. Using multiple indirect observations and current understanding of
      endothelium-derived relaxation factor, a possible etiology that implicates
      overstimulation of endogenous nitric oxide is provided. Current literature
      suggests that ectatic coronary arteries, even without the presence of coronary
      stenosis, are subject to thrombus formation, vasospasm, and spontaneous
      dissection. Newer subgroups of ectasia are arising with the use of multiple
      interventional devices to dilate coronary artery stenosis. By design, these
      destroy the media of the coronary artery, and it is not clear whether these
      "iatrogenic" ectatic arteries are subject to the same complications as
      "idiopathic" coronary artery ectasia. Further investigation is necessary to help
      define the benefit of the proposed treatment regimen, to clarify the prognosis of
      these newer groups of "iatrogenic" ectasia, and to confirm or disprove the
      hypothesis targeting nitric oxide as an etiologic factor.

PMID- 9541759
TI  - Pathophysiologic bases for adjunctive therapies in the treatment and secondary
      prevention of acute myocardial infarction.
AB  - Postmyocardial infarction (MI) survival has been steadily improving. This
      improvement has been due, in part, to the actions of the adjunctive medical
      therapies for the treatment of MI. Aspirin, beta blockers, angiotensin-converting
      enzyme (ACE) inhibitors, and lipid-lowering agents have been shown to improve
      survival in the treatment and secondary prevention of MI. Nitrates have
      beneficial effects as well. These medications complement the reperfusion
      strategies through different mechanisms. Other adjunctive medical therapies,
      namely magnesium, antiarrhythmic agents, and calcium-channel blockers, have not
      been shown to improve mortality with routine post-MI use despite their
      theoretical benefits.

PMID- 9541760
TI  - Evaluation of left atrial filling using systolic pulmonary venous flow velocity
      measurements in patients with atrial fibrillation.
AB  - BACKGROUND: The pattern of pulmonary venous flow velocity is useful for
      understanding the hemodynamic relationship between the left atrium and left
      ventricle in patients with a variety of diseases, and the systolic flow wave, in
      particular, is considered a clinically important parameter that reflects left
      atrial filling. HYPOTHESIS: The study was undertaken to determine whether
      systolic pulmonary venous flow velocity patterns can be used to evaluate left
      atrial filling in patients with atrial fibrillation. METHODS: We performed
      transesophageal pulsed Doppler echocardiography and cardiac catheterization in 34
      patients with chronic atrial fibrillation (10 with hypertrophic cardiomyopathy, 5
      with dilated cardiomyopathy, 7 with previous myocardial infarction, and 12 with
      isolated atrial fibrillation) and 15 normal controls in sinus rhythm. RESULTS:
      Mean pulmonary capillary wedge pressure, V-wave height in the pulmonary capillary
      wedge pressure curve, and left ventricular end-diastolic pressure were
      significantly higher in the hypertrophic cardiomyopathy and dilated failing heart
      (previous myocardial infarction and dilated cardiomyopathy) groups than in the
      isolated atrial fibrillation and normal groups. The peak velocity and time
      velocity integral of the systolic pulmonary venous flow velocity, and percent
      left atrial emptying fraction were significantly lower in the dilated failing
      heart group than in the isolated atrial fibrillation, hypertrophic
      cardiomyopathy, and normal groups. The peak velocity and time-velocity integral
      of the systolic pulmonary venous flow velocity, percent left atrial emptying
      fraction, and V-wave height were comparatively constant when the preceding R-R
      intervals were relatively stable in the isolated atrial fibrillation group and in
      4 of the 10 patients with hypertrophic cardiomyopathy. However, changes in these
      variables correlated with the preceding R-R interval in all patients with dilated
      failing hearts and in 6 of the 10 patients with hypertrophic cardiomyopathy.
      CONCLUSION: Transesophageal pulsed Doppler echocardiographic measurements of
      systolic pulmonary venous flow velocity are valid indicators of left atrial
      filling in patients with atrial fibrillation.

PMID- 9541761
TI  - Identifying high yield sources of patients with coronary artery disease for
      clinical trials: lessons from the Asymptomatic Cardiac Ischemia Pilot (ACIP)
      experience. The ACIP Study Group.
AB  - BACKGROUND AND HYPOTHESIS: Successful recruitment strategies for ischemic heart
      disease (IHD) clinical trials must identify high yield sources and efficient
      methods for selecting patients likely to have coronary artery disease (CAD) and
      ischemia, but such information is lacking. METHODS: Data from the recently
      completed Asymptomatic Cardiac Ischemia Pilot (ACIP) Trial were used as a model
      contemporary CAD/IHD trial to determine the relative patient yields, within a
      specific time frame, for various recruitment sources. RESULTS: Over 15 months, a
      total of 88,881 patient records was screened at 10 sites. The highest yield
      source was found by screening records of patients directly referred by a
      physician for possible study entry. This source accounted for 595 of 814 or 73%
      of potential patients and for 30% of patients eventually randomized. The largest
      volume of potential patients was observed from coronary angiographic laboratory
      record screening, and this source accounted for 39% (n = 7.542) of potential
      patients and for 24% of those randomized. The exercise electrocardiography (ECG)
      laboratory patient records yielded only 16% (5,340/33,784) of potential patients
      and 35% of patients randomized, but this source required considerably more time
      and resources for screening. CONCLUSION: Considering that time and resources for
      screening are fixed by budget in any trial, there is a need to balance high
      volume-moderate yield sources with low volume-high yield sources in order to
      optimize recruitment in future larger scale trials, and these data provide
      information and direction to focus such screening efforts.

PMID- 9541762
TI  - Differences between male and female patients with regard to baseline demographics
      and clinical outcomes in the Asymptomatic Cardiac Ischemia Pilot (ACIP) Trial.
AB  - BACKGROUND: Coronary artery disease (CAD) is a common problem in men and women;
      however, men and women with similar clinical presentations of myocardial ischemia
      may receive different revascularization treatments. HYPOTHESIS: Using the data
      base of the Asymptomatic Cardiac Ischemia Pilot (ACIP) trial, this study was
      undertaken to compare by gender the baseline demographic data and the clinical
      outcome results in patients randomized to various treatments in the ACIP study.
      METHODS: This randomized trial compared three treatment regimens [pharmacologic
      management of angina, pharmacologic management of angina and ambulatory
      electrocardiographic (ECG) evidence of ischemia, and revascularization--that is,
      angioplasty and coronary artery bypass surgery], in patients with known CAD,
      positive stress ECG tests, and ECG evidence of ischemia during 48 h ambulatory
      monitoring. In all, 558 patients were randomized, 79 of whom were women (mean
      age: men 61.6 years, women 60.6 years) Ambulatory ECG evidence of ischemia,
      clinical events, that is, death, myocardial infarction, hospital admission for
      coronary events, and exercise performance were monitored. RESULTS: Although of
      the same age as men at baseline, women had a higher prevalence of hypertension
      and diabetes. Women had less severe CAD by angiography and higher left
      ventricular ejection fractions. Men had longer exercise tolerance times on the
      treadmill. However, men and women had similar numbers and duration of ambulatory
      ECG ischemic abnormalities. Regarding revascularization, men more commonly
      underwent coronary artery bypass surgery (p = 0.025) while women underwent
      percutaneous transluminal coronary angioplasty more frequently (p = 0.10).
      Clinical outcomes were comparable in men and women, although the numbers of
      events were relatively small. CONCLUSIONS: Men and women of comparable age
      manifest CAD with similar ischemic ECG abnormalities seen on both exercise
      tolerance and ambulatory ECG examinations. In ACIP, women tended to have more
      risk factors for CAD and less severity in anatomical disease, which may explain
      why women are less likely than men to have coronary bypass surgery.

PMID- 9541763
TI  - The clinical implications (or lack thereof) of vegetations detected by
      echocardiography in patients not thought to have endocarditis.
AB  - BACKGROUND: The clinical impact of echocardiographic demonstration of a
      vegetation (Veg) in patients in whom infective endocarditis (IE) is not suspected
      has not previously been analyzed. HYPOTHESIS: In this study, an echocardiographic
      database was interrogated to test whether discovery of a vegetation by
      echocardiography should result in treatment for endocarditis if IE is not
      suspected. METHODS: In all, 2,750 serial transthoracic echocardiograms (TTE) were
      reviewed to generate a list of reports containing the word Veg or thickening
      (Thk). A chart review of cases identified the impact the report had on patient
      management. To analyze reader bias due to echocardiographic requests, stating
      "rule out Veg or IE" as the reason for the study, an additional 1,000 serial TTE
      requests were segregated into two groups with and without this term. The
      incidence of the terms Veg or Thk in TTE reports of these groups was tabulated.
      RESULTS: Of 2,750 reports, 20 contained the word Veg. Blood cultures were drawn
      in 16 of 20, with 7 of 16 being positive. Therapy for IE was initiated in 5 of 7
      patients with positive cultures. Of 1,000 requests reviewed in the second phase,
      24% of those with rule out Veg as the indication for TTE (n = 29) had Veg and 7%
      had Thk, while in 971 cases with other indications for TTE 0.2% had Veg and 9.3%
      had Thk. CONCLUSIONS: Clinicians disregard TTE demonstration of Veg if clinical
      suspicion for IE is low. It is not clear whether the initial echo request biases
      the interpretation.

PMID- 9541764
TI  - Validation of a decision support tool for the evaluation of cardiac arrest
      victims.
AB  - BACKGROUND: There is currently no well-accepted model for early and accurate
      prediction of neurologic and vital outcomes after cardiac arrest. Recent studies
      indicate that individuals with acute myocardial ischemia as the etiology for the
      arrest may benefit from early revascularization. HYPOTHESIS: This study was
      undertaken to examine whether the cardiac arrest score is valid for predicting
      outcomes upon arrival at the emergency department. METHODS: We previously
      developed a cardiac arrest score based on time to return of spontaneous
      circulation, initial systolic blood pressure, and level of neurologic alertness
      in 127 patients (derivation set). This score was prospectively applied to 62
      patients with similar clinical profiles (validation set). Utility of the score
      was evaluated by the area under the receiver operator characteristic curves (C)
      for both sets. Consistency was measured by using the alpha statistic applied to
      the cumulative survival at each ascending level of the score. RESULTS: The
      derivation and validation sets were similar with respect to baseline
      characteristics and proportions at each level of score. The survival to discharge
      was 41.7 and 53.2% for the two sets, respectively. The value of C was 0.89 +/-
      0.03 and 0.93 +/- 0.03 for neurologic recovery and 0.81 +/- 0.04 and 0.92 +/-
      0.04 for survival to discharge in the two sets, respectively. The level of
      agreement between the sets across the levels of the score was 0.98 and 0.99 (both
      p < 0.0001) for the two outcomes. CONCLUSIONS: The cardiac arrest score is a
      valid decision support tool in the evaluation of cardiac arrest victims. Patients
      with the most favorable scores may be considered for early angiography and
      revascularization if myocardial ischemia is the etiology of the arrest.

PMID- 9541765
TI  - QT-interval dispersion in malnourished children.
AB  - BACKGROUND: Little is known about the electrocardiographic (ECG) QT interval and
      its variability in malnourished children. HYPOTHESIS: The study of the QT
      interval and its dispersion in malnourished children was undertaken to determine
      whether the QT interval and its variability are increased in these children.
      METHODS: In 40 children (20 malnourished and 20 controls) aged 12.2 +/- 14.4
      months (23 male) a conventional ECG was performed for computing heart rate, heart
      rate variability, corrected QT interval, and QT-interval dispersion. A blood
      sample was obtained for measuring hemoglobin, hematocrit, plasma protein, and
      plasma electrolytic concentrations. RESULTS: Corrected heart rate, heart rate
      variability, and QT Interval were similar in both groups. When compared with the
      control group, the malnourished children had greater corrected QT-interval
      dispersion, and that dispersion was more accentuated in the precordial leads.
      They also had repolarization abnormalities (flattened or inverted T waves and U
      waves). Hemoglobin, hematocrit, plasma protein, and plasma electrolytic
      concentrations were lower in the malnourished children. However, the ECG findings
      showed no statistically significant relationship with either the blood
      parameters, the severity or type of malnutrition, and the size or the weight of
      the children. CONCLUSIONS: QT-interval dispersion is increased in malnourished
      children and the dispersion is more accentuated in the precordial leads.

PMID- 9541766
TI  - Unstable angina: specialty-related disparities in implementation of practice
      guidelines.
AB  - BACKGROUND: The agency for Health Care Policy and Research (AHCPR) has published
      practice guidelines to improve the quality of care patients with unstable angina.
      Prior to publication, studies demonstrated that when compared with cardiologists,
      internists were less likely to use effective pharmacologic therapies or
      revascularization in patients with unstable angina. HYPOTHESIS: The study was
      undertaken to determine whether the AHCPR guideline publication abolished
      specialty-related disparities in care. METHODS: We performed a chart review of
      consecutive patients hospitalized at a university-affiliated institution with an
      admission diagnosis of chest pain in the absence of myocardial infarction and a
      noncardiac etiology. Treatment and diagnostic cardiac testing were compared
      between risk-stratified patients cared for by a generalist (n = 125) and those
      whose care was guided by a cardiologist (n = 211). RESULTS: In those with low
      risk unstable angina, generalists were less likely to prescribe recommended
      aspirin (71 vs. 88%, p < 0.01) and beta blockers (9 vs. 37%, p < 0.001), and
      heparin (20 vs. 49%, p < 0.001), and to perform a recommended diagnostic stress
      test or cardiac catheterization (28 vs. 60%, p < 0.001). In those with at least
      intermediate risk, generalists were less likely to prescribe beta blockers (19
      vs. 52%, p < 0.001), heparin (19 vs. 66%, p < 0.001), and nitrates (77 vs. 96%, p
      < 0.001), and to refer for diagnostic testing (19 vs. 65%, p < 0.001).
      Generalists' care was associated with significantly lower hospital charges.
      CONCLUSIONS: AHCPR guidelines for the evaluation and treatment of unstable angina
      are implemented more effectively, but not uniformly, by cardiologists at our
      institution. Further studies are necessary to evaluate the barriers to
      implementation of the AHCPR guidelines.

PMID- 9541767
TI  - Electrocardiographic crotchets or common errors made in the interpretation of the
      electrocardiogram.
AB  - Irritating errors are called crotchets. This paper discusses the following
      electrocardiographic crotchets: memorizing patterns rather than using basic
      principles, failure to use the electrocardiogram as a diagnostic tool, failure to
      correlate all available data, failure to appreciate the limitation of the
      computer interpretation, failure to appreciate the diagnostic value of P-wave
      abnormalities, the identification and misuse of abnormal Q waves, the misuse of
      left or right axis deviation of the QRS complexes, the misuse of the amplitude of
      the QRS complexes as a sign of left ventricular hypertrophy, identification of
      left ventricular hypertrophy, failure to identify uncomplicated and complicated
      bundle-branch block, failure to identify secondary and primary T-wave
      abnormalities, failure to identify secondary and primary S-T abnormalities, and
      lack of knowledge of the U waves.

PMID- 9541768
TI  - Hormones and the cardiologist.
AB  - Cardiologists must become more involved in discussing and recommending hormone
      replacement in post-menopausal women with established coronary artery disease,
      and those individuals at high risk of coronary events. A large amount of
      epidemiologic and observational data, as well as new research in vascular
      biology, strongly support the benefits of estrogen on the development and
      progression of coronary atherosclerosis. While breast and uterine cancer are
      valid concerns, selected high-risk women with and without established coronary
      disease should be counseled by an informed cardiologist to consider hormone
      replacement therapy.

PMID- 9541769
TI  - Images in cardiology. Pericardial cyst.

PMID- 9541770
TI  - Left ventricular diastolic collapse in low-pressure cardiac tamponade.
AB  - A case of systemic hypotension with volume depletion not responding to
      intravenous fluids was found to have features of cardiac tamponade on two
      dimensional (2-D) echocardiography. Intracardiac pressures were normal on cardiac
      catheterization. An interesting observation was the presence of left ventricular
      (LV) collapse on 2-D echocardiography. To the authors' best knowledge, such a
      case of low pressure cardiac tamponade with LV collapse has not been reported
      earlier.

PMID- 9541771
TI  - Hypocalcemic heart failure: a reversible form of heart muscle disease.
AB  - This paper reports the case of a 53-year-old woman with hypocalcemia-induced
      reversible cardiomyopathy. Laboratory tests showed hypocalcemia caused by
      idiopathic hypoparathyroidism. Her left ventricular dysfunction persisted for a
      long period even after normalization of the serum calcium level. Observations
      suggest that physicians should be aware that hypocalcemia can be a reversible
      cause of cardiomyopathy and congestive heart failure.

PMID- 9541772
TI  - George J. Guthrie.

PMID- 9541773
TI  - Representational flexibility and response control in a multistep multilocation
      search task.
AB  - Three experiments were conducted to explore the determinants of 2-year-olds'
      perseverative errors in a search task. In Experiment 1, children either retrieved
      an object during a preswitch phase or merely observed a hiding event. Active
      search produced perseveration on postswitch trials, but mere observation did not.
      In Experiment 2, similar results were found, even when active search occurred in
      the absence of observation. Finally, in Experiment 3, children observed a hiding
      event at 1 location on some pretest trials and simply retrieved an object at a
      different location on other trials. On test trials, in which an object was hidden
      at a 3rd location, children tended to search where they had searched previously.
      Together, the results indicate that active search is required to elicit
      perseveration, which points to failures of response control rather than
      representational inflexibility.

PMID- 9541774
TI  - Intersensory experience and early perceptual development: postnatal experience
      with multimodal maternal cues affects intersensory responsiveness in bobwhite
      quail chicks.
AB  - Unlike the other sensory modalities of precocial infants, the visual modality
      does not normally become functional until after birth or hatching. Despite this
      unique developmental status, the role of emerging visual experience on postnatal
      perceptual organization remains unclear. In this study, bobwhite quail hatchlings
      were reared in conditions that manipulated postnatal experience with maternal
      visual cues, either alone or in conjunction with maternal auditory cues. Results
      revealed that bobwhite chicks require postnatal exposure to both maternal
      auditory and visual cues following hatching to demonstrate species-specific
      perceptual preferences. Chicks that received temporally disparate maternal
      auditory and visual cues or experience with only maternal visual or maternal
      auditory cues failed to show species-typical perceptual responsiveness. These
      results suggest that developmental mechanisms involving both visual and auditory
      sensory experience underlie the emergence of early intersensory integration.

PMID- 9541775
TI  - On having complex representations of things: preschoolers use multiple words for
      objects and people.
AB  - Applying several names to an entity (polynomy) reflects the ability to categorize
      entities in different ways. Two experiments demonstrate preschoolers' abilities
      to apply multiple labels to representational objects and to people. In Experiment
      1, 3- and 4-year-olds labeled representational objects and verified labels for
      story characters. In both tasks children reliably produced or accepted several
      words per entity and accepted a high percentage of both class-inclusive and
      overlapping word pairs. These results were replicated in Experiment 2; 3- to 5
      year-olds also completed appearance-reality and receptive vocabulary tests. The
      mean number of words produced in the labeling task was significantly related to
      receptive vocabulary, but not to appearance-reality performance. The results
      indicate that preschoolers represent an entity as belonging to multiple
      categories (e.g., dinosaur and crayon). Implications for cognitive and language
      development, particularly the appearance-reality distinction and the mutual
      exclusivity bias, are discussed.

PMID- 9541776
TI  - Perception of motherese in Japanese sign language by 6-month-old hearing infants.
AB  - N. Masataka (1996) reported results of an experiment in which 6-month-old deaf
      infants were presented with videotapes that showed 5 identical scripts signed in
      Japanese Sign Language by 5 deaf mothers toward their deaf infants or toward
      their deaf friends. The experiment demonstrated that infants showed greater
      attentional and affective responsiveness to infant-directed signing than to adult
      directed signing. The present study explored the possibility that this same
      phenomenon might extend to hearing infants who have never been exposed to signed
      language. When the same stimulus tape as used previously was presented to 45 six
      month-old hearing infants, they too showed greater attentional and affective
      responsiveness to infant-directed sign than to adult-directed sign. This fact
      suggests that infants are prepared to detect sign motherese characteristics
      without specific experience in the modality.

PMID- 9541777
TI  - Infants' acquisition of spatiotemporal expectations.
AB  - The microdevelopment of infants' visual expectations was examined by analysis of
      the eye movements that 80 three-month-old human infants made during interstimulus
      intervals (ISIs) of an alternating picture sequence. For comparison, identical
      eye movement data were gathered from 10 infants who watched an irregular
      sequence. Shifts during ISIs were exhibited by all infants and occurred on 48% of
      all trials. Initially, infants' ISI shifts repeated saccades that had
      successfully located the preceding picture; during the course of the alternating
      session, repetitive saccades declined while alternating and anticipatory saccades
      increased. For infants who saw the irregular sequence, the frequency of ISI
      shifts did not vary systematically over trials. Analysis of saccade latencies
      suggested that infants quickly learned to inhibit a prepotent tendency in order
      to execute task-appropriate saccades.

PMID- 9541778
TI  - Children's perception of continuous and discontinuous movement.
AB  - The significance of E.S. Spelke and colleagues' (E.S. Spelke & C. Hofsten, 1986;
      E.S. Spelke & R. Kestenbaum, 1986; E.S. Spelke, R. Kestenbaum, D.J. Simons, & D.
      Wein, 1995) results that conflict with J. Piaget's (1952, 1955) theory of the
      object concept development was examined by a modified replication of E.S. Spelke
      and R. Kestenbaum's study. The present study involved 2- to 4-year-olds and
      events consisting of teddy bear pictures moving along a continuous or
      discontinuous course, with entering and exiting figures identical (ID) to or
      different (DIF) from one another. Forty participants in each age group saw all
      events in random order and gave verbal interpretations. The authors judged ID
      events as involving 1 object and DIF events as involving 2 objects. Continuity of
      movement failed to affect judgments of numerical identity. Implications for
      Piaget's theory and Spelke's theory are discussed.

PMID- 9541779
TI  - Fathers and preschool behavior problems.
AB  - Fathers have seldom been the focus of research investigating the causes and
      correlates of early behavior problems. Two studies examined fathers of preschool
      boys with and without clinic-referred behavior problems. Six domains of risk were
      examined: life stress, social support, psychological symptoms, parenting
      attitudes, positive involvement, and harsh discipline. Clinic fathers differed
      from fathers of matched comparison boys with respect to all of these except
      social support, but only harsh discipline contributed uniquely to clinic status.
      These domains correctly classified 81% of the boys. Within the clinic group,
      teacher-rated problem severity 1 year later was predicted by fathers' life
      stress, psychological symptoms, and positive involvement, indicating that
      different factors may account for initial clinic status versus stability of
      problems. Mothers' self-report data better predicted clinic group membership,
      whereas fathers' data better predicted Year 2 outcomes for clinic boys.

PMID- 9541780
TI  - Teacher discipline and child misbehavior in day care: untangling causality with
      correlational data.
AB  - Day-care centers provide an ideal, underused setting for studying the
      developmental processes of child psychopathology. The influence of day-care
      teachers' lax and overreactive discipline on children's behavior problems was
      examined, as was the influence of children's behavior problems on teachers'
      discipline. Participants were 145 children and 16 day-care teachers from 8
      classrooms in a day-care center for children from low-income families. Two
      techniques are presented for estimating causal relations based on correlational
      data gathered from day-care centers: 2-stage least squares and simultaneous
      structural equation modeling. Across techniques, teachers' laxness strongly
      influenced child misbehavior, and child misbehavior influenced both teachers'
      overreactivity and laxness. Teachers' overreactivity did not influence child
      misbehavior

PMID- 9541781
TI  - Observed sibling interaction: links with the marital and the mother-child
      relationship.
AB  - The study examines whether the link between the marital relationship and sibling
      interaction is direct or mediated by the mother-child relationship. Seventy-three
      same-sex siblings pairs aged 3 years 6 months to 8 years 6 months were observed
      during free play. Mothers completed questionnaires assessing marital functioning
      and their relationship with their 2 children. Results indicated that older
      siblings' negative behavior is linked with negative dimensions of the marital and
      the mother-child relationship, whereas younger siblings' negative behavior is
      linked with the mother-child and the differential mother-child relationship.
      Siblings; positive behavior, although linked with spacing, is not linked with
      positive dimensions of family interaction. Most important, the linkage between
      negative marital relations and older siblings; negative behavior was found to be
      mediated by maternal power assertion, thereby supporting the indirect model of
      negative family interaction.

PMID- 9541782
TI  - Does low self-regard invite victimization?
AB  - Two hypotheses were tested. The first was that low self-regard contributes over
      time to victimization by peers. The second was that behavioral vulnerabilities
      (e.g., physical weakness, manifest anxiety, poor social skills) are more likely
      to lead to victimization over time when children have low self-regard than when
      they are "self-protected" by healthy self-regard. Participants were 189 third
      through 7th-grade boys and girls; data were collected in the fall and the spring
      of the school year. Both hypotheses were supported, especially when self-regard
      was assessed in terms of self-perceived peer social competence. In addition, the
      experience of being victimized led to diminished self-regard over time. Poor self
      concept may play a central role in a vicious cycle that perpetuates and
      solidifies a child's status as a victim of peer abuse.

PMID- 9541783
TI  - Young children use motive information to make trait inferences.
AB  - The present study investigates children's capacity to understand traits in a
      psychologically meaningful way. Participants included 18 individuals in each of 4
      age groups: kindergarten (ages 5-6), 2nd grade (ages 7-8), 5th grade (ages 10
      11), and adult. They heard a series of 6 short stories in which a main character
      performs an action based on a particular motive (positive, negative, or
      incidental) that results in either a positive or a negative emotional consequence
      for another character. Participants evaluated each main character and predicted
      the character's behavior and mental states in different social contexts.
      Participants in all age groups, even the 5- to 6-year-olds, made trait inferences
      that were influenced by motive information. These results provide evidence that
      young children are capable of more sophisticated reasoning about traits than has
      been suggested previously.

PMID- 9541784
TI  - Children's understanding of extended identity.
AB  - As adults, we appreciate that judgments of us may reflect our associations with
      other people. This article examines the development of "extended identity" (G.R.
      Semin & K. Papadopoulou, 1989) in children between 5 and 11 years. In Experiment
      1, children were presented with hypothetical scenarios in which they imagined a
      close associate had committed a rule violation in a highly public context. Only
      the older children judged that they would be evaluated negatively through their
      association with the wrongdoer and that they themselves would feel embarrassment.
      Given the late appearance of extended identity, Experiment 2 addressed contexts
      in which the child was responsible for a younger child, so that accountability
      for the other was explicitly demanded. In such contexts, an appreciation of
      extended identity appeared earlier than it did in Experiment 1, in which no
      responsibility for the other was involved.

PMID- 9541785
TI  - Preschoolers' understanding of lies and innocent and negligent mistakes.
AB  - It has often been proposed that young children are not capable of distinguishing
      mistakes from lies and that they do not discriminate between the reactions that
      are generated by innocent and negligent mistakes. In our investigation, children
      aged 3 to 5 years were asked to choose whether a perpetrator had made a mistake
      or had lied about a food's contact with contaminants and were required to
      indicate whether this choice would produce a neutral or a negative reaction in
      the facial expression of a bystander. In this context, many children
      distinguished mistakes from lies and displayed an incipient ability to
      discriminate between lies and negligent mistakes that often generate negative
      reactions and innocent mistakes that do not.

PMID- 9541786
TI  - On the development of conscious and unconscious memory.
AB  - The distinction between conscious and unconscious memory, which is central to
      modern theories of cognition, has received only limited scrutiny in developmental
      research. One reason is a need for developmental methodologies that allow age
      variability in conscious and unconscious memory to be quantified. A simple
      paradigm (called conjoint recognition) and model are presented that quantify
      conscious and unconscious memory for learned materials and for the types of
      unlearned materials that have been found to induce false memories in children. A
      validation study showed that the model gave excellent accounts of the performance
      of 7- and 10-year-olds and that conscious and unconscious memory parameters
      reacted in appropriate ways to 3 manipulations (age, meaningfulness of
      distractors and targets, and priming).

PMID- 9541787
TI  - The getting of wisdom: theory of mind in old age.
AB  - Theory of mind, the ability to attribute mental states, has been little explored
      beyond the early school years. Yet, later development, including possible
      patterns of breakdown, has important implications for current debate concerning
      the modularity/domain-specificity of the cognitive and neurological systems
      underlying theory of mind. This article reports a first study of theory of mind
      in normal aging. The results suggest that although performance on tasks with
      nonmental content may decrease with age, performance on theory of mind tasks
      remains intact and may even improve over the later adult years. The implications
      of these findings for the cognitive processes underlying theory of mind are
      discussed.

PMID- 9541788
TI  - Disentangling early language development: modeling lexical and grammatical
      acquisition using an extension of case-study methodology.
AB  - The early lexical and grammatical development of 1 male child is examined with
      growth curves and dynamic-systems modeling procedures. Lexical-development
      described a pattern of logistic growth (R2 = .98). Lexical and plural development
      shared the following characteristics: Plural growth began only after a threshold
      was reached in vocabulary size; lexical growth slowed as plural growth increased.
      As plural use reached full mastery, lexical growth began again to increase. It
      was hypothesized that a precursor model (P. van Geert, 1991) would fit these
      data. Subsequent testing indicated that the precursor model, modified to
      incorporate brief yet intensive plural growth, provided a suitable fit. The value
      of the modified precursor model for the explication of processes implicated in
      language development is discussed.

PMID- 9541789
TI  - Natural and artifactual kinds: are children realists or relativists about
      categories?
AB  - Research in cognitive development has highlighted important differences between
      conceptions of natural kinds and artifacts. One interpretation of the distinction
      is that natural kinds are categories one discovers, whereas artifactual kinds are
      invented. Four studies assessed whether children and adults saw categorization
      decisions as objective matters of fact or as invented conventions. Preschool-age
      children treated basic-level categories of animals and human-made artifacts as
      objective. At the superordinate level, kinds of animals were treated as more
      objective than were kinds of artifacts. In general, adults' judgments were
      similar to children's. Both children and adults have reliable and differentiated
      intuitions regarding category objectivity. The results from these studies are
      discussed in terms of their implications for structural and theory-based accounts
      of category naturalness.

PMID- 9541790
TI  - [A binary system of oligonucleotide derivatives of perylene and n
      azidotetrafluorobenzalhydrazone for DNA photomodification sensitized to visible
      light].

PMID- 9541791
TI  - [Spatial structure of the photosynthetic bacterium Rhodopseudomonas viridis B1015
      complex].

PMID- 9541792
TI  - [Characteristics of the neuroprotective activity of triterpene glycosides and the
      composite "Zhensolar", based on them].

PMID- 9541793
TI  - [(Arg8)-vasopressin stimulates insulin synthesis in pancreatic beta cells during
      chronic intracerebroventricular administration to intact and diabetic rats].

PMID- 9541794
TI  - [Quantum analysis does not confirm the increase in sensitivity of postsynaptic
      receptors in the late phase of hippocampal long term potentiation].

PMID- 9541795
TI  - [Effect of C-26 biopolymer on rat systemic hemodynamics].

PMID- 9541796
TI  - [Cortical modulation of the gastric motor reaction, caused by activating the
      vasovagal reflex arc].

PMID- 9541797
TI  - [Level of chromosomal variability in somatic cells of children, living in
      agricultural regions].

PMID- 9541798
TI  - [Association of muscle glycogen phosphorylase b by equilibrium sedimentation
      methods].

PMID- 9541799
TI  - [Vestibular nucleus neurons, projecting to the "gastric" area of the solitary
      tract nucleus].

PMID- 9541800
TI  - [Psychotropic activity--a new property of glycyrrhizic acid and its derivatives].

PMID- 9541801
TI  - [Intensification of the hydroosmotic effect of vasopressin with substances
      resistant to proteolysis].

PMID- 9541802
TI  - [Molecular genetic analysis of mitochondrial DNA of representatives of from the
      Pazyryk culture of Altai (IV-II centuries B.C.)].

PMID- 9541804
TI  - [Immunogenetic aspects of bovine phylogeny].

PMID- 9541803
TI  - [The Delta locus in Drosophila virilis: cloning and chromosome mapping].

PMID- 9541805
TI  - [A highly productive variant of the hepatitis C virus. Isolation, identification,
      characteristics].

PMID- 9541806
TI  - [Features of structural changes in hippocampal synapses of rats with various
      types of behavior in cerebral ischemia].

PMID- 9541807
TI  - [Human auditory evoked potentials during speech-voice activity].

PMID- 9541808
TI  - [Assessment of beta-adrenergic reactivity of erythrocytes by their sedimentation
      rate in the presence of adrenergic agents].

PMID- 9541809
TI  - [Effect of population stress on the frequency of white-spotted water voles
      (Arvicola terrestris L.)].

PMID- 9541810
TI  - [Differential scanning calorimetric study of irreversible heat denaturation of
      uridine phosphorylase from Escherichia coli K-12].

PMID- 9541812
TI  - [Effect of Tritonia neuropeptides and serotonin on ciliary activity].

PMID- 9541811
TI  - [Participation of the bacterial respiratory chain in reduction of potassium
      tellurite].

PMID- 9541813
TI  - [Recovery of physical capability of rats after blood loss, using the polyethylene
      oxide Polyox WSR-301].

PMID- 9541814
TI  - [Sensory connection of the cat stellate ganglion].

PMID- 9541815
TI  - [Myelopeptide-3--a bone marrow mediator, stimulating macrophage phagocytic
      activity].

PMID- 9541816
TI  - [Novelty as a factor and scent marking of territory by gerbils].

PMID- 9541817
TI  - Topical fundus pulsation measurements in age-related macular degeneration.
AB  - BACKGROUND: The purpose of the present study was to investigate regional fundus
      pulsations in age-related macular degeneration (AMD) patients with subretinal
      neovascular membranes. METHODS: Local fundus pulsation amplitudes (FPAs) were
      measured in 12 patients with AMD with classic neovascular membranes. Measurements
      were performed directly on the membrane and adjacent to the membrane. FPAs were
      assessed with a recently developed laser interferometric method. FPA measurements
      were performed in 12 healthy subjects at similar posterior pole locations.
      RESULTS: In AMD patients FPAs were consistently lower when measured directly on
      the neovascular membrane ("inside") than at measurement sites around the membrane
      ("outside"). The difference in FPA was 26 +/- 3% (mean +/- SEM, range 13-40%, P <
      0.0001). In healthy subjects, however, FPAs were significantly higher at the
      measurement points corresponding to "inside" points (15 +/- 4%, P < 0.0006).
      CONCLUSIONS: We have shown that FPAs are reduced at classic neovascular membranes
      in patients with AMD. The mechanism behind this finding remains unclear. Hence,
      future studies have to ascertain whether this observation is associated with
      changes in fundus layers or with local choroidal perfusion abnormalities.

PMID- 9541818
TI  - Results of treatment of choroidal malignant melanoma with high-dose-rate
      strontium-90 brachytherapy. A retrospective study of 46 patients treated between
      1983 and 1995.
AB  - PURPOSE: We review the results of treatment of small to medium-sized choroidal
      malignant melanomas after high-dose-rate brachytherapy with a strontium-90
      applicator. METHODS: The applicator is positioned against the sclera using an
      afterloading technique. Brachytherapy is completed in a single session lasting 2
      4 h with the patient under local anaesthesia. From September 1983 until March
      1995, 46 eyes were treated in this way. Most tumours were 7-11 mm in diameter
      (range from 4.5-15 mm) with a mean height of approximately 3 mm (range from 1.5-7
      mm). Follow-up ranged from 6 months to 12 years (mean 49 months). RESULTS: Thirty
      of the 46 eyes had at the final evaluation a nonevolutive scar (20 of these after
      a single application, the others with some additional treatment). In 13 eyes the
      tumours were in involution but their complete destruction was not yet certain,
      and 3 eyes were enucleated for local recurrence. Three patients developed
      systemic metastases. No radiogenic complications were noticed. CONCLUSION:
      Strontium-90 brachytherapy is a valuable and safe treatment technique for small
      to medium-sized choroidal malignant melanomas. In addition the use of a strontium
      90 applicator is inexpensive thanks to this element's long half-life and the
      short application time.

PMID- 9541819
TI  - Chorioretinal venous anastomoses: effect of different laser methods and energy in
      human eyes without vein occlusion.
AB  - BACKGROUND: This study was performed to determine the laser energy required to
      rupture both Bruch's membrane and retinal veins reliably in order to create a
      venous chorioretinal anastomosis. METHODS: A histological examination was
      conducted of argon green and YAG laser applications to the retina made prior to
      enucleation in eight eyes with large intraocular melanomas. RESULTS: Argon laser
      application of 50 microns in size and 0.1 s duration to intervascular areas of
      the retina will reliably rupture Bruch's membrane at a power level of at least
      1.5 W. If the argon laser spot is placed overlying a retinal vein, a power level
      of up to 2.5-3.0 W will rupture Bruch's membrane in 60%, with only 34% of the
      retinal veins showing evidence of rupture. The YAG laser with power levels of 3-4
      mJ will reliably rupture the retinal vein in cases where it has not previously
      been ruptured by the argon laser. CONCLUSION: When attempting to create a
      chorioretinal venous anastomosis in an eye with a non-ischaemic central retinal
      vein occlusion, Bruch's membrane should be ruptured first by placing the argon
      laser application at the side of the retinal vein before an attempt to rupture
      the retinal vein itself is made in case haemorrhage from the ruptured vein
      obscures the view. A power level of at least 2.5 W should be used. If the argon
      laser is unsuccessful in rupturing the retinal vein, a YAG laser (3-4 mJ) is
      effective.

PMID- 9541820
TI  - Effects of different perfluorochemicals on dorsal root ganglion cells in vitro.
AB  - BACKGROUND: Investigation of the effects of different perfluorochemicals (PFC) on
      cultured dorsal root ganglion (DRG) cells. METHOD: DRG cell cultures from 9- to
      11-day-old chicken embryos were exposed to emulsified perfluorodecalin (PFD;
      C10F18; 0.5%, 1% and 10%) or perfluorooctylbromide (PFO; C8F17Br; 0.5%, 1% and
      10%). The cells were evaluated under phase-contrast optics after 30 h and 120 h
      for 0.5 and 1% and after 5 h for 10%. To study the integrity of neuronal cells,
      immunohistochemical labelling for neurofilaments (NF) and tubulin (TUB) was
      performed. RESULTS: Concentrations of 0.5% and 1% of PFD or PFO did not change
      immunohistochemical labelling of DRG cells. Co-cultured macrophages showed a foam
      cell response, presumably representing ingested PFC. At both concentrations PFD
      induced a weaker foam cell response than PFO. A concentration of 10% led to the
      death of DRG cells and macrophages within 5 h. CONCLUSION: PFC caused a dose
      dependent damage of neuronal cells. Co-cultured macrophages developed a foam cell
      response similar to that observed in vivo after prolonged presence of PFC in the
      vitreous body. These observations indicate that PFD and PFO may not be suitable
      for long-term vitreous replacement in vitreoretinal surgery. However, the model
      is limited by several factors: (1) there are physiological differences between
      DRG cells and retinal ganglion cells; (2) in vivo retinal ganglion cells are
      protected by the overlying tissues; (3) the PFC used in tissue culture must be
      emulsified.

PMID- 9541821
TI  - Visual field defects in optic neuritis and anterior ischemic optic neuropathy:
      distinctive features.
AB  - BACKGROUND: We analyzed the value of visual-field defects in the differential
      diagnosis of optic neuritis (ON) and non-arteritic anterior ischemic optic
      neuropathy (AION). METHODS: Ninety-nine consecutive patients with acute-onset
      optic neuropathy formed the basis for this study. Compressive and vasculitic
      neuropathies were excluded. Eighty-six patients fulfilled the criteria for either
      ON (50 patients): < or = 35 years, normal disk, recovery of visual function, or
      AION (36 patients): > or = 60 years, swelling of the disk, no recovery of visual
      function. Without knowledge of other clinical data, visual fields obtained by
      Gold-mann perimetry were classified into five types of defects (forced choice).
      With the correct diagnosis at hand, fields were reviewed for characteristic
      features. RESULTS: Forced-choice classification into defect types [%]: Central
      scotoma ON 68, AION 18; superior altitudinal defect ON 13 AION 7; inferior
      altitudinal defect ON 8, AION 52; peripheral defect ON 1, AION 5; diffuse defect
      ON 10, AION 18. Search for pathognomonic defects: a scotoma centered on the
      fixation point with a sloping border occurred exclusively in ON (25 of 50
      patients). An inferior altitudinal defect with a sharp border along the
      horizontal meridian, particularly in the nasal periphery, occurred only in AION
      (10 of 36 patients). A steep centrocecal scotoma occurred in 3 of the 36 AION
      cases and not at all in the ON cases. Scotomas in the center breaking through to
      the periphery, superior altitudinal defects (with a sloping border along the
      horizontal meridian) and diffuse depressions verging on blindness occurred in
      both ON and AION. CONCLUSION: A sctoma centered on the fixation point with a
      sloping border is highly characteristic of ON, while an inferior altitudinal
      defect with a sharp border along the horizontal meridian, particularly in the
      nasal periphery, is highly characteristic of AION. To identify these diagnostic
      criteria, it can be necessary to examine full fields. With restriction of
      perimetry to 30 degrees a large central scotoma can be mistaken for a diffuse
      defect and the border in the nasal periphery can be missed.

PMID- 9541822
TI  - Detection of choroidal aneurysms with indocyanine green videoangiography.
AB  - BACKGROUND: Aneurysms of the choroidal vasculature have been described only in
      histopathological studies. METHODS: Indocyanine green videoangiograms obtained
      with the scanning laser ophthalmoscope from 32 patients with geographic atrophy
      were reviewed. RESULTS: In 8 of 32 patients indocyanine green videoangiography
      (ICGVA) showed hyperfluorescent aneurysms along choroidal arteries. The same
      aneurysmal formations were found in two of the eight patients on very early
      images of fluorescein videoangiography before dye leakage occurred. Seven of
      eight patients with choroidal aneurysms had a history of hypertension.
      CONCLUSIONS: ICGVA is a useful diagnostic tool in detecting choroidal aneurysms.
      Multiple mechanisms are probably involved in the pathogenesis of choroidal
      aneurysms, among them the higher hemodynamic stress in the macular region,
      hypertension and aging.

PMID- 9541823
TI  - Subretinal administration of tissue-type plasminogen activator to speed the
      drainage of subretinal hemorrhage.
AB  - BACKGROUND: Bleeding into the subretinal space in the vicinity of the macula is
      associated with age-related macular degeneration or retinal arterial
      macroaneurysm. The prognosis for restoration of vision is poor in the presence of
      blood clots. METHODS: Using a simple device composed of three disposable syringes
      we injected tissue-type plasminogen activator (tPA) into the subretinal space
      during conventional vitrectomy in six patients to assist the draining of
      subretinal clots. RESULTS: Four of six patients recovered their visual acuity
      postoperatively, while visual acuity in the other patients was stabilized.
      CONCLUSION: Early drainage of subretinal hemorrhage assisted by the introduction
      of tPA into the subretinal space led to uncomplicated surgery and favorable
      postoperative results.

PMID- 9541824
TI  - Prevalence of diabetes mellitus and arterial hypertension in primary and
      secondary open-angle glaucomas.
AB  - BACKGROUND: This study was carried out to evaluate the prevalence of diabetes
      mellitus and arterial hypertension in the open-angle glaucomas. METHODS: The
      study consisted of 529 patients with primary open-angle glaucoma, including 170
      patients with the age-related atrophic type and 22 patients with the highly
      myopic type; 152 patients with secondary open-angle glaucoma, including 85
      patients with pseudoexfoliative glaucoma; 56 patients with the focal type of
      normal-pressure glaucoma; and 660 nonglaucomatous subjects in the control group.
      For all study groups, age-matched control groups were formed. RESULTS: Prevalence
      of diabetes mellitus and arterial hypertension did not vary significantly (P >
      0.25; chi-square test) between the non-highly myopic primary open-angle glaucoma
      groups and the control groups. In highly myopic primary open-angle glaucoma,
      pseudoexfoliative glaucoma, and focal normal-pressure glaucoma, diabetes mellitus
      and arterial hypertension were less common; however, not in all cases was the
      difference from the control group significant. CONCLUSIONS: The results suggest
      that diabetes mellitus and arterial hypertension are not more common in patients
      with primary and secondary open-angle glaucomas than in age-matched
      nonglaucomatous subjects. In agreement with some previous epidemiologic studies,
      diabetes mellitus and arterial hypertension may not be positively associated with
      the primary or secondary open-angle glaucomas.

PMID- 9541825
TI  - Apoptosis of photoreceptor cells in ornithine-induced retinopathy.
AB  - BACKGROUND: The intravitreal injection of ornithine produces selective damage to
      the retinal pigment epithelium (RPE) and results in a loss of RPE,
      choriocapillaris and photoreceptor cells. To elucidate the mechanism of secondary
      retinal atrophy, we investigated the presence of apoptotic cells in a rat model
      of ornithine-induced retinopathy. METHODS: At 6 and 12 h and 1, 2, 4, 7, 14 and
      28 days after an intravitreal injection of L-ornithine hydrochloride in rat eyes,
      we removed the eyes and subjected them to histopathological examination. We
      detected apoptotic cells by terminal deoxynucleotidyl transferase-mediated
      deoxyuridine triphosphate digoxigenin nick end labeling (TUNEL) assay, which
      stains the 3'-OH ends of fragmented DNA. We used electron microscopy to detect
      the apoptotic cells morphologically. RESULTS: RPE cells were selectively damaged
      immediately after ornithine administration. TUNEL-positive photoreceptor cells
      appeared exclusively in the photoreceptor cell layer 12 h after ornithine
      administration. The number of TUNEL-positive cells increased throughout the 2
      days following the injection, then decreased markedly. TUNEL-positive cells
      remained until 28 days, when the photoreceptor cells had disappeared. The
      ganglion cell layer, inner nuclear layer and damaged RPE cells were negative for
      TUNEL staining during all stages. The electron microscopic study also revealed
      the pyknotic nuclei of apoptotic photoreceptor cells. CONCLUSION: An intravitreal
      injection of ornithine caused primary damage to the RPE, and subsequently some of
      the photoreceptor cells revealed apoptosis by TUNEL assay. These findings suggest
      the dysfunction of the RPE causes photoreceptor cell death according to the
      intrinsic program of an apoptotic mechanism.

PMID- 9541826
TI  - Therapeutic range of repetitive nanosecond laser exposures in selective RPE
      photocoagulation.
AB  - BACKGROUND: The aim of this study was to investigate whether selective damage the
      RPE while sparing the adjacent photoreceptors is possible with repetitive 200-ns
      pulses of Nd:YAG laser (532 nm) and what potential side effects can be expected
      with higher pulse energies. METHODS: We irradiated the retinas of 19 eyes of 10
      chinchilla rabbits with 500 pulses from a Nd:YAG laser, each 200 ns in duration,
      at a repetition rate of 500 Hz (158 microns, 0-120 microJ). Threshold curves for
      different effects were established. Representative lesions were investigated by
      light and transmission electron microscopy. RESULTS: It was possible to produce
      lesions, which were only visible by fluorescein angiography. The ED50 threshold
      energy per pulse for visibility by fluorescein angiography was 2.1 microJ per
      pulse, for visibility by ophthalmoscopy 8.6 microJ. Bubble formation, an uncommon
      phenomenon in retinal photocoagulation, occurred at energies of 15-25 microJ.
      Hemorrhage occurred at surprisingly high energy levels of more than 100 microJ.
      Histology performed on lesions visible only by angiography showed damage
      primarily to the RPE and outer segments, with very little damage to some inner
      segments dependent on the energy used. CONCLUSIONS: Selective RPE damage is
      possible with repetitive 200-ns laser pulses and appropriate energy; however, the
      collateral damage to the adjacent retina is more pronounced than with repetitive
      microsecond laser pulses. There is no risk of hemorrhage of retinal
      photocoagulation with the repetitive 200-ns laser pulses at low energy levels
      which would be used clinically.

PMID- 9541827
TI  - Ability of retroviral transduction to modify the angiogenic characteristics of
      RPE cells.
AB  - BACKGROUND: Retinal pigment epithelial (RPE) cells play an important role in the
      modulation of ocular angiogenesis. Transduction of RPE cells with retroviral
      vectors bearing modulating genes can result in long-term transgene expression and
      may alter the angiogenic characteristics of RPE cells. This study was designed to
      determine whether changes in angiogenic characteristics of RPE cells result from
      transduction with retroviral vectors bearing modulating genes, using in vitro
      angiogenic assays, including analysis of endothelial proliferation and wound
      healing. METHODS: Human RPE cells were transduced with retroviral vectors bearing
      either a urokinase-type plasminogen activator (u-PA) or a tissue-type plasminogen
      activator (t-PA) cDNA. Ten weeks after gene transfer, RPE cells transduced with
      the u-PA (u-PA-RPE cells) or the t-PA cDNA (t-PA-RPE cells), or untransduced
      (control) RPE cells, were cocultured with human umbilical vein endothelial cells
      (HUVECs) by contacting and non-contacting coculture methods. The effects of these
      cells on proliferation and in vitro "wound healing" of HUVECs were evaluated.
      RESULTS: Over 18 weeks, u-PA-RPE cells released large amounts of biologically
      active u-PA (total amount, 50.2 +/- 9.7 ng/10(6) cells/24 h), while t-PA-RPE
      cells released large amounts of functional t-PA (15.4 +/- 3.2 ng/10(6) cells/24
      h). Control RPE cells did not release any detectable t-PA or u-PA. In the
      proliferation assay, u-PA-RPE cells stimulated HUVEC proliferation in contacting
      cell cultures, but not in non-contacting cell cultures. In contrast, t-PA-RPE
      cells, normal RPE cells or exogenous u-PA had no effect on HUVEC proliferation.
      In the wound healing assay, u-PA-RPE cells in contacting coculture and exogenous
      u-PA stimulated wound healing of HUVECs, while non-contacting u-PA-RPE cells, t
      PA-RPE cells and normal RPE cells had no effect on HUVEC wound healing. RPE cells
      transduced with u-PA secreted large amounts of u-PA for as long as 18 weeks, and
      these cells stimulate HUVEC proliferation and in vitro wound healing. As a
      result, the angiogenic characteristics of RPE cells can undergo long-term
      changes. CONCLUSIONS: These results suggest that genetically modified RPE cells
      can be used to modulate ocular angiogenesis and may have potential for gene
      therapy of ocular diseases.

PMID- 9541828
TI  - Photosensitization of retinal pigment epithelium by protoporphyrin IX.
AB  - BACKGROUND: Clinical evidence of injury to the retinal pigment epithelium is an
      important feature of age-related macular degeneration, but the mechanism of this
      injury is unknown. Blue-light-dependent activation of the blood-borne
      photosensitizer protoporphyrin IX is known to produce free radicals which may
      damage cells and tissues. This study was undertaken to determine the effect of
      blue light and protoporphyrin IX on retinal pigment epithelial cells in vitro.
      METHODS: Third-passage porcine retinal pigment epithelial cells were plated in
      six-well culture plates at 100,000 cells/well and grown to confluence. Retinal
      pigment epithelial cells were then incubated in culture media with and without 35
      micrograms/dl protoporphyrin IX and exposed to low intensity (118 microW/cm2)
      blue, blue-free, or full-spectrum white light in an irradiating incubator for 16
      h on/8 h off cycles for 7 days. Some of the wells were shielded from light (dark
      controls). Retinal pigment epithelial cells were examined by light microscopy and
      were trypsinized and counted after 7 days. RESULTS: White light with and without
      protoporphyrin IX and protoporphyrin IX in dark conditions did not decrease the
      retinal pigment epithelial cell count significantly. Blue light alone and blue
      light with protoporphyrin IX decreased the cell count by 22 +/- 4% and 35 +/- 3%
      compared to the controls, respectively. CONCLUSION: Blue wavelength light without
      exogenous protoporphyrin IX has a cytotoxic effect on confluent cultures of
      retinal pigment epithelium, suggesting that endogenous photosensitizers may be
      present in retinal pigment epithelial cells. Protoporphyrin IX has an additive
      cytotoxic effect in the presence of blue light, suggesting that this
      photosensitizer is capable of mediating blue-light-induced retinal pigment
      epithelial damage. Since protoporphyrin IX is present in blood and tissue fluids,
      and the retina is chronically exposed to light, protoporphyrin IX-mediated free
      radical formation may occur in vivo and may play a role in retinal pigment
      epithelial changes that occur early in the pathogenesis of age-related macular
      degeneration.

PMID- 9541829
TI  - Exchange of perfluorodecalin for gas or oil: a model for avoiding slippage.
AB  - BACKGROUND: The introduction of liquid perfluorocarbons as an intraoperative tool
      has greatly facilitated retinal re-apposition in giant retinal tears (GRT) and
      relieving retinotomies (RR). Slippage of the retina can occur during the exchange
      of heavy liquids for oil or gas, especially if the fill of perfluorocarbons is
      subtotal. METHODS: We have used a model eye chamber to study the surface
      interactions of perfluorodecalin (PFD) with silicone oil and air to evaluate
      possible mechanisms of slippage. RESULTS: The results demonstrate that it is
      possible during a PFD/air exchange to trap a wedge of aqueous which is displaced
      laterally and forced posteriorly during removal of the PFD, whereas during a
      PFD/silicone oil exchange the remaining aqueous is displaced laterally and
      upwards and thus trapped above the silicone oil/PFD interface. CONCLUSIONS: We
      believe that during PFD/air exchange the displacement of the aqueous posteriorly
      can cause slippage and that this could be avoided by performing a direct
      PFD/silicone oil exchange.

PMID- 9541830
TI  - Effects of eye muscle proprioceptive activation: morphological particularities of
      human extraocular muscle spindles.

PMID- 9541831
TI  - [Status quo of plastic surgery education in Austria].
AB  - Quality is essentially based on excellent training. Therefore, all medical
      disciplines in Austria, including the Plastic Surgery, have to orientate on EU
      standards including efforts to adapt the surgical training. To gain an overall
      impression of the present training situation in Austria, an anonymous
      questionnaire was sent to all the 25 trainees in Plastic Surgery in summer 1995.
      Eight centres were involved throughout the country. The questions covered quality
      of training, reference departments, rotation in training, and postgraduate
      studies, 52% of the questionnaires were sent back. The conclusions resulting from
      the questionnaires are the following: unrestricted passing of plastic surgery
      know-how, provision of reference departments, implementation of rotation for
      training, carrying out of all operations listed in the EU-catalogue, regular
      postgraduate training. Only in this way excellently trained plastic surgeons with
      a strong self confidence can be a convincing counterpole to other fields of
      surgery which increasingly lay claim to Plastic Surgery terrain.

PMID- 9541832
TI  - [Movements of the pisiform and triquetrum bones and their significance for
      kinematics of the ulnar wrist].
AB  - The purpose of this study is to investigate carpal kinematics with respect to the
      pisotriquetral joint, before and after pisi-form excision. Five cadaver-hands
      were studied and a custom-designed plexi-glass-fixation device was used to
      standardize the wrists for exact passive movements in flexion and extension as
      well as in ulnar and radial abduction. Five sets of motion were registered before
      and after excision of the pisiform. Motion of the triquetrum and pisiform were
      studied by 3D-Motion Analysing Software System (peak 54). The results indicated
      that the excision of the pisiform does have an influence on the kinematics of the
      wrist. The movement of the triquetrum was increased after removal of the
      pisiform. Although the differences in measurement were only a few of millimetres
      and degrees, we know from the dorsal and palmar intercalated segment
      instabilities that even minor instabilities can act as a predisposing factor for
      arthrosis. Therefore, the excision of pisiform must be carefully considered. The
      common joint between the triquetrum and pisiform supports and indicates relation
      of their movements. However, the correlation for flexion/extension and radial
      deviation was high, an obvious correlation of the movements for ulnar deviation
      was not verifiable.

PMID- 9541833
TI  - [Outcome in therapy of hand infections--are there differences between East and
      West Germany?].
AB  - In 564 patients treated at the University of Magdeburg Medical School, we
      evaluated the timing of surgical intervention and the use of systemic antibiotics
      and their influence on recovery and treatment results. Special attention was paid
      to the question if there are any differences between East- and West-German
      treatment results. While early surgical intervention and radical debridement are
      the most important factors for complete recovery, differences in the availability
      and use of antibiotics did not play a significant role in results.

PMID- 9541834
TI  - [Possibilities of preliminary treatment of infected soft tissue defects by vacuum
      sealing and PVA foam].
AB  - The vacuum sealing technique is a simple and cost-effective method in the
      treatment of traumatic and chronic soft-tissue defects. Wound cavities are filled
      with polyvinyl alcohol foam with embedded drainage tubes. The tubes are either
      drawn transcutaneously through the tissue, or placed epicutaneously, depending on
      the condition of the wound. The wound including the adjacent skin and the
      drainage tubes are covered by a transparent vapor transmitting polyurethane film.
      When the drainage tubes are connected with a vacuum bottle, negative pressure of
      60 to 80 kPa is established. The advantages of this vacuum sealing procedure are:
      protection against wound contamination, complete evacuation of wound fluids
      independent of gravity and rapid stimulation of dense, well vascularized
      granulation tissue. Relief of pain and early mobilisation improve the patients
      comfort. Between November 1994 and July 1996, 25 patients with 28 soft tissue
      defects underwent this procedure. Wound closure was performed in two cases with a
      free flap, in five cases by a loco-regional flap, in sixteen cases with mesh
      grafts, in three cases by secondary closure of the wound. Two cases were
      definitively treated with the vacuum sealing technique.

PMID- 9541835
TI  - [Treatment of fingertip defect injuries with a semi-occlusive dressing].
AB  - In the treatment of substance loss of fingertips it is crucial to maintain
      functional length and to restore adequate sensibility. By treating those injuries
      with a semiocclusive dressing according to Mennen and Wiese (1993), we were able
      to achieve both goals with excellent results, avoiding the necessity of local or
      regional flaps as well as shortening of bone to achieve primary closure. 82
      patients with 85 injured digits were treated either conventionally (primary
      closure with or without shortening of bone, vaseline gauze dressings: 31 digits)
      or with semiocclusive dressings (54 digits). 42 digits of the latter group with
      complete protocols were evaluated at the end of treatment. 26 digits with defects
      of skin and subcutaneous tissue of less than 1 cm2 to more than 2 cm2
      necessitated an average of 18 days until complete healing (minimum 6, maximum 46
      days). Eight digits with loss of skin, subcutaneous tissues and nailbed healed
      within 10 to 32 days (average 22 days) and eight digits in which defects included
      bone loss averaged 49 days for complete healing (37 to 64 days). No
      complications, especially no infections have been observed. All healed finger
      tips were well padded, painless, many without visible scar and with static two
      point discrimination between 2 and 8 mm.

PMID- 9541836
TI  - [Primary shortening--secondary lengthening. A new treatment concept for
      reconstruction of extensive soft tissue and bone injuries after 3rd degree open
      fracture and amputation of the lower leg].
AB  - The main problem in major limb replantation--especially of the lower extremity-
      is an extensive bone- and soft-tissue loss. The traditional replantation concept
      tries to preserve the initial limb length; only a small shortening is accepted.
      To avoid a more extensive shortening, often insufficient debridement at the time
      of replantation is carried out. After successful revascularisation, bone and soft
      tissue defects will be reconstructed according to the principles of staged
      reconstruction. Especially segmental nerve defects of more than one major
      peripheral nerve and severe skin and muscle loss necessitate extensive secondary
      grafting procedures. This often leads to a prolonged hospitalisation and a high
      complication rate. In 1951, Lorenz Bohler described the deliberate extremity
      shortening as a method of therapy in segmental combined bone-soft-tissue defects
      of the extremities. No additional surgical procedure were necessary to treat the
      soft tissue defect. A functional but shortened extremity was the result. With
      Ilizarov's principle of callus distraction he proved in an extensive experimental
      and clinical study the possibility to lengthen extremities without functional
      damage up to 20 cm. A new reconstruction concept--"concept of primary shortening
      with secondary limb lengthening"--for the treatment of amputation and/or
      amputation-like injuries was created by combining both principles mentioned
      above. At the time of replantation (reconstruction), deliberate shortening is
      carried out in order to reduce soft-tissue and/or bone defect or to enable
      primary nerve repair. Moreover, the aggressive debridement leads to a reduction
      of the local complication risk (wound healing disturbance, infection) and the
      potential systemic complications (crush-syndrome, ischemia-reperfusion-syndrome)
      after revascularisation of a large tissue bloc. Six to twelve months after
      replantation, secondary limb lengthening is started using an external or internal
      (= programmable intramedullary nail) distraction device. Since 1985, twelve
      patients (six macroamputations and six third-degree open fractures of the lower
      leg) have been treated using the "concept of primary shortening with secondary
      limb lengthening". Indications, operative technique, and results are shown and
      discussed, comparing this new concept to the traditional "concept of staged
      length-reconstruction" with extensive free tissue reconstruction and secondary
      nerve grafting.

PMID- 9541837
TI  - [AO-classification of fractures of the hand bones].
AB  - The AO classification of fractures has gained worldwide acceptance regarding
      usefulness of typification, therapeutic consequences and assessment of results.
      Following these principles, we developed a classification draft for fractures of
      the hand, using an alphanumerical code.

PMID- 9541838
TI  - [Surgical treatment of scaphoid pseudarthrosis--long term outcome with the
      Herbert screws].
AB  - Between 1984 and 1993, 131 scaphoid nonunions were treated with iliac crest bone
      grafting and the Herbert-screw. 105 patients were followed between one and ten
      years with an average followup period of 4.5 years. Bony union was achieved in 93
      patients with improvement of range of motion and grip strength. In 14 patients
      with DISI-instability, the angulation deformity was incompletely corrected with
      an average reduction of the scapho-lunate angle of eleven degrees. Limited
      athritic changes at the radial styloid were noted in 58%, intercarpal in 25% of
      the patients. Most frequent reasons for persistent nonunion were technical
      problems with the Herbert-screw.

PMID- 9541839
TI  - [Initial experiences with interposition of a silicon sheet in reconstruction of
      the wrist joint].
AB  - We report about the possibility to improve the condition of incongruent joint
      surfaces by temporary interposition of silicon sheet in the radiocarpal joint.
      The implant was used in 18 patients with damaged joint surfaces, either for the
      primary operation or for revision. It was removed four to six weeks after having
      started physiotherapy. Our results show that this procedure can improve the
      condition of joint surfaces. Silicon-induced granulation tissue can even uprough
      parts of the joint surface and thus reduce chondral friction. We did not see any
      complications.

PMID- 9541840
TI  - [Comparative stability studies with the modified Stellbrink external fixator].
AB  - We replaced original Stellbrink-fixator clamps with adjustable horizontal and
      vertical clamps. Thus, smaller bone fragments can be fixed and there is a
      possibility to correct their position after application of the fixator. This
      study compared the primary stability of different constructions by defined
      flexibility loadings in four-point bending. Statistical evaluation was done by
      the student-t-test. When used as compression osteosynthesis, the original
      Stellbrink fixator is the most stable (100%), whereas the modified fixator
      reaches only 90% of the stability of the original. The better stability of the
      original Stellbrink fixator only becomes significant when the flexion becomes
      greater than 13 degrees. Used for distance osteosynthesis, the original
      Stellbrink fixator is significantly more stable. Clinical examples are presented.

PMID- 9541842
TI  - [Ambulatory coronary angiography and PTCA].

PMID- 9541844
TI  - Outpatient coronary angiography: indications, safety, and complication rates.
AB  - In the years since the introduction of outpatient cardiac catheterization and
      coronary angiography, the indications for the use of these procedures have
      expanded rapidly with advancements in surgical and endovascular procedures. The
      safety of outpatient coronary angiography has been well established, comparing
      very favorably with that of inpatient procedures. At present, a variety of
      different outpatient facilities exist. Catheterization laboratories may adjoin a
      hospital or be free-standing; the safety and success of procedures performed in
      mobile cardiac catheterization laboratories has also been described. There are a
      variety of access techniques for cardiac catheterization in use today, and there
      are many types and sizes of catheters available. Miniaturization of equipment has
      reduced complications and allowed early ambulation and discharge from outpatient
      laboratories. In addition, the development and refinement of catheters and
      techniques for achieving hemostasis may allow further reductions in patient stay
      and complications. The complication rates of outpatient cardiac catheterization
      and coronary angiography are, in fact, quite low--in some cases, lower
      complication rates are seen in the outpatient population than in the inpatient
      population. Although this is certainly related in part to the fact that
      outpatients generally have more stable disease, it is clear that careful
      equipment choices, proper technique, and adequate monitoring have contributed to
      the success of these important outpatient procedures.

PMID- 9541845
TI  - [Percutaneous suture of femoral artery access sites after diagnostic heart
      catheterization and or coronary intervention. Safety and effectiveness of a new
      arterial suture technic].
AB  - The safety and efficacy of a suture-based closure device designed to achieve
      hemostasis at the femoral access site post catheterization procedures was
      compared to manual compression in a 600 patients randomized trial (data available
      for 590 patients). The patients were randomized to percutaneous vascular surgery
      (PVS) or manual compression after diagnostic (401 patients) and interventional
      (189 patients) procedures. Two types of PVS devices were used delivering 1 or 2
      sutures at the arterial access site. The overall results as well as the results
      by procedure type demonstrated a significant reduction in time of hemostasis (7.8
      +/- 4.8 min vs 19.6 +/- 13.2 min, p < 0.01) and time to ambulation (4.5 +/- 6.5
      hours vs 17.8 +/- 5.0 hours, p < 0.01) with the use of the PVS device. The safety
      results showed no significant differences in the incidence of vascular
      complications (5.7% for PVS vs 11.3% for compression) in the overall population
      or in the interventional patients subset (8.4% for PVS vs 9.6% for compression).
      However, the PVS device demonstrated a significant reduction in the incidence of
      vascular complications post diagnostic catheterization procedures (4.4 for PVS vs
      12.1% for compression, p < 0.05). The incidence of vascular complications and the
      time of hemostasis was similar in an American multicenter study (STAND II).
      CONCLUSION: Percutaneous vascular surgery is a safe and effective method to
      achieve hemostasis post catheterization procedure providing faster hemostasis and
      ambulation without increasing the rate of complication.

PMID- 9541843
TI  - [Peripheral arterial complications after heart catheterization].
AB  - After diagnostic and interventional cardiac catheterization, local vascular
      complications at the arterial entry site must be expected. With respect to the
      method applied for catheterization and the puncture site, the type of
      complications may vary. With transfemoral approach a large variety of vascular
      complications have to be feared, mostly in the form of bleeding complications and
      hematomas, arterial dissections or occlusions, pseudoaneurysms and AV-fistulas.
      Each of these complications may have the potential for serious morbidity. When
      cardiac catheterization is performed via the arteries of the arm (either in the
      classical Sones technique by arterial cutdown to the brachial artery or by direct
      puncture of the brachial or radial artery) vascular occlusions will mostly occur
      as local vascular complications. These occlusions can often be managed
      conservatively or by a surgical procedure. The incidence of a vascular
      complication is mainly dependent on patient-related (sex, age, height, weight,
      arterial hypertension, diabetes, presence of peripheral vascular disease and
      compliance of the patient after withdrawal of the sheath) and procedure-related
      (arterial access site, diagnostic or interventional study, sheath size,
      periprocedural anticoagulation, duration of intra-arterial sheath placement,
      faulty puncture technique, operator skill) factors. In addition, the definition
      of a complication, the publication year of a certain study and the technique used
      for identification of complications seem to play a role for the reported
      incidence of peripheral vascular complications after cardiac catheterization.
      Currently, incidences of 0.1 to 2% for significant local vascular complications
      after diagnostic transfemoral catheterization are reported, after interventional
      transfemoral treatment 0.5 to 5% and after complex procedures using large sheath
      sizes with periprocedural anticoagulation (directional atherectomy, IABP, left
      heart assist, valvuloplasty) up to 14%. Following transbrachial and transradial
      catheterization, local vascular complications at the entry site amount to 1 to 3%
      after diagnostic and 1 to 5% after interventional procedures. Local vascular
      complications may be diminished by a cautious and sensitive puncture technique
      with additional care in patients at higher risk for vascular complications
      (females, prediagnosed peripheral vascular disease, mandatory anticoagulation,
      necessity for large sheaths). By using smaller sized catheters and an adequate,
      defensive anticoagulation regimen, the rate of arterial access site complications
      may be reduced. Proper methods for achievement of hemostasis as well as a close
      and careful observation after sheath withdrawal are required.

PMID- 9541846
TI  - [Optimal x-ray contrast media for ambulatory coronary angiography from the
      microcirculatory point of view].
AB  - PROBLEM: Side effects must be expected in 7 to 8% of cases, even when non-ionic
      radiocontrast agents are used. Contrast agent-induced microcirculatory
      disturbances constitute one potential cause under discussion. These disturbances
      may be caused by either the hyperviscosity or the hyperosmolality of the contrast
      agents. Within the framework of 3 comparative studies, the influence of viscosity
      and/or osmolality in intraarterial bolus injections on downstream
      microcirculation was tested in patients with coronary heart disease. Blood flow
      in the nailfold capillaries was recorded by intravital videomicroscopy and
      evaluated off-line, before and after randomized injection of 20 ml of each
      different radiocontrast agent into the Arteria auxillaries ipsilateral. Injection
      of 20 ml of a radiographic contrast agent into the Arteria auxillaries with a
      viscosity of 9.9 mPas and an osmolality of 770 mOsmol/kg H2O (Iopromid with 370
      mg iodine/ml) results in a significant reduction in mean erythrocyte velocity in
      the ipsilateral nailfold capillaries from 0.76 +/- 0.27 to 0.39 +/- 0.31 mm/s
      after 30 s (p = 0.0001), corresponding to a reduction of 51.3%, whereas
      electrolyte solution shows no influence. With one exception, all patients reacted
      with a pronounced reduction in perfusion following injection of the radiocontrast
      agent, 3 patients showed an extreme reaction with flow cessation in the
      capillaries, in 1 case lasting up to 2 minutes. Following injection of 20 ml of
      Iodixanol with 270 mg iodine/ml (5.8 mPas, 290 mOsmol/kg H2O) a significant
      reduction of mean erythrocyte velocity of 60.8% was recorded from 0.44 +/- 0.27
      mm/s to 0.17 +/- 0.09 mm/s only 10 s after the injection (p = 0.0001) lasting to
      the end of the observation period (6 minutes). Following injection of 20 ml of
      low-viscosity Iopentol with 150 mg iodine/ml and comparable osmolality (1.7 mPas,
      340 mOsmol/kg H2O) no change in erythrocyte velocity was recorded (p = 0.151).
      Following injection of 2 high-viscosity radiocontrast agents of varying
      osmolality, mean erythrocyte velocity is reduced significantly in the first 30 s,
      after which period the erythrocyte velocity gradually increases (ANOVA repeated
      measures, category "time": p < 0.0001). The time curve for the 2 radiocontrast
      agents do not, however, differ (ANOVA, category "agents x time": p = 0.9890).
      Perfusion of the nailfold capillaries depends significantly on the viscosity, but
      not the osmolality, of the radiocontrast agent injected in coronary heart disease
      patients. From a microcirculatory point of view, it would therefore make sense to
      use low-viscosity radiocontrast agents in outpatients to exclude the existing
      risk of an induced myocardial microcirculatory disturbance.

PMID- 9541849
TI  - [Ambulatory PTCA--a judicial consideration].
AB  - According to the German law it is legal that PTCA is performed by health service
      physicians at an outpatient standard and not only in hospitals. In legal terms as
      they are described in the social law code (SGB-V) we should not use any longer
      the words outpatient versus inpatient. In legal terms "outpatient" means all
      physicians working outside a hospital in their own practice. Instead of
      outpatient we should use the word "in private practice".

PMID- 9541850
TI  - [Integrated medical practice. Which models make sense?].

PMID- 9541847
TI  - Outpatient radiofrequency catheter ablation.
AB  - Outpatient radiofrequency catheter ablation has been shown to be safe and cost
      effective in the treatment of supraventricular tachycardias due to
      atrioventricular nodal reentrant tachycardia and atrioventricular reentry
      tachycardia. Complications secondary to vascular access are similar to those
      during outpatient cardiac catheterization procedures. Specific complications due
      to catheter manipulation and radiofrequency ablation include among others cardiac
      tamponade, AV block and proarrhythmia. Proper patient selection can help to
      prevent specific complications in outpatient ablations. Patients probably not
      suitable for outpatient procedures include the elderly as well as comorbid
      patients. Not all ablation procedures are suitable for the outpatient setting.
      Ablation procedures with an increased risk of AV block or proarrhythmia should
      not be performed on an outpatient basis. In order to effectively perform
      outpatient procedures a back up support with specially trained personnel is
      helpful. Radiofrequency ablations require considerable experience, therefore
      ablation procedures int he outpatient setting should be restricted to operators
      with adequate experience.

PMID- 9541848
TI  - [First annual report of practitioners of interventional cardiology in private
      practice in Germany. Results of procedures of left heart catheterization and
      coronary interventions in the year 1996].
AB  - The German Society for Cardiac Angiography and Interventions in Private Practice
      has started a registry of cardiac procedures since 1996 in order to establish a
      standard for performance. Although quality management for the cath lab makes
      sense and is also legally required, there is no generally recommended
      infrastructure for quality assurance existing in Germany at this time. Therefore,
      the German Society of Cardiologists in Private Practice (BNK) initiated a project
      in 1994 to develop a computer program for paperless documentation of diagnostic
      cardiac catheterizations and coronary interventions (PTCA) using a minimal data
      set. In 1996, 8 private associated groups participated in this project. The
      (anonymous) analysis of 10,316 diagnostic cardiac catheterizations and 2597 PTCA
      yielded the following results: In 95% of the patients, diagnostic cardiac
      catheterization was performed using the femoral and in 5% the brachial/radial
      approach. The mean volume of administered contrast medium was 164 +/- 138
      ml/patient. The mean LV-EF was greater than 50% in 58.4% of the patients and
      between 30% and 50% in 10.1%. Coronary artery disease was diagnosed in 69.6% of
      the patients and valvular/congenital heart disease in 8.5%. In 18.4% of the
      patients undergoing diagnostic cardiac catheterizations no significant heart
      disease was identified. Mortality in the cath lab as well as the rate of cerebral
      insults was 0.05%. In 22.9% and 19% of the patients PTCA and cardiac surgery
      respectively was recommended. In patients undergoing PTCA, stable angina was
      present in 74.4% and unstable angina in 13.1%. Of the total number of PTCA
      procedures, 5.8% were performed in the setting of acute myocardial infarction.
      The PTCA lesion success rate was 96%, the mean diameter stenosis was 81% pre and
      6% post-intervention. The mortality rate at 1 month post-PTCA was 0.4%, and
      myocardial infarction 1.0%. An acute occlusion occurred in 1.3% of the PTCA
      patients; 0.6% had to be transferred for emergency bypass surgery. None of the
      cath labs had on-site surgery. In comparison to other registries, our data show
      some similarities but also some different trends. Thus, our newly developed
      software proved to be reliable, fast and easy to use. Participating centers
      receive immediate feedback regarding their position within the whole group.

PMID- 9541851
TI  - Detection and analysis of tracers in experimental drowning.
AB  - In animal experiments, studies on the mechanisms involved in drowning were
      carried out using latex and gold tracers of defined size and concentration. The
      tracers were detectable by fluorescence microscopy (latex tracers) and by
      electron microscopy (gold tracers) in the lungs, kidneys and lymph nodes and were
      analysed further by X-ray microanalysis using a transmission scanning electron
      microscope. Tracers with small diameters were shown to penetrate intercellular
      gaps of the alveolar epithelium and the larger tracers were incorporated into the
      epithelial and endothelial cells by active pinocytotic mechanisms thus passing
      through the air-blood barrier. The detection and analysis of tracers in organs of
      the systemic circulation originating from the immersion fluid can assist in
      understanding the pathophysiology of drowning and in some selected cases, in
      making a more definitive diagnosis.

PMID- 9541852
TI  - Interpreting forensic DNA evidence on the basis of hypotheses testing.
AB  - Analysis of a mixed biological stain by means of highly polymorphic VNTR systems
      usually reveals a profile composed of multiple markers. If the victim and one or
      several suspects match the profile the evidential strength of the matches has to
      be very carefully analysed. It is shown that a treatment to evaluate mixed stains
      within the scope of a hypotheses testing approach yields a formula identical to
      one proposed recently by Weir und coauthors. A simple combinatorial proof of this
      formula is presented. Further, a special computational formula is derived for the
      cases where the formula of Weir turns out to be cumbersome.

PMID- 9541853
TI  - Location and frequency of polymorphic positions in the mtDNA control region of
      individuals from Germany.
AB  - In order to identify polymorphic positions and to determine their frequency in
      the human mitochondrial D-loop containing region, the mitochondrial DNA (mtDNA)
      control region of 200 unrelated individuals from Germany were amplified and
      directly sequenced. Sequence comparison led to the identification of 190
      mitochondrial lineages as defined by 202 variable positions. The most frequently
      occurring lineage comprised 5 individuals, whereas 186 types of D-loop sequences
      were observed in only one individual. Of the sequences studied 7% are not unique
      but show at least one counterpart with an identical haplotype. The majority (61%)
      of the control regions investigated showed between four and eight nucleotide
      positions deviating from the reference sequence. The maximum number of deviations
      observed in a single control region was 18. The majority of the variable
      positions in the D-loop region (88%) are located within three hypervariable
      regions. Sequence variations are caused by nucleotide substitutions, insertions
      or deletions. As compared to insertions and deletions, nucleotide substitutions
      make up the vast majority of the mutations (90%). We have predominantly found
      transitions (75%) and a significantly lower frequency of transversions (15%)
      whereas insertions (6%) as well as deletions (4%) are rather rare. Upon
      sequencing the mitochondrial control region from 200 German Caucasians the
      genetic diversity was estimated at 0.99. The probability of two randomly selected
      individuals from a population having identical mtDNA types is 0.6%.

PMID- 9541854
TI  - Fatal wounds to the thorax caused by gunshots from blank cartridges.
AB  - Lethal injuries of the thorax due to shots fired from blank cartridges calibre 8
      mm are reported in three cases. The muzzle of the weapon was in contact with the
      left side of the breast (contact discharge) and injuries to bones were absent in
      all three cases. In two of the cases the pericardium was not involved but the
      anterior wall of the right heart ventricle was ruptured and death was due to
      cardiac tamponade. In the third case the pericardial sac and the left ventricle
      were both ruptured and the victim died due to rapid exsanguination. The cases
      demonstrate that the gas pressure from the exploding propellent of blank
      ammunition can be powerful enough to penetrate the thoracic wall.

PMID- 9541855
TI  - Codeine testing in sweat and saliva with the Drugwipe.
AB  - With the growing interest in drug testing within different sectors of society,
      there has become a need for drug assays that can be performed immediately at the
      site of specimen collection. Recently, Securetec (Ottobrunn, Germany) has
      introduced the Drugwipe, a non instrument-based, on-site immunodiagnostic assay
      for the detection of drugs on surfaces. Different tests are available for
      opiates, cocaine and cannabis. To document the applications of the Drugwipe
      "opiate" on human biological fluids, 60 mg codeine phosphate were orally
      administered to 6 subjects. First, sweat testing with the Drugwipe was studied.
      The wiping section of the kit was used to swab the forehead of the subjects for
      10 s, at 1, 4, 9 and 24 h after codeine administration. At the same time, for
      each period, a sweat patch (Pharmchek, USA) was applied to the outer portion of
      the upper arm. Codeine was then quantified in the patch by GC/MS and the measured
      concentrations used as reference. In all subjects except one the Drugwipe tested
      positive for opiates, however with few false negative results. In the second part
      of the study, results of the Drugwipe were compared with those obtained by GC/MS
      for saliva. The tongue of the subjects was carefully wiped over a period 24 h,
      and at the same time a specimen of saliva collected. Although codeine could be
      detected using the Drugwipe, numerous false negative results were observed.
      Codeine tested positive by GC/MS but remained negative using the Drugwipe in
      several cases. This can be explained by a codeine concentration which was too low
      to show positive with the Drugwipe, interfering substances may be present in
      saliva or the sampling procedure is inadequate.

PMID- 9541856
TI  - Unusual explanation for the death of a car passenger.
AB  - After collision of a car with the left rearside against a steel mast the 19-year
      old front seat passenger was found comatose on the seat. CT imaging showed a
      depression fracture parietal on the left with an intracerebral haemorrhage on the
      opposite side. The cause of the injury was unknown to the surgeons at the time of
      operation. Despite neurosurgical intervention the patient died 24 h after the
      accident. The post-mortem showed an additional depression fracture at the base of
      the skull in the right temporal region arousing suspicion of an impalement
      injury. Only inspection of the car by the forensic pathologists revealed the gas
      pressure telescopic shock absorber to be the cause of the head injury.

PMID- 9541857
TI  - Non-lethal penetrating cardiac injury from a crossbow bolt.
AB  - Crossbow injuries to the thorax are nowadays uncommon. The type of arrowhead used
      determines not only the form of entrance wound but often the outcome of these
      injuries. We report the case of a 38-year-old man who attempted to commit suicide
      by firing a bolt from a sport crossbow into his heart. Although the bolt
      penetrated the mediastinum causing a deep intraseptal myocardial lesion and the
      pre-operative diagnostic procedure delayed the necessary operation, the patient
      survived.

PMID- 9541859
TI  - Massive injury to the heart after attempted active compression-decompression
      cardiopulmonary resuscitation.
AB  - An 84-year-old woman was unsuccessfully resuscitated for 3 min using standard
      cardiopulmonary resuscitation (CPR), followed by 15 min of active compression
      decompression (ACD). The autopsy revealed that death was due to myocardial
      infarction complicated by rupture of the infarcted area and pericardial tamponade
      was diagnosed. Furthermore, a series of rib fractures, a transverse fracture of
      the sternum, rupture of the pericardial sac, the right ventricle, both atria and
      lacerations of the ascending aorta, were found with no signs of a vital reaction.
      To our knowledge, such extensive cardiac injury after CPR has not been previously
      reported. It is suggested that the pre-existing pericardial tamponade, the age of
      the patient and the application of the ACD-device to incorrect areas of the chest
      contributed to the extent of the cardiac injury. This case further adds to the
      suspicion of an increased risk of cardiac injuries when using an ACD device for
      cardiac massage.

PMID- 9541858
TI  - Intravenous injection of India ink with suicidal intent.
AB  - We describe the case of a 33-year-old man who injected 4 ml of India ink into one
      of the median cubital veins with suicidal intent. He was hospitalized in good
      general condition 10 h after the injection. Abnormal laboratory test results were
      a leukocytosis, an oximetrically determined methemoglobin level of 36.9% (normal
      range: 1.5%) and a free hemoglobin level of 74 mumol/L (normal range: < 25
      mumol/L). Toxicological examination showed the presence of nitrobenzene in blood
      and urine. Intravenous administration of vitamin C and tolonium chloride plus
      forced diuresis led to an improvement in cyanosis and a fall in the methemoglobin
      concentration. Repeated increase in the concentration of aminobenzene were
      successfully treated by hemodialysis with a high-flux dialyzer.

PMID- 9541860
TI  - ACTBP2-nomenclature recommendations of GEDNAP.
AB  - A system of nomenclature is proposed for the complex STR system ACTBP2 (SE33) in
      order to facilitate data exchange between laboratories. The nomenclature conforms
      to the ISFH recommendations as far as it is possible for such complex systems. A
      blind trial was carried out between up to 20 laboratories to ascertain the
      reproducibility of the nomenclature under working conditions. The population
      studies carried out have established that there are minimal regional differences
      in the allele frequencies and that the system of nomenclature is robust.

PMID- 9541861
TI  - Data on the loci LDLR, GYPA, HBGG, D7S8 and GC in a south Polish population.
AB  - Allele and genotype frequencies were determined in a sample of 102 inhabitants
      from South Poland with a commercial PCR based typing kit. No deviations from
      Hardy-Weinberg expectations were found. The combined power of discrimination for
      the five loci was 0.994. The systems did not show any allelic association between
      loci. The polymarker set was validated as useful for paternity testing and
      individual identification in a Polish population.

PMID- 9541862
TI  - Fluorescence based co-amplification and automated detection of the STR loci
      HUMFIBRA and HUMD21S11 in a Hungarian Caucasian population sample.
AB  - Population data were generated for the STR systems HUMFIBRA and HUMD21S11 for a
      Hungarian Caucasian population sample residing in Baranya County, Hungary (127
      unrelated individuals). The loci were coamplified using a fluorescence based PCR
      method and were typed automatically. For both loci 12 different alleles could be
      found including some variants. No deviations from Hardy-Weinberg expectations
      were observed. Both loci proved to be highly discriminating and valuable
      polymorphisms for forensic analyses.

PMID- 9541863
TI  - Turkish population data on the short tandem repeat locus TPOX.
AB  - Allele and genotype frequencies were determined for the STR (short tandem repeat)
      locus TPOX in a random Turkish population sample of 200 individuals.

PMID- 9541864
TI  - A study on the short tandem repeat systems HumCD4, HumTH01 and HumFIBRA in
      population samples from Yemen and Egypt.
AB  - The short tandem repeat systems (STRs) HumCD4 (CD4), HumTH01 (TH01) and HumFIBRA
      (FGA) were amplified by the polymerase chain reaction (PCR) on blood samples from
      100 unrelated Yemenians and 100 unrelated Egyptians. PCR products were separated
      on native horizontal discontinuous gel electrophoresis followed by silver
      staining. The distribution of observed phenotypes did not deviate from Hardy
      Weinberg equilibrium. While significant differences between both Arab populations
      and an European population from Austria were found at all loci, differences
      between the Egyptian and the Yemenian samples were found only for CD4. In a
      number of verified Austrian families (TH01: 426 meioses, CD4: 275 meioses, FGA:
      144 meioses) no mutations were found. The observation of a TH01 allele consisting
      of 4 repeats was confirmed by sequencing. Moreover we report the structure of a
      TH01 allele 6.3 observed in a Hungarian Caucasian population.

PMID- 9541865
TI  - Prolonged in vitro culture modifies the surface lipid composition of murine
      melanoma cell lines.
AB  - Lipid composition of two murine melanoma cell variants (B16, without malignant
      properties and B16-F10, with high metastatic activity), has been examined at
      different stages of growth. The aim of the work was to identify cell surface
      modifications due to the time length of in vitro culture, that could be one
      variable to consider when metastatic potential is studied. Some of the analyzed
      parameters (ganglioside- and glycoprotein-bound neuraminic acid, cholesterol,
      neutral glycolipids, phospholipids, triacylglycerols) undergo statistically
      significant variations at the various passages in B16-F10 line. Fatty acids
      composition of the phospholipidic fraction was changed only at the last observed
      passage (100) in B16 line. No one of the examined parameters justifies the
      ability of B16-F10 cells to invade distant districts and to originate new tumors.
      Probably detailed lipid analysis on cellular subfractions, as already performed
      in this study on total lipid extract of the whole cell, could be a valuable tool
      to identify differences related with metastatic potential.

PMID- 9541866
TI  - The effects of temperature and pH on the kinetics of reactions between catalase
      and its suicide substrate hydrogen peroxide.
AB  - Variation of initial (intact) activity (ai), inactivation rate constant (ki) and
      the partition ratio (r) of bovine liver catalase in the reaction with its suicide
      substrate, hydrogen peroxide, were determined in workable ranges of temperature
      (17-42 degrees C) or pH (5-10.5), using the data of progress curves. The changes
      of temperature had a slight effect on ai, giving a Q10 of 1.15 for the enzymatic
      breakdown of H2O2, corresponding to an improved value for its activation energy
      of 8.8 +/- l kJ.mol-1. In contrast, the ki was greatly increased by elevation of
      temperature, giving a Q10 of 2.1 for the suicide inactivation reaction of
      catalase. Consequently, a significant decrease of r was observed by increasing of
      temperature. In pH studies, decreasing of pH from 7.0 to 5.0 led to reduction of
      ai whereas the ki value was not effected significantly, possibly due to the
      parallel changes in affinities to free catalase and compound I for H2O2.
      Reduction of ki and alpha i were observed at pH > 9.5, where reversible
      dissociation of tetrameric enzyme into catalytically inactive subunits is
      possible. The r had a maximum value at pH around 7.5, similar to that of catalase
      activity. The effect of ionic strength on the above kinetic parameters was
      studied. There was not an observable influence when the ammonium sulfate
      concentration was below l M.

PMID- 9541867
TI  - Faster multipoint linkage analysis using Fourier transforms.
AB  - Genetic linkage analysis of human pedigrees using many linked markers
      simultaneously is a difficult computational problem. We have previously described
      an approach to this problem that uses hidden Markov models (HMMs) and is quite
      efficient for pedigrees of moderate size. Here, we describe a new, faster
      algorithm for the key step in the HMM calculation. The algorithm employs a fast
      Fourier transform on the group of pedigree inheritance patterns. It substantially
      improves the overall performance of the software package GENEHUNTER for
      performing linkage analysis. The Fourier representation opens up new research
      directions for pedigree analysis.

PMID- 9541868
TI  - Approximation algorithms for a genetic diagnostics problem.
AB  - We define and study a combinatorial problem called WEIGHTED DIAGNOSTIC COVER
      (WDC) that models the use of a laboratory technique called genotyping in the
      diagnosis of an important class of chromosomal aberrations. An optimal solution
      to WDC would enable us to define a genetic assay that maximizes the diagnostic
      power for a specified cost of laboratory work. We develop approximation
      algorithms for WDC by making use of the well-known problem SET COVER for which
      the greedy heuristic has been extensively studied. We prove worst-case
      performance bounds on the greedy heuristic for WDC and for another heuristic we
      call directional greedy. We implemented both heuristics. We also implemented a
      local search heuristic that takes the solutions obtained by greedy and dir-greedy
      and applies swaps until they are locally optimal. We report their performance on
      a real data set that is representative of the options that a clinical geneticist
      faces for the real diagnostic problem. Many open problems related to WDC remain,
      both of theoretical interest and practical importance.

PMID- 9541869
TI  - Protein folding in the hydrophobic-hydrophilic (HP) model is NP-complete.
AB  - One of the simplest and most popular biophysical models of protein folding is the
      hydrophobic-hydrophilic (HP) model. The HP model abstracts the hydrophobic
      interaction in protein folding by labeling the amino acids as hydrophobic (H for
      nonpolar) or hydrophilic (P for polar). Chains of amino acids are configured as
      self-avoiding walks on the 3D cubic lattice, where an optimal conformation
      maximizes the number of adjacencies between H's. In this paper, the protein
      folding problem under the HP model on the cubic lattice is shown to be NP
      complete. This means that the protein folding problem belongs to a large set of
      problems that are believed to be computationally intractable.

PMID- 9541870
TI  - Pairwise and multiple identification of three-dimensional common substructures in
      proteins.
AB  - In this paper, we present an algorithm to find three-dimensional substructures
      common to two or more molecules. The basic algorithm is devoted to pairwise
      structural comparison. Given two sets of atomic coordinates, it finds the largest
      subsets of atoms which are "similar" in the sense that all internal distances are
      approximately conserved. The basic idea of the algorithm is to recursively build
      subsets of increasing sizes, combining two sets of size k to build a set of size
      k + 1. The algorithm can be used "as is" for small molecules or local parts of
      proteins (about 30 atoms). When a high number of atoms is involved, we use a two
      step procedure. First we look for common "local" fragments by using the previous
      algorithm, and then we gather these fragments by using a Branch and Bound
      technique. We also extend the basic algorithm to perform multiple comparisons, by
      using one of the structures as a reference point (pivot) to which all other
      structures are compared. The solution is the largest subsets of atoms common to
      the pivot and at least q other structures. Although both algorithms are
      theoretically exponential in the number of atoms, experiments performed on
      biological data and using realistic parameters show that the solution is obtained
      within a few minutes. Finally, an application to the determination of the
      structural core of seven globins is presented.

PMID- 9541871
TI  - Statistical modelling and phylogenetic analysis of a deaminase domain.
AB  - Deamination reactions are catalyzed by a variety of enzymes including those
      involved in nucleoside/nucleotide metabolism and cytosine to uracil (C-->U) and
      adenosine to inosine (A-->I) mRNA editing. The active site of the deaminase (DM)
      domain in these enzymes contains a conserved histidine (or rarely cysteine), two
      cysteines and a glutamate proposed to act as a proton shuttle during deamination.
      Here, a statistical model, a hidden Markov model (HMM), of the DM domain has been
      created which identifies currently known DM domains and suggests new DM domains
      in viral, bacterial and eucaryotic proteins. However, no DM domains were
      identified in the currently predicted proteins from the archaeon Methanococcus
      jannaschii and possible causes for, and a potential means to ameliorate this
      situation are discussed. In some of the newly identified DM domains, the
      glutamate is changed to a residue that could not function as a proton shuttle and
      in one instance (Mus musculus spermatid protein TENR) the cysteines are also
      changed to lysine and serine. These may be non-competent DM domains able to bind
      but not act upon their substrate. Phylogenetic analysis using an HMM-generated
      alignment of DM domains reveals three branches with clear substructure in each
      branch. The results suggest DM domains that are candidates for yeast,
      platyhelminth, plant and mammalian C-->U and A-->I mRNA editing enzymes. Some
      bacterial and eucaryotic DM domains form distinct branches in the phylogenetic
      tree suggesting the existence of common, novel substrates.

PMID- 9541872
TI  - Modelling and simulation of motility in actomyosin systems.
AB  - We present a model mechanism for simulating the diffusive motion and fluctuations
      inherent in myofibrillar sarcomere and its subunits at the molecular level. The
      model couples Langevin dynamics with Huxley kinetics to reproduce the transient
      patterns of momentum transfer, force generation and resulting motility due to the
      interactive activities of actin and myosin crossbridges. When myosin is detached
      from actin, our model predicts Brownian displacements centered at 0 +/- 8 nm
      (mean +/- SD, n = 265,308) and it is broadly distributed due to the Brownian
      noise. Attachment events produced displacements with step sizes of approximately
      8 +/- 6 nm (mean +/- SD, n = 34,693), which is in agreement with some recent
      optical-tweezers transducer experimental results. The proposed model could form
      the basis for a complete qualitative and quantitative description of the evolving
      complex interactions of the molecular proteins--actin and myosin--in the overall
      framework of muscular contraction studies.

PMID- 9541873
TI  - On the distribution of k-tuple matches for sequence homology: a constant time
      exact calculation of the variance.
AB  - We study the distribution of a statistic useful in calculating the significance
      of the number of k-tuple matches detected in biological sequence homology
      algorithms. The statistic is Rn,k, the total number of heads in head runs of
      length k or more in a sequence of iid Bernoulli trials of length n. Calculation
      of the mean is straightforward. Poisson approximation formulas have been used for
      the variance because they are simple and powerful. Unfortunately, when p =
      P(Head) is large, the Poisson approximation no longer works well. In our
      application, p is large, say .75, and we have turned instead to direct
      calculation of the variance. Surprisingly, we are able to show that the variance,
      which is based on the interactions of O(n2) random variables, can be computed in
      constant time, independent of the length of the sequence and probability p. This
      result can be used to calculate the mean and variance of a number of other head
      run statistics in constant time. Additionally, we show how to extend the result
      to sequences generated by a stationary Markov process where the variance can be
      calculated in O(n) time.

PMID- 9541874
TI  - Expectation and variance of true and false fragment matches in DNA restriction
      mapping.
AB  - Consider a DNA mapping project in which overlap of clones is inferred from
      multiple complete restriction enzyme digests. Each enzyme cuts each clone
      randomly into fragments whose lengths are determined with some error. Clones that
      share fragments with matching lengths could contain a region of overlap. However,
      common fragment lengths may be due to random coincidence leading to a false
      overlap declaration. Although the probability of false fragment matching is
      small, a mapping project involves a large number of clone comparisons.
      Consequently, erroneous fragment matches can be a serious problem. We use a
      geometrical probability approach to develop exact integral formulas and first
      order approximations for the expected number and variance of classes of fragment
      pairs that will be identified falsely as matching. We also find exact formulas
      for the expected value, and variance of the number of true fragment matches.
      These formulas are useful in comparing different mapping strategies.

PMID- 9541875
TI  - Optimization of restriction fragment DNA mapping.
AB  - Consider a mapping project in which overlap of clonal segments is inferred from
      complete multiple restriction digests. The fragment sizes of the clones are
      measured with some error, potentially leading to a map with erroneous links. The
      number of errors in the map depends on the number and types of enzymes used to
      characterize the clones. The most critical parameter is the decision rule k, or
      the criterion for declaring clone overlap. Small changes in k may cause an order
      of magnitude change in the amount of work it takes to build a map of given
      completion. We observe that the cost of an optimal mapping strategy is
      approximately proportional to the target size. While this finding is encouraging,
      considerable effort is nonetheless required: for large-scale sequencing projects
      with up-front mapping, mapping will be a non-negligible fraction of the total
      sequencing cost.

PMID- 9541876
TI  - Constructing additive trees when the error is small.
AB  - We consider the problem of constructing an additive tree from a given matrix of
      pairwise distances, when observation errors are allowed. We give conditions under
      which the tree topology is unique and semi-unique. We also design an efficient
      algorithm to construct a tree when the error is relatively small.

PMID- 9541877
TI  - Duplication-based measures of difference between gene and species trees.
AB  - In the framework of a duplication-based method for comparing gene and species
      trees, the concepts of "duplication" and "loss" are reformulated in set-theoretic
      terms. A number of related tree dissimilarity measures is suggested, and
      relations between them are analyzed. For any node in the species tree, the number
      of gene duplications for which it is a "non-child" loss coincides with the number
      of times when the node's parent is an intermediate between the mapping images of
      a gene node and its parent. This implies that the total number of losses is equal
      to the number of intermediate nodes plus the number of one-side duplications and,
      thus, provides an alternative proof for a conjecture made by Mirkin, Muchnik, and
      Smith (1995). Another formula proven involves crossings (incompatible gene
      species node pairs): the number of losses equals the number of crossings plus the
      number of duplications.

PMID- 9541878
TI  - Evolution of DNA or amino acid sequences with dependent sites.
AB  - A framework is outlined to study the evolution of DNA or amino acid sequences, if
      sequence sites do not evolve independently. The units of evolution are
      nonoverlapping subsequences of length l. Each subsequence evolves independently
      of the others, but within a subsequence the sequences show a Markov order one
      dependency. We describe an algorithm to mimic the evolution of such sequences.
      The influence of dependencies between sites on distance estimates and the
      reliability of tree reconstruction methods is investigated. We show that an
      inappropriate model of sequence evolution in the tree reconstruction process will
      lead to a nonempty Felsenstein zone. Finally, we describe a method to infer l
      from sequence data. Examples from the evolution of DNA sequences as well as from
      amino acids are given.

PMID- 9541879
TI  - Multistage sequencing by hybridization.
AB  - The sequencing of DNA is an important and difficult problem. Many interesting
      algorithms combine various technologies in an attempt to sequence long regions of
      DNA. One such algorithm is sequencing by hybridization (SBH). We briefly review
      SBH and mention the drawbacks that prevent it from being used in practice. We
      then present a theoretical algorithm that uniquely determines a sequence of
      length n through hybridization experiments that require the examination of only
      O(n2log(n)) subsequences. The key idea is to double subsequence length in each
      iteration of the algorithm. There are various problems associated with
      transforming the theoretical algorithm into a practical biological procedure.
      However, the general strategy of increasing subsequence length may be used to
      develop algorithms that are feasible given the current state of technology.
      Combining this strategy with a computer processing phase leads to a novel method
      of extending the resolving power of standard SBH techniques.

PMID- 9541880
TI  - An upper body exercise system incorporating resistive exercise and neuromuscular
      electrical stimulation (NMS).
AB  - A device is described which combines arm crank ergometry and neuromuscular
      electrical stimulation (NMS) delivered at different phases of the crank cycle.
      Details of the device including circuit schematics are shown. The device was
      evaluated by non-paralyzed subjects for its operational safety and by tetraplegic
      subjects for its effectiveness as a muscle-strengthening tool. All subjects
      showed improvement in one or more of their manual muscle scores. The most
      dramatic increased motor score occurred in the triceps muscle group. There was an
      average increase in the manual muscle score of 1.1 +/- 0.2 for the left triceps
      and 0.7 +/- 0.1 for the right triceps after eight weeks of NMS assisted exercise.
      No adverse effects were experienced and it appears to meet safety considerations
      necessary for this group of individuals. Preliminary observations indicate that
      an eight-week exercise protocol that utilizes this device can be beneficial for
      this population.

PMID- 9541881
TI  - Home monitoring of bladder pressure and volume in individuals with spinal cord
      injury and multiple sclerosis.
AB  - Individuals with spinal cord injury and multiple sclerosis are at high risk for
      developing kidney dysfunction due to high bladder pressures. We have developed a
      device for frequent monitoring of bladder pressures at home in those patients who
      use intermittent catheterization to empty their bladders. Of eight subjects
      enrolled in the study, only five conducted home recording of pressure. Vesical
      and abdominal pressures measured at home were significantly lower than clinical
      cystometric pressures. However, subtracted detrusor pressures obtained from home
      records and cystometric records were not significantly different. The home
      detrusor pressures were consistent over a large time and volume range. Therefore,
      the home monitoring method could be used to establish a normal range of bladder
      pressures at home and to rapidly identify high bladder pressures in advance of
      upper urinary tract deterioration.

PMID- 9541882
TI  - The impact of urodynamic parameters on the upper tracts of spinal cord injured
      men who void reflexly.
AB  - Few studies have evaluated which urodynamic parameters impact the upper urinary
      tracts in men with complete spinal cord injuries (SCI) who void reflexly.
      Previous studies focused primarily on voiding pressures. This study investigated
      the effects of bladder wall compliance, opening pressure, maximum detrusor
      voiding pressure, duration of the uninhibited contraction, cystometric bladder
      capacity and post-void residual on vesicoureteral reflux and stasis of the upper
      tracts. Urodynamic studies, cystograms and renal scans of 84 consecutive men with
      complete SCI who void reflexly were evaluated. Of the 84 patients (168 renal
      units), 71 men (142 renal units) had normal upper tracts, four patients (four
      renal units) had vesicoureteral reflux and nine patients (15 renal units--12
      bilateral, three unilateral) had upper urinary tract stasis. There was no
      statistical difference between those with reflux and those without reflux with
      regards to any urodynamic parameter evaluated. When comparing those with and
      without upper urinary tract stasis, the only statistically significant difference
      in urodynamic parameters was the duration of bladder contraction. The mean
      duration of the uninhibited contraction in the non-stasis group was 113.7 seconds
      +/- 84 seconds (1.9 minutes +/- 1.4 minutes). The mean duration of the
      uninhibited contraction in the stasis group was 236.4 seconds +/- 139.1 seconds
      (3.9 minutes +/- 2.3 minutes, p = 0.0098). In summary, the duration of bladder
      contraction, which reflects both detrusor and sphincter function, was found to be
      an important variable in those with upper tract stasis. This should be considered
      when evaluating and treating men with complete SCI who void reflexly.

PMID- 9541883
TI  - Bowel care for individuals with spinal cord injury: comparison of four
      approaches.
AB  - The efficacies of four bowel care regimens (bisacodyl suppositories, glycerin
      suppositories, mineral oil enemas and docusate sodium mini-enemas) were compared
      in seven subjects with traumatic spinal cord injury. Efficacy was assessed in
      terms of colonic transit time, bowel evacuation time and subjective responses to
      a questionnaire. Both docusate sodium mini-enemas and mineral oil enemas
      decreased total and left-sided colonic transit time. However, docusate sodium
      mini-enemas were superior to mineral oil enemas in terms of the decrease in bowel
      evacuation time and symptom reduction. Results in this small group of subjects
      suggest that docusate sodium mini-enemas may have advantages in the management of
      bowel evacuation in individuals with spinal cord injury.

PMID- 9541884
TI  - Viral hepatitis in patients with spinal cord injury is explained by known risk
      factors.
AB  - Spinal cord injury (SCI) has been reported to be associated with viral hepatitis.
      However, this association may be related to other confounding factors, such as
      intravenous drug abuse or blood transfusions. Screening for viral hepatitis
      associated risk factors and serum serologies, including HBsAg, anti-HBc, anti-HBs
      and anti-HCV testing, were performed in 78 randomly selected SCI patients and 93
      non-alcoholic patients attending a general medical clinic. Hepatitis B and C
      seropositivies in SCI patients were 29.5 percent and 14.1 percent, respectively,
      and were significantly associated with a history of intravenous drug abuse. In
      contrast, hepatitis B and C seropositivities in non-alcoholic general medicine
      clinic patients were 22.6 percent and 2.2 percent, respectively. In the subgroup
      of patients without known viral hepatitis risk factors, there were no significant
      differences between SCI and non-alcoholic patients with respect to hepatitis B
      (21.4 percent vs. 22.1 percent) or hepatitis C (0 percent vs. 1.3 percent)
      seropositivity. Stepwise logistic regression also failed to detect an association
      of SCI with viral hepatitis. In conclusion, the increased seroprevalence of
      hepatitis C in SCI patients is secondary to intravenous drug use and blood
      transfusions. Further preventive measures such as improved hepatitis screening of
      blood donors and substance abuse treatment should decrease viral hepatitis
      exposure in SCI patients.

PMID- 9541885
TI  - Comparison of rehabilitation outcomes in violent versus non-violent traumatic
      SCI.
AB  - This paper represents the results of a cohort study comparing functional outcomes
      of individuals with violent and non-violent traumatic spinal cord injury (SCI)
      following inpatient rehabilitation. Twenty-seven consecutive patients with a
      diagnosis of traumatic SCI of violent etiology (gunshot wound, stabbing or
      assault) and 27 patients with non-violent etiology (motor vehicle accident and
      falls) were matched for neurological level of injury and classification.
      Demographic comparison of violent versus non-violent groups revealed mean age 30
      versus 39, gender 93 percent versus 78 percent male, race 89 percent versus 59
      percent non-white, 74 percent versus 41 percent unmarried and 56 percent versus
      22 percent unemployed, respectively. Violent and non-violent traumatic SCI groups
      had similar lengths of stay, admission and discharge functional independent
      measures (FIM), FIM improvement, payor sources, hospital charges and discharge to
      home rates. Despite the differences noted in the demographics of violent and non
      violent traumatic SCI, these two matched groups achieved similar functional
      outcomes and discharge disposition following inpatient rehabilitation.

PMID- 9541887
TI  - [Ophthalmic surgery with local anesthesia or intubation anesthesia at the Leipzig
      University Ophthalmology Clinic].
AB  - BACKGROUND: Different opinions about the reliability and serious complications
      after regional anesthesia have been reported. The paper describes our experiences
      in deciding about regional or general anesthesia for ophthalmic surgery. PATIENTS
      AND METHODS: For this report we analyzed retrospectively our protocols of all
      operations performed in 1995. Eight categories of procedures were developed to
      give an insight in our way of decision for local or general anesthesia. We
      imagine the applied technique of peribulbaranesthesia. RESULTS: 3184 patients
      were operated on in 1995, in the regional anesthesia group the age ranges from 17
      to 96 years, in the general anesthesia group from 3 months to 85 years. In 69.9%
      of all patients we performed a local anesthesia and in 30.1% we chose general
      anesthesia. The spread of cases and the surgical procedure corresponding to one
      of these eight classes below are described in this survey. CONCLUSIONS: Almost
      70% of our patients who underwent an ophthalmosurgical procedure were operated on
      under regional anesthesia. No serious complications have occurred and no
      procedure had do be stopped off due to an insufficient analgesia or akinesia. We
      demonstrate some observations concerning the duration of pain after the injection
      and our indications for general anesthesia in ophthalmic surgery.

PMID- 9541886
TI  - [Vision disorders in the elderly].
AB  - BACKGROUND: British trials from the 60's reveal that older patients tend to
      underreport their health problems. They misjudge them as non specific or being
      caused by old age. In this study we investigate whether standard preventive
      assessment facilitates the detection and early intervention of ophthalmological
      problems in old age. METHODOLOGY: For the first time a representative screening
      trial for older patients visiting their general practitioner was carried out in
      Germany, 1994. The surgeries as well as the 466 participating patients over 69
      years were randomly selected. GPs were asked to examine the visual problems of
      the participants per standardized questionnaire and visual accuracy test. GPs had
      to report uncovered problems and planned interventions. RESULTS: Altogether, 75%
      of the participating patients had some need for a further ophthalmological
      diagnostic or therapeutic intervention. Every fourth patient had not seen an
      ophthalmologist within the last two years. 40% of the participants complained of
      eye problems. 22% had symptoms of a glaucoma. Visual accuracy was low in 17% of
      the older patients. General practitioners had only been aware of 50% of all
      visual problems requiring further intervention. About half of the patients with a
      low visual accuracy and 70% with an indication of glaucoma had been unknown
      before. For about half of the patients requiring ophthalmological investigation
      (excluding problems with glasses) an intervention was planned. For every fifth,
      the general practitioners initiated referrals. CONCLUSION: The standard
      preventive facilitated to detect a high rate of visual problems in old age. Close
      cooperation with ophthalmologists is necessary for patients who do not take up
      the specialists' eye check ups (especially those at risk). Patients with severe
      eye problems in some cases in spite of specialists' care also require
      interdisciplinary treatment.

PMID- 9541888
TI  - [Latanoprost--a new prostaglandin F2 alpha analog in therapy of glaucoma--an
      overview].
AB  - An ideal glaucoma drug reduces intraocular pressure profoundly and long-lastingly
      without known major side effects. Latanoprost, a new prostaglandin F2 alpha
      analogue, indeed has these properties. However, we need long-term experience to
      exclude major, clinically relevant side effects. The influence of latanoprost on
      ocular circulation also needs further evaluation. Nevertheless, the clinician
      does have a new and very potent drug to reduce intraocular pressure. Literature
      search by Medline.

PMID- 9541889
TI  - [Cataract surgery in nanophthalmic eyes with an axial length of less than 20.5
      mm].
AB  - BACKGROUND: Aim of this study was to analyze the results of cataract surgery in
      nanophthalmic eyes with axial length of less than 20.5 mm. PATIENTS AND METHODS:
      From 1991 to 1996 extracapsular cataract extraction with posterior chamber lens
      implantation was performed in 20 eyes of 19 patients (mean age 70.2 +/- 12.7
      years, 4 male, 16 female) with axial length of less than 20.5 mm. Mean
      preoperative visual acuity was 0.16 +/- 0.15, refractive error +5.1 +/- 3.8 dpt
      and intraocular pressure 18.7 +/- 10.3 mm Hg. The mean follow-up was 24.4 months.
      Patient data were collected prospectively with standardized "Erlanger
      Augenblatter" and the computer-aided automatized operation record system "OPERA".
      These data together with the biometrical data were analized in a retrolective
      manner. RESULTS: Preoperatively 6 of 20 eyes had angle closure situation, 7 of 20
      eyes had undergone intraocular surgery previously (5 x iridotomy, 1 x surgical
      iridectomy, 1 x filtration procedure). Pseudoexfoliation syndrome was present in
      3 eyes. The posterior chamber lens (mean refractive power 31.7 +/- 3.0 dpt, optic
      diameter 6.5 and 7.0 mm) was positioned 18 x intracapsular, 2 x into the sulcus
      and 1 x by scleral fixation due to capsular rupture without vitreous loss. In 16
      of 20 eyes iris surgery was performed additionally, in one eye an anterior
      sclerotomy was necessary. Intraoperatively "vis a tergo" occurred in 10 eyes and
      anterior chamber hemorrhage in one eye. Visual acuity improved in 16 of 20 eyes.
      The mean visual acuity was 0.3 +/- 0.2. At the end of follow-up 13 eyes had an
      improvement of visual acuity. Mean intraocular pressure was 16.5 +/- 3.3 mm Hg,
      refractive error was +0.47 +/- 2.9 dpt and differed by -0.49 +/- 1.8 dpt from the
      preoperatively calculated refraction. Postoperatively angle closure glaucoma
      developed in one eye, a ciliopseudophakic angle closure glaucoma and recurrent
      iris bombata in one eye. Reoperations included cyclokryokoagulation in two eyes,
      pars plana vitrectomy in one eye and repeated Nd-YAG iridotomies in one eye.
      CONCLUSION: Regarding the special anatomic situation, the surgical procedure has
      to be planned individually, including the determination of sclera thickness,
      corneal diameter and lens volume/eye volume ratio.

PMID- 9541890
TI  - [Intraocular pressure values in intubation anesthesia in patients with and
      without chronic open angle glaucoma].
AB  - BACKGROUND: A number of clinical studies have investigated the influence of
      hypnotics and relaxants on intraocular pressure. All of them referred to the
      normal eye. Our goal was to show if there is a difference in intraocular pressure
      profile during general anesthesia between eyes with and without primary open
      angle glaucoma. PATIENTS AND METHODS: We prospectively examined two groups of 20
      patients with and without primary open angle glaucoma. Intraocular pressure (IOP)
      readings were taken using a Perkins hand held applanation tonometer during
      routine surgery on cataract or glaucoma on the fellow eye. Balanced anesthesia
      was carried out using Etomidate, Vecuronium, Fentanyl, N2O and Enflurane.
      RESULTS: In the glaucoma group IOP fell from 20.3 +/- 4.1 mm Hg before induction
      of anesthesia (baseline) to 13.2 +/- 3.8 mm Hg (65% of baseline) after induction
      and 12.6 +/- 4.2 mm Hg (62%) 5 minutes after induction. In the non-glaucoma group
      IOP was 16.3 +/- 3.5, 9.7 +/- 3.0 (62%) und 9.6 +/- 3.0 (59%) respectively.
      Directly after placement of endotracheal tube we read 17.8 +/- 7.6 mm Hg (87%) in
      the glaucoma and 13.0 +/- 5.9 mm Hg (82%) in the non-glaucoma group. Shortly
      before removal of endotracheal tube we found IOP to be 21.3 +/- 4.5 mm Hg (107%)
      in the glaucoma and 17.8 +/- 6.8 mm Hg (106%) in the non-glaucoma group. Back on
      the ward we measured 19.8 +/- 4.1 mm Hg (94%) and 15.4 +/- 3.5 (93%)
      respectively. Pressure changes relative to baseline values show no statistically
      significant differences between the two groups. CONCLUSIONS: General anesthesia
      lowers IOP to the advantage of intraocular surgery. There is no statistically
      significant difference in pressure change relative to baseline value in eyes with
      and without primary open angle glaucoma.

PMID- 9541891
TI  - [Capsulotomy in intumescent cataract with the high frequency diathermy
      capsulotom].
AB  - BACKGROUND: Intumescent or hypermature cataracts sometimes mean a difficult
      capsulorhexis. High frequency capsulotomy represents a satisfying solution for
      this problem. PATIENTS AND METHODS: 26 patients with intumescent cataracts
      undergoing cataract surgery with high frequency capsulotomy were enclosed into
      this study. Clinical application of this technique was examined intraoperatively
      and postoperatively. RESULTS: Only in 4 patients out of 26 it was not possible to
      achieve a circular cut by capsulotomy. Residual bridges could be cut by scissors.
      CONCLUSIONS: High frequency capsulotomy means a convenient alternative to
      capsulorhexis, while correct technique intraoperatively is extremely important
      for satisfying clinical results.

PMID- 9541892
TI  - [Tyndallometry in patients with diabetic macular edema before and after central
      laser coagulation].
AB  - BACKGROUND: It is known that the breakdown of the blood-retina-barrier (BRB) as
      well as the blood-aqueous-barrier (BAB) is one of the earliest pathopysiological
      changes in the diabetic eye. Some previous studies confirmed a statistically
      significant increase of flare values of the aqueous humor in eyes with diabetic
      retinopathy which is lineary correlated with the protein concentration. This
      study investigated the effect of a central laser photocoagulation in eyes with
      clinically significant macular edema on the permeability of the blood-aqueous
      barrier (BAB). PATIENTS AND METHODS: We included 22 eyes of 22 patients with
      diabetes mellitus suffering from clinically significant macular edema determined
      by fluorescence angiography giving an indication for central laser treatment. Two
      measurements of aqueous flare were taken, the first before laser photocoagulation
      (grid with about 100 coagulations) and the second 6 to 8 weeks after treatment.
      RESULTS: The flare values before treatment were 11.4 +/- 4.1 phc/ms (4.9-23.8)
      and after treatment 10.0 +/- 3.5 phc/ms (5.7-16.7). There was a significant
      difference between both measurements (p = 0.039). CONCLUSIONS: The protein
      concentration of the aqeoues humor is a parameter which allows to characterize
      the permeability of the BAB. The central laser photocoagulation seems to seal the
      vessels.

PMID- 9541893
TI  - [No effect of diabetes mellitus on the morphology of the optic nerve papilla in
      primary open angle glaucoma].
AB  - PURPOSE: To evaluate the effect of diabetes mellitus on the optic disc morphology
      in primary open-angle glaucoma. PATIENTS AND METHODS: Within a group of 364
      patients with primary open-angle glaucoma, a subgroup of 52 patients with
      diabetes mellitus and a second subgroup of 312 patients without diabetes mellitus
      were compared with each other. Eyes with proliferative diabetic retinopathy had
      been excluded. Both subgroups were matched for age, gender, and refractive error.
      The optic disc was morphometrically evaluated using stereo disc photographs.
      RESULTS: The two subgroups did not vary significantly (p > 0.10) in mean size of
      the optic disc, neuroretinal rim and zones Alpha and Beta of the parapapillary
      chorioretinal atrophy, and frequencies of disc hemorrhages. CONCLUSIONS: Patients
      with or without diabetes mellitus do not differ significantly in the morphology
      of the optic disc. One may conclude that diabetes mellitus does not markedly
      influence planimetric assessed optic disc damage in patients with primary open
      angle glaucoma, if eyes with proliferative diabetic retinopathy have been
      excluded.

PMID- 9541894
TI  - [Objective assessment of visual field defects using multifocal
      electroretinography].
AB  - BACKGROUND: Multifocal electroretinography allows simultaneous recording of 61
      focal electroretinographic signals from the retina of the posterior pole. The
      function of the outer retinal layers can be mapped for a visual field of 30.5
      degrees radius. We herein describe the topography of such potentials in patients
      with hemianopic and concentric visual field defects. SUBJECTS AND METHODS: Six
      patients with visual field defects caused by chorioretinal and central visual
      pathways diseases were examined using multifocal ERG. RESULTS: In 30 normal
      volunteers in the entire 30 degrees visual field clear signals were obtained. In
      the patients with visual field defects caused by retinal diseases in areas with
      reduced light sensitivity diminished electroretinographical activity was found.
      In contrast, in patients with bitemporal hemianopsia due to a chiasmal lesion no
      correlation between visual field and magnitude of focal ERGs was seen.
      CONCLUSIONS: In retinal disorders defects in multifocal ERG presented the similar
      pattern as scotomata in perimetry. The patient with visual field defects due to
      disturbances in the chiasma exhibited a normal ERG-topography. In patients with
      visual field defects multifocal ERG supported differentiation of the location of
      the lesion.

PMID- 9541895
TI  - [Experimental results of erbium:YAG laser vitrectomy].
AB  - BACKGROUND: Vitrectomy performed by conventional guillotine devices includes the
      risk of mechanical damage to retina as well as other ocular structures. The
      present study aims to investigate the efficacy of the Er:YAG laser for vitreous
      liquefaction. MATERIALS AND METHODS: Vitreous liquefaction by means of Er:YAG
      laser pulses was performed using a special handpiece. The output of an Er:YAG
      laser operating at 2.94 microns was coupled into a ZrF optical fibre (length 2 m)
      which ended inside a cavity located at the quartz tip (diameter 320 microns) of
      the handpiece where tissue ablation took place. The viscosity of the liquefied
      vitreous was determined by rotation viscosimetry and compared to liquefied
      vitreous obtained by mechanical vitrectomy. In addition, the aspiration flow
      (ml/min) was correlated to the repetition/cutting rate of the laser and the
      cutter. The temperature rise at the handpiece was recorded with a micro
      thermocouple. RESULTS: The cutting threshold was determined to 5 mJ +/- 3 mJ at a
      pulse duration of 200 microseconds. The viscosity of the vitreous liquefied with
      the Er:YAG laser was 31 +/- 10 mPa s which is similar to the results of
      mechanical vitrectomy (42 +/- 19 mPa s) but significant less than that of normal
      vitreous (880 +/- 280 mPa s). The aspiration of the laser handpiece in dependence
      to the repetition rate increases linear up to 2.6 ml/min at 30 Hz. The
      temperature increase at the handpiece was < 1 K under vitrectomy conditions
      (aspiration and irrigation) with an averaged laser power of 0.3 W (10 mJ at 30
      Hz). CONCLUSIONS: The decreased vacuum forces used by the laser vitrectomy system
      may result in less mechanical stress to the retina as well as intravitreal
      structures which may be attached to it. An Er:YAG laser vitrectomy system may
      offer the potential of fewer complications during vitrectomy.

PMID- 9541896
TI  - [Listeria monocytogenes-induced endogenous endophthalmitis in an otherwise
      healthy patient: PCR-assisted rapid diagnosis as the basis for successful
      therapy].
AB  - BACKGROUND: Listeria monocytogenes is a rare cause of endogenous endophthalmitis.
      Only 14 cases are published in the literature so far. All eyes showed similar
      clinical features and profound visual loss. PATIENTS AND METHODS: We report on a
      case of an otherwise healthy 73-year-old male. He was referred to our hospital
      because of acute hypopyoniritis with secondary glaucoma. Within a few hours the
      severity of the intraocular infection increased dramatically resulting in the
      clinical picture of an acute endophthalmitis. RESULTS AND CONCLUSION: Early
      identification of the causative pathogen in the aqueous humor after anterior
      chamber paracenthesis using polymerase chain reaction (PCR) and the initiation of
      a specific, systemic antibiotic medication resulted in a complete recovery of
      visual acuity.

PMID- 9541897
TI  - [Manifestation of Wegener's granulomatosis as lacrimal sac tumor].
AB  - HISTORY AND SIGNS: This is a report on a patient, who presented an ulcerated
      lesion (1.5 x 1.2 cm) in the lacrimal sac area. The lesion had existed for 3
      months before the patient went to an ophthalmologist. The lacrimal pathway was
      rinsable all the time. THERAPY AND OUTCOME: The patient was treated by
      antibiotics and leukase cones at first. But the lesion showed no tendency to heal
      under this therapy. The patient was sent to the ETN department for further
      investigations. At this time the suspicion of a malignant process was discussed.
      In the meantime the lesion became epithelialized, but no closure could be reached
      at any time. The CT scans showed a bone defect of 1 cm of the lamina papyracea.
      Tumorous tissue passed through this defect reaching the ulcer at the medial
      canthal angle. A biopsy was been taken and revealed granulomatous tissue typical
      for a Wegener's granulomatosis. The patient was sent to an Internal medicine
      department, but he died one month later due to systemic disorders of this
      disease. CONCLUSIONS: Although an acute dacryocystitis is most often the reason
      for a lacrimal sac swelling and inflammation, in all cases of rinsable lacrimal
      pathway and long term lacrimal sac ectasy a neoplastic or a granulomatous reason
      has to be excluded.

PMID- 9541898
TI  - [Inverted transitional cell papilloma of the conjunctiva with peripheral
      carcinomatous transformation].
AB  - BACKGROUND: Inverted papilloma is a benign epithelial neoplasm of mucous
      membrane, usually arising in the nose and paranasal sinuses, much rarer of the
      conjunctiva. Histologically ribbons or bulbous expansions of the epithelium
      invaginate into the underlying connective tissue. In opposite to their sinonasal
      counterparts the few described papillomas of the conjunctiva til now have not
      shown any signs of malignant transformation or recurrence after local excision.
      PATIENT: A 96-year old woman presented with a solid tumour on the nasal bulbar
      conjunctiva of her right eye, which had persisted at least over 6 months. Ocular
      examination showed a 25 x 15 x 15 mm reddish tumour with papillary surface.
      Histologic features of the excised specimen were consistent with inverted
      papilloma, but here were significant carcinomatous foci in peripheral areas. Four
      months later there was a tumour recurrence on the bulbar and tarsal conjunctiva.
      CONCLUSIONS: Inverted papilloma of the conjunctiva is an unusual diagnosis and to
      date there is no previous report of malignant transformation. With only seven
      cases described so far the biologic behavior remains uncertain, but it seems to
      be more aggressive than assumed so far. Complete excision is the treatment of
      choice, but patients should be carefully observed and adjuvant therapy could be
      necessary to ensure tumour control.

PMID- 9541899
TI  - [Screening for bone disease risk with clinical factors in women after physiologic
      menopause].
AB  - BACKGROUND: Densitometric screening for osteoporosis in postmenopausal women has
      not been demonstrated cost-effective. We have tried to identify clinical factors
      for screening previous to densitometry avoiding unnecessary explorations.
      PATIENTS AND METHODS:  SETTING: outpatient clinics of a menopausal unit in a 450
      bed general hospital. Cross-sectional study, in two steps, of two groups of 140
      and 284 women attending for physiological menopause. A clinical questionnaire,
      physical data and lumbar densitometry (Hologic QDR 1000) were obtained
      classifying the cases as "normal" or "low bone mass" (osteopenia or osteoporosis)
      according with the WHO criteria. In the first group a logistic regression
      analysis was done to identify predictive factors for abnormal densitometry, then
      validated in the second group. Sensitivity, specificity, predictive values (PV)
      and classification ability of clinical factors were analyzed. RESULTS: Four
      factors were independent predictors of abnormal densitometry: age > 51 (odds
      ratio [OR] = 6.64; 95% CI, 2.36-18.7); body weight < 70 kg (OR = 4.32; 95% CI,
      1.71-10.09); years of fertility < 32 (OR = 3.77; 95% CI, 1.36-10.04), and number
      of live births > 2 (OR = 3.47; 95% CI, 1.27-9.53). Presence of one factor offers:
      sensitivity 91.9%; specificity 15%; positive PV 66.6%, and negative PV 50%,
      whereas the presence of two factors offers: sensitivity 62.7%; specificity 70%;
      positive PV 79.9%, and negative PV 50.3%. Clinical screening allows, when two
      factors are present, to avoid a 35.5% of densitometries and the false-negative
      cases represent 18%. CONCLUSIONS: Detection of bone-risk clinical factors
      (abnormal densitometry) yields a screening, previous to densitometry, that avoids
      at least one third of explorations in women with physiological menopause,
      improving the efficiency of the test.

PMID- 9541900
TI  - [Impact of medical approach on the presentation form of AIDS defined by clinical
      episodes].
AB  - BACKGROUND: In recent years there has been a change in the opportunistic diseases
      incidence in HIV-infected patients. The change could be related to the use
      antiviral therapy and chemoprophylaxis strategies. The aim of the present study
      was to evaluate if medical intervention is able to modificate the clinical
      presentation of AIDS and the CD4+ lymphocyte counts at time of AIDS diagnosis.
      PATIENTS AND METHODS: The first AIDS-defining condition and the CD4+ count at
      time of AIDS diagnosis were analyzed in 95 HIV-infected patients who developed an
      AIDS-defining disease since April 1989 until March 1996, retrospectively
      reviewed. Patients who had been previously followed at an AIDS Unit were compared
      with those who had not. RESULTS: The frequency of Pneumocystis carinii pneumonia
      as the first AIDS-defining condition was lower in medically followed patients.
      Among this group, AIDS cases who received chemoprophylaxis with isoniazide showed
      a decrease in the rate of tuberculosis. No differences were found in CD4+
      lymphocyte counts between both groups. CONCLUSIONS: As a result of medical
      intervention significant changes have occurred in the spectrum of initial AIDS
      defining conditions in relation to medical intervention; a decrease in the
      frequency of Pneumocystis carinii pneumonia and tuberculosis have been found;
      however, the CD4+ lymphocyte counts at time of AIDS diagnosis are not modificated
      by medical intervention.

PMID- 9541902
TI  - [Osteoporosis screening: from clinical history to physical examination before
      complementary examinations].

PMID- 9541903
TI  - [The intrinsic asthma entity].

PMID- 9541901
TI  - [Prevalence of maternal HIV infection in Catalonia (1994): results of non-related
      anonymous neonatal screening. VIHNADO Group].
AB  - BACKGROUND: Spain has the highest incidence rate of AIDS in Europe. Catalonia
      contributes with around 30% of the AIDS cases detected in Spain. From 1990 to
      1994 the AIDS heterosexual transmission category increased from 9.6% to 14.6% in
      Catalonia. The objective of the study was to determine the HIV prevalence in a
      heterosexual population of pregnant women. SUBJECTS AND METHODS: Unlinked
      anonymous HIV screening by means of an agglutination assay and an enzyme
      immunoassay of eluates of dried blood spots from nearly half of the neonates born
      in Catalonia during 1994. RESULTS: HIV testing was done on 21,074 neonates.
      Overall HIV prevalence was 0.32% (95% CI: 0.25-0.40). It varied from 0.45% in
      Barcelona, 0.38-0.29% in the health regions around Barcelona, to 0.20-0.09% in
      the rest. The mean age of HIV infected women was younger (27) than that of the
      seronegative ones (29) (p < 0.001). The highest prevalence was 0.61% in women
      aged 20-24 years. CONCLUSIONS: The HIV prevalence in the heterosexual population
      of pregnant women in Catalonia is among the highest in Europe. Preventive efforts
      must begin with schoolchildren and be directed to adolescents and young women. It
      is convenient that women who want to become pregnant and mothers receiving
      antenatal care have access to voluntary confidential HIV testing.

PMID- 9541904
TI  - [Orthostatic postural tachycardia: study of 8 patients].
AB  - The occurrence of syncopal episodes is a very frequent event. In the absence of a
      structural systemic or cardiac disease, syncope is resulting of an anomalous
      cardiovascular response neurally mediated by the autonomic nervous system. It is
      the final common manifestation of different abnormal mechanisms and is frequently
      precipitated by orthostatism. Orthostatic intolerance syndrome refers to the
      development of symptoms during the upright posture that disappear in supine
      position. Tachycardia may be one of the clinical features of the syndrome. During
      orthostatic stress a hyperadrenergic response, with maintained increment of heart
      rate and associated symptoms, is developed. Changes in blood pressure may be
      diverse and in some cases hypotension and syncope occurs. Eight patients with
      symptoms of orthostatic intolerance who underwent autonomic evaluation and were
      diagnosed from postural tachycardia are presented. In all the cases an abnormal
      increment of heart rate during tilting was found and it was associated to
      hyperadrenergic symptoms. Evidence of restricted sympathetic impairment was
      observed in six cases with distal reduction of sudomotor function and abnormal
      adrenergic response during Valsalva manoeuvre. Symptoms disappeared or mostly
      subsided with pharmacological (amitriptyline in one case, phenobarbital in
      another one and non-cardioselective beta-blockers in six patients) and non
      pharmacological treatment. In further examinations heart rate and blood pressure
      were normal.

PMID- 9541905
TI  - [Assessment of the reliability of clinical findings: the intraclass correlation
      coefficient].

PMID- 9541906
TI  - [Immunization after hematopoietic stem cell transplantation: review and
      recommendations. Subcommittee of the Spanish Group on Infectious Complications in
      Hematopoietic Transplantation (GETH) and the Spanish Society of Preventive
      Medicine, Public Health and Hygiene].

PMID- 9541907
TI  - [Cerebral ischemia in type I neurofibromatosis].

PMID- 9541909
TI  - [Mean +/- SD, an incorrect expression].

PMID- 9541908
TI  - [Ecstasy: a falsely safe drug].

PMID- 9541910
TI  - [Bone marrow aplasia and ticlopidine].

PMID- 9541911
TI  - [Usefulness of incorporating the analysis of economic assessment in the protocols
      of clinical trials].

PMID- 9541912
TI  - [Multiple myeloma and bone gammagraphy].

PMID- 9541914
TI  - MRI in sporadic Creutzfeldt-Jakob disease: correlation with clinical and
      neuropathological data.
AB  - To ascertain whether increased grey matter signal intensity on T2-weighted images
      in patients with sporadic Creutzfeldt-Jakob disease (CJD) corresponds to the
      stage and severity of this disease, we correlated MRI findings in four of our own
      and previously reported patients with sporadic CJD with the clinical variants,
      neuropathological changes at autopsy, duration of the disease and survival time
      after MRI examination. Of 15 patients with the extrapyramidal type of CJD, 10
      showed increased signal in the basal ganglia on T2-weighted images. One of seven
      patients with the Heidenhain variant had increased signal in the occipital
      cortex. Patients without increased grey matter signal intensity had a longer
      overall duration of CJD (P = 0.035). Although the interval between onset of
      neurological symptoms and MRI was not different, patients without increased grey
      matter signal also survived longer after MRI examination (P = 0.022).

PMID- 9541915
TI  - The corticospinal tract in amyotrophic lateral sclerosis: an MRI study.
AB  - Cortical motor neurone loss and corticospinal tract (CST) degeneration are
      typical of amyotrophic lateral sclerosis (ALS). It is a matter of debate whether
      qualitative assessment of the CST by MRI is useful in the diagnosis. It is also
      an open question whether quantitative determination of the T2 relaxation times
      can improve its value. Signal intensity along the CST on 14 consecutive slices
      was assessed using arbitrary visual rating on double-echo T2-weighted and proton
      density spin-echo images of 21 patients with ALS and 21 age- and sex-matched
      controls. T2 was determined quantitatively. On the T2-weighted images the
      patients' ratings did not differ from that of controls. The T2 of patients and
      controls showed no statistical difference in any slice. There was no correlation
      between T2 and patient age, duration of the disease, or predominant bulbar, lower
      or upper motor neurone signs. The only correlation between MRI findings and
      disease was on the proton-density images: all cases in which the CST was poorly
      seen were controls; a clearly high-signal CST was seen only in the patients. High
      conspicuity of the CST was thus specific but not sensitive for the diagnosis of
      ALS. T2-weighted images and measurement of T2 were not useful for diagnosis.

PMID- 9541913
TI  - [Lupus myelitis: value of magnetic resonance].

PMID- 9541916
TI  - A decrease in cerebral cortex intensity on T2-weighted with ageing images of
      normal subjects.
AB  - To determine the change in intensity in the cerebral cortex on T2-weighted MRI
      with ageing, we reviewed the T2-weighted images of 83 normal subjects and
      measured the signal intensity in the cerebral cortex in 30 subjects randomly
      selected from them. Low-intensity areas were more common in the cerebral cortex
      of the aged. The intensity of different cortical regions varied, and the
      intensity in the temporal and parietal to be decreased with ageing. Presumably,
      this change of the intensity reflects senile changes, although low intensity is
      not evident in the temporal cortex because of its high basal intensity level.

PMID- 9541918
TI  - Sensitivity and specificity of MRA in the diagnosis of neurovascular compression
      in patients with trigeminal neuralgia. A correlation of MRA and surgical
      findings.
AB  - The published rates of operatively confirmed neurovascular compression as the
      cause for trigeminal neuralgia range from 10% to nearly 100%. High-definition
      magnetic resonance angiography (MRA) was performed in 27 consecutive patients (in
      6 cases with 3D reconstructions) to show neurovascular compression
      preoperatively. The MRA findings were compared with the relationship between the
      Vth nerve and the surrounding vessels at surgery. In 23 patients MRA showed
      present neurovascular compression in accordance with surgical findings (18/27 in
      complete accordance of type and side of vessel, site and direction of
      compression). One woman had no neurovascular compression either on MRA or
      intraoperatively. One MRA prediction of neurovascular compression was false, and
      two results were false negative. The sensitivity of MRA was therefore 88.5% but
      the specificity only 50%, if surgical findings are the reference. In one patient
      with right trigeminal neuralgia MRA revealed bilateral neurovascular compression
      of the Vth nerves. Therefore, the overall specificity of MRA might be below 50%.
      In one patient with multiple sclerosis, the decision to operate was markedly
      influenced by the clear finding of neurovascular compression on MRA. The patient
      has been free from trigeminal pain for 149 weeks after microvascular
      decompression. In 6 patients, 3D reconstructions of the MRA data were performed.
      The images helped in 3D visualisation of the operation, but did not yield new
      information about the nature of the vessels revealed, or the site, direction or
      side of the neurovascular compression.

PMID- 9541917
TI  - Unusual MRI findings in grey matter heterotopia.
AB  - We report unusual MRI patterns in patients with grey matter heterotopia. Standard
      T1- and T2-weighted spin-echo and inversion-recovery sequences were used in 22
      patients presenting with seizures or developmental delay. The images were
      reviewed for signal change surrounding white matter and for atypical size,
      morphology or topography. We found 10 cases of subependymal heterotopias 11 of
      focal subcortical heterotopia and of diffuse subcortical heterotopia. On clinical
      or MRI grounds, 8 cases were considered unusual: 2 of the subependymal type, 2 of
      focal subcortical heterotopia with white matter abnormalities, 2 of focal
      subcortical heterotopia with no clinicoradiological correlation 1 of extensive
      hemispheric subcortical heterotopia and 1 of diffuse subcortical heterotopia
      confined to the frontal lobe. The classical classification of heterotopia enables
      easy radiological diagnosis even in cases with unusual patterns. In some cases,
      heterogeneity and high signal in surrounding white matter can be found. Cortical
      dysplasia is the most frequent associated malformation.

PMID- 9541919
TI  - Magnetic resonance angiography of giant intracranial aneurysms.
AB  - 3D time-of-flight magnetic resonance angiography (3D TOF MRA) and 2D MRA with
      presaturation were evaluated in 18 patients with 21 giant intracranial aneurysms.
      3D TOF MRA gave optimal images of proximal unruptured and nonthrombosed
      aneurysms. 2D MRA with presaturation was more informative in cases of distal,
      haemorrhagic or thrombosed aneurysms and in assessment of their components
      (thrombus, haemorrhage, patent residual lumen).

PMID- 9541920
TI  - 11C-tyrosine position emission tomography and 1H magnetic resonance spectroscopy
      of the response of brain gliomas to radiotherapy.
AB  - We monitored 10 patients with unresected (9) or partially resected (1)
      supratentorial gliomas with 11C-tyrosine position emission tomography (TYR-PET)
      before and after radiotherapy. TYR-PET tumour volumes were measured using a
      threshold technique. In seven patients the tumour volume decreased after
      radiotherapy, although all gliomas persisted on TYR-PET images. In eight patients
      the tumour protein synthesis rate (PSR) was calculated using a dynamic study
      protocol in combination with a PATLAK analysis. There were no changes in PSR
      after radiotherapy, but the PSR was calculated on the remaining tumour volume
      using the same threshold technique as before therapy, i.e. the decrease in tumour
      volume was not taken into account. In eight patients the PET data were compared
      with magnetic resonance spectroscopic imaging (1H-MRSI) performed simultaneously.
      Although there was no statistically significant correlation between TYR-PET
      volume changes and 1H-MRSI choline level we observed a simultaneous decrease in
      volume and choline in four patients.

PMID- 9541921
TI  - Imaging of the neurological complications of infective endocarditis.
AB  - We describe the findings on CT or MRI in five patients with neurological symptoms
      and underlying infective endocarditis (IE). We noted the size, number, and
      distribution of lesions, the presence or absence of haemorrhage, and contrast
      enhancement patterns. The number of lesions ranged from 4 to more than 10 in each
      patient. Their size varied from punctate to 6 cm; they were distributed
      throughout the brain. The lesions could be categorized into four patterns based
      on imaging features. A cortical infarct pattern was seen in all patients. Patchy
      lesions, which did not enhance, were found in the white matter or basal ganglia
      in three. Isolated, tiny, nodular or ring-enhancing white matter lesions were
      seen in three patients, and parenchymal haemorrhages in four. In addition to the
      occurrence of multiple lesions with various patterns in the same patient,
      isolated, tiny, enhancing lesions in the white matter seemed to be valuable
      features which could help to differentiate the neurological complications of IE
      from other thromboembolic infarcts.

PMID- 9541922
TI  - Lymphocytic adenohypophysitis: skull radiographs and MRI.
AB  - We report the skull radiograph, CT and MRI findings in three patients with
      lymphocytic adenohypophysitis mimicking pituitary adenoma. All cases were
      associated with pregnancy. CT demonstrated a pituitary mass but did not
      differentiate lymphocytic adenohypophysitis from pituitary adenoma. The skull
      radiographs showed either a normal sella turcica or minimal abnormalities; they
      did not show ballooning or destruction. The MRI appearances were distinctive:
      relatively low signal on T1-weighted images; preservation of the bright posterior
      pituitary lobe despite the presence of a relatively large pituitary mass, less
      common in macroadenomas; marked contrast enhancement compared with pituitary
      macroadenomas; and dural enhancement adjacent to a pituitary mass.

PMID- 9541923
TI  - Prognostic value of proton MR spectroscopy of cerebral hemisphere tumors in
      children.
AB  - We studied 14 young people with newly diagnosed hemisphere tumors, aged from 3 to
      20 years (average 10 years). All underwent surgery following MR imaging (MRI) and
      spectroscopy (MRS). The tumors studied were three glioblastomas, one each of
      ganglio-glioblastoma, primitive neuroectodermal tumor (PNET), rhabdoid teratoid
      tumor, pilocytic astrocytoma, ependymoma, anaplastic ependymoma, and gliomatosis
      cerebri, and four gangliogliomas. Four patients died; ten patients are alive
      (five with stable residual tumor, five with no evident tumor). Images and spectra
      were acquired on a 1.5-T imager. Proton MRS was performed before gadolinium
      injection in all but one case. Single-voxel techniques were utilized in all
      cases, using a spin-echo or STEAM sequence with a long echo time (135 or 270 ms).
      Peak areas of N-acetyl aspartate (NAA), choline (Cho), and creatine and
      phosphocreatine (Cr) were assessed. The NAA/Cho peak-area ratio was very low in
      the patients who died (mean +/- s.d. 0.20 +/- 0.14), and higher in the patients
      who are alive (0.74 +/- 0.47; P = 0.007 by two-tailed t-test). The Cr/Cho peak
      area ratio also followed a similar trend for the two groups (mean +/- s.d. 0.17
      +/- 0.07 and 0.49 +/- 0.30, respectively; P = 0.01 by two-tailed t-test).

PMID- 9541924
TI  - Meningoradiculitis due to borreliosis presenting as low back pain only.
AB  - We report a child with Borrelia burgdorferi meningoradiculitis. This entity, also
      known as Bannwarth syndrome, is rare and its presentation with low back pain only
      is even more unusual. The MRI findings can suggest the diagnosis.

PMID- 9541926
TI  - [Insertion mutation 22w of Drosophila melanogaster blocks the cell cycle in
      metaphase].
AB  - We studied the cytogenetic effect of P[lArB] transposon insertion into the 42A
      region of the second D. melanogaster chromosome (mutation 22w). This mutation was
      shown to induce metaphase (rarer anaphase) block of the cell cycle. The
      chromosomes have an abnormal "lump" morphology. Possible involvement of the
      corresponding gene product in functioning of the cell oscillator is discussed.

PMID- 9541925
TI  - [Current status of the gap junction problems and and views on their role in
      development].
AB  - This review presents published data on various aspects of gap junction
      functioning during development. The process of formation of these junctions and
      their structure, along with relationships between molecular characteristics of
      connexins and properties of gap junctions channels are considered in detail. Some
      newly discovered functions of gap junctions in early embryonic development, their
      participation in the formation of various cellular compartments and in
      coordinated behavior are discussed; their relationship with other types of cell
      interactions is also reviewed. Promising problems for further research are
      outlined.

PMID- 9541927
TI  - [Three-dimensional histoarchitectonics of the larval epidermis of the grass
      frog].
AB  - We have conducted theoretical and experimental study of the three-dimensional
      structure of epidermis in the larva of the grass frog. Three-dimensional modeling
      of cell shape and mutual arrangement yielded several variants of cell-to-cell
      connections at the apical, basal, and intermediary levels of the cell sheet.
      Concepts of the normal and inverted orientation of the epithelial sheet have been
      introduced, and arguments for the existence of translation symmetry in this sheet
      were presented. At least two topological variants of three-dimensional
      organization can be found in the larval epidermis of the grass frog. Comparison
      of theoretical concepts and experimental results allowed us to conclude that the
      models developed by us are in good agreement with actual existing patterns of the
      epithelial structure; these models contribute to better reconstruction of their
      three-dimensional structure.

PMID- 9541928
TI  - [Variation and asymmetry of axial rudiments of Xenopus laevis embryos in response
      to a disturbance of cell movements and tension fields in the marginal gastrula].
AB  - We studied changes of volume, disturbances of mutual volumetric proportions, and
      asymmetry of axial rudiments in the embryo of Xenopus laevis after partial
      separation of the dorsal blastopore lip with P-shaped incisions from the
      remaining part of the marginal zone. This was conducted at the stage of early
      gastrula. The incision was directed either towards the lip (series 1) or away
      from the lip (series 2). Gastrulation movements were inhibited in both series of
      experiments. In series 1, the dorsal zone acquired isotropic structure, and in
      series 2, it quickly restored the initial longitudinal tensions. Sometimes and
      pairwise (but strongly asymmetric) notochord rudiments were formed in the lateral
      lips of the unclosed blastopore. In both experimental series, we have noted a
      high (exceeding the control by an order of magnitude) variation in the volume and
      mutual proportions of axial rudiments, their high asymmetry, and low volume
      correlations. Asymmetry of chordal rudiments in the lateral lips was higher in
      series 1, and the occurrence of the notochord in the dorsal region was higher in
      series 2. The results are discussed from the point of view of a possible role of
      gastrulation movements and the associated tension fields in the marking of axial
      rudiments.

PMID- 9541929
TI  - [Relationship between regulatory effects of serotonin and testosterone on the
      development of the LHRH producing system of the rat brain during the prenatal
      period of development].
AB  - We have performed radioimmunoassay of LHRH in rostral and septal-preoptic brain
      regions, as well as in mediobasal hypothalamus of male and female fetuses at day
      21 of the prenatal period after the injection to pregnant females on days 11-20
      of gestation of either p-chlorophenylalanine (PCPA) or of a combination of PCPA
      with ethane-1,2-dimethane sulfonate (EDS). Control animals received the injection
      of the same volume of physiological saline. In the control fetuses, both males
      and females, the level of LHRH in the rostral brain region was significantly
      lower than in the septal-preoptic region. The administration of PCPA increased
      the level of LHRH in the rostral brain region and decrease it in the septal
      preoptic region, the effect being more prominent in males. When EDS was
      administered on the background of PCPA administration, sex-related differences in
      the level of LHRH in the studied brain regions were no longer present. It is
      proposed that serotonin stimulates migration of LHRH neurons in rostral-caudal
      direction, and this effect of serotonin is more significant in males, since it is
      potentiated by testosterone.

PMID- 9541930
TI  - [Dynamics of changes in various adaptation components in Drosophila ontogenesis].
AB  - We studied the effect of parental age on expressivity of trait eyeless,
      fertility, heat resistance, and life span of Drosophila offspring. We found that
      these characteristics show different changes in the offspring of aging parents.
      The ontogenetic curve of changes of expressivity of the trait eyeless and
      fertility is similar to the curve of normal distribution. As concerns the changes
      in heat resistance, they are complex in nature: the offspring of "young" or "old"
      parents has the highest heat resistance. Age of parents in the studied range does
      not significantly affect the mean life span of the offspring.

PMID- 9541931
TI  - [Differential activity of chromosomal nucleolus-organizer regions during
      postimplantation embryogenesis in mink].
AB  - Using cytological preparations, we have conducted analysis of the activity of
      chromosomal nucleolus organizers during postimplantation embryogenesis in mink.
      The analysis was conducted by visual evaluation of their staining pattern with
      silver nitrate and incidence rate in satellite associations. The data obtained
      provide evidence that each nucleolus organizer during embryonic mink development
      shows a characteristic pattern of activity depending on cell type, tissue type,
      and the stage of development and also depending on changing location in the
      interphase nucleus. We discuss biological significance of the existence of
      "indispensable long-satellite" chromosome in the genome.

PMID- 9541932
TI  - [Evaluation of the epidemiologic importance of populations of malaria mosquitoes
      (Culicidae: Anopheles) in the northern zone of the Tien Shan region].
AB  - Six species of the genus Anopheles are recorded in the North of the Tien Shan. As
      far as an epidemiological situation in the region in question in gets worse, the
      factors determining links between people and mosquitoes, namely the food
      preference of different species of Anopheles, the frequency of actual mosquito
      attacks and the physiological age of mosquito females have been analysed. It is
      shown, that A. claviger and A. messae are the most probable potential malaria
      vectors in mountain regions, and A. hyrcanus--in lower parts of the Tien Shan.

PMID- 9541933
TI  - [Ecology of flea groups of the species conformis (Siphonaptera: Pulicidae:
      Xenopsylla) of the fauna of Russia and adjacent countries (review)].
AB  - Within the boundaries of the former USSR, the northern part of the conformis
      group distribution is located. It spreads over the arid regions of the Trans
      Cacucasus, Pricaspijckaja lowland, Kazakhstan and Middle Asia. In this area 10
      species and subspecies occur. They are mainly parasites of gerbillins. Unlike
      many other Siphonaptera the conformis fleas, when in the host's home, do not
      concentrate in the nest but inhabit the passages of burrow and food chambers
      throughout the year. On this reason the preimaginal development and existence of
      the adults take place not at the temperature of the habitable nest, which is
      heated by the host body, but at the temperature of the soil at a depth of burrow.
      The temperature threshold for preimaginal development of conformis fleas is
      reported to be 10-12 degrees. Temperature below the threshold is fatal for all
      immature instars. On the contrary the imago can survive at freezing temperature.
      The annual cycle of the conformis fleas is characterized by the presence of
      adults throughout the year. They breed in the warmer season and overwinter in the
      state of reproductive diapause. In this state the fleas are able to attack the
      host and to feed but do not deposit eggs. In the north deserts the reproduction
      begins at the early April and terminates at the early September. Southern, the
      reproductive period is longer. Furthermore, the complete interruption of the
      reproduction in the autumn-winter time may be absent as it was observed in X.
      gerbilli gerbilli and X. hirtipes in the south of the Middle Asia. On the other
      hand it is noted that in southern deserts the rate of oviposition falls in the
      most hot time. The number of generation per year in the conformis fleas varies
      from 2-3 in north deserts to 6-7 in south ones. The flea populations peak in late
      autumn when the insects cease to bread. The high abundance is maintained until
      springtime. After the diapause is ceased and the fleas begin breeding their
      abundance declines. In the late spring and early summer the emergence of adults
      begins and the populations increase. In a mild of summer the second fall takes
      place and then the fall is replaced by the autumnal peak. On their main hosts the
      conformis fleas prevail over all other species of Siphonaptera especially for
      warmer time when their quota among other fleas does not descend as a rule below
      90% but more oftently it approaches to 100%. The fleas of this group and
      especially species parasitizing Rhombomys opimus are remarkable for the high
      level of their abundance. In the northern deserts in the periods of the most high
      abundance (late autumn, winter and early spring) the number of fleas per burrow
      occupied by family of Rh. opimus exceeds usually 1000 specimens and sometimes it
      can reach several thousands. In the southern deserts the abundance of the fleas
      is lower but the period of their active parasitizing is longer. In the species
      parasitizing Rh. opimus it is shown that in a complex burrow only some part of
      fleas has the possibility to feed regularly. In the spring and summer the
      percentage of fleas daily attacking the host varied from 17 to 86% and from 10 to
      150 ectoparasites feed daily on one animal depending on the quantity of fleas and
      of hosts in the burrow. The number of attacking fleas is regulated by behaviour
      of the hosts, which change the used parts of burrow when the fleas are crowded
      there.

PMID- 9541934
TI  - [Ultrastructural features of histopathologic changes at the site of attachment of
      the larva of the Ixodid tick Haemaphysalis longicornis to the body of the host].
AB  - This article continues the series of electronic microscopical investigations of
      tick attachment and host's inflammatory reaction in the attachment site. In all
      this works we used larvae of different Ixodid ticks but the same species of the
      host (white mouse), Ixodid species having different type of attachment.
      Dermacentor marginatus (Amosova, 1989a) is characterized by the superficial
      penetration of mouth parts, the abundance of cement around them and on the
      surface of the host's skin, the mouth parts of Hyalomma asiaticum are fully
      inserted and the superficial cement is minimal (Amosova, 1989b) and Ixodes
      ricinus has mouth parts inserted more deeply in the skin tissue of the host and
      the cement substance localised only on the surface of the skin at the 1st and 2nd
      days of feeding period. For this investigation we choose Haemaphysalis
      longicornis because it is known (see Kemp et al., 1982) that genus Haemaphysalis
      has the most superficial localisation of the mouth parts in the attachment site.
      We have studied a fine structure of cement cone and the cement substance
      surrounding the mouth parts in the skin and have demonstrated that it is very
      similar to the Dermacentor marginatus cement structure. The pattern of cellular
      response is similar to D. marginatus lesion too.

PMID- 9541935
TI  - [Detection of the spirochete Borrelia burgdorferi in Ixodid ticks using solid
      phase immunoenzyme analysis (ELISA)].
AB  - 138 Ixodes persulcatus and 140 I. ricinus ticks were collected by flagging in the
      Moscow region of Russia in April-September 1995. Borrelia burgdorferi infection
      rates of 171 (73 I. persulcatus and 98 I. ricinus) flat ticks were ascertained by
      both a dark-field microscopy and an enzyme-linked immunosorbent assay (ELISA).
      The ELISA is based on the use of "capture" monoclonal antibodies (mABs) to Osp A
      L12-9B4 (2D8) in combination with rabbit antisera to Osp A and B. This mAB reacts
      with B. burgdorferi sensu stricto well as B. garinii, it has no reactivity with
      B. afzelii (isolate Iper3, Russia). Darkfield examination showed 11% infected
      ticks. The Osp A antigen positivity rate was 12%. 87% concordance between the two
      assays was recorded. In this study we investigated homogenates of 94 (33-I.
      persulcatus, 60-I. ricinus and 1 hymph Ixodes sp.) engorged ixodid ticks removed
      from humans for the presence of B. burgdorferi by the ELISA. Osp A of B.
      burgdorferi was found in 18 (19%) of the ticks. Osp A was also found in 57 of 107
      (53%) ixodid ticks collected on vegetation in the Moscow region. This group of
      ticks was not tested by a dark-field microscopy as they died shortly after being
      collected.

PMID- 9541936
TI  - [New data on fauna and systematics chiggers of the autumnalis group
      (Trombiculidae: Neotrombicula)].
AB  - The study of the species group autumnalis in genus Neotrombicula is carried out.
      Composition of the group and diagnoses of species are changed, data on
      variability are reported. A new species, N. oculata sp. n., is described. The new
      species is similar to N. turkestanica Kudryashova, 1993 and differs from it by
      disproportionaly large eyes, a little more numerous setae of idiosoma (NDV = 66
      78 against 58-69) and their lesser lengths (Dm = 41-46 against 45-49), a lesser
      width of scutum (AW = 71 against 76). One species, N. alexandrae Stekolnikov,
      1993, is synonymized with N. delijani Kudryashova, 1977. For N. delijani and N.
      turkestanica new localities and new hosts are reported.

PMID- 9541937
TI  - [Benign microglandular prostate lesions. Diagnostic criteria na differential
      diagnosis].
AB  - The scope of the present review is to define diagnostic criteria of benign
      prostatic lesions causing diagnostic difficulty in surgical pathology. The
      prostate harbors a variety of small acinar lesions that may mimic prostate cancer
      in biopsy specimens. Generally, the most important diagnostic clues are obtained
      on low-power magnification by assessing architectural features. Atypical
      adenomatous hyperplasia (AAH) is a small acinar proliferation closely related to
      hyperplastic glands. Diagnostic features of postatrophic hyperplasia include a
      lobular small acinar proliferation associated with atrophic and dilated acini.
      Basal cell hyperplasia and sclerosing adenosis show characteristic stromal
      changes that are uncommon in prostate cancer. Additional cytological features and
      intraluminal secretions are also important in the diagnostic evaluation of small
      acinar lesions in biopsy specimens. Negative immunohistochemical results obtained
      with basal-cell-specific cytokeratins should be evaluated in context with other
      diagnostic criteria. The unequivocal demonstration of basal cells in small acinar
      lesions excludes invasive cancer. Other rare small acinar lesions must be
      recognized when assessing biopsy specimens, including verumontanum-mucosa
      hyperplasia, Cowper's glands and mesonephroid hyperplasia. The various small
      acinar lesions discussed in the present review have no clinical significance,
      except atypical adenomatous hyperplasia (AAH), which may be a precursor of small
      acinar cancer of the transition zone. The biological and clinical significance of
      AAH, however, remains to be established.

PMID- 9541938
TI  - [Morphogenesis of benign prostatic hyperplasia and prostatic carcinoma].
AB  - Enlargement of the prostate is an age-related, physiological process that is
      unique in human tissue. The prostate gland is the most common site of neoplastic
      disorders in men. Despite the growing impact of the various prostate diseases in
      terms of morbidity and mortality, the pathogenesis of benign prostate hyperplasia
      (BPH) and prostate cancer remains poorly understood. This reflects the complex
      composition of the gland with different anatomic, cellular and functional
      compartments that are differentially involved in benign and malignant disease
      processes. The present review summarizes new concepts on the morphogenesis of
      normal and abnormal growth in the human prostate. There is increasing evidence
      that prostatic stem cells are located in the basal cell layer that is basically
      involved in normal growth and the development of glandular hyperplasia and
      prostate cancer. High-grade prostatic intraepithelial neoplasia is considered the
      most likely precursor of clinically important cancer of the peripheral zone.
      Severe differentiation and proliferation abnormalities occur during malignant
      transformation of the prostatic epithelium. These premalignant changes are
      associated with abnormal expression of growth factor receptors, oncogene and
      suppressor gene products and genetic instability. During the process of stromal
      invasion the transformed cells lose their basal cell phenotype and produce
      basement membrane-like matrices. Common prostate cancer is mainly composed of
      exocrine cell types that remain androgen-responsive even in hormone-independent
      disease. The frequent occurrence of neuroendocrine differentiation in common
      prostate cancer reflects the differentiation potency of its stem cells. The
      endocrine phenotype derives from exocrine tumor cells via intermediate
      (amphicrine) cell types. Neuroendocrine tumor cells consistently lack the nuclear
      androgen receptor and represent an androgen-insensitive cell population in
      prostate cancer.

PMID- 9541939
TI  - [Diagnostic criteria of prostatic carcinoma].
AB  - The histological diagnosis of prostate cancer relies on a combination of
      structural and cytological findings. Structural features are assessed at low
      power magnification. Malignant glands are recognised by their abnormal size,
      shape and location in relation to the surrounding benign glandular structures.
      The presence of pathological intraluminal secretions (pink amorphous secretions,
      crystalloids, blue-tinged mucinous secretions) is always suspicious, but not
      diagnostic for prostate cancer. Cytological criteria including nuclear and
      nucleolar enlargement, hyperchromasia and cytoplasmic changes have to be
      evaluated in comparison with the cytological features of surrounding benign
      glands. The presence of prominent nucleoli is neither diagnostic for malignancy
      nor represents an absolute requirement for the diagnosis of prostate cancer. The
      basal cell layer is absent in invasive adenocarcinoma, an important feature that
      has to be evaluated with care since benign glands may also lack detectable basal
      cells. The immunohistochemical demonstration of basal cells with high molecular
      weight cytokeratins excludes invasive cancer. This article reviews the
      histological criteria for the diagnosis of prostate cancer, including variants of
      common adenocarcinoma and therapy-induced changes.

PMID- 9541940
TI  - [Diagnostic criteria and differential diagnosis of prostatic intraepithelial
      neoplasia].
AB  - Prostatic intraepithelial neoplasia (HGPIN) is considered the most likely
      precursor of clinically significant prostate cancer. Biopsy remains the only
      definitive method for detecting these premalignant lesions. In this article we
      review the diagnostic criteria of HGPIN and discuss histological features that
      allow their distinction from other benign and malignant lesions. PIN is
      recognised at low power magnification as a thickened, basophilic and
      hyperchromatic epithelium in pre-existing acinar duct structures. This important
      histological feature is due to nuclear crowding and stratification. Distinction
      between HGPIN and low grade PIN (LGPIN), a lesion with little clinical
      significance, is made mainly on the presence or absence of prominent nucleoli.
      HGPIN lesions always retain an intact or fragmented basal cell layer. The
      different growth patterns of HGPIN (tufting, micropapillary, cribriform and flat)
      have no clinical significance but should be considered in the differential
      diagnosis together with normal structures, and both benign and malignant lesions.
      HGPIN has a high predictive value as a marker for prostate cancer but should not
      influence therapeutic decisions. Its identification in biopsy specimens warrants
      close surveillance with repeated biopsy.

PMID- 9541941
TI  - [Prognostic factors of prostatic carcinoma].
AB  - The histological classification or typing of prostate carcinoma combined with
      histological grading according to Gleason or WHO with nucleolar subgrading are
      the most important prognostic factors in carcinoma of the prostate. Prostatic
      cancer is the most common malignancy in adult males and is the second-most-common
      cause of cancer death in the USA. The histological Gleason grade may be reduced
      if only a small amount of tumor tissue is present in the core needle biopsy, in
      contrast to the combined histological and cytological grading according to WHO
      with nucleolar subgrading. When there is sufficient carcinomatous tissue in the
      core needle biopsy, there is no difference from that in radical prostatectomy
      tissue, because most cases of prostatic carcinoma are highly malignant. DNA
      cytometry, immunohistochemical analysis with Ki67/Mib1 or molecular pathological
      studies with the tumor suppressor gene p53 or apoptosis suppressing oncoprotein
      bcl2 and the density of blood capillaries may be helpful as additional prognostic
      factors, but only together with the results of the primary histological section.
      For comparison of grading results with the international literature both grading
      systems should be used according to Gleason and WHO with nucleolar subgrading.

PMID- 9541942
TI  - [Cytopathology of the prostate].
AB  - Transrectal fine-needle aspiration biopsy (FNAB) of the prostate under digital
      control is a cheap and rapid method for diagnostic evaluation of palpable and non
      palpable nodules, yielding high sensitivity (ca. 95%) and a low complication rate
      (< 1%). Its specificity amounts to > 97%. The scarcity of urologists trained in
      the FNAB method and of pathologists experienced in cytology of the prostate limit
      the clinical application so far. Besides various forms of prostatitis, five
      different types of cancer can cytologically be differentiated. While PIN I cannot
      be cytologically identified, PIN II/III lesions may lead to false-positive
      diagnoses. Cytologic grading of adenocarcinomas of the prostate is of
      statistically proven prognostic validity and strictly correlated with its
      histologic counterpart. Preoperative, radiologically controlled FNAB of pelvic
      and paraortal lymph nodes has sensitivity of ca.86% and specificity of 100%. It
      thus helps to avoid unnecessary prostatectomies if nodal tumor spread has
      preoperatively been proven. Diagnostic DNA cytometry is able to identify those
      prostatic cancer patients who do not reveal significantly increased risk of tumor
      progression or decreased survival probability, even without therapy (constantly
      and representatively diploid and tetraploid patterns). Patients with DNA
      tetraplid histograms may show deteriation of prognosis under hormonal therapy.
      DNA-aneuploid prostatic cancers should not be subjected to a "wait and see"
      strategy; they do not respond to hormonal therapy.

PMID- 9541943
TI  - [What does the urologist expect and hope for from the pathologist in diagnosis of
      prostate carcinoma].
AB  - Prostate cancer has become the most common cancer in males in Western countries.
      In the United States 317,000 men were newly diagnosed with this disease in 1996.
      Screening efforts will identify increasing numbers of men who will be scheduled
      for prostate biopsy. Since the progression of prostate cancer varies widely from
      rapid tumor growth with early distant metastases to slow growth with good
      prognosis, it is of utmost importance that prognostic parameters be identified
      which allow the course of the disease to be predicted. Thus, the correct
      pathohistological staging, the evaluation of different grading systems, and the
      biological impact of positive surgical margins after radical prostatectomy
      requires collaboration between urologists and pathologists.

PMID- 9541944
TI  - [Cytogenetic changes in prostatic carcinoma].
AB  - Development and progression of tumors is driven by a malfunction of specific
      genes. Although prostate cancer is one of the most frequent tumors, little is
      known about the genes involved. Cytogenetic and molecular examinations have shown
      that chromosomal deletions most frequently involve 7q, 8p, 10q, 13q, 16q, 17p and
      the Y chromosome. These loci may carry tumor suppressor genes with relevance for
      prostate cancer. DNA sequence copy number gains were most frequently observed at
      chromosomes 7, 8q, and 11q. These regions may carry currently unknown oncogenes.
      There is increasing evidence for a clinical relevance of genetic alterations.
      Polysomies of several chromosomes were shown to be associated with poor prognosis
      of prostate cancer patients. Androgen receptor amplification can be found in
      hormone-refractory carcinomas which may respond to total androgen blockage. For
      the future it is hoped that the identification of the genes involved in prostate
      cancer and the determination of their function could allow for significant
      improvements of treatment strategies for prostate cancer patients.

PMID- 9541945
TI  - [Spindle cell tumors and tumor-like changes of the prostate and surrounding
      tissue].
AB  - Spindle cell lesions of the prostate and surrounding tissues include mesenchymal
      and epithelial tumors and tumorlike lesions, such as postoperative spindle cell
      nodules (PSN) and pseudosarcomatous fibromyxoid tumors (PFMT). PSN and PFMT are
      possibly related fibroblastic and myofibroblastic proliferations respectively.
      However, they may be misinterpreted as sarcomas. PSN typically are detected
      incidentally several weeks or months after urological procedures such as
      cystoscopy. PFMT only rarely reveals a urological history, however, reaching back
      for several years; here, more often there is a clinical presentation with dysuria
      and/or hematuria. Important for the differential diagnosis of PSN and PFMT or
      sarcomas is not only a histological examination, including immunohistochemistry,
      but also a close clinicopathological correlation. Nevertheless, in some cases it
      may be impossible to reach a final diagnosis.

PMID- 9541946
TI  - [Urothelial tumors and preneoplasias. Diagnostic problems and their clinical
      consequences].
AB  - The surgical pathology of biopsies or electroresection specimens taken from
      clinically suspicious or overt tumors in the urinary bladder encompasses the
      evaluation of a few parameters. This should allow the segregation of bladder
      tumor patients into subgroups with distinct clinical features and biological
      behavior, thus providing a rationale for choosing the best available therapy. In
      essence, the pathologist's role entails a careful morphologic assessment of the
      primary tumor, including evaluation of the histologic type, the growth pattern,
      the tumor grade, the tumor stage, and finally the presence and type of primary or
      tumor-associated flat intraurothelial lesions. Whereas the growth pattern of a
      lesion can be readily recognized, the correct grading and staging of papillary
      tumors are often more dependent on the complexity of the individual case and the
      experience of the pathologist due to the inherent subjectivity of the field and a
      lack of standardized criteria. These problems of intra- and interobserver
      variability are intimately coupled with the characteristics of the material, that
      is, bad orientation and tangential sectioning, thermal injury, crush and fixation
      artifacts, and limitations of the size of the samples. The correct evaluation and
      interpretation of flat intrauorothelial lesions suffer from similar difficulties
      and are further complicated by a confusing categorization and terminology.
      Although new modalities and molecular approaches have been introduced in recent
      years in an effort to overcome some of these obstacles, morphology still remains
      the most effective means to assess the biological behavior and prognosis of
      urothelial bladder cancer. The present article therefore addresses some of the
      diagnostically and clinically most relevant controversies and aims to give some
      useful hints for the evaluation of the above-mentioned morphological parameters.
      In addition, it adds some remarks on the morphological basis and diagnostic
      validity of urinary cytology in primary diagnosis and, more importantly,
      monitoring of bladder cancer patients.

PMID- 9541948
TI  - Two-stage sampling in surveys to substantiate freedom from disease.
AB  - Disease in livestock populations tends to cluster at the herd level. In order to
      account for this--and to overcome the problems of simple random sampling from a
      very large population--large-scale livestock surveys usually involve two-stage
      sampling. However, the use of two-stage sampling presents particular problems for
      sample-size calculation and analysis. We developed a probability formula for two
      stage sampling, initially based on the assumption of a perfect test. We used this
      formula to demonstrate how combinations of first-stage (number of herds) and
      second-stage (number of animals in selected herds) sample sizes can be altered to
      achieve a least-cost survey, and used simulation to validate the formula. To
      overcome the unrealistic assumption of a perfect test, we then applied an exact
      probability formula (which takes imperfect tests and finite population sizes into
      account) to the two-stage sampling design. An example is given which shows how
      implementing the formula with the FreeCalc computer program allows least-cost
      first and second-stage sample sizes to be calculated.

PMID- 9541947
TI  - A new probability formula for surveys to substantiate freedom from disease.
AB  - Surveys to substantiate freedom from disease are becoming increasingly important.
      This is due to the changes in rules governing international trade in animals and
      animal products, and to an increase in disease eradication and herd-level
      accreditation schemes. To provide the necessary assurances, these surveys must
      have a sound theoretical basis. Until now, most surveys have been based on the
      assumption that the screening test used was perfect (sensitivity and specificity
      both equal to one), and/or that the study population was infinite. Clearly, these
      assumptions are virtually always invalid. This paper presents a new formula that
      calculates the exact probability of detecting diseased animals, and considers
      both imperfect tests and finite population size. This formula is computationally
      inconvenient, and an approximation that is simpler to calculate is also
      presented. The use of these formulae for sample-size calculation and analysis of
      survey results is discussed. A computer program, 'FreeCalc', implementing the
      formulae is presented along with examples of sample size calculation for two
      different scenarios. These formulae and computer program enable the accurate
      calculation of survey sample-size requirements, and the precise analysis of
      survey results. As a result, survey costs can be minimised, and survey results
      will reliably provide the required level of proof.

PMID- 9541949
TI  - Associations between passive immunity and morbidity and mortality in dairy
      heifers in Florida, USA.
AB  - A prospective cohort study was undertaken to determine calf-level factors that
      affected calf health status between birth and 6 months of age. A convenience
      sample of approximately 3300 female Holstein calves born in 1991 on two large
      Florida dairy farms was used for the study. Data collected on each calf at birth
      included farm of origin, weight, height at the pelvis, birth date, and serum
      total protein (a measure of colostral immunoglobulin absorption). Birth season
      was dichotomized into summer and winter using meteorological data collected by
      University of Florida Agricultural Research Stations. Health data including date
      of initial treatment and number of treatments were collected for the diseases
      diarrhea, omphalitis, septicemia and pneumonia. All calves were followed for 6
      months. Cumulative incidences of mortality and occurrence of diarrhea,
      omphalitis, septicemia and pneumonia were 0.12, 0.35, 0.11, 0.24 and 0.21,
      respectively. Serum total protein (TP) was a significant risk factor for
      mortality. The association of TP and mortality was quadratic and showed a
      dramatic decrease in mortality as TP increased from 4.0 to 5.0 g/dl, a small
      improvement from 5.0 to 6.0 g/dl and virtually no improvement in mortality rates
      as TP increased over 6.0 g/dl. The hazard mortality ratio was constant from birth
      to six months, indicating that the increased risk of mortality associated with
      low levels of TP was evident through six months of age. No interactions between
      TP, farm, season, or birth weight were found in these analyses. Serum total
      protein concentration was a significant risk factor for the occurrences, age of
      onset and severity of septicemia and pneumonia. The association between TP and
      septicemia was linear and an interaction with birth season was found. The
      association between TP and pneumonia was quadratic, and in contrast to the TP-and
      septicemia relationship, the morbidity hazard ratio for pneumonia was not
      constant over the time measured; that is, colostral immunity protected the calf
      from developing pneumonia early in life, but this effect disappeared as the calf
      got older. Total protein was not a significant risk factor for diarrhea or
      omphalitis.

PMID- 9541950
TI  - The effect of a badger removal programme on the incidence of tuberculosis in an
      Irish cattle population.
AB  - The risk of a confirmed tuberculous herd restriction was examined using a
      logistic model for herds involved in the East Offaly Badger Research Project,
      Ireland, from 1988-1995. Cattle herds present in the badger-removal area had a
      significantly lower proportion of new confirmed tuberculous herd restrictions
      compared with cattle from an area where no systematic badger removal was
      attempted.

PMID- 9541951
TI  - Associations between individual cow factors and milk-protein production.
AB  - Associations between stage of lactation, cow characteristics, and protein
      production were evaluated using data from a 2-year period on 75 Ontario, 5
      Alberta, and 3 Nova Scotia dairy farms. Individual-cow protein production was
      defined by 305-day protein yield and by the estimated breeding value for protein
      yield. Lactation curves for average daily protein yield were computed by parity,
      breed, and season of calving. Mean protein yield was highest in early lactation.
      However, there was no pronounced peak in daily protein yield. Parity was
      positively associated with 305-day protein yield and negatively associated with
      the estimated breeding values for protein yield. First-calf heifers had lower
      protein yields in early lactation and a slower rate of decline in protein yield
      in late lactation, as compared to later parity cows. Holstein cows had higher
      unadjusted protein yields and lower protein yields after adjusting for milk yield
      than other breeds. Holstein cows had significantly higher protein yields early in
      lactation compared to other breeds, but the rate of decline in protein production
      in late lactation was also greater. Season was associated with 305-day protein
      yield; the highest protein yields occurred in cows calving in the fall and winter
      months, but these cows had the greatest rate of decline in protein production in
      late lactation.

PMID- 9541952
TI  - [Recovery of memory impaired during learning in chickens: reversal of amnesia
      induced by blockers of protein synthesis].
AB  - Administration of protein synthesis inhibitors (PSI) produced an obvious amnesia
      in chicks (20-25% of avoidance responses). A "reminder" treatment: giving of
      environmental clues presented during learning, recovered of the learned avoidance
      response up to level of the control animals (75-80%). The data obtained suggest a
      possibility of memory recovery following the "reminder" treatment.

PMID- 9541953
TI  - [Systemic analysis of neuroimmune mechanisms of memory].
AB  - Administration of IL-1 beta and 125-129 fragment of alpha 2-interferon improved
      learning and retention of active avoidance behaviour in memory in rats. It also
      improved the correlation between intersignal runs and success of the avoidance
      behaviour learning. The data obtained suggest that an activation of the
      intersignal retention process is one of the mechanisms of the immunomodulators
      effect on learning and memory.

PMID- 9541954
TI  - [Recovery of normal stressor reactions in rats with disrupted brain limbic
      structures by delta-sleep inducing peptide].
AB  - Administration of the DSIP improved resistance against stress in rats with septal
      or amygdalar brain lesions, the latter structures playing an important part in
      the resistance mechanisms. Bilateral lesion of these structures significantly
      decreased the resistance against emotional stress in rats.

PMID- 9541955
TI  - [Correlates of sequential elements of bimanual behavior in the neuronal activity
      of the monkey neostriatum].

PMID- 9541956
TI  - [Response of the hypothalamic neurons to stimulation of the vestibular nerve and
      lateral vestibular nucleus in rabbits].
AB  - Effects of single, double, and rhythmic stimulation upon hypothalamic neurons
      responding to the 1st excitatory phase of lateral vestibular nucleus stimulation,
      were studied. The data obtained show that activation of some hypothalamic neurons
      following stimulation of the lateral vestibular nucleus has a monosynaptic
      character. The findings suggest that ascending afferents from the lateral
      vestibular nucleus to the hypothalamus pass via oligo- as well as polysynaptic
      pathways.

PMID- 9541957
TI  - [Electrophysiological analysis of interaction between the neuron populations of
      pons and medulla participating in inhibition of the motor activity].
AB  - Neurons of cuneiform, subcuneiform, medial parabrachial, median raphe nuclei were
      studied. 26-47% units were found to send monosynaptic inputs to the raphe magnus
      nucleus, gigantocellular reticular and ventral reticular nuclei. 17-43% responded
      to stimulation of the inhibitory brain stem areas with excitatory-inhibitory
      reactions. Reciprocal distribution projections among inhibitory brain stem areas,
      were found.

PMID- 9541958
TI  - [Changes in EEG induced by prolonged hyperventilation in humans].
AB  - The data obtained revealed a significant augmentation of the EEG slow-wave
      activity following a 32-minute hyperventilation in neurologically healthy
      subjects. In 43% of the subjects, on the 8th minute of the hyperventilation a
      generalised paroxysm of the delta-activity occurred.

PMID- 9541959
TI  - [Effect of RB-101, inhibitor of enkephalin degrading enzymes, on recovery of
      conductivity of the injured sciatic nerve in rats].
AB  - A dose-dependent effect of the enkephalinase RB-101 on functional recovery of the
      rat injured sciatic nerve was revealed. The findings suggest the enkephalines
      participation in regulation of regenerative processes in peripheral nerves.

PMID- 9541960
TI  - [Calcium current and GABA(B) receptors in dorsal sensory cells of the lamprey
      spinal cord].
AB  - GABA and GABAB receptor agonists were shown to reduce the peak calcium current
      amplitude with its subsequent recovery, whereas glycine and taurine, the GABAA
      receptor agonists, did not modify the current. The findings suggest that the
      GABAB receptors mediate a presynaptic inhibition by suppression of the Calcium
      currents in the cyclostome spinal cord.

PMID- 9541962
TI  - [Auto-induced tolerance of the myocardium to ischemia].

PMID- 9541961
TI  - [Effect of baclofen on calcium channel currents in dorsal sensory cells of the
      lamprey spinal cord].
AB  - delta-Baclofen reduced the peak amplitude of the barium current in the DSCs from
      Lunicuspis and L.fluviatilis. The membrane conductance was not altered either by
      baclofen or GABA. The reducing effect could be abolished with delta-aminovaleric
      acid or 2(OH)saclofen. The data obtained suggest presence of the GABAB receptors
      in the DSC membranes. Functional role of the GABAB receptors in primary afferent
      cells of cyclostomes, is discussed.

PMID- 9541963
TI  - [Study of the central and peripheral mechanisms in enhancement of arterial
      baroreflex in cats during noradrenaline infusion].
AB  - An increased suppression of electrical activity of the cardiac inferior nerve by
      the baroreflex during norepinephrine infusion can be eliminated by a preliminary
      infusion of monoamine. The data obtained corroborated our previous findings that
      an increase in arterial pressure due to norepinephrine infusion was essential for
      catecholamine increasing the baroreflex inhibition of electrical activity in
      sympathetic nerves.

PMID- 9541965
TI  - [Cold adaptation and thermoregulatory response to slow and fast cooling].

PMID- 9541964
TI  - [Peptide modulation of vagal sinus arrhythmia in cats].
AB  - In anesthetised cats, following vagal stimulation with short bursts of pulses, a
      narrow zone was identified within the cardiac cycle where even a small change of
      the vagal burst position produced sharp alterations in the magnitude of the
      chronotropic effect. Somatostatin diminished the size of this zone whereas its
      antagonist exerted an opposite effect.

PMID- 9541966
TI  - [Seasonal changes in the composition and functions of myosin filaments of the
      skeletal muscles of ground squirrels Citellus undulatus during hibernation].
AB  - The ability of hibernating and arousing ground squirrels' myosins to bind the key
      enzyme of glycolysis was found to be significantly lower than that of active
      animals. The findings suggest considerable changes in the myosin heavy and light
      chain composition occurring during hibernation, as well as a major contribution
      of the myosin in inhibiting the contractile ability of the skeletal muscles
      during hibernation.

PMID- 9541967
TI  - [Absorption of glucose and glycine in the small intestine of pigs in the presence
      of sodium nitrate].
AB  - Daily perfusion of the pig small intestine with the sodium nitrate solution
      entailed a 2-3-fold drop in absorption of glucose and 1.5-2.0-fold drop in
      absorption of glycine. The sodium nitrate solution being substituted with saline,
      the absorption of both substances recovered by approximately 80%. The toxic
      effect of sodium nitrate seems to be due to both the local effect upon the small
      intestine mucosa and the general effect upon the organism.

PMID- 9541968
TI  - [The role of "growth" domain of urokinase in migration of smooth muscle cells].
AB  - The recombinant urokinase plasmogen activator (r-uPA) activated migration of the
      smooth muscle cells whereas the uPA mutant containing an altered growth factor
      like domain (GFD) was ineffective. The uPA seems to possess properties of the
      urokinase receptor antagonist.

PMID- 9541970
TI  - [Apoptotic cell death of F9 mouse embryonal teratocarcinoma depends on cell
      population density].
AB  - Apoptosis, or programmed cell death, is an active process fundamental to the
      development and homeostasis of multicellular organisms. Mouse embryonal carcinoma
      F9 cell line was shown to express wild type p53 protein known to be one of the
      major regulators of apoptotic cell death. Herein we describe apoptosis-inducing
      conditions for F9 cells. The density reached by a cell population in culture is
      shown to be a factor of apoptotic death for both undifferentiated and induced to
      differentiation F9 cells. However, the relationships between population cell
      density and apoptosis induction are different in undifferentiated and
      differentiating cells.

PMID- 9541971
TI  - [Effect of mycoplasma contamination of the human uterine leiomyosarcoma cell line
      SK-UT-1B on karyotype structure].
AB  - The karyotypic variability has been investigated for human uterine leiomyosarcoma
      cell line SK-UT-1B, cultivated for 30-90 days after contamination with
      Acholeplasma laidlawii, strain PG-8. The character of cell distribution for
      chromosome number gradually changes in contaminated cells, comparatively to the
      control, with the lengthening of the term of contamination. So, in 30 days the
      analysed distributions do not differ in the experimental and in the control
      variants, the modal number of chromosomes being equal to 46. In 60 days the
      frequency of cells with modal number of chromosomes have a tendency to decrease,
      and the range of variability in the number of chromosomes tend to increase. In 90
      days, the frequency of cells with modal number of chromosomes decreases
      significantly, and the range of variability on the number of chromosomes
      increases significantly. The number of chromosomal aberrations gradually
      increases in contaminated cells, as compared to the control, with the lengthening
      of the term of contamination. So, in 30 days the number of chromosomal
      aberrations does not increase, only the number of dicentrics (telomeric
      associations) has the tendency to increase. In 60 days, the number of chromosomal
      aberrations, mainly dicentrics, increases significantly. In 90 days, the number
      of chromosomal aberrations increases significantly, including both dicentrics and
      chromatid breaks. The possible reasons of the observed character of karyotypic
      variability is discussed. Our previous results make it possible to suppose that
      the increase in the number of dicentrics in "markerless" line SK-UT-1B with long
      term contamination may be an additional evidence on the role of dicentrics in
      cell adaptation to in vitro conditions in such lines.

PMID- 9541969
TI  - [Study of the efficacy of prostaglandins and prostacyclin in decrease of osmotic
      permeability of the frog urinary bladder].
AB  - Washout of autacoids using a repeated change of serosal Ringer solution of the
      frog urinary bladder was accompanied by a pronounced rise in the osmotic water
      permeability. A decrease in the osmotic water permeability was achieved by
      addition at the serosal Ringer solution of different eikosanoids at
      concentrations of 10(-10)-10(-6) M. According to efficiency of the recovery of
      the low osmotic water permeability, the substances studied showed the following
      order: prostaglandin E1 > prostaglandin > E2 > prostaglandin F2 alpha >
      (prostaglandin I2). The data obtained indicate a role of the endogenous
      prostaglandin production in maintaining of the low osmotic water permeability.

PMID- 9541972
TI  - [Structural differentiation of dissociated skeletal embryonal myocytes of frog
      under conditions of cell culture].
AB  - The development of membrane structures, providing E-C coupling, and the
      contractile apparatus organization were investigated in frog skeletal myocytes
      cultured for 1 to 10 days in conditions preventing both myocyte division and
      fusion. Ruthenium red was used to determine the membranous structures being in
      contact with the extracellular environment. The marked membrane structures
      (vesicles and short tubules) appeared to be near the cell membrane on the first
      days of culturing. The increase in the ratio of the surface area of all internal
      membranous structures, marked by Ruthenium red, to the external membrane area
      with aging was proven by morphometric calculations, that means a progressive
      development. Contractile filaments were found near the cell membrane on the first
      days of development. Bundles of filaments with initial signs of sarcomere
      organization were observed on the 3rd-4th days, and myofibrils with highly
      organized sarcomeres occupied the main part of the sarcoplasm on the 6th day of
      culturing. The triads appeared also on the sixth day, being regularly inserted
      into the sarcomere structure. Degenerative signs in the myocytes (sarcomere
      disorganization and T-tubule swelling) were observed on the 8-10th days, but the
      area occupied by contractile elements was increased. These results show that the
      myocyte fusion into myotubules is not a necessary condition for either sarcomere
      formation, or the formation of all membranous structures providing the E-C
      coupling.

PMID- 9541974
TI  - [Effect of ionizing radiation on the mitotic cycle of rat embryonal cells,
      immortalized by oncogene E1A and transformed by oncogenes E1A and c-Ha-ras].
AB  - A comparative study of recovery of mitotic cycle in gamma-irradiated rat embryo
      fibroblast cells (intact, immortalized with oncogene E1A and transformed with two
      oncogens-E1A and c-Ha-Ras) was made to show eventually no difference in response
      to 5 Gy irradiation of intact and immortalized cells, and, on the other side, to
      demonstrate a great difference in response of immortalized and transformed cells.
      Cells transformed with the two oncogens E1A and c-Ha-Ras appeared to be much more
      resistant to ionizing radiation than intact cells and cells immortalized with one
      oncogene E1A. These data allow to suggest protein p53 tumor-suppressor
      functioning in transformed cells, but not in intact and immortalized cells.

PMID- 9541973
TI  - [Defect of preferential repair of gamma-ray-induced single-strand breaks in
      transcribed and non-transcribed DNA in Cockayne syndrome cells].
AB  - The repair of gamma-ray-induced DNA single-strand breaks in transcribed
      (protooncogene c-myc) and non-transcribed (human satellite III) DNA of normal
      human fibroblasts and fibroblasts obtained from a patient with Cockayne's
      syndrome (CS) has been investigated. A method of alkaline sucrose sedimentation
      was applied besides the Southern hybridization of 32P-DNA, containing sequences
      analysed with total 3H-DNA distributed through sucrose gradient fractions. No
      increase in the induction of DNA single-strand breaks was found in gamma
      irradiated CS fibroblasts, compared to normal human fibroblasts. At the same
      time, an evident defect in the preferential repair of single-strand breaks in c
      myc gene was observed.

PMID- 9541975
TI  - [Effect of inhibitors of mitochondrial oxidative metabolism on Ca-responses
      induced by purinergic agonists and thapsigargin in rat peritoneal macrophages].
AB  - Effects of two metabolic inhibitors, oligomycin and carbonyl cyanide m
      fluorophenylhydrazone (FCCP), on Ca2+ signals induced by purinergic agonists and
      thapsigargin in Fura-2-loaded rat peritoneal macrophages was investigated. 1
      microgram/ml oligomycin or 1 microM FCCP were shown to inhibit 200 microM ATP or
      200 microM UTP-evoked Ca2+ entry in macrophages. Independently of their chemical
      structure and site of inhibition, both metabolic poisons also inhibit the store
      dependent or "capacitative" Ca2+ influx stimulated by emptying the intracellular
      Ca2+ stores with endoplasmic Ca(2+)-ATPase inhibitor thapsigargin (0.5 microM).
      These data are compatible with the important role the energy level of the cell
      plays in the control of Ca2+ entry in rat peritoneal macrophages.

PMID- 9541976
TI  - [One of the possible ways of propagation of the unicellular parasites Sarcocystis
      muris in the musculature of the intermediate host].
AB  - 20 laboratory mice (Mus musculus) were fed each a single dose of 20,000
      Sarcocystis muris sporocysts to be then sacrificed 1, 2.5, 4, 6 and 10 months
      following infection (p.i.). A visual infection of the murine corps demonstrated
      that the number of sarcocysts per animal increased regularly as the time of
      infection was progressing, being eventually higher after 6 and 10 months p.i.
      than within 1-4 months p.i. This phenomenon was poorly understood from the
      knowledge that the tissue cysts (sarcocysts) are able to increase in size, rather
      than in number, and that the original number of sarcocysts largely depends on the
      number of precystic merozoites available. In our experiments, each of 20 mice was
      fed an equal number of sporocysts, and thus the number of precystic merozoites
      ought to be expected also more or less equal. EM investigation of murine skeletal
      muscles 6 and 10 months p.i. revealed, along with numerous normal sarcocysts, the
      presence of some separate, individual zoites, both within and outside the muscle
      fibre, in the endomysium. Besides, a colony of zoites, living freely without any
      visible common wall, was detected within a muscle fibre adjacent to another one,
      containing a sarcocyst of normal structure. These zoites may have originated from
      one or more sarcocysts, whose cyst walls were spontaneously broken, time after
      another, and thus led the cyst cells go out. These discharged zoites could either
      perish, being enzymatically degraded, or penetrate the neighbouring muscle fibres
      to proceed their further development. The colony making zoites were confined to
      two cell types only: the intermediate cells and the merozoites (gamonts). No
      metrocytes were recognized due, presumably, to inability of these little
      differentiated cells, devoid of penetrative organelles, to invade the host muscle
      cell. The colony of zoites turned out to be a developing population of live
      cells, able to destroy progressively the harbouring muscle fibre, except its
      basal membrane and sarcolemma. It does not seem unlikely that the outer coverings
      of the infected cell could be transformed eventually into a cyst wall to make,
      thus, a new sarcocyst. The above phenomena have never been found in murine
      muscles earlier than 6 months p.i. Although these facts are few and far between,
      they may prompt a possible mechanism of sarcocyst increase in number, in the
      intermediate host with age, even without any additional sporocyst contamination.

PMID- 9541977
TI  - [Use of the magnitude of the histone-DNA ratio as a criterion for evaluating the
      functional activity of the cell genome].
AB  - Cytophotometry was used to demonstrate, on a variety of experimental models, that
      changes in the histone/DNA ratio after staining the cell nucleus (Feulgen, DNA)
      and histones (naphthol yellow S) reflect alterations in the cell functional
      status. This ratio may thus be used as a criterion for evaluation of cell genome
      functional activity which is needed in various biological and medical problems.

PMID- 9541978
TI  - [Fractures of the lower cervical spine. Surgical methods and long-term outcome].
AB  - Between 1980 until 1996 we operated altogether 327 patients because of a
      discoligamentous or osseous injury of the lower cervical spine. In a
      retrospective examination we evaluated the type of the injuries, the mechanism of
      the accidents, the neurological status on admission and the postoperative result.
      With regard to the long-term results we re-investigated 170 patients who have
      been operated on in our Department of Neurosurgery. In none of the patients we
      could find a neurological deterioration after the operation. The prognosis for
      patients with an incomplete and complete transversal syndrome is worse concerning
      a regression of the neurological deficit. The ventral spondylodesis in the
      technique according to Cloward-Crock, Robinson and Smith and Bailey-Badgley with
      ventral plate fixation provided the best results and we recommend these
      techniques for injuries of the lower cervical spine.

PMID- 9541979
TI  - [Isolated traumatic dislocation of the radial head in children. Case reports,
      differential diagnosis and review of the literature].
AB  - Isolated dislocations of the radial head in children without fracture of the ulna
      are an extremely rare injury. The diagnosis is easily missed. This leads to
      permanent deformity of the elbow; on the other hand prompt treatment restores a
      normal anatomical and functional elbow. Fourteen patients and their long-term
      outcome are presented.

PMID- 9541980
TI  - [Studying minimally invasive osteosynthesis methods for distal radius fractures.
      Intra-focal vs. conventional wire osteosynthesis].
AB  - From 1992 to 1995 126 patients were treated with percutaneous wire pinning. Sixty
      one patients were treated by Kapandji's technique and 65 patients were treated
      conventionally. Forty-nine patients were examined by 3 different scores (Cooney,
      Castaing, Stewart). The analysis of the scores showed no differences between the
      Kapandji technique and the conventional method. Functional and radiological
      results showed no correlation. Furthermore we found out that the results depend
      on the score. We conclude that the Kapandji technique shows no benefit in
      comparison to the conventional method. Functional and radiological results are
      not divisible: a conclusion from X-ray to function and vice versa is not allowed.
      A comparison of results is senseless if someone does not use the same score.

PMID- 9541981
TI  - [Method for measuring the comparative stability of osteosynthesis in the dorsal
      pelvic ring].
AB  - In the past, biomechanical investigations on the dorsal pelvic ring have
      generally been performed on a small number of cadaveric pelves in various non
      standardized procedures. Significant differences in stability between different
      internal fixation methods of unstable pelvic ring fractures were not found. The
      experimental design presented here was based as closely as possible on the
      physiological loading of the pelvis in one-leg stance. This method made it
      possible to carry out standardized, reproducible tests on different osteosytheses
      of the sacroiliac joint. Furthermore, the suitability of artificial bones for
      such investigations can be assessed on the basis of a larger number of similar
      experiments on artificial and human pelves and the number of human pelves
      required for such studies could be reduced.

PMID- 9541982
TI  - [Occasional alcohol drinkers and chronic alcoholics. Comparison of two patient
      groups from the viewpoint of accident surgery].
AB  - Patients who suffer an accident after alcohol consumption can be differentiated
      into 2 groups: patients which drink alcohol occasionally and chronic alcoholics.
      We examined prospectively in-patients treated after suffering a trauma in an
      alcoholised state. The diagnosis acute alcohol intoxication was made by a breath
      alcohol-analysis, the diagnosis chronic alcoholism by a shortened MAST-test. In
      the average chronic alcoholics were 12 years older than acute intoxicated. Family
      background of chronic alcoholics was more often disrupted and social status lower
      than in acute alcoholics. For the acute alcoholics a car crash, for the chronic
      alcoholics a fall was the main trauma cause. In over 50% both patient groups
      suffered a minor head injury. Chronic alcoholics had a twice as long hospital
      stay (16.1 +/- 3.2 vs. 8.5 +/- 1.1 days), needed more specialist consultations
      (84% vs. 60%) and developed more complications (40% vs 16%) than the acute
      alcohol intoxicated. The ISS (Injury Severity Score) was the same for both
      patient groups (6.7 +/- 0.7 vs. 7.1 +/- 0.8) and had no prognostic value for the
      group of the chronic alcoholics. On the basis of the present findings it is
      advisable to check the diagnosis alcohol intoxication and to look whether chronic
      alcoholism is present whenever a drunken patient is admitted.

PMID- 9541983
TI  - [Fracture of the odontoid process in primary myelopathy. Report of a case].
AB  - Fractures of the odontoid are reported to contribute in 15% to cervical spine
      fractures. The clinical findings range between no symptoms at all and sudden
      death. Neurological deficits are seen in 6 to 25% of these patients. The overall
      mortality in this group is 3 to 8%. Fractures of the odontoid process combined
      with primary myelopathy has been reported seldom. We describe a traumatic
      fracture of the odontoid process with primary myelopathy, the chosen therapy and
      the follow-up.

PMID- 9541984
TI  - The gross anatomy of the cranial cervical ganglion and its branches in the
      Bactrian camel (Camelus bactrianus).
AB  - Ten specimens of the head and neck of the Bactrian camel (Camelus bactrianus)
      were dissected to study the situation, arrangement and branches of the cranial
      cervical ganglion (ganglion cervicale craniale). The ganglion was a greyish
      fusiform structure, averaging 15-20 mm in length, 4-6 mm in width and 3 mm in
      thickness, located on the rostro-lateral surface of the longus capitis and
      covered by the mandibular gland. The branches of the cranial cervical ganglion
      included the internal carotid nerve, external carotid nerve, jugular nerve and
      the branches connecting with the glossopharyngeal, vagus, hypoglossal and first
      cervical nerves.

PMID- 9541985
TI  - Chickens hyperimmunized with Escherichia coli J5 strain are protected against
      experimental challenge with Escherichia coli O78 serotype.

PMID- 9541986
TI  - Normal haematopoiesis, cellular components and stainable iron content in the bone
      marrow of camels (Camelus dromedarius).
AB  - Bone marrow samples were collected from the ribs of 20 healthy adult male Iranian
      camels (Camelus dromedarius). The bone marrow smears were stained using Wright's
      stain. Blood samples were collected at the same time for routine haematological
      examination. The development and morphology of the blood cells in the bone marrow
      of the camels were similar to those of other domestic species. The mean
      myeloid/erythroid ratio was 1.21, the mean erythroid percentage was 42.7% and the
      mean myeloid percentage was 52.0%. The mean percentage of other cells was 5.3%.
      The mean percentage of eosinophils in the myeloid series was higher than in other
      domestic species. Iron stores, estimated from Perl's stain, ranged from scant
      (1+) to moderate (3+) but most samples had 2+ iron content. All peripheral blood
      results were within reference ranges.

PMID- 9541987
TI  - Cytogenetic alterations in four feline soft-tissue tumours.
AB  - Four mesenchymal neoplasms (two malignant fibroblastic histiocytomas, one
      fibrosarcoma, one fibroma) were investigated cytogenetically. Although no
      specific alterations were present, the frequent nonrandom involvement of
      chromosome E1 became clearly evident. Karyotypic alterations involving unrelated
      clonal changes were also present in the fibroma.

PMID- 9541988
TI  - Nitric oxide causes the macroschizonts of Theileria annulata to disappear and
      host cells to become apoptotic.
AB  - The proliferation of Theileria annulata macroschizont-infected cell lines in
      vitro was significantly inhibited by nitric oxide (NO) generated by S-nitroso-N
      acetyl-DL-penicillamine (SNAP). Incubation with SNAP caused the macroschizonts to
      disappear and host cells to become apoptotic. SNAP-derived NO also significantly
      inhibited the incorporation of tritiated thymidine by cultures of cells in which
      the schizonts had been induced to differentiate into merozoites by maintenance at
      41 degrees C instead of 37 degrees C, the temperature used for culturing
      macroschizont-infected cells. These results point to NO as the mediator of
      macrophage anti-T. annulata activity and provide new evidence that the protective
      immune mechanisms which allow cattle to recover from primary infection and resist
      challenge may be attributed principally to the products of activated macrophages.
      These findings indicate that effective inactivated vaccines against T. annulata
      should include antigens able to stimulate the type of CD4+ T cell response which
      elicits macrophage activation and NO synthesis.

PMID- 9541990
TI  - The disposition kinetics, urinary excretion and dosage regimen of amikacin in
      cross-bred bovine calves.
AB  - The disposition kinetics, urinary excretion and dosage regimen of amikacin after
      a single intravenous administration of 10 mg/kg was investigated in six cross
      bred bovine calves. At 1 min, the concentration of amikacin in the plasma was
      116.9 +/- 3.16 micrograms/ml and the minimum therapeutic concentration was
      maintained for 8 h. The elimination half-life and volume of distribution were
      3.09 +/- 0.27 h and 0.4 +/- 0.03 L/kg, respectively. The total body clearance
      (ClB) and T/P ratio were 0.09 +/- 0.002 L/kg/h and 4.98 +/- 0.41, respectively.
      Approximately 50% of the total dose of amikacin was recovered in the urine within
      24 h after administration. Amikacin in concentrations ranging from 5 to 150
      micrograms/ml bound to plasma proteins to the extent of 6.32% +/- 0.42%. A
      satisfactory intravenous dosage regimen of amikacin in bovine calves would be 13
      mg/kg followed by 12 mg/kg at 12 h intervals.

PMID- 9541991
TI  - Preliminary observations on the pharmacokinetics of CDRI compound 81/470 in
      calves.

PMID- 9541989
TI  - The effect of copper deficiency on the peripheral blood cells of cattle.
AB  - Six female cattle were given molybdenum (30 ppm) and sulphate (225 ppm) to induce
      experimental secondary copper deficiency. The total and differential leukocyte
      numbers and lymphocyte subpopulations were counted and the neutrophil activity
      was assessed by means of nitroblue tetrazolium reduction and phagocytosis of
      sheep erythrocytes. The serum caeruloplasmin activity and concentration were also
      determined. Copper deficiency was confirmed from decreased serum copper levels,
      the animals with values less than 5.9 mumol/L being considered deficient. Total
      leukocyte numbers were not affected by the copper deficiency. However,
      differential counts showed a marked increase in monocyte subpopulations, a
      significant decrease in B lymphocytes and reduced neutrophil activity. The serum
      caeruloplasmin activity was decreased about 50%, but the total serum protein
      concentration was less altered. We concluded that the effect of these changes on
      the animals' immune competence may contribute to a greater incidence of
      infectious diseases in copper-deficient cattle.

PMID- 9541992
TI  - [Principles of a canteen feeding organization of railway transport workers in
      repair-restorative work in regions polluted with radiation].
AB  - Dietary intake and actual food consumption of the railway transport workers are
      employed in repair in radioactive polluted regions. Disbalance of dining rations
      and deficiency in vegetable fat, some mineral elements and vitamins was
      established. For the correction of revealed defects the methodological
      recommendations for organization of a canteen feeding of the workers of railway
      transport was developed.

PMID- 9541993
TI  - [Taurine and carnosine in tissues of Pacific mollusks].
AB  - The containing of taurine and carnosine (low-molecular biologically active
      substances) was studied in tissues of molluscs (Gastropodae, Brahiopodae and
      Cephalopodae) by 38 species. The highest concentration of taurine found in the
      octopus and 5 species of shells (Gastropodae). The containing of carnosine in
      mollusks is highly lower than in bovine muscles. Organoleptic quality of
      lyophilized water-spirit extracts by soft tissues of molluscs allow to use it as
      a taurine-enriching food addition.

PMID- 9541994
TI  - [Effect of l-carnitine on the expression of glycine conjugates in rats in
      experimental B2-hypovitaminosis].
AB  - The dynamic of glycine conjugates excretion in riboflavin deficient (RFD) rats
      was studied. The excretion of isovaleryl-, n-butyryl-, isobutyryl-,2-Me-butyryl-
      and hexanoylglycines by the RFD rats considerably increased from 1 week of the
      experiment and reached a plateau after 5 week. Under L-carnitine supplementation
      the acylglycines (isobutyryl- and isovaleryl) as well as some organic acids
      excretion was diminished.

PMID- 9541996
TI  - [Comparative characteristics of the composition and food value of Russian and
      imported canned meat for child nutrition].
AB  - In the present review the brief features of main groups of domestic and foreign
      canned food are given. The special attention is paid to them ingredients and food
      value, which are decisive determinants at choice one or another kind of canned
      food for children.

PMID- 9541995
TI  - [Dihydroquercetin--a new antioxidant and biologically active food additive].
AB  - Information about types of vegetative raw material for flavonoid dihydroquercetin
      manufacture are given. Data of a wide spectrum of biological activity of
      dihydroquercetin are systematized. Two directions of use dihydroquercetin in food
      industry: as antioxidant and as biologically active supplement for creation
      different types of parapharmaceutical production is shown. Dihydroquercetin in
      the capacity of antioxidant may be compared or exceeds many synthetic and natural
      antioxidants and, in particular, known bioflavonoids (quercetin). High
      antioxidant activity of dihydroquercetin is combined with absence embryotoxicity,
      teratogenicity, allergenicity and mutability. Dihydroquercetin used as efficient
      antioxidant with regard to vegetable oils, animal fat, milk powder, fat contain
      pastry. Parapharmaceutical production with dihydroquercetin is intended for
      prophylactic of "oxidative stress" diseases (cardiovascular, bronchopulmonary,
      etc.). Practical application of new types of products containing dihydroquercetin
      was described. Dihydroquercetin is an available commercial food additive,
      producing domestic industry.

PMID- 9541997
TI  - [Content of toxic substances in breast milk after timely and premature labor].
AB  - Data on the contents of protein, fats and toxic compounds (PCB, DDT, gamma
      Lindane) in breast milk Russian and Vietnamese women after timely and premature
      childbed are resulted. The contents of protein in transitive milk was higher than
      in mature milk, both timely childbed and premature one. The contents of protein
      in nature milk of the Vietnamese women was lower, than in mature milk of the
      Russian women (12 g/l against 16.5 g/l accordingly). The contents of fat in
      breast milk of the Russian women in lactation increased. Vietnamese women had
      very low fat level in mature milk (29 g/l against 42 g/l at the Russian women).
      The contents of toxic compounds (PCB, DDT, gamma-Lindane) in breast milk both,
      Vietnamese women and Russian women was rather high and significant frequency of
      detection of these compounds in milk was marked. The correlation contents of
      basic food components in breast milk and level of toxic compounds was absent.

PMID- 9541998
TI  - [Parenteral nutrition in the pre- and early postoperative periods. Unsolved
      problems and contradictions].
AB  - The analysis of early published and own clinical investigations dedicated study
      of parenteral nutrition in pre- and early postoperative periods was represented.
      Special attention was paid to contradictory conclusions being result of these
      investigations. The recommendations were given about cases when it is necessary
      to apply the parenteral nutrition in pre- and early postoperative periods, and
      when it is necessary to refuse it.

PMID- 9541999
TI  - [Change in various parameters of metabolism in the early postoperative period in
      artificial and "traditional" probe nutrition].
AB  - The problems of enteral and parenteral nutrition of patients with gastroenteric
      diseases, peritonitis in early postoperative period are considered. A degree of
      efficiency of specialized food mixes as one of the forms of basic therapy of a
      number of surgical and therapeutic of diseases is shown.

PMID- 9542000
TI  - [Topinambur concentrate in the treatment of patients with insulin-dependent
      diabetes mellitus].
AB  - The authors studied activity of home nutricevtic concentrate of topinambur in
      patients with different clinical forms of insulin-dependent diabetes mellitus.
      Concentrate of topinambur promoted normal carbohydrate and lipid metabolism,
      increased ferrum level in serum, had immunomodulating activity. Nutricevtic was
      the most effective one in patients with not long duration of insulin-dependent
      diabetes mellitus.

PMID- 9542001
TI  - [Nutrition and drugs. II. Biotransformation, interactions].
AB  - The problem of interaction of drugs and food substances in a human organism is
      discussed. The influence of dietary factors on the drugs metabolism is
      considered. The special attention is paid to possible negative effects of
      interaction of food and drugs.

PMID- 9542002
TI  - [From nutrition science to the practice of health nutrition. Sixteenth
      International Congress on Nutrition in Canada].

PMID- 9542003
TI  - [The nerve supply of the knee joint].
AB  - The paper presents the present state of research on the most important receptors
      of joints and muscles with regard to occurrence, structure, and function.
      Proprioception relies on the nervous supply of the tissues in the knee joint, and
      on the surrounding muscles and tendons; it is the basis of coordination.

PMID- 9542004
TI  - [The knee joint--imaging].
AB  - In the assessment of knee joint abnormalities plain films must still be used
      today as primary imaging modality. For soft tissue, cartilage, tendon and
      ligament lesions, sonography, CT and MRI (with arthrography) is available today.
      Especially MRI leads to a significantly extended diagnosis.

PMID- 9542005
TI  - [Indications and surgical procedures in meniscus and capsular ligament injuries].
AB  - The main aim in the treatment of meniscus injuries is the restoration of the
      meniscus by a primary suture. Partial resections of the meniscus should be done
      in a sophisticated arthroscopic technique. By the reason of relaxing of the
      joint's ligament should be repaired by operation. In spite of a larger "defect"
      bone-tendon-bone techniques are to prefer because of an improved long-term
      stability.

PMID- 9542006
TI  - [Therapeutic physical training after knee injuries].
AB  - Exercise training is a therapy that accompanies and follows physiotherapy. Basic
      training principles are discussed on the basis of motricity research. Initially,
      exercise therapy mostly trains patients to recall and standardize the execution
      of exercise programs. With the patient's increasing power of endurance, the
      intensity of extent of training are increased. Exercise therapy eventually aims
      at particularly preparing the patient for the activities of daily living and the
      sportsman for the requirements specific to training and competition.

PMID- 9542007
TI  - [Treatment with physical therapy after knee injuries].
AB  - Trauma to the inner knee disturb the organism's local and central regulations.
      Physiotherapeutic measures stimulate self-regulatory and self-regenerative
      mechanisms of the organism. Depending on the specific needs of the patient,
      active exercise treatment, or various procedures of physical therapy are
      administered (hydro and thermotherapy, electromedicine, light therapy, aerosol
      therapy, balneology, and climatology) in order to achieve his/her full
      restoration to the maximal potential vocationally, socially, and physically.

PMID- 9542008
TI  - Optimizing urography.
AB  - Urography is regarded as one of the best screening tests for evaluation of
      urinary tract disease and is commonly used in the search for a cause of hematuria
      or the presence of upper tract urothelial masses. It is also used in the
      evaluation of patients with trauma, known or suspected urolithiasis, or renal
      infection and for the documentation of obstruction or congenital abnormalities.
      The physician should have a basic understanding of iodinated contrast media and
      their benefits and effects on the patient. Patient risk factors include a history
      of (1) renal impairment, (2) significant allergies, (3) asthma, (4) diabetes
      mellitus, and (5) cardiac disease (particularly congestive heart failure,
      arrhythmias, unstable angina, recent myocardial infarction, and primary pulmonary
      hypertension). Changing options for imaging modalities, contrast media, and
      patient preparation require continued attention to detail and individualization
      to allow optimization of the urographic examination.

PMID- 9542009
TI  - Current roles and controversies in the imaging evaluation of acute renal
      infection.
AB  - The current roles and controversies in imaging of the kidneys for the evaluation
      of patients with acute renal infection are reviewed. The nomenclature used in
      describing the extent of the renal imaging findings in acute pyelonephritis
      suggested by the Society of Uroradiology to help avoid confusion in terminology
      in the past literature is briefly described. Computed tomography (CT) is superior
      to urography and renal sonography for the evaluation and management of adults
      with acute renal infection. [99mTc]-dimercapto succinic acid (DMSA) cortical
      scintigraphy is the imaging study for the evaluation of children with acute
      pyelonephritis investigated by some, although power Doppler ultrasound, and even
      CT, can be considered as a possible alternative.

PMID- 9542010
TI  - Noncontrast helical CT for ureteral stones.
AB  - Noncontrast helical computed tomography (CT) has recently been found to be
      superior to excretory urography (IVU) in the evaluation of patients with
      suspected ureterolithiasis. Noncontrast helical CT does not require the use of
      intravenous contrast material with its associated cost and risk of adverse
      reactions and can be completed within 5 min, in most cases. Noncontrast CT often
      detects extraurinary pathology responsible for the patient's symptoms. CT is also
      more sensitive than IVU in detecting the calculus, regardless of its size,
      location, and chemical composition. However, confidently differentiating ureteral
      calculi from phleboliths along the course of the ureter may, at times, be
      difficult. The "tissue-rim" sign, a rim of soft tissue attenuation around the
      suspicious calcification, is helpful in making this distinction. Noncontrast CT
      does not provide physiological information about renal function and the degree of
      obstruction. A pilot study has suggested a proportional relationship between the
      extent of perinephric edema and the degree of obstruction. The cost of the
      examination and the radiation dose delivered to the patient may be higher with
      CT. Despite these limitations, noncontrast helical CT has quickly become the
      imaging study of choice in evaluating patients with acute flank pain.

PMID- 9542011
TI  - Magnetic resonance imaging of renal masses.
AB  - Renal cancer is diagnosed in 27,000 Americans and accounts for 12,000 deaths per
      year. Fortunately, improvements in imaging technology have resulted in earlier
      detection and longer survival. Although computed tomography (CT) and ultrasound
      (US) have accounted for much of this success, magnetic resonance (MR) imaging can
      offer several improvements in renal cancer imaging. MR imaging has demonstrated
      increased detection of tumor thrombus in the renal vein and IVC with better
      delineation of the superior extent of the tumor thrombus in the IVC, especially
      in the region of the right atrium. This information potentially impacts the
      surgical approach in cases where CT or US is equivocal. Visualization of tumor
      extension to the liver, spleen, and psoas muscle is also improved with MR
      imaging, increasing staging accuracy in selected cases. In addition, because of
      the relatively low nephrotoxicity and allergic potential of gadolinium chelates,
      contrast-enhanced MR imaging remains the study of choice for patients who cannot
      tolerate iodinated contrast agents. Although the current role of MR in renal
      cancer imaging is complementary to that of CT and US, its future role has not yet
      been completely defined. Recent developments in rapid MR imaging techniques have
      suggested the possibility of improved detection and characterization of renal
      masses relative to CT. In addition, as MR spectroscopic imaging of the kidney
      evolves, the possibility of future identification and characterization of renal
      masses on a biochemical basis may provide completely new insight into our
      understanding of renal cancer.

PMID- 9542012
TI  - From needles to numbers: can noninvasive imaging distinguish benign and malignant
      adrenal lesions?
AB  - Adrenal masses are a relatively common finding on computed tomography (CT) and
      magnetic resonance imaging (MRI). Until recently, adrenal biopsy, resection, or
      clinical follow-up were the only methods of distinguishing benign adenomas from
      malignancies. On the basis of their higher lipid content, adenomas have
      characteristics appearances on CT and MRI that can be used to separate them from
      non-lipid-containing lesions such as metastases. CT densitometry with or without
      contrast media and chemical shift MRI (CSI) are two examples of techniques with
      adequate sensitivity (50-90%) and excellent specificity (> 95%) for adrenal
      adenomas. While the need for invasive tissue sampling is reduced because of these
      techniques, it is eliminated because lesions not meeting the criteria for
      adenomas are not always malignant. However, CT densitometry and CSI are likely to
      reduce significantly the need for histology sampling of incidentally discovered
      adrenal masses due to the high specificity of these new techniques.

PMID- 9542013
TI  - Color-flow and power Doppler imaging of the testes.
AB  - The development of color-flow imaging has made ultrasound the primary imaging
      modality for the evaluation of testicular pathology. The ability to distinguish
      between epididymo-orchitis and torsion is of great clinical significance in those
      patients with acute onset of pain. Not only does the appropriate treatment depend
      on the correct diagnosis, but the outcome following that treatment is also
      dependent on establishment of the diagnosis. Although it is of less importance in
      the evaluation of testicular neoplasms, color-flow imaging does provide
      adjunctive information that can aid in establishment of the proper diagnosis in
      confusing clinical situations. The diagnosis of varicocele depends on color-flow
      imaging, and the prediction of testicular viability following trauma is essential
      for proper treatment. More studies concerning the use of power Doppler for
      imaging of scrotal disorders are necessary to determine what its role will be.

PMID- 9542014
TI  - Color and power Doppler imaging of the kidneys.
AB  - Sonography is a widely used modality for the evaluation of both native and
      transplanted kidneys. It is noninvasive, portable, and requires minimal patient
      preparation. Renal sonography can estimate kidney size, determine the presence or
      absence of hydronephrosis, and the presence and characteristics of any intrarenal
      or extrarenal masses. The addition of color, and, more recently, power Doppler
      have enhanced the diagnostic capabilities of renal sonography. Color and power
      Doppler have distinct but complementary uses, and knowledge of the advantages and
      limitations of each are essential for proper application of these powerful tools.
      The differences between color and power Doppler is discussed, with emphasis on
      their relative strengths. Clinical uses of color Doppler include the evaluation
      of perfusion abnormalities, renal artery stenosis, renal vein thrombosis,
      pseudoaneurysms, and arteriovenous fistulas. Color and power Doppler are also
      helpful in the evaluation of the transplanted kidney and can suggest the presence
      of transplant rejection. The sonographic color and power Doppler features of
      disease entities which affect the kidneys are discussed. Knowledge of these
      sonographic features will enable prompt diagnosis, thereby expediting patient
      care.

PMID- 9542015
TI  - Pediatric uroradiology--1997.
AB  - The imaging of common pediatric urological problems is in evolution.
      Modifications of standard techniques such as substitution of cyclic voiding
      cystourethrography in the neonate and infants, introduction of newer modalities
      (Doppler ultrasound), and new nuclear renal agents (Tc-MAG3) have enhanced our
      ability to detect anomalies and abnormalities. In this brief article, some of the
      recent developments in imaging are reviewed and the ways in which these
      developments interface with traditional imaging studies are presented.

PMID- 9542016
TI  - Interventional uroradiology.
AB  - The development of interventional uroradiologic techniques has had a major impact
      on the care of the urologic patient by allowing nonoperative treatment of many
      disease processes. This article will review percutaneous nephrostomy with
      emphasis on urologic calculi, interventional therapy for neoplasms and trauma of
      the urinary tract, diagnosis and treatment of renovascular hypertension, and the
      management of complications following renal transplantation.

PMID- 9542017
TI  - Upper urinary tract trauma--current concepts.
AB  - This paper reviews current concepts and controversies in regard to the
      classification, clinical findings, imaging techniques, and management of upper
      urinary tract trauma. The impact of CT, and especially spiral CT, in
      differentiating significant from nonsignificant renal trauma is reviewed. The
      controversy in regard to the correct approach to the management of any
      significant renal trauma (i.e., conservative vs. aggressive therapy) as well as
      the differences in opinion as to the appropriate treatment between blunt and
      penetrating trauma are also reviewed.

PMID- 9542018
TI  - Lower urinary tract trauma.
AB  - This article reviews and illustrates bladder and urethral injuries, including
      their mechanisms of injury, imaging diagnosis, systems for classification, and
      the accuracy/pitfalls of the diagnostic methods. The bulk of this review will
      focus on lower urinary tract injuries caused by high speed, wide impact blunt
      trauma which is the most common mechanism of lower urinary tract injury
      encountered in civilian practice.

PMID- 9542019
TI  - Prostate cancer: the diagnostic dilemma and the place of imaging in detection and
      staging.

PMID- 9542020
TI  - [Revision of the approbation regulation from the viewpoint of a surgical
      teacher].

PMID- 9542021
TI  - [Surgical therapy of benign thyroid gland diseases].
AB  - Operations due to benign thyroid diseases are one of the most common elective
      surgical procedures performed in Germany. In the majority of cases, the
      preoperative determination of the serum thyrotropin concentration and an
      ultrasound of the thyroid region are sufficient preoperative investigations. In
      cases of thyroid functional disorders a scintigram should be additionally
      performed. Indications for operation in nodular goiter are local, mechanical
      compression, suspicion of malignancy and focal or disseminated autonomy. In
      Graves' disease the indication for operation is usually recurrent hyperthyroidism
      after medical treatment. In endemic nodular goiter the morphology of the nodular
      thyroid tissue is the guideline for resection; i.e. all nodules have to be
      removed. In Graves' disease the function of the remaining thyroid tissue is
      essential. The standardized subtotal resection with remaining tissue around the
      hilus, which frequently barries nodules, should be avoided. Instead a selective
      resection which takes the individual morphology and function of the diseased
      thyroid tissue into account should be favorized. With this operative technique
      the surgeon will have frequently direct contact with the recurrent nerve and the
      parathyroids. It is documented, that intraoperative visualisation of the
      recurrent nerve decreases not only the rate of permanent nerve damages but
      increases as well the completeness of resection. Additionally, ligation of the
      inferior thyroid artery decreases the incidence of residual or recurrent disease
      without enlarging the risk of postoperative parathyroiprive hypocalcemia. An
      individual follow-up with iodine and/or thyroxine replacement therapy is an
      indispensable component of the surgical therapeutic approach. The target of
      thyroxine substitution in patients after resection due to benign thyroid diseases
      is a physiologic serum thyrotropin concentration (0.3 to 4.0 mU/l).

PMID- 9542022
TI  - [Postoperative recurrent nerve paralysis after initial interventions for benign
      goiter].
AB  - Between January 1st, 1979 and December 31st 1993, 2501 operations for benign
      diseases of the thyroid gland were performed. The documentation was done
      prospectively. The operation technique remained the same during these years. The
      recurrent laryngeal nerve wasn't routinely identified. All together we saw 0.6%
      permanent vocal cord palsies. The incidence of nerve paralysis was correlated to
      the size (weight), to the expansion of the goiter, to the performed operative
      procedure and to patients' age and gender.

PMID- 9542023
TI  - [Reducing the rate of recurrent nerve paralysis by routine exposure of the nerves
      in thyroid gland operations].
AB  - The retrospective and comparative analysis of 734 benign operations of the
      thyroid gland during the years 1979-1993 without preparation and 1.022 operations
      between 1994 and 1996 with routine preparation of the recurrent laryngeal nerve
      shows a decrease of the permanent palsy rate from 5.99% to 0.88%. In 1996 0.48%
      pareses (2 cases in 410 operations) were seen. OPERATIVE TECHNIQUE: Before
      ligature of the blood-vessels at the hilum and before dorsal mobilisation of the
      thyroid lobe first the inferior thyroid artery and then the recurrent laryngeal
      nerve are identified which is located distally of the artery at the esophago
      tracheal sulcus and is prepared until its entry in the larynx. RECOMMENDATION: We
      advice routine recurrent laryngeal nerve preparation in any operation of the
      thyroid gland. However, absolutely necessary is the identification of the nerve
      in the following situations: 1. Hemithyroidectomy, 2. Exstirpation of dorsal
      nodules of the hilum, 3. Morbus Basedow, 4. Reoperations, 5. Carcinomas.

PMID- 9542024
TI  - [Rate of complications with systematic exposure of the recurrent laryngeal nerve
      and parathyroid glands in operations for benign thyroid gland diseases].
AB  - OBJECTIVE: The influence of the operation technique on the complication rate of
      thyroid operations is still a subject of discussions. In this study, we analysed
      therefore the most important complications, i.e. palsy of the recurrent laryngeal
      nerve and hypoparathyroidism, specially under the aspect of routine exposition of
      the recurrent laryngeal nerve and parathyroids. METHODS: 116 patients with goiter
      operations of the year 1995 (12 different surgeons) were analysed. Age of
      patients was between 7 and 72 years, mean age 45 years. The operations performed
      were 70 subtotal resections (benign goiter), 33 near-total-resections (diffuse
      autonomy or Graves' disease), 33 hemithyroidectomies (scintigraphically "cold"
      nodules), 4 adenoma resections with combinations of these resections in 24 cases.
      RESULTS: 4.3% of the patients (5/116 patients) developed an unilateral recurrent
      nerve palsy immediately after operation. Persisting recurrent nerve palsy
      occurred only in 1.7% (2/116) of these cases. Postoperative nerve palsy was
      mainly found after extensive resections (2/33 near-total-resections) or
      operations of recurrent goiter (2/6 re-operations), rarely after routine
      operations (1/70 subtotal resections). Hypocalcemia was found in 9.5% of the
      patients (11/116), of which 9 cases were asymptomatic (7.8%) and 2 symptomatic by
      tetany (1.7%). Persisting hypocalcemia for longer than one week was found in 3.5%
      (4/116), permanent hypoparathyroidism in 1.7% (2/116) of the patients.
      CONCLUSIONS: Routine systematic exposure of recurrent laryngeal nerves and
      parathyroids reduces the incidence of complications in thyroid surgery to a
      minimum. The risk of recurrent nerve palsy increases with extent and difficulty
      of the operation, with the highest risk for nerve lesions seen in re-operations
      and near-total-resections.

PMID- 9542026
TI  - [Indications and surgical therapy of thyroid gland diseases--analysis of 725
      operated patients].
AB  - Diseases of the thyroid gland are an important part of elective surgical
      procedures. The adequate surgical therapy is at present standardized and requires
      a permanent qualitative control to reduce avoidable complications. The relation
      between men and women in our patients (n = 725) was 1 to 5. The mean age was 51.2
      years. 10% (n = 79) of the patients were hyperthyroid. 646 patients had benign
      disease; and 79 patients were found to have malignancy of the thyroid gland. The
      most common indication for an operation was bilateral multinodular goitre (n =
      325) in combination with a cold nodule (n = 123), in 79 patients latent
      hyperthyroidism or Morbus Basedow (n = 22). Struma nodosa with retrosternal
      extension (n = 49), recurrence of goitre (n = 34), thyroiditis (n = 12) and
      dystopic goitre (n = 2) were rare in these patients. Patients with malignancy of
      the thyroid gland were always treated by thyroidectomy or completed thyroidectomy
      with lymphnode dissection. In the cases of benign disease the surgical methods
      were variable, although the bilateral subtotal resection (n = 413) predominated.
      While doing so the radical resection of parenchyma with a persistent functioning
      remnant of goitre of 5 cm3 was favoured. The resulting postoperative
      complications are discussed. An endocrinological appropriate follow-up of the
      patients is necessary.

PMID- 9542025
TI  - [Incidence of damage to the recurrent laryngeal nerve in surgical therapy of
      various thyroid gland diseases--a retrospective study].
AB  - We investigated the incidence of the recurrent laryngeal nerve (RLN) palsy after
      thyroid gland surgery in 725 cases. The incidence was correlated to the different
      diseases of the thyroid gland, to the operative procedure (subtotal resection,
      lobectomy, thyroidectomy), to the intraoperative exploration of the nerve and to
      the surgeons' state of training. RLN palsy was found in 7.6 per cent (4.8 per
      cent nerve at risk) five days after surgery. A permanent RLN damage was defined
      as a persisting paralysis of the vocal cord six months after surgery. Permanent
      nerve damage occurred in 2.1 per cent for euthyroid nodular goitre, for recurrent
      goitre in 11.7 per cent and for thyroid carcinoma in 10.1 per cent. There was a
      statistically significant difference between the number of RLN pareses occurring
      after nerve exposure with 4.2 per cent and that occurring after non-exposure with
      1.1 per cent for subtotal lobectomy. 67.7 per cent of these pareses at day five
      were transient. The RLN palsy rate for Senior House Officers was 6.7 per cent but
      there where none for registrars and consultants. CONCLUSIONS: The RLN damage five
      days after thyroid gland surgery is mainly caused by the great number of
      recurrent goitre and thyroid cancer (16.1 per cent), the rate of procedures
      performed by younger surgeons and the near total resection of euthyroid goitre.
      The exposure of RLN is important for the training to manage thyroid gland
      surgery.

PMID- 9542027
TI  - [Results of selective goiter resection in functional autonomy].
AB  - In the period from 1989 to 1994 a surgical treatment of toxic nodular goiter was
      performed in 145 patients. An unifocal autonomous adenoma occurred in 69 cases, a
      multifocal disease 76 times. The operative strategy consisted in a bilateral
      resection 105 times, and unilateral resection 29 times. An excision of a single
      node was carried out in ten cases. In one operation a hemithyroidectomy on one
      side and a subtotal resection of the other lobe was done. In May 1996 an
      interrogation about the current thyroid function was performed. In 105 (72.4%)
      patients a re-evaluation was possible. Concerning the postoperative therapy for
      prevention of recurrent hyperthyroidism or goiter growth, 84 patients (80%) had
      been treated with thyroxin and/or iodine. Under this therapy, after a mean period
      of 36 months 94 patients (89.5%) were clinically euthyroid. Nine patients (8.6%)
      were hypothyroid. Two patients developed a recurrent hyperthyroidism. Both of
      them belonged to the group of patients with multifocal autonomies, and both had
      been treated with thyroxin postoperatively. In one case, recurrent goiter growth
      occurred that did not need a therapeutic intervention. This patient as well had
      been treated for a multinodular goiter originally. She had not been taking a
      specific medication postoperatively. We conclude that a functional resection of
      autonomic tissue in nodular goiters is efficient in controlling the thyroid
      metabolism. A medical prophylaxis was not able to prevent recurrent
      hyperthyroidism in two cases.

PMID- 9542028
TI  - [Total thyroidectomy in iodine-deficient goiter--an effective treatment
      alternative?].
AB  - It can be difficult to define the extent of struma resection because of large
      multinodular transformation. The total thyroidectomy of goiter is refused due to
      a supposed increase in complications. A high rate of goiter recurrence together
      with higher risks of complications demonstrates the problems of insufficient
      resection. This study investigates the rate of complications of total
      thyroidectomy of goiter. 4767 surgical treatments (partial thyroidectomy,
      hemithyroidectomy or total thyroidectomy) of goiter were investigated.
      Retrospectively the rate of postoperative complications (hemorrhage, wound
      infection, recurrent nerve palsy, hypocalcemia) after strumectomy or
      hemithyroidectomy was analysed in our patients and compared with the data of the
      literature. Total thyroidectomy (n = 176) did not cause a higher rate of
      complications (hemorrhage: 0.6%, hypocalcemia: 0.6%; recurrent nerve palsy: 0.6%)
      compared to the control group and the literature. Thus, total thyroidectomy can
      offer an efficient therapeutic option in large multinodular goiter.

PMID- 9542029
TI  - [Surgical management of ruptured abdominal aortic aneurysm--diagnosis, risk
      factors and prognosis].
AB  - It has been observed that the number of emergency operations for ruptured
      abdominal aortic aneurysms (AAA) is still high, as is the corresponding
      mortality. With the aim to determine how pre-clinical as well as clinical factors
      affect survival of patients with perforated AAA, we examined the course of
      patients admitted with perforated AAA in the last six years. Retrospectively we
      assessed the following documented parameters: patient's age, pre-clinical
      interval between onset of symptoms and hospitalization, the preoperative
      circulatory situation, hospital resuscitation period before surgery, the duration
      of aortic cross-clamping and the need of intraoperative blood transfusions in
      relation to the hospital mortality. In the period between 1.1.1990-31.12.1995, 39
      patients with ruptured abdominal aortic aneurysms were operated on emergency
      basis in the Department of General Surgery of the University of Essen. There were
      36 men and 3 women. The average age was 69.1 years. 25 patients (64%) died on
      admission, 4 of them intraoperatively. The most relevant observed prognostic
      factors were the preoperative circulatory status (systolic blood pressure p <
      0.0001; hemoglobin p < 0.01) as well as the intraoperative blood transfusion
      requirement (p < 0.01) In view of the high mortality associated with surgical
      treatment of ruptured AAA and with the difficulty to decisively influence the
      relevant prognostic factors, early elective surgery of asymptomatic patients with
      AAA is highly recommended.

PMID- 9542030
TI  - [Risk factors and pathogenic microorganisms in patients with insufficient
      esophagojejunostomy after gastrectomy].
AB  - It was the aim of the study to find by retrospective analysis of data from
      totally gastrectomized patients risk factors for the development of esophago
      jejunal anastomotic leakage, that may be avoidable or influenced therapeutically.
      PATIENTS AND METHODS: The study design was retrospective involving 838 patients
      with total gastrectomy for gastric cancer from the years 1973-1993. In 134 cases
      leakage of the esophago-jejunostomy occurred. The relative risk for the
      development of leakage associated with individual parameters was determined by
      comparing the data from 704 patients without leakage to the data from 134
      patients presenting with this complication. For a subgroup of 86 patients with
      anastomotic leakage microbiological data of swabs taken from the anastomoses were
      available, which were evaluated with respect to potentially pathogenic bacilli.
      RESULTS: The overall leakage rate of esophago-jejunal anastomoses was 15.9% (n =
      134). The mortality rate during this time period amounted to 14.3%. Leakage was a
      most highly significant factor for mortality (p = 0.0001). Significant risk
      factors for leakage of the esophago-jejunostomy were tumors of the cardia,
      splenectomy, a duration of operating time of more than 5 hours and manual suture
      technique compared to stapler anastomoses. Tumor unrelated associated disease,
      tumor stage and a history of other preexisting gastric diseases were not
      associated with an increased relative risk. At the time of the initial clinical
      manifestation of leakage the following pathogenic bacilli could be isolated from
      leaking anastomoses with decreasing incidence: E. coli, S. aureus, Proteus
      mirabilis, Pseudomonas aeruginosa, Klebsiella pneumoniae a.o. The bacterial
      spectrum has not changed during the observation period of 20 years. SUMMARY: With
      the exception of the choice of suture techniques the identified clinical risk
      factors cannot be avoided or influenced therapeutically due to a lack of
      potentially curative treatment alternatives. In contrast potentially pathogenic
      bacilli associated with leakage can be prevented from coming in contact with
      anastomoses thereby preventing infection and leakage.

PMID- 9542032
TI  - [Ethical challenges in preclinical emergency medicine].
AB  - Out-of-hospital emergency medicine, just like any other medical field, must be
      guided by general ethical principles of medical action. These include respecting
      the patient's autonomous decision, acting for his benefit, avoiding harm, and
      justice in distributing the available means. The confrontation with ethical
      conflicts in the routine of emergency medicine is illustrated by a case report.
      The emergency physician, called to a 76-year-old patient with circulatory arrest,
      decides against starting a resuscitation attempt. His decision is based on the
      fact that at least 15 minutes had passed from the cardiac arrest till the arrival
      of the emergency care team, on the previously existing, severe cardiac disease,
      on the age of the patient, on family statements of patient's refusal of
      resuscitation and on the clinical findings of fixed, dilated pupils, missing
      brainstem reflexes, and an asystole as an initially recorded cardiac rhythm. No
      certain clinical signs of death could be observed. In the face of this
      combination of conditions unfavourable for a successful resuscitation attempt and
      a survival of the patient, the emergency physician assumes an obvious futility of
      medical action. The individual criteria are analysed with respect to their
      prognostic value for estimating the chances of surviving out-of-hospital
      circulatory arrest. In the context of resuscitation attempts, the term futility
      can, on the one hand, be defined strictly physiologically, in the sense of the
      clear impossibility of restoring the cardiac pumping function. The extended
      definition of the futility of resuscitation attempts, on the other hand, includes
      an estimate of the nature of survival (duration of survival, neurological
      outcome) after circulatory arrest. The two definitions share the problem of
      containing an evaluation of the objective of out-of-hospital resuscitation
      attempts. In emergency medicine the standard of care remains the start of
      resuscitation attempts. Physiologically defined futility justifies the decision
      to withhold resuscitative efforts. In a particular case the refusal by the
      patient as well as an expected bad prognosis which is inconsistent with the
      patient's interest could support the emergency physician's decision not to
      initiate resuscitation. Such an individual decision should not only be guided by
      medical, but also by ethical considerations and be based on general ethical
      principles.

PMID- 9542031
TI  - [Surgical therapy of non-Hodgkin lymphoma of the stomach].
AB  - The value of surgical treatment is less well defined in gastric lymphoma than in
      gastric carcinoma. Therefore, we analysed the outcome of 245 patients with
      gastric malignancies, which were treated from 1.1.1988 to 31.12.1995 in the
      Department of Surgery/Charite. Twenty patients suffered from a non-Hodgkin
      lymphoma and only 14 (8%) were diagnosed correctly by preoperative endoscopical
      biopsy. Seven patients with limited lymphoma underwent primary surgical therapy
      (total gastrectomy n = 4, subtotal gastrectomy n = 3). Seven patients with
      disseminated lymphoma (stage EIII-IV) were treated by neoadjuvant chemotherapy
      (CHOP), that was followed by gastrectomy (R0: n = 2, R1: n = 4) or explorative
      laparotomy (n = 1). Five patients (25%) were diagnosed as undifferentiated
      carcinoma and underwent total gastrectomy with D2-lymphadenectomy (R0: n = 5).
      One patient (5%) underwent emergency surgery due to gastric perforation. One
      patient (5%) died in hospital due to insufficient anastomosis after total
      gastrectomy and preoperative chemotherapy. Nine patients with high-grade
      malignant lymphomas received postoperative chemotherapy. The 1-, 2,- and 5-year
      survival-rate was 95%, 89% and 44%. Although, many questions are still open,
      surgical therapy remains an important option in the multimodal treatment of
      gastric lymphoma.

PMID- 9542033
TI  - [Anesthesia in laparoscopies: an overview].
AB  - In the last few years laparoscopic surgery requiring a different method of
      anesthesia from laparotomic procedures has been increasingly carried out. Since
      laparoscopic cholecystectomy was first described in 1985 almost all abdominal
      organs can now be operated on laparoscopically. At the same time the spectrum of
      the patients has changed from those who are young and healthy to older ones with
      many accompanying illnesses. In addition, the length of time this operations
      require has greatly increased. Consequently the number of critical incidents
      relevant to anaesthesia, during laparoscopy, has risen. Therefore new studies had
      been worked out which lead to a better understanding of pathophysiological
      changes during pneumoperitoneum.

PMID- 9542035
TI  - [Laparoscopic implantation of catheters for continuous ambulatory peritoneal
      dialysis].
AB  - Continuous ambulatory peritoneal dialysis (CAPD) has become an established
      procedure and is an equal alternative to haemodialysis (HD) in the management of
      terminal renal failure. Nevertheless CAPD still plays a minor role compared with
      HD (10% of all dialyses). CAPD offers advantages in quality of live but is still
      associated with a significant number of complications. The improvement of
      surgical technique and development of new peritoneal dialysis catheters (PDK)
      improved the results of peritoneal dialysis. 3 methods for implantation of PDK
      are used: the open surgical technique, the blind percutaneous procedure and the
      laparoscopic method. The latter technique is currently an accepted practice. 10
      patients were treated by the laparoscopic method. Additionally to the PDK-tunnel
      of the abdominal wall we used 2 trocars (1 x 5 mm, 1 x 12 mm). Advantages of this
      technique are avoiding of perforating lesions, possibility for further operations
      and a safe implantation of the PDK. Peritoneal dialysis was started 7 days after
      operation with initially low dialysate volumes. The observed incidence of
      complications and removed catheters are comparable to the reports in the
      literature.

PMID- 9542034
TI  - [Endoluminal stent prosthesis implantation in thoracic aneurysm of the descending
      aorta--a case report].
AB  - We report on a 72-year old male with a large aneurysm of descending thoracic
      aorta which was treated by implantation of a Dacron-covered self-expanding
      Nitinol stent graft (Talent, HOSMED). The patient was unfit for surgical aneurysm
      resection because of generalised atherosclerosis and cardiomyopathy. We think
      that stent implantation for descending thoracic aortic aneurysms is an attractive
      alternative to surgical aneurysm resection, especially in patients with enhanced
      operative risk. However, further experience, and especially long term-results,
      are required before more widespread application of intra-luminal stent
      implantation in the management of thoracic aortic aneurysms can be recommended.

PMID- 9542036
TI  - [Microcystic adenoma of the pancreas--a case report].
AB  - A 65-year-old female patient with microcystic adenoma of the pancreatic head is
      reported. Under suspicion of a malignant pancreatic tumour a kephalic
      duodenopancreatectomy (Kausch-Whipple) was performed. Diagnosis, therapy,
      prognosis and pathological anatomical aspects of benign microcystic adenoma are
      discussed.

PMID- 9542037
TI  - [As lumbago treated, delayed diagnosis of large intestine perforation with
      extremely severe peritonitis--case report with focus on the value of diagnostic
      laparoscopy].
AB  - We report on a colon perforation with peritonitis which remained clinically
      undetected until the 4th day post trauma although the patient suffered from
      lumbalgia-like symptoms. He then developed an acute abdomen with sudden onset,
      being caused by a sigmoidal rupture and a consecutive diffuse peritonitis. A
      colon resection was performed according to the Hartmann procedure. Almost 36
      revisions were necessary due to necrosis and perforation. Having treated the
      peritonitis successfully it was possible to close the abdomen and to remove the
      stomata. The case is discussed in relation to standard diagnostic procedures
      while a special interest is focused on the usage of sonography, explorative
      laparoscopy and laparotomy. We finally introduce the algorithm being applied to
      similar cases at our trauma center.

PMID- 9542039
TI  - [Relationship between the rate of hepatocyte respiration and body mass in the
      poikilothermic vertebrates].

PMID- 9542038
TI  - [Changes in the composition of the microsomal oxidation system in the cerebral
      cortex of rats during postnatal ontogenesis. Comparison with the retina].

PMID- 9542040
TI  - [O-type sialoglycoproteins from erythrocyte membranes of the lower vertebrates:
      identification and study with the use of lectins].

PMID- 9542041
TI  - [Synthesis of prostaglandins in the isolated fragments of nephrons in various
      vertebrates].

PMID- 9542042
TI  - [Substrate and inhibitor specificity of brain cholinesterase of various fly
      species (Diptera: Anthomyiidae, Muscidae). Enzyme type].

PMID- 9542044
TI  - [Study of mechanisms of the interneuronal interaction based on the reflection
      principal].

PMID- 9542043
TI  - [The role of the left and right hemispheres of the brain in evaluation of the
      point localization in the binocular vision field].

PMID- 9542045
TI  - [Effect of metabotropic glutamate receptors on duration of the post-tetanic
      changes in postsynaptic potentials of motor neurons of the frog Rana ridibunda].

PMID- 9542046
TI  - [Dynamics of changes in temperature of the brain and neck muscles in the
      wakefulness-sleep cycle in hibernating and nonhibernating mammals].

PMID- 9542047
TI  - [Contractile activity of the gastrointestinal system and spontaneous somatomotor
      excitation in the early postnatal ontogenesis of rats].

PMID- 9542048
TI  - [Oxygen deficit after prolonged diving in Baikal seal Pusa sibirica and metabolic
      diving depression].

PMID- 9542049
TI  - [Characteristics of the ultrastructural organization of the arcuate nucleus of
      the rat hypothalamus].

PMID- 9542051
TI  - [Adaptation in invertebrates and comparative pathology of inflammation].

PMID- 9542050
TI  - [Light as the most important factor in evolution: various molecular aspects].

PMID- 9542052
TI  - [Microelectrode study of vestibular neurons in the isolated perfused brain of the
      frog Rana ridibunda].

PMID- 9542053
TI  - [Open oval foramen in the heart of children of different ages].

PMID- 9542054
TI  - [Comparative analysis of substrate specificity of pancreatic serine proteinases
      of different origin].

PMID- 9542055
TI  - [Comparative neurophysiological analysis of the wakefulness-sleep cycle during
      early postnatal ontogenesis in rats and guinea pigs].

PMID- 9542056
TI  - [Corticoid function of the adrenal glands in males of various rat strains
      selected for the reactivity of the reproductive system to the permanent
      illumination].

PMID- 9542057
TI  - [Structural reorganization of the cerebral capillary wall in the Baikal seal Pusa
      sibirica during diving].

PMID- 9542058
TI  - [Structural-functional characteristics of beta- and gamma-subunits of G-proteins
      and molecular mechanisms of their conjugation with other components of the signal
      transduction system].

PMID- 9542059
TI  - [Biological role of carnosine in cell homeostasis].

PMID- 9542060
TI  - An electron spin resonance (ESR) study on the mechanism of ascorbyl radical
      production by metal-binding proteins.
AB  - The mechanism of ascorbate oxidation by metal-binding proteins (ceruloplasmin,
      albumin and transferrin) was investigated in vitro and in isolated plasma by the
      measurement of the ascorbyl free radicals (AFR) by electron spin resonance (ESR).
      In plasma of 13 healthy volunteers, a spontaneous and variable production of AFR
      was detected, which was increased by a 10(-4) M ascorbate overloading; however,
      this increase was not correlated to the intensity of the spontaneous AFR signal.
      The addition of Cu2+ and ceruloplasmin to plasma increased the ESR signal, while
      the addition of transferrin decreased the signal intensity in a dose-dependent
      manner. In vitro, we demonstrated that ascorbate was oxidized by human serum
      albumin and by ceruloplasmin, and that this oxidase-like activity was lost by
      trypsin or heat treatment of these proteins. These two proteins positively
      interacted in the oxidation of ascorbate, since addition of crude albumin to a
      solution of ascorbate and ceruloplasmin increased the intensity of ESR signal in
      a dose-dependent manner. The treatment of albumin by a metal chelator (DDTC)
      abolished these positive interactions. The respective roles of copper and iron in
      ascorbate oxidation were studied and showed a dose-dependent effect of these ions
      on ascorbate oxidation. The role of iron was confirmed by the inhibiting effect
      of metal-free transferrin on iron-dependent ascorbate oxidation. Concerted
      actions between iron carrying albumin and copper carrying ceruloplasmin appear
      responsible for the production of AFR in vitro and in vivo.

PMID- 9542061
TI  - Metal complexes of bovine lactoferrin inhibit in vitro replication of herpes
      simplex virus type 1 and 2.
AB  - The inhibitory effect of bovine lactoferrin (BLf) saturated with ferric,
      manganese or zinc ions, on the infection of Vero cells by human herpes simplex
      virus type 1 (HSV1) and 2 (HSV2) was investigated. Viral infectivity determined
      by intracellular antigen synthesis and plaque formation was efficiently inhibited
      by metal saturated lactoferrins in a dose-dependent manner. Effective BLf
      concentrations which reduced the infection by 50% ranged from 5.2 to 31
      micrograms ml-1 and were far below the cytotoxicity threshold. Fe3+BLf and
      Mn2+BLf exhibited selectivity indexes higher than Zn2+BLf and apoBLf for both
      viruses and the effect was mainly directed towards the early steps of infection.
      The slight viral inhibition shown by the citrate complexes of the different
      metals could indicate that the antiviral effect was not significantly influenced
      by Fe3+, Mn2+ or Zn2+ ions delivered by BLf into the cells.

PMID- 9542062
TI  - Vanadium toxicology--an assessment of general health, haematological aspects and
      energy response in an Indian catfish Clarias batrachus (Linn).
AB  - The pervasive occurrence of vanadium in nature and its use in various industrial
      processes has increased its inputs in the environment. This has prompted us to
      elucidate the impact of vanadium on aquatic environment, the primary body for
      industrial effluent discharge. The energy response of the fish, Clarias
      batrachus, its haematological status including haemoglobin (Hb), haematocrit
      (Ht), leutocrit (Lt), mean corpuscular haemoglobin (MCH), mean corpuscular volume
      (MCV), mean corpuscular haemoglobin concentration (MCHC) etc. And overall general
      health conditions have been observed to be significantly hampered leading to
      deleterious alterations in the general metabolism of the fish following long term
      exposure to vanadate. The increase in muscle and tissue lactic acid (2-12 fold)
      in association with decrease in pyruvic acid (72% in muscle; 26% in liver)
      reflect a shift towards an anaerobic metabolism of the fish. We conclude that
      vanadium could be toxic for the fish in question under long term exposure at the
      doses under observation (2-10 mg L-1).

PMID- 9542063
TI  - Evidence for the involvement of vacuolar activity in metal(loid) tolerance:
      vacuolar-lacking and -defective mutants of Saccharomyces cerevisiae display
      higher sensitivity to chromate, tellurite and selenite.
AB  - The responses of Saccharomyces cerevisiae towards the oxyanions tellurite,
      selenite and chromate were investigated in order to establish the involvement of
      the yeast vacuole in their detoxification. Three mutants of S. cerevisiae with
      defective vacuolar morphology and function were used; mutant JSR180 delta 1 is
      devoid of any vacuolar-like structure while ScVatB and ScVatC are deficient in
      specific protein subunits of the vacuolar (V)-H(+)-ATPase. All the mutant strains
      showed increased sensitivity to tellurite and chromate compared to their parental
      strains. Such sensitivity of the mutants was associated with increased
      accumulation of tellurium and chromium. These results indicate that accumulation
      of both tellurium and chromium occurred mainly in the cytosolic compartment of
      the cell, with detoxification influenced by the presence of a functionally-active
      vacuole which may play a role in compartmentation as well as regulation of the
      cytosolic compartment for optimal expression of a detoxification mechanism, e.g.
      reduction. In contrast, the vacuolar-lacking mutant, JSR180 delta 1, and the
      defective V-H+ATPase mutant ScVatB displayed lower selenium accumulation than
      their parental strains. Additionally, the mutant strain ScVatB displayed a higher
      tolerance to selenite than the parental strain. This result suggests that
      accumulation of selenium occurs mainly in the vacuolar compartment of the cell
      with tolerance depending on the ability of the cytosolic component to reduce
      selenite to elemental selenium, which might, in turn, be related to activity of
      the V-H(+)-ATPase. These results are discussed in relation to vacuolar
      compartmentation and the significance of the vacuolar H(+)-ATPase in cytosolic
      homeostasis of H+ both of which may affect the accumulation, reduction, and
      tolerance to the tested metal(loids).

PMID- 9542064
TI  - Morphology and proliferation of B16 melanoma cells in the presence of lanthanoid
      and Al3+ ions.
AB  - The effects of trivalent metal ions such as lanthanoid (La3+, Ce3+, Nd3+, Sm3+,
      Gd3+, Er3+, Yb3+, Lu3+) and Al3+ ions on the morphological change and
      proliferation of B16 melanoma cells in culture are discussed. These metal ions
      induced morphological transformations and decreased growth rates at doses of 1
      mM. B16 melanoma cells treated with La3+, Ce3+, Nd3+, Sm3+, and Gd3+ showed
      polyhedrical spreading. Elongation of axones was dependent on the metal ions. B16
      melanoma cells treated with Er3+, Yb3+, Lu3+, and Al3+ showed a long slender
      shape. Growth rates of melanoma cells in the presence of 1 mM of metal ions
      (La3+, Ce3+, Nd3+, Sm3+, Gd3+, Yb3+, Al3+) were significantly lower than that of
      control cells. Measurements of cell cycle indicated that the metal ions arrested
      the transitions from G0/G1 to S state.

PMID- 9542065
TI  - Haemodynamic effects of macrocyclic and linear gadolinium chelates in rats: role
      of calcium and transmetallation.
AB  - Several studies were undertaken to compare four magnetic resonance imaging (MRI)
      contrast media (CM) as regards acute haemodynamic effects in rats and to
      investigate the mechanisms involved. (1) Normotensive rats received a rapid bolus
      intravenous injection of 0.5 mmol kg-1 of each CM. The effects of Gd-DOTA, Gd-HP
      DO3A, Gd-DTPA and Gd-DTPA-BMA on blood pressure (BP) were compared. (2) The
      haemodynamic effects of Gd-DTPA (0.5 mmol kg-1) were compared to those of
      isovolumic and isoosmolar Zn-DTPA and glucose solutions. (3) The haemodynamic
      profiles of Gd-DTPA and Gd-DTPA-BMA were recorded with and without addition of
      ionized calcium. (4) The mechanism of Gd-HP-DO3A-induced transient rise in BP was
      investigated by evaluating the effects of phentolamine or diltiazem pretreatment.
      For (1) the greatest drop in BP occurred following Gd-DTPA (a linear chelate)
      injection (-18 +/- 2% vs baseline, P < 0.01). Gd-DTPA-BMA, another lineate
      chelate, also induced a slight but significant reduction in BP (-8 +/- 2% at 45
      s, P < 0.05). Gd-DOTA, a macrocyclic CM, had virtually no haemodynamic effects.
      For (2) the Gd-DTPA-induced drop in BP was greater than that of the osmolality
      matched glucose control and lower than that of osmolality-matched Zn-DTPA. For
      (3) a transmetallation phenomenon versus free ionized calcium is possible in the
      case of both linear CM (Gd-DTPA and Gd-DTPA-BMA) since Ca2+ significantly reduced
      the CM-induced decrease in BP. For (4) a transient rise in BP was observed
      following Gd-HP-DO3A, another macrocyclic chelate, associated with a concomitant
      increase in stroke volume. This effect was antagonized neither by phentolamine
      nor by diltiazem. The decrease in BP following injection of Gd-DTPA or Gd-DTPA
      BMA may not only be osmolality-related since (a) Gd-DOTA solution, whose
      osmolality is greater than that of Gd-DTPA-BMA, had a lesser effect, and (b) this
      hypotensive effect was corrected by a addition of ionized calcium. The transient
      Gd-HP-DO3A-induced rise in BP is probably the consequence of a positive inotropic
      effect.

PMID- 9542066
TI  - Molecular recognition of siderophores: a study with cloned ferrioxamine receptors
      (FoxA) from Erwinia herbicola and Yersinia enterocolitica.
AB  - The outer membrane receptor for ferrioxamines (FoxAErw) of Erwinia herbicola
      (Pantoea agglomerans) was cloned from a cosmid gene bank and partially sequenced.
      A comparison of the partial amino acid sequence of FoxAErw with the amino acid
      sequence of FoxAYer from Yersinia enterocolitica revealed a high sequence
      homology. A functional analysis of FoxAErw and FoxAYer receptors cloned into a
      Fhu-negative background (HK97) revealed that ferrioxamines are recognized at very
      low concentrations (< 10 pmoles) in growth promotion bioassays. A collection of
      ferrioxamine derivatives containing varying chain lengths and ether bridges
      within the molecule was also accepted. However, the three ether containing
      ferrioxamine (Et3) behaved differently in the two FoxA receptors. Coprogen was
      also recognized to a certain extent, whereas ferrichromes were completely
      excluded from the FoxA receptors, confirming that coprogens share some structural
      similarities with the ferrioxamines. FoxA mutants (FM13) of Erwinia herbicola
      obtained by ferrimycin selection showed no uptake of 55Fe-labelled ferrioxamine E
      and B any more, while the transport of coprogen and ferrichrome was unaffected or
      even slightly increased.

PMID- 9542067
TI  - Recovery of gold from thiourea solutions using microorganisms.
AB  - The recovery of gold from gold-thiourea solutions using various types of waste
      biomass was investigated. All organisms tested, namely, Saccharomyces cerevisiae,
      Spirulina platensis and Streptomyces erythraeus removed gold rapidly from gold
      thiourea solutions. The process of gold accumulation was pH-dependent for
      Saccharomyces ceresvisiae and Streptomyces erythraeus and independent of pH in
      the case of Spirulina platensis. Of all strains of microorganisms examined,
      Spirulina platensis had the highest affinity and capacity for gold even at low pH
      values. Thus, all three microorganisms tested for their ability to recover gold
      from gold-thiourea solutions can therefore be used in biotechnological
      applications, especially Spirulina platensis which has the highest binding
      capacity for gold at low pH values.

PMID- 9542068
TI  - Lipid peroxidative damage on cadmium exposure and alterations in antioxidant
      system in rat erythrocytes: a study with relation to time.
AB  - Cadmium induced lipid peroxidation (LPO) and the activity of antioxidant enzymes
      after the administration of a single dose of CdCl2 (0.4 mg kg-1 body wt, i.p.)
      was studied in rat erythrocytes. Cd intoxication increased erythrocyte LPO along
      with a decrease in superoxide dismutase (SOD) up to three days of Cd treatment.
      The decrease in erythrocyte catalase (CAT) activity was marked within 9 h of Cd
      intoxication. After three days of Cd treatment, LPO decreased towards normal,
      along with an increase in erythrocyte SOC and CAT activity. Blood glutathione
      (GSH) decreased significantly within 24 h of Cd treatment, followed by an
      increase towards normal. Erythrocyte glutathione S-transferase (GST) activity
      increased up to 10 days of Cd intoxication, probably in an attempt to reduce Cd
      toxicity. Serum glutamate pyruvate transaminase (SGPT), serum alkaline
      phosphatase (SALP) and serum bilirubin increased up to 10 days of Cd
      intoxication. Blood urea increased significantly up to three days, followed by a
      decrease towards normal. The results show that Cd induced LPO was associated with
      a decrease in antioxidant enzymes and GSH in erythrocytes; as these antioxidants
      increase in erythrocytes with recovery from Cd intoxication, the Cd induced LPO
      reversed towards normal. The increase in the SGPT, SALP and serum bilirubin
      correlated with LPO. The results suggest that Cd intoxication induces oxidative
      stress and alters the antioxidant system, resulting in oxidative damage to rat
      erythrocytes.

PMID- 9542069
TI  - An analysis of structural similarity in the iron and manganese superoxide
      dismutases based on known structures and sequences.
AB  - There are two types of homologous enzymes catalysing the dismutation of the
      superoxide radical--Cu-Zn superoxide dismutases, and manganese or iron superoxide
      dismutases. In the latter two forms there is a high percentage of identity in the
      primary structures, and the tertiary structures are very similar particularly in
      the areas of the active site and in the residues responsible for the formation of
      the dimer. The quaternary structure of the dimer is also highly conserved.
      However, it has been found that despite this conservation there is strong metal
      ion specificity and many enzymes in the family will only be active if the correct
      metal ion is present. The purpose of this study has been to analyse solved X-ray
      structures for interactions common in both the manganese and iron forms and those
      that are specific to each, which may indicate reasons for the metal ion
      specificity. Initial analysis points to the probability that it is a combination
      of a number of residues, and not necessarily the same ones in every instance,
      which confer the specificity. In addition we have identified some anomalies in
      the currently available Fe/MnSOD structures which may require further remodelling
      and refinement.

PMID- 9542070
TI  - Revised group classification of the genus Spiroplasma.
AB  - Significant changes have been made in the systematics of the genus Spiroplasma
      (class Mollicutes) since it was expanded by revision in 1987 to include 23 groups
      and eight sub-groups. Since that time, two additional spiroplasmas have been
      assigned group numbers and species names. More recently, specific epithets have
      been assigned to nine previously designated groups and three sub-groups. Also,
      taxonomic descriptions and species names have been published for six previously
      ungrouped spiroplasmas. These six new organisms are: Spiroplasma alleghenense
      (strain PLHS-1T) (group XXVI), Spiroplasma lineolae (strain TALS-2T) (group
      XXVII), Spiroplasma platyhelix (strain PALS-1T) (group XXVIII), Spiroplasma
      montanense (strain HYOS-1T) (group XXXI), Spiroplasma helicoides (strain TABS-2T)
      (group XXXII) and Spiroplasma tabanidicola (strain TAUS-1T) (group XXXIII). Also,
      group XVII, which became vacant when strain DF-1T (Spiroplasma chrysopicola) was
      transferred to group VIII, has been filled with strain Tab 4c. The discovery of
      these strains reflects continuing primary search in insect reservoirs,
      particularly horse flies and deer files (Diptera: Tabanidae). In the current
      revision, new group designations for 10 spiroplasma strains, including six
      recently named organisms, are proposed. Three unnamed but newly grouped
      spiroplasmas are strain TIUS-1 (group XXIX; ATCC 51751) from a typhiid wasp
      (Hymenoptera: Tiphiidae), strain BIUS-1 (group XXX; ATCC 51750) from floral
      surfaces of the tickseed sunflower (Bidens sp.) and strain BARC 1901 (group
      XXXIV; ATCC 700283). Strain BARC 2649 (ATCC 700284) from Tabanus lineola has been
      proposed as a new sub-group of group VIII. Strains TIUS-1 and BIUS-1 have unusual
      morphologies, appearing as helices at only certain stages in culture. In this
      revision, potentially important intergroup serological relationships observed
      between strain DW-1 (group II) from a neotropical Drosophila species and certain
      sub-group representatives of group I spiroplasmas are also reported.

PMID- 9542071
TI  - Rhizobium mongolense sp. nov. is one of three rhizobial genotypes identified
      which nodulate and form nitrogen-fixing symbioses with Medicago ruthenica [(L.)
      Ledebour].
AB  - Medicago ruthenica [(L.) Ledebour] is native to inner Mongolia where rhizosphere
      samples were collected for the isolation of 106 rhizobial cultures. Besides
      nodulating the original trap host, the isolates formed nitrogen-fixing symbioses
      with Phaseolus vulgaris. Only half of the isolates nodulated alfalfa (Medicago
      sativa), but these did not form nitrogen-fixing symbioses. Rhizobium tropici also
      formed nitrogen-fixing symbioses with Medicago ruthenica. A total of 56
      distinctive multilocus electrophoretic types (ETs) were identified among 94 of
      the 106 isolates which were analysed for variation in electrophoretic mobility of
      12 enzyme loci. One isolate (USDA 1920) possessed a unique ET, while the ETs of
      the other isolates formed two weakly divergent subgroups approximately equal in
      size. It was concluded from small subunit rRNA gene sequences of eight isolates
      of Medicago ruthenica that they belonged to the genus Rhizobium and not to the
      genus Sinorhizobium which is more commonly associated with Medicago. Genomic
      similarity, determined from DNA hybridization analysis, between USDA 1920 and the
      strain representing the remaining isolates (USDA 1844) was lower than 20%. Based
      upon these observations it was concluded that at least three genomic species of
      rhizobia form nitrogen-fixing symbioses with Medicago ruthenica. One of these
      genomic species is R. tropici, another is represented by the single isolate USDA
      1920 and the name Rhizobium mongolense is proposed for the third genomic species
      represented by USDA 1844.

PMID- 9542072
TI  - Thermococcus gorgonarius sp. nov. and Thermococcus pacificus sp. nov.:
      heterotrophic extremely thermophilic archaea from New Zealand submarine hot
      vents.
AB  - Two extremely thermophilic archaea, designated W-12 and P-4, were isolated from a
      geothermal vent in the tidal zone of Whale Island, New Zealand, and from
      geothermally heated bottom deposits of the Bay of Plenty, New Zealand,
      respectively. Cells of isolate W-12 are irregular cocci, 0.3-1.2 microns in
      diameter, motile with polar flagella. The cell envelope consists of one layer of
      subunits with a major protein of M(r) 75,000. Cells produce protrusions of
      different kinds: prostheca-like, chains of bubbles, or network of fimbriae. Cells
      of isolate P-4 are regular cocci, 0.7-1.0 micron in diameter, motile with polar
      flagella. The cell envelope consists of two layers of subunits; its major protein
      has an M(r) of 56,000. Both organisms are obligate anaerobes, fermenting peptides
      in the case of strain W-12, or peptides and starch in the case of P-4. Elemental
      sulfur is required for growth and is reduced to hydrogen sulfide. The optimal
      growth temperature of the new isolates is in the range 80-88 degrees C. The
      optimal growth pH is 6.5-7.2. The G + C content of the DNA of strain W-12 is 50.6
      mol%, and of strain P-4 is 53.3 mol%. Based on physiological characteristics, 165
      rDNA sequence comparison and DNA base composition, the new isolates were
      considered to be members of the genus Thermococcus. The low level of DNA-DNA
      hybridization with the type strains of other Thermococcus species confirms the
      novel species status of the new isolates. The new isolates are described as
      Thermococcus gorgonarius sp. nov., with type strain W-12 (= DSM 10395T), and
      Thermococcus pacificus sp. nov., with type strain P-4 (= DSM 10394T).

PMID- 9542074
TI  - Biochemical and genetic characterization of a Prevotella intermedia/nigrescens
      like organism.
AB  - Thirty-three previously non-typable faintly pigmented Gram-negative anaerobic
      bacterial isolates, biochemically most closely related to Prevotella intermedia
      and Prevotella nigrescens, were analysed for enzymic reactions, cellular fatty
      acid (CFA) composition, electrophoretic mobility of malate and glutamate
      dehydrogenases, hybridization with P. intermedia and P. nigrescens species
      specific oligonucleotide probes and, for genetic heterogeneity, by arbitrarily
      primed PCR (AP-PCR). P. intermedia ATCC 25611T and P. nigrescens ATCC 33563T were
      run in parallel for comparison. Twenty-nine isolates originated from the normal
      oral flora of 18 subjects (including five mother-child pairs), and four isolates
      from various infections. Except for a negative lipase reaction, enzymic profiles
      of the test isolates were similar to those of P. intermedia and P. nigrescens.
      Clustering of CFAs, electrophoretic mobility patterns, hybridization with DNA
      probes for P. intermedia and P. nigrescens, and AP-PCR band patterns of the test
      isolates differed from those of the type strains of P. intermedia and P.
      nigrescens, suggesting the existence, in humans, of a new anaerobic species of
      pigmented, moderately saccharolytic, indole-positive Gram-negative rods.

PMID- 9542073
TI  - Sulfur-inhibited Thermosphaera aggregans sp. nov., a new genus of
      hyperthermophilic archaea isolated after its prediction from environmentally
      derived 16S rRNA sequences.
AB  - Recently, a new procedure was developed which allowed for the first time the
      isolation of a hyperthermophilic archaeum tracked by 165 rRNA analysis from a
      terrestrial hot solfataric spring ('Obsidian Pool', Yellowstone National Park,
      WY, USA). This novel isolate is characterized here. Cells are round cocci with a
      diameter of 0.2-0.8 micron, occurring singly, in pairs, short chains and in grape
      like aggregates. The aggregates exhibit a weak bluish-green fluorescence under UV
      radiation at 420 nm. The new isolate is an anaerobic obligate heterotroph, using
      preferentially yeast extract for growth. The metabolic products include CO2, H2,
      acetate and isovalerate. Growth is observed between 65 and 90 degrees C (optimum:
      85 degrees C), from pH 5.0 to 7.0 (optimum: 6.5) and up to 0.7% NaCl. The
      apparent activation energy for growth is about 149 kJ mol-1. Elemental sulfur or
      hydrogen inhibits growth. The core lipids consist mainly of acyclic and cyclic
      glycerol diphytanyl tetraethers. The cell envelope contains a cytoplasmic
      membrane covered by an amorphous layer of unknown composition; there is no
      evidence for a regularly arrayed surface-layer protein. The G + C content is 46
      mol%. On the basis of 165 rRNA sequence comparisons in combination with
      morphological, physiological and biochemical properties, the isolate represents a
      new genus within the Desulfurococcaceae, which has been named Thermosphaera. The
      type species is Thermosphaera aggregans, the type strain is isolate M11TLT (= DSM
      11486T).

PMID- 9542076
TI  - Saccharopolyspora spinosporotrichia sp. nov., a novel actinomycete from soil.
AB  - The generic position of an aerobic, Gram-positive, non-acid-alcohol-fast
      actinomycete was determined following isolation of the PCR-amplified 16S rRNA
      genes and alignment of the resultant sequence with corresponding sequences from
      representatives of the family Pseudonocardiaceae. The assignment of the organism
      to the genus Saccharopolyspora was strongly supported by chemotaxonomic and
      morphological data. The strain was distinguished from representatives of validly
      described Saccharopolyspora species by a number of phenotypic properties. It is
      proposed that the organism, strain AS4.198T, be classified in the genus
      Saccharopolyspora as Saccharopolyspora spinosporotrichia sp. nov.

PMID- 9542075
TI  - Phylogenetic characterization and proposal of a new pigmented species to the
      genus Prevotella: Prevotella pallens sp. nov.
AB  - Complete 16S rRNA gene sequences of three representative strains of anaerobic,
      Gram-negative, pigmented, moderately saccharolytic, indole-positive bacteria
      isolated from the oral cavity of humans were determined. According to comparative
      analyses of the rRNA sequence data, this organism represents a previously unknown
      species within the genus Prevotella. In addition, 22 representative strains and
      21 reference strains (including 11 Prevotella intermedia and 10 Prevotella
      nigrescens strains) were subjected to multilocus enzyme electrophoretic analysis.
      The strains were consistently separated into three clearly distinct groups,
      corresponding to their previous entities. On the basis of the present
      phylogenetic results that confirmed our biochemical and genetic data, we propose
      a new species, Prevotella pallens. The type strain is NCTC 13042 (= AHN 10371).

PMID- 9542077
TI  - Streptomyces thermocarboxydovorans sp. nov. and Streptomyces thermocarboxydus sp.
      nov., two moderately thermophilic carboxydotrophic species from soil.
AB  - Four moderately thermophilic, carboxydotrophic streptomycetes were the subject of
      a comparative taxonomic investigation designed to establish their taxonomic
      relationships. Almost complete sequences of the 16S rRNA genes of the test
      strains were determined following the isolation and direct sequencing of the
      amplified genes. The resultant nucleotide sequences were aligned with the
      sequences of previously studied streptomycetes, and phylogenetic trees generated
      by using the neighbour-joining, Fitch-Margoliash, maximum-likelihood and maximum
      parsimony methods. It was evident from the phylogenetic analyses that strains
      AT50, AT51 and AT52 were most closely related to Streptomyces thermodiastaticus
      DSM 40573T and strain AT37 to Streptomyces glaucescens DSM 40716 and Streptomyces
      pseudogriseolus NRRL 3985. Random DNA amplification profiles clearly
      distinguished strains AT50, AT51 and AT52 from Streptomyces thermodiastaticus and
      from strain AT37. The molecular systematic evidence, together with phenotypic
      data derived from this and previous studies, indicate that the test strains merit
      species status within the genus Streptomyces. The name Streptomyces
      thermocarboxydovorans sp. nov. is proposed for strains AT50, AT51 and AT52 (type
      strain) and Streptomyces thermocarboxydus sp. nov. for strain AT37.

PMID- 9542078
TI  - Description of some coryneform bacteria isolated from human clinical specimens as
      Corynebacterium falsenii sp. nov.
AB  - Over a five-year period, four strains of a yellowish-pigmented coryneform
      bacterium were received for identification by the Culture Collection of the
      University of Goteborg. All strains had been isolated from normally sterile human
      body fluids. Initial biochemical characterization revealed that all four isolates
      were very similar, with weak pyrazinamidase and urease activities, as well as
      slow fermentative acid production from glucose as the most significant phenotypic
      features which differentiated the strains from all other presently defined
      corynebacteria. Chemotaxonomic investigations demonstrated that the strains
      belonged to the genus Corynebacterium. SDS-PAGE of whole-cell proteins suggested
      that all four strains were representatives of the same species. Comparative 16S
      rRNA gene sequence analysis unambiguously demonstrated that the four strains were
      genealogically related and represent a new subline within the genus
      Corynebacterium for which the designation Corynebacterium falsenii sp. nov. is
      proposed. The type strain of Corynebacterium falsenii is CCUG 33651.

PMID- 9542079
TI  - Phylogeny of the family Moraxellaceae by 16S rDNA sequence analysis, with special
      emphasis on differentiation of Moraxella species.
AB  - Thirty-three strains previously classified into 11 species in the bacterial
      family Moraxellaceae were subjected to phylogenetic analysis based on 16S rRNA
      sequences. The family Moraxellaceae formed a distinct clade consisting of four
      phylogenetic groups as judged from branch lengths, bootstrap values and signature
      nucleotides. Group I contained the classical moraxellae and strains of the coccal
      moraxellae, previously known as Branhamella, with 16S rRNA similarity of > or =
      95%. A further division of group I into five tentative clusters is discussed.
      Group II consisted of two strains representing Moraxella atlantae and Moraxella
      osloensis. These strains were only distantly related to each other (93.4%) and
      also to the other members of the Moraxellaceae (< or = 93%). Therefore, reasons
      for reclassification of these species into separate and new genera are discussed.
      Group III harboured strains of the genus Psychrobacter and strain 752/52 of
      [Moraxella] phenylpyruvica. This strain of [M.] phenylpyruvica formed an early
      branch from the group III line of descent. Interestingly, a distant relationship
      was found between Psychrobacter phenylpyruvicus strain ATCC 23333T (formerly
      classified as [M.] phenylpyruvica) and [M.] phenylpyruvica strain 752/52,
      exhibiting less than 96% nucleotide similarity between their 16S rRNA sequences.
      The establishment of a new genus for [M.] phenylpyruvica strain 752/52 is
      therefore suggested. Group IV contained only two strains of the genus
      Acinetobacter. Strategies for the development of diagnostic probes and
      distinctive sequences for 16S rRNA-based species-specific assays within group I
      are suggested. Although these findings add to the classificatory placements
      within the Moraxellaceae, analysis of a more comprehensive selection of strains
      is still needed to obtain a complete classification system within this family.

PMID- 9542080
TI  - Caldicellulosiruptor owensensis sp. nov., an anaerobic, extremely thermophilic,
      xylanolytic bacterium.
AB  - An anaerobic, extremely thermophilic, xylanolytic, non-spore-forming bacterium
      was isolated from a sediment sample taken from Owens Lake, California, and
      designated strain OLT (T = type strain). Strain OLT had a Gramnegative reaction
      and occurred as short rods which sometimes formed long chains containing a few
      coccoid cells. It grew at 50-80 degrees C, with an optimum at 75 degrees C. The
      pH range for growth was 5.5-9.0 with an optimum at about pH 7.5. When grown on
      glucose at optimal conditions, its doubling time was 7.3 h. In addition to
      glucose, the isolate utilized sucrose, xylose, fructose, ribose, xylan, starch,
      pectin and cellulose. Yeast extract stimulated growth on carbohydrates but was
      not obligately required. The end products from glucose fermentation were lactate,
      acetate, ethanol, H2 and CO2. The G + C content of strain OLT was 36.6 mol%. The
      16S rDNA sequence analysis indicated that strain OLT was a member of the
      subdivision containing Gram-positive bacteria with DNA G + C content of less than
      55 mol% and clustered with members of the genus Caldicellulosiruptor. Because
      strain OLT is phylogenetically and phenotypically different from other members of
      this genus, it is proposed to designate this isolate Caldicellulosiruptor
      owensensis sp. nov. Strain OLT is the type strain (= ATCC 700167T).

PMID- 9542081
TI  - PCR fingerprinting of whole genomes: the spacers between the 16S and 23S rRNA
      genes and of intergenic tRNA gene regions reveal a different intraspecific
      genomic variability of Bacillus cereus and Bacillus licheniformis [corrected].
AB  - Genomic diversity in 21 strains of Bacillus cereus and 10 strains of Bacillus
      licheniformis was investigated by random amplified polymorphic DNA (RAPD)
      analysis, which samples the whole genome, and by two PCR fingerprinting
      techniques sampling the hypervariable spacers between the conserved 16S and 23S
      rRNA genes of the rRNA gene operon (ITS-PCR) and regions between tRNA genes (tDNA
      PCR). RAPD analysis showed a remarkable diversity among strains of B. cereus that
      was not observed with the rRNA and tRNA intergenic-spacer-targeted PCR, where all
      the strains showed practically identical fingerprints. A wide variability among
      the B. cereus strains was also observed in the plasmid profiles, suggesting that
      the genetic diversity within B. cereus species can arise from plasmid transfer.
      One contribution to the diversity detected by RAPD analysis was determined by the
      presence of large extrachromosomal elements that were amplified during RAPD
      analysis as shown by Southern hybridization experiments. In contrast to the
      strains of B. cereus, the 10 strains of B. licheniformis were grouped into two
      clusters which were the same with all the methods employed. The 16S rRNA genes
      were identical in all 10 strains when examined using single strand conformation
      polymorphism analysis after digestion with Alul and Rsal. From these data we
      hypothesize two different evolutionary schemes for the two species.

PMID- 9542082
TI  - Whole-cell protein electrophoretic analysis of viridans streptococci: evidence
      for heterogeneity among Streptococcus mitis biovars.
AB  - One hundred reference strains representing all species belonging to the different
      phylogenetic lineages of the viridans streptococci were examined by means of one
      dimensional whole-organism protein electrophoresis. For most of the species
      examined, multiple strains characterized by DNA-DNA hybridization were included
      and, wherever described, representatives of different biochemical variants were
      analysed. Most species were clearly differentiated. The data support the
      viewpoint that members of the Streptococcus anginosus group constitute a single
      species and indicate that Streptococcus mitis biovar 2 is a heterogeneous taxon
      comprising strains from several streptococcal species.

PMID- 9542083
TI  - Comparison of PCR-based DNA fingerprinting techniques for the identification of
      Listeria species and their use for atypical Listeria isolates.
AB  - Four PCR-based DNA fingerprinting techniques were compared for their ability to
      identify at the species level a heterogeneous collection of isolates belonging to
      the six valid Listeria species. 16S rDNA-RFLP analysis identified all species and
      16S rDNA-SSCP analysis identified almost all species. Also, isolates with unusual
      biochemical characteristics and/or unusual antigenic composition could be
      identified correctly. rRNA-intracistronic length polymorphism analysis suffered
      from high intraspecific variability, a limited number of fragments per profile,
      and small length differences between the spacers of different species. tRNA
      intergenic length polymorphism analysis resulted in identification of all
      isolates but one, when fluorescent DNA capillary electrophoresis was used such
      that fragment length differences of 1 bp could be resolved. The four techniques
      yielded comparable results relevant to the taxonomy of Listeria. They all
      indicate a high degree of genetic relatedness between L. innocua and L.
      welshimeri, homogeneity of L. grayi, distinct but clear relatedness of L. grayi
      to the other Listeria species, a clear distinction between the two subspecies of
      L. ivanovii, and a clear distinction between Listeria isolates and isolates from
      closely related taxa or from species which are phenotypically difficult to
      distinguish from Listeria. New sequence determination of the 16S rRNA gene was
      necessary to obtain sequences in accordance with the findings of 16S rDNA-RFLP
      analysis.

PMID- 9542084
TI  - Two new Rahnella genomospecies that cannot be phenotypically differentiated from
      Rahnella aquatilis.
AB  - Fifty-one Rahnella aquatilis and R. aquatilis-like strains from water, snails and
      human sources were characterized by routine biochemical tests, carbon source
      utilization tests, DNA relatedness (hydroxyapatite method) and 16S rRNA
      sequencing. The results of the genetic methods indicated that the strains
      comprised three closely related species within the genus Rahnella. It was not
      possible to differentiate R. aquatilis from the two newly recognized species. The
      new species were therefore given the vernacular names Rahnella genomospecies 2
      and Rahnella genomospecies 3.

PMID- 9542086
TI  - Classification of heparinolytic bacteria into a new genus, Pedobacter, comprising
      four species: Pedobacter heparinus comb. nov., Pedobacter piscium comb. nov.,
      Pedobacter africanus sp. nov. and Pedobacter saltans sp. nov. proposal of the
      family Sphingobacteriaceae fam. nov.
AB  - Sixteen heparinase-producing isolates, related to Sphingobacterium heparinum,
      were grouped into three major clusters by SDS-PAGE and DNA-rRNA hybridizations.
      Based on a polyphasic approach, it was shown that isolates of two of these
      clusters and S. heparinum species belong to a new genus for which the name
      Pedobacter is proposed. The genus consists of Pedobacter heparinus comb. nov.
      (formerly Sphingobacterium heparinum), which is the type species, Pedobacter
      piscium comb. nov. (formerly Sphingobacterium piscium), Pedobacter africanus sp.
      nov. and Pedobacter saltans sp. nov. and four as-yet-unnamed DNA hybridization
      groups. All the previously named taxa can be discriminated by phenotypic
      features, but have strong overall similarities with representatives of the genus
      Sphingobacterium and the misclassified species [Flexibacter] canadensis. All
      these organisms constitute a separate rRNA branch in rRNA superfamily V for which
      the family Sphingobacteriaceae fam. nov. is proposed.

PMID- 9542085
TI  - New aerobic ammonium-dependent obligately oxalotrophic bacteria: description of
      Ammoniphilus oxalaticus gen. nov., sp. nov. and Ammoniphilus oxalivorans gen.
      nov., sp. nov.
AB  - The genus Ammoniphilus is proposed for aerobic endospore-forming Gram-variable
      rod-shaped bacteria, which are ammonium-dependent, obligately oxalotrophic and
      haloalkalitolerant, oxidase- and catalase-positive, mesophilic and motile by
      peritrichous flagella. Cell wall contained two electron-dense layers. The
      external layer consists of a chain of electron-dense granules morphologically
      resembling the cellulosomes of Clostridium thermocellum. Two species are
      described, Ammoniphilus oxalaticus gen. nov., sp. nov. and Ammoniphilus
      oxalivorans gen. nov., sp. nov. The type strains of these species are strains
      RAOx-1 (= DSM 11538) and RAOx-FS (= DSM 11537), respectively. Ammoniphilus
      strains were isolated from the rhizosphere of sorrel (Rumex acetosa) and from
      decaying wood. The strains require a high concentration of ammonium ions and use
      oxalate as the sole organic source of carbon and energy for growth; no growth
      factors were required. Growth occurred at pH 6.8-9.5. The optimum temperature and
      pH for growth were 28-30 degrees C and 8.0-8.5. All strains grew in a saturated
      solution of ammonium oxalate, and tolerated 3% NaCl. Whole-cell hydrolysates
      contain meso-diaminopimelic acid and glucose. The menaquinone of the strains was
      MK 7, and the major cellular fatty acids were 12-methyl tetradecanoic, cis
      hexadec-9-enoic and hexadecanoic acids. The G + C content of the DNA was 45-46
      mol% for A. oxalaticus and 42 mol% for A. oxalivorans. The almost complete 16S
      rDNA sequence of three strains of the two species of Ammoniphilus shows that the
      genus falls into the radiation of the Clostridium-Bacillus subphylum of Gram
      positive bacteria. The closest phylogenetic neighbour of Ammoniphilus is
      Oxalophagus oxalicus. The DNA-DNA hybridization value between strains RAOx-1 and
      RAOx-FS was 39.7%.

PMID- 9542087
TI  - Reclassification of Shewanella putrefaciens Owen's genomic group II as Shewanella
      baltica sp. nov.
AB  - The taxonomic relationship between several Shewanella putrefaciens isolates from
      the Baltic Sea and reference strains of this species is presented in this study.
      Results from DNA-DNA hybridization using a newly developed non-radioactive
      detection system and from 16S rRNA gene sequencing demonstrated that S.
      putrefaciens is a heterogeneous species containing more than a single genomic
      group. The genomic group II was phylogenetically, genotypically and
      phenotypically distant enough from the species type strain to be classified as a
      single species within the genus Shewanella. Therefore, we propose to reclassify
      Owen's genomic group II as Shewanella baltica sp. nov. with the type strain NCTC
      10735.

PMID- 9542088
TI  - Inter- and intraspecific phylogenetic analysis of the genus Nocardioides and
      related taxa based on 16S rDNA sequences.
AB  - The 16S rDNAs from 38 strains of the genus Nocardioides, two Aeromicrobium
      species and Terrabacter tumescens were directly sequenced and then analysed. The
      mean nucleotide similarity value between the type strains of validly described
      Nocardioides species was 96.1 +/- 3.0%. The mean nucleotide similarity value
      between the type strains of validly described Nocardioides species and the two
      Aeromicrobium species was 93.7 +/- 1.4% T. tumescens was distantly related to the
      genera Nocardioides and Aeromicrobium. The mean intraspecific nucleotide
      similarity value of 16S rDNA sequences from Nocardioides albus was 99.5 +/- 0.5%.
      The mean intraspecific nucleotide similarity of 16S rDNA sequences from
      Nocardioides simplex was 100%, except for N. simplex strains ATCC 13260, ATCC
      19565 and ATCC 19566, which were shown not to be members of the genus
      Nocardioides. 'Nocardioides flavus' strains IFO 14396T and IFO 14397, and
      'Nocardioides fulvus' JCM 3335T showed a 16S rDNA similarity value of 100% with
      Nocardioides luteus KCTC 9575T and Nocardioides albus JCM 5854. 'N. fulvus' IFO
      14399 shared its highest 16S rDNA similarity with Nocardioides sp. ATCC 39419 at
      99%. 'N. fulvus' IFO 14399 and Nocardioides sp. ATCC 39419 formed a phylogenetic
      lineage distinct from the genera Nocardioides and Aeromicrobium. 'Nocardioides
      thermolilacinus' strains IFO 14335T and IFO 14336 displayed a close relationship
      to the genus Streptomyces. From 16S rDNA sequence analyses, it is considered that
      some strains that have been attributed to the genus Nocardioides should be
      taxonomically re-evaluated.

PMID- 9542089
TI  - Emended description of Campylobacter sputorum and revision of its
      infrasubspecific (biovar) divisions, including C. sputorum biovar
      paraureolyticus, a urease-producing variant from cattle and humans.
AB  - A polyphasic taxonomic study of 15 bovine and human strains assigned to the
      catalase-negative, urease-positive campylobacter (CNUPC) group identified these
      bacteria as a novel, ureolytic biovar of Campylobacter sputorum for which we
      propose the name C. sputorum bv. paraureolyticus: suitable reference strains are
      LMG 11764 (human isolate) and LMG 17590 (= CCUG 37579, bovine isolate). The
      present study confirmed previous findings showing that the salient biochemical
      tests used to differentiate C. sputorum bv. sputorum from C. sputorum bv. bubulus
      are not reproducible; and that the absolute validity of source-specific biovars
      of the species is questionable. A correlation between the results of numerical
      analysis of protein profiles and the reaction of strains in certain enzyme tests
      was, however, noted. Therefore, it is proposed that the infrasubspecific (biovar)
      divisions of C. sputorum should be revised to include bv. sputorum for catalase
      negative strains; bv. fecalis for catalase-positive strains; and bv.
      paraureolyticus for urease-positive strains. Strains classified previously as bv.
      bubulus should be reclassified as bv. sputorum. The species description of C.
      sputorum is revised accordingly.

PMID- 9542090
TI  - A new leptospiral serovar, ngavi, in the Tarassovi serogroup isolated from
      Zimbabwe oxen.
AB  - Two strains of the genus Leptospira, belonging to serogroup Tarassovi, were
      isolated from kidneys of apparently healthy oxen slaughtered at an abattoir in
      Zimbabwe. Both strains belonged to the same serovar but could not be assigned to
      previously known serovars using the cross-agglutinin absorption test. The name
      ngavi is proposed for the new serovar containing these two strains; strain SBF 16
      is the reference strain. The Zimbabwe isolates showed some antigenic similarity
      to serovar gatuni when analyses were carried out using eight monoclonal
      antibodies, and had restriction patterns similar to those of serovars tarassovi,
      tunis, moldaviae and guidae when their chromosomal DNAs were analysed using RFLP
      analysis. The restriction patterns of the two strains could be distinguished from
      each other and from those of the four serovars when their Southern blots were
      hybridized with a probe synthesized from a repetitive sequence element cloned
      from serovar hardjo strain Hardjo-bovis.

PMID- 9542091
TI  - Fermentative degradation of 3-hydroxybenzoate in pure culture by a novel strictly
      anaerobic bacterium, Sporotomaculum hydroxybenzoicum gen. nov., sp. nov.
AB  - A strictly anaerobic bacterium, strain BT, from termite hindgut homogenates, was
      isolated in pure culture and grew on 3-hydroxybenzoate as sole source of carbon
      and energy. No other substrate tested was degraded, sulfate, sulfite,
      thiosulfate, nitrate, ferric iron, oxygen or fumarate were not reduced, and no
      electron transfer to partner organisms was observed. 3-Hydroxybenzoate was
      fermented to butyrate, acetate and CO2. Benzoate was detected in the culture
      supernatant as an intermediate. The isolate was a slightly motile,
      endosporeforming Gram-positive rod; 16S rDNA sequence analysis revealed a high
      similarity to members of the genus Desulfotomaculum. The G + C content of the DNA
      was 48 mol%. Strain BT differs from the members of the genus Desulfotomaculum
      significantly due to its lack of dissimilatory sulfate reduction, and is
      therefore described as the type strain of a new genus and species. Sporotomaculum
      hydroxybenzoicum gen. nov., sp. nov.

PMID- 9542093
TI  - Nocardia crassostreae sp. nov., the causal agent of nocardiosis in Pacific
      oysters.
AB  - Seven strains of bacteria were isolated from Pacific oysters, Crassostrea gigas,
      with a focal or systemic disease. The strains were aerobic, Gram-positive, acid
      fast, produced a mycelium which fragmented into irregular rod-like elements, had
      a peptidoglycan containing meso-diaminopimelic acid, arabinose and galactose as
      major sugars, mycolic acids with 46-58 carbon atoms and G + C-rich DNA. All of
      these properties are consistent with the classification of the organisms in the
      genus Nocardia. A partial sequence of the 16S rRNA gene of isolate NB4H was
      determined following isolation and cloning of the PCR-amplified gene. The
      sequence was aligned with those of representative mycolic-acid-containing taxa
      and a phylogenetic tree was generated using the neighbour-joining method. It was
      evident from the phylogenetic tree that the three strains tested, RB1, OB3P and
      NB4H, were identical and belonged to the Nocardia otitidiscaviarum rRNA sub
      group. The biochemical, chemical, morphological and physiological properties of
      the isolates were also essentially identical and served to distinguish them from
      representative nocardiae. It is, therefore, proposed that the strains isolated
      from the diseased Pacific oysters be assigned to a new species, Nocardia
      crassostreae. The type strain is NB4H (= ATCC 700418).

PMID- 9542092
TI  - Polaribacter gen. nov., with three new species, P. irgensii sp. nov., P.
      franzmannii sp. nov. and P. filamentus sp. nov., gas vacuolate polar marine
      bacteria of the Cytophaga-Flavobacterium-Bacteroides group and reclassification
      of 'Flectobacillus glomeratus' as Polaribacter glomeratus comb. nov.
AB  - Several psychrophilic, gas vacuolate strains of the Cytophage-Flavobacterium
      Bacteroides (CFB) phylogenetic group were isolated from sea ice and water from
      the Arctic and the Antarctic. The closest taxonomically defined species by 16S
      rRNA sequence analysis is 'Flectobacillus glomeratus'. However, 'Flc. glomeratus'
      is phylogenetically distant from the Flectobacillus type species, Flc. major. On
      the basis of phenotypic, genotypic and 16S rRNA sequence analyses we propose a
      new genus, Polaribacter, with three new species, Polaribacter irgensii strain 23
      P (ATCC 700398), Polaribacter franzmannii strain 301 (ATCC 700399) and
      Polaribacter filamentus strain 215 (ATCC 700397). P. filamentus is the type
      species of the genus. None of these species exhibits a cosmopolitan or bipolar
      distribution. This is the first taxonomic description of gas vacuolate bacteria
      in the CFB group. Additionally, we propose that 'Flc. glomeratus' be reclassified
      to the genus Polaribacter as P. glomeratus, comb. nov.

PMID- 9542094
TI  - Phenotypic diversity of Pseudoalteromonas citrea from different marine habitats
      and emendation of the description.
AB  - Four strains of marine, aerobic, agar-decomposing bacteria with one polar
      flagellum and with DNA G + C contents of 38.9-40.2 mol% were isolated from the
      Far-Eastern mussels Crenomytilus grayanus and Patinopecten yessoensis. These four
      strains were identified as Pseudoalteromonas; however, they were phenotypically
      different from species described previously according to carbon compound
      utilization tests and the BIOLOG identification system. High agar-decomposing
      activity was found in two strains, in one of which agarase, alpha-galactosidase,
      pustulanase and laminarinase had been detected. The level of DNA homology of
      three of the strains was 70-100%. The fourth isolate was genetically less related
      to the others (67% DNA relatedness) and phenotypically was more distant from
      other members of this group; however, all four strains were assigned to a single
      species genotypically. DNA from the strains isolated from mussels showed 40-45%
      genetic relatedness with the DNA of Alteromonas atlantica, 8-36% with DNA of
      Pseudoalteromonas haloplanktis subsp. haloplanktis, Pseudoalteromonas
      haloplanktis subsp. tetraodonis, Pseudoalteromonas undina, Pseudoalteromonas
      nigrifaciens and Pseudoalteromonasas carrageenovora, 53% with Pseudoalteromonas
      elyakovii, 32-48% with marine P. nigrifaciens from mussels and 14-16% with
      Alteromonas macleodii. The DNA-DNA hybridization data revealed that the levels of
      relatedness between the strains isolated and the type strains of
      Pseudoalteromonas citrea and Pseudoalteromonas fuliginea described recently were
      significant (95-85%). These results were confirmed by serological data employing
      polyclonal antibodies to cell surface antigens. The strains isolated from mussels
      were identified as P. citrea. The hybridization data showed that the name P.
      fuliginea Romanenko et al. 1994 should be recognized as a junior subjective
      synonym of P. citrea Gauthier 1977. A notable phenotypic diversity of P. citrea
      which might be a reflection of their ecological habitats is discussed.

PMID- 9542095
TI  - Phylogenetic characterization of the bacterium-like organism associated with
      marginal chlorosis of strawberry and proposition of a Candidatus taxon for the
      organism, 'Candidatus phlomobacter fragariae'.
AB  - Marginal chlorosis is a new disease of strawberry which was first seen in France
      in 1988. A phloem-restricted bacterium-like organism was found associated with
      the disease. Even though the organism could not be cultured and resembles in this
      way most other phloem-restricted pathogens, characterization was achieved from
      the sequence of its PCR-generated 16S rDNA, and comparison with other organisms.
      From these studies, the strawberry agent was found to be a new bacterium within
      group 3 of the gamma subclass of Proteobacteria, a group of Gram-negative
      bacteria including, in particular, insect symbionts or parasites as well as
      enterobacteria. Its closest relative, Arsenophonus nasoniae, is the causal agent
      of the son-killer trait in wasps. The two bacteria share 92% 16S rDNA sequence
      identity. We propose a Candidatus taxon for the marginal-chlorosis-associated
      bacterium, 'Candidatus Phlomobacter fragariae'.

PMID- 9542096
TI  - Sequences of the 16S rRNA genes and phylogeny of the goat mycoplasmas Mycoplasma
      adleri, Mycoplasma auris, Mycoplasma cottewii and Mycoplasma yeatsii.
AB  - The nucleotide sequences of the 16S rRNA genes from the type strains of four goat
      mycoplasmas, Mycoplasma adleri, Mycoplasma auris, Mycoplasma cottewii and
      Mycoplasma yeatsii, were determined by direct solid-phase DNA sequencing.
      Polymorphisms were found in two of the 16S rRNA gene sequences, showing the
      existence of two different rRNA operons. Three polymorphisms were found in M.
      adleri, and one was found in M. yeatsii. The sequence information was used for
      the construction of phylogenetic trees. M. adleri was included in the Mycoplasma
      lipophilum cluster within the hominis group. M. auris was comprised in the
      Mycoplasma hominis cluster of the hominis group. M. cottewii and M. yeatsii were
      found to be very closely related with only four nucleotide differences, and they
      grouped with Mycoplasma putrefaciens in the Mycoplasma mycoides cluster within
      the spiroplasma group. Sequencing of two field isolates of M. cottewii and M.
      yeatsii, geographically distant from the type strains, showed that the 16S rRNA
      gene from the field isolate of M. cottewii was identical to the one from the type
      strain. The field isolate of M. yeatsii had only two nucleotide differences to
      the type strain and these were present in only one of the two rRNA operons.
      Sequencing of the 16S rRNA genes from two unidentified mycoplasma isolates from
      Nepal indicated that they should both be regarded as M. auris strains.

PMID- 9542097
TI  - Classification of new phytoplasmas associated with diseases of strawberry in
      Florida, based on analysis of 16S rRNA and ribosomal protein gene operon
      sequences.
AB  - Strawberry plants exhibiting symptoms of stunting and abnormally small leaves
      were observed in production fields in central Florida, USA. Since the symptoms
      were suggestive of phytoplasma infection, plants were assayed for presence of
      phytoplasma by PCR amplification of 16S rDNA and ribosomal protein (rp) gene
      sequences. Amplification of phytoplasma-specific DNA sequences by PCR indicated
      infection of the diseased strawberry plants by phytoplasmas. RFLP analyses of
      amplified 16S rDNA revealed that the plants were infected by two mutually
      distinct phytoplasmas that differed from strawberry green petal phytoplasma
      (group 16Srl-C). Both phytoplasmas were members of 16S rRNA gene group I (16Srl).
      Based on RFLP analysis of amplified 16S rDNA and rp gene sequences, one was
      classified in group 16Srl subgroup I and new rp subgroup 16Srl-l(rp); its 16S
      rRNA-rp subgroup was designated 16Srl-K(rr-rp). The second phytoplasma
      represented a previously undescribed subgroup, designated K, in 16S rRNA group I
      but belonged to rp subgroup 16Srl-J(rp); this phytoplasma's 16S rRNA-rp subgroup
      was designated 16Srl-J(rr-rp). Results of RFLP analyses agreed with putative
      restriction site maps based on nucleotide sequences determined for the amplified
      16S rDNAs and rp gene operon DNAs. Further evidence indicated that the 16Srl-K(rr
      rp) strawberry phytoplasma, Mexican periwinkle virescence phytoplasma and stolbur
      phytoplasma shared sequence homologies that enabled amplification of DNA from all
      three by PCR using primers previously designed as stolbur-specific.

PMID- 9542099
TI  - Fellomyces ogasawarensis sp. nov. and Fellomyces distylii sp. nov., yeasts
      isolated from a plant in Japan.
AB  - Fellomyces ogasawarensis and Fellomyces distylii, new yeast species isolated from
      a dead leaf of a plant (Distylium-lepidotum Nakai, family Hamamelidaceae)
      collected in the Ogasawara Islands, isolated islands in the Pacific Ocean about
      1000 km south of Japan, are described. The phylogenetic relationship of F.
      ogasawarensis and F. distylii with other members of the genus Fellomyces was
      estimated from 18S rRNA gene sequence analysis. The type strain of F.
      ogasawarensis is strain OK-81 (= JCM 9861) and that of F. distylii is strain OK
      83 (= JCM 9862).

PMID- 9542098
TI  - Differentiation and species identification of yeasts using PCR.
AB  - A PCR-based method has been developed that permits both intraspecies
      differentiation and species identification of yeast isolates. Oligonucleotide
      primers that are complementary to intron splice sites were used to produce PCR
      fingerprints that display polymorphisms between different species of indigenous
      wine yeasts. Although polymorphisms existed between isolates of the same species,
      the banding patterns shared several amplification products that allowed species
      identification. Importantly, the method was able to distinguish between species
      of the closely related Saccharomyces sensu stricto yeasts. In two cases where
      isolates could not be positively identified there was discrepancy between the
      phenetic and phylogenetic species concept. The method has applications in yeast
      ecological studies, enabling the rapid grouping of isolates with related genomes
      and the investigation of population dynamics of strains of the same species.

PMID- 9542100
TI  - Phylogenetic analysis of the Saccharomyces cerevisiae group based on
      polymorphisms of rDNA spacer sequences.
AB  - The phylogenetic relationships between species of yeasts assigned to the
      Saccharomyces sensu stricto group, which includes Saccharomyces cerevisiae and
      Saccharomyces bayanus, were studied together with Saccharomyces pastorianus and
      Saccharomyces paradoxus. The experimental approaches used were RFLP analysis of
      the PCR-amplified rDNA internal transcribed spacer (ITS) and intergenic spacer,
      and total ITS sequence analysis. Both RFLP and sequence analyses gave fairly
      similar results. The gene trees generated with either of the two data sets showed
      the distribution of the yeasts into two major, well-separated, phylogenetic
      clusters called 'cerevisiae' and 'bayanus'. The 'cerevisiae' cluster included the
      S. cerevisiae type strain, together with most of the species (16 out of 23),
      whereas the 'bayanus' cluster included the remaining seven type strains.
      Therefore, analysis of rDNA sequences confirmed S. cerevisiae and S. bayanus as
      two well-defined taxa. However, S. pastorianus and S. paradoxus, the two other
      usually accepted taxa of the now-defined Saccharomyces sensu stricto complex,
      could not be clearly separated from S. bayanus and S. cerevisiae, respectively.
      However, in both PCR-RFLP and ITS sequence analyses, S. paradoxus had the
      outermost position in the 'cerevisiae' cluster. PCR-RFLP analysis of the
      ribosomal spacer sequences was also carried out on 26 Saccharomyces strains
      isolated in various wine-growing regions of France in an attempt to clarify their
      positions in the Saccharomyces phylogenetic tree. Compared to the diversity of
      the Saccharomyces type strains, less genetic diversity was detected among these
      yeasts and several of them exhibited identical RFLP patterns. Most of the wine
      yeast strains (16 out of 26) were closely related to each other and were found
      within the 'cerevisiae' cluster. The remaining 10 wine yeast strains branched
      within the 'bayanus' cluster. PCR-RFLP analysis of ribosomal spacer sequences
      thus appears to be a useful and appropriate method for the correct
      characterization of Saccharomyces yeast strains used in food processing.

PMID- 9542101
TI  - Phylogenetic position of rare human mycoplasmas, Mycoplasma faucium, M. buccale,
      M. primatum and M. spermatophilum, based on 16S rRNA gene sequences.
AB  - The nucleotide sequence of the 16S rRNA genes of four rare human mycoplasma
      species, Mycoplasma faucium, M. buccale, M. primatum and M. spermatophilum, were
      partially sequenced and compared to published rRNA genes of mycoplasmas to
      determine their position in the Mollicutes phylogenetic tree. Nucleotide sequence
      motif and overall similarities allowed positioning of these mycoplasmas in the
      hominis phylogenetic group, as defined by Weisburg et al. [Weisburg, W. G.,
      Tully, J. G., Rose, D. L. & 9 other authors (1989). J Bacteriol 171, 6455-6467].
      Furthermore, these mycoplasmas could be clustered into two different subdivisions
      of the hominis group: (i) M. faucium and M. buccale were found to be included in
      the M. fermentans subdivision, and (ii) M. primatum and M. spermatophilum were
      included in the M. hominis one. Variable regions of the 16S rRNA genes were used
      to determine specific PCR primers to detect and identify M. faucium.

PMID- 9542102
TI  - Desulfovibrio aespoeensis sp. nov., a mesophilic sulfate-reducing bacterium from
      deep groundwater at Aspo hard rock laboratory, Sweden.
AB  - A sulfate-reducing bacterium, strain Aspo-2, was isolated from granitic
      groundwater sampled at a depth of 600 m. This and other strains of SRB frequently
      occur in the deep granitic rock aquifers studied. On the basis of its
      morphological, physiological and genotypical properties, and its unique habitat,
      we propose strain Aspo-2 as a new species of the genus Desulfovibrio,
      Desulfovibrio aespoeensis (DSM 10631T).

PMID- 9542103
TI  - Burkholderia thailandensis sp. nov., a Burkholderia pseudomallei-like species.
AB  - The presence of a Burkholderia pseudomallei-like species based upon the
      significant genotypic and phenotypic dissimilarities exhibited between these
      organisms and true B. pseudomallei strains has been reported previously. In this
      study, a comprehensive 16S rDNA-based phylogenetic analysis further supports the
      existence of this newly described Burkholderia species for which the name
      Burkholderia thailandensis sp. nov. is proposed.

PMID- 9542104
TI  - Is natural genetic transformation a mechanism of horizontal gene transfer in
      Yersinia?
AB  - We investigated the capacity of different Yersinia strains with emphasis to
      Yersinia enterocolitica to take up and incorporate DNA by natural genetic
      transformation. Our studies were initiated by the observation of partial homology
      between the virulence plasmid of a pathogenic Y. enterocolitica strain (O: 3,
      biovar 4) and plasmids indiginous to different a pathogenic Y. enterocolitica
      biovar 1A strains revealed by hybridization studies. Furthermore, an observation
      of natural genetic transformation in a strain of Y. enterocolitica has been
      published by CALLAHAN and KOROMA (1979). To detect an uptake and incorporation of
      DNA, we incubated potential recipient strains with naked DNA under varying
      experimental conditions. The parameters tested were--the recipient strain,--the
      markers used to detect a DNA transfer,--the condition of the transforming DNA,-
      the nutrient availability,--the temperature,--the growth phase, and--the
      influence of stress. In our experiments, we could not identify conditions under
      which Y. enterocolitica could be naturally transformed. We thus conclude that
      natural transformation is unlikely to be an important mechanism for horizontal
      gene transfer in Yersinia.

PMID- 9542105
TI  - Depression by miconazole of heat-induced respiratory-deficiency in Saccharomyces
      cerevisiae.
AB  - Miconazole, at 0.2 microM, decreased, by two orders of magnitude, the specific
      mutation rate of Saccharomyces cerevisiae to respiratory-deficient mutants
      (petites), which had been induced at either 37 degrees C or 39 degrees C.
      Identical concentrations of ketoconazole did not change the mutation rate. The
      results fit in the mechanisms of action which have been proposed for imidazole
      antimycotics, and constitute further support for the hypothesis that the targets
      of thermal death, in petite-positive associately-profiled yeasts, lie in the
      mitochondria.

PMID- 9542106
TI  - Unique appendages associated with spores of Bacillus cereus isolates.
AB  - Electron microscopic observations revealed the presence of a new type of large
      appendage on the spores of two Bacillus cereus strains isolated from
      phylloplanes. The appendages were thin and sword-like in shape, having the sizes
      of 1.5 to 2.8 microns in length and 0.03 to 0.6 micron in width. There were no
      core or sheath structures in these appendages. The number of appendages on a
      spore ranged from three to more than twenty, radiating from the swelling on one
      end of the exosporium. These appendages gave a unique octopus- or jellyfish-like
      feature to the spores.

PMID- 9542107
TI  - Occurrence of thermoregulation of genes involved in coronatine biosynthesis among
      various Pseudomonas syringae strains.
AB  - Several pathovars of Pseudomonas syringae produce the polyketide phytotoxin
      coronatine (COR). In the bacterial blight pathogen of soybean, P. syringae pv.
      glycinea PG4180, COR is produced at high levels at 18 degrees C whereas no toxin
      is synthesized at 28 degrees C. Previously, activation of three promoters inside
      the COR biosynthetic gene cluster by a modified two-component regulatory system
      was shown to influence thermoregulation of COR biosynthesis. Using phenotypic
      determination of COR synthesis, a transcriptional reporter gene fusion, and
      Western blot analysis, we screened a representative number of natural isolates of
      P. syringae for effects of temperature on expression of cmaA, cmaB, and cmaT,
      which encode enzymes involved in the biosynthesis of COR. Thermoregulation of
      cmaABT expression was frequent among the tested strains. However, intensities of
      the temperature effects varied widely. Coronatine synsthesis was found to differ
      at up to six-fold among COR producing strains. There was no strain which
      synthesized COR at 28 degrees C although some of them showed increased basal
      cmaABT promoter activities at this temperature. Transcriptional fusions between
      the cmaABT promoter and a promoterless reporter gene were found to be down
      regulated at 28 degrees C only in COR producing strains but not in the non
      producing strains tested. The geographic origin of the bacterial strains did not
      influence the occurrence of temperature-dependent gene expression.

PMID- 9542108
TI  - Adaptation and reutilization of Candida guilliermondii cells for xylitol
      production in bagasse hydrolysate.
AB  - The xylitol productivity increased by about 15% with the use of cells of Candida
      guilliermondii FTI 20037 previously recycled through four consecutive batch
      cultures and adapted to the sugar cane bagasse hemicellulosic hydrolysate.
      Furthermore, the more concentrated the hydrolysate, the more necessary was the
      adaptation of the cells, owing to the presence of toxic substances at high
      concentration which inhibited the xylose-xylitol conversion by the yeast.

PMID- 9542111
TI  - High-performance liquid chromatography study of stereospecific microsomal enzymes
      catalysing the reduction of a potential cytostatic drug, oracin. Interspecies
      comparison.
AB  - One of the main metabolites of oracin (I) ?6-[2-(2-hydroxyethyl)aminoethyl]-5,11
      dioxo-5,6-dihydro-11H-indeno[1,2- c] isoquinoline?, a potential cytostatic drug,
      is 11-dihydrooracin (II) ?(+),(-)-6-[2-(2-hydroxyethyl)aminoethyl]-5-oxo-11
      hydroxy-5,6-dihydro-1 1H- indeno[1,2-c]isoquinoline?, a metabolite formed by the
      reduction of oracin's pro-chiral centre on C 11. This metabolite has been found
      in all laboratory species in vitro and in vivo and it constitutes the main
      metabolite in man. The stereospecificity of reducing enzymes participating in the
      oracin biotransformation pathway was investigated using microsomal preparations
      from standard laboratory animals. Enzyme stereospecificity has been defined as
      preferential formation by the enzyme of the (+) or (-) stereoisomer of II.
      Significant interspecies differences were observed in the stereospecificity of
      the respective biotransformation enzymes. HPLC quantitative determinations of
      both enantiomers were performed using a Chiralcel OD-R column as chiral
      stationary phase with excellent resolution and stability.

PMID- 9542112
TI  - Determination of drugs in biological fluids by high-performance liquid
      chromatography with on-line sample processing.
AB  - An automated two column HPLC system with the new packing material LiChrospher RP
      18 ADS (alkyl-diol-silica) was tested for the determination of several drugs and
      metabolites (talinolol, celiprolol, metoprolol, oxprenolol, triamterene,
      trimethoprim, tiracizine, articaine, detajmium, ajmaline, lamotrigine) in various
      biological fluids (serum, urine, intestinal aspirates, supernatants of cell
      cultures and supernatants after protein denaturation). The method allows the
      direct injection of biological fluids into a reversed-phase HPLC system and on
      line clean-up and sample enrichment by a column-switching technique. Precision,
      accuracy and sensitivity were similar to conventional assays as described in the
      literature. With this new method it was possible to measure drug concentrations
      in various biological fluids without changing the sample preparation procedure.
      In some cases an additional sample preparation like protein denaturation or solid
      phase extraction was advantageous to enhance the sensitivity of the method and
      the life-time of the ADS column.

PMID- 9542113
TI  - Determination of several N-methyl-D-aspartate receptor blockers in plasma and
      brain by a selective high-performance liquid chromatographic method with column
      switching.
AB  - A general procedure is presented for the determination of several N-methyl-D
      aspartate (NMDA) receptor open-channel and subtype-selective blockers, which have
      been evaluated and developed as neuroprotective drugs for the treatment of brain
      stroke and trauma. The method involves deproteination of plasma with ethanol, or
      homogenization of brain samples in ethanol, dilution of the supernatant with
      ammonium acetate and direct injection into an HPLC column-switching system.
      Although the investigated NMDA receptor blockers are all tertiary amines, they
      have quite different structures. However, they are all concentrated on the first
      column (Purospher RP-18, 125 x 4 mm), whereas polar interfering compounds are
      washed out with 1% ammonium acetate-acetic acid-acetonitrile (100:1:5, v/v/v).
      Due to the special selectivity of the Purospher RP-18 material, the analytes and
      the internal standard are then selectively eluted with 25% acetonitrile (without
      any buffer in the mobile phase) and transferred to the analytical column
      (Superspher 60 RP-select B, 250 x 4 mm), where they are separated by gradient
      elution and detected by UV or fluorescence detection. The low degree of
      interference allowed the development of sensitive methods with quantification
      limits of 5 ng/ml for animal plasma (0.4 ml used), 0.5 ng/ml for human plasma (1
      ml used) and 50 ng/g for brain tissue (200 mg used).

PMID- 9542114
TI  - High-performance liquid chromatographic method with coulometric detection for the
      determination of buspirone in human plasma by means of a column-switching
      technique.
AB  - A reversed-phase high-performance liquid chromatographic method with
      electrochemical detection has been developed for the determination of buspirone
      from human plasma. The separation was carried out by using a Supelcosil ABZ+ plus
      C18 reversed-phase column and 0.05 M potassium dihydrogenphosphate (pH 6.5)
      acetonitrile (7:3, v/v) as the mobile phase. The compounds were detected by
      coulometry. Buspirone and the internal standard were extracted from the human
      plasma using Bond-Elut C18 solid-phase extraction cartridges. Following removal
      of the the highly lipophilic plasma components we applied a column-switching
      technique which reduced the duration of HPLC measurement from 60 min to 15 min.
      The limit of quantitation was found to be 100 pg/ml plasma.

PMID- 9542115
TI  - Determination of sedatives and anesthetics in plasma by liquid chromatography
      mass spectrometry with a desalting system.
AB  - Though liquid chromatography-mass spectrometry (LC-MS) is a powerful tool for
      analysis of drugs and their metabolites, it does not allow the use of a non
      volatile buffer such as phosphate buffer. We used a column-switching desalting
      system in combination with atmospheric pressure chemical ionization LC-MS for
      analysis of sedatives and anaesthetics. The drugs examined were flumazenil,
      butorphanol, midazolam, lorazepam, phenobarbital and flunitrazepam. The
      separation was carried out on a reversed-phase column using acetonitrile-0.1 M
      phosphate buffer as a mobile phase. The mass spectra are almost the same as those
      obtained by direct analysis and the molecular ions were clearly observed. In the
      analysis, phosphate buffer was completely removed with the trapping column and
      did not interfere with ionization of the drugs in MS. The chiral separation of
      lorazepam was achieved on a chiral column with UV, optical rotatory detection and
      MS. This method is sufficiently sensitive and accurate for the pharmacokinetic
      studies of these drugs in biological samples.

PMID- 9542116
TI  - Determination of fenbendazole, praziquantel and pyrantel pamoate in dog plasma by
      high-performance liquid chromatography.
AB  - Simple and rapid high-performance liquid chromatographic methods were developed
      for the determination of fenbendazole, praziquantel and pyrantel pamoate in dog
      plasma. The combination of these drugs is the most powerful treatment against
      most types of worms. Blood plasma samples obtained in a pharmacokinetic trial
      were prepared using solid-phase extraction. Fenbendazole and praziquantel were
      analyzed simultaneously by reversed-phase high-performance liquid chromatography
      on an octadecyl-modified silica stationary phase employing acetonitrile-phosphate
      buffer (pH 3.0) eluent and ultraviolet detection at 220 nm. Pyrantel was analyzed
      separately on a base-deactivated reversed-phase column using methanol
      tetrahydrofuran-ammonium acetate buffer (pH 4.6) eluent and ultraviolet detection
      at 317 nm. Average recoveries for fenbendazole, praziquantel and pyrantel pamoate
      were 76.8, 93.4 and 90.5%, respectively. Limits of quantitation were in the range
      of 15-25 ng/ml plasma.

PMID- 9542117
TI  - Determination of morphine in urine by solid-phase immunoextraction and high
      performance liquid chromatography with electrochemical detection.
AB  - The analysis of morphine in biological fluids is of vital interest in monitoring
      opiate abuse and in drug abuse research. Although methods for analysis of
      morphine and its metabolites are well established, studies are still being
      carried out to improve sample preparation procedures as well as detection levels
      of morphine in biological samples. In this study, morphine-specific
      immunosorbents were developed to concentrate morphine prior to HPLC analysis.
      Urine (0.1 ml) was diluted 10-fold with phosphate-buffered saline, pH 7.4 (PBS),
      loaded onto a solid-phase immunoextraction column and washed with 15 ml PBS
      followed by elution with 2 ml of elution buffer (40% ethanol in PBS, pH 4). The
      eluted fraction was analysed for morphine by HPLC-electrochemical detection using
      a cyanopropyl (CN) analytical column with 25% acetonitrile in phosphate buffer
      sodium lauryl sulphate, pH 2.4 as the mobile phase. Duration of the extraction
      procedure was approximately 40 min. Calibration graphs were linear from 100 ng ml
      1 to 500 ng ml-1 in urine. The inter-assay R.S.D. was < 10% and the recovery of
      morphine from urine was > 98%. Immunocolumns demonstrated remarkably high
      specificity towards morphine showing minimal binding with other opiate
      metabolites such as codeine, normorphine, norcodeine, morphine-3-glucuronide,
      morphine-6-glucuronide.

PMID- 9542118
TI  - Direct injection of large volumes of plasma/serum on a new biocompatible
      extraction column for the determination of atenolol, propranolol and ibuprofen.
      Mechanisms for the improvement of chromatographic performance.
AB  - Very large volumes of serum/plasma can be directly injected to a new extraction
      column based on particles with a biocompatible outer surface and C18 groups
      within the pores. The biocompatibility has been obtained by attaching the human
      plasma protein alpha 1-acid glycoprotein to the outer surface of the particles.
      The pores are small enough to exclude the plasma protein molecules. Atenolol and
      propranolol were extracted on the extraction column as ion-pair with
      octanesulfonic acid as the counterion. The same counterion was used in the
      analytical mobile phase. A strong improvement of the recovery can be obtained
      using octanesulfonic acid as counterion in the extraction mobile phase. The
      recovery of atenolol increased from about 53.5% to about 93.4% using
      octanesulfonic acid as counterion. The chromatographic performance was also
      strongly affected by chromatography of the basic drugs as ion-pair with
      octanesulfonic acid. The improvement was due to trapping in a smaller section of
      the extraction column and enrichment of the drug on top of the analytical column.
      The enrichment was due to the transfer of the analyte to the analytical column in
      a zone with high concentration of counterion. Furthermore, the sample zone is
      compressed during the migration on the analytical column. The compression effect
      was caused by the counterion zone, migrating in front of the sample zone, giving
      the analyte higher retention on the front side than on the back side of the
      sample zone. Displacement of protein bound drug (ibuprofen) by addition of
      octanoic acid, was tested in order to study the influence on the recovery and the
      effect on the chromatographic performance. The recovery was improved and the
      chromatographic performance was greatly improved. The improvement obtained on the
      separation efficiency of ibuprofen was due to enrichment on top of the analytical
      column and compression during the migration through the analytical column. The
      enrichment was caused by a reduction of pH in the sample--octanoic acid zone
      transferred from the extraction column. The octanoic acid zone migrated in front
      of the sample zone giving a lower pH in front of the ibuprofen zone than behind.
      Thus, higher retention occurred in front of than behind the sample zone, which
      gave rise to compression. The methods developed for atenolol, propranolol and
      ibuprofen could be used for the determination of serum/plasma concentrations
      after single doses of the drugs with very high accuracy and precision. Linear
      calibration graphs were obtained and the r values were > or = 0.9999.

PMID- 9542119
TI  - Validated liquid chromatographic method for the determination of N-3-(2,2,5,5
      tetramethyl-3-pirrolin-3-carboxamidopropylphthalimide hydrochloride), a novel
      antiarrhythmic agent in human plasma.
AB  - A simple high-performance liquid chromatographic method with ultraviolet
      absorbance detection has been developed to determine the concentration of N-3
      (2,2,5,5-tetramethyl-3-pirrolin-3-carboxamidopropylphthalim ide hydrochloride; A
      2545), a new antiarrhythmic agent from human plasma. Separation of the
      investigated compound and internal standard was achieved on a Nucleosil 7 C18
      column with a 0.01-M potassium dihydrogenphosphate buffer (pH 2.5)-methanol
      (60:40, v/v) mobile phase. The detection was performed at 220 nm. During the
      determinations, buspirone served as the internal standard. The compounds were
      isolated from plasma on a Bakerbond C18 solid-phase extraction cartridge and the
      mean absolute recovery was 92.9%. The limit of quantitation was found to be 10
      ng/ml. The bioanalytical method was validated with respect to linearity, within-
      and between-day accuracy and precision, system suitability and stability. All
      validated parameters were found to be within the internationally required limits.
      The developed analytical method for A-2545 was found to be suitable for
      application in pharmacokinetic studies and for human drug monitoring.

PMID- 9542120
TI  - High-performance liquid chromatography methods for the separation and
      quantitation of spironolactone and its degradation products in aqueous
      formulations and of its metabolites in rat serum.
AB  - HPLC assays have been developed for the determination of spironolactone and its
      degradation products 7 alpha-thiospirolactone and canrenone in aqueous solutions
      of beta-cyclodextrins and for the determination of spironolactone and its
      metabolites 7 alpha-thiospirolactone, 7 alpha-thiomethylspirolactone, 6 beta
      hydroxy-7 alpha-thiomethylspirolactone and canrenone in rat serum samples. Both
      methods were well suited for their respective applications, i.e., studying the
      stability of spironolactone in liquid formulations of beta-cyclodextrins and the
      oral absorption of spironolactone in rats. The HPLC method developed for
      spironolactone and its metabolites in rat serum requires very small volumes of
      serum making it possible to take several blood samples over a period of time.

PMID- 9542121
TI  - Determination of a new polymer-bound paclitaxel derivative (PNU 166945), free
      paclitaxel and 7-epipaclitaxel in dog plasma and urine by reversed-phase high
      performance liquid chromatography with UV detection.
AB  - A sensitive and selective high-performance liquid chromatographic method for the
      determination of PNU 166945, a new polymer-bound paclitaxel derivative, free
      paclitaxel and 7-epipaclitaxel in dog plasma and urine has been developed. The
      method involves a solid-phase extraction of free paclitaxel and its possible
      degradation product 7-epipaclitaxel from plasma and urine, previously buffered
      with an equal volume of 0.05 M or 1 M KH2PO4 respectively, on 1-ml cyanopropyl
      columns. Cartridges elution was performed with the mobile phase, 0.05 M (pH 4.6)
      monobasic potassium phosphate-acetonitrile mixture (45:55, v/v). The samples were
      chromatographed on a reversed-phase octyl 4-microns column with UV detection at
      229 nm. The retention times of paclitaxel and 7-epipaclitaxel were about 14 and
      22 min, respectively. Determination of total paclitaxel (free + polymer-bound)
      was performed after release of paclitaxel from the polymeric carrier by chemical
      hydrolysis at room temperature (22 degrees C) for 20 h. After addition of 0.5 ml
      of methanol-0.1 M KH2PO4 mixture (50:50, v/v, pH = 7.5) to 0.5 ml of plasma or
      urine, paclitaxel was analysed as described above. PNU 166945 concentration was
      then determined by subtraction of free from total paclitaxel. The linearity,
      precision, accuracy and recovery of the method were evaluated. The limit of
      quantitation of the method was 5 ng/ml for biological fluid for paclitaxel and 7
      epipaclitaxel and 20 ng/ml for PNU 166945 (as paclitaxel equivalent).

PMID- 9542122
TI  - Determination of furanochromones and pyranocoumarins in drugs and Ammi visnaga
      fruits by combined solid-phase extraction-high-performance liquid chromatography
      and thin-layer chromatography-high-performance liquid chromatography.
AB  - A new, simple and rapid solid-phase extraction method for the determination of
      furanochromones and pyranocoumarins in Ammi visnaga L. fruits and pharmaceuticals
      by reversed-phase high-performance liquid chromatography (RP-HPLC) was developed.
      The isolation of compounds examined was carried out on octadecyl BakerBond SPE
      columns using various concentrations of methanol, acetonitrile and
      tetrahydrofuran in water. High and reproducible recoveries were obtained. To
      compare the results of quantitative analysis a preparative TLC procedure was also
      elaborated and carried out.

PMID- 9542123
TI  - Simultaneous determination of total and extracellular concentrations of the amino
      acid neurotransmitters in cat visual cortex by microbore liquid chromatography
      and electrochemical detection.
AB  - To investigate the influence of a partial sensory deprivation on the total and
      extracellular concentration of the amino acid neurotransmitters in cat visual
      cortex, two microbore HPLC methods were developed for the simultaneous
      determination of aspartate, glutamate, glycine, taurine and gamma-aminobutyric
      acid in cat brain extracts or microdialysis samples. For the determination of the
      total neurotransmitter concentrations in the visual cortex, the brains were
      quickly frozen and 200-microns cryostat sections were made. From these sections
      tissue samples of 2 x 2 mm2 containing the six cortical layers were dissected out
      of the central and peripheral parts of area 17. After homogenisation and
      centrifugation, the supernatants were used for quantitative amino acid analysis
      using an o-phthalaldehyde-tert.-butylthiol pre-column derivatisation HPLC
      gradient elution method on a microbore column (100 x 1 mm I.D.; C8) and single
      electrochemical detection. Microdialysis samples from area 17 were obtained every
      15 min using 2-mm probes perfused with synthetic cerebrospinal fluid at a flow
      rate of 1 microliter/min. After o-phthalaldehyde-tert.-butylthiol derivatisation
      they were analysed on a microbore column by isocratic elution and dual
      electrochemical detection. The instrumentation and the different separation
      parameters were optimised and standard curve, recovery, analytical precision and
      detection limits for each neurotransmitter were determined.

PMID- 9542125
TI  - Removal of the fluorescent 4-(aminosulfonyl)-2,1,3-benzoxadiazole label from
      cysteine-containing peptides.
AB  - The complete removal of the fluorescent cysteine derivative 4-(aminosulfonyl)-7
      fluoro-2,1,3-benzoxadiazole (ABD-F) from an intact protein has not been
      demonstrated even after extended treatment with a reducing agent. It has been
      suggested that this may be due to incomplete denaturation under the conditions
      employed. We were interested in investigating this phenomenon utilizing small
      peptides containing individual ABD-labeled cysteine residues. After incubating
      the fluorescent peptides in the presence of a reductant, it was shown that the
      ABD label could be completely removed from all of the cysteine-containing
      peptides investigated. Therefore, delabeling irreversibility is due to residual
      structure in proteins. Electrospray ionization mass spectrometry (ESI-MS) was
      used to determine the molecular mass of each peptide after removal of the ABD
      lavel. The ESI-MS data were consistent with the generation of a free sulfhydryl.
      The generation of the free sulfhydryl was further substantiated when a delabeled
      peptide was completely relabeled with ABD-F in the absence of reductant.

PMID- 9542124
TI  - Urinary excretion measurement of cysteine and homocysteine in the form of their S
      pyridinium derivatives by high-performance liquid chromatography with ultraviolet
      detection.
AB  - Several human diseases, in particular metabolic disorders, often lead to the
      accumulation of characteristic metabolites in plasma, urine and cells. The
      selected diseases of this type include cystinuria and homocystinuria. In the
      typical laboratory diagnosis of these two diseases, a positive nitroprusside test
      is followed by quantitative analysis of urine cysteine and homocysteine in order
      to differentiate between cystinuria and homocystinuria. A sensitive and
      reproducible assay for total urine cysteine and homocysteine has been developed.
      The essential steps in the assay include conversion of disulphides to free thiols
      with tributylphosphine, conjugation of the thiols with 2-chloro-1-methyl
      pyridinium iodide, separation of S-pyridinium derivatives of cysteine and
      homocysteine from other endogenous urine thiol derivatives by reversed-phase high
      performance liquid chromatography, and detection and quantitation by
      spectrophotometry. The method has a sensitivity of 4 pmol and is reproducible,
      intra- and inter-day coefficients of variation are from 1.37 to 4.14% and from
      2.38 to 5.01%, respectively. The mean concentration of total urine cysteine and
      homocysteine in healthy donors (7 men and 7 women) were for women. 92.0 +/- 45.8
      and 16.4 +/- 4.8 respectively, and for men 120.9 +/- 46.6 and 21.5 +/- 7.4
      nmol/ml, respectively. Total urine homocysteine represents approximately 17.7% of
      cysteine in the urine of normal individuals.

PMID- 9542126
TI  - Effect of porous structure of macroporous polymer supports on resolution in high
      performance membrane chromatography of proteins.
AB  - The effect of porous structures of 2-mm thick diethylamine functionalized
      monolithic polymethacrylate discs on their chromatographic behavior in ion
      exchange mode has been studied. Discs with small pores did not perform well
      because they exhibited high back pressure and substantial peak broadening. Discs
      characterized with pores larger than 1,000 nm did not provide good separations
      either because the time required for some protein molecules to traverse the
      length across the pore to reach the wall for adsorption/desorption process that
      is essential for the separation may be longer than their residence time within
      the matrix. Optimum pore size is centered at about 700 nm. Excellent separations
      have been achieved with these discs even at very steep gradients and high flow
      rates which allow to shorten the separation times substantially.

PMID- 9542127
TI  - Fast isolation of protein receptors from streptococci G by means of macroporous
      affinity discs.
AB  - A fast affinity method for the semi-preparative isolation of recombinant Protein
      G from E. coli cell lysate is proposed. Rigid, macroporous affinity discs based
      on a glycidyl methacrylate-co-ethylene dimethacrylate polymer were used as
      chromatographic supports. The specific ligands (here human immunoglobulin G,
      hIgG) were immobilized by the one-step reaction between native epoxy groups of
      the polymer surface and epsilon-amino groups of the IgG molecules. No
      intermediate spacer was necessary to reach full biological activity of the
      ligand. The globular affinity ligands are located directly on the pore wall
      surface and are thereby freely accessible to target molecules (here Protein G)
      migrating with the mobile phase through the pores. It is shown that the
      conditions chosen for the hIgG immobilization do not involve an active site of
      the protein and thus do not bias the formation of the affinity complex.
      Chromatographically determined constants of dissociation of hIgG-Protein G
      affinity complexes confirm the high selectivity of this separation method. Two
      different aspects of the affinity separation are discussed, which differ mostly
      in terms of scale. In disc chromatography, high volumetric flow velocities are
      possible because of the small backpressure. Since in addition the mass transfer
      is more efficient, it becomes possible to achieve very short analysis times. The
      discs proposed can be used in a single-step enrichment of Protein G from lysates
      of non-pathogenic E. coli. Gel electrophoresis data are used to demonstrate the
      high degree of purity achieved for the final product.

PMID- 9542128
TI  - Accelerated recombinant protein purification process development automated,
      robotics-based integration of chromatographic purification and analysis.
AB  - Recovery of recombinant proteins from endogenous, host molecules can be an
      experimentally intensive and time-consuming task. Often the time to analyze
      material during development of recovery procedures is the rate-limiting step.
      Nowadays, modern techniques and equipment are being specifically engineered to
      make this effort much more efficient. We present a case study to illustrate how a
      new, automation tool, designed for easy, systematic methods development, can be
      used for very rapid process and analytical optimization. This tool uses robotics
      to integrate process development with rapid LC-based analysis requiring no user
      intervention. The methods and procedures described can be generalized to any
      recombinant protein recovery campaign.

PMID- 9542129
TI  - Rapid reversed-phase high-performance liquid chromatography method for
      quantitation, at high pH, of the recombinant apolipoprotein A-IMilano in
      Escherichia coli fermentation broth.
AB  - An automated reversed-phase high-performance liquid chromatography method for
      quantitative determination of recombinant apolipoprotein A-IMilano (r-Apo A-IM)
      in E. coli fermentation broth has been developed and evaluated. The use of a
      unique matrix (Poros IIR/H) makes it possible to achieve rapid separation and
      good resolution at high pH. The r-Apo A-IM-containing fraction is well separated
      from other proteins allowing a reliable quantification. The automation and high
      sample throughput of this method makes it very useful for routine determination
      of r-Apo A-IM in fermentation broth and in eluates from the various purfication
      steps. With suitable modifications and adaptions this method is likely to be
      useful for similar rapid analytical determination of recombinant proteins in
      complex solutions.

PMID- 9542130
TI  - Micro-sequencing strategies for the human A33 antigen, a novel surface
      glycoprotein of human gastrointestinal epithelium.
AB  - Monoclonal antibody (mAb) A33, which recognizes a M(r) approximately 43,000
      differentiation antigen (A33) expressed in normal human colonic and small bowel
      epithelium as well as in 95% of colon cancers, shows specific targeting of colon
      cancer in humans and is currently being evaluated for clinical use. Here, we
      describe strategies for the purification and structural analysis of the A33
      antigen from the human colorectal carcinoma cell lines LIM1215 and SW1222. Edman
      degradation of the intact protein and nine peptides, derived by proteolytic
      digestion of the A33 antigen with Asp-N endoproteinase, thermolysin, trypsin and
      pepsin followed by micropreparative reversed-phase high-performance liquid
      chromatography, allowed the unambiguous sequence assignment of 153 amino acid
      residues; these data reveal one N-glycosylation sequeon in Asp-N endoproteinase
      peptide D4, and a disulfide linkage between peptides D1 and D4. This amino acid
      sequence information has facilitated the cloning and subsequent sequencing of a
      cDNA for the A33 antigen which demonstrates that it is a novel human cell surface
      molecule of the immunoglobulin superfamily.

PMID- 9542131
TI  - Nitrite/nitrate balance during photoinduced cerebral ischemia in the rat
      determined by high-performance liquid chromatography with UV and electrochemical
      detection.
AB  - A specific and simple method for the direct simultaneous detection of
      extracellular nitrite (NO2-) and nitrate (NO3-) has been developed, using high
      performance liquid chromatography separation with UV and electrochemical
      detection in series. These stable endproducts of nitric oxide (NO.) were
      determined in dialysis perfusate obtained through in vivo brain microdialysis
      during and after experimental photoinduced cerebral ischemia in rats. The
      chromatographic conditions were optimized with a reversed-phase column (250 x 46
      mm) using 10 mM n-octylamine pH 6.0 as a mobile phase. Absorbance was measured at
      220 nm for NO3- detection; electrochemical detection was performed at +0.7 V for
      NO2- evaluation. This assay system holds the advantages of in vivo consecutive
      measurements, high precision, good reproducibility, technical simplicity, fast
      response (about 7 min), and wide availability.

PMID- 9542132
TI  - Improved ion chromatography-integrated pulsed amperometric detection method for
      the evaluation of biogenic amines in food of vegetable or animal origin and in
      fermented foods.
AB  - An improved method for the simultaneous determination of underivatized biogenic
      amines, cadaverine, putrescine, spermidine, histamine, tyramine and some amino
      acids precursors, histidine and tyrosine, in food products, based on ion-exchange
      chromatography (IC) with integrated pulsed amperometric detection (IPAD) has been
      developed. The method was successfully used for the analysis of biogenic amines
      and amino acids in food both of vegetable (kiwi, Actinidia chinensis) and animal
      origin, (fish, pilchard), as well as in fermented foods, such as cheese
      (Emmenthal) and dry sausages (salami). The method was also successfully used to
      study the changes in biogenic amines during the ripening of dry fermented
      sausages (salami). The analytes were extracted from foods with perchloric acid
      and the extracts were purified by liquid-liquid partition using n-hexane.
      Determination of biogenic amines was performed through cation-exchange
      chromatography with isocratic elution and IPAD. The detection limits for the
      analytes under investigation were found to range from 1.25 to 2.50 ng, at a
      signal-to-noise ratio of 3:1. Average recoveries ranged from 85.5 to 97.4% and
      R.S.D. values ranged from 3.4 to 8.8. The proposed method offers a number of
      advantages over our previous IPAD method, such as the application to a larger
      number of analytes and matrices, a simpler extraction procedure and clean-up,
      isocratic elution using low acid and base concentrations, an improved
      chromatographic separation and a lower detection limit.

PMID- 9542133
TI  - High-performance liquid chromatographic peak identification of 2,4
      dinitrophenylhydrazine derivatives of lipid peroxidation aldehydes by photodiode
      array detection.
AB  - Malonaldehyde (MDA), a product of lipid peroxidation, is a presumptive marker for
      the development of oxidative stress in tissues and plasmas. In this study we
      report the photodiode array detection of the 2,4-dinitrophenylhydrazine (DNPH)
      derivatives of MDA using HPLC. Oxidative stress was produced by injecting (i.p.)
      bacterial lipopolysaccharide (LPS) into rats at a dose of 100 micrograms/kg, or
      i.v. into rabbits (1 microgram/kg), or added to freshly drawn human blood (200
      ng/ml). Blood was collected at several time points up to 5 h, centrifuged, and
      equal volumes of 20% TCA were used to precipitate proteins from the plasma. The
      supernatants were derivatized with DNPH, and the aldehyde-DNPHs were extracted
      with pentane. After evaporation, aliquots of 10 microliters in acetonitrile were
      injected onto a Beckman Ultrasphere C18 (3 microns) column, chromatographed with
      an acetonitrile-water-acetic acid gradient mobile phase and scanned using Waters
      996 photodiode array detector. Peak identification and homogeneity was determined
      by comparing the experimental peaks and UV scans with those of authentic
      standards. A significant increase in the DNPH derivative of malonaldehyde (MDA
      DNPH), but not of the other aldehyde-DNPH derivatives of formaldehyde (FDA),
      acetaldehyde (ADA), acetone and propionaldehyde (PDA) was seen over the first
      hour after LPS administration in anesthetized rats, while in conscious rabbits
      this trend lasted up to 3 h. The retention times as well as the UV scans of the
      derivatized aldehydes matched the authentic standards. Thus, photodiode array
      detection has proved valuable in establishing this HPLC method for estimating
      oxidative stress. This technique could accurately measure pmol amounts of MDA
      DNPH indicating the usefulness of photodiode array detection method for
      estimating small changes in the oxidative stress.

PMID- 9542134
TI  - Rapid determination of vitamins A and E in serum with surfactant as a diluent by
      column-switching high-performance liquid chromatography.
AB  - The rapid and simple determination of fatty vitamins (vitamins A and E) in serum
      by high-performance liquid chromatography with a column-switching technique was
      investigated. The dilution of serum with an aqueous solution containing
      surfactant and organic solvent and the use of an aqueous solution with organic
      solvent as a sample pretreatment were an effective means of improving the sample
      recovery. To prevent sample decomposition during storage, the addition of an
      antioxidant reagent into the diluent was required. Under the optimal conditions,
      the relative standard deviation (R.S.D.) values against the standard samples were
      1.12% (16.7 I.U./dl), 0.25% (333 I.U./dl) for vitamin A, and 1.02% (0.43
      microgram/ml), 0.45% (8.5 micrograms/ml) for vitamin E, respectively. The
      relative coefficients (r2) between the sample amounts in serum and the peak areas
      were 1.0000 in the range from 16.7 to 667 I.U./dl (for vitamin A) and 0.9998 from
      0.434 to 17.46 micrograms/ml (for vitamin E). The recoveries of vitamins from
      spiked serums were ca. 100% (vitamin A) and ca. 86% (vitamin E), respectively. By
      the combination of an on-line deproteination column and diluting solution, the
      simple and rapid determination of fatty vitamins could be routinely achieved in
      18-min intervals.

PMID- 9542135
TI  - Isolation of a new okadaic acid analogue from phytoplankton implicated in
      diarrhetic shellfish poisoning.
AB  - A new analogue of okadaic acid (OA), the toxin mainly responsible for diarrhetic
      shellfish-poisoning (DSP) phenomena in Europe, has been isolated from toxic
      phytoplankton (Dinophysis acuta) collected in Irish waters. Fluorimetric LC
      analyses of the extracts of bulk phytoplankton samples using derivatisation with
      9-anthryldiazomethane (ADAM) showed a complex toxin profile, with peaks
      corresponding to OA and dinophysistoxin-2 (DTX-2) as well as a third unidentified
      compound. This minor unidentified component was isolated by chromatographic
      techniques such as normal-phase chromatography, gel permeation on Sephadex, solid
      phase extraction and reversed-phase separations. Ionspray mass spectrometry (MS)
      was used for structural investigation on this compound due to the very small
      amount of isolated material. Flow injection analysis (FIA)-MS of the isolated
      compound gave positive-ion mass spectrum dominated by the protonated molecule, [M
      + H]+, at signal m/z 805, whereas the deprotonated molecule [M - H]- was observed
      in the negative-ion spectrum at signal m/z 803, thus indicating the molecular
      weight of 804 for the new toxin, the same as OA and its known isomers, DTX-2 and
      DTX-2B. Collision-induced dissociation (CID) as obtained by positive and negative
      tandem mass spectrometry (MS-MS) showed a fragmentation pattern for the new
      compound which was very similar to that of OA, DTX-2 and DTX-2B. Ionspray microLC
      MS of a mixture containing the compound under investigation together with OA
      analogues showed the compound eluted after OA, DTX-2, DTX-2B and before DTX-1.
      All the chromatographic and mass spectrometric data indicated the compound to be
      another OA isomer and it was therefore coded DTX-2C. To the best of our knowledge
      this is the first report on the isolation of a new compound related to DSP toxins
      from natural communities of toxic phytoplankton.

PMID- 9542136
TI  - Sensitive determination of anatoxin-a, homoanatoxin-a and their degradation
      products by liquid chromatography with fluorimetric detection.
AB  - Cyanobacterial neurotoxins have been implicated in animal deaths resulting from
      drinking contaminated water. Anatoxin-a (AN) and homoanatoxin-a (HMAN) have
      previously been analysed using high-performance liquid chromatography (HPLC) with
      UV detection, but this procedure is insufficiently sensitive and is subject to
      interferences. A sensitive fluorimetric (FL) method for determining AN was
      recently developed using derivatisation with 4-fluoro-7-nitro-2,1,3
      benzoxadiazole (NBD-F) and this has been applied to the simultaneous
      determination of AN, HMAN and their epoxy and dihydro degradation products.
      Microscale syntheses were used to prepare the dihydro and epoxy derivatives from
      AN and HMAN. These compounds were produced in high yields, as confirmed by
      electrospray MS and HPLC-FL of their benzoxadiazole derivatives. All six NBD
      derivatives were readily separated using isocratic reversed-phase HPLC. The
      recoveries of these compounds from spiked water samples, using weak cation
      exchange (WCX) solid-phase extraction (SPE), were 83.2-84.9% at concentrations of
      10 micrograms/l. The R.S.D. values were 1.7-3.9% (n = 8) and the limits of
      detection were better than 10 ng/l for all six compounds, illustrating the high
      sensitivity of the method. This methodology was successfully applied to the
      analysis toxin degradation products in natural samples. Dihydroanatoxin-a (0.8
      mg/g) was isolated from a benthic Oscillatoria bloom from Caragh Lake, Ireland,
      and was found to contain two isomers but their ratio was different from that
      found in the synthetic material.

PMID- 9542138
TI  - Liquid chromatographic determination of beta-naphthoxyacetic acid in tomatoes.
AB  - An alternative high-performance liquid chromatographic method for the
      determination of beta-naphthoxyacetic acid (BNOA) in tomatoes is described. BNOA
      was extracted from tomatoes with acetone-dichloromethane (2:1). The extract was
      cleaned up by Bio-Beads S-X3 gel-permeation chromatography and by partitioning. A
      reversed-phase C18 column was used for HPLC analysis. The mobile phase was
      acetonitrile-2% acetic acid in water (50:50, v/v) pumped at a flow-rate of 1.0
      ml/min. Retention time of BNOA was ca. 7 min with a percentage coefficient of
      variation of 0.71. Resolution of BNOA was good on the column. Percentage
      recoveries of BNOA were 79.5 +/- 6.82, 94.8 +/- 2.70 and 86.4 +/- 16.43 for the
      corresponding spiking levels of 0.5, 1.0 and 2.0 micrograms per g tomato,
      respectively. Analysis of 10 greenhouse tomato samples from local markets in
      Ankara showed no BNOA residue.

PMID- 9542137
TI  - Automated on-line solid-phase extraction and high-performance liquid
      chromatographic analysis of total and free pyridinium crosslinks in serum.
AB  - An automated on-line solid-phase extraction procedure for free and total
      pyridinium crosslinks in serum, with HPLC analysis, is described. The pyridinium
      crosslinks either following hydrolysis in 3 M HCl or free in neat serum were
      extracted using a Gilson Aspec XLi system onto extraction cartridges containing
      an octylsilane/cation exchanger sorbent. Up to 525 microliters of serum could be
      loaded onto the extraction cartridges. After washing, the crosslinks were eluted
      with 400 microliters of 100 mM sodium formate pH 5 and 380 microliters of this
      was concentrated on a RPB guard column eluted with 100 mM HFBA. The crosslinks
      were backflushed and separated on a 5-micron ODS analytical column eluted with 30
      mM HFBA with 18% MeCN at 1 ml/min and detected by their native fluorescence
      (excitation 295 nm, emission 400 nm). The use of a high sensitivity fluorescence
      detector was essential. Recoveries were 95-100% with a limit of detection (S/N =
      2) of 109 pmol/l (pM) for pyridinoline (Pyr) and 143 pM for deoxypyridinoline
      (dPyr). The inter-assay R.S.D. was 9% for pyridinoline and 10.8% for
      deoxypyridinoline. The throughput of the system was up to 50 samples per day.

PMID- 9542139
TI  - High-performance liquid chromatographic assay of 8-hydroxyquinoline sulfate and
      its stability in immunobiological preparations.
AB  - Because of the ability of 8-hydroxyquinoline sulfate (8-HQS) to irreversibly bind
      metals from rubber stoppers, the stability of 8-HQS in tuberculin solutions was
      investigated. For the determination of 8-HQS, a simple and sensitive reversed
      phase HPLC method with detection at 240 nm was developed and validated. Rapid
      decreases in concentrations of 8-HQS were found in samples stored in original
      vials which were exposed to different temperatures and vial positions.

PMID- 9542141
TI  - Optimisation, validation and application of a capillary electrophoresis method
      for the determination of ranitidine hydrochloride and related substances.
AB  - Ranitidine hydrochloride is an H2-antagonist which is widely prescribed for the
      treatment of peptic ulcers. The drug is marketed in a variety of dosage forms
      including tablets, syrups and injection solutions. A range of synthetic and
      degradative impurities of ranitidine are known and currently, these impurities
      are routinely determined using thin-layer chromatography (TLC). Alternatively a
      high-performance liquid chromatography (HPLC) method has also been employed in
      the assay of the pharmaceutical preparation. Unlike TLC, capillary
      electrophoresis (CE) offers the capability to quantify simultaneously both the
      active drug content and the levels of the related substances. The advantages of
      simplicity, selectivity, versatility and ease of use of CE offers a complementary
      separation technique to the established methods of HPLC and TLC in the
      determination of ranitidine and its related substances. This work represents a
      comprehensive evaluation of the performance of a developed CE method in the
      determination of drug-related impurities in both drug substance and various
      pharmaceutical formulations. The data obtained clearly shows that the performance
      of an optimised CE method can be equivalent in terms of sensitivity and precision
      to that of a HPLC method employed for a similar purpose and offers better
      selectivity against TLC and HPLC.

PMID- 9542140
TI  - Capillary electrochromatography of steroids increased sensitivity by on-line
      concentration and comparison with high-performance liquid chromatography.
AB  - A reversed-phase HPLC method previously developed for the analysis of
      progesterone and its major metabolites has been transferred successfully to a
      capillary electrochromatography (CEC) system. Procedures for fabricating packed
      capillaries and the modifications made to the capillary electropherograph which
      allow operation in the CEC mode without pressurisation are described. The
      dependence of electroosmotic flow on electric field strength, pH and organic
      modifier content is discussed. Direct comparison with HPLC shows that CEC
      provides useful gains in efficiency and speed of analysis and requires vastly
      reduced amounts of both chromatographic phases and material for analysis. On-line
      concentration is described which allows the lower sensitivity of CEC to be offset
      by injecting analytes from a non-eluting solution. Examination of steroids in
      plasma demonstrates that the superior separation by CEC is maintained in a
      complex biological matrix.

PMID- 9542142
TI  - Separation of ibuprofen, codeine phosphate, their degradation products and
      impurities by capillary electrophoresis. I. Method development and optimization
      with fractional factorial design.
AB  - A capillary electrophoresis method has been developed and optimized for the
      separation of ibuprofen, codeine phosphate and their main degradation products
      and impurities. In the course of developing the method, it was found that
      micellar electrokinetic capillary chromatography was necessary for the separation
      of the eleven peaks. A fractional factorial design was used for the optimization
      of the experiments. Six process parameters were varied at two levels: the
      concentration of sodium dodecyl sulfate (SDS), the pH, the concentration of
      acetonitrile, the concentration of boric acid, the field strength and the
      temperature. All these factors had a significant effect on the migration time and
      resolution. The optimum conditions were found to be a borate buffer of 40 mM
      H3BO3 at pH 10 with the addition of 40 mM SDS and 9% acetonitrile, a field
      strength of 515 V/cm and a temperature of 25 degrees C. This resulted in baseline
      separation of the eleven peaks within 12 min.

PMID- 9542143
TI  - Determination of methamphetamine and related compounds by capillary
      electrophoresis with UV and laser-induced fluorescence detection.
AB  - Methods for the simultaneous determination of methamphetamine (MP) and its
      related compounds (MPs) using capillary electrophoresis (CE) with UV absorbance
      and laser-induced fluorescence (LIF) detection are described. In UV detection,
      MPs were applied to CE without any derivatization procedure and detected at 210
      nm for a rapid and simple analysis. Capillary zone electrophoresis (CZE) and
      electrokinetic capillary electrophoresis (MEKC) were used. MP, amphetamine (AP),
      1-phenylethylamine (1-PA as an I.S.), 2-phenylethylamine (2-PA), 4
      hydroxymethamphetamine (4-HMP) and 4-hydroxyamphetamine (4-HAP) were separated
      within 15 min by both CZE and MEKC. Detection limits of MPs were in the range 48
      72 fmol/injection for CZE and 85-191 fmol/injection for MEKC. MEKC was
      successfully applied to the determination of MPs in urine. For a highly sensitive
      analysis, LIF detection was also examined using 4-fluoro-7-nitro-2,1,3
      benzoxadiazole (NBD-F) as a fluorescent derivatization reagent. By the method, in
      which MPs derivatives were separated within 45 min by MEKC, 22-40 amol/injection
      of primary amines (AP, 4-HAP and 2-PA) and 690 amol/injection of MP and 300
      amol/injection of 4-HMP were detected. The concentration of MP and AP in 50
      microliters urine from MP addicts were successfully determined. A comparison of
      the characteristics for both UV and LIF detections was also discussed.

PMID- 9542144
TI  - Determination of antibacterial quaternary ammonium compounds in lozenges by
      capillary electrophoresis.
AB  - A method for the specific determination of three quaternary ammonium compounds,
      benzalkonium chloride, cetylpyridinium chloride and dequalinium chloride, used as
      antibacterial agents in candy-based lozenges, is described based on capillary
      zone electrophoresis. It is shown that, following optimisation of buffer
      composition with respect to organic modifier concentration. pH and buffer
      concentration together with the inclusion of sodium dodecylsulphate as an ion
      pairing agent in the case of dequalinium chloride, these analytes migrate in less
      than 5 min. The resultant electrophoretic peaks are sharp and readily quantified.
      The individual alkyl components of benzalkonium chloride can be resolved as can
      related impurities in dequalinium chloride lozenges. The quantitative
      characteristics of the assay method, based on peak areas normalised with respect
      to migration times, are reported and the method is compared with a previously
      published method based on liquid chromatography.

PMID- 9542145
TI  - Thermogenic responses to body cooling during fever induced by Staphylococcus
      aureus cell walls in rabbits.
AB  - Hypothalamic temperature (Thypo) and metabolic heat production (M) were measured
      in seven conscious rabbits injected intravenously with either saline or with
      Staphylococcus aureus, (8.10(7) cell walls.kg-1) while being subjected to a 3-h
      period of ramp-like total body cooling using a chronically implanted
      intravascular heat exchanger. In pyrogen-injected animals cooling started (1) at
      the time of injection or (2) 70 min after injection. In (1) the fall in Thypo
      induced by heat extraction was similar (1.0 degree C) in afebrile and febrile
      animals. In (2) there was a transient increase in Thypo of about 0.5 degree C at
      a time corresponding to the start of fever resulting in a significantly smaller
      fall in Thypo at the end of the 3-h cooling period (0.5 degree C vs 0.9 degree C,
      P < 0.05, n = 5). At this time in both (1) and (2) M was lower than theoretically
      expected from the increase in shivering threshold during fever. However, most of
      this effect can be explained when available data showing a decrease in
      thermosensitivity during S. aureus-induced fever are taken into account. After
      cessation of cooling in both groups of febrile animals Thypo rose to about 1
      degree C higher than the precooling level, which is comparable to the fever level
      in a separate series of experiments with S. aureus injection without cooling (1.2
      degrees C).

PMID- 9542146
TI  - Effects of vertebrate growth factors on digestive gland cells from the mollusc
      Pecten maximus L.: an in vitro study.
AB  - In relation with the digestive cycle, the digestive gland cells of bivalve
      molluscs undergo a sequence of cytological changes which is controlled by
      external and internal effectors such as putative gastrointestinal hormones and
      growth differentiation factors. A tissue dissociation method was developed to
      investigate the in vitro effect of the vertebrate growth and differentiation
      factors: insulin, insulin growth factor I (IGF-I), basic fibroblast growth factor
      (bFGF) and epidermal growth factor (EGF) on the digestive gland cells of the
      scallop Pecten maximus. All these vertebrate peptides induced a dose-dependent
      increased incorporation of 3H-leucine and 14C-uridine in whole digestive gland
      cell suspensions. However, after Percoll density gradient purification of the
      digestive cells, only stem and undifferentiated enriched cell fractions were
      responsive to the different peptides. In addition, insulin and IGF-I, but not EGF
      and bFGF, stimulated 3H-leucine incorporation in control dispersed mantle edge
      cells. These results suggest that insulin-related peptides could work as general
      growth promoting factors in molluscs. On the other hand, EGF and bFGF, or at
      least their molluscan counterparts, may be efficient growth differentiation
      factors in the regenerative processes occurring in the digestive gland of
      molluscs.

PMID- 9542147
TI  - The energy cost of flight: do small bats fly more cheaply than birds?
AB  - Flapping flight is one of the most expensive activities in terms of metabolic
      cost and this cost has previously been considered equal for the two extant
      vertebrate groups which evolved flapping flight. Owing to the difficulty of
      obtaining accurate measurements without disturbing flight performance, current
      estimates of flight cost within the group of small birds and bats differ by more
      than a factor of five for given body masses. To minimize the potential problem
      that flight behaviour may be affected by the measurements, we developed an
      indirect method of measuring flight energy expenditure based on time budget
      analysis in which small nectar-feeding bats (Glossophaginae) could continue their
      natural rhythm of flying and resting entirely undisturbed. Estimates of metabolic
      flight power based on 172 24-h time and energy budget measurements were obtained
      for nine individual bats from six species (mass 7-28 g). Metabolic flight power
      (PF) of small bats was found to increase with body mass following the relation PF
      = 50.2 M0.771 (r2 = 0.96, n = 13, PF in W, M in kg). This is about 20-25% below
      the majority of current predictions of metabolic flight cost for small birds.
      Thus, either the flight cost of small birds is significantly lower than has
      previously been thought or, contrary to current opinion, small bats require less
      energy to fly than birds.

PMID- 9542148
TI  - Antioxidant defenses and lipid peroxidation damage in estivating toads,
      Scaphiopus couchii.
AB  - Tissue-specific changes in antioxidant defenses and lipid peroxidation damage
      were analyzed in spadefoot toads, Scaphiopus couchii, to determine how these
      responded during estivation, a state of suppressed oxygen consumption. Maximal
      activities of glutathione-S-transferase, glutathione reductase, glutathione
      peroxidase, superoxide dismutase and catalase were measured in six organs from 2
      month-estivated toads and compared with activities in animals awakened for 10
      days after estivation. Activities of many enzymes, particularly the glutathione
      linked enzymes, were significantly lower in tissues of estivating toads than in
      awake toads. This indicates that enzymatic antioxidant defenses are probably
      modulated in response to the rate of reactive oxygen species generation in
      tissues, which is proportional to oxygen consumption. Antioxidant enzyme
      activities were largely insensitive to high urea, which accumulates during
      estivation, but were inhibited by elevated KCl. Levels of reduced glutathione
      were also significantly lower in three organs during estivation and all organs,
      except skeletal muscle, exhibited a higher oxidized/reduced glutathione ratio,
      indicating a more oxidized state during estivation. Products of lipid
      peroxidation (conjugated dienes, lipid hydroperoxides) were higher in tissues of
      estivated than control toads, suggesting accumulated oxidative damage to lipids
      during dormancy. One enzymatic source of free radical generation, xanthine
      oxidase, appeared to have little impact because its activity was detectable only
      in liver and was significantly lower in estivated toads. The data indicate that
      both enzymatic and metabolite antioxidant defenses in toads are adaptable systems
      that are modulated in estivating versus awake states.

PMID- 9542149
TI  - Energy metabolism of underwater swimming in river-otters (Lutra lutra L.).
AB  - We used a still-water swim channel in conjunction with open-flow oxygen and
      carbon dioxide respirometry to examine the energy requirements of river-otters
      (Lutra lutra L.) swimming voluntarily underwater in Neumunster Zoo (Germany).
      While at rest on land (5 degrees C), river-otters had a respiratory quotient of
      0.77 and a resting metabolic rate of 4.1 W kg-1. This increased to an estimated
      6.4 W kg-1 during rest in water (11-15 degrees C) and to 12.3 W kg-1 when the
      animals were feeding in the channel. River-otters swimming under water preferred
      a mean speed of 0.89 m s-1, and their energy requirements attained 11.6 W kg-1.
      Cost of transport, however, was minimal at 1.3 m s-1 and amounted to 0.95 J N-1 m
      1.

PMID- 9542151
TI  - Non-myotendinous force transmission in rat extensor digitorum longus muscle.
AB  - The extensor digitorum longus muscle (EDL) of the rat hindleg consists of four
      heads. The heads are named after their insertions on the digits of toes II, III,
      IV and V. The EDL heads share a proximal tendon and aponeurosis, but have
      separate distal aponeuroses and tendons. By cutting the distal tendons of
      selected heads, direct myotendinous force transmission within these heads is
      prevented. Therefore, force exerted by the muscle would be expected to decrease
      according to the physiological cross-sectional area disconnected if myotendinous
      force transmission were the only mechanism of force transmission. The results
      indicate that EDL force production remained at high levels after acute tenotomy:
      muscle length-force curves did not alter significantly following cutting of the
      tendons of heads II and III. Cutting the tendon of head IV as well leaves only
      head V in its original condition. After tenotomy of head IV, length-force
      characteristics were altered significantly, but optimum force was maintained at
      84% of that of the intact muscle. After separation of head IV from head V
      intramuscularly for some distance along their interface, the force dropped to
      much lower levels, with optimum force approaching 50% of that of the intact
      muscle. The length of active proximal fibres (located within head II) did not
      remain constant but increased with increasing muscle lengths after tenotomy as
      well as after partial separation of heads IV and V. The amount of length change
      decreased after intramuscular separation of the heads, indicating declining
      reactive forces. It is concluded that force transmission occurred from
      tenotomized heads to their intact neighbours and vice versa. The magnitude of the
      force transmitted from head to head was dependent on the degree of integrity of
      the connective tissue at the interface between heads.

PMID- 9542152
TI  - Chloride transport in red blood cells of lamprey Lampetra fluviatilis: evidence
      for a novel anion-exchange system.
AB  - The existence of a furosemide-sensitive Cl- transport pathway activated by
      external Ca2+ and Mg2+ has been demonstrated previously in studies of Cl- influx
      across the lamprey erythrocyte membrane. The aim of the present study was to
      characterize further specific Cl- transport pathways, especially those involved
      in Cl- efflux, in the red blood cell membrane of Lampetra fluviatilis. Cl- efflux
      was inhibited by 0.05 mmol l-1 dihydroindenyloxyalkanoic acid (DIOA) (81%), 1
      mmol l-1 furosemide (76%) and 0.1 mmol l-1 niflumic acid (54%). Bumetanide (100
      mumol l-1) and DIDS (100 mumol l-1) had no effect effect on Cl- efflux.
      Substitution of external Cl- by gluconate, but not by NO3-, led to a gradual
      decline of Cl- efflux. In addition, the removal of external Ca2+ resulted in a
      significant reduction in the rate of Cl- efflux. Membrane depolarization caused
      by increasing external K+ concentration or by inhibiting K+ channels with 1 mmol
      l-1 Ba2+ did not affect Cl- efflux. The furosemide-sensitive component of Cl-
      influx was a saturable function of external [Cl-] with an apparent K(m) of
      approximately 92 mmol l-1 and Vmax of approximately 17.8 mmol l-1 cells-1 h-1.
      Furosemide did not affect intracellular Cl- concentration (57.6 +/- 5.2 mmol l-1
      cell water), measured using an ion-selective Cl- electrode, showing that a
      furosemide-sensitive pathway is not involved in net Cl- movement. A gradual fall
      (from 28.1 +/- 1.4 to 15.0 +/- 1.3 mmol l-1 cells-1 h-1) in unidirectional Cl-
      influx with time was observed within 3 h of cell preincubation in the standard
      physiological medium. These data provide evidence for the existence for an
      electroneutral furosemide-sensitive anion-exchange pathway in the lamprey
      erythrocyte membrane that accepts chloride and nitrate, but not bicarbonate or
      bromide.

PMID- 9542153
TI  - Characterization of Na+ and Ca2+ currents in bag cells of sexually immature
      Aplysia californica.
AB  - The neurosecretory bag cells of sexually mature Aplysia californica release egg
      laying hormones as part of the reproductive process after a train of action
      potentials termed afterdischarge. Whole-cell voltage-clamp experiments were
      performed in cultured cells from sexually immature A. californica to characterize
      the inward voltage-gated currents for Na+ and Ca2+. The goal of these experiments
      was to investigate the regulation of excitability during sexual maturation. Na+
      currents in bag cells of immature A. californica were similar in several ways to
      those of mature animals. The Na+ currents activated at voltages less negative
      than -30 mV and peaked at 10-20 mV in artificial sea water. The time course and
      pharmacology of bag cell Na+ currents were similar to those of bag cells from
      mature A. californica, although the Na+ current density was lower in immature A.
      californica. Na+ currents were inhibited by tetrodotoxin (50 nmol l-1). The Na+
      current was relatively insensitive to depolarized holding potentials (Vh),
      maintaining approximately 50% of peak current amplitude present at Vh = -70 mV
      throughout the activation range at Vh = -30 mV. In experiments using a 1 s
      depolarized Vh prior to a test pulse, the half-inactivation voltage (V1/2) was 
      27 mV. Recovery of immature Na+ current from steady-state inactivation at Vh = 
      30 mV had a time constant (tau) of 9.5 ms, significantly slower than in mature
      animals. Ca2+ currents of immature A. californica activated at approximately -30
      mV and peaked at approximately 20 mV with 11 mmol l-1 Ba2+ as the charge carrier.
      The principle differences from mature Ca2+ currents were the low density of the
      immature Ca2+ currents and their 'run-down' in whole-cell recordings. The
      pharmacology and V1/2 of bag cell Ca2+ currents were similar to those of L-type
      Ca2+ currents in mature cells. The Ca2+ currents were inhibited 61 +/- 10% by
      nifedipine (10 mumol l-1) and were unaffected by omega-conotoxin GVIA (10 mumol l
      1). The Ca2+ currents were relatively insensitive to depolarized Vh, activating
      maximally at Vh = -90, -70 and -50 mV, and maintaining 50% of this peak current
      amplitude throughout the activation range at Vh = -30 mV. The V1/2 was -23 mV in
      experiments in which cells were subjected to a 1 s depolarized Vh prior to a test
      pulse. Na+ current amplitudes were maintained or increased during 1 min of 4 Hz
      test pulses in bag cells at Vh = -70 mV and Vh = -30 mV. In contrast, Ca2+
      current run-down occurred during 1 min of 4 Hz test pulses in seven of 10 cells
      at Vh = -70 mV and in 12 of 12 cells at Vh = -30 mV. The observed scarcity of Na+
      and Ca2+ currents in immature bag cells as well as the specific characteristics
      of immature bag cell Ca2+ currents make repetitive action potential firing and
      hormone release less likely than in mature bag cells.

PMID- 9542154
TI  - Seasonal changes in the cardiovascular, respiratory and metabolic responses to
      temperature and hypoxia in the bullfrog Rana catesbeiana.
AB  - We assessed seasonal variations in the effects of temperature on hypoxia-induced
      alterations in the bullfrog Rana catesbeiana by measuring the heart rate,
      arterial blood pressure, breathing frequency, metabolic rate, blood gas levels,
      acid-base status and plasma glucose concentration. Regardless of the season,
      decreased body temperature was accompanied by a reduction in heart and breathing
      frequencies. Lower temperatures caused a significant decrease in arterial blood
      pressure during all four seasons. Hypoxia-induced changes in breathing frequency
      were proportional to body temperature and were more pronounced during winter,
      less so during spring and autumn and even smaller during summer. Season had no
      effect on the relationship between hypoxia and heart rate. At any temperature
      tested, the rate of oxygen consumption had a tendency to be highest during summer
      and lowest during winter, but the difference was significant only at 35 degrees
      C. The PaO2 and pH values showed no significant change during the year, but PaCO2
      was almost twice as high during winter than in summer and spring, indicating
      increased plasma bicarbonate levels. Lower temperatures were accompanied by
      decreased plasma glucose levels, and this effect was greater during summer and
      smaller during autumn. Hypoxia-induced hyperglycaemia was influenced by
      temperature and season. During autumn and winter, plasma glucose level remained
      elevated regardless of temperature, probably to avoid dehydration and/or
      freezing. In winter, the bullfrog may be exposed not only to low temperatures but
      also to hypoxia. These animals show temperature-dependent responses that may be
      beneficial since at low body temperatures the set-points of most physiological
      responses to hypoxia are reduced, regardless of the season.

PMID- 9542155
TI  - alpha-Glucosidase from the hepatopancreas of the shrimp, Penaeus vannamei
      (Crustacea-Decapoda).
AB  - Penaeus vannamei is an omnivorous species, and it can be assumed that a high
      level of carbohydrates is necessary for growth. Alpha-glucosidases are important
      enzymes necessary for the ultimate liberation of glucose residues from various
      carbohydrates. Using acarbose affinity chromatography, a glycosylated alpha
      glucosidase with a molecular mass of approximately 105 kDa was isolated for the
      first time from the hepatopancreas of the shrimp. Exhibiting an optimal catalytic
      activity in the temperature range from 40 degrees C to 50 degrees C at pH 6, the
      purified enzyme hydrolyses alpha 1-4 bonds and liberates glucose from different
      oligo and polysaccharides. By contrast to other known glucosidases, no alpha 1-6
      glucose link with hydrolysis has been observed. This could explain the different
      rates of growth in shrimp aquaculture with starches from various origins. The
      amino-acid composition, together with the partial sequence of a hydrolytic
      peptide, shows a high degree of similarity to the alpha-glucosidases reported for
      various organisms including yeast and fungi and may help determine the phylogeny
      of the family.

PMID- 9542156
TI  - Transfer of steroidal and nonsteroidal compounds across guinea pig fetal
      membranes.
AB  - Transfer of steroidal and nonsteroidal compounds across guinea pig amnion and
      chorion laeve was investigated as a function of stage of gestation, tissue
      orientation, steroid specificity, and molecular size. Each fetal membrane was
      examined at early and late stages of gestation, before and after pubic symphysis
      relaxation. Early amnion was impermeable to macromolecules and small charged
      molecules while [3H]estrone and [3H]pregnenolone were transferred, the latter
      depending on tissue orientation and involving conjugation at the basolateral
      interface. After symphysis dilation, amnion transferred all substrates tested
      with the exception of BSA; the molecular weight cutoff was approximately 5,000.
      Unlike amnion, early chorion transferred both free and conjugated steroids as
      well as inorganic sulfate. Transfer of estrone involved conjugation and depended
      on tissue orientation. Transfer of [3H]estrone-sulfate, [3H]estrone-glucuronide,
      and [3H]pregnenolone-sulfate was similar despite selective deconjugating activity
      toward estrone-sulfate. Near term, chorion was impermeable to inorganic sulfate
      and transfer of estrone-glucuronide depended on tissue orientation, involving
      deconjugation in the maternal to fetal direction. At no stage of gestation did
      chorion transfer macromolecules. These results suggest that the transfer of free
      and conjugated steroids across fetal membranes is differentially regulated by
      tissue, its stage of development, and direction of transfer.

PMID- 9542157
TI  - Lymphocyte proliferative response in brown bears: cytokine role and
      glucocorticoid effect.
AB  - Lymphocyte stimulation and proliferation play a pivotal role in the immune
      response to soluble as well as to cellular, bacterial, and viral antigens. In
      this study, peripheral blood mononuclear cells (PBMC), mainly composed of
      lymphocytes, were separated by Ficoll-Hypaque density gradient centrifugation
      from 50-ml jugular vein blood samples drawn from six captive and five wild-caught
      brown bears (Ursus arctos) (eight Apennine brown bears from the Italian
      population; three of undetermined origin). Stimulation of cultured bear PBMC with
      the two classical T lymphocyte mitogens phytohemagglutinin (PHA) and Concanavalin
      A (ConA) was followed by a significantly greater proliferative response than that
      shown by human PBMC (n = 11) (PHA: T = 4.03, d.f. = 20, P = 0.001; ConA: T =
      4.25, d.f. = 20, P < 0.0005; Student's t-test, oneway ANOVA). As in humans, the
      PBMC proliferative response in bears was markedly (> 50%) inhibited by addition
      of transforming growth factor beta (TGF beta) human recombinant cytokine to the
      culture. Further fractionation provided a cell preparation extremely rich in
      peripheral blood lymphocytes (PBL) (mean +/- SD = 96.1 +/- 1.7%). Addition of
      interleukin 1 (IL1) or interleukin 2 (IL2) human recombinant cytokines to
      cultured PBL stimulated with a suboptimal concentration of mitogens resulted in a
      ninefold increase in the lymphocyte proliferative response. Dexamethasone (DEX, a
      synthetic analog of hydrocortisone) inhibited the bear PBMC proliferative
      response by 22.2 +/- 4.3% (mean +/- SD), compared with 46.2 +/- 6.9% and 91.8 +/-
      8.1% (mean +/- SD) in humans and mice (n = 11) (Mus domesticus), respectively.
      Inhibition of the brown bear and human PBMC responses was markedly (> 60%)
      reduced by the addition of IL2. The finding that IL1 and IL2 augment and that DEX
      inhibits bear lymphocyte proliferative response suggests that these cytokines can
      be used to increase the immune response in vaccinations, and that DEX may hamper
      several immunologically mediated diseases.

PMID- 9542159
TI  - Low genetic variation among killer whales (Orcinus orca) in the eastern north
      Pacific and genetic differentiation between foraging specialists.
AB  - Killer whales from the coastal waters off California through Alaska were compared
      for genetic variation at three nuclear DNA markers and sequenced for a total of
      520 bp from the mitochondrial control region. Two putative sympatric populations
      that range throughout this region were compared. They can be distinguished by
      social and foraging behavior and are known as "residents" and "transients". We
      found low levels of variation within populations compared to other cetacean
      species. Comparisons between fish (resident) versus marine mammal (transient)
      foraging specialists indicated highly significant genetic differentiation at both
      nuclear and mitochondrial loci. This differentiation is at a level consistent
      with intraspecific variation. A comparison between two parapatric resident
      populations showed a small but fixed mtDNA haplotype difference. Together these
      data suggest low levels of genetic dispersal between foraging specialists and a
      pattern of genetic differentiation consistent with matrifocal population
      structure and small effective population size.

PMID- 9542158
TI  - Analysis of mitochondrial DNA indicates that domestic sheep are derived from two
      different ancestral maternal sources: no evidence for contributions from urial
      and argali sheep.
AB  - To investigate the origins and phylogenetic relationships of domestic sheep,
      mitochondrial DNA (mtDNA) from 243 sheep of five European, one African, and four
      Asian breeds and several mouflon (Ovis musimon), urial (O. vignei bochariensis),
      and argali (O. ammon nigrimontana, O. a. collium) were assayed for restriction
      fragment length polymorphisms (RFLP). Twenty haplotypes were identified which
      occurred in three major phlogenetic groups: urial/argali, mouflon/domestic, and
      domestic sheep. From the branches that contain mouflon and domestic sheep, two
      major domestic sheep lineages are apparent. One lineage, termed European lineage,
      contains the majority of haplotypes detected among European domestic sheep. These
      mtDNAs resemble mouflon haplotypes. The other lineage, termed Asian lineage,
      consists of haplotypes found in central Asian and some European domestic sheep.
      The mean sequence difference between these two lineages (0.72%) is of similar
      magnitude as that between two argali subspecies. To accurately estimate sequence
      differences between the European and Asian mtDNA types, the mitochondrial control
      region of one animal from each lineage and of one mouflon and urial were
      completely sequenced. Sequence comparisons show that Asian and European domestic
      sheep lineages differ by 4.43%. The mouflon sequences diverges from the Asian
      type by 4.52%, but by only 1.36% from the European type. Our data supports the
      hypothesis that some modern domestic sheep and European mouflon derive from a
      common ancestor and provide evidence of an additional wild ancestor, other than
      the urial and argali groups, which has yet to be identified.

PMID- 9542160
TI  - Mitochondrial DNA variability in Grauer's gorillas of Kahuzi-Biega National Park.
AB  - Eastern lowland gorillas (Gorilla gorilla graueri) are the least studied of the
      three gorilla subspecies; particularly at the molecular level. We sequenced an
      internal region of the mitochondrial DNA cytochrome oxidase subunit II (COII)
      region and a hypervariable portion of the mitochondrial DNA control region (D
      loop) from wild gorillas in both the montane and lowland habitats of Kahuzl-Blega
      National Park, Democratic Republic of Congo. All individuals (n = 38) were
      identical at the COII region; this sequence indicates that diagnostic sites
      previously suggested for gorilla subspecies may be valid. Low variability was
      found within the D-loop region from a subset of the individuals (n = 15)
      sequenced for COII. Haplotype frequencies differed between the two habitats,
      suggesting a level of population subdivision that may have demographic
      consequences. These results also support the distinction of two distinct clades
      of gorillas comprised of western populations (G. g. gorilla) and eastern
      populations (G. g. graueri and G. g. beringei). Future management of Kahuzi-Biega
      National Park should ensure that sufficient habitat remains to prevent further
      genetic isolation of gorillas in the montane section of the park.

PMID- 9542161
TI  - Nine new cases of reciprocal translocation in the domestic pig (Sus scrofa
      domestica L.).
AB  - Nine pigs with decreased litter size or sired by boars with decreased litter size
      were found to be reciprocal translocation carriers. Four Large White animals (two
      females and two males) demonstrated translocations involving chromosomes 1 and 9
      (1p-;9p+), 11 and 13 (11q+;13q-), 3 and 13 (3;13)(p1.5;q3.1), and 15 and 17
      (15;17)(q1.3;q2.1). Two Large White x Pietrain terminal boars demonstrated
      translocations involving chromosomes 11 and 16 (11;16)(p1.4;q1.4), and 6 and 14
      (6;14)(q2.7;q2.1). The (9;15)(p2.4;q1.3) and (6;16)(q1.1;q1.1) translocations
      were found in a Large White x French Landrace boar, and in a commercial male line
      boar with decreased litter size, respectively. A Gascon breed boar with reduced
      prolificacy also had an abnormal karyotype, namely 38 XY, rcp(1;6)(q1.2;q2.2).
      Reduction in prolificacy was estimated accurately in cases 3, 5, 6, 7, and 9
      (35%, 30%, 35%, 41%, and 56%, respectively). Rcp(1;6)(q1.2;q2.2) and
      rcp(6;16)(q1.1;q1.1) seemed to have been of de novo origin.

PMID- 9542162
TI  - Analytical aspects of population-specific DNA fingerprinting for individuals.
AB  - An emerging problem of some interest is whether we can determine the population
      membership of a single individual, using a population-specific "genetic
      fingerprint." The levels of accuracy and precision required are beyond the reach
      of allozyme analysis, and attention has shifted to DNA polymorphisms. There are
      different types of DNA markers available for population surveys: RFLPs, mini- and
      micro-satellites, and RAPDs, and each type has its own strengths and weaknesses.
      We present a generic analysis that relates gene pool separation to our ability to
      assign individuals, an analysis that does not depend on the type of marker. We
      then review strengths and weaknesses of different DNA markers, in the context of
      DNA fingerprinting. Codominant loci are best. It is possible to gain more
      information per marker with multiallelic loci, but diminishing returns set in
      rapidly, and it is better to add loci. A modest number of independent loci is
      best, each locus with a modest number of alleles and with each allele in modest
      frequency.

PMID- 9542163
TI  - Short beak: a new autosomal recessive semilethal mutation in Japanese quail.
AB  - Short break (SBK) is a new semilethal mutation of Japanese quail (Coturnix
      japonica). The SBK individuals are characterized externally by short breaks,
      shanks, and digits. The shank is also thicker than the wild type. The shape of
      the mutant beak does not show a parrotlike appearance, contrasting with that of
      other poultry chondrodystrophic mutants reported in the literature. Bones in the
      fore and hind limbs of the SBK mutant are also shorter than the wild types. The
      humerus and ulna in the wing are significantly thicker than the wild types. Other
      bones in the wing and leg show approximately the same thickness as the wild
      types. The majority of the SBK mutants die at the late embryonic stage. Some
      chicks can hatch with no assistance, but almost all die around 3 days of age.
      However, a part of the SBK individuals (5.3%, 8/151) reach sexual maturity and
      can reproduce. Genetic analyses revealed that the SBK mutation is controlled by
      an autosomal recessive gene. The proposed gene symbol is sbk. The sbk gene is
      allelic to the previously reported stumpy-limb (sl) gene that expresses a
      somewhat similar phenotype to the SBK.

PMID- 9542164
TI  - Genetic variation and population genetic structure in Trifolium pratense.
AB  - Trifolium pratense (red clover) is a short-lived herbaceous plant native to
      southeastern Europe and Asia Minor. Widel used in agriculture, T. pratense is
      cultivated as an annual, winter annual, or biennial. It blooms from mid-spring to
      early fall and is insect pollinated and self-incompatible. Seeds are mammal and
      bird dispersed. Naturalized populations of T. pratense occur along roadsides and
      in old fields as well as native grasslands. Allozyme diversity and population
      genetic structure were determined for nine populations of T. pratense. Results
      from 13 allozyme loci indicate that genetic diversity is higher and population
      divergence is lower than expected based on the life-history characteristics of
      the species. We conclude that the high levels of genetic diversity found within
      populations of T. pratense suggest that these are not newly established founder
      populations, and that the low levels of genetic divergence seen among populations
      are probably due to high rates of gene flow among populations as a result of seed
      and pollen movement.

PMID- 9542165
TI  - Karyotypic analysis of N-banded chromosomes of diploid alfalfa: Medicago sativa
      ssp. caerulea and ssp. falcata and their hybrid.
AB  - Chromosomes of two diploid (2n = 2x = 16) subspecies of Medicago sativa, ssp.
      caerulea and ssp. falcata, and their hybrid were studied using an N-banding
      technique. This study was undertaken to develop an N-banded karyotype of ssp.
      caerulea and ssp. falcata, and determine if the same technique could be used to
      identify parental chromosomes in hybrids. The chromosomes of ssp. falcata have
      only centromeric N bands and thus individual chromosomes could not be identified.
      However, chromosome-specific bands were observed in ssp. caerulea enabling the
      identification of each of the eight pairs of chromosomes and the development of
      an idiogram. All chromosomes have a centromeric band and a telomeric band in the
      short arm. All of the chromosomes, except chromosomes 7 and 8, have interstitial
      bands in their long arms and chromosome 5 has two faint interstitial bands in its
      long arm. The satellited chromosome is easily distinguished due to the secondary
      constriction and characteristic band at the nucleolar organizer region. The
      differences in banding patterns between these subspecies makes it possible to
      distinguish chromosomes from each other in their hybrids. This is the first
      report of the use of N banding to identify the diploid chromosomes of M. sativa
      ssp. caerulea and ssp. falcata.

PMID- 9542167
TI  - Similarity of monosaccharide, oligosaccharide and polysaccharide structures in
      gum exudate of Anacardium occidentale.
AB  - The gum exudate from the Brazilian cashew-nut tree (Anacardium occidentale)
      contained traces of the reducing sugars, rhamnose (0.005%), arabinose (0.03%),
      mannose (0.007%), galactose (0.03%), glucose (0.02%), beta-D-Galp-(1-->6)-alpha
      beta-D-Gal (0.05%), alpha-L-Rhap-(1-->4)-alpha beta-D-GlcA (0.008%) and alpha-L
      Rhap-(1-->4)-beta-D-GlcpA-(1-->6)-beta-D-Galp-(1-->6 )-alpha beta-D-Gal (0.008%).
      Rhamnose, arabinose, glucose and the three oligosaccharides are components of the
      side-chains of the gum polysaccharide, which has a main chain of (1-->3)-linked
      beta-D-Galp units. The structure of this polysaccharide was determined and found
      to differ from that previously reported for the gum of a tree growing in India,
      lacking units of 4-O-methylglucuronic acid. Other new side-chain structures were
      characterized, particularly -alpha-D-Galp-(1-->6)-D-Galp- and alpha-L-Araf-(1-
      >6)-D-Galp-).

PMID- 9542166
TI  - The enolases of ice plant and Arabidopsis contain a potential disulphide and are
      redox sensitive.
AB  - The simulated structures of the enolases of Arabidopsis and the common ice plant
      contain a pair of Cys residues in the correct orientation to form a disulphide
      bond. Formation of this disulphide might be expected to affect the positioning of
      several residues in the active site. The enzyme in crude extracts of these two
      plants is activated by oxidation. Apparently formation of the disulphide
      crosslink enhances catalysis. The enolases from tomato leaves, maize roots and
      castor bean embryos lack one of these Cys residues and are not redox sensitive.
      It seems possible that enolase is redox-regulated by a cytosolic thioredoxin
      system in a limited number of plant species including ice plant and Arabidopsis.

PMID- 9542168
TI  - Antifungal and larvicidal meroterpenoid naphthoquinones and a naphthoxirene from
      the roots of Cordia linnaei.
AB  - Three new meroterpenoid naphthoquinones, the known cordiaquinone B and a new
      naphthoxirene have been isolated from the roots of Cordia linnaei. Their
      structures were established by spectrometric methods including EI, D/CI and FAB
      mass spectrometry, 1H, 13C and 2D NMR experiments. The naphthoquinones showed
      activity against Cladosporium cucumerinum, Candida albicans and the larvae of the
      yellow fever-transmitting mosquito Aedes aegypti, while the naphthoxirene
      derivative was found to be inactive in the same bioassays.

PMID- 9542169
TI  - Xyloglucan from xylem-differentiating zones of Cryptomeria japonica.
AB  - Xyloglucan was isolated from xylem-differentiating zones of Cryptomeria japonica.
      Endo-1,4-beta-glucanase digestion of the xyloglucan gave a series of
      oligosaccharides. These oligosaccharides were purified by gel permeation
      chromatography and normal-phase HPLC. Glycosyl-residue composition and glycosyl
      linkage composition analyses. 1H NMR spectroscopy and FAB-mass spectrometry of
      the oligosaccharides showed that the xyloglucan was composed of five kinds of
      oligosaccharide. These oligosaccharides are commonly found in xyloglucan from
      dicot plants and are characterized as XXXG, XXLG, XXFG, XLLG and XLFG. These
      results suggest that xyloglucan from gymnosperms has similar structure to that of
      dicots.

PMID- 9542170
TI  - An 8-hydroxylated external flavone and its 8-O-glucoside from Becium
      grandiflorum.
AB  - The major vacuolar flavonoid of a greenhouse-grown plant of Becium grandiflorum
      has been identified as the 8-O-glucoside of isothymusin (5,8,4'-trihydroxy-6,7
      dimethoxyflavone), while the major external flavonoids in the diethyl ether
      surface wash of the same plant are found to be isothymusin and cirsimaritin (5,4'
      dihydroxy-7,8-dimethoxyflavone). Although isothymusin is already known as a
      conversion product of thymusin (5,6,4'-trihydroxy-6,7-dimethoxyflavone) formed by
      means of the Wessely-Moser rearrangement, this is the first report of isothymusin
      as a plant constituent, both as aglycone and glycoside. The biogenetic and
      chemotaxonomic implications of the occurrence of these flavonoids in
      B.grandiflorum are briefly discussed.

PMID- 9542171
TI  - Haemolytic glycoglycerolipids from Gymnodinium species.
AB  - Glycoglycerolipids derived from microalgae can be a source of biologically active
      substances including toxins. Such glycolipids were analysed in two isolates of
      toxic marine dinoflagellates from European waters. The lipids of Gymnodinium
      mikimotoi contained 17% of monogalactosyl diacylglycerol (MGDG) and digalactosyl
      diacylglycerol (DGDG), while in Gymnodinium sp. the proportion was 35%. MGDG and
      DGDG from both species were haemolytic. The major unsaturated fatty acid in both
      algal glycolipids was 18:5 omega 3.

PMID- 9542172
TI  - Three naphthalenes from root bark of Hibiscus syriacus.
AB  - Three new naphthalenes, designated as syriacusins A-C, were isolated from the
      root bark of Hibiscus syriacus. These compounds were identified as 2,7-dihydroxy
      6-methyl-8-methoxy-1-naphthalenecarbaldehyde, 2-hydroxy-6-hydroxymethyl-7,8
      dimethoxy-1-naphthalenecarbaldehyde, 1-carboxy-2,8-dihydroxy-6-methyl-7
      methoxynaphthalenecarbolactone (1-->8), respectively, on the basis of various
      spectral studies. The compounds inhibited lipid peroxidation with IC50s of 0.54,
      5.90 and 1.02 micrograms ml-1, respectively. The first compound also showed
      cytotoxicity against some human cancer cell lines with an ED50 of 1.5-2.4
      micrograms ml-1.

PMID- 9542173
TI  - Mono-THF ring annonaceous acetogenins from Annona squamosa.
AB  - Continuing work on the bark of Annona squamosa Rich. (Annonaceae), directed by
      the brine shrimp lethality test (BST), has resulted in the isolation of three new
      Annonaceous acetogenins, 4-deoxyannoreticuin, cis-4-deoxyannoreticuin, and (2,4
      cis and trans)-squamoxinone. The first two are additional examples of acetogenins
      isolated from this plant species which contain the unusual feature of an oxygen
      functionality at the C-9 position. They have a hydroxylated mono-THF ring with
      respective threo/trans/threo and threo/cis/threo relative stereochemistries. The
      latter compound is a ketolactone mixture which has the same relative
      stereochemistry around the THF ring and the same spatial relationship between the
      THF ring and the hydroxyl group along the aliphatic chain as 4-deoxyannoreticuin,
      but is two methylene units longer. Additionally, the isolated hydroxyl group is
      at C-11, while the THF ring starts at C-17, instead of at C-9 and C-15,
      respectively, as for the first two compounds. All three compounds showed
      moderate, but significant, cytotoxicities against a panel of six human tumor cell
      lines with (2,4 cis and trans)-squamoxinone showing promising selectivity against
      the pancreatic cell line (PACA-2).

PMID- 9542175
TI  - [Prospective registry of cerebrovascular diseases. Characterization of patients
      and methodology evaluation].
AB  - Hospital-based stroke data banks can contribute to a better management of stroke
      patients with consequent reduction of associated morbidity and mortality.
      OBJECTIVE: The characterisation of stroke patients and validation of the hospital
      stroke registry. SETTING: Hospital S.Pedro, Vila Real, a secondary neurological
      referral centre for 450.000 inhabitants of interior north Portugal. PATIENTS AND
      METHODS: Analysis of data collected over one year of a prospective computerised
      stroke registry. Evaluation of completeness of the registry by independent
      analysis from emergency room data files and percentage of items entirely filled
      up. RESULTS: in a one year period were registered 349 patients (186 F; 163 M)
      with a mean age at stroke of 69 years. The majority (73.3%) lived in the hospital
      district. Most patients went directly to the hospital from their homes, and in
      the first 24 hours of symptoms onset. Cerebral infarction was diagnosed in 35.2%
      of patients, followed from lacunas in 24.6% and hypertensive haemorrhages in
      22.3%. Arterial hypertension was found in 60.1% of cases, there were 11.4% of
      deaths and a Rankin score > 3 was present at hospital discharge in 39.5% of
      patients. There was a decrease in the register during the one-year period,
      evaluated comparing two months of emergency room files; we found a missing rate
      of protocols items varying from 0.8% and 8.8%. CONCLUSIONS: Hospital-based stroke
      data banks can provide the best available information on stroke patients
      characteristics and the presence of stroke risk factors. Registry protocols must
      be kept simple, easy to fill and periodically surveyed in order to lessen the
      number of missing items.

PMID- 9542174
TI  - Minor daphnane-type diterpenoids from Wikstroemia retusa.
AB  - In addition to huratoxin, pimelea factor P2, and wikstroelides A-G from the fresh
      bark, eight daphnane-type diterpenoids, wikstroelides H-O, were isolated from the
      bark and stem, and their structures established. Cytotoxicity was assayed on some
      wikstroelides.

PMID- 9542176
TI  - [Angiography in thoracic outlet syndrome].
AB  - The thoracic outlet syndrome is a changeable clinical syndrome caused by
      compression of the neurovascular bundle of the upper extremity, within the
      cervicoaxillary channel. From April 1980 through May 1995, 24 patients with
      clinical thoracic outlet syndrome were evaluated by selective arteriography. The
      diagnosis was confirmed in seven patients, in 14 the exam was normal and in the
      last three cases another arterial pathology was detected--subclavian artery
      occlusion, subclavian artery kinking and vertebral steal syndrome. The authors'
      aim is to emphasize arteriography as a diagnostic exam for thoracic outlet
      syndrome, very useful in the detection and localization of arterial compression.
      It also allows the diagnosis of other arterial entities.

PMID- 9542177
TI  - [Analysis of the reactive capacity of intracerebral circulation with CO2. A
      method easily performed].
AB  - Maintenance of cerebral perfusion pressure is a prerequisite for the prevention
      of cerebral ischaemia. Physiological fluctuations in systemic perfusion pressure
      are compensated by cerebrovascular autoregulation. Cerebral perfusion reserve may
      be determined by assessing changes in cerebral blood flow using vasodilating
      stimuli. Transcranial Doppler has been used to assess cerebral blood flow speed
      in response to those stimuli. We describe a method using Transcranial Doppler
      with CO2 to analyse cerebral vasoreactivity. The method can be useful to
      determine hemodynamic reserve in different cerebral ischaemic diseases.

PMID- 9542178
TI  - [Regulation mechanisms of bone metabolism].
AB  - The bone is continuously in a remodelling process. Bone mass is maintained in a
      continuous balance between its destruction and formation. Bone remodelling
      proceeds in a highly regulated cycle in which osteoclasts adhere to bone and
      subsequently remove it by acidification and proteolytic digestion and the
      osteoblasts secrete a organic matrix which is calcified into new bone. Bone
      remodelling is the cellular basis of bone metabolism. Pathological changes in
      many metabolic bone diseases can be explained by abnormalities at some point of
      the remodelling cycle. The mechanisms of regulatory bone metabolism involve the
      availability of a number of minerals and ionic homeostasis, systemic hormones and
      numerous local factors. In this work the general pattern of bone remodelling and
      the cellular mechanisms of bone resorption and formation are briefly described.
      The role of systemic and local factors in the regulation and coupling of these
      two processes is also reported.

PMID- 9542179
TI  - [Orthostatic tachycardia syndromes].
AB  - Orthostatic tachycardia may be due to several physiologic abnormalities. Normal
      regulation of cardiac frequency in relation to postural changes is described;
      main causes of orthostatic tachycardia are described, in particular hypovolemia,
      beta-adrenergic hypersensitivity and segmental autonomic neuropathy. The current
      therapeutic attitudes are discussed.

PMID- 9542180
TI  - [Adhesive lumbar arachnoiditis].
AB  - Spinal arachnoiditis, an inflammatory process involving all three meningeal
      layers as well as the nerve roots, is a cause of persistent symptoms in 6% to 16%
      of postoperative patients. Although spinal surgery is the most common antecedent
      associated with arachnoiditis, multiple causes have been reported, including
      infection, intrathecal steroids or anesthetic agents, trauma, subarachnoid
      hemorrhage and ionic myelographic contrast material--both oil soluble and water
      soluble. In the past, oil-based intrathecal contrast agents (Pantopaque) were
      associated with arachnoiditis especially when this material was introduced into
      the thecal sac and mixed with blood. Arachnoiditis is apparently rarely
      idiopathic. The pathogenesis of spinal arachnoiditis is similar to the repair
      process of serous membranes, such as the peritoneum, with a negligible
      inflammatory cellular exudate and a prominent fibrinous exudate. Chronic adhesive
      arachnoiditis of the lower spine is a myelographic diagnosis. The myelographic
      findings of arachnoiditis were divided into two types by Jorgensen et al. In type
      1, "the empty thecal sac" appearance, there is homogeneous filling of the thecal
      sac with either absence of or defects involving nerve root sleeve filling. In
      type 2 arachnoiditis, there are localized or diffuse filling defects within the
      contrast column. MRI has demonstrated a sensitivity of 92% and a specificity of
      100% in the diagnosis of arachnoiditis. The appearance of arachnoiditis on MRI
      can be assigned to three main groups. The MRI findings in group I are a
      conglomeration of adherent roots positioned centrally in the thecal sac. Patients
      in group II show roots peripherally adherent to the meninges--the so called empty
      sac. MRI findings in group III are a soft tissue mass within the subarachnoid
      space. It corresponds to the type 2 categorization defined by Jorgensen et al,
      where as the MRI imaging types I and II correspond to the myelographic type 1.

PMID- 9542181
TI  - [Models and transformations of the physician's role].

PMID- 9542182
TI  - [Peptic ulcer and its treatment modalities in medicine].

PMID- 9542183
TI  - [Murine typhus in Portugal].
AB  - Murine typhus or endemic typhus is a wide spread infectious disease, with a low
      prevalence in developed countries, but surely underdiagnosed. Its relative
      benignity, the similarity to other infectious diseases and the discretion of its
      epidemiologic chain, as well as the usual unexpectedness of its existence, makes
      its diagnosis more difficult. The clinical presentation and evolution of this
      case illustrate the necessity of being aware of this nosological entity.

PMID- 9542184
TI  - [Palpebral metastasis revealing a gastric adenocarcinoma].
AB  - The authors present a case of a gastric adenocarcinoma in which the major
      manifestation was cutaneous metastases of the eyelids--in a review of the
      literature, no reports were found. Based upon this unusual case and in light of
      present knowledge, we decided to revise the concept of cutaneous metastases
      secondary to internal neoplasia, in particular, these with a gastric
      localization.

PMID- 9542185
TI  - [Guideline for the diagnosis of brain death].

PMID- 9542186
TI  - [Methods of endoluminal treatment of urethral stenosis up to the end of the 19th
      Century].
AB  - Ever since Hippocrates, physicians have managed patients that suffered from
      urethral stricture. To that end, genius and imagination put to the service of
      scientific knowledge, have produced numerous apparatus, instruments and methods
      of a varied nature, with the aim of allowing urine passage through the strictured
      urethra. Illustrious names such as Andres Laguna or Francisco Diaz, and other not
      so well known. Spanish and foreigners, are mentioned in this paper in an intent
      to contribute a brief view on the evolution of the methods used to treat urethral
      stricture up to the end of the 19th Century.

PMID- 9542187
TI  - [Lasers as an alternative to the endoscopic surgery in BPH].
AB  - Neodymium laser (Nd:YAG) has been used for prostatic coagulation. New contact
      tips have been developed in order to cause vaporization of the prostate. With the
      objective to examine the effectiveness and safety of 2 new laser procedures. ITT
      (interstitial thermotherapy) and Sidefocus Technique, in patients with BPH, we
      have participated in a prospective, international, multicenter study comparing
      these technique with TURP and prostatic incision. A total of 80 patients
      suffering from symptomatic BPH in our center were randomized for the four
      procedures as follow: ITT (18): sidefocus technique (21), incision (20) and TURP
      (21). Inclusion criteria were at least 50 years old, prostate between 20 and 60
      g, maximum peak-flow < or = 12 ml/s, and I-PSS > or = 15. The patient's
      pretreatment evaluation consisted in World Health Organization symptom score and
      quality of life, digital rectal examination, transrectal, ultrasound, PSA, urine
      culture, prostatic biopsy if malignity suspected, uroflowmetric parameters and
      residual volume. Follow-up was performed using the same pretreatment parameters
      at one month, three months and six months. Statistical analysis was performed
      using ANOVA test and Student-Newman-Keul test. Symptom score decreased
      significantly in all groups. Peak flow rate increase was observed in the four
      groups but without statistical significance in both laser techniques. Results at
      the sixth month control comparing peak-flow rates are significantly more
      favourable for endoscopic surgical techniques (TURP and incision). Other
      flowmetric parameters, days of hospital stay, duration of catheter drainage,
      symptom scores and morbidity are analyzed.

PMID- 9542188
TI  - [Evaluation and treatment of closed renal trauma].
AB  - Renal trauma accounts for more than 50% of all genitourinary trauma cases, nearly
      90% of them corresponding to blunt trauma. Incidence is higher in male (3:1
      ratio); is more frequent between the second and third decades; and predominantly
      affects the left side. Our group analyzed 89 cases of blunt renal trauma seen in
      our service between 1983 and 1996 with the purpose of determining the choice
      imaging studies, indications and type of management. Based on severity, injuries
      were rated in 5 grades using the classification of the Organic Injuries Survey
      Committee (OIS) from the American Association of Surgery in Trauma (AAST). We
      analyzed the etiology, clinical findings, prior renal conditions, associated
      injuries, radiologic studies and treatment instituted. CAT was considered the
      choice diagnostic technique for trauma rating since it permits greater definition
      of renal injury grade, as well as the associated abdominal and thoracic injuries.
      Most renal traumas were mild in severity, and evolved favourably with
      conservative treatment. In renal trauma grades IV and V, surgery is the
      recommended therapeutic approach, always preferring the most conservative
      criteria.

PMID- 9542189
TI  - [Immunotherapeutic treatment for metastatic renal carcinoma].
AB  - Immunotherapy management for advanced renal carcinoma has awaken a growing
      interest over the last few years. Based on Atzpodien's studies, in December 1994
      a protocol was initiated in our centre for the treatment of metastatic renal
      carcinoma, using subcutaneous alpha interferon, subcutaneous Interleukin-2 and
      endovenous 5-Fluorouracil. The present report analyzes all six cases included in
      the protocol and their results.

PMID- 9542190
TI  - [Influence of sex differences in biological aggressivity of bladder urothelial
      tumor at first diagnosis].
AB  - RATIONALE: To investigate whether, in the same way incidence is affected,
      biological aggressiveness of bladder cancer at diagnosis is greater in men than
      in women. METHOD: Using data from a retrospective study on urothelial cancer of
      the bladder between 1975 and 1991 in La Rioja (Spain), an estimate was made of
      total Relative Risk, Mantel-Haenszel relative weighted risk and Greenland-Robins
      95% confidence interval of suffering infiltrant bladder cancer in male versus
      female, assuming that the tumour affecting the muscle layer was infiltrant.
      RESULTS: Total Relative Risk (1.05). Mantel-Haenszel relative weighted risk
      (1.08), and Greenland-Robins confidence interval (0.65-Relative Risk-1.08).
      CONCLUSIONS: It is concluded that sex differences have no influence on the risk
      to develop infiltrant urothelial cancer of the bladder at diagnosis.

PMID- 9542191
TI  - [Acute scrotum without technology].
AB  - The highly developed diagnostic technologies of our time applied to acute scrotum
      is not readily available in many of our hospitals. With the purpose of evaluating
      our results in the diagnosis and treatment of this nosologic entity, and to
      compare them with those reported by other hospitals where modern technologies are
      being used, our group revised all patients referring this condition who were
      given emergency treatment by the urologist on call during the first 100 months of
      our unit. An analysis is made of the etiology, patient's age, disease location,
      time of evolution, diagnosis, treatment received and final outcome. The
      epidemiological data obtained is similar to other series published, except for
      the hydatid torsion, which was more frequent than previously reported. In cord's
      torsion, a similar background should be considered a poor prognostic factor. In
      summary, the left testicle is more exposed to the various acute scrotal diseases.
      Surgery is an attractive option for hydatid torsion. Finally, an earlier
      intervention in the event of suspicious cord torsion remains the most important
      factor in the prognosis. Our results, using no state-of-the-art diagnostic
      technologies, are similar to other series and we see no trend towards unnecessary
      surgical examination.

PMID- 9542192
TI  - [Treatment of effort stress incontinence using a mechanical procedure. Personal
      technique].
AB  - On March 14th 1992, a female patient (P.C.O.) with CR 167584, underwent surgery
      for urinary exertional incontinence. We followed an original technique as a first
      (worldwide?) experience, using a pneumatic stapler designed for the management of
      this condition. The approach is vaginal, the active end of the stapler is
      introduced into the cavity and propped up against the anterior side of this organ
      close to the urethra: from this point and once the position is secured, the
      devise is pressed against the internal side of the pubis and a staple is
      projected fastening the vagina's ceiling to the interior side of the pubis. A
      total of eight procedures were performed, but only the first patient maintains a
      steady continence as the staple stays in the same position it was planted. In all
      remaining cases, the staples fell off over the subsequent weeks and the patients
      returned to the early incontinence state. The reasons for the inefficacy of this
      first prototype are analyzed, providing an explanation for the rationale behind
      this report four years after the experience.

PMID- 9542193
TI  - [Vesicoureteral tuberculosis. Apropos of a case].
AB  - A case of vesicoureteral tuberculosis is described. The clinical onset was like a
      tumor of this localization, with overlapping of clinical symptoms and radiologic
      findings. The histological study and the histochemical stains was the key to the
      diagnosis. We think that the coincidence of both clinical and radiologic
      findings, justified the interest of the case in de differential diagnosis.

PMID- 9542194
TI  - [Intrascrotal lymphangioma: report of 2 cases and review of the literature].
AB  - Congenital lymphatic disease with scrotal location is particularly uncommon in
      adults and, in general, requires an exhausting differential diagnosis of
      testicular and paratesticular masses; among them, the lymphangioma is
      exceptional. Diagnosis is based on signs and symptoms, evolution and radiological
      studies such as ultrasound and computerised tomography as well as characteristic
      findings in the anatomopathologic study such as cystic dilation with endothelial
      walls and lymph content with no signs of malignancy. Treatment is usually
      surgical. Two cases of intrascrotal lymphangioma, one at Buck's fascia level in
      the corpus cavernosum and the other one at the subdermal tissue in the scrotal
      wall are contributed. An analysis is made of the usefulness of the different
      imaging diagnostic methods, and complete surgical resection of the lesion is
      proposed as the choice therapy.

PMID- 9542195
TI  - [Ossification in corpus cavernosum and review of the literature].
AB  - Contribution of one study case of corpus cavernosum ossification including a
      literature review and analysis of signs and symptoms as well as the potential
      therapeutic options in that condition. The conversion of the albuginea's
      connective tissue into bone is the pathological end of La Peyronie's disease.

PMID- 9542196
TI  - [Testicular epidermoid cyst].
AB  - Epidermoid cysts are benign tumours that can affect testicles. Incidence is rare,
      having been described until now in less than 200 cases. Contribution of one study
      case of testicular epidermoid cyst and discussion of issues on histogenesis,
      ultrasound diagnosis and therapy approaches.

PMID- 9542197
TI  - [Spanish Association of Urology National Congress. Valladolid, June of 1997.
      Asystole donor].

PMID- 9542198
TI  - [Echography in the screening of adrenal expanding pathology. Practical case].

PMID- 9542199
TI  - [Relationship between calcium intake and bone mass].

PMID- 9542201
TI  - [Lymphocyte activation in tuberculous pleuritis . Correlation with adenosine
      deaminase (ADA), peripheral blood lymphocytes, T cell receptor subfamilies,
      radiographic extension and levels of Il-6 and soluble Il-2 receptor].
AB  - We determined in 14 patients with pleural tuberculosis total lymphocyte count, T
      subsets and NK cells (CD56) in pleura and blood and it was found a preferential
      accumulation in pleura of CD3 T lymphocytes, TCR alpha beta, mainly CD4 subset,
      but not T or NK cells. In 5 pleuritis it was studied 40% of V beta TCR
      subfamilies in blood and pleura and in 2 pulmonary tuberculosis and one pleuritis
      all V beta and V alpha TCR subfamilies (trough PCR), without be observed a clear
      clonal expansion. It was not observed correlation among a) pleural and blood
      lymphocyte cellularity b) the amount of pleural effusion and the existence of
      lymphopenia or tuberculinic anergia c) levels of ADA and percentage of CD3 and
      CD4 cells in pleura. In 7 out 11 pleuritis a high expression of IL-2 receptor
      (CD25) was observed. In 24 patients with pleural and pulmonary tuberculosis there
      was not correlation between levels of SIL-2R and IL-6 and radiographic extension.

PMID- 9542200
TI  - [Are food intake and life styles related with bone mass in fertile women?].
AB  - BACKGROUND: To study the relationship between current and adolescent calcium
      intake and bone mineral density (BMD) in 76 premenopausal women of 42 y. with
      regular menses and without pathologies associated with body weight, body
      morphology or BMD. METHODS: Was measured: the lumbar and femoral BMD by dual
      energy X-Ray absorptiometer, calcium and protein intake by a week frequencies
      questionnaire, and calciuria. Obesity, exercise, alcohol, tobacco and family
      history of osteoporosis were considered. Levels of BMD < -1SD was considered as
      osteopenia. RESULTS: Calcium intake average was 989 mg/day, 62% by dairy. Twenty
      five percent presented osteopenia in some bone site. BMD was not correlated with
      calcium or protein intake, calcium/protein nor calciuria. No differences was
      found between normal and osteopenic group for any of the studied variables,
      except lower body mass index in the femoral osteopenic group. Those women who
      decreased the calcium intake from adolescence had 8.2% less femoral BMD tha those
      who increased the consumption (p = 0.05). CONCLUSION: Current and adolescent
      calcium intake, family history of osteoporosi calciuria, and exercise have not
      found useful as screening of osteopenia in premenopausal women with moderated
      exercise level and low consumption of alcohol and tobacco.

PMID- 9542202
TI  - [Exclusion causes to thrombolytic treatment in myocardial infarction].
AB  - BACKGROUND: Only one third of patients who have suffered a myocardial infarction
      can benefit from thrombolytic treatment in the daily clinic practice. The aim of
      this study is to know the percentage of patients who were treated in a General
      Hospital and the main exclusion causes to receive thrombolytic treatment.
      METHODS: A descriptive study in patients with infarction who were admitted to the
      Critical Care Unit of a 550 beds Hospital between September-95 and August-96.
      RESULTS: 188 patients were admitted with suspicion of myocardial infarction. The
      50.53% of them received thrombolytic treatment. The main exclusion causes to
      receive this treatment were: delay of the patient (18.10%), normal ECG or
      descended ST (16.50%), contraindications (8%), patient's refusal to receive
      treatment (0.53%) an uncertain indication of therapy (6.40%). CONCLUSIONS: A high
      percentage of patients received thrombolytic therapy, maybe because these drugs
      can be used until 12 hours the infarction and they haven't limit of age.

PMID- 9542203
TI  - [Efficacy of ritonavir in HIV positive patients pretreated with nucleoside
      analogues].
AB  - The virologic and immunologic efficacy of ritonavir, an HIV protease inhibitor,
      was examined in 14 HIV-infected patients with a mean CD4+ cell count of 183 x
      10(6)/l at baseline. All had been exposed to nucleoside analogs for longer than 6
      months; and ritonavir was added to previous ongoing antiretroviral drugs. A mean
      reduction of 1.5 logs was seen in plasma viral load 4 weeks after began
      ritonavir, and 9 (64.3%) of 14 patients achieved undetectable levels (< 4,000 HIV
      RNA copies/ml). A mean increase of 222 x 10(6) cells was observed in the CD4+
      count. Nine (64.3%) individuals reported side effects, although they did not
      force to stop the medication. In conclusion, the addition of ritonavir seem to be
      a reasonable alternative strategy in patients with advanced HIV disease and heavy
      previous exposure to nucleoside analogs.

PMID- 9542204
TI  - [Sjogren's syndrome: a new diagnostic approximation].
AB  - At presentation the history of a 51 years old woman with xerostomia and dry
      keratoconjunctivitis sicca (KCS) with a development of ten months. Investigations
      revealed the presence in serum of antibodies against cytoplasmic antigens SS-A
      (Ac anti-Ro/SS-A), antinuclear antibodies (ANAS), and rheumatoid factor (RF). The
      test with Rose of Bengal was positive, and in the salivary gammagraphy made with
      pertecnate-99 m Tc it was observed a decreased of the captation and excretion of
      the designer for the salivary glands. The histopathology and immunohistochemical
      study of the minor salivary glands showed the presence of a focal lymphocytic
      sialadenitis (fls) and a predominance of lymphocytes CD4+. It was diagnosed a
      primary Sjogren a Syndrome (SSP) and the patient was treated with salivary
      substitutes and artificial tears. We analyse the current diagnostic criteria of
      the group of studies of the European Community for the SS. We emphasize the
      importance of the histologics and immunohistochemical study that with the rest of
      the complementary test will let us to distinguish not only the different forms of
      presentation of the illness, but also those of all the patients with pathologies
      which are very prevalent in our environment nowadays, such as the infections by
      virus C of the hepatitis (VCH) and the human immunodeficiency (VIH).

PMID- 9542205
TI  - [Secondary encephalopathy due to exposure to organic solvents:
      psychopathological, neuropsychological and neuroimaging findings].
AB  - Chronic exposure to organic solvents may cause permanent cognitive impairment.
      The nonspecify of neurological signs as the abnormalities of neurophysiological
      tests and morphological neuroimaging techniques have oblige the use of clinic
      neuropsychology in the monitorization of the neurotoxicity cause by these
      substances. The new modern functional neuroimaging techniques can contribute to
      the diagnosis of brain lesions caused by the exposure to organic solvents. We
      report a case that clearly supports this hypothesis as we emphasize the
      correlation found between clinical symptoms and the deficits obtained after the
      study of cerebral blood flow with single photon emission computed tomography
      (SPECT).

PMID- 9542206
TI  - [Psoas abscess, a rare and forgotten entity. Report of 6 cases].
AB  - The psoas abscess is an entity, some times forgotten in our daily clinical
      practice. The gram-positive microorganisms are the most frequent, and S. aureus
      is the most important pathogen. We present a retrospective study of six cases. In
      our revision, five patients were women (83.3%), and one man (16.6%), with a
      median age of 65.83 years. The associated pathology were vertebral in four
      patients (66.6%), and urologic in two of them. The main symptoms were fever and
      lumbar pain. All the patients were diagnosed by CT. The correct identification of
      the microorganisms, and the prompt use of the antibiotherapy associated to
      surgery, helped to a total recuperation of this patients.

PMID- 9542207
TI  - [Primary endobronchial non-hodgkins lymphoma: description of a case and review of
      the literature].
AB  - We report a case of primary endobronchial non-Hodgkin Lymphoma, an unusual
      extranodal lymphoma, in a 62 year old patient, which begins with malaise, marked
      respiratory symptoms and empyema. We especially discuss its diagnostic's criteria
      and its clinicoradiologic manifestations. We argue over its pathologic,
      immunohistochemical and cytogenetic features according to the REAL classification
      of lymphomas. On previous experience and the good response of this case, we
      propose chemotherapy followed radiotherapy may would be a suitable therapeutic
      approach.

PMID- 9542208
TI  - [Colony stimulating factors in chemotherapy induced neutropenic fever].
AB  - We review the randomized trials published so far comparing the use of colony
      stimulating factors (both G-CSF and GM-CSF) as adjunctive care in chemotherapy
      induced neutropenic fever. With this treatment a slight one day reduction in
      duration of neutropenia under 500 neutrophils per mm3 is observed; this effect
      seems to be more important in prolonged neutropenias. The number of days with
      fever remain unchanged. No clear benefit expressed as clinical and quality of
      life improvement or economical saving is proved. According to these results, and
      as previous recommendation about the use of colony-stimulating factors pointed
      out, the indications for administration of such cytokines in neutropenic fever
      are restrictive and its use could be acceptable only in patients with poor
      prognostic factors.

PMID- 9542209
TI  - [A regard of the epidemiology and etiology of malignant melanoma: current status
      and inquiries].

PMID- 9542210
TI  - [Asymptomatic pericardial effusion postirradiation].

PMID- 9542212
TI  - [Pancreatitis, thrombophlebitis and empyema complicating typhoid fever].

PMID- 9542211
TI  - [Peripartum cardiomyopathy].

PMID- 9542213
TI  - [Intestinal malabsorption as clinical presentation of systemic mastocytosis].

PMID- 9542214
TI  - [Effect of calcium channel antagonists in primary pulmonary hypertension in
      association with human immunodeficiency virus infection].

PMID- 9542215
TI  - [Multidrug resistant tuberculosis and AIDS].

PMID- 9542216
TI  - [High-dose amphotericin B in the treatment of rhino-cerebral mucormycosis: a case
      with an unusual evolution].

PMID- 9542217
TI  - [Tobacco addiction in respiratory outpatients].

PMID- 9542218
TI  - [Appraisal of the efficiency during the process of drug selection in Hospitals].

PMID- 9542219
TI  - [Resources of pediatric interest on the Internet].

PMID- 9542220
TI  - [An experimental study on the effects of maternal hyperphenylalaninemia on the
      central nervous system and behavior of offspring rats].
AB  - OBJECTIVE: This work attempts to study the cerebral alterations in rat offspring
      of hyperphenylalaninemic mothers, as well as the possibility of preventing them
      by means of administration of dietetic supplements of valine, leucine and
      isoleucine during the pregnancy. PATIENTS AND METHODS: An experimental study in
      two consecutive pregnancies of 18 Wistar rats was carried out. The first
      pregnancy serves as the control group. In the second pregnancy, an experimental
      hyperphenylalaninemia was provoked by means of injection of phenylalanine and
      chlorophenylalanine (phenylalanine-hydroxylase inhibitor). In half of the mothers
      during the second pregnancy the diet was supplemented with branched-chain amino
      acids. In the offspring rats, a histological cerebral study was performed
      (conventional electron microscopy and study of synaptosomes). A behavioral study
      (T-water maze) was also performed at birth and on the 35th and 65th days of life.
      RESULTS: The offspring of the group submitted to hyperphenylalaninemia were
      microcephalic (p = 0.0003) and had fewer synaptosomes that had a larger surface
      area (p = 0.0081 in newborn rats, p = 0.0028 on the 35th day of life) and of a
      more immature aspect (less vesicular content). In addition, alteration in the
      myelinization were detected. In the behavior test (65th day of life), the
      offspring of the mothers with hyperphenylalaninemia make significantly more
      mistakes (p = 0.0167) and they needed more time for their resolution (p = 0.059).
      None of these alterations could be prevented by the administration of supplements
      of branched-chain amino acids to the mother. These supplements resulted in a
      higher fertility rate, but this action results in affected young rats, so their
      administration seems to be counter-productive.

PMID- 9542221
TI  - [The determination in the blood of the enzyme neuron-specific enolase in children
      with acute encephalopathies: the prognostic value in neurological sequelae].
AB  - OBJECTIVE: The objective of this study was to evaluate if there is a correlation
      between blood levels of the enzyme neuron-specific enolase in children with non
      traumatic acute encephalopathies with severe alterations in consciousness and the
      neurological sequellae. PATIENTS AND METHODS: Neuron-specific enolase (EC
      4.2.1.11) activity in plasma was measured by radioimmunoassay in 9 children aged
      7 months to 5 years, who suffered acute encephalopathy and coma of non-traumatic
      origin. The etiology was acute viral encephalitis (n = 4), near drowning (n = 2),
      shock (n = 2) and cardiac arrest (n = 1). Blood samples were obtained between 24
      and 72 hours after the onset of encephalopathy. The neurological status was
      evaluated 18 months after the onset of encephalopathy in the 8 surviving patients
      (1 patient with brain death criteria died in the acute stage). RESULTS: Enzyme
      activities were significantly higher in the children who showed neurological
      sequelae (median 68.9 ng/ml, range 35.0-95.6, n = 4) than in those who did not
      present neurological abnormalities (median 15.8 ng/ml, range 9.7-18.7, n = 5),
      with p < 0.05. No differences were found between the latter and the control group
      (median 7.7 ng/ml, range 4.1-12.7, n = 10). CONCLUSIONS: It appears that the
      presence of elevated neuron-specific enolase in blood is predictive of
      neurological outcome in children with acute encephalopathies of non-traumatic
      origin.

PMID- 9542222
TI  - [The utility of gammagraphy with Tc 99-labelled dimercaptosuccinic acid (DMSA) in
      the protocol for studying urinary infection in a 2nd-level hospital].
AB  - OBJECTIVE: Not all hospitals in our country have their own nuclear medicine
      laboratory. Most small and medium size hospitals must arrange their radioisotope
      studies with private clinics. The objective of this study was to assess if a
      single DMSA scan performed after an acute infection in a group of patients chosen
      according to certain risk criteria would allow the selection of those who run the
      risk of progressive renal damage. PATIENTS AND METHODS: A descriptive and
      retrospective study of the clinical records of 65 patients under 14 years of age
      with urinary tract infection (UTI) seen at our institution between 1994 and 1995
      and on whom a DMSA scan had been performed was carried out. The study groups was
      formed by the fifteen children with scintigraphic findings compatible with renal
      scarring. The fifty children with normal DMSA scans were used as controls.
      RESULTS: Renal scarring was found more often in patients over one year of age (p
      < 0.05), in those with reinfections (p < 0.001) and in those kidneys with grade
      III vesicoureteral reflux (VUR, p < 0.05). The most severe lesions, with
      reduction of renal size, shape abnormalities and diminished uptake of the tracer
      were found together with VUR. The renal sonogram performed during the acute stage
      of the UTI was able to detect only four of the six children most severely
      affected. CONCLUSIONS: Delaying the practice of the DMSA scan until 6 months
      after the last episode of bacteriuria would allow selection of those patients at
      the highest risk of progressive renal damage. This guideline would reduce
      scintigraphic studies 30 to 90%, since it would avoid repeated studies in those
      children with abnormal findings in the acute stage. The practice of the
      radioisotope study only in a reduced subset of patients selected on the basis of
      risk criteria such as recurrent UTI, VUR or suspected pyelonephritis does not
      allow detection of all scars.

PMID- 9542223
TI  - [A longitudinal study of physical exercise practice in children. The influence of
      age, gender and socioeconomic level. The Working Group on Cardiovascular Risk
      Factors in Childhood and Adolescence].
AB  - OBJECTIVE: Physical exercise is recommended in order to reduce cardiovascular
      risk factors. PATIENTS AND METHODS: A longitudinal study was carried out. During
      the periods of 1989-1990 an 1995-1996, a questionnaire concerning extrascholastic
      physical exercise was given to 345 children of both sexes (188 males and 157
      females), classifying them into two groups according to their parents'
      socioeconomical status. RESULTS: We found and increase in the number of
      schoolchildren who did physical exercise (initial 17.97% and final 44.34%) in
      both sexes and both socioeconomical groups, as well as in the number of hours per
      week they spent exercising. Boys did physical exercise more frequently (initial
      study: 27.89% versus 13.37%, final study: 52.65% vs 40.86%) and they spent more
      hours per week than did girls. The same behavior was observed in the group of
      higher socioeconomical status. The probability of men doing physical exercise
      with respect to women was found to be statistically significant (initial study: p
      < 0.001, final study: p < 0.05), as well as in logistical regression between the
      non-performance of physical exercise and socioeconomical status (p < 0.001).
      CONCLUSIONS: In this longitudinal study it was found that with age there is an
      increment in the practice of physical exercise and in the hours spent on it. It
      was also found that males and individuals with a higher socioeconomical status do
      more physical exercise than females and those with a lower socioeconomical
      status.

PMID- 9542224
TI  - [The diagnostic value of echography in appendicitis in children].
AB  - OBJECTIVE: The purpose of this study was to analyze the possible usefulness of
      ultrasonography for the diagnosis of acute appendicitis in children and to
      compare this technique with the clinical signs classically employed in the
      evaluation of pain in the right lower quadrant (RLQ) in the emergency ward.
      PATIENTS AND METHODS: We prospectively analyzed 112 patients younger than 14
      years with suspected appendicitis. After a careful clinical record and physical
      and complementary studies were performed, we performed a ultrasonography of the
      RLQ on all patients a tubular, non-mobile, non-compressible image with a target
      image measuring 6 mm or more on the cut section was considered suggestive of
      appendicitis. After the initial clinical-radiological evaluation, the patients
      were either operated or included in a follow-up group. None of them were
      dismissed. The confirmation of the diagnosis of appendicitis was histological.
      RESULTS: Only 4 of the 14 factors analyzed showed a significant association with
      acute appendicitis (leukocytosis, left shift, abdominal RX film suggesting
      inflammation in the RLQ and ultrasonography positive for appendicitis), with
      ultrasonography being the technique with the highest diagnostic reliability
      (77.7% sensitivity and 94.8% specificity). The age of the patients with
      appendicitis was significantly lower than that of the patients without
      appendicitis. Nevertheless, we did not find any relationship between advanced
      appendicitis and factors such as age or time of evolution. CONCLUSIONS: After a
      clinical-ultrasonography evaluation, our negative appendectomy rate was 7% and
      the perforation/gangrenous appendicitis rate was 29%. We conclude that
      ultrasonography performed by trained professionals is a useful tool in the
      differential diagnosis of appendicitis in children.

PMID- 9542225
TI  - [Mortality rates in childhood and their causes in Spain. 1991].
AB  - OBJECTIVE: The purpose of this study is to present the different pediatric
      mortality rates in Spain during 1991 and to describe the groups of mortality
      causes for the different ages in relationship to these rates. PATIENTS AND
      METHODS: We have used data from the National Institute of Statistics for the year
      studied. These data were summarized, grouped and simplified. In order to clarify
      them, causes of death have been expressed in percentage. RESULTS: The different
      mortality rates were: Infant mortality 7.19; neonatal mortality 4.57; early
      neonatal mortality rate 3.32; late neonatal mortality rate 1.25; postneonatal
      mortality 2.62; perinatal mortality 7.24; preschool mortality 1.75; mortality
      within the age group 5-9 years 1.26. For infantile, neonatal, early neonatal,
      late neonatal and postneonatal mortality the biggest percentage was due to causes
      depending upon congenital malformations and perinatal diseases. For preschool and
      school mortality accidents and tumors were the most frequent causes of death,
      although causes related to congenital anomalies were also responsible for a large
      percentage of deaths. CONCLUSIONS: Pediatric mortality rates in our country are
      more than acceptable and their causes are similar to those of other civilized
      countries.

PMID- 9542227
TI  - [The transmission of brucellosis via breast feeding. A report of 2 cases].

PMID- 9542228
TI  - [Herpes zoster during chickenpox].

PMID- 9542226
TI  - [Children with limb reductions in a population of 25,193 malformed newborns: the
      recognized causes. ECEMC. The Spanish Collaborative Study of Congenital
      Malformations].
AB  - OBJECTIVE: The purposes of this study were to analyze the causes of limb
      reduction deficiencies based on a clinical-epidemiological approach and to study
      the causes by clinical presentation. PATIENTS AND METHODS: We have used the data
      from the Spanish Collaborative Study of Congenital Malformations (ECEMC) during
      the period from 1976 to 1996, which corresponded to more than 1,300,000 births.
      Among these, we identified 851 liver-born and 40 stillborn infants with limb
      reduction defects. RESULTS: We could identify the cause in 177 (19.87%) of the
      891 cases with limb reduction defects. In the analysis by clinical presentation,
      in 52.19% of the cases the limb deficiencies were the only defect present in the
      children (isolated), 30.75% presented multiple congenital anomaly patterns, and
      17.06% were syndromes. The most frequent etiology was the genetic one.
      CONCLUSIONS: First, most of infants with limb deficiencies have unknown cause and
      these defects are most frequently isolated malformations. On the other hand, the
      results of this analysis permitted the following considerations in relation to
      the guidance for the diagnosis of infants with limb reduction defects. If the
      child presents with multiple congenital anomalies (multiply malformed infant) a
      chromosomal analysis should be performed and it should be determined if the
      infant was prenatally exposed to a teratogenic agent. If these two aspects are
      normal, we should clinically analyze if the infant could have a known syndrome.
      In addition, since in our data 10.32% of isolated cases were due to autosomal
      dominant genes, a detailed clinical analysis of close relatives should be done to
      determine if some of them present mild limb deficiencies in order to provide an
      adequate information to the family.

PMID- 9542229
TI  - [An immature gastric teratoma].

PMID- 9542230
TI  - [G-CSF treatment in a case of Kostmann's infantile congenital neutropenia].

PMID- 9542231
TI  - [A multiple rhabdoid tumor in a nursing infant: an unusual case in pediatrics].

PMID- 9542232
TI  - [Acute hemorrhagic edema in a nursing infant: a report of 5 cases].

PMID- 9542233
TI  - [A gastric trichobezoar].

PMID- 9542234
TI  - [Acute pain, analgesia and sedation in the child (I): its detection and
      evaluation].

PMID- 9542235
TI  - [Treatment protocol for juvenile tuberculosis. Sociedad Espanola de Neumologia
      Pediatrica. Juvenile Tuberculosis Working Group].

PMID- 9542236
TI  - [The antimeningococcal vaccination campaign in Cantabria, February-March 1997].

PMID- 9542237
TI  - [Heart catheterization and Kawasaki disease].

PMID- 9542238
TI  - [Cardiopulmonary resuscitation in pediatrics. A method for automating the dosage
      and procedures].

PMID- 9542239
TI  - [Scrotal involvement in Schonlein-Henoch purpura].

PMID- 9542240
TI  - [Measles. A disease of childhood that is shifting to adolescence].

PMID- 9542241
TI  - [Subepithelial glands in the hamster's larynx].
AB  - We have performed, with light microscope, a study about the distribution and
      morphology of the subepithelial glands of the hamster's larynx. The results are:
      at the base of the tongue the great deal of the glands are mucous, at the
      epiglottic base seromucous and at the subglottic space (at the level of cricoid
      cartilage) serous.

PMID- 9542243
TI  - [Neurilemmoma of the external ear].

PMID- 9542242
TI  - [Histological study of the rat's nasal sinus cavity. Its use in investigation].
AB  - An histologic study was performed by light microscopy of the rat nasal cavity. A
      neuroepithelial lining is found in the backside of the cavity and the medial
      portion of vomeronasal organ. A respiratory seudostratified epithel with a great
      deal of submucous glandulae cover the remainder of the cavity.

PMID- 9542244
TI  - [Mast cells in the nasal mucosa of patients with nasal polyps. A histological
      study with lectins].
AB  - Histochemical studies done with lectins are helpful for differentiate between
      several carbohydrates and glycoproteins of cell structures. Mast cells
      predominate in the nasal polyps mucosa of these patients. Cytoplasmic granules of
      mastocyts reacted to all lectins employed but LTA.

PMID- 9542245
TI  - [Meningoencephalocele. A report of 6 cases].
AB  - The paper deals with the study of 6 patients having this malformation. Four were
      nasofrontal, 1 nasoethmoidal and 1 occipital cases. The last associated to
      harelip and cleft palate. Two of them exhibited neurologic deficiency. All
      underwent surgery, 3 in two steps, through intracranial approach and section of
      the encephalic segment, followed by osteoplasty from iliac crest for replacement
      the flawed piece of cranial bone. Afterwards straight aesthetic reconstruction.
      As etiological causation is accepted the parents multifactorial action of
      nutritional imbalance, tobacconism and the effect of weed-killers--so much
      employed in our country--which set in motion, all of them, the output of free
      radicals acting upon DNA of germinative cells. In this way is breacked the H
      bonds, determining the congenital malformations on the offspring. Diabetes and
      dipsomania are rejected.

PMID- 9542246
TI  - [Differences between excretory ducts of normal submucous glands and those of
      nasal polyps. A histochemical study with lectins].
AB  - We have performed an histochemical study with lectins of normal nasal mucosa in 6
      patients admitted at Hospital because an abdominal pathology, and other 6 with
      nasal polyps. Results showed a similar reactivity to lectins of excretory duct
      cells of seromucous glandulae of basement membrane of normal nasal mucosa and the
      analogous cells of the nasal polyps mucosa.